Program to Advance Development of Drug Candidates for Rare and Neglected Diseases

THIS IS NOT A SOLICITATION NOTICE - THIS IS A REQUEST FOR INFORMATION (RFI) ONLY. Background -- In March of 2009, the National Institutes of Health (NIH) was authorized by Congress to set up a therapeutics development program for rare and neglected diseases hereafter named the Therapeutics for Rare and Neglected Diseases program (TRND), which would also develop innovative research processes for preclinical drug development. For the purposes of TRND, rare diseases are defined according to the Orphan Drug Act of 1983, and as amended in 1984, 1985, and 1988, affecting fewer than 200,000 people in the United States; neglected diseases are defined according to the World Health Organization, being primarily tropical infectious diseases that are highly prevalent in the developing world. The NIH estimates that more than 6,800 rare diseases afflict more than 25 million Americans. However, effective pharmacologic treatments exist for only about 200 of these illnesses. The new TRND Program operates scientifically and administratively through the National Human Genome Research Institute (NHGRI) with oversight by the NIH Office of Rare Diseases Research (ORDR). To jump-start TRND, NIH is considering initiating projects with promising drug candidates that are stalled in development for which there are clinical data, or for which a data package could be generated and compiled into an Investigational New Drug (IND) submission within one year of transfer of the project to TRND. Responses to this RFI will be used to formulate a Request for Proposal (RFP) to acquire drug programs, expected to be published in May, 2010 with a proposal submission deadline in June, 2010. The RFP would initiate a process for TRND to purchase by contract award by September 30, 2010, the most promising compounds for their development by TRND at NIH's expense. Alternatively, the information received through this RFI may be used to negotiate Cooperative Research and Development Agreements (CRADAs) with program owners who wish to have their candidate compounds developed by TRND but who are unwilling or unable to sell the Programs in their entirety to NIH. Description -- The new NIH Therapeutics for Rare and Neglected Diseases program (TRND), located in Bethesda, Maryland, is creating an Research and Development (R&D) infrastructure to develop small molecule lead compounds for a broad range of rare and neglected diseases. To jump-start the activities of this new program, the NIH wishes to acquire full ownership of a small number of rare or neglected disease drug discovery candidate compounds, intellectual property, associated analogs and know-how (Programs), and to advance them at its own cost through to the human clinical trials proof-of-concept stage. An R&D portfolio strategy is being developed, and focus areas are being defined. The purpose of this RFI is to identify what Programs may be available from biotechnology companies, pharmaceutical companies, nonprofit organization, universities, or other organizations, and to notify the research community that TRND intends to acquire and develop these types of drug programs. NIH is particularly interested in learning what small molecule drug discovery programs for rare and neglected diseases are either stalled or are at risk of being stalled, and characteristics of those programs that might make them candidates for an accelerated drug development program such as TRND. Relevant candidate drug projects may be in various stages, from robust research probe to Phase I clinical trials. At a minimum, compounds must have drug-like properties using biopharmaceutical industry standards, and data showing reproducible activity, structure activity relationship (SAR), and efficacy in a variety of cellular and/or animal model systems; demonstration of favorable in vitro and/or in vivo ADMET (absorption, distribution, metabolism, excretion and toxicity) properties is required for later stage compounds. Compounds beyond the research probe stage should generally be protected by U.S. or world-wide patents. The compounds may be repurposed drug candidates meaning that they have been developed for a common disease indication, but during the development process, they were also found to show promise for a rare or neglected disease indication. The NIH is particularly interested in learning about drug candidates that meet biotechnology or pharmaceutical company drug development program entry criteria, but are stalled for financial or strategic reasons. NIH is requesting information on the existence of compounds at these stages of development, in the following order of priority: 1. Open US IND application with existing human data; 2. Open IND, but no human data; 3. IND-enabling data exist but the IND has not yet been written or submitted to the Food and Drug Administration (FDA); 4. A drug candidate compound in late stage pre-clinical development and back-up compounds for a specific drug target that would require no more than 6 to 