cirtuvivint (SM08502) / Biosplice Therap - LARVOL DELTA

SELNET 7.2: A Phase II trial Exploring Cirtuvivint in Certain Translocation-Related Soft-Tissue Sarcomas. (ESMO 2026) - No abstract available

P2 data • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Preliminary evidence of clinical activity from phase I and Ib trials of the CLK/DYRK inhibitor cirtuvivint (CIRT) in subjects with advanced solid tumors (ESMO 2022) - P1, P1b | "The phase Ib study combines CIRT with abiraterone acetate, FOLFIRI-panitumumab, or docetaxel in advanced/metastatic CRPC, CRC, and NSCLC, respectively...In the phase Ib combination study, in CRPC subjects that would be considered hormonal therapy resistant, we observed 2 PSA50s and 2 PSA30s among 5 subjects treated with at least 2 cycles of therapy. Conclusions Findings from these 2 studies provide evidence of clinical activity with manageable toxicity for CIRT in an advanced cancer patient population and suggest hormonal therapy resistance can be overcome in CRPC subjects when CIRT is combined with abiraterone acetate."

Clinical • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • AR • CTCs

Quantitation of Cirtuvivint (SM08502) in Human Plasma by LC-MS/MS. (PubMed, Biomed Chromatogr) - "The method has a 5-min run time and is linear from 5 to 1000 ng/mL. The assay met the criteria outlined by the US Food and Drug Administration guidance for bioanalytical method validation and will support ongoing and future clinical studies defining cirtuvivint pharmacokinetics."

Journal • CNS Disorders • Diabetes • Metabolic Disorders • Oncology

Cirtuvivint/Olaparib in Breast Cancer Susceptibility Gene/Homologous Recombination Deficiency Platinum Resistant Ovarian Cancer (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: University of Colorado, Denver | Trial completion date: Jul 2029 ➔ Sep 2030 | Trial primary completion date: Jul 2027 ➔ Dec 2029

Platinum resistant • Trial completion date • Trial primary completion date • Breast Cancer • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • BRCA

CIRTUSARC: Cirtuvivint in Selected Advanced Soft-Tissue Sarcomas (clinicaltrials.gov) - P2 | N=25 | Recruiting | Sponsor: Asociación Europea y Latinoamericana SELNET para la Investigación en Sarcomas

Trial initiation date • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Splicing disruption using a CLK inhibitor shows activity in malignant rhabdoid tumor pre-clinical models (AACR 2026) - "We hypothesized that the CLK/DYRK inhibitor SM09419, an analogue of the clinical stage CLK/DYRK inhibitor cirtuvivint/SM08502 (both developed by Biosplice Therapeutics, Inc./TenaRx, Inc.) could be active in MRT cells.METHODS. Mechanistically, CLK inhibition as monotherapy may be hitting at least two known key vulnerabilities in MRT, namely Wnt/β-catenin signaling and ncBAF function (via BRD9 misplicing). These findings provide a rationale for further early phase clinical trials of CLK inhibitors in MRT."

Preclinical • Oncology • Rhabdoid Tumor • Sarcoma • CASP3 • CASP7 • SMARCB1

The pan-CLK DYRK inhibitor SM09419 prolongs animal survival times in a subset of pediatric medulloblastoma patient-derived orthotopic xenograft mouse models (AACR 2026) - P1, P1/2, P2 | "SM09419 is a closely structurally related analog of Cirtuvivint (SM08502), another CLK/DYRK inhibitor from Biosplice Therapeutics, TenaRx, Inc., which has been studied in two completed Phase I clinical trials for treatment in adult solid tumors (NCT03355066 and NCT05084859), and is currently being studied in adults with AML or MDS (NCT06484062), Soft tissue sarcomas (NCT07032285), Ovarian cancer (NCT06856499) and Small cell lung cancer (NCT07155200).. SM09419 produced significant therapeutic efficacy a subset of MB PDOX models characterized by decreased proliferative activity. Our findings highlight the biological heterogeneity among MB subtypes and support continued investigation of splicing-modulatory CLK/DYRK inhibitors as potential targeted therapies for pediatric brain tumors."

Preclinical • Brain Cancer • Lung Cancer • Medulloblastoma • Oncology • Ovarian Cancer • Sarcoma • Small Cell Lung Cancer • Soft Tissue Sarcoma • Solid Tumor • CASP3

Combinations of Cdc-like kinase (CLK) inhibitors with targeted oncology agents or standard chemotherapy in patient-derived multi-cell type tumor spheroids (AACR 2024) - "Among the standard chemotherapeutic drugs, doxorubicin and SN-38 demonstrated additive and greater-than-additive cytotoxicity in various spheroid types when combined with either CLK inhibitor...These agents included the XPO1 inhibitor, eltanexor, the MCL-1 inhibitor, tapotoclax, the α-isoform-specific PI3K inhibitor, inavolisib, and the pan-PI3K inhibitor, copanlisib. Notably, combinations of the CLK inhibitors with the KRAS G12D variant-specific inhibitor, MRTX-1133, showed selective activity against all tumor cell lines harboring this genetic variant. Interestingly, a strong antagonistic interaction between paclitaxel and CC-671 was observed in all thirty spheroid types, while no such interaction was observed with cirtuvivint. This project was funded in part with federal funds from the NCI, NIH, under contract no. HHSN261201500003I."

Clinical • Melanoma • Oncology • Solid Tumor • KRAS

The CLK/DYRK inhibitor SM09419 shows potent efficacy across a broad panel of pediatric preclinical xenograft models - A report from the Pediatric Preclinical In Vivo Testing Consortium (PIVOT) (AACR 2025) - P1 | "SM09419 exhibited promising activity in preclinical models of TP53- and FLT3-mutated acute myeloid leukemia, and its analog cirtuvivint (SM08502) exhibited broad preclinical activity and evidence of therapeutic benefit in solid tumors. SM09419 exhibited broad antitumor activity across several pediatric cancers (e.g., ALL and NB), with activity also observed for ES and HB. Lower activity was seen in the RMS and OS models. The promising results support further evaluation of CLK/DYRK as therapeutic targets."

Preclinical • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Ewing Sarcoma • Hematological Malignancies • Hepatoblastoma • Leukemia • Neuroblastoma • Oncology • Osteosarcoma • Rhabdoid Tumor • Rhabdomyosarcoma • Sarcoma • Solid Tumor • Wilms Tumor • FLT3 • TP53

CIRTUSARC: Cirtuvivint in Selected Advanced Soft-Tissue Sarcomas (clinicaltrials.gov) - P2 | N=25 | Recruiting | Sponsor: Asociación Europea y Latinoamericana SELNET para la Investigación en Sarcomas

Trial initiation date • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Cirtuvivint inhibits Ewing sarcoma (ES) growth by suppressing EWS-FLI-1 expression and inducing alternate EWS-FLI1 splice variants (AACR 2025) - "Treatment of ES cells (A673, CHP100, and MHH ES1) with increasing concentrations of cirtuvivint, as well as its analog SM09419, significantly reduced cell viability (LD50 ~250 nM) both in vitro and in vivo, This treatment suppressed EWS-FLI-1 expression and generated multiple alternative EWS-FLI-1 variants within 4-6 hours, marked by the loss of whole exons. Mechanistic studies showed reduced β-catenin and c-myc expression, however, siRNA experiments targeting these genes did not affect cell growth. To investigate the role of these alternative EWS-FLI1 splice variants, transcripts generated by cirtuvivint treatment were cloned, sequenced, and inserted into eukaryotic expression vectors, including a Tet-inducible system and vectors for cell-free protein expression."

Ewing Sarcoma • Oncology • Sarcoma • Solid Tumor • CDK1 • CTNNB1 • EWSR1 • FLI1 • MYC

Development of orally bioavailable multi-targeted inhibitors of Wnt signaling for the treatment of colorectal cancer (AACR 2025) - "Our lead compound, DYR895, demonstrates improved Wnt signaling inhibition over phase 1b clinical candidate Cirtuvivint (WNT reporter EC50: 5.1 nM vs. 230 nM), while being well tolerated in mouse models (MTD >50 mg/kg) and orally bioavailable (F%: 81%)...Further optimization of DYR895 with the goal of reducing CNS exposure while enhancing Wnt inhibition led to the discovery of DYR1055, with a 10x improvement in affinity for some target kinases while maintaining key surrogate ADME attributes. Investigations into the efficacy of DYR1055 in disease models are ongoing."

Colorectal Cancer • Oncology • Solid Tumor • BRAF • CDK7 • PIK3CA

Dynamic switching of apoptosis-modulating BIM heterodimers in response to BH3 mimetics in xenograft models of hematologic malignancies. (PubMed, Mol Cancer Ther) - P1 | "Our results elucidate quantitative pharmacodynamics of S63845, venetoclax, and cirtuvivint, an agent that is currently being evaluated with venetoclax to treat AML (NCT06484062). Compensatory increases in off-target Bim heterodimer levels in response to either S63845 or venetoclax offer a possible mechanism of clinical drug resistance."

Journal • Preclinical • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Oncology • BCL2 • BCL2L1 • CASP3 • MCL1

Aberrant splicing in Ewing sarcoma: Preclinical evaluation of SM08502 in combination with vincristine and biomarkers of response (Sarcoma-RC 2026) - "Legal entity responsible for the study The authors. Funding Has not received any funding."

Combination therapy • Preclinical • Ewing Sarcoma • Sarcoma • Solid Tumor • EWSR1 • FLI1

Small Cell Lung Cancer Irinotecan and CDC2-like Kinase Inhibition Trial (SLICK Trial) (clinicaltrials.gov) - P1/2 | N=42 | Recruiting | Sponsor: Washington University School of Medicine | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Biosplice Therapeutics Announces First Patient Dosed in Investigator‑Initiated Phase 1 Clinical Trial of Cirtuvivint and Olaparib in BRCA/HRD Platinum‑Resistant Ovarian Cancer (The Manila Times) - "The investigator-initiated trial, 'Cirtuvivint and Olaparib for the Treatment of Patients with BRCA/HRD Platinum Resistant Ovarian Cancer' (NCI-2024-09126; NCT06856499), is sponsored by UCHealth University of Colorado Hospital and led by principal investigator Bradley R. Corr, MD, associate professor and director of clinical research in gynecologic oncology at the University of Colorado Anschutz."

Platinum resistant • Trial status • Ovarian Cancer

Trial in progress: A phase I study evaluating the safety of cirtuvivint (CIRT) as monotherapy and in combination with ASTX727 in patients with myelodysplastic syndromes (MDS) and Acute Myeloid Leukemia (AML) (ASH 2025) - P1 | "Outcomes afterresistance to venetoclax-based therapy are particularly poor with a median OS of 2.5 monthsindependent of the type of salvage therapy used (Maiti et al., Haematologica 2020). ConclusionsThis phase I trial will establish the safety and RP2D for CIRT as monotherapy in R/R AML or R/R MDS(cohort I and II) and in combination with ASTX727 for untreated higher-risk MDS (cohort III). The trial isactively recruiting and aims to inform future phase II studies."

Clinical • Combination therapy • Monotherapy • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Solid Tumor • XIAP

SM08502-Mediated β-Catenin Repression Synergizes with Olaparib to Inhibit Tumor Progression. (PubMed, Cancer Res Commun) - "Overcoming PARPi resistance will provide patients with therapeutic options. The study shows, in the context of resistant disease, the potential of targeting CDC-like kinase/dual-specificity tyrosine phosphorylation-regulated kinase alone and in combination with PARP inhibitors."

IO biomarker • Journal • Oncology • BRCA1 • BRCA2 • CTNNB1 • HRD • PD-1 • PD-L1

CIRTUSARC: A multicenter, open-label phase II trial of cirtuvivint as second-line therapy in selected advanced soft-tissue sarcomas (ESMO 2025) - "A single-stage design (n=25 evaluable) tests PFSR-3m ≥70% vs. ≤45% (α=0.05, β=0.20). The trial is enrolling at 8 centers in Spain."

Clinical • Metastases • P2 data • Ewing Sarcoma • Liposarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Synovial Sarcoma

Cirtuvivint/Olaparib in Breast Cancer Susceptibility Gene/Homologous Recombination Deficiency Platinum Resistant Ovarian Cancer (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: University of Colorado, Denver | Not yet recruiting ➔ Recruiting

Enrollment open • Platinum resistant • Breast Cancer • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • BRCA

RNA processing kinase inhibitors and epigenetic inhibitors in combination with oncology drugs or investigational agents in multi-cell type patient-derived tumor cell line spheroids. (PubMed, Cancer Chemother Pharmacol) - "These findings may provide guidance for development of clinical trial combination regimens including cirtuvivint, CC-671 or iadademstat. Full data sets are available on PubChem."

IO biomarker • Journal • Preclinical • Oncology • Targeted Protein Degradation • KRAS

Biosplice Therapeutics Announces First Patient Dosed in NCI-Sponsored Clinical Trial of Cirtuvivint in Acute Myeloid Leukemia and Myelodysplastic Syndromes (GlobeNewswire) - "The trial (NCT06484062) is evaluating the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of cirtuvivint, both as a monotherapy and in combination with ASTX727 (INQOVI, oral decitabine/cedazuridine)..."

Trial status • Acute Myelogenous Leukemia • Myelodysplastic Syndrome

DYR895: An orally bioavailable, brain-penetrant small molecule kinase inhibitor for simultaneous targeting of cancer growth and stemness (ACS-Fall 2025) - "The compound is orally bioavailable, well-tolerated, and exhibits excellent brain penetration with minimal efflux. Despite its multi-targeted nature, DYR895 remains relatively selective within the kinome, outperforming reference compounds cirtuvivint and abemaciclib."

Brain Cancer • Colorectal Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • FLT3

Small Cell Lung Cancer Irinotecan and CDC2-like Kinase Inhibition Trial (SLICK Trial) (clinicaltrials.gov) - P1/2 | N=42 | Not yet recruiting | Sponsor: Washington University School of Medicine

New P1/2 trial • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

CIRTUSARC: Cirtuvivint in Selected Advanced Soft-Tissue Sarcomas (clinicaltrials.gov) - P2 | N=25 | Recruiting | Sponsor: Asociación Europea y Latinoamericana SELNET para la Investigación en Sarcomas

New P2 trial • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor