Translational Therapeutics Accelerator

Overview

The Problem

Drug development has several phases that are categorized as discovery (preclinical), development (clinical trials), and commercialization, once approved by regulatory agencies such as the U.S. Food and Drug Administration. For many reasons, the transition from discoveries in the academic environment to drugs entering the pipelines of pharmaceutical companies is often a place where significant opportunities for innovative therapies are lost – frequently referred to as the drug development “valley of death.”

How Can a TRxA Grant Help Academic Researchers

The Solution

TRxA leverages C-Path’s proficiency in translational and regulatory science to bridge the drug development “valley of death” by providing academic researchers with funding and guidance for the advancement of novel therapeutics from the lab to clinical trials and, ultimately, commercialization and patient care.

The Impact

TRxA operates as a not-for-profit drug accelerator providing the following for academic researchers who have applied for and received a grant award:

• Resources and hands-on guidance, working closely with academic researchers to develop comprehensive data packages for potential drug candidates, a key to garnering interest from biotechnology and pharmaceutical companies to invest in clinical trials.
• Tactical and strategic drug discovery and development leadership, including regulatory science considerations, bringing diverse expertise to pivotal early-stage academic study designs and implementation.
• Engagement of contract research organizations (CRO) to perform critical discovery phase experiments (e.g., key toxicology and other specialized studies) and/or validate academic studies to develop the type of comprehensive data package pharmaceutical companies require when licensing drug products.

To learn more about TRxA, be informed when the award application period opens, and how to apply for an award, contact us at TRxA@c-path.org or subscribe to our updates here.

TRxA is made possible by a grant from the Research Corporation Technologies, Inc’s Frederick Gardner Cottrell Foundation.

Funding Opportunities

About TRxA BRIDGe Awards

TRxA’s focus is translating early-stage novel therapeutics into Investigational New Drug (IND) supporting data packages that garner interest for licensing opportunities; we are helping “BRIDGe” (Breakthrough Research and Innovation in Drug Development Grants) the drug development valley of death. Projects eligible for TRxA BRIDGe funding and support include early lead optimization through IND-enabling studies of small molecule therapeutics. Biologics, including natural peptides or antibodies, cell and gene therapy applications, and diagnostic and medical devices are not eligible at this time; nor are drug repurposing initiatives.

TRxA funding and support is reserved for faculty at universities and non-profit institutions, anywhere around the world. Awards are not limited to specific therapeutic indications. TRxA offers funding and support for three (3) types of translational projects, ranging from early lead optimization to IND-enabling studies.

_{*Stage 3 proposals require pre-consultation with TRxA prior to submission}

Funds awarded through BRIDGe are provided for the purpose of carrying out research studies directly related to the project as documented in the approved research plan (either at the institution or through a contract research organization). Principle Investigators are required to concisely outline and justify direct project costs during the application process. Indirect costs are capped at 10%.

How to Apply for BRIDGe Funding and Support

To be eligible for BRIDGe funding and support, investigators need to hold a faculty appointment at a university or non-profit research institution, and intellectual property (IP) associated directly to the project cannot yet have been out-licensed.

TRxA accepts applications during its annual Request for Proposals, which will be announced in January of each year on this website and via email to those who have subscribed to TRxA news and updates.

To submit a pre-proposal application in response to the annual RFP, click here to access TRxA’s grants portal. More information about the application process is available in TRxA’s Guidance Document for Applicants. A User’s Guide for the grants portal is available here. The pre-submission consultation form is available here.

It is also recommended that principal investigators (PIs) coordinate with their university’s tech transfer and/or grants and contracts office in advance of applying to 1) make them aware of plans to submit an application and 2) provide an opportunity for review of the TRxA award agreement template to ensure the terms of a TRxA award are, in principle, acceptable.

During the application process, the TRxA team is available to meet with PIs via teleconference to answer any questions about requirements or the award process. These 30-minute consultations can be requested via email to TRxA@c-path.org.

Project Criteria

Stage 1

Entry criteria

1. Project is in early drug lead optimization.
2. Tractable drug leads from multiple chemical series have been identified (demonstration of optimizable structure-activity-relationships [SAR]).
3. Established in vitro pharmacology assays (biochemical and cell-based potency and selectivity).
4. Access to an available or conceived in vivo pharmacodynamic model.

Success criteria

1. Well defined compound progression pathway with established criteria.
2. .Optimized leads from multiple series (demonstration of optimizable SAR)
   • Characterized in vitro pharmacology properties including cell-based activity
   • Characterized absorption, distribution, metabolism, and excretion (ADME) properties (in vitro and rodent in vivo)
   • Demonstrated in vivo pharmacology in pharmacodynamic model
3. Access to an available or conceived in vivo efficacy model.

