Arriving at MEI Pharma Inc.’s deal with Kyowa Kirin Co. Ltd., focused on phase II-stage ME-401 for B-cell malignancies, was a competitive process that brought large and midsized pharma bidders to the table, MEI Chief Operating Officer David Urso said, but the terms proposed by suitors tended to “look a lot the same.” Kyowa’s offer of more flexibility for MEI carried the day. “We're going to be much more involved in the commercialization of this asset, and that was a key driver for us in selecting a partner,” he said.

The arrangement means $100 million up front for San Diego-based MEI, which could bank up to $582.5 million more if development, regulatory and commercial goals are reached. Shares of the firm (NASDAQ:MEIP) closed at $2.50, up 83 cents or 50%, after trading as high as $3.64. MEI and Kirin, of Tokyo, will co-develop and co-promote ME-401 in the U.S. on a 50-50 profit and cost basis.

An oral, once-daily therapy selective for phosphatidylinositol 3-kinase (PI3K) delta, ME-401 gained fast-track designation from the FDA and is undergoing two studies. One is a phase II effort as a monotherapy for the treatment of adults with relapsed or refractory follicular lymphoma (FL) after failure of at least two prior systemic therapies, including chemotherapy and an anti-CD20 antibody. If results are good, MEI plans to ask for accelerated approval. The second trial is a multi-arm, open-label, phase Ib dose-escalation and expansion bid testing ME-401 as a monotherapy and in combination with other therapies or investigational agents in patients with relapsed or refractory B-cell malignancies. A phase I experiment was started by Kirin last year, evaluating the drug as a monotherapy in patients with indolent B-cell malignancy in Japan.

CEO Daniel Gold told investors during a conference call that MEI “jumped into action” when the COVID-19 crisis surfaced. “We wanted to ensure, first and foremost, that those patients who are already being treated would be able to continue to be treated,” he said. “We proactively put a lot of efforts into this. We contacted every investigator with a series of protocols that we had worked out in accordance with regulatory agencies to ensure the safety of those patients and their ability to continue. Thankfully, I can tell you that, to date, there has been no impact [from COVID-19] in terms of the patients who are already enrolled. They continue to receive their drug.” New patients “continue to enroll remarkably,” he added. “We are open in at least 93 sites around the world. Patients [who] are eligible after screening are going on drug,” though “the pace at which that's happening is probably slower than it was prior. It's hard to know what the overall impact in terms of our timeline is going to be.”

An update on ME-401 is expected at the American Society of Clinical Oncology meeting in late May and early June 2020.

The drug came to MEI in September 2013 by way of San Francisco-based Pathway Therapeutics Inc. for an up-front amount and no obligations to milestone payments or royalties. Then at the preclinical stage and known as PWT-143, ME-401 since has made good on its promise in a class that’s well known and characterized – and still fairly busy, despite tolerability problems that have dogged PI3K candidates. Gilead Sciences Inc., of Foster City, Calif., ran into trial death woes with Zydelig (idelalisib), although in the summer of 2014, the drug gained approval. It’s indicated for patients whose chronic lymphocytic leukemia has relapsed. Used in combination with Rituxan (rituximab, Roche Holding AG/Biogen Inc.), Zydelig gained clearance in patients for whom Rituxan alone would be considered appropriate therapy due to co-morbidities. The green light also came on an accelerated basis to treat patients with relapsed FL and relapsed small lymphocytic lymphoma.

TG, Kazia headliners in PI3K

“MEI-401 is likely the most powerful drug in the PI3K delta class, and MEI has labored mightily to figure out how to use it safely,” BTIG analyst Thomas Shrader noted in a report. “Today's news seems to underscore the basic trend in oncology that efficacy trumps most other factors as supportive care improves.” Although progress has been made in FL with antibody-drug conjugates and bispecific monoclonal antibodies, leading to “an increasingly competitive market, the disease remains without a true cure and PI3K delta inhibitors will likely have meaningful opportunities to improve on current standard of care,” he wrote.

MEI CEO Gold said Kirin “has done a phenomenal job in launching their own internally developed treatment for T-cell lymphoma, which is an antibody that they developed and got worldwide or, at least, European, U.S. and Japanese approvals already, and have launched in those territories.” Sales, he added, are “doing very well.” In August 2018, Kirin won FDA approval for Poteligeo (mogamulizumab-kpkc) to treat adult patients with relapsed or refractory mycosis fungoides or Sézary syndrome – two subtypes of cutaneous T-cell lymphoma – after at least one prior systemic therapy. It’s a monoclonal antibody targeting CC chemokine receptor 4.

A recent win in PI3K was scored by Sydney-based Kazia Therapeutics Ltd., which reported interim data showing that lead candidate paxalisib (formerly GDC-0084) saw a positive overall survival (OS) signal in its phase II glioblastoma trial, and the company raised AU$7.2 million (then US$4.4 million) days after the data were released. Results from the first nine patients of the escalation cohort showed median OS of 17.7 months compared to 12.7 months associated with the standard of care, temozolomide. Progression-free survival (PFS) of all 30 patients reached 8.5 months compared to 5.3 months for temozolomide. In November 2019, Kazia reported interim findings that showed a PFS rate of 8.4 months.

Another player of interest: New York-based TG Therapeutics Inc., which recently chalked a phase IIb victory in the FL cohort of the Unity-NHL pivotal experiment testing the once-daily PI3K delta inhibitor umbralisib. The drug met the primary endpoint of overall response rate (ORR) in the FL cohort as determined by independent review committee for all treated patients (n=118) given at least two prior lines of therapy, including an anti-CD20 monoclonal antibody and an alkylating agent. Results hit the company's prespecified ORR target of 40% to 50%, and umbralisib was well-tolerated, with a safety profile consistent with previous experiments. The FDA has granted orphan drug designation to the compound in FL. Umbralisib is being evaluated across several types of lymphoma in the Unity-NHL effort.

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