TAFALGIE THERAPEUTICS Announces First Dose Escalation Data From TAFAFIRST, a Phase 1 Clinical Trial Evaluating TT5, a first-in-class Non-Opioid Treatment For Pain

Marseille (France), July 10, 2025 – TAFALGIE THERAPEUTICS, a biopharmaceutical company specializing in the research and development of novel non-opioid pain treatments, today announces the first dose-escalation data from TAFAFIRST, a Phase 1 clinical trial evaluating TT5, its first peptide derivative of the endogenous protein TAFA4, in the treatment of pain.

Data collected on the first cohorts of healthy volunteers in the Single Ascending Dose (SAD) phase of the study demonstrated an excellent safety profile, and pharmacokinetics in line with expectations. Besides, they demonstrated favorable tolerability, without any side effect reminiscent of opioid analgesics (sedation, respiratory depression, etc.) observed. The data collected will also be used to determine the choice of doses for the second part of TAFAFIRST (MAD, multiple ascending dose). Finally, a third part will evaluate the analgesic efficacy of TT5 in patients. As of now, plasma concentrations higher than those expected to be clinically effective have been measured in healthy volunteers.

The TAFAFIRST single-center, ascending-dose, then repeated-dose, randomized, double-blind, placebo-controlled study is designed to assess the safety, acceptability, and pharmacokinetics of TT5, as well as early signals of analgesic efficacy in the treatment of pain. The launch of TAFAFIRST follows the green light given by the Australian health authorities to evaluate TT5, the first peptide derivative of the endogenous TAFA4 protein. This is the first me that a TAFA4 derivative tested in human clinical trials.

TT5 is the most advanced drug candidate in the TAFALGIE THERAPEUTICS porVolio. A non-opioid pain-relieving peptide with a novel mechanism of action, it is designed to be administered by intravenous infusion. Its development results from the discovery of the analgesic effects of TAFA4, a protein secreted in humans, whose function is to reduce the intensitý of the pain signal following tissue damage.

Its method of action, fundamentally different from that of current painkillers, meets the definition of what the Anglo-Saxons call a “Disease Modifier”: in other words, a molecule whose activity consists not only in modulating information, but also in triggering a cascade of events to restore normal cellular functioning.

TAFA4 affects specifically the two components behind post-injury pain:

• At the level of peripheral nervous fibers, by triggering a hitherto undescribed cascade of cellular signaling that reduces their activity exacerbated by the lesion.
• At the spinal level, by restoring the excitation/inhibition balance, two phenomena that modulate the level of intensity of the painful message to the brain.

TAFALGIE THERAPEUTICS plans to finalize the TAFAFIRST study at the end of 2025-beginning of 2026, followed by the launch of phase 2 clinical trials.

Today, one third of the global pain treatment market is covered by opioids, with an immediate risk of sedation, respiratory and digestive disorders, and a high medium-term risk of addiction, overdose, and death. A major public health issue, the global pain market is estimated at over 70 billion euros.