BIOQUBE VENTURES  |  PORTFOLIO INTERVIEW

Built with conviction

A Conversation with Temmune Therapeutics

Built out of Bioqube’s venture creation model, Temmune Therapeutics is developing a potential first-in-class oral Kv1.3 inhibitor designed to quiet the harmful immune cells driving chronic inflammation, while preserving the immune protection patients need. Bioqube backed a contrarian hypothesis, funded it as a project, selected a new molecule and incorporated the company around it at the end of 2024. Leading Temmune is Joris De Maeyer, Bioqube’s Entrepreneur in Residence and now Temmune’s CEO.

Temmune did not come across our desk as a ready deal. How was the Kv1.3 opportunity identified, and why did Bioqube decide to build a company around it?

JDM: Kv1.3 was already a well-known target in autoimmunity and inflammation. Pharma had circled it for years but had consistently failed to drug it with small molecules. The program reached us through Metrion, a specialist ion channel CRO that was seeking funding for a molecule with interesting but limited data in autoimmune models, but safety findings at therapeutically relevant doses.

Our hypothesis was that part of that problem came not from the molecule but from how it had been formulated before being dosed. So at exactly the point where others were no longer willing to invest because the compound has a narrow therapeutic window, we decided the hypothesis was worth testing. It proved partly correct, and the work that followed led us to select a different molecule with a markedly improved therapeutic window.

The program was initially financed as a project within Bioqube’s venture creation model. At the end of 2024 the intellectual property was transferred into a NewCo, which we named Temmune Therapeutics, after the specific immune memory cells (Tem cells) we are targeting. We did not wait for a de-risked asset or a complete team. We built a structure around a scientific opportunity we believed others had overlooked.

What makes Kv1.3 a unique target, and why could blocking it be meaningful in autoimmune disease?

JDM: Think of certain immune cells as smoke alarms with a memory. They remember what they have encountered and react very quickly when they see it again. Normally that is protection, but sometimes those alarms become too sensitive and are triggered repeatedly, and that is when you get chronic inflammatory disease, in the skin, the gut, or the lung, depending on where the alarm sits. Kv1.3 is the power switch of that alarm. By blocking it, we quiet the cells that drive chronic inflammation while leaving the protective immune system intact.

Kv1.3 is a potassium channel that helps these cells stay activated. Its biology has long been validated by toxins from sea anemones and scorpions that block the channel at its opening, but nobody could turn that into a convenient medicine. What attracted us was the chance to do it with a small molecule, which opens up oral dosing and the potential to reach disease-relevant tissues.

Our lead molecule is mechanistically differentiated from these toxins. These approaches plug the pore, like a cork in a bottle. Ours works like a key in a lock: it holds the channel in an inactive form, making it much harder for those cells to sustain their inflammatory response. That is why we believe this can be a first-in-class inhibitor for the target.

You stepped in as Entrepreneur in Residence. What does a company gain from having an operator from the investor side in the driving seat?

JDM: Continuity. I encountered the program from the investment side and then stepped into it operationally, so the original investment hypothesis, the company creation and the company today are connected by the same thread. That is institutional memory, and it matters most at the turning points, when you are making a decision or a pivot on the back of new data. While it was still a project, we were already testing the core assumptions, guiding the molecule selection and shaping the development plan. When it moved into a NewCo, no time was lost transferring know-how to a new team. I continued to sharpen the differentiated story, stepped into the CEO role, and built the team around the asset.

It also fits how we operate. Temmune runs a virtual model with no labs of its own. We keep the internal organisation deliberately small and build the right external team around it, CROs, consultants, scientific and clinical advisors, so we can bring in exactly the right expertise at exactly the right moment. The structure around the company has changed since the beginning. The heart of it has not.

Bioqube built this company from day one. Where has it been most instrumental?

JDM: First, being willing to invest when most investors would not, and seeing the opportunity through a complicated data set rather than being scared off by it. The molecule had safety issues. We had a clear hypothesis that the intrinsic value was there and that it would take time and money to bring it to the surface.

Second, staying committed when the program did not follow a straight path. The initial hypothesis proved only partly correct, and we then decided to invest additional time and resources in finding a new molecule. Without that, the program would have stopped and today’s lead molecule would never have existed. Drug development is never a straight line from A to B. It is spaghetti, and navigating it takes trust, patience and an investor who is not too short-sighted on individual data points.

Third, everything beyond the financing: helping build the team and, critically, preserving the room to pivot. If the intrinsic value is there, you should never make the decision on a single data point. A creative team can often unlock value in an asset that initially looks unremarkable, while even a hot asset can struggle if the team cannot adapt.

Most attempts at building a biotech from scratch fail long before the science is tested. What makes venture creation so unforgiving, and what makes Bioqube’s model work?

JDM: Biotech is unusual in that the decisions that ultimately determine success or failure are often made at the moment you have the least money, the smallest team and the thinnest data package. Good science alone is nowhere near enough. From the very beginning you need a view on the end goal: the patient, the commercial story, the competition, the translational path, the intellectual property, how developable and how manufacturable it is. A wrong early decision costs enormous time and can cost you the entire investment thesis.

And no model, however smart, makes biology predictable. What a venture builder can make repeatable is the process around it: how opportunities are assessed, which critical experiments get prioritised, which questions are asked, which people are engaged, how the team is built, and how capital is allocated around value inflection points. Chance favours the prepared mind. You cannot control the biology, but you can make sure that when the data arrive, everything around them is optimal.

Where does the program stand today, and what are the value inflection points over the next 12 to 18 months?

JDM: Since incorporation and the transfer of the IP, we have built a much deeper understanding of how our molecule locks the channel in its inactive state, which has considerably strengthened our differentiation. We have also advanced the molecule towards the key regulatory safety studies, established a scalable manufacturing process capable of delivering kilogram quantities, and substantially strengthened our understanding of its pharmacokinetic profile.

The next 12 to 18 months are about completing the regulatory safety package, preparing the compound for clinical use and getting to first-in-human dosing.

Atopic dermatitis is a competitive, biologics-dominated market. Why is it the right entry point, and where does Temmune go from there?

JDM: It looks crowded, but it is crowded in the development landscape rather than on the market itself, and there is a good reason for that: there is a clear gap in the treatment paradigm. Patients start on topical creams, often corticosteroids, but in more severe disease they often need systemic therapy. Injectable biologics have transformed treatment, but not every patient responds adequately and many patients would prefer an oral option. Oral JAK inhibitors can be highly effective, but their safety warnings have pushed them later in the treatment pathway, particularly in the U.S., where they are generally reserved for patients not adequately controlled with other systemic therapies, including biologics.

That leaves a clear opportunity for an oral treatment that combines meaningful efficacy with a differentiated safety profile. An oral that is safe and effective could become a very attractive option for both physicians and patients. Atopic dermatitis also has a practical advantage: it is one of the few indications where you can run a clinical Phase 2 proof-of-concept study with regulatory-relevant endpoints over roughly three months, where other indications can require more than a year.

But it is not the only potential application of Kv1.3. We are also exploring indications such as psoriasis, severe asthma, inflammatory bowel disease, lichen planus, with emerging evidence pointing to potential applications in certain muscle and cardiovascular diseases as well. We are letting the biology guide where we expand next. If the molecule proves safe and effective, a Kv1.3 blocker becomes a pipeline in a drug: one asset, multiple indications.

Talk us through the path to value creation for Bioqube and its investors. How does pharma look at Temmune?

JDM: Bioqube was the founding investor and remains the largest shareholder, with a significant equity stake. Value has been created since day one by progressively navigating the remaining development risk. Clinical proof of concept is the most important inflection point, and the key upcoming step is completing the safety package and moving into the clinic.

We are already seeing interest from pharma. This is a well-known target, and the industry is actively scouting for safe, effective oral treatments in chronic inflammatory disease. What they need to see is a pharma-grade data package. Our job is to build that while maintaining optionality, so that when the moment comes we can choose the route that creates the greatest value for Bioqube and its fellow shareholders.

On a personal note, what drives you to build Temmune?

JDM: The combination of science, creativity, building something from the ground up, and ultimately, the opportunity to make a real difference for patients. That is what keeps everyone in this industry going, and here you get all four at once, on a target where a real medicine for patients is within reach.

And finally, as a true Belgian: what is your favourite beer, and where do we find you drinking one?

JDM: It is no secret, Duvel. And if I am allowed a second, Orval. You can find me enjoying one after a game of futsal with the team during the ‘third half’.

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