Being flexible with Fleximer

Mersana, Endo collaborate on antibody-drug conjugate development

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CAMBRIDGE, Mass.—A new collaboration was announced in earlyMarch between Mersana Therapeutics Inc. and Chadds Ford, Pa.-based EndoPharmaceuticals for the development of next-generation antibody-drug conjugates(ADCs). Per the agreement, Endo will pay Mersana an upfront fee for the rightto use Mersana's Fleximer technology to develop novel ADC candidates against a singlecancer target.
"The collaboration with Mersana further enhances Endo'sDiscovery and Early Development portfolio and is validation of ourcollaborative R&D approach for drug discovery and development," IvanGergel, executive vice president of research and development and chiefscientific officer at Endo, said in a press release regarding the deal. "UsingMersana's Fleximer-ADC technology, we aim to develop more efficacious and safertreatment options to improve patient outcomes."
Under the terms of the agreement, Mersana will beresponsible for generating the ADCs using Endo's antibody and its ownconjugation technology. Endo will be responsible for providing novelantibodies, as well as product development, manufacturing and commercializationof any Fleximer-ADC products that result from the collaboration. The twocompanies can mutually agree to pursue an additional two targets over the nexttwo years, and if all three targets are pursued, Mersana stands to receive morethan $270 million in milestones, as well as royalties on worldwide net sales ofany ADC products that result.
Mersana's ADC technology is based on Fleximer, itsproprietary biodegradable polymer system, as well as a wide range of novellinkers that make it possible to attach a variety of antitumor payloads. OnceFleximer 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. Thenovel linker systems are stable in the blood stream and trigger payload releaseonce they are inside the targeted cancer cells.
"There's a number of features that really make ourtechnology next-generation, but I think the two most prominent ones are that wecan load much more drug and a variety of different drugs with differentmechanisms of action. We're not limited just to the antitubulins that one seescurrently being used for antibody-drug conjugates," says Timothy Lowinger,chief scientific officer at Mersana. "We can use many different types ofanticancer drugs effectively. The other key differentiator is because theFleximer technology can simultaneously improve the pharmacokinetics of smallproteins, we don't need to use a full-size antibody; we can use an antibodyfragment as the targeting group to deliver the drug payload, and the realadvantage there is that you can control the size and have the potential formuch better solid tumor penetration than you do with a full-size antibody."
The collaboration was the result of mutual interest andinterlocking goals on the part of the two companies, says Michael Metzger,executive vice president and chief operating officer at Mersana. The dealoffers Mersana the chance to further develop its technology, and the milestonepayments will allow for additional investments into its platform and programs,he notes, adding that the company also hopes to build a pipeline with itstechnology. The collaboration represents "an important deal for us," he says.
"[Endo] had a technology and know-how and desire, they'rebuilding an oncology franchise and they had an interest in getting intoantibody-drug conjugates, and so they were attracted to our technologycapabilities," says Metzger. "And we were starting to emerge, I think, as a newantibody-drug conjugate company with aspirations to partner with leadingcompanies, and we were attracted to them in that regard. It was sort a meetingof the minds relative to their capabilities and our capabilities."
Metzger expects that in terms of the growth and popularityof ADCs in the market, "the ability to express antigens and approach them withantibody-drug conjugates will allow for additional, larger tumors potentiallyto 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 potentialof this approach," Lowinger agrees, pointing to the response rates being seenfrom existing ADCs such as Genentech's TDM1. "Clinicians are seeing 60- to70-percent response rates where the tumors are shrinking, not just adding a fewmonths of survival but really making a dramatic difference in these veryhard-to-treat patients. We think that's why the industry as a whole is gettingmore and more focused on ADCs and the potential that they offer."

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