pivekimab sunirine (PVEK) / AbbVie - LARVOL DELTA

EFFICACY AND SAFETY OF PIVEKIMAB SUNIRINE (PVEK) IN PATIENTS (PTS) WITH BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM (BPDCN) IN THE CADENZA STUDY (EHA 2025) - P1/2 | "Pts with R/R BPDCN had received 1-3 prior systemic therapies; 57% had prior tagraxofusp (TAG). PVEK treatment demonstrated promising efficacy, with high and durable CR + CRc responses, and was tolerable at the RP2D. The safety profile was manageable, with no CLS events, predominantly low-grade peripheral edema, and very low incidence of resolvable VOD, a potential TEAE important to monitor during treatment. These results support PVEK as a potential new treatment option for adult pts with BPDCN."

Clinical • Fatigue • Hematological Malignancies • Hepatology • Oncology • CD123 • IL3RA

Efficacy and safety of pivekimab sunirine in blastic plasmacytoid dendritic cell neoplasm in patients with prior or concomitant hematologic malignancy: Results from the cadenza study (ASH 2025) - P1/2 | "For this population of pts with PCHM with complex disease management and limitedtreatment options, response rates and duration of response with PVEK treatment were similar to the denovo BPDCN population in the CADENZA study. Median OS in the overall 1L population was not impactedby pts with PCHM. Importantly, almost half of pts with PCHM transitioned to SCT, despite being older andmore frail, representing a potential breakthrough therapeutic option for this high-risk BPDCN ptsubgroup."

Clinical • Chronic Myelomonocytic Leukemia • CNS Disorders • Hematological Malignancies • Insomnia • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Sleep Disorder • CD123 • IL3RA

Pivekimab Sunirine in Blastic Plasmacytoid Dendritic Cell Neoplasm. (PubMed, J Clin Oncol) - P1/2 | "PVEK, with convenient dosing, led to high, durable responses, especially in frontline BPDCN, and a manageable safety profile."

Clinical • Journal • Fatigue • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Thrombocytopenia • Transplantation • CD123 • IL3RA

Efficacy and safety of pivekimab sunirine in combination with venetoclax plus azacitidine in unfit patients with newly diagnosed Acute Myeloid Leukemia (ASH 2025) - "Unfit pts with newly diagnosed CD123-postive AML demonstrated high CR rates withPVEK+VEN+AZA. These robust response rates were observed across the select mutational profiles tested.Follow up with duration of response and survival estimates among all pts, by molecular subgroups andMRD negativity status, are being evaluated. Triplet therapy in unfit 1L pts with CD-123–positive AML waswell-tolerated, and no new safety signals were observed."

Clinical • Combination therapy • Acute Myelogenous Leukemia • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myocardial Infarction • Neutropenia • Respiratory Diseases • Thrombocytopenia • CD123 • IL3RA

Efficacy and safety of pivekimab sunirine (PVEK) in patients (pts) with blastic plasmacytoid dendritic cell neoplasm (BPDCN) in the CADENZA study. (ASCO 2025) - P1/2 | "Pts with R/R BPDCN had received 1-3 prior systemic therapies; 57% had prior tagraxofusp. PVEK treatment demonstrated promising efficacy, with high and durable CR + CRc responses. PVEK was tolerable at the RP2D. The safety profile was manageable, with no CLS events."

Clinical • Hematological Malignancies • Hepatology • Oncology • CD123 • IL3RA

Pivekimab sunirine: Regulatory approval for BPDCN in 2026 (AbbVie) - Q4 2025 Results

Approval • Blastic Plasmacytoid Dendritic Cell Neoplasm • Hematological Malignancies • Oncology

Pivekimab sunirine in blastic plasmacytoid dendritic cell neoplasm: assessing spatial response and unraveling resistance mechanisms. (PubMed, Haematologica) - "Not available."

