On June 10, RayzeBio, a wholly owned subsidiary of Bristol Myers Squibb (BMS), signed a definitive agreement with Philochem AG, a wholly owned subsidiary of Philogen Group. Under this agreement, Philochem will grant RayzeBio global rights to develop, manufacture, and commercialize OncoACP3—a clinical-stage therapeutic and diagnostic agent for cancer. Following the moves by giants like Novartis, Eli Lilly, and AstraZeneca, the radiopharmaceutical field continues to heat up. Could radiopharmaceuticals become the next “PD-1-level” golden track?
FAP (fibroblast activation protein) and ACP3 (acid phosphatase, prostate-specific) have emerged as two major targets in this field, representing distinct strategic directions—tumor microenvironment modulation for pan-cancer indications and precision diagnosis and treatment for prostate cancer, respectively. Below is a comparative analysis based on biological properties, R&D progress, technical advances, and market potential.
I. Biological Characteristics and Mechanisms
FAP: The “Universal Key” to the Tumor Microenvironment
Expression profile: Highly expressed in cancer-associated fibroblasts (CAFs) of over 90% of epithelial-origin tumors, such as pancreatic, breast, and colorectal cancers, with negligible expression in normal tissues—showing strong tumor specificity.
Functional mechanism: Promotes extracellular matrix remodeling, tumor invasion, and metastasis through protease activity while suppressing antitumor immune responses.
Advantages: Targeting CAFs allows for indirect killing of multiple solid tumors, offering broad therapeutic potential. Clinically, FAP can be used for both diagnosis (e.g., ⁶⁸Ga-FAPI-PET/CT) and therapy (e.g., ¹⁷⁷Lu/²²⁵Ac-labeled drugs).
ACP3: The “Exclusive Target” for Prostate Cancer
Expression profile: Highly expressed only in prostate cancer tissues, with minimal expression in other organs (except the healthy prostate), showing organ-level specificity.
Functional mechanism: As a novel prostate cancer target, it participates in tumor growth signaling pathways, and its high specificity substantially reduces the risk of off-target toxicity.
Advantages: Offers “absolute precision” in prostate cancer diagnosis and therapy, particularly suited for tackling metastatic castration-resistant prostate cancer (mCRPC).
Core Biological Differences Between FAP and ACP3:
II. R&D Pipelines and Technological Breakthroughs
FAP Target: Big Pharma Betting Heavily, Accelerating Innovation
Global Landscape:
- Novartis: Broadest portfolio, including FAPI-46 (Phase II, diagnostic), FAPI-74 (Phase II, diagnostic), and ¹⁷⁷Lu-FAP-2286 (Phase II, therapeutic).
- Eli Lilly: Gained ¹⁷⁷Lu-PNT6555 (Phase I, therapeutic) and ²²⁵Ac-PNT6555 (preclinical) through its acquisition of POINT Biopharma.
- Chinese companies: Dongcheng Pharmaceutical (LanNuoCheng)’s ¹⁷⁷Lu-LNC1004 has received clinical approvals in China and the US; Farber New Sky is advancing ⁹⁹ᵐTc-H7ND as a diagnostic agent.
ACP3 Target: BMS’s Billion-Dollar Bet Sets Benchmark for Theranostics
Core Asset – OncoACP3:
- Design: Diagnostic version (⁶⁸Ga-labeled) enables PET imaging; therapeutic version (²²⁵Ac-labeled) emits alpha particles to precisely destroy tumors.
- Clinical advantages: Tumor retention >48 hours; healthy tissue accumulation <0.1%, indicating extremely low off-target toxicity.
- Deal details: RayzeBio (BMS subsidiary) acquired global rights for $1.35 billion (including $350 million upfront and $1 billion in milestones).
Competitive Landscape: Six global companies are developing ACP3 programs, including Bayer and Johnson & Johnson. In China, Hengrui Medicine is advancing HRS-4357 (therapeutic) and HRS-9815 (diagnostic) pipelines.
III. Market Potential and Indication Expansion
FAP: The Key to a Trillion-Yuan Pan-Cancer Market
Diagnostic demand: Multiple FAPI-PET imaging agents are now in Phase II clinical trials globally. The Chinese imaging diagnostics market is projected to reach RMB 26 billion by 2030.
Therapeutic opportunity: Covers high-mortality cancers like pancreatic and breast cancer with large patient populations. If Novartis’s FAP-2286 is approved, annual sales could exceed $1 billion.
ACP3: A Blue Ocean in Precision Prostate Cancer Therapy
Patient population: 1.34 million new prostate cancer cases annually worldwide; 40% progress to resistant mCRPC, with only a 30% five-year survival rate.
Benchmark drug: Novartis’s Pluvicto (PSMA-targeted) reached $2.5 billion in sales in 2024 but is limited by nephrotoxicity. ACP3’s minimal expression in normal tissues offers a clear safety edge.
Market outlook: If approved, OncoACP3 could capture part of Pluvicto’s market and become the next blockbuster in radiopharmaceuticals.
IV. Two Targets, One Golden Track
FAP is more suited for multi-cancer platform expansion, with fast technology iteration (e.g., CTR) and strong industry investment, potentially becoming the next “PD-1-level” therapy.
ACP3, focused on the massive prostate cancer market, leverages ultra-high specificity and BMS’s heavy investment to achieve faster clinical translation.
The radiopharmaceutical race ultimately hinges on the dual dynamics of target scarcity and radionuclide precision. FAP wins in breadth of indications, ACP3 excels in targeting accuracy—together, they are propelling oncology toward a new era of “see it, destroy it” precision treatment.
To accelerate FAP-targeted drug development, Kyinno Biotechnology has leveraged its robust engineered cell development platform to establish a series of FAP-overexpressing cell lines and tumor-bearing mouse models. Partial validation data are shown below. Meanwhile, ACP3 cell lines and in vivo models will soon be available. Contact us for more information.
FAP-Related Cell Lines:
- KC-1422 293T-FAP
- KC-2635 HT1080-FAP
- KC-2798 CT26-FAP
- KC-2825 MC38-FAP
- KC-1284 CT26-mouse-Fap
- KC-2181 NIH/3T3-mouse-Fap
- KC-2953 PC3-FAP-High
- KC-5455 NIH/3T3-FAP
In Vivo Model Validation
KC-1422 293T-FAP
KC-2635 HT1080-FAP
