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MEI Pharma Announces Exclusive License Agreement with Presage Biosciences
for Voruciclib, An Oral, Selective CDK Inhib

September 5, 2017 — MEI Pharma, Inc. (Nasdaq: MEIP), an oncology company focused on the clinical development of novel therapies for cancer, reported that it has entered into a license agreement with Presage Biosciences, Inc. for voruciclib, a clinical-stage, oral and selective cyclin-dependent kinase (CDK) inhibitor. Under the terms of the agreement, MEI Pharma receives exclusive worldwide rights to develop, manufacture and commercialize voruciclib. In exchange, Presage will receive near-term payments of $2.9 million and additional potential payments of up to $181 million upon the achievement of certain development, regulatory and commercial milestones. Presage will also receive mid-single-digit tiered royalties on the net sales of any product successfully developed.
"We are very excited by this opportunity to add voruciclib to our growing pipeline of clinical-stage oncology drug candidates," said Daniel P. Gold, Ph.D., President and Chief Executive Officer of MEI Pharma. "Voruciclib is a selective CDK inhibitor, a class of drugs that has recently demonstrated significant clinical and commercial value, and is differentiated by its potent inhibition of CDK9. This is an attractive asset that comes with an established clinical safety profile, along with compelling pre-clinical data showing suppression of MCL1, a known mechanism of resistance to BCL2 inhibitors, and synergy with the FDA-approved BCL2 inhibitor venetoclax. We believe this provides a clear and efficient clinical development path forward in combination with venetoclax. We appreciate that Presage put their trust in us to execute this plan and we are eager to get started."
Voruciclib (formerly P1446A) has been tested in more than 70 patients in multiple Phase 1 studies and has been associated with manageable side effects consistent with other drugs in its class, including nausea, vomiting and diarrhea. In pre-clinical studies, voruciclib alone induces cell death in multiple patient-derived chronic lymphocytic leukemia (CLL) samples . In addition, voruciclib shows dose-dependent suppression of MCL1 at concentrations achievable with doses that appeared to be generally well tolerated in the Phase 1 studies. Studies have shown that MCL1 is an established resistance mechanism to the B-cell lymphoma 2 (BCL2) inhibitor venetoclax (marketed as Venclexta) .
"Voruciclib is a promising drug candidate with the potential to overcome mechanisms of drug resistance and significantly improve patient outcomes," said David Johnson, Chairman of Presage. "The management team at MEI Pharma has a proven track record in oncology therapeutic development and we believe they have the clinical, regulatory and CMC expertise to maximize the value of this asset. This transaction also enables us to focus our attention on identifying and advancing additional drug candidates and combinations using our powerful CIVO intratumoral microdosing platform.
There are currently two CDK inhibitors approved by the U.S. Food and Drug Administration, palbociclib (marketed as Ibrance) and ribociclib (marketed as Kisqali), both oral, selective CDK 4/6 inhibitors approved for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer in combination with hormonal therapy. A third, abemaciclib, was recently granted priority review by the FDA.

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MEI Pharma Announces Exclusive License Agreement with Presage Biosciences
for Voruciclib, An Oral, Selective CDK Inhibitor

On September 5, 2017 MEI Pharma, Inc. (Nasdaq: MEIP), an oncology company focused on the clinical development of novel therapies for cancer, reported that it has entered into a license agreement with Presage Biosciences, Inc. for voruciclib, a clinical-stage, oral and selective cyclin-dependent kinase (CDK) inhibitor (Press release, MEI Pharma, SEP 5, 2017, View Source [SID1234520396]). Under the terms of the agreement, MEI Pharma receives exclusive worldwide rights to develop, manufacture and commercialize voruciclib. In exchange, Presage will receive near-term payments of $2.9 million and additional potential payments of up to $181 million upon the achievement of certain development, regulatory and commercial milestones. Presage will also receive mid-single-digit tiered royalties on the net sales of any product successfully developed.

"We are very excited by this opportunity to add voruciclib to our growing pipeline of clinical-stage oncology drug candidates," said Daniel P. Gold, Ph.D., President and Chief Executive Officer of MEI Pharma. "Voruciclib is a selective CDK inhibitor, a class of drugs that has recently demonstrated significant clinical and commercial value, and is differentiated by its potent inhibition of CDK9. This is an attractive asset that comes with an established clinical safety profile, along with compelling pre-clinical data showing suppression of MCL1, a known mechanism of resistance to BCL2 inhibitors, and synergy with the FDA-approved BCL2 inhibitor venetoclax. We believe this provides a clear and efficient clinical development path forward in combination with venetoclax. We appreciate that Presage put their trust in us to execute this plan and we are eager to get started."

