Improving efficiency of low molecular weight radioligands for cancer therapy

OVERVIEW

Debiopharm, the Seeker for this Innocentive Challenge, is looking for novel broadly applicable approaches to reducing the renal reabsorption of low-molecular weight radioligands, in particular small-peptide radioligands or small-peptidomimetic radioligands, as a means of improving the efficiency and safety of these types of compounds in cancer therapy.

In recent years, low-molecular weight radioligands, e.g. small-peptide radioligands or small-peptidomimetic radioligands, have emerged as a promising approach to treat cancers that are characterized by overexpression of specific surface targets. Prostate cancer and neuroendocrine tumors are typical examples of this type of cancer.

However, such compounds face a major physiological hurdle: renal reabsorption. Due to their small size these radioligands are freely filtered through renal glomeruli and can be actively reabsorbed in renal cells, resulting in renal radiotoxicity and renal impairment, or even renal failure.

Current approaches to reducing the renal absorption of low-molecular weight radioligands, e.g. small-peptide radioligands or small-peptidomimetic radioligands, are insufficient; novel broadly applicable approaches are therefore needed. Finding such approaches is the objective of this Challenge.

Do you have any questions or need assistance? Feel free to join us in our Challenge Space! If you're interested in learning more about the Evaluators' requirements for this Challenge, we invite you to participate in our upcoming webinar.

Your IP Rights are protected in this Prize Challenge; Debiopharm must pay you an award to obtain them. The total prize award pool will be up to $40,000, and the best solutions have the opportunity to win an award between $2,500 and $20,000 for meeting the most important Solution Requirements.

The Challenge requires a written proposal to be submitted, and Awards will be contingent upon the theoretical evaluation of your proposal by Debiopharm against the Solution Requirements.

To receive an Award between $2,500 and $10,000, the Solvers are required to grant non-exclusive license rights to the Intellectual Property (IP) in their proposed solution.

To receive an Award between $10,000 and $20,000, the Solvers are required to grant exclusive ownership rights to the Intellectual Property (IP) in their proposed solution. Solvers will retain all rights to any not Awarded proposal.  

Submissions to this Challenge must be received by 11:59 PM (US Eastern Time) on February 2nd, 2026.

Please review the later Participation Guidance section before submitting a proposal.

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ABOUT THE SEEKER & ELIGIBILITY

Debiopharm is an independent biopharmaceutical company based in Switzerland with an ongoing commitment to develop tomorrow’s standard of care to cure cancer & infectious diseases and improve patient quality of life. Our main activities include drug development, drug manufacturing and digital health investment.

Employees of Debiopharm are ineligible to receive an award for this Challenge.

THE CHALLENGE

Background

In recent years, low-molecular weight radioligands, e.g., small-peptide radioligands or small-peptidomimetic radioligands, have emerged as a promising approach to treat cancers that are characterized by overexpression of specific surface targets. Prostate cancer and neuroendocrine tumors are typical examples of this type of cancer.

Low-molecular weight radioligands are composed of a small targeting ligand linked to a therapeutic radioisotope. This ligand specifically targets and binds to transmembrane receptors or antigens that are overexpressed on the surface of tumor cells. Following this binding, the radioisotope emits ionizing radiation (either alpha or beta particles) that kills the cancer cells.

Low-molecular weight radioligands generally consist of three parts:

1. The low-molecular weight targeting agent e.g., small peptide or small-peptidomimetic. An agent characterized by low molecular weight (<5 kDa), the ability to rapidly penetrate tumors, and fast clearance from the blood.
2. The radioisotope. Two specific radioactive isotopes are commonly used in low-molecular weight radioligands: beta-emitter Lutetium-177 (¹⁷⁷Lu) and alpha-emitter Actinium-225 (²²⁵Ac). Both are characterized by the high energy and very short range of the emitted particles.
3. The linker. The radioactive isotope is generally sequestered by a chelating agent (e.g., DOTA) that is connected to the low-molecular weight targeting ligand via some sort of linker, e.g., an alkyl chain, PEG, or a peptide-based linker.

Even though low-molecular weight radioligands, in particular small-peptide radioligands or small-peptidomimetic radioligands, show a lot of promise in terms of efficient tumor targeting, they still face a major hurdle: renal reabsorption. Due to their size, these radioligands are freely filtered through renal glomeruli and can be actively reabsorbed by renal cells.

Renal reabsorption varies but can exceed 90% of the filtered load. Such renal reabsorption can not only reduce drug availability for tumors, lowering the therapeutic index of a treatment, but can also result in renal radiotoxicity and renal impairment, or even renal failure. Overall, renal reabsorption poses significant constraints over low-molecular weight radioligand dosing in clinical setting, reducing patient outcomes.

Several broadly applicable approaches are known to reduce renal reabsorption of low-molecular weight radioligands – such as small-peptide radioligands and small-peptidomimetic radioligands – including:

• Co-administration of basic amino acids, Gelofusine (succinylated gelatin), or albumin-binding moieties.
• Conjugation of radioligands to albumin binding moieties.
• Incorporation of hydrophilic linkers.
• Removal of charged residues from small-peptide sequences.

However, the existing strategies have drawbacks, and there is a need to develop new strategies. Finding new approaches is the objective of this Challenge.

SOLUTION REQUIREMENTS

By posting this Challenge, we’re looking for novel broadly applicable approaches to reducing the renal reabsorption of low-molecular weight radioligands, particularly small-peptide radioligands or small-peptidomimetic radioligands, as a means of improving their efficacy for cancer therapy.

We explicitly welcome proposals that define transferable design rules or modular strategies expected to be applicable to a wide range of low-molecular weight radioligands, independent of tumor indication, molecular target, or radioisotope. While not required, submissions that also provide a concrete example of how the strategy could be applied to create an actual product will be particularly valued.

We envision that this can be achieved by following several directions:

• Chemical and molecular design approaches, such as systematic modulation of linker architecture, physicochemical properties, or amino-acid composition of small-peptide or peptidomimetic targeting agents,
• Generalizable target-interaction or receptor-engagement strategies, for example multivalent, bispecific, or alternative binding paradigms that can be applied across different targets without compromising tumor affinity.
• Platform-type formulation or conjugation strategies, including modular or reversible conjugation concepts that can be broadly implemented without dependence on a specific radioligand or radioisotope.

We’re open to any innovative proposal if it meets the following Solution Requirements:

1. It is a new and previously unconsidered approach to reducing renal reabsorption.
2. It is broadly applicable to a wide range of low-molecular weight radioligands (<5 kDa), especially a wide range of small peptide or small peptidomimetic radioligands.
3. It is compatible with all common chelating agents (such as DOTA and NODAGA) and all common radioisotopes (such as Lutetium-177 (¹⁷⁷Lu) and Actinium-225 (²²⁵Ac).
4. It would not be expected to reduce kidney reabsorption of the low-molecular weight radioligand at the expense of the tumor to kidney uptake ratio.

We will not accept solutions that:

• Are only applicable to biological carriers of >50 kDa in size, such as full-length antibodies.
• Necessitate alterations to targeting ligands that could be expected to substantially reduce tumor affinity.
• Rely on the use of non-bio-compatible materials, e.g., non-degradable nanomaterials.
• Could increase the molecular size of the low-molecular weight radioligand to an extent that renal clearance can be expected to be impeded.
• Focus solely on isotopic and dosimetric modifications without addressing renal reabsorption.
• Rely on speculative or unvalidated pathways.
• It can be expected to increase toxicity in other tissues, e.g., the liver.

Important! We are not interested in solutions that provide no more than a literature review on the topic.

The proposed solutions must be practical, that is, provide us with an actionable roadmap to build a low-molecular weight radioligand with increased capacity of minimizing the renal reabsorption following systemic (intravenous) injection. That means that every proposed idea must be solidly supported by mechanistic or molecular rationale and the available (and precisely referenced) literature/patent precedents. A discussion of any potential trade-offs, such as effects on binding affinity, target specificity, or radiochemical stability is a must. The preference will be given to proposals that are supported by the published pre-clinical and clinical studies.

Solutions with Technology Readiness Levels (TRLs) 1-3 are invited.

This Prize Challenge has the following features:

• Your IP Rights are protected; Debiopharm must pay you an award to obtain them.
• The total prize award pool will be up to $40,000, and the best solutions can win the award between $2,500 and $20,000 for meeting the most important Solution Requirements.
• The Challenge requires a written proposal to be submitted, and Awards will be contingent upon the theoretical evaluation of your proposal by Debiopharm against the Solution Requirements.
• To receive an Award between $2,500 and $10,000, the Solvers are required to grant non-exclusive license rights to the Intellectual Property (IP) in their proposed solution. To receive an Award between $10,000 and $20,000, the Solvers are required to grant exclusive ownership rights to the Intellectual Property (IP) in their proposed solution.
• Solvers will retain all rights to any not Awarded proposal. 
• Debiopharm may issue “Honourable Mention” recognitions for notable submissions that are not selected for monetary awards.
• Debiopharm may wish to partner with the Solver at the conclusion of the Challenge. Please indicate your interest in partnering.

YOUR SUBMISSION

Please log in and register your interest, to complete the submission form.

The submitted proposals must be written in English and can include:

1. Participation type – you will first be asked to inform us how you are participating in this challenge, as a Solver (Individual) or Solver (Organization)
2. Solution Level - the Technology Readiness Level (TRL) of your solution.
3. Partnering - there may be an opportunity to partner at the conclusion of this Challenge. Please indicate if partnering is of interest to you.
4. Problem & Opportunity - highlight the innovation in your approach to the Problem, its point of difference, and the specific advantages/benefits this brings (up to 500 words).
5. Solution Overview - detail the features of your solution and how they address the SOLUTION REQUIREMENTS (500 words, there is space to add more in the summary field, and attach supporting data, diagrams, etc.).
6. Solution Feasibility – Every idea must be solidly supported by mechanistic or molecular rationale and the available precisely referenced literature/patent precedents, that will help Debiopharm evaluate and validate the feasibility of the solution (up to 500 words).
7. Experience - Expertise, use cases and skills you or your organization have in relation to your proposed solution (up to 500 words).
8. Solution Risks - any potential trade-offs, such as effects on binding affinity, target specificity, or radiochemical stability is a must, any other risks you see with your solution and how you would plan for this (up to 500 words).
9. Timeline, capability and costs - describe what you think is required to deliver the solution, estimated time and cost (up to 500 words).
10. Online References - provide links to any publications, articles or press releases of relevance (up to 500 words).

PARTICIPATION GUIDANCE

1. Submission Close Date: Submissions to this Challenge must be received by 11:59 PM (US Eastern Time) on February 2nd, 2026.
2. Late submissions: Late submissions will not be considered.
3. Multiple submissions, 3 Maximum: In case of multiple submissions by the same Solver, only 3 submissions – the final 3 submitted – will be considered. Any other submissions will be deleted prior to evaluation.
4. Submission form and attachments: Your submission will be evaluated by the evaluation team first reviewing the information and content you have submitted at the submission form, with attachments used as additional context to your form submission. Submissions relying solely on attachments will receive less attention from the evaluation team.
5. Evaluation notification steps: After the Challenge submission close date, Debiopharm will review and select the winning ideas/solutions according to the timeline in the Challenge header. Everyone who submits a proposal will be notified about the status of their submissions.
6. Use of AI: Please note that any submissions produced solely with generative AI are not of interest.
7. Learn more: Find out more about participation in Innocentive Challenges.