HESI Insights - August 2022

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 $45,000 in funding to support their research in making cancer patient quality of life an active research priority.

By providing researchers with both seed funding and access to critical networks, THRIVE will enhance the visibility of the patient need, the value of the research, and the reasons that larger funding entities might elect to incorporate these research streams into future funding priorities. To help support THRIVE or learn more, please visit the website here.

HESI CT-TRACS is proud to be a partner in NC3Rs 2022 CRACK-IT challenge “T-ALERT: Animal-free tumourigenicity assessment of CAR-T and other genetically modified T cells”. CRACK-IT challenges provides UK and EU-based academics and SMEs with the opportunity to apply to develop new 3Rs tools, technologies or approaches and engage with new partners. The T-ALERT Challenge aims to develop an in vitro assay that can reliably evaluate tumourigenicity of human-engineered T cell therapies with the potential to be applied to multiple immune cell types.

As a partner, HESI and the CT-TRACS committee will help to create productive relationship between the challenge awardees and organisations that have expertise, data, or other resources that could support successful Challenge dissemination of the resulting technology. The HESI CT-TRACS Tumorigenicity WG will leverage its successful track record of multi-laboratory evaluation of relevant methods and assays in support of tumorigenicity evaluation of cell therapy products in support of the challenge winners.

Elena McDermott, a MSPH student at the UNC Gillings School of Global Public Health, has been working with HESI this summer. She has been supporting the eSTAR Committee’s Carcinogenomics Project by gathering literature on tumor data in rats. These data will help the group develop and refine transcriptomic biomarkers. About the experience, Elena said “Working with HESI this summer has been an eye-opening opportunity for me. Not only do I get to engage in exciting research, but I get to connect with people with various scientific backgrounds, broaden my communication skills, and expand my knowledge of environmental toxicology as it pertains to the real world.” Elena is exploring career opportunities related to toxicology and public health.

Dary Phen, a rising senior at Dartmouth College, is our summer intern for the Botanical Safety Consortium. Dary has been gathering literature on botanical-drug interactions for patients with diabetes or hypertension. This work could help provide recommendations for patients that take both pharmaceuticals and botanicals for treatment. About her experience, Dary said “What I enjoy the most about being a BSC intern is that not only am I able to hone my research skills, I also have the opportunity to learn from the people I work with. In addition, the work I’ve done with HESI has taught me that there are always new areas to be discovered and things to learn, so it is important to remain a lifelong learner in the field of research.” About her next steps, Dary said “I will continue to explore my interest in medicine through research and ultimately, I hope to pursue a higher education to contribute to the biomedical field.”

We are very pleased to announce 3 promotions within the HESI staff this cycle!

Michelle Embry, PhD– now Deputy Director for HESI
This title change (from her former, Associate Director for Env. Science) reflects Michelle’s expanded role in overall organizational strategy and staff and program development – including her role as lead of the new GRATC initiative.

Dr. Sandrine Deglin, PhD – now SENIOR Scientific Program Manager
This promotion reflects Sandrine’s outstanding work in leading Epi, UVCB, TEA, RISK21, and Bioaccumulation programs.

Jennifer Pierson, MPH– now Associate Director for Program Development & Resourcing (formerly Sr Scientific Program Manager)
In this role, Jen will continue her leadership of the Cardiac, CORA, Neurotox committees & leadership of the EIC & Science Foresight efforts. She will also be developing a new role as primary in house expert for government grant development and management.

We are fortunate to have such an outstanding team of staff – everyone has put in excellent work this year and deserves recognition for their efforts to advance HESI’s mission and reputation.

Please join us in recognizing and thanking all of them!
Click to view all HESI Staff

The International Association for Food Protection (IAFP) Annual Meeting was held in Pittsburgh, PA July 31 – August 3, 2022. Dr. Michelle Embry was invited to serve on an international panel to discuss “Strengthening Food Safety Education and Research Across Programs and Departments in Universities,” which was organized by Dr. Rose Omari (CSIR-STEPRI, Ghana; HESI Board of Trustees Member) and Dr. Clare Narrod (JIFSAN). Panelists from Nigeria, South Africa, Ukraine, Canada, and the United States discussed the multidisciplinary nature of food safety, the skills needed by food safety professionals, and creative mechanisms and strategies to develop effective training programs.

In addition, Drs. Omari and Embry were invited to participate in an innovative session, “Get-Connected Market: Connecting IAFP Professionals on Food Safety in Africa.” The session started with several 2-minute “pitch” sessions on potential projects, followed by a free-form discussion with potential collaborators. Rose and Michelle pitched a concept project to evaluate various aflatoxin mitigation strategies across the value chain, and several valuable partnerships and additional ideas were gained from the discussion.

HESI will be attending and sponsoring the 13th International Conference on Environmental Mutagens in Ottawa, Canada.

