Small Molecule Therapeutics

The Stanford Innovative Medicines Accelerator (IMA) is accepting proposals for projects that address two major challenges in small molecule drug discovery: adaptation of laboratory-grade assays to high-throughput screening (HTS) formats to identify starting points for medicinal chemistry and optimization of lead compounds into drug prototypes.

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. Through this request for proposals, the IMA is soliciting Letters of Intent (LOIs) for projects to enter the HTS and the Medicinal Chemistry module of the IMA. Basic research, including target identification, is outside the scope of the current LOI solicitation.

Aim and scope:

• High-throughput screening: The IMA aims to partner with PI labs to enable the development, optimization, and miniaturization of a biochemical or a cell-based assay in 384- or 1536-well microplate format to screen against the HTSKC’s +200,000-member small molecule library. Projects with a strong structural biology rationale (experimental or AlphaFold) or using a ligand-based approach, but limited to low-throughput assays, will be considered for a virtual screen.
• Small molecule drug prototyping: Engineering of one or more small molecule leads to improve potency, selectivity, pharmacokinetics and/or pharmacodynamics with the goal of identifying a high-quality, patentable drug prototype. Projects with one or more small molecule leads (or series) as starting points for medicinal chemistry are encouraged to apply. Projects that have successfully completed HTS campaigns are eligible to enter the IMA small molecule prototyping program.

Competitive projects require 1) A strong therapeutic hypothesis that addresses a poorly met medical need, 2) A novel biological target or mode-of-action that is well-differentiated from other ongoing translational programs in academia or the biopharma industry, 3) Reproducible in vitro assays and/or animal models to guide small molecule drug prototyping. The goal of each project is to validate the therapeutic hypothesis underpinning the scientific discovery while generating intellectual property around the drug prototype that emerges from this work.

Support provided:

• High-throughput screening: Selected projects receive access to the Sarafan ChEM-H/ Chemical and System Biology High-Throughput Screening Knowledge Center (HTSKC). Support will include access to HTS compound libraries, virtual screening capabilities, instrumentation fees, associated consumables, expert training, and advice in assay development for high-throughput screening projects.
• Small molecule drug prototyping: Selected projects receive access to the Sarafan 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.
• Preclinical pharmacology: Support through the IMA’s Preclinical Pharmacology module can include the bolstering of in vitro assays and establishment of appropriate existing animal models.
• External resources: Depending on the nature and requirements of each project, the IMA can provide access to strategic alliances and vetted contract research organizations (CROs).
• Project management: IMA module leads in HTS, Preclinical Pharmacology and Medicinal chemistry will collaboratively help the PI formulate a goal- and milestone-driven project plan. In addition, the IMA Project Management team will support the project in planning, budgeting, and identifying outsourcing opportunities.

The IMA will generally not provide salary support for members of the PI’s lab.  The PI-lab is expected to contribute the equivalent of one full-time FTE to the project. Awarded projects can be supported for 12–18 months, according to a predefined project plan with critical milestones and go/no-go decision points. Details regarding specific roles, responsibilities, and financial allocations will be elaborated in individual award letters issued to selected projects. The specific level of support will vary by project needs.

Collaboration:

It is generally expected that the projects are run in a collaborative and fully transparent manner including decision-making processes, data generation and handling, experimental design, and external collaborations or resources. The IMA will act in a fully confidential manner and guarantee long-term data storage and accessibility.

Deadline:

All LOIs must be received by 5 PM PDT on Friday, June 28th, 2024. The most promising proposals will be selected for full proposal development.

Eligibility:

All Stanford faculty with PI status are eligible to apply. The support of the IMA is limited to one active project per PI at a time. However, PIs with an active IMA collaboration can be listed as a co-PI.

Application instructions:

LOIs should be submitted as a single PDF file 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
   • PIs name, co-authors names, department, address, phone number, email address
   • Project summary for a lay audience (150 words max).
2. Letter of intent (3 pages maximum):
   • Description of the poorly met medical need the project seeks to address.
   • The case for the biological target of the anticipated drug prototyping effort.
   • Information relevant to the structure and/or properties of the molecular target that serves as the starting point for drug development (if available)
   • Description of the intention of your project and the final goal.
   • Description of the biological assays that will be required to optimize and validate the therapeutic prototype.
   • Briefly describe the researchers in your lab who will support this project and the role(s) that they will play.
   • Elaborate the novelty of the proposed approach, highlight potential competitors in academia and industry, and patent landscape.
3. NIH-format biosketch for all investigators.

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:

Each LOI will undergo a three-step due diligence process.

 

1. The most meritorious LOIs will be identified based on:
   • Novelty of the therapeutic hypothesis and biochemical approach
   • Significance of the unmet medical need
   • Feasibility of support with the available technologies and resources at the IMA
2. PIs whose project ideas are selected will be invited to submit full proposals in collaboration with senior staff members of the IMA. The full proposal will cover the following points:
   • Description of envisioned mechanism of action
   • Strategy and steps towards the generation and/or development of the therapeutic prototype, including milestones, timelines, and go/no-go decision points.
   • Biological context and description of previous work performed on the therapeutic target.
   • Detailed description of in vitro assays and in vivo models needed for optimization and proof of concept studies.
   • Profile of the optimal therapeutic prototype (target product profile)
   • List of available and/or to-be-generated tool molecules and cell lines.
   • Publication, intellectual property, and exit strategy.
3. Mutual due diligence meetings between the IMA and PI to address any outstanding questions or concerns.