Innate Pharma SA

PAR:IPH

Earnings Call Transcript 2021-Q3

[Operator]

Good afternoon, ladies and gentlemen, and welcome to Innate Pharma's Third Quarter 2021 Business Update Conference Call. [Operator Instructions] As a reminder, this conference call is being recorded. [Operator Instructions] I will now hand over to Innate Pharma's Chairman of the Executive Board and Chief Executive Officer, Mondher Mahjoubi. Please go ahead, sir.

[Mondher Mahjoubi, Chairman of Executive Board & CEO]

Thank you. Good morning, good afternoon, and welcome, everyone. This morning, we issued a press release providing a business update for the third quarter of 2021. I look forward to explaining the progress we made during the year to date as well as address some future goals and milestones. The press release and today's presentation are both available on the IR section of our website. Please move to Slide #2. And before we start, I would like to remind you that we will make 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. You have on today's call, I'm delighted to be joined for the presentation by Mr. Joyson Karakunnel, EVP and Chief Medical Officer; we will have our CFO, Frederic Lombard; and Yannis Morel, Head of Business Development and Portfolio Strategy joining for the Q&A session. Please move to Slide #4. Our pipeline shows how we have translated this into a robust portfolio of proprietary and partnered assets. It also illustrates how we are executing against our strategy with our lead proprietary asset, lacutamab but also supported by [indiscernible] and earlier stage products. We are pleased to see the progress of monalizumab in early lung cancer and await more data in head and neck cancer later this year. The added impact [ for it ] continues to progress with 2 antibodies in the clinic, the anti-CD73 IPH5301, and IPH5201 which targets CD39 and is in partnership with AstraZeneca. In addition, we have a pool of projects including our ANKET, NK cell engager platform, which we are excited to see nearing the clinic with our partner, Sanofi. Slide 4, please -- Slide 5. Let me remind you our strategy. As you know, our strategy centers around 3 core priorities, where we look to drive value from early R&D efforts through later stage partnership where it makes sense to us. Firstly, we look to take near-term value, driven by our lead proprietary product candidate, lacutamab, which is in development for T-cell lymphoma. As you may remember, we presented exciting data earlier this year at the Lugano meeting in mycosis fungoides and we look forward to further readout next year along with the advancement of the background T-cell lymphoma program. Second, we sure [indiscernible] longer-term value by leveraging our antibody exiting capabilities to develop innovative molecules with a primary focus on our multi-specific NK cell engager proprietary platform called ANKET. [indiscernible] selected by Sanofi with an [indiscernible] tumor antigen will be investigated in acute myeliod leukemia in the clinic very soon. Third, we are building a strong and sustainably foundation for our business, leveraging various partnerships across industry and academia. We will look to partner, including a late stage when it makes sense to do so. This will further validate our science and offer capital that you can invest to advance our early portfolio. As we come to monalizumab, which Joyson will cover in a minute, I would like to remind you that in 2018, we out-licensed [indiscernible] oncology to AstraZeneca and that we have received in aggregate USD 400 million in milestones to date with further potential milestones dip. We were very pleased to see our partner, AstraZeneca announced plans to advance monalizumab into another registrational trial and continue to explore its potential in other settings. I would like now to pass the call over to Joyson, who will review the progress made with our portfolio, starting with monalizumab, our most advanced asset. Joyson?

[Joyson Joseph Karakunnel, Executive VP & Chief Medical Officer]

Thank you. Thanks, Mondher. To remind you, monalizumab is an anti-NKG2A, which acts upon the checkpoint pathway to potentiate NK cell activation. This is being trialed in combination with cetuximab in head and neck cancer and also in combination with the anti-PD-L1 durvalumab in lung cancer. On this slide, I wanted to recap the results for the randomized Phase II study that AstraZeneca conducted in unresectable Stage III non-small cell lung cancer presented at ESMO in September. The 3-arm study evaluated the combinations of durvalumab plus [indiscernible], AstraZeneca's anti-CD73. As you can see from the results here, both arms performed well versus the standard of care earned durvalumab. After a median follow-up of 11.5 months, the results of an interim analysis showed a 10-month PFS rate of 72.7% for durvalumab plus monalizumab versus 39.2% with durvalumab alone. The results also showed an increase in the primary endpoint of confirmed ORR for durvalumab plus monalizumab over durvalumab alone of 36% versus 18%. The discussion at ESMO also highlighted a matched propensity score analysis which matched certain variables, which are known prognostic indicators. This demonstrated that the COAST study may have recruited patients with the worse prognosis explaining the durvalumab arm underperforming versus the Phase III PACIFIC trial. On Slide #7, you can see an overview of the late-stage development plan for monalizumab in lung cancer. As mentioned, based on the Phase II COAST data, AstraZeneca announced plan to initiate a Phase III trial for both combinations of monalizumab and oleclumab plus durvalumab in the unresectable Stage III non-small cell lung cancer setting, who had not progressed after concurrent chemoradiation. We look forward to seeing the trial announcement in due course. Separately, AstraZeneca also announced that it is starting a Phase II clinical trial in the earlier Stages IIa to IIIa non-small cell lung cancer, NeoCOAST-2 that includes a treatment arm with monalizumab in combination with durvalumab and chemotherapy. We still await the data from the Phase II NeoCOAST trial and Stage I to IIIa non-small cell lung cancer patients. On Slide #8. Moving to head and neck cancer, we presented data from cohort 3 of the Phase II trial later this year at ESMO-IO for the triplet of monalizumab plus durvalumab plus cetuximab in the first-line head and neck cancer. As a reminder, the standard of care in this setting is KEYNOTE-048 trial of pembrolizumab with or without chemotherapy depending on the PD-L1 status as determined by CPS score. Additionally, the Phase III INTERLINK-I trial of monalizumab plus cetuximab in IO pretreated head and neck cancer is ongoing. We look to work further with our partners, AstraZeneca on this potential new treatment. Turning to Slide 9. We are pleased to have presented our latest innovation in our proprietary multi-specific NK cell engager platform that we call ANKET, which Eric Vivier has presented at several meetings this year, including ESMO and SITC this last week. ANKET stands for Antibody-based NK cell Engager Therapeutics. And these multi-specific molecules are made of various building blocks as illustrated here. The reason why we are so excited about the ANKET is because we are announcing 2 breakthroughs. First, a technological breakthrough and second, an efficacy breakthrough, which is leading to the harnessing of NK cell effector function against cancer and also provides proliferation. So on the technological breakthrough, as you can see on this slide, ANKET is a versatile fit-for-purpose technology that is creating an entirely new class of tri- and tetra-specific molecules to induce strategic immunity against cancer. On the preclinical efficacy breakthrough, this unique NK cell engager engages for the first time to activating NK cell receptors, namely NKp46 and CD16, but also the combination of receptors for IL-2, IL-2R beta and IL-2R gamma with the IL-2 variant and tumor antigen in a single tetra-specific molecule. Overall, it demonstrates that better antitumor efficacy than clinically approved antibodies within the limit of preclinical models. On Slide 10 is a summary of the data presented at SITC this weekend on our lead ANKET asset as selected by Sanofi. This is the first NKp46/CD16-based NK cell engager to enter the clinic. On the left side of this slide, we demonstrated preclinical data showing that CD123 targeted IPH6101 ANKET demonstrated consistent potent antitumor activity against all AML cell lines and primary AML, which were resistant to ADCC by a competitor, anti-CD123 antibody. On the right side of the slide, we demonstrate that in nonhuman primate, there is a sustained pharmacodynamic effect combining efficient depletion of CD123-expressing cells with minor cytokine release and a favorable safety profile in comparison to T-cell engagers. We await the first clinical trial start with Sanofi. On Slide 11, we wanted to highlight the data on our recent generation of tetra-specific ANKET, which is made of 4 components. In yellow, an antibody fragment that recognizes the tumor antigen; in green, an antibody fragment that recognizes NKp46, and an Fc portion that will interact with the CD16; and then in blue, a variant of the interleukin 2. On the left, we show you the contribution of the tetra-specific ANKET with the IL-2 variant. The black graph on the far left is the vector. The green graph is the tetra-specific ANKET. And the red graph on the right is the ANKET and the IL-2 separated. You can sit with the green grass which is including the tetra-specific ANKET with the IL-2 variant. On the right, we see the benefit of the tetra-specific versus the vehicle obinutuzumab in lung mouse models. On top, you have the vehicle. In the middle, the tetra-specific ANKET and on the bottom, the CD20, obinutuzumab. Activity is seen with the tetra-specific model that is not seen in obinutuzumab. We look to further updates on the ANKET throughout the year -- throughout next year. On Slide 12, let me summarize the progress we are making with lacutamab, our first-in-class humanized monoclonal antibody that targets the immune receptor KIR3DL2. As you may remember, KIR3DL2 is an inhibitory receptor found in approximately 65% of patients across all cutaneous T-cell lymphoma and even more in certain aggressive subtypes, but with limited expression in healthy tissue. To date, lacutamab have shown promise, demonstrating compelling single-agent activity and offering immense potential in lymphomas historically associated with the core prognosis for which there are a few therapeutic options at an advanced stage. We are pursuing a fast-to-market strategy for lacutamab in T-cell lymphomas with a potentially pivotal trial underway in the niche indication of Sézary syndrome where lacutamab was granted U.S. Fast Track designation and EU designation last year. We are also looking to potentially expand past Sézary syndrome to mycosis fungoides, where we have seen encouraging preliminary data from our Phase II trial. For the Sézary syndrome, cohort enrollment is on track, and we still expect to be able to report top line preliminary data in 2022. In mycosis fungoides, firstly, we moved the KIR3DL2 expressing cohort from Stage I to Stage II earlier than anticipated. The data presented at Dana demonstrated a 35% ORR in KIR3DL2 expressing late-line patients. The next preliminary MF data update is due in 2022. Finally, we are advancing into peripheral T-cell lymphoma by starting 2 clinical trials in the relapse setting. With that, I'll turn back to Mondher.

