Full Press Release Details
Christine Regan Lindenboom
(Investors and Media)
Alnylam Announces Partnership with
Roche to Co-Develop and Co-Commercialize Zilebesiran, an Investigational RNAi Therapeutic for the Treatment of Hypertension in Patients with High Cardiovascular Risk
Partnership Combines Alnylam s Leadership in RNAi Therapeutics with Roche s Proven Track Record of Successfully
Developing and Launching Innovative Medicines Worldwide
Zilebesiran Represents a Potentially Transformative Approach
to Reducing CV Morbidity and Mortality in Hypertension Patients at High CV Risk by Robustly and Durably Lowering Blood Pressure
Alnylam will Receive an Upfront Cash Payment of $310 Million and is Eligible to Receive Development, Regulatory, and Sales
Milestones, Including Substantial Near-Term Milestones, for a Potential Deal Value of up to $2.8 Billion, as well as an Equal Share of Profits and Losses in the United States and Royalties on Net Sales Outside the U.S.
Alnylam will Lead Joint Clinical Development Plan for First Indication, Including Cardiovascular Outcome Trial, with Development
Costs Shared Between the Companies
Alnylam and Roche will Co-Commercialize
Zilebesiran in the U.S., While Roche Obtains Exclusive Right to Commercialize Zilebesiran Outside the U.S.
Conference Call Today, Monday, July 24, at 08:00 a.m. ET to Discuss Collaboration
CAMBRIDGE, Mass. July 24, 2023
Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced it has entered into a strategic agreement with Roche to develop and commercialize zilebesiran, Alnylam s investigational RNAi therapeutic
for the treatment of hypertension, which is currently in Phase 2 of development. The partnership allows for a bold development plan with the goal of disrupting the hypertension treatment paradigm globally while advancing Alnylam s P5x25 strategy.
Roche provides Alnylam the benefits of an outstanding partner with a global
footprint and a proven track record of developing and commercializing novel therapies in complex markets. Roche has a proven history of innovating and commercializing medicines building upon their extensive global footprint which may potentially
enable zilebesiran to reach more patients with hypertension, a disease that affects more than 1.2 billion patients globally.
We are thrilled to announce this collaboration, as it combines Alnylam s proven track record in
RNAi therapeutics with Roche s global commercial reach, commitment to innovation and desire to transform the landscape for patients with severe cardiovascular diseases, said Yvonne Greenstreet MBChB, Chief Executive Officer
of Alnylam. With this collaboration, we now can develop zilebesiran in a more robust way, allowing us to have cardiovascular outcomes data in hand at launch to ensure results relevant not only for health authorities but also for access
and clinical practice in order to ultimately reach as many patients as possible.
We are excited to work together with Alnylam and leverage
our strong R&D capabilities, our leadership in cardiovascular diagnostics and our global commercial footprint to further develop and provide this promising therapy with
best-in-disease potential to patients, said Teresa Graham, CEO Roche Pharma. Throughout our history, we have redefined the standard of care across various
disease areas. Together with a strong partner like Alnylam, we are looking forward to making a significant impact for patients living with hypertension at high cardiovascular risk and potentially other cardiovascular indications.
In a Phase 1 study, zilebesiran, compared to placebo, was associated with dose-dependent reductions in serum angiotensinogen (AGT), achieving tonic
blood pressure control with consistent and durable blood pressure reduction throughout a 24-hour period, sustained up to six months after single doses of 200 mg. Zilebesiran also demonstrated an
acceptable safety profile supporting continued clinical development. The safety and efficacy of zilebesiran are being investigated in Alnylam s KARDIA Phase 2 clinical program either as a monotherapy
(KARDIA-1) or in combination with one of three standard-of-care antihypertensive medications
(KARDIA-2). Based on the positive Phase 1 data, zilebesiran could potentially be a best-in-disease treatment and provide
transformational benefit, especially for patients with hypertension at high cardiovascular risk. Zilebesiran also has the potential to improve adherence to treatment due to its possible biannual subcutaneous dosing regimen. In addition,
zilebesiran may be effective in additional potential cardiovascular indications with high unmet need.
