Many proteins in the body are known to cause disease but remain stubbornly out of reach for the traditional ways of drugging a target. Parabilis Medicines has developed a new therapeutic modality to address such “undruggable” proteins. While this approach has potential applications in a wide range of diseases, Parabilis chose cancer as the proving ground for its technology. With a lead drug candidate on the path to a pivotal clinical trial, the company has joined the public markets, raising $745 million to finance its research.
Parabilis’s strategy is apparently resonating with investors. After setting preliminary IPO terms last week, the biotech found sufficient investor interest to boost the deal’s size twice in the same day. Early Tuesday, the biotech proposed offering 33.3 million shares in the range of $17 to $19 each. When Parabilis priced the IPO late Tuesday, it ended up offering 33.5 million shares for $20 each, raising $670 million. Concurrent with the IPO, Parabilis raised an additional $75 million from a private placement with Regeneron Pharmaceuticals, bringing the total haul to $745 million. Parabilis’s shares debuted on the Nasdaq Wednesday under the stock symbol “PBLS.”
Many of the known disease-driving proteins remain elusive because they are inside a cell. These proteins also have flat surfaces that make it difficult for a drug to bind. While small molecules can enter cells, they cannot bind flat surfaces, Parabilis said in its IPO filing. Antibodies can bind flat surfaces but cannot enter cells.
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Parabilis’s drugs are peptides with a literal twist. These peptides are engineered to take on an alpha helix structure, resembling a spiral in shape. This structure was inspired by nature’s frequent use of alpha helices to bind to flat protein surfaces to get across cellular membranes, Parabilis said in its IPO filing. The stabilized, alpha helix-shaped Parabilis drugs are called Helicons. Once inside a cell, a Helicon can take a number of approaches to addressing a disease-driving protein.
“Helicons combine the precision of antibodies and biologics with the intracellular access and tunability of small molecules in a single modality — enabling direct engagement of historically inaccessible protein targets,” Parabilis said in the IPO filing. “Our proprietary Helicon discovery platform allows us to integrate ligands and additional functionalities at multiple positions to precisely tune potency, selectivity, and pharmacologic properties.”
Lead program zolucatetide is a Helicon designed to inhibit a key part of Wnt/beta-catenin cell signaling, a pathway that regulates cell proliferation and differentiation. Hyperactivation of this pathway is a known driver of cancers. The first disease target that Parabilis has selected for zolucatetide is desmoid tumors, a rare type of tumor that develops in connective tissue.
The lone FDA-approved treatment for desmoid tumors is Ogsiveo, an oral small molecule now marketed by Merck KGaA. Ogsiveo inhibits a particular enzyme that activates a receptor whose dysregulation contributes to tumor growth. This drug’s clinical trials showed high rates of side effects, including severe diarrhea, rash, and ovarian dysfunction in 75% of female trial participants. Furthermore, many patients don’t respond to Ogsiveo and for those who do, it can take months.
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Parabilis sees an opportunity to bring desmoid tumor patients a better and more tolerable therapy. A Phase 1/2 study test of intravenously infused zolucatetide is ongoing. This study enrolled 38 participants; of the 25 that were evaluable as of late February, all showed tumor reductions, according to the filing. Of the 19 participants who had at least two scans after baseline, 74% (14 of 19) had on objective response (a 30% or greater tumor reduction from baseline). One patient showed a compete response. So far, zolucatetide has been safe and well tolerated with no treatment related adverse events leading to discontinuation of the study drug, according to the filing.
Parabilis said it expects zolucatetide’s Phase 3 test in desmoid tumors will begin in the first half of 2027. Additional early-stage studies are underway evaluating this drug in familial adenomatous polyposis (FAP), a rare disease characterized by precancerous polyps in the gastrointestinal tract. There are currently no FDA-approved therapies for FAP. Parabilis is also evaluating zolucatetide in additional rare tumors, liver cancer, and colorectal cancer. The biotech’s pipeline includes two preclinical Helicons in development for prostate cancer. In the filing, the company said it plans to evaluate Helicons in other therapeutic areas in the future.
Parabilis formed in 2015 based on research of Greg Verdine, a Harvard University chemistry professor who has become a serial biotech entrepreneur. The in-licensed technology became Parabilis’s Helicon discovery platform. Using artificial intelligence and machine learning techniques, this platform identifies proteins amenable to Parabilis’s approach and designs Helicons for those targets. Verdine was the company’s CEO until 2023, when Johnson & Johnson veteran Mathai Mammen took over the top role. The biotech was known as FogPharma until changing its name to Parabilis Medicines in 2024.
From its 2015 formation up to the IPO, Parabilis said it had raised about $811.8 million in equity financing. The most recent financing was a $305 million Series F round in January. According to the filing, Parabilis’s largest shareholder is Fidelity Management & Research company with a 7.3% post-IPO stake, followed by RA Capital Management’s 6.5% stake.
In May, Parabilis and Regeneron began a partnership focused on using the Helicon technology to develop a new class of drugs called Antibody Helicon Conjugates (AHCs). Specific indications remain undisclosed, but the companies said the alliance would focus on undruggable targets. Regeneron paid Parabilis $50 million up front and agreed to invest $75 million in the biotech’s next equity financing, which turned out to be the private placement concurrent with the IPO.
As of the end of the first quarter of this year, Parabilis reported its cash position was $329 million. The company plans to spend $150 million on zolucatetide in desmoid tumors, a sum the company expects will support clinical development all the way through the readout of topline Phase 3 data. Another $120 million will support clinical development of zolucatetide in other indications. The company has also budgeted $190 million for other programs in its pipeline that it plans to advance through Phase 1 testing. Parabilis said its capital plus Regeneron’s upfront payment is expected to support operations into the second half of 2029.
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