CA-170 / Curis, Dr. Reddy’s - LARVOL DELTA

CA-170, a first in class oral small molecule dual inhibitor of immune checkpoints PD-L1 and VISTA, demonstrates tumor growth inhibition in pre-clinical models and promotes T cell activation in Phase 1 study (ESMO 2017) - P1; "These pre-clinical and preliminary clinical PD data warrant the continued clinical development of CA-170, the first oral, small molecule immune checkpoint antagonist for the treatment of advanced cancers. Dose escalation is currently ongoing (NCT02812875)."

P1 data • Colorectal Cancer • Lymphoma • Melanoma

Excellent CBR and prolonged PFS in non-squamous NSCLC with oral CA-170, an inhibitor of VISTA and PD-L1 (ESMO 2019) - P1; "Excellent CBR and PFS have been observed at 400 mg. Superior effects at 400 mg versus 800 mg dosage may likely be due to a bell-shaped response curve, previously noted in pre-clinical studies with possible activation-induced T cell death at higher doses. CA-170 also appears to have significant safety benefit, compared to IO antibodies."

Phase 1 trial of CA-170, a novel oral small molecule dual inhibitor of immune checkpoints PD-1 and VISTA, in patients (pts) with advanced solid tumor or lymphomas. (ASCO 2017) - P1; "Serial plasma, blood, and tumor samples will be collected for PK and PD evaluation. Clinical trial identifier: Clinical trial information: NCT02812875"

P1 data • Biosimilar • Hematological Malignancies

Phase 2 trial of CA-170, a novel oral small molecule dual inhibitor of immune checkpoints VISTA and PD-1, in patients (pts) with advanced solid tumor and Hodgkin lymphoma. (SITC 2018) - P1; "Conclusions To our knowledge, this is the first Phase 2 study of an oral immuno-oncology (IO) agent, showing activity in cancer patients. Updated efficacy and safety data will be presented at the meeting."

Clinical • Late-breaking abstract • P2 data • Head and Neck Cancer • Hematological Malignancies • Hodgkin Lymphoma • Lung Cancer • Lymphoma • Non Small Cell Lung Cancer • Oncology • Thoracic Cancer

Pharmacodynamic effects of CA170, a first-in-class small molecule oral immune checkpoint inhibitor (ICI) dually targeting V-domain Ig suppressor of Tcell activation (VISTA) and PD-L1 (SITC 2018) - P1; "Increased expression of VISTA in tumor biopsies were noted post CA-170 treatment. Correlation between the PD effects and tumor response to CA-170 treatment is being explored."

Checkpoint inhibition • IO biomarker • PD(L)-1 Biomarker • PK/PD data • Oncology

Phase 1 study of CA-170, a first-in-class, orally available, small molecule immune checkpoint inhibitor (ICI) dually targeting VISTA and PD-L1, in patients with advanced solid tumors or lymphomas (SITC 2018) - P1; "These data warrant the continued clinical development of CA-170. The study is ongoing with evaluation of potentially pharmacologically active BID dose in selected VISTAexpressing cancer types, such as mesothelioma."

Checkpoint inhibition • Clinical • P1 data • Gynecologic Cancers • Lung Cancer • Lymphoma • Mesothelioma • Ovarian Cancer • Thoracic Cancer

First-in-Class Small Molecule CA-170 Targeting VISTA: A Report on Efficacy Outcomes from a Cohort of 12 Malignant Pleural Mesothelioma (MPM) Patients in Study CA-170-101 (SITC 2019) - P1; "Patients had histologically-confirmed disease, >=1 prior therapy including pemetrexed-platinum doublet, no prior ICI, measurable disease per RECIST, ECOG 0-1, life expectancy >3 months, and adequate organ function. Evidence of immune-modulating activity was observed in non-clinical experiments of peripheral blood and tumor tissue specimens. Modest anti-tumor activity was observed in patients with resistant/refractory mesothelioma. CA-170 was well tolerated and shows favorable clinical PK."

Clinical

Phase 1 Study of CA-170: First-in-Class Small Molecule Targeting VISTA/PD-L1 in Patients with Malignant Pleural Mesothelioma (IASLC-WCLC 2019) - P1; "Key eligibility: histologically confirmed epithelioid, ≥1 prior therapy including pemetrexed-platinum doublet, no prior ICI, measurable disease, paired tumor biopsies if medically feasible, ECOG 0-1, life expectancy >3 months, and adequate organ function. Section not applicable"

Clinical • IO Biomarker • P1 data • PD(L)-1 Biomarker

PD-1 derived CA-170 is an oral immune checkpoint inhibitor that exhibits preclinical anti-tumor efficacy. (PubMed, Commun Biol) - "Oral administration of CA-170 resulted in increased proliferation and activation of T cells in the tumor, and significant anti-tumor efficacy in a number of immunocompetent mouse tumor models either as a single agent or in combination with approved therapeutics. These results prompted the advancement of CA-170 to human clinical trials."

Checkpoint inhibition • Journal • Preclinical • Immune Modulation • Inflammation • Oncology • PD-1

A Study of CA-170 (Oral PD-L1, PD-L2 and VISTA Checkpoint Antagonist) in Patients With Advanced Tumors and Lymphomas (clinicaltrials.gov) - P1; N=71; Completed; Sponsor: Curis, Inc.; Active, not recruiting ➔ Completed; N=300 ➔ 71; Trial completion date: Jan 2020 ➔ May 2020; Trial primary completion date: Jan 2020 ➔ May 2020

Clinical • Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Breast Cancer • Head and Neck Cancer • Hematological Disorders • Hematological Malignancies • Immune Modulation • Lung Cancer • Lymphoma • Oncology • Solid Tumor • Thoracic Cancer

New emerging targets in cancer immunotherapy: the role of VISTA. (PubMed, ESMO Open) - "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."

IO Biomarker • Journal • Review • Immune Modulation • Inflammation • Oncology • Solid Tumor • PD-1

Curis reports third quarter 2018 financial results [CA-170] (Curis Press Release) - P1, N=300; NCT02812875; Sponsor: Curis, Inc; "Curis collaborator Aurigene continues to enroll immunotherapy treatment-naïve patients in a clinical study of CA-170 at select trial sites in India....Curis expects to commence enrollment in a clinical study evaluating CA-170 in patients with mesothelioma (high VISTA expressors) in the first half of 2019 and report initial data in the second half of 2019."

Enrollment open • Enrollment status • P1 data • Mesothelioma • Oncology

An oral small molecule combination therapy targeting PD-L1, VISTA and Tim-3 immune inhibitory checkpoints exhibits enhanced anti-tumor efficacy in pre-clinical models of cancer (SITC 2017) - "These non-clinical data demonstrate a proof-of-concept showing that a combination therapy consisting of oral small molecules that antagonize the PD-L1/2, VISTA and Tim-3 pathways significantly enhance anti-tumor efficacy. CA-170 is currently undergoing Phase I clinical testing and CA-327 is in pre-clinical development. The results of our study provide a strong rational for the continued development of combination therapies using small molecule immune checkpoint antagonists for the treatment of advanced cancers."

Combination therapy • Colorectal Cancer

Muskox status, recent variation, and uncertain future. (PubMed, Ambio) - "Acknowledging uncertainties, global abundance is ca 170 000 muskoxen...Which elements are relevant for a specific population will vary, as will their cumulative interactions. Our summaries highlight the importance of harmonizing existing data, intensifying long-term monitoring efforts including demographics and health assessments, standardizing and implementing monitoring protocols, and increasing stakeholder engagement/contributions."

Journal

Curis and Aurigene announce amendment of collaboration for the development and commercialization of CA-170 (Curis Press Release) - "Curis, Inc....announced that it has entered into an amendment of its collaboration, license and option agreement with Aurigene Discovery Technologies, Ltd. (Aurigene). Under the terms of the amended agreement, Aurigene will fund and conduct a Phase 2b/3 randomized study evaluating CA-170, an orally available, dual inhibitor of VISTA and PDL1, in combination with chemoradiation, in approximately 240 patients with non-squamous non-small cell lung cancer (nsNSCLC)."

Licensing / partnership • New P2/3 trial

CA-170 - A Potent Small-Molecule PD-L1 Inhibitor or Not? (PubMed, Molecules) - "To strengthen our reasoning, we performed control experiments on AUNP-12 - a 29-mer peptide, which is a precursor of CA-170. Positive controls consisted of the well-documented small-molecule PD-L1 inhibitors: BMS-1166 and peptide-57."

Journal

Curis reports third quarter 2019 financial results (Curis Press Release) - “Curis plans to initiate a separate Phase 1 trial of CA-4948 in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), a focus on those with spliceosome mutations that encode oncogenic IRAK4-L….Curis released initial efficacy data from its Phase 1 study of CA-170 in malignant plural mesothelioma (MPM) patients…in conjunction with the Society for Immunotherapy of Cancer (SITC) 2019 Annual Meeting.The Company is presenting the results from the Phase 1 study at the SITC 2019 Annual Meeting in National Harbor, Maryland….The company will be presenting at the 61st American Society of Hematology (ASH) Annual Meeting held December 7-10, 2019 in Orlando, FL, and will provide an update on: Initial safety data from the Phase 1 study of the combination of fimepinostat and venetoclax in patients with R/R DLBCL, including patients with DH/DE lymphoma; and Updated safety and efficacy data from the Phase 1 dose escalation study of CA-4948 in patients with NHL.”

P1 data • Trial status

Curis reports second quarter 2019 financial results (PRNewswire) - "Report update of initial safety and efficacy data from the Phase 1 dose escalation study of CA-4948 in patients with NHL at an upcoming medical conference. Report initial safety data from the Phase 1 study of the combination of fimepinostat and venetoclax regimen in patients with R/R DLBCL, including patients with DH/DE lymphoma, or HGBL, in the second half of 2019. Report initial efficacy data from the Phase 1 study of CA-170 in patients with mesothelioma in the second half of 2019....Costs of royalty revenues, primarily amounts due to third-party university patent licensors in connection with Genentech and Roche's Erivedge net sales, were $0.1 million for both the second quarter of 2019 and 2018."

P1 data

Curis reports first quarter 2019 financial results (PRNewswire) - P1/2, N=180; NCT01742988; P1, N=110; NCT03328078; P1, N=300; NCT02812875; Sponsor: Curis; "For the remainder of the year, Curis expects to: (i) Report initial data on the combination of fimepinostat and venetoclax regimen in patients with R/R DLBCL, including patients with DH/DE Lymphoma, in the second half of 2019; (ii) Report initial efficacy data from its CA-4948 dose escalation study in patients with NHL in mid-year 2019; (iii) Report initial efficacy data from its CA-170 Phase 1 trial in patients with mesothelioma (high VISTA expressors) in the second half of 2019."

P1 data • P1/2 data

Curis reports fourth quarter and year-end 2018 financial results (PRNewswire) - "Curis expects to report initial data on the combination of fimepinostat and venetoclax regimen in patients with R/R DLBCL, including patients with DH/DE Lymphoma, in the second half of 2019. Curis expects to report initial efficacy data from its CA-4948 dose escalation study in patients with D/DE DLBCL in mid-year 2019. Curis expects to report initial efficacy data from its CA-170 Phase 1 trial in patients with mesothelioma (high VISTA expressors) in the second half of 2019."

Clinical data • P1 data

"$CRIS Completes Mesothelioma Enrollment in CA-170 Study https://t.co/FoLAHUko4Y" (@BioStocks)

Curis completes mesothelioma enrollment in CA-170 study (PRNewswire) - “Curis, Inc….announced that the Phase 1 study of CA-170 has reached its target enrollment of mesothelioma patients….’If the data from this phase of the trial, which is expected in the 2nd half of this year, is positive, we expect to initiate an expansion of the study.’”

Enrollment closed • P1 data

A Study of CA-170 (Oral PD-L1, PD-L2 and VISTA Checkpoint Antagonist) in Patients With Advanced Tumors and Lymphomas (clinicaltrials.gov) - P1; N=300; Active, not recruiting; Sponsor: Curis, Inc.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

CA-170: Protection of patent related to composition-of-matter until 2034 (Curis, Inc) - Corporate Presentation

Patent

A Study of CA-170 (Oral PD-L1, PD-L2 and VISTA Checkpoint Antagonist) in Patients With Advanced Tumors and Lymphomas (clinicaltrials.gov) - P1; N=300; Recruiting; Sponsor: Curis, Inc.; Trial primary completion date: Jan 2019 ➔ Jan 2020

Clinical • Trial primary completion date