Cambridge based Mersana Therapeutics and Recepta Biopharma, a clinical stage Brazilian biotechnology company, have entered into an exclusive license agreement in which Mersana will use its Fleximer® technology, a proprietary, biodegradable, hydrophilic polymer, to develop and commercialize an immunoconjugate with the undisclosed cancer antibody licensed from Recepta.
Researchers have shown that Fleximer-based immunoconjugate molecules offer superior efficacy, including with targets previously considered not amenable to antibody-drug conjugate approaches.
Unique approach
Mersana’s approach can dramatically improve drug solubility and pharmacokinetics, reduce immunogenicity and optimize drug load.
Furthermore, the Fleximer polymer, which serves as the backbone for the company’s drug conjugates, is uniquely biodegradable, well tolerated with a favorable safety profile and has been clinically validated.
One of the unique features is that the size of the backbone can, based on the type and quantity of therapeutic payloads, as well as the nature of the targeting protein being attached, be customized to the required circumstances.
Another feature is that Mersana’s scientists can determine which and how many linkers to use to attach the payload to the Fleximer backbone. Using a diverse array of linker chemistries allows them to arm drug conjugates with significantly higher loads of anti-cancer agents than conventional antibody-drug conjugate technologies, as well as to potentially arm a single immunoconjugate with a combination of payloads. These custom-designed linkers allow scientists to control the rate, mechanism and localization of drug release, potentially increasing efficacy and minimizing off-target side effects.
Linker technology
Using a chemically distinct linker from those used to attach the therapeutic payload, scientists at Mersana can attach an antibody, or alternative targeting moiety such as an antibody fragment, to the backbone. What makes the Fleximer backbone unique, is the ability to attach a variety of targeting agents, allowing scientists to choose the one that will most effectively reach, bind to and penetrate the tumor cell, while sparing healthy cells. By using separate linker chemistries to attach the targeting agent and drug payload, scientists are further able to choose the best linkers for each required task.
Overcoming limitations
The Fleximer platform developed by Mersana represents a next generation approach in the development of antibody-drug conjugates, allowing their scientists to overcome many of the limitations of current ADC-technologies. Based on the unique technology as well as the linker chemistries, scientists at the company can custom design an antibody-drug conjugate with a significant higher drug-to antibody ratios (DAR; 20+ versus 3-4 with traditional technologies), with a unique combination of properties, resulting in higher efficacy in head-to-head studies aimed specifically at attacking a particular type of cancer.
Agreement
Under the terms of the agreement, Recepta will provide Mersana exclusive rights to its novel monoclonal antibody to an undisclosed target, and Mersana, in turn, will leverage Fleximer to develop an immunoconjugate against the target. Financial terms of the agreement include an upfront payment and subsequent payments to Recepta, which together could total $86 million plus royalties if certain development, regulatory and commercial milestones are achieved. Mersana will conduct and fund clinical development and regulatory activities. Recepta will have rights to commercialize in Brazil, while Mersana will have rights to commercialize in the rest of the world. Mersana will be eligible to receive royalties from Recepta on sales in Brazil.
Pioneering R&D
“This licensing deal with Mersana follows pioneering R&D conducted by Recepta with this specific antibody, which was discovered by Ludwig Cancer Research, our partner and a global nonprofit research organization. It will enable the development of a novel immunoconjugate that has the potential to improve patient outcomes in oncology,” noted José Fernando Perez, PhD, Chief Executive Officer of Recepta.
“We are excited to develop a Fleximer-based immunoconjugate with this antibody to address unmet needs in cancer,” explained Anna Protopapas, President and Chief Executive Officer of Mersana. “This will expand our pipeline of oncology therapies that address the limitations of currently available antibody-drug conjugates and complement our objective to pursue one IND each year, starting with XMT-1522, our first product candidate with the potential to address significant unmet needs and improve patient outcomes in multiple oncology indications, later this year.”
XMT-1522 is an anti-HER2 antibody-drug conjugate using a novel, human anti-HER2 antibody optimized for cytotoxic payload delivery. Each antibody is conjugated to ~15 proprietary auristatin molecules using Mersana’s Fleximer technology.[1]
Last editorial review: July 14, 2015
Feature Image: Test tubes closeup – medical glassware. Photo courtesey: ©Fotolia 2015.
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