A Phase 1, Open-label, Parallel-group Study to Assess the Effect of Steady-state Carbamazepine on the Pharmacokinetics of Ponesimod in Healthy Adult Participants

The purpose of this study is to evaluate the effect of steady-state carbamazepine (CBZ; a strong pregnane X receptor [PXR] agonist) on the pharmacokinetics (PK) of ponesimod following a gradual up-titration regimen in healthy adult participants.

Start Date18 Oct 2022

Sponsor / Collaborator

Janssen Pharmaceutica NV

NCT05688436

/ RecruitingNot Applicable

Pregnancy Outcomes in Women Exposed to Diroximel Fumarate

The primary objective of the study is to estimate the prevalence of major congenital malformations (MCMs) and compare the prevalence between the diroximel fumarate (DRF) and comparator groups. The secondary objectives of the study are to estimate the incidence of spontaneous abortion (SA) and compare the incidence between the DRF and comparator groups; to estimate the incidence of preterm birth and compare the incidence between the DRF and comparator groups; to estimate the incidence of stillbirth and compare the incidence between the DRF and comparator groups and to estimate the prevalence of small for gestational age (SGA) and compare the prevalence between the DRF and comparator groups.

Start Date24 Sep 2021

Sponsor / Collaborator

Biogen, Inc.

NCT03882255

/ CompletedPhase 1

A Randomized, Double-blind, Parallel-group, 2-period, Placebo-controlled, Phase 1 Study to Investigate the Effects on Heart Rate, Blood Pressure, and Pharmacokinetic Interactions of the Up-titration Regimen of Ponesimod in Healthy Adult Subjects Receiving Propranolol at Steady State

The primary purpose of this study is to evaluate the effect of the up-titration regimen of ponesimod on heart rate (HR) and other electrocardiogram (ECG) parameters when administrated to healthy adult participants receiving propranolol at steady state.

Start Date20 Mar 2019

Sponsor / Collaborator

Janssen Pharmaceutica NV

100 Clinical Results associated with Ponesimod

100 Translational Medicine associated with Ponesimod

100 Patents (Medical) associated with Ponesimod

147

Literatures (Medical) associated with Ponesimod

01 Feb 2025·MOLECULAR IMAGING AND BIOLOGY

PET Imaging of Sphingosine-1-Phosphate Receptor 1 with [18F]TZ4877 in Nonhuman Primates

Article

Author: Huang, Yiyun ; Zheng, Ming-Qiang ; Qiu, Lin ; Hillmer, Ansel T ; Zhang, Li ; Fowles, Krista ; Gu, Jiwei ; Holden, Daniel ; Carson, Richard E ; Gropler, Robert J ; Ropchan, Jim ; Felchner, Zachary ; Tu, Zhude

PURPOSE:

The sphingosine-1-phosphate receptor-1 (S1PR₁) is involved in regulating responses to neuroimmune stimuli. There is a need for S1PR₁-specific radioligands with clinically suitable brain pharmcokinetic properties to complement existing radiotracers. This work evaluated a promising S1PR₁ radiotracer, [¹⁸F]TZ4877, in nonhuman primates.

PROCEDURES:

[¹⁸F]TZ4877 was produced via nucleophilic substitution of tosylate precursor with K[¹⁸F]/F^- followed by deprotection. Brain PET imaging data were acquired with a Focus220 scanner in two Macaca mulatta (6, 13 years old) for 120-180 min following bolus injection of 118-163 MBq [¹⁸F]TZ4877, with arterial blood sampling and metabolite analysis to measure the parent input function and plasma free fraction (f_P). Each animal was scanned at baseline, 15-18 min after 0.047-0.063 mg/kg of the S1PR₁ inhibitor ponesimod, 33 min after 0.4-0.8 mg/kg of the S1PR₁-specific compound TZ82112, and 167-195 min after 1 ng/kg of the immune stimulus endotoxin. Kinetic analysis with metabolite-corrected input function was performed to estimate the free fraction corrected total distribution volume (V_T/f_P). Whole-body dosimetry scans were acquired in 2 animals (1M, 1F) with a Biograph Vision PET/CT System, and absorbed radiation dose estimates were calculated with OLINDA.

RESULTS:

[¹⁸F]TZ4877 exhibited fast kinetics that were described by the reversible 2-tissue compartment model. Baseline [¹⁸F]TZ4877 f_P was low (<1%), and [¹⁸F]TZ4877 V_T/f_P values were 233-866 mL/cm³. TZ82112 dose-dependently reduced [¹⁸F]TZ4877 V_T/f_P, while ponesimod and endotoxin exhibited negligible effects on V_T/f_P, possibly due to scan timing relative to dosing. Dosimetry studies identified the critical organs of gallbladder (0.42 (M) and 0.31 (F) mSv/MBq) for anesthetized nonhuman primate.

CONCLUSIONS:

[¹⁸F]TZ4877 exhibits reversible kinetic properties, but the low f_P value limits reproducible quantification with this radiotracer. S1PR₁ is a compelling PET imaging target, and these data support pursuing alternative F-18 labeled radiotracers for potential future human studies.

01 Dec 2024·CURRENT TOPICS IN MEDICINAL CHEMISTRY

The Current Landscape in the Development of Small-molecule Modulators Targeting Sphingosine-1-phosphate Receptors to Treat Neurodegenerative Diseases

Review

Author: Sahu, Sujit Kumar ; Kar, Sidhartha Sankar ; Gharai, Soumya Ranjan ; Swain, Sharada Prasanna ; Ravichandiran, Velayutham

Sphingosine 1-phosphate (S1P) is extensively researched as a lysophospholipid and is crucial in various physiological and pathological processes. It achieves this via signalling through five different subtypes of G protein-coupled receptors (GPCRs), namely S1PR1 to S1PR5. S1PR modulators possess the ability to traverse the blood-brain barrier, potentially leading to direct actions within the Central Nervous System (CNS). S1PR modulators specifically bind to receptors located on the surface of naive and central memory lymphocytes, causing these cells to be trapped or confined within the lymph node. The investigation of the S1P pathway has resulted in the approval of three S1PR modulators, namely fingolimod, siponimod, and ozanimod, as medications for the treatment of patients suffering from Multiple Sclerosis (MS). Additionally, new S1PR modulators, such as ponesimod and etrasimod, are currently being developed and tested in clinical trials. Research on the creation of S1P modulators in neurodegenerative illnesses is ongoing as scientists continue to explore novel possibilities for selective S1P modulators. This study provides a concise overview of sphingolipid metabolism, the mechanism by which S1P receptors are affected, and the structural characteristics of several small molecule S1P modulators, with a particular focus on their structure-activity connections.

28 Nov 2024·Cureus Journal of Medical Science

Exploring Public Interest in Multiple Sclerosis and Its Treatment Measures in the United States: A Google Trends Analysis

Article

Author: Angadala, Sai K ; Phillips, Vidith ; Aluri, Pruthvi Sai Chowdary ; Puvvada, Chaitanya S ; Ansari, Yusuf-Zain A ; Singh, Jaskaran ; Siddiqui, Zaed S ; Deoghare, Shreya

Introduction Multiple sclerosis (MS) afflicts over 2.8 million individuals worldwide and is a leading cause of neurological impairment in young adults. This study investigates the public interest in MS and its treatment options in the United States over the past decade, utilizing Google Trends data. The aim is to analyze how search trends reflect public engagement with MS, particularly about managing relapses, slowing disease progression, alleviating symptoms, and enhancing quality of life. Methods A cross-sectional study was conducted utilizing Google Trends to analyze search interest related to MS and its treatments from January 2014 to December 2023. The data was divided into two five-year periods: 2014-2018 and 2019-2023. Specific search terms for MS and various treatment modalities were analyzed, including traditional therapies (e.g., interferon-beta, glatiramer acetate) and newer treatments (e.g., ocrelizumab, siponimod). Statistical analysis was performed using the Mann-Whitney U test to compare relative search volumes (RSV) between the two periods. Results Significant fluctuations in RSV were observed over the study period. A notable increase in RSV was found for treatments such as rituximab, ocrelizumab, ublituximab, siponimod, and ponesimod in the 2019-2023 period compared to 2014-2018 (p < 0.05). Conversely, a significant decrease in RSV was observed for glatiramer acetate, alemtuzumab, natalizumab, fingolimod, and plasmapheresis during the same periods (p < 0.05). Treatments like beta interferon, ofatumumab, and teriflunomide showed no significant change in RSV between the two periods (p > 0.05). Conclusion Dividing the search period into two five-year intervals revealed shifting public interest toward newer MS therapies over the past decade. The increased interest in recent treatments aligns with advancements in MS management and may influence patient inquiries and treatment decisions. These findings highlight the utility of Google Trends as a tool for monitoring public awareness and underscore the importance of providing accessible, accurate information to guide healthcare strategies and policymaking.

News (Medical) associated with Ponesimod

13 Feb 2025

·www.prnewswire.com

Vanda Pharmaceuticals Reports Fourth Quarter and Full Year 2024 Financial Results

