Moleculin Biotech, Inc. · NASDAQ:MBRX
Moleculin Biotech — Corporate Update (April 2020)
16 slides from Moleculin Biotech's corporate update, Apr 17, 2020
Slide 1: Investor Conference Call to Discuss the COVID-19 Potential for WP1122
Developing ground-breaking therapies for highly challenging diseases April 16, 2020 Investor Conference Call to Discuss the COVID-19 Potential for our Drug Candidate WP1122 (Nasdaq: MBRX)
Slide 2: Disclaimer
Disclaimer All statements contained herein other than statements of historical fact, including statements regarding our future results of operations and financial position, our business strategy and plans, and our objectives for future operations, are forward-looking statements. The words “believe,”
Slide 3: WP1122 COVID-19 Opportunity
WP1122 COVID-19 Opportunity • Viruses depend on glycolysis and glycosylation for infectivity and replication • Glycolysis and glycosylation can be disrupted by using a glucose decoy known as 2-DG • While 2-DG has been shown to be effective in vitro, its lack of drug-like properties makes it ineffect
Slide 4: Viruses are Highly Dependent on Glucose
Viruses are Highly Dependent on Glucose Glycan Glycoprotein 2 Different Processes Glucose provides energy in the form of adenosine tri-phosphate (ATP) to viral host cells via glycolysis, as well as enabling glycan formation supporting creation of glycoproteins during glycosylation. 4
Slide 5: Glucose Plays a Critical Role in Glycosylation
Glucose Plays a Critical Role in Glycosylation Enveloped viruses depend on glycosylation, which begins by hijacking the host cell secretory pathway, where combinations of sugar molecules (including glucose and mannose) called “glycans” are combined with proteins, as “folding” provides 3- dimensional
Slide 6: Viruses Upregulate Host Cell's Glycolysis
Viruses Upregulate Host Cell’s Glycolysis Viruses induce an anabolic state in host cells, which in turn makes them highly dependent upon glycolysis for adequate energy production – Gualdoni G. et al. Rhinovirus induces an anabolic reprogramming in host cell metabolism essential for viral replication
Slide 7: 2-DG is a Glucose Decoy
2-DG is a Glucose Decoy 2-DG appears to the body to be natural glucose, but its lack of one hydroxyl group (shown in red on D- (2-DG) Glucose above) means that 2-DG will not convert into energy via glycolysis and it will not form the proper building-blocks for glycan formation during glycosylation.
Slide 8: 2-DG Disrupts Both Glycosylation and Glycolysis
2-DG Disrupts Both Glycosylation and Glycolysis Both Processes Disrupted The inhibition by 2-DG of glycosylation and glycolysis are both believed to play a role in limiting viral infectivity and replication. 8
Slide 9: 2-DG Has Well-Documented Anti-Viral Properties
2-DG Has Well-Documented Anti-Viral Properties • Gualdoni G. et al. Rhinovirus induces an anabolic reprogramming in host cell metabolism essential for viral replication. PNAS. 2018, • Rhinovirus E7158–E7165, vol. 115, no. 30 • Schmidt M. et al. Interference of Nucleoside Diphosphate • Herpesvirus De
Slide 10: 2-DG Inhibition Now Demonstrated in SARS-CoV-2
2-DG Inhibition Now Demonstrated in SARS-CoV-2 2-DG completely stops replication of SARS-CoV-2 in vitro in human Caco-2 cells. Based on research conducted at The Institute of Biochemistry at Goethe Effect of in vitro incubation of non- University Frankfurt reported in an unreviewed article recently
Slide 11: 2-DG Is Considered Safe and Well-Tolerated in Humans
2-DG Is Considered Safe and Well-Tolerated in Humans • Raez L.E., et al. “A phase I dose-escalation trial of 2-deoxy-D-glucose alone • Tested in over 100 patients in multiple or combined with docetaxel in patients with advanced solid tumors.” Cancer Chemother Pharmacol. 2013 Feb;71(2):523-30. doi: 1
Slide 12: Unfortunately, 2-DG Lacks Drug-Like Properties
Unfortunately, 2-DG Lacks Drug-Like Properties 2-DG’s lack of drug-like properties limits its in vivo performance. Short half-life, Rapidly metabolized, Poor tissue/organ uptake and retention 2-DG We believe 2-DG’s performance in humans is limited by its lack of drug-like properties. Because it is r
Slide 13: WP1122 is a Prodrug of 2-DG
WP1122 is a Prodrug of 2-DG 6 5 WP1122 4 1 metabolizes 3 2 to 2-DG (2-DG) The presence of two acetyl groups (in blue) in WP1122 forms esters with hydroxyl groups at positions C-3 and C-6 and greatly enhances its tissue/organ uptake and retention. 13
Slide 14: WP1122 Significantly Outperforms 2-DG in animal models
WP1122 Significantly Outperforms 2-DG in animal models 2-DG Generated from WP1122 10x 10x Up Up To To 2.6x 2-DG 1.8x Half-Life Plasma Organ Uptake Tumor Concentration Potency Zielinski R, et al. “Preclinical evaluation of WP1122, a 2-DG prodrug and inhibitor of glycolysis.” Proceedings: Symposia on
Slide 15: Summary
Summary • Viruses depend on glycolysis and glycosylation for infectivity and replication • Glycolysis and glycosylation can be disrupted by using a glucose decoy known as 2-DG • While 2-DG has been shown to be effective in vitro, its lack of drug-like properties makes it ineffective as a drug in hum
Slide 16: Investor Conference Call to Discuss the COVID-19 Potential for WP1122
Developing ground-breaking therapies for highly challenging diseases April 16, 2020 Investor Conference Call to Discuss the COVID-19 Potential for our Drug Candidate WP1122 (Nasdaq: MBRX)