onvatilimab (CI-8993) / ImmuNext, Curis - LARVOL DELTA

The bispecific antibody targeting VISTA and PD-L1 shows enhanced tumor inhibitory activity in pancreatic, endometrial and breast cancers compared to mono- and combination immune checkpoint blockade. (PubMed, Front Immunol) - "The bsAbs generated in this study showed weaker binding properties to PD-1 and VISTA in ELISA (EC50) than the parent antibodies (atezolizumab and onvatilimab). Both the asymmetric and symmetric bsAbs resulted in higher secretion levels of IFN-γ, TNFα and Granzyme B than anti-VISTA, anti-PD-L1 monotherapy and anti-VISTA/anti-PD-L1 combination therapy. The high level of tumor cell lysis and increased expression of pro-inflammatory cytokines induced by the Fc-based bsAbs suggest a novel approach for the treatment of pancreatic, endometrial and breast cancer."

Checkpoint inhibition • IO biomarker • Journal • Breast Cancer • Endometrial Cancer • Oncology • Pancreatic Cancer • Solid Tumor • GZMB • IFNG • TNFA

METTL3-VISTA axis-based combination immunotherapy for APC truncation colorectal cancer. (PubMed, J Immunother Cancer) - "We elucidate that an underappreciated function of truncated APC in CRC is its ability to drive an immunosuppressive program that boosts tumor progression. Our work could provide a new perspective for the clinical application of immunotherapy in patients with CRC resistant to ICB therapy."

IO biomarker • Journal • Colorectal Cancer • Oncology • Solid Tumor • APC • HIF1A • METTL3 • VIL1

Targeting of immune checkpoint regulator V-domain Ig suppressor of T-cell activation (VISTA) with 89Zr-labelled CI-8993. (PubMed, Eur J Nucl Med Mol Imaging) - P1 | "We radiolabelled and validated [89Zr]Zr-Df-CI-8993 for specific binding to huVISTA in vivo. Our results demonstrate that 89Zr-labelled CI-8993 is now suitable for targeting and imaging VISTA expression in human trials."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Pancreatic Cancer • Solid Tumor • VSIR

CI-8993-101: Phase 1 Study of CI-8993 Anti-VISTA Antibody in Patients With Advanced Solid Tumor Malignancies (clinicaltrials.gov) - P1 | N=26 | Completed | Sponsor: Curis, Inc. | Active, not recruiting ➔ Completed

Metastases • Trial completion • Oncology • Solid Tumor

CI-8993-101: Phase 1 Study of CI-8993 Anti-VISTA Antibody in Patients With Advanced Solid Tumor Malignancies (clinicaltrials.gov) - P1 | N=26 | Active, not recruiting | Sponsor: Curis, Inc. | N=50 ➔ 26

Enrollment change • Metastases • Oncology • Solid Tumor

CI-8993-101: Phase 1 Study of CI-8993 Anti-VISTA Antibody in Patients With Advanced Solid Tumor Malignancies (clinicaltrials.gov) - P1 | N=50 | Active, not recruiting | Sponsor: Curis, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Oncology • Solid Tumor

Preclinical evaluation of anti-VISTA antibody CI-8993 in a syngeneic huVISTA-KI model (SITC 2021) - P1 | "Conclusions We have validated 89Zr-Df-CI-8993 for specific binding to huVISTA in-vivo. A clinical trial of 89Zr-Df-CI-8993 is planned in solid tumour patients."

Preclinical • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

[VIRTUAL] Phase 1 Study of CI-8993 anti-VISTA antibody in patients with advanced solid tumor malignancies (SITC 2020) - P1 | "Efficacy, pharmacokinetics, pharmacodynamic and safety endpoints will be monitored and reported. Results N/A Conclusions N/A Ethics Approval The study was approved by Dartmouth-Hitchcock, Norris Cotton Cancer Center Ethics Board, approval number IRB00012031The study was approved Sarah Cannon Caner Research Institute, approval number IORG0000689"

Clinical • P1 data • Hematological Malignancies • Melanoma • Oncology • Solid Tumor • CTLA4 • PD-1

Pharmacokinetic and pharmacodynamic data from a Phase 1 Study of CI-8993 Anti-VISTA Antibody in Patients with Advanced Solid Tumors (SITC 2022) - P1 | "1 Further evaluation of the immune system and PK properties of CI-8993 will be performed as we continue enrollment to determine the RP2D. Trial Registration NCT04475523"

Clinical • P1 data • PK/PD data • Oncology • Solid Tumor • CD69 • CD8 • IL18 • IL6 • TNFA

Development of VISTA-centric tumor immunophenotyping as a novel approach for identification of potential biomarkers for anti-VISTA therapy (SITC 2022) - "Herein, we report the design, development, and analytical algorithm for comprehensive VISTA-centric tumor immunophenotyping to explore potential tumor biomarkers for novel anti-VISTA therapeutic antibody CI-8993, currently under clinical development in Phase 1 trial...We developed an algorithm for evaluation of VISTA-centric tumor immunophenotyping and demonstrated that every tumor has a unique cell-type-specific pattern of VISTA expression which could serve as a potential biomarker. Conclusions Our results demonstrate that comprehensive VISTA-centric immunophenotyping enables spatially resolved and cell-type-specific characterization of VISTA expression in solid tumors and can serve as applicable bioanalytical approach for identification of potential biomarkers to guide anti-VISTA therapeutic treatment decisions."

Biomarker • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD19 • CD4 • CD68 • CD8 • ITGAM • NCAM1 • PD-L1 • VSIR

Curis Announces Three Presentations at SITC 2022 (PRNewswire) - "Curis...announced that the Company along with its collaborative partners will be presenting three posters at the upcoming 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC 2022)....'The presentation on emavusertib follows prior research demonstrating emavusertib reaching therapeutic concentrations in brain metastases and how emavusertib might be useful in helping patients with melanoma that has metastasized to the brain by enhancing the effect of anti-PD1 therapy. Two presentations on CI-8993 describe work on our anti-VISTA antibody's pharmacokinetic and pharmacodynamic profile in the clinic and Curis's investigation of potential biomarkers to help guide therapy'."

Biomarker • Clinical data • P1 data • PK/PD data • Melanoma • Oncology • Skin Cancer • Solid Tumor

Curis Announces Date for the 2nd Annual VISTA Symposium (Curis Press Release) - "Curis...announced that the 2nd Annual VISTA Symposium will take place virtually on September 23, 9:00am-1:00pm ET....'As the global leader in VISTA development, we are honored to provide a forum for discussing the progress we're seeing with CI-8993, our own VISTA program, as well as programs from other companies and academic labs, as we collectively advance the forefront of VISTA research and development for the benefit of patients living with cancer'."

Clinical data • Oncology

SNS-101, a highly selective monoclonal antibody against the active form of VISTA, demonstrates significantly reduced cytokine release. (ASCO 2022) - "Among several non-pH-selective antibodies in clinical development, JNJ-61610588 (now CI-8993) induced dose-limiting on-target CRS at subtherapeutic dose levels and exhibited TMDD. We assessed the binding profile of SNS-101 vs. non-pH-selective VISTA antibodies. Our results demonstrate that SNS-101 does not bind to VISTA-positive cells in circulating blood."

Immune Modulation • Inflammation • Oncology • CD34

Curis Reports First Quarter 2022 Financial Results and Business Update (PRNewswire) - "Report data from the TakeAim Lymphoma study...In the first half of 2022, Report data from the TakeAim Leukemia study...In the first half of 2022, In the second half of 2022, we plan to present an update with additional monotherapy data....In the second half of 2022, we plan to present initial data for the study of emavusertib in combination with azacitadine or venetoclax. Report data from the CI-8993 (VISTA checkpoint inhibitor) study In the second half of 2022."

P1 data • P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma • Oncology

Curis Reports Fourth Quarter and Year End 2021 Financial Results (PRNewswire) - "Upcoming 2022 Planned Milestones: (i) In the first half of 2022, discuss potential for rapid registrational path for emavusertib with FDA; (ii) In the first half of 2022, report initial data for emavusertib in combination with ibrutinib in NHL; (iii) In 2022, report updated data for emavusertib in AML/MDS monotherapy; (iv) In the second half of 2022, report initial efficacy data for CI-8993 (VISTA); (v) In the second half of 2022, report initial data for emavusertib in combination with azacitadine or venetoclax in AML/MDS."

FDA event • P1 data • P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

Curis Announces Updated Data with Additional Encouraging Clinical Activity in Phase 1/2 Study of CA-4948 Monotherapy in Targeted Patients with Relapsed or Refractory AML and MDS; and Initial Clinical Data from Phase 1 Study of CI-8993 in Patients with Relapsed or Refractory Solid Tumors (PRNewswire) - P1, N=50; NCT04475523; Sponsor: Curis, Inc.; "Based on 13 patients treated in the first two dose cohorts of 0.15mg/kg and 0.3mg/kg, we believe CI-8993 has shown a promising safety profile to date, with no dose-limiting toxicities observed....In the current Curis study, CI-8993 has shown non-linear increases in pharmacokinetic (PK) exposure at each dose level and exhibits saturation kinetics, indicating the potential to overcome this sink effect as we increase dose....Curis expects to report expanded safety and tolerability data, along with initial PK, PD and anti-cancer data from the trial in the second half of 2022."

P1 data • PK/PD data • Oncology • Solid Tumor

Curis Reports Third Quarter 2021 Financial Results and Business Update (PRNewswire) - "Upcoming Planned Milestones for 2022: (i) In January, provide a clinical data update on our ongoing studies, including initial safety data from the ongoing Phase 1 monotherapy study of CI-8993 for the treatment of R/R solid tumors and the latest safety and efficacy data from the Phase 1/2 monotherapy study of CA-4948 in AML/MDS patients...; (ii) In the first half of the year, provide additional data from the ongoing Phase 1/2 monotherapy study of CA-4948 in patients with R/R AML/MDS at a medical meeting; (iii) In the first half of the year, report initial data at a medical meeting from the ongoing Phase 1/2 combination study of CA-4948 plus ibrutinib in patients with B cell cancers."

P1 data • P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

Curis Announces New Preclinical Data for CI-8993 at the Society for Immunotherapy of Cancer (SITC) Annual Meeting (PRNewswire) - "Curis, Inc...announced a poster presentation with new preclinical data for CI-8993, a first-in-class monoclonal antibody VISTA antagonist, at the Society for Immunotherapy of Cancer's 36th Annual Meeting."

Preclinical • Oncology

[VIRTUAL] Phase 1 Study of CI-8993 anti-VISTA antibody in patients with advanced solid tumor malignancies (SITC 2020) - P1 | "Efficacy, pharmacokinetics, pharmacodynamic and safety endpoints will be monitored and reported. Results N/A Conclusions N/A Ethics Approval The study was approved by Dartmouth-Hitchcock, Norris Cotton Cancer Center Ethics Board, approval number IRB00012031The study was approved Sarah Cannon Caner Research Institute, approval number IORG0000689"

Clinical • P1 data • Hematological Malignancies • Melanoma • Oncology • Solid Tumor • CTLA4 • PD-1

Phase 1 Study of CI-8993 Anti-VISTA Antibody in Patients With Advanced Solid Tumor Malignancies (clinicaltrials.gov) - P1; N=50; Recruiting; Sponsor: Curis, Inc.; Trial completion date: Jul 2022 ➔ Jul 2023; Trial primary completion date: Jul 2022 ➔ Jul 2023

Clinical • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Curis Reports Second Quarter 2021 Financial Results (PRNewswire) - "Upcoming planned milestones: By year-end 2021, report initial safety data from the ongoing Phase 1 monotherapy study of CI-8993 for the treatment of R/R solid tumors."

P1 data • Oncology • Solid Tumor

Curis Reports Fourth Quarter and Year-End 2020 Financial Results (PRNewswire) - "Upcoming 2021 Planned Milestones: Report additional clinical data from the Phase 1 study of CA-4948 in patients with AML and high-risk MDS, including patients with spliceosome mutations that encode oncogenic IRAK4-L in mid-year 2021. Report additional clinical biomarker data gathered in the Phase 1 study of CA-4948 in patients with R/R NHL in mid-year 2021. Announce initial safety and efficacy data from the ongoing Phase 1 study of CA-4948 in combination with ibrutinib in patients with R/R NHL in the second half of 2021. Report initial safety and efficacy data from the ongoing Phase 1a/1b dose-escalation study of CI-8993 for the treatment of R/R solid tumors in the second half of 2021."

P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

Curis Announces Abstract for CI-8993 Accepted for Presentation at the Society for Immunotherapy of Cancer's (SITC) 35th Anniversary Annual Meeting (PRNewswire) - "Curis...announced that a Trial in Progress abstract for CI-8993, a first-in-class monoclonal anti-VISTA antibody, has been accepted for poster presentation at the Society for Immunotherapy of Cancer's (SITC) 35th Anniversary Annual Meeting, which will be held virtually from November 9-14, 2020."

P1 data • Oncology • Solid Tumor

Clinical trial of anti-VISTA cancer antibody therapy opens for patient enrollment (Eurekalert) - "LEBANON, NH - Dartmouth and Dartmouth-Hitchcock Norris Cotton Cancer Center (NCCC) will serve as one of the lead institutions for a new multi-center clinical trial of anti-VISTA, now open and recruiting for patient enrollment. The trial is a Phase I study of CI-8993, an anti-VISTA (V-domain Ig Suppressor of T-cell Activation) antibody, in adult patients with advanced solid tumors."

Trial status

Phase 1 Study of CI-8993 Anti-VISTA Antibody in Patients With Advanced Solid Tumor Malignancies (clinicaltrials.gov) - P1; N=50; Recruiting; Sponsor: Curis, Inc.; Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Oncology • Solid Tumor