Q4 2024 total revenues of $53.2 million, +17% compared to Q4 2023 Q4 2024 Fanapt® net product sales of $26.6 million, +18% compared to Q4 2023 Full year 2024 total revenues of $198.8 million, +3% compared to full year 2023 Full year 2025 revenue expected to grow to $210 to $250 million Psychiatry portfolio revenue expected to grow to greater than $750 million in 2030 Fanapt® MAA for bipolar I disorder and schizophrenia submitted in Q4 2024 BysantiTM (milsaperidone) NDA for bipolar I disorder and schizophrenia expected to be submitted in Q1 2025 HETLIOZ® MAA for Smith-Magenis syndrome submitted in Q4 2024 Tradipitant NDA for motion sickness submitted in Q4 2024 Imsidolimab BLA in generalized pustular psoriasis expected to be submitted in 2025 WASHINGTON, Feb. 13, 2025 /PRNewswire/ -- Vanda Pharmaceuticals Inc. (Vanda) (Nasdaq: VNDA) today announced financial and operational results for the fourth quarter and full year ended December 31, 2024. "Strong revenue growth for Fanapt is putting us on a significant growth trajectory for 2025 and beyond, supported also by the commercial performance of Hetlioz and Ponvory. The Fanapt long acting injectable program, the NDA for Bysanti for bipolar disorder and schizophrenia along with its development for major depressive disorder have the potential to drive future growth in our psychiatry portfolio for many years to come," said Mihael H. Polymeropoulos, M.D., Vanda's President, CEO and Chairman of the Board. "Tradipitant's NDA for motion sickness was filed with a potential approval this year, while we are pursuing approval in gastroparesis and the development of tradipitant to improve tolerability of GLP-1 analog Wegovy. Our anti-inflammatory portfolio, anchored by Ponvory, was strengthened with the addition of imsidolimab from Anaptys, an IL-36 receptor inhibitor for the treatment of generalized pustular psoriasis. We plan to file a BLA later this year while we are exploring registration in Europe and Japan as well as the development of this novel drug for other inflammatory disorders with an unopposed action of the IL-36 system. In 2024 we returned to revenue growth driven by the commercial launches in bipolar disorder and multiple sclerosis and advanced our development pipeline with a number of products at or near marketing applications. All this was achieved by the hard work, ingenuity and efficiency of our organization and its wonderful people." Financial Highlights Fourth Quarter of 2024 Total net product sales from Fanapt®, HETLIOZ® and PONVORY® were $53.2 million in the fourth quarter of 2024, a 17% increase compared to $45.3 million in the fourth quarter of 2023 and a 12% increase compared to $47.7 million in the third quarter of 2024. Fanapt® net product sales were $26.6 million in the fourth quarter of 2024, an 18% increase compared to $22.6 million in the fourth quarter of 2023 and an 11% increase compared to $23.9 million in the third quarter of 2024. HETLIOZ® net product sales were $20.0 million in the fourth quarter of 2024, a 5% decrease compared to $21.1 million in the fourth quarter of 2023 and a 12% increase compared to $17.9 million in the third quarter of 2024. PONVORY® net product sales were $6.5 million in the fourth quarter of 2024, an increase of 11% compared to $5.9 million in the third quarter of 2024. The acquisition of PONVORY® from Actelion Pharmaceuticals Ltd. (Janssen), a Johnson & Johnson Company, was completed on December 7, 2023. Net loss was $4.9 million in the fourth quarter of 2024 compared to net loss of $2.4 million in the fourth quarter of 2023 and net loss of $5.3 million in the third quarter of 2024. Cash, cash equivalents and marketable securities (Cash) was $374.6 million as of December 31, 2024, representing a decrease to Cash of $1.6 million compared to September 30, 2024. Full Year 2024 Total net product sales from Fanapt®, HETLIOZ® and PONVORY® were $198.8 million for the full year 2024, a 3% increase compared to $192.6 million for the full year 2023. Fanapt® net product sales were $94.3 million for the full year 2024, a 4% increase compared to $90.9 million for the full year 2023. HETLIOZ® net product sales were $76.7 million for the full year 2024, a 23% decrease compared to $100.2 million for the full year 2023. The decrease relative to the full year 2023 was the result of continued generic competition in the U.S. PONVORY® net product sales were $27.8 million for the full year 2024. The acquisition of PONVORY® from Janssen was completed on December 7, 2023. Net loss was $18.9 million for the full year 2024, compared to net income of $2.5 million for the full year 2023. Cash was $374.6 million as of December 31, 2024, representing a decrease to Cash of $13.6 million compared to December 31, 2023. Key Operational Highlights Fanapt® (iloperidone) Fanapt® was approved in the second quarter of 2024 for the acute treatment of bipolar I disorder. Vanda initiated the commercial launch of Fanapt® in this indication in the third quarter of 2024. In the fourth quarter of 2024, as compared to the fourth quarter of 2023, new patient starts, as reflected by new to brand prescriptions (NBRx),1 increased by over 160% and Fanapt® net product sales increased by 18%. Vanda initiated a Phase III program for the long acting injectable (LAI) formulation of Fanapt® in the fourth quarter of 2024. Vanda plans to initiate a study of the Fanapt® LAI as a once-a-month injectable for the treatment of hypertension to address both treatment resistance and treatment compliance. Vanda submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in the fourth quarter of 2024 for Fanapt® for bipolar I disorder and schizophrenia. Bysanti™ (milsaperidone) Vanda expects to submit a New Drug Application (NDA) for Bysanti™ to the U.S. Food and Drug Administration (FDA) for the treatments of acute bipolar I disorder and schizophrenia in the first quarter of 2025. Exclusivity, including pending patent applications, could extend into the 2040s. Vanda initiated a Phase III clinical study for Bysanti™ as a once-daily adjunctive treatment for major depressive disorder (MDD) in the fourth quarter of 2024. Results are expected in 2026. HETLIOZ® (tasimelteon) Vanda has initiated clinical programs for HETLIOZ® in pediatric insomnia and delayed sleep phase disorder (DSPD) and these programs are ongoing. Vanda's MAA for HETLIOZ® and HETLIOZ LQ® for Smith-Magenis Syndrome (SMS) is pending with the EMA. PONVORY® (ponesimod) Vanda initiated the commercial launch of PONVORY® for the treatment of relapsing forms of multiple sclerosis in the third quarter of 2024. Investigational New Drug (IND) applications for PONVORY® in the treatments of psoriasis and ulcerative colitis were accepted by the FDA in the fourth quarter of 2024. Tradipitant The NDA for tradipitant for the treatment of motion sickness was submitted to the FDA in the fourth quarter of 2024. Vanda initiated a clinical trial to study tradipitant in the prevention of vomiting induced by a GLP-1 analog, Wegovy (semaglutide), in the fourth quarter of 2024. Vanda has accepted the opportunity for a hearing with the FDA on the approvability of the NDA for tradipitant for the treatment of symptoms of gastroparesis. Imsidolimab In February 2025, Vanda announced it entered into an exclusive, global license agreement with AnaptysBio, Inc. (Anaptys) for the development and commercialization of imsidolimab (IL-36R antagonist mAb). Vanda expects to initiate and complete the technology transfer activities in 2025 and immediately begin preparing the Biologics License Application (BLA) and MAA for generalized pustular psoriasis (GPP) for the US and EU. The imsidolimab BLA for GPP is expected to be submitted to the FDA in 2025. Early-Stage Program Highlights VQW-765, an alpha-7 nicotinic acetylcholine receptor partial agonist, is currently in clinical development for the treatment of acute performance anxiety in social situations. Vanda expects to initiate a Phase III program in 2025. The IND application for VCA-894A in the treatment of Charcot-Marie-Tooth disease, axonal, type 2S (CMT2S), an inherited peripheral neuropathy for which there is no available treatment, was accepted by the FDA in 2024. Previously in 2023, VCA-894A was granted Orphan Drug Designation for the same indication. The Phase I clinical study for VCA-894A expects to enroll the patient by mid-2025. In December 2024, Vanda announced that the FDA has granted Orphan Drug Designation for VGT-1849A, a selective antisense oligonucleotide (ASO)-based JAK2 inhibitor for the treatment of polycythemia vera (PV), a form of a rare hematologic malignancy that is estimated to affect 1 in 2,000 Americans. Key Regulatory Milestones Tradipitant NDA for motion sickness submitted in Q4 2024. Fanapt® MAA for bipolar I disorder and schizophrenia submitted in Q4 2024. HETLIOZ® MAA in Smith-Magenis syndrome (SMS) submitted in Q4 2024. Bysanti™ NDA for bipolar I disorder and schizophrenia expected to be submitted in Q1 2025. Imsidolimab BLA in generalized pustular psoriasis expected to be submitted in 2025. GAAP Financial Results Net loss was $4.9 million in the fourth quarter of 2024 compared to net loss of $2.4 million in the fourth quarter of 2023. Diluted net loss per share was $0.08 in the fourth quarter of 2024 compared to diluted net loss per share of $0.04 in the fourth quarter of 2023. Net loss was $18.9 million for the full year 2024 compared to net income of $2.5 million for the full year 2023. Diluted net loss per share was $0.33 for the full year 2024 compared to diluted net income per share of $0.04 for the full year 2023. 2025 Financial Guidance and 2030 Revenue Targets Vanda expects to achieve the following financial objectives in 2025: Vanda is providing 2030 revenue targets. For the psychiatry portfolio alone, Vanda is targeting annual revenue in excess of $750 million in 2030, assuming the potential approval of Bysanti™ for the treatments of acute bipolar I disorder and schizophrenia in early 2026, the potential approval of Bysanti™ for the treatment of MDD, and the potential approval of Fanapt® LAI. Vanda is also targeting total annual revenue in excess of $1 billion in 2030. Conference Call Vanda has scheduled a conference call for today, Thursday, February 13, 2025, at 4:30 PM ET. During the call, Vanda's management will discuss the fourth quarter and full year 2024 financial results and other corporate activities. Investors can call 1-800-715-9871 (domestic) or 1-646-307-1963 (international) and use passcode number 2881765. A replay of the call will be available on Thursday, February 13, 2025, beginning at 8:30 PM ET and will be accessible until Thursday, February 20, 2025 at 11:59 PM ET. The replay call-in number is 1-800-770-2030 for domestic callers and 1-609-800-9909 for international callers. The passcode number is 2881765. The conference call will be broadcast simultaneously on Vanda's website, . Investors should click on the Investors tab and are advised to go to the website at least 15 minutes early to register, download, and install any necessary software or presentations. The call will also be archived on Vanda's website for a period of 30 days. References IQVIA Prescription Data About Vanda Pharmaceuticals Inc. Vanda is a leading global biopharmaceutical company focused on the development and commercialization of innovative therapies to address high unmet medical needs and improve the lives of patients. For more on Vanda Pharmaceuticals Inc., please visit and follow us on X @vandapharma. CAUTIONARY NOTE REGARDING FORWARD LOOKING STATEMENTS Various statements in this press release, including, but not limited to, the guidance provided under "2025 Financial Guidance and 2030 Revenue Targets" above and the related implied growth of Vanda's business, and statements regarding Vanda's plans for pursuit of FDA approval of BysantiTM for the treatments of acute bipolar I disorder and schizophrenia and imsidolimab for the treatment of GPP, and the related timelines; Vanda's expectations with respect to the growth opportunities for its psychiatry frachise; Vanda's consideration of foreign regulatory approval for imsidolimab and its potential development for other inflammatory disorders; Vanda's clinical development plans and expected timelines for Fanapt® LAI, BysantiTM for the treatment of MDD, VQW-765 for the treatment of acute performance anxiety in social situations, and VCA-894A for the treatment of CMT2S; the commercial and therapeutic potential for BysantiTM; the potential to extend patent exclusivity for BysantiTM into the 2040s; the anticipated timing of the initiation and completion of technology transfer activities and the preparation of regulatory filings in the US and EU for imsidolimab; and the prevalence of PV are "forward-looking statements" under the securities laws. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. Forward-looking statements are based upon current expectations and assumptions that involve risks, changes in circumstances and uncertainties. Important factors that could cause actual results to differ materially from those reflected in Vanda's forward-looking statements include, among others, Vanda's ability to continue to grow its psychiatry portfolio and overall business; the results of Vanda's review of foreign regulatory opportunities for imsidolmab; Vanda's ability to identify additional indications for imsidolimab; Vanda's ability to complete and submit to the FDA the NDA for BysantiTM for the treatments of acute bipolar I disorder and schizophrenia in the first quarter of 2025; Vanda's ability to complete and submit the BLA for imsidolimab for the treatment of GPP in 2025; Vanda's ability to complete the Phase III clinical study for BysantiTM for MDD and receive results in 2026; Vanda's ability to initiate the Phase III program for VQW-765 in 2025; Vanda's ability to enroll the CMT2S patient in the Phase I clinical study for VCA-894A by mid-2025; Vanda's ability to complete the clinical development of, obtain regulatory approval for, and successfully commercialize, BysantiTM for the treatments of acute bipolar I disorder, schizophrenia and MDD; Vanda's ability to satisfy the conditions necessary to extend BysantiTM's patent exclusivity into the 2040s; Vanda's ability to initiate and complete the technology transfer activities and prepare the BLA and MAA for imsidolimab in the specified timeframes; and the accuracy of the estimate regarding the prevalence of PV. Therefore, no assurance can be given that the results or developments anticipated by Vanda will be realized or, even if substantially realized, that they will have the expected consequences to, or effects on, Vanda. Forward-looking statements in this press release should be evaluated together with the various risks and uncertainties that affect Vanda's business and market, particularly those identified in the "Cautionary Note Regarding Forward-Looking Statements", "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" sections of Vanda's most recent Annual Report on Form 10-K, as updated by Vanda's subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the U.S. Securities and Exchange Commission, which are available at . All written and verbal forward-looking statements attributable to Vanda or any person acting on its behalf are expressly qualified in their entirety by the cautionary statements contained or referred to herein. Vanda cautions investors not to rely too heavily on the forward-looking statements Vanda makes or that are made on its behalf. The information in this press release is provided only as of the date of this press release, and Vanda undertakes no obligation, and specifically declines any obligation, to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. Corporate Contact: Kevin Moran Senior Vice President, Chief Financial Officer and Treasurer Vanda Pharmaceuticals Inc. 202-734-3400 [email protected] Jim Golden / Jack Kelleher / Dan Moore Collected Strategies [email protected] Follow us on X @vandapharma SOURCE Vanda Pharmaceuticals Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

License out/inDrug ApprovalNDAPhase 1Phase 3

03 Feb 2025

·pipelinereview.com

Vanda Pharmaceuticals and Anaptys Announce Exclusive Global License Agreement for Vanda to Develop and Commercialize Imsidolimab, an IL-36R Antagonist

WASHINGTON, DC and SAN DIEGO, CA, USA I February 3, 2025 I Vanda Pharmaceuticals Inc. (Vanda) (Nasdaq: VNDA ) and AnaptysBio, Inc. (Anaptys) (Nasdaq: ANAB ) today announced an exclusive, global license agreement for the development and commercialization of imsidolimab (IL-36R antagonist mAb), which has successfully completed two registration-enabling global Phase 3 trials, GEMINI-1 and GEMINI-2, evaluating the safety and efficacy of imsidolimab in patients with Generalized Pustular Psoriasis (GPP). GPP is a rare skin disorder often caused by mutations in the IL36RN gene that codes for a regulatory protein that balances the activity of the proinflammatory IL-36 family of cytokines. Dysregulation of this balance in IL-36 signaling leads to severe chronic skin inflammation with pustules and systemic symptoms which carry significant morbidity and mortality often associated with sepsis and multi-organ failure. 1 Imsidolimab inhibits the function of the IL-36R, compensating for the deficiency of the endogenous IL-36 regulator in patients with GPP. Imsidolimab has successfully concluded its development program in GPP, including the GEMINI-1 and GEMINI-2 global Phase 3 studies. In 2025, Vanda intends to initiate and complete the technology transfer activities and will immediately begin preparing the BLA and MAA applications for the US and EU and making preparations for commercialization. “We are excited to add imsidolimab to Vanda’s product portfolio for rare orphan disorders, as well as explore the potential of this IL-36 signal regulator in the treatment of additional inflammatory conditions where the IL-36 homeostatic balance is dysregulated,” said Mihael H. Polymeropoulos, M.D., Vanda’s President, CEO and Chairman of the Board. “Imsidolimab has great synergy with our commercial portfolio, leveraging both our rare disease expertise in the US and EU as well as the anti-inflammatory portfolio that includes Ponvory ® for multiple sclerosis, psoriasis and ulcerative colitis.” GPP prevalence estimates in the general population vary considerably, between 1.76 and 124 patients per million persons worldwide. 2 The majority of GPP cases are caused by genetic variants in IL36RN. 3,4 Loss-of-function mutations in IL36RN are mostly missense mutations in a recessive pattern and result in unrestricted IL-36 activity. 5,6 “GPP is a severely debilitating, life-threatening skin disease in need of novel therapeutic approaches,” said Johann Gudjonsson, M.D., Ph.D., Arthur C. Curtis Professor of Molecular Skin Immunology and Scholar of the Taubman Medical Research Institute, University of Michigan. “The positive Phase 3 data, demonstrating GPP patients achieved rapid disease clearance through Week 4 after a single dose of infused imsidolimab, and maintained clear to almost clear skin for at least 24 weeks, with no clinically meaningful safety signals, represents a promising new option for patients living with this disease. I’m excited imsidolimab is progressing toward a regulatory filing this year.” “Vanda is an ideal partner for imsidolimab due to their strong regulatory and commercial capabilities in the US and Europe, evidenced by successful recent launches in specialty and rare diseases, and their commitment to invest in label expansion across their therapeutic portfolio, including their growing presence in inflammatory disease,” said Daniel Faga, president and chief executive officer of Anaptys. “Following our productive pre-BLA meeting with FDA in 2024, we look forward to Vanda’s BLA and MAA submissions later in 2025, with the hope that this potentially differentiated therapeutic option will be made available for patients living with GPP, a burdensome, and sometimes life-threatening skin disease.” Under the terms of the agreement, Vanda will make to Anaptys an upfront payment of $10 million and a $5 million payment for existing drug supply. Anaptys is also eligible to receive up to $35 million for future regulatory approval and sales milestones in addition to a 10% royalty on net sales. Vanda will receive an exclusive global license to develop, manufacture and commercialize imsidolimab. Guggenheim Securities acted as financial advisor and Fenwick & West LLP served as legal counsel to Anaptys on this transaction. Cantor Fitzgerald & Co. acted as financial advisor and Orrick, Herrington & Sutcliffe LLP served as legal counsel to Vanda. About GEMINI-1 and GEMINI-2 Studies In the 45-patient GEMINI-1 Phase 3 trial, patients were randomized 1:1:1 to receive a single infusion of 750mg intravenous (IV) imsidolimab, 300mg IV imsidolimab or placebo at Day 0. Of the patients who received a single dose of 750mg IV imsidolimab, 53% achieved a GPP Physician Global Assessment (GPPPGA) score of 0/1 (clear or almost clear skin) at Week 4 (primary endpoint), compared to 13% of the patients on placebo (p=0.0131). Of the patients who received a single dose of 300mg IV imsidolimab, 53% achieved GPPPGA 0/1 at Week 4. Sixteen GPPPGA 0/1 responder patients from GEMINI-1 were subsequently re-randomized to monthly maintenance dosing of either 200mg subcutaneous (SC) imsidolimab or placebo in the GEMINI-2 Phase 3 trial. Patients were followed for at least 24 weeks and up to a maximum of 92 weeks. Of the eight responding patients from GEMINI-1 who were re-randomized to monthly 200mg SC imsidolimab maintenance therapy, 100% maintained a GPPPGA score of 0/1 and none of them experienced a flare. Of the remaining eight responding patients from GEMINI-1 who were re-randomized to placebo, 25% maintained a GPPPGA score of 0/1 and 63% experienced a flare. Data from both trials demonstrated a consistent, favorable safety and tolerability profile with no treatment-related serious adverse events (SAEs) or SAEs leading to discontinuation reported in imsidolimab-treated patients. About Imsidolimab and GPP Imsidolimab is a fully humanized IgG4 antibody that inhibits the function of the interleukin-36-receptor, or IL-36R, that is being developed for the treatment of GPP. Regulatory and patent exclusivity is expected to extend into the late 2030s. GPP is a rare, chronic, systemic autoinflammatory disease that is potentially life-threatening, if left untreated. During a GPP flare, individuals experience the sudden eruption of painful pustules. These pustules appear over large areas of the skin, accompanied by redness, severe itchiness, and dry, cracked, or scaly skin. People with GPP may also experience more general symptoms such as fever, headache, extreme tiredness, or a burning sensation on the skin. About Vanda Pharmaceuticals, Inc. Vanda is a leading global biopharmaceutical company focused on the development and commercialization of innovative therapies to address high unmet medical needs and improve the lives of patients. For more on Vanda Pharmaceuticals Inc., please visit www.vandapharma.com and follow us on X @vandapharma. About Anaptys Anaptys is a clinical-stage biotechnology company focused on delivering innovative immunology therapeutics for autoimmune and inflammatory diseases. Its lead program, rosnilimab, a depleter and agonist targeting PD-1+ T cells, is in a Phase 2b trial for the treatment of rheumatoid arthritis and in a Phase 2 trial for the treatment of ulcerative colitis. Other antibodies in its portfolio include ANB033, an anti-CD122 antagonist, in a Phase 1 trial and ANB101, a BDCA2 modulator, soon to enter clinical development. Anaptys has also discovered multiple therapeutic antibodies licensed to GSK in a financial collaboration for immuno-oncology, including an anti-PD-1 antagonist ( Jemperli (dostarlimab-gxly)) and an anti-TIM-3 antagonist (cobolimab, GSK4069889). To learn more, visit www.AnaptysBio.com or follow us on LinkedIn . References: SOURCE: Vanda Pharmaceuticals

