Cell Therapy Industry HiLites 2009-01-16

Ok, seriously, this week's HiLites blog almost killed me. Hope you find it useful. This was the week for cell therapy I thought last week would be. I'm going to try and recover now...



Dendreon's (NASDAQ: DNDN) Mitch Gold announced at this week's JP Morgan conference (click here to hear the presentation) that the IMPACT study of 500 men with terminal prostate cancer will offer a final answer by April on whether its experimental immune-boosting drug helps patients live longer. When the company went to the FDA with its BLA for PROVENGE in late 2006 and - despite the advisory committee's 13-4 vote recommending approval (March 2007) - the FDA voted against approving it at that point, it was this trial the FDA said they would prefer to see the data from before deciding. There is, as always, a much longer checkered history of ever-changing FDA reviewers, missed clinical endpoints, retrospective data analysis to find a patient subset for which the therapy worked, etc, etc all of which are partial drivers I'm sure for deciding to wait for the data from this second phase III study --- but it all comes down to this. In a mid-point preliminary review of the data, the endpoints were not met - but they were almost met. Mitch Gold is, of course, confident. As was the case in early 2007 there will be much speculation and the stock will be traded wildly and the cell therapy industry will wait with bated breath - though perhaps not quite as bated as 2 years ago when it seemed more rode on the decision than it does now.

The company has built its own manufacturing facility on (perhaps in due course only for) the US East Coast (New Jersey). They still own the worldwide rights to market the drug. They intend to go to the US market with a ~120-person sales force and plan to seek a commercialization partner for marketing outside the U.S.

In other late-stage cell therapy news, Osiris had a successful pre-BLA meeting with the FDA in which they reportedly reached agreement on the timing and content of their anticipated BLA submission. This will be the first US marketing application for a stem cell product making it much-anticipated, globally monitored, and precedent-setting. The entire industry has been waiting for this moment for several years (the last cell therapy approved being 10 years ago!) and will be watching this in much the same way as we were all watching Dendreon's BLA submission a couple year's ago.

Reported key results of the pre-BLA meeting were:
• FDA agreed with the proposed content and structure of the BLA for Prochymal for the treatment of GvHD.
• The primary endpoint of the Phase III trial that will be reviewed by FDA for approval was confirmed to be GvHD Complete Response (CR). A CR is complete remission of the disease.
• FDA indicated that the statistical analysis plan was appropriate.
• The overall safety database (Integrated Summary of Safety) of Prochymal is sufficient in scope for the indication. No additional clinical data beyond what was presented is anticipated to be necessary for the BLA.
• Agreement was reached on BLA requirements for Chemistry, Manufacturing and Controls (CMC) data.
• The FDA concurred with the proposed product stability and process validation plan for submission and provided guidance on how to present the data for ease of review.
• Agreement was reached on the timing and content of the BLA in rolling submission format. The rolling submission is an FDA provision available to drug candidates that have received Fast Track designation, which allows for completed sections of a BLA to be submitted on an ongoing basis. It can facilitate the process by allowing FDA to complete review of sections as soon as they are available. It is anticipated that the nonclinical sections, such as toxicology, will be the first submitted for review.
• The BLA will be in the electronic Common Technical Document (eCTD) format. The eCTD format facilitates the review of the BLA and allows parallel submission of the dossier in other territories.
• At the time of submission, Osiris will also submit the request for Priority Review of the Prochymal BLA. Investigational drugs with Fast Track designation are eligible for consideration for Priority Review, which provides for an accelerated six month application review by FDA

In other news not to be overshadowed by the news about the pre-BLA meeting, Osiris received FDA clearance to broaden the Prochymal Expanded Access Program (EAP) to patients of all ages suffering from life-threatening GvHD. In May of 2008, FDA approved the first Prochymal EAP for the treatment of pediatric GvHD patients. Congress and the FDA created the expanded access program to facilitate the availability of promising new drugs to desperately ill patients before general marketing begins.

If you're interested, click here for an interview of Osiris CEO, Randal Mills, done by PharmaExec.com this week.

Invitrogen launched a xenogeneic-free media for human embryonic stem cell culture.

