DOCSLIB.ORG

Drug Development Snapshot

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Drug Development Snapshot BIOTECH PRIMER’S COURSE SNAPSHOT Drug Development Drug Development Live, Online Master Courses Choose from our prescheduled, signature courses or let us customize the course based on your needs and bring it onsite to your organization. Drug Discovery for the Scientist one-day course ����������������������������������������������������4 Preclinical Development for the Scientist one-day course ...................................6 Drug Development Immersion two-day course �������������������������������������������������������8 Understanding Commercialization Within Biopharma two-day course �����������11 On-Demand Master Course Recordings Cannot make our live, online class? Take the same class but in its recorded version. Same content, interactive exercises, and course material. Depending on the length of the course you have 1-3 months to view. Drug Development Immersion 9-hour course.......................................................14 On-Demand, Online Classes Learn anywhere, at your own pace. Designed for individuals, customized for organizations. The Regulatory Process 60-minute online class .......................................................18 Drug Discovery of Small Molecules 55-minute online class �����������������������������������20 Drug Discovery of Biologics 45-minute online class ................................................21 Preclinical Development 55-minute online class .....................................................22 Clinical Development 101: General Principles 55-minute online class ����������������23 BiotechPrimer.com BIOTECH PRIMER, INC. COPYRIGHT 2021 | 2 On-Demand, Online Classes (continued) Clinical Development 201: Phase I 50-minute online class ................................... 24 Clinical Development 301: Phase II/III 55-minute online class ������������������������������25 Clinical Development 401: Phase IV 50-minute online class ����������������������������������26 For more information contact Stacey Hawkins T. 410.377.4429 [email protected] Class registration @ BiotechPrimer.com BiotechPrimer.com BIOTECH PRIMER, INC. COPYRIGHT 2021 | 3 Drug Discovery for the Scientist ONE-DAY LIVE, ONLINE COURSE OVERVIEW Drug Discovery for the Scientist is a one-day, intensive course specifically designed for scientists who need to better understand the drug discovery process using an application of risk assessment and multi-disciplinary approaches with considerations for how best to get medicine to patients. Learn from an industry expert what it takes to validate targets, screen molecules to select a lead candidate and to inform an investigational new drug (IND) or clinical trial (CTA) application. Five Takeaways: 1. Fluency in drug discovery process including major milestones. 2. Selection of pharmacologically relevant targets. 3. Criteria to eliminate candidates. 4. Key development considerations for antibodies, cell and gene therapies. 5. Required regulatory studies and data to enable an IND or CTA. BiotechPrimer.com BIOTECH PRIMER, INC. COPYRIGHT 2021 | 4 AGENDA Target Validation 9:00-9:45 Gene Therapy 12:45-1:15 Drug development process overview Screening systems: in silico, in vivo, in vitro Stage gates Identifying potential safety issues Survey of druggable and undruggable targets Target ID, selection, key considerations Safety: Off-Target Screening 1:15-1:45 Target platforms and libraries Screening systems: in silico, in vivo, in vitro Identifying potential safety issues Break 9:45-10:00 Break 1:45-2:00 Lead Optimization 10:00-11:15 How to prioritize leads Analytical and Bioanalytical Assays High-throughput screening techniques 2:00-2:30 How to eliminate candidates Assay development Affinity maturation, antibody diversity Assay validation IgG subtype, alternate formats Supporting cGMPs and GLP Packet Insert Activity 11:15-11:30 Enabling Clinical Trials 2:30-3:15 Quality Cell-Based Therapy 11:30-12:00 Pharmacology Screening systems: in silico, in vivo, in vitro Pharmacokinetics Identifying potential safety issues Toxicology Required studies/data to enable IND/CTA Lunch 12:00-12:45 Wrap-Up 3:15-3:30 BiotechPrimer.com BIOTECH PRIMER, INC. COPYRIGHT 2021 | 5 Preclinical Development for the Scientist ONE-DAY COURSE OVERVIEW Preclinical Development for the Scientist is a one-day, fast-paced course specifically designed for scientists who need to better understand the regulatory requirements of preclinical development. Learn from an industry expert the approaches and criteria used to support a development candidate’s nomination for an IND or CTA to enable first-in-human studies. Five Takeaways: 1. Fluency in preclinical/nonclinical development including required milestones. 