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Commercialization of Regenerative Medicine: Learning from Spin-Outs

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The meeting “Commercialization of Your Regenerative Medicine Research: Lessons from Spin Out Successes” was hosted by the Oxbridge Biotech Roundtable (OBR) (Oxford, UK) at the University of Oxford in February, 2013, and attracted a multi-stakeholder audience spanning academia and industry. 


The event featured case studies from Gregg Sando, CEO, Cell Medica (London, UK), John Sinden, CSO, Reneuron (Guilford, UK), and Paul Kemp, CEO and CSO, Intercytex (Manchester, UK). 


OBR is a student-led initiative with over 7000 members across eight different UK and US locations with a mission to foster a conversation about the healthcare and life sciences industry. 


Anna French and David A. Brindley, along with some of my assistance, captured and have now published the main themes of the meeting and the major questions facing the regenerative medicine industry and its rapidly emerging subsets of cellular and gene therapies. 


Notably, we discuss the compatibility of regenerative therapies to the existing healthcare infrastructure, biomanufacturing challenges (including scalability and comparability), and the amenability of regenerative therapies to existing reimbursement and investment models. Furthermore, we reiterate key words of advice from seasoned industry leaders intended to accelerate the translation path from lab bench to the marketplace.


To read the review see: Commercialization of Regenerative Medicine: Learning from Spin-Outs


Anna French, R. Lee Buckler, and David A. Brindley. Rejuvenation Research. April 2013, 16(2): 164-170. doi:10.1089/rej.2013.1423.

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2013 Annual Regenerative Medicine Industry Report

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The Alliance for Regenerative Medicine announced today the release of the 2013 annual regenerative medicine industry report.  Here is the announcement in the Wall Street Journal online.

I'm proud to have been a part of putting it together and hope people find it useful.  It is available for download on the ARM website here.  


In addition to the complete download, ARM will make many of the figures, charts,  tables and sections available for members to download and use in their own publications and presentations. Watch for these resources to be announced soon.


























Source:
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Cell Therapy Blog welcomes 2013

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Happy new year to all our readers.  We look forward to our interactions throughout 2013. This month watch for:
We look forward to seeing you on the 2013 conference circuit.  For a complete and current list of 2013 cell therapy industry conferences, click here.

We will be in San Francisco next week during EBD Biotech Showcase and JP Morgan as well as at the Phacilitate Cell and Gene Therapy Forum in Washington, DC at the end of the month.

As always we welcome your comments, feedback, criticisms, and questions.

Thank you for all for everything to contributed to and did to support this blog and our efforts this past year.  Let's have a great 2013!


p.s.  Don't forget to follow Cell Therapy Blog on Twitter @celltherapyblog 

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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 4ยด,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 DosesBioProcess 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. http://www.incell.com

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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, FACTAABB  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?

Source:
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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/IncomeThis 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. 


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

    By admin



    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 http://www.davidsteenblock.comhttp://www.stemcellmd.org, http://www.strokedoctor.com, http://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.


    Source:
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    Cell Therapy Industry Group Welcomes its 4,000th member

    By admin

    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

    Source:
    http://feedproxy.google.com/~r/CellTherapyBlog/~3/EOlUEgJGsTQ/cell-therapy-industry-group-welcomes.html

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

    By admin


    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


    Source:
    http://feedproxy.google.com/~r/CellTherapyBlog/~3/ctijFXeY01M/gens-cellular-therapy-wave-finally.html

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

    By admin

    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.
    ____________

    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).


    Source:
    http://feedproxy.google.com/~r/CellTherapyBlog/~3/wzhx7dkP3vk/cirm-addresses-some-tough-questions-is.html

    To Read More: CIRM addresses some tough questions. Is it all just glass towers and basic research?
    categoriaRegenerative Medicine commentoComments Off on CIRM addresses some tough questions. Is it all just glass towers and basic research? | dataOctober 21st, 2012
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    Cell therapy portfolio outperforms major indices year-to-date

