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Topline GSBR-1290 Phase 2a 12-week obesity data, as well as data from formulation bridging and titration optimization study, on track for latter half of the second quarter 2024 Phase 2b study in obesity expected to begin as planned in the fourth quarter 2024 Year-end cash balance of $467.3 million expected to fund operations and key clinical milestones through 2026 SAN FRANCISCO, March 08, 2024 (GLOBE NEWSWIRE) -- Structure Therapeutics Inc. (NASDAQ: GPCR), a clinical-stage global biopharmaceutical company developing novel oral small molecule therapeutics for metabolic and cardiopulmonary diseases, today reported financial results for the fourth quarter and full year ended December 31, 2023, and highlighted recent corporate achievements. “In 2023 we demonstrated clear proof-of-concept with our lead GLP-1 receptor agonist, GSBR-1290, for obesity and type 2 diabetes. As a differentiated oral small molecule we have the scalability and manufacturing advantages to potentially meet the significant unmet need currently observed in the GLP-1 space,” said Raymond Stevens, Ph.D., Founder and CEO of Structure Therapeutics. “With a year-end cash balance of $467.3 million providing runway through the end of 2026, we are well-positioned to initiate and complete our Phase 2b trials for GSBR-1290 and accelerate development of our oral small molecule programs targeting amylin, GIP, and apelin receptors.” Recent Highlights and Upcoming Milestones GSBR-1290 for Type 2 Diabetes Mellitus (T2DM) and Obesity In December 2023, the Company reported clinically meaningful data from the Phase 2a study in T2DM demonstrating significant reductions in hemoglobin A1c (HbA1c) and weight at 12 weeks. Interim Phase 2a data from the obesity cohort demonstrated significant reduction in weight at 8 weeks. Across both cohorts, GSBR-1290 was generally well-tolerated with no treatment-related serious adverse events over 12 weeks and low study discontinuation rates due to adverse events related to study drug (2.8% in T2DM and 0% in obesity).Topline data from the obesity cohort of the Phase 2a study, including full 12-week efficacy data for 40 participants and safety and tolerability for all 64 participants. This study is fully enrolled and data are expected in the latter half of the second quarter of 2024.In preparation for later stage clinical trials, a formulation bridging and titration optimization study to evaluate capsule versus tablet pharmacokinetics (PK) and explore different titration regimens of GSBR-1290 is ongoing. This study is fully enrolled and data are expected in the latter half of the second quarter of 2024.The Company plans to initiate a global Phase 2b obesity study of GSBR-1290 in the fourth quarter of 2024.The Company plans to initiate a Phase 2 study in T2DM in the second half of 2024. GLP-1R Combination Programs: Amylin, GIPR, Apelin (APJR) Oral Small Molecule Amylin Program: The Company is developing amylin agonists for use either alone or in combination with GLP-1R agonists to treat obesity and associated diseases, and expects to select a development candidate in the second half of 2024.Oral Small Molecule GIPR Program: The Company is developing a GIPR selective agonist and GLP‑1R/GIPR combinations to treat obesity and associated diseases, and expects to select a development candidate in the first half of 2025.Oral Small Molecule Apelin Receptor (APJR) Program: The Company is evaluating its Phase 2 ready ANPA-0073, a biased agonist targeting APJR used in combination with weight loss medicines, for selective or muscle-sparing weight loss. ANPA-0073 is also being evaluated for idiopathic pulmonary fibrosis (IPF). The Company has completed a Phase 1 single-ascending and multiple-ascending dose study, in which ANPA-0073 was generally well-tolerated with no serious adverse event reported. LPA1R Program for Idiopathic Pulmonary Fibrosis (IPF) The Company is developing LTSE-2578, an oral small molecule antagonist that targets lysophosphatidic acid 1 receptor (LPA1R). Preclinical studies have demonstrated substantial anti-fibrotic activity in mouse models of fibrotic lung disease, and the Company expects to initiate a first-in-human study of LTSE-2578 in the second quarter of 2024. Corporate In 2023, the Company raised approximately $485.0 million of equity capital: $185.0 million in gross proceeds from the initial public offering in February, and $300.0 million in gross proceeds from the private placement equity financing in October. Fourth Quarter and Full Year 2023 Financial Highlights Cash Position: Cash, cash equivalents