Sirnaomics Announces Successful Completion of Phase I Clinical Trial for STP707, a Novel siRNA Therapeutic for Advanced Solid Tumors

02

On 2023-8-28, Pfizer and BioNTech filed a request with the U.S. government court on 2023-8-28 to invalidate two of Moderna's COVID-19 vaccine technology patents. Moderna has accused the two companies of patent infringement.

Pfizer and BioNTech stated that the two patents are "unimaginably broad," covering "basic ideas that were already known" prior to their invention date in 2015. In their patent application, Pfizer and BioNTech noted that scientists discovered as early as 1990 that mRNA could be used in vaccines. The two companies argued that Moderna’s patents are invalid based on independent patent applications from as early as 2004 and other publications.

Moreover, Pfizer stated in a declaration that the vaccine developed by Pfizer and BioNTech is "based on BioNTech's proprietary mRNA technology and co-developed by BioNTech and Pfizer," and they are confident in their intellectual property.

03

Avidity Biosciences, dedicated to the development of Antibody Oligonucleotide Conjugate (AOC) drugs, announced that it will present two posters at the Myotonic Dystrophy Foundation Annual Conference, held from September 7, 2023, to September 9, 2023. The titles of the two posters are: "AOC 1001 Demonstrates DMPK Reduction and Splicing Improvement in a Phase Ⅰ/Ⅱ Study for Type 1 Myotonic Dystrophy (DM1) (MARINATM)" and "Primary Data Analysis of the Phase Ⅰ/Ⅱ Clinical Trial MARINATM Evaluating AOC 1001 in Adult Patients with Type 1 Myotonic Dystrophy."

Among them, Avidity is revolutionizing the RNA field through its proprietary AOC, which aims to combine the specificity of monoclonal antibodies with the precision of oligonucleotide therapies to address targets and diseases that were previously unreachable by existing RNA therapies. Leveraging its proprietary AOC platform, Avidity has successfully achieved RNA targeted delivery to muscles for the first time and is at the forefront of clinical development programs for three rare muscle diseases: Myotonic Dystrophy Type 1 (DM1), Duchenne Muscular Dystrophy (DMD), and Facioscapulohumeral Muscular Dystrophy (FSHD).

04

Recently, Alnylam persisted in its patent litigation against Moderna's COVID-19 vaccine. In a recent statement, Alnylam indicated that following a ruling on certain patent claims in the Federal Court of Delaware, both Alnylam and Moderna agreed to a final judgment of non-infringement; however, Alnylam committed to appealing the decision.

Specifically, Alnylam accused Moderna of using its lipid nanoparticle (LNP) delivery technology, which was developed by the biotech company for its RNAi drug Onpattro, a treatment for the rare disease hereditary transthyretin-mediated amyloidosis.

05

2023-9-1, Innovac Therapeutics, a biotechnology company dedicated to researching and developing innovative mRNA vaccines and therapies, announced the completion of a $18 million Pre-A round of financing. The investors include Licheng Capital, Yuanjing Capital, Yinglian Health Fund, TG Sino-Dragon Fund, and other well-known institutions in the industry.

The proceeds from this round of financing will be used to develop an mRNA technology platform with independent intellectual property rights and build production capacity to advance pipeline projects to the clinical stage. This financing round, participated in by multiple well-known investment institutions, represents the industry's recognition and support of Innovac Therapeutics' platform technology, mission, and vision.

06

On September 1, 2023, EOC Pharma Group and NPD jointly announced the signing of a strategic cooperation agreement to deepen collaboration in the research and development of small nucleic acid drugs in the cardiovascular field. Under the agreement, NPD exclusively authorized EOC Pharma Group to develop, manufacture, and commercialize two siRNA drugs targeting ANGPTL3 and Lp(a) in Greater China and Southeast Asia. EOC Pharma Group will pay NPD an upfront payment, milestone payments, and royalties on future product sales after commercialization.

07

On August 26, 2023, 3D Medicines Inc. and Shanghai Yisi Biopharmaceutical Technology Co., Ltd. reached a collaborative development agreement to jointly focus on the next generation of mRNA cancer vaccines, providing more precise treatment options for cancer patients. In this joint development collaboration, 3D Medicines and Yisi Biopharma will co-develop the next generation of cancer vaccine products based on mRNA delivery design, offering more treatment methods to help cancer patients live longer and better lives.

Among them, 3D Medicines has global experience in innovative drug development and commercialization. Its first commercial product, Envada® (Envida®), has achieved cumulative sales of over 1 billion RMB. The company’s first cancer vaccine has entered Phase III clinical trials globally; currently, two peptide-based cancer vaccines are under development, with the first one, 3D189, already in Phase III clinical trials worldwide, and the trial among the Chinese population is proceeding smoothly. This collaboration will enrich 3D Medicines' pipeline of cancer vaccines, enabling peptide-based cancer vaccines and mRNA cancer vaccines to advance side by side, strengthening its position in the field of cancer chronic disease management.

