MSI is a molecular indicator of defective DNA mismatch repair (dMMR). The MSI/dMMR status is observed in all tumor types, representing notably 5% of metastatic colorectal cancers (mCRC), 25% of advanced endometrial cancer and 8% of metastatic gastric cancer.
MSI/dMMR cancers are highly immunogenic. MSI/dMMR tumors are characterized by a high tumor mutational burden with highly immunogenic neoantigens. These tumors are associated with an upregulation of immune checkpoints (PD1, PDL1, CTLA4, etc.) that protects MSI cancer cells from their hostile immune micro-environment, characterized by a high infiltration of activated cytotoxic T CD8+ and NK lymphocytes. Consequently, MSI/dMMR cancers are highly sensitive to ICIs, whatever the tumor location. MSI/dMMR status is a predictive biomarker for the efficacy of immunotherapy, regardless of the tumor type. Then, by several phase II and III studies The efficacy of immunotherapy has been demonstrated as front-line treatment for patients with chemotherapy-naive MSI/dMMR mCRC and gastric cancer. The phase III KEYNOTE-177 trial evaluating first-line treatment of pembrolizumab in patients with MSI/dMMR mCRC demonstrated its superiority over first-line chemotherapy, with a significant improvement of health-related quality of life. At final analysis, the median follow-up was 44.5 months. Median PFS was 16.5 versus 8.2 months (HR = 0.59; 95%CI 0.45-0.79). The hazard ratio favored pembrolizumab versus chemotherapy with a trend toward reduction in the risk of death (HR 0.74; 95% CI, 0.53-1.03; P=0.0359), despite a 60% effective crossover rate. Pembrolizumab has been approved by the FDA and the EMA for patients with newly diagnosed MSI/dMMR mCRC and is now the standard of care for this population. Also, the phase III CHECKMATE-649 trial reveal that the Combination of immunotherapy and cytotoxic chemotherapy is the new standard of care for patients with newly diagnosed metastatic oesogastric cancer. Importantly, results of the CHECKMATE-649 are outstanding for the subgroup population of MSI/dMMR gastric cancer patients (N = 44). Indeed, the unstratified hazard ratio for OS with nivolumab plus chemotherapy versus chemotherapy alone was 0.33 (95% CI 0.12-0.87) for patients with MSI/dMMR tumors. All in all, ICIs are the standard of care in first-line setting for patients with mCRC or metastatic oesogastric cancer. Besides, several phase II studies suggest that ICI combinations might overcome primary resistance to anti-PD1 monotherapy These data justify the development of bispecific monoclonal antibodies targeting both PD1 and CTLA4 such as MEDI5752. MEDI5752 has been developed based on the observation that there is a higher expression of PD-1/CTLA-4 on tumor resident versus peripheral T cells. Preclinical data show MEDI5752 fully suppresses PD-1 and preferentially inhibits CTLA-4 in the tumor versus the periphery, which is meant to uncouple CTLA-4 dependant peripheral toxicity from antitumor activity Natural killer cells are integral to the functioning of the innate immune system and play an important role in innate antitumor immunity. There is a growing body of evidence for targeting the NKG2A/HLA-E axis in combination with other ICIs to sensitize tumors to ICI therapy. NKG2A recognizes the non-classical HLA class I molecule HLA-E. The NKG2A receptor is found on peripheral NK cells and subsets of T cells in cancer patients. It is also present in tumor-infiltrating NK and cytotoxic T cells. Importantly, NK cells and the NKG2A/HLA-E axis play a crucial role in MSI/dMMR tumors. Therefore, a combined blockade of non-redundant checkpoint pathways to unleash NK and T cells seems particularly promising for MSI/dMMR neoplasms. Monalizumab specifically binds and blocks the inhibitory receptor NKG2A. Monalizumab has been investigated in combination with ibrutinib (in chronic lymphoid leukemia), cetuximab +/- durvalumab (in squamous cell carcinoma of the head and neck, and in solid tumors), durvalumab +/- FOLFOX (in solid tumors). In the first-in-human dose escalation of monalizumab plus durvalumab, a manageable toxicity profile was shown.
Taken together, these data provide a strong rational to combine an inhibitor of the NKG2A/HLA-E axis with a bispecific monoclonal antibody targeting both PD1 and CTLA4 for patients with metastatic MSI/dMMR cancers.

Start Date01 Dec 2023

Sponsor / Collaborator

Assistance Publique des Hôpitaux de Paris SA

NCT05903092 / RecruitingPhase 2

A Phase II Trial of MOnaliZumab in Combination With durvAlumab (MEDI4736) Plus Platinum-based chemotheRapy for First-line Treatment of Extensive Stage Small Cell Lung Cancer (MOZART)

The study treatment will consist of a platinum drug (carboplatin or cisplatin per investigator's choice) plus etoposide plus durvalumab plus monalizumab every 3 weeks for 4 cycles. After 4 cycles, subjects will continue maintenance treatment with durvalumab plus monalizumab every 4 weeks until disease progression, unacceptable toxicity, decision to stop study treatment, or withdrawal of consent. Patients who have received one prior cycle of treatment before enrolling on the study will receive a total of 4 cycles with monalizumab, durvalumab, and chemotherapy. There will be a safety lead-in phase, including 6 to 12 patients, to confirm the safety of the proposed dose of monalizumab to use in combination with chemotherapy and durvalumab.