and short-term investments totaled $467.3 million at December 31, 2023. The Company expects its current cash, cash equivalents and short-term investments to fund operations and expected key clinical milestones through at least 2026. R&D Expenses: Research and development (R&D) expenses for the fourth quarter of 2023 were $20.0 million, as compared to $8.4 million for the same period in 2022. For the year ended December 31, 2023, R&D expenses were $70.1 million, as compared to $36.2 million for the full year 2022. The increase was primarily due to the advancement of the Company’s GLP-1R franchise and other research programs, clinical study activities and increases related to employee expenses, primarily due to an increase in personnel. G&A Expenses: General and administrative (G&A) expenses for the fourth quarter of 2023 were $11.0 million, as compared to $4.6 million for the same period in 2022. For the year ended December 31, 2023, G&A expenses were $32.7 million, as compared to $16.4 million for the full year 2022. The increase was primarily due to increases in professional services and employee related expenses as the Company expanded its infrastructure to drive and support the growth in its operations as a publicly-traded company. Net Loss: Net loss for the fourth quarter of 2023 totaled $24.5, with non-cash stock-based compensation expense of $2.1 million, compared to $11.9 million for the fourth quarter of 2022 with non-cash stock-based compensation expense of $0.6 million. For the year ended December 31, 2023, net loss totaled $89.6 million, with non-cash stock-based compensation expense of $8.2 million, compared to $51.3 million for the full year 2022 with non-cash stock-based compensation expense of $2.5 million. About Structure TherapeuticsStructure Therapeutics is a leading clinical-stage biopharmaceutical company focused on discovering and developing innovative oral treatments for chronic metabolic and cardiopulmonary conditions with significant unmet medical needs. Utilizing its next generation structure-based drug discovery platform, the Company has established a scientifically-driven, GPCR-targeted pipeline, featuring two wholly-owned proprietary clinical-stage small molecule compounds designed to surpass the limitations of traditional biologic and peptide therapies and be accessible to more patients around the world. For additional information, please visit www.structuretx.com. Forward Looking Statements This press release contains “forward-looking statements” within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. All statements other than statements of historical fact are statements that could be deemed forward-looking statements, including, without limitation, statements concerning the Company’s future plans and prospects, the Company’s anticipated cash runway, the clinical update from Structure’s Phase 2a study of GSBR-1290 in patients with T2DM and obesity, any expectations regarding the safety, efficacy or tolerability of GSBR-1290 and other candidates under development, the ability of GSBR-1290 to treat T2DM, obesity or related indications, the planned initiation and study design of Structure’s Phase 2b studies for GSBR-1290 in patients with T2DM and obesity and the timing thereof, and first-in-human study of LTSE-2578 and the timing thereof, respectively, the selection of a development candidate for the Company’s amylin receptor agonist program and GLP-1R/GIPR program, the planned timing of the Company’s data results and continued development of GSBR-1290, amylin and next generation GLP-1R/GIPR combination candidates and expectations regarding an oral development candidate targeting GLP-1R. In addition, when or if used in this press release, the words “may,” “could,” “should,” “anticipate,” “believe,” “estimate,” “expect,” “intend,” “plan,” “predict” and similar expressions and their variants, as they relate to the Company may identify forward-looking statements. Forward-looking statements are neither historical facts nor assurances of future performance. Although the Company believes the expectations reflected in such forward-looking statements are reasonable, the Company can give no assurance that such expectations will prove to be correct. Readers are cautioned that actual results, levels of activity, safety, performance or events and circumstances could differ materially from those expressed or implied in the Company’s forward-looking statements due to a variety of risks and uncertainties, which include, without limitation, risks and uncertainties related to the preliminary nature of the results due to length of the study