Theralase® Provides Update on Phase II Bladder Cancer Clinical Study

Rhea-AI Summary

Theralase Technologies Inc. (TLTFF) announced an update on its Phase II Non-Muscle Invasive Bladder Cancer (NMIBC) Clinical Study, reporting treatment milestones for 35 patients, adding to the previous 3 from Phase Ib. Preliminary results show a 44.7% complete response rate at 90 days for 38 patients. Optimized treatments indicate improved results with 52.2% CR at 90 days for the optimized group. The study, targeting 100-125 patients, aims to evaluate efficacy and safety of the light-activated therapeutic TLD-1433.

Positive

• 44.7% complete response at 90 days from the overall 38 patients.
• 52.2% complete response in 23 optimized treatment patients at 90 days.
• Overall 60.5% total responders (CR + PR) at 90 days.

Negative

• 13.2% CR at 450 days reveals potential drop in efficacy over time.
• 7 serious adverse events reported, including one Grade 5.

TORONTO, April 05, 2022 (GLOBE NEWSWIRE) -- Theralase^® Technologies Inc. (“Theralase” or the “Company”) (TSXV: TLT) (OTCQB: TLTFF), a clinical stage pharmaceutical company focused on the research and development of light activated Photo Dynamic Compounds (“PDC”) ¹ and their associated drug formulations, intended for the safe and effective destruction of various cancers, bacteria and viruses, has provided an update on the Phase II Non-Muscle Invasive Bladder Cancer (“NMIBC“) Clinical Study (“Study II”).

As previously announced, Theralase^® successfully completed a Phase Ib NMIBC Clinical Study (“Study I”), which enrolled and provided the primary study treatment, at the therapeutic dose, for 3 patients. To date, Study II has enrolled and provided the primary study treatment for 35 patients, which when combined with the Study I data, leads to a total of 38 patients, who have received at a minimum, the primary study treatment.

Study II Clinical Study Data:

Assessment (Days)	Complete Response (“CR”) 2	Partial Response (“PR”) 3	Pending 4	CR (Evaluable Patients) 5	Total Responders (CR + PR) 6	Potential Responders (CR + PR + Pending) 7
90	44.7%	15.8%	10.5%	50.0%	60.5%	71.1%
180	31.6%	15.8%	28.9%	44.4%	47.4%	76.3%
270	23.7%	5.3%	42.1%	40.9%	28.9%	71.1%
360	13.2%	7.9%	47.4%	25.0%	21.1%	68.4%
450	13.2%	5.3%	47.4%	25.0%	18.4%	65.8%

On July 30, 2020, the Company optimized the Study II treatment, specifically:

a) Bladder volume calculation for administration of the study drug and study device volume
b) Study device treatment time

The Study II optimized treatment patients, who received either an optimized primary study treatment or optimized maintenance study treatment consisted of: 23 patients at 90 days, 26 patients at 180 days and 27 patients at each of 270, 360 and 450 days.

Study II Clinical Study Data (Optimized: Post August 1, 2020):

Assessment (Days)	Complete Response (“CR”)2	Partial Response (“PR”)3	Pending4	CR (Evaluable Patients)5	Total Responders (CR + PR)6	Potential Responders (CR + PR + Pending)7
90	52.2%	17.4%	13.0%	60.0%	69.6%	82.6%
180	22.2%	18.5%	40.7%	40.0%	42.3%	83.0%
270	14.8%	3.7%	59.3%	36.4%	18.5%	77.8%
360	3.7%	7.4%	66.7%	11.1%	11.1%	77.8%
450	3.7%	3.7%	66.7%	11.1%	7.4%	74.1%

Note: The interim analyses presented above, should be read and interpreted with caution, as the reported clinical data is early in its presentation. Study II is presently ongoing and new clinical data collected may or may not continue to support the current reported trends.

