Hosted by: The SOT Biotechnology Specialty Section

Beyond MABEL: An Integrative Approach to First-in-Human Dose Selection of Immunomodulators by the HESI Immuno-Safety Technical Committee

Wednesday, October 16, 2024
12:00 Noon to 1:00 PM (US EDT, UTC -4)

Administration of a new drug candidate in a first-in-human (FIH) clinical trial is a particularly challenging phase in drug development and is especially true for immunomodulators, which are a diverse and complex class of drugs with a broad range of mechanisms of action and associated safety risks. Risk is generally greater for immunostimulators, in which safety concerns are associated with acute toxicity, compared to immunosuppressors, where the risks are related to chronic effects. Current methodologies for FIH dose selection for immunostimulators are focused primarily on identifying the minimum anticipated biological effect level (MABEL), which has often resulted in sub-therapeutic doses, leading to long and costly escalation phases. The Health and Environmental Sciences Institute (HESI)–Immuno-Safety Technical Committee (ITC) organized a project to address this issue through two complementary approaches: (i) an industry survey on FIH dose selection strategies and (ii) detailed case studies for immunomodulators in oncology and non-oncology indications. Key messages from the industry survey responses highlighted a preference toward more dynamic PK/PD approaches as in vitro assays are seemingly not representative of true physiological conditions for immunomodulators. These principles are highlighted in case studies. To address the above themes, we have proposed a revised decision tree, which expands on the guidance by the IQ MABEL Working Group (Leach et al. 2021). This approach facilitates a more refined recommendation of FIH dose selection for immunomodulators, allowing for a nuanced consideration of their mechanisms of action (MOAs) and the associated risk- to-benefit ratio, among other factors.

Speakers:

• Mineo Matsumoto, PhD, Reviewer, Review Division, Pharmaceuticals and Medical Devices Agency
• Joseph Ryan Polli, PhD, Clinical Pharmacologist, Pharmacokinetic Sciences and Translational Medicine, Novartis Biomedical Research

Webinar Recording

Hosted by: The SOT Biotechnology and Immunotoxicology Specialty Sections

Understanding the US FDA Guidance on Nonclinical Evaluation of Immunotoxic Potential in Pharmaceuticals: Implications and Insights

Wednesday, January 17, 2024
1:00 PM to 2:00 PM (US EST, UTC -5)

Description: The pharmaceutical industry is constantly evolving, driven by advances in scientific knowledge and regulatory expectations. A pivotal aspect of drug development is the assessment of potential immunotoxic effects caused by pharmaceutical compounds. To provide clarity and consistency in this area, the US Food and Drug Administration (US FDA) released the “Nonclinical Evaluation of the Immunotoxic Potential of Pharmaceuticals” guidance document. This webinar aims to provide the rationale behind the document, elucidate the key elements of this guidance, and engage in a panel discussion about its anticipated impact on drug development strategies. The webinar speaker will focus on the rationale for the document and highlight the scope, objective and key considerations. The following panel discussion will focus on key areas including: 1) Practical implications of the new guidance; 2) Influence on study designs, nonclinical testing strategies, overall drug development process; and 3) Challenges and opportunities for the new guidance. The webinar will then close with a Q&A session with audience members.

Speaker:

• David McMillan, PhD, DABT, Toxicologist, US FDA Division of Pharmacology/Toxicology for Infectious Diseases

Panelists:

• Mary Ellen Cosenza, PhD, DABT, RAC, ERT, Fellow ATS, President MEC Regulatory & Toxicology Consulting LLC
• Florence Burleson, PhD, Executive Vice President, Burleson Research Technologies
• Wendy Freebern, PhD, Senior Director, Immunotoxicology Global Leader, J&J Innovative Medicine

Webinar Recording

Hosted by: The SOT Biotechnology and Food Safety Specialty Section

An Introduction to Precision Fermentation: Application and Challenges

Thursday, October 12, 2023

Description: Precision fermentation is a rapidly emerging technology that promises to revolutionize various industries, from food and beverages to pharmaceuticals and biotechnology. This 90-minute session will provide an in-depth exploration of the science behind precision fermentation, the techno-economic challenges faced by this innovative approach, and the regulatory and safety hurdles that must be navigated for its successful integration into the global market. Furthermore, the session will examine the sustainability outlook and potential challenges associated with implementing precision fermentation on a large scale.

Speakers:

Vincent Sewalt, PhD
Head of Scientific & Public Affairs, International Flavors & Fragrances

Alex Eapen PhD, DABT
Director, R&D Scientific & Regulatory Affairs, Cargill

Adam Leman, PhD,
PLead Scientist, Fermentation, Good Food Institute

Webinar Recording

SOT Biotechnology Specialty Section (BTSS), Ethical, Legal, Forensics, and Societal Issues Specialty Section (ELFSI), and Food Safety Specialty Section (FS3)

Cultivated Meat: Regulatory & Safety Challenges for a Developing Industry

Thursday, February 9, 2023

Description: Description: The development of cultivated meat (e.g., chicken, beef, seafood) holds the potential of solving environmental, ethical, and health challenges associated with the production and consumption of traditional animal-based foods. At the end of 2021, more than 100 companies have emerged across the globe, all aiming to provide meat without slaughtering animals. This emerging technology has, however, raised the need for the rapid development of risk assessment protocols to address the safety of these novel products adequately. In addition, many global regulatory agencies have also found themselves quickly needing to adapt and develop their own regulations to determine how these products can be safely manufactured, distributed, and labeled. This session aims to provide participants with 1) an overview of the molecular methodologies and challenges in the creation of cultivated meat, 2) an examination of the regulatory and safety challenges faced by this novel industry and regulators as well as 3) a brief discussion on consumer expectations on the sustainability, nutritional, and ethical considerations associated with the production of cultivated meat. This session will consist of three presentations followed by a panel discussion moderated by BTSS Secretary/Treasurer René Viñas, PhD, DABT

Speakers:

David Block, PhD
Professor, Department of Chemical Engineering, University of California—Davis

Dave Tonnuci, PhD
Vice President, Regulatory & Toxicology, SciFi Foods, Inc.

Janet Tomiyama, PhD
Professor, Department of Psychology, University of California—Los Angeles

Webinar Recording

Biotechnology Specialty Section (BTSS) and Regulatory and Safety Evaluation Specialty Section (RSESS)

Considerations Regarding Nonhuman Primate Use in Pharmaceutical Development

Thursday, September 22, 2022

Description: Dr. Wange’s presentation focused on approaches to limit the use of nonhuman primates (NHPs) in drug development and will be given in two parts. The first half of the talk provided an overview of the guidance on “Nonclinical Considerations for Mitigating Nonhuman Primate Supply Constraints Arising from the COVID-19 Pandemic,” which was issued as final guidance earlier this year under FDA’s COVID-19 public health emergency authority. The second half of the presentation will focus on alternatives to the NHP for assessing the risks of biotherapeutic proteins to embryofetal and postnatal development. An overview of existing guidance that supports use of alternative in vivo approaches and weight-of-evidence (WOE) analyses for assessing developmental toxicity risk was provided. He also provided an assessment of the degree to which non-NHP sources of information have been leveraged for assessing embryofetal and postnatal development through an analysis of the sources of nonclinical data that have been used to inform section 8.1 of the US product labels for biologics approved by CDER over the last several years.

Speakers: Ronald Wange, PhD
Associate Director for Pharmacology and Toxicology, OND, CDER

Webinar Recording

Biotechnology Specialty Section (BTSS) Webinar

CAR-T Neurotoxicity

Tuesday, February 8, 2022

Abstract: The Biotechnology Specialty Section (BTSS) is hosting a webinar on CAR T-mediated neurotoxicity. Juliane Gust, MD, PhD from the Center for Integrative Brain Research, Seattle Children’s Hospital will present on the clinical manifestations of CD19 CAR T neurotoxicity and discuss whether the concept of Immune Effector Cell Associated Neurologic Toxicity (ICANS) is able to capture the multitude of toxicities that are being described with other products such as bispecific T cell engagers, BCMA CAR T cells, and others. Dr. Gust will review the reasons why neurotoxicity was not anticipated based on preclinical testing, and what progress we have made in our understanding of this toxicity and future strategies for improving preclinical predictivity of immune-system engaging therapies.

