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Sacituzumab govitecan shows promise in treating the most aggressive type of breast cancer

Sotio

30/12/2021 | 3 minutes to read

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A unique ADC, which delivers a high dose of a cancer-killing drug to tumor cells through a targeted antibody, has been found in a global phase 3 clinical study to nearly double the survival time of patients with refractory metastatic triple-negative breast cancer. The study of the ADC drug sacituzumabgovitecan (SG), reported superior outcomes compared to single-agent chemotherapy, the standard for treating metastatic triple-negative breast cancer. The phase 3 results of the study, known as ASCENT, were published in the New England Journal of Medicine. SG, which was developed and is manufactured by Immunomedics, a subsidiary of Gilead Sciences, received accelerated approval by the U.S. Food and Drug Administration in April 2020 on the basis of favorable phase 1/2 clinical trials, with full approval contingent on the confirmatory phase 3 results. ASCENT is a global study to evaluate the safety and efficacy of the antibody drug conjugate compared to chemotherapy in 529 patients with metastatic triple-negative breast cancer whose cancer had relapsed or was resistant to at least two other forms of therapy. The investigators found that median progression-free survival with the ADC agent was 5.6 months compared to 1.7 months with chemotherapy, and that median overall survival was 12.1 months with the ADC agent compared to 6.7 months with chemotherapy. The study also found that the response rate – that is, shrinkage in the size of the metastatic tumor sites – was 35% after administration of ADC compared to 5% with chemotherapy.

CLINICAL

No clear response ends early-stage Daiichi Sankyo ADC program

Daiichi took DS-6157 into the clinic in light of the unmet need in GIST and evidence that GPR20 is selectively and abundantly expressed in the indication. While the function of GPR20 in GIST is unknown, Daiichi hypothesized that over-expression of the G protein-coupled receptor makes it an attractive target for an ADC, offering it a way to get a payload to cancer cells without harming healthy tissues and thereby address the need for a new mechanism of action in GIST. That hypothesis fell at the first clinical hurdle. Daiichi is yet to share data from the study but used its second-quarter results to reveal it saw “no clear responses” at any of the six dose levels tested in the phase 1 trial. The lack of activity led Daiichi to scrap DS-6157 development without moving into the dose-expansion portion of the study.

Seagenbets its newly acquired HER2-ADC disitamabvedotin can challenge Enhertu

Talking about the competitor product, Enhertu, Seagen CEO Clay Siegall said the molecule internalizes, but it’s kind of a middle of the road internalization. The antibody used in RC48, which is what we licensed from RemeGen, was selected based on incredibly rapid internalization.But both Enhertu and Kadcyla are cut from the same cloth, as they use Herceptin as their antibody. Meanwhile, the antibody component for Seagen’s new drug, disitamab, is a novel medicine. Compared to Enhertu and Kadcyla, disitamabvedotin has superior tumor-binding ability and tumor uptake, Seagen says. That’s what was attractive to Seagen, which has established itself as perhaps the premier developer of ADCs thanks largely to its payload-linker technology.

DEALS AND FINANCING

Expanded cancer ADC deal between Synaffix and Mersana could be worth $1B

Synaffix announced the expansion of its license agreement with Mersana.Mersana will expand its access to Synaffix'sGlycoConnect site-specific ADC bioconjugation technology for six additional ADC targets. The license rights granted to Mersana are tied to specific ADC targets to be selected and provide non-exclusive access to deploy GlycoConnect site-specific ADC bioconjugation technology against the specified targets. Under the expanded deal, Synaffix is eligible to receive upfront and milestone payments on a per-target basis with a total potential deal value exceeding $1 billion plus royalties. This builds on the long-term relationship between the two companies announced in 2019.

LegoChem announced deals with Sotio Biotech and Antengene on its ConjuAll ADC technology.

SOTIO Biotech licensedLegoChem Biosciences technology for five new ADC programs.LegoChem and Antengenewill jointly generate and evaluate ADC candidates using Antengene's antibodies and LCB's next generation ADC technology platform.

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