A rare form of Duchenne muscular dystrophy is treated with a gene drug that causes skeletal muscle cells to produce a key protein they lack. Although these therapies slow the progression of the disease that deprives patients of their ability to walk, patients often die from Duchenne’s effects on the heart and breathing. Biotech company PepGen is developing a drug that can deliver its therapeutic payload not only to skeletal muscle, but also to the diaphragm, cardiac muscle and central nervous system. Scientists at PepGen believe this broader delivery capability gives it an advantage, and the clinical-stage company has joined the public market as it begins to prove its approach.
Cambridge, Mass.-based PepGen originally planned to issue 7.2 million shares priced between $13 and $15 a share, which would have raised $108 at the midpoint of $14 a share. The company was able to raise that amount, but it would have to offer more shares to do so. Late Thursday, PepGen Pricing It issued 9 million shares at $12 per share. The shares began trading on the Nasdaq on Friday under the ticker “PEPG.”
For diseases with known genetic causes, one treatment is antisense oligonucleotides, which are therapies made from small pieces of synthetic DNA or RNA. The four FDA-approved Duchenne treatments—Three from Sarepta Therapeutics and One from NS Pharma– are all antisense oligonucleotides. PepGen in its IPO application The limiting factor for oligonucleotide-based drugs is delivery.
“By itself, oligonucleotide therapy is not easily distributed to heart and skeletal muscle, key tissues affected by neuromuscular disease, and cannot be efficiently absorbed into these cells,” the company said. “To address this challenge, we engineered our proprietary EDO technology to optimize tissue penetration, cellular uptake, and nuclear delivery, which we believe may enhance the therapeutic activity of oligonucleotides and improve tolerance of these genetic medicines sex.”
EDO stands for Enhanced Delivery Oligonucleotide. The technology platform designs peptides so that they can better deliver oligonucleotide cargoes to desired tissue destinations. In preclinical studies, PepGen has demonstrated its technology to deliver oligonucleotides into tissue types including smooth, skeletal and cardiac muscle, and the central nervous system.
PepGen’s lead project, called PGN-EDO51, is designed to treat Duchenne patients, whose disease can be solved by having the cell’s protein-making machinery skip exon 51, the segment of the gene that contains the code that is translated into protein one. This approach results in shortened versions of key muscle proteins that Duchenne patients lack.
Exon skipping is the same approach used by Sarepta’s first FDA-approved Duchenne therapy, Exondys 51. Sarepta is developing next-generation exon 51 skipping drugs that use cell-penetrating peptides to improve delivery. PepGen said in its IPO filing that it conducted a monkey study comparing its experimental drug to a molecule equivalent to Sarepta’s next-generation exon captain. According to PepGen, the results showed a >70% increase in exon 51 skipping in skeletal muscle, including the diaphragm. PepGen therapy also showed greater activity.
Last month, PepGen began a Phase 1 single-ascending-dose study recruiting healthy volunteers in Canada. Preliminary data from the clinical trial is expected to be released by the end of the year. The EDO platform resulted in a second program, PGN-EDODM1, which the biotech is developing as a treatment for myotonic dystrophy type 1 (DM1), a rare muscle disease for which there is currently no FDA-approved treatment . PepGen said in its prospectus that it expects to submit an investigational new drug application for the DM1 therapy in the first half of next year.
A second Duchenne therapy, PGN-ENDO53, is being developed to address patients who can be treated by skipping exon 53. PepGen said it expects to begin testing the drug in monkeys in the second half of 2022. In addition to further Duchenne research, PepGen said it plans to investigate potential applications of its technology in other indications, including neuromuscular and neurological disorders.
The science behind the PepGen drug is based on more than a decade of research in the labs of Matthew Wood, professor of neuroscience at Oxford University, and Mike Gait, honorary scientist at the UK Research Council for Research and Innovation in Medicine. PepGen was founded in 2018; in 2020, the biotech company closed a $45 million Series A round. Before the IPO, PepGen had raised $163.9 million, the company said in its prospectus.Its most recent financing is $112.5M crossover round It closed last August.
According to the prospectus, RA Capital is PepGen’s largest shareholder, holding a 23.7% stake after the IPO. Oxford Sciences Enterprises, a company that holds shares in Oxford University’s scientific branch, owns an 18.3% stake in the company. At the end of 2021, PepGen had $132.8 million in cash, according to the prospectus. Combined with the IPO proceeds, PepGen plans to spend approximately $70 million to complete Phase 1 testing of PGN-EDO51 and to proceed with a planned Phase 2 study. An additional $45 million was set aside to complete a Phase 1/2 clinical trial of PGN-EDODM1, while approximately $30 million was earmarked for further development of its drug pipeline and platform. After the IPO, PepGen estimates its cash will put the company into the first half of 2025.
Bausch + Lomb raises $630M to return public markets
Bausch + Lomb is trading on the New York Stock Exchange again after completing its initial public offering, which came 15 days after the iconic ophthalmic products company went private.On Thursday night, the company Pricing Issue 35 million shares at $18 per share, well below $21 to $24 price range The company has previously set up. In addition to its listing on the New York Stock Exchange, Vaughan, Ontario-based Bausch & Lomb is also listed on the Toronto Stock Exchange.
this Bausch & Lomb IPO It marks the separation of the company from Bausch Health Companies (formerly Valeant Pharmaceuticals), which acquired the company in 2013. Originally taken private in 2007, Bausch + Lomb was acquired by private equity firms for $4.7 billion. Bausch + Lomb will not receive any IPO proceeds, which will go to Bausch Health. Ahead of the January IPO filing, Bausch Health CEO Joe Papa says his company will use IPO cash to pay down debt.
