Conference Transcript - ANL 2026-09-14

Bob Klingenberger, Analyst — Morgan Stanley

Afternoon, everyone. My name is Bob Klingerberger with Morgan Stanley. Excited to welcome the Adelaide Norte team here to our conference. Just before we get started, I just want to refer everyone to the Morgan Stanley Research Disclosers website. And if you have any questions, reach out to your Morgan Stanley representative. Like I said, very excited to have the Adelaide Norte team here. I'm joined by Brittany Stopa, Director of IR, and Alex Yee, the CFO. And we'll be diving into some good questions here. So thank you guys for coming.

Alex Yee, CFO

Thank you for having me. Thank you for having me.

Bob Klingenberger, Analyst — Morgan Stanley

So maybe just to kind of start off, you know, you all, I think, kind of describe the strategy of the company and really kind of the two pillars, both the precision RAS targeting therapy kind of platform and then a next-generation PD-L1 pathway modulation. Can you just kind of talk about how you feel like at a high level those two come together and kind of form the portfolio that you all have today?

Brittany Stopa, Head of Investor Relations

Yeah, great. Well, thanks for having us, Bob. We're really thrilled to be here at the Morgan Stanley Conference. So, Abai Norte is a clinical stage biotechnology company that's targeting RAS from multiple angles, and we have a mission to transform deadly cancer into a chronic and eventually curable disease. Now, we're approaching that with, we have a global team which has operations in the U.S., Singapore, and China, and we have an in-house R&D team that has synthesized over 1,000 RAS-on inhibitor molecules. And we have a proprietary RAS-seca platform, which is our RAS inhibitor conjugated antibody platform. Now, we are advancing first-in-class and potential best-in-class molecules with our three lead oncology assets. We have two innovative RAS modalities, so that includes AN9025, which is a potential best-in-class pan-RAS-on inhibitor oral small molecule, and AN4035, which is a first-in-class pan-RAS on inhibitor ADC targeting CECAM5. We also have a next-generation immunotherapy that's AN8025. That's a potential first-in-class multifunctional T-cell APC modulator. But for now, our focus is squarely upon our RAS programs, which we think could be quite differentiated in addressing the over 175,000 patients diagnosed in the U.S. every year with RAS-addicted PDAC, non-small cell, and colorectal cancers.

Bob Klingenberger, Analyst — Morgan Stanley

Great. Well, you know, I think in terms of the RAS platform, I mean, probably we should just start. You kind of introduced 9025 and 4035. I'll try and get those right throughout the questions. Maybe just to start on the, you know, the small molecule PANRAS 9025, you know, just maybe give us a little bit of kind of overview of the molecule and where you all sit today in terms of development. We'll dive into some of the details from there.

Brittany Stopa, Head of Investor Relations

Yes, AN9025, like I said, is our PANRAS on inhibitor oral small molecule. Now, that's been developed all in-house. It's been developed to address multiple RAS mutant solid tumors. And so the way that we've designed the molecule is that it has about 250X higher potency relative to the first-generation pan-RAS-on inhibitor, diraxon-RAS-ib. And that higher potency is driven by stronger CYP-A binding and slower dissociation, as well as stronger binding to RAS-on and slower dissociation. So you get a more stable tricomplex formation. And then that is leading to what we've seen in the preclinical setting, including more durable RAS signaling inhibition, deeper tumor regression, and more delayed adaptive resistance formation. And so we're excited about the potential and what we're seeing in the preclinical profile there, and we're hoping that translates into the clinic. So right now, we're in the global phase one trial. We began enrolling patients in the QD arm in February, and then in July we actually activated a QW arm. And that intermittent dosing schedule was enabled by, like I said, that preclinical profile and the durability of signaling inhibition that we saw. Now what we'll look forward to doing is we're continuing to dose escalate on both arms, but we're looking towards providing an update in the first half of 2027 on that program, which will be the full phase 1A data for the QD arm, as well as an early look at the QW arm.

Bob Klingenberger, Analyst — Morgan Stanley

Great. You referenced some of the preclinical data, both on potency and durability and half-life. Maybe just as we think about that first half, 27 disclosure, or, you know, what should we be kind of looking for to demonstrate sort of, you know, that kind of best-in-class potential that you've been talking about?

Alex Yee, CFO

Yeah, I think for the molecule 9025, if fully translated like 100% from preclinical to the clinical, I think we would be expected to see a better safety and tolerability profile, also with a better efficacy compared with the current players. But this needs to be 100% translated. I think right now, based on the initial clinical data we see, it's a little bit early, but I would say it's not far away. Probably we need probably two or three months to really understand the profile. Initial, as Brittany mentioned, we already released to public, like we just initiated the expansion cohort. for our QD dosing for the small molecule, which implies we have been seeing pretty good human PKs data compared with highly correlated with what we see from pre-clinical. We also are being observed and seeing preliminary efficacy with better tolerability profile in the human data.

