Last update 06 Dec 2024
Milciclib maleate
Last update 06 Dec 2024
Overview
Basic Info
Drug Type Small molecule drug |
Synonyms Milciclib, PHA 848125C, PHA-125 + [5] |
Mechanism CDK1 inhibitors(Cyclin-dependent kinase 1 inhibitors), CDK2 inhibitors(Cyclin-dependent kinase 2 inhibitors), CDK4 inhibitors(Cyclin-dependent kinase 4 inhibitors) |
Therapeutic Areas |
Active Indication |
Inactive Indication |
Originator Organization |
Active Organization |
Inactive Organization |
Drug Highest PhasePhase 2 |
First Approval Date- |
RegulationOrphan Drug (US) |
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Structure
Molecular FormulaC29H36N8O5 |
InChIKeyDGVCEXQFNYYRQI-BTJKTKAUSA-N |
CAS Registry1253645-38-3 |
Related
9
Clinical Trials associated with Milciclib maleateMilciclib in Combination With Gemcitabine in Advanced Non-Small Cell Lung Cancer
The goal of this interventional clinical study is to evaluate the safety and efficacy of Milciclib plus gemcitabine in the treatment of persons with advanced NSCLC. This is an open label uncontrolled clinical trial
Eligible patients will receive 150 mg/day of milciclib orally using the 7 days on/7 days off schedule in combination with gemcitabine at the dose of 1000 mg/m² on Days 1, 8, and 15 every 4 weeks. Treatment cycles will be repeated every 4 weeks until progressive disease (radiologic or symptomatic deterioration), the start of a new systemic anticancer therapy, unacceptable toxicity, withdrawal per investigator's judgment, or withdrawal of consent, whichever occurs first.
Eligible patients will receive 150 mg/day of milciclib orally using the 7 days on/7 days off schedule in combination with gemcitabine at the dose of 1000 mg/m² on Days 1, 8, and 15 every 4 weeks. Treatment cycles will be repeated every 4 weeks until progressive disease (radiologic or symptomatic deterioration), the start of a new systemic anticancer therapy, unacceptable toxicity, withdrawal per investigator's judgment, or withdrawal of consent, whichever occurs first.
Start Date15 Mar 2023 |
Sponsor / Collaborator |
Phase IIA Exploratory Study of Oral Milciclib Maleate in Patients With Unresectable or Metastatic Hepatocellular Carcinoma
The primary aim of this exploratory study is to test the safety and tolerability of milciclib when administered orally at 100 mg in patients with recurrent or metastatic Hepatocellular Carcinoma. The evaluation of the efficacy profile is a secondary objective of the study. Moreover, markers expression in tumor cells and plasma will be studied and described in association with the clinical outcome.
Eligible patients will receive milciclib orally on a daily schedule for 4 consecutive days a week in a 4-week cycle (4 days on/3 days off x q4 wks) for a total of 12 weeks (i.e. 3 cycles) unless patient refusal, consent withdrawal, Investigator's decision, unacceptable toxicity or death whichever occurs earlier.
At the end of Cycle 3, treatment will be stopped, and based on the results of the tumor assessment performed on Day 90 (±3 days) from treatment start, patients will be followed as here below detailed:
patients with Complete Response (CR)/Partial Response (PR)/Stable Disease (SD) will be followed for safety until 30 days from last dose intake (or until a new anticancer therapy starts, whichever occurs earlier) and will be assessed for efficacy in the follow-up period up to Day 180 from treatment start;
patients with progressive disease will be followed only for safety until 30 days from last dose intake (or until a new anticancer therapy starts, whichever occurs earlier).
After the completion of three cycles, patients who, in the Investigator's judgment, are benefiting from treatment with milciclib, will resume treatment and will remain on study up to Day 180 from treatment start, unless withdrawal criteria are met earlier.
Eligible patients will receive milciclib orally on a daily schedule for 4 consecutive days a week in a 4-week cycle (4 days on/3 days off x q4 wks) for a total of 12 weeks (i.e. 3 cycles) unless patient refusal, consent withdrawal, Investigator's decision, unacceptable toxicity or death whichever occurs earlier.