2. Typical approaches and criteria used to support development candidate nominations for first- in-human trials. 3. Species selection and use of animal pharmacokinetics in describing the expose-response relationships. 4. Importance of toxicology in selecting compounds and establishing safety. 5. Estimating safe starting dose levels for clinical trials. BiotechPrimer.com BIOTECH PRIMER, INC. COPYRIGHT 2021 | 6 AGENDA CMC 9:00-9:45 Lunch 12:15-1:00 Upstream and downstream bulk processing Cell line and cell bank development Non-Clinical Development Considerations Formulation, fill and finish in Pre-IND/IND 1:00-1:45 Stability and analytical testing of protein Quality products Pharmacology, pharmacokinetics and toxicology Pharmacology 9:45-10:45 Required regulatory studies/data to enable Required data including publications IND/CTA Binding, potency, receptor occupancy Efficacy improvement Break 1:45-2:00 Qualitative and quantitative endpoints In vitro and in vivo models Integrated Development 2:00-2:45 Packaging CMC/nonclinical/clinical data for Break 10:45-11:00 IND Pharmacokinetics 11:00-11:30 IND Requirements 2:45-3:15 Absorption, distribution, metabolism, IND components elimination Common technical document format PK/PD, exposure-response relationships Regulatory process Noncompartmental analysis, AUC, Cmax Wrap-Up 3:15-3:30 Toxicology 11:30-12:15 Criteria to support candidate nomination Dose level selection, routes of administration Species selection, therapeutic margins Defining adverse effects Estimating safe starting dose levels BiotechPrimer.com BIOTECH PRIMER, INC. COPYRIGHT 2021 | 7 Drug Development Immersion LIVE, ONLINE | LEVEL ONE OVERVIEW Drug Development Immersion is a two-day, interactive course that explores the regulatory, commercial, and scientific factors that enable a drug to be successfully brought to market. Discussion features both small molecule drugs and biologics. Our instructors illustrate the corporate decision-making process with personal accounts, giving participants unique insight into strategic development. Learn from an industry expert what it takes to get a molecule from the bench into the marketplace. Drug Development Immersion was developed for the non-science professional who works within or services the biopharma industry. Five Takeaways: 1. Fluency in essential terminology and acronyms used in clinical development 2. In-depth look at the FDA and EMA regulatory process and sponsor interactions 3. Criteria for preclinical studies to support first in human clinical trials 4. Rationale, special considerations, and study design for both traditional and non-traditional clinical trial phases 5. Understanding of the launch process, life cycle management, and post-approval drug safety monitoring BiotechPrimer.com BIOTECH PRIMER, INC. COPYRIGHT 2021 | 8 AGENDA DAY ONE Break 2:00-2:15 Introductions 9:00-9:15 Preclinical Development 2:15-3:15 Setting the Stage 9:15-10:30 Preclinical development pre-IND/CTA Small and large molecule drug characteristics Preclinical data objectives Desirable drug characteristics Safety testing terms Agonist and antagonist drugs Nonclinical studies Route of administration based on drug type Toxicology, pharmacology, pharmacokinetics Traditional drug development pathway IND/CTA filings Gene and cell therapy development pathway Authorization to proceed to clinical trials Drug development metrics Chances of success, timelines and costs Wrap-Up 3:15-3:30 Break 10:30-10:45 The Business of Drug Development 10:45-12:00 Integrated drug development process Stage gates- go/no go decisions Target product profile Draft label Breakout room: draft label activity US patents and market exclusivity Lunch 12:00-12:45 The Regulatory Process 12:45–2:00 Regulatory agencies and compliance worldwide PDUFA, GDUFA, BsUFA Generics and biosimilars approval pathways FDA/sponsor meeting timeline FDA expedited programs Voucher system FDA and EMA orphan drug designation EMA user fees and review times EMA expedited reviews and designations FDA and EMA approval process Regulatory Compliance BiotechPrimer.com BIOTECH PRIMER, INC. COPYRIGHT 2021 | 9 DAY TWO Clinical Development Phase II 1:15-2:00 The Players: Who is involved? 9:00-9:45 Purpose of Phase II Subjects, sponsors, investigators Phase IIA and IIB Ethics committees/investigational review Randomized control trials board Statistical considerations Informed consent Null hypothesis, P value, type 1 and 2 errors Contract research organizations Breakout Room: intro to clinical statistics activity Patient advocacy groups Data monitoring committees (DMC) Clinical Development Phase III 2:00-2:45 How DMC impacts clinical trials Purpose of Phase III Phase IIIB General Principles: Ethics and Risk Trial designs: parallel, crossover, adaptive 9:45-10:30 Database cleaning, lock and unblinding Risk assessment and management Regulatory application submittal
