UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
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FORM
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CURRENT REPORT
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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).
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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. ☐
On November 15, 2020, the Company issued a press release announcing the November 15, 2020 presentation of the Phase 1a/1b clinical trial results for AB-729 in chronic hepatitis B subjects, at The Liver Meeting Digital Experience(TM), The American Association for the Study of Liver Diseases Meeting. A copy of the press release is filed herewith as Exhibit 99.1 and is incorporated by reference herein.
On November 16, 2020, Arbutus Biopharma Corporation (the "Company") issued a press release announcing positive additional data from the ongoing AB-729 Phase 1a/1b clinical trial results in chronic hepatitis B subjects, for the 60 mg multi-dose cohort, and the first results for the 90 mg single-dose cohort of HBV DNA positive subjects. A copy of the press release is filed herewith as Exhibit 99.2 and is incorporated by reference herein.
Also on November 16, 2020, the Company held a conference call and webcast presentation to discuss the positive results for the additional data for AB-729. A copy of the presentation is filed herewith as Exhibit 99.3 and is incorporated by reference herein.
(d) Exhibits.
| Exhibit Number | Description | |
| 99.1 | Press release dated November 15, 2020 | |
| 99.2 | Press release dated November 16, 2020 | |
| 99.3 | Presentation dated November 16, 2020 | |
| 104 | Cover page interactive data file (formatted as inline XBRL). |
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: November 16, 2020 | By: | /s/ David C. Hastings |
| David C. Hastings | ||
| Chief Financial Officer | ||
EXHIBIT 99.1
Arbutus Announces Presentation of Phase 1a/1b Clinical Trial Results for AB-729 in Chronic Hepatitis B Subjects at The Liver Meeting Digital Experience™, The American Association for the Study of Liver Diseases Meeting
Across all single-dose cohorts, mean HBsAg concentrations continuously declined up to week 12 before reaching a plateau, suggesting dosing of AB-729 less frequently than every 4 weeks may be warranted
In the 60 mg every 4 weeks multi-dose cohort, HBsAg concentrations continued to decline steadily beyond week 12 with no plateau in response observed to date
Both HBV RNA and HBcrAg concentrations declined after single- and multi-dose administration of AB-729
AB-729 was generally safe and well tolerated
Conference Call and Webcast Scheduled for Monday, November 16, 2020 at 8:00 am ET
WARMINSTER, Pa., Nov. 15, 2020 (GLOBE NEWSWIRE) -- Arbutus Biopharma Corporation (Nasdaq: ABUS), a clinical-stage biopharmaceutical company primarily focused on developing a cure for people with chronic hepatitis B virus (HBV) infection as well as therapies to treat coronaviruses (including COVID-19), today announced the presentation of updated clinical data from an ongoing Phase 1a/1b clinical trial (AB-729-001) with AB-729, its proprietary GalNAc delivered RNAi compound. The presentation, entitled Safety and pharmacodynamics of the GalNAc-siRNA AB-729 in subjects with chronic hepatitis B infection, was presented by Professor Man-Fung Yuen, D.Sc., M.D., Ph.D., Chief of Division of Gastroenterology and Hepatology, Department of Medicine, The University of Hong Kong, Hong Kong, during a virtual oral session: Hepatitis B: Therapeutics (New) at The Liver Meeting Digital ExperienceTM, The American Association for the Study of Liver Diseases Meeting.
Summary of presented data
Single-doses of AB-729 studied to date, 60 mg, 90 mg and 180 mg, resulted in comparable mean HBsAg declines at week 12, followed by a sustained plateau phase. During the multiple-dose portion of the trial, 60 mg of AB-729 dosed every 4 weeks resulted in continuous declines in HBsAg, reaching a mean of –1.44 log10 IU/ML at week 16. Data beyond week 16 demonstrate further declines in HBsAg with no plateau seen to date. AB-729 also resulted in meaningful decreases in both HBV RNA and HBcrAg. AB-729 was generally safe and well tolerated. The presentation can be accessed through the Investors section under Events & Presentations of Arbutus' website at www.arbutusbio.com.
