ADC Therapeutics(ADCT)2025-03-27 11:39ZYNLONTA Efficacy and Clinical Trial Results - ZYNLONTA monotherapy achieved 48.3% ORR and 24.8% CR in adult patients with relapsed or refractory large B-cell lymphoma, with a median time to CR of 1.5 months[22] - LOTIS-5 (ZYNLONTA + rituximab) showed 80% ORR and 50% CR in a 20-patient safety run-in, with full enrollment completed in 2024[26][29] - LOTIS-7 (ZYNLONTA + bispecific) demonstrated 94% best ORR and 72% CR rate in initial efficacy data (n=18) with a manageable safety profile (n=29)[26] - ZYNLONTA + rituximab in high-risk r/r FL achieved 97% ORR and 77% CR (n=35)[26] - ZYNLONTA monotherapy in r/r MZL showed 91% ORR and 70% CR (n=23)[26] - LOTIS-7 Phase 1b Trial: Best Overall Response indicates an ORR of 94% (17 out of 18) and a CR rate of 72% (13 out of 18) in the efficacy evaluable population[38] - ZYNLONTA Phase 2 IIT Data shows a 70% CR rate in r/r MZL patients, with 91% ORR (21 out of 23) and 70% CR (16 out of 23)[46] - ZYNLONTA + Rituximab Phase 2 IIT Data shows a 77% CR rate in r/r FL patients, with 91% ORR (21 out of 23) and 70% CR (16 out of 23)[47] - Best ORR of 97.4% (n=38) and CR rate of 76.9% (n=30) in a study evaluating ZYNLONTA, with a 12-month PFS of 94.6% after a median follow-up of 15.6 months[63] ZYNLONTA Safety Profile - LOTIS-7 Phase 1b Trial: Safety Summary shows Grade 3/4 TEAEs in 55.2% of patients (16 out of 29), with neutropenia being the most common at 24.1% (7 out of 29)[36] - LOTIS-7 Phase 1b Trial: CRS/ICANS Profile & Management reports 34.5% of patients (10 out of 29) experienced any grade of Cytokine Release Syndrome (CRS), with no Grade >3 cases[37] - Safety profile of ZYNLONTA consistent with known data, with no Grade 5 TEAEs reported[63] ZYNLONTA Commercial and Financial Performance - ZYNLONTA stabilized sales and achieved commercial brand profitability despite increased competition[15] - Cash runway is expected to extend into mid-2026, supported by disciplined portfolio management and double-digit cost reductions[15] - ZYNLONTA U.S. Peak Revenue Potential is estimated at 200-300M[55][56] - Future Treatment Shares by Line of Therapy indicate that ZYNLONTA + Rituximab could capture 22% of 2L patients and 21% of 3L+ patients, with a median number of cycles increasing from three to five[57] Next-Generation ADC Platform and Pipeline Development - The company is advancing a next-generation ADC platform targeting Claudin-6, PSMA, NaPi2b, and ASCT2 with an exatecan-based payload and novel hydrophilic linker[13] - ADCT advancing a broad portfolio of investigational ADCs targeting Claudin-6, PSMA, NaPi2b, and ASCT2, with IND-enabling studies ongoing[68] - ADCT's proprietary linker technology enables precise site-specific attachment of diverse payloads with tunable DAR[60] - ADCT's exatecan-based ADCs show increased bystander effect, potency, and lower risk of multi-drug resistance compared to DXd[67] - Exatecan-based ADC demonstrated superior therapeutic index and better response compared to DXd-based ADC at equivalent doses[67] Corporate Strategy and Business Development - Corporate strategy includes co-development, royalty, and milestone-based partnerships to maximize deal value and accelerate asset development[69] - ZYNLONTA potential BLA submission to regulatory authorities expected by end of 2025, with topline results anticipated[71] - ADCT plans to pursue business development opportunities to expand the portfolio and fund early-stage pipeline[71] Clinical Trial Expansion and Updates - LOTIS-7 Phase 1b trial of ZYNLONTA in combination with glofitamab began enrollment in July 2023, with dose escalation completed and initial efficacy/safety updates expected[31][32] - University of Miami expanding the trial to 100 high-risk r/r FL patients and opening the study at additional US cancer research centers[63] ZYNLONTA Market Positioning and Indication Expansion - ZYNLONTA is positioned for potential expansion into earlier lines of therapy and new indications, including 2L+ DLBCL and indolent lymphomas (FL and MZL)[11][25]