Collaboration will leverage GEMS platform to identify orally available drugs that target post-transcriptional control.

AstraZeneca and PTC Therapeutics will collaborate on the development of new therapies based on the latter’s GEMS™ (Gene Expression Modulation by Small-Molecules) platform. The partnership will initially focus on cancer but can cover up to eight targets across different therapeutic areas. AstraZeneca will pay PTC an up-front fee for initiation of the first target program, and provide the firm with committed research funding. PTC will also be eligible for research, development, regulatory, and commercial milestones. AstraZeneca retains global commercialization rights to resulting products, while PTC retains an option to participate in the development of selected candidates.

“PTC’s RNA biology expertise and the uniqueness of the GEMS technology are complementary to our internal efforts,” remarks Susan Galbraith, Ph.D., vp and head of the oncology innovative medicines research unit at AstraZeneca. “We believe that the GEMS technology will enable AstraZeneca to address important disease mechanisms that were intractable with our existing approaches.”

PTC is focused on the discovery, development, and commercialization of orally administered small molecule drugs that target post-transcriptional control processes. Compounds identified using the GEMS screening technology modulate gene expression by targeting the post-transcriptional control processes that act through the UTRs of mRNA molecules.

PTC claims the GEMS platform offers a number of advantages over traditional drug discovery approaches. These include the ability to address previously intractable targets, as well as identify alternative mechanisms for existing validated targets. GEMS also allows the identification of small molecules capable of up- or downregulating protein levels, and can address targets with unknown functions, PTC claims.

The firm’s lead clinical-stage candidate ataluren (PTC124®) is designed to enable the formation of a functioning protein in patients with genetic disorders due to a nonsense mutation. The drug is currently undergoing a long-term Phase III study in patients with nonsense-mutation cystic fibrosis (nmCF), and is in Phase II trials in patients with nonsense-mutation hemophilia A & B (nmHA/B) and nonsense-mutation methylmalonic acidemia (nmMMA). PTC has teamed up with Genzyme to develop and commercialize ataluren. Under terms of the deal PTC will commercialize ataluren in the U.S. and Canada, with Genzyme retaining commercialization rights to the drug in all other countries.  

PTC’s second clinical-stage oncology candidate, PTC299, is an orally administered, small molecule drug designed to inhibit the production of VEGF by targeting the post-transcriptional processes that regulate VEGF synthesis. PTC299 is currently undergoing a Phase Ib trial in patients with solid tumors, Phase Ib/II studies in women with metastatic breast cancer and in patients with human-immunodeficiency (HIV)-related Kaposi sarcoma, and a Phase II trial in neurofibromatosis type 2.

The firm’s early-stage pipeline includes an HCV program focused on inhibiting HCV replication. The program was partnered with Schering-Plough (now part of Merck & Co.) back in 2006, and has led to the selection of an orally available candidate that is currently in preclinical development. 

PTC has discovery-stage programs in multiple fields including antibacterials, oncology and musculoskeletal disorders, and ongoing collaborations with a number of nonprofit and commercial organizations, including Celgene, Gilead, the Muscular Dystrophy Association, Pfizer, Roche, and the Spinal Muscular Atrophy Association, and Parent Project Muscular Dystrophy.

In February the firm announced it had identified a chemical series of molecules that penetrates the blood-brain barrier in animal models and reduces levels of BMI1, a protein linked to drug-resistant cancers. The achievement represented a milestone in the firm’s collaboration with the Wellcome Trust, triggering a $2.2 million payment. Initiated in June 2010, the $5.4 million collaboration with the Wellcome Trust aims to develop BMI1-targeting drugs for the treatment of chemotherapy-resistant cancers.

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