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On December 27, 2022, Gilead announced a partnership with Jounce
Therapeutics amended its license agreement for GS-1811 (formerly known as JTX-1811) to buy out GS-1811 for $67 million, and Gilead will be solely responsible for all research, development and commercialization of GS-1811 worldwide, with full R&D and commercial rights
.
GS-1811 is a CCR8-targeting antibody designed to selectively deplete immunosuppressive tumor-infiltrating T regulatory cells
in the tumor microenvironment.
GS-1811 is currently undergoing Phase 1 clinical trials to evaluate as a potential therapy for patients with solid tumors, with final primary outcome data
expected in 2024.
Jounce will no longer be entitled to potential milestone payments of up to $645 million in the original license agreement, as well as royalties
.
However, forgoing potential long-term benefits in exchange for this buyout funding for Jounce Corporation provides the company with sufficient cash to support the company's operations through the fourth quarter
of 2024.
Jounce CEO Richard
"This transaction allows us to extend our cash flow and remain focused on delivering meaningful and lasting benefits
to cancer patients," Murray said.
Given the challenges facing biotech companies in the capital markets, Jounce must strengthen its cash resources
at this time.
”
CCR8
CCR8CCR8 is a member of the chemokine receptor family and is a G protein-coupled receptor.
CCR8 is highly expressed in tumor-infiltrated Treg, lower in Treg cells of the thymus, spleen and peripheral blood, and lower in Th2 cells
.
There are four known receptors for CCR8: CCL1, CCL8, CCL16 and CCL18, of which the main receptor-chemokine CCL1 can recruit FOXp3+CCR8+Treg cells to infiltrate into tumor tissues and exercise immunosuppressive functions, while it can induce the upregulation of CCR8 expression on the surface of FOXp3+Treg cells, induce Ca2+ flow, and induce stat3-dependent upregulation of Foxp3, CD39, IL-10 and granzyme B expression.
This in turn enhances the immunosuppressive activity
of these tumor-infiltrating Treg cells.
Therefore, drugs targeting CCR8 can enhance anti-tumor immunity
by depleting tumor-infiltrating FOXp3+CCR8+Treg cells, or blocking the CCL1/CCR8 pathway.
Based on the plasticity of CCR8, it has shown good potential
in monoclonal antibodies, bispecific antibodies, and combination drugs.
At present, there are no CCR8-targeted drugs on the market in the world, and there are not many pipelines under development, all of which are before
clinical phase 2.
Domestic Emmefi small molecules are thriving, and Lixin Pharmaceutical's CCR8 monoclonal antibody has begun to lead
.
In terms of the development progress of the CCR8 project, the gap between home and abroad has not yet reached the extent that it cannot be crossed, and local enterprises are expected to catch up, looking forward to more positive news
in the future.
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