Candidate: APN01

Type: Recombinant human angiotensin-converting enzyme 2 (rhACE2) developed to treat acute lung injury, acute respiratory distress syndrome, and pulmonary arterial hypertension.

APN01 is designed to imitate the human enzyme ACE2 so that the virus can no longer infect the cells, as SARS-CoV-2 binds to soluble ACE2/APN01 instead of ACE2 on the cell surface. APN01 is also designed to reduce harmful inflammatory reactions in the lungs and protects against acute lung injury/acute respiratory distress syndrome (ALI/ARDS).

2021 Status: Selected for ACTIV-4d Trial—APN01 will be one of at least three drug candidates to be evaluated in the NIH’s ACTIV (Accelerating COVID-19 Therapeutic Interventions and Vaccines) 4d RAAS trial, the Vanderbilt Institute for Clinical and Translational Research (VICTR) said May 6.

VICTR has been awarded a $60 million grant to lead the ACTIV-4d RAAS trial, which is designed to evaluate treatments targeting the RAAS and to determine whether modulation of the RAAS is an effective strategy for preventing progression to critical illness, multiorgan failure, or mortality in hospitalized COVID-19 patients.

ACTIV-4d RAAS is expected to enroll approximately 1,600 patients at more than 50 sites, including members of the Prevention and Early Treatment of Acute Lung Injury (PETAL) Network, supported by the NIH’s National Heart, Lung, and Blood Institute. In addition to APN01, ACTIV-4d RAAS is also expected to evaluate Constant Therapeutics’ TXA127, and Trevena’s TRV027.

Clinical Benefit Cited—APEIRON said March 12 that APN01 showed statistically significant improvements in specific areas for severely ill COVID-19 patients in a Phase II trial (NCT04335136). A reduction in viral RNA load over time was seen in the APN01 treatment group. Viral RNA levels over time compared to baseline showed a statistically significant improvement with APN01 treatment on day 3 and 5 compared to placebo. Also shown, according to the company, was a statistically significant improvement in mechanical ventilator-free days in alive patients and reduction in viral load in the group treated with APN01 compared to placebo. APN01 also demonstrated a positive impact on key biomarkers of the renin angiotensin system (RAS), demonstrating in vivo efficacy of the drug, APEIRON added.

The data also showed that nine patients treated with APN01 died or received invasive ventilation compared to 12 patients treated with placebo—though APEIRON acknowledged that statistical significance was not achieved due to the low total number of events. The company added that standard of care had improved dramatically since study initiation, resulting in fewer deaths and less use of nvasive mechanical ventilation than at the time of design of the study.

The multi-center, double-blind, randomized, placebo-controlled, interventional Phase II trial assessed the safety, tolerability and efficacy of APN01 in 178 patients with severe COVID-19 compared to placebo. Both the APN01 treatment arm (88 participants) and the placebo arm (90 participants) also additionally received standard of care (SOC). Patients received treatment for 7 days with follow-ups until day 28.

2020 Status: APEIRON said June 3 it had launched a Phase II clinical trial of APN01 to treat COVID-19 (NCT04335136) in Austria, Denmark, Germany, and the U.K, with plans to expand the study into the U.S. and Russia. The trial aims to compare APN01 to placebo in up to 200 severely infected COVID-19 patients at 10 sites. APEIRON received regulatory approvals for the trial in Austria, Germany, and Denmark in April.

Also in June, APEIRON completed a financing round totaling €17.5 million ($20.2 million), toward further development of APN01 for the treatment of seriously ill COVID-19 patients, as well as the further development of immuno-oncology projects. The financing consisted of €5.6 million ($6.5 million) in public funding and guarantees from the Austrian Research Agency (FFG), the Vienna Business Agency (WAW), the Austria Economic Service Company (AWS) and Erste Bank—and €11.9 million ($13.7 million) raised as part of a rights issue with a private placement from existing and new private and institutional investors, including the Vienna Insurance Group (VIG).

VIG will receive a 3.26% stake in APEIRON following an investment of approximately €7 million ($8.1 million) in the company.

APN01 has been shown to be safe and well-tolerated in a total of 89 healthy volunteers and patients with pulmonary arterial hypertension (PAH) and ALI/ARDS in previously completed Phase I and Phase II clinical trials, APEIRON said.

In March, The First Affiliated Hospital of Guangzhou Medical University disclosed on ClincalTrials.gov that a planned open label, randomized, controlled, pilot clinical study of APN01 in patients with severe SARS-CoV-2 infection had been withdrawn without Chinese Center for Drug Evaluation (CDE) approval. No explanation has been given on the company’s website or on ClinicalTrials.gov. The trial was designed to obtain preliminary biologic, physiologic, and clinical data in patients with COVID-19 treated with rhACE2 or control patients, to help determine whether a subsequent Phase IIb trial is warranted.

Suzhou-based Angalpharma coordinated the Chinese clinical trial, with support from dMed Pharmaceutical, a CRO based in Shanghai.


COVID-19: 300 Candidates and Counting

To navigate through the >300 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:

FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.

DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data

KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.

TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.

GEN has also tagged the most common treatment types:

● ANTIVIRAL
● VAX
● ANTIBODY
● RNA