This expansion includes up to three additional targets focused on host factors for SARS-CoV-2, including ACE2 and TMPRSS2, both of which are considered critical for viral entry, with the potential for an additional host target to emerge from Vir’s functional genomics work.
Pursuant to an amendment to the collaboration agreement, the companies will utilize Alnylam’s recent advances in lung delivery of novel conjugates of siRNA – the molecules that mediate RNAi – together with Vir’s infectious disease expertise and established capabilities, to bring forward up to three additional host factor-targeting development candidates (DCs) to treat SARS-CoV-2 and potentially other coronaviruses as well. The two named targets include angiotensin converting enzyme-2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2). ACE2 is known to be the viral entry receptor for SARS-CoV-2 and other coronaviruses, while TMPRSS2 is believed to cleave the SARS-CoV-2 spike protein to facilitate cellular attachment. The third target is expected to emerge from Vir’s ongoing functional genomics efforts to identify novel host factors pertinent to coronaviral infection and targetable by siRNA, mAbs or small molecules.
As part of the original collaboration to advance investigational RNAi therapeutics to treat disease caused by coronavirus infection, Alnylam has designed and synthesized over 350 siRNAs targeting highly conserved regions of the SARS-CoV-2 genome. Lead siRNAs have recently been identified by scientists at Alnylam and are now being further evaluated by scientists at Vir for anti-viral activity in support of DC selection. Upon DC selection, Vir will lead development efforts – working closely with Alnylam to generate the data required to enable the potential for rapid commencement of clinical studies.
“Vir is aggressively pursuing multiple platforms and multiple therapeutic strategies to combat the COVID-19 pandemic. We are excited about our partnership with Alnylam – which has already led to identification of promising siRNAs targeting SARS-CoV-2 – and we’re pleased to now expand our efforts to evaluate the anti-viral effects of siRNAs targeting human host factors,” said George Scangos, Ph.D., CEO of Vir. “We share a sense of urgency with Alnylam in advancing these efforts as quickly as possible and with the highest priority.”
“The biopharmaceutical industry needs to advance its full armamentarium of potential treatment approaches and strategies to address the COVID-19 pandemic. To this end, we are excited about the promise of targeting host factors critical for viral infection and replication, in addition to our efforts directly targeting the SARS-CoV-2 genome,” said John Maraganore, Ph.D., Chief Executive Officer of Alnylam Pharmaceuticals. “At this time of enormous public health need, we plan to act with the utmost urgency to broaden and accelerate our efforts with Vir to develop investigational RNAi therapeutics against COVID-19, and potentially future coronavirus diseases.”
Under the collaboration and license agreement, as amended, in addition to leading development of selected DCs, Vir will lead commercialization of any products emerging from the collaboration that gain regulatory approval. At clinical proof of concept, Alnylam will have an option to share equally in any profits and losses associated with the development and commercialization of each coronavirus program. Alternatively, Alnylam may elect to earn development and commercialization milestones and royalties on net sales of any products resulting from the collaboration in amounts agreed upon for each coronavirus program. These additional targets expand the companies’ collaboration and license agreement announced in 2017, and the subsequent amendment to that agreement announced in March 2020, to now develop novel siRNAs for up to nine infectious disease targets in total, including hepatitis B virus in the Vir-2218 (ALN-HBV02) program currently in Phase 1/2 studies.