The steady rise of Prelude Therapeutics

By Dan Linehan
Special to Delaware Business Times

It’s natural to draw parallels between Kris Vaddi’s time discovering drugs at Incyte, where he spent 14 years, and his latest startup venture, Prelude Therapeutics. But there are many differences.

At Incyte, Vaddi joined a thriving public company with hundreds of millions in cash and investments when it moved to Delaware in 2001. Incyte’s resources made it possible to assemble a team of about 50 people, largely ex-DuPont employees, and target a broad scope of diseases.

Vaddi founded Prelude in 2016 with $5 million in startup funds, which necessitated a smaller team and narrower scope. The firm focused on just a handful of targets in an effort to find promising cancer drugs.
“We had a very limited internal infrastructure and had to rely heavily on external resources and academic networks,” Vaddi said.

Even if Vaddi didn’t build Incyte — and its billion dollar-a-year drug, Jakafi — from scratch, he learned how to shepherd a drug from promising idea to finished product. Drug discovery is often as much about perseverance as technological breakthroughs.

“A lot of startups don’t know how to take that long, hard road,” Vaddi said.

Whereas a tech company can sometimes develop a product in a few months, if not weeks, making a drug takes years of work even after promising results emerge from the lab. The drug needs to be tested in animals before limited trials in humans show it’s safe. After that, large-scale studies must show the drug is effective before it can be sold. The whole process takes an average of 12 years and hundreds of millions of dollars.

Since its initial $5 million seed funding, Prelude has attracted $30 million in a round of investment that ended in August. These investments tend to reflect investors’ confidence in the people behind a company as much as the value of its ideas, said Bill Provine, CEO of the Delaware Innovation Space, where the company moved in late 2017.

Vaddi isn’t the only experienced hand behind Prelude. Its leadership team, which came together based on shared history or professional networks, includes:

• Peggy Scherle, chief scientific officer, 16-year veteran of Incyte in drug discovery.

• Juan Luengo, vice president of drug discovery research, spent 27 years at a major pharmaceutical company, partly as a medicinal chemist.

• Aimee Crombie, vice president of research and development operations, formerly vice president of research
at a small company based in King of Prussia.

The fact that the team all lived in the Delaware region made the state a natural, but not preordained, fit for Prelude.

At home in Delaware

Though Delaware is not a conventional home for biotechnology startups — the Boston or San Francisco Bay areas are more popular — it had other advantages for Prelude.

While it might be easier to recruit and partner with other labs in denser biotech clusters, Vaddi said this region’s history of successful pharmaceutical companies has left it with vast resources.

At the same time, Prelude does not need to build a large team while it is still in the drug discovery phase. It has 23 employees now and must have at least 32 employees by 2020 to satisfy a condition of a $474,000 grant from Delaware’s Council on Development Finance. That hiring will come naturally as the company’s drugs enter research-heavy phases and require new expertise to perform them, said Scherle.

In the meantime, Prelude is searching for potential cancer drugs that can stop tumor growth at the cellular level.

A full pipeline

Though Prelude will be focusing on a few drugs, they will not be pinning all their hopes on a single prospect. Even a drug that passes initial human trials has on average a 10 percent chance of being approved as a marketable drug.

To hedge its bet, Prelude is developing multiple drugs at a time. By staggering drug development, it avoids bottlenecks at any individual phase and avoids placing its fate in the hands of a few drugs that might not work.
“We really are well suited to developing the pipeline; that’s our passion,” Vaddi said.

Prelude is now looking for promising drug candidates that target specific mechanisms tumors use to survive and grow. These medicines are first tested in the lab to test for beneficial properties, such as reaching the bloodstream after being taken by mouth or killing certain tumor cells while sparing normal cells, Scherle said.

Prelude’s goal is to put at least one of its compounds into human clinical trials in 2019.

The company is focusing on cancer drugs in three main areas: blood cancer, brain cancer and lymphomas, which begin in the immune system. But plans change. A potential drug that begins as a treatment for one cancer may actually be more effective on another. That was the case for Incyte’s blockbuster drug, Jakafi, which was initially targeted at a blood cancer called multiple myeloma.

“Then, one fine morning these [scientific] papers showed up,” Vaddi said, and the focus of the drug changed, to a bone marrow cancer called myelofibrosis. Later research trials allowed its use to be expanded to other conditions, a common path for new drugs.

A pharmaceutical company the size of Prelude typically builds on existing discoveries about how cancers grow — perhaps by finding new cancers to target or finding sub-groups of potential patients who may benefit due to their tumor’s specific genetic makeup — and leaves research on entirely new methods to larger, government-funded laboratories.

Even with this limitation, Prelude has the goal of developing drugs to help cancer patients for whom other options haven’t worked.

Much of the progress against breast cancer, to take an unrelated example, has been about finding patients whose specific cancers might be vulnerable to existing technology. Think of it like finding a target for a technology, rather than developing technology to hit a target.

“Our goal is connecting the dots where the dots already exist,” Vaddi said.

He chose the name for the company because he hopes it will be an introduction to a future in which cancer, if not cured entirely, is able to be controlled.

“I would like to be part of turning cancer into a more manageable disease to give lasting hope to patients,” he said.

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