Load more

Recommended publications
  • Preclinical Toxicology – Points to Consider in Program Design
    To view this booklet online, please visit PacificBioLabs.com. Preclinical Toxicology – Points To Consider in Program Design PACIFIC BIOLABS – YOUR PARTNER FOR PRECLINICAL SAFETY TESTING As The Service Leader in Bioscience Testing, Pacific BioLabs (PBL) strives to help our clients deliver safe and effective pharmaceuticals to the patients who need them. Well designed and executed preclinical studies are critical to the success of any drug development program. They must reliably assess the safety of a new drug entity, laying the groundwork for clinical trials and ultimately, regulatory approval. Pacific BioLabs interacts closely with our clients, providing quality nonclinical testing results to meet regulatory requirements and guide your drug development decisions. As part of our commitment to clients, we have prepared a pair of publications that will assist you in planning your preclinical testing program. This publication, Preclinical Toxicology – Points to Consider in Program Design, gives an overview of the drug development process, describes the contents of a typical Common Technical Document, shows the relative timing of various studies required for a successful IND and NDA, and presents advice on selecting and working with contract toxicology labs and other CROs. PBL’s companion publication, Preclinical Toxicology – Guidance for Industry – ICH Guidances, is available on our website at PacificBioLabs.com. It presents two major ICH guidance documents that directly address safety testing of new pharmaceuticals: Guidance M3 – Nonclincal Safety Studies for the Conduct of Human Clinical Trials for Pharmaceutical and Guidance S6 – Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals. The FDA website http://www.fda.gov/cder/guidance contains these two documents along with a variety of other references on regulatory expectations for the nonclinical development of NCEs.
    [Show full text]
  • Research and Development in the Pharmaceutical Industry
    Research and Development in the Pharmaceutical Industry APRIL | 2021 At a Glance This report examines research and development (R&D) by the pharmaceutical industry. Spending on R&D and Its Results. Spending on R&D and the introduction of new drugs have both increased in the past two decades. • In 2019, the pharmaceutical industry spent $83 billion dollars on R&D. Adjusted for inflation, that amount is about 10 times what the industry spent per year in the 1980s. • Between 2010 and 2019, the number of new drugs approved for sale increased by 60 percent compared with the previous decade, with a peak of 59 new drugs approved in 2018. Factors Influencing R&D Spending. The amount of money that drug companies devote to R&D is determined by the amount of revenue they expect to earn from a new drug, the expected cost of developing that drug, and policies that influence the supply of and demand for drugs. • The expected lifetime global revenues of a new drug depends on the prices that companies expect to charge for the drug in different markets around the world, the volume of sales they anticipate at those prices, and the likelihood the drug-development effort will succeed. • The expected cost to develop a new drug—including capital costs and expenditures on drugs that fail to reach the market—has been estimated to range from less than $1 billion to more than $2 billion. • The federal government influences the amount of private spending on R&D through programs (such as Medicare) that increase the demand for prescription drugs, through policies (such as spending for basic research and regulations on what must be demonstrated in clinical trials) that affect the supply of new drugs, and through policies (such as recommendations for vaccines) that affect both supply and demand.
