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R&D Day 2023 Recap: Following the Science to Deliver on the Promise of RNAi Therapeutics
December 14, 2023
Alnylam was founded in 2002 by a group of distinguished life sciences leaders who believed in the vast potential of a newly discovered, natural process of silencing genes called RNA interference (RNAi). They assembled a talented team of researchers and encouraged them to harness the technology to treat disease by “following the science.”
That charge from leadership became ingrained in Alnylam’s culture, powering the company through the ups and downs of drug development, and more than 20 years later, we’re not only recognized as the global leader in RNAi therapeutics, but as a tireless scientific innovator when it comes to advancing the field of RNAi.
Our R&D (Research & Development) Day is an annual showcase of what’s new and next at Alnylam and in the RNAi RevolutionTM. During this year’s R&D Day held on December 13, 2023, our leadership discussed several exciting innovations and provided a look ahead at the rapid growth and evolution of our product pipeline. We invite you to read the press release and watch the full webcast replay.
Key Themes from Alnylam’s 2023 R&D Day:
Expanding research on common diseases
- Alnylam researchers shared information and updates about programs in clinical development across rare and common diseases, including transthyretin (ATTR) amyloidosis as well as hypertension, Alzheimer’s disease, type 2 diabetes mellitus (T2DM), and cancer.
There are now five approved RNAi therapeutics that were discovered at Alnylam, and by the end of 2025, we plan to file Investigational New Drug (IND) applications for at least nine new Alnylam-led RNAi programs, including five for targets expressed in the liver, two for the central nervous system (CNS), and one each for adipose tissue and muscle.
We made tremendous progress with our clinical portfolio in 2023, with the proof of concept for our central nervous system platform with ALN-APP, and demonstration of potent, tonic blood pressure control with zilebesiran. Promising Phase 1 data with ALN-TTRsc04 and ALN-KHK further demonstrate the strength of Alnylam’s R&D engine as we innovate and advance assets for rare and common diseases—including ATTR amyloidosis and type 2 diabetes mellitus. In addition, progress with ALN-BCAT demonstrates that Alnylam researchers continue to bring RNAi to new therapeutic areas such as oncology to help patients.” – Pushkal Garg, MD, Alnylam’s Chief Medical Officer and Executive Vice President of Development and Medical Affairs
The first few RNAi therapeutics were developed for rare diseases caused by mutations in a single gene. As confidence has grown in RNAi technology, our scientists and others in this field have expanded their focus to common diseases, which have complicated roots, with multiple genes and environmental factors driving them. Th expansion of RNAi technology to common diseases signals that the technology is poised to have a positive impact on the lives of millions of people around the world.
Discovering additional targets
- Alnylam scientists presented updates on new genetically validated targets for rare, specialty, and select common diseases including cholestatic liver diseases, a range of bleeding disorders, obesity, and T2DM.
We pursue genetically validated targets, significantly increasing the probability that our investigational therapeutics will work in patients. Our human genetics research has spurred a wave of exciting programs that are advancing toward clinical studies for a range of conditions.” – Paul Nioi, PhD, Vice President of Research & Head of Alnylam Human Genetics
Our investment in human genetics research continues to yield novel, genetically validated targets for a variety of diseases. When a target is genetically validated it means that there is direct evidence to suggest that changes in that target’s gene sequence are associated with either causing a particular disease or protecting an individual from developing that disease. After we identify a target, we can leverage our core RNAi platform technology and quickly move from a concept to an investigational therapeutic.
Innovating our core technology
- Alnylam scientists presented new preclinical findings demonstrating RNAi-mediated engagement of targets expressed in adipose tissue and muscle. We are progressing candidates that employ this new delivery technology toward the clinic.
- We shared preclinical data demonstrating systemic delivery of an RNAi therapeutic across the blood-brain barrier to the CNS. The results, while early, have the potential to broaden applications of RNAi therapeutics in the CNS.
We view the delivery of RNAi therapeutics to each new tissue as an engineering challenge. Building on our work in the liver and central nervous system, we aim to systematically unlock the entire body for therapeutic targets—tissue by tissue—to extend the applications of this transformative technology for millions of patients.” – Vasant Jadhav, PhD, Chief Technology Officer
The first RNAi therapeutics were delivered to the liver, an organ that was a prime target because liver cells, unlike most other cells, take up large molecules, and the key ingredient of any RNAi therapeutic is double-stranded RNA, which is a large molecule. Now we’re expanding beyond the liver. In 2023, we achieved the first human proof of concept of an investigational RNAi therapeutic in the CNS with a molecule administered intrathecally (directly into the CNS). And during R&D Day, we shared preclinical data demonstrating systemic delivery of an RNAi therapeutic across the blood-brain barrier, suggesting that subcutaneous injection might be possible for patients with neurological diseases in the future.
Alnylam researchers also presented promising preclinical data in adipose and muscle that indicate the potential for best-in-class delivery to these tissues. By the end of 2025, we plan to file two INDs for programs beyond the liver and CNS. All of this progress on delivery to new tissues complements efforts to optimize the design of RNAi therapeutics to enhance key features such as increased specificity, high potency, and long duration of activity, laying the foundation for infrequent dosing (utilizing our IKARIATM platform) as well as future therapeutics that engage multiple targets (utilizing our GEMENITM platform).
One thing has remained constant since I joined Alnylam 19 years ago: our commitment to following the science. We started the RNAi revolution in medicine by embracing this mantra, and we’ll continue to live by it as we strive to bring RNAi therapeutics to new tissues and diseases for millions of patients.” – Kevin Fitzgerald, PhD, Alnylam’s Chief Scientific Officer and Executive Vice President of Research and Early Development.
Learn more about our science as Alnylam grows and evolves while keeping R&D at its core.
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