Mersana Therapeutics and GSK have confirmed that the companies have entered into a global collaboration that provides GSK an exclusive option to co-develop and commercialize XMT-2056, an Immunosynthen antibody-drug conjugate (ADC) that targets a novel epitope of HER2.
XMT-2056 is designed to activate the innate immune system through STING signaling in both tumor-resident immune cells and in tumor cells.
In developing XMT-2056, drug developers found that by leveraging an ADC strategy, systemic administration of a STING agonist with tumor-targeted delivery can be achieved, potentially overcoming limitations of either intratumoral or intravenous administrations of unconjugated, small molecule STING agonists.
The investigational agent was generated through conjugation of Immunosynthen, a platform that employs a novel STING agonist payload specifically designed for ADCs, to HT-19, a HER2-targeting antibody that binds to a novel epitope and does not compete for binding with either trastuzumab (Herceptin®; Genentech/Roche) or pertuzumab (Perjeta®; Genentech/Roche).
“GSK brings highly complementary development and commercial capabilities, a wealth of immuno-oncology experience, a deep knowledge of the STING pathway, and a shared vision for XMT-2056’s broad potential,” noted Anna Protopapas, President and Chief Executive Officer of Mersana Therapeutics.
“We believe this agreement solidifies Mersana’s position as a partner of choice during this momentous period in the ADC space and serves as validation for our Immunosynthen platform, which takes ADCs beyond the cytotoxic realm by enabling a targeted stimulation of the innate immune system. Additionally, the agreement structure demonstrates our ability to generate meaningful non-dilutive capital upfront to support the development of our innovative candidates while also providing the potential for meaningful downstream economics,” Protopapas added.
In preclinical models, XMT-2056 demonstrated robust anti-tumor activity as a monotherapy in both HER2-high and HER2-low expressing models, and enhanced efficacy has been shown when used in combination with multiple approved agents, including trastuzumab, pertuzumab, anti-PD-1, or trastuzumab deruxtecan (Enhertu®; Daiichi Sankyo and AstraZeneca).
The initial results of these preclinical studies demonstrated that XMT-2056 has target-dependent anti-tumor activity in vivo and is well tolerated in non-human primates at significantly higher exposure levels than those required for anti-tumor activity.
Preclinical data also suggest that XMT-2056 has the potential to enable immunological memory for prolonged anti-tumor activity.
Phase 1 trial
Mersana expects to initiate a Phase 1 clinical trial of XMT-2056 to investigate its potential in a range of HER2-expressing tumors such as breast, gastric and non-small-cell lung cancers. The U.S. Food and Drug Administration recently granted an orphan drug designation to XMT-2056 for the treatment of gastric cancer.
“At GSK, our goal is to bring transformational treatment options to patients with cancer, so we are pleased to be able to enter into this agreement for XMT-2056,” said John Lepore, Senior Vice President of Research, at GSK.
“Its preclinical data demonstrate how it might work to harness the immune system by activating the STING pathway, and its differentiated mechanism of action offers the potential for additional clinical benefit in patients with HER2-expressing tumors,” Lepore added.
Under the terms of the agreement, Mersana will receive an upfront option purchase fee of $100 million. Mersana also is eligible to receive up to $1.36 billion in the form of an option exercise payment and development, regulatory and commercial milestone payments if GSK exercises its option.
Mersana has retained options to profit-share and to co-promote in the United States. If it exercises its profit-share option, Mersana will be eligible to receive tiered royalties on net sales outside of the United States. If Mersana does not elect to profit-share, it is eligible to receive double-digit tiered royalties on global net sales.
If GSK opts into the license, the effectiveness of the license grant may be subject to customary closing conditions, including review under the Hart-Scott-Rodino Act.
Highlights of prescribing information
Trastuzumab (Herceptin®; Genentech/Roche)[Prescribing Information]
Pertuzumab (Perjeta®; Genentech/Roche)[Prescribing Information]
Trastuzumab deruxtecan (Enhertu®; Daiichi Sankyo and AstraZeneca)[Prescribing Information]
 Duvall JR, Bukhalid RA, Cetinbas NM, Catcott KC, Lancaster K, Bentley KW, Clark S, Clardy S, Collins SD, et al. XMT-2056, a HER2-targeted Immunosynthen STING-agonist antibody-drug conjugate, binds a novel epitope of HER2 and shows increased anti-tumor activity in combination with trastuzumab and pertuzumab (Abstract 3503 / 5).
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