Conference Transcript - MAZE 2026-06-10

Elizabeth Webster, Analyst — Goldman Sachs

Good morning, and thank you for joining us today. My name is Elizabeth Webster. I'm on the biotechnology equity research team here at Goldman Sachs, and today we have with us Jason Coloma, the CEO of Maze Therapeutics. Thank you, Jason, for being with us. I guess to start, can you provide an introduction to the company and walk us through where Maze stands today with your lead assets, 828 in AMKD and 782 in PKD and CKD?

Jason Coloma, CEO

Yeah, well, thanks for having me today. Yeah, so we are, if you will, a small molecule precision medicines company really focused on diseases that really haven't seen precision before, like kidney disease. There's over 800 million people in the world that suffer from kidney disease. It's the ninth leading cause of death globally. In some countries, there's a four-year waiting list for, if you will, a transplant. And unfortunately, there hasn't been a lot of innovation in kidney disease, and that's exactly where we fit in. We developed small molecules, really focused on being able to provide precision for those patients, starting with 829, which is for 8-1-1-mediated kidney disease. There's about a million people in the U.S. alone who have suffered from the disease, and we've taken an approach where we've been able to demonstrate proof of concept in a broad set of patients earlier this year. And our second program, 7-8-2, which is being developed for two particular indications, one for a rare metabolic disease called PKU and also equally excited about what we can do in kidney

Elizabeth Webster, Analyst — Goldman Sachs

disease. Awesome. And you relatively recently presented data from MACE 828 in the broad AMKD population. Can you just kind of go through that data and, you know, summarize what the learnings

Jason Coloma, CEO

were there? Yeah, so it's 829. I'm sorry, 829, yes. That's okay. Yeah, no, so what we did earlier this year is we presented 829 data from our Horizon study, which is a global phase two open-label study. There are a couple things that were accomplished there. One is that we show that it continues to build on its safety as well as tolerability profile. The second thing that we're able to do is across the different cohorts. We had SGS, those without diabetes, and those with diabetes. The third is we showed evidence, at least early and promising, that we have a competitive of profile relative to other molecules that have been described in the literature, in particular in FSGS patients. And the third thing is that we had the ability to show efficacy in more moderate forms of proteinuria, which hadn't been demonstrated before. The totality of that particular data allows us to really accelerate what we're doing in the sense of being able to advance the program into pivotal planning, and we plan to start our pivotal study using A29 next year.

Elizabeth Webster, Analyst — Goldman Sachs

Great. And kind of walking through the different subgroups, can you kind of talk about the signal in the diabetic patients versus the non-diabetic patients, and then how you think about the data in FSGS versus the non-FSGS patients, and just kind of walk us through those subgroups.

Jason Coloma, CEO

Yeah, FSGS, what we were able to demonstrate for the first time was really a group of patients that have been treated on various medications, including SGLT2, which hasn't been described in literature before. So despite being heavily premedicated with other forms of kidney disease agents, we showed a 62% reduction in UACR, which had really exceeded anything that had been described previously. So demonstrating our ability to have at least this concept of being best in class. We were also able to demonstrate for the first time the ability to show efficacy albeit early and promising, the idea that you can go in more moderate patients, both with or without diabetes. The previous literature had really not described a lot of evidence that there would be able to see efficacy at all in diabetic patients. We saw early promising signal in some of the patients, about 40% of the patients showed efficacy, even despite having been previously treated with GLP1s as well as SGLT2s. Great. And when we think about the change in

Elizabeth Webster, Analyst — Goldman Sachs

UACR, I think you've mentioned this kind of 30 milliliter bar. Talk about kind of what's clinically meaningful in these populations from change from baseline. Yeah, if you take a look at

Jason Coloma, CEO

sort of the overall clinical development of other approved agents in kidney disease, 30% reduction in proteinuria translates well to overall, if you will benefit, in looking at other measurements, including what's called EGFR, or filtration rate of the kidneys, which is one of the approvable endpoints for some of the indications in kidney disease. So the fact that you can see a 30% reduction has demonstrated in previous studies to be, if you will, translatable to other endpoints. The other thing to keep in mind is that it really is used in the KDAGLE clinical guidelines, at least in the U.S. A physician and a nephrologist will look at the ability to try to reduce proteinuria by 30% with existing agents. If they're not able to do that, either with dose adjustments or adding other agents, they keep going. So they'll start a patient on, say, what's called an ACE-ARB. They'll try to then see if they can adjust the dose. if the patient's not getting to that 30% reduction, and they'll keep trying to add agents or switch to different agents in order to try to do that. Unfortunately, patients with 8-Ball-1 kidney disease, standard of care is not efficacious in these patients. And unfortunately, despite all going through multiple treatments, including things like ACE-ARBs, immunosuppressants, SGLT2s, they're not seeing that 30% reduction straight away. And so an agent like 829 shows that real promise because we were able to do that across a number of different patients and different types of patients, including FSGS and non-FSGS patients.

Elizabeth Webster, Analyst — Goldman Sachs

Great. And you're kind of targeting some near-term updates on the development path here, but where do you see clinical development for 829 proceeding, and what's your plan there?

Jason Coloma, CEO

Yeah, so to take a little bit of a step back, the data that we had in March was an administrative analysis, that allowed us to really be able to, number one, identify whether or not we had an active compound, which I think we did. The second thing we were able to do is really describe are there any particular cohorts that we think about accelerating and moving to a pivotal study faster, which we were able to do. The third thing is to look for initial signal in more moderate patients, including those with diabetes. Now, with that in hand, we're pushing forward, in particular in the non-diabetic patient population, to advance into pivotal studies, so we accomplished that. And I think what we want to do in diabetic patients is to continue to collect more data. It's early and promising as we talk about that with nephrologists in the field and the way that they might potentially treat their patients that have diabetes and have 8-4-1-1 kidney disease. They find it incredibly encouraging, primarily because they're not responding necessarily to other agents like GLP-1s or SGLT2s. So what we'll continue to do is collect more data, see if we can tease out the signal. We did see response in some patients, as I described. What would be interesting as well is to identify, are there particular biomarkers that might help us enrich to better understand the signal? If you look at the literature in DKD, 40 to 50 percent response rates are typical in DKD patients. And you can see in the literature, even the last approved product for kidney disease, which was Corendia, in their phase 2 study, they had about 20% to 25% reduction in UACR, yet that now is an approved product for kidney disease. And so if we can take that type of learning and better understand, one, can we see UACR reduction in diabetic patients, as well as, number two, figure out are there particular markers that might help us enrich, that will allow us to think about the development plan for, I would say, the diabetic patient population.

Elizabeth Webster, Analyst — Goldman Sachs

If you could put a timeline on those, would you say?

Jason Coloma, CEO

So we'll have the full readout for Horizon, the end of 26 and 27. So we will have the three cohorts of FSGS, non-diabetic patients as well as diabetic patients, 10 to 15 patients per cohort that will allow us to really understand and tease out the signal. In parallel, what we're doing is advancing the non-diabetic patient cohort for pivotal planning, which we expect to start in the first half of 2027.

Elizabeth Webster, Analyst — Goldman Sachs

Okay, great. And then just thinking about the competitive landscape, you know, there are other kind of assets in AMKD and development. Where do you think 829 is most differentiated, and how do you think about the competitive landscape here?

Jason Coloma, CEO

Yeah, I think there's, fortunately, there are new therapies in development. There are no approved therapies for 8-1-1 kidney disease today, and the current standard of care, unfortunately, is not proven to really improve the patient's lives. And many of them, unfortunately, transition not only to end-stage renal disease, but unfortunately to dialysis. And as you know, their outcomes are horrible when you think about if they have to shift into dialysis. And so the idea is, you know, could you develop a particular more precision approach that allows us to really be able to help these patients, and hopefully they'll never have to go into dialysis. I think the opportunity here from our preclinical data, we showed that we had differentiation, especially on potency, which should translate into efficacy. We've actually seen that now clinically early in promising, in particular in the FSGS patient population, which is probably the closest one could think about in terms of apples-to-apples if you wanted to compare it across trials. Always dangerous to do so, but that is the closest one could do. And you can see, even when our patients were treated with many co-meds, including SGLT2 inhibitors, they still had high levels of proteinuria, and we were able to reduce the proteinuria significantly. In the FSGS patients, at 62% UACR reduction, and the non-diabetic patient population, nearly 50% reduction in UACR. So we think that that is not only clinically meaningful, it gives us a differentiated profile relative to others out there that will allow us to participate and really be able to be one of the hopefully cornerstones for these patients. I think the other thing to think about, too, is also in cardiorenal. I think we've all seen this. First is not always best in the sense of commercialization. Order of entry is important, but I think what we can learn from others in front of us is important. We can see that in other areas, smaller CM and in CardioReno, where companies that are coming behind with differentiated medicines, given the unmet need and the size of the population, will have a role.

Elizabeth Webster, Analyst — Goldman Sachs

Great. And just mechanistically, in the preclinical data, I believe you show kind of a dual mechanism for blocking the channel here. Kind of, can you speak to that? Because I think that's an important aspect of driving the potency.

Jason Coloma, CEO

Oh, yeah, of course. Yeah, so I think probably just to take a little bit of a step back in terms of mechanism, what we learned over the years is that 8.001, the way that it causes disease, particularly in the potocytes, or what are called kidney cells, really under certain conditions, you get this overexpression of 8.001, usually an inflammatory response. that overexpression caused it to be expressed in the, if you will, in the cell membranes of the podocytes, basically punching holes in them, because these are ungated channels, and then they have an influx of particular, if you will, bad actors that ultimately cause nephrotoxicity. So you have this overexpression, this ungated channel, and basically having this nephrotoxicity. The idea with an APL1 inhibitor is minimally you want to block the pore from allowing the particular agents entering into the cell. But what 829 does relative to other molecules described in literature is it not only blocks the pore, but it disrupts the assembly of the pore from forming to begin with. We think that's important for a few reasons, but one is that APL1 highly turns over in the protocyte every hour, sometimes as quick as 42 minutes in the literature. So the idea that you want to not only think about blocking the pore, but working upstream, such that the pore is never formed to begin with, makes sense that you would be able to, if you will, change sort of the proteinuria levels in these patients. And so compared to other molecules that have been described, they're only able to block the pore. They're not able to disrupt the assembly. And so that's why it helped, I think, for us partially explain the potency... into the clinic. Again, looking at the FDA, we saw a 62% reduction in that UACR. Previously, in terms of UACR, that was in the high 30s. And our patients were treated on a background of multiple meds, including SGLT2, versus what's been described in literature that the high 30s, the patients were not treated on SGLT2.

Elizabeth Webster, Analyst — Goldman Sachs

Got it. And thinking about what a Phase III trial could look like here, kind of walk through how Maze is thinking about that. And then, you know, your point about the background therapies. Is that kind of similar to how you would think about patient enrollment in such a study?

Jason Coloma, CEO

Yeah, I think what's nice, there's an academic working group called Parasol that was started at the University of Michigan that was really helpful for other companies working at FSGS. There was a recent approval, which was great for FSGS patients. and that particular academic working group that they were working with the FDA they're now working on 811 kidney disease so the good thing is we now know for FSGS patients alone from the previous parasol study is that protein area reduction is the approvable endpoint not a surrogate or accelerated approval that is the full approval endpoint so I think it's pretty clear in terms of regulatory path for FSGS patients. What we might be able to learn from the parasol study that's supposed to read out for 8-Ball-1 kidney disease this year is how that applies for FSGS patients that have 8-Ball-1 variants. So it may be the same guidance or it may be different. We'll have to see what the working group comes up with, but I think that will be very important to help clarify the regulatory path. For non-FSGS patients, I think you can look at other studies that are there where they're combining both protein or a reduction as well as EGFR slope as a basis for accelerated approval. That would be highly informative if that's going to be possible, I guess end of this year or early next is that will help clarify at least for our program as well the ability to kind of think about the non-FSGS patients. So I think in summary I think FSGS pretty clear, regulatory path in terms of protein or a reduction and I think we're going to learn a lot from other programs as well as the Parasol Initiative that will inform us how do we think about the non-FSGS patients.

Elizabeth Webster, Analyst — Goldman Sachs

Got it. And just kind of double-clicking on FSGS, could you kind of speak to how that population is kind of diagnosed and just like the term of FSGS, kind of what that means clinically and how those patients might be different if they are than the non-FSGS population.

Jason Coloma, CEO

Yeah, I think there's been a lot of education as you're inferring about what FSGS is. And it's not a clinical diagnosis. It's a histological diagnosis by looking at a biopsy. And historically, kidney patients weren't biopsied that often. It wasn't something that nephrologists had done. But I think to the credit of other companies in front of us and, you know, now approved therapies for those patients. We're learning many more patients are being biopsied once they get referred to the nephrologist. In particular, that's helping them direct them to better care. So I think that's important to note. But typically, you know, APO-01 kidney disease patients, they are disproportionately affected in the black community. So a younger individual will go to a primary care physician. They'll have elevated blood pressure, typically, and for unknown reasons. They get the typical workup that you or I would get if a physician saw that type of blood pressure. They'll look at their liver, their kidneys, and if they come back, they'll see, even if in trace amounts, proteinuria, they'll ideally refer them to a nephrologist. Now, what a nephrologist will do at that point is try to figure out if they are from the African-American community. right now, not everyone's being genotyped, but that's being worked on to date with additional efforts in terms of, I would just say, advocacy in the community. But we're seeing more and more people being genotyped. And then, more importantly, getting biopsied. That's allowing them to direct

Elizabeth Webster, Analyst — Goldman Sachs

them to their to the right care and maybe we can move to PKU and yeah um maze 782 and uh I think it'd be helpful just framing the data that you've shared to date and kind of contextualizing it um

Jason Coloma, CEO

for us in this disease yeah so last fall um we described uh 782 um and and published the phase one data which was over 100 healthy volunteers and what we were able to do there again show that it was safe tolerable pk was linear and predicted well and what we half-life about 11 hours that allows us to kind of think about either once or twice a day dosing but more importantly what we're able to do is show pharmacodynamic effect in particular biomarkers that translate well to PKU. Now, for people that are not familiar with PKU, it's a rare metabolic disease which is left untreated. Unfortunately, you have this toxic accumulation of an amino acid phenylalanine in the blood. And what that does is, unfortunately, some of it makes its way to the brain, causing some neurodevelopmental neuropsychiatric impact. And so right now, the standard of care is to either take what's called a BH4 cofactor or an enzyme substitution therapy, which basically tries to break down that phenylalanine accumulating in the blood. Unfortunately, not everyone can tolerate these, or it's not efficacious enough to really be able to reduce. And so the magic number that you hear right now is that you would want to try to reduce phenylalanine levels of below 360 micromolars in the blood, maybe even 120 micromolars in the blood. Okay, so clinically that's what you're trying to do. And so unfortunately, because not everyone is doing well on these therapies, 60% of the people out there have to stay on this really onerous medical diet where they can have very little protein. And what I mean by that is most of them can have maybe up to 10 grams of protein a day. That's basically two eggs. you and I will probably have eight, ten times that much in a given day. So unfortunately, people have to be on this onerous medical diet, and then they can't come off of it, and they're on it forever. So a new therapy like 7A2 provides an opportunity to address not only the patients today who don't respond to current standard of care, but also the 60% of people who have to stay on this medical diet and ultimately try to get them off that. Because as we talk to patients, parents of those patients, they just want to get off this diet. And if they can do that, that will transform the way that they live because they don't have to be restricted so much and live hopefully more healthier lives. So the data that we published, there was another company who had demonstrated proof of concept of inhibiting SLC6A19. SLC6A19 is a cell you transport or express in the gut and the kidney. And all we're doing is basically hitting the target getting rid of that toxic accumulation of phenylalanine in the blood by excreting it out in the urine. It's that simple of a mechanism. And the good thing about that is you can measure, even in healthy volunteers, how much phenylalanine is excreted out into the urine. And we know that that translates very well to the plasma fee reduction eventually in patients. So there was another group that had published a few years ago that they had, in healthy volunteers, shown a tenfold increase in urinary fee relative to baseline at one of their doses, showing that proof of mechanism. And eventually, in PKU patients, they showed a 40% reduction in plasma fee. And the good thing about plasma fee reduction, that's the approvable endpoint. That's not a surrogate or accelerate. That's the approvable endpoint. So we knew where the bar was. If in healthy volunteers, we can beat a tenfold increase of urinary fee relative to baseline, we would have evidence that we could be best in class. And what we did last September is we showed that many doses were able to beat that up to 40 times. So over four times greater urinary fee excretion than what has been described in the literature to date, which should translate into best-in-class plasma fee reduction in patients when we run that study, which we're running right now.

