EX-99.2 3 dp204839_ex9902.htm EXHIBIT 99.2

 

Exhibit 99.2

 

Business Update January 4, 2024

 

 

2 Forward - Looking Statements This presentation and any accompanying oral presentation have been prepared by ADC Therapeutics SA ("ADC Therapeutics“, “we” or “us”) for informational purposes only and not for any other purpose. Nothing contained in this presentation is, or should be construed as, a recommendation, promise or representation by the presenter or ADC Therapeutics or any officer, director, employee, agent or advisor of ADC Therapeutics. This presentation does not purport to be all-inclusive or to contain all of the information you may desire. Information provided in this presentation an d a ny accompanying oral presentation speak only as of the date hereof. This presentation contains forward - looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. In some cases you can identify forward - looking statements by terminology such as “may”, “assumes”, “will”, “should”, “would”, “expect”, “intend”, “plan”, “anticipate”, “believe”, “estimate”, “predict”, “potential”, “seem”, “ see k”, “future”, “continue”, or “appear” or the negative of these terms or similar expressions, although not all forward - looking statements contain these identifying words. Forward - looking state ments are subject to certain risks and uncertainties that can cause actual results to differ materially from those described. Factors that may cause such differences include, but are not limited to: the actual Zynlonta revenue for 4Q 2023 , the success of the Company’s updated corporate strategy including operating efficiencies, capital deployment and portfolio prioritization; the expected cash runway into the beginning of Q4 2025, the effectiveness of th e new commercial go - to - market strategy, competition from new technologies, the Company’s ability to grow ZYNLONTA® revenue in the United States; Swedish Orphan Biovitrum AB (Sobi®) ability to successfully commercialize ZYNLONTA® in the European Economic Area and market acceptance, adequate reim bu rsement coverage, and future revenue from the same; approval by the NMPA of the BLA for ZYNLONTA® in China submitted by Overland ADCT BioPharma an d future revenue from the same, our strategic partners’, including Mitsubishi Tanabe Pharma Corporation, ability to obtain regulatory approval for ZYNLONTA® in foreign jurisdictions, and the timing and amount of futur e r evenue and payments to us from such partnerships; the timing and results of the Company’s or its partners’ research projects or clinical trials including early research in certain solid tumors with different targets, linke rs and payloads, LOTIS 5 and 7, ADCT 601 and 602 as well as IITs in FL and MZL, the timing and results of research the timing and outcome of regulatory submissions for the Company’s products or product candidates; actions by the FDA or fore ign regulatory authorities, the ability to complete clinical trials on expected timelines, if at all, and the results of the same; projected revenue and expenses; the Company’s indebtedness, including Healthcare Royalty Management and Blu e Owl and Oaktree facilities, and the restrictions imposed on the Company’s activities by such indebtedness, the ability to repay such indebtedness and the significant cash required to service such indebtedness; and the Com pany’s ability to obtain financial and other resources for its research, development, clinical, and commercial activities. Additional information concerning these and other factors that may cause actual results to differ mate ria lly from those anticipated in the forward - looking statements is contained in the “Risk Factors” section of the Company's Annual Report on Form 20 - F and in the Company's other periodic and current reports and filings with the U.S. Secur ities and Exchange Commission. These statements involve known and unknown risks, uncertainties and other factors that may cause actual results, performance, achievements or prospects to be materially different from any f utu re results, performance, achievements or prospects expressed in or implied by such forward - looking statements. The Company cautions investors not to place undue reliance on the forward - looking statements contained in this docum ent. Forward - looking statements are based on our management’s beliefs and assumptions and on information currently available to our m anagement. No assurance can be given that such future results will be achieved. Such forward - looking statements contained in this presentation speak only as of the date of this presentation. The Company expressly discl aim any obligation or undertaking to update these forward - looking statements contained in this presentation to reflect any change in our expectations or any change in events, conditions, or circumstances on which such st ate ments are based unless required to do so by applicable law. No representations or warranties (expressed or implied) are made about the accuracy of any such forward - looking statements. Certain information contained in this presentation relates to or is based on studies, publications, surveys, and other data d eri ved from third - party sources and our own internal estimates and research. While we believe these third - party sources to be reliable as of the date of this presentation, we have not independently verified, and we make no represen tat ion as to the adequacy, fairness, accuracy or completeness of, any information obtained from third - party sources. In addition, all of the market data included in this presentation involve a number of assumptions and limitati ons , and there can be no guarantee as to the accuracy or reliability of such assumptions. Finally, although we believe our own internal research is reliable, such research has not been verified by any independent source.

