Vir Biotechnology, Inc. Price & Performance (VIR)

Thank you, and good afternoon. With me today are Doctor. Mary Ann DeBacher, our Chief Executive Officer Doctor. Mark Eisner, our Chief Medical Officer Jason Arburne, our Chief Financial Officer Doctor. Mika Durick, our Executive Vice President of Oncology will be available during the Q and A session.

Before we begin, I would like to remind everyone that some of the statements we are making today are forward looking statements. Under the securities laws These forward looking statements involve substantial risks and uncertainties that could cause our clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by such forward looking statements. These risks and uncertainties and risks associated with our business are described in the company's reports, filed with the Securities and Exchange Commission. Including Forms 10 ks, 10 Q and eight ks. Please note that any cross trial comparisons to and caution should be exercised when interpreting such comparisons. With that, I will now turn the call over to our CEO, Vir Demacher.

Thank you, Rich, and good afternoon, everyone. Thank you for joining us for our fourth quarter and full year 2024 earnings I'm truly excited to share our progress with you today. 2024 was nothing short of transformative. [indiscernible] As I reflect on the past year, I'm incredibly proud of what we've accomplished. We've made significant strides in our oncology and infectious disease programs positioning Veer Bio at the forefront of innovative therapies in these areas of critical unmet medical need. Our strategic focus on T cell engagers and hepatitis has not only yielded promising results, but has also positioned us well for future growth and value creation. This focused approach allows us allocate our resources efficiently and make meaningful progress Now let me start with our infectious disease portfolio. We are moving full steam ahead with preparations for our ECLIPSE Phase three program in hepatitis delta.

Which we expect to initiate in the first half of the year. The regulatory designations we've received U. S. FDA breakthrough therapy and fast track designations as well as EMA prime designation and orphan drug status underscore the potential impact of our combination regimen and the significant unmet medical need. We believe the market for hepatitis CLLS therapies shares characteristics with orphan diseases, including lack of efficacious treatment options, severe clinical outcomes, and the potential for value based pricing that appropriately reflects the clinical benefit our therapy may offer. Current treatment options are limited, especially in The U. S. Where there are no approved Hepatitis delta virus requires hepatitis B surface antigen to complete its lifecycle.

Our combination therapy of Tovebibart and elapseiran offers a unique approach by reducing hepatitis B surface antigen through two distinct and complementary mechanisms. So Betty Bart, an Fc engineered monoclonal antibody, is designed to block viral entry and neutralize virions While ILEPSRAM the small interfering RNA, aims to reduce hepatitis B surface antigen production by degrading HBV mRNA. This dual pronged strategy addresses both hepatitis delta and hepatitis B replication simultaneously. Potentially offering comprehensive and durable viral suppression. We believe this approach has the potential to address significant unmet need in chronic hepatitis delta, and become a new standard of care. Now turning to our exciting programs in oncology. As many of you know, we held a successful P Cell Engager Investor event on January 8, The data we presented for 818 a HER2 targeted T cell engager was very promising. We saw promising early signs of clinical activity particularly in colorectal cancer with an encouraging safety profile. Our PSMA targeted T cell engager, VER-five hundred also showed strong early results in prostate cancer. With impressive PSA responses and a favorable safety profile. The activity we observed clinically is a clear indication that our dual mass construct is being cleaved and activated as intended.

These results now across two clinical programs validate the potential of the Proxtend platform to address significant unmet needs in solid metastatic tumors. We are also making great progress with VER-fifty five twenty five our EGFR targeted T cell engager. We are on track to initiate a Phase one study in the first half of this year. Importantly, we have secured worldwide rights to the Proxtend platform in both oncology and infectious diseases. This gives us a powerful foundation for future growth. As the platform's universal Club and Play marketing technology can be applied to both existing as well as novel product. This capability not only supports our current pipeline, but also provides us with significant flexibility to expand into additional high value indications the future. In hepatitis B, we're looking forward to sharing functional Q data in the second quarter. It's important to note that we would take this program forward only with the commercialization and development partner. Our financial position remains strong with the cash runway expanding into mid-twenty twenty seven. This solid foundation is the result of our achievements since late twenty twenty three, where we significantly reduced our operating expenses and cash burn. We're maintaining a disciplined approach to capital allocation, focusing our resources on our most promising programs.

