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Item 1. Business

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We are a clinical-stage biopharmaceutical company focused on the development of powerful and proprietary immunotherapeutic polyclonal human antibodies to treat and prevent infectious diseases and immune an autoimmune disorders, including infectious diseases resulting from outbreaks and pandemics such as the COVID-19 pandemic and respiratory diseases that have a more significant impact on the immune compromised population.

Using private resources and more than $200 million of funds awarded from the U.S.

Government emerging disease and medical countermeasures programs since September 2019, we have developed a novel drug development platform, that we refer to as our DiversitAb platform.

This platform is based on the power of the human immune system and has the unique capability to generate large quantities of specifically targeted, high-potency, fully-human natural polyclonal antibodies without the need for convalescent plasma or human donors.

Over a span of two decades, our founding scientists have refined, optimized, and advanced genetic engineering and antibody science to develop transchromosomic cattle (which we refer to as Tc Bovine) that produce fully-human antibodies.

These Tc Bovine form a key component of our versatile DiversitAb platform.

We are leveraging our DiversitAb platform to discover and develop product candidates with the potential to be first-in-class against novel targets or best-in-class against known, complex targets that treat diseases with significant unmet medical needs, including infectious and respiratory diseases, immune and autoimmune disorders, and oncology.

We are a clinical-stage biopharmaceutical company focused on the development of proprietary immunotherapeutic fully-human antibodies, or fully-human immunoglobulins (hIgGs), to treat and prevent immune and autoimmune disorders as well as infectious diseases that have significant mortality and health impacts on high-risk patients.

These antibodies are target-specific and polyclonal, meaning they are made up of many different hIgGs that bind to multiple sites specific to an immunogen as opposed to a monoclonal antibody that binds to only a single site.

Our development programs include autoimmune disorders, gastroenterological, and respiratory diseases.

Using private resources and more than $200 million of funds awarded by the U.S.

Government emerging infectious disease and medical countermeasures programs since September 2019, we have developed a novel drug development platform, which we refer to as our DiversitAb platform.

This platform is based on the natural human immune system and has the unique capability to generate large quantities of specifically targeted, high-potency, hIgG that target multiple epitopes, antigens or binding sites without the need for producing these antibodies from convalescent plasma or human donors.

We have refined, optimized, and advanced genetic engineering and antibody science to develop transchromosomic cattle (which we refer to as Tc Bovine) that produce hIgGs and the engineering of the platform drives IgG1 production primarily.

These Tc Bovine form a key component of our versatile DiversitAb platform, a fully scalable production system for producing immunotherapies to multiple disease indications.

Our platform represents the technology that can produce disease-targeted, fully human IgG without the need for human donors.

We are leveraging our DiversitAb platform to discover and develop product candidates with the potential to be first-in-class against novel targets or best-in-class against known, complex targets that treat diseases with significant unmet medical needs, including immune and autoimmune disorders, infectious gastroenterological and respiratory diseases, and oncology.

Key Product Differentiators Over Existing Technologies

The DiversitAb platform represents the first of its kind technology to produce large scale human high-titer, high-avidity antibodies across multiple modalities and a new source for novel treatments from a unique targeted human hIgG discovery and product development engine.

(See Figure 1).

Polyclonal Antibody Development (hIgG)  represents the first time that fully human antibodies allow targeting to complex diseases with multiple dysregulated pathways through hyperimmunization to be fully explored as potent immunotherapies that can target multiple different targets and different modes of action all in the same regulated product.

This is the first scalable technology that mimics the natural way humans fight disease through production of hIgG.

Human Immunoglobulin (hIgG)  is used to treat patients with primary and secondary immune deficiencies as well as other indications and SAB’s antibodies have demonstrated comparability to approved subcutaneous delivered, human-derived products with the potential benefits that come from having a controlled source of human antibodies without the need for human donors.

Monoclonal Antibody (mAb) Discovery  is accomplished in two ways using the DiversitAb platform:

1) by sequencing antibodies produced from Tc Bovine B-cell clones;

and 2) by direct sequencing of target-specific immunogen purified hIgG produced at high concentrations, each representing the potential to capture unique monoclonal antibody candidates.

Versatile Antibody Platform with Ability to Capture Multiple Modalities

While we can rapidly generate specific, high-affinity monoclonal antibodies, the biggest potential in delivering new highly effective treatments lies within the multi-target approach.

Complex diseases are conditions where multiple targets and multiple dysregulated pathways are involved.

Except for diseases driven by a single genetic mutation, a vast majority of diseases that consistently cause human suffering with high unmet medical needs are complex.

Examples of complex diseases include autoimmune disorders such as Type 1 diabetes or cancer.

Historically we treat complex diseases by prescribing multiple single-target treatments to patients, that can have drug interactions and toxicities, and from the R&D perspective, inevitably results in operational, organizational, and financial challenges tied to requirements to conduct very large, long, and costly combination trials.

Our DiversitAb platform develops treatments that address multiple dysregulated pathways, multiple targets, multiple epitopes in a single powerful fully human immunoglobulin treatment.

Regulation of this approach primarily rests within the U.S.

FDA Center for Biologics Evaluation and Research (CBER), which regulates the safety, activity and potency of the immunoglobulin mixture and not by characterization of individual antibody molecules.

hIgGs have natural multivalency that can be effective against highly mutating viruses and other diseases with epitope mutations or variants, due to the large number of different hIgGs and their ability to bind to or block multiple epitopes.

hIgGs are the natural way the human body fights disease, as they work organically with the rest of the immune system to activate effector cell function, which are the cells that defend the body in an immune response.

hIgGs can be rapidly and consistently produced to target many different diseases, and the regulatory pathway for plasma-derived hIgGs allows for broad potency to multiple disease targets within a single drug product vial.

Our hIgGs can be used as both pre- and post-exposure prophylaxis and treatments.

Our discovery and hIgG production process can occur simultaneously using our DiversitAb platform, which accelerates development of our hIgGs by leveraging the natural antibody selection that occurs in our Tc Bovine.

We have a demonstrated regulatory pathway through the Center for Biologics Evaluation and Research (CBER) that understands our science and is familiar with the multivalent and multitarget properties of our single vial drug products.

This further streamlines our ability to rapidly and efficiently develop new and novel drug products where mAbs simply can’t replicate or duplicate our drug product attributes.

DiversitAb Platform Produces a Natural Mixture of Many Human hIgGs

that bind to Multiple Epitopes but are Regulated as a Single Product

Recent Milestones

Since September 2019, we achieved multiple milestones, including:

Established proof-of-concept for our DiversitAb platform.

Fully enrolled Phase 2a challenge study for SAB-176 in adults infected with influenza virus.

Advanced to Phase 3 of NIH-Sponsored ACTIV-2 Trial based upon DSMB at interim analysis for SAB-185 (COVID-19) and reached 50% enrollment.

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

Performed multiple clinical trials establishing the safety profile of hpAbs produced in DiversitAb platform in hundreds of patients and have demonstrated proof of clinical concept for our DiversitAb platform across three SAB-sponsored INDs and one CTA (filed Ex-US) that encompass seven clinical trials from Phase 1 to Phase 3 across treatment of three indications (MERS, Influenza, and COVID-19) briefly summarized below (Figure 3)

Completed Phase 2a challenge study for SAB-176 in adults infected with influenza virus and Phase 2 study for SAB-185 in adults infected with SARS-CoV-2 virus.

Announced topline data demonstrating SAB-176 met its primary endpoint in our Phase 2a challenge study in adults infected with influenza virus.

Announced that recent data demonstrated that SAB-185 retains neutralization activity against the Omicron SARS-CoV-2 in an in vitro pseudovirus model.

Reported positive topline Phase 2 virology data demonstrating SAB-185 met Criteria for advancement to Phase 3.

Proprietary DiversitAb Platform

Our proprietary DiversitAb platform gives us the unique ability to generate targeted, fully-human, polyclonal antibodies without the need for human donors or serum.

These diverse and high potency antibodies can be targeted to viruses, bacteria, toxins, and human immunogen targets.

The current platform relies on advanced genetic engineering that functionally replaces bovine antibodies with human antibodies (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.

The human antibody genes have been further engineered to efficiently produce a diverse repertoire of human immunoglobulin G (which is referred to as IgG) 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 with high concentrations of antibodies and respond effectively to immunogen challenge by producing high potency, high avidity polyclonal antibodies.

The novel capability of the DiversitAb platform in harnessing the natural human biological immune response makes our platform well-suited to address multiple therapeutic categories, presenting potential opportunities for new therapies to address unmet medical needs.

The following graphic depicts the main elements of product development and manufacturing using our DiversitAb platform:

Through our DiversitAb platform, we have engineered a systematic therapeutic engine that emulates the way that nature synergistically targets the complexity of human disease.

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

Develop Immunogen for Disease Target .

An immunogen is developed for a specific target.

The platform is designed to address virtually any target including bacteria (whole killed), viruses, toxins, plasmid DNA, cells, and human tissues.

Hyperimmunize Tc Bovine .

Tc Bovine are genetically engineered to produce fully-human antibodies, and then hyperimmunized with the immunogen, driving the immune response beyond protective levels.

Collect Plasma .

The target specific human antibodies are collected from the Tc Bovine as plasma donations.

Isolate Human Antibodies .

Human antibodies are then isolated from the plasma through a plasma fractionation process and tested per established protocols.

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

Our DiversitAb platform is replicable and scalable.

We believe that targeted human antibodies can be produced to counteract the same immunogen or multiple immunogens in as many Tc Bovine as necessary to generate sufficient doses of any target product.

We can scale manufacturing by adding more Tc Bovine that are hyperimmunized to produce more plasma.

Downstream processing primarily involves plasma fractionation to purify human IgG from all other plasma proteins to meet product specifications.

Consistency of product is achieved by testing the potency of antibodies 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 platform to develop countermeasures for emerging diseases and pandemics represents a significant advantage relative to other antibody manufacturers.

We have successfully utilized our DiversitAb platform technology to generate early proof-of-concept and initial clinical lots that address specified immunotherapy targets in as little as 90 days, including completion of IND-enabling studies, in response to the emerging COVID-19 pandemic.

We have vertically integrated the platform technology across a significant series of value inflection points.

Our capabilities include advanced animal reproduction methods (cloning) to produce Tc Bovine, animal husbandry, immunogen development, plasma collection, plasma purification, drug substance manufacturing and product fill/finish, nonclinical and clinical study management, quality assurance, quality control, regulatory compliance, and program collaboration.

We have built a broad-based network of third-party collaborators, service providers, vendors, consultants, and government partners that can help support each of these vertically integrated activities.

Three-Pronged Business Strategy

Our strategy for product development relies on three distinct approaches which utilize our DiversitAb platform to develop product candidates:

Government Funded Programs

Partner Collaborations

Proprietary Pipeline Programs

Government Funded Programs

We are leveraging our relationships with various government agencies to advance programs using our DiversitAb platform.

Our government funded programs have resulted in the advancement of our Rapid Response Antibody Program as well as the rapid advancement of our SAB-185 program from preclinical through our participation in the Phase 3 arm of the ACTIV-2 master protocol.

Rapid Response Antibody Program

Since our founding in 2014, we have employed our DiversitAb platform to complete pre-clinical development of a dozen new products under a rapid timeline.

Through commercial and government collaborations, we have produced new products from target identification through completion of IND-enabling studies in as little as 90 days.

This timeline includes product concept, identifying and producing an immunogen, hyperimmunization of Tc Bovine, collection of plasma, purification of antibodies and initial potency assays to qualify the product candidate.

We continue to innovate and vertically integrate workstreams to discover and develop products.

Through a replicable combination of complex proprietary engineering and industry standard purification processes, we have demonstrated the ability to produce effective, high potency human polyclonal antibodies for a variety of targets.

In response to the COVID-19 pandemic and the need for an effective therapeutic, we were able to advance SAB-185 from immunogen to the clinic in 128 days.

Our current agreement with Joint Program Executive Office-Enabling Biotechnologies (JPEO-EB) within the Department of Defense (DOD) was specifically directed to rapidly develop a medical countermeasure to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the result of which became SAB-185.

The initial agreement was designed as a staged escalation of our Rapid Response Antibody Program to known and unknown targets.

This initial scope, including additional funding support through the Defense Health Authority (DHA) and Biomedical Advancement Research and Development Authority (BARDA), and inclusion in the Countermeasures Acceleration Group (formerly Operation Warp Speed), was expanded to include SARS-CoV-2.

As a result of our COVID-19 pandemic response, we successfully demonstrated our Rapid Response Antibody Program.

The work we have completed to date has also resulted in significant increases in production capacity and accelerated advancement of our capability to provide a readiness system at scale.

We continue work on the Rapid Response Antibody Program and completing the framework for a vertically integrated product development system that manages products from discovery through licensure and commercial manufacturing on an accelerated timeline.

SAB-185 (anti-SARS-CoV-2 ) Program (COVID-19)

SAB-185 is a fully-human, specifically targeted, highly potent, and broadly neutralizing human polyclonal antibody therapeutic candidate for COVID-19.

SAB-185, generated from the full-length spike protein of the SARS-CoV-2 Wuhan strain, has shown neutralization of the Munich, Washington, South African, Delta, Lambda, and other variant strains in preclinical and nonclinical studies.

In addition, recent data has demonstrated that SAB-185 retains neutralization activity against the Omicron SARS-CoV-2 in an in vitro pseudovirus model.

Preclinical data has shown SAB-185 to be significantly more potent than human-derived COVID-19 convalescent IgG.

We have completed multiple clinical and nonclinical studies to date, including a Phase 1 trial in healthy volunteers, and a Phase1b and Phase 2 clinical trial, both in COVID-19 patients.

SAB-185 was being assessed in Phase 3 clinical trial as part of the ACTIV-2 master protocol, sponsored, funded and conducted by the National Institute of Allergy and Infectious Diseases, part of the U.S.

National Institutes of Health (the NIH) in collaboration with the AIDS Clinical Trials Group (ACTG).

On February 28, 2022, the NIH decided to discontinue the ACTIV-2 program after determining that the decrease in hospitalizations resulted in operational futility and made it impossible to demonstrate statistically significant clinical efficacy with the existing study design.

We have advanced SAB-185 in collaboration with the U.S.

Government, as part of the Countermeasures Acceleration Group, formerly Operation Warp Speed.

We filed the IND application, produced the initial clinical doses and entered the Phase 1 clinical trial in just 128 days from the program initiation.

SAB-185 was designed and developed without the need for human convalescent plasma or human B-cell donations.

We continue to work with multiple U.S government collaborators to evaluate a number of options for the continued evaluation and testing of SAB-185, including advanced clinical development, targeting specialized populations, such as immune compromised, and alternate routes of administration.

In addition, we intend to use the data from the Phase 3 portion of the ACTIV-2 program to help focus the continuing SAB-185 program.

We expect the full data readout for the Phase 2 NIH ACTIV-2 trial to be available Mid-2022.

Partner Collaborations

We are pursuing a number of potential partner collaborations and license agreements for the development of product candidates with the potential to create first-in-class or best-in-class treatments.

We expect that our partner collaborations will service two distinct channels:

our discovery program to identify targets which can be commercialized solely by our partners and through joint development collaborations which leverage our technology and a potential partner’s resources to rapidly co-develop therapies based on novel targets developed using our DiversitAb platform.

Advantages of Polyclonal Antibodies

While we can produce monoclonal antibodies when desirable, we believe that our human polyclonal antibodies have several advantages over certain monoclonal antibodies.

Polyclonal antibodies can be rapidly and consistently produced to target many different diseases and the regulatory pathway for plasma-derived polyclonals allows for broad potency to multiple disease targets within a single drug product.

Because polyclonal antibodies are the natural way our bodies fight disease, they work organically with the rest of the immune system to activate effector cell function, which are the cells that defend the body in an immune response.

Polyclonal antibodies can be used as both pre- and post-exposure prophylaxis and treatments and can be effective against highly-mutating viruses and other diseases with epitope mutations or variants as a result of the large number of different antibodies and their ability to bind to or block multiple epitopes.

A study was conducted in 2014 to demonstrate how Tc Bovine derived human polyclonal antibodies interacted with cellular immunity as compared with monoclonal antibodies.

The data shown below demonstrated the ability of an anti-Ebola Tc Bovine-produced human polyclonal antibody product candidate to activate viable human effector cells as compared to monoclonal antibodies and negative controls.

In this study, micro-beads coated with Ebola glycoprotein were cultured with human monocytes, neutrophils, and Natural Killer cells in the presence of test agents.

In the graphic above, the lines with solid black and white circles represent monocyte and neutrophil phagocytosis in Figure A and B and Natural Killer cell degranulation in Figure C from the serum of two Tc Bovines hyperimmunized with Ebola glycoprotein on eight occasions.

The blue and purple bars represent two Tc Bovine human polyclonal antibody lots produced from their plasma after the third and fourth immunizations and from the sixth, seventh and eighth immunizations respectively.

The red and white bars represent a naïve Tc Bovine human polyclonal antibody and normal saline respectively.

The green and orange bars represent two anti-Ebola glycoprotein monoclonals.

As can be seen, both lots of anti-Ebola Tc Bovine human polyclonal antibodies demonstrated the ability to induce monocyte and neutrophil cell phagocytosis and Natural Killer cell degranulation.

The lot produced from plasma after the sixth to the eighth immunization had better activity and is consistent with avidity maturation of the polyclonal antibodies.

In contrast, while the monoclonals induced monocyte phagocytosis, only one was able to induce neutrophil phagocytosis.

And critically, neither monoclonal antibody had the ability to induce Natural Killer cell degranulation.

This indicates that Tc Bovine-produced human polyclonal antibodies induce human effector cells which are critically important to the control of viruses, bacteria, and other pathogens.

Advantages of our Polyclonal Antibody Approach

Our novel multivalent polyclonal approach, including hyperimmunization of the Tc Bovine results in specifically targeted, highly potent, high avidity, broadly diverse, fully human polyclonal antibodies, overcoming the challenges and exceeding the capabilities of traditional animal and human-derived polyclonal antibodies.

Animal-derived polyclonal antibodies, such as from horses or rabbits, have the disadvantage of being immunogenic in humans and they often cause severe hypersensitivity reactions limiting their clinical use or reuse as animal antibodies.

Human-derived polyclonal antibodies are limited by the difficulty of collecting from humans and the inability of humans to produce antibodies to endogenous proteins under normal circumstances.

Therefore, there is a significant potential advantage of Tc Bovine-produced human polyclonals in their ability to bind to both foreign exogenous or human endogenous protein targets, activate human effector cells, and not cause hypersensitivity reactions.

Initial Preclinical Studies and Variant Resistance

This table provides an overview of our in vivo animal data from 2008 to 2018 that has enabled several pre-clinical studies with efficacy data demonstrating the broad potential of the DiversitAb platform to address diverse human diseases, globally.

As shown in the table, infectious disease has been a strategic proving ground for the validation of our platform.

Listed above are several significant human diseases for which adequate countermeasures may not exist.

These include Ebola, Middle East respiratory syndrome coronavirus (MERS-CoV), and Zika, among others.

We have completed preclinical development for multiple potential infectious disease products to address these global emerging human biothreats, and we have repeatedly demonstrated 100% preclinical efficacy in several animal models for most targets.

This consistent in vivo efficacy demonstrates the broad potential of the platform and has ultimately led to the clinical advancement of multiple Phase 1 clinical trials including MERS-CoV, and our advanced infectious disease pipeline products, SAB-176 and SAB-185.

We have also demonstrated preclinical efficacy as both a prophylactic and therapeutic treatment.

In a study conducted in 2017, we produced a fully-human polyclonal antibody, SAB-131, against Venezuelan Equine Encephalitis Virus (VEE).

VEE is both a potential pandemic and biothreat pathogen for which we believe counter measures to be seriously lacking.

Three cohorts of mice were challenged with a lethal dose of VEE.

In contrast to the control group (black lines) all mice treated prophylactically or therapeutically with SAB-131 survived with no to minimal weight loss, indicative of minimal clinical symptoms.

Additionally, images of the brain of each cohort demonstrate that SAB-131 can prevent or reduce viral encephalitis, which is a natural progression of the disease for this pathogen.

This is visible by the reduction of signal intensity or viral load in the brain between the control group and the prophylactic and therapeutic treated groups.

This suggests that these antibodies can protect against neurological pathogens and potentially address unmet neurological diseases in humans.

Another potential therapeutic advantage of our polyclonal antibodies is their ability to effectively neutralize highly mutating pathogens such as Hantaan viruses.

A study conducted in 2019 demonstrated SAB-159, an anti-Hantaan polyclonal antibody, completely neutralized the original wild-type virus, as well as both single mutants, and a double mutant of Hantaan virus.

Effective neutralizing potency is indicated by the low in vitro IC50 threshold concentration below 100ng/mL indicated by the small grey area at the bottom of the graph.

In contrast, two neutralizing monoclonal antibodies alone or in combination could not completely neutralize the three different mutant strains.

Initial Preclinical Toxicology (SAB-301 Anti-Middle East Respiratory Syndrome Coronavirus)

We tested proprietary Tc Bovine-derived human polyclonal antibodies (SAB-301 Anti-MERS-CoV) to confirm that they were safe and tolerable in a preclinical toxicology study conducted in 2016.

The objectives of this study were to (i) determine potential toxic effects and target organs of toxicity, (ii) identify a no observed adverse effect level (NOAEL) and the maximum tolerated dose (MTD) of SAB-301 in New Zealand White male and female rabbits after a single intravenous dose administration and (iii) determine the toxicokinetic parameters and immunogenicity after single dose administrations.

We may use information from this study to design subsequent toxicity studies and to determine the suitability of the proposed human dose.

In this study, male and female New Zealand White rabbits were given a single intravenous infusion of SAB-301 over 30 minutes at 50 mg/kg (600 mg/m2, Group 2) or at 370 mg/kg (4440 mg/m2, Group 3) on Day 1.

The concentration of the dose formulation was constant (37.29 mg/ml) while dose volume varied for the treated groups.

A control group was given vehicle (10 mM glutamic acid monosodium salt, 262 mM D-sorbitol, 0.05 mg/ml Tween 80, pH 5.5) at a volume (9.9 ml/kg) equivalent to that of the high dose group.

The following parameters were evaluated:

mortality/morbidity, clinical observations, body weights, food consumption, ophthalmology, clinical pathology (hematology, serum chemistry and coagulation), urinalysis, gross necropsy, histopathology, toxicokinetic analysis and immunogenicity.

All animals survived and no drug-related effects were observed for clinical observations, ophthalmology, food consumption, body weight, hematology and coagulation parameters, gross necropsy findings or histopathology.

Increases of 2- and 3.9-fold in globulin (GLO) were observed in males treated with SAB-301 at 50 and 370 mg/kg, respectively, compared with the controls on Day 3.

GLO levels were also increased, 1.4- and 4.4-fold, respectively in the females in the 50 and 370 mg/kg groups, compared with the controls.

Correlatively, the albumin to GLO ratio (ALB/GLO) was decreased, while total protein (TPR) was increased in these animals.

By Day 50, the GLO, ALB/GLO ratio and TPR returned to normal.

These changes are simply an increase in total globulin due to the intravenous injection of SAB-301, a human polyclonal antibody, into the blood stream.

The analytical assays used to measure total globulin and protein in clinical chemistry cannot distinguish between endogenous protein and injected antibodies.

In fact, bioanalysis showed that there were significant amounts of SAB-301 in serum on Day 4 in a dose-dependent manner.

Therefore, this response is not considered an adverse effect of SAB-301, but is simply the increased presence of globulin in the blood stream after the administration of the test article.

Toxicokinetic analysis was performed on the measurable serum concentrations of SAB-301 in male and female rabbits after an intravenous infusion at dose levels of 50 and 370 mg/kg.

There were non-linear increments in Cmax and AUCinf with a dose increase from 50 to 370 mg/kg.

Mean apparent V values (33.4 to 80.6 ml/kg) indicate distribution of SAB-301 primarily in the vascular compartment.

Females had a 60% greater exposure of SAB-301 at the higher dose (370 mg/kg), possibly due to a slower clearance rate in this group and formation of antibodies to SAB-301 in males.

In conclusion, a single intravenous infusion of SAB-301 over 30 minutes to male and female New Zealand White rabbits did not produce overt adverse effects and did not have any target organs of toxicity.

Therefore, the maximum tolerated dose (MTD) of SAB-301 was not determined but we believe it to be greater than 370 mg/kg (4440 mg/m2) for a single intravenous dose administration in rabbits.

The NOAEL of SAB-301 is considered to be at least 370 mg/kg (4440 mg/m2) for a single intravenous dose administration in rabbits.

First-in-Man Clinical Safety and Efficacy

The first-in-man clinical trial of SAB-301for MERS-CoV, conducted in 2017 and sponsored by the NIH, evaluated safety of this Tc Bovine-derived human polyclonal.

The study was a blinded, placebo controlled, ascending dose study in healthy adults that investigated doses of 1.5 mg/kg to 50 mg/kg of intravenously administered product in 38 participants that were followed for 90 days post-infusion.

The conclusion was that SAB-301 was safe and well tolerated.

Pharmacokinetic analysis demonstrated a half-life of the anti-MERS-CoV human polyclonal antibodies of 28 1/2 days, which is the reported half-life of human-derived IgG antibodies in humans.

Importantly, anti-drug antibodies, or antibodies to ligands used in our DiversitAb purification process, or anti-bovine plasma protein antibodies were not detected.

Another clinical study conducted in 2017 at Brigham and Women’s Hospital, showed an initial indication of efficacy in Tc Bovine-derived anti-Mycoplasma human polyclonal antibodies in an immunosuppressed 68-year-old man diagnosed with a M.

hominis septic polyarthritis who developed a chronically draining right hip fistula following a failed hip replacement surgery.

The fistula is shown on the lower left above.

He was treated with human-derived intravenous immunoglobulin and antibiotics for seven years during which time the mycoplasma became multi-antibiotic resistant.

At the request of the patient and his physician, we produced the anti-mycoplasma human polyclonal therapeutic which was intravenously administered to the subject at doses up to 100 mg/kg as shown in the center table above.

This was done under an FDA allowed Phase 1b study.

The human polyclonal antibody product was well tolerated, and the subject’s mycoplasma load fell to undetectable levels with rapid healing and closure of the fistula as shown on the lower right.

The patient then elected to undergo a repeat hip replacement surgery and he developed a Staphylococcus Aureus and other bacteria wound infection including mycoplasma.

The patient was then re-treated with the Tc Bovine-derived human polyclonal antibodies which resulted in marked reductions in mycoplasma load as shown in the center table.

This remarkable case study demonstrates the potential utility of Tc Bovine-derived human polyclonal antibodies to treat serious antibiotic resistant infections in general, but also the potential opportunity to produce specific human polyclonal antibody therapeutics to treat individuals with intractable infections using a personalized medicine approach.

Reported positive topline Phase 2 virology data demonstrating SAB-185 met criteria for advancement to Phase 3 and completed 50% enrollment in Phase 3.

Phase 3 patient safety follow-up is ongoing.

Announced that recent data demonstrated that SAB-185 retains neutralization activity against the Omicron SARS-CoV-2 in an in vitro  pseudovirus model and in a human ACE2 receptor in vivo  model study.

Completed IND enabling in-vivo pilot and GLP tox safety and pharmacodynamic studies for SAB-142 for autoimmune disorders including Type 1 Diabetes.

Established proof-of-concept for production of human anti-idiotype IgGs to human auto-antibodies using the DiversitAb platform.

DiversitAb ™

Platform Clinical Validations

Accomplishment Summary

Fact Sheet of Accomplishments

Figure 4 shows a summary of our accomplishments in proof of principle and proof of concept for the use of the DiversitAb platform in development of multiple assets as well as the establishment of a clear regulatory framework.

Two (2) or less is the number of years it takes us to develop a new investigational product from concept to IND filing.

Rapid response during the Covid-19 pandemic allowed for IND enablement and the start of Phase 1 clinical trials in 128 days.

Eleven (11) is the number anti-infectives assets that have been developed in the DiversitAb platform through proof of concept and beyond in the preclinical or clinical setting.

Ninety (90) is the percent of our biologic immunotherapeutics that successfully reached predefined milestones.

Greater than seven hundred (>700) subjects have been treated with investigational therapeutics produced by the DiversitAb platform.

Zero (0) assets to date lost total efficacy to viral escape mutants.

One (1) SAB Biotherapeutics is the First and Only company able to produce an unlimited supply of fully human broadly neutralizing hIgGs without the need for human donors.

Pipeline Programs

We are leveraging our DiversitAb platform to advance a robust pipeline of differentiated antibody-based therapies for the treatment of infectious diseases and immune system disorders.

We are focused on developing, with partners or on our own, product candidates where we believe a differentiated human polyclonal approach has the greatest potential to be either first-in-class against novel targets or best-in-class against known, but complex, targets to treat diseases with significant unmet medical needs, including infectious diseases such as COVID-19 and influenza, immune system disorders, including T1D, organ transplantation and early discovery oncology.

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

We are focused on developing, with partners or on our own, product candidates where we believe a differentiated human hIgG 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 diseases such as influenza, CDI, immune system disorders (including Type 1 diabetes or T1D), organ transplantation and early discovery oncology.

We believe route of administration is also an important component of the ability to access specific markets.

While we are currently testing our lead programs using intravenous administration, we are pursuing the development of alternate routes of administration as an expansion of our market reach.

These include intramuscular and other administration methods.

The following summarizes the status of the therapeutic candidates in our current pipeline:

SAB-185 (anti-SARS-CoV-2)

SAB-185 is a fully-human, specifically targeted, highly potent, and broadly neutralizing human polyclonal antibody therapeutic candidate for COVID-19.

These include subcutaneous and intramuscular routes of administration.

Figure 5 summarizes the status of the therapeutic candidates in our current pipeline.

Summary of Therapeutic Candidates in Our Current Pipeline

Potential applications of multi-target multi-epitope approach are virtually limitless and our pipeline shows examples of targeted hIgG assets across several therapeutic areas.

We continue building on our successful track record in respiratory diseases, including previous positive clinical trials in COVID-19 and Middle Eastern Respiratory Syndrome (MERS) indications, by focusing on SAB-176, a multitarget hIgG broadly neutralizing anti-influenza immunotherapy.

This is one of the most advanced clinical assets and has progressed to mid-Phase 2 stage. 

Another asset is SAB-195, the first human hIgG for treatment of Clostridioides difficile Infection (also known as CDI or C.

diff infection) and for prevention of recurrence of CDI. This asset is preclinical stage and anticipated to proceed to IND in the next 12 months.

Finally, we are entering into the autoimmunity space with SAB-142, another preclinical stage asset, that is a disease-modifying fully human hIgG aimed to prevent onset or disease progression of Type 1 Diabetes and subsequently expand into other immunology indications.  Additionally, we have a robust discovery and preclinical-stage pipeline in anti-idiotype disorders as well as emerging oncology programs.

Our top portfolio is balanced across early and late development assets with meaningful inflection points delivered every 12 months to assure rapid de-risking of individual assets and investments into these three programs as well as the entire DiversitAb platform. (See Figure 6).

Clinical Development Programs and Expected Asset Progress

HIGH RISK COVID-19

SAB-185 (anti-SARS-CoV-2) Demonstrates Clinical Advancement to Phase 3 Clinical Trials

SAB-185 is a fully-human, specifically targeted, highly potent, and broadly neutralizing human IgG therapeutic candidate for COVID-19.

In addition, recent data has demonstrated that SAB-185 retains neutralization activity against the Omicron SARS-CoV-2 in an in vitro pseudovirus model.

Preclinical data has shown SAB-185 to be significantly more potent than human-derived COVID-19 convalescent IgG.

We have completed multiple clinical and nonclinical studies to date, including a Phase 1 trial in healthy volunteers, and a Phase1b and Phase 2 clinical trial, both in COVID-19 patients.

National Institutes of Health (the NIH) in collaboration with the AIDS Clinical Trials Group (ACTG).

On February 28, 2022, the NIH decided to terminate the ACTIV-2 program after determining that the decrease in hospitalizations resulted in operational futility and made it impossible to demonstrate statistically significant clinical efficacy with the existing study design.

We have advanced SAB-185 in collaboration with the U.S.

In addition, recent data has demonstrated that SAB-185 retains neutralization activity against the Omicron variant of COVID-19 in an in vitro pseudovirus model.

Preclinical data has shown SAB-185 to be significantly more potent than human-derived COVID-19 convalescent hIgG.

We have completed multiple clinical and nonclinical studies to date, including a Phase 1 trial in healthy volunteers, and a Phase1b and Phase 2b clinical trial, both in COVID-19 patients.

SAB-185 was being assessed in a Phase 3 clinical trial as part of the ACTIV-2 master protocol, sponsored, funded and conducted by the National Institute of Allergy and Infectious Diseases, part of the U.S.

National Institutes of Health (NIH) in collaboration with the AIDS Clinical Trials Group (ACTG).

