pocenbrodib (P-300) / Novo Nordisk, Pathos - LARVOL DELTA

Probabilistic causal network models from real-world prostate cancer data identify potential synergistic combinations with CBP/P300 inhibitors (AACR 2025) - "Given that both PSMA-radioligand therapies and PARP inhibitors induce DNA damage or inhibit DNA repair, we hypothesize that these drugs in combination with pocenbrodib would lead to additive or synergistic effects by enhancing the PARPi and PSMA-radioligand efficacy via their known mechanisms of action.To validate these hypotheses, we treated a panel of 5 genetically-diverse prostate cancer PDX-derived organoids with pocenbrodib, the PARPi olaparib, and in combination. Addition of a low dose of pocenbrodib to a single dose of Lu177-PSMA617 (60 MBq) led to better tumor growth inhibition control than either single agent on its own. Mechanistic analyses from RNAseq are ongoing.Together, our integrated omics and experimental analyses support the hypothesis that combination of pocenbrodib with DNA damage-inducing or -inhibiting targeted therapies may provide further therapeutic benefit to prostate cancer patients than single agent therapies alone."

Clinical • Real-world • Real-world evidence • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA2

Targeting the AR co-activator CBP/p300 in metastatic castration-resistant prostate cancer (mCRPC) (AACR 2025) - "Purpose: Standard treatment for metastatic castration-resistant prostate cancer (mCRPC) includes androgen receptor (AR) pathway inhibitors (ARPIs), such as androgen deprivation therapy or enzalutamide. Inhibition of the CBP/p300 axis by pocenbrodib is a promising new approach to treat ARPI-resistant prostate cancer. Future studies are aimed at clinical evaluation of pocenbrodib and exploration of downstream signaling axes to identify key biomarkers of response to pocenbrodib."

Metastases • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CREBBP • FASN

Pathos AI Doses First Patient in Phase 1b/2a Clinical Trial of Pocenbrodib, a CBP/p300 Inhibitor (GlobeNewswire) - "Pathos AI...announced the first patient has been dosed in the Company’s Phase 1b/2a clinical trial evaluating pocenbrodib, a CBP/p300 inhibitor, alone and in combination with abiraterone acetate, olaparib or 177Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer (mCRPC), (P300-02-001, NCT06785636). Pocenbrodib is Pathos’ first clinical-stage asset in its pipeline....Study P300-02-001 is a multicenter, open-label, dose-finding Phase 1b/2a clinical trial to confirm the safety, pharmacokinetics (PK), preliminary antitumor activity, and pharmacodynamics (PD) of pocenbrodib alone or in combination with abiraterone acetate, olaparib or 177Lu-PSMA-617, in adults with metastatic castration-resistant prostate cancer (mCRPC). The study is expected to enroll approximately 203 patients with mCRPC..."

Trial status • Castration-Resistant Prostate Cancer

The important role of the histone acetyltransferases p300/CBP in cancer and the promising anticancer effects of p300/CBP inhibitors. (PubMed, Cell Biol Toxicol) - "Importantly, two p300/CBP bromodomain inhibitors, CCS1477 and FT-7051, as well as the dual p300/CBP and BRD4 bromodomain inhibitor NEO2734 have entered Phase I and IIa clinical trials in patients with advanced and refractory hematological malignancies or solid tumors. Taken together, the identification of p300/CBP as critical drivers of tumorigenesis and the development of p300/CBP inhibitors and proteolysis-targeted-chimaera protein degraders represent promising avenues for clinical translation of novel cancer therapeutics."

Journal • Review • Developmental Disorders • Hematological Disorders • Hematological Malignancies • Oncology • Solid Tumor • Targeted Protein Degradation • BRD4 • CREBBP

Pathos AI Closes $62M Oversubscribed Series C Round of Financing to Accelerate its Platform Approach to Drug Development (GlobeNewswire) - "Pathos AI...announced the closing of an oversubscribed $62M Series C funding round. The Series C financing round was led by New Enterprise Associates (NEA) with participation from Revolution Growth and other existing insiders....In the last 12 months, Pathos has acquired two clinical-stage precision oncology assets with plans to launch the next clinical trials in 2025. For both therapeutics, P-300 and P-500, the PATHOS platform is fueling its patient selection strategy and clinical trial design to improve the likelihood of success."

Financing • Glioma

Development of imidazo[1,2a]pyridine-based potent and selective CBP/p300 inhibitors (ACS-Fall 2024) - "The SAR we established is in good agreement with literature-reported CBP inhibitors, such as CBP30. This demonstrates the advantage of utilizing our two-step synthetic approach for inhibitor development of other bromodomains."

