Further Therapeutic Opportunities

The company’s GigaGen group discovers antibody drug candidates with unique profiles against several relevant, clinically validated oncology targets. Its lead drug candidates, GIGA-564 and GIGA-2328, bind a key oncology protein called CTLA-4. But instead of blocking CTLA-4 activity like most currently available anti-CTLA-4 drugs, they lead to reduced inhibition of the target, which in non-clinical models enhances anti-tumor efficacy while limiting drug toxicities. They induce depletion of T regulatory cells in the tumor microenvironment, enhancing the ability of the immune system to fight cancer.^1-2

Grifols is also investigating the potential of small molecules to block the action of detrimental plasma proteins to treat neovascular age-related macular degeneration (nAMD), the leading cause of blindness in people over the age of 60 in developed countries.

Furthermore, the company is collaborating with Selagine, Inc., to investigate the use of immunoglobulin eye drops in treating dry eye disease (DED), a condition affecting more than 100 million people globally. In a pilot phase 1/phase 2 clinical trial, Selagine treated subjects with eye drops based on Grifols Flebogamma DIF® twice daily for eight weeks and secured a significant reduction in the signs and symptoms of DED, and with no difference in tolerability or adverse events. This line of research contends that the broad-spectrum anti-inflammatory actions of an ocular surface immunoglobulin are superior to currently approved therapies, which are narrow spectrum and limited mainly to targeting T-cell inflammatory mechanism.

Our small molecule in development is an oral pill, AKST4290, which blocks the activity of a key circulating inflammatory protein called eotaxin, elevated in people with aging-related diseases.³

In a Phase 2 study in patients with nAMD treated with oral AKST4290, there was improvement in best corrected visual acuity, similar to the standard of care.

Our Alkahest group is developing an extracorporeal device that connects to standard hemodialysis machines, which can be designed to remove compounds associated with the development of different diseases to enhance health. 

Grifols’ first program in this category, AKST1210, is being advanced to potentially slow progression of cognitive impairment, with the hopes of enabling patients undergoing hemodialysis for end-stage renal disease (ESRD) to achieve improved treatment outcomes.

AKST1210 is believed to enable removal of beta-2 microglobulin (B2M), a protein in human plasma that increases in concentration with age and accumulates in the blood of ESRD patients undergoing hemodialysis. B2M was identified as a detrimental pro-aging factor with negative impacts on cognition and the generation of new neurons in the adult brain.⁴
 

We are exploring the potential use of fibrin sealant, a plasma-derived hemostat consisting of the blood-clotting proteins fibrinogen and thrombin, for tissue engineering and the production of a 3D printed bone substitute to address long-bone fractures due to their inability to heal correctly. Grifols’ tissue engineering strategies represent an important push into plasma-premised personalized medicine.