Bayer to obtain full rights to global development and commercialization of oncology compounds Vitrakvi® (larotrectinib) and BAY 2731954 (LOXO-195)

-- Bayer exercised its option to obtain full licensing rights for the two TRK inhibitor agents under a change-in-control clause in its agreement with Loxo Oncology

-- Bayer to be solely responsible for the global development and commercialization of both Vitrakvi® and BAY 2731954 (LOXO-195)

-- Co-promotion of Vitrakvi® in the U.S. to be converted into exclusive commercialization by Bayer

-- Vitrakvi® was approved in November 2018 as the first TRK inhibitor for patients with advanced solid tumors harboring an NTRK gene fusion; filings in Europe and other regions underway

News provided by

Bayer

Feb 15, 2019, 09:35 ET

WHIPPANY, N.J., Feb. 15, 2019 /PRNewswire/ -- Bayer has exercised its option, under a change-in-control clause in the collaboration agreement with Loxo Oncology, to obtain the exclusive licensing rights for the global development and commercialization, for Vitrakvi® (larotrectinib) and BAY 2731954 (LOXO-195). Both compounds are being developed globally for the treatment of adult and pediatric patients with advanced solid tumors harboring NTRK gene fusions. The option was triggered by the acquisition of Loxo Oncology by Eli Lilly and Company, which became effective today. As a result of this exercise, the joint co-promotion agreement in the U.S. between Bayer and Loxo Oncology is being converted to full commercialization in the U.S. by Bayer.

"Bayer is dedicated to improving the lives of cancer patients, and precision oncology is a promising area that has the potential to redefine the way cancer patients are treated. Our collaboration with Loxo Oncology was an important milestone and with the opportunity to exercise our option on Vitrakvi^® and BAY 2731954, we are taking the next step in our efforts to advance the future of cancer care and strengthen our leadership in this field," said Robert LaCaze, Member of the Executive Committee of Bayer's Pharmaceuticals Division and Head of the Oncology Strategic Business Unit at Bayer. "With the first-ever approved TRK inhibitor with activity against TRKA, TRKB and TRKC, Vitrakvi^®, and BAY 2731954 progressing through clinical development, we have two compounds in our precision oncology portfolio and we are committed to expanding this portfolio by bringing forward highly differentiated and promising additional projects."

In November 2017, Bayer and Loxo Oncology entered into a global collaboration for the joint development and commercialization of the TRK inhibitors Vitrakvi^® and BAY 2731954 (LOXO-195). Following the change of control, Bayer will be solely responsible for the global development and commercialization of both Vitrakvi^® and BAY 2731954. Bayer is already leading ex-U.S. regulatory activities, and worldwide commercial activities. When the new exclusive licensing arrangement takes effect, the co-promotion in the U.S. will be converted into an exclusive commercialization by Bayer and the sharing of commercial costs and profits on a 50/50 basis for the U.S. market will be replaced by royalties to be paid by Bayer. Bayer will continue to pay royalties on future net sales outside the U.S.

In addition, in connection with Bayer's exercise of the option, certain licenses granted by Loxo Oncology to Bayer will become exclusive following anti-trust clearance in the U.S.

About Vitrakvi^® (larotrectinib) and BAY 2731954
Vitrakvi^® is an oral TRK inhibitor for the treatment of adult and pediatric patients with solid tumors with an NTRK gene fusion without a known acquired resistance mutation that are either metastatic or where surgical resection will likely result in severe morbidity, and have no satisfactory alternative treatments or have progressed following treatment. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Research suggests that the NTRK genes can become abnormally fused to other genes, producing a TRK fusion protein that can act as an oncogenic driver, leading to cancer cell growth and survival.

BAY 2731954 is an oral investigational new drug in clinical development rationally designed for the treatment of patients with cancers that have acquired resistance to initial TRK therapy. 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.

About TRK Fusion Cancer
TRK fusion cancer occurs when an NTRK gene fuses with another unrelated gene, producing an altered TRK protein. The altered protein, or TRK fusion protein, becomes constitutively active or overexpressed, triggering a signaling cascade. These TRK fusion proteins act as oncogenic drivers promoting cell growth and survival, leading to TRK fusion cancer, regardless of where it originates in the body. TRK fusion cancer is not limited to certain types of tissues and can occur in any part of the body. TRK fusion cancer occurs in various adult and pediatric solid tumors with varying frequency, including lung, thyroid, GI cancers (colon, cholangiocarcinoma, pancreatic and appendiceal), sarcoma, CNS cancers (glioma and glioblastoma), salivary gland cancers (mammary analogue secretory carcinoma) and pediatric cancers (infantile fibrosarcoma and soft tissue sarcoma).

Important Safety Information

Neurotoxicity: Among the 176 patients who received VITRAKVI, neurologic adverse reactions of any grade occurred in 53% of patients, including Grade 3 and Grade 4 neurologic adverse reactions in 6% and 0.6% of patients, respectively. The majority (65%) of neurological adverse reactions occurred within the first three months of treatment (range 1 day to 2.2 years). Grade 3 neurologic adverse reactions included delirium (2%), dysarthria (1%), dizziness (1%), gait disturbance (1%), and paresthesia (1%). Grade 4 encephalopathy (0.6%) occurred in a single patient. Neurologic adverse reactions leading to dose modification included dizziness (3%), gait disturbance (1%), delirium (1%), memory impairment (1%), and tremor (1%).

Advise patients and caretakers of these risks with VITRAKVI. Advise patients not to drive or operate hazardous machinery if they are experiencing neurologic adverse reactions. Withhold or permanently discontinue VITRAKVI based on the severity. If withheld, modify the VITRAKVI dose when resumed.

Hepatotoxicity: Among the 176 patients who received VITRAKVI, increased transaminases of any grade occurred in 45%, including Grade 3 increased AST or ALT in 6% of patients. One patient (0.6%) experienced Grade 4 increased ALT. The median time to onset of increased AST was 2 months (range: 1 month to 2.6 years). The median time to onset of increased ALT was 2 months (range: 1 month to 1.1 years). Increased AST and ALT leading to dose modifications occurred in 4% and 6% of patients, respectively. Increased AST or ALT led to permanent discontinuation in 2% of patients.

Monitor liver tests, including ALT and AST, every 2 weeks during the first month of treatment, then monthly thereafter, and as clinically indicated. Withhold or permanently discontinue VITRAKVI based on the severity. If withheld, modify the VITRAKVI dosage when resumed.

Embryo-Fetal Toxicity: VITRAKVI can cause fetal harm when administered to a pregnant woman. Larotrectinib resulted in malformations in rats and rabbits at maternal exposures that were approximately 11- and 0.7-times, respectively, those observed at the clinical dose of 100 mg twice daily

Advise women of the potential risk to a fetus. Advise females of reproductive potential to use an effective method of contraception during treatment and for 1 week after the final dose of VITRAKVI.

Most Common Adverse Reactions (≥20%): The most common adverse reactions (≥20%) were:
increased ALT (45%), increased AST (45%), anemia (42%), fatigue (37%), nausea (29%), dizziness (28%), cough (26%), vomiting (26%), constipation (23%), and diarrhea (22%).

Drug Interactions: Avoid coadministration of VITRAKVI with strong CYP3A4 inhibitors (including grapefruit or grapefruit juice), strong CYP3A4 inducers (including St. John's wort), or sensitive CYP3A4 substrates. If coadministration of strong CYP3A4 inhibitors or inducers cannot be avoided, modify the VITRAKVI dose as recommended. If coadministration of sensitive CYP3A4 substrates cannot be avoided, monitor patients for increased adverse reactions of these drugs.

Lactation: Advise women not to breastfeed during treatment with VITRAKVI and for 1 week after the final dose.

Please see the full Prescribing Information.

About Oncology at Bayer
Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The oncology franchise at Bayer includes five marketed products and several other compounds in various stages of clinical development. Together, these products reflect the company's approach to research, which prioritizes targets and pathways with the potential to impact the way that cancer is treated.

About Bayer
Bayer is a global enterprise with core competencies in the Life Science fields of health care and agriculture. Its products and services are designed to benefit people and improve their quality of life. At the same time, the Group aims to create value through innovation, growth and high earning power. Bayer is committed to the principles of sustainable development and to its social and ethical responsibilities as a corporate citizen. In fiscal 2017, the Group employed around 99,800 people and had sales of EUR 35.0 billion. Capital expenditures amounted to EUR 2.4 billion, R&D expenses to EUR 4.5 billion. For more information, go to www.bayer.us.

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Forward-Looking Statements
This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer's public reports which are available on the Bayer website at www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

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