 

 

3 ADC Therapeutics at a Glance Solid Tumors Advancing ADCT - 601 targeting AXL in the clinic and multiple investigational ADCs Hematology Maximizing ZYNLONTA® in 3L+ DLBCL and expanding into earlier lines of DLBCL and indolent lymphomas; advancing ADCT - 602 targeting CD22 Corporate Cash runway into 4Q 2025 with multiple catalysts in 2024 Platform Pioneering ADC field with robust technology toolbox and specialized end - to - end capabilities ADC: Antibody Drug Conjugate; DLBCL: Diffuse Large B - Cell Lymphoma

 

 

4 Clinical Strong track record including an approved product with robust lifecycle management and multiple clinical assets Platform Validated and differentiated ADC platform with multiple payloads and targets Regulatory Proven capabilities securing FDA and EMA approvals for ZYNLONTA and multiple INDs Platform and Capabilities for Developing Optimized ADCs CMC: Chemistry, Manufacturing and Controls; PBD: Pyrrolobenzodiazepines Discovery Cutting - edge research to select the optimal targeting moiety, linker, and payload Development Swiftly moving from research to clinical trials with an optimized development strategy Manufacturing Robust in - house CMC capabilities enhanced by a top - tier external manufacturing network Commercialization Integrated go - to - market model with experienced team

 

 

5 2023: Positioning the Company for Success ▪ Management team with extensive commercial, development, and corporate expertise ▪ Board members with biotech and large pharma leadership experience; larger number of independents ▪ Established new go - to - market model with upgraded talent ▪ Refined brand positioning and enhanced data generation ▪ Hematology: ZYNLONTA Life Cycle Management, ADCT - 602 ▪ Solid tumors: ADCT - 601, multiple novel ADCs ▪ Advancing a range of payloads, linkers, and conjugation technologies against multiple targets ▪ Expanded internal capabilities to enable partnerships for early - stage assets ▪ Right - sized organizational structure; trimmed consulting and contractors ▪ Reduced 3rd party spending, optimized tax, and improved return on investments Upgraded Organization En hanced ZYNLONTA Commercialization Prioritized Portfolio Validated Research Platform Realized Cost Efficiencies

 

 

6 Key Business Updates DLT: Dose - Limiting Toxicity; MTD: Maximum Tolerated Dose. Note: Financials are unaudited. ▪ Balance sheet with ~$ 278.5M cash at end of FY 2023 ▪ Cash runway expected to extend into 4Q 2025 ; double - digit Opex reduction in 2023 compared to 2022 ▪ LOTIS - 7 (ZYNLONTA with bispecifics ): Cleared first dosing cohort with no DLT and early signs of efficacy ▪ LOTIS - 5 (ZYNLONTA with rituximab): Accelerated enrollment in 2023, over 2/3rd enrollment completed ▪ ADCT - 601 (Targeting AXL): R eached MTD and currently in dose optimization; e arly signs of anti - tumor activity in both monotherapy and in combination ▪ ADCT - 901 (Targeting KAAG1): Discontinuing due to limited signs of efficacy in dose escalation, reallocating capital to prioritized programs ▪ 4Q 2023 revenues expected to be ~$16.5M , a double - digit percentage increase compared to 3Q 2023 Pipeline Corporate ZYNLONTA (loncastuximab tesirine - lpyl)

 

 

7 Unlocking Value of Robust ADC Portfolio in Hematology and Solid Tumors DLBCL: Diffuse Large B - Cell Lymphoma; FL: Follicular Lymphoma; MZL: Marginal Zone Lymphoma; NSCLC: Non Small - Cell Lung Cancer; ALL: Acute Lymphoblastic Leukemia. Short - Mid Term Mid - long Term Hematology Portfolio Solid Tumor Portfolio ZYNLONTA ▪ Maximize ZYNLONTA in 3L+ DLBCL ▪ Seek to expand ZYNLONTA to earlier lines of DLBCL and other indolent lymphomas (e.g., FL, MZL) as single agent and combination agent of choice ‒ ZYNLONTA ‒ ZYNLONTA + rituximab (LOTIS - 5) ‒ ZYNLONTA + bispecifics (LOTIS - 7) ADCT - 602 (CD22) ▪ Escalating and expanding Phase 1 dose in r/r ALL ADCT - 601 (AXL) ▪ Optimizing dose for expansion as single agent and / or in combination in sarcoma, pancreatic, and NSCLC Next - generation ADCs ▪ Advancing a portfolio of investigational ADCs ‒ Differentiated exatecan - based payload with novel hydrophilic linker ‒ Targeting Claudin - 6, NaPi2b, PSMA ▪ Continuing research with a range of payloads, linkers, and conjugation technologies against undisclosed targets

 

 

8 Focused Pipeline in Hematology and Solid Tumors Anticipated milestones set forth in this chart are subject to further future adjustment. NTE: Non - Transplant Eligible. 1. DLBCL, FL, MZL 2. Non - selected advanced / metastatic NSCLC completed. Moving forward with AXL expressing NSCLC contingent on in - house IHC a ssay. AA: Accelerated Approval. Preclinical Phase 1a Phase 1b Phase 2 ZYNLONTA | Targeting CD19 ADCT - 602 | Targeting CD22 Expected Milestones LOTIS - 5: Complete enrollment in 2024 LOTIS - 7: Additional dose escalation/ expansion data in 2024 Phase 3 / Confirmatory Hematology Confirmatory LOTIS - 5 with rituximab in 2L+ NTE DLBCL LOTIS - 2 in 3L+ DLBCL NaPi2b Candidate selected FDA approved (AA) LOTIS - 7 in combination with glofitamab in r/r NHL 1 Solid Tumors Single agent and with gemcitabine in adv. / met. Sarcoma Mipasetamab uzoptirine ( ADCT - 601) | Targeting AXL Additional data from Phase 1 study in 2024 Acute Lymphoblastic Leukemia Additional data from Phase 1 study in 2024 Claudin - 6 PSMA Undisclosed target Candidate selection in 2024 Candidate selection in 2024 Candidate selection in 2024 Single agent and with gemcitabine and others in adv. / met. Pancreatic Single agent and other combinations in adv. / met. NSCLC 2 LOTIS - 7 in combination with mosunetuzumab in r/r NHL 1 Next - Gen ADCs | Exatecan Payload with Novel Linker

 

 

9 Proportion of patients by line - of - therapy* DLBCL, FL & MZL account for ~60% of mature B - cell lymphomas 1 * 1L (~70%) 1L (~65%) 1L (~61%) DLBCL FL MZL Key: Current Approval Current Development Areas Advancing ZYNLONTA Development in B - Cell Lymphomas 2L (~24%) 2L (~27%) 3L+ (~11%) 3L+ (~12%) 2023 U.S. Market Value 2 , 5 - year prevalence 3 ▪ LOTIS - 5 and LOTIS - 7 potential to move ZYNLONTA into 2L+ DLBCL Current Development Areas ▪ IIT suggests ZYNLONTA regimen could provide benefit in 2L+ high - risk FL (96% ORR, 85% CR, N=27); IIT studying ZYNLONTA in 2L+ MZL ‒ Unmet need is significant in these populations ‒ Assessing regulatory path and compendial strategy ▪ ZYNLONTA combination with bispecifics (LOTIS - 7) is currently being studied in r/r FL and r/r MZL $3.1b 2 , ~109 K patients $2.6b 2 , ~61 K patients $1.4b 2 , ~38 K patients 1. As per Leukemia & Lymphoma Society data; 2. Clarivate & Global Data used to size US market value; 3. Cerner Enviza CancerMPact database, 2023. Note: Distribution by line of therapy is based on the incident, drug - treated population .

 

 

10 ZYNLONTA: W ell - positioned to Lead in 3L/3L+ DLBCL with Product Profile Ideally Suited Across Treatment Settings Community Centers/ Hospitals Academic Centers PRODUCT PROFILE ▪ Off - the - shelf option for R/R patients with rapid, deep and durable single - agent efficacy ‒ Fast time to response (median 41 days) with no step - up dose required ‒ Median DoR not yet reached for patients in CR at 2 - year follow - up ▪ Manageable safety profile with no CRS, ideal for community care ▪ Simple dosing, with no REMS or inpatient stay requirements OPPORTUNITY ▪ For patients who will remain in community care and will not get to CAR - T or bispecifics ▪ For patients post CAR - T or bispecifics

 

 

11 ZYNLONTA in 3L+ DLBCL: Current and Forward Looking GtN : Gross - to - Net Implemented new commercial model focused on: ▪ Increasing / leveraging advocacy from the academic centers ▪ Growing community awareness and utilization, where the majority of the opportunity is for ZYNLONTA Rationale for change: ▪ Increasing competition in fragmented r/r DLBCL market particularly in the academic setting where complicated therapies are administered ▪ Increasing influence of academic centers to community and need for tighter coordination in local healthcare markets Impact of execution since implementation in August 2023: ▪ Average vials per day in November / December in line with 1H, partially offset by high single digit percentage point increase in GtN from 1H to 2H 2023 ▪ Increase in the number of accounts and volume from community ▪ Average calls per month back to 1Q 2023 level Increase Key Thought Leader Advocacy 1 Drive Awareness of ZYNLONTA’s Differentiated Profile 2 Ensure a Positive Patient Experience 3 STRATEGIC IMPERATIVES 2023 2024

 

 

12 BsAbs : Bispecific Antibodies; R : Rituximab ; ORR: Overall Response Rate; CR: Complete Response, REMS: Risk Evaluation and Mitigation Strategies, SCT: Stem - Cell Transplant ▪ ZYNLONTA combinations deliver simple dosing with no REMS ▪ ZYNLONTA combinations have potential to expand to 2L+ populations ‒ LOTIS - 5 (ZYNLONTA + R) results to date show 80% ORR and 50% CR in 2L+ SCT - ineligible DLBCL (N=20) ‒ Combos with bispecifics may elevate efficacy to levels of CAR - T , given high single agent activity of both drugs and non - overlapping toxicities (excluding neutropenia) ▪ ZYNLONTA combinations have the potential to deliver manageable safety profiles that are well - suited to both the academic and community settings ACCESSIBILITY EFFICACY SAFETY Potential for ZYNLONTA Combinations in 2L+ DLBCL

 

 

13 LOTIS - 5 Overview ▪ Patient Population: 2L+ DLBCL, ASCT ineligible ▪ Summary: Ph3 confirmatory trial in combination with rituximab ▪ Status: ‒ Enrollment ongoing in randomized portion, target 350 patients ‒ IDMC met in July 2023 and reviewed more than 100 pts , there were no safety concerns and recommended for the study to move forward as planned ▪ Support: Updated safety lead - in results at SOHO 2023: ORR of 80%, CR of 50% with no new safety signals ▪ Next steps: Enrollment expected to complete in 2024 Accelerated Enrollment in 2023 Q1 2022 Q2 2022 Q3 2022 Q4 2022 Q1 2023 Q2 2023 Q3 2023 Q4 2023 > 2/3 rd Pts Enrollment 2022 Enrollment 2023 Enrollment ~1.5X Pace LOTIS - 5: Developing ZYNLONTA to be the Combination Agent of Choice in Earlier Lines of Therapy Target Positioning Competitive 2L+ efficacy with favorable safety and convenient dosing schedule, well - suited for use in both academic and community settings

 

 

14 Arm E Arm F Treatment Period (cycles of 21 days) r/r DLBCL, FL, MZL for both arms May include r/r DLBCL, FL, and MZL ZYNLONTA will be given at RD for the specific combinations and subpopulations determined in part 1 End of Treatment Part 1 3+3 Dose escalation (ZYNLONTA 90, 120, and 150 μg /kg) Part 2 Dose expansion Screening Period (≤28 d) Mosunetuzumab + escalating doses of ZYNLONTA Q3W 2 Enrollment began July 2023 Glofitamab + escalating doses of ZYNLONTA Q3W 1 Enrollment began July 2023 1. Obinutuzumab pretreatment 1000mg on C1D1; ZYNLONTA administered on C1D2; administration of 1 st and 2 nd step - up dose(s) of IV glofitamab (2.5mg on C1D8 & 10mg on C1D15); ZYNLONTA plus glofitamab 30mg on C2D1 and beyond (reduce ZYNLONTA to 75 ug/kg at C3 if starting dose is 120 ug/kg or higher) 2. ZYNLONTA plus subcutaneous mosunetuzumab 1st step - up dose of 5 mg on C1D1, followed by mosunetuzumab 2nd step - up & target dose of 45 mg for C1D8 & C1D15; ZYNLONTA plus 45mg of subcutaneous mosunetuzumab on C2D1 and beyond (reduce ZYNLONTA to 75 μg /kg at C3 if starting dose is 120 ug/kg or higher) LOTIS - 7: Combining ZYNLONTA with Bispecific Antibodies ( Glofitamab or Mosunetuzumab ) ENDPOINTS ▪ Primary: Safety and tolerability; MTD and/or RD ▪ Secondary: Efficacy: ORR, DOR, CRR, PFS, RFS, OS; Pharmacokinetics and Immunogenicity STUDY POPULATION ▪ Relapsed or Refractory B - NHL patients and have received: Part 1: >2 systemic treatment regimens; Part 2: >1 systemic treatment regimens ▪ Prior autologous SCT (>100 days) or CAR - T (>30 days) is allowed RATIONALE ▪ Distinct MOAs and non - overlapping toxicities, except neutropenia ▪ Most potent off - the - shelf, single agent drugs approved in DLBCL ▪ ZYNLONTA use prior to glofitamab may debulk the tumors and reduce peripheral B cells, leading to lower CRS rates

 

 

15 IIT on FL Note: 1 Data as of December 21, 2023. MOA: Mechanism of Action; CRS: Cytokine Release Syndrome LOTIS - 7: Preliminary Results and Next Steps Expecting additional data to be shared in 2024 NEXT STEPS ▪ Expect to continue dose escalation up to 150 µg/kg ▪ In parallel, expect to expand in 120 µg/kg with glofitamab in DLBCL once the DLT period has been cleared ▪ Plan to expand to other dosing cohorts in 3L+ and move to expansion in 2L+ ▪ Adding multiple new sites to accelerate enrollment EARLY SAFETY UPDATES (DL1) ▪ DLT period has been cleared for DL1 (90 µg/kg ZYNLONTA) in both arms (+ glofitamab and + mosunetuzumab ) ▪ No cases of CRS in the glofitamab arm, Grade 1 CRS (fever only) observed in the mosunetuzumab arm ▪ No discontinuations due to AEs EARLY EFFICACY UPDATE (DL1) ▪ To date, each of the first five patients eligible for assessment in this dosing level has shown response (PR or CR) at first scan

 

 

16 ZYNLONTA + Rituximab Showed Strong Initial Signals in High - risk r/r FL with 96% ORR and 85% CR rates Patient Population – 2L+ FL U of Miami IIT in FL - ASH 2023 Oral Presentation 1L 1L Phase 2 study of loncastuximab tesirine with rituximab in patients with high - risk relapsed/refractory follicular lymphoma. Highlights of the data presented at ASH include: ▪ N = 33 patients enrolled out of a targeted 39, 27 patients evaluable for efficacy and 32 patients evaluable for toxicity ▪ Best overall response rate of 96% and CR rate of 85% ▪ After a median follow - up of 9.7 months, the median progression - free survival (PFS) was not reached, and the 12 - month PFS was 92% ▪ Majority of adverse events (AEs) were grade 1. Grade 3 AEs included neutropenia (n=2; 6%), and one case each (3%) of hyperglycemia, increased ALT, fatigue, dyspnea and skin infection. Neutropenia was the only grade 4 AE (n=1; 3%) 1.Ghione et al., Blood (2022); 2.Salles et al., Blood Adv (2022); 3. Budde E, et al. Lancet Oncol, 2022; 4. Sehn L, et al. Lancet Oncol 2016; 17: 1081 – 93 ; 5. Leonard J, et al. J Clin Oncol, 2019 37:1188 - 1199; 6. Cerner Enviza CancerMPact database, 2023 Note: Distribution by line of therapy is based on the incident, drug - treated population . 0 - 100 - 90 - 70 - OR R Len + Rituximab (R2) (2L+) 5 78% Benda + Obin (2L+) 4 79% % 80 - Mosun label (3L+) 3 80% 0 - 100 - 80 - CR Mosun label (3L+) 3 60% Benda + Obin (2L+) 4 17% Len + Rituximab (R2) (2L+) 5 34% % 60 - 40 - 20 - Current r/r FL Competitive Landscape ~21 K 2L+ FL patients U.S. 5 - year Prevalence 6 3L+ Key: 2L 1L ▪ University of Miami plans to expand the number of trial participants up to 100 and add other cancer research centers ▪ Data is expected to be published at a medical conference ▪ Path forward will be discussed with regulatory authorities and compendia Next Steps Axi - cel (3L+) 1 94% Axi - cel (3L+) 1 Tisa - cel (3L+) 2 69% Tisa - cel (3L+) 2 86% 79%

 

 

17 ZYNLONTA has Potential to Address Significant Unmet Need in MZL Given Low CR Rates with Approved Therapies 1. Sehn L, et al. Lancet Oncol 2016; 17: 1081 – 93. 2. Opat S, et.al - ASH Oral Presentation December 2022, New Orleans, LA. 3. Leonard J, et al. J Clin Oncol, 2019 37:1188 - 1199. 4. Cerner Enviza CancerMPact database, 2023. Note: Distribution by line of therapy is based on the incident, drug - treated population . 1L 1L ▪ It is expected that the futility analysis for this study will have 19 patients and it will be conducted in the first half of 2024. The investigator plans to share the results at an upcoming scientific congress ▪ University of Miami plans to add other cancer research centers in order to accelerate enrollment of up to 50 trial participants ▪ Study Title: A Phase 2, Open - label, Study Evaluating Safety and Efficacy of the Loncastuximab in Relapsed/Refractory Marginal Zone Lymphoma ▪ Line of Therapy: Relapsed/Refractory ▪ Status: 15 patients enrolled as of December 2023 U of Miami IIT in MZL Overview Next Steps 0 - 80 - OR R Benda + Obin (2L+) 1 Zanubritinib (2L+) 2 68% % 79% 60 - Len + Rituximab (R2) (2L+) 3 64% 0 - 30 - CR % 20 - Len + Rituximab (R2) (2L+) 3 29% 10 - Current r/r MZL Competitive Landscape 40 - 20 - Zanubritinib (2L+) 2 26% Benda + Obin (2L+) 1 17% Patient Population – 2L+ MZL ~15 K 2L+ MZL patients U.S. 5 - year Prevalence 4 3L+ Key: 2L 1L

 

 

18 ADCT - 601: A Novel, Potent Approach to Targeting AXL Note: 1. GlycoConnect and HydraSpace are technologies licensed from Synaffix ; TI: therapeutic index; MTD: maximal tolerated dose; GlcNax : N - acetyl - glucosamine; GalNac : N - acetylgalactosamine ; SP: Spacer; PBD: Pyrrolobenzodiazepine . Source: Zammarchi et al., Mol Cancer Ther (2022) ADCT - 601 Structure Anticipated Differentiation ▪ Potential best - in - class ADC against a target expressed across multiple solid tumor types with unmet medical needs ▪ First AXL - targeted ADC conjugated to a PBD dimer cytotoxin ▪ Glycoconnect Ρ ,1 and Hydraspace Ρ ,1 technology enhance the TI of ADCT - 601 three - fold in preclinical models compared to ADCs manufactured by random stochastic conjugation PBD Sp Gal Nac Fuc HydraSpace Ρ cleavable linker and SG3199 (PBD dimer cytotoxin) Anti - human AXL antibody Antibody Linker + payload ADCT - 601 MOA Warhead released after internalization, and binds in minor groove of DNA ▪ PBD dimer creates interstrand cross - links ▪ No DNA distortion ▪ Avoids DNA repair mechanism ADCT - 601

 

 

19 ADCT - 601 Phase 1 Trial Design Note: 1 Sarcoma indications can include any from the following categories - soft tissue sarcoma (leiomyosarcoma, liposarcoma, undiffere ntiated pleomorphic sarcoma (UPS; covering malignant fibrous histiocytoma) and synovial sarcoma) or bone sarcoma ( ewing's sarcoma (including extraskeletal ), osteosarcoma, and chondrosarcoma). 2 Only 1 patient enrolled with cervical neuroendocrine carcinoma. MID: Maximum Investigated Dose. PoC: Proof of Concept. ADCT - 601 MONOTHERAPY Advanced/metastatic AXL Expressing NSCLC Advanced/metastatic Pancreatic Cancer Advanced/metastatic Tissue Sarcoma Part 2: Dose Optimization/Expansion Prioritized Indications Indications Tested Advanced/ metastatic NSCLC Any solid tumors with AXL amplification 2 Advanced/metastatic Sarcoma indications 1 ▪ 7.5 mg ​ ▪ 11 mg​ ▪ 13 mg (Dose / schedule optimization ongoing)​ ▪ 15 mg (MID) Doses Tested Part 1: 3+3 Dose Escalation – Ongoing ▪ 3.8 mg 601 +1000 mg/m Gem ▪ 11 mg 601 + 1000mg/m Gem ▪ 7.5 mg 601 +1000 mg/m Gem ▪ 11 mg 601 + 800mg/m Gem ▪ 13 mg 601 +1000 mg/m Gem ▪ 13 mg 601 + 800mg/m Gem Advanced/metastatic Sarcoma indications 1 Advanced/metastatic Sarcoma indications 1 Advanced/metastatic Pancreatic Cancer ADCT - 601 WITH GEMCITABINE Key : High AXL expression within a small indication (PoC) Moderate AXL expression within a large indication Subpopulation with high AXL expression within a large indication

