Jerusalem, Israel — BioCancell Therapeutics, Inc. (TASE:BICL) announced today the results of the obligatory part of the Phase I/IIa clinical trial it is funding in superficial bladder cancer. The results confirm success in achieving the objectives set for the Trial.
The Trial took place at two medical centers in Israel under the supervision of the Israeli Ministry of Health and in accordance with principles agreed upon with the FDA. The Trial was designed to determine the optimal dose and assess the safety and preliminary efficacy of BC-819 complemented with PEI (a transfection enhancer) given as intravesical infusions into the bladder of patients with superficial bladder cancer expressing the H19 gene, who had previously failed at least one standard treatment type. In the obligatory part of the Trial each patient received six weekly treatments with BC-819 whereas in the elective part of the Trial patients responding well to the treatment were offered up to nine additional monthly maintenance treatments.
Eighteen patients were enrolled in the Trial and split into five groups, with each group receiving a higher dosage than the previous. Escalating doses consisted of 2, 4, 6, 12 and 20mg of BC-819. All patients had failed at least one standard treatment type, with a third failing at least two. The mean number of previous tumor recurrences after treatment in patients entering the Trial was 5.
The results can be summarized as follows:
No Serious Adverse Events relating to the treatment were detected at any dose given. This is of critical importance, as it is the side effects of current treatments that cause many patients to abandon therapy, resulting in sub-optimal healing.
There was no dose-limiting toxicity at any dose given, so the optimal dose to be used in Phase II is 20mg, the maximum dose which was administered to patients in Phase I/IIa.
At the beginning of treatment, all tumors except one (measuring 0.5-1.0 cm in diameter) were surgically removed from the patient’s bladder. The remaining tumor was left as a marker to observe the effect of BC-819, despite the fact that the standard of treatment does not involve the leaving of a tumor marker.
The primary efficacy is categorized by tumor recurrence, tumor marker ablation and disease progression. It is recorded for all patients – including those not receiving the optimal dose.
In total, 72% of patients responded to treatment. The preliminary evaluation of the efficacy of BC-819 suggests that it has the ability to cause tumor ablation and regression at doses that are well tolerated.
Based on these positive results, BioCancell plans to begin Phase IIb in the fourth quarter of 2007. The aim of the phase will be testing the efficacy and safety of BC-819 at a dose of 20mg. The treatment of 33 patients will take place in approximately 6 medical centers in Israel and one in the U.S., pursuant to an IND approval from the FDA.
According to the American Cancer Society, urinary bladder cancer has the fourth highest incidence rate of all types, accounting for approximately 5% of all cancer cases. There are about 67,160 cases of superficial bladder cancer in the United States alone each year, with an annual mortality of 13,750 cases and prevalence of 600,000. Three quarters of patients are male, with 1 in 28 American men expected to develop bladder cancer in their lifetime. Some $1.9 billion is spent in the U.S. on treating bladder cancer annually.
Bladder cancer is a disease with a very high level of recurrence. Patients participating in the Trial, for example, had suffered from recurrence of bladder cancer an average of five times before enrolling in the Trial.
Current Standard of Treatment
Standard treatments for superficial bladder cancer include Bacillus Calmette-Guerin (BCG) and Mitomycin C, combined with surgery.
BCG is an inactivated form of the bacterium Mycobacterium tuberculosis. BCG has resulted in tumor regression in about 50% of treated patients with papillary tumors, and about 70% of those with CIS (carcinoma in situ). The most common side effect is dysuria (burning with urinating), but others include fever, malaise and nausea.
Mitomycin C is a chemotherapy drug, used to treat mainly bladder and rectal cancers. It works by sticking the DNA of cells together so that they can never come apart again, meaning that the cell cannot reproduce itself. Mitomycin C is usually given as a course of several cycles of treatment. The most common side effect is fatigue (for up to a year), but others include increased risk of infections, shortness of breath, bruising, loss of appetite, affected liver and kidney function, skin rash, sore mouth, diarrhea and loss of fertility.
Even where standard treatments prove therapeutically effective, they are characterized by severe adverse events often leading to patients abandoning treatment, resulting in sub-optimal healing. The Trial is being performed in patients who have failed the standard treatment.
BioCancell’s Technology – Patient-Oriented, Targeted Therapy
BioCancell’s technology is both Personal and Targeted. The approach is based on the identification of particular genes that are highly expressed only in tumors (“Target Genes”). The regulatory sequences of these Target Genes are used to drive the expression of a toxin gene exclusively within tumor cells, enabling targeted tumor-cell destruction, leaving normal cells intact. In effect, the plasmid acts as “smart bombs”, activated only inside their targets thus destroying only the cancerous cells, while leaving healthy cells intact.
The patient’s eligibility for the treatment is determined by analyzing the patient’s tumor for the expression of the specific Target Genes. The diagnosis of the expression of the Target Genes are, therefore, a prerequisite for treatment and is made possible through the Company’s proprietary diagnostic technology that enables detection of even a single malignant cell. Only those patients with high expression levels of the Target Genes in their tumor are eligible for treatment with high confidence of success.
The Company has designated two genes as Target Genes – H19 and IGF2.
Discovered by Professor Avraham Hochberg in humans, H19 is an oncofetal gene that encodes RNA (with no protein product) that is expressed at high levels in over 30 types of human cancer tissues, while existing at a nearly undetectable level in the surrounding normal tissues, thus making it an optimal weapon in the fight against cancer.
The gene is expressed abundantly in the human placenta and in several embryonic tissues, but is repressed post-natally and only re-expressed with the appearance of cancer, within cancer cells. Studies show that H19 fulfills an important role in the process of tumorigenesis, and it is thought that the gene enables tumor cells to survive and proliferate under stress conditions.
BC-819 is BioCancell’s leading product. It is a plasmid in which H19 regulatory sequences drive the expression of Diphtheria Toxin A gene. Besides the treatment of bladder cancer, BC-819 is in the process of being evaluated as treatment for liver, pancreatic and ovarian cancer and has shown efficacy in pre-clinical studies as well as in compassionate use.
BioCancell Therapeutics Inc. is a biopharmaceuticals corporation specializing in the development of Patient-Oriented, Targeted Therapy for the treatment of numerous types of cancer. The Company’s proprietary technology constitutes a novel paradigm for the targeted destruction of cancer cells, with no effect on normal surrounding tissue and no observed side effects, allowing for long-term, safe treatment and prevention of cancer.
BioCancell was co-founded in 2004 by Professor Avraham Hochberg, Professor of Molecular Biology at the Hebrew University of Jerusalem, based on technology developed by him over the past 15 years.
In 2006, BioCancell successfully completed a private round of funding and an initial public offering totaling $8.5 million. Its securities are traded on the Tel Aviv Stock Exchange, with the major stockholders being Clal Biotechnology Industries, a member of the IDB group of companies, and Prof. Hochberg.
This press release contains “forward-looking” statements, including statements with respect to the further development and potential safety and efficacy of BC-819, in the treatment of superficial bladder cancer and BioCancell’s development strategy. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. There are a number of important factors that could cause the results of BioCancell to differ materially from those indicated by these forward-looking statements, including, among others, the risk that the U.S. Food and Drug Administration may require changes to the protocols and informed consents for clinical trials of BC-819, which changes may have a material adverse effect on the timing of, and BioCancell’s ability to conduct, those clinical trials, risks related to the clinical advancement of its BC-819 plasmid, including, but not limited, to the risk that clinical trials for this product candidate may not demonstrate safety and efficacy sufficient to obtain the requisite regulatory approvals or to result in a marketable product and risks related to the potential for others to develop products containing or based on BC-819. BioCancell does not undertake any obligation to update forward-looking statements.