Cell Therapy Industry HiLites 2008-12-19

Ok so it's almost not Friday anymore even by my Pacific Time Zone but I promised to try to do this every Friday and so here I am. I will not be doing a HiLites next Friday however. I'm taking a break for the holidays.

For the week before Christmas this was one busy week!

I'll start this week's HiLites with a bit of a focus on Bioheart, Inc. (Nasdaq:BHRT). The company has been busy this week reinventing itself - just how much remains to be seen. As followers of the industry will recall, Bioheart had a disappointing IPO earlier in the year but was able to raise ~$1.8M in a private placement in October. This, I suspect, is not much more than survival money as they are financing a 330-patient phase II/III trial in US and Europe.

So the company's announcement this week came as no surprise that it intends intends o spin out or sell off its interest in several non-core technology platforms including:
- Biopace -- A biological pacemaker.
- MyoValve -- A cell seeding method for repairing and building biological heart valves.
- EndoCell -- A system for bedside preparation of adipose tissue for delivery of endothelial progenitor cells to the adventitia of coronary arteries for prevention of restenosis following
balloon angioplasty, stenting or atherectomy.
- AortaCel -- Cell compositions and delivery systems for repairing aortic aneurysms or for reinforcing the neck area in aortas repaired with an endovascular stent graft.

In addition, Bioheart is seeking a strategic partner for the development of its bi-ventricular pacemaker technology, called MyoStim, which utilizes a patented electrical stimulation software program and an additional pacemaker lead to enhance cell transplantation.

Understandably Bioheart is doing this in order to intensify its strategic focus on the treatment of patients suffering from heart failure. Interestingly, however, in their press release Bioheart made no mention of their cell therapy saying rather that Company is strategically focused on commercializing patented technologies for reducing and repairing heart muscle damage caused by heart attacks as well as marketing advanced heart failure monitoring devices including the Bioheart 3370 Heart Failure Monitor and the Bioheart-Monebo CardioBelt(tm) ECG Acquisition Device.

Then yesterday Bioheart announced it had had signed a deal with Life Technologies Corporation (Nasdaq:LIFE) (the new combined Invitrogen-Applied Biosystems entity) which provided Life the global distribution to Bioheart's myoblast cell-based research products to life science researchers. The deal is intended to "expand the number of therapeutic applications under development with this type of cell" but again no mention of Bioheart's own trial or product.

All of which leads to at least a couple questions we hope Bioheart will soon answer. Firstly, is the company positioning itself away from its lead product MyoCell®? Secondly, the deal with Life Technologies was described as a "distribution and OEM agreeement" but while there was discussion about the distribution aspects of the deal, there was no description of the OEM part. Given that neither company has any notable capacity or expertise in producing clinical-grade cells will this only encompass research-grade cells or are there other plans here not being discussed?

I'll move on to other news of the week.

In a move that will certainly enhance his legacy on his way out the door, Alan Lewis announced that Novocell, Inc. has entered into a non-exclusive drug discovery collaboration with Pfizer which gives Pfizer access to Novocell’s proprietary pancreatic progenitor cells derived from human embryonic stem (hES) cells. This appears to be an open-platform type of agreement (limited for now to 2 years). Novocell will receive an upfront payment, research funding, additional amounts payable upon the achievement of certain technical milestones, and payments relating to the sale by Pfizer of any exclusive therapeutic discovered as a result of the collaboration.

Novocell has shown it can coax human embryonic stem cells to become fully functioning pancreatic beta cells that secrete insulin in mice but about 15 percent of the animals got teratomas, a type of tumor. This, the company will have to learn to prevent or at least control before it gets approval to go to human clinical trials. For now, as Xconomy's Luke Timmerman says, "Novocell can take some comfort knowing that some of the deepest pockets in the pharmaceutical industry are shelling out at least a little spare change to help it crack daunting challenges like that."

BioLife Solutions Inc. (OTCBB: BLFS) announced that it has completed an initial series of small animal safety studies. The studies evaluated injections of HypoThermosol, CryoStor, or control phosphate buffered saline (PBS) into healthy rodents. The study was designed to mimic human clinical applications where stem cells isolated from cord or peripheral blood are re-suspended in a carrier solution and administered intravenously to treat patients suffering from a variety of diseases and disorders including leukemia, anemia, lymphoma, myeloma, and other cancers.
The results of these studies demonstrate- the Company claims - that infusion of HypoThermosol and CryoStor present no safety risk within the parameters of this two-stage evaluation in a rodent model. Data to be published and/or presented soon.

