Cell Therapy Industry HiLites 2009-02-20

Before we get started, here's some good advice:

• renew your membership or join ISCT (www.celltherapy.org)
• if you're on LinkedIn, join the Cell Therapy Industry Group
• register to go this year's ISCT CellTherapy 2009 conference in San Diego
• get on Twitter, and follow my stream (@celltherapy) for timely news and random thoughts
• tell someone you love them.
  
  
  
  

Ok. Another week, another conference, another controversy, another clinical hold...

This was the week of RRY Publications' 4th Annual Stem Cell Summit, organized by investor and analyst Robin Young. Once again, Monya Baker, of Nature's stem cell blog "The Niche" does an outstanding job of summarizing the conference content and tenor in a post called "Investors ♥ stem cells". My only humble comment is that it might have been more aptly named "Entrepeneurs ♥ stem cells" because I don't think the plethora of companies and technologies represented at the conference was due to a flood of investment but rather the irrational (thank God!) enthusiasm of biotech entrepreneurs that keep sectors like this afloat whilst risk-averse investors await the obvious to float to the surface.

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The big pile to hit the fan this week was the PLoS Medicine article published online February 17 describing a patient who developed “brain tumors” (glioneuronal neoplasms) after undergoing repeated transplants of “fetal neural stem cells” in Russia starting in 2001. Fellow bloggers Monya Baker @ the Niche (click here >>) and Alexey at Hematopoiesis.info (click here>>) both provide useful summaries and commentary .

Naturally it is a concerning report for the industry and the regulators. People jumped all over it touting their various perspectives and generating a veritable miasma of opinion. Indeed, so much so that Stem Cells, Inc (NASDAQ: STEM) was forced to publish a commentary on the report in an attempt to distinguish their product from what was apparently injected into the boy in Russia. STEM's commentary is worth the read.

What I will say here - apropos to my ongoing discussion about stem cell transplant clinics around the world enticing people to pay for a shot of stem cells because 'why not? these products are safe' - is that there are stem cells and then there are stem cells and then there are stem cell products. Products are well studied, well understood, well defined, well characterized, well controled, and well tested.

Ex-FDA, regulatory consultant Dr. Darin Weber (blogging at RegenmedGuru.com) has a great post on this whole issue that is well worth the read. He sums up his commentary by saying:

The bottom line is that if you wish to test stem cells in humans in the U.S., the FDA is going to require robust evidence of efficacy and safety in relevant preclinical animal models, regardless of the source.

Now the FDA has an clear example it can point to, for better or for worse, to justify the extensive preclinical studies it requires. The good news is that many developers of stem cell derived therapies, including Geron, have in fact been able to generate the preclinical efficacy and safety data needed to enter human clinical studies.

So why is the FDA "holding back" stem cell treatments that are available in other countries? Why should people think very carefully about their decision to go to a clinic offering stem cell injections for sale? Why is 'industry' critical of what some of these clinics are doing? Why should we be concerned about whether these 'treatments' are as safe as advertised? We now have an example of why.

This is no justification for being over-reactionary about the potential for cell therapy. This is not even a good reason to paint all unregulated stem cell treatments with the same brush. It is a reason to be ever-vigilant in ensuring we are doing our utmost to produce effective AND safe therapies. It is also reason support the dialogue ISSCR is attempting to stimulate to help people discriminate between those clinics following best practices and those which are not.

In the meantime, people are getting shot up with sheep stem cells in Mexico (check it out) ...

FINANCIAL

No news is not really good news here.

CLINICAL

Neuralstem, Inc. (AMEX: CUR) announced today its spinal cord stem cell trial to treat ALS has been put on clinical hold. This seems to be pretty par for the course at this stage. The question will be how long it takes to address the issues. Geron was able to get through their hold in under 9 months; ReNeuron submitted its IND to FDA in December 2006 and has yet to get it through despite being approved to proceed in the UK last month. See Monya Baker's commentary on Neuralstem's hold on Nature's stem cell blog, the Niche - click here >>.

Neuralstem was more forthcoming with details about their hold than Geron was when in the same position months ago. The FDA has reportedly provided the Company with specific comments, questions and recommendations for modifications to its protocol including requests for additional information regarding their product manufacturing process and pre-clinical studies, as well as their clinical delivery injection device and technique. The Company believes that it can "provide this information in an expeditious manner."

Apparently the Agency has also requested various modifications to the protocol and eligibility criteria for patients in the trial, as well as slight changes to the timing of the surgeries. Perhaps more interesting was the comments by President & CEO, Richard Garr that the "Agency had extensive 'non hold' comments, requests for information, and recommendations" which he characterized as issues which will need to be "addressed for final product manufacturing and testing". By that, I'm assuming he means the FDA raised several issues which wouldn't hold up phase I testing but certainly would need to be addressed in future stages.

