TLR2

The porous material, derived from shellfish, optimizes absorption while activating a previously overlooked blood-clotting mechanism, stemming bleeding within minutes. More than 11 million people in the United States take anticoagulation or antiplatelet medications, such as heparin or aspirin, to treat serious conditions like heart attack and stroke. However, these medications also put patients at risk of life-threatening bleeding in the case of injury or during surgery. To improve strategies for reducing blood loss, a team led by investigators from Brigham and Women's Hospital, a founding member of the Mass General Brigham healthcare system, developed a porous material that maximizes blood absorption and effectively activates clotting mechanisms, even in patients on anticoagulation or antiplatelet medication. Findings, published in PNAS, show that the bleed-stopping material, or "hemostat," halted bleeding within an average of about five minutes in patients on anticoagulants who underwent cardiac catheterization, a dramatic reduction from traditional compression methods that can take over two hours. "This is a next-generation hemostat that effectively stops bleeding, even in patients who take anticoagulation or antiplatelet medications," said corresponding author Hae Lin Jang, Ph.D., of the Center for Engineered Therapeutics. "We used an exciting, interdisciplinary approach that combines engineering principles, materials science, and understandings of molecular biology to overcome the limitations of existing therapies and address a real clinical need." Over 5 million people globally die each year due to trauma, with over a third of these deaths attributed to uncontrolled bleeding. The researchers used what is known as a "rational engineering" approach to develop a more effective hemostat. They began by simulating blood flow through pores to determine what microscopic design would optimize absorption. They drew inspiration from the architecture of the human lungs, which contain spherical "air sacs" called alveoli that enable a high interaction rate with blood within a short time. Alveoli have a large surface area based on their tortuous porous structure, which led the researchers to engineer a highly interconnected, spherical microporous structure in their material to rapidly absorb blood and accumulate clotting components like platelets in a highly concentrated manner, which facilitate blood clotting. The researchers developed the alveoli-like structure using chitosan, which can be extracted from shellfish. Chitosan is already used in some hemostats: its positively charged surface is known to strongly attract negatively charged platelets and fibrinogen, the two major components of a blood clot. However, contrary to previous assumptions, the researchers discovered that chitosan also directly stimulates blood clotting by activating the TLR-2 clotting pathway, making it a viable mechanism for increasing blood clotting even in patients on anticoagulants. The researchers demonstrated the efficacy of the material in 70 patients who underwent cardiovascular catheterization procedures while on the anticoagulant heparin, with bleeding observed to stop after a mean time of about five minutes for patients on low-dose heparin and in under about nine minutes in patients on heparin doses of up to 12,500 IU. Other advantages of the hemostatic material included its easy application and removal. The chitosan pad eliminated the need for strong and prolonged compression, which can take several hours and requires extensive nursing. Furthermore, gauze removal can cause severe pain to patients and is frequently associated with a reoccurrence of bleeding; in contrast, the more absorptive chitosan hemostat was removed relatively cleanly from wounds and received high patient comfort scores. The researchers are continuing to study the wound-healing process after application of the chitosan hemostat. Moreover, they are investigating other next-generation wound dressings, which may be able to deliver drugs or improve the cleanliness of the wound environment, thus reducing the need for frequent changes. "This hemostat can save valuable time in emergency situations," said first author Vivian K. Lee, Ph.D., of the Center for Engineered Therapeutics. "In emergencies, it can be extremely challenging to screen the prescription information of a patient to provide appropriate anticoagulation reversal therapy to patients on anticoagulants. If a hemostat can bypass a medication's anticoagulating mechanisms, it can be used in a wide range of patients, saving time, and potentially saving lives."

