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Cost Effective and Efficient Progression of Lead Drug Candidates to First in Human Studies in Two Largest Economies in the World: USA and China
This webinar is intended to highlight and discuss: The Process of Drug Discovery to Clinic.
Drug discovery and development can be described as the sum of multiple steps taken by biotech and pharmaceutical companies to identify and study new chemical or biological entities and convert these into approved marketed medical products. The entire process takes, on average, more than 10 years and over $1-2B, to bring a product to market.
During this process the attrition rate at all stages of drug discovery and early development are high; hence, sponsors are seeking ways to conduct early-stage drug development studies in the most cost-effective manner. The other consideration is the timeline needed to reach first in human (FIH) studies– the faster we can conduct these studies, the better it is for companies seeking to advance these leads further into development or sell the promising assets to potential buyers who are prepared to conduct additional clinical trials beyond Phase 1 studies.
The elements of drug development leading to IND submission and the conduct of FIH studies include: Drug Metabolism & Pharmacokinetics (DMPK), Safety/Tox, Bioanalytical (GLP/non-GLP) and CMC. With limited and dwindling resources in biotech/pharmaceutical companies, a significant portion of the task of advancing lead compounds to clinical are now conducted by Contract Research organizations (CROs) who are very well equipped to conduct these early development studies. Very often study sponsors struggle to outsource studies, often in small pieces, to reliable CROs.
Managing the costs and tracking timelines/samples/reports at multiple CROs often become a very inefficient and costly task. It is important to seek CROs that can provide a one stop shop option to drive cost-savings and efficiency, including accelerated timelines to reach FIH studies. Furthermore, proper project management, resolving issues with the best available science, and ability to provide proper/relevant regulatory guidance, are essential components of this one stop shop facilities. To keep the prices manageable (especially with the high attrition rate), many sponsors are also seeking more cost-effective alternatives overseas, including conducting studies in countries such as China (second largest economy in the world).
Frontage Labs has been engaged in R & D activities over the last 20+ years, with substantial investments in facilities in both USA and China. Over the years, it has built a full-service science-driven organization that has participated in bringing products to the market for numerous clients. With its dual presence in USA and China, and being a strong science and issue driven organization, Frontage is now offering end to end services to advance clients’ lead candidates to FIH at very reasonable cost (estimated to be 50% less than what it costs to conduct these studies internally or outsource to multiple vendors) and with constricted timelines.
In this presentation we will describe the complete package that Frontage offers to clients seeking to advance their lead candidates to FIH and beyond.
This webinar is sponsored by Frontage.
Highlights of the in vitro Sections of the Draft ICH Drug Interaction Studies M12 Guideline and Comparison With Current Guidance
This symposium is intended to provide perspectives on the impact that the ICH M12 guideline will have on the in vitro DDI studies required for drug development.
In June 2022, the ICH released the first draft of its harmonized Drug Interaction Studies Guideline (M12). The guideline is the result of several meetings of the Expert Working Group since 2018 with the goal of harmonizing member regulatory agencies' guidelines to create a single guideline that will be used across all member countries. After a review period, the guideline will be adopted in early 2024. This presentation will offer perspectives on the differences between current in vitro drug-drug interaction guidance from the relevant US FDA, EMA and PMDA guidance documents, and how to plan drug development strategies to meet the ICH M12 guideline.
This webinar is sponsored by BioIVT.
The Significance of Primary Human Hepatic Cells in Drug Development Research and its Utilization in Predictive Applications Using the Millifluidic Liver Tissue Chips
This webinar will highlight how primary human cells play a key role in the performance of Liver Tissue Chips, which are at the forefront of drug development technology. The Liver Tissue Chip, which utilizes primary cells such as human hepatocytes and non-parenchymal cells, represents a significant advancement in the field, offering a promising tool for predicting pharmacokinetic profiles, toxicodynamic assessment and drug safety evaluation in alignment with human physiology.
Join us Tuesday, December 5, for a ISSX educational webinar presented by Dr. Chris Mathes, Chief Commercial Officer at AnaBios, and Dr. Shiny Rajan, Director of Tissue Development at Javelin. Together, they will explore the transformative potential of utilizing human primary hepatocytes and liver sinus endothelial cells (LSEC) for in revolutionizing drug development processes. They will discuss how liver tissue chips address the limitations of conventional microfluidic-based tissue chips, offering a physiologically relevant platform for better predict pharmacokinetic endpoints and improve the drug optimization process. Users will learn how Liver Tissue Chips enhance safety assessment and the implications for predicting drug-drug interactions (DDI) and drug-induced liver injury (DILI).
