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Alnylam and PeptiDream Enter into Collaboration Agreement to Discover and Develop Peptide-siRNA Conjugates for Targeted Delivery of RNAi Therapeutics to a Broader Range of Extrahepatic Tissues

− Agreement Combines PeptiDream’s Peptide Discovery Platform to Identify High Affinity Peptide Ligands with Alnylam’s Expertise in siRNA-Conjugate-Based Delivery and in Developing and Commercializing RNAi Therapeutics

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, and PeptiDream, Inc. (Tokyo Stock Exchange: 4587), the leading peptide-based drug discovery company with its proprietary Peptide Discovery Platform System (PDPS), announced today a license and collaboration agreement to discover and develop peptide-siRNA conjugates to create multiple opportunities to deliver RNAi therapeutics to tissues outside the liver. Through this collaboration, the companies will collaborate to select and optimize peptides for targeted delivery of small interfering RNA (siRNA) molecules to a wide range of cell types and tissues via specific interactions with receptors expressed on the target cells.

Under the terms of the alliance, Alnylam will select a set of receptors for PeptiDream’s peptide discovery platform. PeptiDream will select, optimize, and synthesize peptides for each receptor. Alnylam will then generate peptide-siRNA conjugates and perform in vitro and in vivo studies to support final peptide selection. The collaboration has the potential to yield multiple treatment opportunities by targeting disease causing mRNA transcripts in a wide variety of tissue types.

“Having solved delivery of RNAi therapeutics to the liver and made substantial preclinical progress on in vivo delivery to the CNS, eye, and lung, we are now adding to our suite of delivery technologies that have the potential to enable efficient delivery of siRNA to even broader tissue types throughout the human body,” said Kevin Fitzgerald, Ph.D., Chief Scientific Officer of Alnylam. “We are excited to enter into this collaborative research agreement with PeptiDream, an industry leader in the discovery and optimization of peptide ligands against a wide variety of receptors. Through this collaboration, we hope to identify robust ligand-receptor pairs for extrahepatic tissue delivery, similar to the GalNAc-ASGPR pair that we have pioneered for effective liver delivery.”

“We look forward to partnering with Alnylam to leverage our PDPS technology and peptide discovery capabilities to identify novel ligands against Alnylam selected target receptors that can facilitate delivery of drug payloads to a broad range of extrahepatic tissues,” said Patrick C. Reid Ph.D., President and Representative Director of PeptiDream. “This deal further expands on our strategy of using peptides to deliver a variety of therapeutic payloads (as peptide drug-conjugates) to disease cells/tissues in a targeted fashion. We hope this partnership will enable the creation of innovative peptide-siRNA conjugates in a variety of diseases and unlock many new therapeutic opportunities.”

Under the terms of the agreement, PeptiDream will receive an upfront payment from Alnylam as well as R&D funding over the term of the research collaboration, as provided in the agreement. PeptiDream may also receive payments based on the achievement of specified development, regulatory, and commercial milestones potentially totaling up to $2.2 billion (¥244 billion*1). In addition, PeptiDream is eligible to receive low-to-mid single digit royalties on sales on any such Alnylam products.

*1: USD/ JPY currency conversion rate: 110.9

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 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) is leading 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 genetic, cardio-metabolic, hepatic infectious, and central nervous system (CNS)/ocular diseases. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach for the treatment of a wide range of severe and debilitating diseases. Founded in 2002, Alnylam is delivering on a bold vision to turn scientific possibility into reality, with a robust RNAi therapeutics platform. Alnylam’s commercial RNAi therapeutic products are ONPATTRO® (patisiran), GIVLAARI® (givosiran), OXLUMO® (lumasiran), and Leqvio® (inclisiran) being developed and commercialized by Alnylam’s partner, Novartis. Alnylam has a deep pipeline of investigational medicines, including six 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.

About PeptiDream, Inc.

PeptiDream Inc. is a public (TSE: 4587) biopharmaceutical company founded in 2006 employing its proprietary Peptide Discovery Platform System (PDPS), a state-of-the-art highly versatile discovery platform which enables the production of highly diverse (trillions) non-standard peptide libraries with high efficiency, for the identification of highly potent and selective hit candidates, which then can be developed into peptide-based, small molecule-based or peptide-drug conjugate therapeutics. PeptiDream aspires to be a world leader in drug discovery and development to address unmet medical needs and improve the quality of life of patients worldwide. For further information, please visit https://www.peptidream.com.

Alnylam Forward Looking Statements

Various statements in this release concerning Alnylam’s expectations, plans, aspirations, and goals, including those related to the license and collaboration agreement with PeptiDream and the opportunity to discover and develop robust peptide-siRNA conjugates to create multiple opportunities to deliver RNAi therapeutics to a wide variety of tissue types outside the liver, the potential for payment of milestones and royalties to PeptiDream in the future, and the planned achievement of our “Alnylam P5x25” strategy, 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: 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 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 its product candidates; actions or advice of regulatory agencies and Alnylam’s ability to obtain and maintain regulatory approval for its product candidates, as well as favorable pricing and reimbursement; successfully launching, marketing and selling its 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 successfully expand the indication for ONPATTRO (or vutrisiran, if approved) 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 Novartis, Regeneron and Vir; the outcome of litigation; the risk of government investigations; and unexpected expenditures; as well as those risks more fully discussed in the “Risk Factors” filed with Alnylam's most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) 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.

Contacts

Alnylam Pharmaceuticals, Inc.

Christine Regan Lindenboom

(Investors and Media)

617-682-4340

Josh Brodsky

(Investors)

617-551-8276

PeptiDream, Inc.

Yuko Okimoto

IR & Public Affairs

y-okimoto@peptidream.com

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