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.
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).