Monday, April 27, 2015

EASL 2015: Novira Therapeutics Announces Presentation of Preclinical Antiviral Data for NVR 3-778 at EASL

Oral presentation: "High antiviral activity of the HBV core inhibitor NVR 3-778 in the humanized UPA/SCID mouse model"

Poster presentation: "Effect of the combination of the HBV core inhibitor NVR 3-778 with nucleoside analogs or other HBV core inhibitors on the inhibition of HBV DNA replication in HepG2.2.15 cells"

DOYLESTOWN, Pa., April 27, 2015 /PRNewswire/ -- Novira Therapeutics, Inc., a privately held, clinical-stage biopharmaceutical company developing novel therapies for curative treatment of chronic hepatitis B virus (HBV) infection, today announced the presentation of preclinical antiviral data for its lead HBV core inhibitor candidate, NVR 3-778, at the 2015 annual meeting of the European Association for the Study of the Liver (EASL) in Vienna, Austria.

The antiviral activity of NVR 3-778 from studies performed in a humanized UPA/SCID mouse model was described in an oral presentation. As monotherapy given for a six week duration, NVR 3-778 showed HBV DNA suppression efficacy superior to pegylated interferon (PEG-IFN) and similar to that of the widely prescribed nucleoside analog entecavir. All mice responded to treatment and there was no evidence for drug resistance. The highest efficacy was observed in mice that received NVR 3-778 in combination with PEG-IFN, where all treated mice (n=11) reduced serum HBV DNA below the limit of quantitation.

In a poster session, Novira presented results from the combination of NVR 3-778 with nucleoside analogs lamivudine, tenofovir or entecavir in a cell-based model. These data showed additive and synergistic antiviral activity without cytotoxicity. NVR 3-778 also showed additive antiviral activity in combination with an HBV core inhibitor from another chemical class.

"The apparent synergy of NVR 3-778 in combination with PEG-IFN is very encouraging. This is the first time that we have seen a treatment with higher DNA suppression efficacy than entecavir in a humanized mouse model," said Klaus Klumpp, Ph.D., Novira's VP of Discovery and Biology. "Having access to a new class of Direct Acting Antivirals, or DAAs, enables the clinical testing of combination treatments that may significantly intensify the suppression of HBV production in the liver. Highly potent DAA combination treatment may be able to reduce the rate of new hepatocyte infection below that of infected hepatocyte clearance in HBV infected patients and may thereby lead to a clinically-relevant improvement in functional cure rates."

About NVR 3-778
NVR 3-778 is a small molecule, direct acting antiviral, for oral administration in patients with Chronic Hepatitis B (CHB) that inhibits the HBV core or capsid protein. HBV core is a novel and promising drug target with multiple activities required for viral replication and persistence. Inhibition of the HBV core protein function by NVR 3-778 offers the potential for more efficient suppression of virus production and replication, leading to improved durable viral suppression and functional cure rates. NVR 3-778 completed a Phase 1a clinical trial in 2014 and is currently enrolling a Phase 1b clinical trial.

About Novira Therapeutics
Novira Therapeutics, Inc., is a privately held biopharmaceutical company focused on discovery and development of first-in-class antiviral drugs for the treatment of chronic HBV infection (CHB), a global disease with a high level of unmet medical need. The company is employing innovative chemistry and biology technologies to discover small molecule inhibitors of the HBV core or capsid protein as well as other drugs with novel mode of action. The company's novel antivirals will offer the potential to address the limitations of current CHB therapies when used either as mono-therapy or in combination with existing standards of care.

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Spring Bank Pharmaceuticals Presents Preclinical and Clinical Data on Immunomodulatory Agent SB 9200 at the 2015 Annual Meeting of the European Association for the Study of the Liver

Animal Efficacy Studies in Chronically-Infected Woodchucks and Clinical Trial Results in Hepatitis C Patients Provide Support for Targeting RIG-I and NOD2 Sentinel Proteins to Restore Host Antiviral Defense

MILFORD, MA, USA I April 27, 2015 I 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 from its Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) programs at The International Liver Congress™ 2015, 50th annual meeting of the European Association for the Study of the Liver (EASL), April 22-26, in Vienna, Austria.

