Innate Pharma S.A. (NASDAQ:IPHA) Q2 2024 Earnings Call Transcript

Innate Pharma S.A. (NASDAQ:IPHA) Q2 2024 Earnings Call Transcript September 12, 2024

Operator: Thank you for standing by, and welcome to the Innate Pharma First-Half 2024 Financial Results and Business Update. All lines have been placed on mute to prevent any background noise. After the speaker’s remarks, there will be a question-and-answer session. [Operator Instructions] Thank you. I’d now like to turn the call over to Henry Wheeler, Vice President, Investor Relations and Communications. You may begin.

Henry Wheeler: Thank you. Good morning, good afternoon, and welcome everyone. This morning Innate issued a press release for our H1 business update and financial results. We look forward to highlighting the progress made during the year-to-date, as well as addressing future goals and milestones. The press release in today’s presentation are both available on the IR section of the website. On slide two, before we start, I’d like to remind you that we’ll be making forward-looking statements regarding the financial outlook in addition to regulatory and product plan developments. These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted. On slide three, on today’s call, we will be joined by Herve Brailly, our Interim Chief Executive Officer.

We’ll then hand over to Sonia Quaratino, our Chief Medical Officer, who will cover updates on the lacutamab and IPH65. We will then hand to Yannis Morel, our Chief Operating Officer, who will discuss ANKET and the ADC platform updates; Frederic Lombard, our CFO will cover the financials; and Arvind Sood, our EVP, U.S. Operations will wrap up and close. Herve I’ll now hand the call over to you.

Herve Brailly: Thanks, Henry. So turning to slide five, I’d like to remind you of an Innate Pharma Strategy. So now there’s an early stage clinical stage strategy. All business model centers around three priorities where we look to draw value from our early R&D efforts through later stage partnerships where it makes sense to do so. Our ambition is to develop innovative drug candidates with a strong pipeline of differentiated antibodies. So first we look to create near-term value driven by our lead proprietary asset, lacutamab, in development for T cell lymphoma with topline CTCL data that were presented at ASCO this year on ASH in December. We’ll do latest data in hand, we’ll now assess the best path forward to maximize the potential of this asset.

Second, we continue to fuel a pipeline and create longer-term value by leveraging on our antibody engineering capabilities to develop innovative molecules with a primary focus on our multi-specific end-case elongation platform ANKET. We are pleased to see continued progress with Sanofi, presenting various updates for the lead ANKET candidate, SAR443579, which was recently transitioned from Phase 1 to Phase 2 in monotherapy, and more recently has started a new combination Phase 1/2 trial. We’re also pleased to see our lead candidate ANKET IPH6501, continue in Phase 1. As we develop antibody targets, we recognize some of these targets might be very suitable for ADC technology. And we have some further details in our ADC pipeline today with our lead ADC asset IPH45, progressing through Phase 1.

Finally, we are building a strong foundation for business by key partnership across industry. On a key example there is monalizumab where we saw some further data, Phase 2 data presented last week at WCLC, which is partnered as you know with AstraZeneca on its advancing in its developing lung cancer. The next slide, that is slide six. Slide six summarizes actually where we stand with our pipeline and shows how we continue to translate our science into a robust portfolio of proprietary unpartnered assets. It also illustrates how we are executing against our strategy with our lead proprietary assets lacutamab, ANKET on emerging ADCs supported by partnered product with a AstraZeneca, Sanofi and Takeda from late to early stage development. We actually anticipate a series of potential clinical data readouts on catalysts in the upcoming couple of years as our R&D engine looks to leverage our scientific know-how to create a sustainable business.

I’d like now to pass the call over to Sonia, who will review the progress made with a portfolio, starting with lacutamab, our most advanced proprietary asset.

Sonia Quaratino: Thank you, Herve. On slide eight, I will recapitulate the progress we are making with lacutamab and in particular with the TELLOMAK trial in Cutaneous T Cell Lymphoma. Lacutamab is a monoclonal antibody that targets KIR3DL2 and was shown to deplete the cells that express the receptor. Just a reminder, the KIR3DL2 is apparently expressed as a tumor-associated antigen in CTCL, in particular in more than 90% of patients with Sezary syndrome and approximately 50% of patients with mycosis fungoides. The TELLOMAK trial is a Phase 2 single arm study, investigating lacutamab monotherapy in CTCL in patients with Sezary and mycosis fungoides, who received at least two prior systemic therapies. The FDA granted an orphan drug designation for lacutumab in the treatment of CTCL and the first drug designation for the treatment of all patients with refractory relapsed Sezary syndrome who have received at least two prior lines of systemic therapies.

