Q1 2024 Arbutus Biopharma Corp Earnings Call

May 2, 2024

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Operator: Good day, and thank you for standing by. Welcome to the Arbutus Biopharma 2024 First Quarter Financial Results and Corporate Update Conference Call. At this time, all participants are in a listen-only mode.

Speaker Change: Good day, and thank you for standing by welcome to the art Beautiful Biopharma 'twenty 'twenty four first quarter financial results and corporate update conference call.

Operator: After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1-1 on your telephone. You will then hear an automated message advising that your hand is raised.

Speaker Change: At this time all participants are in a listen only mode.

Speaker Change: After the speaker's presentation, there will be a question and answer session to.

Speaker Change: To ask a question during the session you will need to press star one on your telephone you will then hear an automated message advising enhances race.

Operator: To withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Lisa Caperelli, Vice President of Investor Relations. Please go ahead.

Speaker Change: To withdraw your question. Please press star one again please.

Speaker Change: Please be advised that today's conference being recorded I would now like to hand, the conference over to your first speaker today at least the copper Alley, Vice President of Investor Relations. Please go ahead.

Lisa M. Caperelli: Thank you, Andrea. Good morning, everyone, and thank you for joining Arbutus' first quarter 2024 financial results and corporate update call. Joining me today from the Arbutus executive team are Mike McElhaugh, interim president and chief executive officer, Dr. Karen Sims, chief medical officer, David Hastings, chief financial officer, and Dr. Mike Sofia, chief scientific officer. Mike McElhaugh will begin with a corporate update, followed by Karen, who will review our ongoing clinical program. Dave will then provide a review of the company's first quarter 2024 financial results.

Speaker Change: Thank you Andrea good morning, everyone and thank you for joining our beauty says first quarter 'twenty 'twenty four financial results and corporate update call.

Leslie Alley: Joining me today from the our beauty executive team are Mike Michael Hall, interim President and Chief Executive Officer, Dr. Karen Simms, Chief Medical Officer, David Hastings, Chief Financial Officer, and Dr. Mike Sofia, Chief Scientific Officer, Mike.

Speaker Change: Mike Michael Hall will begin with a corporate update followed by Karen who will review our ongoing clinical programs Dave.

David C. Hastings: Dave will then provide a review of the company's first quarter 2024 financial results. After our prepared remarks, we will open the call for Q&A.

Lisa M. Caperelli: After our prepared remarks, we will open the call for Q&A. Before we begin, I'd like to remind you that some of the statements made during the call today are forward-looking statements, which are subject to a number of risks and uncertainties that may cause our actual results to differ materially, including those described in our annual report on Form 10-K, our quarterly report on Form 10-Q, which will be filed today, and from time to time in our other documents filed with the FAC. With that, I'll turn the call over to Mike McElhaugh. Mike?

David C. Hastings: Before we begin I'd like to remind you that some of the statements made during the call. Today are forward looking statements, which are subject to a number of risks and uncertainties that may cause our actual results to differ materially including those described in our annual report on Form 10-K, our quarterly report on.

David C. Hastings: Form 10-Q, which will be filed today and from time to time in our other documents filed with the SEC.

Speaker Change: With that I'll turn the call over to Mike Michael Hall, Mike. Thanks, Lisa Good morning, everyone and thank you for joining us today.

Michael J. McElhaugh: Thanks, Lisa. Good morning, everyone, and thank you for joining us today. This morning, we issued two press releases, one announcing the end of year retirement of our co-founder and chief scientific officer, Dr. Mike Sofia, and one with our first quarter of 2024 financials and a corporate update. I want to pass the call to Mike Sofia to address his retirement.

Speaker Change: This morning, we issued two press releases one announcing the end of your retirement of our co founder and Chief Scientific Officer, Dr. Mike Sofia, and one with our first quarter of 2020 for financials and a corporate update.

Speaker Change: I want to pass the call to Mike Sofia to address this retirement.

Michael J. Sofia: Thanks, Mike, and good morning, everyone. Today, we announced my decision to retire as chief scientific officer at Arbutus, effective at the end of this year. I will continue in my full capacity as CSO until that time. Since co-founding Arbutus more than 10 years ago, the company has made incredible strides in its research and clinical trials. We have built an organization of dedicated individuals who are passionate about our mission to cure HPV. I continue to believe that Arbutus is on the correct path to developing a functional cure for the millions of patients living with HPV. My lifelong goal has been to discover medicines that improve patients' lives.

Michael J. Sofia: Thanks, Mike and good morning, everyone. Today, we announced my decision to retire as Chief Scientific officer at Arbutus effect at the end of this year.

Michael J. Sofia: I will continue in my full capacity, a CSO until that time.

Michael J. Sofia: Since co founding are viewed as more than 10 years ago. The company has made incredible strides in its research and clinical efforts. We have built an organization of dedicated individuals who are passionate about our mission to cure HBV.

Michael J. Sofia: I continue to believe that our beauty is on the correct path to developing a functional cure for the millions of patients living with HPV.

Michael J. Sofia: While iPhone goal has been to discover medicines that improve patients lives.

Michael J. Sofia: Over my 38-year career in pharma and biotech, one of my great successes was the discovery and development of sofosbuvir, the backbone of curative therapies for hepatitis C, which has already cured millions of patients globally. Learnings from the HCV story spurred me toward finding a cure for the more challenging problem, HBV. This led to the founding of Arbutus, where we have been able to build a world-class team uniquely positioned to potentially transform the HPV treatment landscape with drug candidates like Imdusiran and AB101.

Speaker Change: Over my 38 year career with pharma and biotech one of my great successes with the discovery and development of Sofosbuvir backbone of curative therapies for hepatitis C.

Speaker Change: As already cure millions of patients globally.

Speaker Change: Learnings from the HCV story spurred me towards finding a cure for the more challenging problem HBV.

Speaker Change: This led to the founding of argued us where we have been able to build a world class team uniquely positioned to potentially transform the HBV treatment landscape with drug candidates like him do surround and may be one on one.

Michael J. Sofia: Throughout my more than 10 years at Arbutus, I've enjoyed tackling the many challenges that drug discovery and development bring, collaborating with my colleagues, and mentoring many of the scientists. I am confident this passionate and dedicated team will continue to do great things. I have great pride in what we have been able to accomplish at Arbutus.

Speaker Change: Throughout more by more than 10 years at our Budapest I've enjoyed tackling the many challenges that drug discovery and development brings collaborating with my colleagues and mentoring many of the scientists here.

Speaker Change: I am confident this passionate and dedicated team will continue to do great things.

Speaker Change: A great pride in what we've been able to accomplish at our <unk>.

Michael J. McElhaugh: I look forward to following the future successes as the company advances its mission in finding a cure for HPV. Thank you, and back to Mike. Thanks, Mike. And thanks for everything you've done for Arbutus and our shareholders. I'm sure I speak for all employees when I say it's been an honor to work with you.

Speaker Change: We look forward to following the future successes as the company advances its mission and finding a cure for HBV.

Speaker Change: Thank you and back to Mike.

Speaker Change: Thanks, Mike and thanks for everything you've done for our view us and our shareholders I am sure I speak for all employees when I say, it's been an honor to work with you. We all wish you the best in your retirement.

Michael J. McElhaugh: We all wish you the best in your retirement. Now on to our Q1 Financial and Corporate Update press release that we issued today, announcing significant achievements made in advancing our pipeline in pursuit of developing a functional cure for patients with HPV and driving value for our company. We believe our two proprietary clinical assets in HPV, Induceran, our RNAi therapeutic, and AB101, our oral small molecule PD-L1 checkpoint inhibitor, have the potential to deliver on our three-pronged approach to functionally cure chronic HPV, which involves reducing surface antigen, suppressing HPV DNA, and boosting the immune system.

Speaker Change: Now onto our Q1 financial and corporate update press release that we issued today announcing significant achievements made in advancing our pipeline in pursuit of developing a functional cure for patients with HBV and driving value for our company.

Speaker Change: We believe our two proprietary clinical assets in HBV induced saran, our RNA therapeutic in <unk> hundred one our oral small molecule PD lone checkpoint inhibitor has the potential to deliver on our three pronged approach to functionally cure chronic HBV, which involves reducing surface antigen suppressing HBV.

Speaker Change: DNA and boosting the immune system.

Michael J. McElhaugh: While MDU-SIREN has shown activity in all three of these components in clinical trials conducted to date, we know a combination of agents is necessary to cure this challenging disease. I'll turn the call over to Karen shortly to walk through preliminary data from our Phase 1a, 1b clinical trial with AB101 and to provide an overview of our third Phase 2a clinical trial that is evaluating the combination of Induceran and Drevalumab, a PD-L1 monoclonal antibody that has begun screening patients.

Speaker Change: <unk> has shown activity in all three of these components in clinical trials conducted to date, we know a combination of agents are necessary to cure this challenging disease.

Speaker Change: I'll turn the call over to Karen shortly to walk through preliminary data from our phase <unk> clinical trial with <unk> 101, and to provide an overview of our third phase Iia clinical trial that is evaluating the combination of combination of inducer and enter value Mab, a PD lone monoclonal antibody, which has begun screening patients.

Michael J. McElhaugh: Currently, we have two phase 2a combination clinical trials, the AB729201 trial, which includes the addition of interferon, and the AB729202 trial, which includes the addition of Barenthus Biotherapeutics Immunotherapeutic VTP300. These trials are intended to provide data on the safety and efficacy of Induceran as a cornerstone therapy and to help us identify an optimal combination treatment that we can advance into a later This quarter, we will report end-of-treatment data from these two Phase 2a trials with Imdusiran, which could potentially include patients who achieve undetectable surface antigens.

Karen Sims: Currently we have two phase II combination clinical trials. The 79 201 trial, which includes the addition of interferon and the 79 202 trial, which includes the addition of Brent This biotherapeutics immuno therapeutic ETP 300.

Karen: These trials are intended to provide data on the safety and efficacy of inducer and is a cornerstone therapy and to help us identify an optimal combination treatment that we can advance into later stage clinical trial.

Karen Sims: This quarter, we will report end of treatment data from these two phase III trials with <unk>, which could potentially include patients who achieved undetectable surface antigen.

Michael J. McElhaugh: As we've previously stated, achieving undetectable surface antigen in either of these two Phase IIa clinical trials would be an important validation of Imdusiran's role as a cornerstone in potentially achieving a functional cure for patients with chronic HPV.

Karen Sims: As we've previously stated achieving undetectable surface antigen in either of these two phase III clinical trials would be an important validation of <unk> role as a cornerstone in potentially achieving a functional cure for patients with chronic HBV.

Michael J. McElhaugh: We are happy to report that two abstracts, including data from these Phase IIa clinical trials, were accepted for presentation at the ESL Congress, which takes place in early June in Milan, Italy. We will provide more details on those abstracts at a later date. With that, I'll turn the call over to Karen to provide an overview of the AB-729-203 clinical trial and discuss the AB-101 Phase I preliminary data. I'll come back at the end of the team's prepared remarks to provide an update on our LNP litigation before we move into Q&A. Karen?

Karen Sims: We are happy to report that two abstracts, including data from these phase III clinical trials were accepted for presentation at the Easel Congress, which takes place in early June in Milan, Italy.

Karen Sims: We'll provide more details on those abstracts at a later date.

Karen Sims: With that I'll turn the call over to Karen to provide an overview of the ABP 790, <unk> hundred three clinical trial and to discuss the <unk> 101 phase one preliminary data I'll come back at the end of the team's prepared remarks to provide an update on our LNP litigation before we move into Q&A Karen.

Karen Sims: Thanks, Mike. And good morning, everyone. As Mike mentioned, our approach to developing a functional cure for patients with chronic hepatitis B involves reducing surface antigen, suppressing HBV DNA, and boosting the immune system. And our clinical trials conducted to date have been shown to reduce HBV DNA in untreated patients and reduce surface antigen when given both with and without ongoing standard of care and nuke therapy. In addition, evidence of HDV-specific T-cell reawakening has been observed in some patients undergoing treatment with induced NIRAN.

Karen: Thanks, Mike and good morning, everyone as Mike mentioned, our approach to developing a functional cure for patients with chronic hepatitis b involves reducing surface antigen suppressing HBV DNA and boosting the immune system and our clinical trials conducted to date in <unk> has been shown to reduce HBV DNA in untreated patients and reduce surface.

Karen: And when given both with and without ongoing standard of care in Nuc therapy and.

Karen: In addition evidence of HBV specific T cell reawakening has been observed in some patients undergoing treatment with <unk>.

Karen Sims: To further boost the immune system, we designed our Phase IIa trials to evaluate induced RAN in combination with one of three immunomodulatory approaches, interferon, a therapeutic vaccine, or a checkpoint inhibitor targeting the PD-1, PD-L1 axis. Our two ongoing phase 2A clinical trials, AB729-201 and AB729-202, are evaluating Induceran in combination with interferon and in combination with As Mike said, both of these phase 2a trials are on track to report end of treatment data at the easel congress in June.

Karen Sims: To further boost the immune system, we designed our phase Iia trial to evaluate <unk> in combination with one of three immuno modulator sorry approaches.

Karen Sims: Interferon, a therapeutic vaccine or checkpoint inhibitor targeting the PD, one PD lone access.

Karen Sims: Note that we have amended the AB-729-202 trial to evaluate the addition of the PD-1 checkpoint inhibitor antibody nivolumab to the induced saran and DTP-300 combination. We expect preliminary end-of-treatment data from that cohort in the second half of this year.

Karen Sims: Our two ongoing phase Iia clinical trial, 80% 79, 201, and 80 790 <unk> are evaluating <unk> in combination with interferon and in combination with a therapeutic vaccine respectively.

Karen Sims: As Mike said both of these phase III trials are on track to report end of treatment data at the <unk> Congress in June.

Karen Sims: We also amended the 80% 79, two trial to evaluate the addition of the PD one checkpoint inhibitor antibody developed map to the induced <unk> and BCP 300 combination.

Karen Sims: We expect preliminary ended treatment data from that cohort in the second half of this year.

Karen Sims: Today, we announce that we have initiated patient screening in our third phase 2A clinical trial, AB729203, which is evaluating inducerin in combination with Dervalumab, an antipedial monoclonal antibody. While all of these Phase IIa trials are geared towards finding the right immune modulator to combine with induced NIRAN, the AB729203 trial with Dervalumab is specifically intended to evaluate how we can use checkpoint inhibition in combination with induced NIRAN to boost HDV-specific immune responses.

Karen Sims: Today, we announced that we have initiated patient screening in our third phase Iia clinical trial, <unk>, three which is evaluating <unk> in combination with their value Nab and anti PDL one monoclonal antibody.

Karen Sims: While all of these phase III trials are geared towards finding the right immune modulator to combined with Easter in the AB 790, <unk> III trial with their value Mab is specifically intended to evaluate how we can use checkpoint inhibition in combination with MDU saran induced HBV specific immune responses.

Karen Sims: This trial will inform upcoming combination with our proprietary oral small molecule PD Lone checkpoint inhibitor gave you wanted one.

Karen Sims: This trial will inform upcoming combinations with our proprietary oral small molecule PD-L1 checkpoint inhibitor, AB101. With that in mind, I'd like to provide more information regarding the AB729-203 trial design. AB 179203 is an open-label, multi-sensory, phase 2a clinical trial evaluating the safety, tolerability, antiviral, and HPV-specific immunologic activity of MDUCRAN and ongoing Duke therapy in combination with Dervalumab, an approved anti-PD-L1 monoclonal antibody in patients with chronic hepatitis B. We intend to enroll 30 virologically suppressed patients into three separate

Karen Sims: With that backdrop I'd like to provide more information regarding the <unk> 79 to <unk> III trial design.

Karen Sims: 87% to 9203 is an open label Multicenter phase Iia clinical trial evaluating the safety Tolerability antiviral and HD. These specific immunologic activity of <unk> and ongoing <unk> therapy in combination with your value add and approved anti PDL, one monoclonal antibody in patients.

Karen Sims: With chronic hepatitis b.

Karen Sims: We intend to enroll 30 virological suppressed patients into three separate cohort.

Karen Sims: All patients will receive 60 milligrams of Imduceran every 8 weeks with their ongoing Duke therapy for 48 weeks and will receive 2 doses of Dervalumab at pre-specified times during the Imduceran treatment period that will differ by cohort.

Karen Sims: All patients will receive 60 milligrams of <unk> every eight weeks with their ongoing nuc therapy for 48 weeks.

Karen Sims: Will receive two doses of their value map at pre specified time during the end user and treatment period that will differ by cohort.

Karen Sims: After completion of treatment, all patients will be assessed for eligibility to discontinue NUCC therapy and will be followed for an additional 24 to 48 weeks. The endpoints for this clinical trial include safety and changes in surface antigen from baseline during the treatment and follow-up period. This trial allows us to explore the optimal timing of checkpoint inhibitor dosing in the context of surface antigen reduction during ongoing induced trans treatment. Now, moving on to our proprietary oral small molecule checkpoint inhibitor, AB101, that is differentiated from monoclonal antibodies, such as drivalumab and nivolumab, in the following ways based on our preclinical testing.

Karen Sims: After completion of treatment all patients will be assessed for eligibility to discontinue nuc therapy and will be followed for an additional 24 to 48 weeks.

Karen Sims: The endpoints for this clinical trial include safety and changes in surface antigen from baseline during the treatment and follow up period.

Karen Sims: This trial allows us to explore the optimal timing of checkpoint inhibitor dosing in the context of surface antigen reduction during ongoing <unk> treatment.

Karen Sims: First, AB101 is liver-centric, meaning it preferentially reaches the liver and has a high liver-to-plasma ratio, thus minimizing systemic exposure and reducing the chance of immune-related adverse events seen with monoclonal antibodies. Second, AB101 has typical small molecule pharmacokinetics and therefore a much shorter duration of effect than long-acting antibodies, thus allowing for the potential to modify the dose or dosing interval to maximize effect or to stop dosing to quickly mitigate any safety concern. Third, AB101 acts through a novel mechanism of action, differentiated from antibodies. It binds to PD-L1 on the surface of cells, causing dimerization and internalization of the PD-L1 protein, followed by degradation within hours.

Karen Sims: Now moving onto our proprietary oral small molecule checkpoint inhibitor AB 101 that is differentiated from monoclonal antibodies such as <unk> in the following ways based on our preclinical testing.

Karen Sims: First one on one as liver centric, meaning it preferentially traffics to the liver and has a high liver to plasma ratio, thus minimizing systemic exposure and reducing the chance of immune related adverse events seen with monoclonal antibodies.

Karen Sims: Second <unk> hundred one has typical small molecule pharmacokinetics and therefore, a much shorter duration of effect and long acting antibodies, thus, allowing for the potential to modify the dose or dosing interval to maximize the effect or to stop dosing to quickly mitigate any safety concern.

Karen Sims: Third 80, 101 acts through a novel mechanism of action differentiated from antibiotics.

Karen Sims: To PDL, one on the surface of cells, causing dimerization and internalization of the PD lone protein followed by degradation within hours.

Karen Sims: Washing out of the drug results in full reconstitution of PD lone on the cell surface and restoration of PDL one function within days.

Karen Sims: <unk> antibody therapy for the duration of receptor occupancy and PD effect is maintained for weeks with no ways to reverse it.

Karen Sims: Squashing out the drug results in full reconstitution of PD-L1 on the cell surface and restoration of PD-L1 function within days, unlike antibody therapy, where the duration of receptor occupancy and the PD effect is maintained for weeks with no way to reverse it. It is for these reasons that we are excited about the potential of AB101 in HBV and are advancing our AB101 clinical program, which is currently evaluating AB101 in a double-blind, randomized, placebo-controlled, phase 1A, 1B clinical trial known as AB101-001.

Karen Sims: It is for these reasons that we're excited about the potential of <unk> 101 in HBV and advancing our <unk> hundred one clinical program, which is currently evaluating <unk> 101 in a double blind randomized placebo controlled phase <unk> clinical trial known as <unk> 101 001.

Karen Sims: This trial is designed to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of AB101. The trial consists of three parts, starting with single and multiple ascending doses in healthy subjects and culminating with multiple doses in patients with chronic HPV. In Part 1, which is the single ascending dose portion of the trial, we have enrolled four sequential cohorts of eight healthy subjects each to date. Within each cohort, six subjects received AB101, and two subjects received placebo.

Karen Sims: This trial is designed to investigate the safety Tolerability pharmacokinetics and pharmacodynamics of <unk> 101.

Karen Sims: After review of safety, PK, and PD data, AB101 dose levels were increased in each subsequent cohort up to 25 milligrams. The data from Part 1 show that AB101 is generally well-tolerated with evidence of dose-dependent receptor occupancy. In the 25-milligram cohort, five of the six subjects had test samples that were valuable for receptor occupancy, and all five of these subjects showed evidence of PD-L1 receptor occupancy between 50 and 100 percent, indicating that AB101 is interacting with its intended target. One subject in this cohort was excluded from the PD evaluation as their samples could not be analyzed.

Karen Sims: The trial consists of three parts, starting with single and multiple ascending doses in healthy subjects and culminating with multiple doses in patients with chronic HBV.

Karen Sims: In part one which is the single ascending dose portion of the trial, we have enrolled four sequential cohorts of eight healthy subjects each to date within a cohort six subjects received <unk> hundred one and two subjects received placebo and after review of safety PK and PD data <unk> dose levels were increased in each subsequent.

Karen Sims: Cohort up to 25 milligram.

Karen Sims: <unk> test samples that were evaluable for receptor occupancy and all five of these subjects showed evidence of PD lone receptor occupancy between 50, and 100%, indicating the AED 101 is interacting with its intended target.

Karen Sims: One subject in this cohort was excluded from the PD evaluation at their samples cannot be analyzed.

David C. Hastings: We are now in Part 2 of this trial, where cohorts of healthy subjects are receiving multiple ascending doses of AB101. Our goal is to move as quickly as possible into Part 3, which will enroll patients with chronic hepatitis B. We anticipate announcing preliminary data from Part 2, the multiple ascending dose portion of this trial in healthy subjects in the second half of this year. We believe that the immune checkpoint pathway plays an important role in HBV-specific immune tolerance and in T-cell activation, and the addition of a checkpoint inhibitor in combination with induced RAN could potentially further enhance HBV-specific immune responses. With that, I'll turn the call over to Dave Hastings for a brief financial update. Dave?

Karen Sims: We are now in part two of this trial were cohorts of healthy subjects are receiving multiple ascending doses of <unk> hundred one.

Karen Sims: Our goal is to move as quickly as possible into part three which will enroll patients with chronic hepatitis b.

Karen Sims: We anticipate announcing preliminary data from part two the multiple ascending dose portion of this trial in healthy subjects in the second half of this year.

Karen Sims: We believe that the immune checkpoint pathway plays an important role HBV specific immune tolerance and in T cell activation and the addition of a checkpoint inhibitor in combination with <unk> could potentially further enhanced HBV specific immune responses.

Karen Sims: With that I'll turn the call over to Dave Hastings for a brief financial update.

David C. Hastings: Thanks, Karen, and good morning, everybody. We ended the first quarter of 2024 with approximately $138 million of cash, cash equivalents, and investments, compared to approximately $132 million as of December 31, 2023. During the quarter ended March 31st, 2024, we received $21.8 million of net proceeds from the issuance of common shares under Arbutus' At-The-Market Offering Program. These cash inflows were offset by $19.3 million of cash used in operations.

David C. Hastings: Thanks, Karen and good morning, everybody.

David C. Hastings: We still expect our 2024 net cash burn to range from between $63 to $67 million, excluding any proceeds from our ATM program. In April 2024, we received an additional $22.4 million in net proceeds from sales of our ATMs. And now importantly, we believe our cash runway is sufficient to fund our operations through the second quarter of 2026. So, in closing, we have a strong financial position to advance our mission of developing our HPV assets to provide a functional cure for chronic HPV. With that, I'll turn the call back to Mike. Thanks, Dave.

David C. Hastings: We ended the first quarter of 2024 with approximately $138 million of cash cash equivalents and investments <unk>.

David C. Hastings: <unk> to approximately $132 million as of December 31, 2023.

David C. Hastings: During the quarter ended March 31, 2024, we received $21 8 million of net proceeds from the issuance of common shares.

David C. Hastings: Under our <unk> at the market offering program.

David C. Hastings: These cash inflows were offset by $19 3 million of cash used in operations.

David C. Hastings: We still expect our 2024 net cash burn to range from between <unk> $63 million to $67 million, excluding any proceeds from our ATM program.

David C. Hastings: In April 2024, we received an additional $22 4 million in net proceeds from sales of our ATM.

David C. Hastings: And now importantly, we believe our cash runway is sufficient to fund our operations through the second quarter of 2026.

David C. Hastings: So in closing we have a strong financial position to advance our mission of developing our HBV assets to provide a functional cure for chronic HBV.

David C. Hastings: With that I'll turn the call back to Mike.

Michael J. McElhaugh: With today's update, we have achieved most of our first half of 2024 key milestones, including reporting preliminary data from the AB 101-001 Phase Ia-Ib clinical trial and initiating the Phase IIa clinical trial with MDU-SIREN and your ValueMap. We look forward to reporting data from the AB-729-201 and AB-729-202 Phase 2A clinical trials at ESL in June. In the second half of this year, we anticipate preliminary end-of-treatment data from the Novolumab arm of the 202 trial and preliminary multiple ascending dose data from healthy subjects in the AB 101-001 trial.

Michael J. Sofia: Thanks, Dave.

Michael J. Sofia: Today's update we have achieved most of our first half 2024 key milestones, including reporting preliminary data from the <unk> 101, 001 phase <unk> clinical trial and initiating the phase Iia clinical trial with inducer and Andrew value map.

Michael J. Sofia: We look forward to reporting the data from the <unk> 79, 201, and 202 phase Iia clinical trials at diesel in June.

Michael J. Sofia: In the second half of this year, we anticipate preliminary end of treatment data from the volume at arm of the 202 trial and preliminary multiple ascending dose data from the healthy subjects and the AED 101 001 trial.

Michael J. McElhaugh: 2024 is off to a strong start, and it wouldn't be possible without the dedication of my Arbutus colleagues. I would like to take this opportunity to thank all of them for their hard work to advance our pipeline. Before turning the call over to Q&A, I'd like to provide a brief update on the ongoing patent infringement lawsuit, specifically the lawsuit against Moderna. As you may recall, on February 8th of this year, there was a claim construction hearing, also commonly referred to as the Markman hearing, where the court heard each party's interpretation of the construction of claims in the disputed patent. The court issued its order on April 3rd, in which it agreed with our position on most of the disputed claim terms.

Michael J. Sofia: 2024 is off to a strong start and it wouldn't be possible without the dedication of my <unk> colleagues I would like to take this opportunity to thank all of them for their hard work to advance our pipeline.

Michael J. McElhaugh: This is another important step in the ongoing litigation process and provides clarity on the interpretation of key terms and the scope of the claim. I refer you to the press release that we issued on April 4th, which is available on our website, and summarizes the claims related to the three patents that were presented at the Markman hearing and the court's position on each claim. While this is important for us, we cannot further comment or elaborate on what is in the press release, but we suggest you review the judge's opinion, which is also available on our website. In his opinion, the judge provides an overview of the disputed aspects of each claim and each party's position, as well as the evidence that was used to inform his decision-making process.

Michael J. Sofia: Before turning the call over to Q&A I'd like to provide a brief update on the ongoing patent infringement lawsuit specifically the lawsuit against Madonna.

Michael J. Sofia: As you May recall on February eight of this year. There was a claim construction hearing also commonly referred to as the Markman hearing where the court heard each party's interpretation of the construction of claims and disputed patents.

Michael J. Sofia: The court issued its order on April <unk>, and which had agreed with our position on most of the disputed claim terms. This is another important step in the ongoing litigation process and provides clarity on the interpretation of key terms and the scope of the claims.

Michael J. Sofia: I refer you to the press release that we issued on April 4th which is available on our website and summarizes the claims related to the three patents that were presented at the markman hearing an important position on each claim.

Michael J. Sofia: While this is important for us we cannot further comment or elaborate on what is in the press release, but we suggest you review the judge's opinion, which is also available on our website in his opinion. The judge provides an overview of the disputed aspects of each clean and each party's position as well as the evidence that was used to inform us.

Michael J. Sofia: Cision, making process.

Michael J. Sofia: The litigation process continues to move forward fact discoveries ongoing and next steps include expert reports and depositions.

Michael J. Sofia: The Court has set April 21, 2025 as the trial date for this case that date is subject to change.

Michael J. McElhaugh: The Pfizer BioNTech lawsuit is ongoing, and a date for the claim construction hearing for that case has not yet been set. We will continue to protect and defend our intellectual property, including our LNP delivery technology. All of our scientists take great pride in the intellectual property they develop, which takes great effort, time, resources, and expense.

Michael J. Sofia: The Pfizer <unk> Tech lawsuit is ongoing and a date for the claim construction hearing for that case has not yet been set.

Michael J. Sofia: We will continue to protect and defend our intellectual property, including our LNP delivery technology all of our scientists take great Pride in Illinois intellectual property, they develop which takes great effort time resources and expense <unk>.

Operator: Operator, we're now ready to open the call for Q&A. Thank you. At this time, we will conduct the question and answer session. As a reminder, to ask a question, you will need to press star 1 1 on your telephone and wait for your name to be announced.

Speaker Change: Operator, we're now ready to open the call for Q&A.

Speaker Change: Thank you at this time, we will conduct a question and answer session. As a reminder to ask a question you will need to press star one on your telephone and wait for your name to be announced to withdraw. Your question. Please press star one again, please standby, while we compile the Q&A roster.

Operator: To withdraw your question, please press star 11 again. Please stand by while we compile the Q&A roster. Our first question comes from Dennis Ding with Jeffries. Please go ahead. Hi, good morning.

Yuchen Ding: Thanks for taking our questions. Two, if I may, on the pipeline, you guys have a few phase two trials with, you know, a lot of different combinations going on. But how about when do you think we can get any functional cure signals? And is that a 2025-type event, or can we get some data later this year? And then number two, you know, you know, I appreciate you starting a new phase two with DERVA, but I'm just curious, how much more data do you think you'll need from your hepatitis B trials before you can start phase three? I'm just wondering what...

Speaker Change: Our first question comes from Dennis <unk> with Jefferies. Please go ahead.

Michael J. McElhaugh: The Gating factor is there, waiting for AB 101 to show some combo data or the data from the new DERBA study, which is essentially one year treatment and one year follow-up. So I'm just wondering what the gating factor is there. Thank you. Good morning, Dennis. Thanks. Thanks for the question. So Karen, do you want to handle Dennis's first question on Functional Cure? Excuse me, yes, Functional Cure.

Dennis: Hi, good morning, Thanks for.

Dennis: Taking my questions two if I may on the pipeline.

Dennis: You guys have a few phase two trials with a lot of different combinations going on but.

Dennis: Anything we can get any functional cures signals and is that a 2025 type et cetera.

Dennis: Or can we get some data later this year.

Dennis: And then number two.

Dennis: I appreciate you're starting a new phase two with <unk>.

Dennis: I'm just curious how much more data do you think.

Dennis: Need from hepatitis B trials before you can start a phase III I'm just wondering what is the gating factor here is the waiting for maybe 101 to show some combo data or the data from the New service study, which is essentially one year treatment and one year follow up I was just wondering what the gating factors there. Thank you.

Speaker Change: Good morning, guys. Thanks for thanks for the question. So Karen do you want to handle Dennis as first question on.

Speaker Change: Functional cure excuse me, yes functional cures.

Karen Sims: So, you know, Dennis, as you know, as you just stated, these trials do take some time, including the treatment period and the extended follow-up period. And as you know, functional cure signals can't be assessed until subjects are at least six months off of all treatment. So that is ongoing in both of our phase two studies at the moment, both the 201 interferon study and the 202 study in combination with BTP 300.

Karen: Sure absolutely so Dennis as you know these as you just stated these trials do take some time, including the treatment period and the extended follow up period and as you know a functional store signals can't be assess until subjects or at least six months off of all statements. So that is ongoing in both of our phase III studies at the moment, both the tier one interferon study AMETEK.

Speaker Change: <unk> study in combination with <unk> for instance is edp 300 or so.

Karen Sims: So, you know, as the data comes in and as we are able to compile that data into a meaningful data release with a sufficient number of subjects, we'll certainly share that data when we can. So I can't give any additional guidance just to say that the trials are ongoing, and we'll present the data as it becomes available. Okay, and then on to the second question, which was regarding the value map and when we might be able to start a follow-on trial. I think the answer to that question, Dennis, is it's going to depend on what we see from our existing ongoing studies, right?

As the data comes in and as we are able to compile that data into a meaningful data released with sufficient number of subjects, we'll certainly share that data when we can so I can't give any additional guidance just to say that the trials are ongoing and we will.

Karen Sims: We'll present the data as it becomes available.

Speaker Change: Okay.

Karen Sims: And then on to the second question was in regards to <unk> and when we might be able to start a follow on trial I think the answer to that question. Dennis says, it's going to depend on what we see from our existing ongoing studies alright. So yes, we're starting a new trial and yes, we think that will be valuable in helping to inform how we think about the addition of <unk> 101 to inducer.

Michael J. McElhaugh: So, yes, we're starting a new trial, and, yes, we think that will be valuable in helping to inform how we think about the addition of AB101 to Induciran, but, as Karen just mentioned, we have some trials ongoing, which could, of course, produce interesting data, which could then lead to follow-on studies. So, I don't think that it's a situation where we need to wait until we have the full picture from all of these ongoing trials before we decide what we're going to do to move forward.

Michael J. McElhaugh: But as Karen just mentioned, we have some trials ongoing which could of course produce interesting data, which could then be two follow on studies. So.

Michael J. McElhaugh: Don't think that its a situation where we need to wait until we have the full picture from all of these trials ongoing before we decide what we're going to do to move forward. As you know the goal here is functional cure if we can deliver some functional cures in any of the ongoing studies, we will obviously be moving as quickly as possible into follow on studies.

Michael J. McElhaugh: As you know, the goal here is a functional cure. If we can deliver some functional cures in any of the ongoing studies, we will obviously be moving that as quickly as possible into follow-on studies. All right, thank you.

Speaker Change: Got it thank you.

Speaker Change: One moment for our next question.

Michael J. McElhaugh: Okay.

Operator: Thank you. Thank you. Our next question comes from Ed Arce with H.C. Wainwright. Please go ahead. Good morning, everyone.

Michael J. McElhaugh: Our next question comes from Ed Arce with H.

Ed Arce: H C. Wainwright. Please go ahead.

Ed Arce: This is Thomas Yip asking a couple of questions for Ed. Thank you for taking the questions. So first, perhaps, following up with the previous question, just moving forward and doing CIRAN. What would the next phase, you know, phase 2B or phase 3 study, would that be expected to be that way in group serine, that amount of ferritin, or in combination, or perhaps both? So, Thomas, good morning. Thank you. This is Mike.

Operator: Good morning, everyone. This is Thomas Yip asking a couple of questions for us. Thank you for taking the questions.

Mike: So first off perhaps.

Mike: Following up with.

Mike: With a previous question.

Mike: Just looking for.

Ed Arce: <unk>.

Mike: With the mix.

Mike: PCB or phase III study with <unk>.

Mike: That would be expected to be that way.

Mike: And as a monotherapy.

Mike: And the combination or perhaps both.

Michael J. McElhaugh: I think we've always said that we're going to have to think about combination therapy when it comes to curing HPV. We have to hit those three pillars that we talk about frequently. So I think as we think about what a next study might look like, it's definitely going to be a combination study. Okay. Perhaps one question for Dr. Sims.

Ed Arce: So Thomas good morning. Thank you this is Mike.

Michael J. McElhaugh: We've always said that.

Michael J. McElhaugh: That we're going to have to think about combination therapy. When it comes to curing HBV, we have to hit those three pillars that we talk about frequently.

Karen Sims: So I think as we think about what the next study might look like it's definitely going to be a combination study.

Karen Sims: For the new phase 2a study with the viral map, can you discuss the rationale behind different dosing intervals for the viral map and what is the significance of analyzing these different dosing intervals? Yeah, thanks for the question, Thomas. So, the idea here is evaluating the extent of checkpoint inhibition that's necessary to try to induce that HPV-specific immunity. And as I'm sure you're aware, the use of checkpoint inhibitor therapy in oncology is a much different dosing regimen and much different dosing level. So, it's very high doses over repeated cycles for weeks to months, and with that comes a safety profile that may not be optimal in patients with chronic hepatitis B.

Sims: Understood, perhaps one question for Dr. <unk>.

Karen Sims: <unk>.

Karen Sims: With a new phase III study with the road map.

Karen Sims: Can you just can you discuss the rationale behind.

Speaker Change: So as the interval for development.

Speaker Change: And what was the significance.

Karen Sims: Q2 annualized.

Karen Sims: Dosing intervals.

Karen Sims: Yeah. Thanks for the question so the IDE.

Karen Sims: Here is evaluating the the extent of checkpoint inhibition, that's necessary to try to induce that HBV specific immunity. So as I'm sure. You are aware the use of checkpoint inhibitor therapy and oncology is a much different dosing regimen and much different dosing levels. So it's very high doses.

Karen Sims: Were repeated cycles for six months and with that comes a safety profile that may not be optimal in patients with chronic hepatitis b. So what we're looking to do is strike the appropriate balance between having a regimen that safe and well tolerated for these patients with chronic hepatitis b as well as trying to understand exactly when we need to <unk>.

Karen Sims: So, what we're looking to do is strike the appropriate balance between having a regimen that's safe and well-tolerated for these patients with chronic hepatitis B, as well as trying to understand exactly when we need to intervene on the checkpoint inhibitor axis in the context of the surface antigen reduction that we see with induced ARAN. So, that's the idea behind the trial, is it best to inhibit the checkpoint axis during the acute decline of surface antigen, or is it best to inhibit it after surface antigen has reached a nadir, somewhere in between, and, you know, doing that at multiple time points. So that's the idea behind the trial is really to strike that balance between optimal immunomodulatory effects and maintaining a very good safety profile for this patient population. understood.

Karen Sims: On the checkpoint inhibitor axis in the context of the surface antigen reduction that we see with a noose around so that's the idea behind the trial is it best to <unk>.

Karen Sims: Inhibit the checkpoint axis during the acute decline in surface antigen is it best to inhibit after surface antigen has reached the nadir somewhere in between and doing that at multiple time points. So that's the idea behind the trial is really to strike that balance between optimal immuno module Tory effects, but maintaining a very good safety profile for this patient.

Karen Sims: Population.

Karen Sims: And perhaps one last question for AB 101. After completing the multi-ascending dose phase of the ongoing phase one study, what's the next step for the program? Would that be looking at a combination study in HPV, or are there other areas that AB 101 can have potential in? Sure, yeah, thanks for the question.

Karen Sims: Understood.

Speaker Change: Perhaps one last question for EB 101.

Speaker Change: After completing the multi ascending dose phase.

Speaker Change: Ongoing phase one study.

Speaker Change: The next step for the program.

Karen Sims: B.

Karen Sims: <unk>.

Speaker Change: Looking at the.

Speaker Change: A combination study in HBV or are there other areas.

Speaker Change: Areas that maybe 101 kind of potential.

Karen Sims: Again, just to clarify, so the current study is a three-part study, so single doses in healthy subjects, then multiple doses in healthy subjects, and then we move seamlessly into multiple doses in patients with chronic hepatitis B in combination with new therapies. So we need to complete those different portions of the trial to understand the safety profile, the pharmacokinetic profile, and the PD profile of AB101 to be able to enter that next phase of studies.

Speaker Change: Sure Yes. Thanks for the question again, just to clarify so the current study is a three part study so single doses in healthy subjects than multiple doses in healthy subjects and then we move seamlessly into multiple doses in patients with chronic hepatitis b in combination with nuc therapy, So we need to complete those.

Karen Sims: Portions of the trial to understand the safety profile of the pharmacokinetic profile of the PD profile of <unk> 101 to be able to answer that next phase of studies, but certainly you can imagine after completion of the phase. One study. The next goal would be to put it in combination with <unk> in a phase II study as quickly as possible.

Karen Sims: But certainly, you can imagine after completion of the phase one study, the next goal would be to put it in combination with induced saran in a phase two study as quickly as possible. Understood. Thank you again for taking all questions and looking forward to the ESO daily readout. You're welcome, Thomas.

Speaker Change: Understood. Thank you.

Speaker Change: Again for taking all the questions and looking forward to the easel data readouts.

Speaker Change: Youre welcome Thomas Thank you.

Operator: Thank you. Thank you. Our next question comes from Brian Skorney with Baird. Please go ahead. Hey guys, thanks for taking our question and congratulations and best wishes to Mike. This is Charlie on behalf of Brian. So just a couple from us.

Speaker Change: Thank you one moment for our next question.

Charlie: Our next question comes from Brian <unk> with Baird. Please go ahead.

