Moleculin advances plan to strip and starve COVID-19

Moleculin Biotech is set to test its glucose decoy prodrug WP1122 as a treatment for the coronavirus. The plan is underpinned by evidence the drug may starve infected cells of energy while also exposing the COVID-19 virus to immune attacks.

Houston-based Moleculin originally identified WP1122 as a potential treatment for pancreatic cancer and glioblastoma multiforme. The plan going into 2020 was to wrap up formulation work in the first half the year and aim to file to run a clinical trial in 2021. Then the COVID-19 outbreak began, leading Moleculin to spy a new use for WP1122.

The plan to reposition WP1122 as a treatment for the novel coronavirus SARS-CoV-2 is underpinned by research into the effect of 2-deoxy-D-glucose (2-DG) on viruses. Those studies suggest the glucose decoy may curb viruses by depriving infected cells of glucose and stripping the pathogen of a method for hiding its presence from the immune system.

2-DG, not WP1122, was used in those studies. Yet, as a prodrug of 2-DG, WP1122 may be able to deliver the efficacy hinted at by the early-stage research in a package better suited to use in people. 

“Although 2-DG has shown promise in the laboratory in relevant in vivo models, its potential as a therapy is severely limited by its lack of drug-like properties, including circulation time and organ uptake. Our drug candidate … appears to overcome 2-DG's lack of drug-like properties and is able to significantly increase tissue/organ concentration,” Moleculin CEO Walter Klemp said in a statement.

The evidence supporting the use of WP1122 against the coronavirus is early stage. Moleculin only has preclinical data to support its belief that WP1122 has better drug-like properties than 2-DG, and the case for using 2-DG against viruses other than SARS-CoV-2 is based on studies in tissue cultures and other preclinical tools. 

Moleculin is working with the University of Texas Medical Branch (UTMB) to learn whether the early signs of promise will translate into a candidate worth testing in the clinic. The deal tasks Moleculin with supplying WP1122 and related molecules to UTMB for testing against models of viral diseases including COVID-19. UTMB’s tests will build on earlier work at the university showing glucose decoys slow the spread of other viruses.

With Moleculin mainly focused on cancer, the potential of WP1122 to work better than the glucose decoys tested by UTMB may have gone unexplored. However, as has happened at other biotechs, the coronavirus drove Moleculin to rethink its priorities.  

“All of the sudden the stakes are higher. We were moving at one speed when we thought this was secondary to our cancer treatment agenda. But once coronavirus hit the scene and we thought we had the ability to impact that, it moved up the priority list,” Kemp told the Houston Chronicle.