Zelluna utvecklar allogena ”off-the-shelf”-cellterapier för solida tumörer, där man använder celler från friska donatorer i stället för patientens egna. Huvudkandidaten ZI-MA4-1 kombinerar T-cellsreceptorer, som skräddarsytts för att känna igen cancermarkören MAGE-A4, med naturliga mördarceller som i sin tur avdödar tumörcellerna. ZI-MA4-1 är den första TCR-NK-terapin riktad mot MAGE-A4 som når klinisk prövning och utvärderas för närvarande i fas I-studien ZIMA-101 i Storbritannien.
Hela TCR-NK-plattformen skyddas av ett beviljat patent som ger ett starkt immaterialrättsligt skydd inom fältet – något som vd Namir Hassan har beskrivit som en stor strategisk fördel i takt med att plattformen utvecklas.
Utöver huvudprogrammet breddar Zelluna även sin pipeline. Genom ett utökat samarbete med Etcembly, AI-partnern bakom den ursprungliga MAGE-A4-receptorn, har man nu applicerat samma AI-drivna utvecklingsmetod på ett nytt målprotein, KKLC1.
Från regulatoriskt godkännande till första dos
Februari bjöd på två viktiga milstolpar: ett avtal med Medpace om att driva ZIMA-101-studien, samt godkännanden från den brittiska läkemedelsmyndigheten MHRA och en forskningsetisk kommitté avseende ansökan om klinisk prövning (CTA) för ZI-MA4-1. Tempot accelererade därefter under det andra kvartalet.
I maj aktiverades The Christie NHS Foundation Trust i Manchester, Europas största fristående cancercenter, som den första kliniska prövningskliniken för ZIMA-101. The Royal Marsden följde som den andra kliniken i slutet av juni. Dessa steg banade i sin tur väg för beskedet den 13 juli om att den första patienten hade doserats med ZI-MA4-1 på The Christie, vilket markerade den allra första kliniska utvärderingen av Zellunas TCR-NK-plattform.
Första säkerhetsdata ger grönt ljus
De första kliniska resultaten från ZIMA-101 presenterades kort därefter och visade en gynnsam säkerhetsprofil för den inledande patienten. Samtidigt rekommenderade den oberoende säkerhetskommittén (IDMC) att gå vidare med behandlingen av de kommande två patienterna i kohorten. Screening pågår brett för samtliga fyra tumörindikationer som ingår i studien: lungcancer, äggstockscancer, synovialt sarkom samt huvud- och halscancer.
Med data från den första patienten på plats och en pågående screening har Zelluna även säkrat det kapital som krävs för att driva programmet framåt.
Finansiering för att stötta den kliniska fasen
Parallellt med de kliniska framstegen har Zelluna stärkt sin balansräkning. En riktad nyemission och en spridningsemission som slutfördes i juni inbringade en bruttolikvid på cirka 58,2 MNOK. Kapitalanskaffningen stöddes av förhandsåtaganden på omkring 35 MNOK från befintliga aktieägare, däribland Gjelsten Holding, Sundt och Radforsk Investeringsstiftelse. Några dagar senare tilldelade Norges forskningsråd ytterligare ett anslag på 16 MNOK inom ramen för sitt innovationsprojekt för näringslivet, ett belopp som är helt öronmärkt för det pågående fas I-programmet.
Nyligen nominerade bolaget dessutom Martin Welschof, vd för BioInvent International, för inval i styrelsen, efter att den mångåriga ledamoten och medgrundaren Hans Ivar Robinson valt att avgå.
Q&A med vd
Nu när det kliniska arbetet är i gång fortsätter cellterapiområdet att attrahera ett stort strategiskt intresse. Ett aktuellt exempel är AstraZenecas förvärv av EsoBiotech för cirka 1 miljard USD, vilket baserades på data från en enda patient. BioStock bad vd Namir Hassan att reflektera över kvartalets framsteg och vägen framåt.
Namir, you have led the development of the TCR-NK platform since joining the company in 2018. When the first patient was finally dosed in July, how did that feel?
– It was a very special moment, both professionally and personally. I joined Zelluna in 2018, when TCR-NK was still essentially an idea and a scientific hypothesis. To have been part of the journey of taking that idea, building a platform around it, developing ZI-MA4-1 and ultimately seeing it reach the first patient was incredibly special.
