1Q 2024 Earnings Call
May 6, 2024
Agenda
01
02
Q&A
Ameet Mallik |
Business Update |
Chief Executive Officer |
|
Pepe Carmona |
Financial Update |
Chief Financial Officer |
|
Kristen Harrington-Smith |
Mohamed Zaki |
Chief Commercial Officer |
Chief Medical Officer |
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 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", "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: statements regarding the underwritten offering; the expected cash into mid-2026; ; the success of the Company's corporate strategy ;the timing and future results from the University of Miami's investigator-initiated trials in FL and MZL, future FDA approval and/or NCCN compendia inclusion and the market size and potential opportunity; the effectiveness of the new commercial go-to-market strategy, competition from new technologies, and the Company's ability to grow ZYNLONTA® revenue in the United States; Swedish Orphan Biovitrum AB's (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' clinical trials including LOTIS 5 and 7, ADCT 601 and 602 as well as the Company's early-stage pipeline research projects, actions by the FDA or foreign regulatory authorities with respect to the Company's products or product candidates; projected revenue and expenses; the Company's indebtedness, including Healthcare Royalty Management and Oaktree and Blue Owl 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 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 reports and filings with the 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. The Company undertakes no obligation to revise or update these forward-looking statements to reflect events or circumstances after the date of this press release, except as required by law.
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.
This presentation also includes non-GAAP financial measures. These non-GAAP measures have limitations as financial measures and should be considered in addition to, and not in isolation or as a substitute for, the information prepared in accordance with GAAP. You should refer to the information contained in the company's fourth quarter earnings release for definitional information and reconciliations of historical non-GAAP measures to the comparable GAAP financial measures.
3
Key Business Updates
Commercial Performance
Pipeline
Progress
- ZYNLONTA® 1Q 2024 net product sales of $17.8M, a 7% increase compared to 4Q 2023
- Continued volume growth in the academic and community settings
- LOTIS-7cleared dose escalation; dose expansion underway with glofit combo in 2L+ DLBCL
- Initial data for ZYNLONTA in MZL IIT in 15 patients showed 13 achieved a CR and 1 a PR
- ADCT-601targeting AXL enrolling in sarcoma and pancreatic; optimizing dose and schedule
- Novel exatecan-based solid tumor platform highlighted at Research Investor Event
§ Operating expenses decreased 29% (or 16%¹ on an as adjusted basis) year-over-year
Corporate |
§ Balance sheet with $234.3M cash at end of 1Q 2024 |
Update |
|
§ Priced a $105.0M underwritten offering; cash runway expected to extend into mid 2026 |
DLT: Dose-Limiting Toxicity; ICANS: immune effector cell-associated neurotoxicity syndrome; CRS: cytokine release syndrome; MZL: marginal zone lymphoma; IIT: investigator-initiated trial; ORR: overall response rate; CR: complete
response; PR: partial response; (1) on a non-GAAP basis or 29% on a GAAP measure including stock-based compensation |
4 |
Unlocking Potential Value of Robust ADC Portfolio
Hematology Portfolio
Short-Mid Term
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
Solid Tumor Portfolio
Term
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, ASCT2
- Continuing research with a range of payloads, linkers, and conjugation technologies against undisclosed targets
DLBCL: Diffuse Large B-CellLymphoma; FL: Follicular Lymphoma; MZL: Marginal Zone Lymphoma; NSCLC: Non-Small Cell Lung Cancer; ALL: Acute Lymphoblastic Leukemia. |
5 |
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. |
6 |
Clarivate DRG (2022) and Global Data (2017); 3. Cerner Enviza CancerMPact (2023). |
ZYNLONTA R/R MZL Opportunity Overview
Phase 2 University of Miami IIT Initial Data
Estimated 3 - 4 K 2L+ MZL patients are drug-treatedin the US1; despite patients achieving durable responses, high unmet medical need remains with <30% CR for 2L+ NCCN preferred treatments2
2 FDA approved regimens (n = 63 - 68; CR 26 - 29%) & several others preferred for 2L+ in NCCN guidelines (n = 43 -
46; CR 13 - 17%)*
Initial data^ from ZYNLONTA r/r MZL University of Miami Ph2 IIT in 15 patients (n total = 50) showed 13 achieved a complete response and 1 achieved a partial response; ZYNLONTA was generally well-tolerated,and safety was consistent with the known profile
