Innate Pharma S.A. (IPHA) Q4 2023 Earnings Report, Transcript and Summary

At this time, I would like to welcome everyone to the Innate Pharma Full Year 2023 Financial Results and Business Update Call. Today's conference is being recorded and all lines have been placed on mute to prevent any background noise. After the speakers' remarks, there will be a question-and-answer session. [Operator Instructions] And I will now turn the conference over to Henry Wheeler, Vice President of Investor Relations. Mr. Wheeler, you may begin.

Thank you. Good morning, good afternoon, and welcome, everyone. This morning, Innate issued a press release for our full year 2023 financial results and business update. We look forward to highlighting the progress made during the year-to-date as well as addressing future goals and milestones. The press release and today's presentation are both available on the IR section of our website. On Slide 2, 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 development. These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted. On Slide 3, on today's call, we will be joined by Herve Brailly, our Interim Chief Executive Officer. Then we will 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, Chief Operating Officer, who will then discuss ANKET and ADC platform updates. Frederic Lombard, our CFO, will cover the financials, and we're very pleased to welcome Arvind Sood, EVP, U.S. Operations, who will wrap up and close. Herve, I'll now hand the call over to you.

Thanks Henry. Good morning and good afternoon, everyone. I just like first to recall that Innate Pharma is a very important player on the field of, ADC pharmacology, on Innate immunity, manipulation. We address that through different mechanisms of actions where we have corresponding products. It's first about engaging NK cells, cytotoxic effectors to tumor cells and that's the approach that we implement with the ANKET platform, but also with the such toxic antibody lacutamab. We've also been pioneering the field of checkpoint inhibitors of NK Cells with monalizumab which is a checkpoint which is shared, which is targeting the checkpoint which is shared by different classes of effector cells both NK on T cells. And eventually through addressing suppression of the cytotoxic immune response through IPH62 and 63, which addresses the adenosine pathway. So that's it. What is the Innate Pharma strategy? Well firstly, it's about creating near-term value. That's what we want to achieve with our most advanced proprietary asset, lacutamab, for which is in development in T cell lymphoma on actually final CTCL on early PTCL data have been released by the end of 2023 at ASH. On here, we do look forward to the next step, which will be the data on mycosis fungoides and that will inform the future of this program for further late-stage development. Second, we continue to fuel our innovative portfolio with both ANKET on antibody drug conjugates. ANKET is really a core asset. It's a platform which generated several molecules. And as you know, the first molecule in clinic has been advanced by our partner Sanofi who published in '23 important first clinical data. We'll come back to that of course in greater details for the SAR443579. But the ANKET portfolio is now expanding with other assets that have been further licensed in by Sanofi, but also with the proprietary program that we recently announced is now and this is the second generation ANKET which has now been brought to clinic in Phase 1 in lymphoma. On beyond ANKET, we also advanced a second class of agents which are active as a single agent potentially in tumor with antibody drug conjugates. The first one being brought to, we work on bringing it to IND in '24. Eventually this is through partnership, we have monalizumab or checkpoint inhibitor in Phase 3 on AstraZeneca is pursuing this late-stage asset which will deliver in the next year very important data. So that translates into the portfolio which is a combination of proprietary product on the partnered asset. I will now leave it to Sonia to detail the clinical stages on the clinical progress with those effect on specialty on firstly with lacutamab. Sonia?

