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LOTIS-7 Clinical Trial Update December 11, 2024
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2 Today’s Speakers 02 LOTIS-7 Clinical UpdateMohamed Zaki Chief Medical Officer 01 ZYNLONTA Overview Ameet Mallik Chief Executive Officer Q&A03
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3 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 pres enter 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 and any 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”, “will”, “should”, “would”, “expect”, “intend”, “plan”, “anticipate”, “b elieve”, “estimate”, “predict”, “potential”, “seem”, “seek”, “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 statements are subject to certain risks and uncertainties that can cause actual results to differ materially from those described. Facto rs that may cause such differences include, but are not limited to: plans and timelines for the clinical development for LOTIS-7, including the therapeutic potential, clinical benefits and safety thereo f; uncertainty whether future data will be consistent with the preliminary data; expectations regarding timing, success and future data announcements for LOTIS -7; the expected cash runway into mid-2026; the Company’s ability to grow ZYNLONTA® revenue in the United States; the ability of our partners to commercialize ZYNLONTA in foreign markets, the timing and amount of future revenue and payments to us from such partnerships and their ability to obtain regulatory approval for ZYNLONTA® in foreign jurisdictions; the impact, if any, from the discontinuat ion of the ADCT 601; the timing, enrollment, and results of the Company’s or its partners’ clinical trials including LOTIS 5 and 7 as well as ADCT 602; the timing, results and publication of investig ator-initiated trials including those studying FL and MZL and the potential regulatory and/or compendia strategy and the future opportunity; the timing and results of the Company’s research and develop ment in solid tumors with different targets, linkers and payloads including the Company’s exatecan based platform; the timing and outcome of regulatory submissions for the Company’s products or product candidates; actions by the FDA or foreign regulatory authorities; projected revenue and expenses; the Company’s indebtedness, including Healthcare Royalty Management and Blue Owl and Oaktree facilities, and the restrictions imposed on the Company’s activities by such indebtedness, the ability to comply with the terms of the various agreements and repay such inde btedness and the significant cash required to service such indebtedness; and the Company’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 materially from those anticipated in the forward -looking statements is contained in the “Risk Factors” section of the Company's Annual Report on Form 10-K and in the Company's other periodic and current reports and filings with the U.S. Securities and Exchange Commissio n. These statements involve known and unknown risks, uncertainties and other factors that may cause actual results, performance, achievements or prospects to be materially differ ent from any future 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 fo rward-looking statements contained in this document. Forward-looking statements are based on our management’s beliefs and assumptions and on information currently available to our management. 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 disclaim 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, con ditions, or circumstances on which such statements 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 derived 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 representation 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 limitations, 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.
