Zastaprazan: A Comprehensive Clinical and Pharmacological Profile

I. Introduction to Zastaprazan

A. Overview of Zastaprazan as a Novel Acid-Suppressive Agent

Zastaprazan is a novel, orally administered potassium-competitive acid blocker (P-CAB) developed for the treatment and prevention of acid-related gastrointestinal disorders. It represents a new generation of acid-suppressive therapy, aiming to address limitations of existing treatments such as proton pump inhibitors (PPIs).[1] The development focus on characteristics like faster onset of action and food-independent dosing directly targets known drawbacks of PPIs, suggesting a strategic approach to capture market share by offering enhanced convenience and potentially more consistent acid control.[5] This approach is particularly relevant as the P-CAB class is positioned to offer tangible improvements in a mature acid-suppression market. By demonstrating non-inferiority to standard PPIs, with trends towards faster action, Zastaprazan aims to establish itself as a significant therapeutic option. The emphasis on food-independent dosing and rapid onset addresses patient convenience and adherence, critical factors in managing chronic acid-related conditions.

B. Developer and Originator Information

Zastaprazan was developed by Onconic Therapeutics Inc., a clinical-stage biopharmaceutical company based in South Korea.[1] Onconic Therapeutics is a subsidiary of Jeil Pharmaceutical Co., Ltd..[12] Notably, Onconic Therapeutics is distinguished as the only biotech firm in Korea to have secured regulatory approval and commercialized a new drug prior to its public listing, highlighting its research and development capabilities.[21]

C. Chemical Identity and Alternative Names

The International Nonproprietary Name (INN) for the compound is Zastaprazan.[2] Throughout its development, it has been referred to by several codes, most prominently JP-1366 [1], and also OCN-101.[13] In South Korea, it is marketed under the brand name Jaqbo®.[1] The compound is often referred to as Zastaprazan citrate in regulatory and development contexts.[5]

Table 1: Zastaprazan - Key Drug Information

Feature	Detail	Reference(s)
INN	Zastaprazan	2
Development Codes	JP-1366, OCN-101	1
Brand Name (Korea)	Jaqbo®	1
Developer	Onconic Therapeutics Inc.	1
Originator/Parent	Jeil Pharmaceutical Co., Ltd.	16
Chemical Class	Synthetic organic; Azetidine; Imidazole; Methylamine; Pyridine	1
CAS Number	2133852-18-1	32
Molecular Formula	C22H26N4O	32
Molecular Weight	362.47 g/mol	1
IUPAC Name	azetidin-1-yl-[(2,6-dimethylphenyl)methylamino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl]methanone	2
Formulation	Zastaprazan citrate (common)	13

II. Mechanism of Action and Pharmacological Class

A. Zastaprazan as a Potassium-Competitive Acid Blocker (P-CAB)

Zastaprazan is classified as a potassium-competitive acid blocker (P-CAB), a newer class of pharmacological agents designed for potent gastric acid suppression.[1] These agents act by directly inhibiting the gastric H+/K+-ATPase, commonly known as the proton pump, which is the enzyme responsible for the final step in the secretion of gastric acid by parietal cells in the stomach.[1]

B. Molecular Target: H+/K+-ATPase Inhibition

The primary molecular target of Zastaprazan is the H+/K+-ATPase enzyme. Zastaprazan exerts its acid-suppressive effect by competitively binding to the potassium-binding site of this enzyme.[7] This binding is reversible and effectively blocks the exchange of intracellular H+ ions for extracellular K+ ions, thereby inhibiting the secretion of gastric acid into the gastric lumen.[1] The reversible and direct competitive binding to the H+/K+-ATPase distinguishes P-CABs from PPIs. This fundamental difference allows P-CABs to inhibit both active and resting proton pumps immediately upon reaching them, without the need for acid-mediated activation, which underpins their characteristic faster onset of action and potentially more predictable acid suppression profile.[1]

