Last update 01 Nov 2024

JBI-802

Last update 01 Nov 2024

Overview

R&D Status

Clinical Result

Translational Medicine

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

LSD1/HDAC6 dual inhibitors, Lysine specific demethylase 1 and histone deacetylase 6 inhibitors, N-hydroxy-4-((4-((((1R,2S)-2-phenylcyclopropyl) amino)methyl)-1H-pyrazol-1-yl)methyl)benzamide hydrogen bromide.

+ [2]

Target

HDAC6 x KDM1A

Mechanism

HDAC6 inhibitors(Histone deacetylase 6 inhibitors), KDM1A inhibitors(Lysine-specific histone demethylase 1 inhibitors)

Therapeutic Areas

NeoplasmsHemic and Lymphatic DiseasesRespiratory Diseases

Active Indication

Locally Advanced Malignant Solid NeoplasmMetastatic Solid TumorSmall Cell Lung Cancer+ [5]

Inactive Indication-

Originator Organization

Jubilant Therapeutics, Inc.Startup

Active Organization

Jubilant Therapeutics, Inc.Startup

Inactive Organization-

Drug Highest PhasePhase 1/2

First Approval Date-

RegulationOrphan Drug (US)

Structure

Molecular FormulaC21H22N4O2

InChIKeyVLTIYMVMEIUCSB-VQTJNVASSA-N

CAS Registry2982787-49-3

Clinical Trials associated with JBI-802

ACTRN12624000478516 / Not yet recruitingPhase 1/2

Study to Assess Safety and Preliminary Efficacy of Orally Administered JBI-802 in Subjects with Myeloproliferative Neoplasms (MPN) and Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN) with Thrombocytosis

Start Date29 Apr 2024

Sponsor / Collaborator

Jubilant Therapeutics, Inc.Startup

[+1]

NCT05268666 / RecruitingPhase 1/2

A First-in-Human, Open-label, Dose Escalation and Expansion Study of Orally Administered JBI-802 in Patients With Advanced Solid Tumors

The purpose of this study is to determine the maximum-tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of JBI-802 in patients with Advanced Solid Tumors.The efficacy of the RP2D will be evaluated in phase 2 in patients with solid tumors of neuroendocrine differentiation.

Start Date08 Apr 2022

Sponsor / Collaborator

Jubilant Therapeutics, Inc.Startup

100 Clinical Results associated with JBI-802

100 Translational Medicine associated with JBI-802

100 Patents (Medical) associated with JBI-802

Literatures (Medical) associated with JBI-802

10 Oct 2024·Journal of Medicinal Chemistry

Syntheses of LSD1/HDAC Inhibitors with Demonstrated Efficacy against Colorectal Cancer: In Vitro and In Vivo Studies Including Patient-Derived Organoids

Article

Author: Wu, Yi-Wen ; Liou, Jing-Ping ; Tsai, Kelvin K. ; Cheng, Li-Hsin ; Chen, Mei-Chuan ; Nepali, Kunal ; Ho, Hsiu-O ; Lai, Mei-Jung ; Pan, Shiow-Lin ; Chou, Po-Yu

Precedential evidence ascertaining the overexpression of LSD1 and HDACs in colorectal cancer spurred us to design a series of dual LSD1-HDAC inhibitors. Capitalizing on the modular nature of the three-component HDAC inhibitory model, tranylcypromine as a surface recognition motif was appended to zinc-binding motifs via diverse linkers. A compendium of hydroxamic acids was generated and evaluated for in vitro cytotoxicity against HCT-116 cells (human colorectal cancer cell lines). The most potent cell growth inhibitor 2 (GI₅₀ = 0.495 μMm HCT-116 cells) shows promising anticancer effects by reducing colony formation and inducing cell cycle arrest in HCT-116 cells. It exhibits preferential inhibition of HDAC6, along with potent inhibition of LSD1 compared to standard inhibitors. Moreover, Compound 2 upregulates acetyl-tubulin, acetyl-histone H3, and H3K4me2, indicative of LSD1 and HDAC inhibition. In vivo, it demonstrates significant antitumor activity against colorectal cancer, better than irinotecan, and effectively inhibits growth in patient-derived CRC organoids.

