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

Joel Crouzet
PhD – Chief Executive Officer

Dr Crouzet has 35 years of experience of R&D in the Pharma and biotech (including executive positions in 4 different start-up). Dr Crouzet has been involved actively in 5 therapeutic projects that went up to the clinic, in various therapeutic areas. He recently co-founded InnaVirVax a French based company, and as Chief Executive Officer for 8 years allowed the company to develop from the bench an innovative drug candidate for HIV infections. Dr Crouzet is a molecular biologist by training but has worked in many different fields, including oncology, cardiovascular diseases, infectious diseases, immune -related diseases, hepatology etc. Dr Crouzet is the co-inventor of more than 30 patent families, two of which are used industrially for the manufacture of vitamin B12, and more than 60 peer reviewed publications.

Gael Jalce
Founder
PhD – Chief Scientific Officer

Dr Jalce has founded Apaxen in 2018 and serves as Chief Scientific Officer and Board Observer member. He is currently heading the medicinal chemistry research and non-clinical product development at Apaxen.
Dr Jalce has over 12 years’ experience in biotechnology industry in fields such as drug discovery, preclinical development including CMC (Chemistry, Manufacturing and Controls), and business development. From 2013 to 2018, Dr Jalce was the Founder, Chief Executive Officer and Chief Scientific Officer of Mifcare, a French biotechnology startup company that was specialized in the discovery and development of inhibitors of cytokine MIF for the treatment of chronic inflammatory diseases. Under its leadership, Mifcare has set up strategic R&D collaborations with academic partners and preclinical CROs which led to the identification of anti-MIF lead candidate MFC-1040 and several backup analogues. Dr Jalce holds a PhD in Organic Chemistry from Paris-Sud University, Paris-Saclay University, and has completed a postdoctoral training in the Department of Chemistry and Biochemistry at the Florida State University. Dr Jalce has a business training from HEC Paris Business School, Challenge Plus.

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 contact@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.