2 sites currently enrolling, expanding to 5 sites to accelerate trial enrollment; ADCT plans to potentially pursue regulatory pathway and compendia in parallel as soon as sufficient data is available
Total addressable 2L+ MZL patient population has a potential peak market value of approximately $500 M3; Potential expansion in MZL contributes to the overall ZYNLONTA growth strategy in NHL
*Data as of April 29, 2024; does not include R-CHOP,R-CVP, or B-R which are included in 2L+ NCCN preferred guidelines based on 1L systemic therapy data only; ^As of the data cutoff date of March 30, 2024. Source: 1. Clarivate DRG (2022), Global Data (2017), |
|
Cerner Enviza CancerMPact (2023); 2. MAGNOLIA: ph2, single arm in r/r MZL, AUGMENT: ph3, randomized of R2 vs. R in r/r iNHL, GADOLIN: ph3 randomized of benda vs. benda + obin in r/r iNHL, ACE-LY-003: ph2, part 2 (r/r MZL cohort) of 3 part ph1b/2 study |
|
of acalabrutinib alone or in combination in B-cell NHL; 3. Assumes total addressable population and average net price for ZYNLONTA in 2030 with a CAGR of ~2% and ~3% respectively, and average cycles expected in MZL. |
7 |
Response Rates in Relapsed / Refractory MZL for Current NCCN Preferred Regimens with 2L+ Data
NCCN Preferred^, FDA Approved Regimens
NCCN Preferred Regimens^
CR PR
68% ORR
42%
26%
Zanubrutinib2
n = 68
65% ORR
36%
29%
R24
n = 63
CR PR
79% ORR
62%
17%
Benda* + Obin1
n = 46
53% ORR
40%
13%
Acalabrutinib3
n = 43
Data as of April 29, 2024; Note: n = total # of MZL patients in the study; ^ Data does not include R-CHOP,R-CVP, or B-R data which are included in 2L+ NCCN preferred guidelines based on 1L systemic therapy data only; |
|
*Bendamustine mono-therapy has broad FDA approval in indolent B-cellnon-Hodgkin lymphoma after R-containing regimens, however, is not specific to MZL; bendamustine combinations are not FDA approved for MZL and are |
|
guidelines only. Source: 1. GADOLIN study (randomized ph3 of B + O vs. B; total n = 396, total MZL n= 46, B+O MZL n = 27); 2. MAGNOLIA Trial (single arm, multicenter ph 2; n = 68); 3. ACE-LY-003 study (part 2 of multicenter, ph |
8 |
1/2b; n = 43); 4. AUGMENT study (randomized ph3 of R2 vs. R; total n = 358, total MZL n = 63, R2 MZL n = 31, R mono MZL n = 32). |
|
- Phase 2, Open-label, IIT Evaluating Safety and Efficacy of Loncastuximab in R/R MZL
Clinical Design
R/R MZL Previously Treated with ≥ 1 Line of Systemic
Therapy
CT / MRI or FDG- PET / CT |
Bone Marrow |
|
Loncastuximab 150 μg / kg (Day 1, +/- 3) |
Cycles 1 - 2 |
Study Overview
- A multi-institutional study of 50 patients with r/r MZL after previous systemic treatment (clinicaltrials.gov ID: NCT05296070)
- 2 sites currently enrolling, expanding to 5 sites
- Futility analysis after 20 patients
CT / MRI or FDG- PET / CT based on PET Avidity at screening
Study Rationale
§ The null hypothesis is H0: P≤P0, and the alternative hypothesis is
Loncastuximab 75 μg / kg (Day 1 +/-3 q 21 days) |
Ha: P≥P1 |
|||
Cycles 3 - 6 |
§ |
The best reported CR rate for relapsed MZL using single agent at |
||
30 Days |
study initiation was reported with umbralisib - 16% in 69 patients |
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CT / MRI or FDG- PET / CT based on PET Avidity at screening |
treated1 |
|||
Based on this estimate, under the null hypothesis, we assumed |
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CR by Imaging |
§ |
|||
No CR by Imaging |
Confirmation by bone marrow |
the CR rate (P) to be 16% (P0) |
||
§ |
Expected a 15% increase in the CR rate, resulting in CR rate of 31% |
|||
or greater. Thus, under the alternative hypothesis, the CR rate for |
||||
End of Study / Follow-up |
the proposed treatment is 31% (P1) |
|||
Source: 1. UTX-TGR-205 Study (two single-arm cohorts; total n = 710, total MZL n = 69). |
9 |
Patient Baseline Characteristics from Initial Data
15 evaluable patients out of 20 enrolled patients as of 04/18/2024
Baseline Characteristics |
N |
Number of patients |
15 |
Age, average (range), years |
64 (48 - 80) |
Gender (M:F) |
3:12 |
Ethnicity |
|
White non-Hispanic |
6 |
White Hispanic |
8 |
Black |
1 |
MZL type |
|
EMZL, n (%) |
11 (73%) |
NMZL, n (%) |
3 (20%) |
SMZL, n (%) |
1 (7%) |
ECOG 0 - 1 |
15 |
Stage |
|
I |
2 |
II |
0 |
III |
3 |
IV |
10 |
N of previous line of treatment |
2 (1 - 4)* |
Relapsed/Refractory |
12/3 |
POD24 |
8 |
*Prior lines of treatment included current standard of care including R-based regimens, systemic chemo, BTKis, and CAR-T.
Previous Treatments |
N |
|
Non-systemic |
XRT |
3 |
Splenectomy |
1 |
|
Systemic |
Rituximab |
6 |
R-CHOP |
5 |
|
BR |
3 |
|
R2 |
1 |
|
Ibrutinib |
1 |
|
Zanubrutinib |
1 |
|
Zevalin |
1 |
|
R-MVP |
1 |
|
RICE |
1 |
|
R-GemOx |
1 |
|
CAR-T |
1 |
|
10
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Disclaimer
ADC Therapeutics SA published this content on 06 May 2024 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 06 May 2024 12:38:40 UTC.