At the end of Cycle 3, treatment will be stopped, and based on the results of the tumor assessment performed on Day 90 (±3 days) from treatment start, patients will be followed as here below detailed:
patients with Complete Response (CR)/Partial Response (PR)/Stable Disease (SD) will be followed for safety until 30 days from last dose intake (or until a new anticancer therapy starts, whichever occurs earlier) and will be assessed for efficacy in the follow-up period up to Day 180 from treatment start;
patients with progressive disease will be followed only for safety until 30 days from last dose intake (or until a new anticancer therapy starts, whichever occurs earlier).
After the completion of three cycles, patients who, in the Investigator's judgment, are benefiting from treatment with milciclib, will resume treatment and will remain on study up to Day 180 from treatment start, unless withdrawal criteria are met earlier.
Start Date12 Jul 2017 |
Sponsor / Collaborator |
Phase II study of oral PHA-848125AC in patients with malignant thymoma previously treated with multiple lines of chemotherapy
Start Date22 Apr 2013 |
Sponsor / Collaborator |
100 Clinical Results associated with Milciclib maleate
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100 Translational Medicine associated with Milciclib maleate
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100 Patents (Medical) associated with Milciclib maleate
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15
Literatures (Medical) associated with Milciclib maleate01 Nov 2023·Genomics
Comprehensive analysis of cuproptosis genes and cuproptosis-related genes as prognosis factors in esophageal squamous cell carcinoma
Article
Author: Huang, Zexin ; Wu, Bingli ; Wu, Zhisheng ; Zhou, Xiao ; Gao, Chenmeng ; Du, Zepeng ; Zhang, Yifan ; Zheng, Xiaoqi ; Peng, Zhongte
Esophageal squamous cell carcinoma (ESCC) is a common invasive and pernicious cancer with a low five-year survival rate. To identify potential therapeutic targets, we first investigated the characteristics of cuproptosis genes (CUGs) in ESCC. The expression patterns of 10 CUGs (FDX1, LIPT1, LIAS, DLAT, DLD, PDHA1, PDHB, GLS, MTF1, and CDKN2A) were analyzed to identify ESCC-relevant targets. Weighted correlation network analysis (WGCNA) was performed to obtain CUG-related genes (CRGs). A total of seven differentially expressed genes were identified (FDX1, DLAT, LIAS, PDHB, MTF1, GLS, and CDKN2A). DLAT was upregulated in stage III, and LIPT1 was upregulated in N0 + N1 cancers. The high expression of CDKN2A, and PDHA1, was related to better overall survival, whereas the low expression of LIAS was related to better clinical outcomes. WGCNA was performed to get CUG-related genes (CRGs) and showed three key modules that related to FDX1, DLAT, and LIPT1. Moreover, CRGs (BTLA, CT47A1, and PRRX1) were selected to construct a risk score model in order to predict the survival and prognosis of patients with ESCC. Additionally, the cuproptosis score based on CUGs and a nomogram constructed based on it helped accurately predict the prognosis of patients with ESCC; thus, maybe it can be used for the clinical diagnosis of ESCC. The results also showed that milciclib might inhibit the proliferation and migration of KYSE150 and KYSE510 cells by targeting CDKN2A. In conclusion, the abovementioned CUGs and CRGs play a crucial role in tumorigenesis and cancer progression in ESCC, indicating their potential as therapeutic targets.
01 Apr 2021·European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical SciencesQ2 · MEDICINE
The role of drug efflux and uptake transporters ABCB1 (P-gp), ABCG2 (BCRP) and OATP1A/1B and of CYP3A4 in the pharmacokinetics of the CDK inhibitor milciclib
Q2 · MEDICINE
Article
Author: Beijnen, Jos H ; Broeders, Jelle ; Martínez-Chávez, Alejandra ; Rosing, Hilde ; Lebre, Maria C ; Schinkel, Alfred H ; Tibben, Matthijs T
The promising anticancer drug milciclib potently inhibits cyclin-dependent kinase (CDK) 2 and tropomyosin receptor kinase (TRK) A, and is currently in phase II clinical studies. To characterize factors affecting milciclib pharmacokinetics, we investigated whether milciclib is a substrate of the multidrug efflux and uptake transporters ABCB1 (P-gp), ABCG2 (BCRP), and OATP1A/1B, and the drug-metabolizing enzyme CYP3A, using genetically-modified mouse models and Madin-Darby Canine Kidney (MDCK-II) cells. In vitro, milciclib was transported by mAbcg2, and this was inhibited by the ABCG2 inhibitor Ko143. Upon oral administration of milciclib, its plasma exposure in Abcb1a/1b-/-, Abcg2-/-, and Abcb1a/1b;Abcg2-/- mice was similar to that found in wild-type mice. Milciclib showed good brain penetration even in wild-type mice (brain-to-plasma ratio of 1.2), but this was further increased by 5.2-fold when both Abcb1 and Abcg2 were ablated, and to a lesser extent in single Abcb1- or Abcg2-deficient mice. Oatp1a/1b deficiency had only a minor impact on the milciclib plasma AUC0-24h and Cmax. The milciclib AUC0-8h increased 1.9-fold in Cyp3a-/- mice but decreased only 1.3-fold upon overexpression of human CYP3A4. Thus, ABCB1 and ABCG2 cooperatively limit milciclib brain penetration. The low impact of OATP1 and CYP3A could be clinically favorable for milciclib, reducing the risks of unintended drug-drug interactions or interindividual variation in CYP3A4 activity.
01 Oct 2020·Journal of pharmaceutical and biomedical analysisQ3 · MEDICINE
Development and validation of an LC-MS/MS method for the quantitative analysis of milciclib in human and mouse plasma, mouse tissue homogenates and tissue culture medium
Q3 · MEDICINE
Article
Author: Beijnen, Jos H ; Broeders, Jelle ; Martínez-Chávez, Alejandra ; Rosing, Hilde ; Schinkel, Alfred H ; Tibben, Matthijs M
Milciclib is a promising cyclin-dependent kinase inhibitor currently in phase II clinical trials to treat several types of cancer. The first bioanalytical method for the quantitative analysis of milciclib in several biomatrices using liquid chromatography-tandem mass spectrometry is described here. This method was fully validated in human plasma according to FDA and EMA guidelines, and partially validated in mouse plasma, homogenates of mouse brain, kidney, liver, small intestine, spleen, and tissue culture medium. Palbociclib, an analog compound, was used as internal standard. A simple and fast sample pre-treatment by protein precipitation with acetonitrile was used, leading to efficient extraction of the analyte with recoveries between 95-100%. Chromatographic separation was achieved with a C18 analytical column and a gradient elution using 10 mM ammonium bicarbonate in water and 10 mM ammonium bicarbonate in water-methanol (1:9, v/v). This assay was selective, accurate, precise and linear in the concentration range of 1-1000 ng/mL. Moreover, samples above the upper limit of quantification can be integrally diluted up to 10-fold prior to analysis. The use of human plasma as a surrogate matrix to quantify milciclib in tissue culture medium and mouse matrices resulted in acceptable accuracy and precision, however tissue culture medium samples required a dilution with human plasma prior the pre-treatment. All performance parameters of the method complied with the acceptance criteria recommended by the guidelines, except for the carry-over, which was slightly above (22.9% of the lower limit of quantification) the recommended percentage (20%). Therefore, additional measures were taken to assure data integrity. Stability of milciclib in all matrices was evaluated, and in some matrices the analyte was unstable under the tested conditions. It is therefore recommended to keep these samples as briefly as possible at room temperature during the pre-treatment, and to store them at -70 °C to avoid analyte degradation. This method was successfully applied to support preclinical pharmacokinetic studies of milciclib.
