Cell Therapy Industry HiLites 2009-05-26

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

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

Down to business...

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

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

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

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

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

FINANCIAL

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

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

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

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Cord Blood America, Inc. (OTCBB:CBAI) has received a commitment for up to $2.3 million of new funding to acquire or build its own state-of-the-art laboratory for the storage of multiple stem cell products including umbilical cord blood stem cells. Less than two years ago the company signed a deal with Progenitor Cell Therapy LLC to process and store their stem cell units on a contract basis. Now CBAI says having their own facility will over the long term reduce their costs for both the processing and storage and additionally allow CBAI the flexibility and capacity to pursue new sources of revenue such as the storage of adipose tissue and peripheral blood stem cells processing and storage much easier than under the current structure of outsourced relationships.

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Core Dynamics announced it has recently closed on a new financing round of US$17.9 million institutional and private investors. The money will be used to further develop the company's process for freeze drying human stem cells to be stored at room temperature.

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Bioheart, Inc. (OTCBB:BHRT) announced today that its common stock is now being quoted on the OTC Bulletin Board (OTCBB) under the trading symbol "BHRT," the company's original ticker symbol.

CLINICAL

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

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

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Little-known, Memgen, LLC will be presenting results from a recently completed phase I clinical trial of its novel active immunotherapy product, ISF35, in patients with high-risk, progressive chronic lymphocytic leukemia (CLL), at next week's ASCO meeting. According to the study's principle investigator, Dr. Castro, one injection with no chemotherapy resulted in durable reductions in lymph nodes and spleen size in most patients and three of fifteen patients with rapidly progressing disease did not require any further treatment for more than one year. Based on the results from this single injection study, a phase II trial evaluating multiple intranodal injections of ISF35 in CLL has begun funded by - of all things! - the Food and Drug Administration at UCSD. The company believes the product is also positioned for use in lymphomas and solid tumor cancers.

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Aderans Research Institute Inc. (ARI) announced it has launched Phase 2 of its clinical study on cell-based hair regeneration for men and women. The company's research is focused on developing a state-of-the-art tissue engineering solution to the regeneration of hair, taking actual hair cells--fibroblasts and keratinocytes, the two primary cell types within hair follicles--and promoting their growth in controlled laboratory environments. The research teams then recombine them and these "combined hair cells" are then placed in the patient's skin, where they are expected to elicit hair growth.

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Cytori Therapeutics, Inc. (NASDAQ:CYTX) completed enrollment in the first study to investigate adipose derived stem and regenerative cells in chronic heart disease. The trial, named the PRECISE study, was designed as a double-blind, randomized, placebo controlled, dose escalation study specifically enrolling patients suffering from an advanced form of chronic heart disease, known as chronic myocardial ischemia, for which there is no generally accepted treatment. The trial enrolled 27 patients in a study involving the patients’ own cells extracted from adipose tissue and processed for delivery at the point of care using Cytori’s Celution® System. The cells were then injected back into the patients using the NOGA® XP System (Biologics Delivery Systems, Cordis Corp., a Johnson and Johnson company). Primary endpoints were safety and feasibility of Cytori’s Celution® System as part of a novel procedure for chronic heart disease.

A major attribute of the Celution® output is that it is comprised of multiple cells types. This, the company believe, contributes to multiple mechanisms of action, and thus increases the potential to restore heart function. The Celution® System used in PRECISE was configured specifically for cardiovascular disease, including proprietary processes and enzymes needed to achieve a level of purity required for vascular delivery.

COMMERCIAL

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

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Celsense, Inc. has announced the formal opening of its new and expanded R&D facility said to be a key component to Celsense’s commercialization strategy for its pre-clinical and clinical-grade molecular imaging agents used to non-invasively visualize and measure cellular activity and biodistribution. The company is now actively bringing both their lead research and clinical-grade cellular and molecular imaging agents to market over the coming months and is said to be collaboration with several academic and industry parties currently evaluating our products for potential use in their discovery research or clinical protocols.

Their clinical-grade Cell Sense reagent is a fluorocarbon tracer agent used to label cells in vitro then transplanted thus enabling investigators and clinicians to non-invasively track the administration and delivery of therapeutic and diagnostic cells in vivo using MRI. Applications include tracking therapeutic cells in regenerative medicine and immunotherapy applications, and observing localized immune system response by tracking populations of immune system cells. The research-grade V-Sense is an injectable fluorocarbon MRI tracer agent that labels leukocytes in situ, enabling the direct, non-invasive observation of immune system response and localized inflammation. Applications include observing change in immune system response to therapeutics and mapping localized disease such as certain cancers and infections.

