Momelotinib Dihydrochloride

WASHINGTON, Dec. 20, 2024 /PRNewswire/ -- Vanda Pharmaceuticals Inc. (Vanda) (Nasdaq: VNDA) today announced the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation for VGT-1849A, a selective antisense oligonucleotide (ASO)-based JAK2 inhibitor for the treatment of polycythemia vera (PV), a form of a rare hematologic malignancy that is estimated to affect 1 in 2000 Americans.1 PV is a chronic myeloproliferative disorder characterized by aberrant hematopoiesis of myeloid lineage with exuberant red cell production and increased release of pro-inflammatory cytokines. More than 95% of PV patients harbor the JAK2 V617F gain-of-function mutation leading to aberrant JAK2 production.2 Inhibiting JAK2 acts to suppress hematopoiesis, consequently reducing red blood cell, neutrophil, platelet, and lymphocyte production. JAK2 inhibitors have been shown to be efficacious in treating various JAK-dependent hematologic malignancies, including the treatment of PV. By selective reduction of JAK2 levels, the ASO VGT-1849A has the potential to reduce JAK2V617F-driven pathogenic signaling, ultimately suppressing the malignant proliferation and survival of hematopoietic cells. Currently available small molecule inhibitors targeting the JAK2 protein kinase, such as Jakafi®, Inrebic®, Ojjaara®, and Vonjo®, lack sole selectivity for the target protein, which can result in off target effects. The adverse side effects that may occur from JAK inhibition emphasize the importance of selectively targeting JAK2 while avoiding inhibition of other JAK family members. By specifically targeting JAK2, Vanda seeks to reduce the risk of infection and toxic effects that are seen with inhibitors also blocking JAK1, JAK3, TYK2, or other kinases outside of the JAK family. If approved, VGT-1849A could offer targeted efficacy with an improved safety profile and convenient dosing. "This orphan designation for VGT-1849A is an important milestone in precision medicine-based therapeutics in the space of hematological malignancies. This milestone marks the second precision medicine therapeutic for Vanda following the development of VCA-894A for Charcot-Marie-Tooth3 that is expected to begin clinical testing in the coming months," said Mihael H. Polymeropoulos, M.D., Vanda's President, CEO and Chairman of the Board. VGT-1849A is a novel ASO treatment candidate for PV and other JAK2-driven hematologic malignancies. By selectively targeting JAK2, VGT-1849A reduces downstream signaling and JAK2V617F-driven autonomous cell proliferation, without any off-target kinase effects. The ability of VGT-1849A to reduce JAK2 activity may alleviate the disease burden that patients with PV face with a favorable safety profile, resulting in a higher quality of life for patients. Orphan Drug Designation is granted by the FDA to investigational therapies addressing rare medical conditions and provides benefits to drug developers. References: Grunwald, M. R.; Stein, B. L.; Boccia, R. V.; Oh, S. T.; Paranagama, D.; Parasuraman, S.; Colucci, P.; Mesa, R. Clinical and Disease Characteristics From REVEAL at Time of Enrollment (Baseline): Prospective Observational Study of Patients With Polycythemia Vera in the United States. Clin Lymphoma Myeloma Leuk 2018, 18 (12), 788-795.e2. . P. Gou, W. Zhang, and S. Giraudier, "Insights into the Potential Mechanisms of JAK2V617F Somatic Mutation Contributing Distinct Phenotypes in Myeloproliferative Neoplasms," Myeloproliferative Neoplasms. Int. J. Mol. Sci, vol. 2022, p. 1013, 2022, S. Smieszek, C. Tyner, A. Kaden, C. Johnson, C. Polymeropoulos, G. Birznieks, M. Polymeropoulos. Potential treatment for CMT2S caused by IGHMBP2 cryptic splice variant, with ASO based therapeutic [abstract]. Mov Disord. 2023; 38 (suppl 1). . 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. About VGT-1849A VGT-1849A is an antisense oligonucleotide (ASO) that selectively targets JAK2, reducing increased activity of JAK2 that may cause hematologic malignancies. ASOs have broad applicability in addressing a number of disorders caused by genetic variants. CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS Various statements in this press release, including, but not limited to statements regarding the estimated prevalence of PV, the potential therapeutic effects of VGT-1849A, the timing of the initiation of clinical testing of VCA-894A and the potential benefits of VGT-1849A, 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 PV cases, the ability of VGT-1849A to safely and effectively treat PV, Vanda's ability to begin clinical testing of VCA-894A during the specified timeframe and Vanda's ability to successfully complete the clinical development of, and obtain regulatory approval for, VGT-1849A in the treatment of PV. There can be no assurance that the actual 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. Therefore, no assurance can be given that the outcomes stated in such forward-looking statements and estimates will be achieved. 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 Annual Report on Form 10-K for the fiscal year ended December 31, 2023, 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. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Latest results in Phase 1/2 studies show promise for two investigational treatments for patients with relapsed/refractory blood and bone marrow cancers Nuvisertib (TP-3654), an investigational oral small molecule highly selective PIM1 kinase inhibitor, is being evaluated in a Phase 1/2 study in patients with relapsed/refractory myelofibrosis Enzomenib (DSP-5336), an investigational, oral small molecule designed to inhibit the menin and KMT2A protein interaction, is being evaluated in a Phase 1/2 study in patients with relapsed/refractory acute leukemia MARLBOROUGH, Mass., Dec. 9, 2024 /PRNewswire/ -- Sumitomo Pharma America, Inc. (SMPA) today presented new clinical data supporting further development of nuvisertib, an investigational small molecule being researched for the treatment of relapsed/refractory myelofibrosis (MF), and enzomenib, an investigational oral small molecule being researched for relapsed/refractory acute leukemia, at the 66th American Society of Hematology (ASH) Annual Meeting & Exposition. Preliminary data presented from the ongoing Phase 1/2 study of nuvisertib monotherapy (N=74) in patients with relapsed/refractory MF show nuvisertib was well tolerated with no dose-limiting toxicities (DLTs). Preliminary data in evaluable patients showed clinical activity including spleen volume reduction (SVR25 of 22.2%), symptom reduction (TSS50 of 44.4%), and bone marrow fibrosis (47.8% patients) and hemoglobin (25% patients) and platelet count (27.6% patients) improvement. Additional data presented show nuvisertib treatment led to significant cytokine modulation (e.g. EN-RAGE, IL-18, MIP-1β, and adiponectin) over time correlating with spleen and symptom responses. The global study has been expanded to evaluate nuvisertib add-on to ruxolitinib, the first approved Janus-associated kinase (JAK) inhibitor, and in combination with momelotinib, a recently approved JAK inhibitor for MF patients with anemia, to assess safety and potential clinical activity. New preliminary clinical and translational data from the enzomenib Phase 1/2 study were also presented at the conference by Dr. Joshua Zeidner from the University of North Carolina. The safety population included 84 total patients with acute leukemia, most of whom (94%, 79/84) had acute myeloid leukemia (AML). The study population was diverse, with 47.6% non-white (40/84), and also heavily pre-treated, with a median of 3 prior regimens. In these patients, enzomenib was administered twice daily in continuous 28-day study cycles at dose levels from 40 mg BID up to 300 mg BID. Enzomenib was well tolerated with low overall rates of drug-related adverse events and no dose limiting toxicity (DLT) reported. Differentiation syndrome was reported in 10.7% of patients but did not result in patient deaths nor did it require permanent discontinuations of enzomenib. Also presented were clinical activity results from the dose optimization cohorts at the dose levels of 200 mg BID and 300 mg BID. The data included results from all patients with KMT2A rearrangement (KMT2Ar) or NPM1 mutation (NPM1m) who