Two Part (Double-blind Inclisiran Versus Placebo [Year 1] Followed by Open-label Inclisiran [Year 2]) Randomized Multicenter Study to Evaluate Safety, Tolerability, and Efficacy of Inclisiran in Children (2 to Less Than 12 Years) With Homozygous Familial Hypercholesterolemia and Elevated LDL-cholesterol

This is a pivotal phase III study designed to evaluate safety, tolerability, and efficacy of inclisiran in children (aged 2 to <12 years) with homozygous familial hypercholesterolemia (HoFH) and elevated low density lipoprotein cholesterol (LDLC).

Start Date31 Mar 2025

Sponsor / Collaborator

Novartis Pharmaceuticals Corp.

NCT06770543

/ Not yet recruitingNot Applicable

Regulatory Post-Marketing Surveillance (rPMS) Study for Leqvio® Pre-filled Syringe(Inclisiran Sodium)

This non-interventional study is a mandatory regular Post Marketing Surveillance(rPMS) granted by the Korean health authorities, and is conducted to assess the effectiveness and safety of Leqvio® Pre-filled Syringe(inclisiran sodium) in routine clinical practice for the approved indications (primary hypercholesterolemia or mixed dyslipidemia).

Start Date29 Mar 2025

Sponsor / Collaborator

Novartis Pharmaceuticals Corp.

NCT06501443

/ Not yet recruitingPhase 4

Latin America Lipid Optimization After Acute Event in Patients With AthErosclerotic CardiovasculaR DiseaSe and High LDL-C

This is an open label, patient-level 1:1 randomized clinical trial in a multi-country study aiming to evaluate the real-world impact of inclisiran + Usual Care (UC) vs UC alone on LDL-C lowering, patient-reported outcomes, and healthcare resource utilization in an in-hospital population of patients, admitted during the acute setting, stabilized and before discharge, following an acute cardiovascular event.

Start Date17 Jan 2025

Sponsor / Collaborator

Novartis Pharmaceuticals Corp.

100 Clinical Results associated with Inclisiran sodium

100 Translational Medicine associated with Inclisiran sodium

100 Patents (Medical) associated with Inclisiran sodium

349

Literatures (Medical) associated with Inclisiran sodium

01 Mar 2025·Atherosclerosis plus

Emerging oral therapeutic strategies for inhibiting PCSK9

Review

Author: Marodin, Giorgia ; Ferri, Nicola

Pharmacological inhibition of Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) have been firmly established to be an effective approach to reduce low-density lipoprotein (LDL) cholesterol levels and cardiovascular events. Subcutaneous administration of monoclonal antibodies (evolocumab and alirocumab) every 2 or 4 weeks determined a 60 % reduction of LDL cholesterol levels, while the GalNac-siRNA anti PCSK9 (inclisiran) provided an effective lipid lowering activity (-50 %) after an initial subcutaneous dose, repeated after 3 months and followed by a maintenance dose every 6 months. Although these two approaches have the potentiality to bring the majority of patients at high and very-high cardiovascular risk to the appropriate LDL cholesterol targets, their cost and subcutaneous administration represent a strong limitation for their large-scale use. These problems could be overcome by the development of small chemical molecules anti PCSK9 as oral therapy for controlling hypercholesterolemia. In the present review, we summarized the pharmacological properties of oral anti PCSK9 molecules that are currently under clinical development (DC371739, CVI-LM001, and AZD0780), including the mimetic peptides enlicitide decanoate (MK-0616) and NNC0385-0434.

01 Feb 2025·DIABETES OBESITY & METABOLISM

Inclisiran versus alirocumab in improving lipid profile parameters: A systematic review and meta‐analysis

Article

Author: Saad Cleto, André ; Schirlo, João Matheus ; Sponholz Neiverth, Guinter ; Julinhaque Beraldo, Maria Luiza ; Martins, Camila Marinelli ; Beltrame, Mayara ; Oliveira Gomes, Victor Hugo ; Machozeki, Janete

Abstract:

Aims:

Dyslipidemia is a risk factor for cardiovascular diseases. Some patients are resistant to conventional treatment. In these patients, there is the possibility of using PCSK9 inhibitors. The objective of this systematic review was to compare alirocumab with inclisiran in improving the lipid profile.

