Small Molecule Drug Prototyping

The Stanford Innovative Medicines Accelerator (IMA) is accepting proposals that address two major challenges in small-molecule drug discovery: identifying medicinal leads and optimizing medicinal leads into drug prototypes. Through this call, the IMA is soliciting Letters of Intent (LOI) for projects that fall under one of the following modules:

• High-Throughput Screening: Includes support for the development, optimization, and miniaturization of a biochemical or a cell-based assay in 384-well microplate format for use in high-throughput, small-molecule screening. Pending successful assay development, funding also includes support for the high-throughput screen. Competitive projects require a strong, novel therapeutic hypothesis and aim to identify small molecule leads for a defined molecular target.
• Small Molecule Drug Prototyping: Engineering one or more small molecule leads to improving their potency, selectivity, pharmacokinetics, and/or pharmacodynamics with the goal of identifying a high-quality, patentable drug prototype. Competitive projects will have a strong therapeutic hypothesis, a novel biological target, one or more small molecule leads as starting points for medicinal chemistry, and appropriate assays for lead optimization.

The IMA aims to accelerate the translation of scientific discoveries at Stanford University into new medicines through prototyping of innovative therapeutics and vaccines while enabling hypothesis-driven studies that impact human health. Basic research, including target identification, is outside the scope of the current LOI solicitation.

Support Provided: 

Projects selected through this call for proposal will receive support through one or more of the following IMA modules:

• High-throughput Screening: Selected projects will receive access to the Sarafan ChEM-H / Chemical and Systems Biology High-Throughput Screening Knowledge Center (HTSKC). Support will include access to HTS compound libraries, instrumentation fees, associated consumables, expert training, and advice in assay development for high-throughput screening projects.
• Small Molecule Drug Prototyping: Selected projects will receive access to the ChEM-H Medicinal Chemistry Knowledge Center (MCKC) to facilitate the design, synthesis, and screening of novel small molecules to identify lead drug prototypes. Support will focus on improving pharmacodynamics and pharmacokinetics of established molecular targets.
• In vitro and in vivo Pharmacology: Projects requiring the establishment and/or scale-up of in vitro and/or in vivo assays (including the use of appropriate disease models) to achieve their goals will receive appropriate support of this nature from the IMA’s Preclinical Pharmacology module.

Depending on the nature and requirements of each project, the IMA will provide access to strategic alliances and vetted contract research organizations (CROs) to support awarded projects.

Each of the above modules is led by a senior research staff member who will collaboratively help the PI of selected projects to formulate a goal- and milestone-driven project plan. Awarded projects will be supported for 6–24 months, with critical milestone decision points defined for this project period. Further details regarding specific roles and responsibilities of the personnel support and the financial allocations will be elaborated in individual Award letters issued to selected projects. The specific level of support will vary by project need.

Deadline: 

All LOIs must be received by 5 pm, June 2, 2023. The most promising proposals will be selected for full proposal development.

Eligibility: 

All Stanford faculty with PI eligibility are eligible to apply.

Application Instructions:

LOIs should be submitted as single PDF files containing the following materials in the order indicated below. All documents must be single-spaced, Arial 11-point font with 1-inch margins.

1. Title page (1 page): Project title; Investigator name(s), department, address, phone number, email address, and a project summary for a lay audience (150 words max).
2. Letter of Intent (3 pages maximum):
   1. High-throughput Screening: Briefly describe the therapeutic hypothesis and the case for the biological target of the anticipated high-throughput assay development effort. Provide a technical summary of the assay you wish to miniaturize as well as potential secondary assays. Include details on availability of protein structure and access to materials required for the assay (cell lines, purified proteins etc).
   2. Small Molecule Drug Prototyping: Briefly describe the therapeutic hypothesis and the case for the biological target of the anticipated small molecule prototyping effort. Provide justification for the molecular target and identify milestones that would overcome a specific hurdle toward Drug Prototyping. Describe studies that would enable de-risking of foundational technology necessary for pre-clinical development. Faculty who are unsure of whether their project fits within the high-throughput screening or drug prototyping module are encouraged to contact Prof. James Chen (jameschen@stanford.edu) or Prof. Nathanael Gray (nsgray@stanford.edu) for advice.
3. NIH-format biosketch for each investigator

LOIs should be submitted directly through the SlideRoom portal. Once in the portal, you will be directed to select one of the two IMA modules. Please select the one most appropriate for your proposed research.

You do not need to submit your applications to your Research Process Manager (RPM) in RMG or through your Office of Sponsored Research (OSR) Contract and Grant Officer (CGO) for their approval at this time.

Selection Process:

A committee of faculty reviewers will identify the most meritorious LOIs based on:

• Novelty of the therapeutic hypothesis
• Level of chemical/biochemical innovation of the prototype
• Significance of the unmet medical need
• Feasibility of support via available IMA mechanisms/resources

PIs whose project ideas are selected will be invited to submit full proposals; they will have the option of formulating these proposals independently or with the help of a senior staff member of the respective module. Final decisions on full proposals will be made by mid-Fall 2023.