surzetoclax (ABBV-453) / AbbVie - LARVOL DELTA

Surzetoclax: A Potentially Best-In-Class BCL-2 Inhibitor for the Treatment of Multiple Myeloma with T(11;14) Translocation or High BCL-2 Expression (IMS 2026) - P1/2 | "TGI of the RS4;11 model was superior to that achieved with clinically relevant BCL-2 inhibitors venetoclax, sonrotoclax or lisaftoclax at equivalent doses and schedules...Importantly, surzetoclax combined effectively with daratumumab and dexamethasone in the KMS-27 and the BCL-2 high RPMI-8226 MM xenograft models. These data identify surzetoclax as a potential best-in-class, next-generation BCL-2 inhibitor that is in a phase-1/-2 clinical trial for the treatment of patients with R/R MM (ClinicalTrials.gov ID: NCT06953960)."

IO biomarker • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Small Lymphocytic Lymphoma • ANXA5 • BCL2L1 • BCL2L2 • MCL1

Phase 1/2, Open-Label, Platform Study of Surzetoclax with Etentamig in Biomarker-Selected Patients with Relapsed/Refractory Multiple Myeloma (RRMM) (IMS 2026) - P1/2 | "Venetoclax, a first-in-class BCL2 inhibitor (BCL2i), has shown efficacy in RRMM. N/A"

Biomarker • Clinical • IO biomarker • P1/2 data • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma

Surzetoclax (ABBV-453) in combination with daratumumab and dexamethasone in biomarker-selected patients with Relapsed/Refractory multiple myeloma: A Phase 1/2, multicenter, open-label platform study (ASH 2025) - P1/2 | "Venetoclax, a selective BCL2i, has shown efficacy in relapsed/refractory MM (RRMM) whencombined with Dara plus dexamethasone (Dex)...During dose escalation, surzetoclax will be administered orally (PO) in combination withsubcutaneous Dara and Dex PO.During the dose expansion and selection phase, 2 doses of surzetoclax plus Dara+Dex will beinvestigated in separate cohorts, with a comparator cohort of pomalidomide plus Dara+Dex...The trial in progress reported herein reflects advances in novel therapies for RRMM, providinggreater insight on surzetoclax and its potential to address key unmet needs for t(11; 14)-positive and/orBCL2high pts with MM. Enrollment is ongoing at active sites in the United States, Australia, and Israel."

Biomarker • Clinical • Combination therapy • IO biomarker • P1/2 data • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • BCL2L1

A Study to Assess Adverse Events and Change in Disease Activity of Oral Surzetoclax Alone or in Combination With Subcutaneous and/or Oral Antimyeloma Agents in Adult Participants With Multiple Myeloma (MM) (clinicaltrials.gov) - P1/2 | N=325 | Recruiting | Sponsor: AbbVie | N=199 ➔ 325

Adverse events • Enrollment change • Monotherapy • B Cell Lymphoma • Hematological Malignancies • Multiple Myeloma • Oncology

AbbVie to Present Phase 3 Etentamig Results and Data from Broad Multiple Myeloma Portfolio at the 2026 International Myeloma Society (IMS) Meeting (PRNewswire) - "Plenary presentation will feature Phase 3 CERVINO results demonstrating that etentamig met the study's dual primary endpoints of objective response rate (ORR) and progression-free survival (PFS) in relapsed/refractory multiple myeloma (RRMM); Additional presentations highlight research across the breadth of AbbVie's multiple myeloma portfolio, including ABBV-2001 (ISB 2001), a trispecific T-cell engager and surzetoclax, a BCL-2 inhibitor, and combination approaches....Additional presentations from these investigational assets will explore treatment sequencing, infection-related healthcare utilization and costs, and real-world outcomes, reinforcing AbbVie's strategy to advance understanding of disease heterogeneity, mechanisms of resistance and the evolving needs of patients living with multiple myeloma."

Clinical data • P1/2 data • P3 data • Multiple Myeloma

A Study to Assess Adverse Events and Change in Disease Activity of Oral Surzetoclax Alone or in Combination With Subcutaneous and/or Oral Antimyeloma Agents in Adult Participants With Multiple Myeloma (MM) (clinicaltrials.gov) - P1/2 | N=199 | Recruiting | Sponsor: AbbVie | N=130 ➔ 199

Adverse events • Enrollment change • Monotherapy • B Cell Lymphoma • Hematological Malignancies • Multiple Myeloma • Oncology • BCL2

BGB-21447, a next-generation Bcl-2 inhibitor, demonstrates superior potency and overcomes Venetoclax resistance in preclinical models of hematologic malignancies (AACR 2026) - P1 | "At 1.5 mg/kg, BGB-21447 showed superior antitumor efficacy compared to VEN at 15 mg/kg and ABBV-453 (AbbVie's selective Bcl-2 inhibitor) at 1.5 mg/mL. No significant weight loss or laboratory toxicities were observed.In conclusion, BGB-21447 surpasses VEN in potency and mutant coverage, and durably inhibits VEN-resistant tumors at well-tolerated doses in preclinical models. These findings support the ongoing Phase 1 clinical trials (NCT05828589, NCT06756932) evaluating BGB-21447 in B-cell malignancies and metastatic breast cancer."

IO biomarker • Preclinical • Breast Cancer • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • ANXA5 • BCL2A1 • BCL2L1 • BCL2L2 • CASP3 • CASP7 • MCL1

M25-275: A Study to Assess Adverse Events and Change in Disease Activity of Oral ABBV-453 Alone or in Combination With Subcutaneous and/or Oral Antimyeloma Agents in Adult Participants With Multiple Myeloma (MM) (clinicaltrialsregister.eu) - P1/2 | N=76 | Recruiting | Sponsor: AbbVie Deutschland GmbH & Co. KG

Adverse events • Monotherapy • New P1/2 trial • B Cell Lymphoma • Hematological Malignancies • Multiple Myeloma • Oncology

A Study Assessing Adverse Event and How Oral ABBV-453 Moves Through the Body in Adult Participants With Relapsed or Refractory (R/R) Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) (clinicaltrials.gov) - P1 | N=4 | Active, not recruiting | Sponsor: AbbVie | Trial completion date: Jul 2029 ➔ Jul 2027 | Trial primary completion date: Jul 2029 ➔ Jul 2027

Adverse events • Trial completion date • Trial primary completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

Abbv-453: A Highly Potent and Selective Next Generation Small Molecule Inhibitor of BCL-2 (ASH 2024) - P1 | "ABBV-453 demonstrated superior growth inhibition of the RS4; 11 xenograft compared to both sonrotoclax or lisaftoclax at equivalent doses and schedule. ABBV-453 has the potential to be the best-in-class next-generation BCL-2 inhibitor and is actively being investigated in phase 1 clinical trials in relapsed or refractory (R/R) MM (ClinicalTrials.gov ID, NCT05308654) and R/R CLL/SLL (NCT06291220)."

Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • ANXA5 • BCL2 • BCL2L1 • BCL2L2 • CASP3 • CASP7 • MCL1

A Study to Assess Adverse Events and Change in Disease Activity of Oral ABBV-453 Alone or in Combination With Subcutaneous and/or Oral Antimyeloma Agents in Adult Participants With Multiple Myeloma (MM) (clinicaltrials.gov) - P1/2 | N=130 | Recruiting | Sponsor: AbbVie | Not yet recruiting ➔ Recruiting

Adverse events • Enrollment open • Monotherapy • Hematological Malignancies • Multiple Myeloma • Oncology

Surzetoclax ABBV-453: Phase 1 Dose Escalation Study of Next-Generation BCL-2 Inhibitor in Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma (ICML 2025) - No abstract available

P1 data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

A Study Assessing Adverse Event and How Oral ABBV-453 Moves Through the Body in Adult Participants With Relapsed or Refractory (R/R) Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) (clinicaltrials.gov) - P1 | N=4 | Active, not recruiting | Sponsor: AbbVie | Recruiting ➔ Active, not recruiting | N=80 ➔ 4

Adverse events • Enrollment change • Enrollment closed • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

A Study to Assess Adverse Events and Change in Disease Activity of Oral ABBV-453 Alone or in Combination With Subcutaneous and/or Oral Antimyeloma Agents in Adult Participants With Multiple Myeloma (MM) (clinicaltrials.gov) - P1/2 | N=130 | Not yet recruiting | Sponsor: AbbVie

Adverse events • Monotherapy • New P1/2 trial • Hematological Malignancies • Multiple Myeloma • Oncology

A Study Assessing Adverse Event and How Oral ABBV-453 Moves Through the Body in Adult Participants With Relapsed or Refractory (R/R) Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) (clinicaltrials.gov) - P1 | N=80 | Recruiting | Sponsor: AbbVie | Initiation date: Aug 2024 ➔ Jan 2025

Adverse events • Trial initiation date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

A Study to Assess the Adverse Events and Change in Disease Activity in Adult Participants With Relapsed or Refractory Multiple Myeloma Receiving Oral ABBV-453 Tablets (clinicaltrials.gov) - P1 | N=34 | Active, not recruiting | Sponsor: AbbVie | Recruiting ➔ Active, not recruiting | N=360 ➔ 34 | Trial completion date: Aug 2026 ➔ Dec 2025 | Trial primary completion date: Aug 2026 ➔ Feb 2024

Adverse events • Biomarker • Enrollment change • Enrollment closed • IO biomarker • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology • BCL2

A Study Assessing Adverse Event and How Oral ABBV-453 Moves Through the Body in Adult Participants With Relapsed or Refractory (R/R) Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) (clinicaltrials.gov) - P1 | N=80 | Recruiting | Sponsor: AbbVie | Not yet recruiting ➔ Recruiting

Adverse events • Enrollment open • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

A Study Assessing Adverse Event and How Oral ABBV-453 Moves Through the Body in Adult Participants With Relapsed or Refractory (R/R) Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) (clinicaltrials.gov) - P1 | N=80 | Not yet recruiting | Sponsor: AbbVie

Adverse events • New P1 trial • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

A Study to Assess the Adverse Events and Change in Disease Activity in Adult Participants With Relapsed or Refractory Multiple Myeloma Receiving Oral ABBV-453 Tablets (clinicaltrials.gov) - P1 | N=360 | Recruiting | Sponsor: AbbVie | Trial completion date: Apr 2026 ➔ Aug 2026 | Trial primary completion date: Apr 2026 ➔ Aug 2026

Adverse events • Biomarker • IO biomarker • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology • BCL2

A Study to Assess the Adverse Events and Change in Disease Activity in Adult Participants With Relapsed or Refractory Multiple Myeloma Receiving Oral ABBV-453 Tablets (clinicaltrials.gov) - P1 | N=360 | Recruiting | Sponsor: AbbVie | N=48 ➔ 360

Adverse events • Biomarker • Enrollment change • IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • BCL2

A Study to Assess the Adverse Events and Change in Disease Activity in Adult Participants With Relapsed or Refractory Multiple Myeloma Receiving Oral ABBV-453 Tablets (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: AbbVie | N=21 ➔ 48

Adverse events • Biomarker • Enrollment change • IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • BCL2

A Study to Assess the Adverse Events and Change in Disease Activity in Adult Participants With Relapsed or Refractory Multiple Myeloma Receiving Oral ABBV-453 Tablets (clinicaltrials.gov) - P1 | N=21 | Recruiting | Sponsor: AbbVie | Trial primary completion date: Aug 2025 ➔ Apr 2026

Adverse events • Biomarker • IO biomarker • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology • BCL2

New Funding Awards September 2022 (Duke University School of Medicine) - ""Robert Tighe of Pulmonary has received an award (1R01-ES034350-01) from the National Institutes of Health for a project entitled 'R01_Monocyte-derived alveolar macrophage drives inflammatory response to lung ozone exposure.' Total funding will be $3,002,300....Cristina Gasparetto of Cell Therapy has received an award from AbbVie Inc. for a project entitled 'First-in-Human Two-Part Study of the BCL-2 Inhibitor ABBV-453 in Biomarker-Selected Subjects with Relapsed or Refractory Multiple Myeloma.' Total funding will be $292,276."

Announcement

A Study to Assess the Adverse Events and Change in Disease Activity in Adult Participants With Relapsed or Refractory Multiple Myeloma Receiving Oral ABBV-453 Tablets (clinicaltrials.gov) - P1 | N=21 | Recruiting | Sponsor: AbbVie | Not yet recruiting ➔ Recruiting

Adverse events • Biomarker • Enrollment open • IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • BCL2

A Study to Assess the Adverse Events and Change in Disease Activity in Adult Participants With Relapsed or Refractory Multiple Myeloma Receiving Oral ABBV-453 Tablets (clinicaltrials.gov) - P1 | N=21 | Not yet recruiting | Sponsor: AbbVie

Adverse events • Biomarker • IO biomarker • New P1 trial • Hematological Malignancies • Multiple Myeloma • Oncology • BCL2