At the same time, we are actively exploring partnership opportunities to maximize the value of our broader pipeline. As you'll hear in more detail shortly, our 2024 financial results reflect both our strategic investments and our commitment to fiscal responsibility. As we look to 2025, I'm confident that our strategy sets us up for long term success and value creation. With that, I'll now turn the call over to Mark to provide an update on our clinical development program. Thank you, Mary Anne.

We've made significant progress in clinical stage programs and I'm looking forward to sharing the details with you today. Let's start with our hepatitis Delta program which continues to be a key focus for us. We're making excellent progress towards initiating our Eclipse Phase three program in the first half of this year. These studies will form the basis of our marketing applications. Before we dive into the ECLIPSE program, let me briefly recap our SOSTUS Phase two data has given us confidence to move forward with our Phase three program. We saw impressive virologic responses across multiple cohorts to provide some context when we refer to HDV RNA target not detected or TND, we mean there is no measurable presence of the virus in the blood.

This is the most stringent measure of viral suppression we can achieve with current testing methods.

In our de novo combination therapy arm, a twenty four weeks forty one percent of patients achieved HDV RNA levels below the target not detected threshold Even more impressively, this increased to sixty four percent of patients at week thirty six. In our rollover cohort, which provides our longest follow-up data we saw even more encouraging results. At week sixty, four out of five patients were eighty percent achieved target non detected levels. This suggests the potential for durable and deepening responses with our combination therapy over time.

Importantly, we also observed significant declines in hepatic surface antigen levels At week twenty four, approximately ninety percent of participants receiving the combination of Vir lopsaran achieved surface antigen levels below 10 I. E. Per ml This is a crucial finding because reducing hepatitis B surface antigen is essential for controlling hepatitis B and hepatitis D virus replication. Additionally, the combination of Tabivivuard and Vir demonstrated a favorable safety profile across all the cohorts. Our approach has garnered significant regulatory support which speaks to the potential impact of our therapy. We've received breakthrough therapy designation and fast track designation from the FDA. The EMA has granted a prime designation and orphan drug status. These designations could help accelerate our development and review process potentially bringing this much needed therapy to patients sooner. Turning to our hepatitis B program, we are looking forward to sharing functional cure data in the second quarter of this year, This functional interior data will be a crucial milestone for this program I want to reiterate that we would pursue the development of this program only with a partner. I'm very excited about the progress we've made in our infectious disease programs. We're on the cusp of potentially changing the treatment landscape for hepatitis Delta and we're looking forward to sharing our hepatitis B functional cure data.

Now let me shift gears to discuss our oncology portfolio to discuss the significant progress we've made with the ProXtend platform as Marianna mentioned, we've shared compelling data at our investor event in January and I'd like to dive deeper into those results. Before we get into the specifics of each program, let me briefly recap [indiscernible] This innovative technology allows us to create dual masked T cell engagers designed to be selectively activated in the tumor microenvironment The key advantage is the potential for a wider therapeutic window allowing for higher dosing and improved efficacy with reduced systemic toxicity. [indiscernible] The ProxDend masks are unstructured and hydrophilic. Acting as a shield to prevent T cell engagement in normal tissues expressing the target antigen. Importantly, their fluid nature also allows access to the cleavable linkers enabling efficient activation in the protease rich tumor microenvironment ProxDAN masks are universal and have been clinically validated as seen in Altuveo, an approved therapy for hemophilia. Altuveo contains three protease cleavage sites that are quickly cleaved in a high protease microenvironment of a clot during the clotting cascade.

Demonstrating the ability of the Proextend system to enable efficient and tightly regulated unmasking. We believe this approach could overcome many limitations seen with traditional unmasked T cell engagers and the validated nature of the platform gives us confidence in its potential application across our oncology programs. Let's start with the VER-five 818.

Vir HER2 targeted T cell engager. We've seen encouraging efficacy signals across multiple HER2 positive tumors particularly in colorectal cancer, At doses of four hundred micrograms per kilogram and above, we observed a thirty three percent confirmed partial response rate in colorectal cancer patients. It is important to note that these patients had exhausted all standard of care options and were heavily pretreated with many having received multiple prior lines of therapy including current two targeted treatments. Additionally, one of these three responses was observed in a patient on the every three week dosing schedule. I'd also like to highlight a compelling case we presented at our recent investor event which speaks to the potential for durable responses.

