UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 OR 15(d) of The Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): March 26, 2020
Arbutus Biopharma Corporation
(Exact name of registrant as specified in charter)
British Columbia, Canada | 001-34949 | 98-0597776 | ||
(State or other jurisdiction of incorporation) | (Commission File Number) | (IRS Employer Identification No.) | ||
701 Veterans Circle Warminster, Pennsylvania | 18974 | |
(Address of principal executive offices) | (Zip Code) | |
(267) 469-0914
Registrant’s telephone number, including area code
(Former name or former address, if changed since last report.)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
o | Written communication pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
o | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
o | Pre-commencement communication pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
o | Pre-commencement communication pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Securities registered pursuant to Section 12(b) of the Act:
Title of each class | Trading Symbol(s) | Name of each exchange on which registered | ||
Common Shares, without par value | ABUS | The Nasdaq Stock Market LLC | ||
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company o
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. o
Item 8.01. Other Events.
On March 26, 2020, Arbutus Biopharma Corporation (the "Company") issued a press release announcing positive preliminary Phase 1a/1b clinical trial results for AB-729, a proprietary GalNAc delivered RNAi compound in development for patients with chronic hepatitis B. A copy of the press release is filed herewith as Exhibit 99.1 and is incorporated by reference herein.
Also on March 26, 2020, the Company held a conference call and webcast presentation to discuss the preliminary Phase 1a/1b trial results for AB-729. A copy of the presentation is filed herewith as Exhibit 99.2 and is incorporated by reference herein.
Item 9.01. Financial Statements and Exhibits.
(d) Exhibits.
Exhibit Number | Description | |
99.1 | ||
99.2 | ||
SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
Arbutus Biopharma Corporation | ||
Date: March 26, 2020 | By: | /s/ David C. Hastings |
Name: | David C. Hastings | |
Title: | Chief Financial Officer | |
 | Exhibit 99.1 | |
Arbutus Announces Positive Preliminary Phase 1a/1b Clinical Trial Results for
AB-729, a Proprietary GalNAc Delivered RNAi Compound in Development for
People Living with Chronic Hepatitis B
Positive single dose AB-729 data in chronic hepatitis B subjects supports
further clinical development
First multiple dose cohort results expected in second half of 2020
One or more additional single dose cohorts planned to further optimize antiviral response and dosing frequency with results expected in the second half of 2020
Conference call and webcast scheduled today at 4:30 PM ET
March 26, 2020
Warminster, PA - Arbutus Biopharma Corporation (Nasdaq: ABUS), a Hepatitis B Virus (HBV) therapeutic solutions company, today announced positive preliminary results from a Phase 1a/1b clinical trial (AB-729-001) in healthy subjects and two cohorts of chronic hepatitis B subjects on nucleos(t)ide antiviral therapy, all of whom received a single subcutaneous injection of AB-729. AB-729-001 is an ongoing Phase 1a/1b clinical trial designed to determine the most effective dose and dosing interval for use in future Phase 2 combination clinical trials.
William Collier, President and Chief Executive Officer of Arbutus, stated, “These encouraging preliminary results demonstrate that AB-729 is a potent RNAi agent capable of reducing HBsAg plasma levels and support its further development as a treatment for people living with chronic hepatitis B. Our plan is to move forward into the multiple dose portion of the clinical trial with the 60 mg dose and, in parallel, to explore additional single dose cohorts beginning with the 90 mg dose. We intend to initiate these cohorts as soon as possible; however, at this point, it is not possible to predict if the COVID-19 pandemic will negatively impact our plans and timelines. Provided we can execute our clinical trials as planned, we continue to expect these data sets in the second half of the year."
Mean HBsAg changes from baseline:
60 mg Cohort (N=6) | 180 mg Cohort (N=4) | |
Day 29 mean log10 IU/mL (SE) | -0.24# (0.13) | -0.81* (0.38) |
Week 12 mean log10 IU/mL (SE) | NA | -0.98 (0.22) |
#In the 60 mg cohort, the maximum Day 29 decline was -0.62 log10.
*In the 180 mg cohort, excluding one subject with a HBsAg decline of -1.94 log10, the mean (SE) reduction for the remaining 3 subjects was -0.44 log10 (0.07) at Day 29 and -0.77 log10 (0.06) at Week 12.
| Exhibit 99.1 | |
Dr. Gaston Picchio, Chief Development Officer of Arbutus, stated, “AB-729 dosed at either 60 mg or 180 mg in chronic hepatitis B subjects was generally safe and well tolerated and resulted in meaningful reductions in HBsAg levels. Additionally, after a single 180 mg dose, HBsAg levels continued to decline well beyond Week 12, suggesting that AB-729 has the potential to be dosed less frequently than every four weeks.”
