The first in-class non-opioid drug for treating moderate, severe, and persistent pain with no addiction nor tolerance

Project Information

TAFALGIE

Grant agreement ID: 101145380

DOI

10.3030/101145380

EC signature date 14 February 2024

Start date 1 March 2024

End date 30 November 2026

Funded under

• The European Innovation Council (EIC)

Total cost

€ 17 388 832,00

EU contribution

€ 2 499 999,00

Coordinated by

TAFALGIE THERAPEUTICS
France

Periodic Reporting for period 1 - TAFALGIE (The first in-class non-opioid drug for treating moderate, severe, and persistent pain with no addiction nor tolerance)

Reporting period: 2024-03-01 to 2025-06-30

Summary of the context and overall objectives of the project

A spin-off company of the CNRS/IBDM, founded in 2020 in Marseille, France, Tafalgie Therapeutics aims to capitalize on more than 15 years of fundamental academic research dedicated to understanding the fundamental molecular and cellular mechanisms of acute and chronic pain. This work has led to the identification of a secreted endogenous protein called TAFA4 and a comprehensive understanding of the specifics of its completely new mechanism of action, both peripheral and spinal, in modulating the pain signal between sensory neurons and the central nervous system.
The company's ambition is to disrupt the market to offer patients who are underserved or poorly served a safe and effective non-opioid alternative in the coming years, thanks to drug candidates that act for the first time in the field of pain as a disease modifier. This is in line with the importance of societal issues related to the current pharmacopoeia for pain, which remains a public health challenge worldwide, in a unique market Momentum.
Pain is, in fact, the most common disease in the world. According to the World Health Organization (WHO), 1.5 billion people worldwide suffer from persistent pain. With the aging of the global population, the average global prevalence of chronic pain is expected to increase steadily. Opioids are powerful analgesics that are widely used. However, in the United States, opioid addiction is considered an “opioid epidemic”: more than 727,000 deaths between 1999 and 2022 and a reduction in life expectancy of 0.67 years in 2022.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Tafalgie Therapeutics entered the clinical phase in May 2025 with its first lead, a first-in-class compound selected from its large portfolio of patented TAFA4 peptide derivatives. To move from identifying a secreted endogenous protein to a drug candidate, the company had to focus primarily on optimizing the design and manufacturing of TAFA4 peptide derivatives. Tafalgie has undertaken development works in both solid-phase chemical synthesis and bioproduction with the aim of making them administrable intravenously, subcutaneously, and orally. This preliminary step in preparing for clinical trials to prove concept and translational efficacy has enabled the company to diversify its IP portfolio with four new patents. At the same time, the company continued its R&D work in close partnership with the IBDM and the CNRS, under several successive research collaboration agreements, focusing on understanding its mode of action and the signaling cascades. In this context, the company has established a team of 26 employees to operate a discovery platform, in particular to validate the analgesic efficacy of TAFA4 in comparison with that of opioids and to demonstrate its excellent safety profile.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

An alternative solution to opioids could potentially benefit millions of patients worldwide who are waiting for appropriate treatment without side effects, which could have a considerable impact on the medical, societal, and industrial levels.
The first step is for Tafalgie to prove that the very good preclinical results obtained will also be observed during clinical trials and that the proposed new-generation solution is comparable in terms of efficacy to existing solutions on the market today, with a significantly improved safety profile. This will require the implementation of a sequential, step-by-step clinical strategy, gradually expanding the target territories (especially Europe and the United States), the modes of administration, and the indications addressing acute and post-operative pain but also chronic pain. In line with this, the design of the next step clinical protocol (a phase 2A trial) is currently being finalized, with the aim of starting trials in H1 2026.
One of the key needs in ensuring the continued implementation and success of this strategic development plan is, of course, the company's ability to access financing. The company has secured €37 million in funding to date, including €30 million in capital, and it is already planning to supplement its fundraising with an additional round by the end of 2025.
To meet the challenge of developing a therapeutic offering easily accessible to the mass market and ensuring its rapid adoption by the entire healthcare ecosystem, it will also be necessary to secure the backing of a strategic industrial partner through a licensing contract. The objective is to manage international multicenter clinical trials, which are a prerequisite for obtaining a worldwide drug marketing authorization, and to pilot market access efficiently. This will also rely on optimizing R&D programs related to the bioproduction program to offer pricing in line with global market expectations.
As a Discovery Platform dedicated to the pain sector, Tafalgie Therapeutics will need to continue to invest in ongoing scientific research, and shall even expand it, with a high-level R&D team currently being strengthened, to consolidate its expertise in the field of pain, diversify its therapeutic targets and research programs, and strengthen the company's intellectual property portfolio.