Materials and Methods:

This study was carried out in accordance with Preferred Reporting Items for Systematic Review and Meta‐Analysis Protocols Statement (PRISMA) and registered with PROSPERO (CRD42024563261). The following databases were accessed on 2 July 2024: PubMed, Scopus and Web of Science. Clinical trials that evaluated the lipid profile were included. With these data, meta‐analyses were carried out seeking to evaluate the difference between the baseline and the 12‐ and 24‐week endpoints.

Results:

Initially, 1157 studies were found, of which 32 were included. In total, 30 718 patients participated in the included studies. There was a statistically significant difference, favouring alirocumab 75 mg (−51.54%, 95% confidence interval [CI] −53.43%; −49.66%), in relation to inclisiran 300 mg (−41.34%, 95% CI −50.30%; −31.34%) in reducing low‐density lipoprotein cholesterol (LDL‐C) (p = 0.05), in relation to inclisiran 200 and 300 mg in reducing total cholesterol (p < 0.01) (p < 0.01) and triglycerides (p = 0.02) (p = 0.04) in 24 weeks. Furthermore, alirocumab 150 mg was superior to both doses of inclisiran in reducing total cholesterol (p < 0.01) (p < 0.01). There was no statistically significant difference in the reduction of lipoprotein(a) by alirocumab 75 mg (−22.35%, 95% CI −24.67; −20.03) and 150 mg (−25.17%, 95% CI −30.94; −19.41) compared to inclisiran 300 mg (−13.37, 95% CI −28.66; 1.93) (p = 0.26) (p = 0.16).

Conclusion:

Alirocumab was superior to inclisiran in improving the lipid profile, especially in reducing LDL‐C, total cholesterol and triglycerides.

02 Jan 2025·Expert Opinion On Drug Safety

Statin alternatives for the treatment of hypercholesterolemia - a safety evaluation

Review

Author: Tomlinson, Brian ; Zeng, Weiwei

INTRODUCTION:

Statins are well established as the first-line treatment to reduce low-density-lipoprotein cholesterol (LDL-C) and cardiovascular (CV) events, but some patients are unable to tolerate effective doses or sometimes any dose of statins and alternative treatments may be required.

AREAS COVERED:

In this review we summarize the relevant published literature obtained from a PubMed search on the safety of statin alternatives for the treatment of hypercholesterolemia.

EXPERT OPINION:

The main alternatives to statins are ezetimibe, the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, evolocumab, alirocumab, and inclisiran, and the recently approved bempedoic acid. These have all shown an excellent safety profile and have not been associated with skeletal muscle symptoms or with increased risk of new onset diabetes and they have no major drug interactions. The injectable PCSK9 inhibitors are associated with a small increase in injection site reactions which are usually of mild or moderate intensity. Bempedoic acid is associated with a small increase in plasma uric acid and slightly increased frequency of episodes of gout in susceptible subjects. The cost and availability and the degree of lowering of LDL-C required are more likely to determine the choice of statin alternatives than the safety issues.

193

News (Medical) associated with Inclisiran sodium

12 Jan 2025

·investors.alnylam.com

Alnylam Announces Preliminary* Fourth Quarter and Full Year 2024 Global Net Product Revenues and Provides 2025 Combined Net Product Revenue Guidance and Pipeline Goals

Jan 12, 2025 – Full Year 2024 Preliminary Net Product Revenues of $1,646 Million for ONPATTRO®, AMVUTTRA®, GIVLAARI®, and OXLUMO®, Representing 33% Annual Growth – – 2025 Combined Net Product Revenue Guidance** of $2,050 Million to $2,250 Million Positions Company to Achieve Alnylam P5x25 Goal of Non-GAAP Profitability – – Robust Clinical Pipeline with Multi-Billion-Dollar Opportunities for Sustainable Growth – CAMBRIDGE, Mass. --(BUSINESS WIRE)--Jan. 12, 2025-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced its preliminary* fourth quarter and full year 2024 global net product revenues for ONPATTRO, AMVUTTRA, GIVLAARI, and OXLUMO. In addition, the Company provided 2025 net product revenue, non-GAAP operating income profitability, and pipeline goals guidance. “Alnylam’s commercial and clinical achievements in 2024 position us very well for another transformative year in 2025, as we continue to evolve into a global, top-tier biotech company,” said Yvonne Greenstreet , MBChB, Chief Executive Officer of Alnylam . “We generated net product revenues for the year of over $1.6 billion , representing growth of 33% compared to 2023, at the high end of our revised guidance range, and demonstrating the strength of our underlying hATTR-PN and Rare businesses. We expect 2025 will represent an important inflection point for our TTR franchise, with the potential launch of vutrisiran in ATTR-CM delivering significant topline growth as reflected in our net product sales guidance announced today. If we are successful in meeting this product revenue guidance, we anticipate achieving non-GAAP profitability in 2025.” Dr. Greenstreet continued, “We’re also looking forward to a year of major advancements in our pipeline and RNAi platform, with key goals outlined today. This remarkable pace of progress positions us well to finish the year achieving key Alnylam P5x25 goals and to continue delivering sustainable innovation to patients through our global commercial infrastructure, broad pipeline, and organic platform.” Preliminary Fourth Quarter and Full Year 2024 Commercial and Financial Performance* Total TTR: ONPATTRO® (patisiran) & AMVUTTRA® (vutrisiran) Preliminary* global net product revenues for ONPATTRO and AMVUTTRA for the fourth quarter were approximately $56 million and $287 million , respectively, representing together 35% total TTR annual growth compared to Q4 2023, and for the full year 2024 were approximately $253 million and $970 million , respectively, representing together 34% total TTR annual growth compared to full year 2023. Total Rare: GIVLAARI® (givosiran) & OXLUMO® (lumasiran) Preliminary* global net product revenues for GIVLAARI and OXLUMO for the fourth quarter were approximately $65 million and $44 million , respectively, representing together 18% total Rare annual growth compared to Q4 2023, and for the full year 2024 were approximately $256 million and $167 million , respectively, representing together 29% total Rare annual growth compared to full year 2023. 2025 Combined Net Product Revenue & Non-GAAP Operating Income Guidance Alnylam announced today full year 2025 combined net product revenue guidance for ONPATTRO, AMVUTTRA (PN & CM**), GIVLAARI and OXLUMO of $2,050 million to $2,250 million , representing combined full year growth compared to 2024 of 31% at the mid-point of the guidance range. On a franchise level, the guidance is broken down as follows: Total TTR (ONPATTRO, AMVUTTRA (PN & CM**)): $1,600 million to $1,725 million , representing full year growth compared to 2024 of 36% at the mid-point of the guidance range. Total Rare (GIVLAARI, OXLUMO): $450 million to $525 million , representing full year growth compared to 2024 of 15% at the mid-point of the guidance range. In addition, the Company anticipates delivering non-GAAP operating income profitability in 2025. The Company plans to provide additional guidance for collaboration and royalty revenue and operating expenses at the time fourth quarter and full year 2024 earnings are released. 2025 Product and Pipeline Goals Vutrisiran – an RNAi therapeutic marketed in various countries globally as a treatment of adults with hATTR amyloidosis with polyneuropathy, and in development for the treatment of adults with ATTR amyloidosis with cardiomyopathy. Alnylam expects to: Achieve U.S. Food and Drug Administration (FDA) approval of the supplemental New Drug Application for the treatment of adults with ATTR amyloidosis with cardiomyopathy by the PDUFA target action date of March 23, 2025 . Secure additional global approvals and reimbursement in Japan and the EU for the treatment of adults with ATTR amyloidosis with cardiomyopathy in the second half of 2025. Nucresiran (ALN-TTRsc04) – an investigational RNAi therapeutic in development for the treatment of ATTR amyloidosis. Alnylam expects to: Initiate a Phase 3 study in patients with ATTR amyloidosis with cardiomyopathy in the first half of 2025. Zilebesiran – an investigational RNAi therapeutic in development for the treatment of hypertension, in collaboration with Roche. Alnylam expects to: Report results from the KARDIA-3 Phase 2 study in the second half of 2025. Initiate a Phase 3 cardiovascular outcomes trial in the second half of 2025. Mivelsiran – an investigational RNAi therapeutic in development for the treatment of Alzheimer’s disease and cerebral amyloid angiopathy (CAA). Alnylam expects to: Report interim results from Part B of the Phase 1 study in Alzheimer’s disease in the second half of 2025. Initiate a Phase 2 study in Alzheimer’s disease in the second half of 2025. ALN-6400 – an investigational RNAi therapeutic in