Avita Medical Ltd (ASX: AVH) says the French Ministry of Health is funding a 200 patient medico-economics study on the impact of Recell on burn wound healing. Avita said that the first patients were enrolled and had been treated in the study which was part of a French program “to advance the implementation of innovative technologies”. Avita said the primary goal was to demonstrate the medical effectiveness and economic benefits of the Recell technology to the hospital and health care system in the treatment of burns and wounds.

Recell, already commercially available in Australia, is a single-use medical device for harvesting autologous skin cells. Developed as an 'off the shelf' kit, ReCell enables a thin split thickness biopsy, taken at the time of procedure, to be processed into an immediate cell population for delivery onto the wound surface. Once processed, the cell suspension is available for immediate use and can cover a wound up to 80 times the area of the donor biopsy. ReCell enables the delivery of keratinocytes, melanocytes, fibroblasts and Langerhans cells harvested from the epidermal-dermal junction for application onto a wound surface in order to promote effective wound healing.

Pluristem Therapeutics Inc. (NasdaqCM:PSTI) (DAX:PJT) filed a European Investigational Medicinal Product Dossier (IMPD) to begin clinical trials of its placental-derived adherent stromal cell product, PLX - PAD, an allogeneic cell therapy, for critical limb ischemia. The company filed the IMPD application with the Paul Ehrlich Institute (PEI), the German competent authority in the European Union (EU). An IMPD is a harmonized procedure for the authorization to perform a clinical study in any one of the EU Member States. An IMPD is requested whenever the performance of a clinical study in any one of the EU Member States is intended, and it is similar to an Investigational New Drug (IND) Application that would be filed for the performance of a clinical study in the United States. Assuming approval of the IMPD by this authority, Pluristem said it plans to initiate the dose ranging clinical trial during the second quarter of 2009 at two sites in Berlin, Germany

Amgen lobbied this week for personalized medicine by presenting to the FDA the argument that one of its drugs should be used by just a subgroup of patients with colorectal cancer who appear to be most likely to benefit from it.

NeuralStem filed an IND to use its neural stem cell technology in a trial for Lou Gehrig’s disease in what it described as the first ALS trial using stem cells.

Progenitor Cell Therapy has brought in a new CFO with over 21 years of experience in the life sciences industry and fundraising. This will undoubtedly help them raise the funds needed for their continued US and European expansion plans.

StemCells, Inc (NASDAQ: STEM), which already has a trial underway for Batten disease, just received FDA approval to start a trial for Pelizaeus-Merzbacher Disease (PMD), also fatal brain disorder that affects mainly young children. The mechanism of the potential Batten disease therapy is to establish healthy neural cells that can help a patient’s own cells clear out some toxic garbage that builds up in the disease, the mechanism for PMD is to boost myelinization of neurons. StemCells uses cells originally derived from fetal tissue.

Although this news will be old to some I discovered this week Arteriocyte's announcement from November 10 that it had been awarded the DARPA Blood Pharming award to the tune of $1,950,000 which presumably it has to share with collaborators at Johns Hopkins University, The Ohio State University and INSERM, Paris. While this seems like a sizeably juicy award, the US Military's Defense Advanced Research Projects Agency (DARPA) has issued a tall order. DARPA wants a self-contained device small enough (≤47 ft3) to go into the military field and create at least 100 units of universal blood (i.e., can be transfused into anyone regardless of blood type) per week for eight weeks. The key ingredient to Arteriocyte's proposal and the company's Nanofiber Based System (NANEX) technology is umbilical cord blood stem cells.

While technically not a cell therapy play, both these players are notable enough in the cell-as-tools sector that we thought it worth noting that VistaGen Therapeutics has signed a deal with Wisconsin Alumni Research Foundation (WARF) to license WARF's human embryonic stem cell patents for the development and commercialization of stem cell-based research tools.

Winning this week's award for the press release with no news, is the annoucement from Advanced Cell Technology, Inc.(Other OTC: ACTC.PK) that "its technology platform, which utilizes a single cell biopsy that does not destroy the embryo, is well positioned to receive Federal funding under the new administration led by President-Elect Barrack Obama."

