lacutoclax (LP-108) / Lupeng Pharma - LARVOL DELTA

A Phase 1, Multicenter, Open-Label, Dose-Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Clinical Activity of Orally Administered LP-108 (Lacutoclax) As Monotherapy and in Combination with Azacitidine in Subjects with Relapsed or Refractory Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML), or Acute Myeloid Leukemia (AML) (ASH 2024) - P1 | "We observed 4 CRc, 1PR and 2MFLS and 2 patients with improvement in its MDS status.Conclusions : Lacutoclax is safe with no apparent extra hematological toxicities and appears as a new anti BCL-2 agent in patients with refractory myeloid malignancies. This agent had encouraging efficacy as both monotherapy and in combination with azacitidine."

Clinical • Combination therapy • Monotherapy • P1 data • PK/PD data • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Novel Coronavirus Disease • Oncology • Thrombocytopenia

SAFETY AND EFFICACY OF LP-108, A NOVEL AND SELECTIVE BCL-2 INHIBITOR, IN CHINESE PATIENTS WITH RELAPSED OR REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA/SMALL LYMPHOCYTIC LYMPHOMA FROM A PHASE I STUDY (EHA 2024) - P1 | "BCL-2inhibitors such as venetoclax have shown efficacy in patients with CLL/SLL, including those who are heavily-pretreated or have unfavorable prognostic factors. LP-108 demonstrated promising and durable clinical activity and favorable tolerability in patients with R/RCLL/SLL, including those who progressed during/after or were intolerant to prior BTKi treatment."

Clinical • P1 data • Anemia • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • Thrombocytopenia

Dose-Escalation Study of Oral Administration of LP-108 as Monotherapy and in Combination With Azacitidine in Patients With Relapsed or Refractory MDS, CMML, or AML (clinicaltrials.gov) - P1 | N=36 | Active, not recruiting | Sponsor: Newave Pharmaceutical Inc | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Monotherapy • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • BCL2

AN UPDATE OF SAFETY AND EFFICACY RESULTS FROM PHASE 1 STUDY OF LP-108, A NOVEL AND SELECTIVE BCL-2 INHIBITOR, IN PATIENTS WITH RELAPSED OR REFRACTORY B-CELL NON-HODGKIN LYMPHOMAS (EHA 2023) - P1 | "Background: The effectiveness of BCL-2 inhibition in hematologic malignancies has been demonstrated by venetoclax, a globally approved BCL-2 inhibitor that requires weekly dose ramp-up to mitigate the risk of tumor lysis syndrome (TLS) and its efficacy in Chinese patients with non-Hodgkin lymphomas (NHL) is obscure. LP-108 was well tolerated up to 800 mg/day with daily dose ramp-up schedule and showed encouraging antitumor activity in multiple types of B-cell NHL, even in those who had prior BTKi exposure. BCL2, Phase I, Non-Hodgkin's lymphoma, Chronic lymphocytic leukemia"

Clinical • P1 data • Anemia • Chronic Lymphocytic Leukemia • Endocrine Disorders • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Hepatology • Infectious Disease • Leukemia • Leukopenia • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Metabolic Disorders • Nephrology • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pneumonia • Renal Disease • Respiratory Diseases • Small Lymphocytic Lymphoma • Thrombocytopenia

SAFETY AND EFFICACY OF LP-108 AS MONOTHERAPY AND COMBINED WITH AZACITIDINE IN PATIENTS WITH RELAPSED/REFRACTORY MYELODYSPLASTIC SYNDROMES, CHRONIC MYELOMONOCYTIC LEUKEMIA, OR ACUTE MYELOID LEUKEMIA (EHA 2023) - P1 | "LP-108 is an oral highly potent and selective inhibitor of BCL-2 with comparable or more potent in vitro inhibitory activity compared to the FDA approved oral BCL-2 inhibitor venetoclax. LP-108 as monotherapy and in combination with azacitidine was overall well tolerated with an acceptable safety profile for r/r MDS, CMML, and AML pts. Notably, the combination was associated with encouraging efficacy including ORR and PFS. Swimmers' plot of patients in Arm 1 (A) and Arm 2 (B)."

Clinical • Monotherapy • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology

A Phase I Study of LP-108 in Patients With Relapsed or Refractory B-cell Lymphoma (clinicaltrials.gov) - P1 | N=74 | Recruiting | Sponsor: The First Affiliated Hospital with Nanjing Medical University | Trial completion date: Dec 2022 ➔ Dec 2023 | Trial primary completion date: Apr 2022 ➔ Dec 2023

Trial completion date • Trial primary completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Dose-Escalation Study of Oral Administration of LP-108 as Monotherapy and in Combination With Azacitidine in Patients With Relapsed or Refractory MDS, CMML, or AML (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Newave Pharmaceutical Inc | Trial completion date: Dec 2022 ➔ Jan 2025 | Trial primary completion date: Dec 2022 ➔ Jan 2025

Combination therapy • Monotherapy • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • BCL2

A Study to Assess Safety and Preliminary Efficacy of LP-108 Combined With Azacitidine In Subjects With AML, MDS, CMML (clinicaltrials.gov) - P1 | N=198 | Recruiting | Sponsor: Guangzhou Lupeng Pharmaceutical Company LTD. | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

A Study to Assess Safety and Preliminary Efficacy of LP-108 Combined With Azacitidine In Subjects With AML, MDS, CMML (clinicaltrials.gov) - P1 | N=198 | Not yet recruiting | Sponsor: Guangzhou Lupeng Pharmaceutical Company LTD.

