ABio Advances LANFA as a Next-Generation Alternative to PEG in Drug Delivery
核心洞察
ABio is developing LANFA (搜索), a novel water-solubilising agent designed to overcome PEG's limitations, including immune recognition and reduced delivery efficiency after repeated administration.
Preclinical studies show LNP-LANFA (搜索) improves the spleen-to-liver distribution ratio by approximately 3.3-fold compared with conventional LNPs, supporting potential vaccine and immunotherapy applications.
Binding LANFA (搜索) to paclitaxel increased water solubility more than 100,000-fold without requiring Cremophor EL/ethanol, potentially avoiding formulation-related hypersensitivity and CNS toxicity.
A Biotech Co. Limited (ABio) (搜索) is advancing LANFA (搜索), a novel water-solubilising agent positioned as a next-generation alternative to polyethylene glycol (PEG) (搜索) in drug delivery, alongside its LNP-LANFA lipid nanoparticle platform. In an interview with Koichi Yoshimi, CEO of A Biotech Co. Limited, the company detailed emerging preclinical data showing altered biodistribution compared with conventional LNPs, as well as applications in poorly water-soluble drugs, vaccines and cancer therapeutics.
Addressing PEG's Limitations in Drug Delivery
Drug delivery systems (DDS) are essential for safely encapsulating and transporting drugs to target sites in the body, and PEG has long been one of the most widely used substances for DDS applications. While PEG is relatively safe among water-solubilisation technologies, it can be recognised as a foreign substance in some individuals, potentially triggering an immune response. Repeated administration has also been shown to reduce drug-delivery efficiency.
To address these challenges, ABio developed LANFA (搜索) as a potential alternative to PEG, aiming to overcome limitations associated with PEG-containing delivery systems, including immune recognition and reduced delivery efficiency following repeated administration. "Our studies to date have generated encouraging preclinical results, and further studies are underway to characterise LANFA's immunogenicity, safety and delivery performance," Yoshimi said.
Combining LANFA (搜索) with lipid nanoparticles (LNPs), such as those used in mRNA vaccines, has the potential to enable efficient delivery of nucleic acids into immune cells, positioning LANFA as a potential new platform technology for drug delivery with the aim of improving biocompatibility and delivery performance.
Altered Biodistribution Favouring the Spleen
Preclinical studies demonstrated that LNPs incorporating LANFA (搜索) (LNP-LANFA) showed reduced liver distribution and a relative increase in distribution to the spleen. As a result, the spleen-to-liver distribution ratio improved by approximately 3.3-fold compared with conventional LNPs.
Yoshimi attributed this shift to the influence of LANFA (搜索) on the surface properties and pharmacokinetics of the LNPs. Conventional PEGylated LNPs often show substantial hepatic distribution following systemic administration, influenced in part by interactions with serum proteins such as apolipoprotein E (搜索). "Our results suggest that incorporating LANFA changes the biological interactions of the LNP surface, resulting in reduced relative liver distribution and increased relative splenic distribution. The precise mechanisms responsible for this shift are still under investigation," he said.
LANFA (搜索) also incorporates ester linkages designed to be more readily cleavable under biological conditions than the ether backbone characteristic of PEG, which may offer advantages in biodegradability. These properties are particularly significant for vaccines and immunotherapy, because the spleen contains a large number of immune cells. Enhanced delivery to splenic immune-cell populations could be advantageous for applications designed to induce or modulate immune responses, giving LNP-LANFA strong potential across nucleic acid therapeutics, including mRNA vaccines and cancer immunotherapy.
Preclinical Roadmap Toward Clinical Translation
ABio is finalising the next stage of its preclinical development programme and is in discussions with a pharmaceutical company that is a potential collaborative research partner. The company plans to conduct five studies this year: spleen cell analysis to evaluate and compare uptake and expression profiles of LNP-PEG and LNP-LANFA (搜索) in splenic immune cells; accelerated blood clearance (ABC) analysis to evaluate whether repeated administration alters pharmacokinetics or induces accelerated blood clearance; an in vivo distribution study using luminescence to compare expression patterns and tissue distribution of pDNA and other molecules; toxicity studies assessing hepatotoxicity, systemic adverse reactions and changes in major-organ weights; and cytokine measurement to assess immune response, inflammation and safety.
