My name is Roy Buchanan. I'm a biotech research analyst, and we're happy to have HOOKIPA Pharma here with us. We've got Reinhard Kandera, Chief Financial Officer on the pharma side there, and Mark Winderlich, Chief Development Officer. You can correct my pronunciation, please. Happy to have Mark and Reinhard here with us. Tell us about the HOOKIPA story. Really love the platform and some pretty important data and progress coming up. Maybe, Mark or Reinhard, give us an intro to HOOKIPA, just basically what the company's founded around, what the main programs are.
Yeah, so happy to do that. And thanks for having us here. So I would say the key takeaway message about our technology is its ability to generate high levels of antigen-specific CD8 T cells. And we do that by making use of the natural ability of RNA viruses to generate those huge T cell amounts. And by genetically engineering the RNA virus, we direct that natural immune response against specific targets, be it cancer cells or be it virally infected cells. And on the basis of that technology, we've developed a pipeline. Our lead product is in phase II development. We've shown good data in head and neck, first line, in combination with pembrolizumab. We've got a significant partnership with Gilead in HIV and hepatitis B, with 2 phase I trials going on. And even more importantly, our technology is broadly applicable. We can essentially encode any antigen.
We do have more possibilities in the early pipeline. Also, I have to say, at the moment, we are focusing on progressing our lead program into a pivotal trial to gain registration in a fast and efficient manner. We'll certainly talk more about that trial.
OK, yeah, great. I'd love to just have to say that one of the scientific founders, Rolf Zinkernagel, won the Nobel basically because the virus was so good at activating T cells, he could work out how T cells work, right? And that's really kind of yeah. And I think you guys have shown best-in-class T cell responses. I still haven't seen anything quite matching what you guys can do in people. So all right, anyway, Mark, so you recently joined. How long have you been with the company? Where were you before? Just give us your background and what brought you to HOOKIPA. And then what have you been tasked with at the company?
Yeah, thank you, Roy. And you pronounce my name very well, by the way. Yeah, I joined only one month ago, but I enjoy it a lot already. I'm, by education, a biostatistician and biologist with focus on biomedicine. I worked since approximately 15 years now in the biotech industry, in early phase, in mid-clinical development phase, late phase, as well as submission, approval, and launch. I have been mainly working in oncology, bringing a drug from the early days in the lab to submission and approval in the U.S. and in Europe. This drug was or is Monjuvi, a CD19 Fc-enhanced antibody in lymphoma in combination with lenalidomide. I later worked then for Constellation Pharmaceuticals. I was leading there the R&D and working mainly on a BET inhibitor, pelabresib, which went into phase III clinical development at this time in combination with Jakafi in myelofibrosis.
The trial just read out last year. This was the reason why MorphoSys was then acquired by Novartis. Just before joining HOOKIPA, I was working for Evotec and BMS, leading their big partnership developing and discovering molecular glues in oncology. It was a very rich pipeline of tiny programs. As I said, since a couple of weeks, I'm now with HOOKIPA. What attracted me to HOOKIPA? You said it. I think HOOKIPA has the best platform for cancer vaccination. Cancer vaccination, for me, is in a renaissance area or age, I would say. It was very interesting 15-20 years ago. But the technology was not there. We didn't know how immune modulators could be combined with cancer vaccinations. This completely changed. We have now great technologies. HOOKIPA is a very good example. We have the checkpoint inhibitors. We have the immune modulators.
Now we can unlock the full potential of cancer vaccinations. This was the main reason why I was attracted to HOOKIPA. Obviously, the clinical data look very compelling. From my perspective, I have been involved in a couple of phase three trials so far. From my perspective, definitely approvable. HB-200, our HBV16 targeting drug, has really a potential for best-in-class and also first-in-class.
OK, great. Thank you. So let's maybe start on HB-200, the lead candidate. Just give us a description of what it is, where it is at in the clinic, what you've seen so far. And the planned pivotal trial, you just recently announced that. Maybe discuss what's coming up for that.
