SAB-142 / SAb Biotherap - LARVOL DELTA

SAB-142, a fully human anti-thymocyte globulin, demonstrated anticipate pd profiles and early efficacy signals in type 1 diabetes patients with residual C-peptide (EASD 2026) - P1 | "Administration of SAB-142 in T1D patients was both safe and led to C-peptide preservation (4/4) and possible islet beta cell recovery (3/4) in subjects with T1D >100 days. Early signals of patient benefit were also detected in this cohort with glucose TIR increasing >16% in the SAB-142 treated group compared to baseline."

Clinical • First-in-human • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus • CD4 • PD-1 • TIGIT

SAB-142, a fully human anti-thymocyte globulin, can be safely readministered, is not immunogenic, and has predictable PK/PD profiles in healthy volunteers (EASD 2026) - P1 | "Repeat administration of SAB-142 in healthy volunteers was safe, did not induce measurable immunogenicity, and showed consistent PK profiles. PD biomarkers were also consistent following induction and maintenance doses. Taken together, these data indicated that repeat administration of SAB-142 is well tolerated and may allow for the extension of beneficial immunomodulation in T1D patients."

Clinical • First-in-human • PK/PD data • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Mechanism of action of SAB-142 and responsive C-peptide signal in adult patients with type 1 diabetes > 100 days post diagnosis (EASD 2026) - P1 | "SAB-142 promoted the sustained increase of inhibitory receptor expression on CD4s in HVs in the absence of cytotoxicity. This effect, along with the observed preservation and activation of Tregs, suggest a MoA that may suppress the T-cell specific killing of beta islet cells potentially restoring beta cell heath as measured by improved C-peptide production. This MoA is further supported in the T1D patient cohort which demonstrated signals of efficacy with improved C-peptide preservation and glycemic control in response to SAB-142 treatment."

Clinical • First-in-human • IO biomarker • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus • CD4 • TIGIT

A Phase I Randomised, Double-Blinded, Placebo-Controlled, Single Ascending Dose Adaptive Design Study Assessing the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intravenous SAB-142 (ANZCTR) - P1 | N=90 | Completed | Sponsor: Sab BioTherapeutuics | Recruiting ➔ Completed

Trial completion • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

PRISE-hATG: PRISE (Personalized Response and Immunologic Surveillance of Endogenous C-Peptide Preservation in New, Recent, and Established Onset Type 1 Diabetes Treated With Human Anti-Thymocyte Globulin [h-ATG]) Study (clinicaltrials.gov) - P3 | N=108 | Not yet recruiting | Sponsor: University of Florida

New P3 trial • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Clinical Safety, Pharmacokinetics, Immunogenicity, and Pharmacodynamics following Repeat Dosing of SAB-142, a Fully Human Multispecific Antithymocyte Globulin for New-Onset Type 1 Diabetes (ADA 2026) - "Clinical data from SAB-142-101 demonstrated a favorable safety and immunogenicity profile, consistent PK, transient cytokine increase, and a PD profile indicative of the desired mechanism of action suggesting safe re-dosing every 6 months as a maintenance dose and supporting advancement to the Phase 2B SAFEGUARD study in pediatric and adult NOT1D patients."

Clinical • IO biomarker • PK/PD data • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus • CD4 • CD8 • TIGIT

Positive Clinical Translation of a Juvenile NHP Study for Evaluating SAB-142, a Multi-Specific T-Cell Targeting T1D Therapy, in Humans (FOCIS 2026) - "This effect was observed in both cynomolgus monkeys and in human subjects evaluated in the Phase 1 study.ConclusionsThe positive translational value of this 9-month, two-dose chronic GLP toxicology study was supported by Phase 1clinical data, with both studies suggesting lymphocyte margination not sustained lymphodepletion across all tested dose levels of SAB-142. In the Phase 1 clinical study, peripheral lymphocyte counts returned to baseline by Day 7, in both healthy volunteers and patients with stable T1D, confirming the clinical translation of the transient pharmacodynamic effect observed in this preclinical toxicology study in cynomolgus monkeys."

Clinical • First-in-human • Immunology

SAFEGUARD: SAFety and Efficacy of Human Anti-thymocyte ImmunoGlobUlin SAB-142 ARresting Progression of Type 1 Diabetes (clinicaltrials.gov) - P2 | N=159 | Recruiting | Sponsor: SAb Biotherapeutics, Inc.

Trial initiation date • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

POSITIVE CLINICAL TRANSLATION OF A JUVENILE NHP STUDY FOR EVALUATING SAB-142, A MULTI-SPECIFIC T-CELL TARGETING T1D THERAPY, IN HUMANS (ATTD 2026) - "The positive translational value of this 9-month, two-dose chronic GLP toxicology study was supportedby Phase 1 clinical data, with both studies demonstratingno sustained lymphocyte depletion across all tested doselevels of SAB-142. In the Phase 1 clinical study, peripherallymphocyte counts returned to baseline by Day 7, in bothhealthy volunteers and patients with stable T1D, confirmingthe clinical translation of the transient pharmacodynamiceffect observed in this preclinical toxicology study in cynomolgusmonkeys."