A patient with HER2 positive colorectal cancer progressed through six prior lines of therapy including HER2 targeted agents achieved a partial response. Remarkably, this response has been sustained for over eighteen months with the patient still on study as of our last data cutoff Crucially, we've observed efficacy in microsatellite stable or MSS colorectal cancer tumors, which typically are resistant to therapies. This suggests 800 and eighteen's ability to overcome the immunosuppressive tumor microenvironment in these hard to treat patients To put these results in context, it's important to note that for patients who have exhausted multiple lines of treatment, current regimens like LONSWERF plus befacizumab typically show objective response rates in the single digits.

Our early results therefore are particularly encouraging this heavily pretreated population. The safety profile of VER-five thousand eight hundred and eighteen has been favorable with no high grade cytokine release syndrome or CRS and without mandatory prophylactic corticosteroids.

We're continuing dose escalation on an every three week schedule to optimize efficacy while maintaining this favorable safety profile. We're also exploring combination strategies including with pembrolizumab, it's worth noting that VER-five thousand eight hundred and eighteen utilizes the pertuzumab binding which enables potential combination strategies with trastuzumab based therapies in an earlier line setting. Turning to VER-five thousand five hundred, our PSMA targeted T cell engager for prostate cancer, we've seen impressive early results in our ongoing Phase one dose escalation study. Among the 12 patients treated in the efficacious [indiscernible] one hundred percent experienced PSA declines with fifty eight percent achieving PSA50 response and eight percent achieving a PSA 90 response. This is particularly encouraging given the heavily pretreated nature of this population Vir the early stage of dose escalation. Like VERA-five thousand eight hundred and eighteen, VERA-five thousand five hundred in early dose escalation a favorable safety profile with minimal high grade adverse events and no grade three or higher CRS Notably, these results have been achieved without the use of prophylactic corticosteroids or anti IL-six therapies, which are often required with other T Engagers including masked T song gauges, Importantly, have not observed any cases of on target off tumor toxicities such as hearing loss which have been reported with other PSMA targeted We're continuing dose escalation and based on our favorable safety profile, we believe there's to potentially improve efficacy further.

As we move to higher doses, we expect to see deeper and more durable responses which could significantly improve outcomes for patients with prostate cancer. We're also actively exploring every three week dosing which could be a significant advantage, especially in earlier lines of therapy. This potential for less frequent dosing is supported by VERA-five thousand five hundred pharmacokinetic profile was a half life of eight to ten days.

The potential for less frequent dosing combined with the encouraging efficacy and safety profile we've observed could offer meaningful benefit to patients across various stages of prostate cancer treatment Importantly, these results have been achieved without the need for prophylactic corticosteroids or anti IL-six therapies. For VERA-five thousand five hundred and twenty five, our EGFR targeted T cell engager, we're on track to initiate the Phase one study in the first half of this year. This program has potential to address multiple high value indication including non small cell lung cancer, colorectal cancer and head and neck cancer. We're leveraging our learnings from VERA-five thousand eight hundred and eighteen and VERA-five thousand five hundred to optimize the study design and dosing Based on our experience with the Proxxtend platform, and the successes we've seen with our other T cell engagers, we're confident in our ability to achieve a broad therapeutic index with VER-five thousand five hundred and twenty five We Looking ahead, we anticipate sharing additional data from our ongoing dose escalation studies VERVER-five thousand eight hundred and eighteen and VERA five thousand five hundred.

While the exact timing is still to be announced, we expect to present more mature data at higher doses for both programs, This will include results from both weekly and every three week dosing schedules which we believe will provide valuable insights into the optimal dosing regimens for these therapies. In conclusion, I'm very excited about the progress we're making across our oncology portfolio.

The early data from our T cell engager programs are further validating the potential of the ProxDend platform demonstrating both efficacy and the ability to dose higher than traditional unmasked approaches we believe we're well positioned to redefine the treatment landscape for several challenging solid tumors, Our team remains focused on executing our clinical development plans in and unlocking full potential With that, I'll now hand the call over to Jason. Thank you, Mark.

