Frequently Asked Questions
When was Isotechnika founded?
The Company was incorporated in 1993 and was listed on the Alberta Stock Exchange in 1996.
Where is the stock listed?
Isotechnika’s common shares are currently listed on the Toronto Stock Exchange (TSX) and trade under the symbol ISA.
What is the Company's current cash position?
At December 31, 2007, cash, cash equivalents and short-term investments totalled $32.0 million.
What is the vision for Isotechnika?
Isotechnika is focused on the discovery and development of novel therapeutic immunosuppressive drug candidates.
How many people are employed by Isotechnika?
As of December 31, 2007, the Company employs 76 people.
Voclosporin
What is voclosporin?
Voclosporin is an immunosuppressive drug in the class of calcineurin inhibitors.
What are the potential therapeutic uses for voclosporin?
Voclosporin is a multi-platform drug that could potentially be used to treat moderate to severe psoriasis, and has the potential for use in preventing organ rejection in transplantation.
What stage of clinical trials is voclosporin currently in?
Voclosporin recently completed a Phase 2b North American trial for the prevention of kidney rejection following transplantation in December 2007. An extension to the Phase 2b trial, and a combined Phase 3 European/Canadian trial for the treatment of moderate to severe psoriasis, is 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.
What is the status of the combined Phase 3 European/Canadian (ESSENCE) trial?
On March 31, 2008, the Company announced that an independent data monitoring committee (DMC) met and reviewed the interim data from the ongoing blinded Phase 3 psoriasis trial. The review included 24-week data from approximately 50% of the patients enrolled in the trial. Based on their review of the safety and efficacy data, the DMC did not raise any concerns that would require a change to the original study trial.
The first patient was enrolled in the ESSENCE trial on December 3, 2006. On July 20, 2007, the Company completed patient recruitment at 642 patients. The patient population is composed of 295 patients from Germany, 116 from Poland and 231 from Canada. The trial is currently being performed at a total of 50 centers.
The ESSENCE trial is being conducted as a randomized, orally administered placebo and cyclosporine controlled study with patients receiving voclosporin (0.4mg/kg twice daily), patients receiving cyclosporine (1.5 mg/kg twice daily) and patients receiving placebo in a 3:1:1 ratio for 24 weeks. Patients enrolled in the placebo group will be converted to the voclosporin arm following the first 12 weeks of treatment.
Upon the Company receiving regulatory approval for an extension to this trial, patients who had not yet finished the 24 week portion of the trial were given the opportunity to remain on therapy for an additional 36 weeks - making the total length of treatment 60 weeks for those patients.
Successful completion of the trial will be determined by the primary endpoint of superiority in the proportion of patients achieving a score of "clear" or "almost clear" in the Static Physician's Global Assessment (SPGA) score at 12 weeks in the voclosporin treatment group compared to placebo control. Secondary endpoints include, amongst others, non-inferiority of voclosporin compared to the cyclosporine control arm in the proportion of patients achieving a score of "clear" or "almost clear" in the SPGA score at 12 weeks and a 75% reduction in the PASI score.
What were the unblinded 60 week results for the Canadian Phase 3 psoriasis trial?
On October 5, 2006, Isotechnika announced final safety and efficacy results (60 week data) from the Canadian Phase 3 psoriasis trial. Patients received continuous treatment with voclosporin for a total of 60 weeks. Over the course of the 24-week Phase 3 trial, patients exhibited a 60% mean improvement in Psoriasis Area and Severity Index (PASI) scores. After an additional 36 weeks of treatment, there was a 54% mean improvement in PASI scores indicating continued therapeutic benefit. This beneficial effect was still observed twelve weeks after discontinuing voclosporin treatment; mean PASI scores remained at 35% below pre-treatment scores.
Subsequent to 60 weeks of continuous treatment, there were no clinically significant changes in kidney function, cholesterol, triglycerides, new onset diabetes, infectious complications, or other laboratory parameters. This supports the long term safety of voclosporin.
What other studies must Isotechnika complete to commercialize voclosporin for psoriasis?