They made up for it the next day, however, by releasing news of new funding. Demonstrating, once again, their tenacious survivability, ACT announced it had licensed a "non-core technology" to one of its creditors, Ireland-based Transition Holdings, Inc, for $2.5 million - comprised of the extinguishment of $1.5 million of debt and an additional funding commitment of $1 million. The Company expects to apply the proceeds it receives in the future towards its retinal pigment epithelium (RPE) cells program.

Cytori has now launched a a 30-person clinical trial using adipose (fat) stem cells for chronic radiation induced injury.

Life Technologies announced its CIRM award will be used to develop human stem cell models of neurodegenerative diseases to advance drug development. The company intends to use human embryonic stem cells to develop new models of Lou Gehrig's Disease and other neurodegenerative diseases.

Inno Bio Diagnostics Sdn Bhd (IBD), which specialises in cell-based diagnostics and regenerative medicine, is investing RM4.58 million (~$1.3M) to set up a cell therapy centre at the Universiti Kebangsaan Malaysia Medical Centre (UKMMC) in Kuala Lumpur, Malaysia. IBD, a wholly-owned subsidiary of Inno Bio Ventures Sdn Bhd, aims to create and develop business opportunities in stem cell technology in the area of cell-based diagnostics and therapy. The cell therapy centre, which is expected to start operations next year, will be jointly managed by IBD and UKMMC to develop human hepatocyte-like cells from stem cells that are derived from embryonic, bone marrow, mesenchymal and adipose tissues. The human hepatocyte-like cells can be used for in vitro assays for screening and testing potential drugs for the pharmaceutical and nutraceutical industries. According to Ahmad Zaharudin, the company is projecting a revenue of RM15 million to be generated from the product, knowledge transfer and licensing of technology as outcome of the partnership.

Genzyme Corporation announced that the U.S. Food and Drug Administration has granted marketing approval for Mozobil(TM) (plerixafor injection), a drug intended to be used in combination with granulocyte-colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells to the bloodstream for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). The product has also been granted orphan drug designation. Genzyme has submitted an application in Europe for approval of Mozobil and expects approval of the product in the second half of 2009. Genzyme recently filed applications in Australia and Brazil, and additional global applications in up to 60 countries are planned. Mozobil has received orphan drug designation in Mexico which allows the product to be commercialized in the country upon U.S. approval. Genzyme believes that Mozobil may have broad application outside the current indication. Early preclinical and clinical investigations are already underway to explore additional therapeutic indications for Mozobil, including mobilization of hematopoietic stem cells in allogeneic stem cell transplants and tumor sensitization in oncology/hematology treatments such as adult myeloid leukemia.

And finally... it looks like there's a showdown shaping up in Colorado. As disucssed previously on this blog, in July FDA CBER's Mary Malarkey sent a warning letter to Dr. Christopher J. Centeno, Medical Director of Regenerative Sciences, Inc (RSI), doing business as Regenexx. On a recent visit to the Regenexx website, we see that they state the following:

"The Food & Drug Administration's (FDA) role is to regulate the sale and distribution of drugs, devices, biologics and combination products, but not how these products are used by physicians. The FDA does not approve surgical procedures. RSI conducts all surgical procedures within the State of Colorado. There are no interstate aspects to the procedures conducted by RSI that invoke FDA jurisdiction under the Public Health Service Act (PHSA), which requires an interstate nexus. Our surgical procedure involve the use of autologous stem cell therapies (ACTs) consisting of products or treatments incorporating the in vivo use of a patient's own stem cells, following, in certain circumstances, ex vivo manipulation or processing, for the prevention, or treatment of disease. The surgical procedures conducted by RSI including surgery and bone marrow transplants are not performed as part of any research intended for FDA approval of a product that is under the jurisdiction of the FDA. Therefore, the stem cell procedures conducted by RSI are not under the jurisdiction of the FDA. Rather, the procedures conducted by RSI are considered the "practice of medicine," and is left up to individual surgeons' judgment and experience and oversight by the Colorado Board of Medicine." [emphasis added]


And that ends the way I saw the cell therapy industry this week.... More HiLites to come in 2009! Happy holidays to one and all.