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4 CORPORATE ❑ ZYNLONTA Strategy and LOTIS-7 Overview ❑ ZYNLONTA LOTIS-7 Initial Trial Results ❑ ZYNLONTA Growth Potential Agenda
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5 CORPORATE Initial Readout of ZYNLONTA Combination with Glofitamab ZYNLONTA is currently approved with multiple opportunities to expand usage in B-NHL Studying combination of two potent, FDA approved single agent drugs in DLBCL: ZYNLONTA & glofitamab (COLUMVITM) Promising initial data show best ORR of 94% (17/18 pts) and CR rate of 72% (13/18 pts) as of November 20, 2024 cutoff date Combination is generally well tolerated with no DLTs across all dose levels based on initial data (n=29) potentially enabling use across care settings
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6 Advancing ZYNLONTA Development into 2L+ B-Cell Lymphomas Current Approval Current Development Areas DLBCL FL MZL 1L 2L+ 3L+ ZYNLONTA+R ZYNLONTA ZYNLONTA+R ZYNLONTA ZYNLONTA PHASE 2 IIT DATA PRESENTED AT ASH 2024 SUGGEST POTENTIAL BENEFIT IN INDOLENT LYMPHOMAS → ZYNLONTA + rituximab in high-risk r/r FL1: 97% ORR, 77% CR, n=35 → ZYNLONTA monotherapy in r/r MZL2: 91% ORR, 70% CR, n=23 1 As detailed in ASH 2024 oral presentation; 2 As detailed in ASH 2024 poster. LOTIS-5 LOTIS-7 POTENTIAL TO MOVE INTO 2L+ DLBCL → LOTIS-5 (ZYNLONTA + rituximab): 20 patient safety run-in data showing ORR of 80%, CR of 50% with no new safety signals, complete enrollment in 2024 → LOTIS-7 (ZYNLONTA + bispecific): Promising initial efficacy data with 94% best ORR and 72% CR rate (n=18) with manageable safety profile (n=29)
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7 CORPORATE DLBCL Treatment: Paradigm and Epidemiology 1L ~30k Patients 2L ~12k Patients 3L+ ~6k Patients R-CHOP Pola + R-CHP CAR-T BsAbs Glofitamab Epcoritamab ZYNLONTA Pola-BR R-Based Chemo R-Based ChemoPola-BRSalvage +/- ASCT Cell Therapy ChemoADCs / mAbsBispecificsTREATMENT OPTION : • ZYNLONTA + rituximab and bispecific antibody-based therapies expected to move to 2L by 2026 if approved • Polatuzumab usage continues to increase in 1L; retreatment in subsequent lines less likely • CAR-T use limited to authorized centers with significant logistical and safety barriers • Chemotherapy use persists despite limited durability and some irreversible toxicities LOTIS-7 Patient Population Salvage +/- ASCT This illustration is not exhaustive and does not include all FDA approved therapies CAR-T Tafa + Len Tafa + Len
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8 ZYNLONTA Combinations in Highest Growth r/r DLBCL Modalities Potential for highly competitive efficacy with better safety and accessibility Projected Trend 1 2L+ DLBCL Market Dynamics* Cell Therapy Chemo ADCs / mAbs Bispecifics Efficacy Potential to raise the bar for efficacy in this class with competitive safety and accessibility → Emerging ADC and bispecific combinations with improved clinical profiles have the potential to reduce chemotherapy and cell therapy use → Efficacy approaching CAR-T levels with manageable safety enabling use across care settings, with potential to disrupt treatment paradigm ZYNLONTA LOTIS 7 ZYNLONTA LOTIS 5 *Based on internal review of approved labels for existing modalities; Efficacy refers to rapid, deep, and durable responses. Safety refers to manageable and reversible toxicities. Accessibility refers to availability across treatment settings; 1. Putnam Research & Analysis of 150 physicians (Q3 2024). Share Accessibility Safety
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9 CORPORATE LOTIS-7 Combination Rationale and Biological Hypothesis Potent, approved single agent drugs with distinct and complementary MOAs EFFICACY ❑ Expected to have additive or synergistic efficacy SAFETY ❑ No overlapping non-hematologic toxicities expected to yield manageable safety profile ❑ Potentially lower CRS rates/grades given ZYNLONTA use prior to glofitamab may debulk the tumors and reduce peripheral B cells ZYNLONTA ANTI-CD19 ADC GLOFITAMAB ANTI-CD20/CD3 T-CELL ENGAGING BISPECIFIC ANTIBODY