I'm really pleased to share that our hard work on rightsizing the cost structure improving efficiencies and making thoughtful investment is paying off. Since late twenty twenty three, we've taken significant steps to streamline operations and focus on our most promising programs. We've implemented two restructurings closed two sites and deprioritize certain programs. Then in September, executed the agreement with Santa Fe to license three dual mass T cell engagers and the Pro Xtend technology. Including approximately 50 new team members from Sanofi, It significantly expanded our pipeline and brought in critical expertise in oncology, T cell engager clinical development, and masking technology.

This combined with our existing expertise in protein engineering and immunology positions us well for future growth and innovation.

During our budget process last fall, we applied further financial discipline culminating in our January 8 announcement to advance our HBV program only with a development and commercialization partner. Many of these actions have led to substantial improvements in our financial Let me highlight a few key financial metrics for 2024 compared to 2023.

R and D expenses for 2024 were $57,000,000 compared to $580,000,000 in 2023.

This decrease was achieved despite absorbing incentive fee transaction expenses related to our licensing agreement.

Excluding this one time transaction related Our R and D spending decreased by approximately $176,000,000 or about 30% year over year.

Reflecting our continued focus on cost management and program prioritization.

G and A expenses decreased to $119,000,000 in 2024 from $174,000,000 in the prior year. This significant reduction, reflecting a 32% decrease year over year was primarily achieved through multiple cost saving initiatives implemented since late twenty twenty three. As a result, our net loss for 2024 was $522,000,000 compared to $615,000,000 in 2023. Excluding the $103,000,000 Sanofi R and D transaction expense, Our net loss for 2024 was $419,000,000 representing a decline of approximately 32% from the previous year. We ended 2024 with four zero eight employees, compared to five eighty seven at the end of twenty twenty three. Representing about a 30% year over year reduction. It's important to note that the four zero eight includes approximately 50 employees who joined us from Sanofi, as part of our licensing agreement. Now turning to cash.

Our 2024 net cash consumption was roughly $532,000,000 Excluding approximately $179,000,000 of Sanofi transaction related items, The decrease to cash and investments for 2024 was approximately $354,000,000 We're starting 2025 with a strong financial position of $1,100,000,000 in cash, cash equivalents and investments. It's important to note that this $1,100,000,000 figure already excludes the $75,000,000 pending EGFR milestone. Which is currently in escrow and classified as restricted cash. Based on our current operating plan, we anticipate this will provide runway into mid 2027. As we look ahead to 2025, I want to emphasize that our capital deployment strategy remains focused on our most promising programs. Our priorities for the year are: [indiscernible] we'll accelerate ECLIPSE clinical enrollment and initiate activities toward registration. Second, we'll invest in DEER 5,500 to rapidly advance the program capitalizing on the very encouraging PSMA data, was shared in January. Third, we'll continue enrolling patients in VER-five 818, potentially leveraging the promising early data we see in HER2 positive colorectal cancer. Fourth, we'll initiate the Phase one study for VER-five 525 patients with EGFR expressing solid tumors, And finally, for our hepatitis B program, we continue to pursue a partnership strategy. We believe this approach will maximize the value of the asset while allowing us to focus our internal resources on our lead programs.

In closing, I'm confident that our $1,100,000,000 in cash will fund these priorities into mid-twenty twenty seven based on our current operating plan. This reflects our ongoing commitment to disciplined capital allocation, ensuring we have the resources to advance our key programs, while maintaining financial flexibility. With that, I'll hand it back to Rich to initiate the Q and A session.

Thank you, Jason. This concludes our prepared remarks. We will now start the Q and A section.

Please limit your questions to two per person. We can get to all of our covering analysts I'll turn it over to you, operator.

At this time, we will begin conducting our analyst Q and A session. To ask a question, like to join the queue if you have not done so already. Once you hear the operator announce your name, The first question comes from Geno Wang from Barclays. Your line is open. Hi. This is Han Ku on behalf of Jin A Wen from Barclays.

We have two questions. First one is for T cell engager.

So you are using the clear bone thinker. So can you elaborate the mechanism for the cleavage and how efficient is the cleavage in the tumor microenvironment, for instance, for the single cleavage and for dual cleavage? The second question is for HDV. So regarding the Eclipse registrational study starts in the first half of the year. So what additional steps you need to start this trial And we understand this is event driven but what is your estimated timing to complete the enrollment? Thanks.

Thank you very much for that question. I'll ask Nika to address the first one related to the mechanism of action related to cleavage of the linkers. Yes. Thank you for that question. So we believe that we're getting efficient lead cleavage for both masks. And the reasons for this is that we've seen really nice activity in both the HER2 program as well as the FTSE program, both having the double mask and both having the same Pro Xtend masking technology as well as both having the same protease linkers on both sides of the linkers. In addition to that, seeing that activity, that appears to be tumor specific as we've not seen any significant toxicity in the periphery very minimal CRS, in the absence of prophylactic life span prophylactic corticosteroids We're really seeing that tumor specific cleavage Besides that, the same exact Xtend masking technology is used in an approved drug out [indiscernible] It has the same Xtend Max and it uses three thrombin cleavage sites and it is efficiently cleaved. Three sites, in the setting of a clock, where you have efficient transduction activation, efficient cleavage and clotting as needed. As well as not having clotting in the state where there is no clotting activated clotting cascade.

So the efficiency of being able to cleave three sites there's nothing about the Xtend Max in of itself that prevents access to the cleavage sites. Three sites versus two sites versus one site, tumor microenvironment is known to have very high protease activity So we don't think that the number of sites is really an issue in terms of efficiency of cleavage. Thank you, Mika. So as to your second question, relates to additional steps before starting our ECLIPSE trial, I will ask Mark to address that.

Sure. Thank you for the question. So we are on track to initiate Eclipsa program in the first half of this year. The team is working with a high sense of urgency and excitement to get these trials up and running. We're confident that we will be able to initiate these trials in the near term and efficiently recruit patients because of the high unmet need in HQV and our very compelling Solstice Phase two data. So we're working quickly to get these studies up and running and we will provide some updated guidance at a future point. The next question comes from Paul Choi from Goldman Sachs.

Your line is open.

Hi. Thank you. Good afternoon and thank you for taking our questions.

My first question is on the 5,525 EGFR TCE program. Can you maybe And for us, a picture of what sort of patients you're envisioning for your Phase one study.

Are you going to allow sort of MET treated experienced patients or patients who have been treated with Vir event by specific be enrolled into your study? Any sort of color to understand what population you'll be there would be great. And my second question is on the hep B program. Realized that the March Vir data is coming up here next quarter fairly you sort of think about sort of go no go criteria for the future even though you plan to partner it. Can you maybe just again refresh your views on what you think is clinically meaningful here and what you think would potentially be attractive to a theoretical development partner?

Yes. Thank you, Paul. On the hepatitis B program, our go no go criteria, I'll ask Mark to address Sure. Thanks for the question, Paul.

So as you said, we will have our functional cure rate data second quarter of this year. In particular, this is going to be the functional tier data twenty four weeks off treatment. We had compelling results at the end of treatment at forty eight weeks In the surface antigen low patients, we had thirty nine percent S loss in the doublet with tepibabartan left arm and forty six percent loss in the triplets including pegylated interferon. In terms of go no go criteria, I mean what we said before is we're looking for a 30% functional cure in the triplet. Twenty percent in the doublet. Generally speaking, that's based on our KOL interactions and what could be clinically meaningful.

Think it's also maybe worth mentioning that just case of Roberson had a sixteen percent functional cure they're in Phase three based on that. So they their Phase three program will weed out early next year, but that kind of gives a little bit of context for what's been achieved so far. So we will be partnering this program and engaging with partners once we have the functional cure data and I hope gives you a little bit of context for what we're looking for.

So I can answer the EJFR question So a pretty standard first in human Phase one study.

And in such that patients must have exhausted all current standard of care to be enrolled on study. Which means that they must have exhausted standard approved drugs but we will allow for patients who may have been on any prior experimental drugs as well. So we do typically do get a smattering of different types of patients. We are enriching for patients who have EGFR as a target that's important such as lung cancer head, neck, pancreas and colorectal cancer. But other than that, we're probably going to have patients with variety of different prior treatments. The next question comes from Mike Hallis from Morgan Stanley. Your line is open.

Hey, it's Avi Novak on the line for Mike. Thank you for taking our questions. So I guess number one on 5525, given the strong safety profile you've seen in the Phase one studies of fifty eight five thousand eight hundred and eighteen and five thousand five hundred. These see a read through to 05/2025? And do you believe you can possibly more aggressively escalate doses in the upcoming Phase one study.

