Prime Medicines Files for IPO, Revealing 18-Program Pipeline and First Patent – Genetic Engineering & Biotechnology News

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David R. Liu, PhD, Prime Medicine co-founder

Prime Medicine which applies a “search and replace” approach to gene editing, has disclosed plans to go public through an initial public offering (IPO) whose value has been speculated may reach $200 million—no small sum at a time when IPO activity has all but dried up in the current bear market.

Without spelling out a specific amount, Prime said net proceeds from the IPO would in part fund continued research and development (R&D) of its immediate target indications, including through achieving preclinical proof-of-concept in several unspecified target indications.

Prime also plans to use part of its proceeds for general corporate purposes, as well as to develop its early-stage manufacturing processes and build out a dedicated chemistry facility for its medicinal chemistry, process development, and analytical chemistry groups—“including a non-GMP piloting lab for making guide RNA, mRNA and synthesizing lipids to support our research activities,” the company stated in its Form S-1 Registration Statement, filed Friday after the close of the markets.

“We are committed to developing safe and efficient therapeutics using Prime Editing approaches to address high unmet need across a broad spectrum of diseases, from rare genetic diseases to severe, chronic and acute diseases, and ultimately to prevent disease before it occurs,” Prime stated. “We believe our in-licensed and company-owned Prime Editing technology has transformative potential that could change the course of how disease is treated and overcome the challenges associated with current genetic therapies.”

Renaissance Capital, which tracks the IPO market, estimated that Prime’s IPO “could raise up to $200 million,” making it among the year’s three largest initial public offerings for a biotech company, following vision care drug/device developer Bausch + Lomb ($630 million gross proceeds) and vaccine developer HilleVax (also $200 million).

Prime Medicine was co-founded by gene editing pioneer David Liu, PhD, and Andrew Anzalone, MD, PhD, who conceived of and developed the company’s technology while he was a Jane Coffin Childs Memorial Fund Postdoctoral Fellow in Liu’s laboratory, and is now Head of the Prime Editing Platform.

The technology behind Prime Medicine was first disclosed publicly in October 2019, when Liu and colleagues at the Broad Institute of MIT and Harvard published a paper in Nature that laid out a new mechanism for genome editing called “prime editing” that did not make double-strand breaks in the target sequence or use a donor DNA template.

“This is the beginning of an aspiration to make any DNA change in any position of a living cell or organism,” Liu told GEN at the time. Liu is the Richard Merkin professor, director of the Merkin Institute of Transformative Technologies in Healthcare, core institute member, and vice chair of the faculty at the Broad Institute, as well as the Thomas Dudley Cabot Professor of the Natural Sciences at Harvard University, and a Howard Hughes Medical Institute (HHMI) investigator.

First patent

The company in-licenses its Prime Editing technology from the Broad Institute—including U.S. Patent No. 11,447,770, covering methods of using Prime Editors, granted on September 20 and expiring in 2040.

Andrew Anzalone, MD, PhD, Head of the Prime Editing Platform at Prime Medicine

“The ‘770 Patent is the first issued Prime Editing patent in our licensed patent portfolio, and we believe it will be instrumental in protecting our Prime Editing platform and pipeline of gene editing programs,” according to Prime.

Prime began operations in the summer of 2020 and emerged from stealth mode in July 2021 by announcing that it had completed $315 million in financing, consisting of a $115 million Series A round and a $200 million series B round.

Prime Medicine applies a next-generation genome editing technology that it likens to the “search and replace” function of a word processor, only with DNA. The company trains its searching and replacing on disease-causing genetic sequences at their precise location in the genome, without resulting in double-strand DNA breaks that cause unwanted cellular changes.

“Prime Editing technology has the ability to repair diverse mutations, including all types of point mutations, deletion mutations, insertion and duplication mutations and insertion-deletion mutations,” the company stated. “Our analysis of more than 75,000 pathological, or disease-causing, mutations found in the National Center for Biotechnology Information ClinVar Database shows that those addressable by Prime Editing technology account for approximately 90 percent of genetic variants associated with disease.

“As such, we believe Prime Editing technology has the theoretical potential for repairing approximately 90 percent of known disease-causing mutations across many organisms, organs and cell types,” Prime added.

Pipeline of 18 programs

Included within the Registration Statement is details of Prime’s pipeline of 18 programs—all of which are in discovery phases. Half of them (nine programs) are categorized within its “immediate” strategic category, and consist of programs targeting:

  • Blood disorders—including sickle cell disease (partnered with Beam Therapeutics), chronic granulomatous disease (by precisely correcting the ΔGT mutation in one copy of the NCF1gene to restore p47phox protein expression and NOX2 activity), and Fanconi anemia. All programs apply ex vivo delivery.
  • Liver disorders—including Wilson’s disease (by correcting mutations ATP7B H1069Q and R778L in hepatocytes of the liver at their genomic location) and glycogen storage disease 1b. Both programs apply lipid nanoparticle (LNP) delivery.
  • Eye disorders—including retinitis pigmentosa programs focused on rhodopsin (by correcting the RHO P23H mutation in rod photoreceptors of the retina at their natural genomic location) and Usher syndrome, both applying adeno-associated virus (AAV) delivery.
  • Ear disorders—including Usher syndrome, type 3 and non-syndromic hearing loss targeting the gap junction protein beta 2 (GJB2) gene. Both programs apply AAV delivery.

The rest of Prime’s pipeline includes programs targeting Duchenne muscular dystrophy (AAV delivery), cystic fibrosis (LNP delivery), and seven repeat expansion disease-targeting programs.

Of those, one targets Fuchs’ endothelial corneal dystrophy (viral and non-viral delivery approaches), while the other six target neuromuscular disorders: Friedreich’s Ataxia (by correcting repeat expansions in the FXN gene), myotonic dystrophy type 1 (by correcting repeat expansions in the DMPK gene), and amyotrophic lateral sclerosis (ALS; applying both viral and non-viral approaches); oculopharyngeal muscular dystrophy (LNP delivery); and Huntington’s disease (delivery to be determined).

“Because biotechnology companies can only initiate therapeutic programs for a subset of pathogenic mutations and the associated diseases, we have chosen to strategically focus on disease settings where we believe that Prime Editing technology could offer compelling advantages over both current standard-of-care and novel therapeutic modalities in development,” Prime stated.

Prime finished the first half of this year with a net loss of $53.188 million, down from a net loss of $86.044 million during January-June 2021. The company ended last year with a net loss of $165.367 million. As of June 30, Prime had an accumulated deficit of $224.6 million.

The company has grown its workforce to more than 135 people as of July 31, with plans to expand its workforce significantly: “Key steps in our company growth include announcing shortly our permanent site in Cambridge that will enable us to grow beyond 200 people,” according to the registration statement.

Prime has filed paperwork with the U.S. Securities and Exchange Commission to sell its first publicly-traded stock on The Nasdaq Global Market under the symbol PRME.