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NEW SCIENTIFIC PUBLICATION SHOWS LB-100, LIXTE’S LEAD CLINICAL COMPOUND, CAN FORCE CANCER CELLS TO GIVE UP THEIR CANCER-CAUSING PROPERTIES

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LIXTE Biotechnology Holdings, Inc. announces a groundbreaking discovery that its lead clinical compound, LB-100, can force cancer cells to become less cancerous, opening up a new treatment strategy. The pre-clinical data published in Cancer Discovery shows that LB-100, when combined with a WEE1 kinase inhibitor, is highly effective in killing colon cancer cells. The unique feature of LB-100 is its ability to hyper-activate cancer signals, leading to cancer cells becoming less malignant and unable to form tumors. This 'tumor suppressive drug resistance' concept could revolutionize cancer treatment.
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The pre-clinical findings regarding LB-100 present a fascinating shift in the approach to cancer therapy. Traditional treatments often aim to inhibit oncogenic signaling, but here we see a paradigm where pushing these signals into overdrive, paradoxically, leads to a therapeutic effect. This hyper-activation, particularly when coupled with a WEE1 kinase inhibitor, appears to induce a state of 'tumor suppressive drug resistance.' Essentially, cancer cells are left with two choices: die or lose their malignancy. The latter is an intriguing concept, as it suggests a form of 'evolutionary therapy' where the pressure exerted by the drug forces cancer cells to adapt in a less harmful direction.

From a clinical perspective, this could represent a significant advancement in cancer treatment. The ability of LB-100 to not only kill cancer cells but also potentially change their behavior is an encouraging prospect. Moreover, the fact that resistance to LB-100 correlates with decreased malignancy could imply a reduction in the severity of the disease even when the drug doesn't eliminate the cancer entirely. This is a fresh take on the often-discouraging narrative of drug resistance in oncology.

It's important to dissect the implications of LB-100's pre-clinical data from a research and development standpoint. The study's lead by Professor René Bernards, a prominent figure in molecular carcinogenesis, adds a layer of credibility to the findings. However, it's important to remain cautious, as the leap from pre-clinical to clinical efficacy is a significant one. Many compounds that show promise in animal models and cell cultures do not always translate into effective human treatments due to complex biological variables.

Nonetheless, the potential for LB-100 to enhance the efficacy of existing treatments, such as checkpoint immunotherapy and chemotherapy, is noteworthy. If LB-100 can indeed be synergistic with these treatments, it may open up new avenues for combination therapies that could improve patient outcomes. This could be particularly valuable in hard-to-treat cancers where current treatment options are limited. The research community will be watching closely for the results of the clinical trials to validate these pre-clinical findings.

For investors, the news of LB-100's synergistic effects with WEE1 inhibition is a development with potential financial implications. LIXTE Biotechnology Holdings, Inc.'s stock could see fluctuations based on the market's perception of the drug's future prospects. The transition from pre-clinical to clinical studies is a pivotal moment for any pharmaceutical company, often serving as a catalyst for stock movement. Investors typically look for a strong scientific rationale, which appears to be present here and a clear path to market.

However, the financial impact will heavily depend on the outcomes of the clinical trials. Positive results could lead to increased investor confidence and potentially partnerships or licensing deals, whereas negative results could have the opposite effect. Additionally, the novelty of the treatment strategy could attract interest from larger pharmaceutical companies seeking innovative cancer therapies to bolster their pipelines. It's a high-risk, high-reward scenario that requires careful monitoring of the forthcoming clinical data.

LB-100 IS SYNERGISTIC WITH WEE1 INHIBITION IN KILLING CANCER CELLS; FINDING OPENS NEW TREATMENT STRATEGY IN ADDITION TO THREE CURRENT LIXTE CLINICAL TRIALS

PASADENA, CA, March 27, 2024 (GLOBE NEWSWIRE) -- LIXTE Biotechnology Holdings, Inc. (“LIXTE” or the “Company”) (Nasdaq: LIXT and LIXTW), a clinical stage pharmaceutical company, announced today publication of pre-clinical data in the online journal, Cancer Discovery, showing that its lead clinical compound, LB-100, can force cancer cells to give up their cancer-causing properties in a paper entitled “Paradoxical activation of oncogenic signaling as a cancer treatment strategy.” The finding opens a potentially new treatment strategy in addition to LIXTE’s current three clinical trials.

As will be published in the July 2024 issue and posted online today, LB-100 was shown to trigger hyper-activation of the signals that are responsible for the deregulated proliferation of cancer cells, which is the opposite of most of the current generation of cancer therapies. The deliberate hyper-activation of cancer signals becomes lethal when combined with an inhibitor of the WEE1 kinase. This well-tolerated combination proved to be highly effective in killing colon cancer cells in animal models of cancer and in cell culture.

Resistance to therapy is the leading cause of death due to cancer. Resistance to LB-100 therapy, however, has been shown to be associated with cancer cells becoming less malignant. Specifically, colon cancer cells that developed resistance to LB-100 had lost many of the features that make the cells cancerous in the first place and were unable to form tumors in experimental animal models.

This “tumor suppressive drug resistance” stems from the unique features of LB-100. Although cancer-causing signals force cancer cells to become more cancerous, the hyper-activation of these signals by LB-100 forces cancer cells to suppress these signals and thus become less cancerous.

The team of scientists reporting these findings was headed by Professor René Bernards at the Netherlands Cancer Institute and Oncode Institute, Amsterdam. Professor Bernards is a a leader in the field of molecular carcinogenesis and is a member of the Board of Directors of LIXTE.

Bas van der Baan, Chief Executive Officer of LIXTE, said, “The effect of LB-100 on cancer cells is unique in that the only way for cancer cells to escape death is to evolve toward a less cancerous behavior. We look forward to testing this concept clinically, which is distinct from the well-characterized enhancement of checkpoint immunotherapy and chemotherapy by LB-100 currently being tested in three clinical trials.

About LIXTE Biotechnology Holdings, Inc.

LIXTE Biotechnology Holdings, Inc. is a clinical-stage pharmaceutical company focused on new targets for cancer drug development and developing and commercializing cancer therapies. LIXTE has demonstrated that its first-in-class lead clinical PP2A inhibitor, LB-100, is well-tolerated in cancer patients at doses associated with anti-cancer activity. Based on extensive published preclinical data (see www.lixte.com), LB-100 has the potential to significantly improve outcomes for patients undergoing various chemotherapies or immunotherapies. LIXTE's new approach has no known competitors and is covered by a comprehensive patent portfolio. Proof-of-concept clinical trials are in progress.

Forward-Looking Statement Disclaimer

This announcement contains certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, and Section 21E of the Securities Exchange Act of 1934. For example, statements regarding the Company's financial position, business strategy and other plans and objectives for future operations, and assumptions and predictions about future activities, including the continuing development of proprietary compounds, the planning, funding, coordination and potential results of clinical trials, the patent and legal costs to protect and maintain the Company's intellectual property worldwide, and the Company’s ability to obtain and maintain compliance with Nasdaq’s continued listing requirements, are all forward-looking statements. These statements are generally accompanied by words such as "intend," anticipate," "believe," "estimate," "potential(ly)," "continue," "forecast," "predict," "plan," "may," "will," "could," "would," "should," "expect" or the negative of such terms or other comparable terminology.

The Company believes that the assumptions and expectations reflected in such forward-looking statements are reasonable, based on information available to it on the date hereof, but the Company cannot provide assurances that these assumptions and expectations will prove to have been correct or that the Company will take any action that the Company may presently be planning. However, these forward-looking statements are inherently subject to known and unknown risks and uncertainties. Actual results or experience may differ materially from those expected or anticipated in the forward-looking statements. Factors that could cause or contribute to such differences include, but are not limited to, regulatory policies, available cash resources, research results, competition from other similar businesses, and market and general economic factors.

Readers are urged to read the risk factors set forth in the Company’s filings with the United States Securities and Exchange Commission at https://www.sec.gov. The Company disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

For more information about LIXTE, Contact: info@lixte.com
General Phone: (631) 830-7092; Investor Phone: (888) 289-5533

or

PondelWilkinson Inc. Investor Relations pwinvestor@pondel.com
Roger Pondel: (310) 279-5965; Laurie Berman: (310) 279-5962


The lead clinical compound of LIXTE Biotechnology Holdings, Inc. is LB-100.

The pre-clinical data on LB-100 was published in the online journal Cancer Discovery.

The team of scientists reporting the findings was headed by Professor René Bernards at the Netherlands Cancer Institute and Oncode Institute, Amsterdam.

The unique feature of LB-100 is its ability to force cancer cells to become less cancerous by hyper-activating cancer signals.

LB-100, when combined with a WEE1 kinase inhibitor, is highly effective in killing colon cancer cells by making them less malignant and unable to form tumors.
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About LIXT

lixte biotechnology holdings, inc. (lixte) is a clinical-stage public (lixt) pharmaceutical company dedicated to discovering drugs for more effective treatments for cancer. lixte has identified molecular signaling pathways altered in disease states and designed compounds that can safely target them in animal models. the current drug portfolio includes inhibitors of protein phosphatases that are critical to cell division and dna damage repair and inhibitors of protein deacetylases that regulate pathways of gene expression and protein degradation. the phosphatase inhibitors enhance the effectiveness of cytotoxic anti-cancer drugs in general as well as radiation therapy making them potentially useful for the treatment of many, if not all, cancers in combination with existing standard chemotherapy regimens and the evolving targeted cytotoxic therapies of personalized cancer medicine. the lead compound lb-100 is in phase i trial and has the potential to be first-in-class. the deacetylase in