And then, my second question is, what are you thinking with respect to disclosing data for 05/2025? Do you think you would maybe plan to do an initial data update as you did for 05/2018 and May or wait for more mature data? Thanks.

Yes. Thank you for that question. As you know, there have been significant learnings from the HER2 program that were translated to the May program and the PSMA program could start at the higher dose and escalate more swiftly compared to the original 5,818 program. So we are expect that we will continue to learn across the clinical programs and that these learnings will benefit us also as we go into the five-five-five program. Anything you want to add there? [indiscernible] I mean, the only thing is that eGFR is broadly expressed in normal [indiscernible] Which makes it different from the PSMA program where of course there is PSMA expressed outside the prostate and in HER2 there is The UJFR is broadly expressed. So we're looking forward to this program because it will be a really vigorous test of our dual masking approach and the specificity for unmasking the tumor microenvironment whether we can achieve an excellent therapeutic index in EGFR positive tumors as Mikael alluded to before. But to Mary Anne's point, yes, I mean, the learnings from the earlier two programs have and will continue to inform 06/2025 and further programs. So we do expect to be efficient in how we conduct that.

Yes. And I might just also add in that from the HER2 program, again, in EGFR molecules, we'll use the same ProXtend technology, the same protease, Langer, etcetera. With the HER2 program, we've seen a prior naked HER2 T cell engager that had a grade four CRS at 0.5 micrograms per kg. And IL-six levels in the 10,000 picomol per ml range. Suggesting that there's plenty of normal expression of HER2 enabling that [indiscernible] But when you look at our eight eighteen map double mass molecule, our start dose was one microgram per kg, so higher than this fully unmasked HER2 drug GVR1302 that was that was in the clinic many years ago. So we do believe with that very wide therapeutic index that we've seen for for this HER2 double mask that will have give us confidence on the 5,525. The next question comes from Roanna Ruiz from Living Partners. Your line is open.

Hi. This is Maiz Ali Mohmad on for RWA. Thanks for taking our questions. But first, so given the early clinical response signals in the heavily pretreated patients, what are your thoughts of potentially moving the cell engagers into earlier lines of therapy in future trials. And also, could you elaborate on how machine learning and antibody engineering, your like background in that and those capabilities are being applied to opt optimize design and efficacy of your T cell inhibitors. [indiscernible] Thank you for that question. As to moving to earlier lines, maybe Mark can address that? Sure. So, yes, you are correct that in both the HER2 and PSMA programs. It's a basket trial for HER2, PSMA is all a castration resistant prostate cancer, but they're heavily pretreated patient population, very heterogeneous in terms of their clinical features and prior treatment history. So that is where we are starting. For the PSMA program, of course, we are interested in getting into earlier lines of treatment This is something that we will talk more about in future time, but clearly that is of interest. In terms of your question about the Daisy, machine learning and how to optimize the TCE platform, mean, I think one of the beautiful parts about this deal bringing in the Aminex platform and the people with it is that we can apply our antibody discovery Vir platform in our DAISY AI abilities to optimize the next generation of T cell engagers.

So we are using that to more rapidly identify and optimize the binders for the next generation T cell engagers. So I think there's a real synergy there between Vir viewers antibody discovery and optimization platform that's AI driven and the T cell engager platform that we now have in house.

Yes, I would just add that our protein engineering platform is really such that we start with a starting point of protein, it could be an antibody, it could be a bite or a single chain of C or whatever it might be. And then we deploy basically a compilation of different models to come up with molecules that have increased characteristics better potency, increased developability and so on. And it's a combination of both internal models and external models, so large protein models and a lot of internal data that we have generated over the years that together gives us an output that we can quickly test in biological models and that sort of feeds back into the database. The next question comes from Eric Joseph from JPMorgan. Your line is open. Hi, this is Billy on for Eric.

Thanks for taking our questions.

Quick one on the dosing frequency for the EGFR. You've pushed to go to Q3 weeks with the other two, is this something that you continue with the EGFR?

Yes. So we are are looking at both Q week and Q3 week for both the HER2 and the TSMA program. And we are planning to do the same for the EGFR. We're encouraged that the half life so far for both of our our clinical programs are very encouraging. And that for the HER2 program, appears to be safe and efficacious. At both schedules.