Charlie: Hey, guys. Thanks for taking our question.

Operator: Congratulations and best wishes to Mike This is Charlie on for Brian.

Speaker Change: So just a couple from US just wondering when youre thinking about dosing with <unk> 101.

Brian Peter Skorney: Just wondering when you're thinking about dosing with AB-101, it sounds like so far you've seen good safety data, but I just would be curious if you're kind of thinking of 25 migs as a cap in the MAD as well. And then, you know, are you, when you're thinking about this, the Dervalumab trial, have you seen anything from the Nevo combination so far that might be playing into your thinking on different timings? And then just one more on an early stage asset in the space.

Brian Peter Skorney: It sounds like so far <unk> seen good safety data, but just would be curious if youre kind of thinking of 25 mix as a cap in the mad as well.

Brian Peter Skorney:

Brian Peter Skorney: And then.

Brian Peter Skorney: Are you when youre thinking about this.

Brian Peter Skorney: The <unk> trial have you seen anything from the <unk> combination so far that might be.

Brian Peter Skorney: Going into your thinking on different timings and then just one more on an early stage asset in this space what are your thoughts on <unk> agonism. If you have any at this point. Thank you so much.

Operator: What are your thoughts on ALPK1 agonism, if you have any at this point? Thank you so much. All right. So, Charlie, good morning.

Michael J. McElhaugh: Thanks for the question. So, Karen, why don't you handle the question with regard to AB101 and the NEBO-related question about drivalumab? Yeah, sure. Absolutely.

Speaker Change: Alright, so Charlie good morning, Thanks for the questions. So Karen.

Karen Sims: Why don't you handle the question with regards to <unk> hundred one in the.

Karen Sims: Nouveau lead to devalue that question, yes.

Karen Sims: So, the data we're sharing thus far is just, you know, the extent of dosing we've completed with AB101. So, it's too early to comment on the dosing that we'll be using in the next portions of the trial. We do have flexibility in the trial in all the different arms to either increase dose, decrease dose, or make changes to dosing regimens. So, you know, 25mg, as reported today, is the highest dose we've tested with an excellent safety profile and good pharmacodynamic profile. So, you know, we'll be evaluating different dosing levels as we move on through the trial. So, 25 isn't necessarily a cap.

Karen Sims: Yes, sure absolutely so.

Karen Sims: The data we're sharing thus far is just the extensive dosing we've completed with <unk> 101. So it's too early to comment on the dosing that we'll be using in the next portions of the trial, we do have flexibility in the trial and all the different arms to either increase dose decreased Jos made changes to adjusting regimen. So 25 years as.

Karen Sims: Today. It is the highest as we tested with an excellent safety profile and good pharmacodynamic profile. So we'll be evaluating different dosing levels as we move on through the trial. So 25 isn't necessarily a cap. It's just the data we have available to share with you today.

Karen Sims: It's just, you know, the data we have available to share with you today. So, and in terms of the nivolumab data coming out of the 202 study, obviously, I can't comment on that. You know, we provided guidance that we'll be sharing the preliminary end-of-treatment data at the end of the year, the second half of this year. So, you know, that data I can't comment on, but certainly, you know, we look at all of our trials holistically and, you know, certainly, you know, would, as Mike said earlier, move forward or, you know, adapt as we see the data emerging from our trials. But yeah, to date, I can't comment on anything regarding the nivolumab arm in the 202 study. And then, Mike, do you want to handle the last question?

Speaker Change: And in terms of the <unk> date.

Mike: <unk> data coming out of the 202 study, obviously I can't comment on that when we provided guidance that we'll be sharing the preliminary end of treatment data at the ended the year in the second half of this year. So that data I can't comment on but certainly we look at all of our child Holistically and certainly.

Karen Sims: What as Mike said earlier move forward or adapt as we see the data emerging with our trials, but yet to date I can't comment on anything regarding the <unk> study.

Michael J. McElhaugh: Yeah, on the ALPK1 question, yeah, we're aware that an abstract just came out at EASL on that. Frankly, it just came out, so we are, you know, we'd be interested in looking at the abstract more clearly, more fully, and obviously seeing the presentation at EASL to get a full understanding of the target. Gotcha. Great. Thanks so much for the questions, guys. Thanks, Charlie.

Karen Sims: And then Mike do you want to handle the last question.

Michael J. McElhaugh: EMEA LPTA one cross.

Michael J. McElhaugh: Yes, we are aware of the infrastructures came out diesel.

Michael J. McElhaugh: <unk>.

Michael J. McElhaugh: No.

Michael J. McElhaugh: Frankly, it just came out so we are interested.

Michael J. McElhaugh: Interested in looking at the abstract more more fully and obviously seeing the presentation of diesel.

Michael J. McElhaugh: Get a full understanding of the target.

Michael J. McElhaugh: Got you great. Thanks, so much for the questions guys.

Speaker Change: Thanks, Charlie Charlie.

Speaker Change: One moment for our next question.

Operator: One moment for our next question. Our next question comes from Rory Buchanan with Citizens JMP. Please go ahead.

Michael J. McElhaugh: Our next question comes from Brett Buchanan with citizens JMP. Please go ahead.

Douglas Royal Buchanan: Hey, thanks for taking the questions. Obviously, congrats to Mike Sofia on the planned retirement, and it definitely made deep insights and observations on the cause. You have eight months to get to a functional cure, um, Yeah, just a few questions. So, I guess on the 203 trial, I think there's a typo on the slide that says Q48 weeks, and I think Karen said every eight weeks, which makes a lot more sense. So I just want to confirm that. And then, I guess, is the only variable the timing of Dervalumab dosing, there's no other? The arms all look the same.

Douglas Royal Buchanan: Hey, Thanks for taking the question, obviously, congrats to Mike Sofia.

Douglas Royal Buchanan: <unk> retirement and are definitely missions.

Douglas Royal Buchanan: Deep insights and observations on the calls you have eight months to get to a functional cure.

Douglas Royal Buchanan:

Speaker Change: Yes, Jeff.

Douglas Royal Buchanan: Just a few questions.

Douglas Royal Buchanan: So I guess on the two or three trial I think I think there is a typo in the slides. It says Q48 weeks and I think Sharon.

Douglas Royal Buchanan: Eight weeks, which makes a lot more sites.

Operator: So is that the only variable? There's no difference in actual dose levels or anything else? I guess that's it. Yeah, no, thanks for the question. So, no, you're absolutely right.

Douglas Royal Buchanan: So just wanted to confirm that and then.

Operator: I guess, because the only variable that the timing of the value of our dosing arms all identical.

Speaker Change: So is that the only variable there is no difference in actual dose levels or anything else.

Speaker Change: I guess, that's my first.

Speaker Change: Yeah no. Thanks for the question so you're absolutely right. The <unk> dosing is 60 milligrams every eight weeks as we have been studying throughout our phase II program. So we'll go in and make sure that that's correct in that in the deck, but yes 60 milligrams every eight week 17 Saran for a 48 week treatment period as we've also done in some of our other.

Karen Sims: The induced saran dosing is 16 milligrams every eight weeks, as we have been studying throughout our Phase 2 program. So we'll go in and make sure that that's correct on the deck. But yes, 16 milligrams every eight weeks of induced saran for a 48-week treatment period, as we've also done in some of our other studies. And at the moment, yes, the only difference between the arms is the timing of the induced saran dose.

Karen Sims: Studies.

Karen Sims: At the moment, yes, the only difference between the arms at the timing of the <unk> as I mentioned before we obviously keep track of of the data with these trials, especially safety data, but we have no intention of changing any of the other parameters of the trial at the moment.

Karen Sims: And as I mentioned before, we obviously keep track of the data in these trials, especially safety data, but we have no intention of changing any of the other parameters of the trial at the moment. Just as mentioned, between the three arms, it's just the timing of the two Javali metas.

Karen Sims: As mentioned between the three arms, it's just the timing of the future value method.

Operator: Okay, great. And then follow up on the 101 dosing question. So it's 25 mg per day, the dose you started part two with. And then for the target engagement, I assume that was derived from, did you take circulating blood cells? Or where did you look for the target engagement?

Speaker Change: Okay, Great and then.

Operator: Follow up on the 101 dosing question. So it's 25 Megs per day. The dose you started part <unk> and then for the I guess the target engagement I assume that was derived from did you take circulating blood cells or when did you look for sort of the target engagement and the patients.

Karen Sims: Right. So in regards to the dosing of AB101 in Part 2 of the study, again, I can't comment on that. It's ongoing as we speak, and as Mike said earlier in the call, we'll be providing data for the Part 2 portion of the study in the second half of this year. And in regards to the pharmacodynamic assay, yes, it is based on peripheral blood mononuclear cells that are isolated from the subject. Okay, great. And then the last one, maybe I can't answer this either, but Tom and Nevo combo with Berentis, vaccine. Can you give us a sense of it?

Speaker Change: Right. So in regards to the dosing of 81 to one party or the study again I can't comment on that is ongoing as we speak and as Mike said earlier on the call we'll be providing data for the part two portion of this study in the second half of this year.

Karen Sims: And in regards to the Pharmacodynamic assay, yes. It is based on peripheral blood mononuclear cells that are isolated from the subject.

Karen Sims: Okay, Great and then the last one maybe cancer this either but it's on the levo.

Karen Sims: Combo with for instance.

Karen Sims: It looked like the enrollment target went up by a couple of patients, versus 20. Can you just... Tell us where enrollment stands currently in that cohort and about how many patients you can expect for the data in the second half? Thank you. Sure, absolutely.

Karen Sims: Vaccine.

Speaker Change: Can you give us a sense of it looks like the enrollment target went up by a couple of patients 22 versus <unk> versus 'twenty can you just tell.

Speaker Change: Tell us where enrollment stands currently in that cohort and about how many patients you can expect.

Speaker Change: So the data in the second half thank you.

Karen Sims: So the target enrollment was 20 subjects for that arm to be consistent with the other two arms of the study. However, as often happens in these studies, we have screening open to many sites in many countries across the globe, and we can't necessarily control the number of subjects in screening at any one time. So it just happened here that we had a couple of additional subjects that were eligible for the trial and had already completed screening.

Speaker Change: Sure absolutely. So the target enrollment was 20 subjects for that arm to be consistent with the other two arms of the study as often happens in these studies, we have screening open too many sites in many countries across the globe and we can't necessarily control the number of subjects in screening at any one time. So it just happened here.

Karen Sims: So we did allow them to enter the trial, but that's the only reason for the 22 subjects as opposed to the 20 subjects. And as I said previously, we'll be sharing the preliminary end of treatment data from that trial in the second half of this year. Yes, thank you.

Karen Sims: We had a couple of additional subjects that are eligible for the trial and had completed the screening. So we did allow them to enter the trial, but thats. The only reason for that the 22 subjects as opposed to the 20 subjects and as said previously we will be sharing the pulmonary under treatment data from that trial in the second half of this year.

Speaker Change: Okay. Thank you.

Operator: Thank you. One moment for our next question. The next question comes from Keay Nakae with Chardon. Please go ahead.

Speaker Change: Thank you one moment for our next question.

Operator: Yeah.

Keay Thomas Nakae: Our next question comes from Keay <unk> with Chardan. Please go ahead.

Keay Thomas Nakae: Oh yeah, just some follow-ups on the 101 study. In terms of the receptor occupancy, is the assay you're using standardized, or do you have to customize it? Hi, this is Mike Koeh.

Keay Thomas Nakae: Just some follow ups on one year one study.

Michael J. McElhaugh: In terms of the <unk>.

Keay Thomas Nakae: Receptor occupancy.

Michael J. McElhaugh: That you are using a standardized or do you have to customize it with us.

Michael Koeh: It's an assay we actually developed internally, so it's a proprietary assay that we use for getting that target occupancy, readout. Okay, and is the dose response you're seeing, is that consistent with what you'd hope to see? Well, you know, I would say in preclinical models, we see 80 to 100%, you know, receptor occupancy. So, that gave us full efficacy for us. So I think, you know, what we're seeing in the clinical study is very encouraging.

Michael J. McElhaugh: Hi, This is Mike.

Michael Koeh: It's an assay, we actually developed internally so it's a proprietary assay that we use.

Michael Koeh: For getting that target.

Michael Koeh: Occupancy.

Michael Koeh:

Michael Koeh: Rudolf.

Michael Koeh: Okay.

Michael Koeh: Is the.

Michael Koeh: The dose response Youre seeing.

Michael Koeh: Is that.

Michael Koeh: Consistent with what you had hoped to see.

Michael Koeh: Okay.

Michael Koeh: Well I would say in preclinical models, we see 80% to 100%.

Michael Koeh: Receptor occupancy.

Speaker Change: So okay.

Michael Koeh: Yes.

Michael Koeh: For efficacy for us so I think.

Michael Koeh: What we're seeing in the clinical study is very encouraging to us.

Michael Koeh: Okay, and then in the multi-sending dose part of the study. Just remind me again, what's the dose frequency, how often is it? So it's a total dose duration of seven days, and we do have flexibility within that arm to dose every day or anything different than that, depending on how the data reads out. So, you know, it could be a daily dose or it could be every other day or every third day. You know, that part will be determined as we evaluate the safety PK and PD data that comes in from the different arms of the trial. But it's a seven day maximum duration.

Michael Koeh: Okay, and then in the <unk>.

Michael Koeh: Ascending dose part of the study.

Michael Koeh: Just remind me again.

Michael Koeh: Dose frequency is how often is it.

Michael Koeh: So it's a total dose duration of seven days and we do have flexibility within that arm to dose every day or anything different than that depending on how the data reads out so it could be a daily dose it could be every other day every third day that part will be determined as we evaluate.

Michael Koeh: The AC PK and PD data that comes in from the different arms of the trial, but has a seven day maximum duration.

