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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On November 7, 2023, Arbutus Biopharma Corporation (the “Company”) issued a press release announcing its financial results for the third quarter ended September 30, 2023 and certain other information. A copy of the press release is furnished as Exhibit 99.1 hereto and is incorporated by reference herein.
On November 7, 2023, the Company posted an updated corporate presentation on its website at www.arbutusbio.com. A copy of the presentation is filed herewith as Exhibit 99.2 and is incorporated by reference herein.
On November 6, 2023, the Company reduced its workforce by 24% primarily affecting its research function. As a result, the Company will incur a one-time restructuring charge of approximately $1.1 million that will be recorded in the fourth quarter of 2023. The Company remains committed to continuing discovery research in chronic HBV.
(d) Exhibits.
| Exhibit Number | Description | |||
| 99.1 | Press release dated November 7, 2023 | |||
| 99.2 | Corporate Presentation dated November 7, 2023 | |||
| 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 7, 2023 | By: | /s/ David C. Hastings |
| David C. Hastings | ||
| Chief Financial Officer | ||
EXHIBIT 99.1
Arbutus Reports Third Quarter 2023 Financial Results and Provides Corporate Update
Multiple data presentations upcoming at AASLD – The Liver Meeting®, including preliminary data from Phase 2a clinical trial combining imdusiran, our RNAi therapeutic, with VTP-300, an HBV antigen-specific immunotherapy
Dosing continues in two Phase 2a combination clinical trials with imdusiran and in a Phase 1a/1b clinical trial with AB-101, our oral PD-L1 checkpoint inhibitor
Reducing workforce by 24% as a result of recent pipeline optimization
Cash runway extended into first quarter 2026
Conference Call and Webcast Today at 8:45 AM ET
WARMINSTER, Pa., Nov. 07, 2023 (GLOBE NEWSWIRE) -- Arbutus Biopharma Corporation (Nasdaq: ABUS) (“Arbutus” or the “Company”), a clinical-stage biopharmaceutical company leveraging its extensive virology expertise to develop a cure for people with chronic hepatitis B virus (cHBV) infection, today reported third quarter 2023 financial results and provided a corporate update.
“We are looking forward to our upcoming data presentations at the American Association for the Study of Liver Diseases (AASLD) – The Liver Meeting® 2023, specifically the preliminary data from the Phase 2a clinical trial, AB-729-202, evaluating imdusiran, our RNAi therapeutic, in combination with VTP-300 and a nucleos(t)ide analogue in patients with chronic hepatitis B virus,” said William Collier, President and Chief Executive Officer of Arbutus Biopharma. “These data have the potential to support our hypothesis that a functional cure for cHBV can be achieved by reducing surface antigen, suppressing HBV DNA and boosting the immune system. We continue to explore imdusiran as a cornerstone therapy as we dose patients in the additional treatment arm of the AB-729-202 trial that adds a low dose of nivolumab (Opdivo®), an anti-PD-1 monoclonal antibody, to the triple combination, as well as continuing to dose and follow patients in the on-going AB-729-201 clinical trial combining imdusiran with short durations of Peg-IFNα-2a and ongoing NA therapy. In addition, we have dosed our first group of healthy subjects in our Phase 1a/1b clinical trial with AB-101 and are on-track to report data from the first part of this trial in the first half of 2024. We look forward to sharing additional updates on our progress in the coming months.”
Mr. Collier, continued, “Following our recent pipeline optimization, we made the difficult decision to reduce our workforce as we continue to manage our operating expenses. I’d like to thank our departing employees for their dedication and valuable contributions towards our mission. The Company remains committed to continuing discovery research in chronic HBV.”
Pipeline Updates and Key Milestones
Imdusiran (AB-729, RNAi Therapeutic)
- Arbutus will be presenting preliminary data at AASLD from the first group of patients in its Phase 2a clinical trial (AB-729-202) that is evaluating imdusiran, nucleos(t)ide analogue (NA) therapy and Barinthus Bio’s (formerly Vaccitech plc) VTP-300, an HBV antigen-specific immunotherapy.
Enrollment is ongoing in the expanded cohort of the AB-729-202 clinical trial that is designed to enroll 20 patients who will receive imdusiran (60mg every 8 weeks) plus NA therapy for 24 weeks followed by VTP-300 plus up to two doses of low-dose nivolumab. Preliminary data from this additional treatment arm are expected in 2024.
- Follow-up is continuing in the Company’s on-going Phase 2a clinical trial (AB-729-201), evaluating the safety, tolerability and antiviral activity of the combination of imdusiran and pegylated interferon alfa-2a (IFN) in patients with cHBV. Preliminary data presented at the EASL Congress in June 2023 suggest that the addition of IFN to imdusiran was generally well tolerated and appears to result in continued HBsAg declines in some patients. Arbutus plans to provide updates from this clinical trial in 2024.
