DARPA is soliciting innovative proposals that will generate anesthetics that can be used safely in cases of traumatic injury without physiological collapse. The envisioned approach will represent a paradigm shift, moving away from the administration of anesthetics with intense monitoring by highly-trained personnel to operational settings where such capabilities do not exist or cannot be afforded. A successful proposal will pursue the discovery of unappreciated anesthetic mechanisms, achieve anesthesia leveraging novel drugs or drugs as components of cocktails, and produce a formulated end product that exhibits increased safety compared to state-of-the-art drugs.
The program will comprise two sequential phases – Phase 1 (Base) will run for 36 months, with an optional Phase 2 of 24 months contingent on a successful go/no-go demonstration at the end pf Phase 1.
Technical Area 1: Discovery
- uncover novel targets and mechanisms that are involved in- and contribute to- anesthesia, and to validate those targets.
- advance the current understanding of molecular, neurological, and/or physiological mechanisms by which anesthetics work in order to leverage their beneficial effects as well as avoid negative effects. Proposed work to accomplish these goals can include top-down (complex biological models and phenotypic endpoints) and/or bottom-up approaches (reconstructing molecular pathway information, structure-guided drug discovery, etc)
Technical Area 2: Medicinal Chemistry
- design chemical compounds that specifically work through the targets and mechanisms of anesthesia identified in TA1 in order to achieve a safer anesthetic state.
- identification of initial compound hits for anesthetic mechanisms that are discovered and validated in TA1. Multiple approaches are available for initial design and discovery of novel compounds against a given target. This could involve single-drug single target, single-drug multiple-targets, or multiple drugs interacting with multiple targets to accomplish the desired physiological effects of unconsciousness, immobility, analgesia, amnesia, etc.
Proposals must address both technical areas across both phases.
Specifically excluded are proposals that involve:
1. Establishing new biological models for trauma or related indications.
2. Sole reliance on reformulation and/or clinical development of existing drugs.
3. Exclusive focus on the development of devices or equipment intended to optimize drug delivery or monitoring.
4. Development of drugs solely with analgesic properties (i.e., the novel drug or cocktail component does not act as a hypnotic or sedative).
5. Neurostimulation or electrical stimulation modalities intended to be therapeutic (e.g., nerve stimulation, deep brain stimulation, transdermal/transcranial stimulation, etc.).
6. Use of local anesthetics or nerve block in phase 2 of the program.
7. End products that utilize genetic engineering strategies.
8. Research that generates incremental improvements to the existing state of anesthesia drug development.
Closing on 21 August 2023
Broad Area Announcement: HR001123S0038