We are currently working on
Oxcia is currently engaged in development or commercialization of projects concerning the following targets:
In the end of 2016, the Medical Product Agency (MPA) approved a clinical phase 1 trial, MASTIFF (MTH1, A phase)
I, Study on Tumors Inhibition, First in human, First in class with EudraCT no: 2016-002624-80), investigating safety and tolerability of Karonudib in cancer patients with advanced solid malignancies. Thomas Helleday Foundation for Medical Research is the sponsor of the MASTIFF trial, but has appointed Oxcia AB to assist in the clinical development and commercialization.
Many cancers have a dysfunctional redox status and upregulated levels of MTH1, suggesting that MTH1 is necessary for the cancer cell to survive the high load of oxidative stress and oxidized nucleotides. MTH1 (NUDT1) is a sanitizing enzyme, hydrolysing oxidized nucleotides into their monophosphates, thereby hindering them to be incorporated into DNA and cause mutations (Nakabeppu et al., 2010). By knocking down MTH1, cancer cells can no longer survive, while normal cells still divide and live (Gad et al., Nature 2014; Rai et al., 2011, Ling et al., 2016 etc). In Professor Thomas Helleday laboratory at Karolinska Institute, small molecule inhibitors against MTH1 was identified and shown to kill a variety of cancer cells in vitro and reduce tumour growth in mice xenograft disease models (Gad et al., Nature 2014; Warpman Berglund et al., Annals of Oncology 2016).
Oxcia AB has been crucial for patent strategies and clinical development strategies for the MTH1 project. Oxcia AB has, been responsible for planning, preparing, initiating the clinical trial MASTIFF, and are now managing it according to GCP, GMP, GLP and applicable regulations.)
OGG1 is an enzyme in the base excision repair (BER) pathway that excises 8-oxoguanine (8-oxoG) paired opposite cytosine. Since mice)
lacking OGG1 are largely healthy, but resistant to a range of inflammatory stimuli (Mabley et al 2006, FASEB J, Touati et al 2006, Helicobacter, Li et al 2012, Free Radic. Biol. Med., Bacsi et al 2013, DNA Repair), the team in Professor Thomas Helleday's laboratory decided to further investigate the involvement of OGG1 in the regulation of inflammation. OGG1 inhibitors are also evaluated as adjuvants for the treatment of cancer.
Oxcia AB is appointed to assist in patent and commercial strategies as well as for the preclinical development of OGG inhibitor for several indications.)
Patients suffering from MDS and AML are often resistant to anticancer therapy. The introduction of cytidine analogues like 5-Azacytidine (5AC))
and 5-aza-2´-deoxycytidine (5-AdC) in clinical regimes has improved best supportive care, yet many patients remain unresponsive to treatment due to resistance or toxicity and relapse into disease. The DCTPP1 enzyme is a resistance mechanism against 5AC and 5-AdC treatment. DCTPP1 converts the active triphosphate forms of cytidine analogues to the inactive monophosphate forms, resulting in an inefficient treatment. An inhibitor of DCTPP1 will render cancer cells more sensitive to 5AC and 5-AdC treatment.
In Professor Thomas Helleday laboratory at Karolinska Institute, DCTPP1 inhibitors were identified, developed and shown to enhance the cytotoxic effect of cytidine analogues in cancer cells but did not show toxic effect in non-malignant primary cells. Proof-of-concept studies in mice and co-crystal structure of the lead compound bound to the active site of the enzyme have been performed.
Oxcia AB is assigned to assist in patent and commercial strategies for the project. Oxcia AB aims at outlicensing the project with the first inhibitors of the pyrophosphatase dCTPase (DCTPP1) protein as a novel combination therapy for patients suffering from myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).)
Breast cancer represents the most common cancer in women and is a leading cause of cancer-related death in Sweden and)
globally. Most breast cancers use hormones (estrogen and progesterone) to promote the growth of the tumor (so-called hormone receptor positive (HR+) breast cancers). This process requires vast amount of cellular energy in the form of adenosine triphosphate (ATP) which allows the cancer cell to respond to hormone stimulation.
NUDT5 protein allows the cancer cell to produce large amounts of ATP following hormone stimulation. This molecular energy fuels the production of hormone-dependent genes which tells the cancer cell to proliferate. Without NUDT5, hormone-dependent gene expression is blocked, which halts the growth response following hormone stimulation in breast cancer cells.
Together, the Helleday and Page Laboratories at the Karolinska Institute have developed potent NUDT5 inhibitors that have promising effects against breast cancer cell lines. These compounds were designed to specifically bind to NUDT5 in cancer cells using state-of-the-art chemical biology techniques, with a concerted effort to avoid cytotoxic and off-target effects. Lead NUDT5 inhibitors have been formulated for in vivo testing, have excellent pharmacokinetic properties and are well-tolerated in repeated dose mouse studies. Ongoing efforts aim to show proof of concept in mouse breast cancer models.
Oxcia AB is working collaboratively with the Karolinska Institute Innovation Office to assist in commercial strategies for the project. The aim is to outlicense the project with the first inhibitors of the NUDT5 protein representing promising anti-cancer agents that could help treat and prevent the recurrence of breast cancer in patients.)