Speakers: Juliane Gust, MD, PhD
Acting Assistant Professor, Neurology, Center for Integrative Brian Research, Seattle Children’s Hospital

Webinar Recording

A Biotechnology Specialty Section (BTSS) Webinar (Sponsored by SOT)

How to Choose the Starting Dose for First-in-Human (FIH) Clinical Trials: Principles and Current Use of MABEL

Monday, March 4, 2019

Abstract: Determining the starting dose for the First-in-Human (FIH) clinical trials is a very important aspect of pharmaceutical drug development. There are a variety of approaches that can be used for different therapeutic modalities and indications, and these may vary across industry. This webinar is intended to first provide an overview of different FIH starting dose approaches used in drug development with various therapeutic platforms including small molecules, monoclonal antibodies, antibody drug conjugates (ADCs), and bispecific antibodies for both oncology and non-oncology indications. It would be very educational for students, post-docs, junior toxicologists, as well as study directors who aren’t necessarily exposed to or experience with determining a FIH starting dose. The second part of this webinar will present the results of an industry-wide survey conducted by the IQ MABEL Working Group in 2017 to determine recent (2012–2017) experience by pharma companies using the Minimal Anticipated Biological Effect Level (MABEL) approach for FIH dose selection, which suggests there are some concerns that a MABEL-derived FIH starting dose may be low compared with the eventual desired dose, which in turn may prolong clinical trials and expose patients to sub-therapeutic doses. Recommendations from the IQ MABEL Working Group for selection of the FIH starting dose will be presented, which should be of great interest to pharmaceutical drug developers industry wide.

Speakers: Robert Li, Genentech; Michael Leach, Pfizer

Moderator: Robert Li, Genentech

A Biotechnology Specialty Section (BTSS) Webinar (Sponsored by SOT)

Breaking into the Biotech Industry—Insights for Smooth Sailing

Monday, February 25, 2019

This webinar is designed to provide guidance to graduate students and early career scientists interested in pursuing careers in biotechnology sector. Many candidates have a strong profile, both technically and academically, to pursue industry jobs. However, importance of competent behavioral skills and strong communication skills is often underestimated. While a majority of necessary qualifications are commonly shared between biotech companies and big pharmaceuticals, there continues to be some difference in perspectives of these two sectors. This webinar in Fall 2019 is the 1st part of a 2-Part Career Boosting event sponsored by BTSS. This webinar will be followed by an on-site BTSS Mentoring Event at SOT 2019, Baltimore.

The webinar will cover the following items:

1. Experience & learnings from speakers who have recently (last 1–2 years) transitioned into the biotech sector
2. Importance of networking and ways to establish strong and effective network
3. Importance of developing non-bench skills, leadership roles and volunteering in scientific societies

Speakers: Liz Mutter-Rottmayer, Roivant; Kshama (Doshi) Oza, Surface Oncology; and Amy Shrama, Genentech

Moderator: Mimi Huang, NIH and Co-Moderator: Kshama (Doshi) Oza, Surface Oncology

The BTSS Executive Committee is excited to announce an upcoming webinar entitled, “Predictivity/Translatability of Toxicities Observed in Nonclinical Toxicology Studies to Clinical Safety Outcomes” with talks from four experts in the field (details below).

Date/Time: Friday, February 9, 2018

Abstract:Nonclinical toxicology studies are conducted to characterize the potential toxicities and establish a safe starting dose for new drugs in clinical studies, but the question remains as to how predictable/translatable the nonclinical safety findings are to humans. In many cases, there is good concordance between nonclinical species and patients. However, there are cases when there is a lack of translatability/predictivity that lead to early termination of clinical studies due to un anticipated toxicities or early termination of programs before making it to the clinic due to unacceptable nonclinical toxicities assumed to be translatable. The objective of this session is to better understand safety findings that are translatable versus safety findings that are not and why. Case examples on anti-drug a ntibodies, drug-induced liver injury, bone marrow toxicity and peripheral neuropathy will be highlighted. The desired outcome of this session is to better infor m the future of nonclinical safety assessments for the field of pharmaceutical drug development.

