For episode 15 of S³ we’re featuring Octant, a revolutionary new-age biotech startup! Don’t worry if you’re not a bio expert, I’ll break down their approach in plain english.

Alright here’s a quick mental map before you dive into this:

• How Octant makes novel drugs: the tech, how it’s new, specific diseases

• Cells, robots, and human trials, oh my!

• Building a biotech startup: Cofounders backgrounds, founding vs academia, multi-disciplinary science, humanity’s new (actually old) technology

Cofounded by ex-academic turned CEO, Sri Kosuri, and ex-Googler & Dropboxer, President Ramsey Homsany. Let’s dive into Octant

How Octant discovers drugs

Technology breakthroughs enabling Octant

So how does a startup only 6 years old with $115M raised compete with massive biotech companies who make billions in revenue every year?

Technology.

AI is cool and improvements in the non-bio world have been amazing but biology has been seeing new discovery that impacts the core fundamentals as recently as the past decade… The pace of research, innovation, and discovery can be likened to a Pandora's box within another Pandora's box - the extent is simply immense.

Here are the core breakthroughs that Octant utilizes the most.

• CRISPR — the ability to edit DNA sequences

• Next-gen sequencing — the ability to read DNA sequences you’ve edited

• Large data computation & AI — the ability to parse the insane scale of data you’ve edited then read

What’s insane about this is that the aforementioned advancements are practically brand new, CRISPR genome editing ability came out in 2008 and next-gen sequencing came out just a few years prior.

Octant’s vs Big-bio’s approach

“Drug discovery” is the bio-industry term for the process taken to discover potential molecular compounds that can create drugs to alleviate or cure people’s physical problems.

Typically drug discovery is done by identifying a target like a protein or enzyme associated with a specific disease. They then throw a lot of chemicals at it, this is known as high-throughput screening, to see what causes reactions, when they get “a hit” or a reaction they like they test it more in test tubes and in animals.

Octant differs in its approach at every stage of making the cannoli:

1. Big-bio focuses on a known target or existed literature and knowledge related to a disease, Octant instead explores the biochemical pathways and genetic factors of the entire cell to potentially discover novel therapeutics targets.

2. As a result of this, Octant’s version of high-throughput screening is quite a bit higher in volume versus the singular-facet approach big-bio takes.

3. Last, but definitely not least, is how parallel Octant’s approach is: Big-bio takes a linear approach from identification, synthesis, and testing whereas Octant can flow across these stages allowing for an unprecedented level of iteration.

A simple way to understand their approach is how big-bio and Octant approach cellular science: Big-bio picks its specific target within a cell and pours R&D effort into it while Octant introduces gene modifications across an entire cell and observes what takes places, continually iterating chemical input until an effective therapy is found

Octant’s focus: protein misfolding

Sri and Ramsey feel that Octant’s unique platform for drug discovery and therapy creation are currently best suited to tackle 2 common ailments: protein mis-foldings and cellular mutations that cause cancer.

What is protein mis-folding?

Let’s answer that with a quick trip to Ikea.

• You just went to Ikea and bought a bunch of furniture you want to build, proteins.

• You unbox it all and find the instructions, the DNA, and all of the parts needed to make your furniture, the amino acids.

• You find some of the parts and screws are missing, the metaphor begins to breakdown as this rarely happens with Ikea products — you have 2 choices:

  • (a) you simply can’t build the furniture at all

  • (b) you try to hack it together with a sketchy combo of glues, duck tape, and extra plywood you have lying around.

The frankensteined furniture is akin to a misfolded protein. As Ramsey explains in the episode, the cell will still try to build the proteins despite a lack of amino acids and this can cause these misfoldings.

This metaphor is fun but in reality it’s quite serious. Not being able to build your furniture could mean missing vital support structures, leading to structural failures. In cellular terms, this could translate to diseases like Alzheimer's or Parkinson's.

Delving into the cellular domain unveils how protein misfolding causes issues like lysosomal diseases, Parkinson's, and Huntington's Disease. Similarly, sinister mutations can cause cancer. Octant aims to use their parallel, high-throughput discovery technology to find and provide fixes for ailments that are currently unsolved.

Cells, robots, and human trials, oh my!

Octant’s facility

Octant’s current office is in what was previously a print shot, today it’s filled with cellular cold storage, chemistry labs, a synthetic biology incubation space, and a very cool robot named Hypatia.

Hypatia is Octant’s custom built multiplexing masterpiece.

Wait, what is multiplexing? It’s a biotech term that indicates a ton of parallel testing and efficient simultaneous analysis of the compounds being tested.

Listen if you’re reading this and haven’t watched the episode you should at least watch the part with Hypatia, the little carts are so cute and sound like mice!

In the past weeks I’ve filmed with a bunch of biotech companies, and there have been some interesting facility commonalities: they all have cool biotech stuff like various chemicals, bioreactors, and sequencers, but they also all have robots. Why?

Turns out it’s crazy expensive to have post-grads and docs working on tons of manual pipettes, tests, and microscopy that could be run robotically, 24/7. A lot of these systems sort of look similar, but not Octant’s — Hypatia is a unique, bespoke, and impressive machine designed to help them test and read billions of biological combinations.

Cephalopod culture

The pirates over at Octant truly embrace startup culture. Why are they pirates? Because octopuses, their mascot, have a nuatical theme. Why an octopus? Because it sounds like Octant. Why is it named Octant? Because octant’s were the cheaper versions of sextant’s which were humanity’s first tools developed to discover and understand the stars in our sky.

“Galaxies, upon galaxies, upon galaxies… That happens in the other direction too, your body is made of trillions of cells.” Ramsey described in the episode. There are trillions of cells in your body, each cell is often likened to have a complexity that rivals a massive city like New York which I’m currently landing in ironically. Okay, yes, I had my laptop out during landing, sue me.

Octant’s team is full of young and exciting bio folks who love to be moving at a speed that is decidedly non academic. How do we know they’ve been moving fast? Well, in just 6 years they have 2 drug programs nearly ready for human trials.

Octant’s first drugs

Octant has 2 programs that are just about ready for human trial. This is insane when you remember how new Octant is and how little capital they’ve raise to bring these therapeutics to trial.

The drug their most excited about rescues misfolded rhodopsin genes, when misfolded they lead to retinitis pigmentosa which causes a slow and brutal onsetting of blindness. Since the onset of the program Octant has tested around ~250,000 custom compounds using their high-throughput platform.

We’re looking forward to staying up to date as they plan to begin human trials for their retinitis pigmentosa therapeutic and others that are yet to be announced.

Building a biotech startup

Sri’s UCLA lab and Ramsey’s big-tech background

Before cofounding Octant, Sri and Ramsey had very different backgrounds. Both studied differing degrees of biology in college but after graduation Ramsey went on to have an illustrious career at Google and Dropbox while Sri ran his own lab at UCLA.

One day, after leaving a previous biotech startup, Sri called up Ramsey to discuss founding a new company together. Ramsey was as excited as Sri was. They both felt they had a novel approach, good ideas to build a new biotech company with, and that the underlying biotech was ready for their ambitions.

Multidisciplinary science

“Sri and I believe in this idea of multidisciplinary science,” Ramsey said as he continued to explain their belief that truly innovative work can’t be done within the confines of traditional fields.

Essentially, they want to throw biologists, chemists, data scientists and more into a room and see what happens. It’s a similar approach to their idea of testing different compounds within the cell itself rather than going after a specific tact.

Given their speed of discovery and testing, it’s clearly working. Octant is also practicing what they preach as their company contains chemistry, synthetic biology, robotics, and advanced computation all under one roof.

Humanity’s new (and old) technology breakthrough

When describing his reasoning for going back to biotech and leaving the world of big-tech, Ramsey explained what excited him so much about the field, “This notion that you could actually tap into the life systems around us … it was just very clear to me that we were getting this new access to what is clearly the most powerful technology on the planet, it made the planet, and as humans we’re finally getting access to this technology stack.“

I love that quote. “It made the planet,” is so such a wonderful and mysterious truth that we have so much more to learn from — Sri talked about this idea as well, “Biology is an almost alien technology: we compute, we walk around, we self replicate... It does these amazing things we can’t do in any other form of engineering.”

Sri went on to say, “It’s an engineering discipline waiting to be unlocked.”

I’m going to retype that.

“It’s an engineering discipline waiting to be unlocked.”

I don’t know about you, but I’ve never thought of biology as an engineering discipline. A lot of new biotech founders do but whoah, imagine what we could build if we fully understood and could harness the capabilities of biology?

At the end of the episode, Sri explained that if you want to make real products to impact patients you need to build a company, you can’t do it in academia. Rather than do develop this system in the big bio ecosystem, Sri and Ramsey have opted to build their own ship and sail the sees of biology, navigating with their octant and the stars — and it’s incredibly inspiring to watch.

Thank you for reading, watching, and supporting S³. A big thank you to Octant and team for agreeing to do this.

Keep on building the future,

— Jason

Filmed in Oakland, CA | Edited in San Francisco, CA | Composed in Davis, CA | Written in Boston, MA & New York, NY