APAXEN – BREAKTHROUGH THERAPIES FOR CHRONIC INFLAMMATORY DISEASES WITH A PRIMARY FOCUS IN PULMONARY ARTERIAL HYPERTENSION (PAH)

BREAKTHROUGH THERAPIES FOR
PULMONARY ARTERIAL HYPERTENSION

About Us

Apaxen is a privately-held biotechnology company whose mission is to bring innovative treatments to patients in a wide range of therapeutic indications related to chronic inflammation, with a primary focus in pulmonary arterial hypertension (PAH) and other deadly pulmonary diseases.

The Company is specialized in the discovery and development of first-in-class small molecule inhibitors of pleiotropic pro-inflammatory cytokine “Macrophage migration Inhibitory Factor (MIF)”, a crucial regulator of innate immune responses. Apaxen’s lead compound, MFC-1040, an orally bioavailable and selective small molecule MIF inhibitor, is being developed for the treatment of pulmonary arterial hypertension (PAH), a rare and fatal disease, with a strong medical need since approved treatments are symptomatic and associated with low median survival.

MFC-1040 has a unique mechanism of action and has the potential to revolutionize the standard of care of PAH and other diseases related to chronic inflammation.

Apaxen has its headquarters in Gosselies (Belgium), at the Biopark Charleroi Brussels South.

TEAM

MANAGEMENT TEAM

Bart Wuurman
Chief Executive Officer

Bart is an accomplished biotech CEO with over 30 years’ experience in innovative drug development, biotech financing, business development and licensing. He has extensive experience in working with research and development based companies in pharmaceutical product development in several therapeutic areas, including cancer, fibrosis and cardiovascular diseases. Bart Wuurman has previously executed successful biotech company exits in the UK and in the Netherlands. He was responsible for pharma licensing deals worth over $700 million. Bart was CEO of De Novo pharmaceuticals (UK), AM-Pharma, Lanthio Pharma and is Director of Lyramid (Australia) and Hercules Pharmaceuticals. Before joining Apaxen, Bart was also Managing Director of DDF Ventures, a life-science focused venture fund with a portfolio of start-up companies in The Netherlands.

Mathilde Metna
PhD – Pre-Clinical Director

Mathilde has more than 10 years of experience in R&D, both in academic and industrial environments. Before joining Apaxen, Dr Metna performed lead selection and PoC efficacy studies on new chemical entities currently at clinical stages. She managed ADMET, IND-enabling preclinical studies and prepared regulatory submissions to the FDA and EMA. Neurobiologist by background, she focused on the understanding of cannabinoid receptors physiology in the brain at the INSERM Neurocentre Magendie (Bordeaux, France). Her research works have led to more than a dozen publications and she is co-inventor and co-author of several patent applications. As one of the first employees, she was instrumental to the success of Aelis Farma.

Olivier Favre-Bulle
PhD – CMC Director

Olivier has 20 years experience working in the life sciences industry, firstly as a researcher and later as a business leader. He began his career at Rhône-Poulenc, before moving to Covance, and later to Novo Nordisk. He has set up and developed several biotechnology companies and is founder and director of 3BioTech, a pre-clinical and clinical trial service provider. As a researcher and developer, he has over 20 patents bearing his name and has won the Rhône-Poulenc research prize. He has directed several international industrial development projects from inception in the laboratory through to cGMP production. He holds a degree in chemical engineering, supplemented by a PhD in molecular and cell biology from the University of Groningen (the Netherlands). He has also received a MBA from SIMI (Denmark).

ADVISOR

Enrico Bastianelli
Founder
MD, MBA – Strategic Advisor

Dr Bastianelli has acquired a broad pharma/biotech industry experience in fields such as research & development, production, business development, marketing and strategy. He started his career in the Pathology Department of the Erasmus University Hospital in Brussels, Belgium, before joining Procter & Gamble Pharmaceuticals in Marketing in 1996. In 1999, he went on to become a Consultant for McKinsey & Co, where he spent most of his time on strategic and organizational missions for major pharmaceutical as well as for biotechnology companies all over Europe. From its creation in 2002 until mid-2006, Dr Bastianelli has worked as VP Corporate Development for ProSkelia, the Aventis spin-out focused on bone diseases and hormone disorders, who became ProStrakan, after the merger with Strakan, a Scottish specialty pharma company. Between June 2006 to October 2016, Enrico Bastianelli has been the founder and Chief Executive Officer of Bone Therapeutics, a Belgian-based cell therapy company specialized in bone diseases. Started with 3 employees, Enrico Bastianelli turned Bone Therapeutics into a late (phase III) clinical stage publicly listed company strong of over 100 highly qualified people. Since 2017, he is the Chief Executive Officer of Graftys, one of the world leaders in resorbable bone cements.

DISEASES

Pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a rare, chronic and life-threatening disease characterized by an abnormal and progressive increase in blood pressure in the small pulmonary arteries leading ultimately to right heart failure and death.

This increased blood pressure is caused by the narrowing of the small pulmonary arteries which are the blood vessels that carry blood from the right side of the heart through the lungs. PAH has an estimated prevalence in Europe of 15–60 cases per million.

There is currently no cure for PAH. Available therapies are agents that focus on improving the vasoconstriction-vasodilation balance without addressing the underlying cause of the disease. As a result, five-year median survival which is nearly 57% remains low despite treatment. Although the exact mechanisms leading to the onset and progression of PAH are still not yet fully understood, increasing scientific evidence points towards an inflammatory component underlying PAH.

Idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a rare, chronic and life-threatening disease in which the tissues of the lungs become progressively thick and stiff.

As a result of thickening of lung tissues, brain and other organs are unable to receive optimum oxygen. There is no cure for IPF. The clinical prognosis of patients with IPF remains poor as the median survival at diagnosis is 2 to 5 years.

Importantly, pulmonary hypertension (PH) is considered as one of the principal predictors of mortality in patients with IPF. Although current treatment options are available, they don’t improve lung function, and the disease continues to progress in the majority of patients.

Therefore, there is still significant unmet medical need in IPF.

SCIENCE

PIPELINE

Apaxen has a robust pipeline of products at discovery and preclinical stages of development for the treatment of diseases associated with chronic inflammation. Pulmonary arterial hypertension (PAH) and other deadly pulmonary diseases are the primarily targeted indications.

Apaxen has acquired all intellectual property rights (incl. patents, data..) on the anti-MIF technology of Mifcare (France), including patent families protecting MFC1040 and its uses.
Two family of patents have been issued in the US (US 10,160,732 and US 10,071,080), Europe (EP 2929882 and EP 2944310) and Hong-Kong (HK 1216234 and HK 1217299). The remaining patents to be issued in Japan are pending.

Apaxen has currently four R&D programs, including three based on MFC-1040:
• MFC-1040 for the treatment of PAH, currently in preclinical phase
• MFC-1040 for the treatment of pulmonary hypertension secondary to idiopathic pulmonary fibrosis (IPF), currently in preclinical phase
• MFC-1040 for the treatment of idiopathic pulmonary fibrosis (IPF), currently in preclinical phase
• MFC-next, which consists of identifying new anti-MIF small molecules for the treatment of multiple sclerosis (MS), rheumatoid arthritis (RA), and other high-value indications in the field of chronic inflammation, currently in discovery phase

R&D STRATEGY

APaxen’s R&D is focused on research and development of breakthrough therapeutics for the treatment of diseases associated with chronic inflammation, with a primary focus in pulmonary arterial hypertension (PAH) and other deadly pulmonary diseases, including IPF and PH-IPF.

By the use of an integrated medicinal chemistry and molecular biology driven approach, Apaxen identifies and develops small molecule inhibitors of pleiotropic pro-inflammatory cytokine MIF.

Apaxen benefits from strategic collaborations with main academic research centers having translational expertise in pulmonary arterial hypertension (PAH).

MIF as a therapeutic target in PAH

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that plays a key role in several chronic inflammatory diseases (Drug Discovery Today 2019, 24, 428-439). It is produced by a variety of immune cells, including macrophages and lymphocytes, as well as endothelial and epithelial cells under certain conditions. MIF occupies an upstream position in the inflammatory cascade, higher than TNF-alpha and IL-6, and is associated with glucocorticoid resistance.