12 months of further pre- clinical profiling to be ready for an IND enabling toxicology and ADMET program; and 5. A research probe compound. Information Requested -- The NIH solicits the following information in summary form: 1. Rare or neglected disease(s) for which the compound is being developed 2. Compound name a. Chemical structure of the compound b. Company designation c. Brand name, if any 3. A summary of the status of the program 4. The owner of the intellectual property (IP) associated with the compounds and research data 5. A summary of the US and international patents issued or patent applications, and their status 6. Any known blocking IP that would prevent transferring the compound to a third party for development 7. Why the compound is stalled or at risk of being stalled in development 8. Details on the most advanced stage of development 9. If applicable, whether good manufacturing practice (GMP) compound is available for clinical trials 10. Pre-clinical data a. Summary data of biological activity against the target in vitro in human cells (potency, efficacy, and SAR data) b. Summary data of biological activity against the target in vivo in animal models (potency, efficacy, and SAR data) c. Summary data from drug metabolism and pharmacokinetics profiling i. In vitro ii. In vivo small and/or large animal d. Summary data from drug substance profiling and pharmacologic development processes e. Summary data from toxicology profiling i. In vitro ii. In vivo small and/or large animal 11. Clinical data a. Summary human safety b. Summary human dosing data c. Summary human tolerability d. Summary human proof of concept (POC) data i. Biomarkers ii. Surrogate endpoint(s) iii. Clinically meaningful outcome measures 12. How many compounds in the same chemical series exist 13. Mechanism of action of the drug candidate 14. Information on the: a. Pharmacophore of the compound b. 3-D structure of the drug target (with or without the compound bound) How to Submit a Response -- The response must include: (1) Company/Organization Name; (2) Company/Organization Address; (3) Point of Contact Name; (4) Point of Contact Telephone Number; and (5) Point of Contact email address. The response must be in the format as outlined under the paragraph titled - Information Requested. Responses to this RFI announcement must be received not later than 5:00 p.m., on March 31, 2010. Responses must be submitted by e-mail with the documentation attachment to Eric M. Nelson, Ph.D. at trnd@mail.nih.gov and Debra Hawkins, Contracting Officer, National Heart, Lung, and Blood Institute (NHLBI) at dh41g@nih.gov, with a subject line of: Response to RFI # NHLBI-NHGRI-2010-112. Specific technical questions about this RFI must be provided in writing by email to trnd@mail.nih.gov. No questions will be entertained via telephone contact. Disclaimer and Important Notes -- This notice is a request for information only. This notice is not a Request for Proposal, a Request for Quotation, an Invitation for Bids, a solicitation, or an obligation on the part of the Government to acquire any products or services. This notice is not to be interpreted as a commitment by the U.S. Government. It is not an opportunity to acquire funding to support current or future development efforts. This notice does not obligate the Government to award a contract. No entitlement to payment of direct or indirect cost or charges to the Government will arise as a result of a submission of responses to this announcement or the Government's use of such information. The Government reserves the right to use information provided by respondents for any purpose deemed necessary and legally appropriate. Any organization responding to this notice should ensure that its response is complete and sufficiently detailed. Information provided will be used to assess tradeoffs and alternatives available for the potential requirement and may lead to the development of a solicitation. Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted. Any solicitation resulting from the analysis of information obtained will be announced to the public in Federal Business Opportunities (FedBizOpps) in accordance with the Federal Acquisition Regulations (FAR) Part 5 - Publicizing Contract Actions. However, responses to this notice will not be considered responses to a solicitation. All proprietary, classified, confidential, or sensitive information included in your response must be identified and appropriately marked. It is suggested that any response to this notice, that includes data that the respondent does not want disclosed to the public for any purpose, or used by the Government except for evaluation purposes, shall mark each sheet of restricted data with the following legend: - This response includes data that shall not be disclosed outside the Government and shall not be duplicated, used, or disclosed in whole or in part for any purpose other than for evaluation purposes. In the absence of such identification, the Government will assume to have unlimited rights to all data submitted.