Alnylam Highlights Significant Pipeline Progress and Platform Innovation at R&D Day

Rhea-AI Summary

Alnylam Pharmaceuticals highlighted significant progress in its R&D pipeline at its R&D Day event. Key updates include:

• Phase 3 TRITON program for nucresiran in ATTR-CM and hATTR-PN, aiming for over 95% knockdown with twice-annual dosing.
• Phase 3 trial for zilebesiran to transform hypertension treatment, enrolling up to 11,000 patients globally.
• New programs for Huntington’s disease, bleeding disorders, and type 2 diabetes.
• Platform advances for improved delivery solutions and manufacturing innovations.

Data from the HELIOS-B study showed vutrisiran reduced all-cause mortality by 36% in patients with ATTR amyloidosis with cardiomyopathy. Vutrisiran is under FDA review with a target action date of March 23, 2025.

Alnylam is committed to expanding its RNAi therapeutics, targeting all major tissue types by 2030. The company will file IND applications for nine new programs by 2025, including two in new tissues, two in the CNS, and five in the liver.

The event was webcast live and a replay will be available on Alnylam's website.

Positive

• Phase 3 TRITON program for nucresiran targeting >95% knockdown.
• Vutrisiran reduced all-cause mortality by 36% in HELIOS-B study.
• Phase 3 trial for zilebesiran enrolling 11,000 patients globally.
• New programs for Huntington’s disease, bleeding disorders, type 2 diabetes.
• Platform advances for better delivery solutions and manufacturing.

Negative

• TRITON-CM trial for nucresiran not expected to complete until 2030.
• Zilebesiran Phase 3 results expected in late 2025.

Insights

Biotechnology Investment Analyst

Alnylam's R&D Day reveals a strategic evolution from a specialized rare disease company into a diversified biopharmaceutical player with multiple blockbuster opportunities. The company is executing a two-pronged strategy: fortifying its leadership in TTR amyloidosis while simultaneously expanding into larger markets like cardiovascular disease, neuroscience, and metabolic disorders.

The TRITON Phase 3 program for nucresiran represents a critical franchise-extension strategy for Alnylam's TTR portfolio. With >95% TTR knockdown and twice-annual dosing, nucresiran aims to set a new efficacy standard while improving the patient experience. This next-generation compound strategically positions Alnylam to maintain market leadership against emerging competitors like Intellia's CRISPR-based approach and Ionis/AstraZeneca's eplontersen.

The new mortality data from HELIOS-B showing a 36-39% reduction in all-cause mortality strengthens vutrisiran's value proposition ahead of its March 23rd PDUFA date. This positions vutrisiran favorably for the ATTR-CM indication, which represents a substantially larger market opportunity than polyneuropathy with approximately 250,000-500,000 patients in the US and EU combined.

The cardiovascular program for zilebesiran targets hypertension in high-risk patients – a massive market with significant unmet need. The Roche partnership brings substantial development resources and commercial infrastructure, validating Alnylam's technology while sharing risk. The upcoming 11,000-patient outcomes trial represents Alnylam's largest clinical investment to date, signaling confidence in both the mechanism and commercial opportunity.

Alnylam's neuroscience expansion demonstrates the versatility of their RNAi platform. Mivelsiran's ability to reduce soluble APPβ in CSF represents proof-of-concept for CNS delivery, while the Huntington's program leverages their partnership with Regeneron. These programs position Alnylam in high-value neurological indications with competition and significant unmet need.

The metabolic disease programs, particularly ALN-4324 for type 2 diabetes, represent Alnylam's strategic entry into blockbuster markets dominated by GLP-1 therapies. As the first potential insulin sensitizer in over 30 years, ALN-4324 could carve out a differentiated position in diabetes care, potentially as a complementary therapy to GLP-1s.

Perhaps most significantly, Alnylam's platform innovations in tissue-specific delivery and manufacturing efficiency create sustainable competitive advantages. The enzymatic ligation manufacturing approach could substantially improve production economics, enhancing margins as the company scales.

For investors, this R&D Day demonstrates Alnylam's transformation from a specialized rare disease player to a company with multiple shots on goal across diverse therapeutic areas, supported by technology that continues to expand in capability and efficiency.