On February 28, 2022, the NIH decided to terminate the ACTIV-2 program, including ALL other COVID-19 products active at the time in the ACTIV-2 protocol, after determining that the decrease in hospitalizations resulted in operational futility and made it cost-prohibitive to demonstrate statistically significant clinical efficacy with the existing study design.

SAB-185 was advanced in collaboration with the U.S.

Government, as part of the Countermeasures Acceleration Group, formerly Operation Warp Speed.

We filed the IND application, produced the initial clinical doses, and entered the Phase 1 clinical trial in just 128 days from the program initiation.

SAB-185 was designed and developed without the need for human convalescent plasma or human B-cell donations.

We continue to work with multiple U.S government collaborators to evaluate a number of options for the continued evaluation and testing of SAB-185, including advanced clinical development, targeting specialized populations, such as the immune compromised, and alternate routes of administration.

In addition, we will review the data from the Phase 3 portion of the ACTIV-2 program and expect the full data readout for the Phase 2 NIH ACTIV-2 trial to be available Mid-2022.

COVID-19 Background

Coronaviruses are a large family of viruses that can cause illness in animals or humans.

In humans there are several known coronaviruses that cause respiratory infections.

These coronaviruses range from the common cold to more severe diseases such as severe acute respiratory syndrome (SARS-CoV-1), Middle East respiratory syndrome (MERS-CoV), and COVID-19 (SARS-CoV-2).

COVID-19, the disease caused by SARS-CoV-2 and its numerous variants, caused a global pandemic in 2020 that rapidly advanced throughout the world and has resulted in over 435 million cases and more than 5.9 million deaths as of March 1, 2022.

SARS-CoV-2’s genome encodes a spike protein common to all members of the coronavirus family.

Neutralizing antibodies to this spike protein are associated with protection from infection and disease and, as a result, this spike protein is the primary target for currently available vaccines and monoclonal antibodies therapies.

The emergence of several SARS-CoV-2 variants have created significant concern with respect to therapeutics and vaccines to prevent and treat COVID-19.

Some of the variants result in increased transmissibility and have shown resistance to current therapies that rely on neutralizing antibodies.

These variants include the Omicron and Delta variants which have been identified by the Centers for Disease Control and Prevention as Variants of Concern given their potential severity of illness and associated death and their increased transmissibility.

The Centers for Disease Control and Prevention has indicated that some monoclonal antibody treatments may not be as effective against infection with Omicron and the FDA has revoked the emergency use authorization for certain monoclonal antibody therapies.

The FDA’s decision was based on the fact that COVID-19 variants had been shown to be resistant to such therapies, resulting in the increased risk for treatment failure.

The Omicron variant continues to be the dominant variant today.

Certain variants have caused reinfections in individuals with pre-existing antibody responses due to prior infection or vaccination, indicating that pre-existing antibodies do not necessarily fully protect against these variants.

Alternative Treatments and Limitations

Vaccines for Prevention of COVID-19

Several vaccines have been authorized for the prevention of COVID-19 under public health emergency guidelines in the United States and worldwide, including vaccines created by Moderna and Pfizer/BioNTech utilizing mRNA as well as adenovirus-based vaccines developed by AstraZeneca and Janssen (a subsidiary of Johnson and Johnson).

While these vaccines have demonstrated efficacy in preventing COVID-19, we believe that a vaccine alone approach is not going to be fully effective to address the COVID-19 pandemic because of several factors, including:

Current and future variants may be resistant in whole or in part to current vaccines.

Vaccines do not provide immediate protection as the neutralizing antibody response resulting from available vaccines takes approximately 10 to 14 days after the final dose of the vaccine.

Immunocompromised individuals may not respond sufficiently to the neutralizing antibody response of the vaccines because of the limitations inherent in compromised immune systems.

Negative perceptions of vaccine safety continue to prevent a significant portion of the U.S.

and world populations from accepting the vaccine as a safe and effective prophylactic.

The duration of vaccine protection is approximately six months and booster shots are recommended periodically to provide protection against new variants.

Monoclonal Antibodies for Treatment of COVID-19

A small number of monoclonal antibody treatments (either as a monotherapy or a combination cocktail) have been granted emergency use authorization in the United States and are available for use in certain EU member states for the treatment of mild to moderate COVID-19 in certain patient populations.

The recent emergence of several SARS-CoV-2 variants has impacted the efficacy of these treatments and the FDA has revoked the emergency use authorization for certain monoclonal antibody therapies.

The FDA’s decision was based on the fact that COVID-19 variants had been shown to be resistant to such therapies, resulting in the increased risk for treatment failure.

Antiviral Small Molecule Drugs for Treatment of COVID-19

Molnupiravir is a polymerase inhibitor, which works by stopping the virus’s genetic material from being replicated accurately, causing the enzyme that replicates the virus’

RNA to inserts errors or mutations, which then get replicated many times until the virus can no longer survive.

Research suggests drugs similar to molnupiravir can affect other enzymes in the body when given for longer periods of time and was of concern for the 13-10 vote from the FDA advisory committee.

Paxlovid is made up of two components, an experimental molecule called PF-07321332 and a drug called ritonavir, which is also used in some drugs to treat HIV.

Both components are protease inhibitors, meaning they block an enzyme that cuts apart long strands of nonfunctional viral proteins into smaller, functional proteins thus making viral proteins non-functional.

Our Rationale for the Development of SAB-185 Polyclonal Antibody for Treatment of COVID-19

We began development of SAB-185 around the middle of March 2020, when the seriousness of the pending pandemic became evident.

We immediately procured DNA sequences of the full-length spike protein and began DNA immunization of the Tc Bovine.

DNA from the immunizations incorporated into the cells of the Tc Bovine and began producing SARS-CoV-2 Spike Protein that initiated and immune response in the animals.

The animals were immunized twice with the DNA immunization, three weeks apart.

During this time, we developed a full-length spike protein that was delivered to the Tc Bovine three weeks after the second DNA immunization.

Plasma was collected from these animals on day 8, 11, and 14 after this third spike protein immunization.

The plasma was pooled and used as the raw material to purify the anti-SARS-CoV-2 human polyclonal antibodies in our proprietary purification process.

The initial clinical lot was released in June 2020, the pre-clinical studies were completed, and the Initial New Drug Application was filed on July 6, 2020, with FDA agreeing to allow the start of the Phase 1 and Phase 1b clinical trials on July 31, 2020.

Phase 3 Trial

The Phase 3 portion of the NIH ACTIV-2 trial, initiated in in early October, 2021, was designed as a randomized, open-label, active comparator-controlled platform study assessing the clinical safety and efficacy of SAB-185 at a dose of 3,840 unit/kg (approximately 750 mg total dose in a 100 kg human) compared to active control monoclonal cocktail antibody treatment in people with mild to moderate COVID-19 who are at higher risk for progression to hospitalization.

The Phase 3 trial enrolled approximately 750 participants to receive the investigational agent SAB-185 and 750 to receive an active comparator with primary outcome measures including safety and non-inferiority for the prevention of a composite endpoint of either hospitalization or death from any cause through study day 28.

More information on the ongoing Phase 3 trial can be found at the ClinicalTrials.gov website (Identifier:

NCT04518410).

Phase 2 Trial

The Phase 2 portion of the trial for SAB-185 began in the second quarter of 2021.

ACTIV-2 is a COVID-19 master protocol sponsored and funded by the NIH, in collaboration with the AIDS Clinical Trials Group.

The Phase 2 trial was in ambulatory patients, with 110 participants in each of two cohorts, and a control group.

More information can be found at ClinicalTrials.gov website under the identification code NCT04518410.

In September 2021, we announced that the DSMB had completed its prespecified interim analysis data review of the safety and efficacy of SAB-185 in the Phase 2 portion of the NIH ACTIV-2 trial and recommended advancement to Phase 3 based on meeting pre-defined graduation criteria.

Both the lower dose of 3,840 units/kg (approximately 750 mg total dose in a 100 kg human) and the higher dose of 10,240 units/kg (2000 mg total dose in a 100 kg human) of SAB-185 tested in Phase 2 met the pre-defined efficacy goal for advancement to Phase 3 and appeared safe at the interim analysis.

NIH and SAB researchers decided to assess the lower SAB-185 dose in Phase 3.

We expect the full final data readout from the NIH ACTIV-2 Phase 2 trial to be available Mid-2022.

Phase 1 Trials

The Phase 1 trial, started in July 2020, was a randomized, double-blind, placebo-controlled study of four cohorts consisting of a total of 28 subjects, at dose levels of 10 mg/kg, 25 mg/kg, 25 mg/kg on two occasions, or 50 mg/kg of SAB-185, or normal saline.

All subjects have concluded their participation.

A description of this study can be found at the ClinicalTrials.gov website under the identification code of NCT04468958.

The primary endpoint(s) were the incidence and severity of adverse events and Serious Adverse Events (SAEs) or transfusion-related adverse events at day 29.

Secondary endpoints included the incidence and severity of adverse events and SAEs through day 90, among others.

The DSMB monitored adverse events after each cohort was infused.

The DSMB recommended that each later cohort could be infused with the next highest dose according to the study protocol.

No SAB-185-related SAEs were identified by the DSMB, though some anticipated adverse events were noted in both the SAB-185 and placebo participants.

Interim aggregate data from the 10mg/kg and 25mg/kg cohorts from this study, including safety data, were submitted to the FDA.

The Phase 1b trial, started in August 2020, was a randomized, double-blind, placebo-controlled study of three cohorts consisting of a total of 21 subjects, at dose levels of 10 mg/kg, 25 mg/kg, or 50 mg/kg of SAB-185 or normal saline.

A description of this study can be found at the ClinicalTrials.gov website under the identification code NCT04469179.

The primary endpoint(s) were the incidence and severity of adverse events and SAEs or transfusion-related adverse events at day 29.

Secondary endpoints included the incidence and severity of adverse events and SAEs through day 90 and measurement of SARS-CoV-2 quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) results of the naso/oropharynx at various times.

The DSMB 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.

No SAB-185-related SAEs were identified by the DSMB though adverse events were noted in both the SAB-185 and placebo participants.

Interim aggregate data from the 10mg/kg and 25mg/kg cohorts from this study, including safety data, were submitted to the FDA.

After completion of the Phase 1 trials, the FDA allowed SAB-185 to progress into an adaptive COVID-19 Phase 2 as part of the ACTIV-2 master protocol, which can be found at ClinicalTrials.gov website under the identification code NCT04518410, sponsored and conducted by the NIH.

Preclinical Studies

In this study conducted at the University of Pittsburg in 2020, SAB-185 was compared to the highest titer convalescent plasma available using the plaque reduction neutralization titer needed to neutralize 100% of the SARS-CoV-2 virus.

These results suggest that SAB-185 is 40 times more potent than high titer convalescent plasma.

This high titer, target specific human polyclonal antibody is achieved through our hyperimmunization strategy.

These high titer human polyclonal antibodies cannot be achieved with convalescent plasma from human donors.

In this study conducted at Washington University School of Medicine in 2020, we evaluated the ability of three different lots of SAB-185 and an anti-SARS-CoV-2 monoclonal antibody to prevent SARS-CoV-2 escape mutants.

The three different lots of SAB-185 and the monoclonal antibody were serially passaged in the presence of SARS-CoV-2 virus.

As shown, no SAB-185 lots allowed the development of escape mutants.

However, SARS-CoV-2 escape mutants developed in the presence of the monoclonal antibody indicated by the three red arrows, one of which includes an E484K mutant.

This specific mutation that was lab generated is also a currently circulating mutation found in multiple SARS-CoV-2 variants of concern and variants of interest that are infecting humans globally.

Multiple SARS-CoV-2 variants with spike protein mutations have arisen and are infecting humans globally, and their impact on the effectiveness of both vaccines and immunotherapies is a growing concern.

We have been collaborating with the U.S.

Government COVID response throughout 2020 and 2021 to evaluate the ability of SAB-185 to neutralize these mutant strains using a pseudovirion assay developed and conducted at the FDA.

In this study, the inhibitory concentration at 50% of SAB-185 was determined against pseudovirions containing mutations in the spike protein and compared to the wild-type virus, to determine the ratio between the two.

As can be seen on the table above to the left in the IC50 ratio column, no significant impact on the IC50 ratio was observed for any of the tested mutant strains including the current most prevalent strain in the U.S., the Delta variant.

This indicates that SAB-185 is retaining neutralization potency to these existing SARS-CoV-2 variants of concern and potentially future emerging variants.

In addition, specific virus point mutations like the E484K mutation are known to escape some monoclonal antibody therapeutics, which is indicated on the heatmap to the right are all fully neutralized by SAB-185.

In addition, recent data has demonstrated that SAB-185 retains neutralization activity against the Omicron SARS-CoV-2 in an in vitro pseudovirus model.

The data were generated by scientists at the US Food and Drug Administration (FDA) Center for Biologics Evaluation and Research (CBER).

In this study, FDA researchers evaluated SAB-185 using a lentiviral-based pseudovirus assay conducted in a BSL2 environment that incorporates a stable 293T cell line expressing human angiotensin converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2).

The results indicate that SAB-185 retains a potent ability to neutralize recombinant S protein lentiviral pseudovirus that mimics the SARS-CoV-2 Omicron (B.1.1.529) variant.

Although SAB-185 retained potent neutralization of the Omicron variant, it did show a mild-moderate reduction in potency compared to the wild type.

Due to the nature of human polyclonal antibodies, it is important to note that neutralization is only one component of overall efficacy which can potentially provide therapeutic benefit to patients.

For example, polyclonal antibodies can effectively block receptors used for viral entry by binding to multiple epitopes on the receptor binding domain and activation of immune effector cells which are not evaluated in this study.

The versatility of our platform also provides the capability to quickly add strains and adjust to new variants through strain change supplements to our regulatory filings.

SAB-185 Antibody Dependent Enhancement (ADE)

Antibody Dependent Enhancement (ADE) is a poorly understood phenomenon in which a viral disease can become much more severe or lethal after vaccination or after administration of antibodies against a virus.

In the first half of 2020, we investigated the potential of SAB-185 to cause severe disease in a wild-type (WT) ferret model of mild disease after infection with SARS-CoV-2.

Cohorts of WT ferrets (four cohorts, N=3 per cohort) were infused with 1.0, 0.5 and 0.1 mg/kg of SAB-185 (one log range in dose) or normal saline 15 hours prior to infection with a low-passage Munich strain of SARS-CoV-2 and followed for 14 days.

The 1.0, 0.5, and 0.1 mg/kg SAB-185 doses in ferrets were selected to approximate potentially non-neutralizing SAB-185 antibody concentrations that would occur after multiple half-lives after a human received 5 to 20 mg/kg of SAB-185.

The results of the study indicated that SAB-185 treatment of the WT ferret cohorts did not cause acute toxicity, any mortality, or enhanced disease over the course of 14-day study.

All groups and animals had mild disease, though individual animals had variations in measured clinical and scientific parameters.

SAB-185 Tissue Cross Reactivity Study

The objective of this study, conducted in 2020 in preparation for IND submission, was to evaluate the potential cross reactivity of biotinylated SAB-185 with cryosections from a full panel of human tissues.

Two different lots (Lot Nos.

A5303 and A5304) of biotinylated SAB-185 were compared.

In order to detect binding, the biotinylated test articles, designated SAB-185-Bio (Lot No.

A5303) and SAB-185-Bio (Lot No.

A5304), were applied to cryosections of normal human tissues (at least 3 donors per tissue, where available) at two concentrations (35 and 10 µg/mL [Lot No.

A5303] or 35 and 7 µg/mL [Lot No.

In addition, the test articles were substituted with a biotinylated polyclonal human IgG antibody, which has a different immunogenic specificity from that of the test articles, designated HuIgG-Bio (control article).

Other controls were produced by omission of the test or control articles from the assay (assay control).

SAB-185-Bio (both Lot Nos.

A5303 and A5304) produced weak to strong staining of the positive control material (SARS-CoV-2 RBD-His UV-resin spot slides [designated SARS-CoV-2 RBD]) at the higher concentration, with a reduction in staining intensity to weak to moderate at the lower concentration of SAB-185-Bio (Lot No.

A5303) and comparable staining at the lower concentration of SAB-185-Bio (Lot No.

SAB-185-Bio (Lot No.

A5303) and SAB-185-Bio (Lot No.

A5304) did not specifically react with the negative control material (human hypercalcemia of malignancy peptide, amino acid residues 1-34 UV-resin spot slides [designated PTHrP 1-34]) at either staining concentration.

