4Q 2023 Earnings Call
March 13, 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 the beginning of Q4 2025, 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 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.
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Agenda
01
02
03
04
05
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Ameet Mallik |
Introduction |
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Chief Executive Officer |
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Kristen Harrington-Smith |
Commercial Highlights |
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Chief Commercial Officer |
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Mohamed Zaki |
Clinical Highlights |
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Chief Medical Officer |
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Patrick van Berkel |
Research Highlights |
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Chief Scientific Officer |
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Pepe Carmona |
Financial Update |
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Chief Financial Officer |
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3
2023: Positioning the Company for Success
Upgraded
Organization
- Management team with extensive commercial, development, and corporate expertise
- Board members with biotech and large pharma leadership experience; larger number of independents
Enhanced ZYNLONTA
Commercialization
- Established new go-to-market model with upgraded talent
- Refined brand positioning and enhanced data generation
Prioritized
Portfolio
- Hematology: ZYNLONTA Life Cycle Management, ADCT-602(CD-22)
- Solid tumors: ADCT-601 (AXL), portfolio of early-stage ADCs based on novel platform
Validated
Research Platform
- Advancing a range of payloads, linkers, and conjugation technologies against multiple targets
- Expanded internal capabilities to enable partnerships for early-stage assets
Realized Cost
Efficiencies
- Right-sizedorganizational structure; trimmed consulting and contractors
- Reduced 3rd party spending, optimized operating structure, and improved return on investments
4
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 additional indications (FL, MZL)
OTHER ASSETS
- ADCT-602(CD22) in Phase 1 in ALL
Solid Tumor Portfolio long Term
KEY ASSETS
- ADCT-601(AXL) in Phase 1 in sarcoma, pancreatic cancer and NSCLC
- Portfolio of investigational ADCs focused on high-value targets, utilizing novel exatecan-based platform
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.
Advancing ZYNLONTA Development in B-Cell Lymphomas
2023 U.S. Market Value2, 5-year prevalence3
DLBCL
$3.1b2, ~109 K patients
1L (~70%)
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FL |
MZL |
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$2.6b2, ~61 K patients |
$1.4b2, ~38 K patients |
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2L (~24%) |
2L (~27%) |
Proportion ofpatientsbyline- |
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1L (~65%) |
1L (~61%) |
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of |
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3L+ (~11%) |
(~12%) |
-therapy* |
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3L+ |
Current Development Areas
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LOTIS-5 and LOTIS-7 potential to move ZYNLONTA into 2L+ DLBCL |
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‒ LOTIS-5: 20 patient safety run-in data showed ORR of 80%, CR of |
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50% with no new safety signals; may need to enroll additional |
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patients to achieve required number of pre-specified PFS events; |
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accelerating patient enrollment/completion expected in 2024 |
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‒ LOTIS-7:Dose-limiting toxicity period cleared for first two dosing |
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levels of ZYNLONTA (90 µg/kg, 120 µg/kg) in both arms; currently |
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enrolling patients at 150 µg/kg |
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IIT suggests ZYNLONTA regimen could provide benefit in 2L+ high- |
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risk FL (96% ORR, 85% CR, N=27); IIT studying ZYNLONTA in 2L+ |
|
MZL |
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‒ Unmet need is significant in these populations |
DLBCL, FL & MZL account for ~60% of mature B-cell lymphomas1*
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Key: |
Current Approval |
Current Development Areas |
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‒ Plan to assess regulatory path and compendial strategy |
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ZYNLONTA combination with bispecifics (LOTIS-7) is also being |
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studied in r/r FL and r/r MZL |
- 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.
