The aim of this study is to investigate the safety and tolerability of trichostatin A in individuals with relapsed or refractory hematologic malignancies.

Start Date27 Sep 2018

Sponsor / Collaborator

Vanda Pharmaceuticals, Inc.

100 Clinical Results associated with Trichostatin A

100 Translational Medicine associated with Trichostatin A

100 Patents (Medical) associated with Trichostatin A

5,652

Literatures (Medical) associated with Trichostatin A

01 Mar 2024·Clinical orthopaedics and related research

Variations in 1-year Trajectories of Levels of Pain and Capability After Shoulder Arthroplasty Are Associated With Baseline Mental Health

Article

Author: van den Bekerom, Michel ; Broekman, Melle Martijn ; Brinkman, Niels ; Swanson, Daniel ; Ring, David ; Jawa, Andrew

Abstract:

Background:

There is variability in the trajectories of pain intensity and magnitude of incapability after shoulder arthroplasty. A better understanding of the degree to which variation in recovery trajectories relates to aspects of mental health can inform the development of comprehensive biopsychosocial care strategies.

Questions/purposes:

(1) Do pain intensities at baseline and the trajectories during recovery differ between groups when stratified by mental health composite summary score, arthroplasty type, and revision surgery? (2) Do magnitudes of capability at baseline and the trajectories during recovery differ between these groups?

Methods:

We used a registry of 755 patients who underwent shoulder arthroplasty by a single surgeon at a specialized urban orthopaedic hospital that recorded the mental component summary (MCS) score of the Veterans RAND 12, a measure of shoulder-specific comfort and capability (American Shoulder and Elbow Surgeons [ASES] score, which ranges from 0 to 100 points, with a score of 0 indicating worse capability and pain and 100 indicating better capability and pain and a minimum clinically important difference of 6.4), and the VAS for pain intensity (range 0 [representing no pain] to 10 [representing the worst pain possible], with a minimum clinically important difference of 1.4) preoperatively, 2 weeks postoperatively, and 6 weeks, 3 months, 6 months, and 1 year after surgery. Forty-nine percent (368 of 755) of the patients were men, with a mean age of 68 ± 8 years, and 77% (585) were treated with reverse total shoulder arthroplasty (rTSA). Unconditional linear and quadratic growth models were generated to identify the general shape of recovery for both outcomes (linear versus quadratic). We then constructed conditional growth models and curves for pain intensity and the magnitude of capability showing mean baseline scores and the rates of recovery that determine the trajectory, accounting for mental health (MCS) quartiles, primary or revision arthroplasty, and TSA or reverse TSA in separate models. Because pain intensity and capability showed quadratic trends, we created trajectories using the square of time.

Results:

Patients in the worst two MCS quartiles had greater pain intensity at baseline than patients in the best quartile (difference in baseline for bottom quartile: 0.93 [95% CI 0.72 to 1.1]; p < 0.01; difference in baseline for next-worst quartile: 0.36 [95% CI 0.16 to 0.57]; p < 0.01). The rates of change in recovery from pain intensity were not different among groups (p > 0.10). Patients with revision surgery had greater baseline pain (difference: 1.1 [95% CI 0.7 to 1.5]; p < 0.01) but no difference in rates of recovery (difference: 0.031 [95% CI 0.035 to 0.097]; p = 0.36). There were no differences in baseline pain intensity and rates of recovery between patients with reverse TSA and those with TSA (baseline pain difference: -0.20 [95% CI -0.38 to -0.03]; p = 0.18; difference in rate of recovery: -0.005 [95% CI -0.035 to 0.025]; p = 0.74). Patients in the worst two MCS quartiles had worse baseline capability than patients in the best quartile (difference in baseline for bottom quartile: -8.9 [95% CI -10 to -7.4]; p < 0.001; difference in baseline for the next-worst quartile: -4.9 [95% CI -6.4 to -3.4]; p < 0.01), with no differences in rates of recovery (p > 0.10). Patients with revision surgery had lower baseline capability (difference in baseline: -13 [95% CI -15 to -9.7]; p < 0.01), with a slower rate of recovery (difference in rate of recovery: -0.56 [95% CI -1.0 to -0.079]; p = 0.021). There were no differences in baseline capability or rates of recovery between TSA and reverse TSA.

Conclusion:

The observation that preoperative and 1-year comfort and capability are associated with mental health factors and with similar recovery trajectories reminds us that assessment and treatment of mental health is best considered an integral aspect of musculoskeletal care. Future studies can address how prioritization of mental health in musculoskeletal care strategies might reduce variation in the 1-year outcomes of discretionary surgeries such as shoulder arthroplasty.

Level of Evidence:

Level III, therapeutic study.

