Human Growth Hormone NYC

I apologize for the quality of this image but hopefully its just clear enough for you to make out this week’s Genetic Engineering News poll. If you’re reading this in realtime you will see on GEN’s homepage.

In case you can’t read it, the poll is this:

“Which type of stem cells will be the first to move from the laboratory into clinical testing?

• embryonic stem cells
• induced pluripotent stem cells
• adult stem cells
• none of the above
• undecided”
  

The introduction to the poll is as follows:

“The 2009 Lasker Awards honored two scientists who developed nuclear reprogramming, a process that instructs specialized adult cells to form pluripotent stem cells. This has been widely hailed in the life science research community and the biotech/biopharma industry as one of the most significant findings of the past decade. While embryonic stem cell research has been plagued by ethical concerns, some believe that the newfound ability to induce pluripotency in adult stem cells will lead to breakthroughs in the therapeutic applications of stem cells. So we want to know which type of stem cells you think will win the race.”

C’mon GEN, are you serious? If you honestly missed the point that adult stem cells are already in clinical testing and use, then shame on you. If you’re trying to catch people in their own ignorance by this trick question then I suppose that’s a little more tolerable but a poll like this still perpetuates the misinformation – at least until you do everything you can to expose it.

This kind of misunderstanding about the true status of the development of cell therapies is pervasive. Late last year I commented on an article by Tom Feilden on BBC’s website in which he said things like,

• “…a sizeable number of exciting stem cell projects are now reaching the stage where they should be moving on from the research lab and into clinical trials” and
  
• “Regenerative medicine may finally be moving out of the lab and into the clinic.”

As we all know, stem cell research moved from the lab into clinical use decades ago (with stem cell transplantation) and there are now literally hundreds of clinical trials currently underway testing the use of different kinds of stem cell products for almost every imaginable condition not the least of which is Osiris’ Prochymal which has been tested now in two phase III clinical trials.

Perhaps the educated readers of this blog will think that it is not possible that readers of GEN could believe that adult stem cells are not already in clinical testing. Let me assure you there is a lot of misinformation about the maturity of the cell therapy sector even among those in biotechnology. As proof, a click on “View Results” shows that as of today the poll stands almost neck-and-neck. A mere 48.6% of respondents believe adult stem cells will beat ESC or iPS cells to clinical testing. 45.7% believe either ESC or iPS cells will beat adult stem cells into clinical trial.

What more can I say? We – you and I – must continue to do everything we can to raise awareness about the true status of the cell therapy industry and the products we are developing – even among our biotech colleagues.

–Lee

p.s. I know my Cell Therapy Industry HiLites has disappeared this summer. I’m doing everything I can do resurrect it from among the rubble left by summer holidays, home renos, new baby, and more work from clients than I could have ever expected.

www.celltherapyblog.com hosted by www.celltherapygroup.com

Last week I mentioned the Regenerative Medicine Foundation and the conference they have announced for Spring 2010. I promised to find out more and bring you what I learned.

I’ve discovered that the driver behind the RMF is Anthony Atala and Case Western. It is a 501(c)(3) charity, non-profit organization. It was formed in 2005 by Dr. Atala to host a meeting with the U.S. Food and Drug Administration (FDA) around the topic of regenerative medicine. In 2006, the Foundation was instrumental in the formation of STRAC, the Soldier Treatment and Rengeneration Consortium, a national partnership of leading military and academic research centers and industry. STRAC formed the basis for the Armed Forces Institute of Regenerative Medicine (AFIRM).

Now the Foundation announced the first annual “Translational Issues in Regenerative Medicine” Conference, to be held in Winston-Salem, NC, December 8-10. The conference promises to focus on best practices in clinical trials and GMP facilities, as well providing a forum to discuss regulatory and reimbursement challenges. In addition, the conference will feature a venture forum to introduce early-stage and later-stage companies to accredited and institutional investors.

As its name suggests, the organization functions like a “foundation” rather than a member-based organization. This is reinforced by the fact the “Participate” page on the website has no content.

All of this is interesting but nothing more than you would learn from the RMF’s website. What I DID discover this week that isn’t obvious from anything yet online is that Atala has also been a primary driver behind the creation of a newly announced organization, this one a 501(c)(4) organization intended to be much more about lobbying.

This week the Alliance for Regenerative Medicine was formerly launched. (no website yet). Headquartered in Washington, DC, the Alliance is “dedicated to promoting regulatory, research, and reimbursement policies that will foster innovation in regenerative medicine” in addition to serving as a “source of information about regenerative medicine for policy makers, the media, and the general public”.

With Atala’s ‘encouragement’, Michael Wener of DC law firm Holland & Knight and Morrie Ruffin of Adjuvant Global Advisors signed up to be the driving force in the creation and evelopment of the Alliance intented to bring together academic institutions, non-profit organziations, and companies that commit to supporting and participating in a lobbying organization to promote much-needed policies in support of the regenerative medicine sector.

The organization intends to announce its final list of charter members later this month. Thus far its a respectable list including Wake Forest Institute for Regenerative Medicine, Stanford University, the University of Washington, Georgia Tech University, the Genetics Policy Institute, Geron, Johnson & Johnson, Aldagen, iZumi, Fate Therapeutics, Maxcyte, Kleiner, Perkins, Caufield and Byers, and Proteus Ventures.

Werner and Ruffin both have a great deal of experience with Capitol Hill and the biotechnology sector. I had a great conversation with Werner this week and am very encouraged by the plans for the Alliance and their intended inclusiveness. In my opinion, the Alliance promises to fill a much-needed gap unmet by any existing organizations. I will dedicate a post to more information about the Alliance in the days to come.

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More stakeholders united in one place at one time than any other.

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FINANCIAL

Here’s the cool part: Check out their product animation on YouTube.

CLINICAL

Ok, this isn’t exactly a clinical story but it’s the closest thing I’ve got this week and I hate leaving sections bare.

Geron Corporation (Nasdaq: GERN) has published in advance of print in the journal Regenerative Medicine a paper that reports that dendritic cells (DCs) scalably manufactured from human embryonic stem cells (hESCs) exhibit normal functions of naturally occurring human DCs found in the bloodstream. This, they say, supports their planned use of hESC-derived DCs in their therapeutic vaccine currently in Phased II for AML but employing autologous dendritic cells. (see GEN’s summary here)

COMMERCIAL

The big deal of the week, of course, was between GE Healthcare, a unit of General Electric Company (NYSE: GE), and Geron Corporation (Nasdaq: GERN).

The companies announced an agreement to co-develop human embryonic stem cell (hESC)-derived assay products for in vitro drug screening with the aim of having products on the market in by “early 2010″.

Under the worldwide, exclusive license and collaboration agreement, GE Healthcare obtained an exclusive license to Geron’s hESC IP and a sublicense under Geron’s rights to foundation hESC patients held by the Wisconsin Alumni Research Foundation. IP arising from the alliance will be shared between the companies, with GE Healthcare retaining rights to the resulting technologies for drug discovery applications and Geron for cell therapy applications.

When Geron announced that its IND had been accepted by the FDA earlier this year, Okarma made quite a bit about how they had figured out how to scale the production of their product ” unlike adult stem cell therapies” and that their product was “scalable in the same way as a monoclonal antibody”.

This theme continues in this announcement with Geron’s David Earp saying ““Geron is intensely focused on developing hESC-based cell therapies, and the expertise that we have developed in scalable manufacturing and differentiation of hESCs to specific cell types is directly applicable to the production of these dells for drug discovery.”

Interestingly, GE claims it is bringing “expertise in cell manufacturing” to the deal. GE Healthcare will fund the R&D program and will be responsible for manufacturing, sales and distribution of products developed under the agreement.

Click here for more background information

As has been discussed here several times, ever since Cell Genesys Inc (NASDAQ: CEGE) pulled the plug on its late-stage trials of its GVAX immunotherapy triggering Takeda Pharmaceuticals to pull out of its co-development deal for the product, Cell Genesys has been busy dealing with downsizing, lawsuits, and shopping itself around to potential suitors looking primarily to take it on for its cash.

This week BioSante Pharmaceuticals, Inc. (NASDAQ: BPAX) anted up to announce it is merging with Cell Genesys in an all-stock transaction valued at about $38 million – pretty much the exact amount of cash CEGE has in its bank account. the surviving entity will be BioSante.

Cash value is actually a generous purchase price for biotech companies which usually come with a burn rate that makes then worth less than their cash. CEGE, however has no clinical program, had sold most of its assets, and had downsized to 9 staff in a rented office.

There are, of course, persistent rumors of back alley shenanigans that took place in CEGE’s demise but we’ll leave these on the street. What is interesting to me is that BioSante has suggested they will examine options for the future of Cell Genesys’ GVAX Immunotherapies, including potential combination with BioVant, BioSante’s vaccine adjuvant, as well as possible external collaborations. The combined entity is also on record saying they will try to outlicense other Cell Genesys technologies.

GEN this week carries an interesting article on a company applying its existing technology to cell therapy bioprocessing scale-up. The article sites “…large-scale culturing of embryonic and induced pluripotent stem (ES, iPS) cell lines for use in regenerative medicine and drug discovery applications” as still a “major challenge” for the industry. Cyntellect, Inc. reports that its Stem Cell Manager “is a series of stem cell management processes including automated physical passage of stem cells, automated embryoid body generation, and purification of specialized cell types derived from stem cells” which can help alleviate some of the major challenges in large-scale automation of the processes required to manipulate sensitive therapeutic cells.

MISCELLANIA

ProChon Biotech, Ltd., a company working with tissue regenerative technologies announced that it recently received the Genzyme Award for Excellence in Cartilage Research for its poster presentation entitled, “Comparative Analysis of Cell Sources for Cartilage Cell Therapy.” The company reports that the research recognized by the award is incorporated into their development pipeline and will compliment its BioCart™ Cartilage Regeneration System.

Prochon’s BioCart^™ Cartilage Regeneration System is an autologous chondrocyte implant system that – and here’s why I love this story because this is just another example of a commercially-available cell therapy that people in the US never talk about – is commercially available in Italy, Greece and Israel and is undergoing an FDA Phase II multicenter clinical study in the United States. The company reports that to-date over 70 patients have received the BioCart^TM implant with some patients over five years post-implantation.

I came across a nice piece this week discussing Arteriocyte Medical Systems‘ work on its DARPA-funded project to create human blood from stem cells at a rate that could allow the military and hospitals to produce units of blood on site. The company claims that with a technology developed by a company called Nanex, they are able to grow stem cells at a rate 10 to 100 times faster than with more traditional methods. The Nanex technology mimics a bone marrow environment in which stem cells can grow quickly. The trick now is to automate and scale-up the system to meet the specs DARPA required in its project paramaters.

Sign-off

The latest issue of the journal Regenerative Medicine has been released and it looks well worth the read. Here the table of contents.

Hope this was useful.

www.celltherapyblog.com hosted by www.celltherapygroup.com

I don’t have much time to give you an extensive blog about the issue but I did want to bring this to your attention. Here’s the nutshell.

The NIH’s SBIR (Small Business Innovation Research Program) funding mechanism has been an important one for small businesses who are not big/mature/saavy/desperate-enough to land venture capital funding, have very limited access to other NIH funding, and have tapped out the available angel/seed/friends_n_family resources at their disposal.

Since 2003, one of the hallmarks of the rather small SBIR funding pot ($2.2 billion a year) has been that it was not available to companies that are majority-backed by venture capital. Before 2003, venture-backed firms were allowed to participate in the SBIR program.

The program is scheduled to expire next month and so is up for renewal. The House committee responsible for the program has proposed that the VC-restriction be removed thus re-opening the program to a whole slew of companies previously ineligible. The House just passed this bill. A senate version of the bill tries to reach a compromise by limiting the amount available to venture-backed firms.

Whatever your opinion on the judiciousness of this move, there is no doubt that opening up eligibility to the program will dilute the available funding.

Here is a link to yesterday’s article on the subject in the Washington Post.

Fellow blogger Steven S. Clark (BioScience Biz) has a just posted his most recent update and opinion on the matter that is well worth the read.

www.celltherapyblog.com hosted by www.celltherapygroup.com

As Late, Late Show host, Craig Ferguson, says…”It’s a great day for America. ‘Why is it a great day for America,’ you ask? Well, let me tell you”.

The US House of Representatives has passed what promises to be (if approved by the Senate) the largest single budget increase for the FDA in the agency’s history. Now many an economist or financial wizard may argue why this is fiscally irresponsible given America’s economic woes but it certainly is promising for the biotech industry which has suffered due to a lack of resources in the Agency overseeing the sector. This lack of resources permeates into almost every interaction with the agency whether it be awaiting new Guidance, submission reviews, staff attrition, etc.

As it happens it is also a great day for the mother country from which America declared its independence because of their dastardly tea-taxing ways. “Oh, why ever it that so?”, you might ask with a fake English accent. Well I’lltell you. It’s because the UK Office for Life Sciences (OLS) has announced a “Life Sciences Blueprint” that will attempt to capitalise (well, that’s how the English spell it) fully on its “leading global position in regenerative medicine”. The OLS has announced £18 million funding from the Technology Strategy Board for a Regenerative Medicine programme (again with the English spelling) of investment to support key areas of commercial R&D and the development of R&D partnerships, supported by additional funding of £3.5 million from the Medical Research Council, the Engineering and Physical Sciences Research Council and the Biotechnology and Biological Sciences Research Council.
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I fell in love with this conference, the venue, and the charming city of Leipzig when it was held in 2007. For a unique and international take on the multi-disciplinary world of regenerative medicine, you should consider meeting at the WCRM 29-31 October 2009.

www.wcrm-leipzig.com

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Well I seem to be on a roll with anything related to Wake Forest recently so ‘why stop now’ I ask myself, without any compelling reply to the negative. This is just a little FYI. The Babcock Demon Incubator (BDI), a new venture incubator at WFU, promises to be a unique new venture incubator opportunity for regenerative medicine startups. The BDI has has fully equipped wet lab space with available equipment including chemical and tissue culture hoods, PCR, Gel systems, HPLC, microscopes, centrifuges, etc. In addition, BDI clients have access to collaborative opportunities at the Wake Forest Institute of Regenerative Medicine and to a wide range of services and specialized equipment. The incubator provides both residential and non-residential client models depending on client needs. All clients have access to office or lab space, can take advantage of business consulting, and access to an extensive services network designed to provide difficult-to-obtain resources to help young companies succeed. For more information, visit the BDI web site.

As regular readers of my Industry HiLites will know, from time-to-time I occasionally profile a company here in the front-end of the post providing some background, analysis, and recent developments. I’ll formalize this a little by calling it a COMPANY PROFILE but won’t promise to include one every time.

On another house-keeping matter you will note that I’ve changed the section title “FINANCIAL” to “FINANCIAL and DEALS”.

COMPANY PROFILE

Bioheart, Inc., (OTC Bulletin Board: BHRT) has announced that they will proceed to the final phase of their clinical trial with muscle stem cells for treatment of cardiovascular disease.

The company convened a panel of experts to review pre-clinical data dating back to 1988 and clinical data from controlled studies which began in early 2000 (involving nearly 400 patients). Bioheart’s latest Phase II/III MARVEL study has undergone interim analysis. While the data has not been disclosed pending publication confidentiality, this panel of experts was reportedly asked to also review this data.

The panel is reported to have “unanimously and enthusiastically endorsed moving forward” to complete the final phase of clinical trials (MARVEL) to advance muscle stem cell (myoblast) therapy for treating heart failure with the goal of bringing the product to market with FDA approval and CMS reimbursement.

It’s not entirely clear to me how or why this panel of experts was called together but a listen of the audio of the panel discussion frankly makes it sound a little bit like a love-in for Bioheart. In the accompanying slide deck, you will find an overview by Chairman and CEO, Howard J. Leonhardt listing an extremely aggressive list of deliverables for 2009 for a dizzying array of clinical products & programs.

On the financial front, Leonhardt states the company has to-date invested $125 million to support heart failure-related research – $85 million of which was in paid capital.

From its May 20, 2009 Form 10-Q Quarterly Report filed with the SEC, “The Company has incurred significant operating losses over the past several years and has a deficit accumulated during the development stage of $98.6 million as of March 31, 2009. In addition, as of March 31, 2009, the Company’s current liabilities exceed current assets by $12.7 million. Current liabilities include notes payable of $5.4 million. …the Company also has an obligation of $3 million to the Company’s Chairman and spouse [they repaid the principal on a company loan and a pro rata portion of accrued interest ]. The Company does not have sufficient cash to support its operations through December 2009. The Company will need to secure significant additional sources of capital in June 2009 to develop its business and product candidates as planned.”

On July 9, the company issued a press release saying that between October 1, 2008, and July 7, 2009, Bioheart received proceeds in the amount of $2,855,830 from the placement of restricted common stock and warrants under its current offering which it has now extended through October 2009. There’s a little positive spinning here because this would appear to include the approximately $1.8 million raised in the sale of stocks and warrants which it announced back in October 2008. The new ~$1M appears to be coming in dribs and drabs from the sale of small chunks of stock or warrants including, if I’m reading it right, the granting of stock in repayment of an outstanding loan (see the May 2009 Quarterly Report for clarification and details).

