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Spring Bank Announces Positive Study Results from the Inarigivir ACHIEVE Trial
- Maximum Reduction in HBV DNA up to 2.76log10 and HBV RNA up to 5.0log10
- 28% of Inarigivir Treated Patients Demonstrate a HBsAg Response with a Mean Reduction of 0.8log10 and a Maximum Reduction of 1.4log10 in Cohorts 1-3 of ACHIEVE Trial
- Two Additional Cohorts Added to HBV Clinical Program for Inarigivir Co-Administered with Gilead’s Tenofovir Alafenamide
- Inarigivir Clinical Program Accelerated to Enter Multiple Global Phase 2b/3 Trials in Early 2019
HOPKINTON, Mass., Aug. 02, 2018 (GLOBE NEWSWIRE) -- Spring Bank Pharmaceuticals, Inc. (Nasdaq: SBPH) today announced positive results from the third cohort (inarigivir 100mg) of Part A of the ongoing Phase 2 ACHIEVE trial. Spring Bank also announced the expansion of the Phase 2 clinical trial being undertaken by Gilead Sciences, Inc. to include up to two additional cohorts of inarigivir co-administered with tenofovir alafenamide 25mg in chronic hepatitis B patients.
Spring Bank is developing inarigivir, an orally-administered investigational selective immunomodulator, as a potential backbone in a combinatorial treatment for chronic hepatitis B virus (HBV), with a goal to accelerate and substantially increase functional cure rates in a simple, safe and selective manner. Spring Bank has already randomized the majority of the patients in the fourth and final cohort (inarigivir 200mg) of the ACHIEVE trial and anticipates that it will have top-line results by the end of 2018.
In the third cohort, 20 patients were randomized; 17 on inarigivir 100mg (13 HBeAg-positive, 4 HBeAg-negative) and 3 on placebo. The primary endpoints, safety and antiviral activity, were achieved at both week 12 (inarigivir monotherapy) and week 24 (following the switch to tenofovir disoproxil fumarate (TDF) 300mg after week 12). Inarigivir was well-tolerated with no serious adverse events observed. Overall, treatment-emergent adverse events ranged from mild to moderate in severity, with no observed interferon-like side effects or clinical or biochemical events above Grade 3. One HBeAg-negative patient on inarigivir alone had an ALT flare >200 IU with reductions in HBV DNA and HBsAg consistent with previously described inarigivir immune flares. Overall, mean HBV DNA reduction at week 12 was 1.0log10, with a mean 0.55log10 reduction in HBeAg-positive patients and a mean 2.26log10 reduction in HBeAg-negative patients, which was significantly superior (t-test: p=0.006) to combined placebo from all groups (n=11). Similar log reductions were seen for the secondary endpoint of HBV RNA reduction, with a mean 0.6log10 reduction in HBeAg-positive patients and a mean 1.4log10 reduction in HBeAg-negative patients. Three patients had a greater than 0.5log10 reduction in HBsAg at either week 12 or week 24. Overall, 13 of 47 (28%) of inarigivir-treated patients in the ACHIEVE trial have had a predefined HBsAg response of 0.5log10 decrease, with a mean decrease in the responder group of 0.8log10 (range 0.5 – 1.4log10) at either week 12 or week 24 after the switch to TDF. Baseline HBsAg level < 10,000 IU (4log10) remains the strongest predictor of response to inarigivir across all cohorts for HBV DNA and HBV RNA reductions irrespective of HBeAg status. This response is consistent with the known role of HBsAg as a down regulator of the host immune response to HBV. Detailed results from this third cohort will be presented at a future medical conference.
“We are excited to see the continued efficacious dose response and the favorable safety profile of inarigivir, including no interferon-like side effects. We are particularly pleased to see a maximum reduction in both HBV DNA and HBV RNA by up to 2.76log10 and 5.0log10, respectively, in this third cohort,” stated Nezam Afdhal, M.D., D.Sc., chief medical officer of Spring Bank Pharmaceuticals. “Overall, inarigivir responses have been proportional to the baseline HBsAg level and are reflective of the mechanism of action of inarigivir as an immunomodulator. Moreover, the combined 28% response rate in HBsAg reduction demonstrated by inarigivir in the first three cohorts of the ACHIEVE trial is superior to both interferon and any oral HBV antiviral agent known to be under development.”