and sample size, the risks that unblinded data is not consistent with blinded data, the Company’s ability to advance GSBR-1290, LTSE-2578, ANPA-0073 and its other therapeutic candidates, obtain regulatory approval of and ultimately commercialize the Company’s therapeutic candidates, the timing and results of preclinical and clinical trials, the impact of any data collection omissions at any of our clinical sites, the Company’s ability to fund development activities and achieve development goals, the impact of any global pandemics, inflation, supply chain issues, rising interest rates and future bank failures on the Company’s business, its ability to protect its intellectual property and other risks and uncertainties described in the Company’s filings with the Securities and Exchange Commission (SEC), including the Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2023, as filed with the SEC on November 17, 2023, and future reports the Company may file with the SEC from time to time. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management’s assumptions and estimates as of such date. The Company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law. STRUCTURE THERAPEUTICS INC.Condensed Consolidated Statements of Operations(unaudited)(In thousands, except per share amounts) THREE MONTHS ENDED YEAR ENDED DECEMBER 31, DECEMBER 31, 2023 2022 2023 2022Operating expenses: Research and development $20,042 $8,360 $70,103 $36,193 General and administrative 10,952 4,596 32,672 16,368 Total operating expenses 30,994 12,956 102,775 52,561 Loss from operations (30,994) (12,956) (102,775) (52,561)Interest and other income (expense), net 6,179 901 13,391 1,257 Loss before provision for income taxes (24,815) (12,055) (89,384) (51,304)Provision for income taxes (312) (180) 236 17 Net loss $(24,503) $(11,875) $(89,620) $(51,321) STRUCTURE THERAPEUTICS INC.Condensed Consolidated Balance Sheet Data(unaudited)(In thousands) DECEMBER 31, 2023 2022Assets Current assets: Cash, cash equivalents and short-term investments $467,323 $90,841 Prepaid expenses and other current assets 6,285 2,248 Total current assets 473,608 93,089 Property and equipment, net 3,228 1,031 Operating right-of-use assets 5,136 262 Other non-current assets 45 3,463 Total assets $482,017 $97,845 Liabilities, redeemable convertible preferred shares and shareholders’ equity (deficit) Current liabilities: Accounts payable $4,742 $6,009 Accrued expenses and other current liabilities 18,558 6,741 Operating lease liabilities, current portion 1,440 260 Total current liabilities 24,740 13,010 Operating lease liabilities, net of current portion 4,013 — Other non-current liabilities 298 — Total liabilities 29,051 13,010 Redeemable convertible preferred shares issuable in series — 199,975 Total shareholders’ equity (deficit) 452,966 (115,140)Total liabilities, redeemable convertible preferred shares and shareholders’ equity (deficit) $482,017 $97,845 Investors:Danielle KeatleyStructure Therapeutics Inc.ir@structuretx.com Media:Dan Budwick1ABDan@1abmedia.com

One concern about the GLP-1 class of metabolic disorder drugs is that the weight patients lose includes muscle as well as fat. BioAge Labs wants to test whether its experimental medication, dosed alongside Eli Lilly’s weight management drug Zepbound, can preserve muscle mass. The startup recently closed $170 million to finance a mid-stage clinical trial. BioAge develops drugs that address aspects of human aging. Its lead drug candidate, azelaprag, is a small molecule designed to bind to and activate the apelin receptor, which regulates muscle metabolism, growth, and repair. This drug came from the labs of Amgen, which initially developed it for treating heart failure. Amgen’s Phase 1 tests showed the drug hit its target with a clean safety profile, BioAge CEO Kristen Fortney told MedCity News in a 2022 interview. But as a heart drug, the results were “not dramatic,” she said. Amgen elected to shelve the molecule. Richmond, California-based BioAge licensed it from the pharma giant in 2021, with the goal of testing it as a way of preserving muscle mass in elderly people. In BioAge’s Phase 1b study enrolling 21 participants age 65 and older, results showed the experimental drug led to statistically significant prevention of muscle atrophy relative to a placebo after 10 days of bed rest. The company planned to proceed to larger Phase 2 test enrolling intensive care unit patients, who can lose more than 15% of their muscle mass in just one week, according to published research. Last fall, BioAge announced the Phase 2 trial would go in a different direction. Instead