VIR - NASDAQ

Hello. Welcome to Vir Biotechnology’s Fourth Quarter and Full Year 2024 Financial Results and Business Update Call. As a reminder, this conference call is being recorded. At this time, all participants are in a listen-only mode. After the speakers presentation, there will be a question-and-answer session. [Operator Instructions] I will now turn the call over to Rich Lepke, Senior Director, Investor Relations. You may begin, Mr. Lepke.

Thank you and good afternoon. With me today are Dr. Marianne De Backer, our Chief Executive Officer; Dr. Mark Eisner, our Chief Medical Officer; Jason O'Byrne, our Chief Financial Officer; and Dr. Mika Derynck, our Executive Vice President of Oncology, will be available during the Q&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-K, 10-Q and 8-K. Please note that any cross-trial comparisons discussed today are not based on head-to-head studies and have inherent limitations and caution should be exercised when interpreting such comparisons. With that, I'll now turn the call over to our CEO, Marianne De Backer.

Thank you Rich and good afternoon everyone. Thank you for joining us for our fourth quarter and full year 2024 earnings call. I'm truly excited to share our progress with you today. 2024 was nothing short of transformative for Vir Biotechnology. 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 Vir 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 to allocate our resources efficiently and make meaningful progress across our pipeline. Now let me start with our infectious disease portfolio. We are moving full steam ahead with preparations for our ECLIPSE Phase III 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 designation 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 delta 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 therapies. Hepatitis delta virus requires hepatitis B surface antigen to complete its life cycle. Our combination therapy of tobevibart and elebsiran offers a unique approach by reducing hepatitis B surface antigen through two distinct and complementary mechanisms. Tobevibart, an Fc-engineered monoclonal antibody is designed to block viral entry and neutralize virions, while elebsiran, a 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 the significant unmet need in chronic hepatitis delta and become a new standard of care. Now turning to our exciting progress in oncology; as many of you know, we held a successful T-cell engager investor event on January 8. The data we presented for VIR-5818, 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, VIR-5500 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 mask construct is being cleaved and activated as intended. These results now across two clinical programs validate the potential of the PRO-XTEN platform to address significant unmet needs in solid metastatic tumors. We are also making great progress with VIR-5525, our EGFR targeted T-cell engager. We are on track to initiate a Phase I study in the first half of this year. Importantly, we have secured worldwide rights to the PRO-XTEN platform in both oncology and infectious diseases. This gives us a powerful foundation for future growth as the platform's universal plug-and-play masking technology can be applied to both existing as well as novel targets. This capability not only supports our current pipeline but also provides us with significant flexibility to expand into additional high-value indications in the future. In hepatitis B, we're looking forward to sharing functional cure 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 a cash runway extending into mid-2027. This solid foundation is the result of our achievements since late 2023, where we significantly reduced our operating expenses and cash burn. We are 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 programs.

Thank you, Jason. This concludes our prepared remarks and we will now start the Q&A section. Please limit your questions to two per person, so we can get to all of our covering analysts. I'll turn it over to you, operator.

[Operator Instructions] The first question comes from Gena Wang from Barclays.

Hi. This is Hang Hu on behalf of Gena Wang from Barclays. So we have two questions. First one is for T-cell engager. So you are using the cleavable linker. 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? And 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?

Thank you very much for that question. I'll ask Mika 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 efficiently 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 PSMA program, both having the double mask and both having the same PRO-XTEN 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 and the absence of prophylactic -- widespread prophylactic corticosteroids, we're really seeing that tumor-specific cleavage. Besides that, the same exact XTEN masking technology is used in an approved drug, ALTUVIIIO, as Mark had mentioned. This drug is a hemophilia drug. It has the same XTEN mask and it uses three thrombin cleavage sites. And it is efficiently cleaved, three sites in the setting of a clot where you have efficient thrombin 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 XTEN masks 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 on the ECLIPSE trial, I will ask Mark to address that.

Sure. Thank you for the question. So we are on track to initiate the ECLIPSE 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 HDV and our very compelling SOLSTICE Phase II 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.

My first question is on the 5525 EGFR TCE program. Can you maybe paint for us a picture of what sort of patients you're envisioning for your Phase I study? Are you going to allow sort of MET treatment experienced patients or patients who have been treated with J&J's RYBREVANT bispecific 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. I realize that the MARCH B data is coming up here next quarter fairly soon. But as 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 sort of 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 and 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 cure data 24 weeks off treatment. We had compelling results at the end of treatment at 48 weeks in the surface antigen low patients with 39% loss in the doublet with tobevibart and elebsiran and 46% loss [ph] in the triplet, including pegylated interferon. In terms of go/no-go criteria, what we said before is we're looking for a 30% functional cure in the triplet, 20% in the doublet, Generally speaking, that's based on our KOL interactions and what could be clinically meaningful. I think it's also may be worth mentioning that [indiscernible] had a 16% functional cure and they're in Phase III based on that. So they -- their Phase III program will read out early next year but that kind of gives you 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 it gives you a little bit of context for what we're looking for.

