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Isotechnika Inc.

Isotechnika Presents Positive Data From the Promise Trial of Voclosporin at the American Transplant Congress

Edmonton, Canada (ots/PRNewswire)

Isotechnika Inc. today
announces the successful results of the Phase 2b PROMISE trial which
were presented by Dr. A. Osama Gaber, an investigator for the PROMISE
trial, at the 2008 American Transplant Congress in Toronto, Canada.
The presentation detailed the final data confirming the efficacy of
Isotechnika's next generation calcineurin inhibitor, voclosporin
(ISA247), in de novo kidney transplant patients. An improved safety
profile versus tacrolimus was also reported. Dr. Gaber is the
Director of Transplantation, Vice-Chair for Administration and
Faculty Affairs, Department of Surgery, The Methodist Hospital
(Houston) and Cornell University (New York).
"Despite the advances in transplant medicine which have allowed
patients to lead healthier, more fulfilling lives, there is still an
unmet medical need in these patients, and room for improvement in the
drug regimens used to preserve organ function," stated Dr. Gaber. "In
this study, voclosporin demonstrated encouraging results with regards
to both efficacy and safety parameters, specifically new onset
diabetes mellitus."
Calcineurin Inhibitor Market
Tacrolimus is the global market leader in transplant, garnering
about 75% of the US calcineurin inhibitor market. Calcineurin
inhibitors are a core part of the drug regimen of kidney transplant
patients, 93% of whom receive a calcineurin inhibitor. Worldwide, the
calcineurin inhibitor market is currently approximately CND$2.8
billion, and expected to grow to  CND$4 billion by 2010.
Efficacy
In PROMISE, the primary endpoint (biopsy proven acute rejection,
BPAR) was clearly met in all three voclosporin dose groups. BPAR is a
measure of acute rejection in transplant. In clinical practice,
patients with more episodes of BPAR, typically 10-15% at 6 months,
have worse outcomes. The results show that voclosporin is as
efficacious as tacrolimus, has the dose response expected in a Phase
2 trial, and provides the rationale for dose selection for the Phase
3 clinical program.
    Drug                                               Patients with BPAR
    Low dose voclosporin                                           11%(x)
    Mid dose voclosporin                                            9%(x)
    High dose voclosporin                                           2%(x)
    Tacrolimus                                                         6%
    (x)statistically non-inferior to tacrolimus
Safety
The three dose groups of voclosporin were shown to be safe.
Voclosporin demonstrated improvements over tacrolimus in several key
areas, specifically with respect to NODM, triglycerides, magnesium,
insomnia and tremors.
New Onset Diabetes Mellitus (NODM)
NODM is a serious complication in transplant patients and
negatively impacts patient outcomes. Published literature shows that
mean graft survival of 11 years decreases to 8 years with NODM.
A statistically significant lower incidence of NODM was seen in
the low dose voclosporin group, translating into a 90% reduced risk
of developing NODM as compared to tacrolimus. Although not
statistically significant, the mid dose group had a clinically
meaningful lower incidence of NODM with a 65% reduced risk. The high
dose group had an incidence of NODM that was not clinically different
than tacrolimus. This reduced burden of NODM in the low and mid dose
groups represents a large benefit to patients.
Triglycerides
Triglyceride elevation is risk factor of cardiovascular
complications. The low dose voclosporin group showed a statistically
significant reduction in the number of incidences of elevated
triglycerides compared to tacrolimus translating into a 55% risk
reduction. The mid and high dose groups showed a 24 to 30% reduced
risk of elevated triglycerides.
Magnesium
Magnesium is involved in many important functions in the body,
and is regulated by the kidneys. Low magnesium levels can lead to
cardiac arrhythmia, hypertension, muscle cramps, and increased
irritability of the nervous system, resulting in tremors, confusion,
hallucinations and insomnia. Voclosporin showed significantly higher
levels of magnesium than tacrolimus, improving the overall safety
profile.
                                     Patients      Elevated      Magnesium
    Drug                            with NODM    Triglycerides   (6 months)
    Tacrolimus                        16.4%           39.2%     1.77 mmol
    Low dose voclosporin               1.6%(x)        17.5%(x)  1.98 mmol(xx)
    Mid dose voclosporin               5.7%           29.7%     1.95 mmol(xx)
    High dose voclosporin             17.7%           27.5%     1.89 mmol(xx)
    (x)  Significantly different from tacrolimus, p(less than)0.05
    (xx) Significantly different from tacrolimus, p(less than)0.005
Voclosporin also showed trends to a reduced incidence of insomnia
and tremors at the six month time point as compared to tacrolimus.
This reduced side effect burden is also clinically meaningful to
patients and their physicians.
                                                     Tremors
    Drug                                           (6 months)      Insomnia
    Tacrolimus                                        12.5%          14.0%
    Low dose voclosporin                               3.0%           7.1%
    Mid dose voclosporin                               3.1%          10.4%
    High dose voclosporin                              2.9%           6.9%
Kidney Function
In the evaluation of kidney function, there were no significant
differences noted between the voclosporin and tacrolimus groups.
Kidney function was well preserved in each of the three dose levels
of voclosporin relative to tacrolimus. Voclosporin did not meet one
of the secondary objectives, a 5% improvement in kidney function as
determined by iothalamate GFR.
                                  Iothalamate     Nankivell        Serum
                                      GFR            GFR        Creatinine
