S1PR1 modulators(Sphingosine 1-phosphate receptor Edg-1 modulators), S1PR5 modulators(Sphingosine 1-phosphate receptor Edg-8 modulators), S1PRs modulators(Sphingosine 1-phosphate receptor modulators)

Therapeutic Areas

Immune System DiseasesNervous System DiseasesOther Diseases

Active Indication

Multiple Sclerosis, Secondary ProgressiveMultiple SclerosisAlzheimer Disease+ [1]

Inactive Indication

Cerebral HemorrhageDermatomyositisHemorrhagic stroke+ [5]

Originator Organization

Novartis Pharma AG

Active Organization

Novartis Pharmaceuticals Corp.

Novartis AGNovartis Europharm Ltd.

+ [4]

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

United States (26 Mar 2019),

Multiple Sclerosis

RegulationSpecial Review Project (China), Orphan Drug (United States), Priority Review (China)

Structure/Sequence

Molecular FormulaC33H39F3N2O7

InChIKeyGDOJWCQYEGMSSF-FLNKEUCSSA-N

CAS Registry1234627-85-0

Clinical Trials associated with Siponimod Fumaric Acid

NCT06639282

/ Not yet recruitingPhase 2IIT

SIPO1-AD: a Phase II Clinical Trial for the Assessment of Safety, Tolerability, and Efficacy of Siponimod in Patients with Mild Alzheimer&#39;s Disease Dementia

Collaboration with multiple sclerosis (MS) specialty colleagues led us to formulate the central hypothesis that Siponimod could lower the rate of brain atrophy in Alzheimer's disease (AD) subjects. To test our central hypothesis, we will carry out an 18-month Phase II, double-blind, randomized, twoarmed, placebo controlled, proof-of-concept clinical study in early AD subjects (i.e. mild AD) who will be receiving an escalating dose of Siponimod or placebo in the ratio 2:1 for 12 months, followed by a 6-month washout period. The primary outcome measures are safety and tolerability of Siponimod in mild AD subjects. The secondary outcome measures are the rates of brain atrophy derived from volumetric MRI (vMRI) as a proxy for neurodegeneration conducted at baseline, 6, 12, and 18 months. The tertiary outcome measures are the changes in cognition and the levels of AD-associated (e.g., Aβ and tau) and inflammatory biomarkers in CSF after Siponimod exposure. In an exploratory effort, we will also measure plasma inflammatory markers during the entire duration of the study to investigate whether one or more of these markers can be used as dynamic surrogate markers of treatment response. Using our unique experience with the repurposing of immunomodulatory drugs for AD (and NCT #04032626), in the present project we are using elements of clinical trial design that we believe were successful and made some adjustments to fit the pharmacologic and toxic properties of Siponimod.

Start Date01 Nov 2024

Sponsor / Collaborator

St. Joseph's Medical Center, Inc.

[+5]

CTR20232992

/ CompletedNot Applicable

西尼莫德片的人体生物等效性研究

[Translation] Study on the bioequivalence of siponimod tablets in healthy volunteers

研究空腹/餐后状态下单次口服受试制剂西尼莫德片与参比制剂西尼莫德片（万立能®）在健康成年受试者体内的药代动力学，评价空腹/餐后状态下口服两种制剂的生物等效性和安全性。

[Translation]

The pharmacokinetics of a single oral dose of the test preparation Siponimod tablets and the reference preparation Siponimod tablets (Vanlin®) in healthy adult subjects were studied in the fasting/postprandial state, and the bioequivalence and safety of the two preparations were evaluated in the fasting/postprandial state.

Start Date23 Sep 2023

Sponsor / Collaborator

Qilu Pharmaceutical Co., Ltd.

CTR20230278

/ CompletedPhase 4

一项在中国复发型多发性硬化患者中评价BAF312的有效性和安全性的回顾性、多中心真实世界研究。

[Translation] A retrospective, multicenter, real-world study evaluating the efficacy and safety of BAF312 in Chinese patients with relapsing multiple sclerosis.

1.在中国真实世界人群中，基于年复发率描述BAF312在复发型多发性硬化(RMS)患者中的有效性。 2.描述开始BAF312治疗后12个月时保持无复发的患者比例。 3.在中国真实世界人群中描述BAF312在RMS患者中的安全性特征。 4.描述开始BAF312治疗后12个月时无MRI活动性的患者比例。

[Translation]

1. Describe the efficacy of BAF312 in patients with relapsing multiple sclerosis (RMS) based on annualized relapse rate in a real-world Chinese population. 2. Describe the proportion of patients who remain relapse-free at 12 months after starting BAF312 treatment. 3. Describe the safety profile of BAF312 in patients with RMS in a real-world Chinese population. 4. Describe the proportion of patients with no MRI activity at 12 months after starting BAF312 treatment.

