– Launching on World Heart Day, Retired Professional Football Player Pete Shaw Shares How Symptoms Attributed to Football and Aging Led to a Delayed ATTR-CM Diagnosis –

– ‘Play by Play’ Uses Sports to Highlight the Strength of Earlier Diagnosis, TTR Silencing with AMVUTTRA, and Navigating ATTR-CM through Teamwork –

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced the launch of AMVUTTRA^® (vutrisiran) ‘Play by Play,’ a U.S. educational initiative featuring former professional athletes living with the cardiomyopathy of transthyretin-mediated amyloidosis (ATTR-CM) and the care teams who support them. Through personal stories and expert perspectives, ‘Play by Play’ aims to help people recognize the symptoms of ATTR-CM earlier and encourage informed conversations with healthcare professionals to help patients advocate for their diagnosis and treatment.

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Play by Play image collage featuring former professional athlete Pete Shaw holding a football, meeting with a doctor (Dr. Rajeev Mohan) alongside his partner (Kari Shaw), and spending time at home with family.

‘Play by Play’ kicks off with Pete Shaw, a former professional football player living with ATTR-CM, alongside his wife and caregiver, Kari, and one of his cardiologists, Rajeev Mohan, M.D. Together, they share Pete’s journey from experiencing symptoms that were mistakenly attributed to football or aging, to pursuing testing, receiving an ATTR-CM diagnosis, and ultimately starting treatment with AMVUTTRA, a transthyretin (TTR) silencer, as part of his game plan for ATTR-CM management.

Pete receives AMVUTTRA administered by his physician only four times per year via subcutaneous injection. AMVUTTRA demonstrates strength in RNAi-powered TTR silencing, delivering rapid knockdown of TTR at the source of disease to address the underlying cause of ATTR amyloidosis. AMVUTTRA is the only U.S. FDA-approved treatment for both ATTR-CM and the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults. The most common side effects associated with AMVUTTRA are pain in the arms or legs, pain in the joints, shortness of breath, and low vitamin A levels.

“The power of football is built play by play, and strength in silencing with AMVUTTRA is built on the same principle: making precise interventions where they matter,” said Tolga Tanguler, Chief Commercialization Officer at Alnylam. “Just as success on the field is built one play at a time, we believe that transformative impact in medicine starts with precisely targeting the drivers of disease. By harnessing RNAi to silence TTR at the source of disease, Alnylam is helping change what's possible for patients and their teams.”

Like many, Pete was not aware of the red flag symptoms associated with ATTR-CM and was accustomed to pushing through discomfort. As a result, he did not recognize that the changes he was experiencing could signal something more serious until Kari encouraged him to seek additional medical attention, helping set him on the path toward testing, diagnosis, and treatment.

“I spent my career learning how to read the field and react to what was happening around me. But when it came to my own health, I didn’t recognize that the symptoms I was experiencing could be something serious and progressive,” said Pete Shaw. “That’s why I’m sharing my story. If it helps even one person pay closer attention to changes in their health, ask questions, or start a conversation with their doctor, then sharing my experience is worth it.”

ATTR-CM is a serious, progressive disease caused by the buildup of misfolded TTR proteins in the heart. Recognizing ATTR-CM is often challenging because symptoms such as shortness of breath, fatigue, swelling in the lower legs, and irregular heart rhythms can resemble more common cardiovascular conditions. Awareness of family health history is also important because this disease can be hereditary. The gene variant Pete carries is more common in people of African descent.

‘Play by Play’ reflects the reality that navigating ATTR-CM takes a team by bringing together the perspectives of patients, caregivers, and healthcare professionals to explore the moments that shape the ATTR-CM journey. As part of Pete's care team, Dr. Mohan helped connect the clinical clues that led to his diagnosis and continues to play an important role in his disease management and treatment.

“Early diagnosis is one of the most important factors in the management of this disease,” said Rajeev Mohan, M.D., Director, Advanced Heart Failure Program, Scripps Clinic, and clinical cardiologist and heart failure specialist. “Pete’s journey underscores why awareness matters. An earlier diagnosis allows patients to have timely discussions about available treatment options and develop a management plan tailored to their needs.”