    [Show full text]
  • Drug Discovery and Preclinical Development
    Drug Discovery and Preclinical Development Neal G . Simon , Ph . D. Professor Department of Biological Sciences Disclaimer “Those wh o h ave k nowl ed ge, d on’t predi ct . Those who predict, don’t have knowledge.” Lao Tzu, 6th Century BC Chinese Poet Discovery and Preclinical Development I. Background II. The R&D Landscape III. ItidTftiInnovation and Transformation IV. The Preclinical Development Process V. Case Study: Stress-related Affective Disorders Serendipity or Good Science: Building Opportunity Hoffman Osterhof I. Background Drug Development Process Biopharmaceutical Drug Development: Attrition Drug FDA Large Scale Discovery Pre-Clinical Clinical Trials Review Manufacturing / Phase IV Phase I Phase III 20-100 1000-5000 Volunteers Volunteers 10,000 bmitted 1 FDA Com- bmitted 250 Compounds 5 Compounds uu pound uu AdApproved s Drug NDA S NDA IND S Phase II 100-500 Volunteers 5 years 1.5 years 6 years 2 years 2 years Quelle: Burrell Report Biotechnology Industry 2006 Capitalized Cost Estimates per New Molecule *All R&D costs (basic research and preclinical development) prior to initiation of clinical testing ** Based on a 5-year shift and prior growth rates for the preclinical and clinical periods. DiMasi and Grabowski (2007) II. The Research & Developppment Landscape R&D Expenditures and Return on Investment: A Declining Function Phrma (2005); Tufts CSDD (2005) R&D Expenditures 1992-2004 and FDA Approvals Hu et al (2007) NIH Budget by Area Pharmaceutical Industry: Diminishing Returns “That is why the business model is under threat: the ability to devise new molecules through R&D and bring them to market is not keeping up with what ’s being lost to generic manufacturers on the other end.
    [Show full text]
  • Anticancer Activity of Bicalutamide-Loaded PLGA Nanoparticles in Prostate Cancers
    EXPERIMENTAL AND THERAPEUTIC MEDICINE 10: 2305-2310, 2015 Anticancer activity of bicalutamide-loaded PLGA nanoparticles in prostate cancers JUN GUO1*, SHU-HONG WU2*, WEI-GUO REN3, XIN-LI WANG4 and AI-QING YANG5 1Department of Urology, The Affiliated Hospital of Taishan Medical University, Taian, Shandong 271000; 2Department of Urology, Feicheng Kuangye Central Hospital, Feicheng, Shandong 271608; 3Department of Urology, Rugao Boai Hospital, Nantong, Jiangsu 226500; 4Department of Pathology, The Affiliated Hospital of Taishan Medical University;5 Department of Pathology, The First People's Hospital of Taian, Taian, Shandong 271000, P.R. China Received October 6, 2014; Accepted August 26, 2015 DOI: 10.3892/etm.2015.2796 Abstract. Prostate cancer is the most commonly diagnosed Introduction non-cutaneous malignancy in men in western and most devel- oping countries. Bicalutamide (BLT) is an antineoplastic Men in Western countries and developing nations are hormonal agent primarily used in the treatment of locally frequently diagnosed with cancers of the prostate gland (1). advanced and metastatic prostate cancers. In the present study, Statistically, prostate cancer has overtaken heart diseases and the aim was to develop a nanotechnology-based delivery lung disorders in old people as a cause of mortality. According system to target prostate cancer cells. This involved the to estimates, >200,000 new cases of prostate cancer were development of a BLT-loaded poly(D,L-lactide-co-glycolide) reported with >30,000 mortalities during the year 2013 (2,3). PLGA (PLGA-BLT) nanoparticulate system in an attempt to A similar or higher number of cases has been projected for the improve the therapeutic efficacy of BLT in prostate cancer and year 2014 (4).
    [Show full text]
  • Raloxifene for the Treatment of Triple Negative Breast Cancer
    Raloxifene for the Treatment of Triple Negative Breast Cancer Julian Dzeyk A Thesis Submitted for the Degree of Master of Science At the University of Otago, Dunedin, New Zealand Submitted on February 29th 2012 Acknowledgments I would like to sincerely thank Associate Professor Rhonda Rosengren for giving me the opportunity to work on this project as well as her help and guidance throughout the entire time. I want to greatly thank Dr Sebastien Taurin for teaching me the majority of techniques used in this study, as well as for always being there to discuss my endless questions and thoughts. I have learned a lot from you. Thank you for your continuous help. I would like to thank Babasaheb Yadav for his help and for always bringing a smile or laugh into the lab. You made the ECCO 2011 conference in Stockholm a trip to remember! Thank you. I would also like to thank Mhairi Nimick for her help around the lab, especially for tumor slicing when I had my back problems. To everyone else in the department and especially my fellow MSc students, thank you for the help and the good times. I would also like to thank my family in Germany who have always supported me in my plans and future goals and have always provided me with constructive feedback and ideas. To my dearest Steffi, thank you for your love, and your honest and continuous support. You have been a relentless source of motivation and inspiration. To Andrea and Bernard, thank you for your continuous support, your patience, your constructive criticism, your help, and most of all your love.