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HepaLife Technologies, Inc. (OTCBB: HPLF) (FWB: HL1) (WKN: 500625) announced plans for a phase III clinical trial of its HepaMate™ Bioartificial Liver System. The HepaMate™ technology has previously been tested in clinical Phase I and pivotal Phase II/III studies involving more than 200 patients. However the last phase II/III study failed to achieve its primary endpoint. In October 2008, HepaLife announced completion of its acquisition of a liver support technology previously known as HepatAssist from Arbios Systems. It's not clear how, if at all, this is playing into HepaLife's current strategy.

As an extracorporeal cell-based bioartificial liver system, HepaMate™ is designed to combine blood detoxification with liver cell therapy to provide whole liver function in patients with the most severe forms of liver failure. HepaMate™ is comprised of a blood plasma separation cartridge, a hollow-fiber bioreactor filled with proprietary porcine liver cells, a charcoal column, an oxygenator, circuit tubing and a plasma reservoir. These components are assembled into a patented blood/plasma circulation system, which is placed on the HepaDrive™ perfusion platform.

A patented liver cell cryopreservation process provides for safe and easy storing and distribution of the liver cells which detoxify existing toxins, produce albumin and other liver-specific proteins when, during therapy, the patient’s plasma is separated from whole blood, exposed to the HepaMate™ bioartificial liver and returned to the patient.

The company claims only 90 minutes are required to assemble the system, prime the blood and plasma circuits and to process the liver cells due to the logistical advantages of its proprietary cryopreserved pig hepatocyte technology over the use of fresh cells from cell lines or liver tissue.
Thawing, loading and washing of the cryopreserved cells is reported performed at the patient’s bedside using a what the company describes as a proprietary, "FDA-approved" technique.

Apparently a retrospective statistical analysis of the previous pivotal Phase II/III clinical trial data, adjusted for the impact of liver transplantation on patient survival, revealed a statistically significant survival advantage for patients with fulminant and subfulminant hepatic failure when treated with HepaMate™ compared to controls receiving standard medical care alone. The company blames the previous trial's failure on the inclusion of a subset of 24 patients who had undergone a prior, failed liver transplant. It was these patients, the company postulates, that led the the phase II/III trial failing to achieve its primary 30-day survival endpoint in the overall study population. Based on the retrospective statistical analysis of the clinical trial data, HepaLife expects a new Phase III clinical trial without the inclusion of failed liver transplant patients to be successful.

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It's now clear why J&J is closing its Sydney, Australia operation which was investigating OZ1 as its lead product against HIV. Earlier this week a report came out entitled "AIDS: 'Major advance' seen in revolutionary gene therapy'. It was an interesting spin. What was learned from the study in question was a 'major advance' only in the minds of scientists who can chalk this study up to 'lessons learned' from less than positive results. We're no closer to a therapy based on this product.

The report indicated that the world's largest experiment using gene therapy to combat the AIDS virus yielded "a major advance," in demonstrating that the technique is valid, beneficial and safe. "It shows the potential of the gene therapy approach for the treatment of HIV and represents a major advance in the field... [it] can be developed as a conventional therapeutic product," the report stated. Yet later the report admited that while the treatment is safe efficacy was modest. Finally, the report states that in an interview, the principal investigator, Mitsuyasu, said they would not be proceeding past this Phase II trial to the final, third phase of the process. Instead, the team would learn from its experience, modify the technique and start again with tests on a smaller group of volunteers.

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This week NeuroGeneration put out a press release that boldly states it published long-term results of a successful phase I trial using autologous neural stem cells to treat Parkinson's disease. Despite the over-reaching headline, this is not the data from a completed phase I trial but rather the results from the trials' first (and only?) patient. Really more of a case report.

The paper was published in the February issue of the Bentham Open Stem Cell Journal. It outlines the long term results of the treatment of a patient for the treatment of Parkinson’s disease using autologous neural stem cells. According to lead author and NeuroGeneraton owner/founder, Michel F. Levesque, MD, FRCS(C), FACS, "We have documented the first successful adult neural stem cell transplantation to reverse the effects of Parkinson’s disease and demonstrated the long term safety and therapeutic effects of this approach."

The paper described a process by which tissue is taken from the patient's cerebral cortex and expanded for 6 months (yes, 6 month!) before injection. The paper's conclusions:

• Neural stem cells can be isolated from the human adult cerebral cortex, expanded in vitro using epigenetic factors, induced to differentiate into dopaminergic, GABAergic and other types of mature neurons, and selectively delivered back to striatal targets without immunosuppressant.
• Because of their biocompatibility, safety and potential integration into the host striatum, autologous neural stem cell-derived differentiatedneurons represent an alternative to current cell therapy aimed at the restoration of the nigro-striatal circuitry inParkinson’s disease.
  

