Small molecule drug candidate ST7-S

ST7-S – an oral small-molecule drug for mitigation of Acute Radiation Syndrome

Phoenicia BioSciences, Inc. and Boston University School of Medicine

Exposure to ionizing radiation (IR) as the result of nuclear terrorism or accidental exposure, such as occurred following the earthquake and tsunami in Japan in 2011, has become an increasing threat and concern. In New England, a large population over a wide geographic area is at risk of exposure in a nuclear plant accident in the aging faciities.  A recent interagency workshop on the radiobiology of nuclear terrorism has concluded that, in such an event, many victims may receive moderate doses of IR in the range of 1 to 10 Gy. Exposure to these doses of IR will cause significant civilian casualties due to IR-induced damage to normal tissues and subsequent complications. Without treatment, approximately half of all people exposed to a dose of more than 350 rad (3.5 Gy) will die within 60 days from complications of low blood cells, such as infection and bleeding, and gastrointestinal damage. In this context, new radioprotective agents that can be used as mitigating agents or treatments for post-radiation rescue therapy are needed.

The hematopoietic (bone marrow) and GI (gastrointestinal) components of the Acute Radiation Syndrome (ARS) are very important issues in the field of radiation countermeasures, since there are no approved drugs for treatment of ARS. Even assuming the availability of cytokines, growth factors, supplies for injection, and full medical support, there is still an urgent need to identify new treatments that will increase survival during ARS. There is a need to expand the repertoire of countermeasures to include agents that do not require clinical support and physician supervision, as such support has been shown to be problematic in realistic analyses of mass casualty scenarios. An ideal therapeutic would require a small, highly-stable molecule, preferably orally-active, with low toxicity and suitably stable for stockpiling in national and regional sites.

Phoenicia BioSciences has a molecule in preclinical development (designated ST7-S) which meets these requirements and has passed critical go-no go safety tests.

In extensive preclinical studies, we have found that:

  • ST7-S increases hematopoietic stem cell proliferation in multiple distinct murine and human assays
  • In irradiated mice, ST7-S given 24 hr later profoundly accelerates marrow recovery of all hematopoietic lineages (red and white blood cells and platelets). White blood cells  (neutrophils) are particularly needed to avoid fatal infection.
  • In lethally-irradiated miceoral ST7-S treatment for 4 days post-irradiation significantly increases survival (suggesting mitigating effects on both the Hematopoietic and the GI components of ARS).
  • In baboons and dogs, ST7-S increases absolute neutrophil counts and platelets, cells that make the blood clot and prevent bleeding
  • In anemic baboons and mice, ST7 increases red blood cells

ADVANTAGES of ST7-S over recombinant peptide growth factors include:

  • Multi-lineage hematopoietic activity
  • Oral bioavailability (parenteral injection not required)
  • Stability at ambient and elevated temperature (easily stored/shipped and stockpiled; refrigeration not required)
  • Once-daily dosing predicted at (tolerable) human equivalent doses (HED) of between 350 and 1500 mg for an average 70 kg adult And teaspoon or single tablet doses from children

New US Patent Awarded for Hemoglobinopathy Program

Phoenicia Scientists were awarded a new US patent (8,759,378, Issued June 24, 2014: “Methods for Treating Blood Disorders”), covering newly-discovered small molecules which regulate fetal globin production for the treatment of β-thalassemia and sickle cell disease

Therapy for EBV-associated Lymphomas

A virus-targeted therapy for
Epstein Barr virus associated lymphomas  

Phoenicia is working to bring an innovative therapeutic approach for deadly EBV-associated lymphomas into clinical trials with a new generation and oral virus-targeted therapeutic.

Epstein Barr virusPhoenicia Founder Douglas V. Faller developed a method to activate silent genes within the dormant EBV virus, which resides in lymphoma cells.

The EBV virus, whether a “passenger” or the cancer-causing agent, can then serve as a target for therapeutics. Activating the viral TK gene causes activation of a common antiviral pro-drug, selectiving killing the lymphoma cells containing the virus.  Continue reading

Refractory Wound Therapeutic NIH Grant

NIH grant to convert a potent IV
therapy for refractory wounds into
a topical formulation

Phoenicia has received a new small business grant from the National Institutes of Health for studies to convert an intravenous therapy which healed refractory, disabling leg ulcers in hemolytic anemias, sickle cell disease and β-thalassemia, into a topical preparation which can be used readily by patients world-wide. Continue reading