Study II Objectives:

• Primary - Efficacy (defined by CR) at any point in time.
• Secondary - Duration of CR (defined by duration of CR lasting a minimum 360 days post-initial CR).
• Tertiary - Safety measured by incidence and severity of Adverse Events ("AEs") grade 4 or higher that do not resolve within 450 days post primary study treatment. (Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Serious, Grade 4 = Life Threatening and Grade 5 = Death)
  

Performance to Objectives:

Primary:
For 38 patients enrolled and treated in Study II:
44.7% achieved CR at 90 days, with 50% achieving CR with evaluable patients and a potential of 71.1%, if all PR and Pending patients achieved CR

For 23 patients enrolled and treated in Study II (who received an optimized primary study treatment):
52.2% achieved CR at 90 days, with 60% achieving CR with evaluable patients and a potential of 82.6%, if all PR and Pending patients achieved CR

Secondary:
For 38 patients enrolled and treated in Study II:
13.2% achieved CR at 450 days, with 25% achieving CR with evaluable patients and a potential of 65.8%, if all PR and Pending patients achieved CR

For 27 patients enrolled and treated in Study II (who received an optimized primary or maintenance study treatment):
3.7% achieved CR at 450 days, with 11.1% achieving CR with evaluable patients and a potential of 74.1%, if all PR and Pending patients achieved CR

Tertiary:
For 38 patients enrolled and treated in Study II, there have been 7 Serious Adverse Events (“SAEs”) reported:

• 1 – Grade 2 (resolved within 1 day)
• 3 – Grade 3 (resolved within 5, 80 and 107 days, respectively)
• 2 – Grade 4 (resolved within 6 and 6 days, respectively)
• 1 – Grade 5 (not resolved))

Theralase^® believes all SAEs reported to date are unrelated to the Study Drug or Study Device, subject to final review and confirmation by the independent Data Safety Monitoring Board (“DSMB”).

Conclusion:

Study II has delivered significant clinical results to date for the primary, secondary and tertiary objectives.

Dr. Vera Madzarevic, Ph.D., Director of Clinical Development and Quality Assurance at Theralase^® stated, “From the 38 patients treated to date in Study II, those evaluable patients, have achieved 50.0% CR at 90 days and 25.0% have maintained this CR for at least 450 days, since primary study treatment. Additionally, total responders (CR +PR) at 90 days is 60.5% and 18.4% at 450 days; however, there is significant data still pending. This provides clinical support for achieving the primary and secondary objectives of Study II. The tertiary objective clinical data is promising, as only 7 SAEs were reported to date. Theralase^® believes these 7 SAEs are unrelated to the Study Drug or Study Device. In conclusion, it is encouraging to see, from the preliminary clinical data that the Company has accumulated to date, that if the trends continue, then Theralase^® is on track to achieving the primary, secondary and tertiary Study II objectives.”

Dr. Arkady Mandel M.D. Ph.D. D.Sc., Interim Chief Executive Officer and Chief Scientific Officer, Theralase^® stated, “I am encouraged by the clinical results to date, which demonstrate the potential to fill an unmet need for patients diagnosed with BCG-Unresponsive NMIBC. These patients are facing bladder removal and by delivering them a complete response with a durability lasting up to 15 months post primary study treatment, Theralase^® is providing them an opportunity to retain their bladder and the quality of life associated with it.”

Definitions:

¹ PDCs are light sensitive molecules that are able to produce highly volatile singlet oxygen and Reactive Oxygen Species (“ROS”), that can induce inactivation of cancer cells, bacteria or viruses through oxidative stress, when activated by light at a particular wavelength.

² Complete Response (“CR”) is defined according to the FDA Guideline “BCG-Unresponsive Nonmuscle Invasive Bladder Cancer: Developing Drugs and Biologics for Treatment Guidance for Industry” (U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (“CDER”) Center for Biologics Evaluation and Research (“CBER”) - February 2018):

“For single-arm trials of patients with BCG-Unresponsive disease using intravesical therapies without systemic toxicity, the FDA defines a Complete Response (“CR”) as at least one of the following:

• Negative cystoscopy and negative (including atypical) urine cytology
• Positive cystoscopy with biopsy-proven benign or low-grade NMIBC and negative cytology
• Negative cystoscopy with malignant urine cytology, if cancer is found in the upper tract or prostatic urethra and random bladder biopsies are negative”
  

³ Partial Response (“PR”) is defined as patients who display either positive cystoscopy and negative urine cytology or negative cystoscopy and positive urine cytology during an assessment visit. According to the FDA guidance, patients participating in Study II, who are currently diagnosed as PR, may be re-classified as CR, if the cystoscopy is positive, low grade NMIBC is detected and the urine cytology is negative or if urine cytology is positive, cystoscopy is negative and upper tract or prostatic urethra urothelial cell carcinoma is detected.

⁴ Pending is defined as patients, who have not been assessed at a specific time point; hence, their clinical data is currently awaiting assessment.

⁵ CR (Evaluable Patients) is defined as patients who have demonstrated CR with evaluable data; hence, excluding patients who have clinical data Pending.

⁶ Total Responders (CR + PR) is defined as patients who have demonstrated either a CR or PR.

⁷ Potential Responders (CR + PR + Pending) is defined as patients who have demonstrated a CR, PR or have clinical data Pending.

About Study II
Study II utilizes the therapeutic dose of TLD-1433 (0.70 mg/cm²) activated by the proprietary TLC-3200 medical laser system. Study II is focused on enrolling and treating approximately 100 to 125 BCG-Unresponsive NMIBC Carcinoma In-Situ (“CIS”) patients in up to 15 Clinical Study Sites (“CSS”) located in Canada and the United States.

About TLD-1433
TLD-1433 is a patented PDC with over 10 years of published peer reviewed preclinical research and is currently under investigation in Study II.

About Theralase^® Technologies Inc.
Theralase^® is a clinical stage pharmaceutical company dedicated to the research and development of light activated compounds and their associated drug formulations with a primary objective of efficacy and a secondary objective of safety in the destruction of various cancers, bacteria and viruses.

Additional information is available at www.theralase.com and www.sedar.com

Neither TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this release.

Forward Looking Statements

This news release contains "forward-looking statements" within the meaning of applicable Canadian securities laws. Such statements include, but are not limited to, statements regarding the Company's proposed development plans with respect to Photo Dynamic Compounds and their drug formulations. Forward looking statements may be identified by the use of the words "may, "should", "will", "anticipates", "believes", "plans", "expects", "estimate", "potential for" and similar expressions including statements related to the current expectations of Company's management for future research, development and commercialization of the Company’s Photo Dynamic Compounds and their drug formulations, including preclinical research, clinical studies and regulatory approvals.

These statements involve significant risks, uncertainties and assumptions; including, the ability of the Company to: adequately fund, and secure the requisite regulatory approvals to successfully complete a Phase II NMIBC clinical study in a timely fashion and implement its development plans. Other risks include: the ability of the Company to successfully commercialize its drug formulations, the risk that access to sufficient capital to fund the Company’s operations may not be available or may not be available on terms that are commercially favorable to the Company, the risk that the Company’s drug formulations may not be effective against the diseases tested in its clinical studies, the risk that the Company’s fails to comply with the term of license agreements with third parties and as a result loses the right to use key intellectual property in its business, the Company’s ability to protect its intellectual property, the timing and success of submission, acceptance and approval of regulatory filings, and the impacts of public health crises, such as COVID-19. Many of these factors that will determine actual results are beyond the Company's ability to control or predict.

Readers should not unduly rely on these forward- looking statements which are not a guarantee of future performance. There can be no assurance that forward looking statements will prove to be accurate as such forward looking statements involve known and unknown risks, uncertainties and other factors which may cause actual results or future events to differ materially from the forward-looking statements.

Although the forward-looking statements contained in the press release are based upon what management currently believes to be reasonable assumptions, the Company cannot assure prospective investors that actual results, performance or achievements will be consistent with these forward-looking statements.

All forward-looking statements are made as of the date hereof and are subject to change. Except as required by law, the Company assumes no obligation to update such statements.

For More Information:

1.866.THE.LASE (843.5273)
416.699.LASE (5273)
www.theralase.com

Kristina Hachey, CPA
Chief Financial Officer
khachey@theralase.com
416.699.LASE (5273) x 224 

FAQ

What are the latest results from Theralase Technologies' Phase II NMIBC study TLTFF?

The latest Phase II study results show a 44.7% complete response at 90 days for 38 patients. Optimized treatments indicate a 52.2% response rate for 23 patients.

What is the objective of Theralase's Phase II NMIBC study?

The primary objective is to evaluate the efficacy of TLD-1433, while secondary and tertiary objectives focus on the duration of complete response and safety evaluations.

How many patients are expected to participate in the NMIBC study?

The study aims to enroll approximately 100 to 125 patients diagnosed with BCG-Unresponsive NMIBC.

What are the reported adverse events in the NMIBC study by Theralase Technologies?

There have been 7 serious adverse events reported, including one Grade 5 event. Theralase believes these are unrelated to the study drug.

What is the significance of the results achieved in the Phase II NMIBC study?

The results indicate promising efficacy at 90 days with potential for sustained response, addressing an unmet need for patients facing bladder removal.