NASDAQ: GPCR

Metabolic Franchise Strategy: Fixed-Dose Combinations and Potential Indication Expansion

Obesity Market

Obesity is a complex, heterogeneous, chronic, and progressive disease, which substantially affects health, quality of life and mortality. “Obesity” and “severe obesity” are defined by a body mass index (“BMI”) of greater than 30 and 40 kg/m2, respectively, with abnormal or excessive fat accumulation. “Overweight” is defined by a BMI of greater than 25 kg/m2.

Obesity has wide-ranging consequences on the health and wellbeing of individuals. The metabolic consequences of obesity include, but are not limited to, T2DM, MASH, hypercholesterolemia, chronic kidney disease, atherosclerotic cardiovascular disease, heart failure, osteoarthritis and sleep apnea. In the United States, 58% of adults with obesity have high blood pressure, a risk factor for heart disease and approximately 23% of adults with obesity have diabetes.

According to the Centers for Disease Control and Prevention, the prevalence of overweight and obesity in the United States between 2017 – 2020 was more than 100 million adults, representing approximately 42% of the population. During the same time, the prevalence of severe obesity was more than 22 million adults, representing approximately 9% of the population. Globally, obesity affects more than 1 billion (16%) adults, with obesity and overweight affecting more than 3 billion people worldwide, and has continued to increase in prevalence worldwide since the World Health Organization declared a global obesity epidemic. This deeply rooted and global health crisis represents a total addressable market of more than $100 billion annually.

Global Obesity Epidemic: Prevalence of Obesity and Overweight and Total Addressable Market

Currently Approved Peptide Treatments have Limitations

Currently approved GLP-1R agonists provide multiple beneficial effects in patients with T2DM, including excellent glycemic control with low risk of hypoglycemia, weight loss and protection against cardiovascular and renal complications. However, approved GLP-1R agonists have several shortcomings in terms of patient convenience, ease of dosing and cost.

Injectable peptide GLP-1R agonists require patients to self-inject, require inconvenient refrigerated storage and are costly. In addition, long acting GLP-1R agonists typically require long titration periods to reach an optimal dose for disease management in order to avoid treatment-associated gastrointestinal side effects, including nausea and vomiting.

Unfortunately, most patients today do not stay on therapy past a year, with discontinuation rates of 65% with injectable GLP-1R agonists after one year and up to 85% after two years as shown below. This means that patients are not benefiting from sustained weight loss and the long-term cardiometabolic benefits that GLP-1R agonist can provide.

Discontinuation Rates of Approved GLP-1R Agonist Treatment Over First Two Year of Treatment

Oral Small Molecules: A Solution for Long-Term Maintenance Therapy

We believe there is a significant opportunity for oral small molecules to enable patients to continue GLP-1R agonist treatment for sustained weight loss and long-term cardiometabolic benefits.

For example, oral semaglutide (Wegovy and Rybelsus), the first approved oral GLP-1R peptide agonist, provides an oral peptide option for patients. However, oral semaglutide requires a stringent dosing protocol and dosing with up to four ounces of water and no food or beverage within 30 minutes. Additionally, the product’s absorption enhancer may affect the absorption of other concomitantly administered oral medications.

Thus, we believe there is a significant unmet medical need for oral small molecule GLP-1R agonists that meet or exceed efficacy and safety parameters of available drugs with less stringent preparation requirements. Existing constraints that should be eliminated or minimized include: restrictive food or fluid dosing protocols, refrigeration and maintenance of effective concentrations throughout the dosing interval without interfering with the absorption of concomitant medications while offering the potential for combination products with other glucose-lowering agents or other commonly co-administered therapies.

In addition, the high prevalence of obesity and overweight together with the broad interest in currently approved GLP-1R peptides have contributed to past drug shortages for Wegovy and Zepbound. Moreover, the scalability of weekly GLP-1R peptide injectables may be limited by fill-finish capacity and device requirements, while the scalability to large populations of oral GLP-1R analog peptides, including oral semaglutide, may be limited by large drug substance requirements arising from their poor bioavailability.

We believe we are well-positioned to overcome the limitations of existing peptide therapies through the development of novel oral small molecule therapeutics via our differentiated technology platform and approach.

Benefits of Oral Small Molecules Versus Oral Peptides

Our Technology Platform and Approach

Our next generation, structure-based drug discovery platform is based on techniques that our founders have evolved over 25 years, which enables us to generate small molecule product candidates designed to overcome the historical limitations of GPCR drug development (see subsection titled “Challenges of GPCR Therapeutics Discovery and Development” below). As shown below, we believe our insights and capabilities for visualizing three-dimensional ligand and target protein structures combined with computational chemistry capabilities of our co-founder and strategic partner, Schrödinger, give us significant competitive advantages in highly efficient and rational drug design. We design our novel compounds by combining our knowledge of GPCR structures together with advanced physics-based computational methods, which we believe allows us to predict the binding affinity of molecules to the target site with a high degree of accuracy.

Our Technology Platform Repeatedly Delivers New Oral Small Molecules

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.

Oral small molecules have large-scale manufacturing advantages and are generally more cost-effective to produce than peptides. We have a current manufacturing capacity of 6,000 tons/year of aleniglipron, which is enough to supply treatment to more than 120 million patients per year.

Our Pipeline and Programs

We pursue opportunities to target GPCRs in human diseases on the basis of validated biology, safety, development feasibility and market potential. We are building a pipeline of wholly-owned oral small molecule drugs targeting chronic diseases with unmet medical need and commercial potential. Our initial focus is in areas of metabolic, cardiovascular and pulmonary diseases.

