Q&A: Gain Therapeutics CEO Discusses AI-Driven Drug Discovery, Strategic Growth Plans

Gene Mack

Gene Mack became CEO of Gain Therapeutics in January 2025 after previously serving as interim CEO and chief financial officer for the company. Mack brings 25-plus years of experience to the leadership role for the clinical stage biotechnology company, having previously worked in areas such as clinical research, financing, investing, corporate strategy, and business development.

In an interview with Pharmaceutical Executive, Mack discussed his transition as the company’s new CEO, its use of physics-based artificial intelligence (AI) for drug discovery, the progress and financing of its lead drug candidate GT02287 for the treatment of Parkinson’s disease, and strategic decisions regarding clinical development, partnerships, and future growth.

PE: You’re fairly new as the CEO of Gain Therapeutics. Can you speak more about different aspects of the company, such as its physics-based AI, how it could be applied to this new AI paradigm, and speak more about your lead candidate?

Mack: I joined the company about a year ago as its chief financial officer. I had a connection to the board. The scientific founder is a CEO I covered as a cell side analyst, and we developed a relationship that continued for the next decade. Last year, he gave me a call since his CFO went off to do something in Europe, and he felt that the current management didn’t have a lot of experience with capital markets. So, they asked me if I would take a look. I have a neuro background, and since it was for Parkinson’s disease, it was natural for me to take the role of CFO.

The CEO and the board parted ways over business development and types of transactions that the company should be pursuing. In June, they agreed to disagree and I became the interim CEO, which was made permanent in January. Small biotech companies live through chronic periods of existential threats, with brief periods of enormous success if they’re good. But for the most part, there are a lot of existential threats out there. In a small company, a CEO has to be available at all times. So, that’s a challenge, but it’s very rewarding and I’m happy to be there.

We have enough capital to complete an interim analysis from our Phase IB trial (of GT02287), which we think will be a sufficient enough signal finding exercise to design Phase II. At that point, we’re going to share the interim results with our potential partners as well as the market. From there, we either raise additional capital on our own, with partners, or some combination of the two that allows us to maintain significant ownership of the compound.

PE: Are you putting forward additional candidates or are you waiting to see the results of the readout?

Mack: We have a backup portfolio of compounds that also target glucocerebrosidase (GCase), which is the target of GT02287. The interesting aspect is that it’s structurally distinct. In a nutshell, the Magellan platform was initially good at taking known compounds and figuring out the binding kinetics and could do some things intuitively. What we do now is bind kinetics for fragmented molecules that don’t necessarily exist yet but could potentially be formulated based on the structure that the platform builds. Then you see structures flickering in and out of view, you start to see things stick and not come off, because there’s a threshold. As that structure is built, that is a theoretical threshold.

I think the next thing that we need to improve upon is having it spit back more accurately and be something that can stabilize quickly. It takes a tremendous amount of data. Right now, AI is a shiny object, but there’s a million people working in the background to make sure that objects stay shiny. This includes constant data integration. If you don’t do it correctly, it won’t work properly.

PE: What can you tell us about the timeline for clinical data milestones?

Mack: In December, we received approval in Australia to start our Phase I study in patients with Parkinson’s disease. In the third quarter of last year, we reported safety and tolerability results from a health volunteer study. The first step in a Parkinson’s disease study is to conduct a health volunteer study for 14 days in order to make sure the drug is well tolerated. We saw the safety and tolerability profile that we wanted as well as target engagement. In health volunteers, we were able to increase Gcase activity, which was an important finding. That’s the target of GT02287. You shouldn’t see that in healthy volunteers. People in homeostasis work on feedback loops. When something shifts into an imbalance, the body works well at reacting quickly to compensatory mechanisms in order to nail it back down. Based on the snapshot that we took, we were able to see that the enzymes received 53% activation. To me, that’s the reason to believe that we’re on target going forward.

Now we have to demonstrate in another pilot study that it’s safe and tolerable. In our first study, we saw some grade 2 nausea, and we want to make sure that doesn’t turn into something worse, but there’s no reason to believe that it will. Nonetheless, we still need to do the three-month dosing study. We expect to see Gcase activity there as well, but we’re not sure if we’ll see a functional response after three months. Some of these patients have had toxic substrate building up in their brains for four years. Something working into that mechanism is going to take much longer to show functional employment, because you’re basically trying to stop the damage. You’re not repairing or masking anything. But if we can stop it in severe patients, we continue to move that treatment paradigm earlier as long as the therapeutic index remains appropriate.

PE: What are the next steps in the Phase IB study?

Mack: We’re going to enroll 15 to 20 patients, and we’re expected to start any day now. The open-label study will dose these patients for three months. We’ll watch enrollment from now through March. By the end of March, I expect to be able to tell the market what will be included in an internal analysis from the Phase I study.

There are a number of decisions that need to be made on the back of the Phase IB interim analysis. We’ll start incorporating and thinking about a Phase II design, but we might keep that protocol open and extend the dosing to 12 months. By the time the Phase IB data reads out, we will be able to incorporate that into the protocol amendment and extend the dosing. As a result, we’ll be able to get an answer much sooner than if we stopped the trial towards the end of this year. The Phase II readout won’t occur until some point in 2027. If I can start dosing patients for 12 months, beginning in the third quarter of this year, I’ll have that data a full year earlier. That’s important for the field, investors, and for patent life.

The next two big milestones coming are an enrollment update at the end of March with guidance on what the interim analysis would say.

PE: Tell us more about the financing of the company up to this point

Mack: It’s been very difficult. The private financing went smoothly but the public financing, that became a bit problematic. When the company went public towards the tail end of 2021, the market was starting to cool off. I would guess that Gain Therapeutics was one of the last companies to go public that year before the financing window went away completely. At the time, the company had about two years’ worth of cash. We went back to the market in 2023 and conducted a very difficult financing at around $2.75. We then did another financing round in June at $1.75.

All the while, the fundamentals of GT02287 have improved. It’s been elaborated through the data. So, the financing tracker has been inversed to the success of the company, and there’s a couple of reasons for that. I think early on, expectations were that this company would get acquired by a strategic partner quickly. With preclinical data, I think that was a bit naïve. The expectation crept out into the market, but there weren’t enough discussions about the clinical development decisions that needed to be made.

People felt that there was no conviction. Meanwhile, the strategic partners are at the gate. We could make a deal tomorrow. Most companies act favorably, but they didn’t consider whether the data will look as good three years from now as it does today. We don’t want to be unfair, but we also don’t want to leave a tremendous amount of money on the table. The early work we’ve done will significantly reduce that risk.

We’ve had some pressure to partner before our Phase IB trial, and we’ve been resistant to that because for little capital, we can deliver a Phase IB result, and then see if we’re still the right company to move forward with, and I think we are.

There’s a lot of debate on the board on what the company’s growth is going to look like in the next year. Is it going to be a partnership, a solo venture, or is it going to have another name on it? That’s something that will be determined by the data. But having activated Gcase in health volunteers, I am content to wait and see how this plays out.

PE: Would you envision that all eyes are on getting GT02287 to move forward?

Mack: Yes, the eyes were initially on Magellan and tweaking it in a way that it can be monetized. When I joined the company, I thought that was all wrong. We have a drug in clinical that will validate the platform rather than keep pumping out molecules that may or may not work. If they fail, it reflects poorly on Magellan. Let’s prove that those end products can make it into the clinic. Since coming in as CEO, I’ve converted us over a little more towards clinical operations and a little bit less towards bench research. It’s not less of an emphasis on bench research but right now, the growth area is in clinical operations.

The people running Magellan, and our early-stage pre-clinical research are awe-inspiring, because we have a pipeline that’s difficult to validate at low levels because of the productivity. We’re trying to consolidate some of that work and build the clinical operations team so that we can make good strategic decisions, which is where the company should have been headed as soon as GT02287 entered clinical development.