Bayer, Loxo Oncology to Develop, Commercialize Therapies for Genetic Drivers of Cancer

Bayer has entered into an exclusive global collaboration with Loxo Oncology for the development and commercialization of larotrectinib (LOXO-101) and LOXO-195. Both compounds are being investigated in global studies for the treatment of patients with cancers harboring tropomyosin receptor kinase (TRK) gene fusions, which are genetic alterations across a wide range of tumors resulting in uncontrolled TRK signaling and tumor growth.

"Bayer has a long-standing commitment to cancer research, with the goal of focusing on the advances in science that will make a real difference in patients' lives," said Carsten Brunn, head of Pharmaceuticals, Americas Region at Bayer.  "Our new partnership with Loxo Oncology complements our existing portfolio and pipeline, and we are proud to continue to be at the forefront of the next wave of innovation in oncology with the addition of these exciting compounds."

Larotrectinib is an investigational oral, selective TRK inhibitor. LOXO-195 is an investigational next-generation, selective TRK inhibitor capable of addressing potential mechanisms of acquired resistance that may emerge in patients receiving larotrectinib or multikinase inhibitors with anti-TRK activity. Larotrectinib is currently the only selective TRK inhibitor in clinical development with the comprised clinical data set showing an overall response rate of 75 percent, confirmed by an independent review committee, regardless of tumor type and age. The most common treatment-emergent adverse events, regardless of relationship to larotrectinib, included fatigue, dizziness, nausea, and anemia, all largely grade 1/2 events. The first filing for larotrectinib is planned in the U.S. in late 2017 or early 2018, with the EU filing expected in 2018.

Under the terms of the agreement, Loxo Oncology will receive an upfront payment of USD 400 million and is eligible for USD 450 million in milestone payments upon larotrectinib regulatory approvals and first commercial sale events in certain major markets and an additional USD 200 million in milestones payments upon LOXO-195 regulatory approvals and first commercial sale events in certain major markets.  Bayer and Loxo Oncology will jointly develop the two products, larotrectinib and LOXO-195, and share development costs on a 50/50 basis. Bayer will lead ex-U.S. regulatory activities, and worldwide commercial activities. In the U.S., where Bayer and Loxo Oncology will co-promote the products, the parties will share commercial costs and profits on a 50/50 basis. Loxo Oncology will remain responsible for the filing in the U.S.  Bayer will pay Loxo Oncology tiered double-digit percentage royalties on future net sales outside of the U.S., and U.S. and ex-U.S. sales milestones totaling USD 500 million.

Larotrectinib (LOXO-101) is an oral and selective investigational new drug in clinical development for the treatment of patients across a wide range of cancers that harbor abnormalities involving the tropomyosin receptor kinases (TRKs). Growing research suggests that the NTRK genes, which encode for TRKs, can become abnormally fused to other genes, resulting in growth signals that can lead to cancer in many sites of the body.

In an analysis of 55 RECIST-evaluable TRK fusion adult and pediatric patients, larotrectinib demonstrated a 75 percent (95% CI: 61-85%) independently-reviewed confirmed overall response rate (ORR) and an 80 percent (95% CI: 67-90%) investigator-assessed confirmed ORR, across many different types of solid tumors. Larotrectinib received orphan drug designation in the US for the treatment of solid tumors harboring NTRK-fusion proteins and in Europe for soft tissue sarcoma. Additionally, the FDA granted breakthrough therapy designation to larotrectinib for the treatment of unresectable or metastatic solid tumors with NTRK-fusion proteins in adult and pediatric patients who require systemic therapy and who have either progressed following prior treatment or who have no acceptable alternative treatments.

LOXO-195 is an oral and selective investigational new drug in clinical development for the treatment of patients with cancers that have acquired resistance to initial TRK therapy such as larotrectinib. Though drugs such as larotrectinib can induce durable responses in these patients, the cancer may eventually begin to grow again. This phenomenon is called "acquired resistance," in that the cancer has acquired features conferring resistance to the initial therapy that was once effective. Emerging data in the field of TRK inhibition suggest that acquired resistance may emerge due to TRK kinase point mutations. LOXO-195 was designed to address these new point mutations and induce a new response in the patient's cancer. In July 2017, a multi-center Phase I/II trial in patients with TRK fusion cancers who have progressed while receiving another TRK inhibitor or are intolerant to another TRK inhibitor was initiated.