CRD3874 / Curadev - LARVOL DELTA

C92, a proton channel-blocking allosteric STING agonist generates robust antitumor activity. (PubMed, J Immunother Cancer) - "The allosteric small-molecule human STING agonist C92 that blocks STING's proton channel is significantly differentiated from orthosteric STING agonists by its unique pharmacology making it a promising immune therapeutic for the treatment of cancer."

Journal • Oncology • Oral Cancer • STING

A Study of CRD3874-SI in People With Leukemia (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center

New P1 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Systemic third generation allosteric STING agonist CRD3874-SI, a novel immunotherapy, in patients with advanced solid tumors: Results from a single-agent phase I study. (ASCO 2026) - P1 | "CRD-3874-SI has demonstrated clinical activity with manageable safety. Dose level 0.9mg/kg is biologically and clinically active. A dose expansion phase at this dose level in is planned in >5 histology specific cohorts."

Clinical • Metastases • P1 data • Adenoid Cystic Carcinoma • Gastroenterology • Gastrointestinal Disorder • Immunology • Oncology • Pulmonary Disease • Sarcoma • Solid Tumor • CXCL10

Phase I trial of CRD3874-SI, a systemically administered third generation allosteric STING agonist, in patients with advanced solid tumors (AACR 2026) - P1 | "Expansion cohorts are planned after determining the appropriate dose (RP2D).Clinical trial information: NCT 06021626. Research sponsor: Curadev Pharma, Inc."

Clinical • Metastases • P1 data • Oncology • Solid Tumor • CXCL10 • IFNB1 • STING

Epigenetic reprogramming of the STING pathway as a combination strategy in high grade serous ovarian cancer (AACR 2025) - "To determine whether this promoter-driven silencing could be reversed, we treated HRP and HR-deficient (HRD) HGSOC cell lines with increasing concentrations of DNMTi (0-100 nM decitabine, DAC)...To further evaluate STING agonist could restore functional activation of STING signaling in addition to demethylation, HGSOC cells were treated with DAC (10nM), STING agonist (CRD3874; 1μM) and combination and evaluated for downstream STING targets by western and qPCR...Together, these results demonstrate epigenetic regulation of STING expression in HGSOC, regardless of HRD status. Combining a DNMTi with a STING agonist has the potential to enhance the antitumor immune response and represents a promising therapeutic strategy for HGSOC patients."

IO biomarker • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA • CXCL10 • HRD • IL6 • TNFA • TP53

Novel allosteric STING agonists in combination with DNA methyltransferase inhibitors induce an interferon-driven apoptotic response in TP53-mutated acute myeloid leukemia (AACR 2025) - "We perfomed MTS assays in TP53-mutated and -WT AML cell lines and primary cells (N=4) treated with CPD 1 and DNMTi decitabine (DAC) combination in vitro...Treatment with the IFN inhibitor ruxolitinib or the pan-caspase inhibitor ZVAD rescued IFN-driven apoptosis. Finally CPD 1 in combination with DAC significantly reduced leukemia burden in humanized AML mouse models. These results support development of a clinical trial combining CRD3874-SI with DAC for patients with TP53-mutated AML."

Combination therapy • IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • ANXA5 • CXCL10 • CXCL11 • IFI27 • IFIH1 • IFIT2 • MX1 • OASL • STING • TNFA • TNFSF10 • TP53

The allosteric STING agonist CRD3874 is systemically tolerated demonstrates systemic tolerability (AACR 2024) - P1 | "CRD3874 is a systemically administered STING agonist with promising single agent activity and an excellent IV safety profile in NHP. An investigator sponsored FIH Phase 1 trial with CRD3874-SI has been initiated at Memorial Sloan Kettering, NY, in sarcoma, MCC patients under the supervision of Dr. Ciara Kelly (NCT06021626)."

