Core Insights - LIXTE Biotechnology Holdings, Inc. is focusing on developing novel cancer therapies targeting key cellular pathways, with a particular emphasis on high-need cancer indications that currently have limited treatment options [1][10] - The company's lead compound, LB-100, is being evaluated in clinical studies aimed at enhancing the effectiveness of chemotherapy and immunotherapy in treatment-resistant cancers [1][7] Colorectal Cancer - Colorectal cancer is one of the most prevalent cancers globally, with the drug market projected to exceed $18 billion by 2028; approximately 85% of cases are microsatellite-stable (MSS) and do not respond to existing immunotherapies [2][3] - LB-100 is being studied in combination with Roche's atezolizumab in a clinical trial at the Netherlands Cancer Institute, targeting MSS colorectal cancer patients [3] Ovarian Clear-Cell Carcinoma - Ovarian clear-cell carcinoma (OCCC) accounts for about 5-10% of ovarian cancer cases, with current treatments showing limited efficacy and poor long-term outcomes; the global market for ovarian cancer therapies was valued at over $2 billion in 2023 [3][4] - LB-100 is being evaluated in combination with GlaxoSmithKline's dostarlimab in a study at MD Anderson Cancer Center and Northwestern University, with interim data expected in Q4 2025 [4] Soft-Tissue Sarcoma - Soft-tissue sarcomas are rare cancers with limited treatment advancements; the global market for therapies is projected to reach $1.5 to $2 billion by 2030 [5] - A Phase 1b clinical study is being conducted in collaboration with the Spanish Sarcoma Group to evaluate LB-100 in combination with doxorubicin, aiming to enhance chemotherapy effectiveness [6] Development Strategy - LIXTE's clinical programs are aligned with significant commercial opportunities and unmet therapeutic needs, particularly in tumors with poor responses to current immunotherapies [7][8] - LB-100 is a first-in-class PP2A inhibitor designed to sensitize tumors to other treatments, including immune checkpoint blockade and standard chemotherapy [7][10]

Core Insights - LIXTE Biotechnology's LB-100 is highlighted as a revolutionary cancer therapy that induces "lethal activation" in cancer cells, particularly colon cancer, leading to cell death [1][3] - The editorial in Nature Reviews Cancer emphasizes LB-100's unique mechanism of hyperactivating oncogenic signaling, which contrasts with traditional therapies that inhibit these pathways [4][7] - LIXTE is advancing its clinical trials for LB-100, which has shown a favorable toxicity profile and preliminary antitumor activity in phase I trials [6][10] Mechanism of Action - LB-100, a first-in-class PP2A inhibitor, hyperactivates oncogenic pathways, creating mitogenic stress that is lethal to tumor cells, especially when combined with stress-response inhibitors [5][11] - The approach targets the ideal level of oncogenic signaling, pushing it beyond survivable thresholds, which may represent a vulnerability in tumors [4][12] - Recent data indicate that LB-100's combination with WEE1 inhibitors can trigger tumor regression in colorectal and pancreatic cancer models [11][12] Clinical Development - LIXTE is currently conducting proof-of-concept trials for LB-100 in various cancer types, including Ovarian Clear Cell Carcinoma, Metastatic Colon Cancer, and Advanced Soft Tissue Sarcoma [10] - The company has reported prolonged disease stabilization and partial response in patients during early-stage clinical trials [6][10] - The editorial supports LIXTE's research strategy, validating the unique and radical approach of LB-100 in cancer treatment [12]

Core Insights - LIXTE Biotechnology Holdings, Inc. has completed two financings, raising a total of $6.5 million, which has allowed the company to regain compliance for continued listing on Nasdaq [1][3] - The company has announced management changes, including the appointment of Geordan Pursglove as Chairman and CEO, and the addition of two new independent board members [1][3] - Recent findings published in the journal Nature validate LIXTE's ongoing clinical trials with its lead compound, LB-100, for treating ovarian and colorectal cancer [1][2][3] Financing Activities - LIXTE completed a private placement with accredited investors, raising approximately $5 million, and a registered direct offering, raising approximately $1.5 million [3] - The proceeds from these financings will be used for general corporate purposes and working capital [3] Management Changes - Geordan Pursglove was appointed as Chairman and CEO in June 2025, succeeding Bas van der Baan, who became President and Chief Scientific Officer [3] - Jason Sawyer and Michael Holloway, MD, joined LIXTE's Board as independent directors in July 2025 [3] Scientific Developments - The publication in Nature highlights that patients with tumors having inactivating mutations in PPP2R1A showed significantly better overall survival when treated with immune checkpoint blockade therapy [2][3] - LIXTE has initiated a new pre-clinical study in collaboration with the Netherlands Cancer Institute to test the efficacy of LB-100 on "initiated" cells carrying mutations found in cancer cells [3] Product Pipeline - LIXTE's lead compound, LB-100, is a first-in-class PP2A inhibitor that is well-tolerated in cancer patients and has the potential to enhance chemotherapy and immunotherapy [4][5] - Clinical trials are currently in progress for Ovarian Clear Cell Carcinoma, Metastatic Colon Cancer, and Advanced Soft Tissue Sarcoma [5]

Core Insights - LIXTE Biotechnology Holdings, Inc. is focusing on its lead compound LB-100, a first-in-class small molecule inhibitor of protein phosphatase 2A (PP2A), targeting significant unmet needs in the $200 billion global oncology market [2] - The company is advancing clinical trials for LB-100 in three cancer types: Ovarian Clear Cell Carcinoma, Advanced Soft Tissue Sarcoma, and Metastatic Microsatellite Stable Colon Cancer, with expected trial results in the second half of 2025 [3][4][5] Group 1: Clinical Trials and Market Potential - The Phase 1B/2 trial for Ovarian Clear Cell Carcinoma (OCCC) aims to evaluate LB-100 in combination with the checkpoint inhibitor dostarlimab, addressing a cancer subtype that contributes disproportionately to ovarian cancer mortality [3] - The Phase 1B/2 trial for Advanced Soft Tissue Sarcoma (STS) assesses LB-100 combined with doxorubicin, targeting a group of cancers with poor prognosis [4] - The Phase 1B trial for Metastatic Microsatellite Stable Colon Cancer is investigating LB-100 in combination with atezolizumab, focusing on overcoming immune resistance in this prevalent cancer type [5] Group 2: Upcoming Milestones and Market Impact - Preliminary safety and efficacy data for the OCCC trial is expected in Q4 2025, with the global treatment market projected to exceed $750 million by 2028 due to rising incidence and limited targeted therapies [6] - A safety report for the STS trial is anticipated in Q4 2025, with the global STS drug market estimated to reach $2.1 billion by 2030, driven by combination therapies and unmet medical needs [7] - The colorectal cancer therapeutics market is expected to surpass $18 billion by 2030, with MSS disease representing a significant portion of treatment-resistant cases [8] Group 3: Strategic Positioning and Innovation - LIXTE's strategy of targeting PP2A positions LB-100 as a versatile combination agent with broad applicability across various solid tumors, addressing high unmet needs and limited innovation in oncology [9] - The company has a strong intellectual property position with multiple issued and pending patents covering composition, methods of use, and combinations [14] - Ongoing discussions for co-development opportunities with academic institutions and biopharma partners indicate potential for pipeline expansion into additional tumor types [14]

Core Insights - LIXTE Biotechnology Holdings is focusing on its lead compound LB-100, a first-in-class small molecule inhibitor targeting protein phosphatase 2A (PP2A), which plays a crucial role in cell signaling and DNA damage response [2][13] - The company aims to address high unmet needs in the $200 billion global oncology market, particularly in resistant cancers where traditional treatments have limited efficacy [2] Upcoming Catalysts - The Phase 1B/2 trial for Ovarian Clear Cell Carcinoma (OCCC) is designed to overcome platinum resistance by combining LB-100 with carboplatin and paclitaxel, with preliminary efficacy data expected in Q4 2025 [3][4][7] - The ongoing Phase 1B/2 trial for Advanced Soft Tissue Sarcoma (STS) evaluates LB-100 in combination with doxorubicin, with updates on progression-free survival and objective response rate anticipated in late Q3 2025 [5][8] - A Phase 1B trial for Metastatic Microsatellite Stable (MSS) Colon Cancer is actively recruiting, with initial biomarker and response data expected in Q4 2025 [6][9] Market Potential - The global treatment market for OCCC is projected to exceed $750 million by 2028 due to rising incidence and limited targeted therapies [7] - The global STS drug market is estimated to reach $2.1 billion by 2030, driven by the emergence of combination therapies and unmet medical needs [8] - The global colorectal cancer therapeutics market is expected to surpass $18 billion by 2030, with MSS disease representing a significant portion of treatment-resistant cases [10] Platform Potential - LIXTE's strategy of targeting PP2A positions LB-100 as a versatile combination agent applicable across various solid tumors, addressing oncology subtypes with high unmet needs and limited innovation [11] - The company has a strong intellectual property position with multiple issued and pending patents covering composition, methods of use, and combinations [15] - Ongoing discussions for partnership opportunities with academic institutions and biopharma partners for co-development are in progress [15]

Core Viewpoint - LIXTE Biotechnology Holdings has approved a new treasury policy to diversify its corporate reserves into cryptocurrencies, including Bitcoin, highlighting its commitment to strategic capital allocation and long-term shareholder value creation [1][3]. Treasury Policy Details - Under the new policy, up to 25% of LIXTE's corporate treasury may be allocated to cryptocurrencies, with all digital assets securely held by a regulated custodian and transactions adhering to financial, legal, and audit standards [2]. - The updated treasury policy reflects LIXTE's belief in the long-term potential of cryptocurrency to hedge existing treasury assets and deliver returns for shareholders [3]. Strategic and Financial Rationale - The diversification strategy aims to create a more dynamic balance sheet, allowing LIXTE to be agile in capital deployment while benefiting from long-term appreciation in digital assets [4]. - This move aligns with a growing trend among companies adopting cryptocurrencies as part of their treasury management approach [5]. Industry Trend - LIXTE joins a list of public companies utilizing cryptocurrency as a strategic asset class, which is associated with increased institutional attention and greater visibility in financial and technology sectors [5]. - For smaller-cap growth companies like LIXTE, this strategy signals operational sophistication and a progressive approach to capital efficiency [5]. Additional Strategic Benefits - The treasury diversification is intended to hedge against inflation and fiat currency depreciation, enhance liquidity with globally recognized assets, and position LIXTE at the forefront of fintech-enabled financial strategies [9]. - Digital assets are viewed as a potential asymmetric upside to complement LIXTE's biotech growth trajectory [9].

Core Viewpoint - LIXTE Biotechnology Holdings, Inc. has approved a strategic initiative to allocate up to 25% of its treasury to cryptocurrencies, including Bitcoin, reflecting a belief in the long-term potential of digital assets to enhance shareholder value [1][4]. Group 1: Strategic Capital Allocation - The Board of Directors has authorized the allocation of up to 25% of the company's treasury to cryptocurrencies [1]. - The timing and size of cryptocurrency transactions will depend on market conditions and strategic considerations [2]. - The company will hold all cryptocurrency assets with a fully regulated custodian and ensure compliance with financial, legal, and audit regulations [3]. Group 2: Company Overview - LIXTE is a clinical-stage pharmaceutical company focused on developing cancer therapies, with its lead compound, LB-100, showing promise in enhancing chemotherapy and immunotherapy outcomes [4][5]. - The company is engaged in pioneering research in cancer biology, specifically in the area of activation lethality, and has a comprehensive patent portfolio [5]. - Ongoing proof-of-concept clinical trials are being conducted for various cancer types, including Ovarian Clear Cell Carcinoma and Metastatic Colon Cancer [5].

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2025 ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 Commission file number: 001-39717 LIXTE BIOTECHNOLOGY HOLDINGS, INC. (Exact name of registrant as specified in its charter) (State or other jurisdiction of (I.R.S. Employer incorporation or organization) ...

Core Viewpoint - LIXTE Biotechnology Holdings, Inc. has regained compliance with Nasdaq's Listing Rule 5550(b)(1) after successfully closing a $5.0 million placement and a $1.5 million registered direct offering, ensuring its continued listing on the Nasdaq Capital Market [1][2]. Company Overview - LIXTE is a clinical-stage pharmaceutical company focused on developing and commercializing cancer therapies, particularly targeting new areas in cancer drug development [3][4]. - The company's lead clinical compound, LB-100, is a first-in-class PP2A inhibitor that has shown promise in enhancing chemotherapies and immunotherapies for cancer patients [3][4]. Financial Health - The recent capital raises of $5.0 million and $1.5 million have bolstered the company's financial position, allowing it to meet the minimum equity requirement of $2.5 million for Nasdaq compliance [1][2]. - CEO Geordan Pursglove emphasized the company's commitment to maintaining its Nasdaq listing and improving its financial health while pursuing clinical trials for various cancers [3]. Clinical Development - LIXTE is currently conducting proof-of-concept clinical trials for ovarian clear cell carcinoma, metastatic colon cancer, and advanced soft tissue sarcoma [4]. - The company is pioneering a new treatment paradigm in cancer biology known as activation lethality, supported by a comprehensive patent portfolio [4].

Core Insights - Spartan Capital Securities, LLC announced the closing of a $1.5 million registered direct offering for Lixte Biotechnology Holdings, Inc. [1] - The offering involved the sale of 974,026 shares of Common Stock at a public offering price of $1.54 per share [2] - The gross proceeds of approximately $1.5 million will be used for general corporate purposes and working capital [3] Company Overview - Lixte Biotechnology Holdings, Inc. is a clinical-stage pharmaceutical company focused on cancer drug development [2][8] - The company's lead compound, LB-100, is a first-in-class PP2A inhibitor that enhances the effectiveness of chemotherapy and immunotherapy [8] - Clinical trials are currently underway for Ovarian Clear Cell Carcinoma, Metastatic Colon Cancer, and Advanced Soft Tissue Sarcoma [8] Transaction Details - The offering was made under an effective shelf registration statement previously filed with the U.S. Securities and Exchange Commission [5] - Spartan Capital Securities served as the exclusive placement agent for this transaction [1][4] - The transaction reflects a focus on aligning innovative biotech companies with strategic capital for advancing therapies [4]