development for the treatment of bleeding disorders. Alnylam expects to: Initiate a Phase 2 study in a bleeding disorder in the second half of 2025. In addition, the Company plans to file Investigational New Drug (IND) applications for four new Alnylam -led programs by the end of 2025. Partner-Led Program Highlights Alnylam partnered programs continue to progress, including: Fitusiran – an investigational RNAi therapeutic partnered with Sanofi in development for the treatment of hemophilia A and B, with or without inhibitors. Sanofi expects to secure FDA approval by the PDUFA target action date of March 28, 2025 . Elebsiran – an investigational RNAi therapeutic partnered with Vir Biotechnology in development for the treatment of chronic hepatitis B and chronic hepatitis delta. In 2025, Vir expects to initiate a Phase 3 chronic hepatitis delta registrational study and to report functional cure results from a Phase 2 chronic hepatitis B study. Alnylam management will discuss its preliminary 2024 net product revenues, as well as 2025 goals and guidance during a webcast presentation at the 43rd Annual J.P. Morgan Healthcare Conference in San Francisco, California tomorrow, Monday, January 13, 2025 at 9:45 am PT ( 12:45 pm ET ). 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 (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 Alnylam’s evolution into a leading, global, top-tier biotech company; Alnylam’s expectations regarding the potential approval and launch of AMVUTTRA for the treatment of ATTR amyloidosis with cardiomyopathy in the U.S. in early 2025 and in other territories in the second half of 2025; the potential that the launch of AMVUTTRA for ATTR-CM will deliver significant topline growth for Alnylam ; the potential for 2025 to be a transformative year for Alnylam and that 2025 will represent an important inflection point for Alnylam’s TTR franchise; Alnylam’s ability to deliver non-GAAP operating income profitability in 2025; the potential for 2025 to be a year of major advancements in Alnylam’s pipeline and RNAi platform; Alnylam’s potential achievement of the goals in its “Alnylam P5x25” strategy; Alnylam’s ability to continue to deliver sustainable innovation to patients through its global commercial infrastructure, broad pipeline and organic platform; the potential for Alnylam to advance its research and development programs, including its goals and expectations regarding the clinical development of vutrisiran, nucresiran, zilebesiran, mivelsiran, ALN-6400, and its earlier stage programs, and its partners’ expectations for Alnylam’s partnered programs; and Alnylam’s projected commercial and financial performance, including the expected range of net product revenues and non-GAAP operating income for 2025, 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” strategy; 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, including vutrisiran, nucresiran, zilebesiran, mivelsiran and ALN-6400; actions or advice of regulatory agencies and Alnylam’s ability to obtain and maintain 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; 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 in the future; 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 without the need for future equity financing; 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 risk of future government investigations; and unexpected expenditures; as well as those risks and uncertainties 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 other filings that Alnylam makes with the SEC . 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. This release discusses investigational RNAi therapeutics and uses of previously approved RNAi therapeutics in development and is not intended to convey conclusions about efficacy or safety as to those investigational therapeutics or uses. Vutrisiran has not been approved by any regulatory agency for the treatment of ATTR amyloidosis with cardiomyopathy. No conclusions can or should be drawn regarding its safety or effectiveness in treating cardiomyopathy in this population. There is no guarantee that any investigational therapeutics or expanded uses of commercial products will successfully complete clinical development or gain health authority approval. Use of Non-GAAP Financial Measures This press release contains a non-GAAP financial measure of non-GAAP operating income. This measure is not in accordance with, or an alternative to, GAAP, and may be different from non-GAAP financial measures used by other companies. Stock-based compensation expense is included in GAAP operating income but excluded for purposes of determining non-GAAP operating income. The Company has excluded the impact of stock-based compensation expense as it may fluctuate from period to period based on factors including the variability associated with performance-based grants for stock options and restricted stock units and changes in the Company’s stock price, which impacts the fair value of these awards. * The preliminary selected financial results are unaudited, subject to adjustment, and provided as an approximation in advance of the Company’s announcement of complete financial results in February 2025 . ** Guidance assumes FDA approval of the sNDA for vutrisiran for the treatment of adults with ATTR amyloidosis with cardiomyopathy by the March 23, 2025 PDUFA target action date. View source version on businesswire.com: https://www.businesswire.com/news/home/20250112711585/en/ Alnylam Pharmaceuticals, Inc. Christine Regan Lindenboom (Investors and Media) 617-682-4340 Josh Brodsky (Investors) 617-551-8276 Source: Alnylam Pharmaceuticals, Inc.