Thank you very much, Herve. When we look at Slide 7, I would like to summarize the progress we are making with lacutamab. And here on this phase, we are pursuing a fast to market strategy for lacutamab in the niche setting of Sezary syndrome, where lacutamab was granted the U.S. Fast Track Designation and EU PRIME Designation back in 2020. We and then expanded, post Sezary syndrome to mycosis fungoides where we have seen encouraging preliminary data from the Phase 2 TELLOMAK trial in patients that have a KIR3DL2 expression level above as well as below the threshold of 1%. And we expect to present this data to an upcoming conference later this year. Now the data in MF together with the data in excess will be shared with regulators to align on a path forward to maximize the value of lacutamab in CTCL building on the existing fast track and orphan designation. Now if we move to the PTCL space, today, we have announced that we are not going to reopen the recruitment of the Phase 1 testing lacutamab in monotherapy in PTCL. As the number of observed objective responses did not meet the pre-specified threshold for activity with lacutamab as a single agent. However, based on the data presented at ASH last year demonstrating the synergies between lacutamab and chemotherapy preclinical models of PTCL, we remain committed to the development on PTCL and continue to enroll patients in the Phase 2 combination trial with chemotherapy, gemcitabine and oxaliplatin, where we believe the combination can offer additional benefit to patient. On the next slide, Slide 8, we have a summary on the final Phase 2 data in Sezary that were presented at ASH last December in an oral presentation. This is a heavily pretreated post-mogalizumab patient pool with at least 5 million prior systemic line of therapies, including moga. And the global overall response rate was an encouraging 37.5%. I would like to note the deepness of the partial responses as you can see on the waterfall plot on the slide. We have also reported in this patient population an overall response rate of 46.4% in the skin and 48.2% in the blood. And overall a clinical benefit rate of 87.5% and a median PFS of 8 months with a durability of results of 12.3 months. A favorable safety profile was also observed, and we look forward to sharing this data set along with the final data in the causes from world's code with the regulator, later on. Now on Slide 9, we can switch gear to our most advanced proprietary ANKET, which includes a detuned variant IL-2 to include activation and proliferation of intact cells in the tumor microenvironment. We were pleased to announce earlier this month that IPH65, the first of the second-generation aggregates, which target CD20 has entered the clinic, and the first in human has started with the first patient being dosed in March. The trial will enroll patients with relapsed refractory and non-Hodgkin's lymphoma and we will run-in the U.S., Australia, and France. In B cell non-Hodgkin's lymphoma compared to recent therapies including CAR T and T cell engagers, at aged 65 as a disruptive mechanism of action that eliminates cancer cell via profound activation and proliferation of the NK cells. And IPH65 differs from allogeneic NK therapies including CAR-NK as it is an off the shelf therapy that drives the proliferation of the patient's own NK cells in non-Hodgkin's lymphoma and does not require any immune for the deletion as for other cell therapies. Now, the IPH65 pro forma also addresses the commentary and associated with the loss of CD16 by ensuring activation of intratumoral NK cells via the activation of NKp46. Finally, by stimulating the NK cell natural function, IPH65 has bystander effect that can cause the elimination of CD20 negative tumor cells overcoming tumor heterogeneity or loss of tumor antigen. Now I will turn to Yannis.

Thank you, Sonia. On Slide 10, I wanted to highlight our proprietary first in class NK cell engager platform that we call ANKET. ANKET is a versatile technology made of antibody derived building blocks that is creating an entirely new class of multi-specific engagers to induce synthetic immunity against cancer. Leveraging our scientific expertise in the antisense space, this platform is an enzyme for producing series of drug candidates addressing multiple tumor targets, both in heme and solid tumors. The activating NK cell effector for NKp46 is the backbone of our technology. And since it has a stable expression at the NK cell surface, even in the genomic environment, introduces an optimal activation of the NK effector functions. We have also developed a second generation version of the technology by incorporating a variant of INTERLINK-2 in order to induce NK cell proliferation. As you can see, our pipeline of ANKET molecule is significantly growing with Sanofi having now licensed 4 molecules. Two are in the clinic ANKET and two are at technical stage in solid tumor, including IPH67, which is a program for which Sanofi opted in December last year. We are also very pleased to see our proprietary portfolio of ANKET progressing. The second generation ANKET IPH6501 is now in the clinic and we continue to fuel our pipeline with new preclinical program against multiple targets. On Slide 11, you can see another view of the clinical data presented by Sanofi last year at ASH for the ANKET IPH6101 also named SAR’579. In this dose escalation, we were encouraged to see initial preliminary single agent activity and safety of SAR’579 in relapsed recurrent AML patients. At the 1mg/kg dose, 5 complete responses were observed out of 15 patients with 3 responder remaining in remission at beta cutoff at over 7, 12 and 14 months of treatment. Top SAR'579 was well tolerated up to 6 mg/kg with no dose-limiting toxicity observed and only 2 grade 1 CRS observed out of 43 patients. The FDA awarded SAR'579 Fast Track Designation in May, and we look forward to seeing further updates on Sanofi in due course. On Slide 12, you can see a summary of our Sanofi alliance. In 2016, we signed an initial agreement for 2 ANKET molecules worth up to EUR400 million in milestone plus roylaties among which we announced EUR60 million to date. Both program, SAR'579 and SAR‘514 are progressing to Phase 1 clinical trials. In December '22, we signed a second agreement whereby Sanofi licensed the IPH62 ANKET program targeting B7H3, a solid tumor target, and again optioned for two other targets. In December last year, they opted in for one of this program called IPH67 targeting an undisclosed tumor target in solid tumors, triggering a EUR15 million milestone and making EUR40 million the total of payment received from the second agreement. Altogether, considering these two agreements, we are eligible for a total milestone package of up to EUR1.75 billion plus royalties. Slide 13 highlights our growing antibody drug conjugate pipeline. As we continue to develop next generation therapeutics having single agent activity utilizing our antibody-engineering platform, we find that for some tumor targets we can generate antibodies with good internalizing property that therefore are well suited for ADC development. Our agreement with Takeda in the field provides the validation to this research approach and highlights our capability to generate differentiated ADC candidates. I will now cover updates on our lead proprietary ADC program, IPH45, on the next slide. Slide 14 highlights IPH45, which is our proprietary electing for targeted ADC with a Topo I inhibitor payload. We managed to create a differentiated product through multiple components. First, we generate a proprietary antibody with a differentiated epitope non-overlapping with enfortumab, the antibody backbone of PADCEV. Then we selected the validated clickable linker designed to be hydrophilic in order to counterbalance the hydrophobicity of the payload and to allow for a high blood antibody ratio. Finally, we selected a well validated Topo I inhibitor with bystander effect, allowing to bypass MMAE related resistance mechanism and to address tumors with pathogenicity making for expression. Altogether, these elements result in a differentiated making for ADC showing strong efficacy in preclinical models, including in fact set by factory PDX as well as encouraging PK tox profile in the non-human primates. These clinical data have been selected for presentation at the lower session at ACR in the coming couple of weeks. We are looking forward to presenting them and to filing the IND for this product this year. On Slide 15, I would like to remind you of monalizumab, the anti-NKG2A checkpoint inhibitor that we have licensed to AstraZeneca for oncology. In this slide, you can see another view of the late stage development plan for monalizumab in lung cancer. Mona is currently being investigated in a Phase 3 trial called PACIFIC-9. AstraZeneca started this Phase 3 evaluating the combinations of either mona or oleclumab plus durvalumab in the unresectable Stage 3 non-small cell lung cancer setting, who have not progressed after concurrent chemo-radiotherapy. Based on the results of their Phase 2 COAST trial. COAST data were published in the Journal of Clinical Oncology in '22 and after a median follow-up of 11.5 months, PFS data showed a hazard ratio of 0.42 in favor of mona with lacutamab combination versus durvalumab alone. The results also showed an increase in the primary endpoints of confirmed overall response for monalizumab and durvalumab combination or durvalumab alone of 76% versus 18%, respectively. The AstraZeneca sponsored NeoCOAST-2 study is also underway in an earlier setting of lung cancer, evaluating monalizumab and durvalumab with chemo in the neoadjuvant non-small cell lung cancer patients. Based on Phase 2 data from the NeoCOAST study, which showed also superiority of the monalizumab plus durvalumab combination or durvalumab in this neoadjuvant setting. I will now turn to Frederic for the financials.

Thank you, Yannis. On Slide 16, the key elements of the Innate's financial position and financial results as of the year ended 31st of December '23 is as follows. Cash, cash equivalents, short-term investment and financial assets amount to EUR102.3 million as of the end of last year, including financial instruments amounting to EUR9.8 million. This number does not include the EUR15 million payment received from Sanofi in January '24. Revenue and other income from continuing operations amounted to EUR61.6 million in '23, which mainly comprises revenue from collaboration and licensing agreements received pursuant to the agreements with AstraZeneca, Sanofi and Takeda, and EUR9.7 million in research tax credit. Operating expenses from continuing operations amounted to EUR74.3 million in '23 with R&D now making up 75% of the OpEx. Research and development expenses from continuing activities amounted to EUR56 million in '23, up 8.4% from prior year. The increase in R&D mainly results from an increase in direct research and development expenses, both clinical and nonclinical. General and administrative expenses amounted to EUR18.3 million, down by 18.5% on prior year due to the decrease in personnel expenses, non-scientific advisory fees and other expenses, mainly resulting from efficiency measures applied by the company. The table in the press release summarized the IFRS consolidated financial adjustments as of and for the year ended 31st of December 23, including 2022 comparative information. I will now hand over to Herve.

