Great. Thank you, and welcome everyone to our next presenting company here at Oppenheimer's 36th Annual Healthcare Life Sciences Conference. I'm Leland Gershell, one of the Biotech Analysts with the firm. We are gratified and delighted to have with us SAB Biotherapeutics. The ticker is SABS, which we cover within our perform, and we like the story very much. We have with us from the company, Sam Reich, who's the Chief Executive Officer. We'll be having a fireside chat with Sam, and if you have any questions you'd like to pop in, please submit those through the portal. Welcome, Sam.
Thank you. Good morning. Nice to be here.
Great. I think, you know, there may be some who are less familiar with the SAB story. You know, if you could just kind of, you know, give a quick intro to your mission, the asset that you're developing, what indications you're pursuing here in type 1 diabetes.
Our mission at SAB BIO is to transform what it means to get a type 1 diabetes diagnosis by developing a therapy to change the course of disease and not just manage the symptoms. We're a clinical stage biotech company with our lead asset being an anti-thymocyte globulin for the treatment of type 1 diabetes. Our lead product is called SAB-142. It's a human anti-thymocyte globulin to immune modulate and lead to self-tolerance in patients with type 1 diabetes to preserve their beta cells or the cells that make insulin. We are currently studying it in a Phase IIb trial, which has a pivotal study. Type 1 diabetes is a multi-billion dollar market opportunity.
It's a major unmet medical need, and there's a tremendous urgency by the patient and doctor community for new therapies to help these patients continue to make their own insulin. Our drug is made on a wholly owned platform, which is called Tc Bovine, which allows us to make fully human immunoglobulin drugs, and that gives us multi-level intellectual property protection, which includes trade secrets, know-how, patents, your typical biotech patent lifespan, as well as the fact that this drug modality has no biosimilar pathway. There's no pathway within regulatory agencies to make a generic version of this drug, which gives SAB-142 really long-term exclusivity.
Great. That's a great intro. You mentioned, yeah, so Tzield, this is a Sanofi product. This was, you know, first approved about three, four years ago to delay the onset of Stage 3, type 1 diabetes, in those eight years and older with Stage 2 disease. That's given as a 14 day IV course and, you know, delays progression by about two years versus placebo. You know, how has that approval changed the landscape in terms of, you know, all running the gamut, screening, diagnosis, and then also expectations for disease-modifying therapy here? How does that unmet need differ, you know, by age and stage in the scope of the diabetes illness?
Okay, that's a multi-pronged question. Let's start with how did it change the field? I mean, the prevention drug Tzield, and then the acquisition by Sanofi. Now Tzield is a Sanofi drug, is a monoclonal against T cells, and it was approved in Stage 2, which is an earlier stage indication, which we can talk more about. It really showed doctors, patients, Wall Street, the fact that this is a big unmet medical need, that there's more to do than just manage patients with insulin. That preserving beta cells has a clear benefit to the patients. In Stage 2, when Tzield preserves beta cells, it gives the patient more time before they need insulin, which is delayed progression of the disease.
That really shed light on the space and paved the way for the space. Stage 2, the indication, in which Tzield is approved today, is a much smaller market. These patients are hard to identify because they're not symptomatic, and they have to go in and voluntarily screen for autoantibodies. It's a much smaller and very different market than Stage 3, our initial market, and hopefully, Tzield will be approved in Stage 3, where the vast majority of the patients are diagnosed and identified. Demonstration that we can intervene with these patients and preserve their ability to make insulin was really groundbreaking, and we're very, you know, very grateful to the Tzield developers for that.
Now, could you know, let's focus on your asset, SAB-142. Can you walk us through, you know, really how that works? You know, we know it as a kind of fully human, not humanized, but fully human, bovine-derived, polyclonal antibody product that's designed to basically, you know, exhaust pathogenic CD4 T cells while preserving Tregs.
That's right.
Could you kind of maybe, you know, expound a bit on that and why that's kind of the way to go here with respect to preserving beta cells?