Phase 2Drug ApprovalFinancial StatementPhase 3Phase 1

10 Dec 2024

·www.globenewswire.com

CAMP4 Appoints John Maraganore and Rachel Meyers as Strategic Advisors

Industry veterans John Maraganore, Ph.D., and Rachel Meyers, Ph.D., to provide strategic guidance on the company’s RNA Actuating platform to develop a new class of RNA medicines that upregulate protein coding genesCAMBRIDGE, Mass., Dec. 10, 2024 (GLOBE NEWSWIRE) -- CAMP4 Therapeutics Corporation (“CAMP4”) (Nasdaq: CAMP), a clinical-stage biotechnology company developing a pipeline of regRNA-targeting therapeutics designed to upregulate gene expression with the goal of restoring healthy protein levels across a range of genetic diseases, today announced the appointments of John Maraganore, Ph.D., and Rachel Meyers, Ph.D., as strategic advisors to the Company. For nearly 20 years, Dr. Maraganore served as the founding Chief Executive Officer and Director of Alnylam where he led the company’s programs in RNA interference through global commercialization, resulting in the launch of the first four RNAi therapeutics, ONPATTRO®, GIVLAARI®, OXLUMO®, and LEQVIO®. Additionally, Dr. Meyers brings more than two decades of life sciences leadership, research, and development experience in RNA-based medicines, having spent nearly 14 years at Alnylam where she most recently served as Senior Vice President of Research and RNAi Lead Development. She currently sits on the company’s Scientific Advisory Board. “We feel privileged and are delighted to welcome Drs. Maraganore and Meyers to our CAMP4 team as strategic advisors,” said Josh Mandel-Brehm, Chief Executive Officer of CAMP4. “We view their joining the team as a testament to the promise and potential of our approach for upregulating gene expression to potentially address a broad range of diseases. As we prepare for 2025, we look forward to benefiting from their insights and expertise as we advance our efforts in bringing potentially transformative RNA medicines to patients in need of disease-modifying solutions.” Dr. Maraganore added, “The targeted upregulation of gene expression has been a long-standing challenge for the field, and by applying established and clinically validated antisense oligonucleotide technology to groundbreaking science, CAMP4 could potentially make a meaningful impact on patients across a broad range of diseases. I look forward to working with them as they pioneer the field of upregulation.” Prior to his role at Alnylam, Dr. Maraganore led the product franchises in oncology, cardiovascular, inflammatory, and metabolic diseases for Millennium Pharmaceuticals, in addition to leadership of M&A, strategy, and biotherapeutics. Earlier in his career, Dr. Maraganore invented and spearheaded the development of ANGIOMAX® (bivalirudin) for injection while at Biogen and was also a scientist at ZymoGenetics, Inc., and the Upjohn Company. He currently serves as a Venture Partner at ARCH Venture Partners, a Venture Advisor at Atlas Ventures, an Executive Partner at RTW Investments, a Senior Advisor for Blackstone Life Sciences, and a Senior Advisor for Jeffries Financial Group. Beyond his leadership roles in the investment community, Dr. Maraganore also sits on the Board of Directors for multiple publicly traded companies, including Beam Therapeutics, Kymera Therapeutics, Rapport Therapeutics, and Takeda Pharmaceuticals. He received his B.A., M.S., and Ph.D. in biochemistry and molecular biology at the University of Chicago. Dr. Meyers currently serves as a member of the Board of Directors of Korro Bio (Nasdaq: KRRO), a biopharmaceutical company focused on discovering, developing, and commercializing a new class of genetic medicines based on editing RNA, and also holds a variety of advisory roles within the biotech community. Most recently, she served as Founder and Chief Scientific Officer at Faze Medicines, a Third Rock Ventures-spawned biotech company focused on treating diseases of high unmet need through the perturbation of biomolecular condensates. Earlier in her career, Dr. Meyers was a senior scientist at Millennium Pharmaceuticals and today serves on multiple scientific advisory boards, including the National Advisory Board on Innovation and Entrepreneurship through the Department of Commerce. Furthermore, she is listed as an inventor on numerous patents and patent applications and has authored many peer-reviewed publications. Dr. Meyers received her postdoctoral training with Lew Cantley at Harvard Medical School in signal transduction and earned her Ph.D. in biology from Nobel laureate Phil Sharp at the Massachusetts Institute of Technology in in vitro transcription. She earned her BA in Biochemistry from Brandeis University. “I’ve had the unique opportunity to work alongside tremendously talented professionals who have led the shaping of the RNA medicines space,” said Dr. Meyers. “Having been at the forefront of these scientific breakthroughs, I believe now more than ever RNA-based therapies are poised to continue transforming how we treat patients with complex diseases. Having the opportunity to advise CAMP4 as they continue advancing the field is an extension of the work to which I’ve committed my career.” About CAMP4 Therapeutics CAMP4 is developing disease-modifying treatments for a broad range of genetic diseases where amplifying healthy protein may offer therapeutic benefits. Our approach amplifies mRNA by harnessing a fundamental mechanism of how genes are controlled. To amplify mRNA, our therapeutic ASO