CATALYST Special Notice ARPA-H-SN-24-114.pdf

Special Notice (SN) ARPA-H-SN-24-114 Proposers’ Day Announcement for Advanced Research Projects Agency for Health

(ARPA-H)/Health Science Futures (HSF) Office Opportunity: Computational ADME Tox AnaLYsis for Safer Therapeutics (CATALYST)

I. KEY INFORMATION

Table 1. Proposers’ Day Key Information Proposers’ Day October 29th, 2024, from 8:30 AM to 5:00 PM ET Location Cincinnati, OH (Hybrid) Website for registration https://solutions.arpa-h.gov/CATALYST Registration opens Friday, October 4th, 2024, at 10:00 AM ET Registration closes October 25th, 2024, at 12:00 PM ET for in-person attendance or when capacity is reached, whichever comes first. Virtual attendance will close 24 hours before the event starts.

Technical Point of Contact Dr. Andrew Kilianski, Program Manager, ARPA-H / HSF Office Program email CATALYST@arpa-h.gov Proposer deliverables, details below

1) Provide one (1) page slide for a 3-minute lighting talk

2) One (1) PDF page “teaming profile” (proposer’s capabilities, composition, research areas of interest, etc.)

II. INTRODUCTION

This Special Notice (SN) is intended to alert the scientific community to a newly approved ARPA- H Program and notify potential proposers of an associated Proposers’ Day (PD). Under the cognizance of HSF, ARPA-H intends to publish an Innovative Solutions Opening (ISO) for the CATALYST program no later than October 15th, 2024.

The Health Science Futures (HSF) Office of the Advanced Research Projects Agency for Health (ARPA-H) is sponsoring a Proposers’ Day (PD) for the planned proposer community in support of the Computational ADME Tox AnaLYsis for Safer Therapeutics (CATALYST) program.

Potential proposers are encouraged to attend the optional Proposers’ Day. While not mandatory, ARPA-H is hosting the CATALYST PD to achieve the following objectives:

• Draw attention of the scientific community to the CATALYST technical areas.

• Provide information about the program to potential proposers, including details about the overall program goals, solution summary, and full proposal structure for the forthcoming Innovative Solutions Opening (ISO), and how they might respond to ARPA- H’s forthcoming ISO.

https://solutions.arpa-h.gov/CATALYST mailto:CATALYST@ARPA-H.gov

• Share the intended scope, timeline, and scale of the CATALYST program and how the proposers, in collaboration with the ARPA-H team and resources, can accomplish the collective mission of accelerating equitable healthcare outcomes for all Americans.

• Initiate teaming arrangements among potential proposers to achieve program goals.

The PD will include brief overview presentations by government personnel; three (3)-minute lightning talks for potential proposers highlighting technical capabilities and promoting teaming arrangements; and five (5)-minute private sidebar meetings between the ARPA-H team and potential proposers. A limited number of sidebar meetings will be available to participants, and sidebar meetings must be scheduled via the registration website. ARPA-H will collect participant questions throughout the event and publish answers to a publicly available Frequently Asked Questions (FAQ) in https://arpa-h.gov/research-and-funding/programs/CATALYST/faqs.

Attendance at this event is not a requirement for submission of a solution summary, full proposal, or selection for funding; however, it is anticipated that unique multi-party teaming arrangements will be needed to successfully innovate and integrate the critical technologies necessary to meet the CATALYST program goals. Information relayed during the PD will be made available on the HSF Office section of the ARPA-H Opportunities page: https://arpa-h.gov/research-and-funding/programs/CATALYST as well as SAM.gov.

Advance Registration is required. Registration requests will only be accepted from the potential proposer community as participation is not intended for patients, patient advocates, media or a general interest audience.

III. CATALYST– PROGRAM INFORMATION

While full details of the CATALYST program will be provided in the forthcoming CATALYST ISO, the following is a brief description of the full program. Proposers should refer to the forthcoming CATALYST ISO for more details.

Overview The goal of the CATALYST program is to develop AI/ML-enabled in silico human physiology modeling platforms for ADME-Tox simulation to replace the poorly predictive investigational new drug (IND) IND-enabling preclinical animal studies currently used. Drug research and development (R&D) rely on in vivo animal model testing as a preliminary step towards FDA approval. However, the current IND-enabling preclinical animal study paradigm is often an imprecise model for human physiology, leading to an inefficient and expensive drug development process that does not accurately predict human drug safety outcomes. By leveraging innovation within the areas of large-scale data mining, AI/ML predictive analytics, novel high-throughput living systems instrumentation, and simulation-based whole human physiology modeling, CATALYST will create new tools to replace the current approaches that fail to fully recreate human physiology.

https://arpa-h.gov/research-and-funding/programs/CATALYST/faqs https://arpa-h.gov/research-and-funding/programs/CATALYST%20as%20well%20as%20SAM.gov https://arpa-h.gov/research-and-funding/programs/CATALYST%20as%20well%20as%20SAM.gov http://sam.gov/

CATALYST will develop qualified and validated in silico platforms for novel drug development, demonstrating their acceptability for assessing drug safety and creating a new “digital CRO” sector. The program will focus on Good digital eXperimentation Practice (GXP) pharmacokinetics (including absorption, distribution, metabolism, and excretion) and pharmacodynamics (safety and toxicity) that correlate with various human physiological states. To promote adoption of these platforms upon validation, CATALYST will concurrently fund product sponsors to integrate them into novel drug First in Human (FIH) approval packages. The teaming between the methodology developers and product sponsors is required for CATALYST to be impactful in the drug development industry. Eliminating the need for animal testing in preclinical studies will substantially reduce drug development costs, time, and resources that often prevent drugs with smaller markets from progressing. By providing a more accurate model of human physiological diversity, the in silico modeling platforms have the potential to provide a more reliable estimate of drug efficacy. Improved precision of predictions through CATALYST’s in silico platforms will result in increased success rates in human clinical trials, ultimately leading to faster, less expensive, and more effective drug development benefiting both patients and the broader healthcare ecosystem.

CATALYST will revolutionize current preclinical and clinical study practices with the following deliverables:

• AI/ML-enabled in silico human physiology modeling platforms for ADME-Tox simulation, that replace IND-enabling preclinical animal studies. The platforms will be adaptable to create fit-for-use in silico models of various major organ systems in the human body.

• Living system tools that generate new human data, and fill human data gaps, for the development of in silico platforms for ADME-Tox simulation.

• Independently verified in silico platforms using existing or new human clinical data and comparable validated assays.

• Demonstrated predictive capabilities of the in silico platforms through regulatory qualification of these platforms, and proof-of-concept FIH approvals based on data generated by these platforms.

Technical Approach CATALYST will create predictive modeling platforms for qualified drug safety applications by utilizing AI/ML modeling, supported by data capture in public and governmental spaces, and by developing novel methods to address data gaps and validate the platforms. The development of underlying technologies will facilitate the generation of human-relevant data, enabling the production of verifiable and comparable datasets. The program components include three technical areas (TA): data discovery methods and predictive drug safety models (TA1), living systems tools for model development (TA2), and in silico simulation-based human physiology models (TA3).

Technical Area 1 (TA1), Data discovery methods for predictive drug safety models

TA1 performers will capture and unify a wide range of existing preclinical, clinical, and electronic medical record (EMR) datasets that are available in the public and government domains, harmonize and curate these in a repository that can also integrate future datasets from the method development community, and produce a GXP environment and data governance platform to assure data quality and security. TA1 will procure foundation datasets for accurate deep learning methodologies to be developed within the team. The platform should also incorporate enhanced governance features for security, privacy and access control. The end result of this TA is the compilation of existing data into a framework that, either alone or with data gathered from TA2 and TA3, can be used to predict ADME-tox for a given drug.

Technical Area 2 (TA2), Living systems tools for model development TA2 will utilize both existing and emerging technologies, such as human and animal MPS, organoids, instrumented tissues, and ex vivo models to develop innovative tools that will generate datasets to inform the model development to occur in TA3. TA2 should be integrated with the other TAs that require data generation using novel methods for model development. TA2 technologies will result in novel data streams that understand, at fundamental levels, human physiology and its direct interaction with candidate pharmaceuticals.

Technical Area 3 (TA3), In silico human physiology models TA3 will utilize the datasets prepared and produced by TA1 and TA2 to generate and train generalized predictive platforms that are interpretable and explainable using various mathematical rules and AI algorithms and test the fidelity of the platforms using validated datasets (TA1 and TA2) and methods (TA2). Trained models should take multiple chemical, biochemical, and preclinical inputs and produce whole human predictive ADME-Tox modeling, including confidence metrics and other detailed outputs, needed for GXP validation and inclusion in IND submissions.

In addition to the identified TAs, the proposer teams for CATALYST should include a pharmaceutical product sponsor as an enabling element of the program. The Product Sponsor will implement the methodologies created in CATALYST Phase I to IND-enabling studies that will be performed in Phase II. Although the bulk of their work will be in Phase II, their inclusion in the team during Phase I will allow for the evaluation of Context of Use (COU) and other product specific requirements for the tools in creation.

Product Sponsor, Novel drug development activity The Product Sponsor will test the predictive platforms for specific COUs and provide feedback to refine TA1/2/3 for regulatory qualifications. As a drug developer, the Product Sponsor will utilize the platforms developed in Phase I of CATALYST in IND-enabling applications and regulatory submissions in Phase II.

Proposal Options Applicants may submit proposals for one of the following options:

Option A) A focused proposal targeting only TA1 Option B) A focused proposal targeting both TA2 and TA3 Option C) A comprehensive proposal addressing TA1, TA2, and TA3

The proposer teams for all options should include a Product Sponsor, as the proposer team’s ability to execute Phase I and Phase II will also be evaluated. Proposals addressing combination of TAs other than the specified options will not be reviewed.

Program Structure CATALYST is divided into two phases:

Phase I: Accelerated Technology Development and Method Qualification (36 months) – In Phase I, teams will focus on developing technologies that meet the in silico predictive goals of CATALYST. This will be through the pursuit of three technical areas (described in more detail below) led by teams built around the “Digital CRO” concept. At the end of Phase I, teams will submit their methodologies into novel drug development tool qualification pipelines that will facilitate their use in IND-enabling studies. Proposing teams must also include a Product Sponsor that will advise on COU and provide additional support to method development in Phase I. Upon successful Phase I completion, product sponsors will lead the adoption of these methodologies in Phase II, as described below;

Phase II: COU Concept Demonstration and Methodology Adoption – In Phase II, the team composition will shift towards Product Sponsor leadership, in which drug developers will pursue regulatory filings that include the in silico platform developed in Phase I in place of traditional, less predictive methods that rely on higher-order mammal experimentation.

CATALYST will support IND-enabling experiments to include the replacement of traditional methods and any additional data generation needed to support regulatory approval towards human clinical trials. Successful execution in Phase II of the program will demonstrate the potential of the in silico methodologies developed in Phase I and the reality of the “Digital CRO” concept supporting more accurate, cheaper, faster, and most importantly safer outcomes for clinical trial participants and users of licensed products.

IV. CATALYST – PROPOSERS’ DAY INFORMATION

Proposers’ Day Participation and Deliverables

This SN and PD include two specific opportunities for prospective proposers to identify team members:

Lightning Talks Interested attendees are invited to submit one (1) MS Power Point or Adobe PDF slide that summarizes their interests and capabilities. These will be presented to the entire PD audience during the lightning talk portion of the PD. Submitted presentations consisting of multiple slides or a single slide with multiple layers will not be granted a time slot. Lightning talk submissions (no more than one per organization) will be accepted on a first-come, first-served basis, until the maximum possible number of submissions (given time constraints) is reached. Interested attendees must identify their intention to submit the lightning talk during registration. Lightning talk submissions are restricted to those attending the meeting in-person.

Teaming Profiles Interested parties are also invited to submit a ‘teaming profile’ via the link here (https://solutions.arpa-h.gov/Teaming) and below. The teaming profile will describe the technical competencies, team capabilities, team composition, research areas of interest, unique facilities and other capabilities, as they relate to the program, and desired technical/other competencies sought from other potential team partners. The profile will include, at a minimum:

• Contact information, to include name, organization, email, telephone number, mailing address, and website

• Brief description of the proposer’s technical competencies and relevant facilities

• Desired technical competencies and facilities from other potential team members, if applicable

All teaming profiles must be submitted via the CATALYST Teaming Profile Form Link (https://solutions.arpa-h.gov/Teaming). The teaming profile will be updated regularly and made available on the program's teaming profile site (https://arpa-h.gov/research-and-funding/programs/CATALYST/teaming). Specific content, communications, networking, and team formation are the sole responsibility of participants. ARPA-H does not endorse any participating organization or exercise any responsibility for improper dissemination of the team profiles.

Live Q&A A live Q&A session will be led by the Business Innovation Division (BID) during CATALYST PD.

Virtual and in-person CATALYST PD participants are encouraged to use this time to discuss any CATALYST contracting questions you have with our contracting experts. ARPA-H will collect participants’ questions and BID responses and make them available in the Frequently Asked Questions (FAQ) in https://arpa-h.gov/research-and-funding/programs/CATALYST/faqs.

Registration Information Participants must register in advance through the registration website. Due to capacity limitation, in-person registration is limited to 150 participants. PLEASE NOTE: The registration cutoff date is October 25th, 2024, at 12:00 PM ET for in person attendance, or once attendance capacity is met, whichever comes first. Registration for virtual attendance will remain open until the day of the event. There is no registration fee for the CATALYST Proposers’ Day. Note that there will be no same-day registration. An online registration form and various other meeting details can be found at the registration website, https://solutions.arpa-h.gov/CATALYST.

Upon entry to a physical meeting, all attendees will be required to present valid, Government-issued photo identification. Individuals who are unable to register because the deadline has https://solutions.arpa-h.gov/Teaming https://solutions.arpa-h.gov/Teaming/ https://arpa-h.gov/research-and-funding/programs/CATALYST/teaming https://arpa-h.gov/research-and-funding/programs/CATALYST/teaming https://arpa-h.gov/research-and-funding/programs/CATALYST/faqs https://solutions.arpa-h.gov/CATALYST passed, or capacity has been reached for the PD or for the optional sidebar meetings, will be added to a waitlist. If slots remain open after registration closes or become available due to cancellations, the slots will be filled on a first-come, first-served basis from the waitlist.

All inquiries should be addressed to CATALYST@arpa-h.gov. Please refer to the CATALYST Proposers’ Day (ARPA-H-SN-24-114) in all correspondence. Prior to submitting an e-mail inquiry, please check the General Program FAQ’s (https://arpa-h.gov/research-and-funding/programs/CATALYST/faqs) to see if your question is answered there.

V. POINTS OF CONTACT

Technical Point of Contact Dr. Andrew Kilianski, Program Manager, ARPA-H / HSF Office

Email: CATALYST@arpa-h.gov All inquiries should reference “CATALYST Proposers’ Day (ARPA-H-SN-24-114)” in the subject line of the email.

VI. WEBINAR INFORMATION

Virtual attendees will receive the link to the webinar once they are verified and registration is confirmed.

VII. DISCLAIMER

This SN is issued solely for information and potential new program planning purposes; the SN does not constitute a formal solicitation for proposals or solution summaries. Responses to this notice are not offers and cannot be accepted by the Government to form a binding award.

Submission of any information in response to the SN is voluntary and is not required to propose to subsequent ARPA-H ISOs or research solicitations on this or any other topic. ARPA-H will not provide reimbursement for costs incurred in responding to this SN. Respondents are advised that ARPA-H is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted under this SN.

mailto:CATALYST@ARPA-H.gov https://arpa-h.gov/research-and-funding/programs/CATALYST/faqs https://arpa-h.gov/research-and-funding/programs/CATALYST/faqs mailto:CATALYST@ARPA-H.gov

Proposal Options