Generation Bio’s stock plummeted 54% to $6.35 yesterday after it reported in an SEC filing that its hemophilia A therapy data in mice couldn’t be duplicated in non-human primate studies.
Generation Bio’s stock plummeted 54% to $6.35 yesterday after the company reported in an SEC filing that its hemophilia A therapy data in mice couldn’t be duplicated in non-human primate studies.
In mouse models, the company’s experimental gene therapy demonstrated peak mean human factor VIII expression of 205% of normal. In hemophilia A, factor VIII is a protein essential for blood clotting and is a key biomarker for the disease. Gene therapies, such as Generation Bio’s, are attempting to fix the protein deficiency in order to prevent episodes of bleeding.
But, once they tested their therapy in non-human primates, the peak means human factor VIII expression dropped dramatically to only 2%.
The company closed on an initial public offering (IPO) in June 2020, when stocks were trading for $19 per share. They raised about $230 million in the IPO. This is an example of the risk and volatility of investing in biotech companies with only preclinical data.
The company’s therapy is a closed-ended DNA (cdDNA) delivered through a novel, cell-targeted lipid nanoparticle (ctLNP). In July 2021, Generation Bio reported plans to incorporate its novel, proprietary rapid enzymatic synthesis (RES) for cdDNA production into its pipeline programs, improving cdDNA purity to 99%.
Conventional gene therapies utilize viruses, typically adeno-associated viruses (AAV), as vectors to transport their gene therapy product. Generation Bio is attempting to use a minuscule fat particle, much like how the COVID-19 mRNA vaccines by Moderna and Pfizer-BioNTech deliver their payloads. One limitation of gene therapies is that some patients have immune responses to the viruses used as vectors, or if the therapy’s effectiveness wanes and another dose is required, the immune system reacts adversely to it.
“Over the course of the year, we have made significant progress in the development of our platform,” said Matthew Stanton, chief scientific officer of Generation Bio. “We have demonstrated that RES produces highly pure ceDNA across a variety of manufacturing scales and we have developed new production processes that have similarly enabled substantial improvements in the control and consistency of our ctLNPs.”
He went on to say, “We are working to translate the improved potency and decreased variability that we have observed in mice to NHPs. By applying novel analytical methods to these preclinical studies in both species, we have gained important insights that we believe will allow us to advance additional novel proprietary ctLNPs to meet our target profile for a hemophilia A development candidate.”
Geoff McConough, Generation Bio’s chief executive officer, stated, “At Generation Bio, we are innovating genetic medicines intended to exceed the limits of conventional gene therapies and to impact the lives of millions of people. Since our founding, we have been leading the frontier of systemic DNA delivery to build an entirely new non-viral genetic medicine platform to realize this vision. While we still have work to do, we believe the creativity and rigor of our science will unlock the full potential of genetic medicine. We have a terrific team and strong balance sheet to pursue this work and look forward to further progress in the next year.”
The company’s original timeline had them picking clinical candidates during 2020, with IND-enabling studies run this year and submitting to regulators for clinical trials sometime in 2022. Now, clearly, that timetable is worthless, and the company says it will be announcing its schedule in the future.
