Q3 2025 Arvinas Inc Earnings Call
Speaker #1: Thank you for standing by and welcome to ARVINAS, INC. Third Quarter 2020 Earnings Call . I'd like to remind everyone that this call is being recorded and that all lines have been placed on mute to prevent any background noise .
Speaker #1: After the speakers remarks , there will be a question and answer session . If you would like to ask a question during this time , simply press star , followed by the number one on your telephone keypad .
Speaker #1: If you would like to withdraw your question , press star one . Again , thank you . I would now like to turn the call over to Mr. Jeff Boyle .
Speaker #1: You may begin .
Speaker #2: Good morning , everyone , and thank you for joining us . Earlier today , we issued a press release with our third quarter 2020 financial results , which is available in the investor and Media section of our website at tennis.com .
Speaker #2: Joining the call today are John Houston , our Chief Executive Officer , president and Chairperson Noah Berkowitz . Our Chief Medical Officer , Angela Cacace .
Speaker #2: Our Chief Scientific Officer and Andrew Saik , our Chief Financial Officer . Before we begin the call , I'll remind you that today's discussion contains forward looking statements that involve risks , uncertainties and assumptions which are outlined in today's press release and in the company's recent filings with the US Securities and Exchange Commission , which I urge you to read .
Speaker #2: Our actual results may differ materially from what is discussed on today's call . A replay of today's call , as well as an updated corporate deck , will be available in the Investor and Media section of our website .
Speaker #2: And now I'll turn the call over to John . John .
Speaker #3: Thanks , Jeff . Good morning , everyone , and thank you for joining us today . As highlighted in our third quarter earnings release issued earlier this morning , this has been a dynamic and productive period for our business , marked by meaningful progress across both our corporate initiatives and clinical development programs .
Speaker #3: During the quarter , we announced significant developments both in our pipeline and enhancing efficiency across our organization . All here that driving value from our portfolio to deliver benefit to patients and value to shareholders .
Speaker #3: Our deep pipeline provides multiple opportunities for value creation as we work to address the largest areas of significant unmet need in oncology and neurology .
Speaker #3: We have entered the beginning of a data rich period with multiple readouts from our early stage clinical programs , including recent clinical data from IRB 102 or Lrrk2 , Degrader and preclinical data from ARV 806 .
Speaker #3: Our Kras G12d Degrader . We also presented the first preclinical data from ARV 027 . Our promising new clinical candidate that targets Polyglutamine expanded androgen receptor or AR .
Speaker #3: The root cause of spinal bulbar muscular atrophy or sbma . In addition , we also anticipate sharing preclinical data from our bcl6 degrader ARV 303 at the Ash conference in December and pre-clinical data from our new Hpk1 Degrader ARV 6723 later this week at the conference .
Speaker #3: Noah will also share a promising update from our ongoing phase one monotherapy trial with ARV 303 . Later in the call today , we have a strong track record of translating promising preclinical results into important successes in the clinic with a platform that has consistently shown its versatility and promise .
Speaker #3: We continue to build on that record with multiple ongoing and planned clinical trials in areas of high unmet need , a pipeline of high value assets , a strong research engine , and cash on hand into the second half of 2028 .
Speaker #3: That gives us financial and strategic flexibility . In September , we announced that we and Pfizer will jointly select a third party for the commercialization and potential further development of Dagestan , with the goal of rapidly bringing it to patients if approved , new drug Application is currently under review by the FDA and the agency has issued a adufa action date of June 5th , 2026 .
Speaker #3: Our goal is to have a partner in place before this date to ensure that vet deg , if approved , is launch ready as a potentially best in class therapeutic option for er positive , Her2 negative advanced breast cancer .
Speaker #3: In the second line , ESL one mutant setting of ARV 393 . Noah .
Speaker #4: Thanks , John and good morning everyone . I'll begin with ARV 102 . Our oral protocol degrader specifically designed to be brain penetrant .
Speaker #4: Enthusiasm from key opinion leaders and investigators, most recently regarding the biomarker data we presented at MDS, has further strengthened our belief that this is a truly differentiated program.
Speaker #4: Let me begin with some background about ARV 102 target and what has come into focus as potential diseases of interest . Morc2 is a multi-domain protein with three key functions of kinase , GTPase and scaffolding activities .
Speaker #4: These activities help it regulate endolysosomal trafficking . When Lrrk2 expression or activity is elevated , it disrupts lysosomal function , impairing the clearance of aggregated pathologic proteins that would normally be degraded through the pathway degrading Lrrk2 may restore and lysosomal homeostasis and provide therapeutic benefit in disorders characterized by lysosomal dysfunction .
Speaker #4: Unlike inhibitors that only inhibit Lrrk2 kinase activity , intermittently , ARV 102 eliminates the entire Lrrk2 protein . This is important because the three key functions , not just kinase activity , may be linked to neuroinflammation and lysosome dysfunction .
