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Item 1. Business

2025-03-31 compared with 2024-03-29 · 163 added, 281 removed, 240 unchanged (65% of the section changed)

We are a clinical-stage biopharmaceutical company focused on the development of human polyclonal immunotherapeutic antibodies, or human immunoglobulins (hIgG), to address immune system disorders and infectious diseases.

Our antibodies are both target-specific and polyclonal, meaning they are comprised of multiple hIgGs and can bind to multiple sites on specific immunogens, making them ideally suited to address the complexities associated with many immune-mediated disorders.

Our lead candidate, SAB-142 is a human anti-thymocyte globulin (ATG) focused on preventing or delaying the progression of type 1 diabetes (T1D).

We recently initiated a Phase 1 trial of SAB-142 to establish its safety and pharmacokinetic profiles in human subjects.

In addition to SAB-142, we also have clinical stage assets targeting infectious diseases that have significant mortality and morbidity in the general population and in high-risk patients.

To date, we have conducted seven clinical trials, including Phase 1, Phase 2 and Phase 3, totaling more than 700 individuals dosed with our proprietary hIgGs.

In May of 2023, we received Fast Track Designation and Breakthrough Therapy Designation from the Food and Drug Administration Center for Biologics Evaluation and Research (“CBER”) for our SAB-176 immunoglobulin targeting multiple strains of influenza based upon positive clinical data from a Phase 2a trial.

More broadly, we believe that our proprietary platform, referred to as DiversitAb, holds the potential to generate additional novel therapeutic candidates to expand our pipeline.

DiversitAb utilizes the human immune response to generate the optimal repertoire of IgGs for drug targets of interest.

Business Overview

We are a clinical-stage biopharmaceutical company focused on the development of human polyclonal immunotherapeutic antibodies, or human immunoglobulin G (hIgG), to address immunology disorders.

Our programs are based on mechanisms of action that have achieved proof-of-concept in clinical trials in indications with significant unmet medical needs.

We are focused on developing product candidates for disease targets where a differentiated approach has the greatest potential to be either first-in-class against novel targets or best-in-class against complex targets to treat diseases, including type 1 diabetes (T1D) and other autoimmune disorders.

Our internally discovered antibodies are both target-specific and polyclonal, meaning they are comprised of multiple hIgG and can bind to multiple sites on targeted immunogens, making them ideally suited to address the complexities associated with many immune-mediated disorders.

Our proprietary platform holds the potential to generate additional novel therapeutic candidates to expand our pipeline, utilizing the human immune response to generate the optimal repertoire of hIgG for drug targets of interest.

We believe it is the only technology capable of producing disease-targeted, hIgG in large quantities without the need for human plasma donors.

We have optimized genetic engineering in the development of transchromosomic cattle, or Tc Bovine, which produce hIgGs.

Our engineering of the DiversitAb production system drives IgG1 production across our pipeline.

As our lead program SAB-142 advances, we intend to expand our pipeline in complimentary indications through strategic utilization of our platform.

BUSINESS STRATEGY

• We are focused on developing product candidates for disease targets where a differentiated approach has the greatest potential to be either first-in-class against novel targets or best-in-class against complex targets to treat diseases with significant unmet medical needs, including immune and autoimmune disorders including T1D.

• We are leveraging our proprietary production system to advance a robust pipeline of differentiated hIgG-based therapies for the treatment of immune system disorders and infectious diseases.

• Our business strategy is focused on SAB-142 as a first-in-class, human, multi-target antibody treatment designed to provide superior efficacy and safety in delaying the onset or progression of T1D.

• Our production system (DiversitAb TM) represents the first technology of its kind to produce large-scale human high-titer and high-avidity antibodies across multiple modalities.

• We have a demonstrated regulatory pathway through each of the U.S.

Food and Drug Administration (the “FDA”), CBER, UK Medicines and Healthcare products Regulatory Agency (“MHRA”), and Australian Therapeutic Goods Administration (“TGA”).

These organizations understand our science and are familiar with the multivalent and multitarget properties of our single vial drug products.

This further streamlines our ability to develop new and novel drug products rapidly and efficiently where single target monoclonal antibodies (mAbs) cannot replicate or duplicate our drug product attributes.

• Our hIgGs have been safely demonstrated up through Phase 3 clinical trials with a patient safety database that includes over 700 patients who were safely administered our hIgG therapeutics.

RECENT MILESTONES

We have achieved multiple recent milestones, including:

• Initiated a Phase 1 clinical trial of SAB-142 for safety and tolerability in autoimmune disorders including T1D.

• Financing of up to $110 million in gross proceeds dedicated to clinically advance SAB-142 to 2026 and topline Phase 2 results.

• Completed IND enabling in-vivo pilot and GLP toxicity safety and pharmacodynamic studies for SAB-142 for disease-modifying approach for autoimmune disorders including T1D.

• Completed manufacturing and release testing of two lots of Phase 1 clinical drug product of SAB-142.

• Initiated in-vivo GLP juvenile toxicity safety and pharmacodynamic studies to enable Phase 2b clinical trial advancement to adolescent patients for SAB 142.

• Secured Fast Track Designation and Breakthrough Therapy Designation from FDA for SAB-176 for treatment and prophylaxis of influenza virus, providing an accelerated regulatory timeline for this asset as well as evidence of a clear regulatory strategy for all production system assets.

• Established proof-of-concept for our DiversitAb production system and Chemistry, Manufacturing and Controls (CMC) for multiple disease indications.

• Performed multiple clinical trials establishing the safety profile in >700 patients of hIgG produced in the DiversitAb production system and have demonstrated proof of clinical concept for our DiversitAb production system across three SAB-sponsored INDs and one CTA (filed in UK) that encompass seven clinical trials from Phase 1 to Phase 3 across treatment of three indications (MERS, Influenza, and COVID-19).

KEY PRODUCT DIFFERENTIATORS

Multivalent product platform to address complex diseases

Our unique production system harnesses the natural advantages of polyclonal immunoglobulins to protect against evolving disease targets by activating our body’s immune system in a target-specific way.

Our IgGs are engineered primarily to produce >90% of the IgG1 isotype with fully functional human antibody variable regions (or Fab domains) that specifically bind to target antigens, thus providing multivalent properties.

This multi-epitope capability can address individual variability of epitopes associated with immunological diseases and neutralize highly mutating targets, thus preventing mutation escape in infectious diseases.

There is a demonstrable and significant potential advantage of Tc Bovine-produced hIgGs characterized by their ability to bind to both foreign exogenous or human endogenous protein targets, ability to activate human effector cells, and do so in a way that does not cause serum sickness or anti-drug antibody formation.

Another key product differentiator of our platform is the ability to produce a multitarget product that addresses the complexity of disease in a single drug product vial.

This is a particularly powerful multivalent combination when multiple antigen targets are combined with the muti-epitope targeting of a single antigen (described above), as the therapeutic advantage is expanded to address multiple disease modalities all within a single vial.

Rapid Product Development Capability with Proven Regulatory Pathway

Our polyclonal development approach leverages our production system to capture discovery and production efficiencies not available to mAb product development.

Through the utilization of our Tc Bovine, we can simultaneously perform discovery and production functions of our polyclonal development, significantly improving the time of antibody discovery and production.

This efficiency was demonstrated during the COVID-19 pandemic where SAB-185 product that is in compliance with Current Good Manufacturing Practice regulations enforced by the FDA (cGMP), was produced in 90 days from initial product concept.

Our discovery process simply involves antigen design and production as the vaccinated Tc Bovine does the rest including antibody design, down selection, and scaled production all in one system.

Our regulatory pathway has also been established with the US FDA as well as MHRA in the United Kingdom and TGA in Australia.

The FDA regulates polyclonal hIgGs and mAbs differently, as mAbs are regulated through the Center for Drug Evaluation and Research (“CDER”) while pAbs are regulated by CBER.

CBER has approved over 36 IgG products from both human- and animal-derived plasma.

Further, CBER is very familiar with our DiversitAb production system and pAb product.

We have navigated three SAB drug products through seven clinical trials with one product having advanced to Phase 3.