50
News (Medical) associated with Milciclib maleate26 Apr 2023
NEW YORK, April 26, 2023 (GLOBE NEWSWIRE) -- Tiziana Life Sciences, Ltd. (Nasdaq: TLSA) (“Tiziana” or the “Company”), a biotechnology company developing breakthrough immunomodulation therapies via novel routes of drug delivery, today announced financial results for the twelve months ended December 31, 2022, and provided a corporate update on its lead programs in development. Gabriele Cerrone, Executive Chairman, founder and interim Chief Executive Officer of Tiziana, commented, “After announcing our focus on advancing intranasal foralumab to address CNS-mediated inflammatory diseases, we have started this year with a stream of continuous, positive program-related developments. Intranasal foralumab’s unique action on regulatory T-cells and its potential to treat multiple inflammatory pathology indications has been published in a major medical journal and recognized in the media. We also recently announced intranasal foralumab’s potential to treat Long Covid, Alzheimer’s and Type 1 diabetes. Our near-term strategic focus is to prioritize resources for the clinical development of this unique therapeutic candidate to maximize shareholder value while still maintaining optionality for our other research programs, including milciclib in oncology. We aim to become a leading company pioneering intranasal therapies for inflammatory diseases”. Fourth Quarter 2022 Developments Related to Foralumab In October: Tiziana announced that it plans to submit an Investigational New Drug Application (IND) for a Phase 1 Trial of intranasal foralumab in Alzheimer's disease patients after receiving an affirmative written response from the FDA on a Pre-Investigational New Drug Application (PIND). Tiziana plans on filing the IND for Alzheimer’s disease by the second quarter of 2023 upon the completion of requested toxicology studies. In November: Tiziana announced publication of a scientific article in the peer-reviewed journal Frontiers in Immunology entitled “Nasal administration of anti-CD3 monoclonal antibody modulates effector CD8+ T cell function and induces a regulatory response in T cells in human subjects” (1). The study was completed by researchers at the Brigham and Women’s Hospital (BWH) and Harvard Medical School. The goal of the study was to assess safety and the immune effects of an entirely human, previously uncharacterized nasal anti-CD3 mAb (foralumab) in humans and it’s in vitro stimulatory properties. The findings support Tiziana’s intranasal foralumab platform as a new modality for the treatment of autoimmune and CNS diseases.Tiziana announced a corporate update, including its near-term focus on developing intranasal foralumab for inflammatory diseases of the Central Nervous System (CNS) such as non-active secondary-progressive Multiple Sclerosis (SPMS), Alzheimer’s disease and amyotrophic lateral sclerosis (ALS). Tiziana announced completion of enrollment of the first patient cohort (n=4) in its Intermediate-Size Patient Population Expanded Access Program to evaluate foralumab in non-active Secondary Progressive Multiple Sclerosis (SPMS). In December: Tiziana announced completion of the in-life portion of a 13-week, Good Laboratory Practice (GLP) foralumab intranasal pre-clinical study in transgenic HuGEMM CD3 mouse models. The study showed that intranasal foralumab, administered to the transgenic mice at doses up to 50 µg/rodent, was clinically well tolerated. 2023 Recent Clinical Program Updates In January: Tiziana announced that the second patient in its Expanded Access trial (“EA2”) with non-active secondary progressive multiple sclerosis (SPMS) receiving intranasal foralumab showed additional clinical improvements since his last reported improvement in September 2022. The improvements were measured by the Expanded Disability Status Scale (EDSS), a U.S. Food and Drug Administration (FDA) - recognized standard clinical outcome assessment. In March: Tiziana announced a publication in the preeminent1 journal, Proceedings of the National Academy of Sciences (PNAS), that illustrates the immunological basis of the mechanism of action (MoA) for intranasal foralumab. The publication highlights that the immunological basis of the mechanism of action for intranasal foralumab is based on increasing production of naïve-like T cells and Tregs, while simultaneously decreasing the production of effector T cells. Further, the publication demonstrates that intranasal foralumab has similar immune gene expression effects in COVID patients, MS patients and in heathy volunteers. The study concludes that immunomodulation by nasal anti-CD3 mAb represents a novel avenue for treatment of inflammatory human diseases. A copy of the publication can be found at pnas.org.2 As a result of this publication, Dr. Tanuja Chitnis, M.D., Professor of Neurology at Brigham Women’s Hospital, a founding member of Mass General Brigham Healthcare System, and lead investigator of the study, noted that foralumab also “makes a promising therapeutic candidate for several rare Orphan pediatric neuroinflammatory diseases, which currently remain untreated.” Tiziana announced its intention to start a Phase 2 study in the third quarter of 2023 in patients with non-active Secondary Progressive Multiple Sclerosis (SPMS) employing intranasal foralumab.Tiziana announced data from a pre-clinical study on the effects of intranasal foralumab in Alzheimer's disease which were presented on April 1, 2023, at the International Conference on Alzheimer's and Parkinson’s Disease and Related Neurological Disorders by Dr. Howard Weiner, M.D., Co-Director of the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital. The