--Lee

Cell Therapy Industry HiLites 2008-12-12

Rumor is there was little in the way of cell therapy at the ASH meeting this year and the TERMIS meeting was mostly "basic research". I'd love to hear other reports. Maybe because of that, it seemed oddly slow on the cell therapy front this week. Despite that, we've got some interesting news to review.


This issue of Newseek had an article by David T. Scadden, M.D. and Anthony L. Komaroff, M.D. "Will Stem Cells Finally Deliver? Major breakthroughs are propelling the field. Science becomes medicine."

TiGenix secured grant support to deepen its pipeline. The company has been awarded a €1.81 million, or $2.41 million, grant to support its R&D efforts a meniscus repair program. The two-year program will focus on the further development and application of allogenic stem cells in combination with a biocompatible scaffold, the identification of biomarkers predictive for the quality of meniscus-like tissue, and establishing preclinical proof-of-principle for cellular repair of meniscus lesions.

The European registration procedure for its lead product, ChondroCelect®, is reportedly progressing. As this is the first cell based product submitted to the EMEA under the central registration procedure, some further documentation on the product and process validation processes was recently requested by the regulatory authorities. The company is apparently now compiling further information for submission, and expects the CHMP to issue an opinion on the marketing authorization for ChondroCelect in the first half of 2009. If approved, ChondroCelect will be the first cell-based product to receive a central marketing authorization for an advanced therapy medicinal product in Europe. The preparation of the Biologics License Application (BLA) to obtain product registration in the US is also reportedly progressing according to plan. The company intends to start the registration process with the US Food and Drug Administration (FDA) in the first half of 2009. (for a recent TiGenix update, click here).

Athersys received its third IND for MultiStem in less than a year with authorization to proceed on a phase I trial in the treatment of ischemic stroke.

CIRM grants were approved to 4 San Diego biotechs:

• $827,072 for Novocell to advance development of “an implantable device” to capture and retain pancreatic stem cells.
• $749,520 for a joint effort by Fluidigm of South San Francisco and StemGent, a Cambridge, MA, biotech with operations in San Diego, to develop a screening technology to help stem cell researchers “reverse engineer” skin cells into stem cells.
  
• $869,262 for an application by Invitrogen, now known as Life Technologies, for developing methods of modelling human neurodegenerative diseases in human embryonic stem cells.
• $906,629 for Vala Sciences to develop new and improved techniques for developing mature heart cells called cardiomyocyte cells from human embryonic stem cells.
  

Immunotherapy has certainly seen its share of failures but T-cell oriented therapies are not going away as they continue to attract funding by companies looking to avoid the difficulties that have sunk other efforts to commercialize immunotherapies. One such new company is Adaptimmune Ltd which recently spun out of MediGene AG to carry forward T cell receptor engineering with HIV as its initial target. The company's ex vivo approach sees a patients' own T cells harvested, those cells' receptors genetically enhanced for increased potency against certain infections or tumors in the manner of monoclonal antibody selection, and re-infused into the patient.

Osteotech authorized a stock buyback of up to $5 million.

Novocell announced it will collaborate with renowned stem cell researcher Shinya Yamanaka of Kyoto University to explore the creation of human islet cells from iPS cells. Common wisdom says Novocell has been in the lead in the race to a cell-based approach to diabetes therapy but they are not without competition. Earlier in the year giant Novo Nordisk did a deal with Cellartis and Lund University to create insulin-producing cells for diabetes. Novo Nordisk has been selling insulin since 1923 and knows the diabetes market well. Additionally, Geron announced a publication on its progress coaxing embryonic stem cells into what it calls islet-like clusters.

ERYtech Pharma announced the results of its phase II clinical trial. ERYtech Pharma, the specialty pharmaceuticals company developing red cell-based medicinal products, announces the results of its phase II clinical trial. GRASPALL 2005-1 was presented orally on the 8th December 2008 at the 50th Annual Meeting of the American Society of Hematology in San Francisco (USA). This study aimed to assess the efficacy and the safety of 3 doses of GRASPA®, a new formulation of L-asparaginase, given in frontline treatment for children and adults with
relapsed acute lymphoblastic leukemia (ALL).