    [Show full text]
  • Receptor Af®Nity and Potency of Non-Steroidal Antiandrogens: Translation of Preclinical ®Ndings Into Clinical Activity
    Prostate Cancer and Prostatic Diseases (1998) 1, 307±314 ß 1998 Stockton Press All rights reserved 1365±7852/98 $12.00 http://www.stockton-press.co.uk/pcan Review Receptor af®nity and potency of non-steroidal antiandrogens: translation of preclinical ®ndings into clinical activity GJCM Kolvenbag1, BJA Furr2 & GRP Blackledge3 1Medical Affairs, Zeneca Pharmaceuticals, Wilmington, DE, USA; 2Therapeutic Research Department, and 3Medical Research Department, Zeneca Pharmaceuticals, Alderley Park, Maccles®eld, Cheshire, UK The non-steroidal antiandrogens ¯utamide (Eulexin1), nilutamide (Anandron1) and bicalutamide (Casodex1) are widely used in the treatment of advanced prostate cancer, particularly in combination with castration. The naturally occurring ligand 5a-DHT has higher binding af®nity at the androgen receptor than the non-steroidal antiandrogens. Bicalutamide has an af®nity two to four times higher than 2-hydroxy¯utamide, the active metabolite of ¯utamide, and around two times higher than nilutamide for wild-type rat and human prostate androgen receptors. Animal studies have indicated that bicalutamide also exhi- bits greater potency in reducing seminal vesicle and ventral prostate weights and inhibiting prostate tumour growth than ¯utamide. Although preclinical data can give an indication of the likely clinical activity, clinical studies are required to determine effective, well-tolerated dosing regimens. As components of combined androgen blockade (CAB), controlled studies have shown survival bene®ts of ¯utamide plus a luteinising hormone-releasing hormone analogue (LHRH-A) over LHRH-A alone, and for nilutamide plus orchiectomy over orchiectomy alone. Other studies have failed to show such survival bene®ts, including those comparing ¯utamide plus orchiectomy with orchiectomy alone, and nilutamide plus LHRH-A with LHRH-A alone.
    [Show full text]
  • Establishing a Preclinical Multidisciplinary Board for Brain Tumors Birgit V
    Published OnlineFirst January 4, 2018; DOI: 10.1158/1078-0432.CCR-17-2168 Cancer Therapy: Preclinical Clinical Cancer Research Establishing a Preclinical Multidisciplinary Board for Brain Tumors Birgit V. Nimmervoll1, Nidal Boulos2, Brandon Bianski3, Jason Dapper4, Michael DeCuypere5, Anang Shelat6, Sabrina Terranova1, Hope E. Terhune4, Amar Gajjar7, Yogesh T. Patel8, Burgess B. Freeman9, Arzu Onar-Thomas10, Clinton F. Stewart11, Martine F. Roussel12, R. Kipling Guy6,13, Thomas E. Merchant3, Christopher Calabrese14, Karen D. Wright15, and Richard J. Gilbertson1 Abstract Purpose: Curing all children with brain tumors will require an Results: Mouse models displayed distinct patterns of response understanding of how each subtype responds to conventional to surgery, irradiation, and chemotherapy that varied with tumor treatments and how best to combine existing and novel therapies. subtype. Repurposing screens identified 3-hour infusions of It is extremely challenging to acquire this knowledge in the clinic gemcitabine as a relatively nontoxic and efficacious treatment of alone, especially among patients with rare tumors. Therefore, we SEP and CPC. Combination neurosurgery, fractionated irradia- developed a preclinical brain tumor platform to test combina- tion, and gemcitabine proved significantly more effective than tions of conventional and novel therapies in a manner that closely surgery and irradiation alone, curing one half of all animals with recapitulates clinic trials. aggressive forms of SEP. Experimental Design: A multidisciplinary team was established Conclusions: We report a comprehensive preclinical trial to design and conduct neurosurgical, fractionated radiotherapy platform to assess the therapeutic activity of conventional and chemotherapy studies, alone or in combination, in accurate and novel treatments among rare brain tumor subtypes.
    [Show full text]
  • Redeye Initiates Coverage of Active Biotech with a Cautiously Optimistic View on the New 1.4 3.0 4.4
    Update Equity Research 13 December 2020 Active Biotech Sector: Biotech Derisked and Repurposed FAIR VALUE RANGE BEAR BASE BULL Redeye initiates coverage of Active Biotech with a cautiously optimistic view on the new 1.4 3.0 4.4 strategic direction. Increased clinical activity sets the shares up for several catalysts during next year. The Company is currently raising SEK 76m in a Rights Issue. If the capital raise is fully subscribed, we calculate a base case of SEK 3 per share. ACTI.ST VERSUS OMXS30 OMXS 30 Active Biotech 2,5 Neglected Biotech Re-Emerging from Obscurity 2 Redeye believes the market has so far overlooked Active Biotech’s new focused direction 1,5 and increased project activities. We argue that the repurposing of the core compounds 1 tasquinimod and laquinimod to orphan cancer indication Multiple Myeloma and inflammatory eye disorders, respectively, makes scientific and commercial sense. Also, 0,5 0 we consider the projects as less risky than average from a safety perspective due to 28-okt extensive clinical evidence in other indications. The current valuation is at the bottom end of clinical stage biotech peers, implying low expectations. REDEYE RATING Short Term Factors Shroud Value of Core Projects 4 The shares have dropped about 50 percent in recent months on the back of major 3 shareholder Nordstjernan reducing its holdings > 60 percent, the announcement of a 1 share issue, and a changed protocol for partnered cancer project naptumomab to address antidrug antibody issues. We see upside potential if these concerns are attenuated. We People Business Financials view tasquinimod in Multiple Myeloma as a more valuable project (almost half of the portfolio value).
    [Show full text]
  • Translational Research Process
    Translational Research Process Translational research is often described as having two main areas of translation, referred to as T1 and T2: x T1 involves the translation of basic science discoveries from the laboratory to the clinic (bench to bedside), including completion of preclinical studies and development of human clinical trial protocols. x T2 involves the translation of new therapies/practices resulting from clinical research studies to clinical practice (bedside to community), including adoption of new therapies/practices in clinics in the community. Translational Research Flow The Process from Basic Science Drug Discovery to Clinical Research Early Stage Preclinical Development In this stage, drug discovery is protected for future development, preclinical efficacy is established, and the Investigational New Drug (IND) process is initiated. Late Stage Preclinical Development In this stage, clinical grade drug is produced, toxicity studies required for IND are completed, clinical protocol is developed and IND application is submitted. Go/Hold In this stage, the IND application is reviewed by the FDA, a go or hold Decision decision is rendered. View Drug Discovery: Preclinical Research Development (2-10 years) Detailed Flow for a map describing drug development from concept to implementation. Early Stage Preclinical Development Translational Research Process x Early Stage Preclinical Development x Late Stage Preclinical Development x Go/Hold Decision Protection/Agreements Agreements and protections are needed to ensure successful translation of the research discovery to clinical application in the future. Patent protection is a critical element for successful translation of new drugs to clinical application. You need to ensure you are taking steps to protect your research discovery for future patentability.
    [Show full text]
  • Drug Discovery of Small Molecules 55-MINUTE ONLINE COURSE | LEVEL 1
    Drug Discovery of Small Molecules 55-MINUTE ONLINE COURSE | LEVEL 1 OVERVIEW Drug Discovery of Small Molecules explains the steps involved in discovering new therapeutics. This process includes early screening for targets, target validation, lead optimization, and determining when a target should be transitioned from discovery to development. Learn how new drugs are discovered and optimized prior to being tested in preclinical and clinical trials. Five Takeaways: 1. List and describe the steps of the drug discovery process 2. Define or describe what is a drug and typical discovery platforms 3. Describe target identification and validation processes and screening considerations for drug candidate selection. 4. Explain lead optimization activities, and 5. Discuss typical criteria for advancement of development candidates. AGENDA • Drug Discovery Overview explains the steps involved in drug discovery and how drug discovery fits into the entire process of bringing a new therapeutic to market. • Early Screening defines the term drug and describes some common drug discover platforms, explains target identification processes and screening considerations, and discusses the need for high throughput screening of molecules in drug discovery. • Target Validation defines target validation processes and target selection and discusses some common questions that need to be answered with regard to target-drug interactions. • Lead Optimization Criteria explains lead optimization activities describes examples of drug design methods and approaches, explains ADMET, and gives an example of a screening pathway. • Discovery To Development lists the typical criteria for advancement of potential drug development candidates. Preclinical Development for Small Molecules 55 MINUTES ONLINE COURSE | LEVEL 1 OVERVIEW Preclinical Development For Small Molecules course defines the safety assessment, regulatory requirements and how clinical starting dose levels are estimated.
