IND-enabling studies on novel Cav3 T-channel modulators for treatment of neuropathic pain

7. PROJECT SUMMARY Neuropathic pain remains a poorly managed medical condition affecting more than 1.5 billion people worldwide. Over 20 million people suffered from diabetic neuropathy and neuropathic pain in the US alone in 2015. The current standard of care is insufficient. Topical applications and systemic treatment with existing analgesics, including opioids, leave millions suffering. More than 50% of these patients are refractory to medication. Opioids frequently cause devastating side effects, and overdose has claimed 300,000 lives in the United States since 2000. The lack of effective analgesics for chronic pain has contributed to the opioid crisis. To address this National Health Emergency, we at AfaSci Research Laboratories have discovered non-opioid new class of compounds to treat neuropathic pain with the SBIR Fast-Track grant support. Our compounds possess much greater potency and selectivity to modulate the T-type Cav3.2 channel than all currently known T-channel inhibitors. Rigorous in vivo pharmacokinetic and pharmacodynamic (PK/PD) studies and preliminary toxicological studies have provided valuable scientific insights that enabled AfaSci to select AFA-279, along with several backup candidates, for the IND-enabling studies proposed in this SBIR Phase IIB project. At their efficacious doses, our new compounds did not produce observable side-effects frequently experienced with existing pain therapeutics. We have conducted multiple tests comparing the effectiveness of these new compounds against a current neuropathic pain medication, gabapentin. Our compounds showed greater analgesic effects than gabapentin in multiple rodent neuropathic pain models. The goal of this proposed SBIR Phase IIB project is to submit the IND application on our Cav3.2 modulator to the Food and Drug Administration (FDA). To achieve this goal, three Specific Aims must be accomplished: 1) produce AFA-279 under Good Manufacturing Practice (GMP)-like conditions using chemical manufacturing controls (CMC) for GLP nonclinical toxicity studies and GMP clinical batch future Phase 1 clinical trials, 2) complete toxicological and safety studies under Good Laboratory Practice (GLP) to establish the safety profile of AFA-279 and 3) prepare and submit the IND application for our novel T-channel modulator to the FDA. Our investigative team (PI Dr. Xie, Chemist Dr. Kayser, Pharmacologist Dr. Zou, and Project Manager Dr. Greene) with consultants (Toxicologist Dr. Tepper and Statistician Dr. Yang), and our Scientific Advisors will collaborate with Stanford Medical School and contract research organizations (Regis Technologies, Charles River Laboratories and AnaBios) to ensure successful completion of this exciting project. Success in this project will lead to a successful FDA IND filing of our Cav3.2 modulator. We will then initiate early clinical trials on our novel T-channel modulator with our strategic partners, Cavion and/or Biohaven. Our ultimate goal is to deliver a safer, more effective, non-opioid Cav3.2 channel modulator to patients suffering from neuropathic pain and to help address the opioid epidemic by providing effective non-addictive analgesics.8. PROJECT NARRATIVE AfaSci has developed a non-opioid analgesic candidate AFA-279 for the treatment of neuropathic pain. With a novel mechanism of action, AFA-279 has the potential to be a more effective and safer analgesic drug than current pain medicines. SBIR program funding will help us successfully transition from preclinical to clinical drug development after proving it is a safe drug candidate through IND-enabling studies. In light of AfaSci’s strong track record in translational research to address the urgent opioid crisis, we believe this application merits strong consideration as a candidate worthy of support under this special SBIR Phase IIB program.