Thalia Therapeutics Plc ($THAT)

So welcome back to another episode of the BioHub. Today, we're delighted to welcome on David Solomon, who's the CEO of Thalia Therapeutics, who are focused on advancing innovative RNA therapeutics and next-generation delivery technologies. Over the course of David's career, he's led multiple publicly listed and private biotech companies in both the U.S. and Europe, including Zealand Pharma and Silence Therapeutics. At Thalia Therapeutics, David is leading the company's strategic expansion into high-value RNA therapeutics with a focus on cardiovascular diseases and oncology, whilst advancing the company's proprietary Nuvec delivery platform. So David, it's an absolute pleasure to have you on. How are you?

Very well, and thanks for having me.

Yes. It's an absolute pleasure to have you on. So look, let's just start off with a little bit about your journey through the field, how you got to where you are today. So you've spent decades in biotech and RNA therapeutics across companies such as Silence Therapeutics and Zealand Pharma. Just talk us through what first attracted you to the industry and what have been some of the biggest lessons you've learned in your journey so far?

Yes. Thank you. Well, my journey actually started in academics. I was earlier a professor of both pharmacology and neurology at Columbia University School of Medicine in New York City for near 10 years. So I really started from an approach of a certain discipline about discovery of new ideas of mechanisms of action of, I think, trying to aspire towards fine science. But I left Columbia and really moved ultimately to an investment fund that I helped found called CARAT Capital Healthcare Ventures in New York City. And in doing that, we started applying capital to good science so that we could advance innovative medicines as an early and seed stage investor and then syndicate it with other good investors and advance the company with dedicated management teams. And so it was really the idea of merging together corporate finance on one hand and innovative science on the other that became sort of the 2 key pillars of my career. And ultimately, I went on to my happiest place being CEO of companies. I love working with high-performing teams and innovative assets and ultimately bringing really important products to patients, their families and their caregivers. And this was really the opportunity and the challenge at Zealand. We had discovered one of the first GLP-1 receptor agonists and ultimately did licensing deals with Sanofi, with Boehringer, with Lilly, among others, to advance these medicines now leading the charge in the treatment of not only obesity, but also diabetes. And so that innovation was so important, but bringing also the academic discipline and also the corporate finance discipline.

Amazing. So just talk us through, you mentioned some of the companies that you've worked at previously as CEO. What made Thalia Therapeutics the right opportunity for you at this stage in your career?

Well, as you know, in biotech and health care, you have to really be a futurist. You have to think not about the medicines that are going to be needed tomorrow, by patients, their caregivers, but medicines that will be necessary to treat serious disease in the next 20 years. So much as we have that approach at Zealand with the GLP-1 receptor agonist class as early as 2008, 2009, the same is true in RNA therapeutics. There are -- the success of COVID vaccines, mRNA was evident in how fast you could go to bring safe and well-tolerated solutions in very urgent conditions. But then companies like Alnylam have really led the charge on gene silencing, siRNA, double-stranded RNA that silences genes. And there are now approximately [ 6-ish ] products, RNA therapeutic products approved, generating significant $1 billion revenue today, but there's still lots to explore because those products target essentially genes only in the liver in hepatocytes, -- and there are siRNA medicines, but there are no, for example, microRNA medicines, although they're coming online to modify gene expression. So I thought there was still a lot of room for targeting different cells and organs for coming up with solutions of combinations for thinking about microRNA as a possible methodology. So the timing seemed ripe. And I like working in public companies insofar as you have access to capital. So if Thalia in its newest way of thinking can bring on innovative new therapeutic products that are RNA therapeutics, I think it's likely we can find interested investors, first retail investors on the London Stock Exchange but then institutional investors. And ultimately, as we advance those products really grow value for shareholders, but also advance products for patients, their families and caregivers.

Amazing. And yes, one of the things that was announced fairly recently was the name transition from N4 Pharma to Thalia Therapeutics. Just talk us through like why was that change important? And what does the new identity represent for the company now?

