$ProKidney(PROK)$ HCW CEO访谈
说话人1 00:03
Hello, everyone. And welcome to the ac we invite 4th annual kidney conference. My name is london. I'm a senior research associate at the firm. Here with me is bruce skeleton, ceo of pro kitty. Hi, bruce. Thanks for joining us.
说话人2 00:17
Thank you, linda. So it's great to be here.
说话人1 00:20
So maybe bruce for those who may not be familiar with pro kidneys, would you please provide a brief overview of the company and how you're approaching chronic kidney disease, ckd.
说话人2 00:31
yeah, absolutely. So lender, we're pre commercial autologous cell therapy company. We have a single asset being tested in patients with advanced chronic kidney disease and type two diabetes. We went public in 2022. That was on the background of about 10 years of preclinical and early stage clinical research. We have offices in boston rally and winston salem in north carolina. The winston salem location is where we do our manufacturing. In many ways, we're a different company today than what we were in 2022. When the company went public, we now have close to 250 employees. And these employees have really driven an enormous amount of progress over the last 18 months. Just quickly, some of those big highlights, we resolved a lot of their quality audit, all of our quality audit findings. After we put a manufacturing pause in place at the end of 2023, we restarted our phase three clinical study about this time last year after a protocol amendment. We've had too late breaking phase two clinical trial presentations at scientific congresses. We've changed our regulatory strategy, allowing us to seek approval on just one singular phase three study. And then last week, it just so happens. We also released top line efficacy and safety data from a phase to another phase to study called regen 007.
说话人1 02:10
Yeah, perfect. That's very helpful. So I think it's important to contextualize a little bit ckd what's the current therapeutic options for ckd patients and what's broken this target population?
说话人2 02:23
Yeah, so today, maybe i'll just start by saying, I think we're living in a golden era of new therapeutics and chronic disease, right? For patients with diabetes and ckd in particular, there are four pillars of care, render and your tension system blockade with either ace inhibitors, a a or bs, sglt two inhibitors, non throttle, mr as well as gop one receptor agonists.
说话人2 02:52
So these landmark clinical studies, I every year there seems to be a line a new landmark clinical study, but those using sglt two inhibitors and gop one agonists focused largely on patients with less severe kidney disease. Primarily stage two and stage three. We find ourselves in a very unique situation where we think our product is most suitable, or parent cells are products named, are most suitable for patients with even more advanced kidney disease where there's less data. We're focused on primarily stage three b and stage four chronic kidney disease.
说话人1 03:30
Perfect. And as you mentioned, you're focused on more advanced security patients. Where do you see with parents of feeling into the current treatment landscape with sut two inhibitors and gnp one therapies?
说话人2 03:43
We hope. And honestly, I expect that as time goes on, there's gonna be even better utilization of sglt two inhibitors, as well as gop one receptor agonists for patients with diabetes and chronic kidney disease. But we also know that these therapeutics are not cures. And even within the control setting of randomized controlled trials, many of these patients lose kidney function and continue to develop kidney failure. We see real parent cell as a real option for those patients that continue to progress. Thats a real issue and continue to need dialysis at some point in time as well. So we see ourselves as that potential option to keep patients off dialysis.
说话人1 04:33
Awesome. And moving into the technology itself, you already described a little bit. What will rsl is? But could you please elaborate a little bit more on the procedure itself from tissue acquisition to the injection process?
说话人2 04:46
So lander, we under intervention radiologist, under the prescription of an nephrologist, the ir typically takes a kidney biopsy, and we've trained the irs to take the biopsy primarily from the kidney cortex. It's mainly done under ct guidance, so it can also be done under ultrasound. That biopsy is then shipped to a manufacturing site in winston salem. When the biopsy arrives, it has somewhere between 50 to 100,000 cells within the biopsy. And then over the course of the manufacturing process, we select out a certain type of cells, mainly tubular epithelial. And the end product ends up being 2 to 3 billion cells. And we then dose the patient based upon the size of their kidney. Bigger kidney gets more cells, a smaller kidney gets less cells. The typical injection, which is also done by an intervention radiologist. Under ct guidance. The typical dose in one kidney is somewhere between 250 and 500 million cells. The first dose is typically given in the same kidney that was biopsy. The second dose is given 3 months later in the other kidney,
说话人1 06:09
and maybe going more into the mechanism of action. Are you at the american society of nephrology meeting last year to present the data storing require themselves? Mechanism of faction. What should we expect from the next mechanistic update in the second half of 2025? And how will this build upon prior findings?
说话人2 06:30
So ii will start by saying, I don't think we still have work to do on our moa right? Got older data, which suggests that its impact, this primarily through fibrosis, anti inflammation, but we still have some work to do using more than more up to date techniques to demonstrate moa where what we did at last year's asn we focus primarily on characterizing real parent cell and the changes that occur from the biopsy until the final product.
说话人2 07:05
This year, we've submitted abstracts that characterize role parent cell and the secret home. During cell manufacturing, we describe cytokine, gene, expression, and metabolic reprogramming that gives us even more insights into the moa and just as a teaser, we have a very unique new model to test moa that hoping it gets presented at asn we don't know. But if it does, I think many people will find it extremely interesting in how we're thinking about proving what the moa is.
说话人1 07:41
Also, that's exciting. So maybe before we jump into the pivotal trial that's ongoing. Last week, as you said, you announced positive top line results from the 007 study. Congratulations, by the way. Can you walk us through the study design, the key findings and how these results may provide read through into the ongoing phase? We pro act one trial.
说话人2 08:04
Our lender, we were excited about last week's announcement, too. We didn't expect the the result that we received, at least the market result that we received, but we were pretty excited about the results when we first had a look at them.
说话人2 08:21
Region 007 was a multicenter us based phase two open label study. Patients were randomized into two arms. And those two arms were, if I should say that the patients were diabetic and had chronic kidney disease with the gfr between 20 and 50, the two arms that patients were randomized to one was group one.
说话人2 08:46
Group one is really important for our phase three insights into our phase three program, because group one had the same dosing schedule that we're using for ongoing phase three program. Patients received two scheduled injections, one in each kidney, approximately 3 months apart. We think in that because of the dosing schedule, we think that's the most insightful data. As part of the 07 readout. Group two tested an exploratory dosing regimen in which a patient received one dose, but only and received only a second dose based upon biological triggers, such as a change in egfr or an increase in urine albumin loss. And that second dose for those patients who ended up getting a second dose, was, on average, 10 or 11 months after the first dose. So very different than how we're executing our phase three trial at this point in time. The pre specified endpoint, the primary efficacy endpoint was the difference in annual slope, in egfr in the 2 year pre injection period, versus the period after the last repair insult injection. And patients had an approximate follow up of 18 months after the last injection in both groups. Quickly, we randomized 53 patients, 49 of them ended up getting treatment. They were part of the modified intent to treat readout that we provided. In group one. Again, that's the important group, providing us a window into what phase three may look like. Their annual decline in egypt for a slope before treatment was 78 %, and they declined annually at - 5 . 8 m ls per minute. The 78 % refers to the difference from the pre injection to the post injection. And post injection, the annual decline was - 1 . 3. So from - 5 . 8 to - 1 . 378 % improvement in the decline of kidney function, this difference of 4 . 6 is what we were surprised with that exceeded our expectations. It was statistically significant, but more importantly, clinically meaningful. And as a reminder, the benefit observed in some of the other landmark papers is typically between one and two m ls per minute per year. Maybe sometimes a little bit more than two, but we observe 4 . 6 smaller population. But still, this was something that we were exceeded our expectations. Importantly, of that group one, 24 patients, 15 of them also met our phase three inclusion criteria. And those patients had similar results as the entire group one. Again, making some suggestion, perhaps, of what benefit we might see in phase three.
说话人1 11:58
Get paid. Yeah, go ahead, please.
说话人2 12:03
Just quickly in group two, we also saw a benefit in group two. The benefit was not as great, but it certainly suggested that there was a dose response. But it also confirmed to us that we're on the right track in dosing patients with two injections, one injection in each kidney.
说话人1 12:20
Perfect. And you besides the results, you also announced that you're planning on submitting the full 00, seven data sent to the american society of nephrology meeting. What additional information should we expect during the kidney week in november.
说话人2 12:36
All we released this week was the safety results, the primary top line safety, which was consistent with the safety events we see with the kidney biopsy, as well as the primary efficacy. So a full kidney week, you everyone will see get a better understanding of the patient characteristics at randomization. What happens to the slope over time? So you expect to see a figure with confidence intervals around those pre slopes and post slopes. You can also expect to see some subgroup analyses we've been asked, because we have type one diabetic patients in the study. Was there a difference in type one versus type two diabetes patients? Was there a difference in patients? Older versus younger? More albumin, urea, less albumin area, sglt use or no sglt to use so lots of other sort of just a deeper dive in the data that we anticipate being able to share in november perfect.
说话人1 13:31
That makes sense. Based on the 007 results. I'm just curious to know what your thoughts are in terms of a stabilization versus improvement. Would you consider stabilization already a significant clinical benefit for these patients?
说话人2 13:47
First, i'll say, iii I don't think we're generating new nephron, so I don't think that's how repair and so works.
说话人2 13:55
I don't think we're gonna get an improvement in kidney function, lots of variability, but I don't think we'll get a consistent improvement. What we are seeing is very close to a stabilization or preservation kidney function. The - 1 . 3 annualized change that we saw in the treated patients in group one. That's very similar. What you'd expect to see in an older adult as part of normal aging. We do think we're seeing and this was consistent with prior reports from us as well. So we think we're seeing just a preservation or stabilization of kidney function, which is very meaningful for patients.
说话人1 14:30
Perfect. So maybe diving into the ongoing phase three provide one trial. Could you guide us through the general study design? I know that this time we have a sham control group and remind us a little bit about the end points.
说话人2 14:44
So the key entry criteria type two diabetes and chronic kidney disease. In essence, we're looking at patients who got agfr between 20 and 35. Eligible patients are randomized to receiving real parent cell or a sham. And that sham includes a sham biopsy and sham injections, all done in international radio biology suite. The treatment. If you end up getting your parent cell, you get a biopsy. It will parent cell 3 months later in the second injection 3 months later. We do follow both patients over time. The study was designed.
说话人2 15:25
For a time. It was a time to event study. It still is a time to event study. And the events are at least a 40 % reduction of egfr on egfr less than 15 for more than 30 days or crying, dialysis, or transplant, or death from kidney or cardiovascular causes. It's a composite endpoint right now. It's designed to roll over 600 patients. But again, that's driven by how fast events may happen. And obviously, the longer we follow patients, the more likely we're expected to see the desired number of events.
说话人1 16:03
Perfect. And in terms of results, do you expect concoming and use of sglt one inhibitors or glt one receptor agonist to enhance the therapeutic effect of real parent cell?
说话人2 16:15
Two things what we've stratified randomization by sglt two inhibitor use at baseline. We think that's more important. And gop one agonist, for example, lot reasons I can get into later if we needed to, but that was the stratification that we decided to use. We also believe the mechanism of action is different. We don't see decrease in albumin, urea with repair and cell. We don't think it has an intracellular hemodynamic effect. We think it works differently than sglt twos or gop ones, for example. And for that reason, we think the effect may be additive. We don't think it's synergistic. We have no Information to say it's synergistic, but it's probably additive if we demonstrated benefit.
说话人1 17:03
Perfect. So what's the current enrollment status of the trial? And what's the feedback that you're getting from investigators at the clinical sites?
说话人2 17:12
We haven't provided any guidance, broadly speaking, on our moment status at this point, but I anticipate will provide some updates towards the end of this year or maybe early in the 2026, particularly as it relates to potential accelerated approval with regards to our investigators and others that work at the sites.
说话人2 17:33
I'd say we've got some very, very engaged sites, some very interested investigators. We consistently hear support on the population of patients we've chosen to study, because these are under studied population, as well as the innovation that we're bringing to the space. I i've gone on some tours to meet. Investigators have presented some of our moa data, some of our phase two data, even the radiologists that show up, tend to get very excited and interested in what we're doing.
说话人1 18:10
Perfect. And to the extent that you can share in terms of regulatory dialogues with the FDA a Taipei meeting is scheduled for this summer to discuss potential accelerated approval pathway for repair and sell. What would a successful outcome of that meeting look like for you? And do you spend your current cash balance to fund operations up to the phase three readout?
说话人2 18:32
Yeah, so a successful meeting for us would be confirmation from the FDA that egfr slope can be used as the surrogate endpoint for accelerated approval. Number one, number two, confirmation that are estimated treatment effect. Our assumptions essentially is clinically meaningful within the framework of an accelerated approval pathway. And number three, confirmation that our study population that we intend to use for accelerated approval is acceptable. This would provide us a timeline for when we'd expect accelerated approval readout. And that timeline, we hope, will come before we run out of cash for operations. And we think will currently we have 320 as of may, $328 million that takes us into q two, twenty, 2007 to fund our operations.
说话人1 19:26
Perfect, awesome. So as you look forward to our potential commercialization, where do you stand in terms of manufacturing, readiness and scalable production capacity for the product?
说话人2 19:38
Our manufacturing, it is gonna be done in Winston Salem. We've got capacity to produce product for a phase three patients. We also have capacity for our initial commercial launch and what we expect is demand at launch. We also have started expanding our facilities in Winston Salem, and we will build additional capacity, almost like in a modular fashion, as we expect, men to grow over time.
说话人1 20:03
Okay, perfect. So and currently, PRO act is primarily focused on the us how do you envision the potential expansion of repentance into additional territories in the future?
说话人2 20:14
We know there's lots of patients outside the us that could also benefit from a parent cell. So we're not going to ignore those countries outside of the us but right now our focus is on execution and getting to market in the us. Always open for opportunities that might come our way from potential partners who might be interested in looking at countries outside the us.
说话人1 20:36
amazing. So for the sake of time, Bruce, would you like to summarize the upcoming catalysts for the next 12 months? Or the current fast position relative to this catalyst or clarify anything that investors should be aware of?
说话人2 20:49
I think I covered most things. Obviously, we're pretty excited with the phase two data. We will give an update on our type bfda meeting very, very soon. And then we touched upon this kidney week is an important time for us, not just the moa but also full results. Hopefully we'll get a late break in clinical trial presentation. I think we will. And we'll be able to talk more all soon about what the data showed.
说话人1 21:17
Perfect. So thanks again, Bruce. This was highly informative, and we look forward to upcoming updates. Great. Thank.
说话人2 21:23
you. Lender. Appreciate it.
说话人1 21:25
Thanks.