Key Business Updates
ZYNLONTA
(loncastuximab
tesirine-lpyl)
Pipeline
Corporate
- 4Q 2023 net product revenues of $16.6M, a 17% increase compared to 3Q 2023
- Deployment of new commercial model resulted in return to growth in community and academic settings
- FY 2023 net product revenue of $69.1M, declined 8% versus prior year primarily due to higher gross-to-net
-
-
- LOTIS-7(Ph1b ZYNLONTA with bispecifics): Cleared DLT period for first two dosing cohorts in both arms and currently enrolling patients at 150 µg/kg
- LOTIS-5(Ph3 ZYNLONTA with rituximab): Accelerating patient enrollment with completion expected in 2024
- ADCT-601(Ph1 targeting AXL): Early signs of anti-tumor activity in sarcoma; initiated screening in pancreatic cancer
- Advancing early-stage portfolio of solid tumor ADCs (targeting Claudin-6, NaPi2b, PSMA and undisclosed target)
- Balance sheet with $278.6M cash at end of FY 2023
- Operating expenses decreased 21% year-over-year¹ reflecting pipeline prioritization and organizational efficiencies
- Cash runway expected to extend into 4Q 2025
-
7 DLT: Dose-Limiting Toxicity; (1) on a non-GAAP basis or 29% on a GAAP measure including stock-based compensation
ZYNLONTA Net Sales: $16.6M in 4Q 2023
Community
- Majority of the opportunity for ZYNLONTA
- Well-suitedclinical profile: highly effective monotherapy with manageable safety that can be administered in outpatient setting
- Prescribing behavior slow to change due to entrenchment of older and/ or less effective agents
Academic
- ZYNLONTA has an important role in academic setting
- Well-positionedfor patients not suited for bispecifics/ CAR-T or who have progressed on these therapies
-
Strategy to leverage positive experience of thought leaders to help community physicians understand where to use
ZYNLONTA
Improved commercial execution
- Sequential volume growth in both community and academic settings in 4Q 2023, despite intensified competition
- Average vials/day rebounded in Nov/Dec to 1H 2023 levels, partially offset by high single digit % increase in GtN from 1H to 2H
- Confident we have right team and strategy to grow ZYNLONTA in 3L/3L+ DLBCL
- GtN: gross to net; 3L/3L+: third-line and third-line plus; DLBCL: Diffuse Large B-Cell Lymphoma
Significant opportunity for ZYNLONTA combinations in 2L+, despite a highly evolving market
ILLUSTRATIVE
MARKET EVOLUTION
3L+
(~6 K
patients)
|
~40% |
Monjuvi |
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CAR-T |
✓ BsAbs1 |
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+ Len |
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Clinical |
ZYNLONTA |
Polivy + |
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Trials |
BR |
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~60% |
Monjuvi + |
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ZYNLONTA |
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Len |
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R-Based |
Polivy + BR |
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Chemo |
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- 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
~35%
|
~65% |
- Need for novel combinations in the 2L and 3L+ in community centers and 3L+ in academic settings with better efficacy and tolerability
2L
CAR-T
Salvage
ZYNLONTA OPPORTUNITY
(~11 K
patients)
+/- ASCT
Clinical
Trials
|
Pola-BR |
R-Based |
Monjuvi + |
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Chemo |
Len |
|
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ZYNLONTA + rituximab has the potential to: |
|
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LOTIS-5 Provide competitive efficacy with a familiar safety profile |
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(Ph3) |
Be a SoC in the 2L+ setting in community centers and 3L+ in |
1L
~30%
R-CHOP
~70%
✓ Polivy + R-
|
academic settings |
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ZYNLONTA + bispecifics combinations may: |
(~30 K
patients)
- Polivy + R-CHP
CHP
R-CHOP
|
LOTIS-7 |
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Improve efficacy over BsAbs and other combinations in 2L+ |
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(Ph1b) |
academic settings |
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Improve CRS rates and enable broader accessibility to |
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community centers in 2L+ |
9
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Academic |
Community |
1. Epcoritamab or Glofitamab. Source: Putnam Associates Primary Research.
SoC: standard of care, BsAbs: bispecific antibodies, CRS: cytokine release syndrome
|
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
- Following observation of higher-than-expected censoring by the clinical team and confirmed with the IDMC, may need to enroll additional patients, beyond the originally planned 350 patients, to achieve the required number of pre-specified progression free survival events
- 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
10 IDMC: Independent Data Monitoring Committee, OS: Overall Survival, ORR: Overall Response Rate, CRR: Complete Response Rate, DoR: Duration of Response
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ADC Therapeutics SA published this content on 13 March 2024 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 13 March 2024 12:39:38 UTC.