    Drug                            (mL/min)       (mL/min)   ((micro)mol/L)
    Tacrolimus                          65             69            120
    Low dose voclosporin                56             71            122
    Mid dose voclosporin                64             72            123
    High dose voclosporin               60             68            131
     Better kidney function is indicated by a higher GFR and a lower serum
     creatinine.
The results indicate that the dosage can be adjusted to maximize
efficacy without having deleterious effects on the kidney.
Dose response relationship
Analysis of the pharmacokinetic and pharmacodynamic data from
this trial suggests that an ideal dosing strategy is readily
identifiable with voclosporin. A wide therapeutic window which
optimizes both efficacy and safety has now been confirmed, allowing
transplant physicians and surgeons to individualize voclosporin
dosing for their patients.
"These positive results clearly demonstrate that voclosporin
offers significant clinical benefit. We believe that the efficacy and
enhanced safety profile of voclosporin compared to the market leader
tacrolimus gives us a product that offers significant benefit to
patients. These attributes also confirm voclosporin's commercial
potential in a market which is predicted to grow to more than CND$4
billion by 2010," stated Dr. Robert  Foster, Chairman and CEO of
Isotechnika Inc. "We look forward to advancing voclosporin into
pivotal phase 3 trials and moving one step closer to
commercialization."
Phase 2b Trial Design
PROMISE is a randomized, multicenter, open-label, concentration
controlled, dose ranging, safety study of voclosporin and tacrolimus
in de novo renal transplant patients. Patients received an initial
dose of 0.4, 0.6 and 0.8 mg/kg twice daily. All four arms of the
study were dosed to trough blood concentration levels as dictated by
the protocol. A total of 42 centers participated in the study, and
334 patients were enrolled. The primary endpoint was defined as
non-inferiority in biopsy proven acute rejection (BPAR) episodes in
patients receiving voclosporin for six months as compared to
tacrolimus control. Secondary endpoints examined clinical and
laboratory parameters such as kidney function, electrolytes,
neurological effects, NODM and lipid parameters.
About Isotechnika
Edmonton-based Isotechnika Inc. is an international
biopharmaceutical company focused on the discovery and development of
novel immunosuppressive therapeutics that are designed to offer
advantages over other currently available treatments. There is a
significant unmet medical need in the treatment of both solid organ
transplantation and autoimmune disease. It is estimated that the
market potential will exceed CND$4 billion annually in  sales for
calcineurin inhibitors such as voclosporin by 2010.
Voclosporin is a next generation calcineurin inhibitor, which
recently completed a Phase 2b North American trial for the prevention
of kidney rejection following transplantation. An extension to the
Phase 2b trial and a combined Phase 3 European/Canadian trial for the
treatment of moderate to severe psoriasis are ongoing. Our partner,
Lux Biosciences, is currently conducting three separate Phase 2/3
pivotal trials investigating voclosporin (referred to as LX211 by
Lux) for the treatment of uveitis. Voclosporin has also been approved
to enter First-in-Man trials as the drug utilized in the CINATRA(TM)
Drug Coated Coronary Stent system developed by the Company's partner,
Atrium Medical Corporation.
Isotechnika Inc. is a publicly traded company on the Toronto
Stock Exchange under the symbol "ISA". More information on
Isotechnika can be found at http://www.isotechnika.com.
Forward-Looking Statements
This press release may contain forward-looking statements. Such
forward-looking statements involve known and unknown risks,
uncertainties and other factors that may cause actual results, events
or developments to be materially different from any future results,
events or developments expressed or implied by such forward-looking
statements. Forward-looking statements, including the Company's
belief as to the potential of its products, the Company's
expectations regarding the issuance of additional patents and the
Company's ability to protect its intellectual property, involve known
and unknown risks and uncertainties, which could cause the Company's
actual results to differ materially from those in the forward-looking
statements. Such risks and uncertainties include, among others,
securing and maintaining corporate alliances, the need for additional
capital and the effect of capital market conditions and other factors
on capital availability, the ability to economically manufacture its
products, the potential of its products, the success and timely
completion of clinical studies and trials, the Company's ability to
successfully commercialize its products, competition, the ability of
the Company to defend its patents from infringement by third parties,
and the risk that the Company's patents may be subsequently shown to
be invalid or infringe the patents of others. Additional risks and
uncertainties relating to the Company and its business can be found
in the "Risk Factors" section of the Company's Annual Information
Form. These factors should be considered carefully and readers are
cautioned not to place undue reliance on such forward-looking
statements.
For further information: Dr. Robert Foster, Chairman & CEO,
Isotechnika Inc., Phone: +1-780-487-1600 Ext. 272, Fax:
+1-780-484-4105, Email:  rfoster@isotechnika.com; Stephanie
Gillis-Paulgaard, Director, Corporate Communications, Isotechnika
Inc., Phone: +1-780-909-4661, Email: 
sgillis-paulgaard@isotechnika.com

Contact:

For further information: Dr. Robert Foster, Chairman & CEO,
Isotechnika Inc., Phone: +1-780-487-1600 Ext. 272, Fax:
+1-780-484-4105, Email: rfoster@isotechnika.com; Stephanie
Gillis-Paulgaard, Director, Corporate Communications, Isotechnika
Inc., Phone: +1-780-909-4661, Email:
sgillis-paulgaard@isotechnika.com

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