Thank you Frederic. I won't go through all the catalysts that we have listed on Slide 17, but I'll spend a few minutes on some of the key clinical catalysts that we have noted on this slide. And then we'll provide a summary before we turn to your questions. We are expecting the final data for a proprietary antibody lacutamab in mycosis fungoides imminently, and we look forward to presenting this data in detail at an upcoming medical meeting. Concurrent with that, we'll also commence interactions with the global regulatory agencies as we map out the next steps in its development. Our antibody therapeutic NK cell engager program that was earlier referred to as the ANKET program, this continues to evolve. This program has received broad validation through the licensing of 4 programs to Sanofi. We have recently taken a proprietary program emanating from this ANKET platform into the clinic ourselves by dosing the very first patient. This program known as IPH6501 is targeting CD20 in B-cell non-Hodgkin's lymphoma. For monalizumab, our antibody targeting NKG2A, the Phase 3 trial called PACIFIC-9 is underway. This is a study looking at monalizumab plus durvalumab in non-small cell lung cancer. The thinking here is that the dual targeting of the PD-L1 and the NKG2A pathways through this combination will lead to enhanced antitumor activity versus single-agent therapy. We continue to advance other agents targeting the adenosine pathway in the clinic, an example is IPH5201, which is currently in Phase 2 in combination with durvalumab and chemotherapy in treatment-naive patients with resectable early-stage non-small cell lung cancer. So just to conclude, over the years, we have established a strong expertise in immunopharmacology with definitive Phase 2 data in hand, we are mapping out the regulatory next steps for lacutamab. Our proprietary NK-cell engager platform ANKET has the potential of addressing both hematologic malignancies and solid tumors. We are pursuing ADCs with a focus on differentiation with IPH45. This is our ADC targeting Nectin-4, being a key example of our approach. And lastly, we continue to retain a strong cash position to fund our operations well through the end of 2025. We are excited about our prospects for the future. And before I close, I would also like to thank the many employees at Innate, who work very hard in developing therapies for the potential benefit of patients. With that, we can open it up for questions.

[Operator Instructions] We will take our first question from Yigal Nochomovitz with Citi.

This is [indiscernible] on for Yigal. We had a couple. First on the PTCL program which you are not planning to reopen the Phase I monotherapy trial. Can you walk us through your thought process there and give us more details on that? And what was the internal bar for efficacy there? And then on the second -- again, unlike lacutamab where your spending within the process of finding a partner for the commercialization and development of the program? Are you expecting the upcoming data for MF to capitalize the partnership there?

Right. Let me say that we have -- in PTCL, we have enrolled 20 patients and the data around safety from 10 patients were presented at ASH last year. But probable, we have included a formal, let's say, interim analysis where we define a minimum number of objective responses that needed to be observed prior to continuing the recruitment. And despite we observed some objective responses in PTCL, we like to have in monotherapy. This number of objective responses did not meet the minimum number recent by the protocol. As you understand, in PTCL, there are many different therapeutic options and many already provide quite a robust number of objective responses and there for our -- our threshold though was quite high, too much. We remain, however, committed to the PTCL through the Phase 2 study in combination with chemotherapy, where we expect to see some synergism between lacutamab and chemotherapy and therefore, provide some meaningful clinical benefit to patients. The second question was around the partners. Is that correct?

The second question was on partnership, yes.

Partnership. And around the partnership for lacutamab, we are actively looking for different options to pursue the next stage with lacutamab in the CTCL either via partnership or alternative options.

And just one quick follow-up. Do you expect discontinuation of monotherapy impact your plans on the partnership for this molecule?

Not really. I mean the data on PTCL have no impact neither on the Phase 2 in PTCL in combination with chemo, but definitely not on the CTCL where we already have the data in-house.

We will take our next question from Daina Graybosch with Leerink Partners.

I'm going to ask a follow-up on the one just asked on the single agent activity. It's hard because we can't see it. And so is this you had one response and you had a lot of shrinking stable disease? Or did you have 3, and I just didn't meet your bar. And so I wonder if you could give us any more specific details, particularly because I think we'd like to -- what should make us confident clinically that this is going to prove out in [indiscernible] to be something more meaningful for patients and the unmet need compared to the therapeutic options here.

