XtalPi AI Drug Discovery Collaboration Reaches Milestone as PharmaEngine's Novel PRMT5 Inhibitor PEP08 Receives Clinical Trial Approvals
SHENZHEN, China, Sept. 9, 2025 /PRNewswire/ -- XtalPi Inc. (Stock Code: 2228.HK) has announced that PEP08, a next-generation PRMT5 inhibitor candidate developed through its AI drug discovery collaboration with PharmaEngine, Inc. (TWO:4162), has received regulatory clearances to initiate Phase 1 clinical trials in solid tumors. Approvals include Australia's Human Research Ethics Committee (HREC), recognized by the Australian Therapeutic Goods Administration (TGA), and the food and drug authority of the Taiwan region (TFDA). This milestone triggered a payment to XtalPi under the partnership agreement.
PRMT5 (Protein Arginine Methyltransferase 5) is a validated synthetic lethality target in tumors harboring homozygous MTAP deletion, which is related to poor prognosis and present in 10-15% of human cancers, including small cell lung cancer (NSCLC), mesothelioma, pancreatic cancer, glioblastoma multiforme (GBM), head and neck cancer, esophageal cancer, and bladder cancer. While PRMT5 inhibition offers a potent mechanism for targeted therapy, first-generation inhibitors face significant challenges in selectivity, resulting in dose-limiting toxicities and unmet medical needs.
Leveraging its integrated drug discovery platform that combines quantum physics, AI, and large-scale robotic experiments, XtalPi partnered with PharmaEngine's scientific team to conduct de novo drug design. The AI platform generated a multi-million compound library for PRMT5, identifying novel lead series with exceptional potency and selectivity. Following iterative optimization through quantum physics and AI-powered ADMET screening, PEP08 emerged as the preclinical candidate (PCC) and advanced through IND-enabling studies by PharmaEngine.
As a second-generation PRMT5 inhibitor with a novel scaffold, PEP08 demonstrates superior activity and selectivity. Its MTA-cooperative binding mode stabilizes a ternary complex with PRMT5, enabling highly selective target inhibition. This mechanism drives potent synthetic lethality efficacy against MTAP-deleted tumor cells while minimizing off-target effects on normal cells, highlighting significant therapeutic potential.
Preclinical studies revealed PEP08's markedly improved safety profile compared to first-generation PRMT5 inhibitors, alongside favorable blood-brain barrier penetration and overall developability characteristics. The compound achieved robust in vivo efficacy across multiple animal models. Compared to other clinical-stage second-generation candidates, PEP08 exhibits potential best-in-class properties and compelling combination therapy opportunities. PharmaEngine presented these findings at the 2025 American Association for Cancer Research (AACR) Annual Meeting.
PEP08's successful regulatory clearance and milestone achievement underscore XtalPi's platform-driven innovation capabilities and mark a pivotal advancement in its partnership with PharmaEngine. XtalPi remains committed to empowering partners to discover novel drug candidates addressing complex targets, accelerate the development of competitive pipeline projects, and deliver transformative medicines to patients worldwide.
About PharmaEngine, Inc.
PharmaEngine, Inc., headquartered in Taipei, began operations in February 2003. PharmaEngine focuses on new drug development by adopting "Virtual Pharmaceutical Company Business Model". PharmaEngine has one commercial product, ONIVYDE®, which is currently approved in most major markets including the U.S., Europe, and Asia in combination with fluorouracil and leucovorin for the treatment of adult patients with metastatic pancreatic adenocarcinoma after disease progression. PharmaEngine also conducts, collaborates or licenses-in new drug discovery and development projects. With extensive experience in drug development and project management, PharmaEngine continues to expand the pipeline and accelerate drug development and the subsequent commercialization of new medicines.
About XtalPi
XtalPi Holdings Limited (XtalPi, 2228.HK) was founded in 2015 by three physicists from the Massachusetts Institute of Technology (MIT). It is an innovative R&D platform powered by quantum physics, artificial intelligence, and robotics. By integrating first-principles calculations, AI algorithms, high-performance cloud computing, and standardized automation systems, XtalPi provides digital and intelligent R&D solutions for companies in the pharmaceutical, materials science, agricultural technology, energy, new chemicals, and cosmetics industries.
SOURCE XtalPi Inc.
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