voruciclib (ME-522) / Lite Strategy, Presage - LARVOL DELTA

Advances in the Management of Relapsed/Refractory CLL and Richter Transformation (ICML 2025) - P=N/A, P2, P3 | "BRUIN CLL-321 is a phase 3, registrational study that evaluated pirtobrutinib compared to the investigator's choice of idelalisib plus rituximab (IdelaR) or bendamustine plus rituximab (BR) [23]...Nemtabrutinib is now being evaluated in the registrational, phase 3 BELLWAVE-010 trial (NCT05947851) for patients with R/R CLL, comparing nemtabrutinib plus venetoclax to venetoclax plus rituximab...An ongoing, open-label, first-in-human phase 1/2 study is evaluating the BTK degrader BGB-16673 as monotherapy in patients with R/R CLL [27, 28]...NX-2127 is an investigational, first-in-class BTK degrader currently being evaluated in a phase 1 trial for patients with relapsed or refractory B-cell malignancies, CLL [29, 30]...NX-5948 is another investigational and more selective BTK degrader in an ongoing Phase 1a/1b clinical trial...This trial aims to establish lisaftoclax plus acalabrutinib as a potential alternative to venetoclax-based BTKi combination..."

IO biomarker • Acute Myelogenous Leukemia • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • Small Lymphocytic Lymphoma • BCL2L1 • TP53

A Phase 1 Study of the Oral CDK9 Inhibitor Voruciclib in Combination with Venetoclax in Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) (ASH 2024) - P1 | "Background : Venetoclax in combination with hypomethylating agents (HMA) or low dose cytarabine is the standard of care for patients (pts) with newly diagnosed AML ineligible for intensive chemotherapy. Conclusion : The combination of voruciclib with venetoclax is well-tolerated and has activity in pts with AML and disease progression after venetoclax. Because of the rebound in peripheral blasts after 14 days off voruciclib, voruciclib administered on days 1-21 per cycle merits further evaluation."

Combination therapy • P1 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Pulmonary Disease • Thrombocytopenia • MCL1

A Phase 1 Study of the Oral CDK9 Inhibitor Voruciclib in Relapsed/Refractory (R/R) B-Cell Lymphoma (NHL) or Acute Myeloid Leukemia (AML) (ASH 2023) - P1 | "Voruciclib at doses up to 200 mg administered on 14 consecutive days on a 28-day cycle was well tolerated, with no DLTs observed, and no cardiovascular toxicities. There was no significant myelosuppression in pts with B-cell malignancies. As the safety profile suggested non-overlapping toxicities with venetoclax, the study is now evaluating voruciclib in combination with venetoclax in pts with R/R AML to exploit dual inhibition of Bcl-2 and Mcl-1."

IO biomarker • P1 data • Acute Myelogenous Leukemia • Anemia • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Constipation • Diffuse Large B Cell Lymphoma • Fatigue • Gastroenterology • Gastrointestinal Disorder • Graft versus Host Disease • Hematological Malignancies • Hepatology • Immunology • Interstitial Lung Disease • Lymphoma • Marginal Zone Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • BCL2 • MYC

Pharmacodynamic Analysis of Mcl-1 and RNA Pol IISer2 Phosphorylation in Blasts from Patients with Relapsed or Refractory Acute Myeloid Leukemia Treated on a Phase 1 Study of Venetoclax Plus Voruciclib (ASH 2024) - "Background : Patients with acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy are often treated with venetoclax in combination with hypomethylating agents (HMAs) or low dose cytarabine. Conclusions : The combination of venetoclax plus voruciclib demonstrated pharmacodynamic activity in AML, and modulation of Mcl-1 protein expression and RNA Pol II phosphorylation, both of which were associated with clinical response. These findings highlight the potential of indirectly targeting Mcl-1 through CDK9i to improve outcomes for patients with AML and underscore the importance of further investigating the mechanisms underlying the efficacy of the combination of venetoclax plus voruciclib in this context."

