Lonza's Synaffix Collaborates with BigHat Biosciences on the Development of a Machine Learning-Designed ADC

• Commercial license to Synaffix technologies follows a series of successful initial preclinical proof of concept studies
• Collaboration underscores Lonza's commitment to helping customers deliver innovative new therapies to patients by offering a comprehensive service offering for differentiated ADCs
• BigHat's artificial intelligence (AI)/machine learning (ML)-powered antibody design platform, Milliner™ was used to design a highly differentiated antibody that was paired with Synaffix's GlycoConnect™, HydraSpace® and toxSYN® ADC technologies to generate a next-gen ADC

AMSTERDAM and BASEL, Switzerland, Nov. 4, 2024 /PRNewswire/ -- Synaffix B.V. ("Synaffix"), a Lonza company (SWX: LONN) focused on commercializing its clinical-stage platform technology for the development of antibody-drug conjugates (ADCs) with best-in-class therapeutic index, today announced that it has licensed its ADC technology to BigHat Biosciences, Inc. ("BigHat"). BigHat will combine Synaffix technology with its world-class ML antibody design platform for the development of a new ADC pipeline program. 

Under the terms of the agreement, BigHat will receive target-specific access to Synaffix's late-clinical stage, site-specific ADC technology platform, which enables the transformation of antibodies into proprietary, best-in-class ADC products. As a result of Lonza's acquisition of Synaffix in June 2023, BigHat will also gain access to Lonza's end-to-end ADC offering. This DNA-to-IND offering enables drug developers to seamlessly receive all necessary cGMP/non-cGMP ADC batches leading up to the first clinical trial under a single quality system encompassing all critical development and manufacturing activities, including the production of the antibody, bioconjugation, and drug product filling.

BigHat's AI/ML-powered antibody design platform, Milliner™, integrates a synthetic biology-based high-speed wet lab with state-of-the-art ML technologies into a full-stack antibody discovery and engineering platform, to engineer antibodies with more complex functions and better biophysical properties. This approach reduces the difficulty of designing antibodies and other therapeutic proteins to tackle conditions ranging from chronic illness to life-threatening disease, while also massively speeding up candidate discovery and validation.

The collaboration with Synaffix/Lonza is instrumental to advancing BigHat's next-gen ADC program, which is at IND-enabling stage and is on track to be BigHat's first clinical stage program. BigHat's next-gen ADC was optimized on BigHat's Milliner platform for maximum payload delivery to tumor cells and optimal drug-like-properties. The incorporation of Synaffix's GlycoConnect™, HydraSpace® and toxSYN® ADC technologies is intended to further improve the safety and efficacy of Big Hat's next-gen ADC.

Peter van de Sande, Head of Synaffix, said: "The ADC space continues to develop and evolve, and our collaboration with BigHat exemplifies the continued strength and appeal of our best-in-class ADC technology. We are excited to be at the forefront of next-generation ADC R&D by joining forces with BigHat and its AI/ML-enabled antibody discovery and development platform, BigHat is the ideal partner for Synaffix to collaborate with. We look forward to supporting BigHat with every step in the ADC development and manufacturing process under the Lonza umbrella."

Jean-Christophe Hyvert, President, Biologics, Lonza, added: "We are pleased to announce this collaboration with BigHat for its next-gen ADC molecule, which shows how drug developers can benefit from a fully integrated suite of services across our Biologics division. The Lonza network has continued to adapt to the evolving ADC landscape, including the recent addition of a highly potent vial fill capability at our Stein (CH) facility. This dedicated ADC drug product capacity expansion completes our offer for comprehensive, end-to-end development and manufacturing services for ADCs, simplifying the path from DNA-to-IND and beyond for our customers."

Mark DePristo, CEO at BigHat Biosciences, commented: "BigHat is leveraging our AI-driven antibody design platform, Milliner™, to develop advanced biologics that provide safer and more effective treatments for difficult-to-treat cancers. We are excited to combine Synaffix's conjugation and linker-payload technologies with our custom-designed antibody to create a next-generation ADC for patients with high unmet medical need."

About Synaffix

Synaffix B.V. is a biotechnology company that enables ADC product candidates using its clinical-stage, site-specific ADC technology platform based on GlycoConnect™, HydraSpace® and toxSYN® technologies, that together enable any company with an antibody to develop proprietary best-in-class ADC products under a single license from Synaffix.