FINANCIAL and DEALS

Bioheart, Inc., (OTCBB: BHRT) has raised approximately $1 million over the past few month in an ongoing offering (see details above).

Aastrom Biosciences, Inc. (Nasdaq:ASTM) has gained a modest extension from NASDAQ to comply with the $1.00 minimum closing bid price rule in order to remain listed on the Nasdaq Capital Market. This means they now have until October 1, 2009 to regain compliance by achieving a $1.00 closing bid price for a minimum of 10 consecutive trading days anytime before that date. If not, they get kicked off the NASDAQ and forced to find another market for their listing. Absent a stock split it seems an unlikely goal give that the stock is currently trading in the region of .35 cents and the 52 range for the stock is 0.15 – 0.78.

Quantum Immunologics, Inc, a Tampa, Florida company focusing on the research and development of cancer immunotherapies, announced that the first patient in its breast cancer trial has begun to receive its dendritic cell therapy. QI is currently sponsoring and conducting an FDA-authorized Phase I/II clinical trial testing the safety and efficacy of its immunotherapy on 27 Stage IV breast cancer patients who have failed conventional therapy. Each patient will receive three monthly injections of the patient’s own dendritic cells that have been sensitized to OFA (oncofetal antigen) – a cancer antigen (a protein found on cancer cells that can be targeted by the body’s own immune system) found in many tumor cell lines or fetal tissue, but absent on normal, healthy tissue. When the sensitized cells are injected back into the patient, QI expects the patient’s T-cells will locate the OFA found on the patient’s cancer cells, thereby generating an immune response with the goal of killing the cancer cells and preventing further spread of the disease.

Harvest Technologies Corp. announced that the company-sponsored 60-patient clinical trial conducted in Chennai, India using the company’s BMAC point-of-care System to treat patients with non-reconstructable Critical Limb Ischemia (CLI) has completed enrollment. Over 300 CLI patients have been treated with the Harvest BMAC treatment protocol in an ongoing multi-center FDA study in the U.S. and other studies in India, Germany and the Czech Republic.

COMMERCIAL

Dendreon Inc (NASDAQ:DNDN) is currently eying Atlanta, GA as the location for a new $80 million, 300-person manufacturing facility. “Why Atlanta”, you ask? “Ah, good question”, I say. It all comes down to transportation logistics. An autologous cell therapy like Provenge requires the acquisition of a biological sample from the patient which is then used to manufacture a unit of the therapeutic that is then shipped back to the patient’s clinical stie for administration. This makes logistics a primary consideration for the business model. Atlanta, has one of the world’s busiest and most connected airports.

Cord Blood America, Inc. (OTCBB:CBAI) has signed a lease for a 17,000 square foot building in Las Vegas, Nevada, for a state-of-the-art laboratory for the storage of multiple stem cell products including umbilical cord blood stem cells. Aggressively the company intents to start processing and storing its customer’s umbilical cord blood stem cells in the facility in the fourth quarter of 2009. According the the company CEO, in 2010, CBAI intends to expand its cryogenic storage services to other forms of stem cells, including peripheral blood stem cell and adipose tissues. Presumably this move to self-manufacture will mean that its Corcell banking brand will no longer be able to claim the advantage of cGMP-quality processing and storage which it has made a part of its pitch since contracting with Progenitor Cell Therapy in 2007.

Meanwhile CBAI has picked the pockets of Bio-Matrix Scientific Group Inc (OTCBB:BMSN) by hiring its former Vice President and Chief Operating Officer Geoffrey John O’Neill as its new Laboratory Director and Brian Pockett as Vice President of Laboratory Operations.

Meanwhile in a weird twist of almost Seinfeld-like interconnectedness, in researching SEC filings for this post I discovered that on August 11, 2008, MSN entered into a Letter of Intent with CBAI regarding the processing and storage by BMSN of cord blood specimens newly acquired by CBAI for consideration acceptable to BMSN. It would appear, however, that deal never materialized given CBAI’s recent moves.

Living Cell Technologies Limited (ASX:LCT; OTCQX:LVCLY) has announced the formation of a subsidiary, LCT Biomedical Limited in Russia, to facilitate the commercial development of DIABECELL®, its lead product for the treatment of type 1 diabetes. Reportedly the regulatory process has already been initiated and it is envisaged that the pivotal study and product would be registrable by late 2011. They recently implanted their 8th patients with DIABECELL, their porcine xenogeneic cell therapy product in clinical trial for type 1 diabetes. The plan is for the product to be manufactured and supplied from New Zealand, where the company is located, for the foreseeable future.

Progenitor Cell Therapy, LLC has appointed a Vice President of Manufacturing Operations with extensive pharmaceutical production experience to head its two U.S. contract manufacturing facilities. PCT recent announced the recent appointment of Daryl LeSueur as Vice President of Manufacturing Operations. As head of Manufacturing Operations, Daryl is responsible for managing and supervising the day-to-day conduct of the manufacturing, packaging, and operational functions of PCT’s two North American contract manufacturing facilities.

MISCELLANIA

The ERA Consulting Group is proud to announce the next intERActions seminars entitled:

The Regulation of “Advanced Therapy Medicinal Products*” in Europe, from the Clinic to Approval (*Cell Therapy, Gene Therapy and Tissue Engineered Products)

Topics to be covered:
* The EU regulatory framework for Advanced Therapy Medicinal Products (gene, cell therapy and tissue engineered products)
* Opportunities in the EU regulatory landscape, especially for rare diseases: How can they benefit your company?
* Current and future regulatory guidelines: Latest developments and implications for your company and product portfolio
* What are the EU CMC/quality issues/requirements at various stages of development?
* Preclinical development program: EU regulatory expectations – rational approach
* Clinical trials with Advanced Therapy Medicinal Products in the EU

Including Europe in your Strategy to Add Value to Early-Stage Biotech Product Development

Topics to be covered:
* The value of including an EU component into your overall regulatory strategy
* Optimizing interactions with European regulators and how this can aid development and add value
* The benefits of orphan medical product designation in the EU and an explanation of the procedure
* Clinical Development in the EU: The European Clinical Trials Directive
* Opportunities in the EU regulatory framework to add value and reduce time to approval, such as accelerated review, conditional approval or exceptional circumstances
* Compassionate use programs

The seminars will be held at The GreenV Sustainable Center of South San Francisco on 14th – 15th September 2009. For a complete program and registration information, please visit their website at: www.eraconsulting.com.

After 15 years in the biotech conference industry, the Williamsburg BioProcessing Foundation has shuttered its operation in financial distress. Hasta la vista, Wilbio.

Sign-off

Ok, this is a stretch for inclusion in this blog which is why I leave it to this humble location in the post but two fellow Canadians have been named among the six researchers to receive prestigious awards from the American Society of Hematology later this year. Congratulations to stem cell researchers Connie Eaves and John Dick.

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www.celltherapyblog.com hosted by www.celltherapygroup.com

I’m always skeptical of companies or products or technologies that depend on a ‘paradigm-shift’ or ’sea-change’ in the long-entrenched habits of people before they will be widely adopted and/or successful.

It’s why, for example alternative fuel autos might succeed in the U.S. where public transit has not – because they don’t require as big a change. People can stay in their car and change their habits less.

Disruptive Technologies Lead to Paradigm Shifts

Nevertheless there are from time-to-time disruptive technologies that do arise which are paradigm-shifting. These are readily (though perhaps not quickly) adopted because the benefits are seen to outweigh the trade-offs and/or effort required to make the change. In many instances there are entire industries built around the pre-existing technologies that foolishly resist such change rather than learn to adopt and adapt. It’s the classic mistake of railway companies believing they were in the business of trains rather than transporting people and goods and thus missing the opportunity to dominate transport by road and plane when these industries started to compete for the transport customer.

Will Cell Therapies Disrupt Sufficiently to Shift the Therapeutics Paradigm?

There are a lot of people talking about how regenerative medicine, personalized medicine, and cell therapies are going to revolutionize health care. I’m one of them. There are, however, many good reasons to be skeptical – not the least of which is the sheer size of the industries built around the pharmaceutical model and the power they can exert in resisting change. This might be comparable to Detroit’s resistance to alternative transport systems or Houston’s resistance to the use of fossil-fuels. It’s massive.

But just as Detroit is now embracing the need for change and Houston is touting alternative energies, could it be that New Jersey is having its own ‘come-to-Jesus’ moment and realizing there may be – perhaps must be – a future for pharma beyond the blockbuster pill model? The other big ‘industry’ to convince is the healthcare inudstry. How readily will hospitals and doctors adapt to a therapeutics paradigm shift?

Last week, I had an interesting conversation with someone from a struggling cell therapy company that has completed a semi-successful phase II trial and is very quickly running out of money despite having been on a road show for over a year. They are engaged in a “number” of “partnering” discussions with pharma companies who understand the science, the manufacturing, and the cost-of-goods data but say they are still uncomfortable with the “business model for cell therapy.”

The know the market, have good data on the COGs and can assume a certain product price and reimbursement…so what’s left? I’m told that “business model” is code – at least in this instance – for two concerns:

(1) what will clinical adoption rates be like, i.e., will doctors adopt these new therapies and, if so, at what rate? and
(2) the model they are being presented does not offer them the type of margins they’ve come to expect.

Let’s look at each of these in turn.

Health 2.0

Doctors have traditionally been driven by clinical results and reimbursement. But there’s a new driver in town – it’s the informed patient and their participation in Health 2.0. Patients no longer rely solely on their physician for healthcare information.

Deputy Editor of Wired magazine, Thomas Goetz, author of “The Decision Tree” (blog and upcoming book), describes this new era of healthcare as follows:

“We are entering a Third Phase of medicine – one that spots disease and illness based on risks rather than one that responds to symptoms (phase 1, from pre-history to the mid 19th c), or one that seeks out the causes (phase 2, from circa-1850 to just about now).

These three phases closely parallel our technological capacity to spot disease: Phase 1 was primed to spot symptoms because humans relied on our senses – and nothing more – to recognize illness. If we couldn’t see it (or smell it), it wasn’t yet evident. Phase 2 emerged with the perfection of the microscope and the discovery of the germ theory of disease: finally we could see disease in its pathogenic form – bacteria, mostly – and thus began a race to find the little buggers that were causing disease. The late 19th century saw a flurry of diagnosis, as the cause of one disease after another was identified, and the Pasteurs and Kochs went about devising antibodies or vaccines to vanquish them… So now this third phase dovetails with the bevy of new diagnostics emerging – devices and techniques that look for certain molecules and DNA strands to not only detect the presence of disease, but predispositions towards certain conditions as well…

This third phase contains elements of what many are calling “personalized medicine,” but I hate that term – it sounds too servicey and implies that this is simply regular medicine/clinical practice that’s been tailored for you, as if we have a computer watching our health (it’s “personalized!”).

To my mind, what’s happening now is much more than simply a move to personalization; it’s an entirely new way of relating to disease and illness, one that’s as impactful and as new as the realization that germs – not bad air or bad luck – caused disease. What’s happening now makes disease/illness an optional state, one that can be opted out of (ideally) or engineered against (more likely).”

This is, he says, “…a new phase of health and medical care, where more decisions are being made by individuals on their own behalf, rather than by physicians, and that, furthermore, these decisions are being informed by new tools based on statistics, data, and predictions. This is a good thing – it will let us, the general public, live better, happier, and even longer lives. But it will require us to be stewards of our health in ways we may not be prepared for. We will act on the basis of risk factors and predictive scores, rather than on conventional wisdom and doctors recommendations.

We will act in collaboration with others, drawing on collective experience with health and disease, rather than in the isolation and ignorance that can come with “privacy” concerns. And we will act early, well before symptoms appear, opting to tap the science of genomics and proteomics in order to mitigate our risks down the road.

Together, these tools will create a new opportunity and a new responsibility for people to act – to make health decisions well before they become patients. This can be characterized as a decision tree, a series of informed choices we will make to minimize uncertainty and optimize our outcomes. Indeed, we will use decision trees to navigate most of our health decisions, sometimes in overt ways – new decision support tools will both inform us and guide us, and they’ll be steeped in statistics, prediction, and the power of collective experience.”

For better or for worse, patients have an increasing multitude of sources and options. Not only are patients now much more informed of their diagnoses and conditions but also of their treatment alternatives. More each year are demonstrating a willingness to access cell-based treatments out-of-country. Others are lobbying for the loosening of the regulatory sphincter around cell-based therapies such as stem cell transplantation, Dendreon’s PROVENGE, etc.

Increasingly patients’ demands are influencing doctors as much or more than anything else. Pricewaterhouse Coopers recently listed “the internet and social network” as the Health Industry’s “top nine issues for 2009” citing web2.0 as “changing how healthcare is navigated and experienced by consumers”.

It remains to be seen how doctors will adopt cell therapies and this will depend in large part on the adequacy of reimbursement but certainly patients are driving their doctor’s decisions like never before and patients seem enthused – perhaps even overly so – about cell-based therapies.

Therapeutic Profit Margins

In terms of margins, even pharma executives are now realizing – in the face of diminishing pipelines and massive R&D costs per drug – that the models that have worked so well to-date financed by the kinds of margins they have received to-date may not be possible going forward. M&A, the creation of decentralized divisions, increased academic collaborations, etc…. they are all measures to try and address the same problem of diminishing margins.

Decreasing product margins are being tackled like it’s the disease when at least some would suggest it’s the symptom. The disease may not be lower margins at all but the model which demands such massive margins to succeed. But more on that in just a minute…

Personalized Medicine

I believe there is a third challenge to pharma’s “business model” concerns. From one direction we have pharma’s increasing desperation for new therapeutics; from another direction comes the public’s increasing demand for access to cell-based therapies, and – to complete the trifecta – we have the fast-growing sector(s) of personal genomics, theragnostics, and/or personalized medicine.

The ability to analyze the effects of therapeutics on patient sub-populations and use that to target such groups and/or tailor therapeutics accordingly opens up so many promises therapeutically but also puts incredible additional pressures on the blockbuster model with its low-rate of success per overall prescription rate. Some insurers are now catching on to the notion that reimbursement can be – perhaps should be – tied to therapeutic success and are willing to pay a higher price tag for success but nothing at all for failure.

Others before me have described the increasingly hard-to-ignore crack in the blockbuster model much better than I. One of the better analyses I’ve read recently can be read here.

To predict that cell-based therapies will contribute to and succeed because of a shift in the healthcare paradigm may not be that much of a stretch at all. The stars do appear to be aligning for a rather wholesale change to be readily adopted by all involved – or at least the major players.

…

(click here to continue to Part II)

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…this is a continuation of Part I…

So are Personalized Medicines the Long Tail of the Therapeutics Industry?

In 2006, Chris Anderson, Editor-in-Chief of Wired magazine, released “The Long Tail” – a book describing the Web 2.0-induced business-to-consumer economics (r)evolution enabling businesses to now deliver product at outrageously affordable prices to global micro-markets.[i] The book quickly became one of the most influential business books of the ‘new economy’.

Indeed this flat new world – as Thomas L. Friedman describes it[ii] – is all about micro-trends and micro-markets, empowering small companies and niche products to participate successfully in the marketplace along with Fortune 100 companies and blockbuster products. More than that, this paradigm shift is forcing product and service companies to revolutionize their business and pricing models, the latest and rabidly successful of which is the pricing model of “Free!”. The blockbuster-based business model that depends on the economics of a ‘hit’ (whether it’s a platinum-selling CD or a ‘blockbuster’ drug) is no longer seen to be the only way to make money and, indeed, may not have any future at all.

To date, this internet-driven Long Tail (r)evolution has had its largest impact on – if not been largely restricted to – the retail sector. Business-to-consumer (B2C) companies are now enabled like never before to profitably supply unique global products to meet customer demands. In this respect, the (r)evolution has had a visible impact on the retail side of the pharmaceutical and biotech industries. However the ongoing realization of “personalized products” as the future of medicine for consumers seems a perfect fit for the Long Tail economic model.

But does this apply to therapeutics?

To the extent that the Long Tail economy is less about the mass market and more about businesses succeeding in serving niche markets with unique and/or customized products, the analogy fits.

Certainly, it would appear the sun is setting on the “blockbuster hit” days of the therapeutics industry. In June 2008 Genentech’s Susan Desmond-Hellmann, president of product development, when outlining the biotech giant’s development strategy to a group at the Goldman Sachs healthcare conference, told the group that the blockbuster drugs of the past may never be duplicated. “Future drugs,” she stated, “will cater to a smaller, better defined group of patients” and “the days of big cholesterol-lowering drugs for millions of people may be behind us.” (link).

In a June 8, 2009 post, authors of the IN VIVO Blog stated that pharma “managers these days are learning to leverage only very modest top-line growth into faster bottom-line growth through cost-savings, bolt-on acquisitions, and rapid introductions of incrementally-improved new products. The traditional, high-risk, high-growth R&D-based model is gone, in case you hadn’t noticed.”