– What made it particularly meaningful was knowing how much work from so many people had gone into reaching that moment. Taking an entirely new cell therapy concept from an idea into the clinic is incredibly difficult. It has required years of scientific innovation, preclinical development, manufacturing, regulatory and clinical work, and a tremendous amount of resilience and problem-solving across the team. Many people at Zelluna have devoted a significant part of their professional lives to getting us to this point, and I think everyone involved should feel enormously proud of what we have achieved together.
– At the same time, when you reach the clinic, the significance of what you are doing becomes very real. There is a patient at the centre of everything, placing their trust in the therapy, the clinical team and ultimately in us. That brings both excitement and a great sense of responsibility.
– We have since reported favourable initial safety observations from that first patient, with no dose-limiting toxicities observed, and the Independent Data Monitoring Committee has recommended that we continue enrolment at the first dose level. That is an encouraging first step, but we remain at a very early stage. Our focus now is on carefully executing the study and generating the clinical data that will allow us to understand the potential of ZI-MA4-1 and our broader TCR-NK platform.
Q2 marked Zelluna’s transition into a clinical-stage company. What do you see as the most important achievements during the quarter and immediately following the period?
– There have been several important achievements, but perhaps what I am most pleased about is that we have continued to deliver against the milestones we set ourselves. At the beginning of the year, we said we would move ZI-MA4-1 into the clinic, activate our clinical sites and begin generating clinical data from mid 2026. We have now delivered on each of those objectives.
– That is important because developing a novel cell therapy is complex, and it is not always easy to do what you say you are going to do, when you say you are going to do it. There are many interdependent pieces – manufacturing, regulatory, clinical sites and patient recruitment – that all have to come together. I think the team’s ability to execute consistently across all of these areas is something we should be very proud of.
– During the quarter, we activated The Royal Marsden as our second clinical site alongside The Christie, giving us two leading UK cancer centres recruiting into ZIMA-101. Immediately following the quarter, we dosed our first patient with ZI-MA4-1, marking both the first patient treated with a Zelluna-developed cell therapy and the first clinical evaluation of our TCR-NK platform.
– Importantly, we have already taken the next step. We recently reported favourable initial safety observations from that first patient as mentioned earlier. These are the first clinical data generated from our TCR-NK platform and, while still very early, they are an encouraging start.
– Safety is also becoming an increasingly important differentiator in cell therapy. We know the significant toxicities that can be associated with conventional autologous T-cell therapies, and we are also beginning to see safety considerations emerge with some of the newer in vivo CAR-T approaches. This reinforces why we believe the potential safety characteristics of an NK-cell-based approach could be important. It is far too early to draw conclusions from a single patient, but the initial observations are encouraging and we now need to see how that profile develops as we treat more patients.
– We also strengthened our financial position through the NOK 58.2 million financing and the NOK 16 million grant from the Research Council of Norway, providing additional support as we continue clinical execution and generate further data.
– So, when I look back at Q2 and the period immediately afterwards, I see a company that has moved from preparing for the clinic to treating patients and generating its first human data, while continuing to deliver against the plan we set out. That is a significant transition for Zelluna and gives us a strong foundation for the next phase of the programme.
You dosed the first patient with ZI-MA4-1 in July. Why is this milestone important not only for the lead programme, but also for Zelluna’s broader TCR-NK platform?
– The importance goes well beyond ZI-MA4-1. This is the first time our TCR-NK platform is being tested in humans, so every patient gives us an opportunity to learn not only about the product, but also about the underlying platform.
– ZI-MA4-1 brings together the key elements of our approach: the ability of a TCR to recognise cancer targets with high precision, combined with the inherent anti-tumour properties and potential safety advantages of an allogeneic NK cell. What we are now beginning to test clinically is whether those attributes can translate into meaningful benefits for patients with solid tumours.
– The study is therefore designed to tell us much more than whether ZI-MA4-1 is safe and whether we see signs of clinical activity. We want to understand what happens to these cells in patients –whether they reach the tumour, how they interact with the tumour microenvironment, and whether we can demonstrate the biological activity that we have seen preclinically. Those insights can help us understand how the platform performs in humans and inform how we develop future TCR-NK products.
– That is what makes this stage so important strategically. ZI-MA4-1 is our lead product, but our ambition has always been broader than a single target or programme. If the clinical data support the underlying biology, we have the potential to apply the platform to additional cancer targets and build a broader pipeline of off-the-shelf TCR-NK therapies.
– So we are now beginning to answer two questions in parallel: what is the potential of ZI-MA4-1 as a therapy, and what can the clinical data tell us about the broader potential of the TCR-NK platform? That is why reaching the clinic is such an important value inflection point for Zelluna.
