Mateon Therapeutics (NASDAQ:MATN) is developing vascular disrupting agents (VDAs) that selectively disrupt abnormal tumor blood vessels, which supply nutrients to cancer cells, with an initial clinical focus on platinum-resistant ovarian cancer and acute myeloid leukemia.
“VDAs have been around for a long time but we’re taking them in a new direction: in combination with anti-angiogenic (AA) therapies,” president and CEO, Dr. William Schwieterman, says in an interview with BioTuesdays.com.
There are at least 12 AA drugs approved in the U.S. for some 15 different oncology indications, with estimated sales in 2015 exceeding $10-billion.
Dr. Schwieterman explains that VDAs lead to the death of interior tumor cells, but may spare some tumor cells on the outer rim of the tumor. These residual rim cells can tap into surrounding blood supply and regenerate tumor cells via angiogenesis. Combination treatment with VDAs and an angiogenesis inhibitor, like Avastin, is intended to kill the interior tumor cells and prevent growth of new blood vessels, which can supply nutrients to tumor cells.
“Combining VDAs and AAs has been shown to destroy blood vessels in the interior of the tumor while preventing the formation of new tumor blood vessels,” he adds. “Preclinical and initial clinical data support the therapeutic potential of utilizing VDAs combined with AAs in a range of tumor types.”
Dr. Schwieterman joined Mateon in May 2015 when the company was known as OXiGENE. His track record includes a 10-year stint with the FDA’s Center for Biologics Evaluation Research, where he reviewed hundreds of agents across several therapeutic areas.
He says Mateon’s lead product, CA4P, is currently being developed to treat platinum-resistant ovarian cancer. It has treated more than 475 patients, with its greatest activity in combination with AA agents. The drug candidate has received orphan drug status in the U.S. and EU.
“We think we have a very good understanding of the safety of CA4P based on an earlier Phase 2 study in non-small cell lung cancer,” he adds.
In 2014, the Gynecologic Oncology Group (GOG) concluded a Phase 2 open-label trial of CA4P plus Avastin, compared with Avastin alone, in 107 women with recurrent ovarian cancer. The GOG is part of the NIH under the Cancer Therapy Evaluation Program. Avastin has been approved by the FDA for platinum-resistant ovarian cancer.
While the combination of the two drugs successfully enhanced progression-free survival, the GOG-01861 study didn't yield a statistically significant difference in overall survival to make a case for CA4P’s approval. The data was published in the peer-reviewed Journal of Clinical Oncology earlier this year.
“I joined Mateon in 2015 because the results of this study validated what had been seen in earlier studies and I thought we could build on that,” Dr. Schwieterman points out.
In mid-2016, Mateon presented new analyses from a more recent and more mature dataset from the GOG-0186I study, including analyses to further define the patient population most likely to benefit from treatment with CA4P.
Given the preclinical data and the mechanism of action of CA4P, Mateon suggested that CA4P is likely to have the greatest effect in women with “measurable disease” and on those with larger tumors in platinum-resistant ovarian cancer. The new analyses showed an improvement of 5.6 months in overall survival and 3.7 months in progression-free survival in women with measurable disease.
Rodman & Renshaw analyst Raghuram Selvaraju, who assumed coverage of Mateon last month, said existing clinical data supports the notion that CA4P provides a “consolidated benefit over the current standard-of-care in platinum-resistant ovarian cancer.”
He rates Mateon a “buy” with a price target of $2. The stock closed at $0.68 on Friday. “We believe Mateon represents an underrated prospect with significant upside potential for the long-term investor,” he added.
In the summer, Mateon began enrolling women with platinum-resistant ovarian cancer in a Phase 2/3 study, called FOCUS, to test CA4P plus Avastin plus chemotherapy, effectively combining a VDA with products with complementary mechanisms of actions, against placebo plus Avastin plus chemotherapy.
The trial’s adaptive design, includes an 80-patient Phase 2 randomized controlled arm, at sites mostly in the U.S., moving into a 356-patient Phase 3 double-blind confirmatory study of the efficacy of the triple drug regimen at sites around the world.
Dr. Schwieterman says the Phase 3 study will be triggered based on interim analyses of the Phase 2 portion to detect efficacy and test powering assumptions for a Phase 3 trial. There will be Phase 2 interim analyses in each quarter next year, with the Phase 2 trial concluding at the end of 2017. “At that point, we’ll know if this regimen is superior to the current standard-of-care,” he adds.
CA4P is also being studied in combination with Votrient in an on-going Phase 1b/2 clinical trial, called PAZOFOS, in recurrent ovarian cancer, which is sponsored by the Christie Hospital NHS Foundation Trust in the U.K. The study will read out in 2018.
The company’s second VDA candidate, OXi4503, is being studied in combination with cytarabine in a Phase 1/2 trial in relapsed or refractory acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). OXi4503 has received orphan drug status in AML in the U.S. and EU.
Earlier this year, Mateon completed enrollment of the first cohort of patients and initiated the second cohort in OX1222, an open-label dose ranging study of OXi4503 in combination with cytarabine, in patients with relapsed/refractory AML.
Dr. Schwieterman says interim data from OX1222 has been submitted for a poster presentation at the ASH meeting in San Diego in December. “We’ll advance to Phase 2 if sufficient efficacy is observed and seek a partner to conduct a large randomized trial.”