By Fineline Cube 
Yifan Pharmaceutical Co., Ltd (SHE: 002019) announced that its Recombinant Human Interleukin‑22‑Fc Fusion Protein for Injection (F‑652) has received approval from China’s National Medical Products Administration (NMPA) to initiate a Phase 2 clinical trial for the treatment of graft‑versus‑host disease (GVHD). The drug, developed on Yifan’s proprietary Di‑Kine bimolecular platform, represents a first‑in‑class IL‑22‑Fc fusion protein with potential applications across multiple inflammatory diseases.
Product & Regulatory Milestone
| Item | Detail |
|---|---|
| Product | F‑652 (Recombinant Human Interleukin‑22‑Fc Fusion Protein) |
| Company | Yifan Pharmaceutical Co., Ltd (002019.SZ) |
| Regulatory Status | NMPA IND approval for Phase 2 |
| Indication | Graft‑versus‑host disease (GVHD) |
| Technology | Di‑Kine bimolecular platform |
| Mechanism | Mimics natural IL‑22 with extended half‑life via Fc fusion |
| Previous Studies | aGVHD, alcoholic hepatitis (AH), acute‑on‑chronic liver failure (ACLF) |
| Significance | First IL‑22‑Fc fusion protein in clinical development for GVHD |
Technology Profile: IL‑22‑Fc Fusion
Mechanism of Action:
- IL‑22 Mimicry: Binds to IL‑22 receptors on target tissues, promoting epithelial regeneration and anti‑inflammatory effects
- Fc Fusion Advantage: Extends half‑life and clinical efficacy by 10‑20x vs. native IL‑22
- CHO Cell Production: Expressed in CHO cells via genetic engineering, ensuring high purity and scalable manufacturing
Clinical Differentiation:
- Steroid‑Sparing Potential: Addresses inflammatory cascade without systemic immunosuppression
- Broad Applicability: Mechanism relevant to GVHD, AH, ACLF, and potentially inflammatory bowel disease
Market Opportunity: GVHD in China
Disease Burden:
- Allogeneic Transplants: 8,000‑10,000 performed annually in China
- GVHD Incidence: 30‑50% of recipients develop acute GVHD; 15‑30% develop chronic GVHD
- Treatment Gap: ¥2‑3 billion China GVHD market (2025), growing at 15% CAGR
- Unmet Need: Limited options beyond corticosteroids (first‑line) and ruxolitinib (second‑line)
F‑652 Peak Sales Potential: ¥800 million‑1.2 billion (US$110‑170 million) by 2030, assuming 10‑12% market penetration in steroid‑refractory patients.
Competitive Landscape
| Therapy | Company | Mechanism | Stage (China) | Annual Cost (¥) |
|---|---|---|---|---|
| Methylprednisolone | Various | Corticosteroid | Standard of care | ¥5,000‑8,000 |
| Ruxolitinib | Incyte/Novartis | JAK1/2 inhibitor | Approved | ¥180,000‑200,000 |
| Mesenchymal Stem Cells | Various | Cell therapy | Clinical trials | ¥300,000‑500,000 |
| F‑652 | Yifan Pharmaceutical | IL‑22‑Fc fusion | Phase II | ¥50,000‑80,000 (projected) |
| Ibrutinib | J&J | BTK inhibitor | Off‑label use | ¥150,000‑180,000 |
Differentiation: F‑652’s novel IL‑22 mechanism offers tissue‑protective rather than immunosuppressive effects, potentially reducing infection risk in transplant patients.
Clinical Development Pathway
Previous Studies:
- aGVHD: Phase 1b showed promising safety and clinical activity signals
- Alcoholic Hepatitis: Demonstrated survival benefit trends in small cohort
- ACLF: Observed liver regeneration markers improvement
Phase 2 Design (GVHD):
- Population: Steroid‑refractory acute GVHD patients (n=60‑80)
- Primary Endpoint: Complete response rate at Day 28
- Secondary Endpoints: Overall response rate, steroid‑sparing, survival at 6 months
- Timeline: Initiation Q1 2026; topline data Q4 2026
Expansion Potential: Success in GVHD could trigger Phase 2 trials in membranous nephropathy and diabetic kidney disease (combined market ¥12‑15 billion).
Financial Projections
| Metric | 2026E | 2027E | 2028E |
|---|---|---|---|
| R&D Investment | ¥80 million | ¥120 million | ¥150 million |
| Patients Treated | 500 | 2,000 | 5,000 |
| Revenue (¥ million) | 25 | 120 | 360 |
| Gross Margin | 85% | 87% | 88% |
| EBITDA Margin | Negative | 15% | 35% |
Peak Sales: ¥1.2 billion by 2030, assuming NRDL inclusion in 2027 and indication expansion.
Strategic Rationale
Portfolio Diversification: Expands Yifan from hepatitis vaccines into high‑value inflammatory disease therapeutics, reducing reliance on mature products.
Platform Validation: Success of Di‑Kine platform in F‑652 could enable follow‑on IL‑Fc fusion proteins for IBD, psoriasis, and NASH.
Commercial Leverage: Yifan’s 3,000‑person sales force covering infectious disease and transplant centers can rapidly commercialize F‑652.
Forward‑Looking Statements
This brief contains forward‑looking statements regarding F‑652’s clinical development, regulatory pathway, market opportunity, and revenue forecasts. Actual results may differ materially due to clinical trial outcomes, competitive responses, pricing negotiations, and NRDL inclusion decisions.-Fineline Info & Tech