drug candidates target regRNAs, which act locally on transcription factors and are the master regulators of gene expression. CAMP4’s proprietary RAP Platform™ enables the mapping of regRNAs and generation of therapeutic candidates designed to target the regRNAs associated with genes underlying haploinsufficient and recessive partial loss-of-function disorders, of which there are more than 1,200, in which a modest increase in protein expression may have the potential to be clinically meaningful. Learn more about us at www.CAMP4tx.com and follow us on LinkedIn and X. Forward-Looking Statements This press release contains forward-looking statements which involve risks, uncertainties and contingencies, many of which are beyond the control of the Company, which may cause actual results, performance, or achievements to differ materially from anticipated results, performance, or achievements. All statements other than statements of historical facts contained in this press release are forward-looking statements. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements include, but are not limited to, statements concerning CAMP4’s plans, objectives, expectations and intentions; the timing and results of ongoing and future clinical trials, including expectations on the timing of reporting SAD and MAD data from and seeking regulatory approval for the CMP-CPS-001 trial; its growth strategy; and cash balance guidance. The forward-looking statements in this press release speak only as of the date of this press release and are subject to a number of known and unknown risks, uncertainties and assumptions that could cause the Company’s actual results to differ materially from those anticipated in the forward-looking statements, including, but not limited to: the Company’s limited operating history, incurrence of substantial losses since the Company’s inception and anticipation of incurring substantial and increasing losses for the foreseeable future; the Company’s need for substantial additional financing to achieve the Company’s goals; the uncertainty of clinical development, which is lengthy and expensive, and characterized by uncertain outcomes, and risks related to additional costs or delays in completing, or failing to complete, the development and commercialization of the Company’s current product candidates or any future product candidates; delays or difficulties in the enrollment and dosing of patients in clinical trials; the impact of any significant adverse events or undesirable side effects caused by the Company’s product candidates; potential competition, including from large and specialty pharmaceutical and biotechnology companies; the Company’s ability to realize the benefits of the Company’s current or future collaborations or licensing arrangements and ability to successfully consummate future partnerships; the Company’s ability to obtain regulatory approval to commercialize any product candidate in the United States or any other jurisdiction, and the risk that any such approval may be for a more narrow indication than the Company seeks; the Company’s dependence on the services of the Company’s senior management and other clinical and scientific personnel, and the Company’s ability to retain these individuals or recruit additional management or clinical and scientific personnel; the Company’s ability to grow the Company’s organization, and manage the Company’s growth and expansion of the Company’s operations; risks related to the manufacturing of the Company’s product candidates, which is complex, and the risk that the Company’s third-party manufacturers may encounter difficulties in production; the Company’s ability to obtain and maintain sufficient intellectual property protection for the Company’s product candidates or any future product candidates the Company may develop; the Company’s reliance on third parties to conduct the Company’s preclinical studies and clinical trials; the Company’s compliance with the Company’s obligations under the licenses granted to the Company by others, for the rights to develop and commercialize the Company’s product candidates; risks related to the operations of the Company’s suppliers; and other risks and uncertainties described in the section “Risk Factors” in the Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2024, as well as other information we file with the Securities and Exchange Commission. The forward-looking statements in this press release are inherently uncertain and are not guarantees of future events. Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond the Company’s control, you should not unduly rely on these forward-looking statements. The events and circumstances reflected in the forward-looking statements may not be achieved or occur and actual future results, levels of activity, performance and events and circumstances could differ materially from those projected in the forward-looking statements. Moreover, the Company operates in an evolving environment. New risks and uncertainties may emerge from time to time, and management cannot predict all risks and uncertainties. Investors, potential investors, and others should give careful consideration to these risks and uncertainties. Except as required by applicable law, the Company does not undertake to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. Contacts Investor Relations:Sandya von der WeidLifeSci Advisorssvonderweid@lifesciadvisors.com Media:Jason Braco, Ph.D.LifeSci Communicationsjbraco@lifescicomms.com

Executive ChangeOligonucleotide

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

100 Deals associated with Inclisiran sodium

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KEGG	Wiki	ATC	Drug Bank
-	Inclisiran sodium	C10AX	DB14901

R&D Status

Approved

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Indication	Country/Location	Organization	Date
Hypercholesterolemia	JP	Novartis Pharma KK	25 Sep 2023
Dyslipidemias	CN	Novartis Pharma AG	22 Aug 2023
Dyslipidemias	CN	Novartis Europharm Ltd.	22 Aug 2023
Primary Hyperlipidemia	US	Novartis Pharmaceuticals Corp.	07 Jul 2023
Atherosclerosis	AU	Novartis Pharmaceuticals Australia Pty Ltd.	14 Sep 2021
Heterozygous familial hypercholesterolemia	CA	Novartis Pharmaceuticals Canada, Inc.	26 Jul 2021
Hyperlipoproteinemia Type II	CA	Novartis Pharmaceuticals Canada, Inc.	26 Jul 2021
Complex dyslipidemia	EU	Novartis Europharm Ltd.	09 Dec 2020
Complex dyslipidemia	IS	Novartis Europharm Ltd.	09 Dec 2020
Complex dyslipidemia	LI	Novartis Europharm Ltd.	09 Dec 2020
Complex dyslipidemia	NO	Novartis Europharm Ltd.	09 Dec 2020
Primary hypercholesterolemia	EU	Novartis Europharm Ltd.	09 Dec 2020
Primary hypercholesterolemia	IS	Novartis Europharm Ltd.	09 Dec 2020
Primary hypercholesterolemia	LI	Novartis Europharm Ltd.	09 Dec 2020
Primary hypercholesterolemia	NO	Novartis Europharm Ltd.	09 Dec 2020

Developing

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Indication	Highest Phase	Country/Location	Organization	Date
Coronary Artery Disease	Phase 3	US	Novartis Pharmaceuticals Corp.	08 Jul 2022
Coronary Artery Disease	Phase 3	CN	Novartis Pharmaceuticals Corp.	08 Jul 2022
Coronary Artery Disease	Phase 3	JP	Novartis Pharmaceuticals Corp.	08 Jul 2022
Coronary Artery Disease	Phase 3	AR	Novartis Pharmaceuticals Corp.	08 Jul 2022
Coronary Artery Disease	Phase 3	AU	Novartis Pharmaceuticals Corp.	08 Jul 2022
Coronary Artery Disease	Phase 3	BE	Novartis Pharmaceuticals Corp.	08 Jul 2022
Coronary Artery Disease	Phase 3	BR	Novartis Pharmaceuticals Corp.	08 Jul 2022
Coronary Artery Disease	Phase 3	CA	Novartis Pharmaceuticals Corp.	08 Jul 2022
Coronary Artery Disease	Phase 3	CL	Novartis Pharmaceuticals Corp.	08 Jul 2022
Coronary Artery Disease	Phase 3	FR	Novartis Pharmaceuticals Corp.	08 Jul 2022

