- MB-111 is a potential first-in-class, single-dose in vivo CRISPR gene editing therapy for persistent chylomicronemia
- Oral presentation highlights safe, robust, and durable reduction of apoC-III and triglycerides by MB-111 in animal models
BRISBANE, Calif.--(BUSINESS WIRE)--#CRISPR--Mammoth Biosciences, Inc., a biotechnology company harnessing its proprietary next-generation in vivo CRISPR gene editing platform to create potential one-time curative therapies, today announced new preclinical data on its first clinical development candidate, MB-111, to be presented at the European Society of Gene & Cell Therapy (ESGCT) 32nd Annual Congress in Seville, Spain, on October 8, 2025.
MB-111 leverages CasPhi – a proprietary ultracompact CRISPR nuclease that is significantly smaller than Cas9-based systems. Encapsulated and delivered within a lipid nanoparticle along with the gRNA, MB-111 disrupts the expression of the APOC3 gene – a key regulator of triglyceride metabolism – in the liver.
Persistent chylomicronemia is a metabolic disorder characterized by extremely elevated triglyceride levels (>1000 mg/dL), resulting in recurrent and potentially life-threatening episodes of acute pancreatitis. MB-111 offers a potentially one-time, curative intervention aimed at lowering high triglyceride levels in affected patients.
The oral presentation shows that MB-111 substantially reduced APOC3 gene expression and disrupted apoC-III protein production in multiple animal models, further supporting its continued development for clinical use. The findings from this presentation include:
- In a humanized transgenic mouse model of hypertriglyceridemia, MB-111 administration led to substantial reductions in apoC-III protein and serum triglyceride levels.
- In nonhuman primates (NHPs), MB-111 administration resulted in saturating liver editing and sustained reductions in serum apoC-III protein.
- MB-111 administration was well tolerated in NHPs, with only transient elevations in liver function tests at higher dose levels.
“Our data showcase the strong foundation we envisioned when developing MB-111,” said Trevor Martin, Ph.D., co-founder and chief executive officer of Mammoth Biosciences. “With the ability to safely and effectively reduce apoC-III protein in NHPs and triglycerides in mouse models that closely reflect the diseases of hypertriglyceridemia, we see a clear line of sight towards the clinic in 2026 and, ultimately, to transforming care for patients who currently have limited options.”
Presentation Details
Title: Highly efficient lowering of serum APOC3 and triglyceride levels using an engineered CasΦ nuclease in NHPs and a mouse model of severe hypertriglyceridemia as basis for treatment of persistent chylomicronemia in humans
Speaker: Sean Chen, Ph.D., associate director, liver therapeutics, Mammoth Biosciences
Date and Time: Thursday, October 8, 2025, 16:30 CEST
Location: European Society of Gene & Cell Therapy 32nd Annual Congress, Seville, Spain
Fibes, Room Parallel A, Session 9a: Gene Editing II
More information about the oral presentation and conference may be found on the ESGCT meeting website.
About Mammoth Biosciences
Mammoth Biosciences is a biotechnology company focused on leveraging its proprietary ultracompact CRISPR systems to develop potential long-term curative therapies for patients with life-threatening and debilitating diseases. Founded by CRISPR pioneer and Nobel laureate Jennifer Doudna and Trevor Martin, Janice Chen, and Lucas Harrington, the company’s ultracompact systems are designed to be more specific and packageable to enable in vivo gene editing in difficult to reach tissues utilizing both nuclease applications and new editing modalities beyond double stranded breaks, including base editing, reverse transcriptase editing, and epigenetic editing. The company is building out its wholly owned pipeline of potential in vivo gene editing therapeutics and capabilities and has partnerships with leading pharmaceutical and biotechnology companies to broaden the reach of its innovative and proprietary technology platform. Mammoth Biosciences’ deep science and industry experience, along with a robust and differentiated intellectual property portfolio, have enabled the company to further its mission to transform the lives of patients and deliver on the promise of CRISPR technologies.
For more information, please visit www.mammoth.bio or follow Mammoth on LinkedIn or X.
Contacts
Media Contact:
Mohana Ray
Email: Mammoth.PR@hdmz.com
Phone: 312-506-5210
