IGHMBP2

WASHINGTON, Jan. 23, 2024 /PRNewswire/ -- Vanda Pharmaceuticals, Inc. (Vanda) (Nasdaq: VNDA) today announced that the U.S. Food and Drug Administration (FDA) has approved the Investigational New Drug (IND) application to evaluate VCA-894A for the treatment of a patient with Charcot-Marie-Tooth disease, axonal, type 2S (CMT2S), caused by cryptic splice site variants within the IGHMBP2 gene. CMT2S is a rare subtype of Charcot-Marie-Tooth disease (CMT), an inherited peripheral neuropathy for which there is no available treatment. CMT2S is characterized by slowly progressive distal muscle weakness and atrophy, affecting the upper and lower limbs in a child's first decade of life, leaving patients with decreased reflexes and sensory impairment1,2 The estimated overall prevalence of CMT is 1 in 2,500 individuals, with varying clinical features dependent on the various genetic variants of CMT.1,2 The prevalence of the CMT2S variant is estimated to be less than 1 in 1,000,000 worldwide.3 "This is an important milestone in the pursuit of personalized medicine, which has the potential to enable the development of treatments tailored to one's genetic variants, in this case specifically for a patient with CMT2S causing genetic mutations," said Mihael H. Polymeropoulos, M.D., Vanda's President, CEO and Chairman of the Board. VCA-894A is a novel antisense oligonucleotide (ASO) with a mechanism of action that specifically targets a cryptic splice site variant within immunoglobulin mu-binding protein 2 (IGHMBP2). Mutations within IGHMBP2 play a pivotal role in the manifestation of CMT2S, likely due to alpha-motor neuron loss, and consequently peripheral nervous system deterioration.4 ASOs have the capacity to modulate gene expression, allowing for the personalized treatment of rare diseases. Delivery of ASOs to the central nervous system has been previously successful in several ASO programs, with a broad applicability in addressing a number of neurodegenerative and neuromuscular disorders.5 References Cottenie, E., et al. (2014). Truncating and missense mutations in IGHMBP2 cause Charcot-Marie Tooth disease type 2. American journal of human genetics, 95(5), 590–601. Nam, S. H., & Choi, B-O. (2019). Clinical and genetic aspects of Charcot-Marie-Tooth disease subtypes." Precision and Future Medicine, 3(2), 43–68. (2023). Charcot-Marie-Tooth disease type 2S. Orpha.net. Rzepnikowska, W., & Kochański, A. (2021). Models for IGHMBP2-associated diseases: an overview and a roadmap for the future. Neuromuscular disorders: NMD, 31(12), 1266–1278. Crooke, S. T., Liang, X. H., Baker, B. F., & Crooke, R. M. (2021). Antisense technology: A review. The Journal of biological chemistry, 296, 100416. 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 Twitter @vandapharma. About VCA-894A VCA-894A is a 2'-O-methoxyethyl (MOE) phosphorothioate oligonucleotide sodium salt. VCA-894A specifically targets a cryptic splice site variant within IGHMBP2, which causes CMT2S. ASOs may have broad applicability in addressing a number of disorders, from nervous system treatments to systemic treatments. CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS Various statements in this press release, including, but not limited to statements regarding the estimated prevalence of CMT and CMT2S and the development of individualized treatments, are "forward-looking statements" under the securities laws. Forward-looking statements are based upon current expectations that involve risks, changes in circumstances, assumptions and uncertainties. Important factors that could cause actual results to differ materially from those reflected in Vanda's forward-looking statements include, among others, the accuracy of the reporting and diagnosis of CMT and CMT2S cases and the ability to successfully complete the clinical development of, and obtain regulatory approval for, VCA-894A in the treatment of CMT2S. 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 pr@vandapharma.com Company Codes: NASDAQ-NMS:VNDA

Q2 2023 total revenues were $46.1 million Total revenues in the first six months of 2023 were $108.6 million Vanda provides update on pipeline advancements and regulatory plans WASHINGTON, July 27, 2023 /PRNewswire/ -- Vanda Pharmaceuticals Inc. (Vanda) (Nasdaq: VNDA) today announced financial and operational results for the second quarter ended June 30, 2023. "During the second quarter we continued our efforts to protect our commercial interests in the HETLIOZ® franchise in the face of the at-risk generic launch. We recorded a higher number of HETLIOZ® prescription dispenses in the second quarter of 2023 as compared to the first quarter of 2023, a testament to our dedication to our patient services and the loyalty of our patients," said Mihael H. Polymeropoulos, M.D., Vanda's President, CEO and Chairman of the Board. "We also advanced towards our goal of marketing authorizations for Fanapt® in bipolar disorder, HETLIOZ® in insomnia and tradipitant in patients with gastroparesis." Financial Highlights Second Quarter of 2023 Total net product sales from HETLIOZ® and Fanapt® were $46.1 million in the second quarter of 2023, a 28% decrease compared to $64.4 million in the second quarter of 2022. HETLIOZ® net product sales were $22.0 million in the second quarter of 2023, a 47% decrease compared to $41.2 million in the second quarter of 2022. The decrease was the result of the at-risk launch of a generic version of HETLIOZ® in the U.S. Fanapt® net product sales were $24.1 million in the second quarter of 2023, a 4% increase compared to $23.2 million in the second quarter of 2022. Net income was $1.5 million in the second quarter of 2023 compared to net income of $2.6 million in the second quarter of 2022. Cash, cash equivalents and marketable securities (Cash) was $489.4 million as of June 30, 2023, representing a decrease to Cash of $12.1 million, or 2%, compared to March 31, 2023. First Six Months of 2023 Total net product sales from HETLIOZ® and Fanapt® were $108.6 million in the first six months of 2023, a 13% decrease compared to $124.6 million in the first six months of 2022. HETLIOZ® net product sales were $61.6 million in the first six months of 2023, a 21% decrease compared to $78.2 million in the first six months of 2022. The decrease was the result of the at-risk launch of a generic version of HETLIOZ® in the U.S. Fanapt® net product sales were $47.0 million in the first six months of 2023, a 1% increase compared to $46.4 million in the first six months of 2022. Net income was $4.8 million in the first six months of 2023 compared to a net loss of $3.9 million in the first six months of 2022. Cash, cash equivalents and marketable securities (Cash) was $489.4 million as of June 30, 2023, representing an increase to Cash of $48.5 million, or 11%, compared to June 30, 2022. Key Operational Highlights Fanapt® (iloperidone) Vanda previously announced positive results in the Phase III clinical study of Fanapt® in acute manic and mixed episodes associated with bipolar I disorder in adults. Vanda continues to pursue U.S. Food and Drug Administration (FDA) approval of a supplemental New Drug Application (sNDA) for Fanapt® in bipolar I disorder. HETLIOZ® (tasimelteon) Vanda is continuing to pursue FDA approvals for HETLIOZ® in the indications of insomnia and jet lag disorder. In May 2023, the U.S. Court of Appeals for the Federal Circuit (the Federal Circuit) affirmed the lower court ruling in favor of Teva Pharmaceuticals USA, Inc. (Teva), Apotex Inc. and Apotex Corp. (Apotex) in the HETLIOZ® Abbreviated New Drug Applications litigation. Vanda disagrees with the Federal Circuit's ruling, and in June 2023, Vanda requested a rehearing from the Federal Circuit. On July 18, 2023, the Federal Circuit requested a response from Teva and Apotex, which is due August 1, 2023. Tradipitant Vanda continues to pursue FDA approval of a New Drug Application (NDA) for tradipitant for patients with gastroparesis. Vanda announced positive results in the Phase III study of tradipitant in motion sickness. Vanda plans to continue the motion sickness clinical program and pursue FDA approval upon completion of additional efficacy and safety studies. Early-Stage Programs Vanda announced that the FDA had granted Orphan Drug Designation for VCA-894A for the treatment of Charcot-Marie-Tooth disease, axonal, type 2S (CMT2S), caused by cryptic splice site variants within IGHMBP2. GAAP Financial Results Net income was $1.5 million in the second quarter of 2023 compared to net income of $2.6 million in the second quarter of 2022. Diluted net income per share was $0.03 in the second quarter of 2023 compared to diluted net income per share of $0.05 in the second quarter of 2022. Net income was $4.8 million in the first six months of 2023 compared to a net loss of $3.9 million in the first six months of 2022. Diluted net income per share was $0.08 in the first six months of 2023 compared to diluted net loss per share of $0.07 in the first six months of 2022. 2023 Financial Guidance Given uncertainties surrounding the U.S. market for HETLIOZ® for the treatment of Non-24 as a result of the ongoing HETLIOZ® patent litigation and the at-risk launch of a generic version of HETLIOZ®, Vanda is unable to provide 2023 financial guidance at this time. Vanda will continue to evaluate its ability to provide financial guidance as the year progresses. HETLIOZ® net product sales will likely decline in future periods, potentially significantly, related to the at-risk launch of a generic version of HETLIOZ® in the U.S. Conference Call Vanda has scheduled a conference call for today, Thursday, July 27, 2023, at 4:30 PM ET. During the call, Vanda's management will discuss the second quarter 2023 financial results and other corporate activities. Investors can call 1-800-715-9871 (domestic) or 1-646-307-1963 (international) and use passcode number 4063687. A replay of the call will be available on Thursday, July 27, 2023, beginning at 8:30 PM ET and will be accessible until Thursday, August 3, 2023 at 8:30 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 4063687. 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. 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 Twitter @vandapharma. CAUTIONARY NOTE REGARDING FORWARD LOOKING STATEMENTS Various statements in this press release, including, but not limited to, statements regarding Vanda's plans for pursuit of FDA approval of Fanapt® in the treatment of bipolar I in adults, HETLIOZ® in the treatments of insomnia and jet lag disorder and tradipitant in the treatment of patients with gastroparesis and the treatment of motion sickness and Vanda's expectations regarding the impact of generic competition on the HETLIOZ® business 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 pursue and obtain FDA approval of the sNDAs for Fanapt® and HETLIOZ® and the NDA for tradipitant, the FDA's assessment of the sufficiency of the data packages to be included in Vanda's regulatory submissions for Fanapt®, HETLIOZ® and tradipitant, Vanda's ability to complete the clinical program for tradipitant in the treatment of motion sickness, the outcome of Vanda's request for a rehearing by the Federal Circuit and Vanda's ability to enforce its legal rights to exclusivity for HETLIOZ®. 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] Elizabeth Van Every Head of Corporate Affairs Vanda Pharmaceuticals Inc. 202-734-3400 [email protected] SOURCE Vanda Pharmaceuticals Inc.

