About Vanda Pharmaceuticals

Vanda Pharmaceuticals Inc. (Vanda) is a leading global biopharmaceutical company focuses on the development and commercialization of innovative therapies to address high unmet medical needs and improve the lives of patients. The company strives to advance novel approaches to bring important new medicines to market through responsible innovation. The company is committed to the use of technologies that support sound science, including genetics and genomics, in drug discovery, clinical trials and the commercial positioning of its products. The company’s commercial portfolio consists of three products, HETLIOZ for the treatment of Non-24-Hour Sleep-Wake Disorder (Non-24) and for the treatment of nighttime sleep disturbances in Smith-Magenis Syndrome (SMS), Fanapt for the treatment of schizophrenia and PONVORY, which it acquired the U.S. and Canadian rights to on December 7, 2023, for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease and active secondary progressive disease, in adults. HETLIOZ is the first product approved by the FDA for patients with Non-24 and for patients with SMS. In addition, the company has a number of drugs in development, including HETLIOZ (tasimelteon) for the treatment of jet lag disorder, insomnia, delayed sleep phase disorder (DSPD) and pediatric Non-24; Fanapt (iloperidone) for the treatment of bipolar I disorder and a long acting injectable (LAI) formulation for the treatment of schizophrenia; PONVORY (ponesimod) for the treatment of inflammatory/autoimmune disorders, including but not limited to ulcerative colitis, psoriasis, Crohn's disease, atopic dermatitis, eosinophilic esophagitis and alopecia areata; Tradipitant (VLY-686), a small molecule neurokinin-1 (NK-1) receptor antagonist, for the treatment of gastroparesis, motion sickness and atopic dermatitis; VHX-896, the active metabolite of iloperidone; Portfolio of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) activators and inhibitors, including VSJ-110 for the treatment of dry eye and ocular inflammation and VPO-227 for the treatment of secretory diarrhea disorders, including cholera; VTR-297, a small molecule histone deacetylase (HDAC) inhibitor for the treatment of onychomycosis, hematologic malignancies and with potential use as a treatment for several oncology indications; VQW-765, a small molecule nicotinic acetylcholine receptor partial agonist, for the treatment of social/performance anxiety and psychiatric disorders; and Antisense oligonucleotide (ASO) molecules, including VCA-894A for the treatment of Charcot-Marie-Tooth Disease, Type 2S (CMT2S), caused by cryptic slice site variants within IGHMBP2. Strategy The key elements of the company’s strategy are to maximize the commercial success of HETLIOZ, Fanapt and PONVORY; enter into strategic partnerships to supplement its capabilities and to extend its commercial reach; pursue the clinical development and regulatory approval of its products, including tradipitant; apply its pharmacogenetics and pharmacogenomics expertise to differentiate its products; expand its product portfolio through the identification and acquisition of additional products; and utilize novel and innovative approaches in pursuit of each of these strategies. Commercialized Products The company’s commercial product portfolio consists of: HETLIOZ for Non-24 (Capsules) In January 2014, HETLIOZ capsules were approved in the U.S. for the treatment of adults with Non-24. Non-24 is a serious, rare and chronic circadian rhythm sleep-wake disorder characterized by the inability to entrain (synchronize) the master body clock with the 24-hour day-night cycle. HETLIOZ is the first FDA approved treatment for Non-24. HETLIOZ is a melatonin agonist of the human MT1 and MT2 receptors, with greater specificity for MT2. These receptors are thought to be involved in the control of circadian rhythms. HETLIOZ was launched commercially in the U.S. in April 2014. In addition, in July 2015, the European Commission (EC) granted centralized marketing authorization with unified labeling for HETLIOZ for the treatment of Non-24 in totally blind adults and included post-marketing commitments related to a pediatric investigation plan. This authorization was renewed in July 2020 for an unlimited duration and is valid in the 27 countries that are members of the European Union (E.U.), as well as European Economic Area members Iceland, Liechtenstein and Norway. HETLIOZ was launched commercially in Germany in August 2016. In January 2010, the FDA granted orphan drug designation status for HETLIOZ in Non-24 in blind individuals. HETLIOZ for SMS (Capsules and Oral Suspension) In December 2020, HETLIOZ capsules and oral suspension (HETLIOZ LQ) were approved in the U.S. for the treatment of adults and children, respectively, with nighttime sleep disturbances in SMS. HETLIOZ capsules, for adults with SMS, were immediately available after approval and the HETLIOZ LQ liquid formulation, for children with SMS, became available in the first quarter of 2021. In April 2010, the FDA granted orphan drug designation status for HETLIOZ in the treatment of sleep disorder in SMS. SMS is estimated to affect 1/15,000-25,000 births in the U.S. SMS is not usually inherited but rather is caused by a de-novo deletion. Fanapt for Schizophrenia (Tablets) Fanapt is a product approved for the treatment of schizophrenia. In 2009, the FDA granted U.S. marketing approval of Fanapt for the acute treatment of schizophrenia in adults. At that time, the company had certain worldwide exclusive rights relating to Fanapt, which it obtained pursuant to a sublicense agreement entered into with Novartis Pharma AG (Novartis) in June 2004. In 2009, the company amended and restated its sublicense agreement with Novartis pursuant to which Novartis retained exclusive commercialization rights to all formulations of Fanapt in the U.S. and Canada. In January 2010, Novartis launched Fanapt in the U.S. On December 31, 2014, Novartis transferred all the U.S. and Canadian commercial rights to the Fanapt franchise to the company as part of a settlement agreement. Additionally, the company’s distribution partners launched Fanapt in Israel in 2014. In May 2016, the FDA approved a supplemental New Drug Application (sNDA) for Fanapt® for the maintenance treatment of schizophrenia in adults. PONVORY for Relapsing Multiple Sclerosis (Tablets) PONVORY is a product approved for the treatment of relapsing forms of MS (RMS), to include clinically isolated syndrome, relapsing-remitting disease and active secondary progressive disease, in adults. In December 2023, the company purchased the right to market and sell PONVORY in the U.S. and Canadian markets from Actelion Pharmaceuticals Ltd. (Janssen), a Johnson & Johnson Company. In March 2021, the FDA granted U.S. marketing approval of PONVORY for the treatment of RMS in adults. Health Canada approved PONVORY for the treatment of RMS in April 2021. 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. PONVORY was launched commercially in the U.S. in April 2021 and in Canada in November 2021 by one of the Johnson & Johnson Companies. There are a number of drugs approved and prescribed to treat patients with MS. See Competition below for a discussion of these commonly prescribed drugs. HETLIOZ for Jet Lag Disorder In March and May 2018, respectively, the company announced the results of ots JET8 and JET studies for the treatment of jet lag disorder. In the JET8 clinical study, HETLIOZ demonstrated significant and clinically meaningful benefits in nighttime and daytime symptoms of jet lag disorder, including improvement in sleep time and benefits in measurements of next day alertness. The FDA accepted the filing of the company’s sNDA for HETLIOZ for the treatment of jet lag disorder in December 2018. The FDA determined the action target action date under the Prescription Drug User Fee Act Amendments of 2017 to be August 16, 2019 and, on that date, the company received a complete response letter (CRL) from the FDA. The company filed a lawsuit against the FDA in September 2022 demanding that the FDA immediately publish in the Federal Register a notice of opportunity for a hearing on the jet lag disorder sNDA. HETLIOZ for Insomnia HETLIOZ is effective in improving sleep onset difficulty in people with primary insomnia with the effect observed as early as the first night of treatment. HETLIOZ for pediatric Non-24 The company plans to develop HETLIOZ for the treatment of pediatric Non-24. A pharmacokinetic study of the HETLIOZ pediatric liquid formulation was completed in 2018. HETLIOZ for DSPD A Phase III study of HETLIOZ in DSPD is ongoing. DSPD is a circadian rhythm disorder in which a person’s sleep is delayed beyond the socially acceptable or conventional bedtime. Fanapt for Bipolar I Disorder In December 2022, the company announced Fanapt was effective in the treatment of acute manic and mixed episodes associated with bipolar I disorder in adults in a randomized double-blind placebo controlled Phase III study. The primary endpoint measured in Week 4 of treatment was assessed by the Young Mania Rating Scale (YMRS), a rating scale of clinical severity in the core symptoms of mania. At the end of the 4-week study, Fanapt treated patients showed a larger improvement than placebo treated patients, and this difference was highly statistically significant. Statistically significant benefit in the Fanapt group over placebo was observed as early as the Week 2 assessment. In August 2023, the FDA accepted the company’s sNDA for Fanapt in bipolar I disorder in adults for filing and set a PDUFA target action