This study will look at how well a drug that reduced the amount of oxalate in the body works in patients that have kidney disease and need dialysis treatment. People with kidney disease often have higher levels of oxalate in the blood. People with kidney disease are also at higher risk of having heart attacks, heart disease and strokes (these are called cardiovascular diseases). It is thought that high oxalate levels may increase the risk of these diseases. This study will investigate if this medicine can lower the amount of oxalate in the blood of dialysis patients and see if there is any change in the health of their heart. This medicine is already used for people who have high oxalate levels because of a genetic cause and has been used safely for patients on dialysis.
The study will put the participants randomly into either the group getting the study medicine or the group getting a placebo (this will be a solution of saline water). Neither participants not the doctors will know whether the drug or placebo is given until after the end of the study.
At the start of the study all the participants will have an echocardiogram (an ultrasound of the heart) and again 6 months later at the end of the study. We will also take blood tests once a month when the participants come for dialysis.

Start Date14 Apr 2024

Sponsor / Collaborator

Alnylam Pharmaceuticals, Inc.

NCT06225882 / RecruitingNot ApplicableIIT

Retrospective and Prospective Follow-up of Patients With Primary Hyperoxaluria Type 1 Treated With Lumasiran in France - DAILY-LUMA

Primary hyperoxaluria type 1 (PH1) is a rare genetic disease caused by mutation in the AGXT gene encoding the hepatic peroxisomal enzyme AGT. Reduced AGT activity results in increased glyoxylate and oxalate production, causing the formation of kidney stones, nephrocalcinosis and renal failure. Clinical trials of Lumasiran have provided information on the efficacy and safety of Lumasiran in the treatment of primary hyperoxaluria type 1. However, they do not provide data on long-term efficacy, safety and patient management. As part of the post-marketing follow-up of Lumasiran, in agreement with the authorities, this study proposes a retrospective and prospective follow-up over 5 years of pediatrics and adults patients treated in France with a standardized clinical, biological and radiological follow-up. The main objective is to monitor the evolution of PH1 parameters and particularly oxaluria before and after treatment.

Start Date01 Jan 2023

Sponsor / Collaborator

Hospices Civils de Lyon

EUCTR2021-001519-10-ES / Not yet recruitingPhase 2

A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, Pharmacodynamics, and Pharmacokinetics of Lumasiran in Patients with Recurrent Calcium Oxalate Kidney Stone Disease and Elevated Urinary Oxalate Levels

Start Date25 Apr 2022

Sponsor / Collaborator

Alnylam Pharmaceuticals, Inc.

100 Clinical Results associated with Lumasiran sodium

100 Translational Medicine associated with Lumasiran sodium

100 Patents (Medical) associated with Lumasiran sodium

Literatures (Medical) associated with Lumasiran sodium

01 Oct 2024·JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION

Primary hyperoxaluria: Long‐term outcomes of isolated kidney versus simultaneous liver/kidney transplant

Article

Author: Hassan, Sara ; Ibrahim, Samar H. ; Jaoudeh, Rasha A. R. A. ; Hentz, Roland C. ; Habash, Nawras W. ; Sas, David J.

Abstract:

Objectives:

To compare long‐term transplant outcomes (organ rejection and retransplant) of simultaneous liver/kidney transplant (SLK) versus isolated kidney transplant (IK) for patients with primary hyperoxaluria (PH).

Methods:

The Rare Kidney Stone Consortium PH registry was queried to identify patients with PH who underwent SLK or IK from 1999 to 2021. Patient characteristics and long‐term transplant outcomes were abstracted and analyzed. Statistical comparisons were performed with Kaplan–Meier plots and Cox proportional hazards models.

