MNTF Discovery | GM6 Development | GM6 and the Blood-Brain-Barrier
GM6 Efficacy in Neuroprotection | Drug Properties | Pipeline

Neurodegenerative diseases and disorders are complex, multifactorial conditions, and multiple biologic targets must be modulated to affect the disease in question.

It is not surprising, then, that the current paradigm of single-target drug development continues to result in clinical trial failures with respect to neurodegenerative conditions. And yet for all this complexity, there is a considerable overlap of common pathways and targets across neurodegenerative diseases. It therefore stands to reason that something that could regulate these common underlying pathways and targets could have dramatic effects across a range of neurodegenerative conditions.

MNTF Discovery

Building on this core hypothesis, Genervon discovered what it believes is the naturally occurring regulator of the development of the human nervous system, called the “motoneuronotrophic factor” (MNTF), which is endogenously expressed at its highest levels at week nine of fetal gestation and remains detectable at very low levels in adult tissue. Extensive preclinical testing over many years suggests that MNTF regulates multiple key CNS-related biological functions—including neuronal differentiation, axonal regeneration, reinnervation, and inflammation and apoptosis—providing both neuroprotective and neuro-regenerative therapeutic effects. 

MNTF neurotrophin.png
MNTF expression.png

GM6 Development

Development of GM6, an Innovative First-in-Class Pleiotropic Peptide with Broad CNS Potential

  • GM6 is a 6-amino-acid peptide and an active analog of the endogenous embryonic stage regulator MNTF.

  • GM6 is able to rapidly transit the human blood-brain barrier given its small size and molecular weight.

  • GM6 has been shown to be safe and well-tolerated in a Phase 1 study, multiple Phase 2A studies, and compassionate use.

  • GM6 is non-mutagenic and does not inhibit typical CYP isoforms or interact with tPA.

  • GM6 is manufactured at low cost through solid-phase synthesis under GMP. 

  • GM6 is stable for 120 months at -20°C and 69 months at 5°C.

GM6 development.jpg
 

GM6 and the Blood-Brain-Barrier

GM6 RAPIDLY TRANSITS THE BLOOD-BRAIN BARRIER

GM6 binds rapidly and remains bound in vivo after 4 hours.

  • GM6 has a good brain-to-plasma ratio (1.65) in biomimetics measurement.

  • GM6 rapidly transits the blood-brain barrier enabling neuron survival through developmental-stage pathways: reducing inflammation, decreasing oxidative stress, reducing plaque formation, increasing growth factor, and decreasing apoptosis in the central and peripheral nervous systems.

GM6 BBB.png
 

GM6 Efficacy in Neuroprotection

GM6 DEMONSTRATES EFFICACY IN NEUROPROTECTION FROM TOXIC CSF IN MANY CNS DISEASES IN PRECLINICAL MODELS OF NEURODEGENERATION

Neurons die when exposed to toxicity from postmortem CNS patient’s Cerebrospinal Fluid (“CSF”)

GM6 demonstrated a statistically significant increase in neuron survival (p <0.0001) in:

  • ALS (175%)

  • MS (246%)

  • AD (191%)

  • HD (273%)

  • PD (198%)

  • Stroke (205%)

GM6 neuroprotection 2.png

Drug Properties

GM6 exhibits good drug-like properties

Estimated brain-to-blood ratio (log k BB) and the stead-state volume of distribution (log Vdss) of marketed drugs that enter into the CNS:

Drug Properties.png
 

The physicochemical properties of GM6 were measured using biomimetic HPLC membrane and protein binding.

GM6 exhibits good drug-like properties and is predicted to have good brain to  plasma ratio (Valko ADMET & DMPK 6(2) (2018) 71-73, 176-189).

GM6 has been predicted to have very strong tissue partition (log Vdss 0.89) and has a good brain-to-plasma ratio (1.65, lock BB 0.22).

As shown in the chart above, GM6 is well-positioned in the middle of the marketed drugs that enter in to the CNS based on the plot of the estimated brain-to-blood ratio (logk BB) and steady-state volume of distribution (log Vdss).

pipeline chart - large.png

 Pipeline