AB-101 (Oral PD-L1 Inhibitor)
- In September, the Company dosed the first subject in its Phase 1a/1b double-blind, randomized, placebo-controlled, clinical trial (AB-101-001) designed to investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple oral doses of AB-101 for up to 28 days in healthy subjects and patients with cHBV. The trial will be conducted in three parts starting with single ascending doses in healthy subjects, followed by multiple ascending doses in healthy subjects and culminating with multiple doses in patients with cHBV. Safety and PK/PD assessments will be performed prior to dose escalation in all trial parts. Initial data from part one of the trial are expected in the first half of 2024.
Corporate Updates
In connection with the Company’s decision in September to focus its pipeline on its HBV clinical stage compounds and discontinue its research programs, Arbutus has taken steps to streamline its organization and has reduced its workforce by 24%, effective November 6, 2023, primarily affecting its research function. As a result, Arbutus will incur a one-time restructuring charge of approximately $1.1 million that will be recorded in the fourth quarter of 2023.
With the organizational changes announced today and its ongoing cost management efforts, the Company now expects its current cash, cash equivalents and investments will be sufficient to fund its operations into the first quarter of 2026. The Company remains committed to continuing discovery research in chronic HBV.
In a separate press release issued today, Arbutus announced that William Collier will be retiring as President and CEO, as well as a member of the Company’s Board of Directors, at the end of 2023 and Michael J. McElhaugh, Arbutus Co-founder and COO, will serve as interim CEO and will join the Company's Board of Directors.
The above corporate updates do not affect the Company’s pending litigations. Arbutus will continue to protect and defend its intellectual property, which is the subject of the on-going lawsuits against Moderna and Pfizer/BioNTech. The Company is seeking fair compensation for Moderna’s and Pfizer/BioNTech’s use of its patented LNP technology that was developed with great effort and at a great expense, without which Moderna and Pfizer/BioNTech’s COVID-19 vaccines would not have been successful. Document production is currently on-going in the lawsuit against Moderna with the claim construction hearing scheduled for February 7, 2024. Document and written discovery in the lawsuit against Pfizer/BioNTech is ongoing and a date for a claim construction hearing has not been set.
Financial Results
Cash, Cash Equivalents and Investments
As of September 30, 2023, we had cash, cash equivalents and investments in marketable securities of $144.7 million compared to $184.3 million as of December 31, 2022. During the nine months ended September 30, 2023, we used $68.6 million in operating activities, which was partially offset by $26.0 million of net proceeds from the issuance of common shares under our “at-the-market” offering program. We expect our 2023 net cash burn to range from between $90 to $95 million, excluding any proceeds received from our “at the market program”. We believe our cash runway will be sufficient to fund our operations into the first quarter of 2026.
Revenue
Total revenue was $4.7 million for the three months ended September 30, 2023, compared to $6.0 million for the same period in 2022. The decrease of $1.3 million was due primarily to a decrease in royalty revenue because of a decrease in Alnylam’s sales of ONPATTRO.
Operating Expenses
Research and development expenses were $20.2 million for the three months ended September 30, 2023 compared to $20.1 million for the same period in 2022. A decrease in expenses for drug supply manufacturing for our imdusiran Phase 2a clinical trials and expenses for our AB-836 Phase 1a/1b clinical trial, which was discontinued in the fourth quarter of 2022, were offset by an increase in expenses for our ongoing AB-101 clinical trial and our coronavirus program, which was discontinued in the third quarter of 2023. General and administrative expenses were $5.8 million for the three months ended September 30, 2023, compared to $3.5 million for the same period in 2022. This increase was due primarily to increases in employee-related costs, including non-cash stock-based compensation expense, and professional fees.
Net Loss
For the three months ended September 30, 2023, our net loss was $20.1 million, or a loss of $0.12 per basic and diluted common share, as compared to a net loss of $17.6 million, or a loss of $0.12 per basic and diluted common share, for the three months ended September 30, 2022.
Outstanding Shares
As of September 30, 2023, we had approximately 167.7 million common shares issued and outstanding, as well as approximately 21.0 million stock options and unvested restricted stock units outstanding. Roivant Sciences Ltd. owned approximately 23% of our outstanding common shares as of September 30, 2023.
