HESI Insights - March 2021

Congratulations to the HESI RISK21 Committee whose approach was highlighted in the recent Health Canada Pest Management Regulatory Agency (PMRA) Guidance Document titled “A Framework for Risk Assessment and Risk Management of Pest Control Products.” In the guidance, the PMRA encourages the use of novel and flexible alternative approaches, such as the HESI RISK21 methodology and tools, to achieve the PMRA’s goal of using science-based risk assessment and risk management approaches to protect human and environmental health.

The inclusion of RISK21 in the PMRA Guidance Document demonstrates the practical value of this risk-based approach for contemporary applications and the impact of HESI science on the global scientific community. Click here to read the full report.

In honor of its 50th anniversary, Critical Reviews in Toxicology published a recent special editorial that lists two RISK21 publications among the journal’s top 25 most read papers:

• “A 21st Century Roadmap for Human Health Risk Assessment” (Pastoor et al. 2014;44 Suppl 3:1–5)
• “Risk Assessment in the 21st Century: Roadmap and Matrix” (Embry et al. 2014;44 Suppl 3:6–16).

Click here to read the editorial.

Proteolysis targeting chimeras (PROTAC)/targeted protein degrader-based therapeutic development programs have grown over the past several years, but there is limited public discussion or scientific consensus on the application of rigorous, consistent, and effective methods for assessment of their clinical safety. As a result, the progress of these programs and their ability to support critical patient populations safely and efficiently is inhibited. HESI will hold a virtual PRO-SAFE workshop in August/September 2021 to bring together academic, clinical, regulatory, and nonclinical drug development scientists from around the globe to discuss evolving approaches to translational safety assessment for PROTAC-based therapies.

The specific design and focus of this meeting will be agreed upon by the project supporters but could include the following:

• Presentations/panel discussions on key challenges identified by each stakeholder group (industry, regulatory, clinical, research, academic, etc.) in assessing the safety of PROTAC therapies (e.g., ADME evaluation, off-target effects assessment, etc.)
• Discussion of theoretical case studies (prepared by a multidisciplinary PRO-SAFE project leadership team) to provide participants with a forum to discuss safety approaches in a nonproprietary context and build consensus/raise questions
• Discussion of approaches for off-target safety evaluation that could be common across different PROTAC/protein degradation platforms and could be “validated” by multisite studies
• Development of a “key considerations” framework to guide (not direct) evaluation of a diverse set of PROTAC therapeutics

Participants in the PRO-SAFE event (and follow-up) will benefit from the opportunity to engage in challenging and focused discussions with a diverse set of stakeholders in this rapidly evolving arena. We are currently looking for experts in academia, industry, and clinical research along with regulators to help us design the workshop. If you are interested, please email Connie Mitchell (cmitchell@hesiglobal.org) or Syril Pettit (spettit@hesiglobal.org). We plan to begin meeting in early April 2021 to design the workshop.

The HESI Cardiac Safety Committee recently held a virtual meeting to review its portfolio and discuss plans for the year. With four main working groups and 12 active subteams, the committee has been working diligently to move projects forward despite COVID-19-related delays and competing priorities. The committee is currently working on projects that range from animal studies to complex in vitro systems, mathematical modeling to improve cardiovascular risk prediction, and database creation as well as two active grants from US government entities. The committee was also included in the recent US Food and Drug Administration (FDA) report on “Advancing New Alternative Methodologies at FDA,” demonstrating the Committee’s commitment to furthering alternative approaches.

Learn more about the Cardiac Safety Committee here or contact Jennifer Pierson (jpierson@hesiglobal.org) and E’Lissa Flores (eflores@hesiglobal.org).

HESI is pleased to announce the launch of the inaugural HESI Innovation Prize – an unrestricted cash prize of $80,000 USD. In 2021, the HESI Innovation Prize will recognize an individual(s) who has helped to reduce disproportionate health burdens in underserved populations and/or to promote greater health equity via their work or efforts in one or more of the following areas that are central to HESI’s core operations: (1) safe and effective medicines, (2) food safety and security, (3) chemical and consumer product safety, and/or (4) environmental quality and sustainability. The Prize will recognize impact achieved via research, training/education, and/or programmatic approaches.

HESI will be accepting applications from 1 April  –  30 June 2021. Awardees will be notified of their selection by August 2021 and must be willing to give a presentation about their work to the HESI membership.

For more information, please click here or email hesiprize@hesiglobal.org.

HESI congratulates Dr. Leah Wehmas for being awarded the Johns Hopkins Bloomberg School of Public Health Center for Alternatives to Animal Testing (CAAT) Next Generation Humane Science Award! In addition to being a long-standing eSTAR Committee member, Dr. Wehmas is co-chair of the eSTAR FFPE Working Group and is participating in the PROPAGATE Network project. Congratulations to Dr. Wehmas on this well-deserved award!