– Showcases multiple potentially transformative near- and mid-stage therapies in ATTR amyloidosis, Cardiovascular Disease, and Neuroscience, each representing a blockbuster opportunity –

– Announces TRITON Phase 3 program for next-generation TTR silencer nucresiran in ATTR-CM and hATTR-PN, targeting durable franchise leadership –

– Provides details about Phase 3 cardiovascular outcomes trial for zilebesiran, poised to transform the treatment of hypertension in patients with high CV risk –

– Highlights new clinical programs, including for Huntington’s disease, bleeding disorders, and type 2 diabetes –

– Shares platform advances, including potential best-in-class delivery solutions for adipose, muscle, heart, and kidney, and for crossing the blood-brain barrier, as well as manufacturing innovations to improve efficiency –

– Company will webcast its R&D Day event today at 9:00 a.m. E.T –

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, is hosting an R&D Day today in New York City and will also webcast the event. The Company plans to showcase its R&D progress and platform innovation, including updates on multiple near- and mid-stage potentially transformative therapies that represent blockbuster opportunities as its pipeline rapidly expands across multiple therapeutic areas.

“Alnylam is driving the field of RNAi therapeutics into the future, with a sustainable innovation engine that continues to generate transformative medicines while simultaneously expanding what’s possible for RNAi with platform advances,” said Pushkal Garg, M.D., Chief Medical Officer of Alnylam. “As we advance our flagship TTR franchise, we are excited to share Phase 3 development plans for our next-generation TTR silencer, nucresiran, which has best-in-class potential. We are also providing updates on multiple potential blockbuster opportunities in cardiovascular disease and neuroscience, areas where we believe our investigational RNAi therapeutics may transform the treatment of devastating conditions that claim millions of lives each year. In addition, we are on track to meet our ambitious pipeline and platform expansion goals as we seek to address additional diseases, to deliver RNAi therapeutics to all major tissue types by 2030, and to realize the full potential of our pioneering technology.”

Nucresiran and Vutrisiran Advancements Demonstrate Durable Leadership in TTR

Alnylam scientists will provide an update on the TRITON Phase 3 program for its next-generation transthyretin (TTR) silencer, nucresiran, which has the potential for greater than 95% knockdown with twice-annual dosing. TRITON-PN will be conducted in patients with hATTR amyloidosis with polyneuropathy, with a goal of bringing nucresiran to the market as rapidly as possible. TRITON-CM will be an event-driven cardiovascular outcomes trial in patients with ATTR amyloidosis with cardiomyopathy that, if successful, is anticipated to lead to regulatory approval in approximately 2030. TRITON-CM will enroll approximately 1,200 patients with wild-type TTR or any TTR variant and confirmed cardiomyopathy, including patients on background stabilizer therapy. The primary endpoint will be a composite of all-cause mortality and cardiovascular events.

Alnylam scientists will also share new data from the landmark HELIOS-B study of vutrisiran in ATTR amyloidosis with cardiomyopathy. In prespecified analyses with near complete data through month 42, vutrisiran reduced all-cause mortality, as compared to placebo, by 36% in the overall population and by 39% in the monotherapy population, further supporting the primary analysis presented last year at the European Society of Cardiology and published in The New England Journal of Medicine. Vutrisiran is currently under review for the treatment of ATTR amyloidosis with cardiomyopathy by the U.S. Food and Drug Administration, with a Prescription Drug User Fee Act (PDUFA) target action date of March 23, 2025.

Studies Position Zilebesiran to Transform the Treatment of Hypertension

Alnylam scientists will share key design elements of a pivotal Phase 3 trial of zilebesiran, set to begin later this year, to explore the impact of continuous control of blood pressure on cardiovascular outcomes. The Phase 3 trial will be a global, event-driven trial that will enroll up to 11,000 patients in more than 30 countries. Participants must be on at least two background antihypertensive agents, have uncontrolled hypertension, and have established cardiovascular disease or be at risk of developing cardiovascular disease. The primary endpoint will be 4-point MACE, a composite of non-fatal myocardial infarctions, non-fatal strokes, cardiovascular deaths, and hospitalizations for heart failure or urgent heart failure visits.

Enrollment is now complete for the KARDIA-3 Phase 2 trial evaluating zilebesiran in combination with at least two antihypertensives in high cardiovascular risk patients with uncontrolled hypertension. This patient population in KARDIA-3 is similar to the one currently planned for the Phase 3 cardiovascular outcomes trial. The results of KARDIA-3 – expected in the second half of 2025 – will further inform the design of the Phase 3 trial. Zilebesiran is being co-developed and co-commercialized by Alnylam and Roche.