C. Comparative Pharmacology: Advantages and Differences versus Proton Pump Inhibitors (PPIs)

Zastaprazan and other P-CABs offer several pharmacological distinctions and potential advantages over the traditional PPIs:

• Mechanism and Activation: P-CABs, including Zastaprazan, directly and reversibly inhibit the H+/K+-ATPase by competing with K+ ions at the luminal surface of the parietal cell. In contrast, PPIs are prodrugs that require accumulation in the acidic canaliculi of parietal cells and subsequent acid-mediated conversion to their active form, which then binds covalently and irreversibly to the proton pump.[7]
• Onset of Action: Due to their direct mechanism of action, P-CABs like Zastaprazan typically exhibit a more rapid onset of acid suppression compared to PPIs. Zastaprazan has been shown to achieve significant acid inhibition within the first hour of administration.[5]
• Potency and Duration of Acid Suppression: P-CABs generally provide more profound and sustained acid suppression. Zastaprazan, for instance, can maintain intragastric pH above 4 for approximately 85% of a 24-hour dosing interval.[8] This sustained effect may be particularly beneficial in managing conditions like nocturnal acid breakthrough, a common limitation of PPI therapy.
• Food Effect: A significant practical advantage of Zastaprazan is its food-independent dosing. It can be taken with or without meals without a significant impact on its efficacy, offering greater convenience and potentially better adherence for patients compared to many PPIs, which often require administration 30-60 minutes before a meal for optimal effect.[5]
• Metabolism and Inter-individual Variability: As detailed in Section III, Zastaprazan's pharmacokinetic profile is not significantly influenced by CYP2C19 genetic polymorphisms.[3] This contrasts with several PPIs, whose metabolism is dependent on CYP2C19, leading to inter-individual variability in drug exposure and clinical response.
• Clinical Implications: These pharmacological differences suggest that P-CABs may offer advantages in clinical scenarios requiring rapid and consistent acid control, such as in patients with severe erosive esophagitis needing quick symptom relief, individuals with unpredictable meal schedules, or those known to be poor or rapid metabolizers of CYP2C19-dependent PPIs.[7] The more consistent 24-hour acid suppression provided by Zastaprazan could also translate into better management of nocturnal GERD symptoms and potentially improved outcomes in patients with extraesophageal manifestations of GERD, areas where PPIs have shown limitations.[8]

III. Pharmacokinetic Profile

A. Population Pharmacokinetic (PK) Modeling and Characteristics

The pharmacokinetic behavior of Zastaprazan has been characterized through population PK modeling. These analyses indicate that Zastaprazan's plasma concentration-time profile is best described by a two-compartment model. The absorption phase is characterized by an Erlang-type absorption model, specifically involving six sequential compartments, which suggests a more complex absorption process than simple first-order kinetics, possibly reflecting a delay or multiple steps in absorption. Elimination of Zastaprazan follows first-order kinetics.[3] This comprehensive model has been validated and has shown to adequately describe the observed PK of Zastaprazan in both healthy volunteers and patients diagnosed with GERD.[3]

B. Influence of Covariates on Pharmacokinetics

Several patient-specific factors (covariates) have been evaluated for their potential impact on Zastaprazan's pharmacokinetics:

• CYP2C19 Phenotypes: A significant finding from population PK studies is that the genetic polymorphisms of the cytochrome P450 2C19 (CYP2C19) enzyme do not have a clinically significant effect on the pharmacokinetics of Zastaprazan.[3] This is a crucial differentiating factor from many PPIs, whose metabolism and efficacy can be substantially altered by an individual's CYP2C19 genotype (e.g., poor, intermediate, extensive, or ultra-rapid metabolizers). Zastaprazan's independence from this metabolic pathway suggests more predictable drug exposure and therapeutic response across diverse patient populations, potentially simplifying dosing and reducing the need for genotype-guided therapy adjustments.
• Disease Status (GERD): The presence of GERD was identified as a statistically significant covariate influencing the apparent clearance (CL/F) of Zastaprazan. Specifically, patients with GERD exhibited lower clearance values compared to healthy volunteers.[3] However, despite this observed difference in clearance, subsequent model-based simulations concluded that the impact of GERD status on overall Zastaprazan exposure was not clinically meaningful.[3] This implies that dose adjustments based solely on the presence of GERD are unlikely to be necessary.

