All right. We can get started. Good day, everybody. My name is Ashwani Verma . I cover SAB Biotherapeutics, Inspect Pharma. Welcome to UBS Global Healthcare Conference. With us, we have SAB Biotherapeutics. Really excited to have Sam Reich, who is the CEO, and Lucy To, who is the Chief Financial Officer. Thank you so much for joining us today.
Thank you for having us.
Maybe, like, it'll be good, just for the benefit of the audience, just if you can give a quick background about the platform, and then we can get into more, more specific questions from there.
Sure. SAB is developing a drug for type 1 diabetes to preserve beta cells or preserve the organ that is being damaged by the autoimmune condition. It is made with a platform that is wholly owned, which is a trans-chromosomic bovine, a cow that makes human IgG. We know that anti-thymocyte immunoglobulin is very effective in type 1 diabetes for preserving beta cells, preserving C-peptide, from a drug called Thymoglobulin, which is made by Sanofi and has been extensively tested in type 1 diabetes patients with excellent results. Including most recently, on September 18th, it was published in Lancet a new clinical trial showing that this anti-thymocyte globulin made by Sanofi called Thymoglobulin was effective in preserving C-peptide and reducing HbA1c or improving glycemic control. The issue with Thymoglobulin is it is the rabbit. It is very toxic. It makes the patient sick.
In fact, Sanofi is not even developing it for type 1 diabetes because that safety profile is not acceptable for this patient population. With our platform, we're able to make a human version of Thymoglobulin with human IgG that targets thymocytes or T-cells. And it's called SAB-142. It's going into the clinics now for a phase 2b, which is pivotal. And it's the human version of a drug that we already know is very efficacious. We have high confidence that we'll be able to replicate those results and have a successful drug. We have also proven in phase one that the drug has the safety attributes that we believed it would have, which are safety advantages when compared to Thymoglobulin, that the drug does not make the patient sick, it doesn't cause serum sickness, and it's not immunogenic. It can be redosed.
Great. Maybe, just, like, when you mentioned Sanofi, they have the TZIELD, as well. Is it effectively going after the same indication that you're pursuing, or is that a slightly different setting in any way?
It's two parts. First, Prevention developed TZIELD, which is a monoclonal antibody against T-cells, the same target as ours, in type 1 diabetes. Sanofi bought Prevention for $3 billion in 2023. The initial indication that TZIELD was approved for is stage 2, or delaying progression to stage three. Stage three is type 1 diabetes as you know it. Stage two is kind of like prediabetes. That's not our initial indication. Our initial indication is stage three, which is the lion's share of the market. That's clinical type 1 diabetes. That's what you think of when you think of type 1 diabetes. Now, TZIELD is about to get a decision on stage three.
Right.
We will eventually go after stage two. We expected TZIELD to be approved in stage three. Our phase 2b that we're starting now called the Safeguard trial is in stage three. We will also go after stage two. We will compete with TZIELD. We believe we'll be best in class, and all the data supports that.
Great. Yeah. Awesome. Maybe, just if, if we talk a little bit about the data that we have seen from the phase one study that you showed, like, earlier in the year, I think, the preservation of Tregs at the SABO levels, and there is, like, a CD4 exhaustion increase that you showed. If you can highlight that a little bit, like, just what are the key takeaways from that data?
Sure. We start with the background that Thymoglobulin, this rabbit anti-thymocyte immunoglobulin, is effective at preserving beta cells and reducing A1C. The mechanism that Thymoglobulin has is exhausting T-cells, leading to durable T-cell exhaustion while preserving Tregs. The objective of our phase one was to show that we do not have the safety issues that Thymoglobulin has while we do have the mechanism, which is durable exhaustion of T-cells while preserving Tregs. That is what we showed. We showed in our phase one that the drug does not cause serum sickness, it is not immunogenic, which means anti-drug antibodies are not generated, and we can safely redose, and that our drug induces durable T-cell exhaustion while preserving Tregs.
Got it. And how does the magnitude of CD4 exhaustion compare to that of, like, rabbit IgG?
It's comparable. Similar.
Got it. Okay. Like, does that mean that you need to, like, it essentially generate, or it can generate more meaningful efficacy in type 1 diabetes? Is that a fair assumption based on the data?
Based on our data and all the data published from Thymoglobulin, we expect to have similar efficacy as Thymoglobulin. The Thymoglobulin is remarkably efficacious. It's the best agent tested so far in type 1 diabetes as the best results, which is meaningful preservation of C-peptide, reduction in HbA1c, or improved glycemic control, at one year after a single dose, which is superior to TZIELD.
Yeah. And then in terms of, like, the safety parameters, so yeah, just so far the data that we've seen, like, the lympho depletion that we've seen in roughly 80% of the patients, can you talk about that? Is this essentially, like, severe, like, threatening? Like, how does that,
Yeah. So in the phase one, we reported that the majority of patients have a profound lymphopenia after getting the drug. The doctors and the FDA, no one is concerned about that. It's transient. It resolves within a day after the dose. It's just a lab finding. It's not clinical, so there's no clinical symptomology. The patients don't know it. It shows up on the lab finding. It's evidence of the drug working. It's on-target activity of the drug, and it is transient. What it does, it's a sign that the drug is working.
Mm-hmm.
There are no symptoms, and it resolves immediately.
Right.
Within a day.
It, so there's no, like, additional, you know, therapeutic intervention that is required? It's self-resolving?
There's no therapeutic intervention.
Okay.
It's not, there's no clinical presentation. The patients don't know. It's a lab finding.
Is it possible, like, as you sort of run, like, a bigger study, more diverse patient population, that you can see, like, more severe level of AE? Or do you think that the phase one data kind of convincingly proves that this is a transient, short-term condition?
Oh, yeah. It's, it's totally established that it's transient.
Okay.
It's something seen with T-cell engaging therapies. So it's what.
Yeah.
The doctors are used to. And while it may sort of look remarkable when you see it presented as an AE that there's this lymphopenia in 100% of the patients, it's when you say 80, if they're on active, it's 100%.
Right.
They're in an active dose, but it's not something that is of a concern to any of the docs or the FDA. It's an on-target activity that we expect to see, and it's not remarkable from a clinical perspective.
Yeah. Okay.
I'd also add that lymphopenia is also seen in TZIELD, in the drug arm as well. It's also transient. It's a sign of on-target effect, but on TZIELD, it takes longer to resolve.
Right.
We essentially have the same profile, but ours resolves quicker.
Great. Yeah. And then, just looking at the phase two, this Safeguard study, so roughly, like, the, you know, the choice of the population that you went after and the trial design, like, if you can elaborate on that, what you.
Sure.
Maybe go down that path.
The target product profile is to preserve beta cells in newly diagnosed type 1 diabetes patients. There are 65,000 new diagnoses every year in the US alone, patients that desperately want a therapy. Today, there's nothing. The patients that are included in this trial are newly diagnosed patients. They'll be patients who have received a diagnosis of type 1 diabetes within 100 days that have a threshold amount of C-peptide at baseline. C-peptide is the accepted marker for beta cell mass and function. That is what we're trying to preserve, the organ being attacked in type 1 diabetes. We need to have a meaningful amount to preserve. Those are the two key inclusion criteria: newly diagnosed and a certain amount of C-peptide at baseline.
Got it.
Which is 200 picomolars per.
L.
Liter.
Yeah.
Baseline.
Yeah. And then, just the choice of endpoint, like, essentially, like, it's a one-year follow-up, right, for the study that you're trying to show. Yeah, what would constitute, like, good data, on the endpoint that you're pursuing?
The primary endpoint is, C-peptide at one year, which, again, is the, the measure of the body's ability to make their own insulin, the measure of beta cell mass. Preservation of C-peptide as compared to placebo at one year. The study is powered for 40% preservation. Thymoglobulin has always showed 50% preservation.
Mm-hmm.
Fifty percent preservation of C-peptide compared to placebo. There are also secondary endpoints that relate to glycemic control, which includes time in range, which is a measure of the amount of time the patient is in the normal glucose range. We can capture that because patients wear continuous glucose monitors now. You may be aware type 1 diabetes patients have a sensor on their arm that they wear all the time that's constantly measuring their glucose levels. Time in range and HbA1c, which is a pretty good marker for showing glucose control over the last three months.
Yeah. Got it. Okay. And then just in terms of, like, the timing for this readout then, yeah, where are you on the overall study status? And when can we start to see the data?
We're starting the trial now. It is starting. It's underway. We plan on having data second half of 2027. That's data from a pivotal trial that will show definitively that the drug is efficacious and also that it will be a best-in-class product.