Repeat dosing of AB-729 60 mg every 4 weeks results in continuous HBsAg declines beyond week 12
| Mean (SE) Week 12 N=7 | Mean (SE) Week 16 N=7 | Mean (SE) Week 20 N=3 | |
| Δlog10 HBsAg (IU/mL) | -1.10 (0.15) | -1.44 (0.18) | -1.73 (0.12) |
Professor Yuen stated “These are the first multi-dose data for AB-729 and show continuous decline of HBsAg throughout the dosing period. Importantly, AB-729 was generally safe and well tolerated. These encouraging data support the continued development of AB-729 as a potential cornerstone of future combination regimens for the treatment of chronic hepatitis B infection.”
Summary of clinical trial design
AB-729-001 is an ongoing first-in-human clinical trial consisting of three parts:
In Part 1, three cohorts of healthy subjects were randomized 4:2 to receive single-doses (60 mg, 180 mg or 360 mg) of AB-729 or placebo.
In Part 2, non-cirrhotic, HBeAg positive or negative, chronic HBV subjects (N=6) on a background of nucleos(t)ide therapy with HBV DNA below the limit of quantitation received single-doses (60 mg to 180 mg) of AB-729. An additional cohort in Part 2 included 90 mg single-dose of AB-729 in HBV DNA positive chronic HBV subjects.
In Part 3, chronic HBV subjects, HBV DNA negative first and HBV DNA positive later, are receiving multi-doses of AB-729 for up to six months.
About AB-729
AB-729 is an 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. In an ongoing single- and multi-dose Phase 1a/1b clinical trial, AB-729 demonstrated positive safety and tolerability data and meaningful reductions in hepatitis B surface antigen.
About HBV
Chronic hepatitis B virus (HBV) infection is a debilitating disease of the liver that afflicts over 250 million people worldwide with up to 90 million people in China, as estimated by the World Health Organization. HBV is a global epidemic that affects more people than hepatitis C virus (HCV) and HIV infection combined—with a higher morbidity and mortality rate. HBV is a leading cause of chronic liver disease and need for liver transplantation, and up to one million people worldwide die every year from HBV-related causes.
The current standard of care for patients with chronic HBV infection is life-long suppressive treatment with medications that reduce, but do not eliminate, the virus, resulting in very low cure rates. There is a significant unmet need for new therapies to treat HBV.
Conference Call and Webcast
Arbutus will hold a conference call and webcast on Monday, November 16, 2020 at 8:00 am Eastern Time to provide an AB-729 clinical update. You can access a live webcast of the call, which will include presentation slides, through the Investors section of Arbutus’ website at www.arbutusbio.com or directly at Live Webcast. Alternatively, you can dial (866) 393-1607 or (914) 495-8556 and reference conference ID 7791835.
An archived webcast will be available on the Arbutus website after the event. Alternatively, you may access a replay of the conference call by calling (855) 859-2056 or (404) 537-3406, and reference conference ID 7791835.
About Arbutus
Arbutus Biopharma Corporation is a publicly traded (Nasdaq: ABUS) biopharmaceutical company primarily dedicated to discovering, developing and commercializing a cure for people with chronic hepatitis B virus (HBV) infection. The Company is advancing multiple drug product candidates that may be combined into a potentially curative regimen for chronic HBV infection. Arbutus has also initiated a drug discovery and development effort for treating coronaviruses (including COVID-19). For more information, please 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 regarding the Company’s expectation that AB-729 could be the cornerstone of future combination regimens for the treatment of chronic hepatitis B infection.
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 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; Arbutus may elect to change its 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 Arbutus’ 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: 267-469-0914
Email: ir@arbutusbio.com
Pam Murphy
Investor Relations Consultant
Phone: 267-469-0914
Email: ir@arbutusbio.com
EXHIBIT 99.2
Arbutus Announces Additional Robust HBsAg Decline Data with AB-729 in Chronic Hepatitis B Subjects
Data released today expands on November 15, 2020 AASLD presentation
Repeat dosing of 60 mg AB-729 every 4 weeks resulted in robust and continuous mean declines in HBsAg decline at week 20 (-1.71 log10IU/mL, N=7) and further reductions continued beyond week 20 (-1.84 log10 IU/mL, N=3)
In HBV DNA positive subjects, a single 90 mg AB-729 dose resulted in robust mean declines in HBsAg (-1.02 log10 IU/mL), HBV DNA (-1.53 log10 IU/mL), HBV RNA and HBcrAg at week 12
Results support advancement into Phase 2 combination clinical trials with AB-729 dosing as infrequently as every 8 or 12 weeks
Conference Call and Webcast Scheduled Today at 8:00 am ET
WARMINSTER, Pa., Nov. 16, 2020 (GLOBE NEWSWIRE) -- Arbutus Biopharma Corporation (Nasdaq: ABUS), a clinical-stage biopharmaceutical company primarily focused on developing a cure for people with chronic hepatitis B virus (HBV) infection as well as therapies to treat coronaviruses (including COVID-19), today announced additional clinical data from an ongoing Phase 1a/1b clinical trial (AB-729-001) with AB-729, its proprietary GalNAc delivered RNAi compound.