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10 Arm EArm F Treatment Period (cycles of 21 days) r/r DLBCL, FL, MZL for both arms r/r DLBCL ZYNLONTA IV (120 or 150 µg/kg3) + glofitamab IV Q3W Enrollment initiated Apr 2024 End of Treatment Part 1 3+3 Dose escalation (ZYNLONTA 90, 120, and 150 µg/kg) Part 2 Dose expansion Screening Period (≤28 d) Escalating doses of ZYNLONTA IV + mosunetuzumab SC Q3W2 Enrollment began July 2023 Escalating doses of ZYNLONTA IV + glofitamab IV Q3W1 Enrollment began July 2023 1. Obinutuzumab pretreatment 1000mg on C1D1;ZYNLONTA administered on C1D2; administration of 1st and 2nd 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) 3. ZYNLONTA dose reduced to 75 μg/kg at C3 LOTIS-7: Phase 1b Trial of ZYNLONTA in Combination with Glofitamab Endpoints ▪ Primary: Safety and tolerability; MTD and/or RD ▪ Secondary: o Efficacy: ORR, DOR, CRR, PFS, RFS, OS o Pharmacokinetics and Immunogenicity Study Population ▪ Relapsed or Refractory B-NHL patients, ECOG PS 0 – 2, and have received: o Part 1: >2 systemic treatment regimens o Part 2: >1 systemic treatment regimens ▪ Prior autologous SCT or CAR-T (>100 days) is allowed ▪ Measurable disease per 2014 Lugano Classification ▪ Excludes patients with clinically significant 3rd space fluid accumulation ZYNLONTA + Glofitamab Treatment Sequence Trial Status ▪ Dose escalation complete with no DLTs, no high-grade CRS or ICANS and early signs of anti-tumor activity ▪ Dose expansion ongoing in ZYNLONTA (120 or 150 µg/kg) + glofitamab with 20 patients planned for each dosing cohort
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11 LOTIS-7 Clinical Trial: Initial Safety and Efficacy Results As of data cutoff of November 20, 2024 Best overall response data in 18 evaluable patients (Parts 1 & 2) shows ORR of 94% (17/18 pts) and CR rate of 72% (13/18 pts) – 12/13 patients with CR remain in CR as of the data cut-off – 5 patients converted from SD/PR to CR over time – Encouraging efficacy data was observed across patients with different numbers of lines and types of prior treatments and across different histologies Safety data on all 29 evaluable patients show the combination is generally well tolerated with a manageable safety profile and no DLTs across all dose levels – TEAEs of Grade 3* or higher occurring in ≥ 5% of patients included neutropenia (24%), lymphopenia (7%) and hypokalemia (7%) – No high-grade CRS or ICANS observed across Parts 1 and 2 – No Grade 5 TEAEs were reported Note: Data extracted from live clinical database. Data is subject to change. * Based on American Society for Transplantation and Cellular Therapy (ASTCT) guidelines Early efficacy data supports the combination of ZYNLONTA with glofitamab in 2L+ DLBCL Initial data suggest combination of ZYNLONTA + glofitamab has a manageable safety profile in r/r B-NHL
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12 CORPORATE Agenda ❑ ZYNLONTA Strategy and LOTIS-7 Overview ❑ ZYNLONTA LOTIS-7 Trial Results ❑ ZYNLONTA Growth Potential
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13 LOTIS-7 Phase 1b Trial: Patient Population ZYNLONTA plus glofitamab Part 1 Part 2 Total Safety Evaluable Population* r/r Non-Hodgkin Lymphoma N = 9 N = 20 N = 29 Efficacy Evaluable Population** r/r Diffuse Large B-cell Lymphoma N= 1 @ 120 µg/kg N= 2 @ 150 µg/kg Total = 3 N=8 @ 120 µg/kg N=7 @ 150 µg/kg Total = 15 N=9 @ 120 µg/kg N=9 @ 150 µg/kg Total = 18 * Safety Evaluable Population: patients with at least one dose of lonca in database ** Efficacy Evaluable Population: measurable disease at study entry, at least one dose of investigational product, at least one post baseline assessment PET/ CT Data cutoff: 20 Nov 2024. Note: Data extracted from live clinical database. Data is subject to change.
