Daiichi Sankyo Initiates Clinical Trial with its 4th DXd Antibody Drug Conjugate, DS-7300, in Collaboration with Sarah Cannon Research Institute

Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) and Sarah Cannon Research Institute (Sarah Cannon) announced today that the first patient has been dosed in a first-in-human phase 1/2 study evaluating DS-7300, an investigational B7-H3 targeting antibody drug conjugate (ADC), in patients with various advanced solid tumors that have progressed on standard treatments or for whom no standard treatment exists.

The study is the first in the strategic oncology partnership announced between Daiichi Sankyo and Sarah Cannon, designed to expedite and optimize global clinical development of Daiichi Sankyo's novel ADCs and other targeted cancer therapies by combining the operational and scientific expertise of both organizations.

DS-7300 is the fourth ADC in clinical development utilizing Daiichi Sankyo's proprietary DXd technology and was designed to target and deliver chemotherapy inside cancer cells that express the B7-H3 protein. B7-H3 is frequently overexpressed in various types of cancers and has been associated with disease progression and poor prognosis in many tumor types.¹ No B7-H3 targeting therapies are currently approved for treatment of any cancer.

"This first-in-human phase 1/2 trial will evaluate the potential for DS-7300 to serve as a new mode of targeted therapy for patients with several types of advanced cancers where the B7-H3 protein is overexpressed," said Antoine Yver, MD, MSc, EVP & Global Head of Oncology Research and Development, Daiichi Sankyo. "Based on our preclinical assessments, the trial will focus initially on patients with non-small cell lung, head and neck, esophageal, and other cancers. We also will continue to conduct important biomarker and translational research to further assess the role this promising therapeutic target may play in treatment of various cancers."

"Given the prevalence of B7-H3 in certain tumors, we hope this unique approach will help us to more effectively target a number of cancer types," said Johanna Bendell, MD, Chief Development Officer, Sarah Cannon. "By combining Sarah Cannon's expertise in developing novel therapies and Daiichi Sankyo's capabilities in compound development, we have been able to expand our reach to patients across the U.S. and Japan who vitally need advanced treatment options."

B7-H3 (B7 homologue 3) is a transmembrane protein belonging to the B7 family. B7-H3 plays a role in tumor growth as well as in immune response.^1,2 B7-H3 is highly expressed on various types of tumors including lung, head and neck, esophageal, prostate, endometrial and breast cancers.¹ In preclinical studies, DS-7300 demonstrated activity in B7-H3 expressing tumors, and activity was associated with target expression levels.

Based on initial preclinical research into the construct necessary for optimized safety and efficacy in B7-H3 expressing tumors, DS-7300 was engineered with a new proprietary Daiichi Sankyo technology, DAR-controlled conjugation, to create a drug-to-antibody ratio (DAR) of four. The technology has been used also to prepare DS-1062, Daiichi Sankyo's TROP2 ADC under clinical development in patients with NSCLC who have failed standard of care, including immune checkpoint inhibitors.

About the Study

The first-in-human, open-label phase 1/2 study will investigate the safety, tolerability and preliminary activity of DS-7300 in adult patients with advanced/unresectable or metastatic solid tumors that are refractory or intolerable to standard treatment or for whom no standard treatment exists.

The first part of the study (dose escalation) will assess the safety and tolerability of increasing doses of DS-7300 to determine the maximum tolerated dose (MTD) and recommended dose for expansion (RDE). This portion of the trial will enroll approximately 40 patients with advanced/unresectable or metastatic squamous cell head and neck cancers, squamous cell esophageal cancer, squamous and adenocarcinoma cell non-small cell lung cancer (NSCLC), and other tumor types (ten total). The second part of the study (dose expansion) will evaluate the safety, tolerability and preliminary activity of DS-7300 at the RDE and assess overall survival. This portion of the trial will include three cohorts of 40 patients each, potentially including patients with advanced/unresectable or metastatic squamous cell head and neck cancers, squamous cell esophageal cancer, and squamous NSCLC. Additional or alternative indications may be added to expansion cohorts based on preliminary signals of activity.

The study will evaluate safety endpoints including adverse events and efficacy endpoints including objective-response rate, duration of response, disease control rate, time to response, progression-free survival, and overall survival. Pharmacokinetic endpoints and exploratory biomarker and immunogenicity endpoints will also be assessed.

A total of approximately 160 patients are expected to be enrolled in this study in the U.S. and Japan. For more information, please visit ClinicalTrials.gov

About DS-7300

DS-7300 is an investigational B7-H3 targeting ADC and one of four ADCs under clinical development in Daiichi Sankyo's Cancer Enterprise pipeline. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ("payload") to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Designed using Daiichi Sankyo's proprietary DXd ADC technology, DS-7300 is comprised of a humanized anti-B7-H3 monoclonal antibody, which is attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based linker. It is designed to target and deliver chemotherapy inside cancer cells and reduce systemic exposure to the cytotoxic payload (or chemotherapy) compared to the way chemotherapy is commonly delivered.

DS-7300 is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.

About Daiichi Sankyo Cancer Enterprise

The mission of Daiichi Sankyo Cancer Enterprise is to leverage our world-class, innovative science and push beyond traditional thinking to create meaningful treatments for patients with cancer. We are dedicated to transforming science into value for patients, and this sense of obligation informs everything we do. Anchored by three pillars including our investigational Antibody Drug Conjugate Franchise, Acute Myeloid Leukemia Franchise and Breakthrough Science, we aim to deliver seven distinct new molecular entities over eight years during 2018 to 2025. Our powerful research engines include two laboratories for biologic/immuno-oncology and small molecules in Japan, and Plexxikon Inc., our small molecule structure-guided R&D center in Berkeley, CA. For more information, please visit: www.DSCancerEnterprise.com.

About Daiichi Sankyo

Daiichi Sankyo Group is dedicated to the creation and supply of innovative pharmaceutical therapies to improve standards of care and address diversified, unmet medical needs of people globally by leveraging our world-class science and technology. With more than 100 years of scientific expertise and a presence in more than 20 countries, Daiichi Sankyo and its 15,000 employees around the world draw upon a rich legacy of innovation and a robust pipeline of promising new medicines to help people. In addition to a strong portfolio of medicines for cardiovascular diseases, under the Group's 2025 Vision to become a "Global Pharma Innovator with Competitive Advantage in Oncology," Daiichi Sankyo is primarily focused on providing novel therapies in oncology, as well as other research areas centered around rare diseases and immune disorders. For more information, please visit: www.daiichisankyo.com.

About Sarah Cannon Research Institute

Sarah Cannon Research Institute is one of the world's leading clinical research organizations conducting community-based clinical trials throughout the United States and United Kingdom. Sarah Cannon's network of strategic sites includes hundreds of physicians who engage in research. With a focus on advancing therapies for patients, the organization has led more than 400 first-in-man clinical trials since its inception in 1993, and has been a clinical trial leader in the majority of approved cancer therapies over the last 10 years.

Additionally, Sarah Cannon offers management, regulatory, and other research support services for drug development and industry sponsors through its oncology-focused contract research organization (CRO), Sarah Cannon Development Innovations. As the CRO of Sarah Cannon, it leverages expert physician leadership to design and implement clinical trials that effectively and efficiently lead to rapid clinical development decisions. For more information, please visit sarahcannon.com.

¹ Zhang et al. Oncotarget. 2017 Nov 3; 8(54): 93156?93167.
² Castellanos J et al. Am J Clin Exp Immunol 2017;6(4):66-75.