"The data presented at EASL on Saturday, April 25, continue to expand our understanding of the mechanism of action of SB 9200, an oral dinucleotide prodrug derived from our proprietary Small Molecule Nucleic Acid Hybrid (SMNH) technology platform," stated Radhakrishnan (Kris) Iyer, Ph.D., Chief Scientific Officer of Spring Bank. "Our studies demonstrate that SB 9200 activates the cell's innate immune response triggering Interferon production which causes the death of the infected cell thereby removing the virus while also providing protection for uninfected cells. Based on the results reported of a preclinical study in chronic hepatitis-carrier woodchucks and a Phase I study in HCV-infected patients, we are excited about the potential of SB 9200 for the treatment of HBV and HCV."

SB 9200 is an oral antiviral agent that uniquely acts by modulating the host immune response to viral infections through activation of host antiviral sensor proteins, RIG-I and NOD2.  RIG-1 and NOD2 are cytosolic viral sensors that are important for the regulation of the innate immune response and activation of intracellular interferon (IFN) signaling pathways in response to viral RNA. Data presented from a Phase I clinical study in HCV-infected patients with SB 9200 demonstrate safety, positive PK/PD characteristics and dose-dependent antiviral activity consistent with host immune modulation within infected cells.  Data presented from a 12-week study in the chronic woodchuck model of HBV infection demonstrate significant reductions in viral loads, surface antigen and cccDNA along with a strong safety profile, suggesting the potential of SB 9200 as a next generation HBV therapy in combination with currently available, direct acting HBV antiviral drugs as well as other agents in development.

"The data presented at EASL continue to build upon a growing body of scientific evidence supporting the development of SB 9200 in the treatment in HBV, HCV and other of viral diseases," said Douglas J. Jensen, President and CEO of Spring Bank. "Collectively, these data are helping to elucidate the underlying mechanisms that are the foundation for our research and development efforts with SB 9200. Based on the body of evidence we have assembled to date, we are  advancing SB 9200 into Phase II clinical trials in patients with HBV this year and evaluating opportunities to partner for Phase II combination studies in HCV."

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

Poster Presentations

Title: Antiviral Efficacy and Induction of Host Immune Responses with SB 9200, an Oral Prodrug of the Dinucleotide SB 9000, in the Woodchuck Model of Chronic Hepatitis B Virus (HBV) Infection
Date and Time: Saturday, April 25, 12:30 pm to 1:00 pm (CEST)
Location: Hall B ePoster Area
Abstract Number: PO636
Session: Viral hepatitis: Hepatitis B & D – c. Clinical (Therapy, new compounds, resistance)
An oral presentation of the poster was made by Dr. Stephan Menne, Research Associate Professor at the Department of Microbiology & Immunology, Georgetown University Medical Center

Summary: The study was a 12-week study in two groups of woodchucks with chronic woodchuck hepatitis virus (WHV) infection (the gold standard for HBV drug development). WHV carrier woodchucks (n=5/group) were treated orally, once daily, with SB 9200 for 12 weeks at doses of 15 or 30 mg/kg. Endpoints included PK, PD, tolerability, and efficacy determined by changes in serum levels of viral DNA, surface antigen (WHsAg), and antibody against WHsAg (anti-WHs). Efficacy in liver was evaluated by changes in levels of viral DNA, RNA, and antigens.

Treatment with SB 9200 at two select dose levels resulted in up to 4.2 and 2.2 log10 reductions in serum WHV DNA or WHsAg loads, respectively, from pretreatment levels. Treatment was also associated with reduced hepatic levels of WHV DNA replicative intermediate (RI) (up to 41%), WHV covalently-closed circular (ccc) DNA (up to 32%), and WHV RNA (up to 50%), lower hepatic expression of WHV core and surface antigens, and reduced liver disease progression. Following cessation of SB 9200 treatment, recrudescence of WHV replication was observed in all woodchucks treated with 15 mg/kg, whereas woodchucks administered 30 mg/kg had delays in the relapse of serum WHV DNA and WHsAg. The development of an anti-WHs antibody response was not observed in any of the woodchucks. Furthermore, the antiviral effects were associated with the dose-dependent induction of type I IFNs (IFN-α and IFN-β), ISGs (OAS-1, CXCL10, and ISG15), and cytokine (IL-6) in blood and liver. Prolonged SB 9200 administration at both dose levels was well tolerated with CBC, hematology and serum biochemistry parameters all appearing normal through the treatment period.

During this study, once-daily oral administration of SB 9200 in woodchucks with chronic WHV infection resulted in marked reductions in serum and hepatic levels of viral DNA, RNA, and antigens that were associated with (or were a result of) the induction of host immune responses. These results suggest that SB 9200 can induce an antiviral immune response during chronic active hepadnaviral infection that has the potential for a functional cure in the treatment of chronic hepatitis B, most likely in combination with approved anti-HBV drugs.