Results:

We identified 250 patients with PH, of whom 35 received care at Mayo Clinic and underwent SLK or IK. Patients who underwent SLK as their index transplant had lower odds of kidney rejection than did those who underwent IK (hazard ratio [HR], 0.29; 95% confidence interval [CI], 0.08–0.99; p = .048). The immunoprotective effect of concomitant liver and kidney transplant appeared to enhance outcomes for patients with PH. Additionally, the odds of retransplant were significantly lower for patients who underwent SLK as their index transplant than for those who underwent IK (HR, 0.08; 95% CI, 0.02–0.42; p = .003). Of five patients who underwent IK and had maintained graft function for at least 5 years after transplant, three (60%) had documented vitamin B6 responsiveness.

Conclusions:

Patients with PH who underwent SLK had a lower risk of kidney rejection and retransplant than those who underwent IK. Accurate genetic assessment for vitamin B6 responsiveness may optimize IK allocation. Novel therapeutics, such as lumasiran, have been introduced as promising agents for the management of PH.

01 Jul 2024·Kidney International Reports

Efficacy and Safety of Lumasiran in Patients With Primary Hyperoxaluria Type 1: Results from a Phase III Clinical Trial

Article

Author: Hulton, Sally-Anne ; Saland, Jeffrey M ; Magen, Daniella ; Frishberg, Yaacov ; Shasha-Lavsky, Hadas ; Moochhala, Shabbir H ; Groothoff, Jaap W ; Simkova, Eva ; Willey, Richard ; Gansner, John M ; Sellier-Leclerc, Anne-Laure ; Hayes, Wesley ; Lieske, John C ; Hogan, Julien ; Coenen, Martin

Introduction:

Patients with primary hyperoxaluria type 1 (PH1), a genetic disorder associated with hepatic oxalate overproduction, frequently experience recurrent kidney stones and worsening kidney function. Lumasiran is indicated for the treatment of PH1 to lower urinary and plasma oxalate (POx).

Methods:

ILLUMINATE-A (NCT03681184) is a phase III trial in patients aged ≥6 years with PH1 and estimated glomerular filtration rate (eGFR) ≥30 ml/min per 1.73 m². A 6-month double-blind placebo-controlled period is followed by an extension period (≤54 months; all patients receive lumasiran). We report interim data through month 36.

Results:

Of 39 patients enrolled, 24 of 26 (lumasiran/lumasiran group) and 13 of 13 (placebo/lumasiran group) entered and continue in the extension period. At month 36, in the lumasiran/lumasiran group (36 months of lumasiran treatment) and placebo/lumasiran group (30 months of lumasiran treatment), mean 24-hour urinary oxalate (UOx) reductions from baseline were 63% and 58%, respectively; 76% and 92% of patients reached a 24-hour UOx excretion ≤1.5× the upper limit of normal (ULN). eGFR remained stable. Kidney stone event rates decreased from 2.31 (95% confidence interval: 1.88-2.84) per person-year (PY) during the 12 months before consent to 0.60 (0.46-0.77) per PY during lumasiran treatment. Medullary nephrocalcinosis generally remained stable or improved; approximately one-third of patients (both groups) improved to complete resolution. The most common lumasiran-related adverse events (AEs) were mild, transient injection-site reactions.

Conclusion:

In patients with PH1, longer-term lumasiran treatment led to sustained reduction in UOx excretion, with an acceptable safety profile and encouraging clinical outcomes.See for Video Abstract.

01 Jul 2024·Pediatric nephrology (Berlin, Germany)

Nephrocalcinosis can disappear in infants receiving early lumasiran therapy

Article

Author: Acquaviva-Bourdain, Cécile ; Kayal, Dima ; Sellier-Leclerc, Anne-Laure ; de Mul, Aurélie ; Cabet, Sarah ; Bacchetta, Justine

BACKGROUND:

Lumasiran is the first RNA interference (RNAi) therapy of primary hyperoxaluria type 1 (PH1). Here, we report on the rapid improvement and even disappearance of nephrocalcinosis after early lumasiran therapy.

