On March 5, 2024 Tubulis reported that two abstracts with comprehensive preclinical data on their next-generation antibody-drug conjugate (ADC) candidates TUB-030 and TUB-040, have been accepted for poster presentations at the Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper), taking place April 5-10, 2024 in San Diego (Press release, Tubulis, MAR 5, 2024, View Source [SID1234640834]).

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Tubulis is building a pipeline of uniquely matched ADCs, tailored to respective disease biology by leveraging the company’s proprietary suite of platform technologies to combine the right targeting molecule, conjugation chemistry and payload. TUB-030 is directed against the tumor-associated antigen 5T4 which addresses a wide range of solid tumor indications. TUB-040 targets Napi2b, a well-characterized target in ovarian and lung cancer. Both ADC candidates are optimized for long-lasting, durable tumor engagement and minimal off-target toxicity.

"Our novel technologies allow us to push the boundaries of ADC design to fully leverage the biology of well-understood therapeutic targets as well as unlock less-validated ones to create treatments that deliver meaningful patient benefit. The results we will present at the AACR (Free AACR Whitepaper) Annual Meeting will highlight the preclinical differentiation of our two lead candidates, TUB-030 and TUB-040. We believe that these two ADC candidates hold great potential to effectively enable durable responses and prolong overall survival in patients with a broad range of solid tumors while maintaining a significant safety and tolerability profile," said Jonas Helma-Smets, Chief Scientific Officer of Tubulis. "We look forward to further investigating the impact these two candidates can make in the clinic."

Details of the poster presentations:

TUB-030 Poster Information

Title: Enabling 5T4 for targeted cancer therapy: TUB-030, a novel ADC built with ethynylphosphonamidate conjugation chemistry, shows long-lasting anti-tumor activity via Topoisomerase-I inhibition with an optimized therapeutic index
Presenter: Jonas Helma-Smets, CSO of Tubulis
Session Category and Title: Immunology – Antibody-Drug Conjugates
Session Date and Time: Monday, Apr 8, 2024, 1:30 PM – 5:00 PM PT
Location: Poster Section 2
Abstract Number: 2623

The poster will highlight the pre-clinical proof-of-concept data for TUB-030, an ADC that targets the oncofetal 5T4 antigen. 5T4 is a tumor-associated protein that is overexpressed in various types of cancers, including bladder, lung, breast, stomach, esophagus, head and neck, colon, and ovarian cancer. Tubulis’ ADC candidate differs from previous ADCs targeting 5T4 by implementing several layers of differentiation in terms of antibody, payload and conjugation technology. It combines the company’s proprietary P5 conjugation technology with its Tubutecan topoisomerase-I payload platform, resulting in a homogenous DAR (drug-antibody-ratio) of 8. TUB-030 has shown strong cytotoxicity towards cancer cells from different tumor indications with a broad range of 5T4 expression levels. Pharmacokinetic analysis further demonstrated the highly stable profile of TUB-030, enabling the efficient delivery of the payload to the tumor.

TUB-040 Poster Information

Title: TUB-040, a novel Napi2b-targeting ADC built with ethynylphosphonamidate conjugation chemistry, demonstrates high and long-lasting anti-tumor efficacy via Topoisomerase-I inhibition and excellent tolerability predictive of a wide therapeutic window in humans
Presenter: Jonas Helma-Smets, CSO of Tubulis
Session Category and Title: Immunology – Antibody-Drug Conjugates
Session Date and Time: Monday, Apr 8, 2024, 1:30 PM – 5:00 PM PT
Location: Poster Section 2
Published Abstract Number: 2622

The poster will provide a detailed overview of the preclinical proof-of-concept for TUB-040. The ADC candidate is directed against Napi2b, an antigen highly overexpressed in ovarian cancer and lung adenocarcinoma. Its IgG1 antibody targeting Napi2b is connected to its payload, the Topoisomerase I inhibitor Exatecan through a cleavable linker system. The company’s P5 conjugation technology was used to build TUB-040 with a homogenous DAR of 8. TUB-040 induces DNA damage and cell death, without causing unspecific uptake and cytotoxicity in healthy, target-negative cells. Moreover, Pharmacokinetic analysis showed that TUB-040 is highly stable, thus efficiently delivering its payload to the tumor while reducing offsite toxicities.

The full abstracts will be published on March 22, 2024, in an online-only proceedings supplement to the AACR (Free AACR Whitepaper) journal, Cancer Research. The company will issue a press release detailing the full preclinical data following the presentation at AACR (Free AACR Whitepaper).