Company: INDP
Filing Date: 2025-03-13
Form Type: 10-K
Source: 0001493152-25-010136
Chunk: 10

Company: Indaptus Therapeutics, Inc.
Filing Date: 2025-03-13
Form: 10-K
Item: Item 1
Chunk 10
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 safety margin. Induction of adaptive anti-tumor immune responses and immunological memory by
our technology does not require an exogenous tumor antigen.

11

Innate
and adaptive immune responses require identification of a tumor as foreign or not self. However, most steps required for migration and
activation of immune cells are unrelated to the tumor or are tumor non-specific. All innate and adaptive non-specific steps are induced
or promoted by immune system “danger signal” molecules, such as those found in our bacteria. Bacteria-derived danger signals
are also able to enhance the processing and recognition of tumor antigens, which are frequently present, but not “seen” by
the immune system.

Results

Preclinical
Trials

In
preclinical models, Indaptus treated bacteria induced less systemic toxicity than untreated bacteria but were still able to activate
innate and adaptive immune responses. Despite exhibiting reduced in vivo pyrogenicity and a higher maximally tolerated dose, our bacteria
were able to induce secretion of most cytokines and chemokines from mouse and human immune cells in vitro at levels comparable to those
seen with untreated bacteria. Our bacteria were also able to synergize with human immune cells to kill human tumor cells in vitro.

We
have observed significant single agent anti-tumor activity and/or combination therapy-mediated regression with durable responses in established
non-Hodgkin’s lymphoma, as well as colorectal, hepatocellular and pancreatic carcinoma in preclinical syngeneic and human tumor
xenograft models. Our bacteria synergized with each of four different classes of approved agents in preclinical models, including NSAIDs,
checkpoint therapy, targeted antibody therapy and low-dose chemotherapy to induce tumor regression, providing significant flexibility
for targeting of diverse types of cancer. Our technology is designed to eradicate tumors via activation of both innate (NK cell) and
adaptive (CD4+ and CD8+ T cell) mechanisms, with the goal of producing both innate and adaptive immunological memory. In our preclinical
studies, tumor eradication occurred at non-toxic doses of our bacteria, with a very wide (10 to ≥33-fold) therapeutic index. Notable
mechanism of action information has also been obtained, via gene expression analysis with treated tumors and plasma cytokine analysis,
demonstrating that our combination technology has the potential to turn “cold” tumors into “hot” tumors and induce,
activate or recruit innate and adaptive genes, cells and pathways. Immune cell pre-depletion studies