Bob Klingenberger, Analyst — Morgan Stanley

And I know you all have, you know, in your corporate deck, to an extensive kind of preclinical package. Any particular kind of data, especially as you think about relative to, you know, some of the other players in the space that you want to highlight as we sort of are thinking about expecting the clinical data next year?

Alex Yee, CFO

Yeah, I mean, as we're always saying, the reason we initiate the human data is we want to really further confirm with the preclinical finding. But if you're just looking for a few preclinical data how we've been demonstrating our corporate deck, we have been doing very extensive preclinical CDX model to compare our molecule with color market players. I think with all those G12X, G13X CDX model, we have been showing very good deeper tumor inhibition in the in vivo level. We also showing potentially in the QD dosing, we have a very comparable Cyreputis window with the RASM-RECIP in a preclinical head-to-head study. We also potentially showing the weekly dosing can further open the therapeutic window while we didn't compromise our potency improvement. In the animal, we had been able to show over 200 to 254 more potent in the animal in vivo data, but we didn't compromise for the therapeutic window's loss.

Bob Klingenberger, Analyst — Morgan Stanley

Yeah, and you touched on, I think, where I wanted to go kind of with the next question, just in terms of both the QD dosing and then the weekly kind of intermittent cohort that you started this summer. I would be really curious to hear a little bit of how the internal thinking is around which one of those, kind of how you look at both arms playing out and in parallel and what you're looking for in terms of what you might be taking forward as you advance the program further.

Alex Yee, CFO

So the idea we initiated QD dosing early this year for our oral small molecule is we hopefully were able to see the differential just by the QD dosing, which is very comparable with what other market players is doing using once a day of the dose regimen. So by the QD dosing data right now, we have been feeling very comfortable. We just initiated dose expansion, but we also shared to public and investors saying we are not reaching the MTD yet. We continue to doing dose escalating the QD dosing. And of course, we also initiated weekly dosing about two weeks ago, two months ago, but we want to highlight that we are not, we initiate the weekly dosing is not because we are not able to really do the daily dosing, it's just for the weekly dosing give us additional optionality we will be able to see by the weekly dosing whether we can further improve the tolerability and also potential push higher dose in humans. In our preclinical data we're showing the weekly dosing actually were able to further open a therapeutic window. We know in the animal, for the QD dosing, potentially we will reach the MTD in about 0.2 milligram in red in the animal. But for the weekly dosing, we actually could push to about 2.8 milligram in animal, which implies a potential at least double of the therapeutic window extension. But everything finding on the preclinical need to be transferred in humans, which is right now we're doing in the weekly dosing in human. But I want to highlight our development strategy on the frontline PDAC, which is the most immediately and most time urgency indication. We were probably just starting that combination in a QD regimen. We don't necessarily waiting for the weekly dosing data. We can always, you know, testing the weekly dosing while we have a QD dose regimen combination. data.

Bob Klingenberger, Analyst — Morgan Stanley

Yeah, and I think what you started to touch on, I think what my next question was going to be, which is great, in terms of maybe just, it's obviously, you know, early in dose escalation. Help us, right, this is pan-res on, you know, broadly expressed, could be very, you know, could be a very broad development plan. Like, where are you, you know, where are you sort of in terms of thinking through tumor types to focus on, combinations, just maybe kind of help us understand at least the current thinking as we're expecting this data.

Alex Yee, CFO

Yes, and we believe it's a potential based-in-class profile of the PenRAS program, PenRAS-owned program. For us, I think the combination is really the very key strategy to moving forward in that development strategy. So first I want to say in China, For our Chinese partner, Axe Pharma, they certainly can follow what we may have been doing in the U.S. because China is still relatively early days. So they certainly will go with the monotherapy in second-line PDAC. And, of course, they can look for a non-small cell lung cancer in China. And for ex-China, which is our going to response for the development, we are going to focus on the front-line PDAC as the combination strategy because in our development strategy, we always, about one and a half years ago, we already know we're going to avoid a second line. And in frontline PDAC combination, we actually first going to try the chemo combination. Based on our current data, we believe we're going to move in the QD dosing as the initial combination dose regimen with chemo. We're going to try two different chemo. One is the GMP. the other would be for phenolox in the front line P-DEC. It's an initial combination. And once we see a very comparable safety, we probably can move into a discussion with USFDA for the registration pathway. Besides the chemo combo, I know there's multiple precision agent combination is being discussed. For example, like PRMT5 and also other agents in the clinical stage, I think there will be also available option for us to consider combination. And then when we're talking about lung cancer, I believe the market opportunity is still quite open, especially if you can come up with a better tolerability profile molecule. Then you can consider the front-line combination with the IO and with the ADC. So it's a lot of options there. So I think our strategy is one to initiate a combination as soon as possible to really showing some combination data, hopefully in 2027.