Clinical • P1 data • PK/PD data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ADGRG1 • CDK9 • ITGAM • MCL1

Orally Bioavailable CDK9 Inhibitor Voruciclib Downregulates Oncogenic Pathways in Leukemic Cells from Patients Treated on a Clinical Trial (ASH 2024) - P1 | "Conclusions Here we report that AML and CLL samples from patients treated with the CDK9i voruciclib on a clinical trial demonstrated downregulation of multiple oncogenic pathways, including MYC transcriptional targets and OxPhos, consistent with the predicted mechanism of action. Analysis of additional samples is ongoing."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2A1 • CD4 • CD8 • MCL1 • MYC

The oral CDK9 inhibitor voruciclib combined with venetoclax for patients with relapsed/refractory acute myeloid leukemia. (PubMed, Blood Neoplasia) - P1 | "Overall, the combination of voruciclib with venetoclax was tolerable in patients with relapsed/refractory AML, had antileukemic activity, and showed on-target effects in heavily pretreated patients with disease progression after venetoclax. This trial was registered at www.ClinicalTrials.gov as #NCT03547115."

Journal • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Pulmonary Disease • Thrombocytopenia • CDK9 • MCL1

A phase 1 study of the CDK9 inhibitor voruciclib in relapsed/refractory acute myeloid leukemia and B-cell malignancies. (PubMed, Blood Adv) - P1 | "Voruciclib treatment led to a decrease in MCL1 mRNA expression, downregulation of MYC and NF-κB transcriptional gene sets, and reduced phosphorylation of RNA polymerase II. Voruciclib on intermittent dosing was well tolerated, with no DLTs, paving the way for evaluation of the combination of voruciclib with venetoclax in patients with previously treated AML."

Journal • P1 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Constipation • Fatigue • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Interstitial Lung Disease • Leukemia • Oncology • Pneumonia • Pulmonary Disease • Transplantation • CDK9 • MYC

MEI Pharma to Consider Strategic Alternatives (Businesswire) - "MEI Pharma, Inc...today announced that its Board of Directors has determined unanimously to begin evaluation of the Company’s strategic alternatives, including potential transactions as well as an orderly wind down of the Company, if appropriate, in order to maximize the value of its assets for its stockholders...The Company intends to promptly discontinue the clinical development of voruciclib, while certain non-clinical activities related to MEI’s drug candidate assets will continue to be conducted by the Company....The Company expects to enter into consulting agreements with both Mr. Urso and Dr. Ghalie under which they will remain available to assist the Company in its strategic efforts."

Discontinued • Licensing / partnership • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

MEI Pharma Reports Third Quarter Fiscal Year 2024 Results and Operational Highlights (Businesswire) - "Recent Highlights...While the threshold was met to proceed to Cohort 2, following a strategic review the Company decided to continue to advance ME-344 via its ongoing development of a new formulation rather than through the addition of a new cohort of patients. The Company has already initiated research and development activity of the new formulation...The Company expects to provide an update on our formulation efforts in the first half of calendar 2025...Research and development expenses decreased by $9.9 million to $5.2 million for the quarter...The decrease was primarily related to a reduction in zandelisib program costs, as well as reduced personnel and related costs from our reductions in headcount. These decreases were partially offset by increases related to clinical trials, reformulation and manufacturing costs associated with ME-344 and increased clinical costs for the ongoing clinical study with voruciclib."

Commercial • Pipeline update • Trial status • Acute Myelogenous Leukemia • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

MEI Pharma Reports Third Quarter Fiscal Year 2024 Results and Operational Highlights (Businesswire) - "MEI expects to report clinical data from additional dose escalation and expansion cohorts of the ongoing Phase 1 clinical trial evaluating voruciclib plus venetoclax in patients with R/R AML during the remainder of calendar 2024....The Company has completed patient enrollment of the dose expansion cohort evaluating a 300 mg dose of voruciclib administered daily for 14 consecutive days in a 28-day cycle in combination with standard dose venetoclax. Additionally, MEI is enrolling dose escalation cohorts evaluating up to four dose levels of voruciclib starting at 150 mg administered daily for 21 consecutive days in a 28-day cycle in combination with venetoclax."

