RegulationOrphan Drug (United States), Orphan Drug (South Korea), Overseas New Drugs Urgently Needed in Clinical Settings (China), Fast Track (United States)

Structure/Sequence

Molecular FormulaC59H89N19O13S.C2H4O2

InChIKeyHKMZRZUEADSZDQ-DZJWSCHMSA-N

CAS Registry138614-30-9

Sequence Code 14375414

Clinical Trials associated with Icatibant Acetate

CTIS2025-521354-42-00

/ Not yet recruitingPhase 2IIT

A randomized, double-blind crossover study to investigate the analgesic efficacy of the bradykinin (B2) antagonist icatibant for propofol injection pain in healthy adult participants.

Start Date01 Sep 2025

Sponsor / Collaborator-

NCT07290855

/ CompletedPhase 4

A Phase IV Clinical Study of Evaluating the Safety and Efficacy of Icatibant Injection (Icanticure) in the Treatment of Patients With Bradykinin Induced Angioedema

This is a phase IV clinical study. The investigators collect patients with a diagnosis of bradykinin induced angioedema. For a specific study period and prospectively arrange, the eligible patients who has an acute attack of angioedema could be treated by icatibant Injection (Icanticure®).
The drug, icatibant injection has been reimbursed by National Health Insurance Agency, Taiwan (NHI) in the treatment of diagnosed patients with hereditary angioedema. However, the reimbursement is still limited for some patients with atypical conditions. Therefore, Nang Kuang Company initiates a phase IV case collection study and supplies Icanticure® for free during the study period. Patients who still unable to obtain NHI's reimbursed icatibant drug is eligible for the inclusion, enter into the study and can be treated by Icanticure® to meet their clinical urgent needs. The safety and efficacy of Icanticure® are evaluated by the prospective, planed assessments in the enrolled patients.

Start Date27 Sep 2024

Sponsor / Collaborator

Nang Kuang Pharmaceutical Co., Ltd.

CTR20241595

/ CompletedPhase 4

拉那利尤单抗（达泽优）和艾替班特（飞泽优®）在遗传性血管性水肿患者中的真实世界疗效和安全性：一项中国观察性研究

[Translation] Real-world efficacy and safety of lanariumab (DaZeYu) and icatibant (FazeYu®) in patients with hereditary angioedema: an observational study in China

在真实世界的临床实践中接受至少一剂拉那利尤单抗或艾替班特的中国患者中，评价拉那利尤单抗和艾替班特的疗效和安全性。

[Translation]

To evaluate the efficacy and safety of lanariumab and icatibant in Chinese patients who received at least one dose of lanariumab or icatibant in real-world clinical practice.

Start Date20 Jul 2024

Sponsor / Collaborator

Dhl Supply Chain Netherlands BV

[+3]

100 Clinical Results associated with Icatibant Acetate

100 Translational Medicine associated with Icatibant Acetate

100 Patents (Medical) associated with Icatibant Acetate

1,609

Literatures (Medical) associated with Icatibant Acetate

01 Jun 2026·IMMUNOLOGY LETTERS

Compartment-specific activation of kinin B1 and B2 receptors drives the production of vasoactive and inflammatory mediators during SARS-CoV-2 infection

Article

Author: Mello, Carlos Fernando ; de Oliveira, Sara Marchesan ; Grotto, Fabielly Scolari ; Ulrich, Henning ; Bernasconi, Thissiane de Lima Gonçalves ; Wilot, Leandre Carmem ; Viero, Fernanda Tibolla ; Bizarro, Cristiano Valim ; Pillat, Micheli Mainardi ; Librelotto, Daniele Rubert Nogueira ; de Souza, Julia Brandt ; Brusco, Indiara ; Basso, Luiz Augusto ; Kodavara, Elyan ; Decker, Eduardo Reichert ; Sperotto, Nathalia Denise de Moura ; Silveira, Maiele Dornelles ; Vidal, Taís ; de Lara, Jéssica Dotto ; Glaser, Talita ; Weber, Andressa de Azambuja Pias ; Bortoluzzi, Luisa Donato ; Santini Dos Santos, Ana Paula

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) disrupts multiple host regulatory systems, including the kallikrein-kinin system (KKS), which plays a central role in vascular homeostasis and inflammation. Following viral entry, angiotensin-converting enzyme 2 (ACE2) is internalized and inactivated, impairing the degradation of des-Arg⁹-bradykinin (DABK), a selective agonist of the inducible kinin B1 receptor (B1R), while inflammatory feedback mechanisms may further elevate bradykinin (BK), the kinin B2 receptor (B2R) agonist. It has been postulated that the kinin storm observed in COVID-19 patients may lead to pulmonary angioedema, promote the exacerbated production of pro-inflammatory cytokines, and be related to disease progression, permanent sequelae, and death. However, it remains unknown whether in vitro SARS-CoV-2 infection triggers alterations in the KKS and its downstream inflammatory and vasoactive mediators. Here, we investigated how SARS-CoV-2 infection modulates kinin signaling and its downstream inflammatory and vasoactive mediators in Vero E6 and human endothelial (HUVEC) cells. SARS-CoV-2 infection increased BK levels and markedly upregulated B1R gene expression in Vero E6 cells (up to 20-fold), while B2R expression remained unchanged. Both BK and DABK reduced ACE2 expression in Vero E6 cells, an effect most likely mediated by DABK-B1R signaling due to the minimal expression of B2R in this cell line. Viral infection induced robust production of nitric oxide (NO) and interleukin-6 (IL-6) in Vero E6 cells, and supernatants from infected cells triggered similar responses in HUVECs. Pharmacological blockade of B1R with R-715 selectively prevented SARS-CoV-2-induced NO production in Vero E6 cells, whereas IL-6 induction occurred through B1R-independent mechanisms. In contrast, in endothelial HUVEC cells exposed to serum from patients with severe COVID-19, B2R antagonism with HOE-140 prevented both NO and IL-6 production, suggesting a key role for B2R in both vascular cytokine amplification and vasoactive mediator production. Our findings reveal a compartment-specific and complementary activation of B1R and B2R during SARS-CoV-2 infection, establishing the KKS as a key mediator of endothelial alterations and inflammatory amplification in COVID-19 and positioning B1R and B2R as therapeutic targets.

