Luigi Pavia’s Post

🎯 Precision Targeting in Cancer Therapy: Allosteric CDK4 Inhibition Overcoming the lack of specificity in CDK inhibitors is crucial for effective cancer treatment. Our recent studies introduce a novel approach focusing on allosteric inhibition at the CDK4-cyclin D interface. 🔬 Breakthrough Strategies: Cryptic Allosteric Site: We discovered a cryptic allosteric drug binding site in the protein-protein interface of CDK4-cyclin D, offering a new path to prevent CDK4 activation without affecting CDK6. Mechanistic Insights: Detailed analysis of this interface reveals allosteric sites that offer new pathways for selective inhibition. 🧬 Advancing Drug Discovery: Enhanced Specificity: This approach promises to deliver next-gen CDK4 inhibitors with high specificity, reducing side effects and enhancing therapeutic efficacy. Innovative Therapeutics: Leveraging protein dynamics for drug targeting opens new doors for developing more effective cancer therapies. Explore our full studies to learn how these innovative strategies can transform CDK4 inhibition and advance cancer treatment: https://lnkd.in/exhzPuFX https://lnkd.in/eEW4JgEj #DrugDiscovery #CancerTherapy #CDK4Inhibitors #Biotech #Pharma #ResearchInnovation #AllostericInhibition #MolecularDynamics

LucidQuest Strategic Insights (lqventures.com) >>> Gene&Cell Therapy >> Bladder cancer drugmaker CG Oncology files for IPO as biotech market shows signs of a rebound: CG Oncology, a late-stage California biotech developing a bladder cancer therapy, revealed its plans to go public on the Nasdaq in an SEC filing Tuesday night. The move marks the first IPO filing of 2024 for the biotech industry, which had a dismal 2023 until the last month, when signs of life began to emerge following a series of acquisitions and signals from the Fed that there would be interest rate cuts in 2024, meaning more capital will likely flow into drug development. While CG’s filing is the first of the new year, $CGON might not be the inaugural listing of 2024. Obesity gene therapy developer Fractyl Health had revealed its IPO plans in mid-December, meaning it could land on Wall Street ahead of CG and any other biotechs that might pencil in their plans before or during the rush of the JP Morgan Healthcare Conference next week. By the end of its first year on the public markets, CG could have topline data from a Phase III trial of its bladder cancer treatment candidate cretostimogene, per its S-1 filing. The biotech’s lead study, BOND-003, is testing the drug as a monotherapy in patients with BCG-unresponsive high-risk non-muscle invasive bladder cancer, or NMIBC. Formerly known as CG0070, the oncolytic virus is also being tested in combination with Merck’s Keytruda and in other NMIBC settings alone and in combination regimens. If the first Phase III trial is a success, CG plans to file for approval with a biologics license application. That could happen as soon as late 2024 or early 2025, CEO Arthur Kuan told Endpoints News at the time of the biotech’s $105 million crossover round in August 2023. Less than three months later, the biotech had confidentially filed its IPO plans with the SEC, according to documents revealed Tuesday. What started as Cold Genesys in 2010 is now one of multiple companies creating therapies for bladder cancer, including UroGen, which also plans a 2024 approval request; ImmunityBio, which just secured more money this week as it awaits an April PDUFA following a May 2023 rejection; and gene therapy biotech enGene, which began trading on the Nasdaq after a SPAC combination last November. CG is first attempting to treat patients who are unresponsive to Merck’s Bacillus Calmette-Guérin therapy, which has been in short supply for the past few years. “More than 20,000 patients may not have access to BCG, and that accumulates because that shortage is not going away,” Kuan said in the August interview. The company has ramped up spending over the past two years as it goes through late-stage development, but it still has a hefty balance sheet with $203.7 million in cash, equivalents and marketable securities at the end of September. In… #lucidquest #genetherapy #celltherapy

GRANT NEWS We are delighted announce that we have been awarded a non-dilutive grant from TARGET ALS FOUNDATION, INC in collaboration with Biospective Inc., to support our discovery proof-of-concept studies in our mitochondrial permeability transition pore (#mPTP) inhibitor drug discovery programme for a treatment for Amyotrophic Lateral Sclerosis (#ALS) (also known as Lou Gehrig’s disease or Motor Nuerone Disease, #MND).   The In Vivo Target Validation Program aims to generate high-quality data on candidate therapeutics in Biospective’s modified ALS TDP-43 mouse model, provide access to in-kind funding for a resource-intensive step of drug discovery, and accelerate the progress of candidate therapeutics from preclinical testing towards clinical trials.   NRG Therapeutics’ co-founder and CEO Dr Neil Miller said, “Preliminary experiments using a mouse model of ALS which contains the human gene for TDP-43 showed that our mPTP inihibitor candidate therapeutic reduced brain cell death. However, due to the rapid disease progression in that mouse model, a full assessment of the therapeutic potential was not possible. This project aims to evaluate NRG’s small molecule inhibitor, in the modified ALS TDP-43 mouse model that progresses more slowly. This will allow for a comprehensive assessment of the molecule’s ability to protect mitochondria, reduce brain cell death, and decrease immune system activation. Additionally, the study will measure improvements in muscle function and strength. If successful, this project will provide crucial support for advancing our mPTP inhibitor into clinical trials for ALS.”   We are one of five recipients of the 2024 In Vivo Target Validation grants. Details of the Target ALS 2024 In Vivo Target Validation grant awardess can be found HERE https://lnkd.in/ebpKCN4H See our full press release HERE https://lnkd.in/emNuMGtF   #BioTech #DrugDiscovery #Grant #NeurologicalDisorders #CNS Vad Lazari

The Rare NRG1 Fusion therapeutics market is undergoing a dynamic evolution, driven by advancements in targeted therapies and personalized medicine. As research continues to unravel the intricate mechanisms of NRG1 fusions, novel treatment modalities are emerging, signaling a transformative shift in the landscape of rare cancer therapeutics. The growing understanding of NRG1-driven cancers is propelling the development of innovative drugs, fostering optimism for improved patient outcomes in this evolving market. Currently, some of the major pharma and biotech companies such as Elevation Oncology, Merus N.V., Hummingbird Bioscience, Boehringer Ingelheim, AVEO Oncology, CANbridge Pharmaceuticals Inc. Salubris Biotherapeutics, and others are developing novel Rare NRG1 Fusion drugs. Get a more detailed analysis, at: https://lnkd.in/gQ_7bUFM #healthcare #biotechnology #lifesciences #pharmaceuticalindustry #pharmaceutical #marketresearch #marketforecast #markettrends #consulting #healthcareconsulting #consultingservices #marketforecast

Eli Lilly and Company will expand its RNA pipeline by hedging $1B in biobucks on HAYA Therapeutics in search for preclinical #drugdiscovery in #obesity and related #metabolic conditions. Until now, Haya has used its drug discovery engine to target long noncoding RNAs (#lncRNAs) that are drivers for fibrotic diseases and other conditions associated with aging, including #cancer. Researchers have implicated a host of lncRNAs in the formation of fatty tissue. Haya’s platform enables the identification of lncRNA targets that are specific to different tissues, diseases and cells. Hitting the targets could reprogram cell states. #cardiometabolic #weightmanagement #RNAtherapy

🌟 Exciting Internship Research Project: Targeted Drug Repurposing for TP53-Mutant Cancer Therapy! 🌟 🔬 Abstract: Delving into potential drug repurposing for TP53-mutant cancers, our recent project explored interactions between PRIMA-1, COTI-2, RG7112, and mutant TP53, revealing promising therapeutic potential. Other drugs like Metformin, Auranofin, and Arsenic Trioxide offer new mechanisms for targeting TP53 mutations, underscoring the value of drug repurposing in developing effective treatments. 🔍 Introduction: Targeting TP53 mutations presents a promising therapeutic approach given its crucial role in cellular stress responses. Our research focuses on drug repurposing, strategically evaluating existing drugs for new therapeutic indications to expedite effective treatments for TP53-mutant cancers. 💡 Key Findings: - PRIMA-1: Demonstrates high binding affinity with mutant TP53. - COTI-2: Restores normal function of mutant TP53. - RG7112 (Nutlin-3): Shows robust binding and interaction with mutant TP53. - Additional Drugs: Metformin, Auranofin, and Arsenic Trioxide offer diverse mechanisms for targeting TP53 mutations. 🔧 Methodology: Leveraging tools like NCBI Gene Library, Swiss-Model, and PubChem for molecular docking studies, we assessed binding affinity, stability, and therapeutic efficacy. 📈 Results: Noteworthy findings include strong binding affinity and stable interactions of PRIMA-1, effective binding of COTI-2 with mutant TP53, and robust interaction of RG7112 with mutant TP53. 🔬 Conclusion: Our study highlights the significance of drug repurposing in treating TP53-mutant cancers and emphasizes the need for experimental validation alongside computational predictions. This research sets the stage for future studies and clinical trials in combating TP53-mutant cancers . I want to extend my gratitude to Ethical Edufabrica Pvt. Ltd. and my mentor Ajay Samuel for their invaluable support and guidance in this project. #CancerResearch #DrugRepurposing #TP53 #MolecularDocking #CancerTherapy #Bioinformatics #LifeSciences #Research #Pharmaceuticals #EthicalEdufabrica #CancerBiology #StudentResearch #LinkedInResearch #InnovativeTherapies 