Speaker #4: Increased activity , scaffolding , and expression of Lrrk2 have been implicated in the pathogenesis of neurological diseases , including idiopathic Parkinson's disease , a prevalent neurodegenerative disease , and progressive supranuclear palsy or PSP , a rapidly progressing neurodegenerative disease that is typically fatal within 5 to 7 years of diagnosis .
Speaker #4: We believe that eliminating all three functions of Lrrk2 through Protac mediated degradation offers the potential for deeper and more durable therapeutic benefits versus traditional inhibitors .
Speaker #4: At the MDS conference last month , we were pleased to share data from two ongoing phase one clinical trials with RB 102 , one in healthy volunteers and one in patients with Parkinson's disease .
Speaker #4: Both trials included single , ascending and multiple dose portions . ARV 102 is generally well tolerated in both trials . In the healthy Volunteer Study .
Speaker #4: ARV 102 was well tolerated at single doses . Up to 200mg and multiple daily doses up to 80mg , with no discontinuations due to adverse events or serious adverse events observed in the study .
Speaker #4: Population . In the Parkinson's Disease Study , single doses of ARV 102 at 50mg or 200mg were well tolerated , with only mild treatment related adverse events which were generally lumbar puncture procedure related and with no serious adverse events .
Speaker #4: Pharmacokinetic data were also excellent across both trials . ARV 102 demonstrated dose dependent PK in both periphery and the CSF . The latter indicating brain penetration in terms of pharmacodynamic effects .
Speaker #4: In healthy volunteers repeated daily dosing of ARV 102 led to lrrk2 reductions of up to 90% in peripheral blood mononuclear cells , or pbmc , and more than 50% in the CSF .
Speaker #4: Repeated daily doses of ARV 102 resulted in reduced concentrations of phospho rab10 , t73 and PBMCs , and urine concentrations of BMP . Both of these are important biomarkers for modulation of the lysosomal pathway downstream of Lrrk2 .
Speaker #4: In patients with Parkinson's . We showed that single doses of ARV 102 resulted in median pbmc lrrk2 protein reductions of 86% , with the 50mg dose and 97% with the 200mg dose dose .
Speaker #4: Perhaps most interestingly of all , in healthy volunteers treated with 80mg of ARV 102 once daily for 14 days , unbiased proteomic analysis of CSF showed decreases in many lysosomal pathway markers , such as gpnmb and Neuroinflammatory .
Speaker #4: Microglial markers like Cd68 . A recently published proteomics analysis showed the same panel of biomarkers was elevated in patients with lrrk2 related Parkinson's disease .
Speaker #4: We are aware of inhibitor data showing the movement of some of these biomarkers , but only in patients with Parkinson's disease and only after at least a month of treatment to engage the intended disease pathway .
Cd20 expression, we intend to initiate a combination trial with Gloom next year and look forward to updating you on our progress.
Turning to our clinical progress to date enrollments in our Phase 1 monotherapy trial is ongoing. This is a first in human dose escalation trial and we have not yet achieved the predicted efficacious, exposure level. However this morning, I'm pleased to report that even an exposure levels below. Those predicted to be efficacious, we have already seen responses in early cohorts in both B and T Cell lymphomas. We also see evidence of robust bcl6 segregation and the safety profile of arv 393 has supported continued dose escalation. We are very pleased with these early data which we believe support in emerging and differentiated therapeutic benefits of arv. 393 we look forward to sharing additional data from The Phase 1 trial at a medical Congress in 2026 with that. I'll now turn the call over to Angela Angela.
Thanks, Noah, and good morning everyone. I'm pleased to share compelling preclinical data. We recently presented that reinforces our confidence in our ability to deliver differentiated treatments across our oncology and Neuroscience pipeline. I'll begin with arv 806 our
Novel protest a greater targeting kras g12d.
Kras. G12v is a well characterized conco driver associated with poor prognosis and recalcitrant, to standard treatments across several major tumor types, including pancreatic colorectal, and non small cell lung cancers. There are currently no approved targeted therapies for kras g12d.
At the triple meeting and October we share preclinical data, highlighting, the high potency of arv 806 and it's clear differentiation from both kras Inhibitors and degraders. Currently in the clinic.
These pre-clinical data showed dose dependent robust anti-tumor activity. With regression of across pre-clinical models of kras, g12d mutant cancer, arv 806 reforms productive, ternary complexes with the on and off states of kras g12d, demonstrated in, vitro Peak, Amar potency with near complete degradation and high selectivity.
Arv 806 demonstrates, anti-proliferative activity, approximately 25 times greater than kras Inhibitors and the leading clinical stage degrader.
Importantly arv 806 induces durable, degradation greater than 90% for 7 days after a single dose with efficacy across pancreatic colorectal and lung cancer models.
We also presented early and very promising preclinical data from our oral Paneras degrader and look forward to sharing more as this program advances.
We are rapidly enrolling, a phase 1, clinical trial of ARB 806 reflecting strong interests from Clinical investigators and underscoring. The high unmet need for Effective KRA targeted therapies. We look forward to sharing initial clinical data from this trial next year.
finally, I'd like to briefly mention updates from 2 other promising programs that you'll hear more about in 2026,
First at World muscle in October, we shared exciting, preclinical data for arz 027, a protactic grader designed to Target polyglutamine, expanded Androgen receptor or polyq are and skeletal muscle.
This degrader will be developed for patients with spinal and bulbar muscular atrophy, or SBMA, a rare genetically defined neuromuscular disease with no approved treatments and significant unmet need.
Second this week at 50, we will introduce our first immuno-oncology focused protector greater arv 6723.
Immune suppression and could be relevant for numerous solid tumors.
Our preclinical work to date suggests that degrading Hpk1 leads to differentiated biology versus Hpk1 inhibitors and anti-PD-1 therapies.
We anticipate beginning first-in-human studies for ARV-027 and ARV-6723 in 2026.
As we begin, those studies, we look forward to providing full updates on the unmet need for each disease. The rationale for each high impact targets and why we believe that our protactic graders will represent highly differentiated therapies for patients with that. I'll turn the call over to Andrew to review our quarterly financial information.
Thank you, Angela, and good morning, everyone. I'm pleased to provide financial highlights for the third quarter ended September 30, 2025, and to expand on our approach to capital allocation.
Capital returns and development strategy.
As a reminder, detailed Financial results for the third quarter are included in the press release, we shared this morning.
I'll begin by briefly touching on some key financial highlights for the third quarter of 2025.
At the end of the third quarter, we had approximately 787.6 million in cash, cash equivalents and marketable, securities on the balance sheet compared with 1.04 billion, as of December, 31st 2024,
Revenue for the 3 months and in September 30th, 2025 total of 41.9 million compared to 102.4 million. For the 3 months, ended September 30th 2024
The decrease of 60.5 million was driven by the Novartis license agreement which was entered into during the second quarter of 2024 with Revenue recognized through the end of 2024 offset by the recognition of a milestone payment from novardis of 20 million this quarter as part of the same agreement.
General administrative. Expenses were 21 million in the third quarter compared to 75.8% of 2024. The decrease of 54.8 million was primarily due to a decrease of 43.4 million from the termination of our lease of 101 College Street in August. 2024 a decrease in personnel and infrastructure related costs of 7.3 million
And professional fees of 3.6 million.
Total non-gaap GNA for the quarter was 14.6 Million compared with 64.8 million in the prior year.
Research and development. Expenses were 64.7 million in the third quarter compared to 86.9 million for the same period of 2024.
The decrease of 22.2 million was primarily driven by a decrease in the Zep deg program of 5.4 million, a decrease in the Luxe, egg program of 4.7 million and the decrease in Personnel, expenses and non-programmed specific expenses of 15.1 million offset by an increase in the kraz program of 4.3 million.
Total non-gaap R&D, for the quarter was 56.9 Million compared to 73.2 million in the prior quarter.
Total non-gaap expenses were 71.5 million in the quarter. We expected expenses to continue to decline as we work with fiser to ramp down our spend on, zepe. And as our cost reduction programs, take full effect
Our goal is to continue with the quarterly run rate, spend below 75 million, which will allow us to manage non-gaap expenses below $300 million in fiscal year 2026.
In September, we announced that our board had authorized the repurchase of up to $100 million of our outstanding common stock.
This authorization, underscores the board's confidence in our long-term strategy and its beliefs that our current share price is undervalued relative to our long-term opportunity.
As of the end of September, we have bought back approximately 2.56 million shares at an average share price of $7.91 per share.
Details of our stock repurchase program can be found on our 10 Q.
At the same time we announced further cost reductions that allowed us to maintain our prior cash Runway guidance into the second half of 2028.
We we remain committed to investing in areas that will maximize shareholder value as we move towards important catalysts in the coming months.
Can you look at ways to reduce costs and increase efficiency while continuing to focus on our goal of progressing? Our very promising early pipeline.
With that, I'll turn the call over to John for closing remarks. John
Thanks Andrew. We are focused on continuing to deliver Innovative and differentiated access in areas of high unmet need.
We are operating with scientific rigor and building on our proven contractors of success from Discovery to clinical to collaborations.
We have a deep Pipeline with multiple clinical candidates for near Mid and long-term value creation. And the potential be to be differentiated with critically important therapies for patients.
our Venice is entering a pivotal phase and is drove to dentry our clinical pipeline offers a rich set of catalysts throughout the balance of the year and into 2026 with multiple study initiations and data readouts anticipated across a neuroscience and inkology franchises
With our pedophile date. Now confirmed for next year, we are approaching an historic moment with the potential for the first ever approval of a protonic therapy.
We are well positioned to deliver significant value for our shareholders, our partners. And for the patients, we serve
With that, I'll send the call over to Jan, to begin the Q&A portion of the call Jeff.
Before I turn the call over to the operator, I'm going to ask that you limit yourself to one question per cycle to make sure we're able to give everyone the appropriate time. You can feel free to join the queue afterward for a follow-up question. Uh, so with that, operator, can you please open up the queue?
Thank you. We will now begin the question and answer session if you have dialed in and would like to ask a question. Please press star 1 on your telephone keypad to raise your hand and join the queue. If you would like to withdraw your questions simply press star 1 again, thank you. Your first question comes from the line of absurd to road with parkleigh. Your line is now open.
Great. Uh, thanks for taking the question, just a quick question on. Um, uh, the um, V6 to Greater program just and we're going to see some updated data from bullet Ash. I just wanted to, if you could comment on points of differentiation there that they're doing a little bit about the dosing profile that that you envision for the model in any areas you could potentially differentiate longer term molecules. Thank you.
Great. Thank you so much for the question and uh, yeah, we're very excited about our bcl6 program and we do believe that we have a profile that will differentiate itself. Um, as the the compound continues to be developed
No. Do you want to add some comments? Sure. Thanks, John. Thanks for the question. Uh, yes. So indeed we and by the way, you broke up a little bit but uh, if it had to do with dosing so differentiation and differentiation. So the the drug is being dosed once daily in oral drugs. Um, differentiation has to do their on a couple of different levels. Number 1 is that um, we've already demonstrated and we'll continue to demonstrate uh upcoming it, Ash some uh, kind of uh I guess the differentiated profile for combinations of the drug and even from monotherapy preclinical. So we noticed that we can achieve uh complete responses and various models versus tumor growth. Inhibitions uh, that are seen with some competitor, uh, or yet some competitor. Uh drugs. Um, in terms of our program, we're focused.
In mono we've said pretty explicitly that we're focused in mono therapy for aitl and we're interested in developing the combination with the by specific uh for dlbcl. So uh there's there at this point several competitors that have entered the market uh 1 a little, you know, 1 of them that has already reported data, the others seem to have just filed their IND. Um, we believe that, uh, and we've shared data here that we have monotherapy activity and T cell, and B cells that has not been reported uh by um the competitor that's already reported out some uh be some malignancy responses um and and so that's a point of potential differentiation in the future.
Great. Thank you, thank you. Yeah.
Your next question comes from the line of ego.
Your line is now open.
Is Caroline on Fugal, thanks for kicking a question.
On your larq 2 program. Can you tell us about the first types of signals, you'd be looking for in the Parkinson's disease map? Phase 1
And how long do you hypothesize? You'll need to dose for the PK effects that you've already observed in healthy Volunteers. In Parkinson's, patients to translate to clinical clinical benefits
Thanks.
Great question.
Uh, thank you for the question. So yeah. We're pretty excited about what we've seen so far with our L2 degrader, and the reception that we received at a recent conference in MDS. Um, so as you state, we are currently moving pretty aggressively through a Parkinson's disease, Phase 1 study, that has 28 days of dosing. Uh, we expect that this will generate, uh, data that's principally biomarker related, um, and uh, but we may also start to collect a little, uh, clinical efficacy data. That that's not expected with 28 days. Dosing, now what we've shared is that we've already been able to demonstrate pathway engagement in ways that competitor competitor Lark to Inhibitors have been had at least have not reported today. So we know in healthy volunteers we can impact endolysosomal
Trafficking and also um neuroinflammation at least uh through micro gal, um, Pathways mediated Pathways. And so now, when we look at our Parkinson's disease patients, the idea would be we have patients at Baseline who have more than 2 maybe even 3 times the Baseline level of Lark 2 in their CSF. There's much more activation of these Pathways. And it will be important to see how much what, uh, the degradation that we've already reported out in healthy volunteers. We can recapitulate now in this Parkinson's disease population and look at that pathway engagement. So we've guided to an update on those pathway markers. Um, or you know, next year relatively early next year and um you know, but I think that the next step for clinical data will be when we can have more than 28 days of treatment. So
For that. We're working our way through, uh, The Chronic tox study. And so you'll see as we file our IND next year, that allows us to move into PSP that we're prepared to continue with chronic treatment of patients and that will be an opportunity for us to uh to demonstrate the clinical benefits um, in diseases like PSP and potentially Parkinson's.
Thanks Noah. Thank you.
Your next question comes from the line of Michael Schmidt with gimme. Your line is now open.
Hi. This is Sarah, I'm from Michael. Thanks so much for taking my question. Um I just wanted to ask on your cos g12d. Uh so you've mentioned before and we've seen evidence for, um, cos amplification, uh, as a mechanism of resistance to Inhibitors. So, uh, and uh, the fact that potentially with the iterative activity of a protest, um, might be able to overcome that. Um, so just wanted to ask if you have any plans to potentially test 806, uh, or maybe even eventually your Paneras in the clinic and I could ask Amplified population.
Yeah, great questions here. Um, I'm going to ask both um, Angela kcrc so and know what to to give you 2 parts to uh, to that answer. Great, thank you for the question, we have been studying, um, certainly our g12d to Greater arv 806 in resistance setting and um, you know, we look after we see amplification of kras g12d and we see that we durably repress
Um, hey Ross and all conditions. And then for our um,
So Sarah do your question about um amplification and what we've seen. So we specifically right in the ongoing Phase 1 Study, we exclude patients that have been treated previously with cos inhibitors.
So, um, that's not something we're going to see in the dose escalation portion of our study and you would understand why we would uh want the cleanest signal. We've uh, made that choice. Um, as really anyone would. Um, but we have, we have learned over the past over the past year. Uh, and this is really data that's generated outside of our company. Write that as data. You know, we see many reports of amplification being a principal mechanism of resistance, uh, after patients have been exposed to to kras Inhibitors. So we've obviously as Angela's pointed to, we've done work in our models to show that uh, that this creates a great opportunity for us moving forward.
And, you know, expect some updates over the course of the next year. In terms of, if we want to expand our, uh, targeting or thinking, in this regard, it certainly is compelling science.
Thanks both. Thanks so much.
Your next question comes from the line of Derek archila with Wells Fargo, your line is now open.
Good morning. And this is how calling in for Derek. Um, from Wells Fargo. Um, thank you so much for your question. Um, so I just, uh, we have questioned on the arv while too, um, for the
For the Set. Uh data. Do you see any CSF degradation for log 2? And uh, um, then for the M data next year in 2026 just wonder to see. Do you have any expectations? Um, is the fifth more than 50% in healthy volunteer? You wanted to repeat or um you know, just some expectations for us to set up. Thank you so much.
So, thanks for the question. Um, absolutely. So um, no I asked do you want to take that? Yes. So but I think we've guided to this, uh, essentially, we will provide our Lark to degradation data when we've, uh, completed the Mad in the Parkinson's disease patients. And um, that's
That's basically what we're going to guide to for next year.
Thank you.
Sure.
Your next question comes from the line of Egypt with btig, your line is now open.
Great, thanks for taking my question. Um, just coming back to arv 806 based on your learnings from other g12d Inhibitors and degraders. And development, are there any molecular features or attributes that may be correlated to, or linked to the GI tolerability and elevated liver enzymes. We've seen with some of these molecules and if yes, does 806 avoid those features? Thanks.
Yeah, thanks for the uh, the question. Um,
I mean, and I think certainly the um our g20d component, has a very um um, exciting profile. Um, obviously the molecule is different from other g2d Inhibitors. Um, maybe Angela you want to talk to what you think might be? Some of the kind of the features that, um, give the profile that we see. Sure. So as we described our arv 806 g12d protac, um, really does have some very nice features, from a molecular perspective, it binds to both the on and the off State and is 25 times more potent than all. All mechanisms that are currently in the clinic that we've tested to date. Um, the
You know, given what we've seen with the clinical degrader. We're also, um, several orders of magnitude more potent had engaging, the Target and um
Is that was seen. So the fact that we can engage our Target at uh much lower uh a much lower concentrations, you know, suggest that we have the potential not to run into those types of toxicities and still get the significant degradation, we're shooting for. So we're looking for more than 80% degradation of our Target. We could probably do, you know, significantly better than that and um, you know, we'll provide updates as we go through our dose escalation cohorts.
Your next question comes from the line of Sudan loganathan with Stevens, Inc. Your line is now open.
Hey, good morning our business team. This is uh, kov on behalf of Sudan. Uh, got a quick 1 on 8006. Are you all evaluating how Protek and media medicated uh crash? Uh, g12 degradation might complement or differ from combination strategies? Like the tuck, tuck some add pairing seen with the various stems. Uh, crash, 12 a g12 inhibitor. Thanks.
Yes, so preclin. Um, we have evaluated, um, combination with anti-egfr, um, Inhibitors, like socks. And so, we think this is a, a big Advantage because we have a selective approach to degrading g12d KRA. Um, we combine very well in that case and we'll be sharing the pre-clinical data that we've generated, um, in those combinations. Um,
Within the year, right? And um, yeah, we just add that. Um, there's certainly are accumulating evidence that combinations of Inhibitors with chemotherapy but also, as you mentioned, within egfr, inhibitor can lead to uh, cumulative talks, you know, which may be limiting for this drug but creates the for this, uh, set of inhibitor Inhibitors, but that creates an opportunity for us, especially right. Because going back to this potency argument. If we can get our drug on board which right now uh requires weekly dose, once a week dosing and may allow us eventually to also get to once every 2 week dosing, and we can do this with uh lower uh dosing uh um lower Doses. And we might not achieve the
same type of, uh, uh,
Talks from, uh, from a combination that opens up a whole set of opportunities, to generate the better benefit risk profile. So, you know, again where we have to get through our monotherapy dosing, it's moving very fast. Uh, and we, you know, it, we're hoping that we can get into our combinations next year already, but, uh, more to follow on that and just to briefly add that, you know, tackling. Um, you know, the tan wrap mechanism is a challenge and that combination setting largely because they're also hitting n in hrf and that becomes a big challenge, um, for um, adding on and egfr based mechanism.