of testing azelaprag in ICU patients, the trial will evaluate the drug alongside Eli Lilly’s Zepbound. The injectable drug, which activates the GLP-1 and GIP receptors, is an incretin mimetic, a type of drug that works by mimicking hormones found in the gut. The new clinical trial plan is based on preclinical research in obese mice. Results reported last year showed that treating the mice with both azelaprag and Lilly’s drug led to greater weight loss than what was achieved with the Lilly drug alone. The drug pairing also led to improvement in body composition and muscle function. Under a collaboration agreement, Lilly will supply Zepbound for BioAge’s trial, which will be run in collaboration with Chorus, a small independent clinical development organization within the pharma giant. BioAge adjusted its focus for azelaprag after the company’s technology uncovered new insight about the molecule. The BioAge discovery platform, built on analysis of human longevity data, identified a link between the apelin pathway activity and physical function during aging, Fortney said in an email. While the Phase 1b clinical trial led to results showing significant muscle and metabolic benefits in healthy elderly volunteers on bed rest, the molecule’s mechanism has multiple potential applications, Fortney said. “Obesity is the indication we are focusing on given the strong weight loss synergy we see preclinically with incretins,” she said. “This is an oral drug with the potential to increase weight loss quantity with a fully oral regimen, as well as to improve weight loss quality.” Fortney said BioAge will share more details on the design of the Phase 2 trial in the future, but the study will compare azelaprag (known at BioAge as BGE-105) in combination with Zepbound versus Zepbound alone. The primary endpoint will be weight loss. In addition, the company will monitor exploratory endpoints related to improvement of body composition—the balance of lean mass to fat mass. BioAge’s new capital will finance the planned Phase 2 test, which is on track to start in mid-2024. The Series D round was led by Sofinnova Investments. New investors joining the financing include Longitude Capital, RA Capital Management, Cormorant Asset Management, RTW Investments, SV Health Investors, OrbiMed Advisors, Sands Capital, Pivotal bioVenture Partners, Osage University Partners, Lilly Ventures, and Amgen Ventures. The latest round also included participation from earlier investor Andreessen Horowitz. Here’s a look at other recent life science industry financing activity: —Frontier Medicines, developer of targeted medicines for oncology and immunology, closed $80 million in financing to support its pipeline. The biotech’s most advanced program is FMC-376, which is in development for treating patients whose cancer is positive for KRAS G12C. This mutation was first drugged by Lumakras from Amgen and then Krazati from Mirati Therapeutics. Both drugs lock KRAS G12C protein in an inactive state. Frontier’s drug candidate is designed to block this cancer-driving protein in either its active or inactive states, potentially offering an option for patients who have not responded to the Amgen or Mirati drugs. In addition to supporting FMC-376, which recently dosed the first patient in a Phase 1/2 study, Frontier said the new capital will support other wholly owned programs in its pipeline. Deerfield Management Company and Droia Venture co-led the company’s Series C financing, which also included “significant participation” by Belgium-based drugmaker Galapagos. Frontier last raised money in 2021, an $88.5 million Series B round. —Firefly Bio revealed $94 million to finance R&D of degrader antibody conjugates, or DACs, which carry a protein degrader as the drug payload. In preclinical research, the biotech said its drugs led to “significant reduction of tumor volume at very low doses.” Firefly was incubated by Versant Ventures, which co-led the startup’s Series A financing with MPM BioImpact. —Roche, already an investor in liquid biopsy company Freenome, led an additional $254 million financing for the company. South San Francisco-based Freenome will apply the cash toward ongoing pivotal clinical trials evaluating its blood screening technology in colorectal cancer and lung cancer. The company is also conducting a study of its technology as a way to detect multiple cancers. Roche last invested in Freenome two years ago, a $290 million infusion that followed the company’s $300 million Series D financing. —Latigo Biotherapeutics launched with $135 million to finance clinical development of a non-opioid