Biologics-2
Tivic’s biologics program is developing drugs that activate the immune system pathway to address radiation damage and immune decline.
Tivic’s lead drug candidate is Entolimod™ for acute radiation syndrome, or ARS.
About Entolimod™
Entolimod™ is a Toll-like receptor 5 (TLR5) agonist that activates NF-κB signaling pathways, with preclinical data suggesting the potential to protect epithelial and other tissues from radiation-induced damage. This differentiated mechanism may enable a broader cytoprotective effect across multiple organ systems, including the gastrointestinal (GI) tract, which is not addressed by the other currently approved drugs.
Data also show Entolimod is a radioprotective agent that may have the potential to be used prophylactically, or prior to exposure.
Entolimod™ for Gastrointestinal Acute Radiation Syndrome (GI-ARS)
Studies of Entolimod™ that are planned or 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.
Entolimod™ already has been the subject of extensive trials, which have delivered robust survival data. Entolimod for ARS has been granted Fast Track and Orphan Drug designations by the US Food & Drug Administration.
About Currently Approved Treatments for ARS
Currently approved ARS therapies, including granulocyte colony-stimulating factors such as Neupogen® (filgrastim), Neulasta® (pegfilgrastim), and Leukine® (sargramostim), primarily target the hematopoietic component of ARS following radiation exposure. However, damage to the GI tract is a key determinant of survival at higher radiation doses and is not directly addressed by these agents. GI injury remains a significant unmet need. Entolimod’s mechanism may offer a differentiated approach including protection of the GI tract.
Entolimod™ as a radiation countermeasure for Acute Radiation Syndrome
High doses of radiation exposure can result in life-threatening acute radiation syndrome, or ARS, as manifested by severe morbidity. Entolimod™ is effective in protecting against, and mitigating the development of, the hematopoietic and gastrointestinal subsyndromes of ARS in rodents and nonhuman primates. Entolimod™ treatment reduces radiation-induced apoptosis and accelerates the regeneration of progenitors in radiation-damaged tissues. The drug has been evaluated clinically for its pharmacokinetics, toxicity, and biomarkers.
The FDA has granted investigational new drug, fast-track, and orphan drug statuses to Entolimod™. Its safety, efficacy, and animal-to-human dose conversion data allowed its progression with a pre-emergency use authorization application submission.
This study was published in the peer-review journal Drug Discovery Today, Volume 26, Number 1, January 2021. Vijay K. Singh and Thomas M. Seed.
Entolimod for ARS has been granted Fast Track and Orphan Drug designations.
Entolimod for ARS Phase 3 animal data over placebo show:
- 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
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 the 60 percent of cancer patients undergoing chemotherapy and radiation.
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 currently preparing to advance this program into physician-sponsored clinical trials later in 2026.
According to Data Bridge Market Research, the global Neutropenia market is estimated to exceed $20 billion by 2029.
Additional indications in development include:
Neutropenia: Neutropenia is a condition characterized by lower-than-normal levels of neutrophils, a type of white blood cell essential for combating infections. Causes of neutropenia include chemotherapy and radiation treatments, chronic infection, autoimmune diseases, bone marrow disorders and aging.
According to Data Bridge Market Research, the global Neutropenia market is estimated to exceed $20 billion by 2029.
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.
Chronic Radiation Syndrome: Chronic radiation syndrome (CRS), is a constellation of health effects of radiation that occur after months or years of chronic exposure to high amounts of radiation. Chronic radiation syndrome develops with a speed and severity proportional to the radiation dose received (i.e., it is a deterministic effect of exposure to ionizing radiation), unlike radiation-induced cancer. It is distinct from acute radiation syndrome, in that it occurs at dose rates low enough to permit natural repair mechanisms to compete with the radiation damage during the exposure period. Dose rates high enough to cause the acute form (> ~0.1 Gy/h) are fatal long before onset of the chronic form.