Addex Therapeutics Ltd (SIX: ADXN) Q1 2025 Earnings: R&D Progress | June 20, 2025

This summary outlines the key points from Addex Therapeutics Ltd's Q1 2025 financial results conference call, presented by CEO Tim Dyer and Head of Translational Finance, Mikael Palinczeff (referred to as Misha).

Q1 2025 Highlights and Pipeline Update

Addex Therapeutics reported a "great start to the year" with several significant advancements across its pipeline, particularly in its allosteric modulator programs.

Key Achievements and Pipeline Progress:

• GABA-B Positive Allosteric Modulator (PAM) Program (Partnered with Indivior):
  • Indivior successfully completed IND-enabling studies for their selective drug candidate targeting substance use disorders. Addex is eligible for up to $330 million in milestone payments plus tiered royalties.
  • Addex independently selected a compound from this program to advance its chronic cough treatment. Preclinical profiling is substantially complete, and robust antitussive data has been published. IND-enabling studies are expected to start this year, subject to financing.
• mGluR2 Positive Allosteric Modulator (PAM) Program:
  • Addex regained rights to this program, including the Phase II asset ADX71149, from Johnson & Johnson. The company is evaluating new therapeutic indications for its development.
• mGluR5 Negative Allosteric Modulator (NAM) Program (Dipraglurant):
  • Dipraglurant is being repositioned for brain injury recovery (e.g., traumatic brain injury and stroke).
  • Addex secured an option agreement for an exclusive license to intellectual property covering the use of mGluR5 inhibitors in this indication.
  • Preclinical evidence suggests mGluR5 inhibition can facilitate adaptive rewiring of the brain, promoting neuroplasticity and functional recovery after stroke. Dipraglurant's differentiated profile (fast onset, short half-life, good tolerability) makes it suitable for use with rehabilitation.

Financial Results (Q1 2025)

Following the Neurosterics spin-out transaction, Addex's financials are now presented with continuing operations (retained business) and discontinued operations (divested business).

Key Financial Figures for Continuing Operations:

• Income: $0.1 million in Q1 2025, down from $0.2 million in Q1 2024, primarily due to the completion of the funded research phase with Indivior.
• R&D Expenses: $0.1 million, a decrease of $0.1 million from Q1 2024, also mainly due to the completion of the Indivior research phase.
• G&A Expenses: $0.5 million, a decrease of $0.3 million from Q1 2024, primarily due to reduced legal fees.
• Share of Net Loss of Associates: $0.8 million, related to the 20% equity interest in Neurosterics, accounted for using the equity method.
• Cash Position: Ended Q1 2025 with $2.8 million Swiss francs in cash, providing a cash runway through mid-2026. The cash burn has been significantly reduced. However, current cash does not fund the progression of unpartnered programs into the clinic.

Chronic Cough Program Details

Addex provided detailed preclinical data for its selected GABA-B PAM drug candidate for chronic cough (Compound A).

• Strong Rationale: Chronic cough has a large unmet medical need, with current treatments being ineffective or moderately effective for many patients and carrying significant side effects (e.g., taste-related issues with P2X3 inhibitors). GABA-B receptors are highly expressed in airways and neural pathways regulating cough, and Baclofen (a GABA-B agonist) is used off-label for cough.
• Preclinical Efficacy & Tolerability:
  • Compound A showed robust, dose-dependent antitussive efficacy, reducing cough by up to 70% in preclinical models.
  • It demonstrated a superior tolerability profile compared to reference drugs (nalbuphine, baclofen, codeine), with no significant respiratory depression or sedative-like effects at effective doses. This suggests a better therapeutic margin.
  • The compound maintained efficacy with chronic dosing and showed no signs of tolerance.
  • In head-to-head comparisons, Compound A showed better efficacy and potency than a P2X3 inhibitor with similar tolerability.
• Development Path: IND-enabling studies are planned for this year. The clinical development pathway is expected to include SAD/MAD studies in healthy volunteers, followed by a "challenge study" for early efficacy readout, and then a Phase II study in refractory chronic cough patients, potentially using advanced 24/7 cough monitoring technologies.

Post-Stroke Rehabilitation Program Details (Dipraglurant)

• Mechanism: mGluR5 receptors are involved in neuroplasticity and can contribute to "maladaptive rewiring" after stroke. Inhibiting mGluR5 can facilitate "adaptive rewiring," promoting recovery.
• Preclinical Evidence: Studies showed sustained improvement in sensory-motor function and stimulated brain connectivity in post-stroke rodents treated with mGluR5 NAMs.
• Suitability: Dipraglurant's fast onset, short half-life, and good tolerability make it ideal for use in tandem with rehabilitation therapies.
• Clinical Development Plan: Future studies will include clinical pharmacology to understand how to best modulate plasticity in healthy subjects and stroke patients, and to optimize dosing (e.g., before or after exercise) before moving to Phase II.