Serum Sickness

First subject has been dosed in the first-in-man Phase 1 clinical study of SAB-142, the first fully-human anti-thymocyte immunoglobulin (ATG) SAB-142 directly and specifically targets multiple immune cells involved in the destruction of insulin-producing pancreatic beta cells to potentially preserve beta cell function SAB Biotherapeutics is pursuing IND and CTA filings with U.S. FDA and EMA in 2024 to clinically advance development of SAB-142 into Phase 2b study SAB Biotherapeutics, Inc. (Nasdaq: SABS), a clinical-stage biopharmaceutical company with a novel immunotherapy platform that is developing fully-human anti-thymocyte immunoglobulin (hIgG) for disease-modification of Type 1 Diabetes (T1D) through delaying the onset and/or progression of the disease, today announced that the first participants of a HUMAN trial (Fully HUman anti-thymocyte biologic in first-in-MAN clinical study) have been dosed in Australia. This Phase 1 randomized, double-blind, placebo-controlled, single-ascending dose, adaptive design clinical study was designed to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of intravenous SAB-142 in healthy volunteers and participants with T1D. SAB-142 is a first-in-class fully-human anti-thymocyte immunoglobulin being developed as a disease-modifying treatment to delay the onset and progression of T1D. In October 2023, SAB received approval by the Australian Human Research Ethics Committee (HREC) to commence the Phase 1 clinical trial investigating safety, tolerability, pharmacokinetic, pharmacodynamic, and immunogenicity of SAB-142. The primary objective of the trial is two-fold: 1) to generate data on differentiated safety and immunogenicity of this fully-human immunoglobulin, and 2) to establish a Proof of Biological Activity (POBA) for SAB-142. Establishing POBA will focus on validating the immunological effects associated with an anti-thymoglobulin mechanism of action in modulating autoimmune response associated with progression of T1D. Those immunological effects have been previously elucidated in efficacy trials in T1D patients with rabbit-derived anti-thymocyte globulin (ATG). More information about the Phase 1 clinical trial with SAB-142 (ACTRN:12623001089628) can be found here. “This marks an important milestone in our development of SAB-142 as our lead asset enters the clinic,” said Alexandra Kropotova, MD, MBA, Executive Vice President and Chief Medical Officer of SAB. “We believe SAB-142 has the potential to be a best-in-class treatment for disease-modification through safe and precise immunomodulation in T1D, based on its validated mechanism of action and safety advantages over rabbit-derived ATG, which has shown significant promise in T1D disease modification. I would also like to extend gratitude on behalf of the entire SAB team to the trial participants and to our Phase 1 partners Avance and Nucleus Network, without whom this trial wouldn’t be possible.” The program is expected to rapidly expand globally, subject to regulatory approvals in the United States, United Kingdom and European Union countries. SAB is on track to file an Investigational New Drug (IND) application for SAB-142 with the U.S. Food and Drug Administration (FDA) in 2024, along with filings in UK and EU countries to enable efficient progress towards the Phase 2b development. “For people living with T1D, the burden of disease is significant and there’s increasing focus – and need – within the research community to focus on disease-modification, a departure from the focus on symptom management that has long been the norm,” said Dr. Kristi McLendon, principal investigator at the Nucleus Network, who is leading the Phase 1 trial. “We are grateful to partner with SAB on this Phase 1 investigation that will explore the therapeutic potential of a new, potentially best-in-class immunotherapeutic option for patients.” SAB-142 is a fully-human alternative to rabbit anti-thymocyte globulin (ATG). SAB-142’s mechanism of action is similar to that of rabbit ATG, which has been clinically validated in multiple clinical trials for type 1 diabetes, demonstrating the ability to slow down disease progression in patients with new or recent onset of Stage 3 type 1 diabetes. Two clinical trials have shown that a single, low dose of rabbit ATG has demonstrated the ability to modulate the body’s immune response to help slow beta cell destruction and preserve the ability of these cells to generate insulin, which the body needs to regulate blood sugar and carry out all human activities. SAB-142, like rabbit ATG, directly targets multiple immune cells involved in destroying pancreatic beta cells. By stopping immune cells from attacking beta cells, this treatment has potential to preserve insulin-producing beta cells. However, most humans treated with rabbit ATG develop serum sickness and anti-drug antibodies from exposure to the rabbit-derived antibody. SAB-142 is a human antibody, intended to allow safe, consistent re-dosing for type 1 diabetes, a lifelong chronic disease, without the potential risk of inducing the major adverse immune reactions that can occur with administration of a fully animal ATG. SAB Biotherapeutics (SAB) is a clinical-stage biopharmaceutical company focused on developing fully human, multi-targeted, high-potency immunoglobulins (IgGs), without the need for human donors or convalescent plasma, to treat and prevent immune and autoimmune disorders. The company’s lead asset, SAB-142, targets type 1 diabetes (T1D) with a disease-modifying therapeutic approach that aims to change the treatment paradigm by delaying onset and potentially preventing disease progression. Using advanced genetic engineering and antibody science to develop Transchromosomic (Tc) Bovine™, the only transgenic animal with a human artificial chromosome, SAB’s DiversitAb™ drug development production system is able to generate a diverse repertoire of specifically targeted, high-potency, fully-human IgGs that can address a wide range of serious unmet needs in human diseases without the need for convalescent plasma or human donors. For more information on SAB, visit: https://www.SAb.bio/. The content above comes from the network. if any infringement, please contact us to modify.

