quercinitol (ELND-005) / OPKO Health - LARVOL DELTA

Brain metabolite changes in mild and moderate Alzheimer’s disease: Correlation with V-MRI and clinical measures of disease severity (CTAD 2011) - P2, N=353; The observed elevation of myo-inositol levels in moderate compared to mild AD extend the prior findings in MCI and early/mild stages of AD; The correlation of mI to both brain volume and cognition supports the relevance of myo-inositol as a metabolic marker of AD progression

P2 biomarker data • Alzheimer's Disease

Transition Therapeutics announces fiscal 2013 year end financial results (Transition therapeutics Press Release) - "In fiscal 2013, the company recognized $17,933,500 as revenue which represents the milestone payment of $10,815,200 (US$11,000,000) received from Elan upon their commencement of the next ELND005 clinical trial and..."

Commercial • Alzheimer's Disease

A 78-week phase 2 study of ELND005 (scyllo-inositol) in Alzheimer’s disease: Clinical outcomes by various MMSE definitions of mild disease (CTAD 2011) - P2, N=353; In the post-hoc exploratory analysis, the Mild subgroup defined by MMSE range of 22-26 showed potentially larger ELND005 effects than the 20-26 range; Despite the smaller sample in the 22-26 MMSE range, the cognitive NTB endpoint approached statistical significance; These analyses support the choice of a mild AD group defined by MMSE of 22-26 inclusive as a population with potential for benefit from ELND005

P2 data • Alzheimer's Disease

α-Synuclein Aggregation, Seeding and Inhibition by scyllo-Inositol. (PubMed) - Biochem Biophys Res Commun - "In addition, an established amyloid inhibitor, scyllo-inositol, was examined for potential inhibitory effects on α-synuclein aggregation. TEM analysis of protein:inhibitor assays demonstrated that scyllo-inositol inhibits the aggregation of α-synuclein, suggesting the therapeutic potential of the small molecule in PD."

Journal • Biosimilar • Gene Therapies • Parkinson's Disease

Safety and Efficacy Study of ELND005 as an Adjunctive Maintenance Treatment in Bipolar I Disorder (clinicaltrials.gov) - P2; N=309; Terminated; Sponsor: Transition Therapeutics Ireland Limited; N=400 -> 309 ; Active, not recruiting -> Terminated

Enrollment change • Trial termination • Biosimilar • Hematological Malignancies

Aβ uptake by non-plaque associated microglia (AAICAD 2012) - In mice oral administration of 1-deoxy-1-fluoro- scyllo -inositol, a scyllo- inositol analogue improved spatial memory impairments & associated amyloid pathology in a dose-dependent manner; Study identified scyllo- inositol induced Aβ-containing microglia throughout the cortex & hippocampus of TgCRND8 mice

Preclinical-animal • Alzheimer's Disease

Elan reports second quarter and first half 2013 financial results (Elan Press Release) - "As part of Elan’s 2009 transaction with Johnson & Johnson...Under the terms of this transaction, Johnson & Johnson provided an initial $500.0 Million funding to Janssen AI and Elan has a 49.9% shareholding in Janssen AI. Any additional funding in excess of the initial $500.0 Million funding commitment...required to be funded equally by Elan and Johnson & Johnson up to a maximum additional commitment of $400.0 Million in total."

Commercial • Alzheimer's Disease

KLK1 and ZG16B proteins and arginine-proline metabolism identified as novel targets to monitor atherosclerosis, acute coronary syndrome and recovery. (PubMed) - "Metabolomic analysis revealed arginine and proline metabolism, glutathione metabolism and degradation of ketone bodies as the three main pathways altered. In conclusion, two novel urinary panels of proteins and metabolites are here for the first time shown related to atherosclerosis, ACS and patient's recovery."

Journal • Acute Coronary Syndrome • Atherosclerosis • Biosimilar • Dyslipidemia • Immunology • Inflammation

The "Other" Inositols and Their Phosphates: Synthesis, Biology, and Medicine (with Recent Advances in myo-Inositol Chemistry). (PubMed) - Angew Chem Int Ed Engl - "Some "other" inositols are medically relevant, for example, scyllo-inositol (neurodegenerative diseases) and D-chiro-inositol (diabetes). It is timely to consider exploration of the roles and applications of the "other" isomers and their derivatives, likely by exploiting techniques now well developed for the myo series."

Journal • Review • Biosimilar • Diabetes

Introducing Virtual Oligomerization Inhibition to Identify Potent Inhibitors of Aβ Oligomerization. (PubMed, J Chem Theory Comput) - "Results from the VOI performance on six known inhibitors of Aβ aggregation (brazilin, curcumin, EGCG, ELND005, resveratrol and tacrine) are in excellent agreement with the results of expensive experiments. VOI not only improves the efficiency of the antagonist screening for Aβ oligomerization, but also reduces the cost to perform the task. Attractively, the principle of VOI can also be applied to inhibitor screening for the aggregation of other amyloid proteins/peptides."

Journal • Alzheimer's Disease • CNS Disorders • Tauopathies And Synucleinopathies

Cantillon: Royalty’s latest bid could prove a bitter pill to swallow for Elan (The Irish Times) - "Royalty Pharma tightened the squeeze on Elan yesterday with a second revised offer...Royalty had sought to amend the conditions of its offer to avoid the bid lapsing if either or both of the proposals to spend a further $200 Million buyback shares or the sale of ELND-005 were approved."

Commercial

Royalty gets injunction in challenge to takeover panel on Elan bid (The Irish Times) - "The interlocutory order restrains the Panel from directing Royalty to lapse its increased offer to acquire Elan or from treating the offer as having lapsed if either or both of two particular resolutions before shareholders – the spin-off of the ELND-005 drug programme and a $200 million share buyback – are passed, but two other resolutions – the $1 billion Theravance investment and the AOP Orphan acquisition – are rejected."

Commercial • Corporate lawsuit

Elan shares rise as investors vote against transactions (The Irish Times) - "Elan shares rose the first time in three days this morning, after a majority of investors voted against three of four proposals that stand in the way of Royalty Pharma’s $6.7 Billion bid...Elan gained as much as 2.8 per cent and was trading up 1.5 per cent to €9.43 at 9.04 am in Dublin. The four transactions under consideration are...the sale of an experimental drug called ELND005 for Alzheimer’s disease to Speranza..."

Commercial

A 4-Week Safety Study of Oral ELND005 in Young Adults With Down Syndrome Without Dementia (clinicaltrials.gov) - P2a; N=23; Completed; Sponsor: OPKO Health, Inc.; Phase classification: P2 ➔ P2a

Phase classification