5 strategic insights from Endura Therapeutics’ CEO

CEO of Endura Therapeutics, Adrian Sanborn, shares his top five insights on how the company's TRANSCEND platform and covalent small molecule approach are making previously inaccessible disease targets druggable for the first time. Read the full story today!

Five insights from Endura Therapeutics CEO Adrian Sanborn on the next frontier in drug discovery

Adrian Sanborn became a scientist when exponential growth in DNA sequencing was reshaping all of biology. He saw the same pattern again and again: convert your question into a sequencing readout, and the data drives a revolution. As CEO and Co-founder of Endura Therapeutics and resident of JLABS San Francisco and San Diego, he is betting that drug discovery is next.

Endura is developing oral small-molecule medicines that target disease-causing proteins at the RNA level, before the protein is ever made. Their covalent molecules leave a targeted chemical scar on RNA that is detectable by sequencing, revealing which RNAs were bound in a cell, at which nucleotides, across the entire transcriptome in a single experiment. This discovery engine, TRANSCEND, transforms drug discovery from a one-target-at-a-time effort into a systematic search.

Drawing on Sanborn's experience as a scientist, founder, and CEO, here are his top five insights on how Endura approaches biotech's most persistent challenges.

1. Human genomics has identified the targets, but the challenge is reaching them

Human genomics has identified clear disease-causing proteins across cancer, neurodegeneration, and rare disease, but the majority still lack an approved drug. Many of these proteins offer no suitable binding site for a conventional medicine. The genetic medicines that can target them upstream, ASOs, siRNAs, and CRISPR, have produced extraordinary results for patients, but they are large molecules limited by tissue delivery, reaching only a handful of organs in the body.

By teaching an oral small molecule to target the genetic message, Endura can address these proteins across tissues that genetic medicines cannot yet reach.

2. The best science comes from combining fields that haven't talked to each other

Covalent chemistry has produced some of the most impactful drugs of the last decade, from BTK inhibitors in blood cancers to KRAS inhibitors in lung cancer. Nearly all of this work has focused on reacting with cysteine residues on proteins, but the covalent toolbox has recently exploded with new warheads capable of targeting other reactive sites. Co-founder Ayah Abdeldayem, Head of Chemistry, is at the cutting edge of this. Her research developing new covalent warheads became the foundation of Dunad Therapeutics. She was among the first to recognize that these same tools could be turned toward RNA.

The founding insight was that the advantages of covalent chemistry were perfectly matched to the key challenges of drugging RNA, and this came from Co-founder and CSO Jeff Rogers. After seven years leading Novartis's RNA Initiative and two years leading a Flagship company to drug RNA, he had tried everything and kept running into the same two problems. Functionally, a protein has an active site where binding predictably disrupts biology, but mRNA has no equivalent; reversible small molecule binding to a coding sequence isn't strong enough to stop the ribosome. Structurally, mRNA is actively remodeled inside cells by helicases and RNA-binding proteins, so the binding sites you find in a test tube may not exist in a living cell. Covalent chemistry solves both problems at once: the chemical scar physically blocks the ribosome, and the bond's permanence allows testing to be done directly in living cells.

Once the people and ideas came together, the founding team had no choice but to start Endura to see it through.

3. The first success in a new field is usually only a fraction of what's ultimately possible

Roche's risdiplam (Evrysdi) demonstrated that a small molecule can achieve genetic precision through RNA, and it has steadily displaced the incumbent genetic medicines for spinal muscular atrophy as patients chose an oral drug they could take at home. But risdiplam works by redirecting splicing machinery at specific splice sites, which represent approximately 1% of any given mRNA.

Endura's covalent mechanism is not constrained by splicing biology. Binding nearly anywhere in the mRNA can be productive, expanding the druggable sequence space by two orders of magnitude.

4. Small molecules can go where genetic medicines cannot, and that matters for patients everywhere

In oncology, many of the most important cancer drivers are proteins like transcription factors that lack druggable pockets or enzymatic active sites, leaving them undrugged despite decades of effort. And while ASOs and siRNAs have proven they can silence targets upstream, they cannot reach solid tumors, so patients with some of the most deadly cancers have no options. Endura's oral small molecules can distribute throughout the body, reaching tumors that large molecules cannot. In neurodegeneration, small molecules are similarly privileged: they can penetrate deep brain tissue that is difficult or impossible for large molecules to reach, offering patients an alternative to the repeated intrathecal injections that current treatments require.

The access argument extends beyond clinical reach. Small molecule pills can be manufactured at low cost, shipped without a cold chain, and taken at home. When patents expire, this is what allows generics to make a medicine accessible worldwide, a path that biologics and gene therapies cannot follow.

5. Follow the data, even when it's uncomfortable

When asked about a book that has shaped his thinking, Sanborn points to "Zen Mind, Beginner's Mind" by Shunryu Suzuki, a classic he has read multiple times, a couple of pages each night. A core Zen tenet is perceiving things exactly as they are, including uncomfortable things you'd rather not face.

As he puts it, "That sounds simple, but it takes surprising effort to truly pay close attention and shed your preconceived notions." For him, this resonates directly with scientific practice, where the whole work is following the data even when it contradicts your assumptions, and equally with building a startup, where unexpected challenges require quickly accepting them as your new reality so you can focus on finding a solution.

That same self-awareness extends to how Sanborn thinks about the demands of the job itself: "Understand what you draw strength from. This job requires giving a lot of yourself, and it can become draining faster than you expect. Prioritize self-care, both for your own well-being and because your team needs you to have the energy to lead well and make good decisions."

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Endura has assembled a scientific advisory board of covalent chemistry and RNA structure experts: Dan Nomura (UC Berkeley), Patrick Gunning (University of Glasgow), and Roger Kornberg (Stanford, Nobel Laureate). To date, TRANSCEND has scaled to collect over three billion data points. Over the next 12 to 18 months, the team will advance its lead programs in oncology and neurology and expand the pipeline by using its platform to identify new druggable RNA targets across disease areas. Endura is supported by top venture funds including True Ventures, Compound, and 8VC.

To learn more about Endura Therapeutics, visit enduratx.com.

To connect with the team at Johnson & Johnson's external innovation group, JLABS, and learn more about what's happening across the entire JLABS ecosystem, visit jnjinnovation.com/connect-with-team or subscribe at jnjinnovation.com/subscribe.