NucleoSpace | China's RNAi Vessel Sets Sail Overseas

01

2024-1-7, Argo Biopharma announced that it had entered into two exclusive license cooperation agreements with Novastis regarding RNAi therapies.

Argo will receive an upfront payment of $185 million from Novastis and is eligible for potential option and milestone payments, as well as tiered royalties on commercial sales. The total potential value of the two deals could reach up to $4.165 billion.

The transaction projects discovered and developed using Argo's advanced RNA interference (RNAi) technology will strengthen and expand Novastis' RNAi portfolio in cardiovascular and metabolic diseases (CVM). Under the agreement, Argo will receive an upfront payment of $185 million (approximately RMB 1.29 billion) from Novastis and is eligible to receive potential option and milestone payments as well as tiered royalties on commercial sales. Novastis will obtain exclusive licenses for Phase I/IIa cardiovascular assets in Greater China, global exclusive licenses for Phase I cardiovascular assets, and the rights to compounds targeting up to two cardiovascular targets.

The first agreement indicates that Argo has granted Novastis an exclusive global license to develop and commercialize the Phase I project. The first agreement also includes a research collaboration, under which Novastis has obtained potential licenses for compounds targeting two additional cardiovascular disease treatment targets. In the second agreement, Argo granted Novastis an exclusive Greater China license to develop and commercialize a clinical-stage program in Phase 1/2a for cardiovascular disease treatment. The second deal is subject to approval under the Hart-Scott-Rodino Antitrust Improvements Act.

02

On January 3, 2024, Suzhou Ribo Life Science Co., Ltd. and Ribocure Pharmaceuticals AB (collectively referred to as "Ribo") joined hands with Boehringer Ingelheim of Germany to announce a collaboration to co-develop innovative small nucleic acid therapies for the treatment of non-alcoholic or metabolic dysfunction-associated steatohepatitis (NASH/MASH). This collaboration will closely integrate Ribo's leading expertise in early research and clinical development in the siRNA drug field with Boehringer Ingelheim’s commitment to improving the quality of life for patients with cardiovascular, renal, and metabolic diseases (CRM).

According to the terms of the collaboration, Rona Therapeutics will receive an upfront payment and is entitled to receive milestone payments based on the progress of clinical studies, regulatory submissions, and commercial success, as well as tiered royalties on product sales. The total value of the deal exceeds $2 billion.

03

2024-1-2, Voyager Therapeutics announced a collaboration with Novastis to jointly develop candidate gene therapies for Huntington's disease (HD) and spinal muscular atrophy (SMA).

Under the agreement, Novastis will pay a $100 million upfront payment, including the purchase of $20 million in newly issued equity in Voyager. Additionally, Voyager is eligible to receive up to $1.2 billion in preclinical, development, regulatory, and sales milestones, as well as tiered royalties on global net sales of drugs generated by Voyager's next-generation TRACER capsid discovery platform.

During the term of the agreement, Novartis will obtain: 1) Exclusive rights to SMA-related TRACER capsids and be responsible for all development and commercialization; 2) Global rights to the AAV-based HD gene therapy, with Voyager responsible for preclinical development and Novartis in charge of clinical development and commercialization of the HD program.

04

On January 5, 2024, Lion TCR announced a strategic collaboration agreement with MaxCyte to launch global cooperation, leveraging mRNA technology to develop TCR-T therapies for the treatment of solid tumors and virus-related diseases. This collaboration agreement enables Lion TCR to utilize MaxCyte’s Flow Electroporation® technology and ExPERT™ platform to accelerate its clinical programs and commercial applications.

According to the terms of the agreement, Lion TCR will obtain global non-exclusive clinical and commercial rights to MaxCyte's Flow Electroporation® technology and ExPERT™ platform, while MaxCyte will receive corresponding licensing fees and related project revenue. MaxCyte’s ExPERT™ portfolio represents the next generation of leading clinically validated mRNA electroporation technology, applied in complex and scalable cell engineering. By providing high transfection efficiency, seamless scalability, and advanced performance, the ExPERT™ platform delivers top-tier capabilities for next-generation biologics and cell therapies.

05

Recently, Vico Therapeutics announced the completion of a $60 million Series B financing round. This round was led by new investor Ackermans & van Haaren (AvH), with existing co-lead investors including Droia Ventures, EQT Life Sciences, and Kurma Partners, as well as previous investors Polaris Partners, Pureos Bioventures, and Eurazeo.

This financing will be used to support the company's overall operations, including advancing the ongoing VO659 Phase I/IIa multi-center, open-label basket trial. This trial aims to evaluate the safety and tolerability of multiple ascending doses of VO659 administered intrathecally in patients with mild to moderate SCA3, SCA1, and early HD, with the first patient dosed in April 2023. The funding will also help support the company’s further expansion of its product pipeline in other hereditary neurological disease areas.

06

On January 3, 2024, Sail Biomedicines (hereinafter referred to as "Sail"), a company under Flagship Pioneering, announced that it has received two grants from the Bill & Melinda Gates Foundation to advance Sail's pioneering circular RNA drug platform, Endless RNA™ (eRNA™), for the development of secreted monoclonal antibodies (mAb) and malaria vaccines based on circular RNA.

These agreements cover two funding programs. One supports the preclinical development of Sail's pioneering eRNA platform for a malaria vaccine product. Preclinical research data shows that the eRNA developed on this platform has longer expression duration and stronger immunogenicity compared to existing mRNA technologies. The development of this malaria vaccine is expected to become the first candidate vaccine product launched based on the eRNA platform; the second funding will support the development of an eRNA candidate drug encoding monoclonal antibodies, also for the prevention and treatment of malaria. The eRNA encoding secreted monoclonal antibodies, developed using this technology, can provide protection against the malaria pathogen and potentially more diseases in the future with higher persistence.

01

Recently, Professor Deng Yihui's team from Shenyang Pharmaceutical University published a research paper titled "Simultaneous dendritic cells targeting and effective endosomal escape enhance sialic acid-modified mRNA vaccine efficacy and reduce side effects" in the 364th issue of the journal *Journal of Controlled Release* in 2023.

The article points out that Dendritic Cells (DCs) are the only antigen-presenting cells (APCs) capable of activating naïve T cells, making them an important target for vaccine development. mRNA, with its high efficiency and self-adjuvant properties, shows great promise in the development of DC-targeted mRNA vaccines. However, since DC targeting typically requires ligand-receptor binding on the cell surface, the binding of various ligands to receptors often leads to the internalized material entering the lysosomal compartment. How to achieve both DC targeting and effective endosomal/lysosomal escape using a single nanocarrier is a critical issue currently facing the development of DC-targeted mRNA vaccines. Additionally, PEG lipids, which maintain the stability of lipid nanoparticles (LNPs), can mask targeting ligands, reducing the targeting efficiency of DCs.

In the article, the team developed a mRNA tumor vaccine co-modified with a sialic acid cholesterol derivative (SA-AE-AC-CH) and cleavable PEG lipid. This vaccine not only targets dendritic cells (DCs) but also achieves rapid endosomal escape within DCs, significantly increasing the expression of antigen proteins encoded by mRNA in DCs, enhancing the therapeutic efficacy of the vaccine, and reducing the side effects of the mRNA vaccine.

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