Since 2019, HESI is an official observer in OECD meetings of the Working Party on Safety of Novel Foods and Feeds (WP-SNFF). Observer status allows HESI to participate in WP-SNFF meetings that are relevant to the work of the HESI PATB Committee and COMPARE Allergen Database.

HESI’s PATB Committee Senior Scientific Program Manager, Dr. Lucilia Mouriès, and HESI’s newest staff member, Ms. Liisa Koski (Scientific Project Manager for the COMPARE Allergen Database), attended the 28th plenary meeting of this OECD Working Party, held by web meeting on 3–5 March 2021. This year, HESI was one of seven delegations selected to present highlights of their activities at the meeting. Dr. Mouriès presented an overview of HESI PATB activities with emphasis on the committee’s international workshop “From Protein Toxins to Applied Toxicological Testing” held last fall and the COMPARE Allergen Database to more than 90 participants from 41 country delegations and observer organizations.

The OECD WP-SNFF aims to promote international harmonization in the safety assessment of novel foods and feeds by encouraging information sharing, promoting harmonized practices and common frameworks in safety assessment and regulation, and preventing duplication of efforts among countries.

We are grateful to the OECD WP-SNFF for welcoming HESI as an official observer and allowing us to contribute scientific expertise, information sharing, and knowledge exchange about available resources supporting the safety assessment of novel foods and feeds. To learn more about HESI’s efforts in this space, contact Lucilia Mouriès (lmouries@hesiglobal.org) and Liisa Koski (lkoski@hesiglobal.org).

The HESI Translational Biomarkers of Neurotoxicity (NeuTox) Committee, Developmental and Reproductive Toxicology (DART) Committee, and Botanical Safety Consortium (BSC) will present their work at the 2021 Society of Toxicology (SOT) Virtual Annual Meeting & ToxExpo on 22-24 March 2021. Additionally, Dr. Syril Pettit, HESI Executive Director, will participate in the SOT/EUROTOX Debate “Individualized Toxicity Is the Future of Risk Assessment” as the SOT Debater on 17 March 2021.

Wednesday, 17 March 2021
10 AM – 11:15 AM EST
SOT/EUROTOX Debate – Individual Toxicity Is the Future of Risk Assessment

• SOT Debater: Dr. Syril Pettit (HESI)

Monday, 22 March 2021
11:15 AM – 1 PM EST
Poster – CSF Proteome as Fluidic Biomarkers of Neurotoxicity

• Presenting Author(s): Dr. Syed Imam (US Food and Drug Administration)
• Abstract Number/Poster Number: 2482/P220

Tuesday, 23 March 2021
1 PM – 2:45 PM EST
Poster – Quantifying the DARTable Genome for Prediction of Teratogenic Doses: A Case Study Using Retinoic Acid Pathway-Induced Developmental Toxicity

• Presenting Author(s): Dr. Richard Currie (Syngenta), et al.
• Abstract Number/Poster Number: 2763/P229

Wednesday, 24 March 2021
11:45 AM – 2:30 PM EST
Symposium Session – Botanical Mixtures: Predictive Approaches to Evaluating Pregnancy, and Reproductive and Developmental Health

Learn more and register here.

This year, HESI’s Environmental Epidemiology Committee is launching a webinar series to illustrate the critical role epidemiology can play in the field of quantitative risk assessment. Speakers will provide insight on how to best realize the full potential of human studies in risk assessment and regulatory decision-making and will feature ongoing efforts in this space.

Prof. Harvey Checkoway (University of California, San Diego) will kick off the series with a presentation titled “The Contributions of Environmental Epidemiologic Research to Causal Attribution and Risk Assessment.” Click here to read the abstract for the presentation.

Please join us on 18 March 2021 at 1–2 PM EST for Prof. Checkoway’s presentation, which will be followed by a Q&A session. To register for the first webinar, please click here. To learn more about the Environmental Epidemiology Committee or the webinar series, or to suggest speakers, please contact Sandrine Deglin (sdeglin@hesiglobal.org).

Save the date! The 2021 HESI Annual Meeting will be held virtually on 9-10 June 2021. Don’t miss the chance to hear from health and environmental scientists from around the world.

Stay tuned for program and registration details.

It is hard to believe that we are closing in on a full year of working remotely at HESI (and that the same is true for most of you)! I am so very proud of the way that the HESI staff has pulled together to support each other, colleagues and members, and their own families and friends during this turbulent period. As I reflect on it, however, it should perhaps not be at all surprising that this would be the case. HESI has always attracted staff and collaborators who are “doers” and who seek to support the greater good by extending their time, expertise, and energies to others. What a wonderful environment to be a part of – and one that is more essential now than ever.

Syril D. Pettit, DrPH, MEM
HESI Executive Director