Dr. Picchio added, “The subject receiving the 180 mg dose who experienced the highest HBsAg decline also experienced a Grade 3 ALT/AST flare. While the flare may have been related to an acute gastroenteritis and self-medication, we believe evaluating at least one additional single dose cohort starting at 90 mg is appropriate and should allow us to determine if a mid-dose would provide the greatest benefit in terms of safety, efficacy and dosing interval.”
Preliminary safety summary in healthy subjects
• | In the 60 mg, 180 mg and 360 mg cohorts, no serious adverse events (SAEs) were observed; most adverse events (AEs) were mild (13/15) and considered unrelated (12/15) to AB-729. |
• | Two subjects in the 360 mg cohort had asymptomatic, reversible Grade 3 ALT elevations assessed as related to AB-729. Neither subject had meaningful changes in any other laboratory parameter excepting Grade 1 or 2 AST elevation. |
• | There were no other clinically relevant abnormalities in laboratory tests, ECGs, or vital signs. |
Preliminary safety and efficacy summary in chronic HBV subjects
• | HBsAg declines were observed in all 4 subjects (3 HBeAg negative, 1 HBeAg positive) in the 180 mg cohort, with a mean HBsAg (SE) log10 reduction of -0.81 (0.38) at Week 4 and -0.98 (0.22) at Week 12. |
• | In the 180 mg cohort, maximum HBsAg decline of -1.94 log10 occurred at Week 4 in one subject (HBeAg negative). HBsAg declines continued beyond Week 12 for 2/3 subjects in the 180 mg cohort with available data, exceeding -1.00 log10 in both subjects. A 4th subject in the 180 mg cohort had continuous HBsAg decline up to 12 weeks post-dose, with a maximum decline of -0.73 log10 at Week 12 (the last available time point). |
• | Mean log10 (SE) HBsAg decline in the 6 subjects in the 60 mg cohort (all HBeAg negative) was -0.24 (0.13) at Day 29. The maximum HBsAg decline in this cohort was -0.62 log10 at Day 29. Subjects in the 60 mg cohort will continue to be followed for twelve weeks. At this time only the four week data are available for the 60 mg cohort. |
• | In chronic hepatitis B subjects administered 180 mg (N=4) or 60 mg (N=6) of AB-729 there were no SAEs. In the 180 mg cohort, 8 AEs were observed and included asymptomatic, transient Grade 1 ALT/AST in 1 subject, Grade 1 ALT only in 1 subject, and 1 subject with Grade 1 ALT /AST at baseline who experienced unrelated gastroenteritis and self-medicated associated with transient Grade 3 ALT/AST |
| Exhibit 99.1 | |
elevations. In the 60 mg cohort, 2 AEs were observed, and all subjects had normal ALT/AST levels.
Summary of clinical trial design
Study AB-729-001 is an ongoing first-in-human clinical trial of AB-729 consisting of three parts:
• | In Part 1, 3 cohorts of healthy subjects were randomized 4:2 to receive single doses (60mg, 180mg or 360mg) of AB-729 or placebo. |
• | In Part 2, non-cirrhotic, HBeAg positive or negative, chronic hepatitis B subjects (N=6) currently taking nucleos(t)ide antiviral therapy with HBV DNA below the limit of quantitation received single doses (60mg or 180mg) of AB-729. All subjects continued their nucleos(t)ide antiviral therapy throughout the trial. Part 2 is designed to include dosing of AB-729 in HBV DNA positive chronic hepatitis B subjects. |
• | In Part 3, chronic hepatitis B subjects, HBV DNA negative first and HBV DNA positive later, will receive multiple doses of AB-729 for up to six months. |
COVID-19
In December 2019 an outbreak of a novel strain of coronavirus (COVID-19) was identified in Wuhan, China. This virus continues to spread globally, has been declared a pandemic by the World Health Organization and has spread to nearly every country in the world. The impact of this pandemic has been, and will likely continue to be, extensive in many aspects of society. The pandemic has resulted in and will likely continue to result in significant disruptions to businesses. A number of countries and other jurisdictions around the world have implemented extreme measures to try and slow the spread of the virus. These measures include the closing of businesses and requiring people to stay in their homes, the latter of which raises uncertainty regarding the ability to travel to hospitals in order to participate in clinical trials. Additional measures that have had, and will likely continue to have, a major impact on clinical development, at least in the near-term, include shortages and delays in the supply chain, and prohibitions in certain countries on enrolling subjects in new clinical trials (e.g. in Australia). It is not possible to predict if the COVID-19 pandemic will negatively impact our plans and timelines.