Start Date26 Sep 2023

Sponsor / Collaborator

Hoosier Cancer Research Network

[+2]

CTR20221538 / RecruitingPhase 3

一项评价度伐利尤单抗 + Oleclumab和度伐利尤单抗 + Monalizumab用于根治性含铂药物同步放化疗后未进展的局部晚期（III期）、不可切除非小细胞肺癌（NSCLC）患者的双盲、安慰剂对照、随机、多中心、国际、III期研究（PACIFIC-9）

[Translation] An evaluation of durvalumab + Oleclumab and durvalumab + Monalizumab in locally advanced (stage III), unresectable non-small cell lung cancer (NSCLC) that has not progressed after curative platinum-based concurrent chemoradiotherapy A double-blind, placebo-controlled, randomized, multicenter, international, phase III study in patients (PACIFIC-9)

主要目的旨在为证明在既往含铂cCRT治疗后未发生疾病进展的不可切除III期NSCLC受试者中度伐利尤单抗 + Oleclumab优效于度伐利尤单抗 + 安慰剂; 以及证明在既往含铂cCRT治疗后未发生疾病进展的不可切除III期NSCLC受试者中度伐利尤单抗 + Monalizumab优效于度伐利尤单抗 + 安慰剂。

[Translation]

The primary objective is to demonstrate the superiority of moderate valumab + oleclumab over durvalumab + placebo in subjects with unresectable stage III NSCLC who have not progressed after previous platinum-containing cCRT; And demonstrated moderate superiority of valumab + monalizumab over durvalumab + placebo in subjects with unresectable stage III NSCLC who had not progressed after previous platinum-containing cCRT therapy.

Start Date15 Aug 2022

Sponsor / Collaborator

AstraZeneca Global R&D (China) Co., Ltd.

[+2]

100 Clinical Results associated with Monalizumab

100 Translational Medicine associated with Monalizumab

100 Patents (Medical) associated with Monalizumab

Literatures (Medical) associated with Monalizumab

01 May 2024·Combinatorial Chemistry & High Throughput Screening

A Novel Natural Killer Cell-related Gene Signature for Improving the Prediction of Prognosis and Immunotherapy Response in Bladder Cancer

Article

Author: Wei, Xifeng ; Ma, Xudong ; Li, Shuai ; Liu, Ranlu ; Yang, Guanghua

Background:Bladder cancer (BLCA) is a commonly diagnosed cancer worldwide that exhibits high rates of recurrence and metastasis. Immunotherapy is increasingly being recognised in the clinical management of bladder cancer. In addition, the prospect of developing Natural Killer (NK) cell-related immunotherapy is promising in BLCA.Methods:We established and verified a prognostic signature based on NK cell-related gene expression. We then calculated the NKscore of BLCA samples and correlated it with the clinical outcomes, molecular subtypes of BLCA, tumour microenvironment (TME), and predicted efficacy of immune checkpoint inhibitors (ICI) and chemotherapy drugs to thoroughly explore the implications of the NKscore. Finally, the role of the NK signature gene HECTD1 in BLCA was verified by Quantitative Real-time PCR, Cell Counting Kit-8 Assay (CCK-8), Transwell Assay and Colony Formation Experiment.Results:We analysed NK cell-associated genes and identified six genes with significant prognostic relevance. A high NK score significantly represents a worse prognosis. NKscore was significantly correlated with seven types of classical molecular subtype classifications of BLCA. In addition, NKscore positively correlates with NK-related immune checkpoints, suggesting that emerging NK cell immune checkpoint inhibitors, such as monalizumab, may have potential therapeutic promise for patients with high NKscore. The results of the T cell inflamed score (TIS) and tumour immune dysfunction exclusion (TIDE) score confirmed the suitability of immunotherapy for patients with a high NK score. Likewise, patients with a high NK score may be more suitable for several significant chemotherapeutic drugs. Functional experiments showed that the knockdown of HECTD1 significantly attenuated the proliferation, migration, and invasion ability of tumour cells.Conclusion:To sum up, the capability of our signature to predict prognosis and immunotherapy response was robust. Hopefully, these results will provide new insights for BLCA research and patient immunotherapy.

01 Feb 2024·Journal for ImmunoTherapy of Cancer

Phase 1/2 study of monalizumab plus durvalumab in patients with advanced solid tumors

Article

Author: Das, Mayukh ; Kourtesis, Panagiotis ; Hellmann, Matthew D ; Palmer, Doug C ; Standifer, Nathan E ; Carneiro, Benedito A ; Banerjee, Susana ; Ascierto, Maria L ; Wang, Ding ; Naidoo, Jarushka ; Alonso-Gordoa, Teresa ; Diamond, Jennifer R ; Patel, Sandip P ; Cheng, Lin-Yang

