Innate Pharma S.A. (IPH) Earnings Call Transcript & Summary

Hi, everyone. Welcome to the 43rd Annual JPMorgan Healthcare Conference. My name is Luka Kachukhashvili. I'm an associate here in the health care IB team. Absolute pleasure to introduce Jonathan Dickinson, CEO of Innate Pharma.

Thank you, Luka, and good morning, everybody. I'm very thrilled to be here to present on behalf of Innate Pharma. I'm joined today by some of the leadership team here from Innate Pharma. So I have Yannis Morel, who's our Chief Operating Officer. He's been with the company for -- pretty much since the beginning and has been driving our scientific excellence and responsible for some of the great BD deals that we've done with AZ and with Sanofi. We also have Sonia Quaratino, who's our CMO. Sonia is a very experienced CMO. I think this is her third CMO role after a couple of successful exits. And prior to that, she was in big pharma and prior to that, a Professor of Immunology. We also have Arvind Sood, who's our Head of U.S. Operations. And Arvind joined us just over a year ago from Amgen, where he was for over 20 years, I think, mainly running IR. So let me get into the presentation and starting off with the standard disclosure statements. And really, first of all, talking about Innate Pharma. And I guess I was recently appointed to the role in November last year. And there are a number of reasons why I chose to join Innate Pharma, and I think they're captured in this particular slide. So Innate Pharma is a world leader in proprietary monoclonal antibodies and in particular, in NK cell engagers. Based on that expertise, the company has moved in a couple of directions. We have what we call our ANKET platform, which is our NK cell engager platform, and this is a proprietary platform. We also have been focusing on antibody drug conjugates. And we've used that proprietary antibody expertise to engineer what we believe are very differentiated ADCs that have the opportunity to make a significant impact in the market. So just reflecting on our year-end 2024, it was a very strong year from an Innate Pharma perspective. I think it's reflected in the quality of the science and the publications that we put out in 2024, and you can just see here some examples of some of the world-class science that was taken forward at Innate and published in very high-impact journals like Nature. We also had a very successful year from an R&D perspective with a number of critical milestones, which we managed to achieve throughout the year. The first of those is around our lead proprietary asset, lacutamab. Lacutamab went through an interaction with FDA towards the end of the year. That was a very successful interaction. We basically aligned with FDA on an accelerated path to approval for lacutamab and the high-level elements that will be required in terms of a confirmatory study, to support that opportunity. So a big success from lacutamab perspective. We also initiated a Phase I study with our lead proprietary ANKET IPH6501 in non-Hodgkin's lymphoma. So another very important milestone. And then towards the end of the year, we had the IND cleared for IPH45, which is our lead ADC molecule. So moving into 2025 and our future focus, we basically have refined our strategy, and we're focusing on 3 key pillars to drive the future of Innate and to drive the future growth of the company. The first 1 of those pillars is the ANKET platform that I described earlier. And you can see here a number of assets listed within that column. The first 1 being the IPH6501, which I mentioned earlier. The second one is IPH6101 and this is and ANKET, which is basically targeting CD123. This is licensed to Sanofi. And Sanofi has taken this asset forward. So this asset completed during 2024, a Phase I study in treatment refractory AML patients. The data was presented at the European Hematology Association Meeting last year. Showed a very good response rate in these treatment refractory patients of 33%. And off the back of that, Sanofi took this asset forward into a Phase II study in treatment refractory patients and has also initiated a Phase I study in combination with Venetoclax and Azacitidine. So that's exciting. We also have a have a second ANKET, which is in the clinic and moving forward with Sanofi, and that's IPH6401. This is an ANKET that targets BCMA and is being investigated in a Phase I study in multiple myeloma. So that's the first pillar. The second pillar is around our antibody drug conjugates. And the lead asset here is IPH4502. This product cleared the IND. And hot off the press, we expect to recruit the first patient into the Phase I study in January this year, so in the coming weeks. We also have a second ANKET -- sorry, ADC, IPH43, which is targeting MYC Ab, which is in preclinical stage. We then have our third pillar, which is our late-stage assets. And this is led by lacutamab, which I mentioned in the first earlier slide, which has gone through this step with FDA in terms of establishing an accelerated path to approval. What we're now looking to do is to find a partner for this asset so that we can basically aggressively move forward the Phase III program and bring this product to patients. The final aspect in that column on our late-stage assets is monalizumab. Monalizumab is a product that is partnered with AstraZeneca. This particular product is in late-stage development. It's actually in a Phase III study called PACIFIC-9 in combination with AZ's durvalumab. That study is fully recruited. It's gone through an interim