On this week's @ARKInvest newsletter (📰), I plan to discuss some exciting research on molecular (prog)nostics. I'm also going to touch on why long-read #sequencing is so important within oncology.
Here's some context:
2/8
We believe multi-cancer liquid biopsy screening will allow dozens of cancers to be detected earlier. However, not all tumors are lethal. Some may never cause symptoms.
By reflexing to surgery, we risk overtreating patients whose tumors may never need it.
3/8
Companies like Veracyte (VCYT) and Castle (CSTL) offer prognostic tests, using a combination of machine learning and gene expression, to risk-stratify suspicious nodules beyond standard cytopathology.
We believe molecular prognostic testing could give physicians a better understanding of a tumor's eventual fate, perhaps reducing the risk of overtreatment. This approach is not a panacea, and there's still much learning to do, but the future looks bright.
5/8
Molecular prognostic tests result from the collision of #MachineLearning and next-gen sequencing, both of which rapidly are becoming cheaper. We think that these tests, even if given annually for decades, should be considerably cheaper than the cost of cancer treatment.
While her work utilized low pass short-reads, I'll note that copy number variants (CNVs) are particularly amenable to long-read platforms (so long as tissue isn't degraded).
Here's another great paper by @mike_schatz and team that discusses this:
In summary, we'll dive into long-reads, prognostics, and other ways to tackle overtreatment throughout the week. Please add any and all questions and I'll try to address them in my weekly newsletter.
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>90% of Americans over 45 have seen a Cologuard ad this week.
Fewer know of the test's parent company, Exact Sciences (EXAS), whose tests also guide care for the majority of early-stage breast cancer patients in the US.
Today, we released a 5-year model + article on Exact.
Our (base case) 2027 price target is $140 ($49 today). To get there, here's what we believe has to happen:
1. Exact's core business (Cologuard + Oncotype DX) grows on avg. >15% per year thru 2027, reaching $4B.
2. Exact achieves EBITDA positivity in the '23/'24 timeframe.
What we believe must happen (Cont.):
3. Exact uses its earnings to reinvest in its burgeoning pipeline, service its outstanding debt, and maintain its capital equipment.
4. Exact's pipeline, in aggregate, hits >$1B revenue by the end of 2027.
Now that @Quantum_Si has given us a peek under the hood of its protein #sequencing platform (Platinum), we can begin comparing actual results to theory.
A few months ago, I shared this paper that gave a theoretical framework for protein sequencing: pubs.acs.org/doi/10.1021/ac…
The author simulated how different factors, such as the # of readable amino acids (AAs) and the read length, would affect a protein sequencer's ability to unambiguously detect the 20,000 canonical human proteins in our bodies.
That chart is attached below.
I've marked in green where QSI currently stacks up. Based on its recent pre-print (linked below), Platinum can directly read seven (7) amino acids (F, Y, W, L, I, V, and R) with peptide reads that seem to max out around 20 AAs.
A recent publication by Dennis Lo et al applied long-read sequencing (LRS) in the prenatal screening (#NIPT) setting. It's a rather unorthodox technology/application pairing, and it's got me scratching my head a bit.
For context, earlier this year, Lo et al published a convolutional neural network ("the HK model") that enabled PacBio LRS devices to read methylation (5mC) across the entire genome with very high fidelity. This is important later.
@MJLBio@Sanctuary_Bio@Biohazard3737 Sure! I realize I was being a little vague with those statements. Generally, I think you're correct in your interpretation of the importance of P2 (great $/GB, but at a smaller scale) as well as duplex sequencing.
Something that is important to recognize, though ...
@MJLBio@Sanctuary_Bio@Biohazard3737 ... is how product deployment works differently between PacBio and Nanopore, which is partly an artefact of culture and of time in the public markets, in the public markets. I'm not advocating for one over the other with my next statements.
@MJLBio@Sanctuary_Bio@Biohazard3737 PacBio has been a public company for a long time. While the management has changed much since the failed Illumina merger, the familiarity with how to operate as a public company has not.
PacBio is more secretive and only unveils fully built-out commercial products.
I'd like to share my initial reaction to today's Berkeley Lights report. But first, I need to do some housekeeping. I can't comment on stock movements, share financial projections, or debate fair value.
Generally, I respect anyone who's put this much work into a topic. I won't pretend to have a clean rebuttal to every point. In my experience, beyond the hyperbole and hasty generalizations, there is some truth in these types of reports.
I want to soberly appraise those truths.
Also, I'd invite the subject-matter experts waiting in the wings to build off of this thread, add detail, or share their experiences. Ultimately, we're all after the same thing.
I will start with a few concessions and end with a few counterpoints to today's report: