The Accuracy of Adipose Stem Cell Doses

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In August we published a blog post, "Are some cell counts too good to be true? Why some companies' product data may mislead", pointing people to a white paper released by INCELL Corporation.  That white paper appears now to have been pulled from their website (we are working to get a copy to make available again) but now they have published a paper providing more detailed data on aspects of their comparative cell count study.

The paper is introduced by the following abstract:

"Cell therapy products derived from adipose tissue have some unique processing issues with regard to obtaining accurate cell counts. This is because processing methods may not only show us the nucleated stromal vascular fraction (SVF) cells but also the micellular and microvesicle particles. This is true for both veterinary and human clinical products, and poses special concerns for in-clinic processing where the cell therapy dose is correlated with cell numbers and other QC data is not especially useful.

In this study, multiple cell counting methods were compared for SVF cell reparation that were derived from canine adipose tissue using commercially-available rocessing kits. The data clearly showed that many non-nucleated particles appear cell-like by size and shape, and can lead to counting errors with automated counters. In addition, certain reagents important to processing can have properties wherein the reagents alone (e.g., lecithin) may be counted as cells. The most accurate cell numbers were from hemocytometer-counting of cells stained with 4´,6-diamidino-2-phenylindole (DAPI) which shows the nuclei in concert with a viability stain such as trypan blue. The data clearly showed that care must be taken when counting cells used as a therapeutic dose."

This is an important issue particularly as it pertains to autologous cell-based treatments produced by point-of-care devices and/or kits.  I encourage you to read the paper.   

Morrison DG, Hunt DA, Garza I, Johnson RA, Moyer MP*. Counting and Processing Methods Impact Accuracy of Adipose Stem Cell Doses. BioProcess J, 2012; 11(4): 4-17.

* Dr. Moyer is CEO and Chief Science Officer for INCELL Corporation, 12734 Cimarron Path, San Antonio, Texas 78249 USA. www.incell.com

The ROI on pant-wearing and other social media tips

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With many things in life, there is a payoff for doing them.  Do the dishes and the kitchen is cleaner, your household is more functional, and hopefully one or more family members notice and appreciate you for it.

For other things, however,  the people around you have such high expectations you'll do them that you only lose points if you don't but gain very little if you do.  For you, this may be true of the dishes.  Certainly I've always maintained this is true for Valentine's Day.  Get flowers and you simply maintain the relationship's status quo; fail to do anything and you lose big points fast.  

Similarly, at some point certain things become so ubiquitous that they are expected as a baseline.  This is true of putting on your pants.

The global head of social media for Ford Motor Company, Scott Monty, once asked, "What's the ROI* of putting your pants on in the morning?".   The truth is that there is very little benefit to putting on your pants other than to avoid the significant cost of not doing so.

Certainly this is true now of having a website or an email address for your company.  Unlike a couple decades ago, no company gets kudos for having a website or email addresses but it would certainly raise eyebrows of criticism if your company failed to have them.

Arguably social media participation is not quite there yet but it is, I submit, fast approaching.  Someday in the not-too-distant future you will receive the cringe of shame if your company is not active in the leading social media platforms of the day.  Today - for companies - these are LinkedIn, Twitter, and Facebook.  This will be true irrespective of whether yours is a B2B or B2C company.

Recently I was invited to write an article for Future Medicine's special issue for the World Stem Cell Report.  I was asked to make the case for why and how participating in social media stood to benefit the scientists, companies, executives, employees, academics, activists, and other stakeholders in the cell therapy industry.  

The result is "Why the stem cell sector must engage with social media".  What I attempted to succinctly outline are the ways social media primarily benefit one's career and organization or company.

"I can tell you without the slightest hesitation of conviction – having experienced it myself and seen it repeated countless times – is that active and successful social media engagement translates into:

• Unparalleled learning: accessing more information relevant to your discipline, specialty and company than you otherwise will. 
• Enhanced profile: higher profile within your industry, profession, specialty and community. Social media is not the only way to build a profile but it can be very effective.
• Wider network: more touch points and meaningful relationships with people than you otherwise will accomplish by any other means combined."

The measurable impacts and benefits are real and certainly include:

• Traffic: "For companies, increased traffic equals increased opportunity to call readers/viewers to your intended action – interaction, citation, linking, investing, buying or engaging in some other action you solicit. For individual professionals, increased viewers translate into more chances for collaboration, citation, engagement, etc."
• Collaboration: "There is an intrinsic correlation between one’s profile and the opportunities one has for collaboration. For companies this means finding the right partnerships, joint ventures, strategic alliances, collaborators, employees, management and so on. For individual professionals, this means more and/or better quality invites to speak, write or collaborate in other ways. It also means finding quality grad students, faculty, employees and interns
• Revenue/Income: This is about translating a broader knowledge base and a wider network over which you have some level of influence (if only just that they are listening) into more money for your company, organization and yourself. For companies, this means finding the right partners, investors, customers and so on. For organizations this means finding the right donors, impressing the right grant reviewers and/or recruiting the right rain-maker faculty. For individual professionals this translates into promotions or job offers."

As I conclude my article I will conclude here:

"In order to create the kinds of perceptions and solicit the kinds of actions we want from the world around us, we must engage the world around us. The world around us is engaging online. 

For all kinds of selfish and selfless reasons you, your company or organization and your career will benefit from you engaging there too."

and this prediction:

"...in less than the blink it took for the commercial world to accept websites and email, it will seem similarly ridiculous for professionals, academics and companies to operate and succeed without actively using social media."

____________

If this topic is of interest to you, here are some great resources particularly focused on the value of social media to those in life sciences.

Canaday, M. Is Life Science Social Media Worth It Yet? Three Tenets Behind Its Relevance To Your Business. Comprendia. 6 December 2012. 

Bersenev A. Scientific blogging as a model for professional networking online. Cellular Therapy and Transplantation. 2010;2(7). 10.3205/ctt-2010-en-000084.01. 

Bersenev, A. Scientific blogging as a model for professional networking online. 4 August 2010. StemCellAssays.com 

Bersenev, A. Who’s Who in the Stem Cell Blogosophere.  27 June 2011. StemCellAssays.com 

Bishop, D.  How to bury your academic writing. Bishop’s Blog. 26 August 2012. 

Buckler, L. If You’re Breathing, You’re in PR. Cell Therapy Blog. 11 June 2010.  

Buckler, L. Don’t feel the pain of ignoring social media? Just wait a minute…. CellTherapyBlog.com 22 October 2008.    

Jewell, T. Survey: How our scientists use social media. AZHealthConnections.com. 12 February 2012. 

Knoepfer, P. Top ten tips for blogging for scientists. 2 August 2012. IPScell.com   

Shipman, M. Why Scientists Should Publicize Their Findings – for Purely Selfish Reasons. Scientific America. Blog. 18 June 2012. 
     
Shipman, M. A gentle introduction to Twitter for the apprehensive academic. Scientific America. Blog.  14 June 2011.  

Small, G. Time to Tweet. Nature 2011. 479 141 2 November 2011 

Wilcox, C. Social Media for Scientists Part 1: It’s Our Job. Scientific American Blog. 27 September 2011.  

Wilcox, C. Social Media for Scientists Part 2: You Do Have time. Scientific American Blog. 29 September 2011.  

Wilcox, C. Social Media for Scientists Part 3: Win-Win. Scientific American Blog. 10 October 2011.  

Wilcox, C. Guest Editorial: It’s time to e-Volve. Taking Responsibility for Science Communication in a Digital Age. Biol Bull. 22285-87. (April 2012)  

The Rules of Social Media.  Fast Company.  8 August 2012. 

A proposed 6-step platform for the cell therapy industry to consider in combating non-compliant cell therapy treatments

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Further to my recent post, "Six steps to fighting non-compliant cell therapy treatments. The stuff of grey shades, spades, ivory towers and (ahem) balls.", I have crafted a 6-point platform that I propose to submit (with potential edits based on preliminary feedback) to several of the leading  industry and professional organizations for their consideration including ARM, ISCT, ISSCR, FACT, AABB  ICMS, and perhaps, in due course, to patient groups, physician groups, disease-specific professional organizations (e.g, cardiology, oncology, neurology, cosmetic, etc).

I welcome comments and feedback. 

1. In addition to helping patients distinguish between compliant and non-compliant treatments (and providers) we must do more to help patients distinguish between non-compliant cell therapy treatments (and providers) which are more or less risky. 

2. Whatever we do in response to this issue should be done with an eye to being practical and helpful to patients in the real-life context of their decision about whether or not to buy a non-complaint cell therapy.

3. Our response to this issue should be based on a risk-based approach recognizing that not all non-compliance is created equal.  We should create a framework for risk-based analysis (both for us and our audiences) and focus initiatives around those which present the highest risk.

4. We recognize the problem of non-compliant cell therapies is not just a problem that exists in jurisdictions with little, no, or poor regulation but that is a growing problem even in the most highly regulated jurisdictions meaning the solution cannot be regulated it depends on education and enforcement.

5. We recognize regulatory agencies cannot enforce non-compliance on their own.  We as an industry need to complement their efforts through our own standards and enforcement.

6. Stakeholder groups should support the formation of a multi-organizational  initiative to, based on a risk-based assessment, spotlight the categories or signs of highest-risk offenders for use by patients and/or their physicians in identifying  whether or not treatments (and providers) they may be considering fall into the that category associated with the highest level of risk.

What do you think?

Six steps to fighting non-compliant cell therapy treatments. --- The stuff of grey shades, spades, ivory towers and (ahem) balls.

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Today an article entitled "Professors Critique Stem Cell Medical Tourism" appeared in the online version of The Harvard Crimson summarizing a recent panel discussion hosted in least in part by Harvard Law School assistant professor I. Glenn Cohen and University of Alberta law professor Timothy Caulfield.  The article concludes thusly:

The panelists emphasized that more accurate information should be provided to the public regarding stem cell treatments.

Certainly what Cohen and Caulfield concluded is true.  It has now been true for several years.  We keep saying it.  But are we listening to ourselves?  Are we doing anything meaningful to address this?  If so, is it enough?

Sadly (in my opinion, of course) the answer is 'not nearly enough'.*

For several years now, experts and organizations in the cell therapy sector have been saying that more must be done to educate and assist patients who are seeking stem cell or other cell-based treatments which do not comply with existing regulation and/or widely accepted medical or clinical research practices (hereafter called "non-compliant cell therapies").  

In my opinion, attempts to address this need by the sector's professional organizations, while important, have been unnecessarily feeble, not gone nearly far enough, and legitimately appear by many to be high-minded and pedantic. 

Almost all efforts to-date to address this issue by ISSCR, CIRM, ISCT and others including authors such as Caufield - as laudable and needed as they are - have been focused on helping distinguish between compliant and non-compliant treatments (and providers).  This is certainly much needed.  But what is left, I submit, is an even greater unmet need.

What almost all efforts to-date have failed to recognize or address is that where real help is needed is in helping patients distinguish between the many shades of grey among non-compliant treatments (and providers).

Emerging organizations like ICMS (now in partnership with AABB) have recognized and attempted to address this unmet need through a commitment to create some level of certification, accreditation or standardization of clinics participating in this business of selling non-compliant cell therapies.

While their intentions appear on-target as one meaningful way to address this unmet need and certainly their willingness to tackle this issue in a bold way is to be lauded, the ICMS is inexperienced and underfunded.  I remain hopeful that now through their new partnership with AABB they will be able to provide something that really addresses this unmet need but the jury remains out on whether they will succeed.

Anyone who has followed this blog and/or my threads on LinkedIn know I have been thinking about and discussing this issue for some time. In a desire to move to very concrete suggestions, I want to recommend the following 6 steps to my industry colleagues and professional organizations:

1.  50 shades of grey. Let's admit that this issue is not black-and-white but, as is almost always, involves a broad spectrum of grey in the middle.  

In addition to helping patients distinguish between compliant and non-compliant treatments (and providers) there are a lot of ways to help patients distinguish between non-compliant cell therapy  treatments (and providers) which are more or less risky.  

Let me use examples.  

On the one end of the non-compliant spectrum I would put forward a clinical like Okyanos Heart Institute which (as I understand it) intends to provide cell therapy treatments in the Bahamas to US patients using the Cytori system for cardiac conditions as soon as such treatments are perfectly legal and available to European patients but years before such treatments will be available in the US.  

Non-compliant?  Yes.  But certainly no evidence I'm aware of to support a belief that seeking treatment from them would be any more risky than travelling to Europe to receive the same treatment in a manner perfectly compliant with European regulations.

On the other end of the spectrum are the kinds of clinics highlighted recently by 60 minutes or which are the subject of ongoing lawsuits.

In between - in my opinion - are clinics like Stem Cell Institute and StemCellMD.

2.  Step out of the ivory tower.  Let's recognize that in certain circumstances patients are going to go pay for non-compliant cell therapies and we must do more to help these patients than simply shake our finger and tell them they mustn't.

For some, helping patients distinguish between the better and worst non-compliant clinics might involve a fair amount of nose-pinching but this is the equivalent of the methadone clinic for heroine addicts.  By supporting the better of two evils we are not endorsing it as 'good', we are simply recognizing it is better.

This is a recognition that we cannot just abandon people because they made (or are going to make) decisions with which we ultimately disapprove.   It is a recognition that sometimes the most righteous thing to do is not only to help people do what we would ideally want them to do but to help them do the best they can in their circumstances and on their terms - even terms with which we may ultimately disagree.

3.  A risk-based strategy.  Let's recognize that even the FDA triages their response to non-compliance and we would do well to do the same.  As a regulated industry we are perfectly comfortable with risk-based assessments and it should be applied here.  

Rather than treating all non-compliance as equally evil, let's apply some risk-based analysis to the situation and develop a strategy to root out the worst (highest-risk) offenders.  

4.  This is not just about tourism anymore - the problem has come home to roost. Let's recognize that this is no longer just a problem of patients leaving a regulated jurisdiction seeking a non-compliant treatment in a jurisdiction with no or more permissive regulation.  

Non-compliant treatments are growing rapidly even in the most highly regulated jurisdictions.  No where is this more true than in the United States.

5. Take responsibility.  Let's recognize that we cannot expect our regulatory enforcement agencies to do it all.  They are under-staffed and under-funded.  They - and the people we all serve - need our active participation in dealing with offenders and those risking patient safety.  

From a self-interested perspective, we owe it to our industry to help crack down on those who put the credibility and legitimacy of cell therapies at highest risk.

6.  Let's grow a pair and call a spade a spade.  If a non-compliant clinic is providing treatments that we believe represent a high-risk to patient safety and the industry's credibility, let's have the b*lls to call them on it.  They can't sue everyone.  

ISSCR backed down on their stem cell tourism initiative after being threatened by lawsuits. Who has stepped up in their absence?  Individual bloggers and authors like Paul Knoeplfer, Alexey Bresenev, Leigh Turner, and myself all who have been threatened with litigation several times for having the audacity to call certain non-compliant clinics out for what we deem - in our own risk-based analysis - to be the worst offenders.  

By way of example, several of my colleagues have recently committed to doing all they can do to call out David Steenblock and his non-compliant cell therapy treatments, many of which are provided at his clinic in California for a plethora of conditions.  In their opinion, many of his treatments represent some of worst examples of non-compliance in the United States right now.  There are many faces or fronts to his practice including www.davidsteenblock.com, www.stemcellmd.org, www.strokedoctor.com, www.davidsteenblock.net, etc.

If, as an industry, we act with more cohesion (collaboratively applying a risk-based assessment of non-compliant clinics) and speak with a more cohesive voice in terms of calling out those clinics and treatments which we conclude pose the greatest risk based on an objective set of criterion, this will present a multi-pronged, formidable and existential threat to clinics that they can't ignore or threaten away.

___

I will be taking these 6 recommendations to any organization who will listen.  I hope you will consider doing the same.

In the meantime - as always - I welcome your comments.

___

* This is my opinion not necessarily the opinion of any clients I represent or organizations I serve. Judge me - not them - accordingly.

Updated cell therapy index portfolio

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UPDATED AGAIN DECEMBER 1, 2012 BY ADDING NASDAQ:NWBO

This an update of a post originally released October 18.  What has changed is we've added four companies (shown below in red).

...

There are certainly analysts, traders, and brokers who cover the public segment of the cell therapy industry with much more expertise and experience than I -- among them is Henry W. McCusker of Scimitar Equity (@henryw09 on Twitter).

As part of our tracking of the sector's financial data and trends, we have created a portfolio of public cell therapy companies comprised of the 34 companies listed below (linked to their page on Google Finance).

I've been watching this portfolio since the beginning of the calendar year (January 2012) and have been commenting on its performance as against some of the major indices.  (Oct 8 post and Aug 10 post).  

In addition to these occasional reports I will occasionally report on Twitter (@celltherapyblog) on the stocks in this portfolio which are enjoying the largest gains/losses and which have the largest/smallest trading volumes.  From time-to-time I will aggregate this content into a blog post.     

Symbol         Name
ASTM        Aastrom Biosciences, Inc.
ACTC  Advanced Cell Technology, Inc.
ABH          Angel Biotechnology Holdings Plc
ATHX  Athersys, Inc.
AVMXY Avita Medical Ltd
BHRT  Bioheart, Inc.
BLFS BioLife Solutions, Inc.
BTX          BioTime, Inc.
CBAI         Cord Blood America Inc.
CNDO        Coronado Biosciences Inc.**
CCEL CRYO-CELL International, Inc.
CMXI Cytomedix, Inc.
CYTX Cytori Therapeutics Inc. (USA)
DNDN Dendreon Corporation
FCSC  Fibrocell Science Inc
IMUC  ImmunoCellular Therapeutics Ltd
ISCO International Stem Cell Corp
ISLT          Islet Sciences Inc
LVCLY       Living Cell Technologies **
MEDS Medistem Inc.
MSB          Mesoblast limited
MLM          Molecular Medicine SpA **
NBS          Neostem Inc.
CUR          Neuralstem, Inc.
NLNK  NewLink Genetics Corp
NWBO       Northwest Biotherapeutics, Inc.
OPXA  Opexa Therapeutics Inc.
OSIR Osiris Therapeutics, Inc.
PSTI          Pluristem Therapeutics Inc.
RENE ReNeuron Group Plc
REPCF       RepliCel Life Sciences Inc. **
STEM  StemCells, Inc.
TNGN Tengion, Inc.
KOOL ThermoGenesis Corp.
TIG           Tigenix NV

** added after original index portfolio was created October 18

Cell Therapy Industry Group Welcomes its 4,000th member

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I'm pleased to point out that today the LinkedIn Cell Therapy Industry Group welcomed its 4,000th member today. 

The Cell Therapy Industry group was created to serve as a network of those in the cell therapy industry. The group acts as a vehicle for referrals, networking, information, and facilitating collaboration.  The group's focus is on the activities of companies in and serving the space.

The group began in July 2008. It took 2.5 years to reach the first 1000 members, 9 mos to reach 2,0000, 6 months to reach 3,000, and 6 months to meet today's 4,000 member mark. 

As is typical, there is a very high percentage of passive participants but the group benefits from an avid group of participants who post, share, exchange, and debate on a range of topics ranging from regulatory, clinical, commercial, scientific, manufacturing, financial, and other topics of interest to the group.

As the group has grown I've noted two trends pertaining to the composition of the membership:  (a) having tapped out the c-level suite, growth is increasingly coming from down the hierarchy of the corporate food chain and including those in the operational trenches, and (b) a much higher ratio of new members of late is from outside the US, presumably as LinkedIn increasingly penetrates OUS markets.

We strive hard to maintain the quality of the participation by screening each applicant, deleting off-topic posts, moving promotional posts to the "promotions" tab" and encouraging a balance of news-sharing with useful discussion threads.

I'm proud to say the group has become a vibrant and valuable part of the sector due to the hard work and contributions of all involved.    

As these kind of virtual networks become exponentially larger and provide different value than the professional societies representing the sector, I will be fascinated to watch if and how this affects how sectors like our interact and how this will impact the traditional value proposition of member-based professional societies.

If you are not a member of the LinkedIn Cell Therapy Industry Group, check it out.

--Lee

GEN's "Cellular Therapy Wave Finally Cresting". An overview and data set.

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We first provided a listing (with very few details) of industry-sponsored late-stage (pivotal, phase 3 and 2/3) cell therapy clinical trials on this blog late last year (see the posting here).

We are now pleased to we have worked with Genetic Engineering and Biotechnology News and Enal Razvi of Select Biosciences to provide an updated (as of June 2012) and more detailed listing of industry-sponsored late-stage (pivotal, phase 3 and 2/3) cell therapy clinical trials (excluding cell-based immunotherapies which we intend to cover in a follow-up article).

A link to the listing can be found in an article published today entitled "Cellular Therapy Wave Finally Cresting" found in the November 1, 2012 issue of GEN.  

While not my favorite title, the article is a brief - but we hope useful - overview of the sector and its pipeline.  It also provides a snapshot of the cell therapy products already in commercial distribution. 

Some will quibble about the numbers. Certainly others have published larger revenue numbers, for instance, but in our view these have almost always included revenue from cord blood banking which we have excluded.

We encourage you to read the article but for convenience here is a direct link to the spreadsheet.  Of course it's already out-dated but we'll do an update again soon here on this blog.

Hope this is useful.

--Lee

[post-publication clarification]: Regarding the last sentence of the article, this should read:


"No cell therapy products approved 2002-8 vs 12 cell therapy products approved 2009-12."

2009-12 saw 9 regulatory approvals of industry-backed products : 

• ChondroCelect from TiGenix (EU),
• Provenge from Dendreon (US), 
• laViv from Fibrocell Sciences (US), 
• GINTUIT from Organogenesis (US), 
• HeartcelliGram-AMI from Pharmicell (S. Korea), 
• Cupistem from Anterogen (S. Korea), 
• Cartistem from Medipost (S. Korea),
• Prochymal from Osiris (Canada) and
• Prochymal from Osiris (NZ). 

This year also saw 3 regulatory (FDA) approval of two products from non-profits:

• HemaCord from New York Blood Center (US), 
• HPC, Cord Blood* from Clinimmune Labs, University of Colorado Cord Blood Bank (US)
• DUCORD from Duke University

* please also note the correction of "HPC, Cord Blood" which is the correct product name incorrectly stated as "Clinimmune" in the article.

Cell Therapy Industry Financing - Interim Update

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We've sent out a couple tweets from @celltherapyblog this week that we have now tracked over $1 billion having been brought in by companies in the cell therapy and cell-based regenerative medicine space this year to-date.  

We promise to post a breakdown of this stat updating our most recent post on the subject back in July but we want to wait until the month ends and we see a number of pending financings close.

We're closing the week with a Fibrocell Sciences ($FCSC) PIPE that was supposed to close Oct 11, an Immunocellular Therapeutics ($IMUC) secondary offering that supposed to close Oct 23, and an Athersys ($ATHX) secondary offering that aims to close by Halloween.

Watch for more details the first full week of November.

My cell therapy index portfolio

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So there are certainly analysts, traders, and brokers who cover the public segment of the cell therapy industry with much more expertise and experience than I. Certainly among the top of this crop is Henry W. McCusker of Scimitar Equity (@henryw09 on Twitter) who is preparing to launch a major new online initiative that I'm very excited about covering the entire regenerative medicine sector focused primarily on the public companies in the sector.

I tend to focus more attention on the activity of private companies in the sector that tend to get a lot less spotlight but as you know I have created a portfolio of public cell therapy companies comprised of the 30 companies listed below (linked to their page on Google Finance).

I've been watching this portfolio since the beginning of the calendar year (January 2012) and have been commenting on its performance as against some of the major indices.  (Oct 8 post and August 10 post).  

In addition to these occasional reports I will occasionally report on Twitter (@celltherapyblog) on the stocks in this portfolio which are enjoying the largest gains/losses and which have the largest/smallest trading volumes.  From time-to-time I will aggregate this content into a blog post.  

Symbol	Name
ASTM	Aastrom Biosciences, Inc.
ACTC	Advanced Cell Technology, Inc.
ABH	Angel Biotechnology Holdings Plc
ATHX	Athersys, Inc.
AVMXY	Avita Medical Ltd
BHRT	Bioheart, Inc.
BLFS	BioLife Solutions, Inc.
BTX	BioTime, Inc.
CBAI	Cord Blood America Inc.
CCEL	CRYO-CELL International, Inc.
CMXI	Cytomedix, Inc.
CYTX	Cytori Therapeutics Inc. (USA)
DNDN	Dendreon Corporation
FCSC	Fibrocell Science Inc
IMUC	ImmunoCellular Therapeutics Ltd
ISCO	International Stem Cell Corp
ISLT	Islet Sciences Inc
MEDS	Medistem Inc.
MSB	Mesoblast limited
NBS	Neostem Inc.
CUR	Neuralstem, Inc.
NLNK	NewLink Genetics Corp
OPXA	Opexa Therapeutics Inc.
OSIR	Osiris Therapeutics, Inc.
PSTI	Pluristem Therapeutics Inc.
RENE	ReNeuron Group Plc
STEM	StemCells, Inc.
TNGN	Tengion, Inc.
KOOL	ThermoGenesis Corp.
TIG	Tigenix NV

CIRM addresses some tough questions. Is it all just glass towers and basic research?

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At an industry conference recently I heard several new grumbles from companies about CIRM's alleged heavy bias toward funding basic, pre-clinical, embryonic stem cell-focused, academic-based research over clinical-stage, adult stem cell-focused, industry-sponsored product trials, testing, and development.

I myself have shared some concern that for an agency with a key goal of bringing new medicines to the next generation, having less than a handful of projects at the clinical stage this far into its mandate and budget was falling short well of its timeline.

I'll also admit to occasionally harboring a similar sentiment to that of former Intel CEO, Andy Grove, who is, of late, a grumpy critic of the slow pace of life science research when he said of CIRM in a great piece by Jeffrey O'Brien in Fortune Magazine, "CIRM? "There are gleaming fucking buildings everywhere. That wasn't necessary." (The great stem cell dilemma. Fortune. Sept 28, 2012)  

So...I decided to try to hit these concerns and criticisms head on with my friends at the California Institute for Regenerative Medicine (CIRM).  

What follows is an online interview CellTherapyBlog.com (CTB) conducted with the California Institute for Regenerative Medicine (CIRM) the week of October 15, 2012.  In the interview that follows, we were particularly interested in addressing the degree to which CIRM is focused - moving forward - on funding clinical-stage research, industry-sponsored trials, and clinical/commercial-focused product development.  

CTB: Would you please remind us of CIRM’s mandate?

CIRM: “To support and advance stem cell research and regenerative medicine under the highest ethical and medical standards for the discovery and development of cures, therapies, diagnostics and research technologies to relieve human suffering from chronic disease and injury.”

CTB: What percentage of grants or grant money distributed to-date has gone to companies?

CIRM: For-profit entities have been and currently are eligible for CIRM funding covering stages of research which range from basic biology programs (in which industry has shown little interest) through Phase II clinical trials. Of these programs, 13% have been awarded to companies thus far. Having built 12 state of the art stem cell facilities and having seeded  the field with training and other types of grants of similar purpose, CIRM is now focusing on funding translational and clinical programs.  

This is where companies' primary interests are and we expect greater company participation in our translation and clinical Request for Application. The translation and clinical awards programs provide for much larger awards as compared to the basic research and the overall amount of later stage funding is significantly larger than the earlier basic research awards. The number of awards made in the translational and clinical development funding rounds is much less than in the basic science area. 

CIRM’s Strategic Partnership Funding Program is a cornerstone of our efforts to fund industry.   We expect to make awards through this program approximately every six months to assist companies whose financing demands is frequently at shorter intervals than academic institutions. These awards will be made following a robust peer review process ensuring that awards are made to projects that are based on sound scientific data and have a reasonable chance of success.

CTB: How many CIRM-funded projects will be in clinical trial this year?  How many anticipated to be in 2013?

CIRM: Four clinical trials that were fostered by CIRM funds are already in clinical trials for cancer and blood disorders. We expect one or more CIRM-funded projects to join that list in the next year. This includes projects that are in clinical trial already for which we have funded and are funding the follow on studies.

CTB: Is CIRM actively seeking applications for clinical-stage projects? from companies?

CIRM: Yes, we have recently held the first round of applications for our Strategic Partnership Awards that are designed specifically to attract applications from industry and include significant leveraged funding from multinational biopharmaceutical companies and/or venture capital. The first of these awards will be announced at an upcoming meeting of our governing board, the Independent Citizens Oversight Committee. Industry also accesses CIRM funding through the Disease Team awards, which include teams comprised of both academic researchers and industry as partners, consultants and advisors. 

CTB: In its funding to-date more CIRM funding has gone to pre-clinical over clinical science, embryonic over adult stem cell research, and infrastructure over labor.  Is that a fair assessment?

CIRM: No. We have awarded more basic research grants in numbers, but those grants are much smaller in dollars than those in our translational portfolio. That translational portfolio includes 75 projects that have been awarded nearly $600 million, well over half of the research dollars committed.

When CIRM funding was initiated in late 2006, there was a need to build intellectual and facility capacity because doubts about support from federal sources had limited the entry of scientists into the field and there was a need for “safe harbor facilities. “ Research into stem cells was also at an early stage and so it made sense for us to focus on the discovery phase of basic biology and pre-clinical work to enable more effective utilization of the potential that was evident.

Increasingly however we are moving towards clinical science, to enable a proper assessment of the value of cell therapies and related approaches for advancement of human medicine.

Our focus has always included all stem and progenitor cells. Pluripotential stem cells are immortal and develop into all cells of the body, so the potential is large and the available funding outside CIRM has been modest. We have concentrated on human rather than animal model cells because this is where the need has been greatest. Our goal is to fund transformational research with the highest potential benefit to patients, regardless of the stem cell type they utilize.

As for infrastructure, we spent $271 million in major facilities grants to help create new, state-of-the-art safe harbor research facilities in California which are essential for  delivering  the goals of CIRM. That investment was used to leverage almost $900 million in additional funds from private donors and institutions to help pay for those facilities. Each facility  attracted new researchers to the state,  employed local construction workers  and created expanded research facilities that will now be able to offer long-term employment for the high tech innovators in stem cell research, transformative new medicines  for intractable disease and deliver economic benefit for Californians.

CTB: Given the juxtaposition of the relative dearth of CIRM-funded clinical projects to-date and the mandate to support bringing therapies to the clinic, in the last half of its mandate does CIRM intend to emphasize funding of more clinical projects? 

CIRM: Yes, our focus in our new Strategic Plan does just that, emphasizing the increased focus on translation and clinical trials. As described above, we are investing strongly in this sector. But we firmly believe that advancement in medicine is dependent on the science that underpins the medical strategies. We will also  continue to support high quality basic science that can transform medical opportunities.  

CTB:  If so, do you anticipate more of those will involve the use of adult cells over embryonic just by virtue of the fact more of these are closer to or already in clinical testing?

CIRM: We are required by our statute to fund in those areas that are under-invested. Otherwise we are agnostic to cell type. We expect a mixture of embryonic (induced pluripotent stem cells as well when they are ready for clinical studies), fetal, adult, cancer stem and progenitor cells, as well as small molecules, biologics and other approaches, evolving from stem cell assays and research. We are most concerned with the ability to produce results for patients.

CTB: I understand CIRM has made efforts over the past couple year to ease the burden or restrictions on companies applying for funds, is that true? 

Yes, we have appointed a Vice President with business development responsibilities and are further strengthening this capacity with key staff. We are actively working with industry to develop sustainable partnerships in research, we hold webinars and face to face meetings with the FDA to better equip industry with the tools that can aid in their investigational new drug (IND) submissions . We also assist industry to better understand what they need to do to successfully apply for CIRM funding.

We have also made changes to our intellectual property regulations and loan regulations to make it even more attractive for companies  to partner with us in research.

CTB:  I have heard it said that CIRM is not interested in funding late-stage trials.  Is that outside CIRM’s mandate or is it simply a matter of not having enough money to fund a late-stage trial?

Our focus has been in moving promising research through the "Valley of Death" phase, from the lab through Phase 1 and 2 clinical trials. We are working with major industry and financial institutions to inform them of our developing portfolio with the belief that they will be interested in taking many of these products to the market place. We are probably unable to afford to do these late stage clinical trials alone and feel it is likely that commercial interests will provide the follow on funding. 

CTB: If CIRM’s $20M could be matched with another $20M to fund a late-stage trial, would that be appropriate and feasible to entertain?

CIRM: We are always interested in proposals that will enhance our mission. While this hypothetical has not been put to us we would have to assess the proposal on its merits and our available finances. 

CTB: For clinical-stage companies outside California, what legitimate ties to California can be put in place to make one eligible for CIRM funding?  Is a company required to have a Californian entity or is it enough to have collaborations with a Californian entity or key service providers located within the state such as a California-based manufacturer or clinical sites in California?  What about having some staff in California?  Other ways?

CIRM:  In our RFA’s we have provided guidance as to what entities qualify for CIRM funding.  Future requirments  are presently under review by our General Counsel. Certainly, companies will need to show genuine steps at the time of application  towards relocation of a significant component of their research activities to California in addition to establishing a California operation with California employees. CIRM funding would be largely limited to in-state  activities.

My synopsis:  

I'm willing to reserve judging CIRM's overall track record of funding of clinical-stage and industry-sponsored research based on what it has done to-date.

My assessment of CIRM's contributions to clinical-stage science and product development will be heavily weighted on what it does from this point forward.

There is a certain rationale at play here that says they had to spend the first part of the mandate building the research infrastructure and scientific underpinnings required to move successful clinical and product development forward in the last half of its mandate. It may not be a rationale you whole-heartedly endorse but it is credible and I, for one, and willing to give CIRM the benefit of the doubt on this one. 

Having said that, my expectations for CIRM in the latter part of its mandate are very high with respect to how much they are going to dedicate to clinical-stage, industry-sponsored research.  

However, CIRM cannot do this in a vacuum.  What is required is for companies to do what they can to work with CIRM.  Don't give up on them based on their past record or your past experience.  Let's work with CIRM to help them focus their resources on moving some meaningful clinical milestones forward.

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I hope this interview helps clarify for readers just how CIRM views its ongoing and future participation in clinical-stage and industry-sponsored regenerative medicine research, testing, and development.

I would be happy to entertain and channel further questions anyone might have about CIRM (excluding those pertaining to specific applications or projects).