So our, our brows g12d to Greater would avoid that.
Your next question comes from the line.
Of Tyler. Van Burren. The TD security is your line is now open.
Good morning. This is Francis on for Tyler. Thanks for taking my question. So, for the bcl6 asset, what combination Partners do you believe are most exciting and where do you think it's most likely to exist in the lymphoma treatment? Par Paradigm, if successfully developed
And also, uh, anti-cd20 agents. So those, you know, that's the whole set of opportunities for combination, we recognize that the EV the way the field is evolving. There's a um, there's going to be a significant outsized role for by specifics targeting cd20 in the eventually the first line setting. But in the second and third line setting as well for, uh, for large piece cell lymphoma, we think that's our, you know, we want to be laser focused as a company and we recognize that's a significant opportunity where we can combine these uh these therapies that have non overlapping toxicities, you know, ours we first have to identify a toxicity. Um but but obviously there is CRS with the by specifics and um and we should be able to combine favorably.
With those and that would be our plan. That's why we've announced that. Uh, next year, we expect to be moving ahead in our, um, you know, our Phase, 1 study with uh, with combinations. With by specifics,
Your next question comes from the line of the WhatsApp with Contour Pizza. Uh, pizza roll. Your line is now open.
Hey good morning guys um a strategy question from me. Um it looks like you're moving you know more programming into the prequel clinical settings. Um and then maybe deepening your Footprints in your muscular um space and expanding into IO. So you know just curious number 1, your baby's strategy here um given that you got you know, 5 programs and then 2 your approach to um resource allocation.
Yeah, so thanks. Thanks for the question. Yeah, clearly. Um,
the last several months, uh, the the company has done a significant reset. Um, obviously with um, the uh, decision along with fisa to, um, find a new partner or out license, but they just trying to load us to focus on the rest of our pipeline. Um, and obviously care sg12, D, log 2,
And dl6 are are next. In line assets that are in Phase. 1 heading, fully rapidly to phase 2. And then we have 2 Programs, uh, behind that. That we should be in the clinic relatively soon. Uh, 1 in, um, sbma, which we can talk to and the other hpk1, which is an IO. And we believe,
Believe that gives us an array of different uh programs across oncology and neural and yes hpe1000.
Give us a lot of flexibility. Gives us a lot of choices and as ever and the history of the whole history of our Venice.
Those choices have also included, um, appropriate and um, well, placed BD opportunities, so we'll always be open for that. Um, we think that some of our targets that really lend themselves to, uh, be the opportunities. Um, and uh, right now, um, as we stand today, all of our portfolios fully owned by our our our V, and we did do a great deal with nartis on much like lumite. So yeah, we move forward with a lot of confidence and we have some really great exciting data. That should be uh coming out over the next uh several months and a year and uh we'll be able to position our portfolio is the best way we can and that can that could include the selective partnering.
Your next question comes from the line of care. But deara condo with tourist Airline is now open.
Thank you so much for taking my question guys. Um, maybe a follow-up question to the previous 1 know, with nearly 800 million, um, in cash and Runway to second half of 28, not just in terms of the timeline, um, the, the runway timeline, but in terms of what studies you can get through with this cache would be helpful. And also, as you are advancing your pipeline, you continue to, uh, do you expect to continue protects in both oncology and CNS or at this point of time? Do you think there is a need to prioritize from a therapeutic area perspective? Thank you.
Thanks for the question. I I'll send the hand over to our CFO Andrew to, to talk about the first half of that question. But in terms of the balance, yeah, we've the company break from this beginning has been an oncology company and and uh,
Getting Neuroscience right from the beginning of the company's Inception.
And we think protacs and the ability to get uh brain penetration protects gives us a huge potential advantage in neuro degenerative diseases. So we want to explore that as we go forward with our programs. Uh, like Lot 2 will also be. Now be very excited to be looking at neuromuscular Target like sbma.
And we do still think we've got a lot of differentiation in the oncology space, so a lot a lot. Me sound, like, uh, 2, um, very radically different therapeutic areas, uh, the insights, and the ability to use protacs in those areas really does allow us to, um, I think unlock a lot of, uh, differentiated um, um,
Opportunity. So, we're going to continue with that, uh, for now, we, we are open and always looking for other, uh, opportunities, as well. Um, but, uh, right now and I'll hand over to Andrew, we're we're well placed to fund the, um, the, the programs that we have certainly after we did the reset that we did Andrew. Yeah, thanks John. Um, so so the way I think about Capital allocation for at least the next year, or 2. Um, the company has has had significant spend on the on the vet, Daga strand, um, phase, 3s the last several years you're going to see those costs start to ramp down and what's going to happen is that those costs are going to be replaced by a series of phase 1, early phase studies, right? So, we're making a bet on the early stage programs. We, we love them. Um, we can't obviously write down tell you which ones we're going to take through on our own and
Which ones were going to license. We're going to push on all of them. We think that many of them are highly highly promising, um, and we'll be making decisions on those as we go through the development pipeline. So we, we look at these, um, programs all the way out. Um, you know, obviously we've known about our programs for a long time, so they've been incorporated into our spend, um, you know, even before we announced that they were coming into the clinic, so this is not a surprise to us, um, and we're just delighted. So we're going to continue pushing on our Phase, 1 programs, and we'll make decisions as we go through based, on which ones we think make the most sense for us to keep and which ones make the most sense for us to partner, potentially,
Thank you so much. Thank you so much.
