Quark Pharmaceuticals Reports Favorable Results From Phase II Clinical Trial Evaluating Investigational siRNA QPI-1002

Quark Pharmaceuticals Reports Favorable Results From Phase II Clinical Trial
Evaluating Investigational siRNA QPI-1002

Data on siRNA for the Prophylaxis of Delayed Graft Function in Deceased Donor
      Kidney Transplant Patients Presented at World Transplant Congress

    Proof of Concept for First-in-Class Systemically Delivered siRNA-based
                           Transient p53 Inhibitor

SAN FRANCISCO, July 28, 2014 (GLOBE NEWSWIRE) -- Today, Quark Pharmaceuticals,
Inc. reported data from a randomized, double-blinded, placebo-controlled
multicenter Phase II clinical trial (QRK.006B; ClinicalTrials.gov identifier:
NCT00802347) of QPI-1002, a synthetic chemically modified siRNA acting to
reduce p53 RNA and protein levels, for the prophylaxis of delayed graft
function (DGF) in deceased donor kidney transplant patients. The data were
presented in the late-breaking session at the 2014 World Transplant Conference
(WTC) in San Francisco, CA by Dr. V. Ram Peddi, Director of Kidney Transplant
Research at California Pacific Medical Center in San Francisco, on behalf of
the QPI-1002 DGF Study Investigator Group.

The study, which included 331 treated (327 efficacy evaluable) patients, was
conducted in 52 transplant centers across North America and Europe. The
primary objectives of the study were to assess the efficacy of QPI-1002 in the
prevention of DGF and to further assess its safety and pharmacokinetics. The
primary study endpoint was to achieve at least 30% relative risk reduction of
DGF (defined as the need for dialysis within the first 7 days post-transplant,
excluding dialysis in the first 24 hours due to hyperkalemia/hypervolemia) in
QPI-1002-treated patients compared to placebo.

The overall QPI-1002 safety profile was consistent with the expected profile
for transplant recipients, and similar in both treated and placebo groups.
While the primary endpoint for the study was not met in the total study
population (15.1% relative risk reduction of DGF), the data presented at the
WTC showed that treatment with QPI-1002 resulted in 30.5% relative risk
reduction in patients included in the largest of the prospectively defined
study strata - Expanded Criteria Donor kidneys entirely Cold Stored (ECD/CS,
n=177,). The same relative risk reduction of approximately 30% was obtained,
in post hoc analysis of the results, in all recipients of kidney grafts from
donors older than 45 or 35 years of age, n=252; 77% and n=283; 86%
respectively of all efficacy evaluable patients, regardless of the predefined
graft strata classification (data for older than 35 not presented at the WTC).

Furthermore, in the ECD/CS stratum, QPI-1002 treatment significantly increased
the dialysis free survival (time to first dialysis) in the first
post-transplant month (Log rank p=0.04), reduced the mean duration of the
first course of dialysis (13.4 vs 25.3 days); and reduced the number of
dialysis sessions required in the first 30 days post-transplant (6.0 vs 11.2).
Similar results were obtained in all recipients of kidney grafts from donors
older than 45 and in patients receiving kidneys of donors older than 35 years
of age, regardless of the predefined graft strata classification (data for
older than 35 not presented at the WTC). By the end of 6-month study
observation period, the total number of dialysis sessions in all efficacy
evaluable patients treated with QPI-1002 was 1.5-fold lower compared to
placebo group (375 vs. 561 p=0.059).

The improved outcomes associated with QPI-1002 treatment in the function of
kidney grafts from older donors is consistent with recently published
studies^1 showing stronger activation of p53, the target of QPI-1002,
following reperfusion of older kidneys in animal models. Altogether, the trial
findings justify continued development of QPI-1002 for the prevention and
amelioration of DGF, an unmet medical need. In addition, increased impact of
kidney age on treatment outcomes of QPI-1002 indicates that this drug may be
useful for prophylaxis of acute kidney injury in patients undergoing major
cardiac surgery given the higher prevalence of this procedure in aging
population. Quark believes that QRK.006B is the first ever well-controlled
clinical trial involving hundreds of patients in which a systemically
administered siRNA-based drug has shown clinical activity.

"Delayed graft function adversely affects outcomes following deceased donor
kidney transplantation and is a significant problem for which there is no
approved treatment. Quark Pharmaceuticals' study with QPI-1002 is a very large
double-blind randomized study in patients at risk for DGF," Dr. Peddi
observed. "The findings of this study showing QPI-1002 decreases DGF,
especially in older donor transplants, are exciting and warrant further study
with this investigational agent that could improve outcomes from older
kidneys."

