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Samaritan
Partnered Its Phase II
SP-01A HIV Drug to Pharmaplaz, Ireland. |
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- $10M
Up-front ($1.4M March 2007, $8.6M Sept. 2007)
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Pharmaplaz Responsible for PIII Clinical Trial
Costs
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Samaritan to Receive 50% of Future Royalties
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“Drug Resistance” Market $500M,
Worldwide HIV Market $7B
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 SP-01A
Overview: SP-01A
is an adjunct oral, viral-entry inhibitor. It has
demonstrated significant efficacy in preventing viral
replication of the HIV virus, the causative agent
of AIDS. If used with any existing anti-retroviral
drug (ARV), SP-01A creates a firewall around a healthy
cell to prevent HIV entry. Studies have established
clear proof of concept for SP-01A.
Phase
I/II Study:
The safety and dose response of orally administered
SP-01A in HIV infected patients was assessed in this
30-patient, eight-week study.
SP-01A
demonstrated proof of concept with significance in
two crucial areas: a viral log drop of 1.32 (virus
undetectable-no adverse events) and improvement in
quality of life.
The
inhibitory effect of SP-01A on the entry of HIV and
multi-drug resistant HIV viral strains reinforced
our conviction that it targets the host cell, rather
than the virus itself, rendering SP-01A less susceptible
to emerging resistances than any other drugs on the
market.
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Phase
IIb/IIIa Monotherapy Study:
Samaritan has developed SP-01A as an adjunct therapy and
has performed pivotal Phase IIb/IIIa clinical human trials
for HIV “drug resistant” patients failing triple
therapy.
Samaritan
completed a 32-patient, 10-day (Segment One) Monotherapy
Study, “Multi-Center Double-Blind, Randomized, Placebo-Controlled
Study of Orally Administered SP-01A as Monotherapy Treatment
of HIV-Infected Patients”.
Samaritan also completed the enrollment of the 40-patient,
28-day (Segment Two) of this Monotherapy Study.
 SP-01A
MECHANISM OF ACTION
Prevents
HIV from entering healthy cells rather than treating the
disease after the infection has spread.
SP-01A
is an HIV oral entry inhibitor drug. In order for viruses
to reproduce, they must infect or hi-jack a cell, and use
it to make new viruses. Just as your body is constantly making
new skin cells, or new blood cells, each cell often makes
new proteins in order to stay alive and to reproduce itself.
Viruses hide their own DNA in the DNA of the cell, and then,
when the cell tries to make new proteins, it accidentally
makes new viruses as well. HIV mostly infects cells in the
immune system.
Clinical
studies to date suggest that SP-01A prevents HIV from entering
cells by inhibiting HIV-1 viral replication through a novel
mechanism that is unique to any antiviral drug. SP-01A reduces
intracellular cholesterol and corticosteroid biosynthesis,
which causes the inability of lipid rafts in the cellular
membrane to organize, ultimately preventing fusion of an HIV
receptor and both the CCR5 and CXCR4 cellular receptors.
On March
28, 2007, Samaritan and Pharmaplaz, announced that they have
a collaboration to develop and commercialize SP-01A, an "oral"
HIV entry inhibitor that has demonstrated safety and efficacy
in Phase II human clinical trials.
Under
the terms of the agreement, Samaritan receives $10 million
upfront in two payments. The first payment of $1.4 million
was received by Samaritan, and the remaining $8.6 million
is payable on September 16, 2007. Pharmaplaz will be responsible
for clinical development, clinical trial costs and manufacturing.
Upon successful commercialization, Samaritan and Pharmaplaz
will co-market SP-01A and will share 50-50 in its revenue
royalty stream.
As
a function of this modulation, we obtain the following benefits:
 1.
Both the CCR5 and CXCR4 receptor are conditioned and subsequently
antagonized;
2.
Fusion is inhibited by thwarting attachment of gp120 and gp41;
and
3.
Budding is inhibited.
As
a consequence of the above, SP-01A offers a decided advantage
in that there is less potential for susceptibility to the
development of resistance. Unlike currently approved antiretroviral
therapies, SP-01A conditions the cell membrane as opposed
to targeting the virus or its receptors directly.
Because
SP-01A is able to cross the blood brain barrier, the HIV virion
is unable to replicate or hide and will continue to circulate.
This continued circulation without viral replication, allows
the HIV-infected individual’s immune system and/or their
antiviral treatment regimen to eradicate the virus.
SP-01A
SUMMARY OF COMPLETED HIV TRIALS
 Phase
I/II Proof of Concept Study: An 8-week, Phase I/II study,
conducted at AIDS Research Alliance in Hollywood, CA, was
concluded and reported in July of 2003.
SP01A
was associated with reductions in HIV-1 viral load in patients
with measurable HIV-1 in a dose dependent manner. In the high
dose group, mean HIV-1 viral load reduction of 1.34 log10
copies/ml was observed; 100% of the patients achieved HIV-1
viral loads below the limit of detection and a greater than
1.0 log reduction was observed in 80% of the patients by Week
8.
This
level of reduction in viral load is clinically relevant, particularly
since patients continued on background antiretroviral therapy
throughout the clinical trial. Consistent with a treatment
effect of SP01A, HIV-1 viral load measurements showed a rebound
increase when high dose SP01A treatment was discontinued. |
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Table
1: Summary of Dose Groups and Cohorts
A
total of 29 individuals infected with HIV participated in
this study. Subjects received the following doses of SP-01A
and were divided into low dose and high dose groups for further
anti-viral analyses. Inclusion criteria for the study included
CD4+ count >200 and stable triple therapy antiretroviral
regimen for the preceding 8 weeks.
Treatment
changes for end of study treatment to baseline (Week 8 - Week
1) were compared to assess whether there was a dose response
between the high and low dose groups. Changes for post-treatment
(Week 10 - Week 8) were compared to assess whether there was
a "rebound effect" on observed changes after the
drug was removed.
Based on the clinically meaningful anti-viral changes and
SP-01A’s favorable safety profile observed during the
study, further examination of the higher doses of SP-01A in
future clinical studies is absolutely warranted.
Phase
IIb 10-Day Monotherapy Study (Stage 1):
SP-01A, an oral entry inhibitor, was tested "alone" in patients
experiencing HIV drug resistance.
The
study, a Phase II double-blind, placebo controlled, multi-dose
study in treatment-experience HIV patients, assessed SP01A's
safety and effect on viral load in HIV-1 positive individuals,
with evidence of increasing viral load, despite treatment
with antiretroviral therapy.
In
the preliminary finding, SP-01A was found to have a 0.4 log10
difference between the high dose group (800mg/day) and the
placebo control group. In addition, there was a dose dependent
relationship in the number of subjects who had a reduction
in viral load with the high dose group (800mg/day) showing
the most difference as compared to placebo (55% vs. 0%, respectively).
SP-01A Phase IIb, Segment 2 FDA Monotherapy
Clinical Trial:
SP-01A, an oral HIV Entry Inhibitor Drug, completed
a Phase IIb Monotherapy Trial:
SP01A:
The Study of an Oral Entry Inhibitor in Treatment-Experienced
HIV Patients
SP-01A Phase IIb,
Segment 1 FDA Monotherapy Clinical Trial:
SP-01A, an oral HIV Entry Inhibitor Drug, completed a Phase
IIb Monotherapy Trial:
A
Study of an Oral Entry Inhibitor, SP01A, in Treatment-Experienced
HIV-Infected Patients
SP-01A Phase Ib/IIa:
A
Dose Response and Safety Study of Procaine HCl in HIV-Infected
Patients |
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 The
HIV Virus:
In
order for viruses to reproduce, they must infect a cell. Viruses
are not technically alive: they are sort of like a brain with
no body. In order to make new viruses, they must hi-jack a
cell, and use it to make new viruses. Just as your body is
constantly making new skin cells, or new blood cells, each
cell often makes new proteins in order to stay alive and to
reproduce itself. Viruses hide their own DNA in the DNA of
the cell, and then, when the cell tries to make new proteins,
it accidentally makes new viruses as well. HIV mostly infects
cells in the immune system.
Infection:
Several different kinds of cells have proteins on their
surface that are called CD4 receptors. HIV searches for cells
that have CD4 surface receptors, because this particular protein
enables the virus to bind to the cell. Although HIV infects
a variety of cells, its main target is the T4-lymphocyte (also
called the "T-helper cell"), a kind of white blood
cell that has lots of CD4 receptors. The T4-cell is responsible
for warning your immune system that there are invaders in
the system.
Replication:
Once HIV binds to a cell, it hides HIV DNA
inside the cell's DNA: this turns the cell into a sort of
HIV factory.
Click
here to review The HIV Life Cycle |
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