Immune Modulating Drug Stimulates Innate Immunity, Down-Regulates Unproductive Inflammation and Promotes Th1 Immunity

by Dr. William M. Chamberlin

People have asked for more information on Formulated EpiBro (FepiBro).

A formulation of 16-bromoepiandrosterone (Epi-Br) was originally developed and investigated under the name HE2000.  There is extensive literature on its activity against infectious diseases. It underwent human trials as an immune modulating drug designed to combat the major infectious diseases in the “Developing World.” The HE2000 formula demonstrated activity against HIV/AIDS, malaria and tuberculosis in nine human trials. It was shown to be safe and effective.

Despite extremely promising results, politically motivated compulsory licensing stopped drug development. Acceptance by governing bodies of this well intentioned regulation meant that any company that developed a drug effective against an infectious disease in the developing world could be forced to license the manufacturing rights to other companies. In so doing, the immense cost of drug development could never be recouped. The World Health Organization did not oppose this politically popular move. Simple economics precluded further development of HE2000. In my opinion, although well intentioned and noble in spirit, political intervention into the economics of drug development cost humanity dearly.

Epi-Br is a synthetic analog of a naturally occurring steroid hormone with immune modulating properties. It enhances innate immunity and rebalances the immune network to limit excessive, destructive, inappropriate inflammation.  It polarizes the immune response toward a Th1, cell-mediated immune response necessary for effective immunity against intracellular microbial infections.  An effective cell-mediated Th1 response is required to control pathogenic mycobacteria infections. The original work with Epi-Br in animals and humans showed activity against many microbial pathogens.

There is strong evidence that Crohn’s disease results from a chronic mycobacterial macrophage infection.  The intricacies of the disease process on a molecular basis have not been entirely elucidated.  Therapeutically, enhancing the intracellular mechanisms inherent in the innate immune response should enable the immune system to contain the mycobacteria infection in Crohn’s disease as it has in other settings. The infection associated with Crohn’s disease should be controlled and provide relief to patients.

IMMUNIKAS is a newly formed company that has revived Epi-Br for use in Crohn’s disease because it is clearly associated with a mycobacteria infection. Mycobacteria bias the immune system to Th2 immunity as an immune evasive mechanism. In this instance Epi-Br was clearly shown as effective as anti-mycobacteria antibiotics. There are few known agents with Th1 promoting properties.

IMMUNIKAS will investigate the proven Epi-Br compound in an IK003 formulation, the first in a series of drug candidates potentially useful in treating infections that bias towards Th2 immunity. There is now a vastly improved proprietary formulation of the drug; formulation code IK004. This is planned as the next in a series of immune agents to treat Crohn’s disease. A pipeline of Th1 biasing immune agents is planned.

HE2000 has been used on HIV/AIDS patients who have contracted an opportunistic mycobacteria infection (tuberculosis), by treating the infection as the major life threatening disease. The underlying anti-inflammatory properties of the treatment are shown in Figure 1.  The effect of the compound in suppressing tuberculosis infection in a mouse model of tuberculosis is shown in Figure 2.  The effect of suppressing the activation of tuberculosis in AIDS patients is shown in Figure 3.



(Figure 1):  In HIV/AIDS, Epi-Br is an anti-Inflammatory agent. After dosing with Epi-Br, these patients experienced statistically significant declines in transcripts for TNF-alpha, COX-2, IL-1-beta and IL-6 as well as other inflammatory mediators.  The number of transcripts was normalized to levels close to those seen in healthy volunteers in four days and remained significantly reduced for the entire treatment course using only intermittent dosing.

Fig 1



 

(Figure 2):

Fig 2



 

(Figure 3):  Epi-Br prevents reoccurrence of tuberculosis in late stage HIV/AIDS patients.

TB occurred in 55% of patients in the placebo group and 21% in the HE2000 treated group, with no new episodes of TB experienced in the HE2000 group after 140 days.

The immune system was stimulated under the influence of HE2000. End-stage AIDS patients stopped developing clinical tuberculosis.  The population in this trial is infected with inactive tuberculosis and has an extremely high rate of reactivation of Mycobacterium tuberculosis.

Fig 3

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