B50 as the Next Lead Candidate for hematopoiesis

Plants Screened

A total of 21 herbs used in TCM tonics were selected, extracted and screened for hematopoetic potential using in vitro assays for cytokine production.  Extracts from as many as 15 of these plants were found to be highly active at inducing G-CSF production in human peripheral blood mononuclear cells.  Extracts from 13 of these plants were tested in animal models for hematopoietic activity.  Initial in vivo studies showed that 6 of them demonstrated promising activity in promoting early recovery of peripheral blood from radiation- or chemotherapy-induced myelosuppression in mice, and in stimulating recovery of hematopoietic progenitors from these therapies.  This is a remarkable hit rate compared to typical pharmaceutical screening.  One plant, B2, was selected and studied in greater detail by further fractionation and purification for chemical analysis and biological activity confirmation.  This process of guiding plant extract fractionation and purification by biological activity led to the generation of PG2 from the B2 plant.  B50 is potentially the next source of a hematopoetic drug candidate.

B50 is frequently employed in TCM.  Extracts prepared from B50 were tested both in vitro and in vivo, and had generated promising results.  These studies showed that B50 extracts had immune potentiating activities as well as hematopoietic stimulatory activities.  The extracts stimulated mutilineage hematopoietic recovery from radiation- or chemotherapy-induced myelosuppression in mice and the recovery in PLTs was the best among the three lineages. B50 extracts alleviated thrombocytopenia associated with the therapies and promoted a much earlier recovery of PLT counts than the control untreated mice. 

Market Overview

The destruction of blood cells is a common liability of many cancer therapies, including both chemotherapy and radiation therapy.  Unfortunately, while killing cancer cells, these therapies kill normal cells as well, including precursors to WBCs, RBCs and PLTs), leaving patients extremely vulnerable to infection and anemia, as well as being prone to excess bleeding due to an insufficiency of PLTs.  Thrombocytopenia is a common medical problem for which the main treatment is PLT transfusion.  However, PLT transfusion therapy is associated with several problems, including refractoriness and alloimmunization, transmission of infectious agents, and transfusion reactions.  Due to the increasing use of PLTs and the declining donor population,  PLT renewal remains an unmet medical need and identification of a safe and effective platelet product is in high demand.  Although two proteins, IL-11 (approved) and thrombopoietin (in development) hold some promise, it is not certain that these agents will prove to be safe and effective.  Moreover, they will share a major limiting liability -- as proteins they are expected to be very expensive.  PG50, therefore, has been chosen as the next lead candidate in the field of hematopoiesis, with the emphasis on PLT restoration.

PG50 in Platelet Restoration

In preliminary screening studies, extracts of the B50 plant stimulated the in vitro production of hematopoietic cytokines by human peripheral blood mononuclear cells as well as B2 extracts.  Furthermore, on a broad scale the hematopoietic stimulating capacity of B50 extracts was of a similar magnitude to B2 extracts in promoting early recovery of peripheral blood from myelosuppression in mice. In subsequent in vitro and in vivo studies of efficacy, PG50 had both hematopoietic stimulatory activities and immune potentiating activities.  PG50 stimulated mutilineage hematopoietic recovery from radiation- or chemotherapy-induced myelosuppression in mice.  Among the three lineages of blood cells, the recovery in PLTs was the best. PG50 treatment alleviated thrombocytopenia associated with the therapies and promoted a much earlier recovery of PLT counts than the control untreated mice. 

Clinical Development of PG50

The strategy for the development of PG50 will be oriented toward potentiation of hematopoietic recovery, with an emphasis on PLT restoration. An intravenous formulation will be developed, with the possibility of an oral formulation for less intense, long-term administration subsequently.  Pharmagenesis will seek a partner for later stages of development of PG50 in PLT restoration by hematopoietic stimulation.

 

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