Mr. Roger DuMoulin-White reports

THERALASE DEMONSTRATES THAT X-RAY-ACTIVATED RUTHERRIN IS SIGNIFICANTLY MORE EFFECTIVE THAN RADIATION ALONE IN THE DESTRUCTION OF MUSCLE INVASIVE BLADDER CANCER

Theralase Technologies Inc. has presented its latest preclinical data demonstrating that X-ray-activated Rutherrin is effective in the destruction of muscle invasive bladder cancer.

In the MIBC preclinical models conducted by the Theralase research team, Rutherrin demonstrated an ability to significantly enhance the efficacy of radiation therapy in the destruction of MIBC, supporting its potential as an effective drug for this devastating condition.

Approximately 25 per cent of the 83,000-plus new bladder cancer cases diagnosed annually in the United States and 13,300-plus cases in Canada are MIBC. MIBC carries a significant risk of death that has not changed in decades.

The standard of care for MIBC is currently cisplatin-based neoadjuvant chemotherapy (preoperative) followed by radical cystectomy (bladder removal). In patients who undergo RC, systemic recurrence rates vary by stage, ranging from 20 per cent to 70 per cent.

As a bladder preservation option, trimodal therapy, composed of maximal transurethral resection of the bladder tumour, followed by radiation and chemotherapy, has become increasingly popular in recent years; however, patients must be appropriately selected.

Based on the latest preclinical data, Theralase is planning to conduct a phase 0/1/2 adaptive clinical study with radiation-activated Rutherrin, with or without chemotherapy and/or immunotherapy, subject to regulatory approval, for patients diagnosed with MIBC to provide an alternative treatment option versus RC or TMT.

With in vitro experiments using mouse MIBC cells (MBT-2), Rutherrin combined with 2.5 Gray X-ray radiation resulted in significantly greater cell death compared with radiation alone.

These results indicate that Rutherrin enhances radiation-induced cytotoxicity, supporting its potential as a radiosensitizer in the destruction of MIBC.

MBT-2 cells were used to establish an orthotopic MIBC model in mice, by surgically injecting the cells directly into the muscle layer of the mouse's bladder, leading to tumour growth and invasion of the muscle layer. In this model, the tumour grew into the bladder lumen, pushing against the inner urothelial layer, resulting in a reduction of the volume available for urine storage. If left untreated, the tumour would continue to grow until the bladder was completely blocked, rendering it inoperable and reaching the humane end point.

After systemic Rutherrin was administered intravenously to mice with MBT-2 tumours, tissue analysis showed that tumour sites had approximately four times higher Rutherrin levels than normal bladder, demonstrating tumour-selective uptake and a favourable therapeutic index (drug in cancer cells versus healthy cells).

In further research, Theralase is conducting a continuing in vivo MIBC study assessing the use of repeatable, intravenous Rutherrin administration, in combination with fractionated radiation therapy (total cumulative dose of 25 Gray). At day 35 in this study, all mice in the Rutherrin plus radiation group survived and showed complete tumour clearance; however, in the radiation alone, group mice exhibited persistent and larger tumour volumes, with 50 per cent of the mice reaching their humane end point posttreatment, with the other 50 per cent displaying steady growth in their tumours.

Mark Roufaiel, PhD, research scientist at Theralase, commented: "These preclinical findings demonstrate that Rutherrin selectively accumulates in MIBC tumours versus health bladder tissue and significantly enhanced the therapeutic effect of radiation. Most importantly, we observed complete tumour clearance in X-ray-activated Rutherrin-treated animals even under low radiation dosing conditions. This supports the potential of Rutherrin to improve radiation response and expand treatment options for patients with aggressive MIBC."

Arkady Mandel, MD, PhD, DSc, chief scientific officer, Theralase, stated: "Treatment options for MIBC patients are limited to cisplatin-based chemotherapy before RC or TMT. Preclinical data collected supports the clinical opportunity of employing X-ray-activated Rutherrin in the treatment of difficult-to-treat cancers such as glioblastoma multiforme, non-small-cell lung cancer, as previously reported, and now based on the recent data, MIBC. In preclinical studies, mice treated with radiation alone did not survive or continued to show detectable cancer with rapid tumour progression whereas mice treated with a combination of Rutherrin and radiation therapy showed no detectable cancer. These results will hopefully lay the groundwork for new therapeutic approaches for patients faced with these challenging diseases."

Roger DuMoulin-White, BSc, PEng, ProDir, president, chief executive officer and chairman of the board of Theralase, added: "The combination of selective tumour uptake by Rutherrin, demonstrated X-ray enhancement in vitro, accelerated tumour regression and complete tumour destruction in vivo at low radiation doses collectively supports the executive decision by Theralase to pursue clinical development of Rutherrin, as a radiation sensitizer in patients diagnosed with GBM, NSCLC and MIBC, subject to regulatory approval."

About Theralase Technologies Inc.

Theralase is a clinical-stage pharmaceutical company dedicated to the research and development of energy-activated small molecules for the safe and effective destruction of cancer, bacteria and viruses.

We seek Safe Harbor.