Yeah. And then, when you think about, like, the overall registrational path, is it, like, one phase three after this, or can?
We believe this will be sufficient for an approval.
For the, it can qualify as a registrational study?
We do have agreement with FDA that this qualifies as a registrational study.
Oh, interesting. Is this a SPA, like,
We don't have a SPA, but we have, had a type B meeting.
Okay.
It's a formal meeting. We have, you know, approved, we have agreed-upon minutes from that meeting.
Got it.
The study was designed and powered to be pivotal. The FDA agrees that it is so.
Yeah. Okay. And then, yeah, when do you expect, like, just going back to the study dynamics, like, when do you expect the T-cell exhaustion to start to wear off? Is it, like, a more one-year, six-month time horizon, or,
Yes. That's a good question. It certainly sustained through 180 days, and then there is some waning. Now, Thymoglobulin has the same mechanism and the same sort of durability. They give one dose and measure at 12 months. They can only give one dose because it is not safe to give a second dose. There is no second dose of Thymoglobulin. While we know the effect wanes after 180 days, and there is still a clinical benefit and very good results at 12 months, we actually, because of, and the key differentiator of our drug is we will redose. In the Safeguard trial and in the eventual product profile, it will be redosed every six months. We can, you know, bring that effect back on and hopefully have even better preservation of C-peptide.
that's not necessarily part of the study design that you're redosing, or?
Red in the study, they get.
Okay.
The patients will get another dose at six months.
Okay. But, like, is there subsequent dosing after that, or is it, like, after?
It's a one-year study. The study's over at 12 months.
Oh, okay.
Yeah.
Got it.
There is a long-term extension.
Yeah.
Patients can continue to get dosed.
Oh, okay. But every, all the participants are getting the second dose, or is it only if your effect wears off is when you get the?
Everyone gets a dose at six months.
Okay. Perfect. And then, yeah, in terms of just, like, the, you know, if there is any published literature around what effect size is considered good to be, based on, like, scientific consensus or, in, in the, in for C-peptide, what, what?
Yeah. I mean, what, what's published or the PROTECT, the PROTECT data.
Right.
has a certain preservation. And then Thymoglobulin has a certain preservation. And.
Right.
Any preservation of C-peptide is the drug working because this is an autoimmune disease where autoantibodies are attacking this organ. The first-line therapy's goal is to preserve the organ. That is the goal in any autoimmune condition. You have to preserve that organ. There is nothing better for a patient than to make their own insulin. Any amount of insulin is better than exogenous insulin.
Yeah, but as you do, like, more work with the KOLs in the field.
Mm-hmm.
Is there, yeah, more or less of an adoption based on, like, the C-peptide effect that?
Yeah. There's been no drug approved to date.
Right.
and what we see is 50% preservation with Thymoglobulin.
Right.
That's the standard right now, and less with TZIELD, which is gonna get approved and is going to go to market first.
Yeah.
What I would say in terms of adoption is that if our drug, which we expect, has more preservation than TZIELD, that it'll be more attractive to the physician to prescribe.
Definitely. And then, just, I know this might be a little bit premature, but just thinking about, like, pricing in this type of market, is it effective, like, offering pricing? Would the TZIELD as a good comp to look at it? What's the right way to figure?
TZIELD is priced at $200,000.
Right.
That's kind of the basis we have to think about.
Mm-hmm.
Is that sort of high price point indication?
Right.
$200,000.
Okay. All right. And then, yeah, just in terms of, like, your other follow-on opportunities, like, beyond this, are there any other indications, platform that you're pursuing beyond?
Our drug, SAB-142, is an immunomodulator that leads to self-tolerance.
Okay.
There are multiple T-cell-mediated autoimmune diseases, which include, like, scleroderma. We believe that if the drug is efficacious in type 1 diabetes, it will be efficacious in other autoimmune conditions and certainly has the ability to be a franchise-like product. In addition to that, Thymoglobulin, our reference drug, is the standard of care in organ transplant. To have a human version of a rabbit drug is immediately perceived as superior. We have a lot of inbound interest from transplant surgeons.
Mm-hmm.
We expect to be able, you know, just to replace Thymoglobulin in general.
Got it. Okay, but, yeah, kind of the focus for you right now is just get this study running, and, sort of enroll it. That's the primary focus for the pipeline right now?
Yes.
Is this like, global trial, U.S. trial, or?
This is a global trial.
Okay.
We're opening sites in the U.S., Europe, U.K., Australia, and New Zealand.
Yeah. Like, when you think about the overall opportunities, is U.S. a much bigger contributor in that, or is XUS can also be, like, a sizable commercial opportunity?
I mean, the commercial opportunity in, you know, Western Europe, Australia is, you know, probably doubles the market. So there's a big opportunity, worldwide.
I know, like, I mean, if you have the example of Prevention Bio, like, in this case, ultimately, do you think that, is it go-alone strategy from a commercial standpoint that might be the right approach, or is there any potential, like, strategic collaboration or external, you know, help that you could get on that front?
I think a lot of.
Right.
There are multiple partners that want to be, providing treatments for patients with type 1 diabetes.
Right.
Sanofi wants to be dominant. They're making a big investment there. They are an investor in SAB, and we think that it's a pretty likely outcome that this will be a partnered product.
Got it. Okay. Just, yeah, maybe if you can talk a little bit about just where the balance sheet is with SAB and just kind of talk about the financials.
Sure.
As of August 31 of this year, we have $164 million in cash that should fully fund this phase 2B Safeguard registrational study, and beyond that. We will have cash through 2028 with that cash on hand. Right. What's the rough, like, cash burn that you've been at, like, on an annual basis? In the past, it's been about, you know, $30-$40 million a year. As our phase two ramps up, you can see a meaningful increase next year.
Right.
just as we begin to, you know, initiate sites and roll patients, etc., etc., but we should have cash through 2028. Got it. Okay. Is this the study that you're doing through a CRO or self, self-operation?
Okay.
Yeah.
Got it.
It's a big global study, more than 60 sites.
Yeah. It's hard to do that on, you know, like, with the footprint that you have. Okay. I mean, is there any other competitive, like, outside of the TZIELD that you mentioned? Any other competitive pipeline program that you're looking out for in this space?
When we think about treatment for type 1 diabetes, there are three approaches. The one that is very exciting and a lot of people talk about is cell therapy, which is actually replacing the beta cells. Vertex has a program called VX-880. There is Sana and Sernova. That is an exciting place and hopefully will provide, you know, great outcomes for patients. That is a different market. Those are mature type 1 diabetes patients that have already lost their beta cells.
Right.
Not only does that not compete with our program, but those programs still need to preserve beta cells. There is still a need for immunomodulation. On the other side of it, there are drugs that can improve beta cell health or make beta cells maybe function better, like the GLP-1. That is a great opportunity in type 1 diabetes. It is important to note that those do not preserve beta cells. Those therapies will require immunomodulation to work. There is immunomodulation, which is preserving the beta cells, which is the most important thing. It is fundamental. That is what we do. We believe we will be the best-in-class product. In terms of what is happening on the horizon, I think that our program is the most exciting program happening right now.
Great. Great. Like, as the TZIELD commercial launch has, you know, been successful, has that sort of, like, driven more focus on you guys to look at the next, you know, next innovative thing in this space?
Yeah. I think TZIELD and Prevention, TZIELD and the Sanofi acquisition sort of blazed the path.
Yeah.
It opened the market's eyes to this unmet medical need that people were not really paying attention to. It has been very helpful for us to have TZIELD in front of us.
Right. Okay. Great. Yeah, I mean, that's all the questions that I had. So yeah, if you have any closing thoughts, we can do that, and we can wrap it up after that.
Sure. We are very excited to have the Safeguard trial underway. It is a pivotal study. We have high confidence in the drug's ability to be efficacious or likelihood of being efficacious from the recent MELD results in Thymoglobulin.
Right.
We're very excited about the certainty in the regulatory path that has been established by TZIELD. They recently got a CNPR for TZIELD, Sanofi. They filed an sBLA, and a decision is coming soon. We have clarity and certainty around the regulatory path with TZIELD and Sanofi. We have high confidence in efficacy with the recent Lancet paper with the MELD data from Thymoglobulin. Now we're starting the phase 2b, which is pivotal and should provide definitive efficacy. We're looking forward to executing on that trial and delivering results.
Great. Thank you so much for joining the conference and, looking forward to, you know, updates from the clinical trial.
Thank you. Thank you for having us.
Yeah. Thanks for having us.