I Can See Clearly Now: Seer Creates a Transformative View of the Protein Panorama

If you’re looking at an image of a cell or tissue that’s stained or glowing, there’s a good chance that the signal you’re observing hails from a protein. For years, ligands such as antibodies and fluorescent tags (e.g., GFP) have labeled proteins in space and even time. There are also entire departments devoted to visualizing and deciphering protein structure, an integral component of drug discovery and design. But mass-scale profiling of populations of proteins has remained elusive, unlike genomics and transcriptomics for DNA and RNA, respectively. Until recently, proteomics experiments were limited to analyzing dozens (or at most hundreds) of proteins, typically in a targeted manner.

That’s the entry point for Seer, founded in 2017 by CEO Omid Farokhzad, MD (previously a professor at Harvard Medical School), MIT professor Bob Langer, PhD, and Philip Ma, PhD, which recently went public. The life sciences company, based out of Redwood City, CA, is making unbiased, deep, rapid, large-scale proteomics a reality. Seer provides the scientific community with unprecedented access to analyze protein diversity, potentially unlocking a new era of diagnostics and drug development.

The company’s Proteograph™ suite of products includes optimized reagents and consumables, automation, and software, and integrates seamlessly with nearly all existing mass spectrometers. With this product suite, Seer enables proteomics studies with what it says is an unprecedented combination of speed, efficiency, and data output.

Seer isn’t the only tech company hoping to do for proteomics what Illumina has accomplished over the past 15 years in genomics. But one recent recruit helping their cause is Omead Ostadan, who left Illumina after a distinguished career there to join Seer in the summer of 2020 as president and COO, overseeing the company’s commercial and product launch strategy.

GEN Edge spoke with Farokhzad to discuss how Seer scoped out its approach to next-generation proteomics technology and the proteomics market.

 

GEN Edge: What is Seer’s mission and vision?

Farokhzad: The goal is to empower the scientific community with life science tools to achieve extraordinary scientific outcomes by taking technological barriers off the table to access the proteome. The core aspect of what Seer does is it enables scientists to access the proteome in a deep way, whereas existing technologies only allow access to the proteome through a narrow pinhole, so to speak. Seer’s technology lets you see the broad panorama of the total complexity of the proteome at a scale and speed that was previously not possible.

The genomic and transcriptomics work over the last 15 years has opened up new markets, companies, and applications. The impact has been enormous. In medicine and science, we just haven’t had the same access to the proteome. Seer is addressing this problem by eliminating the obstacles that have kept proteomics’ potential from matching the pace of advancements we’ve seen in other fields. Our mission is to provide solutions for unbiased, deep, rapid, large-scale proteomics that allow researchers to accurately survey and analyze the full diversity of proteins across individuals, over time.

 

GEN Edge: What is Seer’s approach to creating a product suite?

Farokhzad: Our solution is called the Proteograph Product Suite. It comprises our proprietary engineered nanoparticles, of which we have a growing library of particles with different physical and chemical properties. The Proteograph also includes an automation instrument that lets the user perform the assay in hands-off fashion—16 samples with the current configuration of the platform. Then the Proteograph Analysis Suites on the backend allows the scientists to go from biological content and data to biological insight. That solution sits upstream to an installed base of detectors (or detector) of choice. Today, this is a mass spectrometer, of which there are about 50,000 of them installed globally.

About 15,000 of them are installed for proteomic work, by folks who use mass spec today to access proteins in a biological sample. Seer’s solution takes the complexity away from what sits upstream and allows you to use that detector at a speed and scale that was previously not possible. We use the razor/razorblade business model, where you install the instrument, and the core business is the revenue that comes from the sale of consumables.

 

GEN Edge: What is Seer’s approach to partnerships?

Farokhzad: In life, you always have partners. There are aspects of Seer’s business that we make, engineer, and manufacture ourselves. The consumable part of it, we design, engineer, and manufacture, including the engineered nanoparticles that sample the proteome. There are other components to the kits, like buffers, that we secure externally. The fluid-handling instrument has the Seer branding and is designed to run the Seer assay. Our partner Hamilton makes that for us. The software suite is a software application. We use an interface that our team has designed to help the customer leverage the data types that come from the product suite.

We do have several commercial partnerships. We have a commercial partnership with three of the largest mass spec providers—Bruker, Thermo Fisher, and SCIEX. It allows us to provide an end-to-end solution for a customer who may not have access to a mass spec but has access to proteomic content. This makes it an easy and streamlined adoption for those types of customers.

If I look at the overall landscape, there are conventional proteomic customers that have existing mass specs. But in the last 15 years, what we’ve seen happen with broad-scale access to next-generation sequencers is the initiation of large-scale studies—studies that [involve] maybe tens or hundreds of thousands [of DNA or RNA reads] and at a scale that just doesn’t exist today in unbiased proteomics experiments. To give you context, the largest published plasma proteomics study was defined as anything over 600 proteins. To the best of our knowledge, the largest published proteomic panel before was a study published with 48 samples—contrast that to the millions that we see in the genomic space.

Folks that do proteomics fall into two buckets in how they approach access to the proteome. [Scientists in the first group] look at it in a targeted way, which means they’ll create a ligand like an antibody or aptamer. There’s no shortage of ligands. You can create panels of these ligands. When you interrogate with these ligands, you will always see those particular proteins and fluctuations. [In the second group], there’s a whole set of other folks that approach the proteome in an unbiased way. Those folks say, “I don’t know what’s important, so I need to look at everything.”

In the case of the proteome, this is particularly relevant because we’re all born with roughly 20,000 genes. Every cell in our body has the same 20,000 genes. But as you go from the genome toward the proteome, you go from 20,000 genes to roughly a couple of hundred thousand transcripts, and then you end up at a million-plus proteins and protein variants. Biology is complex. At every step, you get logarithmic increases in complexity— changes in RNA and splice variants, like post-translational modification.

Keep in mind that proteins typically don’t work in isolation. They come together to form complexes, and then those complexes come together to form machinery that works together to do something in the body. When you have different variants of the protein, you create different variations of the machinery. The proteome is so complex that the capability to approach it in a targeted way just doesn’t exist.

To give you a sense, the proteome may have a million or several million protein variants. But even the most extensive panel to do a targeted proteomic study is in the neighborhood of a few thousand. You’re leaving a vast amount of content behind if you’re doing just targeted studies. The folks that approach it in an untargeted or unbiased way haven’t been able to do it at scale. For the first time, Seer allows these folks to do unbiased proteomic [analysis] at the same speed and scale to unbiased genomics, which became possible roughly 15 years ago when next-generation sequencing became available in the marketplace.

 

GEN Edge: How is Seer approaching the international market?

Farokhzad: We’ve signed an exclusive distribution agreement with Enlight Medical, a leading distributor of innovative medical diagnostics therapeutics devices in China. The agreement accelerates the commercial availability of Seer’s Proteograph product suite to the rapidly expanding Chinese market. We always had plans to be in China because we see that as a massive business opportunity.

We were initially anticipating entering the Chinese market somewhere in the second half of 2022. Still, three things came about faster than we had expected, allowing us to get into China earlier. First, as we put this product in the hands of customers, we saw exceptional product performance, which made it clear that the product is ready for international customers across every metric: robustness, run success, data quality, etc. The protocol approximately has been performing exceptionally well at customer sites.

Second, looking at just the caliber of established commercial and academic institutions in China and their demand for accessing the Proteograph encouraged us to go there sooner. The third factor was existing relationships: Enlight Medical’s CEO is someone previously from Illumina, well known to Seer’s president and COO.

 

GEN Edge: What are the next steps that you’d like to take as a company?

Farokhzad: We are at the very beginning of this journey. If I were going to compare it to a couple of different areas, I would say it was just like genomics 15 years ago, or it’s just like the Internet when it was coming out. The magnitude of what becomes possible when you give people the tools and the capability to access the molecular information of life, at a scale that was not possible before, is enormous. We want to be the leader in terms of a company that does that. What possibilities are we creating? There are some obvious implications of that in therapeutics and diagnostics. What’s equally, maybe more exciting, is what becomes possible that we don’t even know today.

For example, could you have imagined what could have been possible with the Internet when the Internet was coming out? Could you even imagine what would have been possible with genomics at scale 15 years ago? I don’t think so. There has been a massive need to annotate this vast amount of genomic content in terms of its functional relevance. That means that Seer could become a company that is a dominant player in that space. The likes of it in genomics would be a company like Illumina. In the same way, we’re going to create new end markets.

About a year ago, we spun off a company called PrognomIQ, the first to do unbiased, multiomic early detection of diseases like cancer and neurodegenerative diseases like Alzheimer’s at scale. We’re at the very beginning of this journey and we are excited about all the possibilities our technology can open up.

 

GEN Edge: Does Seer intend to create a detection device?

Farokhzad: The beauty of what we do is that we are detector-agnostic. The Proteograph product suite solves a problem that isn’t unique to mass spec. It’s unique to any detector that wants to address proteomic content. For example, today, the detector of choice is a mass spec for unbiased proteomics. The Proteograph works with every one of them.

Several companies, some private and some public, are developing new detectors. Their aspiration is that they may replace the mass spec in the future. The Proteograph will sit upstream to their instrument. If we went down a path of a detector, we would narrow our market.

I would rather do the innovation on the Proteograph side of it and always be on the very edge of innovation. How do you sample the complexity of the proteome to go deeper and catalog all the protein variants? In the same way that today we have catalogued an astronomically large number of genomic variants. Still, with the million genomes and 10 million exomes that have been sequenced, we have now identified over 695 million genetic variances across studies at the population level. But we know almost nothing about what these mean in terms of their function. A subset of those variants are within exons that could impact proteins, and protein changes create different protein variants. Just like those genomic variants that have been identified; new protein variants will be identified.

We plan to keep our focus and attention squarely on innovation that happens upstream to the detector. However, we would never rule anything out in terms of what the future brings. Being true to our mission, we spun off a liquid biopsy company (PrognomIQ) to signal to the world that we are very focused on our business model and that we want to be a definitive leader in the tool space. But I will reserve my right to change my mind in the future if a business opportunity or market condition merits it for us to take a different route!