Edward Larkin
@ealarkin7
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Valius. Palantirian forever.
San Francisco, CA
Joined March 2011
In conclusion, this is an incredibly fun time to invest and operate in diagnostics. ctDNA is perhaps the biggest oncology measurement technology revolution in the last 25 years, and I expect it to meaningfully change the field going forward.
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Additionally, while Signatera is the overwhelming leader right now, it's not a sure thing that they'll win the market. Other companies - especially Guardant - have an interesting angle of attack on the market (Guardant360 moreso than Reveal).
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All this is to say: I'm very optimistic about ctDNA - even moreso than I was a year ago. As I discuss in the piece, that doesn't make investing in it easy - many ctDNA companies are already valued richly, have rallied significantly this year, and are still burning a ton of
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And if we understand it, we stand a better chance of treating it. Even more nascent technologies like cell-free RNA will supercharge these efforts, by highlighting areas where expression changes rather than genetic changes are resistance drivers.
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I expect this trend - assessing the longitudinal genetic changes within ctDNA and treating thusly - to continue. I can imagine a world where cancer patients get ctDNA tests every 1-2 months, not just to assess recurrence, but to understand the mechanisms of resistance.
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This year's SERENA-6 trial at ASCO was the first meaningful step in this direction - instead of just looking for ctDNA levels, investigators repeatedly looked for an ESR1 mutation (common breast cancer resistance mutation), and changed treatment if they found one.
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But perhaps the most exciting part about the future of ctDNA is that increasingly, we're looking for the actual information content of ctDNA (genetic mutations), not just whether tumor DNA exists and at what level.
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The other thing that makes me bullish is on ctDNA tests is that they continue to improve. Going from Signatera (16 variants) to ultrasensitive tests (Personalis has 1,800 variants) meaningfully increases sensitivity. For example, the TRACERx study this year showed that
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Ultra-sensitive tests are better at detecting trace cancer than limited panels like Signatera. And while physicians still have trouble acting on the results (guidelines haven't caught up), this is a good problem to have - I'd rather find recurrent cancer early than late.
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If I was a cancer patient right now, my doctor might order Signatera once every 3-6 months. Signatera is the market leading test with the most evidence. But knowing what I know, I'd probably try to get an ultra-sensitive test (like Personalis, or Signatera Genome), and use them
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But now, I see longitudinal ctDNA testing as a more profound shift in how we measure, track, and treat cancer. Importantly, it's an area where clinical practice can (and perhaps should) outpace clinical trials.
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Link here: https://t.co/T6a0Png5hu A year ago, I thought ctDNA testing (for minimal residual disease in cancer) was simply a big diagnostics opportunity. Most studies found that it caught cancer recurrence faster than imaging. This seemed useful!
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In my most recent post, I dive deep on ctDNA testing and why it stands to profoundly change oncology. This is an area where my own thinking has evolved recently.
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Base by Base Biweekly #8 : June 1, 2025 KJ's gene therapy; OpenAI's diagnostics benchmarks; ctDNA takes over ASCO. And, biweekly market updates. (Link in next post)
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Incredible
CHOP & @PennMedicine have delivered the first-ever personalized gene editing therapy for a patient with CPS1 deficiency, marking a major milestone in the application of CRISPR-based treatments. Learn more about KJ & the future of personalized medicine: https://t.co/A9DTcNmxrR.
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XBI limit down again…
For many years the World has wondered why Prescription Drugs and Pharmaceuticals in the United States States of America were SO MUCH HIGHER IN PRICE THAN THEY WERE IN ANY OTHER NATION, SOMETIMES BEING FIVE TO TEN TIMES MORE EXPENSIVE THAN THE SAME DRUG, MANUFACTURED IN THE EXACT
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Base by Base Biweekly: May 11, 2025 Vinay Prasad named to FDA leadership; Novo teams up with CVS; CGMs move towards mass adoption; Natera's margin question. And, biweekly market updates. Link in next post.
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