Spotlight on R&D: Inside the World of DMPK
I’ve always been interested in studying various diseases to understand the factors involved in their cause and progression, striving to ameliorate these severe conditions and improve people’s lives. Studying microbiology early on, I was fascinated by viruses and other infectious disease-causing organisms and worked toward developing antiviral vaccines for disease prevention. This led me to research in host immune responses to infectious diseases, as well as dysregulated biologic function involved in metabolic, inflammatory, and autoimmune diseases and cancer. I pursued a career in biotech to develop therapeutics to treat disease, and I enjoy investigating the DMPK properties of small molecule and antibody modalities to improve their design, safety, and efficacy.
At Variant Bio, I work within the R&D team investigating targets identified by our Genomic Discovery team for therapeutic drug discovery and development in areas such as fibrosis and kidney diseases. We implement drug discovery campaigns for small molecules and biologics (antibodies) and advance preclinical programs toward selecting a clinical development candidate. As Associate Director of DMPK, I lead activities profiling and characterizing these molecules to ensure good drug-like properties warranting advancement through the pipeline.
Before joining Variant Bio, I led similar activities at Silverback Therapeutics, where we developed antibody-drug conjugates to systemically deliver tissue-targeted therapeutics for the treatment of cancer and chronic viral infections. Prior to that, I supported novel target discovery for obesity and autoimmune diseases at Novo Nordisk by leveraging advanced mass spectrometry applications. I bring this drug discovery & development experience to Variant’s multidisciplinary team to help build and advance our human-genetics-backed therapeutic pipeline.
Drug metabolism and pharmacokinetics (DMPK) determines how drugs are metabolized, or chemically transformed, and how compounds move and distribute throughout the body. We perform in vitro assays and in vivo studies to evaluate the absorption, distribution, metabolism, excretion, and toxicity of compounds to optimize their design and determine the viability of a drug candidate for use in humans. This DMPK profiling informs how drugs are administered, at what dose and how frequently is needed to sustain adequate concentrations for sufficient time to achieve the intended response, without causing unacceptable toxicity. This directs our efforts to efficiently advance safe and effective compounds into human clinical trials.
The DMPK capabilities I manage internally at Variant Bio and together with external CROs and partners are critical for informing which molecules should be further characterized or developed. Analytical tools, like mass spectrometry, are used to assess the stability of compounds or identify how the drugs are metabolized so that the chemical structures can then be optimized to improve these characteristics. Additionally, PK profiling to measure plasma and tissue concentrations over time of these small molecules or antibodies informs the dosing strategies for the biology team’s efficacy studies.
We have recently expanded our team with the addition of Thomas Bridges, a Senior DMPK Scientist at Variant Bio with a strong background in small molecule drug discovery. Originally trained as a pharmacologist, Tom joins us with over a decade of experience in preclinical DMPK at the Warren Center for Neuroscience Drug Discovery at Vanderbilt University where he supported the discovery, characterization, and optimization of several novel therapeutic candidates for major central nervous system diseases and disorders. Tom will work closely with me and others on the R&D team to help ensure our programs ultimately deliver new, high-quality therapeutic candidates bearing the requisite pharmacokinetic properties for use in patients.
Going forward, I’m most excited about the potential to translate our collaborative research and partnerships at Variant Bio into life-saving therapies. I’m impressed by Variant’s mission and dedication to strong ethics, benefit sharing, and improving health around the world. This motivates me to strive toward discovering and developing therapeutics to positively impact the lives of patients.
