asaretoclax (ZN-d5) / Zentalis Pharma - LARVOL DELTA

ZN-d5-001: Phase 1 First in Human Study of ZN-d5 as a Single Agent (clinicaltrials.gov) - P1 | N=39 | Completed | Sponsor: K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc. | Recruiting ➔ Completed | N=115 ➔ 39 | Trial completion date: Jan 2025 ➔ Dec 2023 | Trial primary completion date: Aug 2024 ➔ Dec 2023

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2

ZN-d5-003: Phase 1/2 Study of ZN-d5 for the Treatment of Relapsed or Refractory Light Chain (AL) Amyloidosis (clinicaltrials.gov) - P1/2 | N=18 | Completed | Sponsor: K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc. | Active, not recruiting ➔ Completed | N=135 ➔ 18 | Trial completion date: Dec 2025 ➔ Feb 2024 | Trial primary completion date: May 2025 ➔ Feb 2024

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Amyloidosis

ZN-d5-004C: Study of the ZN-d5 and ZN-c3 in Subjects With Acute Myeloid Leukemia (AML) (clinicaltrials.gov) - P1/2 | N=40 | Terminated | Sponsor: K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc. | N=95 ➔ 40 | Trial completion date: Feb 2026 ➔ Jul 2024 | Recruiting ➔ Terminated | Trial primary completion date: Mar 2025 ➔ Jul 2024; Sponsor decision

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2

ZN-d5-002: A Food Effect Study of ZN-d5 in Healthy Female Volunteers (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc. | Not yet recruiting ➔ Completed

Trial completion

Zentalis Pharmaceuticals Reports Second Quarter 2024 Financial Results and Operational Progress (GlobeNewswire) - P1/2 | N=95 | NCT05682170 | Sponsor: K-Group Alpha, Inc. | "Today, Zentalis is disclosing that it is no longer developing the combination of its BCL-2 inhibitor, ZN-d5, with azenosertib, and is discontinuing development of ZN-d5.... Of the 6 patients who completed at least two cycles of therapy and underwent a cycle 3, day 1 bone marrow (BM) aspirate: 1 achieved a complete remission with incomplete hematologic recovery (CRi) and became transplant eligible, 2 patients had decreased BM blast counts, 2 had stable BM blasts, and 1 patient had increased BM blasts. The safety profile was manageable and in-line with other combinations in the R/R AML disease setting."

Discontinued • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Phase 1/2 Study of ZN-d5 for the Treatment of Relapsed or Refractory Light Chain (AL) Amyloidosis (clinicaltrials.gov) - P1/2 | N=135 | Active, not recruiting | Sponsor: K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Amyloidosis

Zentalis Pharmaceuticals Announces Pricing of Underwritten Offering of Common Stock (GlobeNewswire) - "Zentalis® Pharmaceuticals, Inc...announced the pricing of an underwritten offering of 11,032,656 shares of its common stock at an offering price of $22.66 per share, for total gross proceeds of approximately $250.0 million, before deducting underwriting discounts and commissions and offering expenses payable by the Company. All of the common stock is being offered by the Company. The offering is expected to close on June 20, 2023, subject to customary closing conditions. The Company intends to use the net proceeds from the offering to fund ongoing and planned clinical trials, and for working capital and other general corporate purposes. Based on these planned uses of proceeds, the Company believes that the net proceeds from the offering and its existing cash, cash equivalents and marketable securities will be sufficient to fund its operating expenses and capital expenditure requirements into 2026."

Financing • Acute Myelogenous Leukemia • Breast Cancer • Colorectal Cancer • Diffuse Large B Cell Lymphoma • Endometrial Cancer • Fallopian Tube Cancer • Follicular Lymphoma • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Hematological Malignancies • Leukemia • Lung Cancer • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Melanoma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Osteosarcoma • Ovarian Cancer • Pancreatic Adenocarcinoma • Pancreatic Cancer • Peripheral T-cell Lymphoma • Peritoneal Cancer • Sarcoma • Skin Cancer • Small Cell Lung Cancer • Solid Tumor • T Cell Non-Hodgkin Lymphoma • Thoracic Cancer • Triple Negative Breast Cancer • Urothelial Cancer • Uterine Cancer

A PHASE 1/2 MULTI-CENTER, DOSE-FINDING STUDY INVESTIGATING THE SAFETY, TOLERABILITY, PK AND EFFICACY OF ZN-D5, A NOVEL BCL-2 INHIBITOR, IN PATIENTS WITH RELAPSED/REFRACTORY AL AMYLOIDOSIS (EHA 2023) - P1/2 | "Recently, the addition of subcutaneous daratumumab to the standard first-line regimen of cyclophosphamide, bortezomib, and dexamethasone (CyBorD) was shown to significantly improve complete hematologic and organ response rates. This study will evaluate treatment of AL amyloidosis utilizing BCL-2 inhibition. Dose escalation cohorts arecurrently undergoing evaluation and the study is open to enrollment. Upon determination of the RP2D, the study will commence Phase 2."

Clinical • P1/2 data • Amyloidosis • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Rare Diseases

A phase 1/2 dose escalation study of the BCL-2 inhibitor ZN-d5 and the WEE1 inhibitor azenosertib (ZN-c3) in patients (Pts) with acute myeloid leukemia (AML). (ASCO 2023) - P1/2 | "For the dose-escalation azenosertib monotherapy (n≈15) and ZN-d5 combination (n≈40) cohorts, pts must have relapsed/refractory (R/R) disease after ≥1 line of AML therapy that may include the BCL-2 inhibitor, venetoclax. Pts will remain on study until disease progression, failure to respond, remission if additional therapy is clinically indicated, withdrawal of consent, loss to follow-up, or death. Clinical trial information: NCT05682170."

Clinical • IO biomarker • P1/2 data • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Oncology • TP53 • WEE1

A Phase I Study of ZN-d5 in Chinese Subjects With Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=8 | Terminated | Sponsor: Zentera Therapeutics HK Limited | N=30 ➔ 8 | Trial completion date: Mar 2024 ➔ May 2023 | Enrolling by invitation ➔ Terminated; Sponsor's decision

Enrollment change • Monotherapy • Trial completion date • Trial termination • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Zentalis Pharmaceuticals Reports First Quarter 2023 Financial Results and Operational Updates (GlobeNewswire) - "On track to announce monotherapy dose in first half 2023. The Company is optimizing monotherapy dosing across the azenosertib program with the goal of maximizing exposure and tolerability, as well as enabling the potential clinical benefits of the agent to reach the broadest range of patients. The Company remains on track to provide an update on azenosertib monotherapy dosing in the first half of 2023....Amyloidosis study. As previously communicated, Zentalis plans to announce interim clinical data and disclose the dose for the Phase 1/2 monotherapy clinical trial of ZN-d5 in relapsed or refractory light chain (AL) amyloidosis in the second half of 2023. AML study. The Company has initiated a Phase 1/2 combination study of ZN-d5 and azenosertib in relapsed or refractory acute myeloid leukemia (AML) and, as previously disclosed, expects to provide preliminary data from the trial in the second half of 2023."

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

Phase 1 First in Human Study of ZN-d5 as a Single Agent (clinicaltrials.gov) - P1 | N=115 | Recruiting | Sponsor: K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc. | N=85 ➔ 115 | Trial completion date: May 2023 ➔ Jan 2025 | Trial primary completion date: Oct 2022 ➔ Aug 2024

Enrollment change • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2

A Phase 1/2 Multi-Center, Dose-Finding Study to Assess Safety, Tolerability, PK and Efficacy of ZN-d5, a Novel BCL-2 Inhibitor, for Treatment of Subjects with Relapsed/Refractory AL Amyloidosis (ASH 2022) - P1/2 | "Recently, the addition of subcutaneous daratumumab to the standard CyBorD (cyclophosphamide, bortezomib, and dexamethasone) as first-line regimen, was shown to significantly improve complete hematologic and organ response rates. This study will evaluate treatment of AL amyloidosis utilizing BCL-2 inhibition and will test the hypothesis of whether t(11; 14) is a relevant predictive biomarker. Dose escalation cohorts are currently undergoing evaluation and the study is open to enrollment. Upon determination of a recommended phase 2 dose, the study will commence Phase 2."

Clinical • IO biomarker • P1/2 data • Amyloidosis • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Rare Diseases

Zentalis Pharmaceuticals Reports Full Year 2022 Financial Results and Operational Updates (GlobeNewswire) - "AML study. The Company has initiated a Phase 1/2 combination study of ZN-d5 and azenosertib in relapsed or refractory acute myeloid leukemia (AML) and expects to provide preliminary data from the trial in the second half of 2023."

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

Study of the ZN-d5 and ZN-c3 in Subjects With Acute Myeloid Leukemia (AML) (clinicaltrials.gov) - P1/2 | N=95 | Recruiting | Sponsor: K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.

New P1/2 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2

Zentalis Pharmaceuticals Reports Third Quarter 2022 Financial Results and Operational Updates (GlobeNewswire) - "The Company has generated preclinical data showing that Cyclin E overexpression sensitizes cancer cells to the anti-tumor effects of ZN-c3 as well as preliminary retrospective clinical data that Cyclin E protein levels may be associated with clinical benefit from ZN-c3. The Company plans to present the preclinical data in the first half of 2023....The Company will be presenting initial data from its Phase 1/2 combination trial of ZN-c3 and chemotherapy in osteosarcoma in a poster session at the upcoming Connective Tissue Oncology Society (CTOS) 2022 Annual Meeting, being held November 16-19 in Vancouver....Dosing with food is ongoing in patients in non-Hodgkin lymphoma (NHL) and amyloidosis, and the combination study of ZN-d5 and ZN-c3 in acute myeloid leukemia (AML) is scheduled to initiate in the fourth quarter of 2022."

New trial • P1 data • Preclinical • Trial status • Acute Myelogenous Leukemia • Gynecologic Cancers • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology • Osteosarcoma • Ovarian Cancer • Sarcoma • Solid Tumor

[VIRTUAL] A phase I dose-escalation study of ZN-d5, an BCL-2 inhibitor with improved selectivity, in patients with advanced non-Hodgkin lymphoma (NHL) or acute myeloid leukemia (AML) (ESMO 2021) - P1 | "ZN-d5 is a novel, oral, once-daily BH3 mimetic with improved selectivity for BCL-2 over BCL-xL compared to the commercially available BCL-2 inhibitor venetoclax, which could reduce the rate of thrombocytopenia. Clinical activity is assessed in the NHL disease cohort according to the 2014 Lugano classification and for AML according to the European LeukemiaNet 2017 recommendations. Subject recruitment is ongoing."

Clinical • IO biomarker • P1 data • Acute Myelogenous Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • BCL2L1

Zentalis Pharmaceuticals Announces $25 Million Equity Investment from Pfizer (GlobeNewswire) - "Zentalis intends to use the net proceeds of the offering to help fund ongoing and planned clinical trials, including studies of ZN-c3, its Wee1 inhibitor, and ZN-d5, its BCL-2 inhibitor, and for working capital and general corporate purposes. With prioritization of the clinical development of ZN-c3 and ZN-d5, budget reallocation and Pfizer’s investment, the Company extends current cash runway into Q1 2024."

Financing • Oncology

Combination of the BCL-2 inhibitor ZN-d5 with the WEE1 inhibitor ZN-c3 shows additive or synergistic anti-tumor activity in acute myeloid leukemia (AML) models (AACR 2022) - "These results justify testing the ZN-d5 and ZN-c3 combination or possibly the triple combination including azacitidine in AML patients independently of TP53 status. Due to synergism observed with these combination(s) and activity in samples from patients resistant to venetoclax, activity may be seen in patients with low sensitivity to Bcl-2 inhibitors or even in patients who progressed on venetoclax plus azacitidine."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • PTPRC • TP53

BH3 mimetics synergize with the Wee1 inhibitor ZN-c3 by activating caspases which induce DNA damage and degrade key proteins (AACR 2022) - "ZN-d5 or other BH3 mimetics caused caspase-mediated DNA damage and degraded relevant proteins such as Wee1 and RRM2 resulting in additive or synergistic anti-tumor activity when combined with ZN-c3. These results support a novel use of BH3 mimetics to activate caspase activity, independently of apoptosis induction, to significantly enhance the activity of DDR inhibitors such as ZN-c3"

IO biomarker • Oncology • BCL2 • BCL2L1 • CASP3 • CDK1 • RRM2

Phase 1/2 Study of ZN-d5 for the Treatment of Relapsed or Refractory Light Chain (AL) Amyloidosis (clinicaltrials.gov) - P1/2; N=135; Recruiting; Sponsor: K-Group Alpha, Inc.

New P1/2 trial • Amyloidosis

Research study to determine whether an investigational drug ZN-d5 is safe and effective in the treatment of Relapsed or Refractory Light Chain (AL) Amyloidosis (clinicaltrialsregister.eu) - P1/2; N=135; Ongoing; Sponsor: K-Group Alpha, Inc

Clinical • New P1/2 trial • Amyloidosis • Oncology

Zentalis Pharmaceuticals to Host Virtual Research and Development (R&D) Day on December 16, 2021 (GlobeNewswire) - "Zentalis Pharmaceuticals, Inc...is hosting a virtual R&D Day on December 16, 2021 from 11:00 a.m. to 12:00 p.m. EST. Additional details on the event are summarized below. Zentalis’ management team along with three Key Opinion Leaders (KOLs) will present preclinical science from multiple programs and clinical updates on ZN-d5, the Company’s oral, selective BCL-2 inhibitor for hematologic malignancies, and ZN-e4, the Company’s oral EGFR inhibitor for non-small cell lung carcinoma."

Clinical data • Preclinical • Hematological Malignancies • Lung Cancer • Non Small Cell Lung Cancer • Oncology

A Phase I Study of ZN-d5 in Chinese Subjects With Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1; N=30; Enrolling by invitation; Sponsor: Zentera Therapeutics HK Limited

Clinical • Monotherapy • New P1 trial • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

[VIRTUAL] Discovery of ZN-d5, a potent BCL-2 inhibitor with improved selectivity for BCL-2 (ESMO 2021) - "However, development of more selective BCL-2 inhibitors is warranted as thrombocytopenia, resulting from BCL-xL inhibition, is a common adverse reaction in patients receiving the approved BCL-2 inhibitor venetoclax. In summary, ZN-d5 is a promising new BCL-2 inhibitor with improved selectivity for BCL-2 vs other BCL-2 family members and demonstrates potent single-agent and combination activity in multiple in vivo tumor models. ZN-d5 is currently in phase 1 clinical trials for the treatment of NHL and AML."

IO biomarker • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Leukemia • Lymphoma • Oncology • Solid Tumor • BCL2L1