PAD4

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:

Partial recovery after ischemic stroke is possible, but the mechanisms involved in this process remain unclear. Researchers identified a whole new pathway promoting brain repair. They discovered lipids secreted from neurons surrounding the area of cell death can trigger brain-autonomous neural repair after ischemic brain injury. These findings might contribute to developing new compounds to stimulate the brain's intrinsic repair mechanisms. Patients often experience functional decline after an ischemic stroke, especially due to the brain's resistance to regenerate after damage. Yet, there is still potential for recovery as surviving neurons can activate repair mechanisms to limit and even reverse the damage caused by the stroke. How is it triggered though? In a study published recently in Neuron, researchers from Tokyo Medical and Dental University (TMDU) provided new insights regarding this question by identifying a new mechanism. They discovered that neurons surrounding the area of cell death secrete lipids that can trigger brain-autonomous neural repair after ischemic brain injury. An ischemic stroke occurs when the blood supply to the brain is blocked and results in the death of brain cells. This condition is life-threatening, and patients will likely develop functional disabilities. Although the adult brain can self-repair, the underlying mechanisms need further clarification. Inflammation of the brain contributes to the effects of ischemic stroke. "There is evidence that more lipids are produced after tissue injuries and contribute to regulating inflammation," says Takashi Shichita, senior author of the study. "We investigated the changes in lipid metabolite production in mice after ischemic stroke. Interestingly, the levels of a specific fatty acid called dihomo-γ-linolenic acid (DGLA) and its derivatives increased after the stroke." The researchers further discovered that a protein known as PLA2GE2 (Phospholipase A2 Group IIE, an enzyme) mediates DGLA increase. By manipulating the expression of PLA2GE2, they also showed its impact on functional recovery. Deficiency of PLA2GE2 led to more inflammation, lower expression of factors stimulating neuronal repair, and more tissue loss. The team carried on with identifying the targets of PLA2GE2/DGLA. "When we look at genes expressed in mice lacking PLA2GE2, we found low levels of a protein called peptidyl arginine deiminase 4 (PADI4)," explains Akari Nakamura, lead author of the study. "PADI4 regulates transcription and inflammation. Remarkably, expressing PADI4 in mice limited the extent of tissue damage and inflammation after ischemic stroke!" Additionally, the study shows that PADI4 promotes the transcription of genes involved in brain repair. It also identifies the whole signaling pathway involved in this process. Most data were obtained in a mouse model of ischemic stroke. Yet, the recovery pathway likely exists in humans as the researchers found that neurons surrounding the stroke site express PLA2G2E and PADI4 in humans. Moreover, another recent study reported that the lower serum DGLA level was correlated with the severe ischemic stroke and cognitive disorders in humans. This study describes a new mechanism that triggers brain repair after an ischemic stroke, which might lead to the development of compounds promoting PADI4's effects, that stimulate the recovery of patients. It could also change our current understanding and approach toward Eicosapentaenoic acid (EPA) or Docosahexaenoic acid (DHA), as the only beneficial lipids for preventing atherosclerosis and vascular diseases.

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.