The second indication that personalized medicine fits with the Long Tail supply-demand model is that therapeutics can now be customized taking advantage of personalizing elements such as HLA-typing and advances in genetic, diagnostic, and discovery testing that will permit us to more effectively both pre-select which medicines are best suited for which patient sub-groups and develop therapies that are better suited to particular genetic groups. On the clinical end of the spectrum, advances in theragnostic tools and surrogate biomarkers (e.g., imaging) are allowing clinicians to much more rapidly assess personal responses to treatment and adjust their therapeutic regimines accordingly before any symptomtic response can be observed.

The ability to match therapeutics to genetic make-up, disease stage/presentation, or predisposition will allow the provision of treatments with more confidence in their expected efficacy, fewer patient-specific adverse reactions, and result in cost savings to the health care industry and a better return to fund the premium for the development of such products.

In a recent interview with Xconomy’s Luke Timmerman, Alan Frazier, founder and managing partner of Seattle-based Frazier Healthcare Ventures, one of the world’s biggest life sciences venture capital funds, said,

The trend is toward smart pharmaceuticals that address smaller populations, narrower indications, with better results. It’s based on a better understanding of disease from genomics and proteomics. You’ll see more targeted drug delivery. You’ll have incredibly focused pharmaceuticals, which will take care of some of the safety issues you read about.

Does the model apply to cell therapies?

At the intersection of the personalized and regenerative medicine sectors, lies the therapeutic industry’s response to (or reflection of) both the demand for and the ability to deliver a more personalized therapeutic to the consumer (the patient).

If the tail of the therapeutics market is being stretched longer to include products better targeted to smaller markets, this therapeutics Long Tail will almost certainly include regenerative medicine (regen 2.0) products and many of these will be cell-based therapies.

The cell therapy sector now encompasses the convergence of three distinct technologies, i.e. cell transplantation, tissue engineering, and biomaterials. Often also drawn in are elements of gene and molecular (e.g., proteins and antibodies) therapies.

Autologous cell therapies are the ultimate personalized medicine and while such medicines are often not included in definitions of personalized medicine, any approach to regenerative medicine – whether using tissue engineered products, cell-based therapies, small-molecule drugs, scaffolds, nano or biobots, etc – intended to trigger in vivo regeneration or repair… is personal!

Again, to the extent the Long Tail economy is about “selling less of more” then medicines such as cell therapies will certainly be part of the long tail of the therapeutics industry giving access to highly-personalized, tailored products to meet the unique needs of the consumer.

But does the Long Tail economic model apply?

While there may well be blockbuster cell therapies in the future, concern around the scarcity of potential blockbusters in cell therapy are seated in the notion that the blockbuster economy is the only successful model.

Who thought you could make money by giving free access to internet searches and email? There are a lot of ways the analogy breaks down but what the Long Tail economy has shown us is modern corporate ingenuity in finding profitable business models in niche markets despite the long-standing dominance of blockbuster products.

Where the paradigm falls short, in my opinion, is when one realizes that a fundamental pillar to the Long Tail economy is the commoditization of products and production processes as well as the standardization of delivery systems. The Long Tail economic model is enabled by the fact that the cost of goods sold has been brought sufficiently low enough – by new technologies which allow for small batches to be produced and shipped – that the products in question are affordable to most. Highly unique and/or customized goods were always available to those with sufficient ability to pay. The Long Tail brings these kinds of products to micro-market at the same price or lower than their mass-market counterparts.

We are a long way from this kind commoditization of personalized medicines and, in particular, of cell-based therapies. There is little-to-no standardization of production systems at any scale. The next generation of these therapies will still be highly priced goods which many people, insurers, and/or healthcare systems will be pressed to afford.

In once sense, this is not surprising. Even in the world of electronic or digial products, Moore’s principle only applies because the cost of goods for new technologies when they first enter the market are prohibiitively expensive. If the model applies in the therapeutics industry, technological advances in production will bring down the cost of goods and therfore the price.

On the other hand, what drives the price of therapeutics has not been so much the cost of goods (production) but the need to recoup massive upfront R&D costs which must be recovered (with a reasonable profit) during the life of a patent.

Will this change with personlized medicines and cell therapies? One could argue it might if personlized medicines and cell therapies can deliver on the promise to have a much higher effective rate among those given the therapies. Pharmaceuticals have a notoriously low effective rate among those prescribed any given drug. New research methodologies employing surrogate biomarkers, imaging, cell-based assays, etc promise the potential to significantly lower R&D costs by (a) getting to a much quicker “go/no-go” decision point in therapeutic development, and (b) identifiying patient sub-groups for which the therapeutic will have a high rate of effectiveness. One the one hand, this has the potential to lower the cost of goods (driven by R&D costs) and simultaneously justify a higher price point because of a high rate of therapeutic success.

However, even if we were able to materially lower upfront R&D costs, this still does not change the fact that cell therapies are costly to produce on a per-unit basis and the opportunity to “scale-up” is limited particlarly with autologous cell therapies which require lot sizes to be an individual batch. While this is a seperate discussion, I am confident technological and/or commercial innovation will find a way to economically bring therapeutics to market that are proven effective. I am not alone. Recenly Howard Liang, MBA, Ph.D., Analyst and Biotechnology Managing Direct at Leerink Swan as quoted as saying that “Autologous manufacturing is not the deal breaker it used to be. If these [cell-based] vaccines work for really difficult-to-treat diseases, the manufacturing issues will be worked out.” (”Special Report: Customized Cancer Vaccines Finally (Maybe) Arrive”. GEN News Highlights. 12 June 2009)

There are other reasons the Long Tail business model as it is currently defined does not fit cookie-cutter with the therapeutics industry not the least of which is that the consumer demand does not solely regulate supply. In highly regulated industries, the economies are different. Some would argue this should not be the case particularly if personalized medicines, genomics,theragnostics, etc advance to point where the consumer has an abundance of therapeutic information and options but that is the subject of another discussion.

In the end, it is certainly clear to me that the emerging technologies are enabling new therapeutic paradigms that will introduce elements of the Long Tail business model into the therapeutics industry.

How much Impact will Cell Therapies Have on New Therapeutic Paradigms and Systems?

Despite the exponential escalation of cell therapy innovation, is cell therapy ready to be a viable business that will make any material impact on the therapeutic industry? For reasons which I will continue to explore in this blog in the months to come, I believe the answer is ‘yes’.

The cell therapy industry has more products in late-stage development than many believe. While the existing commercial products are far from blockbusters and questions remain regarding the business models and potential margins for cell therapy products, ground-breaking research and market enthusiasm is driving a renewed interest among an early second-round of investors including participation by mature industry players making cautious plays in the sector. Regulatory issues in the primary markets of the US and EU are rapidly becoming less problematic though harmonization remains a significant challenge.

In blogs to come I will outline the commercial developments I see transpiring that make me believe the primary issues around the ‘business models’ question are being addressed. Regenerative and personalized medicines are enough of a force that creative business people will (a) invent ways to lower the cost of goods and (b) figure out how to price and reimburse appropriately to ensure effective therapies get to people that need them and incentivize doctors to prescribe them.

Most indicia point to this sector being poised for a phase that will start demonstrating real answers to those challenges which have to-date prevented many from participating in a sector that they believe presents too many unanswered risks.

Conclusion

As with so many of the paradigm-shifting economic revolutions in the past, once the underlying technologies exist, business and economic models radically adjust to reflect and accommodate that change. The latest of these is the Long Tail economy (r)evolution with it ability to deliver niche (if not personalized) products to niche markets. Pesonalized medicines – regenerative medicine and cell therapies in particular – are the therapeutic industry’s answer for the demand for personalized products. For a host of reasons, however, the economic model is not yet one which makes for profitable delivery of such products to niche markets.

Nonetheless, while questions about the viability of the business and economic models for these paradigm-shifting therapies are reasonable, the next 5 years will show that today’s questions about the business models for cell therapy were rooted in limited imagination about the potential for technological and commercial innovation as well as outdated concepts of the therapeutics industry and its economies.

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[i] Anderson C: The Long Tail: Why the Future of Business is Selling Less of More. Hyperion (2006).

[ii] Friedman TL: The World is Flat. A Brief History of the Twenty-First Century. Farrar, Straus and Giroux (2005).

www.celltherapyblog.com hosted by www.celltherapygroup.com

Let’s get the public services announcement out of the way right up front.

• CellTherapy 2010. Save the date. Submit your session ideas. www.celltherapy2010.com

• While you’re planning your calendar, plan on the 2009 World Stem Cell Summit September 21-23, 2009. Baltimore Convention Center Baltiomore, Maryland. (the 2008 World Stem Cell Summit webcast and downloadable World Stem Cell Report are at www.worldstemcellsummit.com).

• Curiously, the Regenerative Medicine Foundation (I know. I hadn’t heard of it either until now.) has announced that its “Translational Issues in Regenerative Medicine” conference is the “premiere event for leaders in regenerative medicine translation, representing academic research, clinical, healthcare policy, regulatory, reimbursement, investment and biotechnology industry interests.” Curious because it has yet to ever occur. That being said, if they do what they promise, it may just well be. I’m trying to learn more and when I do I’ll let you know. Meantime, this is about all I know:
  

Spring 2010
Twin City Quarter
Winston-Salem, NC

“…to facilitate business development opportunities, the conference will feature a venture forum including 15 regenerative medicine companies, as well as partnering sessions.“

____________________________________________________
Do yourself a favor. Stop monkeying around with home-made cryopreservation brew or, for than matter, any media not built to minimize cellular damage from freezing and thawing.

Do your cells a favor. Try CryoStore and HypoThermosol.

www.biolifesolutions.com

_____________________________________________________

I’m dedicating this issue of Cell Therapy Industry HiLites to TiGenix NV (NYSE EURONEXT: TIG). TiGenix wins the Cell Therapy Group “kick-ass cell therapy company of the week” award which is, of course, something I just made up but they had have a great week raising several million dollars, announcing plans for a new European facility, and receiving a positive opinion from the EMEA CHMP which all but assures them of an MAA within 90 days applicable in 30 European countries. See details below.

FINANCE

TiGenix (NYSE EURONEXT: TIG) has secured the necessary financing to fund the set-up of a GMP manufacturing facility in Europe through a private placement for a total amount of EUR 5,4 million. The investment agreement was subscribed by NV Industriebank LIOF, Particon BV, Limburg Ventures BV and LRM NV. The funds will be used to set up a new cell expansion facility in Europe for the commercial production of its cell based products in the Netherlands. The financing for the facility has been secured through a private placement. After carefully evaluating a number of options throughout Europe, taking into consideration technical, logistical, regulatory and financial criteria, TiGenix has selected a building on the Chemelot Campus, near to Maastricht, the Netherlands, to locate its new cell expansion facility. The site is centrally located in TiGenix’ key European markets, in a region that is strong in distribution and (bio)logistics and that is highly committed to develop as a transnational knowledge centre in life sciences and regenerative medicine.

This financing has now been completed following the execution of a long term lease agreement for the facility in question.

**

After raising $40+ million last year and over $14 million so far this year, Cytori Therapeutics Inc (NASDAQ: CYTX) has announced it has entered into an agreement to raise up to another $20 million over the next year. The company announced recently that it had raised $850,000 in what is described as an agreement by Orlando, FL-based fund, Seaside 88, to buy 7.15 million shares over the next year by buying a specified allotment every two weeks at an agreed discount of the then current stock price. The agreement could being in roughly $20 million for the company depending on share price. Cytori intends to use the proceeds to “accelerate marketing efforts and continue our investment in clinical trials to broaden the number of potential applications for which the Celution® System may be applied”.

**

A bankruptcy court hearing is scheduled for July 6 in which Isolagen Inc. (AMEX:ILE) will request final approval of its debtor-in-possession financing plan under Chapter 11 bankruptcy reorganization protection.

**

Always a master at the art of spinning good profile, NeoStem, Inc. (NYSE: NBS) (AMEX: NBS), in the business of collection, processing and long-term storage of adult stem cells for future medical need, garnered a feature in Gene Marcial’s prominent Business Week column, “Inside Wall Street,” on June 18, 2009. The same week saw the company profiled in a piece on the investment potential for adult stem cell businesses in a Fortune Magazine article distributed by CNNMoney.com. The company has been on a deal-making, press release and publications tear the past few months. “Big plans by tiny NeoStem (NBS),” Mr. Marcial observed, “have helped catapult its stock to $2.27 a share from 50 cents on March 9.” It must be the plans because the company which has been doing what it does since 2006, generated a mere $45,100 in total revenuefor the three months ended March 31, 2009. The good news is that is up from the $700 generated in the three months ended March 31, 2008.

The company also announced another deal saying it has signed an exclusive 10-year agreement with Enhance BioMedical Holdings Limited, a Shanghai corporation, to develop a Stem Cell Collection and Treatment Network using NeoStem’s “technologies” Taiwan, Shanghai and the Chinese provinces of Jiangsu, Zhejiang, Fujian, Anhui and Jiangxi. Enhance BioMedical Holdings is a subsidiary of Enhance Holding Corporation, a multinational conglomerate whose CEO, Jackson Ling, recently invested $5 million in an $11-million private placement financing for NeoStem.

CLINICAL

Osiris Therapeutics, Inc. (NASDAQ:OSIR) announced six-month interim data from a Phase II clinical trial evaluating Prochymal, the Company’s formulation of adult mesenchymal stem cells, for the treatment of chronic obstructive pulmonary disease (COPD). The trial failed to demonstrate an improvement in pulmonary function in COPD patients. The company, quickly becoming practised at spinning what might be considered bad news, said they were pleased the data did provide additional evidence of safety for the product in addition to demonstrating significantly decreased inflammation in the COPD patients. Sixty-two patients were enrolled and are being followed for two years in the placebo-controlled study.

**

Pluristem Therapeutics Inc. (NasdaqCM:PSTI) (DAX: PJT) received approval from the Paul Ehrlich Institute to begin clinical trials evaluating the company’s placental-derived adherent stromal cell product, PLX-PAD, for the treatment of critical limb ischemia.

**

Aastrom Biosciences’ (NASDAQ:ASTM) trial of its cell therapy for severe chronic heart failure was released from a clinical hold by the FDA. The the agency determined the therapy did not cause the death of a participant which resulted in the hold in May.

**

The University of Pittsburgh Cancer Institute began enrolling patients in a Phase III study evaluating the safety and efficacy of Gamida Cell Ltd’s StemEx cord blood stem cell therapy for the treatment of blood cancers.

**

Having received regulatory approval late last year to proceed with its clinical trial in New Zealand, Living Cell Technologies Limited (ASX:LCT; OTCQX:LVCLY) CEO Paul Tan said enrolment of patients should be complete in about two months to begin testing their pig islet cells implanted in humans to treat diabetes.

**

Neuralstem, Inc. (NYSE Amex: CUR) has entered into a sponsored research agreement with the China Medical University & Hospital of Taiwan, in Taichung, Taiwan, to prepare for a human clinical trial using Neuralstem’s human spinal cord neural stem cells to treat stroke patients. The therapy will focus on patients whose post-stroke symptoms, including complete or partial paralysis, have stopped improving more than six months after an ischemic stroke.

COMMERCIAL

Not to be outdone by finance and operational teams, the regulatory team at TiGenix also announced reason to celebrate this week. TiGenix (NYSE EURONEXT: TIG) announced that the company received a positive opinion from the Committee for Advanced Therapies (CAT) and the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA) on the European Marketing Authorisation application (MAA) for
its lead product ChondroCelect.

CHMP opinions are forwarded to the European Commission for adoption of the final community Marketing Authorisation, which is typically issued between 60 and 90 days from adoption of the CHMP opinion. I’m told that European Commission generally follows the advice of the CHMP but, as Dendreon, there’s little reason to celebrate until the formal approval is formalized. For the EMEA take and related info on the decision, click here.

Upon approval, ChondroCelect will be, I believe, the first product approved under the new ATMP regulatory framework. It will certainly be the first cell based product to be centrally approved in the 27 member states of the European Union as well as in Iceland, Lichtenstein and Norway under the new Advanced-Therapy Medicinal Products (ATMP) legislation.

**

Further to my March 31 speculation about who might be the buyer of York Pharma plc (and its two cell therapy products on the market) and my April 13 post that ULURU Inc. (NYSE Amex: ULU) had signed a non-binding offer letter to acquire the company, ULURU Inc. (NYSE Amex: ULU) has announced that at this time discussions to acquire York Pharma, plc have been terminated. ULURU has notified York that the $1 million USD line of credit it had extended York are due plus accrud interest. The revolving credit facility is secured by substantially all of the assets of York and its subsidiaries. York is now actively pursuing alternative funding facilities in order to repay the line of credit within 30 days and to meet its ongoing working capital requirements.

Meanwhile, rumor has it the company is already in talks with another potential suitor.

**

Here are a couple hints for your next press release. It’s rarely newsworthy to have as the primary point of your release an announcement about what you are going to do, rather than what you’ve done; secondly, don’t announce seemingly contradictory information. I’m just saying….

Stem Cell Therapy International, Inc. (OTCBB: SCII), through its wholly owned subsidiary AmStem International, Inc., announced that it has “started the process” to enable it distribute Histostem’s products in anticipation of the finalization of the merger between Stem Cell Therapy International, Inc. and Histostem. This is intented, according to the SCTI President and CEO, to “enable AmStem International, Inc. to begin US distribution and immediately bolster the company’s cash flow”. However, the product has yet to be the subject of a clinical study in the U.S. for which they are seeking “investigators…of the highest caliber, to compare its Stem Cell Facial Cream with others on the market.”

The companies reportedly continue “to work on the necessary steps to finalize the merger, and both sides are working diligently to manage its many details.”

**

Community Blood Services has entered into a licensing agreement with AuxoCell Laboratories, Inc. to use AuxoCell’s exclusive patent rights and propriety process to extract fetal mesenchymal stem cells from the Wharton’s Jelly of donated umbilical cords, allowing Community Blood Services to operate the first Wharton’s Jelly derived stem cell bank in the United States.

**

After netting $221 million last month by nearly 12 million shares at $19.20 apiece, Dendreon Therapeutics Inc (NASDAQ:DNDN) expects to spend up to $50 million in a two-phase expansion of its manufacturing facility in Morris Plains, New Jersey. Monday in a regulatory filing. Additional quality control laboratories, data center, training areas, infrastructure and offices are scheduled to by done by mid-December. The final phase, with additional manufacturing clean-room work stations, production support areas, warehouse, infrastructure and offices, is to be substantially complete by April 23 of next year. Dendreon finished the initial build-out of its 158,000-square-foot facility in July 2006, before its FDA application was tabled to await additional clinical results.

**

Apparently yet another way has been invented to derive stem cells from placenta – reportedly a source much richer in stem cells than umbilical cord blood. The inventors are looking for commercial partners.

**

Cell Genesys, Inc. (NASDAQ:CEGE) – the company that just won’t go away – is still pursuing “strategic alternatives”. Meanwhile, it expects its cash balance will be approximately $36 million upon imminent completetion of its stock exchange offer.

MISCELLANIA

This week’s issue of Science has a special focus on stem cells including a piece on “FDA Regulation of Stem Cell–Based Products” by Donald W. Fink, Jr. of FDA, CBER, an article on stem cell tourism and 3 reviews. 26 June 2009. Vol 324, Issue 5935, Pages 1603-1754

**

The Production Assistance for Cellular Therapies Group (PACT) Educational Web Seminar: Topic: “Deviation Management of Type 351 & 361 Cell Products” Date: Thursday, July 16, 2009 Time: 12:00pm-1:00pm (Eastern US Time) Register is now open for this Web Seminar at www.pactgroup.net.

Sign-off

Thanks again to BioLife Solutons. Congratulations to Tigenix. May the force be with all of you and for those going to ISSCR later this week….safe travels and please try not to enjoy Barcelona too much without me!

www.celltherapyblog.com hosted by www.celltherapygroup.com

This week I’m ROTFLMAO loving this cartoon so I thought I’d share the chuckles (thanks to www.onstartups.com). I can’t tell you how many times in the past years I’ve seen the inevitable ‘hockey stick’ market projections graph from companies, analysts, and investors when discussing the coming 5 years in the cell therapy sector. It’s become a standing joke about how we just keep pushing the hockey stick out to the right but the curve is inevitably the same. This pokes a little fun at this much maligned tradition.

Maybe it’s just because I’m Canadian that I love this so much but c’mon the beloved hockey stick has become almost more a marketing tool than the venerable piece of sports equipment every Canadian boy must own! Maybe we can adapt this new hockey stick model to give the over-used Gartner cycle a run for its money!

Down to business…

I was told last week that Senators have been inviting people to Capital Hill to speak to them about FDA regulation of adult stem cells perhaps at the instigation of Chris Centeno’s lobbying through ASCTA (www.stemcelldocs.com) that the medical use of moderately expanded autologous adult stem cells should not be regulated by the FDA but rather self-regulated by physicians. This could, of course, have serious implications on business models for autologous cell therapy companies. I’ve heard nothing of the Senators asking for ISSCR or ISCT counsel to-date. It would, of course, likely be Centeno’s position that anyone involved in those orgs are “pharma hacks” as he has accused me of being.

ASCTA which is comprised of physicians none of whom are acknowledged leaders in stem cell research recently proudly announced the release of their stem cell guidelines which they suggest should replace FDA regulation. In what appears to be simple ignorance of the years of work being done by AABB & FACT, ASCTA described their guidelines as “the world’s first clinical guidelines to allow U.S. doctors to safely begin using the patient’s own stem cells to treat disease.” Their lab practice guidelines contain such gems as:

• Any facility used in the processing A-ASC’s must be of suitable size, construction, and location to prevent contamination.
• The facility should be in a good state of repair.
  
• Equipment used in the facility should be adequately maintained
• In humid areas, dehumidifiers should be used to control the spread of infectious agents in the lab.
• Any reagents used must be approved for human use (where practical).

In an online posting entitled “The FDA is Killing Adult Stem Cell Therapy Thus Killing Patients“, ASCTA supporter, Don Margolis, states:

In a startling new interview on stem cell research and adult stem cells in the near future, Dr. Christopher Centeno warns that Big Pharma and the FDA are teaming to control the use of a person’s own stem cells thus slowing innovation and the use of Adult Stem Cells to help patients now.

FINANCIAL

ReNeuron Group plc (LSE: RENE.L) has raised the £3 million it announced it intended to raise. ReNeuron recently received regulatory approval to commence a Phase I clinical trial in the UK with its lead ReN001 stem cell therapy for disabled stroke patients. The Company is developing stem cell therapies for a number of other conditions, including peripheral arterial disease and diseases of the retina. ReNeuron has also developed a range of stem cell lines for non-therapeutic applications – its ReNcell® products for use in academic and commercial research. The Company’s ReNcell®CX and ReNcell®VM neural cell lines are marketed worldwide under license by USA-based Millipore Corporation.

Pfizer expects to pump $100 million into its international stem cell development program which aims to focus both on small molecules that work by modifying cells in the body and cell therapy where the cells are manipulated outside the body. The first major use of the Pfizer money is for a collaboration with University College London (UCL) for the treatment of certain forms of blindness through the London Project to Cure Blindness. The collaboration will attempt to develop stem cell-based therapies primarily for wet and dry macular degeneration (AMD), which Pfizer has the rights to progress through clinical trials and then commercialize. Pfizer’s work on this could potentially provide a boost for the cash-strapped and searching-for-a-buyer, Intercytex Group plc (AIM: ICX), whose involvement on the London Project could yield cash royalties. But that’s not where the Pfizer-Intercytex connection may end, apparently. Reports indicate that Pfizer is in fact eyeing the troubled Intercytex as a potential acquisition or investment. The company is on the auction block and actively seeking suitors.

Cytori Therapeutics, Inc. (NASDAQ: CYTX) expected to close a private placement for $4.2 million by May 11. No word yet…

Aastrom Biosciences, Inc. (Nasdaq:ASTM) temporarily suspended enrollment and patient treatment in its U.S. Phase II IMPACT-DCM clinical trial following a report that a patient died at home after being released from the hospital following treatment in the trial. IMPACT-DCM is a clinical trial to evaluate the surgical delivery of autologous cells directly into the human heart muscle for the treatment of congestive heart failure associated with dilated cardiomyopathy (DCM) in both ischemic and non-ischemic patients. The patient’s cause of death has not yet been determined and is the subject of a pending investigation at the clinical site. An independent Data Safety Monitoring Board (DSMB) will also assess the circumstances of the event. The Company has voluntarily suspended patient enrollment and treatment in the trial and the FDA placed the trial on temporary clinical hold pending an investigation.

ImmunoCellular Therapeutics, Ltd. (OTC: IMUC.OB ) (IMUC) announced that clinical data from the company’s Phase 1 trial of its antigen-pulsed dendritic cell immunotherapeutic cancer vaccine ICT-107 for patients with brain stem glioma and glioblastoma will be presented at this year’s ASCO. Having said that, they also said that while “encouraging data” was observed from the phase I trial of ICT-107, IMUC’s primary focus going forward will be on its lead product candidate, ICT-121, which is an peptide-based “off-the-shelf” cancer vaccine that targets cancer stem cells and may have applicability to multiple types of cancer. IMUC anticipates filing an Investigational New Drug (IND) application in the third quarter of 2009 for a Phase I trial of ICT 121 in the treatment of glioblastoma (brain cancer).

COMMERCIAL

Cytori Therapeutics (NASDAQ:CYTX) and GE Healthcare, a unit of General Electric Company (NYSE:GE) announced an agreement by which GE Healthcare will commercialize Cytori’s StemSource(R) technology in the North American stem cell banking and research markets. The StemSource technology includes automated equipment to process stem and regenerative cells found in adipose tissue, cryopreserve them or use them directly for research purposes. In January 2009, Cytori and GE Healthcare formed a separate agreement to commercialize Cytori’s products in ten European countries. This includes selling the Celution(R) 800/CRS System in the European cosmetic and reconstructive surgery market as well as selling StemSource products in the European cell banking and research markets. The recent partnership is similar in nature to the European agreement, but is limited to the sale of StemSource banking and research products in the U.S., Canada and Mexico for 18 months starting in the second quarter of 2009. The agreement does not include U.S. commercialization of Cytori’s Celution System, which is currently under review by the FDA.

After securing a $12M equity financing facility and closing a $1.5M private placement, formerly on-the-rocks Melbourne-based Prima BioMed (ASX: PRR), which had less than $500,000 in the bank at the end of December, is now preparing IND filing in the US for a phase IIb / III pivotal trial of CVac for ovarian cancer. As previously reported here, the company has also commenced CVac™ ovarian cancer treatments on selected patients in Australia made possible through the Australian Government’s Australian Regulatory Control Mechanism’s Special Access Scheme under the Therapeutic Goods Administration. Meanwhile the company is looking at taking the product to other countries as a means of generating cash flows in the short-term through the sale of CVac™ treatments. Now the company’s executive director, Mr Martin Rogers, is touring North America in discussions with a number of hedge funds and other biotech focused investment funds about new investment and partnering opportunities for the commercialization of CVac.

Progenitor Cell Therapy, LLC has done a deal with NeoStem, Inc. (NYSE Amex: NBS) as their exclusive provider of commercial adult stem cells processing and storage. Progenitor founder, Andrew L. Pecora, has also joined NeoStem’s Advisory Board.

NeoStem, meanwhile, – the new favorite company of alternative “medical” products promoter, Suzanne Sommers – has been busy the last few weeks creating a curious empire of sundry types of bedfellows. Recently the company announced it had signed an agreement to license the exclusive worldwide rights to a technology, with pending patent applications, developed by Vincent Falanga, M.D., Chairman of the Department of Dermatology and Skin Surgery at Roger Williams Medical Center, Providence, R.I. Dr. Falanga’s stem cell product under development, Primcel, is a mesenchymal stem cell (MSC) product. Early clinical studies are said to indicate that Primcel can be used to accelerate or jump start healing of chronic wounds. Dr. Falanga’s work seeks to develop a prepackaged product created from a patient’s own cells, ready for physician use in a clinical setting, consisting of three applications over a 12-week period.

Almost in the same breath, the company filed a patent application claiming the proprietary stem cell technology of Vincent C. Giampapa, M.D., F.A.C.S. relating to cosmetic facial rejuvenation, which NeoStem first licensed in February 2009. Dr. Giampapa is director of the Giampapa Institute for Anti-Aging Medical Therapy, a board-certified plastic reconstructive surgeon and Assistant Clinical Professor of Plastic and Reconstructive Surgery at the University of Medicine and Dentistry of New Jersey. His cosmetic stem cell face lift technology is said to comprise a “non-surgical procedure for complete facial rejuvenation that involves injecting pluripotent cells, including stem cells, into the skin of individuals whose skin has lost its firmness and texture due to age“.

Days later NeoStem announced it had signed an exclusive royalty-bearing license agreement for the Asia territory for a procedure developed by Regenerative Sciences, LLC and marketed for the treatment of chronic orthopedic conditions, under the name, Regenexx. Additionally, Regenerative Sciences, through its founder and CEO, Christopher Centeno, M.D., will serve as a consultant to NeoStem, Inc. in the area of stem cell therapy in orthopedics.

Undoubtedly Centeno will also embroil and leverage NeoStem in his fight with the FDA about the marketing of Regenexx in direct flagrance of FDA regulation. In any event this is clearly a solid “plan B” for Centeno should the FDA ever get around to shutting him down in the U.S. In the interim, Centeno continues to strengthen his network of supporters and is reportedly actively working Capital Hill for support for his fight.

To mix it up a little, NeoStem then announced they had signed a deal to promote and glean royalties from the sale of a liquid, nutritional supplement – AIO Premium Cellular Health. Not kidding. They have signed an agreement for Ceres Living, Inc., a developer and direct marketer of health and wellness products. AIO Premium Cellular Health was apparently developed in conjunction with NeoStem’s scientists and Advisory Board members, based on certain nutraceuticals that have been shown to “optimize stem cell functions”. The promotion of AIO is said to be “part of NeoStem’s corporate commitment to advancing anti-aging and regenerative medicine therapies and technologies.”

Novocell, Inc. announced that it has received U.S. Patent # 7,534,608 with with wide-ranging method claims covering the Company’s innovative stem cell therapy for the production of functional pancreatic, insulin-producing cells from human embryonic stem cells (hES). Novocell’s therapy is being developed as a method for the use of hES cells to replace insulin-producing pancreatic cells that are destroyed in people with diabetes.

Neuralstem, Inc. (NYSEAmex:CUR) recently published a reaction to a press release by StemCells, Inc. (STEM) refuting many of their statements in what has become a very public dispute. Included in the reaction is the claim that “the PTO upheld the patentability of Neuralstem’s core technology in May, 2006, in response to a challenge from STEM” and that the Neuralstem “patents are not being challenged in the PTO or in any of the suits with STEM”.

This is not a cell therapy story but it could be. Takeda Pharmaceutical Company Limited (TSE: 4502) and IDM Pharma, Inc. (Nasdaq: IDMI) today announced that Takeda America Holdings, Inc., a wholly-owned subsidiary of Takeda (Takeda America), and IDM Pharma have entered into an agreement for Takeda America to acquire IDM Pharma. Takeda America has established Jade Subsidiary Corporation as a wholly-owned subsidiary to effect that transaction. Under the agreement, Takeda America will purchase all of IDM Pharma’s outstanding shares for US$2.64 per share in an all cash tender offer followed by a merger.

You may recall that on April 1 last year (omen perhaps?), Cell Genesys, Inc. (“Cell Genesys”, Nasdaq: CEGE) and Takeda announced that the companies had formed a global alliance for the development and commercialization of GVAX immunotherapy for prostate cancer, Cell Genesys’ lead product candidate then in Phase 3 clinical development. Under the agreement, in exchange for exclusive worldwide commercial rights to GVAX immunotherapy for prostate cancer, Takeda was to pay Cell Genesys an upfront payment of $50 million and additional milestone payments totaling up to $270 million relating to regulatory approval and commercialization of GVAX immunotherapy for prostate cancer in the United States, European Union and Japan.

This deal quickly unraveled when they decided to mothball both phase 3 studies of GVAX on statistical likelihood of failure. This was Takeda’s big venture into cell therapy and it is an ugly, recent memory. Now they have bought IDM Pharma. They ‘ve bought it for the company’s primary asset, MEPACT, (mifamurtide), a macrophage activator drug therapy indicated for the treatment of non-metastatic osteosarcoma (malignant bone cancer) following surgical removal of the tumor (resection) in children, adolescents and young adults.

Here’s the cell therapy part: IDM Pharma has 3 autologous cell therapy products currently on developmental hold as a means of perserving resources to get them to the home run on MEPACT. BEXIDEM is activated macrophages (Monocyte-derived Activated Killer cells or MAK® cells) for bladder cancer. UVIDEM, for melanoma, and COLLIDEM, for colorectal cancer, are both therapies using dendritophages (specialized immune cells derived from the patient’s own white blood cells). It will be very interesting to see what Takeda does with these products, if anything.

Veterinary stem cell company, Vet-Stem, Inc, has now expanded from its US base into Canada, providing commercially available autologous, adipose-derived stem cell tranplants for horses and dogs.

MISCELLANEA

International Stem Cell Corporation (OTCBB:ISCO), the company behind human stem cells from unfertilized eggs (called “parthenogenetic stem cells”), submitted comments to NIH on their draft stem cell research guidelines issued by the National Institutes of Health (NIH) on April 17, 2009. ISCO then published its comments in a press release and then their CEO published a blog to address questions regarding their comments.

Genetics Policy Institute also submitted a letter to the National Institutes of Health (NIH) commenting on the Draft Guidelines for Human Stem Cell Research. The complete letter is available at www.genpol.org for public viewing.

The California Institute for Regenerative Medicine is working its way through Congress seeking $500 million in federal funds it hopes to apply toward guaranteeing the long-planned small-business loan program.

Forbes published what is actually quite an informative article on cell therapy medical tourism for a change.

Sign-off

If you’ve read this far you’re obviously interested in the cell therapy industry. If you’re on LinkedIn make sure you have joined the LinkedIn Cell Therapy Industry Group.