Elizabeth Webster, Analyst — Goldman Sachs

Great. And in terms of kind of the mechanism and the structure of 7.8 to help us understand points of differentiation, I think there's another oral substrate reducer in development from another company. And so how do you see that kind of biologically and mechanistically differentiated?

Jason Coloma, CEO

Yeah, that's an important point. So at the end of the day, people want to just get off this medical diet. And that means getting their plasma fee as low as possible, ideally below 360, even below 120. So if we can do that, we can get them off the medical diet in the long term. So preclinically, we showed that we were three to four times more potent. And we had talked about that before. And in the clinic, even in the healthy volunteer study, we reinforced that. You know, they showed at one of their doses a tenfold increase of urinary fee relative to baseline. we showed over 40 times increase of urinary free excretion. So reinforcing that three to four times potency relative to anything that's been described in the literature to date. And what that should translate into is better plasma free reduction in patients, ultimately resulting in a number of people who can get below the 360 and the 120 numbers that are important clinically and get them off, more importantly, this medical diet. So what we know about the agent that you described earlier in their phase two study, what we know is that at their low dose, they had about a 40% reduction of plasma fee. At their high dose, they had a 60% reduction of plasma fee. So we have a good mapping of where they are and what the bar is set. And they also had, of the 19 patients that they reported, they had three that went below 360, and they only had one that went below 120. So clearly proof of concept was demonstrated, but there's room to go there. If you think about those numbers, most patients that have PKU are called severe or classical. And what that means is that they have a greater than 1,200 micromolar of plasma fee. And so if you want to reduce that down to 360, if you just do the math, that's 70%. I said at their top dose they were at 60, so they won't be able to serve all of the patients that way. And so with our potency, our early clinical data, we have reasons to believe that we can beat those numbers.

Elizabeth Webster, Analyst — Goldman Sachs

And could you kind of talk about the prevalence numbers and the addressable population sizing? And then when you speak to that 60% of patients that are on that medical diet, how big is that population in terms of the size?

Jason Coloma, CEO

So from a global perspective, there's about 60,000 people that have PKU. About 60% of those are still just on a medical diet. Less than 10% are on an enzyme substitution therapy. And unfortunately, not everyone responds to that because they develop antibodies over time. It also has some issues in terms of safety. So it has less than 10% usage, even though it is the most efficacious for the patients. And so most patients in that 20% to 30% are using what's called the BH4 cofactor, which is basically just a cofactor to allow the enzyme that's there that breaks down the phenylalanine to work better that's what was recently approved with you know another molecule in phase three that's what kuvan is and so our agent works in a different type of mechanism which should in theory work across the entire spectrum of disease because we don't rely on the enzyme that's present to be efficacious, because we just get rid of the toxic substrate to begin with. And if we can do that safely, we should be able to serve the entire spectrum of

Elizabeth Webster, Analyst — Goldman Sachs

the 60,000 patients. And then before moving to chronic kidney, maybe just finishing up on PKU, remind us of your next data catalyst and, you know, potential trial initiation timeline.

Jason Coloma, CEO

Yeah, so we're starting a trial that's a Phase II proof-of-concept study. We have a couple doses that we're doing, plus placebo. So this is not an open-label study. This will be placebo-controlled. So not only are we testing these in a monotherapy fashion, but we also have a third cohort which is going to allow us to look at this in combination with a BH4, just given the fact that we have complementary mechanisms. As we talk to investigators and some of the patients, There's a group of patients that do pretty well on the BH4s, but they can't get below 360, and they can't get below 120. So the idea that we can do clinically is, well, maybe we can serve those patients in combination, get them below the 120 eventually, and they might be able to get off the medical diet in the long run. A lot of investigators encourage us to study those patients, because then if you think about from a development plan, both the low-dose to high-dose and combo, So we potentially can work across the entire spectrum of disease. And based off of our early data, you know, reasons to believe that we can do better than what's been seen before by hitting this target and reducing the plasma fee, which again, at the low dose was about 40% reduction of plasma fee. So we're running a study right now. The data will be in 27. So we have a few catalysts coming up, as you pointed out, eight to nine, end of the year, early next, where we'll have the full horizon readout across the three different cohorts, FSGS, diabetic, non-diabetic, and then we'll also have the PKU data in 27 as well.

Elizabeth Webster, Analyst — Goldman Sachs

Maybe switching over to chronic kidney disease, you know, you've kind of talked about a potential protective mechanism here, and maybe to start kind of what does this mean exactly clinically and mechanistically, what could be driving that? Yeah, so SOC689, we were the first group to

Jason Coloma, CEO

describe the genetics that there's individuals out there in a heterozygous fashion who actually were protected or had renal protection or had healthier kidneys than those that didn't have the variant. That encouraged us to think about, well, could we actually phenocopy what we call the genetics here with a small molecule so that by inhibiting the target, people that have kidney disease might also have that protection so we had not only been able to look at that from the genetics and published we showed an vivo proof of concept and in an animal model we were the first group to do that and then contextualizing that with one of the current cornerstones of standard of care sglt2 and so what we showed was that not only were able to reduce proteinuria to demonstrate that proof of concept we actually in that model did it better than the sglt2 and importantly in combination, we basically got the levels back to normal. So we published that, and that was encouraging. So we had the genetics, we had the preclinical data, and then last year, what we did in terms of the clinical data, now we knew that all approved kidney disease agents had this phenomena where they showed an initial, what's called an initial EGFR dip, which is a little counterintuitive because you actually want your EGFR to improve over time, but all agents that have been approved for kidney disease, including ACE-ARBS, SHLT2, even Carindia, they show this initial EGFR dip, but it plateaus and flattens out relative to the placebo such that you actually have renal protection over time. So that was interesting, and it was in the literature that you could see this even in healthy volunteers. So we knew that, and if we had this hypothesis of genetics, as well as from the preclinical data, we said, let's look for that EGFR dip in the healthy volunteers. And we saw that. So we published that last year, which was not only did we see that in a dose response manner, we also saw that when we pulled off the patients on treatment, their EGFR bounced back, inferring that the effect is due to the treatment, not just by chance. And the other thing that we saw is it's in the range of the EGFR dip. That's in the same range as SGLT2 that's been previously republished. So that all was very notable and interesting to us. And so that helped us better understand we could have a hemodynamic effect. And so our current understanding of the mechanism of, I would say, SLC in the context of kidney disease, one is it could have a hemodynamic effect, which we've seen now in the clinic. The second thing is that we know that it's a solute transporter and not just a neutral amino acids like phenylalanine, which we talked about for PKU. but it also manages these toxic metabolites which in excess can be damaging in the kidney so the fact if you can inhibit it you might be able to just get rid of these toxic metabolites by just excreting it out into the urine similar to what we do in PKU so not only could you have the benefit of an SGLT2 like mechanism with the hemodynamic effect but you might also be able to just have a complementary or second type of mechanism by just getting rid of these toxic metabolites. So the idea here is that in the clinic, what we might be able to do in kidney disease patients who are not necessarily responding to standard of care, in a proof-of-concept study, we would just look for UACR reduction in those patients that haven't been responding to things like an ACE-ARB or maybe an SGLT2, and if we see, again, a 30% reduction in UACR, that would be proof of concept. Because not only now that we have Wanda Genetics, the in vivo proof of concept, the proof of mechanism in healthy volunteers, but if we can show UACR reduction in patients who haven't been responding to standard of care, that would be the first time anyone has demonstrated this with SOC 6A19.

Elizabeth Webster, Analyst — Goldman Sachs

Great. In the last few minutes here, Just on the financial aspect, just remind us of your cash position and your cash runway.

Jason Coloma, CEO

So, yeah, we just reported with a recent raise, we had a little over $528 million. That funds multiple catalysts that have been described today. So not only does it complete the Horizon Study, which we'll have the data later this year, early next, the PKU Proof-of-Concept Study, the CKD Proof-of-Concept Study, and allows us to even initiate the pivotal study for 829 in kidney disease.

Elizabeth Webster, Analyst — Goldman Sachs

And just in CKD, when can we expect that next data set?

Jason Coloma, CEO

Oh, we said we would start the study first half of 27. We haven't announced when the catalyst would come from that. But, you know, you can see multiple catalysts, again, from our April 1 program as well as our PKU program. And the cash runway guidance that we have through that that I just gave you

Elizabeth Webster, Analyst — Goldman Sachs

this into 2029 thank you so much yeah thanks for being with us really appreciate it