Here’s an interesting funding opportunity from NIH:
Recent advances in neuroscience offer unprecedented opportunities to discover new treatments for nervous system disorders. However, most promising compounds identified through basic research are not sufficiently drug-like for human testing. Before a new chemical entity can be tested in a clinical setting, it must undergo a process of chemical optimization to improve potency, selectivity, and drug-likeness, followed by pre-clinical safety testing to meet the standards set by the Food and Drug Administration (FDA) for clinical testing. These activities are largely the domain of the pharmaceutical industry and contract research organizations, and the necessary expertise and resources are not commonly available to academic researchers.
To enable drug development by the neuroscience community, the NIH Blueprint for Neuroscience Research is establishing a ‘virtual pharma’ network of contract service providers and consultants with extensive industry experience. This Funding Opportunity Announcement (FOA) is soliciting applications for U01 cooperative agreement awards from investigators with small molecule compounds that could be developed into clinical candidates within this network. This program intends to develop drugs from medicinal chemistry optimization through Phase I clinical testing and facilitate industry partnerships for their subsequent development. By initiating development of up to 20 new small-molecule compounds over two years (seven projects were launched in 2011), we anticipate that approximately four compounds will enter Phase 1 clinical trials within this program.
My first thought is that I’d like to e-mail that first paragraph to Marcia Angell and to all the people who keep telling me that NIH discovers most of the drugs on the market. (And as crazy as that sounds, I still keep running into people who are convinced that that’s one of those established facts that Everyone Knows). My second thought is that this is worth doing, especially for targeting small or unusual diseases. There could well be interesting chemical matter or assay ideas floating around out there, looking for the proper environment to have something made of them.
My third thought, though, is that this could well end up being a real education for some of the participants. Four Phase I compounds out of twenty development candidates – it’s hard to say if that’s optimistic or not, because the criteria for something to be considered a development candidate can be slippery. And that goes for the drug industry too, I hasten to add. Different organizations have different ideas about what kinds of compounds are worth taking to the clinic, and those criteria vary by disease area, too. (Sad to say, they can also vary by time of the year and the degree to which bonuses are tied to hitting number-of-clinical-candidate goals, and anyone who’s been around the business a while will have seen that happen, to their regret).
It’ll be interesting to see how many people apply for this; the criteria look pretty steep to me:
Applicants must have available small-molecule compounds with strong evidence of disease-related activity and the potential for optimization through iterative medicinal chemistry. Applicants must also be able to conduct bioactivity and efficacy testing to assess compounds synthesized in the development process and provide all pre-clinical validation for the desired disease indication. . .This initiative is not intended to support development of new bioactivity assays, thus the applicant must have in hand well-characterized assays and models.
Hey, there are small companies out there that don’t come up to that standard. To clarify, though, the document does say that “Evaluation of the approach should focus primarily on the rationale and strengths/weaknesses of proposed bioactivity studies and compound “druggability,” since all other drug development work (e.g., medicinal chemistry, PK/tox, phase I clinical testing) will be designed and implemented by NIH-provided consultants and contractors after award”, which must come as something of a relief.
What’s interesting to me, though, is that the earlier version of this RFA (from lsat year) had the following language:
The ultimate goals of this Neurotherapeutics Grand Challenge are to produce at least one novel and effective drug for a nervous system disorder that is currently poorly treated and to catalyze industry interest in novel disease targets by demonstrating early-stage success.
That’s missing this time around, which is a good thing. If they’re really hoping for a drug to come out of four Phase I candidates in poorly-treated CNS disorders, then I’d advise them to keep that thought well hidden. The overall attrition rate in the clinic in CNS is somewhere around (and maybe north of) 90%, and if you’re going to go after the tough end of that field it’s going to be even steeper.