Frequently Asked Questions
Corporate Information
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 trades under the symbol ISA.
What is the Company’s current cash position?
At September 30, 2005 cash and short-term investments totalled $59.5 million, compared to $44.8 at June 30, 2005 and $60.2 million at December 31, 2004. On July 12, 2005 the Company closed a bought deal financing for net proceeds of $18.4 million by issuing 8.9 million Common Shares at $2.25 per share. Cash used for operations in the third quarter ended September 30, 2005 was $3.2 million and for the first nine months of the year ended September 30, 2005 was $18.7 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 September 30, 2005, the Company employs 80 people.
Voclosporin
What is the next step for pursuing voclosporin’s kidney transplant indication?
On January 5, 2006 the Company enrolled its first patient in a North American Phase IIb kidney transplant trial.
The trial will be performed at thirty-four centers across North America, including twenty-nine centers in the United States and five centers in Canada. A total of 332 de novo (newly transplanted) kidney transplant patients will be enrolled in this trial. Patients will be placed into one of four separate treatment groups; three different 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 will have their doses adjusted in order to achieve pre-defined blood levels of either voclosporin or tacrolimus. All patients will receive oral treatment of drug (voclosporin or tacrolimus) over a six month period along with other standard immunosuppressive therapies used following transplantation.
The primary endpoint of the trial is defined as non-inferiority in biopsy proven acute rejection (BPAR) episodes in patients receiving voclosporin for six months as compared to the tacrolimus control. Additionally, 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 that are typically seen with other calcineurin inhibitors such as cyclosporine and tacrolimus.
What stage of clinical trials is voclosporin currently in?
Voclosporin is currently being investigated in an extension protocol of a Phase III trial in Canada for the treatment of plaque psoriasis. The Company also enrolled its first patient in a North American Phase IIb kidney transplant trial on January 5, 2006.
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 is currently in an extension protocol of a Phase III clinical trial in Canada for the treatment of plaque psoriasis. The Company enrolled its first patient in a North American Phase IIb kidney transplant trial on January 4, 2006.
When did the Phase III psoriasis trial for voclosporin begin? When will it be finished?
The 24 week Canadian Phase III psoriasis trial for voclosporin is now complete. The extension protocol is ongoing with results expected in the fall of 2006.
What are the endpoints of the Phase III voclosporin trial?
Successful completion of the trial will be determined by the proportion of patients who achieve a 75% reduction in the psoriasis area and severity index (PASI). Secondary endpoints of the trial include maintenance of stable kidney function and assessment of quality of life.
What were the unblinded 24 week results for the Canadian Phase III psoriasis trial?
A Summary of the results is as follows:
- All primary and secondary efficacy endpoints were achieved at 24 weeks
- Efficacy endpoints were achieved with minimal side effects
- In the mid and low dose groups, continued improvement in PASI scores were observed from 12 to 24 weeks
- No clinically significant differences in mean serum creatinine and glomerular filtration rate (GFR) were observed amongst the four treatment groups at 24 weeks
In the high dose group, 48% of the patients achieved a PASI 75 score and 72% achieved a PASI 50 score. Furthermore, in the mid dose group 24% and 47% of the patients achieved PASI 75 and PASI 50 scores, respectively. Both the PASI 50 and PASI 75 scores were clinically significant (p<0.05) versus placebo. The mean percentage reduction in the PASI scores of the high dose group and the mid dose group were 62.5% and 44.0%, respectively.
Incidences of treatment-related adverse events in patients receiving voclosporin were similar to those receiving placebo. Additionally, there were no clinically significant changes noted in any of the parameters monitored including hypertension, cholesterol, triglycerides and infectious complications analyzed for the interim report. The highest mean change in serum creatinine at 12 weeks was 5% above baseline in the high dose (0.4 mg/kg twice daily) group. This mean percentage change is not clinically significant as it is within normal analytical and physiological variation. After 12 weeks of treatment, a total of five patients, (four in the high dose (4%) and one in the mid dose (1%)) were withdrawn from the trial due to a clinically significant effect on kidney function.
What other studies must Isotechnika do to commercialize voclosporin for psoriasis indications?
To commercialize voclosporin for the psoriasis indication, additional human Phase III pivotal trials are required. Planned future trials include a Phase III North American psoriasis trial and a Phase III psoriasis trial in Europe.
