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Cancer – Chk1 kinase

Checkpoint Kinase 1 (Chk1) is the Company’s most advanced programme. It was licensed to Sierra Oncology Inc. (NASDAQ: SRRA) in September 2016. Sierra are now responsible for progressing the candidate drug through clinical trails and to the market. The clinical development candidate drug, SRA737 (formerly PNT737 and CCT245737), and other lead series compounds have shown strong potency in disease models of:

  • lung, pancreatic and colon cancers in combination with chemotherapy
  • Acute Myeloid Leukaemia (AML), B-cell lymphoma, breast cancer and paediatric neuroblastoma as a single agent
  • head and neck cancers in combination with radiotherapy

Phase 1 clinical trials of CCT245737, commenced in Q2 2016, in collaboration with the Cancer Research Technology (CRT) Pioneer Fund. These trials will ultimately target lung and pancreatic cancers in combination with standard-of-care chemotherapy, and various cancer types as a single agent. The trials are expected to complete in Q1 2018 (single agent) and Q3 2019 (chemotherapy combination).

How it works

Existing chemotherapies work by damaging the DNA of cancer cells which leads to cell death and a tumour shrinking. Many cancer cells can repair this DNA damage, therefore making the chemotherapy less effective.

A cancer cell’s ability to repair damage to its DNA depends on ‘checkpoints’ taking effect during the development of the cancer cell. These checkpoints give a tumour cell the opportunity to repair damaged DNA caused by the chemotherapy.

CHK1 therapeutics aim to disrupt specific ‘checkpoints’. This is expected to prevent cancer cells from repairing DNA damage and thus improve the extent of tumour cell death caused by chemotherapy.

Additionally, some cancers, particularly those where the cancer cells are undergoing 'replication stress' are expected to be treatable by a CHK1 therapeutic without the need for chemotherapy.

Related Items

SRA737 / PNT737 / CCT245737 Clinical Trials Information

Chemotherapy Combination Study

ClinicalTrials.gov NCT02797977

NHS Clinical Trials Gateway #35675

Cancer Research UK CRUK/16/005

Single Agent Study

ClinicalTrials.gov NCT02797964

NHS Clinical Trials Gateway #35692

Cancer Research UK CRUK/16/002

Journal Articles

Sareum/ICR Journal Medicinal Chemistry paper: "Multi-parameter lead optimization to give an oral checkpoint kinase 1 (CHK1) inhibitor clinical candidate: (R)-5-((4-((morpholin-2-ylmethyl)amino)-5-(trifluoromethyl)pyridin-2-yl)amino)pyrazine-2-carbonitrile (CCT245737)" J. Med. Chem. 2016, 59(11), 5221-5237 Abstract

Sareum/ICR Oncotarget journal paper: "The clinical development candidate CCT245737 is an orally active CHK1 inhibitor with preclinical activity in RAS mutant NSCLC and Eµ-MYC driven B-cell lymphoma" Oncotarget 2015, 7(3) 2329-2342 Abstract , Download PDF

News

CHK1 Thumbnail

Information Sheet (pdf).

Business Weekly "US deal hands Sareum share of potential $328M windfall" Link to online article 27 September 2016

News Release: Licence agreement for Chk1 inhibitor CCT245737

News Release: CHK1 Approved for Clinical Trials

Cambridge News: Sareum Helps Develop "Chemotherapy Booster"

 

 

 

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