Journal • Oncology

A phase 1b/2 study of pivekimab sunirine (PVEK, IMGN632) in combination with venetoclax/azacitidine or magrolimab for patients with CD123-positive acute myeloid leukemia (AML). (ASCO 2023) - P1b/2 | "The PVEK+Magro doublet (Regimen E) is planned to be open for enrollment mid-2023 at sites in the USA. Clinical trial information: NCT04086264."

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

Broad Activity for the Pivekimab Sunirine (PVEK, IMGN632), Azacitidine, and Venetoclax Triplet in High-Risk Patients with Relapsed/Refractory Acute Myeloid Leukemia (AML) (ASH 2022) - P1b/2 | "With a manageable safety profile in patients with R/R AML, the higher-intensity cohorts of the novel PVEK triplet demonstrated anti-leukemia activity across several difficult-to-treat subsets of patients. Enrollment and follow-up in both relapsed and frontline patients are ongoing (NCT04086264). Additional and updated safety and efficacy data will be presented at ASH."

Clinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Transplantation • CD123 • FLT3

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

INTERIM ANALYSIS OF A REGISTRATION ENABLING STUDY OF PIVEKIMAB SUNIRINE (PVEK, IMGN632) A CD123-TARGETING ANTIBODY-DRUG CONJUGATE, IN PATIENTS WITH BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM (BPDCN) (EHA 2023) - P1/2 | "BPDCN currently has 1 approved therapy, tagraxofusp (TAG), with a median age of 68, CR/CRc rate of 57% and mOS of 15.8 mos (n=65; Pemmaraju JCO 2022). PVEK demonstrates compelling activity in frontline and R/R BPDCN pts, including durable responses in the R/R setting for pts who received prior TAG. PVEK safety was manageable with primarily low-grade IRRs and edema and no new safety signals were observed. Enrollment continues in the pivotal de novo frontline BPDCN cohort (NCT03386513) Antibody targeting, Monoclonal antibody, Myeloid malignancies"

Clinical • Chronic Myelomonocytic Leukemia • Constipation • Fatigue • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Neutropenia • Oncology • Thrombocytopenia • Transplantation • CD123

A Study to Assess Adverse Events and How Intravenous (IV) Pivekimab Sunirine Moves Through the Body in Pediatric Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML) (clinicaltrials.gov) - P1 | N=18 | Not yet recruiting | Sponsor: AbbVie

Adverse events • New P1 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics

Current status and future potential of CD123-based targeted therapies for acute leukemia. (PubMed, Expert Opin Biol Ther) - "It discusses completed and ongoing clinical trials for agents such as tagraxofusp, pivekimab sunirine, flotetuzumab, vibecotamab, and investigational CAR T-cell therapies (e.g. MB-102, UCART123v1.2). While clinical activity has been demonstrated, especially in BPDCN, therapeutic durability and safety remain hurdles. Precision in antigen targeting, combination strategies, and toxicity management will be critical for successful integration of CD123-directed therapies into standard clinical practice."

Journal • Review • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • CD123 • IL3RA

CD123-targeted radiotheranostics of Acute Myeloid Leukemia with 89Zr/177Lu-labeled pivekimab (ASH 2025) - "Pivekimabsunirine (IMGN632) is an antibody–drug conjugate (ADC) comprising a CD123-targeting antibodypivekimab (Pive) and indolinobenzodiazepine pseudodimers (IGNs), a DNA-interacting payload...Therewas an insignificant difference between high and low dose treatments (non-significant, p = 0.64).Conclusions We found CD123 was a good target for imaging and therapy of AML in a mouse model.[89Zr]Zr-DFO-Pive could capture all patients who may benefit from therapy targeting CD123 and monitorthe therapeutic effects in real-time. [177Lu]Lu-DTPA-Pive showed potent AML suppression and may be ofsignificant help in AML patient management."