With recruitment now continuing at both The Christie and The Royal Marsden, what are the next key clinical milestones investors should be looking for?
– The immediate priority is to complete recruitment of the first dose level. Following the IDMC recommendation, we can now enrol the remaining two patients in this first cohort, and our focus is on doing that carefully and efficiently across our two clinical sites.
– From there, we will continue the planned stepwise dose-escalation process. At each stage, patient safety remains the priority, while the accumulating data will increasingly allow us to look beyond safety and begin to understand the biological and clinical activity of ZI-MA4-1.
– An important aspect of ZIMA-101 is that we administer three doses within a treatment cycle, with the potential for patients to receive a second cycle. As the study progresses, we will therefore be looking at the totality of the data – safety and tolerability, what happens to the cells in patients, evidence of biological activity, and ultimately whether we begin to see signs of anti-tumour activity and durability.
– For investors, I think the key point is that the data will build progressively rather than around a single binary readout. We have now generated the first encouraging safety observations. The next milestones are completing the first dose cohort, progressing through dose escalation and building a richer clinical dataset as more patients are treated and followed over time.
– We have always said that 2026 would be the year in which we begin generating human data from our TCR-NK platform. We have now started to deliver on that, and the focus for the remainder of the year is to continue executing the study and allowing that clinical picture to develop.
What are you hoping to learn from these first patients beyond safety, particularly about the biological activity of the TCR-NK platform and its potential in solid tumours?
– Beyond safety, one of the most important things we want to understand is whether the biology we have demonstrated preclinically translates into patients. That is really where the value of these early patients extends beyond simply establishing that ZI-MA4-1 can be administered safely.
– We want to understand what happens to the TCR-NK cells after administration – whether we can detect them in the circulation, and importantly whether we see evidence that they are reaching the tumour. We will also be looking for pharmacodynamic evidence that the cells are doing what they were designed to do once they encounter cancer cells.
– Solid tumours remain particularly challenging for cell therapies. It is not enough simply to have a cell that can recognise a cancer target; it needs to reach the tumour, remain functional within a difficult tumour microenvironment and generate sufficient anti-tumour activity. These are some of the fundamental biological questions we have designed the study to answer.
– Of course, ultimately we want to see clinical responses. But particularly in these first patients, understanding the relationship between dose, exposure, biological activity and any emerging signs of anti-tumour activity will be extremely valuable. We are also interested in durability and whether repeat treatment through a second cycle can potentially extend or deepen the effect.
– What is particularly important for Zelluna is that these learnings are not confined to ZI-MA4-1. They can tell us how our TCR-NK cells behave in humans and help inform how we optimise the platform and develop future programmes. So even at this early stage, we are beginning to generate information that could be important for both the lead programme and the broader potential of the platform.
Zelluna raised NOK 58.2 million during the quarter and was subsequently awarded a NOK 16 million Research Council grant. How does this strengthen the company’s ability to execute its clinical and strategic priorities?
– The financing was important because it strengthened our position at precisely the point when Zelluna was moving into the clinic. Together with the NOK 16 million Research Council grant, it provides additional financial flexibility as we execute ZIMA-101 and generate the clinical data that we believe will be central to the next phase of value creation for the company.
– We have been very disciplined in how we deploy capital. Our priority is clear: successfully execute the clinical programme and reach the key data points that will allow us to better understand the potential of ZI-MA4-1 and the broader TCR-NK platform. The additional funding gives us greater capacity to do that while maintaining flexibility around our future strategic choices.
– More broadly, we are entering a period where clinical data can materially change the strategic opportunities available to a company. We have seen that repeatedly across the cell therapy sector. Strengthening the balance sheet therefore gives us not only greater ability to execute the study, but also greater flexibility to respond to opportunities as the clinical picture develops.
– Our approach remains to be disciplined with capital, focused on the milestones that can create the greatest value, and sufficiently flexible to pursue the right strategic opportunities as they emerge.
There has been significant strategic investment and transaction activity across cell therapy, often driven by encouraging early clinical data. How do you see Zelluna positioned within that landscape as you begin generating human data?
– I think it is a very interesting time for cell therapy and particularly for next generation “off the shelf” cell therapies. We continue to see significant strategic investment and transactions across the sector, and, importantly, we have seen that encouraging clinical data can create substantial value relatively early in development. That reinforces the importance of the stage Zelluna has now reached.
