Vir Biotechnology Q4 2024 Earnings Call Transcript

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Provided by Quartr
February 26, 2025

There are 13 speakers on the call.

Operator

Hello. Welcome to Vir Biotechnology's Fourth Quarter and Full Year twenty twenty four 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

To ask a question, you may press star followed by the number one on your telephone keypad. I will now turn the call over to Rich Lepke, Senior Director, Investor Relations. You may begin, Mr. Lepke.

Speaker 1

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

Speaker 1

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 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, Mary Anne DeBacher.

Speaker 2

Thank you, Rich, and good afternoon, everyone. Thank you for joining us for our fourth quarter and full year twenty twenty four earnings call. I'm truly excited to share our progress with you today. 2024 was nothing short of transformative for Veer Biotechnology. As I reflect on the past year, I'm incredibly proud of what we've accomplished.

Speaker 2

We've made significant strides in our oncology and infectious disease program, positioning Virbio 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 three program in hepatitis delta which we expect to initiate in the first half of the year.

Speaker 2

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 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 US where there are no approved therapies.

Speaker 2

Hepatitis delta virus requires hepatitis B surface antigen to complete its life cycle. Our combination therapy of tubevivart and elapsiram offers a unique approach by reducing hepatitis B surface antigen through two distinct and complementary mechanisms. Toberibart, an FC engineered monoclonal antibody, is designed to block viral entry and neutralize virions while elepseram, 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.

Speaker 2

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 year 05/2018 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, FEER 5,500 also showed strong early results in prostate cancer with impressive PSA responses and a favorable safety profile.

Speaker 2

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 Xtend platform to address significant unmet needs in solid metastatic tumors. We are also making great progress with VEER 5,525 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 Pro Xtend platform in both oncology and infectious diseases.

Speaker 2

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 the cash runway expanding into mid twenty twenty seven.

Speaker 2

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 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.

Speaker 2

With that, I'll now turn the call over to Mark to provide an update on our clinical development programs.

Speaker 3

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 CLPS Phase three program in the first half of this year. These studies will form the basis of our marketing applications.

Speaker 3

Before we dive into the CLIPPS program, let me briefly recap our Solstice Phase two data, which 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 viral suppression we can achieve with current testing methods. In our de novo combination therapy arm, at twenty four weeks, forty one percent of patients achieved HDV RNA levels below the target not detected threshold.

Speaker 3

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 or 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 hepatitis B surface antigen levels.

Speaker 3

At week twenty four, approximately ninety percent of participants receiving the combination of tabibibart and lepsiran achieved surface antigen levels below 10 IU per ml. This is a crucial finding because reducing hepatitis B surface antigen is essential for controlling both hepatitis B and hepatitis D virus replication. Additionally, the combination of tibibibar and olefseran demonstrated a favorable safety profile across all 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.

Speaker 3

The EMA has granted us 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 cure 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.

Speaker 3

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 and pure data. Now, let me shift gears to discuss our oncology portfolio to discuss the significant progress we've made with the Pro Xtend platform. As Maryann 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 the ProExtend platform.

Speaker 3

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. The Pro Xtend 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 when in the protease rich tumor microenvironment. The Pro Xtant masks are universal and have been clinically validated as seen in Altuveo, an approved therapy for hemophilia.

Speaker 3

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 VEER 5,818, our HER2 targeted T cell engager. We've seen encouraging efficacy signals across multiple HER2 positive tumors, particularly in colorectal cancer.

Speaker 3

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 HER2 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 a recent investor event, which speaks to the potential for durable responses. A patient with HER2 positive colorectal cancer who progressed through six prior lines of therapy including HER2 targeted agents achieved a partial response.

Speaker 3

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 immunotherapies. This suggests VER5818'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 LONSRF plus befacizumab typically show objective response rates in the single digits. Our early results therefore are particularly encouraging in this heavily pretreated population.

Speaker 3

The safety profile of VERA 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 VERA five thousand eight hundred and eighteen utilizes the pertuzumab binding epitope 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.

Speaker 3

Among the 12 patients treated in the efficacious dose range, one hundred percent experienced PSA declines with fifty eight percent achieving a PSA 50 response and eight percent achieving a PSA 90 response. This is particularly encouraging given the heavily pretreated nature of this population in the early stage of dose escalation. Like VERA five thousand eight hundred and eighteen, VERA five thousand five hundred in early dose escalation has 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 corticosteroid or anti IL-six therapies, which are often required with other T cell engagers, including masked T cell engagers. Importantly, we have not observed any cases of on target off tumor toxicities such as hearing loss, which have been reported with other PSMA targeted therapies.

Speaker 3

We're continuing dose escalation. And based on our favorable safety profile, we believe there's significant room 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, which shows a half life of eight to ten days.

Speaker 3

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 indications 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 strategy.

Speaker 3

Based on our experience with the ProExtend 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 VERA five thousand five hundred and twenty five. Looking ahead, we anticipate sharing additional data from our ongoing dose escalation studies for VERA 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.

Speaker 3

The early data from our T cell engager programs are further validating the potential of the ProExtend 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 and unlocking the full potential of these promising therapies. With that, I'll now hand the call over to Jason.

Speaker 4

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 deprioritized certain programs. Then in September, we executed the agreement with Santa Fe to license three dual mask T cell engagers and the Pro Extend technology.

Speaker 4

While this added modestly to our cost structure, 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 performance. Let me highlight a few key financial metrics for 2024 compared to 2023.

Speaker 4

R and D expenses for 2024 were $5.00 $7,000,000 compared to $580,000,000 in 2023. This decrease was achieved despite absorbing approximately $103,000,000 incentive fee transaction expenses related to our licensing agreement. Excluding this one time transaction related expense, 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.

Speaker 4

As a result, our net loss for 2024 was $522,000,000 compared to $615,000,000 in 2023. Excluding the $103,000,000 Santa Fe 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 2023, 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.

Speaker 4

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-twenty twenty seven. 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: First, we'll accelerate Eclipse clinical enrollment and initiate activities toward registration.

Speaker 4

Second, we'll invest in VER May to rapidly advance the program, capitalizing on the very encouraging PSMA data that was shared in January. Third, we'll continue enrolling patients in VER 05/2018, potentially leveraging the promising early data we see in HER2 positive colorectal cancer. Fourth, we'll initiate the Phase one study for VER5525 in 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.

Speaker 4

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.

Speaker 1

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

Operator

Once you hear the operator announce your name, you can unmute your line and ask your questions. We ask that you please limit your questions to two. Please hold for a moment while we call for questions. The first question comes from Jinah Wang from Barclays. Your line is open.

Speaker 5

Hi, this is Hang Hu on behalf of Jinah Wen 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?

Speaker 5

And how efficient is the cleavage in the tumor macro environment, 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?

Speaker 2

Thank you very much for that question. I'll ask Nikita to address the first one related to the mechanism of action related to cleavage of the liqueurs.

Speaker 6

Yeah. 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 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 is, 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, widespread prophylactic corticosteroids.

Speaker 6

We're really seeing, you know, that tumor specific cleavage. Besides that, the same exact Xtend masking technology is used in an approved drug, Ltuvio's market mentioned. This drug is a hemophilia drug. It has the same Xtend mask and it uses three thrombin cleavage sites, and it is efficiently cleaved, three sites, in the, in the setting of a clot where, you have efficient thrombin activation, efficient cleavage and clotting as needed, as well as not having, clotting, you know, in the state where there is no clotting at 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.

Speaker 6

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.

Speaker 2

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.

Speaker 3

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 HTV and our very compelling Solstice Phase II data.

Speaker 3

So, we're working, quickly to get these studies up and running and we will provide some updated guidance at a future point.

Operator

The next question comes from Paul Choi from Goldman Sachs.

Speaker 7

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 paint for us a picture of what sort of patients you're envisioning for your Phase one study?

Speaker 7

Are you going to allow sort of MET treatment experience patients or patients who have been treated with J and J's RIV event 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, realize that the March V 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? Thank you.

Speaker 2

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

Speaker 3

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 twenty four weeks off treatment. We had compelling results at the end of treatment at 48 in the surface antigen low patients with thirty nine percent, S loss in the doublet with tepibigart and levsiran and forty six percent test loss in the triplet including PEGylated interferon.

Speaker 3

In terms of go, no go criteria, I mean, what we said before is we're looking for a thirty percent, 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. I think it's also maybe worth mentioning that, GSK's Doctor. Rogerson had a sixteen percent functional cure and they're in Phase three based on that. So they, you know, their Phase three program will read out early next year.

Speaker 3

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 it gives you a little bit of context for what we're looking for.

Speaker 6

So, I can answer the, EGFR question. So, this is a pretty standard first in human Phase one study, and in such that, we patients must have exhausted all current standard of care, to be enrolled on study, which means that they must have exhausted, you know, 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 and neck, pancreas and, colorectal cancer. But other than that, we're probably going to have patients with a variety of different prior treatments.

Operator

The next question comes from Mike Ulz from Morgan Stanley. Your line is open.

Speaker 8

Hey, it's Avi Novak on the line for Mike. Thank you for taking our questions. So I guess number one on 5,525, given the strong safety profile you've seen in the Phase one studies of 05/2018 and five thousand five hundred, do you see 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?

Speaker 8

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.

Speaker 2

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, you know, the PSMA program could start at the higher dose and escalate more swiftly compared to the original 5,818 program. So we expect that we will continue to learn across the clinical programs and that these learning will benefit us also as we go into the five five to five program. Anything you want to add, Mark or Lisa?

Speaker 3

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 in the HER2, there is HER2 expressed in lung and heart and other normal tissues. The eGFR 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 Mika alluded to before. But to Mary Anne's point, yes.

Speaker 3

I mean, the learnings from the earlier two programs have and will continue to inform 05/2025 and further programs. So we do expect, to be efficient in how we conduct that.

Speaker 6

Yeah. And I might just also add in that, you know, from the HER2 program, again, EGFR molecules will use the same ProExtend technology, the same protease, Langer, etcetera. With the HER2 program, you know, we've seen a prior naked T cell, HER2 T cell engager that had a grade four CRS at 0.5, and IL-six levels in the 10,000 range, suggesting that there's plenty of normal expression of HER2 enabling that significant CRS. But when you look at our eight eighteen mass double mass molecule, we, our start dose was one microgram per kg, so higher than this, the fully unmasked HER2 drug GBR thirteen oh two 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 this HER2 double mask that that will have give us confidence on the 05/2025.

Operator

The next question comes from Rowan Ruiz from Leerink Partners. Your line is open.

Speaker 9

Hi, this is Maysi Ali Muhammad on for Rouan Ruiz. 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 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 design and efficacy of your T cell engagers?

Speaker 2

Yes. Thank you for that question. As to moving to earlier slides, maybe Mark can address that.

Speaker 3

Sure. So, yes, you are correct that in both the, HER2 and PSMA programs, you know, 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.

Speaker 3

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. I 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 platform and 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 of T cell engagers.

Speaker 3

So, I think there's a real synergy there between our VIIRS antibody discovery and optimization platform that's AI driven and the T cell engager platform that we now have in house.

Speaker 2

Yeah, I would just add that, you know, our protein engineering platform is really such that, you know, we start with a starting point of a protein. It could be an antibody, it could be a bite or, you know, a single chain or whatever it might be. And then we deploy, basically a compilation of different models to come up with molecules that have increased characteristics, you know, better potency, you know, 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, you know, an output that we can quickly test in biological models and that sort of feeds back into the database.

Operator

The next question comes from Eric Joseph from JPMorgan. Your line is open.

Speaker 8

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 two, three weeks with the other two. Is this something that you continue with the eGFR?

Speaker 6

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.

Speaker 8

Great. Thanks for taking my question.

Operator

The next question comes from Phil Nadeau from TD Cowen. Your line is open.

Speaker 10

Good afternoon. Thanks for taking our questions. Two from us. The most common question we currently get on VIR is about the expectations for dose response for five thousand five hundred. I'm sure you get that same question.

Speaker 10

Can you talk a little bit more about what gives you confidence that higher doses will produce deeper and 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 May and 05/2018, 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?

Speaker 10

Some sense of kind of what you hope to accomplish before giving us the next update would be helpful. Thank you.

Speaker 2

Yes. Thank you, Phil. I mean, we are really trying to as you mentioned, balance communication of data that is really meaningful with, you know, 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're exploring two different dosing frequency models.

Speaker 2

We are exploring combination with pembrode. So a lot of data that needs to read out on safety, efficacy, durability and so on. So as that data develops, you know, 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, if you want to address it.

Speaker 3

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, PSAA 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 Q3 and Q3 weeks.

Speaker 3

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 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 start deepening anti tumor responses. So that patient's an example of what can happen as we escalate the dose.

Speaker 3

Now, of course, the PSMA program is even earlier and we, we're continuing to escalate the dose. But we anticipate with higher doses, we'll see better efficacy with acceptable safety.

Operator

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

Speaker 11

Hey guys, thanks for taking our questions. Just two quick ones from us. First on 05/2025, 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, appreciate the additional preclinical, mass 2c targets are undisclosed. But I guess as you're approaching maximizing the value of the ProExtend platform in oncology, is your development process driven more by derisked targets or areas of high unmet need, maybe with the novel target?

Speaker 11

Thank you.

Speaker 2

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, you know, getting educated on what some potential partners might be interested in.

Speaker 2

So, you know, we will certainly share, going forward some more insight into how we're thinking about what next preclinical programs could be that really take advantage of the ProxNet platform because we do want to make sure we extract 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, in our drive program and for 05/2025, the same is true. I don't know, Mark, you got anything to add?

Speaker 6

Yeah. 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, very minimal IL-six levels. So,

Speaker 2

for the 05/2025,

Speaker 6

we are starting that study without any prophylactic steroids.

Operator

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

Speaker 12

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, the Lev Saran component? I believe it's a cost profit share, but just want to make sure of the details on the cost share.

Speaker 12

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? Thank you.

Speaker 2

Yeah. Thank you for that question. So our collaboration agreement with Alnylam spanning from 2017 is a pure financial arrangement. So there's no operational role that Alnylam is playing in the development nor the commercialization. Alnylam does have an option to either, you know, step into the program and share 50% of the cost as it relates to the elapse run component of the regimen and then of course also share, you know the commensurate percentage of the profit or opt out and have a typical type of milestone and royalty deal.

Speaker 2

So that is an option that Alnylam still needs to decide on. You know, the impact of any partnership related to HBV, you know, both are possible. I mean, again, because the nature of the deal with Alnylam 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 commercialization. Obviously, it would be easier if there was sort of one, one partner for the program that's both are possible.

Speaker 4

Could I just add, yeah, on this, further details will be in the 10 ks on the island agreements. And just as you think about our runway, we have, sort of assumed the worst case in the shorter term, which is, that Alnylam opts out, in the shorter term if they opt in and and do a profit share that would potentially be upside.

Operator

The next question comes from Patrick Trucchio from H. C. W. W. Baird.

Operator

Your line is open.

Speaker 3

Thanks. Good afternoon. Just a couple of follow ups for 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 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 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?

Speaker 3

Yeah. Thanks, for the question. So, in terms of Solstice, just to recap for everyone, I mean, we did see a twenty four weeks, forty one percent of patients reaching complete viral suppression are targeted not detected at twenty four weeks, sixty four percent at thirty six weeks, and in the eighty percent range, at sixty weeks in the rollover cohort. So, I think we're really seeing, you know, 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.

Speaker 3

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, approached site selection, investigator selection, and things of that nature. So, you know, 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.

Speaker 3

In the combination of tabibigard and elopiram, we are seeing a three log reduction in hepatitis B surface antigen, which is much, much greater than our monotherapy with the antibody tepigovart, which is a one 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 because hepatitis B surface antigen is critical for delta lifecycle and forming nevirion, that this just really, you know, taken together with the 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 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.

Speaker 3

But the virus does drive those poor outcomes. So, we do think that suppressing those virus, 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 three initiation.

Operator

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.

Speaker 2

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 Seer 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 three 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 twenty twenty seven also provides us with the resources to advance our key programs through critical value and infection points.

Speaker 2

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.

Operator

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

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Earnings Conference Call
Vir Biotechnology Q4 2024
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