In a December 3 press release and conference call ThermoGenesis announced it has reached an agreement with CEO William Osgood for his immediate resignation. This comes as a result of a clear disagreement between Osgood and Board regarding future directions of the company. A search for a new CEO will be launched. In the interim, the board has named Matthew T. Plavan, the Company’s Executive Vice President and Chief Financial Officer, as ThermoGenesis’ interim Chief Executive Officer. The company has announced its intention to reorganize, downsize, maximize, sideline its Vantus business, and dispose of the ThermoLine™ business yet this quarter.

BioLife Solutions was granted a European biopreservation patent expanding its IP related to technologies which minimize cell death during or resulting from cell preservation.

Chemokine Therapeutics Corp. (CTI.TO) filed Chapter 11 equivelant in Canada - a Proposal to Creditors under the federal Bankruptcy and Insolvency Act.

Stem Cell Therapy International Inc. announced the elimination of what it described as "major obstacles" previously blocking its merger with Histostem including the establishing of a relationship with a clinic in Mexico. The companies are apparently in the final stages of completing the merger to create AmStem International and begin creating revenue almost immediately presumably involving a new relationship with U.S. company, Cancun Stem Cell Clinic, Inc. (with its stem cell clinic in Cancun, Mexico) and Histostems cord blood banking operations.

MicroIslet Inc. is reorganizing its way through Chapter 11 with the help of new financing.

Pluristem received a $1.6M grant from the Office of Israel’s Chief Scientist. The non-dilutive funds will be designated to support the clinical trials of the Company as well as research and development activities.The grant covers the development costs of their PLX cells from March 2008 to February 2009. Furthermore, Pluristem plans to submit an application for a new grant to the OCS in March 2009 to cover the Phase I trial of PLX-PAD and pre-clinical studies of PLX-IBD, targeting Inflammatory Bowel Disease (IBD).

HCT/P establishments must complete annual registration by end of this month. Establishments that manufacture human cells, tissues, and cellular- and tissue-based products have until Dec. 31 to complete their annual registration with the Food and Drug Administration. Instructions for listing HCT/Ps have been revised this year, as have policies and procedures for submitting the form. FDA is encouraging facilities to submit the form thr obtained subject to court approval.ough electronic registration. Review the revised instructions or submit form electronically.

Interesting perspective on stem cells in biotech in BIO's year-end summary of the most important trends and stories of 2008 and looking forward to 2009.

In the spirit of passing along interesting resources, here are a couple I came across this week:

• How Stem Cell Research is Transforming Health Care. A panel discussion from the 2008 World Stem Cell Summit with panelists: Alan Trounson (California Institute for Regenerative Medicine), Lawrence S.B. Goldstein (University of California-San Diego), and John Wagner (University of Minnesota). Moderator: Timothy Kamp
• Steven Badylak @ Pop!Tech 2008. Last year regenerative medicine expert Dr. Badylak made news in the medical world when two of his patients re-grew severed fingertips in just six weeks. He spoke at this year's Pop!tech on how he and his colleagues are applying this breakthrough solution to help Iraqi war veterans re-grow tissue and body parts lost in battle.

Finally, it always disturbs me when I miss important news in the industry because it tells me there are holes in my systems. It also troubles me when I discover cell therapy companies that I here-to-fore did not know existed. Both happened to me this week. Nevertheless, better late to discovery than not at all.

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.

So for what its worth...that's the cell therapy industry I saw this week.

Commercially Available Cell Therapies?

The week of December 2, 2008 I posed the following one-question survey:

Survey
1. How many unique cell therapy* products** do you believe are currently commercially available*** in the world?

* "cell therapy" is defined as any cell-based product involving live cells 'produced' ex vivo and used as part of the therapeutic (not just to create the product) including cell-mediated gene therapies.

** "products" is meant to exclude "mere" stem cell transplantation for any and all indications thus excluding the uses of SCT in regulated markets as well as unregulated SCT services - a "unique product" is one which is distinguishable in a material, technical way from another product (e.g., not just the same product marketed under a different name in different countries).

*** "commercially available" is meant to include any "product" a consumer can purchase whether or not it is part of a clinical trial (given that in some countries these are not mutually exclusive).