Yes. Just as a general background, type 1 diabetes patients or autoimmune patients that have autoantibodies attacking the beta cells of their pancreas where insulin is made. A first-line therapy should preserve beta cells so patients can continue to make their own insulin. Our drug, SAB-142, is a human anti-thymocyte globulin which induces T-cell exhaustion while preserving Tregs, which has been shown to preserve beta cells and improve glycemic function. It's been shown with a reference analog, that mechanism of action has been proven by a drug called Thymoglobulin, which is a rabbit anti-thymocyte globulin, which induces T-cell exhaustion while preserving Tregs.
The results with Thymoglobulin in newly diagnosed type 1 diabetes patients is that after receiving the drug, they have preserved beta cells, as compared to placebo, and they have reduced HbA1c as compared to placebo. This mechanism of action, that SAB-142 has been validated by a rabbit version of our drug. The rabbit version of our drug has safety problems and can't be redosed. This is a chronic disease. The two liabilities for Thymoglobulin or the rabbit drug, which is proven to be efficacious, is that it causes serum sickness, and it can't be redosed because of the generation of anti-drug antibodies, as well as serum sickness. That is because it is a rabbit polyclonal antibody. Our drug is a human polyclonal antibody.
We have already shown it does not cause serum sickness, and it can be redosed, and these patients need chronic dosing. We have the mechanism of action that's proven efficacious to preserve beta cells and improve glycemic control, and by making a human version of the rabbit drug, we have a drug that does not cause serum sickness and can be redosed. This has a acceptable safety profile for long-term chronic use to continue to preserve the patient's beta cells as long as possible, for their whole lives, perhaps.
You know, how should we, you know, think about 142 then, you know, and the way it works as translating into a much better safety profile, you know, versus rabbit ATG? I mean, clearly issues here with serum sickness and also, you know, lymphodepletion.
Yes. There are 3 key differences between rabbit anti-thymocyte globulin and human anti-thymocyte globulin. The first is, because it's foreign, it causes serum sickness, which, comes, like, one week after dosing. The patients have moved on, and then they get these horrible, symptoms of rash and fever and are really miserable for several days, and it's one week later, so it's very tough to manage. Also, serum sickness would be worse upon redosing, and it can be fatal, so redosing would be very dangerous. The rabbit molecule, rabbit foreign protein, is also immunogenic, and the patients, the majority of patients, develop anti-drug antibodies. In addition to the serum sickness, the drug can't be redosed for efficacy reasons, because the drug will, every time it's dosed.
It's only been dosed once to date but would become ineffective due to neutralizing anti-drug antibodies and would be very unsafe due to serum sickness. Lastly, the rabbit antibody, the Fc receptor on the rabbit antibody, induces antibody-dependent cell killing, or ADCC, and that actually kills important immune cells, and T cells and lymphocytes. That suggests that those patients may be immune-compromised, which is something we really don't wanna do for chronic use or young patients or patients that would otherwise be healthy. The human Fc receptor and the human anti-thymocyte globulin does not cause serum sickness, shows no ADAs. We've already shown we can redose, and the second dose has the same effect as the first dose and does not lymphodeplete because the human Fc receptor on our drug does not lead to antibody-dependent cell killing.
The patients should be fully immune competent and then be something suitable for chronic use without fears of immunocompromising the patients.
Right. That could be a really big feature, right? Retreatment, you know, maybe a couple times a year even with yours versus the rabbit, which I don't think you can really give more than once or twice 'cause of the immune risks. You have the SAFEGUARD Phase 2b study, which you've moved into, and this is in newly diagnosed Stage 3. Just to be clear for everyone, you know, Stage 3 and Stage 2, sometimes people get confused, right? Stage 3 is when people actually have, like, diagnosable clinical type 1 diabetes, and Stage 2 is kind of the, you know, you're sort of biologically going in that direction but not manifesting clinically, like you do in Stage 3.
