Tubulis, which spun out in 2019 from the Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP) in Berlin and the Ludwig Maximilians University (LMU) in Munich with the aim of expanding the therapeutic potential of antibody-drug conjugates (ADCs) for cancer and other disease indications, designs and develops transformative antibody-drug conjugates (ADCs) that are deeply integrated with disease biology and address key technological challenges as well as major unmet medical needs.
The company generates uniquely matched protein-drug conjugates by combining proprietary novel technologies with disease-specific biology, this approach allows the company scientists to expand the therapeutic potential of ADCs. Using their proprietary approach, the company expects that it can advance the development of a variety of conjugates, unlimited by indication.
Financing round
This week, the company confirmed the closure of a € 10.7 (US $ 12.62) million Series A financing round to accelerate the development of a new class of highly stable and efficient ADCs and to support the further growth of the company.
The financing round was co-led by BioMedPartners and High-Tech Gründerfonds (HTGF) with support from Seventure Partners, coparion, Bayern Kapital, and OCCIDENT alongside significant contributions by high net worth individuals and the founders.
“Tubulis’ objective is to use our dual-platform approach to generate uniquely matched and disease-specific ADCs that combine selective antibodies with effective payloads,” said Dominik Schumacher, Tubulis Chief Executive Officer, and co-founder.
“The funding committed by this experienced syndicate represents a validation of our technology and reflects the recent renaissance in ADC development in our industry. These proceeds will enable us to continue validating our platforms and to move our first two selected ADC candidates towards the clinic,” Schumacher added.
“Tubulis is tackling the limitations of current ADCs head-on and is helping to shape the future of ADCs for the treatment of a broad range of diseases. We look forward to supporting the team at Tubulis as they continue to build the company in a growing field with a high need for innovative solutions,” noted Michael Wacker, Partner at Swiss-based BioMed Partners, one of the companies involved in the Series A financing round which has established itself as one of the leading early-stage human healthcare investors in Europe.
Versatile approach
Tubulis’ uniquely versatile and customizable ADC technology portfolio consists of two proprietary technologies which are based on scientific discoveries made in the research groups of Prof. Christian Hackenberger (FMP), Prof. Heinrich Leonhardt (LMU) and Dr. Jonas Helma-Smets, who are all co-founders of the company. Jonas Helma-Smets also joined the company as Chief Scientific Officer.
Both platforms accommodate the complexities of modern ADC design with regard to protein format, payload potency, and payload hydrophobicity.
The company’s initial screening platform with fast conjugation (P5) to rapidly identify novel protein-drug combinations for therapeutic application includes a novel chemistry for cysteine-selective conjugation. It allows for ultra-stable ADC generation with unprecedented linker stability and chemical flexibility, enabling rapid lead identification. The cysteine-based conjugation method demonstrates an increased reaction selectivity and high chemical flexibility, enabling the fast and efficient conjugation of any antibody to any payload.
Following the screening phase, the selected best combinations are advanced via the company’s Tub-tag® platform technology, a short protein (α-tubulin) sequence fused to the protein of interest, was inspired by microtubule biology and adds a significant amount of stability to the ADC product candidates by modulating the antibody to provide a highly beneficial microenvironment for the payload. The human-derived nature of the Tub-tag® platform technology reduces the risk of unwanted immune responses. Combining these platforms addresses the main bottlenecks in the development of antibody-drug conjugates, creating uniquely stable therapeutic candidates with payload-driven toxicity, potentially broadening the spectrum of currently possible protein-drug combinations.[1][2]
In simple terms, based on the unique properties of unsaturated phosphorus scientists at Tubulis have developed a platform technology that makes it possible to link native proteins and antibodies to complex molecules, such as fluorescent dyes or drugs more easily and with better stability than ever before.
The technology, compared to superglue for ADCs, uses phosphonamidates to connect the desired modification – for example, a cytotoxic anticancer agent – exclusively to the amino acid cysteine, in a protein or antibody. Since cysteine is a very rare naturally occurring amino acid, the number of modifications per protein can be controlled quite effectively, which is essential for the construction of drug conjugates. In addition, phosphonamidates can easily be incorporated into complex chemical compounds. One of the unique features if the platform is that the resulting bond is also stable during blood circulation. Currently approved and commercially available ADCs cannot achieve this.
Based on the early development of the technology, scientists at Tubulis believe that phosphonamidate-linked drug transporters can be administered in lower doses, and that side effects can be further reduced compared ADCs with the same antibody and payload. Thus the technology has great potential to replace current methods in order to develop more effective and safer ADCs in the future.[1][2]
Following the Series A financing round, Tubulis is expected to prioritize the use of these technologies for internal drug discovery and development activities to generate uniquely matched antibody-drug conjugates, tailored to the respective indication.
The companies pipeline includes two ADCs in preclinical development (TUB-010 and TUB-020). Targets and Indications of these investigational agents have not yet been disclosed. In September 2019 Glycotope signed an agreement allowing the company non-exclusive access to Tubulis’ Tub-tag® technology for one of its ADC candidates.
Reference
[1] Kasper MA, Glanz M, Stengl A, et al. Cysteine-Selective Phosphonamidate Electrophiles for Modular Protein Bioconjugations. Angew Chem Int Ed Engl. 2019;58(34):11625-11630. doi:10.1002/anie.201814715
[2] Kasper MA, Stengl A, Ochtrop P, et al. Ethynylphosphonamidates for the Rapid and Cysteine-Selective Generation of Efficacious Antibody-Drug Conjugates. Angew Chem Int Ed Engl. 2019;58(34):11631-11636. doi:10.1002/anie.201904193
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