The results will help define subsequent IND-enabling studies, including more comprehensive toxicology, pharmacokinetic, biodistribution and CMC requirements in consultation with development partners and regulatory authorities.
Applications in Poorly Water-Soluble Drugs and Oncology
LANFA (搜索)'s inherent high water solubility and biocompatibility make it well suited to poorly water-soluble drugs, and ABio is exploring two complementary approaches. In the first, LANFA is chemically conjugated to poorly soluble drugs such as paclitaxel (PTX) to improve aqueous solubility. In the second, DMG-LANFA is used as a formulation component to disperse paclitaxel without chemically modifying the drug itself.
With paclitaxel, LANFA (搜索) achieved water solubilisation without requiring Cremophor EL/ethanol in the formulation. This could potentially avoid formulation-related adverse effects associated with Cremophor EL/ethanol, including hypersensitivity reactions and central-nervous-system toxicity, although this will need to be established in further preclinical and clinical studies. In water solubility evaluation experiments, binding LANFA to paclitaxel increased its water solubility more than 100,000-fold. ABio is also exploring other poorly water-soluble drugs and plans to conjugate LANFA to SN-38, a potent anticancer agent, to improve its solubility.
In an MTT assay, the DMG-LANFA (搜索) formulation demonstrated concentration-dependent cytotoxic activity, with cell viability decreasing to approximately 10% at higher concentrations. "These findings are encouraging, but further in-vivo studies will be required to determine pharmacokinetics, tolerability, tumour exposure and antitumour efficacy," Yoshimi noted.
LNP-LANFA (搜索) also shows strong potential as a next-generation DDS for solid tumours, with promise in a targeting approach that decorates the LNP surface with antibodies or peptides against cancer-specific antigens such as HER2 (搜索) and EGFR (搜索).
Partnership Strategy and Development Milestones
ABio held 37 meetings with pharmaceutical, biotech and research organisations at BIO USA 2026. The company envisions a flexible partnering model that may include non-exclusive licensing, molecule- or indication-specific licensing, co-development and sponsored research collaborations. An ideal partner would contribute complementary capabilities in formulation development, disease biology, CMC, regulatory development and clinical execution, while ABio contributes the LANFA (搜索) platform, formulation know-how and associated intellectual property.
For LNP-LANFA (搜索), ABio is seeking a joint development partnership with a pharmaceutical company that can lead next-generation vaccine development end to end, from formulation through preclinical and clinical trials, New Drug Application (NDA) submission, and on to market launch and sales.
For LANFA (搜索), the near-term focus in 2026 is completing nonclinical validation of PTX-LANFA and securing partnerships. In 2027, the company is targeting partner-funded joint development aimed at advancing PTX-LANFA toward IND-enabling development and eventual clinical evaluation. From 2028 onwards, ABio plans to extend the platform to further poorly water-soluble drugs such as SN-38 and to license its "regeneration platform for poorly soluble drugs" to multiple companies.
For LNP-LANFA (搜索), ABio completed initial proof-of-concept preclinical studies and filed patent applications covering multiple potential applications. An MOU with a major pharmaceutical company is scheduled to be signed in 2026, with the next objective being completion of additional preclinical studies to characterise immune-cell uptake, repeated-dose behaviour, biodistribution and safety. Subject to successful preclinical results, regulatory requirements and partnership progress, the target from 2027 is to advance into partner-led IND-enabling development, including CMC and toxicology programmes. In 2028 and beyond, ABio plans to reinvest revenue in expanding its LANFA-based solubility-enhancement platform and developing a next-generation LANFA-based LNP platform.