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FLX Bio Announces Clinical Trial Collaboration Agreement with Merck for Ongoing Phase 1/2 Study of FLX475

On November 5, 2018 FLX Bio, Inc., a clinical-stage, biopharmaceutical company focused on the development of oral small-molecule drugs that target drivers of cancer and other immune-related disorders, reported that it has established a clinical trial collaboration agreement with Merck (known as MSD outside the U.S. and Canada) to conduct a Phase 1/2 study evaluating the safety and efficacy of the combination of KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy , and FLX Bio’s investigational oral small molecule CCR4 inhibitor, FLX475, in patients with multiple types of cancer (Press release, FLX Bio, NOV 5, 2018, View Source [SID1234530726]).

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The open-label, dose-escalation and cohort expansion Phase 1/2 study is enrolling patients with multiple types of cancer at leading cancer centers across the United States, Australia and Asia. In addition to evaluating the safety and tolerability of FLX475 as a monotherapy and in combination with pembrolizumab, the study will evaluate changes in the tumor microenvironment and the antitumor activity of both monotherapy and combination therapy. For more information please visit clinicaltrials.gov identifier NCT03674567.

"We are extremely pleased to collaborate with Merck, an established leader in the field of cancer immunotherapy," said Brian Wong, M.D., Ph.D., CEO of FLX Bio. "KEYTRUDA is an anti-PD1 immunotherapy that has demonstrated efficacy in a range of cancers. FLX475 targets a novel mechanism to selectively inhibit the recruitment of regulatory T cells (Treg) into the tumor, where Treg potentially suppress the anti-tumor immune response; thus FLX475 has the potential to deepen and broaden the efficacy of KEYTRUDA when combined. We are excited to collaborate with the Merck team to evaluate the efficacy of a combination of FLX475 and KEYTRUDA which we believe could substantially improve patient outcomes."

Keytruda is a registered trademark of Merck Sharp & Dohme Corp, a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

About FLX475
FLX475 is a best-in-class oral, small molecule antagonist of CCR4 which selectively blocks suppressive regulatory T cells in tumor tissue and promotes a durable anti-tumor immune response. FLX Bio has completed a study of FLX475 in healthy volunteers, demonstrating that the compound is safe with excellent pharmacokinetic and pharmacodynamic properties. In preclinical studies, FLX475 inhibited tumor growth and increased tumor regression as a single agent. In addition, FLX475 enhanced the anti-tumor effects of various checkpoint inhibitors as well as immune agonist antibodies. FLX475 also has the potential to enhance cell-based immunotherapies such as CAR-T and cancer vaccines. In contrast to depleting antibody approaches, FLX475 selectively blocks the recruitment of regulatory T cells to the tumor site and does not deplete cells beneficial to an anti-tumor response or regulatory T cells in healthy tissue.

Crescendo Biologics announces early licensing by Takeda of first oncology-targeted Humabody®

On November 5, 2018 Crescendo Biologics Ltd (Crescendo), the drug developer of novel, targeted T-cell enhancing therapeutics, reported that Takeda Pharmaceutical Company Limited (Takeda), has exercised an option under its existing, multi-target collaboration and license agreement (Press release, Crescendo Biologics, NOV 5, 2018, View Source [SID1234530725]). Takeda has taken an exclusive licence to Humabodies directed to one of its oncology targets.

This licence option exercise comes substantially earlier than planned and marks the highly successful delivery and further pre-clinical evaluation by Takeda of Humabody leads meeting its stringent criteria.
Dr Peter Pack, CEO of Crescendo, commented:

"The team at Crescendo has made great progress on our Humabody programmes, working closely with the Takeda team. To date, we have met all the technical milestones on time or earlier than planned, which is proof of our excellent collaboration. We are delighted that the option to license has been taken by Takeda ahead of schedule and look forward to further future successes."

Chris Arendt, Head, Oncology Drug Discovery Unit & Immunology Unit, Takeda, commented:
"At Takeda, we continue to research diverse modalities to bring transformative treatments to patients with cancer. Our decision to exercise the licence was based on the quality of the Humabody leads and the potential we see to develop improved and differentiated immuno-oncology therapies."

Takeda’s option is part of the existing multi-target collaboration and licence agreement announced in October 2016 where Takeda received the right to develop and commercialise Humabody-based therapeutics resulting from the collaboration. Under the agreement, Crescendo is eligible to receive clinical development, regulatory and sales-based milestone payments of up to $754 million plus royalties on Humabody-based product sales by Takeda.