Yeah, yeah. I mean, we have seen exceptional data. We published this at ESMO last year. Very good response rates, also deep responses, CRs, observed. And this was the basis for going into a pivotal trial, potentially starting later this year or not potentially starting, sorry, starting later this year. And this is a seamless phase II/III trial of HB-200 plus pembrolizumab versus pembrolizumab monotherapy, which is the standard of care in CPS 20+ oropharyngeal squamous cell carcinoma. 250 patients will be enrolled 1:1. There will be a phase II interim readout at approximately 50% of the patients. And this is based on ORR with then the potential of an accelerated approval. We discussed this protocol and also the design with the FDA. We met the FDA. We aligned, and they agreed on the design. And we can start, and we are in the setup phase.
The confirmatory part, the phase III part, there, the primary endpoint is overall survival but is independent of the phase II part and comes later after the phase II readout.
OK, great. And then the ORR result, maybe you said it, readout expected for the phase 2 in 2026. Any interims ahead of that? Any biomarker immunology data that we can track? And what's the plan for Europe with the program?
Yeah, first of all, we will be at ASCO. We will have an oral at ASCO at the head and neck HBV positive specific session, which is also remarkable that there is, in the meanwhile, such a dedicated session showing that there is a high unmet need specifically for HBV positive disease. We will report data on an update of approximately 40 patients from the phase II in combination of pembrolizumab. We will also report some early durability data, preliminary PFS, and overall survival. As said, this was the basis for our phase 2, phase III trial. What was the second part again?
Europe, sorry.
Europe, yeah. So we started with the U.S. in terms of protocol review, getting alignment with the FDA. So this is all set. But you may have seen, we also got the Prime designation from Europe. So we are in the process of talking to Europe as well and will start the trial. It's a multi-regional trial, Europe, U.S., but also other regions. So the trial will be in Europe. And then after submitting the data, if positive in the U.S., we will also go for Europe in a potentially a bit staggered approach.
OK, great. And then sorry, maybe back to ASCO. The readout, you said 40 patients. I think that's about a doubling over what you've presented before. And just yeah, what data can we expect there? T cell data, how many patients, and other biomarker data?
Yeah, from the majority of the patients, we have T cell data. We want to confirm at ASCO what we have seen before in the 20 patients, now with 40 patients in terms of T cell response, in terms of ORR. We would like to see deepening of the response. Watch for the CR rate. Watch for the durability of the responses and preliminary progression-free survival and overall survival as well. Of course, as our registration strategy is the CPS20 and above population, we will zoom into this subpopulation and present the data there as well.
OK, great. Can you remind me how many patients? Well, you probably haven't said for the 40, but about how many patients are going to have CPS above 20?
50%.
50%, OK.
50%.
And maybe, yeah, describe that strategy a little bit more, why you went with that. I mean, it makes sense, obviously, but what in the data that you saw before led you to that CPS cutoff?
Yeah, 50% of the patients CPS 1-19, 50% CPS 20 and above. We saw a benefit in the overall population, but it was more pronounced in the CPS 20 and above population. And so this is also highly biologically plausible because in tumors where you have a higher PD-L1 expression, you usually have also a better T cell infiltration. But the T cells which infiltrate in pembrolizumab are sometimes exhausted, not active, not tumor specific. And this is what HB200 does. It activates the T cells. It leads to a high number of T cells. They go effectively into the tumor. And then you have the synergy with taking off the brake by pembrolizumab with pembrolizumab. And this led to the synergy. So we have a high biological plausibility and really differentiated data if we look at these two subgroups.
Importantly, this gives us a very quick path to approval. An accelerated approval based on ORR is possible, which may be difficult if you go for the overall population. It's the patients with the best probability to then get the drug to them first. We will, of course, look also at the other populations as well for a development path.
OK, so for a short time, you're maybe not addressing half the market, but you increased the probability of success more than that, likely.
Yeah, maybe a comment here. But you say half the market. So the market usually is patients you treat but also for how long you treat them. So if you look even at pembrolizumab monotherapy, but in particular our combination, you see that the 20-plus population has a higher overall duration of treatment. So I would make the point that it's significantly more than half of the market. Or so you're correctly saying it's half of the population.
Right, yeah. And if you get there earlier, I mean, what's the PRV worth? $100 million? So if you get to the market six months earlier, you're making more money there, right? And treating more patients. OK, great. Maybe can you talk a little bit more about the plan for addressing this under CPS 20 patients? Are you going to wait and see how this trial reads out and then go there? What's the plan there?
