Victorian Infectious Diseases Reference Laboratory

North Melbourne, Australia

Victorian Infectious Diseases Reference Laboratory

North Melbourne, Australia
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SB 9200 Shows Favorable Safety Profile and Significant Antiviral Activity Against HBV DNA and HBsAg with Initial Low Dose Monotherapy of 25mg Conference Call Scheduled for Tomorrow, May 24th at 8:00 a.m. ET HOPKINTON, Mass., May 23, 2017 (GLOBE NEWSWIRE) -- Spring Bank Pharmaceuticals, Inc. (Nasdaq:SBPH) announced today the top-line results from the 25mg monotherapy cohort of the Phase 2a segment of the ACHIEVE study, a global, placebo-controlled, sequential-cohort, double-blind Phase 2 clinical trial, focused on the safety and antiviral activity of the orally-administered selective immunomodulator, SB 9200, in patients with chronic HBV. The initial cohort of the Phase 2a trial enrolled twenty (20) treatment-naïve chronic HBV patients without cirrhosis across multiple sites in Canada, Hong Kong and Korea.  Patients were randomized on a 4:1 basis and received either SB 9200 25mg or placebo daily for 12 weeks. The primary endpoints for the Phase 2a trial are safety and antiviral activity, as measured by the change in HBV DNA at week 12 from baseline, with multiple exploratory secondary endpoints. All patients in this cohort have transitioned to tenofovir disoproxil fumarate (marketed by Gilead Sciences, Inc. as Viread®) 300mg daily for an additional 12 weeks. “We are strongly encouraged by the safety profile of SB 9200 seen in this initial cohort of the Phase 2a trial and by the evidence of antiviral activity seen at the low dose of 25mg daily, because we studied the substantially higher doses of 200mg – 900mg daily for 7 days in our Phase 1 study in HCV patients,” stated Nezam Afdhal, M.D., D.Sc., Chief Medical Officer of Spring Bank Pharmaceuticals.  “The results from the initial cohort of the Phase 2a trial continue to support the development of SB 9200 as a potential treatment for chronic HBV to achieve the goal of a functional cure.  We have begun to rapidly enroll the second cohort (50 mg) of our Phase 2a trial and hope to report top-line results in the fourth quarter of 2017.” The initial cohort consisted of 11 HBeAg-positive and 9 HBeAg-negative patients, of which 80% were genotype B/C, the most common Asian genotypes. The overall safety profile of SB 9200 was favorable, and over the 12-week study, no serious adverse events were observed. Treatment-emergent adverse events ranged from mild to moderate in severity with no interferon-like side effects and were comparable to patients on placebo. There were no Grade 3 laboratory abnormalities, but alanine aminotransferase (ALT) flares, defined as an increase in ALT above 200 IU/ml, were observed in three patients. Two of these ALT flares were viral flares identified in patients on placebo and the other ALT flare was identified in one patient on SB 9200 at week 4, which was associated with a reduction in HBV DNA of 2.26 log and a 1.01 log reduction in HBsAg consistent with a beneficial immune flare. Study investigators did not observe any increase in bilirubin or evidence of hepatic decompensation. Overall, SB 9200 demonstrated a statistically significant reduction in HBV DNA at week 12 (unpaired t-test 2.85, p=0.01) compared to placebo, with a mean reduction of 0.6 log (range 0 to 1.87 log ) in the SB 9200 treatment group. For the secondary endpoint of quantitative HBsAg reduction, 5 of 16 patients (31%) in the SB 9200 treatment group had a greater than 0.5 log reduction at any time point (range 0.52 to 1.01 log ), compared to none in the placebo group. The 7 HBeAg-negative patients in the SB 9200 treatment group had the greatest mean reduction in HBV DNA at 0.9 log , and 3 of these 7 patients also had a greater than 0.5 log reduction in HBsAg. Professor Stephen Locarnini, the Principal Investigator of the Virology Core for the ACHIEVE trial and the Head, Research & Molecular Development, Victorian Infectious Diseases Reference Laboratory, stated, “Our virological studies from the first cohort showed antiviral activity of SB 9200 involving a novel immune and possibly direct antiviral mechanism targeting RIG-I, resulting in not only reduction in HBV DNA but also in HBsAg and HBV pgRNA as a surrogate for reduction in cccDNA.” Detailed results from the Phase 2a segment of the ACHIEVE study will be presented at a future medical conference. Spring Bank Pharmaceuticals will host a conference call at 8:00 a.m. ET tomorrow, Wednesday, May 24, 2017, to discuss top-line results of the initial cohort of the Phase 2a segment of the