Tubulis Advances ADC TUB-030 into Clinical Trials for Advanced Solid Tumors
Tubulis, a biopharmaceutical company focused on antibody-drug conjugates (ADCs), announced a significant milestone today with the dosing of the first patient in its Phase I/IIa clinical trial, 5-STAR 1-01 (NCT06657222). This study evaluates Tubulis’ second ADC candidate, TUB-030, in patients with advanced solid tumors. TUB-030 targets 5T4, an oncofetal antigen present in a wide array of solid tumors, using Tubulis’ cutting-edge Tubutecan linker-payload platform. This innovative platform is designed to enhance the precise and sustained delivery of therapeutic agents directly to the tumor, potentially improving treatment efficacy and safety.
A Step Forward in ADC Development
The commencement of this clinical trial marks a significant achievement for Tubulis, as the company progresses with its second ADC candidate in clinical evaluation within less than a year. The announcement highlights Tubulis’ commitment to driving innovation in the ADC space, an area that holds considerable promise for cancer treatment. By advancing two differentiated ADC molecules into clinical testing so quickly, Tubulis is positioning itself as a leader in the development of next-generation cancer therapies.
Dominik Schumacher, PhD, the Chief Executive Officer and Co-founder of Tubulis, commented on this accomplishment, emphasizing the company’s rapid progress. “This milestone for TUB-030 demonstrates our ability to execute on our strategy to advance innovative programs into our proprietary pipeline and rapidly bring them into the clinic,” he stated. “As an organization, Tubulis has made a large step forward with two differentiated ADC molecules in clinical evaluation in less than a year. Our goal is to continue being an innovation driver in the field by delivering on the transformative potential of our platforms for patients.”
The 5-STAR 1-01 Trial: A Comprehensive Evaluation
The 5-STAR 1-01 trial is a multicenter, first-in-human study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of TUB-030 as a monotherapy in patients with advanced solid tumors. The trial will be conducted at several sites across the US and Canada and will enroll up to 130 patients.
The trial is structured in two phases: Phase I and Phase IIa. Phase I focuses on dose escalation to establish the safety profile of TUB-030, identify the maximum tolerated dose (MTD), and determine the optimal dose for further evaluation in patients with advanced solid tumor types. Phase IIa will then assess the safety and tolerability of the drug at the optimized dose and explore its preliminary efficacy in a range of selected tumor indications.
TUB-030’s potential to address solid tumors stems from its targeting of the 5T4 antigen, which is expressed in a broad spectrum of cancers. By targeting this oncofetal antigen, TUB-030 is designed to selectively deliver cytotoxic agents to the tumor cells, while minimizing damage to healthy tissues. This approach is expected to enhance the therapeutic efficacy of ADCs while reducing the side effects typically associated with conventional chemotherapy.
A Promising ADC with Strong Preclinical Data
The preclinical data supporting TUB-030 is robust, with a range of studies demonstrating the compound’s stability, safety, and potential for inducing strong anti-tumor responses. TUB-030 is composed of a humanized IgG1 antibody that targets 5T4, which has been engineered to have an Fc-silenced modification to reduce potential immune activation. The antibody is conjugated with Tubulis’ proprietary Tubutecan technology, which is based on a unique P5 conjugation chemistry and exatecan, a topoisomerase-1 inhibitor that disrupts DNA replication in cancer cells.
In preclinical studies, TUB-030 has shown remarkable efficacy in several tumor models, including triple-negative breast cancer, where a single dose of the drug was able to completely eliminate tumors in mouse models. This anti-tumor activity was observed even at relatively low levels of 5T4 expression, which is an important finding given that many solid tumors do not overexpress this target antigen.
Additionally, the preclinical data demonstrated that TUB-030 has an excellent safety profile, with minimal loss of linker-payload conjugation during treatment, ensuring that the drug remains stable and effective throughout its delivery to the tumor. The compound has also shown a strong bystander effect, meaning that TUB-030 can impact neighboring tumor cells even if they do not directly express the 5T4 antigen, further enhancing its potential therapeutic value.
Günter Fingerle-Rowson, MD, PhD, Chief Medical Officer at Tubulis, explained the significance of the preclinical data, stating, “Building on our strong preclinical efficacy and safety data, we are expecting that targeting 5T4 with our high-performance ADC technology may offer a new precision therapy option for a variety of solid tumor indications. With our differentiated target, a strong bystander effect, and efficient and durable target engagement via the Tubutecan platform, TUB-030 provides the potential to induce robust anti-tumor activity in 5T4-expressing tumors.”
Tubulis’ Proprietary Technology Platform
One of the key differentiators for TUB-030 is Tubulis’ proprietary Tubutecan linker-payload platform. This innovative platform enables the development of ADCs with superior biophysical properties, allowing for the precise delivery of potent cytotoxic payloads directly to tumor cells. By using the Tubutecan technology, Tubulis is able to enhance the stability of the ADC, ensuring that the therapeutic payload is not prematurely released into the bloodstream, which could cause off-target effects. This approach improves the overall safety and efficacy of ADCs and offers significant promise for the treatment of solid tumors.
The Tubutecan platform is also designed to support the development of ADCs targeting a range of tumor-specific antigens, allowing Tubulis to build a pipeline of therapies for multiple cancer indications. This flexibility is a critical component of Tubulis’ strategy to address the unmet needs of patients with advanced cancers, where current treatment options are limited and often accompanied by significant side effects.