date of April 2, 2024 for its decision. Fanapt for schizophrenia (LAI) In October 2018, the company enrolled its first patient in a pharmacokinetic study of the LAI formulation of Fanapt. This pharmacokinetic study is ongoing and will serve to inform the dosing for a later clinical study of Fanapt® LAI for the treatment of schizophrenia. PONVORY The mechanism of action of PONVORY makes it also a potential therapeutic candidate for the treatment of a diverse group of inflammatory/autoimmune disorders, including but not limited to ulcerative colitis, psoriasis, Crohn’s disease, atopic dermatitis, eosinophilic esophagitis and alopecia areata. In a randomized placebo controlled clinical study, PONVORY® has been shown to reduce the symptoms and signs of psoriasis. Tradipitant for Gastroparesis In December 2018, the company announced results from a Phase II randomized clinical study (2301) of tradipitant as a monotherapy in the treatment of gastroparesis. Several symptom severity scales were used to assess gastroparesis symptoms, including the Gastroparesis Symptom Index (GCSI), Patients Assessment of Upper Gastrointestinal Disorders-Symptoms (PAGI-SYM), and Patient Global Impression of Change (PGI-C) as well as a Clinician Global Impression of Severity (CGI-S). Tradipitant met the primary endpoint of the study of change in nausea score as measured by patient daily diaries and also met the related endpoint of improvement in the number of nausea free days. Tradipitant also showed significant improvement in most of the secondary endpoints studied, including several key scales reflecting overall gastroparesis symptoms, specifically GCSI, PAGI-SYM, CGI-S, and PGI-C. In February 2022, the company announced results from its Phase III clinical study, VP-VLY-686-3301, evaluating the efficacy and safety of tradipitant in treating the symptoms of gastroparesis. Tradipitant for motion sickness In July 2019, the company reported tradipitant was effective in treating motion sickness in a randomized double blind placebo controlled Phase II clinical study conducted in the Pacific Ocean. In May 2023, the company announced positive results from the first Phase III study of tradipitant in motion sickness, confirming the previously reported results demonstrating that tradipitant is effective in the prevention of vomiting associated with motion sickness. A second Phase III study of tradipitant in motion sickness is ongoing. Tradipitant for atopic dermatitis The company announced results in September 2017 from a randomized Phase II clinical study of tradipitant as a monotherapy in the treatment of patients with atopic dermatitis. Tradipitant was shown to improve the intensity of the worst itch patients experienced, as well as atopic dermatitis disease severity. In June 2018, the company initiated EPIONE, a Phase III study of tradipitant for pruritus in atopic dermatitis. In October 2019, the company began enrolling patients in EPIONE 2, a second Phase III clinical study of tradipitant in atopic dermatitis. VHX-896 In 2021, the company initiated a bioequivalence study of Fanapt and VHX-896, the active metabolite of iloperidone. Other Products VTR-297 In 2018, the company initiated a clinical study in patients with hematologic malignancies. Enrollment in the Phase I/II clinical study (1101) of VTR-297 in hematologic malignancies is ongoing. VTR-297 is a small molecule HDAC inhibitor with potential use as a treatment for several oncology indications. In January 2024, the FDA approved the company’s Investigational New Drug (IND) application to evaluate VTR-297 for the treatment of onychomycosis. Portfolio of CFTR activators and inhibitors A clinical program in VSJ-110 is ongoing. The company is evaluating VSJ-110 for the treatment of allergic conjunctivitis. VSJ-110 is a small molecule nanomolar potency CFTR activator. VSJ-110 has shown efficacy in a dry eye model and exhibited anti-inflammatory properties in both in vitro and in vivo assays. In addition, an early stage CFTR inhibitor program is planned for VPO-227 for the treatment of secretory diarrhea disorders, including cholera. VPO-227 has the potential to be an orally administered treatment for cholera. In October 2022, VPO-227 was granted orphan drug designation by the FDA for the treatment of cholera. VQW-765 The company is evaluating VQW-765 for the treatment of psychiatric disorders. In December 2022, the company announced results from its Phase II study, VP-VQW-765-2201 (Study 2201), of a single-dose treatment to alleviate acute performance anxiety in social situations. In the clinical study, 230 volunteers with prior history of performance anxiety were randomized to receive a single dose of VQW-765 or placebo and were challenged with the standardized Trier Social Stress Test (TSST). The TSST creates an acute stress