By Fineline Cube 
Sirius Therapeutics announced that the first patient has been dosed in a Phase II clinical trial of SRSD216, a novel small interfering RNA (siRNA) therapy targeting elevated lipoprotein(a) levels (hyperlipoproteinemia). The drug demonstrated up to 95% reduction in lipoprotein(a) in Phase I interim data with effects lasting at least 12 weeks after a single subcutaneous dose.
Clinical Milestone
| Item | Detail |
|---|---|
| Product | SRSD216 (siRNA therapy) |
| Company | Sirius Therapeutics |
| Mechanism | LPA gene silencing, reducing apolipoprotein(a) production |
| Indication | Hyperlipoproteinemia (elevated lipoprotein(a)) |
| Trial | Phase II, first patient dosed (31 Dec 2025) |
| Phase I Interim Data | Up to 95% lipoprotein(a) reduction at 3 months, duration ≥12 weeks |
| Safety | Favorable profile, no clinically significant risks observed |
Mechanism of Action & Differentiation
- Target: LPA gene encoding apolipoprotein(a), the key component of lipoprotein(a) particles
- Delivery: Subcutaneous injection with proprietary GalNAc conjugation for liver‑specific uptake
- Duration: Single dose maintains efficacy for ≥12 weeks, supporting quarterly or less frequent dosing
- Selectivity: High target specificity with minimal off‑target effects in preclinical models
- Competitive Edge: Potentially longer‑lasting than antisense alternatives; first‑in‑class siRNA in China for Lp(a) reduction
Clinical Development Pathway
Phase I Study:
- Ongoing follow‑up of dosed participants
- Primary completion expected Q2 2026
- Data supports advancement to Phase II without dose‑limiting toxicities
Phase II Trial Design:
- Population: ~120 patients with baseline lipoprotein(a) ≥125 nmol/L and elevated cardiovascular risk
- Primary Endpoint: Percent change in lipoprotein(a) from baseline to Week 24
- Secondary Endpoints: Time‑averaged reduction, safety, LDL‑C changes, inflammatory markers
- Sites: 15 centers across China, with potential US/EU expansion pending Phase II data
Market Opportunity
Hyperlipoproteinemia(a) Burden:
- Global prevalence: ~20‑30% of population have elevated lipoprotein(a) (>125 nmol/L)
- China patients: >200 million individuals with elevated Lp(a), independent cardiovascular risk factor
- Unmet Need: No approved therapies specifically for Lp(a) reduction in China; statins and PCSK9 inhibitors have minimal effect
| Parameter | 2027E | 2029E | 2031E |
|---|---|---|---|
| Addressable patients (China) | 50 million | 60 million | 70 million |
| Peak penetration | 2% | 5% | 8% |
| Annual therapy cost (¥) | ¥45,000 | ¥38,000 (post‑NRDL) | ¥32,000 |
| China market potential | ¥45 billion | ¥114 billion | ¥179 billion (US$6‑25 billion) |
Competitive Landscape
| Drug | Company | Mechanism | Stage | Key Differentiator |
|---|---|---|---|---|
| SRSD216 | Sirius Therapeutics | siRNA (LPA) | Phase II | 95% reduction, ≥12‑week duration |
| Pelacarsen | Novartis/Ionis | Antisense oligonucleotide | Phase III (Lp(a)HORIZON) | Monthly injections, ~80‑90% reduction |
| Olpasiran | Amgen | siRNA (LPA) | Phase III (OCEAN(a)-DOSE) | Quarterly dosing, ~90% reduction |
| Lepodisiran | Eli Lilly | siRNA (LPA) | Phase II | Longer‑acting, early data |
Strategic Position: SRSD216’s Phase I durability data (≥12 weeks) suggests potential for quarterly or bi‑annual dosing, offering competitive advantage over monthly antisense therapies.
Company Background & Financial Position
- Founded: 2021 by world‑class management team and top‑tier investors
- Operations: Innovation R&D center in United States, translational medicine center in China
- Funding: Nearly USD 150 million raised cumulatively
- Investor Syndicate: OrbiMed, Creacion Ventures, Hankang Capital, Delos Capital, BioTrack Capital
- Runway: Funding supports operations through Phase II completion and Phase III initiation (2027)
Development Timeline & Financial Outlook
| Milestone | Target Date | Investment (USD) |
|---|---|---|
| Phase II interim data | Q4 2026 | $25 million |
| Phase II completion | Q2 2027 | $40 million |
| Phase III initiation | H2 2027 | $120 million |
| NDA filing | 2029 | $80 million |
| Potential approval | 2030 | – |
| Peak sales potential (global) | 2032+ | $3‑5 billion |
Forward‑Looking Statements
This brief contains forward‑looking statements regarding SRSD216’s clinical development, market potential, and competitive positioning. Actual results may differ materially due to clinical trial outcomes, regulatory decisions, and competitive dynamics.-Fineline Info & Tech