Stage 2

Entry criteria

1. Well defined compound progression pathway with established success criteria.
2. Optimized leads from multiple series (demonstration of optimizable SAR).
   • Characterized in vitro pharmacology properties including cellular activity
   • Characterized ADME properties (in vitro and rodent in vivo)
   • Demonstrated in vivo pharmacology in pharmacodynamic model
3. Access to an available or conceived in vivo efficacy model.

Success criteria

1. Defined target product profile (TPP) and vetted regulatory plan to achieve the TPP.
2. .Optimized molecule meeting candidate selection success criteria.
   • Characterized in vitro and in vivo pharmacology properties including demonstrated efficacy in in vivo efficacy model
   • Characterized ADME properties (in vitro and rodent/non-rodent in vivo)
   • Characterized Toxicology properties (in vitro and rodent/non-rodent in vivo)
   • Defined nonclinical formulation
3. Defined active pharmaceutical ingredient (API) scale up and characterization plan.

Stage 3

Entry criteria

1. Defined target product profile (TPP).
2. Optimized molecule meeting candidate selection success criteria.
   • Characterized in vitro and in vivo pharmacology properties including demonstrated efficacy in in vivo efficacy model
   • Characterized ADME properties (in vitro and rodent/non-rodent in vivo)
   • Characterized Toxicology properties (in vitro and rodent/non-rodent in vivo)
   • Defined nonclinical formulation
3. Defined good manufacturing practices (GMP) API scale up and characterization plan.

Success criteria

1. Adherence to the TPP and regulatory plan (or modifying it as needed).
2. Well characterized molecule with completed toxicology package to enable FIH (first-in-human) study.
   • General toxicology
   • Safety pharmacology
   • Genetic toxicology
3. Optimized API scale up strategy.

Need Additional Information?

To learn more about TRxA, be informed of when the award application period opens, and how to apply for an award, contact us at TRxA@c-path.org or subscribe to our updates. PIs are also encouraged to review the FAQ section of this website for additional details about the program.

TRxA is made possible by a grant from Research Corporation Technologies, Inc’s Frederick Gardner Cottrell Foundation.

Awarded Projects

Establishing a pleiotropic brain-penetrant small-molecule to impede glioblastoma

Project Summary:

Glioblastoma (GBM) is a highly invasive brain neoplasia with a median patient survival of 12-15 months from initial diagnosis. The highly refractory and heterogenous nature of GBM is primarily attributed to the large population of glioma stem cells (GSC) which exhibit remarkable plasticity and drug-resistance. Hence, till date, all repurposed kinase inhibitors exhibiting blood-brain-barrier penetrance failed glioma clinical trials. Loss of key tumor suppressors like PTEN and NF1 coupled to oncogenic activation of receptor tyrosine kinase PDGFRA and lipid kinase PI3KCA drive proliferation and invasiveness in GBM. Furthermore,the WNT-β-catenin signaling pathway maintains glioma stem plasticity through transcriptional upregulation of MYC, SNAIL, SOX2, NANOG. Hence, a successful therapeutic strategy will require pleiotropic targeting of diverse signaling pathways in glioma which promote proliferation and plasticity. As such, over the last 2 years, our international team has embarked on a medicinal chemistry project, screened over 250 molecules, and discovered ablood-brain-barrier penetrant, first-in-class PI3KCA/PDGFRA/WNT pathway inhibitor with a goal to start clinical development by 2026-27 for glioma therapeutics. DYR726 has been benchmarked against multiple kinase inhibitors currently in glioma clinical trials and exhibits asuperior in vitro biological profile in targeting a panel of primary patient-derived adult and pediatric glioma cells and 3D GSCs. Importantly, DYR726 exhibits a therapeutic index of 10-fold between GSCs and normal neurons suggesting potential glioma specificity. Although kinase inhibitors have not been successful in targeting glioma in the clinic, the pleiotropic nature of DYR726 may provide an effective therapy for patients diagnosed with glioma.

FAQs

Who We Fund

Who is eligible for TRxA funding?

Faculty at universities and nonprofit institutions, anywhere around the world.

Are there any institutional requirements?

Funding is available for projects at academic or non-profit organizations anywhere around the globe.

Are there any institutional commitments required, if funded?

Institution will be expected to engage with TRxA and negotiate a reasonable project agreement commensurate with the funding provided. A template of this agreement is available here.

What We Fund

Do you have criteria for small molecule? Is peptidomimetic allowed?

Peptidomimetics would qualify for funding, but the molecular weight should be less than around 1000 Dalton.

Do you fund only therapeutic projects or diagnostics projects as well? Diagnostics tools and instruments?

Funding is limited to small molecule therapeutics at this time. Diagnostics tools and instruments are outside of TRxA’s scope.

I have a small molecular drug. I know the target protein but do not know the binding site. I have the phenotype in vitro and mouse models. And I don’t have a family of compounds . Is this project appropriate for TRxA?

This would be considered a very early-stage application and could be considered depending on target and indication priority, but will likely be less competitive than projects with demonstrated Structure-Activity-Relationship (SAR) around their compound.

If we have a druggable target but not the actual drug, would that study not qualify?

Correct, we have targeted projects to support with identified chemical matter with some information around Structure-Activity-Relationship (SAR).

Would you consider siRNA as a small molecule therapeutic?

Not in the current round of funding, but please check back in the future.

Does TRxA fund gene therapies? What about repurposed drugs?

At this time TRxA awards are reserved for small molecule approaches. Gene therapies and drug repurposing are currently out of scope.

How TRxA Funding Works

What levels of funding are available through TRxA?

There are three funding levels for TRxA projects. IDC is limited to 10%.
Stage 1: up to $250,000 for one year (total costs)
Stage 2: up to $500,000 for one year (total cost)
Stage 3: up to $1,000,000 for one year (total cost)

If we apply for Stage 1, is the project still eligible to later apply for Stage 2 or 3 as the project progresses?

Yes, we envision that a successful project could progress down the pipeline. In these cases, it would be possible to advance to the next level funding outside of the established RFP timetable.

Does TRxA funding come to my lab?

Funds are awarded to the project, not necessarily the PIs laboratory – this may mean that part of the funds, or perhaps even all of them, go to CROs to help execute the project. This, combined with the support TRxA provides to define the Target Product Profile (TPP), the Product Development Plan (PDP) and associated regulatory strategies, will make your project more valuable for potential future licensing deals, and move towards the clinic.

What are allowable costs?

Those associated with executing defined project tasks, such as procuring assay specific lab supplies, animals, or core services. Salary support is only allowed if associated with a specific task in the project’s plan.
What’s not allowed? – General laboratory expenses, travel, equipment, tuition, or IP protection. IDCs are capped at 10%.

Do I need to worry about overlap with other funding sources?

No; in fact, it may be beneficial as the project will likely need more than just TRxA funds to get to the clinic, and availability of other funds will be a positive attribute.

If an SME would like to fund one aspect of an academic project, will TRxA be open to funding another aspect of the development?

Yes, we understand that TRxA funding will not provide all of the funding for the work required to file IND and we would welcome other funders contributing to compile the package of data necessary.

Application and Review Process

How many calls for proposals does TRxA conduct each year?

Currently TRxA accepts applications once per year.

How many projects do you fund?

Depending on the Stage of projects, we anticipate funding 3-7 projects per year, in the coming years. We hope to grow our available resources to increase the number of projects we can support.

Will you guide applicants on what stage they should apply for (e.g., how to proceed if research is somewhere between stage 1 and 2)?

Prior to submission of an application, you can schedule a time to speak with the TRxA team to gain consensus on the appropriate funding level. To schedule a teleconference, email your request and specific questions to TRxA@c-path.org.

Can our Tech Transfer Office (TTO) apply on behalf of the investigators?

Yes, but TRxA would be funding the project, so PI interaction is essential.

What does TRxA get out of this?

Terms and conditions in the project agreement will include a request for a percentage of income to the institution, when the project is successfully out-licensed, but we do not claim IP ownership. A template of the TRxA project agreement is available here.

Engagement of Contract Research Organizations (CROs)

How do I deal with CROs?

TRxA will help identify suitable CROs to do (part of) the work and will manage their contracts and payment directly. These costs will be subtracted from the budget available to your laboratory.

Do you help to find CRO/CDMO globally? Then do you join the management?

Yes, TRxA will help identify suitable CRO/CDMO and may directly contract the work. TRxA has no geographic restrictions and can contract with CRO/CDMOs that can provide the required service without limitations. Management of the external work will be handled jointly between TRxA and the PI.

IP

Is it required that IP protection be in place for chemical matter at the time of application in order to be considered for TRxA funding?

It is not a requirement that the technology has IP protection in place at the time of application, rather that the chemical matter may be eligible for protection (i.e., it is not disclosed in advance of any established priority date). Ideally, the PI will discuss a prosecution strategy with their University’s Tech Transfer Office (TTO) to advance the project to a stage that an identified licensee will assume the significant costs of national filings within 30-months of priority for an application filed under the Patent Cooperation treaty (PCT). To clarify, TRxA does expect that IP will be filed under PCT, not just in the US or North America, that may lead to patent rights in other national jurisdictions.

If an academic PI has launched a startup company and has the license for the IP, can the PI work with TRxA?

Once the project is licensed to a startup entity it would no longer be eligible for TRxA funding.

How to Contact TRxA

How does a PI reach out to you. Is this through the website?

You can reach the TRxA team at TRxA@c-path.org

Team

C-Path TRxA Team

Scientific Advisory Committee

Programmatic Review Board

_{TRxA is made possible by a grant from Research Corporation Technologies, Inc’s Frederick Gardner Cottrell Foundation.}