Funding will support development of SAB-142, a potential disease-modifying therapy for type 1 diabetes and other autoimmune conditionsParticipating investors include Sessa Capital, BVF Partners, RTW Investments, Marshall Wace, ATW, and the JDRF T1D FundFunds are expected to sustain development of SAB-142 through Phase 1 trial SIOUX FALLS, S.D., Nov. 14, 2023 (GLOBE NEWSWIRE) -- SAB Biotherapeutics, Inc. (NASDAQ: SABS), a clinical stage biopharmaceutical company with a novel immunotherapy platform that is developing fully-human anti-thymocyte immunoglobulin (hIgG) for delaying the onset of progression of type 1 diabetes (T1D), today announced the funding of the second tranche of a previously-announced financing, raising total aggregate proceeds to date of $67.1 million. The proceeds from the financing will be used to fund the development of the company’s lead research program, SAB-142, a potential disease modifying treatment for T1D. Tranche B warrants remain outstanding, which if exercised, would result in a total of $110 million in proceeds in this financing. Participating investors included Sessa Capital, BVF Partners, RTW Investments, Marshall Wace, ATW, and the JDRF T1D Fund. The investment will move human trials forward for SAB’s lead research program, which was recently granted approval by Australian authorities to begin a first-in-human Phase 1 clinical study of SAB-142, the first fully-human anti-thymocyte immunoglobulin (ATG), with plans to pursue an investigational new drug application with the U.S. Food and Drug Administration (FDA). SAB-142 directly targets multiple immune cells involved in destroying insulin-producing pancreatic beta cells to potentially preserve beta cell function. “Patients and their families are long overdue for potentially disease-modifying treatments, which are at the forefront of innovation for the 1.6 million Americans living daily with this disease,” said Eddie J. Sullivan, Ph.D., Co-Founder, President, and Chief Executive Officer of SAB Biotherapeutics. “The partnership and continued confidence of our investors will allow us to advance clinical trials of SAB-142, as we work to address the root cause of T1D. The closure of this tranche is an important step forward to advance a new clinical approach in T1D.” Samuel J. Reich, Executive Chairman of SAB, said “Investors are recognizing that type 1 diabetes is a critical therapeutic area within the biopharmaceutical industry, as disease modification offers a necessary and improved treatment path for millions of patients who manage this disease on a daily basis. We are grateful for the dedication of our investors that have been fully immersed in the due diligence process for SAB-142 over the course of many months and their unwavering confidence in SAB to develop a superior disease-modifying approach for patients living with type 1 diabetes. We look forward to continuing our partnership with this world-class syndicate of investors to bring our important mission to reality.” Chardan served as the exclusive placement agent for the private placement transaction. Raymond James acted as financial advisor. Brookline Capital Markets, a division of Arcadia Securities, LLC, also acted as financial advisor. Milestone Advisors acted as strategic advisor. About SAB-142 SAB-142 is a fully-human alternative to rabbit anti-thymocyte globulin (ATG). SAB-142’s mechanism of action is similar to that of rabbit ATG, which has been clinically validated in multiple clinical trials for type 1 diabetes, demonstrating the ability to slow down disease progression in patients with new or recent onset of Stage 3 type 1 diabetes. Two clinical trials have shown that a single, low dose of rabbit ATG has demonstrated the ability to modulate the body’s immune response to help slow beta cell destruction and preserve the ability of these cells to generate insulin, which the body needs to regulate blood sugar and carry out all human activities. SAB-142, like rabbit ATG, directly targets multiple immune cells involved in destroying pancreatic beta cells. By stopping immune cells from attacking beta cells, this treatment has potential to preserve insulin-producing beta cells. However, most humans treated with rabbit ATG develop serum sickness and anti-drug antibodies from exposure to the rabbit-derived antibody. SAB-142 is a human antibody, intended to allow safe, consistent re-dosing for type 1 diabetes, a lifelong chronic disease, without the potential risk of inducing the major adverse immune reactions that can occur with administration of a fully animal ATG. About SAB Biotherapeutics, Inc.SAB Biotherapeutics (SAB) is a clinical-stage biopharmaceutical company focused on developing fully human, multi-targeted, high-potency immunoglobulins (IgGs), without the need for human donors or convalescent plasma, to treat and prevent immune and autoimmune disorders. The company’s lead asset, SAB-142, targets type 1 diabetes (T1D) with a disease-modifying therapeutic approach that aims to change the treatment paradigm by delaying onset and potentially preventing disease progression. Using advanced genetic engineering and antibody science to develop Transchromosomic (Tc) Bovine™, the only transgenic animal with a human artificial chromosome, SAB’s DiversitAb™ drug development production system is able to generate a diverse repertoire of specifically targeted, high-potency, fully-human IgGs that can address a wide range of serious unmet needs in human diseases without the need for convalescent plasma or human donors. For more information on SAB, visit: https://www.SAb.bio/ and follow SAB on Twitter and LinkedIn. Forward-Looking StatementsCertain statements made herein that are not historical facts are forward-looking statements for purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Forward-looking statements generally are accompanied by words such as “believe,” “may,” “will,” “to be,” “estimate,” “continue,” “anticipate,” “intend,” “expect,” “should,” “would,” “plan,” “predict,” “potential,” “seem,” “seek,” “future,” “outlook,” and similar expressions that predict or indicate future events or trends or that are not statements of historical matters. These forward-looking statements include, but are not limited to, statements regarding future events, including the development and efficacy of our T1D program, and other discovery programs, the closing of each tranche of the Company’s private placement offering, the timely funding to the Company by each investor in the private placement offering, financial projections and future financial and operating results (including estimated cost savings and cash runway), the outcome of and potential future government, and other third-party collaborations or funded programs. These statements are based on the current expectations of SAB and are not predictions of actual performance, and are not intended to serve as, and must not be relied on, by any investor as a guarantee, prediction, definitive statement, or an assurance, of fact or probability. These statements are only current predictions or expectations, and are subject to known and unknown risks, uncertainties and other factors which may be beyond our control. Actual events and circumstances are difficult or impossible to predict, and these risks and uncertainties may cause our or our industry’s results, performance, or achievements to be materially different from those anticipated by these forward-looking statements. A further description of risks and uncertainties can be found in the sections captioned “Risk Factors” in our most recent annual report on Form 10-K, as amended, subsequent quarterly reports on Form 10-Q, as may be amended or supplemented from time to time, and other filings with or submissions to, the U.S. Securities and Exchange Commission, which are available at https://www.sec.gov/. Except as otherwise required by law, SAB disclaims any intention or obligation to update or revise any forward-looking statements, which speak only as of the date they were made, whether as a result of new information, future events, or circumstances or otherwise. CONTACTS Investor Relations:Matt@milestone-advisorsllc.com Media Relations:SABPR@westwicke.com

LIKMEZ™ (metronidazole) Oral Suspension, the First and Only FDA-Approved Liquid Option for Patients with Adherence Hurdles such as Dysphagia, Difficulty Swallowing Kesin Pharma Launches Novel Formulation of Mainstay Anti-Infective, Metronidazole Kesin Pharma: Solutions for Better Health™ OLDSMAR, Fla.