Good morning, everyone. My name is Yatin Suneja, one of the biotech analysts here at Guggenheim. Welcome to our SMID Cap Biotech Conference. It is my pleasure to welcome our next presenting company, SAB Biotherapeutics. From the company, we have a few executives here, but I'm gonna be having a chat with the Chairman and CEO, Sam Reich. Sam, why don't you maybe spend five minutes, just tell us the story of SAB? What are you doing? What are some of the key milestones? Then we'll go into the Q&A. Obviously, you presented some recent data. I'm gonna sort of go a little bit deeper there just to understand it, but just, you know, maybe sort of make some opening comments.
Sure. SAB Bio is a clinical stage biotech company with an anti-thymocyte globulin asset, which just finished phase I. Our proprietary platform allows us to make specifically targeted human IgG products, plasma-derived products. Absent SAB, products can either be human IgG from human plasma, which do not have a specific target, or they can be from animal and be foreign protein, and they have safety issues. What we're doing at SAB is we're focusing on autoimmunity, making a human anti-thymocyte globulin because there's a rabbit anti-thymocyte globulin that is very effective, specifically in T1D that has safety limitations and the inability to redose because it's foreign, whereas we can make a human one. Focused in type 1 diabetes and in general autoimmunity.
Got it. Very good. Just walk us through this, you know, Tc Bovine platform, right? Like, is this something unique that you have? Has anything been done using a similar technology by somebody else? What is proprietary here, and what are some of the benefits of this platform?
The platform we have was developed in-house. It's wholly owned. It's not subject to any licenses or royalties, and it is a transchromosomic cow. The cow has a lot of significant genetic engineering in that it does not make its own IgG.
Mm-hmm.
It makes human IgG, which comes off a human artificial chromosome. That allows us to have an animal that we can house and feed and vaccinate to stimulate its immune system to create antibodies towards the target, and then derive a purified product from the plasma, which is human. We can make specifically targeted human IgG in our platform. We're the only company, we're the only company in the world that has this platform, certainly a world leader in cloning and genetic engineering.
Got it. How do you achieve this high level of specificity? Are you doing specific, the specific way you immunize these cows?
Yes. With, by vaccinating the cows, we make an antigen, essentially vaccine, although it does not have to be an approved human vaccine because these are animals. By hyper-vaccinating the cows or giving them repeat vaccinations with that antigen, which is, you know, the desired target or a combination of the desired targets, the cow's IgG is enriched for the target.
The advantage of using cow versus other species is, number one, volume. What else? Like, is there safety benefit there? They're less immunogenic? Like, what is the key, like, two or three advantages?
There's probably three key features that make the cow, sort of the ideal species for this. One is that it's a ruminant, and ruminants, since they're, you know, grazing, grazing animals, they have very robust, it's a known fact, it's a known common knowledge that they have very robust immune systems. So when they're vaccinated, they have very high titers, significantly higher than humans and other types of animals. So ruminant is one. Two is size.
Mm-hmm.
They're large mammals, so they produce a lot of plasma. For a plasma donation from a cow creates 60 times as much plasma as a plasma donation from a human. You can kind of imagine, and between goats are smaller than humans, you can get less from a goat. This, the ruminant, this fact that it's large, and then the fact that from the dairy industry, all the technology, know-how, infrastructure for housing, feeding, maintaining, all exists. Our cows are housed just like a dairy farm.
Yeah.
You know, they're mild-mannered. Those are the three key features.
Okay. All right. Could you now review for me some of the clinical data that you have generated very recently, like a couple of weeks ago when you had the call and the R&D Day? Just walk us through what you have learned, what have you generated, what type of doses you have used, and what is the future path?