The control article, HuIgG-Bio, did not specifically react with either the positive or negative control materials.

There also was no staining of the assay control slides.

The specific reactions of SAB-185-Bio (Lot No.

A5303) and SAB-185-Bio (Lot No.

A5304) in all staining runs with the positive control material and the lack of specific reactivity with the negative control material, as well as the lack of reactivity of the control article, indicated that the assay was sensitive, specific, and reproducible.

No staining was present with SAB-185-Bio (Lot Nos.

A5303 or A5304) in the human tissue panel examined.

As SAB-185-Bio (Lot Nos.

A5303 or A5304) bind to a viral protein not expected to be expressed in normal human tissues, this result was anticipated.

The results of the ADE and Tissue Cross Reactivity studies were submitted to the FDA for review as part of the IND request.

The FDA allowed us to initiate a Phase 1 trial in healthy adults and a Phase 1b trial in ambulatory adults with confirmed SARS-CoV-2 infection.

SAB-176 (Severe Influenza)

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

SAB-185 was designed and developed without the need for human convalescent plasma or human B-cell donations and has once again demonstrated DiversitAb platform advantage to neutralize multiple pathogen strains mutated overtime without significant loss of potency.

Equally important, the data also confirmed that high-risk patient populations unable to generate a sufficient endogenous immune response may benefit the most from IgG treatments produced by the DiversitAb platform.

Due to COVID-19 market and commercialization uncertainties, we have chosen to pause development of SAB-185.

This program has shown that we can rapidly develop and deliver a clinical trial-ready asset as well as the clear product development, manufacturing, control and regulatory pathway of assets developed from the DiversitAb platform.

Further data and information on this program can be found in the Proprietary DiversitAb Platform Section.

HIGH RISK INFLUENZA

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

This novel, specifically targeted high-potency immunotherapy leverages the natural 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 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 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, to avoid development of resistant strains and to serve as a protective prophylactic in high-risk populations.

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

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.

Influenza Market

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 –

41 million cases of influenza each year, with 140,000 –

710,000 hospitalizations and 12,000 –

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

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.

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.

While the severity of influenza is challenging to forecast year to year, for simplicity’s sake, we assume a consistent incidence rate of 30 million cases in the U.S., within the average range of the last ten years.

In the 2020/2021 influenza season, cases and hospitalizations were down markedly (approximately 60% and 90%, respectively), as many or more of the vulnerable patients contracted COVID, rather than influenza.

In the 2020-2021 influenza season, cases and hospitalizations were down markedly (approximately 60% and 90%, respectively), as many of the vulnerable patients contracted COVID, rather than influenza, and COVID prevention measures stopped the spread of influenza.

It is our expectation that influenza is globally persistent and case rates are expected to come back to historical levels in the coming years.

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annually, about half of which will require a medical visit.

Competition and SAB-176 Value Proposition

Only SAB-176 Provide Potential for “

EVERGREEN ”

Influenza Biologic with Low Risk of Escape Mutants

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.

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).

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.

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

A secondary endpoint 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.

Phase 2a Double-Blind, Placebo-Controlled Study

Secondary end points 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.

A full analysis and data readout is being prepared and expected in the first half of 2022.

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

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

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

Phase 1 Trial

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Preclinical Studies

A pre-clinical study, conducted at Utah State University in 2017, demonstrated the ability of our anti-influenza human antibodies (an earlier, non-optimized candidate designated SAB-149) to produce cross-reactive antibodies to mutating influenza strains we did not initially target.

The panel to the left is phylogenetic tree or ancestral map of the B Yamagata seasonal influenza strain.

Specifically highlighted are the 2013 B/Phuket/ strain used to produce antibodies from our platform and its distant relative from 2006, the B/Florida strain which we used as the challenge strain in a lethal mouse model in the panel to the left.

As shown here, the antibodies provided 100% protection down to 12.5 mg/kg demonstrating cross-protection to current and future emerging flu variants due mutational drift.

This is a potential advantage of polyclonal antibodies and our platform.

Preclinical Study Conducted at Utah State University

A pre-clinical study, conducted at Utah State University in 2017, demonstrated the ability of our anti-influenza human hIgGs (an earlier, non-optimized candidate designated SAB-149) to produce cross-reactive hIgGs to mutating influenza strains we did not initially target.

The panel to the left above is a phylogenetic tree or ancestral map of the B Yamagata seasonal influenza strain.

Specifically highlighted are the 2013 B/Phuket/ strain used to produce hIgGs from our platform and its distant relative from 2006, the B/Florida strain which we used as the challenge strain in a lethal mouse model in the left image of Figure 9.

As shown in Figure 10, the hIgGs provided 100% protection down to 12.5 mg/kg demonstrating cross-protection to current and future emerging flu variants due to mutational drift.

This is a potential advantage of hIgGs and our platform.

SAB-176 Study Conducted at Utah State University

One of the areas of growing concern with small molecule antivirals used to treat influenza is neuraminidase inhibitor resistance.

For this reason, new treatments for influenza are needed.

In this study conducted at the University of Utah in 2019, the in-vivo efficacy of SAB-176 compared to a human-derived antibody product and the small molecule, Oseltamivir was assessed in a lethal mouse model after challenge with an Oseltamivir resistant pandemic H1N1 strain.

In this study conducted at Utah State University in 2019, the in-vivo efficacy of SAB-176 compared to a human-derived antibody product and the small molecule, Oseltamivir was assessed in a lethal mouse model after challenge with an Oseltamivir resistant pandemic H1N1 strain.

Five mg/kg of SAB-176 provided 100% protection while 5, 10 and 20 mg/kg of the human-derived anti-influenza antibody or Oseltamivir did not.

This suggest that SAB-176, at very low doses, could be effective in the treatment of humans infected with neuraminidase resistant or non-resistant H1N1 influenza.

This suggests that SAB-176, at very low doses, could be effective in the treatment of humans infected with neuraminidase resistant or non-resistant H1N1 influenza.

SAB-176 Tissue Cross Reactivity

The objective of this study conducted in 2019 was to determine the potential cross reactivity of biotinylated SAB-176, a polyclonal human IgG antibody directed against influenza virus, with cryosections of human and rabbit (New Zealand White) tissues.

To detect binding, the biotinylated test article, designated SAB-176-Bio, was applied to cryosections of normal human tissues (at least three donors per tissue, where available) and rabbit tissues (at least two animals per tissue, where available) at two concentrations (20 and 2 µg/mL).

In addition, the test article was substituted with a biotinylated human IgG antibody, which has a different immunogenic specificity from that of the test article, designated HuIgG-Bio (control article).

The objective of this study conducted in 2019 was to determine the potential cross reactivity of biotinylated SAB-176, a polyclonal human hIgG antibody directed against influenza virus, with cryosections of human and rabbit (New Zealand White) tissues.

In addition, the test article was substituted with a biotinylated human hIgG antibody, which has a different immunogenic specificity from that of the test article, designated HuIgG-Bio (control article).

Other controls were produced by omission of the test or control articles from the assay (assay control).

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SAB-176-Bio did not specifically react with the negative control material (human hypercalcemia of malignancy peptide, amino acid residues 1-34, UV-resin spot slides [designated PTHrP 1-34]) at either staining concentration.

The control article, HuIgG-Bio, did not specifically react with either the positive or negative control materials.

The control article, HuIgG-Bio, did not specifically react with either the positive or negative control materials.

There also was no staining of the assay control slides.

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The results were submitted to the FDA for review as part of the IND submission.

SAB-142 (Organ Transplant & Type 1 Diabetes)

We are currently advancing therapeutic candidates through its SAB-142 program for organ transplant induction and organ transplant rejection, as well as a related program to address T1D.

We are also conducting an undisclosed autoimmune target research effort under a research collaboration agreement with CSL Behring.

The collaboration is exploring the potential of new therapies to treat challenging autoimmune and idiopathic diseases using polyclonal antibodies generated by our DiversitAb platform.

We are sharing research program and related costs with CSL Behring.

The collaboration may lead to subsequent development and commercialization agreements.

Potentially Significant Opportunity in Transplant

CLOSTRIDIOIDES DIFFICILE (C.DIFF) INFECTION (CDI)

SAB-195 is the first in class fully human hIgG treatment for treatment of CDI

We are currently advancing our top-priority preclinical therapeutic candidate, SAB-195, a high-unmet medical need asset for treatment of CDI-associated diarrhea and reduction in recurrence of CDI.

CDI is a bacterial infection of the large intestine.

A spectrum of clinical disease ranges from mild to very severe infection characterized by abdominal pain, fever, diarrhea, nausea, and vomiting.

Complications of severe CDI include kidney failure, toxic megacolon, bowel perforation, and death.

Epidemiology data support high unmet medical needs globally

CDI is one of the most prevalent healthcare–associated bacterial infections in the U.S.

and developed world.

CDC estimates that there are ~ 500,000 infections per year and >30,000 deaths from CDI in the U.S.

CDI is associated with significant costs:

Up to $4.8 billion each year in excess health care costs for acute care facilities alone.

Patients with the first CDI recurrence have a risk of subsequent recurrence from 25% to 40% and higher.

CDI-attributable median length of stay and costs (in US$) increased from 7 (4-13) days and $13,168 ($7,525-$24,456) for patients with primary CDI only to 15 (8-25) days and $28,218 ($15,050-$47,030) for patients with recurrent CDI.

The risk of death for patients with recurrent CDI is 33% higher compared to those patients without recurrence.

While treatments exist, they are associated with high rates of recurrent CDI that are even more difficult to treat than primary infection.

It is also well known that antibiotics, the current standard of care treatment for CDI, are associated with emergence of bacterial resistance.

Finally, fecal transplants, last-line treatment of CDI, may be associated with a risk of transmitting infectious agents as they are manufactured from human fecal matter, and many are contraindicated in immuno-compromised patients.

That triple mechanism of action –

diff spores, vegetative cells, and multiple types of toxins –

not only comprehensively target the entire complex life-cycle of this pathogen, but also aim to provide superior efficacy in reducing infection recurrence, hospitalizations, and hospitalization duration of hospital stay.

Only SAB-195 Can Target Multiple CDI Bacterial Antigens and Toxins in One Therapeutic

Preclinical proof of principle data of DiversitAb platform in CDI

Available preclinical data indicates that SAB-195 will deliver on its product value proposition to target multiple antigens including vegetative state of bacteria and toxins from multiple strains.

The data was published in the peer-reviewed journal “Vaccine.”

Fully human polyclonal antitoxin hIgGs were produced in the DiversitAb platform by immunizing transgenic bovine with 4 fusion proteins representing several types of toxins from different C.

diff strains.

In a hamster CDI model presented on this slide, hamsters treated with human antitoxin hIgG were protected when challenged with historical (left image of Figure 12) or epidemic strains of C.diff as presented in the right image of Figure 12.

All animals in the control group died within 24 to 48 hours following challenge, while 40% treated with 10 mg hIgG and 90–100% treated with 60 mg hIgGs survived the 8-day observation period.

SAB-195 Preclinical Data

Clinical Development Path

We plan to file an IND in first quarter 2024 and subsequently have topline results from Phase 1 and Proof of Biological activity available in 2024.

Confirmation of SAB-195 antibacterial effects and good microbiome-sparing effects are highly critical for prevention of CDI recurrence.

Following such confirmations and the subsequent initiation of the dose-range finding Phase 2b trial in 2024, we would expect top line results to be available by the end of 2025.

TYPE 1 DIABETES

We are currently advancing therapeutic candidates through its SAB-142 program aimed at delaying the onset and progression of T1D.

SAB-142 is a multi-indication potential asset also being developed for organ transplant induction and organ transplant rejection among other immunological indications.

Therapeutic Potential in New-Onset Type 1 Diabetes

A potentially significant application for SAB-142 is for the delay or prevention of the onset of T1D, a serious lifelong autoimmune disease.

T1D affects 1.6 million people and there are 60,000+ new diagnoses each year in the U.S.

The full potential of agents such as Thymoglobulin to delay or prevent T1D is limited by the unsuitability of animal products for repeat dosing.

SAB-142 represents an opportunity to offer a novel fully-human alternative to rabbit- or equine-derived ATG IgGs, which has the potential for re-dosing and avoids current risk factors such as serum sickness, anaphylaxis, and loss of efficacy of currently available therapies.

Based on results of a Phase 2 clinical trial conducted by Dr.

Michael Haller at the University of Florida, a single dose of rabbit ATG (Thymoglobulin) showed sustained benefit in T1D over two years by maintaining significantly higher C-peptide levels (a marker of pancreatic beta cell function) than placebo controls.

However, more than 65% of treated patients in this study acquired serum sickness due to infusion of an animal antibody (rather than human) that included rash, 3-4 days of malaise, fever, and joint swelling.

The symptoms often required treatment with steroids that impair diabetes management and reduces capacity to give the rabbit ATG again as C-peptide levels begin to drop as shown in Figure 13 below.

In addition to potentially preserving beta cell function in early T1D patients, a human ATG like SAB-142 could open the possibility of re-dosing when clinically meaningful indicators such as C-peptide levels and glycosylated hemoglobin blood tests indicate worsening disease, without the potential risk of inducing the major immune reactions that can occur with fully-animal IgGs (See Figure 14).

Rabbit ATG Study for Type 1 Diabetes

Competition and SAB-142 Value Proposition

SAB-142 is the Only Fully-Human IgG Anti-Thymocyte Globulin showing the

Same In-Vitro Mode of Action as Low Dose Rabbit ATG

Preclinical Studies for SAB-142

We have completed the GLP toxicology results that enable filing an IND submission.

Figure 14 shows lymphocyte cell population comparing SAB-142 to one of the approved and commercially available animal ATG products.

Following administration of 5mg/kg animal ATG and 1mg, 5mg/kg, and 10mg/kg SAB-142 to treatment-naive non-human primates, immuno-profiling analysis of two top SAB-142 dose-levels shows significant reduction of lymphocytes vs baseline.

While both SAB-142 and animal ATG induced substantial lymphocyte reduction, the dynamics of such depletion show more prolonged effects with SAB-142 treatment.

These in vivo results strongly suggest that SAB-142 may have efficacy attributes desired for numerous auto-immune indications including but not limited to T1D, organ transplant induction and maintenance therapy, aplastic anemia among others while having the impactful product advantage of an improved safety profile. 

IND filing is anticipated on or before the first quarter of 2024.

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 & immunogenicity profile of SAB-142

GLP-tox study demonstrated SAB-142 is well tolerated at escalating doses tested

Both SAB-142 and its active control, an FDA-approved rabbit-derived ATG, induced transient and prolonged lymphodepletion for the duration of the study.

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

SAB-142 GLP Toxicology Study Results Enable IND Submission

Potentially Significant Opportunity in Transplant and Other Immunological Diseases

SAB-142 is a fully-human anti-thymocyte globulin (ATG) candidate for preventing organ transplant rejection.

Current approved ATG products are sourced from animals, including transplant market leader rabbit-derived Thymoglobulin, and equine-derived ATGAM.

A human ATG alternative has the potential for higher potency without toxicity, presenting a potential opportunity to redefine the standard of care.

Dosing advantages of a human ATG may include a longer half-life and potential for repeat dosing, without significant potential to generate serum sickness or anaphylaxis, which can be caused by the presence of animal proteins in the current therapies.

A human ATG alternative has the potential for higher potency without toxicity, presenting an opportunity to redefine the standard of care.

Dosing advantages of a human ATG may include a longer half-life and potential for repeat dosing, without significant potential to generate serum sickness or anaphylaxis, which can be caused by the presence of animal proteins in the current therapies. 

Despite broad use, there are several limitations of approved ATG products.

7 unchanged sentences

We expect to show improved safety, dosing, and efficacy profiles for our human ATG program in future human studies.

This is a flow cytometry analysis of a gated lymphocyte cell population comparing SAB-142 to the two FDA approved and commercially available rabbit and horse ATG products on the market.

As you can see, SAB-142 binds to the same T-cell population as both rabbit and horse ATG antibodies, suggesting comparable mode of action.

SAB-142 Flow Cytometry Analysis

Figure 16 provides a flow cytometry analysis of a gated lymphocyte cell population comparing SAB-142 to the two FDA approved and commercially available rabbit and horse ATG products on the market.

As you can see, SAB-142 binds to the same T-cell population as both rabbit and horse ATG IgGs, suggesting comparable mode of action.

SAB 142 Study –

Mode of Action Against T-Cell Subsets

We further explored the mode of action of SAB-142 against T-cell subsets.

SAB-142 had higher CD8 killing activity compared to the rabbit antibody and had similar performance in survival of T-regulatory cells, induction of activated CD4 T Cells, and reduction of naïve CD4 cells.

