Molecular Therapeutics

The Innovative Medicines Accelerator (IMA) aims to accelerate the translation of scientific discoveries at Stanford University into new therapeutics that impact human health. Identification of medicinally appropriate lead molecules and their subsequent engineering into Drug Prototypes are two major challenges in drug discovery. Through this broad call for proposals, the IMA is soliciting Letters of Intent (LOI) for projects that fall under one of the following modules:

• High-Throughput Screening Assay Development: Assay development projects to create and optimize miniaturized assays in 384-well microplate format for use in high-throughput, small-molecule screens. Competitive projects will have a strong, novel therapeutic hypothesis and aim to identify small molecule leads for a molecular target or cellular phenotype
• Small Molecule Drug Prototyping: Identifying new medicinal leads and/or engineering them into Small Molecule Drug Prototypes. Competitive projects will have a strong therapeutic hypothesis, a novel biological target, and one or more bioactive small molecules as starting points.
• Prototyping of Protein Therapeutics: Discovery of a protein/antibody with sufficiently promising properties to be advanced as a drug prototype. Competitive projects will have a strong therapeutic hypothesis and a novel biological target whose activity can be enhanced or blocked by a natural or engineered protein.

Basic research, including research directed towards target identification, is outside the scope of the current LOI solicitation.

Support Provided:

• High-throughput Screening Assay Development: Selected projects will receive access to the ChEM-H / CSB High-Throughput Screening Knowledge Center (HTSKC) facility, which includes instrumentation fees, associated consumables, and expert training and advice in assay development for high-throughput screens (384-well microplate format).
• Small Molecule Drug Prototyping: Selected projects will receive access to the ChEM-H Medicinal Chemistry Knowledge Center (MCKC) to facilitate the engineering of a novel medicinal lead molecule or drug prototype.
• Prototyping of Protein Therapeutics: Selected projects will receive access to the ChEM-H Protein Engineering Knowledge Center (PEKC) facility for tasks such as discovery of a monoclonal antibody to serve as a therapeutic lead, structure-based and/or evolutionarily guided optimization of a lead antibody or non-antibody protein therapeutic and recombinant protein production for structure-activity relationship analysis.

Depending on the nature and requirements of each project, the IMA will provide access to strategic alliances and vetted CROs to support the project. If needed, projects will also receive access to the IMA’s Pharmacology module for in vitro and in vivo PK/PD analysis and for evaluating the efficacy of the most promising drug prototypes in a suitable disease model.

Each of the above modules is led by experienced faculty and senior research staff members who will collaboratively help the PI of each selected project formulate a goal- and milestone-driven project plan. The IMA will support all of the work defined in the workplan other than that which is performed in the PI’s laboratory. Further details regarding specific roles and responsibilities will be elaborated in individual Award letters issued to selected projects.

PIs are generally expected to identify a student, postdoctoral fellow, or research associate who is fully familiar with the molecular and/or cellular assays needed to support the project. Selected projects will be supported for 6–24 months with critical go/no-go decision points defined for this project period. The specific level of support will vary by project need.

Deadline: 

All LOIs must be received by 5pm, October 22,2021. The most promising proposals will be selected for full proposal development.

Eligibility: 

All Stanford faculty with PI eligibility are welcome to apply.

Application Instructions: 

LOIs should be submitted as single PDF files containing the following materials in the order indicated below. All documents should 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, a project summary for a lay audience (150 words max).
2. Letter of Intent (3 pages maximum) –
   1. High-throughput Screening Assay Development: 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 (cells 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.
   3. Prototyping of Protein Therapeutics: Briefly describe the medical need the project seeks to address and the case for the biological target of the anticipated drug prototyping effort. Where relevant, briefly describe the structure and/or properties of the bioactive protein that serves as the starting point of your project. Briefly describe the biological assays that will be required to guide the optimization of the compound. Emphasize what is novel about your approach.
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 three 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-January 2022.