WASHINGTON, June 1, 2023 /PRNewswire/ -- Vanda Pharmaceuticals Inc. (Vanda) (Nasdaq: VNDA) today announced the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation for VCA-894A for the treatment of Charcot-Marie-Tooth disease, axonal, type 2S (CMT2S), caused by cryptic splice site variants within IGHMBP2. CMT2S is a rare subtype of Charcot-Marie-Tooth disease (CMT), an inherited peripheral neuropathy for which there is no available treatment. The estimated prevalence of CMT is 1 in 2,500 individuals, with varying clinical features dependent on the various genetic variants of CMT.1,2 The prevalence of CMT2S is estimated to be less than 1 in 1,000,000 worldwide.3 Onset of CMT2S begins in early childhood.2 CMT2S is characterized by slowly progressive distal muscle weakness and atrophy, affecting the upper and lower limbs in a child's first decade of life, leaving patients with decreased reflexes and sensory impairment.1,2 Because CMT2S is a progressive disease, most patients become wheelchair bound. "This designation is an important milestone, which we believe may enable the development of individualized treatments tailored to one's genetic variants for patients with CMT2S," said Mihael H. Polymeropoulos, M.D., Vanda's President, CEO and Chairman of the Board. VCA-894A is a novel antisense oligonucleotide (ASO) with a mechanism of action that specifically targets a cryptic splice site variant within immunoglobulin mu-binding protein 2 (IGHMBP2). Mutations within IGHMBP2 play a pivotal role in the manifestation of CMT2S, likely due to alpha-motor neuron loss, and consequently peripheral nervous system deterioration.4 ASOs have the capacity to modulate gene expression, allowing for the personalized treatment of rare diseases. Delivery of ASOs to the central nervous system has been previously successful in several ASO programs, with a broad applicability in addressing a number of neurodegenerative and neuromuscular disorders.5 Orphan Drug Designation is granted by the FDA to investigational therapies addressing rare medical conditions and provides benefits to drug developers. References Cottenie, E., et al. (2014). Truncating and missense mutations in IGHMBP2 cause Charcot-Marie Tooth disease type 2. American journal of human genetics, 95(5), 590–601. Nam, S. H., & Choi, B-O. (2019). Clinical and genetic aspects of Charcot-Marie-Tooth disease subtypes." Precision and Future Medicine, 3(2), 43–68. (2023). Charcot-Marie-Tooth disease type 2S. Orpha.net. Rzepnikowska, W., & Kochański, A. (2021). Models for IGHMBP2-associated diseases: an overview and a roadmap for the future. Neuromuscular disorders: NMD, 31(12), 1266–1278. Crooke, S. T., Liang, X. H., Baker, B. F., & Crooke, R. M. (2021). Antisense technology: A review. The Journal of biological chemistry, 296, 100416. 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 Twitter @vandapharma. About VCA-894A VCA-894A is a 2'-O-methoxyethyl (MOE) phosphorothioate oligonucleotide sodium salt. VCA-894A specifically targets a cryptic splice site variant within IGHMBP2, which causes CMT2S. ASOs may have broad applicability in addressing a number of disorders, from nervous system treatments to systemic treatments. CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS Various statements in this press release, including, but not limited to statements regarding the estimated prevalence of CMT and CMT2S and the development of individualized treatments, are "forward-looking statements" under the securities laws. Forward-looking statements are based upon current expectations that involve risks, changes in circumstances, assumptions and uncertainties. Important factors that could cause actual results to differ materially from those reflected in Vanda's forward-looking statements include, among others, the accuracy of the reporting and diagnosis of CMT and CMT2S cases and the ability to successfully complete the clinical development of, and obtain regulatory approval for, VCA-894A in the treatment of CMT2S. 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] Elizabeth Van Every Head of Corporate Affairs Vanda Pharmaceuticals Inc. 202-734-3400 [email protected] SOURCE Vanda Pharmaceuticals Inc.