XtalPi(2228.HK) Derives IgA Nephropathy siRNA Preclinical Candidate in 9 Months
Preclinical Candidate Derived in 9 Months via AI Platform Kodexia
XtalPi (2228.HK), listed on the Hong Kong Stock Exchange, has finalized a preclinical candidate (PCC) for small interfering RNA (siRNA) targeting IgA Nephropathy (IgAN) in just 9 months using its proprietary AI platform, Kodexia. This compresses the typical R&D timeline—which usually takes over 2 years from initial target discovery to preclinical candidate derivation—to one-third, demonstrating the commercialization capabilities of its platform technology. By connecting a Generative AI-based molecular design model, physics-based first-principles calculations, and a robotics-automated laboratory in a closed-loop system, the company has simultaneously increased development speed and success probability. This marks a turning point in the re-rating of the company's valuation, shifting from a simple Software-as-a-Service (SaaS) provider to a biotech with its own pipeline.
Demonstrated Gene Silencing Efficacy Tens of Times Superior to Clinical-Stage Controls
In cell-based in vitro efficacy evaluations, this preclinical candidate achieved a subnanomolar half-maximal inhibitory concentration (IC50), demonstrating potent target gene silencing activity. Compared to two global control molecules currently in clinical development targeting the same pathway, the IC50 values were tens of times lower, inducing equal or superior inhibitory responses at significantly lower drug concentrations. This implies that the required dosage for efficacy is greatly reduced, preemptively mitigating potential off-target effects and in vivo toxicity risks. The company also secured Freedom to Operate (FTO) by using AI to identify new active sites that circumvent existing patent barriers and simultaneously optimize sequence-specific chemical modifications.
Proven Multi-Month Efficacy Duration and Improved Patient Compliance in Primate Models
In in vivo pharmacokinetic/pharmacodynamic (PK/PD) testing on non-human primates (NHP), target protein inhibition in the blood was stably maintained for several months after a single administration. This has secured potential as a best-in-class therapeutic that can significantly extend the dosing interval from 3 months to over 6 months for patients with chronic kidney disease who require repeated administration. Toxicity evaluations also demonstrated a wide safety margin, meeting the strict entry requirements of the kidney disease market, which demands both safety and convenience. The significant extension of the dosing interval serves as a key competitive advantage by maximizing patient adherence during long-term treatment and reducing healthcare costs.
Targeting the $10 Billion Nephropathy Market and Enhancing Global Licensing Value
IgA Nephropathy, affecting approximately 10 million people worldwide, is an intractable disease leading to glomerular inflammation and renal failure, with the global therapeutic market projected to expand to $11.6 billion by 2036. XtalPi has entered the competitive landscape with a differentiated modality—long-acting siRNA—following existing standard treatments such as Calliditas' Tarpeyo (budesonide), Travere's Filspari (sparsentan), and Novartis' Fabhalta (iptacopan). Leveraging its proven preclinical data, XtalPi plans to rapidly pursue Investigational New Drug (IND) applications. This demonstrated preclinical competitiveness will serve as a powerful lever in gaining an advantage in large-scale licensing-out (L/O) and co-development negotiations with global big pharma in the future.
The derivation of this preclinical candidate demonstrates the time- and cost-saving productivity of the AI platform by shortening the RNAi discovery period, which typically takes years, to just 9 months. In the IgA Nephropathy market, which is growing rapidly from $21.8 billion in 2025 to $116 billion by 2036, the company has secured best-in-class potential to extend dosing intervals to several months compared to existing standard treatments like Calliditas' Tarpeyo and Travere's Filspari. Notably, it has established technical superiority by demonstrating an IC50 tens of times lower than that of Alnylam's cemdisiran (a Phase 2 competitor targeting the same pathway) and superior durability in primates. This is expected to serve as a powerful valuation re-rating trigger, driving large-scale licensing-out deals with global big pharma around the Phase 1 clinical trials and partnerships for new target expansion.