Bola Oyegunwa, Ph.D., MBA, MMB

Bola Oyegunwa, Ph.D., has served as Labcorp’s Executive Vice President and Chief Information and Technology Officer since November 2024.

Graphical Summary: Comprehensive NGS profiling to enable detection of ALK gene rearrangements and MET amplification in non-small cell lung cancer

First report of spontaneous uveodermatologic syndrome in a laboratory beagle dog: Histological and immunohistochemical features

BSTP 2024 -- Canine uveodermatologic syndrome (UDS) is an autoimmune disorder targeting tyrosinase or tyrosinase-related proteins within melanocytes and partially resembling human Vogt-Koyanagi-Harada syndrome. For the American Akita dog breed, a higher risk to develop UDS has related to the dog leukocyte antigen haplotype: (DLA)-DQAI*00201. The syndrome is usually observed at the mean age of 3.6 years, and female-to-male ratio is 0.6 to 1. UDS has not been reported as a spontaneous change in beagle laboratory dogs, although it has been reported as an experimentally induced change in animal models including rats, dogs and monkeys. 

Evaluation of endogenous and ex vivo stimulated matrices for validation of cytokine expression assessment

ACT 2024 -- Elevated concentrations of cytokines indicate activation of pathways associated with inflammation, and the measurement of cytokines has been widely used to understand and to monitor the effects of therapeutic treatments. Validated methods for the evaluation of biomarkers such as cytokines require a biological matrix relevant to the physiology and distribution of the biomarker. The source of the biomarker can potentially influence the validation process and subsequently the robustness of the method. Endogenous nonhuman primate (NHP) cytokine samples and ex vivo stimulated NHP samples [whole blood and peripheral blood mononuclear cells (PBMCs)] were generated and compared to recombinant cytokines. These samples were assessed across kits and assay format for cytokine expression to evaluate the utility of these matrices in validating methods. The NHP endogenous matrix, stimulated matrix and spiked matrix using recombinant material all generated methods that reliably detected cytokines in study samples and demonstrated similar patterns of cytokine expression. While endogenous samples are preferred, it can be difficult to obtain an identical matrix to that of the study samples. The comparison data demonstrate that the cytokine expression in ex vivo generated matrices are acceptable and scientifically appropriate for method validation.

Retrospective analysis of nonclinical regulatory strategy for 13 approved oncology antibody-drug conjugates

ACT 2024 -- Antibody-drug conjugates (ADCs) have been in development for the treatment of advanced stage cancer for over 25 years. Currently, there are 13 approved ADCs that have been approved by FDA and EU. While there are no specific regulatory guidance documents that provide detailed guidance on the nonclinical development of ADCs, several regulatory guidance documents provide a recommended framework for the nonclinical development of ADCs including: ICH S6(R1) Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals, and ICH S9 Nonclinical Evaluation for Anticancer Pharmaceuticals and the associated Questions and Answers Guidance Document. In May 2023, a new guidance, Generally Accepted Scientific Knowledge (GASK) in Applications for Drug and Biological Products: Nonclinical Information, was published by the FDA. We reviewed all 13 of the publicly available pharmacology and toxicology reviews for approved ADCs. Of these 13 ADCs, 7 were products that utilized microtubulin inhibitor payloads and all of these nonclinical safety programs included either stand-alone, payload-only studies or additional dose groups that were administered the payload alone in rats, dogs and/or nonhuman primates (NHPs). Given the robust assessment of microtubulin inhibitors and similarity in toxicological findings of the microtubulin inhibitors in approved ADC drugs and the literature, we propose that developers of novel ADCs could leverage the GASK guidance to develop a rationale for health authorities to replace the need to conduct characterization of previously characterized microtubulin inhibitors. If accepted by regulators, this could accelerate the nonclinical development of ADCs, reduce animal use and bring life-saving medicines to patients faster.

Mouse versus rabbit: Time course of corneal ocular toxicity of an antibody drug conjugate (ADC) with a maytansinoid payload

ACT 2024 -- Microcystic-like epithelial changes (MECs) in the cornea (keratopathy) are a known ocular toxicity risk of antibody-drug conjugates with microtubulin-acting payloads that generally manifest unrelated to antibody target and occur in the absence of corneal target expression. Dutch-Belted rabbits have been utilized for ocular toxicity studies to replicate and investigate presentation, onset and explore prophylactic techniques to mitigate this corneal finding. Here we evaluate if mice are a useful preclinical model for predicting keratopathy and compare the onset, severity and characterization of MECs in rabbits to mice using confocal microscopy and histopathological evaluation.

Inhaled delivery of a selective immune modulator to minipigs produces favorable toxicity profile

ACT 2024 -- OCI-B2 is a potential therapy for COVID-19 through immune modulation allowing B cell stimulation to fight the virus by inhibiting cascades leading to acute respiratory distress syndrome (ARDS). The first-in-human nonclinical safety assessment package was undertaken using the inhaled route. Inhalation delivery directly to lungs is important due to compromised pulmonary circulation in ARDS. Minipig was identified as the most suitable non-rodent species due to metabolic profiling. Favorable toxicology results enabled progression to Phase I clinical trial.

Bridging the Gap: Enabling Equal Access to Biomarker Cancer Testing and Clinical Trials for Black Patients

Advancements in biomarker testing, clinical research and targeted th­­erapies offer personalized treatment plans that can improve patient health outcomes, but Black patients with cancer often do not have access to these breakthroughs in cancer care. Some of the barriers faced by many Black patients with cancer include lack of insurance coverage, medical biases, medical mistrust and lack of awareness. In particular, this survey found that the main barriers were, in fact, a mistrust in the medical system, a fear for safety and a concern about being a “guinea pig” a test subject for unproven therapies without their knowledge or consent. 

Assessment of leading regulatory T cell immunophenotyping methods using flow cytometry

ACT 2024 -- Regulatory T cells (Tregs) are widely recognized as a critical component of the immune system and an increasing number of studies are identifying new roles these cells play in immune tolerance and the success of clinical immunotherapy treatment. Due to the importance of accurately measuring Tregs in the modern drug development landscape, greater scrutiny is being placed on the methods used to identify them. Immunophenotyping via flow cytometry is a widely recognized technique for analyzing Tregs in whole blood from both preclinical and clinical samples; however, the preferred set of markers for identifying Tregs is debated. Here, our laboratory examined three widely used Treg phenotypes (CD25+FoxP3+, CD25+CD127- and CD25+FoxP3+CD127-) in parallel using whole blood from up to 32 cynomolgus macaques, a common nonhuman primate model in toxicological safety assessment studies. 

Comparison of intratracheal and inhaled AAV pulmonary deposition in two species

ACT 2024 -- Cell and gene therapies (CGT) offer an attractive approach to treating monogenic pulmonary diseases. Standard nonclinical inhalation (INH) exposure systems require greater volumes of test article than other parenteral routes of administration because multiple animals are simultaneously dosed on a single exposure system with innate inefficiencies. Because clinical treatment with CGT modalities will likely only require single or infrequent dose administration, intratracheal (IT) administration offers an alternative route for pulmonary delivery; however, IT dosing requires anesthesia. Customized administration techniques for IT administration to cynomolgus monkey (NHP) and nose-only inhalation to mice were set up for delivery of an adeno-associated virus (AAV). Results from the mouse study were presented previously, while here the hypothesis tested is regarding achieved lung doses and test article usage.