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National Center for Advancing Translational Sciences (NCATS)

Purpose

This Notice is being provided to inform potential solvers of the opportunity to compete in the NIH Oligonucleotide Toxicity (OligoTox) Open Data Challenge prize competition (https://ncats.nih.gov/funding/challenges).

The National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH), is announcing a Prize Challenge to incentivize the generation of high-quality and publicly accessible open datasets that can be used to advance predictive models for evaluating the toxicity of potential oligonucleotide therapeutics. The OligoTox Challenge is a two-phase prize competition that has the goal of creating publicly accessible, high-quality datasets from in vitro human-based systems that can lead to development of improved in silico models for predicting toxicity of an oligo based on its sequence, chemical modifications, etc.

NIH-NCATS intends to award a total prize purse of up to $500,000 across the two phases of the OligoTox Challenge. Additional information about the planned prize competitions is included below.

Potential applicants are strongly encouraged to contact NIH Program Staff at [email protected] to seek clarification on prize challenges.

Background

Oligonucleotides (“oligos”) are an emerging class of therapeutics most commonly used in the treatment of rare genetic diseases.  As used here, the term “oligos” refers to short (typically 15-30 nucleotides in length) nucleic acids intended to be used as therapeutics to treat human diseases by modulating gene expression.  Typically, oligo therapeutics contain chemical modifications in the phosphodiester backbone or sugar moiety to limit degradation by cellular nucleases.  Examples of therapeutic oligos include anti-sense oligos (ASOs), siRNAs, and microRNA mimics.  To date, there are 17 FDA-approved oligo therapeutics, and many more in clinical development, to treat rare genetic diseases, infectious diseases, and cancer.

As with any new molecular entity used as a therapeutic, the consideration of toxicity is a critical requirement in assessing safety. Toxicity in oligo therapeutics may be sequence-dependent (e.g., hybridization to nucleic acids other than the intended target) or sequence-independent (e.g., binding to cellular proteins) and are primarily assessed through expensive and time-consuming animal studies.  Notably, both the FDA (FDA Announces Plan to Phase Out Animal Testing Requirement for Monoclonal Antibodies and Other Drugs) and NIH (NIH to prioritize human-based research technologies | National Institutes of Health) are focusing on new approach methodologies that can reduce animal testing in preclinical safety studies through practices such as use of in vitro human-based systems, in silico/computational modeling, and other innovative platforms that can collectively evaluate immunogenicity, toxicity, and pharmacodynamics in humans and improve the predictive relevance of preclinical drug testing.  One possible strategy for assessing the toxicity of oligo therapeutics would be the use of in vitro human-based systems, including microphysiological systems (i.e., tissue chips, organs-on-a-chip) and 3-dimensional human organoids. NIH has already invested in both of these areas, and research is ongoing.

In recent years, we have witnessed dramatic increases in the use of advanced computational methods to address complex biological problems, such as AlphaFold for the accurate prediction of protein structures.  Advances in data science, such as through machine learning (ML) and artificial intelligence (AI), and in computing ecosystems, such as quantum computing, present an opportunity to develop in silico models to predict oligo toxicity. NCATS is holding this challenge competition to incentivize the development and release of publicly accessible open datasets that can be used train and test such models.

Eligibility

Participation in the OligoTox Challenge is open to individuals who are citizens or permanent residents of the United States, or private entities that are incorporated in or maintain a primary place of business in the United States. However, non-U.S. citizens and non-permanent residents can participate as a member of a team that otherwise satisfies the eligibility criteria. Non-U.S. citizens and non-permanent residents are not eligible to win a monetary prize (in whole or in part). Their participation as part of a winning team, if applicable, may be recognized when the results are announced. Full eligibility criteria will be available in the challenge announcement. For full details about eligibility requirements, competition rules, detailed judging criteria, and deadlines for submissions, please consult  https://ncats.nih.gov.

Prize Competition Details

The first phase (Ideation Phase) will focus on ideation by proposing data from in vitro human-based systems that can be collected and used in predicting the toxicity of a candidate oligo therapeutic. This in vitro human-based data may be supplemented by data from in vitro and in vivo animal models to improve predictive parameters and inferences.

The second phase (Data Generation Phase) will incentivize the collection, generation, and contribution of this data in creating a high-quality open dataset that can be released for public access for use in training and improving predictive models of oligo toxicity.  

The total prize purse for the OligoTox Challenge will be up to $500,000 across these two phases.

The entry submission window for the first phase of the OligoTox Challenge will be from December 19, 2025 – February 28, 2026 and for the second phase will be from May 1, 2026 –December 31, 2026. For more information, visit https://ncats.nih.gov/funding/challenges.

Pre-Submission Inquiries

A technical assistance webinar will be held for potential applicants for the OligoTox Challenge on  January 9, 2026, 12:00PM to 1:00PM Eastern Time. NIH staff will be available to answer questions related to the challenge.

If you are interested in registering to participate in the webinar, and/or submitting questions, please send an email to [email protected]. Webinar information will be provided upon request. Potential participants are encouraged to submit questions.

Webinar information will be available on the NCATS website at https://ncats.nih.gov. The slides and recorded webinar will be available approximately 7 days following the completion of the webinar. Participation in the webinar, although encouraged, is optional and is not required for the submission of an entry.

Inquiries

We strongly encourage interested parties to contact the NIH Program Lead listed below to discuss potential submissions at [email protected].

Sign language interpreting and real-time transcription services are available upon request to participate in this event.  Individuals who need interpreting services and/or other reasonable accommodations to participate in this event should contact Eric Sid ([email protected]; 301.827.3073).  Requests should be made five days in advance of the event. For Telecommunications Relay Service (TRS) call 711.

Inquiries

Please direct all inquiries to:

National Center for Advancing Translational Sciences
Email: [email protected]