PDL1 inhibitors(Programmed death-ligand 1 inhibitors), PDL2 inhibitors(Programmed cell death 1 ligand 2 inhibitors), VISTA inhibitors(V-domain Ig suppressor of T-cell activation inhibitors)

Therapeutic Areas

Neoplasms

Active Indication

Neoplasms

Inactive Indication

Advanced Malignant Solid NeoplasmBladder CancerColorectal Cancer+ [10]

Originator Organization

Aurigene Oncology Ltd.

Active Organization

Aurigene Oncology Ltd.

Curis, Inc.

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

Clinical Trials associated with CA-170

CTRI/2020/07/026870 / RecruitingPhase 2/3

A Phase IIb/III, Randomised, Double-blind, Placebo-controlled, Multicentre,Study of CA-170 in Combination with Chemotherapy and Radiation in Patients with Unresectable Stage III or IVa Non-Squamous Non-Small Cell Lung Cancer (ASIAD-2) - ASIAD-2

Start Date03 Aug 2020

Sponsor / Collaborator-

CTRI/2017/12/011026 / TerminatedPhase 2

A Phase 2, Open-Label Randomized Trial Evaluating the Efficacy and Safetyof Two Dosages of Once Daily Oral CA-170 in Patients with Selected RelapsedAdvanced Tumors (ASIAD)

Start Date12 Jan 2018

Sponsor / Collaborator

Aurigene Oncology Ltd.

NCT02812875 / CompletedPhase 1

A Phase 1, Open-Label, Dose Escalation and Dose Expansion Trial Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Effects of Orally Administered CA-170 in Patients With Advanced Tumors and Lymphomas

CA-170 is a rationally designed and orally available, small molecule that directly targets the Programmed death-ligands 1 and 2 (PD-L1/PD-L2), and V-domain Ig suppressor of T cell activation (VISTA) immune checkpoints and results in activation of T cell proliferation and cytokine production. This is a multi-center, open-label, Phase 1 trial of orally administered CA-170 in adult patients with advanced solid tumors or lymphomas who have progressed or are non-responsive to available therapies and for which no standard therapy exists.

Start Date01 May 2016

Sponsor / Collaborator

Curis, Inc.

100 Clinical Results associated with CA-170

100 Translational Medicine associated with CA-170

100 Patents (Medical) associated with CA-170

Literatures (Medical) associated with CA-170

01 Jan 2024·Bioinformatics and Biology Insights

Unlocking Benzosampangine’s Potential: A Computational Approach to Investigating, Its Role as a PD-L1 Inhibitor in Tumor Immune Evasion via Molecular Docking, Dynamic Simulation, and ADMET Profiling

Article

Author: Ramli, Youssef ; Fadoua, Elkamili ; Hadad, Salah Eddine El ; Kettani, Anass ; Aherkou, Marouane ; Ouchaoui, Abderrahim Ait ; Mouad, Mkamel ; Bourais, Ilhame

The interaction between programmed cell death protein 1 (PD-1) and its ligand PD-L1 plays a crucial role in tumor immune evasion, presenting a critical target for cancer immunotherapy. Despite being effective, current monoclonal antibodies present some drawbacks such as high costs, toxicity, and resistance development. Therefore, the development of small-molecule inhibitors is necessary, especially those derived from natural sources. In this study, benzosampangine is predicted as a promising PD-L1 inhibitor, with potential applications in cancer immunotherapy. Utilizing the high-resolution crystal structure of human PD-L1 (PDB ID: 5O45), we screened 511 natural compounds, identifying benzosampangine as a top candidate with exceptional inhibitory properties. Molecular docking predicted that benzosampangine exhibits a strong binding affinity for PD-L1 (−9.4 kcal/mol) compared with established controls such as CA-170 (−6.5 kcal/mol), BMS-202 (−8.6 kcal/mol), and pyrvinium (−8.9 kcal/mol). The compound’s predicted binding efficacy is highlighted by robust interactions with key amino acids (ILE54, TYR56, GLN66, MET115, ILE116, SER117, ALA121, ASP122) within the active site, notably forming 3 Pi-sulfur interactions with MET115—an interaction absents in control inhibitors. In addition, ADMET profiling suggests that over the control molecules, benzosampangine has several key advantages, including favorable solubility, permeability, metabolic stability, and low toxicity, while adhering to Lipinski’s rule of five. Molecular dynamic simulations predict the stability of the benzosampangine-PD-L1 complex, reinforcing its potential to sustain inhibition of the PD-1/PD-L1 pathway. MMGBSA analysis calculated a binding free energy (ΔGbind) of −39.39 kcal/mol for the benzosampangine-PD-L1 complex, with significant contributions from Coulombic, lipophilic, and Van der Waals interactions, validating the predicted docking results. This study investigates in silico benzosampangine, predicting its better molecular interactions and pharmacokinetic profile compared with several already known PD-L1 inhibitors.