I distributed the survey to members of the following groups:

• those who follow me on Twitter (currently a group 66 individuals sufficiently interested in cell therapy to follow my postings);
• my connections on LinkedIn (a group of 203 professionals in or interested in the cell therapy sector);
  
• the 110+ or so members of the LinkedIn Cell Therapy Industry Group;
• readers of this Blog; and
  
• the roughly 55 members of ISCT's cell therapy commercialization committee.

There was no control on multiple responses and no restriction on participation. Participants were forced to choose only one answer among responses ranging from 1-10 to 71-80 in increments of 10 (e.g., 1-10, 11-20, etc).

Data, Assumptions, & Observations
There have been 8 responses to-date. This is a small n but I can't justify spamming my audience any more than I have so we'll have to work with this for now.

If we assume that only members of the groups listed above participated in the survey, then it is reasonable to characterize the participants, at the very least, as informed participants who know more about the cell therapy industry than the average person. I will also assume that participants only voted once.

25% (2 responders) believe there are 10 or fewer cell therapy products commercially available per my definitions. Another 25% responded 11-20. One person thought there were 30-something and another 40-something. A final 25% thought there were 50-some cell therapy products (as I defined them) currently commercially available worldwide.

Once again the quick and easy conclusion is that there is a significant lack of clarity around the current size or maturity of the cell therapy industry even amongst those in or following it closely and who consequently are - at the very least - a lot more informed about it than most.

Analysis
This is admittedly not an easy question to answer because so much hinges on the definition of "cell therapies", whether or not to include the various types of stem cell transplantation products and/or services, and what constitutes a "unique" product (e.g., whether one autologous chondrocyte transplant product for cartilage repair is truly distinguishable from another and how one would define such distinctions).

Let's look at my data. I am currently tracking 700+ companies which I define as stakeholders in the cell therapy sector. This includes ~250 therapeutic companies [i] with ~340 cell-based therapeutic products in the market or in some stage of clinical or pre-clinical development [ii].

Approximately 67 of these 'products' are commercially available in at least one country. There are a number of observations worth noting about these 'products'.

1. Not all of these 'products' have been 'approved' in 'regulated markets'. Some are simple stem cell transplants such as we see in the kind of unregulated clinics discussed in the recent issue of Cell Stem Cell (see the ISSCR Commentary article and a Correspondence article assessing the online portrayal of commercial stem cell transplantation retail ventures providing treatments in unregulated markets). Approximately 17 of the 67 are these unregulated stem cell transplantation “products” where companies are transplanting stem cells in clinics outside the US for a wide variety of diseases with little oversight or published data. I've assumed each such "clinic" has only one product (although that's almost impossible to discern in most instances) and I am certain there are more than 17 such clinics but accurately tracking them is not really one of my goals here.
   
2. Roughly 14 of the 67 are very similar skin (e.g., wound repair/regeneration) products available in various countries;
3. Approximately 10 of the 67 are very similar cartilage repair products available in various countries – many of which are autologous chondrocyte transplant (ACT) products; and
   
4. In some instances, there are multiple inclusions of the same product commercially available through different companies in different countries sometimes under different brand names.

By way of external reference, in his recent publication in Tissue Engineering, M. Lysaght cites 47 companies with at least one commercial product and Proteus Venture Partners often refers to “over 25 FDA-approved cell therapies”.

My analysis of the data leads me to conclude that there are currently ~50 cell therapy products commercially available worldwide. Approximately 26 of these are uniquely distinguishable product types. Roughly 20% (depending on your interpretations) are cell therapies available in the United States. These include extracorporeal photopheresis (ECP) therapy performed using the UVAR XTS, Fusionary, Osteocel\Trinity, Epicel, Carticel, OrCel, Prokera, AmnioGraft, Dermagraft, and others.

Summary
50% of the respondents to my admittedly-small survey believe there are less than 20 unique cell therapy products commercially available worldwide. None selected the 20-some answer (the correct answer according to my data and analysis). From the highly-informed group of respondents, answers ranged from 1-60 products with a full 50% of respondents split evenly between the extreme opposite ends of the spectrum (1-10 vs 51-60).

Conclusion
Regardless of whether my numbers are right, the lack of consensus among those in the sector regarding the size and maturity of the cell therapy industry - or at the very least how one defines it - is clear. For those of us in the industry...it's up to us to fix this. More on that in an upcoming post...

