New company uses AI and synthetic biology to decode disease-resistance mechanisms evolved across animal species and develop new human therapeutics
BOSTON — Evan Appleton, Ph.D., first and co-corresponding author of a recently published Nature Methods paper describing the first successful derivation of elephant induced pluripotent stem cells, has co-founded Intertwined Biosciences, an AI-native drug discovery company decoding disease-resistance mechanisms evolved across resilient animal species to develop regenerative medicines for humans.
The elephant research, published during Appleton’s tenure as principal scientist at Colossal Biosciences, solved a problem that had gone unsolved for close to two decades. Elephants diverged from the lineage leading to mice and humans roughly 100 million years ago, and conventional reprogramming methods had repeatedly failed on their cells. Appleton and his collaborators developed two new reprogramming approaches, generating stable elephant iPSC lines capable of differentiating into nerve, heart and liver cells.
The work also opened new ground on a longer-standing question: why elephants develop cancer far less often than their body size and lifespan would predict. Other species carry their own protective traits, including naked mole-rats, which resist cancer and age-related decline; bowhead whales, which remain healthy past 200 years; and horses, which rarely develop liver failure. Over hundreds of millions of years, animals have evolved mechanisms to resist cancer, chronic inflammation, aging, fibrosis and organ failure.
Those observations form the scientific foundation of Intertwined Biosciences, which was founded on the premise that evolution represents one of the largest untapped datasets in medicine. The company is building an AI-native discovery platform to identify naturally evolved protective mechanisms, determine which can function in human biology and engineer them into regenerative therapeutics.
At the center of the platform is the Virtual Immune Cell, a generative AI system purpose-built for biological discovery. It integrates comparative biology, genomics, evolutionary evidence, and experimental data to rank millions of potential interventions, design experiments, interpret results, and improve as new data comes in. Predictions get tested in programmable human organoid systems built on more than 15 years of organoid engineering research, which means candidate therapies can be evaluated directly in multicellular human tissue.
Intertwined’s first therapeutic focus is advanced liver fibrosis and cirrhosis, where no approved therapy reverses advanced disease. The same innate immune dysfunction that drives liver fibrosis also contributes to disease in the lung, kidney and heart, and the company expects its platform to generate therapies across those areas as well.
“Evolution has been running experiments on disease resistance for hundreds of millions of years,” said Evan Appleton, Ph.D., Co-Founder and Chief Scientific Officer. “We now have the tools to systematically study those mechanisms across species and determine which can be translated into human medicine.”
“Artificial intelligence has transformed our ability to understand biology, but most AI systems are trained on an incredibly narrow slice of it,” said Max Rye, Co-Founder and Chief Executive Officer of Intertwined Biosciences. “Nature has already performed millions of evolutionary experiments. We’re building an AI-native platform that can read those experiments, understand the biology behind them, and translate the protective mechanisms evolved by resilient species into entirely new medicines.”
Appleton co-founded Intertwined Biosciences alongside Max Rye, Co-Founder and Chief Executive Officer, and Jenhan Tao, Ph.D., Co-Founder and Chief Technology Officer. Together, the founding team combines expertise spanning comparative biology, artificial intelligence, synthetic biology, and regenerative medicine. The company is further supported by a scientific advisory board that includes George Church, Ph.D.; Chris Glass, MD, Ph.D.; Vera Gorbunova, Ph.D.; Tom Knight, Ph.D.; and Douglas Densmore, Ph.D.
Intertwined Biosciences is currently operating in stealth from LabCentral in Boston’s Kendall Square, where it is developing one of the first AI-native drug discovery platforms purpose-built for comparative biology, combining large-scale evolutionary datasets, generative AI, synthetic biology, and programmable human organoid systems to unlock naturally evolved disease-resistance mechanisms and translate them into regenerative medicines.
About Intertwined Biosciences
Intertwined Biosciences decodes the traits that let resilient animals resist disease and engineers those mechanisms into human medicine. The company pairs its Virtual Immune Cell discovery model with programmable human organoid systems to find and test therapeutic interventions faster than conventional drug discovery allows. To learn more, visit intertwined.bio.
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