Gain Therapeutics: Tackling Rare Diseases at the Genetic Level

Gene therapy continues to gain momentum as a promising approach for treating genetic disorders. The global gene therapy market is projected to grow from $3.8 billion in 2022 to over $13 billion by 2028, according to Reports and Data. With over 10,000 known monogenic diseases - illnesses caused by mutations in a single gene - the need for effective gene-targeting therapies is substantial.

Gain Therapeutics (GANX) is an emerging biotech that leverages a novel computational drug discovery technology to find new therapies for rare protein misfolding diseases caused by genetic mutations. The company aims to address the underlying structural causes rather than just symptoms.

Targeting the root cause of diseases

Many rare but devastating genetic disorders arise when specific proteins misfold into the wrong shape due to genetic mutations. These misfolded proteins disrupt normal cellular function and cause damage. Diseases like Gaucher, Parkinson's, Alzheimer's, and ALS fall into this category.

Current treatments only temporarily relieve symptoms; they don't address the root cause—the misshapen proteins driving disease progression. Patients experience debilitating health declines as misfolded proteins inflict destruction.

Gain's therapies bring hope by directly targeting misfolded proteins expressed by mutated genes. The company engineers small molecule compounds that bind twisted enzymes and proteins to correct their shape and restore their function.

"Straightening misfolded proteins could significantly slow or stop disease progression," said Dr. Manolo Bellotto, Gain's Chief Strategy Officer. "This could give patients years more healthy life."

For Gaucher disease, misfolded enzymes cause dangerous fatty deposits. In preclinical studies, Gain's lead therapy GT-02287 refolded the enzyme, reducing deposits by over 50%—addressing the root cause versus just managing symptoms. This first-of-its-kind approach could transform treatment for many rare conditions if proven successful.

Promising data on lead candidate

Recent data demonstrates Gain’s lead therapy, GT-02287, has significant potential. At the International Congress of Parkinson's Disease and Movement Disorders® in August 2023, Gain presented preclinical results showing GT-02287 improved Parkinson's symptoms and biomarkers by refolding misfolded proteins.

In a mouse model of Parkinson's, GT-02287 reduced neuroinflammation, neuronal death, and aggregations of alpha-synuclein proteins implicated in the disease. It also increases dopamine levels and motor function. Notably, GT-02287 decreased plasma NfL, an emerging neurodegeneration biomarker.

These compelling data provide early validation of Gain’s approach. By straightening essential misfolded proteins, GT-02287 could modify the course of Parkinson's and slow progression. Based on the extensive preclinical data generated with GT-02287, this drug candidate may also have application in the treatment of dementia with Lewy bodies and Alzheimer’s disease.

Gain plans to initiate Phase 1 clinical trials evaluating GT-02287 for Parkinson's disease in 2023. It would be the first treatment to target protein misfolding underpinning the disease if successful.

Focus on conditions with high unmet needs

Gain is pursuing treatments for several other devastating rare conditions that involve misfolded proteins wreaking havoc in the brain and other organs. These include GM1 gangliosidosis, Krabbe disease, and Alpha1 Antitrypsin deficiency.

The unmet need in these areas is massive. Parkinson's alone affects over 1 million people in the U.S., while Alzheimer's impacts over 6 million Americans. The emotional and financial toll on patients and families dealing with the disabling symptoms is immense.

At best, current treatments for these diseases only temporarily relieve some symptoms. They do nothing to slow the inevitable progression of the condition. Parkinson's patients struggle with worsening motor problems, while those with Alzheimer's experience steadily declining memory and cognitive function.

Gain's approach offers hope by targeting the misfolded proteins at the core of these diseases. For example, in Parkinson's, misfolded GCase proteins are implicated in causing the build-up of toxic forms of alpha-synuclein, a hallmark of Parkinson’s disease. Gain aims to modify disease progression by refolding the GCase proteins at the start of the disease cascade to prevent neurodegeneration rather than just masking symptoms.

With over 50 rare diseases tied to misfolded proteins, the potential impact of Gain's technology is far-reaching. The company's novel science provides hope for patients running out of options.

Financial performance and funding

As a clinical-stage biotech focused on research and development, Gain Therapeutics still needs to generate revenue. As a development-stage biotech, expanding Gain's pipeline requires significant funding. The company has previously bolstered its balance sheet through various public offerings.

R&D expenses accounted for most of the costs at $8.4 million, while general and administrative costs were $4.6 million. These expenses relate to advancing Gain's pipeline and operating as a public company. Gain has funded operations primarily through public offerings of common stock. In 2021, the company raised $46 million in gross proceeds, providing a runway into Q3 2024 based on current and projected burn rates.

As pipeline programs progress through more advanced clinical trials, R&D costs are expected to rise significantly. Gain will likely need to raise additional capital within the next 1-2 years to support late-stage development.

While additional funding will be needed to progress later-stage programs, Gain's current position provides resources to hit critical milestones. Continued pipeline development could also enhance partnership opportunities with larger pharmas.

Risks and challenges

While Gain's novel approach offers promise, the company still faces considerable challenges in translating its science into approved therapies that benefit patients.

The most significant risk is that Gain's treatments may not demonstrate sufficient safety or efficacy in clinical trials. Without proof that they deliver meaningful improvements for patients, approval will not be possible.

There is also no guarantee that regulators like the FDA will approve even if trials meet goals. The review process is complex, and the bar for approval is high regarding complicated gene therapies. The FDA could request more extensive clinical data, delaying availability for patients.

Additionally, drug pricing and insurance coverage pose hurdles. Given the investment required, Gain's therapies will likely carry high price tags. Ensuring fair patient access through a reasonable range is critical.

Competition from more prominent pharmaceutical companies is another risk if others pursue similar approaches to modifying protein misfolding. Gain will need to show clear clinical benefits over other emerging therapies.

Manufacturing complex gene therapies on a large scale also poses production challenges. However, Gain works with expert partners to optimize technical processes and mitigate manufacturing risks.

While meaningful obstacles exist, the immense need for transformative therapies keeps Gain motivated to refine its science and realize the full potential of correcting misfolded proteins. Delivering on that promise is imperative for patients running out of options.


With a promising novel approach backed by seasoned leadership, Gain Therapeutics represents an intriguing emerging biotech targeting high-value rare disease markets. Though early-stage and still requiring validation, the company's potential to address root causes aligned with growing interest in precision gene therapies. Gain offers an upside for investors with a risk appetite if its treatments realize the transformative potential of correcting misfolded proteins.

The views and opinions expressed herein are the views and opinions of the author and do not necessarily reflect those of Nasdaq, Inc.

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Ari Zoldan

Ari Zoldan is the CEO of New York-based Quantum Media Group, LLC. The company provides investor relations, public relations and equity research services to publicly traded companies. As an on-air media personality, Ari can be seen regularly on major media outlets and is frequently quoted in mainstream news outlets covering business, innovation and emerging trends.

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