had received at least one dose of enzomenib and who had not received a menin inhibitor previously. In 23 patients with KMT2Ar, the Objective Response Rate (ORR) using ELN 2017 criteria was 65.2% (15/23) and the proportion to achieve CR+CRh was 30.4% (7/23). In the subset of patients with KMT2Ar to receive 300 mg BID (n = 15), the ORR was 73.3% (11/15) and CR+CR was 40% (6/15). In the 17 total patients with NPM1 mutation (NPM1m) who received 200 mg BID or 300 mg BID, the ORR was 58.8% (10/17) and the proportion to achieve CR+CRh was 47.1% (8/17). The 400 mg BID dose optimization cohort is ongoing, with 21 patients enrolled as of the clinical cut-off and data planned for presentation at a future conference. These encouraging clinical activity results combined with an excellent safety profile suggest that enzomenib may play an important role in the treatment of patients with relapsed/refractory acute leukemia with KMT2A rearrangement or NPM1 mutation. "These data signal growing momentum in our oncological pipeline and an important milestone in our development of new treatments for relapsed/refractory MF and acute leukemia," said Tsutomu Nakagawa, Ph.D., President and Chief Executive Officer of SMPA. "With these promising results in hand, we remain committed to advancing nuvisertib and enzomenib as we believe our investigational therapies may have the potential to improve the lives of patients living with these critical cancers who do not respond to currently available therapeutics." MF is a rare type of blood cancer that is characterized by the buildup of fibrous tissue in the bone marrow, which can affect the production of blood cells. This buildup is caused by a dysregulation in the JAK signaling pathway. MF is a serious and rare disease with 0.7 new cases per 100,000 people worldwide each year.4 Leukemia is a type of cancer that forms in blood-forming tissue, characterized by the uncontrolled growth of blood cells, usually white blood cells, in the bone marrow. Acute leukemia, a form of leukemia, requires immediate treatment as blood cells multiply rapidly leading to a sudden onset of symptoms.1 Approximately 30% of AML patients have NPM1 mutations2 and 5-10% of AML patients have KMT2A (MLL) rearrangements.3 "Patients and families living with incurable cancers of MF and AML are in need of new treatment options – and we are encouraged by the promising clinical activity for both nuvisertib and enzomenib," said Jatin Shah, M.D., Chief Medical Officer, Oncology, SMPA. "This additional preliminary data reinforces the strong potential for PIM1 inhibition in myelofibrosis, and for menin inhibitors in acute leukemia." About enzomenib (DSP-5336) Enzomenib (DSP-5336) is an investigational small molecule inhibitor of the menin and mixed-lineage leukemia (MLL) protein interaction. Menin is a scaffold nuclear protein which plays key roles in gene expression and protein interactions involved in many biological pathways, including cell growth, cell cycle, genomic stability, and hematopoiesis.5,6 In preclinical studies, enzomenib has shown selective growth inhibition in human acute leukemia cell lines with KMT2A (MLL) rearrangements or NPM1 mutations.5,7 Enzomenib reduced the expression of the leukemia-associated genes HOXA9 and MEIS1, and increased the expression of the differentiation gene CD11b in human acute leukemia cell lines with MLL rearrangements and NPM1 mutation.8,9 The safety and efficacy of enzomenib is currently being clinically evaluated in a Phase 1/2 dose escalation/dose expansion study in patients with relapsed or refractory acute leukemia (NCT04988555). The FDA granted Orphan Drug Designation for enzomenib for the indication of acute myeloid leukemia in June 2022. The FDA granted Fast Track Designation for enzomenib for the indication of relapsed or refractory acute myeloid leukemia with MLLr or NPM1m in June 2024. The PMDA granted Orphan Drug Designation for enzomenib for the indication of relapsed or refractory acute myeloid leukemia with MLLr or NPM1m in September 2024. About nuvisertib (TP-3654) Nuvisertib (TP-3654) is an oral investigational selective inhibitor of PIM1 kinase, which has shown potential antitumor and antifibrotic activity through multiple pathways, including induction of apoptosis in preclinical models.10,11 Nuvisertib was observed to inhibit proliferation and induce apoptosis in murine and human hematopoietic cells expressing the clinically relevant JAK2V617F mutation.10 Nuvisertib alone and in combination with ruxolitinib showed white blood cell and neutrophil count normalization, and also reduced spleen size and bone marrow fibrosis in JAK2V617F and MPLW515L murine models of myelofibrosis.11 The safety and efficacy of nuvisertib is currently being clinically evaluated in a Phase 1/2 study in patients with intermediate and high-risk myelofibrosis (NCT04176198). The U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation for nuvisertib for the indication of myelofibrosis in May 2022. The PMDA granted Orphan Drug Designation for nuvisertib for the indication of myelofibrosis in November 2024. About Sumitomo Pharma Sumitomo Pharma Co., Ltd. is a global pharmaceutical company based in Japan with key operations in the U.S. (Sumitomo Pharma America, Inc.), Canada (Sumitomo Pharma Canada, Inc.) and Europe (Sumitomo Pharma Switzerland GmbH) focused on addressing patient needs in oncology, urology, women's health, rare diseases, psychiatry & neurology, and cell & gene therapies. With several marketed products in the U.S., Canada, and Europe, a diverse pipeline of early- to late-stage assets, we aim to accelerate discovery, research, and development to bring novel therapies to patients sooner. For more information on SMPA, visit our website or follow us on LinkedIn. SUMITOMO PHARMA is a trademark of Sumitomo Pharma Co., Ltd., used under license. Sumitomo Pharma America, Inc. is a U.S. subsidiary of Sumitomo Pharma Co., Ltd. © 2024 Sumitomo Pharma America, Inc. All rights reserved. References Chennamadhavuni A, Lyengar V, Mukkamalla SKR, et al. Leukemia. [Updated 2023 Jan 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: . Brandi ML, Agarwal SK, Perrier ND, Lines KE, Valk GD, Thakker RV. Multiple Endocrine Neoplasia Type 1: Latest Insights. Endocr Rev. 2021;42(2):133-170. doi:10.1210/endrev/bnaa031 Borkin D, Klossowski S, Pollock J, et al. Complexity of Blocking Bivalent Protein-Protein Interactions: Development of a Highly Potent Inhibitor of the Menin-Mixed-Lineage Leukemia Interaction. J Med Chem. 2018;61(11):4832-4850. doi:10.1021/acs.jmedchem.8b00071. Hernández-Boluda J-C, Czerw T. Transplantation Algorithm for Myelofibrosis in 2022 and Beyond. Best Practice & Research Clinical Haematology. June 2022, 101369. doi: 10.1016/j.beha.2022.101369 Cierpicki T, Grembecka J. Challenges and opportunities in targeting the menin-MLL Interaction. Future Med Chem. 2014; 6(4):447-462. doi:10.4155/fmc.13.214. Matkar S, Thiel A, Hua X. Menin: a scaffold protein that controls gene expression and cell signaling. Trends Biochem Sci. 2013; 38(8):394-402. doi:10.1016/j.tibs.2013.05.005. Kuhn MWM, Song E, Feng Z, et al. Targeting chromatin regulators inhibits leukemogenic gene expression in NPM1 mutant leukemia. Cancer Discov. 2016;6(10):1166-1181. doi:10.1158/2159-8290.CD-16-0237. Eguchi K, Shimizu T, Kato D, et al. Preclinical Evaluation of a Novel Orally Bioavailable Menin-MLL Interaction Inhibitor, DSP-5336, for the Treatment of Acute Leukemia Patients with MLL-Rearrangement or NPM1 Mutation. Blood 2021; 138 (Supplement 1): 3339. Available at: . Daver N, Zeidner JF, Yuda J, et al. Phase 1/2 First-in-Human Study of the Menin-MLL Inhibitor DSP-5336 in Patients with Relapsed or Refractory Acute Leukemia. Blood 2023; 142 (Supplement 1): 2911. Available at: . Foulks JM, Carpenter KJ, Luo B, et al. A small-molecule inhibitor of PIM kinases as a potential treatment for urothelial carcinomas. Neoplasia. 2014;16(5):403-412. Dutta A., Nath D, Yang Y, et al. Genetic ablation of Pim1 or pharmacologic inhibition with TP-3654 ameliorates myelofibrosis in murine models. Leukemia. 2022; 36 (3): 746-759. doi: 10.1038/s41375-021-01464-2. For a copy of this release, visit Sumitomo Pharma America's website at . SOURCE Sumitomo Pharma America WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED