On May 6, 2024 ADC Therapeutics SA (NYSE: ADCT) reported financial results for the first quarter ended March 31, 2024, and provided business updates (Press release, ADC Therapeutics, MAY 6, 2024, View Source [SID1234642661]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"During the first quarter of 2024, we were pleased to see continued progress from our corporate and capital allocation strategy focused primarily on hematology with ZYNLONTA while advancing our emerging solid tumor pipeline," said Ameet Mallik, Chief Executive Officer of ADC Therapeutics. "In hematology, we delivered sequential ZYNLONTA revenue growth. We were pleased to announce that our LOTIS-7 study of ZYNLONTA in combination with bispecifics has successfully cleared the final dosing cohort and enrollment in Part 2 dose expansion has been initiated. Additionally, we were encouraged by the initial IIT Phase 2 data with ZYNLONTA in MZL which supports potential expansion in MZL and contributes to the overall ZYNLONTA growth strategy in NHL. With multiple potential value-generating catalysts ahead this year including expected completion of enrollment in LOTIS-5, expansion of LOTIS-7 and initial read of ADCT-601 in AXL, I am excited about our prospects for continued progress in 2024."
Recent Highlights and Developments
ZYNLONTA (loncastuximab tesirine-lpyl)
•ZYNLONTA generated product net sales of $17.8 million in the first quarter of 2024, representing a 7% increase over the fourth quarter of 2023 and a 6% decrease over the first quarter of 2023. Sequential quarter-over-quarter growth in the first quarter of 2024 continued, with sales volume increasing in both community and academic settings. The year-over-year net sales decline reflected higher gross-to-net deductions and lower volume, partially offset by a higher price.
Hematology Pipeline
•LOTIS-5: The Phase 3 confirmatory trial for ZYNLONTA in combination with rituximab in patients with 2L+ diffuse large B-cell lymphoma (DLBCL) continues to see accelerated enrollment. The Company expects to complete enrollment of this trial in 2024.
•LOTIS-7: On April 4, 2024, The Company announced the completion of dose escalation in LOTIS-7, a Phase 1b open-label clinical trial evaluating ZYNLONTA in combination with bispecific antibodies glofitamab or mosunetuzumab in heavily pre-treated patients with relapsed/refractory B-cell non-Hodgkin lymphoma (r/r B-NHL). In the dose escalation portion (Part 1) of LOTIS-7, no dose-limiting toxicities (DLTs), no or low-grade cytokine release syndrome (CRS) and no immune effector cell-associated neurotoxicity syndrome (ICANS) were observed across all patients when ZYNLONTA was administered in combination with glofitamab or mosunetuzumab. Additionally, after the first investigator assessment, evidence of anti-tumor activity (complete response or partial response) was observed among the majority of patients, with mixed histologies including r/r DLBCL, follicular lymphoma (FL) and marginal zone lymphoma (MZL). In addition, as of April 19, 2024, initial safety findings showed that the majority of CRS events seen were grade 1 (6 out of 18 patients) or grade 2 (2 of 18 patients, 11%), with no CRS greater than grade 2 observed in either combination arm. Furthermore, all grade 2 events responded to Tocilizumab/corticosteroids with no requirement for pressors or ICU management. Based on the data from Part 1, all three dose levels (90, 120 and 150 µg/kg) have now been cleared and enrollment in Part 2 dose expansion has been initiated with ZYNLONTA administered in combination with glofitamab at the 120 µg/kg and 150 µg/kg dose levels in 2L+ DLBCL patients.
•Investigator-Initiated Trial: As announced by the Company today, May 6, 2024, initial data from an investigator-initiated Phase 2 clinical trial evaluating ZYNLONTA for the treatment of relapsed/refractory (r/r) MZL were presented at the Lymphoma Research Foundation’s 2024 Marginal Zone Lymphoma Scientific Workshop by the trial’s lead investigator. The 50-patient single-arm, open-label Phase 2 multicenter study is currently being conducted at the Sylvester Comprehensive Cancer Center at University of Miami and City of Hope, and led by Izidore Lossos, MD, Professor, Director, Lymphoma Program at the Sylvester Comprehensive Cancer Center, University of Miami. This study is evaluating the safety and efficacy of ZYNLONTA in patients with r/r MZL previously treated with ≥1 line of systemic therapy (ClincalTrials.gov identifier: NCT05296070). As of the data cutoff date of March 30, 2024, 15 patients were evaluable. Of these 15 patients evaluated, 13 achieved a complete response (CR) and one patient achieved a partial response (PR). In this study, ZYNLONTA was generally well tolerated and the safety profile was consistent with the known profile, with two patient discontinuations. All patients who achieved responses had maintained them at the time of the data cutoff with the longest responder reaching approximately 20 months.
Solid Tumor Pipeline
•ADCT-601 (targeting AXL): The Phase 1b trial studying ADCT-601 targeting AXL continues enrolling patients in the pancreatic cancer monotherapy arm, optimizing dose and schedule. The ongoing dose-optimization/expansion phase is comprised of a monotherapy arm including patients with sarcoma, pancreatic cancer and AXL-expressing non-small cell lung cancer (NSCLC) and a combination arm with gemcitabine in patients with sarcoma and pancreatic cancer.
•Early-stage pipeline: On April 9, 2024, the Company hosted a virtual Research Investor Event during which details were shared on strategy and recent business updates as well as the Company’s novel exatecan-based ADC platform. The Company provided details on its four lead candidates – targeting Claudin-6, NaPi2b, PSMA and ASCT2 – which have a differentiated profile based on a novel, proprietary linker approach to tracelessly release exatecan and a high therapeutic index. The Company’s NaPi2b and Claudin-6 targeting ADCs are in IND-enabling studies and PSMA and ASCT2 targeting ADCs are in drug candidate selection stage, expected to complete this year. Preclinical data on the Claudin-6 and NaPi2b programs were shared in presentations at the AACR (Free AACR Whitepaper) Annual Meeting 2024 which demonstrated that each was well tolerated with potent and specific in vitro and in vivo anti-tumor activity.
Upcoming Expected Milestones
ZYNLONTA
•Achieve commercial brand profitability in 2024
•LOTIS-5: Complete enrollment in 2H 2024
•LOTIS-7: Part 2 enrollment complete with initial efficacy/safety update in 2H 2024; full/mature data in 1H 2025
•Investigator-initiated trial in r/r FL: The study is being expanded to 100 patients in a multicenter clinical trial. Updates are anticipated at medical meetings in 2024/2025.
•Investigator-initiated trial in r/r MZL: The study is designed to enroll 50 patients in a multicenter clinical trial. Further updates are anticipated at medical meetings in 2024/2025.
Pipeline
ADCT-601 (targeting AXL)
•Additional data updates from the Phase 1 study in patients with sarcoma, pancreatic cancer and NSCLC in 2H 2024
ADCT-602 (targeting CD22)
•Additional data from the Phase 1 study in 2H 2024
Preclinical
Advancing a broad portfolio of investigational ADCs for solid tumor indications
First Quarter 2024 Financial Results
Cash and Cash Equivalents
Cash and cash equivalents were $234.3 million as of March 31, 2024, compared to $278.6 million as of December 31, 2023. The Company currently expects its cash runway to extend into the fourth quarter of 2025.
Product Revenues
Net product revenues were $17.8 million for the first quarter 2024, compared to $19.0 million for the first quarter 2023. Net product revenues are for U.S. sales of ZYNLONTA. The decrease was primarily due to higher gross-to-net deductions and lower volume, partially offset by a higher price.
Research and Development (R&D) Expenses
R&D expenses were $25.7 million for the first quarter 2024, compared to $38.4 million for the first quarter 2023. R&D expenses decreased due to less investment in camidanlumab tesirine (Cami), as well as productivity initiatives and focused investment toward prioritized development programs. The decrease in R&D expenses related to Cami was primarily due to our evaluation of FDA feedback and decision to stop the program.
R&D expenses for the first quarter 2024 also decreased due to lower share-based compensation expense resulting from fluctuations in the share price and award forfeitures in connection with terminations.
Selling and Marketing (S&M) Expenses
S&M expenses were $11.4 million for the first quarter 2024, compared to $15.4 million for the first quarter 2023. The decrease in S&M expenses was primarily due to lower spend on marketing and advertising, lower wages and benefits, as well as lower share-based compensation expense resulting from fluctuations in the share price and award forfeitures in connection with terminations.
General & Administrative (G&A) Expenses
G&A expenses were $12.0 million for the first quarter 2024, compared to $15.5 million for the first quarter 2023. The decrease in G&A expenses was primarily due to lower share-based compensation expense resulting from fluctuations in the share price and award forfeitures in connection with terminations, lower wages and benefits and insurance costs, partially offset by higher professional fees including audit and legal fees.
Net Loss and Adjusted Net Loss
Net loss was $46.6 million, or a net loss of $0.56 per basic and diluted share, for the first quarter of 2024 and a net loss of $59.4 million, or a net loss of $0.73 per basic and diluted share for the first quarter of 2023. The decrease in net loss is primarily due to lower operating expenses, partially offset by changes in the fair value of our Deerfield warrant obligation and higher accretion of our deferred royalty obligation.
Adjusted net loss, which is a non-GAAP financial measure, was $31.1 million, or an adjusted net loss of $0.38 per basic and diluted share for the first quarter 2024 and $41.8 million, or an adjusted net loss of $0.52 per basic and diluted share for the first quarter 2023. The decrease in adjusted net loss for the quarter primarily reflects our lower operating expenses.
Conference Call Details
ADC Therapeutics management will host a conference call and live audio webcast to discuss first quarter 2024 financial results and provide a company update today at 8:30 a.m. Eastern Time. To access the conference call, please register here. Registrants will receive the dial-in number and unique PIN. It is recommended that you join 10 minutes before the event, though you may pre-register at any time. A live webcast of the call will be available under "Events & Presentations" in the Investors section of the ADC Therapeutics website at ir.adctherapeutics.com. The archived webcast will be available for 30 days following the call.
About ZYNLONTA (loncastuximab tesirine-lpyl)
ZYNLONTA is a CD19-directed antibody drug conjugate (ADC). Once bound to a CD19-expressing cell, ZYNLONTA is internalized by the cell, where enzymes release a pyrrolobenzodiazepine (PBD) payload. The potent payload binds to DNA minor groove with little distortion, remaining less visible to DNA repair mechanisms. This ultimately results in cell cycle arrest and tumor cell death.
The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have approved ZYNLONTA (loncastuximab tesirine-lpyl) for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), DLBCL arising from low-grade lymphoma and also high-grade B-cell lymphoma. The trial included a broad spectrum of heavily pre-treated patients (median three prior lines of therapy) with difficult-to-treat disease, including patients who did not respond to first-line therapy, patients refractory to all prior lines of therapy, patients with double/triple hit genetics and patients who had stem cell transplant and CAR-T therapy prior to their treatment with ZYNLONTA. This indication is approved by the FDA under accelerated approval and in the European Union under conditional approval based on overall response rate and continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Please see full prescribing information including important safety information about ZYNLONTA at www.ZYNLONTA.com.
ZYNLONTA is also being evaluated as a therapeutic option in combination studies in other B-cell malignancies and earlier lines of therapy.