Globally, the incidence of Types 1 and 2 herpesvirus infections is increasing. In the U.S., there will be an estimated 167 million adult patients with Type 1 (oral) herpes by 2023. According to WHO, more than 500 million people worldwide currently have Type 2 (genital) herpes. Young adults are experiencing the highest rate of new infections.
Market Impact: Worldwide prescription sales products to treat both oral and genital infections are slightly down from its $2 billion peak due to patent expirations of other products. BTL-tml is projected to achieve peak year sales of $260 million for the treatment of herpes labialis. Sales for other herpesvirus indications will be over and above this amount.
Safety: The daily use rate of microdose thimerosal is well below the daily exposure limits of the World Health Organization and the Environmental Protection Agency for mercury, a component of thimerosal. It has been tested in Beech Tree’s FDA-approved Phase 2a and 2b studies with no significant adverse events reported.
Efficacy: Beech Tree sponsored a Phase 2a clinical study in 2011 to test the hypothesis that thimerosal could prevent progression to lesion in patients experiencing prodrome symptoms following trauma induced by a dental procedure. In that study, 78 percent (7 of 9) of patients in the placebo group progressed to a lesion after experiencing prodrome while only 45 percent (10 of 22) progressed to lesion in the group treated with thimerosal.
Mechanism of Action: In in vitro Vero cell culture studies, BTL-tml-treated samples show a 20 to 40 percent reduction in infected cell plaques post HSV-1 infection. The mechanism was validated using in vitro mRNA expression data with results indicating that this agent downregulates the POLR2A gene, responsible for encoding the large subunit of RNA polymerase II, possibly leading to a stall in transcriptional activity of the host genome. BTL-tml also aids in the recruitment of leukocytes during viral infection through upregulation of RANTES.
Intellectual Property: U.S. and foreign patents have been issued for the use of thimerosal to treat herpesvirus infections.
Currently approved and marketed drugs do not block progression of an episode to lesion in a meaningful way. While the market to shorten the healing period of a lesion is populated with generic drugs, a product to block progression to lesion could breathe new life back into the herpes market. Reflecting additional potential applications of this anti-viral agent, the Company holds an open IND for a clinical trial focusing on influenza.