IPH6101 / Innate - LARVOL DELTA

ANTITUMOR CHARACTERIZATION OF IPH6501, A NOVEL IL2V-ARMED TETRASPECIFIC NK CELL ENGAGER TARGETING CD20 B CELLS, IN DLBCL AND FL PATIENT SAMPLES, AND IN PRECLINICAL COMBINATION WITH R-CHOP (EHA 2025) - P1/2 | "Yet, there remains an unmet medical need for patients ineligible, refractory to, or relapsing (R/R) from these therapies.Leveraging natural killer (NK) cells emerges as a promising strategy in hematological malignancies, as reported in a Phase 1/2 study with IPH6101/SAR'579 in R/R AML (Garciaz, EHA 2024). The ex vivo preclinical evaluation of IPH6501 using patient samples provides supportive evidence to explore IPH6501 in R/R DLBCL and FL patients. Furthermore, the strong antitumor activity of IPH6501 in a rituximab-resistant model, together with the significant improvement of its antitumor activity when combined with R-CHOP in a rituximab sensitive model suggests that IPH6501 could be employed in B-NHL patients beyond monotherapy and paves the way for the evaluation of other combinations. IPH6501 is currently under investigation in a global first-in-human Phase 1/2 study (NCT06088654)."

IO biomarker • Preclinical • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • IL2

Innate Pharma Regains Its Rights on CD123 Targeting ANKET and Announces Sanofi’s Intention to Make a Strategic Investment in the Company (Businesswire) - "Innate Pharma SA...announce review of their January 2016 Research Collaboration and License Agreement (the '2016 Agreement') with Sanofi...As previously disclosed and in alignment with its current strategic priorities, Sanofi will opt to pursue the development of SAR’514/IPH6401 (BCMA ANKET) in autoimmune indications under the terms of the 2016 License Agreement; In alignment with both company's current strategic priorities, Sanofi and Innate agreed to terminate the 2016 Agreement as it relates to SAR’579/IPH6101 (CD123 ANKET); Innate will regain its rights on SAR’579/IPH6101 (CD123 ANKET)...The continued Sanofi-led Phase 1/2 study (clinical study identifier: NCT05839626) for the treatment of patients with relapsed or refractory multiple myeloma will be terminated early and SAR’514/IPH6401 will now be refocused to pursue development in autoimmune indications."

Licensing / partnership • Trial termination • Acute Myelogenous Leukemia • Multiple Myeloma

TCD17197: First-in-human Study of SAR443579 Infusion in Male and Female Children and Adult Participants With Relapsed or Refractory Acute Myeloid Leukemia (R/R AML), B-cell Acute Lymphoblastic Leukemia (B-ALL), High Risk-myelodysplasia (HR-MDS), or Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) (clinicaltrials.gov) - P1/2 | N=169 | Recruiting | Sponsor: Sanofi | Trial completion date: Oct 2030 ➔ May 2029 | Trial primary completion date: Dec 2025 ➔ Nov 2028

Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Juvenile Myelomonocytic Leukemia • Leukemia • Myelodysplastic Syndrome • Oncology • Pediatrics • IL3RA

Phase 1/2, Open-Label, Multi-Center Study Assessing the Safety, Tolerability and Preliminary Efficacy of CD123 Natural Killer Cell Engager (NKCE), SAR443579, in Combination with Venetoclax and Azacitidine in Patients with Newly Diagnosed Acute Myeloid Leukemia (AML) Who Are Ineligible for Intensive Chemotherapy (ASH 2024) - P1/2 | "The expected duration of this sub-study 1 is approximately 5 years with a follow-up period of 2 years post-treatment. The study is currently recruiting."

Clinical • Combination therapy • P1/2 data • Acute Myelogenous Leukemia • Acute Promyelocytic Leukemia • Cardiovascular • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • CD123 • FCGR3A • IL3RA

Innate Pharma Highlights Abstracts Selected for the ASH Annual Meeting 2024 (Businesswire) - "Innate Pharma SA...today announced that abstracts related to lacutamab health-related quality of life and translational data from the TELLOMAK trial and SAR443579, Sanofi-partnered ANKET® asset, have been selected for the American Society of hematology (ASH) Annual Meeting."

Clinical data • P2 data • Mycosis Fungoides • Sezary Syndrome • T Cell Non-Hodgkin Lymphoma

A Study to Investigate Natural Killer Cell Engager (SAR443579) With Different Agents in Participants With Hematological Malignancies (clinicaltrials.gov) - P1/2 | N=18 | Recruiting | Sponsor: Sanofi | Trial completion date: Feb 2029 ➔ Aug 2029

Trial completion date • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology

Preclinical characterization of IPH6501: a novel IL2v-armed tetraspecific NK cell engager targeting CD20 in relapsed or refractory B cell non-Hodgkin lymphoma subtypes and post-CAR-T therapy (SITC 2024) - P1/2 | "NK cell engager molecules have shown efficacy in acute myeloid lymphoma (IPH6101/SAR'579, NCT05086315)...In vitro, cytotoxicity assays reveal that IPH6501 stimulates PBMCs from post rituximab R/R B-NHL patients to kill a CD20+ lymphoma cell line...Cell collection were obtained through the CeVi_Collection Project from the CALYM Carnot Institute funded by the French National Research Council (ANR). Additional amples were collected and stored within the biobank of the CRB SUD, CRB HCL (BB-0033-00046), the CRB-Santé Rennes (BB-0033-00056), the CRB Cancer IUCTO (BB-0033-00014), the CRB CHU de Montpellier (BB-0033-00031) and CRB Gustave Roussy (2022- A00472-41) which has been declared to the Ministry of Higher Education and Research after receiving approval from the ethical committee."

IO biomarker • Preclinical • Acute Myelogenous Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • IL2RA

TCD17197: First-in-human Study of SAR443579 Infusion in Male and Female Children and Adult Participants With Relapsed or Refractory Acute Myeloid Leukemia (R/R AML), B-cell Acute Lymphoblastic Leukemia (B-ALL), High Risk-myelodysplasia (HR-MDS), or Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) (clinicaltrials.gov) - P1/2 | N=169 | Recruiting | Sponsor: Sanofi | N=126 ➔ 169 | Trial completion date: Nov 2026 ➔ Oct 2030

Enrollment change • Trial completion date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Juvenile Myelomonocytic Leukemia • Leukemia • Myelodysplastic Syndrome • Oncology • Pediatrics • IL3RA

Innate Pharma Reports First Half 2024 Business Update and Financial Results (Businesswire) - "In July 2024, Sanofi initiated a new Phase 1 / Phase 2, randomized, open label, multi-cohort, multi-center study (NCT06508489) assessing the safety, tolerability and preliminary efficacy of SAR’579 / IPH6101 administered in combination with azacitidine and venetoclax in patients with CD123 expressing hematological malignancies in newly diagnosed AML...IPH45 continues towards a Phase 1 trial in 2024...The investigator-sponsored CHANCES Phase 1 trial of IPH5301 with Institut Paoli-Calmettes is ongoing. Preliminary results will be presented at the upcoming (European Society of Medical Oncology) ESMO Annual Meeting 2024."

New P1 trial • P1 data • Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

A Study to Investigate Natural Killer Cell Engager (SAR443579) With Different Agents in Participants With Hematological Malignancies (clinicaltrials.gov) - P1/2 | N=18 | Recruiting | Sponsor: Sanofi

New P1/2 trial • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology

COMPLETED DOSE ESCALATION FROM THE FIRST-IN-HUMAN, PHASE 1/2 STUDY OF CD123 NK CELL ENGAGER, SAR443579, IN RELAPSED OR REFRACTORY ACUTE MYELOID LEUKEMIA OR HIGH RISK-MYELODYSPLASIA (EHA 2024) - P1/2 | "1%) with** prior exposure to venetoclax. SAR'579 was well tolerated up to doses of 6 mg/kg QW with observed clinical benefit in adult pts with R/R AMLand a maximum response rate seen at a target dose of 1 mg/kg (33% CR/CRi). The bell-shaped dose-responsecurve is also observed in vitro in AML cell models. SAR'579 received breakthrough designation by the US FDAand these data will form the basis for selection of recommended doses for development in the phase 2 portionof TCD17197."

P1/2 data • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • CD123 • IDH2 • IL3RA • NRAS • RUNX1 • TET2 • TP53

PRECLINICAL ASSESSMENT OF IPH6501, A FIRST-IN-CLASS IL2V-ARMED TETRASPECIFIC NK CELL ENGAGER DIRECTED AGAINST CD20 FOR R/R B-NHL, IN COMPARISON WITH A CD20-TARGETING T CELL ENGAGER (EHA 2024) - "Leveraging natural killer ( NK ) cells emerges as a promising strategy in hematological malignancies, as reported in a Phase 1 study with IPH6101/SAR ' 579 in R/R AML ( Stein, ASCO 2023; Bajel, ASH 2023 ) . The preclinical demonstrations of IPH6501 activities across various in vivo models and its effectiveness in ex vivo assays using cells from R/R B-NHL patients provide compelling evidence of its therapeutic potential and tolerability. IPH6501 is emerging as a promising new candidate within the treatment landscape for R/R B-NHL and is currently being investigated in a global, first-in-human phase 1/2 study ( NCT 06088654 ) ."

IO biomarker • Preclinical • Hematological Disorders • Non-Hodgkin’s Lymphoma • CD20 • FCGR3A • IL2RA • NKG2D

A PHASE 1/2 TRIAL INVESTIGATING SAFETY, TOLERABILITY, AND PRELIMINARY ANTITUMOR ACTIVITY OF IPH6501, A FIRST-IN-CLASS NK CELL ENGAGER, IN PATIENTS WITH R/R CD20-EXPRESSING NHL (EHA 2024) - P1/2 | "Leveraging natural killer (NK) cellsemerges as a promising strategy, as demonstrated in a Phase 1 study with IPH6101/SAR'579 in R/R AML (Stein,ASCO 2023; Bajel, ASH 2023), and offers a novel approach that could complement or provide an alternative toT-cell therapies. Not applicable. Trial in progress."

Clinical • IO biomarker • P1/2 data • Bone Marrow Transplantation • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation • CD20 • FCGR3A • IL2RA

EXPLORING DOSE-RESPONSE RELATIONSHIP OF A NOVEL CD123 NK CELL ENGAGER SAR443579 IN ACUTE MYELOID LEUKEMIA (AML) MODELS (EHA 2024) - P1/2 | "SAR'579 demonstrates potent anti-tumor activity against AML tumor cells expressing low, medium or highCD123 antigen densities, with a bell-shaped dose-response up to high concentrations in vitro, regardless ofCD123 receptor density or E:T ratio. A similar bell-shaped dose-effect was observed in vivo in mice, as alreadydescribed for some other immune cell engagers. Figure:Cytotoxicity against MOLM-13 AML cells."

Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Acute Lymphoblastic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CD123 • FCGR3A • IL3RA

Innate Pharma Shares Updated Results From the Sanofi Developed Blood Cancer Phase 1/2 SAR443579/IPH6101 Trial (Businesswire) - P1/2 | N=126 | NCT05086315 | Sponsor: Sanofi | "Innate Pharma SA...announced today that updated efficacy and safety results from the dose-escalation part of the Phase 1/2 study with SAR443579/IPH6101 (SAR'579)...were shared in an oral presentation at the European Hematology Association 2024 Congress in Madrid, Spain on Sunday, June 16 at 11:45 CEST...A maximum response rate was observed at a final target dose of 1 mg/kg every week with 5 AML patients achieving a CR (4 CR/1 CRi). The median treatment duration was 7.9 weeks, with durable CR (>10 months) observed in 3 patients with 2 remaining on maintenance therapy as of the data cutoff. SAR’579 was well tolerated up to doses of 6 mg/kg every week."

P1/2 data • Acute Myelogenous Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

Preclinical assessment of IPH6501, a first-in-class IL2v-armed tetraspecific NK cell engager directed against CD20 for R/R B-NHL, in comparison with a CD20-targeting T cell engager. (ASCO 2024) - "Leveraging natural killer (NK) cells emerges as a promising strategy in hematological malignancies, as shown in a Phase 1 study with IPH6101/SAR'579 in R/R AML (Stein, ASCO 2023; Bajel, ASH 2023). The preclinical demonstrations of IPH6501 activities across various in vivo models and its effectiveness in ex vivo assays using cells from R/R B-NHL patients provide compelling evidence of its therapeutic potential and tolerability. IPH6501 is emerging as a promising new candidate within the treatment landscape for R/R B-NHL and is currently being investigated in a global, first-in-human phase 1/2 study (NCT 06088654)."

IO biomarker • Preclinical • Hematological Disorders • Non-Hodgkin’s Lymphoma • CD20 • FCGR3A • IL2 • IL2RA • NKG2D

A phase 1/2, open-label, multicenter trial investigating the safety, tolerability, and preliminary antineoplastic activity of IPH6501, a first-in-class NK cell engager, in patients with relapsed and/or refractory CD20-expressing non-Hodgkin lymphoma. (ASCO 2024) - P1/2 | "Leveraging natural killer (NK) cells emerges as a promising strategy, as demonstrated in a Phase 1 study with IPH6101/SAR'579 in R/R AML (Stein, ASCO 2023; Bajel, ASH 2023), and offers a novel approach that could complement or provide an alternative to T-cell therapies. The Phase 2 part will enroll one or more cohorts of selected B-cell NHL subtypes to be determined at a later stage. Up to 184 subjects will be enrolled, and the study is open in the United States, Australia and Europe."

Clinical • IO biomarker • P1/2 data • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20 • FCGR3A • IL2 • IL2RA

Innate Pharma: Clarification Regarding SAR443579 Designation (Businesswire) - "Innate Pharma SA...today announced that in an abstract published on 14 May 2024 for the European Hematology Association 2024 Congress on SAR443579/IPH6101, submitted by Sanofi, it was mentioned that the molecule received breakthrough designation. This is an error. The molecule has US FDA Fast Track Designation, as communicated before in June 2023."

Commercial • Hematological Malignancies • Oncology

Innate Pharma Highlights Abstracts Selected for EHA 2024 Congress (Businesswire) - "Innate Pharma SA...announced today that four abstracts with Innate’s drug candidates have been accepted for the European Association of Hematology (EHA) 2024 Congress, taking place June 13-16, 2024 in Madrid, Spain. Two abstracts are related to SAR443579 (IPH6101), an investigational trifunctional anti-CD123 NKp46xCD16 NK cell engager from a joint research collaboration between Innate Pharma and Sanofi and currently being evaluated as a monotherapy in a Sanofi-sponsored Phase 1/2 clinical trial for the treatment of blood cancers with high unmet needs. Two abstracts are related to IPH6501, Innate’s second generation ANKET for the treatment of relapsed or refractory CD20-expressing B-cell Non-Hodgkin's Lymphoma, currently in Phase 1/2 clinical trial."

P1/2 data • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma • Oncology

Novel approaches for diagnosis & treatment of acute lymphoblastic and myeloid leukemia (ICKSH 2024) - "For BCP-ALL, this mainly concerns the introduction of blinatumomab and inotuzumab ozogamicin, as well as the recently developed menin inhibitor revumenib, which is mainly be of relevance for KMT2A-rearranged (infant) ALL. Other menin inhibitors are also under development, such as ziftomenib and JNJ-75276617. Other targeted therapy options are mainly relevant in Philadelphia-chromosome positive leukemias, and in adult ALL the concept of che- mo-free induction therapy is already under development consisting of combinations of tyrosine kinase inhibitors (TKIs) such as imatinib, da- satinib or ponatinib, in combination with with steroids or blinatumomab, and challenging the need for SCT in this disease...Also for T-cell ALL, newer therapy options are available including CAR T-cell therapy, for example the allogenic off-the-shelf, fractricide-resistant CD7-targeted CAR-T cell therapy studies in the WU-CART-007 study. For AML, immunotherapy is less well advanced, but next to..."

Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Ovarian Cancer • Pediatrics • Solid Tumor • CBFA2T3 • CD123 • CD7 • FLT3 • GLIS2 • IL3RA • KMT2A • NUP98

Innate Pharma Announces Advancement of Sanofi-developed NK Cell Engager SAR443579 / IPH6101 Progressing to Phase 2 for Blood Cancer Patients (Businesswire) - "Innate Pharma SA...announced that the first patient was dosed in the Phase 2 dose expansion part of the Sanofi-sponsored clinical trial of SAR443579 / IPH6101 (NCT05086315), evaluating SAR443579 as a monotherapy for the treatment of blood cancers with high unmet needs, including relapsed or refractory acute myeloid leukemia (R/R AML), B-cell acute lymphoblastic leukemia and high-risk myelodysplasia....Dosing of the first patient in the dose expansion part of the trial triggers a €4m milestone payment to Innate."

Financing • Trial status • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Myelodysplastic Syndrome

First-in-Human Study of the CD123 NK Cell Engager SAR443579 in Relapsed or Refractory Acute Myeloid Leukemia, B-Cell Acute Lymphoblastic Leukemia or High Risk-Myelodysplasia: Updated Safety, Efficacy, Pharmacokinetics and Pharmacodynamics (ASH 2023) - P1/2 | "Pts had received a median of 2.0 (1.0 –10.0) prior lines of treatment with 13 pts (30.2%) reporting prior hematopoietic stem cell transplantation and 36 pts (83.7%) with prior exposure to venetoclax. SAR'579 was well tolerated up to doses of 6000 µg/kg QW with observed clinical benefit in pts with R/R AML. The results are consistent with the predicted favorable safety profile."

Clinical • P1 data • PK/PD data • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Transplantation • CD123 • IL3RA

Innate Pharma Shares Efficacy and Safety Phase 1 /2 Results of NK Cell Engager SAR443579 / IPH6101 Developed by Sanofi at ASH 2023 (Businesswire) - P1/2 | N=126 | NCT05086315 | Sponsor: Sanofi | "Innate Pharma SA...announced today that the updated efficacy and safety results from an open-label, first-in-human, Phase 1/2 dose-escalation study of SAR443579 / IPH6101, an investigational CD123 targeting NKp46/CD16-based Natural Killer Cell Engager (NKCE) from a joint research collaboration between Innate Pharma and Sanofi were shared in a poster presentation at the American Society of Hematology 2023 Annual Meeting in San Diego, California....At the highest dose of 1000 μg/kg QW, 5/15 (33.3%) patients with AML achieved a CR (4 CR / 1 CRi)1. SAR443579 was well tolerated up to 6000 μg/kg QW with observed clinical benefit in patients with R/R AML, in line with the predicted favorable safety profile."

P1/2 data • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Effects of SAR443579, a trifunctional anti-CD123 NK cell engager (NKCE), on natural killer (NK) cell subsets at the single cell level (SITC 2023) - "6 Finally, we confirmed our findings at the protein level using flow cytometry and Meso-Scale Discovery (MSD) analyses. Conclusions Together, our work characterized peripheral blood NK cell compartments and explained the NK changes induced by SAR443579 in the presence of target cells at Single-Cell RNA and protein levels."

Oncology • CD123 • FCGR3A • IL3RA

A noval mouse model for preclinical efficacy of the antibodies associated with the target CD16A (SITC 2023) - "Background FDA has granted Fast Track Designation for SAR’579/IPH6101, a trifunctional anti-CD123 NKp46×CD16 NK cell engager, for the treatment of hematological malignancies...They have been utilized to study antibody therapies, immune cell-mediated cytotoxicity, and the efficacy and safety of therapeutic antibodies. These models provide valuable insights into FcγR biology and help guide the development of immunotherapies targeting FcγR-mediated pathways in human diseases."

Preclinical • Hematological Malignancies • Oncology • CD123 • FCGR2A • FCGR2B • FCGR3A • IL3RA