Joyson Karakunnel
Analyst · Daina Graybosch from SVB Leerink
Thank you, Mondher. On Slide 7, let me start with our first-in-class humanized monoclonal antibody that targets immune receptor KIR3DL2. As you may remember, KIR3DL2 is an inhibitory receptor found in approximately 65% of patients across all cutaneous T cell output. In the TELLOMAK trial, cohort 1 recruiting Sezary syndrome patients could potentially be a pivotal cohort. For mycosis fungoides, we have cohorts 2 and 3, which have been presented previously and are testing the hypothesis of non-expressors and expressors of KIR3DL2 using the frozen companion diagnostic assay. As expected, our scientific hypothesis confirmed -- was confirmed in cohort 2, high global response rates in comparison to the benchmark and the non-expressing cohort, a low global response rate in the non-expressing cohort. Recently we opened the all-comers cohort to further evaluate our FFPE companion diagnostic, which is being considered for late-stage trials. This cohort is not expected to impact timelines for the readout of the trial, and the companion diagnostic data will aid further in the development of the program. On Slide 8, let me summarize the progress we are making with lacutamab. We are pursuing a fast-to-market strategy for lacutamab in the niche setting of Sezary syndrome where lacutamab was granted U.S. Fast Track designation and Prime designation in 2020. We have expanded past Sezary syndrome to mycosis fungoides, where we have seen encouraging preliminary data from our Phase II trial. For the Sezary syndrome cohort, enrollment is on track, and we will still expect to be able to report top line preliminary data in the second half of 2022. For the mycosis fungoides cohort enrollment is on track, and we still expect to be able to report top line preliminary data in the second half of 2022. Finally, we are advancing into peripheral T-cell lymphoma in the monotherapy and combination trials in the relapse setting. On Slide 9, I would like to update you on monalizumab. To remind you, monalizumab is an anti-NKG2A, which acts upon a checkpoint pathway to potential NK cell activation that we have licensed to AstraZeneca for oncology. There are currently 2 ongoing AstraZeneca sponsored Phase III trials with monalizumab. One in combination with cetuximab in head and neck cancer, and one in combination with anti-PDL-1 durvalumab in lung cancer. On this slide, you can see an overview of the late-stage development plan for monalizumab in lung cancer. As mentioned, based on the AstraZeneca sponsored Phase II COAST data, AstraZeneca commenced PACIFIC-9, a Phase III trial evaluating the combination of either monalizumab or oleclumab plus durvalumab in the unresectable Stage III non-small cell lung cancer setting that had not progressed after concurring chemo radiation therapy. For the Phase II COAST study, the 3 arms evaluated the combination of durvalumab plus monalizumab and durvalumab plus oleclumab, AstraZeneca's anti-CD73. As published recently in the Journal of Clinical Oncology by AstraZeneca, after a median follow-up of 11.5 months, the results of the interim analysis showed a hazard ratio of 0.42 for durvalumab plus monalizumab versus 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% respectively. Although the small numbers in a PFS exploratory subgroup analysis, monalizumab with durvalumab demonstrated a trend favoring the combination in tumors with high HLA-E and NKG2A expression and supporting the mechanistic rationale for the combination. We are also pleased to see that AstraZeneca sponsored NeoCOAST data was presented at AACR Annual Meeting with initial signals that led to AstraZeneca's decision to start the NeoCOAST-2 study. NeoCOAST-2 is a Phase II study in Stages IIA to IIIA non-small cell lung cancer that includes a treatment arm with monalizumab in combination with durvalumab and chemotherapy. On Slide 10, moving to head and neck cancer. We presented data from cohort 3 of the Phase II trial at ESMO-IO in December of 2021 for the triplet of monalizumab plus durvalumab plus cetuximab in first-line head and neck cancer. The data demonstrated antitumor activity in the first study to evaluate this chemo-free triplet combination in the first-line recurrent or metastatic head and neck cancer setting. As a reminder, the standard of care is based on the KEYNOTE-048 trial. The approval is for pembrolizumab monotherapy and CPS greater than or equal to one in pembro plus chemo in all-comer patients. We continue to collaborate with our partner, AstraZeneca, on potential next steps for this program. The Phase III INTERLINK-I trial of monalizumab plus cetuximab in IO-pretreated head and neck cancer is ongoing with final data expected in 2024. We look to work further with our partners, AstraZeneca, on this potential niche. On Slide 11, I would like to highlight the progress of our assets targeting the adenosine pathway, which is increasingly recognized as critical in tumor immune suppression and 2 approaches we at Innate are taking. Our anti-CD39 IPH5201 in collaboration with AstraZeneca has concluded the Phase I trial in solid tumors in combination with durvalumab, and we expect the data in 2023. In the meantime, we are in discussions with AstraZeneca as the next steps for this program. For our anti-CD73 IPH5301, an investigator-sponsored Phase I trial has started, where the IST is exploring a differentiated approach, combining our anti-CD73 with trastuzumab in HER2-positive cancers. We look forward to further updates from this clinical program next year. I will now hand over to Yannis to cover our NK platform.