BackgroundThe combination of monalizumab (anti-NKG2A/CD94) and durvalumab (anti-programmed death ligand-1) may promote antitumor immunity by targeting innate and adaptive immunity. This phase 1/2 study of monalizumab and durvalumab evaluated safety, antitumor activity, and pharmacodynamics in patients with advanced solid tumors.Main bodyImmunotherapy-naïve patients aged ≥18 years with advanced disease, Eastern Cooperative Oncology Group performance status of 0–1, and 1–3 prior lines of systemic therapy in the recurrent/metastatic setting were enrolled. In part 1 (dose escalation), patients received durvalumab 1500 mg every 4 weeks (Q4W) with increasing doses of monalizumab Q2W/Q4W (n=15). Dose expansion in part 1 included patients with cervical cancer (n=15; durvalumab 1500 mg Q4W and monalizumab 750 mg Q2W) or metastatic microsatellite stable (MSS)-colorectal cancer (CRC) (n=15; durvalumab 1500 mg Q4W and monalizumab 750 mg Q4W). In part 2 (dose expansion), patients with MSS-CRC (n=40), non-small cell lung cancer (NSCLC; n=20), MSS-endometrial cancer (n=40), or ovarian cancer (n=40) received durvalumab 1500 mg Q4W and monalizumab 750 mg Q2W. The primary endpoint was safety. Secondary endpoints included antitumor activity per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1). Exploratory analyses included assessment of T-cell and natural killer (NK) cell activation and proliferation in peripheral blood and the tumor microenvironment (TME). The study enrolled 185 patients (part 1, 45; part 2, 140). No dose-limiting toxicities were observed and the maximum tolerated dose was not reached. In part 2, the most common treatment-related adverse events were fatigue (12.1%), asthenia (9.3%), diarrhea (9.3%), pruritus (7.9%), and pyrexia (7.1%). In the expansion cohorts, response rates were 0% (cervical), 7.7% (MSS-CRC), 10% (NSCLC), 5.4% (ovarian), and 0% (MSS-endometrial). Sustained NK cell activation, CD8+T-cell proliferation, increased serum levels of CXCL10 (C-X-C motif chemokine ligand 10) and CXCL11, and increased tumor infiltration of CD8+and granzyme B+cells were observed.ConclusionsAlthough efficacy was modest, monalizumab plus durvalumab was well tolerated and encouraging immune activation was observed in the peripheral blood and TME.Trial registration numberNCT02671435.

01 Nov 2023·Cancer Discovery

Neoadjuvant Durvalumab Alone or Combined with Novel Immuno-Oncology Agents in Resectable Lung Cancer: The Phase II NeoCOAST Platform Trial

Article

Author: García-Campelo, Rosario ; Hussein, Maen ; Hamid, Oday ; Anagnostou, Valsamo ; Tan, Tze Heng ; Cascone, Tina ; Gopalakrishnan, Vancheswaran ; Soo-Hoo, Yee ; Mazieres, Julien ; Spigel, David R ; Rodriguez-Canales, Jaime ; McGrath, Lara ; Forde, Patrick M ; Oliveira, Julio ; Grenga, Italia ; Sellman, Bret R ; Spira, Alexander I ; Zheng, Ying ; Kar, Gozde ; Kumar, Rakesh ; Blando, Jorge ; Spicer, Jonathan D ; Cheng, Lin-Yang ; Yau, Edwin H ; Surace, Michael ; Mager, Raymond ; Weder, Walter ; Daniel, Davey B

AbstractNeoadjuvant chemoimmunotherapy improves pathologic complete response rate and event-free survival in patients with resectable non–small cell lung cancer (NSCLC) versus chemotherapy alone. NeoCOAST was the first randomized, multidrug platform trial to examine novel neoadjuvant immuno-oncology combinations for patients with resectable NSCLC, using major pathologic response (MPR) rate as the primary endpoint. Eighty-three patients received a single cycle of treatment: 26 received durvalumab (anti–PD-L1) monotherapy, 21 received durvalumab plus oleclumab (anti-CD73), 20 received durvalumab plus monalizumab (anti-NKG2A), and 16 received durvalumab plus danvatirsen (anti-STAT3 antisense oligonucleotide). MPR rates were higher for patients in the combination arms versus durvalumab alone. Safety profiles for the combinations were similar to those of durvalumab alone. Multiplatform immune profiling suggested that improved MPR rates in the durvalumab plus oleclumab and durvalumab plus monalizumab arms were associated with enhanced effector immune infiltration of tumors, interferon responses and markers of tertiary lymphoid structure formation, and systemic functional immune cell activation.Significance:A neoadjuvant platform trial can rapidly generate clinical and translational data using candidate surrogate endpoints like MPR. In NeoCOAST, patients with resectable NSCLC had improved MPR rates after durvalumab plus oleclumab or monalizumab versus durvalumab alone and tumoral transcriptomic signatures indicative of augmented immune cell activation and function.See related commentary by Cooper and Yu, p. 2306.This article is featured in Selected Articles from This Issue, p. 2293