01 Dec 2021·BMC immunologyQ4 · MEDICINE

Identification of active small-molecule modulators targeting the novel immune checkpoint VISTA

Q4 · MEDICINE

ArticleOA

Author: Liu, Jun ; Jiang, Jing-Wei ; Chen, Wen-Ting ; Xuan, Chun-Xiao ; Hu, Xin-Lei ; Liu, Wan-Mei ; Li, Ting-Ting ; Qie, Chen-Xin

Abstract:

Background:

Cancer immunotherapy has gained increasing popularity as a novel approach to treat cancer. A member of the B7 family, V-domain immunoglobulin suppressor of T-cell activation (VISTA) is a novel immune checkpoint that regulates a broad spectrum of immune responses. VISTA is an acidic pH-selective ligand for P-selectin glycoprotein ligand-1(PSGL-1). CA-170, a first-in-class small-molecule dual antagonist of VISTA/PD-L1, was collaboratively developed by Aurigene Discovery Technologies Limited and Curis, Inc. It is currently in Phase I clinical trial.

Results:

In this study, we develop homology modeling for the VISTA 3D structure and subsequent virtual screening for VISTA small-molecule hit ligands. Visualization of the binding postures of docked ligands with the VISTA protein indicates that some small molecular compounds target VISTA. The ability of antagonist to disrupt immune checkpoint VISTA pathways was investigated though functional studies in vitro.

Conclusions:

Affinity active molecule for VISTA was obtained through virtual screening, and the antagonist compound activity to VISTA was assayed in cellular level. We reported a small molecule with high VISTA affinity as antagonist, providing ideas for development VISTA-targeted small molecule compound in cancer immunotherapy.

01 Jan 2019·ESMO openQ3 · MEDICINE

New emerging targets in cancer immunotherapy: the role of VISTA

Q3 · MEDICINE

ReviewOA

Author: Novello, Silvia ; Bironzo, Paolo ; Tagliamento, Marco

The immune surveillance system is complex and regulated by different actors. Programmed death protein-ligand 1 (PD-L1), the only approved biomarker in clinical practice, has proven to be imperfect in selecting patients to immune checkpoint inhibitors treatment. Therefore, new biomarkers, and new therapeutic targets, are needed to maximise the efficacy of immunotherapy. V-domain Ig Suppressor of T-cell Activation (VISTA) is a programmed death protein-1 (PD-1) homolog expressed on T cells and on antigen-presenting cells, which regulates processes of activation and repression of the immune system with not yet completely clarified mechanisms. Its blockage has demonstrated in vitro and in vivo antitumour activity. The clinical research of VISTA antagonists is ongoing. Particularly, CA-170, an orally delivered dual inhibitor of VISTA and PD-L1, has shown to have clinical efficacy in phase I and II clinical trials in different advanced solid tumour types. Further data are needed to define whether this drug class can become a new therapeutic option for patients with VISTA expressing cancers.

News (Medical) associated with CA-170

06 Oct 2023

·www.biospace.com

Curis Reports Inducement Grants Under NASDAQ Listing Rule 5635(c)(4) - October 06, 2023