– Where I believe Zelluna is particularly well positioned is in the differentiation of our approach. We combine the targeting precision of TCRs, which gives us access to intracellular cancer targets, with an allogeneic NK-cell platform designed for off-the-shelf use. We are also focused on solid tumours, where the need for effective cell therapies remains very significant and where there has historically been much less clinical success than in haematological cancers.
– Safety could also become an important part of that differentiation. We know that toxicity and complexity remain challenges for existing autologous T-cell therapies, and safety considerations are also emerging with some newer “off the shelf” approaches. It is far too early to draw conclusions about ZI-MA4-1 from one patient, but our favourable initial safety observations are encouraging and we will be watching this very carefully as the dataset grows.
– Ultimately, strategic interest follows compelling data. We have now entered the clinic and generated our first human safety observations. Our job is to execute well, build the clinical evidence and demonstrate what this platform can do in patients. If we can do that, I believe Zelluna will be very well positioned to participate in the significant strategic interest we continue to see across the cell therapy sector.
Beyond ZI-MA4-1, how are you thinking about the broader potential of Zelluna’s TCR-NK platform and pipeline?
– Our ambition has always been broader than ZI-MA4-1. We see ZI-MA4-1 as both a potential therapy in its own right and, importantly, as the first clinical test of the underlying TCR-NK platform.
– That is why the data we generate through ZIMA-101 are so important. We are beginning to learn how our TCR-NK cells behave in patients – their safety, trafficking and biological activity – and those insights can inform how we optimise the platform and design future programmes. In that sense, every piece of clinical learning from ZI-MA4-1 has the potential to extend beyond MAGE-A4.
– One of the attractions of the platform is its potential modularity. The NK-cell backbone can potentially be combined with different TCRs to address additional intracellular cancer targets, giving us the opportunity to build a broader pipeline while leveraging much of the manufacturing and development infrastructure we have already established.
– We are already taking steps in that direction, including our work on additional targets and our collaboration with Etcembly to apply AI-enabled TCR engineering to KKLC1.
– Ultimately, our vision is not to build a single-product company. It is to establish TCR-NK as a differentiated, scalable approach to treating solid tumours and, as the clinical evidence develops, use those learnings to build a pipeline around the areas where we believe the platform can have the greatest impact.
Zelluna has also recently announced a proposed change to the board. Can you briefly put that change into context and explain how you see the board supporting the company through this next stage of development?
– This is a proposed Board change, with Martin nominated for election at the upcoming Extraordinary General Meeting. We are delighted with his nomination. He brings extensive international biotech experience and a strong track record across company building, financing and strategic transactions, which we believe will be particularly valuable as Zelluna enters this important clinical and strategic phase. More broadly, we have a highly experienced Board, and its guidance and support will continue to be important as we generate clinical data and consider the opportunities that may emerge from the platform.
What would success look like for Zelluna by mid-2027, not just clinically but for the company as a whole?
– More broadly, success for Zelluna by mid-2027 would be to have transformed the company from one entering the clinic into one with a growing body of patient data that demonstrates the potential value of our TCR-NK platform. That should put us in a very different position – scientifically, clinically and strategically – and give us genuine options for how we maximise the value of what we have built.
– Clinically, we would want to see the encouraging initial safety profile continue as we treat more patients, alongside evidence that the cells are behaving as we expect biologically and, ultimately, signs of meaningful anti-tumour activity. Importantly, those data should tell us not only about ZI-MA4-1, but also give us increasing confidence in the broader potential of the TCR-NK platform.
– Alongside the clinical programme, success means continuing to strengthen the foundations around the platform – advancing our manufacturing towards greater scalability and improved economics, developing our pipeline thoughtfully, and remaining disciplined about where we invest our resources.
– And, of course, compelling clinical data can create significant strategic opportunities. By mid-2027, I would like Zelluna to be in a position where the strength of our data and the differentiation of our platform give us real strategic optionality that can maximise the value of the platform for our shareholders and, importantly, accelerate its development for patients.
– Ultimately, we started with an idea that TCRs and NK cells could be brought together to create a new way of treating solid cancers. We have now taken that idea into patients. Success in 2027 would be to demonstrate that this idea can translate into something truly meaningful for patients – and, if we can do that, I believe it could open a very exciting new chapter for Zelluna.
Innehållet i BioStocks nyheter och analyser är oberoende men BioStocks verksamhet är i viss mån finansierad av bolag i branschen. Detta inlägg avser ett bolag som BioStock erhållit finansiering från.