The new data described today expands on the presentation entitled Safety and pharmacodynamics of the GalNAc-siRNA AB-729 in subjects with chronic hepatitis B infection, recorded on October 14, 2020 and presented on November 15, 2020 by Professor Man-Fung Yuen, D.Sc., M.D., Ph.D., from the University of Hong Kong at The Liver Meeting Digital ExperienceTM, The American Association for the Study of Liver Diseases (AASLD) Meeting.
The new data summarized below include HBsAg data for the complete 60 mg every 4 weeks multi-dose cohort (N=7) at week 20, and the first results for the AB-729 90 mg single-dose cohort of HBV DNA positive subjects (N=5).
William Collier, President and Chief Executive Officer of Arbutus, stated, “The positive data described today, together with the strong safety and efficacy results presented by Professor Yuen at AASLD yesterday, are encouraging and continue to support our confidence in the therapeutic value of AB-729 as we plan to move into Phase 2 clinical trials.”
Summary of new data
Repeat dosing of AB-729 60 mg every 4 weeks results in continuous declines in mean HBsAg through week 20 (Cohort E)
| Mean (SE) Week 16 N=7 | Mean (SE) Week 20 N=7 | Mean (SE) Week 24 N=3 | |
| Δlog10 HBsAg (IU/mL) | -1.44 (0.18) | -1.71 (0.18) | -1.84 (0.10) |
Dr. Gaston Picchio, Chief Development Officer at Arbutus stated, “Further follow up of the 60 mg every 4 weeks multi-dose cohort confirmed continuous reductions in mean HBsAg at week 20 (N=7), and in a subset of subjects (N=3) beyond this time point, while being generally safe and well tolerated. Additionally, the mean HBsAg declines and slopes of declines are similar between single doses and repeat doses of AB-729 up to week 12. Importantly, this suggests that dosing AB-729 as frequently as every 4 weeks may not be necessary, and that AB-729 has the potential to be dosed every 8 weeks or even every 12 weeks. This dosing strategy is being investigated in other cohorts of the trial with results from the 60 mg every 8 week cohort expected before the end of 2020.”
AB-729 90 mg single-dose reduces HBsAg and HBV DNA in HBV DNA positive chronic Hepatitis B (CHB) subjects with mean HBsAg declines similar to those seen in HBV DNA negative subjects (Cohort D)
| Mean (SE) Week 12 N=5 | ||
| Δlog10 HBsAg (IU/mL) | -1.02 (0.13) | |
| Δlog10 HBV DNA (IU/mL) | -1.53 (0.24) |
Dr. Picchio added, “It is also encouraging to observe that a single 90 mg dose of AB-729 is capable of reducing HBsAg in HBV DNA positive subjects to the same extent achieved in other single-dose HBV DNA negative cohorts. Further, a single 90 mg AB-729 dose substantially reduced HBV DNA as well as HBV RNA and HBcrAg.”
AB-729 was safe and well tolerated after single and repeat doses
- No serious adverse events or discontinuations due to adverse events
- No treatment-related Grade 3 or 4 adverse events
Summary of clinical trial design
AB-729-001 is an ongoing first-in-human clinical trial consisting of three parts:
In Part 1, three cohorts of healthy subjects were randomized 4:2 to receive single-doses (60 mg, 180 mg or 360 mg) of AB-729 or placebo.
In Part 2, non-cirrhotic, HBeAg positive or negative, chronic HBV subjects (N=6) on a background of nucleos(t)ide therapy with HBV DNA below the limit of quantitation received single-doses (60 mg to 180 mg) of AB-729. An additional cohort in Part 2 included 90 mg single-dose of AB-729 in HBV DNA positive chronic HBV subjects.
In Part 3, chronic HBV subjects, HBV DNA negative first and HBV DNA positive later, are receiving multi-doses of AB-729 for up to six months.
About AB-729
AB-729 is an 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. In an ongoing single- and multi-dose Phase 1a/1b clinical trial, AB-729 demonstrated positive safety and tolerability data and meaningful reductions in hepatitis B surface antigen.
About HBV
Chronic hepatitis B virus (HBV) infection is a debilitating disease of the liver that afflicts over 250 million people worldwide with up to 90 million people in China, as estimated by the World Health Organization. HBV is a global epidemic that affects more people than hepatitis C virus (HCV) and HIV infection combined—with a higher morbidity and mortality rate. HBV is a leading cause of chronic liver disease and need for liver transplantation, and up to one million people worldwide die every year from HBV-related causes.
The current standard of care for patients with chronic HBV infection is life-long suppressive treatment with medications that reduce, but do not eliminate, the virus, resulting in very low cure rates. There is a significant unmet need for new therapies to treat HBV.
Conference Call and Webcast Today
Arbutus will hold a conference call and webcast today, Monday, November 16, 2020 at 8:00 am Eastern Time to provide an AB-729 clinical update. You can access a live webcast of the call, which will include presentation slides, through the Investors section of Arbutus’ website at www.arbutusbio.com or directly at Live Webcast. Alternatively, you can dial (866) 393-1607 or (914) 495-8556 and reference conference ID 7791835.
An archived webcast will be available on the Arbutus website after the event. Alternatively, you may access a replay of the conference call by calling (855) 859-2056 or (404) 537-3406, and reference conference ID 7791835.
About Arbutus
Arbutus Biopharma Corporation is a publicly traded (Nasdaq: ABUS) biopharmaceutical company primarily dedicated to discovering, developing and commercializing a cure for people with chronic hepatitis B virus (HBV) infection. The Company is advancing multiple drug product candidates that may be combined into a potentially curative regimen for chronic HBV infection. Arbutus has also initiated a drug discovery and development effort for treating coronaviruses (including COVID-19). For more information, please 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 the Company’s expectations to conduct Phase 2 combination studies with AB-729 dosing as infrequently as every 8 or 12 weeks; the Company’s expectation that AB-729 could be effective at dosing intervals of every 8 or even every 12 weeks; the Company’s expectations that additional data results from the AB-729 60 mg 8 week cohort will be available before the end of 2020; and the Company’s expectation that AB-729 could be the cornerstone of future combination regimens for the treatment of chronic hepatitis B infection.
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 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; Arbutus may elect to change its 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 Arbutus’ 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: 267-469-0914
Email: ir@arbutusbio.com
Pam Murphy
Investor Relations Consultant
Phone: 267-469-0914
Email: ir@arbutusbio.com
EXHIBIT 99.3
NASDAQ: ABUS www.arbutusbio.com AB - 729 Clinical Update Dr. Gaston Picchio Chief Development Officer November 16, 2020
Forward - Looking Statements This presentation contains forward - looking statements within the meaning of the U . S . Private Securities Litigation Reform Act of 1995 and Canadian securities laws . All statements that are not historical facts are hereby identified as forward - looking statements for this purpose and include, among others, statements relating to Arbutus’ expectations to conduct Phase 2 combination studies with AB - 729 dosing as infrequently as every 8 or 12 weeks ; Arbutus’ expectation that AB - 729 could be effective at dosing intervals of every 8 or even every 12 weeks ; Arbutus’ expectations that additional data results from the AB - 729 60 mg 8 week cohort will be available before the end of 2020 ; Arbutus’ expectation that AB - 729 could be the cornerstone of future combination regimens for the treatment of chronic hepatitis B infection ; and other statements relating to Arbutus’ future operations, future financial performance, future financial condition, prospects or other future events . With respect to the forward - looking statements contained in this presentation, Arbutus has made numerous assumptions regarding, among other things : the timely receipt of expected payments ; 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 . Forward - looking statements herein involve known and unknown risks, uncertainties and other factors that may cause the actual results, events or developments to be materially different from any future results, events or developments expressed or implied by such forward - looking statements . Such factors include, among others : anticipated pre - clinical 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 ; and 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, Quarterly Report on Form 10 - Q and Arbutus' periodic disclosure filings which are available at www . sec . gov and at www . sedar . com . 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 .
AB - 729 - 001 Study Overview Presentation includes data available through 06 - Nov - 2020 HBV: Hepatitis B Virus | TDF: tenofovir disoproxil fumarate (≥ Day 15 Safety) Cohort A: 180 mg HBV DNA - n =4 Cohort B: 60 mg HBV DNA - n =6 Cohort C: 90 mg HBV DNA - n =6 Cohort D: 90 mg HBV DNA + n =6 Part 2: Single Doses in Chronic Hepatitis B Subjects (open - label) Part 1: Single Ascending Dose in Healthy Subjects Dose 1 (60 mg) n=6; 4 active : 2 placebo (≥ Day 15 Safety) Dose 2 (180 mg) n=6; 4 active : 2 placebo Dose 3 (360 mg) n=6; 4 active : 2 placebo (≥ Day 15 Safety) Cohort E: 60 mg Q4W HBV DNA - n =7 Part 3: Repeat Doses in Chronic Hepatitis B Subjects (open - label) Cohort I: 90 mg Q 8 W H B V DN A - n =7 Cohort J: 90 mg Q12W HBV DNA - n =7 Cohort F: 60 mg Q8W HBV DNA - n =7 Cohort G: 90 mg Q8W + TDF: HBV DNA + n = 7 upd a t e (≥ Day 15 Safety) n e w
Baseline Characteristics Baseline Measure Cohort A 180 mg (N=4) Cohort B 60 mg (N=6) Cohort C 90 mg (N=6) Cohort D HBV DNA+ 90 mg (N=5*) Cohort E 60 mg Q4W (N=7) Age in years, mean (range) 42.8 (35 - 53) 48.2 (33 - 56) 54.8 (47 - 62) 43.6 (35 - 57) 45.1 (33 - 63) Male gender, n (%) 3 (75%) 3 (50%) 6 (100%) 3 (60%) 4 (57%) BMI, mean (SD) 23.7 (3.62) 26.6 (3.23) 25.2 (1.96) 29.2 (5.42) 27.7 (5.01) Race, n (%) Asian 0 3 (50%) 6 (100%) 0 1 (14%) White 4 (100%) 3 (50%) 0 4 (80%) 6 (86%) Pacific Islander 0 0 0 1 (20%) 0 ALT (U/L), mean (SD) 39.3 (35.36) 20.0 (6.52) 25.5 (9.23) 31.6 (13.43) 22.4 (10.52) HBV eAg negative, n (%) 3 (75%) 6 (100%) 6 (100%) 5 (100) 7 (100%) HBsAg (IU/mL), mean (range) 8577 (4720 – 10289) 2095 (405 – 5110) 822 (261 – 1400) 2336 (317 – 6451) 5372 (584 – 11761) HBV DNA (IU/mL), mean (range) N/A N/A N/A 86840 (1220 – 360560) N/A *One subject experienced a spontaneous HBV flare prior to dosing and was excluded from the analysis
Mean (SE) Week 12: - 1.10 (0.15) Mean (SE) Week 16: - 1.44 (0.18) Mean (SE) Week 20 : - 1.71 (0.18) Mean (SE) Week 24 : - 1.84 (0.10) [N=3] Repeat dosing of AB - 729 60 mg every 4 weeks results in continuous mean HBsAg declines beyond Week 12 5/7 HBsAg <100 IU/mL 1/7 HBsAg <10 IU/mL AB - 729 60 mg Q4W Mean ( ц SE) HBsAg declines across Cohorts Mean Individual *N=5 at Week 10, 14, 18 and 22 **N=4 at Week 14 - 20; N=3 at Weeks 22 – 24 # N=6 at Week 6; N=3 at Week 24 SD: single dose; Q4W: every 4 weeks
AB - 729 90 mg single dose reduces HBsAg and HBV DNA in HBV DNA positive CHB subjects 2/5 HBsAg <100 IU/mL 0/5 HBsAg <10 IU/mL HBsAg (N=5) HBV DNA (N=5) Mean HBsAg decline is similar to HBV DNA negative CHB subjects Mean Individual Week 12 - 2 .5 - 2 - 1 .5 - 1 - 0 .5 0 0 .5 0 8 10 12 Week 12 - 2 .5 - 2 - 1 .5 - 1 - 0 .5 0 0 .5 0 2 4 6 8 10 12 Week 12 mean (SE): - 1.02 (0.13) Week 12 mean (SE): - 1.53 (0.24) M e an Individual ∆log 10 HBsAg (IU/mL) ∆log 10 HBV DNA (IU/mL) 2/5 HBsAg <100 IU/mL 0/5 HBsAg <10 IU/mL 2 4 6 W eek W eek
Different response profiles following a single dose of AB - 729 90 mg in HBV DNA positive CHB subjects Subject A profile Subject B profile H B s Ag HBV DNA - 2 .5 - 2 - 1 .5 - 1 - 0 .5 0 0.5 0 2 4 6 8 10 12 - 2 .5 - 2 - 1 .5 - 1 - 0 .5 0 0 .5 0 2 4 8 10 12 6 W eek ∆log 10 HBsAg and HBV DNA (IU/mL) ∆log 10 HBsAg and HBV DNA (IU/mL) W eek
AB - 729 reduces HBV RNA and HBcrAg to the limits of quantification or detection in most HBV DNA+ subjects 4/5 subjects reached <LLOQ (*) or TND (#) 2/3 subjects reached <LLOQ (*) * * * # # # Maximum reductions shown up to Week 12 in subjects with quantifiable data at baseline HBV RNA HBcrAg LLOQ = lower limit of quantitation; TND = target not detected; SD = single dose HBcrAg samples <LLOQ (3.0 log10 IU/mL) assigned a value of 2.9 log10 IU/mL HBV RNA samples <LLOQ (1.65 log10 IU/mL) or target not detected assigned a value of 1.64 log10 IU/mL
AB - 729 was safe and well tolerated after single and repeat doses Subjects, n (%) Cohort A ( 180 mg) N= 4 Subjects with any TEAE 4 (100) Subjects with related TEAEs Grade 1 Grade 2 Grade 3 Grade 4 3 (75) 1 (25) 2 (50) 0 0 Most common related TEAEs (in ≥ 2 subjects): ALT elevation# AST elevation Headache 2 (50) 1 (25) 2 (50) Injection site pain Injection site erythema Injection site bruising 0 0 0 ▪ No SAEs or discontinuations due to AEs ▪ No treatment - related Grade 3 or 4 AEs - 1 subject (Cohort A) with rapid decline in HBsAg of ~2.0 log10 IU/mL had an unrelated Gr 2 AE of food poisoning resulting in unrelated transient Grade 3 AEs of ALT/AST elevation (without bilirubin changes) ▪ No other Grade 2, 3 or 4 laboratory abnormalities ▪ Injection site TEAEs were mild (erythema, pain, pruritis, bruising) or moderate (pain) and transient ▪ No clinically meaningful changes in ECGs or vital signs *One subject experienced a spontaneous HBV flare prior to dosing and was excluded from the analysis Grading criteria based on Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1., July, 2017 #ALT and AST elevations were all Grade 1 excepting two Grade 2 ALT in Cohort E, all were asymptomatic without bilirubin changes † 4/5 subjects from same site; 2 Gr 2 TEAEs had AB - 729 dose erroneously split into 2 injections, all TEAEs lasted <1 hour ‡ n, % is number of events out of 63 total AB - 729 doses administered
Additional data presented today further reinforces efficacy and safety of AB - 729 In Cohort E, repeat 60 mg Q4W dosing with AB - 729 resulted in a continuous and robust HBsAg decline at week 20 ( - 1.71 log10 IU/mL). Further reductions continued beyond week 20 ( - 1.84 log10 IU/mL, N=3) ▪ No plateau effect in HBsAg decline observed to date during repeat dosing In HBV DNA positive CHB subjects, a single 90 mg AB - 729 dose resulted in robust mean HBsAg ( - 1.02 log10 IU/mL) and HBV DNA ( - 1.53 log10 IU/mL) declines at week 12, as well as decreases in HBV RNA and core - related antigen ▪ Similar HBsAg reductions were observed in HBV DNA positive and negative CHB subjects ▪ These findings support complete target engagement by AB - 729 AB - 729 remains generally safe and well tolerated These results support advancing AB - 729 to Phase 2 combination studies with AB - 729 dosing as infrequently as every 8 or 12 weeks