ACHIEVE study. The conference call may be accessed by dialing (866) 294-9216 for U.S. callers and (346) 406-0955 for international callers five minutes prior to the start of the call and providing the conference ID 27754723. Additionally, the live, listen-only webcast of the conference call can be accessed by visiting the Investors & Media section of the company’s website at www.springbankpharm.com. A replay of the conference call will be available following the call and may be accessed by visiting Spring Bank’s website. About SB 9200 and the ACHIEVE Study Spring Bank’s lead product candidate, SB 9200 is a novel small molecule nucleic acid hybrid (SMNH) compound being developed as both monotherapy and combination therapy for the treatment of chronic HBV.  The Phase 2a clinical trial is designed to enable Spring Bank to select one or two doses to move forward into a Phase 2b clinical trial and to obtain the necessary dosing and safety data to study the combined use of SB 9200 and a direct-acting antiviral. The first segment of the ACHIEVE trial is a Phase 2a placebo-controlled, sequential-cohort, double-blind trial to evaluate increasing doses of SB 9200 as monotherapy for 12 weeks followed by Viread® 300 mg for an additional 12 weeks.  The Phase 2a segment of the ACHIEVE trial has an adaptive trial design that will enroll 80 chronically-infected HBV patients between 18 and 70 years of age who have been or will be assigned to one of four dosing cohorts, 25 mg, 50 mg, 100 mg or 200 mg of SB 9200, or placebo, once daily for 12 weeks. All subjects will then receive Viread® 300 mg once daily for an additional 12 weeks of treatment. The Phase 2b segment of the ACHIEVE trial is planned to examine the concomitant use of SB 9200 and Viread® in approximately 200 HBV patients. Subject to the results of the Phase 2a clinical trial and obtaining additional funding, Spring Bank plans to initiate the Phase 2b segment of the ACHIEVE trial in 2018. 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 (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, including hepatitis B virus (HBV). 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 Pharmaceuticals is also developing other SMNH product candidates, including SB 11285, the company’s lead immunotherapeutic agent for the treatment of selected cancers through the activation of the STimulator of INterferon Genes, or STING, pathway. For more information, please visit www.springbankpharm.com Statements in this press release about Spring Bank’s future expectations, plans and prospects, including, but not limited to, statements about the company’s expectations for the enrollment of patients in the second cohort of the Phase 2a segment of the ACHIEVE trial; the company’s anticipated timeline for disclosing top-line results from the second cohort of the Phase 2a segment of the ACHIEVE trial and the company’s anticipated timeline for initiating the Phase 2b segment of the ACHIEVE trial, as well as any other statements regarding matters that are not historical facts, may constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including whether Spring Bank’s cash resources will be sufficient to fund its continuing operations for the periods and/or trials anticipated; whether results obtained in preclinical studies and clinical trials will be indicative of results obtained in future clinical trials; whether Spring Bank’s product candidates will advance through the clinical trial process on a timely basis, or at all; whether the results of such trials will warrant submission for approval from the United States Food and Drug Administration or equivalent foreign regulatory agencies; whether Spring Bank’s product candidates will receive approval from regulatory agencies on a timely basis or at all; whether, if product candidates obtain approval, they will be successfully distributed and marketed; and other factors discussed in the "Risk Factors" section of Spring Bank’s Annual Report on Form 10-K for the year ended December 31, 2016, which was filed with the Securities and Exchange Commission (SEC) on February 14, 2017, and in other filings Spring Bank makes with the SEC from time to time. In addition, the forward-looking statements included in this press release represent Spring Bank’s views as of the date hereof. Spring Bank anticipates that subsequent events and developments will cause Spring Bank’s views to change. However, while Spring Bank may elect to update these forward-looking statements at some point in the future, Spring Bank specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Spring Bank’s views as of any date subsequent to the date hereof.


SB 9200 Shows Favorable Safety Profile and Significant Antiviral Activity Against HBV DNA and HBsAg with Initial Low Dose Monotherapy of 25mg Conference Call Scheduled for Tomorrow, May 24th at 8:00 a.m. ET HOPKINTON, Mass., May 23, 2017 (GLOBE NEWSWIRE) -- Spring Bank Pharmaceuticals, Inc. (Nasdaq:SBPH) announced today the top-line results from the 25mg monotherapy cohort of the Phase 2a segment of the ACHIEVE study, a global, placebo-controlled, sequential-cohort, double-blind Phase 2 clinical trial, focused on the safety and antiviral activity of the orally-administered selective immunomodulator, SB 9200, in patients with chronic HBV. The initial cohort of the Phase 2a trial enrolled twenty (20) treatment-naïve chronic HBV patients without cirrhosis across multiple sites in Canada, Hong Kong and Korea.  Patients were randomized on a 4:1 basis and received either SB 9200 25mg or placebo daily for 12 weeks. The primary endpoints for the Phase 2a trial are safety and antiviral activity, as measured by the change in HBV DNA at week 12 from baseline, with multiple exploratory secondary endpoints. All patients in this cohort have transitioned to tenofovir disoproxil fumarate (marketed by Gilead Sciences, Inc. as Viread®) 300mg daily for an additional 12 weeks. “We are strongly encouraged by the safety profile of SB 9200 seen in this initial cohort of the Phase 2a trial and by the evidence of antiviral activity seen at the low dose of 25mg daily, because we studied the substantially higher doses of 200mg – 900mg daily for 7 days in our Phase 1 study in HCV patients,” stated Nezam Afdhal, M.D., D.Sc., Chief Medical Officer of Spring Bank Pharmaceuticals.  “The results from the initial cohort of the Phase 2a trial continue to support the development of SB 9200 as a potential treatment for chronic HBV to achieve the goal of a functional cure.  We have begun to rapidly enroll the second cohort (50 mg) of our Phase 2a trial and hope to report top-line results in the fourth quarter of 2017.” The initial cohort consisted of 11 HBeAg-positive and 9 HBeAg-negative patients, of which 80% were genotype B/C, the most common Asian genotypes. The overall safety profile of SB 9200 was favorable, and over the 12-week study, no serious adverse events were observed. Treatment-emergent adverse events ranged from mild to moderate in severity with no interferon-like side effects and were comparable to patients on placebo. There were no Grade 3 laboratory abnormalities, but alanine aminotransferase (ALT) flares, defined as an increase in ALT above 200 IU/ml, were observed in three patients. Two of these ALT flares were viral flares identified in patients on placebo and the other ALT flare was identified in one patient on SB 9200 at week 4, which was associated with a reduction in HBV DNA of 2.26 log and a 1.01 log reduction in HBsAg consistent with a beneficial immune flare. Study investigators did not observe any increase in bilirubin or evidence of hepatic decompensation. Overall, SB 9200 demonstrated a statistically significant reduction in HBV DNA at week 12 (unpaired t-test 2.85, p=0.01) compared to placebo, with a mean reduction of 0.6 log (range 0 to 1.87 log ) in the SB 9200 treatment group. For the secondary endpoint of quantitative HBsAg reduction, 5 of 16 patients (31%) in the SB 9200 treatment group had a greater than 0.5 log reduction at any time point (range 0.52 to 1.01 log ), compared to none in the placebo group. The 7 HBeAg-negative patients in the SB 9200 treatment group had the greatest mean reduction in HBV DNA at 0.9 log , and 3 of these 7 patients also had a greater than 0.5 log reduction in HBsAg. Professor Stephen Locarnini, the Principal Investigator of the Virology Core for the ACHIEVE trial and the Head, Research & Molecular Development, Victorian Infectious Diseases Reference Laboratory, stated, “Our virological studies from the first cohort showed antiviral activity of SB 9200 involving a novel immune and possibly direct antiviral mechanism targeting RIG-I, resulting in not only reduction in HBV DNA but also in HBsAg and HBV pgRNA as a surrogate for reduction in cccDNA.” Detailed results from the Phase 2a segment of the ACHIEVE study will be presented at a future medical conference. Spring Bank Pharmaceuticals will host a conference call at 8:00 a.m. ET tomorrow, Wednesday, May 24, 2017, to discuss top-line results of the initial cohort of the Phase 2a segment of the ACHIEVE study. The conference call may be accessed by dialing (866) 294-9216 for U.S. callers and (346) 406-0955 for international callers five minutes prior to the start of the call and providing the conference ID 27754723. Additionally, the live, listen-only webcast of the conference call can be accessed by visiting the Investors & Media section of the company’s website at www.springbankpharm.com. A replay of the conference call will be available following the call and may be accessed by visiting Spring Bank’s website. About SB 9200 and the ACHIEVE Study Spring Bank’s lead product candidate, SB 9200 is a novel small molecule nucleic acid hybrid (SMNH) compound being developed as both monotherapy and combination therapy for the treatment of chronic HBV.  The Phase 2a clinical trial is designed to enable Spring Bank to select one or two doses to move forward into a Phase 2b clinical trial and to obtain the necessary dosing and safety data to study the combined use of SB 9200 and a direct-acting antiviral. The first segment of the ACHIEVE trial is a Phase 2a placebo-controlled, sequential-cohort, double-blind trial to evaluate increasing doses of SB 9200 as monotherapy for 12 weeks followed by Viread® 300 mg for an additional 12 weeks.  The Phase 2a segment of the ACHIEVE trial has an adaptive trial design that will enroll 80 chronically-infected HBV patients between 18 and 70 years of age who have been or will be assigned to one of four dosing cohorts, 25 mg, 50 mg, 100 mg or 200 mg of SB 9200, or placebo, once daily for 12 weeks. All subjects will then receive Viread® 300 mg once daily for an additional 12 weeks of treatment. The Phase 2b segment of the ACHIEVE trial is planned to examine the concomitant use of SB 9200 and Viread® in approximately 200 HBV patients. Subject to the results of the Phase 2a clinical trial and obtaining additional funding, Spring Bank plans to initiate the Phase 2b segment of the ACHIEVE trial in 2018. 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 (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, including hepatitis B virus (HBV). 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 Pharmaceuticals is also developing other SMNH product candidates, including SB 11285, the company’s lead immunotherapeutic agent for the treatment of selected cancers through the activation of the STimulator of INterferon Genes, or STING, pathway. For more information, please visit www.springbankpharm.com Statements in this press release about Spring Bank’s future expectations, plans and prospects, including, but not limited to, statements about the company’s expectations for the enrollment of patients in the second cohort of the Phase 2a segment of the ACHIEVE trial; the company’s anticipated timeline for disclosing top-line results from the second cohort of the Phase 2a segment of the ACHIEVE trial and the company’s anticipated timeline for initiating the Phase 2b segment of the ACHIEVE trial, as well as any other statements regarding matters that are not historical facts, may constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including whether Spring Bank’s cash resources will be sufficient to fund its continuing operations for the periods and/or trials anticipated; whether results obtained in preclinical studies and clinical trials will be indicative of results obtained in future clinical trials; whether Spring Bank’s product candidates will advance through the clinical trial process on a timely basis, or at all; whether the results of such trials will warrant submission for approval from the United States Food and Drug Administration or equivalent foreign regulatory agencies; whether Spring Bank’s product candidates will receive approval from regulatory agencies on a timely basis or at all; whether, if product candidates obtain approval, they will be successfully distributed and marketed; and other factors discussed in the "Risk Factors" section of Spring Bank’s Annual Report on Form 10-K for the year ended December 31, 2016, which was filed with the Securities and Exchange Commission (SEC) on February 14, 2017, and in other filings Spring Bank makes with the SEC from time to time. In addition, the forward-looking statements included in this press release represent Spring Bank’s views as of the date hereof. Spring Bank anticipates that subsequent events and developments will cause Spring Bank’s views to change. However, while Spring Bank may elect to update these forward-looking statements at some point in the future, Spring Bank specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Spring Bank’s views as of any date subsequent to the date hereof.


