Mirati Therapeutics Announces Positive Results in Immuno-Oncology Combination Trials

Mirati Therapeutics, Inc. (Nasdaq: MRTX) (the Company or Mirati), On 4/24/18 provided a progress update on its lead development programs and announced updated, positive clinical trial data for sitravatinib, a spectrum selective kinase inhibitor, and mocetinostat, a class I and IV HDAC inhibitor. The Company has been evaluating sitravatinib and mocetinostat in separate Phase 2 clinical trials in combination with checkpoint inhibitor therapy in non-small cell lung cancer (NSCLC) patients whose disease had progressed following prior treatment with a checkpoint inhibitor. Both clinical trials have generated encouraging preliminary data demonstrating the potential to overcome resistance to checkpoint inhibitor therapy.

"The majority of NSCLC patients either do not respond to checkpoint inhibitor therapy or experience disease progression following treatment. These patients have limited treatment options and generally experience poor outcomes in response to standard of care chemotherapy," said Charles M. Baum, M.D., Ph.D., President and Chief Executive Officer. "The preliminary data from our Phase 2 study of sitravatinib plus nivolumab continue to highlight the promise of this combination to overcome resistance to initial checkpoint inhibitor therapy and provide a meaningful treatment option for this large and underserved patient population."

Sitravatinib is being evaluated in a Phase 2 study in combination with nivolumab (Opdivo), an anti-PD-1 checkpoint inhibitor, in patients with NSCLC who have experienced documented disease progression following prior treatment with a checkpoint inhibitor. As of the data cutoff date of March 31, 2018:

• 23 patients were evaluable for response with at least one radiographic scan
• Six patients achieved a Partial Response (PR) (four confirmed and two unconfirmed)
• Five of the six patients with PRs remain on study, including both patients with unconfirmed PRs; the longest treatment duration exceeds 50 weeks and is ongoing
• The other patient with a PR progressed following a treatment duration that exceeded 40 weeks
• 19 of 23 patients demonstrated tumor reductions
• To date, the combination has been well-tolerated and most adverse events (AEs) reported by investigators were Grade 1 or 2.

In a separate Phase 2 study, mocetinostat is being evaluated in combination with durvalumab (IMFINZI®), an anti-PD-L1 checkpoint inhibitor, in patients with NSCLC who have experienced documented disease progression following prior treatment with a checkpoint inhibitor. As of the data cutoff date of March 31, 2018:

• 23 patients were evaluable for response with at least one radiographic scan
• Three patients achieved a PR (two confirmed and one unconfirmed)
• All three patients with PRs remain on study; the longest treatment duration exceeds 44 weeks and is ongoing
• 8 of 23 patients demonstrated tumor reductions
• To date, the combination has been well-tolerated, and most AEs reported by investigators were Grade 1 or 2.
• 31 patients have been enrolled in this ongoing trial and the Company plans to present more mature data at an oncology conference later this year.

MRTX849 is an orally-available small molecule that potently and selectively inhibits a form of KRAS which harbors a substitution mutation (G12C). KRAS G12C mutations are present in approximately 14% of NSCLC adenocarcinoma patients and 5% of colorectal cancer patients.  Tumors characterized by KRAS G12C mutations are commonly associated with poor prognosis and resistance to therapy, and patients with these mutations have few treatment options. MTRX849 has demonstrated complete regression of KRAS G12C-positive human tumors implanted in mice. IND-enabling preclinical studies are underway, and an IND submission is expected in the fourth quarter of 2018, with early clinical proof-of-concept anticipated in 2019.