On June 5, 2018 Verastem, Inc. (President and CEO: Robert Forrester)(NASDAQ:VSTM) and Yakult Honsha Co., Ltd. (President: Takashige Negishi)(Tokyo:2267), reported their entry into an exclusive licensing agreement for Yakult to develop and commercialize Verastem’s duvelisib, a first-in-class oral dual inhibitor of phosphoinositide 3-kinase (PI3K)-delta and PI3K-gamma, for the treatment, prevention or diagnosis of all oncology indications in Japan (Press release, Verastem, JUN 5, 2018, View Source;p=RssLanding&cat=news&id=2353165 [SID1234527169]). Verastem’s New Drug Application (NDA) for duvelisib is currently under review with the U.S. Food and Drug Administration (FDA) and is seeking full approval for the treatment of relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and accelerated approval for the treatment of relapsed or refractory follicular lymphoma (FL). On April 9, 2018, Verastem announced that the FDA had accepted the NDA for filing with Priority Review.

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Under the terms of the agreement, Verastem will receive a one-time upfront payment of $10 million from Yakult. Verastem is eligible to receive up to an additional $90 million if certain future pre-specified development and commercialization milestones are successfully achieved by Yakult, plus double-digit royalties based on future net sales of duvelisib in Japan. In exchange, Yakult will receive exclusive rights to develop and commercialize duvelisib in Japan, at its own cost and expense. Yakult will also fund certain global development costs on a pro-rata basis. Verastem will retain all rights to duvelisib outside of Japan.

"In Japan, current therapies to treat CLL/SLL and FL are extremely limited and duvelisib has robust clinical data supporting its efficacy and safety in both indications, which we can build upon," said Masanori Ito, Head of Pharmaceutical Business Division/Managing Executive Officer, Member of the Board of Yakult. "We are eager to collaborate with Verastem to develop duvelisib in these initial hematologic malignancies, and then plan to later expand development to include the additional indications of PTCL and DLBCL. We believe this collaboration underscores our commitment to innovation, growing our oncology franchise, and commercializing medicines that positively impact the lives of patients in Japan."

"This agreement is an important, validating achievement for both duvelisib and Verastem Oncology and speaks to the significant global potential of this novel therapeutic for a broad range of hematologic malignancies," said Robert Forrester, President and Chief Executive Officer of Verastem. "Yakult is an established oncology leader in Japan that successfully markets several branded anti-cancer therapies, including Elplat and Campto. We look forward to working with the world-class development, regulatory and commercial teams at Yakult as they advance oral duvelisib toward commercialization in Japan."

About Duvelisib

Duvelisib is a first-in-class investigational oral, dual inhibitor of phosphoinositide 3-kinase (PI3K)-delta and PI3K-gamma, two enzymes known to help support the growth and survival of malignant B-cells and T-cells. PI3K signaling may lead to the proliferation of malignant B- and T-cells and is thought to play a role in the formation and maintenance of the supportive tumor microenvironment.1,2,3 Duvelisib was evaluated in late- and mid-stage extension trials, including DUO, a randomized, Phase 3 monotherapy study in patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL),4 and DYNAMO, a single-arm, Phase 2 monotherapy study in patients with refractory indolent non-Hodgkin lymphoma (iNHL).5 Both DUO and DYNAMO achieved their primary endpoints. Verastem Oncology’s New Drug Application (NDA) requesting the full approval of duvelisib for the treatment of patients with relapsed or refractory CLL/SLL, and accelerated approval for the treatment of patients with relapsed or refractory follicular lymphoma (FL) was accepted for filing by the U.S. Food and Drug Administration (FDA), granted Priority Review and assigned a target action date of October 5, 2018. Duvelisib is also being developed by Verastem Oncology for the treatment of peripheral T-cell lymphoma (PTCL), and is being investigated in combination with other agents through investigator-sponsored studies.6 Information about duvelisib clinical trials can be found on www.clinicaltrials.gov.

On June 5, 2018 Verastem, Inc. (President and CEO: Robert Forrester)(NASDAQ:VSTM) and Yakult Honsha Co., Ltd. (President: Takashige Negishi)(Tokyo:2267), reported their entry into an exclusive licensing agreement for Yakult to develop and commercialize Verastem’s duvelisib, a first-in-class oral dual inhibitor of phosphoinositide 3-kinase (PI3K)-delta and PI3K-gamma, for the treatment, prevention or diagnosis of all oncology indications in Japan (Press release, Verastem, JUN 5, 2018, View Source;p=RssLanding&cat=news&id=2353165 [SID1234527168]). Verastem’s New Drug Application (NDA) for duvelisib is currently under review with the U.S. Food and Drug Administration (FDA) and is seeking full approval for the treatment of relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and accelerated approval for the treatment of relapsed or refractory follicular lymphoma (FL). On April 9, 2018, Verastem announced that the FDA had accepted the NDA for filing with Priority Review.

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Under the terms of the agreement, Verastem will receive a one-time upfront payment of $10 million from Yakult. Verastem is eligible to receive up to an additional $90 million if certain future pre-specified development and commercialization milestones are successfully achieved by Yakult, plus double-digit royalties based on future net sales of duvelisib in Japan. In exchange, Yakult will receive exclusive rights to develop and commercialize duvelisib in Japan, at its own cost and expense. Yakult will also fund certain global development costs on a pro-rata basis. Verastem will retain all rights to duvelisib outside of Japan.

"In Japan, current therapies to treat CLL/SLL and FL are extremely limited and duvelisib has robust clinical data supporting its efficacy and safety in both indications, which we can build upon," said Masanori Ito, Head of Pharmaceutical Business Division/Managing Executive Officer, Member of the Board of Yakult. "We are eager to collaborate with Verastem to develop duvelisib in these initial hematologic malignancies, and then plan to later expand development to include the additional indications of PTCL and DLBCL. We believe this collaboration underscores our commitment to innovation, growing our oncology franchise, and commercializing medicines that positively impact the lives of patients in Japan."

"This agreement is an important, validating achievement for both duvelisib and Verastem Oncology and speaks to the significant global potential of this novel therapeutic for a broad range of hematologic malignancies," said Robert Forrester, President and Chief Executive Officer of Verastem. "Yakult is an established oncology leader in Japan that successfully markets several branded anti-cancer therapies, including Elplat and Campto. We look forward to working with the world-class development, regulatory and commercial teams at Yakult as they advance oral duvelisib toward commercialization in Japan."

About Duvelisib

Duvelisib is a first-in-class investigational oral, dual inhibitor of phosphoinositide 3-kinase (PI3K)-delta and PI3K-gamma, two enzymes known to help support the growth and survival of malignant B-cells and T-cells. PI3K signaling may lead to the proliferation of malignant B- and T-cells and is thought to play a role in the formation and maintenance of the supportive tumor microenvironment.1,2,3 Duvelisib was evaluated in late- and mid-stage extension trials, including DUO, a randomized, Phase 3 monotherapy study in patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL),4 and DYNAMO, a single-arm, Phase 2 monotherapy study in patients with refractory indolent non-Hodgkin lymphoma (iNHL).5 Both DUO and DYNAMO achieved their primary endpoints. Verastem Oncology’s New Drug Application (NDA) requesting the full approval of duvelisib for the treatment of patients with relapsed or refractory CLL/SLL, and accelerated approval for the treatment of patients with relapsed or refractory follicular lymphoma (FL) was accepted for filing by the U.S. Food and Drug Administration (FDA), granted Priority Review and assigned a target action date of October 5, 2018. Duvelisib is also being developed by Verastem Oncology for the treatment of peripheral T-cell lymphoma (PTCL), and is being investigated in combination with other agents through investigator-sponsored studies.6 Information about duvelisib clinical trials can be found on www.clinicaltrials.gov.

On June 4, 2018 Transgene (Paris:TNG), a biotech company that designs and develops virus-based immunotherapies against cancers and infectious diseases, and University of Leeds, reported that new clinical data1 obtained with Pexa-Vec further demonstrate anti-tumor activity after intravenous (i. v.) infusion (Press release, Transgene, JUN 4, 2018, View Source [SID1234621826]). These data were presented by Dr. Alan Anthoney (University of Leeds) in a poster presentation at the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, June 4, in Chicago .

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These first clinical results confirm Pexa-Vec’s activation of anti-tumor immunity and targeted oncolytic activity. The key findings of the trial show:

selective expression and replication of Pexa-Vec in the tumor tissues;
induction of a robust anti-tumor immune response:
with the stimulation of an adaptive response (T cells) targeted to tumor specific antigens,
the activation of innate immune response (NK cells), and
an elevation of cytokines associated with immune stimulation;
one partial and one complete necrosis of tumors among the patients with colorectal cancer and liver metastases (pathological responses);
upregulation of PD-L1 and PD-1 signaling molecules, a finding that strongly supports the rationale for combining Pexa-Vec with anti-PD-1 inhibitors.
Dr Alan Anthoney, Consultant in Medical Oncology at Leeds Teaching Hospitals, Senior Lecturer in the Institute of Cancer & Pathology at the University of Leeds and principal investigator of the trial, said: "We are very encouraged to report that a single IV administration of Pexa-Vec displayed cytolytic activity at tumor sites, where it elicited a robust activation of tumor-antigen specific immune cells. In one patient with colorectal cancer liver metastasis a complete pathological response has been observed. These data clearly support the anti-tumor activity of Pexa-Vec. The final data from this trial will be published in an upcoming paper. Our decision to lead this clinical trial, investigating the potential of new weapons against cancers, testifies to our commitment at Leeds University and Leeds Teaching Hospitals NHS Trust to evaluate new innovative options that might improve the lives of our patients with cancer."

Maud Brandely, Chief Medical Officer of Transgene, added: "These very positive translational data confirm the targeted oncolytic activity and the potential of Pexa-Vec in advanced stages cancers. The observed upregulation of PD-1 and PD-L1 positive pathways strongly supports the rationale for combining Pexa-Vec with anti-PD-1 immunotherapies, which is the focus of an ongoing Phase 1/2 trial in the first-line treatment of liver cancer (HCC). These data are also crucial for our next generation of multifunctional oncolytic viruses based on our Invir.IOTM platform: this trial clearly shows that Vaccinia virus based immunotherapeutics can reach the tumor sites after i. v. administration, and selectively replicate within cancer cells. This neoadjuvant trial is the first clinical trial led by Transgene to readout this year. We look forward to announcing additional clinical results this year, not only with Pexa-Vec, but also on our four other clinical-stage immunotherapeutics."

About the Pexa-Vec "neo-adjuvant" trial:
This clinical study is aimed at evaluating the biological effects of pre-operative intravenous administration of Pexa-Vec prior to planned surgical resection of locally advanced/poor prognosis or metastatic cancers. This single center, open label, non-randomized trial recruited 9 patients including 8 evaluable patients (3 with metastatic melanoma and 5 with colorectal cancer metastases to the liver). They received a single intravenous dose of 1×109 pfu of Pexa-Vec, 14 days prior to planned surgery. Up to 6 blood samples were collected pre- and post- injection for each patient. Imaging was performed prior at baseline and within 7 days prior to surgery. Tumor tissue was collected at surgery for histologic and translational assessments.
University of Leeds is the sponsor of the trial that was supported by Transgene and run through the NIHR Clinical Research Facility at St James’ Hospital, Leeds.

The poster is available on Transgene’s website.

About Pexa-Vec
Pexa-Vec (JX594) is an oncolytic immunotherapeutic based on an oncolytic vaccinia virus armed with a GM-CSF gene that promotes an anti-tumor immune response. Pexa-Vec is designed to selectively target and destroy cancer cells through three different mechanisms of action: selectively destroy cancer cells through the direct lysis (breakdown) of cancer cells through viral replication, reduce the blood supply to tumors through vascular disruption, and stimulate the body’s immune response against cancer cells.
Pexa-Vec is currently being evaluated in a Phase 3 trial in hepatocellular carcinoma (HCC, liver cancer) in combination with sorafenib (current standard of care). Other trials evaluating the oncolytic virus in solid tumors are underway and expected to readout in 2018, including a Phase 2 trial in combination with nivolumab (HCC).
Transgene has exclusive rights to develop and commercialize Pexa-Vec for the treatment of solid tumors in Europe. Its partner SillaJen, Inc. is focused on developing Pexa-Vec for the North American market and has also granted exclusive development and commercial rights to Pexa-Vec in Hong Kong and The People’s Republic of China to Lee’s Pharmaceutical.

On June 4, 2019 Calithera Biosciences, Inc. (Nasdaq:CALA), a clinical stage biotechnology company focused on the development of novel cancer therapeutics, reported that clinical data from its lead product candidate CB-839, a novel glutaminase inhibitor, will be presented at the 54th Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), which is being held from June 1 to June 5, 2018 in Chicago, Illinois (Press release, Calithera Biosciences, JUN 4, 2018, View Source [SID1234535239]). This is the first presentation of the Case Western investigator-sponsored phase 1/2 trial evaluating CB-839 in combination with capecitabine in patients with treatment refractory advanced solid tumors. The combination demonstrated a median progression free survival of 26 weeks in seven patients with treatment-refractory advanced colorectal cancer harboring a PIKC3A mutation who had disease progression on at least one prior fluoropyrimidine-containing regimen. The data will be presented on Monday June 4, 2018 in the Developmental Therapeutics Poster Session from 8:00 a.m.-11:30 a.m. CT (Abstract #2562, Board 388).