New P1 trial • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Phase 1 study of LP-108 as monotherapy and in combination with azacitidine in patients with relapsed or refractory myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), or acute myeloid leukemia (AML). (ASCO 2022) - P1 | "LP-108 is an oral highly potent and selective inhibitor of BCL-2 with comparable or more potent in vitro inhibitory activity as compared to the FDA approved oral BCL-2 inhibitor venetoclax...Hydroxyurea is allowed prior to and during treatment...Enrollment to Arm 2 is pending. Arm 1 Dose Escalation Scheme (LP-108 monotherapy)."

Clinical • Combination therapy • Monotherapy • P1 data • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CYP3A4

PHASE 1 STUDY OF LP-108, A SELECTIVE BCL-2 INHIBITOR, IN PATIENTS WITH RELAPSED OR REFRACTORY B-CELL NON-HODGKIN LYMPHOMA (EHA 2022) - P1 | "Globally approved BCL-2 inhibitor venetoclax has shown efficacies in certain hematologic malignancies (HMs) but requires weekly ramp-up to the target dose to mitigate the risk of tumor lysis syndrome (TLS). Conclusion LP-108 showed favorable safety profile up to 600 mg with daily dose ramp-up schedule, and antitumor activity in patients with r/r B-cell NHL. Dose escalation beyond 600 mg and further dose expansion are ongoing."

Clinical • P1 data • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukopenia • Lymphoma • Metabolic Disorders • Nephrology • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Renal Disease • Thrombocytopenia

Dose-Escalation Study of Oral Administration of LP-108 as Monotherapy and in Combination With Azacitidine in Patients With Relapsed or Refractory MDS, CMML, or AML (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Newave Pharmaceutical Inc | Trial primary completion date: Jun 2022 ➔ Dec 2022

Combination therapy • Monotherapy • Trial primary completion date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • BCL2

[VIRTUAL] Beyond BCL-2 Inhibition in Acute Myeloid Leukemia: Other Approaches to Leverage the Apoptotic Pathway (SOHO 2021) - "However, 10–50% of newly diagnosed patients with AML may not respond to venetoclax and HMA or LDAC, and 3–15% patients may not respond to venetoclax with intensive or non-intensive chemotherapy.1–6 In addition, up to 40% of responding patients may relapse with low rates of response of 20% to salvage therapy and poor overall survival of 2 months after relapse.7 Clinical and biological factors associated with primary and acquired resistance to venetoclax include secondary AML, monocytic differentiation, complex cytogenetics, mutations in TP53, BAX, dependence on other anti- apoptotic proteins, altered metabolism of nicotinamide, fatty acids, and oxidative phosphortylation.3,8–14 Several novel inhibitors of BCL-2 are currently being tested in clinic, including BGB 11417, APG-2575, LP-108 and others...There is strong pre-clinical rationale for targeting MCL-1 alone as well as in conjunction with BCL-2 inhibition in AML.15 Recently several selective and highly potent MCL-1..."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Solid Tumor • BCL2L1 • BIRC5 • CFLAR • MDM2 • TNFRSF10A • TNFRSF10B • XIAP

A Phase I Study of LP-108 in Patients With Relapsed or Refractory B-cell Lymphoma (clinicaltrials.gov) - P1; N=74; Recruiting; Sponsor: The First Affiliated Hospital with Nanjing Medical University; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Dose-escalation Study of Oral Administration of LP-108 in Patients With Relapsed or Refractory Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML), or Acute Myeloid Leukemia (AML) (clinicaltrials.gov) - P1; N=36; Recruiting; Sponsor: Newave Pharmaceutical Inc; Not yet recruiting ➔ Recruiting; Initiation date: Mar 2020 ➔ Jul 2020

Clinical • Enrollment open • Trial initiation date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

A Phase I Study of LP-108 in Patients With Relapsed or Refractory B-cell Lymphoma (clinicaltrials.gov) - P1; N=74; Not yet recruiting; Sponsor: The First Affiliated Hospital with Nanjing Medical University

Clinical • New P1 trial • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Dose-escalation Study of Oral Administration of LP-108 in Patients With Relapsed or Refractory Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML), or Acute Myeloid Leukemia (AML) (clinicaltrials.gov) - P1; N=36; Not yet recruiting; Sponsor: Newave Pharmaceutical Inc; Initiation date: Dec 2019 ➔ Mar 2020

Clinical • Trial initiation date