LEXINGTON, Mass., Oct. 6, 2023 /PRNewswire/ -- Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, today announced that on October 2, 2023, the independent Compensation Committee of the Board of Directors of Curis approved the grant of inducement stock options to purchase a total of 11,340 shares of Curis common stock to two new employees, with a grant date of October 2, 2023 (the "Q4 2023 Inducement Grants"). Each of the Q4 2023 Inducement Grants has an exercise price per share equal to the closing price of the Company's common stock on October 2, 2023. Each stock option has a 10 year term and vests over four years, with 25% of the original number of shares underlying the award vesting on the first anniversary of the employee's date of hire and an additional 6.25% of the original number of shares underlying the award vesting on each successive three-month period thereafter, subject to the employee's continued service with the Company through the respective vesting dates. Each stock option was granted as an inducement equity award outside of the Company's Fourth Amended and Restated 2010 Stock Incentive Plan and was made as an inducement material to the employee's acceptance of employment with the Company. About Curis, Inc. Curis is a biotechnology company focused on the development of emavusertib, an orally available, small molecule IRAK4 inhibitor for the treatment of hematologic malignancies. In 2015, Curis entered into a collaboration with Aurigene in the areas of immuno-oncology and precision oncology. As part of this collaboration, Curis has exclusive licenses to oral small molecule antagonists of immune checkpoints including the VISTA/PDL1 antagonist CA-170, and the TIM3/PDL1 antagonist CA-327, as well as the IRAK4 kinase inhibitor, emavusertib (CA-4948). Emavusertib is currently undergoing testing in the Phase 1/2 TakeAim Lymphoma trial in patients with hematologic malignancies, such as non-Hodgkin's lymphoma and other B cell malignancies, both as a monotherapy and in combination with BTK inhibitor ibrutinib, and the Phase 1/2 TakeAim Leukemia trial in patients with acute myeloid leukemia and myelodysplastic syndrome, for which it has received Orphan Drug Designation from the U.S. Food and Drug Administration. In addition, Curis is engaged in a collaboration with ImmuNext for development of CI-8993, a monoclonal anti-VISTA antibody. Curis is also party to a collaboration with Genentech, a member of the Roche Group, under which Genentech and Roche are commercializing Erivedge® for the treatment of advanced basal cell carcinoma. For more information, visit Curis's website at . View original content to download multimedia: SOURCE Curis, Inc. Company Codes: NASDAQ-NMS:CRIS

ImmunotherapyOrphan DrugLicense out/in

12 Sep 2023

·www.prnewswire.com

Curis Announces Date for the 2nd Symposium on IRAK4 in Cancer

Symposium hosted by Guillermo Garcia-Manero, M.D. and Eric Winer, M.D. Academics and industry professionals will gather virtually on September 22, 2023 LEXINGTON, Mass., Sept. 12, 2023 /PRNewswire/ -- Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of emavusertib, an orally available, small molecule IRAK4 inhibitor for the treatment of hematologic malignancies, today announced the 2nd Symposium on IRAK4 in Cancer taking place virtually on September 22, 9:00am-1:00pm ET. Hosted by Dr. Guillermo Garcia-Manero and Dr. Eric Winer, this symposium will focus on IRAK4, a key protein in the innate immune response and an emerging target in the treatment of hematologic malignancies and solid tumors. Experts across academia and industry will discuss IRAK4's biological and immunological roles as well as the promising role of targeting IRAK4 in cancer therapeutics. "Following the success of last year's symposium on IRAK4 in cancer, Curis is pleased to continue its sponsorship of the Annual IRAK4 Symposium," said James Dentzer, President, and Chief Executive Officer of Curis. "As a leader in IRAK4 inhibition in oncology with emavusertib, we are honored to provide a forum for discussing the biology of the IRAK4 pathway and IRAK4 inhibition in the research and development of therapies to benefit patients living with cancer." Symposium hosts: Guillermo Garcia-Manero, M.D. - Symposium Co-Chair - Professor, Department of Leukemia; Chief, Section of Myelodysplastic Syndromes and Deputy Chair, Translational Research, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center Eric Winer, M.D. – Symposium Co-Chair – Clinical Director, Adult Leukemia Institute Physician, Dana-Farber Cancer Institute; Assistant Professor of Medicine, Harvard Medical School Joining our hosts will be the following speakers and participants: Omar Abdel-Wahab, M.D. - Edward P. Evans Chair in MDS, Director, Memorial Sloan Kettering Cancer Center (MSK) for Hematologic Malignancies; Member, Human Oncology and Pathogenesis Program & Leukemia Service Claudio Cerchione, M.D., Ph.D. - Hematologist, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS Bentley Doonan, M.D., M.S. - Assistant Professor, Division of Hematology & Oncology, University of Florida College of Medicine Matthew Galsky, M.D. - Professor of Medicine (Hematology and Medical Oncology), Director of Genitourinary Medical Oncology, Co-Director of the Center of Excellence for Bladder Cancer, Associate Director for Translational Research, Tisch Cancer institute Christian Grommes, M.D. – Associate Professor of Neurology, Weill Cornell Medical College; Assistant Professor of Neuroscience, Brain and Mind Research Institute, Weill Cornell Medical College; Neuro-oncologist, Memorial Sloan-Kettering Cancer Center Kian-Huat Lim, M.D., Ph.D. - Associate Professor, Division of Oncology, Department of Medicine, Washington University School of Medicine in St. Louis Daniel Starczynowski, Ph.D. – Institute Associate Director for Basic Science Research, University of Cincinnati Cancer Center; Co-Chief Scientific Officer, Innovations Ventures; Katherine Stewart Waters Endowed Chair of Hematologic Malignancies, Professor in Pediatrics, Co-Leader, Hematologic Malignancies Program, Cincinnati Children's Hospital Richard Stone, M.D. – Chief of Staff, Dana-Farber Cancer Institute; Director of Translational Research, Adult Acute Leukemia Program, Dana-Farber Cancer Institute; Professor of Medicine, Harvard Medical School Amit Verma, M.B.B.S. – Professor, Department of Oncology (Medical Oncology), Department of Medicine (Oncology & Hematology), and Department of Developmental & Molecular Biology, Albert Einstein College of Medicine; Director, Division of Hemato-Oncology, Montefiore Department of Oncology; Associate Director, Translational Science, Montefiore Einstein Cancer Center; Co-Director, Montefiore Einstein Blood Cancer Institute The virtual event will address topics including the biology of the IRAK4 pathway and the potential of IRAK4 inhibition in both hematologic malignancies and solid tumors. Presentations and a panel discussion will address IRAK4 biology and clinical experience with IRAK4 inhibition, the potential to overcome treatment resistance, biomarkers, and next steps in the field. To learn more about this free-to-attend symposium and register, please visit About Curis, Inc. Curis is a biotechnology company focused on the development of emavusertib, an orally available, small molecule IRAK4 inhibitor for the treatment of hematologic malignancies. In 2015, Curis entered into a collaboration with Aurigene in the areas of immuno-oncology and precision oncology. As part of this collaboration, Curis has exclusive licenses to oral small molecule antagonists of immune checkpoints including the VISTA/PDL1 antagonist CA-170, and the TIM3/PDL1 antagonist CA-327, as well as the IRAK4 kinase inhibitor, emavusertib (CA-4948). Emavusertib is currently undergoing testing in the Phase 1/2 TakeAim Lymphoma study in patients with hematologic malignancies, such as non-Hodgkin's lymphoma and other B cell malignancies, both as a monotherapy and in combination with the BTK inhibitor ibrutinib, and the Phase 1/2 TakeAim Leukemia study in patients with acute myeloid leukemia and myelodysplastic syndrome, for which it has received Orphan Drug Designation from the U.S. Food and Drug Administration. In addition, Curis is engaged in a collaboration with ImmuNext for development of CI-8993, a monoclonal anti-VISTA antibody. Curis is also party to a collaboration with Genentech, a member of the Roche Group, under which Genentech and Roche are commercializing Erivedge® for the treatment of advanced basal cell carcinoma. For more information, visit Curis' website at . SOURCE Curis, Inc.

Orphan DrugLicense out/in

06 Sep 2023

·www.biospace.com

Curis to Present at Upcoming Healthcare Conferences in September

LEXINGTON, Mass., Sept. 6, 2023 /PRNewswire/ -- Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of emavusertib, an orally available small molecule IRAK4 inhibitor for the treatment of hematologic malignancies, today announced that James Dentzer, President and Chief Executive Officer of Curis, will participate at the following conferences: The H.C. Wainwright 25th Annual Global Investment Conference being held September 11 – 13, 2023. Presentation details are as follows: Format: Company Presentation Date: Tuesday, September 12, 2023 Time: 8:30am ET The 2023 Cantor Global Healthcare Conference being held September 26 – 28, 2023. Presentation details are as follows: Format: Panel Presentation Date: Wednesday, September 27, 2023 Time: 9:10am ET Webcasts will be available on the Curis website at in the 'Investors' section. About Curis, Inc. Curis is a biotechnology company focused on the development of emavusertib, an orally available, small molecule IRAK4 inhibitor for the treatment of hematologic malignancies. In 2015, Curis entered into a collaboration with Aurigene in the areas of immuno-oncology and precision oncology. As part of this collaboration, Curis has exclusive licenses to oral small molecule antagonists of immune checkpoints including the VISTA/PDL1 antagonist CA-170, and the TIM3/PDL1 antagonist CA-327, as well as the IRAK4 kinase inhibitor, emavusertib (CA-4948). Emavusertib is currently undergoing testing in the Phase 1/2 TakeAim Lymphoma study in patients with hematologic malignancies, such as non-Hodgkin's lymphoma and other B cell malignancies, both as a monotherapy and in combination with BTK inhibitor ibrutinib, and the Phase 1/2 TakeAim Leukemia study in patients with acute myeloid leukemia and myelodysplastic syndrome, for which it has received Orphan Drug Designation from the U.S. Food and Drug Administration. In addition, Curis is engaged in a collaboration with ImmuNext for development of CI-8993, a monoclonal anti-VISTA antibody. Curis is also party to a collaboration with Genentech, a member of the Roche Group, under which Genentech and Roche are commercializing Erivedge® for the treatment of advanced basal cell carcinoma. For more information, visit Curis's website at . Company Codes: NASDAQ-NMS:CRIS

Orphan DrugLicense out/inImmunotherapy

100 Deals associated with CA-170

External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15772

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Non-Small Cell Lung Cancer	Phase 3	IN	-	05 Oct 2020
Lymphoma	Phase 2	IN	-	17 Feb 2018
Neoplasms	Phase 2	-	Curis, Inc.	-
Neoplasms	Phase 2	-	Aurigene Oncology Ltd.	-
Mesothelioma	Phase 1	US	Curis, Inc.	24 Jan 2019
Mesothelioma	Phase 1	KR	Curis, Inc.	24 Jan 2019
Mesothelioma	Phase 1	ES	Curis, Inc.	24 Jan 2019
Mesothelioma	Phase 1	GB	Curis, Inc.	24 Jan 2019
Advanced Malignant Solid Neoplasm	Phase 1	US	Curis, Inc.	01 May 2016
Advanced Malignant Solid Neoplasm	Phase 1	KR	Curis, Inc.	01 May 2016

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02812875 (CA-170-101, SITC2019) Manual	Phase 1	Malignant Pleural Mesothelioma	12	CA 170	medrfpifpg(rznngjphmx) = mkeewgffda gzrdaklwuk (ykkkijirbo ) View more	Positive	10 Nov 2019
NCT02812875 (ESMO2019)	Phase 2	Squamous non-small cell lung cancer Third line	62	400mg CA-170	xmhhmpprxs(apleljoqtl) = hgkznjqreg fqphrrkjhi (mzswfgvsvy ) View more	-	30 Sep 2019
NCT02812875 (ESMO2019)	Phase 2	Squamous non-small cell lung cancer Third line	62	800mg CA-170	xmhhmpprxs(apleljoqtl) = wvhdgejwdk fqphrrkjhi (mzswfgvsvy ) View more	-	30 Sep 2019
NCT02812875 (P714, SITC2018)	Phase 2	Hodgkin's Lymphoma \| Advanced Malignant Solid Neoplasm	58	CA-170 400mg	jxpllhgrop(vsvnzihyjm) = two patients developed skin rash, one patient developed hypothyroidism, and one patient developed Grade 3 neutropenia and anemia. Both anemia and neutropenia resolved upon drug interruption, however, neutropenia re-appeared after re-exposure, confirming causality. CA-170 was permanently discontinued without any sequalae, suggesting that smaller half life (6-8 hours) of CA-170 provides an advantage over longer lasting antibodies, from safety perspective. cqsloiahyz (mnicafxsqb )	Positive	01 Dec 2018
NCT02812875 (P139, SITC2018)	Phase 1	Hodgkin's Lymphoma \| Solid tumor \| Advanced Malignant Solid Neoplasm ... View more	41	CA-170 50 mg QD	vbvzzltyam(mwlpassifr) = pwgcshntkr vfxtwgevwm (ptafnuzmuv, 1.5 - 5) View more	Positive	06 Nov 2018
NCT02812875 (P139, SITC2018)	Phase 1		41	CA-170 100 mg QD	vbvzzltyam(mwlpassifr) = jexspuzbjc vfxtwgevwm (ptafnuzmuv, 1.5 - 5) View more	Positive	06 Nov 2018

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