---

[i] Estimates range from ~225 to ~300 therapeutic companies among what I define as ~700 stakeholder companies in the cell therapy industry. Sources: author’s database; Cell Therapy Pages (Connexon Communications); Proteus Venture Partners; Bionest Partners. Cell therapies and tissue engineering. February 2007; Burger SR. 2004. Cell and Gene Therapy - Challenges and Strategies for an Emerging Industry. Cell and Gene Therapy 5:9-14.

[ii] “Pre-clinical development” is defined to product in development prior to initiation of a phase I trial but not including products in the early research phase.

Should I Stay or Should I Go? What's a Good Founder to Do?

Recently I'm come across some valuable articles speaking to the issue of Founder CEO's. We've got a lot of these in cell therapy. It's not an easy decision to stay or leave and the timing is critical. I pass these articles along without any commentary but for the benefit of the industry.

"Company founders: voices of experience". Interviews with nine leading scientists who founded startup companies reveal some common themes and lessons (Published online: 22 March 2004, doi:10.1038/bioent796)

"Moving on". As a company grows, the founding scientist sometimes discovers (and investors often hint) that it’s time to leave the CEO spot and hand it to someone with more business experience. To ease the possible shock of the process, consider this transition from day one. (nature biotechnology volume 26 number 12 december 2008)

"Rich Versus King: The Entrepreneur's Dilemna". (Academy 2006 Best Paper Proceedings). See here for a blog-post about the core concept and for a fuller article in Harvard Business Review (February 2008) see "The Founder’s Dilemma". Most entrepreneurs want to make a lot of money and to run the show. New research shows that it’s tough to do both. If you don’t figure out which matters more to you, you could end up being neither rich nor king. An interesting post-publication discussion can also be found on Wasserman's blog.

Cell Therapy HiLites 2008-12-05

While the cell therapy sector certainly has more than its fair share of companies spreading their peanut butter thinly to survive their burn rate until their next financing closes, another week of funding news and milestones means its not all bad news out there for the cell therapy industry.

Pluristem Therapeutics Inc. (NasdaqCM:PSTI) announced $750,000 of new investment funds - well actually $600,000 from a restricted share purchase and an additional $150,00 from management and BOD members by way of reduced compensation. But the investor has the option, within 10 business days following the initiation of the Company's first human clinical trial, to put in another $600,000.

Osiris completed enrollment in its first Phase III stem cell trial - this one studying Prochymal for steroid refractory acute GvHD - encompassing 244 patients at 74 centers in 8 different countries (N. America & Europe). The last patient is expected to complete the trial in May 2009. MSCs have been reported as an effective agent in the treatment of GvHD by a number of medical centers. In a recent Lancet publication, Le Blanc et al. reported a 55% complete response rate when using MSCs in the treatment of steroid-resistant GvHD. Many people are watching with keen interest to see how the big questions around Osiris' BLA/MAA submissions/approval and then (hopefully) commercial issues like IP, reimbursement and product revenue models will be addressed as Osiris gets ever-closer to market.

Osiris also received approval from Health Canada to expand access to Prochymal for pediatric patients in Canada with GvHD following a similar ruling earlier this year by the FDA. Under the expanded access program, children 2 months to 17 years in age inclusive with Grades B-D acute GvHD not responsive to steroids are eligible for treatment.

Biocompatibles' CellMed treated their first stroke patient in a phase I/II trial with gene-modified, adult, allogeneic, alginate-encapsulated, MSCs dipped into the brain for 14 days (and then removed). The trial is described as the first "authorized" trial using stem cells for stroke.

In this issue of Cell Stem Cell, an ISSCR Commentary article outlines their proposed Guidelines for the Clinical Translation of Stem Cells, available in full online at the ISSCR website. The recommendations include an insistence on expert evaluation and independent oversight, a thorough informed consent process, and transparency in reporting of clinical trial results. This is aimed at all those stem cell transplant clinics selling direct to consumers with little - if any - regulatory oversight, formal clinical trials, or peer-reviewed publications.

Complementing the release of the Guidelines, in a Correspondence article, stem cell law and policy professor Tim Caulfield and colleagues published an assessment of the online portrayal of commercial stem cell transplantation retail ventures providing offshore treatments. Conclusion? They reveal most such clinics exaggerate claims and omit risks.

