NIH/NCI 469 - Development of Novel Therapeutics for HPV-related Precancer

Fast-Track proposals will be accepted.

Direct-to-Phase II proposals will be accepted.

Number of anticipated awards: 3-5

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

There is no effective medical therapy for the millions of men and women who are infected with human papillomavirus (HPV). HPV can result in cancers at several organ sites (e.g., cervical, anogenital, and oropharyngeal). The lack of approved non-surgical approaches for the treatment of HPV-related precancer is a significant unmet medical need. Current strategies for persistent HPV infections with no clinically actionable disease include periodic follow-up for viral clearance, which is burdensome, and can cause patients anxiety and stigmatization. If HPV-related cervical preneoplasia is present, current standard of care includes surgical excisional or ablative approaches that are associated with higher risk of preterm delivery, chronic pelvic and perineal pain, and anogenital disfigurement and morbidity, and require highly trained providers. Additionally, current strategies for HPV-related anal cancer include ablative and surgical approaches that have high morbidity, and there are no identifiable precancerous lesions to intervene for oropharyngeal cancers. Furthermore, these strategies are challenging to scale up in lower resource settings due to lack of trained providers. Thus, novel systemic or topical/local approaches that intercept the progression of chronic HPV infection to precancer and/or induce regression of precancerous lesions can expand current therapeutic approaches and provide a precision prevention approach for HPV-related cancers before tumors develop.

Project Goals

The long-term goal of the work to be supported by this initiative is to prevent HPV-related cancers at relevant organ sites (e.g., cervical, anogenital, oropharyngeal) by bringing to the market novel, effective HPV therapeutics that can treat chronic HPV infections and/or cause regression of precancers. HPV therapeutics would also complement the primary prevention strategy of HPV vaccination and HPV-based screening for secondary prevention. The availability of simplified, effective treatments that do not require a clinician-based intervention would substantially accelerate control of cervical cancer and other HPV-related diseases. Such approaches, since they would target viral-specific molecular targets, may yield treatments with favorable safety and effectiveness profiles. Thus, these agents could potentially be applied broadly with much less concern about overtreatment leading to side effects, such as the possibility of pre-term delivery associated with excisional and, to a lesser extent, ablative treatments of the cervix. Ultimately, effective treatments would be particularly relevant in low- and middle-income countries (LMICs), where HPV screen-and-treatment programs rely on (over)treating most or all HPV-positive women because of lack of diagnostic (colposcopy and pathology) services and because they do not have the required human capacity to treat chronic HPV infection and precancers using these more traditional methods of excision or ablation. These novel treatments would also minimize the burden to some populations (e.g., rural communities) in accessing the healthcare system of high-income countries and could be used to treat people with chronic HPV infection without actionable precancer, who are still at an elevated risk of developing cancer.

This topic will solicit proposals focused on development of systemic, topical/local, or other novel intervention delivery approaches for treatment of chronic HPV infection and/or HPV-related precancers at relevant anatomic sites (e.g., cervix, anal/anogenital, oropharynx). This topic will solicit proposals that advance the development of both direct-acting agents (e.g., anti-viral) as well as agents that generate a strong anti-viral host response (e.g., vaccines). The work supported by this
topic will allow the translation of discoveries made in the laboratory into novel approaches for the prevention and interception of HPV-related cancers that could advance to first-in-human studies. Agents in the preclinical drug development pipeline (i.e., proof-of-concept, secondary testing, advanced preclinical development) will be considered for support.

Activities not responsive to this announcement:

HPV therapeutics that primarily target invasive cancer are outside the scope of this solicitation.

Phase I Activities and Deliverables:

Demonstrate in vitro efficacy for the agent in appropriate models.
Conduct structure-activity relationship (SAR) studies, medicinal chemistry for small molecules, protein engineering for biologics, and/or lead biologic optimization (as appropriate).
Perform preliminary animal toxicology and pharmacology studies as appropriate for the agent selected forbdevelopment.
Perform non-clinical efficacy studies in an appropriate model.
Develop a detailed experimental plan necessary for filing a pre-IND submission to the FDA.
Offerors should provide a justification and rationale for their choice of experimental model(s) for the proof-of-concept studies.

Phase II Activities and Deliverables:

Phase II projects should focus on product development and complete IND-enabling preclinical studies per the plan developed in Phase I. The scope of work may include further work on:

Perform animal pharmacokinetic and pharmacodynamic studies to optimize dosing regimen.
Characterization of immune responses to immunomodulatory agents.
Preclinical IND-enabling GLP toxicology studies.
Optimization of the formulation to achieve desired absorption, distribution, metabolism, and excretion.
Scale up cGMP production.
Develop a comprehensive regulatory strategy to encompass early-phase clinical trials.
Perform other IND-enabling studies.
Design and conduct early-phase clinical trials to assess the safety, tolerability, and early efficacy via phase 0 (microdosing), phase I (dose-finding), and phase II (preliminary efficacy) clinical trials.
- Optional: Offerors may consider clinical trials in partnership with NCI-funded clinical trial networks.

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.