-- New $3.8 million DOD contract extension will fund non-clinical safety studies to support a three-month seasonal prophylaxis Phase 2b study in at-risk populations, comprising elderly individuals with comorbidities, including chronic lung diseases and diabetes. -- ENA Respiratory names new clinical leaders and consultants to accelerate and optimize its research and development program. SYDNEY, Australia, Aug. 29, 2023 (GLOBE NEWSWIRE) -- Clinical-stage pharmaceutical company ENA Respiratory has been awarded an additional $3.8 million contract from the U.S. Department of Defense (DOD) to support ongoing research and development of INNA-051, a first-in-class, intranasal, innate immune modulator for the prevention of complications associated with respiratory viral infections in at-risk populations. The company also announced new clinical leadership and consultants as it plans for a seasonal prophylaxis Phase 2b study. The new funding adds to the $4.38 million initial DOD funding the company announced in January 2023, which has been used to implement INNA-051 manufacturing on a larger scale. The funds also supported the development of a dry powder formulation that is expected to provide long-term stability of at least 24 months at room temperature. The new funding will support the non-clinical toxicology and safety studies needed to enable a seasonal prophylaxis Phase 2b study to demonstrate the safety, tolerability, and efficacy of intranasal INNA-051 in preventing respiratory illness in people aged 65 or older. “Early studies validated the safety of INNA-051 and provided proof of pharmacology by accelerating virus clearance and boosting host defense responses against common respiratory viruses,” said Christophe Demaison, Ph.D., co-founder and CEO of ENA Respiratory. “We are grateful for the U.S. DOD support and look forward to continuing to study INNA-051 in preventing respiratory illnesses, especially in those at greatest risk of exposure, complications, or hospitalization.” The contract was awarded by the DOD’s Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND), Joint Project Manager for Chemical, Biological, Radiological, and Nuclear Medical in collaboration with the Defense Innovation Unit (DIU). ENA Respiratory Names Expanded Clinical Leadership The company also announced new leadership and consultants to accelerate and optimize its research and development program. Ruth Tal-Singer, Ph.D., joins as Medicine Development Leader to oversee all clinical development efforts. Previously, Dr. Tal-Singer was a Consultant and Board Member for ENA Respiratory. She is an internationally recognized scientist with extensive experience in molecular biology, immunology, and application of digital technology and in vivo disease models in clinical development. Most recently, she served as President and CEO of the COPD Foundation, where she launched the Foundation’s digital health, medical devices, and therapeutics development accelerator network, COPD360Net®, and championed its partnership with ENA Respiratory. Her efforts to ensure the patient voice is central to lung disease therapeutics development continue in her volunteer role as Chief Scientific Officer of the Global Allergy and Airways Patient Platform (GAAPP). Earlier in her career, she served in senior leadership roles at GSK R&D. Courtney Crim, M.D., joins as Clinical Consultant and acting Chief Medical Officer. He also serves as Clinical Associate Professor of Medicine in the Division of Pulmonary and Critical Care Medicine at the University of North Carolina in Chapel Hill. Previously, he was Group Director in Clinical Development in Respiratory Clinical Sciences at GSK, designing Phase 2-4 clinical trials. He has also served on the FDA Pulmonary and Allergy Drug Advisory Committee and presented drug approval submissions to U.S., European, and other regulatory agencies. Bruce Miller, Ph.D., joins as a Clinical Consultant with more than 30 years of experience developing therapies for COPD and other inflammatory-driven diseases. He has previously served in senior scientific roles at GSK, Johnson & Johnson, Rhone-Poulenc Rorer, and Sterling Winthrop Pharmaceuticals. Active in the industry, he previously served as co-chair of the COPD Foundation’s COPD Biomarker Qualification Consortium’s Fibrinogen Working Group, which was instrumental in gaining regulatory qualification for a biomarker as a drug development tool in COPD trials. “Our accomplished team brings decades of experience leading clinical research programs for respiratory diseases and successfully submitting new therapies for regulatory approvals in the U.S., Europe, and other regions,” said Dr. Demaison. “With these additions to our team, we are well-positioned to continue the clinical development of INNA-051 in the context of natural respiratory tract infections in individuals with increased risk of severe illness or exposure.” Effort sponsored by the U.S. Government under Other Transaction number HQ0845-23-9-0003 between ENA Respiratory Pty Ltd and the U.S. Government. The U.S. Government is authorized to reproduce and distribute reprints for Governmental purposes, notwithstanding any copyright notation thereon. The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies or endorsements, either expressed or implied, of the U.S. Government. Notes to Editors If you would like to arrange an interview, please contact: Glenn Silver, FINN Partners, +1 973 818 8198, glenn.silver@finnpartners.com About ENA Respiratory ENA Respiratory is aiming to transform the prevention of complications associated with respiratory viral infections in populations at-risk of complications. The company is based in Melbourne and Sydney, Australia, and it has secured a Series A investment from Brandon Capital Partners’ managed funds, the Minderoo Foundation, and Uniseed. In 2022, ENA Respiratory partnered with the US-based COPD