Yeah, exactly. So the phase II is still ongoing. We are actively still enrolling patients also for 1-19. We want to see a little bit more patients in the segment of 10-19. We have seen 1-10, but we also want to see 10-19 and then decide what the best, smartest development strategy for a supplementary BLA would be. There are different options, which we are currently discussing. It will be, again, data-driven. And in the whole context of the phase II/III trial, we will find a way in discussion, of course, with the agencies.
OK, do you think you might announce some of that data later this year from the under 20 patients?
We will have data at ASCO. But you are right. It's maturing. We are continuing to enroll. And then most likely at a later point in time, I can't say if this will be the end of this year or beginning of next year and in which format we will give a data update.
OK, all right. And then you also have some efforts in adjuvant and neoadjuvant setting. Maybe just update us where those are at and what your plan is.
Yeah, this is, I mean, a setting which has a great potential as well. We are active in this setting. What you will see, we have a second oral at ASCO for our IST with the University of Chicago in the neoadjuvant setting for local regional head and neck. They will present the first results in the rapid oral session. This is really great and will inform also us what the next development steps will be in this setting. MSKCC just posted a few weeks ago on ClinicalTrials.gov our IST in the adjuvant setting in MRD positive head and neck cancer after curative treatment. This will also inform our development strategy in the adjuvant setting. We are very happy that we are active there and find a path.
OK, all right, great. Manufacturing, where are you at with manufacturing? Do you make the virus yourself? What are the plans for commercial scale? Is it difficult to manufacture?
Yeah, so obviously, it's not trivial to manufacture a gene-modified live virus. So a core competence of HOOKIPA is process development. And we have actually found a very viable and efficient process that we have upscaled appropriately so that we can say today, manufacturing is solved. We have the product ready to be used in the phase II/III trial. And while the trial is ongoing, we'll make the necessary adjustments and documentation and assays also for commercial production. While we have a lot of know-how and control the manufacturing process and have developed it in-house, we do not have a GMP manufacturing facility. So we rely on external CMOs to manufacture the drug for our clinical trials and probably in the future for the commercial market.
OK, all right, great. All right, very exciting. Sounds great. Well, I guess maybe competitive landscape for head and neck. PDS recently announced some plans for phase III. Anything that you're watching, anything particularly interesting that we should keep an eye on? Or even more broadly in cancer vaccines? I just pick your brain, Mark, a little bit.
Yeah, yeah, I mean, we are watching the same as you. You are watching. The field is very active and developing. For us, it's a validation that the approach is valid of a combination of a cancer vaccine in HBV positive disease with pembrolizumab. The data others are showing are interesting. You see it that we have, as I said, a dedicated ASCO session for HBV positive head and neck cancer. And yeah, we are very proud that we showed excellent data in T cell response clinical activity, which we think has the best-in-class potential and also first-in-class potential because we are on a registrational path already. But we see it positive that the competitive field is so active. It validates the approach. The community is recognizing it. The medical community is recognizing it. And now it's about being quick in the development and executing.
Great, all right. Sounds good, yeah. Don't delay timelines. All right, sticking with cancer, but maybe move on. HB-700, I know this. So KRAS, which seems like a great candidate to me. Roche had it. They gave it back, I guess. Why did they decide not to pursue the candidate? And I know you submitted the IND. You got a $10 million milestone. What are the plans from here? And yeah.
Yeah, so the termination by Roche came somewhat as a surprise because we met all the collaboration goals. We hit all milestones. But it happened for strategic reasons. And that happens within big companies. And there was, I think, a major reprioritization within Roche that affected our project but also others. So we think we regained the rights for a very interesting potential drug. Our near-term focus is on getting the 200 pivotal trial kicked off. But I think we do own the asset. We have the IND cleared. We received a $10 million milestone from Roche for the IND clearance. So we will continue to develop that product, although probably not with the speed that we would have done in the collaboration with Roche.
OK.
If I may add, so we are actively talking to KOLs, to physicians, how a smart development path could look like for HB-700. Also here, I think it's very visible that the KRAS mutation field is developing so quickly, majority inhibitors, not so much cancer vaccinations. But I think that this can be an absolute component to get to a big step in KRAS mutated cancer. So HB-700 would have a great potential here.