by requiring participants to make an interview-style presentation in front of a panel who provides no feedback or encouragement. Participants who received VQW-765 showed numerically lower stress levels compared to those who received placebo. A significant relationship was also seen between exposure to VQW-765 (amount of drug measured in blood) and the clinical response. VQW-765 is a Phase II alpha-7 nicotinic acetylcholine receptor partial agonist that the company licensed from Novartis on December 31, 2014 pursuant to a settlement agreement. ASO Molecules In 2022, the company announced a research and development collaboration agreement with OliPass Corporation (OliPass) to jointly develop a set of ASO molecules based on OliPass’ proprietary modified peptide nucleic acids. The collaboration focuses on editing and modifying gene expression using ASOs in disease states where the expression of genes is either altered or the sequence of the expressed genes can be altered for therapeutic benefit. OliPass’ unique OliPass Peptide Nucleic Acids technology provides the delivery platform to enable these gene expression modifications. License Agreements The company’s rights to develop and commercialize its products are subject to the terms and conditions of licenses granted to it by other pharmaceutical companies. HETLIOZ: In February 2004, the company entered into a license agreement with BMS under which it received an exclusive worldwide license under certain patents and patent applications, and other licenses to intellectual property, to develop and commercialize HETLIOZ. The company is obligated to use its commercially reasonable efforts to develop and commercialize HETLIOZ. Fanapt: Pursuant to the terms of a settlement agreement with Novartis Pharma AG (Novartis), Novartis transferred all U.S. and Canadian rights in the Fanapt franchise to the company on December 31, 2014. The company paid directly to Sanofi S.A. (Sanofi) a fixed royalty of 3% of net sales through December 2019 related to manufacturing know-how. The company is also obligated to pay Sanofi a fixed royalty on Fanapt net sales equal to 6% on Sanofi know-how not related to manufacturing under certain conditions for a period of up to 10 years in markets where the new chemical entity (NCE) patent has expired or was not issued. The company is obligated to pay this 6% royalty on net sales in the U.S. through November 2026. Tradipitant: In 2012, the company entered into a license agreement with Eli Lilly and Company (Lilly) pursuant to which the Company acquired an exclusive worldwide license under certain patents and patent applications, and other licenses to intellectual property, to develop and commercialize an NK-1 receptor antagonist, tradipitant, for all human indications. Lilly is eligible to receive future payments based upon achievement of specified development, regulatory approval and commercialization milestones as well as tiered-royalties on net sales at percentage rates up to the low double digits. The company is obligated to use its commercially reasonable efforts to develop and commercialize tradipitant. Portfolio of CFTR activators and inhibitors: In March 2017, the company entered into a license agreement with the University of California San Francisco (UCSF), under which it acquired an exclusive worldwide license to develop and commercialize a portfolio of CFTR activators and inhibitors. VQW-765: In connection with a settlement agreement with Novartis relating to Fanapt, the company received an exclusive worldwide license under certain patents and patent applications, and other licenses to intellectual property, to develop and commercialize VQW-765, a Phase II alpha-7 nicotinic acetylcholine receptor partial agonist. Other Agreements In September 2022, the company entered into an agreement with OliPass Corporation (OliPass) to jointly develop a set of antisense oligonucleotide (ASO) molecules based on OliPass’ proprietary modified peptide nucleic acids. Patents and Proprietary Rights; Hatch-Waxman Protection PONVORY, tradipitant and VQW-765 are covered by NCE and other patents and patent applications related to their respective medicinal uses. In addition, NCE patent protection has been sought for VTR-297 and CFTR. Patent applications for these active ingredients remain pending. Although the NCE patents protecting Fanapt and HETLIOZ have expired, Fanapt remains protected by additional patents and HETLIOZ remains protected by additional patents, some of which the company has asserted against current generic competitors. HETLIOZ and HETLOZ LQ The company’s rights to the NCE patent covering HETLIOZ capsules and oral suspension (HETLIOZ LQ) and related intellectual property have been acquired through a license with BMS. HETLIOZ and its formulations, genetic markers and uses are the subject of numerous patent filings for which protection has been sought in selected countries worldwide. The NCE patent covering HETLIOZ expired in December 2022 in the U.S., which is inclusive of a five-year extension granted under the Hatch-Waxman Act in October 2018. Corresponding NCE patent protection has expired in most other markets. The U.S. Patent and Trademark Office has issued 22 method of treatment patents for HETLIOZ that will expire between 2033 and 2041 and four drug substance patents that will expire in 2035. Additionally, the U.S. Patent and Trademark Office has issued a drug formulation patent for HETLIOZ LQ that will expire in 2040. The company also has other pending patent applications covering methods of treatment and compositions of tasimelteon (HETLIOZ active ingredient) oral suspensions. The company filed several Hatch-Waxman lawsuits in the U.S. District Court for the District of Delaware (Delaware District Court) against Teva Pharmaceuticals USA, Inc. (Teva), Apotex Inc. (Apotex), MSN Pharmaceuticals, Inc. and MSN Laboratories Private Limited (MSN) (collectively, the HETLIOZ Defendants) asserting infringement of patents covering HETLIOZ 20 mg capsules. In January 2022, the company entered into a license agreement with MSN and Impax Laboratories LLC resolving the lawsuits against MSN. The consolidated lawsuits against the remaining HETLIOZ Defendants were tried in March 2022. In December 2022, the Delaware District Court ruled that Teva and Apotex did not infringe U.S. Patent No. RE46,604, and that the asserted claims of U.S. Patent Nos. RE46,604; 9,730,910; 10,149,829; and 10,376,487 were invalid. The company has appealed the decision to the U.S. Court of Appeals for the Federal Circuit (Federal Circuit) and in May 2023, a three-judge panel of the Federal Circuit affirmed the Delaware District Court’s ruling. In August 2023, the Federal Circuit denied its request for a rehearing. In January 2024, the company filed a petition for a writ of certiorari with the U.S. Supreme Court to review the Federal Circuit’s decision. The company has also filed Hatch-Waxman lawsuits in U.S. District Court for the District of New Jersey against each of Teva and Apotex and in the U.S. District Court for the Southern District of Florida against Apotex, in each case, asserting infringement of a method of administration patent that was not litigated in the Delaware District Court. The New Jersey cases have been transferred to the Delaware District Court, where they remain pending. The European Patent Office has granted the company’s patent application directed to the 20 mg/day dose. This patent will expire in 2027 and provides the basis for an SPC. Other pending patent applications in Europe, if granted, may offer additional protection for HETLIOZ. Outside the U.S. and Europe, data exclusivity will protect HETLIOZ from generic competition for varying numbers of years depending on the country. Additional patent applications directed to specific sleep disorders and to methods of treating patients with HETLIOZ, if issued, could provide exclusivity for such indications and methods of treatment. Fanapt The NCE patent for Fanapt, which expired in 2016 in the U.S. and in 2010 in other countries, was owned by Sanofi. Other patents and patent applications relating to Fanapt are owned by the company. Fanapt metabolites, formulations, genetic markers and uses are the subject of numerous patent filings in which protection has been sought in the U.S., Europe, and other markets. In November 2013, a U.S. patent (U.S. 8,586,610) directed to a method of treating patients with Fanapt based on genotype was issued to the company by the U.S. Patent and Trademark Office. PONVORY Janssen has obtained patent protection for PONVORY and its formulations in selected countries worldwide, including the U.S. and Canada. In December 2023, the company acquired all rights that Janssen had in U.S. and Canadian patents related to PONVORY, pending U.S. and Canada patent applications related to PONVORY, and any further U.S. and Canadian derivative patents and patent applications arising from the foregoing patents and pending patent applications. Regulatory exclusivity (NCE) protecting PONVORY in the U.S. will expire on March 18, 2026. The NCE patent covering the active ingredient in PONVORY (Reissue Patent No. 43,728) is set to expire on November 16, 2024, but an application for term extension pursuant to the Hatch-Waxman Act was submitted, which would extend this patent’s term to November 16, 2029 if granted. The U.S. Patent and Trademark Office has granted additional patents, including a further patent directed to a crystalline form of the active ingredient in PONVORY, which will expire in May 2032 in view of awarded patent term adjustment. The U.S. Patent and Trademark Office has also