Oncology • BRD4 • EP300

I-CBP112 declines overexpression of ATP-binding cassette transporters and sensitized drug-resistant MDA-MB-231 and A549 cell lines to chemotherapy drugs. (PubMed, Biomed Pharmacother) - "I-CBP112 significantly reduced ABCB1, ABCC1, ABCC2, ABCC3, ABCC5 and ABCG2 in all resistant lines, as well as ABCC10 in TNBC and ABCC4 in paclitaxel-resistant NSCLC, thereby increasing intracellular drug accumulation and cytotoxicity in 2D and 3D cultures...In silico assay of ADMET properties confirmed the desired pharmacokinetic features of I-CBP112. The results suggest that the CBP/p300 inhibitor is a promising co-adjuvant to chemotherapy in drug-resistant cancer phenotypes, capable of decreasing ABC transporter expression."

Journal • Preclinical • Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ABCB1 • ABCC1 • ABCC10 • ABCC2 • ABCC3 • ABCC5 • ABCG2 • EP300

Pathos Launches Precision Oncology Pipeline With License of First Phase I Program, a CBP/p300 Inhibitor (Businesswire) - "Pathos AI, Inc...announced today that it has entered into a worldwide license agreement to develop FT-7051, a small molecule CBP/p300 inhibitor program from Novo Nordisk as Pathos’ first clinical-stage asset in its pipeline....The license will enable Pathos to continue the development of the drug and bring it to market as quickly and as safely as possible. Pathos has not yet shared specific plans for P-300 but will disclose more details during upcoming oncology conferences."

Licensing / partnership • Oncology

[VIRTUAL] Initial findings from an ongoing first-in-human phase 1 study of the CBP/p300 inhibitor FT-7051 in men with metastatic castration-resistant prostate cancer (AACR-NCI-EORTC 2021) - No abstract available

P1 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Courage: A Study of FT-7051 in Men With MCRPC (clinicaltrials.gov) - P1 | N=25 | Terminated | Sponsor: Forma Therapeutics, Inc. | N=45 ➔ 25 | Trial completion date: Mar 2023 ➔ Nov 2022 | Recruiting ➔ Terminated | Trial primary completion date: Mar 2023 ➔ Nov 2022; Sponsor Decision

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trial termination • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Forma Therapeutics Highlights Etavopivat Development Expansion and Introduces New Oncology Program from Research Pipeline at Inaugural Research and Development (R&D) Day (Businesswire) - "FT-7051 (oral CBP/p300 inhibitor) in prostate cancer: Forma’s Phase I trial continues to enroll men with metastatic castration-resistant prostate cancer (mCRPC). As of May 12, 2022, 25 patients have enrolled in the Phase I dose escalation trial, assessing the predicted efficacious exposure range supported by target engagement...Future trial enrollment to include less heavily pre-treated patients and alternative dosing schedules to address adverse events, with updated results expected in the first half of 2023...FT-3171 IND filing is expected in the first half of 2023."

IND • P1 data • Genito-urinary Cancer • Oncology • Prostate Cancer

Courage: A Study of FT-7051 in Men With MCRPC (clinicaltrials.gov) - P1 | N=45 | Recruiting | Sponsor: Forma Therapeutics, Inc. | Trial completion date: Jul 2023 ➔ Mar 2023 | Trial primary completion date: Apr 2022 ➔ Mar 2023

Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Forma Therapeutics Reports Third Quarter 2021 Financial Results and Provides Business Update (Businesswire) - “Olutasidenib results in R/R AML to be presented at ASH Dec. 11-14. Results from the Phase 2 trial will show the impact of the combination of olutasidenib and azacitidine on rates of remission and transfusion independence in patients with mutant isocitrate dehydrogenase 1 (mIDH1) AML. Analyses of safety and efficacy will be presented at the ASH annual meeting. Additional FT-7051 clinical results in mCRPC to be presented in 2022. Men with mCRPC continue to be enrolled in the dose escalation portion of the Phase 1 trial. Forma plans to present updated results from the trial at a scientific conference in mid-2022.”

P1 data • P2 data • Acute Myelogenous Leukemia • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Oncology • Prostate Cancer

Forma Therapeutics’ FT-7051 is Well-tolerated and Demonstrates Evidence of Activity in Initial Results from Ongoing Phase 1 Courage Study in Men with Metastatic Castration-resistant Prostate Cancer (Businesswire) - P1, N=45; NCT04575766; Sponsor: Forma Therapeutics, Inc; "The initial pharmacokinetic (PK) analysis of FT-7051 documented rapid absorption, which produced maximum blood concentrations within two hours. The 150 mg dose achieved drug concentrations that approached the predicted efficacious dose based on modeling with preclinical results. Skin biopsies of the men participating in the study demonstrated a reduction in H3K27AC, a marker of activity in the CBP/p300 pathway, the target of FT-7051. The majority of the treatment-emergent adverse events (TEAEs) were mild or moderate, at Grade 2 or lower, with no events leading to treatment discontinuation."

P1 data • Genito-urinary Cancer • Oncology • Prostate Cancer

[VIRTUAL] The Courage study: A first-in-human phase 1 study of the CBP/p300 inhibitor FT-7051 in men with metastatic castration-resistant prostate cancer. (ASCO 2021) - P1 | "FT-7051 is an oral, potent, and selective inhibitor of CBP/p300 with activity in preclinical models of prostate cancer including models resistant to currently used AR inhibitors like enzalutamide...Key exclusion criteria: Previous solid organ transplant, prior anticancer tx including prior tx with small molecules within 4 wks of first dose of study treatment, prior radiation tx within 4 wks prior to initiation of study treatment, prior androgen antagonist tx within 2 wks, prior radium-223 tx within 6 wks...Pt may be followed for survival for up to 24 months from last dose of study treatment . The first pt was dosed January 2021."

P1 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Organ Transplantation • Solid Tumor • Transplantation

Forma Therapeutics Reports Second Quarter 2021 Financial Results and Provides Business Update (Businesswire) - “Scientific conference presentation of initial Phase 1 FT-7051 clinical results in mCRPC. An abstract from this ongoing trial has been accepted for presentation at the NCI/AACR/EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics taking place Oct. 7-10, 2021. The presentation will include preclinical data and initial clinical results on safety, tolerability and PK/PD from patients undergoing dose escalation.”

P1 data • Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer

Forma Therapeutics Reports First Quarter 2021 Financial Results and Provides Business Update (Businesswire) - "Initial Phase 1 clinical results from FT-7051 in mCRPC anticipated later this year. This adaptive trial is assessing multiple doses of FT-7051 with dose escalation dependent upon safety and tolerability. Initial results anticipated in the fourth quarter of 2021 may include safety/tolerability, PK/PD results and preliminary biomarker data. Phase 2 registrational results of olutasidenib in R/R AML will be presented at the 2021 ASCO Annual Meeting taking place from June 4-8, 2021, and the EHA Virtual Congress taking place June 9-17, 2021."

P1 data • Acute Myelogenous Leukemia • Genito-urinary Cancer • Hematological Malignancies • Oncology • Prostate Cancer

Forma Therapeutics Reports Fourth Quarter and Year-end 2020 Financial Results and Provides Business Update (Businesswire) - “Initial Phase 1 clinical results from FT-7051 in mCRPC anticipated later this year. This adaptive trial is designed to assess multiple doses of FT-7051 with dose escalation dependent upon safety and tolerability. Initial results are anticipated in the second half of 2021, which may include safety/tolerability, PK/PD results and preliminary biomarker data. NDA being prepared for olutasidenib in R/R AML. Forma is preparing a new drug application (NDA) for submission to the U.S. Food and Drug Administration for refractory/relapsing AML patients with an IDH1 mutation. In addition, a manuscript is being prepared for publication of Phase 1 glioma results.”

NDA • P1 data • Acute Myelogenous Leukemia • Brain Cancer • CNS Tumor • Genito-urinary Cancer • Glioblastoma • Glioma • Hematological Malignancies • Leukemia • Oncology • Prostate Cancer

Forma Therapeutics Announces First Patient Dosed in Phase 1 Clinical Trial Evaluating FT-7051 for the Treatment of Metastatic Castration-resistant Prostate Cancer (mCRPC) (Businesswire) - “Forma Therapeutics Holdings, Inc…announced that the first patient has been dosed in a Phase 1 clinical trial evaluating FT-7051, a selective inhibitor of CBP/p300, a known co-activator of the androgen receptor (AR) in men with metastatic castration-resistant prostate cancer (mCRPC).”

Trial status • Genito-urinary Cancer • Oncology • Prostate Cancer

Forma Therapeutics Reviews 2020 Highlights and Outlines Key 2021 Milestones (Businesswire) - "CPB/p300 Program in Prostate Cancer: Phase 1 underway in 2021...Dosing in this trial is anticipated to begin in early in the first quarter of 2021. Forma plans to disclose initial safety, tolerability and preliminary response data in the second half of 2021."

P1 data • Oncology • Prostate Cancer

Forma Therapeutics Reports Third Quarter 2020 Financial Results and Provides Business Update (Businesswire) - “Initiation of FT-7051 Clinical Development in mCRPC: Patient enrollment in the Phase 1 trial of FT-7051 in mCRPC patients is expected to begin prior to the end of 2020. Safety and tolerability data from the trial are anticipated in 2021 and clinical activity results in 2022.”

P1 data • Trial status • Genito-urinary Cancer • Oncology • Prostate Cancer

A Study of FT-7051 in Men With MCRPC (clinicaltrials.gov) - P1; N=45; Recruiting; Sponsor: Forma Therapeutics, Inc.; Not yet recruiting ➔ Recruiting

Enrollment open • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Study of FT-7051 in Men With MCRPC (clinicaltrials.gov) - P1; N=45; Not yet recruiting; Sponsor: Forma Therapeutics, Inc.

New P1 trial • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor