Daiichi Sankyo launches its STING operation against cancer

The development of STING agonists for cancer has been beset by safety issues and discontinued programmes, but Daiichi Sankyo is hoping a new antibody-drug conjugate (ADC) could succeed where others have failed.

The Japanese group has started dosing patients in a phase 1 trial of the ADC, codenamed DS3610, in patients with advanced, metastatic or unresectable solid tumours for which no additional standard therapy is available. It is expected to enrol around 70 subjects at sites in Asia, Europe and North America.

STING (stimulator of interferon genes) emerged as a hot new target in oncology a few years ago, with several companies rushing to develop drugs that activate the protein and – in theory at least – boost innate immune responses against cancer cells in the tumour microenvironment.

MSD (known as Merck & Co in the US and Canada) took an early lead with its ulevostinag (MK-1454) candidate, but shelved it in 2021 after it failed to impress in studies as a monotherapy and in combination with MS's PD-1 inhibitor Keytruda (pembrolizumab).

Another drug from Novartis/Aduro (ADU-S100) was abandoned in 2019 after generating weak clinical results, and other casualties have been recorded in STING agonist programmes pursued by Pfizer, Takeda, Mersana, Codiak, Mersana, and others.

There is still plenty of interest in STING as a target, however, with Boehringer Ingelheim, Bristol Myers Squibb, GSK, and Takeda among the companies that list active programmes in their pipeline, mostly in early-stage development.

According to Daiichi Sankyo, DS3610 consists of a monoclonal antibody with novel modifications to the Fc part of its structure – the cellular target hasn't been revealed – and carries a STING agonist as a payload.

"By combining precise tumour targeting with an immunotherapy payload, Daiichi Sankyo is exploring a new way to harness the body's own defences to attack cancer," said Ken Takeshita, the Japanese company's R&D head.

"The initiation of this first-in-human trial of DS3610 represents an important step forward in advancing the next wave of our antibody drug conjugate portfolio and reaffirms our commitment to creating transformative medicines for patients with cancer," he added.

The start of the trial takes the number of ADCs in clinical development by Daiichi Sankyo to seven, led by HER2-directed Enhertu (trastuzumab deruxtecan) and TROP2-targeting Datroway (datopotamab deruxtecan) – both already on the market and partnered with AstraZeneca.

Following after are candidates targeting B7-H3 (ifinatamab deruxtecan), CDH6 (raludotatug deruxtecan), and HER3 (patritumab deruxtecan), all partnered with MSD, and an in-house candidate, DS-3939, directed against TA-MUC1.

Photo by Andrey Tikhonovskiy on Unsplash