Tiziana Life Sciences has developed a handheld inhaler that will allow the rapid delivery of TZLS-501, its drug to treat inflammation of the lung in COVID-19. “The technology, we think, provides immediate relief thanks to the delivery speed,” said chairman Gabriele Cerrone.
The company described the development of this novel technology is a step forward toward expediting development of TZLS-501, its fully human anti-interleukin-6 receptor (anti-IL6R) mAb for treatment of patients infected with COVID-19 (SARS-CoV-2).
Tiziana believes TZLS-501 (anti-IL6R) combined with this newly introduced inhalation technology may rapidly inhibit inflammation in lungs and in combination with intravenous administration may deplete circulating levels of IL-6 and potentially halt progression of COVID-19-mediated lung damage and death. The company hopes the technology could also be applicable for use with other FDA approved mAbs and drugs.
“Direct delivery of anti-IL-6R mAb to the lungs using a portable handheld inhaler or nebuliser is a rapid and immediate therapy for children and adults infected with COVID-19. Importantly, this treatment with our fully human anti-IL-6R mAb (TZLS-501) has the potential to be a long-term therapy to halt progression and reduce mortality in patients with COVID-19, as a portion of the population may not opt to utilise a vaccine,” said Cerrone.
Patients infected with COVID-19 are known to develop an uncontrolled immune response (“cytokine storm”), which results in excessisive production of pro-inflammatory cytokines and other proteins such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-a) and granulocyte-macrophage colony-stimulating factor (GM-CSF), which in turn causes severe damage to lung tissue resulting in respiratory failure and eventually death. Among these cytokines, IL-6 seems to be one of the major culprits underlying coronavirus-mediated respiratory failure. Early clinical studies conducted by doctors in China suggested that anti-IL6R mAbs may be used in clinical practice for treatment of COVID-19. Consequently, China’s National Health Commission has recommended the use of Roche’s blockbuster drug, Actemra® and Sanofi’s Kevzera® for treatment of patients infected with COVID-19.
Excessive production of IL-6 is regarded as a key driver of chronic inflammation and is believed to be associated with the severe lung damage commonly observed with COVID-19 infections and acute respiratory distress syndrome (ARDS).
The filing of a comprehensive provisional patent application covering treatment with our anti-IL-6R mAb, as well as prophylactic intervention with a vaccine candidate, designed from Spike (S) protein of COVID-19, is an important step in finding a solution to the current pandemic. We look forward to providing updates on the development of this product candidate and its introduction into clinical trials in a real-world setting,” said Chief Executive Office and Chief Scientific Officer Dr Kunwar Shailubhai.
TZLS-501, a fully human mAb, was acquired from Novimmune in 2017. The cytokine, IL-6, a major determinant in the priming of pathogenic T cells to produce an inflammatory response, binds to its receptor subunit IL-6Rα on the cell membrane. The receptor IL-6Rα can be shed as a soluble sIL6Rα, which binds to circulating IL-6 cytokine in the blood. The downstream signaling from which sIL-6R is implicated mediates pro-inflammatory effect underlying the inflammatory diseases such as rheumatoid arthritis (RA) and acute respiratory distress syndrome (ARDS). The company believes that the novel features of TZLS-501 consisting of its dual mechanism of action to inhibit signaling by the membrane-bound and soluble IL-6 receptor and the rapid depletion of circulating IL-6 cytokines, which is the major cause of lung damage, provides this mAb with distinct advantages for treatment of COVD-19.
Link to Press Release.