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Startup Pepper Bio Touts 'Transomics' as Key Strategy in its Drug Discovery Efforts

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CHICAGO – While multiomics seems to be a top biotech buzzword these days, drug discovery and bioinformatics startup Pepper Bio is trying to make a name for itself in the field of transomics.

To that end, the Boston-based startup is leveraging support from Merck and other entities as part of an accelerator program to try and hone its strategy for applications such as phosphoproteomics analysis.

"I wouldn't consider [transomics] a new science. I would consider it the final piece of the puzzle that genomics started," said CEO and Cofounder Jon Hu.

According to Hu, genomics is more or less the "blueprint" of what can happen in biology. "But outside of genomics, there are a series of downstream effects that happens up until the biological activity stage," he explained. Transomics to him is the "integrated analysis of all of the different stages to give you a comprehensive view of biology."

The concept of transomics is not new, though the definition and usage varies. Huntsville, Alabama-based Transomic Technologies, which offers CRISPR gene editing, RNA interference, and gene expression products and services, has been around since 2012.

Since 2014, the US National Heart, Lung, and Blood Institute has a project called Trans-Omics for Precision Medicine, or TOPMed, which now includes more than 80 studies in the US and internationally.

A 2016 paper in Trends in Biotechnology defined transomics analysis as "a technology for reconstructing a global biochemical network by connecting multiomic layers."

An article published two years later in Cell Biology and Toxicology went further, discussing "clinical" transomics. The authors called this "a new emerging scientific discipline that integrates clinical phenomes with molecular multiomics, in order to further understand molecular mechanisms of disease pathogenesis and progression, patient sensitivity to therapy and prognosis, and therapy design and development."

Hu said that companies that focus on multiomics tend to look at genomics, proteomics, transcriptomics, and other omics layers independently, leading research groups to work in isolation. "They rarely talk to each other," he said. "Unfortunately, that's not really how biology works."

There can be discrepancies between independent analysis of DNA, RNA, and proteins, for example. "If you're looking for agreements between layers as your North Star, then you're going to end up with a lot of erroneous conclusions," Hu said.

"This emphasis on transomics is the future," Hu claimed. "This is really the only way that you can understand biology well enough to be reasonably confident in what you're developing."

One part of Pepper Bio's strategy is to include phosphoproteomics data.

Hu explained that biologists are good at "measuring what's there," such as an elevated level of a specific protein, but they often struggle with explaining the function of what is there, especially when a protein is turned off due to a mutation.

"We're going to capture that [phenomenon] directly," Hu said. "We look at these molecular switches to figure out what it is that the protein is actually doing."

Hu said that a lot of people have wanted to take advantage of transomics for years, but have not been able to work through the complexities. For example, it is difficult to capture data to determine whether a given site on a protein is phosphorylated, though hardware advances have improved this process.

"The challenge of that is, what do you do with that information? Knowing that sites … on these proteins are phosphorylated doesn't mean anything to me," Hu said. "I need to be able to figure out what that means. You need a dictionary to interpret," meaning a proper knowledgebase.

According to Hu, current innovation in phosphoproteomics is happening around the creation of knowledgebases.

Support from Merck, others

Last month, Pepper Bio became one of nine companies selected for the first cohort of the Merck Digital Sciences Studio (MDSS), a startup accelerator program run by Merck, Microsoft for Startups, and the New Jersey Institute of Technology's New Jersey Innovation Institute.

Participants receive unspecified direct investments from the Merck Global Health Innovation Fund, Northpond Ventures, and McKesson Ventures to develop digital technologies for drug discovery and development. They also have access to workshops, mentorship, entrepreneurial coaching, and credits for the Microsoft Azure Cloud, as well as office space in Newark, New Jersey, and Cambridge, Massachusetts.

Other omics-focused participants among the initial cohort include IndyGeneUS AI, Magna Labs, and Perceiv AI.

According to the Merck, the MDSS program, which started in December and will run through September, will "focus on important and disruptive bio technical approaches in artificial intelligence (AI) and machine learning (ML)."

Hu said that Pepper Bio applied for the program for the access to Merck scientists who can provide guidance on what technology the startup should build next.

While the MDSS program is only 10 months long, the goal is to create sustainable companies that Merck, Microsoft, the New Jersey Innovation Institute, and venture capital firms might want to back for the long term.

Pepper Bio, which was founded in 2020 and emerged from stealth in 2021, has an AI analysis platform that CSO and Cofounder Samantha Strasser began creating the technological foundation for when she was a Ph.D. student at the Massachusetts Institute of Technology nearly a decade ago.

The platform is entirely cloud-based, currently hosted on Amazon Web Services. However, because Microsoft is one of the partners in MDSS and is providing credits for its Azure cloud, Hu expects the startup to migrate to Azure eventually.

However, Hu wants Pepper Bio to be seen as more of a drug developer than contract research organization or bioinformatics firm. While it does work with pharma companies to help them make sense of biomedical data and identify targets and new compounds, the startup has its own research pipeline.

That pipeline includes two oncology programs, in MYC-addicted lymphatic and liver cancer, the result of a partnership with the laboratory of Dean Felsher, director of translational research and applied medicine at Stanford University.

Within MDSS, Pepper Bio is planning on launching a pilot project with Merck in the first half of the year, then using the rest of the program time to refine and validate its technology. "The goal, obviously, is to have these be successful programs so that they can then transition to being more full partnerships" with MDSS partners and investors.

Hu said that Pepper Bio has not settled on a direction to go with the pilot, but suggested it would involve one of two of the fledgling company's strengths.

"We're good at identifying novel targets for disease and on understanding the implications of targeting those targets," the Pepper Bio CEO said. "We're [also] good at understanding what happens when a drug enters a biological system."

To achieve the latter, Pepper Bio does not run narrow assays that lead to biased analyses. "We don't preselect," Hu said. "We look at the overarching global impact of a drug."

Hu said that a scientist at one major pharma company that Pepper Bio has had discussions with is not even interested in transcriptomic data because it is too far upstream to be useful in drug development.

Pepper Bio entered into a partnership with an undisclosed top 10 pharma firm late last year. In addition, Hu said that Strasser is leading work with an undisclosed partner in neurodegenerative diseases with an eye toward publication. He said that he is contractually prohibited from saying what area of neurodegenerative disease this partnership is covering.

Pepper Bio is also in the process of closing a seed financing round. Expect an announcement in the next couple of months, according to Hu. The firm had an unspecified pre-seed round in 2021, led by NFX, and raised an undisclosed amount of additional funding from Reinforced Ventures and VSC Ventures in early 2022.

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