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Spring Bank Pharmaceuticals Presents Data on Immunomodulatory Agent SB 9200 at the 29th International Conference on Antiviral Research

MILFORD, Mass., April 21, 2016 (GLOBE NEWSWIRE) -- Spring Bank Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company developing novel therapeutics for the treatment of viral infections, today announced the presentation of scientific data relating to its hepatitis B virus (HBV) and respiratory syncytial virus (RSV) research programs at the 29th International Conference on Antiviral Research (ICAR), which took place April 17-21, in La Jolla, CA.

“The data presented at this year’s ICAR annual meeting are important because they provide further scientific evidence supporting SB 9200’s potential as a first-in-class oral antiviral agent,” stated Radhakrishnan (Kris) Iyer, PhD, Chief Scientific Officer of Spring Bank. “Among the key findings reported were that SB 9200’s antiviral activity was mediated by a dose-dependent and long-lasting immune response in the woodchuck model of chronic HBV, which is considered the most suitable animal model for chronic HBV. We also reported on studies in rats in which SB 9200 was rapidly and efficiently converted into its active form, which was then transported into hepatocytes from blood. If this effect was seen in humans it would translate into the potential for high exposure of the compound in the liver with low non-liver systemic exposure for patients. Evaluation in the WHV-infected woodchucks demonstrated significant reductions in viral loads, surface antigen and covalently closed circular DNA.”

Dr. Iyer continued, “Further, we tested SB 9200 in preclinical models of respiratory syncytial virus (RSV), a serious lower respiratory tract infection for which there is currently no treatment. Consistent with its mechanism of action, treatment with SB 9200 in RSV-infected mice resulted in significant reduction in viral load, in pro-inflammatory cytokines and in lung inflammation, leading to unobstructed airways that were nearly similar to that of the uninfected control group.”

Spring Bank believes that the data presented supports its ongoing research program targeting chronic HBV by modulating the host immune response to viral infections through activation of RIG-I and NOD2 with once daily oral administration of SB 9200.

A summary of the data presented by Spring Bank at the conference is below:

Poster Presentations

Poster Title: Activation and induction of immune response genes RIG-I, STING, and NOD2 in the antiviral activity of SB 9200 in the woodchuck model of chronic Hepatitis B
Date and Time: Monday, April 18, 2016, 4:30 – 6:30 pm
Abstract Number: 044
Session Title: Poster Session 1
Summary: SB 9200 is an orally available dinucleotide that activates the cellular viral sensors RIG-I and NOD2 causing the induction of interferon (IFN) signaling cascade for antiviral defense. This study aimed to evaluate the expression of RIG-I, NOD2, STING, IRF3, IRF7, and other antiviral cytokines associated with the antiviral activity of SB 9200.

The study results demonstrated that orally administered SB 9200 induced dose-dependent and long-lasting expression of type I IFNs and ISGs, and antiviral cytokines in blood and liver of woodchucks. SB 9200 treatment also induced the expression of RIG-I, NOD2, STING, IRF3, and IRF7 in the liver compared to pretreatment levels. The expression of all genes was significantly induced during treatment and follow-up. These results support the thesis that the anti-viral activity of SB 9200 in woodchucks is associated with activation and induction of the host-immune response genes.

Poster Title: SB 9200, a novel antiviral agent, targets liver after oral administration to rats
Date and Time: Monday, April 18, 2016, 4:30 – 6:30 pm
Poster Number: 047
Session Title: Poster Session 1
Summary: SB 9200 is an orally available dinucleotide prodrug designed to target the liver and is a potent antiviral agent against HBV, HCV, RSV and Norovirus. This preclinical study evaluated the disposition of SB 9200 in the liver of rats following three months of daily oral dosing. The prodrug SB 9200 is rapidly converted to its active SB 9000 in blood, and therefore, SB 9000 was monitored in this study.

Multiple peak levels of SB 9000 were observed in plasma consistent with enterohepatic cycling. SB 9000 distributed to the liver with levels 20 to 40-fold higher than plasma with clearance 24-hr post-dose after three months of daily dosing. The plasma bioavailability of SB 9000 was below 3%, however, consistent with a large first-pass uptake of SB 9000 into the liver from the portal blood, 58% of the SB 9000 administered after oral dosing of SB 9200 was found in the liver compared with levels after IV dosing. These results suggest that SB 9000 is actively transported via organic anion transporters into hepatocytes from the portal blood. Thus, oral administration of SB 9200 could potentially lead to high exposure in the liver with low non-hepatic systemic exposure in patients.

Poster Title: Prophylactic and therapeutic anti-RSV activity of SB 9200 – a novel agent that activates RIG-I and NOD2
Date and Time: Monday, April 18, 2016, 4:30 – 6:30 pm
Abstract Number: 041
Session Title: Poster Session 1
Summary: Respiratory syncytial virus (RSV) causes lower respiratory tract infections in infants and other high-risk populations, leading to substantial morbidity and mortality. Currently, there is no treatment for RSV and a significant unmet need exists for developing anti-RSV agents. This study aimed to evaluate in vitro and in vivo the anti-RSV activity of SB 9200, an oral innate immune modulator that has demonstrated potent antiviral activity against HBV, HCV, and Norovirus.

Prophylactic and therapeutic studies conducted in the mouse model of RSV demonstrated that SB 9200 treatment significantly reduced lung inflammation leading to unobstructed airway spaces almost similar to that of uninfected control group. In addition, SB 9200 significantly reduced viral burden and RSV nucleocapsid expression, and caused strong induction of IFN-beta, along with a significant reduction in pro-inflammatory cytokines - IL-6 and TNF-alpha. These results support the thesis that SB 9200 may diminish disease severity associated with RSV infection consistent with SB 9200’s novel mechanisms of action.

Poster Title: In vitro metabolism, CYP inhibitory potential and transporter studies of SB 9200 – a novel broad-spectrum antiviral agent
Date and Time: Wednesday, April 20, 2016, 4:30 – 6:30 pm
Poster Number: 048
Session Title: Poster Session 2
Summary: The objective of this study was to evaluate in vitro metabolism, CYP inhibitory activity, and transport characteristics of SB 9200. SB 9200 was incubated with pooled mixed gender human, Beagle dog, Sprague-Dawley rat and cynomologus macaque liver microsomes and S9 fractions.

The study results demonstrated that the prodrug SB 9200 was rapidly converted to the active SB 9000 in the presence of liver microsomes, and the SB 9000 was found to be metabolically stable with no observed sulfation or glucuronidation. No effect on enzymatic activities of CYP isoforms was observed. SB 9000 was found to be a substrate for OAT1, OAT3, OATP1B1 and OATP1B3 transporters. These results suggest that SB 9200 prodrug is efficiently converted to the active SB 9000 in various animal models, which has no inhibitory effect on CYP isoforms and that in these models SB 9000 appears to be a substrate for organic anion transporters that might facilitate its absorption via active transport.

About Spring Bank Pharmaceuticals

Spring Bank Pharmaceuticals is a clinical-stage biopharmaceutical company engaged in the discovery and development of a novel class of therapeutics using its proprietary small molecule nucleic acid hybrid, or SMNH, chemistry platform. SMNH compounds are small segments of nucleic acids that the company designs to selectively target and modulate the activity of specific proteins implicated in various disease states. The company is developing its most advanced SMNH product candidate, SB 9200, for the treatment of viral diseases. SB 9200 has been designed to selectively activate within infected cells the cellular proteins, retinoic acid-inducible gene 1, or RIG-I, and nucleotide-binding oligomerization domain-containing protein 2, or NOD2, which have been implicated in the body’s immune response to viral infections. Spring Bank believes that SB 9200 may play an important role in antiviral therapy by modulating the body’s immune response through its mechanisms of action to fight viral infections such as HBV and RSV.

Note Regarding NIH-Funded Research

Certain studies mentioned in this press release were partly supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number R01AI094469 and NIAID contract laboratories. The content of this press release is solely the responsibility of Spring Bank Pharmaceuticals and does not necessarily represent the official views of the National Institutes of Health.

Contact: Maeve Conneighton Argot Partners (212) 600-1902 maeve@argotpartners.com

Source: Spring Bank Pharmaceuticals, Inc.