OXC-101
Why have you chosen to focus on Acute Myeloid Leukemia (AML) as the lead indication for OXC-101?
The decision is based on OXC-101’s mode of action targeting pathways involved in the disease, thestrong preclinical support, favorable combination data with standard of care treatment for AML, theclinical responses in Phase 1, the high unmet medical need and possibility for orphan drug designation (ODD). OXC-101 is a first-in-class mitotic MTH1 inhibitor exploiting oxidative stress vulnerabilities in AML. OXC-101 offers a differentiated, mutation-agnostic approach to a disease that is difficult to treat for many subpopulations. Both FDA and EMA have approved ODD for OXC-101 in AML, giving Oxcia significant benefits, including a longer market protection.
Note 1: Hole et al, Blood 2013;122;3322-30; Sillar et al:; Int J Mol Sci 2019:20-6003; Adbel-Wahab et al., J Exp Med 2010:208:677-80; Sallmyr et al Blood 2008:111:3173-82; Zhou et al: Int J Hematol 2018:105:318 ; Jing et al., Cellular & Molecular Biology Letters 2024:29:53.
Why is high-risk MDS patients included besides AML patients in the on-going expansion cohort in the clinical trial with OXC-101?
MDS (Myelodysplastic Syndrome) is another type of blood cancer. Approximately 30% of MDS patients develop AML. The risk for developing AML is more pronounced in High-risk MDS population. OXC-101 is intended to treat patients with high-risk MDS and increased risk for leukemia.
What is the objective, overall design and patient population of the present phase I/II study?
The primary objective is to investigate the safety and tolerability of OXC-101 in escalation doses (Part 1- completed) and in combination with other anti-cancer agents (Part 2- ongoing) for the treatment ofpatients with advanced relapsed/refractory hematological malignancies. The secondary objectivesalso includes preliminary signs of clinical efficacy.
A recommended Phase 2 dose was chosen from Part 1 and used in Part 2 in combination with one of the standards of care chemotherapy treatments, an anthracycline idarubicin. Part 2 is ongoing and recruits refractory/relapsed AML with multiple prior lines of systemic therapy and relapsed high-risk MDS patients.
What is the clinical positioning and target population short, mid and long term?
OXC-101 is under development as a new treatment for refractory/relapsed AML patients who are not eligible for mutation-targeted therapies such as e.g. Flt3 inhibitors, are resistant to venetoclax treatment and/or relapsed high-risk MDS patients. Thus, heavily pretreated patients with a high unmet medical need.
The ongoing clinical trial with OXC-101 in combination with idarubicin is also a base for possible future use in newly diagnosed fit adverse risk AML patients.
New preclinical data also support a combination of OXC-101 with venetoclax-azacitidine therapy. Oxcia is planning to expand the on-going trial, combining OXC-101 with venetoclax-azacitidine therapy, thus positioning OXC-101 in first relapsed mutation agnostic, unfit AML patients.
Are there specific subgroups within AML (fit/unfit) that will benefit more or less from your treatment?
Unfit patients are a specific challenge and we think OXC-101 can be of particular value in this group with its tolerable profile. The plan is to address hard-to-treat patients, mutation agnostic, and venetoclax resistant patients as alternative or combination partner to venetoclax. Patients who initially respond to venetoclax ultimately relapse due to resistance and 30% do not respond to venetoclax-based regimens at all.
Many of the newer therapies target genetic subgroups/mutations (e.g. FLT3 inhibitors, IDH inhibitors and menin inhibitors). What are the advantages and disadvantages of a non-mutation-specific therapy?
The non-mutation specific therapies, chemotherapy and the targeted medicine venetoclax (blocking the Bcl2 protein) affect a wide range of cancer cells regardless of specific genetic mutations/oncogenes. OXC-101 is also mutation agnostic. The advantages are that it works in many patients, regardless of mutation status, there is no need for detailed genetic testing before treatment, and is particularly useful when mutations are unknown, heterogenous or evolving. Thus, no subgroup is excluded.
Cancer often contains multiple subclones with different mutations. Targeting a single mutation eg Flt3, may leave the other clones unaffected. Non-mutation-specific therapies can kill multiple clones simultaneously, reducing selective survival. The disadvantage of general therapies such as chemotherapy is that it is not cancer specific and comes with severe side effects as it also affects healthy rapidly dividing cells. However, the newer targeted non-mutation-specific therapies such as venetoclax or OXC-101, target cancer specific pathways, with potential to be less toxic than chemotherapy.
Do you expect your compound to be combined only with chemotherapy like idarubicin or also with other mutation agnostic therapies like e.g. venetoclax and/or with targeted therapy?
A combination with venetoclax, a Bcl2 inhibitor, may be beneficial. In preclinical studies it has been shown that OXC-101 show additive or even synergistic effects with other drugs enhancing oxidative stress, causing mitotic arrest or influencing apoptosis signaling such as eg Bcl2 inhibitors.
Whether OXC-101 also can be combined with mutation-specific targeted medicine such as eg Flt3 inhibitor has not yet been investigated.
What are the supporting pre-clinical data regarding efficacy?
OXC-101 has been shown to kill both AML blast and stem cells, increase survival and reduce tumor burden in AML disease models, and show additive/synergistic effects in combination treatment with anthracycline treatment (Note 2) and venetoclax.
Note 2: Sanjiv et al.,Cancer Research 2021:81:5733-5744 ; Centio et al., Mol Cancer Ther, 2022; 21:703-14.
What are the clinical data saying so far regarding efficacy and safety?
OXC-101 has shown acceptable safety and tolerability profile in phase 1. The Hematologic side effects (e.g., cytopenias) have been manageable. No chronic accumulative, renal, liver, or cardiac toxicity has been observed.
In monotherapy, efficacy signals in adverse risk patients have been demonstrated including a partial response in a heavily pre-treated patient with the hard to treat mutation TP53.
Encouraging clinical responses have been observed in the ongoing phase I/II trial in combination with idarubicin including CRi (complete remission with incomplete hematologic recovery) and bone marrow CR (Complete Response).
What is the mode of action and what are the benefits of this MoA?
OXC-101 is a mitotic MTH1 inhibitor with a unique dual mechanism of action;(1) it stops the cancer cells from dividing by disturbing microtubule polymerization, causing more oxidative stress and (2) stops the repair of oxidized DNA-building blocks by inhibiting MTH1, resulting in more DNA damage in the cancer cell, apoptosis and cell death. It is sparing healthy tissue.
It has potential to extend survival while preserving patient quality of life, including venetoclax-resistant and adverse-risk AML. Efficacy is driven by oxidative stress biology, not mutational status, thereby broadening the targetable patient population significantly.
Synergistic activity has been demonstrated with idarubicin and venetoclax/AZA, enabling flexible clinical positioning across lines of therapy. The oral administration with a manageable safety profile, supports outpatient use and sustained dosing schedules.
Is MTH1 essential for cancer cell survival?
Research suggests that many cancer cells rely on MTH1 to protect themselves from damage caused by high levels of oxidative stress. MTH1 helps remove damaged DNA building blocks, reducing oxidative DNA damage and supporting cancer cell growth.
Oxcia’s founder, Professor Helleday and his team was the first to identify MTH1 as a potential cancer treatment target.
However, to achieve adequate efficacy you also need to stop cells during mitosis and increase the DNA damage. OXC-101, a mitotic MTH1 inhibitor, does this through its dual mechanism: it both arrests cancer cells in mitosis and inhibits MTH1, increasing oxidative DNA damage and thereby killing the cancer cells.
What is the next step for OXC-101?
As next step in phase I/II, we plan to study OXC-101 in combination with Venetoclax and Azacitidine for mutation-agnostic and adverse risk (eg TP53) AML and high risk MDS.
We will also study newly Diagnosed — Fit Adverse Risk Patients who are expected to relapse.. Following successful completion of the phase I/II study, a pivotal study will be performed, with convincing data this could form basis of an early regulatory approval.
Is OXC-101 investigated in other indications?
In a collaboration with the Swedish University of Agricultural Sciences (SLU) and Karolinska Institute, the safety and efficacy of OXC-101 are being investigated in a pilot study in dogs with blood cancers such as lymphoma or hemangiosarcoma. Preliminary data is positive and shows that OXC-101 is well tolerated, and the dogs have maintained normal activity levels and quality of life. In addition, preliminary data show reduced tumor burden in lymphoma, and increased survival with no metastasis in hemangiosarcoma.
OXC-101 is also promising for psoriasis and other autoimmune diseases. Just like cancer cells, activated T cells have an altered redox status, oxidative stress, and increased levels of the DNA repair protein MTH1. Oxcia has shown that OXC-101 kills activated T cells and reduces levels of cytokines involved in e.g. psoriasis. A topical form of OXC-101 is being developed by Oxcia’s international partner for psoriasis and other dermatological indications.
Note 3: Karsten et al., Cell Death Diff 2021:29,246-261; Bivik Eding et al., J Investigative Dermatology, 2021: 141,2037-2048; Bivik Eding et al., Int.J.Mol.Sci. 2025:26(15),7174.
OXC-201
OXC-201 has important antifibrotic, anti-inflammatory and anti-virus effects, why have you chosen to focus on lung fibrosis/Idiopathic Pulmonary Fibrosis (IPF) as the lead indication for OXC-201?
There is a huge unmet need for effective and tolerable treatments in IPF and oxidative stress plays an important part as root cause. Furthermore, we saw early on promising pre-clinical data that OXC-201 had potential to stop the inflammatory and fibrosis process in IPF.
There is also possibility to obtain ODD.
OXC-201 is finalizing the pre-clinical phase in IPF. What has been demonstrated regarding efficacy and safety?
Pre-clinical efficacy data show in various studies that OXC-201 improves lung function, comparing favorably to standard treatment. Furthermore, OXC-201 shows anti-inflammatory and anti-fibrotic effects in a number of different disease models.
The pre-clinical safety program will be completed during 2026. Results so far show high tolerance of OXC-201 and that the substance is free from genotoxic effects. The safety studies will be fully analyzed and reported during 2026.
How does OXC-201 compare with current standard-of-care treatments?
OXC-201 demonstrated improved lung function in the bleomycin model, whereas nintedanib did not. In human IPF lung tissue, OXC-201 showed similar or superior effects to pirfenidone on multiple fibrosis biomarkers, supporting its potential to provide differentiated clinical benefit.
What is the next step?
Next step is investigating safety of OXC-201 in a clinical Phase I in healthy volunteers.
What is the mode of action and what are the potential benefits of this MoA and OXC-201 compared to present treatments?
OXC-201. is a small molecule that inhibits the enzyme OGG1 and constitutes a completely new treatment for pulmonary fibrosis. OGG1 regulates the cells’ response to oxidative DNA damage that occurs during oxidative stress and that affects its healing. IPF is largely driven by oxidative stress and it is a great advantage that OXC-201 is effective in specifically those conditions. By targeting OGG1, OXC-201 aims to address the root cause of IPF, not merely its symptoms.
Present treatments are inadequate both when it comes to efficacy and safety. OXC-201 has potential to improve lung function, halt the disease, protect & repair tissue as well as extending life expectancy and reducing symptoms, e.g. cough, with potential for good tolerability – thereby improving quality of life substantially.
Note 1: Tanner et al., Nat Commun, 2023;14:643.
Are there any potential disadvantages with the Mode of action?
Since OGG1 is involved in DNA repair, a theoretical concern is that OGG1 inhibition could affect genomic stability. However, this risk is considered low because DNA repair is supported by multiple overlapping repair mechanisms, allowing other enzymes to compensate for reduced OGG1 activity. Importantly, Ogg1 knockout mice are viable and do not show major effects on survival or general health under standard laboratory conditions.
Note 2: Klungland et al., Proc Natl Acad Sci USA, 1999;96:13300-13305; Tanner et al., Nat Commun, 2023;14:643.
Has OXC-201 potential in other indications?
The important role of OGG1 in the development of inflammation and fibrosis opens up opportunities in multiple diseases driven by inflammation and fibrosis, including ARDS and asthma in which OXC-201 has shown therapeutic effects. There are also next-generation OGG1 platform opportunities.
Note 3: Visnes et al., Science, 2018;362:834-839, Tanner et al., Front Pharmacol, 2022;13:999180
Can OXC‑201 impact severe symptoms in diseases like IPF?
OXC201 is designed to target OGG1, which is linked to oxidative stress and inflammation—key drivers in diseases such as IPF. By modulating this pathway, OXC201 has the potential to influence processes linked to disease progression and severe symptoms. While this is still being evaluated, the approach may offer a novel way to address aspects of IPF that are not fully controlled by current treatments. Importantly, biomarker data indicates that this mechanism may also impact pathways associated with symptoms such as chronic cough.
How well does OXC-201 treatment translate from preclinical models to human disease?
OXC-201 demonstrated consistent effects on key fibrotic pathways in both the bleomycin mouse model and human IPF lung tissue (PCLuS), supporting the translational relevance of our preclinical findings and increasing confidence in its clinical potential.