ADC Therapeutics(ADCT) - 2022 Q4 - Annual Report

Product Approval and Market Potential - ADC Therapeutics reported that its flagship product, ZYNLONTA®, received accelerated FDA approval on April 23, 2021, for treating adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy[174]. - The European Commission granted conditional marketing authorization for ZYNLONTA on December 20, 2022, for treating relapsed or refractory DLBCL in third or later lines of therapy[179]. - Approximately 60% of CAR-T patients are expected to relapse, and 27% of surveyed physicians have not referred any patients for CAR-T therapy in the last three years, indicating a significant market opportunity for ZYNLONTA[176]. - In 2022, there were an estimated 154,500 new cases of non-Hodgkin lymphoma in the US and EU5, highlighting the market potential for the company's therapies[215]. Clinical Trials and Efficacy - The overall response rate (ORR) in the Phase 2 trial of ZYNLONTA combined with rituximab was reported at 75%, with a complete response (CR) rate of 40%[236]. - The confirmatory clinical trial LOTIS-5 is expected to enroll approximately 350 patients, focusing on progression-free survival (PFS) as the primary objective[243][244]. - ZYNLONTA demonstrated favorable clinical activity across various patient populations, including a 54.2% overall response rate in germinal center B-cell DLBCL patients[269]. - The median duration of response (DoR) for patients achieving a response was 13.37 months, with a median progression-free survival of 4.93 months and median overall survival of 9.53 months[275]. - In the Phase 1 clinical trial for relapsed or refractory DLBCL, 32 patients (23.4%) achieved a complete response and 26 patients (19.0%) achieved a partial response, resulting in an overall response rate (ORR) of 42.3%[254]. Safety and Adverse Events - Grade ≥3 treatment-emergent adverse events (TEAEs) were reported in 107 patients (73.8%), with the most common being neutropenia (26.2%) and thrombocytopenia (17.9%)[265]. - Treatment-related adverse events led to discontinuation in 27 patients (18.6%), with gamma-glutamyltransferase increase being the most common reason[266]. - The company’s ADCs have demonstrated a manageable tolerability profile in preclinical studies and clinical trials, indicating a favorable safety profile[196]. Pipeline and Development Strategy - ADC Therapeutics is advancing its clinical-stage pipeline with two company-sponsored candidates, ADCT-901 and ADCT-601, and one candidate, ADCT-602, developed in collaboration with a partner[180]. - The company is exploring ZYNLONTA's potential in earlier lines of therapy through various clinical trials, including LOTIS-5, LOTIS-9, and LOTIS-7, which involve combinations with rituximab and other anti-cancer agents[177][178]. - The company is committed to addressing high unmet medical needs through its PBD-based pipeline, which includes both clinical-stage and preclinical-stage candidates[180]. - The company aims to evaluate ZYNLONTA in combination with other therapies for various types of relapsed or refractory B-cell non-Hodgkin lymphomas[236]. Technology and Innovation - ADC Therapeutics leverages its validated technology platform in highly potent PBD-based ADCs to transform treatment paradigms for patients with hematologic malignancies and solid tumors[174]. - The company has developed next-generation PBD-based antibody drug conjugates (ADCs) that are approximately 100 times more potent than currently marketed ADC warheads[196]. - The company is exploring novel conjugation and linker technologies to enhance the therapeutic index of its product candidates, including GlycoConnect/Hydraspace technology[355]. Competitive Landscape - The biotechnology industry is characterized by fierce competition, with major competitors including AbbVie, Daiichi Sankyo, and Roche, among others[367]. - Current third-line treatment options for relapsed or refractory DLBCL include CAR-T and polatuzumab, with ZYNLONTA potentially competing in the second-line treatment space[368]. - The company faces competition based on safety, effectiveness, marketing approvals, and pricing strategies, which may impact market acceptance[369]. Intellectual Property - The company has over 400 patents issued in the U.S. and other countries, with expirations ranging from 2023 to 2043, and numerous pending patent applications[363]. - As of December 31, 2022, the company co-owns approximately 40 patent families directed to ADCs with PBD warheads, with expected patent expirations between 2033 and 2042[364]. - The company has six patent families directed to the ZYNLONTA ADC product, with expected patent expirations between 2033 and 2042[365].