Can you know, for us, outline, SAFEGUARD's key features in terms of, you know, the patients you're enrolling, as well as the dosing regimen? You're looking at a primary endpoint of C-peptide. Maybe tell us a bit about that and the regulatory, you know, implications. Also, of course, the other endpoints like insulin and HbA1c, which everyone knows in the diabetes space. You know, what would you see here as being clinically meaningful here that would be impactful to practice?
The SAFEGUARD study is a global Phase IIb study in newly diagnosed type 1 diabetes patients. That is Stage 3, newly diagnosed Stage 3, type 1 diabetes patients that are within 100 days of diagnosis. There are three arms. The patients are from age five to 40, so we have adults, pediatrics, and adolescents, the whole sort of age range. There are three arms: 2.5 mg per kg, 1.5 mg per kg, and placebo. The patients will be dosed every six months with one of those three arms. The arms will be stratified by age. There will be a relatively even distribution of adults, adolescents, and pediatrics. The primary endpoint is C-peptide at year one. You asked a little bit about C-peptide.
C-peptide is the validated, accepted endpoint that shows beta cell mass and function, some combination of beta cell mass and function. The objective for treating a newly diagnosed patient is to preserve beta cell mass and function. That is the patient's ability to make their own insulin. The endpoint is preservation of C-peptide, and if you do that, your drug is efficacious. A clinically meaningful preservation of C-peptide is generally considered to be 40% preservation compared to placebo. These patients have other things going on, so we certainly want to look at other secondary endpoints, and right now it's not quite clear how essential they are for regulatory approval. The secondary endpoints people are interested in, which we'll all be looking at, are HbA1c.
If you reduce HbA1c, you've proven that the patients have better glycemic control, which translates to many, many benefits in health. Insulin use, frequency of hypoglycemic events, which can be quite, you know, just are very apparent to patients in their day-to-day management of the disease, and Time in Range, which is now that patients wear continuous glucose monitors, we can measure how much time they spend in range, which actually is probably slightly more precise than HbA1c, which gives you a ballpark about range and Time in Range, shows us in real time how much time the patients have, are in the normal range.
Terrific. In terms of full enrollment and top-line data, I think you've given some guidance there, if you could reiterate that?
We're planning, and on track to have the last patient in by the end of 2026, this year, and be able to share top-line data from the trial in the second half of 2027.
All right, terrific. You know, the rabbit ATG, so that, the MELD trial, which I think you would have referenced or so I've seen data from that relatively recently. You saw improvements in C-peptide and in A1c in newly diagnosed patients. We did see, as you had also mentioned, you know, sustained, meaningful lymphodepletion, you know, in CD4 and CD8 T cells, at least at the 2.5 mg per kg dose cohort and some other safety concerns. I mean, what have we learned from the MELD ATG dataset and maybe some other ATG experiences that you've baked into your development of, SAB-142 in its design and dosing? Are there other competitor or interim readouts, in type 1 diabetes immunotherapy that we should all just sort of have in our radar, as you continue to execute on SAFEGUARD?
Yeah. As a, before MELD, there was a trial called TN19. TN19 was conducted by TrialNet, which is a U.S. consortium of diabetes researchers, and that was a study in newly diagnosed patients that were given a low dose of Thymoglobulin or placebo, and at one year, they showed meaningful preservation of C-peptide and a reduction in HbA1c, both statistically significant. That's the foundation for our program. The drug did everything that we want it to do after a single dose, and really and sort of set the basis for our program because it still was encumbered by serum sickness and the inability to redose. MELD was conducted.
Another very similar study, it was conducted by European researchers in INNODIA, and it was a very similar study, but they dose ranged to lower doses. That data came out in September, and for a second time, in a second patient set with the same drug, Thymoglobulin showed it preserved C-peptide and reduced HbA1c. Really, very firmly establishing this mechanism of action and drug modality as efficacious in this, in these patients. What we learned new in MELD that we hadn't learned in the TN19 study was related to dose ranging. What we saw was.