The following table summarizes key information on our current product candidates:

Our Strategy

Our mission is to discover and develop broadly accessible oral therapeutics to treat a wide range of chronic diseases with unmet medical need through advancements in structure-based drug discovery and computational chemistry. The key pillars of our business strategy to achieve this mission include:

•Advance our lead GLP-1R candidate, aleniglipron, into late stage development. Based on compelling data generated from the ACCESS, ACCESS II, Body Composition, and the ACCESS OLE studies, we believe that aleniglipron has the potential to be a differentiated treatment for obesity and provide a strong foundation to advance into Phase 3 clinical development. We have planned an End-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA) to align on a Phase 3 registrational program with a starting titration dose of 2.5 mg and the intent to evaluate multiple maintenance doses. The Company anticipates initiating the Phase 3 program in the second half of 2026.

•Advance our metabolic franchise including our GLP-1R and amylin backbone therapies, establishing a foundation for additional opportunities. Our franchise approach involves developing next generation GLP-1R and amylin receptor agonists, designed with customized

properties to achieve maximum benefit. Based on preclinical data, we believe that our lead oral small molecule amylin development candidate, ACCG-2671, has the potential to be the first-in-class oral small molecule amylin treatment option for obesity, and we have declared a second amylin development candidate, ACCG-3535. In addition, our program is focused on the development of orally-available small molecules in combination with GLP-1R and/or amylin, including glucose-dependent insulinotropic polypeptide receptor (“GIPR”) and GCG receptor (“GCGR”).

•Invest in and leverage our next generation structure-based drug discovery platform to drive innovations in GPCR targeted therapies and beyond. Our platform has the potential to transform the treatment paradigm for a wide range of chronic diseases with unmet medical need. We are continually growing our position as a leader in structure-based drug discovery and development by incorporating platform innovations that have the potential to expand the therapeutic opportunity of this field. We are integrating advancements in computational chemistry, molecular imaging technologies, structural biology techniques and machine learning while continuing to deepen our understanding of GPCR signaling pathways and pharmacology. We intend to expand into other key emerging areas where we can leverage our platform to develop orally-available molecules against targets that historically have been limited to peptides or biologics.

•Pursue additional opportunities in chronic diseases. Chronic diseases pose a major burden to patients and healthcare systems worldwide and there is an urgent need for effective and more accessible treatment options. We plan to continue to harness insights on GPCR targets, particularly among metabolic, endocrine and cardiovascular indications, and leverage our platform to fuel our pipeline.

•Maximize the potential of our platform and portfolio through strategic partnerships. We have established value- and capability-enhancing collaborations with Schrödinger, our co-founder and strategic partner. We intend to continue to explore additional collaborations with third parties to further strengthen our platform capabilities and enable expansion of our portfolio. We plan to leverage our platform for external opportunities where partners bring additional disease biology understanding, drug development and commercial expertise, regional insights or other complementary capabilities.

Our Programs

Aleniglipron (GSBR-1290) – Oral Small Molecule Selective GLP-1R Agonist for Obesity

Overview and Timeline

Our most advanced product candidate, aleniglipron, is an oral and biased small molecule agonist of GLP-1R, a validated GPCR drug target for obesity, currently in two Phase 2 clinical studies for the treatment of obesity, overweight and related conditions.

We completed our Phase 1 single ascending dose (“SAD”) study of aleniglipron in September 2022. Aleniglipron was generally well tolerated and demonstrated dose-dependent pharmacokinetic (“PK”) and pharmacodynamic (“PD”) activity. We submitted an IND application to the FDA to support initiation of a Phase 1b study in T2DM and obesity and received FDA allowance in September 2022. We initiated the Phase 1b multiple ascending dose (“MAD”) study of aleniglipron in January 2023 and completed dosing in otherwise healthy overweight subjects in March 2023.

In May 2023, we submitted a protocol amendment to the FDA and initiated dosing of the Phase 2a proof-of-concept study in T2DM and obesity. We reported topline data for the 28-day Phase 1b MAD study in September 2023, in which aleniglipron was generally well-tolerated with no adverse event-related discontinuations and demonstrated an encouraging safety profile and significant weight loss of up to 4.9%

placebo-adjusted, supporting once-daily dosing. In December 2023, we reported clinically meaningful topline data from our Phase 2a T2DM cohort, interim results from our Phase 2a obesity cohort and topline data from a Japanese ethno-bridging study of aleniglipron. These data demonstrated that aleniglipron was generally well-tolerated, with no treatment-related serious adverse events (“SAEs”) over 12 weeks, with only one participant discontinuing the study due to adverse events in the T2DM cohort and none in the obesity cohort. Aleniglipron also showed significant reduction in weight in the obesity cohort at 8 weeks and significant reductions in hemoglobin A1c (“HbA1c”) and weight in the T2DM cohort. In June 2024, we reported positive topline data from our Phase 2a obesity study, in which aleniglipron demonstrated a clinically meaningful and statistically significant placebo-adjusted mean decrease in weight of 6.2% at 12 weeks (p<0.0001, using least-squares means (“LSM”) and analyzed based on the primary efficacy estimand using a mixed model for repeated measures) and demonstrated generally favorable safety and tolerability results following repeated, daily dosing up to 120 mg. Furthermore, we explored a new tablet formulation of aleniglipron in a capsule to tablet PK study, which demonstrated a placebo-adjusted mean weight loss of up to 6.9% with the tablet formulation at 12 weeks (p<0.0001, using LSM and analyzed based on the primary efficacy estimand using a mixed model for repeated measures). In July 2024, we submitted an IND to the FDA to support the initiation of a Phase 2b study in chronic weight management and received FDA allowance in August 2024.

In the fourth quarter of 2024, we initiated the Phase 2b ACCESS study, a randomized, double-blind, placebo-controlled, dose-range finding study of aleniglipron in approximately 220 adult participants living with obesity (BMI ≥ 30 kg/m2), or overweight (BMI ≥ 27 kg/m2) with at least one weight-related comorbidity. Participants start at 5 mg of aleniglipron (or placebo) with a 4-week titration schedule, reaching target doses of 45 mg, 90 mg and 120 mg. The primary endpoint is percent change in body weight from baseline to week 36. Secondary endpoints include safety and tolerability of the monthly titration scheme, as well as PK of aleniglipron. In the fourth quarter of 2024, we initiated a randomized, double-blind, placebo-controlled dose-range finding Phase 2 study of aleniglipron, known as ACCESS II, in approximately 82 adult participants living with obesity or overweight with at least one weight-related comorbidity. The study is designed to evaluate two higher doses of aleniglipron. Participants start at 5 mg of aleniglipron (or placebo) and follow a 4-week titration schedule up to target doses of 120 mg, 180 mg and 240 mg. In February 2025, we completed enrollment in the ACCESS and ACCESS II studies, and in December 2025, we reported topline data from the ACCESS clinical program including 36-week topline data from the core Phase 2b ACCESS study, 36-week interim data from the exploratory ACCESS II study, interim data from Phase 2 body composition study and Phase 2b ACCESS open label extension (“OLE”) study. In summary, the Phase 2b ACCESS study demonstrated a placebo-adjusted mean weight loss of 11.3% with 120 mg dose at 36 weeks; the exploratory ACCESS II dose exploration study demonstrated a placebo-adjusted mean weight loss of 15.3% at 240 mg at 36 weeks; and no adverse event-related treatment discontinuations were observed when utilizing the new lower starting titration does of 2.5 mg in the ACCESS Open Label Extension and the Body Composition studies. The Company believes that the data from the ACCESS clinical program supports and informs the advancement to Phase 3 clinical development program in the second half of 2026.

Aleniglipron Design and Discovery

We are developing aleniglipron, a biased oral small molecule GLP-1R agonist, initially as a treatment for obesity and related diseases. Due to its significant preclinical activity and oral availability, we believe that aleniglipron has the potential to be a differentiated treatment with no restrictions on diet or concomitant therapies.

Aleniglipron Analog Bound GLP-1R Cryo-EM Structure

Aleniglipron was designed through our internal structure-based drug discovery platform. As shown above, multiple small molecules bound to GLP-1R structures have been generated to guide iterative chemistry design efforts. Aleniglipron is also designed to be a biased GPCR agonist, which only activates the G-protein pathway without β-arrestin signaling at therapeutic doses, thereby avoiding receptor internalization and de-sensitization. In an intravenous glucose tolerance test in non-human primates (“NHPs”), aleniglipron increased glucose-dependent insulin secretion to a similar level achieved by liraglutide, an approved injectable GLP-1R agonist. In a repeat food intake study in NHPs, aleniglipron showed a significant decrease in body weight relative to the placebo and surpassed that seen with liraglutide.

Aleniglipron Non-clinical Safety Pharmacology and Toxicology Studies

A standard battery of nonclinical safety pharmacology studies (central nervous system, cardiovascular and respiratory) has been completed with aleniglipron with no findings anticipated to be of clinical relevance. Genotoxicity assessments demonstrated an absence of genotoxicity potential.

In the 4-week and 13-week GLP toxicology study in rats, the no-observed-adverse-effect level (“NOAEL”) dose was considered to be 1000 mg/kg/day, the highest dose tested. In the 4-week and 13-week GLP toxicology study in NHPs, aleniglipron showed pharmacologically related events such as inappetence and bodyweight loss, which were reversible with sufficient recovery periods. There were no aleniglipron related deaths during the course of study and no aleniglipron related changes in organ weights, gross and histopathology examinations at the end of the dosing and recovery periods. In the 13-week study, NHPs of both sexes in all dose groups, including in the control group, had minimal to moderate multifocal necrosis/infiltration in the liver. The root cause of these liver abnormalities was not determined, but these findings were considered unrelated to aleniglipron. The FDA reviewed our 13-week GLP toxicology studies in rats and NHPs and agreed that these liver abnormalities were not considered a new non-clinical safety signal related to aleniglipron.

In nonclinical animal models, aleniglipron demonstrated statistically significant decreases in blood glucose concentration and increases of insulin secretion.

In a recent 6-month GLP toxicology study in rats, aleniglipron demonstrated a NOAEL dose at 1000 mg/kg/day, which supports an estimated more than 100-fold safety window up to 120 mg human dose. We also conducted a 9-month NHP GLP toxicology study and found no test article-related change in heart rates or QTc intervals. No meaningful increases in the liver enzymes, ALT/AST, were observed in either the rat or

NHP study. There were no significant findings in embryo-fetal developmental toxicology studies in rats and rabbits.