Phase 3License out/inPhase 2Clinical ResultImmunotherapy

03 Feb 2025

·ir.anaptysbio.com

Vanda Pharmaceuticals and Anaptys Announce Exclusive Global License Agreement for Vanda to Develop and Commercialize Imsidolimab, an IL-36R Antagonist

Imsidolimab has successfully completed two global Phase 3 studies in Generalized Pustular Psoriasis Vanda expects to immediately begin preparing BLA and MAA applications for the US and EU Anaptys to receive $15 million from Vanda, comprised of a $10 million upfront payment and $5 million for existing drug supply Anaptys to receive a 10% royalty on global net sales of imsidolimab WASHINGTON and SAN DIEGO, Feb. 3, 2025 /PRNewswire/ -- Vanda Pharmaceuticals Inc. (Vanda) (Nasdaq: VNDA) and AnaptysBio, Inc. (Anaptys) (Nasdaq: ANAB) today announced an exclusive, global license agreement for the development and commercialization of imsidolimab (IL-36R antagonist mAb), which has successfully completed two registration-enabling global Phase 3 trials, GEMINI-1 and GEMINI-2, evaluating the safety and efficacy of imsidolimab in patients with Generalized Pustular Psoriasis (GPP). GPP is a rare skin disorder often caused by mutations in the IL36RN gene that codes for a regulatory protein that balances the activity of the proinflammatory IL-36 family of cytokines. Dysregulation of this balance in IL-36 signaling leads to severe chronic skin inflammation with pustules and systemic symptoms which carry significant morbidity and mortality often associated with sepsis and multi-organ failure.1 Imsidolimab inhibits the function of the IL-36R, compensating for the deficiency of the endogenous IL-36 regulator in patients with GPP. Imsidolimab has successfully concluded its development program in GPP, including the GEMINI-1 and GEMINI-2 global Phase 3 studies. In 2025, Vanda intends to initiate and complete the technology transfer activities and will immediately begin preparing the BLA and MAA applications for the US and EU and making preparations for commercialization. "We are excited to add imsidolimab to Vanda's product portfolio for rare orphan disorders, as well as explore the potential of this IL-36 signal regulator in the treatment of additional inflammatory conditions where the IL-36 homeostatic balance is dysregulated," said Mihael H. Polymeropoulos, M.D., Vanda's President, CEO and Chairman of the Board. "Imsidolimab has great synergy with our commercial portfolio, leveraging both our rare disease expertise in the US and EU as well as the anti-inflammatory portfolio that includes Ponvory® for multiple sclerosis, psoriasis and ulcerative colitis." GPP prevalence estimates in the general population vary considerably, between 1.76 and 124 patients per million persons worldwide.2 The majority of GPP cases are caused by genetic variants in IL36RN.3,4 Loss-of-function mutations in IL36RN are mostly missense mutations in a recessive pattern and result in unrestricted IL-36 activity.5,6 "GPP is a severely debilitating, life-threatening skin disease in need of novel therapeutic approaches," said Johann Gudjonsson, M.D., Ph.D., Arthur C. Curtis Professor of Molecular Skin Immunology and Scholar of the Taubman Medical Research Institute, University of Michigan. "The positive Phase 3 data, demonstrating GPP patients achieved rapid disease clearance through Week 4 after a single dose of infused imsidolimab, and maintained clear to almost clear skin for at least 24 weeks, with no clinically meaningful safety signals, represents a promising new option for patients living with this disease. I'm excited imsidolimab is progressing toward a regulatory filing this year." "Vanda is an ideal partner for imsidolimab due to their strong regulatory and commercial capabilities in the US and Europe, evidenced by successful recent launches in specialty and rare diseases, and their commitment to invest in label expansion across their therapeutic portfolio, including their growing presence in inflammatory disease," said Daniel Faga, president and chief executive officer of Anaptys. "Following our productive pre-BLA meeting with FDA in 2024, we look forward to Vanda's BLA and MAA submissions later in 2025, with the hope that this potentially differentiated therapeutic option will be made available for patients living with GPP, a burdensome, and sometimes life-threatening skin disease." Under the terms of the agreement, Vanda will make to Anaptys an upfront payment of $10 million and a $5 million payment for existing drug supply. Anaptys is also eligible to receive up to $35 million for future regulatory approval and sales milestones in addition to a 10% royalty on net sales. Vanda will receive an exclusive global license to develop, manufacture and commercialize imsidolimab. Guggenheim Securities acted as financial advisor and Fenwick & West LLP served as legal counsel to Anaptys on this transaction. Cantor Fitzgerald & Co. acted as financial advisor and Orrick, Herrington & Sutcliffe LLP served as legal counsel to Vanda. About GEMINI-1 and GEMINI-2 Studies In the 45-patient GEMINI-1 Phase 3 trial, patients were randomized 1:1:1 to receive a single infusion of 750mg intravenous (IV) imsidolimab, 300mg IV imsidolimab or placebo at Day 0. Of the patients who received a single dose of 750mg IV imsidolimab, 53% achieved a GPP Physician Global Assessment (GPPPGA) score