Diabetes and obesity can be managed with a slate of blockbuster products, many of them comprised of proteins and peptides—large molecules that must be administered as injections. Structure Therapeutics is developing drugs that go after the same target as those biologics, but in a pill formulation. The biotech already has some human data from its research. Now it has $161.1 million in IPO cash to ramp up clinical development.

Structure found enough investor interest to boost the deal size, which amounted to 10.7 million American depositary shares offered at $15 each—the top of the projected price range. Those shares began trading Friday. The focus of the company’s science is conveyed by its new Nasdaq stock symbol: “GPCR.”

G-protein-coupled receptors, or GPCRs, are found on cells throughout the body. These receptors play roles in a wide range of physiological and pathological processes. Many FDA-approved drugs already target GPCRs, but the easy targets have already been hit. Biotech startups have launched to find ways to target the GPCRs long considered undruggable. The GPCRs that Structure focuses on are already addressed by biological drugs and drug candidates, but the company aims to hit them instead with small molecules.

GPCR drug research poses several hurdles. While GPCRs are found throughout the body, these receptors are found in small numbers on cell surfaces, Structure said in the IPO filing. These receptors are also difficult to characterize structurally and they send signals through multiple pathways, which can limit activity and increase side effects—properties less than ideal for any drug. Structure’s technology platform uses computational techniques that its says enables the visualization of three-dimensional protein structures and their interactions with a small molecule.

“We believe the strengths of our platform position us to develop oral small molecule drugs that can deliver biologic-like activity and specificity,” the company said in the filing. “Oral small molecules can address many of the key limitations of biologic and peptide drugs, thereby significantly improving patient access. We believe this is particularly important for the most prevalent chronic diseases including those involving the metabolic, cardiovascular, and pulmonary systems.”

Structure’s lead drug candidate, GSBR-1290, is designed to bind to and activate glucagon-like peptide-1 receptors (GLP-1R). Found on the beta cells of the pancreas, these receptors play a role in insulin secretion and are validated targets for type 2 diabetes and obesity drugs. Eli Lilly’s Trulicity and Novo Nordisk’s Ozempic are among the blockbuster peptide drugs that activate GLP-1. Drugmakers aim to make these products as convenient as possible with self-injection devices. But manufacturing peptide drugs is still complex and expensive and these medicines require cold storage.

As a small molecule, Structure’s lead drug candidate is less expensive to make and easier for patients to take as a once-daily pill. A Phase 1 test of GSBR-1290 in healthy volunteers was completed last September, showing the drug was safe and well tolerated. A Phase 1b study began last month with a targeted enrollment of 24 participants between the ages of 18 and 55 who are overweight or obese. Structure plans to transition to a Phase 2a study in type 2 diabetes and obesity in the second half of this year. Preliminary data for both studies are expected in the second half of 2023, the company said in the IPO filing.

Novo Nordisk already has an oral GLP-1-targeting drug with Rybelsus. That drug uses the same peptide as Ozempic, but it’s made with an ingredient that facilitates stomach absorption, making pill formulation possible. But Structure notes in its filing that a limitation of Rybelsus is its strict dosing protocol. The drug  requires up to four ounces of water and no food or beverages within 30 minutes of dosing. Structure also says the ingredient Novo Nordisk uses to enhance absorption may affect absorption of other medications. That’s important because diabetes patients typically take multiple drugs to manage the chronic condition.

The chase for an oral GLP-1-targeting small molecule includes Pfizer, which has reached mid-stage clinical development with its candidate, danuglipron. Also in Phase 2 is Eli Lilly’s orforglipron, a GLP-1-targeting small molecule formerly known as LY3502970. Structure aims to take its small molecule approach further with a drug that hits both GLP-1 and GIPR. Those are the same two targets addressed by Lilly’s biologic drug Mounjaro, which the FDA approved last spring as a treatment for type 2 diabetes. Lilly has begun a rolling submission seeking to expand the drug’s approval to include weight loss.

Cardiopulmonary indications are another focus for Structure. ANPA-0073 is a small molecule designed to target the apelin receptor, a GPCR that plays a role in vasoconstriction and dilation, among other physiological activities. A Phase 1 test completed last September showed the drug candidate was well tolerated by healthy participants. Structure envisions that molecule as a potential treatment for idiopathic pulmonary fibrosis (IPF) and pulmonary arterial hypertension (PAH). Also for IPF, the company has an additional drug program targeting the lysophosphatidic acid 1 receptor. Structure aims to start a Phase 1 test of that molecule in 2024. The IPF and PAH focus sets up Structure for potential competition with numerous companies developing small molecules for those indications.

Structure is led by CEO Raymond Stevens, a former Scripps Research scientist whose lab solved the first structure of a human GPCR in 2007, according to the prospectus. Stevens has founded several structure-based drug discovery companies. In 2016, Stevens and computational drug design company Schrödinger co-founded Structure, which at that time was known as ShouTi Pharmaceuticals. In 2019, the startup reorganized as a Cayman Islands exempt company. Last summer, ShouTi changed its name to Structure Therapeutics. The company maintains an executive office in South San Francisco and has additional operations in Shanghai.

From its 2016 inception up to the IPO, Structure raised $198 million, according to the filing. In 2021, the company closed a $100 million Series B financing that was extended by $33 million last August. The biotech’s largest shareholder is Sequoia Capital China, which owns a 7.65% post-IPO stake, the filing shows. BVF Partners owns 7.1%; ERVC Healthcare owns 6.2%.

At the end of 2022, Structure said its cash position was about $90.8 million. That capital, combined with the IPO proceeds, will support the pipeline. Approximately $90 million will go toward lead drug candidate GSBR-1290, including the completion of Phase 1b and Phase 2a testing, according to the filing. The cash will also support the development of the dual GLP-1/GIP-targeting drug candidate. Structure has budgeted $14 million for early clinical development of its apelin receptor program in IPF and PAH, as well as the preclinical development and start of human testing for its lysophosphatidic acid 1 receptor-targeting molecule. The company estimates its cash will be enough to last through at least 2025.

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