Next-generation Therapeutic Antibodies & Vascular Targeting

Most biotech companies involved in the development of antibody-based drugs rely on the intact immunoglobulins (“IgG”) to inhibit a target molecule or to mediate the killing of target cells thanks to the action of the antibody’s constant region (“Fc”) on macrophage and NK cells.

IgG-based therapeutics typically exhibit an excellent tolerability profile, but frequently fail clinical development programs due to lack of activity.

 It is becoming increasingly recognized that IgG-based pharmaceuticals may suffer from fundamental limitations:

a) if the antibody aims at blocking a target molecule (e.g., a soluble factor which promotes tumor growth), the antibody will not be very efficacious (or not efficacious at all) if the target molecule is not the SOLE cause of disease.

Even if antibodies target biologically important targets (e.g., Avastin blocking VEGF-A), the therapeutic efficacy is typically minimal.

b) if the antibody aims at decorating target cells with the antibody’s Fc portion, thus activating immune cells and complement, the efficacy will be minimal for certain disease areas (e.g., eradication of solid tumors), since therapeutic IgG products are typically blocked by antigen on perivascular target cells and cannot homogenously distribute within the disease mass, even at very high doses.

Philogen has recognized the limitations of conventional IgG-based therapeutics and has worked for over 10 years on the development of next-generation antibody-based therapeutics.

Philogen's products rely on the antibody-based delivery of bioactive molecules to vascular sites of disease (Vascular Targeting). Importantly, this approach may result in the improvement of the therapeutic index of medicinal agents which are already present on the market, or which have been investigated as non-targeted drugs and have failed because of insufficient selectivity.

PROBLEMS OF CONVENTIONAL IgG’s THERAPEUTICS

• limited efficacy when the antibody target antigen is not the sole cause of disease
• limited tissue distribution within disease (e.g., within the tumor mass), due to the IgG size and to antigen barrier on perivascular cells, thus limiting therapeutic activity
• high cost of goods (typically hundreds of milligrams per patient)
• selection of antigen-negative variants by tumor cells (IgG does not work on those cells)

BENEFITS OF PHILOGEN’S ANTIBODY THERAPEUTICS & VASCULAR TARGETING

• targeted delivery of established drugs maximize their potential (increase potency, less damage to normal organs)
• superior biodistributions, as markers of angiogenesis are well accessible to biopharmaceuticals coming from the bloodstream
• low cost of goods (typical doses in the low milligrams range per patient)
• genetic and chemical stability of vascular targets (e.g., splice isoforms of fibronectins and tenascins), thus preventing resistance mediated by chromosomal instability of tumor cells.