 

 

20 ADCT - 601 Early Safety Results in Advanced / Metastatic Sarcoma Safety – ADCT - 601 Monotherapy ( STS ) Total (N=18) N (%) Any TEAE ≥ Gr3 9 (50.0) Total Discontinued (%) Discontinuation due to Treatment (%) 15 (83.3%) 3 (16.7) Preferred Term Any TEAE ≥ Gr3 (%) Cheilitis 1 (5.6) Abdominal pain 1 (5.6) Drug - induced liver injury 1 (5.6) Dyspnoea 1 (5.6) Eczema 1 (5.6) Generalized oedema 1 (5.6) Oedema peripheral 1 (5.6) Pulmonary embolism 1 (5.6) Thrombocytopenia 1 (5.6) Skin infections 1 (5.6) Photosensitivity reactions 1 (5.6) Lymphoedema 1 (5.6) LFT increased 1 (5.6) Hypotension 1 (5.6) Alanine aminotransferase increased 1 (5.6) Aspartate aminotransferase increased 1 (5.6) Gamma - glutamyltransferase increased 2 (11.1) Pleural effusion 1 (5.6) Uncoded 1 (5.6) Safety – ADCT - 601 With Gemcitabine (Sarcoma) Total (N=9) N (%) Any TEAE ≥ Gr3 8 (88.9) Total Discontinued (%) Discontinuation due to Treatment (%) 9 (100) 0 Preferred Term Any TEAE ≥ Gr3 (%) Anaemia 4 (44.4) Pleural effusion 2 (22.2) Thrombocytopenia 4 (44.4) Alanine aminotransferase increased 1 (11.1) Neutropenia 3 (33.3) Neutrophil count decreased 3 (33.3) Platelet count decreased 2 (22.2) Gamma - glutamyltransferase increased 2 (22.2) Arthralgia 1 (11.1) Aspartate aminotransferase increased 1 (11.1) Fatigue 1 (11.1) Hypertension 1 (11.1) Pleuritic pain 1 (11.1) Pneumonia 1 (11.1) Note: Data as of 12/04/2023. The data captured includes individual patients who experienced multiple AEs while on study.

 

 

21 ADCT - 601 Shows Early Signs of Anti - Tumor Activity as Monotherapy and in Combination in Sarcoma Patients Note: Data as of 12/04/2023. STS: Soft Tissue Sarcoma; NSCLC: Non - small cell lung cancer. ADCT - 601 Monotherapy (STS) -60% -50% -40% -30% -20% -10% 0% 10% 20% 30% 40% Baseline Week 6 Week 12 Week 21 15mg 13mg 11mg 7.5mg ADCT - 601 + Gemcitabine (Sarcoma) -60% -50% -40% -30% -20% -10% 0% 10% 20% 30% 40% 50% 60% Baseline Week 6 Week 12 Week 21 Week 30 Week 39 Week 48 % Change in Tumor Size 11mg 7.5 mg 3.8 mg Dose and schedule optimization at 13 mg initiated in STS and planned in Pancreatic cancer; dose expansion in NSCLC contingent on assay development Dose optimization in combination with gemcitabine planned in Sarcoma and Pancreatic cancer Change in Tumor Size Over Time Change in Tumor Size Over Time PR PR PR PR

 

 

22 A Growing Toolbox with a Range of Payloads, Linkers and Conjugation Technologies Note: 1 DAR: Drug antibody ratio Antibody ▪ Extensive experience identifying and advancing compelling targets with high unmet need ▪ Focus on masking binding, conditional binding moieties, bispecifics and biparatropics Linker ▪ Proprietary linkers that enable increased plasma stability and controlled payload release with tunable DAR 1 ‒ Cleavable linkers ‒ Reducible linkers ‒ Non - cleavable linkers Payload ▪ Forged next - gen PBDs as novel warheads; first to bring PBD ADC from conception to market ▪ Advancing next - gen payloads to improve selectivity, potency, therapeutic index ‒ Camptothecin derivatives ‒ DNA damaging agents ‒ Immunomodulators ‒ Dual payloads Conjugation Technology ▪ Technologies enabling precise site - specific attachment of diverse payloads ‒ Orthogonal conjugation approaches

 

 

23 Exatecan has the Potential to be Differentiated over Commercial - Stage Toxins such as DXd Note: 1 PgP : P - glycoprotein; 2 Cell line derived xenograft (CDX) model is a renal leiomyoblastoma model, a ll arms dosed intravenously qdx1 Source: Weng et al., Cancer Discov (2023) EXATECAN V. DXD ▪ Better potency ▪ No PgP 1 transport, enabling enhanced intracellular presence ▪ Increased bystander effect , leading to more cell death and enhancing therapeutic impact over DXd Exatecan DXd Vehicle Isotype (10 mg/kg) Antibody - D Xd (15 mg/kg) Antibody - exatecan (6.6 mg/kg) Antibody - exatecan (10 mg/kg) ▪ ADCT has developed a novel hydrophilic linker that enables efficient conjugation of exatecan ▪ Our exatecan - based ADCs enable traceless release of exatecan after internalization ▪ Superior therapeutic index driven by strong in vivo efficacy and excellent tolerability in cynomolgus monkey without any signs of ILD EXATECAN ADC V. DXD ADC in CDX MODEL 2 EXATECAN ADVANTAGE ADC THERAPEUTICS PLATFORM ADVANTAGE

 

 

24 Target description Phosphate transporter Adhesion protein Enzymatic glycoprotein Amino acid transporter Tumor types of interest NSCLC Ovarian cancer Ovarian cancer Endometrial cancer Prostate cancer NSCLC Colorectal cancer Payload Exatecan Exatecan Exatecan Exatecan Validation data in vitro characterization in vivo efficacy NHP toxicology in vitro characterization in vivo efficacy NHP toxicology Ongoing in vitro characterization in vivo efficacy NHP toxicology 2 Candidate selection 1 Complete 2024 2024 2024 Advancing ADC Assets Against Validated Targets in Indications with High Unmet Need Note: 1 IND enabling studies can be completed within 18 months after selection of the candidate ; 2 NHP study done with chimeric candidate NaPi2b Claudin - 6 PSMA Undisclosed target

 

 

25 Corporate Business Development Strategy for ADCT Portfolio HEMATOLOGY ZYNLONTA, ADCT - 602 SOLID TUMOR S ADCT - 601, Research Assets Business Development to Unlock Value Business Development Goals: U.S. EX - U.S. Co - development & Co - promote* Royalty & Milestones to ADCT Accelerate & Expand Asset Development 3 Non - dilutive Financing 2 Maximize Deal Value & Value Split 1 Direct Partnership *Flexible for alternative construct depending on economics. OVERLAND JOINT VENTURE

 

 

26 Cash Runway to Support Multiple Potential Near - Term Value - Driving Catalysts □ ZYNLONTA: □ Achieve commercial brand profitability in 2024 □ LOTIS - 5: Complete enrollment in 2024 □ LOTIS - 7: Dose escalation and expansion updates throughout 2024 □ FL and MZL IITs: Updates at medical conferences in 2024 / 2025 □ ADCT - 602 (CD22): Additional data updates from Phase 1 study in 2024 ▪ Exploring potential partnerships and licensing agreements ▪ Cash runway to 4Q 2025 to support company through value - generating milestones* Hematology □ ADCT - 601 (AXL): Additional data updates from Phase 1 study in sarcoma, pancreatic and NSCLC throughout 2024 □ Preclinical: Advancing a portfolio of investigational ADCs Solid Tumors * Cash runway assumes receipt of anticipated regulatory milestone payments under the Company’s collaboration agreements and use of the amount it is required to maintain under its loan agreement