Theralase Discovers New Mechanism of Action of Lead Drug

Theralase(R) Has Discovered a New Mechanism of Action in Its War on Cancer; Specifically, Ruvidar's(TM) Ability to Inhibit DeUbiquitinating Enzymes, an Important Class of Enzymes Which Have Been Linked to Numerous Cancers and Neurogenerative Diseases

Toronto, Ontario--(Newsfile Corp. - April 28, 2025) - Theralase® Technologies Inc. (TSXV: TLT) (OTCQB: TLTFF) ("Theralase®" or the "Company"), a clinical stage pharmaceutical company dedicated to the research and development of light, radiation, sound and/or drug-activated small molecules and their formulations, intended for the safe and effective destruction of various cancers, bacteria and viruses, is pleased to announce that Ruvidar^TM has recently been proven preclinically to be an effective inhibitor of DeUbiquitinating Enzymes ("DUBs"), an important class of enzymes which have been linked to numerous cancers and neurogenerative diseases.

DUBs cause cellular damage by removing ubiquitin or ubiquitin-like molecules from target proteins.

Ubiquitin is a small protein found in all eukaryotic cells (animals, plants and humans), which plays a crucial role in regulating various cellular processes, such as: gene expression, DNA repair, cytokine signaling, cell metabolism, cell cycle and cell death. It functions primarily through ubiquitination, a process where ubiquitin is conjugated to target proteins, marking them for degradation or altering their activity.

Altered DUBs activity is associated with multitudes of pathologies, including cancer; therefore, DUBs represent novel candidates for target-directed drug development.¹

Drug resistance to chemotherapy and molecularly targeted therapies are an ongoing challenge in cancer treatments. The underlying mechanisms of resistance to cytotoxic chemotherapeutics and to drugs that target a specific molecule are not understood completely. In recent years, emerging evidence has frequently suggested that the dysregulation of DUBs plays important roles in the development of drug resistance; hence, DUBs enable cancer cells to escape cell death and survive when exposed to a variety of anti-cancer drugs. Therefore, there exists the potential application of utilizing DUBs inhibitors in combinational therapies to overcome drug resistance.²

Targeting DUBs with inhibitors like Ruvidar™ is a very promising strategy to overcome drug resistance.

In previous Theralase® research, it was demonstrated that Ruvidar™ induces oxidative stress in cells through the production of Reactive Oxygen Species ("ROS").

In the latest research, we have investigated the effects of Ruvidar™ on DUBs activity and have demonstrated that Ruvidar™ inhibits DUBs activity in a dose-dependent manner.

This direct inhibition of DUBs, coupled with the known production of ROS by Ruvidar™, are an exciting new combination of the mechanisms of action of the effects that Ruvidar™ has on cancer cells, leading to a significant reduction in cancer cell growth.

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As shown in the figure above, increasing the amount of Ruvidar™ in cells directly correlates with a reduction in DUBs activity, with 100 µM of Ruvidar™ leading to almost no DUBs activity.

Dr. Mark Roufaiel, Research Scientist, Theralase® stated, "Our latest research provides compelling evidence that Ruvidar^TM not only induces oxidative stress through the production of ROS to destroy cancer cells, but also directly inhibits DUBs activity-a key host mechanism exploited by the cancer cell to evade immune defenses. This dual mechanism positions Ruvidar™ as a promising therapeutic candidate, particularly against cancers, where traditional chemotherapeutics demonstrate limited effectiveness."

Arkady Mandel, M.D., Ph.D., D.Sc., Chief Scientific Officer, Theralase® stated, "With the increasing prevalence of chemoradiotherapy resistant cancers, Ruvidar™, as an effective DUBs inhibitor, may be indispensable clinically to be used as a combinational therapy with various chemotherapy drugs and/or radiotherapy to provide a safe and effective treatment against various forms of chemoradiotherapy resistant cancers. The discovery of Ruvidar's™ effectiveness against DUBs is a notable milestone in the development of Theralase®'s small molecule program and can be used for treating cancer, but could be expanded far beyond this to the treatment of age associated medical conditions, various neurodegenerative diseases, such as Alzheimer's, Parkinson's and Multiple Sclerosis, as well as to effectively combat various infectious diseases".

Roger DuMoulin-White, B.Sc., P.Eng., Pro.Dir., President and Chief Executive Officer, Theralase® stated, "According to recent peer-reviewed research, reducing DUBs plays a very important role in the war against cancer and its innate ability to build up drug resistance. This latest research reinforces an additional mechanism of action beyond direct cancer destruction and indirect immune stimulation, stripping away one of cancer's final defence mechanisms. As Theralase® pursues clinical development of Ruvidar™ for numerous cancers, such as brain and lung cancer, I look forward to reporting out on the clinical safety and efficacy of these programs."

References:
¹ Farshi P et al. Deubiquitinases (DUBs) and DUB inhibitors: a patent review. Expert Opin Ther Pat. 2015;25(10):1191-1208.
² Fujing Ge et al. Deubiquitinating enzymes: Promising targets for drug resistance, Drug Discovery Today. Volume 27. Issue 9. 2022. Pages 2603-2613.

About Theralase® Technologies Inc.:
Theralase® is a clinical stage pharmaceutical company dedicated to the research and development of light, radiation, sound and/or drug-activated small molecule compounds, their associated drug formulations and the light systems that activate them, 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 theralase.com and www.sedarplus.ca

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 ("FLS") 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 small molecules and their drug formulations. FLS 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 the Company's management regarding future research, development and commercialization of the Company's small molecules; their drug formulations; preclinical research; clinical studies and regulatory approvals.

These statements involve significant risks, uncertainties and assumptions; including, the ability of the Company to fund and secure the regulatory approvals to successfully complete various clinical studies in a timely fashion and implement its development plans. Other risks include: the ability of the Company to successfully commercialize its small molecule and drug formulations; the risk that access to sufficient capital to fund the Company's operations may not be available on terms that are commercially favorable to the Company or at all; the risk that the Company's small molecule and drug formulations may not be effective against the diseases tested in its clinical studies; the risk that the Company fails to comply with the terms 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. 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 FLS, which are not a guarantee of future performance. There can be no assurance that FLS will prove to be accurate as such FLS involve known and unknown risks, uncertainties and other factors which may cause actual results or future events to differ materially from the FLS.

Although the FLS 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 FLS.

All FLS 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 FLS.

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