Foundation Medicine and Takeda Announce Collaboration To Develop FoundationOne®CDx and FoundationOne®Liquid CDx as Companion Diagnostics for Takeda’s Late-Stage Lung Cancer Portfolio

Companion diagnostics will be developed to identify patients with NSCLC that harbor ALK fusions and EGFR Exon20 insertion mutations to match patients with appropriate targeted therapies from Takeda

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Foundation Medicine, Inc. and Takeda Pharmaceuticals USA, Inc., a wholly-owned subsidiary of Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK), today announced a collaboration for the development of Foundation Medicine’s tissue- and blood-based companion diagnostics for use with marketed and investigational treatments in Takeda’s late-stage lung cancer portfolio. If approved, the appropriate companion diagnostics would be used to identify patients who may be eligible for mobocertinib, an investigational drug being evaluated for the treatment of patients with epidermal growth factor receptor (EGFR) Exon20 insertion+ metastatic non-small cell lung cancer (mNSCLC), and ALUNBRIG® (brigatinib), Takeda’s tyrosine kinase inhibitor (TKI) recently FDA-approved to treat patients with TKI-naïve anaplastic lymphoma kinase-positive (ALK+) mNSCLC.

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NSCLC is the most common form of lung cancer, accounting for approximately 85 percent of the estimated 1.8 million new patients diagnosed each year worldwide;^{1 ,2} and forty percent of patients with NSCLC are diagnosed with metastatic disease.³ EGFR Exon20 insertion mutations occur in approximately 1-2 percent of patients with mNSCLC and these patients have no FDA-approved treatment options designed to target these Exon20 alterations.^{4, 5} ALK+ mNSCLC is a complex and aggressive form of lung cancer found in approximately 3-5 percent of patients with mNSCLC.^6,7,8

“Our collaboration with Foundation Medicine will address an urgent need for broad access to genomic tests, ultimately expanding treatment options and potentially improving outcomes for people with ALK+ and EGFR Exon20 insertion+ mNSCLC,” said Christopher Arendt, Head, Oncology Therapeutic Area Unit, Takeda. “Robust, accurate and timely testing is crucial to enable oncologists to make informed treatment decisions so that advanced cancer patients receive the optimal therapy for their disease.”

Foundation Medicine’s proven portfolio of FDA-approved comprehensive genomic profiling tests offer physicians both blood- and tissue-based testing options for detecting genomic alterations that help guide personalized treatment decisions. As companion diagnostics, FoundationOne®CDx and FoundationOne®Liquid CDx allow oncologists to identify patients who may be appropriate for FDA-approved targeted therapies. Through this collaboration, FoundationOne CDx and FoundationOne Liquid CDx will be developed for use with Takeda’s therapies.

“We’re proud to partner with Takeda on this important journey to allow more lung cancer patients to have access to genomic testing to inform personalized treatment decisions,” said Cindy Perettie, Chief Executive Officer at Foundation Medicine. “Takeda shares our patient-centric approach to research and development and mission to advance personalized cancer care. This collaboration leveraging our portfolio of FDA-approved genomic tests will accelerate our shared vision and make precision medicine a reality for more patients.”

About FoundationOne Liquid CDx

FoundationOne Liquid CDx is a qualitative next generation sequencing based in vitro diagnostic test for prescription use only that uses targeted high throughput hybridization-based capture technology to analyze 324 genes utilizing circulating cell-free DNA (cfDNA) isolated from plasma derived from anti-coagulated peripheral whole blood of advanced cancer patients. The test is FDA-approved to report short variants in 311 genes, including rearrangements and copy number losses in BRCA1 and BRCA2, and is a companion diagnostic to identify patients who may benefit from treatment with specific targeted therapies (listed in Table 1 of the Intended Use) in accordance with the approved therapeutic product labeling. Additional genomic findings may be reported and are not prescriptive or conclusive for labeled use of any specific therapeutic product. Use of the test does not guarantee a patient will be matched to a treatment. A negative result does not rule out the presence of an alteration. Patients who are negative for companion diagnostic mutations should be reflexed to tumor tissue testing and mutation status confirmed using an FDA-approved tumor tissue test, if available. For the complete label, including companion diagnostic indications and complete risk information, please visit www.F1LCDxLabel.com.

About FoundationOne CDx

FoundationOne CDx is a next-generation sequencing based in vitro diagnostic device for detection of substitutions, insertion and deletion alterations (indels), and copy number alterations (CNAs) in 324 genes and select gene rearrangements, as well as genomic signatures including microsatellite instability (MSI) and tumor mutational burden (TMB) using DNA isolated from formalin-fixed paraffin embedded (FFPE) tumor tissue specimens. FoundationOne CDx is for prescription use only and is intended as a companion diagnostic to identify patients who may benefit from treatment with certain targeted therapies in accordance with their approved therapeutic product labeling. Additionally, FoundationOne CDx is intended to provide tumor mutation profiling to be used by qualified health care professionals in accordance with professional guidelines in oncology for patients with solid malignant neoplasms. Use of the test does not guarantee a patient will be matched to a treatment. A negative result does not rule out the presence of an alteration. Some patients may require a biopsy. For a full list of targeted therapies for which FoundationOne CDx is indicated as a companion diagnostic, please visit http://www.F1CDxLabel.com.

About Mobocertinib (TAK-788)

Mobocertinib is a potent, small-molecule TKI specifically designed to selectively target epidermal growth factor receptor (EGFR) and human EGFR2 (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 Exon20 insertion+ metastatic non-small cell lung cancer (mNSCLC). In April 2020, mobocertinib received Breakthrough Therapy Designation from the FDA for patients with EGFR Exon20 insertion+ mNSCLC whose disease has progressed on or after platinum-based chemotherapy. 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.

About ALUNBRIG® (brigatinib)

ALUNBRIG is a potent and selective next-generation tyrosine kinase inhibitor (TKI) that was designed to target anaplastic lymphoma kinase (ALK) molecular alterations.

ALUNBRIG is approved in the U.S. and European Union (EU) as a first-line treatment for patients with ALK-positive (ALK+) metastatic non-small cell lung cancer (mNSCLC) previously not treated with an ALK inhibitor. ALUNBRIG is also approved in more than 40 countries, including the U.S., Canada and the EU, for the treatment of people living with ALK+ mNSCLC who have taken the medicine crizotinib, but their NSCLC has worsened or they cannot tolerate taking crizotinib.

About Foundation Medicine

Foundation Medicine is a molecular information company dedicated to a transformation in cancer care in which treatment is informed by a deep understanding of the genomic changes that contribute to each patient's unique cancer. The company offers a full suite of comprehensive genomic profiling assays to identify the molecular alterations in a patient’s cancer and match them with relevant targeted therapies, immunotherapies and clinical trials. Foundation Medicine’s molecular information platform aims to improve day-to-day care for patients by serving the needs of clinicians, academic researchers and drug developers to help advance the science of molecular medicine in cancer. For more information, please visit www.FoundationMedicine.com or follow Foundation Medicine on Twitter (@FoundationATCG).

Foundation Medicine^® and FoundationOne^® are registered trademarks of Foundation Medicine, Inc.

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.

ALUNBRIG IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Interstitial Lung Disease (ILD)/Pneumonitis: Severe, life-threatening, and fatal pulmonary adverse reactions consistent with interstitial lung disease (ILD)/pneumonitis have occurred with ALUNBRIG. In the ALUNBRIG arm of trial ALTA 1L (180 mg once daily), ILD/pneumonitis occurred in 5.1% of patients receiving ALUNBRIG. ILD/pneumonitis occurred within 8 days of initiation of ALUNBRIG in 2.9% of patients, with Grade 3 to 4 reactions occurring in 2.2% of patients. In Trial ALTA, ILD/pneumonitis occurred in 3.7% of patients in the 90 mg group (90 mg once daily) and 9.1% of patients in the 90→180 mg group (180 mg once daily with 7-day lead-in at 90 mg once daily). Adverse reactions consistent with possible ILD/pneumonitis occurred early within 9 days of initiation of ALUNBRIG (median onset was 2 days) in 6.4% of patients, with Grade 3 to 4 reactions occurring in 2.7%. Monitor for new or worsening respiratory symptoms (e.g., dyspnea, cough, etc.), particularly during the first week of initiating ALUNBRIG. Withhold ALUNBRIG in any patient with new or worsening respiratory symptoms, and promptly evaluate for ILD/pneumonitis or other causes of respiratory symptoms (e.g., pulmonary embolism, tumor progression, and infectious pneumonia). For Grade 1 or 2 ILD/pneumonitis, either resume ALUNBRIG with dose reduction after recovery to baseline or permanently discontinue ALUNBRIG. Permanently discontinue ALUNBRIG for Grade 3 or 4 ILD/pneumonitis or recurrence of Grade 1 or 2 ILD/pneumonitis.

Hypertension: In the ALUNBRIG arm of trial ALTA 1L (180 mg once daily), hypertension was reported in 32% of patients receiving ALUNBRIG; Grade 3 hypertension occurred in 13% of patients. In ALTA, hypertension was reported in 11% of patients in the 90 mg group who received ALUNBRIG and 21% of patients in the 90→180 mg group. Grade 3 hypertension occurred in 5.9% of patients overall. Control blood pressure prior to treatment with ALUNBRIG. Monitor blood pressure after 2 weeks and at least monthly thereafter during treatment with ALUNBRIG. Withhold ALUNBRIG for Grade 3 hypertension despite optimal antihypertensive therapy. Upon resolution or improvement to Grade 1, resume ALUNBRIG at the same dose. Consider permanent discontinuation of treatment with ALUNBRIG for Grade 4 hypertension or recurrence of Grade 3 hypertension. Use caution when administering ALUNBRIG in combination with antihypertensive agents that cause bradycardia.

Bradycardia: In the ALUNBRIG arm of trial ALTA 1L (180 mg once daily), heart rates less than 50 beats per minute (bpm) occurred in 8.1% of patients receiving ALUNBRIG. Grade 3 bradycardia occurred in 1 patient (0.7%). In ALTA, heart rates less than 50 beats per minute (bpm) occurred in 5.7% of patients in the 90 mg group and 7.6% of patients in the 90→180 mg group. Grade 2 bradycardia occurred in 1 (0.9%) patient in the 90 mg group. Monitor heart rate and blood pressure during treatment with ALUNBRIG. Monitor patients more frequently if concomitant use of drug known to cause bradycardia cannot be avoided. For symptomatic bradycardia, withhold ALUNBRIG and review concomitant medications for those known to cause bradycardia. If a concomitant medication known to cause bradycardia is identified and discontinued or dose adjusted, resume ALUNBRIG at the same dose following resolution of symptomatic bradycardia; otherwise, reduce the dose of ALUNBRIG following resolution of symptomatic bradycardia. Discontinue ALUNBRIG for life-threatening bradycardia if no contributing concomitant medication is identified.

Visual Disturbance: In the ALUNBRIG arm of trial ALTA 1L (180 mg once daily), Grade 1 or 2 adverse reactions leading to visual disturbance including blurred vision, photophobia, photopsia, and reduced visual acuity were reported in 7.4% of patients receiving ALUNBRIG. In ALTA, adverse reactions leading to visual disturbance including blurred vision, diplopia, and reduced visual acuity, were reported in 7.3% of patients treated with ALUNBRIG in the 90 mg group and 10% of patients in the 90→180 mg group. Grade 3 macular edema and cataract occurred in one patient each in the 90→180 mg group. Advise patients to report any visual symptoms. Withhold ALUNBRIG and obtain an ophthalmologic evaluation in patients with new or worsening visual symptoms of Grade 2 or greater severity. Upon recovery of Grade 2 or Grade 3 visual disturbances to Grade 1 severity or baseline, resume ALUNBRIG at a reduced dose. Permanently discontinue treatment with ALUNBRIG for Grade 4 visual disturbances.

Creatine Phosphokinase (CPK) Elevation: In the ALUNBRIG arm of trial ALTA 1L (180 mg once daily), creatine phosphokinase (CPK) elevation occurred in 81% of patients who received ALUNBRIG. The incidence of Grade 3 or 4 CPK elevation was 24%. Dose reduction for CPK elevation occurred in 15% of patients. In ALTA, CPK elevation occurred in 27% of patients receiving ALUNBRIG in the 90 mg group and 48% of patients in the 90 mg→180 mg group. The incidence of Grade 3‑4 CPK elevation was 2.8% in the 90 mg group and 12% in the 90→180 mg group. Dose reduction for CPK elevation occurred in 1.8% of patients in the 90 mg group and 4.5% in the 90→180 mg group. Advise patients to report any unexplained muscle pain, tenderness, or weakness. Monitor CPK levels during ALUNBRIG treatment. Withhold ALUNBRIG for Grade 3 or 4 CPK elevation with Grade 2 or higher muscle pain or weakness. Upon resolution or recovery to Grade 1 CPK elevation or baseline, resume ALUNBRIG at the same dose or at a reduced dose.

Pancreatic Enzyme Elevation: In the ALUNBRIG arm of trial ALTA 1L (180 mg once daily), amylase elevation occurred in 52% of patients and Grade 3 or 4 amylase elevation occurred in 6.8% of patients. Lipase elevations occurred in 59% of patients and Grade 3 or 4 lipase elevation occurred in 17% of patients. In ALTA, amylase elevation occurred in 27% of patients in the 90 mg group and 39% of patients in the 90→180 mg group. Lipase elevations occurred in 21% of patients in the 90 mg group and 45% of patients in the 90→180 mg group. Grade 3 or 4 amylase elevation occurred in 3.7% of patients in the 90 mg group and 2.7% of patients in the 90→180 mg group. Grade 3 or 4 lipase elevation occurred in 4.6% of patients in the 90 mg group and 5.5% of patients in the 90→180 mg group. Monitor lipase and amylase during treatment with ALUNBRIG. Withhold ALUNBRIG for Grade 3 or 4 pancreatic enzyme elevation. Upon resolution or recovery to Grade 1 or baseline, resume ALUNBRIG at the same dose or at a reduced dose.

Hyperglycemia: In the ALUNBRIG arm of trial ALTA 1L (180 mg once daily), 56% of patients who received ALUNBRIG experienced new or worsening hyperglycemia. Grade 3 hyperglycemia, based on laboratory assessment of serum fasting glucose levels, occurred in 7.5% of patients. In ALTA, 43% of patients who received ALUNBRIG experienced new or worsening hyperglycemia. Grade 3 hyperglycemia, based on laboratory assessment of serum fasting glucose levels, occurred in 3.7% of patients. Two of 20 (10%) patients with diabetes or glucose intolerance at baseline required initiation of insulin while receiving ALUNBRIG. Assess fasting serum glucose prior to initiation of ALUNBRIG and monitor periodically thereafter. Initiate or optimize anti-hyperglycemic medications as needed. If adequate hyperglycemic control cannot be achieved with optimal medical management, withhold ALUNBRIG until adequate hyperglycemic control is achieved and consider reducing the dose of ALUNBRIG or permanently discontinuing ALUNBRIG.

Embryo-Fetal Toxicity: Based on its mechanism of action and findings in animals, ALUNBRIG can cause fetal harm when administered to pregnant women. There are no clinical data on the use of ALUNBRIG in pregnant women. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with ALUNBRIG and for at least 4 months following the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment and for at least 3 months after the last dose of ALUNBRIG.

ADVERSE REACTIONS

In ALTA 1L, serious adverse reactions occurred in 33% of patients receiving ALUNBRIG. The most common serious adverse reactions other than disease progression were pneumonia (4.4%), ILD/pneumonitis (3.7%), pyrexia (2.9%), dyspnea (2.2%), pulmonary embolism (2.2%), and asthenia (2.2%). Fatal adverse reactions other than disease progression occurred in 2.9% of patients and included pneumonia (1.5%), cerebrovascular accident (0.7%), and multiple organ dysfunction syndrome (0.7%).

In ALTA, serious adverse reactions occurred in 38% of patients in the 90 mg group and 40% of patients in the 90→180 mg group. The most common serious adverse reactions were pneumonia (5.5% overall, 3.7% in the 90 mg group, and 7.3% in the 90→180 mg group) and ILD/pneumonitis (4.6% overall, 1.8% in the 90 mg group and 7.3% in the 90→180 mg group). Fatal adverse reactions occurred in 3.7% of patients and consisted of pneumonia (2 patients), sudden death, dyspnea, respiratory failure, pulmonary embolism, bacterial meningitis and urosepsis (1 patient each).

The most common adverse reactions (≥25%) with ALUNBRIG were diarrhea (49%), fatigue (39%), nausea (39%), rash (38%), cough (37%), myalgia (34%), headache (31%), hypertension (31%), vomiting (27%), and dyspnea (26%).

DRUG INTERACTIONS

CYP3A Inhibitors: Avoid coadministration of ALUNBRIG with strong or moderate CYP3A inhibitors. Avoid grapefruit or grapefruit juice as it may also increase plasma concentrations of brigatinib. If coadministration of a strong or moderate CYP3A inhibitor cannot be avoided, reduce the dose of ALUNBRIG.

CYP3A Inducers: Avoid coadministration of ALUNBRIG with strong or moderate CYP3A inducers. If coadministration of moderate CYP3A inducers cannot be avoided, increase the dose of ALUNBRIG.

CYP3A Substrates:Coadministration of ALUNBRIG with sensitive CYP3A substrates, including hormonal contraceptives, can result in decreased concentrations and loss of efficacy of sensitive CYP3A substrates.

USE IN SPECIFIC POPULATIONS

Pregnancy: ALUNBRIG can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus.

Lactation: There are no data regarding the secretion of brigatinib in human milk or its effects on the breastfed infant or milk production. Because of the potential adverse reactions in breastfed infants, advise lactating women not to breastfeed during treatment with ALUNBRIG.

Females and Males of Reproductive Potential:

Pregnancy Testing: Verify pregnancy status in females of reproductive potential prior to initiating ALUNBRIG.

Contraception: Advise females of reproductive potential to use effective non-hormonal contraception during treatment with ALUNBRIG and for at least 4 months after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with ALUNBRIG and for at least 3 months after the final dose.

Infertility:ALUNBRIG may cause reduced fertility in males.

Pediatric Use: The safety and effectiveness of ALUNBRIG in pediatric patients have not been established.

Geriatric Use: Of the 359 patients enrolled in the ALTA 1L ALUNBRIG arm and in ALTA, 26.7% were 65 and older and 7.5% were 75 and older. No clinically relevant differences in safety or efficacy were observed between patients ≥65 years and younger patients.

Hepatic or Renal Impairment: No dose adjustment is recommended for patients with mild or moderate hepatic impairment or mild or moderate renal impairment. Reduce the dose of ALUNBRIG for patients with severe hepatic impairment or severe renal impairment.

Please see the full U.S. Prescribing Information for ALUNBRIG at www.ALUNBRIG.com.

Forward-Looking Statements

This press release and any materials distributed in connection with this press release may contain forward-looking statements, beliefs or opinions regarding Takeda’s future business, future position and results of operations, including estimates, forecasts, targets and plans for Takeda. Without limitation, forward-looking statements often include words such as “targets”, “plans”, “believes”, “hopes”, “continues”, “expects”, “aims”, “intends”, “ensures”, “will”, “may”, “should”, “would”, “could” “anticipates”, “estimates”, “projects” or similar expressions or the negative thereof. These forward-looking statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those expressed or implied by the forward-looking statements: the economic circumstances surrounding Takeda’s global business, including general economic conditions in Japan and the United States; competitive pressures and developments; changes to applicable laws and regulations; the success of or failure of product development programs; decisions of regulatory authorities and the timing thereof; fluctuations in interest and currency exchange rates; claims or concerns regarding the safety or efficacy of marketed products or product candidates; the impact of health crises, like the novel coronavirus pandemic, on Takeda and its customers and suppliers, including foreign governments in countries in which Takeda operates, or on other facets of its business; the timing and impact of post-merger integration efforts with acquired companies; the ability to divest assets that are not core to Takeda’s operations and the timing of any such divestment(s); and other factors identified in Takeda’s most recent Annual Report on Form 20-F and Takeda’s other reports filed with the U.S. Securities and Exchange Commission, available on Takeda’s website at: https://www.takeda.com/investors/reports/sec-filings/ or at www.sec.gov. Takeda does not undertake to update any of the forward-looking statements contained in this press release or any other forward-looking statements it may make, except as required by law or stock exchange rule. Past performance is not an indicator of future results and the results or statements of Takeda in this press release may not be indicative of, and are not an estimate, forecast, guarantee or projection of Takeda’s future results.

Source: Foundation Medicine

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. Accessed May 11, 2019.

³ Cancer Treatment Centers of America. Lung Cancer Stages https://www.cancercenter.com/cancer-types/lung-cancer/stages#:~:text=What%20is%20stage%20IV%20(stage,they%20are%20in%20stage%20IV.

⁴ 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

⁵ 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.

⁶ Gainor JF, Varghese AM, Ou SH, et al. Clin Cancer Res. 2013;19(15):4273-81.

⁷ Koivunen JP, Mermel C, Zejnullahu K, et al. Clin Cancer Res. 2008; 14(13):4275-83.

⁸ Wong DW, Leung EL, So KK, et al. Cancer. 2009; 115(8):1723-33.

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Foundation Medicine:
Erin Smith, 262-914-2779
pr@foundationmedicine.com

Takeda:
Lauren Padovan, 1-617-444-1419
lauren.padovan@takeda.com

Source: Foundation Medicine