01 Feb 2024·Biochimica et biophysica acta. General subjects

Manipulating epigenetic diversity in crop plants: Techniques, challenges and opportunities

Review

Author: Kumar, Jitendra ; Saini, Dinesh Kumar ; Chauhan, Sunena ; Khandare, Kiran ; Gahlaut, Vijay ; Ahmed, Shoeb ; Singh, Vikas Kumar ; Sharma, Pradeep Kumar ; Kumar, Ashutosh

Epigenetic modifications act as conductors of inheritable alterations in gene expression, all while keeping the DNA sequence intact, thereby playing a pivotal role in shaping plant growth and development. This review article presents an overview of techniques employed to investigate and manipulate epigenetic diversity in crop plants, focusing on both naturally occurring and artificially induced epialleles. The significance of epigenetic modifications in facilitating adaptive responses is explored through the examination of how various biotic and abiotic stresses impact them. Further, environmental chemicals are explored for their role in inducing epigenetic changes, particularly focusing on inhibitors of DNA methylation like 5-AzaC and zebularine, as well as inhibitors of histone deacetylation including trichostatin A and sodium butyrate. The review delves into various approaches for generating epialleles, including tissue culture techniques, mutagenesis, and grafting, elucidating their potential to induce heritable epigenetic modifications in plants. In addition, the ground breaking CRISPR/Cas is emphasized for its accuracy in targeting specific epigenetic changes. This presents a potent tools for deciphering the intricacies of epigenetic mechanisms. Furthermore, the intricate relationship between epigenetic modifications and non-coding RNA expression, including siRNAs and miRNAs, is investigated. The emerging role of exo-RNAi in epigenetic regulation is also introduced, unveiling its promising potential for future applications. The article concludes by addressing the opportunities and challenges presented by these techniques, emphasizing their implications for crop improvement. Conclusively, this extensive review provides valuable insights into the intricate realm of epigenetic changes, illuminating their significance in phenotypic plasticity and their potential in advancing crop improvement.

01 Feb 2024·Journal of shoulder and elbow surgery

Functional and radiographic results of anatomic total shoulder arthroplasty in the setting of subscapularis dysfunction: 5-year outcomes analysis

Article

Author: Levy, Jonathan C ; Lewis, Steven ; Rodriguez, Hugo C ; Cannon, Dylan ; Schodlbauer, Daniel ; Vegas, Austin ; Mekkawy, Kevin L ; Glener, Julie

BACKGROUND:

Subscapularis management is a critical component to the success of anatomic total shoulder arthroplasty (TSA). Failure to heal the subscapularis can result in pain, weakness, loss of function, and revision. However, not all patients have poor outcomes. The purpose of this study is to compare patients with normal and dysfunctional subscapularis function following TSA in regard to (1) patient-reported outcome measures (PROMs); (2) range of motion (ROM) and strength; (3) achievement of minimal clinically important differences (MCIDs); and (4) specific functional internal rotation tasks.

METHODS:

A retrospective review of patients treated with TSA for osteoarthritis with a minimum 2-year follow-up was performed to identify patients with subscapularis dysfunction. Subscapularis dysfunction was diagnosed when any degree of weakness in internal rotation was detected on physical examination (positive belly press sign). These patients were case controlled matched on a 1:3 ratio to patients with normal subscapularis function based on age and sex. PROMs, measured active motion, revision rates, patient satisfaction, and postoperative radiographic findings were compared. Population-specific institutional anchor-based MCID values were used to compare the improvement in PROM.

RESULTS:

Of the 668 patients included, 34 patients (5.1%) demonstrated evidence of subscapularis dysfunction. Mean follow-up for the normal subscapularis function cohort was 63.4 ± 29.7 and 58.7 ± 26.8 for the dysfunctional subscapularis cohort. Patients with subscapularis dysfunction demonstrated significantly worse postoperative Simple Shoulder Test, Single Assessment Numerical Evaluation, visual analog scale (VAS) function, VAS pain, and American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) scores with higher rates of unsatisfactory results when compared to patients with normal subscapularis function. Abduction, elevation, internal rotation ROM, along with supraspinatus and external rotation strength were also significantly worse in the dysfunctional group. Similarly, these patients were more likely to have decreased ability to perform functional internal rotation tasks, with only 47% of the patients being able to reach the small of their back compared to 85% with normal subscapularis function. Radiographically, the dysfunctional cohort demonstrated higher rates of anterior subluxation (56% vs. 7%; P < .001) and glenoid loosening (24% vs. 5%; P = .004). Similarly, revision rates were significantly higher for patients with subscapularis dysfunction (8 patients, 23.5%). Nonetheless, the dysfunctional subscapularis cohort demonstrated improvements in VAS pain (4.0 ± 3.7) and ASES (46.4 ± 35.9) scores that exceeded MCID thresholds.

CONCLUSION:

Patients who develop subscapularis dysfunction after TSA have significantly worse PROMs, ROM, functional tasks of internal rotation, and radiographic outcomes, as well as increased rates of revision. Although patients show worse outcomes and high revision rates compared with their normal-functioning counterparts, these patients maintained improvement above MCID thresholds for pain and function at a mean 5-year follow-up.

News (Medical) associated with Trichostatin A

08 May 2024

·www.prnewswire.com

Vanda Pharmaceuticals Reports First Quarter 2024 Financial Results

Revenues for Q1 2024 were $47.5 million, an increase of 5% compared to Q4 2023 Cash increase of $5.9 million in Q1 2024 to $394.1 million Fanapt® approved for the acute treatment of bipolar I disorder; commercial launch expected in Q3 2024 Milsaperidone NDA for schizophrenia and bipolar disorder expected to be submitted in early-2025 PONVORY® commercial launch expected in Q3 2024 Tradipitant NDA review for gastroparesis ongoing, PDUFA date of September 18, 2024 Tradipitant second Phase III motion sickness study results expected in Q2 2024; NDA expected to be submitted in Q4 2024 WASHINGTON, May 8, 2024 /PRNewswire/ -- Vanda Pharmaceuticals Inc. (Vanda) (Nasdaq: VNDA) today announced financial and operational results for the first quarter ended March 31, 2024. "We are very proud of our accomplishments in the first quarter of 2024, which were achieved with a small but efficient organization that is enthusiastic to continue developing and commercializing treatments for people who need them," said Mihael H. Polymeropoulos, M.D., Vanda's President, CEO and Chairman of the Board. "We expect several significant milestones in the coming months, including the launch of Fanapt in acute bipolar I disorder, the launch of Ponvory in multiple sclerosis, the potential approval of tradipitant in gastroparesis, the phase III results of tradipitant in motion sickness, the upcoming NDA filings of milsaperidone in psychiatric disorders and of tradipitant in motion sickness and the initiation of clinical programs in depression, psoriasis, ulcerative colitis and pediatric insomnia. We are confident that our robust revenue, strong cash position and efficient operations position us well for significant growth and value creation in the years to come." Financial Highlights Total net product sales from Fanapt®, HETLIOZ® and PONVORY® were $47.5 million in the first quarter of 2024, a 24% decrease compared to $62.5 million in the first quarter of 2023, and a 5% increase compared to $45.3 million in the fourth quarter of 2023. Fanapt® net product sales were $20.6 million in the first quarter of 2024, a 10% decrease compared to $22.9 million in the first quarter of 2023, and a 9% decrease compared to $22.6 million in the fourth quarter of 2023. HETLIOZ® net product sales were $20.1 million in the first quarter of 2024, a 49% decrease compared to $39.6 million in the first quarter of 2023, and a 5% decrease compared to $21.1 million in the fourth quarter of 2023. The decrease relative to the first quarter of 2023 was the result of continued generic competition in the U.S. PONVORY® net product sales were $6.8 million in the first quarter of 2024. The acquisition of PONVORY® from Actelion Pharmaceuticals Ltd. (Janssen), a Johnson & Johnson Company, was completed on December 7, 2023. Net loss was $4.1 million in the first quarter of 2024, compared to net income of $3.3 million in the first quarter of 2023, and net loss of $2.4 million in the fourth quarter of 2023. Cash, cash equivalents and marketable securities (Cash) was $394.1 million as of March 31, 2024, representing an increase to Cash of $5.9 million compared to December 31, 2023. Key Operational Highlights Psychiatry Portfolio Fanapt® (iloperidone): Vanda announced in April 2024 that the U.S. Food and Drug Administration (FDA) approved Fanapt® as a first line treatment of acute bipolar I disorder in adults. This approval of Fanapt® for acute bipolar I disorder significantly expands the addressable patient population. Patent exclusivity is expected to last at least through late 2027. Vanda is initiating a host of commercial activities, including the expansion of its existing sales force, a prescriber awareness program and a comprehensive marketing program. Milsaperidone: Vanda expects to submit a New Drug Application (NDA) for milsaperidone (also known as VHX-896 and P-88), the active metabolite of Fanapt®, in schizophrenia and acute bipolar I disorder to the FDA in early-2025. If approved, there are pending patent applications that, if issued, could extend exclusivity into the 2040s. Fanapt® LAI: Vanda expects to initiate a Phase III program for the long acting injectable (LAI) formulation of Fanapt® by the end of 2024. Fanapt® LAI could reach the U.S. market after 2026 and there are pending patent applications that, if issued, could extend exclusivity into the 2040s. Vanda is currently planning clinical programs to test the efficacy of Fanapt® and milsaperidone in the treatment of depressive symptoms which, if successful, will significantly expand the addressable patient population. HETLIOZ® (tasimelteon) Vanda is currently planning to initiate a HETLIOZ LQ® program in pediatric insomnia. Although exact estimates of prevalence of insomnia in children are difficult to quantify, it is estimated that 20-40% of children experience significant sleep problems.1,2 There are currently no approved treatments for pediatric insomnia. If ultimately approved for marketing, the addressable patient population for HETLIOZ LQ® would be significantly expanded and market exclusivity would be expected to last into the 2040s. Vanda announced in March 2024 that it received a complete response letter (CRL) from the FDA related to the supplemental New Drug Application (sNDA) for HETLIOZ® in the treatment of insomnia. Vanda is reviewing the CRL and evaluating its next steps. In addition to insomnia, Vanda continues to