Our research

How the drug works

The role of cPLA2α in cancer

There is substantial evidence that cPLA2α plays a key role in the development of cancer and inflammation. Furthermore, high cPLA2α levels correlate with metastasis and poor prognosis of several cancers. Even poor treatment outcomes of existing treatments have been shown to be correlated with high cPLA2α levels, and inhibiting cPLA2α in combination with existing standard of care treatments, for example radiation, increases the treatment response in preclinical models.

High levels of cPLA2𝝰 is associated with poor prognosis

Cytosolic Phospholipase A2 group IVA enzyme (cPLA2α) is an emerging and promising new target for treating cancers. Elevated cPLA2α expression is associated with poor prognosis and survival of cancers (red curves), as compared with patients with no or low levels of  cPLA2α expression (green curves).

AVX420 has potential as a stand alone or combination therapies

Low cPLA2α expression results in poor response in breast cancer and other cancers patients receiving hormone treatment. Inhibiting cPLA2α furthermore enhances the response to radiation therapy.

In conclusion AVX420 has a strong potential as a standalone or combination therapy.

The history of Avexxin Oncology’s drug candidate

AVX420  is a second-generation small molecule in the AVX family of potent and selective cPLA2α inhibitors1 and belongs to a chemical class of thiazolyl ketone analogues. AVX4202 was developed by professor Berit Johansen NTNU in Trondheim.

Norway and professor George Kokotos Laboratory of Organic Chemistry, University of Athens, Greece, and AVX420 is 10 times more biologically effective than the company’s previous AVX analogues.

  1. J Med Chem. 2014 Sep 25;57(18):7523-35,
  2. Hussin A, 2016, Effects of cPLA2𝝰 inhibition in the MDAMB-468 cell model system for basal-like breast cancer and/or triple negative breast cancer

    https://ntnuopen.ntnu.no/ntnu-xmlui/bitstream/handle/11250/2421056/anfal%20hussin.pdf?isAllowed=y&sequence=1 

AVX420 with a specific mode of action inhibiting cPLA2α

The small molecule AVX420 has a novel mode of action based on pioneering research on cPLA2α with a potential paradigm shift for the treatment of cancers, as a potential single agent or in combination with existing therapies. AVX420 inhibits cPLA2α resulting in significantly reduced levels of arachidonic acid, resulting in a pronounced effect on tumor growth inducing programmed cell death, anti-tumor inflammation, inhibition of angiogenesis, and anti-tumor proliferation. 

Inhibition of cPLA2α is predicted to have a therapeutic effect on cancer and inflammatory diseases via a new therapeutic intervention point. AVX analogues are both potent and selective inhibitors of cPLA2α and have demonstrated proof-of-efficacy in multiple pre-clinical disease models as well as clinical proof-of-concept in psoriasis1 and actinic keratosis2.

References: 1) Omland SH, Habicht A, Damsbo P, Wilms J, Johansen B, Gniadecki R. A randomized, double-blind, placebo-controlled, dose-escalation first-in-man study (phase 0) to assess the safety and efficacy of topical cytosolic phospholipase A2 inhibitor, AVX001, in patients with mild to moderate plaque psoriasis. J Eur Acad Dermatol Venereol. 2017 Jul;31(7):1161-1167

2) Ortner, V. K., Johansen, B., et al. The Copenhagen Actinic Keratosis Study (COAKS). A decentralised clinical trial to evaluate tolerability, safety and efficacy of daily field-directed topical treatment with cytosolic phospholipase A2 inhibitor, AVX001, in participants with actinic keratosis: protocol for a randomised controlled phase I/IIa trial. BMJ open, 12(10), 2022, e061012.

Promising data

Promising data in breast cancer models

AVX analogues have in breast cancer in vivo models shown promising tumor reducing effects in mice. In particular triple-negative breast cancer is sensitive to AVX-analogues, where an action on the tumor growth was observed but also on the vessels supplying the tumor.

 PI-3K inhibitors control the PI-3K enzyme that transmits signals in cells and that helps control cell growth. Despite being effective, they are often associated with notable side effects that can be serious or fatal, including infection, diarrhea, liver problems, rash, and inflammation of the lungs. 

Novel unpublished data have shown that AVX-analogues synergize effectively with selected PI-3K inhibitors, being able to lower the concentration of the PI-3Kinhibitor, likely to be safer for the patients and still maintain efficacy.



AVX analogue blocks effectively breast cancer tumor growth in mice (green arrow) and AVX-treated mice had absence of side effects. BEZ235 a dual PI-3K/mTOR inhibitor had similar effects, however treated mice were suffering from severe fatigue.

In the breast cancer mouse model, AVX analogue reduced the tumor blood supply by suppressing endothelial cell proliferation and tumor angiogenesis (lower panel, less yellow/orange shows reduced perfusion and blood supply).

Promising data in leukemia models

In a screen of the effect of AVX420 in 66-cancer lines, a broad anti-cancer action was observed. Apart from lung, colon, renal and other cell lines, interesting activity was seen in leukemia lines. AVX420 is very potent in selected leukemic cell lines such as acute lymphoblastic leukemia (ALL).

Novel unpublished data indicate that in an acute lymphoblastic leukemia liquid tumor animal model, where AVX420 was injected IV, a significant dose dependent effect was observed after just 3 weeks.
Very interestingly the cell viability was investigated, and programmed cell death was identified. Direct cell death by necrosis might be largely related to side effects of anticancer therapies. 

Furthermore, preliminary results show that AVX420 induces a specific form of cell death, programmed cell death, in a very low concentration range (nM) specific to human blood cancer (leukemia) cells. This sensitivity to cell death was not observed in human healthy T cells, even with a fifty-fold higher concentration of AVX420, as examined in four independent experiments.

The programmed cell death is not harmful to the host and does not provoke an inflammatory reaction, unlike another type of cell death, necrosis, which is characterized by the usual side effect profile often seen with chemotherapy. This suggests that AVX420 has selective properties against blood cancer cells and less risk of causing side effects on the healthy immune system, which is often seen with existing treatment options.

Hence, with these novel data we may see significantly less side effects in the clinic with AVX420 as compared with standard therapies. 

This is an important milestone towards further preclinical and clinical development.

The relative sensitivity of tissue type compared to panel average showed that blood cancer cell lines (green arrows, Δ10log IC50 values displayed) were highly sensitive to AVX420.

Blood cancer cells are highly sensitive to AVX420 (hematological cancers, green arrow) than for solid cancers (8.5 µM, and 19.5 µM).

Strengths and opportunities

AVX420 – is a Compound with many strengths

Our goal is to complete the pre-clinical work and initiate, phase 1 first-in-man.

The patent coverage is beyond 2040 and it includes composition of matter patent, method of use patents for cancer conditions and a new patent for a new formulation.

Further opportunities with the proprietary formulation

AVX420 is intended for intravenous administration, and a new state of the art nano formulation for AVX420 is currently being developed for clinical use in collaboration with SINTEF (a technical research institute in Norway), and where we are seeking financial support from the Norwegian Research Council. Recent and highly promising studies in leukemia with AVX420, strongly support further development of AVX420 into an efficient and safe treatment of several cancers to the benefit of patients suffering from cancer where the treatment is insufficient.

Researchers and publications

Avexxin Oncology builds on a strong Norwegian and North American scientific foundation

AXV420 is developed by prof. Berit Johansen at NTNU in Trondheim, Norway supported by several peer reviewed publications, supported by prof. Edward Dennis, UC San Diego and prof.  George Kokotos, University of Athens, Greece. The work on the role of cPLA2α  and the role of AVX analogues has extensively been investigated by prof. Berit Johansen, and prof. Bjørn Tore Gjertsen, Haukeland University Hospital, Bergen, Norway, prof.  Magne Børset, St. Olav’s University Hospital, Trondheim, Norway and prof. Joseph Bonventre, Harvard Medical School, Boston, USA. This work is supported  by strong global patents in place and with protection beyond 2040.

Avexxin Oncology’s world Leading Scientific Advisors and Key Collaborators

Professor Berit Johansen
– International Expert in cPLA2 Compounds and inventor of the AVX-compounds

Department of Biology, Faculty of Natural Sciences, Norwegian University of Science and Technology (NTNU).

Dr. Johansen is a Professor and Ph.d. in Molecular Genetics. She has a vast experience in molecular biology, inflammation, cancer research and cPLA2. Dr. Johansen did hold distinguished positions at: UCLA, US; University of Uppsala, Sweden; NTH, Department of Technical Biochemistry; at Unigen, University of Trondheim, Norway; Institute of Molecular Genetics, University of Göttingen, Germany; Biogen Research Corporation, Cambridge, MA ; Department of Chemistry and Biochemistry, University of California, San Diego, CA., and Harvard Medical School, Boston, MA, USA.

Professor Edward A. Dennis
– International Expert in PLA2

Department of Chemistry Biochemistry, University of California, San Diego, USA.

Dr. Dennis is distinguished Professor of Chemistry and Biochemistry and pharmacology, and Chair of the Department of Chemistry and Biochemistry at UCSD. The Dennis group has studied the structure and function of phospholipases for about three decades. He has contributed significantly to the AVX chemistry.

Professor Joseph Bonventre
– International Expert in Renal Diseases and PLA2

Brigham and Women’s Hospital, Renal Unit, Harvard Medical School, Boston, USA.

Dr. Bonventre is Chief of the Renal Unit and Director of the Bioengineering Division at Brigham and Women’s Hospital and has had a long-standing interest in various aspects of cellular injury and repair mechanisms in the kidney with a special emphasis on the role of inflammation, biomarkers and stem cells. One of his key focus research areas has and is still PLA2, contributing to the understanding of cPLA2𝝰 as a target.

Professor George Kokotos
– International Expert in Chemical Synthesis of PLA2 Compounds

Laboratory of Organic Chemistry, University of Athens, Greece

Dr. Kokotos is Chairman of the Department of Chemistry at University of Athens. The department is working in the field of organic, bio-organic and medicinal chemistry. Dr. Kokotos has for decades studied chemistry in order to create suitable therapeutic compounds targeting cPLA. He is a collaborator of Professor Ed Dennis in several research projects in the field, and he is co-inventor of several of Coegin Pharma’s cPLA2 inhibitors.

Professor Bjørn Tore Gjertsen
– International Expert in myeloid leukemia

Haukeland University Hospital, Bergen fMRI Group, Norway

Dr. Gjertsen is the medical chief and Consultant Hematologist. He has developed single cell phosphoprotein analysis in myeloid leukemia patient for phenotype analysis of mutations in signalling pathways, explored phosphoprotein signaling response for prognostic information in cancer, as biomarkers for therapy guidance in clinical trials and in elucidation of key physiological responses. In collaboration with Dr. McCormack, establishment of animal models and advanced molecular imaging of myelogen leukemia for development of p53- and signalling-targeted therapy, and researched AVX420 in humanized mouse models.

Professor Magne Børset
– International expert in bone marrow cancers

St Olavs University Hospital, Trondheim and Norwegian

Dr. Børset is a Norwegian physician, is a senior consultant in clinical immunology and transfusion medicine. He is doing research on molecular oncology, immunology, and cancer cells from patients with multiple myeloma – a type of cancer which is localized to the bone marrow. He has researched AVX420 in in vitro leukemia models.

Thomas Litman.

Professor Thomas Litman
– International expert in bioinformatics and multi drug resistance in cancer

University of Copenhagen, Immunology, and LEO Pharma A/S

Dr Litman is professor in bioinformatics. He holds a Master in Human Biology engineering in chemistry and a PhD in multi drug resistance, inventing the p-glycoprotein. He is affiliated as professor at University of Copenhagen and act as advisor to Columbia University, Editor in Chief of the journal Open Life Sciences, and serves as Principal Senior Scientist at LEO Pharma.

Ortner, V. K., Johansen, B., Kilov, K., Mondragón, A. C., Duvold, T., Kihl, J.R. Zibert & Haedersdal, M. The Copenhagen Actinic Keratosis Study (COAKS). A decentralised clinical trial to evaluate tolerability, safety and efficacy of daily field-directed topical treatment with cytosolic phospholipase A2 inhibitor, AVX001, in participants with actinic keratosis: protocol for a randomised controlled phase I/IIa trial. BMJ open, 12(10), 2022, e061012.

Ashcroft FJ, Mahammad N, Midtun Flatekvål H, Jullumstrø Feuerherm A, Johansen BcPLA2𝝰 Enzyme Inhibition Attenuates Inflammation and Keratinocyte Proliferation. Biomolecules. 2020 Oct 2;10(10):1402. LINK

Mahammad N, Ashcroft FJ, Feuerherm AJ, Elsaadi S, Vandsemb EN, Børset M, Johansen B. Inhibition of Cytosolic Phospholipase A2α Induces Apoptosis in Multiple Myeloma Cells. Molecules. 2021 Dec 9;26(24):7447. LINK

Feuerherm AJ, Dennis EA, Johansen B. Cytosolic group IVA phospholipase A2 inhibitors, AVX001 and AVX002, ameliorate collagen-induced arthritis. Arthritis Res Ther. 2019 Jan 21;21(1):29. LINK

Omland SH, Habicht A, Damsbo P, Wilms J, Johansen B, Gniadecki R. A randomized, double-blind, placebo-controlled, dose-escalation first-in-man study (phase 0) to assess the safety and efficacy of topical cytosolic phospholipase A2 inhibitor, AVX001, in patients with mild to moderate plaque psoriasis. J Eur Acad Dermatol Venereol. 2017 Jul;31(7):1161-1167. LINK

Kim E, Kim J, Maelandsmo GM, Johansen B, Moestue SA. Anti-angiogenic therapy affects the relationship between tumor vascular structure and function: A correlation study between micro-computed tomography angiography and dynamic contrast enhanced MRI. Magn Reson Med. 2017 Oct;78(4):1513-1522. LINK

Kim E, Tunset HM, Cebulla J, Vettukattil R, Helgesen H, Feuerherm AJ, Engebråten O, Mælandsmo GM, Johansen B, Moestue SA. Anti-vascular effects of the cytosolic phospholipase A2 inhibitor AVX235 in a patient-derived basal-like breast cancer model. BMC Cancer. 2016 Mar 7;16:191. LINK

Sommerfelt RM, Feuerherm AJ, Jones K, Johansen B. Cytosolic phospholipase A2 regulates TNF-induced production of joint destructive effectors in synoviocytes. PLoS One. 2013 Dec 12;8(12):e83555. LINK

Huwiler A, Feuerherm AJ, Sakem B, Pastukhov O, Filipenko I, Nguyen T, Johansen B. The ω3-polyunsaturated fatty acid anaolgues AVX001 and AVX002 directly inhibit cytosolic phospholipase A(2) and suppress PGE(2) formation in mesangial cells. Br J Pharmacol. 2012 Dec;167(8):1691-701. LINK