    By admin



    On August 10 we created a model portfolio in Google Finance of 29 public companies in the cell therapy sector then we compared how that portfolio was doing against the major indices year-to-date (Since 1 January 2012).  See that post here.  Bottom line: even though we are still in a relatively bullish market, the CT portfolio was doing better.  Significantly better.
    So how is the sector portfolio doing now that we've been through three quarters?
    CT model portfolio compared to 3 major indices YTD
    In case you can't read the image above, the blue line represents the cell therapy portfolio and here are the stats on performance since 1 January 2012:
    • Cell Therapy Portfolio:  +24.44%
    • Dow Jones:  +4.5%
    • S+P 500:  +6.78%
    • Nasdaq:  +10.26%
    The only change I've made to the portfolio of 29 companies listed in our August 10 post is to add Thermogenesis (KOOL).  Today its stock is at .968 up from .7 at the beginning of the year.
    You do or should know, I'm no financial analyst.  I'm not entirely sure what assumptions are behind this 'model portfolio' or precisely what one should take from this snapshot but what is clear to me is that at least from one perspective the sector is treating investors fairly well.
    I certainly welcome comments from more sophisticated investors or analysts.  In fact, if anyone with that kind of experience or expertise wants to write a guest post on this blog providing a more sophisticated commentary on what this all means, I would very much welcome the contribution.
    In the meantime, I hope this helps.
    _________________
    Post-publication addition:
    Carter Gould, Associate Biotech Analyst at Dawson James Securities emailed me to point out that the cell therapy portfolio is simply riding the bull wave of biotech in general and and the portfolio has not done even half as well as the broader biotech (BTK) index which is up 45% YTD.  All very true.  Here is a YahooFinance snapshot of the BTK performance vs the three major indices.















    Source:
    http://feedproxy.google.com/~r/CellTherapyBlog/~3/ediPNE1NBDw/cell-therapy-portfolio-outperforms.html

    To Read More: Cell therapy portfolio outperforms major indices year-to-date
    categoriaRegenerative Medicine commentoComments Off on Cell therapy portfolio outperforms major indices year-to-date | dataOctober 14th, 2012
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    Anticipated short-term cell therapy industry clinical milestones

    By admin


    What follows is an interesting but not exhaustive list of cell therapy industry clinical milestones we anticipate in the next 3-9 months as selected from the list of cell therapy products we are tracking in late-stage or post-commercial development.  


    There are other commercial milestones we are monitoring as well as other clinical milestones we expect to see related to cell therapy products in earlier stages of the development pipeline that are not included below.


    CellCoTec (http://www.cellcotec.com)
    • Having completed a trial in Europe of their device to enable POC production of an autologous chondrocyte cellular product in/with a biodegradable, load-bearing scaffold for the treatment of articular cartilage defects, they have now submitted their CE market application.  The CE mark application is under review and they anticipate a response in October.  
    • This device and the potential emergence of Sanofi's MACI in the European market next year may have an impact on Tigenix (EBR:TIG) most directly.



    ERYtech Parma (http://www.erytech.com)

    • Their 'pivotal' phase 2/3 trial in Europe of lead product, GRASPA, for the treatment of Acute Lymphoblastic Leukemia (ALL) is scheduled for completion 2H 2012. 


    GamidaCell (http://www.gamidacell.com)

    • Their 'pivotal' phase 2/3 trial in the US, Israel, and Europe of lead product, StemEx, for the treatment of leukemia and lymphoma, in joint development with Teva, completed enrollment in February and is scheduled for completion 2H 2012.  They have not been shy about the fact they expect to be in the market in 2013.


    Innovacell (http://www.innovacell.com)

    • They raised over 8m Euro in April for a phase 3 trial in Europe for their lead product, ICES13, for the treatment of stress-urinary incontinence which was scheduled for a preliminary clinical data readout in Q4 2012 and be ready for market authorization in 2013. Since announcing the capital raise the company has been stone silent and no clinical trial registry has been filed.  Status unknown.


    Miltenyi Biotec (www.miltenyibiotec.com)

    • Their phase 3 trial in Germany of CD133+ cells as an adjunct to CABG surgery for myocardial ischemia or coronary artery disease is scheduled for completion in January.


    NovaRx (http://www.novarx.com)

    • Their phase 3 trial in US, Europe, and India of their lead product, Lucanix, for the treatment of advanced Non-small Cell Lung Cancer (NSCLC) following front-line chemotherapy is scheduled in clnicaltrials.gov for completion in October but we have learned they expect their next 'interim analysis' in February.


    NuVasive (http://www.nuvasive.com)

    • They have a series of trials scheduled to complete 2H 2012 intended to provide additional clinical data to support its marketing of Osteocel Plus for the treatment of a growing number of orthopedic applications.


    Sanofi's Genzyme (http://www.genzyme.com)

    • Having completed their phase 3 trial in Europe of MACI for knee repair (symptomatic articular cartilage defects of the femoral condyle including the trochlea), they expect to file their market authorization application (MAA) in 1H 2013.


    Hope that's helpful and gives you a sense some of the late-stage things to watch for in the coming weeks and months.  



    --Lee

    Source:
    http://feeds.feedburner.com/CellTherapyBlog

    To Read More: Anticipated short-term cell therapy industry clinical milestones
    categoriaRegenerative Medicine commentoComments Off on Anticipated short-term cell therapy industry clinical milestones | dataSeptember 30th, 2012
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    The cost of clinical trial data bias/loss, FDA’s new job and the need for bold leadership.

    By admin


    The scandal of clinical trial data loss is eroding the fundamentals of evidence-based research and clinical medicine.


    Before you right this post off as the stuff of conspiracy theories, fear-mongering, and 'alternative world views' consider that this view is shared by the likes of the FDA, the International Committee of Medical Journal Editors, the Cochrane Collaboration, and researchers at institutions like Johns Hopkins School of Medicine.


    Here's the underlying premise as succinctly described by author Ben Goldacre:

    "Drugs are tested by the people who manufacture them, in poorly designed trials, on hopelessly small numbers of weird, unrepresentative patients, and analysed using techniques that are flawed by design, in such a way that they exaggerate the benefits of treatments. Unsurprisingly, these trials tend to produce results that favour the manufacturer.

    When trials throw up results that companies don't like, they are perfectly entitled to hide them from doctors and patients, so we only ever see a distorted picture of any drug's true effects. Regulators see most of the trial data, but only from early on in a drug's life, and even then they don't give this data to doctors or patients, or even to other parts of government. This distorted evidence is then communicated and applied in a distorted fashion."

    Authors M. Todwin and J. Abramson summarize it thusly:

    "Trials with positive results generally are published more frequently than studies that conclude that a new drug poses greater risks or is no more effective than standard therapy or a placebo. Furthermore, some articles may distort trial findings by omitting important data or by modifying prespecified outcome measures. Lack of access to detailed information about clinical trials can undermine the integrity of medical knowledge."

    Here is a great list of very recent resources that may convince you of the merits of this concern:

    Yesterday, the US Secretary of Health and Human Services announced (in an FR notice) that the FDA was now charged with ensuring all organizations comply with the heretofore enacted but relatively unenforced  requirement to submit all relevant clinical trial data to http://www.clinicaltrials.gov

    For further commentary on this move see the following reports from:
    What is abundantly clear to me is that the FDA is left almost powerless - and if not powerless than certainly without sufficient resources - to successfully enforce its new power.  This requires collective industry leadership.  Bold, industry-initiated standards, infrastructure and old-fashioned peer pressure.

    Here's what I wish.  

    I wish that as a cell therapy industry we - through organizations like ISSCR, ARM, ISCT, etc and leading publishers of some of our leading journals like Regenerative Medicine, Cytotherapy, Cell Stem Cell, Stem Cells, etc - would take a leadership position on an issue like this.

    I believe that as a relatively small and nascent sector of the biopharma industry we are more likely capable of collaborating on something important like this than larger, more established [entrenched] and diverse sectors.  Of course it requires the political will and cajones.

    The payoff from our sector in taking a leadership role on this issue could potentially be enormous in terms of providing our sector with truly transparent and useful data.  Perhaps even more important would be the public profile such leadership would provide the sector.  Such a move requires bold leadership, pain, and cost but this is the kind of stuff that moves the needle and goes down as critical pivot points in history. 

    Just my thought for the day...

    --Lee

    Source:
    http://feeds.feedburner.com/CellTherapyBlog

    To Read More: The cost of clinical trial data bias/loss, FDA’s new job and the need for bold leadership.
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    Two lessons I learned this week.

    By admin


    I learned two valuable things this week I thought I'd pass on in a Friday afternoon post.  Actually strictly speaking these are likely things I've learned before but needed to re-learn or to be 'reminded' of their importance.
    Please pardon a little stroll away from the typically strict focus on cell therapy -- but in a way that's the theme of today's post.
    1.  Take time each week to read something from outside your specific profession or job focus.  
    I'm not talking here about the importance of escaping in the evening with a fiction novel (also very important) but rather reading something professional but from well outside your area of focus.  Here are my examples.

    I always read WIRED magazine.  Aside from GEN it's the only magazine I read.  Just reading something outside of cell therapy or biotech often infuses me with an idea that otherwise would have never occurred to me like the need for a cell therapy X Prize or cellular aggregates as microcarriers or tissue-engineered memory and processing devices or even just the conviction to better represent cell therapy to the broader world out there of scientists, engineers, journalists, policy-makers, or perhaps people with too much money looking to be inspired and wanting to make a difference.

    Similarly, on a flight this week I reached into the seat pocket in front of me and discovered a recent copy of the Journal of the American Medical Association.  I read a fascinating article that has me excited about an idea for how we as a cell therapy industry might lead the way in addressing clinical trial and data transparency that would put our sector in a leadership position, lend the industry a much-needed spotlight, and has the potential to facilitate the kind of meta-analysis and data-mining that could only be done through data aggregation.  I believe the concept has the potential to be disproportionately significant for a sector defined by so many small, under-powered trials.
    The idea may never see the light of day but the point is the source of the inspiration.  In order to 'think' outside the box one typically has to 'be' outside the box.  Lesson?  Spend some time outside your box.
    2. It often takes something very small to make a disproportionately significant impact on someone.  
    I was reminded recently through an exchange of simple kindnesses just how little it sometimes takes to make a big difference in someone's life.  For you what might be so easy to give might be of unparalleled value to someone for whom that is so unattainable.  
    Lesson?  When the opportunity knocks for you to give something small or simple, take it.  This kind of charity almost always has the potential to be mre impactful than you might ever imagine.

    Source:
    http://feeds.feedburner.com/CellTherapyBlog

    To Read More: Two lessons I learned this week.
    categoriaRegenerative Medicine commentoComments Off on Two lessons I learned this week. | dataSeptember 16th, 2012
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    Are some cell counts too good to be true? Why some companies’ product data may mislead.

    By admin


    This is a cautionary tale about the need for robust product characterization and release specifications for all cell therapy products.
    Background
    While our food often has a list of ingredients, our drugs don't.  We rely on our regulatory agencies to rule on the safety of our drugs.  These agencies require drug manufacturers to submit to them the composition of their therapeutic compounds and then to comply with the product specifications.  It is this composition and these specifications which formed the basis of the clinical data evaluated by the agency and upon which the marketing approval is based.  Any deviation from those specifications requires a submission to the regulatory agency for review. Any deviation without such a submission is punishable.   
    At the manufacturing site, as products come off the line they are subjected to a panel of product release tests to ensure each batch complies with the product specifications.
    Specification compliance is a direct function of the consistency of the raw and ancillary materials, equipment, and operating procedures used in the manufacturing process.



    Cell therapies present unique challenges when complying with this paradigm for several reasons only two of which I will mention here.  Firstly, it is not possible to achieve the level of product purification as one might with other therapeutic products.  Secondly, the product characterization is at a cellular rather than molecular level.

    Autologous cell therapies present another set of unique challenge in this paradigm because of the notable patient-to-patient variability where the patient is also the donor of the raw material.  This often means there is a wider tolerance of heterogeneity in the product but it still must be within what has been proven to the regulatory agency as a safe and effective range.  


    In cases where an autologous cell therapy is centrally manufactured, they are most often subjected to product release testing similar to that described above.  One notable difference, particularly for fresh products, is that the products may be shipped to the clinic and even administered before the full panel of test results are obtained.  This wold be considered highly unusual (if ever acceptable) with other types of products but is tolerated because of the time-sensitivity of these products and their high safety profile.


    In the case of autologous cell therapy products produced at the bedside there is often not the same kind of product release discipline.  Often the regulatory agencies deal with the product consistency and specification compliance issue by ensuring that the cell processing device used point-of-care is validated to ensure the cellular product output is always within a specified range shown to be clinically safe and effective.


    The Varying Degree of Product Characterization/Specification of Autologous GTP Cell Therapy Products


    However - and now I get to the point of this blog post - for cell-based products, procedures and/or devices/kits which are not mandated to be formally approved by a regulatory agency before they can be commercially marketed, there is no product specification rigor.  Compliance with the Good Tissue Practice regulations and guidance is deemed to ensure safety.  In the United States, cell-based products which are deemed to be "minimally manipulated" and intended for "homologous use" are typically allowed to go straight to market with no formal approval.  Safety and clinical data is not required but is practically necessary to support physician adoption and, where applicable, reimbursement.  


    This means that for these products there is a great deal of variability in terms of how much rigor companies apply in characterizing their product and then ensuring that each batch complies with the specifications they themselves have determined to be safe and effective. Again, where such products are manufactured in a centralized facility the likelihood of some release testing is greater.  However, those companies relying on a point-of-care processing kit or device business model that has not been deemed to require formal market approval, rarely (if ever) include product release testing.


    The common criticism of these companies is that they simply do not know what they are injecting into patients because of the combination of the patient-to-patient donor variability, the lack of any disciplined product characterization or dosing studies, and the absence of any product release testing.  


    This criticism is not equally levied at all autologous GTP products or companies - even those relying on point-of-care processing.  Of course some companies care and do a lot to try to ensure their product is well-characterized and that each batch complies with product specifications. This may involve the use of product release tests but can also involve the combination of pre-market research into the product characterization, safety, and dosing along with validation of the device/kit output.  In this way a company can say that within a very small margin, the output will be within the product specifications the company knows is safe and efficacious.


    However, in a rush to get their device/kit to market some companies appear to care very little about the cell product characterization, validation of the output of their device/kit, or tying this data to optimal dose.


    More concerning are those companies that appear to provide such data but it is wrong or meaningless.  What follows appears to potentially be a case study of precisely this problem. 


    The INCELL Study 


    This week I came across a fascinating white paper from Incell Corporation analyzing the output of adipose tissue processing kits of MediVet-America apparently demonstrating the inaccuracy of their cell counts (a common type of cell therapy product characterization) and calling into the question the cell count claims of Intellicell Biosciences (New York, NY) and Adistem (Hong Kong).


