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AMB-053 for IPF

Disease and Prevalence

IPF is a chronic progressive inflammatory and fibrotic interstitial lung disease of unknown (idiopathic) cause which carries a sobering 3-5 year median survival from diagnosis if untreated (1). Indeed, an estimated 50,000 people die from IPF in the U.S. each year, more deaths than from breast cancer. Common risk factors for IPF include:

  • Cigarette smoking: Approximately 75% of people with IPF are current or previous cigarette smokers.

  • Male gender: Approximately 75% of patients with IPF are male.

  • Age: Most patients with IPF are over the age of 50 years.

In IPF, the lung tissue becomes scarred and the thickened stiff tissue leads to shortness of breath and a dry cough. Additional symptoms include fatigue, weight loss, aching muscles and joints and swelling of fingers and legs and toes. There’s no cure for IPF, but treatments can slow the lung damage and some patients receive lung transplants.

IPF affects close to 300,000 people in the US and the European Union and approximately 3 million worldwide (2).

Pathogenesis and AMB-053 Mechanism of Action

The etiology of IPF is not fully understood, but a current paradigm is that acute lung injury and early inflammatory responses, including macrophage activation, followed by persistent injury, leads to aberrant macrophage differentiation, wound healing responses, and pulmonary fibrosis (3). Certain types of macrophages, sometimes referred to a M2 macrophages, are thought to play a key role in the excessive fibrogenesis and development of IPF. Importantly, CSF1 acting at the CSF1R appears to play an important role in this pro-fibrotic macrophage response in IPF (4)

Figure 1. A schematic for the role of CSF1 & M2 Macrophages in IPF

Current Treatment & Unmet Need

Two drugs, pirfenidone and nintedanib, are approved by the European Medicines Agency and the US Food and Drug Administration for the treatment of IPF. However, both provide only limited efficacy and are associated with an unfavorable side effect profile (5). IPF patients are in clear need of therapeutics with much better efficacy and safety profile. In addition, the complex etiology necessitates combination therapy, hence drugs with novel mechanism of action are much needed.

AMB-053 Differentiation

With a novel yet preclinically-validated mechanism of action and demonstrated clinical safety, tolerability, and activity (6), AMB-053 represents a first-in-class therapeutic option as either a monotherapy or combination therapy for IPF.

References

  1. Raghu G et al., Am. J. Respir. Crit. Care Med. 2011; 183:788

  2. Global Data 2020.

  3. Zhang L et al., Resp. Research 2018; 19:170

  4. Hou J et al., Cell Communication Signal 2018; 16:89

  5. Maher T et al., BMC Pulmonary Med. 2017; 17:124

  6. Papadopoulos KP et al., Clin. Cancer Res. 2017; 23:5703

AMB-053 is a human monoclonal antibody targeting CSF1R that is thought to play a critical role in idiopathic pulmonary fibrosis (IPF) pathogenesis.

Delivered via a proprietary technology, AMB-053 is mechanistically and clinically well-positioned as a first-in-class therapeutic for the treatment of IPF either as a monotherapy or in combination with other agents.

 

Pharmaceutical

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