Mersana Therapeutics has signed a research collaboration and license agreement with Janssen Biotech, one of the Janssen Pharmaceutical Companies of Johnson & Johnson, to discover and develop novel antibody-drug conjugates (ADC) for three new targets for the treatment of cancers in areas of high unmet medical need. The agreement was facilitated by Johnson & Johnson Innovation.

Under the terms of the agreement, Janssen will provide proprietary antibodies for three targets while Mersana will apply its expertise to discover novel ADC product candidates.  Mersana will use its proprietary Dolasynthen platform, a homogeneous auristatin F hydroxypropyl amide ADC platform that was designed to increase the efficacy, safety, and tolerability of ADCs and help overcome the limitations of traditional ADCs in which drugs are directly conjugated to antibodies. In addition, Mersana may leverage Synaffix’s GlycoConnect™, a simple, yet powerful, platform technology enabling best-in-class ADCs, bispecific antibodies, and the targeted delivery of various therapeutic payloads, without modifying the antibody sequence, as its preferred site-specific ADC bioconjugation technology.

Mersana will collaborate with Janssen on target candidates during preclinical development, with Janssen being solely responsible for clinical development and commercialization.

Unfront payment and more
As part of the agreement, Mersana also will receive an upfront payment of US $ 40 million. The company is also eligible to receive reimbursement of certain costs as well as more than US $ 1 billion in potential milestone payments, plus mid-single-digit to low double-digit percentage royalties on worldwide net sales of ADCs against the selected targets.

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“We are very excited to enter into this collaboration with Janssen as we work to transform outcomes for patients,” noted Anna Protopapas, President and Chief Executive Officer of Mersana Therapeutics.

Anna Protopapas, President and Chief Executive Officer of Mersana Therapeutics.

“Our fully homogenous Dolasynthen platform enables both precise control of drug-to-antibody ratio (DAR) as well as the ability to vary the DAR across a broad range. Dolasynthen provides a unique opportunity to optimally design an ADC matched to a given target. We look forward to bringing both the differentiated capabilities of our Dolasynthen platform and our deep expertise in optimizing ADCs to this collaboration,” she added.

“In addition, by extending our platforms and expertise to new programs beyond our promising wholly-owned and first-in-class pipeline of ADC candidates, we see this value-driving collaboration as further strengthening our financial position as we seek to deliver important new treatments for patients living with cancer,” Protopapas concluded.

Ongoing development
Unrelated to this agreement, Mersana continues developing its lead product candidate, upifitamab rilsodotin (UpRi; previously known as XMT 1536), a Dolaflexin ADC targeting NaPi2b comprised of a unique humanized antibody conjugated with 10-15 auristatin F- hydroxypropylamide (AF-HPA) payload molecules. AF-HPA is a cell-permeable, antimitotic compound that is slowly metabolized intratumorally to an active, very low-permeable metabolite, auristatin F (AF), resulting in controlled bystander killing.

Upifitamab rilsodotin is being studied in a single-arm registration trial in patients with platinum-resistant ovarian cancer, as well as a multi-center Phase 1 open-label, umbrella study designed to establish the maximum tolerated dose (MTD) for the investigational ADC in combination with other therapeutic agents.[1][2]

Mersana company is also developing XMT-1592, an ADC targeting NaPi2b-expressing tumors, which was created using Mersana’s customizable and homogeneous Dolasynthen platform and is in the dose-escalation portion of a Phase 1 proof-of-concept clinical study.

Clinical trials
First-in-Human Study of XMT-1536 in Cancers Likely to Express NaPi2b – NCT03319628
Study of Upifitamab Rilsodotin in Combination With Other Agent(s) in Participants With High-grade Serous Ovarian Cancer (UPGRADE) – NCT04907968

[1] Yurkovetskiy AV, Bodyak ND, Yin M, Thomas JD, Clardy SM, Conlon PR, Stevenson CA, Uttard A, Qin L, Gumerov DR, Ter-Ovanesyan E, Bu C, Johnson AJ, Gurijala VR, McGillicuddy D, DeVit MJ, Poling LL, Protopopova M, Xu L, Zhang Q, Park PU, Bergstrom DA, Lowinger TB. Dolaflexin: A Novel Antibody-Drug Conjugate Platform Featuring High Drug Loading and a Controlled Bystander Effect. Mol Cancer Ther. 2021 May;20(5):885-895. doi: 10.1158/1535-7163.MCT-20-0166. Epub 2021 Mar 15. PMID: 33722857.
[2] Bodyak ND, Mosher R, Yurkovetskiy AV, Yin M, Bu C, Conlon PR, Demady DR, DeVit MJ, Gumerov DR, Gurijala VR, Lee W, McGillicuddy D, Park PU, Poling LL, Protopova M, Qin L, Stevenson CA, Ter-Ovanesyan E, Uttard A, Xiao D, Xu J, Xu L, Bergstrom DA, Lowinger TB. The Dolaflexin-based Antibody-Drug Conjugate XMT-1536 Targets the Solid Tumor Lineage Antigen SLC34A2/NaPi2b. Mol Cancer Ther. 2021 May;20(5):896-905. doi: 10.1158/1535-7163.MCT-20-0183. Epub 2021 Mar 15. PMID: 33722858.

Featured image: Mersana Laboratories. Photo courtesy: © 2016 – 2022 Mersana Therapeutics. Used with permission


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