AM-710 is an ultra-long-acting prodrug of orforglipron, with >150-fold half-life extension, enabling once every 3 month and once every 6 month dosing or longer
A single subcutaneous dose of AM-710 produced and maintained >15% weight loss in hGLP1R diet-induced-obese (DIO) mice over a one-month study period
AM-710 treatment produced greater, sustained improvements in fasting blood glucose, oral glucose tolerance testing, weight loss and fat mass loss versus daily oral orforglipron
Aion Medicines, a subsidiary of Exavir Therapeutics, announced the presentation of preclinical data for AM-710, the company's ultra-long-acting small molecule GLP1R agonist, at the ObesityWeek conference in Atlanta, GA demonstrating the potential for a best-in-class profile and multi-month dosing intervals.
"These impressive data demonstrate that AM-710 is a unique and highly differentiated compound in a complex and evolving landscape," said Tim Garnett, former Chief Medical Officer of Eli Lilly and Company, and scientific advisor to Aion Medicines. "We have seen how the shift from daily to weekly incretin agents, like Wegovy and Zepbound, has transformed patient outcomes with pharmacokinetic enhancement. Aion's next generation half-life extension stands to deliver the next leap in tolerability, efficacy, adherence and outcomes for the class."
The presentation, titled "Preclinical characterization of AM-710, a novel ultra-long-acting small-molecule GLP1R agonist," detailed in vivo pharmacokinetic and pharmacodynamic studies of AM-710, a prodrug of orforglipron selected from Aion's library of proprietary half-life extended small molecule GLP1R agonist prodrugs.
- PK studies conducted in mice and rats showed apparent half-life of 76-91 days, representing an >150-fold half-life extension versus oral orforglipron dosing, and favorable PK parameters, including reduced Cmax and prolonged Tmax, that are pertinent to GLP-1 receptor agonist tolerability.
- PD studies conducted in humanized GLP1R diet induced obesity (DIO) mice over a 4 week period compared single subcutaneous injections of AM-710 (low dose and high dose) versus 2 weeks of daily oral orforglipron or vehicle control followed by two weeks of recovery.
- Both single dose AM-710 groups produced profound food intake suppression, body weight loss, fat mass loss, fasting blood glucose reduction and improved oral glucose tolerance throughout the study period.
- At Week 2, a single injection AM-710 low dose and 15 days of oral orforglipron showed similar weight loss, but AM-710 low dose produced greater fat mass loss, indicating a potential beneficial effect of AM-710 on body composition. AM-710 high dose produced the greatest weight loss (>-15%) and body fat reduction (>-25%) of all groups.
- At Week 4, both single dose AM-710 groups sustained weight loss, fat mass reduction and glycemic control, but oral orforglipron animals rebounded in all PD parameters following 2 weeks of recovery to similar level to that of the vehicle group that received no active treatment.
- Results from this study compare favorably to previously reported results of daily subcutaneous semaglutide injections at clinically relevant doses (30nmol/kg) in the same hGLP1R DIO mouse model, with greater weight loss reported in the current study for a single dose of AM-710 than for daily semaglutide over a one-month period.
"We are excited to share these promising data on AM-710 that support the potential for ultra-long-acting dosing intervals of every 3 to 6 months or longer. While competing agents have shown encouraging results with daily dosing in rodent models, we have demonstrated profound, sustained pharmacodynamic effects for over a month after a single dose of AM-710," said Brian Kearney, Chief Scientific Officer of Aion Medicines. "As a small-molecule prodrug of orforglipron, AM-710 is well-positioned to quickly advance through development and expand global access to GLP-1RA therapy with a scalable, well-tolerated, and infrequently administered treatment option for patients."
About Aion Medicines
Aion Medicines is a San Francisco, CA based biopharmaceutical company focused on discovering and developing ultra-long-acting medicines enabled by next generation pharmacology. Aion's platform delivers profound half-life extension, producing extended dosing intervals while reducing peak exposure and increasing trough exposure. For more information, please visit www.aionmedicines.com.
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