--(BUSINESS WIRE)-- Kesin Pharma Corporation, a pharmaceutical company focused on innovative Specialty brands and Unit Dose formulations, announced today that the U.S. Food and Drug Administration (FDA) has approved LIKMEZ™ (metronidazole) oral suspension, 500 mg/5 mL. Available now, LIKMEZ™ is the first and only FDA-approved ready-to-use oral liquid metronidazole in the U.S. market. LIKMEZ™ is a novel presentation of a mainstay antibiotic drug, reinvented to address common adherence issues. Kesin is the exclusive U.S. commercialization partner for LIKMEZ™ through its collaboration with Saptalis Pharmaceuticals, LLC, the developer and NDA holder of the product. LIKMEZ™ is a novel proprietary liquid formulation of metronidazole for patients who may struggle with dysphagia, difficulty swallowing, or high taste sensitivities. These potential compliance and persistency obstacles can lead to treatment discontinuation and inefficient treatment outcomes, including rebound infection. LIKMEZ™ is approved for the treatment of trichomoniasis and anaerobic bacterial infections in adults and amebiasis in adults and pediatric patients. LIKMEZ™ comes in a 200 mL bottle as a strawberry peppermint flavored suspension, with a 24-month shelf life and does not require refrigeration. Metronidazole has been shown to be carcinogenic in mice and rats, and the most common adverse reactions to metronidazole include nausea, headache, anorexia, vomiting, diarrhea, abdominal cramping, epigastric distress, and constipation. LIKMEZ™ addresses inherent risks associated with crushing tablets for those patients needing a liquid formulation and eliminates the potential inconsistences associated with extemporaneously compounding metronidazole prescriptions. Additionally, compounding can amplify the pronounced bitter, metallic taste of metronidazole tablets, which can also negatively influence patients’ adherence to therapy. “LIKMEZ™ is for patients and providers who need a liquid option for those faced with adherence obstacles due to taste sensitivities or difficulty swallowing. An increasing number of patients can benefit from a safe and efficacious product that can support medication adherence. We are very excited with our first brand launch which is part of our upcoming pipeline of novel products, designed to address unmet patient needs and bring value to the healthcare system,” said Narasimhan Mani, President & CEO of Kesin Pharma Corporation. “We are pleased with our partnership with Saptalis Pharmaceuticals, the NDA holder and manufacturer of LIKMEZ™. The timely approval of this NDA505(b)(2) presents a significant opportunity for Kesin Pharma to bring a value-added product to the market,” said Narasimhan Mani. LIKMEZ™ will be available through most full-line wholesalers and retail pharmacies. To learn more and view Full Prescribing Information, including complete BOXED WARNING and additional Safety Information see . About Kesin Pharma Kesin Pharma Corporation, based in Oldsmar, FL, is a specialty pharmaceutical company with deep experience and strong capabilities in commercial sales & marketing, distribution, and market access. Kesin’s mission is to provide unique healthcare solutions to patients through our portfolio of strategic, value-driven brand and unit-dose products. Kesin Pharma works closely with patients, payers, and provider partners to bring to market innovative pharmaceutical products to better address unfulfilled needs and enhance patient adherence and accessibility. For more information, visit . About Saptalis Pharmaceuticals, LLC Saptalis Pharmaceuticals, LLC is a rapidly growing pharmaceutical company specialized in development, manufacturing, and commercialization of generic and innovative products in liquid and semi-solid dosage forms. Located in the Hauppauge Industrial Park on Long Island, NY, USA, Saptalis has fully equipped Research & Development Laboratories and state of the art commercial scale manufacturing facility designed to meet FDA cGMP requirements. For more information, visit . Important Safety Information INDICATIONS AND USAGE LIKMEZ™ (metronidazole) is a nitroimidazole antimicrobial indicated for: Trichomoniasis in adults Amebiasis in adults and pediatric patients Anaerobic Bacterial Infections in adults To reduce the development of drug-resistant bacteria and maintain the effectiveness of LIKMEZ™ and other antibacterial drugs, LIKMEZ™ should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. WARNING: POTENTIAL FOR CARCINOGENICITY Metronidazole has been shown to be carcinogenic in mice and rats. Avoid unnecessary use of LIKMEZ™. Reserve LIKMEZ™ for use in the following indications: trichomoniasis, amebiasis, and anaerobic bacterial infections. See full prescribing information for complete BOXED WARNING. CONTRAINDICATIONS Hypersensitivity Reactions: LIKMEZ is contraindicated in patients with known hypersensitivity to metronidazole or other nitroimidazole derivatives. Psychotic Reactions with Disulfiram: LIKMEZ is contraindicated in patients who have used disulfiram within the last two weeks. Use of oral metronidazole is associated with psychotic reactions in alcoholic patients who were using disulfiram concurrently. Interaction with Alcohol: LIKMEZ is contraindicated in patients who consume alcohol or products containing propylene glycol during and for at least three days after LIKMEZ therapy. Use of oral metronidazole is associated with a disulfiram-like reaction to alcohol, including abdominal cramps, nausea, vomiting, headaches, and flushing. Cockayne Syndrome: LIKMEZ is contraindicated in patients with Cockayne syndrome. WARNINGS AND PRECAUTIONS Potential for Carcinogenicity: Metronidazole has been shown to be carcinogenic in mice and rats. Reserve LIKMEZ for use in the following indications: trichomoniasis, amebiasis, and anaerobic bacterial infections. Central and Peripheral Nervous System Effects: Encephalopathy, aseptic meningitis, peripheral neuropathy (including optic neuropathy) and convulsive seizures have been reported with metronidazole. The appearance of abnormal neurological signs and symptoms demands the prompt evaluation of the benefit/risk ratio of the continuation of therapy. Fungal Superinfections: Known or previously unrecognized candidiasis may present more prominent symptoms during therapy with LIKMEZ and requires treatment with an antifungal agent. Blood Dyscrasias: LIKMEZ is a nitroimidazole and should be used with care in patients with evidence of or history of blood dyscrasia. Total and differential leukocyte counts are recommended before and after therapy. Drug-Resistant Bacteria: Prescribing LIKMEZ in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Adverse Reactions The most serious adverse reactions in patients treated with metronidazole have been convulsive seizures, encephalopathy, aseptic meningitis, optic and peripheral neuropathy, the latter characterized mainly by numbness or paresthesia of an extremity. Persistent peripheral neuropathy has been reported in some patients receiving prolonged administration of metronidazole. In addition, headache, syncope, dizziness, vertigo, incoordination, ataxia, confusion, dysarthria, irritability, depression, weakness, and insomnia have been reported. The most common adverse reactions reported: Gastrointestinal: The most common adverse reactions reported have been referable to the gastrointestinal tract, particularly nausea, sometimes accompanied by headache, anorexia, and occasionally vomiting; diarrhea; epigastric distress; and abdominal cramping and constipation. Mouth: A sharp, unpleasant metallic taste is not unusual. Furry tongue, glossitis, and stomatitis have occurred; these may be associated with a sudden overgrowth of Candida which may occur during therapy. Dermatologic: Erythematous rash and pruritus. Hematopoietic: Reversible neutropenia (leukopenia); reversible thrombocytopenia. Cardiovascular: QT prolongation has been reported, particularly when metronidazole was administered with drugs with the potential for prolonging the QT interval. Flattening of the T‑wave may be seen in electrocardiographic tracings. Hypersensitivity: Urticaria, erythematous rash, Stevens-Johnson Syndrome, toxic epidermal necrolysis, flushing, nasal congestion, dryness of the mouth (or vagina or vulva), and fever. Renal: Dysuria, cystitis, polyuria, incontinence, and a sense of pelvic pressure. Instances of darkened urine have been reported by approximately one patient in 100,000. Although the pigment which is probably responsible for this phenomenon has not been positively identified, it is almost certainly a metabolite of metronidazole and seems to have no clinical significance. Other: Proliferation of Candida in the vagina, dyspareunia, decrease of libido, proctitis, and fleeting joint pains sometimes resembling “serum sickness”. Cases of pancreatitis, which generally abated on withdrawal of the drug, have been reported. Patients with Crohn’s disease are known to have an increased incidence of gastrointestinal and certain extraintestinal cancers. There have been some reports in the medical literature of breast and colon cancer in Crohn’s disease patients who have been treated with metronidazole at high doses for extended periods of time. A cause-and-effect relationship has not been established. Crohn’s disease is not