SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
Pursuant to Section 13 or 15(d)
of The Securities Exchange Act of 1934
Date of Report (Date of earliest event reported)
(Exact name of registrant as specified in its charter)
(State or other jurisdiction
(Address of principal executive offices, including zip code)
(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 (see General Instruction A.2. below):
Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
Pre-commencement communications 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
Name of each exchange
on which registered
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
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. ☐
|Item 8.01|| |
Continuing Progress of the COMET Clinical Development Program for Sotrovimab
On June 21, 2021, Vir Biotechnology, Inc. (the “Company”) and GlaxoSmithKline plc (“GSK”) issued a press release announcing final, confirmatory results from the Phase 3 COMET-ICE (COVID-19 Monoclonal antibody Efficacy Trial – Intent to Care Early) trial demonstrating that sotrovimab, an investigational SARS-CoV-2 monoclonal antibody, significantly reduced the risk of hospitalization or death among high-risk adult outpatients with mild-to-moderate COVID-19.
The primary efficacy analysis of all 1,057 patients in the COMET-ICE trial demonstrated a 79% reduction (adjusted relative risk reduction) (p<0.001) in hospitalization for more than 24 hours or death due to any cause, by Day 29 compared to placebo, meeting the primary endpoint of the trial.
The number of patients in the trial who were hospitalized for >24 hours for acute management of any illness or death from any cause at Day 29 was six patients in the sotrovimab arm (1%), versus 30 patients in the placebo arm (6%). In the sotrovimab arm, it is possible that half of those patients who were hospitalized were for reasons other than progression of COVID-19 (e.g., small bowel obstruction, lung cancer and diabetic foot ulcer); this was not the case for patients in the placebo arm. In the safety analysis, 1,037 participants were followed through at least 29 days. The most common adverse events observed in the sotrovimab treatment group in COMET-ICE were rash (1%) and diarrhea (2%), all of which were Grade 1 (mild) or Grade 2 (moderate). No other treatment-emergent adverse events were reported at a higher rate with sotrovimab compared to placebo. The Company and GSK plan to submit the full COMET-ICE data set to a peer-reviewed journal for publication.
The National Institutes of Health (“NIH”) recently updated its guidelines regarding the emergency use authorizations of anti-SARS-CoV-2 monoclonal antibodies for the treatment of COVID-19 in the U.S. to recommend the use of sotrovimab for non-hospitalized patients with mild-to-moderate COVID-19 who are at high risk of clinical progression. The guidelines note that the target binding site of sotrovimab is in a region of the virus that does not overlap with the binding site location of key mutations in current variants of concern and interest. These guidelines were based upon an interim analysis of 583 patients in the COMET-ICE trial, which was stopped early in March 2020 by an independent data monitoring committee because interim results demonstrated evidence of sotrovimab’s clinical efficacy. The interim study results demonstrated an 85% (p=0.002) reduction in hospitalization for more than 24 hours or death in those receiving sotrovimab compared to placebo, the primary endpoint of the trial.
These data have informed global regulatory reviews to date, including the positive scientific opinion issued by the European Medicines Agency’s (“EMA”) Committee for Human Medicinal Products (“CHMP”) under Article 5(3) of Regulation 726/2004, as well as the Emergency Use Authorization (“EUA”) granted by the U.S. Food and Drug Administration (“FDA”).
The Company and GSK are actively working with government agencies around the world to make sotrovimab available to patients in need of treatment. The Company and GSK plan to submit a Biologics License Application to the FDA in the second half of 2021. The EMA has started a rolling review of data on sotrovrimab that will continue until enough evidence is available to support the filing of a formal marketing authorization application. The Company and GSK also announced that their strategic manufacturing network is enabling the manufacture of approximately two million doses to support emergency supply in the first year following EUA, with approximately 450,000 doses on hand.
The Company and GSK also announced continued progress with the robust COMET clinical development program, which aims to provide clinical evidence from several studies over the course of the next year.
COMET-PEAK, a pharmacokinetic study in outpatients with mild-to-moderate COVID-19 investigating intramuscular (IM) administration of sotrovimab, is near completion and initial data is expected in second half of 2021.
COMET-TAIL has been initiated. This is a Phase 3 study evaluating the role of IM-administered sotrovimab for the early treatment of mild-to-moderate COVID-19 in high-risk non-hospitalized adult and pediatric patients (12 years of age and older). Data are anticipated in the first half of 2022.
A prophylaxis study is planned in uninfected immunocompromised adults to determine whether IM-administered sotrovimab can prevent symptomatic COVID-19 infection.
New Clinical Data from Ongoing Trials of VIR-2218 and VIR-3434
On June 25, 2021, the Company issued a press release announcing new data from its ongoing Phase 2 clinical trials of VIR-2218 and ongoing Phase 1 studies of VIR-3434 in patients with chronic hepatitis B virus (“HBV”) infection. The results, which demonstrate positive safety findings plus a reduction in hepatitis B surface antigen (“HBsAg”) for both compounds, were presented in two oral and two poster presentations at the European Association for the Study of the Liver International Liver Congress 2021.
In summary, data presented this week demonstrate the promising safety profile and potential durable response of VIR-2218, an investigational small interfering ribonucleic acid (“siRNA”) that mediates RNA interference (“RNAi”), through 48 weeks. In a separate analysis evaluating VIR-2218 in combination with pegylated interferon alfa (“PEG-IFN-α”) for 12 weeks, a more rapid and substantial HBsAg decline was observed in the co-administration cohort compared to VIR-2218 alone. The treatment regimen resulted in no new safety signals.
Additionally, two new analyses from an ongoing Phase 1 trial of VIR-3434 showed no safety signals in healthy volunteers dosed with up to 3,000 mg, and a rapid reduction in HBsAg levels one week after subcutaneous administration of this investigational HBV-neutralizing monoclonal antibody, which has been Fc engineered to include the XX2 “vaccinal mutation,” allowing it to potentially function as a T cell vaccine.
VIR-2218 Key Data
Results from a Phase 2 multiple-ascending dose trial of VIR-2218 in 32 patients with chronic HBV infection evaluating the safety and antiviral activity of two doses of VIR-2218 (20 to 200 mg) administered subcutaneously four weeks apart demonstrate:
Dose-dependent reductions in HBsAg through 48 weeks in both trial participants with hepatitis B e antigen (“HBeAg”), a marker of actively replicating HBV, and those without.
Of the 12 participants who received the 100 mg or 200 mg dose, four participants experienced sustained HBsAg reductions of >1 log10 IU/mL and absolute HBsAg levels below 100 IU/mL through Week 48.
Treatment with VIR-2218 also achieved dose-related reductions in other viral biomarkers; one patient receiving 200 mg experienced HBeAg loss at Week 24 and anti-HBe seroconversion at Week 16 that was sustained through Week 48.
Adverse events were mild, and no dose-dependent changes in post-treatment ALT levels (a signal of liver damage) occurred. No trial participants discontinued treatment.
In a separate ongoing Phase 2 trial, 47 adult patients with chronic HBV infection were assigned to receive subcutaneously injected VIR-2218 alone or in combination with PEG-IFN-α. Preliminary results through Week 12 of the treatment period demonstrate:
VIR-2218 alone and in combination with PEG-IFN-α were associated with HBsAg reductions of >1 log10 IU/mL by Week 12.
Co-administration of VIR-2218 with PEG-IFN-α (“Cohort 3”) resulted in a more rapid and substantial HBsAg decline compared to VIR-2218 alone.
In Cohort 3, the mean HBsAg decline from baseline was 2.0 log10 IU/mL at Week 12 and 0.6 log10 IU/mL greater than in the two cohorts evaluating VIR-2218 alone.
In published studies, PEG-IFNα alone in virally suppressed patients was associated with £ 0.25 log10 IU/mL HBsAg decline, on average, over the first 12 weeks.
No treatment-related grade ³3 treatment-emergent adverse events or serious adverse events were reported with VIR-2218 alone or in combination with PEG-IFN-α, and the combination did not appear to increase the known side effects of PEG-IFN-α.
VIR-3434 Key Data
Results from a Phase 1 trial evaluating VIR-3434 in 40 virally suppressed patients with chronic HBV infection who were randomized to receive a single low dose of either 6 mg or 18 mg for four weeks demonstrate:
Treatment with VIR-3434 resulted in rapid >1 log10 IU/mL reductions in HBsAg, with the largest reductions (>1.5 log10 IU/mL) observed in the 18 mg cohort; maximum reductions were generally observed within one week.
No new safety signals were identified with single doses of VIR-3434; all adverse events were grade 1 or 2.
No significant changes in liver-related laboratory parameters or clinically significant changes in ALT or other liver-related laboratory parameters were reported.
In a separate Phase 1 trial in 40 healthy adult volunteers evaluating single doses of up to 3,000 mg of VIR-3434 administered subcutaneously or intravenously, results demonstrate:
Subcutaneous administration of VIR-3434 showed favorable pharmacokinetic properties, with VIR-3434 remaining in the serum for 24 weeks.
No new safety signals were identified; specifically, no grade 3/4 adverse events, serious adverse events or adverse events leading to trial discontinuation were reported.
Sotrovimab Variant Update
Data from in vitro studies, published in bioRxiv has been updated to include new in vitro data demonstrating that sotrovimab retains activity against the following variants: Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), Epsilon (B.1.427/B.1.429), Gamma (P.1), Iota (B.1.526) and Kappa (B.1.617.1), as well as a new variant from Bristol (B.1.1.7+E484K) and the new variant from Cameroon (B.1.619), which encodes both N440K and E484K mutations that may lead to reduced activity for other antibody products. The Company and GSK are continuing to evaluate the ability of sotrovimab to maintain activity against new and emerging variants through in vitro studies. The clinical impact of this in vitro variants data is not yet known.
EASL ILC 2021 Hepatitis B Data Presentation
On June 25, 2021, the Company posted an EASL ILC 2021 Hepatitis B data presentation to its website. A copy of the presentation is attached as Exhibit 99.1.
This Current Report on Form 8-K contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “may,” “will,” “plan,” “potential,” “aim,” “promising” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These forward-looking statements are based on the Company’s expectations and assumptions as of the date of this Current Report on Form 8-K. Forward-looking statements contained in this Current Report on Form 8-K include, but are not limited to, statements regarding the final data from the COMET-ICE trial, NIH guidelines recommending the use of sotrovimab in the treatment of COVID-19, the initiation of the Company’s COMET-TAIL clinical trial, the clinical development program for sotrovimab, the Company’s capacity to manufacture and supply sotrovimab, the ability of sotrovimab to treat and/or prevent COVID-19, the ability of sotrovimab to maintain activity against circulating variants of concern, statements regarding clinical data from the Company’s ongoing trials of VIR-2218 and VIR-3434, timing of the Phase 2 trial of VIR-3434 in combination with VIR-2218, the ability of VIR-2218 and VIR-3434 (as monotherapies or combination therapies) to treat and/or prevent chronic HBV infection, and statements related to regulatory authorizations and approvals, including plans and discussions with the FDA, EMA and other global regulators. Many factors may cause differences between current expectations and actual results, including unexpected safety or efficacy data observed during preclinical or clinical studies, challenges in the treatment of hospitalized patients, difficulties in collaborating with other companies or government agencies, challenges in accessing manufacturing capacity, successful development and/or commercialization of alternative product candidates by the Company’s competitors, changes in expected or existing competition, delays in or disruptions to the Company’s business or clinical trials due to the COVID-19 pandemic, geopolitical changes or other external factors, and unexpected litigation or other disputes. Other factors that may cause actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in the Company’s filings with the U.S. Securities and Exchange Commission, including the section titled “Risk Factors” contained therein. Except as required by law, the Company assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.
|Item 9.01|| |
Financial Statements and Exhibits.
|99.1||Presentation, dated June 25, 2021.|
|104||Cover Page Interactive Data File (embedded within the Inline XBRL document)|
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.
|VIR BIOTECHNOLOGY, INC.|
|Date: June 28, 2021||By:|
|Chief Financial Officer|
Vir Biotechnology, Inc. EASL ILC 2021 Hepatitis B Data Call A WORLD WITHOUT INFECTIOUS DISEASE June 25, 2021 Exhibit 99.1
Legal Disclaimers © 2021 Vir Biotechnology, Inc. Forward-Looking Statements Statements in this presentation that are not statements of historical fact are forward-looking statements. Such forward-looking statements include, without limitation, statements regarding the expected success, cost, and timing of our research and clinical development plans and clinical trials, our goals with respect to the prophylaxis or treatment of COVID-19, HBV, influenza A and HIV, our objectives, strategy, technology platform and clinical trial designs, the potential benefits of our collaborations, and our ability to complete certain milestones. Words such as “believe,” “anticipate,” “plan,” “expect,” “intend,” “will,” “may,” “goal,” “potential” and similar expressions are intended to identify forward-looking statements, though not all forward-looking statements necessarily contain these identifying words. These forward-looking statements are based on the beliefs of the management of Vir Biotechnology, Inc. (the “Company”) as well as assumptions made by and information currently available to the Company. Such statements reflect the current views of the Company with respect to future events and are subject to known and unknown risks, including business, regulatory, economic and competitive risks, uncertainties, contingencies and assumptions about the Company, including, without limitation, risks inherent in developing the Company’s products and technologies, future results from the Company’s ongoing and planned clinical trials such as unexpected data or clinical site activation rates or clinical trial enrollment rates that are lower than expected, difficulties arising from our collaborations, challenges in accessing adequate manufacturing capacity, the Company’s ability to obtain adequate financing to fund its planned clinical trials and other expenses, statements related to regulatory authorizations and approvals, trends in the industry, changes in the competitive landscape, delays or disruptions due to the COVID-19 pandemic, the legal and regulatory framework for the industry, unexpected litigation or disputes and future expenditures. In light of these risks and uncertainties, the events or circumstances referred to in the forward-looking statements may not occur. The actual results may vary from the anticipated results and the variations may be material. Other factors that may cause the Company’s actual results to differ from current expectations are discussed in the Company’s filings with the U.S. Securities and Exchange Commission, including the section titled “Risk Factors” contained therein. These forward-looking statements should not be taken as forecasts or promises nor should they be taken as implying any indication, assurance or guarantee that the assumptions on which such forward-looking statements have been made are correct or exhaustive or, in the case of the assumptions, fully stated in this presentation. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date this presentation is given. Except as required by law, the Company undertakes no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise. The Company claims the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995 for all forward-looking statements. This presentation discusses product candidates that are under clinical study and which have not yet been approved for marketing by the U.S. Food and Drug Administration. No representation is made as to the safety or effectiveness of these product candidates for the use for which such product candidates are being studied. The trademarks included herein are the property of the owners thereof and are used for reference purposes only. Such use should not be construed as an endorsement of such products.
Disease Area Product Candidate Treatment/ Prophylaxis Pre-clinical Phase 1 Phase 2 Phase 3 Authorized Collaborator COVID-19 Sotrovimab* Treatment Sotrovimab + bamlanivimab Treatment Sotrovimab* Prophylaxis VIR-7832 Treatment HBV VIR-2218 Treatment VIR-2218 + PEG-IFN-⍺ Treatment VIR-3434 Treatment VIR-2218 + VIR-3434 Treatment VIR-2218 + TLR81 + PD-12 Treatment VIR-2218 + BRII-179 Treatment Influenza A VIR-2482 Prophylaxis HIV VIR-1111** Prophylaxis siRNA T cell Antibody Vir Clinical Development Pipeline Planned 2H:2021 start Planned 2H:2021 start *Sotrovimab (VIR-7831) IV formulation used in Phase 3 COMET-ICE trial; IM formulation currently in Phase 2 COMET-PEAK and COMET-TAIL trials, and pending in prophylaxis trial **Vaccine designed to establish proof of concept in Phase (Ph) 1 clinical trial to determine whether unique immune response observed in non-human primates can be replicated in humans; ultimately, any candidates we advance as a potential HIV vaccine will require modifications to VIR-1111 before further clinical development. 1: GS-9688 2: nivolumab †In the U.S., EUA received on 5/26/2021. In the EU, EMA positive opinion under Article 5(3) received on 5/21/2021. © 2021 Vir Biotechnology, Inc. U.S., EU†
Chronic HBV: Our Approach to Functional Cure We believe that chronic HBV (CHB) is a viral disease resulting in immune dysfunction We believe that chronic HBV infection results in immune dysfunction via the expression of a large amount of HBV antigens, which act to suppress the immune system We believe a functional cure for CHB results from regaining immunologic control We hypothesize that knocking down HBV antigens will remove the block on the immune system, and in the setting of an immune modulator, result in immune control © 2021 Vir Biotechnology, Inc.
Chronic HBV: HBV T cells become dysfunctional in infected mice Isogawa M, et al. PLoS Pathog 2013; 9(7):e1003490 © 2021 Vir Biotechnology, Inc. Transgenic HBV mouse Core-only expressing mouse HBV T cell HBV T cell
Chronic HBV: Reversal of Functional Cure Via Immunosuppression Seto W, et al. J Clin Oncol 2014; 32(33): 3736-43 © 2021 Vir Biotechnology, Inc. functionally cured patient (HbsAg < LLOQ) rituximab-containing chemotherapy + =
Vir’s Broad HBV Functional Cure Portfolio © 2021 Vir Biotechnology, Inc. VIR-2218 Phase 2 Data Potential Best-In-Class siRNA as “backbone” of therapy Substantial, Durable, and Dose Dependent Reduction of HBsAg through 48 weeks1 Ongoing / Planned Combination Trials Currently in Phase 2 PEG-IFN-⍺ Start Phase 2 trial in 2H:2021 VIR-3434 mAb Start Phase 2 trial in 2H:2021 GS-9688 TLR-8 agonist nivolumab PD-1 antagonist Currently in Phase 2 BRII-179 T cell vaccine Note: current and planned trials are/will be conducted in patients with chronic HBV on nucleotide/nucleoside reverse transcriptase inhibitors (NRTIs), which are standard of care treatment PEG-IFN: pegylated interferon alfa 1. Gane E, et al. Oral presentation at: The International Liver Congress – EASL; June 25, 2021; Virtual. Mean Change in Log10 HBsAg (IU/mL) Placebo 20 mg 50 mg 100 mg 200 mg Week
A Phase 1 study evaluating the neutralizing, vaccinal monoclonal antibody VIR-3434 in participants with chronic hepatitis B virus infection Safety and antiviral activity of VIR-2218, an X-targeting RNAi therapeutic, in participants with chronic hepatitis B infection: week 48 follow-up results Preliminary on-treatment data from a Phase 2 study evaluating VIR-2218 in combination with pegylated interferon alfa-2a in participants with chronic hepatitis B infection Preliminary pharmacokinetics and safety in healthy volunteers of VIR-3434, a monoclonal antibody for the treatment of chronic hepatitis B infection EASL ILC 2021: Vir Abstracts © 2021 Vir Biotechnology, Inc. PRESENTER Dr. Kosh Agarwal PRESENTER Prof. Edward Gane PRESENTER Prof. Dr. Man-Fung Yuen PRESENTER Dr. Sneha V. Gupta Oral Oral Poster Poster © 2021 Vir Biotechnology, Inc.
VIR-2218 20 mg Week HBsAg (IU/mL) VIR-2218 100 mg VIR-2218 50 mg VIR-2218 200 mg 10000 1000 10 100 10000 1000 10 100 0 4 8 12 16 20 24 28 32 36 40 44 48 0 4 8 12 16 20 24 28 32 36 40 44 48 Higher VIR-2218 Dose Levels Associated With a More Sustained Response through Week 48 With only 2 doses, at Week 0 and Week 4, four subjects achieved a sustained response through Week 48 In combination studies, VIR is exploring 3-6 doses of VIR-2218 Diversity of response being explored through immune biomarkers and biopsy/FNA study All participants on nucleos(t)ide reverse transcriptase inhibitors (NRTI) therapy HBsAg reduction < 1-log > 1-log Non-sustained > 1-log Sustained © 2021 Vir Biotechnology, Inc.
ESC+ Decreases Off-target Activity Enhanced stabilization chemistry plus (ESC+)* decreases off-target seed-mediated binding while maintaining on-target activity and is hypothesized to improve the hepatic safety profile. MRNA, microRNA; siRNA, small interfering RNA; UTR, untranslated region 1. Janas MM, et al. Nature Commun 2018;9:723; 2. Schlegel MK, et al. J Am Chem Soc 2017;139:8537-46. *Alnylam Pharmaceuticals, Inc. technology © 2021 Vir Biotechnology, Inc. 1,2 1,2
200 150 100 50 0 VIR-2218 20 mg Week Alanine Aminotransferase (U/L) HBeAg- HBeAg+ 200 150 100 50 0 0 4 8 12 16 20 24 28 32 36 40 44 48 VIR-2218 100 mg VIR-2218 50 mg 0 4 8 12 16 20 24 28 32 36 40 44 48 VIR-2218 200 mg No Dose-Dependent Changes in Post-Treatment ALT Levels through Week 48 No grade >1 ALT elevations*; no bilirubin >ULN No clinically relevant changes or trends in other lab parameters, vital signs, or ECGs All participants on nucleos(t)ide reverse transcriptase inhibitors (NRTI) therapy ALT, alanine transaminase; CTCAE, common terminology criteria for adverse events; ECG, electrocardiogram; ULN, upper limit of normal *Grade based on CTCAE v5.0 © 2021 Vir Biotechnology, Inc.
VIR-2218 With and Without PEG-IFNα Open-label study to evaluate the safety and antiviral activity of VIR-2218 alone or in combination with PEG-IFNα in non-cirrhotic, HBeAg-negative and positive adults with chronic HBV infection on NRTI therapy Participants will be followed for safety and antiviral endpoints for a minimum of 24 to 48 weeks after treatment; NRTI therapy may be discontinued if the pre-specified criteria are met to assess if functional cure is achieved The study is ongoing; preliminary safety and HBsAg through Week 12 are presented All participants on nucleos(t)ide reverse transcriptase inhibitors (NRTI) therapy HBsAg, hepatitis B surface antigen; NRTI, nucleos(t)ide reverse transcriptase inhibitors; PEG-IFNα, pegylated interferon alfa; SC, subcutaneous © 2021 Vir Biotechnology, Inc.
VIR-2218 with Pegylated Interferon Alfa-2a Mediated HBsAg Decreases from Baseline All participants on nucleos(t)ide reverse transcriptase inhibitors (NRTI) therapy. Study is ongoing, N values at each timepoint per cohort are indicated below the graph HBsAg, hepatitis B surface antigen; PEG-IFNα, pegylated interferon alfa 1. Marcellin P, et al. Gastroenterology. 2016;150(1):134-144; 2. Bourlière M, et al. Lancet Gastroenterol Hepatol. 2017;2(3):177-188; 3. Chi H, et al. J Infect Dis. 2017;215(7):1085-1093; 4. Farag MS, et al. Oral presentation at: The Liver Meeting of The American Association for the Study of Liver Diseases; November 11, 2019; Boston, MA, USA. © 2021 Vir Biotechnology, Inc. Co-administration of VIR-2218 with PEG-IFNα (Cohort 3) resulted in a more rapid and substantial HBsAg decline compared to VIR-2218 alone The mean HBsAg reduction in Cohort 3 was 0.6 log10 IU/mL greater than in Cohorts 1 and 2 at Week 12 In published studies, PEG-IFNα alone in virally suppressed patients was associated with ≤ 0.25 log10 IU/mL HBsAg decline, on average, over the first 12 weeks 1,2,3,4 Additional follow-up in Cohort 2 will provide insight into the antiviral effects of the combination when PEG-IFNα is administered following a 12-week lead-in period of VIR-2218 0.6 log
Early On-Treatment Data “We hypothesize that knocking down HBV antigens will remove the block on the immune system, and in the setting of an immune modulator, result in immune control” We believe that this VIR-2218+ PEG-IFNα data suggests that treatment with an siRNA could help unlock the potential of immunomodulators © 2021 Vir Biotechnology, Inc.
© 2021 Vir Biotechnology, Inc. VIR-3434: An Engineered Human Antibody Against HBsAg with Multiple Potential Mechanisms of Action cccDNA, covalently closed circular DNA; intDNA, integrated DNA; SVPs, subviral particles; HBsAg, hepatitis B surface antigen; PEG-IFNα, pegylated interferon alfa VIR-3434 incorporates Xencor’s XtendTM and other Fc technologies cccDNA intDNA Viral RNA Proteins DNA HBV Hepatocyte Virion SVPs Cross-presentation to and stimulation of T cells (vaccinal effect) 2 Clearance of HBsAg and delivery to dendritic cells 3 Inhibition of viral entry 1
VIR-3434-1002 Phase 1 Design In Part B, 8 participants per cohort were randomized 6:2 to receive a single dose of VIR-3434 or placebo by SC injection Blinded preliminary safety, tolerability, and HBsAg data up to 4 weeks post-dose are presented for Part B cohorts evaluating low doses of 6 mg and 18 mg All participants on nucleos(t)ide reverse transcriptase inhibitors (NRTI) therapy for ≥ 2 months 1. Cohort 1b (6 mg SC) enrolled participants with HBsAg < 1,000 IU/mL HBsAg, hepatitis B surface antigen; IV, intravenous; SC, subcutaneous, cccDNA, covalently closed ≤ 300 mg SC n=8 18 mg SC n=8 75 mg SC n=8 ≤ 900 mg SC n=8 (x 3 optional cohorts) 900 mg SC n=8 90 mg SC n=8 300 mg SC n=8 Part B SAD Virally Suppressed HBsAg <3,000 IU/mL1 6 mg SC1 n=8 Part A SAD Healthy Volunteers 3,000 mg IV n=8 900 mg IV n=8 ≤ 900 mg SC n=8 ≤ 900 mg SC n=8 Part C SAD Virally Suppressed Any HBsAg 18 mg SC n=8 Ongoing Complete Planned © 2021 Vir Biotechnology, Inc.
Preliminary PK of VIR-3434 After Single SC or IV Dose in Healthy Volunteers VIR-3434 was generally well tolerated in healthy volunteers following single doses of up to 3000 mg; AEs were generally mild, and no AEs led to study discontinuation The bioavailability and half-life following SC administration of VIR-3434 is estimated to be 76% and 25 days respectively Favorable PK properties of SC VIR-3434 and safety profile are supportive of continued development for the treatment of chronic HBV infection All participants on nucleos(t)ide reverse transcriptase inhibitors (NRTI) therapy *Includes a replacement subject HBsAg, hepatitis B surface antigen; IV, intravenous; SC, subcutaneous; AE, adverse event; SAE, serious adverse event © 2021 Vir Biotechnology, Inc. The most common reported AE across all groups was headache, which was observed in 10/41 (24.4%) participants Injection site reactions were reported in 6/41 (14.6%) participants, and all were grade 1 in severity except for a grade 2 AE of injection site erythema which resolved without intervention No grade 3/4 AEs, SAEs, or AEs leading to study discontinuation were observed No clinically significant laboratory abnormalities were observed Subjects with > 1 AE, n (%) VIR-3434 or Placebo 90mg SC n=9* 300 mg SC n=8 900 mg SC n=8 900 mg IV n=8 3000 mg IV n=8 Grade 1 5 (55.6) 5 (62.5) 7 (87.5) 5 (62.5) 3 (37.5) Grade 2 0 1 (12.5) 0 0 1 (12.5) Grade >3 0 0 0 0 0 Serious AE 0 0 0 0 0 AE leading to study discontinuation 0 0 0 0 0 Preliminary VIR-3434 Serum Concentration Profiles Following Single Subcutaneous or Intravenous Dose in Healthy Volunteers
VIR-3434 Mediated HBsAg Decreases from Baseline Most participants rapidly achieved ≥ 1 log10 IU/mL decline in HBsAg The largest reductions in HBsAg were in the 18 mg cohort, who also had higher baseline HBsAg levels Full analysis of VIR-3434 PK and HBsAg:VIR-3434 complex disposition is ongoing All participants on nucleos(t)ide reverse transcriptase inhibitors (NRTI) therapy HBsAg measured with Abbott ARCHITECT® © 2021 Vir Biotechnology, Inc. 1 2 Days HBsAg Change from Baseline, log10 IU/mL VIR-3434 6 mg or Placebo VIR-3434 18 mg or Placebo 1 Free VIR-3434 was undetectable in all available samples 2 Free VIR-3434 concentrations were lower than anticipated in all available samples
VIR-3434 Next Steps Higher single doses of VIR-3434 are being evaluated Patients with higher baseline HbsAg are being evaluated NRTI-naïve patients will be evaluated Multiple and higher doses of VIR-3434 will be evaluated in combination with VIR-2218 in the MARCH trial MARCH, Monoclonal Antibody siRNA Combination against Hepatitis B © 2021 Vir Biotechnology, Inc.
2H:2021 Anticipated Catalysts © 2021 Vir Biotechnology, Inc. COVID-19 HBV HIV Sotrovimab (mAb) BLA (Early Treatment, COMET-ICE, IV) File Sotrovimab (mAb) EMA rolling review (Early Treatment, COMET-ICE, IV) Complete Sotrovimab (mAb) Phase 2 (Early Treatment, COMET-PEAK, IM) Data VIR-7832 (mAb) Phase 1b (Early Treatment, AGILE, IV) Data VIR-2218 (siRNA) + VIR-3434 (mAb) Phase 2 Start VIR-2218 (siRNA) + GS-9688 + nivolumab Phase 2 Start VIR-3434 (mAb) Phase 1 additional clinical data Data VIR-2218 (siRNA) + PEG-IFN-⍺ Phase 2 additional clinical data Data VIR-1111 (T cell) Phase 1 Data