– Company Expects to Initiate a Phase 1/2 Study for ALN-KHK in Early 2023, with Initial Results Expected in Late 2023 –

CAMBRIDGE, MA, USA I December 21, 2022 I Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi (RNA interference) therapeutics company, announced today that the Company has submitted a Clinical Trial Authorization (CTA) application to Health Canada to initiate a Phase 1/2 study of ALN-KHK, an investigational RNAi therapeutic targeting ketohexokinase (KHK) for the treatment of Type 2 diabetes mellitus (T2DM). Pending regulatory authority and ethic committee approvals, the Company plans to begin enrollment in a Phase 1/2 study in healthy overweight to obese volunteers and obese patients with T2DM in early 2023, and expects to report initial human data in late 2023.

“We are excited to advance ALN-KHK to the clinic as our first RNAi therapeutic to address the unmet medical need in Type 2 diabetes mellitus and potentially other metabolic disorders,” said Neil Wallace, Program Leader for the ALN-KHK program at Alnylam. “Increased dietary fructose consumption, largely resulting from use of high-fructose corn syrup as a sweetener, is believed to contribute to the growing pandemic of obesity. Obesity is a significant risk factor for both T2DM and fatty liver disease. Fructose itself predisposes to fatty liver disease and thus, in the context of T2DM, aggravates insulin resistance. We believe targeting ketohexokinase, also known as fructokinase, the first enzyme in the pathway of fructose metabolism, is a novel therapeutic approach to reduce fatty acid synthesis and insulin resistance, with the potential to improve overall glycemic control in individuals with T2DM.”

ALN-KHK is a wholly-owned asset in the Alnylam clinical development portfolio.

ALN-KHK is an investigational, subcutaneously administered RNAi therapeutic targeting ketohexokinase for the treatment of Type 2 diabetes mellitus (T2DM). ALN-KHK 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 ALN-KHK have not been evaluated by the FDA, EMA, Health Canada, or any other health authority.

About Type 2 Diabetes Mellitus
Type 2 Diabetes Mellitus (T2DM) is a global disease affecting more than 6% of the world’s population. Its incidence and prevalence rates are believed to be increasing worldwide with estimates of more than 450 million affected. The prevalence of diabetes is expected to reach 55 million within the US by 2030. Management of T2DM is aimed at achieving a target hemoglobin A1c levels (a measure of blood sugar) of less than 7%. Typically diet and exercise are recommended with the aim of achieving weight loss; this is rarely successful. Despite a number of treatment options, many patients do not reach adequate blood sugar control. There is an unmet need for a treatment that can produce sufficient glycemic control while providing simpler dosing administration and longer dosing intervals that could improve treatment compliance, thereby reducing disease complications and overall mortality.

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 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 20 years ago, 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), GIVLAARI® (givosiran), OXLUMO® (lumasiran), AMVUTTRA® (vutrisiran) 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.

SOURCE: Alnylam Pharmaceuticals