GM604 Phase 2A Randomized Double-blind Placebo Controlled Pilot Trial in Amyotrophic Lateral Disease (ALS)

Background

1. In the early 1990s Genervon hypothesized that CNS/PNS and rare motoneuron diseases and
disorders involve the interplay of a highly complex, multifactorial process of many
non-dominant effectors in an interactive dynamic network. Therefore Genervon decided
for its drug development strategy the classic single target drug development paradigm
is not likely leading to a cure.

2. Genervon also hypothesized that aging is likely the initial multifactorial triggers
that lead to multiple defective or degraded gene products accumulating with advancing
years. However the key to a cure for many human neurological disorders is in the
subsequent common terminal cascade coinciding with the onset of neurological deficits.
The terminal cascade involves the shared pathways of interactive multifactorial
pathogenic mechanisms that lead to the ultimate demise of neurons. Therefore Genervon's
strategy is not to find the triggers or the residue debris of neuron death in discrete
areas of the central nervous system.

3. Genervon recognized the limited human capacity to design a drug that can dynamically
and interactively modulate multiple pathways and genes. Therefore one possible drug
development strategy is to find the endogenous early stage regulatory molecule(s) that
controls the development, monitoring and correction of the human nervous system.

4. Genervon developed a novel proprietary technology platform named Protein Bands
Selection by Function to find the fetal signal regulators. One of the discoveries is a
33 amino acid peptide we named human Motoneuronotrophic Factor (MNTF), its gene
sequence and its chromosome location.

5. Genervon developed another novel platform named In Silico Analysis to find active sites
within bigger proteins. Within the MNTF peptide, Genervon identified a family of nine
embryonic stage human multifactorial master regulators which govern nervous system
development, protection and correction. These master regulators are highly expressed in
week 9 of embryonic/fetal development, a time of incredible intricacies, but truly
remarkable consistency as well.

6. Genervon has developed one of the nine master regulators named GM6 for disease
modification of CNS/PNS and neurodegenerative diseases and disorders with shared or
common pathways of interactive multifactorial pathogenic mechanisms. GM6 binds to
Insulin Receptor beta sub-unit and IGF1R/IGF2R which also have the identical sub-unit.
GM6 penetrates the Blood Brain Barrier (BBB) and activates many appropriate genes
through multiple pathways to induce anti-inflammatory, anti-apoptotic, anti-oxidative
and regenerative effects in response to the dynamic distress signals from the nervous
system.

7. GM6 is also known as GM604, GM602 and GM608. Drug name GM604 is assigned to ALS
indication. GM602 is assigned to stroke indication. GM608 is assigned to Parkinson
Disease indication.

8. The investigational drug GM604 is a regulatory/signaling peptide with a sequence
identical to one of the nine active sites of human Motoneuronotrophic factor (MNTF),
also referred to as GM6 in studies. MNTF is a novel human endogenous developmental
stage neurotrophin for the nervous system with a specific human chromosome location.

9. Pre-clinical efficacy studies: The investigators' preclinical animal study has shown
that intravenously injected GM604 is able to penetrate the blood-brain barrier and
enter the brain. GM604 has shown neuroprotection in a variety of in vitro and animal
models of numerous CNS diseases including ALS, ischemic stroke, spinal cord injuries,
Parkinson's disease (PD), MS, Alzheimer and Huntington Disease.

10. GM6 provided neuroprotection for neurons in vitro against soluble inflammatory factors
in human CSF from patients with various CNS diseases. It increased neurons survival by
175% after exposure to ALS patients' CSF, by 191% in AD patients' CSF, by 198% in PD
patients' CSF, by 205% in Stroke patients' CSF, by 246% in MS patients' CSF and by 273%
in HD patients' CSF.