C. Absorption, Onset, and Duration of Action

Zastaprazan is characterized by a rapid onset of pharmacological action. Significant gastric acid suppression is typically observed within one hour of oral administration.[5] This rapid effect is consistent with its direct P-CAB mechanism. Furthermore, Zastaprazan provides sustained acid control, maintaining intragastric pH levels above 4 for approximately 85% of a 24-hour dosing interval.[15] This prolonged duration of action supports its efficacy with once-daily dosing and contributes to consistent symptom relief, including potential benefits for nocturnal acid reflux symptoms.

IV. Clinical Development and Efficacy

Zastaprazan has undergone rigorous clinical development, primarily focusing on its efficacy in treating common acid-related disorders. Key Phase 3 trials have established its therapeutic profile against standard-of-care PPIs.

A. Erosive Esophagitis (GERD)

The efficacy of Zastaprazan in erosive esophagitis (EE), a common manifestation of GERD, was evaluated in a large-scale Phase 3 clinical trial.

• Phase 3 Trial (NCT05443984 / ZERO-1) - Zastaprazan vs. Esomeprazole: This pivotal, multicenter, randomized, double-blind, active-controlled, non-inferiority study enrolled 300 adult patients with endoscopically confirmed EE. Participants were randomized to receive either Zastaprazan 20 mg once daily or the standard PPI Esomeprazole 40 mg once daily for a treatment duration of up to 8 weeks.[1] The primary efficacy endpoint was the cumulative EE healing rate at week 8, confirmed by endoscopy. Secondary endpoints included the healing rate at week 4, symptom response (assessed by the Reflux Disease Questionnaire - RDQ, and GERD Health-Related Quality of Life - GERD-HRQL scores), and safety.

Table 2: Comparative Efficacy of Zastaprazan in Phase 3 Erosive Esophagitis Trial (NCT05443984 / ZERO-1)

Endpoint	Zastaprazan 20mg (n=144 FAS)	Esomeprazole 40mg (n=138 FAS)	Difference (95% CI) / p-value	Reference(s)
Cumulative Healing Rate at Week 8	97.92% (141/144)	94.93% (131/138)	2.99% (-1.63% to 7.61%)*	9
			p=0.178 (Non-inferiority met)
Healing Rate at Week 4	95.14% (137/144)	87.68% (121/138)	p=0.026 (Superiority)	9
Symptom Response (RDQ, GERD-HRQL)	Significant improvement	Significant improvement	No significant difference	9

*FAS = Full Analysis Set. Difference calculated as Zastaprazan - Esomeprazole.

The results demonstrated that Zastaprazan 20 mg was non-inferior to Esomeprazole 40 mg for EE healing at week 8. A key finding was the statistically significantly higher healing rate observed with Zastaprazan at the earlier time point of week 4.[9] This earlier healing is a clinically relevant advantage, as faster mucosal repair can lead to quicker symptom alleviation and improved patient well-being. While overall symptom scores (RDQ, GERD-HRQL) showed comparable significant improvements in both groups over 8 weeks, the faster healing with Zastaprazan might underpin a more rapid initial symptomatic benefit, a factor that could drive physician and patient preference in clinical practice. In a subgroup of patients with more severe baseline EE (Los Angeles grades B, C, or D), there was some indication of a greater healing benefit with Zastaprazan, though this observation requires confirmation in larger cohorts due to limited sample size.[9]

• Phase 2 Trial (NCT04282954) in Erosive GERD: This earlier trial was completed and provided the necessary safety and efficacy data to support the progression of Zastaprazan into the larger Phase 3 program.[12]

B. Gastric Ulcers

Zastaprazan's efficacy in the treatment of gastric ulcers was investigated in another significant Phase 3 trial.