Oncology • Sarcoma • Solid Tumor

Intravenous infusion of the allosteric small molecule STING agonist CRD3874-SI in patients with relapsed or refractory acute myeloid leukemia: A phase I trial (AACR 2025) - P1 | "Inflammasome and autophagy markers were studied in human and mouse cells. (Clinical) Patients with R/R AML are eligible for a Phase 1 clinical trial testing CRD3874-SI administered IV at six sequential dose levels, using a 3+3 design, with pharmacokinetic and pharmacodynamic correlative studies at the University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, Maryland (NCT06626633)."

Clinical • IO biomarker • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • STING

2321GCCC: CRD3874-SI in Patients With Relapsed/Refractory AML (clinicaltrials.gov) - P1 | N=6 | Suspended | Sponsor: University of Maryland, Baltimore | Active, not recruiting ➔ Suspended | Trial primary completion date: Jan 2026 ➔ Aug 2025

Trial primary completion date • Trial suspension • Acute Myelogenous Leukemia • Head and Neck Cancer • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Next generation sting agonist in combination with DNA methyltransferase inhibitors induce an apoptotic cell death mechanism driven by apoptosis in TP53-mutated Acute Myeloid Leukemia (ASH 2025) - "STING activation was also recently shown to trigger p53-independent apoptosis, andSTING agonists have shown a synergistic effect with BH3-mimetics in TP53-mutated AML cells.Here we studied the next-generation allosteric STING agonist C92 from Curadev Pharma, whichpotently binds and activates all human STING variants, in combination with the DNMTidecitabine (DAC) in TP53-mutated AML.MethodsTo test the hypothesis that DNMTis synergize with STING agonists, we treated AML cell lineswith wild-type (WT) (MOLM-14, OCI AML1) and mutated TP53 (KG1, KASUMI, U937) andpatient samples (N=5-10) with C92 in combination with decitabine (DAC)...To investigate apoptosis in TP53 KO vs WT, we measured Annexin Vlabeling by flow cytometry pre and post treatment with the 2 drugs, administered alone and incombination in the presence of the pan-caspase apoptosis inhibitor Z-VAD-FMK, the JAK/STATinhibitor ruxilitinib and the TBK1 inhibitor amlexanox...Finally, C92 and DAC combination decreased..."

Combination therapy • Epigenetic controller • IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • CXCL10 • CXCL11 • IFI27 • IFIH1 • IFIT2 • MX1 • OASL • STING • TNFA • TNFSF10

2321GCCC: CRD3874-SI in Patients With Relapsed/Refractory AML (clinicaltrials.gov) - P1 | N=6 | Active, not recruiting | Sponsor: University of Maryland, Baltimore | Recruiting ➔ Active, not recruiting | N=36 ➔ 6

Enrollment change • Enrollment closed • Acute Myelogenous Leukemia • Head and Neck Cancer • Hematological Malignancies • Leukemia • Oncology

Curadev Expands Strategic Collaboration for CRD3874-SI Through MSK Therapeutics Accelerator Program (PRNewswire) - "Curadev Pharma, Inc...and Memorial Sloan Kettering Cancer Center...are expanding their collaboration through the MSK Therapeutics Accelerator program to advance the development of Curadev's small-molecule allosteric Stimulator of Interferon Genes (STING) agonist, CRD3874-SI, to be delivered systemically to patients with advanced/metastatic cancer...The collaboration builds on the ongoing Phase 1a/b dose escalation and expansion clinical trial (NCT06021626) currently underway at MSK for sarcoma and Merkel cell carcinoma patients, and aims to explore the potential of CRD3874-SI in treating additional types of cancer. Through the MSK Therapeutics Accelerator program, MSK will provide Curadev with expertise and institutional resources, including medical, clinical, and regulatory advice, to further the development of CRD3874-SI...CRD3874-SI has demonstrated an encouraging safety and efficacy profile in a first-in-human study at MSK."

Commercial • Trial status • Merkel Cell Carcinoma • Sarcoma

2321GCCC: CRD3874-SI in Patients with Relapsed/refractory AML (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: University of Maryland, Baltimore

New P1 trial • Acute Myelogenous Leukemia • Head and Neck Cancer • Hematological Malignancies • Leukemia • Oncology • IFI27 • IFNA1 • IFNG • IL10 • IL1B • IRF7 • JUNB • NFKB2 • STAT6 • TNFA

Phase I trial of CRD3874-SI, a systemically administered STING agonist, in patients with advanced solid tumors. (ASCO 2024) - P1 | "Adverse events will be evaluated using NCI-CTCAE v5.0 criteria. This study is currently open to enrollment and dosing has commenced."

Clinical • Metastases • P1 data • Merkel Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Sarcoma • Skin Cancer • Solid Tumor • CXCL10 • STING

CRD3874-SI: a novel allosteric STING agonist with high systemic tolerability (ITOC 2024) - P1 | "This profile of retaining the high efficacy of a STING agonist while demonstrating systemic safety is unique to CRD3874-SI. Conclusions CRD3874-SI is a systemically administered novel allosteric STING agonist with promising single agent activity and an excellent IV safety profile."

Oncology • Sarcoma • Solid Tumor

Curadev Announces First Treatment Cycle Completion for the First Patient Dosed in a Phase 1a/b Clinical Trial of its Allosteric STING Agonist CRD3874-SI in Patients with Advanced Cancer at Memorial Sloan Kettering Cancer Center in New York (PRNewswire) - "Curadev...announced today a significant milestone in its development of drugs targeting the immune system to treat cancer. The dosing of patients with advanced sarcoma and Merkel cell carcinoma by intravenous infusion of Curadev's systemic allosteric STING agonist, CRD3874-SI, has been initiated in a Phase 1a/b dose escalation and expansion clinical trial currently underway at Memorial Sloan Kettering Cancer Center (MSKCC) in New York. The first 4-week treatment cycle for the first patient is complete without adverse events. The primary objective for the dose escalation is to evaluate the safety and tolerability of CRD3874-SI and to establish the maximum tolerated dose (MTD) and recommended Phase 2 dose (R2PD)."

Trial status • Merkel Cell Carcinoma • Sarcoma

Curadev's Differentiated Next Generation STING Agonist CRD3874-SI (Canada Newswire) - "Curadev is excited to introduce CRD3874, a first-in-class allosteric small molecule STING agonist, with distinct pharmacological properties that distinguish it from agents that bind to STING's cGAMP site. An intravenous formulation of this lead asset (CRD3874-SI) recently received approval from the US FDA for use in first-in-human studies in patients with advanced solid cancers."

IND • Oncology • Solid Tumor

Systemic delivery of novel, allosteric STING agonist CRD3874-SI leads to robust anti-cancer activity by generating pro-inflammatory Type I IFN signals while blocking proton channel mediated toxicity (SITC 2023) - P1 | "An investigator sponsored FIH Phase 1 trial with CRD3874-SI has been initiated at Memorial Sloan Kettering, NY, in sarcoma, MCC patients under the supervision of Dr. Ciara Kelly (NCT06021626)."

Oncology • Sarcoma • Solid Tumor • CXCL10 • GLI2

A Study of CRD3874-SI in People With Sarcoma or Merkel Cell Cancer (clinicaltrials.gov) - P1 | N=72 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center

Metastases • New P1 trial • Merkel Cell Carcinoma • Neuroendocrine Tumor • Non-melanoma Skin Cancer • Oncology • Sarcoma • Skin Cancer • Solid Tumor

Curadev Pharma receives FDA ’Study May Proceed’ Letter for its Investigational New Drug Application of CRD3874 (ANI News) - "Curadev Pharma...has received a Study May Proceed letter from the United States Food and Drug Administration (FDA) to begin a Phase 1 study of its lead STING agonist CRD3874 in advanced/metastatic solid cancers. The study will be performed at a leading US cancer center. Successful clearance of tumors by the immune system requires the action of Type I IFNs."

IND • New P1 trial • Oncology • Solid Tumor