Gene&Cell Therapy >> Merck inks deal with Unnatural Products; CG Oncology’s upsized IPO; Locus gets $24M from BARDA: Plus, news about Outlook Therapeutics and Adicet Bio: Merck and Unnatural Products collaborate: Per the deal, Merck will make an undisclosed upfront payment to the Santa Cruz, CA-based biotech and up to $220 million in milestones. The companies plan to develop macrocyclic therapies for cancer. — Jaimy Lee CG Oncology upsizes IPO: The Phase III bladder cancer biotech increased its offering size from 11.8 million shares to 17 million shares $CGON, per a SEC filing on Tuesday. At the mid-point of its price range of $17.00, CG would raise about $262.8 million in its Nasdaq debut later this month. It set out a $181 million target last week. — Kyle LaHucik BARDA funds CRISPR-based bacteriophage therapy: Locus Biosciences received a second tranche of funding worth $23.9 million. It now plans to conduct a Phase II study of its CRISPR-enhanced bacteriophage therapy, known as LBP-EC01, in patients with urinary tract infections caused by drug-resistant E. coli. The biotech’s contract with BARDA, an office within the Department of Health and Human Services, began in 2020 and is worth $85 million in total. — Lei Lei Wu Outlook Therapeutics gets up to $172M private placement: The funding is expected to carry ONS-51010, an ophthalmic formulation of bevacizumab-vikg, through FDA approval and launch. The company also said the FDA approved the trial protocol for NORSE EIGHT, a study testing the treatment in 400 patients with neovascular age-related macular degeneration. Outlook expects the trial to address the concerns cited by the FDA in a complete response letter in August. At that time, the regulator found issues with the chemistry, manufacturing and control process and identified a “clinical deficiency.” Outlook’s stock $OTLK was up about 14% on Tuesday morning. — Anna Brown Adicet Bio’s $85.2M offering: The clinical-stage T cell therapy company is selling 27 million shares of common stock at $2.40 per share. Adicet is developing allogeneic gamma delta T cell therapies for autoimmune diseases and cancer. — Anna Brown #lucidquest #genetherapy #celltherapy

AbbVie announced today the acquisition of Celsius Therapeutics, Inc. ("Celsius"), a privately held biotechnology company pioneering new therapies for patients with inflammatory disease. Celsius' lead investigational asset is CEL383, a potential first-in-class anti-TREM1 antibody that has completed a Phase 1 clinical study for the treatment of IBD. TREM1 has been identified as a key disease driver gene in IBD, where it is expressed on inflammatory monocytes and neutrophils. In these cell types and others, TREM1 is upstream of multiple known inflammatory pathways and acts as an amplifier of inflammation. "Given the potential relevance of TREM1 as a key driver of inflammation and pathology in IBD and other conditions, we are eager to advance the development of CEL383 with a goal of helping more patients with IBD achieve remission," said Kori Wallace, MDPhD, vice president, global head of immunology clinical development, AbbVie. "AbbVie shares our excitement about the potential of TREM1 inhibition for patients with inflammatory disease," said Tariq Kassum, M.D., chief executive officer, Celsius. "I'd like to thank the Celsius team for their relentless efforts in the discovery of CEL383. We look forward to the further development of this promising program, which we hope will offer a new approach to the treatment of IBD." Under the terms of the agreement, AbbVie has acquired all outstanding Celsius equity for $250 million in cash, subject to certain customary adjustments. #inflammatorydisease #immunology #IBD #acquisition #AbbVie #CelsiusTherapeutics

