Pre-clinical

Artios is a leading DNA Damage Response (DDR) company focused on developing first-in-class treatments for cancer.

Overview – Leading DDR innovation

Artios is a leading DNA Damage Response (DDR) company focused on developing first-in-class treatments for cancer. Cancers change their DDR pathways to allow mutations in their DNA so that they can evolve and adapt. This helps cancers to become resistant and overcome many current therapies. Targeting the remaining DDR pathways has been proven to selectively kill cancer cells through a concept known as 'synthetic lethality'. Artios has in-licensed its lead DDR programme, Pol theta (Polθ)', from Cancer Research UK (CRUK). As an early investor in Artios, Arix continues to work with Artios' visionary team to build a world-leading DDR company and create significant value for both patients and investors. Arix first invested in Artios during the Series A in 2016, along with other VC investors. Following Artios' £65m Series B financing round, Arix is now the company's largest shareholder.

Team – Management team with a proven DDR track record

Artios' experienced leadership team is led by Niall Martin, CEO, who played a key role in identifying Lynparza™ (olaparib). He is supported by a scientific research and development team with vast experience in DDR and drug discovery.

  • Niall Martin, Chief Executive Officer
  • Graeme Smith, Chief Scientific Officer
  • Andrew Muncey, Chief Financial Officer and Company Secretary
  • Ian Smith, Chief Medical Officer
  • Peter Harris, Clinical advisor
  • Simon Boulton, VP of Scientific Strategy
  • Harry Finch, Medicinal Chemist advisor

Market potential

40-50% cancers are potentially DDR targetable and the clinical potential for DDR therapeutics is broad:

  • Novel synthetic lethalities
  • PARP inhibitor resistance (innate and acquired)
  • DDR-PARP inhibitor combinations
  • DDR-IO combinations
  • IR and DNA damaging combinations

DDR explained

DNA Damage Repair (DDR) is a vital process that helps cells survive and replicate. No cells, including cancer cells, can survive without DNA repair. Cancer cells however, like to rely on secondary DNA repair processes and this results in them being more mutational or unstable. Changes in a cancer cell's DNA repair processes are part of its development into a more advanced disease.

These changes can also become a cancer cell's Achilles' heel. Cancer can become much more reliant on alternative DNA repair processes in order to survive. Inhibitors to these retained DNA repair pathways, like Polθ, can selectively kill cancer cells through synthetic lethality.

Some of the mutational changes in DNA that drive tumour evolution can also lead to resistance to current treatments, as the cell starts to use alternative or reactivated DNA repair pathways. This kind of resistance can occur against many known DNA damaging agents and new DDR inhibitors like PARP inhibitors. As such, identifying other potential targets in the DDR processes could have significant impact on treating cancers in the future – both through use as a single agent and in combination approaches designed to limit resistance.

Novel technology – Pol theta (Polθ) – a major new DDR target to rival PARPi

Artios set out to identify and exploit novel protein classes across the DDR pathways. Polθ and the company's second and as yet undisclosed lead programme, represent two DDR targets that control key aspects of DNA repair. Mechanistically, these programmes have the ability to kill cancer cells as single agents, or to sensitise cancer cells to radiotherapy and other DNA-damaging agents, including novel treatments, such as PARP inhibitors or immunotherapies.

DNA polymerase theta (Polθ) is involved in multiple processes associated with DNA repair. Polθ expression is low in normal tissues but it is up-regulated in a number of tumour types such as breast, ovarian, HNSCC and lung. As such, Polθ inhibitors have the potential to be used in a broad range of clinical settings, specifically HR-deficient tumours such as breast and ovarian cancer, or in combination with DNA-damaging agents – chemotherapy and radiotherapy.

Pipeline

Artios has a leading position in developing Polθ drugs and a strong pipeline of DDR programmes in early discovery-

2018

2019

2020

2021

2022

2023

Polθ (Polymerase theta)

Clinical candidate selection (LO)

Pre-clinical candidate selection IND evaluation

FIH Phase 1b SL efficacy in novel gene

Phase Ib SL efficacy in novel gene

SL efficacy in HRD

Combination + PARPi, IR

Targets 2, 3 and 4

Hit to lead

Clinical candidate selection (LG/LO)

Pre-clinical candidate IND evaluation

FIH Phase 1a MAD/SAD

Programmes underpinned by a strong DDR platform

Research

Translational

Development

Scientific validation

DDR has been clinically validated by the first-generation PARP inhibitors currently on the market. They are being commercialised by multi-$bn market capitalised companies including AstraZeneca, Tesaro (GSK), Pfizer and Clovis Oncology.

Achieved and expected milestones

  • Strong pipeline of several DDR programmes in early discovery
  • Completed $84m Series B financing to drive Polθ and other programmes to clinic by 2020/2021
  • IND application in H2 2020
  • Financed out to the end of 2023