    At the heart of the critique is the claim that the cell counting (product characterization) techniques employed by these companies counts as cells things (namely acellular micelles) which are not cells.

    I encourage you to read the white paper in its entirety.  They corresponding author told me to watch for one or more papers which they are preparing for submission to peer-reviewed publications shortly.  Presumably these will rely on a larger data set and perhaps test other methodologies or technologies.


    For the purposes of this blog, I've pulled what I believe are the most salient excerpts below:

    Intrigued by the high cell numbers  (5 to 20 million cells/gram)  reported by kit/device manufacturers such as MediVet-America (Lexington, KY), Intellicell  Biosciences (New York, NY), and Adistem, Ltd. (Hong Kong) in adipose stem cell therapy compared to other methods (e.g., 
    Chung,Vidal, and Yoshimura), INCELL staff conducted a research study to  investigate the high apparent yield of stem cells.  This initial work was focused  on SVF cells from the MediVet Kit, which is marketed to isolate adiposederived canine SVF and stem cells.

    The cell yields reported for the Medivet Kits are five to more than ten times higher than the yields routinely obtained by INCELL from freshly harvested human or animal adipose tissue using our adipose tissue processing methods.  These yields are also tenfold or higher than those reported in the literature by most academic researchers (Chung-canine, Vidal–equine, Yoshimura–human).  Since these  cell counts are used to support stem cell dosing recommendations and cell banking, it is important to better understand why the cell numbers are higher.

    ...

    A comparative analytical study of three dog donors of adipose tissue was designed to evaluate the cell yields using the MediVet Kit as an example of this class of isolation system. All  kit procedures were followed as per the instructions provided.  A brief overview of the different cell counting methods used, and the resultant cell counts, observations and explanations of the results observed, are described below

    ....

    This study shows that incorrect counting of adipose derived SVF cells and the subset of regenerative stem cells can subsequently result in inaccurate dosing, both in direct therapeutic applications and in cryostorage of cells for future use.  The DAPI-hemocytometer cell count (manual) was considered the most accurate, but there are various sources of technical difficulties that  can lead to incorrect  cell numbers. The nature of adipose tissue itself with variability in dissociation by enzymatic digestion can all contribute to the outcomes. Fat tissue has a propensity to form acellular micelles and oils upon tissue disruption. Processing methods or reagents (e.g., Solution E or lecithins) can generate micelles that may be  erroneously  counted as cells. Autofluorescence and dye trapping or uptake by the micelles can lead to very high inaccurate cell counts when automated cell counting is used. 


    In this study the most inaccurate counting came from the Cellometer. When used according to kitrecommended guidelines and on-site training provided by Nexelcom for counting  cells by the MediVet procedure, the Cellometer overstated the DAPI-hemocytometer cell count by up to 20X or more. The Coulter Counter protocols also led to incorrect, high cell numbers. Although the cell counts were still a bit high, the authors recommend the NucleoCounter, or similar equipment, as more acceptable for automated counting.  The manual hemocytometer-DAPI method is the most accurate, but requires a highly experienced cell biologist or technician to make accurate counts and  is not suitable for routine clinical use. 

    ...

    Other companies also have claims of very high cell numbers when their processes are used. Adistem, like MediVet, states they add an emulsifying agent to their kits to assist in cell release, and they also use a light activation system. Their kits were not tested in this study but it is possible that the high cell numbers reported by Adistem are also incorrect and result from the same problems highlighted in this paper for the MediVet procedure. Ultrasonic energy, which is commonly used to manufacture micellular  liposome  structures and to disrupt and lyse cells, is  another potentially problematic procedure for counting and verifying viable, regenerative cells.  Intellicell 3uses ultrasonic energy to release cells from adipose tissue, and it is possible that resultant micelles or cell fragments contribute to the higher than expected cell numbers.  This assumption could be verified with additional studies.  

    In summary, the authors caution that great care must be taken when using kits and automated cell counting for stem cell dosing and cryobanking of cells intended for clinical use. Overestimated  cell numbers would be a major confounding source of variation when efficacy of stem cells injected are compared as doses based on cell number and when cryostored cells are aliquoted for use based on 

    specific cell numbers as a treatment dose.  Hopefully, this study will lead to more  reproducible counting and processing methods being reported in the literature, more inter-study comparability of cell doses to clinical outcomes,  more industry diligence to support claims, and more accurate counting for dosing stem cell therapies to patients.

    ...

    Chung D, Hayashi K, Toupadakis A, et al.  Osteogenic proliferation and differentiation of canine bone marrow and adipose tissue derived mesenchymal stromal cells and the influence of hypoxia.  Res Vet Sci, 2010; 92(1):66-75. Vidal MA, Kilroy GE, Lopez MJ, Johnson JR, Moore RM, Gimble JM. Characterization of equine adipose tissue-derived stromal cells: adipogenic and osteogenic capacity and comparison with bone marrow-derived mesenchymal stromal cells. Vet Surg, 2007; 36:613–622.  Yoshimura K, Shigeura T, Matsumoto D, et al:  Characterization of freshly isolated and cultured cells derived from the fatty and fluid portions of liposuction aspirate.  J Cell Phys, 2006; 205:64-76.

     In Conclusion

    Despite some of their other challenges, Intellicell, MediVet-America, and AdiStem (and others) have scored credibility points with some of my colleagues who have been impressed by the fact that they have incorporated product release criterion and testing technologies into their business model where their peer companies have not bothered.  This credibility may be quickly eroded if it turns out the results of their cell counts have been misleading.  For now it is a word of caution to do your own due diligence and/or not to fall into a similar product development/characterization trap.  Meanwhile, we will watch for the peer-reviewed papers.

    Source:
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    To Read More: Are some cell counts too good to be true? Why some companies’ product data may mislead.
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    Is the cell therapy sector outperforming the major indices?

    By admin


    So here's what I did today.  I built a portfolio of public companies focused exclusively or predominately in the cell therapy space.  I excluded any companies that are in the sector but their products/services constitute less than a significant majority of their revenue and/or expenses.  The portfolio sits at 29 companies.  Here's the list:


    Here's how the portfolio performs against the Dow Jones, Standard and Poor's, and NASDAQ indices so far this year.


    When looking at the period 1 January 2012 to 10 August 2012, the cell therapy portfolio is up 42%, Dow Jones up 8%, Standard and Poor's up 12% and NASDAQ up 16%.

    In the context of how much we hear about how harsh this sector is or has been on investors, I found today's analysis interesting and, honestly, pleasantly surprising.

    This snapshot is useful but has its limitations. I'm relying on Google Finance for accuracy of the information provided.  Do your own due diligence. Invest accordingly.  I hope this helps.

    --Lee

    This snapshot has been brought to you by Cell Therapy Group: all cell therapy, all the time! ๐Ÿ™‚

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    To Read More: Is the cell therapy sector outperforming the major indices?
    categoriaRegenerative Medicine commentoComments Off on Is the cell therapy sector outperforming the major indices? | dataAugust 12th, 2012
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    FDA 1. RSI 0. Regenerative Sciences (Regenexx) vs FDA (2012)

    By admin

    As followers of this blog will know I've been blogging about Regenerative Sciences and predicting their eventual run-in with the FDA since my first post in September 2008 (Cell Therapy is Not the Practice of Medicine) and again in February 2009 (Regenexx vs the FDA 2009).  When the FDA finally proceeded with an injunction against RSI in August 2010,I helped spread the news (here).

    I've watched the development of the fight between RSI and the FDA with interest.  In September 2001 I posted a rather lengthy commentary about the potential impact of the case (Potential far-reaching implications of the ongoing fight over point-of-care autologous cell therapy.

    Since then I have welcomed other bloggers and commentators who are now following and commenting on the case much more closely and frequently than I including @LeighGTurner (on Twitter) and Paul Knoepfler (@PKnoepfler on Twitter and his Knoeplfer Lab Stem Cell Blog).  Recently I enjoyed being interviewed by Paul on the issue of unregulated stem cell activity and touched on the case for his blog.

    Consequently I read with interest yesterday's federal court ruling upholding the FDA's injunction against RSI and the immediate commentary from the New Scientist, Stanford's Scope Blog and Knopfler's multiple posts (here and here). As a long-term follower of this case, I've been asked to comment.  Here is my brief reaction:

    This is a case that was always destined for the appellate courts regardless of which way the initial court ruled.    The fact the federal court ruled in the FDA's favor certainly now sets the onus on RSI and what is anticipated to be a gamut of intervenors but taking this case to the appellate courts is what the legal team have anticipated and legal arguments designed for all along.

    This is just the beginning of what will be a long and interesting battle.  The ruling was nothing more than the granting of an injunction in response to the government's motion for summary judgement.  In granting the injunction the court  agreed with the government's position that it was acting under the authority given it under the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 321(g) but it provided little-to-no rationale for its ruling.

    The court chose, in its wisdom, not to address the bulk of the RSI's legal arguments which are largely jurisdictional in nature. These are the kinds of arguments which the lower courts prefer be dealt with by appellate courts and frankly the judge did us all a favor by ruling quickly, succinctly and punting the case where we all knew it was inevitably headed.

    In my opinion, other than chalking one up in the government's win column there is little to be gleaned from this ruling in terms of how RSI's arguments will be received in appellate court.  The interesting day is yet to come.

    In terms of a short-term practical impact, frankly I see very little.  RSI has already ceased distributing Regenexx within the US so there will be little-to-no impact there.  As for the potential impact on other companies or clinics who might be operating on the fringes of FDA regulation within the US, I suspect it will be business as usual.

    Most of the clinics/companies offering cell-based treatments/products which are arguably in contravention of FDA regulation are operating under the clear knowledge of what they are doing and where the FDA stands with respect to the treatments/products they offer and yet they persist and continue.


     For the truly fraudulent there is the risk of criminal charges and/or litigation but for those companies or practitioners who are operating in this shade of grey which are not shady (and they do exist), the  risks associated with this practice are barely higher than in the routine practice of medicine. 


    In reality, with the exception of the most fraudulent examples, it takes a fair long-time for the FDA to catch up with these folks and there is good money to be made in the interim.  When they get caught, they will stop. If they've recouped their initial investment (which is nominal and the margins are high) there is very little penalty to this course of action.  Perhaps they set up shot elsewhere or simply enjoy the proceeds.  I doubt we will see much of a slow-down of this kind of activity.  Indeed it may strengthen the resolve of those committed to the cause.

    In my opinion yesterday's ruling was in interesting and important milestone in a continuing evolution in the debate of how best to regulate the use of cells in treating people but I'm not sure it's the seminal pivot point that some believe.  I suspect we will not see any radical shift in terms of FDA or industry activity until (if then) the appellate courts rule.

    Just my two cents....

    --Lee

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    To Read More: FDA 1. RSI 0. Regenerative Sciences (Regenexx) vs FDA (2012)
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    Bioreactor Design and Bioprocess Controls for Industrialized Cell Processing

    By admin

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    A short and sweet note to point you to a great article on bioreactor technologies related to cell therapy bioprocessing by CTG consultant and Director of Stem Cell-based Drug Discovery, John E. Hambor, who you can now follow on Twitter @StemCellonDrugs.


    "Bioreactor Design and Bioprocess Controls for Industrialized Cell Processing" was published in the June issue of BioProcess International.  


    The BPI team has made a real and meaningful commitment to representing cell therapy bioprocessing and we applaud them for their contribution to this emerging discipline.




    If this is a topic of interest to you, I recommend you also check out a conference being held this Fall by BPI's sister company, IBC LifeSciences, entitled "Cell Therapy BioProcessing" to be held September 11-12 in Arlington, Virginia.





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    To Read More: Bioreactor Design and Bioprocess Controls for Industrialized Cell Processing
    categoriaRegenerative Medicine commentoComments Off on Bioreactor Design and Bioprocess Controls for Industrialized Cell Processing | dataJune 17th, 2012
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    Industry-sponsored cardiovascular cell therapies. Some metrics.

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    Cell therapies for cardiovascular-related conditions is a closely watched, much studied, oft-discussed, and hotly contested segment of the cell therapy industry.


    The data to-date are admittedly confusing.  From a clinical perspective, the studies for which we have data have been relatively small involving a mish-mash of indications, endpoints, eligibility criterion, methods and/or route of administration, as well as the time of administration relative to event or disease progression.


    Further compounding any interpretation of the data, from a technical perspective, is the fact the products have been widely varied in terms of being autologous vs allogeneic, expanded and not, genetically modified and not, from a plethora of different sources, and utilizing a wide variety of cell types from skelatal myoblasts, cardiomyocytes, mesenchymal stromal cells, mononuclear cells, etc. 


    All this makes it extremely difficult to draw any conclusions with respect to what's working and what's not.  We will not attempt to do so.


    All we do below is attempt to give a snapshot of the industry-sponsored cell therapy trials currently ongoing for cardiovascular-related conditions.  So here it is:


    Commercial:
    Pharmicell's Heartcelligram is the only cell therapy to have received regulatory approval for commercial distribution for the treatment of a cardiac-related indication.  Heartcelligram is an autologous cell therapy approved in 2011 by the Korean Food and Drug Administration (KFDA) for the treatment of Acute Mycardial Infarction (AMI).  The price is reportedly $19,000 and the trial data behind the approval has not yet been published in a peer-reviewed journal.


    Phase III or II/III:
    There are currently only 3 active and recruiting cardiac-related, industry-sponsored cell therapy trials.  Interestingly they all involve autologous products, two involve devices, two involve centralized manufacturing, two involve bone marrow cells as a source, two are only in European clinical sites, and two are targeting ischemic-related conditions.

    • Baxter Therapeutics' Auto-CD34+ cells
    • Cytori
    Two companies warrant particular mention at this stage as they appear to be in transition between phases II and III.

    Cardio3 Biosciences initially designed a trial of their autologous C-Cure in heart failure secondary to ischemic cardiomyopathy to be a phase II/III trial enrolling 240 patients.  While the trial began in late 2008 and is still registered as active but no longer recruiting on ClinicalTrials.gov the entry has not been updated for almost a year.  

    In 2010 the company announced that after enrolling 45 patients - of which 21 were in the treatment arm (24 in the control arm) - they decided to close the study to future enrollment and prepare for a phase III trial.  This decision was reportedly based on "very encouraging data". 

    Dr. Christian Homsy, CEO of Cardio3 BioSciences provided the following guidance: “The highly promising data we report today build on the favourable safety profile we have observed through this Phase II trial and documents in patients our belief that we have with  C-Cure a product candidate with the potential to make a real difference in the treatment of heart failure... As noted in the company’s press release of 29 June 2010, with the Phase II stage completed and to allow for potential modifications to the trial protocol, Cardio3 BioSciences has not proceeded to Phase III recruitment into the trial but has continued to gather all data for the six month analysis. Through the Phase II trial, we gained significant  experience in working with a highly innovative stem cell therapy in a clinical setting, and we are using this acquired knowledge in the design of our planned Phase III programme."  The phase III trial of C-Cure is expected to commence in the second half of 2012.

    Mesoblast has also announced with its strategic partner, Teva, that they are proceeding with plans to conduct a phase III study of its allogeneic cell therapy product, Revascor, in chronic heart failure.  Most anticipate this clinical trial application to be filed sometime in late 2012.


    Phase I or II:
    There are over 20 active, industry-sponsored earlier-stage trials (phase I, I/II or II) for cardiovascular-related conditions.  At least 5 of these are expected to have clinical readouts this year.   



    Hope this is useful.

    --

    This post has been brought to you by your friends at CTG.  All cell therapy. All the time. ๐Ÿ™‚  

    -- Lee @celltherapy

    p.s.  As always we welcome your feedback, comments, and corrections.  
























































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    To Read More: Industry-sponsored cardiovascular cell therapies. Some metrics.
    categoriaRegenerative Medicine commentoComments Off on Industry-sponsored cardiovascular cell therapies. Some metrics. | dataMay 27th, 2012
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    Cell-based Cancer Immunotherapies. Some metrics..

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    Whatever one makes of Dendreon's challenges in bringing Provenge to market and then its ups and downs in the market, the whole affair has brought a much bigger spotlight to cancer immunotherapies and cell-based immunotherapies in particular.

    This is true on all fronts.  Cancer immunotherapy conferences are popping up everywhere.  A growing number of of analysts are now covering a growing number of companies in the space with coverage ranging from bearishly critical to ebullient bullishness. Some venture capital firms are now loosening their purse strings for immunotherapy plays and both pharma venture funds and business development departments are now spending an increasing amount of time actively monitoring and exploring potential plays in the sector.



    One of the best annual industry summaries of what is happening in the sector is sponsored by MD Becker Partners through its annual Cancer Immunotherapy: A Long Awaited Reality conference held each in New York, this year on October 4 and select video replays it hosts on its YouTube channel.

    Some Segment Metrics
    As part of our ongoing industry intelligence and consulting services we actively track the activity and progress of industry-sponsored clinical trials of all cell therapies in addition to the products already on the market.  Here's how our data stacks up regarding the cell-based immunotherapies segment of the sector:
    Commercial:
    • Dendreon's Provenge
      • Autologous immunotherapy for prostate cancer (1 monthly dose for 3 months)
      • Efficacy: prolongs survival
      • Markets: only the United States (approved April 2010)
      • Next markets: submitted the marketing authorisation application to the EMA (European Medicines Agency) in early 2012 and hopes to introduce Provenge in the European market in 2013
      • 2011 Revenue $290,000
      • Projected 2012 Revenue: ~$380,000

    Phase III or II/III:

    Phase II or I/II

    • 50 industry-sponsored clinical trials of cell-based immunotherapies actively recruiting, active no longer recruiting, active not yet recruiting, or anticipated to commence yet in 2012
      • ~10 of these are expected to have readouts yet this year
      • Trial sites in US, Canada, UK, continental Europe, Israel, South Korea, India, Australia
      • Expected enrollment of 3,500+
    Investment:

    The following are notable cash infusions into the sector for 2012 to-date:
    • Bellicum Pharmaceuticals.  $20M series B. 
    • CellMedica. $15M grant from CPRIT in Texas.
    • Argos Therapeutcs. $25M Series D.
    • Northwest Bio.  $5.5M grant from German gov't Saxony Development Bank

    Hope this is useful.

    --

    This post has been brought to you by your friends at CTG.  All cell therapy. All the time. ๐Ÿ™‚  

    -- Lee @celltherapy

    p.s.  As always we welcome your feedback, comments, and corrections.  












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    To Read More: Cell-based Cancer Immunotherapies. Some metrics..
    categoriaRegenerative Medicine commentoComments Off on Cell-based Cancer Immunotherapies. Some metrics.. | dataMay 20th, 2012
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