Sure. So Thalia in modern Greek means to blossom or to grow. And I really firmly believe that growing innovative ideas and assets and products is really the hallmark of the beginning of the journey of really good health care companies, good biotech companies. N4 Pharma had a very good product and approach in Nuvec, a delivery system for therapeutics. But in my view, this will be better served by bringing on our own proprietary therapeutics and then ultimately using those as both stand-alone and also with Nuvec in targeting different cells and organs for delivery of these therapeutics. And I thought that the combination together with discussions with our Board would bring a more potent offering for shareholder value, but also for patients and their caregivers.

Amazing. And just talk us through like what -- how would you describe the new direction of Thalia today? And just talk us through where do you see the company fitting into the broader RNA therapeutics landscape as well? Just talk us through that.

Sure. Well, when you think about other companies in the space, for example, companies that are doing siRNA gene silencing, leaders being Alnylam, of course, and Arrowhead, -- my former Silence, they're all targeting single target assets. They're all targeting essentially the liver because you can add GalNAc, which is a modified carbohydrate that binds to a specific receptor only in hepatocytes liver cells that target those cells. And then when you introduce that medicine inside the liver cell, they act catalytically to essentially reduce gene expression of the target gene and therefore, hopefully modify or cure disease. And that's been the hallmark of companies. And I thought the opportunity here for Thalia is to be able to think about maybe dual acting or bispecific siRNAs targeting multiple targets, not only in the liver, but also using Nuvec to be able to maybe load more or load different ratios of these bispecific medicines and also think innovatively for the future about how we target other cells and tissues, an area that is very interesting to the markets and to other companies in the space. So I thought we could essentially leapfrog hopefully beyond the innovation that other people have built to a next-generation RNA therapeutics company and really a European champion in the space. And so that was the aspiration. It's the goal. And together with my Board, it's really the strategic moment where we find ourselves today going forward.

Okay. Amazing. And so just talk us through your lead program targets both [ PCSK9 ] and [ Lp(a) ], which is particularly interesting because a lot of companies are targeting those pathways separately. Just talk us through like what makes your approach different compared to some of the other key players that are out there in the field.

Yes. No, I think that's an important differentiation. So there are already siRNA gene silencing medicines in exploratory clinical trial mode against Lp(a) and against PCSK9. In fact, there's one for PCSK9 that is already commercial inclisiran with Alnylam. But the point of Lp(a) is Lp(a) is a target inside the body that is determined at birth. And it turns out that if you have high Lp(a) levels, you can diet and exercise, you can become a marathon runner and Lp(a) levels will not go down. And if your Lp(a) is extremely high, your risk of an occlusive cardiovascular event like a heart attack or a stroke can be multiple folds higher than the general population. And it's already been well established through a range of different experimental methodologies that lowering Lp(a) reduces risk. So one company that's leading the effort here, Novartis, a large pharmaceutical company, as we know globally, is carrying out a Phase III study called HORIZON, where they're using a gene silencing medicine against Lp(a) and they're actually counting events, and they're trying to see does lowering Lp(a) by, say, 95% over the course of 3 months lower the number of events. If that turns out to be true, that will be sort of a halcyon moment, if you will, for Lp(a) being an important target, just like lowering LDL cholesterol through statins is an important methodology that has achieved obviously global, global success. So Lp(a) is a good target. Now PCSK9 is a target that tends to rise owing behavior. So if you're obese or need a highly processed food diet or have other comorbidities like type 2 diabetes, your PCSK9 levels can be high. And if you lower PCSK9, your LDL cholesterol goes down. Other people are doing the same approach with both siRNA, but even other approaches, we just saw the terrific results of Verve Therapeutics now owned by Lilly. -- published this week, this past week in the New England Journal of Medicine that showed that gene editing lowering PCSK9 can lower LDL cholesterol, and I would argue that will lower ultimately the risk. So we want to target both Lp(a) and PCSK9, but our differentiation is making a medicine that essentially can be introduced to patients once every 6 months or once a year because then you can target both genetic risk and also behavioral risk with almost assured compliance over a long period of time. And my belief is that will lower cardiovascular risk of events in global populations and I think be a very important and innovative offering for the marketplace, for physicians, for patients and their families.

