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Geroscience-based Chronic wound treatment product development


Fast- Track proposals will NOT be accepted. Phase II information is provided only for informational purposes to assist Phase I offerors with their long-term strategic planning. Direct-to-Phase II proposals will NOT be accepted. Number of anticipated awards: 1 to 2 Budget (total costs, per award): Phase I: $350,000 for 12 months; Phase II: $2,500,000 for 2 years It is strongly suggested that proposals adhere to the above budget amounts and project periods. Proposals with budgets exceeding the above amounts and project periods may not be funded. Summary: Ulcerative wounds, including venous leg ulcers, diabetic foot ulcers and pressure ulcers, occur more commonly in older adults and their impaired healing is associated with underlying and comorbid diseases of aging, and defects of wound repair. The incidence of chronic wounds, those that are difficult to heal or do not follow a normal healing process, increases with age from the sixth to the ninth decades. Chronic wounds rarely occur in persons without multiple chronic conditions, and specific comorbid conditions exacerbate them, notably malnutrition and metabolic syndrome. Delayed wound healing increases the risk of recurrent infection and tissue necrosis. This results in substantial morbidity, disability, hospitalization, and even mortality among older adults. Using just one clinical example, an older person with diabetes can develop a foot ulcer, it may progress and fail to heal, necessitate a foot or toe amputation, and ultimately increases the risk of death. Until recently, approaches to chronic wound treatment have been primarily mechanical barriers and frequent dressing changes, including skin substitutes (such as acellular dermal substitutes, cellular dermal substitutes, and cellular epidermal and dermal substitutes), medical devices, and care processes such as surgery. These products are not regulated based on demonstrating Page 99 effectiveness, and comparative studies have been rare without identified superior approaches. Recent advances in the understanding of the wound-healing process have led to innovative clinical approaches to wound care including the use of stem cells, growth factors and bioactive materials to support the body’s own regenerative capacity, but these approaches have not yet obtained regulatory clearance or approval by the Food and Drug Administration (FDA). Project goals: This initiative proposes to fund development of a new geroscience-based approach to treating chronic wounds. Novel gerosciencebased approaches may target relevant mechanisms of wound healing including stem cell therapies, cell senescence, inflammation, adaptation to stress, epigenetics, metabolism, macromolecular damage and/or proteostasis. Cellular senescence was initially described by Hayflick and Morehead in 1961, and more recent work has shown that senescent cells can negatively affect their local tissue environments through multiple pathways. The inflammatory response following tissue injury has important roles in both normal and pathological healing. Inflammatory cells, cytokines and growth factors all play key regulatory roles in the complex series of events during wound healing. Among potential inflammatory targets for wound healing therapeutics, the macrophage may be an attractive target, both in terms of reducing fibrosis and scarring, and to improve healing of chronic wounds. Vascular responses to stress may be adaptive in the wound healing process. Several epigenetic regulatory factors, such as the endogenous non-coding microRNAs, have been demonstrated to be drivers of the wound healing response. Metabolic considerations relevant to wound healing are also important and include the collagen metabolism requirements, and impairments from neuropathy and metabolic disruption in diabetes. The goal of this solicitation is to call for the development of a geroscience-based wound healing product which may include but are not limited to: cellular products and therapies, immune modulation, microbiome-modifying therapy, human tissue, animal-derived tissue, and biosynthetic products. The product would be developed for clinical application to chronic non-healing wounds, in conjunction with current standard therapies. Proposals should establish proof-of-concept for and/or support preclinical development of a candidate geroscience-based wound healing product, as well as standardize methods to evaluate wound healing and safety of the candidate product(s). Proposals that significantly advance a candidate product toward clinical development are highly encouraged. Offerors must outline in their proposal the preliminary data supporting selection of the geroscience-based product for wound healing, specific clinical question and unmet clinical need in the areas of chronic wound healing that their product will address. This RFA would solicit a Phase I project for a small business to advance development of their geroscience-based wound healing product. The activities could include pre-clinical development and feasibility testing in Phase I and might involve developing the design of a comparative clinical trial that might comprise a subsequent Phase II for treating older adults with chronic wounds to induce healing. Activities not responsive to announcement: Proposals that are limited to existing FDA approved or cleared therapies for wound healing or their equivalent (dressings, barriers, skin substitutes, etc.) would be considered non- responsive. Phase I Activities and Expected Deliverables: • Select one geroscience-based potential wound healing product (drug, cellular product or drug-device) and develop and test the prototype. • Show differentiation of this product relative to other wound care products in terms cost, ease of use, efficacy, side effects, etc. • Conduct non-clinical toxicology studies (e.g., sensitization, immunogenicity) (optional) • Complete adequately powered animal trial with appropriate wound-healing endpoints (as appropriate for stage of development) • Complete preparatory steps for human studies (as appropriate: e.g., finalize protocol, data and safety monitoring plan, obtain IRB approval). (if applicable) • Perform human usability studies for the prototype with at least 10 subjects (ideally, but not required) • Develop regulatory strategy/plan and timeline for seeking approval from FDA to conduct human trials or market the product (as appropriate). Phase II Activities and Expected Deliverables (Phase II information is provided only for informational purposes to assist Phase I offerors with their long-term strategic planning): • Conduct sterility and pharmaceutical testing • Perform in vitro studies of product release over time • Perform in vivo pharmacokinetic and biodistribution (PK /BD) studies Page 100 • Complete adequately powered human trial with appropriate wound-healing endpoints (ideally, but not required) • Complete preparatory steps for human studies (e.g., finalize protocol, data and safety monitoring plan, obtain IRB approval). • Develop commercialization plan that includes a go-to-market strategy and include comparable reimbursements, manufacturing, and distribution
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