issued three method of treatment patents for PONVORY, which will expire between November 2024 and December 2035. Furthermore, on January 24, 2024, the U.S. Patent and Trademark Office issued a Notice of Allowance in the case of U.S. Pat. Appl. No. 17/962,968, which covers other methods of treatment using the active ingredient in PONVORY®. Once issued, this patent would be expected to expire on October 10, 2042. Also, a number of patent applications covering further methods of treatment remain pending at the U.S. Patent and Trademark Office. In Canada, the Patented Medicines (Notice of Compliance) Regulations (PM(NOC) Regulations) create a regime analogous to the Hatch-Waxman Act and link the regulatory approval process for generic and biosimilar drugs to the adjudication of innovator patent rights. To be eligible for protection under the PM(NOC) Regulations, patents must first be listed on the Patent Register in connection with an innovator’s drug submission to Health Canada. A generic or biosimilar manufacturer must then provide notice to the innovator of its plans to market a drug that it compared to the innovator’s patented drug in the Health Canada approval process. Within 45 days of receiving such a notice of allegation, an innovator drug company may commence patent infringement proceedings against the generic or biosimilar manufacturer. The commencement of an action by the innovator under the PM(NOC) Regulations may stay Health Canada’s regulatory approval of the generic or biosimilar drug for a period of 24 months. It is also possible that protection through a patent (i.e., a patent claiming a medicinal ingredient, or the combination of all medicinal ingredients, or uses thereof) in Canada can be extended for up to two years by the issuance of a Certificate of Supplementary Protection (CSP). Health Canada’s Patent Register lists Canadian Patent Nos. 2545582, 2740313, and 2968180 for PONVORY, which are respectively directed to the active ingredient in PONVORY, the crystalline form of that active ingredient, and methods of treatment. These listed patents will respectively expire November 16, 2024; October 19, 2029; and April 29, 2036 in view of the CSP. Tradipitant Lilly owns the NCE patent as well as patent applications directed to polymorphic forms of, and methods of making tradipitant. This patent protection was sought in the U.S. and in other countries worldwide. These patents and patent applications have been licensed to the company. The NCE patent covering tradipitant expired in April 2023, except in the U.S., where it expires normally in June 2024, subject to any extension that may be received under the Hatch-Waxman Act. The company has filed additional patent applications based on discoveries made during recent studies with tradipitant. VTR-297 VTR-297 is a small molecule HDAC inhibitor with potential use as a treatment for several oncology indications. The company has pending patent applications covering the use of VTR-297 and plans on filing additional applications based on discoveries made throughout the development plan of this molecule. Portfolio of CFTR activators and inhibitors VQW-765 Novartis owns the NCE patent, as well as patent applications directed to methods of using VQW-765, VQW-765 formulations, and combinations of VQW-765 with other active pharmaceutical ingredients. In connection with the settlement agreement with Novartis relating to Fanapt, the company received an exclusive worldwide license under certain patents and patent applications, and other licenses to intellectual property, to develop and commercialize VQW-765, a Phase II alpha-7 nicotinic acetylcholine receptor partial agonist. The NCE patent expired normally in 2023 in the U.S., Europe, and other markets. Other Patents The company has obtained or filed numerous patents and patent applications, most of which have been filed in key markets including the U.S., relating to its products and product candidates. In addition, the company has filed numerous other patent applications relating to drugs not presently in clinical studies. Marketing and Sales HETLIOZ capsules were approved in the U.S. for the treatment of Non-24 in January 2014 and HETLIOZ capsules and oral suspension were approved for the treatment of nighttime sleep disturbances in SMS in December 2020. The company commercially launched HETLIOZ capsules in the U.S. in April 2014 and the oral suspension in March 2021. Additionally, HETLIOZ capsules were approved in the E.U. for the treatment of Non-24 in totally blind adults in July 2015 and, in August 2016, the company commercially launched HETLIOZ in Germany. Fanapt oral tablets were approved in the U.S. for the treatment of schizophrenia in 2009 and commercially launched in the U.S. in January 2010. The company continues to explore the regulatory path