The Company, to meet FDA guidelines, was required to perform a multiple dose QTc study to confirm that there are no unanticipated, significant QTc effects associated with repeated dose treatment of voclosporin. As psoriasis is not considered a life threatening disease, safety is of paramount importance. A single dose QTc trial was successfully conducted by the Company in 2004 indicating no cardiac conduction abnormalities were detected at therapeutic doses of voclosporin. The required multiple dose QTc trial commenced in September, 2005. The trial was delayed by approximately one month when a cohort of trial subjects had to be replaced due to one of the subjects being inadvertently admitted to the trial with pre-existing tuberculosis by the CRO (SFBC Anapharm, a division of SFBC International, Inc.). The diagnosed tuberculosis, therefore, was not drug-eluted. The last patient, last visit portion of the trial was completed on January 24, 2006. The draft results from this trial, received on April 25, 2006, indicate that repeated oral dosing of voclosporin at 1.5 mg/kg bid for 13 doses is not associated with QTc elevation. This result meets the regulatory criteria for a negative QTc effect with voclosporin. The final results received by the Company in June, 2006 reflected no differences from those indicated in the draft report noted above.
For regulatory purposes, the Company is required to perform rat and mouse carcinogenicity studies where voclosporin is repeatedly administered over a period of two years. Carcinogenicity studies are required by the FDA and other regulatory authorities, and are a critical part of the package submitted for marketing approval. Carcinogenicity studies are performed by administering a range of doses of a drug, including a dose considerably higher than the anticipated clinical dose, for a period of two years. This timeframe is equivalent to administering the drug over a lifetime in humans.
The FDA approved the protocol for the two year rat study in November 2004, and the study commenced on January 25, 2005. The active dosing portion of the rat study was completed in December 2006. The CRO performing the study is in the process of analyzing the data and preparing the required study report. The Company received the final draft report in November 2007. Voclosporin did not exhibit any carcinogenicity up to the highest doses tested in male and female rats over a two year period.
Commencing in the third quarter of 2005, the Company conducted dose-range finding studies in mice to determine the appropriate dosing for the two year mouse study. The information obtained from the dose-range studies was submitted to the FDA. The Company received FDA approval for the protocol for the two year mouse study in February 2006 and the study commenced in March 2006. The active dosing portion of the study was completed in December 2007 with receipt of the final report scheduled for late 2008.
What were the results of the voclosporin Phase 2a kidney transplantation trial?
The primary endpoint of the trial was to demonstrate that stable kidney transplant patients receiving mix-voclosporin experienced no negative change in kidney function when compared to patients on cyclosporine (Neoral®). The secondary endpoint of the study was to measure the pharmacodynamics and pharmacokinetics of mix-voclosporin in renal transplant patients. All of these endpoints were achieved.
Patients receiving mix-voclosporin showed no further deterioration in kidney function when compared to those receiving cyclosporine. In this trial renal transplant patients switched from cyclosporine to mix-voclosporin in a safe and effective manner. Additionally, no rejection episodes occurred in patients receiving mix-voclosporin.
Drug concentrations of cyclosporine in blood were three times higher than that of mix-voclosporin. However, immunosuppressive activity of both drugs, as measured by calcineurin inhibition, was the same. This indicated that mix-voclosporin was at least three times more potent than cyclosporine which was consistent with all pre-clinical and Phase 1 trial results.
What is the status of voclosporin for transplantation?
A randomized, open-label trial is currently ongoing. This involves the recruitment of 334 de novo (newly transplanted) kidney patients from forty-two clinical trial sites across North America, including thirty-eight centers in the United States and four centers in Canada. Patient enrolment was completed on June 26, 2007.
Patients were placed into one of four separate treatment groups; three diferrent dose groups of voclosporin (0.4 mg/kg, 0.6 mg/kg and 0.8 mg/kg twice daily) compared with the fourth group, a tacrolimus (0.05 mg/kg twice daily) control arm. Patients in all four treatment groups had their doses adjusted in order to achieve pre-defined blood levels of either voclosporin or tacrolimus. All patients received oral treatment of the drug (voclosporin or tacrolimus) over a six month period, along with other standard immunosuppressive therapies used following transplantation.
On January 3, 2008, the Company announced that the last patient enrolled completed the six month trial. On June 7, 2007, and August 2, 2007, the Company announced that it had received permission from Health Canada and the Food and Drug Administration (USA), respectively, to allow patients to remain on voclosporin until the drug is commercially available.