Start Date23 Apr 2023

Sponsor / Collaborator

Novartis Farmacéutica SA

[+3]

100 Clinical Results associated with Siponimod Fumaric Acid

100 Translational Medicine associated with Siponimod Fumaric Acid

100 Patents (Medical) associated with Siponimod Fumaric Acid

368

Literatures (Medical) associated with Siponimod Fumaric Acid

01 Feb 2025·Multiple Sclerosis and Related Disorders

Effect of siponimod on retinal thickness, a marker of neurodegeneration, in participants with SPMS: Findings from the EXPAND OCT substudy

Article

Author: Vermersch, Patrick ; Li, Bingbing ; Mousseau, Marie-Catherine ; Maio-Twofoot, Tina ; Paul, Friedemann ; Shi, Xiaofang ; Bar-Or, Amit ; Giovannoni, Gavin ; Cree, Bruce A C ; Wolf, Sebastian ; Fox, Robert J ; Gold, Ralf ; Kappos, Ludwig

BACKGROUNDPeople with MS show abnormal thinning of the retinal layers, which is associated with clinical disability and brain atrophy, and is a potential surrogate marker of neurodegeneration and treatment effects.OBJECTIVETo evaluate the utility of retinal thickness as a surrogate marker of neurodegeneration and treatment effect in participants with secondary progressive MS (SPMS) from the optical coherence tomography (OCT) substudy of the EXPAND Phase 3 clinical trial (siponimod versus placebo).METHODSIn the OCT substudy population (n = 159), treatment effects on change in the average thickness of the retinal layer, peripapillary retinal nerve fiber layer (pRNFL), and combined macular ganglion cell and inner plexiform layers (GCIPL) were analyzed by high-definition spectral domain OCT at months 3, 12, and 24.RESULTSThinning from baseline was observed across all retinal layers and time points in the placebo group. Siponimod significantly reduced GCIPL thinning versus placebo at month 24 (adjusted mean [SE] [µm]: -0.47 [0.81] vs. -4.29 [1.23]; p = 0.01), and overall retinal thinning at months 12 (+0.66 [0.54] vs. -1.86 [0.75]; p = 0.006) and 24 (-0.05 [0.59] vs. -2.30 [0.88]; p = 0.033). Although not significant, results for pRNFL consistently followed the same trends.CONCLUSIONThis exploratory substudy supports further investigation of OCT measurement of retinal atrophy as a non-invasive potential biomarker of treatment effects on neurodegeneration in SPMS.

01 Feb 2025·Multiple Sclerosis and Related Disorders

Efficacy and safety of disease-modifying therapies in pediatric-onset multiple sclerosis: A systematic review of clinical trials and observational studies

Review

Author: Śladowska, Katarzyna ; Brzostek, Tomasz ; Moćko, Paweł ; Kawalec, Paweł

OBJECTIVEThis study aimed to review the efficacy and safety profile of disease-modifying therapies (DMTs) in patients with relapsing pediatric-onset multiple sclerosis (POMS).METHODSA systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Published randomized controlled trials (RCTs), nonrandomized studies with a control group, large single-arm studies, and ongoing (unpublished) studies investigating the use of approved and unapproved DMTs in POMS were included. Eligible published studies were identified in MEDLINE (via PubMed), EMBASE, and the Cochrane Library, and unpublished studies were identified in a clinical trials registry (www.CLINICALTRIALSgov).RESULTSA total of 13 published studies were included in the systematic review: 4 RCTs, 3 observational studies with a control group, and 6 large single-arm studies. The following DMTs for the treatment of POMS were evaluated in the included studies: interferon beta-1a, interferon beta-1b, teriflunomide, dimethyl fumarate, fingolimod, natalizumab, glatiramer acetate, and ocrelizumab. All DMTs were shown to be effective in reducing relapse rates, preventing disability progression, and reducing disease activity in MRI in patients with POMS. DMTs that are considered highly effective in adults with multiple sclerosis (natalizumab, fingolimod) were also shown to be more effective than interferon beta-1a in POMS. A total of 9 ongoing (unpublished) studies were identified, including 5 RCTs. The following drugs were evaluated: ozanimod, fingolimod, peginterferon beta-1a, ocrelizumab, ofatumumab, siponimod, alemtuzumab, and natalizumab.CONCLUSIONThe number of DMTs approved for the treatment of POMS is limited, and some of the available DMTs are used off-label. The available evidence from published studies of varying reliability supports the efficacy of DMTs in POMS. However, well-designed, long-term RCTs in the pediatric population are needed. The results of ongoing studies may fill the existing gap in clinical evidence, possibly leading to the approval of more highly effective DMTs for patients with POMS.

01 Feb 2025·Neuroscience Research

Siponimod inhibits microglial inflammasome activation

Article

Author: Doi, Hiroshi ; Takeuchi, Hideyuki ; Takahashi, Keita ; Tanaka, Fumiaki ; Kunii, Misako ; Ogawa, Yuki ; Hashiguchi, Shunta ; Tada, Mikiko ; Ogasawara, Akihiro ; Tanaka, Kenichi ; Komiya, Hiroyasu ; Kubota, Shun

Siponimod is the first oral drug approved for active secondary progressive multiple sclerosis. It acts as a functional antagonist of sphingosine-1-phosphate (S1P) receptor 1 (S1P₁) through S1P₁ internalization, and also serves an agonist of S1P₅; however, the detailed mechanisms of its therapeutic effects on glial cells have yet to be elucidated. In this study, we investigated the anti-inflammatory mechanism of siponimod in microglia. Pretreatment with either siponimod or the S1P₁ antagonist W146 significantly suppressed the production of interleukin-1β in activated microglia stimulated with lipopolysaccharide plus nigericin, an inflammasome activator. Furthermore, siponimod treatment reduced the protein levels of cleaved caspase-1 and inhibited the formation of aggregates of apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC specks) in microglia. Our data indicate that siponimod achieves its anti-inflammatory effects by inhibiting inflammasome activation in microglia via S1P₁ antagonism. This process is inferred to play a crucial role in mitigating the secondary progression of multiple sclerosis, where microglial activation in the gray matter is considered a key pathological factor.

News (Medical) associated with Siponimod Fumaric Acid

21 Jan 2025

·www.globenewswire.com

Pharming to nominate biopharmaceutical leader Fabrice Chouraqui as new Executive Director and Chief Executive Officer

Leiden, the Netherlands, January 21, 2025: Pharming Group N.V. (“Pharming” or “the Company”) (EURONEXT Amsterdam: PHARM/Nasdaq: PHAR) announces today that the Board of Directors has nominated Fabrice Chouraqui to become Pharming’s new Executive Director and Chief Executive Officer, succeeding Sijmen de Vries. Pharming will nominate Mr. Chouraqui for the appointment as Executive Director and Chief Executive Officer for a term of four years at an upcoming Extraordinary General Meeting of Shareholders (EGM). Information regarding the EGM, including the notice to convene, will be shared shortly in a separate press release. Upon the appointment of Mr. Chouraqui, Sijmen de Vries will resign from the Board of Directors. To ensure a smooth hand-over of tasks and responsibilities, Mr. de Vries will remain a strategic advisor to the new CEO until December 31, 2025. Dr. Richard Peters, Chairman of the Board of Directors, commented:“After an extensive search, the Board and I are confident that Fabrice Chouraqui is the right candidate to lead Pharming and continue to implement our growth strategy, shaping Pharming into the rare disease company of choice. Fabrice is a deeply experienced global pharmaceutical and biotechnology executive, who brings a wealth of profound global expertise and experience, across the entire biopharmaceutical value chain, to Pharming. On behalf of the entire Board of Directors, I would like to thank Sijmen de Vries for his great commitment to Pharming over the past 16 years and for creating the company that it is today, serving patients and paving the way for delivery on the company’s strategy for growth. We are grateful that Sijmen will continue to be available through the end of the year to ensure a smooth hand-over with Fabrice.” Sijmen de Vries, Chief Executive Officer, commented:“I am very pleased with the nomination of Fabrice Chouraqui as my successor. Fabrice brings strong leadership experience with global pharmaceutical companies and highly innovative biotechnology companies to Pharming. To make way for Fabrice to take over the executive leadership of the Company, I will resign from the Board of Directors upon the appointment of Fabrice by our shareholders. I look forward to supporting Fabrice, working closely together through the remainder of the year, and ensuring a smooth hand-over.” Fabrice Chouraqui commented:“I am honored to have the opportunity to take over the leadership of Pharming, building on the strong foundation and joining at a time when I can help propel the company through its next stage of growth in the rare disease space. I am impressed by Pharming’s growing portfolio of products and commercial opportunities which will pave the way for us to become the rare disease company of choice.” ProfileMr. Fabrice Chouraqui (date of birth: August 1, 1970, French national, U.S. citizen) is a global pharmaceutical executive with a record of value creation at Flagship Pioneering, Novartis and Bristol-Myers Squibb. A purpose-driven leader with a passion for bringing innovative treatments to patients, Mr. Chouraqui has a reputation for building strong followership in organizations. He is scientifically minded, with a deep understanding across the business spectrum, from research and development to access and commercialization, including strong expertise in investor management and business development. Across his career, Mr. Chouraqui has led the launch of treatments in many therapeutic areas, including highly targeted specialty care drugs and large primary care medicines. He consistently demonstrates strategic and innovative thinking to achieve long-lasting results and has a strong record of developing next generation talents and highly diverse teams. Until recently, Mr. Chouraqui was a CEO-Partner at Flagship Pioneering, one of the largest Biotech Venture Capital firms in the US. Mr. Chouraqui also served as CEO of Cellarity, Inc., one of the companies created by Flagship Pioneering. In his CEO capacity, Mr. Chouraqui was leading the development of Cellarity, a company which is driving a radically new approach to drug discovery by working at the intersection of AI and biology. Mr. Chouraqui raised over $250M and attracted world-renowned investors. He initiated a collaboration with Novo Nordisk and had Cellarity recognized as a top biotech to watch by several sources. Today, Mr. Chouraqui holds the position of Executive Chairman at Cellarity. Prior to joining Flagship Pioneering, Mr. Chouraqui spent 10 years at Novartis. He was President of Novartis Pharmaceuticals USA from 2016 to 2019, during which he delivered strong growth despite negative price impact and significantly improved profitability. Promoted to turn around performance after the business suffered issues with recent launches, Mr. Chouraqui developed sophisticated commercial and access capabilities to meet the new market environment. He achieved strong market positions for two significant growth drivers (Cosentyx and Entresto), drove the uptake of the rare disease drug Ilaris, initiated the landmark PIONEER clinical trial in heart failure, and championed several business development initiatives. Mr. Chouraqui moved the organization’s culture from “consensus building, conservative and siloed” to “questioning, experimenting and collaborative.” He also served as Novartis representative on the board of BIO. Before leading the US organization, Mr. Chouraqui was President, Latin America & Canada (2014-2016) for Novartis Pharmaceuticals, responsible for leading a portfolio shift from established primary care medicines to innovative specialty care drugs. He also served as Global