data showed reduction of microglia activation and improvement in behavior in animal models of Alzheimer’s disease.Additionally, Tiziana’s foralumab was highlighted in a Forbes magazine article entitled "New T Cell Antibody Treatment Improves Outcomes for Covid Patients" authored by contributing author, thought leader and pioneer in genomic sciences, William A. Haseltine who stated “Foralumab induces many factors that impact improved tissue remodeling, induction of immune cells, and restriction of effector function, improving disease outcomes while fighting the virus to full strength. These benefits are not limited to Covid-19 patients, as similar results were observed in patients with multiple sclerosis.” In April: Tiziana announced data from a pre-clinical study on the effects of intranasal foralumab in intracerebral hemorrhage (hemorrhagic stroke) that demonstrated one-month behavioral outcomes improvement and modulation of neuroinflammation. These data were presented in a podium presentation by Dr. Saef Izzy, M.D., MBCHB, Assistant Professor of Neurology at Harvard Medical School on April 23, 2023, at the American Academy of Neurology (AAN) annual meeting.Tiziana plans to investigate intranasal foralumab for the treatment of Long COVID. The work is supported by foralumab’s well-established role in de-activating microglia cells, a key component in the pathogenesis of this disease. The Company anticipates entering into a Phase 2a, placebo-controlled, clinical trial upon successful feedback from the FDA.Tiziana Life Sciences to file Alzheimer’s IND for intranasal foralumab in the second quarter of 2023. Additionally, an application for $3M of non-dilutive funding to support a Phase 2a Alzheimer’s trial will be submitted in the second quarter of 2023 with a response expected in the third quarter of 2023.Tiziana also announced that it is initiating a program to develop intranasal foralumab for the treatment or delay of Type 1 Diabetes. 2022 Year End Financial Results For the twelve months ended 31 December 2022 Tiziana reported a loss of $19.0 million compared to $27.9 million in the twelve months ended 31 December 2021.Research and development (R&D) expenses decreased to $13.0 million compared to $13.2 million in the twelve months ended 31 December 2021. The decrease is primarily related to the focus on the Company’s proprietary programs, foralumab and to a lower extent, IL6-R.Tiziana ended the period with $18.1 million cash as of 31 December 2022 as compared to $42.2 million on 31 December 2021.Tiziana’s Annual Report on Form 20-F can be accessed by visiting either the SEC’s website at www.sec.gov or the Investors section of the Company’s website at ir.tizianalifesciences.com/financial-information/annual-reports. [1] https://www.pnas.org/about/article-journal-metrics [2] https://www.pnas.org/doi/10.1073/pnas.2220272120 About ForalumabActivated T cells play an important role in the inflammatory process. Foralumab, the only fully human anti-CD3 monoclonal antibody (mAb), binds to the T cell receptor and dampens inflammation by modulating T cell function, thereby suppressing effector features in multiple immune cell subsets. This effect has been demonstrated in patients with COVID and with multiple sclerosis, as well as in healthy normal subjects. Intranasal foralumab Phase 2 trials are expected to start in the third quarter of 2023 in patients with non-active SPMS. Immunomodulation by nasal anti-CD3 mAb represents a novel avenue for treatment of inflammatory human diseases.[1] About Tiziana Life SciencesTiziana Life Sciences is a clinical-stage biopharmaceutical company developing breakthrough therapies using transformational drug delivery technologies to enable alternative routes of immunotherapy. Tiziana’s innovative nasal approach has the potential to provide an improvement in efficacy as well as safety and tolerability compared to intravenous (IV) delivery. Tiziana’s lead candidate, intranasal foralumab, which is the only fully human anti-CD3 mAb, has demonstrated a favorable safety profile and clinical response in patients in studies to date. Tiziana’s technology for alternative routes of immunotherapy has been patented with several applications pending and is expected to allow for broad pipeline applications. For further inquiries: Tiziana Life Sciences LtdPaul Spencer, Business Development and Investor Relations+44 (0) 207 495 2379email: info@tizianalifesciences.com Investors:Irina KofflerLifeSci Advisors, LLC646.970.4681ikoffler@lifesciadvisors.com
Phase 2Immunotherapy
05 Jan 2023
NEW YORK, Jan. 04, 2023 (GLOBE NEWSWIRE) -- Tiziana Life Sciences Ltd. (Nasdaq: TLSA) (“Tiziana” or the “Company”), a biotechnology company developing breakthrough immunomodulation therapies via novel routes of drug delivery, today announced the Investigational New Drug (IND) application filing for milciclib in combination with gemcitabine for non-small cell lung cancer (NSCLC).
“This Phase 2 IND filing, which was achieved with minimal additional resource deployment, enhances the asset value and Tiziana’s optionality for milciclib," commented Gabriele Cerrone, Executive Chairman and interim Chief Executive Officer of Tiziana. “Milciclib previously showed encouraging results in several cancer clinical studies - both as a monotherapy and in combination with gemcitabine. We believe that there could be an important role for a pan-CDK inhibitor in the oncologist’s toolbox. At the same time, we are highly focused on advancing our leading CNS-focused programs with intranasal foralumab, which continues to generate encouraging data in our expanded access trial of secondary progressive multiple sclerosis.”
