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Codexis Presents Groundbreaking Enzymatic Synthesis Data at TIDES USA Annual Meeting

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Codexis, Inc. (NASDAQ: CDXS), announced it has successfully synthesized an oligonucleotide via an enzymatic route to support RNA-based therapeutics manufacturing. Data highlighting this historic manufacturing milestone are being presented today in a Spotlight Presentation at the TIDES USA annual meeting taking place in Boston, MA, and virtually May 14 – 17, 2024.

“The data presented today by Codexis are truly unprecedented—I believe this is the first enzymatic synthesis of a full-length oligonucleotide from starting material through the attachment of a conjugation moiety. This milestone provides meaningful proof of process to industry that there are alternative manufacturing methods available as the demand for RNAi therapeutics increases. The ECO Synthesis™ manufacturing platform has the potential to be a scalable and sustainable way to manufacture this important and growing new class of medicines,” said John Maraganore, PhD, Founder and Former Chief Executive Officer at Alnylam Pharmaceuticals and founding member of Codexis’ Strategic Advisory Board.

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Codexis Enzymatically Synthesizes Fully Modified RNA Oligonucleotide

During the presentation, Codexis will showcase data on the enzymatic synthesis of a known siRNA oligonucleotide that incorporates the nucleotide modifications most frequently found in approved therapeutic assets today. This includes the synthesis of siRNA compounds using the Company’s Enzyme Catalyzed Oligonucleotide (ECO) Synthesis™ manufacturing platform from a starter oligonucleotide to the inclusion of a conjugation moiety. This final step primes the oligonucleotide for the attachment of a customer’s proprietary targeting moiety to enable direct delivery of the therapeutic agent to the desired cells. Key data from the presentation noted that the ECO Synthesis™ manufacturing platform:

  • Incorporated RNA bases with common modifications used in current siRNA therapeutic assets.
  • Achieved coupling efficiency greater than 98%.
  • Executed the enzymatic addition of a conjugation moiety.
  • Confirmed lack of notable impurities typically observed in phosphoramidite chemistry synthesis

Now that Codexis has successfully achieved this important technical milestone, the Company is continuing process development to optimize yield, purity and quality with the goal of providing customers with siRNA material of comparable or better quality to phosphoramidite chemistry for preclinical testing.

Codexis Launches RNA Ligase Screening and Optimization Services

Codexis also today announced the launch of its RNA Ligase Screening and Optimization Services. An overview of this new offering will be highlighted during a TIDES Talk session on Thursday, May 16, 2024.

During phosphoramidite chemical synthesis of RNA, each nucleotide added to the growing oligonucleotide amplifies inherent coupling errors, leading to a decrease in the yield of the desired full-length RNA construct. By utilizing a ligation approach, multiple short, single-stranded RNA (ssRNA) fragments can be synthesized, via phosphoramidite chemistry or the ECO Synthesis ™ manufacturing platform, then duplexed and ligated together with an ecoRNA™ double-stranded ligase to form the desired double-stranded RNA (dsRNA) construct. This method provides the potential for higher purity and yield, which allows for increased scalability and reduced manufacturing costs.

As part of Codexis’ Center of Excellence for Enzymatic RNA Synthesis, the Company provides RNA ligase screening and optimization services, which include the custom evolution of dsRNA ligase enzyme variants, screening and protocol optimization for manufacturing and use of the dsRNA ligase, and research-grade RNA production, which can be used for future preclinical studies. More information on Codexis’ new RNA Ligase Screening and Optimization Services can be found in the Products & Services section of its corporate website.

“This week’s presentations clearly demonstrate our ability to make full-length oligonucleotides enzymatically. We are thrilled at the rapid progress that we’ve made on enzyme evolution, incorporation of modified nucleotides, and attachment of conjugation moieties since first unveiling the ECO Synthesis™ platform at the TIDES USA conference one year ago. Supplementing that with the launch of our RNA ligase screening and optimization program enables us to ultimately offer sequential enzymatic synthesis—potentially in combination with ligation—to deliver full-length siRNA constructs,” said Stephen Dilly, MBBS, PhD, Chief Executive Officer at Codexis. “We are hearing great excitement at these developments from our potential customers, partners and collaborators, and our team has dozens of meetings already scheduled this week to further discuss both the ECO Synthesis™ platform and our RNA ligase program with prospective CDMOs and drug developer customers.”