We Are Not "DON" YET: Discovery of Tumor Targeted Glutamine Antagonists Through Prodrug Strategy | Dr. Rana Rais
This webinar is intended to discuss a prodrug approach to target tumors. Developing tumor targeting prodrugs is highly challenging. There are not many successful examples in the field. Effective screening strategies are much needed to enable identification of successful prodrug candidates. This is a great example to spark some new ideas in the field. The enzymatic processes for prodrug cleavage are unique and the successful screening strategy is highly educational for scientists in the field.
Many cancers change their energy metabolic requirements and become "glutamine addicted" for their growth and survival. The glutamine antagonist 6-diazo-5-oxo-l-norleucine (DON) has shown robust efficacy in both preclinical animal models and exploratory clinical studies. Although promising, clinical studies with DON were halted due to its marked dose-limiting toxicities, which were mainly gastrointestinal (GI)-related, as the GI system is highly dependent on glutamine utilization. To overcome these toxicity issues, we sought to develop a DON prodrug that could selectively deliver DON to tumor tissues while sparing normal glutamine-dependent tissues like the GI tract. We designed over 100 prodrugs by installing dual promoeities on DON that can be dislodged by the enriched milieu of esterase and protease enzymes in tumor. Using iterative chemistry and pharmacokinetic efforts, we identified various promising DON prodrugs that showed preferential tumor bioactivation and delivery. Of these, our best DON prodrug, DRP-104 is bio-activated in the tumor while bio-inactivated in gastrointestinal (GI) tissues resulting in 11-fold higher glutamine antagonist delivery to the tumor (target site) versus GI (toxicity site) resulting in robust anti-cancer activity with minimal GI-toxicities. DRP-104, is now being evaluated in Ph1/2a clinical trials in cancer patients (ClinicalTrials.gov Identifier: NCT04471415).
Leone et al., Science 366, 1013-1021 (2019)
Rais et al., Sci. Adv. 8, eabq5925 (2022)
Contains 1 Component(s)
On Wednesday, November 29, ISSX held the 2023 Member Meeting.
The 2023 ISSX Member Meeting was online on Wednesday, November 29, 2023. You can now access the meeting recording to hear important updates from ISSX President, Scott Obach, ISSX President-Elect, Aleksandra Galetin, ISSX Treasurer, Sandy Pang, ISSX Membership Affairs Committee Chair, Marcel Hop, ISSX Transporters Focus Group Chair, Xinning Yang, and the Co-Chairs of the ISSX/JSSX 2024 Meeting, Natalie Hosea and Kiyomi Ito.
Contains 3 Component(s) Recorded On: 10/24/2023
The webinar is intended to highlight the efforts in xenobiotic research and translatability to drug development in Africa. Learning Objectives: 1. To explore the gaps in xenobiotics research in Africa and discuss the implications for drug development and healthcare. 2. To highlight the need for comprehensive genomic data collection and representation in Africa, recognizing the continent's genetic diversity and importance in global research and healthcare initiatives.
There is a global concern arising from contamination of the environment by xenobiotic substances. These substances cause severe damage to terrestrial and aquatic ecosystems, leading to threats to other forms of life, including animals, humans, and plants. Physical and chemical degrading methods have been introduced to mitigate the effects of these harmful substances. Though these approaches could be effective, limitations requiring appropriate changes to bioremediation techniques that would engender the necessary bioconversion of xenobiotics need special attention. Bio-friendly methods that use the metabolic potentials of microorganisms to convert toxicants into harmless products remained untapped in Africa. However, the missing link in xenobiotic research in Africa remains with the fact that most genomic datasets in use are, like most other things in Africa, foreign to the continent, from Australia, Europe, and North America. This is despite the enormous African population, evolutionary history, and genetic diversity. Is there "healthcare delivery justice" in developing therapeutic and pharmaceutical products outside Africa for treating infectious and non-infectious diseases, including clinical trials conducted on less diverse (genetic) populations, yet the effects of such investigations are meant for global use? Is there comprehensive genomic data in Africa to promote xenobiotic research? This presentation throws up these and many other issues.
Uncooperative Drugs in in vitro Transporter Research: Practical Approaches to Address Instability and Nonspecific Binding Challenges
This symposium is intended to provide insights on best practices to address the challenges associated with conducting drug transporter studies with compounds that are unstable, sticky or unstable.
In vitro drug transporter data are critical for understanding drug-drug interaction potential, but those data are only useful if conclusions can be drawn. Researchers are plagued with practical challenges associated with compounds that are unstable, sticky or insoluble, resulting in convoluted or inconclusive results. Three interesting transporter case studies are presented, each highlighting a creative solution to explore perplexing initial results and generate useful data, despite problematic physicochemical characteristics of the drugs involved.
This webinar is sponsored by BioIVT.
Importance of Target-mediated Drug Disposition (TMDD) of Small-molecule Compounds and its Impact on Drug Development | Dr. Guohua An
This webinar is intended to increase the awareness of TMDD in small molecules and highlight the importance of recognizing TMDD of small-molecule compounds during clinical development.
Target-mediated drug disposition (TMDD) is a term to describe a nonlinear pharmacokinetics (PK) phenomenon that is caused by high-affinity binding of a compound to its pharmacologic targets. As the interaction between drug and its pharmacologic target belongs to the process of pharmacodynamics (PD), TMDD can be viewed as a consequence of "PD affecting PK". Both large-molecule and small-molecule compounds can undergo TMDD. However, TMDD in large-molecule compounds is well known due to its high prevalence, while TMDD in small molecule compounds is more counter-intuitive and has been an overlooked area. Recognizing TMDD in small-molecule compounds is important, as the information can be leveraged to select the appropriate dose regimen, improve clinical trial design, as well as predict pharmacological target occupancy. This webinar summarizes the general pharmacokinetic features that facilitate the recognition of small-molecule TMDD, provides case examples of different classes of small-molecules exhibiting TMDD, highlights the importance of recognizing TMDD of small-molecule compounds during clinical development, and presenting the pharmacometric models that have been used to facilitate the quantitative understanding of small molecules exhibiting TMDD.
Please note slides are not available for this webinar.
Contains 5 Component(s) Recorded On: 09/10/2023
This short course, featured during the 25th North American ISSX Meeting in September 2023, will focus on challenges and advances of transporter mediated drug disposition and translation from preclinical to human.
This short course, featured during the 25th North American ISSX Meeting in September 2023, focuses on challenges and advances of transporter mediated drug disposition and translation from preclinical to human. Drug transporters play an important role in drug disposition, and are often associated with organ toxicity. The short course discusses the transcriptional and post-transcriptional regulation of transporters and the outcomes of the regulation. The ICH M12 step 1 draft guideline is published and currently under public consultation. The short course also discusses the similarity and difference between ICH M12 and the current regulatory guidance, and its application. The conventional allometric method to predict of human dose and pharmacokinetics remains challenging for transporter substrate. The short course introduces the application of PBPK modeling approaches including model development and validation in preclinical species as an optimal tool to translate in vitro transport kinetics to in vivo situation. Assessing transporter drug-drug interactions can be crucial in drug development, and many endogenous metabolites are identified as useful markers for transporter DDIs. The latest advantages of using transporter DDI biomarkers are discussed.
Considerations of Endogenous Biomarkers to Assess Transporter DDIs in Early Drug Development: An IQ Update and Beyond
Bridget Morse, Eli Lilly and Co., Indianapolis, Indiana, USA
Clinical Studies on Pharmacogenomics and DDIs Involving Drug Transporters
Xinning Yang, US Food and Drug Administration, Silver Spring, Maryland, USA
Drug Induced Organ Toxicity: Transporter Roles and Derisking Approaches
Jason Sprowl, University at Buffalo, Buffalo, New York, USA
Approaches to Predict Human PK Profiles for Compounds Undergoing Transporter Mediated Clearance in Early Drug Development: From Dedrick Plot to PBPK Modeling
Xiaomin Liang, Gilead Sciences, Inc. Foster City, California, USA
Chairs: Yurong Lai, Gilead and Jason Sprowl, University at Buffalo, Buffalo, New York, USA
Contains 4 Component(s) Recorded On: 09/10/2023
This short course, featured at the 25th North American ISSX Meeting in September 2023, is aimed at scientists desiring to gain experience in successful IND submissions that enable first-in-human (FIH) studies with clear line of sight to successful approvals.
This short course, featured at the 25th North American ISSX Meeting in September 2023, is aimed at scientists desiring to gain experience in successful IND submissions that enable first-in-human (FIH) studies with clear line of sight to successful approvals. The course is broken into three parts with three experienced lecturers across industry and FDA. The first section covers translational aspects, modeling approaches, and FIH exposure/dose predictions in the context of the desired therapeutic benefit. The next section focuses on the work needed in the preclinical toxicology package (e.g. expected mechanism-based toxicity, off-target toxicity, species selection, target exposure/dose justifications and metabolites). The last section focuses on understanding the absorption, distribution, metabolism, and excretion (ADME) of the investigational drug with a particular emphasis on drug-drug interactions and inclusion/exclusion criteria in the initial FIH studies and the long range view towards drug approval.
A Successful Preclinical Toxicology Package
Shaji Theodore, US Food and Drug Administration, Silver Spring, Maryland, USA
ADME considerations from FIH to Drug Approval
Rosa Sanchez, Merck, West Point, Pennsylvania, USA
Pharmacology and Translational Aspects
Mirjam Trame, Certara, Boston, Massachusetts, USA
Chairs: Christine Fandozzi, J&J, Springhouse, Pennsylvania, USA and Rosa Sanchez, Merck, West Point, Pennsylvania, USA