01 Feb 2026·THERAPIE

Angioedema reported with tissue plasminogen activators: A need to communicate on bradykinin- and histamine-mediated mechanisms

Article

Author: Polard, Elisabeth ; Gautier, Sophie ; Largeau, Bérenger ; Beau-Salinas, Frédérique ; Maurier, Anaïs ; Jonville-Bera, Annie-Pierre

AIM OF THE STUDY:

Angioedema (AE) is a potentially life-threatening adverse effect. The mechanism can be either bradykinin- (BK-AE) or histamine-mediated (Hi-AE), each requiring different management. AE are reported with recombinant tissue plasminogen activators (alteplase and tenecteplase), for which an immunoallergic or bradykinic mechanism is suggested. The aim of this study was to describe the characteristics of cases of AE (BK or Hi) reported with rt-PA to the French Regional Pharmacovigilance Centers in order to optimize their identification and management.

METHODS:

All cases of AE reported with alteplase or tenecteplase until 30 November, 2023 were analyzed and classified as Hi-AE or BK-AE using the clinical manifestations, the management and the allergological workup.

RESULTS:

We analyzed 151 cases of AE, with a median time to onset of 1h (IQR=1-2h), all localized at the head. From them, 150 were with alteplase use for acute ischemic stroke (98%) or myocardial infarction (2%), and 1 with tenecteplase. Of them 107 (71%) could be clearly categorized and were classified as 98 (92%) cases of BK-AE and 9 (8%) cases of Hi-AE. When the use of icatibant or C1 esterase inhibitor is specified, it was the 1st-line treatment for 32/47 (68%) patients.

CONCLUSION:

The majority of cases of AE reported with rt-PA, are BK-AE involving alteplase. This is consistent with the effects of rt-PA, which activates the kinin pathway by hydrolyzing plasminogen to plasmin, resulting in the formation of bradykinin. Clinicians need to be informed of this mechanism, in order to early prescribe the appropriate treatment, as we detect that it was not systematically used as 1st-line therapy for a lot of cases.

01 Feb 2026·World Allergy Organization Journal

Clinical features of hereditary angioedema involving the gastrointestinal tract: A retrospective analysis

Article

Author: Zheng, Danping ; Ma, Haiyuan ; Huang, Zhoulin ; Chen, Baili ; Xiong, Shanshan ; Mao, Ren ; Wang, Yangdi ; Tian, Chunyang ; Li, Xuehua ; Ke, Yangyang ; He, Yao ; Chen, Minhu

Background:

Hereditary angioedema (HAE) is a rare, severe, disabling, and life-threatening disorder characterized by recurrent and unpredictable edema of skin and mucous membranes. Gastrointestinal edema, often presenting as abdominal pain, is common but frequently misdiagnosed, leading to unnecessary surgeries. This study aims to characterize gastrointestinal edema in HAE patients to improve early diagnosis and guide treatment.

Method:

We analyzed 61 patients with HAE who were admitted in our hospital between April 1, 2023 and August 31, 2025. Data on demographic characteristics, clinical manifestations, laboratory findings, imaging results, and treatment outcomes were collected through questionnaires and hospital electronic records.

Result:

Among the patients, 86.9% experienced gastrointestinal edema, mostly characterized by abdominal pain (94.3%), nausea (79.2%), and diarrhea (71.7%). Misdiagnosis occurred in 73.6% of cases, and 22.6% underwent unnecessary surgeries. The median age of gastrointestinal edema onset was 16.0 years, with the most severe episodes occurring at a median age of 25.0 years. The median annual frequency of attacks was 4.0/year, with a median severity score of 7.0. Acute attacks showed elevated D-dimer, white blood cells, neutrophils, and hemoglobin. CT imaging frequently revealed intestinal wall thickening and abdominal-pelvic effusion. Lanadelumab demonstrated superior efficacy over danazol in reducing both the frequency and severity of edema attacks, while icatibant significantly shortened the duration of edema episodes.

Conclusion:

This study updates the clinical and imaging features of gastrointestinal edema in Chinese patients with HAE, identifies biomarkers of gastrointestinal edema attacks, and highlights the efficacy of lanadelumab and icatibant, aiding timely diagnosis and treatment.

News (Medical) associated with Icatibant Acetate

20 Mar 2026

·www.biospace.com

Evidence of Efficacy and Safety of Deucrictibant for Prophylaxis and On-Demand Treatment of Hereditary Angioedema Attacks Published Back-to-Back in The Lancet Haematology