Foundation to accelerate the clinical development of INNA-051 in COPD through its access to patients, a global network of accredited centres, scientific expertise, and patient investigators. That year, the company was also the first in the Asia Pacific region to be selected to join BLUE KNIGHT™, a joint initiative between Johnson & Johnson Innovation and U.S. BARDA. In 2023, the company was additionally awarded a USD $4.38 million contract from the U.S. Department of Defense to support ongoing development of INNA-051. About INNA-051 INNA-051 is a potent innate immune TLR2/6 agonist. It is being developed for intranasal delivery to target the primary entry site of viral respiratory infections as most respiratory viruses, including SARS-CoV-2, Human Rhinovirus, RSV, and influenza, initially infect and replicate in nasal mucosa epithelial cells. By targeting protective host defense mechanisms that are virus agnostic and through its simple route of administration, INNA-051 has the potential to address a major unmet need in at-risk populations. It also has the potential to be rapidly deployed and complement vaccine and direct-acting antiviral efforts in the battle against current and future respiratory virus outbreaks, including COVID-19. In a Phase IIa influenza-challenge study, INNA-051 was found to accelerate virus clearance and boost host responses against influenza virus, including interferon responses. The human data confirmed pre-clinical data in human airway epithelial cells as well as rhinovirus, influenza, and COVID-19 animal infection models. INNA-051 is well-tolerated in humans at single and repeat doses. Key features of INNA-051 intranasal administration include minimal systemic bioavailability, durable immune response (supporting weekly administration), and compatibility with available vaccines and corticosteroids. Importantly, INNA-051 activity is not significantly affected by senescence (inflammaging), and its safety profile supports prophylaxis use. For more information, please visit https://enarespiratory.com

NEW YORK, April 19, 2023 (GLOBE NEWSWIRE) -- Indaptus Therapeutics, Inc. (Nasdaq: INDP, “Indaptus” or “the Company”), a biotechnology company focused on discovering and developing transformative therapeutics for patients, today announces data presented in a poster at the American Association for Cancer Research (AACR) annual scientific conference on the Company’s Decoy anti-tumor platform. The poster, titled, “A systemically administered killed bacteria-based multiple immune receptor agonist for pulsed anti-tumor immunotherapy,” authored by Michael J. Newman, Ph.D., the Company’s Founder and Chief Scientific Officer, was presented Tuesday, April 18, 2023. Highlights included: Decoy10 (a previous generation from the platform) is a novel, attenuated and stabilized multi-TLR, NLR and STING agonist bacteria-based immunotherapy that demonstrated 90% reduction of LPS-endotoxin activity and use of 100% killed, non-pathogenic bacteria Decoy10 inhibited tumor growth, metastasis, and induced tumor regressions as a single agent. Regressions were also seen with Decoy10 in combination with a non-steroidal anti-inflammatory drug (NSAID), an anti-PD-1 checkpoint inhibitor, low-dose chemotherapy (LDC), and LDC plus a targeted antibody. Regressions were durable and associated with immunological memory-mediated rejection of tumor rechallenge The data demonstrated that Decoy10 contains agonists of TLR2 (1/2 and 2/6), TLR4, TLR8, TLR9, NOD2 and STING, conferring the ability to activate both innate and adaptive immune pathways in tumors after a single safe i.v. dose of Decoy10 in combination with anti-PD-1 checkpoint therapy, an NSAID or both In vivo anti-tumor activity was seen with colorectal, breast, hepatocellular, pancreatic carcinomas, and non-Hodgkin’s lymphomas (mouse and human) in pre-clinical models Michael Newman, Ph.D., Indaptus’ Chief Scientific Officer and inventor of the Decoy platform, commented, “The data from this poster represent the culmination of the extensive pre-clinical work that we performed to bring us to our current position as a clinical-stage company. Importantly, our results demonstrate the potential for activity in multiple solid tumor indications with high unmet need and the flexibility to be combined with a wide variety of synergy partners. The Decoy platform appears to be unique in its ability to deliver a package of TLR2,4,8,9, NOD2 and STING agonists systemically in pre-clinical models, resulting in priming or activation of innate and adaptive immune pathways in tumors, particularly in the combination setting. We believe this represents a significant advance in the recruitment of the body’s own defenses in the fight against cancer, and we look forward to continuing to provide updates on both the INDP D-101 Phase 1 clinical trial and further research on the platform itself.” About the AACR Conference 2023 The AACR Annual Meeting is the focal point of the cancer research community, where scientists, clinicians, other health care professionals, survivors, patients, and advocates gather to share the latest advances in cancer science and medicine. From population science and prevention; to cancer biology, translational, and clinical studies; to survivorship and advocacy; the AACR Annual Meeting highlights the work of the best minds in cancer research from institutions all over the world. About Indaptus Therapeutics Indaptus Therapeutics has evolved from more than a century of immunotherapy advances. The Company’s novel approach is based on the hypothesis that efficient activation of both innate and adaptive immune cells and pathways and associated anti-tumor and anti-viral immune responses will require a multi-targeted package of immune system-activating signals that can be administered safely intravenously (i.v.). Indaptus’ patented technology is composed of single strains of