drug that blocks NaV1.8, a sodium channel associated with pain. It’s the same target addressed by a Vertex Pharmaceuticals drug candidate that recently posted data showing it met its main Phase 3 goal assessing pain relief compared to a placebo. But on a secondary goal of showing superiority to standard of care Vicodin, the Vertex drug came up short. Thousand Oaks, California-based Latigo claims its drug could be best in the class of NaV1.8 inhibitors with rapid onset, meaningful efficacy, and superior safety. It’s currently in Phase 1 testing. Latigo’s Series A financing was led by Westlake Village BioPartners, which incubated the startup. —Cancer immunotherapy developer NextPoint Therapeutics added $42.5 million to its Series B financing, bringing the round’s total to $122.5 million. The drugs of Cambridge, Massachusetts-based NextPoint target the HHLA2 pathway. NextPoint first announced its Series B round last year. —Sudo Biosciences expanded its Series B financing by $31 million, bringing the round’s total to $147 million. The new investors are Dementia Discovery Fund, Leaps by Bayer, and UPMC Enterprises. Carmel, Indiana-based Sudo emerged from stealth in 2022 to develop small molecule drugs that address TYK2, an autoimmune disease target first hit by the Bristol Myers Squibb drug Sotyktu. —Alys Pharmaceuticals launched with $100 million from Medicxi, the investment firm that formed the company. The preclinical biotech, which focuses on developing treatments for immune disorders of the skin, was formed by combining six Medicxi portfolio companies. Target indications include atopic dermatitis, vitiligo, psoriasis, and mastocytosis. —Antibody drug conjugate developer ProfoundBio closed $112 million in financing, which will be applied to clinical development of its pipeline. Lead program rinatbart sesuctecan, or Rina-S, targets folate receptor alpha, a validated cancer target. A pivotal Phase 1/2 study is underway in ovarian cancer. Ally Bridge Group led the Seattle-based biotech’s Series B round. ProfoundBio, whose management team brings experience from ADC specialist Seagen, emerged in 2021 backed by a $55 million Series A financing. —Areteia Therapeutics expanded its Series A round by $75 million with the addition of new investors Viking Global Investors and Marshall Wace. The Chapel Hill, North Carolina-based biotech’s Series A financing was announced at $350 million in 2022. Lead drug candidate dexpramipexole comes from the labs of Knopp Biosciences. Areteia is currently testing the molecule in three Phase 3 clinical trials enrolling patients with eosinophilic asthma, a severe form of asthma. —Basking Biosciences raised $55 million in a financing led by Arch Venture Partners. Columbus, Ohio-based Basking will use the capital to continue clinical development of BB-031, a potential treatment for acute ischemic stroke. The Basking drug is a reversible RNA aptamer designed to target von Willebrand factor, a clotting protein. BB-031 is engineered for both rapid onset and short duration of effect. Basking plans to start Phase 2 testing later this year. —Neurona Therapeutics, developer of regenerative medicines for neurological disorders, closed $120 million in financing. The San Francisco-based biotech makes cell therapies from human pluripotent stem cells, which have the ability to become almost any type of cell. Neurona will apply the capital toward ongoing Phase 1/2 testing of NRTX-1001, developed as a one-time treatment to silence epileptic seizures. Viking Global Investors and Cormorant Asset Management co-led Neurona’s Series E round. —Cour Pharmaceuticals has already out-licensed a celiac disease therapeutic candidate to Takeda Pharmaceuticals, which has advanced the nanoparticle-based therapy to Phase 2 testing. Chicago-based Cour wants to develop its own drug candidates and it raised $105 million to support programs in type 1 diabetes and myasthenia gravis. Lumira Ventures and Alpha Wave Ventures co-led the Series A financing, which included participation from three big pharma companies. —Eyconis, a new company formed with assets from Ascendis Pharma, launched with a $150 million financing commitment from an investor syndicate that includes Frazier Life Sciences, RA Capital Management, venBio, and HealthQuest Capital. Eyconis, which will operate from Redwood City, California, has ophthalmology assets developed from Ascendis’s Transcon platform. Ascendis, which has an equity stake in Eyconis, granted the biotech rights to develop and commercialize Transcon ophthalmology products globally. —Synnovation Therapeutics, founded and led by veterans of Incyte, launched with $102 million for small molecule drugs addressing validated cancer targets. Lead program SNV1521 is a PARP1 inhibitor that is highly selective to that target and also has the ability to penetrate into the central nervous system. The Wilmington, Delaware-based company is testing this molecule in a Phase 1 clinical trial. Third Rock Ventures led Synnovation’s Series A financing, which included participation from Nextech, Lilly Asia Ventures, Sirona Capital, and Cormorant Asset Management. Photo by Eli Lilly