Thank you all for all your good wishes about the new addition to my family – my own little sample of regenerative medicine! Now I gotta go and spend some time with her before I’m enrolling her in college…

Remember. Cell Therapy Means Business.

www.celltherapyblog.com hosted by www.celltherapygroup.com

“Autologous manufacturing is not the deal breaker it used to be. If these [cell-based] vaccines work for really difficult-to-treat diseases, the manufacturing issues will be worked out.” Howard Liang, MBA, Ph.D., Analyst and Biotechnology Managing Direct at Leerink Swan. “Special Report: Customized Cancer Vaccines Finally (Maybe) Arrive“. GEN News Highlights. 12 June 2009.

Amen. Glad to hear someone else saying it.

_______________________________________________________________

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This issue of Cell Therapy Industry HiLites is brought to you by the charming, witty and occasionally useful folks at the cell therapy group.

Looking to access intel from one of the most comprehensive databases in the cell therapy and regenerative medicine industry?

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FINANCIAL

Neuralstem, Inc (NYSE AMEX: CUR) received notice from the NYSE Amex Exchange that its shareholder’s equity has dropped below the $2,000,000 threshold required by the NYSE Amex for continued listing. The Company intends to submit a plan to the Exchange. CEO and President Richard Garr said, “We are confident that the company will be in compliance.”

National Institutes of Health has awarded a $5 million grant to Q Therapeutics (co-founded by former NIH researcher Mahendra Rao), the University of Utah’s Cell Therapy Facility and Johns Hopkins University School of Medicine to start human clinical trials of Q-Cells for myotrophic lateral sclerosis, or ALS — better known as Lou Gehrig’s disease.

Opexa Therapeutics, Inc. (NASDAQ: OPXA) received a favorable ruling from NASDAQ allowing an extension to regain compliance and continue the listing of the Company’s securities on The NASDAQ Capital Market.

CLINICAL

StemCells, Inc. (NASDAQ: STEM) announced positive data from its Phase I clinical trial of its proprietary HuCNS-SC® product candidate (fetal-derived purified human neural stem cells). The six-patient Phase I trial was designed primarily to assess the safety associated with transplanting HuCNS-SC cells as a treatment for infantile and late infantile NCL, often referred to as Batten disease

Celsense, Inc. is one of the recipients in a 4-year $1.95M grant from the National Institutes of Health to test its in vivo cell trafficking MRI reagent in human clinical studies. The funded studies will be the first effort to evaluate Cell Sense, the Company’s fluorocarbon-based magnetic resonance imaging (MRI) cell tracking reagent, for clinical use. Additionally, the studies will garner preliminary data critically important for improving immunotherapeutic delivery strategies in metastatic colorectal (CRC) and other forms of cancer.

The Cell Sense technology makes transplanted cells visible by MRI. Therapeutic cells are labeled ex vivo with the Cell Sense reagent prior to administration to the patient. Cell migration and biodistribution are subsequently monitored using fluorine-19 (19F) MRI or magnetic resonance spectroscopy (MRS).

The key advantage of Cell Sense is purported to be that the 19F images are extremely selective for the labeled cells, with no background signal from the host’s tissues. Furthermore, accurate cell quantification in regions of interest is possible. Existing data from pre-clinical studies using human cells is said to show that the Cell Sense reagent is highly biocompatible inside cells and does not affect their innate function.

A clinical-grade version of the Cell Sense reagent has been formulated by Celsense, Inc. and is currently being subjected to mandatory in vitro and animal safety studies in preparation for human trials.

Never a company to shy away from making bold and early claims, Advanced Cell Technology, Inc. (OTC:ACTC.PK) Chairman and CEO William M. Caldwell IV said earlier this week that they are completing the “finishing touches” on a submission to seek FDA approval to conduct human clinical trials with a cell therapy that may be able to address many of the 200 plus known retinal diseases.

COMMERCIAL

It’s hard to put this story under any one category but since the financial terms weren’t released and it’s not yet clinical, I’ll call it “commercial”. J&J’s Ortho Biotech Oncology Research & Development, a unit of Centocor Research & Development, Inc., has announced that it has entered into a five-year Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI), with Steven A. Rosenberg, M.D., Ph.D., chief, Surgery Branch, serving as the NCI principal investigator, to research and develop novel cell therapy technologies as potential treatments for a variety of cancers.

The deal bring together Ortho’s and Rosenberg’s adoptive immunotherapy technologies designed to work by helping the immune system fight cancer.

Rosenberg has been a pioneer in the field of adoptive immunotherapy of cancer developing Tumor Infiltrating Lymphocytes (TILs) – T cells obtained from a patient’s tumor, expanded and then re-administered to actively seek and destroy cancer cells. In recent years, Dr. Rosenberg’s team developed a new technology in which T cells obtained from a patient’s blood are genetically engineered to express receptors that give them specific immunity against cancer cells and then re-administered.

Meanwhile, researchers at Ortho Biotech Oncology Research & Development independently developed a different and proprietary adoptive immunotherapeutic approach that uses tumor antigens and other materials to stimulate T cells from a patient’s blood to become Cytotoxic T Lymphocytes (CTLs), which recognize and attack tumor cells.

Both technologies show postive early clinical results in melanoma, a type of skin cancer that ranks sixth among U.S. men and seventh in U.S. women for the most commonly diagnosed cancer, according to the NCI.

Under the CRADA, Dr. Rosenberg’s lab will conduct a clinical trial in melanoma patients using Ortho Biotech Oncology Research & Development’s proprietary technology. It is hoped that the technology will be effective in other types of cancer, as well.

They expect to begin clinical testing of the immunotherapy technology in melanoma patients by the end of 2009, with the possibility of additional studies for other types of cancer and other technologies in years to come.

Cellular Dynamics International, Inc. has secured an exclusive license on a patent portfolio surrounding cardiovascular progenitor cells. The license covers differentiation of stem cells into all cell types of the human heart. The patent portfolio was generated by and obtained from Gordon Keller, Ph.D. and Mount Sinai School of Medicine.

Cardiovascular progenitor cells are capable of further differentiation into the multiple cell types of the heart, including cardiomyocytes, endothelial cells, and vascular smooth muscle cells, both in vitro and in vivo. CDI intends to commercialize the technology to the pharma and biotech industry for predictive toxicology and screening purposes. Iit’s not clear whether the license also includes clinical applications but if so they may be looking for licensing partners given their current lack of interest in developing these cells into therapeutics.

In a not-so-surprising move, StemCells Inc (NASDAQ: STEM) has decided to close StemCell Sciences in Melbourne, Australia after its acquisition of the company in March. British staff will now be holding their breath to see if the same will happen to them. STEM says it has offered relocation packages to employees should they wish to move to sunny California. This leaves one “stem cell” firm in Australia where previously there were four (SCS, Bresagen, Embryonic Stemcells Inc and Mesoblast). If there is good news it is that, if I recall correctly, the three others were acquired and not just shuttered.

After many months of actively looking to offload its contract manufacturing subsidiary, Fresenius Biotech, has finally sold EUFETS AG to BioNTech AG. BioNTech is looking ot leverage the acquisition to further its quest to develop innovative molecular immunotherapies and biomarker based diagnostic approaches for individualized treatment of cancer and other severe human diseases.

StemCyte Therapeutics is collaborating with Chennai-based Apollo Hospitals in joint venture with Ahmedabad-based Cadila Pharmaceuticals to set up what reports to be a first-of-its-kind umbilical cord blood (UCB) public bank for India.

“No more pads or tampons, period.” Lifecell International is set to introduce in India next month menstrual cups as a cost-effective option to control menstrual flow in women and as a preparatory move for the company’s menstrual-blood banking project called Femme, which is scheduled to begin in July

MISCELLANIA

Xconomy’s Luke Timmerman does a nicewriting up an informative piece on Denderon’s recent AGM and the thinking around the company of what will be involved in taking the company “all the way”.

Ok its another pre-clinical item (which I rarely cover) but again this one’s just too cool to ignore. The New Scientists did a nice job of looking at Doris Taylor’s work at University of Minnesota. Her team is looking to expand on their success creating rat hearts using stem cells. The ultimate goal is to some day create a limitless supply of transplant organs for humans. The team took stripped-down scaffolding of one rat heart and coated it with tissue produced from another rat’s stem cells. They now want to repeat the procedure using hearts and other organs from human cadavers or larger animals.

The NIH received 49,015 comments in response to its draft guidelines for human stem cell research. One of those was submitted by CIRM.

President Barack Obama should appoint a commission on stem cell research to help the therapy fulfill its promise to save lives and reduce medical costs, says Geron Corp. Chief Executive Officer Tom Okarma.

The California Institute for Regenerative Medicine (CIRM) received 73 preapplications for the CIRM Disease Team Awards RFA 09-01. The principal investigator for 15 of those applications is based with a for-profit entity. All of the teams proposed a wide variety of collaborators with several of the not-for-profit principal investigators citing collaborators in the for-profit sector. After review by a panel of outside experts and the CIRM in-house science team, a subset of these teams have been asked to prepare a full application, which will be due to CIRM July 16. Word on the street is that to-date just over 20 of the 73 have been given the green light to the next step.

Sign-off

Organogenesis, Inc has established an annual scholarship program with Canton High School to honor a graduating senior pursuing a career in life sciences research or biomedical engineering. Kudos for them. We need more of that! Me? I sponsored a child this week. No big deal but it reminds me to remind you…

…find a way to make a difference in your world today.

One more thing. You want to make sure you hear cell therapy-related news faster? Get on Twitter and follow me. I’m @celltherapy.

Ok. Hope you found that useful. I’m trying to get back to my every Friday schedule here. I’ll do my best. Happy weekend.

Lee Buckler, BEd, LLB
Cell Therapy Group
Principal

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www.celltherapyblog.com hosted by www.celltherapygroup.com

I’m back.

That on the left my friends is the new squawking reason I’ve been quite on the blogosphere and Twitter scene for the past few weeks!

I know this issue of my Industry HiLites has some rather stale news but it also has some recent news. What I can’t promise is that I’ve captured all the cell therapy related news from the past few weeks. I’ll attempt to back fill as time permits.

“Cell Therapy is expected to be one of the most important innovation drivers of modern medicine”. See below who is the source of such zeal!

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If you missed the Invitrogen-sponsored breakfast session at the 2009 Phacilitate Cell & Gene Therapy Forum in Washington, DC, the session videos are now posted for your convenience.

Realizing the potential of cell therapy: new enabling platforms
Brian Newsom, Cell Therapy Business Development Leader, Invitrogen/Life Technologies

Exciting lentiviral platform technology applicable to clinical indications from leukemia to HIV
Dr. Boro Dropulic, President and Chief Scientific Officer, Lentigen, Inc.

20-year history of Organogenesis
Katie Faria, Director, Process Development, Organogenesis, Inc.

Contact them at celltherapysystems@invitrogen.com if you want to engage in a discussion about how Invitrogen™ Cell Therapy Systems can deliver proven products and expertise to help with your translational research and clinical development plans. Find more videos and information about their products and services (including immunotherapy, stem cells, and tissue engineering) go to www.invitrogen.com/celltherapy.
______________________________________________________

The race is on between Dendreon and Osiris to be the first cell-based therapeutic approved in over 10 years. Osiris Therapeutics, Inc. (NASDAQ:OSIR) has confirmed with the U.S. Food and Drug Administration, receipt of the first portions of its BLA (Biological License Application) for Prochymal as part of a rolling submission. Dendreon expects to file revisions to its already-filed BLA by Q4 of this year. If things go as Mitch Gold (Dendreon CEO) predicts, it looks like Dendreon will win the race to market but they are not competitive products and everyone wins if they are both approved regardless of the order!

Meanwhile, troubled cell therapy company Isolagen, Inc. (AMEX: ILE) received good news from FDA recently that its BLA has been accepted for full review – decision due by Jan 4.

FINANCIAL

Cell therapy company Isolagen, Inc. (AMEX: ILE) received bridge financing to allow it to seek debtor-in-possession financing in conjunction with a possible chapter 11 filing. Meanwhile, they’ve filed their latest 10Q with the SEC for those interested in the gory details.

The California Institute for Regenerative Medicine (CIRM) has handed out 15 grants worth $67.7 million to 13 not-for-profit and two for-profit organizations, BioTime and Novocell. An additional 12 grants which were recommended are on hold and money will made available only if funds allow. They will consider those grants in June. Novocell has been awarded $5,405,397 for its embryonic stem cell-derived diabetes therapeutic program and BioTime has been granted $4,721,706 to facilitate the use of its ACTCellerate™ technology for manufacturing patient-specific therapeutic products through the expansion of over 140 highly purified primitive human embryonic progenitor cells (hEPCs) from hES or iPS cells.

Novocell will receive two funding awards totaling $6.2 million from CIRM. The grants cover development of methods for delivery and monitoring safety of human embryonic stem cell (hESC)-derived pancreatic cells for diabetes cell therapy.

Virxsys Corp. of Germantown, Md., and Rockville’s GlobalStem Inc. are the only two private companies among the recipients of nearly $19 million of funding for stem cell projects granted recently by the Maryland Stem Cell Research Commission to 59 projects out of 147 applications that it received. GlobalStem’s project is entitled “Scale-Up Manufacturing, Authentication, and Banking of Human Pluripotent Stem Cells” and curiously Virxsys’ is “Developing safer methods for induced Pluripotent Stem (iPS) cell generation using Spliceosome-mediated RNA trans-splicing (SMaRTTM) technology”.

While functionally the company is in a deep coma for the moment, according to a recent SEC filing, Cell Genesys, Inc. (NASDAQ:CEGE) is continuing to explore financing alternatives and consider strategic alternatives, including merger with or acquisition by another company, further restructuring, other sales of non-core assets, and other potential technology outlicensing or liquidation of the company.

Embryome Sciences, Inc. parent co BioTime, Inc. (OTCBB:BTIM) has raised $4M with a possible $16M in total with the potential sale of additional shares and warrants.

CLINICAL

Pervasis Therapeutics received Orphan Drug Designation for Vascugel cell therapy as they
prepare for a phase III trial of the product.

Osiris Therapeutics, Inc. (NASDAQ:OSIR) completed patient enrollment in the second of its Prochymal Phase III trials for Graft vs. Host Disease (GvHD).

I have to confess that until I read this recent press release from ReNeuron I was suffering under the misconception that the regulatory framework for cell therapies in Europe was becoming clearer but listen to this nightmarish-sounding bureaucratic cluster-schmuck. ReNeuron Group plc (LSE: RENE.L) provided a regulatory update regarding its ReN001 stem cell therapy for stroke. In January of this year, the UK Medicines and Healthcare Products Regulatory Agency (MHRA) granted regulatory approval for a Phase I clinical trial with ReN001 in disabled stroke patients, to be undertaken in Scotland at Glasgow Southern General Hospital. The decision was ratified by the Commission on Human Medicines, with the support of its Clinical Trials Expert Advisory Group which was also involved in reviewing the application.The Company has since submitted the clinical trial application to the Gene Therapy Advisory Committee (GTAC) who, in addition to their existing gene therapy remit, were recently given responsibility to act as the national research ethics committee for stem cell therapy clinical trials in the UK. The Company has been notified by GTAC that a Provisional Opinion has been granted in respect of the applicatio , subject to the resolution of a small number of points raised pertaining to non-safety-related pre-clinical data and the clinical trial protocol. The Company is reportedly currently working to respond to the points raised, the majority of which involve straightforward amendments to the clinical trial protocol. Further clarification is being sought by the Company, particularly within the context of the above-mentioned regulatory approvals already received, regarding one request for further non-safety-related data by GTAC, the provision of which would potentially delay the start of the clinical trial by a few months. Meanwhile their IND in the U.S. remains on hold after well more than a year has passed since its submission.

Cellerant Therapeutics, Inc. announced the dosing of the first patient in a phase 1 trial of CLT-008 for hematological malignancies. CLT-008 is an allogeneic cell therapy designed to rapidly produce mature neutrophils and platelets in vivo and facilitate long-term engraftment in patients undergoing bone marrow or cord blood transplantation, or being treated for chemotherapy- or radiation-induced neutropenia among other applications. CLT-008 is said to have the potential to make cord blood transplants safer and more available for everyone regardless of age, size, or ethnic and racial background. In preclinical testing CLT-008 has reportedly shown to provide hematopoetic support to enable long-term engraftment of blood-forming stem cells, which could lead to broader use of cord blood transplants as an effective therapy for multiple life-threatening blood diseases. The company intends to study CLT-008 to addresses several significant markets and including neutropenia in the near future.

Led by Dr. John Wagner, Professor of Pediatrics and Director of the Division of Hematology-Oncology and Blood and Marrow Transplantation at the University of Minnesota, the Phase 1 study is an open-label, dose-escalation trial and will investigate the safety and tolerability of CLT-008 in 20 to 25 patients undergoing cord blood transplants.

Ever-innovative Medistem Inc. (PINKSHEETS: MEDS) is bringing pre-clinical research, commercial cell therapy clinical practice outside the U.S., and veterinary stem cell protocols together to report positive multiple sclerosis data using fat stem cells. A recent paper describes the scientific rationale and preliminary results of three patients with multiple sclerosis treated with their own fat derived stem cells. The paper provides some evidence that a stem cell-rich component of adipose tissue, called the Stromal Vascular Fraction, can concurrently immune modulate, while inducing regenerative activities in multiple sclerosis patients.

Publication collaborator, Dr. Robert Harman, CEO of Vet-Stem, has treated over 3,500 horses and 1,500 dogs with fat derived stem cells for inflammatory conditions such as osteoarthritis immune-mediated polyarthritis. The article, titled “Non-expanded adipose stromal vascular fraction cell therapy for multiple sclerosis,” appeared today in the Journal of Translational Medicine (http://www.translational-medicine.com), and was a collaboration between scientists and clinicians from Medistem; the University of Western Ontario; Hospital CIMA, San Jose, Costa Rica; Indiana University; Cell Medicine Institutes; University of California, San Diego; and University of Utah

COMMERCIAL

Finally, we hearing some more about David Mooney’s company InCytu, Inc. which makes “smart biopolymer devices that enable in vivo cell programming”. I hear a lot of great talks but I have to confess hearing Mooney speak last year topped the list for 2008. This stuff might be too intelligent (read “complicated”) to be commercializable but it certainly doesn’t lack for brilliance.

The first of their in situ bioreactive devices (iBDs), coined Cellarium(TM) by the company, will be an intelligent biopolymer scaffold that once implated releases a factor that selectively attracts dendritic cells (DCs) into the scaffold, presents antigenic (melanoma specific) proteins to them, and then, upon maturation, releases the activated DCs to home to the lymph nodes where they stimulate T cells to specifically attack the melanoma.

This takes the whole notion of cell therapy (traditionally involving the ex vivo manipulation of harvested cells for implantation) and turns it on its head by doing in vivo what we have believed can/must be done in cGMP facilities.

Now this is all a long way off and the Lord Almighty knows we have had more than our share of cell-based cancer vaccine failures but other applications in the pipeline include chronic ischemia, peripheral vascularization, muscle regeneration and even potentially stroke and CNS disease.

InCytu plans to develop partnerships for product sales and marketing but retain control of the cGMP production of its iBD devices. The company’s product development facility is in Lincoln, RI likely for reasons associated with its CEO – serial CEO and cell therapy entrepenuer, Alfred Vasconcellos, who has been involved with CytoTherapeutics, ETEX, LCT, Sertoli Technologies. LCT Biopharma, Multicell, and cut his early teeth in Pfizer’s Strategic Market Development group. Vasconcellos was most recently the CEO of LCT Biopharma Inc. which is the wholly owned subsidiary of diabetes cell therapy company Living Cell Technologies Ltd (listed on the Australian Securities Exchange (ASX:LCT) and the US-based OTCQX (OTCQX:LVCLY) from New Zealand and now conducting a trial in Russia.

Dendreon (NASDAQ:DNDN) CEO Mitchell Gold’s ship came in when he recently sold 600,000 shares of the company at $24.92 apiece on April 29, generating gross proceeds of $15 million.

Meanwhile Dendreon is going on a hiring binge in prep for FDA approval of Provenge.

It is interesting to see the different approaches companies take to competitive IP. Whereas Osiris appears content for the moment to let companies develop all kinds of MSC products without interference, Stem Cells, Inc couldn’t be more aggressive in litigating any IP they believe infringes on their patents, like that of Neuralstem. Cytori and Vesta had a similar battle.

StemCells, Inc. (NASDAQ:STEM) recently announced that the U.S. Patent and Trademark Office (PTO) has upheld the validity of the remaining two neural stem cell patents which were subjected to reexamination proceedings commenced by Neuralstem, Inc. The upheld patents are the subject of two related lawsuits initiated by StemCells against Neuralstem, which allege infringement of a total of six patents. These six patents collectively claim the manufacture and use of human neural stem and progenitor cells as tools for drug discovery and as therapeutic agents. The PTO’s decision to uphold the two patents is final and cannot be appealed. Consequently, StemCells is asking the federal district court in Maryland to resume the infringement lawsuits against Neuralstem.

“The PTO’s latest action is a reaffirmation of the validity of the patents asserted against Neuralstem. Each of our reexamined patents has now been twice tested and twice granted by the Patent Office,” said Martin McGlynn, President and CEO of StemCells, Inc. “We now look forward to our day in court. Litigation can be a slow and meticulous process, but we plan to ensure that those who wish to commercialize neural stem cells for drug discovery or therapeutic uses, recognize the validity and value of our patents.”

Pfizer is clearly seeing ocular therapies as an important franchise for its regenerative medicine enterprise. After making a seed-like investment of $3M last year in the startup EyeCyte Inc, Pfizer has now announced a collaboration with University College London to advance development of stem cell-based therapies for age-related macular degeneration (AMD). The London Project to Cure Blindness, led by Professor Pete Coffey (UCL Institute of Ophthalmology), is involved in producing a cell replacement therapy from human embryonic cells; a therapy which it aims to introduce into clinics by 2011. The goal is to replace cells essential for “seeing” lost through disease at the back of the eye. The UCL–Pfizer collaboration will accelerate the research process by bringing together the pioneering work of UCL’s researchers in the field of cell-based therapies and Pfizer’s expertise in design and delivery of therapeutics.

Under the terms of the agreement, Pfizer will provide funding to UCL to enable research into the development of stem cell-based therapies for AMD as well as other retinal diseases. Pfizer will also contribute expertise in the design and execution of clinical studies, interaction with global regulators, and in product manufacturing techniques. After the completion of preclinical safety studies, Pfizer will have the option to conduct clinical trials to determine efficacy of treatment and commercialize any resulting product.

Pfizer also recently signed deal with WARF for rights to human embryonic stem (hES) cells for dev of new drug therapies

One of the topics of discussion among those of us trying to lead the charge in commercializing cell therapies is the lack of experienced executive leadership at the helm of many cell therapy companies. Novocell, Inc, as it has done before on several fronts, is leading by example by hiring a seasoned biotech executive as its new President & CEO to replace Alan Lewis who went to lead the JDRF.

Novocell, Inc. recently announced the appointment of John West as President, Chief Executive Officer

“Novocell addresses one of the largest commercial and medical opportunities in stem-cell-derived therapeutics, and its team is increasingly recognized for its scientific and IP leadership,” said Mr. West. “I look forward to working with Novocell through clinical development and market launch and to growing a major new business.”

West, former CEO of Solexa, Inc. (NASDAQ:SLXA – News), brings more than 27 years of experience building profitable businesses from transformational technologies in the life sciences industry. Mr. West served as Chief Executive Officer of Solexa from 2004 until the company’s acquisition in 2007. When Mr. West joined Solexa, it was a private venture backed company with a radically different biochemistry and molecular biology for DNA sequencing. During Mr. West’s tenure, the company became public through a reverse merger, raised almost $100M and launched its first commercial product. This product lowered DNA sequencing costs over 100-fold, achieved almost $100M revenue in its first full year and became the dominant system for genome-scale genetic research. Mr. West led sale of the company in 2007 to Illumina, Inc (ILMN) for over $600M, and the business market cap subsequently exceeded $1B. Prior to Solexa, Mr. West served as VP of DNA Platforms, approximately a $1B business, at Applied Biosystems (ABI) (now Life Technologies). Mr. West’s responsibilities included the company’s businesses in DNA sequencing, preparative and real-time PCR, DNA synthesis and arrays. Prior to joining ABI, Mr. West was President of Princeton Instruments, a private company with transformational technology for low light imaging and spectroscopy. During Mr. West’s tenure, the company grew over 10 times in revenue, with much of the growth leveraging advances in cell biology. The company was sold to Roper Industries (NYSE:ROP – News), where Mr. West continued as subsidiary President. Mr. West holds B.S. and M.S. degrees in engineering from MIT, and an M.B.A. in finance from the University of Pennsylvania’s Wharton School.

Advanced Cell Technology, Inc. (Advanced Cell, ACT) (OTC: ACTC) and Korea-based CHA Bio & Diostech Co., Ltd. (CHA Bio), formerly known as CHA Biotech, Co., Ltd. and whose shares are publicly traded on KOSDAQ, announced that the parties have entered into a licensing agreement under which Advanced Cell will license its proprietary “single blastomere technology,” which has the potential to generate stable cell lines, including retinal pigment epithelium (RPE) cells for the treatment of diseases of the eye, to CHA Bio for development and commercialization exclusively in Korea. ACT received an undisclosed up-front license fee.

At this year’s ISCT conference, Invitrogen, a division of Life Technologies (NASDAQ:LIFE), announced a new technology to separate undifferentiated stem cells from those that are differentiated by utilizing magnetic beads that latch onto a common marker on embryonic and induced pluripotent stem cells, which are not considered as suitable for transplantation as those which are differentiated because of the potential of unregulated cell growth, removing them from a culture in less than 45 minutes. This leaves behind highly pure and differentiated cells that are unaffected by the process.

Histogen Aesthetics, a division of Histogen focused on providing unique, clinically proven, human skin cell-derived products for aesthetics medicine, has announced the launch of the ReGenica™ Rejuvenation System for anti-aging and post-resurfacing.

Histogen Aesthetics utilizes a proprietary manufacturing process in which newborn dermal fibroblast cells are grown on beads in controlled bioreactors that maintain an embryonic-like environment, including low oxygen and low gravity conditions. During this process, the cells secrete growth factors such as Keratinocyte Growth Factor and Vascular Endothelial Growth Factor, and soluble extracellular matrix proteins such as collagens, laminin and decorin, which are associated with skin renewal and scarless healing. The resulting product is ReGenica, a complex made up of the naturally produced cell signaling materials and embryonic-like proteins which support the epidermal stem cells that renew skin.

Stem cell therapy faces more scrutiny in China but regulations remain unclear for companies that supply treatments.

Hemogenix, Inc. is stepping up the heat a little in its competitive battle with Stem Cell Technologies, Inc. over the preferred assay method for stem cell quality control and potency. Hemogenix recently sent out an email and posted a statement on the homepage of its website saying “It has taken Stem Cell Technologies 6 years to acknowledge one of the basic concepts of the HALO Platform: By counting undifferentiated colonies at 7 days, they are actually counting clusters of “proliferation units” which can, in turn, be measured using ATP without any manual enumeration of colonies at 7 days. “

MISCELLANEA

FDA CBER’s Cellular, Tissue and Gene Therapies Advisory Committee held a meeting over the last couple day. On May 14 in the morning, in open session, the Committee was scheduled to discuss the potential for Chlamydia trachomatis and Neisseria gonorrhea transmission by human cells, tissues, and cellular and tissue-based products (HCT/Ps) that are recovered from the reproductive system or gestational tissues (e.g., amnionic membrane and placenta, cells recovered from menstrual blood, foreskin, placental/umbilical cord blood derived cell products), or other sources. In the afternoon, in open session, the Committee will discuss animal models for porcine xenotransplantation products intended to treat Type 1 diabetes or acute liver failure. On May 15, in open session, the Committee intended to: (1) Receive an update on Guidance documents from the Office of Cellular, Tissue and Gene Therapies, Center for Biologics Evaluation and Research and the Center for Veterinary Medicine and (2) discuss clinical issues related to the FDA draft guidance “Preparation of IDEs and INDs for Products Intended to Repair or Replace Knee
Cartilage.”

FDA intends to make background material available to the public no later than 2 business days before the meeting. If FDA is unable to post the background material on its Web site prior to the
meeting, the background material will be made publicly available at the location of the advisory committee meeting, and the background material will be posted on FDA’s Web site after the meeting. Meeting material is available online here.

BrightTalk recently hosted a stem cell webcast summit including presentation by ISCO – check it out here.

Sign-off

So with that I’m easing back in. As mentioned, I’ll try to back fill any news I missed and get back on schedule. Until then… ciao.

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Here is a listing of the corporate tutorial and symposia sessions being held at the International Society for Cellular Therapy conference Sunday-Wednesday in San Diego. For more information see www.celltherapy.org.

	ISCT 2009 Corporate Tutorial and Symposium Listing

Tuesday May 5, 2009
Time: 12:30pm – 1:30pm / Nautilus 3


BioLife Solutions Inc.

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Dendreon Corporation (Nasdaq: DNDN) will host a conference call tomorrow, Tuesday, April 14, 2009, at 9:00 AM ET (6:00 AM PT) to review the outcome of the FINAL analysis of its IMPACT (IMmunotherapy for Prostate AdenoCarcinoma Treatment, also known as D9902B) clinical trial of PROVENGE(R) (sipuleucel-T), the Company’s investigational active cellular immunotherapy for the treatment of advanced prostate cancer.

Those interested may access the call with the following information:

  Time:     9:00 AM ET/6:00 AM PT  Date:     April 14, 2009  Dial-in:  1-877-419-6594 (domestic) or +1-719-325-4855 (international)  Webcast:  www.dendreon.com (homepage and investor relations section

A recorded rebroadcast will be available for interested parties unable to participate in the live conference call by dialing 888-203-1112 or 719-457-0820 for international callers; the conference ID number is 8182435. The replay will be available from 12:00 pm ET on April 14, 2009 until midnight ET on April 16, 2009.

In addition the webcast will be archived for on-demand listening for 30 days at www.dendreon.com.

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Here we are in April 2009. The much newly anticipated date when we expect the Dendreon saga to head toward a climax. Few people know the Dendreon story better then Xconomy journalist, Luke Timmerman who does an outstanding job of summarizing the saga and stakes in Dendreon’s immiment Provenge gamble. Indeed tomorrow is the beginning of what we now anticipate will be the final chapter in this epic sage. Tomorrow (at 9am EDT), Dendreon will discuss the final results from their phase III IMPACT trial of Provenge for prostate cancer (call details here).

Here are a couple random bits to kick us off:

• According to a recent statement by the high-profile VC Steve Burrill, $5M in VC money used to buy 30-50% of a company; now it buys 90%.

• GEN’s editor in chief, John Sterling has included “Stem Cells: Translating Exciting Preclinical Data into Human Clinical Trials (Translational Medicine)” as one of his top-10 session picks for the upcoming 2009 BIO International Convention.

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Not settling with organizing doctors against the FDA with his “American Stem Cell Therapy Association (ASCTA)” (see my previous blog comments), Dr. Christopher “the renegade” Centeno is now inciting patients to oppose the “FDA’s position that the patient’s own adult stem cells are drugs and should be regulated as such.” (Click here for the press release.)

To facilitate patient activism he has launched a patient web-site, safestemcells.org, to drive the activities and opinions of patients in what he’s calling the Safe Stem Cells NOW! movement. The Stem Cells Now! movement’s goal? “To inform patients and physicians that their ability to access safe stem cell treatment is being heavily restricted by pharmaceutical industry agendas and by the FDA.”

He has also recruited the enthusiasm of Barbara Hanson, co-founder of stemcellpioneers.com, who is quoted as saying:

“Adult stem cells are cells from our own body. They are very safe. There are no moral or ethical issues. They are safer than taking aspirin and yet the FDA has classified our own stem cells as drugs that require regulation. This means that prolonged investigations, including lengthy clinical trials, will be required for each and every disease and application that adult stem cells could be used for. This could take years and years. It smells of big pharma to me and many others.”

For my other posts about the work of Dr. Centeno, see Regenexx vs the FDA 2009 and Cell therapy is not the practice of medicine.

FINANCIAL

Some people I talk to in the sector say they feel weirdly immune from the entire economic meltdown because the industry seems to be ticking along just fine in many ways continuing to be fueled by its own internal optimism and external enthusiasm for the promise of cell-based therapies…well that, and the still-growing amount of money being spent on the research side of the sector. Others, are certainly feeling the pinch. The dividing line may well be those who are trying to raise money and those who are not.

Having said that, here we go with reports of money being raised — all from non-US investors mind you. Proving that its economy is not down and out, the first two report of fundraises come from Down Under.

There’s no way I can start this first story any better then The Australian did in its March 12 report (that I only now just picked up now): “From the miracles-do-happen file comes this provident yarn of a $3.4 million market cap tiddler that has secured $12 million of funding for further development of its ovarian cancer drug, CVac.”

They’re talking, of course, about Prima BioMed Limited (ASX:PRR) which has been busy reinventing itself with new management and money since Biomira took a pass on its option to partner on CVac development more than a year ago. The company has been slowly bleeding money and management since. The company is still clearly on a low burn because I had to mine this information from anywhere but direct sources. The company itself has been very quiet about any of this.

The news is this: Prima Biomed has secured access to a $12-million funding facility from investment bank Fortrend Securities to help commercialize the company’s ovarian cancer treatment. The deal allows Prima to place shares with Fortrend as needed over the next three years.

Prima said it will use the cash to move through a phase IIb trial and towards a pivotal US registration trial of its dendritic cell-based ovarian cancer therapy, which the company says is designed to stimulate the body’s own immune system to attack cancer cells. The company said it now hopes to begin a US trial by mid-year, after the company reported positive feedback on its pre-investigational new drug meeting with the US Food and Drug Administration last year.

In a UK report about how stem cell innovation is at risk, the study authors from The University of Nottingham, funded by the Engineering and Physical Sciences Research Council (EPSRC), reports that the global cell therapy industry, reports that the global cell therapy industry:

“…now involves nearly 200 companies developing primary and secondary cell therapies, plus another 180 banking cord blood. In total the global cell therapy industry currently has sales of over $1 billion a year and a steady number of products are now reaching late stage clinical trials.”