UNAUDITED CONDENSED CONSOLIDATED STATEMENTS OF LOSS
(in thousands, except share and per share data)
| Three Months Ended September 30, | Nine Months Ended September 30, | ||||||||||||||
| 2023 | 2022 | 2023 | 2022 | ||||||||||||
| Revenue | |||||||||||||||
| Collaborations and licenses | $ | 3,935 | $ | 3,607 | $ | 13,329 | $ | 27,381 | |||||||
| Non-cash royalty revenue | 723 | 2,345 | 2,667 | 5,393 | |||||||||||
| Total revenue | 4,658 | 5,952 | 15,996 | 32,774 | |||||||||||
| Operating expenses | |||||||||||||||
| Research and development | 20,169 | 20,055 | 56,136 | 61,459 | |||||||||||
| General and administrative | 5,842 | 3,493 | 17,374 | 13,585 | |||||||||||
| Change in fair value of contingent consideration | 205 | 215 | (158 | ) | 624 | ||||||||||
| Total operating expenses | 26,216 | 23,763 | 73,352 | 75,668 | |||||||||||
| Loss from operations | (21,558 | ) | (17,811 | ) | (57,356 | ) | (42,894 | ) | |||||||
| Other income (loss) | |||||||||||||||
| Interest income | 1,494 | 694 | 4,223 | 1,249 | |||||||||||
| Interest expense | (46 | ) | (429 | ) | (415 | ) | (1,417 | ) | |||||||
| Foreign exchange gain | 6 | (21 | ) | 11 | (18 | ) | |||||||||
| Total other income (loss) | 1,454 | 244 | 3,819 | (186 | ) | ||||||||||
| Loss before income taxes | (20,104 | ) | (17,567 | ) | (53,537 | ) | (43,080 | ) | |||||||
| Income tax expense | — | — | — | (4,444 | ) | ||||||||||
| Net loss | $ | (20,104 | ) | $ | (17,567 | ) | $ | (53,537 | ) | $ | (47,524 | ) | |||
| Net loss per common share | |||||||||||||||
| Basic and diluted | $ | (0.12 | ) | $ | (0.12 | ) | $ | (0.32 | ) | $ | (0.32 | ) | |||
| Weighted average number of common shares | |||||||||||||||
| Basic and diluted | 167,512,708 | 150,995,191 | 165,085,243 | 149,385,999 | |||||||||||
UNAUDITED CONDENSED CONSOLIDATED BALANCE SHEETS
(in thousands)
| September 30, 2023 | December 31, 2022 | ||||
| Cash, cash equivalents and marketable securities, current | $ | 134,180 | $ | 146,913 | |
| Accounts receivable and other current assets | 7,427 | 4,226 | |||
| Total current assets | 141,607 | 151,139 | |||
| Property and equipment, net of accumulated depreciation | 5,033 | 5,070 | |||
| Investments in marketable securities, non-current | 10,496 | 37,363 | |||
| Right of use asset | 1,502 | 1,744 | |||
| Other non-current assets | 3 | 103 | |||
| Total assets | $ | 158,641 | $ | 195,419 | |
| Accounts payable and accrued liabilities | $ | 9,806 | $ | 16,029 | |
| Deferred license revenue, current | 12,106 | 16,456 | |||
| Lease liability, current | 412 | 372 | |||
| Total current liabilities | 22,324 | 32,857 | |||
| Liability related to sale of future royalties | 8,110 | 10,365 | |||
| Deferred license revenue, non-current | — | 5,999 | |||
| Contingent consideration | 7,373 | 7,531 | |||
| Lease liability, non-current | 1,497 | 1,815 | |||
| Total stockholders’ equity | 119,337 | 136,852 | |||
| Total liabilities and stockholders’ equity | $ | 158,641 | $ | 195,419 | |
UNAUDITED CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS
(in thousands)
| Nine Months Ended September 30, | |||||||
| 2023 | 2022 | ||||||
| Net loss | $ | (53,537 | ) | $ | (47,524 | ) | |
| Non-cash items | 4,613 | 3,429 | |||||
| Change in deferred license revenue | (10,349 | ) | 25,463 | ||||
| Other changes in working capital | (9,371 | ) | 266 | ||||
| Net cash (used in) operating activities | (68,644 | ) | (18,366 | ) | |||
| Net cash provided by (used in) investing activities | 28,548 | (87,624 | ) | ||||
| Issuance of common shares pursuant to Share Purchase Agreement | — | 10,973 | |||||
| Issuance of common shares pursuant to the Open Market Sale Agreement | 26,000 | 9,241 | |||||
| Cash provided by other financing activities | 840 | 516 | |||||
| Net cash provided by financing activities | 26,840 | 20,730 | |||||
| Effect of foreign exchange rate changes on cash and cash equivalents | 11 | (18 | ) | ||||
| Decrease in cash and cash equivalents | (13,245 | ) | (85,278 | ) | |||
| Cash and cash equivalents, beginning of period | 30,776 | 109,282 | |||||
| Cash and cash equivalents, end of period | 17,531 | 24,004 | |||||
| Investments in marketable securities | 127,145 | 166,150 | |||||
| Cash, cash equivalents and marketable securities, end of period | $ | 144,676 | $ | 190,154 | |||
Conference Call and Webcast Today
Arbutus will hold a conference call and webcast today, Tuesday, November 7, 2023, at 8:45 AM Eastern Time to provide a corporate update. To dial-in for the conference call by phone, please register using the following link: Registration Link. A live webcast of the conference call can be accessed through the Investors section of Arbutus' website at www.arbutusbio.com.
An archived webcast will be available on the Arbutus website after the event.
About imdusiran (AB-729)
Imdusiran is an RNA interference (RNAi) therapeutic specifically designed to reduce all HBV viral proteins and antigens including hepatitis B surface antigen, which is thought to be a key prerequisite to enable reawakening of a patient’s immune system to respond to the virus. Imdusiran targets hepatocytes using Arbutus’ novel covalently conjugated N-Acetylgalactosamine (GalNAc) delivery technology enabling subcutaneous delivery. Clinical data generated thus far has shown single and multiple doses of imdusiran to be generally safe and well-tolerated, while also providing meaningful reductions in hepatitis B surface antigen and hepatitis B DNA. Imdusiran is currently in multiple Phase 2a clinical trials.