11. Preclinical research in animal models indicates GM604 to be a neuroprotective agent in
animal models of ALS, motoneuron disease, Parkinson's disease and stroke. In ALS model,
SOD1 mice from Jackson Lab stock #G93A were treated with GM604 at 0, 1 and 5 mg/kg.
SOD1 mice were examined for age of disease onset, age of death, and behavioral
expression of the disease (CS=Clinical score). GM604 prolonged life span in ALS mice
SOD1 by 30% [(163.5-126)/126 = 30%], delayed median clinical score by 53%, delayed
symptoms onset by 27% [(145.5-114.5)/114.5 = 27%] at 5 mg/kg dose. The conclusion is
that GM6 significantly showed a dose dependent effect in delaying age of onset of the
disease, age of death, increasing grip strength and rota-rod performance, and improving
clinical score of the treated animals.

12. The investigators found out later in the study of Wobbler Mouse model that the optimal
dose for SOD1 mice model should probably be 20 mg/kg and will probably see even more
significant effects if 20 mg/kg were used in the SOD1 mice study.

13. GM604 20mg/kg dramatically increased the survival life span by 500% (6 fold from 7-14
weeks to 55-65 weeks) and the control animals and animals treated with low doses of GM6
showed a continual decrease in grip strength. Wobbler mice treated with GM6 at 10-20
mg/kg showed an improvement in grip strength out to 4 weeks (3 fold). GM604 10 and 20
mg/kg treatment showed a significant increase in body weight out to 8 weeks following
treatment.GM604 10 and 20 mg/kg treatment increased of preservation of motor neurons by
160% (2.6 fold).

The conclusion is that GM604 was found to be efficacious in an in vivo mouse model of
neurological disease. The effectiveness of GM604 was dose-dependent and indicates that GM604
may be beneficial in treating various neurological disorders.

Rationales

1. This pilot trial is designed to test proof of principle, i.e. determine if a 2-week IV
bolus treatment with this agent can (1) change ALS protein expression (target
biomarkers and efficacy biomarkers) after treatment (2) have preliminary effects
measures of ALS disease clinical progression.

2. Previous human experience: A Phase 1 Clinical Trial Study has been completed. The Phase
1 Trial primary objective is to determine the safety and tolerability and to establish
the pharmacokinetic and pharmacodynamic properties of GM602 at 0.5, 1.5, and 5.0 mg/kg
administered as a single bolus intravenous dose in human subjects and after 3
consecutive daily doses of GM602 at the highest safe and tolerated dose of 5.0 mg/kg.
The Phase 1 study established that 3 consecutive daily doses of 5.0 mg/kg of GM602 are
safe and tolerated.

3. Concurrently, other IND and on-going clinical trials with GM6 are:

IND 77,789: "A Phase 2 double blinded, randomized, placebo controlled dose escalation Study
to Evaluate the Efficacy and the Safety of GM602 in Patients with Acute Middle Cerebral
Artery Ischemic Stroke within an 18 h-hour treatment window. Acronym/Title is GMAIS. GM602
received fast track designation for ischemic stroke in 2007. The stroke trial has not
completed enrollment and has not unblinded the treatment randomization to generate drug
related safety report.

IND 109,441: "GM602 in A Phase IIA Pilot double-blinded, randomized, placebo controlled
trial in mild to moderate Parkinson Disease (PD). Acronym/Title is GAP-PD. The PD trial is
recruiting patients.

Possible GM604 MOA in ALS

1. More and more scientists are publishing papers advocating that ALS is a multifactorial
disease. Other rare diseases including CNS/PNS diseases and disorders are
multifactorial and multisystem diseases as well, i.e. multiple interactive biologic
systems and genes are compromised and failing like domino.

2. One of the major reasons for CNS clinical trials that have uniformly failed is that the
classic drug development paradigm of designing single target drug for CNS/PNS and rare
diseases' pathogenesis simply would not be able to handle the multifactorial nature of
the complex diseases.

