Genervon Biopharmaceuticals

Why Is Genervon Treating Individual ALS Patients after Phase 2A? Genervon's randomized, placebo-controlled Phase 2A clinical trial produced statistically significant efficacy results. Unfortunately, due to clinical trial rules, all participating patients are cut off from further access to the trial drug GM604 upon completion of the trial. In addition, Genervon was not allowed to know or follow up with any of the participating patients from these trials. We contracted Dr. Mit...sumoto of Columbia to collect patient data for our Phase 2A trial. The study and analysis of the data was performed by independent CROs and not by Dr. Mitsumoto. He offered one of our trial patients, whom we had never met, to be featured on a TV documentary about ALS by Asahi TV in Japan. The patient was originally given a life expectancy of only 2-3 years. However, over 2 years later, he stated on tv that he was no longer deteriorating, and all could see him talk and walk down the stairs in the documentary. The patient’s analyzed data also showed that he responded positively to his 6 doses of GM604. Until he was put on television, he was presented to Genervon only as a statistic. Wanting to observe and follow the progress of GM604 treated patients, we went overseas to treat a very broad base of PALS and are tracking their progress with their doctors very carefully to iterate on GM604 treatment protocols and to confirm the safety and efficacy of GM604 to our own satisfaction. We did not treat these patients for the FDA but will show the FDA the results.

Muti-target Peptide Drugs Endogenous embryonic stage master regulator drugs Visit http://www.genervon.com/ for more info.

ALS MOA Presentation Regulate over 30 ALS genes through 8 pathways Visit http://www.genervon.com/ for more info.

Clinical Pipeline There are 12 Phase 2 ready clinical trials in the pipeline. Visit http://www.genervon.com/ for more info.

Medicines Genervon has discovered and developed new classes of novel master regulators bio-drugs. These proprietary new classes of bio-drugs are high level fetal stage endogenous master regulators that modulate multiple pathways of gene expressions that are useful to treat disorders and diseases in nervous system and vascular system. Beyond these indications, Genervon is actively evaluating other diseases and indications such as cardiovascular, oncology, hematology and others... which are still proprietary and not in the public domain. Genervon is dedicated to the development of innovative therapeutics for patients with serious medical conditions involving the nervous system through the inhibition of processes leading to neuronal damage such as apoptosis, inflammation and oxidants. The company is currently conducting three Phase 2 trials evaluating its lead therapeutic for 1.) acute ischemic stroke patients under IND #77789, 2.) Parkinson's disease has been granted under IND #10944 and 3.) ALS was granted under IND #118420. See http://www.genervon.com/genervon/medicines.php

Therapeutic Applications ***ALS*** Genervon's scientists confirmed the mechanism of action (MOA) of ALS. GM604 controls over 4,000 genes, and modifies ALS disease progression by modulating 8 or more pathways involving up to 22 biologic functions concurrently and dynamically: 1. Insulin Receptor binding for ALS therapeutic effects. ... 2. Free Radical damages reduction for inhibition of ALS apoptosis. 3. PIP3 Kinase Activation for neuroprotection against ALS. 4. Bax inhibition reduced neuron death caused by ALS. 5. Akt activation to suppress SOD1 expression which caused ALS disorder. 6. Hypoxic response normalization to prevent ALS degeneration. 7. DNA repair capability increase against ALS neuron apoptosis. 8. Axonal transport stimulation to delay ALS onset GM604 also proved to be quite effective in the disease modification of ALS in ALS animals with mutant SOD1. It led to an improved clinical score in SOD1 mice (p<0.001 for all groups compared to control). Moreover, GM604 delayed the onset of ALS symptoms by 27%, extended life by 30% and delayed the median clinical score deterioration time in ALS mice by 41%. GM604 also provided neuroprotection against soluble inflammatory factors from ALS human patients' Cerebral Spinal Fluid (CSF) in vitro by 175%. GM604 dramatically increased the survival life span by 500% (6 fold from 7-14 weeks to 55-65 weeks) and increased of preservation of motor neurons by 160% (2.6 fold) in a Wobbler Mice Model for motoneuron diseases such as ALS. The design of optimal therapeutics by discovery of endogenous embryonic stage human master regulators is changing from hitting single pathways to a more comprehensive and dynamic approach addressing the complexity of neuro-degenerative disease. Genervon has a family of highly specific drug candidates that addresses this complexity, and believes it is at the forefront of a shift that is only beginning to be appreciated. Read more about other applications: http://www.genervon.com/genervon/science_development.php

Drug Discovery ***About GM6*** For drug development purposes, a drug target smaller than 33 amino acids is desirable. Within the original MNTF 33mer sequence, Genervon further identified nine active sites and multiple drug targets. In vitro and in vivo experiments have confirmed that all identified targets have statistically similar biological effects with variations as the 33mer. Genervon discovered MNTF, a novel patented family of 9 human master regulators of the nervous sy...stem highly expressed during week 9 of embryonic development. These Master Regulators are potent disease modification drug candidates modulating many pathways including inflammation, apoptotic, hypoxia etc. GM600, one of the master regulators is the chosen drug candidate because its size was proven to be able to penetrate the crucial blood-brain barrier. GM6 has all the advantages of a peptide-based drug: very high potency and activity, low toxicity, minimum drug-to-drug interaction, low accumulation in tissues (i.e., a short half-life), extremely high specificity, and little to no unspecific binding to molecular structures other than the desired targets. GM6 is small enough that it does not have the disadvantages of large peptides in terms of stability, solubility, mutagenicity, immunogenicity, or the high cost of manufacturing through transgenic or recombinant methods. More about Drug Discovery: http://www.genervon.com/genervon/science_discovery.php