Gain Therapeutics presents hopeful data for Parkinson’s, Gaucher treatment

By Jenni Spinner

- Last updated on GMT

(LPETTET/iStock via Getty Images Plus)
(LPETTET/iStock via Getty Images Plus)

Related tags neurodegenerative diseases Parkinson's disease Gaucher's disease preclinical development Data

The biotech firm has presented data from a study that could offer hope to patients with Parkinson’s, Gaucher, Alzheimer’s and other neurodegenerative conditions.

Gain Therapeutics, a biotechnology firm specializing in the discovery and development of therapies aimed at neurodegenerative conditions, recently presented data at a Michael J. Fox Foundation webinar. The data, emerging from a study conducted at the University of Maryland School of Medicine, involves evaluation of two lead structurally targeted allosteric regulators (STARs) compounds for treating Gaucher and GBA1 Parkinson’s disease; according to the company, the results showed “highly statistically significant effects” on all the tested phenotypes, signaling a potential breakthrough.

Eric Richman, CEO of Gain Therapeutics, took a moment to discuss the study with Outsourcing-Pharma, and to explain what the data might mean for Parkinson’s patients and their caregivers.

OSP: Could you please share an ‘elevator presentation’ description of Gain Therapeutics—who you are, what you do, key capabilities, and what sets you apart from other companies that could be considered competitors.

ER: Gain Therapeutics is a NASDAQ-listed biotechnology company that is developing small molecules to treat protein misfolding diseases. The company has a proprietary drug discovery platform called SEE-Tx, which uses a physics-based approach to discover novel allosteric sites on well-validated proteins. The output of the platform is novel small molecules that stabilize misfolded and dysfunctional proteins, addressing the root cause of disease.

Gain’s current pipeline of products has a focus on Lysosomal Storage Disease and CNS disorders, but the platform can be applied to any disease area wherein protein misfolding is implicated. The company signed a multi-target partnership with Zentalis Pharmaceuticals in oncology earlier this year and plans to continue expanding the pipeline to additional disease areas. Gain also has an additional partnership with Sumitomo Dainippon targeting a demyelinating disease.

The key difference between Gain’s approach and other small molecule companies is the power of the drug discovery platform. Powered by supercomputers, SEE-Tx is hyper-efficient and has a hit rate of 10% which is 100X more effective than traditional high-throughput screening methods.

Additionally, unlike AI methods, Gain’s platform uses the 3D structures of proteins and is not limited by training data. SEE-Tx uses molecular dynamic simulations, where water and organic solvents compete to interact with the protein surface. A patented method analyzes these results and provides quantitative druggability predictions based on changes in free binding energies. This method can induce the opening of hidden or "cryptic" binding sites, which requires a complex and specific coordination of ligand effects on the protein surface – this is unique and proprietary and allows Gain to discover and target previously undruggable sites on proteins.

OSP: Could you please tell us a little bit about the conditions at the center of your recent breakthrough, and why they’re especially worthy of novel treatments?

Eric Richman, CEO, Gain Therapeutics

ER: GBA Parkinson’s and Gaucher disease are both caused by mutations in the GBA1 gene which is responsible for the encoding of the lysosomal enzyme glucocerebrosidase (GCase). The homozygous form of the mutation is responsible for Gaucher disease, and the heterozygous form of the mutation is responsible for GBA Parkinson’s disease – which is estimated to include up to 14% of all patients suffering from Parkinson’s disease. There are currently no effective medical treatments for GBA1-related disorders. Current treatments are only symptomatic and do not alter the clinical course.

Parkinson’s Disease affects over 10m people worldwide – approximately 10% -14% of these have a GBA mutation. GBA mutations result in early onset, faster progression, and various non-motor symptoms due to accumulation of α-synuclein.

The data suggests that our compounds may have the ability to slow or stop the progression of disease in these patients and since the mutation is genetic, the population can be identified early in its course – potentially offering a treatment early on.

There are three types of Gaucher disease; Gain is focused on the neuronopathic forms of Gaucher (Types 2 and 3). There are approximately 1,000-2,000 patients with Neuronopathic Gaucher’s disease in the US and Europe. The disease is characterized by the buildup of glucosylceramide in the liver, spleen, bone marrow, and nervous system. T

There are severe neurological symptoms and the neuronopathic form is fatal, usually causing death before the age of 2.  The only treatment available today is Enzyme Replacement Therapy – a large molecule that does not cross the BBB and cannot treat the severe neuronal complications of this disease.  Our drug candidate is a small molecule that penetrates the brain and restores enzyme function offering a novel treatment for all types of Gaucher disease.

OSP: Ahead of your recent announcement at the Michael J. Fox Foundation event, could you please share an overview of any new treatments or candidates that have popped up to treat either of those in recent years?

There has been a considerable amount of research and development in the Parkinson’s space. To date, the MJFF has raised over $1b [USD]to help fund potential therapies and cures.

There are several therapeutic modalities targeting Parkinson’s and gene therapy is the second most common approach in the global development pipeline. However, there have been significant concerns with gene therapy in terms of safety, and even if approved it may not be suitable for all patients.

There have been significant advancements in small molecules, specifically in the area of pharmacological chaperones. Amicus Therapeutics developed a drug called Galafold (Migalastat), which is a pharmacological chaperone of alpha-galactosidase that is deficient in Fabry disease. The drug was approved by the FDA in August of 2018 for the treatment of Fabry disease and has validated the protein stabilization approach for misfolding diseases.

OSP: You mention in your announcement that this involves the “first small molecule approach to significantly reduce phosphorylated and aggregated -synuclein and increase GCase protein levels with transport to the lysosomes in iPSC dopaminergic neurons​.” Could you please share why this is important, potentially hopeful news for Parkinson’s and Gaucher patients?

ER: There have been several GCase targeted small molecule programs in development by large global pharmaceutical companies. These programs have shown initial positive results in increasing enzyme activity and levels, but these increases did not always translate to positive downstream effects.

Our data is promising because it shows the initial enzyme enhancement is resulting in improved trafficking to the lysosome and depletion of the toxic substrate. This is potentially hopeful news for PD patients because it would be an oral treatment that would be intervening in the early stages of disease with the potential to reverse the neurodegenerative effect seen in PD.

OSP: Can you tell us anything else about future steps for the candidates?

ER: An IND will be filed with the FDA for both the PD and Gaucher programs. An initial human study is planned for the second half of 2022.

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