Good afternoon, ladies and gentlemen, and welcome to Innate Pharma's third quarter 2021 business update and conference call. At this time, all participants are in listen-only mode. As a reminder, this conference call is being recorded. If you would like to ask a question at the end of the presentation, please press star followed by the number 1 on your telephone keypad. If you change your mind, please press star followed by the number 2. I will now hand over to Innate Pharma's Chairman of the Executive Board and Chief Executive Officer, Mondher Mahjoubi. Please go ahead, sir.
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 addressing 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 number 2. 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 number 3, on today's call, I'm delighted to be joined for the presentation by Dr. Joyson Karakunnel, EVP and Chief Medical Officer.
We have our CFO, Frédéric Lombard, and Yannis Morel, Head of Business Development & 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 partnering 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 adenosine pathway continues to progress with two antibodies in the clinic, the anti-CD73 oleclumab 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 it enter the clinic with our partner, Sanofi. Slide four, please. Slide five. Let me remind you of our strategy. As you know, our strategy centers around three core priorities, where we look to drive value from early R&D efforts through later-stage partnerships where it makes sense to do so. Firstly, we look to create 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 on mycosis fungoides, and we look forward to further readouts next year along with the advancement of the broader T-cell lymphoma program.
Second, we fuel our pipeline to create longer-term value by leveraging our antibody engineering capabilities to develop innovative molecules with a primary focus on our multi-specific NK cell engager proprietary platform called ANKET. The lead compound selected by Sanofi with an anti-CD123 tumor antigen will be investigated in acute myeloid leukemia in the clinic very soon. Third, we are building a strong and sustainable foundation for our business, leveraging various partnerships across industry and academia. We will look to partner, including in late stage, when it makes sense to do so. This will further validate our science and offer capital that we can then 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 the rights in oncology to AstraZeneca, and that we have received in aggregate $400 million in milestones to date, with further potential milestones due. We were very pleased to see our partner, AstraZeneca, announce plans to advance monalizumab into another registrational trial, and we 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?
Thank you. Thanks, Monde. 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 three-arm study evaluated the combinations of durvalumab plus mono, durvalumab plus oleclumab, AstraZeneca's anti-CD73. As you can see from the results here, both arms performed well versus the standard of care arm 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 worst prognosis, explaining the durvalumab arm underperformance versus the phase III PACIFIC trial. On slide number 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 in stage I to IIIA non-small cell lung cancer patients. On slide number 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.
The phase III INTERLINK-1 trial of monalizumab plus cetuximab in IO-pretreated head and neck cancer is ongoing. We look to work further with our partners from 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 two 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.
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 pre-clinical 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 a better antitumor efficacy than clinically approved antibodies within the limit of pre-clinical 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 primates, 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 four components. In yellow, an antibody fragment that recognizes the tumor antigen. In green, an antibody fragment that recognizes NKp46, and in an Fc portion that will interact with the CD16. Then in blue, a variant of the interleukin two.
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. The red graph on the right is the ANKET and the IL-2 separated. You can fit with the green graph, which is including the tetra-specific ANKET with the IL-2 variant. On the right, you see the benefit of a 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 with obinutuzumab. We look to further updates on the ANKET 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 lymphomas and even more in certain aggressive subtypes, but with limited expression in healthy tissue. To date, lacutamab has shown promise, demonstrating compelling single agent activity and offering immense potential in lymphomas historically associated with a poor prognosis for which there are few therapeutic options at an advanced stage. We are pursuing a faster 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 US 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 1 to stage 2 earlier than anticipated. The data presented at ASCO 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 two clinical trials in the relapsed setting. With that, I turn back to Mondher.
Thank you, Joyson. Before we conclude, let me remind you our key news flow 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. 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 potentially pivotal 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 early lung cancer, both unresectable and locally advanced neoadjuvant, as well as the updates from the phase II 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 IPH5201, 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 preclinical results from our next-generation anti-CD123 engager. We look forward to our lead ANKET entering the clinic soon with Sanofi and also for updates on our 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. 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. First up, we moved forward with our TELLOMAK trial with encouraging mycosis fungoides data and are advancing lacutamab with two clinical trials in the United States. Second, our R&D engine was further validated as Sanofi advanced SAR443579 into the clinic, and we look to further develop our proprietary ANKET NK cell engager molecules. Third, we look forward to seeing AstraZeneca's upcoming plan for monalizumab registrational study in unresectable stage III non-small cell lung cancer. Finally, we maintain a strong cash position with EUR 141.8 million as of September thirtieth.
As a reminder, costs and expenses jump around a bit on a quarterly basis as revenue and milestones vary from quarter to quarter. That concludes our prepared remarks, and we will now open the call to questions. Thank you.
If you would like to ask a question, please press star followed by number one on your telephone keypad. Our first question comes from Yigal Nochomovitz from Citigroup. Please go ahead, Gal. Your line is now open.
Hi, Mondher and Joyson and team. Well, 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 and unresectable stage III non-small cell lung cancer? Meaning, assuming the phase III trial works for both the combo of Mona plus durva and oleclumab and durvalumab, 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 durvalumab monotherapy?
Thank you, Yigal. Again, I think Joyson is the right person to address this question. AstraZeneca didn't match on their plans, and I would stick to what they have announced at the ESMO conference, that they are planning to move on with the registration file. Joyson, in your view, any more color to provide on the phase III program that AstraZeneca is planning?
No. I mean, as the study is being sponsored by AstraZeneca, we also don't have any further information than what is publicly available.
Okay. 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?
Again, I would stick to what AstraZeneca announced in September that they are moving ahead with the phase III planning for stage III unresectable cancer, and they will present final results in due time. They did not communicate on the precise timing of that.
Okay. Got it. Thank you.
You're welcome.
Thank you. Our next question comes from Daina Graybosch from Leerink Partners . Please go ahead. Your line is now open.
Hi, guys. Thank you for the question. Two for me. The first is, I know you've communicated it in the past, but I wonder if there's any update for our expectation for ESMO IO, for the triplets and in terms of number of patients, whether we should expect PD-L1 low and high, PD-1 positive negative. That would be helpful.
Joyson and I know that. Thank you, Dana, for the question. The meeting is a few days away, and I'm not so sure that Joyson can provide more details other than what is on the public website. Thanks, Joyson.
Correct. As Mondher said, we will be presenting the preliminary data for cohort three at ESMO IO. As the meeting is only a few days away, there's no further information to provide until the embargo is lifted.
Okay. The second question is, sorry, another one on AstraZeneca. 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. I wonder if you could give us any context on that decision or that change from AstraZeneca.
Actually, thanks, Daina, for giving us the opportunity to address the partnership around IPH5201. It is true that the trial a few years ago, let's say, appears to have stopped. The position of AstraZeneca is that the data, the phase I trial in solid tumors, IPH5201 alone or in combination with oleclumab are expected to be presented next year. Following the review of the full data, AstraZeneca will be determining the appropriate path forward for this medicine within their portfolio.
Okay. Thank you.
You're welcome.
Our next question today comes from Keyur Parekh from Goldman Sachs. Please go ahead. Your line is now open.
Hi. Thank you. Thank you for taking my questions, 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. Could this molecule potentially be on the market in 2023? That's kind of question number one. Separately, you guys have a lot of kind of interesting phase I, phase II studies that you're currently, you know, starting kind of next year. Would be keen to understand how you're thinking about, kind of ballpark R&D costs kind of into next year. Thank you.
Yeah. Thank you. Very, very important question. I'll start with the second one, and then I'll hand over to Dr. Karakunnel. I think it's probably important to also remind you that our strategy is really to develop proof of concept, but at the same time, partner whenever it makes sense to do so, even at a later stage. Fact of the matter is that we have, you know, development program with AstraZeneca around monalizumab, but we have room within our finances to deliver our own clinical development program and our own phase I, II program, both for lacutamab but also for our anti-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 clinical trials with the limitations that you know in this field, a lot of competition. We are not only competing for the same patient, but sometimes it's challenging within the COVID environment. However, I think it's now more easier for an anti-CD73 to be developed given you know the proof of concept that AstraZeneca has made in the COAST trial.