Your next question comes from the line of tazeen. Ahmed with Bank of America. Your line is now open
Hi, good morning. Uh, thanks for taking my questions. Um, just
As it relates.
You know, to just given the current data that you have and buy a markers. Let me think about the translatability of of those. And the clinical end points as it relates to, to PD. And then, um, I just wanted to know about once you show the PD data in 2026,
What do you think is going to be your area of focus? That'll allow you to support the advancement into a phase 1, B study into PSP. Thanks.
Thank you. Great question. Not sure. Thanks, John, and uh, good to hear from you, Tazeen. So, uh,
Yeah, 102. It's just such an exciting story for us because, you know, just to review and build off of what John. And Andrew just said, if you think back, we've been working in oncology but also developing neuroscience. And here we are on the heels of a
positive registration study for vep 2 out licensing of luide and our degrader to Novartis and where advancing to oncology drugs in here. Now, we have rviz in this direction for PSP and possibly for Parkinson's Disease. So for years of over the past many years, there's been tremendous investment in the Parkinson's disease community. And the PSP Community to understand what are the pathways that drive this neurodegenerative disease. And so there's the large large biomarkers, uh, study called ppmi. And this looks at the natural progression of Parkinson's disease, and it is demonstrated that there are
Who are scientists more, broadly? Because we showed that, in healthy volunteers we're able to reduce these biomarkers, right? And now we're running the Parkinson's disease study. That is looking at all of these biomarkers and we expect that if we degrade bark 2, as much as we saw in healthy volunteers, where we achieve 75% reduction more than enough um to to advance this into uh PSP. And PD studies, that we should be able to drive down these biomarkers, that caused the neuroinflammation and the Mist trafficking of proteins such as Tau. Uh, so building on that, you know, we, we have the healthy volunteer data, we're going to report out our, um, Parkinson's disease, Mark to degradation and, um, and biomarker data. And then next year things go right? Start a PSP study. PSP is a nerd degenerative disease.
That relies also on this Mist trafficking of Tau. And we know that our drug can correct this Mist trafficking, it can, um, improve the, uh, you know, decrease the neuroinflammation. That is also at a root cause of PSP and will be treating patients for, uh, continuously meaning no longer just limited to 28 days. Uh, continue to accumulate biomarker data and
Correlate that with clinical measures like psprs and others and we will hope to report out in short order, the results of the of that phase 1B study. And if things go, right, we uh, may be able to start a phase 2 study even before we have the um the phase 1B study has completed. So you know a registration quality Phase, 2 study. Uh but exactly guiding on, when that can start that, you know, we have to await, you know, clearing R&D I indeed and starting the phase 1B study.
And just to add to that, you know, we do know that human genetics point to Lark 2, um, and Lark 2 is elevated, um, in the brain of patients, but an idiopathic Parkinson's disease in microglia as um, Noah stated and then also, in Progressive super nuclear policy these same Snips that elevate Lark to also Drive increased progression.
In a clinic clinically meaningful way and time to death. And so, you know, by going in with a, a clear way to modulate the Lark 2 pathway, um, we feel that we stand the best chance of proof of proving the Lark 2, um, hypothesis in disease in both, um, Progressive super nuclear policy and potentially Parkinson's disease.
Your next question comes from the line of Paul Choi with Goldman Sachs.
Your line is now open.
Hi, good morning, and thank you for taking the question. I want to check if you might have any additional dosing cohorts for arv, 393 at the upcoming Ash meeting including, uh, ones that might potentially be in the, uh, the target therapeutic range for, uh, where you're that, you're aiming for and then on arv. 027, I'm just curious, if you thought of other CAG, repeat related diseases, and uh, being potential areas to explore, including Huntington's, or other neuromuscular diseases. Beyond The Final store valer that the focus on initially. Thanks for taking the questions.
Yeah thank you. Um no and Angela could probably cover those. Sure. So did the first question of 393, uh you know we've given particular guidance here I think we would have uh like to be able to give a full updated Ash this year on uh 39 you know our dose escalation in 393. But in fact we uh are not yet in what we had anticipated to be the were predicted to be the um the application's range, although fascinatingly to us and uh very promisingly in our data.
Hanging. So, we wanted to share that we're making progress and we're seeing, um, efficacy and tolerability of the drug, uh, regarding the o27 question, I'll turn it back to Angela. Sure. Great. Um, o27 we selected based on its unique profile for, um, degrading the polyglutamine, repeat Androgen receptor in the nucleus and the cytoplasm, which is really important for a disease driver for spinal and bulbar muscular atrophy and we reported out. Some. Very exciting data showing that we rescue um, muscle function, including grip, strength and endurance to end of phenotypes that are really important um, for patients with that disease. So that's a very exciting. Um, opportunity with respect to polyglutamine repeat expansion disorders. We have a robust approach. Um we're taking to those um repeat disorders. We're taking a 2-prong approach. Um also for
Huntington's disease, um, for Huntington's disease, we have identified, um, selective lions for mutant huntingtin, um, and sparing wild types. So we're continuing our efforts. Um, we're early, but we're making good progress there. And then also the idea of tackling, um, repeat expansion disorders. It is something we're taking very seriously and, um, we have a very, um, unique opportunity there as well. So that
Early. Um, but very exciting space for our Venice.
Just, um, 1 more comment if I could build on that. So look when we go into the uh, sdma, we're starting in healthy volunteers. But the appropriate thing to do the great opportunity here is this disease is you know, it's basically a monogenic disease, we know exactly what the target is. The poly g r and we know from we know that we can degrade it. So in healthy volunteers, we're going to be able to also do muscle biopsies if if permitted and it's going to be very validating very quickly for this technology. So it's the perfect setup for a for us to enter a rare disease space because we can get to results in a conviction about our, our pathway engagement in healthy volunteer studies, which is an unusual opportunity.
Thanks move.
Your next question comes from the line of Jonathan Miller with evercore. Isi, your line is now open.
Uh, hi guys. Thanks for taking my question and congrats on all the progress in the early pipeline. Uh, I'd like to start with cos
I'd like to start with COS combos. If I might, you mentioned a couple of interesting potential combo partners for the COS program—things that other players in the space maybe had trouble combining with given tolerability profile. How early could we get into combo cohorts? Is this the sort of thing that we could expect to see even in expansion cohorts starting next year, or should we think about combo partners and beyond maybe being a little bit more delayed from that? And then secondly, just on the HPK1 program, that seems like it's obviously very early still, but potentially pretty interesting. I noticed not much on the deck. When would you expect to show us more of that preclinical data and give us a sense for what indications maybe are the most fruitful for early looking there?
Great questions. And I'll use my usual double act here of Noah and Angela to answer something.
Thanks John. And thanks for the question. Yes. So to field the, uh, 806 question. Um, yeah, you know, we're not guiding yet to the timing of combination so, you know, it would be speculative on my part, but I love speculating. So, uh, the bottom line is where really tearing through our dose escalation
Right now, uh, cuz there's tremendous interest in this and, uh, tolerability it seems for patients. And so, the ideas, we are planning to go into that combination immediately after we do some, uh, we don't even have to wait till we have our expansions read out completely. Uh, we could start that earlier so, you know, we're hopeful that things go very fast. You know, it might be something we could start next year, but I can offer guidance. It's all going to be, uh, clinical data dependent on.
Right, but certainly possible.
23 our hpk1 degrader. And so, we're very excited about the opportunity for that degree. It has a very differential profile with respect to both, um, pd1. Um, and also the kinase inhibitor, the hpk kinase inhibitor that's in the clinic. So, what we've been able to show and what you'll hear about at sissy, is the impact to T Cell exhaustion and importantly, the impact of the T Cell micro environment we are seeing dramatic changes there and outperforming anti-pd1 and hpk1 Inhibitors in both low and high immunogenic tumor models pre-clinical. So stay tuned. You'll hear a lot more about our oral immunotherapy that we think will will outperform. Um, and also be very useful in the
Setting that is resistant to checkpoint blockade. So, um, we have a lot of enthusiasm around that asset.
And your final question comes from the line of Andrew Baron with Ling Partners, your line is now open.
Hi, good morning everyone. This is Amanda on for Andy, thanks for taking our question. Um, we wanted to know, uh, what you've learned about drug drug interaction with Fab that gives you confidence. You won't be seeing similar interactions with the new degraders. Is there something hassles or how they're metabolized in different or similar ways? Um, thanks so much.
Yeah. Thanks to the questions. I mean in general protects a lot of different from small molecules in terms of um how you'd analyze them for DDI. Every single molecule is different, they get metabolized differently, the interactions of the molecules, definitely. So there's not a generic um answer on protacs because every single flow Tech is going to be unique and different. Um, so yeah, some some components like many drugs. Uh, you look at to see how the metabolites see if they have a drug drug interaction. You might see some of that you might not. That's exactly what we're seeing with prototypes. So there's no difference between a protac and it's DDI potential versus any small molecule.
Got it. Thank you.
There are no further questions, I will now turn the call back over to Mr. John Houston for closing remarks,
Well, thank you very much and thanks for everybody's, uh, great questions. As you can tell, we're very excited about this next wave of, uh, programs coming through our early development Pipeline and, uh, we're going to be excited to tell you more about them in the coming months. What a lot of interesting data coming out. So again, thank you for your time.
Ladies and gentlemen, that concludes today's call, thank you all for joining. You may now disconnect