Ubiquitous ubiquitins?

According to the National Center for Biotechnology Information, “Ubiquitin-specific proteases are deubiquitinating enzymes involved in the removal of ubiquitin from specific protein substrates resulting in protein salvage from proteasome degradation, regulation of protein localization or activation. DNA alteration and overexpression in different cancer types, as well as involvement in many cancer-associated pathways, make ubiquitin-specific proteases attractive for the cancer drug discovery purposes.”

While ubiquitin-specific proteases are emerging as potential targets in cancer and other diseases, inhibitors of USPs have been difficult to identify, in spite of the efforts of pharmaceutical and biotech companies. According to Tim Harrison, vice president of drug discovery at Almac Discovery, “Ubiquitin-specific proteases have been shown to play an important role in a number of key oncogenic pathways, and the identification of potent, selective inhibitors provides an exciting opportunity to fully exploit this novel biology, as well as further demonstrating the chemical tractability of this important target class.”

Under the terms of the agreement, Almac Discovery will receive an upfront payment of $14.5 million and be eligible to receive up to $349 million in payments based on achievement of certain predetermined milestones, as well as escalating tiered royalties on potential commercial sales of multiple products to the target by Genentech.

Almac Discovery’s novel, potent and selective small-molecule inhibitors will be the starting point for a two-year joint research program funded by Genentech, which will be responsible for all preclinical and clinical development, as well as commercialization of products coming out of the collaboration. The partnership is designed to translate Almac Discovery’s medicinal chemistry and biology into the clinic.

According to James Sabry, senior vice president and global head of Genentech Partnering, “We’re pleased to initiate this collaboration with Almac Discovery, where we hope to discover and develop therapies targeting an important USP that can potentially advance the standard of care for patients with cancer.”

The Almac Group, which provides a full range of contract services from biomarker and discovery services to active pharmaceutical ingredient development and manufacturing—as well as pharmaceutical development, clinical trial material supply and commercial-scale drug substance and drug product manufacturing—also recently announced an agreement with OncoMed Pharmaceuticals Inc. to develop a companion diagnostic test to help predict a patient’s likelihood of responding to OncoMed’s novel therapeutic that targets R-Spondin 3 (RSPO3). Anti-RSPO3 (OMP-13R10) has demonstrated activity in preclinical models against a variety of major tumor types, including colon, lung and ovarian cancers. Almac and OncoMed are currently developing a gene-expression RSPO3 CLIA assay that can be used to prospectively select patients in the clinical development of anti-RSPO3.

In addition, in July the Almac Group announced an expanded Asia Pacific presence with a new regional headquarters and clinical trial supply facility in Singapore. “Asia Pacific is a vital region for us, as currently 23 percent of global clinical trials for new pharmaceutical products are being conducted here. By basing our regional headquarters and operations in Singapore, we are better equipped to support our Asia-based clients in their own time zone and languages,” said Dr. Robert Dunlop, president and managing director of Almac’s Clinical Services business unit. “With the opening of our new Singapore facility, we are directly supporting studies run by regional and global pharmaceutical firms by providing critical manufacturing, packaging, supply chain management and interactive response technology support services in Asia Pacific.”