Yes, exciting. And as you look ahead over the next year, 24 months, what are some of the next key milestones or developments that you and the team are most excited about maybe on a on a clinical or regulatory funding, business development? Is there anything that you can share on what you guys are excited about coming up?

Well, as already disclosed, either in other -- in press releases or other publications or podcasts, what we're focusing on in this period is actually using our dual acting or our bispecific gene silencing medicine against Lp(a) and PCSK9 in both murine or mouse experiments and also nonhuman primate or monkey experiments to establish, in fact, that the product will be safe and well tolerated and will have a modicum of efficacy. So those are experiments that are planned to be initiated this year in 2026. And as you may know, in the field, once you establish both safety and tolerability in nonhuman primates and cynomolgus monkeys and you show that you can lower the target, the FDA often will give companies or sponsors the allowance to go into pivotal type studies in humans. And so we believe by accelerating these activities in animal experiments in 2026, we'll be on a fast track to carrying out first human experiments and therefore, really be able to see the benefits of this approach. Not different than Verve did with their gene editing approach against PCSK9 and already Alnylam have done in their gene silencing siRNA medicines. And so really, this year is focused on essentially product development, regulatory discussions, animal experiments for both safety, tolerability and also efficacy and getting ready for human clinical trials.

Exciting. So just the dynamic of the company. So Thalia operates across different locations across, I guess, across the world. How would you build a strong culture and keep teams aligned when people are working across different countries and different time zones. Just talk us through that and as well as the culture that you're trying to build at Thalia as well.

Sure. But so Thalia is listed on London Stock Exchange on the AIM segment and is based in the United Kingdom. However, team members are obviously working across different geographies. And so ultimately, we see the company in a very lean and mean focused manner now to use the virtual methodology in the first stage of development and then increase our footprint, if you will, later as we advance and then can reasonably do that across different geographies. But right now, we're extremely focused on getting ready for the clinic. As CEO, one of the sort of, I think, hallmarks of that I hope works in my leadership role is essentially to bring on high-performing teams and colleagues that have experience in the field, working with a Board that is extremely experienced in both governance, corporate finance and the applicable science that we're working on. But ultimately, I can't score many baskets. It's really the team that does that. So I'm much more like a basketball coach in the leadership mode to essentially make sure they have good uniforms and lots of money and good practice facilities and the right culture to be able to advance the company and score those baskets, if you'll mind the analogy. And so we have some very, very fine members on our team that have terrific level of experience in RNA therapeutics and in manufacturing these products. And going forward, I think the team, together with myself and the Board will be able to meet all of the milestones that we hope to achieve in '26 and beyond and really grow the company for shareholder value. The asset earlier asset, Nuvec is extremely valuable insofar as we can use it as a delivery system. So the underpinnings of the company, N4 Pharma before we changed the name to Thalia, before we changed the strategy is still important and the shareholders that supported the company in the past, I'm grateful that they're still here with us, and we'll be able to hopefully enjoy the journey going forward. But essentially, now, it's about building an RNA therapeutics champion in Europe and globally and advancing important medicines first in cardiovascular care, but also in other fields as well.

Yes. Amazing. You mentioned some of the key players in RNA therapeutics previously, which is becoming an increasingly competitive space. Just talk through like what do you genuinely believe differentiates Thalia from other companies in the field. You obviously know the RNA space pretty well. What would you generally think that differentiates the company from others?

Well, I think that we understand not only the marketplace of RNA therapeutics going forward, but we understand all the technology so that rather than making similar approaches, we're actually advancing bispecific or dual-acting medicines, our first example being the dual-acting medicine against Lp(a) and PCSK9. And I think we're using Nuvec and perhaps other methodologies, we also are thinking about targeting other cells and tissues other than liver cells. And so I think all these things will allow us to sort of leapfrog over where people have been in the past 5 years. to a new vision and a new reality for RNA therapeutics companies that we hope are valuable and ultimately provide new and important products for patients, their families and caregivers. And obviously, there are lots of very fine companies out there, companies like Alnylam and Arrowhead and Silence. So our job is to be part of that ecosystem and really advance this type of medicine in all of the diseases where there's a lot of unmet need, and we think these medicines will play an extremely important role.