pursue FDA approval of HETLIOZ® in the treatment of jet lag disorder where the final agency rejection of our application is being challenged in the U.S. Court of Appeals for the D.C. Circuit. Vanda announced in April 2024 that the U.S. Supreme Court denied its petition for a writ of certiorari to review the decision of the U.S. Court of Appeals for the Federal Circuit in Vanda's HETLIOZ® Abbreviated New Drug Application litigation against Teva Pharmaceuticals USA, Inc. (Teva), Apotex Inc. and Apotex Corp (together, Apotex). The lower court decision held that certain claims of Vanda's U.S. Patent Nos. RE46,604; 9,730,910; 10,149,829; and 10,376,487 were invalid. Vanda's suit asserting U.S. Patent No. 11,285,129 will be infringed by Teva's and Apotex's generic versions of HETLIOZ® is currently pending in the U.S. District Court for the District of Delaware. PONVORY® (ponesimod) Vanda expects to complete the transition of PONVORY® from Janssen and commercially launch the product for multiple sclerosis in the third quarter of 2024. Vanda is initiating a host of commercial activities including the creation of a specialty sales force, a prescriber awareness program and a comprehensive marketing program. Currently approved as a once-a-day oral treatment for people with multiple sclerosis, PONVORY® has a differentiated profile from other drugs in the class with high specificity and rapid reversibility, making for a versatile use to address the needs of people with multiple sclerosis and exclusivity is expected to last into the 2040s. Positive results from a Phase II clinical study for PONVORY® in the treatment of psoriasis were previously published in Lancet where PONVORY® demonstrated significant effects in both induction and maintenance of response.3 Vanda expects to file an Investigational New Drug (IND) application with the FDA for PONVORY® in the treatment of psoriasis. Vanda expects to initiate a Phase III study for PONVORY® in the treatment of psoriasis by the end of 2024. If ultimately approved for marketing, PONVORY® would be the first oral sphingosine-1-phosphate (S1P) analog approved for the treatment of psoriasis and would significantly expand the addressable patient population of PONVORY®, with over 8 million people diagnosed with psoriasis in the U.S.4 Vanda expects to file an IND application with the FDA for PONVORY® in the treatment of ulcerative colitis. Vanda expects to initiate a Phase III study for PONVORY® in the treatment of ulcerative colitis by the end of 2024. If ultimately approved for marketing, PONVORY® would follow other oral sphingosine-1-phosphate (S1P) analogs approved for the treatment of ulcerative colitis and would significantly expand the addressable patient population of PONVORY®, with an estimated prevalence in the U.S. of approximately 2 million individuals.5 Tradipitant The NDA for tradipitant for the treatment of symptoms of gastroparesis is under review by the FDA with a PDUFA target action date of September 18, 2024. Gastroparesis is a significant unmet medical need with the last treatment option approved over 40 years ago and an estimated prevalence in the U.S. of over 6 million individuals.6 The second Phase III clinical study of tradipitant in the treatment of motion sickness is fully enrolled and results are expected in the second quarter of 2024. The efficacy of tradipitant in the treatment of motion sickness has previously been demonstrated in two clinical studies in which tradipitant was effective in preventing vomiting associated with motion. Vanda expects to submit an NDA for the treatment of motion sickness to the FDA in the fourth quarter of 2024. An eventual NDA approval of tradipitant in the treatment of motion sickness would significantly expand the addressable patient population, with approximately 30% of the U.S. population reported to suffer from motion sickness under ordinary travel conditions that include sea, air and land.7 Early-Stage Programs The Phase II study of VSJ-110 for the treatment of dry eye is ongoing and more than 50% enrolled. The Phase I clinical study for VCA-894A in the treatment of a patient with Charcot-Marie-Tooth disease, axonal, type 2S (CMT2S), an inherited peripheral neuropathy for which there is no available treatment, expects to enroll the patient in mid-2024. The Phase I clinical study of VTR-297 for the treatment of onychomycosis, a fungal infection of the nail, was initiated in April 2024. VQW-765, an alpha-7 nicotinic acetylcholine receptor partial agonist, is currently in clinical development for treatment of acute performance anxiety in social situations. GAAP Financial Results Net loss was $4.1 million in the first quarter of 2024 compared to net income of $3.3 million in the first quarter of 2023. Diluted net loss per share was $0.07 in the first quarter of 2024 compared to diluted net income per share of $0.06 in the first quarter of 2023. 2024 Financial Guidance Given continuing uncertainties surrounding the U.S. market for HETLIOZ® for the treatment of Non-24 as a result of continued generic competition in the U.S. and the upcoming commercial launches for Fanapt® in acute bipolar I disorder and PONVORY® in multiple sclerosis, Vanda is unable to provide 2024 financial guidance at this time. Conference Call Vanda has scheduled a conference call for today, Wednesday, May 8, 2024, at 4:30 PM ET. During the call, Vanda's management will discuss the first quarter 2024 financial results and other corporate activities. Investors can call 1-800-715-9871 (domestic) or 1-646-307-1963 (international) and use passcode number 2594340. A replay of the call will be available on Wednesday, May 8, 2024, beginning at 8:30 PM ET and will be accessible until Wednesday, May 15, 2024 at 11:59 PM ET. The replay call-in number is 1-800-770-2030 for domestic callers and 1-609-800-9909 for international callers. The passcode number is 2594340. The conference call will be broadcast simultaneously on Vanda's website, . Investors should click on the Investors tab and are advised to go to the website at least 15 minutes early to register, download, and install any necessary software or presentations. The call will also be archived on Vanda's website for a period of 30 days. References Calhoun SL, Fernandez-Mendoza J, Vgontzas AN, Liao D, Bixler EO. Prevalence of insomnia symptoms in a general population sample of young children and preadolescents: gender effects. Sleep Med. 2014 Jan;15(1):91-5. doi: 10.1016/j.sleep.2013.08.787. Epub 2013 Oct 16. PMID: 24333223; PMCID: PMC3912735. Fricke-Oerkermann L, Plück J, Schredl M, Heinz K, Mitschke A, Wiater A, Lehmkuhl G. Prevalence and course of sleep problems in childhood. Sleep. 2007 Oct;30(10):1371-7. doi: 10.1093/sleep/30.10.1371. PMID: 17969471; PMCID: PMC2266270. Vaclavkova A, Chimenti S, Arenberger P, Holló P, Sator PG, Burcklen M, Stefani M, D'Ambrosio D. Oral ponesimod in patients with chronic plaque psoriasis: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet. 2014 Dec 6;384(9959):2036-45. doi: 10.1016/S0140-6736(14)60803-5. Epub 2014 Aug 10. PMID: 25127208. Datamonitor Healthcare – Psoriasis Patient-Based Market Forecast published March 2023. Datamonitor Healthcare – Ulcerative Colitis Patient-Based Market Forecast published March 2023. Rey et al J Neurogastroenterol Motil, Jan 2012. Turner M, Griffin MJ. Motion sickness in public road transport: passenger behavior and susceptibility. Ergonomics. 1999: 42: 444-461. 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 advancement of Vanda's clinical development pipeline and strengthening of its commercial presence, Vanda's plans for pursuit of FDA approval of tradipitant in the treatment of symptoms of gastroparesis and the treatment of motion sickness, HETLIOZ® in the treatments of insomnia and jet lag disorder, Vanda's expectations regarding the timing of the FDA's decisions with respect to the sNDAs for HETLIOZ® and the NDA for tradipitant, Vanda's plans for a LAI formulation of Fanapt®, the timing of a submission of an NDA for milsaperidone, the potential for PONVORY® to treat psoriasis and ulcerative colitis, the planned patient enrollment for a clinical study for VCA-894A, the planned launch of PONVORY® in the US and the ongoing launch of Fanapt® in acute bipolar I disorder, the planned clinical programs to test Fanapt® and milsaperidone in depressive symptoms and the planned Hetlioz LQ® program in pediatric insomnia 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 complete the clinical development of the products in its pipeline and obtain regulatory approval and market acceptance of these products, Vanda's ability to obtain FDA approval of the sNDAs for HETLIOZ® and the NDA for tradipitant, the FDA's ability to meet the PDUFA target action date for the NDA for tradipitant, the FDA's assessment of the sufficiency of the data packages included in Vanda's regulatory submissions for HETLIOZ® and tradipitant, Vanda's ability to obtain approval for milsaperidone in the treatment of schizophrenia and acute bipolar I disorder, the results of any clinical trials conducted for PONVORY® in the treatment of other inflammatory/autoimmune disorders, Vanda's ability to obtain regulatory approval of HETLIOZ® and PONVORY® for any additional indications, Vanda's ability to complete the clinical program for tradipitant in the treatment of motion sickness, the planned clinical programs to test Fanapt® and milsaperidone in depressive symptoms and Vanda's ability to execute the planned launch of PONVORY® in the US and ongoing launch of Fanapt®. Therefore, no assurance can be given that the results or developments anticipated by Vanda will be realized or, even if substantially realized, that they will have the expected consequences to, or effects on, Vanda. Forward-looking statements in this press release should be evaluated together with the various risks and uncertainties that affect Vanda's business and market, particularly those identified in the "Cautionary Note Regarding Forward-Looking Statements", "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" sections of Vanda's most recent Annual Report on Form 10-K, as updated by Vanda's subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the U.S. Securities and Exchange Commission, which are available at . All written and verbal forward-looking statements attributable to Vanda or any person acting on its behalf are expressly qualified in their entirety by the cautionary statements contained or referred to herein. Vanda cautions investors not to rely too heavily on the forward-looking statements Vanda makes or that are made on its behalf. The information in this press release is provided only as of the date of this press release, and Vanda undertakes no obligation, and specifically declines any obligation, to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. Corporate Contact: Kevin Moran Senior Vice President, Chief Financial Officer and Treasurer Vanda Pharmaceuticals Inc. 202-734-3400 [email protected] Jim Golden / Jack Kelleher / Dan Moore Collected Strategies [email protected] SOURCE Vanda Pharmaceuticals Inc.

Phase 2Phase 1Phase 3Clinical ResultNDA

07 Feb 2024

·www.prnewswire.com

Vanda Pharmaceuticals Reports Fourth Quarter and Full Year 2023 Financial Results

Full year 2023 revenues were $192.6 million PONVORY® acquisition completed in Q4 2023 and transition ongoing 3 FDA PDUFA target action dates in 2024 Ended 2023 with approximately $388 million in cash and cash equivalents WASHINGTON, Feb. 7, 2024 /PRNewswire/ -- Vanda Pharmaceuticals Inc. (Vanda) (Nasdaq: VNDA) today announced financial and operational results for the fourth quarter and full year ended December 31, 2023. "Despite significant external commercial and regulatory challenges, last year was a landmark year for Vanda, as we supported our commercial programs and, through a transformational deal, we added PONVORY® to our portfolio alongside Fanapt® and HETLIOZ®," said Mihael H. Polymeropoulos, M.D., Vanda's President, CEO and Chairman of the Board. "At the same time, we advanced our clinical development pipeline with three NDA and sNDA submissions for insomnia, bipolar disorder and gastroparesis. Looking forward to this year, we are committed to advancing our clinical development pipeline and strengthening our commercial presence with a portfolio of innovative products serving unmet patient needs." Financial Highlights Fourth Quarter of 2023 Total net product sales from HETLIOZ®, Fanapt® and PONVORY® were $45.3 million in the fourth quarter of 2023, a 30% decrease compared to $64.5 million in the fourth quarter of 2022, and a 17% increase compared to $38.8 million in the third quarter of 2023. HETLIOZ® net product sales were $21.1 million in the fourth quarter of 2023, a 47% decrease compared to $40.1 million in the fourth quarter of 2022, and a 20% increase compared to $17.5 million in the third quarter of 2023. The decrease relative to the fourth quarter of 2022 was the result of the at-risk launch of generic versions of HETLIOZ® in the U.S. Fanapt® net product sales were $22.6 million in the fourth quarter of 2023, a 7% decrease compared to $24.4 million in the fourth quarter of 2022, and a 6% increase compared to $21.3 million in the third quarter of 2023. PONVORY® net product sales were $1.6 million in the fourth quarter of 2023. These net product sales reflect the revenue generated during the period between the product acquisition date of December 7, 2023 and December 31, 2023. Net loss was $2.4 million in the fourth quarter of 2023 compared to net income of $6.9 million in the fourth quarter of 2022, and net income of $0.1 million in the third quarter of 2023. Cash, cash equivalents and marketable securities (Cash) was $388.3 million as of December 31, 2023, representing a decrease to Cash of $101.6 million compared to September 30, 2023. During the period, Vanda completed the acquisition of PONVORY® from Actelion Pharmaceuticals Ltd. (Janssen), a Johnson & Johnson Company, for $100.0 million. Full Year 2023 Total net product sales from HETLIOZ®, Fanapt® and PONVORY® were $192.6 million for the full year 2023, a 24% decrease compared to $254.4 million for the full year 2022. HETLIOZ® net product sales were $100.2 million for the full year 2023, a 37% decrease compared to $159.7 million for the full year 2022. The decrease was the result of the at-risk launch of generic versions of HETLIOZ® in the U.S. Fanapt® net product sales were $90.9 million for the full year 2023, a 4% decrease compared to $94.7 million for the full year 2022. PONVORY® net product sales were $1.6 million for the full year 2023. These net product sales reflect the revenue generated during the period between the product acquisition date of December 7, 2023 and December 31, 2023. Net income was $2.5 million for the full year 2023 compared to net income of $6.3 million for the full year 2022. Cash, cash equivalents and marketable securities (Cash) was $388.3 million as of December 31, 2023, representing a decrease to Cash of $78.6 million, or 17%, compared to December 31, 2022. During the period, Vanda completed the acquisition of PONVORY® from Janssen for $100.0 million. Key Operational Highlights HETLIOZ® (tasimelteon) The supplemental New Drug Application (sNDA) for HETLIOZ® in the treatment of insomnia is under review by the U.S. Food and Drug Administration (FDA) with a Prescription Drug User Fee Act (PDUFA) target action date of March 4, 2024. Vanda announced that on February 4, 2024, it received a notification from the FDA stating that the FDA had identified deficiencies that preclude discussion of labeling and postmarketing requirements/commitments at this time. No deficiencies were disclosed by the FDA in the notification, and the FDA stated that the notification does not reflect a final decision on the information under review. On February 6, 2024, Vanda filed suit in the U.S. District Court for the District of Columbia (D.C. District Court) challenging the FDA's conduct in reviewing the insomnia sNDA. Vanda is asking the D.C. District Court to compel the FDA to adhere to the legally mandated 180-day review period for sNDAs and to declare as unlawful and void the regulations the FDA relies upon to issue complete response letters. Vanda is also continuing to pursue FDA approval for HETLIOZ® in the treatment of jet lag disorder. Vanda announced in January 2024 that the D.C. District Court granted Vanda's motion for summary judgment on its claim against the FDA for unlawfully delaying a hearing on the approvability of Vanda's sNDA for HETLIOZ® in the treatment of jet lag disorder. The D.C. District Court ordered the FDA to either finally resolve Vanda's jet lag sNDA or commence a hearing on the sNDA on or before March 5, 2024. In January 2024, Vanda filed a petition for a writ of certiorari with the U.S. Supreme Court to review the decision of the U.S. Court of Appeals for the Federal Circuit in Vanda's HETLIOZ® Abbreviated New Drug Application (ANDA) litigation against Teva Pharmaceuticals USA, Inc. (Teva), Apotex Inc. and Apotex Corp. (collectively, Apotex). Teva and Apotex have waived their opportunity to respond to Vanda's petition, which is now ripe for decision by the U.S. Supreme Court. Fanapt® (iloperidone) The article "Efficacy and Safety of Iloperidone in Bipolar Mania: A Double-Blind, Placebo-Controlled Study" was published in January 2024 in the Journal of Clinical Psychiatry.1 The findings of this pivotal study have been submitted to the FDA as part of Vanda's sNDA for Fanapt® in the treatment of bipolar I disorder in adults. The sNDA for Fanapt® in the treatment of bipolar I disorder in adults is under review by the FDA with a PDUFA target action date of April 2, 2024. PONVORY® (ponesimod) Vanda completed the acquisition of the U.S. and Canadian rights to PONVORY® from Janssen for $100.0 million in December 2023 and the transition is ongoing. PONVORY® is a once-daily oral selective sphingosine-1-phosphate receptor 1 modulator, approved by the FDA and Health Canada to treat adults with relapsing forms of multiple sclerosis, and is a potential therapeutic candidate for the treatment of a diverse group of inflammatory/autoimmune disorders ranging from psoriasis to ulcerative colitis. Vanda announced in January 2024 that the U.S. Patent and Trademark Office (USPTO) had issued a notice of allowance for its PONVORY® patent application, 17/962,968, covering methods for reducing clinical management events before or during the treatment of multiple sclerosis and methods for reinstating treatment after missed doses. When issued, the patent is anticipated to expire on October 10, 2042. Upon issuance, Vanda intends to list this patent in the FDA publication Approved Drug Products with Therapeutic Equivalence Evaluations, commonly known as the Orange Book. Tradipitant The article "The Efficacy of Tradipitant in Patients with Diabetic and Idiopathic Gastroparesis in Phase III Randomized Placebo-Controlled Clinical Trial" was published in January 2024 in the Clinical Gastroenterology and Hepatology Journal.2 The findings of this pivotal study as well as a previously reported positive placebo-controlled study in diabetic and idiopathic gastroparesis have been submitted to the FDA as part of Vanda's New Drug Application (NDA) for tradipitant in the treatment of symptoms of gastroparesis in adults.3 In December 2023, Vanda announced that the NDA for tradipitant for the treatment of symptoms of gastroparesis was accepted for filing and is under review by the FDA with a PDUFA target action date of September 18, 2024. The second Phase III study of tradipitant in the treatment of motion sickness is over 50% enrolled. In May 2023, Vanda previously announced positive results from its first Phase III study of tradipitant in the treatment of motion sickness. Vanda plans to pursue FDA approval upon completion of the clinical development program. Early-Stage Programs In January 2024, Vanda announced that the FDA had 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), an inherited peripheral neuropathy for which there is no available treatment. In January 2024, Vanda announced that the FDA had also approved the IND to evaluate VTR-297 for the treatment of onychomycosis, a fungal infection of the nail. Other Legal Updates Vanda announced in January 2024 that the United States Court of Federal Claims denied in part the U.S. government's motion to dismiss Vanda's claims against the U.S. for the FDA's uncompensated taking of Vanda's trade secrets and confidential information, thereby allowing Vanda's lawsuit to proceed. Vanda is seeking compensation from the U.S. for the takings it contends occurred through the FDA's improper communication and disclosure of trade secrets and confidential information to certain generic drug manufacturers. Vanda now intends to engage in discovery to support its claims. GAAP Financial Results Net loss was $2.4 million in the fourth quarter of 2023 compared to net income of $6.9 million in the fourth quarter of 2022. Diluted net loss per share was $0.04 in the fourth quarter of 2023 compared to diluted net income per share of $0.12 in the fourth quarter of 2022. Net income was $2.5 million for the full year 2023 compared to net income of $6.3 million for the full year 2022. Diluted net income per share was $0.04 for the full year 2023 compared to diluted net income per share of $0.11 for the full year 2022. 2024 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 generic versions of HETLIOZ®, Vanda is unable to provide 2024 financial guidance at this time. Conference Call Vanda has scheduled a conference call for today, Wednesday, February 7, 2024, at 4:30 PM ET. During the call, Vanda's management will discuss the fourth quarter and full year 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 8053170. A replay of the call will be available on Wednesday, February 7, 2024, beginning at 8:30 PM ET and will be accessible until Wednesday, February 14, 2024 at 11:59 PM ET. The replay call-in number is 1-800-770-2030 for domestic callers and 1-609-800-9909 for international callers. The passcode number is 8053170. The conference call will be broadcast simultaneously on Vanda's website, . Investors should click on the Investors tab and are advised to go to the website at least 15 minutes early to register, download, and install any necessary software or presentations. The call will also be archived on Vanda's website for a period of 30 days. References Torres R, Czeisler EL, Chadwick SR, et al. Efficacy and safety of iloperidone in bipolar mania: a double-blind, placebo-controlled study. J Clin Psychiatry. Carlin, J. L., Polymeropoulos, C., Camilleri, M., Lembo, A., Fisher, M., Kupersmith, C., Madonick, D., Moszczynski, P., Smieszek, S., Xiao, C., Birznieks, G., & Polymeropoulos, M. H. (2024). The efficacy of tradipitant in patients with diabetic and idiopathic gastroparesis in phase III randomized placebo-controlled clinical trial. Clinical Gastroenterology and Hepatology. Carlin, J. L., Lieberman, V. R., Dahal, A., Keefe, M. S., Xiao, C., Birznieks, G., Abell, T. L., Lembo, A., Parkman, H. P., & Polymeropoulos, M. H. (2021). Efficacy and Safety of Tradipitant in Patients with Diabetic and Idiopathic Gastroparesis in a Randomized, Placebo-Controlled Trial. Gastroenterology, 160(1), 76–87.e4. 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 advancement of Vanda's clinical development pipeline and strengthening of its commercial presence, Vanda's plans for pursuit of FDA approval of HETLIOZ® in the treatments of insomnia and jet lag disorder, Fanapt® in the treatment of bipolar I in adults and tradipitant in the treatment of symptoms of gastroparesis and the treatment of motion sickness, Vanda's expectations regarding the timing of the FDA's decisions with respect to the sNDAs for HETLIOZ® and Fanapt® and the NDA for tradipitant, the potential for PONVORY® to treat a diverse group of inflammatory/autoimmune disorders, the USPTO's plans to issue the new PONVORY® patent, the anticipated life of the patent and Vanda's intentions to list the patent in the Orange Book 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 complete the clinical development of the products in its pipeline and obtain regulatory approval and market acceptance of these products, Vanda's ability to obtain FDA approval of the sNDAs for HETLIOZ® and Fanapt® and the NDA for tradipitant, the FDA's ability to meet the PDUFA target action dates for the sNDAs for HETLIOZ® and Fanapt® and the NDA for tradipitant, the FDA's assessment of the sufficiency of the data packages included in Vanda's regulatory submissions for HETLIOZ®, Fanapt® and tradipitant, Vanda's ability to complete the clinical program for tradipitant in the treatment of motion sickness, 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 payment by Vanda to the USPTO of all fees required prior to the issuance of the new PONVORY® patent, the ultimate issuance of the patent by the USPTO and Vanda's ability to protect its intellectual property rights and defend the new PONVORY® patent against any attempt to invalidate it. 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] SOURCE Vanda Pharmaceuticals Inc.

