ADC THERAPEUTICS SA Corporate Presentation
2Q 2024
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 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", "assumes", "will", "should", "would", "expect", "intend", "plan", "anticipate", "believe", "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. Factors that may cause such differences include, but are not limited to: the success of the Company's updated corporate strategy; the expected cash runway into mid-2026, the effectiveness of the 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 reimbursement coverage, and future revenue from the same; approval by the NMPA of the BLA for ZYNLONTA® in China submitted by Overland ADCT BioPharma and 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 future revenue and payments to us from such partnerships; the timing and results of the Company's or its partners' research and development projects or clinical trials including LOTIS 5 and 7, ADCT 601 and 602 as well as IITs in FL and MZL and early research in certain solid tumors with different targets, linkers and payloads; the timing and outcome of regulatory submissions or NCCN compendia inclusion for the Company's products or product candidates; actions by the FDA or foreign regulatory authorities; projected revenue and expenses; the Company's ability to enter into business development or research collaboration transactions; 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 indebtedness 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 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 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 forward-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, conditions, 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.
2
ADC Therapeutics at a Glance
Platform
Pioneering ADC field with robust technology toolbox and specialized end-to-end capabilities
Hematology
Maximizing ZYNLONTA® in 3L+ DLBCL and expanding into earlier lines of
DLBCL and indolent lymphomas; advancing ADCT-602 targeting CD22
Solid Tumors
Advancing ADCT-601 targeting AXL in the clinic and multiple investigational ADCs
Corporate
Cash runway into mid 2026* with multiple catalysts through 1H 2025
*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 . ADC: Antibody Drug Conjugate;
- DLBCL: Diffuse Large B-Cell Lymphoma
Platform and Capabilities for Developing Optimized ADCs
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
- CMC: Chemistry, Manufacturing and Controls; PBD: Pyrrolobenzodiazepines
Clinical
Strong track record including an approved product with robust lifecycle management and multiple clinical assets
Regulatory
Proven capabilities securing FDA and EMA approvals for ZYNLONTA and multiple INDs
Platform
Validated and differentiated ADC platform with multiple payloads and targets
Corporate and Capital Allocation Strategy Based on Twin Pillars of Hematology and Solid Tumors
Hematology Portfolio
Short-Mid Term
ZYNLONTA
- Primary focus for capital allocation
- De-riskedasset with $500M+ peak sales potential
- Investing to optimize commercial execution in 3L+ DLBCL and potential expansion into earlier lines (LOTIS-5: rituximab combination, LOTIS-7: bispecific combinations) and indolent lymphomas (FL and MZL)
OTHER ASSETS
- ADCT-602(CD22) in Phase 1 in ALL
Solid Tumor Portfolio
ADCT-601 (AXL)
- Optimizing dose for expansion as single agent and / or in combination in sarcoma, pancreatic, and NSCLC
Next-generation ADCs
- Differentiated exatecan-based payload with novel hydrophilic linker, targeting Claudin-6, NaPi2b, PSMA, ASCT2
- Advancing one candidate to IND
COLLABORATION STRATEGY
- Partnership/collaboration approach to support progression of broad early-stage portfolio
- Non-dilutivecapital from partners to help fund internal development of select solid tumor programs
- DLBCL: Diffuse Large B-Cell Lymphoma; FL: Follicular Lymphoma; MZL: Marginal Zone Lymphoma; NSCLC: Non-Small Cell Lung Cancer; ALL: Acute Lymphoblastic Leukemia.
Focused Pipeline in Hematology and Solid Tumors
Preclinical | Phase 1a | Phase 1b | Phase 2 | Phase 3 / | Expected Milestones |
Confirmatory |
ZYNLONTA | Targeting CD19 | |
LOTIS-2 in 3L+ DLBCL | |
Hematology | LOTIS-5 with rituximab in 2L+ NTE DLBCL |
U of Miami IIT single agent in r/r MZL | |
LOTIS-7 with glofitamab in r/r NHL1 | |
LOTIS-7 with mosunetuzumab in r/r NHL1 | |
U of Miami IIT with rituximab in r/r FL |
ADCT-602| Targeting CD22
Acute Lymphoblastic Leukemia
Mipasetamab uzoptirine (ADCT-601) | Targeting AXL
Single agent and with gemcitabine in adv. / met. Sarcoma | |
Tumors | Single agent and with gemcitabine and others in adv. / met. Pancreatic |
Single agent and other combinations in adv. / met. NSCLC2 | |
Solid | Next-Gen ADCs | Exatecan Payload with Novel Linker |
NaPi2b | |
Claudin-6 | |
PSMA | |
ASCT2 |
FDA approved (AA) Confirmatory
LOTIS-5: Complete enrollment in 2024
LOTIS-7: Initial dose expansion data with glofitamab in 2H 2024
IITs: Updates at medical meetings in 2024 / 2025
Additional data from Phase 1 study in 2024
Additional data from Phase 1 study in 2024
Candidate selected Candidate selected Candidate selection in 2024 Candidate selection in 2024
6 | Anticipated milestones set forth in this chart are subject to further future adjustment. NTE: Non-TransplantEligible. 1. DLBCL, FL, MZL 2. Non-selected advanced / metastatic NSCLC completed. Moving forward with AXL expressing NSCLC contingent on in-house IHC assay. |
AA: Accelerated Approval. | |
Advancing ZYNLONTA Development in B-Cell Lymphomas
Projected U.S. Market Value2, 2023 5-year prevalence3
DLBCLFL
$3.1b2, ~109 K patients | $2.6b2, ~61 K patients |
1L (~70%) | 1L (~65%) |
2L (~24%)
3L+ (~11%)
MZL^
$1.4b2, ~38 K patients
1L (~61%) | Proportionofpatientsby |
2L (~27%) | line |
(~12%) | -of-therapy* |
3L+ |
Current Development Areas
§ LOTIS-5and LOTIS-7 potential to move ZYNLONTA into 2L+ DLBCL |
‒ LOTIS-5(ZYNLONTA + R): 20 patient safety run-in data showed |
ORR of 80%, CR of 50% with no new safety signals; accelerating |
patient enrollment/completion expected in 2024 |
‒ LOTIS-7(ZYNLONTA + BsAbs): Dose escalation in Phase 1b trial |
completed with no dose-limiting toxicities and early signs of anti- |
tumor activity; Part 2 dose expansion initiated with ZYNLONTA in |
combination with glofitamab at the 120 µg/kg and 150 µg/kg |
dose levels in 2L+ DLBCL |
§ Initial IIT data suggests ZYNLONTA regimen could provide benefit |
in indolent lymphomas: |
‒ FL 2L+ high-risk (ZYNLONTA + R): 96% ORR, 85% CR, N=27 |
DLBCL, FL & MZL account for ~60% of mature B-cell lymphomas1
Key: | Current Approval | Current Development Areas | ||
‒ MZL 2L+ (ZYNLONTA): 13 achieved a complete response and 1 |
achieved a partial response, N = 15 |
*Distribution by line of therapy is based on the incident, drug-treated population; ^Internal analysis of Global Data (2017) and Clarivate DRG (2022). Source: 1. Leukemia & Lymphoma Society website; 2.
- Clarivate DRG (2022) and Global Data (2017); 3. Cerner Enviza CancerMPact (2023).
Significant opportunity for ZYNLONTA combinations in 2L+, despite a highly evolving market
ILLUSTRATIVE
MARKET EVOLUTION
3L+
(~6 K
patients)
~40% | ||
CAR-T | ✓ BsAbs1 | Monjuvi |
+ Len | ||
Clinical | ZYNLONTA | Polivy + |
Trials | BR | |
~60% | |
ZYNLONTA | Monjuvi + |
Len | |
R-Based | Polivy + BR |
Chemo | |
§ Despite recent advancements, a true SoC only exists in 1L and in |
the academic setting in 2L with CAR-T |
§ Aside from CAR-T, the market is evolving towards combinations |
with off-the-shelf agents as a cornerstone |
§ With polatuzumab moving into 1L, retreatment with pola-based |
combos in 2L+ may be less likely |
2L
(~11 K
patients)
~35% | |
CAR-T | Salvage |
+/- ASCT | |
Clinical | |
Trials |
~65% | ||
Pola-BR | R-Based | Monjuvi + |
Chemo | Len | |
§ Need for novel combinations in the 2L+ in community centers |
and 3L+ in academic settings with better efficacy and tolerability |
ZYNLONTA POTENTIAL
ZYNLONTA + rituximab (LOTIS-5,Ph3) has the potential to:
§ | Provide competitive efficacy with a familiar safety profile |
§ | Be a SoC in the 2L+ setting in community centers and 3L+ in |
1L
(~30 K
patients)
~30%
R-CHOP
- Polivy + R-CHP
~70% | |