CASE-DIAGNOSIS/TREATMENT:

In patient 1, PH1 was suspected due to incidental discovery of nephrocalcinosis stage 3 in a 4-month-old boy. Bilateral nephrocalcinosis stage 3 was diagnosed in patient 2 at 22 months concomitantly to acute pyelonephritis. Urinary oxalate (UOx) and glycolate (UGly) were increased in both patients allowing to start lumasiran therapy before genetic confirmation. Nephrocalcinosis started to improve and disappeared after 27 months and 1 year of treatment in patients 1 and 2, respectively.

CONCLUSION:

These cases illustrate the efficacy of early lumasiran therapy in infants to improve and even normalize nephrocalcinosis. As proposed in the 2023 European guidelines, the interest of starting treatment quickly without waiting for genetic confirmation may have an impact on long-term outcomes.

128

News (Medical) associated with Lumasiran sodium

25 Nov 2024

·www.businesswire.com

Alnylam Announces U.S. Food and Drug Administration Acceptance of Supplemental New Drug Application for Vutrisiran for the Treatment of ATTR Amyloidosis with Cardiomyopathy

CAMBRIDGE, Mass.--( BUSINESS WIRE )-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced that the U.S. Food and Drug Administration (FDA) has accepted for review the Company’s supplemental New Drug Application (sNDA) for vutrisiran, an investigational RNAi therapeutic in development for the treatment of ATTR amyloidosis with cardiomyopathy (ATTR-CM). Based on the Company’s use of a Priority Review Voucher, the FDA has set an action date goal of March 23, 2025, under the Prescription Drug User Fee Act (PDUFA). The FDA has informed the Company that it is not planning to hold an advisory committee meeting at this time to review the application. Vutrisiran is the generic name for AMVUTTRA ® , which is currently approved by the FDA for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults. By rapidly knocking down both mutant and wild‑type transthyretin (TTR), vutrisiran addresses the underlying cause of transthyretin amyloidosis (ATTR). If approved, vutrisiran would become the first therapeutic approved in the U.S. to treat both the polyneuropathy manifestations of hATTR and cardiomyopathy manifestations of ATTR amyloidosis. “We are pleased that the FDA has accepted our sNDA for vutrisiran for the treatment of ATTR with cardiomyopathy – a steadily progressing, debilitating and ultimately fatal disease,” said Pushkal Garg, M.D., Chief Medical Officer of Alnylam. “In HELIOS-B, treatment with vutrisiran improved cardiovascular outcomes, survival, disease progression and quality of life, as compared to placebo, in a population reflective of today’s patients on substantial background treatment. We look forward to working with the FDA to support their review of the application and bring vutrisiran to patients with ATTR-CM in the U.S. early next year.” The supplemental application to the FDA was based on positive results from HELIOS-B, a randomized, double-blind, placebo-controlled multicenter global Phase 3 study in patients with ATTR-CM. The study demonstrated favorable effects of vutrisiran on outcomes of death and cardiovascular events, functional capacity and quality of life in patients with ATTR-CM. These treatment effects were seen on top of substantial background standard of care treatments. Vutrisiran demonstrated encouraging safety and tolerability consistent with the established profile of the drug. Detailed results from the study were presented at the European Society of Cardiology Congress and simultaneously published in The New England Journal of Medicine on August 30, 2024. AMVUTTRA ® (vutrisiran) U.S. Indication and Important Safety Information Indication AMVUTTRA is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. Important Safety Information Reduced Serum Vitamin A Levels and Recommended Supplementation AMVUTTRA treatment leads to a decrease in serum vitamin A levels. Supplementation at the recommended daily allowance (RDA) of vitamin A is advised for patients taking AMVUTTRA. Higher doses than the RDA should not be given to try to achieve normal serum vitamin A levels during treatment with AMVUTTRA, as serum vitamin A levels do not reflect the total vitamin A in the body. Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g., night blindness). Adverse Reactions The most common adverse reactions that occurred in patients treated with AMVUTTRA were pain in extremity (15%), arthralgia (11%), dyspnea (7%), and vitamin A decreased (7%). For additional information about AMVUTTRA, please see the full U.S. Prescribing Information . About AMVUTTRA ® (vutrisiran) AMVUTTRA ® (vutrisiran) is an RNAi therapeutic that delivers rapid knockdown of mutant and wild-type transthyretin (TTR), addressing the underlying cause of transthyretin (ATTR) amyloidosis. Administered quarterly via subcutaneous injection, AMVUTTRA is approved and marketed in more than 15 countries for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults. Vutrisiran is also in development