Patisiran sodium

Sep 09, 2025 CAMBRIDGE, Mass. --(BUSINESS WIRE)--Sep. 9, 2025-- Alnylam Pharmaceuticals, Inc. (“Alnylam”) (Nasdaq: ALNY), the leading RNAi therapeutics company, announced today the pricing of its previously announced private offering of $575 million aggregate principal amount of 0.00% convertible senior notes due 2028 (the “notes”) to persons reasonably believed to be qualified institutional buyers pursuant to Rule 144A under the Securities Act of 1933, as amended (the “Securities Act”). The size of the offering was increased from the previously announced offering of $500 million aggregate principal amount of notes. In addition, Alnylam granted the initial purchasers of the notes an option to purchase, for settlement within a 13-day period beginning on, and including, the date on which the notes are first issued, up to an additional $86.25 million aggregate principal amount of the notes. The offering is expected to close on September 12, 2025 , subject to customary closing conditions. The notes will be senior, unsecured obligations of Alnylam and will not bear regular interest, and the principal amount of the notes will not accrete. The notes will mature on September 15, 2028 , unless earlier converted, redeemed or repurchased. Before June 15, 2028 , noteholders will have the right to convert their notes in certain circumstances and during specified periods. From and after June 15, 2028 , noteholders may convert their notes at any time at their election until the close of business on the second scheduled trading day immediately before the maturity date. Alnylam will settle conversions by paying or delivering, as applicable, cash, shares of its common stock, par value $0.01 per share (“common stock”), or a combination of cash and shares of its common stock, at Alnylam’s election. The initial conversion rate is 1.4923 shares of common stock per $1,000 principal amount of the notes, which represents an initial conversion price of approximately $670.11 per share of Alnylam’s common stock. The initial conversion price represents a premium of approximately 40% above the U.S. composite volume weighted average price of Alnylam's common stock from 12:30 p.m. through 4:00 p.m. Eastern Daylight Time on September 9, 2025 , which was $478.6327 per share. The conversion rate and conversion price will be subject to adjustment upon the occurrence of certain events. The notes will be redeemable, in whole or in part (subject to certain limitations), for cash at Alnylam’s option at any time, and from time to time, on or after September 20, 2027 and on or before the 21st scheduled trading day immediately preceding the maturity date, if the last reported sale price per share of Alnylam’s common stock equals or exceeds 130% of the conversion price for a specified period of time. The redemption price will be equal to the principal amount of the notes to be redeemed, plus accrued and unpaid special interest, if any, to, but excluding, the redemption date. In connection with the pricing of the notes, Alnylam entered into privately negotiated capped call transactions with certain of the initial purchasers or their respective affiliates and certain other financial institutions (the “option counterparties”). The capped call transactions are expected generally to reduce potential dilution to Alnylam’s common stock upon conversion of any notes and/or offset any potential cash payments Alnylam is required to make in excess of the principal amount of converted notes, as the case may be, with such reduction and/or offset subject to a cap. The cap price of the capped call transactions will initially be approximately $837.61 per share of Alnylam’s common stock, which represents a premium of approximately 75% over the U.S. composite volume weighted average price of Alnylam’s common stock from 12:30 p.m. through 4:00 p.m. Eastern Daylight Time on September 9, 2025 . Alnylam has been advised that, in connection with establishing their initial hedges of the capped call transactions, the option counterparties or their respective affiliates expect to purchase shares of Alnylam’s common stock and/or enter into various derivative transactions with respect to Alnylam’s common stock concurrently with or shortly after the pricing of the notes. This activity could increase (or reduce the size of any decrease in) the market price of Alnylam’s common stock or the notes at that time. In addition, the option counterparties and/or their respective affiliates may modify their hedge positions by entering into or unwinding various derivatives with respect to Alnylam’s common stock and/or purchasing or selling Alnylam’s common stock or other securities of Alnylam in secondary market transactions from time to time prior to the maturity of the notes (and are likely to do so during any observation period related to a conversion of notes or following certain repurchases or redemptions of the notes). This activity could cause or avoid an increase or a decrease in the market price of Alnylam’s common stock or the notes, which could affect the ability of holders to convert the notes and, to the extent the activity occurs following conversion or during any observation period related to a conversion of notes, it could affect the amount and value of the consideration that holders will receive upon conversion of such notes. Alnylam estimates that the net proceeds from the offering of the notes will be approximately $561.6 million (or approximately $645.9 million if the initial purchasers exercise their option to purchase additional notes in full), after deducting the initial purchasers’ discounts and estimated offering expenses payable by Alnylam . Alnylam intends to use approximately $30.7 million of the net proceeds from the offering to pay the cost of the capped call transactions. If the initial purchasers exercise their option to purchase additional notes, Alnylam expects to use a portion of the net proceeds from the sale of the additional notes to enter into additional capped call transactions. In addition, Alnylam intends to use the remainder of the net proceeds from the offering, together with cash on hand, to repurchase for cash approximately $637.8 million aggregate principal amount of Alnylam’s 1.00% convertible senior notes due 2027 (the “existing notes”) through privately negotiated transactions entered into concurrently with the pricing of the notes. Concurrently with the pricing of the notes, Alnylam entered into privately negotiated transactions (the “note repurchase transactions”) with certain holders of the existing notes to repurchase for cash approximately $637.8 million aggregate principal amount of the existing notes for a total repurchase cost (including accrued and unpaid interest) of approximately $1,105.8 million . The terms of the note repurchase transactions were individually negotiated with certain holders of the existing notes and depended on a variety of factors, including the market price of Alnylam’s common stock and the trading price of the existing notes at the time of the note repurchase transactions. This press release is not an offer to repurchase the existing notes, and the offering of the notes is not contingent upon the repurchase of the existing notes. In connection with the note repurchase transactions, Alnylam expects that holders of the existing notes who have agreed to have their existing notes repurchased and who have hedged their equity price risk with respect to such existing notes (the “hedged holders”) will unwind all or part of their hedge positions by buying Alnylam’s common stock and/or entering into or unwinding various derivative transactions with respect to Alnylam’s common stock. The amount of Alnylam’s common stock to be purchased by the hedged holders or the notional number of shares of Alnylam’s common stock underlying such derivative transactions may be substantial in relation to the historic average daily trading volume of Alnylam’s common stock. This activity by the hedged holders could increase (or reduce the size of any decrease in) the market price of Alnylam’s common stock, including concurrently with the pricing of the notes, resulting in a higher effective conversion price of the notes. Alnylam cannot predict the magnitude of such market activity or the overall effect it will have on the price of the notes or Alnylam’s common stock and the corresponding effect on the initial conversion price of the notes. The notes were offered only to persons reasonably believed to be qualified institutional buyers pursuant to Rule 144A under the Securities Act. The offer and sale of the notes and any shares of common stock issuable upon conversion of the notes have not been, and will not be, registered under the Securities Act or any other securities laws, and the notes and any such shares cannot be offered or sold absent registration or except pursuant to an applicable exemption from, or in a transaction not subject to, the registration requirements of the Securities Act and any other applicable securities laws. This press release does not constitute an offer to sell, or the solicitation of an offer to buy, the notes or any shares of common stock issuable upon conversion of the notes, nor will there be any sale of the notes or any such shares, in any state or other jurisdiction in which such offer, sale or solicitation would be unlawful. 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 include AMVUTTRA® (vutrisiran), ONPATTRO® (patisiran), GIVLAARI® (givosiran), and OXLUMO® (lumasiran), which are being developed and commercialized by Alnylam , and Leqvio® (inclisiran) and Qfitlia™ (fitusiran), which are being developed and commercialized by Alnylam’s partners, Novartis and Sanofi, respectively. 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. Alnylam Forward Looking Statements Various statements in this release concerning Alnylam’s future expectations, plans and prospects, including, without limitation, statements regarding: whether Alnylam will issue the notes; whether the note repurchase transactions will settle; the anticipated use of the net proceeds from the offering; expectations regarding the effect of the capped call transactions; expectations regarding actions of the hedged holders, the option counterparties and their respective affiliates; and whether the capped call transactions will become effective, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. 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; 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; delays, interruptions or failures in the manufacture and supply of its product candidates or its marketed products; obtaining, maintaining and protecting intellectual property; 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; the outcome of litigation; the potential risk of future government investigations; and unexpected expenditures; 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 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. View source version on businesswire.com: https://www.businesswire.com/news/home/20250909474901/en/ Alnylam Pharmaceuticals, Inc. Christine Akinc (Investors and Media) +1-617-682-4340 Josh Brodsky (Investors) +1-617-551-8276 Source: Alnylam Pharmaceuticals, Inc.

iStock, Deagreez In the wake of multiple patient deaths from liver injuries related to Sarepta Therapeutics’ AAV gene therapy platform, some in the sector are looking for ways to improve the current technology, while others are eager to move on. If a patient is a good candidate to receive a gene therapy, delivering it using an adeno-associated virus (AAV) is a natural choice. AAVs are the current standard bearer for delivering functional genes to patients with genetic diseases. Duchenne muscular dystrophy (DMD)—a lethal muscle disease caused by mutations in the dystrophin gene—is a natural candidate for gene therapy. But Sarepta Therapeutics’ recent, well-publicized saga has rocked the gene therapy space. Within the last few months, two patients with DMD who received the company’s AAV gene therapy Elevidys died from liver injury, as did a patient in a Phase I clinical trial for the company’s limb-girdle muscular dystrophy gene therapy SRP-9004, which uses the same underlying platform technology as Elevidys. The issue with AAVs in these cases is a problem for just about anything that enters the bloodstream: they accumulate in the liver. That’s not a problem unique to this technology, but its significance lies in one of the major drawbacks of using AAVs: their immunogenicity. “Everything goes to the liver, not just viruses,” Nitin Joshi, a bioengineer and assistant professor at Harvard Medical School whose lab develops gene therapies for a variety of disorders, told BioSpace . “This is an issue for all drugs, including small molecules.” It’s a bigger problem with AAVs, however, because viruses can raise a response from the immune system, causing damaging effects like cytokine storm, he explained. AAVs were discovered in 1965 and quickly recognized for their ability to deliver DNA into cells. In 1984 , scientists demonstrated a landmark proof of concept: AAVs could deliver a gene to a mammalian cell. Novartis’ Luxturna , which in 2017 became the first-ever FDA-approved gene therapy, for a rare form of inherited vision loss, is delivered using an AAV vector. Now, with a spate of high-pro on its docket, the gene therapy space is asking itself questions about AAV, its old reliable workhorse. Even before the recent deaths connected to Elevidys, thirteen deaths were linked to AAV gene therapy between 2021 and 2024, according to an article published by the Norn Group. After news of the third death linked to Sarepta’s platform broke, fears for AAV’s future exploded on social media. Zhonghao (John) Liu, founder and CSO at YOLO Immune, compared the situation to the death in the 1990s of Jesse Gelsinger after being injected with an experimental gene therapy using an adeno-virus vector to treat his genetic disease of urea cycle disorder. The FDA stopped all ongoing gene therapy trials at that time, Liu wrote in a LinkedIn post in late July. “Today’s event may become the second turning point for the whole gene therapy field! Chilling Winter Is Coming!” But AAV’s demise may have been greatly exaggerated. “AAVs will have value in the long run,” Emil Kakkis, CEO of Ultragenyx, told BioSpace. A Real Sponge for Drugs AAVs are popular—even among the suite of other viruses available to deliver drugs, like retroviruses—for a very specific reason: they can deliver DNA directly to the nucleus of non-dividing cells. That separates them from retroviruses, which can only target dividing cells, and lentiviruses, which can target non-dividing cells but struggle to deliver DNA to the nucleus, where it can be expressed stably. That opens up the virus’ tissue-targeting abilities far beyond other viral and nonviral platforms. Sarepta, Elevidys and the liver injuries sustained by patients taking the drug have not come under the spotlight because patients with DMD are especially susceptible to liver side effects. In contrast, myotubular myopathy, another genetic condition that produces severe muscle weakness, does cause liver problems on its own. In 2020 , two patients taking an experimental AAV-delivered therapy for myotubular myopathy made by Audentes Therapeutics (now a part of Astellas Pharma) died of liver injury. “But unlike myotubular myopathy, DMD patients don’t have underlying liver disease usually, and [it] also seems like liver failure in the three Sarepta cases are more consistent with AAV-associated immune reaction,” Joshi told BioSpace in a follow-up email. Instead, in DMD, the problem is that AAVs accumulate exceptionally well in the liver but are difficult to target anywhere else. Dystrophin is mutated in the muscle, which AAVs do not target particularly well. Also, since muscle is distributed throughout the body, a replacement gene needs to be delivered systemically as opposed to locally. Because muscle is such a tricky tissue to target, gene therapies for DMD need to use AAV doses several orders of magnitude higher than those for a genetic disease related to the liver, Kakkis explained. That is why DMD patients are experiencing liver injuries: they are simply receiving much, much more virus than patients with other conditions, he said. “For liver conditions, you don’t need a higher dose,” Kakkis said. “For other places you need to increase the dose.” This also comes down to issues with manufacturing AAVs. It is difficult to prepare fully potent AAVs where every single capsid contains a therapeutic gene. According to Kakkis, a therapeutic dose of a gene therapy’s DNA can be made up of up to 50% empty viruses, meaning patients are getting double the dose of virus that they actually need. However, Sarepta’s struggles do not mean the end of AAVs. A bevy of companies, including KBI Biopharma and BioChromatographix , in addition to academic scientists, are actively researching methods —like ultracentrifugation and particular kinds of chromatography—to separate out empty capsids in an AAV preparation, potentially lowering the effective dose for gene therapies like Elevidys. Another popular fix for AAV’s struggles with liver injuries is to give patients steroids along with their gene therapy in an attempt to muffle an immune reaction to the virus. According to Kakkis, this has long been a common approach for gene therapy companies, and one Ultragenyx is employing in its Sanfilippo syndrome program. Ultragenyx received a Complete Response Letter from the FDA last month for its Sanfillippo candidate UX111, also an AAV-based gene therapy. The regulator cited manufacturing concerns, but Kakkis remained confident in the company’s viral technology. “We have been testing AAVs in four different conditions with no safety issues. We look at AAVs as a very safe format and we’re invested in it,” he said. “With continued improvement in AAV technology, it’ll be around for a very long time.” Beyond AAV While some in the gene therapy industry look to fine-tune AAVs for greater safety, others are charting a course away from the old stalwart. One of these individuals is Harvard’s Joshi. “It’s the holy grail [of gene therapies] to move away from viral vectors,” he said. “The field agrees we need new materials with the ability to transfect cells.” Other gene delivery platforms, particularly lipid nanoparticles (LNPs), have come to the fore as alternative methods. LNPs have the simple advantage of not being a virus and therefore having much lower immunogenicity, avoiding the liver injury complications of AAV-based therapies. While not a gene therapy, Moderna’s mRNA-based COVID-19 vaccine Spikevax uses LNPs to deliver its payload. It sidesteps a key issue with LNPs that echo AAVs’ issues: they’re difficult to target anywhere but the liver. Moderna doesn’t have that problem because its vaccine can be delivered into the bloodstream without much targeting and still raise an immune response. It’s not just vaccines that are leveraging LNPs. Alnylam’s Onpattro , an siRNA therapy for hereditary amyloidosis, uses an LNP vehicle to deliver its payload. However, this is again a liver-directed condition, so targeting is not an issue. Kakkis reiterated that AAVs are here to stay, even if further improvements in dosing and immunogenicity are needed. “I look at Sarepta’s drug as a first-generation drug. What Sarepta’s done is open the door to other improvements,” he said, pointing to companies like Solid Bioscience that are developing next-generation delivery systems. “We have been testing AAVs in different conditions [like Sanfilippo syndrome and Wilson disease] with no safety issues,” he said. “I think AAVs are a very safe way to deliver DNA to the liver. With continued improvement in AAV technology, it’ll be around for a very long time.” And the stakes for patients, especially those with DMD, are extremely high. “There are kids living and dying today, so it’s now or never, not three to five years from now on. In that setting, the treatment has value.”