Indaptus Therapeutics’ Pioneering Research on Novel Immunotherapy Approach Published in Peer-Reviewed Frontiers in Immunology

Indaptus Therapeutics, Inc. (Nasdaq: INDP) (“Indaptus” or the “Company”), a clinical stage biotechnology company dedicated to pioneering innovative cancer and viral infection treatments, announced today that Dr. Michael Newman, Founder and Chief Scientific Officer, has published his groundbreaking research in the peer-reviewed journal, Frontiers in Immunology. The article, titled "Invention and Characterization of a Systemically Administered, Attenuated and Killed Bacteria-Based Multiple Immune Receptor Agonist for Antitumor Immunotherapy," presents the Company’s innovative approach to activating both the innate and adaptive sides of the immune system to treat cancer. The paper is being published as part of a Research Topic on The Vital Role of Innate Immunity in Cancer Immunotherapy.

This publication describes the invention and pre-clinical characterization of the Decoy platform, including Decoy20, a novel clinical stage immunotherapy candidate. Decoy20 leverages attenuated, killed and stabilized bacteria to activate multiple immune pathways with a weekly pulse, aimed at creating a comprehensive immune response against tumors. By priming or activating both the innate and adaptive immune systems, Decoy20 has demonstrated the potential to enhance immune responses to effectively fight various types of cancer, including colorectal, pancreatic, hepatocellular cancers and lymphomas. Dr. Newman’s study highlights Decoy20’s potential advantages over traditional treatments, such as chemotherapy, as well as its potential to significantly enhance the efficacy of current, single-target immunotherapy, because it triggers a broad yet controlled activation of the immune system while reducing toxicity often seen with other cancer immunotherapies.

Dr. Newman commented, “It is incredibly rewarding to have our work recognized in such a prestigious publication. I am honored to share years of scientific research with the broader scientific community, contributing a deeper understanding of our ‘pulse-prime’ approach to enhancing both innate and adaptive immune activation. We believe this methodology, represents a significant step toward more effective cancer immunotherapy.”

Jeffrey Meckler, CEO of Indaptus Therapeutics, commented, "We are pleased to share Dr. Newman's valuable contribution to immunotherapy research, which aligns with Indaptus’ mission to redefine cancer treatment. This publication not only strengthens the science behind Decoy20, but also showcases the transformative potential of our Decoy platform to address some of the most challenging cancers. Our recently announced agreement with BeiGene will allow us to further explore these promising findings by combining our Decoy20 with their anti PD-1 checkpoint inhibitor, tislelizumab. We are excited to advance this work and bring new hope to patients in need."

Key Highlights from the Research:

• Multi-Pathway Immune Activation: Unlike traditional immunotherapies that focus on a single immune pathway, Decoy20 engages multiple immune receptors, including Toll-like, NOD-like, and STING receptors, to initiate a broader and more durable immune response.
• Encouraging Preclinical Data: Decoy20 has produced efficacy in preclinical studies across a variety of tumor types and in combination with four different classes of existing drugs, demonstrating both innate and adaptive immune activation that led to tumor regression and immunological memory.
• Reduced Toxicity Profile: By using a rapidly cleared, bacteria-based delivery package and significantly lowering but leaving a small amount of immune activating LPS-endotoxin activity, Decoy20 is designed to produce a broad, but transient or pulsed activation of innate and adaptive immune pathways, minimizing toxicity and enabling safe systemic administration - a longstanding challenge with novel cancer immunotherapies.

Dr. Newman, added, “Being published in Frontiers in Immunology is an important milestone that reinforces the promise of our Decoy platform to potentially redefine immunotherapy. We’re encouraged by our preclinical and clinical findings, and we look forward to continuing to advance Decoy20 in clinical trials, where we hope to see its unique immune-activating properties translate into meaningful patient outcomes.”

As Indaptus moves forward with clinical development, this publication underscores the company’s commitment to advancing innovative science to meet the urgent need for more effective and tolerable cancer treatments. Indaptus is currently enrolling patients in its Phase 1 clinical trial of Decoy20, targeting a range of advanced solid tumors, and plans to roll out its trial combining Decoy20 with BeiGene’s tislelizumab next year.

For more information, please visit the full publication here: https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1462221/full

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), Nucleotide oligomerization domain (NOD)-like receptor (NLR) and Stimulator of interferon genes (STING) agonist Decoy platform. The product candidates 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 product candidates 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, pancreatic 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 product candidates 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 candidate, with associated “cold” to “hot” tumor inflammation signature transition. The Decoy platform has also been shown to induce activation, polarization or maturation of human macrophages, dendritic, NK, NKT, CD4 T and CD8 T cells in vitro. IND-enabling, nonclinical toxicology studies demonstrated 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 candidate. Indaptus’ Decoy product candidates have also produced meaningful 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 within 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 our clinical supply agreement with BeiGene; our plans to advance clinical evaluation of the combination of BeiGene's anti-PD-1 antibody, tislelizumab, with Decoy20; our plans to seek FDA approval and to initiate a combination trial; the anticipated effects of our product candidates, including Decoy20; the plans and objectives of management for future operations; our research and development activities and costs; the sufficiency of our cash and cash equivalents to fund our ongoing activities and our cash management strategy; and our assessment of financing options to support our corporate strategy. 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; conditions and events that raise substantial doubt regarding our ability to continue as going concern; 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 Quarterly Report on Form 10-Q for the quarter ended June 30, 2024 filed with the SEC on August 12, 2024, our most recent Annual Report on Form 10-K filed with the SEC on March 13, 2024, 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.

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