Radiation-induced lung injury: Is there finally an approved treatment on the way?

TUCSON, Ariz.—Aqualung Therapeutics, an early-stage biotech company developing immune-focused therapeutic antibodies for patients suffering from acute and chronic disorders characterized by systemic inflammation, has been awarded a three year NIH Fast-Track Award (R42 HL152888-01) which will support mid- and late-stage development of a therapeutic to treat patients who undergo radiotherapy for treatment of lung and esophageal cancers and are at risk for developing radiation-induced lung injury (RILI).

The initial stage of this NIH STTR Award involves the final selection of the lead eNAMPT-neutralizing humanized therapeutic mAb between two candidates, ALT-100 and ALT-200; with selection utilizing in-vitro and preclinical in-vivo models of RILI. The second STTR stage supports completion of pharmacokinetic/ pharmacodynamic and toxicology studies with the lead mAb ALT-100/ALT-200 candidate in appropriate animal models and submission of an FDA IND application.

The development of RILI is a potentially fatal toxicity in cancer patients undergoing thoracic radiotherapy for lung or esophageal cancers, or in individuals exposed to ionizing radiation (IR) from a nuclear incident. Aqualung scientists identified nicotinamide phosphoribosyltransferase (NAMPT) as a novel upstream immune-based therapeutic target in the development of RILI and have generated a humanized monoclonal therapeutic antibody mAb, ALT-100, which is designed to suppress the systemic inflammatory cascades and prevent radiation pneumonitis and radiation-induced lung fibrosis.

“There are currently no FDA-approved therapies for patients who experience radiation-induced lung injury and we believe our preclinical evidence is compelling and supports the advancement of ALT-100/ALT-200 as a potential therapy for patients with thoracic cancer and potentially for individuals accidentally exposed in a nuclear incident. We are confident that ALT-100/ALT-200 will reduce the severity of potentially fatal radiation pneumonitis and radiation fibrosis. This aligns with our principle of finding cures for conditions of significant unmet medical needs that are driven by runaway inflammation,” stated Dr. Joe GN Garcia, CEO of Aqualung Therapeutics.

Pulmonary radiation injury manifests in approximately 8 percent of patients who receive thoracic radiation. However, reports of the incidence of symptomatic radiation pneumonitis ranges from 1-34 percent of patients who receive thoracic radiation for malignancy. Additionally, without FDA-approved therapies for this condition, it is also important to have a viable therapeutic available to treat patients who may be exposed to a nuclear incident as part of our national and global state of preparedness. The Aqualung team is prepared to execute and achieve all the milestones associated with this STTR grant.

“Unchecked inflammation is a major contributor to many disease states and at Aqualung, we believe eNAMPT plays a central role in promoting this inflammatory cascade. This STTR grant, the second large NIH-funded award supporting a focus on a mAb that neutralizes eNAMPT, provides Aqualung the needed financial resources to immediately validate our target therapeutic in additional models and then initiate all IND-enabling studies,” said Stan Miele, president and chief business officer of Aqualung Therapeutics. The grant allows Aqualung to initiate early clinical development with non-dilutive capital.