Results from Phase 2 clinical studies, CHAPTER-1 and RAPIDe-1, provide evidence of viability of bradykinin B2 receptor antagonism in management of HAE ZUG, Switzerland, March 20, 2026 (GLOBE NEWSWIRE) -- Pharvaris (Nasdaq: PHVS), a late-stage biopharmaceutical company developing novel, oral bradykinin B2 receptor antagonists to help address unmet needs of those living with bradykinin-mediated diseases such as hereditary angioedema (HAE) and acquired angioedema due to C1 inhibitor deficiency (AAE-C1INH), today announced that two articles have been published back-to-back in the same issue of The Lancet Haematology. The articles detail data from the two randomized Phase 2 studies, CHAPTER-1 and RAPIDe-1 , evaluating the efficacy and safety of deucrictibant, a potent, orally bioavailable small-molecule bradykinin B2 receptor antagonist, in development for the prophylaxis and on-demand treatment of HAE attacks, respectively. “Since HAE is a bradykinin-mediated disease, regulation of bradykinin signaling through B2 receptor antagonism could both prevent HAE attacks and manage angioedema symptoms when they occur,” said Marc A. Riedl, M.D., M.S., Professor of Medicine, Clinical Director of the U.S. Hereditary Angioedema Association (HAEA) Angioedema Center at the University of California San Diego (UCSD), and investigator in both studies. “The statistically significant, placebo-controlled data from these two distinct clinical studies provide important evidence that deucrictibant, a bradykinin B2 receptor antagonist, may offer a viable option for both prophylactic and acute treatment of HAE attacks. Based on these results, deucrictibant is emerging as a potentially unique oral therapy for HAE, providing on-demand and preventative treatment effects through the availability of both the immediate-release capsule and extended-release tablet. This complementary approach may further improve HAE management for patients and prescribers alike.” CHAPTER-1 Study Results CHAPTER-1, a double-blind, placebo-controlled Phase 2 proof-of-concept study of deucrictibant for the prophylactic treatment of HAE attacks, demonstrated statistically significant reduction in the occurrence of attacks and clinically meaningful improvements in disease control and health-related quality of life. Deucrictibant was well tolerated at both doses tested. RAPIDe-1 Study Results RAPIDe-1, a double-blind, placebo-controlled Phase 2 study of deucrictibant immediate-release capsule for the on-demand treatment of HAE attacks, demonstrated a statistically significant reduction in severity of attack manifestations, as well as a reduced time to symptom relief and resolution. Deucrictibant was well tolerated at all doses tested. Peng Lu, M.D., Ph.D., Chief Medical Officer of Pharvaris, stated, “icatibant use has established bradykinin B2 receptor antagonism as the standard-of-care approach for on-demand treatment of HAE attacks. The RAPIDe-1 data are the first-ever clinical study data supporting deucrictibant as an oral on-demand therapy, and the CHAPTER-1 data are the first-ever clinical study data supporting bradykinin B2 receptor antagonism as an effective approach for prophylaxis of HAE attacks. Upon regulatory approval for both indications, deucrictibant could offer an end-to-end portfolio of options for bradykinin-mediated angioedema care. The two articles, published concurrently in The Lancet Haematology , add to the scientific evidence to further advance understanding of bradykinin-mediated angioedema and eventually inform clinical decisions about management in real-world clinical practice.” Topline data from CHAPTER-3 ( NCT06669754 ), an ongoing Phase 3 clinical study evaluating deucrictibant extended-release tablet for the prophylactic treatment of HAE attacks, is anticipated in the third quarter of 2026. Topline data from RAPIDe-3 ( NCT06343779 ), a pivotal, placebo-controlled Phase 3 clinical study evaluating deucrictibant immediate-release capsule for the on-demand treatment of HAE attacks, demonstrated that treatment with deucrictibant resulted in faster symptom relief and complete symptom resolution of HAE attacks and in most attacks being treated with a single capsule. These confirmatory data of deucrictibant’s potential as an oral on-demand treatment were presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) 2026 Annual Meeting . The full articles can be found here: Oral deucrictibant for prophylaxis of hereditary angioedema attacks (CHAPTER-1): primary analysis of a randomised, double-blind, placebo-controlled, phase 2 trial Oral deucrictibant for on-demand treatment of hereditary angioedema attacks (RAPIDe-1): a randomised, double-blind, placebo-controlled, phase 2 trial About Deucrictibant Deucrictibant is a novel, potent, orally bioavailable small-molecule bradykinin B2 receptor antagonist currently in clinical development. Deucrictibant is being investigated for its potential to prevent the occurrence of bradykinin-mediated angioedema attacks and to treat the manifestations of attacks if/when they occur by inhibiting bradykinin signaling through the bradykinin B2 receptor. Pharvaris is developing two formulations of deucrictibant for oral administration: an extended-release tablet to enable sustained absorption and efficacy as prophylactic treatment, and an immediate-release capsule to enable rapid onset of activity for on-demand treatment. Deucrictibant has been granted orphan drug designation for the treatment of bradykinin-mediated angioedema by the U.S. Food and Drug Administration, the European Commission, and Swissmedic. About Pharvaris Pharvaris is a late-stage biopharmaceutical company developing novel, oral bradykinin B2 receptor antagonists to help address unmet needs in bradykinin-mediated conditions, including all types of bradykinin-mediated angioedema. Pharvaris’ aspiration is to offer therapies with injectable-like efficacy™, a well-tolerated profile, and the convenience of oral administration to prevent and treat bradykinin-mediated angioedema attacks. By delivering on this aspiration, Pharvaris aims to provide a new standard of care in bradykinin-mediated angioedema. Pharvaris is preparing marketing authorization applications for deucrictibant immediate-release capsule as an on-demand treatment of HAE attacks, and a global pivotal Phase 3 study of deucrictibant extended-release tablet for the prevention of HAE attacks (CHAPTER-3) is ongoing with topline data anticipated in the third quarter of 2026. In addition, CREAATE is an ongoing Phase 3 study of deucrictibant for the prophylactic and on-demand treatment of AAE-C1INH attacks. For more information, visit . Forward Looking Statements This press release contains certain forward-looking statements that involve substantial risks and uncertainties. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including, without limitation, statements relating to our future plans, studies and trials, and any statements containing the words “believe,” “anticipate,” “expect,” “estimate,” “may,” “could,” “should,” “would,” “will,” “intend” and similar expressions. These forward-looking statements are based on management’s current expectations, are neither promises nor guarantees, and involve known and unknown risks, uncertainties and other important factors that may cause Pharvaris’ actual results, performance or achievements to be materially different from its expectations expressed or implied by the forward-looking statements. Such risks include but are not limited to the following: uncertainty in the outcome of our interactions with regulatory authorities, including the FDA; the expected timing, progress, or success of our clinical development programs, especially for deucrictibant immediate-release capsules and deucrictibant extended-release tablets, which are in late-stage global clinical trials; our ability to replicate the efficacy and safety demonstrated in the RAPIDe-1, RAPIDe-2, RAPIDe-3, and CHAPTER-1 Phase 2 and Phase 3 studies in ongoing and future nonclinical studies and clinical trials, such as CHAPTER-3, and CREAATE; the timing and outcome of regulatory approvals, including the timing and outcome of our planned submission of an NDA with the FDA in the first half of 2026 for the on-demand treatment of acute attacks of HAE; risks arising from epidemic diseases, which may adversely impact our business, nonclinical studies, and clinical trials; our ability to potentially use deucrictibant for alternative purposes, for example to treat C1-INH deficiency (AAE-C1INH); the value of our ordinary shares; the timing, costs and other limitations involved in obtaining regulatory approval for our product candidates, or any other product candidate that we may develop in the future; our ability to establish commercial capabilities or enter into agreements with third parties to market, sell, and distribute our product candidates; our ability to compete in the pharmaceutical industry, including with respect to existing therapies, emerging potentially competitive therapies and with competitive generic products; our ability to market, commercialize and achieve market acceptance for our product candidates; our ability to produce sufficient amounts of drug product candidates for commercialization; our ability to raise capital when needed and on acceptable terms; regulatory developments in the United States, the European Union and other jurisdictions; our ability to protect our intellectual property and know-how and operate our business without infringing the intellectual property rights or regulatory exclusivity of others; our ability to manage negative consequences from changes in applicable laws and regulations, including tax laws (including the Biosecure Act), our ability to maintain an effective system of internal control over financial reporting; changes and uncertainty in general market conditions; disruptions at the FDA and other agencies; changes and uncertainty in general market, political and economic conditions, including as a result of inflation and geopolitical conflicts; changes in regulations and customs, tariffs and trade barriers; and the other factors described under the headings “Cautionary Statement Regarding Forward-Looking Statements” and “Item 3. Key Information—D. Risk Factors” in our Annual Report on Form 20-F and other periodic filings with the U.S. Securities and Exchange Commission. These and other important factors could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. While Pharvaris may elect to update such forward-looking statements at some point in the future, Pharvaris disclaims any obligation to do so, even if subsequent events cause its views to change. These forward-looking statements should not be relied upon as representing Pharvaris’ views as of any date subsequent to the date of this press release. CONTACT: Contact Maggie Beller Executive Director, Head of Corporate and Investor Communications maggie.beller@pharvaris.com

