By Jonathan D. Grinstein, PhD
My interview with Pepper Bio CEO Jon Hu begins with one of the most frequently repeated phrases I hear when speaking with drug developers: “We are a drug developer trying to tackle untreatable diseases,” Hu says.
In Hu’s opinion, however, Pepper Bio’s computational approach that uses “functional” omics data, which they’ve dubbed “transomics,” will set them apart in their quest to combat incurable diseases.
So I asked Hu, “What distinguishes ‘transomics’ from ‘multiomics’?”
Hu’s response is a two-parter.
First, even though everyone uses multiomics, the major pharmaceutical companies have departments tasked with gathering and analyzing data for a single omics layer, and it is precisely in this isolation that multiomics problems arise.
“If all you’re doing is looking for agreement between omic layers, you’re reliable to miss out on a lot of real biology that happens because there are lots of things that could happen in between layers that start to change the directionality,” said Hu. “We integrate across the entire omics data set first, then perform our analysis on that integrated data set.”
Second, Hu thinks that no one using multiomics is studying biological function.
“While everyone is interested in biological function, the vast majority of the time, they answer a slightly different question when they perform these biological experiments, which is to answer, ‘what’s there?’ ” said Hu. “People measure expression levels and make a super general assumption, which is that the more of something that is there, the more of something’s activity that occurs. Unfortunately, that doesn’t always hold.”
To address these two issues, Pepper Bio’s COMPASS platform integrates machine learning across four key omic layers—genomics, transcriptomics, proteomics, and phosphoproteomics. It is the last omic on that list that led to the term “transomics,” as it deals with post-translational modifications.
“If you scout out the entire land of post-translational modifications, phosphorylation is the one that occurs the most frequently and is also the one that we know the most about so far,” said Hu. “We can map a certain phosphorylation event to an outcome that we care about because the raw data we get back is the phosphorylation of sites on proteins. But that’s useless unless we can interpret that and say, ‘These are the implications for which biological pathways are being activated, and then these are the implications for what sort of phenotypic response we expect to see from a patient.’ ”
Three years ago, Hu, who has a background in business, teamed up with Samantha Dale Strasser, PhD, to co-find Pepper Bio. With experience studying post-translational modifications, Strasser, who is also the company’s CSO, is driving the development of Pepper Bio’s solution to drive their drug pipeline is a computational platform, COMPASS. She’s been able to build it out enough that Pepper Bio has already led to partnerships with two major pharmaceutical companies.
Behind this initial concept and progress, Pepper Bio announced an oversubscribed $6.5 million seed round with participation from NFX, Merck Digital Sciences Studio, Mana Ventures, Silverton Partners, Tensility Ventures, VSC Ventures, and others. This funding will accelerate Pepper Bio’s transomics platform capabilities, fueling the pipeline.
Pepper Bio uses a two-pronged strategy: first, it develops drugs internally through an internal pipeline, and then partners with other companies to co-develop drugs.
Hu explained that Pepper Bio decided to concentrate on cancer for their internal drug pipeline because the disease’s clinical trials are well-established and therefore easier to pursue. In certain instances, Pepper Bio licenses assets that match the profile COMPASS has identified to develop its pipeline. Hu, however, added that for some of these, they are also developing molecules de novo as part of very early-stage programs. The lead candidate from Pepper Bio is anticipated to start clinical trials in late 2024.
Pepper Bio’s external partnerships are centered around neurodegenerative and inflammatory diseases.
“We help them answer one of two questions,” said Hu. “One is, ‘We have a drug and we’re not quite sure what this drug does, so please help us figure out what this drug does.’ The other question is, ‘We’re interested in a new disease; help us figure out what targets to go after for this particular disease.’”
According to Hu, the long-term objective is for Pepper Bio to eventually grow into those two additional disease areas as they develop their internal pipeline.
One thing that stood out from speaking with Hu is that Pepper Bio only consists of seven people. Not seventy. Not seven hundred. Just seven. These seven people run both arms of Pepper Bio.
“You don’t need a gigantic army of people to do things now that you would’ve historically needed because there is that ability to outsource to CROs and CMOs,” said Hu
The last piece of the puzzle
Hu traces the history of oncology to paint a picture of how Pepper Bio hopes to advance drug discovery. A century ago, cancer was primarily determined by its location in the body—breast or lung cancer—and chemotherapeutic treatments developed had high toxicity, low response rates, efficacy, and minimal added survival.
Twenty years ago, the field of oncology became more sophisticated, largely thanks to the genomics revolution. Cancers were no longer defined solely by their location but also by their mutation, as in HER2-positive breast cancer and EGFR-positive lung cancer. The improved understanding of cancer biology resulted in a new wave of drugs with lower toxicity and higher response rates, efficacy, and survival.
“What we see is a future filled with a transomic signature, and you would use that to identify what cancer you have, as an example,” said Hu. “By doing that, we can significantly boost response rates because we know which drugs will work on which types of patients. We will hopefully also increase efficacy while limiting toxicity as well.”
Hu predicts transomics will become the standard in 20 years, expressing confidence in this development.
Suppose Pepper Bio hopes to survive long enough to have a shot at spearheading the next wave of drug development. In that case, it needs to get a drug into clinical trials and see it through approval, commercial success, and the transformation of patients’ lives.