Tubulis Begins Phase I/IIa Trial of ADC TUB-040 in Ovarian Cancer and Lung Adenocarcinoma

Tubulis, a biotechnology company based in Munich, has announced the treatment of the first patient in its initial Phase I/IIa clinical trial, named NAPISTAR 1-01 (NCT06303505). This trial is examining the effectiveness of TUB-040, a next-generation antibody-drug conjugate (ADC), in patients suffering from platinum-resistant high-grade ovarian cancer (PROC) or relapsed/refractory adenocarcinoma non-small cell lung cancer (NSCLC). These patients have exhausted all other available treatment options. TUB-040 specifically targets NaPi2b, an antigen significantly overexpressed in both types of cancer. This candidate is the first from Tubulis' expanding pipeline to reach clinical trials and showcases the company's proprietary technology platforms designed to produce ADCs with enhanced biophysical properties.

The clinical trial is a multicenter, first-in-human study focusing on dose escalation and optimization. It aims to assess the safety, tolerability, pharmacokinetics, and efficacy of TUB-040 as a standalone treatment. The trial will be conducted in the US, the UK, Spain, Belgium, and Germany. Phase Ia involves dose escalation to identify the maximum tolerated dose or the optimal dose, while Phase IIa will concentrate on dose optimization, safety, and preliminary efficacy. The first patient has already been dosed in the US following approval from the FDA.

Dr. Günter Fingerle-Rowson, the Chief Medical Officer at Tubulis, expressed optimism about TUB-040's potential. He highlighted how ADCs are emerging as a fundamental treatment alternative to traditional chemotherapy for various solid tumors. Based on preclinical data, Dr. Fingerle-Rowson believes that TUB-040 could offer a new, effective treatment option for patients with NSCLC and ovarian cancer. According to him, the innovative P5 technology used in TUB-040 addresses the primary challenges of current ADC treatments, such as off-target toxicity and limited durability. By minimizing non-target toxicity and ensuring a more specific, continued on-tumor delivery of the payload, Tubulis aims to enhance long-term anti-tumor responses and clinical outcomes for patients.

Dominik Schumacher, Tubulis' CEO and Co-founder, emphasized the significance of initiating their first clinical trial. He articulated that this milestone underscores the company's commitment to innovating across all aspects of ADC design for patient benefit. Schumacher stated that the goal is to achieve clinical proof-of-concept for TUB-040 and validate their unique platform approach to ADC development.

TUB-040 comprises a humanized, target-specific, Fc-silenced IgG1 antibody linked with Tubulis' proprietary Tubutecan linker-payload technology. This technology is founded on P5 conjugation chemistry and includes the topoisomerase-1 inhibitor Exatecan. Tubulis presented comprehensive preclinical data at the AACR, demonstrating TUB-040's superior stability and minimal loss of linker-payload conjugation. In various preclinical models, TUB-040 showed significant and prolonged anti-tumor responses, even at lower expression levels of NaPi2b, coupled with excellent safety and tolerability.

The P5 technology, central to TUB-040, enables unprecedented linker stability and biophysical properties through cysteine-selective conjugation. Originating from research by Prof. Christian Hackenberger at the Leibniz-Forschungsinstitut für Molekulare Pharmakologie, this technology utilizes phosphorus chemistry for superior bioconjugation. Preclinical pharmacokinetic analyses have shown that TUB-040 efficiently delivers its payload to the tumor while reducing off-site toxicities. The candidate is currently being investigated in a multicenter Phase I/IIa study to evaluate its safety, tolerability, pharmacokinetics, and efficacy as a monotherapy.

Tubulis continues to advance its suite of proprietary platform technologies, aiming to create uniquely matched ADCs with superior biophysical properties for the treatment of solid tumors. The company is committed to expanding the therapeutic potential of ADCs through continuous innovation, benefiting its pipeline, partners, and patients.