FDA Grants Fast Track to Tubulis' Antibody-Drug Conjugate TUB-040 for Platinum-resistant Ovarian Cancer

Tubulis has announced that its lead antibody-drug conjugate (ADC), TUB-040, has been granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the treatment of patients with platinum-resistant ovarian cancer. TUB-040 is a cutting-edge NaPi2b-targeting Exatecan ADC, leveraging Tubulis’ innovative P5 technology. This advanced candidate has shown promising biophysical properties and demonstrated effective, lasting responses in various preclinical models, including ovarian cancer.

The designated Fast Track status is a significant milestone, as it facilitates more frequent interactions with the FDA to expedite the development and review process of new therapies aimed at addressing serious conditions and unmet medical needs. Programs with this status may qualify for accelerated approval and priority review if specific criteria are met.

Currently, TUB-040 is under evaluation in a multicenter Phase I/IIa study named NAPISTAR 1-01 (NCT06303505). This trial, conducted across the US, UK, Spain, Belgium, and Germany, aims to assess the safety, tolerability, pharmacokinetics, and efficacy of TUB-040 as a monotherapy. The study is divided into two phases: Phase Ia focuses on dose escalation to determine safety and maximum tolerated or optimized dose, while Phase IIa centers on dose optimization, safety, and preliminary efficacy.

Ovarian cancer (OC) remains the deadliest gynecological cancer among women. Early detection significantly improves survival rates, but many cases are diagnosed at later stages due to non-specific symptoms and lack of effective screening methods. The standard treatment is platinum-based chemotherapy, yet around 20% of patients develop resistance to this therapy at each stage of treatment. Platinum-resistant OC, defined by disease recurrence during or within six months post-platinum-based therapy, is linked to poor outcomes and low response rates to subsequent treatments. Median survival for these patients is approximately 12-16 months, underscoring the urgent need for new therapeutic options.

TUB-040 targets NaPi2b, an antigen highly overexpressed in ovarian cancer and lung adenocarcinoma. It comprises an IgG1 antibody aimed at NaPi2b, connected to the Topoisomerase I inhibitor Exatecan through a cleavable linker system derived from P5 conjugation technology. This technology enables the creation of ADCs with remarkable linker stability and biophysical properties, resulting in a homogeneous drug-to-antibody ratio (DAR) of 8. Originating from the research of Prof. Christian Hackenberger at the Leibniz-Forschungsinstitut für Molekulare Pharmakologie, P5 conjugation employs phosphorus chemistry for superior bioconjugation. Preclinical studies have shown that TUB-040 efficiently delivers its payload to tumors while minimizing off-target toxicities.

Tubulis is at the forefront of developing ADCs with exceptional biophysical properties tailored for solid tumors. Their approach ensures durable delivery and prolonged anti-tumor activity, as evidenced by TUB-040's progress in ovarian and non-small cell lung cancer. Tubulis plans to advance its pipeline with the next candidate, TUB-030, and aims to maintain its leadership by continuing to innovate ADC design, expanding therapeutic potential for its pipeline, partners, and patients.