pivekimab sunirine (PVEK) / AbbVie - LARVOL DELTA

CADENZA: Study of IMGN632 in Patients With Untreated BPDCN and Relapsed/Refractory BPDCN (clinicaltrials.gov) - P1/2 | N=179 | Active, not recruiting | Sponsor: AbbVie | Trial completion date: Dec 2025 ➔ Dec 2026

Monotherapy • Trial completion date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • IL3RA

Preclinical Characterization of the Anti-Leukemia Activity of the CD123 Antibody-Drug Conjugate, Pivekimab Sunirine (IMGN632) (ASH 2024) - "Since the above data suggested that TP53 alterations impaired the ability of PVEK to induce cytotoxicity in acute myeloid and lymphoblastic leukemia cells, we used TP53wild-type EOL-1, MOLM-13, MV4; 11, REH, and RS4; 11 cells and deleted TP53 from bulk cells via CRISPR/Cas9 and then exposed these engineered cells to idasanutlin to enrich for the population of TP53KO cells. Important modulators for the drug's cytotoxic effects we identified include CD123 expression levels, TP53 alterations, and overexpression of anti-apoptotic BCL-2 family proteins but surprisingly not activity of ATP transporter proteins. The clinical relevance of these findings should be explored."

IO biomarker • Preclinical • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Breast Cancer • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • BCL2 • BCL2L1 • CD123 • IL3RA

IMGN632-0802: IMGN632 as Monotherapy or With Venetoclax and/or Azacitidine for Participants With CD123-Positive Acute Myeloid Leukemia (clinicaltrials.gov) - P1/2 | N=218 | Active, not recruiting | Sponsor: AbbVie | Trial completion date: Dec 2024 ➔ Apr 2026 | Trial primary completion date: Dec 2024 ➔ Apr 2026

Monotherapy • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • IL3RA

MODULE 5: Potential Role of Menin Inhibitors and Other Novel Agents in the Treatment of AML (ASH 2024) - "This program is supported by educational grants from AbbVie Inc, Astellas, and Daiichi Sankyo Inc.Mechanism of action of menin inhibitors and rationale for their activity in AML with KMT2 rearrangements and NPM1 mutations Pharmacologic similarities and differences among various menin inhibitors under investigation for AML, such as revumenib, ziftomenib and BMF-219 Early efficacy and safety data with novel menin inhibitors for R/R AML Design, eligibility criteria and available efficacy and safety findings from the pivotal Phase II AUGMENT-101 trial evaluating revumenib for patients with R/R leukemias; efficacy of revumenib for AML with a KMT2 rearrangement FDA breakthrough therapy designation of revumenib; potential role in clinical practice Rationale for targeting CD123 in AML; structural components and mechanism of action of the anti-CD123 antibody-drug conjugate pivekimab sunirine Available data with, ongoing evaluation of and potential clinical role of pivekimab..."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD123 • IL3RA • NPM1

Overcoming Tagraxofusp-Erzs Monotherapy Resistance in Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) in a Real-World Clinical Setting. (PubMed, J Immunother Precis Oncol) - "Currently, standard treatment strategies include clinical trials; chemotherapy regimens such as hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (HCVAD); and tagraxofusp-erzs (TAG, previously SL-401) which is the first-in-class targeted therapy against CD123...However, despite promising results, there are still patients who may be resistant to TAG monotherapy and/or who respond but eventually relapse. Herein, we discuss an important patient case of BPDCN treated with TAG and review BPDCN treatment strategies."

Journal • Monotherapy • Real-world • Real-world evidence • Hematological Disorders • Hematological Malignancies • Oncology • CD123 • IL3RA

CADENZA: Study of IMGN632 in Patients With Untreated BPDCN and Relapsed/Refractory BPDCN (clinicaltrials.gov) - P1/2 | N=179 | Active, not recruiting | Sponsor: ImmunoGen, Inc. | Trial primary completion date: Dec 2024 ➔ Sep 2023

Monotherapy • Trial primary completion date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • IL3RA

A PHASE 1B/2 STUDY OF PIVEKIMAB SUNIRINE (PVEK, IMGN632) IN COMBINATION WITH VENETOCLAX/AZACITIDINE FOR PATIENTS WITH NEWLY DIAGNOSED CD123-POSITIVE ACUTE MYELOID LEUKEMIA (EHA 2024) - P1/2 | "The PVEK+AZA+VEN triplet in pts with ND unfit AML is currently enrolling across sites in France, Germany, Italy,Spain, UK and USA. Clinical trial information: NCT04086264."

Clinical • Combination therapy • P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD123 • IL3RA

A phase 1b/2 study of pivekimab sunirine (PVEK, IMGN632) in combination with venetoclax/azacitidine for patients with newly diagnosed CD123-positive acute myeloid leukemia. (ASCO 2024) - P1/2 | "Key secondary objectives are safety and tolerability, pharmacokinetics and immunogenicity. The PVEK+AZA+VEN triplet in pts with ND unfit AML is currently enrolling across sites in France, Germany, Italy, Spain, UK and USA."

Clinical • Combination therapy • P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD123 • IL3RA

IMGN632-0802: IMGN632 as Monotherapy or With Venetoclax and/or Azacitidine for Participants With CD123-Positive Acute Myeloid Leukemia (clinicaltrials.gov) - P1/2 | N=218 | Active, not recruiting | Sponsor: ImmunoGen, Inc. | Recruiting ➔ Active, not recruiting | Phase classification: P1b/2 ➔ P1/2

Enrollment closed • Monotherapy • Phase classification • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • IL3RA

Pivekimab sunirine (IMGN632), a novel CD123-targeting antibody-drug conjugate, in relapsed or refractory acute myeloid leukaemia: a phase 1/2 study. (PubMed, Lancet Oncol) - P1/2 | "Pivekimab sunirine showed single-agent activity across multiple doses, with a recommended phase 2 dose of 0·045 mg/kg once every 3 weeks. These findings led to a phase 1b/2 study of pivekimab sunirine plus azacitidine and venetoclax in patients with CD123-positive acute myeloid leukaemia."

Journal • P1/2 data • P2 data • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Hepatology • Leukemia • Neutropenia • Oncology • CD123 • IL3RA

Breakthrough in Blastic Plasmacytoid Dendritic Cell Neoplasm Cancer Therapy Owing to Precision Targeting of CD123. (PubMed, Int J Mol Sci) - "Ongoing developments with SL-401, IMGN632, CD123 chimeric antigen receptor (CAR) T-cells, and bispecific antibodies (BsAb) show promising advancements. The exploration of combinations such as CD123-targeted immunotherapies with azacitidine and venetoclax is suggested to enhance antineoplastic responses and improve survival rates in BPDCN patients. In conclusion, this multifaceted approach offers hope for more effective and tailored therapeutic interventions against this challenging hematologic malignancy."

Journal • Review • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Oncology • Transplantation • CD123 • IL3RA

Pivekimab sunirine (PVEK), a CD123 antibody-drug conjugate, exerts profound activity in preclinical models of paediatric acute lymphoblastic leukaemia (NDLR 2024) - No abstract available

Preclinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • CD123 • IL3RA

AbbVie Completes Acquisition of ImmunoGen (PRNewswire) - "AbbVie...announced today that it has completed its acquisition of ImmunoGen...With the completion of the acquisition, ImmunoGen is now part of AbbVie...ELAHERE (mirvetuximab soravtansine-gynx) is the first and only antibody-drug conjugate (ADC) approved by the U.S. Food and Drug Administration (FDA) in ovarian cancer...ImmunoGen's investigational Phase 1 asset, IMGN-151, is a next-generation FRα ADC for ovarian cancer with the potential for expansion into other solid tumor indications...Pivekimab sunirine, currently in Phase 2, is an investigational anti-CD123 ADC targeting blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare blood cancer, which was granted FDA breakthrough therapy designation for the treatment of relapsed/refractory BPDCN....AbbVie has acquired all outstanding ImmunoGen common stock for $31.26 per share."

M&A • Gynecologic Cancers • Hematological Malignancies • Oncology • Ovarian Cancer • Solid Tumor

Pivekimab Sunirine (PVEK, IMGN632), a CD123-Targeting Antibody-Drug Conjugate, in Combination with Azacitidine and Venetoclax in Patients with Newly Diagnosed Acute Myeloid Leukemia (ASH 2023) - "Encouraging CCRMRD- rates were observed across cytogenetic/molecular subsets, and the majority of responding pts achieved early and deep remissions, which may translate to improved clinical outcomes. The regimen was well tolerated with no new safety signals, and the addition of PVEK to the AZA-VEN backbone did not appear to meaningfully prolong count recovery."

Clinical • Combination therapy • Acute Myelogenous Leukemia • Constipation • Febrile Neutropenia • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Hepatology • Neutropenia • Renal Disease • CD123 • FLT3 • IDH1 • IDH2 • IL3RA • NPM1

Single-Cell Genomics and Proteomics Reveals Venetoclax-Resistant Monocytic Differentiation of TP53 LOH Clones in TP53 Mutant AML (ASH 2023) - " Patients 1 and 3 received treatment with CD47AB (Magrolimab), 5'-Azacitidine (Aza), and Venetoclax (Ven); Patient 2 received IMGN632 (CD123-targeting ADC), Aza and Ven. Patient 4 received p97 Inhibitor CB-5339; Patient 5 received CD47 inhibitor (ALX148), Aza, Ven... This study establishes a genotype-phenotype connection through single-cell proteogenomic profiling of TP53-mutated AML, describing the clonal evolution and immunophenotypic dynamics during treatment while proposing a potential mechanism of resistance."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2L1 • CD123 • CD14 • CD33 • CD34 • CD36 • CD68 • CD8 • EIF4EBP1 • ETV6 • IDH1 • IL3RA • ITGAM • KIT • TP53

Venetoclax Synergizes with IMGN632, a Novel CD123-Targeting Antibody Conjugated to a DNA Alkylating Payload, By Suppressing DNA Damage Response and Potentiating Apoptosis in Acute Myeloid Leukemia in Vitro Models (ASH 2023) - P1/2, P1b/2 | "Importantly, we previously showed high synergy of IMGN632 combination with BCL-2 inhibitor venetoclax (VEN) and DNA hypomethylating azacytidine (AZA) in AML cell lines and xenograft models (ASH 2020, #617). Together, these results suggest that VEN, apart from its canonical inhibitory effect on anti-apoptotic BCL-2, exerts previously unrecognized ability to suppress DDR program in AML and augments activity of DNA damaging IMGN632. Failure of cells to sustain DDR in the presence of VEN constitutes a key aspect of high efficacy of IMGN/VEN/AZA combination in AML."

IO biomarker • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CASP3 • CD123 • CHEK1 • FLT3 • IL3RA • MCL1

Spatial Response to Pivekimab Sunirine (IMGN632) In Vivo in a BPDCN Model (ASH 2023) - "Standard of care treatments for BPDCN patients are intense chemotherapy or tagraxofusp (Elzonris®)...Pivekimab sunirine was granted orphan drug and Breakthrough Therapy designation and is currently being tested for the treatment of BPDCN patients as monotherapy and, as a triplet therapy in combination with azacitidine and venetoclax for the treatment of AML patients...Pivekimab sunirine is a potent ADC targeting CD123 and is highly efficacious against an aggressive BPDCN cell line model. This finding reinforces the importance of its use for the treatment of BPDCN patients."

Preclinical • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Oncology • CD123 • IL3RA

Combination Chemotherapy (FLAG-Ida) With Pivekimab Sunirine (PVEK [IMGN632]) for the Treatment of Newly Diagnosed Adverse Risk Acute Myeloid Leukemia and Other High-Grade Myeloid Neoplasms (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Fred Hutchinson Cancer Center | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • IL3RA