The investigation of inarigivir in combination with tenofovir alafenamide for naïve chronic HBV patients continues in a Phase 2 clinical study being conducted by Gilead. The new second cohort of the study will assess 200mg inarigivir co-adminstered with tenofovir alafenamide, subject to independent regulator assessments of the safety of inarigivir at the 200mg dose. Additionally, a new third cohort has been added to examine the administration of inarigivir 100mg in chronic HBV patients currently treated with nucleoside/tide analogues (a “Nuc-suppressed” population).
The expansion of the inarigivir + tenofovir alafenamide co-administration program allows Spring Bank to conclude the ACHIEVE trial when the fourth cohort (200mg) of Part A is completed. This expansion means that the planned Part B of the ACHIEVE trial evaluating inarigivir with tenofovir disoproxil 300mg is no longer necessary. More importantly, this expansion allows Spring Bank to advance the inarigivir development program into multiple planned Phase 2b/3 programs in early 2019. Planned clinical trials include: 1) inarigivir monotherapy as an add-on to Nuc-suppressed patients (“Suppress and Shock”) and 2) patients who stop Nuc therapy (“Stop and Shock”). In addition to advancing inarigivir into a Phase 2b/3 program, Spring Bank plans to initiate a Phase 2b trial with SB 9225, the investigational fixed-dose combination of inarigivir and tenofovir disoproxil fumarate, for treatment-naïve HBV patients.
Spring Bank also continues to explore collaborations, including with siRNA compounds targeting HBsAg, as well as other antiviral and immunomodulatory mechanisms, which reflect the potential of inarigivir as a potential backbone in a combinatorial treatment for chronic HBV. Spring Bank anticipates inarigivir will be included in a “triple combination” clinical trial with an siRNA compound or a different mechanism in the first half of 2019.
Dr. Afdhal continued, “We are happy to expand our clinical trial collaboration with our partners at Gilead. HBV cure will require multiple, innovative therapies, and we are excited that inarigivir is part of a development strategy with Gilead.”
Spring Bank will host a conference call and webcast at 8:00 a.m. EST to provide a corporate update and discuss the third cohort. The conference call may be accessed by dialing 800-289-0438 for U.S. callers and 323-794-2423 for international callers and providing the conference ID 9011622. A 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 until August 16, 2018, or by dialing 844-512-2921 for U.S. callers and 412-317-6671 for international callers five minutes prior to the start of the call and providing the conference ID 9011622. A replay of the call may be accessed by visiting Spring Bank’s website.
About Inarigivir and the ACHIEVE Trial
Spring Bank’s lead product candidate, inarigivir is a novel small molecule nucleic acid hybrid (SMNH) compound being developed as both monotherapy and combination therapy for the treatment of chronic HBV. Part A of the Phase 2 ACHIEVE trial is a placebo-controlled, sequential-cohort, double-blind trial to evaluate increasing doses of inarigivir as monotherapy for 12 weeks followed by Viread® 300mg for an additional 12 weeks. Part A 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, 25mg, 50mg, 100mg or 200mg of inarigivir, or placebo, once daily for 12 weeks. All subjects then receive Viread® 300mg once daily for an additional 12 weeks of treatment.
About Spring Bank Pharmaceuticals
Spring Bank Pharmaceuticals, Inc. 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, inarigivir soproxil (formerly SB 9200) for the treatment of viral diseases, including hepatitis B virus (HBV). 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, 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. These statements include, but are not limited to, statements about (i) the anticipated timing of announcing top-line results from the monotherapy segment of the fourth cohort of the ACHIEVE trial; (ii) the anticipated design, initiation and completion of up to two additional cohorts in the Phase 2 combination study being conducted by Gilead; (iii) the elimination of Part B of Spring Bank’s ACHIEVE trial; (iv) the timing and implementation of Spring Bank’s inarigivir development program, including the Phase 2b/3 trials planned for 2019; and (v) the inclusion of inarigivir in a “triple combination” clinical trial with an siRNA compound or a different mechanism in 2019.
Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including whether results obtained in preclinical studies and clinical trials will be indicative of results obtained in future clinical trials, including any results announced to date from Part A of the ACHIEVE Phase 2 trial; whether Spring Bank’s product candidates will advance through the clinical trial process on a timely basis, or at all; whether Spring Bank’s cash resources will be sufficient to fund its continuing operations for the periods and/or trials anticipated; 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, 2017, which was filed with the Securities and Exchange Commission (SEC) on February 20, 2018, Spring Bank's Quarterly Reports on Form 10-Q that have been filed with the SEC, 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.
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