Lipid Licensing

Access to formulation expertise and proprietary lipid library to streamline drug development

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Overview

Safe and effective delivery of mRNA into target cells offers promising therapeutic possibilities. Ionizable lipid-based nanoparticles represent one of the most advanced nonviral vectors for efficient delivery of nucleic acids.

Ionizable lipid design can influence LNP encapsulation efficiency, biodistribution, and therapeutic effects. Fujifilm has designed and characterized a wide array of lipid molecules to accelerate synthesis and empower advanced research and drug development.

Fujifilm’s proprietary ionizable lipids are amphiphilic molecules with a polar diamine head group, a hydrophobic tail region, and a biodegradable linker between the two. Mixing and matching these different components can fine-tune the lipophilicity, bulkiness, and pKa of the nanoparticle.

Lipid Library

Ionizable Lipids

Ionizable lipids remain neutral at physiological pH and are protonated in acidic conditions. As key components of LNPs, ionizable lipids promote membrane destabilization and facilitate endosomal escape to improve biocompatibility and reduce toxicity.

Learn more about Fujifilm’s CDMO services for LNP formulation development using proprietary ionizable lipids.

Fujifilm has designed and characterized over 500 different ionizable lipids, many of which exceed benchmarks in in vivo mRNA delivery studies.

As we continue to build and expand our lipid library, we offer CDMO services and out-licensing to LNP formulation development partners.

Fujifilm has identified novel ionizable lipids through in vivo screening of over 500 compounds, of which more than 30% exceed the mRNA delivery benchmark.
Table of FUJIFILM’s proprietary ionizable lipids for customers. FL-2266 and FL-0445 are patented and available in GMP grade. These can be suitable for use in siRNA, mRNA, and pDNA applications. FL-0207T, FL-0179T, FL-1252T and FL-1207T can be applicable to mRNA. , while FL-1923T can be suitable for pDNA applications.

Proprietary Ionizable Lipids

These candidate lipids show improved efficiency and biodistribution and comparable safety compared to commercially available LNPs in various application studies.

Application Studies

Type-A lipids

Prophylactic immunization with Fujifilm Type-A LNP induces anti-tumor immunity

C57BL/6J mice (N=8 per group) were treated with OVA mRNA (TriLink, CleanCap®) encapsulated in FL-0445 via IM injection weekly for 3 weeks (Day -21, -14, -7), positive control (OVA protein/adjuvant mixture) via SQ injection weekly for 3 weeks (Day -21, -14, -7), or vehicle. Tumor (4 × 105 E.G7-OVA cells) was implanted SQ on Day 0.

Tumor volume and percentage of tumor-free mice post implant were comparable to positive control levels.

Treatment with FL-0445 encapsulating OVA mRNA inhibits tumor growth as efficiently as an OVA protein/adjuvant mixture used as a positive control.
The percentage of tumor-free mice after FL-0445 treatment was comparable to positive control levels.
FL-0207T and FL-0179T induce human erythropoietin expression at levels comparable to those of the commercially available Lipid-5 for up to 6 hours after dosing. Approximately 1.5-fold higher induction is observed 24 and 48 hours after dosing with FL-0207T and FL-0179T compared to Lipid-5.
FL-0207T and FL-0179T are retained in blood for at least 48 hours, whereas  Lipid-5 has almost disappeared after 24 hours.

Type-B lipids

Fujifilm LNPs induce higher protein expression and improve PK profiles in nonhuman primates

Cynomolgus monkey (male, 4 y, N=2) were treated with human erythropoietin (hEPO) mRNA encapsulated in Lipid-5, FL-0207T, or FL-0179T (0.2 mg/kg, 1 h, IV infusion).

Fujifilm’s FL-0207T and FL-0179T LNPs induced higher hEPO expression due, at least in part, to improved circulation times.

Type-B lipids

No hepatotoxicity concerns were observed with Fujifilm LNPs

SD rats (female, 6 wks, N=3) were treated with a single dose of hEPO mRNA encapsulated in Lipid-5, FL-0207T, FL-0179T (1 mg/kg, IV infusion), or vehicle.

No significant increases in AST and ALT — markers of hepatotoxicity — were observed.

Plasma levels of AST and ALT are comparable upon treatment with vehicle, Lipid-5, FL-0207T, and FL-0179T.
Intramuscular or intradermal administration of pDNA  via FL-1932T results in approximately 9-fold  or 3-fold higher antigen-specific IgG expression at 11 weeks, respectively, compared to adjuvant + pDNA treatment.

Type-D lipids

Fujifilm LNPs deliver pDNA and induce IgG production

Rabbits (N=2) were treated with LNP-encapsulated pDNA (FL-1923T, 0.2 mg/head, IM and ID) or pDNA/adjuvant mixture.

Rabbits treated with Fujifilm LNPs expressed antigen-specific IgG.

FUJIFILM LNP exposure results in approximately 1.5-fold increased ex vivo TCR knockout efficiency in activated T cells compared to benchmark levels.

Ready-to-use LNP for ex-vivo gene editing in T cells

Fujifilm LNPs show higher endogenous T cell receptor (TCR) knockout efficiency in activated T cells than benchmark.

This ready-to-use LNP formulation is available to customers.

Efficient transfection in primary human T cells cultured ex vivo

Fujifilm has identified LNP formulations that exhibit both improved cell proliferation and performance beyond benchmark LNP when transfected into primary T cells.

FUJIFILM LNP results in improved transfection of GFP mRNA into activated T cells compared to benchmark. Total cell yield on day 8 was 103% and 106% for Fujifilm LNP at 6.24 μg and 1.56 μg per million cells, respectively, compared to 95% for benchmark at 6.24 μg per million cells.