25 Jan 2024·Journal of Medicinal ChemistryQ1 · MEDICINE

Combination Therapy and Dual-Target Inhibitors Based on LSD1: New Emerging Tools in Cancer Therapy

Q1 · MEDICINE

Review

Author: Hou, Wen-Qing ; Wang, Shu-Wu ; Ji, Shi-Kun ; Liu, Hong-Min ; Wang, Shao-Peng ; Shen, Liang ; Wang, Bo ; Dai, Xing-Jie ; Fu, Meng-Jie

Lysine specific demethylase 1 (LSD1), a transcriptional modulator that represses or activates target gene expression, is overexpressed in many cancer and causes imbalance in the expression of normal gene networks. Over two decades, numerous LSD1 inhibitors have been reported, especially some of which have entered clinical trials, including eight irreversible inhibitors (TCP, ORY-1001, GSK-2879552, INCB059872, IMG-7289, ORY-2001, TAK-418, and LH-1802) and two reversible inhibitors (CC-90011 and SP-2577). Most clinical LSD1 inhibitors demonstrated enhanced efficacy in combination with other agents. LSD1 multitarget inhibitors have also been reported, exampled by clinical dual LSD1/histone deacetylases (HDACs) inhibitors 4SC-202 and JBI-802. Herein, we present a comprehensive overview of the combination of LSD1 inhibitors with various antitumor agents, as well as LSD1 multitarget inhibitors. Additionally, the challenges and future research directionsare also discussed, and we hope this review will provide new insight into the development of LSD1-targeted anticancer agents.

01 Feb 2023·Molecular Informatics

Inhibitor Assessment against the LpxC Enzyme of Antibiotic‐resistant Acinetobacter baumannii Using Virtual Screening, Dynamics Simulation, and in vitro Assays

Article

Author: Messaoudi, Abdelmonaem ; Sadfi‐Zouaoui, Najla ; Zoghlami, Manel ; Oueslati, Maroua ; Basharat, Zarrin

AbstractBackground: Bacterial resistance is currently a significant global public health problem. Acinetobacter baumannii has been ranked in the list of the World Health Organization as the most critical and priority pathogen for which new antibiotics are urgently needed. In this context, computational methods play a central role in the modern drug discovery process. The purpose of the current study was to identify new potential therapeutic molecules to neutralize MDR A. baumannii bacteria. Methods: A total of 3686 proteins retrieved from the A. baumannii proteome were subjected to subtractive proteomic analysis to narrow down the spectrum of drug targets. The SWISS‐MODEL server was used to perform a 3D homology model of the selected target protein. The SAVES server was used to evaluate the overall quality of the model. A dataset of 74500 analogues retrieved from the PubChem database was docked with LpxC using the AutoDock software. Results: In this study, we predicted a putative new inhibitor for the Lpxc enzyme of A. baumannii. The LpxC enzyme was selected as the most appropriate drug target for A. baumannii. According to the virtual screening results, N‐[(2S)‐3‐amino‐1‐(hydroxyamino)‐1‐oxopropan‐2‐yl]‐4‐(4‐bromophenyl) benzamide (CS250) could be a promising drug candidate targeting the LpxC enzyme. This molecule shows polar interactions with six amino acids and non‐polar interactions with eight other residues. In vitro experimental validation was performed through the inhibition assay. Conclusion: To the best of our knowledge, this is the first study that suggests CS250 as a promising inhibitory molecule that can be exploited to target this gram‐negative pathogen.

News (Medical) associated with JBI-802

25 Oct 2024

·www.prnewswire.com

Jubilant Therapeutics Inc. announces First Patient Dosing in Global Clinical Trials for JBI-802, a CoREST Inhibitor and JBI-778, a PRMT5 Inhibitor

