NIH/NCI 466 - Novel Delivery Systems for RNA-based Cancer Vaccines

Fast-Track proposals will NOT be accepted.

Direct-to-Phase II proposals will be accepted.

Number of anticipated awards: 2-4

Budget (total costs, per award):

Phase I: up to $400,000 for up to 12 months

Phase II: up to $2,250,000 for up to 2 years

PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED.

Summary

The number of RNA-based cancer vaccines under development is rapidly expanding as genomic and predictive approaches reveal novel (neo)antigens capable of eliciting an immune response. While the rules for optimizing antigen selection are not yet fully understood, RNA-based vaccines can be generated quickly and have the flexibility to incorporate multiple (neo)antigens. These features make RNA-based vaccines ideally suited for rapid development and testing, as well as generating personalized cancer vaccines designed to elicit a tumor-specific response in an individual patient. While additional work is needed to demonstrate that RNA-based vaccines are safe and effective as anti-cancer agents, research in this field is evolving rapidly.

A critical step in developing an RNA-based vaccine is selecting an appropriate delivery system that can be produced at scale to generate clinical-grade material. Lipid nanoparticles (LNPs) are the most common delivery approach used to formulate RNA vaccines, but existing LNP platforms have significant technical liabilities. Many LNP delivery systems must be stored between −20°C and −70°C, owing to their poor stability. This creates logistical and cost challenges related to vaccine storage and distribution. Advancements are also needed in targeting specific cells or tissues, which may mitigate undesirable toxicity and inflammation. New delivery platforms are urgently needed to provide more options and better systems for early-stage vaccine developers who are designing novel RNA-based cancer vaccines. Further innovation is expected to accelerate the future clinical translation of RNA-based vaccines to treat human cancers.

Project Goals

The goal of this SBIR contract topic is to develop novel RNA delivery systems that will improve the safety, efficacy, and availability of RNA-based cancer vaccines. Offerors are invited to propose either novel LNP systems or other types of delivery approaches that can overcome the limitations of existing LNP delivery systems, as described above. Potential solutions include polymer-based approaches, dendrimer-drug conjugates, lipid nanoparticles, viral-like nanoparticles, and others. This solicitation invites proposals specifically focused on mRNA delivery, including mRNAs that harbor nucleoside modifications commonly used in vaccine design. Novel delivery systems that were previously evaluated using other types of therapeutic payloads may be proposed, but these systems must then be rigorously tested using mRNA payloads that mimic those suitable for generating RNA-based vaccines. This topic also encourages delivery systems that can target the primary tumor, metastatic sites, draining lymph nodes, or other cells/tissues that would improve the vaccine response.

Activities not responsive to this announcement:

Novel neoantigen prediction strategies and/or understanding how neoantigen selection impacts therapeutic response are not considered responsive under this topic. Strategies to optimize therapeutic response that do not involve RNA delivery (e.g., boosting strategies or combining multiple target antigens) are also not considered responsive under this topic.

Phase I Activities and Deliverables:

Design and generate a novel RNA delivery system suitable for formulating and delivering RNA-based vaccines for cancer indications.
Optional: Design and generate a targeted delivery system capable of localizing to a particular cell or tissue type and justify the rationale for the proposed targeting mechanism with respect to improving vaccine properties.
Demonstrate the loading capacity of the system using mRNAs mimicking those that would be used to generate RNA-based cancer vaccines (i.e., mRNAs harboring common nucleoside modifications).
Design and perform assays characterizing the performance of the delivery system as an RNA vaccine delivery vehicle (e.g., cellular uptake, mRNA release).
Define the appropriate analytical parameters to characterize the properties of the delivery system and develop analytical methods.
Perform studies to assess the feasibility of manufacturing scale-up that would enable batch sizes large enough to support Phase I/II clinical trials.

Phase II Activities and Deliverables:

Perform studies in an animal model demonstrating the capacity of the delivery system to deliver one or more mRNAs and elicit a high-agnitude T cell response against a cancer-relevant target antigen(s).
Optional: Establish a research collaboration with a group interested in developing a novel RNA-based cancer vaccine; utilize the delivery system to formulate a candidate vaccine and test this in a cancer animal model, monitoring the appropriate end points.
Design and perform studies in at least one animal model to benchmark the performance of the new delivery system against an LNP system that mimics and/or recapitulates one of the existing FDA-approved LNP systems.
- Note: The intellectual property landscape for existing LNP systems is complex. Offerors must explain in their proposal which LNP system(s) they will use for benchmarking studies, plans and timelines for obtaining these materials and securing any necessary licenses, and details on any consultants and/or organizations with whom they will collaborate to navigate these issues.
Demonstrate manufacturing scale-up that would enable batch sizes large enough to support Phase I/II clinical trials.
Validate analytical methods to characterize the delivery system with the necessary rigor to satisfy requirements of the US Food and Drug Administration (FDA).

Receipt date: Friday, October 18, 2024, 5:00 p.m. ET

Apply for this topic on the Contract Proposal Submission (eCPS) website.

View the full PHS2025-1 Contract Solicitation.