inobrodib (CCS1477) / CellCentric - LARVOL DELTA

Integrated Genomic and Transcriptomic Profiling Identifies Response-Associated Transcriptional Programs in Relapsed/Refractory Multiple Myeloma Treated with Inobrodib-Based Therapy (IMS 2026) - P2 | "Ino plus pomalidomide/dexamethasone (pom/dex) is under investigation in heavily pretreated relapsed/refractory multiple myeloma (RRMM), including patients refractory to proteasome inhibitors, anti-CD38 antibodies, IMiDs, and/or BCMA-targeted therapy (NCT07096778). These findings identify activated MYC/G2M/E2F transcriptional states linked to response to ino-pom-dex therapy, with suppression following ino treatment in vitro. The data support further investigation of integrated genomic and transcriptional biomarkers associated with sensitivity and resistance to ino-based therapy, including in patients previously exposed/refractory to second-generation IMiD Pom and BCMA-targeted therapies. Larger multimodal and correlative analyses with clinical outcomes and laboratory validation are ongoing."

IO biomarker • Hematological Malignancies • Multiple Myeloma • IL6 • KMT2C • KRAS • NRAS • SDC1 • STAT3 • TNFA • TP53

Targeting P300/Cbp to Overcome Imid Resistance (IMS 2026) - " Seven MM cell lines were treated with the p300/CBP inhibitor CCS1477/Inobrodib and/or pomalidomide (Pom). These data indicate p300/CBP inhibition is effective in both IMiD-sensitive and resistant cells. Chromatin analysis suggests p300/CBP are responsible for the majority of H3K27ac in myeloma, explaining the broad sensitivity to targeting p300/CBP. Synergy of Pom and CCS1477, however, appears to be more pronounced in models that are Pom-sensitive and correlates with stronger interactions between IKZF1/3 and p300/CBP."

Hematological Malignancies • Multiple Myeloma • CREBBP • EP300 • IKZF1 • IRF4 • MYC

Protac-Mediated Cbp/P300 Degradation Targets Myeloma Cell Survival and Overcomes Macrophage-Mediated Therapy Resistance in Multiple Myeloma (IMS 2026) - "Tumour-associated macrophages (TAMs) promote MM survival and resistance to anti-myeloma therapies, including dexamethasone (Dex)...RNA sequencing from six independent experiments compared transcriptional responses to CBPD-409 and Inobrodib... CBP/p300 degradation exhibited greater anti-myeloma activity than CBP/p300 inhibition while overcoming macrophage-mediated Dex resistance. CBPD-409 directly targets MM cells while disrupting macrophage-driven BME resistance pathways, supporting further development of CBP/p300 degraders for MM."

Hematological Malignancies • Multiple Myeloma • Targeted Protein Degradation • ANXA5 • BCL2 • BCL2L1 • CCND2 • CREBBP • IRF4 • MYC

Inobrodib Treatment Synergises with Imids to Epigenetically Downregulate IRF4 Expression in Drug-Resistant Myeloma (IMS 2026) - "Standard-of-care immunomodulatory drugs (IMiDs), e.g. pomalidomide (Pom), target the TFs IKZF1/3 to the E3 ubiquitin ligase CRBN for degradation, resulting in IRF4 downregulation...The P300/CBP inhibitor Inobrodib (Ino), in combination with Pom and dexamethasone, is currently showing promise in phase IIa clinical trials for RRMM...Ino-resistant cells displayed tolerance to both Pom and the CELMoD mezigdomide, and Pom-resistant cells were tolerant to Ino... Our findings implicate epigenetic rewiring of IRF4 expression as a common mechanism of resistance to Ino and IMiDs. However, combined treatment with Pom and Ino is able to downregulate IRF4 expression in resistant cells, depending on the presence of functional CRBN. Therapeutically, this indicates that addition of Ino to Pom treatment may help resensitise IMiD-resistant RRMM patients."

Hematological Malignancies • Multiple Myeloma • Targeted Protein Degradation • ANXA5 • CRBN • IKZF1 • IRF4

Inobrodib Sensitivity in Multiple Myeloma Patients and in Cell Lines Is Associated with H3-Modifier Dysregulation (IMS 2026) - "Our results suggest Ino’s p300/CBP-mediated effects may be linked to broader H3-modifier dysregulation, particularly H3K4 alterations. OPM2, with mutant H3K4 methyltransferases, was the most sensitive in the viability assay, while H929 (H3K4 demethylase mutant) and JJN3 showed more compensatory epigenetic responses and lower sensitivity. These findings suggest that H3K4 dysregulation may be linked to p300/CBP-driven epigenetic/transcriptional pathways and share some interdependency."

Preclinical • Hematological Malignancies • Multiple Myeloma • EZH2 • HDAC1 • IRF4 • KDM5A • KDM6A • KMT2B • KMT2C • KMT2D • NSD2

DOMMINO-1: A Phase II, Open-Label, Multicenter Study of Inobrodib in Combination with Pomalidomide and Dexamethasone in Patients with Relapsed or Refractory Multiple Myeloma (IMS 2026) - P2 | "The primary endpoint is ORR per IMWG criteria assessed by IRC. The ORR and 95% confidence intervals will be calculated. Approximately 100 patients will be enrolled to have 90 patients in the efficacy evaluable set to perform the primary analysis."

Clinical • Combination therapy • P2 data • Hematological Malignancies • Multiple Myeloma • IRF4

Pharmacological inhibition of CBP sensitizes breast cancer to DNA-damaging agents by compromising DNA repair and cell cycle pathways. (PubMed, Transl Res) - "In the present study, we investigated the proteomic consequences of pharmacological inhibition of CBP in breast cancer cells using two domain-specific inhibitors, C646 (HAT domain) and inobrodib (bromodomain), and assessed their translational potential in combination with doxorubicin. Additionally, the combination of CBP inhibitors with doxorubicin did not affect the body weight or the organ indices. These findings support a rational epigenetic-chemotherapy combination approach and provide preliminary preclinical evidence for further investigation of CBP-targeted strategies to improve chemotherapy efficacy while mitigating toxicity."

Journal • Breast Cancer • Gene Therapies • Oncology • Solid Tumor • Triple Negative Breast Cancer • CASP3 • CREBBP

Combining CBP/p300 and PARP inhibitors to enhance anti-tumor efficacy in lethal prostate cancer (AACR 2025) - "In mechanistic studies, increased expression of DNA damage markers in mCRPC cells treated with CCS1477 alongside the PARPi olaparib indicated delayed DNA damage repair. Spatial transcriptomics will identify molecular signatures distinguishing responders from non-responders, advancing precision medicine in diverse populations. In conclusion, our findings indicate that CBP/p300 inhibition in combination with PARP inhibitors may have stronger anti-tumor effects than single-agent therapies, offering a promising novel therapeutic option to improve outcomes for mCRPC patients."

Clinical • Late-breaking abstract • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR

Tolerability and Clinical Activity of Novel First-in-Class Oral Agent, Inobrodib (CCS1477), in Combination with Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma (ASH 2024) - P1/2 | "The combination is tolerable, with no overt overlapping toxicity, based on the anticipated safety profile of inobrodib and pom/dex doublet. Preliminary PD data, safety and efficacy will be used to support dose expansion and dose optimisation decisions in the current study, before a pivotal trial is initiated."

Clinical • Combination therapy • IO biomarker • Anemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia • IRF4

DOMMINO-2: Inobrodib, Pomalidomide and Dexamethasone Versus Standard Available Therapy in Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P3 | N=450 | Recruiting | Sponsor: CellCentric Ltd.

New P3 trial • Hematological Malignancies • Multiple Myeloma • Oncology

Targeting CBP/p300 and its downstream transcriptional machinery in advanced prostate cancer (AACR 2023) - "CCS1477 (inobrodib) is a first-in-class bromodomain inhibitor developed by Cell Centric and targeted to inhibit CBP/p300 mediated bromodomain activity, and thus regulate cell survival...In conclusion, these studies identify CBP/p300 as a driver of PCa tumorigenesis through coordinated control of critical transcriptional events and lay the groundwork to optimize therapeutic strategies for advanced PCa via CBP/p300 inhibition, potentially in combination with AR-directed therapies. Combined, these studies have the capacity for significant near-term impact in the prevention and/or management of metastatic disease."

Metastases • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR • MYC • RAD51

Therapeutic potential of p300 bromodomain inhibition as a senescence-inducing strategy for HPV-associated oropharyngeal squamous cell carcinoma (AHNS 2026) - "In summary, CCS1477 and GNE-781 show robust anti-tumor activity in HPV16+ UMSCC47 cells, primarily through induction of cellular senescence. Our findings strongly support further evaluation of p300 BDIs as single-agent and in combination with senolytics in HPV+ model systems."

Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CDKN1A

A novel combination approach targeting P300 and DNA-PK exploits epigenetic dependencies in acute myeloid leukemia. (PubMed, Mol Ther Oncol) - "Consequently, our results show that CARM1 dependencies could also be exploited by utilizing inobrodib, a p300/CBP bromodomain inhibitor that synergizes with peposertib treatment in AML cells. Overall, these data demonstrate a rational approach for combination therapy by exploiting dependencies through inhibition of proximal effector function in addition to essential NHEJ repair, targeting its rate-limiting enzyme complex, thereby resulting in synergistic inhibition in primary AML."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

UPDATED RESULTS FROM RANDOMIZED PHASE II DOSE OPTIMIZATION STUDY OF INOBRODIB (CCS1477), IN COMBINATION WITH POMALIDOMIDE AND DEXAMETHASONE IN RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM) (EHA 2026) - P1/2 | "Methods Eligible RRMM patients had exhausted standard therapies or received ≥2 prior lines including lenalidomide and a proteasome inhibitor (if Pom-naïve). Summary/Conclusion InoPd shows manageable safety and encouraging activity in heavily pretreated RRMM, including patients previously treated with anti-BCMA therapy and/or T-cell engagers. The 20-mg dose provided the most favorable balance of safety and efficacy and was selected for the pivotal trials DOMMINO-1 and DOMMINO-2."

Clinical • Combination therapy • P2 data • Hematological Malignancies • Multiple Myeloma • Neutropenia • Thrombocytopenia

Pharmacologic inhibition of RBBP4/p300-mediated homologous recombination activity enhances glioblastoma sensitivity to temozolomide. (PubMed, Neurooncol Adv) - "Upstream regulators of the homologous recombination (HR) repair pathway are promising targets for overcoming temozolomide (TMZ) resistance. Both compounds inhibited H3K27Ac and were detectable in orthotopic tumors by LC-MS/MS and significantly extended survival alone and in combination with TMZ. These findings suggest that the RBBP4/p300-axis is a key regulator of HR-mediated repair of TMZ-induced DSBs, and inhibition by either CCS1477 or NEO2734 may be beneficial as monotherapy, but further studies are needed to determine the benefit of combining these agents with TMZ."

Journal • Brain Cancer • Eye Cancer • Glioblastoma • Oncology • Retinal Disorders • Retinoblastoma • Solid Tumor • BARD1 • BRCA1 • BRIP1 • EP300 • FIGNL1 • RAD50 • RAD51 • RBBP4

p300: expanding beyond acetylation to mastermind lactylation-dependent tumorigenesis. (PubMed, Front Cell Dev Biol) - "Furthermore, this review bridges the gap between mechanistic discovery and clinical translation by evaluating the therapeutic potential of targeting p300 lactyl-transferase activity. We highlight the emerging clinical relevance of p300 inhibitors, such as CCS1477 (in Phase I/II trials) and the preclinical agent A-485, discussing how these compounds, originally designed for acetylation or bromodomain inhibition, may be repurposed to dismantle lactylation-driven oncogenic networks and overcome metabolic immune evasion in refractory tumors."

Journal • Review • Oncology

P300/CBP inhibition with inobrodib in combination with gilteritinib and venetoclax targets leukemia stem cells in epigenetic mutant AML. (PubMed, Sci Adv) - "We find that use of the dual histone acetyltransferase p300/CBP bromodomain inhibitor CCS1477 (inobrodib), together with venetoclax and gilteritinib, virtually eliminates leukemia stem cells in an aggressive preclinical model of DNMT3A/FLT3-mutant AML by impairing pro-oncogenic survival and proliferation factors to effectively block leukemogenesis. This work identifies potential clinical utility of a targeted, triplet combination therapy for treatment of AML."

IO biomarker • Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2 • DNMT3A • FLT3

Inhibition of Acetyltransferase CBP sensitizes Breast Cancer to chemotherapy: Insights from proteomic and in vivo studies (ESMO-BC 2026) - "In the present study, we investigate the proteomic consequences of pharmacological CBP inhibition, and assess their translational potential in combination with doxorubicin. Proteomic analysis was done for breast cancer cells treated with two domain-specific CBP inhibitors, C646 (HAT domain) and Inobrodib (bromodomain). These findings support epigenetic–chemotherapy combination approach and provide a strong preclinical rationale for clinical translation of CBP-targeted strategies to improve chemotherapy efficacy while mitigating toxicity."

Preclinical • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CASP3

CellCentric Announces Oversubscribed $220 Million Series D Financing to Advance Pivotal Trials of Inobrodib in Multiple Myeloma (Businesswire) - "Proceeds will support the advancement of inobrodib through pivotal clinical development studies, including continued enrollment of the company’s recently initiated Phase 2 DOMMINO-1 study in the UK and US and initiation of the global Phase 3 DOMMINO-2 trial in the second half of 2026. Capital raised will also fund expansion of inobrodib into additional combination and maintenance treatment settings."

Financing • New P3 trial • Multiple Myeloma

p300 bromodomain inhibitors impair cell proliferation by inducing senescence in HPV positive head and neck squamous cell carcinoma (AACR 2026) - "In summary, the p300/CBP BDIs, CCS1477 and GNE-781, show anti-tumor activity in HPV16+ UM-SCC-47 cells, reactivating the p53 program and inducing senescence. These findings support further evaluation of p300/CBP BDIs in other HPV+ cancer model systems."

Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CASP3 • CDKN1A

Targeting p300/CBP abolishes HOXB13 loss-induced lipogenesis and tumor metastasis (AACR 2026) - "Loss of HOXB13 disrupts the HOXB13/HDAC3-p300/CBP balance at lipogenic enhancers, increasing H3K27ac, lipogenesis, and lipid-responsive MMPs that drive PCa invasion and metastasis. Inhibition of p300/CBP reverses these phenotypes and thus may serve as a promising therapeutic strategy for metastatic hormone-sensitive PCa with low HOXB13."

Late-breaking abstract • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR • HDAC3 • HOXB13

CBP/p300 and PARP inhibitor combination treatment synergistically enhances anti-tumor efficacy in models of advanced prostate cancer (AACR 2026) - "A Phase 1/2a study investigating a CBP/p300 inhibitor, CCS1477, alone and in combination regimens is currently underway...Our findings indicate that CBP/p300 inhibition in combination with PARPi may have stronger anti-tumor effects than single-agent therapies. Analysis of patient-derived models provides insight into the patient subsets most likely to benefit from this combination therapy, supporting its potential as a novel therapeutic approach to improve outcomes for mCRPC patients."

Clinical • Metastases • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR

Randomized Phase II Dose Optimization Study of Inobrodib (CCS1477) in Combination with Pomalidomide/Dexamethasone in RRMM (BSH 2026) - No abstract available

Clinical • Combination therapy • P2 data • Multiple Myeloma

Discovery of CBPD-409 and CBPD-268 as highly potent and orally efficacious CBP/p300 PROTAC degraders for the treatment of castration-resistant prostate cancer (AACR 2024) - "CBPD-409 exhibits strong and dose/schedule-dependent tumor growth inhibition and is more potent and efficacious than two CBP/p300 inhibitors CCS1477 and GNE-049 and the AR antagonist Enzalutamide. CBPD-268 was well tolerated in mice and rats and displayed a therapeutic index of >10. Taken together, CBPD-409 and CBPD-268 are highly promising CBP/p300 degraders for further extensive evaluations for the treatment of CRPC and other types of human cancers."

Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CRBN

Genetic or pharmacological inactivation of CREBBP sensitizes B-cell acute lymphoblastic leukemia to ferroptotic cell death upon BCL2 inhibition (AACR 2024) - "As anticipated, and validating our screen design, inhibitors of the CREBBP paralogue EP300 (the CREBBP/EP300-specific bromodomain inhibitor Inobrodib and the CREBBP/EP300 acetylase inhibitor A485) exhibited synthetic lethality, consistent with previous reports in B-cell lymphoma. Lastly, we demonstrate that small-molecule inhibition of CREBBP sensitizes B-ALL cells, regardless of genotype, to Venetoclax-induced ferroptosis in vitro and in vivo, providing a potential novel drug combination for broader clinical translation in B-ALL. In summary, we have identified a number of actionable compounds that specifically target CREBBP-mutated high-risk B-ALL, demonstrate a novel mechanism-of-action for the BCL2 inhibitor Venetoclax in B-ALL and propose CREBBP-inhibitors and Venetoclax as a novel treatment combination for B-ALL across genotypes."

IO biomarker • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CREBBP • EP300