APL-9 / Apellis - LARVOL DELTA

Pre-existing humoral immunity and complement pathway contribute to immunogenicity of adeno-associated virus (AAV) vector in human blood. (PubMed, Front Immunol) - "By using a compstatin-based C3 and C3b inhibitor, APL-9, we demonstrated that complement pathway inhibition lowered CD86 levels on APCs, AAV uptake, and cytokine/chemokine secretion in response to AAV. Together these results suggest that the pre-existing humoral immunity to AAV may contribute to trigger adverse immune responses observed in AAV-based gene therapy, and that blockade of complement pathway may warrant further investigation as a potential strategy for decreasing immunogenicity of AAV-based therapeutics."

Journal • Gene Therapies • Genetic Disorders • Immune Modulation • Inflammation • CD86

A Study of APL-9 in Adults With Mild to Moderate ARDS Due to COVID-19 (clinicaltrials.gov) - P1/2; N=65; Completed; Sponsor: Apellis Pharmaceuticals, Inc.; Recruiting ➔ Completed

Clinical • Trial completion • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

"Lmk if you need a translation @JacobPlieth but indeed a mistake in you APL-9 article and complement in covid chart, pls fix thx! H/t to @Lybsoo merci mec! Javais meme pas lu larticle 😂" (@InvestrClouseau)

Apellis Pharmaceuticals Reports Fourth Quarter and Full Year 2020 Financial Results (GlobeNewswire) - "Apellis expects to report top-line data from its Phase 1/2 clinical study of APL-9, a targeted C3 therapy designed for acute conditions, in patients with severe COVID-19 in the second quarter of 2021."

P1/2 data • Novel Coronavirus Disease

Apellis Provides Update on APL-9 for Severe COVID-19 (GlobeNewswire) - P1/2, N=66; NCT04402060; Sponsor: Apellis Pharmaceuticals, Inc.; "...the company will not pursue additional development of APL-9...for the treatment of severe COVID-19. The decision followed an interim review of mortality data from the Phase 1/2 study by an independent data monitoring committee (DMC), which found no meaningful reduction in the overall mortality rate in patients treated with APL-9 in combination with standard of care therapy compared to standard of care alone. No safety signals were observed by the DMC....No additional endpoints were analyzed as part of the interim review by the DMC. Enrollment is complete, and the study reached the last patient visit."

Discontinued • DSMB • P1/2 data • Trial status • Infectious Disease • Novel Coronavirus Disease

Apellis Announces New Data Demonstrating Correlation between Complement Activation and COVID-19 Severity (GlobeNewswire) - P=Obs, N=41; P1/2, N=66; NCT04402060; Sponsor: Apellis Pharmaceuticals, Inc.; "Observational study in 41 patients hospitalized with COVID-19 found that nearly all patients had elevated systemic levels of C3a, a marker for C3 activation; median C3a levels were 3.7 times the upper limit of normal; In a Phase 1/2 interventional study, preliminary open-label safety results in first six patients support advancement of APL-9....Based on the results, an independent data monitoring committee recommended continuing the investigation of APL-9 in this study. Apellis is currently enrolling an additional 60 patients with COVID-19 and respiratory failure..."

DSMB • Observational data • P1/2 data • Infectious Disease • Novel Coronavirus Disease

A Study of APL-9 in Adults With Mild to Moderate ARDS Due to COVID-19 (clinicaltrials.gov) - P1/2; N=66; Recruiting; Sponsor: Apellis Pharmaceuticals, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Apellis Initiates Phase 1/2 Study of APL-9 in Patients with Severe COVID-19 (GlobeNewswire, Apellis Pharmaceuticals, Inc.) - "Apellis Pharmaceuticals....today announced that the company has initiated a Phase 1/2 clinical study of APL-9...in COVID-19 patients with respiratory failure including acute respiratory distress syndrome (ARDS)....Apellis initiated the Phase 1/2 study following preliminary results from its ongoing, non-interventional study in patients with ARDS secondary to COVID-19, which showed a substantial increase in the activation of the complement cascade....Apellis initiated the study upon clearance by the U.S. Food and Drug Administration, which expedited the review of the investigational new drug application for APL-9 in COVID-19."

Clinical data • Trial initiation date • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Study of APL-9 in Adults With Mild to Moderate ARDS Due to COVID-19 (clinicaltrials.gov) - P1/2; N=66; Not yet recruiting; Sponsor: Apellis Pharmaceuticals, Inc.

Clinical • New P1/2 trial • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Development of a Bioconjugate Platform for Modifying the Immune Response of Autoreactive Cytotoxic T Lymphocytes Involved in Type 1 Diabetes. (PubMed, Bioconjug Chem) - "Diabetic NOD splenocytes pretreated with APL9 bioconjugate were also not able to transfer diabetes into prediabetic NOD recipient mice. This work is beneficial to prevent T1D as an immunotherapy strategy to render autoreactive immune cells more tolerant of beta cells."

Journal

AUTOMATIC RECOGNITION OF DIFFERENT TYPES OF ACUTE LEUKAEMIAS IN PERIPHERAL BLOOD BY IMAGE ANALYSIS (ISLH 2019) - "...The goal of this work is the development of an extended machine-learning approach for the automatic recognition of different types of acute leukaemia. We analysed 442 PB smears from 206 patients: 86 healthy individuals, 53 with infections and 67 with acute leukaemia from the following origins: myeloid (AML:18), lymphoid (ALL-B:23), monocytic (AMONL:17) and promyelocytic (APL:9)... The key contribution of this work is a system able not only to detect blast cells, but also to recognize the lineage origin of blast cells. From a diagnosis perspective, it is relevant since it automatically allows to distinguish among different types of acute leukaemia."