This is the operator. I apologize did our presenters go on mute? Ladies and gentlemen, we are experiencing technical difficulties. Ladies and gentleman, I will put music back on for our speakers to reconnect. Thank you. Hello, Henry. This is Abby. All right. And let me make a slide once again. Ladies and gentlemen, thank you for your patience, while we managed our technical difficulties. Ms. Graybosch, do you mind asking your question again, please?

That came from CD, which is I wonder if you could give us any more details on the specific responses or any correlation with KIR3DL2 activity? What in the clinical data could we hang on to be confident that we're going to see synergy in combination with chemotherapy next year?

I suspect you are talking about the PTCL rather than the mycosis fungoides.

Yes.

Basically, in this study, we have recruited the patients to have an expression level of KIR3DL2 that is equal or above 1%. We did not, let's say, restricted to any subtype of PTCL and we hope to present the data later on this year. Even if we are not going to reopen the study and the sample size is relatively small because it's around 20 patients.

So then what gives you confidence in the GEMOX combo will prove successful?

This is an investigator-sponsored trial, and date of completion is predicted to be towards the end of 2025.

And yes, but why do you think that this will be successful? Why continue with the IIIB.

Because at ASH last year, we have presented some data that demonstrate some synergism in preclinical model with lacutamab and chemotherapy.

Operator, I'll ask an off-line question and then maybe we can go back to the online questions. So I have an off-line question from Justine Telliez at Kepler Cheuvreux. On lacutamab, regarding the potential progress made with the regulatory authorities in Sezary syndrome, can you give us an update? And also at what point are you regarding [indiscernible] partner, which I think you covered already. So regulatory interactions.

Well, we are working. Now that we have the data in MF and these data are -- and this data are this preliminary -- this data are promising. We are -- we are working to -- for a fast forward alongside SS and MS and a plan to maximize the value of lacutamab that is going to be discussed with the regulators.

Our next phone question comes from Arthur He with H.C. Wainwright.

This is Arthur in for RK. So I just want to follow-up on the regulatory question on lacutamab. So are you guys to go to the agent with the data, both with Sézary syndrome and the MF rather go for the Sézary syndrome data alone to talk to the agent to file the BLA. Just want to clarify that.

Sure. Originally, we -- when we had the data of Sézary, there was the option of going to the regulators with Sézary data alone, where we had a Fast Track Designation and PRIME. Now we can really plan to merge the data, as I said, to maximize the value of lacutamab not only in Sézary that is a small sub group of the CTCL, but maximize the value of the drug in the whole of CTCL together, of course, with mycosis fungoides. And of course, the other option of asking for accelerated approval still remains. And as you know, in order to get accelerated approval anyway, we need 12 months durability of response that is needed for this. And of course, we need to align on what the registrational trial could look like.

Just quick on the ANKET program. It's great to see the progress along and the expanding of the portfolio. Specifically on the 6501, I'm just curious for the trial, you're going to evaluate initially. Would -- is there CD20 color for the patient inclusion? And how about the dosing strategy there, if you can give additional color. Appreciate it.

Sure. In the study are going to be recruited, the CD20 positive non-Hodgkin lymphoma. Again, in every subtype. And this is a classic first human trial. And therefore, we are the first cohort, as you can imagine, as the first patient was enrolled in March. It's a dose escalation study with expansion.

And how about the dosing wise? What's the dosing interval and the strategy for the dosing escalation?

Well, the dose escalation is guided by the safety signals that we see and, of course, by statistical consideration and appetite of the investigators depending on the safety and the exposure that we observed at each cohort.

We have no further phone questions at this time. I would now like to turn the call back to Mr. Herve Brailly for any closing remarks.

Yes. Thanks a lot for your questions. And we're looking forward to the next meeting and the next important steps will be the presentation. The overall presentation at the ACR to present the features of ADC, OCD, the IPH45 and then, of course, the general meeting taking place on May 21. So we're looking forward to reconnecting with you all on those two opportunities. And I wish you a very good day, and looking forward to the next steps.

Ladies and gentlemen, this concludes today's call, and we thank you for your participation. You may now disconnect.