Notice Number: NOT-MH-11-015
Key Dates
Release Date: July 19, 2011
Issued by
National Institute of Mental Health (NIMH)
Purpose
The purpose of this Notice is to alert small businesses to high program priorities relevant to the SBIR program of the National Institute of Mental Health (NIMH). A significant interest for the NIMH is the support of small businesses engaged in drug development activities, and specifically in supporting Phase I and Phase IIa clinical trials of novel clinical candidates for the treatment of mental disorders. The clinical trials are expected to include biological/behavioral data to assess target engagement and to help determine potential success or failure of the compound before moving on to larger clinical trials. This high priority also applies to small businesses interested in these early stage clinical trials to advance the testing of novel therapeutic agents for HIV/AIDS-associated neurocognitive disorders (HAND).
Background
For more than a decade, the failure rate for central nervous system (CNS) drugs at very late stages of development has been high and extremely costly. This situation has contributed to the decrease in Pharma’s investment in psychiatric drug development and HAND drug development, effectively broadening the “valley of death” for drug development in these areas. During this period of time NIMH has provided funding support and research resources to facilitate drug discovery/development of novel medications for mental disorders through several avenues:
- PA-11-133(R43/R44) - NIMH SBIR/STTR Programs
- PAR-11-206(UM1) and PAR-11-207(U19) - National Cooperative Drug Discovery/Development Groups (NCDDG) for the Treatment of Mental Disorders, Drug or Alcohol Addiction
- PAR-10-001(R01) and PAR-10-002(R21) - Drug Discovery for Nervous System Disorders
- PAR-10-216(P01) - Novel NeuroAIDS Therapeutics: Integrated Preclinical/Clinical Program
- The NIMH Psychoactive Drug Screening Program
- The NIMH Toxicological Evaluation of Novel Ligands Program
- The NIMH Chemical Synthesis and Drug Supply Program
These funding opportunities/resources generally have focused predominantly on the preclinical stages of drug development. A recently published report of the National Advisory Mental Health Council’s Workgroup, entitled, From Discovery to Cure: Accelerating the Development of New and Personalized Interventions for Mental Illness evaluated NIMH’s portfolio and funding opportunities/resources for drug discovery/development in light of the current trend of Pharmaceutical companies and venture capital to decrease their investments in clinical trials for CNS disorders. A main recommendation identified by this workgroup was for NIMH to invest in early stage clinical trials of novel compounds which act on molecular pathways (receptors, enzymes, second messengers, etc.) that are not typically targeted with currently available psychiatric drugs, and that have a strong biological justification as a novel mechanism for treatment of psychiatric disorders. In addition, a recommendation was made to provide supplementary biological/behavioral measures in the trials that can be used to assess target engagement and/or evaluate the compound’s mechanism of action in humans. The incorporation of these additional measures into standard trials is intended to provide very early signs of potential failure or success of the compound, determine best starting doses for proof of concept trials, and help inform whether further later stage trials should be considered.
This Notice encourages small businesses to take part in this effort to speed the translation of preclinical compounds into human trials through the SBIR program.
Opportunity to Support Early Stage Clinical Trials
The goal of this notice is to fill the funding gap that currently exists for small businesses, in the early clinical stages of drug development for mental disorders or HIV/AIDS-associated neurocognitive disorders, and provide funding to support clinical studies exploring pharmacological and functional effects of compounds in order to attract private funding for further clinical and commercial development.
NIMH is specifically encouraging the submission of SBIR Fast Track, Phase II or Phase IIb grant applications through PA-11-133 - Complex Technologies and Therapeutics Development for Mental Health Research and Practice (R43/R44), which supports Phase I and Phase IIa (proof of concept) clinical trials:
Phase I (first in human) clinical trials: will include initial dose range finding studies and assess safety and tolerability and pharmacokinetics in normal subjects. Additionally, the trial should include measures of CNS drug activity/target engagement and pharmacological effect, using validated physiological and/or objective behavioral biomarkers. Results obtained in this first in human trial could be carefully integrated with preclinical data to reach a “best guess” starting dose for the future pilot proof of concept trial, (see AF Cohen, Developing drug prototypes: pharmacology replaces safety and tolerability? Nature Reviews Drug Discovery 9, 856-865, 2010).
Phase IIa (pilot, proof of concept) clinical trials: will include an evaluation of efficacy and safety in a select population of patients with mental disorders or HAND, assess CNS drug activity/target engagement in subjects and measure the impact on clinically relevant physiological systems.
The goal of these added (experimental) measures is to determine if a compound designed to target a biological mechanism or pathway that is implicated in a disorder actually engages the target in humans and affects brain physiology as predicted by supporting preclinical data and basic science research. Therefore, a strong scientific rationale should be provided in the application to address the measures selected for the trial. Additionally, subject selection should be well justified and the application should detail steps taken to ensure the individuals have the abnormality in the CNS pathway being studied.
Compounds to be tested should be cleared by the FDA as an Investigational New Drug (IND).. Compounds acting on molecular targets that replicate those of currently-marketed pharmaceuticals are not of interest for this initiative. Testing of compounds that have been FDA-approved for other indications (repurposing) are of interest if recent basic research discoveries suggest that the compound(s) have the potential to affect a biological mechanism contributing to mental disorders that has previously been untested in clinical studies.
The trials must be performed in the United States. The inclusion of collaborations between a small business and the clinical researchers with expertise in clinical trial design and the methods proposed to measure target engagement is encouraged.
How to Apply
Applicants may apply for these high program priorities using PA-11-133 when submitting an application.
Eligibility
Eligibility information, review information and all other aspects of the application process are described in PA-11-133.
Budget and Funding Information
Budgets requested for the trials should be well justified and cost sharing, including in-kind support, is strongly encouraged. Applicants are strongly encouraged to contact program staff before submitting an application.
Although these early stage clinical trials are considered a high priority to the NIMH SBIR program, all other aspects of PA-11-133 remain the same.
Inquiries
Inquiries regarding this Notice may be directed to:
Margaret C Grabb, PhD
NIMH SBIR/STTR Coordinator
National Institute of Mental Health
6001 Executive Boulevard, Room 7201, MSC 9645
Bethesda, MD 20892-9645
Telephone: (301) 443-3563
Email: [email protected]
and Human Services (HHS)