COMMERCIAL

MaxCyte, Inc announced the introduction of its GT Flow Transfection System at the 4th Annual Stem Cell Summit held in New York, NY this week. The MaxCyte GT Flow Transfection System is marketed as a a validated, scalable technology for customizing the biological activity of cells for therapeutic use. The system, the subject of a US FDA Master File, is designed to enable rapid and efficient transfection of primary cell or cell line with reported >90% cell viability following loading with a broad range of molecules (proteins, drugs, plasmids, mRNA, miRNA, and siRNA) or combinations thereof, at volumes up to tens of billion cells.

What's not clear to me is how this system is different from the clinical scale, non-viral cell loading systems MaxCyte has been selling now for some time and a quick spin through their website has not helped shed any light on that question. Indeed there is nothing about a product launch on their website so this product "introduction" might just be clever spin around a talk about a product that has been on the market for some time. I'll try to find out...

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MedCell Bioscience Ltd (merged last year with NovaTherapy) announced they won the Hong Kong Grand Award for their NovaPod - a compact, manual feed, disposable, batch culture bioreactor that allows researchers and scientists working on stem cells to culture cells in three dimensions. The Hong Kong Grand Award for Industries, Machinery and Machine Tools was presented on 21 January 2009 at the Hong Kong convention and exhibition centre.

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Ok this isn't cell therapy but it's about the so-sexy, so-'now' iPS cells so I couldn't resist. The Japanese unit of German chemical giant Bayer A.G., Bayer Yakuhin Ltd, has announced it is selling a set of patents on producing iPS cells to a U.S. venture firm. The three patents to be sold to iZumi Bio Inc include Bayer Yakuhin’s main method of producing iPS, or induced pluripotent stem cells, which have the potential to grow into any type of human body tissue. Bayer Yakuhin filed for Japanese and international patents on the method in June 2007. The two other international patents are supportive ones for the mainstay one. Bayer Yakuhin’s move has been closely watched since it made patent applications months ahead of Kyoto University.

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StemCellDigest.net did a nice job this week of detailing the historic and rather complicated but much closer licensing relationship than I realized existed between Advanced Cell Technology Inc. (OCTBB: ACTC) , Biotime, Inc, (AMEX: BTX) and International Stem Cell Corp (OTCBB: ISCO). To read more, click here>> .

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ProtoKinetix, Inc (OTCBB: PTKX) issues a press release this week that their synthetic anti-aging glycopeptide, AAGP, is "Critical for Stem Cell Therapy" saying that tests of the compound in conjunction with stem cell preservation studies at all temperatures has shown an "impressive increase in survivability and viability". Reportedly, these results have been consistent regardless of the source of the stem cells. As an example, AAGP(TM) has been independently tested as a protective agent in the cryopreservation and subsequent thawing of umbilical cord blood in low concentrations of AAGP(TM) (4mg/ml). The resultant analysis reportedly revealed a more than double average increase over the control group (cells not protected with AAGP(TM)) in the yield, following thawing. Sounds impressive enough but they provide no links to publications and despite the headline that AAGP is 'critical' for stem cell therapy, I've not seen or heard them at any stem cell conference nor have I seen any of the data published in journals. Curious...

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Stem Cell Therapy International, Inc. (OTC BB:SCII.OB) - another of these companies marketing stem cell transplant treatments in clinics located in countries where they are allowed to do so - has filed its quarterly report. It is a long and twisted tale of corporate re-orgs, reverse mergers, subsidiaries, debt, financings, payments in salaries and consultanting fees, zero revenues, and a pending deal with the Korean company, Histostem Co., Ltd., that was first announced early last year and has yet to close because of some litigation that won't go away. As best I can tell from a quick scan of the SEC filings they did not treat a single patient in 2008 - perhaps that's the good news.

RESOURCES & EVENTS

MIT Enterprise Forum of Cambridge announced an upoming session (March 3rd) on the Future of Biotech with a panel of experts who will discuss Challenges and Opportunities in Stem Cell Therapy and Regenerative Medicine.

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The FDA has posted what could be a very useful presentation if the right (wrong?) circumstances: Writing An Effective 483 Response.

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Curt I. Civin and E. Albert Reece put out a piece this week in the Baltimore Sun entitled "The Stem Cell Opportunity" outlining some of their thoughts on the state, need, and potential for the sector.

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A summary of the most recent ISCT Cellular Therapy Liaison Meeting with the FDA has been posted on the AABB Web site, along with corresponding speaker presentations. Agenda items for the meeting, which was held in October 2008 at the AABB National Office, included "Adoptive T-Cell Therapy for Melanoma: Production Steps and Associated Costs," "Autologous Expanded T-Cell Therapy in Post-Transplant Setting," and "HESC-Derived Cell Therapies: Safety in Translation." View summary


Sign-off...

Well, that's a wrap to an a wee bit of an odd but not entirely bad week in the cell therapy industry. For those of you with any doubts, remember you heard it here first: cell therapy means business.