Enrollment status • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

MEI Pharma Reports Update from Clinical Study Evaluating Oral CDK9 Inhibitor Voruciclib in Combination with Venetoclax in Patients with Relapsed and Refractory Acute Myeloid Leukemia (Businesswire) - "MEI Pharma, Inc...reported initiation of enrollment in a 12-patient expansion cohort in the ongoing Phase 1 study evaluating voruciclib, an investigational selective oral cyclin-dependent kinase 9 ('CDK9') inhibitor, in combination with venetoclax (Venclexta), a B-cell lymphoma 2 ('BCL2') inhibitor, in relapsed and refractory ('R/R') acute myeloid leukemia ('AML') patients. The Safety Review Committee recommended initiating the expansion cohort after observing anti-leukemic activity in multiple heavily pretreated patients in the dose escalation cohorts, including responses, anticipated decreases in myeloid leukemia cell differentiation protein ('Mcl-1') in available patient samples, no overlapping toxicity or dose limiting toxicities, and favorable safety results to date."

Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

MEI Pharma Reports Second Quarter Fiscal Year 2024 Results and Operational Highlights (Businesswire) - "Expected Drug Candidate Pipeline Developments: (i) Voruciclib - Oral CDK9 inhibitor in Phase 1 Study: We expect to report clinical data from the dose escalation portion of the ongoing Phase 1 clinical trial evaluating voruciclib plus venetoclax in patients with R/R AML in the first calendar quarter of 2024; (ii) ME-344 – Mitochondrial inhibitor in Phase 1b Study: We have completed enrollment in Cohort 1 of the Phase 1b clinical study evaluating ME-344 plus bevacizumab in patients with relapsed colorectal cancer. We expect to report data from Cohort 1 in the first half of calendar-year 2024."

Enrollment status • P1 data • Acute Myelogenous Leukemia • Colorectal Cancer

MEI Pharma Reports Clinical Data on Oral CDK9 Inhibitor Voruciclib at ASH2023 (Businesswire) - P1 | N=100 | NCT03547115 | Sponsor: MEI Pharma, Inc. | "MEI Pharma....announced clinical data from the monotherapy dose escalation stage of the ongoing Phase 1 study evaluating voruciclib...is highlighted in a poster session at the 65th American Society of Hematology (ASH) Annual Meeting....Monotherapy Efficacy: In the 21 patients enrolled with AML, 1 patient at 100 mg achieved a morphologic leukemia-free state and 9 patients had disease stabilization, which lasted at least 3 months in 2 patients. In the 19 patients enrolled with B-cell malignancies, 4 patients had stable disease with a decrease in tumor size....Voruciclib Plus Venetoclax Combination: Initial Data - Voruciclib at doses up to 200 mg on the intermittent schedule have been administered in combination with venetoclax in patients with relapsed or refractory AML."

P1 data • Acute Myelogenous Leukemia

MEI Pharma Announces Acceptance of Abstract for Presentation at ASH 2023 (Businesswire) - "MEI Pharma, Inc...today announced that an abstract highlighting clinical data from the monotherapy dose escalation stage of the ongoing Phase 1 study evaluating voruciclib...alone and in combination with venetoclax (Venclexta)...in patients with acute myeloid leukemia (AML) or B-cell malignancies, will be presented during a poster session at the upcoming 65th American Society of Hematology (ASH) Annual Meeting and Exposition to be held December 9 – 12, 2023."

P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

MEI Pharma Reports Fiscal Year 2023 Results and Operational Highlights (Businesswire) - "Expected Drug Candidate Pipeline Developments: (i) Voruciclib - Oral CDK9 inhibitor in Phase 1 Study: Report clinical data from the ongoing Phase 1 clinical trial evaluating voruciclib plus Venclexta® (venetoclax) in patients with AML early in calendar 2024; (ii) ME-344 - Mitochondrial inhibitor in Phase 1b Study: Report clinical data from the Phase 1b clinical trial evaluating ME-344 plus Avastin® (bevacizumab) in patients with relapsed colorectal cancer in the first half of calendar-year 2024."

P1 data • Acute Myelogenous Leukemia • Colorectal Cancer

MEI Pharma and Infinity Pharmaceuticals Host Video Webcast Providing Overview and Update on Pending Merger to Advance Three Promising Clinical Oncology Candidates (Businesswire) - "MEI Pharma, Inc...and Infinity Pharmaceuticals, Inc...announced today that the companies will host a recorded joint video webcast that will be available at 8:00 am Eastern Time on June 19, 2023. On the webcast Mr. David Urso will provide an update on the pending merger and an overview of the combined company, which joins the expertise and resources of MEI and Infinity to advance a robust pipeline of three clinical-stage oncology drug candidates...the webcast includes commentary and discussion with Dr. Ezra Cohen, a recognized expert in the treatment of squamous cell carcinoma of the head & neck (SCCHN)) and recently the Chief, Division of Hematology-Oncology, and Associate Director of Clinical Science at UC San Diego Moores Cancer Center."