Organogenesis announced the receipt of two awards honoring the company's development, manufacturing and economic impact. It's been a long and twisty road for the company reinventing itself from Chapter 11 (filed in 2002) but it's certainly now the real deal and a somewhat unheralded beacon for regenmed.

On the not-so-bright side, Cell Genesys, Inc. (Nasdaq:CEGE) and Takeda Pharmaceutical Company Limited (TSE:4502) announced the termination of their collaboration agreement for the development and commercialization of GVAX Immunotherapy for prostate cancer. Takeda will return all commercial rights to GVAX immunotherapy for prostate cancer to Cell Genesys and make certain wind-down payments to Cell Genesys in connection with the phasing out of the remaining clinical development activities.

In keeping with their unique approach to life ACT has formed another ACT. Worcester biotech Advanced Cell Technology Inc. and Korean biotech CHA Biotech Co. Ltd. have formed a new stem cell technology development company called Allied Cell Technology, to be based - wherelse? - in Worcester. The international joint venture will use ACT’s hemangioblast cell technology to develop human blood cells. Allied Cell Technology will be majority owned by CHA, with ACT (OTC: ACTC) licensing its technology for a $500,000 license fee from CHA. Leading the new company in Worcester will be Young Chung, as well as Shi-Jiang Lu and the ACT hemangioblast team. Robert Lanza of ACT will serve as the chief scientific advisor of Allied Cell Technology.

Katarina LeBlanc of Karolinska Institute has been awarded a $1.2 million prize for her work in "immunological characteristics of mesenchymal cells and their use in mesencymal stem cell therapy". The prize, funded by the Tobias Foundation, will be awarded December 17.

Another wannabe cell therapy CMO takes the exit stage right - I think? WuXi-Apptec intends to close its US biologics manufacture operations to focus on testing. Chalk this up to another of several over the past handful of years who have entered - and shortly thereafter exited - the cell therapy CMO business. It's not an easy game and the true players are in it for the long-term. While they announced Wuxi-Apptec will no longer be doing "biologics manufacturing" in the US they said they are now going to focus on "cell therapy". There seems to be some confusion about what exactly that means. I guess we'll stay tuned.

Finally found a half-decent and relatively objective analysis of the recent European Patent Organization (EPO) ruling on the WARF patents sans spin.

On the gene therapy front, Ceregene reported clinical data from a double-blind, controlled Phase 2 trial of CERE-120 in 58 patients with advanced Parkinson’s disease. Regrettably the trial did not demonstrate an appreciable difference between patients treated with CERE-120 versus those in the control group. Continuing the theme, Introgen Therapeutics, Inc. (NASDAQ:INGN) announced that as part of its ongoing restructuring, the company has elected to file Chapter 11 petitions in the U.S. Bankruptcy Court. The EMEA has accepted, from Introgen's wholly-owned subsidiary in Ireland, Gendux Molecular Limited, a Marketing Authorization Application (MAA) for Introgen's ADVEXIN to treat recurrent, refractory head and neck cancer. However in September 2008, the FDA notified Introgen that the BLA was not sufficiently complete and would not be filed at that time. Demonstrating once again that success and failure are a hair's breadth apart.

HemoGenix announced the implementation of biorisk-free, green-source growth factors and cytokines for use in all HALO® Assay Kits and HALO® Contract Research Services

CBER has been busy these past few months. FDA released another new Guidance this week. This one: Guidance for Industry: Cooperative Manufacturing Arrangements for Licensed Biologics.

NovaRx Corporation appointed former CSO of Invitrogen - remember them? - Norrie J.W. Russell, Ph.D as President and COO this week. His pedigree should be invaluable as NovaRx manages the late-stage development of it lead product candidate, Lucanix(R) - a whole cell-based therapeutic vaccine comprised of four allogeneic cell lines, currenly in Phase III clinical trial for the treatment of progressive non-small cell lung cancer. Once fully open, the trial is expected to run in 90 centers in the US, Canada, Serbia, Hungary, UK, Netherlands, Germany, Poland, Italy, and India.

And finally, on the mere speculation front, yet another analyst has identified Genzyme as a ripe acquisition target by one of those cash-rich, pipeline-poor pharma's on a shopping spree.

That's the cell therapy industry as I saw it this week...