Sure. To start, the basis of our program is that a rabbit anti-thymocyte globulin called Thymoglobulin is very effective, perhaps the most effective for preserving C-peptide, which is beta cell mass, and is the goal in newly diagnosed type 1 diabetes patients. We have this known mechanism that's known to be effective. Because it's a rabbit protein, it's immunogenic and causes serum sickness, which means, one, the patients get sick, which is just not acceptable for commercial use, and two, it cannot be redosed. The goal of our trial was to show that we have that mechanism of action that drives efficacy in type 1 diabetes, and we do not have serum sickness, and we do not have immunogenicity that leads to anti-drug antibodies.
In this trial, phase I is a single ascending dose in healthy volunteers where we started at 0.03 mg per kg, and in five cohorts escalated to 2.5 mg per kg. One single course, one administration, is given over two days to get that full dose. We looked at serum sickness, which is a clinical presentation. We have a very highly sensitive, validated assay for anti-drug antibodies. We also looked at a panel of T-cell markers, which indicate the type of T-cell or the state that the T-cell is in. What we showed was that we activated the T-cells in such a way that led to exhaustion signals that were durable.
After a single dose, exhaustion signals on CD4 and CD8 cells that were durable, which is the signature mechanism of action that drives efficacy with Thymoglobulin, as well as a Treg sparing effect. What drives efficacy in Thymoglobulin is inducing T-cell exhaustion and sparing Tregs. Tregs are key for having a healthy immune system that's not attacking self. That combination of effects is what's known to drive efficacy with Thymoglobulin, and we showed that we do indeed have that same mechanism of action without the limiting serum sickness and with the ability to redose.
Got it. So you could redose, no serum sickness. What about, like, lympho depletion? Is that something of an issue with, you know, your program or the RATGs that we see rabbit, thymoglobulin?
Yeah. Our thymoglobulin does lympho deplete, which would cause a concern with the regulators for safety for long-term use in a wide population, but also pediatric and adolescent population, whereas ours does not lympho deplete. What is exhibited by our drug? Let's start with thymoglobulin.
Yeah.
Thymoglobulin starts with a profound lymphopenia, which then does not recover, and patients have a long period where they are lympho depleted, which is a problem from the regulators for safety for a chronic use product.
Yeah.
Our product, which is key to the, another difference being rabbit or foreign and human, does cause that rapid and profound lymphopenia, but it is not lympho deplete by three days. Lymphocyte levels are back to normal, which is, has to do with Fc receptors for human versus rabbit. That initial profound lympho depletion has activated those T-cells, and they've changed states, which is change to an exhausted state with no long-term lympho depletion, which is much better for safety and regulatory path.
Got it. And, and how, like, I mean, there is this lympho depletion, like, what level of lympho depletion you get, does it cause any clinical significance, or has that been an issue with you so far in the phase I study?
We don't have lympho. You mean the initial,
The initial, the transition.
Lympho penia.
The transition.
Yeah. The lymphopenia, upon infusion, which is also called an infusion-related AE.
Yeah.
Is significant.
Mm-hmm.
That is an indication of on-target activity, desired pharmacologic effect. It is not a clinical AE in that the patient does not have a symptom. It is a lab finding.
I see.
In the community of doctors that treat these patients and the patients themselves, it is not a concern. In fact, it was expected and desired.
Got it. What doses have you used so far, and what is the plan? Do you plan to go higher on the dose, or you sort of have figured out the dose and where, what that dose is?
We have gone, the two higher doses, which are the most relevant, are 1.5 mg per kg and 2.5 mg per kg. It's likely, when all the data's collected and all's analyzed, it's likely that one or two or both of those doses will be continued for study 'cause we do see that, market mechanism of action. I would say it's probably unlikely that we'll have a need to explore higher doses, but it's certainly,
Got it.
theoretic possibility.
Got it. Got it. Should we, so I think there is some data on this RATG, right, at the 2.5 milligram dose in type 2 patient. I mean, you do not show any serum sickness. Is there a reason that you have to go up, or 2.5 is sort of, is where we think should be the max?
Right now, we're seeing everything we wanna see.
In that range.
In those higher cohorts.
Okay.