Crystal Research Associates, LLC has issued an Executive Informational Overview® (EIO®) on Neuralstem, Inc. (CUR: NYSE-Alt)

CLINICAL

Amorcyte, Inc recently presented data at the American College of Cardiology (ACC) Annual Scientific Session from its Phase I clinical trial of AMR-001, the company’s lead product for the treatment of damaged heart muscle following acute myocardial infarction (AMI), that showed a significant relationship between cell dose and biologic effect. According to the company this is the first and only study to prospectively define a dose of a purified and potent autologous stem cell therapy (AMR-001) that resulted in a significant improvement in perfusion, a trend towards improved cardiac function and the potential to reduce subsequent adverse cardiac events following AMI. Emory University – one of the study sites – also issued its own press release on the data.

At the same meeting, TCA Cellular Therapy’s Medical Director Gabriel Lasala, M.D. presented preliminary results of an adult stem cell treatment for severe limb ischemia from its Phase I safety/efficacy clinical trial using a combination of the patient’s own endothelial progenitor cells (EPCs) and mesenchymyal stem cells (MSCs) obtained through bone marrow aspiration then mixed and infused into damaged veins.

MolMed S.p.A. (MLM.MI) announced that results obtained in the European multicentric Phase I/II study (TK007) of its TK therapy have been published in the April issue of the prestigious medical journal The Lancet Oncology. The article – Infusion of suicide gene-engineered donor lymphocytes after family haploidentical hemopoietic transplantation for leukemia: the TK007 phase I/II trial – gives insight into the outcome of the trial, conducted on 54 adult patients, that resulted in significant survival improvement of patients affected by high risk acute leukaemia receiving bone marrow transplants from a partially compatible family donor (haplo-transplants). In this context, the introduction of TK therapy allows the use of add-backs of donor T lymphocytes, that promote a rapid and wide immune reconstitution, abating transplant-related mortality and permitting long-term survival.

These trial results were, of course, already communicated to the market and included in MolMed’s Offering Circular and allowed MolMed to get authorisation to begin a Phase III randomised trial that started in Italy in Spring 2008, and will be expanded to other European clinical centres this year. The Phase III trial TK008 is pivotal for the registration of TK therapy, that could become among the very first cell therapies using genetically engineered cells to obtain marketing approval. MolMed’s partner for the Asian markets, Takara Bio Inc. (OTCPK:TKBIF), started clinical development of TK in Japan in October 2008, with a Phase I trial in relapsed leukaemia patients conducted at the National Cancer Center in Tokyo.

These breasts and slim waist are brought to you by Cytori Therapeutics, Inc. (NASDAQ: CYTX) and GE Healthcare. Available soon to women for only £6,500?

While Prima BioMed has been closing the deal on its new financing it has also apparently obtained permission from the Australian TGA’s Special Access to treat a patient with its CVac ovarian cancer treatment. The injection of the vaccine in ovarian cancer patients works as a postsurgery and post-chemotherapy maintenance therapy to delay relapse and control metastases. While the company is currently not in clinical trial in Australia and has not yet filed its IND for FDA approval in the U.S., the company has sought special exemption for a single-use treatment for what must be a very special patient.

Osiris Therapeutics, Inc. (NASDAQ:OSIR) announced the treatment of the first patient in a Phase II clinical trial evaluating Prochymal for the treatment of heart attacks.

COMMERCIAL

Further to my speculative post here last week, we’ve now learned that ULURU Inc. (NYSE Amex: ULU) has signed a non-binding offer letter to acquire York Pharma plc (”York”). York Pharma is a United Kingdom based skin care company with operations or distribution networks throughout Europe with an established revenue base. By way of reminder, the reason this is of interest here is that York has two cell therapy products on the UK market for the treatment of chronic wounds and burns: Myskin™ and Cryoskin™.

While the companies have not yet executed definitive documentation relating to any acquisition transaction and there’s no guarantee they will, Uluru is hoping potential benefits will significantly accelerate the maturation of ULURU into a commercially based company with a strong revenue base and positively position the company for more rapid growth both in the United States and Europe.ULURU Inc. is a specialty pharmaceutical company focused on the development of a portfolio of wound management and oral care products to provide patients and consumers with improved clinical outcomes through controlled delivery utilizing its innovative Nanoflex(TM) Aggregate technology and transmucosal delivery system

Novocell, Inc. announced that it has received U.S. Patent 7,510,876 with claims covering human definitive endoderm cells, an essential cell for generating not only pancreatic type cells, which Novocell is developing for use as a cell therapy for diabetes, but also other endoderm lineage-derived tissues and organs such as lungs, intestine, liver, thymus and thyroid.

Progenitor Cell Therapy LLC board member Robert A. Hamm promoted as COO of drug maker Biogen Idec.

Advanced Cell Technology, Inc. (OTCBB: ACTC.PK) could receive up to $1.9 million in fees as a result of a new licensing agreement with its Korean partner. ACT has agreed to license certain retinal pigment stem cell technology to CHA Bio & Diostech Co. Ltd. for development and commercialization exclusively in Korea. The two companies have a recently formed joint venture called “Stem Cell & Regenerative Medicine International” located in Worcester, MA and focused on the development of human blood cells. It is majority owned by CHA Bio and benefits from ACT exclusively licensing all of its hemangioblast technology to the joint venture.

If all milestones are met in this new collaboration focused on stem cell technology to treat a variety of eye diseases, ACT stands to earn $1.9 million in fees. CHA will pay all fees associated with clinical trials expected to take place in Korea. Meanwhile, ACT has applied to the U.S. Food and Drug Administration to begin clinical testing of its retinal pigment stem cell technology during the second half of the year.

Presumably to help soften the financial blow of its interrupted phase III trial of Prochymal for Crohn’s disease, Osiris Therapeutics, Inc. (NASDAQ:OSIR) has announced that it has agreed with NuVasive, Inc. (NASDAQ:NUVA) to accelerate transfer of the Osteocel business. Under the terms of amendments to the existing agreements between the parties, NuVasive will assume responsibility for Osteocel processing by April 10, 2009 and has removed contingencies applicable to $30 million of the $45 million in remaining milestone payments.

Osiris is now scheduled to receive $30 million in cash or NuVasive common stock in 3 schedule payments all before the end of September. The terms applicable to the remaining $15 million milestone payment are unchanged. This additional payment becomes due and payable when NuVasive achieves $35 million in cumulative Osteocel sales. NuVasis has projected $29 million in Osteocel sales in 2009.

To date Osiris has received from NuVasive $40 million in upfront and milestone payments. Effective April 10, Osiris will cease all operations associated with Osteocel processing. Concurrent with the amendments to the Asset Purchase and Manufacturing agreements, Osiris will transfer its Osteocel inventory to AlloSource, of Centennial, Co., which had been processing quantities of Osteocel for Osiris and has now agreed to produce Osteocel solely for NuVasive. NuVasive has entered into a separate outsourcing supply agreement with AlloSource for the continued manufacture of Osteocel.

Because of that deal, they are now able to layoff 80 people.

It looks like the ever well-tanned Burton Feinerman is back in control of his company Stem Cell Biotherapy which he at least appeared to lose temporarily to his former partner Casey Nabavi until Nabavi abandoned ship late last year to start a competing stemcell transplant company, Cellulogix. Now it looks like things are going to bet rough between the former partners. Stem Cell Biotherapy (”SCB”) has filed suit in Los Angeles County Superior Court against the Company’s Co-Founder and former President Casey Nabavi of Calabasas, California, for among other things conduct by Nabavi giving rise to patient claims against Nabavi that he had misrepresented himself as a medical doctor, practiced medicine without a license, supervised the injection of stem cells which caused some patients to become ill and personally advised patients how to manage these side effects. Nabavi/Cellulogix have offices/clinics in Los Angeles, Tampa, Montreal, Zona Rio (Mexico) and Istanbul. The SCB lawsuit also seeks to recover SCB funds in excess of $1.65 million that Navabi paid himself before leaving SCB, to recover assets including intellectual property belonging to SCB which Navabi took and used to start-up the new Cellulogix business, to prevent Nabavi from continuing to compete with SCB in contravention of the parties’ non-competition agreement and for SCB to recover ownership, the business and profits of Cellulogix as belonging to SCB not to Navabi as a result of Nabavi’s wrongful conduct and activities. A copy of the SCB lawsuit against Nabavi and Cellulogix can be viewed at the Company’s web site www.stemcellbiotherapy.com.

SCB is in the business of “assisting persons who desire to try stem cell therapy treatment for serious medical problems which have not responded to traditional medical treatments.” SCB uses medical clinics and specialized doctors in locations around the world where stem cell therapy is authorized to treat medical conditions such as spinal cord injury, ALS, Parkinsonism, Alzheimer’s, multiple sclerosis, autism, cerebral palsy, brain damage, heart disease, COPD, kidney diseases, eye diseases, diabetes, transverse myelitis, etc.

RESOURCES, EVENTS & MISCELLANEA

Regenerative Medicine Vol. 4, No. 2, March 2009 is now available online.

Stem cell scientist Dr. Robert Lanza, Chief Scientific Officer of Advanced Cell Technology has managed to find time away from changing the world of science and modern medicine to pen a book with astronomer Bob Berman on Biocentrism , a subject that challenges our traditional, outdated perceptions on life, time & space, and even death.

Sign-off

That’s all I got.

Thanks again to lab equipment supplier, Next Advance, for supporting this issue of the Cell Therapy Industry Hilites. They found me on Twitter, you can too. I’m @celltherapy.

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FDA has issued a new draft guidance entitled “Somatic Cell Therapy for Cardiac Disease“.

The guidance is intended to provide sponsors who are developing cellular therapies for the treatment of cardiac disease, with recommendations on the design of preclinical and clinical studies, and on the chemistry, manufacturing, and controls (CMC) information to include in an investigational new drug application (IND) for cardiac cellular therapy.

This guidance provides to sponsors developing cellular therapies for the treatment of cardiac disease with recommendations including, but not limited to, the following: (1) Design of preclinical and clinical studies; (2) information to submit on the product delivery system; and (3) the chemistry, manufacturing and controls information to include in an IND for cardiac cellular therapy. This guidance also includes regulatory considerations for the use of intravascular catheter delivery systems including recommendations regarding the information that sponsors should submit on the product’s delivery system.

The Background section of the guidance states as follows:

Cellular therapies for the treatment of cardiac disease generally meet the definition of “biological product” in section 351(i) of the Public Health Service Act (42 U.S.C. 262(i)), and are regulated by the Center for Biologics Evaluation and Research (CBER). Intravascular catheters and other drug and biologic delivery systems generally meet the definition of “device” under section 201(h) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321(h)).

FDA expects that these cellular therapies and their dedicated delivery systems would meet the definition of a combination product under 21 CFR 3.2(e), either by being co-packaged or, if marketed separately, by using labeling that indicates they are intended for use together. Based on available information, the somatic cellular therapy generally would provide the primary mode of action of the combination product and the lead center typically would be CBER in accordance with 21 CFR 3.4.

For a combination product, a single investigational application is generally sufficient. For cellular therapies and their dedicated delivery systems, this generally would be an IND. The IND application should contain the information as described in this guidance on the biological product and on the delivery system, along with any other information as required by the applicable regulations. CBER and CDRH intend to consult or collaborate on the IND review, as appropriate for the science and technology of the combination product.

For a combination product, one marketing application is also generally sufficient for FDA review and marketing authorization. However, sometimes two marketing applications may be necessary.

There has been much debate about how to interpret differing data and theories on the mechanism of action of cell therapies in cardiovascular disease. Clearly the agency is looking to set some standards in the design of these trials. I’ll let colleagues more qualified than I on the subject comment on what they’ve accomplished with the draft guidance.

Regenmedguru perhaps?

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A useful teaching image and an article that’s recommended reading:

Cell types available for regenerative medicine applications.

Click on image to view larger version.

Excerpted from: Stem cell bioprocessing: fundamentals and principles

Madsrk R Placzek, I-Ming Chung, Hugo M Macedo, Siti Ismail, Teresa Mortera Blanco, Mayasari Lim, Jae Min Cha, Iliana Fauzi, Yunyi Kang, David C.L Yeo, Chi Yip Joan Ma, Julia M Polak, Nicki Panoskaltsis† and Athanasios Mantalaris*

† Biological Systems Engineering Laboratory, Centre for Process Systems Engineering, Department of Chemical Engineering, Imperial College London
South Kensington Campus, London SW7 2AZ, UK

*Author for correspondence (a.mantalaris@imperial.ac.uk)

doi: 10.1098/?rsif.2008.0442 J. R. Soc. Interface 6 March 2009 vol. 6 no. 32 209-232

Abstract

In recent years, the potential of stem cell research for tissue engineering-based therapies and regenerative medicine clinical applications has become well established. In 2006, Chung pioneered the first entire organ transplant using adult stem cells and a scaffold for clinical evaluation. With this a new milestone was achieved, with seven patients with myelomeningocele receiving stem cell-derived bladder transplants resulting in substantial improvements in their quality of life. While a bladder is a relatively simple organ, the breakthrough highlights the incredible benefits that can be gained from the cross-disciplinary nature of tissue engineering and regenerative medicine (TERM) that encompasses stem cell research and stem cell bioprocessing.

Unquestionably, the development of bioprocess technologies for the transfer of the current laboratory-based practice of stem cell tissue culture to the clinic as therapeutics necessitates the application of engineering principles and practices to achieve control, reproducibility, automation, validation and safety of the process and the product. The successful translation will require contributions from fundamental research (from developmental biology to the ‘omics’ technologies and advances in immunology) and from existing industrial practice (biologics), especially on automation, quality assurance and regulation.

The timely development, integration and execution of various components will be critical—failures of the past (such as in the commercialization of skin equivalents) on marketing, pricing, production and advertising should not be repeated. This review aims to address the principles required for successful stem cell bioprocessing so that they can be applied deftly to clinical applications.

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Is another company with commercial cell therapy products about to be bought for a song?

York Pharma PLC (AIM:YRK) is a pharmaceutical Group established in 2003 specializing in the acquisition, development and commercialization of novel prescription dermatological products to market and supply branded prescription products to pharmaceutical wholesalers, hospitals and general practitioners within the field of dermatology.

University of Sheffield spin-out CellTran Ltd was incorporated in 2000 specializing in developing cell therapies to heal wounds. During its existence the company succeeded in bringing two cell therapy products into the UK market for the treatment of chronic wounds and burns: Myskin™ and Cryoskin™. CellTran majority shareholders were Biofusion plc, White Rose Technology Limited, The YFM Group, South Yorkshire Investment Fund, Partnerships UK and the Wellcome Trust.

In my December 12 post here on this blog, I reported the following:

One of the more important bits of news I’m late to the table for (announced at the end of October) is the acquisition of “certain of the assets and the continuing business of Celltran Limited (“Celltran”) from its administrators” by York Pharma plc (AIM: YRK) for what it describes – in the very undestated British way – a “compelling valuation”.

This seems an apt description when one learns that despite the fact that “approximately £15 million has been invested in the Celltran portfolio of products” to-date, York bought the company’s two commercial product plus “a rich pipeline of associated products and technologies” and the ongling business for – make sure you’re sitting down – “£70,000 plus the payment of royalties on future sales for a period of five years (at the greater of £100,000 (£20,000 per year) or 10% of future revenues generated by the products over such period)”.

The real reason this is such a compelling valuation is that Celltran had – and now York Pharma has – two cell therapies on the market (albeit only in the UK) in Myskin™ and Cryoskin™.

But the news does not end there. York also announced simultaneous to the acquisition that they had completed an institutional placing raising £510,000 (before expenses) to provide “additional working capital for the integration, operation and further development of the assets within York Pharma’s business.” York, established in 2003, describes itself as a pharmaceutical group with particular focus on dermatological products which makes the two cell therapy products fit well in their existing portfolio.

Now York Pharma is on the ropes.

It was reported today that “shares in the AIM-listed York Pharma were suspended from trading after the company said that it still hadn’t managed to secure any short term funding and as a result would miss the March 31 deadline to publish its annual results. Earlier this month York said it was in talks with two potential offerors and that those discussions included the provision of short term funding facilities. The company said it needed the cash to allow it to continue trading through the period needed to complete any formal offer.“

It was then reported later today that “one of the potential offerors has today entered into an agreement with the Company to provide the Company with a secured revolving Credit facility of up to US$1,000,000″ and that “drawdown of the full facility should allow the company to continue trading through the period needed to complete any formal offer“.

Now this begs the question: who is the suitor? One one hand this smacks of exactly the kind of move StemCells Inc has made more than once in the past. Would this fit with their other recent UK acquisition? With two products already on the market would this address STEM’s need for immediate revenue to fund its ongoing therapeutic development programs? While the answers might be “yes”, I doubt this kind of move is within STEM’s bandwidth given the ink is not yet even dry on the SCS deal (not sure it is even closed). If not STEM, then who?

Certainly this would be a fit with Advanced BioHealing’s portfolio or that of Karocell Tissue Engineering AB, FIDIA Advanced Biopolymers, or Forticell Bioscience (formerly Ortec International, Inc.). Would Genzyme or a pharma company pick this up? I have my doubts. Perhaps an Asian company like Japan Tissue Engineering Co., Ltd. (J-TEC)? It might also be quite compelling to merge this with Intercytex and create a company with several commercial cell therapy products and a rich pipeline of products.

It’s likely none of the above but it is fun to speculate. I’m sure we’ll find out in the next few days…

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This is my public service announcement for the week. ISCT continues to stack on the value to it’s annual meeting this year in San Diego with the recent announcement that ISCT, CIRM, and ISSCR are collaborating to bring a unique cell therapy translational development workshop to California.

DRAFT PROGRAM

7:00am – 7:50am Registration

7:50am – 8:00am Welcome + Introduction

8:00am – 10:00am Introduction to Translation of Stem Cell Therapies
Session chair: EJ Read MD

CIRM’s Initiatives for Translation of Stem Cell Therapies
Marie Csete, MD PhD (CIRM)

FDA’s Approach to Stem Cell Therapies
Kimberly Benton PhD (FDA/CBER/OCTGT)

IND Planning & Preparation for Stem Cell Therapies
EJ Read, MD (BSRI/UCSF-CTSI)

CMC Preparation & Pitfalls for Stem Cell Therapies
Darin Weber, PhD (Biologics Consulting Group)

Q&A/Panel Discussion

10:00am – 10:20am Break

10:20am – 11:50pm Late-Stage Translation: Cell Banking and GMP Manufacturing Models
Session chair: Shelly Heimfeld PhD

Cell Banking: FDA Perspective
Brenton McCright PhD (FDA/CBER/OCTGT)

Banking/Manufacturing Approach for Banked, Off-the-Shelf hESC-Derived Allogeneic Product (Oligodendrocytes, for spinal cord injury)
Anthony Davies, PhD (Geron)

Manufacturing Approach for a Banked, Off-the-Shelf Allogenic Fetal-Derived Product (CNS Stem Cells, for neurology applications)
Stewart Craig, PhD (StemCells Inc)

Manufacturing Approach for a Patient-Specific Allogeneic Expanded Cord Blood Progenitor Cell Product
Shelly Heimfeld, PhD (Fred Hutchinson Cancer Research Center)

Q&A / Panel Discussion

11:50pm – 12:50pm Lunch

12:50pm – 2:20pm Mid-Stage Translation: Assay Development and Preclinical Safety Testing
Session chair: Darin Weber PhD
FDA panelists: Theresa Chen PhD, Thomas Finn PhD

Assay Development for Stem Cell Products
Melissa Carpenter, PhD (Carpenter Group)

Preclinical Safety Program for Myeloid Progenitor Cell Product for Neutropenia and Radiation Injury
Holger Karsunky, PhD (Cellerant)

Preclinical Safety Program for hESC-Derived Products for Neurology Applications
Hans Keirstead, PhD (California Stem Cell and UC-Irvine)

Q&A / Panel Discussion

2:20pm – 3:20pm Mid-Stage Translation: Process Development and Product Characterization
Session Chair: Shelly Heimfeld PhD

FDA Perspective on Development & Characterization Issues
Thomas Finn, PhD (FDA/CBER/OCTGT)

Universal Donor Adult Stem Cell Product (for cardiovascular and other applications): Development and Characterization
Robert Deans, PhD (Athersys)

Gene-Modified Adult Stem Cell Product (for neurology applications): Development and Characterization
Casey Case, PhD (SanBio)

Q&A / Panel Discussion

3:20pm – 3:40pm Break

3:40pm – 4:20pm Early-Stage Translation: Challenges for Developing Combination Products
Session chair: Darin Weber PhD

Case study: Development of a Complex Combination Product (Device + Cells + Genetic manipulation)
B. Lynn Allen-Hoffman. PhD (Stratatech)

Q&A

4:20pm – 5:30pm Early-Stage Translation: Induced Pluripotent Stem Cells
Session chair: Marie Csete MD PhD

IPS cells in Amyotrophic Lateral Sclerosis
Evangelos Kiskinis, PhD (Harvard Stem Cell Institute)

IPS cells in Spinal Muscular Atrophy
Clive Svendsen, PhD (U of Wisconsin)

5:30pm – 5:40pm Wrap Up

5:45pm – 7:15pm Reception

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Further to my post on this topic back in September last year and ongoing discussions I have been having, I have decided to create a quick 4-question poll to get your opinion.

I am not representing anyone or any organization with this survey. I’m out on a limb on my own. I’m curious to see your response to this quick 4-question survey.

Click here to see the survey.

www.celltherapyblog.com hosted by www.celltherapygroup.com

There are some real, imminent stimulus funding opportunities related to cell therapy that offer up to $1 million in funding over 2 years for up to 200 projects all to be handed out quite quickly. If you’re interested, here is some info.

To cut right to the chase here’s the link:

Recovery Act Limited Competition: NIH Challenge Grants in Health and Science Research (RC1) — request for applications (RFA) number: RFA-OD-09-0003. Bethesda, MD: National Institutes of Health, March 4, 2009. (http://grants.nih.gov/grants/guide/rfa-files/RFA-OD-09-003.html)

The American Recovery and Reinvestment Act of 2009 (Recovery Act) (H.R. 1, S. 1 – PDF-1MB) is a Federal public law passed by the 111th United States Congress and signed into law by President Barack Obama on February 17, 2009.

As part of the Recovery Act, NIH has designated at least $200 million in FYs 2009 – 2010 for a new initiative called the NIH Challenge Grants in Health and Science Research, to fund 200 or more grants, contingent upon the submission of a sufficient number of scientifically meritorious applications.

The April 9 issue of NEJM (Volume 360:1479-1481) summarizes the program as follows:

The NIH also announced that it had designated “at least” $200 million of the stimulus money to fund 200 or more grants in specific challenge areas (comparative-effectiveness research, clinical research, genomics, information technology for processing health care data, regenerative medicine, stem-cell research, and nine others) that “focus on specific knowledge gaps, scientific opportunities, new technologies, data generation, or research methods that would benefit from an influx of funds.”

This program will support research on Challenge Topics which address specific scientific and health research challenges in biomedical and behavioral research that will benefit from significant 2-year jumpstart funds.

Challenge Areas, defined by the NIH, focus on specific knowledge gaps, scientific opportunities, new technologies, data generation, or research methods that would benefit from an influx of funds to quickly advance the area in significant ways. The research in these areas should have a high impact in biomedical or behavioral science and/or public health.

Links to high priority topics within the broad Challenge Areas that relate particularly to cell therapies include:

(06) Enabling Technologies
(07) Enhancing Clinical Trials
(11) Regenerative Medicine
(13) Smart Biomaterials – Theranostics
(14) Stem Cells
(15) Translational Science

I’ve scanned through and below are some of the funding high priority topics that I thought might be applicable and of interest here but it is certainly not exhaustive (in other words you should look for yourself):

06-DK-101* Development of cell-specific delivery systems for therapy and imaging. Develop non-viral strategies for cell-specific delivery of pathway-interactors and molecular probes. These new molecular complexes could allow delivery of cell-penetrating agents for the study of disease pathways, the imaging of tissue mass and disease progression, or the development of tissue-specific therapeutics. Contact: Dr. Olivier Blondel, 301-451-7334, blondelol@mail.nih.gov; NIAAA Contact: Dr. Samir Zakhari, 301-443-0799, szakhari@mail.nih.gov; Contact: Dr. Joan McGowan, 301-594-5055,
NIAMShelp-NIHChallengeGrants@mail.nih.gov

06-EB-102* Development of biomedical technologies and systems. Focus areas include: (1) providing immediate diagnostic information for multiple conditions at the point-of-care; (2) a robust, consistently accurate glucose sensor with extended functional lifetime, improved accuracy and low variability of readings; or (3) low cost diagnostic or therapeutic systems. Also, development of such devices engineered to work in low resource settings. Contact: Dr. William Heetderks, 301 451-6771, heetderw@mail.nih.gov

11-DC-101* Hair Cell Regeneration and Maintenance. One common cause of hearing impairment in humans is the progressive loss of the auditory transduction cells, or hair cells, in the inner ear. A similar loss of motion transduction cells in the vestibular organ is a probable cause of balance disorders. Once lost, these cells cannot be spontaneously regenerated in mammals. The Challenge is to develop and validate methods to regenerate and maintain hair cells in animal model systems with the eventual goal of successful translation to human treatments. Contact: Dr. Nancy Freeman, 301-402-3458, freemann@nidcd.nih.gov

11-EB-101* Vascular networks in engineered tissues. Research on the design, optimization, and formation of a complete vascular network capable of delivering oxygen and nutrients and removing waste products in engineered tissues (i.e., vascularization of engineered tissue constructs). Dr. Rosemarie Hunziker, 301-451-1609, hunzikerr@mail.nih.gov

11-HL-101* Develop cell-based therapies for cardiovascular, lung, and blood diseases. Cell-based therapies for cardiovascular, lung, and blood diseases offer a new paradigm for advancing and transforming patient care. Translational and early-phase clinical research has demonstrated that cell-based therapies may improve left ventricular function, reduce myocardial ischemia, and lead to improved lung function. Reconstitution of normal hematopoeisis using modified stem cell graft sources has great potential for treating specific genetic blood disorders. However, a number of significant challenges and barriers must be overcome to move the field forward toward broad clinical application. We encourage further research to determine the characteristics of the most promising target patient population, the best cell type and number of cells to use, the optimal methods and timing of delivery, and other preclinical parameters. Contact: Dr. Sonia Skarlatos, 301-435-0477, skarlats@nhlbi.nih.gov

14-EY-101* Development of stem cell treatment for degenerative diseases of the eye. The restorative properties of stem cells hold the promise in the treatment of degenerative eye diseases such as macular degeneration, diabetic retinopathy, retinitis pigmentosa and glaucoma, and diseases of the ocular surfaces. There is a need for the identification of biomarkers that can define stem cells and the end-stage cells, as well as reproducible protocols for the generation and purification of viable terminally differentiated cells. Contact: Dr. Grace Shen, 301-451-2020, sheng@mail.nih.gov

15-RR-101* Applied translational technology development. This program will support two-year applied translational projects to move advanced technologies from the prototype stage into the clinic. Novel, cost-effective tools for clinical care or clinical research will be modified, hardened, and tested. Interdisciplinary teams of technology developers, basic researchers and clinicians will address scientific and engineering problems associated with clinical applications of new technologies. Contact: Dr. Douglas Sheeley, 301-594-9762, sheeleyd@mail.nih.gov; NIDA Contact: Dr. Kris Bough, 301-443-9800, boughk@mail.nih.gov

__

The broader Omnibus of Broad Challenge Areas and Specific Topics has many more challenge topics including the following I thought were potentially applicable:

06-EB-108 Imaging of Drug and Gene Delivery Systems. Three major challenges in the field of drug and gene delivery are: targeting of therapies to tissues, cells, and intracellular compartments; monitoring exactly where the therapies localize after administration; and determining if the agents delivered are doing what they were intended to do. We encourage proposals to develop multifunctional systems that: 1) are capable of targeted delivery of drugs, proteins, genes, or nucleic acids to specific cells, or compartments within cells in vivo; and 2) possess imaging capabilities to track delivery, assess function, and determine therapeutic efficacy. Contact: Dr. Lori Henderson, 301-451-4778, hendersonlori@mail.nih.gov

06-HL-103 Develop new imaging methodologies to track cells and measure accurately the chemical activities of enzymes and metabolites in intact cells, tissues, and organisms to improve basic understanding of cellular interactions, biological pathways, and their regulation. An improved ability to track cells in vivo will enhance our understanding of homing, engraftment, cell differentiation, and pathogenesis resulting from abnormal cells trafficking. Understanding the components and kinetics involved in biochemical reactions is key to evaluating and predicting the response of intact organisms to physiological and pathophysiological challenges and drug responses. Although our knowledge of the identity and quantity of proteins and complexes associated with reaction pathways in health and disease continues to advance, direct methods for imaging those reactions in intact systems are lacking. Development of appropriate tools to track cells, image the microvasculature, and image chemical activity in intact systems in real time will have broad applicability to many heart diseases, including myocardial ischemia and reperfusion injury, heart failure, and arrhythmias and lung diseases such as COPD, asthma, pulmonary hypertension, and sleep apnea. Similarly, new non-invasive cellular imaging modalities, capable of differentiating between normal and pathological states, would increase our understanding of the role of the microvasculature in sickle cell disease and thrombotic disorders. Contact: Dr. Lisa Schwartz Longacre, 301-402-5826, schwartzlongal@mail.nih.gov

11-DK-104 Use of Hematopoietic Stem Cells (HSC) to regenerate or repair mesenchymal tissues. Examples include: Develop and validate methods and reagents that induce HSCs to develop or trans-differentiate into different mesenchymal cell and tissue types; Develop and validate methods and reagents that allow HSCs to be propagated in vitro without loss of self-renewal potential. Contact: Dr. Terry Bishop, 301-594-7726, bishopt@mail.nih.gov

11-EB-105 Advanced Imaging Systems for Tissue Engineering. The ability to monitor complex cell-cell and cell-matrix interactions in engineered tissues in vitro and in vivo is critically important. The imaging needs to be functional—able to assess meaningful changes non-destructively and non-invasively; intrinsic—using inherent signatures of normal biological processes (e.g. intermediates of energy metabolism, conformationally-based changes in light scattering); and dynamic—monitoring events as they are occurring. Proposals to develop tools for characterizing engineered tissues in vitro and in vivo are encouraged. Contact: Dr. Rosemarie Hunziker, 301-451-1609, hunzikerr@mail.nih.gov

11-EB-106 Technologies for Expanding Stem Cells and Producing Engineered Tissue. Tissue engineering and regenerative medicine is a rapidly evolving field, but current production and manufacturing technologies are confined to the laboratory scale and grossly inadequate to ensure sufficient quantity and quality on an industrial scale. New measurement tools, and engineering methods and design principles that can model, monitor, and influence the interaction of cells and their environment at the molecular and organelle level are urgently needed. Projects are sought to develop scaleable bioreactors to precisely control the chemical and mechanical environment for functional 3D tissue growth or for rapidly expanding stem cells; quantitative, non-invasive tools to monitor structure, composition, quorum sensing, and function of heterogeneous tissues in real time; and technologies for preservation, sterilization, packaging, transport, and ensuring cell and tissue health and phenotypic stability. Contact: Dr. Albert Lee, 301-451-4781, alee@mail.nih.gov

11-GM-101 Establishment of regenerative capabilities. Development of approaches and technologies to establish regenerative capabilities in adult cells to repair or replace damaged tissues and organs in situ and to improve wound healing and reduce scarring in human and animal models. Contacts: Dr. Susan Haynes, 301-594-0943, hayness@nigms.nih.gov, Dr. Richard Ikeda, 301-594-3827, ikedar@nigms.nih.gov

13-DK-104 Islet encapsulation. Development of novel islet encapsulation technologies/biomaterials for the optimization of a bioartificial pancreas. Contact: Dr. Guillermo Arreaza, 301-594-4724, arreazag@mail.nih.gov.

13-EB-102 Non-viral Gene Delivery Systems. The major barrier to success of gene therapy in the clinic is the lack of safe and efficient DNA delivery methods. Although viral delivery systems allow efficient and long-term gene expression, they generally do not permit targeted delivery to particular cells and tissues and pose problems with regard to immune response. Proposals are invited to develop novel, safe, and targeted, synthetic or viral mimetic vectors for gene delivery including quantitative studies that relate their structure and properties to function. Contact: Dr. Lori Henderson, 301-451-4778, hendersonlori@mail.nih.gov

14-DE-103 Enhancing Human Embryonic Stem (ES) Cell Culture Systems. Cell differentiation and tissue morphogenesis during normal development is guided by the highly orchestrated temporal, spatial and combinatorial action of multiple of ligands, signaling pathways, transcription factors, and extracellular matrices. In light of this tremendous complexity, the existing human ES cell in vitro culture systems lack appropriate sophistication thus necessitating the need for strategies to better mimic normal developmental processes. Recent progress in the fields of bioengineering, nanotechnology, biomaterials and bioimaging offer a wealth of tools that can lend tight control of the multiple parameters needed to improve the existing human ES culture systems. Goal: Integration of engineering disciplines with developmental biology and with ES cell technology for deriving a new generation of human ES cell culture protocols that will facilitate the application of ES cell-based therapies for the treatment of a multitude of human tissue degenerative diseases and trauma, including those of oral and craniofacial complex. Contact: Dr. Nadya Lumelsky, 301-594-7703, Nadya.Lumelsky@nih.gov

Finally, here is some other key data and links.

Challenge Award Resources

• 2009 Funding Opportunity Announcement (RFA-0D-09-003)
• NIH Institute & Center (IC) Web Sites
• Frequently Asked Questions – NIH Challenge Grants
• Challenge Awards Review Timeline

Some key timeline dates:
Application Due Date(s): April 27, 2009
Peer Review Date(s): June/July 2009
Council Review Date(s): August 2009
Earliest Anticipated Start Date(s): September 30, 2009

Budget requests should be commensurate with project needs up to a two-year project period. The requested budget may not exceed $500,000 total costs per year for a maximum of $1,000,000 total costs over a two-year project period.

Thanks to Bob Speziale from Invetech to pointing this out to me and thus…to you. Good luck to you all.

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