Dr. A. Osama Gaber, F.A.C.S, Professor of Surgery of the Houston Methodist
J.C.Walter Jr. Transplant Center, an investigator in the study who previously
presented the Phase I QPI-1002 results, stated, "QPI-1002 represents a truly
unique approach by directly targeting p53-dependent cell death, an underlying
trigger of the injury that causes DGF, and the findings in older donors
support the rationale for a QPI-1002 treatment effect based on p53 expression
in older kidneys. The positive findings in this large trial merit further
study, and suggest we may have a promising investigational agent for DGF."

About the QRK.006 trial

The QRK.006B Phase II study was a multicenter placebo-controlled, randomized,
prospective, and double-blinded for evaluating the clinical activity of
QPI-1002 (administered as 10 mg/kg single bolus IV dose at 30 minutes after
circulatory reperfusion is achieved to the transplanted organ) in end-stage
kidney disease dialysis-dependent patients undergoing deceased donor kidney
transplantation. The primary objectives of the study were to assess the
efficacy of QPI-1002 in the prevention of DGF and to further assess its safety
and pharmacokinetics. The incidence of DGF (defined as the need for dialysis
within first 7 post-transplant days excluding dialysis in the first 24 hours
due to hyperkalemia/hypervolemia) was the primary study endpoint, whereas
secondary endpoints included other definitions of DGF, and parameters
evaluating DGF severity and kidney function in the post transplant period. The
patients were prospectively grouped into 4 strata by the type of donor -
expanded or standard criteria donors (ECD or SCD); and graft preservation -
cold-stored (CS) or machine-perfused (MP) with protocol specified cold
ischemia time (CIT requirements).

About Delayed Graft Function (DGF)

DGF results from ischemia-reperfusion injury to the graft tissue associated
with transplantation procedure when blood flow is re-established to the kidney
following transplantation and initiates a chain of events that can lead to
severe renal damage. DGF not only significantly increases the risk of delayed
allograft rejection, but also adds to the cumulative cost of renal
transplantation by increasing the time of hospital stay, the number of tests
and the use of dialysis facilities. The increasing shortage of suitable kidney
donors led to the necessity of incorporating expanded criteria donor kidneys
(mainly from older deceased donors) into the donor pool. However, such kidneys
are at increased risk of DGF. There is no currently marketed drug therapy for
the prevention or treatment of DGF.

About QPI-1002

QPI-1002, the first systemic siRNA drug to enter human clinical trials and to
complete a well-controlled clinical trial with clinical efficacy endpoints
that was conducted in hundreds of patients. It is an investigational drug
designed to temporarily inhibit the expression of the pro-apoptotic gene, p53,
to protect normal cells from acute injury. Preclinical studies have shown that
p53-targeted siRNAs can protect kidneys from ischemia/reperfusion injury in a
variety of clinically relevant animal models. QPI-1002 has been granted Orphan
Drug designation in the USA and Europe for the prevention of DGF in kidney
transplant patients. Under an August 2010 agreement, Novartis has an exclusive
worldwide license option for the development and commercialization QPI-1002.

About Quark Pharmaceuticals, Inc.

Quark Pharmaceuticals, Inc., is one of the world leaders in novel therapeutic
RNAi discovery and development. The Company's fully integrated drug
development platform spans from therapeutic target identification to drug
development. Quark has three siRNA product candidates in clinical development
in five different disease indications of which four are in Phase II. Quark's
Joint venture in China, Kunshan Ribo-Quark Pharmaceutical Inc, and its
strategic partner in India, Biocon Limited, are part of Quark's worldwide
clinical studies network. 

Quark is headquartered in Fremont, California and operates research and
development facilities in Boulder, Colorado and Ness-Ziona, Israel. For
additional information please visit: www.quarkpharma.com

^1 Clemens et al. (2013). Increased cellular senescence and vascular
rarefaction exacerbate the progression of kidney fibrosis in aged mice
following transient ischemic injury. PLOS ONE, 8, e70464. Fan et al. (2013).
The histone deacetylase, SIRT1, contributes to the resistance of young mice to
ischemia/reperfusion-induced acute kidney injury. Kidney International 83,
404–413.

CONTACT: Quark Pharmaceuticals, Inc.
         Juliana Friedmann
         +972 89 30 5111
         jfriedman@quarkpharma.com
 
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