About AB-101
AB-101 is our oral PD-L1 inhibitor candidate that we believe will allow for controlled checkpoint blockade while minimizing the systemic safety issues typically seen with checkpoint antibody therapies. Immune checkpoints such as PD-1/PD-L1 play an important role in the induction and maintenance of immune tolerance and in T-cell activation. Preclinical data generated thus far indicates that AB-101 mediates re-activation of exhausted HBV-specific T-cells from cHBV patients. We believe AB-101, when used in combination with other approved and investigational agents, could potentially lead to a functional cure in patients chronically infected with HBV. AB-101 is currently being evaluated in a Phase 1a/1b clinical trial. We have identified compounds in our internal PD-L1 portfolio that could also be used in oncology indications.
About HBV
Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV). HBV can cause chronic infection which leads to a higher risk of death from cirrhosis and liver cancer. Chronic HBV infection represents a significant unmet medical need. The World Health Organization estimates that over 290 million people worldwide suffer from chronic HBV infection, while other estimates indicate that approximately 2.4 million people in the United States suffer from chronic HBV infection. Approximately 820,000 people die every year from complications related to chronic HBV infection despite the availability of effective vaccines and current treatment options.
About Arbutus
Arbutus Biopharma Corporation (Nasdaq: ABUS) is a clinical-stage biopharmaceutical company leveraging its extensive virology expertise to identify and develop novel therapeutics with distinct mechanisms of action, which can be combined to provide a functional cure for patients with chronic hepatitis B virus (cHBV). We believe the key to success in developing a functional cure involves suppressing HBV DNA, reducing surface antigen, and boosting HBV-specific immune responses. Our pipeline of internally developed, proprietary compounds includes an RNAi therapeutic, imdusiran (AB-729) and an oral PD-L1 inhibitor, AB-101. Imdusiran has generated meaningful clinical data demonstrating an impact on both surface antigen reduction and reawakening of the HBV-specific immune response. Imdusiran is currently in two Phase 2a combination clinical trials. AB-101 is currently being evaluated in a Phase 1a/1b clinical trial. Additionally, we have identified compounds in our internal PD-L1 portfolio that could also be used in oncology indications. 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 future development plans for our product candidates; our program updates; our belief that checkpoint inhibitors may play a key role in antiviral immune tolerance in cHBV; the expected cost, timing and results of our clinical development plans and clinical trials with respect to our product candidates; our expectations with respect to clinical trial design and the release of data from our clinical trials and the expected timing thereof; our expectations and goals for our collaborations with third parties and any potential benefits related thereto; the potential for our product candidates to achieve success in clinical trials; our expected financial condition, including the anticipated duration of cash runways and timing regarding needs for additional capital and our expected management changes.
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 patent litigation matters.
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: the risk that the program updates may not materially extend the cash runway and may create a distraction or uncertainty that may adversely affect our operating results, business, or investor perceptions; 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 product 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; uncertainties associated with litigation generally and patent litigation specifically; it may take considerable time and expense to resolve the clinical hold that has been placed on AB-101 by the FDA, and no assurance can be given that the FDA will remove the clinical hold; Arbutus and its collaborators may never realize the expected benefits of the collaborations; and market shifts may require a change in strategic focus; and risks related to the sufficiency of Arbutus’ cash resources and its ability to obtain adequate financing in the future for its foreseeable and unforeseeable operating expenses and capital expenditures.
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
Lisa M. Caperelli
Vice President, Investor Relations
Phone: 215-206-1822
Email: lcaperelli@arbutusbio.com
Exhibit 99.2
NASDAQ: ABUS www.arbutusbio.com November 7, 2023 Corporate Presentation © 2023 Arbutus Biopharma, Inc.
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 : the potential market opportunity for HBV ; Arbutus’ ability to meet a significant unmet medical need ; the sufficiency of Arbutus’ cash and cash equivalents for the anticipated durations ; the expected cost, timing and results of Arbutus’ clinical development plans and clinical trials, including its clinical collaborations with third parties ; the potential for Arbutus’ product candidates to achieve their desired or anticipated outcomes ; Arbutus’ expectations regarding the timing and clinical development of Arbutus’ product candidates, including its articulated clinical objectives ; the timeline to a combination cure for HBV ; Arbutus’ expectations regarding its technology licensed to third parties ; the expected timing and payments associated with strategic and/or licensing agreements ; the patent infringement lawsuits ; 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 pre - clinical 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 patent litigation matters . 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 ; uncertainties associated with litigation generally and patent litigation specifically ; market shifts may require a change in strategic focus ; and the parties may never realize the expected benefits of the collaborations . 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 . 2 © 2023 Arbutus Biopharma, Inc.
Our Strategy for Value Creation Leverage the proven track record of success established with our team's expertise in understanding and treating viral infections by discovering and developing a differentiated pipeline of therapies targeting chronic HBV. Develop a combination therapy that includes antivirals and immunologics to provide a finite duration treatment for people with cHBV that results in >20% functional cure rate. HBV: Hepatitis B Virus | cHBV: chronic HB V 3 © 2023 Arbutus Biopharma, Inc.
Investment Highlights Strong financial position Indications with significant unmet medical need & large market opportunities Patented LNP technology Portfolio of internally discovered assets with distinct MOAs Lead HBV compound – imdusiran (AB - 729) RNAi therapeutic in multiple Phase 2a combination clinical trials Team with virology expertise and proven track record Focused on developing a functional cure for HBV Cash runway into Q1 2026 Data shows imdusiran is generally safe and well - tolerated and has shown meaningful suppression of HBsAg while on - or off - treatment RNAi therapeutic PD - L1 inhibitor Receiving licensing royalties arising from Alnylam’s Onpattro ® and seeking damages for Moderna & Pfizer/BioNTech COVID - 19 vaccine sales Discovered, developed & commercialized multiple drugs MOA: Mechanism of Action | PD - L1: Programmed death - ligand 1 | HBsAg: Hepatitis B surface antigen 4 © 2023 Arbutus Biopharma, Inc.
Pipeline AB - 101 cHBV NA: Nucleoside Analogue 5 Imdusiran (AB - 729) cHBV AB - 729 - 201 Combo trial (imdusiran + Peg - IFN α - 2a + NA) AB - 729 - 202 Combo trial (imdusiran + vaccine + NA +/ - checkpoint inhibitor) AB - 729 - 001 single - ascending dose / multiple - ascending dose RNAi Therapeutic PD - L1 Inhibitor AB - 101 - 001 single - and multiple - ascending dose © 2023 Arbutus Biopharma, Inc. Lead Optimization IND Enabling Phase 1 Phase 2 Phase 3 Marketed
HBV Overview Life - threatening liver infection caused by hepatitis B virus (HBV) Transmitted through body fluids and from mother to child Long - term chronic infection ( cHBV ) leads to higher risk of cirrhosis and/or liver cancer Cause & Symptoms Diagnosis HBsAg detection Additional biomarkers necessary to determine stage of disease Treatments NA therapy – lifelong daily therapy, aimed at reducing HBV DNA and risk of cirrhosis and/or HCC Peg - IFN α – administered weekly; poorly tolerated <5% of patients achieve functional cure Rationale Need for finite and more efficacious HBV treatments that further improve long - term outcomes and increase functional cure rate Combination therapy with different MOAs will be required to reduce HBsAg, suppress HBV DNA, and boost immune system Sources for all data on slide: 1 Hepatitis B Fact Sheet, WHO https://www.who.int/news - room/fact - sheets/detail/hepatitis - b ; Hep B Foundation link https://www.hepb.org/what - is - hepatitis - b/what - is - hepb/facts - and - figures/ ; Kowdley et al. Hepatology (2012) Prevalence of Chronic Hepatitis B Among Foreign - Born Persons Living in the US by Country of Origin 2 Pegasys , PEG - Intron, Baraclude and Viread Package Inserts HBsAg : HBV Surface Antigen | HCC: Hepatocellular carcinoma 6 © 2023 Arbutus Biopharma, Inc.
Africa 60M E Mediterranean 21M SE Asia 39M W Pacific 115M EU 15M Americas 7M ~820k people die every year as a consequence despite the availability of effective vaccines and antivirals. people are chronically infected with HBV, globally. >290M >290M Chronic HBV Sources: https://www.who.int/news - room/fact - sheets/detail/hepatitis - b https://www.hepb.org/what - is - hepatitis - b/what - is - hepb/facts - and - figures/ HBV Presents a Significant Unmet Medical Need 30M 6.6M 2.3% Treated Low due to sub - optimal SOC cure rate and asymptomatic nature of disease. 10.5% Diagnosed 2M USA 15M Europ e 90M China 7 SOC: Standard of Care © 2023 Arbutus Biopharma, Inc.
Suppress Reduce Boost Viral DNA and cccDNA Pool Viral Antigen - HBsAg Host Immune System Leading to an HBV Cure 3 - Pronged Approach to Therapeutic Success Therapeutic success will require a combination of agents with complementary MOAs. Suppress HBV DNA Reduce viral antigens Boost host immune response 8 NA RNAi RNAi RNAi PD - L1 Inhibitor Interferon Therapeutic Vaccines © 2023 Arbutus Biopharma, Inc.
9 RNAi Therapeutic
Proprietary GalNAc - conjugate delivery technology provides liver targeting and enables subcutaneous dosing Single trigger RNAi agent targeting all HBV transcripts Inhibits HBV replication and lowers all HBV antigens Pan - genotypic activity across HBV genotypes Demonstrated complementarity with other agents Actively targets the liver Active against cccDNA derived and integrated HBsAg transcripts Clean profile in long term preclinical safety studies RNAi Therapeutic Imdusiran GalNAc n Linker Polymerase, Core Ag, eAg , pgRNA sAg sAg HBx 10 © 2023 Arbutus Biopharma, Inc.