• Phase 3 Trial (NCT05448001) - Zastaprazan vs. Lansoprazole (DDW 2025 Presentation): This multicenter, randomized, double-blind, active-controlled, parallel-group Phase 3 study involved 328 patients with endoscopically confirmed gastric ulcers. Patients were randomized to receive either Zastaprazan 20 mg once daily or the standard PPI Lansoprazole 30 mg once daily for up to 8 weeks.[1] The primary endpoint was the cumulative healing rate of gastric ulcers at week 8, with the healing rate at week 4 and quality of life measures as secondary endpoints.

Table 3: Comparative Efficacy of Zastaprazan in Phase 3 Gastric Ulcer Trial (NCT05448001)

Endpoint	Zastaprazan 20mg	Lansoprazole 30mg	Notes	Reference(s)
Cumulative Healing Rate at Week 8 (PPS)	100.00%	97.06%	Non-inferiority demonstrated	11
Healing Rate at Week 4	94%	92%	Comparable	11
Quality of Life (Anxiety/Depression)	Improved	Improved	Zastaprazan showed statistically significant improvement at week 4	11

*PPS = Per Protocol Set.

The trial successfully demonstrated that Zastaprazan 20 mg was non-inferior to Lansoprazole 30 mg in the cumulative healing of gastric ulcers at week 8, with an impressive 100% healing rate in the Zastaprazan per-protocol set.[11] While Lansoprazole also showed high efficacy, achieving complete healing in all treated patients (per-protocol) with Zastaprazan underscores its robust therapeutic effect. The healing rates at week 4 were comparable between the two groups. An interesting secondary finding was the statistically significant improvement in anxiety/depression-related quality of life measures at week 4 with Zastaprazan.[11] This could suggest broader benefits beyond direct ulcer healing, possibly stemming from more consistent or rapid symptom control, although further investigation into this specific QoL aspect would be needed.

C. Investigational Indications

Onconic Therapeutics is actively exploring additional indications for Zastaprazan, aiming to broaden its therapeutic applications.

• Prevention of NSAID-Induced Peptic Ulcers: A Phase 3 clinical trial (NCT06439563) is planned or currently underway in South Korea to evaluate the efficacy and safety of Zastaprazan, administered as a capsule formulation, for the prevention of peptic ulcers induced by non-steroidal anti-inflammatory drugs (NSAIDs).[1] This is a clinically significant area, as NSAID-induced gastropathy is a common and potentially serious complication for chronic NSAID users. The rapid and sustained acid suppression characteristic of P-CABs like Zastaprazan might offer robust gastroprotection, potentially with advantages in consistency over PPIs, which often require specific timing relative to meals for optimal effect.
• Potential for Helicobacter pylori Eradication: Evidence of interest in this area comes from a patent application (WO/2025/116549) titled "Composition for Eradicating Helicobacter Pylori Comprising Zastaprazan or Pharmaceutically Acceptable Salt Thereof".[29] While no specific clinical trial data for Zastaprazan in H. pylori eradication were available in the provided information, this patent filing indicates active research and development. Successful H. pylori eradication typically requires combination therapy with antibiotics. The more potent and sustained acid suppression achieved by P-CABs could theoretically enhance the stability and efficacy of certain antibiotics (e.g., amoxicillin, clarithromycin) in the acidic gastric environment. This might lead to improved eradication rates, allow for shorter treatment durations, or prove effective against antibiotic-resistant H. pylori strains, addressing a growing challenge in current PPI-based regimens.
• Other Unspecified Gastrointestinal Disorders: Zastaprazan is also noted as being under development for other unspecified gastrointestinal disorders, suggesting a broader exploration of its utility in acid-related conditions.[4]

V. Safety and Tolerability

The safety and tolerability of Zastaprazan have been evaluated in its clinical development program, primarily through comparisons with established PPIs.

