Ep171: Ram Aiyar on RNA Editing Medicines

Episode Summary

Executive Summary: Ram Ayyar traces a global, multidisciplinary path from India, Bahrain, and early computer science to biotech operator and CEO. He explains how his experience in data-heavy biology, venture investing, and startup building led him to Coral Bio’s RNA-editing platform, which aims to precisely and reversibly correct disease biology, with a lead focus on alpha-1 antitrypsin deficiency and other CNS and liver diseases.

Main Topics: Global upbringing and formative influences (Priority: 5/5): Ayyar describes growing up across India, Bahrain, the U.S., and Europe, shaped by parents who valued education, a diverse expat environment, and early exposure to sports, electronics, and biology. Training in data-rich biology and computational methods (Priority: 5/5): At Drexel, he worked on neural networks, proteomics, and flow cytometry during the early 2000s, learning to extract signal from noisy, high-dimensional biological data. J&J years and first exposure to translational medicine (Priority: 5/5): He explains how Johnson & Johnson gave him access to real experiments, drug-development thinking, and a chance to contribute to work that later echoed in gene editing and fetal hemoglobin biology. INSEAD, venture capital, and startup formation (Priority: 4/5): Ayyar pivoted to business to understand investing and company-building, then worked in VC in Paris before helping launch multiple biotech startups and becoming drawn to operator roles. Corvidia as a model for capital-efficient biotech execution (Priority: 5/5): He recounts building Corvidia around genetics, inflammation, and cardiovascular disease, emphasizing planning, urgency, and luck, culminating in Novartis’s $2.1 billion acquisition. Why Coral Bio is focused on RNA editing (Priority: 5/5): Ayyar argues RNA editing is better suited than DNA editing for many chronic diseases because it is transient, tunable, redosable, and can address heterogeneous biology without permanent genome changes. Platform potential and future indications (Priority: 4/5): He discusses Coral’s lead alpha-1 antitrypsin program and exploratory efforts in ALS and Parkinson’s, arguing that delivery remains the main limitation but that RNA editing could become a major therapeutic modality.

Key Arguments: Ayyar’s broad exposure to engineering, biology, finance, and startups made him uniquely suited to bridge science and company-building. High-dimensional biological data in the early 2000s created a 'curse of dimensionality,' but also revealed the future importance of computational biology. Corvidia’s success came from combining genetics, longitudinal human data, and validating clinical evidence from external studies before launch. RNA editing is preferable in many chronic diseases because it can be reversible, dose-adjustable, and more appropriate for heterogeneous patient populations than permanent DNA editing. Coral’s platform uses chemically modified RNA and enzymatic machinery to make a precise A-to-I edit, enabling targeted correction rather than gene silencing. Delivery is the central technical bottleneck for RNA therapeutics; the field is advancing by building on earlier oligonucleotide and lipid nanoparticle breakthroughs. Wave’s early alpha-1 data was important because it showed the class effect in humans and de-risked the overall mechanism for the field. Ayyar believes RNA editing will expand broadly over the next decade because a large fraction of transcripts contain adenosines that can be functionally edited.

Data Points: Countries/regions of upbringing: 3 continents - Ayyar says he was born in Mumbai, grew up in Bahrain, then moved to the U.S. and also spent time in Europe. Time in Bahrain: 10 years - He lived in Bahrain from about age 10 after his family relocated there. Time in Mumbai before Bahrain: 10 years - He spent roughly the first decade of life in Mumbai. Drexel graduate study start: 1999 - He began his master’s/PhD work in electrical and computer engineering at Drexel in 1999. J&J-related projects: 2 major projects - He worked on proteomics-based toxicology prediction and epo-agonist differentiation using high-content data. Flow cytometry scale: ~100 million cells and ~20 dimensions - He describes the scale of the J&J/JNJ data challenge in his PhD work. J&J tenure: About 8 years - He says he spent about eight years in total at Johnson & Johnson/Janssen. INSEAD format: 10-month program - He chose INSEAD for its intensive, shorter MBA structure with internships in Singapore and France. Corvidia acquisition value: $2.1 billion - Novartis acquired Corvidia Therapeutics for this amount. Corvidia capital raised: About $100 million - Ayyar says the company raised only about $100 million total. Coral employment start: November 2020 - He joined Coral Bio in November 2020 and had been there for four years at the time of the interview. Alpha-1 product dosing goal: Once-monthly IV infusion - Coral’s first-generation alpha-1 antitrypsin therapy is envisioned as monthly intravenous dosing. Target activity for alpha-1: North of 50% active editing - He says the program likely needs >50% active editing to reach near-normal protein levels. Alpha-1 relevance: 5th most concentrated protein in blood - He uses this to explain why meaningful correction may require substantial protein restoration. Adenosine share of transcriptome: 20–25% - He estimates that a large fraction of RNA transcripts contain adenosines, creating broad potential for editing.

Pivotal Quotes: "I was more hardworking than smart." — Ram Ayyar: He describes his early student years and how he compensated for not being a standout academic. "It was a kid in a candy store, Luke, you know, wanting to come back and have an impact on biology was something that I always wanted to do." — Ram Ayyar: He explains why the chance to do hands-on translational biology at J&J was so energizing. "In my mind, I think delivery is the only thing that limits us in terms of this toolkit." — Ram Ayyar: He summarizes the main remaining barrier to widespread RNA-editing therapeutics.

Implications: RNA editing may become a flexible, repeat-dose therapeutic platform for chronic and heterogeneous diseases where permanent DNA changes are too risky or impractical. If delivery keeps improving, Coral and peers could expand the biotech toolbox substantially.