News (Medical) associated with Monalizumab

14 May 2024

·www.biospace.com

Innate Pharma Reports First Quarter 2024 Business Update and Financial Results

First preclinical data set for IPH45, a pre-IND anti-Nectin-4 Antibody Drug Conjugate, presented as an oral presentation at AACR 2024 Progression of Sanofi-developed NK Cell Engager SAR443579/IPH6101 to Phase 2 in blood cancers Five ASCO Annual Meeting 2024 abstracts: Final TELLOMAK Phase 2 data for lacutamab in Mycosis Fungoides Two posters on IPH6501, Innate's second generation ANKET® in B‑cell Non-Hodgkin's Lymphoma AstraZeneca to present poster on updated results for monalizumab from Phase 2 stage III unresectable NSCLC trial Monalizumab SCLC Phase 2 MOZART trial poster Cash position of €113.9 million1 as of March 31, 2024 (not including the €4.0 million payment to be received from Sanofi), anticipated cash runway into end 2025 Conference call to be held today at 2:00 p.m. CEST / 8:00 a.m. EDT MARSEILLE, France--(BUSINESS WIRE)-- Regulatory News: Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) (“Innate” or the “Company”) today reported its consolidated financial results for the quarter ending March 31, 2024. “We are executing our strategy of building on our partnered drug candidates while advancing our next generation of proprietary medicines,” said Hervé Brailly, Chief Executive Officer ad interim of Innate Pharma. “Our second generation ANKET®, IPH6501 began clinical development for NHL. We presented preclinical data for IPH45, our Nectin-4 ADC, at the recently held AACR Annual Meeting. Our partner Sanofi also advanced SAR443579, a tri-functional NK Cell Engager targeting CD123, to Phase 2 in blood cancer. We expect to have several data presentations at ASCO, including data from the TELLOMAK Phase 2 trial with lacutamab in mycosis fungoides, as we prepare to submit an IND for IPH45 later this year.” Webcast and conference call will be held today at 2:00pm CEST (8:00am EDT) The live webcast will be available at the following link: Participants may also join via telephone using the following registration link: This information can also be found on the Investors section of the Innate Pharma website, . A replay of the webcast will be available on the Company website for 90 days following the event. 1 Including short term investments (€21.3 million) and non-current financial instruments (€10.1 million). Pipeline highlights: Lacutamab (anti-KIR3DL2 antibody): Cutaneous T Cell lymphoma TELLOMAK is a global, open-label, multi-cohort Phase 2 clinical trial evaluating lacutamab in patients with Sézary syndrome and mycosis fungoides (MF). Top-line results in MF patients will be presented at the ASCO Annual Meeting 2024 being held May 31 – June 4 in Chicago. Title of the abstract is: Lacutamab in patients with relapsed and/or refractory mycosis fungoides: results from the TELLOMAK Phase 2 trial. The full abstract will be released at 5:00 PM ET on Thursday, May 23, 2024 on the ASCO Annual Meeting website. In January 2024, Innate announced that the US Food and Drug Administration (FDA) has lifted the partial clinical hold previously placed on the lacutamab IND on October 2023 following a patient death in the TELLOMAK study. The FDA decision to lift the partial clinical hold is based on the FDA review of the fatal case which Innate, together with a steering committee of independent experts, determined to be related to aggressive disease progression and lacutamab unrelated. Peripheral T Cell lymphoma (PTCL) The Phase 2 KILT (anti-KIR in T Cell Lymphoma) trial, an investigator-sponsored, randomized controlled trial led by the Lymphoma Study Association (LYSA) to evaluate lacutamab in combination with chemotherapy GEMOX (gemcitabine in combination with oxaliplatin) versus GEMOX alone in patients with KIR3DL2-expressing relapsed/refractory PTCL is ongoing and continues to recruit patients. ANKET® (Antibody-based NK cell Engager Therapeutics): ANKET® is Innate’s proprietary platform for developing next-generation, multi-specific NK cell engagers to treat certain types of cancer. Innate’s pipeline includes five public drug candidates born from the ANKET® platform: SAR443579 (SAR’579/IPH6101) (CD123-targeted), SAR445514 (SAR’514/IPH6401) (BCMA-targeted), IPH62 (B7-H3-targeted), IPH67 (target undisclosed, solid tumors) and tetra-specific IPH6501 (CD20-targeted with IL‑2v). Several other undisclosed proprietary preclinical targets are being explored. IPH6501 (proprietary) IPH6501 is Innate’s proprietary CD20-targeted IL-2v bearing second-generation ANKET®. Innate will present 2 posters on IPH6501 at the upcoming ASCO Annual Meeting 2024, being held from May 31 to June 4 in Chicago. Titles of the abstract are: A Phase 1/2, Open-Label, Multicenter Trial Investigating the Safety, Tolerability, and Preliminary Antineoplastic Activity of IPH6501 in Patients With Relapsed and/or Refractory CD20-expressing Non-Hodgkin Lymphoma Preclinical assessment of IPH6501, a first-in-class IL2v-armed tetraspecific NK Cell Engager directed against CD20 for R/R B-NHL, in comparison to a CD20-targeting T Cell Engager The full abstracts will be released at 5:00 PM ET on Thursday, May 23, 2024 on the ASCO Annual Meeting website. In March 2024 the first patient was dosed in the Phase 1/2 clinical trial evaluating IPH6501 in B cell Non-Hodgkin’s lymphoma (B-NHL). The study is planned to enroll up to 184 patients. SAR443579, SAR445514, IPH62 and IPH67 (under development by Sanofi) SAR443579/IPH6101 The Phase 1/2 clinical trial, currently under development, by Sanofi is progressing well, evaluating SAR443579 / IPH6101, a trifunctional anti-CD123 NKp46×CD16 NK cell engager and ANKET® platform lead asset, in patients with relapsed or refractory acute myeloid leukemia (R/R AML), B-cell acute lymphoblastic leukemia (B-ALL) or high-risk myelodysplastic syndrome (HR-MDS). In April 2024, Sanofi advanced SAR443579 / IPH6101, to the Phase 2 dose expansion of the trial. Under the terms of the 2016 research collaboration with Sanofi, the progression to the dose expansion part of the trial has triggered a milestone payment from Sanofi to Innate of €4m (which has been booked as revenue in the first quarter but had not been received from Sanofi in the quarter, and has therefore not been included in the cash position). SAR445514/IPH6401 The Sanofi led Phase 1/2 clinical trial with SAR’514 / IPH6401, a trifunctional anti-BCMA Nkp46xCD16 NK cell engager, in patients with Relapsed/Refractory Multiple Myeloma and Relapsed/Refractory Light-chain Amyloidosis is ongoing. IPH62 IPH62 is a NK cell engager program targeting B7-H3 from Innate’s ANKET® platform under development. Upon candidate selection, Sanofi will be responsible for all development, manufacturing and commercialization. IPH67 IPH67 is a NK cell engager program in solid tumors from Innate’s ANKET® platform under development. Following a research collaboration period, Sanofi will be responsible for all development, manufacturing and commercialization. Sanofi still retains the option of one additional ANKET® target under the terms of the 2022 research collaboration and license agreement. Antibody Drug Conjugates: Innate develops different approaches for the treatment of cancer utilizing its antibody engineering capabilities to deliver novel assets, with