ADC Therapeutics Weighs New Path After FDA LOTIS-5 Concerns

The Tip Desk · August 13, 2026 · 3 min read

Net product revenue was $18.6 million in the second quarter as the company cut about 17% of its workforce and estimated $10 million in annualized savings.

ADC Therapeutics SA (ADCT) said the U.S. Food and Drug Administration raised substantial concerns about the benefit-risk of its LOTIS-5 confirmatory trial of ZYNLONTA plus rituximab in second-line-plus diffuse large B-cell lymphoma, and that it is now assessing the best regulatory path after a June pre-supplemental Biologics License Application meeting.

The antibody-drug conjugate company had met LOTIS-5’s primary endpoint of progression-free survival and had planned an sBLA. The FDA flagged an imbalance in Grade 5 events against a marginal treatment benefit. ZYNLONTA remains available under accelerated approval as a monotherapy in third-line-plus DLBCL, and ADC Therapeutics said it plans to continue commercializing in that setting.

Commercial sales in the approved monotherapy indication stayed broadly in line with recent quarters. Net product revenue was $18.6 million in the second quarter, down from $20.0 million in the first quarter. The year-over-year increase versus $18.1 million a year earlier was driven by higher price. License revenue and royalties were $0.6 million.

The quarter’s other operational turn was a global workforce reduction of about 17%, driven by the expected completion of LOTIS-5 and LOTIS-7 and by operational efficiencies. The company estimated about $10 million of annualized cost savings and said it is resourced to keep its clinical, regulatory, manufacturing, medical affairs and commercial footprint for ZYNLONTA. Severance and related benefit costs were $2.7 million in the second quarter.

Research and development expense fell to $17.4 million from $30.1 million a year earlier, due to lower spending on discontinued programs, completion of IND-enabling work for its PSMA-targeting ADC, and a $1.7 million shift of personnel costs into cost of product sales, inventory capitalization and selling and marketing. Cost of product sales was $2.3 million. Selling and marketing expense was $12.6 million, and general and administrative expense was $9.7 million. Total operating expenses declined 29% to $44.7 million from $63.0 million a year earlier; adjusted total operating expenses fell 22% to $37.2 million, primarily on lower R&D.

Net loss narrowed to $16.6 million, or $0.11 a share, from $56.6 million, or $0.50 a share, a year earlier. Adjusted net loss was $16.3 million, or $0.11 a share. The lower loss was primarily due to lower operating expenses and, on a per-share basis, a higher number of weighted average shares outstanding. Cash and cash equivalents were $219.1 million as of June 30, 2026, down from $231.0 million at March 31, 2026. The company still cited an expected cash runway at least into 2028.

LOTIS-7 enrollment completed at 100 patients on the 150 µg/kg starting dose of ZYNLONTA plus glofitamab. The data support the company’s belief that the combination shows the most compelling combination data generated to date in second-line-plus DLBCL, with a safety profile generally consistent with prior disclosures, and the company is assessing a Phase 3 trial. It plans to submit for Breakthrough Therapy designation this year. Abstracts for LOTIS-5, LOTIS-7 and a marginal zone lymphoma investigator-initiated trial have been submitted to the 68th American Society of Hematology meeting.

Chief Executive Officer Ameet Mallik said the company will work closely with the FDA to determine how to obtain full approval and advance ZYNLONTA combinations into earlier lines of DLBCL. Chief Medical Officer Mohamed Zaki said the company anticipates growth starting in 2027 and expects to submit LOTIS-7 and MZL data to the FDA for Breakthrough Designation.