AstraZeneca's In-House ADC Pipeline Shows Promise at ESMO

AstraZeneca has unveiled promising data for its in-house antibody-drug conjugate (ADC) pipeline at the European Society for Medical Oncology (ESMO) conference in Berlin, reinforcing the company's commitment to developing next-generation cancer therapies. The pharmaceutical giant's presentation focused on AZD5335, a folate receptor α (FRα)-targeted ADC, demonstrating encouraging efficacy in patients with platinum-resistant ovarian cancer.

AZD5335 Shows Promising Results in Phase 1/2a Study

The phase 1/2a study of AZD5335 involved 189 patients with platinum-resistant ovarian cancer. Key findings from the trial include:

• Efficacy demonstrated across the 1.6 mg/kg to 2.4 mg/kg dose range
• 56.2% of patients in these cohorts showed no cancer progression at a median follow-up of 7.8 months
• Overall response rates of 56%, 56.1%, and 49.2% for the 1.6 mg/kg, 2 mg/kg, and 2.4 mg/kg cohorts, respectively

Matt Hellmann, Vice President of Early Oncology Development at AstraZeneca, stated that the response rate "looks great" and "validates the platform." He emphasized the importance of the company's stable linker payload technology, which is central to building their future ADC portfolio.

Safety Profile and Tolerability

The study also provided insights into AZD5335's safety profile:

• Neutropenia was the most common treatment-related adverse event
• Grade 3 or above neutropenia affected 45.9% of patients in the 2.4 mg/kg dose cohort
• Lower dose cohorts (1.6 mg/kg and 2 mg/kg) showed an absence of significant toxicities
• No unexpected side effects were observed, with toxicities attributable to the payload

Hellmann noted that the safety profile across the range of doses was "very reassuring" and highlighted the absence of unexpected off-target toxicity.

AstraZeneca's Strategic Focus on In-House ADC Development

AstraZeneca's presentation at ESMO underscores the company's strategic shift towards developing its internal ADC pipeline. This move follows the success of Enhertu and Datroway, both products of a collaboration with Daiichi Sankyo. Key aspects of AstraZeneca's ADC strategy include:

• Investment in proprietary linker and topoisomerase I payload technologies
• Development of seven in-house ADCs targeting solid tumors and hematological malignancies
• Focus on building a platform and surface marker library for versatile ADC development

Hellmann emphasized AstraZeneca's unique position in the ADC space, stating, "We're one of the very few that have invested in building [a] platform and the surface marker library, so that we can put the right targets with the right warheads in a multiplicity of ways."

As the ADC market becomes increasingly competitive, AstraZeneca's in-house approach aims to maintain its strong position in the field. The company's strategy contrasts with competitors who have entered the ADC space through mergers, acquisitions, or licensing deals for specific assets.