attenuated and killed, non-pathogenic, Gram-negative bacteria producing a multiple Toll-like receptor (TLR) agonist Decoy platform. The products are designed to have reduced i.v. toxicity, but largely uncompromised ability to prime or activate many of the cells and pathways of innate and adaptive immunity. Decoy products represent an antigen-agnostic technology that have produced single-agent activity against metastatic pancreatic and orthotopic colorectal carcinomas, single agent eradication of established antigen-expressing breast carcinoma, as well as combination-mediated eradication of established hepatocellular carcinomas and non-Hodgkin’s lymphomas in standard pre-clinical models, including syngeneic mouse tumors and human tumor xenografts. In pre-clinical studies tumor eradication was observed with Decoy products in combination with anti-PD-1 checkpoint therapy, low-dose chemotherapy, a non-steroidal anti-inflammatory drug, or an approved, targeted antibody. Combination-based tumor eradication in pre-clinical models produced innate and adaptive immunological memory, involved activation of both innate and adaptive immune cells, and was associated with induction of innate and adaptive immune pathways in tumors after only one i.v. dose of Decoy product, with associated “cold” to “hot” tumor inflammation signature transition. IND-enabling, nonclinical toxicology studies demonstrated safe i.v. administration without sustained induction of hallmark biomarkers of cytokine release syndromes, possibly due to passive targeting to liver, spleen, and tumor, followed by rapid elimination of the product. Indaptus’ Decoy products have also produced significant single agent activity against chronic hepatitis B virus (HBV) and chronic human immunodeficiency virus (HIV) infections in pre-clinical models. Forward-Looking Statements This press release contains forward-looking statements with the meaning of the Private Securities Litigation Reform Act. These include statements regarding management’s expectations, beliefs and intentions regarding, among other things, our expectations and plans regarding the Phase 1 clinical trial of Decoy20, including the timing and design thereof; the plans and objectives of management for future operations; our research and development activities; and our beliefs regarding the efficacy of our product candidates and the Decoy platform. Forward-looking statements can be identified by the use of forward-looking words such as “believe”, “expect”, “intend”, “plan”, “may”, “should”, “could”, “might”, “seek”, “target”, “will”, “project”, “forecast”, “continue” or “anticipate” or their negatives or variations of these words or other comparable words or by the fact that these statements do not relate strictly to historical matters. Because forward-looking statements relate to matters that have not yet occurred, these statements are inherently subject to risks and uncertainties that could cause our actual results to differ materially from any future results expressed or implied by the forward-looking statements. Many factors could cause actual activities or results to differ materially from the activities and results anticipated in forward-looking statements, including, but not limited to the following: our limited operating history; the need for, and our ability to raise, additional capital given our lack of current cash flow; our clinical and preclinical development, which involves a lengthy and expensive process with an uncertain outcome; our incurrence of significant research and development expenses and other operating expenses, which may make it difficult for us to attain profitability; our pursuit of a limited number of research programs, product candidates and specific indications and failure to capitalize on product candidates or indications that may be more profitable or have a greater likelihood of success; our ability to obtain and maintain regulatory approval of any product candidate; the market acceptance of our product candidates; our reliance on third parties to conduct our preclinical studies and clinical trials and perform other tasks; our reliance on third parties for the manufacture of our product candidates during clinical development; our ability to successfully commercialize Decoy20 or any future product candidates; our ability to obtain or maintain coverage and adequate reimbursement for our products; the impact of legislation and healthcare reform measures on our ability to obtain marketing approval for and commercialize Decoy20 and any future product candidates; product candidates of our competitors that may be approved faster, marketed more effectively, and better tolerated than our product candidates; our ability to adequately protect our proprietary or licensed technology in the marketplace; the impact of, and costs of complying with healthcare laws and regulations, and our failure to comply with such laws and regulations; information technology system failures, cyberattacks or deficiencies in our cybersecurity; and unfavorable global economic conditions. These and other important factors discussed under the caption “Risk Factors” included in our most recent Annual Report on Form 10-K filed with the SEC on March 17, 2023, and our other filings with the SEC, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. All forward-looking statements speak only as of the date of this press release and are expressly qualified in their entirety by the cautionary statements included in this press release. We undertake no obligation to update or revise forward-looking statements to reflect events or circumstances that arise after the date made or to reflect the occurrence of unanticipated events, except as required by applicable law. Contact: investors@indaptusrx.com Investor Relations Contact: CORE IR Louie Toma louie@coreir.com CORE IR Jules Abraham (media) 917-885-7378 julesa@coreir.com