I think we're satisfied.
Okay. Could you maybe talk a little bit more about these biomarker data that you have generated, some of the CD4, CD8 positive T-cell exhaustion, whether that, that's that or other data, just to put in perspective the relevance of those?
I'll start with the most known quantity and the one I'm most able to speak to.
Yeah.
Which is PD-1. PD-1 positive, CD4 or CD8 cells is the key marker of exhaustion, and that's also the marker that was used with both Tzield and Thymoglobulin to look for exhaustion. That's probably the most well-understood and most clear marker. Although we have looked at a panel, including TIGIT, PD-1 is sort of the hallmark data that we replicated from what we saw with Thymoglobulin.
Okay. Okay. How far have you looked? Have you looked beyond day 120, or have you gone to day 120?
we've only, so there may be some data at 180 that hasn't come in yet, but it was 120 day was our final.
analysis for the full panel, and we have seen all the data up through 120 with all the cohorts.
Okay. Are you seeing any difference between the human, not humans, healthy volunteers and patients, because there are these some type 1 patients that you have dosed?
We have, well, if we've dosed any type 1 patients, I don't know about it, but it is in the works.
In the works.
There may have been patients dosed, and it hasn't gotten to me yet 'cause it is in the works.
Okay.
The immune system of the healthy volunteer is a pristine sort of landscape for looking at changes in immunity, and that really gives us the most information. While looking in T1D patients is relevant because we're going into 140 plus T1D patients, we wanted to have that really for safety and for the regulatory purposes.
Yeah.
We do not expect to gain any new information from that.
Got it. I'm gonna discuss the SAFEGUARD study, but, like, what in general is the, is the plan? Is type 1 diabetes is where you will go, or could you potentially cover, consider something like a transplant as well?
The SAFEGUARD study is in type 1 diabetes.
Yeah, that we'll discuss.
Yeah. Yeah. That's newly diagnosed, type 1 diabetes patients. The most, the very next indication will be, at-risk diabetes patients, which we call also Stage 2. We have Stage 3, which is what we call early intervention, what Sanofi calls early intervention.
Mm-hmm.
Stage two is delay onset. Those are, that's our sort of primary focus right now. Although there is data conducted by academia using Thymoglobulin and other indications as well, Thymoglobulin is used commercially for organ transplant. Of specific interest is unmet needs where the rabbit won't be acceptable, won't be considered, and where there's good data and evidence and excitement in the research community, and that would include scleroderma, lupus nephritis, and celiac.
Interesting. Those two.
All good data there supporting use of Thymoglobulin where a rabbit product won't be appropriate for the, that patient population.
Got it. Got it. Okay. All right. Let's talk about this phase II SAFEGUARD study. I think you've said that you're gonna start in, in the middle of this year. What is this study? How many patient? What type of patient, you're trying to enroll?
It is a statistically powered study to look at preservation of C-peptide at one year in patients that are newly diagnosed with type 1 diabetes, and that would be within 100 days of diagnosis with a certain amount of C-peptide. They'll be given two active groups and one placebo group. The two active groups have not been decided yet, but you could imagine one would be 2.5 mg per kg.
Yeah.
The key measure is C-peptide at one year. The patients will be stratified so that we will get adults, adolescents, and pediatric patients and have that whole age range, which I think is 5 to 40.
So and.
We will also look at clinical endpoints, most notably time in range, which now that continuous glucose monitors are standard practice or at least very common. We can have an inclusion criteria be that all the patients in the study wear continuous glucose monitors. We can collect the data of how much time they are in the normal glucose range, which is a meaningful clinical endpoint.
Yeah. Yeah. For this study, do you anticipate a similar transient lympho depletion, you know, on day one to three that you observe in healthy volunteer?
Yeah.
Okay. And what about the, you know, the T-cell exhaustion? Is all of that data being collected? Like, what can, what do you expect there? Similar data?
We would hope it would be the same.
It'll be the.
Yeah.
Same as healthy volunteer. Does this study design consider a potential of redosing? Are you thinking of redosing, or is it just single dose?
We plan to redose. I don't know that it'll be a part of the primary efficacy endpoint that drives the study or not yet, but there will be the opportunity to redose, and studying redosing in the next year. We'll start talking about.
So far, you have not redosed, right, or have you?
We have not yet redosed.
I based on the, you know, the lack of immunogenicity and all, you do not anticipate an issue with redosing?
Not an issue for two reasons. The first reason is that human IgG is redosed chronically.
Yeah.
for 30 plus years, and our product is human IgG. The second is that we proved empirically with the data from our phase I.
Mm-hmm.
That our product is human IgG. There's no immunogenicity. There's no ADA.
Mm-hmm.
We have every confidence that we can redose this product.
Got it. Got it. To the best of your understanding, when you put out these data, is there something that you think, like, we do not understand or we need to sort of spend more time understanding it? I am just curious about the dynamic of the data and why I think broader investor community did not sort of understand it when it was presented.
I think.
What the disconnect might be.
I think that there's often an expectation that there's gonna be some efficacy endpoint with the P-value. Understanding mechanistic data from a phase I takes a lot of thought, research, sort of homework in advance so that the community, whether it's experts or institutional investors that have taken the time to understand.
Mm-hmm.
The molecular mechanism that drives autoimmunity or drives efficacy in type 1 diabetes, get the data and understand exactly what it is. A community that's just looking for a P-value and an efficacy endpoint, maybe their expectations were not managed well.
Yeah.
They just didn't see that and were confused or disappointed.
Yeah. How has the physician feedback been, since you presented the data? Have you shared it with broader in, KOL community or the initial KOL? Like, what is their feedback? What are, like, one or two things that they really like about the product?
The KOL feedback, KOL feedback is excellent. We have, on our website, you can see the list of our clinical advisors. We've shared it with just collaborators that aren't our clinical advisors, and these are people that have worked on Tzield, worked on Thymoglobulin, have studied and written papers on the mechanism of action. They're thrilled.
Mm-hmm.
that we preserve Tregs. They're positively surprised that we don't lympho deplete. They're also very excited, and the quote has been, "You're in a different league now," that we induce exhaustion in both CD4 and CD8.
Yeah.
Because CD8 exhaustion is the hallmark of Tzield, and CD4 exhaustion is the hallmark of Thymoglobulin, and we, we have both.
Got it. One question on the lympho depletion. Obviously, yours is a transient one, and then if you look at the RATG, it's more, I would not say permanent, but it's more longer, right? Do we know at what time point they start getting, the cells back, if you have?
It's not for two years.
Two years. Wow.
Yeah.
Okay. Two years. Okay. Final question for me. So the SAFEGUARD 2 study is gonna start in the middle of this year. When should we anticipate data? Are there interim updates that we should expect, or we'll get data once the full study is, once you enroll the full study?
There'll be some news in a year from trial start around an interim analysis. That'll be limited in order to maintain blinding and, you know, maintain the power. We're on track to have top-line data and, you know, the most important data, in mid-2027.
Yeah. What and what is the earliest time point that you would expect the C-peptide is, the changes in C-peptide level?
From what we know from Tzield and Thymoglobulin, you can start to see placebo separate from active by three months, but you don't start to have, like, static separation until a year. There are.
I see.
Academics that can model out from six months and tell you whether it's gonna work in 12 months, but that's not, you know, regulatory.
For your in, if you do an interim, I mean, I'm fair to assume it'll be at least three months?
There'll be all ranges depending on the patient, and it'll be a statistical model to determine whether or not to drop one of the arms.
Okay.
Or whether we can stop for efficacy.
Okay. I think I missed the number. How many patients you said across the arms?
142.
142. That's a pretty decent-sized study.
Mm-hmm.
All right. So data most likely next year then, some interim. Very good. I think those were almost all the questions I had.