The key results of the trial in Sezary were presented last year at ASH. And At ASCO this year, we presented the key results in mycosis fungoides cohorts. We are going to present other secondary results at other conferences this year. Aberrant expression of KIR3DL2 is often detected also in peripheral T-cell lymphoma. And in this indication in PTCL, lacutamab is investigated in combination with gemcitabine and oxaliplatin. The KILT Phase 2 trial is currently ongoing and recruiting and we believe this combination with chemotherapy may offer additional benefit to patients with PTCL. In the next slide, I would like to summarize the key results in [MS] (ph), which were presented at ASCO annual meeting in June. In this heavily pretreated patient population with four median prior lines of therapy of systemic therapy and 11.8 months of follow-up.

At the data cutoff of October, 2023, we observed a global objective response rate of 16.8% and the median PFS of 10.2 months. It is interesting to stress that objective responses have been observed not only in the sub-population expressing more than 1% of the target, but also in the population expressing less than 1% of the KIR3DL2. This suggests that lacutamab may produce clinical benefit in MS, regardless of the KIR3DL2 expression and you can see this on the water-flow plot on the right-hand side. In keeping with previous results, also in MS, a very favorable safety profile was observed. On the next slide, we can see the opportunity for lacutamab in the treatment landscape. With potentially no need for a companion diagnostic, we believe that the number of CTCL patients that could benefit from lacutamab expands from 1,500 to 3,500 in the two plus line of therapy.

And this figure may even increase to 5,000 in an earlier line setting. Now, our aim is to ensure that lacutamab gets to patients, who need it as quickly as possible and to maximize the value, not only in Sezary, but also in the larger population of mycosis fungoides. We believe that there remains a critical unmet need for additional treatment options, in particular for relapsed and refractory Sezary and also in mycosis fungoides. Based on the strength of our data from the TELLOMAK trial, we are engaged with the FDA on a proposed registration strategy that could enable a fast-to-market approval. On the next slide, we would like now to switch gear to our most advanced property asset, IPH65, the tetraspecific antibody-based NK-engager therapeutic, the ANKET molecule, which is the first NK cell-engager to engage the tumor via a tumor-associated antigen and on the NK side engage two activating receptor, the NKp46 and CD16, as well as the inter-looking to receptor by an IL-2 variant.

Here called IL-2V. The innovative mechanism of action includes the IL-2 variant in the aim to induce activation and proliferation of NK cells in the tumor microenvironment. IPH65 is the first of this second generation ANKET targeting CD20. And we were pleased, as Herve already mentioned, to announce earlier in the quarter that IPH65 entered the clinic and the first-in-human study has started with the patient being dosed early in March. The trial is enrolling patients with relapsed and refractory B-cell, non-Hodgkin’s lymphoma and the study is running in the U.S., Australia and France. There are a few points here that I would like to highlight about this tetraspecific ANKET. The elimination of the CD20 positive cancer cells by profound activation and proliferation of the NK cells.

By stimulating that the NK natural function by the L2 variant, IPH65 has a bystander effect and can also cause the elimination of the CD20 negative tumor cells, thereby overcoming the tumor heterogeneity or loss of tumor antigens, which is sometimes reported in patients. The IPH65 format also addresses the common challenges of antibody associated with loss of CD16 by ensuring activation of intratumoral NK cells via the NKp46. Furthermore, this asset differs from allogeneic and cell — NK cell therapies, including CAR-NK, as it is an off-the-shelf therapy that drives the proliferation of the patient’s own NK cells and does not require any lympho-dipulsion as cell therapy. We have presented the preclinical data at the ASCO meeting this year showing that IPH65 depletes autologous CD20 B-cells from healthy donor with greater efficacy and lower induction of pro-inflammatory cytokines that the CD20 T-cell engager.