3. An initial trigger(s) which is likely to be multifactorial and cumulative is followed
by a terminal cascade which also involves interactive multifactorial pathogenic
mechanisms, coinciding with the onset of neurological deficits, genes mutation and or
expression of misfolded proteins. That is simply why a single target drug is not able
to do the job. Most neurological diseases and disorders have common underlying
pathogenic mechanisms that lead to neural death. Our drug development strategy is to
find an endogenous regulator to interactively and dynamically modulate these common
underlying pathogenic mechanisms.

4. Genervon changed the drug development paradigm from hitting a single gene/pathway to a
comprehensive and dynamic, multifactorial approach to treat complex rare and
neurodegenerative diseases with a multi-factorial drug GM604. GM604 is one of the
embryonic/fetal stage MNTF master regulators that is an endogenous signaling peptide
for the development and regulations of the nervous system development. GM604 is
multifactorial and corrects inadvertent errors in embryonic/fetal development and this
neuroprotection and correction property may be applied to neurodegenerative disease
therapy in adults.

5. Genervon studied the mechanisms of action of GM6 by DNA microarray technique. GM604
controls and modulates many known and significant ALS genes with positive effects,
through multiple pathways interactively, systemically and dynamically. Our master
regulator peptide drug modulates not just one but many ALS related genes. It is not a
cocktail of drugs, but one master regulator peptide drug.

6. Mechanisms that have been postulated in ALS are a complex interplay between multiple
pathogenic processes including oxidative stress, protein aggregation, mitochondrial
dysfunction excitotoxicity, and impaired axonal transport. GM604 modulates genes
involved in these pathways and others. Genervon has also identified some genes to be
tested as targets.

7. ALS is notoriously fatal and has many alternate forms with different pathogenesis.
Therefore all the previous single target drug trials have to restrict the enrollment to
very small selective segment of ALS patients. With the potential that GM604 functions
through multiple pathways and modulate multiple ALS related genes, Genervon believes
GM604 can potentially treat ALS patients from a variety of segments instead of
restricting to small selective segment of ALS patients. Genervon is proposing an ALS
Phase 2 clinical trial that is broadly inclusive.

Use of Biomarkers for ALS

Most late-phase clinical trials across all diseases fail to demonstrate drug efficacy
between case and controls. The incorporation of biomarkers within clinical trials may reduce
this 'drug attrition' rate. The biomarkers to be incorporated into clinical trials can be
subdivided into:

1. 'Target' biomarkers (the drug hits its target and, therefore, provide benefit),

2. 'Efficacy' biomarkers (indicators of positive drug effect (result) via the mechanism of
drug action).

3. 'Efficacy/Target biomarkers.

Genervon hypothesized that modulating disease causing genes may modulate ALS disease
progression.

Inclusion Criteria:

1. Patients with ALS: Familial and Sporadic ALS, with symptom onset < or equal to 24
months.

2. At least 18 years of age

3. Subjects meet the El Escorial criteria of definite criteria for a diagnosis of ALS.

4. Subjects can be on a stable dose of riluzole for at least a month or not taking or
initiating riluzole for the duration of the trial.

5. Not on any experimental medication for the last 1 month or five times the half-life
of experimental medication.

6. At screening, must have a Forced Vital Capacity (FVC) ≥ 65% of predicted capacity for
age, height and gender.

7. Have fully completed informed consent form

8. Ability to comply with study procedures

9. Women of child-bearing age must be on birth control. Pregnancy test should be done in
women in child bearing age.

10. Medically safe to have lumbar puncture to collect CSF

Exclusion Criteria:

1. History of liver disease, severe renal failure, diabetes, coronary heart disease,
cancer

2. Clinically significant EKG abnormality at screening

3. Any comorbid condition which would make completion of the trial unlikely

4. FVC < 65%

5. Presence of a bleeding disorder

6. Allergy to local anesthetics

7. Problem with CSF pressure

8. Topical or other skin infection at the lumbar puncture site

9. BMI > 32 kg/m2

10. Medical or surgical conditions in which a lumbar puncture is contraindicated

11. Use of any anti-platelet or anticoagulant drugs, such as plavix, aggrenox, ticlid,
warfarin or coumadin