AstraZeneca is recruiting RNAi specialist Silence Therapeutics to develop treatments for cardiovascular, renal, metabolic, and respiratory diseases.
RNA interference, or RNAi, is a relatively new field of medicine in which therapeutic small interfering (si)RNA molecules — known as siRNA molecules — can selectively block genes and thus inhibit the production of disease-causing proteins.
John Strafford, Vice President and Head of Business Development at Silence Therapeutics, told me that “siRNA medicines have several unique properties.” These advantages include their patient-friendly nature due to the fact that a single subcutaneous injection can treat a patient for a month or longer, and their good safety profile as a result of strong specificity to the target tissue.
In collaboration with AstraZeneca, Silence will apply its established siRNA technology, which it is already using to treat liver disease, as well as other conditions in the heart, kidney and lung.
Although the specific therapeutic indications are currently undisclosed, AstraZeneca has an interest in conditions such as cardiovascular disease, nonalcoholic steatohepatitis (NASH), and chronic kidney disease, which could all be potential targets.
During the partnership, Silence will take responsibility for designing siRNA molecules against the gene targets selected by AstraZeneca, for manufacturing of material to support toxicology studies, and for phase I studies. AstraZeneca will then lead the clinical development and commercialization.
Silence anticipates starting work on five targets over the first three years of the collaboration and expects to have the first candidate drug nominated in 2022. In return, Silence will receive from AstraZeneca an upfront payment of €54M, an equity investment of €18M, and up to €364M in milestone payments per target. After the first stage, AstraZeneca will have the option to extend the deal to a further five targets.
Following the first candidate drug nomination, AstraZeneca will conduct Investigational New Drug enabling studies ahead of the first clinical trial. “We would typically expect such studies to take one to two years so the first phase I trial could feasibly begin in or around 2024,” Strafford told me.
As well as the collaboration with AstraZeneca, Silence Therapeutics is working with pharma companies Mallinckrodt and Takeda, and has its own internal pipeline. This includes an siRNA molecule targeting a protein called Lipoprotein(a) for cardiovascular disease, and another for treating beta thalassemia and myelodysplastic syndrome, which will both be tested in phase I clinical trials this year.
Though the RNAi field is still emerging, some of its first drugs have reached the market in the last few years. Earlier this month, for example, one of the leading companies in the field, Alnylam, had its second RNAi drug approved by the EMA.
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