27 August 2022, 7:30 – 3:30pm, GTTC Committee Workshop
“Advancing the Next Generation of Genetic Toxicology and Cancer Risk Assessment”, Organized/sponsored by HESI Genetic Toxicology Technical Committee (GTTC), Co-chaired by Francesco Marchetti (Health Canada), Bob Young (MilliporeSigma, retired)
Note: separate registration is required

28 August 2022, 10:30am – 12-30pm, eSTAR Committee Presentation
“USATGx-DDI for High-Throughput, High-Content Identification of DNA Damaging Substances”, Carole Yauk, University of Ottawa
Symposium-1: Advancing Mechanistic Analyses in Genetic Toxicology Using High- Content and High-Throughout Methodologies

30 August 2022, 5:00 – 7:00 pm, eSTAR poster presentation
“MicroRNA Biomarkers of Nephrotoxicity Demonstrate Reduced Variability and Altered Directionality in Exosomal Fraction Compared to Unfractionated Urine”, Brian Chorley, US EPA – Poster Session III

31 August 2022, 11:30am – 12:30pm, Botanical Safety Consortium Presentation
“A Strategy for Developing a Framework of Genotoxicity Assays for Safety Assessment of Botanicals”, Dr. Stefan Pfuhler, Procter and Gamble – Platform 7: Risk Assessment, Confederation III – Level 4.

1 September 2022, 9:10am – 10:00 am, Keynote Speaker Presentation
“The Last Mile Problem in Health Protection Sciences”, Syril Pettit DrPH, HESI Executive Director

The Botanical Safety Consortium is planning a workshop during the 70th International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research (GA) in Thessaloniki, Greece. The workshop entitled “Development of a Toolkit to Evaluate Botanical Safety” will take place on Sunday August 28th and will feature talks on the regulation of botanicals, chemical analyses of botanicals for safety assessment, and new approach methodologies for botanical toxicity screening.

See the BSC webpage for workshop details and to register

The Botanical Safety Consortium will have a poster in collaboration with IndoCardia entitled “A Cost-Effective & Accessible In-Silico Method To Rapidly Predict Cardiotoxicity In Botanical Constituents”.

The Targeted Protein Degrader Committee will have a presentation in a continuing education course entitled “Safety Pharmacology Considerations for Large Molecule and Novel Therapeutic Modalities”. Connie Mitchell will give a virtual talk called “Targeted Protein Degraders: Introduction and Potential Safety Challenges”.

The Cardiac Safety Committee will have 3 poster presentations:

• “Assessment of chronic drug treatment‐induced cardiotoxicity ‐ a project of the HESI Stem Cell Working Group” – also a Rapid Fire presentation on September 12th!
• “Biomarker‐BasedIn VitroEvaluation of Chronic Drug Treatment‐Induced Cardiotoxicity: A HESI Stem Cell Working Group Project” – also a Rapid Fire presentation on September 12th!
• “JTpeak Assessment In Ambulatory Dog And Monkey An Update From The HESI Working Group“

The Symposium on September 12th, Class I Antiarrhythmics and Cardiac Conduction Abnormalities- Beyond hERG and QT Prolongation, will feature concepts from the HESI Cardiac ProA Working Group.

View full meeting details

HESI will be attending the International Congress of Toxicology in Maastricht, Netherlands from 18-21 September 2022. Details below.

19 September 2022, 10am – NeuTox Committee Presentation

Session 03: (Target organ): Minimally-invasive Biomarkers of Central Nervous System Toxicity

• Ruth Roberts (Chair and Director of Drug Discovery, University of Birmingham, UK): Overview of Fluidic Biomarkers of CNS toxicity – The HESI Consortium Approach

21 September 2022, 11:00 – 13:00 – HESI PBPK Committee Session

Session 28: Putting the Puzzle Together: Multiple Lines of Evidence to Inform Design and Interpretation of Long-Term, Repeated-Dose Animal Studies to Inform Human Health Risk Assessment [Michelle Embry and Jos Bessems, chairs]

• Nynke Kramer (Wageningen University, NL): In Vitro and In Silico Tools for Estimating Chemical-Specific Kinetic Processes
• Cecilia Tan (United States Environmental Protection Agency, USA): Applying Physiologically Based Pharmacokinetic (PBPK) Modeling to Design and Optimize Animal Toxicity Studies
• Alicia Paini (European Commission, Joint Research Centre, IT): Using Adverse Outcome Pathways (AOPs) to Support Tiered-Testing Strategies for Toxicity Assessment
• Jeanne Domoradzki / Marco Covaro (Corteva Agriscience, USA): Putting the puzzle together: Integrated Weight of Evidence (WoE) Approach to Optimize Animal Toxicity Studies

Poster – HESI Botanical Safety Consortium

• New Approach Methodologies to Evaluate Botanical Safety – poster by Michelle Embry, HESI Botanical Safety Consortium

BSC Annual Meeting: Due to continued uncertainties with COVID-19, feedback from our stakeholders and the goals of the meeting, we have decided to make this year’s Botanical Safety Consortium’s Annual Meeting FULLY Virtual. The meeting will take place on 27 September. The full agenda will be shared in the coming weeks, but our goals will be to communicate updates from the BSC, present talks on chemical analyses and plans for assays, and listen to talks from leading experts related to botanicals and botanical safety. The meeting is free and open to all. Please register here.

HESI’s Developmental and Reproductive Toxicology (DART) committee will be hosting a hybrid workshop in Washington, DC, titled “Interpretation of developmental and reproductive toxicity in regulatory contexts and frameworks”. Space will be limited for in-person attendance, but a virtual option will be available for those who are unable to travel. Registration will open in September.

Keep your eye on the event page here.

For more information contact Connie Chen (cchen@hesiglobal.org)

The Health and Environmental Sciences Institute (HESI) & Safety Pharmacology Society (SPS) present a new, on-demand training opportunity: A closer look at the new ICH E14/S7b Q&A’s and Training Materials. The target audience includes all sponsors (small and large; other stakeholders in pharma), safety pharmacologists and toxicologists participating in the delivery of the nonclinical data, clinicians, and regulators. See the course content below.

Overview of the ICH E14/7B Q&A Training Materials
Introduction – David Strauss, FDA, United States
Integrated Risk Assessment – Zhihua Li, FDA, United States
In Vitro – Derek Leishman, Lilly
In Vivo – Hugo Vargas, Amgen
Conclusions – David Strauss, FDA, United States

Case Studies and Scenarios for 5.1
Moderator: Christine Garnett, FDA, United States
Speakers – Corina Dota, EFPIA & Wendy Wu, FDA, United States
Topics covered: E14 Pathways and New Options, Clinical Scenarios, Integrated Nonclinical Data
(in vitro & in vivo)

Case Studies and Scenarios for 6.1
Moderator: Christine Garnett, FDA, United States
Speakers – Hugo Vargas, Amgen & Flora Musuamba Tshinanu, FAGG-AFMPS, Europe
Topics covered: E14 Pathways and New Options, Clinical Scenarios, Integrated Nonclinical Data
(in vitro & in vivo)
Summary of integrated risk data

Training Goals
1. Recognize when nonclinical data may be used in the regulatory QT assessment, including understanding the difference between 5.1 and 6.1.
2. Recognize quality hERG and in vivo studies:
a. Are the studies of reasonable quality with the appropriate quality measures?
b. Is the study consistent with the performing lab’s experience with reference agents?
3. Gain familiarity with clinical exposure definitions and how margins are defined to understand the hERG and in vivo margin.
4. Recognize a double-negative nonclinical package.
5. Understand what information is needed to justify the integrated QTc risk assessment.
6. Understand that there can be mitigation around some of the nonclinical study features.
7. Understand timing of various assays and how to progress to clinic.
8. Understand the flexibility of these guidelines and what alternatives may be implemented.

This training is being provided complimentary for SPS and HESI members, and offered to nonmembers for $49.00 USD until 31 December 2022.

Click to link to training course

Contact Jennifer Pierson at jpierson@hesiglobal.org for details.

As incoming Chair of the Board of Trustees, it’s a great honor to be writing my first ‘From the Leadership’ piece for insights and I would like to open by offering my sincere thanks to outgoing President Jon Cook and Chair Martin van den Berg for their outstanding leadership. I have learned so much from working with both of them over the last few years. As they step down, HESI is in a great place scientifically and financially to face the next exciting challenges!

Building on this, the depth and breadth of our scientific outreach stands out in this edition of Insights. Ranging from our wonderful new Thrive award winners through numerous planned conference presentations and workshops, we are taking our science out to the world and inviting new collaborators in. Personally, it’s been such a pleasure to work with the team in growing the new area of Targeted Protein Degraders all the way from an idea in late 2021 to a thriving committee in 2022! A real worked example of what can be achieved when HESI brings its know-how to a scientific challenge.

One personal reflection is the level of balance we have on our board, and in our wider assembly. One of HESI’s core values is to ensure balance of sectors, geographies, demographics and scientific disciplines to reflect our membership and our mission to resolve global health and environmental challenges through engagement. But what is less obvious is the strong balance of styles and approaches to leadership among the team. Some of our Board are strong visionaries with ambition and drive towards change, others are strong on detail and tactics while others are strong team players, seeking compromise and ensuring that all voices are heard. Others are excellent legacy guardians, with detailed knowledge of past plans, initiatives and outcomes. Taken together, this diversity in style makes for an excellent and highly collaborative team, striking a balance between consolidation, ambition and inclusivity.

Finally, I would like to close by offering my congratulations to Sandrine, Jennifer and Michelle on their promotions – well done all 3 of you! I look forward to working with you!

Kind Regards,

Ruth Roberts, PhD, FRSB, FRCPath, HESI Chair of Board