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Saturday, February 28, 2009

Cell Therapy Industry HiLites 2009-02-27

I'm pretty excited by how well the blog is being received. This is a small, niche segment of the biotech sector and I only cover the commercial aspects of the segment so the numbers are small but - as you can see from the graph on the right - the number of people checking out the blog is certainly growing exponentially. This month we passed 1200 visit and 2200 views. Thanks for spreading the word...

Apparently this is the week for which we've been waiting for 40 years. Peter Winter reports to the
Burrill Report that the biotechnology industry is now profitable.

The 360 publicly listed companies they track generated $9.4B in revenue in 2008 with a net income of $3B. 67 of these companies companies were profitable with the remainder generating red ink of $6B. The bulk of the income was, of course, generated by the top 3: Genentech, Amgen, Gilead - reporting a combined net income of $8B. 200 of the companies are in fiscal trouble with many having only 6-12 months of cash left. Peter speculates one-third of the companies being tracked today may not exist as-is one year from now - perhaps to the benefit of a stronger sector.


The VC panel at the Stem Cell Congress (CHI's Molecular Medicine Tri-Conference) in San Francisco this week was asked whether - if they were given it - they would take $500M to invest over a 5-year term and get out over the next 5 years with the 'usual' VC expectations of return. Only one string: the investments would have to be restricted to regenerative medicine companies (defined widely to include therapeutics, tools, devices, platforms, reagents, etc). Tellingly, they all answered 'no' or that they would take only part of the money. They were all VCs very familiar with the space and even personal cheerleaders for it but they all felt it was too early to find enough companies they could invest that much money in with confidence of giving the requisite returns. I'll be exploring this more in blogs to come.

With that, the only official financial news is not an investment but a loan. Wisconsin Governor Jim Doyle announced that Stratatech Corporation in Madison will receive a $500,000 loan from the Department of Commerce.

Unofficially, executives from SanBio, Inc confirmed for me this week that they have received a small (hopefully precursor) investment from Fujifilm Life Science. Amounts were not disclosed. This reportedly modest financing is intended to get SanBio through its IND approval. The company is actively fundraising.


Angioblast Systems Inc announced the successful achievement of the key safety milestone in the first low-dose cohort of patients treated with Revascor(tm), the proprietary allogeneic, or "off-the-shelf", universal adult stem cell product for congestive heart failure. Safety data from all 20 congestive heart failure patients enrolled in the multi-centre Phase 2 clinical trial were reviewed by the trial's Data Safety and Monitoring Board (DMSB). No cell-related adverse events occurred in any patient during the 30-day follow-up period and the review was positive. As a result, the DSMB has allowed the company to move forward with recruiting the second 20-patient cohort of patients with congestive heart failure. This group will receive a higher dose of cells.

The placebo-controlled trial of Angioblast's Revascor(tm) cell therapy will randomise up to 60 patients suffering from congestive heart failure to three 20-patient cohorts receiving either a progressively increasing dose of the company's allogeneic adult stem cells or standard of care. The cells are implanted into the damaged heart muscle using the NOGA MyoStar catheter technology system provided through a collaborative agreement with Johnson & Johnson companies, Biologics Delivery Systems and Cordis Cardiology. The outcomes in each patient group following injection of progressively increasing doses of cells will be compared against standard-of-care in terms of both safety and effectiveness at halting or reversing congestive heart failure. The company will provide interim efficacy results for each dose cohort as they become available.

Cytori Therapeutics, Inc. (NASDAQ: CYTX) released a press release entitled "Adipose-Derived Stem and Regenerative Cells Prevent Mortality and Reduce Kidney Damage in Preclinical Study"preclinical results". The opening line of the reiterated that the data reported were "preclinical results". The release also clearly stated the "study was performed using a manual extraction technique" though it did speculate that the "potential application could be made more efficient and cost effective with the use of Cytori's Celution(R) System to isolate clinical grade ADRCs in real time"., however, was critical of the release in a blog entitled "Now You See It, Now You Don't" - The Latest Cytori Press Release" calling the company one of the most "flamboyant" in the sector and its communications style and treatment of the facts as taking "liberties with unwritten research release protocol that is a bit beyond the pale". They said: "Quickly read, the release seems to suggest that this was a clinical study". Now I understand the comment that Cytori certainly seems aggressive in its communications style but one would have to read this latest press release awfully 'quickly' to believe it was data from a clinical study despite the references to animals (mice?) as 'subjects' - admittedly not a standard practice.

Intercytex Group Plc (AIM: ICX) has products on the market and other products in its phase II pipeline but it has recently trimmed a significant amount of staff to cut back on costs and now in a recent stock exchange statement the company states it is going to abandon its only phase III trial - that of Cyzact® for venous leg ulcers. Indeed "no further work on Cyzact® is planned in any indication" and "in the light of this disappointing result the board has determined to review all strategic options for the company" including "a possible merger or sale of the business".

For the second time this month, we've had a press release with the general theme of: 'we're closing up shop now...hope we contributed to the science'. At the ASCO meeting this week Cell Genesys, Inc. (NASDAQ:CEGE) announced results from further analyses of their prematurely closed VITAL-1 and VITAL-2 clinical trials studying GVAX immunotherapy for prostate cancer. Both trials were shut down earlier this year and the company is being cratered.

VITAL-1 was a Phase 3 clinical trial designed to compare GVAX cancer immunotherapy as a monotherapy to Taxotere chemotherapy plus prednisone in castrate-resistant prostate cancer (CRPC) patients with metastatic disease who were asymptomatic with respect to cancer-related pain. The primary endpoint of the trial was an improvement in survival. In 2007, the VITAL-1 trial completed enrollment with 626 patients at 131 sites in North America and the European Union. In January 2008, Cell Genesys announced that the Independent Data Monitoring Committee (IDMC) had completed a pre-planned interim efficacy analysis for VITAL-1 and recommended that the study continue, providing no further information to the Company other than the recommendation to continue the trial. On August 27, 2008, the Company announced that it had requested the IDMC to conduct a previously unplanned futility analysis of VITAL-1. VITAL-1 was terminated in October 2008 based on the results of a futility analysis conducted at the Company’s request by the study's IDMC which indicated that the trial had less than a 30 percent chance of meeting its predefined primary endpoint of an improvement in overall survival. Based on the results of that analysis, the Company terminated the VITAL-1 trial in October 2008.

The final Kaplan-Meier survival curves for the two treatment arms suggest a late favorable effect of GVAX immunotherapy on patient survival compared to chemotherapy, with the curve for GVAX patients crossing above the chemotherapy curve at approximately the same time median survival was reached in both treatment arms (21 months). Additionally, the data suggest that patients with Halabi predicted survival (HPS) greater than or equal to 18 months may have a more favorable response to the immunotherapy. Treatment with GVAX immunotherapy was generally well-tolerated and had a very favorable side-effect profile compared to Taxotere chemotherapy particularly with respect to a lower frequency of grade 3 or higher toxicity of nine percent versus 43 percent.

VITAL-2 was a Phase 3 trial designed to compare GVAX immunotherapy in combination with Taxotere to Taxotere plus prednisone in CRPC patients with metastatic disease who were symptomatic with respect to cancer-related pain. The primary endpoint of the trial was also improvement in survival. VITAL-2 was initiated in June 2005 and had enrolled 408 patients at 115 clinical trial sites located in North America and the European Union prior to study termination. On August 27, 2008, the Company announced its decision to terminate enrollment and treatment with GVAX immunotherapy in VITAL-2 as recommended by its IDMC which, in a routine safety review meeting held at that time to review both VITAL-1 and VITAL-2, observed an imbalance in deaths between the two treatment arms of the VITAL-2 study.

Updated analyses show no significant toxicities in the GVAX plus Taxotere arm that could explain the imbalance in deaths. Eighty-five percent of deaths were reported as due to prostate cancer in both arms, and there was no trend in the causes of death in the remaining patients. These observations are consistent with the hypothesis that the decision to omit concomitant prednisone in the GVAX immunotherapy treatment arm to avoid the immunosuppressive effects of prednisone may have contributed to an unfavorable outcome compared to the combination of chemotherapy and prednisone. Additionally, it is important to note that further analyses of VITAL-2 have indicated that the imbalance in deaths between the two treatment arms has decreased from 20 deaths as reported at that the time of the IDMC’s initial analysis (August, 2008) to 9 deaths at the time of the final analysis (December, 2008).


Osiris Therapeutics, Inc. (NASDAQ:OSIR) announced its results for the fourth quarter and year ended December 31, 2008. It's list of recent and 2008 highlights is admittedly impressive:
* Formed major strategic alliance with Genzyme Corporation worth up to $1.4 billion for the development and commercialization of Prochymal and Chondrogen in countries outside the United States and Canada.
* Sold the Osteocel business to NuVasive, Inc. in a transaction worth up to $85 million in upfront and milestone payments.
* Awarded Department of Defense contract fully valued at $224.7 million to develop and stockpile Prochymal for acute radiation syndrome (ARS).
* Received approval to initiate Prochymal expanded access program in the US for adult and pediatric patients and in Canada for pediatric patients suffering from life-threatening Graft versus Host Disease (GvHD).
* Completed enrollment in first worldwide Phase III stem cell clinical trial for the treatment of steroid-refractory GvHD.
* Reported positive two-year data from Phase I clinical trial evaluating Prochymal in heart attack patients.
* Completed enrollment of Phase II clinical trial evaluating Prochymal in patients with chronic obstructive pulmonary disease (COPD).
* Reached agreement with the FDA regarding the timing and content of the submission of the first marketing application for a stem cell product.
* Reported cash, short-term investments and receivables of $123.5 million at year-end.

Genzyme Corp.'s chief executive Henri Termeer said the company may spend about $600 million this year to acquire products that treat chronic diseases - likely personalized drugs, highly specialized medicines already tested in humans. He prefers, he says, the idea of buying products rather than entire companies.

Despite being on the verge of closing a multi-million dollar financing, expecting to launch a commercial product next month, and reporting promising findings on the her company's experimental hair regrowth treatment last week at the 4th Annual Stem Cell Summit in New York, Histogen, Inc founder and CEO Gail Naughton has just had to fire all her employees. A patent infringement lawsuit filed last month against Histogen has triggered a funding crisis at the San Diego biomedical startup, which was forced to lay off all 36 of its employees at the end of January. The suit filed by rival SkinMedica of Carlsbad, CA, also prompted a group of angel investors to withdraw their planned $2.4 million investment in Histogen at the end of January. Naughton said the lawsuit was filed to stop the planned March 6 launch of the cosmetic products.

ThermoGenesis, Corp. (NASDAQ:KOOL) announced that the FDA has agreed with its plan to remedy the voluntary recall of certain lots of AXP disposable bagsets that it announced in November. At that time, the Company had indicated that the recall was not the result of any safety issues; the field action was a result of the potential for particulates to be released into the sterile, non-pyrogenic fluid path as a result of a defective component provided by one of the suppliers to the Company. The Company indicated that it was providing customers a blood filter to be used, as necessary, with any bags that had already been processed.

Cordlife Ltd (ASX: CBB) reported its 2008 year end financial results. Cconsolidated revenue and other income for the half-year ended 31 December 2008 increased by 78% to $13,218,000 from $7,439,000 for the half-year ended 31 December 2008. Revenue from cord blood banking services was $11,436,000 for the half-year ended 31 December 2008 as compared to $7,006,000 for the half-year ended 31 December 2007 (an increase of 63%). This substantial growth is due to significant increase in client sign-ups across the Group's existing markets of Singapore and Hong Kong. Several marketing and promotional measures were put in place in the first half of this financial year in our two largest markets. The additional sign ups in Singapore are also due to incentivised schemes from the Singapore government to aid first time parents financially. There was also growth across the Group’s other markets in Australia, as well as Indonesia. India registered its first clients and revenue in the first half of this financial year. Net profit attributable to members for the half-year ended 31 December 2008 was $1,590,000, an increase of 997% over the net profit attributable to members of $145,000 for the half-year ended 31 December 2007.

Cord Blood America, Inc. announced an agreement with Shelter Island Opportunity Fund to restructure its current outstanding debt. With the signing of the agreement, Cord Blood America projects it will become cash flow positive for the first time in its history. The loan originally helped CBAI to acquire a large customer base with the CorCell acquisition. The principals of Shelter Island Opportunity Fund worked with us to restructure our debt, putting us in position to run as a cash flow positive organization. "This is a gesture of true partnering with CBAI, while sharing the stem cell vision to become a globally dominant stem cell storage company", said Matthew Schissler, CBAI Founder and CEO.

BioTime, Inc., (OTCBB:BTIM) announced that its wholly-owned subsidiary Embryome Sciences, Inc. has entered into an agreement with Reproductive Genetics Institute (RGI) of Chicago, Illinois granting Embryome Sciences rights to market new human embryonic stem cell (hES) lines selected by Embryome Sciences from 294 hES lines derived by RGI. Embryome Sciences will initially select 10 RGI hES cell lines, and may add additional cell lines at its option. RGI is a leading fertility center that screens embryos for genetic disorders, such as cystic fibrosis and muscular dystrophy prior to implantation. The RGI hES lines include both normal cells and 88 cell lines identified as carrying a host of inherited genetic disease genes that Embryome Sciences plans to sell as research products to universities and pharmaceutical companies.

NeoStem, Inc. (NYSE Alternext US: NBS) announced it has signed a license agreement to obtain the exclusive worldwide rights to innovative stem cell technology and applications for cosmetic facial and body procedures and skin rejuvenation. This "innovative stem cell skin rejuvenation procedure" is intended to enhance NeoStem's leadership in the anti-aging and regenerative medicine arena - one of their "core pursuits".

Voted one of 2008's Top Ten small companies (<1,000 href="">Tengion, Inc was a Feature Company this month on the T engion is a clinical stage regenerative medicine company focused on developing neo-organs and neo-tissues derived from a patient's own (autologous) cells. The Company's lead product, the Tengion Neo-Bladder™, is currently in Phase II clinical trials in the United States in pediatric patients with spina bifida, and adult patients with spinal cord injuries.

Cell isolation/collection companies join forces - Gahaga Biosciences has been acquired by Hemacell Perfusion.


All the articles are available for free download in a special issue of MAL's Tissue Engineering Part A: Technologies for Enhancing Tissue Engineering: Materials and Environments for Guiding Stem Cell Function. Guest Editors are E. Alsberg and J.A. Rowley.

Two prominent supporters of stem-cell research said they had reintroduced a Senate bill that would allow federal financing for human embryonic stem-cell research, in anticipation of President Obama’s support for the work. The advocates, Senators Tom Harkin, left, Democrat of Iowa, and Arlen Specter, Republican of Pennsylvania, said their measure would allow federal financing for research using stem cells taken from human embryos left over from fertility treatments. “It is the same bill that both houses of Congress approved in 2007, but was vetoed by President Bush,” they said. Mr. Obama has promised to overturn Mr. Bush’s policy strictly limiting the use of federal money for such research.

Proposed legislation which would allow companies to grab a share of the $18 million stem cell fund, is pitting the Maryland's biotechnology companies against academic researchers.

Sign off...

In the long-term, one of the take-homes from this week's conference in San Francisco is continued encouragement by the outside players now actively strategizing about how they will participate in the cell therapy industry. This will (a) inject cross-disciplinary intelligence, experience, and maturity into the industry, (b) allow companies in the sector to leverage expertise from outside the sector that can be used to take companies and technologies to the next level of commercial viability, and (c) represent an increasing number of potential M&A partners.

In the short-term, there was nothing to refute the general sense that this is going to be a long and game-changing year for many companies in the sector.

In the meantime, CellTherapyBlog will bring you the good, the bad, and the ugly from the cell therapy and regenerative medicine industry...

Monday, February 23, 2009

Cell therapy products vs cell therapy products; stem cell clinics vs stem cell clinics

I will find a new favorite topic in due course but for now this drum needs a little more beating. The feedback I've been getting is helping me get to the heart of the matter.

Here on these very ephemeral 'pages', I have suggested that the cell therapy industry is not well informed about how many cell therapy products/treatments are currently commercially available worldwide. Some in the industry argue that many of the products I include are not 'real' cell therapy products/treatments (more on that in a minute...) so they shouldn't really be counted.

I have also been sympathetic to unregulated stem cell clinics around the world and the patients that access them while advocating for and supporting the implementation of more stringent ethics, business practices, and therapeutic regulation.

Both sides of this debate have provided useful feedback and perspectives.

Ardent supporters of unregulated stem cell clinics, accuse me of criticizing their pioneering efforts to treat patients that the medical industry can't or won't treat. They believe I tow the party line on the need for rigorous scientific evidence, regulated clinical trials, peer-reviewed publications and a therapeutics review/approval framework. They accuse this view as archaic and not permissive of allowing patients the right to determine their own treatment pathway particularly when there is no harm in the cell-based products being sold.

On the other hand, some of my peers in the cell therapy industry believe I am doing a disservice to the industry by acknowledging that these unregulated stem cell clinics are part of this sector and are doing a robust business with an increasingly large number of American patients.

I happen to believe that just because a company is operating in an unregulated market does not necessarily mean they are unethical, that it may not be fair to characterize all 'stem cell clinics' in unrelated markets as 'the same', and there may be some of these clinics which are conducting business is ways which should be considered acceptable.

In the spirit of informed and informative discussion, I have 4 comments - not in an attempt to be defensive or argumentative but to keep what I believe to be a valuable discussion flowing.

1. There are those that want to believe they know the products available in the market and if there is any gap between their number and mine it is entirely comprised of unregulated products in unregulated markets.
Wrong. A large percentage of this gap is comprised of regulated products.

According to my data there continues to be a wide gap between the perception of how many cell therapy products are commercially available in markets around the world and how many there actually are.

For example.

At the 2009 Phacilitate Cell & Gene Therapy Forum the very first speaker of the conference inferred (by mistake) that there was only one cell or gene therapy product approved in the world. He meant gene therapy products. Based on that presentation, however, there were delegates at the conference - people who work in the cell therapy industry and should clearly know better - who were tempted to believe there was only one approved cell or gene therapy product in the world. These are people who would know better if they thought about it for a minute. That's an egregious example but watch the interviews of delegates by and you will see most experts in the field believe there is but a handful of approved cell therapy products worldwide.

According to data in a recent TERMIS newsletter, for example, there are 10 cell therapy products in Korea alone that have been approved by the Korean FDA (KFDA) for treatment of various conditions. This is a regulated market and these are regulated products owned and sold by companies. According to my data there are at least another ten approved products between Australia and Germany. Again both regulated markets. That is already more approved products than most people believe are available in the world.

So yes... I certainly have included unregulated products/treatments in previous data.
Nonetheless, but even when I exclude these, the number is larger than most believe.

This is the gap I want to close the most. The more I interact with people now as they react to my data and perspective, I believe I am starting to get a clearer picture about what is behind some of this gap.

2. There may be some who disagree with my definition of 'product' and/or use of the adjective 'approved'.

I have to-date considered it a 'product' whether it is cGMP or cGTP and whether or not it is the subject of an IND/BLA (or equivalent) . I'm certain the FDA CBER shares that view. 'Approval' of a product does not only come by way of BLA/MAA (or equivalent), it also comes from tacit approval in regulated markets where a product falls within a category which is allowed without formal application for review and approval by the regulatory authority.

So, for example, the Xcell-Center clinic in Germany currently provides bone-marrow derived, minimally-manipulated stem cell 'products' under the authority of the German regulatory authorities. They do so on a commercial basis. The products ('treatment' some might prefer) are currently being sold to treat patients with the following (degenerative) diseases: ALS, alzheimer's disease, cardiovascular diseases, cerebral palsy, diabetes mellitus (type 1 & type 2), erectile dysfunction, macular degeneration, multiple sclerosis, osteoarthritis, Parkinson's disease, spinal cord injuries, and stroke.

It's not clear to me whether there is any unique IP around these treatments and the business model here is clearly more of service model than product model but the products/treatment may each be somewhat different and may be administered differently depending on the indication. By at least some people's definition, that is at least 12 different 'products' - all being sold with complete regulatory approval (though not an MAA because of the nature of the products/treatments) - with prices starting at around 12,000 euros depending on the procedures required. Some might argue it's only 1 product but isn't it at least that?

In regulated markets stem cell transplantation is a regulated cell therapy in that there is a regulatory framework within which the service falls and one cannot simply transplant stem cells for any indication one wants (let's say pump them into the brain) even if one simply takes them from the bone marrow, isolates the cells of interest and puts them straight back in.

Stem cell transplantation is commonly perceived to be a medical procedure rather than a product but this does not make it any less a cell therapy. If the cells are more than minimally manipulated they become defined as a cGMP product (in the US). At what point in between does it cross the line and become a 'product'?

Is it whether or not there is IP around the product or process used to make it? Is it whether or not it is characterized primarilyy as a 'service' rather than a 'product'? Certainly some cGMP products will require an extensive clinical service model. It certainly seems to me that at least some cGTP products will be no less cell therapy products than a cGMP product in that they may be the subject of IP and may involve no more of a service element than some cGMP cell therapies.

3. There must be a way to have an informed discussion in which we distinguish between cell therapy products and cell therapy products; stem cell clinics and stem cell clinics.

The Xcell-Center, for instance, operating under complete regulated authority in a regulated market providing treatments for a limited number of conditions and conducting at least some type of long-term follow-up must be considered in a substantially different light than a clinic providing stem cell injections for almost any condition in an unregulated market, without any long-term follow-up, and with no transparency as to their product or process.

I believe the ISSCR and many others share my desire to create the foundation for what will become for patients - in an informed and global medical market - a very important discussion upon which they can discriminate between legit and shoddy clinics and make informed decisions.

4. As for those clinics arguing they should not be not be subjected to standards requiring
rigorous scientific evidence, regulated clinical trials, external audits, and peer-reviewed publications within a therapeutics review/approval framework... please stop. Stop now.

Cell therapy is not inherently safe regardless of what kind of cells you use, how you treat them, and what you do with them. As recent reports suggest, this can be as dangerous and deadly as any drug.


As to point #1, I am still working on my list of products which I hope to publish soon for all to see and review.

As to point #2, I hope some of you will comment on how to best define 'product' for this discussion. There is a similar and very informative discussion thread in the LinkedIn Cell Therapy Industry Group focused around different therapeutic business models. Although the question is framed differently, the discussion hinges on similar distinctions and issues.

As always... I reserve the right to be wrong. I welcome any and all feedback. My only goal here is an informed and informative exchange of ideas and information.


Friday, February 20, 2009

Cell Therapy Industry HiLites 2009-02-20

Before we get started, here's some good advice:
  • renew your membership or join ISCT (
  • 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 a
nd 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.


This issue is sponsored by the company setting a new standard for what you can expect in fresh cell and tissue storage.

You owe it to your cells to find out what they know.

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 (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 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) ...


No news is not really good news here.


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.

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.

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.

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.

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...

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.

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.

* 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>> .

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...

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.


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


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.

Friday, February 13, 2009

Cell Therapy Industry HiLites 2009-02-13

A little slower week allowed for a little more in-depth analysis rather than just passing on the headlines. Hope you enjoy...

My post "Regenexx vs FDA 2009" has generated much discussion both on and offline from interested observers, Regenexx patients, and even Dr. Christopher Centeno himself. Some of that discussion has take place at where there is an ongoing discussion thread about the Regenexx therapy and some of it has taken place here in the comments section of the blog. Dr. Cento has now posted an email he sent me last week as a comment to the blog for the benefit of all to see. This will continue to be a very interesting case to watch as the year develops and we see whether or not the FDA is satisfied to let this kind of clinical practice proceed.


I've always wondered who the investors are who, unlike me - despite my irrational optimism about cell therapies - buy public shares in such early-stage companies like GERN or STEM despite them being so many years away from having a commercial product.
Nonetheless, I've always admired Geron's ability to move and capitalize on movements in its share price.

True to its talents, Geron Corporation (Nasdaq: GERN) announced today (Feb 13) the sale of 7.25 million shares of its common stock. The offering is expected to close on February 19, 2009. On February 12, the press release states, "the last reported sales price of Geron common stock on the Nasdaq Global Market was $7.77".

In an article entitled, "Geron's Stem-Cell Hype Soaks Investors", Adam Feuerstein from is reporting the shares were sold at a price of $6.60, a 14% discount to the stock's Thursday closing price of $7.77 and that the spot-financing deal grossed Geron about $43 million. Geron has not yet disclosed the sale price but is expected to so when the financing closes on Feb. 19. Geron shares fell over 14% to below $6.50 in Friday's trading.


A little update on Northwest Biotherapeutics, Inc. (AIM:NWBS and NWBT; OTC BB: NWBO). Some of you will recall that NWBT went public on the AIM market mid-2007. NWBT's lead product is its DCVax® platform technology that it is studying in multiple cancers. DCVax®recently reported some positive interim data in ovarian cancer although their most advanced trials are in prostate and brain cancers.

Last May NWBT announed it had secured a loan of $4 million from Al Rajhi Holdings W.L.L. who held - at that time - in excess of ten per cent of the company's issued and outstanding common stock of the company.

In October the company announced it had entered into a Loan Agreement and Promissory Note with SDS Capital Group SPC, Ltd for $1 million with a maturity date of April 1, 2009. The company anticipated this would get them through November 2008.

In November, the company announced that it had obtained US$1.65 million in debt funding pursuant to Loan Agreements and Promissory Notes with SDS Capital Group SPC, Ltd (“SDS”) and a group of private investors with the Notes maturing April 21, 2009. The company expected this cash would get them through December 2008.

In December, the company announced that it had obtained US$0.5 million in debt funding from Toucan Partners and that these proceeds were expected to fund the Company’s cash needs into January, 2009.

In January, NWBT announced the settlement of a securities class action lawsuit by the payment of a $1 million settlement to be funded out of insurance proceeds. The case alleged that the Company misrepresented certain facts that resulted in the artificial inflation of the price of Northwest Biotherapeutics publicly-traded common stock between April 17, 2007 and July 18, 2007. The Company disputed the allegations of the lawsuit, and denies any such misrepresentation or that the shares of Northwest Biotherapeutics common stock were artificially inflated. Nevertheless the Company announced it was settling the lawsuit to avoid potentially expensive and protracted litigation. The Company also announced that the formal investigation by the SEC into the matter has been closed without any action taken.

Without doubt the lawsuit has severely impacted the company's ability to raise funds. Now that the legal action is settled and the SEC has gone away, their only hurdle is an impossible fund raising market and presumably only weeks left of cash. We will watch with interest.


Osiris Therapeutics, Inc. (NASDAQ: OSIR) announced the final two-year results for the Company's trial evaluating Prochymal(R) for the treatment of acute myocardial infarction. The data showed lasting clinical benefit in heart attack patients. Prochymal is Osirs' proprietary formulation of adult stem cells designed to provide therapeutic benefit by controlling inflammation, promoting tissue regeneration, and preventing scar formation. The phase I double-blind, placebo-controlled study of 53 patients, which evaluated safety and preliminary efficacy, found heart attack patients receiving the intravenous therapy had lower rates of adverse events and significantly improved heart function. Study findings included:
  • The trial met its primary endpoint demonstrating safety of Prochymal in the acute MI setting.
  • Patients receiving Prochymal had fewer adverse events compared to placebo. A lower percentage of patients treated with Prochymal required repeat hospitalization.
  • Patients receiving Prochymal had reduced incidence of cardiac arrhythmia. Patients receiving Prochymal had a significant and durable improvement in cardiac function.
"We are now advancing this program into a larger Phase II trial, focusing on patients with more severe heart damage," said C. Randal Mills, Ph.D., President and CEO of Osiris Therapeutics.


New Zeala
nd's Living Cell Technologies (ASX:LCT, OTCQX: LVCLY) has reported some interim results from its Russian clinical trial of its DIABECELL® implants for insulin dependent diabetes showing signs of sustained benefit. DIABECELL® is LCT's encapsulated porcine insulin-producing cell product designed for the treatment of type 1 diabetes without the use of immunosuppressive drugs.

A total of seven patients have received DIABECELL® implants, five of whom have had two low dose (5,000 islet equivalents (IEQs) per kg body weight) implants at least six months apart. There have been no remarkable adverse events attributed to double implants. Two patients have received a single higher dose (10,000 IEQs/kg) with no safety concerns to date. Therapeutic benefits have also been observed and are described in the update sent to me but not yet available on the company's website.


Some of my readers and those who listen to my talks aren't fans of the fact I continue to report on and include 'stem cell tourism' companies in my analysis of the cell therapy sector. I understand the reservations and the fact I include them should not be considered an endorsement. My take is that these companies are not going away, they are real business, they are conducting cell therapy as I define it (shodddy or not, credible or not, ethical or not) and and what is needed (per ISSCR) is an informed and informative discussion about how to inject some level of quality assessments over these otherwise unregulated companies and therapeutics.

One such company is Regenocyte Therapeutic. Operating out of Florida where they have their offices and a clinic (I believe for pre- and post-procedural assessments and care), Regenocyte is in the business of recruiting mostly US patients with heart disease for stem cell injections at a clinic in the Dominican Republic for a cost of somewhere around $55,000. They collect blood in a standard blood draw, send it to Israel for the isolation and expansion of stem cells, and then ship the product and patient to the clinic for the stem cell injection. Sounds like your average stem cell tourism business so far but Regenocyte is trying to be different.

Firstly, they don't pretend to be trying to cure everything. They don't have a long laundry list of illnesses they treat. Their website says they focus is on treating patients with heart attack damage, chest pain, poor circulation, leg pain and heart failure. A November press release listed the diseases they address as including
congestive heart failure, cardiomyopathy, peripheral artery disease, coronary artery disease, kidney disease, ischemic heart disease, pulmonary disease and early senile dementia.

This is still a long list but largely cardio-vascular in nature and certainly not nearly as long or diverse as many of these clinics advertise. Having said that, they are not unfamiliar with the kinds of promotions and claims that are the trademark of similar clinics. The leading spokesperson, Dr. Zannos G. Grekos, MD, FAAP, recently boldly stated "we are more than doubling cardiac patients' ejection fraction, improving kidney and pulmonary function, saving limbs from amputation by creating new circulation pathways and most recently reversing the life-threatening effects of metabolic heart disease". Not wanting to stop there he then also announced upcoming plans to treat several neurologically based diseases and macular degeneration.

Secondly, Regenocyte is actively looking for a US manufacturer that will produce their cell product in compliance with FDA's rules governing domestic manufacture and export of their class of product.

Thirdly, they are doing at least some long-term follow-up of patients. “We’ve now treated close to 100 patients with their own stem cells and seen an average 22 point increase in ejection fraction (EF) with a significant improvement in heart failure classification - typically from a Class IV to a Class II status in less than 180 days," Grekos states in a press release this week. The cardiomyopathy treatment study, the first six months of which was published December 2008 in Anti-Aging Medical News, follows patients through one year post-treatment with autologous adult stem cells. Grekos and his team measured patients’ heart function by cardiac nuclear scans, PET scans, and echocardiographs.

Finally, the newly published ISSCR Guidelines has given such clinics a potential stamp of legitimacy. Paul Schwartz, Chief Operations Officer says “The patients’ safety comes first,” he explains. “We adhere strictly to ISSCR (International Society for Stem Cell Research) and WHO (World Health Organization) guidelines...”.


Tissue Genesis, Inc announced they have been awarded a $3.62 million contract from
the U.S. Department of Defense to continue its research and development activities focused on additional treatment options for those suffering from Peripheral Vascular Disease (PVD). PVD is a circulation disorder affecting blood vessels outside of the heart, including vessels supplying the hands, feet and legs, which can cause severe pain.

With the grant, Tissue Genesis will explore transplanting Adipose (fat) derived Stromal Cells (ASCs), isolated from a patient’s own fat using the Tissue Genesis Cell Isolation System, directly into tissues damaged by a low blood supply. This is expected to increase circulation and relieve symptoms of PVD. An improvement in circulation is directed at preventing disease progression, which left untreated ultimately results in 130,000 amputations annually.

According to
Anton C. Krucky, President and Chief Executive Officer of Tissue Genesis, the Department has now awarded the company nearly $24 million to research and develop autologous, adipose derived regenerative medical therapies.


Cord Blood Registry, a services company in the collection and preservation of newborn stem cells from umbilical cord blood, announced the company exceeded $100 million in annual revenue for 2008 – an increase of 28 percent over 2007. In addition, the company surpassed 250,000 total cord blood units in storage, which represents a 26 percent growth rate for 2008. The company also announced that it released its 100th cord blood unit for medical use, a milestone attesting to the rapidly increasing use of a child’s own newborn stem cells (also called autologous use) for medical therapies to help repair damaged tissue and regenerate healthy cells.

In 2008, the company released one cord blood unit every other week for medical use. To date in 2009, the company has released more than two units per week for medical use. The majority of units released – more than 80 percent – have been used to treat the child from whom they were collected. CBR CEO stated that they expect to release more units for medical use this year than they have released in the previous 12 years.

CBR also announced that it is in discussions with three leading medical institutions to launch a clinical study that will evaluate the use of a child’s own newborn stem cells to treat hearing loss caused by an accident or severe illness. The research will be facilitated and coordinated by The CBR Center for Regenerative Medicine which is currently screening potential candidates for the study.


Hongkong's Cordlife and Switzerland's BioSafe SA, have announced they have brought the Sepax automated cord-blood processing system to Hong Kong. Sepax is reported to harvest significantly higher numbers of stem cells from cord blood. To date, over 400,000 cord-blood units in 40 countries have been processed using Sepax. The Swiss-made system is also accredited with health ministries worldwide, including those of Japan, the European Union, Canada and Australia.


NLHBLI has issued a new RFP for PACT centers and administrative office entitled "Cell Processing Facilities in support of the NHLBI Production Assistance for Cellular Therapies (PACT) Program and Support of NHLBI Translational Research in Cell Therapies." The period of performance is for five years beginning on or around November 2, 2009.

Looks like they are wanting to expand to 6 centers in total. I can't imagine the 3 existing centers - University of Minnesota 's Molecular and Cellular Therapeutics facility (MMCT), Baylor College of Medicine's Center for Cell and Gene Therapy (CAGT), and the University of Pittsburgh's Cancer Institute (UPCI) - not getting renewed. What will be interesting is to see who applies and who they choose for the other 3. Will there be any "corporate" service companies that apply and/or are selected?

What's interesting is the fact this is being renewed despite my understanding that at least initially they had difficulty finding ways to spend their money under their mandate as it was initially conceived. This is in part, I believe, why PACT resorted to spending their money on educational type activities. Not that they weren't needed and certainly the identification of that need was also, I suspect, part of their motivation to steer in this direction. Still, according to their most recent newsletter, as of December 2008, PACT had received over 655 application requests for the manufacturing of cell therapy products and while this resulted in over 180 cell products have been administered to patients, it was only from 14 approved projects.

While we're on the subject, one of the useful non-manufacturing outputs from PACT is an abridged list of commercially available cytokines and antibodies. This is not purported to be an exhaustive list but if you see changes you think should be made, let me know - I'll collect your input and forward it on to them.

For those interested, PACT also has a list of cell therapy facility/process/compliance-related SOP's which are available upon request.


ISCT is hosting a two-part validation webinar:
  • (Part 1): Validation and Qualification of Equipment and Reagents. Wednesday, February 18, 2009,12pm - 1pm EST. Speakers:Lizabeth Cardwell MT(ASCP), RAC, MBA, Principle Consultant, Compliance Consulting, WA; Karen Edward, BS, Advanced Cell and Gene Therapy, NY
  • (Part 2): Validation of Processes: Retrospective and Prospective. Wednesday, March 25, 2009,12pm - 1pm EST

So that's the shape I saw the biz of cell therapy taking this week. Hope you got something useful...


Cell Therapy 2009. San Diego. May 3-6.
Attend. Exhibit. Sponsor. Submit your abstract (Deadline: February 200

I'll see you there, right?

p.s. Ok I didn't actually buy a bus ad. I cheated. I used the free online bus ad generator :)

Tuesday, February 10, 2009

Cell Therapy Group & BioBusiness.TV collaborate to bring online coverage of cell therapy content from the 2009 Phacilitate Cell & Gene Therapy Forum

We are back from the Phacilitate Cell & Gene Therapy Forum 2009 and we've captured some highlights, which include Lee Buckler's review, some great interviews, brand new Mash Ups, and 60sec Pitches. Take a look!

The BioBusiness.TV Team.

Lee Buckler's Cell Therapy '08 Review and '09 Outlook.

Some of the exciting things we've seen in 2008 are:
  • the involvement of pharma in cell therapy, investing like they haven't before, developing cell therapy products as drugs, and not just tools (including companies such as Pfizer, GSK, Roche, and Novartis)
  • the number of late stage companies in the sector such as Osiris (see: Osteocel / NuVasis, and Prochymal + Chondrogen / Genzyme deals), Dendreon, and others
  • the financing, partnerships and M&A activity with $400M private equity investment, $100M M&A, and $1.8bn in non-M&A deals.
Some things to watch for in 2009 are:
  • some of the late stage companies (Osiris and Dendrion - i.e. Provenge results in April)
  • the struggling cell therapy companies and how they will find cash (M&A, Government, VC?)
  • the role of the new Obama administration and the public pressure, interest, and enthusiasm for cell therapy.
Watch Program »

Harvard Steps Into the Cell Therapy Funding Gap with a Mission for Academic Research to Get to Patients.
Brock Reeve explains the functioning of the Harvard Stem Cell Institute (HSCI). The HSCI is looking to make the bedside-to-bench and bench-to-bench loop in a way that is unequaled anywhere, with the university and its 11 affiliated hospitals, drawing resources from the various schools (law, business, government, divinity). Brock tell us about about the HSCI partnership with GSK, as well as the other relationships they are seeking and building at the moment.