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14 CORPORATE LOTIS-7 Phase 1b Trial: Baseline Patient Characteristics Safety Population (N=29) as of November 20, 2024 N=29 Ann Arbor stage I/II 5 (17.2%) III/IV 23 (79.3%) missing 1 (3.4%) Bulky disease >6 cm 7 (24.2%) >10 cm 1 (3.4%) Median prior lines of therapy (range) 2 (1,5) Number of prior lines of therapy 1 11 (37.9%) ≥2 18 (62.1%) Prior CAR-T Therapy 7 (24.1%) Refractory to primary therapy 15 (51.7%) Refractory to last prior therapy 18 (62.1%) N=29 Median age [years (range)] 73 (26,88) Male 20 (69%) ECOG Performance Status 0 17 (58.6%) 1 12 (41.4%) 2 0 LBCL Histology DLBCL 14 (48.3%) trFL 6 (20.7%) HGBCL 4 (13.8%) FL Grade 3b 1 (3.4%) Indolent Histology FL 3 (10.3%) MZL 1 (3.4%) IPI Score 0/1/2 15 (51.7%) 3/4/5 14 (48.3%) LBCL = large B-cell lymphoma, DLBCL= diffuse large B-cell lymphoma, HGBCL= high grade B-cell lymphoma, trFL= transformed follicular lymphoma, FL= follicular lymphoma, MZL=marginal zone lymphoma Data cutoff: 20 Nov 2024 Note: Data extracted from live clinical database. Data is subject to change.
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15 CORPORATE LOTIS-7 Phase 1b Trial: Safety Summary Safety Population (N=29) as of November 20, 2024 *As per Investigator reported adverse events TEAE = treatment emergent adverse event, AESI = adverse event of special interest Data cutoff: 20 Nov 2024. Data extracted from live clinical database. Data is subject to change. 90 µg/kg n=3 120 µg/kg n=13 150 µg/kg n=13 All n = 29 Grade 3/4 TEAEs (≥ 5% of patients) * 2 (66.7%) 8 (61.5%) 6 (42.2%) 16 (55.2%) Neutropenia 1 (33.3%) 2 (15.4%) 4 (30.8%) 7 (24.1%) Lymphopenia 1 (33%) 1 (7.7%) 0 2 (6.9%) Hypokalemia 0 2 (15.4) 0 2 (6.9%) Grade 3/4 AESI (all patients) * Febrile neutropenia 0 0 1 (7.7%) 1 (3.4%) Thrombocytopenia 0 0 1 (7.7%) 1 (3.4%) GGT increase 0 1 (7.7%) 0 1 (3.4%) Generalized oedema 0 1 (7.7%) 0 1 (3.4%) Rash 0 1 (7.7%) 0 1 (3.4%) Photosensitivity reaction 0 0 1 (7.7 %) 1 (3.4%) Sepsis 0 1 (7.7%) 0 1 (3.4%) Upper respiratory infection 0 1 (7.7%) 0 1 (3.4%) Pneumonia 0 1 (7.7%) 0 1 (3.4%) TEAEs leading to study drug discontinuation (one or both drugs discontinued)* ICANS (glofitamab only discontinued) 0 1 (33%) 0 1 (3.4%) Pericardial effusion (loncastuximab only discontinued) 0 0 1 (33%) 1 (3.4%) Pleural effusion (loncastuximab and glofitamab both discontinued) 1 (33%) 0 0 1 (3.4%)
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16 CORPORATE LOTIS-7 Phase 1b Trial: CRS/ICANS Profile & Management Safety Population (N=29) as of November 20, 2024 * Number of patients who experienced at least 1 event per ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells; worst grade reported if applicable Data Cutoff 20 Nov2024. Note: Data extracted from live clinical database. Data is subject to change. 90 µg/kg n=3 120 µg/kg n=13 150 µg/kg n=13 All n = 29 Cytokine Release Syndrome* Any grade 0 6 (46.2%) 4 (30.8%) 10 (34.5%) Grade 1 0 5 (38.5%) 3 (23.1%) 8 (27.6%) Grade 2 0 1 (7.7%) 1 (7.7%) 2 (6.9%) Grade >3 0 0 0 0 ICANS* Any grade 0 1 (7.7%) 1 (7.7%) 2 (6.9%) Grade 1 0 0 0 0 Grade 2 0 1 (7.7%) 1 (7.7%) 2 (6.9%) Grade > 3 0 0 0 0 • CRS cases managed with tocilizumab, corticosteroids, acetaminophen, and/or fluid bolus • No requirement for ICU admittance or pressor support • Both patients with ICANS had complete resolution of symptoms • One patient resumed treatment and ultimately achieved a CR; one patient elected to discontinue treatment • ICANS managed primarily with corticosteroids in both patients
