Next-gen ADCs: Tubulis sets new standard in cancer treatment

Tubulis is making significant strides in the rapidly evolving field of cancer therapies, pioneering the development of next-generation antibody-drug conjugates (ADCs) that target and treat solid tumours.

As ADCs continue to show great promise, Tubulis, under the leadership of CEO and co-founder Dominik Schumacher, is at the forefront of pushing beyond the limitations of existing treatments. With cutting-edge technologies, a dedicated team, and a clear vision, the company is set to transform cancer care.

In this interview with Drug Target Review, Schumacher shares insights into Tubulis’ journey, its current and future ADC programmes, and its pivotal role in shaping the future of cancer treatment.

A visionary leader in biotech

Dominik Schumacher’s success and vision for Tubulis were recognised early on. In 2019, he was named one of MIT’s Innovators Under 35, a prestigious award that highlighted his ability to combine scientific excellence with entrepreneurial drive. Under his leadership, Tubulis has emerged as a leader in the ADC field, constantly refining and advancing its proprietary technologies to explore the true therapeutic potential of these powerful drug conjugates.

One of the most impressive aspects of Tubulis’ journey is its rapid progress in advancing its ADC candidates into clinical trials. In just a year, the company brought its second ADC into the clinic. According to Schumacher, the company’s success is driven by a combination of factors: “First and foremost, this was made possible by our outstanding team, whose hard work and expertise enabled the rapid progress of our two clinical programmes. Another critical factor is our proprietary suite of platform technologies, which provide a robust and flexible foundation for innovative ADC design.“ These proprietary technologies enable Tubulis to design ADCs that deliver powerful anti-cancer agents precisely to the tumour site while minimising off-site toxicity, thus improving the overall therapeutic index.

TUB-030: an ADC targeting solid tumours

At the heart of Tubulis’ current clinical programmes is TUB-030, a highly innovative ADC targeting 5T4, a cancer-associated antigen expressed in a wide range of solid tumour indications. TUB-030 represents a breakthrough in ADC design, combining a highly specific IgG1 antibody targeting 5T4 with exatecan, a potent topoisomerase I inhibitor, connected through a cleavable linker system based on Tubulis’ proprietary P5 conjugation technology. A topoisomerase I inhibitor is a type of drug that interferes with the activity of topoisomerase I, an enzyme that plays a critical role in DNA replication and transcription.

“Preclinical pharmacokinetic analysis showed that TUB-030 efficiently delivers its payload to the tumour while reducing off-site toxicities,” says Schumacher. The preclinical results demonstrated strong anti-tumour efficacy and a favourable safety profile, even at lower target expression levels. This has given Tubulis confidence that TUB-030 could offer a new and highly effective treatment option for patients with solid tumours, with the potential to provide durable responses and improve overall survival.

The unique chemistry behind TUB-030’s design enables the ADC to maintain a high level of stability, ensuring that the drug payload is delivered specifically to the tumour site. This highly controlled drug-to-antibody ratio (DAR) of eight maximises therapeutic efficacy while reducing unwanted side effects.

Translating preclinical success to clinical potential

While the preclinical data for TUB-030 is promising, Schumacher is cautious about translating these findings directly into the clinic. “We are very excited by the strong preclinical data we have seen for TUB-030 to date. We are hoping to translate these findings into the clinic, but at this moment, it is too early to make any assumptions,” he explains.

However, the robust preclinical data has provided a solid foundation for Tubulis to be confident in the clinical potential of TUB-030

Pushing the boundaries of ADC innovation

Tubulis is not just another player in the ADC field. The company is driving innovation by expanding the possibilities of what ADCs can achieve. While many companies have focused on improving linker-payload chemistry – the chemical connection between the linker and payload in an antibody-drug conjugate (ADC) – Tubulis is taking a broader, forward-thinking approach. “Innovation in the ADC space has largely focused on linker-payload chemistry, but at Tubulis, we are pushing the boundaries even further. Our novel technologies go beyond the conventional chemical payload conjugation, unlocking novel payload classes that were previously inaccessible.”

This commitment to change allows Tubulis to design ADCs that are not constrained by the limitations of traditional approaches. By exploring new payload mechanisms and linker technologies, the company is expanding the therapeutic potential of ADCs, ensuring it can overcome the emerging resistances seen with conventional payloads. Tubulis’ novel technologies provide the flexibility to create targeted therapies that address specific disease biology and pathophysiology, ultimately broadening the range of tumours that can be treated with ADCs.

Schumacher highlights the importance of flexibility in ADC design, saying, “With our suite of proprietary technologies, we can provide a new level of flexibility to ADC design, enabling the creation of novel protein-drug combinations following the biology and the underlying pathophysiology of a specific disease.”

The future of Tubulis

Schumacher envisions Tubulis maintaining its leadership in the ADC space, with a clear focus on advancing additional ADC candidates and refining its platform technologies. “Over the next decade, we aim to introduce several novel ADCs that provide greater precision, efficacy and safety,” he shares.

The ADC field is constantly evolving, with new advancements emerging in linker technologies and payload classes. However, resistance to ADC treatments remains a challenge. Schumacher believes that the next wave of developments in the ADC space will focus on overcoming resistance mechanisms and developing alternative payload classes, such as degrader-based ADCs. Tubulis’ Alco5 technology, which enables the conjugation of previously inaccessible hydroxy-group-containing payloads, is an example of how the company is addressing this challenge.

“We believe the next wave of innovation will concentrate on alternative payload mechanisms, such as degrader-based ADCs, as a sequential approach,” Schumacher adds. This approach holds the potential to tackle the growing problem of ADC resistance and expand the applicability of these treatments to a wider range of cancer types.

In the long term, he sees ADCs becoming a standard-of-care strategy in oncology, including in early treatment lines.

“In the long term, we envision ADCs becoming a versatile and effective standard-of-care strategy, including in early treatment lines, providing a safe, efficient and durable option for a broad range of tumour types – and potentially even expanding to indications beyond oncology.”

As the ADC landscape continues to evolve, Tubulis is well positioned to remain at the forefront of this exciting field, with a commitment to improving patient outcomes and ultimately changing the way cancer is treated.