Initial Results from MOUNTAINEER Trial Show Antitumor Activity of Tucatinib Combination in HER2-Positive Metastatic Colorectal Cancer

– First Presentation of Tucatinib With Trastuzumab in Metastatic Colorectal Cancer –

– Findings Presented Today at the European Society for Medical Oncology (ESMO) 2019 Congress –

BARCELONA, Spain–(BUSINESS WIRE)–Seattle Genetics, Inc. (Nasdaq:SGEN) today announced that initial data were presented from the single arm phase 2 clinical trial known as MOUNTAINEER. The trial is evaluating the investigational agent tucatinib in combination with trastuzumab (Herceptin^®) in patients with HER2-positive (HER2+), RAS wild-type metastatic colorectal cancer (mCRC) after treatment with first- and second-line standard-of-care therapies. The regimen demonstrated encouraging antitumor activity and was well tolerated.

Tucatinib is an oral, small molecule tyrosine kinase inhibitor that is highly selective for HER2. HER2 amplification or overexpression occurs in approximately three-to-five percent of all patients with mCRC.^1,2 The results were presented during a poster discussion session today at the European Society for Medical Oncology (ESMO) 2019 Congress in Barcelona, Spain (Abstract #527PD).

Initial results from 23 patients evaluable for clinical/radiographic response are below.

• Objective response rate (ORR) was 52.2 percent (95% Confidence Interval [CI], 30.6-73.2) with a median duration of response of 10.4 months (95% CI, 6.0-NE)
• Median progression-free survival (PFS) was 8.1 months (95% CI, 3.8-NE)
• Median overall survival (OS) was 18.7 months (95% CI, 12.3-NE)
• The combination of tucatinib and trastuzumab was well tolerated. The most common treatment-related adverse events were Grade 1 in severity and included increased aspartate aminotransferase (AST, 38.5 percent; all Grade 1) increased alanine aminotransferase (ALT, 23.1 percent; all Grade 1), and diarrhea (23.1 percent; one Grade 1, four Grade 2, one Grade 3). There were no Grade 4 or 5 treatment-related adverse events.

“It’s exciting to see the initial results from the MOUNTAINEER trial. Tucatinib is a potent and selective inhibitor of HER2, and the combination of tucatinib and trastuzumab demonstrated significant activity for heavily pre-treated patients with HER2-positive metastatic colorectal cancer,” said John H. Strickler, M.D., Duke University Medical Center.

“There is an unmet clinical need for new treatments for patients with HER2-positive metastatic colorectal cancer,” said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. “The trial demonstrated that tucatinib has the potential to play a role in the treatment of colorectal cancer. We look forward to developing tucatinib in combination with trastuzumab and other therapies for the treatment of HER2-positive metastatic colorectal cancer.”

About MOUNTAINEER

MOUNTAINEER is a multi-center, open label, single-arm phase 2 clinical trial of tucatinib in combination with trastuzumab in patients with HER2-positive, RAS wildtype metastatic or unresectable colorectal cancer. The primary endpoint of the trial is objective response rate by RECIST (Response Evaluation Criteria in Solid Tumors) v1.1 criteria. Progression-free survival, duration of response, overall survival and safety and tolerability of the combination regimen are secondary objectives. Results for 26 patients were evaluated in this analysis, and enrollment is ongoing. Three of the 26 patients who are on active treatment were recently enrolled at the time of this analysis and had not yet received first radiographic assessment of response.

MOUNTAINEER is a Seattle Genetics-sponsored multi-site clinical trial initiated by the Academic and Community Cancer Research United (ACCRU) Network. ACCRU is a non-profit cancer research network comprised of more than 100 academic and community cancer centers across the United States. Seattle Genetics is now responsible for this ongoing clinical trial.

About Tucatinib

Tucatinib is an investigational, orally bioavailable, potent tyrosine kinase inhibitor that is highly selective for HER2 without significant inhibition of EGFR. Inhibition of EGFR has been associated with significant toxicities, including skin rash and diarrhea. Tucatinib has shown activity as a single agent and in combination with both chemotherapy and other HER2 directed agents such as trastuzumab.^3,4 Studies of tucatinib in these combinations have shown activity both systemically and in brain metastases. HER2 is a growth factor receptor that is overexpressed in multiple cancers, including breast, ovarian, colorectal and gastric cancers. HER2 mediates cell growth, differentiation and survival. Tumors that overexpress HER2 are more aggressive and historically have been associated with poor overall survival compared with HER2-negative cancers. Tucatinib has been granted orphan drug designation by the FDA for the treatment of HER2-positive metastatic colorectal cancer and breast cancer patients with brain metastases.

About Colorectal Cancer

Colorectal cancer is the second leading cause of cancer death in the United States (U.S.).⁵ In 2019, it is estimated there will be 145,600 new cases and 51,020 deaths in the U.S.⁵ Approximately 21 percent of U.S. patients with colorectal cancer are diagnosed at the advanced stage. ⁵ According to the U.S. Centers for Disease Control and Prevention, the most effective way to reduce the risk of colorectal cancer is routine screening beginning at age 50. In colorectal cancer, human epidermal growth factor receptor 2 (HER2) is overexpressed in three-to-five percent of patients.^1,2 There are currently no therapies approved that specifically target HER2 in colorectal cancer.

About Seattle Genetics

Seattle Genetics, Inc. is an emerging multi-product, global biotechnology company that develops and commercializes transformative therapies targeting cancer to make a meaningful difference in people’s lives. ADCETRIS^® (brentuximab vedotin) utilizes the company’s industry-leading antibody-drug conjugate (ADC) technology and is currently approved for the treatment of multiple CD30-expressing lymphomas. Beyond ADCETRIS, the company has established a pipeline of novel targeted therapies at various stages of clinical testing, including three in ongoing pivotal trials for solid tumors. Enfortumab vedotin for metastatic urothelial cancer and tisotumab vedotin for metastatic cervical cancer utilize our proprietary ADC technology. Tucatinib, a small molecule tyrosine kinase inhibitor, is in a pivotal trial for HER2-positive metastatic breast cancer. In addition, we are leveraging our expertise in empowered antibodies to build a portfolio of proprietary immuno-oncology agents in clinical trials targeting hematologic malignancies and solid tumors. The company is headquartered in Bothell, Washington, and has a European office in Switzerland. For more information on our robust pipeline, visit www.seattlegenetics.com and follow @SeattleGenetics on Twitter.

Forward Looking Statements

Certain of the statements made in this press release are forward looking, such as those, among others, relating to the possible efficacy, safety and the therapeutic uses of tucatinib, and anticipated clinical development activities including ongoing and future clinical trials and potential regulatory actions. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the difficulty and uncertainty of pharmaceutical product development, including the risks that Seattle Genetics may experience delays, setbacks or failures in its clinical development programs due to potential lack of efficacy, adverse events or adverse regulatory actions as tucatinib advances in clinical trials even after promising results in earlier clinical trials. More information about the risks and uncertainties faced by Seattle Genetics is contained under the caption “Risk Factors” included in the company’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2019 filed with the Securities and Exchange Commission. Seattle Genetics disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

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Contacts

Media:

Monique Greer

(425) 527-4641

[email protected]

Investors:

Peggy Pinkston

(425) 527-4160

[email protected]