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10-K – Annual report [Section 13 and 15(d), not S-K Item 405]

(Filing, 10-K, MEI Pharma, SEP 5, 2017, View Source [SID1234520389])

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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.

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.