Delving into the Latest Updates on ODM-207 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

BET

Mechanism

BET inhibitors(Bromodomain and extra terminal domain protein inhibitors)

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal DiseasesUrogenital Diseases

Active Indication-

Inactive Indication

Advanced Malignant Solid NeoplasmBreast CancerProstatic Cancer+ [1]

Originator Organization

Aurigene Oncology Ltd.

Active Organization-

Inactive Organization

Orion Oyj

Orion Corp.

Aurigene Oncology Ltd.

+ [1]

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC22H21N3O3

InChIKeyYVGWSVHZXWFLIT-UHFFFAOYSA-N

CAS Registry1801503-93-4

Cutaneous apocrine carcinoma is an extreme rare malignancy derived from a sweat gland. Histologically sweat gland cancers resemble metastatic mammary apocrine carcinomas, but the genetic landscape remains poorly understood. Here, we report a rare metastatic case with a PALB2 aberration identified previously as a familial susceptibility gene for breast cancer in the Finnish population. As PALB2 exhibits functions in the BRCA1/2-RAD51-dependent homologous DNA recombination repair pathway, we sought to use ex vivo functional screening to explore sensitivity of the tumor cells to therapeutic targeting of DNA repair. Drug screening suggested sensitivity of the PALB2 deficient cells to BET-bromodomain inhibition, and modest sensitivity to DNA-PKi, ATRi, WEE1i and PARPi. A phenotypic RNAi screen of 300 DNA repair genes was undertaken to assess DNA repair targeting in more detail. Core members of the HR and MMEJ pathways were identified to be essential for viability of the cells. RNAi inhibition of RAD52-dependent HR on the other hand potentiated the efficacy of a novel BETi ODM-207. Together these results describe the first ever CAC case with a BRCAness genetic background, evaluate combinatorial DNA repair targeting, and provide a data resource for further analyses of DNA repair targeting in PALB2 deficient cancers.

08 Dec 2020·British Journal of CancerQ1 · MEDICINE

First-in-human Phase 1 open label study of the BET inhibitor ODM-207 in patients with selected solid tumours

Q1 · MEDICINE

Article

Author: de Bono, Johann S ; Snapir, Amir ; Aspegren, John ; Postel-Vinay, Sophie ; Bono, Petri ; Korjamo, Timo ; Plummer, Ruth ; Ameratunga, Malaka ; Braña, Irene

AbstractBackgroundBromodomain and extra-terminal domain (BET) proteins are reported to be epigenetic anti-cancer drug targets. This first-in-human study evaluated the safety, pharmacokinetics and preliminary anti-tumour activity of the BET inhibitor ODM-207 in patients with selected solid tumours.MethodsThis was an open-label Phase 1 study comprised of a dose escalation part, and evaluation of the effect of food on pharmacokinetics. ODM-207 was administered orally once daily. The dose escalation part was initiated with a dose titration in the initial cohort, followed by a 3 + 3 design.ResultsThirty-five patients were treated with ODM-207, of whom 12 (34%) had castrate-resistant prostate cancer. One dose-limiting toxicity of intolerable fatigue was observed. The highest studied dose achieved was 2 mg/kg due to cumulative toxicity observed beyond the dose-limiting toxicity (DLT) treatment window. Common AEs included thrombocytopenia, asthenia, nausea, anorexia, diarrhoea, fatigue, and vomiting. Platelet count decreased proportionally to exposure with rapid recovery upon treatment discontinuation. No partial or complete responses were observed.ConclusionsODM-207 shows increasing exposure in dose escalation and was safe at doses up to 2 mg/kg but had a narrow therapeutic window.Clinical trial registrationThe clinical trial registration number is NCT03035591.

Frontiers in PharmacologyQ2 · MEDICINE

Safety and Efficacy of Bromodomain and Extra-Terminal Inhibitors for the Treatment of Hematological Malignancies and Solid Tumors: A Systematic Study of Clinical Trials

Q2 · MEDICINE

ReviewOA

Author: Sun, Yanli ; Hu, Zhenbo ; Wang, Zhanzhao ; Sun, Yanhua ; Han, Jie ; Li, Xuening

Background: The upregulated expression of BET proteins is closely associated with the occurrence and development of hematological malignancies and solid tumors. Several BET inhibitors have been developed, and some have been in phase I/II of clinical trials. Here, the safety, efficacy, and pharmacodynamics of ten BET inhibitors currently in clinical trials were evaluated.Methods: We retrieved and reviewed published reports on the clinical trials of twelve BET inhibitors including AZD5153, ABBV-075, BMS-986158, CPI-0610, GSK525762, OTX-015, PLX51107, INCB054329, INCB057643, FT-1101, CC-90010, and ODM-207 for patients with hematological malignancies and solid tumors and summarized their published target genes.Results: In the monotherapy of BET inhibitors, the most common and severe (grade ≥3) hematological adverse events (AEs) are thrombocytopenia, anemia, and neutropenia. The most common non-hematological syndromes are diarrhea, nausea, fatigue, dysgeusia, and decreased appetite, while the most severe AE is pneumonia. Additionally, Tmax of these BET inhibitors was between 0.5–6 h, but the range for T1/2 varied significantly. According to published data, the rates of SD, PD, CR and PR were 27.4%, 37.6%, 3.5%, and 5.7%, respectively, which is not very satisfactory. In addition to BRD4, oncogene MYC is another common target gene of these BET inhibitors. Ninety-seven signaling pathways may be regulated by BET inhibitors.Conclusion: All BET inhibitors reviewed in our study exhibited exposure-dependent thrombocytopenia, which may limit their clinical application. Moreover, further efforts are necessary to explore the optimal dosing schemes and combinations to maximize the efficacy of BET inhibitors.

100 Deals associated with ODM-207

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Malignant Solid Neoplasm	Phase 2	FI	Orion Corp.	22 Dec 2016
Breast Cancer	Phase 2	IN	Aurigene Oncology Ltd.	25 Oct 2016
Prostatic Cancer	Phase 2	IN	Aurigene Oncology Ltd.	25 Oct 2016
Prostatic Cancer	Phase 2	FI	Orion Oyj	25 Oct 2016
Solid tumor	Phase 2	GB	Orion Oyj	24 Jun 2016

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03035591 (BETIDES, Pubmed \| Med J Aust) Manual	Phase 1	Neoplasms	35	ODM-207	(dhwkcqlsaz) = hrombocytopenia, asthenia, nausea, anorexia, diarrhoea, fatigue, and vomiting novodjtveh (vokcbckhng ) View more	Positive	01 Dec 2020