The team at Shanghai Yisi Biopharmaceutical Technology Co., Ltd. has extensive experience in mRNA vaccine research, development, and process scaling. They possess both linear and self-amplifying RNA platforms and have independently developed an mRNA sequence optimization platform capable of generating highly efficient and stable mRNA molecules. Their AI-driven antigen design platform can more precisely activate the immune system.

01

Professor Daniel Anderson from MIT and Associate Professor Wen Xue from the University of Massachusetts published a correspondence titled "Combinatorial design of nanoparticles for pulmonary mRNA delivery and genome editing" in Nature Biotechnology.

Although non-viral vector-based gene therapies have broad applications in treating lung diseases, they are still limited by the challenge of delivery. In this communication, the authors utilized a high-throughput platform to synthesize and screen a combinatorial library of biodegradable ionizable lipids to construct inhalable delivery vehicles for mRNA and CRISPR-Cas9 gene editing systems. The novel lipid nanoparticles (LNPs) obtained through screening and characterization are suitable for repeated intratracheal administration, enabling highly efficient gene editing in lung epithelial cells, and opening new avenues for the gene therapy of congenital lung diseases.

First, the author designed a three-component reaction system (3-CR), in which the two ends of the nitro ricinoleic acid acrylate (NRA) linker are connected to fatty alcohol (lipid tail) and head groups containing primary, secondary, or tertiary amines, respectively. The positive charge carried by the head group facilitates the interaction between nanoparticles and negatively charged mRNA, and also helps prevent mRNA from being engulfed by cells after entering them. Meanwhile, the lipid tail structure assists particles in passing through cell membranes. Compared with the traditional two-component reaction that directly connects amine-containing head groups with lipid tail groups, this 3-CR system simplifies the cumbersome synthesis process, increases the diversity of lipid structures, and rapidly generates a combinatory library of structurally diverse biodegradable ionizable lipids.

The author synthesized a compound library containing 720 new lipid compositions, which were constructed by connecting 10 different lipid tails and 72 different head groups through an NRA linker. Overall, the study synthesized and evaluated 720 biodegradable ionizable lipids. It was identified that RCB-4-8 LNP is an efficient non-viral delivery system capable of achieving gene editing in the lungs, opening new avenues for treating congenital lung diseases.

02

Professors Qianqian Ni and Xiaoyuan Chen from the Yong Loo Lin School of Medicine at the National University of Singapore published a communication titled "Activatable NIR-II Photothermal Lipid Nanoparticles for Improved Messenger RNA Delivery" in Angew. Chem. Int. Ed.

The release of RNA after liposome endocytosis into cells remains a core issue limiting high protein expression in mRNA therapy. In this paper, the authors developed second near-infrared (NIR-II) lipid nanoparticles (LNPs) containing pH-dependent NIR-II dye-conjugated lipids (Cy-lipid), enhancing mRNA delivery efficiency through a Stimuli-Responsive Endosomal Escape Delivery (SPEED) strategy using photothermal promotion. In the acidic endosomal microenvironment, Cy-lipid becomes protonated and activates NIR-II absorption under 1064 nm laser irradiation, performing photothermal transduction. Subsequently, the heat induces morphological changes in LNPs, triggering rapid endosomal escape of NIR-II LNPs, which increases the corresponding mRNA translational capacity by approximately threefold.

Development of a new and efficient endosomal escape pathway to enhance mRNA translation is of great significance for improving protein yield. Therefore, researchers have attempted to introduce light-controlled strategies to regulate the escape process after endocytosis. Essentially, these light-controlled strategies rely on nanoscale structural changes induced by photosensitive molecules, thereby achieving highly efficient release. Currently reported photosensitive groups, such as o-nitrobenzyl and azobenzene, are located in the first infrared window with poor tissue penetration capability. In contrast, photons in the second near-infrared (NIR-II) region exhibit significant advantages, with a penetration depth of up to 5-20 mm. Thus, in this paper, the authors developed pH-responsive NIR-II dye-conjugated liposomes (Cy-lipid), which can respond to a 1064 nm laser. Remote phototriggering of NIR-II LNPs containing Cy-lipid via the SPEED strategy can improve the translation efficiency of mRNAs encoding eGFP and firefly luciferase. Within the pH range of 7.4 to 5.0, the absorption peak of NIR-II LNPs at 1055 nm increased nearly 7.8-fold due to protonation of nitrogen atoms and electronic rearrangement forming a large π-conjugated system in Cy-lipid. When NIR-II LNPs are endocytosed into cells, photothermal transduction mediated by 1064 nm laser irradiation of Cy-lipid induces morphological changes in LNPs, thereby accelerating mRNA escape from endosomes. This results in a threefold increase in translation efficiency of eGFP-encoding mRNA at the cellular level and a 4.5-fold increase in translation efficiency of luciferase-encoding mRNA in the liver.

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