Additionally, a multiple dose QTc trial is required by the FDA to provide confirmation that there is no unanticipated significant QTc effect after multiple dose treatment of voclosporin. A single dose QTc trial was successfully completed in 2004 indicating no cardiac conduction changes at expected therapeutic doses.
The Company is also performing a two year rat carcinogenicity study, which commenced on January 25, 2005. In addition to this study, the Company is required to complete a carcinogenicity study in mice.
What were the results of the voclosporin Phase IIa 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 I trial results.
What is the next step for pursuing voclosporin’s kidney transplant indication?
On April 28, 2005, a No Objection Letter was received from Health Canada for the commencement of a Phase IIb kidney transplant trial. Subsequently, the Company received permission from the Food and Drug Administration of the United States to proceed with a Phase IIb kidney transplant trial for voclosporin.
The Company enrolled its first patient in the Phase IIB kidney transplant trial on January 4, 2006. The trial will be performed at thirty-four centers across North America, including twenty-nine centers in the United States and five centers in Canada. A total of 332 de novo (newly transplanted) kidney transplant patients will be enrolled in this trial. Patients will be placed into one of four separate treatment groups; three different 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 will have their doses adjusted in order to achieve pre-defined blood levels of either voclosporin or tacrolimus. All patients will receive oral treatment of drug (voclosporin or tacrolimus) over a six month period along with other standard immunosuppressive therapies used following transplantation.
The primary endpoint of the trial is defined as non-inferiority in biopsy proven acute rejection (BPAR) episodes in patients receiving voclosporin for six months as compared to the tacrolimus control. Additionally, 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 that are typically seen with other calcineurin inhibitors such as cyclosporine and tacrolimus.
Our Licensing Agreement with Atrium
On September 30, 2005, Isotechnika Inc. and Atrium Medical Corporation (“Atrium”) jointly announced the signing of an exclusive worldwide licensing agreement for the use of TAFA93 and voclosporin specifically with drug eluting devices for the non-systemic treatment of vascular, cardiovascular disorders, target vessel and tissue disorders.
What are the terms of the agreement with Atrium for the licensing agreement for voclosporin and TAFA93?
A summary of the terms of the agreement is as follows:
- Atrium will pay an upfront licensing fee of US$3,000,000.
- Atrium will pay milestone and royalty payments to Isotechnika upon approval of a medical device product which incorporates TAFA93, voclosporin or the combination of both drugs.
- Isotechnika is required to complete a Phase Ib trial for TAFA93.
- Atrium will conduct and be financially responsible for all development costs of the medical device product program.
- Isotechnika will manufacture and supply both drugs for use in clinical trials and post commercialization on a cost plus basis.
- Atrium will be solely responsible for marketing the Products which incorporate the TAFA93 and voclosporin compounds.
- The license provided is for the use of TAFA93 and voclosporin in conjunction with medical devices only. No rights are granted for the oral or topical administration of either TAFA93 or voclosporin in any indication.
Our Collaboration with Roche
When was the Roche Collaboration signed?
On April 9, 2002 the Company entered into a strategic collaboration with F. Hoffmann-La Roche and Hoffmann-La Roche Inc. (referred to as “Roche”) for the global co-development and commercialization of voclosporin. This agreement represented the largest Canadian early clinical trial drug development deal between a large pharmaceutical company and a biotech company.
How did Isotechnika’s collaboration with Roche change in 2004?
Under the original agreement, Roche had exclusive world wide rights to market both transplant and non-transplant indications of voclosporin.
By changing the Collaborative Agreement, Isotechnika regained the world-wide rights for all non-transplant indications, including psoriasis. Essentially, this means that the Company is free to market or license any of the non-transplant indications of voclosporin with a third party. The amended agreement transferred responsibility for all development costs of non-transplant indications to Isotechnika.
Roche still holds the exclusive world wide marketing rights to voclosporin for all transplant indications.
What are the new terms of the deal with Roche for voclosporin for transplant indications?
Under the new agreement, Isotechnika will pay all R&D costs until the completion of the Phase IIb renal transplant trial. Upon successful completion of this trial, Roche has the option to continue joint development in transplantation and is required to pay an exercise option fee of US$75 million.
Upon exercise of their option, Roche would contribute 70% of the development cost of voclosporin for transplantation indications and make milestone payments based on commencement, successful completion and NDA filing for the first three (3) transplant indications including kidney, liver and heart transplantations. The total amount of upfront and milestone payments have increased to $242 million US dollars from $215 million US dollars under the original agreement.
Upon commercialization, there is no change to the royalty structure from the original agreement.