MEI Pharma and Kyowa Hakko Kirin Announce License Agreement to Develop and Commercialize ME-401 in Japan

On November 5, 2018 MEI Pharma, Inc. (NASDAQ: MEIP) and Kyowa Hakko Kirin Co., Ltd. (Tokyo: 4151, "Kyowa Hakko Kirin"), reported the execution of a license agreement granting Kyowa Hakko Kirin exclusive rights to develop and commercialize ME-401 in Japan ("License Agreement"). ME-401 is MEI’s phosphatidylinositol 3-kinase ("PI3K") delta inhibitor being developed by MEI for the treatment of patients with B-cell malignancies (Press release, Kyowa Hakko Kirin, NOV 5, 2018, View Source [SID1234530724]). MEI is planning to initiate a Phase 2 study to evaluate patients with follicular lymphoma that is intended to support an accelerated approval marketing application with the U.S. Food and Drug Administration.

Under the terms of the License Agreement, MEI will receive a $10 million upfront payment and is eligible to receive additional development and commercialization milestones totaling up to $87.5 million. MEI is also eligible to receive tiered double-digit royalties extending into the mid-teens. The agreement grants Kyowa Hakko Kirin exclusive rights to ME-401 to develop and commercialize ME-401 in Japan. The initial indication for development and regulatory approval under the agreement is relapsed or refractory follicular lymphoma.

"Kyowa Hakko Kirin is a well-regarded leader in the development and commercialization of hematology and oncology therapies in Japan," said David M. Urso., J.D., Chief Operating Officer of MEI Pharma. "This agreement is important for MEI as an opportunity to expand the development of ME-401 as a potential best-in-class PI3K delta inhibitor outside of the U.S. and is consistent with our strategy to optimize value through partnering opportunities abroad while developing capabilities for domestic commercialization."

"I am delighted to enter into an agreement with MEI Pharma for the development and commercialization of ME-401 in Japan," said Wataru Murata, Executive Officer, Director of Corporate Strategy & Planning Department. "We believe that ME-401 will be an important drug candidate in our oncology pipeline."

Kyowa Hakko Kirin plans to initiate a Phase 1 study in Japan in 2019.

About ME-401
ME-401 is an investigational oral phosphatidylinositol 3-kinase ("PI3K") delta inhibitor; PI3K delta is often overexpressed in cancer cells and plays a key role in the proliferation and survival of hematologic cancer cells. ME-401 displays high selectivity for the PI3K delta isoform and has distinct pharmaceutical properties from other PI3K delta inhibitors. It is being clinically evaluated in patients with various B-cell malignancies. MEI is initiating a Phase 2 study to evaluate the efficacy, safety, and tolerability of ME-401 as a single agent in patients with follicular lymphoma after failure of at least two prior systemic therapies including chemotherapy and an anti-CD20 antibody. The Phase 2 study is intended to support an accelerated approval marketing application with the U.S. Food and Drug Administration.

UCLB spinout Orchard Therapeutics announces closing of $225 million Initial Public Offering

On November 5, 2018 UCLB spinout Orchard Therapeutics, a biopharmaceutical company dedicated to transforming the lives of patients with serious and life-threatening rare diseases through autologous ex vivo gene therapies, reported the closing of its initial public offering of 16,103,572 American Depositary Shares ("ADSs"), each representing an ordinary share at an initial public offering price of $14.00 per share (Press release, UCLB, NOV 5, 2018, View Source [SID1234530722]). The gross proceeds from the offering were $225.5 million before deducting underwriting commissions and estimated offering expenses.

Orchard Therapeutics was founded in 2015, based on research arising from the groups of Prof. Bobby Gaspar and Prof. Adrian Thrasher, at the UCL Institute of Child Health.

Kura Oncology Reports Third Quarter 2018 Financial Results and Provides Corporate Update

On November 5, 2018 Kura Oncology, Inc., (Nasdaq: KURA) a clinical-stage biopharmaceutical company focused on the development of precision medicines for oncology, reported third quarter 2018 financial results and provided a corporate update (Press release, Kura Oncology, NOV 5, 2018, View Source [SID1234530721]).

"We are very encouraged by our growing body of data that support the potential of tipifarnib as a treatment for squamous cell carcinomas characterized by HRAS mutations," said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. "With our registration-directed trial of tipifarnib in HRAS mutant head and neck squamous cell carcinomas (HNSCC) now underway, we are focused on generating a data package to support an application for marketing approval in that indication, as we work to broaden the potential of tipifarnib in both HRAS mutant and non-HRAS mutant cancers. In that regard, we are encouraged by preliminary signals of clinical activity observed in patients with HRAS mutant SCCs as we believe this may represent a near-term opportunity to expand the use of tipifarnib into a broader set of HRAS mutant cancers."

"In addition," Dr. Wilson continued, "we believe the CXCL12 pathway also holds promise for identifying patients who will respond to tipifarnib, and we look forward to showing data next month at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting from our ongoing Phase 2 clinical trial in patients with peripheral T-cell lymphoma (PTCL) in which we are evaluating, on a prospective basis, the role of the CXCL12 pathway and markers of bone marrow homing as potential biomarkers of clinical activity of tipifarnib."

Corporate Update

Update on positive Phase 2 trial of tipifarnib in HRAS mutant HNSCC – In October 2018, Kura reported an update on its ongoing Phase 2 trial of tipifarnib in HRAS mutant HNSCC at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress. As of the September 7, 2018 clinical data cutoff date, tumor size reductions were observed in nine of 11 evaluable patients, with five confirmed partial responses (PRs), including three patients with durable responses lasting more than 17 months. A sixth patient achieved a confirmed PR after the data cutoff. Four patients had stable disease, including two patients who experienced prolonged disease stabilization lasting more than six months. Only one patient experienced progressive disease as best response.

Preliminary results from cohort of other HRAS mutant SCCs – Preliminary results from an additional cohort of patients with other HRAS mutant squamous cell carcinomas (SCCs) were also reported at ESMO (Free ESMO Whitepaper). One of the two evaluable patients in this cohort achieved a confirmed PR and the other patient achieved prolonged disease stabilization lasting more than eight months. Four patients were not evaluable as of the data cutoff date, including two patients who were pending initial efficacy assessments.

Significant association observed between allele frequency and clinical benefit – An analysis of available tumor biopsy samples from patients in Kura’s ongoing Phase 2 trial in HNSCC/SCC cancers revealed a significant association between the allele frequency of HRAS mutations and clinical benefit. Of the 13 HNSCC and SCC patients with a tumor HRAS mutant allele frequency greater than 20%, six achieved PRs, one achieved an unconfirmed PR and two experienced disease stabilization greater than six months. No meaningful clinical benefit was observed in the seven patients with an allele frequency less than 20%. Based on these observations, Kura has introduced a minimum HRAS mutant allele frequency of 20% as an entry criterion in its registration-directed trial of tipifarnib in HRAS mutant HNSCC and is working to implement the same entry criterion in its ongoing Phase 2 study of tipifarnib in HRAS mutant SCCs.

Initiation of registration-directed trial of tipifarnib in HRAS mutant HNSCC – Earlier today, Kura announced that its registration-directed trial of tipifarnib in HRAS mutant HNSCC has been initiated and is open for enrollment. The global, multi-center trial has two cohorts: SEQ-HN, a non-interventional screening and outcomes cohort, and AIM-HN, a treatment cohort. AIM-HN is designed to enroll at least 59 patients with HRAS mutant HNSCC who have received prior platinum-based therapy. AIM-HN is expected to take approximately two years to fully enroll, with objective response rate as the primary endpoint. Based on feedback from the U.S. Food and Drug Administration, Kura believes that the trial, if positive, could support an application for accelerated approval.

Preliminary data from expansion cohorts in Phase 2 trial of tipifarnib in PTCL at ASH (Free ASH Whitepaper) – Kura is evaluating, on a prospective basis, the role of the CXCL12 pathway and markers of bone marrow homing as potential biomarkers of clinical activity for tipifarnib in various hematologic malignancies. The Company’s ongoing Phase 2 PTCL trial was the first of the three to begin and is actively enrolling patients into two cohorts: 1) patients with angioimmunoblastic T-cell lymphoma (AITL) and 2) patients with PTCL who have the absence of a single nucleotide variation in the 3’ untranslated region of the CXCL12 gene. Kura expects to provide preliminary data from these cohorts at ASH (Free ASH Whitepaper) in December 2018.
Financial Results

Research and development expenses for the third quarter of 2018 were $11.7 million, compared to $7.1 million for the third quarter of 2017.

General and administrative expenses for the third quarter of 2018 were $4.3 million, compared to $2.4 million for the third quarter of 2017.

Net loss for the third quarter of 2018 was $15.0 million, or $0.40 per share, compared to $9.3 million, or $0.38 per share, for the third quarter of 2017.

Cash, cash equivalents and short-term investments totaled $187.4 million as of September 30, 2018, compared with $93.1 million as of December 31, 2017.
Upcoming Milestones

Preliminary data from AITL and CXCL12+ cohorts in Phase 2 trial of tipifarnib in PTCL at ASH (Free ASH Whitepaper)

Additional biomarker-enriched data from other hematologic indications in 2019

Additional data from Phase 2 trial of tipifarnib in HRAS mutant SCC in 2019

Data from Phase 1 dose-escalation trial of ERK inhibitor KO-947 in 2019

Submission of an investigational new drug application for menin-MLL inhibitor KO-539 in first quarter of 2019
Conference Call and Webcast

Kura’s management will host a webcast and conference call today at 4:30 p.m. ET / 1:30 p.m. PT today, November 5, 2018, to discuss the financial results for the third quarter of 2018 and provide a corporate update. The live call may be accessed by dialing (877) 516-3514 for domestic callers and (281) 973-6129 for international callers and entering the conference code: 6593979. A live webcast of the call will be available from the Investors and Media section of the Company’s website at www.kuraoncology.com, and will be archived there for 30 days.