[Mondher Mahjoubi, Chairman of Executive Board & CEO]

Thank you, Joyson. Before we conclude, let me remind you our key newsflow for the remainder of the year and for next year on Slide 13. As you can see, we are working diligently to execute across all our strategic pillars, and we believe that we are laying the foundation to drive near and long-term value for patients and shareholders. Looking at our clinical program, we expect to achieve a number of milestones over next year. As you've heard from Joyson, our Phase II TELLOMAK study for lacutamab continues to progress. We continue to expect to report preliminary data from the potential [ internal ] trial in Sézary syndrome as well as data in mycosis fungoides next year. We are also moving our PTCL program into the clinic with initial data expected next year. For monalizumab, we look forward to further clinical development in head and neck cancer, both unresectable and locally advanced -- new advance as well as the updates from the Phases III study in head and neck cancer by the end of this year. We continue to advance the adenosine pathway agents in the clinic, where we are starting a Phase I trial for IPH5301 the anti-CD73, and we look forward to data from the anti-CD39 IPH5201 in 2022. In parallel, we continue to develop our ANKET technology platform and we are very encouraged by the clinical results from our next-generation NK cell engager. We look forward to our lead ANKET entering the [ clinic ] soon with Sanofi and also for updates for ANKET throughout 2022. Let's move to the conclusion slide, please. As you can tell, we continue our exciting journey at Innate. We look to build our business to create value for patients and stakeholders. And in summary, we have positioned Innate Pharma for the future with our strategy, and we have made meaningful progress throughout the year. Just to recap, in summary, lacutamab, we move forward with our TELLOMAK trial with encouraging mycosis fungoides data and are advancing into peripheral T-cell lymphoma with 2 clinical trials and [indiscernible] setting. Second, our R&D engine was further validated as Sanofi advanced IPH6101 into the clinic, and we look to further develop our proprietary ANKET NK cell engager molecules. Third, we look forward to seeing AstraZeneca as [indiscernible] plan for more original registrational study in unresectable Stage III non-small cell lung cancer. Finally, we maintained a strong cash position with EUR 141.8 million as of September 30. As a reminder, costs and expenses jumped around a bit on a quarterly basis as revenue and milestone vary from quarter-to-quarter. That concludes our prepared remarks, and we will now open the call to questions. Thank you.

[Operator]

[Operator Instructions] Our first question comes from Yigal Nochomovitz from Citigroup.

[Yigal Dov Nochomovitz, Research Analyst]

I'm not sure how much you'll be able to say on this question, but could you elaborate on AstraZeneca's strategy with respect to the Phase III in unresectable Stage III non-small cell lung cancer, meaning assuming the Phase III trial works for both the combo of mona plus durva and [indiscernible] and durva, do you believe that both combinations are going to be taken forward to commercialization? Or will this be more like a bake-off situation where AstraZeneca will select the combination with the best data versus durva monotherapy?

[Mondher Mahjoubi, Chairman of Executive Board & CEO]

Thank you, Yigal. Again, I think Joyson is the right person to address this question [indiscernible] match on the plans and the idea, and I would stick to what they have announced at the ESMO congress office, they are planning to move on with the [ registration ], but Joyson, in your view, any more color to provide on the Phase III program that has had in case currently?

[Joyson Joseph Karakunnel, Executive VP & Chief Medical Officer]

No. I mean, as the study is being sponsored by AstraZeneca, we also don't have any further information than what is publicly available.

[Yigal Dov Nochomovitz, Research Analyst]

Okay. And then are you able to answer this, when should we expect the final results from the COAST trial? And do you think we're going to have those results before the Phase III starts?

[Mondher Mahjoubi, Chairman of Executive Board & CEO]

Again, I would speak to what AstraZeneca announced in September that they are moving ahead with the Phase III planning for Stage III [indiscernible] they will present final results in due time. They did not communicate on the precise timing of that.

[Operator]

Our next question comes from Daina Graybosch from SVB Leerink.

[Daina Michelle Graybosch, MD of Immuno]

Two for me. The first is, I know you've communicated in the past, but I wonder if there's any update for our expectations for ESMO-IO for this triplet. And in terms of number of patients, whether should we reach the expectations to be on low and high, CD16 positive, negative? That would be helpful.

[Mondher Mahjoubi, Chairman of Executive Board & CEO]

So Joyson, I know that [indiscernible] data for the question. The meeting is a few days away, and I'm not sure that Joyson can provide more details other than what is on the public website. Thanks, Joyson.

[Joyson Joseph Karakunnel, Executive VP & Chief Medical Officer]

Correct. As Mondher said, we will be presenting the preliminary data for cohort 3 at ESMO-IO. As the meeting is only a few days away, there is no further information to provide [indiscernible].

[Daina Michelle Graybosch, MD of Immuno]

Okay. The second question is -- sorry, another one on AstraZeneca. So AstraZeneca has been developing the CD39 that they licensed from Innate Pharma in a rather big trial on clinicaltrials.gov, they recently modified that trial to stop recruiting after about 60 patients. And I wonder if you could give us any context on that decision or that change from AstraZeneca?

[Mondher Mahjoubi, Chairman of Executive Board & CEO]

Actually, thank you, Daina, for again, giving us the opportunity to address the partnership around 5201, it is assumed that the trial on [indiscernible] is, I'd say, appears as [ stop ] the position of AstraZeneca, the data, the Phase I trial in solid tumors or sick tissues alone, on combination with durvalumab are expected to be presented next year. Following the review of the full -- of the data in full review we'll be detailing in the outlook is as for this medicine within their portfolio.

[Operator]

Our next question today comes from Keyur Parekh from Goldman Sachs.

[Keyur Parekh, Equity Analyst]

Two please, if I may. The first one on lacutamab. Just wondering, Mondher, if you can talk to us about the probability of the data you see in 2022 being acceptable from a filing purposes. So could this molecule potentially be on the market in 2023? That's kind of question number one. And then separately, you guys have a lot of kind of interesting Phase I, Phase II studies that you're currently starting kind of next year. So would be keen to understand how you're thinking about kind of ballpark R&D costs kind of into next year?

[Mondher Mahjoubi, Chairman of Executive Board & CEO]

Yes. Thanks to you. A very, very important question. I'll start with the second one, and then I'll hand over to lacutamab. I think it's probably important to also remind you that our strategy is really to develop proof, of course, everybody at the same time. But now, whenever it makes sense to do so even at a later stage. And fact of the matter is that we have development program with AstraZeneca around monalizumab, but we have room within our finance to deliver our own clinical development program and our own Phase I, II program, both for lacutamab but also for our entire CD73. I think we have a very strong cash position to cover the various milestones that we have and to execute on our strategy. We are not worried about the ability to execute those initial trials with the limitation that, you know, in this field, a lot of competition and we are also only competing for the same patient, but sometimes it's challenging within the COVID environment. However, I think it's now more easier for anti-CD73 to be developed and given the proof of concept that AstraZeneca has made in the COAST trial. And similarly for the clinical T-cell lymphoma. I think the data we presented at the Lugano meeting, were another proof point that this drug works beyond Sézary syndrome, and of course, makes a strong case for further development impact on T-cell lymphoma. And as you know, we are doing this development in two ways: a company-sponsored trial, testing the ages in monotherapy in a sort of Phase Ib trial in second [indiscernible] PTCL, essentially in the U.S. And we have a second trial that is mainly in Europe that is sponsored by the [indiscernible], and it's [ optimized ] to try that in the combination with [indiscernible]. I hope it addresses your question about that and the ability to [indiscernible] on. Joyson, can you provide a refresh on our registration strategy and fast-to-market strategy for lacutamab and the data we are acquired in [indiscernible].