A. Overall Safety Profile from Clinical Trials

Across Phase 3 trials for erosive esophagitis (against Esomeprazole) and gastric ulcers (against Lansoprazole), Zastaprazan has demonstrated a generally well-tolerated safety profile.[9] The incidence and types of adverse events reported were largely comparable between Zastaprazan and the active PPI comparators.[9]

In the NCT05443984 trial for erosive esophagitis, treatment-emergent adverse events (TEAEs) were reported in 16% of patients in the Zastaprazan 20 mg group, compared to 22% in the Esomeprazole 40 mg group. Importantly, no serious adverse events or deaths were reported in either treatment arm during this study.[9] Similarly, in the gastric ulcer trial (NCT05448001), no unexpected safety issues were identified with Zastaprazan treatment.[11]

Table 4: Overview of Zastaprazan Safety Profile from Phase 3 Trials

Adverse Event Category	Zastaprazan 20mg (vs. Esomeprazole 40mg - EE Trial)	Zastaprazan 20mg (vs. Lansoprazole 30mg - GU Trial)	Reference(s)
Overall Incidence of TEAEs	16%	Comparable to Lansoprazole	9
Incidence of Serious AEs	0%	Comparable to Lansoprazole (no unexpected issues)	9
Discontinuation Rate due to AEs	Not specified, but no SAEs leading to death	Not specified, but no unexpected issues	9
Serum Gastrin Levels	Increased, then returned to baseline post-treatment	Not detailed	9

*EE = Erosive Esophagitis; GU = Gastric Ulcer; TEAEs = Treatment-Emergent Adverse Events. Data for GU trial often stated as "comparable" or "no unexpected issues" rather than specific percentages in snippets.

B. Impact on Serum Gastrin Levels

A known physiological response to potent gastric acid suppression is an increase in serum gastrin levels, due to the feedback mechanism involving gastric pH. In the erosive esophagitis trial, an increase in serum gastrin levels was observed during treatment with both Zastaprazan and Esomeprazole.[9] The magnitude of this increase showed a statistically significant difference between the two groups (p=0.047), with one report suggesting a "slightly greater extent in the zastaprazan group," although precise comparative figures for the extent of increase were not detailed.[9] A crucial observation was that serum gastrin levels returned to baseline levels for patients in both treatment groups within two weeks after discontinuation of the study medication.[9]

The transient increase in serum gastrin is an expected consequence of effective acid blockade. While the return to baseline post-treatment is reassuring for short-term therapy, the long-term implications of potentially higher or more sustained gastrin elevation during chronic P-CAB therapy compared to PPIs warrant continued investigation and post-marketing surveillance. This is a general point of attention for all potent acid-suppressing drugs due to theoretical concerns about trophic effects on enterochromaffin-like (ECL) cells, although the clinical significance of these effects in humans remains a subject of ongoing discussion and research. The degree and duration of hypergastrinemia with long-term Zastaprazan use will be important to monitor.

VI. Regulatory Status and Market Landscape

Zastaprazan has achieved regulatory approval in its domestic market and is actively being pursued for global market access through clinical development and strategic partnerships.

A. Approvals and Market Launch

• South Korea (Ministry of Food and Drug Safety - MFDS): Zastaprazan, under the brand name Jaqbo®, received its first regulatory approval from the South Korean MFDS on April 24/25, 2024. It was approved for the treatment of erosive gastroesophageal reflux disease (GERD) in adults.[1] This approval marked Jaqbo® as Korea's 37th domestically developed new drug.[18] Following its approval, Jaqbo® was launched in the South Korean market in October 2024. Domestic sales and marketing are handled by Jeil Pharmaceutical, the parent company of Onconic Therapeutics.[5]

B. Ongoing and Planned Regulatory Submissions

• South Korea (MFDS): Building on its initial approval, Onconic Therapeutics submitted an application to the MFDS in January 2025 to expand Jaqbo's indication to include the treatment of gastric ulcers. This submission was based on positive Phase 3 clinical trial results. Approval for this additional indication is anticipated in the first half of 2025.[18]
• China (National Medical Products Administration - NMPA): Zastaprazan is under development in China through a licensing agreement with Livzon Pharmaceutical Group. Livzon is responsible for the clinical development, regulatory approval, manufacturing, and commercialization in Greater China. Phase 3 clinical trials for erosive esophagitis and gastric ulcers are currently ongoing in this territory.[10]
• USA (Food and Drug Administration - FDA): Onconic Therapeutics is actively preparing documentation for a market approval submission to the US FDA.[23] Zastaprazan is listed in the FDA's Global Ingredient Archival System (GInAS).[31] As of early 2025, no US Drug Master File (US-DMF), FDA National Drug Code (NDC), or Abbreviated New Drug Application (ANDA) filings were noted for Zastaprazan.[32] Several clinical trials involving Zastaprazan have US sites registered, including NCT05448001 (Gastric Ulcer), NCT05443984 (Erosive Esophagitis), and a Phase 1 study for Ulcer/Helicobacter-associated gastritis.[15]
• Europe (European Medicines Agency - EMA): The term "Zastaprazan citrate" is registered in the European Union Telematics Controlled Terms (EUTCT) system, which is a controlled vocabulary used for regulatory submissions.[24] However, there was no information in the provided materials regarding active marketing authorization applications or approvals in the EU. No EU-API registration or Certificate of Suitability to the monographs of the European Pharmacopoeia (CEP/COS) was noted as of early 2025.[32]

C. Licensing Agreements and Partnerships

Onconic Therapeutics has pursued a strategy of out-licensing Zastaprazan to established pharmaceutical partners in key international markets:

• Livzon Pharmaceutical Group (China): In March 2023, Onconic Therapeutics granted exclusive rights to Livzon Pharmaceutical Group for the development, approval, manufacturing, and commercialization of Zastaprazan in Greater China (Mainland China, Taiwan, Hong Kong, and Macau). This significant deal is valued at $127.5 million, which includes a $15 million upfront payment and potential milestone payments up to $112.5 million, in addition to royalties on future sales. Onconic Therapeutics reported receiving a milestone payment from Livzon in March 2025, indicating progress in the collaboration.[10]
• Nordic Countries: In May 2025, Onconic Therapeutics signed a supply agreement with an unnamed Swedish pharmaceutical company. This agreement covers the distribution and sale of Jaqbo® in five Nordic countries, further expanding its European footprint.[19]
• Global Reach: As of May 2025, Onconic Therapeutics has reported technology transfer or export agreements for Jaqbo® in a total of 26 countries, demonstrating a broad international commercialization effort.[19] The rapid succession of regulatory approval in its home market, immediate pursuit of indication expansion, and the establishment of significant licensing deals in major markets like China and regions like the Nordics within a year of initial approval underscores an aggressive and confident global commercialization strategy for Zastaprazan. This proactive approach suggests a strong belief by Onconic and its partners in the drug's competitive profile and substantial market potential.

D. Commercial Performance and Market Outlook

• Jaqbo® Sales in South Korea: The early commercial performance of Jaqbo® in South Korea has been strong:
• Prescription sales reached 3.3 billion won in the fourth quarter of 2024 and further increased to 6.7 billion won in the first quarter of 2025.[34]
• Within the first six months of its launch, cumulative prescriptions for Jaqbo® amounted to 10 billion won.[34]
• Reflecting this strong uptake, Onconic Therapeutics reported total revenue of 14.8 billion won in 2024. The cumulative sales of Jaqbo®, likely encompassing licensing revenue and early sales, reached 35 billion won over a two-year period (presumably including pre-launch activities).[18]
• Buoyed by this initial success, Onconic raised its full-year revenue forecast by 54% to 24.9 billion won.[34]
• Competitive Landscape in South Korea: The South Korean market for P-CABs is becoming increasingly competitive. Jaqbo® was the third P-CAB to receive approval, following HK inno.N's K-CAB® (tegoprazan) and Daewoong Pharmaceutical's Fexuclue® (fexuprazan). Additionally, Daewon Pharmaceutical's P-CAB candidate, DW4421 (padoprazan), is advancing into Phase 3 trials, signaling further competition.[6] The robust early sales of Jaqbo®, despite being the third P-CAB to market, suggest that it is successfully differentiating itself or that the overall P-CAB market in South Korea is expanding rapidly enough to accommodate multiple new entrants. Its continued success will likely depend on ongoing clinical differentiation, physician adoption driven by perceived benefits (such as rapid healing or CYP2C19 independence), and potentially its pricing strategy relative to other P-CABs and established PPIs.

Table 5: Zastaprazan Regulatory and Commercialization Snapshot

Region/Country	Regulatory Body	Status	Key Partner(s)	Commercial Notes	Reference(s)
South Korea	MFDS	Approved (Erosive GERD, Apr 2024); Launched (Oct 2024); Gastric Ulcer indication submitted (Jan 2025)	Jeil Pharmaceutical	Strong initial sales (10B won in 6 months); Brand: Jaqbo®	1
China	NMPA	Phase 3 trials ongoing (EE, Gastric Ulcers)	Livzon Pharmaceutical Group	$127.5M licensing deal (Mar 2023)	10
USA	FDA	Preparing for market approval submission; Listed in GInAS; 3 US clinical trials registered	Onconic Therapeutics	No US-DMF, NDC, or ANDA noted yet	15
Europe	EMA	"Zastaprazan citrate" registered in EUTCT; No active MAA or approval noted			24
Nordic Countries	N/A	Distribution agreement signed (May 2025)	Unnamed Swedish company	Covers 5 Nordic countries	19
Global	N/A	Technology transfer/export agreements in 26 countries	Various		19

VII. Chemical and Pharmaceutical Details

A. Chemical Structure and Nomenclature

Zastaprazan is a synthetic organic compound. Its precise chemical structure is defined by its International Union of Pure and Applied Chemistry (IUPAC) name: azetidin-1-yl-[(2,6-dimethylphenyl)methylamino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl]methanone.[2] Structurally, it incorporates several heterocyclic moieties, including azetidine, imidazole (specifically an imidazo[1,2-a]pyridine core), and pyridine rings, along with a substituted phenylamine group.[1]

B. Physicochemical Properties

Key physicochemical properties of Zastaprazan, which are important for its drug-like characteristics and formulation, include [1]:

• Molecular Formula: C22H26N4O
• Molecular Weight: 362.47 g/mol
• Hydrogen Bond Acceptors: 5
• Hydrogen Bond Donors: 1
• Rotatable Bonds: 5
• Topological Polar Surface Area (TPSA): 47.94 Ų (This value suggests good potential for oral absorption and membrane permeability).
• XLogP3 (Logarithm of the octanol-water partition coefficient): 2.92 (This indicates a moderate lipophilicity, often favorable for oral drug absorption and distribution).
• Lipinski's Rule of Five Compliance: Zastaprazan adheres to Lipinski's Rule of Five (0 violations reported), which is an empirical rule to evaluate druglikeness and predict if a chemical compound with a certain pharmacological or biological activity has properties that would make it a likely orally active drug in humans.

C. Formulations and Dosage

• Marketed Formulation (Jaqbo®): In South Korea, Zastaprazan (as zastaprazan citrate) is marketed as film-coated tablets for oral administration.[4]
• Clinical Trial Dosage: The dose consistently evaluated and found effective in Phase 3 trials for both erosive esophagitis and gastric ulcers is 20 mg administered once daily.[9]
• Investigational Formulation: For the planned Phase 3 trial (NCT06439563) investigating the prevention of NSAID-induced peptic ulcers, a capsule formulation of Zastaprazan is intended to be used.[14]

D. Patent Information

Zastaprazan is protected by several patents, reflecting its novelty and ongoing development:

• WO2018008929: This international patent application likely covers the Zastaprazan compound itself or its primary use as a proton pump inhibitor (more accurately, a P-CAB).[13]
• KR1777971: A Korean patent, likely related to the compound or its use in South Korea.[13]
• WO/2025/116549: This recent international patent application specifically claims a "Composition for Eradicating Helicobacter Pylori Comprising Zastaprazan or Pharmaceutically Acceptable Salt Thereof".[29] The patent strategy, particularly the recent application for H. pylori eradication, illustrates a clear approach towards lifecycle management and indication expansion for Zastaprazan. By securing intellectual property for new uses and compositions, Onconic Therapeutics aims to broaden the drug's therapeutic utility and extend its market exclusivity, which is a common and important strategy in the pharmaceutical industry, especially as the P-CAB field becomes more competitive.

