Allodynic Therapeutics, Inc. is a clinical-stage pharmaceutical company focused on developing naltrexone-acetaminophen combination for treating acute migraine and co-occurring anxiety. The company has completed four investigator-initiated clinical trials that have provided promising results in treating various pain conditions and is now launching a phase-2 clinical study for treating acute migraine. The naltrexone-acetaminophen combination US patents extend to 2037

Main Points:

1. Research indicates that both naltrexone and acetaminophen individually are effective in treating acute migraines, physical pain, and emotional pain (References 1-15).
2. In a clinical study, the naltrexone-acetaminophen combination demonstrated greater emotional pain relief compared to the sum of the individual components, suggesting a synergistic effect in the treatment of emotional pain.

Study 1: Acute Migraine factorial study involving 72 patients across five treatment groups. (Link to preprint)
Study 2: Acute Migraine study with 36 patients in three treatment groups.
Study 3: Nine-month Migraine Prevention study, included twelve patients in two treatment groups, with an extension phase for non-responders. (Link to preprint)
Study 4: Nine-month Chronic Low Back Pain study, involved twelve patients in two treatment groups, with an extension phase for non-responders.

Key Findings:

1. 1. Acute Migraine Factorial Study: Naltrexone 2.25 mg (n=19) demonstrated a 17.3% higher response rate for pain freedom at 2 hours compared to placebo (n=17) (Reference 14).
   2. Migraine Prevention Study: 67% of patients receiving twice daily naltrexone 2.25 mg-acetaminophen 325 mg (N=6) experienced a 75% reduction in migraine days, compared to 17% of placebo patients (N=6) (Reference 15).
   3. Nine-month Migraine Prevention and Chronic Low Back Pain Studies: ALLOD-2 showed a 50% higher response rate than placebo in achieving a ≥50% reduction in the Pittsburgh Insomnia Rating Scale-20 (References 14-15).

Key Achievements:

1. Investigator-initiated acute migraine studies: two studies involving 108 patients.
2. Migraine prevention study: nine-month duration.
3. Chronic low-back pain study: nine-month duration.
4. FDA Type B, face-to-face meeting held on July 21, 2019.
5. Initial Pediatric Study Plan accepted by the FDA.
6. FDA breakthrough designation for naltrexone-clonidine combination in 2013.
7. Two orphan drug designations.
8. Submission of five Clinical Study Reports to the FDA.

Key Points:

1. 1. The naltrexone-acetaminophen combination is protected by three U.S. patents (9,095,548, 9,707,225, and 11,058,68).
   2. The naltrexone-ibuprofen combination holds one patent (9,205,081).
   3. Market advantages include established public trust in acetaminophen and the use of “low dose” naltrexone.
   4. A potential for over-the-counter “Super Tylenol.”

Key Points:

1. Naltrexone (NTX) is thought to reduce pain by blocking the Toll-Like Receptor 4 (TLR4), which lowers pro-inflammatory cytokine levels associated with pain.
2. TLR4 is found in the Dorsal Root Ganglia (DRG) and trigeminal ganglion neurons.
3. Activation of TLR4 leads to pro-inflammatory cytokines (e.g., CGRP, TNF-Alpha, IL-1 Beta, NO, ROS) that cause neuropathic pain.
4. Naltrexone suppresses cytokine production, acting at the origin of the TLR4-activated cascade and preventing the production of multiple cytokines.
5. Individual cytokine blockers (CGRP and TNF-alpha inhibitors) act downstream from naltrexone, blocking only one of many neuropathic pain-generating cytokines.
6. Acetaminophen is believed to work by inhibiting cyclooxygenase-2 (COX-2), leading to reduced PGE2.
7. The naltrexone-acetaminophen combination targets multiple biological pathways, simultaneously reducing the production of pro-inflammatory cytokines and PGE-2.