On July 17, 2023, DTx Pharma, a preclinical-stage biotech company, announced that it has been acquired by Novartis. It has a platform called “Fatty Acid Ligand Conjugated OligoNucleotide (FALCONTM)” that assists in the delivery of siRNA for RNAi therapeutics. On July 24, 2023, Roche paid Alnylam $310M to buy out a mid-stage cardiovascular drug candidate from Alnylam, which mainly focuses on siRNA for RNAi therapeutics. Today, we’ll briefly compare the two companies aiming at the same therapeutic method from different aspects.
- Company history and size
Alnylam Pharmaceuticals was founded in 2002 with its headquarters in Cambridge, Massachusetts, in the US. Only after about two years, the company successfully filed for an IPO. Now it has more than 1000 employees with a market cap of $24.91B.
DTx Pharma was founded in 2017 with its headquarters in San Diego, California, in the US. It finished Series B funding and was a privately traded company before its acquisition by Novartis. The total employee number is less than 50.
- Products and pipeline
Alnylam is the first and so far the only company to bring RNAi therapeutics to the market. It has already commercialized multiple products, including Onpattro (patisiran, 2018), Givlaari (givosiran, 2019), Oxlumo (lumasiran, 2020), Amvuttra (vutrisiran, 2022), and Leqvio (inclisiran, 2022). It has another 11 candidates in the clinical development pipeline. From the FDA approvals, it’s apparent that Alnylam has been working hard and also very successfully to push its drug candidates through the finish line of FDA approval in the past couple of years.
DTx hasn’t commercialized anything yet; however, it has four drug candidates in the pipeline in various stages from discovery to preclinical. With only five years of history, this achievement is very impressive.
- Therapeutic areas
Alnylam is currently focused on four therapeutic areas: genetic medicines, cardio-metabolic diseases, infectious diseases, and central nervous system (CNS) and ocular diseases, with genetic medicines being the primary focus. Patisiran, givosiran, and lumasiran are all for genetic medicines, and inclisiran is for cardio-metabolic diseases.
DTx is applying its FALCON platform to rare diseases like peripheral nervous system, muscular, and CNS disorders, and is planning to expand to additional therapeutic areas. The candidates in the pipeline are evenly distributed among the therapeutic areas.
- Delivery platform
Although the two companies differ in their therapeutic focus to some extent, the major difference is in their platform technology to deliver the siRNA into the targeted tissues/body parts.
Alnylam is using two platforms to deliver the siRNA. One is lipid nanoparticles (LNPs), and the other involves conjugates such as a sugar molecule or short lipid chain that is conjugated to the siRNA through a linker. LNPs are chemically synthesized with components like ionizable lipids, helper lipids, PEG, cholesterol, and nucleic acid payload. They are routed directly to their destination. But even with this, the actual percentage that is taken up by the target tissue is still very low. GalNAc Conjugates explore a sugar molecule, N-acetylgalactosamine, that can bind to the asialoglycoprotein receptor abundantly expressed by the target tissue, liver cells. And C16 conjugates use a C16 short lipid which increases membrane interaction with multiple cell types with its lipophilicity properties.
DTx’s FALCON platform utilizes fatty acid motifs that can bind to albumin in the bloodstream, thus preventing clearance by the kidney. By carefully choosing specific types and numbers of fatty acids to be linked to siRNA, it hopes to achieve specific targeting and enhance biodistribution.
But with any siRNA delivery platform, there are intrinsic challenges related to tissue specificity, immune response, and off-target effects that need to be further investigated.