The primary endpoint of the trial is defined as non-inferiority in biopsy proven acute rejection (BPAR) episodes with patients receiving voclosporin for six months as compared to tacrolimus. Additionally, patient’s kidney function and other laboratory parameters such as hypertension, hyperlipidemia and new onset diabetes mellitus will be monitored for the duration of the trial. The overall goal of the trial is to find the most appropriate dose that will result in efficacy (lack of rejection) with minimal side effects. The use of the other two calcineurin inhibitors, cyclosporine and tacrolimus, are often associated with significant safety concerns.
OUR AGREEMENT WITH LUX BIOSCIENCES, INC
On May 24, 2006, the Company signed an agreement with Lux granting them worldwide rights to develop and commercialize voclosporin for the treatment and prophylaxis of all ophthalmic diseases.
Under the terms of the agreement, Lux will make upfront and milestone payments to Isotechnika. Assuming all development milestones are achieved, the amount of this deal will be US$32.7 million. Isotechnika received an upfront payment of $3.32 million (US$3.0 million) upon signing the agreement. Lux will also pay Isotechnika royalties based on a percentage of net sales. Isotechnika is the sole supplier of voclosporin for clinical trial and commercial purposes.
Lux will be responsible for pre-clinical and clinical development, registration and marketing of voclosporin for all ophthalmic indications.
OUR OPTION AGREEMENT WITH CELLGATE INC.
On April 24, 2006, the Company signed an option agreement with Cellgate Inc. (Cellgate) of Redwood City, California. This agreement allowed Isotechnika the option to obtain an exclusive license to develop and commercialize conjugates consisting of Cellgate's patented transporter technology for the topical delivery of voclosporin in patients suffering from mild to moderate psoriasis.
The development of an effective topically administered voclosporin product would potentially allow the Company to expand the use of voclosporin into the milder cases of psoriasis where topical, rather than systemic administration, is warranted.
Under the terms of the agreement, Cellgate is to perform studies to evaluate the feasibility of using their technology to topically deliver voclosporin. Currently Isotechnika is waiting for final study reports from the nonclinical studies that were conducted under the terms of the agreement. Upon receipt of these final study reports the Company will evaluate the potential of this technology and make a decision whether or not to enter into a license agreement with Cellgate.
OUR LICENSING AGREEMENT WITH ATRIUM MEDICAL CORPORATION
On September 29, 2005, the Company signed an exclusive worldwide licensing agreement with Atrium for the use of TAFA93 and voclosporin with drug-eluting medical devices. These devices deliver the drug locally to treat cardiovascular disorders and assist in the soft tissue repair (e.g., stents and surgical meshes, respectively). As such, Atrium's implantable product line utilizes the non-systemic applications of these two drugs. The company received a licensing fee of $3,490,000 (US$3,000,000) and will receive further milestone and royalty payments once the drug-eluting devices are commercialized. Isotechnika will supply the drug compounds to Atrium. The Company may discontinue the supply of TAFA93 upon six months prior written notice to Atrium. In such event Atrium may, at its sole expense, either manufacture its own requirements or purchase its requirements from a third party. Atrium will conduct and be financially responsible for all clinical development costs of the medical device product programs.
On August 29, 2007, the License and Supply Agreement dated September 29, 2005 with Atrium was amended to establish a Joint Steering Committee (JSC). The JSC has equal membership from Isotechnika and Atrium and was formed to ensure that Atrium's development programs utilizing voclosporin and TAFA93 are conducted pursuant to the terms of the agreement.
OUR COLLABORATION WITH ROCHE
On April 19, 2004, Isotechnika and Roche amended the original Collaboration Agreement which was signed on April 9, 2002, whereby Isotechnika reacquired the world-wide rights for all non-transplant indications of voclosporin, including psoriasis. Isotechnika can develop any of the non-transplant indications of voclosporin internally and is also free to market and license any of the non-transplant indications of voclosporin with any third party.
Under the amended terms of the Collaboration Agreement, Roche has an option to develop and commercialize voclosporin for transplant indications up to the completion of the six month Phase 2b kidney transplant trial. Upon receipt of the final Phase 2b kidney transplant trial report, expected in May 2008, Roche will have 90 days to exercise its option. To exercise this option, Roche will pay an option exercise fee of US$75,000,000, make future milestone payments, and be responsible for 70% of future shared development costs of voclosporin for transplant indications. Upon commercialization there is no change to the royalty structure from the original agreement for transplant indications. There is no assurance that Roche will exercise their option upon receipt of the final Phase 2b kidney transplant trial report, even if the Company deems the trial to be successful.