Biologics

Immunotherapy Is Our Focus

Tivic is developing biologics based on its Entolimod™ platform, which activates innate immune pathways for cytoprotection and to modulate immune responses in conditions driven by radiation, disease, and immune dysregulation.

Entolimod™ is a selective Toll-like receptor 5 (TLR5) agonist that activates NF-κB signaling pathways through a cascade of cell signaling pathways, actively preventing programmed cell death (apoptosis) in both bone marrow and GI epithelial tissues.

The company’s lead drug candidate, Entolimod™ for Acute Radiation Syndrome, or ARS, has been extensively studied and has demonstrated robust survival data and improved tissue recovery in animal models under the FDA’s Animal Rule. Entolimod for ARS has been granted Fast Track and Orphan Drug designations by the US Food & Drug Administration. Its safety, efficacy, and animal-to-human dose conversion data allowed its progression with a pre-Emergency Use Authorization (EUA) application submission.

Entolimod™ represents a paradigm shift in the treatment of ARS. Entolimod’s dual-system protection shows the potential to offer a comprehensive survival benefit that currently approved and stockpiled G-CSF therapies [including Neupogen® (filgrastim), Neulasta® (pegfilgrastim), and Leukine® (sargramostim)] cannot provide. While these approved drugs are effective at stimulating the recovery of white blood cells after depletion, they do not address the lethal damage caused to the GI tract at higher radiation doses. This potential differentiation could make Entolimod™ a uniquely essential candidate for national defense and emergency response.

Data also show Entolimod is a radioprotective agent that may have the potential to be used prophylactically, or prior to exposure.

Latest Studies
Studies of Entolimod™ that are planned or are underway, are being sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), which is part of the National Institutes of Health. NIAID’s preclinical studies are designed to evaluate Entolimod’s ability to protect GI tissue and mitigate radiation-induced mucosal necrosis following exposure to lethal radiation doses, an area with limited therapeutic options, and a major driver of mortality in ARS.

These studies are expected to further define Entolimod’s potential and are typically required to support regulatory approval under the FDA’s Animal Rule.

In a Phase 3 study that was published in the peer-review journal Drug Discovery Today, Volume 26, Number 1, January 2021. Vijay K. Singh and Thomas M. Seed. Read Full Paper comparison of animal data to placebo showed:

Robust survival
- 40-60% survival advantage
- Similar magnitude of survival improvement when delivered 48 hours after irradiation
- 75% survival at 60 days vs 27.5 for placebo
Reduced apoptosis
Enhanced GI tract recovery
Better preservation/recovery of all parts of the intestine
Improved hematopoietic (creation of new blood cells) outcomes
Accelerated hematological recovery of peripheral blood

Oncology-Adjacent Treatments

Tivic is also advancing Entolasta™, a next-generation TLR5 agonist designed for potential broader therapeutic applications, including oncology supportive care. Tivic’s clinical pipeline includes potential treatments for neutropenia, which is most commonly caused by chemotherapy, and a state of T-cell dysfunction known as lymphocyte exhaustion.

Bridging Biodefense and Oncology: The Neutropenia Opportunity

The same mechanism that protects the body from high-dose radiation holds transformative potential for the multi-billion-dollar oncology supportive care market*. Myelosuppression and neutropenia (a severe depletion of white blood cells) are the primary dose-limiting side effects for a substantial number of patients undergoing chemotherapy and radiation.

Besides chemotherapy and radiation treatments, causes of neutropenia include chronic infection, autoimmune diseases, bone marrow disorders and aging.

Unlike existing standard-of-care treatments that reactively stimulate cell production after the damage has occurred, Entolimod™ is being developed as a protective agent to prevent cell death in the bone marrow. By mitigating the underlying tissue damage, Entolimod™ has the potential to:

reduce the incidence of life-threatening infections
minimize treatment delays,
and improve overall clinical outcomes for cancer patients.

Tivic is preparing to advance this program into physician-sponsored clinical trials later in 2026

Additional indications in development include:

Lymphocyte Exhaustion: Lymphocyte exhaustion is a state of functional decline and hypo-responsiveness in lymphocytes, such as T cells, caused by prolonged exposure to antigens or other inflammatory signals, often seen in chronic infections and cancers. This state is characterized by a loss of effector functions, decreased cytokine production, reduced proliferative capacity, and an increased expression of inhibitory receptors on the cell surface.

Immunosenescence: As the human body ages, it undergoes physiologic, biochemical, and hormonal changes that result in a less efficient and dysregulated immune response to pathogens. This aging process, termed Immunosenescence, renders elderly individuals more susceptible to infection, more likely to have a suboptimal response to vaccinations, and more likely to experience a chronic, proinflammatory state with a subsequent heightened activation of the systemic inflammatory response system to invading pathogens. Immunosenescence is incompletely understood, but involves changes to both the innate and adaptive immune systems.

* According to Data Bridge Market Research, the global neutropenia market is estimated to exceed $20 billion by 2029.