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17 CORPORATE LOTIS-7 Phase 1b Trial: Baseline Patient Characteristics Efficacy Evaluable Population (N=18) as of November 20, 2024 N=18 Ann Arbor stage I/II 3 (16.7%) III/IV 15 (83.3%) Bulky disease >6 cm 6 (33.3%) >10 cm 1 (5.6%) Median prior lines of therapy (range) 2 (1,5) Number of prior lines of therapy 1 5 (27.8%) ≥2 13 (72.2%) Prior CAR-T Therapy 5 (27.8%) Refractory to primary therapy 9 (50.0%) Refractory to last prior therapy 9 (50.0%) N=18 Median age [years (range)] 72 (26,82) Male 13 (72.2%) ECOG Performance Status 0 12 (66.7%) 1 6 (33.3%) 2 0 (0%) Histology DLBCL 10 (55.6%) HGBCL 3 (16.7%) trFL 4 (22.2%) FL Grade 3b 1 (5.6%) IPI Score 0/1/2 9 (50.0%) 3/4/5 9 (50.0%) Data cutoff 20 Nov 2024. Note: Data extracted from live clinical database. Data is subject to change.
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18 120 µg/kg 150 µg/kg Total n=9 % n=9 % n=18 % ORR (CR + PR) 8 89% 9 100% 17 94% Complete Response (CR) 6 67% 7 78% 13 72% Partial Response (PR) 2 22% 2 22% 4 22% Stable Disease 1 11% 0 0% 1 6% Progressive Disease 0 0% 0 0% 0 0% As of data cut off 20 Nov 2024. Note: Data extracted from live clinical database. Data is subject to change. LOTIS-7 Phase 1b Trial: Best Overall Response Efficacy Evaluable Population (N=18) as of November 20, 2024
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19 • 12/13 CRs remain in CR as of the data cut-off • Most responses observed at initial assessment • 5 patients converted from SD/PR to CR over time 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 Dose Level 120 µg/kg Patients Dose Level 150 µg/kg Patients Not Efficacy Evaluable Patients (4 patients have not yet reached the 6-week assessment; 1 patient withdrew prior to any assessment) As of data cut off 20 Nov 2024. Note: Data extracted from live clinical database. Data is subject to change. LOTIS-7 Phase 1b Trial: Best Overall Response Efficacy Evaluable Population (N=18) as of November 20, 2024 X X End of Treatment X X X X X X
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20 CORPORATE LOTIS-7 Phase 1b Trial Path Forward Fully enroll 20 patients per dosing arm in 1H25, potentially expand in recommended dose Complete and present mature data package with more patients and longer duration in 1H25 Plan to engage regulatory authorities on the path forward in late 2025 or early 2026 with more mature data
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21 CORPORATE Agenda ❑ ZYNLONTA Strategy and LOTIS-7 Overview ❑ ZYNLONTA LOTIS-7 Trial Results ❑ ZYNLONTA Growth Potential
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22 → Current indication is commercially profitable → More advanced, derisked expansion indications with LOTIS-5 and indolent lymphomas have the potential to bring company to profitability → LOTIS-7 has the potential to establish ZYNLONTA as a backbone therapy in DLBCL $80 M + U.S. peak revenue ZYNLONTA LOTIS-5 / FL & MZL LOTIS-7 $300 M + U.S. peak revenue $500 M + U.S. peak revenue Commercial Profitability Establish DLBCL presence Potential for ZYNLONTA to Deliver $500M+ Peak Revenue
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Thank You