Aridis Pharmaceuticals, Inc (NASDAQ: ARDS) announced the enrollment of its first COVID-19 patient in an ongoing Phase III clinical trial of its investigational AR-301, a monoclonal antibody against S. aureus induced pneumonia in patients who were already on mechanical ventilators. These patients can be at risk to dangerous ‘superinfections” as is the case with this patient.
What is a core problem Aridis Pharmaceuticals is addressing?
S. aureus is the bacterium commonly responsible for all major bone and joint infections. This manifests in one of three forms, including 1) osteomyelitis, 2) septic arthritis, and 3) infection from a replacement joint surgery.
S. aureus represents a leading cause of hospital-acquired lower respiratory tract infections (e.g. pneumonia), bloodstream, skin, soft tissue and surgical site infections. Treatment of these infections has become more challenging due to the emergence of multi-drug resistant (MRSA) strains. Resistance to beta-lactam antibiotics in MRSA strains is a major problem in hospital and healthcare settings in in developed countries around the world—from the U.S. and UK to Japan.
For example, the incidence rate of all invasive MRSA infections, including those outside of hospitals, is high compared with other bacterial pathogens, with these infections resulting in mortality rates of up to 50%.
How does this apply to COVID-19 patients?
Patients infected with severe cases of SARS-CoV-2, the virus behind the COVID-19 pandemic, often require prolonged mechanical ventilation in the intensive care unit (ICU)—they are at risk: prone to secondary infections known as ‘superinfections’ by opportunistic pathogens such as bacteria. Superinfection is a reported complication in COVID-19 patients, which exacerbates morbidity and rate of mortality.
Who is Aridis Pharmaceuticals Inc.?
They are a biopharmaceutical company focused on the discovery and development of novel anti-infective therapies to treat life-threatening bacterial infections. Based in San Jose, CA (Silicon Valley), they were founded nearly two decades ago in 2003 by Eric Patzer and Vu L. Truong. Both founders worked at Aviron, which was a vaccine developer based in the Bay Area. In 2001, MedImmune (now AstraZeneca) acquired Aviron for $1.5 billion—its primary asset with FluMist, a promising influenza treatment.
The company discovers and develops anti-infectives to be used as add-on treatments to standard-of-care antibiotics. The Company is utilizing its proprietary APEX™ and MabIgX® technology platforms to rapidly identify rare, potent antibody-producing B-cells from patients who have successfully overcome an infection, and to manufacture mAbs for therapeutic treatment of critical infections. These mAbs are already of human origin and functionally optimized for high potency by the donor’s immune system; hence, they do not require genetic engineering or further optimization to achieve full functionality.
What is AR-301?
With a tradename Salvecin® AR-301 is a fully human monoclonal igG1 antibody (mAb) that specifically targets S. aureus alpha-toxin, an important virulence factor that is secreted by both methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA). AR-301 protects against alpha-toxin mediated destruction of host cells, preserving human immune cells. The investigational product’s mode of action is independent of the antibiotic resistance profile of S. aureus and it is active against infections caused by both MRSA and MSSA.
Recent Clinical Trial Data for AR-301
The company reports on its website that recent clinical trial data from a double-blinded, placebo-controlled Phase IIa study conducted across 31 intensive care units in four European countries and America evaluating the safety, pharmacokinetics and efficacy of ascending doses of AR-301.
Additionally, the investigational product was tested as an adjunctive therapy to standard of care antibiotics in patients diagnosed with severe hospital-acquired pneumonia (HAP) and ventilator associated pneumonia (VAP) patients caused by S. aureus. The company reports that those patients treated with AR-301 consistently demonstrated less time spent under mechanical ventilation and higher rates of S. aureus eradication as compared to those patients given antibiotics only. The company reports in these cases AR-301 is deemed to be safe and well tolerated. AR-301 was offered Fast Track designation by the FDA and orphan drug designation in the European Union. It is now being evaluated in a global Phase III study, which is the context for the COVID-19 patient under treatment.
The Clinical Trial
A global, multicenter, prospective, randomized, double-blind, placebo-controlled, parallel design protocol-based Phase III study in patients with Ventilator-Associated Pneumonia (VAP) caused by S. aureus targets up to 240 patients. They are randomized 1-1 to be treated with placebo plus standard of care (SOC) or AR-301 (20mg/kg) plus SOC. These patients have a documented diagnosis of pneumonia due to S. aureus and require ICU care, who have been intubated or have a tracheostomy tube in place) and mechanically ventilated for at least 48 hours are eligible for screening. Study subjects receive a single treatment dose at Day 0 plus the SOC antibiotic treatment and thereafter enter a safety, efficacy and PK study period for a total study duration of 28 days. The selection of SOC antibiotics is made in accordance with local best practices at the discretion of the investigator. The company’s key contact for the study is Lynne M. Deans, MT.