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03814187 (ORION-8, Pubmed \| Cardiovasc Res)	Phase 2/3	Homozygous familial hypercholesterolemia \| Atherosclerosis \| Heterozygous familial hypercholesterolemia	3,274	Inclisiran	aiykqkgwis(yuwjrqcgqr) = 5.9% of inclisiran-treated patients jqcmbkclzo (cdycgoahlg )	Positive	14 Oct 2024
ESC2024	Not Applicable	-	-	Inclisiran	codezstrvx(ktnipakmbl) = wovsubqure wjeijtujbi (tsxgecktll ) View more	-	31 Aug 2024
ESC2024	Not Applicable	-	-	Inclisiran + Usual Care	ajiamhzabi(qxpcncikgt) = Incidence of treatment-emergent adverse events (TEAEs) and serious TEAEs compared similarly between IF and UC for each subgroup (IF: 35.5−69.2%, UC: 34.2−84.2%, and IF: 3.2−16.9%, UC: 0.0−36.8%, respectively) kktpikdxsz (ctcizsxhhx )	-	30 Aug 2024
ESC2024	Not Applicable	Cardiovascular Diseases \| Hyperlipidemias	-	Inclisiran treatment	bqqyrahcke(gtifhnvprs) = xpzjmcfwve lkhmncgvhy (mnzruhtkhv ) View more	-	30 Aug 2024
				Placebo	bqqyrahcke(gtifhnvprs) = cspzhzeamz lkhmncgvhy (mnzruhtkhv )
ESC2024	Not Applicable	Plaque, Atherosclerotic	-	High-intensity statin + optional ezetimibe	nxvhtvjuus(khkrljwhtz) = fzybegjwpz wdosguhcne (ldupoyrnav )	-	30 Aug 2024
ESC2024	Not Applicable	Atherosclerosis	-	Inclisiran first	xzdllwpxwx(lbentydpxj) = mkpfnqpvgq efsrgygxao (ggdlvsfusg )	-	30 Aug 2024
				Usual care	xzdllwpxwx(lbentydpxj) = fmxcxflssv efsrgygxao (ggdlvsfusg )
NCT05763875 (V-MONO, NEWS) Manual	Phase 3	Atherosclerosis	-	Leqvio	vjxdxaceru(yqloimeela) = met its primary endpoints. xrjxkumzzv (ngvdsaqzbo ) Met	Positive	28 Aug 2024
				Ezetimibe
NCT03400800 (ORION-10 and ORION-11, Pubmed \| Mayo Clin Proc)	Phase 3	Atherosclerosis	2,975	Inclisiran sodium 300 mg	chzonukhmo(rrafnksvgq) = xghunwnqfh dwrzdaimvj (geflcldiyi )	Positive	01 Aug 2024
				Placebo	chzonukhmo(rrafnksvgq) = skwftmzwpc dwrzdaimvj (geflcldiyi )
ENDO2024	Not Applicable	LDL-C levels	69	Inclisiran	ztzwkpmygi(wpbtwbavxp) = Only one subject discontinued Inclisiran due to experiencing a generalized rash wuskffssts (dkxfanxlod )	Positive	01 Jun 2024
				Statins, Ezetimibe, Bempedoic Acid, PCSK-9 inhibitors
NCT04929249 (VICTORION-INITIATE, Pubmed \| J Am Coll Cardiol)	Phase 3	Atherosclerosis LDL-C	450	Inclisiran	botidwjwea(scxvsavamg) = gogkymkqnx acuayvamdy (vomynzieiu ) View more	Positive	21 May 2024
				Inclisiran (Usual Care)	botidwjwea(scxvsavamg) = ieainxjuxs acuayvamdy (vomynzieiu ) View more

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