The second-most advanced investigational drug in MEI Pharma’s four-asset portfolio is drawing attention from overseas as a potential treatment for several leukemias and lymphomas.
Japanese life sciences company Kyowa Hakko Kirin has agreed to pay the San Diego company $10 million upfront for rights to develop and commercialize ME-401 in Japan. The Japanese company will pay MEI up to $87.5 million more if the drug, a PI3K delta inhibitor, meets a variety of milestones; plus royalties from sales if it reaches the market.
Targeted therapies with PI3K inhibitors aren’t new. But such compounds can cause side effects, including diarrhea, colitis, and pneumonia, that limit how long a patient can receive such drugs.
MEI president and CEO Dan Gold, however, says the pharmaceutical properties of ME-401 set it apart from competitors—–and that the drug may provoke fewer side effects while remaining effective through an intermittent, rather than continuous, dosing schedule of one week one, three weeks off. The company is planning a Phase 2 trial soon to evaluate such a schedule in patients with whose follicular lymphoma (FL) has relapsed or has not responded to earlier treatment.
Gold joined MEI in 2010 when the company relocated to San Diego from Australia. MEI acquired ME-401 (formerly PWT143) from San Francisco’s Pathway Therapeutics in 2013.
“Doctors are not excited to use (PI3K), especially in healthier patients,” Gold said. “If we can show that this intermittent schedule really solves the toxicity problem without sacrificing the activity, then we open the door to lots of interesting potential to expand our market.”
For years researchers have been studying immunotherapies—which essentially enable the body’s immune system to more effectively fight cancer—as potential alternatives or complements to chemotherapy.
Recently the FDA approved cemiplimab (Libtayo), a checkpoint inhibitor from Regeneron (NASDAQ: REGN) and Sanofi (NYSE: SNY). The drug is a checkpoint inhibitor, a type of cancer drug that blocks a tumor’s ability to hide from the immune system, and it’s the seventh one to receive approval from the agency. Shortly thereafter, the scientists credited with discovering checkpoint inhibition—James Allison of MD Anderson Cancer Center in Houston and Tasuku Honjo of Kyoto University in Japan—won this year’s Nobel Prize in physiology or medicine.
Around the time MEI acquired the rights to ME-401, companies were racing to develop inhibitors to target B cells.
Foster City, CA-based Gilead Sciences (NASDAQ: GILD) was the first to market with a PI3K drug, idelalisib (Zydelig) in 2014.
But Sunnyvale, CA-based Pharmacyclics and Johnson & Johnson (NYSE: JNJ) got the OK for ibrutinib (Imbruvica), a Btk inhibitor, in 2013, and AbbVie (NYSE: ticker[[ABBV]]) later bought Pharmacyclics—and ibrutinib—for $21 billion.
“When all was said and done, Pharmacyclics…won the race,” Gold said. “They didn’t win it so much on efficacy, because in fact the biology tells us that PI3 delta should be a superior target for B-cell malignancies. The problem was that the PI3 delta class had toxicities which made the Btk (class) much more attractive as therapeutics because their toxicity profile is much, much better.”
However, interest in PI3K seems to be undergoing a rebirth of sorts. Bayer’s copanlisib (Aliqopa), an intravenous option for patients with relapsed FL who had received at least two prior treatments, was approved about a year ago.
And Verastem’s duvelisib (Copiktra), a twice daily pill, was approved in September for patients whose FL or chronic lymphocytic lymphoma (CLL) has relapsed or has not responded to at least two prior treatments.
In June MEI reported data from an ongoing Phase 1b study of ME-401. In the 30-patient study, the once daily drug demonstrated a 90 percent response rate in those with FL, CLL and small lymphocytic lymphoma (SLL).
The results led to a $75 million investment, a private placement led by Vivo Capital and CAM Capital, slated to fund ME-401’s continued clinical development. New Enterprise Associates, Perceptive Advisors, the Biotechnology Value Fund, Boxer Capital of Tavistock Group, and Amzak Health also participated, as did other new and earlier investors, MEI Pharma said at the time.
As part of the trial, MEI Pharma is also testing ME-401 in combination with rituximab. (Nicknamed ‘Vitamin R’ because of its broad utility, rituximab—the first biotech drug approved for cancer—was invented by the former Idec Pharmaceuticals, now part of Cambridge, Mass.-based Biogen.)
A few weeks prior to today’s announcement, MEI Pharma announced a collaboration with Chinese biopharma BeiGene (NASDAQ: BGN) to test how patients would respond to a combination of ME-401 and BeiGene’s zanubrutinib, an investigational BTK inhibitor.
“There are published data that suggests that if you could interfere with the Btk pathway and the delta pathway you may actually get better responses than either of those agents independently,” Gold said.
At the time, Oppenheimer analyst Leah Rush Cann said in a research note that data from the collaboration with BeiGene—and the ongoing trial testing a rituximab combo, too—could expand ME-401’s potential use. The firm anticipates the drug will launch in 2022, and estimates sales of about $620 million by the following year.
MEI signed a similar deal in 2016 for pracinostat, another one of its investigational drugs. Swiss pharmaceutical group Helsinn has paid MEI $20 million to date; an additional $444 million is tied to regulatory and sales-based milestones for the drug, which is being evaluated in a Phase 3 trial for patients who are diagnosed with acute myeloid leukemia (AML) who are unfit to receive intensive chemotherapy.
This latest news from MEI Pharma comes a month before the annual American Society of Hematology (ASH) conference, taking place this year in San Diego. There, the company plans to present data from the Phase 1B trial as well as others in its pipeline.