Peter Bou Dib, PhD’s Post

𝗖𝗼𝗳𝗳𝗲𝗲 & 𝗖𝗵𝗲𝗺𝗶𝘀𝘁𝗿𝘆 – 𝗣𝗮𝗽𝗲𝗿 #𝟮 𝗧𝗶𝘁𝗹𝗲: Recent Advances in Targeting the “Undruggable” Proteins: From Drug Discovery to Clinical Trials 𝗝𝗼𝘂𝗿𝗻𝗮𝗹: Nature Signal Transduction and Targeted Therapy (https://lnkd.in/ehzFUFzM) 𝗣𝘂𝗯𝗹𝗶𝗰𝗮𝘁𝗶𝗼𝗻 𝗗𝗮𝘁𝗲: 09/06/2023 This past week has been incredibly promising for pharmaceutical development, especially in creating therapeutics for previously unreachable targets. While reading a recent article in Nature Medicine titled, “PROTAC Protein Degraders to Drug the Undruggable Enter Phase 3 Trials,” I thought I should highlight some of the exciting emerging therapeutic modalities. For most of pharmaceutical history, targeted therapeutics have relied on (𝟭) the discovery of a disease-related target (normally an enzyme or other protein) and (𝟮) subsequent development of a small molecule agonist or antagonist of said target. This inherently constrains pharmaceutical development to targets with an active site capable of being inhibited in such a manner. However, many proteins lack such a site and were overlooked as potential targets. Similarly, many targets have been labeled “undruggable” due to complex structure or function. Today, new therapeutic modalities capable of drugging the “undruggable” are closer than ever and the results are promising… The paper discusses a variety of innovative approaches, but one of the most promising is that of targeted protein degradation. In this field, PROTACs have emerged as a powerful tool. PROTACs (Proteolysis Targeting Chimeras) are poly-functional molecules which “hijack” the cell’s natural degradation machinery (ubiquitin proteasome pathway) to eliminate targets of interest. They normally consist of a target ligand, a flexible linker, and an E3 ligase ligand. The PROTAC molecule binds to the target and the E3 ligase simultaneously, bringing them into proximity with one another. This allows the E3 ligase to “tag” the target protein for subsequent degradation. The unique features of the PROTAC mechanism of action are (𝟭) They are not classical inhibitors; Rather than simply impeding native protein activity, they degrade their targets and as such are effective until the protein is synthesized once again by the cell. (𝟮) They are not stoichiometric; One PROTAC molecule can inactivate multiple target proteins whereas a classical small molecule acts on a 1:1 basis. (𝟯) They are highly customizable and do not rely on classical design methods; A PROTAC’s target ligand does not need to bind to specific active site, so long as it can bind to some region of its target, it will generally be effective. We are truly at a turning point in science where we are developing amazing technologies to deal with things we’ve always understood to be a part of the human condition. 

📢 Otsuka Pharmaceutical Co., Ltd. has acquired Jnana Therapeutics🚀 This acquisition has taken place for an upfront $800 million, with an additional $325 million in milestone payments and includes Jnana’s innovative drug discovery platform and a promising rare disease candidate. 🔬 About Jnana Therapeutics: Boston-based Jnana uses a unique approach to discover new drugs by targeting proteins within living cells. Their advanced platform has the potential to tackle challenging protein targets, including those involved in rare diseases. 🌟 Key Highlights: Rare Disease Focus: Jnana's lead candidate targets PKU, a genetic disorder. Early trials show promising results, with a significant reduction in disease symptoms. Strategic Fit: Otsuka sees Jnana’s platform as a perfect match to enhance their existing capabilities, especially complementing their subsidiary, Astex Pharmaceuticals 🌐 What’s Next? Jnana will continue its research and development as a wholly owned subsidiary of Otsuka, moving forward with its groundbreaking work on small molecule therapies. This acquisition is a big step forward in the fight against rare diseases and highlights the power of innovative biotech platforms. How do you think this acquisition will impact the future of drug discovery in the biotech industry? #Biotech #Pharmaceuticals #DrugDiscovery #RareDisease #OtsukaPharmaceutical #JnanaTherapeutics #MedicalAdvancements #PKU

As per DelveInsight’s analysis, the HDAC inhibitor market is anticipated to grow at a significant CAGR by 2034. Leading HDAC inhibitor companies such as Xynomic Pharma, Medivir AB, Tenaya Therapeutics, and others are developing novel HDAC inhibitors that can be available in the HDAC Inhibitor market in the coming years. Some of the key HDAC inhibitors include Abexinostat, Remetinostat, Ricolinostat, and TN-301, among others. Get Detailed Insights here: https://lnkd.in/gyEAVp26 #Healthcare #HDACInhibitors #MarketGrowth #Pharma #Innovation #DrugDevelopment #MarketAnalysis #FutureTrends #HDACInhibitorMarket #GlobalMarket #Pharmaceuticals #HealthcareInnovation #TechInnovation #MarketTrends #HDACIndustry

6September: Thanks to Chris Spivey for inviting me as a panelist with Benjamin McLeod on Pharmaceutical Technology's "Behind the Headlines," where I discussed HAYA Therapeutics' up-to-$1 billion long non-coding RNA collaboration with Eli Lilly and Company, a partnership I recently wrote about for Genetic Engineering & Biotechnology News--as well as a recent GEN story about self-repairing mitochondria, the growth of weight-loss/metabolic drugs like the GLP-1s, the CDC's plan to supply free at-home COVID-19 tests, and the #BIOSECURE Act pending in Congress. https://lnkd.in/ehhhfgjG

As per DelveInsight’s analysis, the EGFR inhibitor market is expected to grow at a notable CAGR by 2034. Leading companies in the EGFR inhibitor space, such as Merus N.V., Taiho Pharmaceutical Co., Ltd., ArriVent Biopharma, and Blueprint Medicines, are actively developing innovative EGFR inhibitors that may enter the market in the coming years. Key EGFR inhibitors in development include Petosemtamab, MCLA-129, Zipalertinib, Furmonertinib, and BLU-945, among others. Get more details here: https://lnkd.in/ghpusREV #EGFRInhibitors #MarketGrowth #Pharma #Oncology #DrugDevelopment #Innovation #CancerTreatment #Biopharma #EGFRResearch #MarketTrends #PharmaceuticalIndustry #FutureTrends #EGFRInhibitorMarket #Biotech #ClinicalTrials #HealthcareInnovation

Deciphera Pharmaceuticals is to be acquired by ONO Pharmaceutical for $2.4 B. This acquisition will not only expand ONO's target oncology portfolio, but also accelerate ONO's business development in the United States and Europe, and strengthen kinase drug discovery research. Deciphera markets Qinlock (ripertinib), a switch-control kinase inhibitor indicated for treatment of fourth-line advanced gastrointestinal stromal tumor (GIST) in adults who have received prior treatment with three or more kinase inhibitors. Also in Deciphera’s pipeline: 1. DCC-3084, a Phase I pan-rapidly accelerated fibrosarcoma (RAF) inhibitor being developed to treat solid tumors and blood cancers. 2. DCC-3009, a pan-KIT inhibitor being developed to treat GIST, now in the IND-enabling phase. 3. Integrated Stress Response (ISR) program, a research-phase general control nonderepressible 2 (GCN2) kinase activator being developed to treat solid tumors #pharmadeals #raslss #oncology #acquisition #pharmaacquisiton #M&A

Otsuka Pharmaceutical Companies (U.S.) Pays Up to $1.1B to Buy Jnana Therapeutics, Adds Drug Discovery Capabilities With an upfront $800 million payment and $325 million in potential milestones, Otsuka Pharmaceutical is acquiring Jnana Therapeutics’ drug discovery platform and rare disease candidate, the companies announced Thursday. Otsuka Pharmaceutical has struck a deal to buy Jnana Therapeutics for $800 million upfront and a potential $325 million in milestone payments for its drug discovery platform and pipeline led by a clinical-phase rare disease candidate, the companies announced Thursday. Jnana discovers potential drug candidates by exposing protein targets to its library of chemical fragments inside living cells. The Boston-based biotech has designed the library to include a wide range of fragments that may bind and covalently label druggable pockets on the target protein. After finding a fragment that binds a target, Jnana screens a library of drug-like compounds to identify small molecules that engage the same part of the protein. Otsuka’s statement on the reasons for the acquisition discussed Jnana’s platform before mentioning the drug candidates it has generated. The Japanese drugmaker said the platform can address hard-to-drug target classes including solute carriers, transcription factors and signaling scaffold proteins. Otsuka sees the platform as complementary to the capabilities of its existing subsidiary Astex Pharmaceuticals. Jnana, like Astex, will operate as a wholly owned subsidiary of Otsuka and will continue its R&D. The biotech has used its platform to find small molecules that inhibit SLC6A19, a transporter responsible for intestinal absorption and renal reabsorption of phenylalanine (Phe). People with phenylketonuria (PKU) are unable to break down Phe. https://lnkd.in/ecgf2Yhs

