New Approaches to Avoiding Uptake of Lipid-Based Nanocarriers by the Liver

OVERVIEW

Debiopharm, the Seeker for this Wazoku Crowd Challenge, is looking for novel strategies to reduce the liver uptake of lipid-based nanocarriers (LNCs) carrying therapeutic drugs.

LNCs (liposomes and lipid nanoparticles) are increasingly used for systemic delivery of drugs, especially those that are poorly soluble in aqueous solutions.

Unfortunately, the use of LNCs to carry drugs to their desired destination suffers from a serious problem: their effective uptake by the liver. Available evidence shows that up to 90% of the LNCs carrying drugs are taken up by hepatocytes and Kupffer cells in the liver. As a result, the effective drug concentration in the blood decreases, so that only a limited amount of the drugs reaches the target organ or intended tissue.

Attempts to overcome this problem by specifically targeting drug delivery to other, non-liver, organs and tissues have been only marginally successful, if at all.

It's therefore becoming increasingly clear that the best approach to decrease the hepatic uptake of the LNCs carrying drugs is to “de-target” them from the liver.

The goal of this Challenge is to design approaches to prevent the LNC-formulated drugs from being taken up by the hepatocytes and Kupffer cells.

This is a Prize Challenge which requires a written proposal to be submitted. Awards will be contingent upon the theoretical evaluation of the proposal by Debiopharm. To receive an Award for this Prize Challenge, Solvers are required to assign exclusive rights to the Intellectual Property (IP) in their proposed solution. Debiopharm may also consider a non-exclusive transfer for a partial award if exclusive IP cannot be assigned by the Solver. Solvers will retain all rights to any proposal not Awarded.

Special WIN Scout referral opportunity

WIN Scouts are very much invited to participate, this being any Solver who can propose a potentially suitable partner (startup or expert) from your network. As a WIN Scout, by referring a relevant partner you will be recognized with a $10,000 recognition award if your referral results in a contract between the party referred and Debiopharm, signed within 2 years of your submission.

The input required is guided during the submission process for WIN Scouts below.

Submissions to this Challenge must be received by 11:59 PM (US Eastern Time) on September 10th, 2024.

- Login or register your interest to start solving and scouting!

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.
 

Wazoku welcomes WIN Scouts and referred partners to become active members of Wazoku Innovation Networks(WIN).

WIN Scouts are invited to participate in this Challenge, this being any Solver who can propose a potentially suitable partner from your network. By referring a relevant partner you could receive a $10,000 recognition award.

Find out more about participation in Wazoku Crowd Challenges.

THE CHALLENGE

Background

Lipid-based nanocarriers (LNCs)—liposomes and, more recently, lipid nanoparticles—are increasingly used for systemic delivery of drugs, especially those that are poorly soluble in aqueous solutions. LNCs also protect chemically unstable drugs from rapid degradation within human organs, tissues, and cells.

Unfortunately, using LNCs to carry drugs to their desired destination in the human body doesn’t solve the problem that plagues the delivery of many other therapeutic entities: their effective uptake by the liver.

In fact, available evidence shows that, depending on the individual drug and its dosage, up to 90% of the LNC-formulated drugs can be blocked in the sinusoids of the liver or taken up by hepatocytes and Kupffer cells. As a result, the effective drug concentration in the blood decreases, so that only a limited amount of the drug reaches the target organ or tissue.

To overcome this problem, attempts have been made to “re-route” the LNC-drug complexes from the liver by attaching to the LNC surface molecules—antibodies, proteins, peptides, etc.—that would target their delivery to other, non-liver, tissues and organs. Unfortunately, this approach has led to only limited success at best.

The best real-life example of this approach could be the HERMIONE, a randomized Phase 2 clinical trial, where liposomes carrying the anti-cancer drug doxorubicin and conjugated with anti-HER2 monoclonal antibody were evaluated for their efficacy against breast cancer. The study did not meet its primary endpoint and was terminated.    

It's becoming increasingly clear that the best approach to decreasing the hepatic uptake of the LNC-drug complexes would be to “de-target” them from the liver.

The goal of this Challenge is therefore to design approaches to prevent the LNC-formulated drugs from being taken up by the hepatocytes and Kupffer cells.

We envision that a strategy compatible with a systemic delivery (i.e., intravenous administration) can be designed allowing to dramatically decrease the liver uptake of the drugs complexed with a wide variety of LNCs, including lipid nanoparticles (LNP).

We also envision that the LNP-formulated drugs will include a broad range of possible therapeutic modalities: nucleic acids (DNA of up to 1 kb and RNA of up to 5 kb in size), peptides (ranging from 2 to 20 kDa), and small molecule entities (of up to 1 kDa, both water-soluble and water-insoluble).

We expect the proposed solutions in no way to interfere with the normal liver function, to be completely safe for humans at the therapeutically relevant doses, and, ideally, non-hemolytic and non-allergenic.

We expect the Solvers to not only outline their strategies but also provide a solid justification of their approaches. Any preclinical evidence of the lack of drug uptake by the liver, both in vitro and in vivo, will be especially appreciated.

SOLUTION REQUIREMENTS

We’re open to any innovative solution for as long as this solution meets the following Solution Requirements:

1. The proposed solution should be able to reduce the liver uptake of LNC-formulated drugs from 90% to 30% or less.
2. The proposed solution should be applicable at least to liposomes or lipid nanoparticles, and ideally to a wide range of lipid-based nanocarriers.
3. The proposed solution should be applicable to at least nucleic acids, and preferably to a wide range of therapeutic payloads, including peptides (ranging from 2 to 20 kDa), and small molecule entities (of up to 1 kDa, both water-soluble and water-insoluble).
4. The proposed solution should be fully compatible with the intravenous mode of drug administration.
5. The proposed solution must be fully compatible with human use and in no way interfere with the normal liver function at the therapeutically relevant doses.
6. The proposed solution should be compatible with the approaches to target other, non-liver, tissues and organs.
7. Ideally, the proposed solution will be non-hemolytic and non-allergenic.
8. Ideally, the proposed solution will be easy to scale for mass production.

At the same time, we want to reiterate that we’re not going to accept solutions that:

• Provide no pre-clinical experiments supporting the proposed strategy.
• Can in any way interfere with the normal liver function or be otherwise harmful to the human body.

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

This Prize Challenge, has the following features:

1. Your IP Rights are protected; Debiopharm must award you to obtain them.
2. The best solution has the opportunity to win the award of $40,000 USD for meeting all solution requirements, as solely determined by Debiopharm
3. The Challenge requires a written proposal to be submitted and awards will be contingent upon the theoretical evaluation of the proposal by Debiopharm against the Solution Requirements.
4. To receive an award for this Prize Challenge, Solvers are required to assign exclusive rights to the Intellectual Property (IP) in their proposed solution. Debiopharm is also willing to consider a non-exclusive transfer for a partial award if exclusive IP cannot be assigned by the Solver.
5. Solvers will retain all rights to any proposal not awarded.
6. WIN Scouts are invited to participate, this being any Solver who can propose a potentially suitable partner (startup or expert) from your network. As a WIN Scout, by referring a relevant partner you will be recognized with a $10,000 recognition award if your referral results in a contract between the party referred and Debiopharm signed within 2 years of your submission.The input required is guided during the submission process for WIN Scouts below.
7. Debiopharm may wish to partner with the Solver at the conclusion of the Challenge. Please indicate your interest in partnering. It should be clearly understood that Debiopharm is interested in partnering only with the Solvers who submitted a proposal, not with WIN Scouts. 

YOUR SUBMISSION

Please login 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), Solver (Organization) or WIN Scout – (submission uses an alternative form).
2. Solution Level - the Technology Readiness Level (TRL) of your solution.
3. 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).
4. 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.).
5. Solution Feasibility – Supporting Information and Rationale, such as references and precedents, that will help Debiopharm evaluate and validate the feasibility of the solution (up to 500 words).
6. Experience - Expertise, use cases and skills you or your organization have in relation to your proposed solution (up to 500 words).
7. Partnering - there may be an opportunity to partner at the conclusion of this Challenge. Please indicate if partnering is of interest to you.
8. Solution Risks - any 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).

Wazoku encourages the use by Solvers of AI approaches to help develop their submissions, though any produced solely with generative AI are not of interest.

Find out more about participation in Wazoku Crowd Challenges.

Submissions to this Challenge must be received by 11:59 PM (US Eastern Time) on September 10th, 2024

Late submissions will not be considered.

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.

After the Challenge submission due date, Debiopharm will complete the review process and make a decision with regards to the winning solution(s) according to the timeline in the Challenge header. All Solvers who submit a proposal will be notified about the status of their submissions.