Title: SB 9200, A Novel Immunomodulator for Patients with Viral Hepatitis: Phase 1 MAD Study in
Patients with Hepatitis C Virus (HCV) Infection
Date and Time: Saturday, April 25, 2015, 3:30 pm to 4:00 pm (CEST)
Location: Hall B ePoster Area
Session: Late Breaker

Summary: This was a first in man randomized, placebo-controlled, multiple ascending dose study of SB 9200 in treatment-naïve, HCV-infected adults. Subjects were randomized 6:2 to SB 9200 or placebo for 7 days. Doses evaluated were 200 mg (N=8), 400 mg (N=8), 900 mg (N=8 HCV-1, N=6 HCV-3). The results showed that increases in SB 9200 AUC0-t and Cmax were dose-proportional. The terminal plasma half-life (t1/2) on Days 1 and 7 ranged from 0.684 to 1.07 hours for SB 9200, and was slightly longer for the metabolites: Sp-SB 9000 t1/2 was 4.65-8.90 hours, Rp-SB 9000 t1/2 was 4.31-5.94 hours. SB 9200 Cmax ranged from 0.531 to 6.66 ng/mL at 0.817 and 3.00 hours. Sp-SB 9000 Cmax ranged from 7.13 to 22.0 ng/mL at 1.00 and 12.0 hours. Rp-SB 9000 Cmax ranged from 4.32 to 14.7 ng/mL at 1.00 and 12.0 hours. Peak individual viral load drop improved from 1.5 to 1.9 log10 when the dose increased from 200 to 400 mg. Further dose increases did not result in response increases. Inter-individual variability in antiviral response was observed.

A significant relationship between SB 9200 Cmax and maximum suppression of HCV RNA on Day 7 was observed (p=0.015) after exclusion of two subjects with extreme Cmax values for SB 9200. Seventy-three adverse events (AEs) were reported by 25 subjects (83.3%), mostly mild in severity. No dose limiting toxicities or systemic interferon-like side effects were observed and no serious adverse events were reported. There was no relationship between incidences, severity or relationship of AEs and dose of SB 9200 received or placebo. Results of this study suggest an anti-viral effect similar to interferon but without systemic side effects. Based on the reported HCV data, Spring Bank believes SB9200 merits further evaluation in combination trials with direct-acting antivirals (DAAs).

About SB 9200
SB 9200, derived from Spring Bank's proprietary Small Molecule Nucleic Acid Hybrid (SMNH) technology platform, is a novel anti-viral agent that uniquely acts by modulating the host immune response to viral infections through activation of the intracellular sentinel proteins RIG-I and NOD2. SB 9200 is being developed for the treatment of chronic Hepatitis B and C and other viral infections.

About Spring Bank Pharmaceuticals
Spring Bank Pharmaceuticals is a clinical stage biopharmaceutical company. Based on its proprietary SMNH chemistry platform, Spring Bank is developing a pipeline of products representing a new class of pharmaceuticals with a wide range of applications. These rationally designed molecules combine the selectivity of naturally occurring nucleotides with the drug-like properties of classical pharmaceuticals.  The SMNHs have the properties of oral delivery, good pharmacokinetic profile, low side effects and ease of manufacture. The Company's most advanced clinical candidate, SB 9200, is a potential breakthrough drug for the treatment for HBV, HCV and other viral diseases. SB 9200 has a novel mechanism of action that involves modulation of the host immune response in the presence of viral infection.

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.

SOURCE: Spring Bank Pharmaceuticals

Thursday, April 23, 2015

BRIEF-Transgene presents new data for chronic hepatitis B treatment TG1050

* Transgene presents new data with TG1050, an immunotherapy being developed to treat chronic hepatitis B, at the international liver congress 2015

* Data presented demonstrate antiviral potential of TG1050 in a persistent hepatitis B virus (HBV) in vivo model

* TG1050 was shown to significantly reduce circulating HBV DNA, to reduce circulating HBV surface antigen, and to trigger seroconversion to HBsAg (i.e., to develop anti-HBsAg antibodies)

Source: Reuters

Tuesday, April 21, 2015

Inovio Pharmaceuticals and Roche Initiate Clinical Trial for Inovio's DNA Immunotherapy to Treat Chronic Hepatitis B Infection

PLYMOUTH MEETING, Pa., April 21, 2015 (GLOBE NEWSWIRE) -- Inovio Pharmaceuticals, Inc. (Nasdaq:INO) announced today that it has initiated a phase I trial to evaluate Inovio's DNA immunotherapy in patients who are chronically infected with hepatitis B. In 2013, Roche and Inovio entered into a partnership to co-develop and commercialize Inovio's hepatitis B immunotherapy. This trial initiation triggers a $3 million milestone payment from Roche to Inovio.

