Sarah Knutson
Senior Director - Early Discovery Early Discovery ROME Therapeutics
Sarah Knutson, PhD., is an accomplished drug discovery scientist with experience in advancing small molecule therapeutics from target identification to IND filing. Her disease area expertise spans oncology, neurodegeneration, and autoimmunity, with a strong focus on epigenetics and transcriptional biology. In her most recent role at ROME Tx, Dr. Knutson led pre-clinical development of reverse transcriptase inhibitors to target repetitive mobile DNA elements, for therapeutic application in neurodegenerative disease.
Prior to ROME, Dr. Knutson held positions across early-stage biotech companies to develop platforms for target identification, validation, and drug repurposing. Most notably, she served as biology lead for the EZH2 oncology program, contributing to translational biomarker identification, clinical development, and FDA approval of EPZ-6438 (Tazemetostat/TAZVERIK), in multiple oncology indications.
Dr. Knutson received her graduate training at Vanderbilt University, post-doctoral training at Novartis Institutes for Biomedical Research, and has numerous peer-reviewed publications and presentations at scientific conferences.
Seminars
- LINE‑1 retrotransposons can become aberrantly active under stress, contributing to genomic instability and neuroinflammation in ALS
- Selective LINE‑1 reverse transcriptase inhibitors suppress cytosolic LINE‑1 activity and blunt innate immune activation
- Preclinical models show neuroprotective effects, supporting motor neuron survival and reducing pathological signaling
- Translational considerations include biomarker development, CNS delivery, and differentiating selective inhibitors from earlier non‑specific approaches
- How regulatory expectations differ across modalities (oral small molecules, ASOs, viral gene therapies, RNA medicines, cell therapies) and how developers can prepare for emerging FDA/EMA frameworks in ALS
- Which modalities are best suited for distinct ALS biological subtypes, including TDP-43 proteinopathy, C9orf72 repeat expansion, inflammatory/neuroimmune signatures, and mitochondrial/metabolic dysfunction
- Opportunities and challenges for combining modalities—for example coupling gene modulation with neuroprotective small molecules, pairing oligos with smallmolecule chaperones, or integrating metabolic stabilizers with anti-inflammatory approaches
- How modality mechanisms intersect (protein homeostasis, RNA regulation, axonal transport, synaptic resilience) and how cross-mechanistic synergy could inform trial design or biomarker development
- What is needed to run smarter, modality-agnostic clinical trials—harmonized biomarkers (NfL, speech, digital mobility), shared control arms, adaptive designs, and platform/basket approaches
