Aphios amylon ncs_presentation_110113


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Aphios amylon ncs_presentation_110113

  1. 1. Partnering for the future of human health™ a wholly owned subsidiary of Aphios Corporation Developing a Novel Therapeutic, APH-1104 for Alzheimer’s Disease and Cognitive Disorders Dr. Trevor P. Castor President & CEO 3-E Gill Street, Woburn, MA 01801, USA November, 2013
  2. 2. Partnering for the future of human health™ Alzheimer’s Disease (AD)  The average time from diagnosis to death is 4 to 8 years, although it may take 20 years or more for the disease to run its course  Significant neurological disorder that affects more than 4.5 million Americans and more than 10 million people worldwide  Total market of AD drugs in 2005 was over $2.7 billion; the market is expected to grow at a rate of 17.5% per year  The 4 FDA-approved drugs (e.g. Aricept, a cholinesterase inhibitor) only treat the symptoms, not the underlying disease; currently, there is no cure for AD
  3. 3. Partnering for the future of human health™ Amyloid Plaque and Neurofibrillary Tangle Formation in Alzheimer’s Disease
  4. 4. Partnering for the future of human health™ Novel Alzheimer’s Disease Therapeutics  Proteolytic processing of APP leading to extracellular A deposits involves the action of - and γ-secretases  Inhibitors of both - and γ-secretases have been evaluated as A plaque-suppressing therapeutics in AD; while they are active in vitro, clinical trials have been largely unsuccessful  A recent Phase III clinical trial with Semagacestat, a γ-secretase inhibitor, by Eli Lilly was halted because of accelerated dementia  A recent Phase II clinical trial with a β-secretase inhibitor, LY2886721, also by Eli Lilly, was halted because of liver toxicity  There have been several Phase II and III clinical trial failures by Pfizer, AstraZeneca, Johnson & Johnson and Baxter
  5. 5. Partnering for the future of human health™ APH-1104 for Alzheimer’s Disease • A potent α-secretase modulator for ameliorating Alzheimer's Disease pathophysiology and cognitive impairment with neuroprotection • Exploratory Phase I/IIa clinical trial in the Bahamas (IV administration) • Preclinical development of oral formulation (capsule and PNS nanotechnology) • Next Steps – IND followed by Phase I/II clinical trials in the US
  6. 6. Partnering for the future of human health™ APH-1104 - Novel AD Therapeutic  APH-1104, an analog of APH-0703, up-regulates the production of -secretase which cleaves the amyloid precursor protein APP into a harmless soluble form sAPP- , which is non-neurotoxic and limits the formation of amyloid plaques  Both β-secretase and γ-secretase cleave APP to form an insoluble amyloid plaque (A ) that leads to tau entanglement  Thus, unlike current strategies which suppress β-secretase and γsecretase to minimize A plaque formation, our strategy involves the activation of α-secretase leading to beneficial amyloid precursor processing and prevention of A buildup
  7. 7. Partnering for the future of human health™ Nanoencapsulated APH-0703 Effectively Activates -Secretase in Neuroblastoma Cells APH-0703 α–secretase activity induced by APH-0703, Nano A, Nano B, Nano C and Nano D at 10-8M, 10-9M , 10-10M in SH-SY5Y neuroblastoma cells for 3h
  8. 8. Partnering for the future of human health™ Morris Maze Trials A B Latency to escape (Seconds to reach hidden platform) Morris Maze trials (A) were conducted to measure the latency in seconds (B) of wild type and AD transgenic mice treated with vehicle alone and 5 g APH-0703 to escape from mice swimming pool
  9. 9. Partnering for the future of human health™ APH-0703
  10. 10. Partnering for the future of human health™ Phase I/IIa Exploratory Clinical Study of APH-0703, Nassau, Bahamas (n= 1) • Patient - a 95 year old male with severe Alzheimer’s Disease • Over 6-month period, MMSE score dropped from 20 to 15 • ADAS-Cog score increased from 29 to 38 • Patient also on several medications including Donepezil (Aricept 10 mg) and Memantine (10 mg) for memory loss • After 2 i.v. cycles of APH-0703, patient very alert, remembers date, mind active, engaged in watching TV, aware of need to relieve himself, sleeping through the night
  11. 11. Partnering for the future of human health™ Summary  APH-0703, intravenously administered, shows preliminary efficacy in an Alzheimer’s Disease patient (n=1 study)  APH-0703 is a potent activator of -secretase which cleaves APP to form the soluble s-APP which is harmless, supports the formation of synapses, and can be removed in neuronal fluids  Nanoencapsulated APH-0703 significantly increases that activity of native APH-0703 in -secretase and PKC in vitro assays  APH-0703 continues to stimulate -secretase for at least 24h after it is removed from the cellular environment
  12. 12. Partnering for the future of human health™ Summary (continued)  Oral APH-0703 in oil and nanoparticle formulations significantly improve learning and memory retention in the transgenic mouse model, APP/PS1, of Alzheimer’s disease  These effects are seen within 2 weeks of administration, earlier than in any previous study  Retention studies indicate that memory improvements persist for at least 3 weeks following drug washout  APH-1104, a more potent analog of APH-0703, formulations represent a highly effective modality for treating Alzheimer’s Disease
  13. 13. Partnering for the future of human health™ Next Steps  Establish cGMP for API and FDP at the pilot-scale level (ongoing)  Establish a Drug Master File, design IND enabling preclinical studies and Phase I/IIa clinical trials, and draft IND package (ongoing)  Conduct FDA-necessary IND-enabling preclinical in vivo studies, including toxicology, efficacy and pharmacology, under GLP  Perform stability testing of API and FDP under GLP  File IND for conducting Phase I/IIa clinical trial of oral APH-1104  Conduct Phase IIb clinical trials
  14. 14. Partnering for the future of human health™ Contact Information • Office Phone: 001 (781) 932-6933 • Cell Phone: 001 (781) 858-7520 • Office Fax: 001 (781) 932-6865 • E-mail: tcastor@aphios.com • Website: www.aphios.com • Mailing Address: 3-E Gill St. Woburn, Dr. Trevor P. Castor, MA 01801 USA CEO