Great.

Thanks for taking my question.

The next question comes from Phil LeDoux from TD Good afternoon. Thanks for taking our questions. Two from us. The most common question we currently get on veer is about the expectations for dose response for 5,500 I'm sure you get that same question. Can you talk a little bit more about what gives you confidence that higher doses will [indiscernible] deeper and more durable PSA responses given that wasn't a clear dose response in the initial data. This first question Second question on the timing of the next updates for 510,818. We appreciate it's too early to give specific timing guidance, but could you speak to what you hope to have in the next update in terms of quality and quantity of data? Will you wait for some certain number of patients in the trials? Or do you want to wait for the Phase two dose? Some sense of kind of what you hope to accomplish before giving us the next update would be helpful. Thank you.

Yes. Thank you, Phil. I mean, we are really trying to assume mentioned, balanced communication of data that is really meaningful with the need to draw important conclusions as to our next steps from from the data. And as you know, both programs are in dose escalation. We just discussed, we're exploring two different dosing frequency models. We are exploring combination with PEMROD. So a lot of data that needs to read out on safety, efficacy, durability and so on. So as that data develops, As soon as we have really meaningful updates, of course, share that with you all. As it relates to the dose response, yes, we do get that question. Quite often. So either Mark or Mika, if you want to address it.

Yes. I think what we tried to emphasize in our Investor Events in last January is that this is very early in PSMA program in terms of dose escalation. We believe we've presented compelling early signs of in terms of PSMA I'm sorry, PSMA declined and excellent safety with minimal CRS and minimal toxicity. So we have a lot of room to move on the dose. So we've been escalating the dose both in QE in Q3 weeks, and we are anticipating to see deeper, more sustained efficacy as we escalate the dose in that program. The other thing maybe to mention is that we have now shown good compelling early signs of efficacy in safety of both the HER2 and PSMA program. So we're really validated, we think, the platform and the mass, dual mass nature of the platform and the specificity of our ability to unmask these molecules in the tumor while maintaining a very high safety profile.

Maybe just to mention one other thing, which was in that colorectal cancer patient we referred to today and that we presented in our investor event, in the HER2 program that when we escalate the dose from sixty to six hundred micrograms per kilo in that patient, we saw a deepening anti tumor responses. So that patient is an example of what can can happen as we escalate the dose. Now of course, the PSMA programs even earlier and we are continuing to escalate the dose, but we anticipate with higher doses we'll see better efficacy with acceptable safety.

The next question comes from Alex Shenahan from Bank of America.

Your line is open.

Hey guys. Thanks for taking our questions. Just two quick ones from us. First on 5525, apologies if this is already asked, but just on the need for steroid prophylaxis, do you think your other two assets or maybe a different approach as given the breadth of the EGFR expression And secondly, appreciate the additional preclinical mass to see targets are undisclosed, but I guess as you're approaching maximizing the value of the Pro Extend platform, in oncology, Is your development process driven more by derisk targets or areas of high unmet need maybe with a novel target. Thank you.

Yes. Thank you, Alek. Maybe I'll address the second question. So since we announced the data on January 8, it has been quite a bit of outreach as it relates to our platform. And so we have for ourselves defined a set of targets that we would believe would be highly valuable as next programs, but we also are getting educated on what some potential partners might be interested in. So we will certainly share going forward some more insight into how we are thinking about what next preclinical programs could be that really take advantage of the work stem platform because we do want to make sure we accept that out of the platform. And again, a high belief in the potential there. As it relates to the need for prophylactic cortical steroids, just clarifying that we did not use in our private program and for 05/2025, the same is true. I don't know Mark, you can add anything to that. Yes. So we've built quite a bit of confidence with the platform with the other two drugs, again, not using not having to use prophylactic steroids with really minimal CRS. Very minimal IL-six levels. So for the 05/2025, we are starting that study without any prophylactic steroids.

The next question comes from Joseph Stenger from Needham. Your line is open.

Hi, thanks for taking our questions. Financial one from us. Can you just remind us of the details of the collaboration agreement with Alnylam on the Leb Siron component, I believe it's a cost profit share, but just want to make sure the details on the cost share I guess my question is around the financial impact of this. Does Alnylam have optionality coming up for that asset and is that potential decision built into some of your OpEx and cash burn assumptions over the next few years And then as a follow-up, how does that current collaboration agreement impact your potential partnership negotiations for the HPV program.