PIPELINE PROGRAMS

SAB-142 HUMAN ANTI-THYMOCYTE GLOBULIN FOR TYPE 1 DIABETES

Summary of SAB 142 for T1D

SAB-142 is a first-in-class, human, multi-target anti-thymocyte globulin treatment designed to provide superior efficacy and safety in delaying the onset or progression of T1D.

We have optimized genetic engineering in the development of transchromosomic cattle, or Tc Bovine, which produce hIgG.

Our engineering of our production platform drives IgG1 production across our pipeline.

In addition, this differentiated approach using polyclonal antibodies has no biosimilar pathway, which provides a significant barrier to competitive polyclonal approaches.

Our Development Pipeline

The following table highlights our current development pipeline:

Our Lead Product Candidate

Our wholly owned lead product candidate, SAB-142 is a human anti-thymocyte globulin (ATG) focused on preventing or delaying the progression of T1D.

SAB-142 is a first-in-class, human, multi-target ATG treatment designed to provide superior efficacy and safety in delaying the onset or progression of T1D.

SAB-142 is expected to reduce autoimmune β-cell destruction and delay progression or onset of T1D in patients with Stage 3 or Stage 2 T1D, respectively.

The mechanism of action of SAB-142 has been clinically validated in numerous clinical trials with a rabbit anti-thymocyte globulin (rATG).

Data from more than 700 human subjects treated with antibodies produced by our platform support expectation of a zero serum sickness rate and zero incidence of neutralizing anti-drug antibodies (ADA) within the upcoming SAB-142 trials.

addition, data from more than 700 human subjects treated with antibodies produced by our platform support expectation of a zero-serum sickness rate and zero incidence of neutralizing anti-drug antibodies (ADA) within the upcoming SAB-142 clinical trials.

There is an established regulatory path for T1D indications using the SAB-142 modality.

We initiated the Phase 1 clinical study with the first patient dosed November 2023.

Finally, our next steps will be to file a clinical trial application (CTA) in the EU and an investigational new drug (IND) application in the United States to expand the clinical trials to global jurisdictions.

Type 1 Diabetes Background

Our regulatory pathway has also been established with the United States Food and Drug Administration (FDA) as well as United Kingdom Medicines and Healthcare products Regulatory Agency (MHRA) and Therapeutic Good Administration (TGA) in Australia.

The FDA regulates polyclonal hIgG and mAbs differently, as mAbs are regulated through the Center for Drug Evaluation and Research (CDER) while pAbs are regulated by CBER.

CBER has approved over 36 immunoglobulin products from both human- and animal-derived plasma.

Further, CBER is very familiar with our production platform and pAb products.

We have navigated three SAB drug products through seven clinical trials with one product having advanced to Phase 3, building our safety database as well as positive efficacy data.

As our lead program SAB-142 advances, we intend to expand our pipeline in complementary indications through strategic utilization of our platform.

We recently received an Investigational New Drug (IND) clearance from the FDA in May 2024 and announced positive topline data from our Phase 1 clinical trial of SAB-142 in January 2025.

Next, we intend to advance SAB-142 into a Phase 2b clinical trial called the SAFEGUARD study which is anticipated to initiate mid-year 2025.

Background On Type 1 Diabetes

High Prevalence in Type 1 Diabetes

T1D is a complex and life-threatening autoimmune disease in which the body mistakenly attacks the insulin-producing beta cells of the pancreas.

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From a drug development perspective, shifting away from chronic disease management and towards disease-modifying therapies has the potential to change and save millions of lives.

• According to the T1D Index, a global data simulation tool launched by Juvenile Diabetes Research Foundation (“JDRF”) in 2022, the prevalence of T1D has increased at four times the rate of population growth in every country across the globe since 2000.

• According to the T1D Index, a global data simulation tool launched by Breakthrough T1D Foundation, formerly known as the Juvenile Diabetes Research Foundation (JDRF), in 2022, the prevalence of T1D has increased at four times the rate of population growth in every country across the globe since 2000.

• Nearly 1 in 300 children in the United States will be diagnosed with T1D during childhood, and one in every seven healthcare dollars can be attributable to the cost of managing diabetes over the lifetime.

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According to these estimates, T1D stands to become one of the world’s largest deadly chronic health conditions, similar in scale and impact to HIV.

Therapeutic Potential of the Polyclonal Modality in New-Onset Type 1 Diabetes

Maintenance of the level of connecting peptide, a short 31 amino acid polypeptide that connects insulin’s A chain to its B chain in the proinsulin molecule, commonly referred to as C-peptide, is a validated surrogate endpoint for endogenous insulin production, essential for the prevention of progression of T1D.

Placebo controlled trials with low-dose rATG, defined as a single dose of 2.5 milligram per kilogram (mg/kg), have shown statistically significant maintenance of C-peptide levels and thus a delay in progression of recent onset T1D.

Current Type 1 Diabetes Treatment Landscape and Their Limitations

Despite significant advances in diabetes technology which has enabled those with T1D mellitus to manage and improve their metabolic control, there remains a significant unmet need in this therapeutic area and the patient burden and potential for acute complications remains high.

Insulin injection is the current standard of care for T1D, yet self-management of T1D involves complex daily routines and careful monitoring of dietary intake and activity levels to potentially achieve glycemic targets associated with a reduced risk of long‐term diabetes complications.

Insulin pumps featuring a computerized system for sensing blood glucose to deliver an appropriate dose of insulin have been frequently reported to the FDA for problems.

A high incidence of failure in achieving glycemic targets is a consistently reported issue.

Additionally, long term complications of the disease include a reduced life expectancy of 10-15 years, and significant acute complications such as hyperglycemia, including diabetic ketoacidosis, premature myocardial infarction, stroke, limb ischemia, gangrene, kidney failure, blindness due to diabetic retinopathy, coma and potentially death.

All current therapies require patients to carefully monitor their dietary intake, which is inconvenient in adults and a frequent point of failure in adolescents and children.

Pancreas transplantation for uncontrolled diabetes was first performed in the 1960s and established the principle that replacing the beta cells could restore physiological glucose control.

Pancreas transplants are limited due to the availability of organs, complicated surgical interventions, and require lifelong immunosuppression.

Despite its limitations, approximately 30,000 pancreas transplants have been performed worldwide to date.

Several existing treatment options for T2D have been investigated to treat T1D, though generally without success.

While SGLT-1/2 and SGLT-2 inhibitors were initially approved in Europe and Japan with label restrictions to certain sub-groups of patients with T1D, and continue to be approved for patients with T2D, these therapies have since been withdrawn from the European market and have not received regulatory approval in the U.S.

for T1D due to safety risks primarily related to the risk of diabetic ketoacidosis.

Pramlintide (Symlin), an amylin peptide analog approved for mealtime injections, has been approved for use in both T1D and T2D since 2005 but has not been adopted widely.

Other therapeutic modalities, including monoclonal antibodies, are under clinical investigation and have demonstrated evidence of the potential to delay the onset of T1D.

In November 2022, the FDA approved Tzield (teplizumab), a humanized anti-CD3 monoclonal antibody for the treatment of patients with two or more diabetes-related auto-antibodies to delay the onset of T1D.

However, as with any autoimmune disease, a single treatment such as Tzield cannot address the entire spectrum of the unmet need of patients with Stage 1-4 T1D due to the significant heterogeneity of the disease, where every patient may not respond to the therapy.

Currently, Tzield is approved in the U.S.

only for patients with Stage 2 T1D and has been filed for approval in Europe for patients with Stage 3 T1D.

In addition, the treatment burden for Tzield for Stage 2 and Stage 3 T1D is one course of intravenous (IV) daily therapy for 12 days at Month 1 and two courses of IV daily therapy for 12 days, at Month 1 and Month 6, respectively.

Teplizumab also has an immunogenicity liability.

Of patients treated with Teplizumab, 57% had ADAs, 46% of which were neutralizing ADAs.

There are currently no approved therapies in delaying the progression of T1D in new-onset Stage 3 T1D patients, thus significant unmet medical needs remain for the development of therapies that target specific patient needs across various stages of T1D diagnosis.

New onset Stage 3 T1D is the first indication we plan to pursue with SAB-142, as we continue our work to change the lives of people impacted by T1D through unique disease-modifying therapies.