Please see the indications and important safety information below.

Hear Pete’s story and learn more about ATTR-CM and AMVUTTRA here. People experiencing possible symptoms should speak with a healthcare professional. Pete Shaw and Dr. Mohan have been compensated for their participation in this initiative.

Indications and Important Safety Information

Indications Approved by the U.S. FDA

AMVUTTRA^® (vutrisiran) is indicated for the treatment of the:

• cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality, cardiovascular hospitalizations and urgent heart failure visits.
• polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) 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

In a study of patients with hATTR-PN, 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%).

In a study of patients with ATTR-CM, no new safety issues were identified.

For additional information about AMVUTTRA, please see the full U.S. Prescribing Information (revised March 2025)

About AMVUTTRA^® (vutrisiran)

AMVUTTRA^® (vutrisiran) demonstrates strength in RNAi-powered transthyretin (TTR) silencing, delivering rapid knockdown of TTR at the source of disease to address the underlying cause of transthyretin amyloidosis (ATTR). In the HELIOS-B Phase 3 study, AMVUTTRA reduced the risk of all-cause mortality and recurrent CV events compared to placebo in the overall and monotherapy populations by 28.2% and 32.8%, respectively, through 36 months. It is the only TTR silencer approved for both the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) and cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in countries globally. AMVUTTRA is administered once quarterly via subcutaneous injection.

About Transthyretin Amyloidosis (ATTR)

Transthyretin amyloidosis (ATTR) is an underdiagnosed, rapidly progressive, debilitating, and fatal disease caused by pathogenic 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 wild-type ATTR (wtATTR), which occurs without a TTR gene variant. It is estimated that more than 500,000 people worldwide live with ATTR, with ~80% remaining undiagnosed.

About Alnylam Pharmaceuticals

Alnylam (Nasdaq: ALNY) is a leading global biopharmaceutical company and the pioneer of the RNA interference (RNAi) revolution. The Company is focused on developing transformative therapies with the potential to prevent, halt, or reverse disease. For more than two decades, Alnylam has advanced the Nobel-Prize-winning science of RNAi, delivering critical breakthroughs and six approved medicines. Alnylam has medicines available in more than 70 countries and a rapidly expanding and robust pipeline, in addition to consistently being recognized as an exceptional workplace and socially responsible organization. The Company is executing on its Alnylam 2030 strategy to accelerate innovation and scale impact to transform human health. For more information, please visit www.alnylam.com or follow Alnylam on X, LinkedIn, Facebook, Instagram, or YouTube.

Forward Looking Statements

This press release contains forward-looking statements. Forward-looking statements include statements regarding Alnylam’s expectations, beliefs, goals, plans or prospects, including, without limitation, statements regarding: the potential for early diagnosis of ATTR-CM to improve patient outcomes; the potential for ‘Pay by Play’ to help people recognize the symptoms of ATTR-CM earlier; the potential efficacy and safety of AMVUTTRA for the treatment of ATTR-CM; the ability of Alnylam to help change what’s possible for ATTR-CM patients and their teams; and Alnylam’s ability to achieve the goals in its Alnylam 2030 strategy, including to accelerate innovation and scale impact to transform human health. 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 2030 strategy; Alnylam’s ability to successfully launch, market and sell Alnylam’s approved products globally, including AMVUTTRA; 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; delays, interruptions or failures in the manufacture and supply of Alnylam’s marketed products or its product candidates; obtaining, maintaining and protecting intellectual property; Alnylam’s ability to manage its growth and operating expenses through disciplined investment in operations; 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, and Regeneron; the outcome of litigation and government investigations; the risk of future litigation and government investigations; and unexpected expenditures; as well as those risks and uncertainties more fully discussed in the “Risk Factors” filed with Alnylam’s most recent periodic report (Quarterly Report on Form 10-Q or Annual Report on Form 10-K) filed with the SEC and in its other SEC filings. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements.

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