Clinical ResultPhase 2Phase 3Orphan Drug

09 Mar 2026

·www.biospace.com

Septerna Highlights Pipeline Progress and Reports Fourth Quarter and Full Year 2025 Financial Results

Compelling Phase 1 Data for SEP-631 (MRGPRX2 NAM) in Healthy Volunteers Support Phase 2b Development, Initially in Chronic Spontaneous Urticaria (CSU) in Second Half of 2026 Advancing SEP-479 (PTH1R Agonist) Toward Phase 1 Initiation in First Half of 2026 Cash Runway Expected to Support Operating Plans at Least into 2029 SOUTH SAN FRANCISCO, Calif., March 09, 2026 (GLOBE NEWSWIRE) -- Septerna, Inc. (Nasdaq: SEPN), a clinical-stage biotechnology company pioneering a new era of G protein-coupled receptor (GPCR) drug discovery, today highlighted pipeline progress and anticipated milestones and reported financial results for the fourth quarter and full year ended December 31, 2025. "We made significant strides advancing our pipeline in the past year, and 2026 has already delivered a meaningful milestone with positive Phase 1 results for SEP-631,” said Jeffrey Finer, M.D., Ph.D., chief executive officer and co-founder of Septerna. “These results demonstrate clinical proof-of-mechanism and validate the ability of our Native Complex Platform ® to uncover novel mechanisms of action and rapidly generate differentiated oral small molecules for historically challenging GPCRs. With SEP-479 approaching Phase 1 initiation in the coming months, SEP-631 poised for Phase 2 development in the second half of the year, and additional programs progressing behind them, we believe 2026 will be a year of strong progress for Septerna and for the patients we are committed to serving.” Recent Pipeline Progress and Anticipated Milestones SEP-631 MRGPRX2 NAM for Mast Cell Diseases: In March 2026, Septerna presented positive results from its Phase 1 clinical trial evaluating SEP-631, its potent, selective and insurmountable oral small molecule MRGPRX2 negative allosteric modulator (NAM) and outlined its initial Phase 2 development strategy. Key findings include: Safety: SEP-631 was well-tolerated at all doses studied with an adverse event pro to placebo. Pharmacokinetics (PK): SEP-631 demonstrated a PK pro of convenient once-daily oral dosing without food restrictions. Pharmacodynamics (PD): SEP-631 produced robust suppression of wheal formation across evaluated dose levels, with complete inhibition observed at doses as low as 10 mg once daily following the 10 µg/mL icatibant challenge. Following the 100 µg/mL icatibant challenge, inhibition was dose-dependent, with progressively greater suppression observed at increasing SEP-631 doses with near to complete inhibition achieved at 90 and 200 mg once daily. Septerna plans to initiate a Phase 2b trial of SEP-631 in CSU in the second half of 2026 following completion of long-term toxicology studies, with an open-label study in chronic inducible urticaria (CIndU) patients with symptomatic dermatographism to follow. Septerna is also evaluating additional mast cell-driven diseases with high unmet need and MRGPRX2 expression on tissue-resident mast cells. SEP-479 PTH1R Agonist for Hypoparathyroidism: Septerna has completed IND-enabling studies for SEP-479, its potent and selective oral small molecule PTH1R agonist, and is on track to initiate a Phase 1 clinical trial in the first half of 2026. TSHR NAM Program: Septerna continues to progress toward development candidate selection for its TSHR NAM program, with the goal of delivering a potential disease-modifying oral treatment for Graves’ disease and thyroid eye disease. Discovery Programs: Septerna also continues to advance discovery-stage programs utilizing its Native Complex Platform ® across multiple therapeutic areas. Business Highlights In January 2026, Septerna appointed Mark A. Wilson as chief legal officer. Mr. Wilson is an accomplished pharmaceutical and biotech executive with more than 25 years of experience across intellectual property, corporate legal, strategic collaborations and corporate governance matters. Fourth Quarter and Full Year 2025 Financial Results Cash Position: Cash, cash equivalents, and marketable securities totaled $548.7 million as of December 31, 2025, compared to $420.8 million as of December 31, 2024. During 2025, Septerna received a $195.0 million upfront payment from Novo Nordisk and a $12.5 million milestone payment from Vertex. Septerna expects its existing cash runway to fund operations at least into 2029. Revenue: Revenue was $24.1 million for the fourth quarter of 2025 and $46.0 million for the full year ended December 31, 2025, compared to $0.2 million for the fourth quarter of 2024 and $1.1 million for the full year ended December 31, 2024. Revenue for the fourth quarter of 2025 included the amortization of $14.0 million of the $195.0 million upfront payment received from Novo Nordisk in July 2025, as well as $10.1 million for research services associated with the collaboration. Revenue for the full year ended December 31, 2025, included the amortization of $26.8 million of the $195.0 million upfront payment received from Novo Nordisk in July 2025, as well as $18.6 million for research services associated with the collaboration. R&D Expenses : Research and development (R&D) expenses were $31.9 million for the fourth quarter of 2025 and $97.6 million for the full year ended December 31, 2025, compared to $19.3 million for the fourth quarter of 2024 and $65.3 million for the full year ended December 31, 2024. G&A Expenses: General and administrative (G&A) expenses were $8.3 million for the fourth quarter of 2025 and $29.2 million for the full year ended December 31, 2025, compared to $5.6 million for the fourth quarter of 2024 and $16.6 million for the full year ended December 31, 2024. Net Loss: Net loss was $10.7 million for the fourth quarter of 2025 and $48.9 million for the full year ended December 31, 2025, compared to net losses of $20.7 million for the fourth quarter of 2024 and $71.8 million for the full year ended December 31, 2024. About Septerna Septerna, Inc. is a clinical-stage biotechnology company with a world-class team of GPCR experts and drug developers advancing cutting-edge science to unlock the full potential of GPCR therapies for patients with significant unmet needs. The company’s proprietary Native Complex Platform ® is designed to enable new approaches to GPCR drug discovery and has led to the development of a diverse pipeline of novel oral small molecule drug candidates. Septerna is advancing programs in endocrinology, immunology and inflammation, metabolic diseases and additional therapeutic areas, both independently and with partners. For more information, please visit . Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements about Septerna’s beliefs and expectations regarding: the continued advancement of SEP-631, including the plan to initiate a Phase 2b clinical study in CSU in the second half of 2026 subject to the successful completion of long-term preclinical toxicology studies; the role of MRGPRX2 in mast cell-driven diseases; the potential of SEP-631 to provide a convenient oral treatment option for patients with CSU and other mast cell-driven diseases; expectations regarding the anticipated once-daily dosing frequency of SEP-631; the ability of the SEP-631 Phase 1 safety and efficacy observations to successfully translate into clinical outcomes in patients; the continued advancement of SEP-479, including the plan to initiate a Phase 1 clinical study in the first half of 2026; the continued development of its TSHR NAM program; the advancement of its discovery-stage programs across multiple therapeutic areas; the potential of its proprietary Native Complex Platform ® ; the size and growth potential of the markets for its current and future product candidates; its expectations regarding strategic plans for its business, product candidates, and technology; its expectations regarding the company’s uses of capital, expenses and financial results, including its expected cash runway at least into 2029; and the scope of protection it is able to establish and maintain for intellectual property rights covering its Native Complex Platform ® and its product candidates. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “might,” “objective,” “ongoing,” “plan,” “predict,” “project,” “potential,” “should,” or “would,” or the negative of these terms, or other comparable terminology are intended to identify forward-looking statements, although not all forward looking statements contain these identifying words. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks associated with: Septerna’s product candidates successfully entering and advancing through clinical trials (including those for SEP-631) including uncertainties related to opening INDs and obtaining other regulatory approvals; risks related to clinical development outcomes including unexpected safety or efficacy findings; the results of preclinical studies including the long-term toxicology studies for SEP-631, or clinical studies not being predictive of future clinical outcomes; risks related to the timing of initiating clinical studies and future availability of clinical data; the scope of protection Septerna is able to establish and maintain for intellectual property rights covering its Native Complex Platform ® and its product candidates; and Septerna’s ability to identify and enter into future license agreements and collaborations; and general economic, industry and market conditions. These and other risks and uncertainties are described in greater detail in the section entitled “Risk Factors” in Septerna’s Annual Report on Form 10-K for the year ended December 31, 2025, as well as any subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent Septerna’s views only as of today and should not be relied upon as representing its views as of any subsequent date. Septerna explicitly disclaims any obligation to update any forward-looking statements subject to any obligations under applicable law. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Investor Contact: Renee Leck, THRUST renee@thrustsc.com Media Contact: Carly Scaduto, THRUST carly@thrustsc.com SEPTERNA, INC. Condensed Statements of Operations (In thousands, except for share and per share data) (Unaudited) Three Months Ended Years Ended December 31, 2025 2024 2025 2024 Revenue $ 24,118 $ 212 $ 45,951 $ 1,075 Operating expenses: Research and development 31,861 19,317 97,584 65,337 General and administrative 8,280 5,613 29,164 16,561 Gain on sale of non-financial asset — — (12,500 ) — Total operating expenses 40,141 24,930 114,248 81,898 Loss from operations (16,023 ) (24,718 ) (68,297 ) (80,823 ) Interest income and other expense, net 5,297 3,890 19,430 8,527 Provision (benefit) for income taxes 12 (160 ) 12 (498 ) Net loss $ (10,738 ) $ (20,668 ) $ (48,879 ) $ (71,798 ) Net loss per share, basic and diluted $ (0.24 ) $ (0.64 ) $ (1.10 ) $ (7.26 ) Weighted-average shares outstanding, basic and diluted 44,579,697 32,383,314 44,258,338 9,891,126 Condensed Balance Sheets (In thousands) (Unaudited) December 31, September 30, December 31, 2025 2025 2024 Cash, cash equivalents and marketable securities $ 548,658 $ 561,558 $ 420,789 Working capital (1) 324,033 416,399 343,975 Total assets 596,187 606,653 456,554 Total liabilities 214,261 217,922 36,507 Additional paid-in capital 548,517 544,826 538,321 Accumulated deficit (167,253 ) (156,515 ) (118,374 ) Total stockholders' equity $ 381,926 $ 388,731 $ 420,047 Working capital is defined as total current assets less total current liabilities. See our financial statements and the related notes thereto included in our Annual Report on Form 10-K for the year ended December 31, 2025, for further details regarding our current assets and current liabilities.