Clinical Validation of Anti-Thymocyte Globulin in New Onset Type 1 Diabetes

Maintenance of the level of connecting peptide (C-peptide), a short 31 amino acid polypeptide that connects insulin’s A chain to its B chain in the proinsulin molecule, is a validated surrogate endpoint for endogenous insulin production, essential for delaying progression of T1D.

Placebo controlled trials with low-dose rATG, defined as a single dose of 2.5 milligram per kilogram (mg/kg) administered intravenously over two days in an ambulatory setting, have shown statistically significant maintenance of C-peptide levels and thus a delay in progression of recent onset T1D.

Based on the results of a Phase 2 clinical trial conducted at the University of Florida, a single dose of rATG showed sustained benefit in T1D over a two-year period by maintaining significantly higher C-peptide levels than a placebo control.

However, more than 65% of treated patients in this study acquired serum sickness due to the infusion of a non-human antibody, with symptoms that included rash, malaise, fever, and joint swelling.

The symptoms often required treatment with steroids that control serum sickness but impair diabetes management and reduces the capacity to re-dose rATG when C-peptide levels begin to drop as shown in Figure 2 below.

Rabbit ATG Study for Type 1 diabetes

Comparison Efficacy of SAB-142 to rATG

The journey for a polyclonal antibody began over 15 years ago when the first preclinical study demonstrating efficacy of rabbit anti-thymocyte globulin (rATG, Thymoglobulin) in non-obese diabetic (NOD) mice was performed.

Since then, groundbreaking clinical trials with rabbit ATG have been conducted in patients with a recent T1D onset diagnosis.

Rabbit ATG, as shown in Figure 1 below, has shown potential therapeutic benefit in T1D as a multi-target polyclonal antibody known to bind multiple lymphocyte cell markers likely associated with this mechanism of action in the modulation of the immune system.

Multi-Target Binding of Thymoglobulin (rATG) IgG Polyclonal Immunoglobulin

All antibody products targeting human proteins have the potential for on-target or off-target adverse effects.

Figure 3 below summarizes an indicative safety assay, showing that compared to rATG, SAB-142 has a potentially better safety profile as much more of the SAB-142 antibody is required to have the same red blood cell binding activity as the FDA-approved rATG.

We have also shown in the table to the right that SAB-142 has potentially higher potency relative to rATG as measured by complement-dependent cytotoxicity activity, using human complement.

SAB-142 has Potential for a Best-in-Class Safety Profile with Higher Potency Compared to FDA Approved rATG (Thymoglobulin)

To characterize the multi-target binding profile of SAB-142, we compared the target-specific binding profile of SAB-142 to rATG against CD markers associated with human lymphocytes.

The data shows similar targeted binding activity between SAB-142 and rATG to the CD2 cell marker associated with human lymphocytes.

Figure 4 below illustrates SAB-142’s similar binding profile to T-cell subsets compared to rATG.

This in-vitro flow cytometry data shows SAB-142 on the X-axis binding to the exact same human T-lymphocyte, T helper cells and cytotoxic T-cell populations as rATG on the Y-axis.

SAB-142 Demonstrates Similar T-Cell Subset Binding Profile as rATG

We further demonstrated that SAB-142 has a similar mechanism of action associated with T-cell subsets compared to rATG shown in Figure 5 below.

Similar to rATG, SAB-142 induced a significant reduction of live cytotoxic CD8+T-cells in a dose-dependent manner compared to the non-target-specific human IgG control.

Furthermore, SAB-142 activated the

conversion of naïve CD4+ cells to an activated state and most importantly, preserved T regulatory cells, again, similar to rATG.

As the data shows, SAB-142 demonstrated a multi-target binding profile and mechanism of action similar to FDA-approved rATG with the potential of an improved safety profile and potency.

SAB-142 Demonstrates Similar T-Cell Subset Mechanism of Action as rATG

However, more than 65% of treated patients in this study reported serum sickness due to the infusion of a non-human antibody, with symptoms that included rash, malaise, fever, and joint swelling, with over 50% of those subject developing serum sickness of Grade 3-4 (severe and life-threatening according to the CTCAE criteria).

The symptoms often required treatment with steroids that control serum sickness but impair diabetes management and reduces the capacity to re-dose rATG when C-peptide levels begin to drop.

The below graph shows the statistically significant preservation of C-peptide (p=0.00005) over two years in low dose rATG.

The following table highlights the C-peptide response of anti-thymocyte globulin:

Low-Dose ATG* Preserved C-Peptide in New Onset T1D

In addition to the C-peptide data, rATG treated patients showed a significant reduction in glycated hemoglobin A1C (HbA1C) over the placebo group (p=0.002).

A review of safety parameters based on both short and long-term safety data (up to five years from three separate clinical trials conducted with low-dose rATG in Stage 3 T1D patients) highlights that safety issues associated with dosing humans with rabbit-derived antibodies are predominantly focused on the serum sickness, high immunogenicity, and CD4+ sustained lymphodepletion.

These side effects appear to be dose-dependent, with the higher dose level of rATG at 6.5mg/kg having higher proportion of participants with the AEs.

Nevertheless, at low dose levels, this mechanism of action (MoA) is proven to be immunomodulatory rather than immunosuppressive.

Three studies were conducted with two doses of rATG:

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Finally, none of the three trials observed an increase in liquid cancers or solid malignancies.

In summary, the overall long-term safety profile of a low-dose ATG is supportive of the vision to use SAB-142 as a lifelong disease-modifying treatment without a risk of immunosuppression associated with clinically significant effects such as infections, malignancies or suppressed humoral response.

Comparative MoA and Administration of rabbit ATG and SAB-142

Rabbit ATG shows therapeutic promise but offers problematic potential for adverse events that could inhibit long term disease modification and redosing;

we believe those issues are resolved by SAB-142.

SAB-142 represents an opportunity to offer a novel human alternative to rabbit- or equine-derived ATG IgGs with potential for safe and reliable re-dosing while avoiding the risk factors observed with currently available therapies.

While the mechanism of action of our compound closely resembles rATG, SAB-142 has clear advantages that are fundamental for safe and reliable re-dosing required to delay disease progression.

It is well established that treatment with heterologous proteins such as rATG can result in serum sickness, which can trigger Grade 3 adverse events.

Limitations to Rabbit Anti-Thymocyte Globulin

Rabbit ATG shows therapeutic promise but its heterologous nature and high immunogenicity are problematic given adverse events that could inhibit long term disease modification and redosing.

It is well established that treatment with heterologous proteins such as rATG can result in serum sickness, which can trigger Grade 3 or higher adverse events.

Serum sickness is defined as a Type 3 hypersensitivity reaction.

The heterologous nature of rATG also results in the production of neutralizing anti-drug antibodies (ADAs) in the majority of patients even after a single course of therapy.

Neutralizing anti-drug antibodies, or NAbs, are a subset of ADAs that bind to the drug and inhibit its pharmacologic action or activity.

The heterologous nature of rATG also results in the production of neutralizing ADAs in most patients even after a single course of therapy.

Neutralizing ADAs, or NAbs, are a subset of ADAs that bind to the drug and inhibit its pharmacologic action or activity.

Once pharmacological function is inhibited, beta cells are left unprotected from attacks by the cytotoxic CD8-positive T-cells or inflammatory mediators, and the disease continues to progress.

Our Solution for Type 1 Diabetes

SAB-142 is a first-in-class, human, multi-target ATG treatment designed to provide superior efficacy and safety in delaying the onset or progression of T1D and offers a novel human alternative to rabbit- or equine-derived ATG with potential for safe and reliable re-dosing while eliminating the treatment burden observed with currently available therapies.

While the MoA of our compound closely resembles rATG, SAB-142 has clear advantages that are fundamental for safe and reliable re-dosing required to delay disease progression.

Data from preclinical studies and clinical trials suggest that commercially approved rATG has been shown to transiently restore immune-tolerance and reduce autoimmune attack on pancreatic beta cells in T1D patients.

Following IV administration, both rATG and SAB-142 have been shown to target key circulating immune cell types involved in an autoimmune response in T1D.

Both ATGs cause a dose-proportional transient reduction of CD4+ and CD8+ T-cells while sparing T regulatory (Treg) cells in addition to modulating other autoimmune pathways involved in T1D pathophysiology.

These include macrophages and B cells.

administration, both rATG and SAB-142 have been shown to target key circulating immune cell types involved in an autoimmune response in T1D.

Both ATGs cause a dose-proportional sustained exhaustion of CD4+ and CD8+ T-cells while sparing T regulatory (Treg) cells in addition to modulating other autoimmune pathways involved in T1D pathophysiology.

By reducing overreactive CD4+ and CD8+ T cells while preserving T reg cells, SAB-142 is expected to reduce autoimmune β-cell destruction and delay progression or onset of T1D in patients with Stage 3 or Stage 2 T1D respectively.

In addition to potentially preserving beta cell function in early T1D patients, SAB-142 offers the potential of re-dosing when examining clinically meaningful indicators such as C-peptide levels and glycosylated hemoglobin (HbA1c), without the potential risk of inducing major immune reactions of animal derived IgGs.

A short-term safety signal observed in these clinical trials includes serum sickness (SS) and cytokine release syndrome (CRS).

In all three trials with rATG, cytokine release syndrome (CRS) was observed.

However, its incidence appears to be dose dependent.

Comparative Efficacy of teplizumab and SAB-142

Teplizumab, sold under the brand name Tzield, is a humanized anti-CD3 monoclonal antibody that is the first approved treatment indicated to delay the onset of 2 T1D.

Teplizumab was approved by the FDA in November of 2022 and is the first approved disease-modifying drug for T1D.

To complete a comparative profile of the SAB-142, it is important to understand how it could be benchmarked against teplizumab, a humanized monoclonal antibody.

Teplizumab exclusively binds to the CD3 receptor on T-cells, while the mode of action for SAB-142 is multifactorial, binding to multiple T cell receptors associated with various lymphocyte subsets.

Teplizumab is currently approved in a single indication, Stage 2 T1D.

With SAB-142, we are targeting both Stage 2 and Stage 3 T1D patients.

(See Figures 6 and 8 ) It is anticipated that Sanofi may file a supplemental NDA with the US FDA for approval for use in patients with Stage 3 T1D.

Based on the published peer-reviewed analysis, teplizumab showed a 63% effect on C-peptide AUC after year two, whereas rATG showed 103% effect on C-peptide AUC at year two.

Teplizumab also has immunogenicity liability.

Of patients treated with teplizumab, 57% had ADAs, 46% of which were neutralizing ADAs.

Due to the human nature of SAB-142, the probability of ADA or neutralizing ADA is very low, which is supported by the immunogenicity data from our clinical trials.

Lastly, teplizumab is administered intravenously with a daily IV required over 12-14 days, while SAB-142 dosing is expected to be administered over one to two days.

Comparative MoA and Administration of teplizumab and SAB-142

SAB-142 Comparison with Teplizumab (Tzield)

Manufacturing of SAB-142

To produce SAB-142, we strategically focused on making a best-in-class, human, anti-thymocyte globulin.

To accomplish this, we focused our development on improving both the potency and safety profile of SAB-142 benchmarked against FDA-approved rATG or Thymoglobulin .

Recapitulating the rATG mechanism of action was anticipated as the production process of SAB-142 is nearly identical to rATG, wherein the wild-type rabbits are vaccinated with human thymocytes which mount a rabbit polyclonal response.

These antibodies are subsequently purified from the plasma ( Figure 7 ).

SAB uses a similar production process where we also vaccinate our Tc Bovine with human thymocytes.

However, instead of producing animal polyclonal antibodies, our production system produces human anti-thymocyte globulin, which elicits a mechanism of action similar to that of rATG.

According to our estimates, between 15-20 Tc bovine could produce tens of thousands of doses of SAB-142.

SAB-142 Production Similar to FDA Approved rATG

Indication and Clinical Strategy for SAB-142

In addition to potentially preserving beta cell function in early T1D patients, SAB-142 offers the potential of safe and reliable re-dosing when examining clinically meaningful indicators such as C-peptide levels and HbA1c, without the potential risk of inducing major immune reactions of animal derived immunoglobulins.

In the first-in-human Phase 1 clinical trial SAB-142-101, SAB-142 demonstrated zero serum sickness and zero immunogenicity at the target dose levels, thus supporting its potential for safe and reliable redosing.

Clinical Strategy for SAB-142

Immunological processes resulting in the breakdown of self-tolerance and gradual destruction of pancreatic beta cells by the patient’s own immune system preceding the clinical onset of disease oftentimes starts very early in patients’ lives, sometimes as early as in utero.

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Unfortunately, when an individual is first diagnosed with clinical stage T1D, 50- 90% of pancreatic insulin-producing beta cells are already destroyed.

Hence, it is critical to start therapy that preserves the remaining fully functional beta cells as soon as possible as it may provide the highest benefit throughout the patient’s lifetime (see Figure 8 ).

SAB-142 has Strong Potential to Control or Prevent T1D Over the Entire Life Span

One of the early proposed studies in our clinical development program will be in those patients with Stage 3 T1D.

The trial participants will be patients who are recently diagnosed with the disease.

Hence, it is critical to start therapy that preserves the remaining fully functional beta cells as soon as possible as it may provide the highest benefit throughout the patient’s lifetime.

The table below illustrates the therapeutic landscape of T1D and its disease continuum.

T1D Disease Continuum

As referenced in the above illustration, one of the early proposed studies in our clinical development program will be in those patients with newly diagnosed Stage 3 T1D.

Following the trials in Stage 3, we would progress into clinical trials in Stage 2 patients.

Stage 2 patients are those who do not yet have a full clinical onset of T1D and have even more functional beta cells that can be further preserved.

In this patient population, we will aim to delay the onset of full clinical T1D along with evaluation of the re-dosing potentially aimed at fully preventing clinical onset of disease.

Stage 2 patients are those who do not yet have a full clinical onset of T1D and have functional beta cells that can be further preserved.

In this patient population, we will aim to delay the onset of Stage 3 clinical T1D along with evaluation of the re-dosing potentially aimed at fully preventing clinical onset of disease.

The ultimate vision for SAB-142 is founded on the potential ability to safely re-dose by delivering a consistent and effective dose of this medication only once per year to fully halt progression of established clinical disease or delay its onset indefinitely.

Preclinical Studies for SAB-142

We have completed the GLP toxicology study that enables filing an IND submission.

• Determine the potential toxicity of SAB-142 vs.

an anti-thymocyte globulin (ATG) when given by single intravenous infusion to non-human primates.

• Characterize mechanism of action, toxicokinetic and immunogenicity profile of SAB-142.

• GLP toxicology study demonstrated SAB-142 is well tolerated at escalating doses tested.

• Both SAB-142 and rATG induced transient dose-proportional change in lymphocytes with dose-dependent recovery to baseline.

The dynamics of such depletion appears to be more prolonged with SAB-142 treatment in a dose-dependent manner.

This data demonstrates the power of our multi-target approach, which is currently only possible with our production system, where SAB-142 directly impacts each individual immune cell subset.

These in vivo results suggest that SAB-142 may have pharmacokinetic and pharmacodynamic attributes relevant for disease-modifying effects in T1D while having the impactful product advantage of an improved safety profile.

IND/CTA filings are anticipated by fourth quarter 2024.

SAB-142 GLP Toxicology Study Results Shows Impacts on Major Relevant T-cell Subsets in-vivo Enables IND Submission

Additionally, we have started a GLP juvenile toxicology study in non-human primates that will read out in the second half of 2024 to enable inclusion of adolescent T1D patients in the future Phase 2b study of SAB-142.

Clinical Trial Design and Timelines

Our Phase 1 trial is a randomized, double-blind, single ascending dose trial to assess safety, tolerability, pharmacokinetics, pharmacodynamics, and proof of biological activity (POBA) of SAB-142 for T1D indications (See Figure 10 ).

We commenced dosing in healthy volunteers in November of 2023.

The proposed dose range for SAB-142 is projected to be a single infusion over two days ranging between 0.03 and 2.5 mg/kg.

We believe major outcomes from this Phase 1 trial will include validating SAB-142 potential for safety superiority based on an anticipated 0% serum sickness and 0% neutralizing anti-drug antibody.

We also believe the study will validate the mechanism of action of SAB-142 in humans and establish proof of biological activity based on the change versus baseline in the most important cell lineages such as CD3, CD4, CD8-positive T-cells and Tregs vs.

those of rATG in a cross-study comparison.

SAB-142 Phase 1 Clinical Plan

In addition to the currently approved and ongoing Phase 1, we plan to bring this program to IND and CTA filings with global regulatory authorities by the mid-2024.

As there are unmet medical needs globally for disease-modifying treatments of T1D, we plan to work with global health authorities and file clinical trial applications and clinical trial notifications in other countries to have a global footprint and reach patients with T1D worldwide.

We anticipate topline results by the end of 2024.

Topline data will include the safety data to support re-dosing along with proof of biological activity.

Topline data will further enable global Phase 2 clinical proof of concept and dose-range finding trials in adults and even more importantly, in adolescent T1D population, another critical milestone for 2024 as T1D onset most often occurs in pediatric and adolescent patient populations.

Figure 11 shows a proposed timeline of our planned milestones in the next 24 months.

SAB-142 Timeline and Key Milestones

SAB-176 HUMAN ANTI-INFLUENZA GLOBULIN FOR HIGH-RISK INFLUENZA

Summary of SAB-176

SAB-176 is a multivalent, broadly neutralizing -human polyclonal IgG therapeutic candidate in development for the treatment or prevention of severe influenza.

This novel, specifically targeted high-potency immunotherapy leverages the human immune response and is designed to bind and neutralize both Type A and Type B influenza, including emerging and mutating strains.

It may also be modified to address annual strain changes when needed.

Nonclinical and clinical data suggests that SAB-176 offers broad protection against diverse influenza strains, even those that were not specifically targeted, potentially because of its strong cross-reactive potencies to conserved epitopes.

We have completed multiple clinical and nonclinical studies to date, including a Phase 1 trial in healthy volunteers, and most recently a Phase 2a challenge study that was initiated in June 2021.

SAB-176 has the potential to complement seasonal vaccine programs to achieve better efficacy than small molecule anti-influenza antivirals in the general population, avoid development of resistant strains, and serve as a protective prophylactic in high-risk populations.

We believe that this promising therapy is well-suited to address highly mutating viruses that have significant annual health impacts as well as pandemic potential.

Intravenous, sub-cutaneous, and intra-muscular routes of administration are in development for this product.

Influenza Background

Despite numerous available vaccines and treatments, influenza remains a disease with high-unmet medical need, accounting for ~500,000 cases, ~30,000+ deaths, and $11.2 billion dollars per year in direct and indirect costs in the US alone.

Only ~50% of high-risk patients vaccinate, and even when vaccines are used, CDC reports adjusted vaccine effectiveness (VE) ranged from only 10% to 60% from 2004 through 2022, with 60% reported only in a single season.

Immunocompromised/immunosenescent patients show even lower levels of response to vaccines, with VE at ~24%.

No approved treatment of influenza showed any efficacy in hospitalized patients and viral mutations result in reduced susceptibility or resistance to current treatments.

Seasonal influenza remains a meaningful burden for the healthcare system.

While the influenza season differs each year, the CDC estimates there are on average 9 to 41 million cases of influenza each year, with 140,000-710,000 hospitalizations and

12,000-52,000 deaths per year (average 2010-2020).

Oseltamivir phosphate (branded:

Tamiflu®) is an effective therapy for treating the flu if used within two days of onset.

However, some patients still develop severe disease and are resistant to treatment (estimates of resistance vary:

As such, we see the potential for an additional treatment for flu, particularly in higher-risk patients.

Competition and SAB-176 Value Proposition

Only SAB-176 Provides Potential for Influenza Biologic with Low Risk of Escape Mutants

SAB-176 represents a comprehensive approach to treatment and prophylaxis (PreP and PEP) of high-risk patients with influenza as a broadly neutralizing -human polyclonal immunoglobulin therapeutic with several anti-viral mechanisms.

To summarize, a few key differentiation aspects of this asset include a multi-pronged approach by neutralizing the virus directly and by inducing Antibody Dependent Cellular Cytotoxicity (ADCC), coupled with a long half-life aimed at providing an extended protection against viral shedding and recrudescent infection, low risk of antiviral resistance/escape mutants, and potential to treat patients infected with anti-viral resistant strains.

( See Figure 12 ) .

Phase 2a Challenge Trial

In December 2021, we announced topline data for a Phase 2a challenge trial that was initiated in June 2021.

This was a randomized, double-blind, placebo-controlled study evaluating the safety and treatment efficacy of SAB-176 in 60 healthy adults challenged with a pandemic influenza virus strain (pH1N1).

Participants were randomized to receive either SAB-176 (25 mg/kg dose) or placebo and were intranasally inoculated with pandemic H1N1 (2009/California) virus.

Nasopharyngeal swabs were taken 8 days after inoculation.

The primary endpoint of the study was reduction of the nasopharyngeal viral load of subjects treated with SAB-176 (expressed as area under the curve, or AUC) compared to those receiving placebo over an 8-day timepoint as measured by qRT-PCR.

SAB-176 met the primary endpoint of significantly reducing patient pH1N1 influenza viral load in the treated subjects (p = 0.026, one sided).

Phase 2a Double-Blind, Placebo-Controlled Study

Secondary endpoints produced similar results, showing separation of SAB-176 vs placebo.

One of the secondary endpoints of the challenge study was reduction of clinical flu signs and symptoms in the subjects receiving active treatment (n=8) compared to placebo controls (n=12) for those who had signs and symptoms.

SAB-176 achieved statistical significance in meeting the secondary endpoint at Day 4 (p = 0.013, one sided) in symptomatic patients.

In this study, SAB-176 also appeared to be safe and well tolerated.

No SAB-176-related serious adverse events (SAEs) were observed, and most adverse events were mild to moderate.

Phase 1 Trial

SAB-176 was evaluated in an ascending dose, double-blind, randomized, placebo-controlled Phase 1 safety trial in 27 healthy volunteers in 2020.

The FDA allowed us to initiate a Phase 1 trial in healthy adults based on the safety profile in the preclinical data set.

A Safety Review Committee (SRC) monitored adverse events after each cohort was infused and recommended that each later cohort could be infused with the next highest dose according to the study protocol.

Although anticipated adverse events were noted among the SAB-176 and placebo participants, no drug related SAEs were identified by the SRC.

Proprietary DiversitAb Production System Overview

Our proprietary DiversitAb production system gives us the unique ability to generate targeted, human IgGs without the need for human donors or plasma.

These diverse and high-potency hIgGs can be targeted to human immunogens for immune disorders or cancer, viruses, bacteria, and toxins.

The production system relies on advanced genetic engineering that functionally replaces bovine IgGs with human hIgGs (resulting in our Tc Bovine) produced from the full germ-line repertoire of human antibody heavy chain and kappa light chain genes on an engineered human artificial chromosome (HAC).

The human antibody genes have been further engineered to efficiently produce a diverse repertoire of human immunoglobulin G (which is referred to as hIgG) in bovine B-cells in response to specifically targeted immunogens as a result of the hyperimmunization of the Tc Bovine.

Bovine were selected because they are large animals that produce large amounts of plasma, and as ruminants, have high concentrations of circulating hIgGs with a robust response to immunogen challenge that produces high potency, high avidity hIgGs.

Through our DiversitAb production system, we have engineered a targeted human immunoglobulin production system that emulates the way that the human immune system synergistically targets the complexity of human disease.

Clinical Development of SAB-142

On January 28, 2025 we announced positive topline phase 1 clinical results with the Company’s potentially disease-modifying T1D therapy SAB-142.

Based on the data, we plan to advance SAB-142 into a Phase 2b trial in 2025 to evaluate the therapeutic candidate in adult and pediatric patients with new-onset T1D.

The SAB-142 Phase 1 clinical trial was designed as a randomized, double-blind, placebo-controlled, single-ascending dose, adaptive design clinical study among healthy volunteers and one cohort of participants with T1D that commenced dosing in November 2023.

The objectives include establishing the safety, tolerability, pharmacokinetic (PK), immunogenicity and pharmacodynamic (PD) profile for SAB-142.

The reported topline results showed the following outcomes among healthy volunteer cohorts:

• 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 ADAs.

• Sustained Immunomodulation:

SAB-142 demonstrated a clinically validated multi-target MOA with sustained immunomodulation.

• Mechanism of Action Analogous to Rabbit ATG:

The MOA of SAB-142 was shown to be analogous to rabbit ATG.

The SAB-142 MOA was shown to be analogous to rabbit ATG across multiple parameters correlative to C-peptide preservation.

Based on the completed Phase 1 clinical trial, we plan on initiating a global Phase 2b study, SAFEGUARD ( SAF ety and E fficacy of human anti-thymocyte immuno G lob U lin SAB-142 AR resting progression of type 1 D iabetes), which would be a randomized, double blinded, placebo controlled, dose ranging study in new onset pediatric, adolescent and adult Stage 3 T1D patients.

The primary endpoint is stimulated C-peptide following a 2-hour mixed meal tolerance test (MMTT) at 12 months and secondary endpoints are time in range, time in tight Range, time below range, prandial insulin use, HbA1c, hypoglycemic episodes and safety.

This Phase 2b study is expected to initiate in the middle of 2025 with interim data in the middle of 2026 and topline data in 2027.

Other Immunology Indications

T- and B-cells are multifunctional lymphocytes whose dysregulation was shown to have a central role in the pathogenesis of more than 80 autoimmune diseases, including T1D, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS) and celiac disease.

The therapeutic success to date of lymphocyte- mediating therapies in variety of autoimmune diseases and our in vivo and in vitro pre-clinical and Phase 1 work from SAB-142 in T1D will support direct progression into Phase 2 clinical trials in other autoimmune indications.

Proprietary Production Platform Overview

Our proprietary production platform gives us the unique ability to generate targeted, hIgG without the need for human donors or plasma.

Diverse and high-potency hIgG can be targeted to human immunogens for immune disorders or cancer, viruses, bacteria, and toxins.

The production system relies on advanced genetic engineering that functionally replaces bovine immunoglobulin with hIgG (resulting in our Tc Bovine) produced from the full germ-line repertoire of human antibody heavy chain and kappa light chain genes on an engineered human artificial chromosome (HAC).

The human antibody genes have been further engineered to efficiently produce a diverse repertoire of hIgG in bovine B-cells in response to specifically targeted immunogens as a result of the hyperimmunization of the Tc Bovine.

Bovine were selected because they are large animals that produce large amounts of plasma, and as ruminants, have high concentrations of circulating hIgG with a robust response to immunogen challenge that produces high potency, high avidity hIgG.

Through our production platform, we have engineered a targeted hIgG production platform that emulates the way that the human immune system synergistically targets the complexity of human disease.

The discovery, development and production process represent a “plug-and-play” approach:

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An immunogen is developed for a specific target in much the same that human vaccines are developed.

The production system is designed to address virtually any target including

bacteria (whole killed), viruses, toxins, nucleic acids (i.e., RNA and DNA vaccines), whole cells, and human tissues.

The production platform is designed to address virtually any target including bacteria (whole killed), viruses, toxins, nucleic acids (i.e., RNA and DNA vaccines), whole cells, and human tissues.

• Hyperimmunize Tc Bovine .

Tc Bovine are genetically engineered to produce human IgGs.

They are then hyperimmunized with the desired immunogen, driving the immune response beyond protective levels that have been shown in some cases to be 40-60 times more potent than hIgGs produced in convalescent patients.

Tc Bovine are genetically engineered to produce hIgG.

• Collect Plasma .

The target specific human IgGs are collected from the Tc Bovine by plasma donations.

• Isolate Human IgGs .

Human IgGs are then isolated from the plasma through a well-established plasma fractionation process and Quality Control tested.

These IgGs are then ready for use as a human immunotherapy treatment or prophylactic.

Our DiversitAb production system is replicable and scalable given Tc Bovine are genetic clones.

Animals can be produced through cloning technology and plasma fractionation to meet market demand through a well-established and scalable GMP process.

We believe that targeted human IgGs can be produced against the same immunogen or multiple immunogens, depending on the disease target and indication, in as many Tc Bovine as necessary to generate sufficient doses to fully supply the target market.

Human IgG consistency of product is achieved by testing the potency of IgGs contained in each plasma collection and then combining plasma collections in a manufacturing pool that generates specified potencies within a specified antibody protein concentration.

We believe that the speed with which we can deploy our DiversitAb production system to develop countermeasures for emerging diseases and pandemics represents a significant advantage relative to other antibody manufacturers.

We have successfully utilized our DiversitAb production system technology to generate early proof of concept and initial clinical lots that address specified immunotherapy targets in as little as 128 days, including completion of IND-enabling studies, in response to the COVID-19 pandemic.

The target specific hIgG is collected from the Tc Bovine by plasma donations.

• Isolate hIgG .

hIgG is then isolated from the plasma through a well-established plasma fractionation and purification process and Quality Control tested.

This highly purified hIgG is then ready for use as a human immunotherapy treatment or prophylactic.

Our production platform is replicable and scalable given Tc Bovine are genetic clones.

Animals can be produced through cloning technology and the plasma fractionation process scaled to meet market demand through a well-established GMP process.

We believe that targeted hIgG can be produced against the same immunogen or multiple immunogens, depending on the disease target and indication, in as many Tc Bovine as necessary to generate sufficient doses to fully supply the target market.

Consistency of hIgG product is achieved by testing the potency of hIgG contained in each plasma collection and then combining plasma collections in a manufacturing pool that generates specified potencies within a specified antibody protein concentration.

Manufacturing Strategy

In support of our operations, we currently operate two plasma fractionation purification facilities in Sioux Falls, South Dakota:

a 50L small batch scale cGMP suite that has produced clinical grade drug product to accommodate Pre-Clinical and Phase 1 studies, and a 200L scale larger batch cGMP suite that was completed in 2021 which can be used to produce clinical grade drug substance and drug product to accommodate larger sized advanced Phase 2 clinical studies or Emergency Use.

In support of our operations, we currently operate two plasma fractionation and purification facilities in Sioux Falls, South Dakota:

a 50L small batch scale cGMP suite that has produced clinical grade drug product to accommodate Pre-Clinical and Phase 1 studies, and a 200L scale larger batch cGMP suite that was completed in 2021 which can be used to produce clinical grade drug product to accommodate larger sized advanced Phase 2 clinical studies or Emergency Use scale.

In addition, we maintain supportive laboratory facilities and operations in Sioux Falls, South Dakota, for drug discovery, product and process development, and clinical manufacturing.

We have fully GLP and cGMP compliant quality control testing facilities and we have further developed our own internal antigen (immunogen) discovery and production capabilities to accommodate the Tc Bovine immunizations that improve our overall plasma production speed and efficiency further enhancing our drug discovery and clinical manufacturing timeline.

Our Tc Bovine are housed at dedicated specialty facilities, accredited by the American Association for Accreditation of Laboratory Animal Care (the “AAALAC”) that cater to the production, health, safety, and welfare of the animals, and provide plasma production.

We recently completed an expansion of our research and development laboratory facilities to accommodate our discovery programs, support for our pre-clinical pipeline programs, and process development research for our product candidates.

The upstream process is easily scalable.

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We believe our scientific knowledge, technology, and development capabilities provide us with substantial competitive advantages, but we face potential competition from multiple sources, major pharmaceutical, specialty pharmaceutical and existing or emerging biotechnology companies, academic research institutions, governmental agencies, and public and private research institutions worldwide.

We consider the following companies to be among our competitors or future competitors Sanofi S.A., Sana Biotechnology, Imcyse, vTv Therapeutics, IM Therapeutics, Sernova, and Biomea Fusion.

Our competitors may have significantly greater financial resources, robust drug pipelines, established presence in the market and expertise in research and development, manufacturing, pre-clinical and clinical testing, obtaining regulatory approvals and reimbursement and marketing approved products than we do.

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If any future product candidates identified through our current lead programs are eventually approved for sale, they will likely compete with a range of treatments that are either in development or currently marketed for use in those same disease indications.

Our success will partially depend on our ability to obtain, maintain, enforce, and defend patents and other intellectual property rights with respect to our hIgGs that are proven to be safer or more effective or are less expensive than competing products.