Phase 3NDAAcquisitionDrug ApprovalFinancial Statement

31 Jan 2024

·www.prnewswire.com

Vanda Pharmaceuticals Receives FDA Approval to Proceed with Investigational New Drug VTR-297 a Topical Antifungal Candidate for the Treatment of Onychomycosis

WASHINGTON, Jan. 31, 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 VTR-297 for the treatment of onychomycosis. Onychomycosis, or tinea unguium, is a fungal infection of the nail. Onychomycosis can result in discoloration of the nail, onycholysis (nail separation from the nail bed), and nail plate thickening. Onychomycosis accounts for one half of all nail disease with an estimated U.S. prevalence of up to 14%.1 In addition to cosmetic issues, onychomycosis infection may indirectly decrease peripheral circulation, thereby worsening conditions such as venous stasis and diabetic foot ulcers.2 "The initiation of clinical studies with VTR-297 in the treatment of onychomycosis is an important milestone in studying and developing potential new therapies for this common disorder," said Mihael H. Polymeropoulos, M.D., Vanda's President, CEO and Chairman of the Board. VTR-297 is a small molecule histone deacetylase (HDAC) inhibitor with activity against dermatophytes and fungi, originally isolated from the yeast species Streptomyces hygroscopicus as an antifungal antibiotic, first described in 1976.3 Current therapies for onychomycosis include topical agents JUBLIA® (efinaconzole), KERYDIN® (tavaborole), and PENLAC® (ciclopirox). There have not been any new onychomycosis treatments approved by the FDA since 2014.4 References Centers for Disease Control and Prevention. Fungal Nail Infections. Updated September 13, 2022. Accessed January 30, 2024. Available online: Scher, R. Onychomycosis: a significant medical disorder. J Am Acad Dermatol. 35, S2–5 (1996). Available online: (96)90061-4 Tsuji, N., Kobayashi, M., Nagashima, K., Wakisaka, Y., Koizumi, K. A New Antifungal Antibiotic, Trichostatin. J Antibiot (Tokyo). 1976 Jan;29(1):1-6. Available online: Markham, A. Tavaborole: First Global Approval. Drugs 74, 1555–1558 (2014). Available online: 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 the estimated prevalence of onychomycosis and the development of new antifungals, 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, 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 onychomycosis and onychomycosis cases and the ability to successfully complete the clinical development of, and obtain regulatory approval for, VTR-297 in the treatment of onychomycosis. 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] SOURCE Vanda Pharmaceuticals Inc.

Drug ApprovalIND

100 Deals associated with Trichostatin A

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KEGG	Wiki	ATC	Drug Bank
-	-	-	DB04297

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Indication	Highest Phase	Country/Location	Organization	Date
Hematologic Neoplasms	Phase 2	US	Vanda Pharmaceuticals, Inc.	-
Onychomycosis	IND Approval	US	Vanda Pharmaceuticals, Inc.	31 Jan 2024

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03838926 (ASH2022) Manual	Phase 1	Hematologic Neoplasms	12	Trichostatin A	dohgqkxnhy(heuvjsobwr) = lvdqckmrwn avecewgqnj (biowczmqil )	Positive	15 Nov 2022
ARVO2015	Not Applicable	-	-	TSA (Trichostatin A)	lnxwvcfojx(iussxtsoyy) = eopdeggtqa samvejkilm (txbpbziowj ) View more	-	01 Jun 2015
				Vehicle control	lnxwvcfojx(iussxtsoyy) = wdnalwpbsu samvejkilm (txbpbziowj ) View more
ARVO2011	Not Applicable	Corneal Opacity	-	Trichostatin-A	zzkgjisqqh(irevkazxol) = yqdbpnoskz cjlufrjmys (alwsbeeupx )	-	01 Apr 2011
				Trichostatin-A	zzkgjisqqh(irevkazxol) = busflwwayx cjlufrjmys (alwsbeeupx )

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