After now at least 4 years of GE Healthcare's campaign to build a 9-figure cell therapy division, a rocky relationship with Thermogenesis, and the splashy acquisition of Wave Biotech, GE has made another entree into the sector with its announcement of a partnership with Cytori (NASDAQ: CYTX) to commercialize Cytori’s Celution^® System in select European countries - exclusive for 18 mos in select countries. While GE is admittedly not lighting any fires with the pace in which they are building this division it is presumably (hopefully) strategic, synergistic, supportive of its overall business and...please let this be true...something Jeff Immelt will continue to wholeheartedly support despite the perpetual and perpetual re-orgs within the company.

Celprogen claims to have successfully de-differentiated adult somatic cells (primary skin fibroblast, keratinocytes, cardiac, liver and neuronal cells) to their embryonic pluripotent cells (iPCs) using a proprietary non-viral method involving their de-differentation media and matrix system. The iPCs were then reportedly differentiated into cardiac, neuronal and hepatic tissue with Celprogen’s Stem Cell Differentiation system.

The PerkinElmer ViaCord Research Institute and M. D. Anderson Cancer Center have agreed to extend collaboration on a study of cord blood stem expansion systems in adult transplantation. The study seeks to discover methods of treating more adults using cord blood stem cells using 'co-culture' expansion technology. Based on the results of this trial, ViaCord, PerkinElmer's cord blood banking business, and M.D. Anderson will determine the feasibility of using Unrestricted Somatic Stem Cells (USSCs) derived from cord blood in the co-culture of cord blood units for transplantation. USSCs, proprietary to ViaCord (patent pending #09/985,335), are a type of stem cell found in umbilical cord blood, which have the ability to differentiate into many cell types, including endothelial cells, fat, bone, cartilage and neuronal cells.

ERYtech Pharma, French biotech company developing a pipeline of products involving the encapsulation of therapeutic molecules inside red blood cells for a variety of orphan indications, has signed an agreement with Penn Jersey Region of American Red Cross for the "GMP" clinical batches production of ERYtech Pharma’s products in the United States.

I'll seque momentarily to the regretably inevitable 'bad' news ...

On the verge of filing a BLA, Isolagen (Amex: ILE) is forced to downsize its operations to minimize burn-rate and postpone bankruptcy while exploring its 'options'. On November 6, 2008, the Company disclosed in an SEC Form 10-Q that there existed substantial doubt about its ability to continue as a going concern, and that its ability to continue as a going concern was contingent, among other things, upon its ability to secure additional adequate financing or capital prior to January 15, 2009 under its current operating plan and condition. The company announced it was pursuing dual paths, including pursuing potential financing alternatives as well as continuing potential strategic partnership discussion. As of this week neither event has happened according to an SEC filing.

The Company has now deviated from its normal operating plan and is focusing its remaining cash resources on specific clinical programs, namely efforts to complete its Biologics License Application related to the Company’s Phase III Nasolabial Fold study, and continuing its IT-R-008 Phase II/III Acne Scar trial. All other clinical programs have been suspended in order to preserve the Company’s remaining cash resources. The company believes it can survive for awhile but not sure how long. Its largest debt is a $90M liability which can be called by one of the noteholders as early as November.

Arbios Systems, Inc. (OTC: ABOS) has filed for chapter 11 bankruptcy protection while they continue to seek bids for the sale of the Company and/or its assets - namely the SEPET™ Liver Assist Device (a blood purification therapy designed for use with a standard blood dialysis system). The company shuttered its operation in August to focus "day-to-day operations exclusively on obtaining financing or consummating a strategic transaction'. In October the company sold all its rights and interest in its bioartificial liver system, HepatAssist, to HepaLife Technologies, Inc. (OTCBB: HPLF). This was really the cell therapy part of the company. The HepatAssist™ Cell-Based Liver Support System - a hollow fiber cartridge housing living porcine liver cells - purportedly functions as a bioartificial liver that not only detoxifies the blood, but, uniquely, provides whole liver function - intended to treat acute and acute-on-chronic liver failure patients.

This is a buyers market and the reality is many potential investors or purchasers are not motivated to buy a going concern for $x if they can scoop up the assets and/or business at a significant discount under distress. Regretable for those companies that have created and nurtured good technologies but allowed their business to fail; good news for those with cash; perhaps also good news - say some - for a much-needed reorg of an industry with a much more disciplined commercial focus.

Last month we talked a little about Bioheart (Nasdaq:BHRT) and their IPO less than a year ago raising just under $6 million. Now the stem cell company Bioheart has alerted the SEC that it missed a scheduled $180,000 loan payment and is seeking new money to keep the company going.

The Miami Herald reports that the Sunrise, FL-based developer has warned investors that it faces some tough choices including potential layoffs, bankruptcy and closing the business. But, reports Jim Carroll from Fierce Biotech reports, "the company's CEO, Howard Leonhardt, says the lender--BlueCrest Venture Finance Master Fund--has agreed to provide an extra 90 days for the company to make the payment. Bioheart, he adds, had to deal with an unexpected delay in receiving a $2.5 million loan and he insisted that the company is not in danger of closing."

According to Leonhardt, ''The last 24 months in a row we've paid on time and it was an unforeseen event. We're not thinking of bankruptcy at all; it's not even close to consideration -- maybe laying off employees.'' But all is not as serene as a pic of the debonair Leonhardt, accompanying the Herald story, would seem to suggest. A group of board directors and key executives have departed the company in the last two weeks, including CFO William Kline.

Nonetheless, there is reason to be optimistic despite the alarm bells. Bioheart - which is not just a one-trick cell therapy pony - recently announced the approval or release of four new products. In October, it launched in the United States and Europe a heart failure monitor that patients can use at home. Several major sales contracts are pending and the company has set a $20 million goal for 2009, Leonhardt said. It has also won FDA approval for the Bioheart Monebo CardioBelt, which heart patients wear around their waist, as well as commercial approval for two other technologies in Europe. Also, while I still have unanswered questions about who is supplying who with what, they also recently signed a cell supply agreement with Life Technologies to sell myoblast cell-based research products to life science researchers. By March, Leonhardt said, Bioheart should be on sound footing cash-wise and would try to fund operations solely with revenue and profits. Until then, however, ''we have to bring some more capital in now to bridge the gap,'' Leonhardt said.

On now to more optimistic fronts...

In a recent interview, CIRM President, Alan Trounson, said he (CIRM) is lobbying for the creation of an 'investment' fund - sponsored by government and health insurers - to drive commercialization of early regenerative medicines. He fears that without such a 'new paradigm', the lack of funding on the scale typically provided by the pharmaceutical industry, could well be a roadblock in regenerative medicines being brought to market. Trounson predicts within 10 years we'll have new drugs based on stem cell discoveries and clinical products being tested for spinal repair, retinal repair, cardiac function repair, multiple sclerosis, etc.

BioE recieved FDA 510(K) clearance for its cord blood processing system. PrepaCyte-CB is available immediately to public and private banks separating potentially therapeutic cells and stem cells from cord blood.

Pluristem Therapeutics (NasdaqCM: PSTI; DAX: PJT) filed an IND with the FDA to initiate a two-center Phase I clinical trial in the U.S. utilizing PLX-PAD - placental adherent stromal cells (ASCs) expanded in the Company's proprietary PluriX TM 3D bioreactor - for critical limb ischemia. The company filed a IMPD in Europe for a similar trial there.

The Swedish investment company Karolinska Development AB has made what it calls a "significant investment" in EvoStem Finland Oy - a company that develops stem cell and other tissue engineering based treatments for veterinary use (and intends to go human at some point). In 2007 EvoStem Finland Oy introduced to the Scandinavian market its first product TendoStem(R) - a stem cell based treatment service for tendon and ligament injuries in horses.

Kiadis Pharma has recently come out with a bunch of news (some of which I'm a little late reporting). Most recently they Dr. Maarten Egeler, MD PhD as Chief Medical Officer and in December they reported the appointment of Mark Skaletsky to its Supervisory Board and, most significantly, announced they have received two orphan drug designations for Reviroc™ from the FDA - one for diffuse large B-cell lymphoma and the other one for the treatment of follicular lymphoma. Reviroc™ is under development for the elimination of cancer cells from an autologous graft in bone marrow transplantations for end-stage blood cancer patients.

Skaletscky, for those of you who don't know him, is very well credentialed. He served as president and CEO of GelTex Pharmaceuticals, Inc. (acquired by Genzyme for more than $1 billion in December 2000), was chairman and CEO of Enzytech, Inc., and president and Chief Operating Officer of Biogen, Inc. He is also a former chairman of the board of directors of the Biotechnology Industry Organization (BIO). Currently he is chairman, CEO and president of Fenway Pharmaceuticals, Inc.

Let me digress momentarily with a little history and speculation...