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

Pivekimab sunirinine (PVEK) combined with FLAG-IDA for medically fit adults with untreated adverse-risk Acute Myeloid Leukemia (AML) or other high-grade myeloid neoplasms (NCT06034470) (ASH 2025) - P1 | "Pivekimab sunirine (PVEK,IMGN632) is a first-in-class antibody drug conjugate comprising a high-affinity CD123 antibody, cleavablelinker, and an indolinobenzodiazepine (IGN) payload. PVEK has shown anti-leukemia activity in earlyphase trials both as a single agent and in combination with azacitidine and venetoclax...Other chemotherapy included G-CSF (days 0-5),fludarabine (30 mg/m2 days 1-5), cytarabine 2 g/m2 (days 1-5) and idarubicin 10 mg/m2 (days 1-3)...Three doses of dexamethasone were administered prior to PVEK for infusion reactionprophylaxis... Addition of PVEK to FLAG-IDA was tolerable at all explored dose levels and resulted in highresponse rates in a population that is notoriously challenging to treat. Dose escalation is complete, andadditional recruitment to DL3 is ongoing to better estimate response and outcomes, with updated resultsto be presented at the meeting."

Clinical • Acute Myelogenous Leukemia • Febrile Neutropenia • Gastrointestinal Disorder • Hematological Malignancies • Infectious Disease • Leukemia • Respiratory Diseases • CD123 • FLT3 • IL3RA

PVEK (Antibody Drug Conjugate) in Newly Diagnosed AML (PRNewswire) - "PVEK is a first-in-class antibody-drug conjugate comprised of a high-affinity anti-CD123 antibody and an indolinobenzodiazepine pseudodimer (IGN) payload. An oral presentation will showcase data from the dose expansion part of an open-label Phase 1b/2 study of PVEK combined with venetoclax and azacitidine (VEN + AZA) in newly diagnosed, CD123-positive AML patients (n=49) who are unfit for intensive chemotherapy (NCT04086264). The results show high CR rates of 63.3% with PVEK+VEN+AZA. The most common TEAEs (any grade) were neutropenia and thrombocytopenia (both at 69%), constipation (61%) and peripheral edema (51%).5 These data highlight the need to further evaluate this regimen in a randomized trial."

P1/2 data • Acute Myelogenous Leukemia

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

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 • SCARB1 • 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 | "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 • Hematological Malignancies • Oncology • CD123 • 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

MODULE 2: Selection of Therapy for Younger Patients with AML without a Targetable Mutation; Promising Investigational Strategies (ASH 2025) - "This program is supported by educational grants from AbbVie Inc., Astellas, Daiichi Sankyo Inc., Kura Oncology, and Rigel Pharmaceuticals Inc.Outcomes observed with standard intensive chemotherapy regimens for younger patients with unfavorable prognostic features, such as complex karyotype and TP53 mutation Available findings with and ongoing investigation of venetoclax-based regimens for younger, fit patients with newly diagnosed AML; current role outside of a research setting Activity, tolerability and current role, if any, of venetoclax-based regimens for younger patients with relapsed/refractory (R/R) AML Rationale for targeting CD123 in AML; mechanism of action and structural components of pivekimab sunirine Early data with pivekimab sunirine as monotherapy and ongoing evaluation as a component of combination regimens Other promising investigational agents and strategies for patients with AML"

Clinical • Acute Myelogenous Leukemia • CD123 • IL3RA • TP53

AbbVie Submits Biologics License Application (BLA) to U.S. FDA for Pivekimab sunirine (PVEK) - an Investigational Antibody-Drug Conjugate (ADC) to Treat Rare Cancer with Limited Treatment Options (Businesswire) - "The submission is based on data from the Phase 1/2 CADENZA trial, a global study evaluating the safety and efficacy of PVEK in BPDCN."

FDA filing • Blastic Plasmacytoid Dendritic Cell Neoplasm

Efficacy and Safety of Pivekimab Sunirine (PVEK) in Patients With Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) in the CADENZA Study (SOHO 2025) - "Patients with R/R BPDCN had 1-3 prior systemic therapies; 57% had prior tagraxofusp. PVEK treatment demonstrated promising efficacy, with high and durable CR + CRc responses, and was tolerable at RP2D with a manageable safety profile and no CLS events. These results support PVEK as a potential treatment for adults with BPDCN. Previously presented at ASCO 2025."

Clinical • Oncology • CD123 • IL3RA