AR-oo1
discovery
preclinical
phase 1
Severe Asthma
COPD
(Chronic Bronchitis)
IPF
(Orphan Disease)
NCFB
(Orphan Disease)
Lung Infections
PAH
(Orphan Disease)
Cystic Fibrosis
New Chemical
Entities

AR-001

AR-001, our lead product candidate is a best-in-class dry powder formulation of niclosamide optimized for self delivery using a capsule-based dry powder inhalation device. This proprietary drug-device combination product benefits from the established safety on niclosamide and the optimal target coverage that will be achieved by direct delivery to the airways. AR-001 is currently being tested in IND enabling in vivo studies to establish safety and determine optimal clinical dose ranges.
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Tier 1 Indications

Severe Asthma

(SA)
Our lead indication is severe asthma. We expect to demonstrate improvements in lung function and symptoms by relaxing tightened airways and reducing mucus, something that no existing asthma treatment adequately achieves. Moreover, by blocking viral infection and upstream inflammation we believe that AR-001 will reduce exacerbations and compete well against expensive biologics that require injection.

COPD

(Chronic Bronchitis)
COPD patients also suffer from poor breathing due to inflammation and airway narrowing and achieve benefit from bronchodilators. We expect AR-001 to improve breathing in COPD patients by blocking multiple smooth muscle contractiles and reducing bronchitis-associated mucus and inflammation that is poorly controlled with steroids resulting in disease persistence and worsening.

IPF

(Idiopathic Pulmonary Fibrosis)
Besides epithelial and smooth muscle cells, TMEM16 is expressed by lung fibroblasts and overexpressed in IPF lung tissue. TMEM16A gene knockdown or pharmacological inhibition ameliorates fibrosis in disease models. TMEM16A is upregulated by TGFb and is essential for myofibroblast differentiation and fibrotic signaling in pulmonary fibrosis. Therefore, there is a reason to believe IPF can be treated with the TMEM16A inhibitor, AR-001.

NCFB

(Non-CF Bronchiectasis)
NCFB is an orphan disease in which the bronchi become permanently dilated due to a vicious cycle of chronic pulmonary inflammation and complications from prior infections. The condition is marked by considerable mucus build up and a high unmet medical need. Approximately 500,000 people in the US have non-CF bronchiectasis.

AR-001

In addition to our primary disease indications, AR-001 holds promise to treat PAH, CF, and Lung Infections. These Tier 2 indications are discussed below, and the company will seek opportunities to generate supporting preclinical and/or clinical data as appropriate.

Tier 2 Indications

PAH

(Pulmonary Arterial Hypertension)
TMEM16A activity is elevated in smooth muscle cells (SMC) and arteries of patients with PAH. Overexpression of TMEM16A leads to increased SMC proliferation, enhanced contractility, and remodeling. Smooth muscle specific knock-out of TMEM16A decreases hypertensive response following vasoconstrictor treatment and the TMEM16A inhibitor niclosamide has been reported to be active in ameliorating disease in two rodent models of PAH.

CF

(Cystic Fibrosis)
Cystic fibrosis is a disease associated with pathologic accumulation of dehydrated mucus in the airways. AR-001 represents a novel approach to treat CF because of TMEM16's role in controlling the overproduction and release of mucus that obstructs airways and leads to persistent infections, and the fact that bronchodilators are known to improve the lung function of CF patients.

Lung Infections

(Viral – Bacterial)
Niclosamide is a potent inhibitor of SARS-CoV-2 and other respiratory viruses, including influenza, rhinovirus, and RSV, that can also block the devastating inflammatory complications of infections leading to lung damage. Niclosamide is also a broad-spectrum antibacterial that operates through a distinct mechanism of action to inhibit multidrug resistant bacteria and their exotoxins. Our shelf stable inhaled formulation is ideal for treating lung infections that evades resistance mechanisms.

Building a Respiratory Disease Pipeline

Our work to date has led to a patent protected therapy directed against a validated new target for respiratory disease. We are strategically positioned to advance quickly to clinical trials.

Our small molecule and deep target biology knowledge positions us uniquely for identifying follow-on new chemical entities with improved activity. Our intention is to be the leaders in the development of inhaled TMEM16 inhibitors.