Areas of Focus
Influenza/Colds/
Novel Respiratory Viruses
Our testing shows multiple MOAs and efficacy against the major influenza and other viruses. We believe that clinical trials will support use as a front line therapy and prophylaxis against endemic and novel respiratory viruses, including emerging threats of pandemic potential and bioweapons. We are discussing further development with the U.S. military and other government agencies.
We are developing a nasal spray that can be taken at first symptoms of any respiratory viral infection without requiring a diagnosis – with the potential to avoid severe cases and limiting transmission. It can also be used prophylactically by those who can’t or won’t take vaccines or who want or need added protection (no vaccine is 100% effective, especially the seasonal flu vaccines). Prophylactic use could be episodic (before getting on a plane, going to a ball game, going to a restaurant, etc.) or for continuous periods (e.g., by health care workers, other front-line workers, military living in close quarters, staff and residents in senior living centers, etc.).
Florescence-based activity assays show that TA (in a concentration only 1/4 the concentration proposed for the nasal spray) completely inhibited the activity of TMPRSS2 and human airway trypsin-like protease (HAT aka TMPRSS11D), which are essential for the replication of many of the respiratory viruses, including SARS-CoV-2. In addition, TA partly inhibited multiple other proteases, and inhibited the ACE2-spike protein connection by at least 60% in a Surface Plasmon Resonance (SPR) assay.
Additionally, our testing in the cancer field shows that TA occupies the cationic amino acid transporters (CATs) that are required to transport lysine, arginine and histidine into cells (because of their positive charge), thereby inhibiting the protein proliferation required for cancer growth. We believe this mechanism is also relevant for the protein proliferation involved in viral replication. Indeed, arginine deprivation in particular has been identified as a targeted therapy for SARS-CoV-2, although the agents envisioned reduce systemic arginine rather than simply depriving it from infected cells as would be the case with TXCA’s.
TA’s proven secondary effects are also relevant for its use against respiratory viruses:
- inhibition of plasmin formation (reduces virulence, inflammation, additional cleavage of the spike protein) while preserving plasminogen availability.
- anti-inflammation
- modulation of the innate immune system
- stimulation of mitochondrial function
- protection of the endothelium
- enhancement of the effect of antibiotics
A safe influenza drug that acts against host proteins rather than viral proteins, and thus avoids the ability of the virus to mutate and become resistant, has been sought for over two decades. We believe that the TA nasal spray will provide a significant benefit to global health by reducing the loss of lives and livelihoods, hospitalizations, other healthcare costs, and the risk of future pandemics.
Extensive method and composition patent filings covering synthetic analogs, derivatives, and mimetics, and the new nasal spray mode of administration provide protectability.
Conducting clinical challenge studies against the primary respiratory viruses followed by reasonably sized population studies will be a highly efficient way to handle the required clinical studies. Expedited handling by the FDA should be available.
Cancer
Our extensive in vitro and animal testing has shown that TA is effective against many types of cancer based on multiple methods of action. These results have been published in the peer-reviewed medical journal Frontiers in Pharmacology – Pharmacology of Anti-Cancer Drugs.
An initial focus is triple negative breast cancer (TNBC), because of our good preclinical results using TA against this cancer, and because there is a significant need for a more effective chemotherapy against it. Our novel TXCA has shown dramatic improvements in effectiveness against TNBC over TA and initial preclinical testing and IND enabling studies have been outlined.
We are also poised to conduct use of TXCA’s against squamous cell carcinoma because of its high incidence in the population, the negative side effects of the current treatments, and the fact that it can be treated topically. There are more cases of skin cancer than all other cancers combined. The most dangerous but least common is melanoma. The most common but least dangerous, because it does not metastasize, is basal cell carcinoma. In between is SCC, which metastasizes and results in 2 million cases annually in the US, with 15,000 deaths (more than melanoma). There is a similar incidence in Europe and an even higher incidence in Australia.
