HESI Insights - June / July 2019

HESI welcomed nearly 100 international participants at its 30th anniversary celebration during the 2019 HESI Annual Meeting in Alexandria, Virginia, on 11–12 June 2019. Speakers discussed innovations in multi-disciplinary science, the future of cancer risk assessment, and more. The annual meeting also featured presentations that celebrated HESI’s past, present, and future, including keynote lectures by Dr. Greg Hannon (Cancer Research UK Cambridge Institute) and Dr. Tara Barton-Maclaren (Health Canada). Speakers from the National Toxicology Program, Medicines Evaluation Board, University of Nebraska Medical Center, and more also shared their vision for innovative collaboration across sectors to improve human health and the environment. We thank those of you who joined us at the 2019 HESI Annual Meeting to celebrate 30 years of science for a safer, more sustainable world. To learn more about how HESI science has been implemented around the world to improve decision-making, enhance human health and safety, and preserve the environment, check out the 30th anniversary timeline on our website.

It is our great pleasure to announce that the HESI Cardiac Safety Committee has been awarded a multi-year U01 grant from the US FDA on the “Evaluation of Integrated Human-Relevant Approaches to Identify Drug Induced Cardiovascular Liabilities.” This grant will support HESI in funding and managing novel, in vitro experimental studies to develop targeted mechanistic data to inform drug safety assessment for key cardiac “failure modes.” We expect this program of work will provide a robust complement to the committee’s efforts in this space. Over the coming weeks and months, we will be working with our FDA partners to put together the structure of an advisory team that will consist of expertise both internal and external to this committee. Funded and unfunded participation by a larger community will also be encouraged.

We thank all those who have been part of this process and have contributed their perspectives and expertise to the discussion and specifically to this grant. We look forward to the exciting work ahead!

The grant term starts 1 September 2019 and runs for 3 years pending availability of funding at FDA.

HESI recently partnered with FDA to convene the March 2019 workshop on “Leveraging Human-Relevant Cardiomyocytes in Nonclinical Studies to Provide Mechanistic Insights Into Cardiovascular Safety Liabilities.” The workshop featured experts from the public and private sectors with a variety of experience using human pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) in drug discovery. Speaker presentations as well as the recorded webcast are now available online for review.

On 30 June 2019, the HESI Cell Therapy – TRAcking, Circulation, & Safety (CT-TRACS) Committee co-hosted the Pluripotent Stem Cells Manufacturing Experts Panel Meeting with the California Institute for Regenerative Medicine, (CIRM), the Global Alliance for iPSC Therapies (GAiT), the International Society for Cell and Gene Therapy (ISCT), and the International Stem Cell Banking Initiative (ISCBI). Pre-meeting reading materials, slides, and an audio recording of the event are available via GAiT’s website.

The HESI CT-TRACS Committee is opening a call for participants to form an international multi-site study to test in vitro methodologies for tumorigenicity assessment of cell therapy products (CTPs). The call was announced on June 30, as part of the Pluripotent Stem Cells Manufacturing Experts Panel Meeting in Los Angeles, California.

• Open Date: 30 June 2019
• Application Deadline: 30 August 2019
• Project Start Date: 27 September 2019
  • In-person kick-off meeting at HESI facilities in Washington, DC
• Title: “Predictive Methods to Assess the Tumorigenicity of Human Cell-Based Therapeutic Products In Vitro: A Multi-Site Replication Study”
• Preliminary Materials From the MEASURE Study: Click here for preliminary materials, including presentations from Dr. Keiji Yamamoto (Takeda/FIRM, Japan), Dr. Yoji Sato (NIHS, Japan), and Dr. Takatoshi Koujitani (Sumitomo Dainippon Pharma, Japan).
• Benefits for Participants:
  • Knowledge and know-how: Access preliminary data and protocols from the MEASURE studies; learn from a multi-disciplinary team of experts.
  • Data access: Access new data generated at all sites through this international study.
  • Leadership: Contribute to the study design with your expertise; help guide the evolution to a more data-driven characterization framework, rather than theoretical; and help lead the development of new standardized approaches for CTPs safety evaluation.
  • Authorship: Take part in publication opportunities and fostering open scientific interaction in the public domain.
  • Working group activities: This is an opportunity to benefit from other CT-TRACS working groups’ activities at no extra cost.

Click here to learn more about the study or to express interest. Please contact Lucilia Mouriès (lmouries@hesiglobal.org) with any questions.

On the inaugural United Nations’ “World Food Safety Day” (7 June 2019), HESI and the COMPARE Allergen Database steering team released “COMPASS” (COMPare Analysis of Sequences with Software)! COMPASS is a built-in bioinformatics utility, now available on the COMPARE Database website that allows users to identify similarities between a protein sequence of interest and COMPARE’s allergens. The tool equips the database with the functionality required for allergenicity assessments, applying sequence alignments and comparisons requirements set forth by the FAO/WHO and Codex Alimentarius global guidelines.

To access COMPASS, please visit the COMPARE website.

On 10 July 2019, Jean-Charles Gautier (Sanofi) presented “Urinary miRNA Biomarkers of Kidney Toxicity and Their Site Specificity Within the Renal Nephron: A HESI Consortium Effort” at the Gordon Research Conference on Guiding Drug Development Using Translational ADME Science in Holderness, New Hampshire. Further conference details are available here.

The Immuno-safety Technical Committee (ITC) will hold a workshop in partnership with FDA/CBER in Silver Spring, Maryland, on 24–25 September 2019. The goal of this workshop is to discuss the preclinical and translational safety assessment of engineered T cell therapies. The workshop will focus on six topics, followed by an in-depth discussion:

• Designing engineered T cells for optimal activity and safety
• Target expression and associated liability assessment
• In vivo models informing safety and activity
• Safety of viral and non-viral gene delivery systems—utility, risk of genomic injury
• Linking preclinical development with the clinical experience
• Regulatory considerations

For more information and to register, please visit the website or contact Stan Parish (sparish@hesiglobal.org).

Are you interested in hearing about new science to evaluate bioaccumulation of organic chemicals? Would you like to learn how fish biotransformation can be integrated into bioaccumulation assessment? Do you want to hear about the new OECD in vitro biotransformation fish methods? Would you like to have training and experience using the Bioaccumulation Assessment Tool (BAT)? Plan to attend the HESI Bioaccumulation Committee Fish Biotransformation in Bioaccumulation Outreach Session on 4 October 2019 in Washington, DC. Registration is free! Contact Michelle Embry (membry@hesiglobal.org) for more details.

I had the pleasure of opening the HESI Annual Meeting in June with a retrospective analysis of 30 years of HESI. In anniversary etiquette, the 30^th anniversary is the “pearl” anniversary, so we celebrated with a reminder that it is often an irritation that initiates a pearl, and advanced to including many HESI accomplishments as “pearls of wisdom” or “string of pearls.” It was a fun way to highlight the progress that HESI has made in contributing to scientific advancements, enabling engagement across industry, academia, and government and building an increasingly more global presence. We should be very proud of how HESI has flourished in the past 30 years and the collective impact that the scientific committees and leadership continue to have in enhancing human and environmental science and risk assessment. However, one of the real “pearls” of note is the financial value that HESI has delivered since its inception. In fact, HESI leadership has held corporate dues structure essentially flat for the past 20 years. This stability reflects a concerted effort to improve administrative efficiencies and maintain thoughtful financial stewardship. In contrast, the Bureau of Labor Statistics reports that the consumer price index has increased just over 50% in the past 20 years. To be precise, a $1 expense in 1999 would cost $1.53 today. Importantly, I am pleased to report that at the Board meeting that preceded the Annual Meeting, the Trustees voted to keep the 2020 dues structure at the 2019 levels. There are very few organizations who have the record of delivering professional value, while sustaining this level of financial value and cost effectiveness. That’s truly a real pearl!

Lois Lehman-McKeeman
HESI Chair