IPH65 also effectively and preferentially stimulates NK cell proliferation from PDMC of relapsed refractory non-Hodgkin lymphoma patients. And last but not least, the trial in progress of the Phase 1/2 study has been presented at the European Hematology Association Congress and ASCO in 2024. On the next slide, I would like to very briefly give an overview of the next steps for IPH65. Throughout the year, we plan to complete the dose escalation and we look forward for initial safety data, PK and pharmacodynamics readouts, as well as preliminary efficacy signals. Throughout CD26 and beyond, we will open the dose optimization part of the study to select the optimal dose and expansion cohort in non-Hodgkin lymphoma. And now I will turn to Yannis to cover other ANKETs and the AGC.

Yannis Morel: Thank you, Sonja. I will now highlight the two class of next generation antibody therapeutics on which we are focusing all our research activities, the NK cell engager of ANKET and the ADC. On slide 14, I draw your attention to our portfolio of ANKET, which has made significant progress during the last quarter. As you remember, our proprietary 13-class NK cell engager platform is a multi-specific plug-and-play technology made of antibody-derived building blocks aiming at engaging NK cells toward tumor cells by triggering the most stable activating NK cell surface receptor called NKP46. The interesting feature of this platform is that by swapping the tumor-binding portion of the ANKET molecule, it can produce multiple drug candidates, addressing a variety of targets in oncology, but also it can potentially harness NK cells to kill pathogenic cells in other disease areas like [AML] (ph).

Last quarter, Sanofi advanced the most advanced ANKET, TAR-579, to Phase 2 on the back of initial efficacy data showing single agent activity with durable complete responses in relapsed refractory AML patients. In addition, Sanofi started a new Phase 1/2 trial in front line AML in combination with azacitidine and venetoclax. We are looking forward to seeing further updates from Sanofi. Also, as mentioned by Sonia, we are very pleased to have our proprietary second generation ANKET in the clinic with the first patient dose with IPH6501 in March. Last but not least, we are putting a lot of effort to further expand this portfolio to additional tumor targets, including in solid tumors. Slide 15 highlights our growing portfolio of ADC drug candidates.

As we continue to develop next generation antibody therapeutics, we find that for some tumor targets, we can generate antibodies with good internalizing properties that are therefore more suited for ADC. On slide 16, I will now cover updates on our lead proprietary ADC, IPH45, which is targeting Nectin-4. The preclinical characterization of this drug candidate has been presented at a normal session at AACR in San Diego earlier this year, and I like the key differentiation feature of this product. Based on this data, we feel that we have a novel and differentiated ADC to target Nectin-4 in the broad panel of tumor indication on top of bladder cancer by overcoming the challenges associated with Nectin-4, MMAE, ADC, including Enfortumab Vedotin.

Here on the slide, we highlight the opportunity for IPH45 in Nectin-4 expressing tumors, especially in low to moderate expressors, beyond bladder, like breast, lung, prostate, and pancreas, where efficacy reported by Padcev is so far limited. Slide 17 is a summary of some of the data presented at AACR. In a nutshell, we show that IPH45 has strong antitumor efficacy in a variety of preclinical models, including one that are refractory to Padcev, because of high expression of MDA1, which is a [Indiscernible] transporter, a known mechanism of resistance to MMAE. Also, it has strong efficacy in patient-derived PDX models with low expression of Nectin-4, as shown in the graph in the middle of the slide, where Padcev does not work. With the favorable developability profile, including high yields of productivity, high in drug stability, and encouraging PK tox data in animal studies, we are progressing IPH45 towards the Phase 1 this year.

On slide 18, we summarize the next step of the program. As we are progressing towards Phase 1 this year, we are looking forward to generating preliminary Phase 1 safety data in ‘25, and then to establish an activity in Nectin-4 expressing tumor types with low and high expression levels. On slide 19, I would like to remind you of monalizumab, the anti-NKG2A we have licensed to AstraZeneca for oncology. On this slide, you can see an overview of the late-stage development of Monalizumab in lung cancer. Based on the Phase 2 COAST data, AstraZeneca started in May 22, PACIFIC 9, a Phase 3 trial evaluating the addition of either monalizumab or oleclumab to durvalumab in the unresectable Stage 3 non-small cell lung cancer patients, who have not progressed after concurrent chemo-radiation therapy.

We are encouraged to announce in today’s press release that over summer the independent data monitoring committee recommended the continuation of the Phase 3 PACIFIC 9 based on the pre-planned analysis. The AstraZeneca sponsored NeoCOAST-2 Phase II study is also underway in an earlier lung cancer setting, evaluating the addition of novel agents, including monalizumab, to durvalumab and chemo in the perioperative setting. Preliminary data was presented last week at World Lung, supporting the activity of monalizumab in this setting with 26.7% of technological complete responses and 53.3% of major pathological responses observed in 60 patients, which are numerically higher than the currently approved regimen. Together with COAST and NeoCOAST, these NeoCOAST-2 data provide a third proof points in a controlled Phase II study that monalizumab provides an additional antitumor activity on top of durvalumab in early learning.

I will now hand over to Frederic.

Frederic Lombard: Thanks, Yannis. Today, I will cover the highlights from the financials. Detailed tables are included in the press release we issued today. The key elements of Innate’s financial position and results for the six months period ending June 30, 2024, are as follows. Revenue and other income amounted of $12.3 million in the first-half of 2024, and mainly comprised of two elements: first, revenue from collaboration and licensing agreements which mainly resulted from the partial and entire recognition of the proceeds received from AstraZeneca and Sanofi; and second, governmental funding for research and expenditure for $4.1 million for the first-half of 2024. On the operating expenses side, we are reaching $38.7 million for the first-half of 2024, with 75% related to R&D and decreasing by 5%.

R&D expenses decreased by $2.4 million to $29.1 million for the first-half of 2024. This decrease is mainly due to lower personnel and other R&D expenses. On the G&A side, expenses have increased slightly by $0.4 million to $9.6 billion for the first-half of 2024. Lastly, cash, cash equivalents, short-term investments and financial assets amounted to $102.1 million as of June 30, 2024, sufficient to fund operations until the end of 2024 — 2025, sorry. I will now hand over to Arvind.

Henry Wheeler: Arvind, are you there?

Arvind Sood: Yes, can you hear me now?

Henry Wheeler: Yes, go ahead.

Arvind Sood: Okay. Excellent. Thank you, Frederic. A key value driver for any biopharma company is upcoming R&D catalysts that can contribute to long-term growth. And we have a number of them. Near-term, we are looking forward to engaging with the regulatory bodies over next steps for lacutamab. Programs coming out of our ANKET platform continue to advance as IP86101, targeting CD123 in hematologic malignancies and is partnered with Sanofi has recently progressed to Phase II. Our proprietary TETRA-specific ANKET that goes by IP86501 is now in clinical development. And as Yannis pointed out, our ADC targeting Nectin-4 is rapidly progressing towards the clinic. So I would like to leave you with a few thoughts. Yes, we are a small care biotechnology company, but we have a differentiated pipeline with several first-in-class opportunities.

We have seven products in clinical development with three that are proprietary and four that are partnered. Within the first-half of this year, we have made significant pipeline progress, as outlined on this slide. Our cash position, as Frederic pointed out, of EUR105 million through the end of June will enable us to fund operations well through the end of 2025. This is also, in many ways, a very special year for Innate Pharma. It’s our 25th year anniversary. To commemorate this special occasion, we will host an investor meeting in New York on October 3 and beginning at 8 a.m. Eastern time in collaboration with and at the Mount Sinai School of Medicine. I, together with the rest of the executive management team, will be there and look forward to discussing our advancing pipeline and strategy for growth and value creation.

We hope to see you all there. So with that, Rob, I’d like to turn the call back over to you, and we can open the call for Q&A. And if you can please review the procedure for asking questions. Thank you.

Operator: Certainly, we will now begin the question-and-answer session. [Operator Instructions] Your first question comes from the line of Rajan Sharma from Goldman Sachs. Your line is open.

Q&A Session

Rajan Sharma: Hi, thanks for taking mu questions. Just on the NeoCOAST-2 data we saw at well conference for lung cancer. They obviously looked to be a good efficacy signal with monalizumab, as you pointed out, but optically, at least it looked like the data [DXD] (ph) I mean that trial showed higher response rates. So just wanted to get your perspectives on monalizumab potential role in the setting and why there may be a reason for it to coexist with data DXD and potentially the PD-1 CTLA-4 bispecific that’s also in that trial that we’re yet to see data for. And then on kind of CEO kind of appointment. Could you just maybe talk about internal time lines there? And then related to that kind of absent permanent CEO, to what extent are you able to make key strategic decisions.