an approved indication for LIKMEZ. DRUG INTERACTIONS Disulfiram: Psychotic reactions have been reported in alcoholic patients who are using metronidazole and disulfiram concurrently. LIKMEZ is contraindicated in patients who have taken disulfiram within the last two weeks. Alcoholic Beverages: LIKMEZ is contraindicated in patients who consume alcohol or products containing propylene glycol during and for at least 3 days after therapy with LIKMEZ. Use of LIKMEZ with alcohol or other products containing propylene glycol is associated with a disulfiram-like reaction (abdominal cramps, nausea, vomiting, headaches, and flushing) Warfarin and other Oral Anticoagulants: Metronidazole has been reported to potentiate the anticoagulant effect of warfarin and other oral coumarin anticoagulants, resulting in a prolongation of prothrombin time. When LIKMEZ is prescribed for patients on this type of anticoagulant therapy, prothrombin time and INR should be carefully monitored. Lithium: In patients stabilized on relatively high doses of lithium, short-term use of LIKMEZ has been associated with elevation of serum lithium concentrations and signs of lithium toxicity due to the interaction between metronidazole and lithium. Monitor serum lithium and serum creatinine concentrations for several days after beginning treatment with LIKMEZ to detect any increase that may precede clinical symptoms of lithium toxicity. Busulfan: Metronidazole has been reported to increase plasma concentrations of busulfan, which can result in an increased risk for serious busulfan toxicity. Do not administer LIKMEZ concomitantly with busulfan unless the benefit outweighs the risk. Inhibitors of CYP450 Liver Enzymes: The simultaneous administration of LIKMEZ and drugs that decrease microsomal liver enzymes, such as cimetidine, may prolong the half-life and decrease plasma clearance of metronidazole. Inducers of CYP450 Liver Enzymes: The simultaneous administration of LIKMEZ and drugs that induce microsomal liver enzymes, such as phenytoin or phenobarbital, may accelerate the elimination of metronidazole, resulting in reduced plasma concentrations of metronidazole. Impaired clearance of phenytoin has also been reported. Drugs that Prolong the QT Interval: QT prolongation has been reported. Drug/Laboratory Test Interactions: Metronidazole may interfere with certain types of determinations of serum chemistry values. Values of zero may be observed. USE IN SPECIFIC POPULATIONS Pregnancy Risk Summary: Most studies did not show an increased risk for congenital anomalies or other adverse fetal outcomes following metronidazole exposure during pregnancy. Lactation Risk Summary: There are no data on the effects of metronidazole on milk production. Pediatric Use: The safety and effectiveness of LIKMEZ for the treatment of amebiasis have been established in pediatric patients. The safety and effectiveness of LIKMEZ for the treatment of trichomoniasis and anaerobic bacterial infections have not been established in pediatric patients. Geriatric Use: In elderly geriatric patients, monitoring for LIKMEZ associated adverse events is recommended. Decreased liver function in geriatric patients can result in increased concentrations of metronidazole that may necessitate adjustment of metronidazole dosage. Renal Impairment: Patients with end-stage renal disease may excrete metronidazole and metabolites slowly in the urine, resulting in significant accumulation of metronidazole metabolites. Monitoring for LIKMEZ associated adverse events is recommended. Hepatic Impairment: Patients with hepatic impairment metabolize metronidazole slowly, with resultant accumulation of metronidazole in the plasma. For patients with severe hepatic impairment, reduce the dose of LIKMEZ by 50%. For patients with mild to moderate hepatic impairment, no dosage adjustment is needed but these patients should be monitored for LIKMEZ associated adverse reactions. OVERDOSAGE There is no specific antidote for metronidazole overdose; therefore, management of the patient should consist of symptomatic and supportive therapy. In case of an overdose, patients should contact a physician, poison control center, or emergency room. Please see full Prescribing Information, including BOXED WARNING at LIKMEZ™ and the stylized LIKMEZ™ logo are registered trademarks of Saptalis Pharmaceuticals, LLC. LIKMEZ™ is marketed by Kesin Pharma Corporation. © 2023 Kesin Pharma Corporation. All rights reserved.