SCY-635 / SCYNEXIS - LARVOL DELTA

Assessing Trans-Inhibition of OATP1B1 and OATP1B3 by Calcineurin and/or PPIase Inhibitors and Global Identification of OATP1B1/3-Associated Proteins. (PubMed, Pharmaceutics) - "Various drugs including the calcineurin inhibitor (CNI) cyclosporine A (CsA) exert preincubation-induced trans-inhibitory effects upon OATP1B1 and/or OATP1B3 (abbreviated as OATP1B1/3) by unknown mechanism(s). A total of 861 and 357 proteins were identified as specifically associated with OATP1B1 and OATP1B3, respectively, including various protein kinases, ubiquitin-related enzymes, the tacrolimus (FK506)-binding proteins FKBP5 and FKBP8, and several known regulatory targets of calcineurin. The current study reports several novel findings that expand our understanding of impaired OATP1B1/3 function; these include preincubation-induced trans-inhibition of OATP1B1/3 by the CNI tacrolimus, greater preincubation-induced inhibition by CsA compared to its non-CNI analogue SCY-635, and association of OATP1B1/3 with various proteins relevant to established and candidate OATP1B1/3 regulatory processes."

Journal • Targeted Protein Degradation • FKBP5

Quantifying antiviral activity optimizes drug combinations against hepatitis C virus infection. (PubMed) - Proc Natl Acad Sci U S A - "From the calculated IIP of 15 anti-HCV drugs from different classes [telaprevir, danoprevir, asunaprevir, simeprevir, sofosbuvir (SOF), VX-222, dasabuvir, nesbuvir, tegobuvir, daclatasvir, ledipasvir, IFN-α, IFN-λ1, cyclosporin A, and SCY-635], we found that the nucleoside polymerase inhibitor SOF had one of the largest potentials to inhibit viral replication events. Our quantification analysis clearly indicated an advantage of triple-DAA treatments over double-DAA treatments, with triple-DAA treatments showing enhanced antiviral activity and a significantly lower probability for drug resistance to emerge at clinically relevant drug concentrations. Our framework provides quantitative information to consider in designing multidrug strategies before costly clinical trials."

Journal • Biosimilar • Hepatitis C Virus • Immunology

Scynexis announces results from SCY-635 Phase 2a study on HCV (News Medical) - "Scynexis...announced that the results of a Phase 2a study of...SCY-635...will be the subject of an oral presentation at the 63rd Annual Meeting of the American Association for the Study of Liver Diseases..."

P2 data • Hepatitis C Virus

Short duration treatment with SCY-635 restores sensitivity to Peg-IFN/RBV in difficult to treat, IL28B TT/CT, HCV genotype 1 patients (AASLD 2012) - Presentation time: Nov 11, 2012; 5:15 AM - 5:30 PM; P2, N=10; SCY635-201; Addition of SCY-635 to Peg-IFN/RBV therapy resulted in improved antiviral activity at day 28 compared to Peg-IFN/RBV alone (change from baseline -2.49 vs. -1.23 log10 IU/mL, respectively)

P2 data • Hepatitis C Virus

Scynexis aims to raise $15M; hepatitis C drug candidate in phase 2 trials (MedCityNews) - Scynexis has raised $5M in a fundraising effort targeted to reach up to $15M; Scynexis’s SCY-635, the first drug candidate to emerge from the drug pipeline may serve as a potential replacement for recombinant interferon, the current standard hepatitis C; SCY-635 is currently in P2 clinical trials

Product update • Hepatitis C Virus

The non-immunosuppressive cyclophilin inhibitor SCY-635 exerts clinical anti-HCV activity by upregulating the expression of endogenous interferons (AASLD 2011) - Presentation time: Nov 07 8:00 AM - 5:30 PM; P=NA, N=NA; All subjects who received active treatment exhibited SCY-635-dependent increases in the plasma protein concentrations of interferons α, λ1, & λ3 with concordant increases in the plasma protein concentration of 2'5'OAS1 & neopterin; PBO subjects showed no consistent changes in interferon expression, no immune activation, & no significant change in HCV-specific plasma RNA

Clinical data • Hepatitis C Virus

SCY-635, alone and in combination with interferon alpha 2b, is highly effective in curing replicon cells of HCV RNA. (AASLD 2011) - Presentation time: Nov 05 2:00 PM - 7:30 PM; No significant enhancement of HCV RNA clearance was observed when adding rIFNα-2b in cultures treated with 1 μM SCY-635, indicating that SCY-635 was highly efficacious at this level in culture; SCY-635 was effective in clearing HCV-specific RNA from replicon cells and in preventing viral rebound at the end of treatment in vitro

Preclinical-other • Hepatitis C Virus