MIF and its cell surface receptor CD74 were found upregulated in patients with PAH, and are key players at the crossroad of inflammation, cancer-like phenotype and endothelial dysfunction in the pathogenesis of PAH. It has recently been demonstrated that overexpression of the MIF/CD74 axis induces pro-inflammatory phenotype of human pulmonary endothelial cells (P-ECs). Those P-ECs release specific adhesion molecules (i.e. ICAM-1, VCAM-1, and E-selectin), facilitating the adhesion and recruitment of inflammatory cells to the pulmonary vascular wall (Am. J. Respir. Crit. Care Med. 2015, 192, 983-997).

MFC-1040

Apaxen’s lead compound, MFC-1040, is a novel, first-in-class, orally bioavailable and selective small molecule inhibitor of pleiotropic pro-inflammatory cytokine MIF (macrophage migration inhibitory factor). MFC-1040 is believed to block MIF and prevent its binding to its cell surface receptor CD74, which inhibits production of pro-inflammatory mediators and vascular cell proliferation.

MFC-1040, which is being developed for the treatment of pulmonary arterial hypertension (PAH), has shown robust in vivo efficacy data in multiple rodent models of the disease (J. Med. Chem. 2018, 61, 2725-2736), namely monocrotaline (MCT), Sugen/chronic hypoxia (SuHx) and Bleomycine (BLM), both as monotherapy and/or as a combination with other PAH commercialized drugs. These in vivo preclinical models of pulmonary hypertension cover a large spectrum of the human PAH in terms of etiology and etiopathogeny. MFC-1040 has also shown efficacy in an animal model of idiopathic pulmonary fibrosis (Int. J. Mol. Sci. 2018, 19, 4105).

MFC-1040 has a unique mechanism of action (MoA) that combines potent anti-inflammatory, anti-fibrotic and anti-proliferative effects. It has the potential to revolutionize the standard of care of PAH, by halting or reverting the progression of the disease while available therapies only address the symptoms of this disease.

The non-clinical toxicity studies and CMC (Chemistry, Manufacturing and Controls) development for MFC-1040 are currently in progress. Apaxen expects to start first-in-human (FIH) clinical trials for MFC-1040 at end of 2021.

Read more about MFC-1040 in vivo efficacy

MFC-1040 in vivo efficacy in pulmonary hypertension

MFC-1040 has been shown to reverse pulmonary hypertension by improving hemodynamic, structural, histological and inflammatory endpoints without affecting body weight and cardiac frequency (J. Med. Chem. 2018, 61, 2725-2736). MFC-1040 treatment in rodent performed in a curative approach leads to:

Decrease in mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR), and increase in cardiac output (CO)
Decrease in right ventricular hypertrophy (RVH)
Reduction in pulmonary arterial wall thickness and right ventricular fibrosis (RVF)
Decrease in circulating level of key inflammatory mediators IL-6 and MCP-1 (CCL2), which are known to contribute to PAH

MFC-1040 in vivo efficacy in pulmonary fibrosis

MFC-1040 has also showed efficacy against pulmonary fibrosis in the well-established prophylactic bleomycin (BLM) mouse model of IPF (Int. J. Mol. Sci. 2018, 19, 4105).

MFC-1040 was shown to:

Decrease collagen content in lungs of mice
Normalize level of macrophage infiltration in the lungs of mice as well as serum level of inflammatory marker MCP-1 (CCL2)
Improve pulmonary hypertension secondary to pulmonary fibrosis

PARTNERSHIP

Apaxen has established strategic collaborations and partnerships with main academic research centers specialized in pulmonary arterial hypertension (PAH). We are looking for additional partnership opportunities regarding our preclinical programs in the field of chronic inflammation.

If you are interested in exploring partnership opportunities with Apaxen, please contact us at bart.wuurman@apaxen.com

INVESTORS

On July 2019, Apaxen has raised €3.3 million in a Series A equity funding round that gathered four funds: Theodorus, Sambrinvest, Innovation Fund, Financière Spin-off Luxembourgeoise along with members of “Be Angels”, one of the most important Business Angels network in Europe, while Theodorus was the lead investor.