its innovative ANKET® platform and is also exploring Antibody Drug Conjugates (ADC) formats. Beyond its proprietary programs, Innate has an ongoing agreement with Takeda on ADCs. IPH45 (Nectin-4 ADC): IPH45 is Innate’s proprietary and differentiated exatecan-Antibody Drug Conjugate (ADC) targeting Nectin-4. First preclinical data were presented in an oral presentation at the American Association for Cancer Research (AACR) Annual Meeting 2024. In preclinical studies, IPH45 shows anti-tumor efficacy in vivo, in Nectin-4 expressing tumors including in Enfortumab Vedotin (EV) refractory models. Importantly, IPH45 shows stronger activity than EV, in multiple urothelial carcinoma patient-derived xenografted (PDX) mice models, across Nectin-4 high and Nectin-4 low expression levels. In addition, IPH45 has anti-tumor activity in combination with anti-PD1 treatment in PD-1 resistant model in vivo and has a favorable safety pro relevant animal toxicology models. IPH45 continues towards IND filing in 2024. Monalizumab (anti-NKG2A antibody), partnered with AstraZeneca: The Phase 3 PACIFIC-9 trial run by AstraZeneca evaluating durvalumab (anti-PD-L1) in combination with monalizumab or AstraZeneca’s oleclumab (anti-CD73) in patients with unresectable, Stage III non-small cell lung cancer (NSCLC) who have not progressed following definitive platinum-based concurrent chemoradiation therapy (CRT) is ongoing. AstraZeneca will present a poster at ASCO titled: “Updated results from COAST, a phase 2 study of durvalumab (D) ± oleclumab (O) or monalizumab (M) in patients (pts) with stage III unresectable non-small cell lung cancer (uNSCLC).” A poster at ASCO will also be presented titled “A phase II trial of monalizumab in combination with durvalumab (MEDI4736) plus platinum-based chemotherapy for first-line treatment of extensive stage small cell lung cancer (MOZART): Hoosier Cancer Research Network LUN21-530 study.” IPH5201 (anti-CD39), partnered with AstraZeneca: The MATISSE Phase 2 clinical trial conducted by Innate in neoadjuvant lung cancer for IPH5201, an anti-CD39 blocking monoclonal antibody developed in collaboration with AstraZeneca, is ongoing and recruitment is on track. IPH5301 (anti-CD73): The investigator-sponsored CHANCES Phase 1 trial of IPH5301 by Institut Paoli-Calmettes is ongoing. Corporate Update: Early January 2024, two new Executive Board members were appointed. Arvind Sood, Executive Vice President (EVP), President of US Operations, Dr Sonia Quaratino, EVP, Chief Medical Officer, joining Hervé Brailly, interim Chief Executive Officer and Yannis Morel, EVP, appointed Chief Operating Officer. In connection with Innate’s previous announcement that it had established an at-the-market (“ATM”) program, on January 16, 2024 Innate filed a new Registration Statement on Form F-3 (Registration No. 333-276164). On February 6, 2024, Innate filed a prospectus supplement relating to its previously established ATM program, pursuant to which it may, from time to time, offer and sell to eligible investors a total gross amount of up to $75 million of American Depositary Shares (“ADS”). Each ADS represents one ordinary share of Innate. As of March 31, 2024, no sales have been made under the program. Financial Results: Cash, cash equivalents and financial assets of the Company amounted to €113.9 million as of March 31, 2024. At the same date, financial liabilities amounted to €37.7 million. Cash, cash equivalents and financial assets as of March 31, 2024 do not include the €4.0 million payment to be received from Sanofi. Revenues for the first three months of 2024 amounted to €6.6 million (€26.0 million for the same period in 2023). For the three-month period, ended March 31, 2024, revenue from collaboration and licensing agreements mainly results from the partial or entire recognition of the proceeds received pursuant to the agreements with AstraZeneca and Sanofi. About Innate Pharma Innate Pharma S.A. is a global, clinical-stage biotechnology company developing immunotherapies for cancer patients. Its innovative approach aims to harness the innate immune system through therapeutic antibodies and its ANKET® (Antibody-based NK cell Engager Therapeutics) proprietary platform. Innate’s portfolio includes lead proprietary program lacutamab, developed in advanced form of cutaneous T cell lymphomas and peripheral T cell lymphomas, monalizumab developed with AstraZeneca in non-small cell lung cancer, as well as ANKET® multi-specific NK cell engagers to address multiple tumor types. Innate Pharma is a trusted partner to biopharmaceutical companies such as Sanofi and AstraZeneca, as well as leading research institutions, to accelerate innovation, research and development for the benefit of patients. Headquartered in Marseille, France with a US office in Rockville, MD, Innate Pharma is listed on Euronext Paris and Nasdaq in the US. Learn more about Innate Pharma at and follow us on LinkedIn and X. Information about Innate Pharma shares ISIN code Ticker code LEI FR0010331421 Euronext: IPH Nasdaq: IPHA 9695002Y8420ZB8HJE29 Disclaimer on forward-looking information and risk factors This press release contains certain forward-looking statements, including those within the meaning of the Private Securities Litigation Reform Act of 1995. The use of certain words, including “believe,” “potential,” “expect” and “will” and similar expressions, is intended to identify forward-looking statements. Although the company believes its expectations are based on reasonable assumptions, these forward-looking statements are subject to numerous risks and uncertainties, which could cause actual results to differ materially from those anticipated. These risks and uncertainties include, among other things, the uncertainties inherent in research and development, including related to safety, progression of and results from its ongoing and planned clinical trials and preclinical studies, review and approvals by regulatory authorities of its product candidates, the Company’s commercialization efforts and the Company’s continued ability to raise capital to fund its development. For an additional discussion of risks and uncertainties which could cause the company's actual results, financial condition, performance or achievements to differ from those contained in the forward-looking statements, please refer to the Risk Factors (“Facteurs de Risque") section of the Universal Registration Document filed with the French Financial Markets Authority (“AMF”), which is available on the AMF website or on Innate Pharma’s website, and public filings and reports filed with the U.S. Securities and Exchange Commission (“SEC”), including the Company’s Annual Report on Form 20-F for the year ended December 31, 2023, and subsequent filings and reports filed with the AMF or SEC, or otherwise made public, by the Company. This press release and the information contained herein do not constitute an offer to sell or a solicitation of an offer to buy or subscribe to shares in Innate Pharma in any country. View source version on businesswire.com: Contacts Investors Innate Pharma Henry Wheeler Tel.: +33 (0)4 84 90 32 88 Henry.wheeler@innate-pharma.fr Media Relations NewCap Arthur Rouillé Tel.: +33 (0)1 44 71 00 15 innate@newcap.eu Source: Innate Pharma SA View this news release online at:

Phase 2License out/inPhase 1

13 May 2024

·www.fiercepharma.com

As Bristol Myers reveals trial failure, AstraZeneca's Imfinzi stays king in stage 3 lung cancer

The Bristol Myers setback follows another similar one by AstraZeneca's Imfinzi. Another attempt at improving upon AstraZeneca’s Imfinzi in stage 3, unresectable non-small cell lung cancer (NSCLC) has gone up in flames. The latest failure comes from a phase 3 trial conducted by Bristol Myers Squibb. The company’s Opdivo, used with concurrent chemoradiotherapy, followed by Opdivo plus BMS’ Yervoy, failed to beat Imfinzi maintenance in unresectable stage 3 NSCLC, BMS said Friday. The Imfinzi regimen features chemoradiation alone followed by Imfinzi during the maintenance phase of treatment. Approved by the FDA in early 2018, unresectable stage 3 NSCLC has been Imfinzi’s main indication, and it’s where the AZ PD-L1 inhibitor is the standard of care for patients whose cancer has not progressed after chemoradiation. BMS tried to challenge AZ’s dominance by launching the phase 3 CheckMate-73L trial in 2019. The company figured that because chemoradiotherapy increases PD-L1 expression, concurrent immune checkpoint inhibition may improve outcomes. But, now, the study found the Opdivo-Yervoy-concurrent-chemoradiation regimen couldn’t extend the time before tumor progression or death versus the Imfinzi maintenance approach. The adverse events observed were generally consistent with the known profiles of each component in the combination, BMS said. The CheckMate-73L study features another arm testing Opdivo monotherapy during the maintenance phase. But because its primary endpoint measures progression-free survival for the Opdivo-Yervoy arm, the entire study is now considered negative. The study’s many secondary endpoints include overall survival for either experimental arm against Imfinzi and for the two Opdivo arms against each other. The BMS setback follows another similar one by Imfinzi itself. Because the current Imfinzi regimen is given only to patients who have not progressed after initial chemoradiotherapy, AZ had tried to expand the drug’s patient base by giving Imfinzi and chemoradiation concurrently. However, that regimen recently failed to beat Imfinzi maintenance in the phase 3 PACIFIC-2 trial. Besides those regimens, China’s CStone Pharmaceuticals in 2022 reported positive phase 3 results from the GEMSTONE-301 trial for its China-approved PD-L1 inhibitor Cejemly (sugemalimab) when used after chemoradiotherapy in unresectable stage 3 NSCLC. However, that study was conducted solely in China, and the drug was pitted against placebo, not Imfinzi, so the results are not considered meaningful for the U.S. market. Now, market watchers are turning their attention to Merck & Co.’s PD-1 king Keytruda. The phase 3 KEYLYNK-012 trial is testing concurrent use of chemoradiation and Keytruda, followed by Keytruda with or without AZ and Merck’s PARP inhibitor Lynparza, versus Imfinzi maintenance in unresectable stage 3 NSCLC. However, the regimen doesn’t look very promising after a pair of phase 3 flops for the PD-1/PARP combo in metastatic NSCLC. There’s also Roche’s PD-L1 inhibitor Tecentriq. The Swiss pharma is running the phase 3 SKYSCRAPER-03 trial pairing Tecentriq with the company’s closely watched TIGIT inhibitor tiragolumab in the maintenance setting following concurrent platinum-based chemoradiation. The trial finished enrollment about a year ago and bears a primary completion date this October, according to Roche. AZ isn’t giving up its expansion efforts, either. The PACIFIC-9 trial is evaluating Imfinzi together with either the company’s anti-CD73 antibody oleclumab or Innate Pharma-partnered anti-NKG2A antibody monalizumab as a maintenance therapy. A readout from that phase 3 study could be two years away.

Phase 3Clinical ResultDrug ApprovalImmunotherapyPhase 2

07 May 2024

·www.biospace.com

Innate Pharma Announces Conference Call and Webcast for Q1 2024 Business Update

MARSEILLE, France--(BUSINESS WIRE)-- Regulatory News: Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) (“Innate” or the “Company”), today announced that the Company will hold a conference call on Tuesday, May 14, 2024, at 2 p.m. CEST / 8 a.m. EDT, to give an update on business progress during the first quarter of 2024. Participants during the call will be: Hervé Brailly, Chief Executive Officer Sonia Quaratino, Executive Vice President, Chief Medical Officer Yannis Morel, Executive Vice President, Chief Operating Officer Frédéric Lombard, Senior Vice President, Chief Financial Officer Arvind Sood, Executive Vice President, President of US Operations Details for the Virtual Event The live webcast will be available at the following link: Participants may also join via telephone using the following registration link: This information can also be found on the Investors section of the Innate Pharma website, . A replay of the webcast will be available on the Company website for 90 days following the event. About Innate Pharma Innate Pharma S.A. is a global, clinical-stage biotechnology company developing immunotherapies for cancer patients. Its innovative approach aims to harness the innate immune system through therapeutic antibodies and its ANKET® (Antibody-based NK cell Engager Therapeutics) proprietary platform. Innate’s portfolio includes lead proprietary program lacutamab, developed in advanced form of cutaneous T cell lymphomas and peripheral T cell lymphomas, monalizumab developed with AstraZeneca in non-small cell lung cancer, as well as ANKET® multi-specific NK cell engagers to address multiple tumor types. Innate Pharma is a trusted partner to biopharmaceutical companies such as Sanofi and AstraZeneca, as well as leading research institutions, to accelerate innovation, research and development for the benefit of patients. Headquartered in Marseille, France with a US office in Rockville, MD, Innate Pharma is listed on Euronext Paris and Nasdaq in the US. Learn more about Innate Pharma at and follow us on X and LinkedIn. Information about Innate Pharma shares ISIN code FR0010331421 Ticker code Euronext: IPH Nasdaq: IPHA LEI 9695002Y8420ZB8HJE29 Disclaimer on forward-looking information and risk factors This press release contains certain forward-looking statements, including those within the meaning of the Private Securities Litigation Reform Act of 1995. The use of certain words, including “believe,” “potential,” “expect” and “will” and similar expressions, is intended to identify forward-looking statements. Although the company believes its expectations are based on reasonable assumptions, these forward-looking statements are subject to numerous risks and uncertainties, which could cause actual results to differ materially from those anticipated. These risks and uncertainties include, among other things, the uncertainties inherent in research and development, including related to safety, progression of and results from its ongoing and planned clinical trials and preclinical studies, review and approvals by regulatory authorities of its product candidates, the Company’s commercialization efforts and the Company’s continued ability to raise capital to fund its development. For an additional discussion of risks and uncertainties which could cause the company's actual results, financial condition, performance or achievements to differ from those contained in the forward-looking statements, please refer to the Risk Factors (“Facteurs de Risque") section of the Universal Registration Document filed with the French Financial Markets Authority (“AMF”), which is available on the AMF website or on Innate Pharma’s website, and public filings and reports filed with the U.S. Securities and Exchange Commission (“SEC”), including the Company’s Annual Report on Form 20-F for the year ended December 31, 2023, and subsequent filings and reports filed with the AMF or SEC, or otherwise made public, by the Company. This press release and the information contained herein do not constitute an offer to sell or a solicitation of an offer to buy or subscribe to shares in Innate Pharma in any country. View source version on businesswire.com: Contacts Investors Innate Pharma Henry Wheeler Tel.: +33 (0)4 84 90 32 88 Henry.wheeler@innate-pharma.fr Media Relations NewCap Arthur Rouillé Tel.: +33 (0)1 44 71 00 15 innate@newcap.eu Source: Innate Pharma SA View this news release online at:

