Rapamycin inhibiting protein kinase mTORC1
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Astellas Pharma and PeptiDream today announced a research collaboration and license agreement to discover novel protein degraders for two targets selected by Astellas. Under the agreement between the two companies, Astellas will have the option to select up to three additional targets to be included in the collaboration.

Astellas will provide PeptiDream with an upfront payment of $21M (¥3.0 billion). The biotech is eligible to receive discovery, development and commercial sales milestones of up to $150M (¥20.6 billion) per target. PeptiDream is also eligible to receive single-digit percent royalty payments on net sales of any products arising from the collaboration.

The companies plan to combine PeptiDream’s PDPS (Peptide Discovery Platform System) technology with Astellas’ drug discovery capabilities to discover multiple next-generation protein degraders targeting diverse targets that go beyond existing technologies. Astellas will be responsible for the development and commercialization of products created.

“This transaction further validates the potential of our PDPS technology to obtain highly selective peptides, which enables creative approaches in the area of targeted protein degraders. We believe that through this research collaboration, we can leverage the strengths of both companies to advance the development of innovative drugs,” says Keiichi Masuya, chief operating officer, PeptiDream.

The PDPS platform aims to generate highly diverse peptide libraries and efficiently identify macrocyclic peptides with high affinity and selectivity for a given target from the library. PeptiDream’s pipeline includes candidates targeting PD-L1, CD38, S2-protein, GhR, Glypican-3, myostatin, TfR, c-Kit, and c-Met. These are partnered with companies that include Bristol Myers Squibb, Novartis, Takeda, and Genentech.

Astellas says it focuses on targeted protein degraders directed to undruggable targets that are difficult to approach with conventional technologies. The big pharma has established a Focus Area Approach for its research and development strategy.

“Targeted Protein Degradation is one of the Primary Focuses of Astellas. We hope this collaboration will bring synergies between the two companies’ cutting-edge research and will ultimately lead to the expansion of Astellas’ portfolio and development of new therapeutics for patients with significant unmet medical needs,” said Adam Pearson, Chief Strategy Officer, Astellas.

The goal is to hit so-far undruggable targets. Conventional small-molecule and antibody drugs can access only about 20 percent of the proteins. Protein degraders have been developed to target undruggable targets and overcome drug resistance through ubiquitin–proteasome pathway and lysosome pathway. Recently, proteolysis-targeting chimeras (PROTACs) have aroused great interest in drug discovery, and some of them are now in clinical trials.

Founded in 2006, PeptiDream says its PDPS technology enables the production of highly diverse non-standard peptide libraries with high efficiency, for the identification of potent and selective macrocyclic peptide candidates. These can then be developed into peptide-based, small molecule-based, or peptide-drug conjugate (PDC) and multi-functional peptide conjugates (MPC)-based therapeutics and diagnostics.

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