On September 2, Novartis reached a BD deal with Arrowhead for siRNA therapy ARO-SNCA, featuring a $200 million upfront payment and potential milestone payments up to $2 billion. The following day, Novartis struck another BD deal with Voyager Therapeutics for four siRNA drugs worth over $5.2 billion. These two consecutive deals totaling over $7 billion sent strong signals to the market and focused investor attention on the increasingly prominent small nucleic acid sector.

In fact, as early as May this year, global gene editing giant CRISPR Therapeutics invested $895 million (approximately RMB 6.5 billion) in a major collaboration with domestic innovative drug company Sirius Therapeutics to jointly advance the development of innovative siRNA therapies. This marked the third BD overseas deal in China's small nucleic acid sector. It is precisely this BD track record that has made Sirius Therapeutics' Hong Kong IPO highly anticipated.

According to sources, on September 28, Sirius Therapeutics officially submitted its prospectus to the Hong Kong Stock Exchange, with Goldman Sachs, Haitong International, and HSBC serving as joint sponsors.

**siRNA Therapy Track Becomes the Next "Hot Commodity"**

According to a Frost & Sullivan report, the global siRNA therapy market reached $2.4 billion in 2024 and is expected to grow to $50.3 billion by 2040, representing a compound annual growth rate of 20.9%. Currently, 22 products have been approved for market (including withdrawn products), including 7 siRNA drugs, 13 ASO drugs, and 2 aptamers. Meanwhile, over 1,200 small nucleic acid new drugs are under global development.

Since the beginning of this year, the small nucleic acid track has gained widespread investor attention, supported by innovative technological breakthroughs and sales performance. Besides Novartis's aggressive entry with over $7 billion mentioned above, US small nucleic acid concept stocks Alnylam, Ionis, and Avidity have all seen varying degrees of stock price increases since early this year. Alnylam, leveraging the better-than-expected sales performance of its RNAi therapy Amvuttra, achieved a maximum stock price increase of 105.78% this year, with market capitalization exceeding $60 billion.

Compared to overseas markets, domestic small nucleic acid drugs started relatively late, with only 3 imported new drugs currently on the market: nusinersen and tofersen developed by Biogen and Ionis, and inclisiran developed by Novartis and Alnylam. However, domestic small nucleic acid new drug R&D pipelines are rapidly expanding, ranking second only to the United States in quantity. Currently, over 300 new drugs are under development, with nearly 70 entering clinical stages.

Financing activities in the small nucleic acid drug sector have been equally frequent this year, with multiple companies receiving new funding support. For example, in April, Scenery Biotechnology received Pre-A round financing; in May, HaoBo Medical obtained $50 million through B+ round financing; in the same month, Sirius Therapeutics received nearly $50 million in B2 round financing; in August, Haichangbio obtained nearly RMB 500 million through C round financing; also in August, RiboBio raised over RMB 200 million through private equity financing.

According to incomplete statistics, 8 domestic small nucleic acid companies have received financing this year, with HaoBo Medical, Sirius Therapeutics, and RiboBio all completing over RMB 200 million in financing.

Since its establishment, Sirius Therapeutics, which filed for Hong Kong IPO, has completed three rounds of financing. After completing $47.5 million in B2 round financing in May this year, its post-investment valuation reached $253 million.

**Behind the Nearly $900 Million Heavyweight BD Deal**

The nearly $900 million BD deal between Sirius Therapeutics and CRISPR Therapeutics in May deserves investor attention not only because it was the third BD overseas deal in China's small nucleic acid sector, but also because it represents one of the few "high transaction amount, joint development and joint commercialization" models.

According to the company's prospectus, Sirius Therapeutics' FXI siRNA adopts a 50:50 joint development model with CRISPR Therapeutics, whereby Sirius Therapeutics received $25 million in cash and $70 million in equity from CRISPR Therapeutics, plus $800 million in milestone payments.

This all stems from Sirius Therapeutics' core pipeline varieties with FIC/BIC potential. Since its establishment, Sirius Therapeutics has been committed to fully leveraging the clinical and commercial value of siRNA therapies. The company has established a rich and competitively advantaged product pipeline, including one core variety - FXI siRNA (SRSD107) for treating coagulation disorders, and two heavyweight varieties Lp(a) siRNA (SRSD216) and INHBE siRNA (SRSD384) for treating cardiometabolic diseases and obesity, respectively.

The most noteworthy and the subject of collaboration with CRISPR Therapeutics is Sirius Therapeutics' core variety SRSD107. As the company's core product, SRSD107 is a potentially first-in-class siRNA drug targeting coagulation factor XI. From a mechanism perspective, as a double-stranded small interfering RNA (siRNA) drug with proprietary intellectual property owned by Sirius Therapeutics, SRSD107 targets coagulation factor XI (FXI) and is expected to reduce thrombotic events while significantly reducing bleeding risk.

Its potent and durable effects and good safety profile position SRSD107 as a potentially FIC/BIC next-generation safer anticoagulant drug. Its potential indications are broad, covering atrial fibrillation, venous thromboembolism (VTE), tumor-associated thrombosis, end-stage renal disease patients receiving hemodialysis, and major orthopedic surgery populations where bleeding risk limits existing treatment options.

Previous clinical results showed that FXI siRNA administration can achieve sustained FXI inhibition for up to 6 months, demonstrating impressive FIC/BIC potential, which became a key factor in attracting MNC attention. The product is currently conducting Phase II multicenter clinical trials in Europe and plans to initiate another Phase II trial in China and Australia/New Zealand.

Notably, the standard treatment for antithrombotic therapy has long been based on "-ban" drugs, with veteran anticoagulant apixaban achieving over $20 billion in sales in 2024, but potential bleeding risk has always been a pain point of this therapy. Supported by good clinical data, SRSD107 as an siRNA therapy is expected to capture broad commercial market space.

Besides its core variety, another heavyweight product in Sirius Therapeutics' pipeline, Lp(a) siRNA, is also in Phase II clinical stage. Phase I clinical data showed that 300mg and 600mg dose groups achieved over 95% inhibition 43 days after administration, with sustained inhibition lasting at least 12 weeks, with follow-up still ongoing, potentially achieving twice-yearly or even annual injections.

Supported by clinical data and high patient compliance, its commercialization prospects are equally promising.

Financially, although the company posted net losses of RMB 309 million and RMB 342 million in 2023 and 2024 respectively, supported by cash flow from BD deals, the company achieved profitability in the first half of this year with net profit of RMB 34.461 million. Current cash and cash equivalents increased to RMB 618 million, sufficient to meet the company's R&D investment needs for nearly 3 years. The company also expects to receive $800 million in milestone payments from CRISPR Therapeutics, providing stable cash flow with high growth certainty. Therefore, against the backdrop of the continuing bull market for innovative drugs in Hong Kong stocks, this company deserves investor attention.