Our success will partially depend on our ability to obtain, maintain, enforce, and defend patents and other intellectual property rights with respect to our hIgG that are proven to be safer or more effective or are less expensive than competing products.

We could see a reduction or elimination in our commercial opportunity if our competitors develop and commercialize drugs that are safer, better tolerated, more effective, more convenient to administer, less expensive, more resistant to viral escape, or receive a more favorable label than our product candidates.

Intellectual Property

We actively seek to protect the intellectual property and proprietary technology production system that we believe is important to our business, which includes seeking and maintaining patents covering our technology production system and products, and any other inventions that are commercially or strategically important to the development of our business.

We actively seek to protect the intellectual property and proprietary technology production platform that we believe is important to our business, which includes seeking and maintaining patents covering our technology production platform and products, and any other inventions that are commercially or strategically important to the development of our business.

We also seek to protect the confidentiality of trade secrets that may be important to the development of our business.

Our ability to stop third parties from making, using, selling, offering to sell, or importing our products may depend on the extent to which we have rights under valid and enforceable patents or trade secrets that cover these activities.

In addition, our differentiated approach using polyclonal antibodies has no biosimilar pathway which provides a significant barrier to competitive polyclonal approaches.

For more information, please see “Risk Factors – Risks Related to Our Intellectual Property”.

The portfolio of intellectual property and trade secrets that we have developed includes patents related to the activity of our human artificial chromosome and methods that we expect to generate human IgGs at commercial scale.

The portfolio of intellectual property and trade secrets that we have developed includes patents related to the activity of our HAC and methods that we expect to generate hIgG at commercial scale.

The patent portfolio includes composition and method patents.

Our goal is to continue expansion of the breadth of claims and length of claim protections.

Our technologies may be difficult to replicate, creating potential barriers to entry, as our genetic engineering know-how and suite of proprietary production system IP and trade secrets have been developed and optimized over nearly two decades.

We expect our global patent protection to extend to 2041 and beyond with respect to producing commercial-scale hIgGs using our chromosome engineering that generates high concentrations of hIgGs in ungulates.

Our technologies may be difficult to replicate, creating potential barriers to entry, as our genetic engineering know-how and suite of proprietary production platform IP and trade secrets have been developed and optimized over nearly two decades.

We expect our global patent protection to extend to 2041 and beyond with respect to producing commercial-scale hIgG using our chromosome engineering that generates high concentrations of hIgG in ungulates.

However, we recognize that patents and other intellectual property rights in biotechnology are constantly evolving with many risks and uncertainties, which may affect those rights.

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These patent families cover:

• Granted patents in the U.S., Europe, Japan, and other major markets relating to a human artificial chromosome vector comprising a gene encoding the human antibody heavy chain, a gene encoding the human antibody light chain, and a gene encoding IgM heavy chain constant region derived (at least in part) from a nonhuman animal (expiring in 2033.

• Granted patents in the U.S., Europe, Japan, and other major markets relating to large-scale production of human IgGs by transgenic animals with high production of -human IgG of at least 1 g/L in sera (expiring in 2030 and in the U.S., 2031).

• Granted patents in the U.S., Europe, Japan, and other major markets relating to a HAC vector comprising a gene encoding the human antibody heavy chain, a gene encoding the human antibody light chain, and a gene encoding IgM heavy chain constant region derived (at least in part) from a nonhuman animal (expiring in 2033).

• Granted patents in the U.S., Europe, Japan, and other major markets relating to large-scale production of hIgG by transgenic animals with high production of hIgG of at least 1 g/L in sera (expiring in 2030 and in the U.S., 2031).

• A granted U.S.

patent and a pending U.S.

application relating to methods for producing human IgGs against a pathogen comprising injecting a non-human animal with a viral pathogen-derived DNA vaccine in at least two locations of the animal (expiring in 2036).

application relating to methods for producing hIgG against a pathogen comprising injecting a non-human animal with a viral pathogen-derived DNA vaccine in at least two locations of the animal (expiring in 2036).

• Granted U.S.

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• Pending U.S.

provisional application covering ungulate-derived human immunoglobulins that specifically bind influenza antigen, and methods of making and using the same in treating or preventing influenza (if issued, naturally expiring in 2042).

• Granted U.S.

that have a human chromosome fragment, and methods for making them (expiring in 2025).

These patents are not material to the Company at this time, and we believe patents issued subsequently allow the Company to maintain its competitive position.

provisional application covering ungulate-derived hIgG that specifically bind influenza antigen, and methods of making and using the same in treating or preventing influenza (if issued, naturally expiring in 2042).

• A granted U.S.

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These patents are not material to the Company at this time, and we believe patents issued subsequently allow the Company to maintain its competitive position.

PATENT SYSTEM

In most countries in which we file, including the United States, the patent term is 20 years from the earliest date of filing a non-provisional patent application.

In the United States, a patent’s term may potentially be lengthened by patent term adjustment, which compensates a patentee for administrative delays by the U.S.

PTO in examining and granting a patent considering delays on the part of the patentee or may be shortened if a patent is terminally disclaimed over an earlier filed patent.

• Granted U.S.

patent relating to methods of cloning a non-human mammal using transgenic ungulate embryos of one or more cells that have a human chromosome fragment and transgenic ungulate embryos of one or more cells that have a human chromosome fragment, and methods for making them (expired in March 2025).

These patents

are not material to the Company, and we believe patents issued subsequently allow the Company to maintain its competitive position.

US Patent System

In most countries in which we file patents, including the United States, the patent term is 20 years from the earliest date of filing a non-provisional patent application.

In the United States, a patent’s term may potentially be lengthened by patent term adjustment, which compensates a patentee for administrative delays by the United States Patent and Trademark Office (the “US PTO”) in examining and granting a patent considering delays on the part of the patentee or may be shortened if a patent is terminally disclaimed over an earlier filed patent.

In the United States, the patent term that covers an FDA-licensed biologic may also be eligible for patent term extension, which permits patent term restoration as compensation for the patent term lost during the FDA regulatory review process.

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For more information regarding the risks related to our intellectual property, see the section titled “Risk Factors – Risks Related to Our Intellectual Property”.

Patent Term Restoration

US Patent Term Restoration

Depending upon the timing, duration, and specifics of FDA approval of product candidates, some of a sponsor’s U.S.

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PTO, in consultation with the FDA, reviews and approves the application for any patent term extension or restoration.

Government Regulation

Government Regulations in the United States

In the United States, we expect our hIgG product candidates to be regulated by the FDA as biological products.

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Regulation of Transgenic Animals and New Animal Drugs

Department of Agriculture (USDA) regulates the company’s Tc Bovine husbandry activities, including housing, healthcare, and general management of these specialized animals.

Department of Agriculture (the “USDA”) regulates the company’s Tc Bovine husbandry activities, including housing, healthcare, and general management of these specialized animals.

This includes regulations and periodic facility inspections and reporting.

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The FDA considers, with limited exclusions, the altered genomic DNA in an animal to be a drug because such altered DNA is an article intended to affect the structure or function of the body of the animal, and, in some cases, intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in the animal.

In the United States, new animal drugs are subject to regulation under the Federal Food, Drug, and Cosmetic (the “FDCA”), and under the FDCA, in general, a new animal drug is “deemed unsafe” and adulterated unless the FDA has approved a new animal drug application (NADA) for its intended use or unless the drug is only for investigational use and conforms to specified exemptions for such use under an investigational new animal drug (INAD) exemption.

In the United States, new animal drugs are subject to regulation under the Federal Food, Drug, and Cosmetic (FDCA), and under the FDCA, in general, a new animal drug is “deemed unsafe” and adulterated unless the FDA has approved a NADA for its intended use or unless the drug is only

for investigational use and conforms to specified exemptions for such use under an investigational new animal drug (INAD) exemption.

Further, early in the development process, FDA has allowed the submission of information to FDA’s Center for Veterinary Medicine (CVM), without the establishment of an INAD file, such as through creation of a veterinary master file (VMF), subject to certain conditions such as restrictions on introducing any food derived from such investigational animals into the food supply.

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The FDA or the sponsor or its data safety monitoring board may suspend a clinical trial at any time on various grounds, including a finding that the research subjects or patients are being exposed to an unacceptable health risk.

Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being

conducted in accordance with the IRB’s requirements or if the biologic has been associated with unexpected serious harm to patients.

Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the biologic has been associated with unexpected serious harm to patients.

Concurrent with clinical trials, companies usually complete additional animal studies and must also develop additional information about the physical characteristics of the biologic as well as finalize a process for manufacturing the product in commercial quantities in accordance with GMP requirements.

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Furthermore, fast track designation, priority review, accelerated approval and breakthrough therapy designation do not change the standards for approval and may not ultimately expedite the development or approval process.

Emergency Use Authorizations

While, in most cases, a biologic must be approved by the FDA pursuant to a BLA before the product may be sold, when there is a public health emergency involving chemical, biological, radiological, or nuclear agents, including infectious diseases like COVID-19, new therapeutics may be distributed pursuant to an Emergency Use Authorization (EUA).

Under an EUA, the FDA may authorize the emergency use of an unapproved medical product or an unapproved use of an approved product for certain emergency circumstances to diagnose, treat, or prevent serious or life-threatening diseases or conditions when certain statutory criteria have been met, and after the Secretary of the Department of Health and Human Services has issued a declaration of emergency or threat justifying emergency use.

EUAs are intended to address serious or life-threatening diseases or conditions caused by a chemical, biological, radiological, or nuclear agent, including emerging infectious disease threats, such as the COVID-19 pandemic.

To receive an EUA, the product sponsor must demonstrate that the product “may be effective” in the prevention, diagnosis, or treatment of an applicable disease or condition.

Additionally, the FDA must determine that the product’s known and potential benefits outweigh the known and potential risks.

Further there must be no adequate, approved, and available alternative product for the indication.

Potential alternative products may be unavailable if there are insufficient supplies to meet the emergency need.

The FDA may establish additional conditions on an EUA that are necessary to protect public health, including conditions related to information that must be disseminated to health care providers and patients, the monitoring and reporting of adverse events, and record keeping.

Conditions may also relate to how a product is distributed and administered and how a product is advertised.

Importantly, EUAs are not full marketing approvals.

Rather, EUAs are only effective for the duration of the applicable EUA declaration.

Full approval of the product under applicable standards established under the FDCA would be necessary to continue to distribute the product absent an EUA.

EUAs may also be revised or revoked by FDA at any time.

Orphan Drug Designation

Under the Orphan Drug Act, the FDA may grant orphan designation to a drug or biologic intended to treat a rare disease or condition, which is a disease or condition that affects fewer than 200,000 individuals in the United States, or 200,000 or more individuals in the United States for which there is no reasonable expectation that the cost of developing and making available in the United States a drug or biologic for this type of disease or condition will be recovered from sales in the United States for that drug or biologic.

in the United States a drug or biologic for this type of disease or condition will be recovered from sales in the United States for that drug or biologic.

Orphan drug designation must be requested before submitting a BLA.

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The FDCA requires that a sponsor who is planning to submit a marketing application for a drug or biologic product that includes a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration submit an initial Pediatric Study Plan, or PSP, within sixty days of an end-of-Phase 2 meeting or as may be agreed between the sponsor and FDA.

The initial PSP must include an outline of the pediatric study or studies that the sponsor plans to conduct, including study objectives and design,

age groups, relevant endpoints and statistical approach, or a justification for not including such detailed information, and any request for a deferral of pediatric assessments or a full or partial waiver of the requirement to provide data from pediatric studies along with supporting information.

The initial PSP must include an outline of the pediatric study or studies that the sponsor plans to conduct, including study objectives and design, age groups, relevant endpoints and statistical approach, or a justification for not including such detailed information, and any request for a deferral of pediatric assessments or a full or partial waiver of the requirement to provide data from pediatric studies along with supporting information.

The FDA and the sponsor must reach agreement on the PSP.

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Department of Health and Human Services (“HHS”).

As previously mentioned, there is no biosimilar pathway for the complexity that exists in a polyclonal antibody drug product.

Additional Regulation

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We cannot predict, however, how changes in these laws may affect our future operations.

Regulation Outside of the United States

Government Regulation - Regulation Outside of the United States

In addition to regulations in the United States, we are, and will continue to be, subject to a variety of regulations in other jurisdictions governing, among other things, clinical studies and any commercial sales and distribution of our products.

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(formerly SAB Biotherapeutics, Inc.) was incorporated in April 2014 as a Delaware corporation (“Legacy SAB”).

We acquired all the intellectual property rights to Tc Bovine and the DiversitAb production system from Sanford Applied Biosciences, a wholly owned subsidiary of Sanford Health, to develop targeted human IgGs to specific targets and advance clinical development and commercialization.

The technology was originally contemplated in 1998 by professors at the University of Massachusetts Amherst and Amherst College who recognized a significant gap in immunotherapy applications, namely, using the way our bodies fight disease through a human immunoglobulin response.

We acquired all the intellectual property rights to Tc Bovine and the production platform from Sanford Applied Biosciences, a wholly owned subsidiary of Sanford Health, to develop targeted hIgG to specific targets and advance clinical development and commercialization.

The technology founders established a biotech company called “Hematech” to develop the technology.

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On December 31, 2012, KHK divested the technology and transferred ownership of all property, assets, and intellectual property of Hematech to Sanford Health and the technology was further developed by Sanford Applied Biosciences until we acquired it in its entirety in June 2014.

Since acquiring the technology in 2014, we have continued to develop intellectual property and specifically targeted human IgGs to multiple disease indications, and we have conducted or collaborated in eight clinical trials (six of which are in review), where we have demonstrated safety and efficacy in multiple Tc Bovine-derived human IgG product candidates.

Since acquiring the technology in 2014, we have continued to develop intellectual property and specifically targeted hIgG to multiple disease indications, and we have conducted or collaborated in eight clinical trials (six of which are in review), where we have demonstrated safety and efficacy in multiple Tc Bovine-derived hIgG product candidates.

We have developed our rapid response capabilities and completed proof of concept using private resources as well as over $200 million of funds awarded from the U.S.

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and Legacy SAB became a wholly-owned subsidiary of SAB Biotherapeutics, Inc.

Corporate Information

Our principal executive offices are located at 2100 East 54th Street North, Sioux Falls, South Dakota 57104, and our telephone number is (605)-679-6980.

In June 2024, we announced a new brand, logo mark and visual identity to reflect the company’s strategic evolution in immunotherapy as SAB BIO.

Available Information

Our principal executive offices are located at 777 W 41st St.

Suite 401 Miami Beach, FL 33140, and our telephone number is (605)-679-6980.

Our corporate website address is www.sab.bio.

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The public may read and copy any materials that we file with the SEC electronically through the SEC website (www.sec.gov).

The information contained on the SEC’s website is not incorporated by reference into this Annual Report on Form 10-K and should not be considered to be part thereof.

The information contained on the SEC’s website is not incorporated by reference into this Annual Report and should not be considered to be part thereof.

Human Capital

As of December 31, 2023, we had 57 full-time employees, including 8 who hold advanced degrees.

Of these employees, 35 were engaged in research and development activities, 7 were engaged in clinical activities and 14 were engaged in general and administrative activities.

As of December 31, 2024, we had 63 full-time employees, and of these employees, 37 were engaged in research and development activities, 9 were engaged in clinical activities and 17 were engaged in general and administrative activities.

As of December 31, 2024, none of our employees were represented by labor unions or covered by collective bargaining agreements.

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We emphasize several measures and objectives in managing its human capital assets, including, among others, (i) employee safety and wellness, (ii) talent acquisition and retention, (iii) employee engagement, development, and training, (iv) diversity and inclusion and (v) compensation.

These targeted ideals may include annual bonuses, stock-based compensation awards, a 401(k) plan with employee matching opportunities, healthcare, and insurance benefits, health savings and flexible spending accounts, paid time off, family leave, family care resources, and/or employee assistance programs.

targeted ideals may include annual bonuses, stock-based compensation awards, a 401(k) plan with employee matching opportunities, healthcare, and insurance benefits, health savings and flexible spending accounts, paid time off, family leave, family care resources, and/or employee assistance programs.

We also provide our employees with access to various innovative, flexible, and convenient health and wellness programs.

1 unchanged sentence

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business