Going forward, such as the strategy with lacutamab? And then if I could just squeeze one in on the Takeda termination. Just wondering there if there is any data generated that could be informative to your development of the ADC program? Thank you.

Herve Brailly: Thanks for all those questions. I will leave the first one on Mona to Yannis then the one lacutamab to…

Frederic Lombard: Herve, I don’t know if you can hear us, but we lost the sound.

Sonia Quaratino: I don’t hear it either.

Frederic Lombard: Herve, can you hear us?

Operator: Ladies and gentlemen, we are experiencing some technical difficulties. Please stand by your lines will just on musical for a very short time. [Technical Difficulty]

Herve Brailly: [Technical Difficulty] first question on monalizumab on the NeoCOAST trial. And then Sonia will give more color on where we stand with lacutamab. I will take the third question about the CEO recruitment. Yannis?

Yannis Morel: Hi. Rajan, can you hear me?

Rajan Sharma: I can hear you.

Yannis Morel: Yes. Yannis, speaking. Yes, so I mean, like you mentioned the NeoCOAST data are really encouraging for monalizumab and they really show superiority [Indiscernible] priority of the PCR and NPR rate, compared to what is known for agent, for example. The study is run by AZ, and obviously, we cannot comment on the next steps. You may note also that only 60 patients have been reported, the trial enroll 72 patients. So we are really looking forward to see the final data, not also that these are preliminary the confidence intervals are overlapping. And yes, as of today, I would say the main message from this data is that it’s reinforcing the confidence that mona is having really a on activity of monalizumab in early lung.

Herve Brailly: Lacutamab, Sonia?

Sonia Quaratino: Right. Around lacutamab, we — as I mentioned in our discussion previously, we are engaged with the FDA on a proposed registration strategy to pursue a fast-to-market approval. And as you know, FDA operates a variety of programs to expedite approvals in serious conditions and pending feedback from the FDA, we believe lacutamab could benefit from one of these expedite approval. And we will, of course, provide an update in due course when this is available. In regard to the next step, you mentioned we are actively looking for different options, including partnership we do not exclude any possible development for lacutamab in CTCL. I hope that address your question.

Yannis Morel: Yes. And Rajan, with regard to your question on Takeda. You may remember this was a very early stage deal with Takeda, where we based on the preclinical data package, we licensed them a panel of antibody, which were really at the research stage. So it was a very early stage deal. This termination is really related to a strategic review on their side and the closing of the research side where the research was performed with this technology in this therapeutic area. So yes, there is really nothing to, I would say, to [Indiscernible] about this determination or the data generated during this initial work.

Herve Brailly: To your question on the permanent CEO, so the process is still ongoing, but we should be able to come back and inform the market in a reasonable time about where we stand with progressed in this direction.

Henry Wheeler: Okay Rob, let’s take the next question please.

Operator: Your next question comes from the line of Daina Graybosch from Leerink Partners. Your line is open.

Daina Graybosch: Hi, thank you guys for the question. On PACIFIC 9, can you give us any more details about what this interim analysis was by which the IDMC decided to go ahead and continue?

Yannis Morel: Hi, Daina. Yannis is speaking. Unfortunately, we cannot tell anything more than what we said, and neither AZ nor us. I mean, there was an interim pre-planned analysis. The IDMC looked at the data, and we basically get information AZ and us that the trial is continuing. So that’s basically it.

Daina Graybosch: And maybe could I — could you help us pin down timing when we might when you might come to the next interim or final analysis of PACIFIC 9? And also help us on timing of the regulatory interactions with lacutamab. I think we’ve been asking the same sort of regulatory questions many quarters now. So which quarter should we really expect to have a more concrete plan from Innate?

Yannis Morel: Yes. So with regard to the timing of the PAC 9, no, we cannot comment. I mean you know what is public is the ‘26 you mentioned on the ct.gov. If you use the original PACIFIC as a benchmark that the time between the final analysis and the first patient was three years. But again, AZ has not communicated any update on the timing for the availability of the final data. And with regard lacutamab, we are calling to have the interaction during the fourth quarter of this year.

Daina Graybosch: You put into interactions in the fourth quarter. Did I hear that correctly?

Yannis Morel: Yes, Q4.

Sonia Quaratino: I appreciate your patience in this. As you know, it takes time to prepare for Type C meetings and also the FDA has their time. But I would say that in our next discussion, we may provide a bit more clarity.

Daina Graybosch: Very helpful. Thank you.

Operator: Your next question comes from the line of Yigal Nochomovitz from Citi. Your line is open.

Ashiq Mubarack: Actually, this is Ashiq Mubarack on for Yigal. Thanks for taking my questions. Just a couple on the early stage pipeline. So the CD20 ANKET asset that’s now in early development, I believe you said you have some time lines for data, I think you said next year. Can you give us a little color on what sort of signal you’re looking for to warrant further advancement there? And maybe what specific types of patients you’re enrolling? And then a similar question on the Nectin-4 development plan. Is the plan to enroll primarily post pads patients given the potential to treat MMA resistant patients? Any color there would be helpful. Thanks.

Herve Brailly: Sonia?

Sonia Quaratino: Right. On the IPH65, the CD20 ANKET, we are currently in dose escalation. During this year, we opened all the sites and we are progressing with dose escalation next year, what we intend to see is the completion of the dose escalation and moving to the dose optimization as project Optimus, which is let’s say, a mandatory step in the development of early-stage programs. And we are looking, of course, generating the safety or safety profile for this asset. Mind you that the first-generation ANKET developed by Sanofi have demonstrated a remarkably favorable safety profile, and we hope to confirm the same level of, let’s say, the same type of safety profile for — with the second generation ANKET, which include this extra IL-2 variant.

We, of course, are looking for pharmacodynamic markers. And therefore, we are looking to the level of B-cell depletion at different dose levels. We are looking at how much the ANKET sales are stimulated. And ultimately, we are looking at preliminary signs of antitumor activity. And so anything that has, let’s say, the classic preliminary activity that is demonstrated in Phase I trials. At the moment, we recruit Non-Hodgkin lymphoma. Mainly DLBCL, but we are open to many other, let’s say, sub-group of CD20 positive Non-Hodgkin lymphomas. And for the ADC in terms of clinical development plan, we are moving forward to the initiation of the Phase I by the end of the year. And our aim, again, this is going to be a first-in-human, a dose escalation, and we are recruiting indications that generally express, let’s say, a moderate level of Nectin-4 and these are let’s say, not only bladder or breast, but also non-small cell lung cancer.

Esophageal GJ tumor and so forth and the dose escalation will be done in this indication, and we, of course, expect to see preliminary signs of efficacy as alongside the safety profile and pharmacokinetic and pharmacodynamic markers. I hope I addressed your questions.

Ashiq Mubarack: And do you expect significant enrollment of patients pretreated with [Indiscernible] or…

Sonia Quaratino: We don’t know how many there may be, but definitely, this is not an exclusion criteria.

Ashiq Mubarack: Understood. Thank you.

Operator: [Operator Instructions] Your next question comes from the line of Swayampakula Ramakanth from HCW. Your line is open.

Swayampakula Ramakanth: Thank you. So I’m just trying to understand what’s the progress in the PTCL indication for lacutamab. If you can give us an idea of when you could expect some data from the Kill trial?

Herve Brailly: Sonia?

Sonia Quaratino: This is — yes. Thank you for the question. As you know, this is an IST that is, let’s say, sponsored by the Lisa Group. And we can say that the study is ongoing and recruiting. The study is not really under our direct control, but we can see that the study is on track for a termination late next year.

Swayampakula Ramakanth: Okay, thank you.

Operator: And we have a follow-up question from the line of Rajan Sharma from Goldman Sachs. Please go ahead.

Rajan Sharma: Hi, thanks for taking the follow-up. Just wanted to come back on one of my initial questions. And if I could just ask a question around CEO and strategy in a different way. Just wanted to be clear kind of to what extent can you make strategic decisions on things like lacutamab absent the CEO? Or will these things be on hold until you’ve made an appointment there? Thank you.

Herve Brailly: Yes. For sure, we prepare a scenario on the — we have a different options that we are contemplating for the next steps in the program and the decision will be made by the Board with the CEO in place.

Operator: We’re actually out of question. So will now conclude our question-and-answer session, and I would like to thank everyone for joining us today. This concludes today’s conference call. Thank you for your participation. You may now disconnect.