small makes large molecules more powerful

• Nanoform’s technology enables the development of highly concentrated (>400 mg/ml), stable formulations of biologics for subcutaneous administration, providing a step-change improvement over current standards of care
• This innovation makes administration of biologics more accessible; improving patient adherence, therapeutic outcomes, and lowering healthcare system costs.

Biologic therapies have been demonstrated to be well tolerated and targeted, and can significantly improve patient outcomes. However, their administration presents challenges due to aspects of their intrinsic nature, such as their high molecular weight, physical and chemical instability, and susceptibility to enzymatic degradation.

Most biologics are administered intravenously (IV), as it is the quickest way to achieve target drug levels in the blood. Administration by IV, however, typically requires clinical administration with high costs on the healthcare system and treatment burden for patients. Subcutaneous (SC) delivery has emerged as an attractive alternative, offering opportunities for self-administration at home, improving the patient’s experience, reducing the need for hospital visits and increasing adherence.

However, formulations of large molecules for SC administration are challenging to develop, as therapeutic doses are frequently greater than 1,000 mg and the volume that can be administered subcutaneously is limited, because the drug load and composition with excipients impact the drug’s syringability and injectability (most biologic molecules have an exponential relationship between concentration and viscosity). Consequently, effective protein concentrations are rarely beyond 120 mg/ml.

Our approach is to use protein suspensions consisting of nano- to micron-sized particles dispersed in a non-aqueous vehicle, with shear thinning enabling low injection forces. Particle size, polydispersity, and morphology are controlled to ensure injectability.

Read more about our trastuzumab suspension case study here.

Direct manufacturing of peptide/protein particles in the appropriate size range with optimal fine particle fraction and dose delivered.

Inhaled delivery of biological therapies is an evolving field with potential as a new route of administration.

Nanoform’s Biologics platform uses nebulization to form droplets and drying gas at room temperature to remove water, which imparts less stress on sensitive drugs. The formation of protein aggregates in Nanoform Biologics lines is low, and the process produces particles that can be directly utilized for inhaled delivery:

• the particle size and aerosolization properties can be tuned to target lung tissues in either the upper or lower respiratory tract
• improvements have been seen in the fine particle fraction (90%) compared to conventional technologies such as spray drying (50%)
• compatibility with a wide range of dry powder inhalers
• high drug load enabling high doses

An alternative option to the inhaled dry powder can be the formulation of nanoparticles into nanosuspensions suitable for nebulization.

To deliver large molecule therapeutics (peptides and proteins) to the lung in a dry powder inhaler (DPI) can be challenging due to the isolation of the materials in dry powder form. Many larger molecules are sensitive to drying techniques such as spray drying or lyophilization, which can cause instability and decrease activity of the molecule post processing. Nanoform’s Biologics platform can successfully produce nano- to low-micron sized particles in a gentle way, which maintains excellent physical stability and biological effectiveness of the powders post processing. Recent work conducted with Takeda showed superior delivery in vivo of plasma derived therapies delivered as dry powders by Nanoforming vs Spray Drying.