Avidity Biosciences: The First AOC Biotech to Be Acquired, Valued at $5.8 Billion

On August 6, local time, the Financial Times cited sources as reporting that Novartis has been evaluating an acquisition of biotechnology company Avidity Biosciences (NASDAQ: RNA) and had expressed interest in pursuing a deal in recent weeks. Following this news, Avidity’s stock price surged 26.14% on Wednesday, reaching $48.26 per share, with its market capitalization hitting $5.817 billion (approximately RMB 41.7 billion).

People familiar with the matter told the Financial Times that discussions are still in their early stages and may not result in a deal. However, these sources added that an acquisition of Avidity Biosciences could command a premium. For Novartis, this potential transaction would be one of the largest under the leadership of CEO Vas Narasimhan.

Avidity Biosciences, founded in 2013 and listed on the NASDAQ in June 2020, possesses extensive expertise in oligonucleotide therapeutics, RNA process modulation, antibody engineering, conjugation, and drug delivery technologies, establishing itself as a pioneer in the development of Antibody-Oligonucleotide Conjugates (AOCs). AOCs, or Antibody-Oligonucleotide Conjugates, share a structural similarity with Antibody-Drug Conjugates (ADCs) and primarily consist of three components: an antibody for tissue targeting, a linker, and small nucleic acids serving as the payload.

However, compared with other conjugated drugs such as antibody-drug conjugates (ADCs), antibody-oligonucleotide conjugates (AOCs) utilize antibodies to deliver oligonucleotides to specific cells or tissues, thereby reducing the required therapeutic dosage and addressing the challenge of targeted oligonucleotide delivery. Compared with traditional small nucleic acid therapies, AOCs exhibit superior pharmacokinetic properties and more specific biodistribution. AOCs combine mature monoclonal antibody (mAb) technology with the precision and potency of oligonucleotide therapeutics; by conjugating different nucleic acid drugs to an antibody (or Fab fragment) targeting a single antigen, diverse diseases can be treated, highlighting their broad market potential across multiple therapeutic areas.

Novartis’ acquisition of Avidity targets, among other things, the latter’s proprietary AOC™ platform.This technology platform leverages targeted antibodies to precisely deliver oligonucleotides to specific tissues, overcoming the delivery bottlenecks associated with traditional RNA therapies and demonstrating significant application potential in the treatment of rare diseases. Specifically: regarding the antibody component, the platform enables the design of monoclonal antibodies with effector-silent functions, characterized by a robust safety profile, high specificity and affinity, and a long half-life; regarding the linker component, the platform employs non-cleavable linkers to enhance pipeline safety and durability while optimizing the oligonucleotide-to-antibody ratio; regarding the payload component, the platform is capable of delivering various nucleic acids, including siRNA and PMO, with a favorable safety profile, allowing for the modulation of specific disease processes through tailored oligonucleotides.

On the other hand, Novartis is also targeting Avidity’s three core rare disease products: Del-Disiran (AOC 1001), an AOC drug indicated for myotonic dystrophy type 1 (DM1); Del-Brax (AOC 1020), an AOC drug for the treatment of facioscapulohumeral muscular dystrophy (FSHD); and Del-Zota (AOC 1044), an AOC drug for the treatment of Duchenne muscular dystrophy (DMD).

Among Avidity’s pipeline, Del-Disiran is the most advanced candidate. It received FDA IND approval in August 2021, becoming the first antibody-oligonucleotide conjugate (AOC) drug to enter clinical development. Del-Disiran has been granted Breakthrough Therapy Designation, Orphan Drug Designation, and Fast Track Designation by the FDA, as well as Orphan Drug Designation by the European Medicines Agency (EMA). It is also the first investigational drug for myotonic dystrophy type 1 (DM1) to receive Orphan Drug Designation in Japan. On July 28 this year, Avidity announced that patient enrollment had been completed in HARBOR, its global Phase 3 clinical trial of Del-Disiran for DM1. As the first AOC drug to enter Phase 3 clinical trials globally, key data from this program are expected to be released in the second quarter of 2026.

Two other pipeline candidates also achieved key milestones this year: In June, Avidity announced that the accelerated approval regulatory pathway in the United States was open for Del-brax for the treatment of FSHD, and the global confirmatory Phase 3 FORWARD™ study for this candidate had been initiated. In July, Avidity announced that the FDA had granted Breakthrough Therapy designation to del-zota for the treatment of Duchenne muscular dystrophy in patients with exon 44 skipping (DMD44) mutations. Avidity plans to submit a Biologics License Application (BLA) for del-zota to the FDA by the end of this year.

According to a report released by the global market research firm 360i Research, the AOC market is projected to grow at a compound annual growth rate (CAGR) of 8.89%, reaching $5.26 billion by 2030. Although no commercialized products are currently available in this field, players have already entered various segments of the pharmaceutical industry chain, including multinational corporations (MNCs), biotechnology companies (Biotechs), and contract development and manufacturing organizations (CDMOs), gradually attracting both capital and technological resources.

In the MNC sector,In addition to Novartis mentioned earlier, Eli Lilly had already entered into a collaboration with Avidity Biosciences in 2019. This partnership leverages Avidity’s innovative technology platform to advance the discovery, development, and commercialization of a pipeline of potential new medicines, covering a broad range of therapeutic areas, including immunology as well as cardiovascular, hepatic, and muscular disorders.

In 2021, BMS, through its wholly owned subsidiary MyoKardia, entered into a collaboration with Avidity Biosciences. This R&D partnership focused on demonstrating the potential efficacy of Antibody-Oligonucleotide Conjugates (AOCs) in cardiac tissue, thereby validating the broad applicability of the AOC platform technology and its therapeutic potential in specific disease areas. In 2023, BMS further strengthened its collaboration with Avidity by directly executing a global license and research collaboration agreement. This agreement leverages Avidity’s platform technology to focus on the discovery, development, and commercialization of up to five cardiovascular antibody-oligonucleotide conjugate targets.

In 2024, Roche and Eli Lilly respectively disclosed their own AOC patents (WO2024017923A1 and WO2024036096), underscoring the strong interest and strategic layout of multinational corporations (MNCs) in the emerging AOC sector.

In the CDMO sector,This June, at the BioUSA conference in Boston, Samsung Biologics Vice President Kevin Sharp stated in an interview with reporters, “Leveraging our technological expertise in antibody-drug conjugates (ADCs), we will rapidly expand into the field of antibody-oligonucleotide conjugates (AOCs) and broaden our related CDMO services.” Notably, this marks the first time Samsung Biologics has officially listed AOCs as a business segment. Meanwhile, Lonza and WuXi Biologics have also established their presence in this area; the former has built dedicated AOC production lines, while the latter is committed to providing one-stop services ranging from drug design to manufacturing.

In the pharmaceutical industry,In addition to the AOC pioneer Avidity Biosciences, overseas companies such as Dyne Therapeutics, Denali Therapeutics, and Tallac Therapeutics, as well as domestic pharmaceutical companies including Jiajin Biologics, Shengshi Junlian, and HitGen (Chengdu), are actively positioning themselves in this therapeutic area. Among them, Dyne has a pipeline strategy similar to that of Avidity; its core asset, DYNE-101, is an antibody–oligonucleotide conjugate comprising an anti-TfR1 antibody linked to an antisense oligonucleotide (ASO), indicated for myotonic dystrophy type 1 (DM1). The company expects to submit a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) by the end of next year.

It is evident that over the next two years, multiple antibody-oligonucleotide conjugate (AOC) pipelines within the industry will transition from research and development to clinical stages, gradually completing the commercialization loop. The surge in AOC pipelines will open new avenues for the treatment of rare diseases.

References:

1. “AOC Race Heats Up! Samsung Biologics, WuXi AppTec, and Lonza Enter the Fray as First Drug Nears BLA Submission”

2. “MNCs’ 2024 New Star: ‘AOC’!”