Genomics Thread #6

Let's talk about liquid biopsies...
1/ A liquid biopsy is usually a blood-based test that can detect cancer.

How?

By detecting either CTC (circulating tumor cells) or ctDNA (circulating tumor DNA). In some studies, ctDNA has been shown to have 100x the concentration as CTC though.
2/ So why is this important?

Well, the standard of care is tissue biopsies. Doctors lop off a piece of the potentially cancerous area (a chunk of your lung for lung cancer for instance) to verify if cancer exists.

However, tissue biopsies are inferior in a few ways...
3/

1. For one, there are more complications. Lung biopsies had a 19% complication rate.

2. They are also expensive, costing nearly $15,000 for each one.

3. They leave a scar and require a surgery

4. It takes a while to get the results

5. Not a lot of tissue can be retrieved
4/ On the other hand, liquid biopsies only require a vial of blood. These genetic tests can profile dozens of genes and determine whether a tumor is malignant.

The main players that already have an approved test are Guardant Health and Foundation Medicine (owned by Roche).
5/ However, many companies are jumping into this space. Because Guardant's LUNAR assay may detect colorectal cancer, Exact Sciences bought Thrive recently for nearly $2.2 billion.

Invitae also bought ArcherDx recently to be competitive.
6/ Guardant Health (GH) has two commercial products, Guardant360 (the world's leading liquid biopsy) and GuardantOMNI for biopharma customers. And two more pipeline products (LUNAR 1 and 2)

Currently, most of the testing is done for NSCLC (non-small cell lung cancer).
7/ Another advantage is that biopharma customers can easily do more testing to see whether their gene therapies are working and if the ctDNA is now less concentrated. That's not really feasible with tissue biopsies.
8/ While Guardant is approved for NSCLC, it is currently trying to use its test for other types of cancer.

To be clear, liquid biopsies won't completely replace tissue biopsies yet. However, there will likely be a "liquid-first paradigm."

If positive, then no need for tissue.
9/ But if negative through the liquid biopsy, there will likely be a tissue biopsy to ensure the diagnosis.

That's not to say liquid biopsies aren't accurate. They are. It's just that very early stage cancer can have very low concentrations of ctDNA.
10/ Besides Guardant, Roche's Foundation Medicine has a diagnostic for prostate cancer or NSCLC patients who might benefit from immunotherapy.

aacc.org/cln/articles/2…

I wouldn't be surprised to see A LOT of new developments in this space in the next few years.
End/ Natera is also working on a liquid biopsy as well as Illumina-owned GRAIL.

In other words, there is a lot of competition but the prize is huge.

Liquid biopsies will enable faster drug production through clinical trials and detect cancer much earlier.

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More from @investing_city

10 Feb
Genomics Thread #7

Let's talk about synthetic DNA...
1/ The leader here is Twist Biosciences (TWST).

Through cutting-edge science and manufacturing, they are able to produce synthetic DNA via a silicon chip.

How is this possible?
2/ It seems like science-fiction but the company can "write" DNA instead of just reading it like a normal sequencing process.

It's called phosphoramidite chemistry.

You can read more about the details here: twistbioscience.com/blog/science/s… Image
Read 11 tweets
3 Feb
Genomics Thread #5

We've already laid the groundwork for understanding DNA, and some parts of the sequencing value chain but now let's talk about genetic testing...
1/ You can think of genetic testing companies as platforms built on top of genome sequencing companies.

Some of the players here are 23andme, Ancestry, Invitae, Fulgent and Natera.

Interestingly, 23andme might come public via SPAC soon: bizjournals.com/sanjose/news/2…
2/ Ancestry and 23andme are probably the most popular DTC genetic testing companies. You receive a test kit, swab your cheek and then you can get insights into your familial history, etc.

However, the DTC market has been more difficult than servicing health care providers.
Read 12 tweets
2 Feb
Genomics Thread #4

Today we're talking about synthetic long-read companies like 10x Genomics and Bionano Genomics...
1/ In the last thread, we discussed the differences between SRS and LRS (go back and read if you need a refresher).

SRS is owned by Illumina and they have brought costs down a crazy amount.

LRS is being pioneered by PacBio and Oxford Nanopore.
2/ But in the past 5 years, there has been a lot of innovation in synthetic long-read sequencing.

The leader here is 10x Genomics.

Broadly speaking, using 10x's Chromium system, researchers can get comparable read lengths at a lower cost than true LRS.
Read 12 tweets
29 Jan
Genomics Thread #3

Let's move onto some companies!

Up first is Pacific BioSciences...
1/ When talking about genomics, the first company that comes to mind for people is likely Illumina.

They really led the charge in short-read sequencing and played a HUGE role in decreasing the overall costs to sequence a genome.
2/ Even now, Illumina has roughly 90% market share in all DNA that has been sequenced. In other words, it's the real giant in this space.

However, the next decade looks more uncertain for Illumina because long-read sequencing is actually superior in some important ways.
Read 16 tweets
28 Jan
Genomics Thread #2

Let's talk about gene sequencing...
1/ The first genome was sequenced in 1977 by Fred Sanger of a bacteriophage.

The first human genome wasn't sequenced until 2003 after 13 years of research through the Human Genome Project.

It took $3 billion (apparently $1 for each base pair 😅)
2/ In the past two decades, the cost of sequencing DNA has declined at an astounding rate.

From $3 billion with the Human Genome Project to well under $1,000 today.
Read 10 tweets

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