JBI-802 is a first-in-class, orally administered, inhibitor of CoREST complex JBI-778 is a potential best-in-class, orally administered, brain penetrant inhibitor of PRMT5 MORRISVILLE, N.C., Oct. 25, 2024 /PRNewswire/ -- Jubilant Therapeutics Inc., a biopharmaceutical company advancing small molecule precision therapeutics to address unmet medical needs in oncology and autoimmune diseases, today announced the dosing of first patients in global clinical trials involving two pipeline programs: Phase I/II clinical trial of JBI-802 in heme-oncology and Phase I clinical trial for JBI-778 in solid tumors. "We are excited to take this significant step forward in our mission to transform the lives of patients through the development of easy to administer precision oral medicines with enhanced safety and therapeutic efficacy," said Hari S Bhartia, Chairman, Jubilant Therapeutics Inc. JBI-802 is a first-in-class, orally administered, small-molecule dual inhibitor of LSD1 (Lysine-specific histone demethylase 1A) and HDAC6 (Histone deacetylase 6) within the CoREST (Co-repressor of Repressor Element-1 Silencing Transcription) complex. In the earlier Phase I study conducted in advanced solid tumor patients, JBI-802 showed a dose-proportional increase in exposure across cohorts and a strong correlation between exposure and the on-target effect of platelet decrease. There were no reports of Dysgeusia and Anemia, typical adverse events seen with LSD1only inhibitors. The Phase I trial also showed anti-tumor activity in Non-Small Cell Lung Cancer (NSCLC) patients including a confirmed partial response. Overall, the study results provided human proof-of-principle for expanding the development of JBI-802 in Essential Thrombocythemia and Myelodysplastic Syndrome/Myeloproliferative Neoplasms (MDS/MPN) with thrombocytosis. Essential Thrombocythemia is a chronic disease of excessive platelets with over 100,000 patients in the United States for whom the primary treatment is hydroxyurea, a therapy that poses severe limitations for patients in terms of both safety and efficacy. The second clinical trial is to assess both safety and the recommended Phase II dose for JBI-778, an oral brain-penetrant inhibitor of PRMT5 (Protein arginine N-methyltransferase 5) in mEGFR Tyrosine Kinase Inhibitor (TKI) resistant NSCLC, IDH+ high-grade glioma (HGG) and Adenoid Cystic Carcinoma (ACC). PRMT5, although a proven pathway for multiple cancers, has produced mixed results in terms of drug development due to safety concerns surrounding SAM competitive approach to PRMT5 inhibition and patient segment limitations of MTAP null tumor-focused approach PRMT5 inhibition. JBI-778 is a unique substrate competitive brain penetrant PRMT5 inhibitor that has shown no adverse effects in preclinical setting and can address both MTAP null and wild type tumors as well as brain tumors, catering to a larger patient segment including those with brain metastases. "The two most advanced novel drug candidates at Jubilant Therapeutics Inc. were discovered in-house using our TIBEO (Therapeutic Index and Brain Exposure Optimization) Discovery Engine. It is our unique approach of structure-based drug design to generate novel pharmacophores with improved therapeutic index compared to existing agents. We are excited to advance both JBI-802 and JBI-778 in genetically-defined subsets of patients with select hematological and solid tumor indications with high unmet medical needs. Initial clinical data are expected to read out in 2025," said Syed Kazmi, Chief Executive officer, Jubilant Therapeutics Inc. About JBI-802 JBI-802 is novel, oral, potent and selective dual inhibitor of two epigenetic targets of the CoREST complex: LSD1 and HDAC6. It targets stem cell modulation by inhibiting LSD1 and modulates immune suppression with isoform selective HDAC6 inhibition. Preclinical research has demonstrated its synergistic anti-tumor activity, which is superior compared to either target alone and with a favorable safety profile. JBI-802 is under evaluation in both hematological cancers such as acute myeloid leukemia, myelodysplastic syndrome and other myeloproliferative cancers as well as solid tumors, such as non-small cell lung cancer and small cell lung cancer. About JBI-778 JBI-778 is novel, oral, potent and brain penetrant inhibitor of PRMT5. JBI-778 targets the substrate site and stabilizes SAM bound to PRMT5, providing high biological selectivity and has shown a superior safety profile as seen in animals. Preclinical research has demonstrated significant activity in Tyrokinase-Inhibitor resistant cell lines, brain tumor and NSCLC. JBI-778 is under evaluation in solid tumors such as NSCLC, High Grade Glioma and Adenoid Cystic Carcinoma. About Jubilant Therapeutics Inc. Jubilant Therapeutics Inc. is a clinical stage biopharmaceutical company developing precision oral medicines with enhanced therapeutic index to address unmet medical needs in oncology and autoimmune diseases for genetically defined patients. Its advanced structure-based discovery engine, TIBEO (Therapeutic Index and Brain Exposure Optimization), has been validated through successful partnerships. The Company's clinical pipeline consists of a first-in-class dual CoREST modifier, JBI-802, currently in a Phase I/II clinical trial in multiple tumors and a novel brain-penetrant modulator of PRMT5, currently in Phase I clinical trial. Additional pre-clinical programs include brain penetrant and gut restrictive PDL1 inhibitors, as well as PAD4 inhibitors for oncology and inflammatory indications. The Company is headquartered in Pennsylvania and guided by globally renowned scientific advisors. For more information, please visit or follow us on Twitter @JubilantTx and LinkedIn. Logo: SOURCE Jubilant Therapeutics Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 1Clinical Result

08 Jan 2024

·www.biospace.com

JBI-802 initial Phase I data suggests therapeutic potential in sensitizing immunotherapy resistant tumors and in Myeloproliferative Neoplasms with thrombocytosis

BEDMINSTER, N.J., Jan. 8, 2024 /PRNewswire/ -- Jubilant Therapeutics Inc., a clinical-stage biotechnology company pioneering the development of a first-in-class CoREST (Co-repressor of Repressor Element-1 Silencing Transcription) inhibitor JBI-802 with the dual activity on LSD1 and HDAC6, today announced preliminary safety, pharmacokinetic and initial efficacy results of the Phase I trial in advanced cancer patients. Furthermore, the study results provide a human proof of principle for expanding the development of JBI-802 in Essential Thrombocythemia (ET) and related Myeloproliferative Neoplasms (MPN/MDS) with thrombocytosis. The data from first 11 patients with advanced cancer revealed a dose-proportional increase in exposure across cohorts and a strong correlation between the exposure and the on-target effects of platelet decrease, indicating that pharmacological relevant level of LSD1 inhibition have been achieved. At the same time, platelet decrease is the only adverse event above grade 1 observed in these patients, which differentiates JBI-802 from LSD1-only inhibitors. Specifically, no AEs (Adverse Events) of anemia has been observed, which is potentially due to the positive benefit of inhibition of HDAC6 in erythrocytes. Also, there are no reports of Dysgeusia, an adverse event that has been observed with LSD1-only inhibitors. Among the 11 patients, two were NSCLC (Non-small Cell Lung Cancer) patients, both had progressed on doublet immunotherapy, nivolumab+ipilimumab as first line treatment and both showed anti-tumor activity. Both the patients were treated at lower dose level (10mg) where no relevant decrease of platelets is seen, suggesting that in patients with sensitive tumors this dose can be pharmacologically active with a desirable safety profile. Both NSCLC patients had failed first line treatment with doublet immunotherapy, nivoluman/ipilumab prior to enrolling in the JBI-802 study. The first patient had a STK11 mutation, known to decrease the effectiveness of immunotherapy, present in around 10% of NSCLC patients (higher frequency in lung adenocarcinoma). JBI-802 showed a confirmed partial response in this IO-refractory NSCLC patient with a 39% decrease in the target lung tumor mass. The tumor shrinkage outcome was accompanied by a complete resolution of pancoast syndrome (lung lesion affecting the nerves of brachial plexus). The response appears to be durable after nine cycles and the patient remains on JBI-802 therapy. The second patient had both lung lesion and liver metastasis, which are known to confer resistance to immunotherapy and lead to poor prognosis. Treatment with JBI-802 resulted in over 50% shrinkage of the patient's liver metastasis and a complete resolution of related portal hypertension, edema and improvement of quality of life. Dr. Alexander Starodub, The Christ Hospital - Cincinnati, treating physician for the above patients commented, "The anti-tumor activity seen in these two NSCLC patients is remarkable given the poor prognosis based on their genetic and metastatic pattern. The 10 mg dose of JBI-802 was well-tolerated without any clinically significant adverse effects and the initial clinical data suggest a good therapeutic index for JBI-802." Preclinical studies showed a synergistic anti-tumor effect by combining immunotherapy and JBI-802 in xenograft models. In addition, the CoREST inhibition was reported to sensitize immunotherapy resistant tumors, especially those with STK11 mutations. Taken together, the preliminary efficacy data from the JBI-802 Phase I study suggest the opportunity that a combination between immunotherapy and JBI-802 could bring a new therapy option to such patient populations with limited treatment options. In addition, the on-target dose/exposure-proportional decrease in platelet constitute a proof-of-principle that JBI-802 can be an active compound in hematological malignancies like Essential Thrombocythemia (ET) and other MPN/ MDS characterized by thrombocytosis. A follow up Phase I/II study in MPN/ET and MPN/MDS with thrombocytosis is being planned for early next year to investigate JBI-802 as potential novel treatment option. About Jubilant Therapeutics Inc. Jubilant Therapeutics Inc. is a clinical stage biopharmaceutical company developing precision oral medicines with enhanced therapeutic index to address unmet medical needs in oncology and autoimmune diseases for genetically defined patients. Its advanced structure-based discovery engine, TIBEO (Therapeutic Index and Brain Exposure Optimization), has been validated through successful partnerships including with Blueprint Medicines for a brain penetrant EGFR Exon-20 program. The Company's pipeline consists of a first in class dual coREST modifier, JBI-802, currently in a Phase I/II clinical trial in multiple tumors, a novel brain-penetrant modulator of PRMT5 for which an IND has been accepted, brain penetrant and gut restrictive PDL1 inhibitors, as well as PAD4 inhibitors for oncology and inflammatory indications. The Company is headquartered in Bedminster, New Jersey and guided by globally renowned scientific advisors. For more please visit: Twitter @JubilantTx, LinkedIn Photo: Logo:

