Resources

Drug Discovery Roadmap

Target Discovery

Screening

Hit-to-Lead

Lead Optimization

Preclinical Development

Clinical Development

Drug Discovery at Michigan

From target discovery to clinical trials, many researchers and technology centers across the University of Michigan are involved in developing new therapeutics — including Michigan Medicine, the Rogel Cancer Center, the College of Pharmacy, the Life Sciences Institute, and the College of Literature, Science, and the Arts.

Expert guidance, cutting-edge technological resources, and funding are available to U-M investigators at every step along the path to innovation. This roadmap will help you find the key resources and criteria for every stage of the drug discovery process.

Target Discovery

“Our strength is our breadth,” says U-M President Mark Schlissel. U-M faculty, trainees, and staff have a centuries-long track record of novel discoveries to advance scientific knowledge and improve human health.

Science

Is there a clearly defined molecular target or phenotype that can potentially be modulated with drug-like compounds?

Are disease models and reagents available?

Is there a biomarker that can confirm target engagement?

Has the target been validated using chemical probes or genetic experiments?

Commercialization

What’s the current standard of care for this disease area — and does this project have the potential to “move the needle?”

What’s the potential commercial opportunity?

How do-able is the project?

What are the potential risks versus rewards?

How competitive is the project?

Funding

Basic research funding from federal agencies and foundations

Screening

High-throughput screening can rapidly identify drug-like compounds of interest for a specific molecular target, which are then confirmed and triaged to provide an investigator with a small number of promising results.

The U-M Center for Chemical Genomics provides high-throughput screening of diverse small molecule, natural product and siRNA libraries — along with assay development and optimization — for basic biology and drug discovery projects. The core also has a growing catalog of FDA-approved compounds for drug repurposing projects.

Science

Is the assay translational, relevant, robust, practical, and cost-effective?

Should the screening strategy include small molecules, natural products and/or a virtual screen?

How will hits need to be confirmed — what follow-up assays will be needed?

How will selectivity between similar targets be established?

Commercialization

What unmet medicinal need will your work address?

If successful, which and how many diseases will be treatable and how will your new treatment be superior to existing standard of care?

Funding

Funding from federal agencies and foundations

University seed funding

Hit to Lead

Moving from primary hits to the identification of a chemical lead is the least formulaic stage of the drug discovery process.

The goal is to develop data that charts a path forward — using medicinal chemistry, primary pharmacology, chemical informatics, and computational models.

Science

Are the compounds identified in the screen novel and “drug-like”?

Can the properties of screening hits be improved through the development of analogs?

What computational and/or structural methods can enable the project?

Commercialization

How likely is your project to result in new intellectual property (patents)?

What is the competitive landscape – what other compounds/programs are you aware of that are intended to address the same or a similar unmet need and how advanced are they?

Funding

Translational research funding from federal agencies and foundations

Early risk-sharing alliances with pharmaceutical and biotech companies

University seed and translational funding

Lead Optimization

The next challenge is in turning a promising lead into a preclinical drug candidate. Major investments are made in developing hundreds of analogs in an effort to obtain a molecule that is sufficiently potent, selective, bioavailable and safe for in vivo testing.

This is also when the business side of the commercialization process begins in earnest.

Science

What is the intended route of delivery in the clinic?

What improvements are required in potency, selectivity, ADME (absorption, distribution, metabolism and excretion), pharmacokinetics and safety?

What data are necessary for an in vivo proof-of-concept, i.e., an experimental demonstration that the compounds identified modulate the intended target in vivo (pharmacodynamics) and exhibit the expected biology (efficacy)?

Commercialization

What are the ideal and minimally acceptable profiles for a new therapy in this area, e.g., indication, patient population, mode of delivery, dosing regimen, efficacy, and safety?  (The Target Product Profile)

Who are the potential partners that may be interested in supporting/funding this project?

What are the most important scientific questions/risks and how can these be addressed early?

Funding

Funding from federal agencies and foundations

Alliance with pharmaceutical company, biotech or venture capital firm, or accelerator

University translational funding

Preclinical Development

To settle on a final drug candidate, key information about efficacy, metabolism, safety, and chemistry must be obtained to prove the compound’s bonafides. This is an iterative process; if one candidate fails, others may be tried.

Preparations are made to file Investigational New Drug application, known as an IND, with the Food and Drug Administration.

Science

A small number (typically 1-3) of high-quality compounds have been identified. How will these be prioritized based experimental assessments of safety, efficacy, cost-of-goods, ease of manufacture, and deliverability?

How will the top candidate (the development candidate) be prepared on scale and used to (a) assess preclinical safety and tolerability; and (b) develop an appropriate method for dosing people in the clinic (e.g., tablet, capsule, sterile liquid, etc.)?

What is the biomarker strategy for demonstrating proof-of-mechanism in the clinic?

Commercialization

What is the proposed clinical trial plan for assessing safety and efficacy in people?

What additional de-risking strategies can be employed to minimize risk to trial participants?

How will this product be differentiated from others already in the clinic?

What is the size of the intended market?

Funding

Federal small business innovation commercialization grants, known as SBIR grants

Alliance with pharmaceutical company, biotech or venture capital firm, or accelerator

Philanthropic “angel” funding

Translational research funding from federal agencies and foundations

Clinical Development

U-M provides support to research teams in their efforts to move discoveries from the bench to the bedside, including through the clinical trials necessary to bring new treatments and therapies to the public.

Science

What are the criteria for advancing or stopping development of this experimental drug?

How many patients will need to be treated to provide statistically meaningful results?

Will a placebo or current standard-of-care arm be included in the trial?

Commercialization

What evidence will be required to convince potential partners to support this project?

What level of risk/benefit profile will be acceptable to doctors/patients/payers?

How as the commercial landscape evolved?  Does the market opportunity still exist?

Funding

Phases I & II: Federal agencies and foundations

Phase III & IV: Primarily industry partners