The Synaffix platform enables a rapid timeline to clinic due to the established supply chain of technology components. Synaffix holds granted patents to its technology. The business model of Synaffix is target-specific technology out-licensing, as exemplified through its existing deals with ADC Therapeutics, Mersana Therapeutics, Shanghai Miracogen (acquired by Lepu Biopharma), Innovent Biologics, Kyowa Kirin, Genmab, Macrogenics, Amgen, Hummingbird Biosciences, Chong Kun Dang Pharma, ABL Bio, and SOTIO Biotech.

Synaffix was fully acquired by Lonza in June 2023.

About The Synaffix ADC Platform Technology

Synaffix's proprietary ADC technology platform consists of GlycoConnect™, GlycoConnect™ High DAR Technology, HydraSpace®, and toxSYN® technologies. These technologies are aimed at enabling best-in-class ADCs from any antibody, with significantly enhanced efficacy and tolerability. 

GlycoConnect™ clinical-stage conjugation technology exploits the native antibody glycan for site-specific and stable payload attachment and is tunable to DAR1, DAR2 or DAR4 formats. The extension of GlycoConnect™ with High DAR Technology enables ADCs with high drug loading (6, 8 and above), while retaining high drug substance homogeneity and therapeutic index. HydraSpace® clinical-stage compact and highly polar spacer technology is designed to further enhance therapeutic index, particularly with hydrophobic payloads. toxSYN® linker-payload platform spans key, validated MOAs for ADC product development. This includes potent topoisomerase 1 inhibitor (SYNtecan E™), DNA damaging agents (SYNeamicin D™, SYNeamicin G™ and SYN-PNU™), ⍺-Microtubule (SYNtansine™) and β-Microtubule (SYNstatin E™ and SYNstatin F™) inhibitors as well as several unlaunched proprietary linker-payloads that were generated through the ongoing innovative efforts of the Synaffix R&D team.

The newest proprietary linker-payload, "SYN-PNU™" is part of the established and expanding toxSYN™ linker-payload portfolio.  SYN-PNU™ represents (based on pre-clinical models) a significantly potency-attenuated and better tolerated version of PNU-159,682, to enable enhanced administered dose levels and competitive therapeutic properties versus ADCs prepared using the original molecule. The reference compound (PNU-159,682) is metabolite of the anthracycline Nemorubicin and represents a highly potent DNA topoisomerase II inhibitor.

The combination of these three technologies provides developers with a "one stop" and easy-to-use ADC technology platform, allowing any antibody developer to develop its own proprietary ADC and any ADC developer to expand its pipeline further and increase its competitive position.

About Lonza

Lonza is one of the world's largest healthcare manufacturing organizations. Working across five continents, our global community of around 18,000 colleagues helps pharmaceutical, biotech and nutrition companies to bring their treatments to market. United by our vision to bring any therapy to life, we support our customers with a combination of technological insight, world-class manufacturing, scientific expertise, process excellence and innovation. Our work enables our customers to develop and commercialize their therapeutic discoveries, allowing their patients to benefit from life-saving and life-enhancing treatments.

Our business is structured to meet our customers' complex needs across four divisions: Biologics, Small Molecules, Cell & Gene, and Capsules & Health Ingredients. Our company generated sales of CHF 3.1 billion with a CORE EBITDA of CHF 893 million in Half-Year 2024. Find out more at www.lonza.com

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About BigHat Biosciences

BigHat Biosciences is a biotechnology company with an AI/ML-guided antibody discovery and development platform, capable of engineering antibodies with more complex functions and better biophysical properties. By using its ML-powered antibody design program to iteratively improve antibodies through sequential design-build-test cycles. The system measures the biophysical properties and impact on disease activity using cell-based or other functional assays, which replicate in vivo disease processes.

BigHat is a Series B biotech outside San Francisco with a team-oriented, inclusive, and family-friendly culture. Our pipeline of wholly-owned and partnered therapeutic programs focus on indications with high unmet need, such as cancer and inflammation. BigHat has raised over $100M from top investors, including Section 32, a16z, and 8VC. To learn more about us, visit https://www.bighatbio.com and follow @BigHatBio on LinkedIn and Twitter.