Mersana Therapeutics, a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet need, and Synaffix, a Dutch biotechnology company, have entered into a license agreement in which Mersana gets access to Synaffix’s industry-leading site-specific GlycoConnect™ ADC technology.
Synaffix’s site-specific GlycoConnect™ ADC technology has consistently demonstrated an ability to improve both the safety and the efficacy profiles of ADC product candidates.
GlycoConnect™ , developed by Synaffix, is a platform technology utilizing proprietary enzymes and metal-free click conjugation to stably attach payloads specifically to the native glycan of any antibody, a privileged site for ADC applications.
This approach can be applied directly to an existing antibody without any DNA and or protein engineering and is compatible with all payload classes currently used in the development of ADCs. The growing experience of Synaffix and its collaboration partners continues to confirm the ability of GlycoConnect™ to consistently generate ADCs that are more effective and better tolerated when compared to the three major clinical-stage ADC conjugation technologies.
Figure 1.0: GlycoConnect, Synaffix’ robust chemoenzymatic technology platform, is a site-specific and stable antibody conjugation technology that allows for efficient antibody-to-ADC conversion by anchoring a payload to the antibody’s glycan at asparagine-297 (Asn-297). Human immunoglobulins, including Immunoglobulin G (IgG), the most prominent antibody in humans, are mainly glycosylated at the asparagine residue at position 297 (Asn 297) of the heavy chain CH2 domain. Synaffix’ process involves proprietary enzymatic N-glycan remodeling with one azide, forming an anchor point for the copper-free click attachment of a cytotoxic payload. The antibody remodeling includes a two-step approach. In the first step the enzyme trims the glycan. In the second step the enzyme installs a proprietary small molecule substrate bearing a functional handle, which will be used during subsequent conjugation. In this process, the proprietary azide-based enzymatic substrate preserves the high reactivity and selectivity afforded by conjugation via click chemistry. Since aromatically stabilized structures typically come with an order of magnitude higher stability than non-aromatic structures, the aromatically-stabilized triazole linker, formed during the second reaction, offers improved safety and efficacy profiles. As a result, a higher level of cytotoxic payloads reach the targeted cancer cell, increasing efficacy, while minimizing the potential of premature detachment in circulation and improving the safety profile. Courtesy: © 2010 – 2019 Synaffix. Used with permission.Collaboration
Under the terms of the agreement, which follows a research collaboration that was centered around multiple product candidates, Mersana has been granted a non-exclusive license to incorporate GlycoConnect™ into one of its investigational antibody-drug conjugates as well as an option to include the technology in additional programs.
Synaffix is eligible to receive upfront and milestone payments on a per-target basis with a projected total deal value of $295 million, plus royalties.
“After evaluating several site-specific conjugation platforms, we have chosen Synaffix’s GlycoConnect™ technology for use in future ADC candidates,” said Anna Protopapas, President and Chief Executive Officer of Mersana.
“We are excited about the potential of this technology as it is designed not to require additional antibody engineering or cell-line modifications, which would offer us the potential to create site-specific antibodies for use in our ADCs when required,” Protopapas added.
“We are particularly excited to enter into this agreement with a leading company in the field of ADCs such as Mersana,” noted Peter van de Sande, CEO of Synaffix.
“This collaboration is another testimony of the additional value that GlycoConnect™ is able to provide to already cutting-edge ADC technologies, thereby enabling novel medicines that are uniquely positioned to address areas of unmet medical need,” Van de Sande added.
Per the agreement, Mersana is responsible for the research, development, manufacturing and commercialization of any resulting ADC product while Synaffix will supply components that are specifically related to its proprietary GlycoConnect™ technology.
In addition to GlycoConnect™, Synaffix is also developing an ADC-enhancing HydraSpace™ technology, and toxSYN™ payloads, allowing the company to provide a fully complimentary technology platform that enables any company with an antibody to develop superior, proprietary ADC products.