analysis, and the results from that Phase III study are expected sometime during early 2026. So there are 3 strategic pillars. If we look at our pipeline, you see a very extensive, multifaceted pipeline of differentiated and proprietary assets as well as partnered assets. We actually have 7 assets in the clinic today. through partnership or as proprietary. We will have the eighth product coming into the clinic in the coming weeks. So a very exciting portfolio and a lot of opportunities to drive the future growth of the company. So what I'd like to do now is focus a little bit more on each of those pillars and give you a little bit more detail and flavor for each of them. So the first one is our ANKET platform. So this is our proprietary NK-cell engager platform. This is a platform that is really based around targeting CD16 and NKp46 on NK cells. The NKp46 is the critical component there -- here because this is conserved on tumor infiltrating natural killer cells. The mechanism of action is it basically facilitates natural killer cell mediated killing. It boosts the immune cell infiltration and boosts the natural functions of killer cells. The other critical element about this platform is that it's a very versatile platform. So what we're able to do is to switch out the tumor antigen on this particular platform. And I'll show you in the next slide a little bit more detail around that. So that we can target different tumor types with different ANKETs, and we're able to do that relatively quickly to produce a pipeline of natural killer cell engagers. And from an efficacy perspective, we have demonstrated in preclinical models, excellent activity of these NK engagers versus T cell engagers and demonstrated superiority over a CD20 benchmark. So that's exciting going into the clinic and leads to a lot of optimism around the product. So this slide basically gives you a little more detail on what the NK cell engager looks like. So we have the CD16 element. We have the NKp46 which is the critical element for binding NK cells in the tumor. And then we have the CD20 tag. This is IPH6501. So this is our product that we're focusing on targeting B cells. This asset has been taken to another level because what we've been able to do here is to make this into a tetra-specific antibody. And what we have done is engineered a non-alpha IL-2 variant into the antibody. So what we're aiming to do with this is basically to stimulate and to proliferate NK cells at the site of the tumor. So that's exciting. And as I said earlier, this product is already in the clinic in Phase I, and we're aggressively moving it forward. The first patient in that Phase I study for IPH6501 was recruited back in March. We're going through dosing cohorts at this point in time. So the study is actively recruiting and we'll be hoping to share some data later in the year or early next year. Coming back to some of the benchmarks of IPH6501 versus T cell engagers, you can see here on this slide, we illustrate a couple of key points in terms of taking this product forward. The first one is around B-cell depletion. So what we can see on the left-hand side of the slide here, is how effective IPH6501 is in depleting B cells versus a T cell engager. And you can see here that it demonstrates superiority in depleting B-cells, which has led to the excitement and the optimism in taking forward this product. The other critical element is illustrated on the right side of the slide, where you can see that we have less effect on pro-inflammatory cytokines. So this means basically that we have less potential to generate cytokine release syndrome, which from a safety perspective when we get into the -- when we're in the clinic, could be very important. And this could be a very important differentiator if we decide to take this particular asset into the autoimmunity space, where the safety aspect would be critically important. The -- this asset has actually been generating a lot of attention from a number of stakeholders, and I've given you one example here that reflects that interest. We have had the IFLI follicular lymphoma charity, take a significant interest in the product. They see a lot of potential in the product. So much so that they've decided to invest up to $8 million into an equity stake into the company. And again, I think this reflects the science and some of the optimism and excitement about this particular target and where we can potentially take this particular asset. So what are the next steps? So what we'll be looking to do is to demonstrate preliminary safety and efficacy data sometime during this year or early next year. We'll be then going into the dose optimization phase subsequently in 2026. And then we will be looking to combine this product with standard of care in taking it forward as an exciting opportunity in B-cell lymphomas. But we also, as I mentioned earlier, have the opportunity to also pivot into autoimmunity. And we believe this could be a very exciting opportunity for autoimmunity or an asset for autoimmunity based on the hypothesis that we will see a much better safety profile than T cell engagers which are being used in autoimmunity. So that's our first pillar. The second pillar is our antibody drug conjugates. And you can see here a schematic of our lead ADC, IPH4502. So this is a proprietary asset for Innate. The secret sauce with this product is really based around the epitope and the antibody engineering. We've been able to engineer this antibody in the epitope so that it not only binds highly expressing