[Joyson Joseph Karakunnel, Executive VP & Chief Medical Officer]

Yes, definitely. So in regards to question number one, as was mentioned during the [ slide ] and as Mondher mentioned, we do have a first-to-market strategy with SS as well as mycosis fungoides with close follow-on indication. We are expecting -- we are anticipating preliminary data in 2022 and recruitment is on track right now. Our final data is expected in 2023. The potential for the SS, or the Sézary syndrome to be -- it can be pivotal. So the cohort in Sézary syndrome can be a pivotal cohort. And just keeping in mind, we do have Fast Track designation in the U.S. and Prime designation in the E.U., for potential -- for our proactive support from the regulatory authorities and for accelerated assessments. At least right now, it's early to speculate on potential launch time line. And we'll make a sort of data-driven decisions and follow through with these discussions as we continue to speak with the regulatory opposites.

[Operator]

[Operator Instructions] Our next question comes from Olga Smolentseva from Bryan Garnier & Co.

[Olga Smolentseva, Research Analyst]

I had a Q on 6101 -- basically multiple therapeutic modalities that targets CD123 did merge adequate risk-benefit ratio. Starting from anti-CD123 antibodies to bispecifics and [ ADCs. ] So for you, what maybe are the key differentiating factors for NK cell engagers to sort of balance risk-benefit ratio in this context?

[Mondher Mahjoubi, Chairman of Executive Board & CEO]

Thank you, Olga. I'm going to hand over the question to Yannis Morel, who is Lead in the Portfolio Strategy and provide more color on the IPH6101 development. Yannis?

[Yannis Morel]

Yes, I think that the proof key feature of our molecule and our approach that we actually presented at SITC this weekend in the [ poster ] in collaboration with Sanofi is that our molecule is able to induce a very important killing on the AML [ blasts ] from patients and irrespective of the subset of the patients. And we found out that some [ blasts ] are resistant to killing by a traditional antibody-inducing -- ADCC-inducing antibody because of the expression of some [indiscernible] receptor on the [indiscernible].So that's the first one, meaning that we can potentially have efficacy in a broader subset of population of patients in [indiscernible]. And the other key differentiating factor that you can see in the data that we have obtained both in nonhuman primate, but also in, in vitro using human cells and comparing our NK cell engagers with T-cell engager is that we are able to induce killing of cells but without inducing systemic cytokine release. We are inducing very low cytokine that we can potentially -- those pretty high here, the molecule results in using the systemic side effects of the unwanted cytokine release which is a -- which is, by the way, one of the limitations of the T-cell engager. You may have noted that, for example, [indiscernible] the agreement with [indiscernible] is not pursuing the T-cell engager in the same target mainly for this kind of reason of the [ holding.]

[Olga Smolentseva, Research Analyst]

And maybe considering recent data from competitor in AML sort of pointing towards a need for improved proliferation signaling. I'm just curious if tetra-specific ANKET in this business setting would sort of be a better choice?

[Mondher Mahjoubi, Chairman of Executive Board & CEO]

I think it's probably too early to start to base about the positioning of such antibody, but it's clear that the medical need in this field is still extremely high. And we are looking forward to initiating the Phase I, defining the safety profile of the drug and looking at the efficacy signal in this early stage before giving more perspective on the role that this drug can play. From clinical data and the package that we developed with our partner is quite convincing and of course, convinced the Sanofi to select our formats and to move it into the clinic. So I think we need to be very cautious and wait for the clinical data to emerge first before having a much more clear idea on the potential of this drug in the management of AML patient. Of course, a singulated but more important, as you can get in combination with other key standard treatment in AML in the various subtypes of new disease.

[Olga Smolentseva, Research Analyst]

Congratulations on the progress.

[Mondher Mahjoubi, Chairman of Executive Board & CEO]

Thank you. Operator, any more questions?

[Operator]

We currently have no further questions. So I'll hand back to Mondher Mahjoubi for closing remarks.

[Mondher Mahjoubi, Chairman of Executive Board & CEO]

Thank you, Emma. So as you can tell, collectively, we are really driving value across our business. And sequentially, I think we are advancing our goal to deliver innovative medicine integration. We look forward to keeping you updated on our progress, and thank you for your interest and listening to this call. Have a good day.

[Operator]

This now concludes today's call. Thank you for joining. You may now disconnect your lines.