of 0/1 (clear or almost clear skin) at Week 4 (primary endpoint), compared to 13% of the patients on placebo (p=0.0131). Of the patients who received a single dose of 300mg IV imsidolimab, 53% achieved GPPPGA 0/1 at Week 4. Sixteen GPPPGA 0/1 responder patients from GEMINI-1 were subsequently re-randomized to monthly maintenance dosing of either 200mg subcutaneous (SC) imsidolimab or placebo in the GEMINI-2 Phase 3 trial. Patients were followed for at least 24 weeks and up to a maximum of 92 weeks. Of the eight responding patients from GEMINI-1 who were re-randomized to monthly 200mg SC imsidolimab maintenance therapy, 100% maintained a GPPPGA score of 0/1 and none of them experienced a flare. Of the remaining eight responding patients from GEMINI-1 who were re-randomized to placebo, 25% maintained a GPPPGA score of 0/1 and 63% experienced a flare. Data from both trials demonstrated a consistent, favorable safety and tolerability profile with no treatment-related serious adverse events (SAEs) or SAEs leading to discontinuation reported in imsidolimab-treated patients. About Imsidolimab and GPP Imsidolimab is a fully humanized IgG4 antibody that inhibits the function of the interleukin-36-receptor, or IL-36R, that is being developed for the treatment of GPP. Regulatory and patent exclusivity is expected to extend into the late 2030s. GPP is a rare, chronic, systemic autoinflammatory disease that is potentially life-threatening, if left untreated. During a GPP flare, individuals experience the sudden eruption of painful pustules. These pustules appear over large areas of the skin, accompanied by redness, severe itchiness, and dry, cracked, or scaly skin. People with GPP may also experience more general symptoms such as fever, headache, extreme tiredness, or a burning sensation on the skin. About Vanda Pharmaceuticals, Inc. Vanda is a leading global biopharmaceutical company focused on the development and commercialization of innovative therapies to address high unmet medical needs and improve the lives of patients. For more on Vanda Pharmaceuticals Inc., please visit www.vandapharma.com and follow us on X @vandapharma. About Anaptys Anaptys is a clinical-stage biotechnology company focused on delivering innovative immunology therapeutics for autoimmune and inflammatory diseases. Its lead program, rosnilimab, a depleter and agonist targeting PD-1+ T cells, is in a Phase 2b trial for the treatment of rheumatoid arthritis and in a Phase 2 trial for the treatment of ulcerative colitis. Other antibodies in its portfolio include ANB033, an anti-CD122 antagonist, in a Phase 1 trial and ANB101, a BDCA2 modulator, soon to enter clinical development. Anaptys has also discovered multiple therapeutic antibodies licensed to GSK in a financial collaboration for immuno-oncology, including an anti-PD-1 antagonist (Jemperli (dostarlimab-gxly)) and an anti-TIM-3 antagonist (cobolimab, GSK4069889). To learn more, visit www.AnaptysBio.com or follow us on LinkedIn. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to: the anticipated timing of the preparation and submission of regulatory filings in the US and EU and the initiation and completion of technology transfer activities; Vanda's plans with respect to its commercial launch activities; the estimated prevalence of GPP; the commercial availability of imsidolimab to treat patients with GPP; the potential for Anaptys to receive any royalties or milestone payments from the Vanda license agreement; and the potential for any patent life extension for imsidolimab. Statements including words such as "plan," "intend," "continue," "expect," or "ongoing" and statements in the future tense are forward-looking statements. These forward-looking statements involve risks and uncertainties, as well as assumptions, which, if they do not fully materialize or prove incorrect, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Forward-looking statements are subject to risks and uncertainties that may cause each company's actual activities or results to differ significantly from those expressed in any forward-looking statement, including risks and uncertainties related to each company's ability to advance its product candidates, obtain regulatory approval of and ultimately commercialize each of its product candidates, the timing and results of preclinical and clinical trials, each company's ability to fund development activities and achieve development goals, each company's ability to protect intellectual property, and the accuracy of the of the estimates of the number of patients with GPP worldwide, and other risks and uncertainties described under the heading "Risk Factors" in documents each of the companies files from time to time with the Securities and Exchange Commission. These forward-looking statements speak only as of the date of this press release, and each of the companies undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date hereof. Vanda Pharmaceuticals Contact: Kevin Moran Senior Vice President, Chief Financial Officer and Treasurer 202.734.3400 pr@vandapharma.com Jim Golden / Jack Kelleher / Dan Moore Collected Strategies VANDA-CS@collectedstrategies.com Anaptys Contact: Nick Montemarano Executive Director, Investor Relations 858.732.0178 investors@anaptysbio.com References: SOURCE Vanda Pharmaceuticals Inc.

Phase 3License out/inPhase 2Clinical ResultImmunotherapy

100 Deals associated with Ponesimod

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KEGG	Wiki	ATC	Drug Bank
D11215	Ponesimod	L04AA	DB12016

R&D Status

Approved

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Indication	Country/Location	Organization	Date
Multiple sclerosis relapse	United States	Vanda Pharmaceuticals, Inc.	18 Mar 2021

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Chronic graft-versus-host disease	Phase 2	-	Actelion Pharmaceuticals US, Inc.	29 Sep 2016
Chronic large plaque psoriasis	Phase 2	-	Actelion Pharmaceuticals US, Inc.	31 Oct 2010
Multiple Sclerosis, Relapsing-Remitting	Phase 2	United States	Actelion Pharmaceuticals US, Inc.	01 Oct 2009
Multiple Sclerosis, Relapsing-Remitting	Phase 2	Australia	Actelion Pharmaceuticals US, Inc.	01 Oct 2009
Multiple Sclerosis, Relapsing-Remitting	Phase 2	Austria	Actelion Pharmaceuticals US, Inc.	01 Oct 2009
Multiple Sclerosis, Relapsing-Remitting	Phase 2	Belgium	Actelion Pharmaceuticals US, Inc.	01 Oct 2009
Multiple Sclerosis, Relapsing-Remitting	Phase 2	Bulgaria	Actelion Pharmaceuticals US, Inc.	01 Oct 2009
Multiple Sclerosis, Relapsing-Remitting	Phase 2	Canada	Actelion Pharmaceuticals US, Inc.	01 Oct 2009
Multiple Sclerosis, Relapsing-Remitting	Phase 2	Czechia	Actelion Pharmaceuticals US, Inc.	01 Oct 2009
Multiple Sclerosis, Relapsing-Remitting	Phase 2	Finland	Actelion Pharmaceuticals US, Inc.	01 Oct 2009

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03232073 (OPTIMUM-LT, CTgov)	Phase 3	Multiple sclerosis relapse	877	Ponesimod (Ponesimod 20 mg (Core and Extension Study))	eyebllcoqe(tpqulbbweu) = vmxwfwkipn oojvfyqnjx (nwzqdrjvux, reicxpvvxw - dofzzwfvhx) View more	-	21 Feb 2025
				Ponesimod+Teriflunomide (Teriflunomide 14 mg (Core) Then Ponesimod 20 mg (Extension))	eyebllcoqe(tpqulbbweu) = zhkxmxjjyz oojvfyqnjx (nwzqdrjvux, wwdmzalfgy - ohcqxsooxa) View more
NCT01093326 (CTgov)	Phase 2	Multiple Sclerosis, Relapsing-Remitting	353	Ponesimod (Ponesimod 10 Milligrams (mg))	jbvblmznjt(ifkgyqpxgp) = vsqpjxrlgk szdossouzo (emvnvhtuil, jyaosmkojk - cyuvhewlng) View more	-	01 Oct 2024
				Ponesimod (Ponesimod 20 Milligrams (mg))	jbvblmznjt(ifkgyqpxgp) = bwkxvrtpiz szdossouzo (emvnvhtuil, boznryalri - wifcbaworq) View more
ACTRIMS2023	Not Applicable	-	990	Ponesimod	yrpgqxnhrj(lamdlockzi) = one case of elective abortion due to ectopic pregnancy okkamieina (xtzzjflobh ) View more	Positive	30 May 2023
NCT02425644 \| NCT02634307 (EVOLVE-MS-1 \| OPTIMUM, Pubmed)	Phase 3	Multiple sclerosis relapse	-	Diroximel fumarate	pnrjwdabzp(rrotxmnbyu) = ylejoeobnb ldjqsydeoi (lktczdlfba )	-	08 May 2023
P6-3.007 (AAN2023)	Phase 3	Multiple sclerosis relapse	567	Ponesimod 20mg	rdieiwgwmd(lugnmwrvyo) = xipzqyyghw jdlkeneuin (cwqkktxzji, 1.30 - 2.31)	-	25 Apr 2023
				Teriflunomide	rdieiwgwmd(lugnmwrvyo) = eneaczdlhc jdlkeneuin (cwqkktxzji, 1.19 - 1.82)
AC-058B202 (AAN2023)	Phase 2	Rhabdomyosarcoma lymphocyte count	49	mRNA vaccines	mvhuqhcyny(duyghxtubc) = bnpqdbfsnj wfacnstsjp (pmpwttqcfa )	Positive	25 Apr 2023
				viral vector vaccines	mvhuqhcyny(duyghxtubc) = onqoxbwqdz wfacnstsjp (pmpwttqcfa )
NCT02425644 (OPTIMUM, ECTRIMS2022)	Phase 3	neurofilament light chain (NfL)	1,123	Ponesimod	vhngoqjzwn(qvxcoyfzge) = rdontdbzsz gdzziqvnyw (pmwwfsgmnb )	Positive	26 Oct 2022
				Teriflunomide	vhngoqjzwn(qvxcoyfzge) = hmhkqytdyc gdzziqvnyw (pmwwfsgmnb )
NCT02425644 (OPTIMUM, ECTRIMS2022)	Phase 3	Multiple sclerosis relapse	567	Ponesimod 20 mg	vwrgwqjgea(pjjjftppcp) = vkpcxdsafu ryqzaoqnfg (yinugjpuhk, 1.30 - 2.31)	-	12 Oct 2022
NCT02425644 (OPTIMUM, ECTRIMS2022)	Phase 3	Hypovolemia	-	Ponesimod	hdyzeqgvil(dxloaxgcay) = kikkmxuyzd cedezadjdc (rjyvesshjp )	-	12 Oct 2022
OPTIMUM study (ECTRIMS2022)	Not Applicable	Multiple sclerosis relapse	-	Ponesimod 20 mg	wudwpcgqjd(ozvdlkpnsk): OR = 1.9 (95% CI, 1.4 - 2.4)	Positive	12 Oct 2022
				Teriflunomide 14 mg

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