If the anchor dose or the established effective dose was 2.5 mg/kg, and in MELD, they included lower doses and carried forward 0.5 mg/kg and compared it to 2.5 mg/kg at one year. 0.5 mg/kg also showed efficacy. It showed preservation of C-peptide and reduction in HbA1c. For a second time, we see that Thymoglobulin is efficacious, or this mechanism of action is efficacious, and we also learned that lower is still efficacious, and so there is a kind of a Goldilocks dose with this drug therapy, which we learned from MELD, which is very helpful.
Also, the lower dose had less lymphodepletion, so lymphodepletion has now been sort of officially separated from efficacy, and as our doesn't have lymphodepletion, that provides even more confidence that lymphodepletion is a liability and not a benefit. If you go low enough, you can lose exhaustion, 'cause they had a lower dose they dropped, and we can look at lower doses and see you don't have exhaustion. You can't go too low, but you don't want to go too high, which was, you know, firmly established by MELD. We really have a large amount of data and support for our program guiding us and reducing risk.
All right, good. SAFEGUARD has been described by you guys as a registrational intent trial. You know, how should investors think about that in practical terms? I mean, would this, you know, say, for single phase IIb be sufficient for approval? We did see the FDA come out with its statement recently that, you know, a single pivotal study could be sufficient for most cases for approvals. You know, would there be additional safety or durability, potentially real-world data that may be of interest to regulators, you know, as they contemplate, you know, your guys' program becoming, commercially available?
We have agreement with FDA that this is a pivotal study. We have, you know, the right powering, the right endpoints, the right patient population for this to be a registrational study, so it's kind of a de facto phase III. We believe, based on precedent and our experience, in this space, that it will be sufficient. We do have time between now and BLA, to augment the program, without causing any delays. Were there to be more patients needed or more exposure needed, we'll have time and dialogue with the FDA to add any programs needed between now and then. At this point, we do believe it's sufficient, and we are planning on any kind of additional studies now that, you know, we believe would be supportive of filing and getting an approval on the same.
Great. Yeah. Okay, good. As we look toward, you know, it's a little bit of time away, you know, second half 2027, are there other events coming out of the company, presentations, maybe regulatory interactions? Although it sounds like you guys are pretty much caught up there. I don't know, biomarkers. Anything else that we may see that could kind of help investors learn more,
Yeah.
About the progress?
A few things we can look forward to in 2026 are, of course, enrollment updates, which allow everyone to sort of track the time to that major event of turning over data. We do have sort of more interesting data from our phase I that we completed and locked out last year, that we'll be sharing at scientific venues, which we think, you know, are interesting updates for the market. Any program updates as it relates to, you know, building on our type 1 diabetes program with SAB-142 and building our data set, we'll announce this year.
Excellent. Great. You know, the commercial opportunity here would seem to be pretty sizable, given the transformative potential of 142. Could you know, walk us through as what you see, as the addressable market, in newly diagnosed, Stage 3, and, you know, how could that expand if you move earlier into Stage 2, sort of a prevention, type of setting, you know, also considering retreatment? How are you beginning to think about pricing, you know, in a post, Tzield world?
Yeah. There are 64,000 new patients diagnosed every year in the U.S. alone. That is an addressable market. We need to preserve their beta cells. In addition to that, we have redosing, so we will accumulate patients, which increases that overall market size. We do want to go earlier and catch patients earlier in Stage 2, and I think right now it's hard to quantify that increase in the TAM, 'cause the vast majority of the addressable market today is newly diagnosed patients. As the field progresses, we believe there are interventions available, we believe more and more patients will be diagnosed in Stage 2, and we want our therapy to be available to them, and that offers the promise of keeping a patient insulin-free.
We plan on studying the drug in Phase II, eventually getting that added to the label, and there's probably some nominal increase to the available market. As patients get diagnosed in Stage 2, we want to be there for them to preserve their beta cells and perhaps keep them insulin-free. As far as pricing, it's very early days. We're just beginning to build out our commercial program and prepare for that. What I can say is that right now, Tzield is priced at $200,000. That's a guidepost. You know, it's very early days, but, you know, technically speaking, when you have a superior drug, you can charge a premium for it, and that's where we are in pricing today.
Okay. What, what, you know, what preparatory work are you doing already on the commercial front? You know, market development, key opinion leader engagement, maybe kind of a screening infrastructure. You know, how are you weighing also kind of go-it-alone launch versus partnering with, a larger company, you know, that may be in the diabetes or immunology space?
Well, you know, as a business and a board of directors and management team, we are prepared and ready to launch this drug and be a commercial company. We are beginning to explore the patient-provider journey, willingness to pay, where the market is, where the patients get diagnosed, and what we need to address with what kind of a force, which I think should be relatively small because most of these patients are treated at institutions, something very addressable. Early, early messaging around how this drug can help patients and why they should use it. A lot of planning so that we're ahead of the curve.
You know, Tzield recently qualified for the new commissioner's priority review voucher. Sanofi recently filed an SBLA based on the PROTECT data for Stage 3. You know, seems like a supportive development for the, you know, overall effort here in terms of SAB. How, you know, how does that inform or validate the broader opportunity for disease-modifying therapies like SAB-142, and, you know, any precedent here that impacts your own regulatory strategy?
Sanofi filed an SBLA. For Stage 3 type 1 diabetes, they have only hit on C-peptide. They didn't hit on secondary endpoints. If we believe that they had interacted with FDA and got agreement, that suggests that they have agreement that C-peptide is sufficient for an approval, which, you know, just lowers the bar or the threshold for getting a drug approved. We believe we'll hit on secondary endpoints based on what we know of our drug and Thymoglobulin. Worse, Tzield to get approved in Stage 3, it would create a precedent and establish that the FDA believes C-peptide is sufficient for an approval. We'll see. Hopefully, we'll hear news soon.
Yeah. No, good one to watch. As we think about, you know, SAB-142 and Tzield, you know, you know, if you have those on the market ultimately targeting overlapping patient populations at different stages, you know, how do you envision, you know, their roles, you know, kind of in a, in a sequential format, competitively, complementarily? Do you see a potential scenario in which a newly diagnosed, you know, type 1 diabetes patient initially receives Tzield, given that Tzield is not really intended for repeat use, could then that patient subsequently receive SAB-142 as a maintenance therapy?
That's a great question. There's two very key differentiations which give SAB-142 advantages over Tzield. First, to date, in all the clinical trials, Tzield has not shown a reduction in HbA1c. It has shown a preservation of C-peptide, but not reduction in HbA1c, whereas the mechanism of action we employed has shown both. With that, one conclude it has superior efficacy. That's a pretty big differentiator if we get that. If you just take the dosing regimen alone, Tzield requires 12 days of dosing, and Thymoglobulin and SAB-142 require two days of dosing. We have talked about this extensively with the doctors that treat these patients.
The 12 day dosing is very difficult, and it's leading to a lot of patients who just say no, and actually, some patients who are hearing about, like, our clinical trial are just waiting. If the drugs had similar efficacy, and we believe ours is superior, 12-day dosing versus two-day dosing, and we have real-world knowledge, is a massive differentiator. We do believe that will be very competitive. In terms of follow-up dosing, I would hope a Tzield patient could get our drug. I mean, that's not something we're studying. I know that it's something of great interest 'cause there would be patients that got Tzield that will want to continue to preserve beta cells. That's some possibility out there, but, you know, it's not something we're exploring. We do believe that we will take significant market share due to superior efficacy and a vastly superior dosing regimen.
Almost at the time here, but just want to review kind of catalysts for the company. Completion of enrollment and SAFEGUARD by end of this year, looking at top-line data, second half of next year. You've been successful in your financing pursuits. Cash balance, if you could remind us your runway?
At the end of 25, we had $140 million in cash. The runway fully funds SAFEGUARD through top-line data, plus about a one year runway, so we have cash through 2028.
Excellent. Great! Well, I think we'll conclude here. Thank you all for Zooming in. Thank you, Sam, for joining us. Looking forward to everyone coming to one of our next sessions here at the conference. Have a great day.
You too. Thank you for having me.
Thanks.