Artemisone is a novel, synthetic derivative of artemisinin which has been optimized for potency, stability, and safety. It is a member of a class of drugs named artemisinins, which are the global backbone treatment for malaria throughout the world. More recently, certain artemisinins have also shown potential as anti-viral therapies. Artemisone was originally synthesized and tested clinically by Bayer HealthCare AG under a research collaboration with the Hong Kong University of Science and Technology (HKUST). Artemis Therapeutics owns an exclusive, worldwide license agreement with HKUST and Hadassah Medical Center for intellectual property (i.e. patents) and know-how pertaining to the manufacture, use, and commercialization of Artemisone.
Phase II clinical data has shown Artemisone to be an efficacious treatment for P. falciparum malaria infection when dosed over a 2-day or 3-day course, similar to or shorter than other available malaria treatments. As recommended by the World Health Organization (WHO), a second anti-malarial drug is also given on the final day of artemisinin treatment. In this 95-patient Phase II study, cure rates of 100% were observed at 28 days following both the 2- and 3-day course of Artemisone.
In a clinical case study in a patient with ganciclovir-resistant and foscarnet-resistant CMV (i.e. a DNA polymerase mutation), artesunate, a different member of the artemisinin class, proved to be a highly effective inhibitor of CMV replication and resulted in a 2-log reduction in viral load by treatment day 7, indicating a highly effective block in viral replication. Notably, Artemisone has been shown to be 10-fold more potent than artesunate in in vitro CMV models. Artemisone also has been shown to inhibit CMV viral replication with similar or better potency than ganciclovir, the current treatment of choice for CMV patients. Furthermore, Artemisone appears to show extremely low propensity to generate viral mutations that would produce resistant strains of CMV.
The mechanism of action of Artemisone in suppressing viral replication is unique when compared to currently-available treatments for CMV and treatments currently in development for CMV, which offers opportunities for first-line and/or combination treatments of CMV, including in stem cell transplant, solid organ transplant, and congenital CMV patients.
Malaria is endemic in 91 countries worldwide. According to the World Health Organization Malaria Report published in December 2016, there were 229 million cases of malaria worldwide in 2015 resulting in 429,000 deaths. The disease burden is of particular significance in sub-Saharan Africa, which accounts for 90% of the cases and 92% of the mortality worldwide. South-East Asia, Latin America and the Middle East are also areas where there is a significant malaria risk.
Artemisinin and its derivatives such as artesunate, artemether, arteeter and dihydro-atemisinin (DHA) have for many years been the backbone of treatment of uncomplicated P. falciparum malaria. Parenteral forms of these drugs are also used for the treatment of severe malaria and cerebral malaria, conditions where patients are frequently unable to swallow. Currently available artemisinins used to treat malaria have limitations due to the emergence of resistant strains and the association of current artemisinins with neurotoxicity, their poor thermal stability and their potency.
Human Cytomegalovirus (HCMV) in Transplant Patients
Artemisinins derivatives have been found to have anti-viral properties, in particular against Human Cytomegalovirus (CMV), a double-stranded DNA virus that is normally latent in healthy sero-positive individuals but which frequently reactivates in immuno-compromised individuals such as patients having undergone Hematopoietic Cell Transplant (HCT) or Solid Organ Transplant (SOT). Patients who are sero-negative for CMV but who receive a graft from a sero-positive donor are particularly at risk.
In such individuals, CMV reactivation or infection can result in CMV disease of the eyes, lungs, gastrointestinal tract and Central Nervous System. In its severe forms, end-organ failure can result. In addition, even in the absence of signs and symptoms, reactivation of CMV in HCT recipients has been associated with a two-fold increase in mortality risk. Reactivation of CMV in SOT recipients is associated with an increased incidence of acute graft rejection. Current treatments for CMV in transplant patients have limitations in terms of toxicity.
There are approximately 80,000 HCT’s performed worldwide each year with this number expected to grow. The worldwide number of SOT’s performed annually is currently in the order of 115,00.
Human Cytomegalovirus (HCMV) in neonates (Congenital CMV)
HCMV affects newly born babies who are infected by their mothers in utero (Congenital CMV). Neonates who develop CMV disease are at heightened risk for suffering from a variety of developmental disorders such as sensorineural, vision loss, intellectual disability, lack of coordination, muscular weakness and seizures. HCMV is the leading non-hereditary cause of sensorineural in infants. Current treatments for Congenital CMV are limited by toxicity and there is a significant unmet need for treatments that can safely be administered to neonates.
The incidence of Congenital CMV in the United States is approximately 1%. This means that of almost 4 million live births annually, 40,000 babies will be born with CMV. Of these, 4,000 will be symptomatic and at highest risk of developing significant clinical sequelae. Of the non-symptomatic babies, 15% (5,400) will also subsequently develop significant clinical sequelae.