VIII. Summary and Future Perspectives

A. Recapitulation of Zastaprazan's Profile

Zastaprazan (Jaqbo®) has emerged as a novel, orally administered potassium-competitive acid blocker (P-CAB) from Onconic Therapeutics. Clinical evidence from Phase 3 trials has established its non-inferiority to standard PPIs (esomeprazole and lansoprazole) in the healing of erosive esophagitis and gastric ulcers, respectively. Notably, Zastaprazan demonstrated a statistically significant advantage in achieving faster healing rates at 4 weeks in patients with erosive esophagitis.[9] Its pharmacokinetic profile is distinguished by a rapid onset of action, sustained acid suppression over 24 hours, the convenience of food-independent dosing, and, crucially, a lack of significant influence from CYP2C19 genetic polymorphisms, which can affect the metabolism of many PPIs.[3] The safety and tolerability profile of Zastaprazan appears generally comparable to that of PPIs, with a transient elevation of serum gastrin levels being a monitored class effect of potent acid suppressants.[9]

B. Potential Advantages and Place in Therapy for Acid-Related Disorders

The key pharmacological advantages of Zastaprazan—rapid and sustained acid control, dosing flexibility (food-independence), and predictable metabolism (CYP2C19 independence)—position it as a strong therapeutic alternative to traditional PPIs. These attributes may be particularly beneficial for patients seeking prompt symptom relief, individuals with variable meal schedules making pre-meal PPI dosing challenging, or those with known CYP2C19 genetic variants that could compromise PPI efficacy. Consequently, Zastaprazan has the potential to become a preferred agent for the initial treatment of moderate to severe erosive esophagitis and gastric ulcers, and may also find a significant role in the long-term management of GERD.

The advent of Zastaprazan and other P-CABs signals a potential evolution in the standard of care for certain acid-related disorders. The distinct pharmacological profile offers tangible benefits over older PPIs. As more long-term safety data and comparative effectiveness evidence, including health economic analyses, become available, P-CABs like Zastaprazan are likely to be increasingly incorporated into clinical guidelines, possibly as first-line therapeutic options in specific patient populations or for particular clinical scenarios where their unique advantages are most pronounced.

C. Ongoing Research and Future Development Directions

The development of Zastaprazan is actively continuing with programs aimed at expanding its therapeutic indications. A Phase 3 trial (NCT06439563) is investigating its utility in the prevention of NSAID-induced peptic ulcers, and patent filings (WO/2025/116549) suggest exploration of its role in Helicobacter pylori eradication regimens.[1]

Global market expansion remains a clear strategic priority for Onconic Therapeutics, evidenced by ongoing Phase 3 trials in China under partnership with Livzon Pharmaceutical Group, and regulatory preparations for other major markets, including the USA.[10]

As with any new class of potent acid-suppressing agents, long-term safety, particularly concerning the effects of sustained and profound acid suppression on gastrin levels and other physiological parameters, will be an important area for post-marketing surveillance and continued research. This applies not only to Zastaprazan but to the P-CAB class as a whole.

The clinical and commercial journey of Zastaprazan will significantly contribute to the broader understanding and establishment of the P-CAB class. Its performance in various indications, through different regulatory pathways, and across diverse patient populations worldwide will provide valuable real-world evidence. These data will help to refine the therapeutic positioning of P-CABs, clarify their benefits and risks relative to PPIs and each other, and ultimately shape how this evolving class of drugs is integrated into global gastroenterology practice.

Works cited

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