HESI Insights - September 2023

THRIVE is a competitive seed grant program designed to support research that helps to predict, reduce, or prevent adverse events associated with life-saving cancer therapy. We are pleased to announce this year’s grant award winners, selected from a large pool of highly competitive proposals received from research around the globe. Each awardee, listed below, will receive $50,000 in funding to support their research in making cancer patient quality of life an active research priority. Congratulations to all the awardees!

	HESI THRIVE Research Study: Circulating Biomarkers of Anthracycline Cardiac Toxicity in Patients with Lymphoma Dr. Aarti Asnani, MD Section Head, Cardio-Oncology | Director, Cardiology Grand Rounds Associate Program Director for Resident Research, Department of Medicine, Beth Israel Deaconess Medical Center Assistant Professor, Harvard Medical School
	HESI THRIVE Research Study: Investigating epigenetic changes in methotrexate-induced cognitive impairment Dr. Jeremy Willekens, PhD Postdoc Fellow, Rutgers Biomedical and Health Sciences Division of Hematology/Oncology
	HESI THRIVE Research Study: Biomarkers to Inform Kidney Toxicities from Immune Checkpoint Inhibitors Dr. Melanie S. Joy, PharmD, PhD, FCCP, FASN Professor, Director of Innovation and Commercialization, Skaggs School of Pharmacy and Pharmaceutical Sciences SPARK/REACH Program, Director of Entrepreneurship Education University of Colorado, Anschutz Medical Campus

The HESI Cardiac Safety Committee seeks Postdoctoral or Early Career researchers working in cardiovascular safety science or a related field for the 2024 Early Career Seminar Award Series. This award offers an opportunity to share your research, learn from and network with experts in the toxicology and safety pharmacology fields from academia, regulatory agencies and pharmaceutical companies.

Award: Selected candidates will receive a $500.00 USD award and be invited to present their research on a public webinar with HESI Cardiac Safety Committee scientists and other invited guests. Webinar dates will be scheduled with the awardees in Q1 2024.

Qualifications and Requirements: Eligible candidates must have a PhD or equivalent degree in biology or related field (cell biology, biochemistry, pathology, biomechanical engineering, or similar); have current post-doc position/appointment or consider themselves an early career scientist (~1-5 years post-academic training) and may not have previously received an award under this program. Open to both domestic and international applicants.

Application: To apply, please send 1 PDF document with the following: 1) completed application form, 2) CV, and 3) one reference letter: to Jennifer Pierson or Claire O’Brien at cardiacsafety@hesiglobal.org.

Deadline for submission: November 1, 2023.

The Cardiac Safety Committee is celebrating 15 years! Read their summer newsletter here. Topics cover new HESI Staff, the 2023 Early Career Seminar Series Awardees and a list of upcoming meetings the committee will be presenting at.

The Protein Allergens, Toxins and Bioinformatics (PATB) Committee is seeking partners to help launch a new project to advance methods for the assessment of gluten-like peptide sequences that could trigger Celiac disease (CD). The proposed pilot study will test the potential of microbial derived peptides to mimic gluten peptides using organoid models.

The project will have relevance for those involved in the evaluation of genetically modified crops, novel foods, or proteins (e.g., for food ingredients) produced via precision fermentation or microbial production systems as well as those with an interest in NAMs for food safety and clinicians/researchers involved in the study of Celiac Disease pathology and immunology.

By involving in vitro NAMs and patient derived materials to generate CD-organoids, this study is anticipated to generate both biological and methodological advancements. We are seeking additional financial support and expertise to ensure that the design and impact of the study is optimized. Your involvement will be enhanced by significant contributions in-kind by a clinical collaborator from Harvard University with expertise in developing these in vitro organoid systems! Peptides will be generated this fall and bench work to launch in early 2024. For more background information, continue reading here.

As with all HESI projects, the success and impact of this initiative will depend on engaging thought leaders and international stakeholders, from government regulators to clinicians, to crop protection, food biotechnology, and biomedical industry experts, academics, and representatives from other relevant organizations.

Interested in finding out more?

Please contact Dr. Lucilia Mouriès at lmouries@hesiglobal.org

The use of botanicals in dietary supplements and other products is increasing. This article and template provide a way for researchers to gather information for studying the toxicity of these natural products in order to improve the quality of data being generated. It outlines resources to collect literature and relevant information to support the design of botanical toxicity studies. These resources provide critical information related to botanical identification, characterization, pre-clinical and clinical data, including adverse effects and interactions with pharmaceuticals.

Improving the rigor and utility of botanical toxicity studies: Recommended resources. Patel et al., 2023. Regulatory Toxicology and Pharmacology. https://doi.org/10.1016/j.yrtph.2023.105471

Learn more about the HESI Botanical Safety Consortium

In this review, we discuss promising applications, challenges, limitations, and key data initiatives needed to enable regulatory testing and adoption of ecNGS – including for advancing safety assessment, augmenting weight-of-evidence for mutagenicity and carcinogenicity mechanisms, identifying early biomarkers of cancer risk, and managing human health risk from chemical exposures.

Error-corrected next generation sequencing – Promises and challenges for genotoxicity and cancer risk assessment. Marchetti et al., 2023.  Mutation Research/Reviews in Mutation Research. https://doi.org/10.1016/j.mrrev.2023.108466

Learn more about the HESI Genetic Toxicology Committee

A training module on RISK21 was given by Drs. Michelle Embry (virtual) and Doug Wolf (in-person) in Canberra, Australia as part of the Australian Pesticides and Veterinary Medicines Agency (APVMA) training week. The course was also made available to a group in Armidale, Australia as a second site. Approximately 30 participants from various Australian government agencies, including pesticides, veterinary medicines, food, and water engaged in the 1-day course over the two sites that included hands-on interactive case studies and group presentations.

Additionally, the HESI Transforming the Evaluation of Agrochemicals (TEA) Committee work and the joint TEA / HESI PBPK project on Opportunities for Overcoming Dog Use in Agrochemical Evaluation and Registration were highlighted as part of the training week by Dr. Doug Wolf.

A pre-conference workshop on RISK21 was given by Drs. Michelle Embry (virtual) and Doug Wolf (in-person) in Perth, Australia as part of the 2023 ACTRA annual meeting. Nearly 30 participants from government, industry, and academia engaged in the 1-day course that included hands-on interactive case studies. The course was well-received and follow-up collaborations are already being planned.

NAMs activities span across several HESI committees, some of which presented at the 12th World Congress on Alternatives and Animal Use in Life Sciences in Niagara Falls this month.

Transforming the Evaluation of Agrochemicals (TEA) Committee Session S402 (Workshop): Unlocking a New NAM-based Paradigm: Transforming the Evaluation of Agrochemicals. #365 Agrochemical Evaluation for the 21st Century: Achieving the Vision. Raechel Puglisi, HESI.
Next Generation Ecological Risk Assessment Committee Session S457 (Symposium): Advances in NAMs for EcoTox Testing & Risk Assessment, Part2: Computational Tools and Frameworks. #69 Leveraging big data & distribution approaches for environmental risk assessment. Kristin Connors, The Procter & Gamble Company.
Emerging Systems Toxicology for the Assessment of Risk (eSTAR) Committee Session S453 (Symposium): New Approaches to Genotoxicity Testing and Risk Assessment. #56 Transcriptomic biomarker validation efforts: lessons learned from a decade of research on the TGx-DDI biomarker for detecting DNA damaging agents. Carole Yauk, University of Ottawa.
Cardiac Safety Committee Session S454 (Symposium): Predictive Toxicology: Data, Development, Delivery, and Application. #739 Chronic drug-induced cardiotoxicity assessment using in vitro human iPSC-cardiomyocytes and human heart slices: a multi-platform study conducted by the HESI Stem Cell Working Group. Dr. Jessica Palmer, Stemina Biomarker Discovery.

To see examples of our ongoing work and links to more scientific program working in the NAMs space click here.

HESI programs in Genetics & Genomics for human and ecological health protection attended the 54th Environmental Mutagenesis & Genomics Society Annual Meeting in Chicago this month. There were presentations posters from the Botanical Safety Consortium, the Genetic Toxicology Technical Committee and the Cell Therapy – TRAcking, Circulation, & Safety (CT-TRACS) Committee. View the talk and poster titles along with great photos from the event here.

HESI programs presenting posters at SPS2023 are listed below. Stop by and connect!

Botanical Safety Consortium

• From neat compounds to complex mixtures: A potential screening strategy for cardiotoxic potential of botanicals. P132. Presented by Matthias Gossmann, innoVitro GmbH & Jennifer Pierson, HESI

Cardiac Safety Committee

• P25 – Heart Rate Corrected JTp and TpTe as Proarrhythmia Biomarkers in Safety Pharmacology Non-Human Primate Studies: Outcome from a HESI Consortium Prospective Study. Presented by Todd Wisialowski, Pfizer
• P26 – An Evaluation of Drug-Induced Blood Pressure Changes in a Standard Canine CV Safety Pharmacology Study: A HESI-sponsored consortium. Presented by Yevgeniya Koshman, AbbVie
• P107 – In Vitro Assessment of Long-Term Cardiotoxicity Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes. Presented by Ralf Kettenhofen, Fraunhofer IBMT
• P138 – Development of a Pharmaceutical Database to support the Nonclinical Evaluation of Drug-Induced Cardiac Toxicity.  Presented by Jennifer Pierson, HESI
• P140 – The Impact of Collaborative Science on Cardiovascular Safety Evaluation – A 10-Year Update of the HESI Cardiac Safety Committee. Presented by Jennifer Pierson & Claire O’Brien, HESI

View meeting website here.

Join us for an insightful and informative Clinician Roundtable focused on the critical topic of “Immunosuppression: Navigating Safety and Efficacy.” This event aims to provide a comprehensive platform for research professionals to exchange knowledge, experiences, and best practices surrounding the challenges and nuances associated with immunosuppressive therapies.
See full program and register here.

The HESI Botanical Safety Consortium 2023 Annual Meeting will be held virtually on Thursday, September 28, 2023 from 8:00 – 4:00 (US Eastern). The meeting is free and open to all. View the agenda and register now on the BSC webpage here!

The HESI DART committee is organizing a Fall workshop which will focus on applications of DART principles to fit attributes of antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs) and other oligonucleotide therapeutics and highlight gaps and challenges associated with determining the most appropriate strategies to account for potential risk to a varied patient population and spectrum of disease conditions. Considerations unique to oligonucleotide therapeutics for DART evaluations that will be discussed include mechanism of action/target engagement, dosing schedule, toxicokinetics and biodistribution, and species or model selection and validation. Speakers will represent institutions actively working in oligonucleotide therapeutic development and will deliver case study examples to illustrate various DART considerations. However, most of this workshop will be reserved for discussion rather than presentation. Reviewing existing DART strategies and initiating discussion on how to address gaps and challenges will help advance the field toward a fit for purpose and robust characterization of DART risk for this class of compounds.

Register here!

For more information, please visit the event page (here) or contact Connie Chen.

Cardiac Safety Committee

• Heart Rate Corrected JTp and TpTe as Proarrhythmia Biomarkers in Safety Pharmacology Non-Human Primate Studies: Outcome from a HESI Consortium Prospective Study, presented by Brian Roche, CRL.

View meeting webpage here.

We were thrilled to host our “Not Just Another NAMs” event in June of this year as a means of engaging a broad community of stakeholders in this critical arena. As you can see in this edition of Insights – and here – HESI is not just another contributor to the NAMs space. We have been a leader in advancing the design and application of NAMs across chemical, drug, food, and consumer product safety (for human and eco applications) for many years, and our footprint continues to grow. To learn more about our progress, be sure to check out the ‘NAM Feature of the Month‘ in future issues of Insights! If you have ideas for other ways HESI can/should be contributing to NAM applications or other groups we should connect with, please contact us at hesi@hesiglobal.org with your ideas!

With best regards,

Syril Pettit, DrPH, MEM, HESI Executive Director