On January 21, 2026 Tubulis reported the publication of preclinical proof-of-concept data for its novel Alco5 conjugation platform in Nature Communications. The paper describes the company’s novel antibody-drug conjugate (ADC) technology and highlights its ability to link antibodies with an expanded set of previously inaccessible hydroxy-containing payloads. This new chemical concept has the potential to open new therapeutic avenues in cancer treatment and counteract resistance by expanding ADC’s payload spectrum with novel modes of action (MOAs) including protein degradation while preserving favorable ADC properties.
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The full publication titled "Expanding the payload scope in antibody-drug conjugates by delivery of hydroxy-containing drugs through self-immolative phosphoramidates" is available here.
"Our Alco5 linker platform represents a key step forward in unlocking the full potential of ADCs to drive meaningful patient benefit in oncology," commented Dr. Jonas Helma-Smets, Chief Scientific Officer and Co-Founder of Tubulis. "The broad applicability and excellent safety and efficacy profile will enable us to explore novel antibody-drug combinations, further solidifying Tubulis’ position at the forefront of scientific ADC breakthroughs."
Tubulis designed the Alco5 linker system to expand the payload spectrum beyond the three MOAs currently used in approved ADCs, specifically tubulin-inhibition, topoisomerase-I-inhibition and DNA damage-induction. The phosphoramidate-based Alco5 system enables safe and stable linkage to a broad range of structurally diverse alcohols that can be tracelessly released within the cytosol of target cancer cells. The resulting ADCs have a high and homogenous drug-to-antibody ratio (DAR) and demonstrated superior serum stability, in vivo efficacy and antibody-like pharmacokinetic profiles compared to approved topoisomerase-I-inhibitor-based ADCs.
Key data from the publication:
The Alco5 linker system was successfully applied to a wide range of ten hydroxy-containing antiproliferative agents, including the creation of ADCs carrying nucleoside analogues, or elongation factor-inhibitors for which this is the first time an in vitro potency was described.
All payloads with activity below 1 nM in the unconjugated state also showed activity when delivered by an ADC, clearly demonstrating the broad applicability of the described linker system to efficiently deliver payloads with chemically diverse hydroxyl groups.
Alco5-conjugated payloads demonstrated strong and selective anti-tumor effect in vitro and in vivo showcasing the potential to widen the therapeutic window of hydroxy-containing drugs by stably and durably delivering them to the tumor over a long period of time after a single administration.
"Publishing our findings in such a highly regarded journal underlines the potential of our novel linker technology to expand the horizons of ADC design," said Dr. Marc-André Kasper, Vice President Chemistry and Early Development at Tubulis. "We are highly encouraged by these results and look forward to investigating novel candidates based on the Alco5 technology to provide novel solutions for patients while addressing the growing resistance development to current ADCs."
(Press release, Tubulis, JAN 21, 2026, View Source [SID1234662148])