ADC Therapeutics: A High-Conviction Biotech Play Amid Key Catalysts in 2025

In the dynamic world of biotech, few companies have navigated the intersection of innovation and execution as deftly as ADC Therapeutics. With its flagship product, ZYNLONTA (loncastuximab tesirine-lpyl), now a cornerstone in the treatment of relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL), the company is poised to capitalize on a series of near-term clinical and regulatory catalysts in 2025. These milestones not only validate its scientific platform but also position ADC as a compelling long-term investment for those willing to bet on transformative oncology therapies.

Clinical Catalysts: ZYNLONTA's 2025 Momentum

ADC's 2025 progress is anchored by the LOTIS-7 trial, a Phase 1b study combining ZYNLONTA with glofitamab (COLUMVI®) in r/r DLBCL. Updated data from 41 patients revealed an 93.3% overall response rate (ORR) and 86.7% complete response (CR) rate, with 25 of 26 CR patients remaining in remission at the data cutoff. Notably, the combination demonstrated rapid responses, with a median time to CR of just 42 days at the 150 µg/kg dose. These results, presented at EHA2025 and ICML, underscore ZYNLONTA's potential to redefine treatment paradigms in aggressive lymphomas.

The LOTIS-5 Phase 3 trial, evaluating ZYNLONTA plus rituximab in r/r DLBCL, remains on track to reach its prespecified progression-free survival (PFS) events by year-end 2025. A successful outcome would pave the way for a supplemental Biologics License Application (sBLA) in H1 2026, potentially expanding ZYNLONTA's label to earlier lines of therapy. This trial's success is critical, as it could differentiate ZYNLONTA from competitors like Gilead's Yescarta by demonstrating superior durability and broader applicability.

Meanwhile, ZYNLONTA's foray into marginal zone lymphoma (MZL) is gaining traction. A Phase 2 investigator-led trial reported 13 of 15 patients achieving complete responses, with all responders maintaining remission. These data, presented at ICML, highlight ZYNLONTA's versatility in addressing rare B-cell malignancies with high unmet need.

Financial Sustainability: Balancing Burn and Revenue

ADC's financials, while still in the red, show signs of stabilization. Q1 2025 results revealed $17.4 million in ZYNLONTA net product revenues, a modest but encouraging figure given the drug's recent U.S. launch. License and royalty revenues surged to $5.6 million, driven by a $5.0 million milestone payment from Health Canada's ZYNLONTA approval.

Research and development (R&D) expenses rose to $28.9 million in Q1 2025, reflecting investments in next-generation ADCs targeting Claudin-6, PSMA, and ASCT2. However, the company's cash runway remains robust, with $194.7 million in cash as of March 2025, sufficient to fund operations into mid-2026. This liquidity, combined with a $301 million market cap and a stock price of $2.68 as of August 2025, suggests ADC is well-positioned to execute its strategic priorities without immediate dilution risks.

Competitive Differentiation: ZYNLONTA's Market Edge

ZYNLONTA's differentiation lies in its CD19-targeted ADC mechanism, which avoids the manufacturing complexities and toxicity profiles of CAR-T therapies. In a head-to-head comparison with CD19 CAR-T, ZYNLONTA demonstrated superior short-term response rates (90% ORR vs. 46% in single-target CAR-T) in r/r DLBCL, albeit with a higher incidence of hematological toxicity. This trade-off is arguably justified in a market where rapid, durable responses are paramount.

The global r/r DLBCL market, valued at $1.61 billion in 2025, is projected to grow at a 4.3% CAGR through 2032, driven by an aging population and rising adoption of advanced therapies. ZYNLONTA's potential expansion into MZL—a niche market with 3,000–4,000 U.S. patients annually—further amplifies its revenue upside.

Risks and Mitigants

ADC's path is not without challenges. The LOTIS-5 trial must deliver statistically significant PFS and OS improvements to justify a broader label. Additionally, the discontinued ADCT-602 trial in B-cell acute lymphoblastic leukemia highlights the risks of overextending its pipeline. However, ADC's focus on ZYNLONTA and its preclinical programs targeting solid tumors (e.g., Claudin-6) provides a buffer against single-product dependency.

Investment Thesis: A High-Conviction Play

For investors with a 3–5 year horizon, ADC Therapeutics offers a compelling risk-reward profile. Key catalysts in 2025—LOTIS-7 data expansion, LOTIS-5 PFS events, and ZYNLONTA's MZL trial updates—are poised to drive valuation re-rating. The company's $194.7 million cash runway and $75.8 million TTM revenue suggest a path to positive cash flow by 2026, assuming successful trial outcomes.

Moreover, ADC's strategic partnerships with Swedish Orphan Biovitrum (Sobi) for European commercialization and Overland ADCT BioPharma for China's BLA submission underscore its global ambitions. These alliances mitigate commercialization risks and open access to high-growth markets.

Conclusion

ADC Therapeutics is a rare biotech play where scientific innovation aligns with near-term commercial potential. ZYNLONTA's clinical performance in 2025 has already positioned it as a best-in-class therapy for r/r DLBCL, while its expansion into MZL and solid tumors hints at a broader platform. For investors willing to navigate the inherent volatility of clinical-stage biotechs, ADC offers a high-conviction opportunity to participate in a transformative oncology story.