Clinical • First-in-human

TRACKING MULTIPLICITY: IN VITRO AND CLINICAL PHARMACOKINETIC ASSAYS FOR MULTI-TARGET THERAPEUTICS (ATTD 2026) - "SAB-142 binds to several receptors on T-lymphocytes in a pattern similar to rabbit ATG (rATG). The data from SAB-142 Phase 1 study demonstrated a dose-proportional PK profile for SAB-142, with no major differences in systemic exposure between healthy volunteers and patients with T1D."

IO biomarker • PK/PD data • Preclinical • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus • CD2 • CD4 • CD8

BETA CELL GUARDIANS: MECHANISM OF ACTION OF SAB-142, AN EMERGING IMMUNOTHERAPY FOR NEW ONSET T1D (ATTD 2026) - "Background and Aims: Clinical studies of rabbit Anti-Thymocyte Globulin (rATG) have demonstrated C-peptide preservation in T1D patients, but its heterologous nature precludes safe and effective redosing. SAB-142 promoted the activation and differentiation of T-cells and their increased inhibitory receptor expression in the absence of cytotoxicity. This effect, along with the observed activation of Tregs, may suppress antigen specific killing of beta islet cells. A lack of serum sickness or anti-drug antibodies suggested the potential to safely and sustainably restore immunotolerance and improve the treatment and prognosis of T1D."

First-in-human • IO biomarker • Diabetes • Diabetic Nephropathy • Metabolic Disorders • CD4 • CD8 • PD-1 • TIGIT

CHARTING THE SAFETY LANDSCAPE OF MULTI-SPECIFIC MODALITIES: SAFETY PROFILE OF MULTI-SPECIFIC ANTI-THYMOCYTE GLOBULIN SAB-142 (ATTD 2026) - "Rabbit anti-thymocyte globulin (rATG) has been studied but is limited by neutralizing antibodies and hypersensitivity. SAB-142 was well tolerated in humans and NHPs. No deaths, serious events, serum sickness, or ADAs were observed. The NOAEL was 50 mg/kg, supporting safe initial dosing and re-dosing at six months with a ~20X safety margin."

Clinical • First-in-human • Diabetes • Hematological Disorders • Immunology • Metabolic Disorders • Type 1 Diabetes Mellitus

DECODING THE BINDING LANDSCAPE FOR MULTI-SPECIFIC T1D BIOLOGICS: TARGETED BINDING OF RABBIT VS HUMAN ANTI-THYMOCYTE GLOBULIN, SAB-142 (ATTD 2026) - "Here, we present the first data on the characterization of human ATG binding to T cell associated CD proteins. Human surface proteins expressed on mouse T cells serve as a conformational system to study antibody targeting. Our in vitro studies indicate a strong similarity in the specificity binding profile of human ATG and rATG, which is consistent with both products being generated using human thymocytes as the antigen for immunization."

Preclinical • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus • CD2 • CD8 • PTPRC

BREAKING THE DEPLETION PARADIGM: IMMUNOMODULATION WITHOUT SUSTAINED LYMPHODEPLETION WITH SAB-142, A FULLY HUMAN, MULTI-SPECIFIC ANTI-THYMOCYTE GLOBULIN FOR T1D (ATTD 2026) - "In contrast, clinical trials with 2.5 mg/kg rabbit ATG (rATG) demonstrate lymphopenia lasting more than 2 years. The emerging safety profile of SAB-142, marked by the absence of sustained lymphopenia, serum sickness, and immunogenicity, supports its use across adult, adolescent, and pediatric populations. Its stronger FcRn binding suggests enhanced in vivo endothelial recycling and lymph node transport. In contrast, rATG's higher FcγRIIIA activation indicates lower concentrations suffice for ADCC, consistent with the long-term lymphodepletion observed in low-dose rATG T1D studies."

Immunomodulating • Immune Modulation • Immunology

SAB-142-201: SAFEGUARD (SAFety and Efficacy of Human Anti-thymocyte ImmunoGlobUlin SAB-142 ARresting Progression of Type 1 Diabetes) Study (clinicaltrialsregister.eu) - P1/2 | N=66 | Not yet recruiting | Sponsor: Sab Biotherapeutics Inc.

New P1/2 trial • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

SAFEGUARD: SAFety and Efficacy of Human Anti-thymocyte ImmunoGlobUlin SAB-142 ARresting Progression of Type 1 Diabetes (clinicaltrials.gov) - P2 | N=159 | Recruiting | Sponsor: SAb Biotherapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

SAFEGUARD: SAFety and Efficacy of Human Anti-thymocyte ImmunoGlobUlin SAB-142 ARresting Progression of Type 1 Diabetes (clinicaltrials.gov) - P2 | N=159 | Not yet recruiting | Sponsor: SAb Biotherapeutics, Inc.

