FMP-and LMU-spin-off Tubulis presents first clinical data on TUB-040 in platinum-resistant ovarian cancer (PROC) at the ESMO Congress 2025

P5 conjugation technology as a molecular glue to construct antibody-drug-conjugates (ADCs) for clinical Phase I/II a trials against cancer. © Barth van Rossum

 

The clinical data were first presented in a presentation at the European Society for Medical Oncology (ESMO) Congress in Berlin. Principal Investigator Dr. Antonio Gonzalez-Martin, Director Medical Oncology Department and Cancer Center Director at the Clínica Universidad de Navarra, presented the results of the leading antibody-drug conjugate (ADC) TUB-040 in platinum-resistant high-grade serous ovarian cancer (PROC-HGSOC), focusing on doses between 1.67 and 3.3 mg/kg. This is the first time that clinical data has been available to validate Tubulis' proprietary Tubutecan technology and provide proof of concept for the company's most advanced ADC targeting NaPi2b.

Tubulis relies on innovative P5 conjugation technology in its product development, which plays a key role in the manufacture of its ADCs. This linker chemistry was developed in basic research by Prof. Christian Hackenberger, one of the co-founders of Tubulis, and his team at the FMP and further developed by Tubulis for clinical research, enabling stable, targeted drug delivery.

“These positive first-in-human data for TUB-040 mark a milestone for Tubulis, validate our ADC design strategy and offer a potentially new treatment option for patients with platinum-resistant ovarian cancer”, said Dr Dominik Schumacher, Chief Executive Officer and Co-founder of Tubulis. “Supported by our recent financing, we are in a position to rapidly advance TUB-040 towards pivotal trials and expand its clinical development into earlier disease stages and additional tumor types. The data also provides a foundation to unlock the full potential of ADCs using our Tubutecan platform, expanding its impact to benefit a significant patient population."

Tubulis recently completed a Series C financing round of 308 million euros (US$ 361 million) – the largest of its kind for a European biotechnology company in a Series C round and also the largest financing ever for a private ADC (antibody-drug conjugate) company worldwide. The round was led by Venrock Healthcare Capital Partners, with participation from new investors such as Wellington Management and Ascenta Capital, as well as existing investors.

Clinical Highlights:

By 1 September 2025, 67 patients with platinum-resistant ovarian cancer had been treated with TUB-040, 46 of them in dose cohorts ranging from 1.67 to 3.3 mg/kg. The average age was 62 years. The objective response rate (ORR) was 59%, and the confirmed ORR was 50%. Complete remission was documented at 2.5 mg/kg. The disease control rate was 96%, with 81% of patients showing a positive response to the CA-125 tumor marker. Treatment is still ongoing in 80% of patients. Patients who had previously been treated with mirvetuximab soravtansin also responded to TUB-040.

TUB-040 was generally well tolerated, with predominantly mild to moderate side effects. There were no treatment-related deaths in any cohort and no discontinuations of treatment in the relevant dose cohorts. Clinically relevant complications such as bleeding, pneumonitis or nerve damage did not occur, which distinguishes TUB-040 from other similar agents in this class. Its low-grade and manageable toxicity is also noteworthy. Serious side effects (grade 3 or higher) were rare, including neutropenia (22%), anaemia (9%), thrombocytopenia (4%) and nausea (4%). 

"The interim results show a differentiated clinical profile for TUB-040 with anti-tumor activity and a broad therapeutic window, which could provide treating physicians with flexibility in dosing. The data confirm NaPi2b as a valuable ADC target and confirm that our Tubutecan technology can deliver exatecan for effective tumor targeting with reduced systemic toxicity. Our goal now is to further accelerate the clinical development of TUB-040 in order to bring this valuable drug to patients as soon as possible," said Dr Günter Fingerle-Rowson, MD PhD, Chief Medical Officer of Tubulis.

The ongoing NAPISTAR 1-01 study (NCT06303505) is evaluating TUB-040 and aims to assess the safety, tolerability, pharmacokinetics and efficacy of TUB-040 as monotherapy in patients with platinum-resistant high-grade ovarian cancer (PROC) or recurrent/refractory adenocarcinoma of non-small cell lung cancer (NSCLC). Based on the encouraging results, Tubulis plans to initiate pivotal studies and evaluate the candidate in earlier lines of therapy in ovarian cancer, as well as explore its inclusion in combination therapies and new solid tumor indications. The first data from the NSCLC cohort will be presented at a future medical conference.

About TUB-040 and the Tubutecan technology

Tubulis' lead antibody-drug conjugate (ADC), TUB-040, targets NaPi2b, an antigen that is highly overexpressed in ovarian cancer and lung adenocarcinoma. It consists of an IgG1 antibody targeting NaPi2b equipped with Tubulis' proprietary Tubutecan technology, connecting the topoisomerase I inhibitor, exatecan, through a cleavable linker system based on the company's proprietary P5 conjugation technology with a homogeneous DAR of 8. Using novel chemistry for cysteine-selective conjugation developed at FMP Berlin, the technology enables the development of stable, highly targeted ADCs that are optimized for the targeted delivery of the topoisomerase I inhibitor while minimizing systemic toxicity. 

About Tubulis

Tubulis develops tailor-made antibody-drug conjugates (ADCs) with superior biophysical properties. In preclinical models, the ADCs have already demonstrated targeted and sustained accumulation in tumors as well as long-lasting anti-tumor effects. The two lead programs in the growing pipeline are TUB-040 (targeting NaPi2b) and TUB-030 (targeting 5T4). Both programs are currently being evaluated in clinical trials for cancers in high-need solid tumor indications. For more information, visit: www.tubulis.com