Codexis Unveils Pioneering Enzymatic Synthesis Data to Enable the Future Manufacturing of RNAi Therapeutics
Codexis (NASDAQ: CDXS) has unveiled groundbreaking data at TIDES Europe 2024, showcasing four routes of synthesis for an approved siRNA therapeutic asset, inclisiran. The company's ECO Synthesis™ manufacturing platform achieved >98% incorporation efficiency during sequential enzymatic oligo synthesis, operating under milder conditions than traditional methods. In collaboration with Bachem, Codexis demonstrated superior performance of their engineered double-stranded RNA ligases compared to wild-type enzymes, showing higher conversion rates and improved substrate versatility. The company plans to scale up siRNA manufacturing for preclinical testing following the completion of their ECO Synthesis Innovation Lab.
Codexis (NASDAQ: CDXS) ha svelato dati rivoluzionari al TIDES Europe 2024, presentando quattro vie di sintesi per un asset terapeutico siRNA approvato, inclisiran. La piattaforma di produzione ECO Synthesis™ dell'azienda ha raggiunto un'efficienza di incorporazione superiore al 98% durante la sintesi sequenziale di oligomeri enzimatici, operando in condizioni più miti rispetto ai metodi tradizionali. In collaborazione con Bachem, Codexis ha dimostrato prestazioni superiori delle loro ligasi di RNA doppio filamento ingegnerizzate rispetto agli enzimi di tipo selvatico, mostrando tassi di conversione più elevati e una maggiore versatilità del substrato. L'azienda prevede di scalare la produzione di siRNA per test preclinici dopo il completamento del loro ECO Synthesis Innovation Lab.
Codexis (NASDAQ: CDXS) ha revelado datos innovadores en TIDES Europe 2024, mostrando cuatro rutas de síntesis para un activo terapéutico de siRNA aprobado, inclisiran. La plataforma de fabricación ECO Synthesis™ de la compañía logró una eficiencia de incorporación superior al 98% durante la síntesis secuencial de oligos enzimáticos, funcionando bajo condiciones más suaves que los métodos tradicionales. En colaboración con Bachem, Codexis demostró un rendimiento superior de sus ligasas de ARN de doble cadena diseñadas en comparación con las enzimas tipo salvaje, mostrando tasas de conversión más altas y una mejor versatilidad del sustrato. La compañía planea aumentar la producción de siRNA para pruebas preclínicas tras la finalización de su ECO Synthesis Innovation Lab.
Codexis (NASDAQ: CDXS)는 TIDES Europe 2024에서 혁신적인 데이터를 공개하며 승인된 siRNA 치료 자산인 inclisiran에 대한 네 가지 합성 경로를 소개했습니다. 이 회사의 ECO Synthesis™ 제조 플랫폼은 전통적인 방법보다 더 온화한 조건에서 동시 효소 올리고 합성 중 98% 이상의 통합 효율을 달성했습니다. Bachem과 협력하여 Codexis는 야생형 효소에 비해 자체 설계한 이중 가닥 RNA 리게이스의 우수한 성능을 입증하였으며, 더 높은 전환율과 향상된 기질 다재다능성을 보여주었습니다. 이 회사는 ECO Synthesis Innovation Lab의 완공 후 siRNA 제조를 확대할 계획입니다.
Codexis (NASDAQ: CDXS) a dévoilé des données révolutionnaires lors du TIDES Europe 2024, présentant quatre voies de synthèse pour un actif thérapeutique siRNA approuvé, inclisiran. La plateforme de fabrication ECO Synthesis™ de l'entreprise a atteint une efficacité d'incorporation de plus de 98 % lors de la synthèse d'oligomères enzymatiques séquentiels, fonctionnant dans des conditions plus douces que les méthodes traditionnelles. En collaboration avec Bachem, Codexis a démontré une performance supérieure de ses ligases d'ARN double brin conçues par rapport aux enzymes de type sauvage, montrant des taux de conversion plus élevés et une meilleure polyvalence des substrats. L'entreprise prévoit de passer à l'échelle de la fabrication de siRNA pour des tests précliniques après l'achèvement de son ECO Synthesis Innovation Lab.
Codexis (NASDAQ: CDXS) hat auf der TIDES Europe 2024 bahnbrechende Daten vorgestellt und vier Syntheserouten für ein genehmigtes siRNA-Therapieprodukt, inclisiran, präsentiert. Die ECO Synthesis™-Fertigungsplattform des Unternehmens erreichte eine Incorporationseffizienz von über 98% während der sequenziellen enzymatischen Oligo-Synthese, betrieben unter milderen Bedingungen als traditionelle Methoden. In Zusammenarbeit mit Bachem zeigte Codexis eine überlegene Leistung seiner modifizierten doppelsträngigen RNA-Ligasen im Vergleich zu Wildtyp-Enzymen, mit höheren Umsetzungsraten und verbesserter Substratvielfalt. Das Unternehmen plant, die siRNA-Produktion für präklinische Tests nach Abschluss seines ECO Synthesis Innovation Lab zu skalieren.
- Achieved >98% incorporation efficiency in enzymatic oligo synthesis
- Successfully demonstrated four different synthesis routes for siRNA therapeutic
- Engineered ligases showed superior performance over wild-type enzymes
- Process operates under milder conditions with reduced chemical waste
- Manufacturing scale-up for preclinical testing still pending
- Process optimization for robustness and purity still required
Insights
The successful enzymatic synthesis of an approved siRNA therapeutic (inclisiran) represents a significant technical breakthrough in oligonucleotide manufacturing. The key advantages of Codexis' ECO Synthesis platform include:
- Milder aqueous conditions vs. traditional toxic chemical processes
- High incorporation efficiency of
98% - Multiple synthesis routes demonstrated
- Successful attachment of targeting moiety
This positions CDXS strongly in the growing RNA therapeutics manufacturing space. The validation from Bachem, a major CDMO, adds credibility. The platform's potential for improved product quality and reduced chemical waste could drive adoption by pharmaceutical companies developing RNA-based drugs. Near-term catalyst includes the completion of the ECO Synthesis Innovation Lab and scaling to preclinical quantities.
The environmental implications of this technology are substantial for pharmaceutical manufacturing. Traditional phosphoramidite chemistry relies heavily on toxic organic solvents and harsh chemicals, contributing significantly to pharmaceutical manufacturing waste. Codexis' aqueous-based enzymatic approach could dramatically reduce:
- Hazardous waste generation
- Environmental contamination risks
- Carbon footprint of RNA drug production
As ESG considerations become increasingly important in pharma manufacturing, this greener technology could provide Codexis with a competitive advantage and attract environmentally conscious partners and investors.
—Becomes first company to showcase four routes of synthesis for approved siRNA therapeutic asset—
—Joint poster with Bachem demonstrates superiority of Company’s double-stranded RNA ligases compared to wild-type enzymes—
—Management to host conference call today at 4:30 pm EST to discuss data—
REDWOOD CITY, Calif., Nov. 14, 2024 (GLOBE NEWSWIRE) -- Codexis, Inc. (NASDAQ: CDXS), a leading provider of enzymatic solutions for efficient and scalable therapeutics manufacturing, today announced data from three presentations at the TIDES Europe annual meeting being held November 12-14, 2024, in Hamburg, Germany. The data demonstrate the Company’s rapid advancement of its Enzyme Catalyzed Oligonucleotide (ECO) Synthesis™ manufacturing platform and establish Codexis’ position at the forefront of enzymatic synthesis technology to enable to ongoing expansion of RNAi therapeutics.
Codexis Demonstrates First-ever Enzymatic Synthesis of Approved siRNA Therapeutic
During an oral Spotlight Presentation, Codexis unveiled the successful end-to-end enzymatic synthesis of an entire approved siRNA therapeutic asset, inclisiran. Codexis enzymatically synthesized the full-length sense and antisense strands of the molecule, including the enzymatic incorporation of a tissue-targeting moiety to the sense strand. To date, this process has only been completed utilizing phosphoramidite chemistry, a process that involves the use of harsh chemical conditions and vast amounts of toxic organic solvents. By contrast, Codexis’ ECO Synthesis manufacturing platform operates under milder, aqueous conditions, that improves product quality and dramatically decreases chemical waste production.
In addition to this fully enzymatic route of synthesis, the Company demonstrated similar outcomes utilizing three routes of enzymatic ligation to produce the siRNA therapeutic asset, combining oligonucleotide fragments made by sequential enzymatic synthesis and traditional phosphoramidite chemistry. Key data from the presentation include:
- Achieved incorporation efficiency of >
98% during sequential enzymatic oligo synthesis - Successfully attached the tri-GalNAc tissue-targeting moiety by enzymatic ligation
- Obtained full-length oligonucleotides of equal quality and yields, using ligation of short fragments made with enzymes or by traditional phosphoramidite chemistry
Now that Codexis has successfully achieved this unprecedented milestone, the Company will continue to optimize its process for robustness, scaled-up quantities and improved purity with the goal of providing customers with siRNA material of comparable or better quality to phosphoramidite chemistry. The Company anticipates ramping up manufacturing of siRNA in quantities for preclinical testing following the successful build out of its ECO Synthesis Innovation Lab at the end of this year.
Codexis Double-stranded RNA Ligase Demonstrates Superior Performance to Wild-type Enzymes
Two additional presentations focused on results of direct comparisons of Codexis’ engineered double-stranded RNA (dsRNA) ligases and wild-type (WT) enzymes when used to combine short oligonucleotide fragments to synthesize full-length siRNA therapeutic compounds.
In a joint poster with Bachem, one of the world’s leading CDMOs in oligonucleotide manufacturing, the data provided compelling external validation of the superior performance of Codexis ligases over existing wild-type enzymes in use today. Codexis enzymes demonstrated superior performance over wild-type enzymes across both volumetric productivity and substrate versatility. These dsRNA ligases outperformed on multiple substrate designs and enabled a higher conversion rate of oligonucleotide fragments into siRNA at increased concentrations of raw materials.
In a separate TIDES Talk presentation, Codexis demonstrated improved performance of its dsRNA ligase over WT enzymes based on real customer case studies executed through the Company’s RNA Ligase Screening and Optimization Services, launched in May 2024. Codexis’ engineered ligases delivered robust, in-process performance, including higher substrate loading, faster reaction times and improved conversation at elevated temperatures. These data demonstrate the Company’s ability to accelerate delivery of lead ligase variants to customers and optimize process conditions for a customer’s specific asset.
The slide decks from both presentations as well as the joint poster with Bachem are now available in the Investor Relations section the Codexis corporate website, www.codexis.com/investors.
Conference Call and Webcast
Codexis management will host a conference call beginning at 4:30 pm Eastern Time on Thursday, November 14, 2024, to discuss the data presented during the conference. The live call can be accessed by dialing 877-705-2976 (domestic) or 201-689-8798 (international). A live webcast to accompany the conference call can be accessed on the Codexis Investor Relations website, where a replay will be available for 90 days. A telephone replay of the call will be available for 48 hours by dialing 877-660-6853 (domestic) or 201-612-7415 (international), access ID #13726635.
About RNAi Therapeutics Manufacturing
Ribonucleic acid (RNA) as a therapeutic modality has gained tremendous traction in recent years with the growing number of messenger RNA (mRNA) vaccines and small interfering RNA (siRNA) candidates advancing in clinical studies. However, large-scale production of RNA interference (RNAi) therapeutics using traditional chemical synthesis faces complex challenges in nucleic acid quality and quantity, as well as overall economics. With over 450 RNAi therapies currently in clinical development, including more than 40 assets in Phase 2 and Phase 3 clinical trials targeting disease indications impacting millions of patients, RNAi therapeutic demand is projected to outpace current production capabilities by the end of the decade.
About the ECO Synthesis Manufacturing Platform
Codexis’ proprietary Enzyme Catalyzed Oligonucleotide (ECO) Synthesis™ manufacturing platform is being designed to address scalability and cost limitations by potentially enabling the commercial-scale manufacture of RNAi therapeutics through an enzymatic route. The Company presented groundbreaking data at the TIDES USA 2024 annual meeting demonstrating the enzymatic synthesis of a full-length sense strand of the oligonucleotide lumasiran, a commercially available siRNA therapeutic, as well as shorter sense strand fragments of a second siRNA therapeutic asset, givosiran. The data demonstrate that Codexis consistently achieved coupling efficiency greater than
About Codexis
Codexis is a leading provider of enzymatic solutions for efficient and scalable therapeutics manufacturing that leverages its proprietary CodeEvolver® technology platform to discover, develop and enhance novel, high-performance enzymes and other classes of proteins. Codexis enzymes solve for real-world challenges associated with small molecule pharmaceuticals manufacturing and nucleic acid synthesis. The Company is currently developing its proprietary ECO Synthesis™ manufacturing platform to enable the scaled manufacture of RNAi therapeutics through an enzymatic route. Codexis’ unique enzymes can drive improvements such as higher yields, reduced energy usage and waste generation, improved efficiency in manufacturing and greater sensitivity in genomic and diagnostic applications. For more information, visit https://www.codexis.com.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. In some cases, you can identify forward-looking statements by terminology such as “aim,” “anticipate,” “assume,” “believe,” “contemplate,” “continue,” “could,” “design,” “due,” “estimate,” “expect,” “goal,” “intend,” “may,” “objective,” “plan,” “positioned,” “potential,” “predict,” “seek,” “should,” “suggest,” “target,” “on track,” “will,” “would” and other similar expressions that are predictions of or indicate future events and future trends, or the negative of these terms or other comparable terminology. To the extent that statements contained in this press release are not descriptions of historical facts, they are forward-looking statements reflecting the current beliefs and expectations of management, including, but not limited to, the ability of an enzymatic oligonucleotide synthesis process to complement, replace or improve upon traditional chemical synthesis; the potential of the Company’s ECO Synthesis™ platform and double-stranded RNA (dsRNA) ligase screening and optimization services to meet customers’ needs and to create value for Codexis and its customers by enabling commercial-scale manufacture of RNAi therapeutics; completion of the ECO Synthesis Innovation Lab by the end of 2024, and other anticipated technical and commercial milestones related to the ECO Synthesis™ platform and the dsRNA ligase program, and public announcements related thereto; ability of the Company to obtain new development collaborators on its ECO Synthesis technology; the potential for the Company’s dsRNA ligases to have improved scalability and reduced manufacturing costs compared to wild types or non-ligation methods; potential details and features of the ECO Synthesis™ platform such as it being scalable and able to reduce manufacturing costs, as well as having higher quality, purity and yield, and improved sustainability than existing methods; and the future demand for RNAi therapeutics. You should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties and other factors that are, in some cases, beyond Codexis’ control and that could materially affect actual results. Factors that could materially affect actual results include, among others: Codexis’ dependence on its licensees and collaborators; if any of its collaborators terminate their development programs under their respective license agreements with Codexis; Codexis may need additional capital in the future in order to expand its business; if Codexis is unable to successfully develop new technology such as its ECO Synthesis™ manufacturing platform and dsRNA ligase; Codexis’ dependence on a limited number of products and customers, and potential adverse effects to Codexis’ business if its customers’ products are not received well in the markets; whether the end markets for Codexis’ customers’ products develop and remain viable; if competitors and potential competitors who have greater resources and experience than Codexis develop products and technologies that make Codexis’ products and technologies obsolete; Codexis’ ability to comply with debt covenants under its loan facility; if Codexis is unable to accurately forecast financial and operational performance; and market and economic conditions may negatively impact Codexis business, financial condition and share price. Additional information about factors that could materially affect actual results can be found in Codexis’ Annual Report on Form 10-K for the year ended December 31, 2023 filed with the Securities and Exchange Commission (“SEC”) on February 28, 2024 and in Codexis’ Quarterly Report on Form 10-Q for the quarter ended September 30, 2024 filed with the SEC on October 31, 2024, including under the caption “Risk Factors,” and in Codexis’ other periodic reports filed with the SEC. Codexis expressly disclaims any intent or obligation to update these forward-looking statements, except as required by law.
For More Information
Investor Contact
Carrie McKim
(336) 608-9706
ir@codexis.com
Media Contact
Lauren Musto
(650) 421-8205
media@codexis.com
FAQ
What breakthrough did Codexis (CDXS) announce at TIDES Europe 2024?
What efficiency rate did Codexis (CDXS) achieve in their enzymatic oligo synthesis?
How does Codexis (CDXS) ECO Synthesis platform compare to traditional methods?
What were the results of Codexis (CDXS) collaboration with Bachem?
