Bcl-xl

BOSTON, July 4, 2025 /PRNewswire/ -- HotSpot Therapeutics, Inc., a biotechnology company pioneering the discovery and development of oral, small molecule allosteric therapies targeting Smart Allostery platform-identified regulatory sites on proteins referred to as "natural hotspots," today announced the presentation of preclinical data from the Company's CARD11-BCL10-MALT1 (CBM) signalosome program at the European Society for Medical Oncology (ESMO) Gastrointestinal Cancers Congress 2025. The CBM signalosome is a molecular hub that serves as a key regulator of multiple oncogenic pathways, including NFkB, JNK, mTORC1 and MYC. As such, the CBM signalosome serves as a critical regulator of tumor development and survival, particularly in KRAS-driven colorectal cancer (CRC), as well as other KRAS-driven cancers, including pancreatic and lung cancer. Leveraging the Company's proprietary Smart Allostery™ platform, HotSpot has discovered small molecule CBM signalosome inhibitors that bind and inactivate the complex, with preclinical data demonstrating dose-dependent tumor inhibition and regression in multiple KRAS-driven tumor models. "While KRAS activation is a prominent genetic feature of CRC, KRAS inhibitors do not yield deep or durable responses for the vast majority of CRC patients. For the first time, we have shown that KRASG12X CRC depends on the CBM signalosome for survival, supporting the significant potential of a CBM signalosome inhibitor to transform the treatment landscape of KRASG12C CRC, as well as additional KRAS-associated solid tumors," said Geraldine Harriman, Ph.D., Chief Scientific Officer of HotSpot Therapeutics. "Leveraging our Smart Allostery™ platform, we have developed potent inhibitors of the CBM signalosome complex, with robust in vitro and in vivo data demonstrating apoptosis and tumor growth inhibition and regression in KRASG12C CRC, providing support for the profound clinical potential of a CBM signalosome inhibitor." The poster presentations describe the following data: HotSpot's CBM signalosome inhibitors demonstrated selectively induced potent apoptosis in KRASG12 CRC cell lines, outperforming KRAS, BCL2 and Bcl-xL inhibitors. In combination with a KRAS inhibitor, HotSpot's CBM signalosome inhibitor achieved complete suppression of downstream signaling in KRASG12X cell lines. HotSpot's CBM signalosome inhibitor demonstrated dose-dependent tumor inhibition or regression both alone and in combination with a KRAS inhibitor in multiple in vivo models. About HotSpot Therapeutics, Inc. HotSpot Therapeutics, Inc. is a clinical-stage biotechnology company that is pioneering a new class of allosteric drugs that target certain naturally occurring pockets on proteins called "natural hotspots." These pockets are decisive in controlling a protein's cellular function and have significant potential for new drug discovery by enabling the systematic design of potent and selective small molecules with novel pharmacology. The Company's proprietary Smart Allostery™ platform combines computational approaches and AI-driven data mining of large and diverse data sets to uncover hotspots with tailored pharmacology toolkits and bespoke chemistry to drive the rapid discovery of novel hotspot-targeted small molecules. Leveraging this approach, HotSpot is building a broad pipeline of novel allosteric therapies for the treatment of autoimmune diseases and cancer. To learn more, visit . HotSpot Investor & Media Contact: Natalie Wildenradt [email protected] SOURCE HotSpot Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

DOVER, Del., June 20, 2025 /PRNewswire/ -- Lomond Therapeutics Holdings, Inc. ("Lomond Therapeutics"), a clinical-stage biotechnology company dedicated to discovering and developing potentially best-in-class and first-in-class medicines for the treatment of hematological malignancies, today announced that the U.S. Food and Drug Administration (FDA) has cleared it's Investigational New Drug (IND) application for a Phase 1 multicenter study evaluating the feasibility, safety, and efficacy of lonitoclax in patients with relapsed/refractory acute myeloid leukemia (AML). Continue Reading "The acceptance of our third U.S. IND is an important milestone for Lomond Therapeutics", said Iain Dukes, Chief Executive Officer of Lomond Therapeutics. "This IND clearance allows us to begin the next stages of our clinical development for lonitoclax focusing on acute myeloid leukemia (AML). Through this Phase 1 study, we aim to advance our understanding of safety, tolerability, manufacturing feasibility and mechanism of action of lonitoclax." Lomond Therapeutics today announced that the U.S. FDA has cleared it's IND application for a Phase 1 multicenter study Post this About Lomond Therapeutics Lomond Therapeutics is a biopharmaceutical company co-founded by Orbimed, Torrey Pines Investment and Dr. John C. Byrd, focused on the discovery and development of best-in-class and first-in-class small molecule inhibitors that target escape mutations in hematologic and solid cancers. The company is utilizing a proprietary hybrid AI platform of Expert Systems Inc., leveraging its key partners proprietary data, chem/bio tools, knowledge and expertise to choose highly valuable molecular mechanism of pathology, to rationally design, accelerate discovery and optimize development of best-in-class and first-in-class therapies. Lomond Therapeutics' goal is to utilize its capabilities and platform to become a leader in developing novel breakthrough medicines to maximize the clinical benefit when treating hematologic and solid malignancies. For more information visit . About Lonitoclax Lonitoclax has earlier reported novel binding, best-in-class potency and selectivity against BCL2, a key pro-survival protein that is overexpressed in many cancers. To mitigate the hematologic and immune toxicities observed with venetoclax, lonitoclax was designed with a unique binding to improve selectivity for Bcl-2 over Bcl-xL. In addition, a shorter half-life and reduced P4503A4 inhibition properties were built into the molecule to mitigate tumor lysis syndrome and drug accumulation risk, respectively. Lonitoclax has demonstrated monotherapy activity in pre-clinical models, as well as synergistic activity when combined with azacytidine, FLT3 inhibitors, and menin inhibitors in AML xenograft models. Unlike venetoclax, lonitoclax had minimal immunosuppressive activity on B cells, CD8 T cells, and NK cells in preclinical models. Lonitoclax has completed a series of healthy volunteer studies where no significant safety signals were observed at exposures where ex vivo activation of caspase in CLL primary cells was observed, a surrogate marker of BCL-2 inhibition in tumors. This emphasizes important advantages over venetoclax and venetoclax-like molecules in safety, tolerability and feasibility of outpatient treatment, enabling the molecule to safely target AML and CLL patients alone and in combination with other targeted therapies. About the Phase 1 Clinical Trial The Phase 1 study will evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of lonitoclax in combination with azacitidine in R/R AML. The study will include a dose escalation and an expansion phase with up to 60 total participants. Lomond Therapeutics is planning to initiate the study in the third quarter of 2025 across multiple investigative sites. Forward Looking Statements This press release contains forward-looking statements. Statements in this press release that are not purely historical are forward-looking statements. Such forward-looking statements include, among other things, references to our product candidates and the development and therapeutic potential thereof, statements regarding the timing, progress and results of our clinical studies and trials for our current product candidates, including statements regarding the timing of completion or initiation of trials, and the reporting of data from our current trials, our plans relating to the clinical development of our product candidates, the beneficial characteristics of our product candidates, the timing of regulatory filings and approvals for our product candidates, our ability to obtain and maintain regulatory approval for our product candidates, the expected potential benefits of strategic collaborations with related and third parties, our technologies for identifying additional product candidates and our business and development plans. Actual results could differ from those projected in any forward-looking statements due to numerous factors. Such factors include, among others, our ability to raise the additional funding we will need to continue to pursue our business and product development plans, the inherent uncertainties associated with developing product candidates and operating as a development stage company, our ability to identify additional product candidates for development, our ability to develop, complete clinical trials for, obtain approvals for and commercialize any of our product candidates, and competition in the industry in which we operate and market conditions. Investors should consult all of the information set forth herein and should also refer to additional risks set forth under the heading "Risk Factors" in Lomond Therapeutics' filings with the U.S. Securities and Exchange Commission (SEC) available at . These forward-looking statements are made as of the date of this press release, and Lomond Therapeutics assumes no obligation to update the forward-looking statements, or to update the reasons why actual results could differ from those projected in the forward-looking statements, except as required by law. Media Contact: Amy Burd CSO [email protected] SOURCE Lomond Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

UBX1325 demonstrated vision gains that were comparable and statistically non-inferior to aflibercept at week 36 in a difficult-to-treat DME patient population UBX1325 generally outperformed aflibercept in a pre-specified subgroup of patients entering the study with CST Company to explore strategic alternatives to advance UBX1325, Tie2/anti-VEGF bispecific, and Tie2 agonistic antibody assets and reduce operational cash burn May 05, 2025 -- UNITY Biotechnology, Inc. (“UNITY”) [NASDAQ: UBX], a biotechnology company developing therapeutics to slow, halt or reverse diseases of aging, today announced complete 36-week results from the Phase 2b ASPIRE clinical trial of intravitreal UBX1325 in patients with diabetic macular edema (DME) who had poor vision despite prior anti-VEGF treatment. The Company previously disclosed 24-week and interim 36-week results from its ASPIRE trial, demonstrating that UBX1325 was non-inferior to aflibercept at most time points through 36 weeks, except for the average of weeks 20 and 24, the primary endpoint. Non-inferior visual gains in Best-Corrected Visual Acuity (BCVA) compared to leading anti-VEGF product UBX1325 was statistically non-inferior to aflibercept at week 36 UBX1325 generally outperformed aflibercept in subjects who had moderately aggressive disease (central subfield thickness (CST) Favorable safety and tolerability profile UBX1325 continues to demonstrate a favorable safety and tolerability profile across multiple clinical studies to date There have been no cases of intraocular inflammation, retinal artery occlusion, endophthalmitis