Tackling Parkinson’s Disease With Allosteric Modulators

Gain Therapeutics was founded by our current chairman, Dr. Khalid Islam, as a spin-out from a Spanish biotech company called Minoryx.

Minoryx had several promising early-stage drug candidates, but given its resources, it wasn’t clear whether they’d be able to advance efficiently. Since patent life keeps moving, there was a real opportunity to build a new company around these assets and the underlying drug discovery platform, which was originally called SEE-Tx^TM and is now known as Magellan.

Magellan integrates AI into its computational framework, and at the time, we were among the early adopters of AI in drug discovery. The company was built with the mission of addressing serious unmet medical needs, particularly in neurodegenerative and rare diseases. While many biotech companies start with broad ambitions, we’ve remained committed to these areas, focusing not just on symptoms but on the root biological mechanisms of disease.

Allosteric modulators are compounds that bind to a target protein or enzyme at a site away from its active site. In the case of our lead compound, GT-02287, the target is an enzyme called glucocerebrosidase – or GCase for short – which plays a central role in Parkinson’s disease biology. GCase is a “cellular maintenance facilitator”. It helps clear toxic substrates in the lysosome and supports mitochondrial health by aiding electron transport. When GCase fails, those systems begin to break down, and ultimately, so does the cell.

Traditional drugs often bind directly to an enzyme’s active site, usually to shut it down. But that can interfere with function or limit therapeutic potential. With an allosteric modulator, the goal is different – we restore protein function so it can work properly. GT-02287, for example, binds to GCase at an allosteric site, stabilizing the enzyme and preventing misfolding. Misfolding can happen because of genetic mutations, like GBA1, or through post-translational modifications. By stabilizing GCase, our molecule helps the enzyme fold correctly and move through its natural trafficking pathway in the cell.

This approach doesn’t just provide localized activity – it allows GCase to carry out all its essential maintenance roles throughout the cell before it’s eventually degraded.

That’s the advantage of drugging allosteric sites: instead of shutting proteins down, we can restore and enhance their natural function, which is a fundamentally different and – we believe – more effective therapeutic strategy.

Our initial thinking was that GT-02287 would be most effective in patients with a GBA1 mutation. GBA1 encodes the enzyme GCase and mutations in this gene increase the likelihood of GCase malfunction. Targeting that group seemed like the clearest path, since these patients have a higher probability of misfolded or dysfunctional GCase.

However, what really shifted our perspective came during our first-in-human study in 2024. In healthy volunteers – people without known GBA1 mutations – we saw a statistically significant increase in GCase activity after dosing with GT-02287. That finding suggested the drug could enhance GCase function even in individuals without a genetic defect. This raised an important question: could patients with idiopathic Parkinson’s disease, who don’t carry a GBA1 mutation, also benefit from increased GCase activity? We believe the answer is yes. Even modest improvements in GCase activity may help protect cellular health, clear toxic substrates, and slow disease progression.

That’s why our current Phase 1b study is enrolling both idiopathic and GBA1-mutated patients. We know these groups may respond differently. GBA1 patients often develop Parkinson’s earlier, with faster-moving and more severe symptoms, representing a smaller but high-need population – about 10–15% of Parkinson’s cases in the US. But Parkinson’s is a broad and heterogeneous disease, with multiple phenotypes and progression patterns. By including both groups, we’re aiming to understand how GT-02287 can make an impact across the full spectrum of the disease.

For a small biotech, pursuing a novel approach like allosteric therapeutics often brings a higher level of skepticism than it would inside a large pharmaceutical company. The reality is that most small biotech companies don’t succeed, so the burden is on us to generate a critical mass of data that convinces the outside world our science is both real and impactful. That’s been one of the biggest challenges – proving that our approach isn’t just interesting in theory, but transformative in practice.

Speaking personally, I hope we’re able to remain an independent company. Over the next 5–10 years, I’d like to see us continue advancing GT-02287 toward approval and patient access, while also building out a pipeline of earlier-stage candidates. That said, we recognize the complexity of drug development and remain open to thoughtful partnerships or selective licensing opportunities where they make strategic sense. The long-term vision is to grow – deliberately and sustainably – into a fully integrated biopharmaceutical company, much like Gilead, Amgen, or Biogen in their early years, with the goal of making a meaningful and lasting impact in neuroscience and beyond.