Biologics
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 novel TLR5 agonist that triggers NF-kB signaling. It activates antiapoptotic (a series of molecular steps that lead to cell death) and cell protective mechanisms.
Tivic is developing Entolimod for ARS under the FDA’s animal rule. Entolimod has been the subject of extensive trials, which have delivered robust survival data. Additionally, and key to differentiate it from other ARS treatments, Entolimod™ has shown enhanced gastrointestinal (GI) tract recovery (through the stimulation of GI cell regeneration) and improved hematopoiesis (the formation of blood’s cellular components), potentially leading to better systemic outcomes.
Data also show Entolimod is a radioprotective agent that can be used prophylactically (prior to exposure). Entolimod for ARS has Fast Track and Orphan Drug designations.
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
Other indications:
Tivic also holds the exclusive rights for Entolimod for the treatment of neutropenia and has the option to license additional indications, including lymphocyte exhaustion, immunosenescence, and chronic radiation syndrome.
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.