AbbVie announced today the acquisition of Celsius Therapeutics, Inc. ("Celsius"), a privately held biotechnology company pioneering new therapies for patients with inflammatory disease. Celsius' lead investigational asset is CEL383, a potential first-in-class anti-TREM1 antibody that has completed a Phase 1 clinical study for the treatment of IBD. TREM1 has been identified as a key disease driver gene in IBD, where it is expressed on inflammatory monocytes and neutrophils. In these cell types and others, TREM1 is upstream of multiple known inflammatory pathways and acts as an amplifier of inflammation. "Given the potential relevance of TREM1 as a key driver of inflammation and pathology in IBD and other conditions, we are eager to advance the development of CEL383 with a goal of helping more patients with IBD achieve remission," said Kori Wallace, MDPhD, vice president, global head of immunology clinical development, AbbVie. "AbbVie shares our excitement about the potential of TREM1 inhibition for patients with inflammatory disease," said Tariq Kassum, M.D., chief executive officer, Celsius. "I'd like to thank the Celsius team for their relentless efforts in the discovery of CEL383. We look forward to the further development of this promising program, which we hope will offer a new approach to the treatment of IBD." Under the terms of the agreement, AbbVie has acquired all outstanding Celsius equity for $250 million in cash, subject to certain customary adjustments. #inflammatorydisease #immunology #IBD #acquisition #AbbVie #CelsiusTherapeutics 👉 https://lnkd.in/dJCqX8PW

Gene&Cell Therapy >> Bladder cancer drugmaker CG Oncology files for IPO as biotech market shows signs of a rebound: CG Oncology, a late-stage California biotech developing a bladder cancer therapy, revealed its plans to go public on the Nasdaq in an SEC filing Tuesday night. The move marks the first IPO filing of 2024 for the biotech industry, which had a dismal 2023 until the last month, when signs of life began to emerge following a series of acquisitions and signals from the Fed that there would be interest rate cuts in 2024, meaning more capital will likely flow into drug development. While CG’s filing is the first of the new year, $CGON might not be the inaugural listing of 2024. Obesity gene therapy developer Fractyl Health had revealed its IPO plans in mid-December, meaning it could land on Wall Street ahead of CG and any other biotechs that might pencil in their plans before or during the rush of the JP Morgan Healthcare Conference next week. By the end of its first year on the public markets, CG could have topline data from a Phase III trial of its bladder cancer treatment candidate cretostimogene, per its S-1 filing. The biotech’s lead study, BOND-003, is testing the drug as a monotherapy in patients with BCG-unresponsive high-risk non-muscle invasive bladder cancer, or NMIBC. Formerly known as CG0070, the oncolytic virus is also being tested in combination with Merck’s Keytruda and in other NMIBC settings alone and in combination regimens. If the first Phase III trial is a success, CG plans to file for approval with a biologics license application. That could happen as soon as late 2024 or early 2025, CEO Arthur Kuan told Endpoints News at the time of the biotech’s $105 million crossover round in August 2023. Less than three months later, the biotech had confidentially filed its IPO plans with the SEC, according to documents revealed Tuesday. What started as Cold Genesys in 2010 is now one of multiple companies creating therapies for bladder cancer, including UroGen, which also plans a 2024 approval request; ImmunityBio, which just secured more money this week as it awaits an April PDUFA following a May 2023 rejection; and gene therapy biotech enGene, which began trading on the Nasdaq after a SPAC combination last November. CG is first attempting to treat patients who are unresponsive to Merck’s Bacillus Calmette-Guérin therapy, which has been in short supply for the past few years. “More than 20,000 patients may not have access to BCG, and that accumulates because that shortage is not going away,” Kuan said in the August interview. The company has ramped up spending over the past two years as it goes through late-stage development, but it still has a hefty balance sheet with $203.7 million in cash, equivalents and marketable securities at the end of September. In the first nine months of 2023, it spent $29.8… #lucidquest #genetherapy #celltherapy