Clinical ResultImmunotherapyPhase 1

15 Jun 2023

·www.prnewswire.com

Jubilant Therapeutics Inc. Appoints Nadir Patel as an Independent Member of Its Board of Directors

BEDMINSTER, N.J., June 15, 2023 /PRNewswire/ -- Jubilant Therapeutics Inc., a clinical stage biopharmaceutical company advancing small molecule precision therapeutics to address unmet medical needs in oncology and autoimmune diseases, today announced the appointment of Nadir Patel as an independent director on the Company's Board of Directors. "Nadir Patel has had a distinguished career advising corporate executives in private industry and representing Canada in foreign affairs," said Hari S Bhartia, Chairman, Jubilant Therapeutics Inc . "His broad experience in strategic planning, finance, human resources and other disciplines will be invaluable as Jubilant Therapeutics Inc. continues to develop as a company and advances its differentiated drug pipeline in preclinical and clinical development." Nadir Patel is a senior strategic advisor at global law firm Norton Rose Fulbright Canada LLP, managing director at Fairfax Consulting Services and strategic advisor to the President of Huron University at Western. Prior to his current roles, Nadir held several senior government positions over a notable career in Canada's public service. Most recently, he served as Canada's High Commissioner for the Republic of India, with concurrent accreditation as Canada's Ambassador to Nepal and Ambassador to the Kingdom of Bhutan until 2021. He also previously served as Assistant Deputy Minister and Chief Financial Officer for Canada's Department of Foreign Affairs, Trade and Development and as Canada's Consul General in Shanghai. He currently serves on the board of directors of Canadian Tire Corporation where he also chairs the audit committee, as well as board Chairman at Canadian Tire Jumpstart Charities. Nadir Patel holds a joint MBA from New York University's Stern School of Business, London School of Economics and Political Science, and HEC (Paris) School of Management. About Jubilant Therapeutics Inc. Jubilant Therapeutics Inc. is a clinical stage biopharmaceutical company developing precision oral medicines with enhanced therapeutic index to address unmet medical needs in oncology and autoimmune diseases for genetically defined patients. Its advanced structure-based discovery engine, TIBEO (Therapeutic Index and Brain Exposure Optimization), has been validated through successful partnerships including with Blueprint Medicines for a brain penetrant EGFR Exon-20 program. The Company's pipeline consists of a first in class dual coREST modifier, JBI-802, currently in a Phase I/II clinical trial in multiple tumors, a novel brain-penetrant modulator of PRMT5 for which an IND has been accepted, brain penetrant and gut restrictive PDL1 inhibitors, as well as PAD4 inhibitors for oncology and inflammatory indications. The Company is headquartered in Bedminster, New Jersey and guided by globally renowned scientific advisors. For more please visit: Twitter @JubilantTx, LinkedIn Logo: SOURCE Jubilant Therapeutics Inc.

Executive Change

100 Deals associated with JBI-802

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Locally Advanced Malignant Solid Neoplasm	Phase 2	US	Jubilant Therapeutics, Inc.Startup	08 Apr 2022
Metastatic Solid Tumor	Phase 2	US	Jubilant Therapeutics, Inc.Startup	08 Apr 2022

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05268666 (PRNewswire) Manual	Phase 1	Non-Small Cell Lung Cancer \| Advanced cancer	11	JBI-802	(axbzekssxz) = Platelet decrease is the only adverse event above grade 1 observed in these patients, no AEs (Adverse Events) of anemia has been observed, which is potentially due to the positive benefit of inhibition of HDAC6 in erythrocytes. Also, there are no reports of Dysgeusia, an adverse event that has been observed with LSD1-only inhibitors. zlowoxoece (zhgjczzgum )	Positive	08 Jan 2024
				JBI-802 (NSCLC)

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JBI-802

Overview

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Translational Medicine

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