Phase 1Financial StatementExecutive ChangeClinical ResultPhase 2

01 Mar 2026

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Septerna Announces Positive Phase 1 Data for SEP-631, an Oral MRGPRX2 NAM for the Treatment of Mast Cell-Driven Diseases, and Outlines Initial Phase 2 Development Strategy

SEP-631 Demonstrated Robust, Dose-Dependent Inhibition of Icatibant-Induced Skin Wheal Formation, with Complete Inhibition Observed at Doses as Low as 10 mg Once-Daily Well-Tolerated Across All Doses Studied with an Adverse Event Profile Comparable to Placebo; Pharmacokinetic Profile Supports Once-Daily Oral Dosing Phase 2 Development Planned to Begin with Chronic Spontaneous Urticaria in the Second Half of 2026 Company to Host Conference Call and Webcast on Monday, March 2, 2026, at 8:00 a.m. ET SOUTH SAN FRANCISCO, Calif., March 01, 2026 (GLOBE NEWSWIRE) -- Septerna, Inc. (Nasdaq: SEPN), a clinical-stage biotechnology company pioneering oral small molecule GPCR-targeted medicines, today announced positive results from its Phase 1 clinical trial evaluating SEP-631, a potent and selective oral negative allosteric modulator (NAM) of Mas-related G protein-coupled receptor X2 (MRGPRX2). Based on these results, Septerna plans to advance SEP-631 into Phase 2 development for chronic spontaneous urticaria (CSU) and continue evaluation of additional mast cell-driven indications. “These data mark an important milestone for the SEP-631 program and more broadly for our Native Complex Platform®, which enables new approaches to GPCR drug discovery by reconstituting functional GPCR complexes outside of cells,” said Jae Kim, M.D., chief medical officer of Septerna. “Importantly, the robust inhibition of icatibant-induced wheal formation observed is consistent with the differentiated insurmountable NAM mechanism we characterized preclinically and provides clinical proof-of-mechanism for the MRGPRX2 pathway. Overall, we believe the strength and consistency of these results position SEP-631 as a potentially differentiated oral treatment for patients living with mast cell-driven diseases. With a clear path into Phase 2 development in chronic spontaneous urticaria, we are focused on translating this early validation into meaningful outcomes for patients and exploring additional high-need indications where MRGPRX2 biology is implicated.” Phase 1 Results SEP-631 was evaluated in a randomized, double-blind, placebo-controlled Phase 1 trial in healthy volunteers, including single-ascending dose, multiple-ascending dose and food-effect cohorts. The study assessed safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) activity. SEP-631 was well-tolerated across all doses studied: Adverse event profile comparable to placeboNo severe or serious adverse eventsNo clinically meaningful laboratory or ECG abnormalities SEP-631 demonstrated a PK profile supportive of convenient once-daily oral dosing, including: Half-life of approximately 24 hoursNo clinically meaningful effect of food on exposure, supporting dosing without food restrictions Pharmacodynamic activity was assessed using icatibant-induced skin wheal formation, an established skin test used to measure mast cell activation and target engagement, as a translational model of MRGPRX2-mediated mast cell activation. Use of short-wave infrared imaging technology enabled accurate and precise measurement of the skin test wheals. SEP-631 produced robust suppression of wheal formation across evaluated dose levels, with complete inhibition observed at doses as low as 10 mg once daily following the 10 µg/mL icatibant challenge. Following the 100 µg/mL icatibant challenge, inhibition was dose-dependent, with progressively greater suppression observed at increasing SEP-631 doses with near to complete inhibition achieved at 90 and 200 mg once daily. These findings are consistent with the insurmountable NAM mechanism of SEP-631 observed preclinically and support potent target engagement and functional blockade of MRGPRX2 signaling in humans, providing clinical proof-of-mechanism. Phase 2 Development Strategy Septerna plans to initiate a Phase 2b clinical trial of SEP-631 in chronic spontaneous urticaria (CSU) in the second half of this year, following the completion of ongoing long-term toxicology studies. The planned Phase 2b study will be a randomized, double-blind, placebo-controlled, global trial evaluating once-daily oral SEP-631 in adult patients with moderate-to-severe CSU who remain symptomatic despite treatment with second-generation antihistamines. Following the CSU study initiation, the company also plans to pursue an open-label study in chronic inducible urticaria (CIndU), specifically in patients with symptomatic dermatographism. Beyond urticaria, Septerna is evaluating additional mast cell-driven diseases with high unmet medical need and evidence of MRGPRX2 expression, and has initially prioritized atopic dermatitis, interstitial cystitis, migraine and asthma for further assessment. Conference Call and Webcast InformationSepterna will host a conference call and webcast on Monday, March 2, 2026, at 8:00 a.m. ET to discuss the Phase 1 results and initial Phase 2 development strategy for SEP-631. The live webcast will be available in the investors section of the company’s website at www.septerna.com. A replay will be available shortly after the event and will be archived for at least 30 days. About SEP-631Septerna is developing SEP-631, a selective oral small molecule Mas-related G protein-coupled receptor X2 (MRGPRX2) negative allosteric modulator (NAM) for the treatment of patients with chronic spontaneous urticaria (CSU) and other mast-cell driven diseases. MRGPRX2 is known to play an important role in mast cell activation and degranulation which, in combination with other inflammatory mediators, lead to debilitating symptoms for patients. In a Phase 1 clinical trial, SEP-631 demonstrated favorable tolerability, once-daily pharmacokinetics and pharmacodynamic evidence of MRGPRX2 pathway inhibition. Septerna plans to advance SEP-631 into Phase 2 development in CSU and chronic inducible urticaria and is evaluating its potential in additional mast cell-driven indications, including atopic dermatitis, interstitial cystitis, migraine and asthma. About SepternaSepterna, Inc. is a clinical-stage biotechnology company with a world-class team of GPCR experts and drug developers advancing cutting-edge science to unlock the full potential of GPCR therapies for patients with significant unmet needs. The company’s proprietary Native Complex Platform® is designed to enable new approaches to GPCR drug discovery and has led to the development of a diverse pipeline of novel oral small molecule drug candidates. Septerna is advancing programs in endocrinology, immunology and inflammation, metabolic diseases and additional therapeutic areas, both independently and with partners. For more information, please visit www.septerna.com. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements about Septerna’s beliefs and expectations regarding: the continued advancement of SEP-631, including the plan to initiate a Phase 2b clinical study in CSU in the second half of 2026 subject to the successful completion of long-term preclinical toxicology studies; the role of MRGPRX2 in mast cell-driven diseases; the potential of SEP-631 to provide a convenient oral treatment option for patients with CSU and other mast cell-driven diseases; expectations regarding the anticipated once-daily dosing frequency of SEP-631; the ability of the SEP-631 Phase 1 safety and efficacy observations to successfully translate into clinical outcomes in patients; the potential of its proprietary Native Complex Platform®; the size and growth potential of the markets for its current and future product candidates; its expectations regarding strategic plans for its business, product candidates, and technology; and the scope of protection it is able to establish and maintain for intellectual property rights covering its Native Complex Platform® and its product candidates. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “might,” “objective,” “ongoing,” “plan,” “predict,” “project,” “potential,” “should,” or “would,” or the negative of these terms, or other comparable terminology are intended to identify forward-looking statements, although not all forward looking statements contain these identifying words. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks associated with: Septerna’s product candidates successfully entering and advancing through clinical trials (including SEP-631) including uncertainties related to opening INDs and other regulatory approvals; risks related to clinical development outcomes including unexpected safety or efficacy findings; the results of preclinical studies including the long-term toxicology studies for SEP-631, or clinical studies not being predictive of future clinical outcomes; risks related to the timing of initiating clinical studies and future availability of clinical data; and the scope of protection Septerna is able to establish and maintain for intellectual property rights covering its Native Complex Platform® and its product candidates. These and other risks and uncertainties are described in greater detail in the section entitled “Risk Factors” in Septerna’s Annual Report on Form 10-K for the year ended December 31, 2024, as well as any subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent Septerna’s views only as of today and should not be relied upon as representing its views as of any subsequent date. Septerna explicitly disclaims any obligation to update any forward-looking statements subject to any obligations under applicable law. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Investor Contact:Renee Leck, THRUSTrenee@thrustsc.com Media Contact:Carly Scaduto, THRUSTcarly@thrustsc.com

Phase 1Clinical ResultPhase 2

100 Deals associated with Icatibant Acetate

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KEGG	Wiki	ATC	Drug Bank
D04492	Icatibant Acetate	B06AC02	DB06196

R&D Status

Approved

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Indication	Country/Location	Organization	Date
Hereditary Angioedema	European Union	Takeda Pharmaceuticals International AG	11 Jul 2008
Hereditary Angioedema	Iceland	Takeda Pharmaceuticals International AG	11 Jul 2008
Hereditary Angioedema	Liechtenstein	Takeda Pharmaceuticals International AG	11 Jul 2008
Hereditary Angioedema	Norway	Takeda Pharmaceuticals International AG	11 Jul 2008
Hereditary Angioedema Types I and II	European Union	Takeda Pharmaceuticals International AG	11 Jul 2008
Hereditary Angioedema Types I and II	Iceland	Takeda Pharmaceuticals International AG	11 Jul 2008
Hereditary Angioedema Types I and II	Liechtenstein	Takeda Pharmaceuticals International AG	11 Jul 2008
Hereditary Angioedema Types I and II	Norway	Takeda Pharmaceuticals International AG	11 Jul 2008

Developing

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Indication	Highest Phase	Country/Location	Organization	Date
Angioedema	Phase 3	United States	Shire Plc	02 Dec 2013
Angioedema	Phase 3	Canada	Shire Plc	02 Dec 2013
Angioedema	Phase 3	Israel	Shire Plc	02 Dec 2013
Angioedema	Phase 3	United Kingdom	Shire Plc	02 Dec 2013
Osteoarthritis, Knee	Phase 3	Slovakia	Sanofi-Aventis Recherche & Développement SA	17 May 2007
Musculoskeletal Pain	Phase 2	European Union	Hoechst Pakistan Ltd.	-
Pancreatitis	Phase 2	Germany	Hoechst Pakistan Ltd.	-
Rhinitis	Phase 2	United States	Hoechst Pakistan Ltd.	-
Rhinitis	Phase 2	Australia	Hoechst Pakistan Ltd.	-
Rhinitis	Phase 2	New Zealand	Hoechst Pakistan Ltd.	-

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04978051 (ICAT·COVID, Pubmed)	Phase 2	COVID-19	73	Icatibant + standard care	yxilhpemon(mkavcuzjul) = erryobyuyt focdwnrrxo (twraksijsn ) View more	Positive	04 Jan 2023
NCT04978051 (ICAT·COVID, Pubmed)	Phase 2	COVID-19	73	icatibant (Standard care alone)	yxilhpemon(mkavcuzjul) = asxhhddhqo focdwnrrxo (twraksijsn ) View more	Positive	04 Jan 2023
NCT04654351 (CTgov)	Phase 3	Hereditary Angioedema Types I and II \| Hereditary Angioedema	2	TAK-667	zzqogmgidd = bmpotckkbh hutqxluwhy (jduttpxhtp, ilrcdudyjp - xrjwiwgcus) View more	-	29 Mar 2022
NCT03888755 (Pubmed \| Allergol Int) Manual	Phase 3	Hereditary Angioedema	8	icatibant	ucjmvxlkjv(sibamgthzk) = arruwzctxa mhbokhbdzh (eagexhbcnv, 1.00 - 2.50)	Positive	01 Apr 2020
NCT03177798 (MitoCKD, CTgov)	Phase 2	Mitochondrial Diseases \| Nephrosis \| Chronic Kidney Diseases	11	Icatibant (Icatibant)	funuyynuxy(seoswvsjcb) = hbdwlwahoh fupnrljrap (dcfiudbwnc, 13.94) View more	-	29 Oct 2019
NCT03177798 (MitoCKD, CTgov)	Phase 2		11	placebo+Icatibant (Placebo)	funuyynuxy(seoswvsjcb) = vvfautpgzj fupnrljrap (dcfiudbwnc, 29.4) View more	-	29 Oct 2019
NCT03888755 (CTgov)	Phase 3	Hereditary Angioedema Types I and II \| Hereditary Angioedema	8	Icatibant	wunxcgmlpq(pclqpwzzek) = ltdqmtuqpo hznyncpmtv (ctfqgaxccm, erwqojrrrs - mwgzwkzixd) View more	-	08 Aug 2019
NCT01386658 (CTgov)	Phase 3	Hereditary Angioedema Types I and II \| Hereditary Angioedema	32	icatibant (Prepubertal)	ckwcmavwpn(hoejlnsibu) = jimmvfezsg haaabmdqpm (pupyzyadjh, 0.13) View more	-	25 Mar 2019
NCT01386658 (CTgov)	Phase 3		32	icatibant (Pubertal/Postpubertal: With Acute Attack)	ckwcmavwpn(hoejlnsibu) = hnqhribkfv haaabmdqpm (pupyzyadjh, 0.19) View more	-	25 Mar 2019
NCT01386658 (Pubmed \| J Allergy Clin Immunol Pract) Manual	Phase 3	Hereditary Angioedema	32	Icatibant	bpqzdmtvab(mqqffgrikd) = srleejwkjc jrexeenlsd (ypvaolsxox ) View more	Positive	01 Nov 2017
NCT01574248 (CTgov)	Phase 4	Angioedema	33	icatibant (Icatibant)	mruqjqjzln(hzhbqhudpo) = qagclyngzq nudjpumwpb (boghzsnzrn, nkherldkwm - ddvmyyufap) View more	-	17 Feb 2017
NCT01574248 (CTgov)	Phase 4	Angioedema	33	Placebo (Placebo)	mruqjqjzln(hzhbqhudpo) = wddavtbkmf nudjpumwpb (boghzsnzrn, zeytujvagi - rrthlwrzqm) View more	-	17 Feb 2017
NCT01457430 (IHA, CTgov)	Phase 4	Hereditary Angioedema Types I and II \| Hereditary Angioedema	19	Icatibant	sjfyedapzt(hljwqsucnd) = gzldxngscv xbasajergm (jcgnzdmnni, moghlqsdvi - diokwqswhk) View more	-	18 Oct 2016
NCT01919801 (CTgov)	Phase 3	Angioedema	118	Placebo	tjpyzkrtgz(jrqukarpjq) = vwfywmwryw kfdplypdcz (hsrvqxvugb, xulwboyhze - tungglrinw) View more	-	10 Oct 2016

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