Swiss oncology-focusing Araris Biotech and Japan’s Chugai Pharmaceutical Co (a member of the Roche Group) have entered a Research Collaboration and Option to License Agreement under which Araris will use its proprietary linker-conjugation platform, AraLinQ™ to generate novel ADCs using antibodies against undisclosed targets provided by Chugai.
“We are excited to enter a collaboration with Chugai Pharmaceutical and look forward to working closely with the Chugai team and apply our ADC technology to develop next-generation ADCs with improved efficacy and tolerability,” explained Dragan Grabulovski, Ph.D., Chief Executive Officer and co-founder of Araris.
“This second collaboration with a large pharmaceutical company is a testimony of the attractiveness of our highly differentiated ADC platform and its potential to generate innovative ADCs with excellent pharmacokinetic properties and wide therapeutic index, incorporating dual- or triple-warheads into one step on native antibodies, without any requirement of prior antibody engineering,” noted Philipp Spycher, MSc, Ph.D., Founder Fellow at the Paul Scherrer Institute (PSI) in Villigen, Switzerland and Chief Scientific Officer and co-founder of Araris.
Under the terms of the agreement, Chugai will pay an upfront fee, fund all research activities and after exercising the option be solely responsible for the development, manufacturing and global commercialization activities. Upon achievement of certain development, regulatory and commercial milestones by Chugai after exercising the option, Araris will be eligible for potential milestone payments of approximately US $ 780 million, plus royalties on net sales of products.
Platform technology
Araris pioneered the development of best-in-class ADCs with superior design, high linker solubility and simple manufacturing that address the shortcomings of current generation ADCs. Foundational to its approach is its novel, proprietary ADC linker platform that enables conjugation of two or more different payloads to an “off-the-shelf” antibody at a specific site in one step without re-engineering the antibody.
The proprietary conjugation technology called AraLinQ™ enabled best-in-class ADCs with significantly enhanced efficacy and tolerability.
The technology was developed by a team of researchers at Araris who pioneered the use of microbial transglutaminase (MTG) for the chemo-enzymatic modification of tumor targeting antibodies with different radionuclides, fluorescent dyes and toxins via the residue glutamine 295 (Q295) on the Fc-fragment of antibodies.[1][2][3]
Stability of an antibody-drug conjugates is key to maximize payload delivery to the targeted site and to avoid dose-limiting, excessive toxicities and achieve a wide therapeutic index. [1] By exploiting native Q295 for site-specific payload attachment in one-step, researchers at Araris have been able to develop conjugates that consistently showed to result in ADCs with an antibody-like exposure profile even at high drug-load without the use of any polymeric solubility enhancers.
AraLinQ™ can be applied directly to any existing off-the-shelf antibody without engineering and enables the generation of single or multi-payload ADCs from off-the-shelf linker-payloads.
“Our technology enables site-specific conjugation of various payloads to ready-to-use antibodies in a simple process that allows us to create more effective and safer ADCs. Homogeneous, site-specifically conjugated antibodies have shown to result in ADCs with improved efficacy and tolerability compared to stochastically conjugated ADCs, but precisely controlling the drug load and attaching multiple payload moieties on the antibody has been a challenge,” Spycher said.
“By demonstrating precise control over drug loading and enabling the attachment of multiple payloads, Araris is overcoming these challenges and providing new technologies for ADC design. We’re pleased to see that our ADCs were well tolerated overall even at high doses, and the impressive efficacy demonstrated by our ADCs underscores the potential of this approach,” he concluded.
Reference
[1] Wehrmüller JE, Frei JC, Hechler T, Kulke M, Pahl A, Béhé M, Schibli R, Spycher PR. Site-Specific Modification of Native IgGs with Flexible Drug-Load. Chembiochem. 2024 Sep 21:e202400511. doi: 10.1002/cbic.202400511. Epub ahead of print. PMID: 39305147.
[2] Jeger S, Zimmermann K, Blanc A, Grünberg J, Honer M, Hunziker P, Struthers H, Schibli R. Site-specific and stoichiometric modification of antibodies by bacterial transglutaminase. Angew Chem Int Ed Engl. 2010 Dec 17;49(51):9995-7. doi: 10.1002/anie.201004243. PMID: 21110357.
[3] Dennler P, Chiotellis A, Fischer E, Brégeon D, Belmant C, Gauthier L, Lhospice F, Romagne F, Schibli R. Transglutaminase-based chemo-enzymatic conjugation approach yields homogeneous antibody-drug conjugates. Bioconjug Chem. 2014 Mar 19;25(3):569-78. doi: 10.1021/bc400574z. Epub 2014 Feb 12. PMID: 24483299.
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