ALVR106: An investigational allogeneic, off-the-shelf, multi-virus specific T cell (VST) therapy targeting respiratory viruses
Respiratory Virus Infections in high-risk patients with T cell deficiencies
Acute respiratory tract infections are a major public health concern. High-risk patients with T cell deficiencies, including hematopoietic stem cell transplant (HCT) and solid organ transplant (SOT) recipients, individuals older than 65 and younger than five years old, as well as other individuals whose immune systems are suppressed, face a range of serious consequences when faced with these common respiratory infections, including: pneumonia, hospitalizations, respiratory failure, and death.
ALVR106 has the potential to transform the treatment of respiratory viruses and substantially reduce the severity of viral respiratory infections while improving patient outcomes.
Acute respiratory tract infections due to community-acquired respiratory viruses such as RSV, Influenza, PIV, and hMPV are a major public health concern. A Phase 1/2 study evaluating the safety and antiviral activity of ALVR106 in post-transplant patients with respiratory viral infections is ongoing. (ClinicalTrials.gov: NCT04933968).
Upper and Lower Respiratory Tract Infections in HCT Recipients
Respiratory tract infections due to influenza, RSV, PIV, and hMPV are found in up to 40 percent of allogeneic HCT recipients. For approximately half of these HCT patients, these viral infections progress from less serious upper tract respiratory infections, with symptoms similar to those of a common cold, to far more serious lower respiratory tract infections with severe symptoms including pneumonia and bronchiolitis and are associated with increased mortality up to 20-45%.
Community-acquired respiratory viral infections involving hMPV, influenza, PIV and RSV have been attributed to mortality caused by progression to lower respiratory tract infection (LRTI), such as pneumonia and bronchiolitis in immunocompromised HCT and SOT patients, and bronchiolitis obliterans syndrome (BOS) or chronic lung allograft dysfunction (CLAD) in lung transplant recipients. With changes in transplant practices, the severity of these viral infections is increasing and the timeframe when patients are subjected to potentially fatal infections has expanded. Mortality from these infections can be as high as 23% to 50% for HCT patients with pneumonitis. In SOT, especially lung transplant recipients, mortality rates due to progression to LRTI are as high as 20%.
There are limited or no treatment options available for these respiratory viruses.
Pre-Clinical Data and Development Plan
In vitro data demonstrate that ALVR106 reactive cells have antiviral activity against each of the targeted viruses with minimal or no activity against non-virus-infected cells. These preclinical data, published in Haematologica in 2019, support the potential for antiviral benefit and safety of ALVR106 when administered to patients.
A Phase 1/2, double-blind, placebo-controlled, dose escalation and expansion trial of ALVR106 in addition to standard of care is ongoing.