Novartis Launches Ultra-Long-Acting Lipid-Lowering siRNA Drug Inclisiran in China at ¥9,988 per Dose, Administered Twice Yearly

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Recently, the first prescriptions for Inclisran injection (Inclisran), an ultra-long-acting lipid-lowering drug developed by Novartis that is administered twice a year, have been issued in Beijing, with each dose priced at 9,988 yuan.

Among them, Inclisran, developed by Alnylam, is the world's first siRNA PCSK9 inhibitor. Its ultra-long duration of action gives it an advantage over PCSK9 monoclonal antibodies. The drug was approved in China this August, and also in the same month, IBI (Innovent Biologics)’s PCSK9 monoclonal antibody, Torliprilamab, was approved for marketing. Now that Novartis has set an unexpectedly high price, a price war targeting the PCSK9 pathway may be triggered.

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Omega Therapeutics, focused on developing novel programmable epigenomic mRNA medicines, announced new clinical data regarding OTX-2101. OTX-2101 is a c-MYC-targeted epigenomic controller (MYC-EC) being developed for use with immune checkpoint inhibitors.

Omega Therapeutics is a clinical-stage biotechnology company pioneering the development of a new class of programmable epigenomic mRNA medicines to treat or cure a wide range of diseases. By regulating gene expression at the pre-transcriptional level, Omega’s approach enables controlled epigenomic modulation of nearly any human gene without altering the native nucleic acid sequence, including historically undruggable and difficult-to-treat targets.

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TransCode Therapeutics, dedicated to using RNA therapies for cancer treatment, announced that its immunotherapy candidate TTX-RIGA successfully treated preclinical melanoma, showing significant inhibition of tumor growth in the study.

TTX-RIGA is an innovative immunotherapy candidate built around TransCode's proprietary TTX delivery platform. It aims to activate the immune system against tumor cells, potentially offering effective treatment for various primary, metastatic, and recurrent cancers. TTX-RIGA is designed to function by binding to an intracellular receptor called RIG-I (retinoic acid-inducible gene I). In a mouse model of melanoma, systemic administration of TTX-RIGA demonstrated that the therapeutic candidate effectively reduced the growth of primary tumors. Notably, it also triggered an immune response against secondary recurrent tumors, inhibiting their growth by 70%.

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On 2023-10-19, BioNTech announced the initiation of a Phase II clinical trial (NCT05968326) for BNT122 (Autogene cevumeran), an mRNA-based personalized neoantigen-specific immunotherapy (iNeST), as adjuvant treatment for resected pancreatic ductal adenocarcinoma (PDAC). The first patient dosing in the Phase II trial has recently been completed.

The launch of this Phase II trial for PDAC patients is based on the positive results from the earlier Phase I trial (NCT04161755). The full results of the Phase I trial were published in Nature on May 11, 2023. The Phase I results showed that the combination regimen of Autogene cevumeran with the anti-PD-L1 immune checkpoint inhibitor atezolizumab and mFOLFIRINOX chemotherapy significantly delayed recurrence time in resected PDAC patients, induced a large number of neoantigen-specific, functional, and durable CD8+ active T cells, and demonstrated good safety. The Phase II trial is expected to recruit approximately 260 PDAC patients in the United States, Europe, and the Asia-Pacific region.

Among them, BNT122 (Autogene cevumeran), a therapeutic personalized tumor vaccine jointly developed by BioNTech and Genentech, encodes up to 20 patient-specific MHC class I and II restricted neoantigens. This collaboration began in 2016 and is currently being evaluated in various solid tumor indications, including the ongoing Phase 2 trial for adjuvant treatment of surgically resected colorectal cancer, the Phase 2 trial in combination with pembrolizumab for advanced melanoma, and the Phase Ia/b trial for advanced or metastatic tumors.

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Regulus Therapeutics, focused on the development of miRNA, announced that after reviewing all available safety data, the third cohort of patients will be enrolled in the Phase 1b MAD study of RGSL8429 for the treatment of ADPKD.

Phase Ⅰb MAD Study is a double-blind, placebo-controlled trial evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics (PK/PD) of RGLS8429 in adult patients with ADPKD. The study will assess three different dose levels of RGLS8429 treatment, including measurements of polycystin changes, height-adjusted total kidney volume (htTKV), cyst structure, and overall renal function. The first cohort receiving 1 mg/kg of RGLS8429 or placebo every other week for three months is expected to report primary data within the coming weeks. The second group of patients will receive 2 mg/kg of RGLS8429 or placebo every other week for three months. The company anticipates initiating dosing for the third cohort in October 2023 after reviewing all available safety data from Group 2.

Among them, RGLS8429 is a novel next-generation oligonucleotide drug for the treatment of ADPKD, designed to inhibit miR-17 and preferentially target the kidneys. Administration of RGLS8429 has shown robust data in preclinical models, with significant improvements in indicators of renal function, size, and other measures of disease severity compared to Regulus' first-generation compound RGLS4326, along with superior pharmacological characteristics in preclinical studies.

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On October 19, 2023, the CDE official website announced that the phase 1 new drug TQA3038 injection, submitted by Zhengda Tianqing, received tacit approval for clinical trials. It is intended to be developed for the treatment of chronic hepatitis B. According to publicly available information from Zhengda Tianqing, TQA3038 is a small interfering RNA (siRNA) drug independently developed by the company that targets the hepatitis B virus (HBV).

Among them, TQA3038 is an N-acetylgalactosamine (GalNAc)-conjugated siRNA drug that can accumulate in the liver. The product effectively degrades targeted RNA and inhibits the translation of related proteins by forming an RNA-induced silencing complex with proteins such as Ago2 in cells, thereby blocking the replication of the hepatitis B virus. It is expected to significantly improve the "functional cure" rate in patients in clinical practice.

According to an earlier press release by Chia Tai Tianqing, TQA3038 utilizes an innovative nucleic acid sequence and demonstrates stronger antiviral activity both in vitro and in vivo compared to similar products. Non-clinical study results show that TQA3038 can significantly inhibit infection markers in AAV-HBV model mice; it has exhibited good safety and tolerability in rat and cynomolgus monkey toxicology tests, with a wide safety margin. The approval of TQA3038 injection for clinical trials in the field of hepatitis B will further expand Chia Tai Tianqing's pipeline of innovative drugs in the liver disease sector.

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On October 19, 2023, Flagship Pioneering, a renowned venture capital firm in the biotechnology sector, announced the merger of its incubated circular RNA company Laronde with Senda Biosciences, which designs programmable nanoparticles using artificial intelligence, to launch a new company, Sail Biomedicines. The financial details of the merger were not disclosed. The total funding for the newly merged company is expected to exceed $800 million, including the $490 million raised by Laronde in 2021 and the $309 million raised by Senda Biosciences. Guillaume Pfefer, CEO Partner at Flagship and CEO of Senda, will serve as the CEO of the new company. John Mendlein, interim CEO and Chairman of the Board of Laronde and Executive Partner at Flagship, will serve as the Executive Chairman of the new company.

The announcement shows that the new company will use generative artificial intelligence technology to identify and design drugs that are targeted, multifunctional, and fully programmable with adjustability. Senda has launched the first nanoparticle platform based on universal chemical codes, which can directly deploy payloads (such as translatable RNA) to selected cells and tissues. Laronde’s pioneering Endless RNA (eRNA) technology aims to design and develop circular RNA-related therapies, which can be programmed to express various proteins in the body, holding immense therapeutic potential.

Currently, Senda and Laronde's newly merged company, Sail Biomedicines, has not publicly disclosed its research pipeline.