AB - 729 - 001: Phase 1a/1b Clinical Trial with Imdusiran HBeAg: HBV E antigen | TDF: tenofovir disoproxil fumarate Part 3: Multiple Ascending Dose in cHBV Patients E: 60mg Q4W HBV DNA - F: 60mg Q8W HBV DNA - G: 90mg Q8W + TDF HBV DNA+ I: 90mg Q8W HBV DNA - J: 90mg Q12W HBV DNA - K: 90mg Q8W HBV DNA - , HBeAg+ only Single - ascending dose Imdusiran monotherapy conclusions: • Robust HBsAg declines across all cohorts • HBV DNA declines in HBV DNA+ patients Part 1 & 2: 11 Data presented at EASL 2022 © 2023 Arbutus Biopharma, Inc.
AB - 729 - 001: Robust HBsAg Declines Irrespective of Imdusiran Dose, Dosing Schedule, HBeAg or HBV DNA Status Mean (SE) Baseline and Δ log 10 HBsAg by Visit Data shown as mean (SE) log 10 IU/mL; minimum of 5 subjects/timepoint. Last imdusiran (AB - 729) dose Cohort E: Week 44, Cohorts F, I, G, K: Week 40, Cohort J: Week 36; HBsAg Assay LLOQ = 0.07 IU/mL; *N=6; # N=5 12 All Cohorts achieved at least a - 1.8 log 10 decline in mean HBsAg at the end of the treatment period (Week 48) Mean HBsAg levels remained below baseline values at Follow Up Week 48 There were no significant differences in mean HBsAg declines between the 60 mg and 90 mg doses or between different dosing intervals Data presented at Global Hepatitis Summit 2023 © 2023 Arbutus Biopharma, Inc. HBV DNA+ HBV DNA - Visit Cohort G (N=7) Cohort K (N=7) Cohort J (N=7) Cohort I (N=6) Cohort F (N=7) Cohort E (N=7) 3.14 (0.14) 3.23 (0.14) 3.37 (0.28) 3.36 (0.23) 3.53 (0.17) 3.51 (0.20) Baseline - 1.56 (0.32) - 1.63 (0.39) - 1.06 (0.31) - 1.30 (0.19) - 1.02 (0.11) - 1.10 (0.15) Treatment Week 12 - 1.82 (0.29) - 1.99 (0.35) - 1.56 (0.25) - 1.79 (0.22) - 1.57 (0.09) - 1.84 (0.16) Treatment Week 24 - 2.05 (0.31) - 2.57 (0.61) - 1.80 (0.41) - 1.91 (0.32) - 1.90 (0.14) - 1.89 (0.18) Treatment Week 48 - 1.50 (0.13) - 2.38 (0.75) - 1.52 (0.40) - 1.42 (0.26) - 1.59 (0.23) - 1.74 (0.20) Follow Up Week 12 - 1.53 (0.29) - 1.82 (0.63) - 1.49 (0.35) - 1.37 (0.39) - 1.26 (0.21) - 1.43 (0.18) Follow Up Week 24 - 1.10 (0.27) - 1.86 (0.70) - 1.04 (0.20) - 0.88 (0.33) - 1.01 (0.24) - 1.55 (0.56) Follow Up Week 48
Data presented at EASL 2022 and AASLD 2022 13 Change in HBsAg vs time AB - 729 - 001 : Robust & Sustained HBsAg Declines While On - or Off - Treatment with Imdusiran 33 of 41 patients had HBsAg < 100 IU/mL at some point during the trial 1 patient in Cohort E (baseline HBsAg = 583.5 IU/mL) who qualified but declined to participate in NA discontinuation seroconverted at Week 84 (HBsAg < LLOQ and HBsAb = 189 IU/mL at last visit); liver enzymes remained within normal limits. 2 patients in Cohort K reached HBsAg<LLOQ on multiple visits with detectable HBsAb levels Cohort I Cohort F Cohort E Cohort J Cohort G Cohort K © 2023 Arbutus Biopharma, Inc.