Aleniglipron Phase 2a Study in Obesity and Diabetes

In June 2024, the Company reported positive topline data from the Phase 2a obesity study in which GSBR-1290 demonstrated a clinically meaningful and statistically significant placebo-adjusted mean weight loss of 6.2% at 12 weeks (p<0.0001) and generally favorable safety and tolerability results following repeated, daily dosing up to 120 mg. The Company also reported data from a new tablet formulation of GSBR-1290 in a capsule to tablet PK study, which demonstrated a placebo-adjusted mean weight loss of up to 6.9% with the tablet formulation at 12 weeks. PK data support proportional exposure between 60 and 120 mg and once-daily oral dosing of GSBR-1290.

Phase 2b ACCESS study — Evaluating target doses of up to 120 mg

The core 36-week Phase 2b ACCESS study was a randomized, double-blind, placebo-controlled, Phase 2b dose- range finding clinical study that enrolled 230 adult participants living with obesity (body mass index (BMI) ≥ 30 kg/m2), or overweight (BMI ≥ 27 kg/m2) with at least one weight-related comorbidity. Participants were enrolled in 36 participating sites across the United States. Participant ages ranged from 49 to 52 years and participants were predominantly female (53% to 55%) with a baseline BMI of 39. HbA1c and blood pressure, according to the eligibility criteria, were within normal limits. All participants were randomized 3:1 (active:placebo) and started at 5 mg of aleniglipron (or placebo) with a 4-week titration schedule, reaching target doses of 45 mg, 90 mg or 120 mg once-daily.

Each of the three doses in the ACCESS study achieved statistical significance on the primary endpoint and all key secondary endpoints. Primary efficacy estimand1 results at 36 weeks are shown below:

Aleniglipron

Aleniglipron

Aleniglipron

​ ​ ​

45 mg

​ ​ ​

90 mg

​ ​ ​

120 mg

​ ​ ​

Placebo

Mean percent change in body weight at 36 weeks compared to baseline

-9.0

-10.7

-12.1

-0.8

Placebo-adjusted mean percent change in body weight at 36 weeks compared to baseline

-8.2

-9.8

-11.3

—

P-value

p<0.0001

p<0.0001

p<0.0001

—

1 The primary efficacy estimand represents efficacy had all randomized participants remained on study treatment (with possible dose interruptions and/or dose modifications) for 36 weeks without initiating rescue weight management treatments or surgeries.

At week 36, key secondary endpoints in the study show that 86% of participants in the aleniglipron 120 mg dose cohort achieved at least 5% weight loss and 70% achieved at least 10% weight loss. In addition, aleniglipron demonstrated clinically meaningful improvements in systolic blood pressure (-6.4 to -7.5 mmHg) and HbA1c (-0.28% to -0.37%).

Aleniglipron demonstrated a tolerability profile consistent with the GLP-1 receptor agonist class following repeated, once-daily dosing of up to 120 mg in the Phase 2b ACCESS study. As expected for the GLP1-RA drug class, the most common AEs were gastrointestinal (“GI”)-related and the two most common AEs in the titration phase were nausea and vomiting. AEs were generally observed early in treatment. In the Phase 2b ACCESS study, the AE-related treatment discontinuation rate ranged from 7.7% – 13.3% between all doses, with a mean 10.4% across all active arms in the study.

Exploratory ACCESS II Study — Evaluating higher doses up to 240 mg

ACCESS II is a randomized, double-blind, placebo-controlled, clinical study of aleniglipron that enrolled 85 adult participants living with obesity, or overweight with at least one weight-related comorbidity. Participants were enrolled in ten sites across the United States. The study was designed to evaluate two higher doses of aleniglipron. Participants started at 5 mg of aleniglipron (or placebo) and followed a 4-week titration schedule up to target doses of 120 mg, 180 mg and 240 mg. Twelve participants were part of the sentinel group which aimed to provide preliminary data at the 180 mg/day dose to the independent data monitoring committee before moving to higher doses in the main part of the study, which included 73 participants, 61 allocated to aleniglipron and 12 to placebo. At week 28, the remaining participants at 120 mg of aleniglipron were re-randomized to stay on 120 mg, titrate to 180 mg, or titrate to 180 mg to ultimately reach 240 mg. The 44-week study remains ongoing with data from a prespecified 36-week analysis currently available. At 36 weeks, each of the three dose cohorts in the ACCESS II study met statistical significance compared to placebo. Primary efficacy estimand results at 36 weeks are shown below:

Aleniglipron

Aleniglipron

Aleniglipron

​ ​ ​

120 mg

​ ​ ​

180 mg

​ ​ ​

240 mg

​ ​ ​

Placebo

Mean percent change in body weight at 36 weeks compared to baseline

-13.1

-13.3

-14.2

+1.0

Placebo-adjusted mean percent change in body weight at 36 weeks compared to baseline

-14.1

-14.4

-15.3

—

P-value

p<0.0001

p<0.0001

p<0.0001

—

Aleniglipron demonstrated a tolerability profile consistent with the GLP1-RA class following repeated, once- daily dosing of up to 240 mg. As expected for the GLP1-RA drug class, the most common AEs were

gastrointestinal (GI)-related and the two most common AEs in the titration phase were nausea and vomiting. AEs were generally observed early in treatment.

Topline 44-week data from the ACCESS II study are expected in the first quarter of 2026.

