Pfizer partners with tiny Cambridge startup to develop new COVID pills

Clear Creek Bio has also raised $30 million from investors.

Dr. Vikram Sheel Kumar, cofounder and chief executive of Clear Creek Bio, based in Central Square, Cambridge.Clear Creek Bio

The coronavirus hasn’t seen the last of Pfizer yet. The pharmaceutical giant has tapped Clear Creek Bio, a tiny Cambridge startup, for help in developing new antiviral pills that treat COVID-19, the companies said Tuesday.

Clear Creek will receive an upfront payment from Pfizer and potential milestone payments as part of a research collaboration to make new drugs that inhibit a protein that the coronavirus requires for replicating. Financial details were not disclosed.

This year Pfizer expects to make $22 billion from sales of its COVID pill Paxlovid and $34 billion from its COVID vaccine, Comirnaty. Sales of both products are expected to drop next year. In a statement, the company said it would advance its own programs and partnered ones to find additional therapies or combinations of therapies to treat coronavirus infections.

Charlotte Allerton, Pfizer’s chief scientific officer of anti-infectives and head of medicine design, said in a statement that COVID-19 has “the potential to remain a global health concern for years to come” and that it “is critical that we try to stay ahead of the virus.”

That decision is a boon to Clear Creek, which began working on ideas for the new drug in the spring of 2021. “We went from idea to deal in under 20 months,” cofounder and chief executive Dr. Vikram Sheel Kumar said in an interview.

Clear Creek, founded in 2017, has maintained a low profile until now. Kumar runs the company from a small office he rents above the H Mart grocery store in Central Square. The company’s approximately 10 full-time employees work remotely, and the startup relies on contract research organizations to conduct its lab experiments. “I definitely have the lowest rent for any biotech in Cambridge,” Kumar said.

The startup raised $30 million from Boston investment companies RA Capital and Cormorant Asset Management during the pandemic, Kumar said. Initially, Clear Creek tried repurposing an experimental cancer drug to treat COVID, but in April 2021, investors at RA Capital told the startup to begin working on ideas for new antivirals tailored to the coronavirus. It decided to take aim at a protein the virus needs to make more copies of itself.

During an infection, the coronavirus makes several proteins that are part of the molecular machines it uses to replicate. But those machines don’t emerge fully formed; some assembly is required. The proteins are initially tethered together, like pieces of a plastic model that need to be punched out of their mold. And the virus has two pairs of protein shears, called proteases, dedicated to neatly clipping free those parts.

Paxlovid inhibits one of those shears known as the main protease, or 3CL protease. Last month, the Japanese drugmaker Shionogi won emergency approval in Japan for its inhibitor of that protease. Other firms, including Watertown-based Enanta Pharmaceuticals, are also developing protease inhibitors that could be direct competitors to Paxlovid.

Clear Creek has taken aim at the second, lesser-studied coronavirus protease, known to scientists as papain-like protease, or PLpro. In addition to aiding viral replication by freeing different pieces from the protein mold, it also chops up human immune system proteins to remove innate defenses that would normally help suppress infection.

Kumar said that Clear Creek is in the advanced stages of optimizing its lead drug candidates, but he wouldn’t say if they’ve been tested in animal studies yet. Pfizer will be responsible for clinical trials once the two companies identify a drug candidate to test in humans. It’s too soon to say whether the drug would be used as an alternative to Paxlovid or in combination with it.

“If you look at where we are three years into the pandemic, we know that this virus is highly unpredictable, but we also know that to effectively treat viruses you often need multiple mechanisms of action,” Kumar said.

Clear Creek has a second antiviral program it started earlier in the pandemic with the experimental drug brequinar, which it acquired from Bristol Myers Squibb in 2017 with plans to develop it as a leukemia therapy.

Brequinar inhibits a human enzyme needed to make the building blocks of DNA and RNA, and some early-stage lab studies suggest that the drug could help stop haywire cancer cells from growing or even starve viruses of the materials they need to replicate.