Voruciclib (formerly P1446A) has been tested in more than 70 patients in multiple Phase 1 studies and has been associated with manageable side effects consistent with other drugs in its class, including nausea, vomiting and diarrhea. In pre-clinical studies, voruciclib alone induces cell death in multiple patient-derived chronic lymphocytic leukemia (CLL) samples . In addition, voruciclib shows dose-dependent suppression of MCL1 at concentrations achievable with doses that appeared to be generally well tolerated in the Phase 1 studies. Studies have shown that MCL1 is an established resistance mechanism to the B-cell lymphoma 2 (BCL2) inhibitor venetoclax (marketed as Venclexta) .

"Voruciclib is a promising drug candidate with the potential to overcome mechanisms of drug resistance and significantly improve patient outcomes," said David Johnson, Chairman of Presage. "The management team at MEI Pharma has a proven track record in oncology therapeutic development and we believe they have the clinical, regulatory and CMC expertise to maximize the value of this asset. This transaction also enables us to focus our attention on identifying and advancing additional drug candidates and combinations using our powerful CIVO intratumoral microdosing platform.

There are currently two CDK inhibitors approved by the U.S. Food and Drug Administration, palbociclib (marketed as Ibrance) and ribociclib (marketed as Kisqali), both oral, selective CDK 4/6 inhibitors approved for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer in combination with hormonal therapy. A third, abemaciclib, was recently granted priority review by the FDA.

TG Therapeutics Announces Completion of Target Enrollment in the UNITY-CLL Phase 3 Trial

On September 5, 2017 TG Therapeutics, Inc. (NASDAQ: TGTX) reported that target enrollment for the UNITY-CLL Phase 3 trial has been achieved (Press release, Manhattan Pharmaceuticals, SEP 5, 2017, View Source [SID1234520379]). The UNITY-CLL Phase 3 trial is a randomized study of TG-1101 (ublituximab), the Company’s novel glycoengineered anti-CD20 monoclonal antibody, in combination with TGR-1202 (umbralisib), the Company’s PI3K delta inhibitor (together referred to as the U2 regimen), compared to an active control arm of obinutuzumab plus chlorambucil, in patients with both treatment naïve and relapsed or refractory Chronic Lymphocytic Leukemia (CLL). Per the protocol, the target enrollment was 175 patients in each the U2 arm and the active control arm. While target enrollment has been reached, in order to provide an opportunity for all patients already identified to participate, enrollment is expected to continue until mid-October. The UNITY-CLL Phase 3 trial is being conducted pursuant to a Special Protocol Assessment (SPA) agreement with the Food and Drug Administration (FDA).

Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer stated, "We are extremely pleased to announce the completion of target enrollment in the UNITY-CLL clinical trial, nearly 9 months earlier than our original projections. From the beginning, enrollment in this study has exceeded our expectations, putting us in position to deliver top-line data on the ORR endpoint earlier than anticipated, now expected in the second quarter of 2018. If positive, pursuant to our SPA, the ORR data may be used to support a filing for accelerated approval." Mr. Weiss continued, "We want to thank the UNITY-CLL Investigators, research staff, and their patients, for their participation in this important clinical research. Without their commitment and trust, advancing novel medicines would not be possible."

John Gribben, MD, DSc, of the Barts Cancer Institute in London, UK, and Global Study Chair for the UNITY-CLL study stated, "The design of the UNITY-CLL trial is a paradigm shift in the way we approach oncology research, allowing two novel drugs to be evaluated together in a single four-arm study for potential approval. The speed in which target enrollment has completed is even more impressive, considering the size and scope of this innovative study, which also underscores the need for new treatment options despite recent advances. I am eagerly looking forward to presenting results from this study next year."

Ian Flinn, MD, PhD, Director of the Blood Cancer Research Program, Sarah Cannon Research Institute, and a lead US enroller in the UNITY-CLL study stated, "We were pleased at Tennessee Oncology to not only lead enrollment in the first-in-human study of umbralisib, but to now be one of the leading enrollers to the Phase 3 UNITY-CLL trial. The rapid rate of enrollment for both the first-in-human study of umbralisib and the Phase 3 study UNITY study is a testament to the continued need for better, patient-friendly, easy to use, treatment options for both treatment naïve CLL patients and those relapsed or refractory to prior therapy. BTK intolerance and difficulties in delivering anti-bcl2 therapy are challenges for delivering effective chemo-free treatment options for many patients. Approval of the ublituximab + umbralisib regimen would provide new hope to many of those patients.

ABOUT UNITY-CLL PHASE 3 TRIAL

UNITY-CLL is a global Phase 3 randomized controlled clinical trial in patients with Chronic Lymphocytic Leukemia (CLL) that includes two key objectives: first, was to demonstrate contribution of each agent in the TG-1101 (ublituximab) + TGR-1202 (umbralisib) or U2 regimen, and second, to demonstrate superiority in Progression Free Survival (PFS) over the standard of care to support the submission for full approval of the combination. In addition, upon completion of enrollment, this trial will evaluate Overall Response Rate (ORR) for accelerated approval. The study initially randomized patients into four treatment arms: TG-1101 plus TGR-1202, TG-1101 single agent, TGR-1202 agent, and an active control arm of obinutuzumab plus chlorambucil. Pursuant to the Special Protocol Assessment (SPA) with the U.S. Food and Drug Administration (FDA), an early interim analysis was conducted to assess contribution of each single agent which allowed for early termination of both single agent arms.

Acceleron Announces Publication of Luspatercept Phase 2 Myelodysplastic Syndromes Study Results in The Lancet Oncology

On September 5, 2017 Acceleron Pharma Inc. (NASDAQ: XLRN), a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of innovative therapeutics to treat serious and rare diseases, reported that The Lancet Oncology has published results from the Phase 2 study of luspatercept in patients with lower-risk myelodysplastic syndromes (MDS) (Press release, Acceleron Pharma, SEP 5, 2017, View Source [SID1234520376]).

"The efficacy and safety results in this Phase 2 study support continued research into luspatercept for the treatment of refractory anemia which often requires red blood cell transfusions in lower-risk MDS patients," said Uwe Platzbecker, M.D., Professor of Hematology and Head of the MDS program at the University Hospital in Dresden, Germany. "This novel investigational therapy has the potential to address a significant need in MDS patients who currently have very limited options for managing chronic anemia. We have already begun exploring luspatercept’s activity across a range of MDS patient populations."

"We are pleased that The Lancet Oncology chose to publish these results," said Matthew Sherman, M.D., Chief Medical Officer of Acceleron. "The positive clinical activity demonstrated in this study informed our earlier decision to initiate the pivotal MEDALIST Phase 3 trial in lower-risk MDS, and we expect to report top-line results from this trial in mid-2018."

The article, entitled "Luspatercept for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes: a phase 2 dose-finding study with long-term extension study" is now available online and will be published in a future print issue of The Lancet Oncology. The journal also published online a companion Comment article, "Defeating anaemia in myelodysplastic syndromes: another step forward," by Valeria Santini, M.D., Associate Professor of Hematology at the University of Florence Medical School in Florence, Italy.

Phase 2 presentations of luspatercept in MDS presented at recent medical conferences include updated longer-term follow-up and new expansion cohort preliminary results beyond that incorporated in this publication. Presentations outlining these results are available online under the science page on the Company’s website at www.acceleronpharma.com.

The MEDALIST trial, a global Phase 3 study of luspatercept in lower-risk MDS patients, is fully enrolled and top-line results are expected in mid-2018. The MEDALIST trial enrolled patients who are ring sideroblast-positive, red blood cell transfusion dependent, and are erythropoiesis-stimulating agent (ESA)-refractory or ESA-treatment ineligible, based on erythropoietin levels greater than 200 units per liter at baseline. In early 2018, Acceleron and Celgene plan to initiate the COMMANDS Phase 3 trial in first-line, lower-risk MDS patients.

Luspatercept is an investigational product that is not approved for use in any country.

About Luspatercept

Luspatercept is a modified activin receptor type IIB fusion protein that acts as a ligand trap for members of the transforming growth factor-beta superfamily involved in the late stages of erythropoiesis (red blood cell production). Luspatercept regulates late-stage erythrocyte (red blood cell) precursor cell differentiation and maturation. This mechanism of action is distinct from that of erythropoiesis stimulating agents (ESAs), which stimulate the proliferation of early-stage erythrocyte precursor cells. Acceleron and Celgene are jointly developing luspatercept as part of a global collaboration. Phase 3 clinical trials are underway to evaluate the safety and efficacy of luspatercept in patients with myelodysplastic syndromes (the MEDALIST study) and in patients with beta-thalassemia (the BELIEVE study). For more information, please visit www.clinicaltrials.gov.

MEI Pharma Reports Fiscal Year 2017 Results

On September 5, 2017 MEI Pharma, Inc. (Nasdaq: MEIP), an oncology company focused on the clinical development of novel therapies for cancer, reported results for its fiscal year ended June 30, 2017 (Press release, MEI Pharma, SEP 5, 2017, View Source [SID1234520393]).

"We begin our new fiscal year with strong momentum, a maturing pipeline of clinical-stage oncology drug candidates and a healthy cash balance," said Daniel P. Gold, Ph.D., President and Chief Executive Officer of MEI Pharma. "We have made significant strides in the clinic over the past several months, underscored by the dosing of the first patients in the pivotal Phase 3 study of pracinostat in AML, as well as in the Phase 2 dose-optimization study of pracinostat in MDS. Meanwhile, we are very excited by the response and safety data that are emerging from the open-label study of our PI3K delta inhibitor ME-401. This program continues to exceed our high expectations and we look forward to the opportunity to present more data at an upcoming scientific meeting."

Financial Highlights

As of June 30, 2017, MEI Pharma had $53.6 million in cash, cash equivalents and short-term investments, with no outstanding debt. The Company believes its cash position will be sufficient to fund operations into calendar year 2019.
Cash expenditures were $16.5 million for the year ended June 30, 2017, compared to $17.9 million for 2016. Cash expenditures were $3.1 million for the fourth quarter ended June 30, 2017, compared to $3.5 million for the same period in 2016.
Research and development expenses were $7.2 million for the year ended June 30, 2017, compared to $13.4 million for 2016. The decrease was primarily due to a reduction in expenses related to pracinostat pursuant to the Helsinn License Agreement.
General and administrative expenses were $8.6 million for the year ended June 30, 2017, compared to $7.6 million for 2016. The increase was primarily due to professional service costs.
Revenues were $23.2 million for the year ended June 30, 2017, related to the Helsinn License Agreement. During the year ended June 30, 2017, the cost of research and development revenue was $5.0 million. Cost of research and development revenue is comprised primarily of reimbursable third-party pass-through costs.
Net income was $2.7 million, or $0.07 per share, for the fiscal year ended June 30, 2017, compared to a net loss of $20.9 million, or $0.61 per share for 2016.
Recent Clinical Milestones

First patient dosed in pivotal Phase 3 study of pracinostat in AML. In July 2017, the first patient was dosed in a pivotal Phase 3 study of the investigational drug candidate pracinostat in combination with azacitidine in adults with newly diagnosed acute myeloid leukemia (AML) who are unfit to receive intensive induction chemotherapy. The randomized, double-blind, placebo-controlled study will enroll approximately 500 eligible patients worldwide. Helsinn Healthcare, SA, a Swiss pharmaceutical company, has an exclusive license to develop, manufacture and commercialize pracinostat (Helsinn License Agreement), and is responsible for the conduct and funding of this Phase 3 study.
First patient dosed in Phase 2 dose-optimization study of pracinostat in MDS. In June 2017, the first patient was dosed in a Phase 2 dose-optimization study of pracinostat in combination with azacitidine in patients with high and very high risk myelodysplastic syndrome (MDS) who are previously untreated with hypomethylating agents. The two-stage study will be conducted at approximately 25 sites and is expected to enroll up to 120 patients. Data from the first stage is expected in the first quarter of 2018. MEI Pharma is responsible for the conduct of this Phase 2 study, the cost of which will be shared by Helsinn. Helsinn will be responsible for funding any further studies.
Genetic mutation data from Phase 2 study of pracinostat in AML. In June 2017, results from a mutational analysis of patients in the Phase 2 study of pracinostat and azacitidine in AML were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) and European Hematology Association (EHA) (Free EHA Whitepaper) annual meetings. The findings showed: 1) a statistically significant correlation between genetic mutations in the DNA methylation pathway and clinical response; 2) the mutation profile in the Phase 2 study was representative not only of the larger population of older AML patients, but common in MDS patients as well; and 3) that median overall survival was roughly equivalent in patients with mutations typically associated with de novo AML (18.1 months) and secondary AML (17.7 months). In addition, longitudinal sequencing analyses showed that continued treatment with pracinostat and azacitidine increases the rate of minimal residual disease (MRD) clearance.
Emerging data from Phase 1b study of ME-401 in CLL and follicular lymphoma. In May 2017, an independent safety review committee completed its review of the first cohort of six evaluable patients in an ongoing Phase 1b dose-escalation study of the Company’s oral PI3K delta inhibitor ME-401 in relapsed refractory chronic lymphocytic leukemia (CLL) and follicular lymphoma. The safety review committee found no dose-limiting toxicities, declared a minimum biologically effective dose (response rate > 50%) at the starting dose of 60 mg and recommended escalation to a 120 mg dose cohort. To date, the study has enrolled a total of 18 patients who are evaluable for safety, four of whom are still too early for a response assessment. The 18 patients have been on study for a median of approximately three months (range, 1-10 months) and no patients have discontinued due to adverse events or disease progression.