Body Composition Study — Evaluating lower 2.5 mg starting dose

The Company is currently conducting a randomized, placebo-controlled body composition study that enrolled 71 adult participants to assess the effect of aleniglipron (up to 120 mg) on body fat loss over a 40-week evaluation period. Participants with similar eligibility criteria to the previous studies were enrolled in 11 sites in the United States. 59 participants were randomized to the aleniglipron treatment arm, started at a 2.5 mg dose, and titrated up monthly to a target dose of 120 mg. Data from a pre-specified interim analysis after a median follow-up time of approximately 10 weeks showed that starting at a lower dose of 2.5 mg for the first four weeks meaningfully improved tolerability compared to what was observed at a starting titration dose of 5 mg in the ACCESS and ACCESS II studies, with no AE-related treatment discontinuations observed at the initial 2.5 mg dose or the subsequent 5 mg dose. Topline data from the study are expected in the second half of 2026.

ACCESS OLE Study — Following randomized 36-week period, evaluating lower 2.5mg starting dose

Following the 36-week randomized controlled portion of the Phase 2b ACCESS study, the majority of eligible ACCESS participants enrolled in ACCESS OLE, which provides an additional 36 weeks of treatment with aleniglipron. An initial analysis from the ongoing OLE demonstrates continuing weight loss in all dose cohorts out to 44 weeks, showing no evidence of weight loss plateau and proportional pharmacokinetic exposure up to 240 mg as shown below:

In the ACCESS OLE study, participants who received placebo in the initial double-blind portion transitioned to aleniglipron at a starting dose of 2.5 mg and titrate monthly to a target dose of 120 mg. Initial data from this group of participants after eight weeks of treatment are consistent with the findings from the body composition study, showing that starting at a 2.5 mg titration dose meaningfully improved tolerability compared to what was observed in the starting 5 mg titration dose in ACCESS and ACCESS II studies, with no AE-related

treatment discontinuations at the initial 2.5 mg or the subsequent 5 mg dose. Topline data from the OLE study are expected in the second half of 2026.

Aleniglipron Safety

Aleniglipron demonstrated a compelling safety profile across all studies. Importantly, there were no cases of drug-induced liver injury, no persistent liver enzyme elevations (as shown below), and no QTc prolongation across all aleniglipron studies.

Phase 3 Preparation

Data from ACCESS, ACCESS II, body composition, and the ACCESS OLE studies provide a strong foundation to advance aleniglipron into Phase 3 clinical development. The Company has plannned an End-of-Phase 2 meeting with the U.S. Food and Drug Administration to align on a Phase 3 registrational program with a starting titration dose of 2.5 mg and the intent to evaluate multiple maintenance doses. The Company anticipates initiating the Phase 3 program in the second half of 2026.

In addition to the expected data from the body composition and ACCESS OLE described above, the Company expects to report topline results from its maintenance switching study evaluating the transition from an approved injectable GLP1-RA injectable to aleniglipron for weight loss maintenance, its Phase 2 randomized placebo controlled study assessing aleniglipron at doses of up to 240 mg in patients living with obesity or overweight and type 2 diabetes mellitus, in the second half of 2026.

ACCG-2671 and ACCG-3535 – Oral Small Molecule Amylin Receptor Agonist for Obesity

Overview

We are advancing our amylin oral small molecule program and have initiated a Phase 1 clinical study of our lead candidate, ACCG-2671 in December 2025. In addition, we declared a second development candidate, ACCG-3535. In preclinical studies, ACCG-2671 and ACCG-3535 demonstrated sub-nanomolar in vitro functional activity on amylin and calcitonin receptors, and in vivo reduction in food intake, resulting in weight loss. We expect to report initial Phase 1 study results for ACCG-2671 and to initiate a Phase 1 study for ACCG-3535 in the second half of 2026.

The amylin receptor system is complex, and its complexity is present at various levels as shown here and in the figure below:

•First (starting from left figure panel): At the receptor level, there are three amylin receptors, AMY1/2/3 receptors. They are heterodimers formed by the calcitonin receptor CTR and the co-receptor RAMP1/2/3. There is an equilibrium between calcitonin receptor and Amylin receptors.

•Second: At the agonist level, there are two types of agonists: DACRA and SARA

o

DACRA, stands for Dual Amylin and Calcitonin Receptor Agonists, which binds both the amylin receptor and calcitonin receptor.

o

SARA, stands for Selective Amylin Receptor Agonist, which preferentially binds to the amylin receptor.

•Third: Different agonists bind to the amylin receptor or calcitonin receptor and form different receptor-agonist complexes. These complexes could differ in stability, conformation, G protein/b-arrestin recruitment and activation status and cAMP signaling.

The amylin receptor pocket is large, making small molecule discovery challenging.

The amylin receptor pocket is large, making small molecule discovery challenging. Despite these challenges, we have successfully discovered what we believe is the first amylin small molecule agonist.

Amylin is co-secreted with insulin from β pancreatic cells upon nutrient delivery to the small intestine as a satiety signal, acts upon sub-cortical homeostatic and hedonic brain regions, slows gastric emptying and suppresses post-prandial glucagon responses to meals. Therefore, new pharmacological amylin analogues can be used as potential anti-obesity medications in individuals who are overweight or obese.

Amylin Tool Compound Showed Add-on Effects When Used with Semaglutide

In collaboration with Schrödinger, we are taking a structure-based drug discovery approach to identify oral small molecule amylin agonists for daily use either alone or in combination with GLP-1R agonists to treat obesity and T2DM. In an in-house proof-of-concept study in rats, our small molecule amylin tool compound (ACCG-0184) showed additional beneficial effects when used as an add-on treatment to a GLP-1R agonist.

In December 2024, we announced the selection of ACCG-2671 as our lead oral amylin agonist for the treatment of obesity, which is designed as an oral small molecule DACRA. We have initiated Phase 1 clinical development in December 2025 and expect to receive Phase 1 study results in the second half of 2026. In addition, we have initiated GMP manufacturing to support GLP toxicology studies and early clinical development.

Preclinical ACCG-2671 data demonstrated high binding affinity and balanced potency in human calcitonin receptor and amylin receptor functional assays. In diet-induced obese rats, oral administration of ACCG-2671 resulted in significant, dose-dependent body weight reductions. Combination therapy with semaglutide (both as a subsequent add-on to semaglutide and as a concurrent treatment) resulted in superior weight loss compared to ACCG-2671 monotherapy.

ACCG-2671 Demonstrated Sub-nanomolar Potency of DACRA Activity

ACCG-2671 Achieved Cagrilintide-like Efficacy in Preclinical DIO Rat Model

In November 2025, we selected a second DACRA development candidate, ACCG-3535. ACCG-3535 is a unique chemical structure from ACCG-2671. Preclinical ACCG-3535 data indicated high binding affinity to human amylin and calcitonin receptors and balanced potency in human amylin and calcitonin receptor functional assays. In addition, ACCG-3535 demonstrated robust food intake suppression and significant, dose-dependent body weight reduction as a monotherapy in diet-induced obese rats. Combination therapy with semaglutide (both concurrently and as a subsequent add-on to semaglutide) resulted in superior weight loss compared to semaglutide or ACCG-3535 monotherapy.

Lastly, given our most advanced oral small molecule amylin position, we are continuing to work on multiple generations, and we expect to declare additional development candidates in the future.

GIP and GCG Receptor Oral Small Molecule Obesity Programs

Overview

Beyond our GLP-1R and amylin receptor programs, we are developing next generation oral incretins for potential combination therapy with GLP-1R or amylin candidates. These include small molecule candidates targeting GIPR and GCGR, each designed with customized properties to achieve additional benefit.

In our GIPR program, we have identified multiple GIPR agonist, dual GLP-1R/GIPR agonist and GIPR antagonist hits for small molecule GIPR modulation. We believe GLP 1R/GIPR modulation has the potential to provide a differentiated treatment in obesity.

Recent third-party clinical data showed tirzepatide, a GLP-1R/GIPR modulator, was superior to semaglutide with respect to glycemic control. The glycated hemoglobin level target of less than 5.7% (normoglycemia) was

met in 27% to 46% of the T2DM patients who received tirzepatide compared to 19% of those who received semaglutide. The body weight reduction and gastrointestinal-related side effects were similar to the GLP-1R agonists. In addition, many patients who received tirzepatide were noted to have improved biomarkers of insulin sensitivity.

We have obtained both GIP and tirzepatide bound GIPR structures along with GLP-1R structures to guide our small molecular design.

Multiple Structures of Ligand Bound GLP-1R, GIPR, GCGR

As shown above, representative three-dimensional structures of the incretin GPCRs (e.g., GIPR, GLP-1R, Glucagon receptor) are available for structure-based drug discovery. This structural data enables the design of dual and tri modulators of this important class of metabolic GPCRs. The GIPR model shown below suggests that one of our dual GLP-1/GIPR agonists may extend to fill the pocket (highlighted in color) occupied by our GLP-1/GIPR agonist hits. Multiple approaches were applied for hit identification, including a screen of our proprietary incretin compound library. Weak antagonists and agonists were identified. After several rounds of structure activity relationship evolution, a full potential GLP-1R/GIPR antagonist and initial dual GLP-1R/GIPR agonist hit leading to the discovery of an optimized dual GLP-1R/GIPR agonist hit. While displaying different GIPR activity, both compounds still maintained certain levels of GLP-1R activities.

GIPR Agonist/dual Agonist/antagonist Hits Identified for Potential GLP-1R Combinations

In our GCG program, we have identified multiple GCGR agonist and dual GLP-1R/GCGR agonist hits for small molecule GCGR modulation. GCG is primarily expressed in the liver and therefore GCGR agonists could play an important role in liver-mediated diseases, specifically MASH.

ANPA-0073- Oral Small Molecule APJ Receptor Agonist

ANPA-0073 is our biased APJ receptor agonist that we were previously developing for pulmonary arterial hypertension and idiopathic pulmonary fibrosis. Given the APJ receptor mechanism of action in regulating energy metabolism to promote selective weight loss and reduce fat mass without severe muscle loss, we evaluated ANPA-0073 as a potential combination with weight loss medicines for selective or muscle-sparing weight loss. In September 2022, we completed a Phase 1 single and multiple ascending dose clinical study evaluating ANPA-0073 in healthy human volunteers, in which it was generally well tolerated up to 500 mg. In 2025, we had also conducted long term GLP-toxicology studies of ANPA-0073 and have decided that it was not suitable for selective weight loss and have prioritized the development of our other discovery stage APJ receptor agonists, which we believe may provide more selective weight loss or muscle-sparing weight loss, potentially as combination therapies.

LTSE-2578 – Oral Small Molecule LPA1R Antagonist for IPF

We have been developing an antagonist that targets lysophosphatidic acid 1 receptor (“LPA1R”), a GPCR implicated in responses to tissue injury and pro-fibrotic processes, for the treatment of idiopathic pulmonary fibrosis (“IPF”).

We believe LTSE-2578 is a differentiated oral small molecule because it demonstrated potent in vitro and in vivo activity in preclinical IPF models and dose dependent inhibition of histamine release as the pharmacodynamic marker. We have completed IND-enabling studies including 28-day GLP-toxicology studies in dogs and rats. In July 2025, we completed a Phase 1 single and multiple ascending dose clinical study of LTSE-2578, our oral small molecule antagonist that targets the lysophosphatidic acid 1 receptor (“LPA1R”) for the treatment of IPF. The randomized, double-blind, placebo-controlled first-in-human clinical study investigated the safety, tolerability and pharmacokinetics of single and multiple ascending doses of LTSE-2578. In the study, there were no evidence of any dose-dependent LTSE-2578-related adverse events, including clinical, laboratory and electrocardiogram recordings. No serious adverse events were observed. Having completed the Phase 1 study, we are considering strategic alternatives for LTSE-2578 as a Phase 2 ready program in non-metabolic indications.

GPCRs as a Therapeutic Target Family

GPCRs form the largest human membrane protein family, consisting of approximately 800 identified members as illustrated below. GPCRs are involved in several vital physiological functions, such as immune system regulation and inflammation, autonomic nervous system transmission, behavioral and mood regulation, sensory transmission and maintenance of homeostasis. Therefore, they are important targets for numerous therapeutics with approximately 475 drugs on the market to date acting at over 100 unique GPCRs. Importantly, more than 220 GPCRs have not yet been explored as clinical targets, hence representing a broad and untapped therapeutic potential for addressing global healthcare needs.

Phylogenetic Tree of GPCR Targets

GPCR targeting drugs have successfully delivered significant patient benefit resulting in large market opportunities in many therapeutic areas. Examples include liraglutide (Victoza for T2DM), aripiprazole (Abilify for schizophrenia, bipolar disorder and depression), montelukast (Singulair for asthma), valsartan (Diovan for hypertension), metoprolol (Lopressor for hypertension, angina and myocardial infarction) and clopidogrel (Plavix for myocardial infarction and stroke). GPCR related drugs are the largest drug class accounting for approximately 27% of global pharmaceutical sales with estimated aggregate sales of $890 billion between 2011 and 2015.

GPCRs are proteins that span the entire width of cell membranes. Their primary function is to recognize extracellular substances, primarily ligands, and transmit signals across the cell membrane to the inside of the cell.

Schematic of a GPCR

As shown above, the binding of extracellular ligands to GPCRs elicits conformational changes that impact the intracellular side of the receptor, resulting in the formation of a GPCR complex with signal transducers, particularly G-proteins. These signal transducers go on to interact with second messengers, ultimately either stimulating or inhibiting certain cellular processes.

GPCRs signal not only through G-proteins, but also through β-arrestins and other non-G-protein transducers. Β-arrestins play an essential role in many physiological and pathological processes, and they are involved in the desensitization, internalization, sequestration and trafficking of GPCRs. Certain GPCR ligands are capable of simultaneously activating both G-protein and non-G-protein mediated signaling pathways, which can lead to a variety of physiologic as well as pathologic effects.

Challenges of GPCR Therapeutic Discovery and Development

Despite tremendous advancements in structure-based drug design and development, GPCR drug discovery and development remains challenging.

•Similarity between the binding sites of GPCRs and related receptors can cause off-target toxicities: All GPCRs have the same overall three-dimensional architecture but the specific endogenous binding site is unique due to the placement of amino acid side chains shaping the binding site. For instance, the early sphingosine 1 phosphate 1 receptor (“S1P1R”) agonist Gilenya led to the development of a new class of therapy for the treatment of multiple sclerosis, but had exhibited bradycardia as a side effect due in part to sphingosine 1 phosphate 3 receptor (“S1P3R”) activity, a very closely related S1P1 receptor subtype. The next generation S1P1R agonist Zeposia was designed using structural information by Receptos, Inc. to remove the S1P3 and other activities and therefore did not have the same side effect profile as Gilenya.

•GPCRs are involved in diverse downstream signaling pathways which can result in side effects: GPCRs interact with a range of molecules, including G-protein and non-G-protein transducers including β-arrestin. Signaling pathway selectivity results from agonist-induced specific receptor conformation and when targeting GPCRs involved in multiple signaling pathways, both therapeutic benefits and side effect issues may arise.

•Expression levels of GPCRs are low and create significant hurdles to structural and PD characterization: Recombinant protein expression of GPCRs remains extremely challenging. Expression levels of GPCRs are low and improvement of expression level continues to be mainly empirical and resource-consuming. GPCRs are complex membrane proteins that require a stable membrane environment throughout the purification process to avoid destabilization and aggregation.

•GPCR structural visualization is complex making GPCR structure-based drug discovery challenging: Structure-based drug design requires rapid iterations of GPCR structures in complex with specific new ligands to determine their effects on conformation. This is well established through robust crystallography platforms for soluble drug targets. Cryo-EM has helped accelerate the membrane protein field, but the methods still require substantial expertise and execution.

Drug discovery approaches targeting GPCRs have evolved from traditional approaches including high throughput screening to rational design for enhanced activity, tailor-made signaling response and improved selectivity, which leads to improved safety and tolerability profiles.

Our Structure-Based Drug Discovery Technology Platform

Our platform is based on techniques that our founders have been evolving for over 25 years, which have enabled them to deliver multiple marketed medicines. Our approach enables us to generate small molecule product candidates that are designed to overcome the historical limitations of GPCR drug development.

Our insights and capabilities enable us to visualize the three-dimensional protein structures of the target and the ligands. We believe this visualization combined with the computational chemistry capabilities of Schrödinger gives us significant competitive advantages in highly efficient and rational drug design. We design our novel compounds by combining our knowledge of GPCR structures together with advanced physics-based computational methods, which we believe allows us to predict the binding affinity of molecules to the target site with a high degree of accuracy.

As shown below, our technology platform allows us to determine feasibility, optimize the design of and efficiently generate families of potent and highly selective small molecule candidates.

Structure Therapeutics Integrated Technology Platform from Target to IND

Oral small molecules have the potential to address the key limitations of biologic and peptide drugs, such as high cost and patient inconvenience, thereby significantly improving patient access. We believe this is particularly important for the most prevalent chronic diseases including those involving the endocrine, cardiovascular and pulmonary systems. We believe the strengths of our technology platform will enable us to develop oral small molecule drugs that can deliver biologic-like activity and specificity.

GPCR Target Prioritization

We start with target prioritization by focusing on validated GPCR targets that do not have attractive small molecule solutions. We then prioritize by assessing the feasibility of a small molecule solution for these targets and market opportunities of their respective target indication.

Expertise in GPCR Structure-Based Drug Discovery

GPCRs are difficult to characterize structurally because they are composed of seven transmembrane domains, have low expression and are unstable outside of the cell membrane environment. While structure-based approaches have been utilized for decades in soluble protein drug discovery, recent breakthrough advancements in computational chemistry, artificial intelligence, machine learning and electron microscopy are redefining the field of GPCR structure-based drug discovery.

Visualization of GPCR Structure and Binding Site Interactions

As shown above, our structure-based technology platform combines direct visualization of protein receptor binding interactions with advanced simulation of molecular motion and signal transduction. Site 1 is considered to be the orthosteric or primary binding site for receptor activation. Site 2 is on the surface of the receptor, often referred to as the allosteric site and may potentially regulate receptor activation signaling. By visualizing and analyzing how different ligands bind to a particular target and specific sites and affect their conformational dynamics, we believe we are able to efficiently convert biologics and peptides into more accessible, patient-accommodating oral small molecules. In addition, we can enhance the pharmaceutic properties of our small molecules with the aim of eliciting the desired function while maintaining superior pharmaceutical properties.

Non-biased vs Biased GPCR Agonists

Additionally, GPCR signaling can follow several pathways and molecules can be designed such that their pharmacology is selected to create “biased signaling” as illustrated above. GPCRs are known to signal not only through G-proteins, but also through β-arrestins, intracellular proteins that “arrest” the signal and stop the receptor from becoming over-stimulated through a receptor internalization mechanism. Using the three-dimensional structures of GPCRs and selection methods, we can potentially design highly selective “biased”

molecules that preferentially activate G-protein and not β-arrestin pathways, which could lead to enhanced clinical activity as well as an improved safety profile due to lower dosage requirements.

Robust and Integrated Medicinal Chemistry to Generate and Optimize Hits on GPCR Targets

We have extensive medicinal chemistry know-how on the discovery and development of novel molecules that target GPCRs. When coupled with our deep understanding of GPCR biology, we have the potential to design appropriate chemotypes for each GPCR function as illustrated below.

Family Members with Determined Structures are Highlighted within the Tree, and their Binding Pockets with the Ligand

Four Character Code at End of Each Image is Protein Data Bank ID.

Further optimization of compounds powered by our excellence in medicinal chemistry led us to identify potent and selective oral small molecule product candidates.

Partnership with Schrödinger Leveraging its Cutting-Edge Computational Chemistry Capability

We have collaborations with Schrödinger on the iteration and optimization of GPCR lead compounds using various next-generation physics-based computational technologies. Schrödinger is a scientific leader in chemical simulation, accurate physics-based methods, which includes among many technologies, FEP and in silico drug discovery. Its’ computational platforms integrate predictive physics-based methods with machine learning to evaluate billions of compounds in silico, achieving experimental accuracy on properties such as binding affinity and solubility. Through this iterative process, we can accelerate evaluation and optimization of molecules in silico ahead of synthesis and assay and then further optimize them through additional cycles of computation analysis.

Structure Therapeutics Integrated Platform

As shown above, our collaborations with Schrödinger in our computational and chemistry module enables us to accelerate our lead optimization drug discovery process and reduce development costs. In our partnership with Schrödinger on GPCR drug discovery, we retain the full product rights on the compounds under development.

Safety Assays

We have proactively used cell and animal-based safety assays to better screen out unwanted side effects, such as liver, cardiovascular and central nervous system toxicity at the initial stages of lead optimization, and we have designed molecules to help minimize safety risks at every step. Our in-depth understanding of GPCR signaling pathway provides us insights to design biased molecules when necessary to mitigate any unwanted liabilities while maintaining the desired activities.

Other Proprietary In-House Development Tools for Drug Synthesis and Screening

In addition to our robust iterative structure-based drug discovery platform shown above, Basecamp Bio is optimizing proprietary in-house drug discovery tools including DNA-Encoded Library technology and Affinity Mass Spectrometry technology to enable the synthesis and screening of vast numbers of small molecule product candidates at a scale that is not possible to achieve by traditional methods.

Intellectual Property

Our success depends in part on our ability to obtain and maintain proprietary protection for our product candidates and other discoveries, inventions, trade secrets and know-how that are critical to our business operations. Our success also depends in part on our ability to operate without infringing the proprietary rights of others, and in part on our ability to prevent others from infringing our proprietary rights. A comprehensive discussion on risks relating to intellectual property is provided under Part I.