Emerging ADC Innovations Spark a ‘Renaissance’ in the Thriving Oncology Drug Sector
Antibody-drug conjugates (ADCs) are experiencing a surge in interest driven by recent innovations in payload and linker technologies. The global ADC market, valued at just over billion in 2024, is expected to expand to billion by 2029.
ADCs merge the precision of monoclonal antibodies with the efficacy of cytotoxic agents, targeting and eliminating cancer cells, thereby enhancing the effectiveness of existing treatments like chemotherapy. As one of the most promising areas in oncology, next-generation ADCs aim to address challenges related to toxicity and payload delivery, potentially allowing treatment for evasive solid tumors.
In a discussion published in BioSpace, Paul Moore, Chief Scientific Officer at Zymeworks, expressed that ADCs have now reached their “golden age”, as companies diligently work to overcome inherent technological limitations.
Zai Lab Competes in Lung Cancer Space
Among these companies, Zai Lab has unveiled a cutting-edge linker-payload system via MediLink Therapeutics’ proprietary TMALIN, which reduces off-target toxicity by utilizing the tumor microenvironment.
“The previous generation of ADCs lacked control over payloads and release mechanisms,” stated Rafael Amado, Zai Lab’s president. “Now, we can control drug-to-antibody ratios, strategically place drugs within antibodies, and optimize release, minimizing toxic effects.” He emphasized that advancements in ADCs are resulting from an expanded therapeutic window.
Zai Lab’s investigational next-gen ADC, ZL-1310, features a humanized anti-DLL3 antibody attached to a camptothecin derivative. DLL3 is a Notch ligand inhibitor prevalent in small cell lung cancer (SCLC) and neuroendocrine tumors.
During the ENA Symposium, Zai Lab presented Phase I data on ZL-1310, indicating robust anti-tumor activity and reduced toxicity in relapsed/refractory SCLC cases.
The response rate in extensive-stage SCLC patients for ZL-1310 was 74%, showcasing efficacy across all dose levels, while the ADC demonstrated a favorable safety profile with mostly Grade 1 or 2 adverse events.
In an analyst note, Jefferies’ Michael Yee highlighted the study results as “very promising” and noted ZL-1310’s strong efficacy and safety compared to Amgen’s tarlatamab, which achieved FDA accelerated approval.
“It’s early, but we’ll see how these numbers evolve,” Amado noted.
Total Optimization in Development
Sutro Biopharma, known for the ADC luvelta targeting folate receptor-α in ovarian cancer, is also innovating next-gen ADCs to enhance efficacy and reduce toxicity. The company’s pipeline includes dual-payload and immunostimulatory ADCs.
Sutro’s CEO, Bill Newell, pointed out that only around 1% of the ADC dose reaches the tumor, allowing the remainder to cause unwanted side effects. The company aims for a higher drug-to-antibody ratio, designed to minimize toxicity.
“The linker technology we utilize is among the most stable, and this enhances the potency of our ADCs,” he commented. Sutro is looking to file an IND for STRO-004, an ADC featuring a DAR of 8, with expectations of an FDA submission in late 2025.
Newell believes that the XpressCF platform enables the precise design of ADCs with unique features, setting Sutro apart in the field.
Focus on Potent Payloads
ADC Therapeutics is developing next-gen ADCs targeting hematologic cancers and solid tumors. The company’s PBD dimer technology facilitates the creation of potent DNA cross-linking agents.
Its approved product, Zynlonta, recognized as a CD19-directed ADC, received accelerated FDA approval for adults with refractory large B-cell lymphoma.
“PBD payloads are significantly more potent than typical ADC payloads,” stated CEO Ameet Mallik. “However, strong linker systems are essential for effective delivery.”
Mallik also acknowledged the potential for ADCs in autoimmune diseases, noting the differences in desired effects compared to oncology applications.
In summary, the landscape for ADCs is evolving rapidly, with multiple companies delivering innovative solutions that hold promise for enhanced cancer therapies and beyond.