or vasculitis across multiple studies “UBX1325 has demonstrated the potential to provide a much-needed alternative treatment to anti-VEGF therapy through a completely novel mechanism of action,” said Anirvan Ghosh, Ph.D., chief executive officer of UNITY. “UBX1325’s demonstration of non-inferiority to aflibercept at 36 weeks and superior vision gains in the subgroup of patients with CST under 400 microns underscores its potential to provide a valuable treatment option to patients. We believe that further development of UBX1325 would benefit from the capabilities of a company with an existing ophthalmic franchise, and we are exploring partnerships so that this program can continue to be advanced as a potential new treatment. I am proud of the valuable contributions our team has made in advancing a new therapeutic concept for DME, as featured in our recently published article in NEJM Evidence.” The Company will present full 36-week results from the ASPIRE study at the Association for Research in Vision and Ophthalmology (ARVO) 2025 Annual Meeting on Wednesday, May 7, 2025. Corporate Update: In conjunction with the full 36-week results, the Board of Directors has also approved a revised operating plan focused on evaluating strategic alternatives while reducing operational cash burn. As part of the operating plan, the Company will be implementing a reduction in force affecting all of its workforce, with certain consulting arrangements in place to close down the ASPIRE study. The Company intends to explore a full range of strategic alternatives, which may include, but are not limited to, the sale, license, monetization and/or divestiture of one or more of the Company’s assets and technologies (including UBX1325, the Tie2/aVEGF bispecific, and the Tie2 agonistic antibody), a strategic transaction, collaboration, partnership, merger, sale, or a winddown or dissolution of the Company. The Company’s Chief Executive Officer, Chief Financial Officer, and Chief Legal Officer will transition into consulting roles with the Company to support in evaluation of strategic alternatives and orderly transition of management roles. The Company may engage external advisors to support the evaluation of strategic alternatives. The Company's exploration of strategic alternatives may not result in the consummation of any transaction or the realization of any value for the Company or its shareholders. UBX 1325 (BCL-xL inhibitor) Clinical data from the Phase 2 BEHOLD Study and the Phase 2B ASPIRE study in patients with DME demonstrate improvement in visual acuity with UBX1325 treatment. UBB 2048 (Tie2/aVEGF Bispecific) Preclinical data indicate strong Tie2 pathway activation and inhibition of VEGF pathways, as well as efficacy in models of retinal disease, with clinical candidate molecule. The molecule targets a validated pathway for treating DME and wet age-related macular degeneration (AMD), with best-in-class potential. UBX2050 (Tie2 agonistic antibody) Preclinical data indicates strong Tie2 pathway activation with clinical candidate molecule with therapeutic rationale for diseases of vascular permeability, including chronic kidney disease, diabetic nephropathy, and vascular dementia. Alpha-Klotho (biologic) Global license agreement with Jocasta Neuroscience, Inc. for development and commercialization in neurological indications, with development milestones, approval milestones, and sales-based royalties. Senescence and Aging biology IP portfolio: Broad and foundational patent portfolio in senescence and other age-related biology for multiple indications including ophthalmology, neurological diseases, pulmonary diseases, kidney-related diseases, cardiac and vascular diseases. ASPIRE is a multi-center, randomized, double-masked, active-controlled Phase 2b study designed to evaluate the safety and efficacy of UBX1325 in comparison to aflibercept in previously treated patients with active DME who are not achieving optimal benefit from standard of care. The study enrolled 52 subjects who were randomized 1:1 to receive either 10 μg UBX1325, or 2 mg of aflibercept control injections every eight weeks for six months after randomization. The primary efficacy endpoint is non-inferiority to aflibercept as assessed by mean change from baseline in Best Corrected Visual Acuity (BCVA) to the average of weeks 20 and 24. Additional information about ASPIRE (NCT06011798) can be found here. UBX1325 is an investigational compound being studied in retinal diseases, including DME, and is not approved for any use in any country. UBX1325 is a potent small molecule inhibitor of BCL-xL, a member of the BCL-2 family of apoptosis regulating proteins. UBX1325 is designed to inhibit the function of proteins that senescent cells rely on for survival. The Phase 2 BEHOLD study in patients with DME demonstrated that a single injection of UBX1325 resulted in a statistically significant and clinically meaningful improvement in mean BCVA through 48 weeks compared to sham treatment. In preclinical studies, UNITY has demonstrated that targeting BCL-xL with UBX1325 preferentially eliminated senescent cells from diseased tissue while sparing cells in healthy tissue. UNITY’s goal with UBX1325 is to transformationally improve real-world outcomes for patients with retinal disease. UNITY is developing a new class of therapeutics to slow, halt, or reverse diseases of aging. UNITY’s current focus is on creating medicines to selectively eliminate or modulate senescent cells and thereby provide transformative benefit in age-related ophthalmologic and neurologic diseases. The content above comes from the network. if any infringement, please contact us to modify.