and commercial opportunity for Fanapt oral formulation in other regions. PONVORY tablets were approved in the U.S. for the treatment of RMS in adults in March 2021 and commercially launched in the U.S. by Janssen in April 2021. PONVORY tablets were approved in Canada for the treatment of RMS in adults in 2021 and commercially launched in Canada by Janssen in 2021. The company acquired the U.S. and Canadian rights to PONVORY in December 2023 from Janssen. Janssen will continue PONVORY operations during a transition period, following which, regulatory and supply responsibilities will be transitioned to the company. Major Customers The company’s revenues are generated from product sales and are concentrated with two specialty pharmacies and three wholesalers. There were five major customers that each accounted for more than 10% of total revenues for 2023 and, as a group, represented 80% of total revenues for the year ended December 31, 2023. Manufacturing The company has agreements in place with Patheon Pharmaceuticals Inc. and Patheon Inc. (collectively, Patheon), subsidiaries of Thermo Fisher Scientific, for the manufacture of HETLIOZ capsules and Fanapt® oral tablets. In January 2014, the company entered into a manufacturing agreement with Patheon for the manufacture of commercial supplies of HETLIOZ 20 mg capsules at Patheon’s Cincinnati, Ohio manufacturing site. Under the HETLIOZ manufacturing agreement, it is responsible for supplying the active pharmaceutical ingredient (tasimelteon) for HETLIOZ to Patheon and have agreed to order from Patheon at least 80% of the total expected yearly production of new units of HETLIOZ capsules. Patheon is responsible for manufacturing the HETLIOZ 20 mg capsules, conducting quality control and stability testing, and packaging the HETLIOZ capsules. The HETLIOZ manufacturing agreement had an initial term of five years and automatically renews after the initial term for successive terms of one year each, unless either party gives notice of its intention to terminate the agreement at least 12 months prior to the end of the then current term. As part of a settlement agreement in 2014, the company assumed Novartis’ manufacturing agreement with Patheon for the manufacture of commercial supplies of Fanapt. In May 2016, the company entered into a new manufacturing agreement with Patheon for the manufacture of commercial supplies of Fanapt 1, 2, 4, 6, 8, 10 and 12 mg tablets at Patheon’s Mississauga, Ontario, Canada manufacturing site. Under the Fanapt manufacturing agreement, the company is responsible for sourcing the supply of the active pharmaceutical ingredient (iloperidone), and has agreed to order from Patheon at least 70% of the total expected yearly production of new units of Fanapt tablets for the U.S. and other specified countries each year for the term of the agreement. Patheon is responsible for manufacturing the Fanapt 1, 2, 4, 6, 8, 10 and 12 mg tablets, conducting quality control and stability testing, and packaging the Fanapt tablets. The Fanapt manufacturing agreement had an initial term of five years and automatically renews after the initial term for successive terms of one year each, unless either party gives notice of its intention to terminate the agreement at least 12 months prior to the end of the then current term. In December 2020, the company entered into a non-exclusive manufacturing agreement for the manufacture of commercial supplies of both 48 mL and 158 mL HETLIOZ LQ bottles. The HETLIOZ LQ manufacturing agreement has an initial term of five years and automatically renews after the initial term for successive terms of one year each, unless either party gives notice of its intention to terminate the agreement at least 12 months prior to the end of the then current term. PONVORY is manufactured by third parties and supplied to Jannsen, which is distributing PONVORY pursuant to the terms of a transition agreement. During the transition period, Vanda and Janssen will transition supply responsibility for PONVORY to the company. Government Regulation The company’s approved products are, and any additional product manufactured or distributed by it following FDA approval will be, subject to continuing regulation by the FDA, including among other things, recordkeeping requirements, reporting of adverse experiences with the drug, providing the FDA with updated safety and efficacy information, drug sampling and distribution requirements, complying with certain electronic records and signature requirements, and complying with FDA promotion and advertising requirements. Research and Development The company’s research and development expenses were $76.8 million for the year ended December 31, 2023. History Vanda Pharmaceuticals Inc. was founded in 2002. The company was incorporated in Delaware in 2002.