AB - 729 - 001 : Imdusiran Shows Low Levels of HBV Biomarkers Persisting in cHBV Patients While Off - Treatment 7 of 9 (78%) subjects remain off NA therapy for 44 - 64 weeks and all completed imdusiran treatment over 1½ years ago Most subjects have maintained low HBV DNA levels off treatment 14 Data presented at GHS 2023 * Patient 53 restarted NA therapy at Investigator’s request after the NA d/c FU W20 visit (pink shaded area). ** Patient 58 restarted therapy after the NA d/c FU W36 visit (pink shaded area) . © 2023 Arbutus Biopharma, Inc. Patient 46 Baseline HBsAg = 1392 IU/mL Patient 58** (Cohort G) NA retreatment Baseline HBsAg = 1397 IU/mL Patient 51 Patient 61 Baseline HBsAg = 2021 IU/mL HBsAg (IU/mL), ALT (U/L) HBV DNA (IU/mL) Patient 52 Baseline HBsAg = 1888 IU/mL Patient 59 (Cohort G) Baseline HBsAg = 1338 IU/mL Patient 60 (Cohort G) Baseline HBsAg = 1128 IU/mL Patient 56 (Cohort G) Baseline HBsAg = 277 IU/mL HBsAg remains between - 0.8 and - 1.6 log 10 IU/mL below baseline values NA discontinuation post - imdusiran treatment appears well tolerated with no ALT flares HBsAg (IU/mL), ALT (U/L) HBV DNA (IU/mL) Patient 53* NA retreatment Baseline HBsAg = 2368 IU/mL Baseline HBsAg = 6765 IU/mL
AB - 729 - 001 : Treatment with Imdusiran Reactivates HBV Specific Immunity in Some Patients 15 0 4 812162024283236404448525660 0 1 2 3 4 5 0 20 40 60 H B s A g ( L o g 1 0 I U / m L ) Patient 43 60 mg Q4W 0 4 8 1216202428323640444852 0 1 2 3 4 0 10 20 30 40 50 60 H B s A g ( L o g 1 0 I U / m L ) Patient 48 60 mg Q8W Upregulation of HBV - specific T - cell activation markers observed in all 7 patients assessed to date Two profiles of HBV - specific T cell IFN - γ responses observed Elevation between Wk 16 - 28 which coincides with nadir of HBsAg reduction *Elevation after imdusiran dosing completed, between Wk 48 - 60 Data presented at EASL 2022 Patient 42* 60 mg Q4W Imdusiran Increased HBV - Specific T - Cell Activation Imdusiran Decreased Exhausted T - Cells B a s e l i n e E O T W k 3 2 ^ F / U W k 5 6 B a s e l i n e E O T W k 3 2 ^ F / U W k 5 6 0 10 20 30 F r e q u e n c y ( % ) Patient 43 ^ Last on - treatment PBMC sample available prior to last dose at Wk 44 B a s e l i n e E O T W k 4 0 F / U W k 5 2 B a s e l i n e E O T W k 4 0 F / U W k 5 2 0 10 20 30 F r e q u e n c y ( % ) Patient 48 B a s e l i n e E O T W k 4 4 F / U W k 6 0 B a s e l i n e E O T W k 4 4 F / U W k 6 0 0 10 20 30 F r e q u e n c y ( % ) Patient 42 © 2023 Arbutus Biopharma, Inc.
AB - 729 - 001 Safety Summary Imdusiran is generally safe and well - tolerated after repeat dosing for up to 48 weeks No treatment - related SAEs or discontinuations due to AEs No treatment - related Grade 3 or 4 AEs No treatment - related Grade 3 or 4 laboratory abnormalities • Grade 1 and Grade 2 ALT elevations have improved or stabilized with continued treatment Injection site AEs were all Grade 1 (erythema, pain, bruising) No clinically meaningful changes in ECGs or vital signs After NA treatment discontinuation, no ALT flares have been observed 16 SAE: Serious Adverse Event | AE: Adverse Event © 2023 Arbutus Biopharma, Inc.
AB - 729 - 001 Clinical Trial Key Takeaways Imdusiran provided robust and comparable HBsAg declines regardless of dose, dosing interval, HBeAg or DNA status Discontinuation of both imdusiran and NA - therapy results in sustained reduction in HBsAg and HBV DNA in 7 of 9 patients Imdusiran was generally safe and well - tolerated after completing dosing in 41 patients Imdusiran results in HBV - specific T - cell immune restoration and decrease of exhausted T - cells in some patients 17 * Data previously presented © 2023 Arbutus Biopharma, Inc.
Phase 2a POC Clinical Trial Imdusiran in combination with ongoing NA therapy and short courses of Peg - IFN α - 2 a in cHBV patients AB - 729 - 201: Follow - up (24 - weeks) Imdusiran + NA + IFN (n=12) NA + IFN (n=12) Imdusiran +NA+IFN (n=8) NA + IFN (n=8) Imdusiran + NA (60mg Q8W) n=43 HBeAg - Randomize Follow - up (24 - weeks) 1 52 28 24 40 Weeks POC: Proof of Concept *Data presented at EASL 2023 Primary objective : evaluate safety and tolerability of imdusiran in combination with Peg - IFNa - 2a in patients with NA - suppressed cHBV Preliminary results*: treatment was generally well tolerated with continued HBsAg declines in some patients during the IFN treatment period • Mean HBsAg decline during lead - in phase was 1.6 log 10 at week 24 of treatment • 93% of patients (38 of 41 randomized) had HBsAg levels <100 IU/mL during treatment period • 4 patients reached HBsAg levels <LLOQ during IFN treatment After 24 - weeks of follow - up, patients are assessed to stop NA therapy. Those patients that stop NA therapy will be followed for an additional 48 weeks. Multi - center, open - label Phase 2a 18 © 2023 Arbutus Biopharma, Inc.
