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...

What's in a Name? The FDA's Got Yours.

At the ISCT-FDA Somatic Cell Therapy Symposium this Fall, there was much discussion about product nomenclature for cell therapies. It was a new subject for many in the audience.

CBER observed that several organizations in the sector are now laying the groundwork for setting standards in product nomenclature of HCT/Ps as a means of supporting and facilitating reimbursement, commerce, quality control (standards), labeling, etc. By asking that the session be included in the meeting, CBER wanted to ensure that such efforts were done in compliance with the product nomenclature framework that FDA already has in place.

Obviously this was top-of-mind also because at the time they were putting the finishing touches on a draft guidance for industry entitled "Contents of a Complete Submission for the Evaluation of Proprietary Names" which was just released.

For more background information, review Kim Benton's slides from the Somatic meeting. Darrin Weber also reviewed USP's efforts in putting together a product nomenclature monograph and Fran Rabe summarized ICCBA's efforts in applying the ISBT-128 labelling to human cells and tissue products. Click here for a link to these presentations (listed at the bottom of that page).

The guidance applies to proprietary name submissions for prescription drug products, including biologics, that are the subject of a new drug application (NDA), an abbreviated new drug application (ANDA), or a biologics license application (BLA), or that are currently the subject of an investigational new drug application (IND) in anticipation of submission in a marketing application.

The FDA does not perform premarket name review or labeling review of HCT/Ps regulated under PHSA 361 .

The draft guidance is open for comment for 60 days from the date it was published in the Federal Register.

Cell Therapy HiLites 2008-11-21

This is a week in which 2 of GEN's top 7 News of the Week stories were about regenerative medicine and they weren't even the two big financing events. Not bad.

Good news for Tissue Genesis Inc and their Commercialization Consortium partners Bioheart and VetStem. Effective immediately, the Tissue Genesis Cell Isolation System will be available to the European marketplace.

In a piece about biotech survival, Luke Timmerman, now of Xconomy.com, reports that according to an October report by Eun Yang, an analyst with Jeffries & Co., "about half of the 248 unprofitable biotechs that are publicly traded have less than a year’s worth of cash on hand".

Dr. Michael D. West announced an open letter to President-Elect Obama signed by 22 scientists and economists (including 19 Nobel laureates), urging the new Administration to make regenerative medicine, specifically, the cure of human disease, a national priority, similar in scope to the Kennedy Administration’s commitment to land a man on the moon within that decade.

Aldagen announced positive phase 1/2 results for ALD-301 (an autologous, bone marrow-derived stem cell population expressing high levels of ALDH) for critical limb ischemia.

The story everyone loved this week was the new trachea built from autologous stem cells and effectively transplanted in Spain. Chalk one up for more proof-of-principle but more consternation on the "business models" side of things. Researchers and surgeons from Britain, Italy and Spain collaborated to grow tissue from Ms Castillo’s own bone marrow stem cells, using them to fashion the new bronchus – a branch of the windpipe. Details of the transplant, performed by Paolo Macchiarini, at the Hospital Clinic of Barcelona, are published online in The Lancet and discussed in accompanying commentary. First a section of trachea was taken from a donor and stripped of cells that could cause an immune reaction, leaving a grey trunk of connective tissue. Stem cells were then taken from Ms Castillo’s bone marrow and grown in Professor Birchall’s laboratory to cover the 7cm graft. It was then “seeded” with the new cells using a process developed in Milan. Finally the trachea, covered in cartilage and lined with epithelial cells, was cut to shape and fitted. The researchers said that the surgery could help some patients in Britain but admitted that the procedure was too expensive to be widely available. They are seeking EU funding and commercial sponsors for trials to create and transplant a larynx, an operation that could be more cost-effective.

The two stories I loved the most this week were finance-related.

Last week Stem Cells Inc. announced its intention to raise $20M gross and this week it closed the deal netting $18.5 million from institutional investors.

Not to be outdone, Tengion raised $21 million in a second close of its Series C adding Safeguard Scientific to its heady roster of investors.

What money does exist for investing in cell therapies appears to be increasingly focused on a handful of companies that have demonstrated a somewhat mysterious capability to ease money from investors. Stem Cells, Inc and Tengion are two of the best along with MolMed in Italy which netted around $76M in an IPO earlier this year. Osiris has also done well on the public markets but also through the undying commitment of Peter Friedli and timely deal-making. Notable mention should also go to Aldagen (despite them having to recently pull a planned ~$80M IPO), Novocell, Geron, and Dendreon who all have done well in the past with investors.

This trend for capital congregation is nothing new. It certainly supports popular notions that either investors all think the same or they are lemming-like in their movements. It certainly does not bode well for the plethora of companies out there that are on the brink of burnout despite having seemingly strong management and data but do not seem to have that same type of investor-attracting charisma as the likes of Weissman/McGlynn, Nichtberger, Bordignon, Mills, Lewis, Okarma, or Gold.

At the end of the day, a company's success almost always comes down to its rainmaker. This is not a "if-you-build-it-they-will-come" type of industry. Great science, technical prowess, manufacturing experience, or even business acumen will not get companies over the threshold without that someone with that somewhat magic prowess to relieve investors of their money. Many cell therapy companies are now learning that lesson.

In the interim, from a mere objective point-of-view I could argue it's not a bad thing that investors focus precious resources on a few companies' products, get them approved, and get some fresh upticks in the "precedent" column for cell therapies and the new therapeutics and business models they represent. Like lawyers - and perhaps its because there are so many law degrees in the halls of VC firms - nothing makes them more comfortable than precendent.

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

How mature is the cell therapy industry? Do we know?

Survey
The week of November 17, 2008 I posed the following one-question survey:

How many phase III or pivotal industry-sponsored cell or gene therapy clinical trials do you believe are currently ongoing in the world?

to members of the following groups:

• those who follow me on Twitter (currently a group 43 individuals sufficiently interested in cell therapy to follow my postings);
• my connections on LinkedIn (a group of 188 professionals in or interested in the cell therapy sector);
  
• the 90 or so members of the LinkedIn Cell Therapy Industry Group;
• readers of this Blog; and
  
• the roughly 55 members of ISCT's cell therapy commercialization committee.
  

There was no control on multiple responses and no restriction on participation. Participants were forced to choose only one answer among responses ranging from 1-5 to 50+ in increments of 5 (e.g., 1-5, 5-10, etc).

Data, Assumptions, & Observations
There have been 18 responses to-date.

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

Based on these assumptions, the data leads to one simple, overarching observation:

There is significant divergence of perception (and perhaps misconception) about the maturity of the cell therapy industry even among those in and/or informed about the sector.

My database tells me there are 33 industry-sponsored cell or cell-mediated gene therapy trials currently underway around the world.

45% of survey participants answered fewer than 15 to the survey question; 33% indicated more than 45. In fact, only 1 participant (6%) do-date has chosen the category of 30-35.

Analysis
Admittedly this is an unscientific and informal survey. Furthermore there is likely some margin of error to account for different interpretations of what "industry-sponsored" means and/or what types of products should be included/excluded as "cell or gene therapies" since none of these terms were defined for participants.

Certainly in my day-to-day dialogue with people in the industry, the typical opinion is that there are but a handful of late-stage cell therapy trials (far fewer than what my data tells me actually exists). Having said that, when I asked a colleague in the industry yesterday to respond verbally to the survey question, they said "350" ( and then pulled back to say "maybe 200").

There is no doubt my data likely lacks a material number of industry-sponsored, phase III or pivotal gene therapy trials - given that the focus of my database is cell therapy and thus typically only includes cell-mediated gene therapies. This exposes a weakness in comparing the survey results to my data in that the survey related to "cell or gene therapy" while my data likely only reflects a small subset of gene therapy trials.

There is also without doubt more than 33 cell therapy or cell-mediated gene therapy clinical trials currently underway in the world with many of the indicia of a "late-stage" trial if one includes what is happening in markets where such trials or products are currently unregulated. I have not included these in my data because there is no mechanism for identifying whether such trials are, indeed, phase III or pivotal as there is no mechanism as yet in those markets for formal review or approval of these trials and/or products.

Nevertheless, what conclusions can/should be drawn?

• There is much divergence of perception on the maturity of the cell/gene therapy industry even amongst those in the sector.
• Even if my data is inaccurate, compared to whatever the real number is there is a significant % of industry professionals who are suffering from significant misconceptions about the true number of late-stage industry-sponsored trials in the sector.
  
• Good data on the state of the cell/gene therapy industry is not readily accessible.
• If those in the industry lack consensus on the state of the sector, it is no wonder investors and others outside the industry have mixed opinions on the matter.
• We need to do a much better job as a sector in gathering and communicating solid data on the commercial side of the cell/gene therapy industry.
  

For those interested in the data, here's how it looks:


Industry-Sponsored Cell or Gene Therapy Phase III or Pivotal Clincial Trials (Nov 2008) - DocStoc

Coming soon...a similar discussion on the number of cell therapy products currently commercially available around the world.

In the interim, if any of you have data relevant to this discussion, please share...

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.

one-question survey

I am trying to pull together some data on "perceptions" regarding the cell therapy industry and ask that you complete my one-question survey by clicking here: http://tinyurl.com/62brra

Thank a veteran today

We may not agree on everything...

We may not even agree on the need for war.
But we can agree that our world would not be what it is today without brave service men and women willing to fight oppression and protect freedoms.

Thank a veteran today.

Cell Therapy HiLites 2008-11-07

I'm not going to turn this blog into a news service by any means, particularly since I wouldn't want to compete with what I already created in Cell Therapy News - still the single best news source for this sector. I'm going to aim, however, to put out a brief weekly email highlighting what I believe to be some of the key content I noticed during the week (news or otherwise).

For what it's worth, here's what I noted this week.

Athersys, Progenitor Cell Therapy, NeuroNova, Stem Cell Sciences, and Amorcyte featured in GEN article on regenerative medicines. GEN Oct 15 2008 (Vol. 28, No. 18)

Onyvax publishes data supporting the notion that the intersection of biomarkers, personalized medicine, and cell therapy is just around the corner and it will turn medicine on its head. They believe they have identified a biomarker profile that could be predictive of response to cancer vaccines.

Science Direct's Top25 Hottest Articles for 2008 Q2 have a very high ratio stem cell-related publications.

It was a big week for BioLife Solutions with several new adoptions of their preservation and storage media as well as the filing of their second MasterFile with the FDA.

On the economic front, the Genzyme-Osiris deal (worth a potential $1.4B) was obviously great news for a sector so keen to see signs that investors aren't shunning the field but on the other hand is something of a confirmation that companies will have to get creative to survive what Burrill projects will be a lengthy dry-spell in terms of biotech investment.

Invitrogen & Applied Biosystems resurrect the Life Technologies brand as the new name for their merged entity.

Sartorius Stedim relieves us of the confusion of having two Wave Biotech's out there with single use bioreactor systems (SUBs) by purchasing the European Wave Biotech AG. (full story)

The FDA takes a new approach to the annual HCT/P Establishment Registration Updates. (link)

Finally, if you haven't checked out www.biobusiness.tv yet you really must. Jean-Loup Romet-Lemonne has created a valuable biotech business video content channel that promises to focus a great deal on cell-based therapies because of Jean-Loup's experience in and passion for cell therapies.

Until next week...