So I can answer the EGFR question. So this is a pretty standard first-in-human Phase I 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 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 and neck, pancreas and colorectal cancer. But other than that, we're probably going to have patients with a variety of different [indiscernible] treatments.

The next question comes from Mike Ulz from Morgan Stanley.

It's Avi Novick [ph] on the line for Mike. So I guess, number one, on 5525, given the strong safety profile you've seen in the Phase I studies of 5818 and 5500 do you see a read-through to 5525? And do you believe you can possibly more aggressively escalate doses in the upcoming Phase I study? And then my second question is what are you thinking with respect to disclosing data for 5525? Do you think you would maybe plan to do an initial data update as you did for 5818 and 5500 or await for more mature data?

Yes. Thank you for that question. As you know, there have been significant learnings from the HER2 program that were translated the 5500 program and the PSMA program could start at the higher dose and escalate more swiftly compared to the original 5818 program. So we expect that we will continue to learn across the clinical programs and that these learnings will benefit us also as we go into the 5525 program. Anything you want to add here, Mark or Mika?

I mean the only thing is that EGFR is broadly expressed in normal tissue which makes it different from the PSMA program where, of course, there is PSMA expressed outside the prostate. And then the HER2, there is HER2 expressed in lung and heart and other normal tissues but EGFR is broadly expressed. So we're looking forward to this program because it will be a really rigorous 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 Mika alluded to before. But to Marianne's point, yes, I mean, the learnings from the earlier two programs have and will continue to inform 5525 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, the EGFR molecules will use the same PRO-XTEN technology, the same protease linkers, et cetera. But with the HER2 program, we've seen a prior naked HER2 T-cell engager that had a Grade 4 CRS at 0.5 micrograms per kg and IL-6 levels in the 10,000 picomole per ml range, suggesting that there's plenty of normal expression of HER2, enabling that significant CRS. But when you look at our 818 double masked molecule, we -- our start dose was 1 microgram per kg. So higher than this fully unmasked HER2 drug, GBR-1302 that was in the clinic many years ago. So, we do believe with that very wide therapeutic index that we've seen for the HER2 double mask that will give us confidence on the 5825.

The next question comes from Roanna Ruiz from Leerink Partners.

This is Ali Mohammed [ph] on for Roanna Ruiz. But first, so given the early clinical response signals in the heavily pretreated patients, what are your thoughts of potentially moving the T-cell engagers into earlier lines of therapy in future trials? And also, could you elaborate on how machine learning and antibody engineering, your background in that and those capabilities are being applied to optimize the design and efficacy of your T-cell engagers?

Yes. Thank you for that question. As we move into earlier lines, maybe Mark, you can address that.

Sure. So yes, you are correct that in both the HER2 and PSMA programs, the basket trial for HER2, PSMA is all metastatic 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 the 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, I mean, I think one of the beautiful parts about this deal, bringing in the Amunix platform and the people with it is that we can apply our antibody discovery platform and our dAIsY 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 of T-cell engagers. So I think there's a real synergy there between our peers 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 a protein. It could be an antibody, it could be a BiTE [ph] or single or whatever it might be. And then we deploy basically a population 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.

This is Billy [ph] on for Eric. Quick one on the dosing frequency for the EGFR; you've pushed to go to 2, 3 weeks with the other two. Is this something that you continue with the EGFR?

Yes. So we are looking at both Q week and Q3 week for both the HER2 and the PSMA 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 clinical programs are very encouraging and that for the HER2 program appears to be safe and efficacious at both schedules.

The next question comes from Phil Nadeau from TD Cowen.

Two from us. The most common question we currently get on Vir is about the expectations for a dose response for 5500. I'm sure you get that same question. Can you talk a little bit more about what gives you confidence that higher doses will produce deeper, more durable PSA responses given that there wasn't a clear dose response in the initial data? That's the first question. Second question on the timing of the next updates for 5500 and 5818. We appreciate it's too early to give a 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 II dose? Some sense of kind of what you hope to accomplish before giving us the next update would be helpful.

Yes. Thank you, Phil. I mean we are really trying to, as you mentioned right balanced communication of data that is really meaningful with the need to draw important conclusions as to our next steps from the data. And as you know, both programs are in dose escalation. We just discussed, we are exploring two different dosing frequency models. We are exploring in combination with pembro. So a lot of data that needs to read out of safety, efficacy, durability and so on. So as that data develops, we will -- 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 want to address it.

Yes. I think what we tried to emphasize in our investor event in last January is that this is very early in the PSMA program in terms of dose escalation. And we believe we've presented compelling early signs of efficacy in terms of PSMA -- I'm sorry, PSA declines 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 Q week and Q3 weeks and we are anticipating to see deeper and 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 and safety of both the HER2 and PSMA program. So we're really validated, we think, the platform and the masked, dual masked 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 is 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 60 micrograms to 600 micrograms per kilo in that patient, we saw deepening antitumor responses. So that patient is an example of what can happen as we escalate the dose. Now of course, the PSMA program is even earlier and we're continuing to escalate the dose but we anticipate with higher doses, we'll see better efficacy with acceptable safety.

The next question comes from Alec Stranahan from Bank of America.

Just two quick ones from us. First on 5525, apologies if this was already asked but just on the need for steroid prophylaxis, do you think you'd approach this similarly to studies for your other two assets or maybe a different approach just given the breadth of the EGFR expression? And secondly, I appreciate that the additional preclinical mask TC [ph] targets are undisclosed. But I guess as you're approaching maximizing the value of the PRO-XTEN platform in oncology, is your development process driven more by derisked targets or areas of high unmet need maybe with a novel target?

Yes. Thank you, Alex. Maybe I'll address the second question. So since we announced the data on January 8, there 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 PRO-XTEN platform because we do want to make sure we expect that value out of the platform. And again, with promising data across two clinical programs, we think there's a high belief in the potential there. As it relates to the need for prophylactic corticosteroids, just clarifying that we did not use any in our prior program and for 5525, the same is true. I don't know Mark, Mike, anything to add?

Yes. So we've built quite a bit of confidence with this platform with the other two drugs, again, not using -- not having to use prophylactic steroids with really minimal CRS and very minimal IL-6 levels. So for the 5525, we are starting that study without any prophylactic steroids.

The next question comes from Joseph Stringer from Needham.

Financial one from us. Can you just remind us of the details of the collaboration agreement with Alnylam on the elebsiran component? I believe it's a cost profit share but just want to make sure of 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 HBV program?

The next question comes from Patrick Trucchio from H.C. Wainwright.

Just a couple of follow-ups from me on the HDV program. I'm wondering now as more time has passed and you've had more time to kind of digest the data from SOLSTICE if there's been any further learnings 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 in 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 at 24 weeks, 41% of patients reaching complete viral suppression or target not detected at 24 weeks, 64% at 36 weeks and in the 80% range at 60 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 delta, both in terms of the data but importantly, about the demographics of the disease, where the patients reside. And I think those learnings have really informed how we've approach site selection, investigator selection and things of that nature. 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 III program. In terms of your question about hepatitis B surface antigen reduction, yes, in the combination of tobevibart and elebsiran, we are seeing a 3 log reduction in hepatitis B surface antigen which is much, much greater than our monotherapy with the antibody tobevibart which is a 1 log reduction. We think this is really important because it shows the potency and the depth of antiviral effect of our combination therapy. It shows that we are as hepatitis B surface antigen is critical for a delta o life cycle of forming [indiscernible] that this just really taken together with a very profound viral suppression data that we really think we have a very, very good chance of long-term viral suppression for patients. In terms of long-term outcomes, I can speculate that because we can achieve such deep and durable suppression of delta virus and HBV 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 the virus as well as we can with our combination should lead to better outcomes for patients. So, we're very excited about the program and we're moving with all pace to our Phase III initiation.

This concludes the Q&A session of the call. Thank you for participating. And I'll turn the call back over to Marianne De Backer.

Thank you, operator. As we conclude, I'd like to emphasize the significant strides that we have made in 2024 and our exciting path forward. We've successfully transformed Vir Biotechnology 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 III trials, while our innovative T-cell engager platform has shown those really encouraging early results across multiple solid tumor types. Our strong financial position with a runway extending into mid-2027 also provides us with the resources to advance our key programs through critical salient [ph] inflection points. So, we remain committed to our mission of harnessing the power of the immune system to transform patients' lives and we are more confident than ever in our ability to deliver on this promise. Thank you all for your continued support and for joining us today. We look forward to updating you on our progress in the coming months. Operator, you may end the call.