🔍 Discover DelveInsight's comprehensive Janus kinase (JAK) Inhibitor Market Insights report! This in-depth analysis covers current treatment practices, emerging therapies, and the competitive landscape in the 7MM markets (US, EU-4, UK, and Japan). The Janus kinase (JAK) Inhibitor market is expected to see significant growth through 2034, fueled by increased R&D activity and clinical trials. 🧪 Key companies developing novel JAK inhibitors include Pfizer, Sierra Oncology, Theravance Biopharma US, Inc., Dizal Pharmaceutical, Aclaris Therapeutics, Inc., Celon Pharma S.A. , Incyte, AbbVie, Galapagos, Gilead Sciences, Jiangsu Hengrui Medicine Co., Novartis Pharmaceuticals, Eli Lilly and Company, Kartos Therapeutics, Inc., Telios Pharma, Inc., Kiniksa Pharmaceuticals, Celgene, GSK, Abivax S.A., Constellation Pharmaceuticals, A MorphoSys Company, MaaT Pharma, Galvani Bioelectronics, CTI BioPharma, CRESCENDO BIOSCIENCE CLINICAL LABORATORY, Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Astellas Pharma, IMAGO BIOSCIENCES LTD, Geron Corporation, R-Pharm, Sciencefiles, Vertex Pharmaceuticals Incorporated, Italfarmaco, Suzhou Zelgen Biopharmaceutical Co., Ltd., Bristol Myers Squibb, Cephalon, Karyopharm Therapeutics Inc., and others. Noteworthy therapies include PF-06651600, Momelotinib, TD-8236, Ruxolitinib, Upadacitinib, and Filgotinib. 📈 With its growing pipeline and promising clinical trials, the Janus kinase (JAK) Inhibitor market presents significant opportunities for pharma companies. 💡 Request a Sample Report now and stay ahead of market trends: https://lnkd.in/gv8DSurg #Pharma #JAKInhibitors #MarketResearch #Healthcare #DelveInsight #Biotech #EmergingTherapies #ClinicalTrials #Biotech #Pharma #ClinicalTrials #DelveInsight #MedicalResearch #HealthcareInnovation #PharmaDevelopment #PharmaNews #marketgrowth #marketforecast #healthcare #healthcareconsulting #marketresearch #healthcare #pharmaceutical #business

2023 Novel Small Molecule FDA Drug Approvals | https://lnkd.in/gVa-AfCw The 55 new drug approvals were the second-highest in a decade! 🎉 Notably, the majority (62%) were still small molecules, with many groundbreaking mechanisms. Key Stats: 36% - First-in-Class approvals by the FDA 51% - Orphan Drug Designation for rare indications 45% - Fast Track Designation 16% - Breakthrough Therapies 16% - Accelerated Approval 84% - Approved on their first review cycle Scientifically fascinating examples include: -The first FDA-approved oral ER degrader -The first FDA-approved reversible BTK inhibitor -The first FDA-approved gamma-secretase inhibitor (not in Alzheimer’s!) -A reversible covalent, brain-penetrant Nrf2 activator -The first drug derived from mRNA display screening for macrocyclic peptides -The first PI3K inhibitor with a first approval outside oncology -A factor B-targeting Breakthrough Therapy for paroxysmal nocturnal hemoglobinuria -The first intranasal CGRP antagonist for fast-acting migraine treatment This high-resolution poster breaks down the structures, mechanisms, originators, and indications of these small-molecule drugs. Check out this Open Access full article for more information about each drug, a high-resolution PDF, and links to deeper dives into many of the key approvals from last year. Open Access link: https://lnkd.in/gVa-AfCw

The discovery of drugs targeting fibroblast growth factor receptors (FGFRs) and overcoming resistance to them is a rapidly evolving area in the pharmaceutical industry. Since April 2020, the FDA approved three FGFR inhibitors Pemigatinib, Infigratinib, and Futibatinib for treating different types of cholangiocarcinoma. Gatekeeper mutations have been identified in the FGFR family, including FGFR1 V561M/F, FGFR2 V564M/F, FGFR3 V555M/L, and FGFR4 V550M/L. These mutations are located in the hinge region of the ATP-binding pocket of kinases and play a role in controlling access of TKIs to the hydrophobic ATP binding pocket. The V564F gatekeeper mutation in FGFR2 is a clinically relevant mutation that confers resistance to certain FGFR inhibitor drugs. Upon the introduction of a larger phenylalanine residue, the protein's back pocket region becomes more enclosed, restricting the accommodation of molecules within this space. Researchers from Kinnate Biopharma have discovered KIN-3248, a clinical candidate that is being evaluated for the treatment of advanced tumors harboring FGFR2 and/or FGFR3 gene alterations. To overcome V564F mutation, they focused on designing compounds with a strong anchoring interaction with the backbone NH of the DFG-Asp residue accompanied by reduction of steric bulk near the gatekeeper residue. The novel article recently published in J. Med. Chem discusses the drug discovery strategies and the comparison of KIN-3248 in vivo tumor suppression potency to other FGFR inhibitor approved drugs. KIN-3248 is a selective, irreversible pan-FGFR inhibitor that can inhibit secondary kinase domain mutations associated with progression to resistance. It is of particular interest for gatekeeper mutations such as V564F and molecular brake mutations, both resistant to Pemigatinib, Infigratinib, and Futibatinib. It is an amazing medicinal chemistry story to read. https://lnkd.in/dNDRByHT