Structure Therapeutics saw its newly-public U.S. American Depositary Shares (ADSs) rise 70% on their first day of trading, after completing a $161 million initial public offering (IPO)—by far the largest IPO to date this year, and intended to fund development of its G-protein coupled receptor (GPCR)-based candidates for treating chronic metabolic and pulmonary diseases.

The upsized IPO is about $36 million above the $125 million estimate offered on January 30 by Renaissance Capital, which tracks the IPO market.

Structure finished its first day of trading at $25.57 per ADS—70% above its IPO price of $15, the high point of its price range. The company originally planned to sell 8.95 million shares last week, but boosted that to 10.74 million ADSs by the time it announced the pricing of its IPO on Thursday evening.

The closing price was 6% below Structure’s high price for the day of $27.18 per ADS, reached at 11:06 a.m. Structure’s ADS began trading six minutes earlier at $24.13.

Structure trades its shares on the Nasdaq Global Market under the symbol GPCR.

Gross proceeds for Prime could reach $185.265 million; Structure has granted the underwriters of its IPO a 30-day option to purchase up to an additional 1.611 million ADSs at the IPO price, less the underwriting discounts and commissions.

Structure previously projected it would generate between $111.5 million and $129.0 million in net proceeds, based on selling 8.95 million ADSs at $15 a share, the midpoint of its earlier pricing range of $13 to $15 per ADS.

At $14 a share, Structure said, the largest share of net proceeds—approximately $90 million—would fund continued development of its Glucagon-like peptide-1 receptor (GLP-1R) franchise, including the completion of a Phase Ib multiple-ascending dose (MAD) study and Phase IIa proof-of-concept study, as well as next-generation GLP-1R candidates that include dual GLP-1R/glucose-dependent insulinotropic polypeptide receptor (GIPR) agonists.

The company also projected using approximately $13 million in net proceeds to advance the development of its active human apelin receptor (APJR) agonist program and Lysophosphatidic acid receptor 1 (LPA1R) antagonist program. For the APJR program, Structure plans to launch a Phase I formulation bridging pharmacokinetic (PK) study as well as additional preclinical development studies in idiopathic pulmonary fibrosis (IPF) and pulmonary arterial hypertension (PAH). Advancement of the LPA1R program will include preclinical development and the start of a first-in-human study in IPF, Structure said.

The remainder of the net proceeds, the company added, would fund other research and development activities and general corporate purposes, “which we expect will include the hiring of additional personnel, capital expenditures, and the costs of operating as a public company.”

Year’s largest biotech IPO

Structure is far and away the year’s largest biotech IPO to date in 2023. Then again, only two other biotechs have joined Structure in going public so far this year: On January 19, Cadrenal Therapeutics raised $7 million gross by pricing 1.4 million shares at $5.00 a share. Cadrenal is developing tecarfarin, a late-stage novel therapy designed to prevent systemic thromboembolism in patients with end-stage renal disease and atrial fibrillation.

Six days later Genelux, which develops next-generation oncolytic viral immunotherapies for patients with aggressive and/or difficult-to-treat solid tumors, raised $15 million gross by pricing 2.5 million shares at $6 a share.

EY recorded just 17 IPOs being priced in the United States and Europe in 2022, down 89% from 158 a year earlier. The largest IPO of 2022 was Prime Medicine’s initial offering, which raised $180.3 million in net proceeds for the developer of a “search and replace” gene editing platform.

Structure disclosed its IPO plans on January 12. In its most recently available Registration Statement, filed January 30, Structure disclosed its pipeline of four small molecule therapeutics, two of which are in Phase I study:

  • GSBR-1290, an oral GLP-1R agonist indicated for type 2 diabetes and obesity.
  • ANPA-0073, an oral small molecule APJR agonist being developed for IPF and PAH.

The other two candidates include LTSE-2578, an oral LPA1R indicated for IPF; and GSBR Next Gen, a dual GLP-1R/GIPR agonist also indicated for type 2 diabetes and obesity.

“By leveraging our world-class GPCR know-how, we aim to design differentiated small molecule therapies to overcome the limitations of biologics and peptide therapies targeting this family of receptors,” Structure stated in its Registration Statement. “We believe the strengths of our platform position us to develop oral small molecule drugs that can deliver biologic-like activity and specificity. 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 added.

SAD, MAD studies

In September, Structure completed a Phase I single-ascending dose (SAD) study of GSBR-1290, reporting that the drug was generally well tolerated and demonstrated dose-dependent PK and pharmacodynamic (PD) activity. That same month, Structure received FDA allowance to launch a Phase Ib proof-of-concept study in type 2 diabetes and obesity.

Structure began a Phase Ib MAD study of GSBR-1290 in January, with plans to submit a protocol amendment to the FDA in the second half of 2023 to transition the trial into a Phase IIa proof-of-concept study in type 2 diabetes and obesity.

“We expect to report topline data for the Phase Ib study and Phase IIa study with the expected initiation in the second half of 2023,” Structure stated.

As for ANPA-0073, Structure completed a Phase I SAD and MAD study evaluating the drug, reporting it to be generally well tolerated in healthy human volunteers. “We expect to conduct additional preclinical studies to be followed by a Phase I formulation bridging PK study in Australia,” the company added.

LTSE-2578 was selected for development last month and is expected to begin a first-in-human study in 2024.

Structure is headquartered in South San Francisco, with R&D operations based in Shanghai. Structure—which changed its name from ShouTi last year to reflect its focus on structural biology and computational design—was co-founded by CEO Raymond Stevens, PhD, and Schrödinger, a company known for pioneering work in computational, physics-based drug design,

While at the Scripps Research Institute (now Scripps Research) in 2007, Stevens’ lab solved the first structure of a human GPCR, as well as many of the unique human GPCRs that have been structurally determined in the human proteome. He founded Syrrx, acquired by Takeda Pharmaceutical in 2005, and later established the Bridge Institute at the University of Southern California; the iHuman Institute at ShanghaiTech University; and the GPCR Consortium, a public-private global collaboration advancing GPCR research.

By August 2022, Structure had grown its private financing to $198 million, the final piece of that coming when the company completed an oversubscribed $33 million financing round that extended a $100 million Series B financing completed the previous year.

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