MUNICH--(BUSINESS WIRE)--Tubulis today presented comprehensive preclinical data on its two lead antibody-drug conjugate (ADC) candidates TUB-030 and TUB-040 at this year’s Annual Meeting of the American Association for Cancer Research (AACR) in San Diego. The poster presentations contained preclinical data, highlighting the ability of the two next-generation Tubutecan ADCs to create effective and durable responses even in low target-expressing tumor mouse models. Tubulis is leveraging a proprietary suite of platform technologies to build a pipeline of uniquely matched ADC candidates that combine the right targeting molecule, conjugation chemistry and payload to deliver the true therapeutic value of the ADC approach. The company’s lead candidates, both targeting solid tumor indications, are in late-stage preclinical testing, with TUB-040 ready for clinical evaluation.
"These compelling preclinical data sets for both of our lead ADC candidates, TUB-030 and TUB-040, support how our proprietary platforms create ADCs with unique biophysical properties allowing for continued and durable on-tumor delivery of the payload. The in vivo studies have demonstrated that both candidates show strong, long-lasting anti-tumor activity, even at lower expression levels of the respective targets," said Jonas Helma-Smets, Chief Scientific Officer of Tubulis. "Our ADCs are highly differentiated compared to other ADCs on the market and we look forward to translating these findings into the clinic with the goal of improving overall survival and duration of response in patients across a broad range of solid tumors. Starting with TUB-040, we aim to initiate first clinical trials this year and thereby provide clinical proof-of-concept for our next-generation ADCs and our differentiated platform approach to ADC design."
Both ADC candidates are comprised of a humanized, target-specific, Fc-silenced IgG1 antibody conjugated to the topoisomerase-1 inhibitor Exatecan with Tubulis’ Tubutecan linker-payload platform via the proprietary P5 conjugation platform, resulting in highly stable and homogenous drug-to-antibody-ratio of 8 (DAR8) ADCs. Compared to maleimide-conjugated ADCs, TUB-030 and TUB-040 both showed superior stability and minimal loss of linker-payload conjugation.
Highlights of Tubulis’ preclinical data presented at AACR 2024:
TUB-040
- TUB-040 is built with novel Tubutecan linker-payload chemistry and superb biophysical properties, targeting Napi2b, a highly overexpressed antigen in ovarian cancer and lung adenocarcinoma
- The ADC candidate is highly stable and highly inert in circulation, enabling powerful and continued on-tumor delivery of the payload, leading to complete eradication of tumors with a low dose single treatment in multiple ovarian cancer mouse models
- Enabled by the differentiated Tubutecan linker-payload and strong bystander activity, TUB-040 showed significantly better durability of antitumor activity in preclinical models compared to lifastuzumab vedotin
- In ovarian cancer and non-small-cell lung cancer (NSCLC) patient derived xenograft mouse models, treatment with TUB-040 led to robust long-lasting tumor regressions
- Repeat-dose toxicology studies of TUB-040 in non-human primates demonstrated that TUB-040 was well tolerated with minor and reversible adverse effects
TUB-030
- TUB-030 is built with novel Tubutecan linker-payload chemistry and superb biophysical properties, targeting 5T4, a tumor-associated antigen expressed in a broad range of solid tumors
- The ADC candidate demonstrated target-specific cytotoxicity as well as strong bystander activity, facilitating the destruction of cells that do not express the target antigen but are in the direct vicinity of the targeted tumor cell, thereby broadening the effect of the ADC
- A single treatment with TUB-030 was shown to eliminate tumors in a triple negative breast cancer mouse model, whereas PF06263507, a clinically tested comparator ADC led to re-growth of tumors.
- In over 25 patient derived xenograft mouse models of various types of cancer, TUB-030 showed high efficacy rates even at low 5T4 expression levels and achieved long-lasting and durable anti-tumor activity
- TUB-030 was well tolerated in non-human primates and showed highly restricted binding to normal fresh frozen human tissues
The full abstracts were published in an online-only proceedings supplement to the AACR journal, Cancer Research in March and can be accessed here.
About Tubulis
Tubulis generates uniquely matched protein-drug conjugates through the combination of novel proprietary technologies and disease-specific biologic insight. Our goal is to expand the therapeutic potential of antibody-drug conjugates (ADCs) by increasing design flexibility while overcoming constraints of toxicity, efficacy and indication. Tubulis will build new conjugates to fill its growing pipeline and will continue to collaborate with industry partners to usher in a new ADC era and deliver better outcomes for patients. Visit www.tubulis.com or follow us on LinkedIn.