Nectin-4 expressing tumors, but it also binds low and moderately expressing tumors. And this creates a significant opportunity for us. We're also using a different payload than PADCEV which is approved in bladder cancer. We have an exatecan payload. And this has -- obviously has a different profile to MMAE. What we see, we've been able to achieve a DAR8 with exatecan with this particular asset. And what we see here is a very significant bystander effect which I'm going to demonstrate in some of the next slides. From a linker perspective, we have a very hydrophilic linker. It's very stable. We see very -- very little of [ free ] circulating exatecan. So that's excellent from a safety profile perspective, and we have excellent conjugatability. So that means it's reasonably easy to manufacture, which is not always the case with ADCs, and we believe that, that could also be a competitive advantage. So coming back to what I was talking about on the left side of this slide, you can see the different tumors, which express Nectin-4 at various levels. We know PADCEV is approved in bladder, where most of bladder has very high expression levels of Nectin-4. You can see that there are some other very significant tumor types that have moderate or lower levels of expression of Nectin-4. So this is where we believe we have an opportunity for IPH4502. There's some very big tumor types there like triple-negative breast cancer, non-small cell lung cancer, prostate cancer. So as I said, an exciting opportunity moving forward. And what I want to do now is give you some more -- a few details of why we're excited about IPH4502. And I think this first slide shows you the activity in preclinical models of IPH4502 versus EV. And you can see in high-expressing tumors, we see excellent levels of efficacy. You can see in moderate expression, we also continue to see excellent levels of activity and also then in low expressing tumors on the very far right of the slide. And you see here that this is where EV does not work in the lower expressing tumors. So this gives us excitement and it opens up this basket of tumors where we believe we can develop this product and show some significant differentiation. We also have demonstrated that this particular product, IPH4502 has activity in heterogeneous expression of Nectin-4. And this is based around the excellent bystander effect, which I mentioned at the beginning -- earlier in this particular section. And you can see this is demonstrated in this slide where we're able to basically produce a model which mimics heterogeneous expression. You can see that on the very far right side of the slide, where we can see that we have excellent activity in this particular preclinical model even in heterogeneous expression. The other area where we believe there's an opportunity for IPH4502 is also in PADCEV resistance or EV resistance. So we've been able to generate an EV resistance model. And what we have shown here is that in EV resistant samples. Basically, we are able to demonstrate significant activity, which you can see on the right side of the slide, where EV does not continue to work. So again, this gives another opportunity to take forward this product in a PADCEV resistant patient population. This could lead to a very accelerated approval, a very fast track development program in this particular group of patients who have very limited treatment options after they've received PADCEV. So again, something that we're very excited about. So if we look -- next steps again here, it's about starting the study. So as I mentioned at the beginning of the presentation, we expect the first patient to be recruited into this -- the Phase I study in the coming weeks, so sometime during January. We expect to then relatively quickly be able to generate safety data and to be able to demonstrate some early signs of activity. We will then be looking to optimize the dose as we go into 2026. And then to start trials in -- a basket trial in combination with standard of care to demonstrate the differentiation of this particular product. So again, another exciting element -- pillar of our strategy as we're moving forward. The final pillar is around our late-stage assets. And the first one of those is lacutamab. So this is an anti-KIR3DL2 targeting antibody which has been in development for cutaneous T-cell lymphoma. So that's Sezary syndrome and mycosis fungoides. We have completed a Phase II data -- a Phase II study called the TELLOMAK study in Sezary syndrome and mycosis fungoides. And the data from this was presented at ASH '23 and ASCO 2024. This product has been recognized and has FDA Fast Track designation and EMA prime designation. It also has orphan drug status for the U.S. and for Europe. And as I mentioned at the beginning, we now have this potential path to accelerated approval for Sezary syndrome with FDA, which we now need to put in place a Phase III to take advantage of. If we look at the data and just give you a snapshot here, you can see that we demonstrate excellent efficacy with lacutamab in Sezary syndrome, in heavily pretreated patients. These are patients with 5 median lines of prior therapy. And you can see we see excellent responses. And I think the waterfall plot on the right side of the slide really demonstrates that most patients benefit from receiving this particular product. I think the other exciting thing is that everything aligns, including the translational data, the health-related quality of life outcomes aligned with -- very nicely with the efficacy data. So we feel we have a very derisked product moving into Phase III, where we expect to see a positive outcome when we move into that Phase III study. In mycosis fungoides, you see a very similar effect. The difference here is we did a diagnostic test moving into this to basically have a cohort of highly expressing -- patients who highly express KIR3DL2, and a cohort of patients that are low expressers. What we saw in the study is that we see activity in both low and high expressers. So this is actually excellent news. It means that in the confirmatory study that we've aligned with FDA that we can do an all-comer study. We can retrospectively test for KIR3DL2. And this makes it basically easier to do the study, and it increases the potential business case or business opportunity for lacutamab. So exciting data. So I think this slide illustrates that business potential. So on the left side, you see basically, if you were going in Sezary's alone, it's a relatively small business opportunity, but with a very high unmet medical need, which allows for the accelerated approval. We saw the diagnostic cut. Where we are now is we're moving to the right side of the slide because we've aligned, as I said, with FDA. So we don't need to do that diagnostic cut going into the confirmatory study. We've also aligned with FDA that we can do the confirmatory study in an earlier line of therapy -- sorry, as earlier line of therapy, so we can go after 1 prior line of therapy rather than after a minimum of 2 in the previous study. So that takes the business potential from around 1,500 patients that we've been looking at previously now to a business case of over 5,000 patients, which means that there's an opportunity well in excess of $500 million, probably somewhere in the region of $500 million to $700 million for this particular asset. So next step, we're in partnership discussions for this particular asset with some midsize pharma companies, and we see a good level of excitement about the product. So we're quite optimistic that we will be taking that forward into a partnership. We will also be working on a BLA and the accelerated submission and also initiating the Phase III study -- confirmatory study, which we will need to have in place to be able to -- and ongoing and having recruited a good number of patients to be able to take advantage of the accelerated approval opportunity. And then the final piece on there is one that I haven't mentioned before. There is another opportunity for lacutamab and that's in peripheral T-cell lymphoma or PTCL. This is actually a much bigger opportunity. It's around 19,000 patients. And this is something that we're investigating in a Phase II study called the KILT study, where we would expect to have data sometime during 2026 and could lead to a very interesting life cycle opportunity for lacutamab. So that's lacutamab. The second component, which I mentioned at the beginning was monalizumab. Monalizumab is our NKG2A targeting monoclonal antibody. This is in the partnership with AstraZeneca. And this based off the back of 3 positive Phase III study -- Phase II studies was advanced into the PACIFIC-9 study. This study, as I said earlier, is ongoing. It's fully recruited, past the futility analysis and we're expecting the primary results sometime in 2026. So that's another exciting card that we will be turning from an Innate Pharma perspective. So that's our strategy, our 3 key pillars that we will be pursuing moving forward. From a news flow perspective, I've mentioned this, but just to recap, we're expecting data on our ANKETs, in particular, 6501, where we will have some safety and preliminary efficacy data. Similar, we will start our ADC 4502 in 2025. And then we will take some steps forward with lacutamab, including partnering, initiating the Phase III plans and PTCL data coming slightly later. In 2026, we should have the full clinical data from the Phase I study. We have also then the safety and efficacy data coming from IPH4502, our Nectin-4 target is ADC and the accelerated approval submission for lacutamab. And then we have a number of milestones associated with our partner products on 6101, 6401 with Sanofi. And then, as I mentioned, PAC-9 with AZ. We also have another product with AZ, which is an anti-CD39 IPH5201 where we expect a Phase II data readout as well. As well as further options on our ANKETs from Sanofi. So a healthy news flow going over the next couple of years. So to conclude, we have a strong strategy in place to take the company forward. We believe we're going to deliver very strong growth moving into the future. We have 7 clinical assets today and eighth one coming in the next few weeks. We're driving forward our ANKET portfolio with IPH6501 in B-cell lymphomas. The -- we have the ANKETs with Sanofi moving forward, in particular, 6101 in AML. We're pursuing a very differentiated strategy for our ADCs and in particular, our lead ADC 4502 with the opportunity in low and moderate expressing tumors as well as PADCEV-resistant. We have lacutamab, which is a Phase III-ready asset with an accelerated approval pathway with partnership discussions ongoing. And then we have monalizumab with a key milestone and card to be turned, which will be obviously very important. From a cash position, we have cash, which -- on an audited basis, which takes us to the end of 2025. And we're working on a number of initiatives, which need to be audited, but we'll take our cash runway well into 2026. So on that note, I'd like to stop and open up for questions.

Thank you very much, Jonathan, for the presentation. I can kick it off and then pass it around to the audience. You were recently appointed CEO of Innate Pharma. I was wondering if you could speak about your background, why you decided to join the team and just kind of your vision for future growth of the company.

Yes, I can. Yes. Yes. So my background. So I have over 30 years' experience in oncology. Most recently, I was the Head of Region Europe for Incyte. I've been in that role for 8.5 years, launched 3 oncology drugs and then a product in autoimmunity in dermatology and basically decided after 8 years, I needed a new challenge. Prior to Innate, I worked at ARIAD, a small biotech, and I initiated the European operations for ARIAD and built a commercial organization in 16 countries from the ground up, which was actually then acquired by Incyte, which is why I ended up at Incyte. Prior to ARIAD, I was at Bristol-Myers Squibb for 3 years. I led the commercial immuno-oncology franchise. I had P&L responsibility for Europe and launched Yervoy (ipilimumab) and did some of the early work on nivolumab. Prior to that, I was at Hoffmann-La Roche for 14 years. I had positions of life cycle leader, so I worked on Xeloda capecitabine in breast cancer, colorectal cancer and gastric cancer. In that role, you're the GM of the product, you touch everything from basic research all the way through clinical development, commercialization, supply chain, regulatory. Prior to that, I was the global brand leader at Roche for Herceptin and launched Herceptin in breast cancer in the first indications globally. Prior to that, I was the global brand lead for Rituxan and launched Rituxan in the first indications. And before that, I was in the U.K. at Novartis as the business unit head for oncology and endocrinology. Prior to that, I'm a scientist, a molecular biologist with an MBA. So I think all of that skill set sets me up with lots of experience in oncology and developing drugs, but also in commercializing drugs to really take Innate Pharma to the next steps. And I think from a next-steps perspective, we need to basically take our drugs further along the development pathway ourselves rather than partnering them out at a very early stage, so we can really realize the full value of those assets. And yes, and eventually, in the longer term, my hope is that we could turn Innate into a commercial organization. That's not something for the short or midterm, but in the longer term, that would be our aspiration.

Thank you for that, definitely a distinguished career up until now. And best of luck in the future. Regarding lacutamab, I was wondering if you could speak a little bit more detail on your regulatory pathway, any recent interactions with the FDA and just any more details there.

Yes. So maybe I will hand over to Sonia or Yannis to basically say a little bit more about it because I think I gave an overview. It would be good to -- for you to see some of the leadership team in action and Sonia, I don't know if you want to say a few words?

Certainly. We recently had an FDA interaction. And basically, the main points out of this interaction is that we had an endorsement from the FDA that the data produced in the TELLOMAK study in Sezary syndrome for patients that received prior therapy with mogamulizumab, so patients that have no approved drugs ahead of them. The clinical results are competitive enough to go for an accelerated approval. So this is the first, let's say, important outcome of this interaction. The second important outcome is that the FDA agreed that the dose that we intend to bring to Phase III is appropriate. And so as you know, after Project Optimus many drugs had been questioned about the dose for subsequent studies. And so this is something that we had dissipated from there. The third outcome of importance is that the FDA agreed that we do not need the use of a companion diagnostic for mycosis fungoides considering that patients might express more or less of the target. And the fourth outcome is to have some guidance on what is let's say, need to be seen in the Phase III ahead of us and to go in an earlier line. And so in that respect, we can conclude we have really a Phase III-ready asset and we had also very useful guidelines from the FDA on what this -- what items need to be considered.