In genetic medicine, childbirth is the key. You want to make sure that the drug reaches its destination in the body and doesn’t cause any problems along the way. But before that, you want to make sure that the chosen delivery vehicle has enough room to carry everything it needs for the trip. ReCode Therapeutics is developing technology to improve the capacity and targeting of genetic drugs, and its first stops are the lungs.
ReCode has two programs on track for clinical trials and biotechnology has raised $ 80 million to advance these and other programs. Pfizer Ventures and EcoR1 co-led the Series B funding round announced Thursday.
Many genetic drugs available as well as some still in development use modified viruses for delivery. These viruses are very good at getting into a cell, but the body sees them as foreign, so the immune system creates antibodies against them. This means that the viral administration can only be used once in a patient. Viruses can also trigger dangerous side effects.
ReCode avoids the limitations of viruses by using lipid nanoparticles (LNP). These particles are made from cholesterol and lipids, a type of fat, so the body is familiar with them, said CEO David Lockhart. This familiarity reduces the risk of an immune response. In addition, since LNPs do not cause the immune system to produce antibodies, they can be re-dosed if necessary. Equally important, these particles can be engineered to reach specific tissues in the body.
“We’ve only scratched the surface,” Lockhart said. “We can do even more with targeted delivery to more cell types, tissue types, beyond the liver, lungs and spleen. “
LNPs have a preference for going to the liver. This is great for genetic drugs for liver disease, and companies like Alnylam Pharmaceuticals have used this preference and optimized it for therapies that reach liver cells. Genetic drugs use three or four lipids in their LNPs. ReCode adds a fifth. The company’s delivery technology comes from the lab of Professor Daniel Siegwart of the Southwestern Medical Center at the University of Texas, co-founder of the company. Lockhart said the addition of a fifth lipid changes the way LNP binds to proteins in the blood in a way that eliminates the liver as a target and allows delivery to other targets in the body. The technology is called selective organ targeting, or SORT. In addition to the ability to target, Lockhart said ReCode’s LNPs offer greater capacity than viruses as well as the ability to transport mixed payloads of gene cargo.
ReCode has two main programs which are preclinical. One concerns primary ciliary dyskinesia (PCD), a disease that causes dysfunction of the cilia, organelles that extend from cells. The other is cystic fibrosis (CF), a disease that causes fluid to build up in the lungs. Both have definite genetic causes, but PCD has no cure and although Vertex Pharmaceuticals has developed drugs that treat various genetic mutations, Lockhart noted that around 10% to 13% of patients with cystic fibrosis do not respond. to these therapies.
ReCode aims to treat PCD and CF by providing RNA and gene correction therapies. The first therapies developed by the company were inhaled drugs to be given to the epithelial cells that line the lungs. These therapies will not need to be targeted because inhaling gets the medicine where it needs to go. But Lockhart noted that for some lung disorders, administration to the endothelial cells that line the blood vessels is necessary. These drugs, such as the Cystic Fibrosis Genetic Correction Therapy ReCode is developing, will use SORT.
The new funding will be used to bring the PCD and CF programs closer to the clinic. Lockhart said preclinical research that supports an investigational new drug (IND) application will begin in the first half of next year, followed by an IND filing in the second half of the year. Part of the capital will be used to develop additional programs which are also for respiratory disorders with defined genetic causes.
There are other companies that are trying to get LNP beyond the liver. Georgia Tech spinout Guide Therapeutics technology selects LNPs that can be used to deliver RNA to cells throughout the body. Beam Therapeutics saw enough promise in the approach to commit $ 120 million to acquire the startup earlier this year.
While ReCode’s technology delivery capability has applications beyond the lung, the company does not intend to pursue all of them. Lockhart said ReCode will focus on respiratory disorders while exploring partnerships with other companies interested in applying the technology to diseases affecting other parts of the body. In the shorter term, ReCode will build its own manufacturing capabilities to support its clinical trials.
ReCode raised $ 80 million in Series A funding last year. The latest funding added new investors Sanofi Ventures, funds managed by Tekla Capital Management, Superstring Capital and NS Investment. Previous investors participating in the new round include OrbiMed, Vida Ventures, MPM Capital, Colt Ventures, Hunt Technology Ventures and Osage University Partners. Although Pfizer’s venture capital arm co-led the funding, Lockhart said the pharmaceutical giant only gets one seat on the board and has no internal leads for SORT.
“They are very excited about the technology,” he said. “They basically want a front row seat. We were very clear on the fact that there was no coupling of rights, no guarantee of access to the technology.
Photo by ReCode Therapeutics