SB 9200 Shows Favorable Safety Profile and Significant Antiviral Activity Against HBV DNA and HBsAg with Initial Low Dose Monotherapy of 25mg Conference Call Scheduled for Tomorrow, May 24th at 8:00 a.m. ET HOPKINTON, Mass., May 23, 2017 (GLOBE NEWSWIRE) -- Spring Bank Pharmaceuticals, Inc. (Nasdaq:SBPH) announced today the top-line results from the 25mg monotherapy cohort of the Phase 2a segment of the ACHIEVE study, a global, placebo-controlled, sequential-cohort, double-blind Phase 2 clinical trial, focused on the safety and antiviral activity of the orally-administered selective immunomodulator, SB 9200, in patients with chronic HBV. The initial cohort of the Phase 2a trial enrolled twenty (20) treatment-naïve chronic HBV patients without cirrhosis across multiple sites in Canada, Hong Kong and Korea.  Patients were randomized on a 4:1 basis and received either SB 9200 25mg or placebo daily for 12 weeks. The primary endpoints for the Phase 2a trial are safety and antiviral activity, as measured by the change in HBV DNA at week 12 from baseline, with multiple exploratory secondary endpoints. All patients in this cohort have transitioned to tenofovir disoproxil fumarate (marketed by Gilead Sciences, Inc. as Viread®) 300mg daily for an additional 12 weeks. “We are strongly encouraged by the safety profile of SB 9200 seen in this initial cohort of the Phase 2a trial and by the evidence of antiviral activity seen at the low dose of 25mg daily, because we studied the substantially higher doses of 200mg – 900mg daily for 7 days in our Phase 1 study in HCV patients,” stated Nezam Afdhal, M.D., D.Sc., Chief Medical Officer of Spring Bank Pharmaceuticals.  “The results from the initial cohort of the Phase 2a trial continue to support the development of SB 9200 as a potential treatment for chronic HBV to achieve the goal of a functional cure.  We have begun to rapidly enroll the second cohort (50 mg) of our Phase 2a trial and hope to report top-line results in the fourth quarter of 2017.” The initial cohort consisted of 11 HBeAg-positive and 9 HBeAg-negative patients, of which 80% were genotype B/C, the most common Asian genotypes. The overall safety profile of SB 9200 was favorable, and over the 12-week study, no serious adverse events were observed. Treatment-emergent adverse events ranged from mild to moderate in severity with no interferon-like side effects and were comparable to patients on placebo. There were no Grade 3 laboratory abnormalities, but alanine aminotransferase (ALT) flares, defined as an increase in ALT above 200 IU/ml, were observed in three patients. Two of these ALT flares were viral flares identified in patients on placebo and the other ALT flare was identified in one patient on SB 9200 at week 4, which was associated with a reduction in HBV DNA of 2.26 log and a 1.01 log reduction in HBsAg consistent with a beneficial immune flare. Study investigators did not observe any increase in bilirubin or evidence of hepatic decompensation. Overall, SB 9200 demonstrated a statistically significant reduction in HBV DNA at week 12 (unpaired t-test 2.85, p=0.01) compared to placebo, with a mean reduction of 0.6 log (range 0 to 1.87 log ) in the SB 9200 treatment group. For the secondary endpoint of quantitative HBsAg reduction, 5 of 16 patients (31%) in the SB 9200 treatment group had a greater than 0.5 log reduction at any time point (range 0.52 to 1.01 log ), compared to none in the placebo group. The 7 HBeAg-negative patients in the SB 9200 treatment group had the greatest mean reduction in HBV DNA at 0.9 log , and 3 of these 7 patients also had a greater than 0.5 log reduction in HBsAg. Professor Stephen Locarnini, the Principal Investigator of the Virology Core for the ACHIEVE trial and the Head, Research & Molecular Development, Victorian Infectious Diseases Reference Laboratory, stated, “Our virological studies from the first cohort showed antiviral activity of SB 9200 involving a novel immune and possibly direct antiviral mechanism targeting RIG-I, resulting in not only reduction in HBV DNA but also in HBsAg and HBV pgRNA as a surrogate for reduction in cccDNA.” Detailed results from the Phase 2a segment of the ACHIEVE study will be presented at a future medical conference. Spring Bank Pharmaceuticals will host a conference call at 8:00 a.m. ET tomorrow, Wednesday, May 24, 2017, to discuss top-line results of the initial cohort of the Phase 2a segment of the ACHIEVE study. The conference call may be accessed by dialing (866) 294-9216 for U.S. callers and (346) 406-0955 for international callers five minutes prior to the start of the call and providing the conference ID 27754723. Additionally, the live, listen-only webcast of the conference call can be accessed by visiting the Investors & Media section of the company’s website at www.springbankpharm.com. A replay of the conference call will be available following the call and may be accessed by visiting Spring Bank’s website. About SB 9200 and the ACHIEVE Study Spring Bank’s lead product candidate, SB 9200 is a novel small molecule nucleic acid hybrid (SMNH) compound being developed as both monotherapy and combination therapy for the treatment of chronic HBV.  The Phase 2a clinical trial is designed to enable Spring Bank to select one or two doses to move forward into a Phase 2b clinical trial and to obtain the necessary dosing and safety data to study the combined use of SB 9200 and a direct-acting antiviral. The first segment of the ACHIEVE trial is a Phase 2a placebo-controlled, sequential-cohort, double-blind trial to evaluate increasing doses of SB 9200 as monotherapy for 12 weeks followed by Viread® 300 mg for an additional 12 weeks.  The Phase 2a segment of the ACHIEVE trial has an adaptive trial design that will enroll 80 chronically-infected HBV patients between 18 and 70 years of age who have been or will be assigned to one of four dosing cohorts, 25 mg, 50 mg, 100 mg or 200 mg of SB 9200, or placebo, once daily for 12 weeks. All subjects will then receive Viread® 300 mg once daily for an additional 12 weeks of treatment. The Phase 2b segment of the ACHIEVE trial is planned to examine the concomitant use of SB 9200 and Viread® in approximately 200 HBV patients. Subject to the results of the Phase 2a clinical trial and obtaining additional funding, Spring Bank plans to initiate the Phase 2b segment of the ACHIEVE trial in 2018. 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 (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, including hepatitis B virus (HBV). 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 Pharmaceuticals is also developing other SMNH product candidates, including SB 11285, the company’s lead immunotherapeutic agent for the treatment of selected cancers through the activation of the STimulator of INterferon Genes, or STING, pathway. For more information, please visit www.springbankpharm.com Statements in this press release about Spring Bank’s future expectations, plans and prospects, including, but not limited to, statements about the company’s expectations for the enrollment of patients in the second cohort of the Phase 2a segment of the ACHIEVE trial; the company’s anticipated timeline for disclosing top-line results from the second cohort of the Phase 2a segment of the ACHIEVE trial and the company’s anticipated timeline for initiating the Phase 2b segment of the ACHIEVE trial, as well as any other statements regarding matters that are not historical facts, may constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including whether Spring Bank’s cash resources will be sufficient to fund its continuing operations for the periods and/or trials anticipated; whether results obtained in preclinical studies and clinical trials will be indicative of results obtained in future clinical trials; whether Spring Bank’s product candidates will advance through the clinical trial process on a timely basis, or at all; whether the results of such trials will warrant submission for approval from the United States Food and Drug Administration or equivalent foreign regulatory agencies; whether Spring Bank’s product candidates will receive approval from regulatory agencies on a timely basis or at all; whether, if product candidates obtain approval, they will be successfully distributed and marketed; and other factors discussed in the "Risk Factors" section of Spring Bank’s Annual Report on Form 10-K for the year ended December 31, 2016, which was filed with the Securities and Exchange Commission (SEC) on February 14, 2017, and in other filings Spring Bank makes with the SEC from time to time. In addition, the forward-looking statements included in this press release represent Spring Bank’s views as of the date hereof. Spring Bank anticipates that subsequent events and developments will cause Spring Bank’s views to change. However, while Spring Bank may elect to update these forward-looking statements at some point in the future, Spring Bank specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Spring Bank’s views as of any date subsequent to the date hereof.


SB 9200 Shows Favorable Safety Profile and Significant Antiviral Activity Against HBV DNA and HBsAg with Initial Low Dose Monotherapy of 25mg Conference Call Scheduled for Tomorrow, May 24th at 8:00 a.m. ET HOPKINTON, Mass., May 23, 2017 (GLOBE NEWSWIRE) -- Spring Bank Pharmaceuticals, Inc. (Nasdaq:SBPH) announced today the top-line results from the 25mg monotherapy cohort of the Phase 2a segment of the ACHIEVE study, a global, placebo-controlled, sequential-cohort, double-blind Phase 2 clinical trial, focused on the safety and antiviral activity of the orally-administered selective immunomodulator, SB 9200, in patients with chronic HBV. The initial cohort of the Phase 2a trial enrolled twenty (20) treatment-naïve chronic HBV patients without cirrhosis across multiple sites in Canada, Hong Kong and Korea.  Patients were randomized on a 4:1 basis and received either SB 9200 25mg or placebo daily for 12 weeks. The primary endpoints for the Phase 2a trial are safety and antiviral activity, as measured by the change in HBV DNA at week 12 from baseline, with multiple exploratory secondary endpoints. All patients in this cohort have transitioned to tenofovir disoproxil fumarate (marketed by Gilead Sciences, Inc. as Viread®) 300mg daily for an additional 12 weeks. “We are strongly encouraged by the safety profile of SB 9200 seen in this initial cohort of the Phase 2a trial and by the evidence of antiviral activity seen at the low dose of 25mg daily, because we studied the substantially higher doses of 200mg – 900mg daily for 7 days in our Phase 1 study in HCV patients,” stated Nezam Afdhal, M.D., D.Sc., Chief Medical Officer of Spring Bank Pharmaceuticals.  “The results from the initial cohort of the Phase 2a trial continue to support the development of SB 9200 as a potential treatment for chronic HBV to achieve the goal of a functional cure.  We have begun to rapidly enroll the second cohort (50 mg) of our Phase 2a trial and hope to report top-line results in the fourth quarter of 2017.” The initial cohort consisted of 11 HBeAg-positive and 9 HBeAg-negative patients, of which 80% were genotype B/C, the most common Asian genotypes. The overall safety profile of SB 9200 was favorable, and over the 12-week study, no serious adverse events were observed. Treatment-emergent adverse events ranged from mild to moderate in severity with no interferon-like side effects and were comparable to patients on placebo. There were no Grade 3 laboratory abnormalities, but alanine aminotransferase (ALT) flares, defined as an increase in ALT above 200 IU/ml, were observed in three patients. Two of these ALT flares were viral flares identified in patients on placebo and the other ALT flare was identified in one patient on SB 9200 at week 4, which was associated with a reduction in HBV DNA of 2.26 log and a 1.01 log reduction in HBsAg consistent with a beneficial immune flare. Study investigators did not observe any increase in bilirubin or evidence of hepatic decompensation. Overall, SB 9200 demonstrated a statistically significant reduction in HBV DNA at week 12 (unpaired t-test 2.85, p=0.01) compared to placebo, with a mean reduction of 0.6 log (range 0 to 1.87 log ) in the SB 9200 treatment group. For the secondary endpoint of quantitative HBsAg reduction, 5 of 16 patients (31%) in the SB 9200 treatment group had a greater than 0.5 log reduction at any time point (range 0.52 to 1.01 log ), compared to none in the placebo group. The 7 HBeAg-negative patients in the SB 9200 treatment group had the greatest mean reduction in HBV DNA at 0.9 log , and 3 of these 7 patients also had a greater than 0.5 log reduction in HBsAg. Professor Stephen Locarnini, the Principal Investigator of the Virology Core for the ACHIEVE trial and the Head, Research & Molecular Development, Victorian Infectious Diseases Reference Laboratory, stated, “Our virological studies from the first cohort showed antiviral activity of SB 9200 involving a novel immune and possibly direct antiviral mechanism targeting RIG-I, resulting in not only reduction in HBV DNA but also in HBsAg and HBV pgRNA as a surrogate for reduction in cccDNA.” Detailed results from the Phase 2a segment of the ACHIEVE study will be presented at a future medical conference. Spring Bank Pharmaceuticals will host a conference call at 8:00 a.m. ET tomorrow, Wednesday, May 24, 2017, to discuss top-line results of the initial cohort of the Phase 2a segment of the ACHIEVE study. The conference call may be accessed by dialing (866) 294-9216 for U.S. callers and (346) 406-0955 for international callers five minutes prior to the start of the call and providing the conference ID 27754723. Additionally, the live, listen-only webcast of the conference call can be accessed by visiting the Investors & Media section of the company’s website at www.springbankpharm.com. A replay of the conference call will be available following the call and may be accessed by visiting Spring Bank’s website. About SB 9200 and the ACHIEVE Study Spring Bank’s lead product candidate, SB 9200 is a novel small molecule nucleic acid hybrid (SMNH) compound being developed as both monotherapy and combination therapy for the treatment of chronic HBV.  The Phase 2a clinical trial is designed to enable Spring Bank to select one or two doses to move forward into a Phase 2b clinical trial and to obtain the necessary dosing and safety data to study the combined use of SB 9200 and a direct-acting antiviral. The first segment of the ACHIEVE trial is a Phase 2a placebo-controlled, sequential-cohort, double-blind trial to evaluate increasing doses of SB 9200 as monotherapy for 12 weeks followed by Viread® 300 mg for an additional 12 weeks.  The Phase 2a segment of the ACHIEVE trial has an adaptive trial design that will enroll 80 chronically-infected HBV patients between 18 and 70 years of age who have been or will be assigned to one of four dosing cohorts, 25 mg, 50 mg, 100 mg or 200 mg of SB 9200, or placebo, once daily for 12 weeks. All subjects will then receive Viread® 300 mg once daily for an additional 12 weeks of treatment. The Phase 2b segment of the ACHIEVE trial is planned to examine the concomitant use of SB 9200 and Viread® in approximately 200 HBV patients. Subject to the results of the Phase 2a clinical trial and obtaining additional funding, Spring Bank plans to initiate the Phase 2b segment of the ACHIEVE trial in 2018. 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 (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, including hepatitis B virus (HBV). 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 Pharmaceuticals is also developing other SMNH product candidates, including SB 11285, the company’s lead immunotherapeutic agent for the treatment of selected cancers through the activation of the STimulator of INterferon Genes, or STING, pathway. For more information, please visit www.springbankpharm.com Statements in this press release about Spring Bank’s future expectations, plans and prospects, including, but not limited to, statements about the company’s expectations for the enrollment of patients in the second cohort of the Phase 2a segment of the ACHIEVE trial; the company’s anticipated timeline for disclosing top-line results from the second cohort of the Phase 2a segment of the ACHIEVE trial and the company’s anticipated timeline for initiating the Phase 2b segment of the ACHIEVE trial, as well as any other statements regarding matters that are not historical facts, may constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including whether Spring Bank’s cash resources will be sufficient to fund its continuing operations for the periods and/or trials anticipated; whether results obtained in preclinical studies and clinical trials will be indicative of results obtained in future clinical trials; whether Spring Bank’s product candidates will advance through the clinical trial process on a timely basis, or at all; whether the results of such trials will warrant submission for approval from the United States Food and Drug Administration or equivalent foreign regulatory agencies; whether Spring Bank’s product candidates will receive approval from regulatory agencies on a timely basis or at all; whether, if product candidates obtain approval, they will be successfully distributed and marketed; and other factors discussed in the "Risk Factors" section of Spring Bank’s Annual Report on Form 10-K for the year ended December 31, 2016, which was filed with the Securities and Exchange Commission (SEC) on February 14, 2017, and in other filings Spring Bank makes with the SEC from time to time. In addition, the forward-looking statements included in this press release represent Spring Bank’s views as of the date hereof. Spring Bank anticipates that subsequent events and developments will cause Spring Bank’s views to change. However, while Spring Bank may elect to update these forward-looking statements at some point in the future, Spring Bank specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Spring Bank’s views as of any date subsequent to the date hereof.


SB 9200 Shows Favorable Safety Profile and Significant Antiviral Activity Against HBV DNA and HBsAg with Initial Low Dose Monotherapy of 25mg Conference Call Scheduled for Tomorrow, May 24th at 8:00 a.m. ET HOPKINTON, Mass., May 23, 2017 (GLOBE NEWSWIRE) -- Spring Bank Pharmaceuticals, Inc. (Nasdaq:SBPH) announced today the top-line results from the 25mg monotherapy cohort of the Phase 2a segment of the ACHIEVE study, a global, placebo-controlled, sequential-cohort, double-blind Phase 2 clinical trial, focused on the safety and antiviral activity of the orally-administered selective immunomodulator, SB 9200, in patients with chronic HBV. The initial cohort of the Phase 2a trial enrolled twenty (20) treatment-naïve chronic HBV patients without cirrhosis across multiple sites in Canada, Hong Kong and Korea.  Patients were randomized on a 4:1 basis and received either SB 9200 25mg or placebo daily for 12 weeks. The primary endpoints for the Phase 2a trial are safety and antiviral activity, as measured by the change in HBV DNA at week 12 from baseline, with multiple exploratory secondary endpoints. All patients in this cohort have transitioned to tenofovir disoproxil fumarate (marketed by Gilead Sciences, Inc. as Viread®) 300mg daily for an additional 12 weeks. “We are strongly encouraged by the safety profile of SB 9200 seen in this initial cohort of the Phase 2a trial and by the evidence of antiviral activity seen at the low dose of 25mg daily, because we studied the substantially higher doses of 200mg – 900mg daily for 7 days in our Phase 1 study in HCV patients,” stated Nezam Afdhal, M.D., D.Sc., Chief Medical Officer of Spring Bank Pharmaceuticals.  “The results from the initial cohort of the Phase 2a trial continue to support the development of SB 9200 as a potential treatment for chronic HBV to achieve the goal of a functional cure.  We have begun to rapidly enroll the second cohort (50 mg) of our Phase 2a trial and hope to report top-line results in the fourth quarter of 2017.” The initial cohort consisted of 11 HBeAg-positive and 9 HBeAg-negative patients, of which 80% were genotype B/C, the most common Asian genotypes. The overall safety profile of SB 9200 was favorable, and over the 12-week study, no serious adverse events were observed. Treatment-emergent adverse events ranged from mild to moderate in severity with no interferon-like side effects and were comparable to patients on placebo. There were no Grade 3 laboratory abnormalities, but alanine aminotransferase (ALT) flares, defined as an increase in ALT above 200 IU/ml, were observed in three patients. Two of these ALT flares were viral flares identified in patients on placebo and the other ALT flare was identified in one patient on SB 9200 at week 4, which was associated with a reduction in HBV DNA of 2.26 log and a 1.01 log reduction in HBsAg consistent with a beneficial immune flare. Study investigators did not observe any increase in bilirubin or evidence of hepatic decompensation. Overall, SB 9200 demonstrated a statistically significant reduction in HBV DNA at week 12 (unpaired t-test 2.85, p=0.01) compared to placebo, with a mean reduction of 0.6 log (range 0 to 1.87 log ) in the SB 9200 treatment group. For the secondary endpoint of quantitative HBsAg reduction, 5 of 16 patients (31%) in the SB 9200 treatment group had a greater than 0.5 log reduction at any time point (range 0.52 to 1.01 log ), compared to none in the placebo group. The 7 HBeAg-negative patients in the SB 9200 treatment group had the greatest mean reduction in HBV DNA at 0.9 log , and 3 of these 7 patients also had a greater than 0.5 log reduction in HBsAg. Professor Stephen Locarnini, the Principal Investigator of the Virology Core for the ACHIEVE trial and the Head, Research & Molecular Development, Victorian Infectious Diseases Reference Laboratory, stated, “Our virological studies from the first cohort showed antiviral activity of SB 9200 involving a novel immune and possibly direct antiviral mechanism targeting RIG-I, resulting in not only reduction in HBV DNA but also in HBsAg and HBV pgRNA as a surrogate for reduction in cccDNA.” Detailed results from the Phase 2a segment of the ACHIEVE study will be presented at a future medical conference. Spring Bank Pharmaceuticals will host a conference call at 8:00 a.m. ET tomorrow, Wednesday, May 24, 2017, to discuss top-line results of the initial cohort of the Phase 2a segment of the ACHIEVE study. The conference call may be accessed by dialing (866) 294-9216 for U.S. callers and (346) 406-0955 for international callers five minutes prior to the start of the call and providing the conference ID 27754723. Additionally, the live, listen-only webcast of the conference call can be accessed by visiting the Investors & Media section of the company’s website at www.springbankpharm.com. A replay of the conference call will be available following the call and may be accessed by visiting Spring Bank’s website. About SB 9200 and the ACHIEVE Study Spring Bank’s lead product candidate, SB 9200 is a novel small molecule nucleic acid hybrid (SMNH) compound being developed as both monotherapy and combination therapy for the treatment of chronic HBV.  The Phase 2a clinical trial is designed to enable Spring Bank to select one or two doses to move forward into a Phase 2b clinical trial and to obtain the necessary dosing and safety data to study the combined use of SB 9200 and a direct-acting antiviral. The first segment of the ACHIEVE trial is a Phase 2a placebo-controlled, sequential-cohort, double-blind trial to evaluate increasing doses of SB 9200 as monotherapy for 12 weeks followed by Viread® 300 mg for an additional 12 weeks.  The Phase 2a segment of the ACHIEVE trial has an adaptive trial design that will enroll 80 chronically-infected HBV patients between 18 and 70 years of age who have been or will be assigned to one of four dosing cohorts, 25 mg, 50 mg, 100 mg or 200 mg of SB 9200, or placebo, once daily for 12 weeks. All subjects will then receive Viread® 300 mg once daily for an additional 12 weeks of treatment. The Phase 2b segment of the ACHIEVE trial is planned to examine the concomitant use of SB 9200 and Viread® in approximately 200 HBV patients. Subject to the results of the Phase 2a clinical trial and obtaining additional funding, Spring Bank plans to initiate the Phase 2b segment of the ACHIEVE trial in 2018. 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 (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, including hepatitis B virus (HBV). 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 Pharmaceuticals is also developing other SMNH product candidates, including SB 11285, the company’s lead immunotherapeutic agent for the treatment of selected cancers through the activation of the STimulator of INterferon Genes, or STING, pathway. For more information, please visit www.springbankpharm.com Statements in this press release about Spring Bank’s future expectations, plans and prospects, including, but not limited to, statements about the company’s expectations for the enrollment of patients in the second cohort of the Phase 2a segment of the ACHIEVE trial; the company’s anticipated timeline for disclosing top-line results from the second cohort of the Phase 2a segment of the ACHIEVE trial and the company’s anticipated timeline for initiating the Phase 2b segment of the ACHIEVE trial, as well as any other statements regarding matters that are not historical facts, may constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including whether Spring Bank’s cash resources will be sufficient to fund its continuing operations for the periods and/or trials anticipated; whether results obtained in preclinical studies and clinical trials will be indicative of results obtained in future clinical trials; whether Spring Bank’s product candidates will advance through the clinical trial process on a timely basis, or at all; whether the results of such trials will warrant submission for approval from the United States Food and Drug Administration or equivalent foreign regulatory agencies; whether Spring Bank’s product candidates will receive approval from regulatory agencies on a timely basis or at all; whether, if product candidates obtain approval, they will be successfully distributed and marketed; and other factors discussed in the "Risk Factors" section of Spring Bank’s Annual Report on Form 10-K for the year ended December 31, 2016, which was filed with the Securities and Exchange Commission (SEC) on February 14, 2017, and in other filings Spring Bank makes with the SEC from time to time. In addition, the forward-looking statements included in this press release represent Spring Bank’s views as of the date hereof. Spring Bank anticipates that subsequent events and developments will cause Spring Bank’s views to change. However, while Spring Bank may elect to update these forward-looking statements at some point in the future, Spring Bank specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Spring Bank’s views as of any date subsequent to the date hereof.