Watch Program »

Roche's Vertes on Big Pharma's Interest in Cell Therapy.Alain Vertes of Roche presents the interest of his company in the cell therapy. He highlights the main points of his panel presentation:

1. Cell therapy is not a passing fad
2. Cell are not just transplants, they can also be drugs
3. Paradigm shifting applications for cell therapy
4. Protecting intellectual property
5. Potential for stunning efficacy and low risk of side effects.

Watch Program »

US and EU Regulatory Synergies, and EMEA Committee for Advanced Therapies.
Christopher Bravery comments on the new committee for advanced therapies of the EMEA, and its impact on the development of cell therapy in Europe. Christopher also reflects on the similarity between US and European regulatory environments, and the importance of considering that in planning pivotal studies. He also gives us his definition of Cell Therapy and explains the business of ERA Consulting.

Watch Program »

'Mash UP'. Delegate responses to the following questions:

60sec Pitches

Interested in your company sponsoring future content like this focusing on the cell therapy market for BioBusiness.TV? Interested in sponsoring a cell therapy "channel" on the site? Contact Lee Buckler @ [the] Cell Therapy Group.

Friday, February 6, 2009

Cell Therapy Industry HiLites 2009-02-06

Following on the heels of FDA's approval for Geron's trial, I suppose it's not surprising that TIME magazine put stem cell research as its cover article. But while stem cell research enjoys the glory and any stock even remotely related to cell therapy is enjoying a bullish run, CIRM - one of the efforts responsible for keeping stem cell research alive in the US during the last 8 years - is being threatened by California's crushing debt.

It was an interesting week at the Phacilitate Cell & Gene Therapy Forum last week. In some ways it was a little Dickensian - the best of times; the worst of times. On one hand we had Genzyme-Osiris talking about the biggest deal ever in cell therapy, both Osiris and Dendreon potentially being on the verge of the first cell therapy BLA approval in a decade, and the pharma industry coming out of the closet speaking about their belief in cells as therapies not just tools for discovery or toxicity testing. On the other hand, the fact that money has pulled a disappearing act on many who thought they had it or been freeze-dried in the pockets of those who still do, makes it nervous times for a bulk of the industry. This is a sector that may look drastically different at the end of the year than it did at the beginning and while this will make for tough decisions, may impeded some progress, and generate many a sleepless night... an industry re-org may not be an entirely bad thing.

This issue is sponsored by folks that sell stuff their customers honestly want to keep a secret.
If you knew what they know, you would know you can change the way you store your cells. You wouldn't be thinking the yield you're getting from your cellular source material and cryopreserved products is just fine - not worth investigating.
You would know that BioLife's solutions (now both the subject of an FDA Master File) could very well improve your product, decreased product failures, and maybe even lower your costs. But then if you knew that, you'd already be a customer!

You probably owe it to your cells to find out what they know.

I want to take a moment to correct something. In December I said that while I was a little confused by their recent press release, it looked to my like Wuxi-Apptec was getting out of the cell therapy manufacturing business. I took the opportunity at last week's Phacilitate meeting to get some clarification. Indeed, I was wrong. I asked WuXi AppTec, VP, Philadelphia Operations, Garry B. Takle, Ph.D. for clarification. I'm happy to share with you his reponse below:

The recent closure of the recombinant protein and monoclonal antibody manufacturing bioreactor suites in the WuxiAppTec, Philadelphia facility does not affect the continued focus on and expansion of cell therapy manufacturing, cell bank manufacturing and biologics testing programs at the site. WuXiAppTec has taken the strategic position that cell therapy products are likely to provide significant outsourcing revenue in the short and mid term, as these more novel products become firmly established and better accepted.

WuXiAppTec has been in the cell therapy business for more than 3 years and intends to use the experience gained during this period to attract a broader portfolio of cell therapy clients. WuXiAppTec has so far completed 5 cell therapy manufacturing projects, including both allogeneic and autologous cell therapies.

In addition, WuXiAppTec currently performs testing for more than 15 cell therapy clients and manufactures more than 50 cell banks per year. Combined with considerable experience in medical device testing and manufacture, and in the production of tissue-based products at the WuXiAppTec St Paul facility, the WuXiAppTec Philadelphia site provides the GMP/GTP cell expansion expertise to develop and manufacture a wide range of cellular therapies and combination products.


Cell therapy company Garnet Biotherapeutics, developing products for scar reduction after surgery or dermatological procedures, announced the close of a $10.4 million round led by SCP Vitalife Partners II, L.P. Garnet will use the proceeds to fund Phase II clinical trials of its proprietary human adult bone marrow-derived cells, as well as manufacturing and development. Safeguard Scientifics, Inc. and Alliance Technology Ventures also participated in the financing.

It is clearly too early to do the 3-count for Bioheart, Inc. (Nasdaq:BHRT) which announced private funding commitments of up to $7 Million. The company has entered into a non-binding letter of intent with Organic Business Alliances, LLC ("Organic") pursuant to which it would invest approximately $1.5 million in Bioheart under its current offering under Regulation D and, subject to Bioheart achieving certain specified milestones, invest up to an additional $5.5 million on terms substantially the same as those of the offering. The investment by Organic is subject to approval of the boards of directors of both Bioheart and Organic and mutually acceptable definitive agreements.

Pluristem Therapeutics Inc. (NasdaqCM:PSTI) (DAX:PJT), a bio-therapeutics company dedicated to the commercialization of non-personalized (allogeneic) cell therapy products for a variety of degenerative, ischemic and autoimmune indications, announced that on January 29, 2009, the Company entered into definitive agreements to sell restricted common stock and warrants for aggregate gross proceeds of $1,200,000.

The company also recently announced that it had received approval (in the form of a declaration) from Biotec Services International Limited, stating that Pluristem's Investigational Medicinal Product (IMP), PLX-PAD, is manufactured in accordance with standards of Good Manufacturing Practice (GMP), equivalent to those applied in the EU. Biotec Services is an international clinical trials supply company providing release services of the IMP into the European Union by a Qualified Person (QP). Upon IND and IMPD clearance by the regulatory authorities, Pluristem plans to initiate clinical trials in Europe and in the U.S.A., administering PLX-PAD to patients afflicted with critical limb ischemia, which has not responded to traditional medical or surgical interventions. They've invested ~$2M building in their facility and team to get them to the point of a successful audit of the manufacturing site by a Qualified Person. <more>

Following the implementation of the Clinical Trials Directive 2001/20/ EC in May 2004, any company wishing to undertake European clinical studies must have a Qualified Person (QP) release supplies of Investigational Medicinal Product (IMP) that have been manufactured outside the EU for use in European clinical studies. The QP conducts audits of manufacturing facilities outside the EU, ensuring that each batch has been manufactured in accordance with current Good Manufacturing Practices (cGMP) guidelines.

Organogenesis, Inc has been awareded a two-year, $7.4 million grant from the Massachusetts Life Sciences Center to support the firm’s expansion in the state. Organogenesis, a Canton, MA-based maker of living cell therapies for damaged tissues, has purchased two buildings in Canton and plans to grow its Massachusetts workforce from 220 today to 500 workers, according to the Life Sciences Center. Apligraf® has been used to treat many thousands of patients and is covered extensively by Medicare, Medicaid and by 350 private payers in the U.S.

According to their recently filed Form 10-Q (Quarterly Report), Aastrom Biosciences (Nasdaq:ASTM)
executed a $15 million common stock purchase program with Fusion Capital Fund II, LLC (Fusion Capital) on October 27, 2008. They have the right, over a 25-month period, to sell shares of common stock to Fusion Capital from time to time in amounts between $60,000 and $2 million, up to an aggregate of $15 million, when they choose to do so, based on the terms of the agreement.

In an accompanying press release, Aastrom outlined a number of recent and anticipated events including the fact the FDA put their dilated cardiomyopathy (DCM) trial on hold Feb 2 for reasons which appear associated with the anesthesia administration.

ThermoGenesis Corp. (NASDAQ: KOOL) has reported second quarter results in whixh the company records the second quarterly sequential increase of 36%. For the quarter ended December 31, 2008, the Company reported revenues of $6.1 million, a 12 percent increase over revenues of $5.5 million in the same period a year ago. Disposable revenues in the quarter were $3.5 million, a 35 percent increase over disposable revenues of $2.6 million in the second quarter of fiscal 2008. Disposable revenues associated with the Company’s core AXP AutoXpress Platform™ (AXP™) and BioArchive® Systems offering increased by 56 percent year-over-year as AXP bag set volume in the quarter was 26,500 versus 20,000 in the second quarter a year ago.

The ThermoGenesis' MarrowXpress (MXP) is now being used to concentrate stem cells from bone marrow in an ongoing Phase II clinical trial being conducted at the University of Naples in Italy to study the effect of bone marrrow derived mononuclear cells on patients with critical limb ischemia (CLI). <more> <analysis>

Millipore Corporation (NYSE: MIL), a provider of technologies, tools and services for the global life science industry, announced that it has entered into a $22M agreement to acquire Guava Technologies, a provider of bench top cell analysis systems. The acquisition follows the distribution and co-development partnership the two companies announced in March 2008. Millipore says that its recently announced deal to acquire Guava Technologies will let it develop new kits for stem cell research. <more>

BioLife Solutions, Inc. (OTC Bulletin Board: BLFS), a leading developer and marketer of proprietary GMP hypothermic storage and cryopreservation media products for cells, tissues, and organs, announced record revenue and new funding to support internal manufacturing scale-up already underway to support increased product demand. The company registered record revenue for the fourth quarter and full year 2008. Preliminary fourth quarter 2008 revenue was $417,818, an increase of 36 percent from the third quarter of 2008, and 40 percent over the fourth quarter of 2007. This includes initial orders from nearly 30 new customers. Preliminary full year 2008 revenue was $1,326,772, an increase of 36 percent over 2007 fiscal year revenue.

Biolife also landed $1.4 million in credit funding from two shareleholders for operations and the completion of construction and validation of a new manufacturing facility.

To complete its triage of announcments, the company announced the launch of its new quarterly newsletter BioPreservation Today. They hope the publication will be a forum for sharing knowledge about optimizing biopreservation protocols and processes, to maximize the yield and function of cells and tissues in research and clinical applications.

Healthcare of Today, Inc ("Healthcare of Today"), announced the $100M acquisition of Regenetech, Inc ("Regenetech"). The Regenetech acquisition is one of a series of major acquisitions made by the holding company recently. Last week Healthcare of Today announced that it had obtained Advanced Developers, a builder of resort-like senior facilities in production in Florida and South Carolina. Prior to that, the organization had entered into an agreement to acquire another $19.4M medical facility in Agoura Hills, California.

Healthcare of Today, formed in May of 2008, is a holding company focused on acquiring and developing companies primarily within the healthcare industry. Through its subsidiaries, Healthcare of Today owns a variety of businesses including: nurse staffing, insurance, pharmaceuticals, residential care facilities for the elderly, assisted living facilities, skilled nursing facilities, senior communities, home healthcare services, senior fitness, real estate brokerage/relocation services, adult daycare, a private chef network, a culinary institute, healthcare information technology, nurse education, and biotechnology.

ch® has concentrated its research efforts on development of umbilical cord blood and peripheral blood expansion, increased regeneration of bone for orthopedic uses, and production of biomolecules. Regenetech®’s business purpose is to commercialize adult stem cell expansion technology by developing stem cell and tissue regeneration technology, patenting it quickly and either licensing or establishing joint ventures to commercialize the technology to generate revenue.

Last year Regenetech announced it could achieve a 60-fold increase of adult stem cells through its cellXpansion™ process, namely CD34+38- peripheral blood progenitor cells (adult stem cells). These results were reportedly achieved through the continued development of cell culture conditions in Regenetech’s proprietary and patented Intrifuge™ cellXpansion™ technology. As I recall from listening to a presentation last May, the core technology is essentialy an electro-magnetic field placed around a bioreactor.

The company was founded in April of 2002 as BioCell Innovations. In May of 2002 the company acquired its original patent licensing rights through a novation from NASA. In May of 2002 Regenetech® entered into a Sponsored Research Agreement with M.D. Anderson Cancer Center in Houston, Texas. Regenetech® filed its first patents in August 2002. The company name was changed to Regenetech®, Inc. in November of 2002 in order to begin developing trade name value. Stage 1 research was fully completed in January 2003. Regenetech® licensed its first intellectual property for treatment of Sickle Cell Anemia. In April 2004 Regenetech® Licensed an additional two (2) patents from NASA relating to advanced bioreactor technology.
In April 2004 Regenetech® entered into a Reimbursable Space Act Agreement with NASA to continue development of adult stem cell expansion. In January 2005 Regenetech® confirmed its significantly expanded adult stem cells were free from cancer risks and had no genetic modification. In 2005-2006, Regenetech® expanded its research at NASA and several universities and completed the filing of its first73 patent applicati

The company's former CEO Dr. David Bonner, who appeared at one point to be steering the business toward involvement with off-shore commercial stem cell transplant clinics, had a parting of ways with the company a year or so. He then opened up Stematix, Inc with some of his former team. Stematix is in business to "support and establish fully operational stem cell banks and therapy clinics around the world."

Intercytex Group plc (LSE: ICX) ("Intercytex" or "the Company"), a developer of regenerative medicine products, has implemented restructuring actions to reduce cash burn. Despite the very positive progress being made on all projects, with the financial markets in their current state, the Company will shortly commence a 30 day consultation period with employee representatives proposing a reduction in headcount at the Company's facilities in Manchester UK and Boston, USA of around 50% from the current level of 76 employees. The reduction in workforce will extend the Company's existing cash resources to fund operations until around the end of 2009. The measures are expected to be implemented with effect from March 2009.


Advanced Cell Technology, Inc. (OTC:ACTC) provided a corporate update in which it announced that it has accelerated its efforts to file an IND for its retinal pigment epithelium (RPE) cells program for the treatment of diseases of the eye in light of today’s decision by the U.S. Food and Drug Administration to grant clearance for a stem cell company to begin trials for the world's first study of a human embryonic stem cell-based therapy for people. The Company is close to securing the necessary funding which would allow it to make the requisite filings during the summer of this year

Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced today that its collaborators at the University of Pennsylvania (Carl June) have opened a Phase 1 clinical trial to evaluate SB-728-T for the treatment of HIV/AIDS. SB-728-T is produced by specifically modify the patient's own CD4+ T-cells, the principal target of HIV infection, with a one-time exposure of the cells to CCR5-specific ZFNs. This generates a population of T-cells that lack the CCR5 receptor, are resistant to HIV and can be infused back into the patient to provide a reservoir of HIV-resistant functional immune cells and, more importantly, may expand and provide an HIV immune response. specifically modify the patient's own CD4+ T-cells, the principal target of HIV infection, with a one-time exposure of the cells to CCR5-specific ZFNs. This generates a population of T-cells that lack the CCR5 receptor, are resistant to HIV and can be infused back into the patient to provide a reservoir of HIV-resistant functional immune cells and, more importantly, may expand and provide an HIV immune response." The primary objective of the study is to evaluate the safety and tolerability of SB-728-T. In addition to safety monitoring, data will be collected on the expansion and persistence of ZFN-modified cells, CD4+ cell counts and viral load.

According to a online publication in Molecular Therapy, Stratatech Corporation has engineered a skin substitute with potent anti-infective function. The product is a genetically modified version of its StrataGraft® living human skin substitute designed to actively fight costly bacterial infections that routinely develop at the site of burns and other severe skin injuries, such as skin ulcers. Stratatech’s skin-substitute innovation reportedly enables the immediate topical delivery of a potent anti-infective that actively inhibits bacterial growth and promotes regrowth of the patient’s own cells. The anti-infective capacity of Stratatech’s genetically-engineered tissue, which is being developed and commercialized by the company as ExpressGraft™ Enhance skin substitute was generated using a non-viral vector, or carrier. The company believes it is the first time a virus-free approach has been used to genetically modify a living, cell-based tissue substitute

Therakos, Inc. announced that Health Canada has cleared the THERAKOS(TM) CELLEX(TM) Photopheresis System for the palliative (reducing the severity of symptoms) treatment of the skin manifestations (appearance) of cutaneous T-cell lymphoma (CTCL) that are unresponsive to other forms of treatment.

Stem Cell Innovations, Inc. (OTC Pink Sheets: SCLL) appears to be working on a liver assist device to support patients waiting for transplant. The company has not made a formal announcement that I can find and the company's website is woefully out-of-date but the device was described in a paper published in the most recent issue of Current Gastroenterology Reports. Medical News Today was able to get the company to comment for an article they did highlighting the article: "There are currently three times as many patients on the waiting list for liver transplantation as there are organs available and few ways to stabilize them if they enter an acute phase of their disease," said Kelly, CEO of Stem Cell Innovations. This second generation device, based on the PluriCells, "combines the safety of primary hepatocytes (normal liver cells) with the standardization of a cell line," continued Kelly. "We're building on what we learned from our earlier device which utilizes the C3A cells that form the basis of Stem Cell Innovations' ACTIVTox(R) drug discovery products. We are one of the few companies that can approach this problem from both sides: from the stem cell and from the adult liver cell. We are using our PluriCell(TM) system to understand the requirements of the liver stem cell and our ACTIVTox system to understand the requirements of the mature cell."


Privately held SkinMedica of Carlsbad says it has filed a patent infringement lawsuit against new San Diego startup Histogen and Gail Naughton, its founder and CEO. The lawsuit, which was filed in federal court in San Diego, alleges that Histogen and its affiliated Histogen Aesthetics business infringe on two SkinMedica patents related to proprietary conditioned cell media technology. SkinMedica says its complaint asks for unspecified relief for the “misapprorpiration of SkinMedica trade secrets and confidential information by Histogen.”

International Stem Cell Corporation (OTCBB: ISCO) continued its recent publicity campaign with a letter to shareholders outlining recent development and plans for the company and their human parthenogenetic stem cells. The company is thrilled to have had their name dropped in a recent article in the Economist along with corporate pioneers like Geron & ACT.

Neuralstem Inc. (AMEX: CUR) has nailed down a key patent for its core technology, which grows neural stem cells from the brain to replace damaged spinal cord cells. The patent comes in time for Neuralstem’s first clinical trials, planned for this year if the Food and Drug Administration gives them the green light. The Rockville company intends to test the ability and safety of injecting fetal stem cells into the spinal cords of patients suffering from amyotrophic lateral sclerosis, more commonly known as Lou Gehrig’s Disease. Neuralstem filed its request in December to launch its first human clinical trials this spring. It expects to hear the FDA’s decision by the middle of next month, but another competitor’s recent news has raised its hopes.

Bio-Matrix Scientific Group (OTCBB: BMSN) ( has entered into a cell processing and storage contract with both NeoCells, Inc. and AdultCells, Inc. (ACI; Pursuant to this Contract, BMSN has agreed to (a) cryogenic banking and processing of umbilical cord blood and adult peripheral blood stem cells of clients from both NCI and ACI and (b) cryogenic banking and processing of menstrual blood and other human stem cells of clients from both NCI and ACI upon BMSN’s approval. Fred Fitzsimmons, CEO of NeoCells, Inc. and AdultCells, Inc., envisions “the developing relationship between BMSN, NCI and ACI leading to the establishment of the premier stem cell cryogenic storage company in the U.S.” he said.


Ex-FDA regulatory cons
ultant Darin Weber (aka "Regenerative Medicine Guru") now of the Biologics Consulting Group, has posted on his blog a number of useful presentations and articles he did in 2008. It's worth checking out.

You won't find a press release about this anywhere but the only weekly publication dedicated to news in the cell therapy sector, Cell Therapy News (which I founded back in 2001 as an email to colleagues and grew to ~11,000 subscribers) has now been subsumed by the Stem Cell Technologies' marketing department. The publication is no longer accepting outside advertising. Cell Therapy News is a news amalgamation service and does not do original and/or editorial content. The publication's objectivity should not be compromised unless they refuse to include press releases from competitors. Rumor has it this is indeed the case. Disappointing if true.

If you're interested in getting into the mind of
Stem Cell Technologies' owner and founder, Allen C. Eaves, you'll find the rambling interview of him recently posted by Q1 to be an interesting read.

Monya Baker from The Niche, always does such a nice job of collecting primary and divergent sources on a topic. She's done the same on her second post about Geron. If this is a trial, company, or stock in which you are particularly interested, you'll want to check out her collection of articles.

This past week's GEN podcast was "Stem Cell Therapies on the Rise" by Linda Powers, Cofounder and Managing Director of Toucan Capital, which has 16 stem cell or regenerative medicine companies in its portfolio. Linda specifically addresses the issue of how the FDA's decision on Geron's IND might boost the development of stem cell therapies and speculates on what may have influenced the agency's decision to give Geron the go-ahead for a trial at this time. Powers also discusses why all the attention on human embryonic stem cell research has given short shrift to work with human adult stem cells and provides specific examples of the successful application of adult stem cells to treat human diseases. Powers describes what's needed from the financial, political, regulatory, and public acceptance arenas to make stem cell and regenerative medicine part of an expanded armentarium of therapeutic approaches in applied and clinical medicine. She also explains why the establishment of a biomanufacturing industry for the production and processing of stem cells and other living cells could give rise to a new and significant business segment of the American economy.

NIH/NHLBI and PACT have announced a workshop on 23-24 April entitled "Converging Concepts in Cell Therapy". This workshop will be held at the National Institutes of Health (NIH), Natcher Conference Center in Bethesda, Maryland.

University of Minnesota is hosting a professional short course, "Preservation of cells, tissues and gametes" to be held May 18-20, 2009.


I was very pleased to see a 1.5-page article entitled "Stem cell alliance" in the January 2009 issue of R&D Directions magazine, a very pharma-focused publication related to 'pharmaceutical research and development'. The >$1B deal Genzyme-Osiris deal has caught the attention of many in the pharma sector who heretofore have believed the sector too immature to mean real business.

That ends a hectic two-weeks.
Sometimes conferences and paying work get in the way of blogging. I can't really complain. But that's why this is later than my usual Friday pub date. I have every intent to get back to the weekly schedule on Friday. We've had a good run of new subscribers sign up this week. Welcome ya'll. If you learn anything here we hope it's that cell therapy...means business! :)