DNA Molecular Structure
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Pearl Bio yesterday announced that it has entered a collaboration with Merck, known as MSD outside of the United States and Canada, to discover biologic therapies comprising non-standard amino acids for drug discovery. Such synthetic biology efforts are increasing, as it’s believed that expanding the genetic code could provide new tools for the field of drug discovery.

“By encoding diverse synthetic chemistries into proteins, Pearl is able to tune half-life, target delivery to diseased cells, and attach cytotoxic payloads to tailor valuable therapeutic properties, overcoming key barriers preventing market approval,” explained Pearl Co-Founder Amy Cayne Schwartz, in a June 2023 release announcing patents.

That release also said: “Pearl’s technology preserves the natural protein activity while endowing valuable therapeutic properties to address defining challenges in biologic drug development—toxicity, stability, and targeted delivery—fast-tracking the path to market.”

Pearl exited stealth mode last year revealing investment from Khosla Ventures and a patent for encoding synthetic chemistries to engineer programmable biologics. The company’s scientific co-founders are Farren Isaacs, PhD and Michael Jewett, PhD. George Church, PhD, is an advisor.

The company’s technology base is outlined in a 2013 Science paper, in which Isaacs and Church are co-authors. They and their colleagues describe the construction and characterization of a GRO in which they replaced all known UAG stop codons. The organism was Escherichia coli MG1655, and they replaced all synonymous UAA codons, which permitted the deletion of release factor 1 and reassignment of UAG translation function. 

They write “This GRO exhibited improved properties for incorporation of nonstandard amino acids that expand the chemical diversity of proteins in vivo. The GRO also exhibited increased resistance to T7 bacteriophage, demonstrating that new genetic codes could enable increased viral resistance.”

The Merck/Pearl collaboration will initially focus on discovery and development of biologic therapies for the treatment of cancer leveraging Pearl’s GRO technology, which, in its release the company says offers “unique ability to work in both cell-based and cell-free systems and proprietary tethered ribosomes to encode synthetic monomers and target previously inaccessible epitopes.”

“We are excited to demonstrate the power of Pearl’s technology in our partnership with Merck to create multi-functionalized therapeutic candidates with tunable properties solving for some of the key shortcomings confronting biologics,” explained Cayne Schwartz.

Under the agreement, Pearl is eligible to receive payments totaling up to $1B across upfront, option and milestone payments in addition to potential royalties on sales of approved products derived from the collaboration.

“Merck is excited to collaborate with Pearl, a pioneer in developing recoded organisms, to produce novel biologics enabled by synthetic chemistries,” shared Juan Alvarez, VP of discovery biologics at Merck Research Laboratories.

In other synthetic biology deals, in January of this year, Johnson & Johnson bought Ambrx for around $2 billion. Ambrx has been using synthetic amino acids in ADCs. Also, Sanofi bought synthetic genome company Synthorx  for $2.5 billion in 2019.  

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