Bob Klingenberger, Analyst — Morgan Stanley

And how do you, you know, how do you think about the weekly, you know, intermittent? Could that be helpful as you explore some of these combinations, right, because, you know, to some of your earlier points?

Alex Yee, CFO

The time-sensitive indication like a frontline PDAC or lung cancer, we don't necessarily wait for the weekly dosing data because the QD dosing data may be good enough for the combination. And I think the time to the market is also very important. so we are not going to wait for weekly dosing data. But for some of the indications, like colorectal cancer, we might still have some time, and then there's not that many pain loss players showing the colorectal efficacy data or higher response rate yet in the CRC indication. So for that regard, potentially a weekly dosing could be showing some benefit to try those hard-to-treat indications. We have a decision process. is at a certain point when we are going to view the Q-week dosing as showing a benefit, but really 100% translate from preclinical to human. There would be, we're going to look at the MTD or the RP2T dose for Q-week dosing or for the QD dosing. If at a time the total weekly dose of the Q-week would be larger than total weekly dose of the QD dosing, then we can kind of make a decision and say, okay, the Q-week dosing really showing a differentiate, and potentially we can maybe testing the Q-week dosing in certain indication. But right now it's too early to tell. We just initial the Q-week dosing, and time will tell.

Bob Klingenberger, Analyst — Morgan Stanley

Okay. And maybe then just kind of back to the overall first half disclosure, right? I appreciate it's ongoing, the trials, but could you start to give us maybe a bit of a sense of, you know, what we should be expecting in terms of, you know, kind of number of patients, you know, efficacy, safety, initial kind of data that you might expect to disclose. Sure. Brittany.

Brittany Stopa, Head of Investor Relations

Yes, so as you mentioned, they're still in the dose escalation portion of the phase one, so it's difficult to provide an estimate on the number of patients at this stage, also because we're doing the backfill. So the number of patients that we'll be able to share is still not yet disclosed. But what I can say is that we're aiming to provide a really fulsome update and to give a comprehensive look at what our phase 1a experience is with the QD dosing. So we aim to provide a meaningful number of patients at an interpretable dose level with a meaningful amount of follow-up because we understand that there are other data sets out there against which our data will be benchmarked. And so we want to tell a compelling story with the data that we're able to share. And then with the QW arm, with the intermittent dosing, because we're the only RAS on molecule that is exploring intermittent dosing in the clinic, we think that setup is a little bit different. And so if we're seeing some early signals, that could be interesting. And so that's why we're guiding to sharing an early update on the QW with the first-half data.

Bob Klingenberger, Analyst — Morgan Stanley

Yeah. And I guess as we think about, right, some of the external data sets that exist and are out there today, any in particular that have kind of caught your eye as you think about some of these development strategies and where 9025 could really kind of differentiate fit in in the paradigm?

Alex Yee, CFO

You mean the current data from other panelists?

Bob Klingenberger, Analyst — Morgan Stanley

Yeah, just in terms of how you feel like 9025 can really kind of stand out, differentiate relative to some of what you've seen so far.

Alex Yee, CFO

I think the only thing we'll be able to differentiate you much to showing your human data and then of course right now we're showing a great preclinical profile and the only thing we need to show is the human data which is not far away from now so I would say if a molecule you really can claim is a basing class or is a better molecule as a next generation molecule you need to show it's a much better tolerability and also in the efficacy of those you will be able to show comparable efficacy which means like overall response rate and ideally I don't think next year we're going to show the always data yet but at least it's the overall response rate in PDAC indication of overall response rate in a non-small cell lung cancer we need to at this benchmark with the current market players, which we have two players showing the clinical data like Remed and Eurasica. So I think we need to show a better tolerability and also comparable or maybe better efficacy to really can claim as a better molecule or best-in-class molecule. But again, I want to highlight the current RAS market is very big enough. It's about 20% or 30 tumor with the RAS mutation. So even come with the mid-2 molecule, you know, it's a third place. You still have a lot of angle to play. For example, the combination would be a huge opportunity. The current players, majority, they're showing the monotherapy data. So I believe the combination is really, you know, the opportunity is there. But we also have the potential to show difference as the preclinical profile showing a potential next gen, but just want to be conservative here before we release the human data.

Bob Klingenberger, Analyst — Morgan Stanley

Yeah, great. So, you know, I think the second program that, Brittany, you mentioned at the beginning, too, that I know had some exciting news last week, kind of entering the clinic, so for 4035, you know, now that the first patient, you know, has been dosed and your, you know, IND has been cleared, you know, So what are, you know, kind of maybe talk a little bit about kind of the thesis behind this molecule. Obviously, we spent a lot of time on the PAN-RAS-ON and what, you know, you're sort of hoping the initial clinical data can prove out for that molecule.

Alex Yee, CFO

Yeah.

Brittany Stopa, Head of Investor Relations

Yeah. So AN4035, like you mentioned, is our antibody drug conjugate, ADC. But instead of a cytotoxic chemotherapy payload, we use a PAN-RAS-ON inhibitor payload. So it's a first-in-class molecule to do that, actually a first-in-class molecule to our knowledge to have a precision oncology payload on an ADC. So we're really excited about the potential there. This comes out of our Resica platform, and this is the first molecule to come out of that platform. We've selected as our target CECAM5, which is highly expressed in colorectal cancer. And so what this mechanism of the ADC allows is more targeted tissue delivery of the payload. And in our preclinical experience, we saw that we're able to deliver a higher potency of the higher load of the drug to the tumor and provide a better balance with the systemic toxicity. So we're excited about the potential for the ADC. Like you mentioned, we just chose the first patient. We shared that news last week. So that global phase one trial is ongoing now, And we're running that trial with two arms. We have a monotherapy arm and a cetuximab combination arm, which will have a staggered start. And our goal is to have the full Phase I-A data for that program available in the second half of 2027.

Bob Klingenberger, Analyst — Morgan Stanley

Yeah. And I guess, you know, I know the goal in the study, too, is, you know, is a decam-enriched population. And so, you know, maybe just if you talk a little bit about kind of how you're going through the patient selection process and, you know, how that, you know, may interpret some of the kind of early data and maybe just a little bit more about the combination versus monotherapy, where you're focused there.

Brittany Stopa, Head of Investor Relations

Yes, so we're running the phase one as a basket trial. So we're enrolling solid tumors with RAS mutation. And now for the big three, PDAC, non-small cell, colorectal, we're not requiring elevated CEA levels for enrollment onto the trial, but for tumor types outside of the big three, you would just need to have an elevated CEA level. And circulating CEA, it's a common tumor marker, so physicians are able to order that in the And then, you know, certainly on the back end, we will be looking to better understand how CECAM-5 expression levels relate to the ADC activity. So our scientists would plan to conduct immunohistochemistry studies to understand the CECAM-5 expression levels.

Bob Klingenberger, Analyst — Morgan Stanley

Yeah. And I know, you know, the platform you all have is, you know, this is, you know, producing a first-in-class molecule, entering the clinic. You know, maybe as you just think about kind of future strategy, you know, there, maybe just if you describe the platform a little bit more for us because, you know, I think it's produced, obviously, a first-in-class, pretty interesting molecule to start.

Alex Yee, CFO

Yeah, I can share a little bit about this platform. So the idea with going to design this RAS-on-PeloADC platform is we see there's a great challenge on the first generation of pen-RAS-on molecules. So they usually have a very limited combination ability because of the skin and GI toxicity. So we feel it's an antibody targeting platform potentially can address those challenges. And also in current ADC therapy, there's a lack of diversity of the payload mechanism, which in this year you see a pharma company is starting that acquisition for a lot of newer payload mechanisms company, which is further weighted our approach. So we have designed an internal linker payload would be able to conjugate with the Penroth's own payload, and then we can select a certain target antigen. For example, the first program we're choosing is a CKM-5 ADC. This is the program as AN4035 we designed. And thank you for our great understanding knowledge for our internal discovery team, because we initially working on the Penroth's own approach It's about five years ago, so we built up quite a lot of knowledge, and also we had over 1,000 molecules that would be able to allow us to quickly select the most base profile panel. And this platform would be a platform play, so besides the CK5 ADC, we also were working on other types of target antigen, and potentially we could also combine with other payload in the near future for the ADC. I want to do a little bit of an expansion for the CKM5 ADC's development strategy. I think the idea is we, of course, recruit all the RAS mutations, sorry, cancer patients, but with the CEA enrichment. We hopefully were able to see a potential response in the colorectal cancer patient because this indication is very difficult to treat. and of course we could also see some combination data as well as Brittany mentioned we initiated EGFR combination in quite early stage we actually designed a staggered design for the combination study and potentially for the ADC study we will also potentially in the expansion cohort we will also enroll a post-derazone patients as well, and we want to see what kind of a profile it looks like for those type of patients to receive treatment for our ADC.

Bob Klingenberger, Analyst — Morgan Stanley

Yeah. Excuse me. And so, you know, next year promises to be a pretty, you know, data-rich year in terms of the disclosure for 9025 and 4035.

Alex Yee, CFO

Maybe just as you've done, you know, several financings this year, maybe just kind of remind us in terms of kind of current cash runway what you know kind of what is you know what is for you know funded with your current current cash yes so early this year we did a tool financing a pipe financing so of course thank you for our current shareholders from coming from those pipe financing they provide a great support for our current two last programs development so by end of the June 30, we have a total cash is about $232 million US dollar cash. This is good for us to get through the 2028 and allowing us to really testing the preliminary safety and also a preliminary efficacy, potentially a few proof of concept data for our oral small molecule pain loss inhibitor, including the first ADC, CCAM5 ADC program. And by the first half of this year, of course, once we're announcing our human data for the small molecule, we're probably also going to initiate some combination data, and then based on those, of course, we were looking to assessor the registration pathway strategy.

Bob Klingenberger, Analyst — Morgan Stanley

Yeah. And now we've covered a lot on 9025, 4035. You know, earlier pipeline, I know, Brittany, and you mentioned some of the other programs, and I know that the focus is on the PAN-RAS, but maybe just spend a moment on where else you all are excited with some of those earlier programs.

Alex Yee, CFO

Yes, so as I mentioned, the CKM-5, of course, the reason we select the CKM-5 is because it has over-expressed in the colorectal and also PDAC tumor, while it has a relative lower normal tissue expression. And also CKM-5 is perfectly avoid skin expression and also they have a very manageable GI toxicity. So CKM-5 actually proved to be a very perfect combo with Penroth's own payload as ADC design. But even it's a perfect combination, but it had a limitation because you might need to look for CKM-5 enrichment tumor type outside of speak three. So you could imagine if we're going to target other indication, for example, for breast cancer, for liver cancer, for other type of solid tumor cancer, they might have also coexist with RAS mutation with other tumor antigen. Then we could ideally see we may be choosing other tumor antigen to target other indication as the following program. And then for the payload itself, the pain loss on payload has specific address for those last mutation tumor but potentially you could also consider a combination with the pain loss on payload with other mechanism of the payload to do as a dual payload program we seeing the fast forward from China they also have some company they're working on the dual panel it's not easy but I think that's something is another mechanism we also being working internally as well. It's a target antigen you could also consider for example like a bi-specific you know it's a target antigen could be also addressing relative different challenges in the current cancer treatment. So yeah so this is a platform play and then we have a lot of ongoing but of course we would focus on our resources on that to lead program, and of course we can consider a potential strategic partnership for a platform of our Nova Payload ADC. Yeah.

Bob Klingenberger, Analyst — Morgan Stanley

No, no, that's great. Maybe as we're kind of wrapping up here, Brittany, you've been with the company a little bit now, and as you all are telling the story, and we've heard it today, what do you feel like maybe is maybe just not as well understood, appreciated about the story that you'd like to kind of re-emphasize for us as we're wrapping up?

Brittany Stopa, Head of Investor Relations

Yeah, absolutely. I think, understandably, there's a lot of investor focus on the most near-term catalyst, the data readout for the 9025 Small Molecule Program, and we're certainly excited to see how that preclinical profile translates into the human data and what we can share with folks there. But we're also really excited about the ADC program. We think the mechanism is really differentiated and could open up a lot of avenues for interesting development. So as we enter the clinic with 4035, we're starting to hear more interest from investors on that front, and we continue to hope that as that story unfolds, we can continue to share that more.

Bob Klingenberger, Analyst — Morgan Stanley

Yeah. Alex, anything you would like to add in terms of where you feel like, in terms of the story, what maybe people are missing where you want investors to be focused?

Alex Yee, CFO

I think right now we will hopefully focus our clinical data of course it's not far away from now and then as we all developers I think really showing the differentiated profile you need to use in the human data to really prove the idea so yeah I think the first half twenty seven would be you know would be exciting time to really the first showing our data and of course the I think the execution is also very important for our current development strategy for our panelists on program so yeah we we like to focus on the execution in 2026 and opposing the data year 2027 and we will be able to report in the data at a time yeah great well you're watching closely thank you thank you both for joining us we're just that time and thanks thanks for being here thank you Bob thank you Bob for invitation