BioAge Labs' prioritization of metabolic disease means that other programs are available for partnerships. Until last year, BioAge Labs' progress could be best described as a slow burn, with a pipeline of longevity-focused medicines taking shape incrementally but consistently.  The frenzy around GLP-1s changed all of that, with BioAge’s profile ascending dramatically thanks to being one of a select few biotechs with a combo candidate that might enhance weight loss without muscle loss. Equipped with that potential, and a partnership with Eli Lilly to test the hypothesis, BioAge has closed a $170 million series D led by Sofinnova with contributions from major institutional biotech investors and the venture arms of both the Indianapolis pharma and Amgen.  The financing is enough to last almost three years, at least, CEO Kristen Fortney, Ph.D., said in an interview with Fierce Biotech ahead of Tuesday’s announcement. Atop the to-do list is a phase 2 trial testing lead asset azelaprag with Lilly’s tirzepatide, marketed as Zepbound for weight loss. The primary endpoint of the trial will be weight loss, data Fortney is eager for based on preclinical data she believes should translate well. Fortney hopes that when combined with the low dose of tirzepatide, oral azelaprag can boost patients’ average weight loss reduction from 15% to 20%.  Body composition data will serve as key exploratory endpoints, which if BioAge can even hit just one, would be exciting, Forney added.  The size of the series D and the makeup of the investor group catapult BioAge to the forefront of the metabolic space and set it up to go public in the future. Although the series C was led by a16z (then Andreesen Horowitz), the investor base wasn’t built on a foundation of healthcare specialists. Now it is, with RA Capital, RTW and Longitude Capital all contributing to the series D, among others.  The cash pushes BioAge's cash runway into at least late 2026.  Fortney recognizes that for better or for worse (mainly for better), the internal pipeline is now laser-focused on treating weight loss and obesity, at least in the near term. This deviates a bit from BioAge’s original billing, which was a broader biotech tackling diseases intrinsically tied to aging. The company’s focus at the time of its $90 million series C was two assets for unexplained anemia in elderly patients and COVID-19 in patients without respiratory failure. Both of those assets are now gone from the pipeline, with the study testing COVID med BGE-175 terminated due to too few hospitalizations. BioAge acquired azelaprag from Amgen four months later, in April 2021.  Fortney said the company’s platform has broad applicability in age-related diseases and that BioAge’s focus on metabolic diseases likely tees up business development elsewhere.  “What it does mean is probably we're going to focus more on partnering for other areas as opposed to internal development,” she said. One of those assets is BGE-100, a NLRP3 inhibitor that BioAge believes could help treat neurodegenerative diseases due to neuroinflammation. Toxicology studies are ongoing, and the therapy could enter the clinic around the middle of this year.  The recent transformation of the company into one that has a more linear focus—at least for now—can be neatly packaged as part of a continuous learning experience for Fortney, who co-founded BioAge more than eight years ago. She has grown right alongside the biotech, recognizing that you can’t tackle every disease, and prioritizing is paramount. By doing so, she says she’s found the benefits of diving deeper into one disease area and how relevant targets, like the apelin receptor that’s the focus of azelaprag, may contribute to future therapies.  “That has been a shift over the past year … where I think there's actually a really great match to what our science can do, what our platform can do [and] what our people are excited about,” she said.   Editor's note: This story was updated after a spokesperson corrected the timeline for BGE-100. It could enter the clinic as soon as mid-2024, not mid-2025.