✓ Polivy + R- | R-CHOP |
CHP |
academic settings |
ZYNLONTA + bispecifics (LOTIS-7,Ph1b) combinations may:
§ | Improve efficacy over BsAbs and other combinations in 2L+ |
academic settings | |
§ | Improve CRS rates and enable broader accessibility to community |
AcademicCommunity
8 | 1. Epcoritamab or Glofitamab. Source: Putnam Associates Primary Research. |
SoC: standard of care, BsAbs: bispecific antibodies, CRS: cytokine release syndrome | |
centers in 2L+ |
Key ✓ Recently approved | Shifting to 1L use | No standard of care |
LOTIS-5: Developing ZYNLONTA to be the Combination Agent of Choice in Earlier Lines of Therapy
LOTIS-5 Overview
- Patient Population: 2L+ DLBCL, ASCT ineligible
- Summary: Ph3 confirmatory trial in combination with rituximab
- Study Design: Randomized, open-label,two-part,two-arm,multi-center clinical trial of ZYNLONTA combined with rituximab compared to immunochemotherapy in patients with relapsed or refractory DLBCL
- Primary and Secondary Endpoints:
- Primary endpoint - to evaluate the efficacy of ZYNLONTA combined with rituximab compared to standard immunochemotherapy, as measured by PFS
- Secondary endpoints include OS; ORR; CRR; DoR; frequency and severity of adverse events; changes from baseline in safety laboratory and clinical variables; concentration and pharmacokinetic parameters of ZYNLONTA; immunogenicity; and changes in patient- reported outcomes
- Initial Data: Updated safety lead-in results at SOHO 2023: ORR of 80%, CR of 50% with no new safety signals
Status and Next Steps
- Enrollment ongoing in randomized portion; > 2/3rd patients enrolled
- Required number of pre-specified progression free survival events unchanged from original study design; total number of patients enrolled dependent on patient censoring rate
- In January 2024, IDMC noted no safety concerns, recommended study to proceed
- Expect full enrollment in 2024
- Depending on events, potential data by end of 2025
Target Positioning
Competitive 2L+ efficacy with favorable safety and convenient dosing schedule, well-suited for use in both academic and community settings
*As of March 13, 2024
- IDMC: Independent Data Monitoring Committee, OS: Overall Survival, ORR: Overall Response Rate, CRR: Complete Response Rate, DoR: Duration of Response
LOTIS-7: Combining ZYNLONTA with Bispecific Antibodies (Glofitamab or Mosunetuzumab)
Screening | Treatment Period |
Period (≤28 d) | (cycles of 21 days) |
RATIONALE
§ | Distinct MOAs and non-overlapping toxicities, except neutropenia |
§ | Most potent off-the-shelf, single agent drugs approved in DLBCL |
Part 1 3+3 Dose escalation (ZYNLONTA 90, 120, and 150 μg/kg)
Part 2 Dose expansion
r/r DLBCL,
FL, MZL
for both arms
May include r/r DLBCL, FL, and MZL
Glofitamab + escalating doses of ZYNLONTA Q3W1 Enrollment began July 2023
Mosunetuzumab + escalating doses of ZYNLONTA
Q3W2 | E | |
EnrollmentArm | began July 2023 | |
F | ||
ZYNLONTA will be given at RD for the specific | ||
Arm |
combinations and subpopulations determined in part 1
STUDY POPULATION
End of Treatment
§ ZYNLONTA use prior to glofitamab may debulk the tumors and reduce |
peripheral B cells, leading to lower CRS rates |
ENDPOINTS
- Primary: Safety and tolerability; MTD and/or RD
- Secondary: Efficacy: ORR, DOR, CRR, PFS, RFS, OS; Pharmacokinetics and Immunogenicity
Part 1 Dose Escalation Completed
§ Dose escalation in Phase 1b trial completed with no dose-limiting toxicities, |
no or low-grade cytokine release syndrome and no immune effector cell- |
associated neurotoxicity syndrome across all patients and early signs of |
- 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
anti-tumor activity |
§ Part 2 dose expansion initiated with ZYNLONTA in combination with |
glofitamab at the 120 µg/kg and 150 µg/kg dose levels in 2L+ DLBCL |
- 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)
- 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
10 and beyond (reduce ZYNLONTA to 75 μg/kg at C3 if starting dose is 120 ug/kg or higher)
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ADC Therapeutics SA published this content on 14 May 2024 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 14 May 2024 17:53:03 UTC.
