May 2018

09 May Nonclinical Safety Evaluation of GalNAc-siRNA Conjugates

We presented a nonclinical safety evaluation of GalNAc-siRNA conjugates at the 8th Annual Biologics Symposium, being held May 8-9, 2018 in Plainsboro, NJ. View the presentation

08 May New Preclinical Data Demonstrating CNS Delivery of RNAi Therapeutics

We presented initial data demonstrating delivery of nove small interfering RNA (siRNA) conjugates to the central nervous system (CNS) at the TIDES: Oligonucleotides and Peptide Therapeutics 2018 Annual Meeting, being held May 7-10, 2018 in Boston, MA. Read our press release View the presentation

24 Apr New Positive Clinical Results for Patisiran at AAN

We presented new positive results from the APOLLO Phase 3 study of patisiran, an investigational RNAi therapeutic for the treatment of hereditary ATTR (hATTR) amyloidosis, at the American Academy of Neurology (AAN) 2018 Annual Meeting, being held April 21-27, 2018 in Los Angeles. Read our press release Adams et al. – “Patisiran, an Investigational RNAi Therapeutic for Patients with Hereditary Transthyretin-Mediated (hATTR) Amyloidosis: Results from the Phase 3 APOLLO Study” Adams et al. – “Evaluation of Quality of Life and Disability in Patients with Hereditary Transthyretin-Mediated (hATTR) Amyloidosis with Polyneuropathy Following Treatment with Patisiran, an Investigational RNAi Therapeutic: Results from the Phase 3 APOLLO Study” Mora et al. – “Utility of Genetic Testing to Identify Individuals Suspected of Having Hereditary ATTR (hATTR) Amyloidosis”

14 Apr New Positive Clinical Results for Givosiran at EASL

We presented new positive results from the Phase 1, Phase 1/2, and EXPLORE natural history studies of givosiran, an investigational RNAi therapeutic targeting aminolevulinic acid synthase 1 (ALAS1) for the treatment of acute hepatic porphyrias (AHPs), at the European Association for the Study of the Liver (EASL) 53^rd Annual International Liver Congress, being held April 11-15, 2018 in Paris, France. Read our press release Sardh et al. - "Phase 1/2, Randomized, Placebo Controlled and Open Label Extension Studies of Givosiran, an Investigational RNA Interference (RNAi) Therapeutic, in Patients with Acute Intermittent Porphyria" Gouya et al. - "EXPLORE: A Prospective, Multinational, Natural History Study of Patients with Acute Hepatic Porphyrias (AHPs) with Recurrent Attacks"

28 Mar New Clinical Results from APOLLO Phase 3 Study of Patisiran at ISA

We presented additional results from the APOLLO Phase 3 study of patisiran, an investigational RNAi therapeutic for the treatment of hereditary ATTR (hATTR) amyloidosis, at the 16th International Symposium on Amyloidosis (ISA), held March 26-29, 2018 in Kumamoto, Japan. Read our press release Kristen et al. –...

19 Feb Nonclinical research published in Nature Communications describing optimization of GalNAc-siRNA conjugates to minimize off-target potential and maximize therapeutic index

During initial development candidate selection, a subset of chemically-modified siRNAs conjugated to trivalent GalNAc does not pass the stringent safety criteria for nonclinical evaluation due to rat hepatotoxicity. This body of work provides evidence that the observed hepatotoxicity is largely attributed to unintended base-pairing of the seed region of the siRNA antisense strand with off-target mRNAs, with little or no contribution from chemical modifications or the perturbation of RNAi pathways. Changing the sequence of the seed region or introducing thermally destabilizing modifications, such as glycol nucleic acid (GNA), in that region mitigated hepatotoxicity. Introduction of seed GNA has the potential to minimize the occurrence of hepatotoxic siRNAs across species without compromising on-target activity. This approach, among others, provides the opportunity to expand the number of initial candidates for nonclinical testing and to streamline the process of development candidate selection for RNAi therapeutics. Read article in Nature Communications