Yes. Thank you for that question. So our collaboration agreement with Onnylam, spanning from 2017, Vir a pure financial arrangement.

So there's no operational role that Alnylam is playing in the development of North commercialization. Alnylam does have an option to either step into the program and share 50% of the cost as it relates to the the commensurate percentage of the profit or opt out and have a typical type of milestone and royalty deal. So that is an still needs to decide on. The impact on any partnership related to HBV You know, Both are possible. I mean, again, because nature of the deal with online is a pure financial one, It doesn't preclude from a large pharma partner to step in and take an operational role on the clinical development and commercial Obviously, it would be easier if there was sort of one partner for the program that's brought up possible.

Could I just add on this further details will be in the 10 ks on the Alnylam agreements. And just as you think about our runway we have sort of assumed the worst case in the shorter term, which is In the shorter term, if they opt in and do a profit share, that would potentially be upside. The next question comes from Patrick Trucchio from H. C. Wainwright.

Your line is open.

Thanks. Good afternoon. Just a couple of follow ups for me on the HDV program. I'm wondering now is more time is passed and you've had more time to kind of digest the data from Solsys, if there's been any further learning that could help inform the Eclipse program And then separately, I was just curious if you could talk more about the relative importance of demonstrating that robust reduction in HB surface antigen the hepatitis delta setting and how we should think about this reduction for combination treatment relative to the monotherapy antibody, particularly as we think about long term outcomes in this chronic treatment setting with Delta. Yes, thanks for the question. So in terms of Solstice, just to recap for everyone, I mean, we did see twenty four weeks forty one percent of patients reaching complete viral suppression or target detected twenty four weeks sixty four percent at thirty six weeks, at sixty weeks in the rollover cohort. So I think we're really seeing unprecedented levels of viral suppression of the Delta virus. So we're very excited about that and we're very keen to move into the Eclipse program Obviously, we've learned a lot about that's Delta both in terms of the data, but importantly, about the demographics of the disease, where the patients reside, And I think those learnings are really informed how we've heard site selection, investigator selection and things of that nature.

So So we're not prepared to share more details about that today, but essentially that's going to help us I think really optimize our Phase three program. In terms of your question about hepatitis B surface antigen reduction, yes, In the combination of Tabibiravard and Elapsedron and we are seeing three log reduction in Hepatitis B surface antigen, which is much, much greater than our monotherapy with the antibody to Bivibart. Which is a one log reduction. We think this is really important because it shows the potency and the depth of antiviral Vir of our combination therapy it shows that we are as hepatitis B surface antigen is critical for [indiscernible] taken together with both very profound Vir suppression data that we really think we have a very, very good chance of long term viral suppression for patients.

Terms of long term outcomes, I can speculate that because we can achieve such deep and durable suppression of delta virus and HPV surface antigen that we hope that will translate into better outcomes for patients, less progression to cirrhosis, less progression to liver cancer and other poor outcomes. Of course, we have to demonstrate that. But the virus does drive those poor outcomes. So we do think that suppressing those Vir as well as we can with our combination, should lead to better outcomes. Outcomes for patients. So we're very excited about the program and we're moving with all pace to our Phase three This concludes the Q and A session of the call. Thank you for participating and I'll turn the call back over to Marianne DeBacker. Thank you, operator. As we conclude, I'd like to emphasize significant strides that we have made in 2024 and our exciting path forward We've successfully transformed Pierbuy technology into now a dual platform company with promising advancements as you have heard in both infectious diseases and in oncology. Our hepatitis delta program as Mark just mentioned is poised to enter Phase three trial while our innovative T cell engagement platform has shown those really encouraging early results across multiple solid tumor types.

Our strong financial position with a runway extending into mid-twenty twenty seven also provides us with a resources to advance our key programs through critical [indiscernible] So we remain committed to our mission of harnessing the power of the immune system to transform patient's lives and we are more confident than ever in our ability to deliver on this promise. Thank you all for your continued and for joining us today. We look forward to updating you on our progress in the coming months. Operator, you may end the call.

Ladies and gentlemen, that concludes today's call. Thank you all for joining and