– Designation Represents Positive Progress for a Unique Patient Population in Need of Targeted Therapy Options

CAMBRIDGE, Mass. & OSAKA, Japan--(BUSINESS WIRE)--Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) (“Takeda”) today announced that the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation for its investigational drug mobocertinib (TAK-788) for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy. There are currently no approved therapies designed to treat this specific form of NSCLC. Mobocertinib is a small-molecule tyrosine kinase inhibitor (TKI) designed to selectively target EGFR and human EGFR 2 (HER2) exon 20 insertion mutations.

The Breakthrough Therapy Designation is based on the overall response rate (ORR) and the long-term benefit seen in patients who responded in a Phase 1/2 study evaluating the safety and efficacy of mobocertinib in patients with locally advanced or metastatic NSCLC whose tumors harbor EGFR exon 20 insertion mutations and have been previously treated with systemic chemotherapy. This signals a potential advancement in addressing the needs of patients for whom no targeted therapies exist and current treatment options provide limited benefit.

“We are pleased that the FDA has recognized the therapeutic potential mobocertinib offers for patients with EGFR exon 20 insertion-mutant NSCLC who are desperately in need of effective treatment options,” said Christopher Arendt, Head, Oncology Therapeutic Area Unit, Takeda. “At Takeda, we are committed to developing novel medicines for hard-to-treat diseases. Establishing Breakthrough Therapy Designation for mobocertinib is one step forward in our efforts to help change the current standard of care for this underserved population.”

“Although most EGFR mutations can be targeted by currently available TKIs, people with exon 20 insertion mutations often suffer and feel forgotten since available EGFR inhibitors don’t work well in their cancer,” said Jill Feldman, Lung Cancer Patient, Advocate, and Co-Founder of the EGFR Resisters. “We are excited by the potential this treatment has to extend the lives of people who have had no approved treatment options to target their disease.”

Breakthrough Therapy Designation from the U.S. FDA is granted to accelerate the development and regulatory review of investigational drugs that are intended to treat serious or life-threatening ailments. Agents with this designation have shown preliminary clinical evidence that indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.

Takeda will present for the first time the development of mobocertinib, including the first public disclosure of the structure, during the American Association for Cancer Research (AACR) Virtual Annual Meeting I in a New Drugs on the Horizon session on Tuesday, April 28, from 11:14-11:34 a.m. ET.

About EGFR Exon 20 Insertion-Mutant NSCLC

NSCLC is the most common form of lung cancer, accounting for approximately 85% of the estimated 1.8 million new cases of lung cancer diagnosed each year worldwide, according to the World Health Organization.^1,2 Patients with EGFR exon 20 insertion mutations make up only about 1-2% of patients with NSCLC.^3,4 This disease carries a worse prognosis than other EGFR mutations because there are currently no FDA-approved therapies that target exon 20 mutations, and current EGFR TKIs and chemotherapy provide limited benefit for these patients.

About Mobocertinib (TAK-788)

Mobocertinib is a potent, small-molecule TKI specifically designed to selectively target EGFR and HER2 exon 20 insertion mutations. In 2019, the U.S. FDA granted mobocertinib Orphan Drug Designation for the treatment of lung cancer with HER2 mutations or EGFR mutations including exon 20 insertion mutations.

Results from the ongoing Phase 1/2 trial of mobocertinib, which is evaluating the efficacy and safety of mobocertinib at 160 mg once daily in previously treated patients with EGFR exon 20 insertions, showed mobocertinib yielded a median progression-free survival (PFS) of 7.3 months and a confirmed overall response rate (ORR) of 43% (n=12/28) in patients with locally advanced or metastatic EGFR exon 20 insertion-mutant NSCLC. The safety profile of mobocertinib was manageable (N= 72). The most common treatment-related adverse events (AEs) were diarrhea (85%), nausea (43%), rash (36%), vomiting (29%) and decreased appetite (25%). These results were presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting.

The mobocertinib development program began in the NSCLC population and is expected to expand to additional underserved populations in other tumor types. Mobocertinib is an investigational drug for which efficacy and safety have not been established.

Takeda in Lung Cancer

Takeda is dedicated to expanding treatment options in the ALK+ NSCLC and EGFR/HER2 insertion-mutant NSCLC treatment landscapes. Our comprehensive programs include the following clinical trials to continue to address unmet needs for people living with lung cancer:

Mobocertinib:

• Phase 1/2 study evaluating the safety, pharmacokinetics and antitumor activity of oral EGFR/HER2 inhibitor mobocertinib in patients with NSCLC. This trial has completed enrollment.
• Phase 2 EXCLAIM, pivotal extension cohort of the Phase 1/2 trial, which was designed to evaluate the efficacy and safety of mobocertinib at 160 mg once daily in previously treated patients with EGFR exon 20 insertion mutations. This trial has completed enrollment.
• Phase 3 EXCLAIM-2, global, randomized study evaluating the efficacy of mobocertinib as a first-line treatment compared to platinum-based doublet chemotherapy in treatment-naïve patients with locally advanced or metastatic NSCLC whose tumors harbor EGFR exon 20 insertion mutations. This trial is now enrolling.
• Phase 1, open-label, multicenter, dose-escalation study evaluating the safety, tolerability and pharmacokinetics of mobocertinib in Japanese patients with locally advanced or metastatic NSCLC. This trial has completed enrollment.
• Phase 2 J-EXCLAIM, open-label, multicenter, study evaluating the efficacy of mobocertinib as a first-line treatment in Japanese patients with locally advanced or metastatic NSCLC whose tumors harbor EGFR exon 20 insertion mutations. This trial is now enrolling.
• Phase 1, open-label, multicenter, drug-drug interaction study of mobocertinib and midazolam, a sensitive CYP3A substrate, in patients with advanced NSCLC. This trial is now enrolling.

ALUNBRIG, a next-generation TKI designed to target and inhibit ALK molecular alterations:

• Phase 1/2 trial, which was designed to evaluate the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of ALUNBRIG. This trial has completed enrollment.
• Pivotal Phase 2 ALTA trial investigating the efficacy and safety of ALUNBRIG at two dosing regimens in patients with ALK+ locally advanced or metastatic NSCLC who had progressed on crizotinib. This trial has completed enrollment.
• Phase 3 ALTA-1L, global, randomized trial assessing the efficacy and safety of ALUNBRIG in comparison to crizotinib in patients with ALK+ locally advanced or metastatic NSCLC who have not received prior treatment with an ALK inhibitor. This trial has completed enrollment.
• Phase 2 J-ALTA, single-arm, multicenter trial in Japanese patients with ALK+ NSCLC, focusing on patients who have progressed on alectinib. This trial has completed enrollment.
• Phase 2 ALTA 2, global, single-arm trial evaluating ALUNBRIG in patients with advanced ALK+ NSCLC who have progressed on alectinib or ceritinib. This trial has completed enrollment.
• Phase 3 ALTA 3, global randomized trial comparing the efficacy and safety of ALUNBRIG versus alectinib in participants with ALK+ NSCLC who have progressed on crizotinib. This trial is now enrolling.

For additional information on the mobocertinib and ALUNBRIG clinical trials, please visit www.clinicaltrials.gov.

Takeda’s Commitment to Oncology

Our core R&D mission is to deliver novel medicines to patients with cancer worldwide through our commitment to science, breakthrough innovation and passion for improving the lives of patients. Whether it’s with our hematology therapies, our robust pipeline, or solid tumor medicines, we aim to stay both innovative and competitive to bring patients the treatments they need. For more information, visit www.takedaoncology.com.

About Takeda Pharmaceutical Company Limited

Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) is a global, values-based, R&D-driven biopharmaceutical leader headquartered in Japan, committed to bringing Better Health and a Brighter Future to patients by translating science into highly-innovative medicines. Takeda focuses its R&D efforts on four therapeutic areas: Oncology, Rare Diseases, Neuroscience, and Gastroenterology (GI). We also make targeted R&D investments in Plasma-Derived Therapies and Vaccines. We are focusing on developing highly innovative medicines that contribute to making a difference in people's lives by advancing the frontier of new treatment options and leveraging our enhanced collaborative R&D engine and capabilities to create a robust, modality-diverse pipeline. Our employees are committed to improving quality of life for patients and to working with our partners in health care in approximately 80 countries.

For more information, visit https://www.takeda.com.

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¹ World Health Organization. Latest Global Cancer Data. https://www.who.int/cancer/PRGlobocanFinal.pdf. Accessed May 11, 2019.

² American Cancer Society. What is Non-Small Cell Lung Cancer? https://www.cancer.org/cancer/non-small-cell-lung-cancer/about/what-is-non-small-cell-lung-cancer.html.

³ Riess, Jonathan W. Diverse EGFR Exon 20 Insertions and Co-Occurring Molecular Alterations Identified by Comprehensive Genomic Profiling of NSCLC. https://www.jto.org/article/S1556-0864(18)30770-6/fulltext. Accessed April 7, 2020.

⁴ Fang, Wenfeng. BMC Cancer. EGFR exon 20 insertion mutations and response to osimertinib in non-small-cell lung cancer. https://bmccancer.biomedcentral.com/articles/10.1186/s12885-019-5820-0. Accessed April 7, 2020.

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