    [Show full text]
  • ARN-509: a Novel Antiandrogen for Prostate Cancer Treatment
    Published OnlineFirst January 20, 2012; DOI: 10.1158/0008-5472.CAN-11-3948 Cancer Therapeutics, Targets, and Chemical Biology Research ARN-509: A Novel Antiandrogen for Prostate Cancer Treatment Nicola J. Clegg1, John Wongvipat1,2, James D. Joseph10, Chris Tran1, Samedy Ouk9, Anna Dilhas3, Yu Chen1,8, Kate Grillot10, Eric D. Bischoff10, Ling Cai1, Anna Aparicio10, Steven Dorow10, Vivek Arora1,8, Gang Shao10, Jing Qian10, Hong Zhao3, Guangbin Yang3, Chunyan Cao3, John Sensintaffar10, Teresa Wasielewska1, Mark R. Herbert10, Celine Bonnefous10, Beatrice Darimont10, Howard I. Scher8, Peter Smith-Jones4, Mark Klang5, Nicholas D. Smith10, Elisa De Stanchina6, Nian Wu7, Ouathek Ouerfelli3, Peter J. Rix10, Richard A. Heyman10, Michael E. Jung9, Charles L. Sawyers1,2, and Jeffrey H. Hager10 Abstract Continued reliance on the androgen receptor (AR) is now understood as a core mechanism in castration- resistant prostate cancer (CRPC), the most advanced form of this disease. While established and novel AR pathway–targeting agents display clinical efficacy in metastatic CRPC, dose-limiting side effects remain problematic for all current agents. In this study, we report the discovery and development of ARN-509, a competitive AR inhibitor that is fully antagonistic to AR overexpression, a common and important feature of CRPC. ARN-509 was optimized for inhibition of AR transcriptional activity and prostate cancer cell proliferation, pharmacokinetics, and in vivo efficacy. In contrast to bicalutamide, ARN-509 lacked significant agonist activity in preclinical models of CRPC. Moreover, ARN-509 lacked inducing activity for AR nuclear localization or DNA binding. In a clinically valid murine xenograft model of human CRPC, ARN-509 showed greater efficacy than MDV3100.
    [Show full text]
  • Chemoprevention of Breast Cancer and the Trials of the National Surgical Adjuvant Breast and Bowel Project and Others
    Endocrine-Related Cancer (2003) 10 347–357 REVIEW Chemoprevention of breast cancer and the trials of the National Surgical Adjuvant Breast and Bowel Project and others R E Smith and B C Good National Surgical Adjuvant Breast and Bowel Project, Four Allegheny Center, 5th Floor, Pittsburgh, Pennsylvania 15212, USA Requests for offprints should be addressed to R E Smith; Email: [email protected]) Abstract The idea of breast cancer prevention by hormonal means stemmed from the results of treatment trials, many of them carried out by the National Surgical Adjuvant Breast and Bowel Project (NSABP). Over the years, a number of NSABP treatment studies demonstrated that breast cancer recurrence was reduced in women with the disease who were given tamoxifen, a selective estrogen receptor (ER) modulator (SERM). Five subsequent tamoxifen prevention trials with this agent have shown a 48% reduction in ER-positive cancers, but no effect for ER-negative cancers, and an increase in endometrial cancer and thromboembolic events. The drug raloxifene, another SERM, originally examined as an osteoporosis agent, has also shown promise for the prevention of breast cancer, although, as with tamoxifen, the drug carries a risk for thromboembolic events. There is recent evidence in a large treatment trial that the aromastase inhibitor anastrazole, a ‘pure anti-estrogen’, holds promise as a breast cancer preventive agent. Longer follow-up and the testing of additional agents is required before these drugs can be used widely for prevention. In addition, future research should focus on the identification of at-risk women who can perhaps be targeted for specific prevention agents.
    [Show full text]