This audio is automatically generated. feedback.
Welcome to today’s Biotech Spotlight, a series highlighting companies creating breakthrough technologies and products. Today we feature Gain Therapeutics, a biotechnology company developing early-stage treatments for Parkinson’s disease. The company is adding new executives to its C-suite.
Dr. Jonas Hannestad, Chief Medical Officer, Gain Therapeutics
Used with permission from Gain Therapeutics
The funding landscape for early-stage biotech companies remains fraught with risk, even for companies with promising science in areas of unmet medical need. Maryland-based Gain Therapeutics, whose lead candidate is designed to address the root cause of Parkinson’s disease, had to navigate these difficult conditions while awaiting Phase 1 trial results by the end of the third quarter.
Perhaps new faces at the executive level will bring change to Gain. In the first half of this year, the company New interim CEO and Chief Medical Officerwhile setting prices $11 million public offering It is taking an unconventional approach to Parkinson’s disease by tackling the genetic mutations thought to lead to loss of motor function in Parkinson’s patients.
Earlier this year, the company Preclinical study results The study showed that cognitive function improved in mice compared with mice that were not given Gain’s treatment, GT-02287, which targets an enzyme coded for by a mutation in the GBA-1 gene. The company is also preparing to release results from a Phase 1 trial that showed safety and tolerability in healthy volunteers before moving on to mid-stage studies in Parkinson’s patients.
“The biology is very complex and a lot of work has been done on alpha-synuclein, the hallmark protein of Parkinson’s disease, but there have been failures. That’s where other approaches like GBA-1 come in.”
Dr. Jonas Hannestad
Chief Medical Officer, Gain Therapeutics
In an interview with PharmaVoice, Gain’s Chief Medical Officer, Dr. Jonas Hannestad, who joined the company in April, discussed how the biotech is embracing new disease-modifying approaches to intractable neurodegenerative diseases, an industry that is more scientifically collaborative than ever before, and how it is navigating a challenging biotech funding environment with a focus on breakthrough science.
PHARMAVOICE: Gain has experienced a lot of leadership turnover, and you’re a relatively recent hire. How have these personnel changes and financial hurdles affected your work on the clinical side of the company?
Dr. Jonas Hanestad: The departure of a former CEO is always disruptive. However, some of our directors who have experience running a company have become more involved in the day-to-day operations, which has been very helpful. They are supporting not only the interim CEO, but also me and my team in clinical development. This is a good sign.
Financially, it is always a challenge for small biotech companies, whether private or public, to have enough funding and resources to conduct optimal clinical development compared to larger companies. But this is a problem I know well because it is the same for many small companies. You have to spend more time making sure that the studies you design are optimal to get the key results you need while at the same time using as little money and time as possible.
Is it harder for small biotech companies to walk that line than it was before?
I think that’s certainly true. Where I was before Gain ran out of capital in late 2022, it was one of those waves where a lot of companies struggled. But there were biotech companies that had enough capital to continue operating after that. The financing environment in biotech hasn’t improved much, and companies continue to go under because they can’t raise additional capital. It’s been difficult, and as far as I can tell, it’s not getting much better.
Tell us about GT-02287 and how it became a potential treatment for Parkinson’s disease.
Among people with genetic risk factors for Parkinson’s disease, the most common is the GBA-1 mutation, which increases the risk of developing Parkinson’s disease by about three to five times. It is also a more severe form of the disease, with a faster progression and a higher prevalence of cognitive impairment. Gain has a computational platform to model the structure of proteins that may be useful targets and to understand how small molecules can bind to these proteins and have an effect on the disease. In the case of GT-02287, the idea was to find a molecule that could bind to the enzyme encoded by GBA-1. We have just finished a Phase 1 study, but it was safe and well tolerated in healthy volunteers, so we plan to move to patient studies in the near future.
How would you assess the overall current state of Parkinson’s research and why do you think it is an important area of research at this time?
Parkinson’s disease is the second most common neurodegenerative disease after Alzheimer’s disease, affecting approximately one million people in the United States alone. Many treatments have been approved for Parkinson’s disease, but they are all symptomatic and therefore effective in the early stages when patients are newly diagnosed and beginning to experience symptoms, and can be effective for several years. However, as the underlying disease progresses, these treatments begin to lose efficacy, causing worsening symptoms, greater disability, and ultimately loss of independence.
Most of the effort in the last 5 to 10 years has been directed at finding a treatment to alleviate the disease. Why can’t anyone figure it out? The biology is very complex, and a lot of effort has been focused on alpha-synuclein, the hallmark protein of Parkinson’s, but there have been failures, and that’s where other approaches, such as GBA-1, come in.
After years of symptomatic treatment, disease-modifying treatments for Alzheimer’s have reached a turning point. What is the turning point? Will similar successes be seen in Parkinson’s?
I’ve spent most of my career studying the three major neurodegenerative diseases: Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis, and they have a lot of commonality. What’s really changed is our understanding of the genetics has not only revealed the causes, but also revealed specific pathways that are abnormal in the cells. In Alzheimer’s, we see a lot of genetic hints that point to neuroinflammation, and companies have been targeting those pathways. In Parkinson’s, we see a lot of mutations in mitochondrial function, and GBA-1 points to not only the enzyme encoded by this gene, but different pathways that impact and maybe benefit Parkinson’s.
How does GT-02287 position itself relative to other Parkinson’s disease drugs currently in development?
There is currently a lot of effort focused on monoclonal antibodies targeting alpha-synuclein, with Roche’s ongoing program being a prime example, and Biogen and AbbVie each having one in development that they have since discontinued, so the jury is still out on alpha-synuclein.
Regarding GBA-1, there are two other companies in the field: Bial in Portugal, which is in Phase 2, and Vanqua in Chicago, which is currently in Phase 1. As far as we know, their molecule directly activates the enzyme, but that’s only a small part of it, because mutations cause misfolding in the cell, which leads to stress. What we’ve demonstrated with our molecule is that when you bind to the enzyme, it reduces the propensity for misfolding. So we think that’s what sets the Gain program apart.
The Michael J. Fox Foundation is funding your research – does that allow you to connect with knowledge-sharing networks between companies and researchers working in this field?
A big change over the last decade or so is that companies have become more willing to have pre-competitive discussions, sharing information about running clinical trials, identifying patients, etc., without sharing molecular details. I was at the Michael J. Fox Foundation conference in Washington DC about a month and a half ago, where representatives from pharmaceutical companies in the Parkinson’s space came together to discuss a new diagnostic framework. This is a great example of the parties finding common ground.