Phase 2a POC Clinical Trial POC Phase 2a clinical trial evaluating imdusiran in combination with Barinthus ’ (formerly Vaccitech ) immunotherapeutic, VTP - 300, with or without low dose nivolumab, and a NA AB - 729 - 202: Primary objective: evaluate safety and reactogenicity of imdusiran followed by VTP - 300 or placebo At Week 48 all participants who are eligible to discontinue NA therapy will be followed for an additional 48 weeks Expanded the clinical trial to include an additional arm with nivolumab ( Opdivo ® ), and dosed first patient in this arm in the first half of 2023 Full rights retained by the Companies of their respective product candidates and all costs split equally 19 Follow - up (24 - 48 weeks) VTP - 300 + NA (n=20) NA + placebo (n=20) 1 Imdusiran + NA (60mg Q8W) n=40 Randomize Weeks Imdusiran + NA (60mg Q8W) n=20 24 VTP - 300 + NA + Nivo 1 48 26 24 Weeks 48 Follow - up (24 - 48 weeks) Preliminary data will be presented at AASLD © 2023 Arbutus Biopharma, Inc.
Strategic Collaboration Exclusive Licensing* and Strategic Partnership Develop, manufacture and commercialize imdusiran in mainland China, Hong Kong, Macau and Taiwan Imdusiran Upfront payment (received in 2022) $40M Equity investment (received in 2022) $15M Commercialization and milestone payments Up to $245M Tiered royalties on annual sales Double - digit up to low twenties % *ABUS retains the non - exclusive right to develop and manufacture in the Qilu territory for exploiting AB - 729 in the rest of the world Deal economics for Arbutus: Qilu Pharmaceutical: One of the leading pharmaceutical companies in China, provides development, manufacturing, and commercialization expertise to this partnership China 20 © 2023 Arbutus Biopharma, Inc.
Oral PD - L1 Inhibitor 21
AB - 101: Oral PD - L1 Inhibitor for HBV Immune Reactivation PD - 1: Programmed death ligand protein | Abs: Antibodies Currently in a Phase 1a/1b clinical trial Rationale • HBV immune tolerance is a critical driver of cHBV infection • PD - 1:PD - L1 checkpoint axis plays a key role in immune tolerization in cHBV • PD - L1 expression upregulated during HBV infection • PD - 1 upregulated on HBV - specific T - and B - cells • Inhibition associated with HBsAg loss in some cHBV patients AB - 101 • Blocks PD - L1/PD - 1 interaction at sub - nM concentrations • Activates HBV - specific immune responses in T - cells from cHBV patients in vitro • Novel MOA identified • Demonstrates a robust checkpoint mediated in vivo effect • Improves HBV - specific T - and B - cell responses ex vivo Small - Molecule Inhibitor Approach • Allows controlled checkpoint blockade • Enables oral dosing • Designed to reduce systemic safety issues seen with Abs 22 © 2023 Arbutus Biopharma, Inc.
AB - 101: Small - Molecule Oral PD - L1 Inhibitor for HBV AB - 101 is highly potent and activates HBV specific immune cells from chronic HBV patients AB - 101 reinvigorates HBV - specific cHBV patient T - cells PBMCs N= cells from 9 cHBV patients *p< - 0.05 PBMC: P eripheral Blood Mononuclear Cells PDL1 * Inactive AB - 101 * 0 3 2 1 IFN - y Fold Increase Over HBV peptide alone 23 © 2023 Arbutus Biopharma, Inc. Once daily oral administration of AB - 101 resulted in profound tumor reduction Study Day MC38 Tumor Mouse Model Tumor Volume (mm 3 ) Data presented at EASL 2022
24 © 2023 Arbutus Biopharma, Inc. Part 1: SAD (n=8/cohort – 6:2) 1C: Dose 3 1B: Dose 2 1A: Dose 1 Part 2: MAD (n=10/cohort – 8:2) 2A: Do se ≤ dose tested in Part 1; interval TBD 2B: Dose/interval TBD 3A: Dose ≤ dose tested in Part 2; interval TBD x 28d 3B: Dose/interval TBD x 28d 3C: Dose/interval TBD x 28d AB - 101 - 001: Phase 1a/1b Clinical Trial with AB - 101 Parts 1 & 2 – Healthy Subjects Part 3 – cHBV Patients (n=12/cohort – 10:2) Virally suppressed Additional optional dose panels may be used.
2023 Key Milestones Cash balance * of $145M as of Sept 30, 2023, cash runway into Q1 2026; 2023 net cash burn of between $90M and $95M *Consists of cash, cash equivalents and marketable securities 25 Anticipated Timing 2023 Milestone 1H Imdusiran: Dose f irst patient in the imdusiran+VTP - 300+Nivo arm of the ongoing Phase 2a Vaccitech trial 1H Imdusiran: Preliminary IFN data from patients in the AB - 729 - 201 clinical trial 1H Imdusiran: Follow - up off - treatment data from AB - 729 - 001 clinical trial Q4 Imdusiran: Preliminary data from Phase 2a POC clinical trial with imdusiran+VTP - 300+NA therapy 2H AB - 101: Initiate single - ascending dose portion of Phase 1 clinical trial in healthy subjects © 2023 Arbutus Biopharma, Inc.
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