This phase I, randomized, open-label, active-controlled, dose escalation study will evaluate the safety, tolerability, and immunogenicity of Inovio's hepatitis B immunotherapy, INO-1800, alone or in combination with INO-9112, Inovio's IL-12-based immune activator. This international study will enroll patients in the United States and Asia Pacific region with a primary endpoint of safety and tolerability of the therapy. The secondary endpoints will evaluate the cellular and humoral immune response to INO-1800 and investigate the therapy's effect on several viral and antiviral parameters. All trial subjects are also medicated with standard-of-care antiviral therapies.

Monday, April 20, 2015

Cancer drug shows promise as cure for hepatitis B

 "Birinapant enabled the destruction of hepatitis B-infected liver cells while leaving normal cells unharmed. Excitingly, when birinapant was administered in combination with current antiviral drug entecavir, the infection was cleared twice as fast compared with birinapant alone."

Australian scientists have found a potential cure for hepatitis B virus (HBV) infections, with a promising new treatment proving 100 per cent successful in eliminating the infection in preclinical models.

Australian patients are now the first in the world to have access to the potential treatment - a combination of an antiviral drug and an anti-cancer drug - which is in phase 1/2a clinical trials in Melbourne, Perth and Adelaide.

Scientists from Melbourne's Walter and Eliza Hall Institute developed the combination treatment using birinapant, a drug developed by US biotech company TetraLogic Pharmaceuticals for treating cancer. Hepatitis B is a chronic viral disease that is currently incurable.


Saturday, April 18, 2015

Ichor, Janssen Announce Chronic Hepatitis B Immunotherapies Delivered With TriGrid Electroporation Device

Ichor Medical Systems (Ichor) recently announced it has joined a product advancement collaboration and license agreement with Janssen Pharmaceuticals (Janssen). Both parties will be working together to advance and market DNA-based vaccine products to treat patients with chronic hepatitis B clinically administered through the Company’s TriGrid™ electroporation technology. Ichor will be receiving R&D development and support, an upfront payment and additional sales payments up to a total of $85 million, as well as royalty payments resulting from any licensed product sales in the future. Janssen will take responsibility for development and commercialization costs that might result from the program such as for distribution and manufacturing expenses for Ichor’s TriGrid Delivery System.

DNA vaccines are capable of generating antigen-specific antibodies and T cells crucial to treat the HBV infection over the long-term. However, the effectiveness of DNA vaccines when delivered through the conventional injection approach yields poor results. Electroporation — the technology behind Ichor’s TriGrid drug delivery system — is a strong and effective method to deliver vaccines. It uses weak electrical pulses to alter cell membranes and to ease the entrance of DNA into cells. The TriGrid Delivery System by Ichor is currently under testing in clinical trials, becoming the first integrated and completely automated technology to be used in humans and for electroporation-mediated DNA administration. Previous assessments evidenced that the TriGrid can significantly enhance immune responses and the delivery of vaccines if compared to the conventional approaches such as via ordinary injection.


Tuesday, April 14, 2015

HBV vaccine unaffected by diabetes

BETHESDA, Md. — There is no statistical evidence that type 2 diabetes negatively affects immune response to hepatitis B vaccine, according to findings presented at the Annual Conference on Vaccine Research.

 In 2011, the Advisory Committee on Immunization Practices recommended that patients aged 19 to 59 years should be vaccinated against HBV as soon as possible after a diagnosis of diabetes, and for those aged 60 years and older, the HBV vaccine may be administered at the clinician’s discretion. These recommendations were made primarily because patients with diabetes are at an increased risk for HBV, Andrew Trofa, MD, of GlaxoSmithKline Biologicals, said during his presentation. However, there are limited data from prospective clinical trials of HBV vaccination in people with diabetes, he said.

In a phase 4, open-label, international trial, Trofa and colleagues assessed the seroprotection rate of the three-dose HBV vaccine series in adult men and women with type 2 diabetes who had no history of HBV infection or vaccination. The study included 512 participants with type 2 diabetes and 256 controls without diabetes who were stratified into eight subgroups by age (20-39 years, 40-49 years, 50-59 years, and 60 years and older) and BMI (< 30 and ≥ 30). Seroprotection was defined as antibodies to hepatitis B surface antigen (anti-HBs) of at least 10 mIU/mL.