Yes. And you've been involved in RNA therapeutics long before the current wave of excitement around the sector. So you've sort of seen it in the earlier days, I guess. Where do you think the industry is still underestimated today in RNA?

Well, I think ultimately, these medicines will be mainstays in terms of both silencing genes that cause disease and modifying gene expression that cause disease. And therefore, as a class of medicine, I think both siRNA and microRNA and also mRNA will be very, very important and a growing modality. So it's really learning the lessons of where everyone has been. The real opportunity is that there are so many more organs and tissues to target other than just hepatocytes in the liver. So it's really the beginning of the journey, if you will, for this type of therapeutic. And as soon as we and others crack the nut of addressing other cells and tissues and new delivery systems in addition to the therapeutics, I think that there's an enormous number of diseases where there's unmet need where our medicines and the medicines of other companies in the space will be able to provide solutions.

Amazing. And this is a question that we would always finish with as well on the podcast. But if you were to sit down and have dinner with any 3 people from past or present, who would you go from why? It can literally be anyone. It does need to be someone from the industry, although it could be if you like. But yes, 3 people you'd like to sit down and have dinner with.

That's a tough question. You're really putting me on the spot, Tom. But thinking about that, I would say inspiration comes often orthogonally from outside of the field we're in. And it's also about people's strength and discipline and perseverance across different fields or disciplines that we can really learn from and then apply to health care and specifically biotech and specifically innovative medicines. And so thinking about that, I would say there are 3 people that I would love to talk to and learn from. First would be perhaps someone who's not -- anything to do with health care, but Sir Ernest Shackleton was an Antarctic explorer. And the boat that he was captain of called the Endurance, that was, I think, going to the South pole, the earlier part of the 20th century, that boat got stuck in ice flows and ultimately couldn't move. And he had to with his crew, essentially leave the boat and walk something like 800 miles, dragging a life boat and then navigating over icy waters to some polar ice station to get help and go back and rescue the rest of the team, and he did that and nobody died. And they all made it back to England in one piece. It was really a remarkable story. And so I would love to understand how he developed such perseverance and ability against all odds when obviously falling over dying was an obvious thing that could have happened to him and his crew. So the perseverance of Shackleton and his crew would be something I'd really like to learn from. In the realm of science, Marie Curie, one of the pioneering women scientists of her day in France, but with global impact. She won the Nobel Prize twice. And I'd love to learn how as a woman, she worked against the grain in 2 different fields, medicine and physics to make sort of key discoveries that were awarded with Science's highest prize. And what was her level of discipline and belief and thoughts about innovation. I'm sure that there's lots to be learned from her approach that was unique in the day and still today, almost unparalleled. And finally, in our space, Henry Tremere was the founding CEO of a very fine company called Genzyme since bought by Sanofi for something like $30 billion some years ago. But Henry Tremere believed in rare disease. And I think he did something like 30 deals to add small assets and small companies to Genzyme over time to build a powerhouse in lysosomal storage diseases, rare diseases where children are born normal. And then at 6 months, they look like they have a deficit and at age 1, they never walk and at age 2 or 3, they're dead. And he was able to figure out how to use gene therapy or replacement therapy of enzymes to treat these children and make them live normal healthy lives and make a very valuable company and really was a revolutionary in rare diseases, which is the mainstay of our approach to get medicines approved today. Sadly, Henry Tremere is no longer with us, but I'd love to sit down with him and learn about how he built a company based on so many transactions that ultimately generated not only huge shareholder value, but some of the best medicines to treat very difficult diseases in vulnerable people, small children. So I would say those would be the 3 people I'd love to dim with.

Yes. Amazing. Well, look, David, thanks so much for coming on and helping us out with this. It sounds super exciting, the new direction of Thalia Therapeutics now. So I'm excited to see the next milestones and inflection points that I'm sure we'll see over the next few months and year or so. So look, it was a pleasure to have you on. Thanks again, and...

Thanks so much for having me. I really enjoyed the conversation.