OK, great. All right, looking forward to it. All right, talk a bit about infectious disease. So Reinhard, you mentioned the hepatitis B and HIV programs. Hepatitis B still remains one of my favorites. I think the T cell power can be really important there. I guess just so Gilead's running the phase Ib for hepatitis B. Do we have any sense of when they might give us an update? I know they have presented some non-human primate data, but.
Yeah, and the non-human primate data was excellent. As you said correctly, the phase I is run by Gilead. So they control the timelines. I think the trial is progressing very well. But I can't comment on when Gilead plans to release any data.
OK, and you probably can't comment on this either. But any indications they might combine it with their other agents?
Yeah, it's important that this program is part of their broader HBV cure program. Anyone knows that Gilead is maybe the most well-positioned company to work on an HBV cure. It's a difficult goal to achieve. It will require a combination of multiple drugs. You see within the Gilead portfolio that clinical trials are ongoing for different immunomodulators, other modalities. It will probably take a combination of two or three drugs to hopefully be able to cure that chronic infectious disease over time. We have to say we believe, and Gilead believes, that T cell therapy is a cornerstone of these combinations. I think our technology has shown that we can bring those target-specific T cells to the table of a future combination regimen.
Yeah, agreed. OK, great. And then HB-500, that's an HIV cure, also partnered with Gilead. But you're running the phase Ib. Where is that at?
Yeah.
HIV vaccines have been a pretty tough field, right? Obviously, how do you think you can be different here?
Again, it's a combination. It requires a couple of steps of kind of reactivating the reservoirs and then directing T cells against them. Again, T cell therapy and really high levels of T cells have been a challenge for all vaccination approaches. And we know prophylactic HIV vaccination has been a big challenge, but mostly antigen-modulated. When Gilead was looking to set up their combination programs, they were specifically looking out for a technology that has the best potential to get the T cells to really the high level that may be needed to have an effect in patients. And again, this is what we bring to the table. You mentioned the phase I. Just briefly, we got the IND cleared. We are actively activating the sites. And still in Q2, we'll dose the first patient.
OK, great.
Yeah, and if I may add, so because you said vaccinations have not been successful, unfortunately, this is true for preventive vaccinations. Here, it's a different approach. We want to eradicate infected cells, the residual cells after combination treatment in HIV. We want to eradicate with a T cell approach. This is the novelty here.
OK, is there animal evidence that that's a viable approach?
Yeah, we've shown data in non-human primates where we were able to reduce the viral loads.
OK, OK, great. All right, any questions from the audience? Anybody? Yes?
Jake.
It's a pretty small room. I would think of vaccinations, like you'll get a flu vaccination. You'll get a normal to help prevent. In some diseases, I guess, treat. You want it HIV, you're talking about that. But for cancer, you're working in combination. Are you looking to just advance? What's the goal here? Is it ease of use? Is it like the treatment? Or is it just because these combination therapies, they add months maybe to people's lives, expand the populations? Is that what you're just trying to do, is just advance the current cancer treatments by months and treat more people? Or is this supposed to be some sort of radical advance on how?
Radical, radical, radical. I mean, I mean, pembrolizumab, for example, leads to a cure rate, so to say, a cure rate even in last-line settings, about 10% or so. And we want to unlock the potential more of the combination, going up to, I don't know, 20% and in other combinations, even more. Plus, then moving to the earlier settings, which is adjuvant, neoadjuvant, and increase the cure rate here as well. So it's not about, OK, prolonging a few months, but really eradicating residual disease, which would be adjuvant or neoadjuvant, or even in the metastatic recurrence setting, in combination with immune modulators, getting the tail of the overall survival pembro curve up to say we can achieve in the combination a higher fraction of patients which cured or at least long-term, several years, survive longer. That's the goal.
Wouldn't you see that in phase I?
In our development?
With ASCO
Yeah, I mean, that's what we're seeing. I mean, you will see at ASCO data about the durability. This is what we are hoping for, that we have long-term durability. At the end, can, in our phase II/III trial, compare, let's say, 2 years, 3 years, 4 years fraction of long-term survivors, pembro mono, versus HB-200 plus pembro?
What is it in the stock that investors aren't recognizing if you've already shown that?
Well, we are in the process of showing it. We have hints and signals that this is working well and has a high potential. But of course, a randomized trial needs to be in place to show it. This is what we are doing.
Thank you.