Addex Therapeutics' GABAB PAM: A Breakthrough in Chronic Cough Treatment with Superior Safety and Efficacy

Chronic cough, a condition affecting millions worldwide, remains one of medicine's most frustrating unmet needs. With no FDA-approved therapies and existing treatments like baclofen and P2X3 inhibitors plagued by side effects, tolerance, and limited efficacy, patients and investors alike have long sought better options. Addex Therapeutics (NASDAQ: ADXN) may finally deliver it. The Swiss-based biotech is advancing a novel GABAB receptor positive allosteric modulator (PAM) that, based on preclinical data, offers transformative advantages over existing therapies. With IND-enabling studies imminent and a strategic pipeline, Addex is primed to capitalize on a $1.2 billion market by 2030. Here's why investors should take notice.

The Case for Therapeutic Superiority

Chronic cough patients face a stark reality: off-label baclofen causes sedation, respiratory suppression, and tolerance, while P2X3 inhibitors like gefapixant (Keflik) deliver modest symptom relief but with taste-related side effects that limit adherence. Addex's GABAB PAM, by contrast, appears to overcome these shortcomings in preclinical testing.

1. Efficacy Without Tolerance:
In guinea pig models, Addex's lead compound demonstrated dose-dependent reductions in cough frequency and latency to cough onset. Critically, subchronic studies showed no tolerance development—a major flaw of baclofen—maintaining efficacy at 1 mg/kg doses. This stability is critical for chronic therapies, where patients need consistent relief without escalating doses.

2. Better Safety Profile:
Non-GLP toxicity studies revealed a >30-fold safety margin, with biomarkers of tolerability unaffected even at 10x the effective dose. This wide therapeutic window contrasts sharply with baclofen's narrow margin and severe side effects. The PAM's allosteric mechanism selectively enhances GABA signaling, avoiding the non-specific activation that causes baclofen's CNS effects.

3. Superior to P2X3 Inhibitors:
In head-to-head trials against kefapixant (a P2X3 inhibitor), Addex's PAM matched efficacy while avoiding tolerance risks. Gefapixant's Phase 3 data, by comparison, showed only a 17.6% cough frequency reduction at 45 mg BID—below the minimal clinically important difference—and a 32% incidence of taste-related adverse events. Addex's candidate, if replicated in humans, could offer a cleaner profile.

Strategic Pipeline and Clinical Timeline

Addex's GABAB PAM isn't just a standalone asset; it's part of a broader platform. The same molecule is advancing in substance use disorder (SUD) through its partner Indivior, with IND-enabling studies completed in May 2025. This dual-track approach reduces risk: success in either indication validates the mechanism, while the SUD program's progress provides proof-of-concept momentum.

For chronic cough, the path forward is clear:
- IND-Enabling Studies: Commenced in June 2025, with clinical trials expected by early 2026.
- Market Differentiation: Once-daily oral dosing could outcompete gefapixant's twice-daily regimen and baclofen's short half-life.

The company's financial position supports this timeline. The $65 million raised via its Neurosterix spin-off in April 2024 provides ample runway, especially given its lean operations and focus on high-value programs.

Market Opportunity and Competitive Landscape

The chronic cough market is ripe for disruption. With 10% of the global population suffering from persistent cough and no approved therapies, Addex's candidate addresses a massive unmet need. Even a modest 10% market share would translate to over $120 million in annual sales.

Competitors like Merck (MRK) and AstraZeneca (AZN) are exploring P2X3 inhibitors, but their candidates face the same tolerability hurdles as gefapixant. Addex's PAM, with its dual therapeutic and safety profile, could carve out a leadership position.

Risks and Considerations

Preclinical success doesn't guarantee clinical victory. While the GABAB PAM's mechanism is well-validated in Indivior's SUD program, chronic cough trials will test its efficacy in humans. Additionally, regulatory scrutiny of new respiratory therapies remains high. Investors should also note that Addex's reliance on partnerships (e.g., Indivior) introduces execution risks.

Investment Thesis

Addex's GABAB PAM is a rare combination of innovation and practicality: a novel mechanism with clear advantages over existing therapies, a well-defined path to the clinic, and a market hungry for solutions. With a clean preclinical profile and a pipeline that leverages its platform across indications, Addex is positioned to deliver both near-term catalysts (IND submission by mid-2026) and long-term growth.

Recommendation: Buy ADXN with a price target of $12–$15 per share by 2026, contingent on positive Phase 1 data. Investors should monitor IND progress and preclinical data updates closely. For those seeking exposure to a high-risk, high-reward biotech with a potentially transformative product, Addex is a compelling play on an underserved market.

In a space where “better than nothing” has been the norm, Addex's GABAB PAM could finally mean “better than everything.”