Similarly for the pediatric 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, you know, case for further development in pediatric T-cell lymphoma. As you know, we are doing this development in two ways. A company-sponsored trial testing the agents in monotherapy in a sort of phase I-B trial in second-line relapse PTCL, essentially in the U.S. We have a second trial that is mainly in Europe that is sponsored by the LYSA group, and it's a randomized phase II trial testing the combination with immunotherapies.
I hope it addresses your question about and within the ability to execute on these two programs.
Indeed it does, Mondher. Thank you.
Thank you. Sonia Quaratino, can you provide a refresh on our registration strategy and path to market strategy for lacutamab and the data we generate in Sézary and beyond Sézary in MF?
Yeah, definitely. In regards to question number 1, you know, 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 anticipating preliminary data in 2022, and recruitment's on track right now. Our final data is expected in 2023. The potential for the SS, for the Sézary syndrome to be a candidate is pivotal. The cohort in Sézary syndrome can be a pivotal cohort. Just keeping in mind, we do have Fast Track designation in the U.S. and PRIME designation in the EU for potential for proactive support from the regulatory authorities and for accelerated assessments.
At least right now, it's too early to speculate on a potential launch timeline, and we'll make sort of data-driven decisions and follow through with these discussions as we continue to speak with the regulatory authorities.
Thank you.
As a reminder, if you would like to ask a question today, please press star followed by the number one on your telephone keypad. Our next question comes from Olga Smolentseva from Bryan, Garnier & Co. Please go ahead. Your line is now open.
Good afternoon, guys, and thank you for taking my questions. I have a few on IPH6101. Basically multiple therapeutic modalities that target CD123 did not achieve adequate risk-benefit ratio. Starting from anti-CD123 antibodies to bispecifics and ADCs. For you, what maybe are the key differentiating factors for NK cell engagers to sort of balance risk-benefit ratio in this context?
Thank you, Olga. I'm gonna hand over the question to Yannis Morel, who is leading the portfolio strategy and provide more color on the IPH6101 development. Yannis.
Yes, I think that the two 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 potent killing on the AML blood from patients and irrespective of the subset of the patients. We found out that some bloods are resistant to killing by a traditional antibody inducing ADCC antibody because of the expression of some Fc gamma receptor on the IM. That's the first one, meaning that we can potentially have efficacy in a broader subset of population of patients in AML.
The other key differentiating factor that you can see in the data that we have obtained both in non-human primates, but also in vitro using human cells and comparing our NK cell engager to a 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, meaning that we can potentially dose pretty high the molecule without inducing a systemic side effect of the unwanted cytokine release. Which is, by the way, one of the limitations for the T cell engager.
You may have noted that, for example, very recently, Novartis terminated their agreement with Xencor, and Xencor is not pursuing the T cell engager in the same target, mainly for this kind of reason of dosing.
Thank you, Yannis.
Thanks. That's very helpful.
Maybe considering.
Yeah.
Recent data from competitor in AML, sort of pointing towards a need for improved proliferation signaling. I'm just curious if tetra-specific NK cells, in this setting would sort of be a better choice.
I think it's probably too early to start, you know, to debate about the positioning of such antibody. It's clear that the medical need in this field is still extremely high. We are really 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 these drugs can play. From preclinical data and the package that we developed with our partner is quite convincing and of course convincing Sanofi to select our format and to move it into the clinic.
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, as single agent, but more important, as you can get in combination with other key standard treatment in AML in various subtype of this disease.
That's very helpful. Thank you. Congratulations on the progress.
Thank you. Operator, any more questions?
We currently have no further questions, so I'll hand back to Mondher Mahjoubi for closing remarks.
Thank you very much. As you can tell, collectively, we are really driving value across our business. Incrementally, I think we are advancing our goal to deliver innovative medicine to patients. We look forward to keeping you updated on our progress and thank you for your interest in Innate. Have a good day.
This now concludes today's call. Thank you for joining. You may now disconnect your line.