Being flexible with Fleximer
CAMBRIDGE, Mass.—A new collaboration was announced in early March between Mersana Therapeutics Inc. and Chadds Ford, Pa.-based Endo Pharmaceuticals for the development of next-generation antibody-drug conjugates (ADCs). Per the agreement, Endo will pay Mersana an upfront fee for the right to use Mersana's Fleximer technology to develop novel ADC candidates against a single cancer target.
"The collaboration with Mersana further enhances Endo's Discovery and Early Development portfolio and is validation of our collaborative R&D approach for drug discovery and development," Ivan Gergel, executive vice president of research and development and chief scientific officer at Endo, said in a press release regarding the deal. "Using Mersana 's Fleximer-ADC technology, we aim to develop more efficacious and safer treatment options to improve patient outcomes."
Under the terms of the agreement, Mersana will be responsible for generating the ADCs using Endo's antibody and its own conjugation technology. Endo will be responsible for providing novel antibodies, as well as product development, manufacturing and commercialization of any Fleximer-ADC products that result from the collaboration. The two companies can mutually agree to pursue an additional two targets over the next two years, and if all three targets are pursued, Mersana stands to receive more than $270 million in milestones, as well as royalties on worldwide net sales of any ADC products that result.
Mersana's ADC technology is based on Fleximer, its proprietary biodegradable polymer system, as well as a wide range of novel linkers that make it possible to attach a variety of antitumor payloads. Once Fleximer is loaded with the drug of choice, it is attached via a different, highly stable linker to an antibody or antibody fragment to create an ADC. The novel linker systems are stable in the blood stream and trigger payload release once they are inside the targeted cancer cells.
"There's a number of features that really make our technology next-generation, but I think the two most prominent ones are that we can load much more drug and a variety of different drugs with different mechanisms of action. We're not limited just to the antitubulins that one sees currently being used for antibody-drug conjugates," says Timothy Lowinger, chief scientific officer at Mersana. "We can use many different types of anticancer drugs effectively. The other key differentiator is because the Fleximer technology can simultaneously improve the pharmacokinetics of small proteins, we don't need to use a full-size antibody; we can use an antibody fragment as the targeting group to deliver the drug payload, and the real advantage there is that you can control the size and have the potential for much better solid tumor penetration than you do with a full-size antibody."
The collaboration was the result of mutual interest and interlocking goals on the part of the two companies, says Michael Metzger, executive vice president and chief operating officer at Mersana. The deal offers Mersana the chance to further develop its technology, and the milestone payments will allow for additional investments into its platform and programs, he notes, adding that the company also hopes to build a pipeline with its technology. The collaboration represents "an important deal for us," he says.
"[Endo] had a technology and know-how and desire, they're building an oncology franchise and they had an interest in getting into antibody-drug conjugates, and so they were attracted to our technology capabilities," says Metzger. "And we were starting to emerge, I think, as a new antibody-drug conjugate company with aspirations to partner with leading companies, and we were attracted to them in that regard. It was sort a meeting of the minds relative to their capabilities and our capabilities."
Metzger expects that in terms of the growth and popularity of ADCs in the market, "the ability to express antigens and approach them with antibody-drug conjugates will allow for additional, larger tumors potentially to be treated," adding that he believes "we're just scratching the surface now, at least developmentally."
"I think that there's tremendous interest in the potential of this approach," Lowinger agrees, pointing to the response rates being seen from existing ADCs such as Genentech's TDM1. "Clinicians are seeing 60- to 70-percent response rates where the tumors are shrinking, not just adding a few months of survival but really making a dramatic difference in these very hard-to- treat patients. We think that's why the industry as a whole is getting more and more focused on ADCs and the potential that they offer."