ImmunotherapyClinical Study

100 Deals associated with Monalizumab

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Indication	Highest Phase	Country/Location	Organization	Date
Squamous cell carcinoma of head and neck metastatic	Phase 3	PH	AstraZeneca PLC	02 Oct 2020
Squamous cell carcinoma of head and neck metastatic	Phase 3	FR	AstraZeneca PLC	02 Oct 2020
Squamous cell carcinoma of head and neck metastatic	Phase 3	JP	AstraZeneca PLC	02 Oct 2020
Squamous cell carcinoma of head and neck metastatic	Phase 3	GB	AstraZeneca PLC	02 Oct 2020
Squamous cell carcinoma of head and neck metastatic	Phase 3	BE	AstraZeneca PLC	02 Oct 2020
Squamous cell carcinoma of head and neck metastatic	Phase 3	CA	AstraZeneca PLC	02 Oct 2020
Squamous cell carcinoma of head and neck metastatic	Phase 3	NL	AstraZeneca PLC	02 Oct 2020
Squamous cell carcinoma of head and neck metastatic	Phase 3	GR	AstraZeneca PLC	02 Oct 2020
Squamous cell carcinoma of head and neck metastatic	Phase 3	-	AstraZeneca PLC	02 Oct 2020
Squamous Cell Carcinoma of Head and Neck	Preclinical	US	AstraZeneca PLC	02 Oct 2020

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02459301 (IND221, Pubmed) Manual	Phase 1	Neoplasms	58	IPH2201	(ptuyvntnhy) = uvbdzzrgps ouckuzhzvt (iqrzlitdhi ) View more	Positive	15 Oct 2019
NCT03088059 (UPSTREAM, Pubmed \| Eur J Cancer Care (Engl)) Manual	Phase 2	Squamous Cell Carcinoma of Head and Neck	26	Monalizumab	(rsjeuicqch) = aynonwcwpg jmziuhetmg (fjacedplwo ) View more	Negative	09 Oct 2021
NCT04590963 (INTERLINK-1, Corporate Publications) Manual	Phase 3	Recurrent Squamous Cell Carcinoma of the Head and Neck	600	Cetuximab+Monalizumab	(hurbwxwehs) = not reach yxckfirgqs (ctnamxnpec )	Negative	01 Aug 2022
				Cetuximab+Placebo
NCT02671435 (ASCO2018) Manual	Phase 1	Metastatic Microsatellite Stable Colorectal Carcinoma	55	monalizumab+durvalumab (escalation)	(qtdbmwfaat) = hphtfcretg mgeykcmnii (scwjktizic ) View more	Positive	01 Jun 2018
				monalizumab+durvalumab (MSS-CRC expansion)	(cutnwjgrlk) = izytxezled brbdpqcgbr (kvkoagbdgy ) View more
NCT02643550 (ESMO2018) Manual	Phase 2	Recurrent Squamous Cell Carcinoma of the Head and Neck First line \| Second line \| Third line	40	cetuximab+monalizumab	(khifjjcbtf) = khtvrkiwfy bdcjhsmfhg (rluswjwnfu ) View more	Positive	20 Oct 2018
NCT02671435 (ASCO_GI2020) Manual	Phase 1/2	Metastatic Microsatellite Stable Colorectal Carcinoma First line Microsatellite Stable (MSS)	35	bevacizumab+chemotherapy+monalizumab+durvalumab (DMCB)	(uhkljjeonf) = oexnwcbtki gaubvrrzuy (leeijslgbc ) View more	Positive	25 Jan 2020
				cetuximab+chemotherapy+monalizumab+durvalumab (DMCC)	(uhkljjeonf) = jbmcoxsokr gaubvrrzuy (leeijslgbc ) View more
NCT03822351 (COAST, ESMO2021) Manual	Phase 2	Non-small cell lung cancer stage IIIA	189	durvalumab	(ajalnvrbbv) = pgdyzgpjrt uszomewahp (wpiytvtwes, 15.5 - 37.5) View more	Positive	17 Sep 2021
				durvalumab+oleclumab	(ajalnvrbbv) = wlmtlfkcyq uszomewahp (wpiytvtwes, 26.1 - 51.8) View more
NCT03794544 (AACR2022) Manual	Phase 2	Non-Small Cell Lung Cancer Neoadjuvant	84	Durvalumab	(ajgydcholy) = rpdouyldxi qyhzmguqxb (subelzjrkw, 2.4 - 29.2) View more	Positive	15 Jun 2022
				Durvalumab+Oleclumab	(ajgydcholy) = acmpbpyxeo qyhzmguqxb (subelzjrkw, 5.4 - 41.9) View more
NCT02643550 (ASCO2020) Manual	Phase 2	Head and neck cancer metastatic	40	cetuximab+monalizumab	(tuakbqegag) = ltadfjxiex yzxzmehpez (pfcyijptmd, 11 - 35) View more	Positive	29 May 2020
NCT02643550 (ESMO_IO2021) Manual	Phase 2	Recurrent Squamous Cell Carcinoma of the Head and Neck First line	40	durvalumab+Monalizumab+cetuximab	(pzqiixoydf) = yevqroqpba leggyqswzu (kocsjlsjmd, 20 - 48) View more	Positive	09 Dec 2021

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