Nonclinical to Clinical Translatability of Bone Marrow Toxicity and Peripheral Neuropathy with Microtubule Inhibitor Containing Antibody Drug Conjugates. Nicola Stagg, Genentech

Reliably Predicting the Toxicity in Humans Based on Nonclinical Studies: Anti-Drug Induced Anemia As a Case Example. Jane Sohn, US FDA

Predicting the Potential of Drug Candidates to Cause Idiosyncratic Liver Injury in Human Patients: Is There Hope? Robert Roth, Michigan State University

Lack of Concordance between Nonclinical and Clinical Findings with Statin Class of Compounds. Kenneth Hastings, Hastings Toxicology Consulting LLC

Best,
Janice Lansita, President, BTSS

Dear BTSS Students and Postdocs,

The BTSS Executive Committee invites you to the annual BTSS Mentoring Lunch at the SOT Annual Meeting in San Antonio this March. This year we are doing things a little different—we have reserved a private room at Rosario’s Southtown to host a mentoring/networking event.

Why should you come? We have set up a very casual environment for you to get to know a few of our members who have excelled in the biotechnology field—from several different employment sectors. The talking points? Whatever you want! We are personally aware of similar events where grad students who clicked with mentors were offered jobs! Not ready to graduate/leave your postdoc yet? Come anyway! The mentors we have lined up are awesome and excited to give you career advice. Plus, you will need to graduate eventually and this is an excellent opportunity to expand your network. Oh, and free lunch!

When is this happening? Tuesday, March 13 from 11:30 AM–1:00 PM.

Where exactly is this at? Rosario’s Southtown, 910 South Alamo Street, San Antonio, Texas 78205 (Yes, it’s not the convention center its better!)

—Your BTSS Executive Committee

A Biotechnology Specialty Section (BTSS) Sponsored Webinar

Navigating From Job Search Through On-Site Interview:
Perspective from Hiring Managers and a Recruiter

Friday, October 6, 2017

This webinar is designed to provide career guidance to early career toxicologists interested in industrial jobs. Many candidates have the technical skills required for an industrial position. However, many are unaware of the recruiting process, resources for searching right job, and what to expect during the conversation with the hiring managers and their team. In the Universities, there are plenty of resources for students who are preparing their CV/resume for academic careers. However, guidance for early career scientists preparing their CV/resume for industrial careers is frequently limited.

Hence, BTSS has organized this webinar with objectives to

1. provide guidance on tailoring a CV, resume, and cover letter to industrial jobs; what a hiring manager will look for in the CV/resume; and how to make a ca tchy resume.
2. provide guidance and resources for a job search in industry. A recruiter will present the process by which recruiters hunt for the right candidates, what they look for in applications, and how candidates should prepare themselves to crack the first barrier.
3. discuss preparation for telephone and on-site interviews, what to expect during these interviews, and what your prospective team is looking for in you.

Speakers: Anne Chester, Gilead Sciences ; Amanda Rose, Battelle ; and Amy Sharma, Amgen

Moderator: Vijay P. Kale, Battelle and Co-Moderator: Joseph Jilek, University of California, Davis

Webinar Recording (Unavailable)

Webinar: BTSS—Careers in Biotechnology for the Toxicologist: What are they and how can I navigate my way to them?

Wednesday, February 3, 2016

Description: Over the past decade, there has been a rapid rise of biotechnology-derived products in medicine, food production, and agriculture; however, many post doctoral fellows and students remain unaware of the diversity of career options for toxicologists in the field.This webinar aims to offer career guidance to the early career toxicologist by promoting a better understanding of career opportunities in risk assessment of biotechnology-derived products across multiple sectors including, private industry, government and academics.

The webinar will consist of a panel of 5 toxicologists; each representing a specific sector of the field (i.e. pharmaceutical industry, academics, consulting, government, and CRO). Each panelist will give an overview of their career path, guidance on how to break into the field, as well as specific attributes needed to do their job well. This will be followed by a 30 minute interactive Q&A session to enable free flowing communication between early and established toxicologists.

Webinar Recording (Unavailable)

Presentation Slides:

2013 Reception
52nd Annual SOT Meeting

Show Me the Bodies…Are GM Foods Safe to Eat
Dr. Alison van Eenennam, UC Davis

2012 Reception
51st Annual SOT Meeting

2011 Reception
50th Annual SOT Meeting