Clinical • M&A • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hematological Malignancies • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

MEI Pharma Announces Update of Ongoing Phase 1 Study Evaluating Oral CDK9 Inhibitor Voruciclib Alone and in Combination with Venetoclax in Patients with Acute Myeloid Leukemia or B-Cell Malignancies (Businesswire) - P1 | N=100 | NCT03547115 | Sponsor: MEI Pharma, Inc. | "MEI Pharma...announced an update to the Phase 1 study evaluating voruciclib...in patients with relapsed and refractory ('R/R') acute myeloid leukemia ('AML') or B-cell malignancies. These results demonstrate that, as of the data cut off, voruciclib alone or in combination with venetoclax (Venclexta®), a BCL2 inhibitor, was generally well tolerated with no significant myelosuppression. The results further demonstrated encouraging clinical activity in heavily pretreated patients administered voruciclib alone and at the initial dose level in combination with venetoclax. These early results are consistent with the hypothesized ability of voruciclib to inhibit MCL-1 via CDK 9 inhibition to address a common venetoclax resistance mechanism....'We look forward to disclosing more data from this study around year-end, including data from patients receiving higher doses of voruciclib plus venetoclax'..."

P1 data • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

Infinity Pharmaceuticals Reports Full Year 2022 Financial Results (Businesswire) - "Voruciclib, an oral CDK9 inhibitor, currently being studied in combination with venetoclax (VENCLEXTA®) in patients with hematologic malignancies. MEI has provided guidance that the ongoing Phase 1b trial is expected to report initial results from the combination regimen around the end of 2023. ME-344, a novel tumor selective mitochondrial inhibitor targeting the OXPHOS pathway, to be evaluated in combination with bevacizumab (AVASTIN®) in patients with relapsed colorectal cancer. MEI has provided guidance that data from the Phase 1b trial to support opening enrollment in an expansion cohort are expected to be reported around the end of 2023."

P1 data • Hematological Malignancies • Oncology • Solid Tumor

[VIRTUAL] New Targetable Pathways in Chronic Lymphocytic Leukemia (CLL) (SOHO 2021) - P1/2 | "AZD5991 is a highly selective BH3-mimetic that demonstrates high in vitro potency in MCL1-dependent cell lines with an IC50 <1 nM.7 We have demonstrated that direct MCL1 inhibition with AZD5991 disrupts survival of neoplastic B-cells in lymph-node mimicking conditions, induces mitochondrial dysfunction and cooperates with BCL2/X inhibitors in vitro and in vivo.8 A phase 1 clinical trial of AZD5991 alone or in combination with venetoclax in hematologic malignancies is ongoing (NCT03218683)...AMG-176 demonstrated synergy with venetoclax in AML models; however, it also caused cytopenias.9 AMG-176 was shown to induce apoptosis of CLL cells independent of prognostic markers and overcame the protective effect of stromal microenvironment.10 However, suppressive effects on hematopoiesis will likely become the dose- limiting factor in clinical trials of MCL1-targeting agents. The effect of MCL1 inhibition on cord blood-derived CD34+ cells was studied using a..."

IO biomarker • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • BCL2 • BCL2L1 • BCL2L2 • CD19 • CD34 • CDK7 • ROR1 • SYK

MEI Pharma and Infinity Pharmaceuticals Announce Definitive Merger Agreement to Advance Three Promising Clinical Oncology Candidates (Businesswire) - "MEI Pharma, Inc...and Infinity Pharmaceuticals, Inc...announced today that the companies entered into a definitive merger agreement for an all-stock transaction forming a company combining the expertise and resources of MEI and Infinity to advance a robust pipeline of three clinical-stage oncology drug candidates....'Along with voruciclib and ME 344, this gives us three promising clinical-stage programs that we believe have significant potential to deliver improved therapeutic options for patients'...We prioritized the initiation of a randomized, controlled Phase 2 clinical study combining eganelisib with pembrolizumab in head and neck cancer patients which is intended to demonstrate improved clinical benefit....The merger is expected to close in mid-2023, subject to approvals by MEI Pharma and Infinity shareholders, respectively, and other customary closing conditions."

M&A • New P2 trial • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hematological Malignancies • Oncology • Squamous Cell Carcinoma of Head and Neck

MEI Pharma Reports Second Quarter Fiscal Year 2023 Results and Operational Highlights (Businesswire) - "Expected Drug Candidate Pipeline Developments: (i) Voruciclib:...Report key clinical data from the ongoing Phase 1b trial evaluating voruciclib plus Venclexta® (venetoclax) in patients with acute myeloid leukemia around calendar year-end 2023; (ii) ME-344:...Report key clinical data from the Phase 1b clinical trial evaluating ME-344 plus Avastin in patients with relapsed colorectal cancer around calendar year-end 2023; (iii) Zandelisib:...Provide an update on Kyowa Kirin’s plans for continued zandelisib development in Japan for patients with relapsed or refractory indolent B-cell non-Hodgkin lymphomas."

Commercial • P1 data • Acute Myelogenous Leukemia • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

MEI Pharma Initiates Strategic Realignment (Businesswire) - "MEI Pharma, Inc...announced that it plans to initiate a realignment of its clinical development efforts following the discontinuation of global development outside Japan of its PI3K delta inhibitor, zandelisib. As part of the realignment, the company plans to streamline its organization towards the development of two earlier clinical-stage assets, voruciclib and ME-344....Expected Drug Candidate Pipeline Developments: Voruciclib – Oral cyclin-dependent kinase 9 (CDK9) inhibitor for the treatment of B-cell malignancies and acute myeloid leukemia, as well as solid tumors: After initiating dosing of the first patient in November, continue advancing the dosing of patient cohorts evaluating voruciclib in combination with Venclexta^® (venetoclax) in patients with acute myeloid leukemia in the ongoing Phase 1 study; Provide a clinical data update in CY2023. "

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

MEI Pharma Reports First Quarter Fiscal Year 2023 Results and Operational Highlights (Businesswire) - "Dose the first patient in the Phase 2 CORAL study evaluating zandelisib plus Venclexta® (venetoclax) and rituximab in patients with chronic lymphocytic leukemia by year-end 2022....Dose the first patient cohort of voruciclib in combination with Venclexta (venetoclax) in patients with acute myeloid leukemia by year-end 2022 in the Phase 1 study....Initiate a Phase 1b study evaluating ME-344 plus Avastin® (bevacizumab) in relapsed colorectal cancer patients in the first half of calendar year 2023."

New P1 trial • Trial status • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

A Phase 1 Dose-Escalation Study of the Oral CDK Inhibitor Voruciclib in Patients with Relapsed/Refractory B-Cell Malignancies or Acute Myeloid Leukemia (AML): Preliminary Results of the Completed Dose Escalation Stage in AML (ASH 2021) - P1 | "To date, in Groups I and II combined, 1 AML pt achieved a morphologic leukemia-free state, 2 AML pts achieved stable disease (SD), and 3 pts with B-cell malignancies had a best response of SD, including 1 FL pt who achieved a 42% reduction in SPD, and 1 CLL pt with relapsed disease after chemoimmunotherapy, venetoclax, and ibrutinib who had stable blood counts. Enrollment at 200 mg will continue in an expansion cohort in AML. A forthcoming protocol amendment will evaluate VORU in combination with venetoclax in pts with relapsed AML to exploit the dual inhibition of Bcl-2 and Mcl-1."

Clinical • IO biomarker • P1 data • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Inflammation • Leukemia • Lymphoma • Mantle Cell Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor • Transplantation • BCL2

MEI Pharma Reports Fiscal Year 2022 Results and Operational Highlights (Businesswire) - "Expected Drug Candidate Pipeline Developments: (i) Voruciclib - Oral CDK9 inhibitor for the treatment of B-cell malignancies and acute myeloid leukemia: Dose the first patient cohort of voruciclib in combination with Venclexta (venetoclax) in patients with acute myeloid leukemia by year-end 2022 in the Phase 1 study; (ii) ME-344 - Tumor selective mitochondrial inhibitor: Initiate a Phase 1b study evaluating ME-344 plus Avastin® (bevacizumab) in relapsed colorectal cancer patients in the first half of calendar year 2023."

New P1 trial • Trial status • Acute Myelogenous Leukemia • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Oncology • Solid Tumor