Carmine is looking for novel modalities to replace viral-based gene therapies
CEO: XQ Lin
Based: Cambridge, Massachusetts
Clinical focus: Non-viral genetic medicines
The scoop: Drug developers will only be able to unleash the full power of gene therapies and nucleic acid therapies if they have effective drug delivery technologies. Viral vectors and lipid nanoparticles, the go-to options today, both have limitations, leading some groups to pin their hopes on exosomes. Yet, exosomes pose their own problems, creating an opportunity for Carmine Therapeutics to use its novel approach to establish itself as a next-generation, non-viral gene therapy company.
What makes Carmine Fierce: Carmine is working on vesicles with characteristics that read like a checklist for the ideal delivery vehicle. Potential for repeat dosing? Check. High transgene capacity? Check. Simple, scalable manufacturing? Check.
That checklist sets the delivery vehicles, called red blood cell extracellular vesicles (RBCEVs), apart from the existing options. Viral vectors have limited transgene capacity and immunogenicity issues that prevent repeat dosing. Lipid nanoparticles (LNPs) localize to the liver. Exosomes, which have emerged as a hotly tipped alternative to the established approaches, stand to eliminate those problems but may come with baggage of their own.
“Some current exosomes are fairly heterogeneous and usually require some sort of engineered cell line and cell culture to produce a sufficient quantity,” Carmine CEO XQ Lin said.
Carmine’s RBCEVs share some similarities with exosomes but are a distinct technology. Originating in the plasma membrane, RBCEVs are highly homogeneous and capable of carrying molecules up to the size of DNA plasmids. RBCEVs deliver “way in excess of 11 kb with high transduction efficiencies,” Lin said, and the long history of blood transfusions suggest they should be safe and redosable.
The vesicles also stand to be easier to manufacture. Carmine starts off with blood from blood banks and makes RBCEVs from it without any upstream cell culture or expansion steps. None of Carmine’s manipulations of RBCEVs happen at the cell source stage. Carmine has developed methods to modify the RBCEV surfaces, for example to attach targeting ligands, but those changes happen exogenously. Depending on the target, such modifications may be unnecessary.
“Naturally, RBCEVs go to interesting places that LNPs can't really get to. So, there's a potential to leverage natural tropism, but also to then optionally modify the surface,” Lin said.
Carmine is applying the technology to a couple of undisclosed lead indications with a view to getting into the clinic in the next few years. Takeda has also signed up to access the technology through a two-target deal worth up to $900 million in biobucks. Talk of inbound interest suggests more deals could be coming.
“A lot of pharmaceutical companies are looking for novel modalities to replace viral-based gene therapies,” Ronne Yeo, vice president, discovery at Carmine, said.
Takeda and existing investors participated in a seed-plus round earlier this year but Carmine already has one eye on its next raise. Lin expects to start pulling together a series A round around the end of the year, setting Carmine up to advance its lead programs while completing some of the work that will be needed to establish RBCEVs as a new modality.
Despite its early stage of development, Carmine is hiring and setting up a CMC group to get a head start on an area that has slowed some other startups down in recent years.
“With any kind of novel modality, this whole CMC characterization piece is quite important. So, we're getting a significant head start on that aspect of building up the assays and analytical methods that will be needed for characterizing such a first-in-class novel drug product,” Lin said.
Investors: Esco Ventures X and Takeda Ventures.