About AB-729
AB-729 is a RNA interference (RNAi) therapeutic targeted to hepatocytes using Arbutus’ novel covalently conjugated N-acetylgalactosamine (GalNAc) delivery technology that enables subcutaneous delivery. AB-729 inhibits viral replication and reduces all HBV antigens, including hepatitis B surface antigen in preclinical models. Reducing hepatitis B surface antigen is thought to be a key prerequisite to enable reawakening of a patient’s immune system to respond to the virus.
| Exhibit 99.1 | |
Conference Call and Webcast Today
Arbutus will hold a conference call and live webcast today, March 26, 2020 at 4:30 PM Eastern Time, to discuss the preliminary Phase 1a/1b clinical trial results for AB-729. You can access the live webcast, which will include presentation slides, through the Investors section of Arbutus' website at www.arbutusbio.com or directly at Live Webcast. Alternatively, please dial (866) 393 - 1607 or (914) 495 - 8556 and reference conference ID 2169859.
An archived webcast will be available on the Arbutus website after the event.
About Arbutus
Arbutus Biopharma Corporation is a publicly-traded (Nasdaq: ABUS) biopharmaceutical company dedicated to discovering, developing, and commercializing a cure for patients suffering from chronic hepatitis B (HBV) infection. Arbutus is developing multiple drug candidates, each of which have the potential to improve upon the standard of care and contribute to a curative combination regimen. For more information, visit www.arbutusbio.com.
Forward-Looking Statements and Information
This press release contains forward-looking statements within the meaning of the Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, and forward-looking information within the meaning of Canadian securities laws (collectively, “forward-looking statements”). Forward-looking statements in this press release include statements about our expectations regarding the timing and clinical development of our product candidates, including the evaluation of multiple dose and additional single-dose cohorts in our Phase 1a/1b clinical trial for AB-729 during 2020; and the potential for our drug candidates to improve upon the standard of care and contribute to a curative combination regimen for chronic HBV.
With respect to the forward-looking statements contained in this press release, Arbutus has made numerous assumptions regarding, among other things: the effectiveness and timeliness of preclinical studies and clinical trials, and the usefulness of the data; the timeliness of regulatory approvals; the continued demand for Arbutus’ assets; and the stability of economic and market conditions. While Arbutus considers these assumptions to be reasonable, these assumptions are inherently subject to significant business, economic, competitive, market and social uncertainties and contingencies, including uncertainties and contingencies related to the ongoing COVID-19 pandemic.
Additionally, there are known and unknown risk factors which could cause Arbutus’ actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or
| Exhibit 99.1 | |
implied by the forward-looking statements contained herein. Known risk factors include, among others: anticipated pre-clinical studies and clinical trials may be more costly or take longer to complete than anticipated, and may never be initiated or completed, or may not generate results that warrant future development of the tested drug candidate; changes in Arbutus’ strategy regarding its product candidates and clinical development activities; Arbutus may not receive the necessary regulatory approvals for the clinical development of Arbutus’ products; economic and market conditions may worsen; market shifts may require a change in strategic focus; and the ongoing COVID-19 pandemic could significantly disrupt our clinical development programs.
A more complete discussion of the risks and uncertainties facing Arbutus appears in Arbutus’ Annual Report on Form 10-K, Arbutus’ Quarterly Reports on Form 10-Q and Arbutus’ continuous and periodic disclosure filings, which are available at www.sedar.com and at www.sec.gov. All forward-looking statements herein are qualified in their entirety by this cautionary statement, and Arbutus disclaims any obligation to revise or update any such forward-looking statements or to publicly announce the result of any revisions to any of the forward-looking statements contained herein to reflect future results, events or developments, except as required by law.
Contact Information
Investors and Media
William H. Collier
President and CEO
Phone: 604-419-3200
Email: ir@arbutusbio.com
Pam Murphy
Investor Relations Consultant
Phone: 604-419-3200
Email: ir@arbutusbio.com
AB-729-001 Preliminary Results March 26, 2020 NASDAQ: ABUS www.arbutusbio.com
Forward Looking Statements This presentation contains forward-looking statements within the meaning of the Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, and forward- looking information within the meaning of Canadian securities laws (collectively, “forward-looking statements”). Forward-looking statements in this presentation include statements about our expectations regarding the timing and clinical development of our product candidates, including the evaluation of multiple dose and additional single-dose cohorts in our Phase 1a/1b clinical trial for AB-729 during 2020; and the potential for our drug candidates to improve upon the standard of care and contribute to a curative combination regimen for chronic HBV. With respect to the forward-looking statements contained in this presentation, Arbutus has made numerous assumptions regarding, among other things: the effectiveness and timeliness of preclinical studies and clinical trials, and the usefulness of the data; the timeliness of regulatory approvals; the continued demand for Arbutus’ assets; and the stability of economic and market conditions. While Arbutus considers these assumptions to be reasonable, these assumptions are inherently subject to significant business, economic, competitive, market and social uncertainties and contingencies, including uncertainties and contingencies related to the ongoing COVID-19 pandemic. Additionally, there are known and unknown risk factors which could cause Arbutus’ actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements contained herein. Known risk factors include, among others: anticipated pre-clinical studies and clinical trials may be more costly or take longer to complete than anticipated, and may never be initiated or completed, or may not generate results that warrant future development of the tested drug candidate; changes in Arbutus’ strategy regarding its product candidates and clinical development activities; Arbutus may not receive the necessary regulatory approvals for the clinical development of Arbutus’ products; economic and market conditions may worsen; market shifts may require a change in strategic focus; and the ongoing COVID-19 pandemic could significantly disrupt our clinical development programs. A more complete discussion of the risks and uncertainties facing Arbutus appears in Arbutus’ Annual Report on Form 10-K, Arbutus’ Quarterly Reports on Form 10-Q and Arbutus’ continuous and periodic disclosure filings, which are available at www.sedar.com and at www.sec.gov. All forward-looking statements herein are qualified in their entirety by this cautionary statement, and Arbutus disclaims any obligation to revise or update any such forward-looking statements or to publicly announce the result of any revisions to any of the forward-looking statements contained herein to reflect future results, events or developments, except as required by law. COVID-19. In December 2019 an outbreak of a novel strain of coronavirus (COVID-19) was identified in Wuhan, China. This virus continues to spread globally, has been declared a pandemic by the World Health Organization and has spread to nearly every country in the world. The impact of this pandemic has been, and will likely continue to be, extensive in many aspects of society. The pandemic has resulted in and will likely continue to result in significant disruptions to businesses. A number of countries and other jurisdictions around the world have implemented extreme measures to try and slow the spread of the virus. These measures include the closing of businesses and requiring people to stay in their homes, the latter of which raises uncertainty regarding the ability to travel to hospitals in order to participate in clinical trials. Additional measures that have had, and will likely continue to have, a major impact on clinical development, at least in the near- term, include shortages and delays in the supply chain, and prohibitions in certain countries on enrolling subjects in new clinical trials (e.g. in Australia). It is not possible to predict if the COVID-19 pandemic will negatively impact our plans and timelines. NASDAQ: ABUS www.arbutusbio.com
AB-729-001 Study Design PART 1: Single Ascending Dose PART 2: Single Doses PART 3: Multiple Doses In Healthy Subjects In Chronic Hepatitis B Subjects In Chronic Hepatitis B Subjects Cohort A: 180mg Dose 1 (60mg) Cohort E: 60mg HBV DNA - n=6; 4 active : 2 placebo n=6 HBV DNA - n=7 (≥ Day 15 Safety) (≥ Day 15 Safety) Cohort B: 60mg Dose 2 (180mg) Cohort F: TBD HBV DNA - n=6; 4 active : 2 placebo n=6 HBV DNA - n=7 (≥ Day 15 Safety) (≥ Day 15 Safety) Cohort C: 90mg Dose 3 (360mg) Cohort G: TBD + TDF HBV DNA - n=6; 4 active : 2 placebo n=6 HBV DNA + n=7 Cohort D: TBD HBV: Hepatitis B Virus NASDAQ: ABUS HBV DNA + n=6 www.arbutusbio.com TDF: tenofovir disoproxil fumarate TBD: to be determined
AB-729-001 Key Inclusion/Exclusion Criteria 1. Documented chronic hepatitis B infection; confirmed HBeAg positive or negative 2. HBV-DNA at screening: a) For HBV-DNA negative subjects (on a NA for at least 6 months): HBV-DNA <LLOQ b) For HBV-DNA positive subjects: HBV-DNA ≥1,000 IU/mL 3. HBsAg ≥250 IU/mL at screening 4. Non-cirrhotic with mild/moderate fibrosis defined by: a) Liver biopsy Metavir Fibrosis Score of F0-2 (or equivalent) within 12 months OR Fibroscan® result of ≤10 kPa within 6 months 5. ALT/AST <5x ULN for Part 2 and <2x ULN for Part 3; Tbili <1.5x ULN for all Parts NASDAQ: ABUS www.arbutusbio.com
AB-729-001 Chronic Hepatitis B Subject Demographics Cohort A: 180mg (n=4) Cohort B: 60mg (n=6) Age (mean, range) 42.8 (35-53) 48.2 (33-56) Male Gender (n, percentage) 3 (75%) 3 (50%) Asian Race (n, percentage) 0 (0%) 3 (50%) Hepatitis B e-Antigen Negative (n, percentage) 3 (75%) 6 (100%) Baseline Hepatitis B Surface Antigen (mean, 8,577 (4,720 - 10,289) IU/mL 2,095 (405 – 5,110) IU/mL range) NASDAQ: ABUS www.arbutusbio.com
AB-729-001: Healthy Volunteer Safety •No SAEs across all doses •15 AEs in total; 4 study drug-related AEs •Dose 1 (60 mg): • No clinically significant changes in vital signs, lab parameters or ECG abnormalities •Dose 2 (180 mg): • 1 Grade 1 drug-related AE (erythema at injection site) • 1 Lab abnormality (not drug-related): 1 Grade 2 ALT elevation (resolved) • No clinically significant changes in vital signs, other lab parameters or ECG abnormalities •Dose 3 (360 mg): • 3 Lab abnormalities: 2 subjects with Grade 3 and 1 subject with Grade 1 asymptomatic ALT elevations (resolved). These 3 subjects had Grade 2 and Grade 1 AST elevations. • No clinically significant changes in vital signs, other lab parameters or ECG abnormalities NASDAQ: ABUS www.arbutusbio.com
AB-729-001: Chronic Hepatitis B Subject Safety •No SAEs across both doses. 12 AEs in total; 8 study drug-related AEs 180mg Cohort 60mg Cohort 6 related AEs in 3 subjects: 2 related AEs in 2 subjects: • 4 Grade 1 AEs – increased ALT and AST in 2 subjects • 2 Grade 1 AEs – injection site redness and injection • 2 Grade 2 AEs – headache in 2 subjects site pruritis No clinically relevant changes in vital signs, No clinically relevant changes in vital signs, other lab parameters or ECGs other lab parameters or ECGs 3 unrelated AEs in 1 subject#: • 1 Grade 2 AE – gastroenteritis* • 2 Grade 3 AEs – Increased ALT and AST* *Self-medication with unapproved concomitant medications including 2% papaverine intramuscular injection (known to be associated with NASDAQ: ABUS transaminase elevations) www.arbutusbio.com #Self-discontinuation of tenofovir reported starting mid-December (~12 weeks post-dose), earlier compliance unclear
Individual HBsAg Change From Baseline in Chronic Hepatitis B Subjects 29 Days After a Single Dose of AB-729 60 mg Cohort 180 mg Cohort Mean Day 29: -0.44 log10 IU/mL Mean Day 29: (n=3) -0.24 log10 IU/mL (n=6) Mean Day 29: Mean Day 29: -0.81 log10 IU/mL -0.51 log10 IU/mL (n=3) (n=4) -1.94 log10 IU/mL NASDAQ: ABUS www.arbutusbio.com ATAFD: actual time after first dose
Individual HBsAg Change From Baseline in Chronic Hepatitis B Subjects After a Single Dose of AB-729: Long Term Follow Up 180 mg HBsAg Nadir -1.94 log10 IU/mL -1.17 log IU/mL Mean Wk 12: 10 -0.73 log10 IU/mL -0.98 log10 IU/mL (n=4) -1.10 log10 IU/mL Mean Wk 12: •Reduction in HBsAg observed in two -0.77 log10 IU/mL (n=3) subjects through day 120 •Response appears to plateau through day 180 NASDAQ: ABUS www.arbutusbio.com ATAFD: actual time after first dose
Q&A