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"Investigator sponsored studies are an important part of our strategy to develop CB-839 broadly across cancer indications," said Susan M. Molineaux, Ph.D., founder, Chief Executive Officer and President of Calithera Biosciences. "We are grateful to the investigators and Stand Up 2 Cancer for their contributions to this ongoing trial."

Dr. Jennifer Eads from Case Comprehensive Cancer Center will present the results in a poster entitled, "Phase 1 clinical trial of the glutaminase inhibitor CB-839 plus capecitabine in patients with advanced solid tumors." The phase 1 portion of the trial is designed to determine safety and the recommended dose of the combination of CB-839 and capecitabine in patients with advanced treatment refractory solid tumors, while the phase 2 portion of the trial is designed to evaluate activity of the regimen in patients with late line PIK3CA mutant colorectal cancer. To date, 16 patients have been enrolled, including 12 patients with colorectal cancer. In the dose escalation phase of the trial, there were no dose limiting toxicities and CB-839 plus capecitabine was well tolerated at full dose of CB-839. The recommended phase 2 dose for the combination is CB-839 800 mg BID with capecitabine 1000 mg/m2 BID. In patients with late-line colorectal cancer that had progressed on at least one prior fluoropyrimidine-containing regimen, the median PFS was 26 weeks for patients with PIK3CA mutated cancer (n=7) and 16 weeks for patients with PIK3CA wild-type cancer (n=5, p=0.058). The phase 2 portion of this study in patients with PIK3CA mutant colorectal cancer is ongoing.

About CB-839

Calithera’s lead product candidate, CB-839, is a potent, selective, reversible and orally bioavailable inhibitor of glutaminase. CB-839’s onco-metabolism activity takes advantage of the unique metabolic requirements of tumor cells and cancer-fighting immune cells such as cytotoxic T-cells. It is currently being evaluated in Phase 2 clinical trials in multiple tumor types in combination with standard of care agents

On June 4, 2018 Euronext Paris: FR0010331421 – IPH) reported updated preliminary clinical data from an ongoing Phase I dose escalation and expansion study evaluating the safety and efficacy of the combination of monalizumab, a first-in-class monoclonal antibody targeting NK and T cell checkpoint receptor NKG2A, with durvalumab in patients with recurrent/metastatic microsatellite-stable colorectal cancer (MSS-CRC) (Press release, Innate Pharma, JUN 4, 2018, View Source [SID1234527252]). This trial is being conducted by MedImmune, AstraZeneca’s global biologics research and development arm, through a co-development and commercialization agreement.

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In a poster presentation made at the Gastrointestinal (Colorectal) Cancer session on Sunday, June 3 2018, during the annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), the combination of monalizumab and durvalumab showed encouraging anti-tumor activity in this difficult-to-treat patient subset.

"The preliminary data so far suggest that the combination of monalizumab and durvalumab may hold promise in some patients with MSS-CRC, a population historically unresponsive to PD-1/L1 therapy", said study investigator Neil H. Segal, MD., PhD., medical oncologist at Memorial Sloan Kettering Cancer Center, New York.

Pierre Dodion, Chief Medical Officer at Innate Pharma, added: "We are encouraged by the preliminary results from the ongoing trial observed in a heavily pretreated MSS-CRC patient population. These data have prompted our partner AstraZeneca/MedImmune to further expand the study with additional patient cohorts to explore the novel combination of this first-in-class antibody, monalizumab, with durvalumab on top of current standard of care therapies in patients with less heavily pretreated disease".

Key findings from the MSS-CRC expansion cohort:

Updated preliminary clinical data on the expansion cohort of microsatellite-stable colorectal cancer patients (MSS-CRC) presented at ASCO (Free ASCO Whitepaper) are based on the cut-off date of April 23, 2018. Forty patients are evaluable for safety and 39, for efficacy. Thirty five (88%) patients had 2 or more prior lines of therapy for recurrent/metastatic disease. Efficacy data show an overall response rate (ORR) of 8%, with confirmed partial response in 3 patients (8%) and stable disease (SD) in 11 patients (28%), including 3 SD patients with tumor reduction who continued therapy for >200 days. The median duration of response was 16.1 weeks at the cut-off date. Data demonstrated a disease control rate (DCR) of 31% at 16 weeks.