Karen Sims: Okay, and when do you expect to be able to advance to part three of the study? So it really depends on how these multiple sending dose arms proceed in the healthy subjects. So really, we just need sufficient safety PK and PE data to feel confident to move into that third portion of the trial and to choose a dose to initiate that part of the trial that we think will have impact in these chronic hepatitis B subjects. So, you know, again, it just depends on the progression of part two of the study. But it is, as we've said earlier, an integrated protocol.

Speaker Change: Okay, and when do you expect to be able to advance into part three of the study.

Karen Sims: Right. So it really depends on how these multiple ascending dose arms are proceed in the healthy subjects. So really we just need sufficient again safety PK and PD data to feel confident to move into that third portion of the trial and to choose a dose to initiate that part of the trial that we think will have a habit.

Karen Sims: Impact in these chronic hepatitis b subjects so.

Karen Sims: It just depends on the progression of part two of the study, but it is that we had.

Karen Sims: So, part three of the study is already approved. And, you know, we would be able to move on, you know, as soon as we are ready with the data. Okay, thanks.

Karen Sims: Said earlier, an integrated protocol. So the part three of the study is already approved.

Karen Sims: Would be able to move on as soon as we are ready with the data.

Speaker Change: Okay. Thanks.

Operator: Thank you. I'm showing no further questions at this time. I'd now like to turn it back to management for closing remarks. Great, thank you.

Speaker Change: Q I am showing no further questions at this time.

Speaker Change: I'd now like to turn it back to management for closing remarks.

Operator: Thanks everyone for joining us this morning. We appreciate your continued interest in and support of Arbutus, and we look forward to providing updates to progress the development of our HPV assets. Operator, that concludes our call. Thank you for your participation in today's conference. This concludes the program. You may now disconnect. [inaudible] ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? [inaudible] ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? Good day and thank you for standing by.

Speaker Change: Great. Thank you. Thanks.

Speaker Change: Thanks, everyone for joining us. This morning, we appreciate your continued interest in and support of our <unk> and we look forward to providing updates super aggressive the development of our HBV assets operator that concludes our call.

Operator: Welcome to the Arbutus Biopharma 2024 First Quarter Financial Results and Corporate Update Conference Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press * one on your telephone. You will then hear an automated message advising your hand is raised.

Lisa M. Caperelli: To withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Lisa Caperelli, Vice President of Investor Relations. Please go ahead.

Lisa M. Caperelli: Thank you, Andrea. Good morning, everyone, and thank you for joining Arbutus's first quarter 2024 financial results and corporate update call. Joining me today from the Arbutus executive team are Mike McElhaugh, interim president and chief executive officer, Dr. Karen Sims, chief medical officer, David Hastings, chief financial officer, and Dr. Mike Sofia, chief scientific officer. Mike McElhaugh will begin with a corporate update, followed by Karen, who will review our ongoing clinical programs. Dave will then provide a review of the company's first quarter 2024 financial results.

Speaker Change: Thank you for your participation in today's conference. This concludes the program you may now disconnect.

Michael J. McElhaugh: After our prepared remarks, we will open the call for Q&A. Before we begin, I'd like to remind you that some of the statements made during the call today are forward-looking statements, which are subject to a number of risks and uncertainties that may cause our actual results to differ materially, including those described in our annual report on Form 10-K, our quarterly report on Form 10-Q, which will be filed today, and from time to time in our other documents filed with the SEC. With that, I'll turn the call over to Mike McElhaugh. Mike?

Karen Sims: Thanks, Mike. And good morning, everyone. As Mike mentioned, our approach to developing a functional cure for patients with chronic hepatitis B involves reducing surface antigen, suppressing HBV DNA, and boosting the immune system. And our clinical trials conducted to date have been shown to reduce HBV DNA in untreated patients and reduce surface antigen when given both with and without ongoing standard of care in eukotherapy. In addition, evidence of HPV-specific T-cell reawakening has been observed in some patients undergoing treatment with induced ORAM.

Michael J. McElhaugh: Thanks, Lisa. Good morning, everyone, and thank you for joining us today, one announcing the end-of-year retirement of our co-founder and chief scientific officer, Dr. Mike Sofia, and one with our first quarter of 2024 financials and a corporate update. I want to pass the call to Mike Sofia to address his retirement.

Karen Sims: To further boost the immune system, we designed our phase 2a trials to evaluate induced RAN in combination with one of three immunomodulatory approaches, interferon, a therapeutic vaccine, or a checkpoint inhibitor targeting the PD-1, PD-L1 axis. Two ongoing phase 2A clinical trials, AB729201 and AB729202, are evaluating Induceran in combination with Interferon and in combination with a therapeutic vaccine As Mike said, both of these Phase IIa trials are on track to report end-of-treatment data at the ESL Congress in June.

Michael J. Sofia: Thanks Mike, and good morning everyone. Today I am announcing my decision to retire as Chief Scientific Officer at Arbutus, effective the end of this year. I will continue in my full capacity as CSO until that time. Since co-founding Arbutus more than 10 years ago, the company has made incredible strides in its research and clinical efforts. We have built an organization of dedicated individuals who are passionate about our mission to cure HPV. I continue to believe that Arbutus is on the correct path to developing a functional cure for the millions of patients living with HPV.

Karen Sims: Note that we also amended the AB-729-202 trial to evaluate the addition of the PD-1 checkpoint inhibitor antibody Volumab to the induced Niran and VTP-300 combination. We expect preliminary end-of-treatment data from that cohort in the second half of this year. Today, we announce that we have initiated patient screening in our third phase 2A clinical trial, AB729203, which is evaluating abducerin in combination with Dervalumab, an antipedial monoclonal antibody. While all of these Phase IIa trials are geared towards finding the right immune modulator to combine with induced ORAN, the AB729-203 trial with Dervalumab is specifically intended to evaluate how we can use checkpoint inhibition in combination with induced ORAN to boost HPV-specific immune responses.

Michael J. Sofia: My lifelong goal has been to discover medicines that improve patients' lives. Over my 38-year career in pharma and biotech, one of my great successes was the discovery and development of sofosbuvir, the backbone of curative therapies for hepatitis C, which has already cured millions of patients globally.

Karen Sims: This trial will inform upcoming combinations with our proprietary oral small molecule PD-L1 checkpoint inhibitor, AB101. With that in mind, I'd like to provide more information regarding the AB729-203 trial design. AB729203 is an open-label, multi-sensor, phase 2a clinical trial evaluating the safety, tolerability, antiviral, and HPV-specific immunologic activity of imduceran and ongoing Duke therapy in combination with Dervalumab, an approved anti-PD-L1 monoclonal antibody in patients with chronic hepatitis B. We intend to enroll 30 virologically suppressed patients into three separate cohort

Michael J. Sofia: Learnings from the HCV story spurred me on to find a cure for the more challenging problem, HPV. This led to the founding of Arbutus, where we have been able to build a world-class team uniquely positioned to potentially transform the HPV treatment landscape with drug candidates like Imduciran and AB101. Throughout my more than 10 years at Arbutus, I've enjoyed tackling the many challenges that drug discovery and development bring, collaborating with my colleagues, and mentoring many of the scientists. I am confident that this passionate and dedicated team will continue to do great things. I have great pride in what we have been able to accomplish at Arbutus.

Karen Sims: All patients will receive 60 milligrams of Imduceran every eight weeks with their ongoing Duke therapy for 48 weeks and will receive two doses of Dervalumab at pre-specified times during the Imduceran treatment period that will differ by cohort.

Michael J. Sofia: I look forward to following the future successes as the company advances its mission and finds a cure for HPV. Thank you, and back to Mike. Thanks, Mike, and thanks for everything you've done for Arbutus and our shareholders. I'm sure I speak for all employees when I say it's been an honor to work with you.

Karen Sims: After completion of treatment, all patients will be assessed for eligibility to discontinue new therapy and will be followed for an additional 24 to 48 weeks. The endpoints for this clinical trial include safety and changes in surface antigen from baseline during the treatment and follow-up period. This trial allows us to explore the optimal timing of checkpoint inhibitor dosing in the context of surface antigen reduction during ongoing induced trans treatment. Now moving on to our proprietary oral small molecule checkpoint inhibitor, AB101, that is differentiated from monoclonal antibodies, such as drivalumab and nivolumab, in the following ways based on our preclinical testing.

Karen Sims: First, AB101 is liver-centric, meaning it preferentially reaches the liver and has a high liver-to-plasma ratio, thus minimizing systemic exposure and reducing the chance of immune-related adverse events seen with monoclonal antibodies. Second, AB101 has typical small molecule pharmacokinetics and therefore a much shorter duration of effect than long-acting antibodies, thus allowing for the potential to modify the dose or dosing interval to maximize effect or to stop dosing to quickly mitigate any safety concern. Third, AB101 acts through a novel mechanism of action differentiated from antibodies. It binds to PD-L1 on the surface of cells, causing dimerization and internalization of the PD-L1 protein, followed by degradation within hours.

Michael J. McElhaugh: While MDU-SIREN has shown activity in all three of these components in clinical trials conducted to date, we know a combination of agents is necessary to cure this challenging disease. I'll turn the call over to Karen shortly to walk through preliminary data from our Phase Ia-Ib clinical trial with AB101 and to provide an overview of our third Phase IIa clinical trial that is evaluating the combination of Induciran and Drevalumab, a PD-L1 monoclonal antibody that has begun screening patients.

Karen Sims: Squashing out the drug results in full reconstitution of PD-L1 on the cell surface and restoration of PD-L1 function within days, unlike antibody therapy, where the duration of receptor occupancy and the PD effect is maintained for weeks with no way to reverse it. It is for these reasons that we are excited about the potential of AB101 and HBV and are advancing our AB101 clinical program, which is currently evaluating AB101 in a double-blind, randomized, placebo-controlled Phase Ia-Ib clinical trial known as AB101-001.

Michael J. McElhaugh: Currently, we have two phase 2a combination clinical trials, the AB729201 trial, which includes the addition of interferon, and the AB729202 trial, which includes the addition of Berynthes Biotherapeutics Immunotherapeutic VTP300. These trials are intended to provide data on the safety and efficacy of Induceran as a cornerstone therapy and to help us identify an optimal combination treatment that we can advance into This quarter, we will report end-of-treatment data from these two Phase 2a trials with Imdusiran, which could potentially include patients who achieve undetectable surface antigens.

Karen Sims: This trial is designed to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of AB101. The trial consists of three parts, starting with single and multiple ascending doses in healthy subjects and culminating with multiple doses in patients with chronic HBV. In Part 1, which is the single ascending dose portion of the trial, we have enrolled four sequential cohorts of eight healthy subjects each to date. Within each cohort, six subjects received AB101, and two subjects received placebo.

Karen Sims: After review of safety, PK, and PD data, AB101 dose levels were increased in each subsequent cohort up to 25 milligrams. The data from Part 1 show that AB101 is generally well-tolerated with evidence of dose-dependent receptor occupancy. In the 25-milligram cohort, five of the six subjects had test samples that were evaluable for receptor occupancy, and all five of these subjects showed evidence of PD-L1 receptor occupancy between 50 and 100 percent, indicating that AB101 is interacting with its intended target. One subject in this cohort was excluded from the PD evaluation as their samples could not be analyzed.

Michael J. McElhaugh: We are happy to report that two abstracts, including data from these Phase IIa clinical trials, were accepted for presentation at the ESL Congress, which takes place in early June in Milan, Italy. We will provide more details on those abstracts at a later date. With that, I'll turn the call over to Karen to provide an overview of the AB-729-203 clinical trial and discuss the AB-101 phase one preliminary data. I'll come back at the end of the team's prepared remarks to provide an update on our LNP litigation before we move into Q&A. Karen?

Karen Sims: We are now in Part 2 of this trial, where cohorts of healthy subjects are receiving multiple ascending doses of AB101. Our goal is to move as quickly as possible into Part 3, which will enroll patients with chronic hepatitis B. We anticipate announcing preliminary data from Part 2, the multiple ascending dose portion of this trial in healthy subjects, in the second half of this year. We believe that the immune checkpoint pathway plays an important role in HPV-specific immune tolerance and in T-cell activation, and the addition of a checkpoint inhibitor in combination with induced RAN could potentially further enhance HPV-specific immune responses. With that, I'll turn the call over to Dave Hastings for a brief financial update. Dave?

David C. Hastings: We still expect our 2024 net cash burn to range from between $63 to $67 million, excluding any proceeds from our ATM program. In April 2024, we received an additional $22.4 million in net proceeds from sales under our ATM program. And now importantly, we believe our cash runway is sufficient to fund our operations through the second quarter of 2026. So, in closing, we have a strong financial position to advance our mission of developing our HPV assets to provide a functional cure for chronic HPV. With that, I'll turn the call back to Mike. Thanks, Dave.

Karen Sims: [music].

Michael J. McElhaugh: With today's update, we have achieved most of our first half of 2024 key milestones, including reporting preliminary data from the AB 101-001 Phase 1a-1b clinical trial and initiating the Phase 2a clinical trial with MDU-SIREN and your value map. We look forward to reporting data from the AB-729-201 and AB-729-202 Phase IIa clinical trials at ESL in June. In the second half of this year, we anticipate preliminary end-of-treatment data from the Novolumab arm of the 202 trial and preliminary multiple ascending dose data from healthy subjects in the AB-101-001 trial.

Michael J. McElhaugh: 2024 is off to a strong start, and it wouldn't be possible without the dedication of my Arbutus colleagues. I would like to take this opportunity to thank all of them for their hard work to advance our pipeline. Before turning the call over to Q&A, I'd like to provide a brief update on the ongoing patent infringement lawsuit, specifically the lawsuit against Moderna. As you may recall, on February 8th of this year, there was a claim construction hearing, also commonly referred to as the Markman hearing, where the court heard each party's interpretation of the construction of claims in the dispute of patents. The court issued its order on April 3rd, in which it agreed with our position on most of the disputed claim terms.

David C. Hastings: Okay.

Michael J. McElhaugh: The litigation process continues to move forward. Fact discovery is ongoing, and next steps include expert reports and depositions. The court has set April 21st, 2025 as the trial date for this case, although that date is subject to change. The Pfizer BioNTech lawsuit is ongoing, and a date for the claim construction hearing for that case has not yet been set. We will continue to protect and defend our intellectual property, including our LNP delivery technology. All of our scientists take great pride in the intellectual property they develop, which takes great effort, time, resources, and expense.

Michael J. McElhaugh: Okay.

Yuchen Ding: Thanks for taking our questions. Two, if I may, on the pipeline, you guys have a few phase two trials with, you know, a lot of different combinations going on, but when do you think we can get any functional cure signals? And is that a 2025 type of event, or can we get some data later this year? And then, number two, you know, I, you know, I appreciate you starting a new phase two with DERVA, but, you know, I'm just curious, how much more data do you think you'll need from your hepatitis B trials before you can start phase three? I'm just wondering what the Gating Factor here is.

Michael J. McElhaugh: Is it waiting for AB 101 to show some combo data or data from the new DERVA study, which is essentially a one-year treatment and a one-year follow-up? So I'm just wondering what the gating factor is there. Thank you. Good morning, Dennis. Thanks. Thanks for the question. So Karen, do you want to handle Dennis's first question on, Functional Cure? Functional Cure, excuse me, yes. Functional Cure. Yeah, sure, absolutely.

Karen Sims: So, you know, Dennis, as you know, as you just stated, these trials do take some time, including the treatment period and the extended follow-up period. And as you know, Functional Cure signals can't be assessed until subjects are at least six months off of all treatment. So that is ongoing in both of our Phase 2 studies at the moment, both the 201 Interferon study and the 202 study in combination with, for instance, this VTP-300.

Yuchen Ding: Okay.

Michael J. McElhaugh: And then on to the second question, which was in regard to ValueMab and when we might be able to start a follow-on trial. I think the answer to that question, Dennis, is it's going to depend on what we see from our existing ongoing studies, right? So, yes, we're starting a new trial, and yes, we think that will be valuable in helping to inform how we think about the addition of AB101 to Induciran.

Michael J. McElhaugh: But as Karen just mentioned, we have some trials ongoing, which could, of course, produce interesting data, which could then lead to follow-on studies. So I don't think that it's a situation where we need to wait until we have the full picture from all of these ongoing trials before we decide what we're going to do to move forward.

Speaker Change: Thank you.

Karen Sims:

Operator: Thank you. One moment for our next question. Our next question comes from Ed Arce with H.C. Wainwright. Please go ahead. Hi, good morning, everyone.

Ed Arce: This is Thomas Yip asking a couple of questions for Ed. Thank you for taking the questions. So, first, perhaps following up with the previous question, just moving forward and doing a surround. What would the next phase, you know, a Phase 2B or a Phase 3 study, would that be expected to evaluate group serine as a monotherapy or in combination, or perhaps both? So, Thomas, good morning. Thank you. This is Mike.

Michael J. McElhaugh: Okay.

Karen Sims: For the new phase 2a study with the viral map, can you discuss the rationale behind different dosing intervals for the viral map and what is the significance due to analyzing these different dosing intervals? Yeah, thanks for the question, Thomas. So the idea here is evaluating the extent of checkpoint inhibition that's necessary to try to induce that HPV specific immunity. And as I'm sure you're aware, the use of checkpoint inhibitor therapy in oncology is a much different dosing regimen and much different dosing level. So it's very high doses over repeated cycles for weeks to months, and with that comes a safety profile that may not be optimal in patients with chronic hepatitis B.

Operator: Okay.

Karen Sims: So what we're looking to do is strike the appropriate balance between having a regimen that's safe and well tolerated for these patients with chronic hepatitis B, as well as trying to understand exactly when we need to intervene on the checkpoint inhibitor axis in the context of the surface antigen reduction that we see with induced saran. So that's the idea behind the trial is, is it best to inhibit the checkpoint axis during the acute decline of surface antigen, or is it best to inhibit it after surface antigen has reached a nadir, somewhere in between, and, you know, doing that at multiple time points. So that's the idea behind the trial is really to strike that balance between optimal immunomodulatory effects and maintaining a very good safety profile for this patient population. understood.

Karen Sims: Thank you. And perhaps one last question for AB 101. After completing the multi-ascending dose phase of the ongoing phase one study, what's the next step for the program? Would that be looking at a condom study in HPV, or are there other areas that AB 101 can have potential in?

Michael J. McElhaugh: Okay.

Karen Sims: Sure, yes, thanks for the question. Again, just to clarify, so the current study is a three-part study, so single doses in healthy subjects, then multiple doses in healthy subjects, and then we move seamlessly into multiple doses in patients with chronic hepatitis B in combination with new therapies. So we need to complete those different portions of the trial to understand the safety profile, the pharmacokinetic profile, and the PD profile of AB101 to be able to enter that next phase of studies.

Karen Sims: But certainly, you can imagine after completion of the phase one study, the next goal would be to put it in combination with induced saran in a phase two study as quickly as possible. Understood. Thank you again for taking all the questions and looking forward to the EZO Daily Readout. You're welcome, Thomas.

Karen Sims: Okay.

Operator: Thank you. Thank you. One moment for our next question. Our next question comes from Brian Skorney with Baird. Please go ahead. Hey guys, thanks for taking our question and congratulations and best wishes to Mike. This is Charlie on behalf of Brian.

Brian Peter Skorney: So, just a couple from us. Just wondering when you're thinking about dosing with AB-101, it sounds like so far you've seen good safety data, but I just would be curious if you're kind of thinking of 25 migs as a cap in the MAD as well. And then, you know, are you, when you're thinking about this, the Dervalumab trial, have you seen anything from the Nevo combination so far that might be playing into your thinking on different timings? And then, just one more on an early stage asset in the space: what are your thoughts on ALPK1 agonism, if you have any at this point? Thank you so much. All right. So, Charlie, good morning.

Karen Sims: Yes.

Karen Sims: Thanks for the question. So, Karen, why don't you handle the question with regard to AB101 and the NEVO-related to Dravalumab question? Yeah, sure. Absolutely.

Operator: Yes.

Karen Sims: It's just, you know, the data we have available to share with you today. So, and in terms of the Nevolumab data coming out of the 202 study, obviously, I can't comment on that. You know, we provided guidance that we'll be sharing the preliminary end-of-treatment data at the end of the year, the second half of this year. So, you know, that data I can't comment on, but certainly, you know, we look at all of our trials holistically and, you know, certainly, you know, would, as Mike said earlier, move forward or, you know, adapt as we see the data emerging from our trials. But yeah, to date, I can't comment on anything regarding the Nevolumab arm in the 202 study. And then, Mike, do you want to handle the last question?

Brian Peter Skorney: Yes.

Michael J. McElhaugh: Yeah, on the ALPK1 question, yeah, we're aware that an abstract just came out from EASL on that. Frankly, it just came out, so we are, you know, we'd be interested in looking at the abstract more clearly, more fully, and obviously seeing the presentation at EASL to get a full understanding of the target. Gotcha. Great. Thanks so much for the questions, guys. Thanks, Charlie.

Operator: One moment for our next question. Our next question comes from Rory Buchanan with Citizens JMP. Please go ahead. Hey, thanks for taking the questions. Obviously, congratulations to Mike Sofia on the planned retirement, and it will definitely be missed. Deep insights and observations on the cause.

Karen Sims: Okay.

Douglas Royal Buchanan: You have eight months to get to a functional cure. (Inaudible) Just a few questions. So I guess in the 203 trial, I think there's a typo on the slide that says Q48 weeks, and I think Karen said every eight weeks, which makes a lot more sense. So I just wanted to confirm that. And then, I guess, is the only variable is the timing of Dervalumab dosing; there's no other, the arms all look identical. So is that the only variable?

Operator: There's no difference in actual dose levels or anything else? I guess that's it. Yeah, no, thanks for the question. So, you know, you're absolutely right.

Michael J. McElhaugh: [music].

Karen Sims: The induced saran dosing is 60 milligrams every eight weeks, as we have been studying throughout our Phase 2 program. So, we'll go in and make sure that that's correct on the deck. But yes, 60 milligrams every eight weeks of induced saran for a 48-week treatment period, as we've also done in some of our other studies. And at the moment, yes, the only difference between the arms is the timing of the induced saran dose.

Karen Sims: And, you know, as I mentioned before, we obviously keep track of the data in these trials, especially safety data, but we have no intention of changing any of the other parameters of the trial at the moment. Just as mentioned, between the three arms, it's just the timing of the two Javali Mab doses.

Karen Sims: Okay, great. And then follow up on the 101 dosing question. So it's 25 mg per day, the dose you started part two with. And then for the target engagement, I assume that was derived from, did you take circulating blood cells? Or where did you look for the target engagement?

Operator: Yes.

Karen Sims: Right. So, you know, in regards to the dosing of AB101 in Part 2 of the study, again, I can't comment on that. It's ongoing as we speak, and as Mike said earlier in the call, we'll be providing data for the Part 2 portion of the study in the second half of this year. And in regards to the pharmacodynamic assay, yes, it is based on peripheral blood mononuclear cells that are isolated from the subject. Okay, great. And then the last one, maybe I can't answer this either, but Tom and Nevo are a combo with Berenfis.

Karen Sims: [music].

Karen Sims: Vaccine. Can you give us a sense of what it looks like the enrollment target went up by a couple of patients, 22%, versus 20. Can you just explain that?

Karen Sims: Tell us where enrollment stands currently in that cohort and about how many patients you can expect for the data in the second half. Thank you.

Karen Sims: So the target enrollment was 20 subjects for that arm to be consistent with the other two arms of the study. But as often happens in these studies, we have screening open to many sites in many countries across the globe, and we can't necessarily control the number of subjects in screening at any one time. So it just happened here that we had a couple of additional subjects that were eligible for the trial and had completed screening. So we did allow them to enter the trial, but that's the only reason for the 22 subjects as opposed to the 20 subjects.

Karen Sims: And as I said previously, we'll be sharing the preliminary end of treatment data from that trial in the second half of this year. Okay, thank you. Thank you. Please take a moment for our next question. The next question comes from Keay Nakae with Chardon. Please go ahead, yeah just some follow-ups on the 101 study. In terms of the receptor occupancy, is the assay you're using standardized or do you have to customize it? Hi, this is Mike Kaye.

Michael Koeh: It's an assay we actually developed internally, so it's a proprietary assay that we use for getting that target occupancy, readout. Okay, and is the dose response you're seeing consistent with what you'd hope to see? Well, you know, I would say in preclinical models, we see 80 to 100%, you know, receptor occupancy.

Karen Sims: Hum.

Michael Koeh: So, that gave us, you know, full efficacy for us. So I think, you know, what we're seeing in the clinical study is very encouraging. Okay, and then in the multi-sending dose part of the study. Just remind me again, what's the dose frequency, how often is it? So it's a total dose duration of seven days, and we do have flexibility within that arm to dose every day or anything different than that, depending on how the data reads out.

Michael Koeh: So, you know, it could be a daily dose or every other day or every third day. You know, that part will be determined as we evaluate the safety PK and PD data that comes in from the different arms of the trial. But it's a seven-day maximum duration.

Karen Sims: Yes.

Karen Sims: Okay, and when do you expect to be able to advance into part three of the study? Right, so it really depends on how these multiple sending dose arms proceed in the healthy subjects. So really, we just need sufficient, again, safety PK and PE data to feel confident to move into that third portion of the trial and to choose a dose to initiate that part of the trial that we think will have impact in these chronic hepatitis B subjects.

Karen Sims: So, you know, again, it just depends on the progression of part two of the study, but it is, as we've said earlier, an integrated protocol. So, part three of the study is already approved, and we would be able to move on as soon as we are ready with the data. Okay, thanks. Thank you. I'm showing no further questions at this time. I'd now like to turn it back to management for closing remarks.

Karen Sims: Great, thank you. Thank you everyone for joining us this morning. We appreciate your continued interest in and support of Arbutus, and we look forward to providing updates to progress the development of our HPV assets. Operator, that concludes our call. Thank you for your participation in today's conference. This concludes the program. You may now disconnect.

Karen Sims: Okay.

Karen Sims: Yes.

Karen Sims: [music].

Speaker Change: And thank you for standing by welcome to the our beautiful Biopharma 'twenty 'twenty four first quarter financial results and corporate update conference call.

Karen Sims: At this time all participants are in a listen only mode. After the speaker's presentation, there will be a question and answer session.

Speaker Change: To ask a question during the session you will need to press star one on your telephone you will then hear an automated message advising your hands. This race.

Karen Sims: To withdraw your question. Please press star one again please.

Speaker Change: Please be advised that today's conference is being recorded.

Speaker Change: Now I'd like to hand, the conference over to your first speaker today, Liza copper Alley, Vice President of Investor Relations. Please go ahead.

Speaker Change: Thank you Andrea good morning, everyone and thank you for joining our beautiful as first quarter 'twenty 'twenty four financial results and corporate update call. Joining me today from the our beauty executive team are Mike Michael Hall, interim President and Chief Executive Officer, Dr. Karen Simms, Chief Medical Officer, David Hey.

Karen Sims: <unk>, Chief Financial Officer, and Dr. Mike Sofia, Chief Scientific Officer.

Speaker Change: Mike Michael Hall will begin with a corporate update followed by Karen who will review our ongoing clinical programs. Dave will then provide a review of the company's first quarter 2024 financial results. After our prepared remarks, we will open the call for Q&A.

Karen Sims: Before we begin I'd like to remind you that some of the statements made during the call. Today are forward looking statements, which are subject to a number of risks and uncertainties that may cause our actual results to differ materially.

Karen Sims: <unk> those described in our annual report on Form 10-K, our quarterly report on Form 10-Q, which will be filed today and from time to time in our other documents filed with the SEC.

Speaker Change: With that I'll turn the call over to Mike Michael Hall, Mike. Thanks, Lisa Good morning, everyone and thank you for joining us today.

Karen Sims: This morning, we issued two press releases one announcing the end of your retirement of our co founder and Chief Scientific Officer, Dr. Mike Sofia, and one with our first quarter of 2020 for financials and a corporate update.

Karen Sims: Want to pass the call to Mike Sofia to address this retirement.

Speaker Change: Thanks, Mike and good morning, everyone.

Speaker Change: Today, we announced my decision to retire as Chief Scientific officer at Arbutus effect at the end of this year.

Speaker Change: I will continue with my full capacity, a CSO until that time.

Karen Sims: Since co founding are viewed as more than 10 years ago. The company has made incredible strides in its research and clinical efforts. We have built an organization of dedicated individuals who are passionate about our mission to cure HBV.

Karen Sims: I continue to believe that our beauty is on the correct path to developing a functional cure for vermilion.

Karen Sims: These are patients living with HPV.

Karen Sims: While lifeline goal has been to discover medicines that improve patients lives.

Karen Sims: Over my 38 year career with pharma and biotech one of my great successes with the discovery and development of Sofosbuvir backbone of curative therapies for hepatitis C, which is already cure millions of patients globally.

Karen Sims: Learnings from the HDD storage spurred me towards finding a cure for the more challenging problem HBV.

Karen Sims: This led to the founding of our viewed us where we have been able to build a world class team uniquely position to potentially transform the HBV treatment landscape with drug candidates like <unk> and may be one on one.

Karen Sims: Throughout more by more than 10 years at are viewed as I've enjoyed tackling the many challenges that drug discovery and development brings collaborating with my colleagues and mentoring many of the scientists tier.

Karen Sims: I am confident this passionate and dedicated team will continue to do great things.

Karen Sims: A great pride in what we've been able to accomplish that are viewed as look forward to following the future successes as the company advances its mission and finding a cure for HBV.

Speaker Change: Thank you and back to Mike.

Speaker Change: Thanks, Mike and thanks for everything you've done for our viewers and our shareholders I am sure I speak for all employees when I say, it's been an honor to work with you. We all wish you the best in your retirement.

Karen Sims: Now onto our Q1 financial and corporate update press release that we issued today announcing significant achievements made in advancing our pipeline in pursuit of developing a functional cure for patients with HBV and driving value for our company.

Karen Sims: We believe our two proprietary clinical assets in HBV induced saran, our RNA therapeutic in <unk> hundred one our oral small molecule PD lone checkpoint inhibitor has the potential to deliver on our three pronged approach to functionally cure chronic HBV, which involves reducing surface antigen depressing HBV.

Karen Sims: <unk> DNA and boosting the immune system.

Karen Sims: <unk> has shown activity in all three of these components in clinical trials conducted to date, we know a combination of agents are necessary to cure this challenging disease.

Karen Sims: I'll turn the call over to Karen shortly to walk through preliminary data from our phase <unk> clinical trial with <unk> 101, and to provide an overview of our third phase Iia clinical trial that is evaluating the combination combination of inducer and Andrew value Mab, a PD lone monoclonal antibody, which has begun screening patients.

Karen Sims: Currently we have two phase Iia combination clinical trials. The <unk> 79, 201 trial, which includes the addition of interferon and the 79 202 trial, which includes the addition of Brent This biotherapeutics immuno therapeutic <unk> 300. These trials are intended to provide.

Karen Sims: Data on the safety and efficacy of inducer and is a cornerstone therapy and to help us identify an optimal combination treatment that we can advance into later stage clinical trial.

Karen Sims: This quarter, we will report end of treatment data from these two phase III trials with <unk>, which could potentially include patients who achieved undetectable surface antigen.

Karen Sims: As we previously stated achieving undetectable surface antigen in either of these two phase III clinical trials would be an important validation of <unk> role as a cornerstone in potentially achieving a functional cure for patients with chronic HBV.

Karen Sims: We're happy to report that two abstracts, including data from these phase III clinical trials were accepted for presentation at the Easel Congress, which takes place in early June in Milan, Italy, We will provide more details on those abstracts at a later date.

Karen Sims: With that I'll turn the call over to Karen to provide an overview of the AB 790, <unk> hundred three clinical trial and to discuss the <unk> 101 phase one preliminary data I'll come back at the end of the team's prepared remarks to provide an update on our LNP litigation before we move into Q&A Karen.

Speaker Change: Thanks, Mike and good morning, everyone as Mike mentioned, our approach to developing a functional cure for patients with chronic hepatitis b involves reducing surface antigen suppressing HBV DNA and boosting the immune system and our clinical trials conducted to date in <unk> has been shown to reduce HBV DNA in untreated patients and reduce surface.

Karen Sims: And when given both with and without ongoing standard of care in Nuc therapy and.

Karen Sims: In addition evidence of HBV specific T cell reawakening has been observed in some patients undergoing treatment with <unk>.

Karen Sims: To further boost the immune system, we designed our phase Iia trial to evaluate <unk> in combination with one of three immuno modular Tory approaches.

Karen Sims: Interferon, a therapeutic vaccine or checkpoint inhibitor targeting the PD, one PD lone access.

Karen Sims: Our ongoing phase Iia clinical trial, 80% 79, 201, and 790 <unk> are evaluating <unk> in combination with interferon and in combination with a therapeutic vaccine respectively.

Karen Sims: As Mike said both of these phase III trials are on track to report end of treatment data at Eagle Congress in June.

Karen Sims: Note that we also amended the <unk> two trial to evaluate the addition of the PD one checkpoint inhibitor antibody Nikola map to the induced <unk> and BCP 300 combination.

Karen Sims: We expect preliminary ended treatment data from that cohort in the second half of this year.

Karen Sims: We announced that we have initiated patient screening in our third phase Iia clinical trial, <unk>, three which is evaluating <unk> in combination with their value add and anti PDL one monoclonal antibody.

Karen Sims: While all of these phase III trials are geared towards finding the right immune modulator to combined with Easter in the <unk> 790, <unk> III trial with <unk> is specifically intended to evaluate how we can use checkpoint inhibition in combination with MDA saran induced HBV specific immune responses.

Karen Sims: This trial will inform upcoming combination with our proprietary oral small molecule PD, one checkpoint inhibitor <unk>.

Karen Sims: With that backdrop I'd like to provide more information regarding the <unk> 79, 203 trial design.

Karen Sims: 790, <unk> is an open label Multicenter phase Iia clinical trial evaluating the safety Tolerability antiviral and Hps is specific immunological activity of <unk> and ongoing <unk> therapy in combination with your value map and approved anti PDL, one monoclonal antibody in patients with <unk>.

Karen Sims: Like hepatitis B we.

Karen Sims: We intend to enroll 30 virological suppressed patients into three separate cohort all.

Karen Sims: All patients will receive 60 milligrams of <unk> every eight weeks with their ongoing nuc therapy for 48 weeks and we will receive two doses of their value math at pre specified time during the end user and treatment period that will differ by cohort.

Karen Sims: After completion of treatment all patients will be assessed for eligibility to discontinue nuc therapy and will be followed for an additional 24 to 48 weeks.

Karen Sims: The endpoints for this clinical trial include safety and changes in surface antigen from baseline during the treatment and follow up period.

Karen Sims: But this trial allows us to explore the optimal timing of checkpoint inhibitor dosing in the context of surface antigen reduction during ongoing <unk> treatment.

Karen Sims: Now moving on to our proprietary oral small molecule checkpoint inhibitor AB 101 that is differentiated from monoclonal antibodies, such as <unk> and <unk> in the following ways based on our preclinical testing.

Karen Sims: First <unk> 101 is liver centric, meaning it preferentially traffics to the liver and has a high liver to plasma ratio, thus minimizing systemic exposure and reducing the chance of immune related adverse events seen with monoclonal antibodies.

Karen Sims: Second <unk> 101 has typical small molecule pharmacokinetics, and therefore, a much shorter duration of effect and long acting antibodies.

Karen Sims: Allowing for the potential to modify the dose or dosing interval to maximize effect or to stop dosing to quickly mitigate any safety concern.

Karen Sims: Third 80, 101 acts through a novel mechanism of action differentiated from antibody.

Karen Sims: <unk> PDL, one on the surface of cells, causing dimerization and internalization of the PD lone protein followed by degradation within hours.

Karen Sims: So flushing out of the drug results in full reconstitution of PDL, one on the cell surface and restoration of PD lone function with D. Within days, Unlike antibody therapy for the duration of receptor occupancy PD effect is maintained for weeks with no ways to reverse it.

Karen Sims: It is for these reasons that we're excited about the potential of <unk> 101 in HBV and are advancing our <unk> hundred one clinical program, which is currently evaluating <unk> hundred one in a double blind randomized placebo controlled phase <unk> clinical trial known as <unk> 101 001.

Karen Sims: This trial is designed to investigate the safety Tolerability pharmacokinetics and pharmacodynamics of AED 101.

Karen Sims: The trial consists of three parts, starting with single and multiple ascending doses in healthy subjects and culminating with multiple doses in patients with chronic HBV.

Karen Sims: In part one which is the single ascending dose portion of the trial, we have enrolled four sequential cohorts of eight healthy subjects each to date within a cohort six subjects received <unk> 101, and two subjects received placebo and after review of safety PK and PD data <unk> 101 dose levels were increased in each subsequent.

Karen Sims: <unk> cohort up to 25 milligram.

Karen Sims: The data from part one showed that <unk> hundred one is generally well tolerated with evidence of dose dependent receptor occupancy and the 25 milligram cohort five of the six subjects has had test samples that were evaluable for receptor occupancy and all five of these subjects showed evidence of PD lone receptor occupancy between 50 and 100%.

Karen Sims: Indicating that <unk> 101 is interacting with its intended target.

Karen Sims: One subject in this cohort was excluded from the PD evaluation of their samples cannot be analyzed.

Karen Sims: We are now in part two of this trial were cohorts of healthy subjects are receiving multiple ascending doses of <unk> 101 or.

Karen Sims: Our goal is to move as quickly as possible into part three which will enroll patients with chronic hepatitis b.

Karen Sims: We anticipate announcing preliminary data from part two the multiple ascending dose portion of this trial in healthy subjects in the second half of this year.

Karen Sims: We believe that the immune checkpoint pathway plays an important role in HBV specific immune tolerance and in T cell activation and the addition of a checkpoint inhibitor in combination with <unk> could potentially further enhanced HBV specific immune responses.

Karen Sims: With that I'll turn the call over to Dave Hastings for a brief financial update.

Speaker Change: Thanks, Karen and good morning, everybody.

Karen Sims: We ended the first quarter of 2024 with approximately $138 million of cash cash equivalents and investments.

Karen Sims: <unk> to approximately $132 million as of December 31, 2023.

Karen Sims: During the quarter ended March 31, 2024, we received $21 8 million of net proceeds from the issuance of common shares under our <unk> at the market offering program.

Karen Sims: These cash inflows were offset by $19 3 million of cash use in operations.

Karen Sims: We still expect our 2024 net cash burn to range from between 63% to $67 million, excluding any proceeds from our ATM program.

Karen Sims: In April 2024, we received an additional $22 4 million in net proceeds from sales under our ATM.

Karen Sims: And now importantly, we believe our cash runway is sufficient to fund our operations through the second quarter of 2026.

Karen Sims: So in closing we have a strong financial position to advance our mission of developing our HBV assets to provide a functional cure for chronic HBV.

Karen Sims: With that I'll turn the call back to Mike.

Karen Sims: Thanks, Dave with today's update we have achieved most of our first half 2024 key milestones, including reporting preliminary data from the <unk> 101, 001 phase <unk> clinical trial and initiating the phase Iia clinical trial with inducer and Andrew value map.

Karen Sims: We look forward to reporting the data from the <unk> 79, 201, and 202 phase Iia clinical trials at diesel in June.

Karen Sims: In the second half of this year, we anticipate preliminary end of treatment data from new volume add arm of the 202 trial and preliminary multiple ascending dose data from the healthy subjects and the AED 101 001 trial.

Karen Sims: 2024 is off to a strong start and it wouldn't be possible without the dedication of my <unk> colleagues I would like to take this opportunity to thank all of them for their hard work to advance our pipeline.

Karen Sims: Before turning the call over to Q&A I'd like to provide a brief update on the ongoing patent infringement lawsuit specifically the lawsuit against Medina.

Karen Sims: As you May recall on February eight of this year. There was a claim construction hearing also commonly referred to as the Markman hearing where the court heard each party's interpretation of the construction of claims and disputed patents.

Karen Sims: The court issued its order on April <unk>, and which had agreed with our position on most of the disputed claim terms. This is another important step in the ongoing litigation process and provides clarity on the interpretation of key terms and the scope of the claims.

Karen Sims: I refer you to the press release that we issued on April 4th which is available on our website and summarizes the claims related to the three patents that were presented at the markman hearing in accordance position on each claim.

Karen Sims: While this is important for us we cannot further comment or elaborate on what is in the press release, but we suggest you review the judge's opinion, which is also available on our website and his opinion. The judge provides an overview of the disputed aspects of each clean and each party's position as well as the evidence that was used to inform us.

Karen Sims: Decision, making process.

Karen Sims: The litigation process continues to move forward fact discoveries ongoing and next steps include expert reports and depositions. The court has set April 21 2025 as the trial date for this case that date is subject to change the.

Karen Sims: The Pfizer <unk> Tech lawsuit is ongoing and a date for the claim construction hearing for that case has not yet been set.

Karen Sims: We will continue to protect and defend our intellectual property, including our LNP delivery technology all of our scientists take great pride in the intellectual property, they develop which takes great effort time resources and expense operator, we're now ready to open the call for Q&A.

Speaker Change: Please standby, while we compile the Q&A roster.

Karen Sims: Our first question comes from Dennis <unk> with Jefferies. Please go ahead.

Speaker Change: Hi, good morning, Thanks for.

Speaker Change: Taking my questions two if I may on the pipeline.

Karen Sims: You guys have.

Karen Sims: A few phase two trials with a lot of different combinations going on but also anything we won't get any functional cures Sigma opened is that a 2025 type et cetera.

Karen Sims: Or can we get some data later this year.

Karen Sims: And then number two.

Karen Sims: I appreciate you're starting a new phase two with <unk>.

Karen Sims: I'm just curious how much more data do you think.

Karen Sims: Need from hepatitis B trials before you can start a phase III and I'm just wondering what is the gating factor here is the waiting for maybe 101 to show some combo data or the data from the New service study, which is.

Karen Sims: Essentially one year treatment and the one year follow up I was just wondering what the gating factors there. Thank you.

Speaker Change: Good morning, guys. Thanks for thanks for the question. So Karen do you want to handle Dennis as first question on.

Karen Sims: Functional cure excuse me, yes functional cures, yeah sure absolutely. So Dennis as you know these as you just stated these trials do take some time, including the treatment period and the extended follow up period, and as you know our functional and store signals cannot be assessed until subjects or at least six months off of all statement. So that is ongoing.

Karen Sims: In both of our phase III studies at the moment, both the tier one interferon study on the <unk> study in combination with <unk> for instance is edp 300 or so.

Karen Sims: As the data comes in and as we are able to compile that data into a meaningful data released with sufficient number of subjects, we'll certainly share that data when we can so I can't give any additional guidance to say that the trials are ongoing and we'll present the data as it becomes available.

Karen Sims: Okay and then on to the second question was in regards to the <unk> and when we might be able to start a follow on trial I think the answer to that question. Dennis says, it's going to depend on what we see from our existing ongoing studies alright. So yes, we're starting a new trial and yes, we think that will be valuable in helping to inform how we.

Karen Sims: Think about the addition of <unk> 101 to induce her in but as Karen just mentioned, we have some trials ongoing which could of course produce interesting data, which could then lead to follow on studies. So.

Karen Sims: I don't think that its a situation where we need to wait until we have the full picture from all of these trials ongoing before we decide what we're going to do to move forward. As you know the goal here is functional cure if we can deliver some functional cures in any of the ongoing studies, we will obviously be moving as quickly as possible into follow on studies.

Speaker Change: Got it thank you.

Speaker Change: One moment for our next question.

Karen Sims: Okay.

Karen Sims: Our next question comes from Ed Arce with H.

Speaker Change: H C. Wainwright. Please go ahead.

Karen Sims: Good morning, everyone. This is Thomas Yip asking a couple of questions for us. Thank you for taking my questions.

Karen Sims: So first off perhaps.

Karen Sims: Following up with.

Karen Sims: With a previous question just looking for.

Karen Sims: <unk>.

Karen Sims:

Karen Sims: With the mix.

Karen Sims: Ladies PCB or phase III study, so would that be expected to be that way.

Karen Sims: <unk> as a monotherapy.

Karen Sims: And the combination or perhaps both.

Karen Sims: So Thomas good morning. Thank you. This is Mike I think we've always said that.

Karen Sims: That we're going to have to think about combination therapy. When it comes to curing HBV, we have to hit those three pillars that we talk about frequently.

Karen Sims: So I think as we think about what our next study might look like it's definitely going to be a combination study.

Karen Sims: Understood.

Speaker Change: One question for you.

Karen Sims: With like the Sims four.

Karen Sims: With a new phase III study with the road map.

Karen Sims: Can you just can you discuss.

Karen Sims: The rationale behind that.

Karen Sims: So is it reasonable for development.

Karen Sims: This is significant.

Karen Sims: <unk> annualized is different.

Karen Sims: So if you can do both.

Speaker Change: Yeah. Thanks for the question. So the idea here is evaluating the the extent of checkpoint inhibition, that's necessary to try to induce that HBV specific immunity. So as im sure Youre aware the use of checkpoint inhibitor therapy in oncology is a much different.

Karen Sims: Dosing regimen and much different dosing levels. So it's very high doses over repeated cycles for weeks months and with that comes a safety profile that may not be optimal in patients with chronic hepatitis b. So what we're looking to do is strike the appropriate balance between having a regimen that safe and well tolerated for these patients with <unk>.

Karen Sims: Chronic hepatitis b as well as trying to understand exactly when we need to intervene on the checkpoint inhibitor axis in the context of the surface antigen reduction that we see with a noose around so that's the idea behind the trial is as best you can.

Karen Sims: Inhibits the checkpoint access during the acute decline in surface antigen is it best to inhibit after surface antigen has reached the nadir somewhere in between and doing that at multiple time points. So that's the idea behind the trial as it relates to strike that balance between optimal EMEA module Tory effects, but maintaining a very good safety profile for this patient.

Karen Sims: Population.

Karen Sims: Understood.

Karen Sims: Perhaps one last question for <unk> 101.

Karen Sims: After completing the multi ascending dose phase.

Karen Sims: Go on Phase one study.

Karen Sims: The next step for the program.

Karen Sims: B.

Karen Sims: Looking at a combination study in HBV or are there other fruit.

Karen Sims: Is that maybe 101 kind of potential.

Speaker Change: Understood. Thank you again for taking all questions.

Karen Sims: Looking forward to the easel data readouts.

Speaker Change: Youre welcome Thomas Thank you.

Speaker Change: Thank you one moment for our next question.

Karen Sims: Our next question comes from Brian <unk> with Baird. Please go ahead.

Speaker Change: Hey, guys. Thanks for taking our question.

Karen Sims: Congratulations and best wishes to Mike This is Charlie on for Brian.

Karen Sims: So just a couple from US just wondering when youre thinking about dosing with <unk> 101.

Karen Sims: It sounds like so far <unk> seen good safety data, but just would be curious if you are kind of thinking of 25 megs.

Karen Sims: Cap and the Mad as well.

Karen Sims:

Karen Sims: And then.

Karen Sims: Are you when youre thinking about this.

Karen Sims: The <unk> trial have you seen anything from the <unk> combination so far that might be.

Karen Sims: Into your thinking on different timings and then just one more on an early stage asset in this space what are your thoughts on PK. One agonism. If you have any at this point. Thank you so much.

Speaker Change: Alright, so Charlie good morning, Thanks for the questions. So Karen why.

Karen Sims: Why don't you handle the question with regards to <unk> 101 and the.

Speaker Change: The Nebo Lee to devalue that question, yes sure absolutely.

Karen Sims: The data we're sharing thus far is just the extent of dosing we've completed with <unk> 101. So it's too early to comment on the dosing that we'll be using in the next portions of the trial, we do have flexibility in the trial and all of the different arms to either increase dose decreased <unk> made changes to our dosing regimen. So 25 years as.

Karen Sims: Reported today is the highest as we tested with an excellent safety profile and good pharmacodynamic profile. So we'll be evaluating different dosing levels as we move on through the trial. So 25 isn't necessarily a cap it's just the.

Karen Sims: Data, we have available to share with you today, so and in terms of the volume Nab.

Karen Sims: <unk> data coming out of the 202 study, obviously I can't comment on that when we provided guidance that we'll be sharing the preliminary end of treatment data at the end of the year in the second half of this year. So that data I can't comment on but certainly we look at all of our trials Holistically and certainly.

Karen Sims: What as Mike said earlier move forward or adapt as we see the data emerging with our trials, but yet to date I can't comment on anything regarding the <unk> study.

Karen Sims: And then Mike do you want to handle the last question.

Karen Sims: EMEA LPTA one crush.

Karen Sims: Question.

Speaker Change: Yes, we are aware of the abstract just came out diesel.

Karen Sims: But.

Karen Sims: No.

Karen Sims: Frankly, just came out so we are.

Karen Sims: Interested in looking at the abstract more more fully and obviously seeing the presentation of diesel.

Karen Sims: Get a full understanding of the target.

Speaker Change: Got you great. Thanks, so much for the questions guys.

Speaker Change: Thanks, Charlie Charlie.

Speaker Change: One moment for our next question.

Karen Sims: Our next question comes from Roy Buchanan with citizens JMP. Please go ahead.

Karen Sims: Hey, Thanks for taking the question, obviously, congrats to Mike Sofia.

Karen Sims: Planned retirement and are definitely missions deepened.

Karen Sims: Deep insights and observations on the calls, yes, eight months to get to a functional cure.

Karen Sims: Okay.

Karen Sims: Yes.

Speaker Change: Just a few questions just so I guess on the two or three trial I think I think there is a typo on the slide it says Q48 weeks.

Karen Sims: Darren said every eight weeks, which makes a lot more sense.

Karen Sims: So just wanted to confirm that and then.

Karen Sims: I guess, because the only variable that the timing of the value of our dosing arms are identical.

Karen Sims: Is that the only variable there is no difference in the actual dose levels or anything else.

Speaker Change: That's my first.

Karen Sims: Yeah no. Thanks for the question. So, yes, youre absolutely right. The <unk> dosing is 60 milligrams every eight weeks as we have been studying throughout our phase II program. So we'll go in and make sure that that's correct in that in the deck, but yes 60 milligrams every eight week 17 surround for a 48 week treatment period as we've also done in some of our others.

Karen Sims: Studies and at the moment, yes, the only difference between the arms at the timing of the <unk> as I mentioned before we obviously keep track of of the data with these trials, especially safety data, but we have no intention of changing any of the other parameters of the trial at the moment just as mentioned between the three arms is just the timing of the future.

Karen Sims: <unk> doses.

Speaker Change: Okay, Great and then.

Speaker Change: Follow up on the 101 dosing question. So it's 25 Megs per day that dosing started part.

Karen Sims: Our <unk> and then for the I guess the target engagement I assume that was derived from did you take circulating blood cells or when did you look for sort of the target engagement and the patients.

Speaker Change: Right. So in regards to the dosing of <unk> hundred one and part two of the study again I can't comment on that is ongoing as we speak and as Mike said earlier on the call we'll be providing data for the part two portion of this study in the second half of this year.

Karen Sims: In regards to the Pharmacodynamic assay, yes. It is based on peripheral blood mononuclear cells that are isolated from the subject.

Karen Sims: Okay, Great and then the last one maybe you can answer this either but it's on the levo.

Karen Sims: Combo with brings us.

Karen Sims: Vaccine can you give us a sense of it looks like the enrollment target went up by a couple of patients 22 versus <unk> versus 'twenty can you just.

Karen Sims: Tell us where enrollment stands currently in that cohort and about how many patients you can expect for.

Karen Sims: So the data in the second half thank you.

Speaker Change: Sure absolutely. So the target enrollment was 20 subjects for that arm to be consistent with the other two arms of the study as often happens in these studies, we have screening opened too many sites in many countries across the globe and we can't necessarily control the number of subjects in screening at any one time. So it just happened here.

Karen Sims: We had a couple of additional subjects that were eligible for the trial and had completed screening. So we did allow them to enter the trial, but thats. The only reason for the 22 subjects as opposed to the 20 subjects and as said previously we will be sharing the preliminary under treatment data from that trial in the second half of this year.

Speaker Change: Okay. Thank you.

Speaker Change: Thank you thanks enrollment for our next question.

Karen Sims: Your next question comes from Keay <unk> with Chardan. Please go ahead.

Karen Sims: Just some follow ups on one year one study.

Karen Sims: In terms of the <unk>.

Karen Sims: Receptor occupancy.

Karen Sims: That you're using is standardized or do you have to customize it.

Mike: Hi, This is Mike.

Karen Sims: It's an assay, we actually developed internally so it's a proprietary assay that we use.

Karen Sims: For getting that target.

Karen Sims: Occupancy.

Karen Sims: <unk>.

Karen Sims: Rudolf.

Karen Sims: Okay and is the <unk>.

Karen Sims: Dose response Youre seeing.

Karen Sims: Is that.

Karen Sims: Consistent with what you had hoped to see.

Karen Sims: Okay.

Karen Sims: Well I would say in preclinical models, we see 80% to 100%.

Karen Sims: Receptor occupancy.

Karen Sims: So okay.

Karen Sims: Yes.

Karen Sims: For efficacy for us so I think.

Karen Sims: What we're seeing in the clinical study is very encouraging to us.

Karen Sims: Okay, and then in the <unk>.

Karen Sims: Multi ascending dose part of the study.

Karen Sims: Just remind me again.

Karen Sims: Dose frequency is how often does it.

Karen Sims: So it's a total dose duration of seven days and we do have flexibility within that arm to dose every day or anything different than that depending on how the data reads out so it could be a daily dose it could be every other day every third day that part will be determined as we evaluate the safety.

Karen Sims: PK and PD data that comes in from the different arms of the trial, but has a seven day maximum duration.

Speaker Change: Okay, and when do you expect to be able to advance into part three of the study.

Karen Sims: The impact in these chronic hepatitis b subjects.

Karen Sims: No.

Karen Sims: Again, it just depends on the progression of part two of the study, but it is we have said earlier and integrated protocol. So the part three of the study is already approved.

Karen Sims: You would be able to move on as soon as we are ready with the data.

Speaker Change: Okay. Thanks.

Karen Sims: I'm showing no further questions at this time I would now like to turn it back to management for closing remarks.

Karen Sims: Great. Thank you. Thanks.

Speaker Change: Thanks, everyone for joining us. This morning, we appreciate your continued interest in and support of our <unk> and we look forward to providing updates to progress the development of our HBV assets.

Karen Sims: Operator that concludes our call.

Karen Sims: Thank you for your participation in today's conference. This concludes the program you may now disconnect.

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