ImmunoGen Presents Findings from Newly Diagnosed Acute Myeloid Leukemia Cohorts in Phase 1b/2 Study of Pivekimab Sunirine in Combination with Azacitidine and Venetoclax at ASH (Businesswire) - P1/2 | N=292 | NCT04086264 | Sponsor: ImmunoGen, Inc. | "In the overall population, CCR rate was 68% (34/50), CR rate was 54% (27/50), and MRD negativity rate among evaluable patients achieving CCR was 76% (22/29). MRD was assessed centrally by flow cytometry with <0.1% considered negative. Response rates and MRD negativity were numerically comparable between cohorts 1 and 2, despite differences in the venetoclax schedule....Among all MRD negative patients, the median time to MRD negativity was 1.87 months (range: 0.79-5.16 months)....Although follow-up duration was short (median 5.2 months), landmark overall survival estimate at 6 months is 86%....The triplet displayed a manageable safety profile; no new safety signals were observed compared to previously reported data."

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

MEET THE EXPERT - BLASTIC PLASMACYTIC DENDRITIC CELL NEOPLASMS (SIE 2023) - "Monotherapy with Tagraxofusp (TAG) has notably improved the outcome of these patients with an overall response rate (ORR) of 90% and a median 2-year survival still not reached, particularly for responding patients addressed to allogeneic stem cell transplant (ASCT).7 Further anti-CD123 therapies (IMGN632) are under active development.8 Intensive chemotherapy, with or without ASCT, was largely employed before the advent of TAG, and still has a role in BPDCN treatment, alone or in combination. Conventional chemotherapy, both AML-like and ALL-like, has the further advantage of being adaptable in terms of dosage and schedule to unfit/older patients. In this session, the main diagnostic and prognostic criteria, along with current treatments, will be addressed highlighting certainties and unmet needs in the management of this poor-risk disease."

Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Myelomonocytic Leukemia • CNS Tumor • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Myelodysplastic Syndrome • Oncology • Transplantation • CD123 • CD4 • CLEC4C • IL3RA • NCAM1 • TCF4

Pivekimab sunirine: Patent expiry related to composition-of-matter in 2036 (Immunogen) - Corporate Presentation

Patent • Oncology

Combination Chemotherapy (FLAG-Ida) With Pivekimab Sunirine (PVEK [IMGN632]) for the Treatment of Newly Diagnosed Adverse Risk Acute Myeloid Leukemia and Other High-Grade Myeloid Neoplasms (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: Fred Hutchinson Cancer Center | Initiation date: Nov 2023 ➔ Feb 2024

Trial initiation date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • IL3RA

ImmunoGen Reports Recent Progress and Third Quarter 2023 Financial Results (Businesswire) - "ANTICIPATED UPCOMING EVENTS: Report data from the 802 trial, evaluating the pivekimab sunirine (pivekimab) triplet with Venclexta (venetoclax) and Vidaza (azacitidine) in frontline acute myeloid leukemia (AML) at the American Society of Hematology (ASH) Annual Meeting in December 2023; Report top-line data from the pivotal frontline de novo cohort in the Phase 2 CADENZA trial of pivekimab in blastic plasmacytoid dendritic cell neoplasm (BPDCN) in 2024; Provide an update on the IMGC936 non-small cell lung cancer (NSCLC) cohort following a prespecified interim analysis."

P1/2 data • P2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Exploring Pivekimab Sunirine (IMGN632): A Next- Generation ADC for CD123+ Hematologic Malignancies (ADC-USA 2023) - "Discussing the pre-clinical aspects of the CD123 target and the novel IGN payload; Levering a wide therapeutic window and favorable safety profile to address unmet need in hematologic malignancies; Exploring the pivotal development as a monotherapy in BPDCN; Outlining key combinations strategies in frontline and R/R AML"

Acute Myelogenous Leukemia • Hematological Malignancies • Oncology • CD123 • IL3RA

IMGN632 as Monotherapy or With Venetoclax and/or Azacitidine for Participants With CD123-Positive Acute Myeloid Leukemia (clinicaltrials.gov) - P1b/2 | N=292 | Recruiting | Sponsor: ImmunoGen, Inc. | Trial completion date: Jun 2024 ➔ Dec 2024 | Trial primary completion date: Jun 2024 ➔ Dec 2024

Monotherapy • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD123 • IL3RA