About Milciclib
Milciclib is a potent, small molecule inhibitor of multiple cyclin-dependent kinases (CDKs), tropomyosin receptor kinases and Src family kinases controlling cell growth and malignant progression of cancer. Milciclib has demonstrated safety in 316 patients with advanced solid cancers in Phase 1 and 2 studies and shown indications of efficacy. In two completed Phase 2 thymic cancer trials, milciclib successfully increased overall survival and met both primary and secondary endpoints.
About Tiziana Life Sciences
Tiziana Life Sciences is a clinical-stage biopharmaceutical company developing breakthrough therapies using transformational drug delivery technologies to enable alternative routes of immunotherapy. Tiziana’s innovative nasal, oral and inhalation approaches in development have the potential to provide an improvement in efficacy as well as safety and tolerability compared to intravenous (IV) delivery. Tiziana’s two lead candidates, intranasal foralumab, the only fully human anti-CD3 mAb, and milciclib, a pan-CDK inhibitor, have both demonstrated a favorable safety profile and clinical response in patients in studies to date. Tiziana’s technology for alternative routes of immunotherapy has been patented with several applications pending and is expected to allow for broad pipeline applications.
Phase 2ImmunotherapyINDClinical Result
04 Jan 2023
NEW YORK, Jan. 03, 2023 (GLOBE NEWSWIRE) -- Tiziana Life Sciences Ltd. (Nasdaq: TLSA) (“Tiziana” or the “Company”), a biotechnology company developing breakthrough immunomodulation therapies via novel routes of drug delivery, today announced that the second patient (“EA2”) with non-active secondary progressive multiple sclerosis (SPMS) receiving intranasal foralumab has shown additional clinical improvements since their last reported improvement in September 2022. The improvements were measured by the Expanded Disability Status Scale (EDSS), a U.S. Food and Drug Administration (FDA) - recognized standard clinical outcome assessment that is a measure of neural network functioning, rating different measures from 1 to 10 (disability increasing with higher scores).
Before foralumab treatment, EA2’s non-active SPMS disability had progressed and EDSS worsened from 3.5 in 2018 to 6.0 in 2021 despite ocrelizumab therapy. Ocrelizumab was discontinued in 2021. At this point, EA2 required a cane to walk 100 meters. EA2 was subsequently enrolled in the intranasal foralumab Expanded Access program in January 2022. In September 2022, 8 months after starting treatment with nasal foralumab, EA2 was able to walk 100 meters without a cane. EDSS score improved from 6.0 to 5.5. EA2’s pyramidal score remained stable during this time. In December 2022, 11 months after starting treatment with intranasal foralumab, EA2 was able to walk 200 meters without a cane, resulting in an even greater improvement in EDSS; with EDSS falling from a score of 5.5 to 5.0. EA2’s pyramidal score continued to remain stable.
Dr. Tanuja Chitnis, M.D., Professor of Neurology and the Principal investigator of the clinical study at BWH said, “The sustained improvement in EDSS score starting at 6 months and further improving after 11 months on foralumab treatment in patient EA2 is impressive and warrants further study in a Phase 2 trial. Patients with non-active SPMS normally do not improve by a sustained reduction of 1.0 on their EDSS score, so this finding is noteworthy.”
Howard L. Weiner, M.D., Co-Director of the Ann Romney Center for Neurologic Diseases at BWH and Chairman of Tiziana's Scientific Advisory Board, stated, “SPMS represents an advanced stage of multiple sclerosis with few treatment options and creates a severe burden on patients. It is gratifying to see a 1.0 EDSS improvement in patient EA2 following treatment with intranasal foralumab.”
“Six patients are currently enrolled and are being followed in our intranasal foralumab program. EA2’s clinical improvement justifies Tiziana’s decision to make intranasal foralumab for non-active SPMS our top priority,” commented Gabriele Cerrone, Executive Chairman and interim Chief Executive Officer of Tiziana.