Head, Business Franchise Neuroscience (2012-2014). In this role, he relaunched Gilenya (Multiple Sclerosis) following a post-launch regulatory review and made Gilenya the largest growth contributor in the Novartis five-year strategic plan. Mr. Chouraqui also addressed late-stage pipeline gaps with the start of the siponimod program in Secondary Progressive Multiple Sclerosis (approved in 2019) and the identification of business development opportunities, which led to the in-licensing of ofatumumab in MS from GSK (launched as Kesimpta) and a partnership with Amgen on erenumab for migraine (launched as Aymovig). From 2000 to 2010, Mr. Chouraqui held multiple international roles at Bristol-Myers Squibb, ultimately serving as Vice President, Commercial Operations, Asia-Pacific and General Manager, Southeast Asia (2008-2010). He began his career in R&D roles at Roussel Uclaf and Hoechst Marion Roussel, pharmaceutical companies that were predecessors to today’s Sanofi. Mr. Chouraqui earned a MBA from INSEAD and a Doctorate in Pharmacy, a Post-Graduate Degree in Quality Assurance of Medicines, and a MSc in Biological and Medicinal Sciences from University of Paris V. Mr. Chouraqui shall have stepped down as Executive Chairman of Cellarity, Inc., a non-listed company, no later than upon his appointment as the new Executive Director and Chief Executive Officer of Pharming. Thereafter, Mr. Chouraqui intends to serve as a non-executive Board member of Cellarity. Mr. Chouraqui also holds the position of independent Board member of OranoMed, a non-listed (and therefore private) subsidiary of Orano Group. OranoMed is a company specialized in the research and development of Pb-212 based radioligand alpha therapies for the treatment of various types of cancers. The resume of Mr. Chouraqui is available on our website. For further public information, contact:Pharming Group, Leiden, the NetherlandsMichael Levitan, VP Investor Relations & Corporate CommunicationsT: +1 (908) 705 1696E: investor@pharming.com FTI Consulting, London, UKVictoria Foster Mitchell/Alex Shaw/Amy ByrneT: +44 203 727 1000 LifeSpring Life Sciences Communication, Amsterdam, the NetherlandsLeon MelensT: +31 6 53 81 64 27E: pharming@lifespring.nl About Pharming Group N.V. Pharming Group N.V. (EURONEXT Amsterdam: PHARM/Nasdaq: PHAR) is a global biopharmaceutical company dedicated to transforming the lives of patients with rare, debilitating, and life-threatening diseases. Pharming is commercializing and developing an innovative portfolio of protein replacement therapies and precision medicines, including small molecules and biologics. Pharming is headquartered in Leiden, the Netherlands, and has employees around the globe who serve patients in over 30 markets in North America, Europe, the Middle East, Africa, and Asia-Pacific. For more information, visit www.pharming.com and find us on LinkedIn. Forward-Looking Statements   This press release may contain forward-looking statements. Forward-looking statements are statements of future expectations that are based on management’s current expectations and assumptions and involve known and unknown risks and uncertainties that could cause actual results, performance, or events to differ materially from those expressed or implied in these statements. These forward-looking statements are identified by their use of terms and phrases such as “aim”, “ambition”, ‘‘anticipate’’, ‘‘believe’’, ‘‘could’’, ‘‘estimate’’, ‘‘expect’’, ‘‘goals’’, ‘‘intend’’, ‘‘may’’, “milestones”, ‘‘objectives’’, ‘‘outlook’’, ‘‘plan’’, ‘‘probably’’, ‘‘project’’, ‘‘risks’’, “schedule”, ‘‘seek’’, ‘‘should’’, ‘‘target’’, ‘‘will’’ and similar terms and phrases. Examples of forward-looking statements may include statements with respect to timing and progress of Pharming's preclinical studies and clinical trials of its product candidates, Pharming's clinical and commercial prospects, and Pharming's expectations regarding its projected working capital requirements and cash resources, which statements are subject to a number of risks, uncertainties and assumptions, including, but not limited to the scope, progress and expansion of Pharming's clinical trials and ramifications for the cost thereof; and clinical, scientific, regulatory, commercial, competitive and technical developments. In light of these risks and uncertainties, and other risks and uncertainties that are described in Pharming's 2023 Annual Report and the Annual Report on Form 20-F for the year ended December 31, 2023, filed with the U.S. Securities and Exchange Commission, the events and circumstances discussed in such forward-looking statements may not occur, and Pharming's actual results could differ materially and adversely from those anticipated or implied thereby. All forward-looking statements contained in this press release are expressly qualified in their entirety by the cautionary statements contained or referred to in this section. Readers should not place undue reliance on forward-looking statements. Any forward-looking statements speak only as of the date of this press release and are based on information available to Pharming as of the date of this release. Pharming does not undertake any obligation to publicly update or revise any forward-looking statement as a result of new information, future events or other information. Inside InformationThis press release relates to the disclosure of information that qualifies, or may have qualified, as inside information within the meaning of Article 7(1) of the EU Market Abuse Regulation. Attachments Fabrice Chouraqui Pharming to nominate new Executive Director and Chief Executive Officer_EN_21JAN25

Executive ChangeDrug Approval

11 Dec 2024

·www.businesswire.com

Genesis Therapeutics Expands Leadership Team with Appointments of Chief Scientific Officer, SVP of Engineering, and Board Chairman

BURLINGAME, Calif.--( BUSINESS WIRE )-- Genesis Therapeutics , a company pioneering artificial intelligence (AI) technologies to create breakthrough medicines for patients, today announced the appointments of three key members during 2024 to its senior leadership team and Board of Directors: Shifeng Pan, Ph.D., as Chief Scientific Officer; Alla Ivanova as Senior Vice President of Engineering; and Paul A. Friedman, M.D., as Chairman of the Board. “ We are thrilled to welcome to our team these exceptional leaders who share belief in our mission and approach to transforming drug discovery with groundbreaking predictive and generative AI technologies,” said Evan Feinberg, Ph.D., founder and CEO of Genesis. “ Their industrial expertise across technology and drug discovery will enable us to further advance our GEMS (Genesis Exploration of Molecular Space) AI platform, expand our therapeutic pipeline, and ultimately create breakthrough treatments for patients suffering from severe diseases.” Shifeng Pan, Ph.D., Chief Scientific Officer: Dr. Pan joined Genesis in April 2024 and oversees R&D activities for Genesis’ pipeline of AI-enabled therapeutics. He brings more than two decades of experience in medicinal chemistry and biopharmaceutical research, including a 22-year career at Novartis, where he served as Head of Discovery Chemistry at the Genomics Institute of the Novartis Research Foundation. At Novartis, he led the discovery of FDA-approved drugs ODOMZO ® , BRAFTOVI ® , and MAYZENT ® , as well as numerous other programs across several therapeutic areas. Dr. Pan joins Genesis from Odyssey Therapeutics, where he was Executive Vice President and Head of Discovery. He earned a doctorate in organic chemistry from New York University. “ Genesis’ AI capabilities enable the discovery of novel and breakthrough molecules, making its platform well-suited to address challenging or historically undruggable targets,” said Dr. Pan. “ It’s an exciting time for the field of AI-enabled drug discovery and our premier team of engineers, chemists, and biologists who are leveraging the GEMS platform to rapidly advance our broad therapeutic pipeline.” Alla Ivanova, Senior Vice President of Engineering: Ms. Ivanova joined Genesis in November 2024 and brings over 25 years of experience driving innovation in software development; spanning data center management, large-scale infrastructure, and high-traffic web applications to cutting-edge AI/ML solutions. She has held executive leadership roles at notable tech companies including Head of Looker Engineering at Google Cloud, VP of Cloud & Data Infrastructure at Atlassian, Head of Core Infrastructure at Uber, Senior Director of Data Platform at Groupon, and Software Engineering Manager at Netflix. Ms. Ivanova earned her master's degree in applied mathematics and computer science from Kazan Federal University. “ At a time when AI is redefining the boundaries of what’s possible in drug discovery, I’m honored to be joining the Genesis team,” said Ms. Ivanova. “ The company’s AI platform, GEMS, has the potential to unlock the promise of computational drug design and discover life-changing medicines for patients. I’m excited to continue advancing transformational AI work, not just for innovation’s sake but to make a meaningful difference in human health – a mission that resonates deeply with me and the future I envision for AI.” Paul A. Friedman, M.D., Chairman of the Board of Directors: Dr. Friedman has served as Chairman of the company’s Board of Directors since April 2024. With decades of experience in biotechnology and drug development, he has held senior leadership roles at notable pharmaceutical companies, including CEO of Madrigal Pharmaceuticals (2016–2023), CEO of Incyte (2001–2014), President of Research and Development at DuPont-Merck Pharmaceutical, President of DuPont Pharmaceuticals Research Laboratories, and Senior Vice President of Merck Research Laboratories. He has also served as a board member for several publicly held pharmaceutical companies, including Incyte and Alexion. A diplomate of the American Board of Internal Medicine and member of the American Society of Clinical Investigation, Dr. Friedman earned his medical degree from Harvard Medical School. " Genesis is in an exciting period of growth following an outstanding Series B fundraise last year and recent collaboration with Gilead, positioning the company well to advance and expand its AI-enabled pipeline to develop breakthrough therapies for patients,” said Dr. Friedman. This expansion of Genesis’ senior leadership team follows the company’s appointments of two industry veterans to its Board of Directors: Vijay Pande, Ph.D., Founding General Partner at Andreessen Horowitz’s (a16z) Bio + Health fund, joined as a Director in 2023, and Mohamed “Sid” Siddeek, Vice President and Head of NVentures, NVIDIA’s venture capital arm, joined as an observer in 2024. About Genesis Therapeutics Genesis Therapeutics is pioneering AI for biotechnology by leveraging its generative and predictive AI platform called GEMS (Genesis Exploration of Molecular Space) for small molecule drug discovery. GEMS synthesizes proprietary AI methods, including language models, diffusion models, and physical ML simulations, to generate and optimize molecules for complex targets. Genesis has raised over $300 million from leading life science, tech, and AI-focused investors, and is building a therapeutic pipeline for a variety of high-impact targets. Genesis is headquartered in Burlingame, CA, with a fully integrated laboratory in San Diego. For more information on Genesis, please visit the company’s website at www.genesistherapeutics.ai .

Executive Change

07 Dec 2023

·www.prnewswire.com

Vanda Pharmaceuticals Acquires U.S. and Canadian Rights to PONVORY® (ponesimod), a Selective S1P1R Modulator Approved for Patients with Relapsing Multiple Sclerosis

WASHINGTON, Dec. 7, 2023 /PRNewswire/ -- Vanda Pharmaceuticals Inc. (Vanda) (Nasdaq: VNDA) today announced that it has acquired U.S. and Canadian rights to PONVORY® (ponesimod) from Actelion Pharmaceuticals Ltd. (Janssen), a Johnson & Johnson Company. PONVORY® is approved by the U.S. Food and Drug Administration (FDA) and Health Canada to treat adults with relapsing forms of multiple sclerosis (RMS), to include clinically isolated syndrome, relapsing-remitting disease and active secondary progressive disease. PONVORY® has a proven safety profile with over 10 years of data. "The acquisition of Ponvory is a significant milestone for Vanda, as it expands our commercial portfolio and gives us access to a versatile immune response modifier that can potentially have broad application in treating a number of autoimmune-based disorders," said Mihael H. Polymeropoulos, M.D., Vanda's President, CEO and Chairman of the Board. In a clinical study, PONVORY® was shown to be superior to Aubagio®, another approved drug for multiple sclerosis (MS), in the annual rate of relapse and it was also associated with fewer T2 and T1 MRI lesions versus the comparator. Approximately 9 out of 10 people taking PONVORY® did not experience disability progression over 2 years (as measured by the time to 3-month Confirmed Disability Progression).1 The effect of PONVORY® on the decrease of circulating lymphocytes is reversible so lymphocytes quickly return to baseline levels after discontinuation of PONVORY®. This rapid reversible effect is important for people needing to pause therapy for a vaccine. For women of childbearing age who want to become pregnant, PONVORY® is eliminated from the body in about 7 days after stopping treatment. The mechanism of action of PONVORY® makes it also a potential therapeutic candidate for the treatment of a diverse group of inflammatory/autoimmune disorders ranging from psoriasis to ulcerative colitis. In a randomized placebo controlled clinical study, PONVORY® has also been shown to reduce the symptoms and signs of psoriasis.2 Under the terms of the agreement, Vanda paid $100 million to acquire the U.S. and Canadian rights to PONVORY®. Janssen will continue to operate the business pursuant to a Transitional Business License Agreement, during which time, Vanda and Janssen will transition regulatory and supply responsibility for PONVORY® to Vanda. Stifel acted as exclusive financial advisor to Vanda with respect to this acquisition. About PONVORY® PONVORY® (ponesimod) is a daily oral selective sphingosine-1-phosphate receptor 1 (S1P1R) modulator, indicated to treat adults with relapsing forms of MS, to include clinically isolated syndrome, relapsing-remitting disease and active secondary progressive disease. PONVORY® blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood. PONVORY® does not require genetic testing or first-dose cardiac monitoring for most patients. Because initiation of PONVORY® treatment results in a decrease in heart rate, first-dose monitoring is recommended in patients with certain preexisting cardiac conditions. For full U.S. Prescribing Information for PONVORY®, including Important Safety Information, visit . The PONVORY® Orange Book listed patent with the latest expiry date is set to expire in December 2035. About Multiple Sclerosis MS is a chronic autoimmune inflammatory disease of the central nervous system (CNS) in which immune cells attack myelin (the protective casing that insulates nerve cells), damaging or destroying it and causing inflammation. This affects how the CNS processes information and communicates with the rest of the body, causing the neurologic signs and symptoms of MS. Symptoms vary by person, but common symptoms include fatigue, balance and walking problems, numbness or tingling, dizziness and vertigo, vision problems, bladder and bowel problems and weakness. About Sphingosine-1-Phosphate Receptor 1 Modulators PONVORY® (ponesimod) belongs in the molecular class of sphingosine-1-phosphate (S1P) analogs that act as modulators of the S1P receptor (S1PR). There are five S1PR (1-5) subtypes with different tissue distribution and functional specificity. PONVORY® is a selective ligand for the S1P1R subtype. It has been speculated that selectivity for S1P1R, rapid onset and reversibility of pharmacological effects, and an optimized titration regimen may differentiate ponesimod from fingolimod, the first of the oral S1PR modulators in the treatment of multiple sclerosis, and may lead to better safety and tolerability.3 Besides fingolimod (FDA approved in 2010), there are four additional FDA-approved members in the S1P modulator class that include siponimod (2019), ozanimod (2020), ponesimod (2021) and etrasimod (2023). With the exception of etrasimod, all other drugs are currently approved for the treatment of MS. Ozanimod and etrasimod are approved for the treatment of ulcerative colitis. The S1PR modulators act by preventing the egress of lymphocytes from the lymph nodes and as such reduce the number of circulating lymphocytes leading to a decrease of the autoimmune response at the target site. Based on the latest Datamonitor market forecasts for multiple sclerosis and ulcerative colitis, the S1P market in the U.S. is expected to be approximately $2 billion in 2024 and to grow to approximately $3.5 billion in 2028.4 References Kappos L., Fox RJ., Burcklen M. (2021). Ponesimod Compared With Teriflunomide in Patients With Relapsing Multiple Sclerosis in the Active-Comparator Phase 3 OPTIMUM Study: A Randomized Clinical Trial. JAMA neurology, 78(5), 558–567. Vaclavkova, A., Chimenti, S., Arenberger, P., Holló, P., Sator, P. G., Burcklen, M., Stefani, M., & D'Ambrosio, D. (2014). Oral ponesimod in patients with chronic plaque psoriasis: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet (London, England), 384(9959), 2036–2045. (14)60803-5 D'Ambrosio, D., Freedman, M. S., & Prinz, J. (2016). Ponesimod, a selective S1P1 receptor modulator: a potential treatment for multiple sclerosis and other immune-mediated diseases. Therapeutic advances in chronic disease, 7(1), 18–33. Datamonitor Healthcare – Multiple Sclerosis (MS) Patient-Based Market Forecast published October 2023 and Datamonitor Healthcare – Ulcerative Colitis Patient-Based Market Forecast published March 2023. 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 statements regarding the impact that the acquisition of PONVORY® will have on Vanda's commercial portfolio, the potential of PONVORY® to treat a diverse group of inflammatory/autoimmune disorders, the post-closing transitional plans to operate the U.S. and Canadian PONVORY® business during the transition period, the parties' plans to transition regulatory and supply responsibility for PONVORY® to Vanda, the duration of the patent protection for PONVORY®, the potential differentiation of PONVORY® from other drugs in its class, the safety and tolerability of PONVORY®, and the size and growth of the potential U.S. market for the class of S1P1R modulators 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 successfully commercialize PONVORY®, the results of any clinical trials conducted for PONVORY® in the treatment of other inflammatory/autoimmune disorders and Vanda's ability to obtain regulatory approval of PONVORY® for any such additional indications, the seller's ability to effectively operate the U.S. and Canadian PONVORY® business during the transition period, the parties' ability to transition regulatory and supply responsibility for PONVORY® to Vanda, the ability of the parties to successfully defend any challenge to the PONVORY® patents, the ability of the identified characteristics of PONVORY® and an optimized titration regimen to differentiate it from other drugs in its class and result in better safety and tolerability, and the market acceptance and commercial success of S1P1R modulators. 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 Current Report on Form 8-K 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. Vanda Corporate Contact: Kevin Moran Senior Vice President, Chief Financial Officer and Treasurer Vanda Pharmaceuticals Inc. 202-734-3400 [email protected] SOURCE Vanda Pharmaceuticals Inc.

Drug ApprovalAcquisitionPhase 3Phase 2License out/in

100 Deals associated with Siponimod Fumaric Acid

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KEGG	Wiki	ATC	Drug Bank
-	Siponimod Fumaric Acid	L04AA42	DB12371

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Multiple Sclerosis, Secondary Progressive	Liechtenstein	Novartis Europharm Ltd.	13 Jan 2020
Multiple Sclerosis, Secondary Progressive	European Union	Novartis Europharm Ltd.	13 Jan 2020
Multiple Sclerosis, Secondary Progressive	Iceland	Novartis Europharm Ltd.	13 Jan 2020
Multiple Sclerosis, Secondary Progressive	Norway	Novartis Europharm Ltd.	13 Jan 2020
Multiple Sclerosis	United States	Novartis Pharmaceuticals Corp.	26 Mar 2019

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Multiple Sclerosis, Secondary Progressive	Phase 3	Russia	Novartis Pharmaceuticals Corp.	20 Dec 2012
Multiple Sclerosis, Secondary Progressive	Phase 3	Japan	Novartis Pharmaceuticals Corp.	20 Dec 2012
Multiple Sclerosis, Secondary Progressive	Phase 3	United States	Novartis Pharmaceuticals Corp.	20 Dec 2012
Multiple Sclerosis, Secondary Progressive	Phase 3	Argentina	Novartis Pharmaceuticals Corp.	20 Dec 2012
Multiple Sclerosis, Secondary Progressive	Phase 3	Turkey	Novartis Pharmaceuticals Corp.	20 Dec 2012
Multiple Sclerosis, Secondary Progressive	Phase 3	China	Novartis Pharmaceuticals Corp.	20 Dec 2012
Multiple Sclerosis, Secondary Progressive	Phase 3	Switzerland	Novartis Pharmaceuticals Corp.	20 Dec 2012
Multiple Sclerosis, Secondary Progressive	Phase 3	Israel	Novartis Pharmaceuticals Corp.	20 Dec 2012
Multiple Sclerosis, Secondary Progressive	Phase 3	Australia	Novartis Pharmaceuticals Corp.	20 Dec 2012
Multiple sclerosis relapse	Discovery	United States	Novartis Pharmaceuticals Corp.	14 Feb 2019

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04792567 (AMA-VACC, CTgov)	Phase 4	Multiple Sclerosis, Secondary Progressive	41	BAF312+BNT162+mRNA-1273 (Siponimod - Continuous)	zlctxttqgc(yrmkccqcmm) = degadncllg ikmairliiw (ywjtkcizdq, ikpyfhjapq - djlkajnhvl) View more	-	17 May 2024
				BAF312+BNT162+mRNA-1273 (Siponimod- Interrupted)	zlctxttqgc(yrmkccqcmm) = yffmohwlze ikmairliiw (ywjtkcizdq, bqktxdqzaa - rpaqrcyhbi) View more
ECTRIMS2023	Not Applicable	Multiple Sclerosis	67	Siponimod	ruxjciuocn(lvoodhjccr) = khaxugslzo aolmlrzjsy (itxuwenazy )	-	01 Oct 2023
EAN2023	Not Applicable	Multiple Sclerosis, Secondary Progressive	-	Siponimod	dekvtbrrmq(rkftjdekun) = uhqdaxlijq nvlojeqidq (barwkhpwmq )	-	28 Jun 2023
ACTRIMS2023	Not Applicable	Multiple Sclerosis, Secondary Progressive Second line	29	Siponimod	(pvcqovxaay) = 4 patients discontinued treatment due to adverse events and one by personal decision. 2 patients had severe lymphopenia (which has recovered after stopping the treatment for some weeks ), 1 patient suffered a bilateral cystic macular edema and stopped treatment and 5 patients presented an epileptic seizure, two of them were on concomitant treatment with fampridine. Three of them have discontinued the treatment. No alterations in liver enzymes have been observed. No documented increase in frequent infections. ygnrpxaslc (xqyfgnaupz ) View more	Positive	30 May 2023
ECTRIMS2022	Not Applicable	COVID-19	-	Fingolimod	usmujbaneg(ctcupvppvn) = liczdijwzv epiqugxrqn (ipppyrtolz ) View more	-	12 Oct 2022
				Siponimod	usmujbaneg(ctcupvppvn) = uwbkxzfugy epiqugxrqn (ipppyrtolz ) View more
ECTRIMS2022	Not Applicable	Multiple Sclerosis, Secondary Progressive CYP2C9 genotype	-	Siponimod 2mg	qrnyuelldc(calfxuquut) = A total of 90 patients discontinued the study; 48 prior to and 42 after siponimod exposure ykyyfkhbko (ltxmddlzmm )	-	12 Oct 2022
				Siponimod 1mg
EAN2022	Not Applicable	Multiple Sclerosis, Secondary Progressive	-	Siponimod	czflszgqov(idpsdavlsu) = cbxtrnxbce eghrycwmji (ajixmvsufl )	-	24 Jun 2022
				Placebo	czflszgqov(idpsdavlsu) = tyawxypuzm eghrycwmji (ajixmvsufl )
NCT01665144 (EXPAND, Pubmed)	Phase 3	Multiple Sclerosis, Secondary Progressive	779	Siponimod	bfzpfrfqmd(zszatfchmu) = dxdhyiqzwg ionaquwwow (gprtwppidy )	Positive	31 May 2022
				Placebo	bfzpfrfqmd(zszatfchmu) = aamznrewff ionaquwwow (gprtwppidy )
ACTRIMS2022	Not Applicable	Multiple Sclerosis antiCD20 therapies \| ocrelizumab \| fingolimod	-	OCR	(xsoxzweqnp) = bkrwlwkfaf stngpmjfbd (wbfjakylwm, 0.06 - 0.34) View more	Positive	16 May 2022
				Ofatumumab	(xsoxzweqnp) = pqnumhfyce stngpmjfbd (wbfjakylwm, 0.03 - 0.14) View more
P9-4.008 (AAN2022)	Not Applicable	Multiple Sclerosis	1,985	Diroximel Fumarate (DRF)	snixrzldyq(fyurfdyrtd) = oghbucwypd zdqvzvoanj (rgnwlfhfxw )	Positive	03 May 2022
				Dimethyl Fumarate (DMF)	snixrzldyq(fyurfdyrtd) = ebapqvgtmv zdqvzvoanj (rgnwlfhfxw )

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