In 2001, Theratechnologies (TSX:TH) reorganized its business activities through the transfer of its ex vivo photodynamic cell therapy program to its newly created subsidiary, Celmed BioSciences, the acquisition of NeuroGeneration and NeuroGenomics, two California corporations which were developing technologies for the treatment of neurodegenerative diseases, and investments totaling $60 million by Societe generale de financement du Quebec (SGF) and the Solidarity Fund QFL. Michel F. Levesque, founder of NeuroGeneration became Vice President, Medical Affairs with Celmed BioSciences.

In 2006 Kiadis B.V and Celmed BioSciences Inc. merged the two oncology-focused companies. At that time, CelMed Biosciences was a wholly-owned subsidiary of Theratechnoloies (another Montreal company). The new combined company was named Kiadis Pharma B.V. Investors include Alta Partners, LSP, and DFJ Esprit. At or around that time, Levesque took back NeurGeneration which he is now attempting to re-launch from his practice in Hollywood, CA.

Kiadis still describes itself as a "Dutch-Canadian enterprise" which is "endorsed by our investors, academic partners and a cross-Atlantic management team". There is much cross-pollination between Montreal and Amerstdam. For instance, Pierre Caudrelier, was until this week, CMO at Theratechnologies, was previously CMO at Kiadis Pharm, VP of Clinical Research at Celmed, and VP of Clinical Research and General Manager the the Canadian subsidiary of IDM (another company that had cell therapy products with US-EU connections). Research collaborations also exist with Italy, Germany and the US (including NIH's John Barrett).

Here comes the complete and utter speculation. On the one hand we have an unnamed fairly large multi-national company (not GE) looking for acquisitions in the cell therapy space. Links have been established with personnel at Theratechnologies - a company which I believe no longer has any cell-based therapy research. On the other hand, totally unrelated to this, I am led to believe that Kiadis is looking for a partner with money. Other than some personnel and history, there would not appear to be anything still linking Theratechnologies and Kiadis. However, just to make things a little curious Theratechnologies announced this week that Dr. Pierre Caudrelier was leaving his position as chief medical officer to pursue other career opportunities. Despite the complete lack of any evidence other than this tenuous string of bits and bytes, something tickles my senses here. I'm betting there is more to this puzzle than I have yet been able to put together (or am willing to say out loud at this point). Stay tuned.

On the regulatory front...

FDA CBER has announced their Cellular, Tissue and Gene Therapies Advisory Committee 2009 meeting schedule: May 14-15 and November 5-6

For those of you using genetically engineered pigs for to grow cells, tissues, or organs that can be transplanted into humans with a reduced risk of immune rejection, you will know the FDA this week issued its Final Guidance on Regulation of Genetically Engineered Animals. For the rest of you, I can't think of better night time reading...

The FDA issued a Draft Guidance for Industry entitled: "Current Good Tissue Practice (CGTP) and Additional Requirements for Manufacturers of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps)" [pdf version]. Although you can comment on any guidance at any time (see 21 CFR 10.115(g)(5)), to ensure that the agency considers your comment on this draft guidance before it begins work on the final version of the guidance, submit written or electronic comments on the draft guidance by April 16, 2009.

Let me mop up with a few final lighter entries.

Rurther to my blog on the subject back in October, BioTechniques just released interesting results on a survey of the extent to which scientists are using social media tools and which one for what. See more details in the comments section of my original blog post of social media use.

If you're planning to be at the Phacilitate Cell & Gene Therapy Forum in Washington, D.C. January 26-28 (and you should plan to be there if you have any interest in this field), here's a couple things to watch for:

- DCi Biotech consultant, Dawn Driscoll is moderating a lunchtime session on Tuesday the 27th hosted by Progenitor Cell Therapy in which yours truly, Robert Preti, and RTI Health Solutions, Eric Faulkner will be speaking. The session is entitled"Select Issues in Commercializing Cell Therapies" and will include a talk by Faulkner on positioning cell therapies for reimbursement.
For more details, click here.

- I will be there with the founders of BioBusiness.TV who will be there to capture some interviews from cell therapy industry executives for a cell therapy channel we are opening for the site.

- Anyone interested in potentially incorporating in vivo cell tracking/imaging in their cell therapy clinical trial, come find me.

Ok...one more thing just for kicks. For a chuckle and then a shake of the head in dismay check out the Niche blog on ESC-derivative facials! The hype is really getting out of control.

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That's it. That's all I've got for you. That, my friends, is how the cell therapy industry hit me me this week.

--Lee

p.s. Quick question: Do you mind/like this rather rambling format or should I get more organized somehow or another? Comment below...