UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 20-F (Mark One) ☐ REGISTRATION STATEMENT PURSUANT TO SECTION 12(b) OR (g) OF THE SECURITIES EXCHANGE ACT OF 1934 OR ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2022 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 OR ☐ SHELL COMPANY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 19 ...

Clinical Trial Results - ZYNLONTA achieved a 48.3% overall response rate (ORR) and a 24.8% complete response rate (CRR) in a pivotal Phase 2 clinical trial for relapsed or refractory DLBCL [305]. - Cami demonstrated a 66.3% ORR and a 27.7% CRR in a pivotal Phase 2 clinical trial for relapsed or refractory Hodgkin lymphoma [308]. - The overall response rate (ORR) for ZYNLONTA was 48.3%, with 36 patients (24.8%) achieving a complete response (CR) and 34 patients (23.4%) achieving a partial response (PR) [419]. - In a Phase 1 clinical trial, 23.4% of patients with relapsed or refractory DLBCL achieved a complete response, resulting in an overall response rate (ORR) of 42.3% [408]. - For patients with relapsed or refractory MCL, 33.3% achieved a complete response, resulting in a 46.7% ORR [410]. - In the Phase 1 trial for relapsed or refractory T-cell lymphoma, the ORR was 44.0%, with 8.0% achieving CR [453]. - In the pivotal Phase 2 clinical trial for Cami, a 66.3% ORR and a 27.7% CRR were observed in heavily pre-treated patients with relapsed or refractory Hodgkin lymphoma [433]. - The most common grade ≥3 treatment-emergent adverse events (TEAEs) for Cami included hypophosphatemia (7.7%), maculopapular rash (6.8%), and thrombocytopenia (6.8%) [430]. Patient Population and Unmet Medical Need - The current addressable patient population for ZYNLONTA in the United States is approximately 6,000 patients [305]. - Approximately 40% of DLBCL patients require second-line therapy after first-line treatment, highlighting the need for effective alternatives like ZYNLONTA [364]. - For follicular lymphoma, approximately 55% of patients require second-line therapy, indicating a significant unmet medical need that ZYNLONTA could address [368]. - Mantle cell lymphoma has an estimated 6,000 new cases in the US and EU5 in 2020, with rapid fatality if left untreated, underscoring the urgency for effective treatments [372]. - Approximately 70% of patients with MCL require second-line therapy, and about 65% of those will need third-line therapy, indicating a significant unmet medical need for alternative treatments [373]. - T-cell lymphoma has an estimated 13,000 new cases in the United States and EU5 in 2020, highlighting the urgency for novel therapies due to limited treatment options [374]. - In Hodgkin lymphoma, approximately 15% of patients require second-line therapy, and about 50% of those will need third-line therapy [380]. - Approximately 40% of the estimated 60,600 DLBCL patients diagnosed annually in the United States and EU5 will relapse or have refractory disease, representing a high unmet medical need [388]. - The addressable incident patient population for ZYNLONTA in relapsed or refractory DLBCL is estimated at approximately 11,000 patients per year in the United States and EU5 [388]. Drug Development and Approvals - ZYNLONTA received accelerated approval from the FDA on April 23, 2021, for adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy [316]. - The Marketing Authorisation Application (MAA) for ZYNLONTA in the EU has been validated by the European Medicines Agency (EMA) [317]. - A confirmatory Phase 3 clinical trial of ZYNLONTA in combination with rituximab is currently enrolling patients [306]. - The company plans to initiate a frontline study of ZYNLONTA combined with rituximab in frail patients in the second half of 2022 [306]. - The company aims to maximize the commercial potential of ZYNLONTA through its own infrastructure and strategic collaborations, including a joint venture with Overland Pharmaceuticals in Greater China and Singapore [324]. - The commercialization strategy for ZYNLONTA includes a seasoned commercial organization and strategic collaborations in regions like greater China and Japan to maximize its potential [392]. - ZYNLONTA is being developed for use in combination with rituximab for both second-line and frontline treatment in unfit or frail DLBCL patients, expanding its market opportunity [390]. Pipeline and Research Initiatives - The company is advancing a broad pipeline with four clinical-stage product candidates and two preclinical product candidates [314]. - The company aims to broaden the use of its ADCs to a wide range of hematological and solid tumor indications [316]. - The company is continuously discovering and developing clinical and product candidates to expand its portfolio, addressing high unmet medical needs in cancer treatment [323]. - The company has evaluated over 170 targets and is currently pursuing 11 ADC targets and 10 XDC targets in clinical and preclinical programs [348]. - The company has submitted six INDs since 2015 and is working with collaborators on two additional INDs for its product candidates [352]. - The company is applying multi-omics approaches to identify genetic signatures that may predict response to ZYNLONTA [417]. Safety and Tolerability - The most common Grade ≥3 treatment-emergent adverse events (TEAEs) in DLBCL patients included neutrophil count decreased (38.1%) and platelet count decreased (26.6%) [407]. - The clinical trial for Cami has shown a manageable tolerability profile, which is crucial given the high unmet medical need in the patient population [433]. - 14.5% of patients reported Grade ≥3 treatment-emergent adverse events (TEAEs), with hypophosphatemia at 7.7% and maculopapular rash at 6.8% [459]. - 7.7% of patients discontinued treatment due to TEAEs, and one patient died due to disease progression [462]. Mechanism of Action and Technology - ADCs using next-generation PBD technology are being developed, which are approximately 100 times more potent than currently marketed ADC warheads [342]. - The PBD dimer warheads in ADCs have shown a manageable tolerability profile in preclinical studies and clinical trials to date [342]. - PBD-based ADCs create interstrand cross-links in DNA that persist in target cells, allowing targeting of slowly proliferating cancer cells, including cancer stem cells [345]. - The bystander effect of PBD warheads enables them to diffuse into neighboring cells, potentially increasing the effectiveness of ADCs in heterogeneous tumor environments [346]. - The company has developed PBD-based warheads that require fewer molecules for effective cell killing, potentially increasing the range of cancers treatable with ADCs [344].