Dandri M.,University of Hamburg | Locarnini S.,Victorian Infectious Diseases Reference Laboratory
Gut | Year: 2012

Chronic hepatitis B virus (HBV) infection remains a major health burden and the main risk factor for the development of hepatocellular carcinoma worldwide. However, HBV is not directly cytopathic and liver injury appears to be mostly caused by repeated attempts of the host's immune responses to control the infection. Recent studies have shown that the unique replication strategy adopted by HBV enables it to survive within the infected hepatocyte while complex virus-host interplays ensure the virus is able to fulfil its replication requirements yet is still able to evade important host antiviral innate immune responses. Clearer understanding of the host and viral mechanisms affecting HBV replication and persistence is necessary to design more effective therapeutic strategies aimed at improving the management of patients with chronic HBV infection to eventually achieve viral eradication. This article focuses on summarising the current knowledge of factors influencing the course of HBV infection, giving emphasis on the use of novel assays and quantitative serological and intrahepatic biomarkers as tools for predicting treatment response and disease progression.


Revill P.,Victorian Infectious Diseases Reference Laboratory | Yuan Z.,Fudan University
Antiviral Therapy | Year: 2013

The mechanisms by which HBV establishes and maintains chronic infection are poorly understood. Although adult acquired HBV is generally cleared by a robust immune response, most individuals infected at childbirth or in very early childhood develop lifelong chronic infection. In addition, acute infections are unresolved in approximately 5% of individuals infected in adulthood. The host cell mechanisms that ensure establishment and resolution of acute infection and persistent infection remain unclear. Currently, two schools of thought suggest that either HBV is a 'stealth' virus, which initially establishes infection by avoiding host innate immune responses, or that HBV facilitates initial infection and progression to persistence by actively manipulating the host innate immune response to its advantage. There is increasing evidence that activation of innate host cell signalling pathways plays a major role in limiting adult acquired HBV infection and that, in turn, HBV has evolved numerous strategies to counteract these defence mechanisms. In this review, we summarize current knowledge regarding innate immune responses to HBV infection and discuss how HBV regulates cell signalling pathways to its advantage, particularly in the setting of chronic HBV infection. In turn, we show how an intimate knowledge of innate immune responses is driving development of novel therapeutic agents to treat chronic HBV infection. © 2013 International Medical Press.


Zoulim F.,University of Lyon | Locarnini S.,Victorian Infectious Diseases Reference Laboratory
Liver International | Year: 2013

The management of treatment failure in patients with chronic hepatitis B, remains a clinical concern. Incomplete viral suppression and the emergence of drug resistance are key determinants of treatment failure. The correct choice of a potent first-line therapy to achieve sustained long-term suppression of viral replication provides the best chance of preventing treatment failure and drug resistance. Clinical studies have demonstrated that drugs with a high barrier to resistance have significantly lower rates of resistance compared with those with a low barrier to resistance. Management of treatment failure requires precise clinical and virological monitoring as well as early treatment intervention with appropriate noncross-resistant antivirals. Long-term surveillance of treatment efficacy and possible emergence of drug resistance is necessary in patients who have been sequentially treated with multiple antivirals. The identification of novel treatment targets remains a major research goal to improve the efficacy of current antiviral therapy through combination therapy regimens. © 2012 John Wiley & Sons A/S.


Marshall J.A.,Victorian Infectious Diseases Reference Laboratory
International journal of environmental research and public health | Year: 2011

Noroviruses are a major cause of gastroenteritis outbreaks worldwide. Norovirus outbreaks frequently occur as epidemics which appear to be related to both genetic and environmental factors. This review considers recent progress in understanding these factors. The norovirus genome undergoes continuous change and this appears to be important in the persistence of the virus in the community. Studies on the common GII.4 genotype have shown that some norovirus outbreak epidemics involving this genotype are correlated with specific changes in the genome. In contrast to the growing understanding of the role of genetic factors in norovirus outbreak epidemics, the role of environmental factors is less well understood. Topics reviewed here include long term excretion of norovirus in some individuals, long term survivability of norovirus in the environment, the role of meteorological factors in the control of norovirus outbreaks and the possible zoonotic transmission of the virus.


Locarnini S.,Victorian Infectious Diseases Reference Laboratory
Journal of Hepatology | Year: 2011

Recent advances in molecular biology have led to the development of novel small molecules that target specific viral proteins of the hepatitis C virus (HCV) life cycle. These drugs, collectively termed directly acting antivirals (DAA) against HCV, include a range of non-structural (NS) 3/NS4A protease, NS5B polymerase, and NS5A inhibitors at various stages of clinical development. The rapid replication rate of HCV, along with the low fidelity of its polymerase, gives rise to generations of mutations throughout the viral genome resulting in remarkable sequence variation in the HCV population, known as a quasispecies. The efficacy of DAAs is limited by the presence of those mutations that give rise to amino-acid substitutions within the targeted protein, and that affect the viral sensitivity to these compounds. Thus, due to the high genetic variability of HCV, variants with reduced susceptibility to DAA can occur naturally even before treatment begins, but usually at low levels. Not surprisingly then, these changes are selected in patients either breaking through or not responding to potent DAA treatment. In vitro or in vivo, six major position mutations in the NS3 HCV protease (36, 54, 155, 156, 168, and 170) have now been reported associated with different levels of resistance. The amino acid composition at several of the drug resistance sites can vary between the HCV genotypes/subtypes, resulting in different consensus amino acids leading to a reduction in replicative fitness as well as reduced DAA sensitivity. Different amino acid diversity profiles for HCV genotypes/subtypes suggest differences in the position/type of immune escape and drug resistance mutations. Also, different pathways of resistance profiles based on the chemical scaffold (linear or macrocyclic) of the protease inhibitors have been described. This review first describes how resistance to a protease inhibitor can develop and then provides an overview of the mechanism of how particular mutations confer varying levels of resistance to protease inhibitor, which have been identified and characterized using both genotypic and phenotypic tools. Future potential therapeutic strategies to assist patients who do develop resistance to protease inhibitors are also outlined. The challenge developing new HCV protease inhibitors should take into consideration not only the antiviral potency of the drugs, the occurrence and importance of side effects, the frequency of oral administration, but also the resistance profiles of these agents. © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

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