Addex Therapeutics: A Breakthrough in Brain Injury Recovery with mGlu5 Inhibitors?

The global biopharma landscape is abuzz with Addex Therapeutics’ (NASDAQ: ADXN) recent partnership with Sinntaxis AB to develop mGlu5 inhibitors for brain injury recovery. This exclusive license agreement, announced in April 2025, marks a critical step toward addressing one of medicine’s most pressing unmet needs: functional recovery after stroke or traumatic brain injury (TBI). Here’s why investors should pay close attention.

The Science Behind the Deal

The collaboration hinges on mGlu5 negative allosteric modulators (NAMs), a class of compounds that inhibit the metabotropic glutamate receptor subtype 5. This receptor plays a central role in neural plasticity—the brain’s ability to rewire itself after injury. A groundbreaking 2024 study in the journal Brain demonstrated that mGlu5 NAMs could reverse sensorimotor deficits and restore brain connectivity in rodent stroke models. Notably, treatment initiated even 10 days post-stroke showed efficacy, suggesting a broad therapeutic window.

Addex’s lead compound, dipraglurant, is an orally active mGlu5 NAM already tested in clinical trials for Parkinson’s disease. Its safety profile and receptor selectivity make it an ideal candidate for repurposing in stroke/TBI recovery. The Addex-Sinntaxis partnership will fast-track preclinical validation and design clinical plans to leverage these findings.

Deal Terms and Financial Implications

The agreement grants Addex an exclusive license to Sinntaxis’s intellectual property for mGlu5 NAMs in brain injury recovery. Key terms include:
- Upfront payment: An undisclosed option fee to Sinntaxis.
- Milestone payments: Up to $235 million tied to preclinical success, regulatory approvals, and commercialization.
- Royalties: 10-15% of net sales once the drug is on the market.

While Addex has yet to report milestone payouts (none were triggered in Q3 2023), the deal’s total potential value—up to $245 million—reflects confidence in dipraglurant’s prospects. The stock’s performance will likely hinge on near-term preclinical data and clinical trial initiation timelines.

Market Potential: A Multibillion-Dollar Opportunity

Stroke affects 12 million people annually, with 6 million deaths and widespread disability. Current treatments focus on acute interventions like thrombolysis, leaving post-acute recovery unaddressed. Similarly, TBI impacts millions globally, with no approved drugs for functional restoration.

The absence of pharmacological solutions creates a $1–2 billion annual market opportunity for therapies like dipraglurant. Addex’s drug could carve out a dominant share by targeting maladaptive plasticity—a mechanism that disrupts neural networks post-injury. Preclinical data showing additive benefits when combined with rehabilitative therapies (e.g., enriched environments) further strengthens its commercial appeal.

Risks and Challenges

• Clinical Trial Uncertainty: Preclinical success does not guarantee human outcomes. Addex faces the risk of efficacy failures or safety issues in Phase 1/2 trials.
• Competitor Landscape: While dipraglurant is first-in-class for stroke recovery, other mGlu5 NAMs (e.g., fenobam) are under development for neurodegenerative diseases.
• Regulatory Hurdles: Novel mechanisms and late-stage stroke/TBI indications may require innovative trial designs to secure FDA/EU approval.

Conclusion: A High-Reward, High-Risk Gamble

Addex’s partnership with Sinntaxis represents a bold move into a vast, underserved market. The scientific rationale is robust: preclinical data from Brain (2024) show dipraglurant’s ability to restore brain connectivity and functional recovery in stroke models. With no competing therapies targeting this mechanism, the drug could become a cornerstone of post-stroke care.

However, investors must weigh the risks. Success hinges on Addex’s ability to translate preclinical results into human trials and navigate regulatory pathways. If the drug reaches the market, the payoff could be transformative—addressing a $1–2 billion market with high unmet need. For now, the stock’s trajectory will depend on near-term milestones: preclinical data readouts in late 2025 and Phase 1 trial initiation by 2026.

In a sector where neuroscience innovation is scarce, Addex’s bet on mGlu5 inhibitors could redefine recovery for millions—making it a compelling, albeit risky, investment for biotech enthusiasts.