These in vitro results strongly suggest that SAB-142 may have the potency attributes needed for transplant induction and rejection therapy while having the impactful product advantage of an improved safety profile.

These in vitro results strongly suggest that SAB-142 may have the potency attributes needed for transplant induction and rejection therapy while having the impactful product advantage of an improved safety profile.

The product attributes of SAB-142 are potentially also well aligned to address the desired safety profile of ATG treatments that have been shown to be beneficial in treating T1D.

Therapeutic Potential in New-Onset Type 1 Diabetes

A potentially significant application for SAB-142 is for the delay or prevention of the onset of T1D, a serious lifelong autoimmune disease.

T1D affects 1.6 million people and there are 60,000+ new diagnoses each year in the U.S.

The full potential of agents such as Thymoglobulin to delay or prevent T1D is limited by the unsuitability of animal products for repeat dosing.

SAB-142 represents an opportunity to offer a novel fully human alternative to rabbit- or equine-derived ATG antibodies, that has the potential for re-dosing and avoids current risk factors such as serum sickness, anaphylaxis, and loss of efficacy of currently available therapies.

Based on results of a Phase 2 clinical trial conducted by Dr.

The symptoms often required treatment with steroids that worsens diabetes management and reduces capacity to give the rabbit ATG again as C-peptide levels begin to drop as shown in the graph below.

We have commenced initial IND-enabling studies.

we plan to initiate additional IND-enabling studies for SAB-142 in the fourth quarter of 2022, pending availability of appropriate study models.

AUTOANTIBODY IMMUNE DISORDERS

DiversitAb Platform Anti-Idiotype Proof of Principle in Autoimmune Disease

Figure 18 shows recent data on using the DiversitAb platform to produce Anti-idiotype hIgGs to treat auto-antibody mediated immune disease such as System Lupus Erythematosus (SLE) or Scleroderma.

Known mAb autoantibodies were selected and used as antigens for hyperimmunization in Tc bovine.

One was an IgG1 isotype and the other an IgG4 isotype.

Tc bovine derived hIgGs against these autoantibodies were produced and purified.

Anti-Variable/Anti-Idiotype hIgGs are Specific to the Variable Region

This in-vitro data for Tc bovine hIgGs produced to both autoantibodies in a single Tc bovine shows the percent of inhibition of binding to the variable regions of both the IgG1 and IgG4 auto-antibodies.

Controls showed the specificity of binding to the variable regions indicated by the lack of inhibition of binding to the Fc fragments of each antibody as well as the mAb framework of each of the autoantibodies.

As an example, this polyclonal mechanism of action of these Tc bovine derived hIgGs is differentiated from current treatments of autoantibody mediated disease like Systemic Lupus Erythematosus by presumably NOT causing general immune suppression nor suppression of all B-cells but by actively suppressing or eliminating specific autoreactive antibodies and B cell clones, and through polyclonality and somatic hypermutation, have activity against mutated antibodies and their B-cell clones.

This approach has the potential further benefit of extending remission without immune suppression.

We are very excited to continue to explore this novel approach using the DiversitAb Platform with proven ability to produce antibodies to multiple human antigen targets including autoreactive antibodies.

ONCOLOGY (Undisclosed Targets)

We have the potential to develop polyclonal therapeutic candidates that address multiple aspects of cancer.

We are pursuing undisclosed target opportunities for which we expect to release early developmental data in the second quarter of 2022.

We believe that the DiversitAb platform may to lead to oncology applications for our polyclonal antibodies because of our potential to address mutations, polymorphisms, and resistance pathways.

Our human polyclonal antibodies may offer advantages as cancer therapies, including:

Multi-targeting –

Ability to simultaneously target multiple modalities of cancer in a single product.

Multivalency –

Leverages native immune response –

polyclonal antibodies –

with binding to multiple epitopes to address mutations.

Metastasis Prevention –

Literature suggests human polyclonal IVIG antibodies may help prevent tumor metastases.

Effector Function –

Enhanced effector functions such as antibody-dependent cellular cytotoxicity and complement dependent cytotoxicity.

Replicability –

Developed antibodies against a variety of oncology targets using our DiversitAb platform.

We have recruited and deployed an oncology-focused team with the goal of pioneering polyclonal antibodies for use in treating cancer.

We have filed several patent applications and expect to demonstrate initial proof-of-principle in oncology in the second quarter of 2022.

We have the potential to develop IgG therapeutic candidates that address multiple aspects of cancer.

We are pursuing undisclosed target opportunities for which we expect to release early developmental data in the fourth quarter of 2023.

We believe that the DiversitAb platform may lead to oncology applications for our IgGs because of our potential to address mutations, polymorphisms, and resistance pathways.

Our human IgGs may offer advantages as cancer therapies, including:

Multi-targeting – Ability to simultaneously target multiple modalities of cancer in a single product.

Multivalency – Leverages native immune response – IgGs – with binding to multiple epitopes to address mutations.

Metastasis Prevention – Literature suggests human polyclonal IVIG may help prevent tumor metastases.

Effector Function – Enhanced effector functions such as antibody-dependent cellular cytotoxicity and complement dependent cytotoxicity.

Replicability – Developed IgGs against a variety of oncology targets using our DiversitAb platform.

We have recruited and deployed an oncology-focused team with the goal of pioneering human IgGs for use in treating cancer.

We have filed several patent applications and expect to demonstrate initial proof-of-principle in oncology in the fourth quarter of 2023.

Proprietary DiversitAb Platform Overview

Our proprietary DiversitAb platform gives us the unique ability to generate targeted, fully-human hIgGs without the need for human donors or plasma.

These diverse and high-potency IgGs can be targeted to viruses, bacteria, toxins, and human immunogen targets.

The current platform 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 human immunoglobulins (hIgGs).

The novel capability of the DiversitAb platform uses the natural human biological immune response that makes our platform well-suited to address multiple therapeutic categories, presenting potential opportunities for new therapies to address unmet medical needs.

Figure 20 below depicts the main elements of product development and manufacturing using our DiversitAb platform.

Development and Manufacturing Using DiversitAb ™

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

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

Develop Immunogen for Disease Target .

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

The 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 fully-human IgGs, and then hyperimmunized with the 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.

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 platform is replicable and scalable since the Tc Bovine are all clones.

If more plasma is needed, more animals can be produced through cloning technology and plasma fractionation is 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 have successfully utilized our DiversitAb platform 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.

We have vertically integrated the platform technology across a significant series of value inflection points.

Our capabilities include advanced animal reproduction methods (cloning) to produce Tc Bovine, animal husbandry, immunogen or antigen development, plasma collection, plasma purification, drug substance manufacturing and product fill/finish, nonclinical and clinical study management, quality assurance, quality control, regulatory compliance, and program collaboration.

This work has generated a technology which allows collaborating companies that may be unfamiliar with animal production systems or plasma fractionation processes to partner with us in the development and commercialization of products derived from the DiversitAb platform with confidence in the CMC and regulatory pathways that have been established.

Scaled Infrastructure & Capacity:

Tc Bovine & Plasma Production Facility

Scaled Infrastructure & Capacity:

Laboratory & Manufacturing

Fully Human Target Specific High Potency IgGs

Our novel multivalent IgG approach, including hyperimmunization of the Tc Bovine results in specifically targeted, highly potent, high-avidity, broadly diverse, fully human IgGs, overcoming the challenges and exceeding the capabilities of traditional animal and human-derived IgGs.

Animal-derived IgGs, such as from horses or rabbits, have the disadvantage of being immunogenic in humans, and they often cause severe hypersensitivity reactions, limiting their clinical use for repeat dose administration.

Human-derived IgGs are limited by the difficulty of collecting IgGs from humans and the inability of humans to produce IgGs to endogenous proteins under normal circumstances.

In addition, only our proprietary process of hyperimmunization of the Tc Bovine can yield high target potency as demonstrated in Figure 23 below where SAB-185 potency was superior to the highest titer convalescent plasma.

SAB 185 Study - Neutralization Evaluation Conducted at The University of Pittsburgh

In this study conducted at the University of Pittsburgh in 2020, SAB-185 was compared to the highest titer convalescent plasma available using the plaque reduction neutralization titer needed to neutralize 100% of the SARS- CoV-2 virus.

These results suggest that SAB-185 is 40 times more potent than high titer convalescent plasma.

This high titer, target-specific human IgG is achieved through our hyperimmunization strategy.

These high-titer human IgGs cannot be achieved with convalescent plasma from human donors.

Natural Multivalent and Effector Function Properties of IgGs

Nature has spent millions of years evolving the sophisticated mammalian innate and adaptive immune system to protect humans and all other mammals against disease.

We have harnessed that nature by design through our DiversitAb platform to produce our fully-human IgG therapeutics and by doing so have intentionally harnessed the competitive advantage of the natural properties of a polyclonal immunoglobulin to protect against highly mutating or evolving pathogens or disease targets like a cancer that fully activates our body’s own immune system in a target-specific way.

Our IgGs are engineered to primarily produce the IgG1 isotype, and to a lesser extent the IgG2 isotype, and have fully functional unmodified antibody variable regions (or Fab domains) that specifically bind to target antigens that provide natural multivalent properties.

This multiepitope targeting neutralizes highly mutating targets and prevents mutation escape.

The broad diversity of the Fab domains also contain the natural mixture of high and low affinity binding IgGs referred to as avidity and have fully functional IgG Fc domains that further activate the native human immune system by activating effector cells.

We believe there is a demonstrable and significant potential advantage of Tc Bovine-produced human IgGs in their ability to bind to both foreign exogenous or human endogenous protein targets, activate human effector cells, and not cause hypersensitivity reactions.

Multivalent properties of our Tc Bovine Derived hIgGs

Figure 24 shows preclinical data demonstrating the multivalent properties of our hIgGs for SAB-185, an anti-SARS-CoV-2 hIgG therapeutic that has shown broad neutralization potency to recent SARS-CoV-2 variants that have emerged over the COVID-19 pandemic, which including the Delta and Omicron variants.

In vitro Neutralization Against VSV-SARS-CoV-2 Mutants

We collaborated with the U.S.

Government COVID response team throughout 2020 and 2021 to evaluate the ability of SAB-185 to neutralize these mutant strains using a pseudovirus assay developed and conducted by scientists at the US Food and Drug Administration ("FDA") Center for Biologics Evaluation and Research (CBER).

In this study, FDA researchers evaluated the inhibitory concentration at 50% of SAB-185 against lentiviral-based pseudovirions containing mutations in the spike protein representative of the Alpha, Delta, Lambda, and Omicron (B.1.1.529) SARS-CoV-2 variants.

This assay incorporates a stable 293T cell line expressing human angiotensin converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2).

The results in Figure 24 above demonstrate that SAB-185 effectively neutralizes all tested recombinant S protein lentiviral pseudoviruses that mimics the SARS-CoV-2 variants.

Although SAB-185 retained potent neutralization of the Omicron variant, it did show a mild-to-moderate reduction in potency compared to the Alpha wild type.

In vitro Neutralization Against Clinical SARS-CoV-2 Isolates

In Figure 25 we further expanded our analysis to a broader panel of pandemic SARS-CoV-2 variants, specifically the Omicron lineage that emerged in 2022 which contained novel mutations that rendered many of the existing monoclonal antibody therapeutics ineffective.

In this study, we collaborated with the Center for Vaccine Research and Department of Immunology at the University of Pittsburgh (UPITT) to evaluate the ability of SAB-185 to neutralize clinically isolated SARS-CoV-2 variants using a Vero hAce2/TMPRSS2 cell plaque reduction neutralization assay.

SAB-185 retained potent neutralization to all variants despite a reduction of activity against the Omicron lineage.

Due to the nature of SAB-185 fully human IgGs, it is important to note that neutralization of viral entry into the cell as measured in Figure 24 and Figure 25 is only one component of the overall efficacy measurement for a polyclonal antibody therapeutic.

SABs hIgGs contain a fully human antibody Fc domain that activates the immune system through effector functions that kill the virus, so SAB-185 efficacy is not just measured by effective blocking of the RBD used for viral entry but activating immune effector functions that target and kill the virus.

This in combination with the fact that SAB-185 targets multiple epitopes spanning the entire surface of the spike protein including the RBD means that changes observed in neutralization activity due to specific mutations in the RBD should not significantly impact the overall efficacy of SAB-185 as a therapeutic.

This is not the case for mAbs that targeted a single epitope on the spike protein as viral mutations spanning the single binding site could result in complete loss of blocking virus entry (neutralization) and/or complete loss of efficacy as effector functions are no longer possible which is exactly what transpired for many of the mAb therapeutics during the pandemic.

To demonstrate the competitive advantage of our hIgGs and measure the full therapeutic potential of SAB-185 against clinical isolates of the SARS-CoV-2 variants, we collaborated with UPITT and Utah State University (USU) to perform an in-vivo efficacy study using a human ACE2 (hACE2) transgenic Syrian hamster model (Figure 26).

This hamster model exhibits rapid lethality after intratracheal SARS-CoV-2 challenge with the Munich, Alpha, Beta, Delta, and D144-146 variants;

the Omicron B.1.1529 variant resulted in a delayed, less severe and non-lethal disease similar to what is observed in the clinic with the Omicron variants.

As can be seen detailed in Figure 26 and Figure 27 below, prophylactic treatment with SAB-185 provided 100% protection from death and minimized clinical signs of infection when challenged with six clinical isolates of the SARS-CoV-2 variant viruses including the Omicron variant.

Although reduced in vitro neutralization activity was observed with Delta and Omicron variants, SAB-185 was still highly protective at human-relevant doses in vivo .

Therefore, reduced in vitro neutralization titers of SAB-185 against SARS CoV-2 variants were not associated with any reduction of in vivo efficacy.

SAB-185 protection from mortality in hACE2 hamsters challenged with six variant SARSCoV-2 isolates

Figure 26 shows data on hamsters that were administered SAB-185 (50mg/kg) or PBS intramuscularly and then challenged intratracheally 24 hours later with 1000 plaque forming units of variant viruses.

Mortality for individual variant PBS controls (A) and for combined (all SARS-CoV-2 variants tested) PBS control versus SAB-185 treated groups (B).

Individual mortality data for Munich (C), D144-146 (D) Alpha (E), Beta (F), Delta (G), and Omicron (H) viruses.

Mantel-Cox log-rank significance is indicated within each panel.

*p<0.05, **p<0.01, ***p<0.005.

SAB-185 protection from clinical signs in hamsters challenged with six variant SARSCoV-2 isolates

Figure 27 shows data presented as the inverse of the clinical score sum values.

Each data point represents an average of morning and afternoon observations.

A) Clinical sign scoring for individual hamsters in all groups.

B) Combined clinical sign scoring data for SAB-185-treated and control hamsters.

(C) Combined clinical sign scoring data for SAB-185-treated and control hamsters on D5 (last day all animals were alive) post challenge or D8 post challenge for Omicron-infected animals (peak clinical signs).

Individual clinical sign scoring data for Munich (D), D144-146 (F) Alpha (H), Beta (J), Delta (L) and Omicron (N) viruses.

Individual clinical sign scoring data for Munich (E), D144-146 (G) UK (I), SA (K), Delta (M) and Omicron (O) variants on D5 (last day all animals were alive) post challenge or D8 post challenge for Omicron (peak clinical signs).

* p<0.05, **p<0.01, ***p<0.005.

Open circles are surviving (controls and Omicron) and the SAB-185 treated animal that exhibited delayed replication (data not shown).

The multivalent competitive advantages of our hIgGs have the potential to prevent escape mutations that could arise from natural selective pressures of a highly mutating communicable disease like COVID-19 or therapeutic selective pressure where mutations arise from an inferior monovalent targeted treatment regimen like a single monoclonal antibody or small molecule.

To further support this point the preclinical data in Figure 28 and Figure 29 below demonstrates the ability of our hIgG therapeutics to potentially prevent mutation escape and protect against new mutations that may arise due to natural or monovalent drug induced selective pressure.

This unfortunately played out with the COVID-19 pandemic, where monovalent monoclonal antibody treatments as single or in combination were reported to have lost significant neutralization activity against the highly mutating SARS-CoV-2 variants like Omicron.

SAB-185 Study Conducted at Washington University School of Medicine

The study represented in Figure 28 was conducted at Washington University School of Medicine in 2020, we evaluated the ability of three different lots of SAB-185 and an anti-SARS-CoV-2 monoclonal antibody (2H04) to prevent SARS-CoV-2 escape mutants.

The three different lots of SAB-185 and the monoclonal antibody were serially passaged in the presence of SARS-CoV-2 virus.

As shown, no SAB-185 lots allowed the development of escape mutants.

However, several SARS-CoV-2 escape mutants developed in the presence of the monoclonal antibody indicated by the three red arrows in Figure 28 above, one of which included a E484K mutant.

This specific mutation that was lab generated was also a naturally circulating mutation found in multiple SARS-CoV-2 variants of concern and variants of interest that were infecting humans globally.

SAB-159 Study

Figure 29 above demonstrates the potential therapeutic advantage of our IgGs to effectively neutralize highly mutating pathogens such as Hantaan viruses.

A study conducted in 2019 demonstrated SAB-159, an anti-Hantaan hIgG, completely neutralized the original wild-type virus, as well as both single mutants, and a double mutant of Hantaan virus.

Effective neutralizing potency is indicated by the low in vitro IC50 threshold concentration below 100ng/mL indicated by the small grey area at the bottom of Figure 29.

In contrast, two neutralizing mAbs alone or in combination could not completely neutralize the two different mutations individually or in combination.

Effector Functions of our hIgGs

hIgGs specifically bind to antigens through their variable regions, but also, depending on their specific hIgG isotype, activate effector functions via their Fc domains.

Native humoral immune responses against pathogens or target antigens do not consist of a single antibody, but of complex hIgGs composed of multiple affinity matured hIgGs binding to numerous epitopes.

The binding of polyclonal hIgG’s to multiple epitopes aids in eliciting the activation of innate host effector mechanisms, such as antibody dependent-cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) and antibody-dependent cellular phagocytosis (ADCP).

As mentioned previously our DiversitAb produced hIgG therapeutics also contain a fully functional antibody Fc domain that is unmodified and naturally diverse as well.

This fully functional Fc domain allows for effector cell engagement and activation as demonstrated in the data presented below.

Activation of Human Effector Cell Function

In Figure 30 above, the lines with solid black and white circles represent monocyte and neutrophil phagocytosis in Figure A and Figure B and Natural Killer cell degranulation in Figure C from the serum of two Tc Bovines hyperimmunized with Ebola glycoprotein on eight occasions.

The blue and purple bars represent two Tc Bovine human IgG lots produced from their plasma after the third and fourth immunizations and from the sixth, seventh and eighth immunizations respectively.

The red and white bars represent a naïve Tc Bovine human IgG and normal saline respectively.

The green and orange bars represent two anti-Ebola glycoprotein monoclonals.

As can be seen, both lots of anti-Ebola Tc Bovine human IgGs demonstrated the ability to induce monocyte and neutrophil cell phagocytosis and Natural Killer cell degranulation.

The lot produced from plasma after the sixth to the eighth immunization had better activity and is consistent with avidity maturation of the IgGs.

In contrast, while the monoclonals induced monocyte phagocytosis, only one was able to induce neutrophil phagocytosis.

And critically, neither monoclonal antibody had the ability to induce Natural Killer cell degranulation.

This demonstrates that Tc Bovine-produced human IgGs induce human effector cells which are critically important to the control of viruses, bacteria, and other pathogens.

Multitarget Immunoglobulin Diversity in a Single Vial Designed to Effectively Treat Complex Disease

Another key product differentiator of our hIgGs 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 natural 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.

We believe single or combinatorial monoclonal antibody therapies are significantly challenged to reproduce this competitive product advantage.

Replicating this hIgG product attribute is costly and challenging for mAbs due to constraints adhering to the full factorial clinical trial design requirements by CDER where dosing two mAbs targeting separate epitopes for a combinatorial product is challenging enough let alone potentially hundreds of epitopes to multiple antigen targets covered by a hIgG therapeutic.

In addition, mAbs are specifically at risk regarding the treatment of highly mutating disease targets such as upper respiratory viral infections like Influenza or COVID-19, complex bacterial infections (like C.

), or anti-microbial resistant bacteria, highly complex immune diseases like Type 1 diabetes, or highly mutating cancers.

This risk was realized for monoclonal antibody therapy during the COVID-19 pandemic where single and combinatorial mAb therapies were reported to have lost significant neutralizing activity against highly mutating SARS-CoV-2 viruses.

A multi-target approach was used to produce SAB-176 developed to target both Type A and Type B seasonal influenza strains, and data demonstrating the multi-target neutralization from cross protective IgGs to non-targeted influenza strains like pandemic H1N1 (pH1N1) is shown in the Figure 31 below.

The competitive advantage of this multi-target product approach for SAB-176 was further supported with our Phase 2a challenge trial where the primary endpoint was met by significantly reducing the viral load of patients challenged with pH1N1 influenza.

The versatility of this multitarget approach can be further expanded with a strain add approach, where new seasonal strains are included in the production of SAB-176.

This will maintain or expand the broad neutralization capability to both current and future seasonal influenza variants, and potentially extend to pandemic outbreaks.

This strain add approach was implemented in producing SAB-176 for our Phase 2a challenge trial, where two influenza seasonal vaccines were used.

This seasonal strain add approach simply requires strain add supplements to our regulatory filings.

We have additionally implemented this similar multi-target approach to produce our current preclinical pipeline products SAB-195 and SAB-142.

SAB-176 Study

Hemagglutination Inhibition (HAI) titers of SAB-176 and anti-Flu human IVIG (hIVIG) are reported against the individual viruses indicated in the heading with color coded for specific annual flu season vaccines.

Three lots of anti-Flu human IVIG were cGMP manufactured from the pooled human plasma selected with high anti-Flu HAI titers in 2013, 2017 and 2018, respectively.

SAB-176 was purified from Tc Bovine plasma vaccinated with the 2018-19 flu season vaccine strains.

As shown in Figure 31 above, SAB-176 had higher HAI titers than anti-Flu hIVIG against seasonal flu vaccine strains and demonstrates the broad neutralization capability to past & future non-vaccine or non-targeted strains including the pandemic H1N1 strain.

Rapid Product Development Capability with Proven Regulatory Pathway

A final key differentiator is embedded in our polyclonal development approach that leverages our DiversitAb platform to capture discovery and production efficiencies not available to mAb product development.

Through the utilization of our Tc Bovine, we are able to 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 cGMP product 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 FDA.

The FDA regulates polyclonal hIgGs and mAbs completely differently as mAbs are regulated through CDER and pAbs through CBER.

CBER has approved over 40 IgG products from human- and animal-derived plasma and is very familiar with our DiversitAb platform and pAb product.

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

In combination with our rapid product development and vertically integrated process we have demonstrated our ability to file and IND in 128 days from product concept and rapidly advance through the clinic.

Proven DiversitAb Platform Product Development Versatility

Overview of Our In-Vivo Animal Data From 2008 to 2018

Figure 32 provides an overview of our in vivo animal data from 2008 to 2018 that has enabled several pre-clinical studies with efficacy data demonstrating the broad potential of the DiversitAb platform to address diverse human diseases, globally.

As shown in Figure 32, infectious disease has been a strategic proving ground for the validation of our platform.

Listed above are several significant human diseases for which adequate countermeasures may not exist.

These include Ebola, Middle East respiratory syndrome coronavirus (MERS-CoV), and Zika, among others.

Clinically Validated Across Several Targets Spanning Ph1 to Ph3 Clinical Trials

Initial Demonstration of Human Efficacy and Multi-Dosing Capability

Demonstration of Human Efficacy and Multi-Dosing Capability

Figure 33 depicts a small efficacy trial in a single patient who had an antibiotic-resistant mycoplasma hominus infection.

Conducted in 2017 at Brigham and Women’s Hospital, this study showed an initial indication of efficacy in Tc Bovine-derived anti-Mycoplasma human hIgGs in an immunosuppressed 68-year- old man diagnosed with a M.

hominis septic polyarthritis who developed a chronically draining right hip fistula following a failed hip replacement surgery.

The fistula is shown on the far-left image in Figure 33.

He was treated with human-derived intravenous immunoglobulin and antibiotics for seven years during which time the mycoplasma became multi-antibiotic resistant.

At the request of the patient and his physician, we produced the anti-mycoplasma human IgG therapeutic, which was intravenously administered to the subject at doses up to 100 mg/kg as shown in the center image of Figure 32.

This was done under an FDA allowed Phase 1b study.

The human hIgG product was well tolerated, and the subject’s mycoplasma load fell to undetectable levels with rapid healing and closure of the fistula as shown on the far-right image in Figure 33.

The patient then elected to undergo a repeat hip replacement surgery and he developed a Staphylococcus Aureus and other bacteria wound infection including mycoplasma.

The patient was then re-treated with the Tc Bovine- derived human IgGs which resulted in marked reductions in mycoplasma load as shown in the center table.

This remarkable case study demonstrates the potential utility of Tc Bovine-derived human hIgGs to treat serious antibiotic resistant infections in general, but also the potential opportunity to produce specific human IgG therapeutics to treat individuals with intractable infections using a personalized medicine approach.

We have performed multiple clinical trials demonstrating safety in hundreds of patients and have demonstrated proof of concept for our DiversitAb platform in the clinic that includes three SAB-sponsored INDs and one CTA (filed Ex-US) that encompass seven clinical trials from Phase 1 to Phase 3 across treatment of three indications (MERS, Influenza, and COVID-19) briefly summarized below.

First-in-Man Clinical Safety and Efficacy

The first-in-human clinical trial of SAB-301for MERS-CoV, conducted in 2017 and sponsored by the NIH, evaluated safety of this Tc Bovine-derived human IgGs.

The conclusion was that SAB-301 was safe and well tolerated.

Pharmacokinetic analysis demonstrated a half-life of the anti-MERS-CoV human IgGs of 28 1/2 days, which is the reported half-life of human-derived hIgGs in humans.

Importantly, anti-drug antibodies, or antibodies to ligands used in our DiversitAb purification process, or anti-bovine plasma protein antibodies were not detected.

SAB-176 (anti-Influenza) Advanced through a Phase 2a Challenge Trial

Our SAB-176 program is a multitarget anti-influenza product that specifically targets both Type A and Type B seasonal influenza strains.

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 study in 60 healthy adults that were challenged with a pandemic influenza virus strain (pH1N1).

The primary endpoint of the study was achieved despite the fact that SAB-176 was not produced specifically targeting the pH1N1 strain.

This was not only a successful Phase 2a for our influenza program but demonstrated in a human study the multivalent competitive advantage of our DiversitAb produced hIgGs as cross protective IgGs generated from our multitarget seasonal Type A and Type B influenza product, SAB-176 met the primary end point criteria of significantly reducing patient pH1N1 influenza viral load.

Our SAB-176 program is further detailed in the Pipeline section above.

SAB-185 Study - Double-Blind Study in Ambulatory Adults

Figure 34 above presents a randomized double-blind study in ambulatory adults with confirmed SARS-CoV-2 infection with symptoms less than 7 days.

110 were randomized to low dose, 110 randomized to high dose, and 110 to placebo.

The graduation criteria to the Phase 3 portion of this adaptive phase 2/3 study included a minimum posterior probability of reducing nasopharyngeal qRT-PCR of > 0.5 log compared to placebo by at least 0.6.

Both doses exceeded this criterion at day 3.

A post hoc sub-analysis showed that pronounced reductions in NP viral load was only observed in high-risk patients (obesity, chronic illness, etc.).

This suggests that similar reductions in lung viral load could also occur and possibly provide protection against progression to pneumonia and/or severe disease.

Government Contracts and Collaborations

We have collaborated extensively with U.S.

Government agencies within both the Department of Defense (DOD) and the U.S.

Government agencies within both the U.S.

Department of Defense ("DoD") and the U.S.

Department of Health & Human Services (HHS).

We are executing an award from Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense (JPEO –

CBRND) Joint Project Lead for Enabling Biotechnologies (JPL-EB) (hereafter JPEO-EB) within the DOD that includes co-funding from the Defense Health Authority and from BARDA (within HHS).

The award currently totals up to approximately $200 million.

The scope of the award includes proof-of-concept, scaling and live-fire of a Rapid Response Antibody Program leveraging our response capabilities and was expanded to include our COVID-19 therapeutic, SAB-185, as part of the Countermeasures Acceleration Group (formerly Operation Warp Speed).

We executed an award from Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense (JPEO - CBRND) Joint Project Lead for Enabling Biotechnologies (JPL-EB) (hereafter JPEO-EB) within the DoD that includes co-funding from the Defense Health Authority and from BARDA (within HHS).

The award totaled approximately $200 million.

The scope of the award included proof-of-concept, scaling and live-fire of a Rapid Response Antibody Program leveraging our response capabilities and was expanded to include our COVID-19 therapeutic, SAB-185, as part of the Countermeasures Acceleration Group (formerly Operation Warp Speed).

That expansion included significant capacity growth, addition of capabilities, and expansion of infrastructure including human resources and facilities.

The use of SAB-185 in the ACTIV-2 trial is sponsored, funded and conducted by the NIH and we are not required to bear any of the costs of this clinical trial.

On August 3, 2022, we received notice from the DoD terminating the JPEO Rapid Response contract.

No termination penalties were incurred by SAB in connection with the termination.

SAB received two final payments from the U.S.

Government for work performed and winddown activities on this award in November 2022 and January 2023 which totaled approximately $16.8M.

Manufacturing Strategy

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

a 50L scale cGMP suite that has produced clinical grade drug product, and a 200L scale clean room that was completed in 2021 and is currently being validated to produce clinical grade drug substance and drug product.

The 200L facility is expected to generate drug product in 2022.

In addition, we maintain substantial laboratory facilities and operations in Sioux Falls, South Dakota for product development and testing, quality control and discovery.

We recently initiated our own internal immunogen development capabilities and significantly scaled production capacity to accommodate the Tc Bovine immunizations required for SAB-185 production.

We have also recently initiated an expansion of our research and development laboratory facilities to accommodate expansion in oncology research, clinical testing, and discovery.

Our Tc Bovine are housed at dedicated specialty facilities that cater to the production, health, safety, and welfare of the animals, and provide plasma production at commercial scale for our products.

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 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 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 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.

Animals donate plasma three times per month (2.1% of bodyweight each time).

To produce more product, more animals must be immunized for a target.

Advanced clinical product for SAB-185 was produced at CSL Behring.

We are presently engaged in discussions with additional third-party contract manufacturers to manufacture commercial drug substance and drug product at commercial scale.

To produce more product, more animals are added to the program and immunized to the target.

The biopharmaceutical industry is highly competitive and subject to rapid and significant technological change as research provides a deeper understanding of the pathology of diseases and new technologies and treatments are developed.

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 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.

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.

These competitors also compete with us in recruiting and retaining qualified clinical, regulatory, scientific, sales, marketing, and management personnel, in establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs.

Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.

We face competition from pharmaceutical, biotechnology and other companies that have or are pursuing the development of antibody treatments, including Adagio Therapeutics, Inc., AstraZeneca plc, Brii Biosciences Limited, Celltrion Healthcare Co, Ltd., Eli Lilly and Co, GlaxoSmithKline, Regeneron Pharmaceuticals, Inc.

and Vir Biotechnology, Inc.

In addition, we may face competition from many established pharmaceutical companies focused on developing vaccines, oral antivirals, and other therapeutics.

Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.

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 antibodies 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 IgGs 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.

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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.

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 fully human antibodies at commercial scale.

For more information, please see “Risk Factors –

Risks Related to Our Intellectual Property.”

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

We expect our global patent protection to extend beyond 2033 with respect to producing commercial scale human antibodies using our chromosome engineering that generates high concentrations of human antibodies in ungulates.

However, we recognize that the area of patent and other intellectual property rights in biotechnology is an evolving one with many risks and uncertainties, which may affect those rights.

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

As of December 31, 2021, our patent portfolio includes over 40 issued patents or pending applications in 12 patent families.

We have made strategic filings in jurisdictions in jurisdictions include the United States, Australia, Canada, China, Europe, France, Germany, Japan, Korea, New Zealand, United Kingdom, Hong Kong, India, Mexico and Russia, in these 12 patent families.

Our technologies may be difficult to replicate, creating potential barriers to entry, as our genetic engineering know-how and suite of proprietary 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 human IgGs using our chromosome engineering that generates high concentrations of human IgGs 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.

As of December 2022, our patent portfolio includes over 40 issued patents or pending applications.

We have made strategic filings in jurisdictions including the United States, Australia, Canada, China, Europe, Japan, Korea, and Mexico.

These patent families cover:

Granted patents to produce a transgenic bovine (expiring in 2021, but also covered by granted patents within the portfolio that continue to protect the technology with advancements made to the production system including expirations as late as 2033).

Granted patents for genetically modified non-human mammals (e.g., bovines and other ungulates), and methods of making these mammals (latest ones expiring in 2033).

Granted patents relating to transgenic ungulate embryos of one or more cells that have a human chromosome fragment, and methods for making them (expiring in 2025).

Granted patents 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 relating to large-scale production of human antibodies by transgenic animals with high production of fully human IgG of at least 1 g/L in sera (expiring in 2031).

Granted patents covering methods for cloning non-human mammals that allow the donor chromosomes or donor cells to be reprogrammed prior to insertion into an enucleated oocyte dominancy (expiring in 2023).

Granted patent covering a method for producing human antibodies 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 2035).

Granted patents covering cloned transgenic ungulates (e.g., bovines) in which prion protein activity is reduced by one or more genetically engineered mutations (expiring in 2023).

Related to anti-thymocyte globulin (ATG) products, a pending international patent application covering ungulate-derived polyclonal immunoglobulin compositions comprising fully human or substantially human immunoglobulins that specifically bind human thymocytes, T cells, B cells, and/or monocytes, and methods of making and using the same (expiring in 2041).

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 (expiring in 2023 and 2025).

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

A granted U.S.

patent relating to reprogramming a call to express a T-cell receptor reactive with an antigen of interest (expiring in 2025).

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).

patents covering cloned transgenic ungulates (e.g., bovines) in which prion protein activity is reduced by one or more genetically engineered mutations (expiring in 2023 and 2025).

Related to anti-thymocyte globulin (ATG) products, pending patent applications in the U.S., Europe, Japan, and other major markets covering ungulate-derived polyclonal immunoglobulin compositions comprising fully human or substantially human immunoglobulins that specifically bind human thymocytes, T cells, B cells, and/or monocytes, and methods of making and using the same in treating or preventing organ transplant rejection or type 1 diabetes (if issued, naturally expiring in 2041).

Pending international and U.S.

patent applications covering ungulate-derived human immunoglobulins that specifically bind coronavirus S protein, and methods of making and using the same intreating or preventing coronavirus disease (expiring in 2041).

An international patent application covering ungulate-derived human immunoglobulins that specifically bind Epidermal Growth Factor Receptor (EGFR), and methods of making and using the same in treating or preventing cancer (expiring in 2041).

An international patent application covering ungulate-derived polyclonal immunoglobulin compositions comprising human immunoglobulins that specifically bind Programmed Death-Ligand 1 (PD-L1), and methods of making and using the same in treating or preventing cancer (expiring in 2041).

patent applications covering ungulate-derived human immunoglobulins that specifically bind coronavirus S protein, and methods of making and using the same in treating or preventing coronavirus disease (if issued, naturally expiring in 2041).

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).

Our proprietary know-how and trade secrets include the following:

Complex chromosome engineering trade secrets not disclosed in patent applications.

Complex chromosome engineering trade secrets.

Immunogen dose levels used for nucleotides, peptides, proteins, closely autologous proteins, virus particles, whole inactivated viruses, cell membranes, whole cells, bacteria, glycol-proteins, human cell immunogens, tissue preparation.

Our adjuvants formulations for immunogen hyperimmunization.

Bovine plasma fractionation procedures and trade secrets contained within our proprietary Standard Operating Procedures.

Bovine plasma fractionation procedures and trade secrets contained within our proprietary Standard Operating Procedures.

Animal husbandry procedures for human antibody-producing ungulates.

Transgenic neo-natal ungulate IVIG administration for failure of passive immunity.

Certain cell culture and cloning practices not disclosed in patents.

Plasma collection procedures not disclosed in publications and patents.

The term of any individual patent depends upon the legal term of the patent in the country or countries (or jurisdiction, e.g., the European Union) in which it is obtained.

Patent Regulatory Regime

Certain cell culture and cloning practices.

Plasma collection procedures.

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.

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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 of a patent that covers an FDA-approved drug 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.

In the United States, the patent term of a patent 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.

The Hatch-Waxman Act permits a patent term extension of up to five years beyond the expiration of the patent.

The length of the patent term extension is related to the length of time the drug is under regulatory review.

Patent term extension cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval, only one patent applicable to an approved drug may be extended and only those claims covering the approved drug, a method for using it, or a method for manufacturing it may be extended.

Similar provisions are available in Europe and other foreign jurisdictions to extend the term of a patent that covers an approved drug.

In the future, if and when our products receive FDA approval, we expect to apply for patent term extensions on patents covering those products.

Patent term extension cannot extend the remaining term of a patent beyond a total of 14 years from the date of product licensure, only one patent applicable to a licensed biologic may be extended and only those claims covering the licensed biologic, a method for using it, or a method for manufacturing it may be extended.

Similar provisions are available in Europe and other foreign jurisdictions to extend the term of a patent that covers a licensed biologic.

In the future, if and when our product candidates.

Receive FDA approval or licensure, we expect to apply for patent term extensions on patents covering those products.

We expect to seek patent term extensions to any of our issued patents in any jurisdiction where these are available, however there is no guarantee that the applicable authorities, including the FDA in the United States, will agree with our assessment of whether such extensions should be granted, and if granted, the length of such extensions.

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Advice of counsel and our business model and needs are always considered.

We file patents containing claims for protection of all useful applications of our proprietary technologies and any products, as well as all new applications and/or uses we discover for existing technologies and products, assuming these are strategically valuable.

We file patents containing claims for protection of useful applications of our proprietary technologies and products, as well as new applications and/or uses we discover for existing technologies and products, assuming these are strategically valuable.

We may periodically reassess the number and type of patent applications, as well as the pending and issued patent claims to ensure that coverage and value are obtained for our processes, and compositions, given existing patent law and court decisions.

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Consequently, we may not obtain or maintain adequate patent protection for any of our future product candidates or for our technology platform.

We cannot predict whether the patent applications we are currently pursuing will issue as patents in any particular jurisdiction or whether the claims of any issued patents will provide sufficient proprietary protection from competitors.

We cannot predict whether the patent applications we are currently pursuing will be issued as patents in any particular jurisdiction or whether the claims of any issued patents will provide sufficient proprietary protection from competitors.

Any patents that we hold may be challenged, circumvented, or invalidated by third parties.

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The Hatch-Waxman Amendments permit a patent restoration term of up to five years as compensation for patent term lost during the product development and FDA regulatory review process.

However, patent term restoration cannot extend the remaining term of a patent beyond a total of 14 years from the product’s approval date.

The patent term restoration period generally is one-half the time between the effective date of an IND and the submission date of a biologics license application (BLA) less any time the sponsor did not act with due diligence during the period, plus the time between the submission date of a BLA and the approval of that application less any time the sponsor did not act with due diligence during the period.

Only one patent applicable to an approved biological product is eligible for the extension, only those claims covering the approved drug, a method for using it or a method for manufacturing it may be extended and the application for the extension must be submitted prior to the expiration of the patent.

However, patent term restoration cannot extend the remaining term of a patent beyond a total of 14 years from the product’s approval or licensure date.

The patent term restoration period generally is- once the patent issues- one-half the time between the effective date of an IND and the submission date of a biologics license application ("BLA") less any time the sponsor did not act with due diligence during the period, plus the time between the submission date of a BLA and the approval of that application less any time the sponsor did not act with due diligence during the period.

Only one patent applicable to an approved biological product is eligible for the extension, only those claims covering the licensed biologic, a method for using it or a method for manufacturing it may be extended and the application for the extension must be submitted prior to the expiration of the patent.

Moreover, a given patent may only be extended once based on a single product.

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Government Regulation

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

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

Additionally, in manufacturing our product candidates, we alter the genomic DNA in animals, and FDA considers such altered genomic DNA in an animal to be a new animal drug, which require submission and approval of a New Animal Drug Application (NADA) prior to being marketed in the United States.

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The requirements governing development and approval of a new animal drug are analogous to those for new human drugs.

A NADA must generally be accompanied by payment of a substantial user fee and must contain substantial evidence of the safety and effectiveness of the new animal drug as well as detailed descriptions of the methods used in and the facilities and controls used for the manufacturing, processing and packaging of the new animal drug to enable FDA to reach a determination that such methods, facilities and controls are adequate to preserve the identify, strength, quality and purity of the new animal drug.

A NADA must generally be accompanied by payment of a substantial user fee and must contain substantial evidence of the safety and effectiveness of the new animal drug as well as detailed descriptions of the methods used in and the facilities and controls used for the manufacturing, processing and packaging of the new animal drug to enable FDA to reach a determination that such methods, facilities and controls are adequate to preserve the identify, strength, quality and purity of the new animal drug.

Further, when FDA reviews and approves a NADA, FDA generally conducts a review of environmental risks pursuant to the requirements of the National Environmental Policy Act (NEPA), if any and where required.

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21 CFR 514.1(b)(14).

GE animal applications have to be evaluated to determine whether such an application individually or cumulatively affects the environment (i.e., whether an extraordinary circumstance exists).

GE animal applications have to be evaluated to determine whether such an application individually or cumulatively affects the environment (i.e., whether an extraordinary circumstance exists).

21 CFR 25.21.

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The current expectation is to have the NADA completed by the fourth quarter of 2024.

We are also currently filing a new animal drug application (NADA) assessing the safety and effectiveness of the genetic modifications to the Tc Bovine animals with the CVM.

We are also currently filing a new animal drug application (NADA) assessing the safety and effectiveness of genetic modifications to the Tc Bovine animals with the CVM.

This is a one-time process that includes future post approval responsibilities related to the durability of animal health and antibody response.

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The process of obtaining regulatory approvals and the subsequent compliance with appropriate federal, state, local and foreign statutes and regulations require the expenditure of substantial financial resources and time.

Multiple polyclonal and monoclonal antibody products have been approved by the FDA to prevent or treat human diseases.

Though the FDA regulates both monoclonals and polyclonal antibody products, Monoclonal antibodies are regulated by the Center for Drug Evaluation and Research (CDER).

Multiple immunoglobulin and monoclonal antibody products have been approved by the FDA to prevent or treat human diseases.

Though the FDA regulates both monoclonal antibodies and immunoglobulin products, Monoclonal antibodies are regulated by the Center for Drug Evaluation and Research (CDER).

A monoclonal antibody is characterized by its molecular structure.

This approach is similar to the process that CDER uses to regulate small molecule drugs.

Because monoclonals are designed to bind to a single epitope, mutation is a significant concern due to selective pressure.

Polyclonal antibodies derived from animals or humans are regulated by the Center for Biologics Evaluation and Research (CBER).

CBER has currently approved over thirty polyclonal products for commercial sale.

Human and animal-derived polyclonals are characterized by their in vitro potency and not by the molecular structure of each antibody in the product.

This approach is similar to the process that CDER uses to regulate small molecule drugs.

Because mAbs are designed to bind to a single epitope, mutation is a significant concern due to selective pressure.

IgGs derived from animals or humans are regulated by the Center for Biologics Evaluation and Research (CBER).

CBER has currently approved thirty-nine unique immunoglobulin products for commercial sale.

Human and animal-derived IgGs are characterized by their in vitro potency and not by the molecular structure of each antibody in the product.

Development Process.

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The process required by the FDA before a biologic product may be marketed in the United States is generally well documented.

In the case of a product that is developed from animals with intentionally altered genomic DNA as the donor material source, the process is more complex and involves both CVM, to oversee the intentionally altered genomic DNA in animals and the Office of Tissues and Advanced Therapies (OTAT) at FDA’s Center for Biologics Evaluation and Research (CBER) to oversee the polyclonal antibody products.

However, this is a onetime process for our Tc bovine and does not have to be repeated for subsequent products produced by the Tc bovine containing the same HAC.

Key aspects of the process include the following:

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submission to CVM of an application for an INAD, which must become effective before human clinical trials may begin;

completion of nonclinical laboratory tests and animal studies according to Good Laboratory Practices (GLPs), and the Animal Welfare Act administered and enforced by the U.S.

Department of Agriculture;

preparation of clinical trial material in accordance with Good Manufacturing Practices (GMPs);

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satisfactory completion of an FDA inspection prior to a BLA approval of the manufacturing facility or facilities where the biologic product is produced to assess compliance with GMPs to assure that the facilities, methods, and controls are adequate to preserve the biologic’s identity, strength, quality and purity;

potential FDA audit of the nonclinical and clinical study sites that generated the data in support of the NADA and BLA;

potential FDA Advisory Committee meeting to elicit expert input on critical issues, including a vote by external committee members;

FDA review and approval of the NADA and BLA, which may be performed in parallel, but the NADA must be granted before a final decision can be made on the BLA, resulting in the licensure of the biological product for commercial marketing;

compliance with any post-approval requirements, including the potential requirement to implement a Risk Evaluation and Mitigation Strategy (REMS), and the potential requirement to conduct post-approval studies.

compliance with any post-approval requirements, including the potential requirement to implement a REMS, and the potential requirement to conduct post-approval studies.

Before testing any biologic product candidate in humans, the product candidate enters the preclinical testing stage.

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Prior to beginning the first clinical trial with a product candidate developed from an animal with altered genomic DNA in the United States, an INAD must be submitted to CVM and an IND must be submitted to CBER, and the FDA must allow the INAD and IND to proceed.

INAD submission is a one-time process and doesn’t have to be repeated with our investigational products for each IND submission for products produced by Tc Bovine with the same HAC.

An INAD and IND are exemptions from the FD&C Act that allow an unapproved product candidate to be shipped in interstate commerce for use in an investigational clinical trial and a request for FDA allowance that such investigational product may be administered to humans in connection with such trial.

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IRBs are charged with protecting the welfare and rights of study participants and consider such items as whether the risks to individuals participating in clinical trials are minimized and are reasonable in relation to anticipated benefits.

The IRB also approves the form and content of the informed consent that must be signed by each clinical trial subject or his or her legal representative and must monitor the clinical trial until completed.

Additionally, some trials are overseen by an independent group of qualified experts organized by the trial sponsor, known as a data safety monitoring board or committee.

Additionally, some trials are overseen by an independent group of qualified experts organized by the trial sponsor, known as a data safety monitoring board or committee.

Human clinical trials are typically conducted in three sequential phases that may overlap or be combined:

The biologic product is initially introduced into healthy human subjects and tested for safety.

In the case of some biologic products for rare diseases, the initial human testing is often conducted in patients.

The biologic product is initially introduced into healthy human subjects and tested for safety. In the case of some biologic products for rare diseases, the initial human testing is often conducted in patients.

The biologic product is evaluated in a limited patient population to identify possible adverse effects and safety risks, to preliminarily evaluate the efficacy of the biologic product for specific targeted diseases and to determine dosage tolerance, optimal dosage, and dosing schedule.

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The FDA may refuse to file any application that it deems incomplete or not properly reviewable at the time of submission and may request additional information.

In this event, the application must be resubmitted with the additional information.

In this event, the application must be resubmitted with additional information.

The resubmitted application also is subject to review to determine if it is substantially complete before the FDA accepts it for filing.

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Under the performance goals and policies implemented by the FDA under the Animal Drug User Fee Act (ADUFA) for original NADAs, the FDA targets 180 days from the submission date in which to complete its initial review and act on a standard application.

A NADA is considered incomplete if it would require additional data or information to enable the FDA to complete and reach a decision on issues presented in the NADA.

A NADA is considered incomplete if it requires additional data or information to enable the FDA to complete and reach a decision on issues presented in the NADA.

Once the sponsor reactivates the NADA by addressing identified deficiencies, the FDA targets 135 to 180 days, depending in part on whether the deficiencies are identified as not substantial or substantial, respectively, to complete its review and respond to the applicant.

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The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.

During the biological product approval process, the FDA also will determine whether a Risk Evaluation and Mitigation Strategy (REMS) is necessary to assure the safe use of the biological product.

During the biological product approval process, the FDA also will determine whether a REMS is necessary to assure the safe use of the biological product.

If the FDA concludes a REMS is needed, the sponsor of the BLA must submit a proposed REMS;

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Additionally, before approving a BLA, the FDA will typically inspect one or more clinical trial sites to assure that the clinical trials were conducted in compliance with IND study requirements and GCP requirements.

To assure GMP and GCP compliance, an applicant must incur significant expenditure of time, money, and effort in the areas of training, record keeping, production and quality control.

To ensure GMP and GCP compliance, an applicant must incur significant expenditure of time, money, and effort in the areas of training, record keeping, production and quality control.

After the FDA evaluates a NADA or BLA and conducts inspections of manufacturing facilities where the investigational product and/or its drug substance will be produced, the FDA may issue an approval letter or for an NADA and BLA respectively, an Incomplete Letter or a Complete Response Letter.

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Further, for biological products, the FDA may impose restrictions and conditions on product distribution, prescribing, or dispensing in the form of a REMS, or otherwise limit the scope of any approval.

The FDA may require one or more Phase 4 post-market studies and surveillance to further assess and monitor the biological product’s safety and effectiveness after commercialization and may limit further marketing of the product based on the results of these post-marketing studies.

The FDA may require one or more Phase 4 post-market studies and surveillance to further assess and monitor the biological product’s safety and effectiveness after commercialization and may limit further marketing of the product based on the results of these post-marketing studies.

Post-Approval Requirements

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Any agency or judicial enforcement action could have a material adverse effect.

Biological product manufacturers and other entities involved in the manufacture and distribution of approved biological products are required to register their establishments with the FDA and certain state agencies and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with GMPs and other laws.

Biological product manufacturers and other entities involved in the manufacture and distribution of approved biological products are required to register their establishments with the FDA and certain state agencies and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with GMPs and other laws.

Accordingly, manufacturers must continue to expend time, money, and effort in the areas of production and quality control to maintain GMP compliance.

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The FDA may withdraw approval of a drug or indication approved under accelerated approval if, for example, the confirmatory trial fails to verify the predicted clinical benefit of the product.

Moreover, under the Food and Drug Administration Safety and Innovation Act enacted in 2012, a sponsor can request designation of a product candidate as a “breakthrough therapy.”

Moreover, under the FDA Safety and Innovation Act enacted in 2012, a sponsor can request designation of a product candidate as a “breakthrough therapy.”

A breakthrough therapy is defined as a drug or biological product that is intended, alone or in combination with one or more other drugs or biologics, to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the drug or biological product may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.

Breakthrough therapy designation comes with all the benefits of fast-track designation, which means that the sponsor may file sections of the BLA for review on a rolling basis if certain conditions are satisfied, including an agreement with the FDA on the proposed schedule for submission of portions of the application and the payment of applicable user fees before the FDA may initiate a review.

Breakthrough therapy designation comes with all the benefits of fast-track designation, which means that the sponsor may file sections of the BLA for review on a rolling basis if certain conditions are satisfied, including an agreement with the FDA on the proposed schedule for submission of portions of the application and the payment of applicable user fees before the FDA may initiate a review.

Drug and biological products designated as breakthrough therapies are also eligible for accelerated approval.

The FDA must take certain actions, such as holding timely meetings and providing advice, intended to expedite the development and review of an application for approval of a breakthrough therapy.

Even if a product qualifies for one or more of these programs, the FDA may later decide that the product no longer meets the conditions for qualification that the time period for FDA review or approval will not be shortened.

Even if a product qualifies for one or more of these programs, the FDA may later decide that the product no longer meets the conditions for qualification and the time period for FDA review or approval will not be shortened.

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.

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The orphan drug designation does not convey any advantage in, or shorten the duration of, the regulatory review or approval process.

If a product that has orphan drug designation subsequently receives the first FDA approval for the disease for which it has such designation, the product is entitled to orphan drug exclusive approval (exclusivity), which means that the FDA may not approve any other applications, including a full BLA, to market the same biologic for the same indication for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity.

If a product that has orphan drug designation subsequently receives the first FDA approval for the disease for which it has such designation, the product is entitled to orphan drug exclusive approval (exclusivity), which means that the FDA may not approve any other applications, including a full BLA, to market the same biologic for the same indication for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity.

Orphan drug exclusivity does not prevent FDA from approving a different drug or biologic for the same disease or condition, or the same drug or biologic for a different disease or condition.

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with an FDA-licensed reference biological product via an approved BLA.

Biosimilarity to an approved reference product requires that there be no differences in conditions of use, route of administration, dosage form and strength and no clinically meaningful differences between the biological product and the reference product in terms of safety, purity, and potency.

Biosimilarity to an approved reference product requires that there be no differences in conditions of use, route of administration, dosage form and strength and no clinically meaningful differences between the biological product and the reference product in terms of safety, purity, and potency.

Biosimilarity is demonstrated in steps beginning with rigorous analytical studies or “fingerprinting,”

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The requirements and process governing the conduct of clinical studies are to a significant extent harmonized at the European Union level but could vary from country to country.

In all cases, the clinical studies are conducted in accordance with GCP and the applicable regulatory requirements and the ethical principles that have their origin in the Declaration of Helsinki.

On January 31, 2022, the European Union's (EU's) Clinical Trial Regulation (Regulation (EU) No 536/2014) became effective.

In all cases, the clinical studies are conducted in accordance with GCP and the applicable regulatory requirements and the ethical principles that have their origin in the Declaration of Helsinki.

On January 31, 2022, the European Union’s (EU’s) Clinical Trial Regulation (Regulation (EU) No 536/2014) became effective.

The Regulation harmonizes the assessment and supervision processes for clinical trials throughout the European Union via a Clinical Trials Information System, which contains a centralized European Union portal and database.

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regulatory regime largely mirrors that of the European Union.

For other countries outside of the European Union, such as countries in Eastern Europe, Latin America or Asia, the requirements governing the conduct of clinical studies, product licensing, pricing and reimbursement vary from country to country.

European Union, such as countries in Eastern Europe, Latin America or Asia, the requirements governing the conduct of clinical studies, product licensing, pricing and reimbursement vary from country to country.

In all cases, again, the clinical studies are conducted in accordance with GCP and the applicable regulatory requirements and the ethical principles that have their origin in the Declaration of Helsinki.

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In the United States, these laws include, without limitation, state and federal anti- kickback, false claims, physician transparency, and patient data privacy and security laws and regulations, including but not limited to those described below.

The federal Anti-Kickback Statute, which prohibits, among other things, persons and entities from knowingly and willfully soliciting, offering, paying, receiving or providing any remuneration (including any kickback, bribe, or certain rebate), directly or indirectly, overtly or covertly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase, order or recommendation of, any good or service, for which payment may be made, in whole or in part, under a federal healthcare program such as Medicare and Medicaid;

The federal Anti-Kickback Statute, which prohibits, among other things, persons and entities from knowingly and willfully soliciting, offering, paying, receiving or providing any remuneration (including any kickback, bribe, or certain rebate), directly or indirectly, overtly or covertly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase, order or recommendation of, any good or service, for which payment may be made, in whole or in part, under a federal healthcare program such as Medicare and Medicaid;

a person or entity need not have actual knowledge of the federal Anti-Kickback Statute or specific intent to violate it in order to have committed a violation.

The term “remuneration”

has been broadly interpreted to include anything of value;

The term “remuneration” has been broadly interpreted to include anything of value;

Federal false claims and false statement laws, including the federal civil False Claims Act, prohibit individuals or entities from, among other things, knowingly presenting, or causing to be presented, to the federal government, claims for payment or approval that are false, fictitious or fraudulent;

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or knowingly concealing or knowingly and improperly avoiding or decreasing an obligation to pay money to the federal government.

Manufacturers can be held liable under the FCA even when they do not submit claims directly to government payors if they are deemed to “cause”

the submission of false or fraudulent claims.

In addition, the government may assert that a claim that includes items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the civil False Claims Act.

The FCA also permits a private individual acting as a “whistleblower”

to bring actions on behalf of the federal government alleging violations of the FCA and to share in any monetary recovery.

Manufacturers can be held liable under the FCA even when they do not submit claims directly to government payors if they are deemed to “cause” the submission of false or fraudulent claims.

The FCA also permits a private individual acting as a “whistleblower” to bring actions on behalf of the federal government alleging violations of the FCA and to share in any monetary recovery.

When an entity is determined to have violated the federal civil False Claims Act, the government may impose civil fines and penalties for each false claim, plus treble damages, and exclude the entity from participation in Medicare, Medicaid and other federal healthcare programs;

The federal civil monetary penalties laws, which impose civil fines for, among other things, the offering or transfer or remuneration to a Medicare or state healthcare program beneficiary if the person knows or should know it is likely to influence the beneficiary’s selection of a particular provider, practitioner, or supplier of services reimbursable by Medicare or a state health care program, unless an exception applies;

The Health Insurance Portability and Accountability Act of 1996, or HIPAA, created additional federal criminal statutes that prohibit among other actions, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, including private third-party payors, knowingly and willfully embezzling or stealing from a healthcare benefit program, willfully obstructing a criminal investigation of a healthcare offense, or falsifying, concealing or covering up a material fact or making any false, fictitious, or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services;

HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009, or HITECH, and their respective implementing regulations, impose, among other things, specified requirements on covered entities and their business associates relating to the privacy and security of individually identifiable health information including mandatory contractual terms and required implementation of technical safeguards of such information.

HITECH also created new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates in some cases, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorneys’

fees and costs associated with pursuing federal civil actions;

made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors) and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members.

The Health Insurance Portability and Accountability Act of 1996, ("HIPAA"), created additional federal criminal statutes that prohibit among other actions, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, including private third-party payors, knowingly and willfully embezzling or stealing from a healthcare benefit program, willfully obstructing a criminal investigation of a healthcare offense, or falsifying, concealing or covering up a material fact or making any false, fictitious, or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services;

HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009, or HITECH, and their respective implementing regulations, impose, among other things, specified requirements on covered entities and their business associates relating to the privacy and security of individually identifiable health information including mandatory contractual terms and required implementation of technical safeguards of such information.

HITECH also created new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates in some cases, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorneys’ fees and costs associated with pursuing federal civil actions;

The federal Physician Payments Sunshine Act requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to report annually to CMS information related to payments or other “transfers of value” made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors) and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members.

Beginning in 2022, applicable manufacturers also will be required to report such information regarding payments and transfers of value provided during the previous year to physician assistants, nurse practitioners, clinical nurse specialists, anesthesiologist assistants, certified nurse anesthetists and certified nurse-midwives;

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Additionally, we may be subject to state laws that require pharmaceutical companies to comply with the federal government’s and/or pharmaceutical industry’s voluntary compliance guidelines and state laws that require drug and biologics manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures, as well as state and foreign laws governing the privacy and security of health information, many of which differ from each other in significant ways and often are not preempted by HIPAA.

Additionally, to the extent that any of our products, if approved, are sold in a foreign country, we may be subject to similar foreign laws.

Additionally, to the extent that any of our product candidates if approved, are sold in a foreign country, we may be subject to similar foreign laws.

The scope and enforcement of each of these laws is uncertain and subject to rapid change in the current environment of healthcare reform, especially in light of the lack of applicable precedent and regulations.

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In recent years, Congress has considered reductions in Medicare reimbursement levels for drugs and biologics administered by physicians.

CMS also has authority to revise reimbursement rates and to implement coverage restrictions for some drugs and biologics.

CMS also has authority to revise reimbursement rates and to implement coverage restrictions for some drugs and biologics.

Cost reduction initiatives and changes in coverage implemented through legislation or regulation could decrease utilization of and reimbursement for any approved products.

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Among other things, the ACA expanded manufacturers’

rebate liability under the Medicaid Drug Rebate Program by increasing the minimum Medicaid rebate for both branded and generic drugs and biologics, expanded the 340B program, and revised the definition of average manufacturer price (AMP), which could increase the amount of Medicaid drug rebates manufacturers are required to pay to states.

rebate liability under the Medicaid Drug Rebate

Program by increasing the minimum Medicaid rebate for both branded and generic drugs and biologics, expanded the 340B program, and revised the definition of average manufacturer price (AMP), which could increase the amount of Medicaid drug rebates manufacturers are required to pay to states.

The legislation also extended Medicaid drug rebates, previously due only on fee-for-service Medicaid utilization, to include the utilization of Medicaid managed care organizations as well and created an alternative rebate formula for certain new formulations of certain existing products that is intended to increase the amount of rebates due on those drugs.

On February 1, 2016, CMS issued final regulations to implement the changes to the Medicaid Drug Rebate program under the ACA.

On February 1, 2016, CMS issued final regulations to implement the changes to the Medicaid Drug

Rebate program under the ACA.

These regulations became effective on April 1, 2016.

Since that time, there have been significant efforts to modify or eliminate the ACA.

For example, the Tax Cuts and Jobs Act ("Tax Act"), enacted on December 22, 2017, repealed the shared responsibility payment for individuals who fail to maintain minimum essential coverage under section 5000A of the Internal Revenue Code of 1986, as amended ("Code"), commonly referred to as the individual mandate.

For example, the Tax Cuts and Jobs Act (“Tax Act”), enacted on December 22, 2017, repealed the shared responsibility payment for individuals who fail to maintain minimum essential coverage under section 5000A of the Internal Revenue Code of 1986, as amended (“Code”), commonly referred to as the individual mandate.

Other legislative changes have been proposed and adopted since passage of the ACA.

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Such scrutiny has resulted in several recent congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, reduce the cost of drugs under Medicare and reform government program reimbursement methodologies for pharmaceutical products.

Healthcare reform proposals recently culminated in the enactment of the Inflation Reduction Act (the “IRA”), in August 2022, which, among other things, will allow HHS to negotiate the selling price of certain drugs and biologics that CMS reimburses under Medicare Part B and Part D, although this will only apply to high-expenditure single-source drugs that have been approved for at least seven years (11 years for biologics).

The negotiated prices, which will first become effective in 2026, will be capped at a statutory ceiling price representing a significant discount from average prices to wholesalers and direct purchasers.

The law will also, beginning in October 2023, penalize drug manufacturers that increase prices of Medicare Part B and Part D drugs at a rate greater than the rate of inflation.

In addition, the law eliminates certain provisions under Medicare Part D beginning in 2025 by significantly lowering the beneficiary maximum out-of-pocket cost through a newly established manufacturer discount program.

The IRA also extends enhanced subsidies for individuals purchasing health insurance coverage in ACA marketplaces through plan year 2025.

The IRA permits the Secretary of HHS to implement many of these provisions through guidance, as opposed to regulation, for the initial years.

Manufacturers that fail to comply with the IRA may be subject to various penalties, including civil monetary penalties.

These provisions will take effect progressively starting in 2023, although they may be subject to legal challenges.

Thus, it is unclear how the IRA will be implemented but will likely have a significant impact on the pharmaceutical industry.

At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

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SAB Sciences, Inc.

(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 platform from Sanford Applied Biosciences, a wholly owned subsidiary of Sanford Health, to develop targeted human polyclonal antibodies 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 natural way our bodies fight disease through a human polyclonal antibody response.

(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 platform 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 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 polyclonal antibodies to multiple disease indications, and we have conducted or collaborated in eight clinical trials (six of which are ongoing or in review), where we have demonstrated safety and efficacy in multiple Tc Bovine-derived human polyclonal antibody product candidates.

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.

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.

Government emerging disease and medical countermeasures programs.

In October 2021 we completed our business combination with Big Cypress Acquisition Corp., pursuant to which we debuted as a publicly traded company (the "Business Combination").

Big Cypress Acquisition Corp.

("BCYP") was incorporated as a special purpose acquisition company in the State of Delaware on November 12, 2020.

In October 2021 we completed our business combination with Big Cypress Acquisition Corp.

("BCYP"), pursuant to which we debuted as a publicly traded company (the "Business Combination").

BCYP was incorporated as a special purpose acquisition company in the State of Delaware on November 12, 2020.

On January 14, 2021, BCYP completed its initial public offering.

On October 22, 2021, BCYP consummated the Business Combination with Legacy SAB, which changed its name from SAB Biotherapeutics, Inc.

to SAB Sciences, Inc.

In connection with the closing of the Business Combination, BCYP changed its name to SAB Biotherapeutics, Inc.

and SAB Sciences, Inc.

became a subsidiary of SAB Biotherapeutics, Inc.

to Legacy SAB. In connection with the closing of the Business Combination, BCYP changed its name to SAB Biotherapeutics, Inc.

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.

Our corporate website address is www.sabbiotherapeutics.com.

Information contained on or accessible through our website is not a part of this Form 10-K, and the inclusion of our website address herein is an inactive textual reference only.

Our corporate website address is www.sab.bio. Our Annual Reports on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K and proxy statements, and all amendments thereto, are available free of charge on our website.

These reports are posted on our website as soon as reasonably practicable after they are electronically filed with the SEC.

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.

Human Capital

As of December 31, 2021, we had 139 full-time employees, including 14 who hold advanced degrees.

Of these employees, 115 were engaged in research and development activities, 6 were engaged in clinical activities and 18 were engaged in general and administrative activities.

As of December 31, 2021, none of our employees are represented by labor unions or covered by collective bargaining agreements.

As of December 31, 2022, we had 56 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, 2022, none of our employees were represented by labor unions or covered by collective bargaining agreements.

We consider our relationship with our employees to be good.

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What changed 10-K

Item 1. Business