<div id="readability-page-1"><div> <div> Hu-mAtrIx™-Enabled Next-Generation ACVR2A/2B- Targeting Antibody Demonstrates Potential to Become a Best-in-Class Therapy for Obesity , /PRNewswire/ -- Harbour BioMed (the &#34;Company&#34;; HKEX: 02142), a global biopharmaceutical company committed to the discovery and development of novel antibody therapeutics in immunology, oncology and other disease areas, today announced preclinical data for LET003, its first next-generation ACVR2A/2B-targeting monoclonal antibody developed using the Hu-mAtrIx™ platform. The results showed that LET003 exhibited superior pharmacokinetic characteristics compared to multiple competitor molecules. When combined with semaglutide, LET003 significantly enhanced fat reduction while effectively preserving lean mass. In addition, LET003 achieved lean mass-promoting effects at lower dose level comparable to bimagrumab at higher dose level, highlighting its potential to become a best-in-class therapy for obesity treatment. The ACVR2A/2B signaling pathway plays a critical role in regulating the balance between fat and muscle mass in the body. Previously, bimagrumab, the first antibody targeting ACVR2A/2B, demonstrated positive clinical results, showing favorable efficacy and safety in combination with semaglutide for obesity treatment. Building on these findings, Harbour BioMed successfully advanced the molecular optimization and functional enhancement of LET003 through structure biology and Hu-mAtrIxTM, its AI platform-driven antibody engineering approaches. In human FcRn transgenic mouse and cynomolgus monkey models, researchers compared the blood clearance rates of LET003 with several competing molecules following subcutaneous administration. Results showed that LET003 exhibited significantly slower clearance than all comparator molecules tested, suggesting that it may achieve comparable efficacy with longer dosing intervals or lower doses relative to competing therapies. In an obesity model using wild-type mice, semaglutide (30 nmol/kg) and LET003 (20 mg/kg) were administered subcutaneously once weekly as monotherapies or in combination. Results after three weeks of treatment showed: <ul type="disc"> <li>LET003 in combination with semaglutide decreased fat mass by 76.0% compared with vehicle (P&lt;0.0001), and by 34.7% compared with semaglutide monotherapy (P&lt;0.0001).</li> <li>In the combination group, lean mass decreased by 6.5% compared with vehicle (P=0.0001), but increased by 5.7% compared with semaglutide monotherapy (P=0.0007).</li> </ul> These data suggest that combining LET003 with semaglutide can significantly enhance fat reduction while effectively mitigating the lean mass loss associated with semaglutide treatment alone. In a high-fat diet-induced obesity model using human FcRn transgenic mice, semaglutide (30 nmol/kg) and LET003 (20 mg/kg) were administered subcutaneously once weekly as monotherapies or in combination. Results after three weeks of treatment showed: <ul type="disc"> <li>The fat-to-body weight ratio in the combination group was reduced by 17.5% compared with vehicle (P&lt;0.0001), and by 6.0% compared with semaglutide monotherapy (P=0.0127).</li> <li>The lean mass-to-body weight ratio in the combination group was increased by 15.2% compared with vehicle (P&lt;0.0001), and by 5.3% compared with semaglutide monotherapy (P=0.0194).</li> </ul> These data further confirm that combining LET003 with semaglutide not only more effectively reduces body fat proportion, but also significantly improves lean mass ratio, enabling superior body composition management. In a separate study using human FcRn transgenic mice maintained on a normal diet, mice received weekly subcutaneous injections of LET003 or a comparator molecule at 20 mg/kg. After three weeks of treatment, both molecules induced an increase in lean mass and a consequent increase in overall body weight. Specifically: <ul type="disc"> <li>The LET003 treatment group showed an 18.3% increase in lean mass compared with vehicle (P&lt;0.0001), and a 13.5% increase compared with the comparator molecule (P&lt;0.0001).</li> <li>The LET003 treatment group showed an 11.1% increase in overall body weight compared with vehicle (P &lt; 0.0001), and a 9.3% increase compared with the competitor molecule (P &lt; 0.0001).</li> </ul> These findings suggest that LET003 is superior to the competitor molecule in promoting lean mass. In another study using human FcRn transgenic mice maintained on a normal diet, mice received weekly subcutaneous injections of bimagrumab or LET003 at different dose levels (5 mg/kg, 10 mg/kg, and 15 mg/kg). The results showed that both molecules contributed more to the increase in lean mass than to fat accumulation. After three weeks of treatment, LET003 at 5 mg/kg achieved lean mass-promoting effects comparable to those observed with 15 mg/kg bimagrumab. These results suggest that LET003 can achieve lean mass-promoting effects at lower dose level comparable to bimagrumab at higher dose level, demonstrating its excellent pharmacological potential. &#34;The rapid advancement of LET003 has been strongly supported by our Hu-mAtrIx™ AI platform. Built on data generated from our proprietary Harbour Mice® platforms, Hu-mAtrIx™ integrates fine-tuned large language models for sequence generation together with highly accurate AI classification and developability prediction models,&#34; said Dr. Jingsong Wang, Founder, Chairman and Chief Executive Officer of Harbour BioMed. &#34;We are highly encouraged by the favorable pharmacokinetic profile demonstrated by LET003 in preclinical studies, as well as its potential in fat reduction and lean mass preservation. These findings further validate our technological capabilities in AI-driven antibody engineering and metabolic disease research. We look forward to rapidly advancing LET003 into clinical development and providing obesity patients worldwide with more effective and safer treatment options.&#34; About LET003 LET003 is a potential best-in-class next-generation monoclonal antibody targeting activin receptors ACVR2A and ACVR2B. ACVR2A and ACVR2B play critical roles in regulating muscle-fat metabolic homeostasis. Extensive preclinical and clinical studies have demonstrated that combining receptor-blocking antibodies targeting ACVR2A/2B with GLP-1-based weight loss therapies can further reduce body fat while effectively mitigating lean mass loss. LET003 is the first ACVR2A/2B dual-target blocking antibody developed using the Hu-mAtrIx™ artificial intelligence platform. It has demonstrated superior pharmacokinetic properties compared with several competing molecules and, in preclinical animal models, has shown enhanced fat reduction and lean mass preservation effects when used in combination with GLP-1 therapies. About Harbour BioMed Harbour BioMed (HKEX: 02142) is a global biopharmaceutical company committed to the discovery and development of novel antibody therapeutics in immunology, oncology and other areas. The Company is building a robust portfolio and differentiated pipeline through internal R&amp;D capability, strategic global collaborations in co-discovery and co-development, and selective acquisitions. Our proprietary antibody technology platform, Harbour Mice®, generates fully human monoclonal antibodies in both the conventional two heavy and two light chain (H2L2) format and the heavy chain-only (HCAb) format. Building upon HCAb antibodies, the HCAb-based immune cell engagers (HBICE®) bispecific antibody technology enables tumor-killing effects that traditional combination therapies cannot achieve. The HCAb-based Antibody Plus technology (HCAb PLUSTM) provides comprehensive modality solutions for the development of innovative multi-specific medicines in different disease areas. Additionally, building upon the Harbour Mice® platform, Harbour BioMed launched its first fully human Generative AI HCAb Model powered by its Hu-mAtrIxTM AI platform, accelerating the development of innovative therapies. By integrating Harbour Mice®, HBICE®, HCAb PLUSTM, a single B-cell cloning platform and AI technologies, Harbour BioMed has built a highly efficient and distinctive antibody discovery engine for developing next-generation therapeutic antibodies. For more information, please visit www.harbourbiomed.com. SOURCE Harbour BioMed <img src="https://imageproxy.pbkrs.com/https://rt.prnewswire.com/rt.gif/query-RGF0ZUlkPTIwMjYwNTE3Jk5ld3NJdGVtSWQ9Q042MTM0MCZUcmFuc21pc3Npb25fSWQ9MjAyNjA1MTcyMDAzUFJfTkVXU19VU1BSX19fX19DTjYxMzQw?x-oss-process=image/auto-orient,1/interlace,1/resize,w_1440,h_1440/quality,q_95/format,jpg" original-src="https://imageproxy.pbkrs.com/https://rt.prnewswire.com/rt.gif/query-RGF0ZUlkPTIwMjYwNTE3Jk5ld3NJdGVtSWQ9Q042MTM0MCZUcmFuc21pc3Npb25fSWQ9MjAyNjA1MTcyMDAzUFJfTkVXU19VU1BSX19fX19DTjYxMzQw"/></div> </div></div>

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Harbour BioMed announced promising preclinical data for LET003, its first AI-enabled drug candidate targeting obesity. LET003 demonstrated superior pharmacokinetics and enhanced fat reduction when combined with semaglutide, while preserving lean mass. The results suggest LET003 could be a best-in-class therapy for obesity, achieving significant fat loss and lean mass improvement at lower doses compared to competitors. The findings were supported by the company's Hu-mAtrIx™ AI platform, indicating strong potential for future development.

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20:03 ETHarbour BioMed Announces Promising Preclinical Data for LET003, Its First AI-Enabled Drug Candidate