Sirius Therapeutics-B in HK IPO Race: siRNA Therapy as Its Ace Card, But Commercialization Remains a Distant Star

The Rapid Rise and Hidden Concerns of siRNA Newcomers.

Source｜Medical Research Society

Hong Kong IPO Continues to Dance.

According to the statistics from PharmaCube, from September 22 to September 29, one pharmaceutical company has passed the hearing in the Hong Kong stock market, and four innovative pharmaceutical and device companies have submitted listing applications. Among them, a young pharmaceutical company established in 2021 that is dedicated to the development of siRNA (small interfering RNA) therapies has attracted considerable attention.

This company is Sirius Therapeutics, which has currently submitted its listing application to the Hong Kong Stock Exchange, with Goldman Sachs, Haitong International, and HSBC serving as joint sponsors. It is reported that within approximately four years of its establishment, the company has "aggressively raised funds": completing a US$60 million Series B financing round in October 2023, and a US$50 million Series B+ financing round in May 2025, with cumulative financing nearing US$150 million. Investors include Boyuan Capital, OrbiMed, Hongyuan Capital, H&Q Healthcare Fund, and others.

In addition, in May this year, Sirius Therapeutics reached a strategic partnership with CRISPR Therapeutics (hereinafter referred to as "CRISPR"). Both parties plan to share costs and profits globally at a 50:50 ratio to advance the development and commercialization of Sirius Therapeutics' next-generation long-acting siRNA therapy, SRSD107. This includes research funding support provided under a joint research plan.

According to the cooperation agreement, Sirius Therapeutics can receive $95 million in cash and cash equivalents as an upfront payment from CRISPR Therapeutics and is eligible to receive over $800 million in advance and milestone payments, with a potential total payment exceeding $895 million (approximately 6.4585 billion yuan).

At present, Sirius Therapeutics has become a "hot commodity" in the capital market. How did they achieve this? Being "popular" in the primary market guarantees a successful IPO, right?

Behind the Nearly $900 Million BD Deal

For the industry, the nearly $900 million BD deal achieved by Sirius Therapeutics in May is highly significant: it marks the third BD overseas collaboration in China's small nucleic acid sector and represents a rare model of "high transaction value, co-development, and co-commercialization."

Moreover, CRISPR Therapeutics is no ordinary company. Co-founded by a Nobel Prize winner in Chemistry, it went public on NASDAQ in 2016. As a biopharmaceutical company dedicated to developing transformative nucleic acid medicines for treating severe diseases, it currently holds a diversified portfolio of product candidates spanning a wide range of disease areas, including hemoglobinopathies, oncology, regenerative medicine, cardiovascular diseases, autoimmune diseases, and rare diseases.

In 2018, CRISPR advanced the first CRISPR/Cas9 gene-editing therapy into clinical trials for the study of sickle cell disease and transfusion-dependent beta-thalassemia, successfully developing the approved product CASGEVY®.

Overall, CRISPR Therapeutics is a leading gene therapy developer with extensive experience and a global market focus. Through long-term and in-depth collaboration, it should be able to provide significant support to Sirius Therapeutics. But how did this company come to notice Sirius Therapeutics, a startup in the pharmaceutical industry?

In fact, Sirius Therapeutics started from a high point. According to public information, the company was founded by globally renowned...HealthcareOrbiMed Entities, a health investment institution, and Creacion Ventures jointly established, have set up a dual-headquarters structure in the United States and China, with the United States headquarters in San Diego focusing on source innovation and the China headquarters in Shanghai concentrating on translational medicine and clinical development, targeting the global market.

Dr. Qunsheng Ji, Executive Director and Chief Executive Officer, has over 25 years of experience in drug research and development, translational medicine, and business management. He previously served as Director and Head of Bioscience at AstraZeneca, and as Vice President and Head of Oncology and Immunology at WuXi AppTec.

However, such a founding background is not the decisive factor for attracting capital and partners. For an innovative pharmaceutical company, what matters more are technology, products, and the market.

The "Money-Making" Code of Sirius Therapeutics

Many industry insiders believe that Sirius Therapeutics is a dark horse in the siRNA field, which makes sense.

First, at the technical level. The prospectus shows that, compared with traditional small molecule or antibody drugs, siRNA therapy has fundamental advantages of "upstream intervention, long-term suppression, and broad targets." It can selectively silence various disease-related genes, thereby significantly reducing the expression of related proteins in a variety of diseases (such as genetic disorders, viral infections, tumors, and metabolic diseases).

To fully leverage the advantages of siRNA therapy, Sirius Therapeutics has independently developed the PEPR platform, which features chemical modification, target and sequence selection, siRNA sequence design and optimization, as well as advanced delivery technology.

Among them, chemical modifications can minimize off-target effects and enhance safety, thereby broadening the potential therapeutic window, which is crucial for treating chronic diseases; extrahepatic delivery systems can expand the scope of siRNA from the liver to tissues such as fat, skeletal muscle, heart, kidneys, and the central nervous system.

The advantages of the aforementioned technology platforms also form the basis for Sirius Therapeutics to enrich its product pipeline and develop first-in-class and best-in-class drugs.

Specifically, at the product level, according to the prospectus, the main product assets of Sirius Therapeutics include SRSD107, SRSD216, SRSD384, etc.

Among them, SRSD107, the core product, aims to selectively inhibit coagulation factor XI (FXI). It is the top priority of the collaboration between Sirius Therapeutics and CRISPR Therapeutics. Currently, it is undergoing a Phase II multicenter clinical trial for venous thromboembolism (VTE) in Europe, with plans to initiate Phase II trials for cardiovascular diseases in China, Australia, and New Zealand. SRSD216 is a potential best-in-class siRNA targeting Lp(a) for cardiometabolic diseases, currently in Phase IIa trials in China and the United States. SRSD384 is a candidate drug targeting INHBE for obesity, advancing towards the new drug clinical trial application stage.

This also offers a glimpse into the market prospects of Sirius Therapeutics.

The prospectus mentions that in 2024, the treatment fields of coagulation disorders, cardiometabolic diseases, and obesity each have at least one of the three blockbuster drugs with global annual sales exceeding 10 billion US dollars, along with various other drugs with annual sales reaching several billion US dollars. Once siRNA technology matures, the market size of related products may far exceed the existing therapeutic paradigms.

In response, some research institutions have made positive predictions. According to a Frost & Sullivan report, the global siRNA therapy market size will reach 2.4 billion US dollars in 2024 and is expected to grow to 50.3 billion US dollars by 2040, with a compound annual growth rate of 20.9%.

The眼光 of capital is often sharp. Many investors favor Sirius Therapeutics, perhaps seeing the company's long-term value in technology, products, and the market. However, a pharmaceutical company with a relatively short establishment period, no matter how high its starting point or how accurate its positioning, cannot avoid the challenges of growth.

Start-up pharmaceutical companies face growth challenges

Currently, the operating difficulties of Sirius Therapeutics are still quite prominent.

The prospectus shows that, due to not having entered the commercialization stage, Sirius Therapeutics' total revenue remained at 0 from 2023 to the first half of 2025. The net profits for the periods were -309 million yuan, -342 million yuan, and 34.461 million yuan, respectively. The profit achieved in the first half of this year was mainly due to the fair value change of CRISPR Therapeutics shares received when the company obtained the upfront payment from its collaboration with CRISPR.

It is worth mentioning that R&D expenses decreased by 31.3% year-on-year to 64.667 million yuan in the first half of the year. Sirius Therapeutics explained that this was related to the company’s pipeline development schedule, under which the company incurred significant expenses in 2024 for the Phase I trial of SRSD107 and the preclinical research of SRSD216.

Some investors believe that this phased decrease might be to optimize financial statements for the IPO. As pipeline clinical research continues to advance, R&D expenditures will only increase, highlighting the urgency of the IPO and establishing strategic partnerships. "For startups like us, independently developing such products is not realistic. We need to find partners who share our vision to move forward together," said Dr. Ji Qunsheng.

However, a more realistic issue is that market competition continues to intensify.

It is important to note that siRNA is not a particularly niche field. The prospectus mentions that since the approval of the first siRNA drug, Onpattro® (patisiran), in 2018, siRNA therapy has achieved significant clinical and commercial validation. As of the latest practicable date, seven siRNA products have been approved for marketing in major global markets, with major players such as Novartis, Sanofi, and Alnylam heavily involved.

In the FXI inhibitor-targeted siRNA therapy track where the core product SRSD107 is located, Sirius Therapeutics is also in a race with companies like Ribo, Sirnaomics, and ADARx.

From this perspective, it remains uncertain whether Sirius Therapeutics can maintain long-term advantages in technology, products, and other aspects, how significant the benefits of cooperation with partners like CRISPR Therapeutics will be, and when its core products will achieve commercial breakthroughs.

*The material of this article is mainly from the public prospectus, for reference only, and does not constitute any investment advice.

       Title: Sirius Therapeutics in the Battle of Hong Kong IPOs: siRNA Therapy as the Secret Weapon, but Commercialization Still a Distant Star