After diagnosis, one of several topical agents is often applied to try to reduce the size of the lesion so that excision is simpler and less disfiguring. However, there is no topical agent specifically approved for SCC, and the ones used off-label cause significant irritation, pain, redness and swelling. We expect that TA will effectively reduce the size of the lesions without side effects. Ideally, ongoing use of TA will completely eliminate SCC lesions and avoid surgery entirely.
If topical TA is effective against SCC, it may also be effective against Actinic Keratosis (AK), pre-cancerous scaly patches that lead to SCC about 20% of the time. Virtually every adult gets patches of AK at some point, with progressively higher incidence with age and exposure to sunlight. About 80% of people over 65 have AK.
Drug Combinations
Because of TA’s ability to treat a broad number of diseases either through direct effects or its significant secondary benefits described in Our Technology, the combination of TA with other drugs currently in use, in development, or that have failed in development represents a significant opportunity.
Benefits of combinations with TA include:
– Enhanced effectiveness
– Broader indications
– Lower dosage, allowing reduced toxicity, if applicable
– Reduced susceptibility to resistance
– Patent life extension or recovery for an approved drug
– Enhancement of an established brand or technology
– Rescue of a drug candidate that failed in a later stage of development
Concussion
Recent research has shown that concussion or mild traumatic brain injury involves fibrinolysis and inflammation similar to traumatic injuries involving more significant bleeding (Tagge et al., 2017), and that Tranexamic Acid offers significantly more anti-inflammatory benefits for TBI than the other antifibrinolytic drugs aprotinin and EACA (Wallen et al., 2022). We were recently awarded US patent rights covering methods and compositions of TA against concussion.
In addition, recent research has shown that standard intramuscular (IM) administration of TA provides a very favorable PK profile for TBI (OMori & Roberts, 2023), and the CRASH-4 trial is underway to study the benefits of TA in mild TBI in elderly patients. Finally, Abbott Laboratories recently received approval for use of a diagnostic device providing evidence of mild TBI based on blood biomarkers, providing a helpful tool for additional rapid concussion diagnosis/confirmation.
We are seeking partners to provide funding for a designed clinical trial program that initially tracks TA’s effects on certain biomarkers. Ultimately, the program’s goal is to mitigate the effects of a concussive event via short term use of TA or a new TXCA. Significant areas of focus are use by the military, sporting events, and ER visits for mild head trauma.
HSV
We have extensive in vitro and in vivo data showing that TA works very well against HSV-1 and HSV-2 and the MOAs involved, which include targeting host proteins. We have created a gel containing various concentrations of TA for the topical treatment of HSV.
No new herpes drug has been introduced in over 20 years, partly because herpes is not considered a life-threatening condition, and there are current medications that are “adequate”. However, all of those medications may work well for some, but their median efficacy is to reduce a 5 to 6 day outbreak by just half a day to one day. Thus many people get no discernible relief, and many have outbreaks that last two weeks or longer. Immunocompromised subjects such as transplant patients and those with HIV are particularly susceptible to HSV.
Healthspan
A recent study found that mice administered a standard oral dose of TA three times weekly for their entire lives had less inflammation and age-related diseases, and increased life span (Hiramoto et al., 2019). In addition, recent research shows that TA modulates the innate immune system, and it might reduce the incidence of Alzheimer’s Disease by inhibiting outbreaks of HSV, which have been tied to increased incidence of Alzheimer's. Our research indicates that TA is effective against a number of cancers and viruses.
TA is widely used on a monthly basis against heavy menstrual bleeding, and is used daily against hereditary angioedema. No adverse effects from daily long term use have been shown in those subjects or in animal studies. We have patents pending covering methods and compositions of TA and novel molecules against cancer and other diseases and promoting Healthspan. We are working with the University of Florida Dept of Physiology and Aging and have developed and study plan where doses of TA are administered orally and the effect on various biomarkers are tracked. We are actively seeking investors or partners to fund this and other related initiatives. Ultimately the goal is for the safe and long term administration of an oral therapy that increases life years lived free of serious disease.