New P2 trial • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Novel pharmacokinetic assay for measuring SAB-142, a fully human anti-thymocyte globulin (EASD 2025) - P1 | "The novel SAB-142 PK assay was developed and validated with a Lower Limit of Quantification (LLOQ) in human serum of 0.25 µg/mL. This assay has been utilized for monitoring PK in a first-in-man, randomized, double-blind, placebo-controlled Phase I study (SAB-142-101). Results from this study demonstrated that the overall drug exposure of free SAB-142, as assessed by Cmax and AUClast, increased in dose proportional manner as the dose was increased from 1.5 to 2.5 mg/kg."

PK/PD data • Metabolic Disorders

Mechanism of action of a fully human anti-thymocyte globulin, SAB-142, for the treatment of type 1 diabetes (EASD 2025) - P1 | "These data suggest SAB-142's MoA involves the activation of CD4 and CD8 T-cells, promoting their differentiation and increased inhibitory receptor expression in the absence of cytotoxicity. Activation of Tregs may contribute to sustained suppression of CD4 and CD8 T-cells involved in antigen specific killing of beta islet cells. Similarities to rATG include Treg preservation and inhibitory receptor induction in CD4 T-cells."

IO biomarker • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus • CD4 • CD8 • PD-1 • TIGIT

Immunomodulation without sustained lymphodepletion: SAB-142, a fully human anti-thymocyte globulin (EASD 2025) - P1 | "For the SAB-142-101 trial, only transient peripheral lymphopenia was observed over the initial days of dosing. The emerging safety profile of SAB-142, with lack of sustained lymphopenia, is a major safety advantage of SAB-142. No sustained depletion of major blood cells, coupled with the lack of serum sickness and immunogenicity, creates a favorable SAB-142 safety profile for the target patient population across adult, adolescent, and pediatric age groups."

Immunomodulating • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus • CD4

SAB BIO Announces Q1 2025 Financial Results and Provides Company Updates (GlobeNewswire) - "R&D expenses were $7.7 million and $8.1 million for the three months ended March 31, 2025 and March 31, 2024, respectively. The modest decline resulted from the fluctuation of priority spending for the SAB-142 program, a disease-modifying human hIgG aimed at preventing onset or disease progression of T1D."

Commercial • Type 1 Diabetes Mellitus

SAB BIO Announces Q1 2025 Financial Results and Provides Company Updates (GlobeNewswire) - "In April 2025, SAB BIO concluded patient dosing in the last cohort of the Phase 1 clinical study of SAB-142....The Company has successfully obtained a Qualified Person (QP) declaration for SAB BIO’s in-house CMC manufacturing process for SAB-142. This milestone represents a key cGMP compliance achievement enabling SAB BIO to meet European manufacturing standards for an investigational medical drug product (IMPD) designated for upcoming clinical trials in the EU."

Commercial • New trial • Trial status • Type 1 Diabetes Mellitus

SAB BIO Announces Positive Topline Phase 1 Clinical Results with Potentially Disease-Modifying T1D Therapy SAB-142 (GlobeNewswire) - P1 | N=78 | ACTRN12623001089628 | Sponsor: Sab BioTherapeutics | "SAB BIO...announced positive topline data from a Phase 1 trial of SAB-142 in a single-ascending dose among healthy volunteers....Favorable Safety Profile: SAB-142 was generally well-tolerated and demonstrated a favorable safety profile that supports the chronic dosing of SAB-142 in an ambulatory setting. The SAB-142 Phase 1 dose range was between 0.03mg/kg up to 2.5mg/kg, which demonstrated favorable safety profile based on the 0% reported serum sickness and anti-drug antibodies. Sustained Immunomodulation: SAB-142 demonstrated a clinically validated multi-target MOA with sustained immunomodulation."

P1 data • Type 1 Diabetes Mellitus

SAB BIO Announces R&D Webinar Event to Review Phase 1 Topline Results for SAB-142, a Disease-Modifying T1D Therapy (GlobeNewswire) - "SAB BIO...announced today that the Company will host a Research and Development webinar on January 28, 2025 to discuss the topline data for Phase 1 clinical trial for its lead candidate, SAB-142."

P1 data • Type 1 Diabetes Mellitus

A Phase I Randomised, Double-Blinded, Placebo-Controlled, Single Ascending Dose Adaptive Design Study Assessing the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intravenous SAB-142 (ANZCTR) - P1 | N=78 | Recruiting | Sponsor: Sab BioTherapeutuics | N=38 ➔ 78

Enrollment change • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus