HESI Global Insights May 2026

HESI Global CGT-TRACS committee is celebrating 10 years of advancing the safety of cell and gene therapies through collaboration!

The HESI Global Cell and Gene Therapy – Tracking, Circulation, & Safety Committee brings together an international, cross sector network of public and private research scientists, regulators, cell and gene therapy developers, clinicians, imaging experts, and enabling tool developers.

Through shared knowledge, experience, and resources, the committee works collaboratively to strengthen safety science for CGTs and support the safe translation of innovative CGTs to the clinic for patients with unmet medical needs.

What’s coming next:
• Three CGT TRACS publications are expected to be released in the coming months, with several more later this year — stay tuned!
• Throughout our 10 year anniversary, we’ll be featuring committee accomplishments and highlighting the impact CGT TRACS has had on the field over the past decade. Watch this space!

Get involved — new opportunities:
We currently have three new projects in scoping, with opportunities to contribute. If you’re interested in:
• Improving the safety of invivo CAR T therapies (and other engineered cells)
• Advancing safety approaches for invivo gene editing
• Exploring the use of organoids to assess safety and efficacy of CGTs
we’d love to hear from you.

Learn more in the CGT TRACS Fact Sheet: https://connect.hesiglobal.org/H3UKnA

Interested in getting involved? Reach out to Lucilia Mouries and Dominick Laddy to connect with the committee.

HESI Global is pleased to congratulate James Alper Alcaraz, University of Ottawa, on receiving the 2026 EMGS Emerging Scientist Award at the Genetic Toxicology Association Annual Meeting, held May 6 to 8, 2026. The GTA Annual Meeting brings together experts across sectors to share advances in genetic toxicology, including emerging methods, risk assessment approaches, and applications of new technologies.

James supports both the HESI Global Emerging Systems Toxicology for the Assessment of Risk (eSTAR) Committee and the Genetic Toxicology Technical Committee Error Corrected Sequencing work, contributing to collaborative efforts that advance the science and application of innovative tools for safety assessment. His recognition reflects the importance of supporting emerging scientists who are helping shape the future of genetic toxicology and translational safety science.

Please join HESI Global in congratulating James on this well-deserved achievement.

Learn more about the 2026 GTA Annual Meeting: https://gta-us.org/2026-GTA-Annual-Meeting

We are pleased to share that members of the HESI Global Environmental Epidemiology for Risk Assessment Committee, Dr. Igor Burstyn, Mr. David Miller, and Ms. Stephanie Kuhn, are serving as guest editors for a special issue of Global Epidemiology titled “Quantitative Bias Analysis and Sensitivity Analysis: Innovation and Case Studies.”

This special issue will highlight methodological advances and applied examples of quantitative bias analysis (QBA) and sensitivity analysis in epidemiology. The guest editors invite submissions that showcase innovative approaches, practical applications, and real-world case studies.

The submission deadline is March 1, 2027. The call for papers and additional information can be found HERE.

We encourage you to contribute and help advance the use of these important methods in epidemiologic research!

HESI Global’s Targeted Protein Degrader Safety Committee is pleased to share a new publication in Nature Reviews Drug Discovery: “Safety considerations for cereblon-recruiting targeted protein degraders.”

Targeted protein degraders offer exciting potential for treating difficult disease targets, but they can also unintentionally degrade off-target cereblon neosubstrates, creating important safety concerns, including possible toxicity and teratogenic risk. This publication highlights the need for rigorous, consistent approaches to evaluating these risks.

The authors review key aspects of cereblon biology, explore safety considerations for CRBN-recruiting degraders, and suggest best practices for monitoring on-target and off-target degradation. This work supports safer, science-based development of innovative therapies and reflects HESI Global’s mission to collaboratively address global health challenges through cross-sector scientific engagement.

Read the full paper here: Garside et al., 2026. Safety considerations for cereblon-recruiting targeted protein degraders. Nature Reviews Drug Discovery. https://rdcu.be/femcA

Learn more about the Targeted Protein Degrader Safety Committee here: https://hesiglobal.org/targeted-protein-degrader-safety/

HESI Global’s Genetic Toxicology Technical Committee (GTTC) Nitrosamines Research Program is pleased to share a new publication in Mutagenesis: “Nitrosamine Ames Data Review and Method Development: proceedings of a US FDA/HESI workshop.”

The paper summarizes outcomes from a 2024 workshop co-organized by US FDA and HESI Global to optimize Ames test conditions for the evaluation of nitrosamines.

Key highlights:
• Ames test data generated by HESI GTTC, US FDA/NCTR, and EMA’s Mutamind were reviewed
• Recommendations and consensus points on key conditions that influence sensitivity, including metabolic activation, bacterial strains, solvents, and positive controls
• Results from all three research efforts confirm that Ames test conditions are more sensitive for detecting nitrosamines than the standard Ames test protocol
• Identified areas for continued research to support more harmonized, fit-for-purpose safety assessment approaches

Read the full publication here: Atrakchi et al., 2026. Nitrosamine Ames Data Review and Method Development: proceedings of a US FDA/HESI workshop. Mutagenesis. https://doi.org/10.1093/mutage/geag011

Learn more about the Genetic Toxicology Technical Committee here: https://hesiglobal.org/genetic-toxicology-gttc/

HESI Global is pleased to share a new publication from its Cardiac Safety Committee, “Advancing nonclinical blood pressure assessment: Current practices and future directions in drug development,” published in Regulatory Toxicology and Pharmacology. The paper highlights how nonclinical models can help identify drug-related blood pressure effects and support safer decision-making in development.

This work matters because even modest changes in blood pressure can have important clinical consequences, yet blood pressure regulation is complex and can be difficult to translate from nonclinical studies to humans. The publication reviews current approaches, outlines translational challenges, and introduces a HESI Global multi-site study showing consistent blood pressure findings across laboratories in the standard telemetered dog model. These findings will be published separately and support the model’s value for evaluating blood pressure liability in drug development.

Read the full publication here: Pugsley et al. 2026. Advancing nonclinical blood pressure assessment: Current practices and future directions in drug development. Regulatory Toxicology and Pharmacology. https://doi.org/10.1016/j.yrtph.2026.106098

Learn more about HESI Global’s Cardiac Safety Committee here: https://hesiglobal.org/cardiac-safety/

Biologic therapeutics, including monoclonal antibodies, are increasingly important tools in modern medicine. For patients who are pregnant or may become pregnant, understanding how these therapies may transfer across the placenta is essential for interpreting developmental toxicity studies and informing human safety assessments.

A new publication from the HESI Global Developmental and Reproductive Toxicology (DART) Technical Committee provides important insights into this question. Published in Birth Defects Research, the paper, “Ontogeny of Placental FcRn Protein During Human and Animal Pregnancy to Inform Developmental Toxicity Testing,” reports findings from a collaborative, multi-sector experimental program focused on the neonatal Fc receptor (FcRn).

FcRn plays an important role in the transfer of Fc-containing biologics across the placenta during pregnancy. By mapping FcRn protein expression across multiple species and throughout gestation, the research provides new data to help scientists better understand placental transfer of these therapeutics. These findings may improve the interpretation of nonclinical developmental toxicity studies and support more informed human safety assessments for biologic medicines used during pregnancy.

Read the full publication: Bowman et al., 2026. Ontogeny of Placental FcRn Protein During Human and Animal Pregnancy to Inform Developmental Toxicity Testing. Birth Defects Research. http://dx.doi.org/10.1002/bdr2.70058

Learn more about the HESI Global DART Technical Committee: https://hesiglobal.org/developmental-and-reproductive-toxicology-dart/

HESI Global is pleased to share a new publication from the Botanical Safety Consortium, “A screening strategy for identifying the developmental and reproductive toxicity potential of botanicals,” published in Pharmaceutical Biology.

Botanicals are widely used in dietary supplements, cosmetics, and traditional medicines, but their safety can be difficult to evaluate because they are chemically complex and variable. Developmental and reproductive toxicity, or DART, is an important endpoint because effects may involve fertility, pregnancy outcomes, fetal development, or postnatal growth.

To address this challenge, the Botanical Safety Consortium DART Working Group developed a strategy to evaluate a battery of New Approach Methodologies, or NAMs, for screening botanical extracts. The paper describes complementary tools, including stem cell assays, zebrafish embryos, Caenorhabditis elegans, transcriptomics, pharmacology profiling, and selected in silico tools.

This strategy provides a foundation for future testing of integrated NAMs for botanical safety assessment, supporting more efficient screening while helping reduce reliance on mammalian models.

Read the full article: Mahony et al., 2026. A screening strategy for identifying the developmental and reproductive toxicity potential of botanicals. Pharmaceutical Biology. https://doi.org/10.1080/13880209.2026.2659421

Learn more about the Botanical Safety Consortium here: https://botanicalsafetyconsortium.org/

HESI Global’s Genetic Toxicology Technical Committee (GTTC) is pleased to share a new publication in Environmental and Molecular Mutagenesis: “Benchmark Response Values for Error-Corrected Sequencing Mutagenicity Assessment Technologies.”

The paper advanced mutagenicity risk assessment with standardized benchmark response (BMR) for error-corrected sequencing (ECS) technologies.

Key Points:
· Introduces evidence-BMR values tailored to advanced ECS technologies used in mutagenicity testing.
· Finds consistent variability across experimental conditions, supporting use of standardized, technology-specific BMRs.
· Recommends a ~30% BMR as a robust default for in vivo ECS-based mutagenicity assessments.
· Enhances confidence in dose–response modeling and strengthens applications in human health risk assessment and regulatory decision-making.
· Supports integration of next-generation sequencing tools (e.g., Duplex Sequencing, Hawk-Seq) into quantitative toxicology frameworks.

Read the full publication here: Mulugeta et al., 2026. Benchmark Response Values for Error-Corrected Sequencing Mutagenicity Assessment Technologies. Environmental and Molecular Mutagenesis. https://doi.org/10.1002/em.70051

Learn more about HESI Global’s GTTC here: https://hesiglobal.org/genetic-toxicology-gttc/

HESI Global’s recent Benchmark Dose (BMD) webinar and breakout workshop brought together a highly engaged global community to explore the future of BMD modeling in risk assessment. The webinar drew 829 participants from 44 countries, representing both public and private sectors and a broad range of experience levels. This strong participation reflected widespread interest in BMD modeling.

The subsequent expert breakout workshop convened 49 international subject matter experts from the public and private sectors for in-depth discussions across key topics, including benchmark response (BMR) selection, when to apply BMD analysis, study design, Bayesian vs. frequentist approaches, and model selection vs. model averaging.

Across both events, discussions focused on key challenges, including differences in methods, data quality, and regulatory expectations.

Overall, there was strong alignment around the need for fit-for-purpose frameworks, improved study design, and better integration of statistical and biological considerations. Additionally, discussions highlighted clear opportunities for continued collaboration, training, and guidance development within a multi-sector, international group. The BMD Workshop Steering Committee is actively working to summarize discussions and develop a path forward for future work within HESI Global.

Webinar Recordings available:
Day 1: https://www.youtube.com/watch?v=ADuYHodnvBs
Day 2: https://www.youtube.com/watch?v=d9g698UMm90

For questions about the BMD program, please contact Drs. April Kluever and Claire O’Brien.

At IMMUNOLOGY2026 in Boston, MA, the HESI Global Immunosafety Technical Committee (ITC) advanced immune safety science through scientific programming, outreach, and collaboration. A key highlight “Bridging Immunology and Drug Safety: A New Paradigm,” a symposium sponsored by HESI Global that explored the evolution of immunotoxicology, the impact of emerging therapeutic modalities, and the need for innovative, integrated approaches to immune safety assessment and regulatory science.

The ITC also hosted an exhibitor session, “One Target, Many Risks: Immunosafety Challenges from Mechanism to Medicine,” which featured case studies demonstrating how disease context, mechanism of action, and patient population can influence immunotherapy safety profiles. Discussions emphasized the value of mechanistic immunology in predicting adverse responses and informing safer therapeutic design.

In addition, HESI Global Program Managers Chrissy Crute and Shermaine Mitchell-Ryan represented the ITC at the HESI Global booth, where they promoted committee initiatives and fostered new collaborations. Across the meeting, the ITC reinforced its leadership in advancing collaborative, mechanistically informed approaches to immune safety.

HESI Global and NC3Rs recently convened a virtual workshop on NAM Integration for Endocrine Activity. The workshop brought together experts from academia, government, industry, and nonprofit organizations to explore how new approach methodologies (NAMs) can support screening for estrogen receptor agonism activity.

Building on discussions from the Innovate EcoSafety Summit, participants used real-world-inspired chemical datasets to evaluate how different lines of evidence, including in silico, in vitro, mammalian, eleutheroembryo, and in vivo fish data, could be integrated into a transparent weight-of-evidence framework.

Discussions highlighted the importance of concordance across biologically relevant data streams and the value of models, such as eleutheroembryo models, that reflect integrated biology. Participants also explored the challenges of interpreting negative or discordant NAM results, extrapolating across species, and integrating mechanistic data in a regulatory context.

Outcomes from the workshop will help inform continued efforts to develop practical, confidence-based approaches for integrating NAMs into endocrine activity assessment.

The HESI Global Genetic Toxicology Technical Committee (GTTC) brought members together for its annual meeting on May 3 to 5. The meeting featured updates from GTTC working groups, discussion of ongoing scientific initiatives, and opportunities to connect across the genetic toxicology community.

This year’s meeting was especially meaningful as GTTC celebrated the 20th anniversary of the founding of the group that ultimately became the committee. The meeting also marked a leadership transition, as outgoing public co-chair George Johnson concluded his term. In keeping with what has become a GTTC tradition, the committee celebrated his contributions with an honorary bobblehead. GTTC also welcomed Francesco Marchetti as the incoming public co-chair.

Following the annual meeting, GTTC kept the momentum going with a strong presence at the Genetic Toxicology Association (GTA) 2026 meeting on May 6 to 8, continuing what members often refer to as “Genetox Week.” HESI Global managers Connie Chen, Alex Taraboletti, and Raechel Puglisi attended GTA alongside numerous GTTC members who presented data, joined scientific discussions, and represented the committee’s ongoing collaborative work.

Together, the back-to-back meetings provided a great opportunity to reconnect, share progress, and celebrate the continued impact of GTTC’s science, partnerships, and community.

Drs. Michelle Embry, HESI Global Deputy Director, and Doug Wolf, WolfToxRisk LLC and former HESI Global Board of Trustees member, led a one-day interactive workshop at NSF International in Ann Arbor, MI, on Friday, May 8.

The in-person workshop, “Risk assessment in the 21st century (RISK21): A Practical Framework for Risk Assessment,” was attended by 20 participants, including NSF International staff and members of the NSF International Health Advisory Board (HAB).

The workshop featured small-group, hands-on case studies, along with demonstrations of the RISK21 approach and web tool.

The Immunosafety Technical Committee Business Meeting will take place on Wednesday, May 20th, immediately following the NAMs Workshop at HESI Global’s Washington, DC, headquarters. This important gathering will provide committee members with the opportunity to reflect on ongoing initiatives, discuss strategic priorities, and chart the path forward for the committee’s future activities.

Topics to be addressed during the meeting include:
• Updates on current ITC workstreams and collaborative initiatives
• Strategic planning and future committee priorities
• Emerging scientific and regulatory opportunities in the field
• Committee leadership transitions and engagement opportunities
• Discussion of upcoming workshops, partnerships, and deliverables

A special highlight of this year’s meeting will be a tribute honoring our longtime Committee Chair, Dr. Curtis C. Maier (GSK). Dr. Maier has been a dedicated member of the committee since 2007, providing exceptional leadership, insight, and vision throughout his tenure. His steady guidance and influential voice have helped shape the direction of the committee and advance meaningful progress within the field. We are deeply moved by his many years of service, commitment, and unwavering dedication to the ITC community.

As we say goodbye to one legend, we are equally excited to welcome another. We are pleased to extend our enthusiastic congratulations to our new Private Sector Chair, Dr. Mark Collinge (Pfizer). Having already led several key committee workstreams, Mark brings a wealth of experience, energy, and leadership to this new role. While adding yet another responsibility to his growing list of ITC contributions, we are confident that his continued dedication and vision will help propel the committee to even greater heights in the years ahead.

The Eco-NAMs Webinar Series aims to present the most informative and up-to-date science on new approach methodologies (NAMs) for ecotoxicity assessments. Each webinar will consist of presentations by experts followed by a discussion period. The webinar series will provide an open forum for scientists from academia, industry, non-government organisations, regulatory authorities, and other interested parties, including the public, to learn about and discuss various ecotoxicity NAMs topics.

The third webinar in the Eco-NAMs series on the use of NAMs in regulatory ecotoxicology will cover in silico approaches to replace acute fish toxicity. The webinar will be held on Thursday, 28 May, 2026, at 8:00 a.m. EST. Registration and more information are available at https://livewebinar.com/insilicoapproachestoreplaceacutefishtoxicitytesting

The webinar will feature presentations by Anna Lombardo, researcher at Istituto di Ricerche Farmacologiche “Mario Negri” and Paul Thomas, President, Model Developer and Expert Ecotoxicologist at KREATiS.

Ms Lombardo will present a brief introduction to Quantitative Structure Activity Relationships (QSARs) and read-across methods, and then discuss the use of the VEGA (Virtual models for property Evaluation of chemicals within a Global Architecture) HUB tools to assess fish acute toxicity. Through case studies focused on fish acute toxicity that can also be applicable to other endpoints, she will explain the read-across approach used in VERA, the QSAR models available in VEGA, and JANUS, which is a tool for screening and prioritization.

Dr Thomas will discuss the use of mechanistic QSARs for acute fish toxicity prediction, providing background information on the published structural alert scheme, mechanism of action (MechoA), addressing frequently asked questions. His presentation will demonstrate how the method can link toxic effects between different species and acute and chronic exposure using a robust mechanistic approach.

The Eco-NAMs webinars are held quarterly. Links to past webinars will be available at https://www.thepsci.eu/eco-nams-webinars/. The webinar series is co-organised by the European Medicines Agency, the Health and Environmental Sciences Institute, the National Institute for Environmental Studies (Japan), PETA Science Consortium International e.V., the US Environmental Protection Agency (US EPA), and the US Food and Drug Administration (US FDA).

Disclaimer: The views expressed in this webinar series are those of the presenters and do not necessarily represent the official views or policies of the US government, the EMA and the NIES. The US FDA, US EPA, EMA and NIES involvement in this webinar series does not imply official endorsement of, or responsibility for, the opinions, ideas, data, products, or services presented.

Guidance for troubleshooting in LiveWebinar can be found at the bottom of the
Eco-NAMs webinar series webpage.

Join the HESI Global Botanical Safety Consortium for an upcoming webinar on translating in vitro findings to in vivo outcomes.

Dr. Yitong Liu of the U.S. Food and Drug Administration will present: “Translating in vitro mechanistic findings to in vivo toxicity outcomes: A case study of Usnic acid hepatotoxicity.”

Thursday, June 11
10:00 AM ET
Virtual webinar

This presentation will highlight recently published work using quantitative in vitro to in vivo extrapolation, supported by physiologically based pharmacokinetic modeling, to connect mechanistic in vitro data with real-world toxicity outcomes.

Registration is free and open to all, but required.

Learn more and register on the event page: https://botanicalsafetyconsortium.org/bsc-webinar-liu-06-11-2026/

Gene and cell therapies, including AAV-mediated gene transfer, gene editing, and LNP-mRNA platforms, are transforming medicine while raising complex questions around developmental and reproductive toxicity (DART) and germline transmission risk assessment. These issues will be discussed during a two-day workshop later this Fall, co-organized by the Developmental and Reproductive Toxicology (DART) and Cell and Gene Therapy – TRacking, Circulation and Safety (CGT-TRACS) Committees. On 29 – 30 September, experts from industry, academia, and global regulatory agencies to share best practices, review case studies and emerging tools, and identify gaps and harmonization opportunities.

The agenda has been added! Please visit the workshop event page HERE.

Registration will open in June. In-person and virtual attendance will be limited.

For more information or questions, contact Dr. Connie Chen (cchen@hesiglobal.org).

The Health and Environmental Sciences Institute’s Genetic Toxicology Technical Committee (HESI GTTC) Education and Science Outreach Committee is pleased to announce that the 2026 award cycle is now open! These awards will provide opportunities for trainees to attend scientific conferences, workshops, or courses, etc., to build core competencies and transferable skills, and/or share their research. Awardees will be invited to GTTC’s 2027 Annual Meeting to learn about the emerging projects and science at HESI and to network with experts in the genetic toxicology field.

Two award categories:

• Professional Development Travel Award – Provides $1,500 USD for travel to attend scientific conferences or workshops.
• Professional Development Training Award – Provides $4,000 USD for travel specific to training courses, cross-lab trainings, etc., to build core competencies and transferrable skills.

Application Deadline: May 31, 2026

Learn more and download the applications here: https://connect.hesiglobal.org/3bqCXK

Calling early career researchers in cardiovascular safety science.

The HESI Global Cardiac Safety Committee is now accepting applications for the 2026 Early Career Seminar Award Series.

This award supports postdoctoral and early career scientists working in cardiovascular safety science or related fields.

Selected awardees will receive:
• $500 USD award
• Invitation to present their research during a public webinar in Fall 2026
• Opportunity to connect with experts in toxicology and safety pharmacology from academia, regulatory agencies, and pharmaceutical companies

This is a valuable opportunity to share your research, build your network, and engage with leaders across the cardiac safety community.

Deadline: 26 June 2026

View the webpage for more details on how to apply: https://hesiglobal.org/cardiac-safety/#earlycareeraward

Do you have an idea that could advance human or environmental health? HESI Global is seeking collaborative scientific proposals that address emerging challenges through innovative, translational research.

Scientists and experts from academia, industry, government, and nonprofit organizations are invited to submit ideas for new cross-sector initiatives that can drive meaningful scientific, public health, and environmental health impact.

More details, including the project proposal form and contact information, are available on our website: https://hesiglobal.org/propose-a-project/

HESI Global’s Cell and Gene Therapy Tracking, Circulation, and Safety (CGT-TRACS) Committee is inviting AAV product developers from industry and the public sector to participate in a technical survey on approaches to assess the risk of germline transmission in AAV gene therapy development.

As regulators continue to request detailed biodistribution data, particularly in gonadal tissues, there is still considerable variability in how PCR-positive findings are interpreted and how follow-up assays are selected.

As an AAV product developer, your experience can help us better understand how these assessments are being approached in real-world development programs, with the goals to:
• clarify current practices across the field
• identify areas of alignment and remaining variability
• support development of a stepwise approach to germline risk assessment
• help inform more harmonized, science-based expectations from global health authorities

By contributing, you will help advance a more informed and efficient framework for evaluating the risk of germline transmission in AAV-based gene therapy products.

Survey link: https://www.surveymonkey.com/r/GRXTG9D

Participants will also have the option to receive updates on this ongoing effort.

For questions please contact HESI Global staff Dominick Laddy at dladdy@hesiglobal.org or Lucilia Mouriès at lmouries@hesiglobal.org

Micro / Mackerel

I cannot take credit for this play on words. In 2023, HESI Global’s Next Generation Risk Assessment Committee held a workshop in Paris in a very creative meeting space. There were two stairwells. One was covered in pictures of microphones. The other had schools of fish (mackerel!) swimming down it. Being a fish workshop, we were, of course, very excited about the fish stairwell.

The event planner at the venue explained that this was meant to represent the two ends of the spectrum when discussing a topic: micro and macro. People who work with me will probably groan, since I do bring this up from time to time in meetings, and they are likely sick of it. But it really resonates with me, and not just because I like fish.

HESI Global’s work excels because we are constantly toggling between the micro and macro (or, in my head, the mackerel). We focus on the specific scientific details of a method, analyzing complex data and diving into the details. But we also step back to consider the bigger picture: how science can be applied and what the global impacts and implications across numerous stakeholders might be. Within any single project, we move between the two, using our microphones to call out to the mackerel. Or something like that.

Can you tell I love working at HESI Global?

Michelle Embry, PhD, HESI Global Deputy Director

Me and Julie Krzykwa in the mackerel stairwell, Paris 2023.