About Foralumab
Foralumab (formerly NI-0401), the only entirely human anti-CD3 mAb, has shown reduced release of cytokines after IV administration in healthy volunteers and in patients with Crohn's disease. In a humanized mouse model (NOD/SCID IL2γc-/-), it was shown that while targeting the T-cell receptor, orally administered foralumab modulates immune responses of the T-cells and enhances regulatory T-cells (Tregs), thereby providing therapeutic benefit in treating inflammatory and autoimmune diseases without the occurrence of potential adverse events usually associated with parenteral mAb therapy. Once a day treatment for 10 consecutive days with intranasal foralumab was both well tolerated and produced clinical responses in COVID-19 patients. Based on these studies, the intranasal and oral administration of foralumab offers the potential to become a well-tolerated immunotherapy for autoimmune and inflammatory diseases by the induction of Tregs.
About Tiziana Life Sciences
Tiziana Life Sciences is a clinical-stage biopharmaceutical company developing breakthrough therapies using transformational drug delivery technologies to enable alternative routes of immunotherapy. Tiziana’s innovative nasal, oral and inhalation approaches in development have the potential to provide an improvement in efficacy as well as safety and tolerability compared to intravenous (IV) delivery. Tiziana’s two lead candidates, intranasal foralumab, the only fully human anti-CD3 mAb, and milciclib, a pan-CDK inhibitor, have both demonstrated a favorable safety profile and clinical response in patients in studies to date. Tiziana’s technology for alternative routes of immunotherapy has been patented with several applications pending and is expected to allow for broad pipeline applications.
ImmunotherapyPhase 2Clinical Result
100 Deals associated with Milciclib maleate
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R&D Status
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| Indication | Highest Phase | Country/Location | Organization | Date |
|---|---|---|---|---|
| Advanced Lung Non-Small Cell Carcinoma | Phase 2 | - | 15 Mar 2023 | |
| Metastatic hepatocellular carcinoma | Phase 2 | GR | 12 Jul 2017 | |
| Metastatic hepatocellular carcinoma | Phase 2 | IL | 12 Jul 2017 | |
| Metastatic hepatocellular carcinoma | Phase 2 | IT | 12 Jul 2017 | |
| Unresectable Hepatocellular Carcinoma | Phase 2 | GR | 12 Jul 2017 | |
| Unresectable Hepatocellular Carcinoma | Phase 2 | IL | 12 Jul 2017 | |
| Unresectable Hepatocellular Carcinoma | Phase 2 | IT | 12 Jul 2017 | |
| Thymoma | Phase 2 | US | 02 Feb 2011 | |
| Thymoma | Phase 2 | IT | 02 Feb 2011 | |
| thymic carcinoma | Phase 2 | US | 22 Feb 2010 |
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Clinical Result
Clinical Result
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Phase
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| Study | Phase | Population | Analyzed Enrollment | Group | Results | Evaluation | Publication Date |
|---|
NCT03109886 (ASCO2020) Manual  | Phase 2 | 31 | wausfdkesb(bvketnsofu) = 25.8% with most frequent (≥5%) occurrence of drug-related diarrhea, nausea, asthenia, fatigue, retinal hemorrhage, rash and myalgia iqbhipnlfz (klermeohdg ) View more | Positive | 29 May 2020 | ||
Phase 2 | 72 | skqsltydsh(abzqatpojb) = usvfdmcufr memplqgknw (brkuczxptp, gjhxfrujfy - oeeehrlasc) View more | - | 16 Oct 2018 | |||
Phase 2 | 30 | kovrqqbtcy(alscdvwdfy) = ntbwgnwuvf pgydrshehu (bzwddvtrjh, nejynrzqvl - rdziueqjxf) View more | - | 04 Oct 2018 | |||
Phase 2 | 102 | (CDKO-125A-006：previously treated with one chemotherap) | djkhufjbcw(dahpbtjqwu) = unmhuxnroc mayetniqjf (cjhiahlldk ) View more | Positive | 03 Jun 2018 | ||
(CDKO-125A-007：previously treated with multiple chemotherapies) | djkhufjbcw(dahpbtjqwu) = psibsgvtsx mayetniqjf (cjhiahlldk ) View more | ||||||
Phase 2 | 54 | bbkviluzpt(mycczgjlss) = 5.6% lymmqldmtj (mkgifohxys ) View more | - | 20 May 2014 | |||
Phase 1 | - | ljamgiqpvb(ygkhzaaqrp) = fmmijuyezp esybqstiov (qnvptlgnwz ) | - | 20 May 2010 | |||
Phase 1 | - | yiqbhobdgz(bprlweykkf) = rlhxjolugn pfdljtlovb (tcmwkhqkqd ) View more | - | 20 May 2010 |
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