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

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

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

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

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

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

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

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

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

**

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

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

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

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

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

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According to the Seattle Times which played a critical role in exposing what is now alleged to be potential fraud, CellCyte Genetics, "left a cashless zombie after the stock-touting campaign that lifted its value to $400 million faded away, says it has reached a tentative settlement in the Securities and Exchange Commission (SEC) inquiry into its activities" but it still faces a criminal probe and the "number of lawyers embroiled in the company's legal troubles have now outnumbered the company's peak work force".

MISCELLANEA

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

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

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

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

Sign-off

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

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

Remember. Cell Therapy Means Business.

Cell Therapy Industry HiLites 2009-01-02

Happy new year everyone.

2009 feels like it has the potential to be the somewhat overlooked precursor to the 2010 milestone - not that that's bad just perhaps a "building" year rather than a champagne-popper. Whatever it turns out to be I wish you all a happy and prosperous year.

Based on how slow this week was, I fear next week. I predict a killer backlog of pent-up news on its way. In any event, here's what trickled out this week...

Last week Medistem announced it had filed an IND for use of their new endometrial regenerative cells (ERC) for treatment of critical limb ischemia.

ACT & CHA Biotech have rethought the name for their new joint venture (formerly announced as "Allied Cell Technology" the acronym for which is also 'ACT') - opting instead for the more distinct but lengthy, "Stem Cell & Regenerative Medicine International".

Stem Cell Sciences plc, which is listed in Australia and the United Kingdom announced that it had received a GPB200,000 ($A426,348) loan to use for working capital. In return, the third-party lender has been granted an exclusive period to conduct further due diligence in relation to Stem Cell Science's business and assets. Stem Cell Sciences said it was not in talks with any third parties that might lead to an offer for the issued share capital of the company. Stem Cell Sciences, whose shares have been suspended from quotation since November 26 pending a review of the company's financial position and strategic options, last traded at 15 cents.

Wading now into deep speculation, this tickles the senses like a move Stem Cells Inc might make (I have no information upon which to base this except their past actions) though the SCS assets would not seem to fit with STEM's portfolio. In that respect, this would seem like more of a natural acquisition by Pfizer which did a 5-year deal with SCS in November. I suspect we shall soon see...

Just to make things a little more curious, SCS later announced publication in Cell of a pioneering technique for creating authentic ES cells from rats. They believe the publication to be the first in which germ-line transmission from rat ES cells has been definitively demonstrated. It uses technology licensed exclusively to SCS from the University of Edinburgh and developed by Professor Austin Smith and his team, now at Cambridge University.

Alright this isn't a business item but it has business ramifications and I've discussed this issue in my blog a number of times. "Definite and measurable neurological and ophthalmological improvement." That was the clinical observation of ophthalmologist, Dr. Jack Guggino, in comparing 5-year old Xavier's post stem cell treatment exam results with those of a pre-treatment baseline exam. Xavier, diagnosed at age 2 with optic nerve hypoplasia, was flown to China for a controversial stem cell treatment from the sort of clinic that is drawing much criticism from the global scientific community. These clinics are criticized for, among other things, lack of transparency, formal clinical trials, peer-reviewed publications, and patient follow-up to track long-term clinical results. Recent criticism has suggested results are exaggerated and risks downplayed. Nevertheless, if Xavier were my child what would I do? Ok perhaps it would take something terminal and I'm not saying I would, I'm just sayin'...

Just to polish off the year with a little more successful fundraising news, International Stem Cell Corporation (OTCBB:ISCO) announced it has received the first $1 million tranche of an anticipated private equity financing of up to $5 million to be funded over the next several months. The total amount of the financing is intended to allow the Company to retire its existing secured debt and fund operations of the Company as it moves forward with planned pre-clinical trials in the first quarter of 2009.

Watch for a blog coming soon adding up my totals for how much was raised this year by companies in the space.

In a curious case of the company vs the newspaper, the Seattle Times reported on Dec. 24 that CellCyte Genetics had shut down and was unable to pay rent on its Bothell headquarters citing the company's delayed SEC filing. The company, whose shares trade over-the-counter and in the Frankfurt Stock Exchange, saw its value soar past $400 million last year but since plummeted in the midst of questionable activity currently under investigation and the subject of litigation. CellCyte's shares plummeted in January after The Seattle Times published stories describing the stock-promotion efforts and inconsistencies in the résumé of CellCyte Chief Executive Gary Reys. Clearly the Times and CellCyte are not on talking terms because on Dec. 29 Cell Cyte issued a press release saying the Times had it all wrong citing an Aug. 14 press release in which the Company reported progress in its bioreactor business segment and generally described its development plan to commercialize its bioreactor product line. CellCyte reiterated its intent to execute this development plan in 2009.

The company's Form 10-Q, filed Dec. 22, states:
"As of September 30, 2008, the Company had a working capital deficit of $897,402, and an accumulated deficit of $9,890,982 incurred through September 30, 2008. The Company has no revenues. Management forecasts operations during the coming year will need approximately $2,500,000 in additional working capital, which is expected to come from issuance of convertible notes and private placements of stock."

The filing laid out detailed plans for the company over the next 12 months but also stated the following: "As of September 30, 2008, we had cash in the amount of $5,734 and a working capital deficit of $897,402. Our planned expenditures over the next 12 months are expected to amount to approximately $2,500,000 and will exceed our cash reserves and working capital. We presently do not have sufficient cash to fund our operations and have curtailed significantly all activities. We anticipate that we will require additional financing in order to pursue our plan of operations for the next 12 months. There can be no assurance that we will obtain any additional financing in the amounts required or on terms favorable to us. If we are unable to obtain additional financing, we may have to abandon our business activities and plan of operations."

The Seattle Times may be guilty of a little prognostic reporting here but it certainly does seem like CellCyte will have to pull a wee little rabbit out of the hat to keep things going. Having said that, I've certainly heard the premature predictions of the imminent demise of many a cell therapy company before only to watch them 'pull a phoenix'. I like it when that happens.

I don't pretend to fully understand the Cytori patent portfolio and after the legal wrangling settled who ended up with what for what but Cytori announed the issuance of U.S. patent # 7,470,537 (the ‘537 patent) covering adipose-derived stem and progenitor cells to the University of California. The patent application containing these claims is jointly owned by the University of California and the University of Pittsburgh. The composition of matter patent is licensed to Cytori through its agreement with the University of California. The cells covered by the issued claims are believed to encompass a clinically important subpopulation of cells within adipose tissue.

BIO says one in four of the 370 publicly traded U.S. biotech companies have less than six months of cash on hand. But it's not just industry that's impacted by the economic crunch. The global financial crisis may do what opponents of California’s $3 billion state-sponsored stem cell research experiment could not: dry up funding. To keep the money flowing, later this month CIRM will weigh a contingency financing plan that could include bond anticipation notes and a private placement with major philanthropic backers.

And that brings me to my challenge to you all. I know money is tight but it is even more important in times like this that we remember to support the non-profits that support life as we know it for so many. This is true in your local community, on a global scale and it is also true in the industry in which you work. The non-profit organizations that provide critical support to the cell therapy industry need your financial support and your volunteer contributions. This week I announced that I've committed the Cell Therapy Group to supporting ISCT by way of a 2009 corporate membership. Please consider doing the same.

And that, my dear readers, polishes off 2008 and the first couple days of 2009. That's the cell therapy industry the way I saw it over the holiday season.

As Robert A. Preti is fond of saying... "Be careful out there".

Cell Therapy Industry HiLites 2008-12-19

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

For the week before Christmas this was one busy week!

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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


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

--Lee

Cell Therapy HiLites 2008-11-28

For what is typically a slow business week in the US, the cell therapy sector had some big news. More money, more deals, and some interesting developments to watch.

Argos Therapeutics completed a second and final tranche of a $35.2 million Series C financing from new and existing investors (the first tranche was completed in April 2008) to support ongoing phase II trials of its RNA-loaded dendritic cell product in renal cell carcinoma and HIV as well as support the further pre-clinical development of its CD83 soluble protein for transplant rejection/autoimmune disorders

In a move I'd say has some elements of "perfect timing", Novocell CEO, Alan Lewis, announced he plans to leave the company after 3 years at the helm to head up the well-funded and well-connected JDRF. Alan positioned the company well and leaves it with a healthier cash balance than many in its position. Due to the nature of ESC work and the financial markets Novocell has an arduous road ahead of it but they are at the forefront and have the backing from some heavy hitter investors.

Sigma-Aldrich entered into a research collaboration with South Carolina's D-Finitive Cell Technologies, Inc. The collaboration is expected to support the development and commercial offering of 14 products over a two-year span with a planned launch of many of these products in 2009 expected to consist of serum-free media for bone marrow and umbilical cord stem cells, mesenchymal stem cells and neural stem cells; cytokine cocktails for stem cell expansion and differentiation; novel formulations for cyropreservation of stem cells; and specialized products to conduct clonogenic assays of the various stem cells. Paul Price, the man behind the science at D-Finitive, is a key component to the deal.

James Thomson's Cellular Dynamics International- focused initially on creating cells for pharma toxicity testing - merged with its two sister companies, Stem Cell Products Inc. and iPS Cells Inc. and raised $18 million (link).

t2cure acquired a patent family in in vitro potency testing patents for testing of stem cells for cardiovascular applications which it intends to use in its phase III trial starting next year.

Cytori announced it is strengthens it European Union sales, training and service operations with key hirings and expansions. The company is introducing its Celution^® 800 System in Europe into the reconstructive surgery market. The Celution® Technology has been developed as a bedside device to enable real-time, adult stem and regenerative cell processing. The technology automates and standardizes the separation and concentration of a patient’s own (autologous) adult stem and regenerative cells from body fat (adipose) for real-time redelivery to the same patient - at the moment primarily patients recovering from the effects of breast cancer treatment.

Something's up at Stem Cell Sciences. Last week they announced they had signed a Master Service Agreement of up to five years with Pfizer Limited, the UK operating unit of the global research-based pharmaceutical company Pfizer, Inc. (NYSE: PFE - News). Under the terms of the agreement, SCS will provide research services, cell lines, media and reagents to support Pfizer's R&D efforts in the field. It is no secret the company has been busily reinventing itself and signing of a major deal with a pharmaceutical has been one of their stated goals since they did a major re-org of the company. Nevertheless, on the heals of the deal the company announced that they requested a temporary suspension in the trading of its shares ahead of what it described as a review of its financial position and strategic options. It will be curious to see what transpires.

As Jon Rowley pointed out, last week I missed Aastrom's announced treatment of the first patient in its U.S. Phase II trial of their Cardiac Repair Cells (CRCs) in the treatment of dilated cardiomyopathy (DCM).

That's just the way I saw cell therapy this week...

Cell Therapy HiLites 2008-11-14

Here's what caught my attention this week:

Celgene received FDA clearance to proceed with its placenta-derived stem cell clinical ttudy - a phase I, multi-center trial for moderate-to-severe Crohn's disease.

MiscroIslet filed for Chapter 11 bankruptcy protection but expects to restructure as a private company, continue operations, and file its first IND by year's end for an encapsulated porcine-islet product to treat diabetes.

Celladon released promising phase I results for the first gene therapy trial for advanced heart failure.

Cytori is starts to sell some of its StemSource® cell banking systems for collecting, processing, and storing adipose-derived cells. The company received its first order from Asian distributor Green Hospital Supply. The cell bank is to be set up in Japan. Despite all the continued skepticism about the value of cell banking to the donor-potential-patient, cell banking businesses are popping up prolifically around the world on the promise of short-term revenue to fund long-term R&D while providing a service some believe to be of irreplaceable value.

Although technically not a company-related cell therapy story, one of the more interesting developments this week was the announcement out of Charite in Berlin that they have a patient who is AIDS-free following a unique stem cell transplant. The patient developed leukemia which the docs were going to treat with a stem cell transplant. But rather than do the routine transplant by finding a match and treating just his leukemia they dared to be a little different. They went looking for a donor that matched and also had a CCR5-gene mutation (a naturally-occurring mutation which makes life difficult for the HIV virus according to some studies). The Berlin team found 80 compatible bone marrow donors for their patient, an unusually high sum, two of whom had the CCR5-Gene mutation. One of these they used with surprising and heartening results. What I like about this story almost as much as the happy ending and exciting discovery is how the doctors are trying to control the hype around this single-patient data and early results. It's not likely that this kind of transplant is a future treatmtent (for reasons related to supply, demand, and other commercial realities) but perhaps there is a kernal of a cell therapy product here somewhere that someone as innovative as these doctors will develop in time.

Ok I'm late on the draw here but it just came to my attention that in August NovaRx initiated a pivotal phase III in lung cancer patients. Watch on this blog in the coming days for more on the perception-vs-reality gap related to the number of industry-sponsored cell and gene therapy trials currently active worldwide.

Introgen may disappear while on the brink of success. Despite have an MAA being reviewed in the EU for their gene therapy for head and neck cancer, their BLA submission for the same therapy was rejected by the FDA as incomplete (currently under appeal). The company is now "exploring options" after a troubled Q3.

While not for its cell therapy program, Athersys announced it had achieved a clinical development milestone in its Bristol-Myers Squibb alliance. The amount of the milestone payment has not yet been revealed but any revenue is good revenue to offset the cell therapy development burn.

Bucking recent trends, StemCells Inc. (STEM) announced it will raise $20M in a stock sale to select institutional investors. Good news for any company in these times. Even better news for the cell therapy sector!

Finally, in the most over-reported news of the day, Pfizer opens up a regenerative medicine shop. I agree this is big news. This is not a minor investment; it's not throwing some money at a portfolio of biotechs in hopes that something will stick; it's not using stem cells as tools for drug testing or discovery. This is evidence of a belief by those in the halls of some of the tallest towers in life sciences, that cell therapies are going to change the way we treat people. Here are a couple quotes:

“Pfizer Regenerative Medicine represents a great opportunity to focus world-class research in a field that holds considerable promise for biomedical science and for the treatment of many debilitating conditions such as diabetes and neurodegenerative disorders.” said Rod MacKenzie, PhD, head of Worldwide Research at Pfizer.

The unit will be led by Chief Scientific Officer, Ruth McKernan, PhD, who said “I’m very excited to lead this new research unit. While there is still a lot to understand about how stem cells can be used therapeutically, we believe it is one of the most promising areas of scientific research.”

Ok, one more. Corey Goodman, PhD, President of Pfizer’s Biotherapeutics and Bioinnovation Center, said, “The formation of this new unit represents another key step forward in Pfizer’s commitment to be at the forefront of new approaches in biotherapeutics and bioinnovation and to expand our research efforts and expertise into emerging areas of biomedical science, like regenerative medicine, that have great potential for human health.”

Apparently the unit will operate independently (in the fashion of smaller biotechs) with about 70 researchers when fully staffed - in both Cambridge, UK and Cambridge, Mass - and work collaboratively with "leading academic, biotech and pharmaceutical partners around the world.


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

Drug Companies Ready for Cell Therapies?

Ok I won't title every blog in the form of a questions but this one seems a fitting follow-up to my last blog re: VCs.

Today Pfizer announced an investment in an early-stage (pre-clinical) cell therapy company. Forbes' commetary on the deal begins: "Big drug companies have largely stayed away from testing exotic stem-cell treatments. But now Pfizer is betting that a radical new adult stem-cell treatment may be able to stave off diabetes-induced retina damage, a leading cause of blindness. In an unusual deal, the big drug maker is funding the creation of a biotech company in San Diego called EyeCyte, which will develop stem-cell treatments for eye diseases." (click here for full Forbes article).

The press release states "The financing will fund the company into 2010 [the target date for phase I] and will be primarily used to drive product development of the company’s initial clinical target, diabetic retinopathy."

Friedlander and El-Kalay have a fascinating technology and it looks very promising in mouse models. It is, I believe, now being tested in primates. The approach is unique in that it encourages vascularization in a disease states often marked by overvascularization on the premise (borne out in very nice pre-clinical data) that using a highly purified progenitor cell population isolated from the patient’s own bone marrow using proprietary reagents and processes then injected to support healthy vascularization, prevents ineffective vascular proliferation.

In a conference this spring they also spoke of their efforts in looking at not only their scientific methodology but also already working on scale-up (bioreactor me-thinks?) technologies and closed production systems. This is uncharacteristically forward thinking (and admirable) for a company in early development stage.

There have been some encouraging signs recently regarding Pharma's involvement (or potential involvement) in the field.

As Langreth alludes in the Forbes article, J&J is indeed more involved than any other pharma peer. In fact, by my account they are by far the largest cell therapy company in the world if you add up their diverse projects around the globe. They have wisely diversified their investments to internal and external, therapuetic and tools, early and later-stage companies.

There were some, of late, who even presiently opined (or at least wondered aloud) about Pfizer's potential interest in cell therapy (see fellow-blogger J. Rowley's Dec 2007 post at http://tinyurl.com/3kj93m) given the creation of a new Bioinnovation Center "to focus on discovering and developing new medicines". Then in April Pfizer announced the creation of Pfizer Regenerative Medicine "a new research unit focused on stem cells and modulators of regenerative processes".

For the most part, pharma's interest in the sector to-date has been largely focused on the use of stem cells for discovery or testing. Understandable.

Pfizer's investment is modest: $3 million - with rights of first refusal to buy it outright. Hopefully with Pfizer on the board, the team finds a way to ensure that the fact EyeCyte can now leverage Pfizer's "prowess" is a positive influence on prudent development rather than a drag on momentum.

This is an encouraging notch on the bed post of cell therapy. Particularly autologous cell therapy at a time when many are - rather prematurely in my opinion - writing autologous therapies off in favor of allogeneic models. The venture might be a one-off and it might fail, but to me, this is just another small checkmark in the 'reasons-to-be-positive-about-cell-therapy-going-forward' column.

Stay tuned...