Under the terms of the agreement, Alnylam will
receive an upfront cash payment of $310 million and is eligible to receive additional substantial near-term payments, including development milestone payments over the next few years, as well as regulatory and sales milestones, for a potential
deal value of up to $2.8 billion. In addition, Alnylam is entitled to an equal profit share in the U.S., where Alnylam and Roche will co-commercialize zilebesiran. Roche obtained the exclusive right to
commercialize zilebesiran outside the U.S. in exchange for low double digit royalties on net sales of zilebesiran outside of the U.S. Alnylam believes that this partnership will allow the companies to pursue a joint development plan and
commercialization approach that has the potential to unlock the full value of zilebesiran. Additionally, Alnylam will lead a joint clinical development plan for the first indication with Roche s participation, which includes a cardiovascular
outcomes trial prior to submission of zilebesiran for regulatory approval, with all development costs shared 40% by Alnylam and 60% by Roche. Roche may lead development for additional indications in the future.
Goldman Sachs & Co. LLC served as exclusive financial advisor to Alnylam.
Alnylam Conference Call Information
will discuss the new collaboration via conference call on Monday, July 24, 2023 at 8:00 am ET. To access the call, please register online at https://register.vevent.com/register/BIceae6347f7d14f5cb144ead1cf7cc974. Participants are
requested to register a minimum of 15 minutes before the start of the call. A replay of the call will be available two hours after the call and archived on the same web page for six months.
A live audio webcast of the call will be available on the Investors section of the Company s website at www.alnylam.com/events. An archived
webcast will be available on the Company s website approximately two hours after the event.
Zilebesiran is an investigational, subcutaneously administered RNAi therapeutic targeting angiotensinogen (AGT) in Phase 2 development for the treatment of
hypertension in high unmet need populations. AGT is the most upstream precursor in the Renin-Angiotensin-Aldosterone System (RAAS), a cascade which has a demonstrated role in blood pressure (BP) regulation and its inhibition has well-established
anti-hypertensive effects. Zilebesiran inhibits the synthesis of AGT in the liver, potentially leading to durable reductions in AGT protein and ultimately, in the vasoconstrictor angiotensin (Ang) II. Zilebesiran utilizes Alnylam s Enhanced
Stabilization Chemistry Plus (ESC+) GalNAc-conjugate technology, which enables subcutaneous dosing with increased selectivity and a wide therapeutic index. The safety and efficacy of zilebesiran have not been established or evaluated by the FDA, EMA
or any other health authority.
Hypertension is a complex multifactorial disease clinically defined by most major guidelines as a systolic blood pressure (SBP) of above 140 mm Hg and/or a
diastolic blood pressure (DBP) greater than 90 mm Hg, though AHA/ACC guidelines have a lower threshold of a SBP above 130 mm Hg and/or a DBP greater than 80 mm Hg. More than one billion people worldwide live with hypertension.1 In the U.S. alone, approximately 47 percent of adults live with hypertension, with more than half of patients on medication remaining above the blood pressure (BP) target level. Despite the
availability of anti-hypertensive medications, there remains a significant unmet medical need, especially given the poor rates of adherence to existing daily oral medications and daily peak and trough effects, resulting in inconsistent BP control
and an increased risk for stroke, heart attack and premature death.2 In particular, there are a number of high unmet need settings where novel approaches to hypertension warrant additional
development focus, including patients with poor medication adherence, difficult-to-treat and resistant hypertension, and in patients with high cardiovascular risk.
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 Twitter at @Alnylam, on LinkedIn, or on Instagram.
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, expectations regarding
Alnylam s aspiration to become a leading biotech company and the planned achievement of its Alnylam P5x25 strategy, Roche s participation in the
development and commercialization of zilebesiran, the potential for zilebesiran to disrupt the treatment paradigm in hypertension, Alnylam s expectations regarding the receipt of upfront cash, as well as potential development, regulatory and
sales milestones and royalties from Roche, Alnylam s ability to obtain approval for new commercial products or additional indications for its existing products, and Alnylam s projected commercial and financial performance, 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: the direct or indirect impact of
the COVID-19 global pandemic or any future pandemic on Alnylam s business, results of operations and financial condition and the effectiveness or timeliness of Alnylam s efforts to mitigate the
impact of the pandemic; 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
patisiran and vutrisiran; actions or advice of regulatory agencies and Alnylam s ability to obtain and maintain regulatory approval for its product candidates, including patisiran and 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; delays or interruptions in the
supply of resources needed to advance Alnylam s research and development programs, including as may arise from recent disruptions in the supply of non-human primates; obtaining, maintaining and protecting
intellectual property; Alnylam s ability to successfully expand the indication for ONPATTRO or 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 potential impact of a current government investigation and the risk of future government investigations; and unexpected
expenditures; as well as those risks more fully discussed in the Risk Factors filed with Alnylam s 2022 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.