Neuroscience Franchise Expands as Encouraging Clinical Data Continue to Emerge

Alnylam scientists will share additional data from both the single-ascending dose and multiple dose parts of its Phase 1 study of mivelsiran in early-onset Alzheimer’s disease, which further demonstrate potent and durable reduction of soluble APPβ – a key marker of target engagement – in the cerebrospinal fluid as well as an encouraging safety profile. Alnylam is also evaluating mivelsiran as a potential treatment for cerebral amyloid angiopathy, a major cause of hemorrhagic stroke, which is the most severe form of stroke.

Alnylam scientists will also present an update on the new ALN-HTT02 program, which has a highly differentiated exon-1-targeting approach to lower huntingtin (HTT) for Huntington’s disease, a progressive, fatal disorder. The Phase 1b single-ascending-dose study in adult patients with Huntington’s disease continues to progress. Alnylam expects to share substantial progress from the study at a medical congress in 2026. ALN-HTT02 is being developed in partnership with Regeneron.

Emerging Clinical Programs Position Alnylam for Sustained Growth

Alnylam scientists will share updates on several other programs that recently entered the clinic. Alnylam is on track to meet its ambitious “2-2-5” pipeline and platform expansion goal announced at R&D Day in 2023. This includes filing Investigational New Drug (IND) applications for nine new Alnylam-led programs by the end of 2025, including two in new tissues, two in the central nervous system (CNS), and five in the liver.

Metabolic Disorders

Alnylam scientists will share data on ALN-4324, which targets GRB14 for the treatment of type 2 diabetes and has the potential to be the first insulin sensitizer approved in more than 30 years. At R&D Day, Alnylam will present preclinical data that demonstrate the potential for a highly desirable product profile, including approximately 90% knockdown of the target 22 days after a low-dose, subcutaneous injection, and improved insulin sensitivity without weight gain. Alnylam will also present updates on several obesity programs: INHBE in the liver, and its first adipose-directed target, ACVR1C, as well as combinations of targets. These programs have the potential to improve on the tolerability and quality of weight loss achieved by currently available therapies.

ALN-6400 and Bleeding Disorders

Alnylam scientists will present an update on ALN-6400, which targets liver-derived plasminogen and could represent a potential universal hemostatic agent for the treatment of bleeding disorders without the risk of thrombosis. More than 3 million people in the U.S. are affected by bleeding disorders, and treatment options are limited. Data will be shared from the first cohort of participants in the Phase 1 study, demonstrating favorable impact on an ex-vivo hemostasis assay.

Alnylam Platform Innovation Will Drive the RNAi Revolution into the Future

Alnylam will strive to continue to provide best-in-class delivery solutions as it extends the applications for RNAi therapeutics. The Company’s vision is to unlock every major tissue for RNAi therapeutics by 2030. Alnylam scientists will present new preclinical data on delivery solutions with best-in-class potential for adipose, muscle, heart, and kidney tissue. The Company will also share an update on its approach to crossing the blood-brain barrier, as well as emerging technology to enable combination therapy and innovation in manufacturing with enzymatic ligation. Enzymatic ligation has the potential to revolutionize the manufacturing of RNAi therapeutics to meet growing demand and improve efficiency.

R&D Day Webcast Information

The Company’s R&D Day event will be held today, Tuesday, February 25, from 9:00 a.m. to 1:00 p.m. ET and will include a live video stream on the Investors section of the Company’s website, investors.alnylam.com/events. A replay will be available on the Alnylam website within 48 hours after the event. Presentations showcased during the event will be featured on the Capella section of Alnylam’s website.

About RNAi Therapeutics

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 Pharmaceuticals (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 P⁵x25” 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, statements regarding the potential for Alnylam to identify new potential drug development candidates and to advance its research and development programs, including statements regarding the number of INDs that Alnylam intends to file, the timing of initiation of any of Alnylam’s clinical trials, and the achievement of pipeline milestones and data, including relating to ongoing or planned clinical trials of nucresiran, zilebesiran, mivelsrian, ALN-HTT02, ALN-6400 and other product candidates; Alnylam’s planned achievement of its “Alnylam P⁵x25” strategy; Alnylam’s ability to obtain approval for new commercial products or additional indications for its existing products, including AMVUTTRA in ATTR-CM; Alnylam’s expectations regarding the safety and efficacy of AMVUTTRA for the treatment of ATTR-CM and the potential for TTR silencers to become a standard of care treatment for ATTR-CM; the potential for additional classes of therapeutics to complement silencer treatment for ATTR amyloidosis; the size of the commercial opportunities for Alnylam’s current and any future products, and the addressable markets for such products; the potential attributes and product profiles of any of Alnylam’s product candidates, including statements regarding the potential efficacy and safety of any of Alnylam’s product candidates, the potential for any of Alnylam’s product candidates to be a transformative therapy and to represent a potential blockbuster opportunity, the potential for zilebesiran to continuously control blood pressure and to transform the treatment of hypertension in patients with high CV risk, the potential of nucresiran to be a best-in-class therapeutic, the potential of ALN-4324 to be the first insulin sensitizer approved in more than 30 years, the potential for any of Alnylam’s obesity programs to improve on the tolerability and quality of weight loss achieved by currently available therapies, and the potential for ALN-6400 to represent a universal hemostatic agent for the treatment of bleeding disorders without the risk of thrombosis; Alnylam’s ability to address additional diseases and to deliver RNAi therapeutics to all major tissue types by 2030 and to realize the full potential of its pioneering technology; Alnylam’s ability to develop best-in-class delivery solutions for adipose, muscle, heart, and kidney, and for crossing the blood-brain barrier; Alnylam’s ability to further innovation and improve efficiency in manufacturing with enzymatic ligation; and the potential of enzymatic ligation to revolutionize the manufacturing of RNAi therapeutics to meet growing demand and improve efficiency, 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 P⁵x25” goals; Alnylam’s ability to discover and develop novel drug candidates and delivery approaches and successfully demonstrate the efficacy and safety of its product candidates; the pre-clinical and clinical results for Alnylam’s product candidates; actions or advice of regulatory agencies and Alnylam’s ability to obtain and maintain regulatory approval for its product candidates, as well as favorable pricing and reimbursement; successfully launching, marketing and selling Alnylam’s approved products globally and successfully competing against companies commercializing products competitive with our approved products; delays, interruptions or failures in the manufacture and supply of Alnylam’s product candidates or its marketed products; obtaining, maintaining and protecting intellectual property; Alnylam’s ability to successfully expand the approved indications for AMVUTTRA; Alnylam’s ability to manage its growth and operating expenses through disciplined investment in operations and its ability to achieve a self-sustainable financial profile in the future; Alnylam’s ability to maintain strategic business collaborations; Alnylam’s dependence on third parties for the development and commercialization of certain products, including Roche, Novartis, Sanofi, Regeneron and Vir; the outcome of litigation; the potential risk of future government investigations; the potential risk of delays with research collaborators and government agencies that Alnylam depends on arising from decisions by the U.S federal government to decrease financial support and staffing; as well as those risks more fully discussed in the “Risk Factors” filed with Alnylam’s most recent Annual Report on Form 10-K filed with the SEC and in its other SEC filings. In addition, any forward-looking statements represent Alnylam’s views only as of the date of this presentation and should not be relied upon as representing Alnylam’s views as of any subsequent date. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements.

View source version on businesswire.com: https://www.businesswire.com/news/home/20250225255910/en/

Alnylam Pharmaceuticals, Inc.

Christine Regan Lindenboom

(Investors and Media)

617-682-4340



Josh Brodsky

(Investors)

617-551-8276

Source: Alnylam Pharmaceuticals, Inc.

FAQ

What is the significance of the nucresiran Phase 3 TRITON program for ALNY?

The TRITON program for nucresiran aims for over 95% knockdown with twice-annual dosing, potentially enhancing Alnylam's leadership in TTR silencing.

How did vutrisiran perform in the HELIOS-B study according to ALNY's R&D Day?

Vutrisiran reduced all-cause mortality by 36% in patients with ATTR amyloidosis with cardiomyopathy.

What are the goals of Alnylam's zilebesiran Phase 3 trial?

The Phase 3 trial for zilebesiran aims to transform hypertension treatment, enrolling up to 11,000 patients globally.

What new programs did ALNY announce at its R&D Day?

Alnylam announced new programs for Huntington’s disease, bleeding disorders, and type 2 diabetes.

What are Alnylam's platform advances discussed at the R&D Day?

Alnylam's platform advances include improved delivery solutions and manufacturing innovations for RNAi therapeutics.

When is vutrisiran expected to receive FDA approval?

Vutrisiran is under FDA review with a target action date of March 23, 2025.