for the treatment of ATTR amyloidosis with cardiomyopathy (ATTR-CM), which encompasses both wild-type and hereditary forms of the disease. For more information about AMVUTTRA, including the full U.S. Prescribing Information , visit AMVUTTRA.com . About ATTR Transthyretin amyloidosis (ATTR) is an underdiagnosed, rapidly progressive, debilitating and fatal disease caused by misfolded transthyretin (TTR) proteins, which accumulate as amyloid deposits in various parts of the body, including the nerves, heart and gastrointestinal tract. Patients may present with polyneuropathy, cardiomyopathy, or both manifestations of disease. There are two different forms of ATTR – hereditary ATTR (hATTR), which is caused by a TTR gene variant and affects approximately 50,000 people worldwide, and wild-type ATTR (wtATTR), which occurs without a TTR gene variant and impacts an estimated 200,000 – 300,000 people worldwide. About RNAi RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so,” and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines known as RNAi therapeutics is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, function upstream of today’s medicines by potently silencing messenger RNA (mRNA) – the genetic precursors that encode for disease-causing or disease pathway proteins – thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases. About Alnylam Pharmaceuticals Alnylam (Nasdaq: ALNY) has led the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of people afflicted with rare and prevalent diseases with unmet need. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach yielding transformative medicines. Since its founding in 2002, Alnylam has led the RNAi Revolution and continues to deliver on a bold vision to turn scientific possibility into reality. Alnylam’s commercial RNAi therapeutic products are ONPATTRO® (patisiran), AMVUTTRA® (vutrisiran), GIVLAARI® (givosiran), OXLUMO® (lumasiran), and Leqvio® (inclisiran), which is being developed and commercialized by Alnylam’s partner, Novartis. Alnylam has a deep pipeline of investigational medicines, including multiple product candidates that are in late-stage development. Alnylam is executing on its “ Alnylam P 5 x25 ” strategy to deliver transformative medicines in both rare and common diseases benefiting patients around the world through sustainable innovation and exceptional financial performance, resulting in a leading biotech profile. Alnylam is headquartered in Cambridge, MA. For more information about our people, science and pipeline, please visit www.alnylam.com and engage with us on X (formerly Twitter) at @Alnylam , or on LinkedIn , Facebook , or Instagram . Alnylam Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. All statements other than historical statements of fact regarding Alnylam’s expectations, beliefs, goals, plans or prospects including, without limitation, Alnylam’s expectations regarding the safety and efficacy of vutrisiran for the treatment of ATTR amyloidosis with cardiomyopathy, including the safety, tolerability and favorable effects of vutrisiran on outcomes of death and cardiovascular events, functional capacity and quality of life in patients with ATTR-CM; whether the FDA will convene an advisory committee in connection with the FDA’s review of Alnylam’s supplemental application for approval of vutrisiran for the treatment of patients with ATTR-CM; the potential for vutrisiran to obtain FDA approval for the treatment of patients with ATTR-CM, and the anticipated timing of such FDA approval; and the potential for Alnylam to achieve its Alnylam P 5 x25 vision of becoming a leading biopharma company should be considered forward-looking statements. Actual results and future plans may differ materially from those indicated by these forward-looking statements as a result of various important risks, uncertainties and other factors, including, without limitation, risks and uncertainties relating to: Alnylam’s ability to successfully execute on its “ Alnylam P 5 x25 ” strategy; Alnylam’s ability to successfully demonstrate the efficacy and safety of its product candidates; the pre-clinical and clinical results for Alnylam’s product candidates, including vutrisiran; actions or advice of regulatory agencies and Alnylam’s ability to obtain regulatory approval for its product candidates, including vutrisiran, as well as favorable pricing and reimbursement; successfully launching, marketing and selling Alnylam’s approved products globally; and any delays, interruptions or failures in the manufacture and supply of Alnylam’s product candidates or its marketed products; as well as those risks more fully discussed in the “Risk Factors” filed with Alnylam’s 2023 Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC), as may be updated from time to time in Alnylam’s subsequent Quarterly Reports on Form 10-Q and in its other SEC filings. In addition, any forward-looking statements represent Alnylam’s views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements.

Clinical ResultDrug ApprovalPhase 3NDAPriority Review

14 Nov 2024

·www.globenewswire.com

Codexis Unveils Pioneering Enzymatic Synthesis Data to Enable the Future Manufacturing of RNAi Therapeutics

—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 synthesisSuccessfully attached the tri-GalNAc tissue-targeting moiety by enzymatic ligationObtained 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 98%, which is equivalent to what is seen with phosphoramidite chemistry; executed the enzymatic addition of a conjugation moiety to the lumasiran strand; and confirmed the lack of notable impurities typically observed in oligonucleotide synthesis via phosphoramidite chemistry. A recording of the presentation, along with slides and the data press release, can be found on the Codexis corporate website. 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 ContactCarrie McKim(336) 608-9706ir@codexis.com Media ContactLauren Musto(650) 421-8205media@codexis.com

OligonucleotidePhase 3Phase 2

11 Nov 2024

·www.globenewswire.com

Codexis TIDES Europe Presentations to Feature Next Step in Evolution of Enzymatic Synthesis for RNAi Therapeutics

—Spotlight Presentation to showcase four routes of synthesis of an approved siRNA therapeutic asset— —Joint poster presentation with Bachem to compare Codexis double-stranded RNA ligase to wild-type enzymes— —Management to host conference call on Thursday, November 14 to discuss data— REDWOOD CITY, Calif., Nov. 11, 2024 (GLOBE NEWSWIRE) -- Codexis, Inc. (NASDAQ: CDXS), a leading provider of enzymatic solutions for efficient and scalable therapeutics manufacturing, today announced the Company will demonstrate real-world application of its enzymatic synthesis platform via three presentations at the upcoming TIDES Europe annual meeting, being held November 12-14, 2024, in Hamburg, Germany. Codexis management will hold an investor conference call at 4:30 pm Eastern Time on November 14, 2024, to review and discuss the data presented. In a joint poster with Bachem, one of the world’s leading CDMOs in siRNA manufacturing, Codexis will feature data demonstrating the superiority of its double-stranded RNA ligase variants compared to wild-type enzymes. The company will also participate in two oral presentations. On Wednesday, November 13, 2024, a TIDES Talk will showcase the extensive capabilities of Codexis’ RNA Ligase Screening & Optimization Services, including data from real customer case studies. On Thursday, November 14, 2024, a Spotlight Presentation will showcase the abilities of the Company’s proprietary Enzyme Catalyzed Oligonucleotide (ECO) Synthesis™ manufacturing platform utilizing various combinations of sequential enzymatic synthesis, traditional phosphoramidite chemistry and enzymatic ligation to produce a commercially available siRNA therapeutic. This public demonstration will further highlight the flexibility and broad applicability of the ECO Synthesis™ platform to the manufacture of siRNA therapeutics. Attendees of the conference may visit with the Codexis team at Booth #709 in the exhibition hall. Appointments may be made in advance by contacting the business development team. Presentation Details Spotlight Presentation: Process Development for Enzymatic Synthesis of RNAi TherapeuticsDate: Thursday, November 14, 2024Time: 1:25 pm – 1:55 pm Central European Time (CET)Codexis Speaker: Derek Gauntlett, Senior Director, ECO Synthesis Process Development TIDES Talk: RNA Synthesis Using Ligation for Improved Scalability and Reduced Manufacturing CostDate: Wednesday, November 13, 2024Time: 3:55 pm – 4:10 pm Central European Time (CET)Codexis Speaker: Mathew Miller, PhD, Director, Life Science & RNA Technology Poster Presentation: Engineered dsRNA ligases can efficiently scale siRNA manufacturingTime: Duration of the ConferenceLocation: Poster & Exhibit Hall Oral presentations will take place at the Hamburg Conference Center in Hamburg, Germany. 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 these 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 98%, which is equivalent to what is seen with phosphoramidite chemistry; executed the enzymatic addition of a conjugation moiety to the lumasiran strand; and confirmed the lack of notable impurities typically observed in oligonucleotide synthesis via phosphoramidite chemistry. A recording of the presentation, along with slides and the data press release, can be found on the Codexis corporate website. 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 or replace traditional chemical synthesis; the potential of the Company’s ECO Synthesis™ platform and double-stranded RNA (dsRNA) ligase screening and optimization services to create value for Codexis and its customers by enabling commercial-scale manufacture of RNAi therapeutics; other anticipated technical and commercial milestones related to the ECO Synthesis™ platform and the dsRNA ligase program, and public announcements related thereto; 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 purity and yield 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 Codexis is unable to develop and commercialize new products for its target 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 ContactCarrie McKim(336) 608-9706ir@codexis.com Media ContactLauren Musto(781) 572-1147media@codexis.com

OligonucleotideClinical ResultPhase 3

100 Deals associated with Lumasiran sodium

External Link

KEGG	Wiki	ATC	Drug Bank
D11926	-	A16AX	DB15935

R&D Status

Approved

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Indication	Country/Location	Organization	Date
Primary Hyperoxaluria Type 1	EU	Alnylam Netherlands BV	19 Nov 2020
Primary Hyperoxaluria Type 1	IS	Alnylam Netherlands BV	19 Nov 2020
Primary Hyperoxaluria Type 1	LI	Alnylam Netherlands BV	19 Nov 2020
Primary Hyperoxaluria Type 1	NO	Alnylam Netherlands BV	19 Nov 2020

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hyperoxaluria	Phase 2	US	Alnylam Pharmaceuticals, Inc.	27 Jan 2022
Hyperoxaluria	Phase 2	BE	Alnylam Pharmaceuticals, Inc.	27 Jan 2022
Hyperoxaluria	Phase 2	IT	Alnylam Pharmaceuticals, Inc.	27 Jan 2022
Hyperoxaluria	Phase 2	ES	Alnylam Pharmaceuticals, Inc.	27 Jan 2022
Hyperoxaluria	Phase 2	CH	Alnylam Pharmaceuticals, Inc.	27 Jan 2022
Hyperoxaluria	Phase 2	GB	Alnylam Pharmaceuticals, Inc.	27 Jan 2022
Nephrolithiasis, Calcium Oxalate	Phase 2	US	Alnylam Pharmaceuticals, Inc.	27 Jan 2022
Nephrolithiasis, Calcium Oxalate	Phase 2	BE	Alnylam Pharmaceuticals, Inc.	27 Jan 2022
Nephrolithiasis, Calcium Oxalate	Phase 2	IT	Alnylam Pharmaceuticals, Inc.	27 Jan 2022
Nephrolithiasis, Calcium Oxalate	Phase 2	ES	Alnylam Pharmaceuticals, Inc.	27 Jan 2022

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03905694 (ILLUMINATE-B, Pubmed \| Front Pediatr) Manual	Phase 3	Primary Hyperoxaluria Type 1	18	Lumasiran	zvbeuwwixf(badvtnohmy) = deebrhxgpr scuccxmbdg (wgfvhjrmzc ) View more	Positive	16 Sep 2024
NCT05161936 (CTgov)	Phase 2	Hyperoxaluria \| Nephrolithiasis, Calcium Oxalate	2	Lumasiran (Lumasiran Dose 1)	xxdmjsconr(sddrydatbr) = yimtcqjhyd imtidycwxy (humvtffdhh, afewuewjqz - bmwqpkabpg) View more	-	22 May 2024
NCT05161936 (CTgov)	Phase 2	Hyperoxaluria \| Nephrolithiasis, Calcium Oxalate	2	Lumasiran (Lumasiran Dose 2)	xxdmjsconr(sddrydatbr) = wbncefpfwy imtidycwxy (humvtffdhh, nlilegtyvc - auswthiowz) View more	-	22 May 2024
NCT03350451 (Phase 2 Open-Label Extension Study, CTgov)	Phase 2	Primary Hyperoxaluria Type 1	20	Lumasiran (Lumasiran (ALN-GO1): 1.0 mg/kg QM or 3.0 mg/kg Q3M)	nrabnlexgu(egflfdclba) = kcobpsshbs mishnnoawc (bvmrmmgcut, lufkxuhuks - vgtjvewmgb) View more	-	25 Apr 2024
NCT03350451 (Phase 2 Open-Label Extension Study, CTgov)	Phase 2	Primary Hyperoxaluria Type 1	20	Lumasiran (Lumasiran (ALN-GO1): 3.0 mg/kg QM)	nrabnlexgu(egflfdclba) = bfzzjykocr mishnnoawc (bvmrmmgcut, gkxlmfopep - egtpxknohr) View more	-	25 Apr 2024
ERA2023	Not Applicable	Primary Hyperoxaluria Type 1	-	Lumasiran 6 mg/kg	ivmhlogoqw(zduaoixfoq) = sxqodaklpw efpdjixrrb (ilgawbgnte ) View more	-	14 Jun 2023
ASN2022	Not Applicable	Hyperoxaluria, Primary AGXT gene	-	Lumasiran	kzennolznf(mwhksbcdzh) = snvjvhtwtq baeuhilkqh (wyaajfheqj ) View more	Positive	05 Nov 2022
ASN2022	Not Applicable	oxalate	75	Lumasiran (Healthy Adults)	sqelqjojmq(ipouaadwlc) = iiauurzznt xjsiyvovxd (knirexrggj, 1.71 - 12.11)	Positive	05 Nov 2022
NCT03905694 (ILLUMINATE-B, Pubmed)	Phase 3	Primary Hyperoxaluria Type 1	18	Lumasiran	jenudkixmk(zvfdrqmntr) = mild, transient injection-site reactions (3 patients (17%)) eauwptqssw (erxiemweap ) View more	Positive	01 Aug 2022
FC010 (ERA2022)	Not Applicable	Primary Hyperoxaluria Type 1	25	Oxlumo (Lumasiran)	riwnztvfhl(rygpxoedex) = wmshgxdeti hfiqgmmgps (zduumkrgll ) View more	Positive	03 May 2022
FC069 (ERA2022)	Not Applicable	plasma oxalate (POx) \| spot urinary oxalate: creatinine (UOx: Cr) \| plasma glycolate	90	Lumasiran	ymyxwmdvyw(tiksqavmsz) = ranged from 20.3 to 40.3% across studies eedvngsnvf (zegdgmujix ) View more	Positive	03 May 2022
ILLUMINATE-C (ERA2022)	Phase 3	Primary Hyperoxaluria Type 1 eGFR \| POx	21	Lumasiran	wezkuvdwqb(vrfkqckudm) = ohvrpaqjdb hgtcjcauve (lkkyyvbzre, -15.16 to 81.82) View more	Positive	03 May 2022
ILLUMINATE-C (ERA2022)	Phase 3	Primary Hyperoxaluria Type 1 eGFR \| POx	21	Placebo	wezkuvdwqb(vrfkqckudm) = wgvpirgrch hgtcjcauve (lkkyyvbzre, 34.15 - 50.71) View more	Positive	03 May 2022

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