Fovista (pegpleranib) / Roche, Astellas - LARVOL DELTA

A 24 Month Phase 2a Open Label, Randomized Study of Avastin®, Lucentis®, or Eylea® (Anti-VEGF Therapy) Administered in Combination With Fovista® (Anti-PDGF BB Pegylated Aptamer) (clinicaltrials.gov) - P2 | N=63 | Terminated | Sponsor: Ophthotech Corporation | Phase classification: P2a ➔ P2

Combination therapy • Phase classification • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Phase 2A Open Label Safety Study of Fovista® (Anti-PDGF BB) Regimen Administered in Combination With Anti-VEGF Therapy to Study Sub-Retinal Fibrosis in Neovascular AMD (clinicaltrials.gov) - P2 | N=101 | Terminated | Sponsor: Ophthotech Corporation | Phase classification: P2a ➔ P2

Combination therapy • Phase classification • Age-related Macular Degeneration • Fibrosis • Immunology • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Discovery of Aptamers and the Acceleration of the Development of Targeting Research in Ophthalmology. (PubMed, Int J Nanomedicine) - "Aptamers, including E10030, RBM-007, AS1411, and avacincaptad pegol, targeting other angiogenesis-related biomarkers have also been discovered and subjected to clinical trials. Aptamers used for early detection and treatment of ocular tumors were derived from other disease biomarkers, such as CD71, nucleolin, and high mobility group A. In this review, the development and application of aptamers in eye disorders in recent years are systematically discussed, which may inspire a new link between aptamers and eye disorders. The aptamer development trajectory also facilitates the discovery of the pathogenesis and therapeutic strategies for various eye disorders."

Journal • Review • Age-related Macular Degeneration • Diabetic Retinopathy • Eye Cancer • Fibrosis • Glaucoma • Immunology • Macular Degeneration • Ocular Melanoma • Oncology • Ophthalmology • Retinal Disorders • CTGF • NCL • TFRC • TGFB1

"Fovista? - what’s in a name? https://t.co/Z6u7RTUfEy" (@TonyFauci2)

Intravitreous treatment of severe ocular von Hippel-Lindau disease using a combination of the VEGF inhibitor, ranibizumab, and PDGF inhibitor, E10030: Results from a phase 1/2 clinical trial. (PubMed, Clin Exp Ophthalmol) - "Combination intravitreous injection with ranibizumab and E10030 demonstrated a reasonable preliminary safety profile, but limited treatment effect."

Clinical • Journal • P1/2 data • Glaucoma • Oncology • Von Hippel-Lindau Syndrome

"@ooredoo @Infovista @GileadSciences @Omantel @Huawei @USEKOfficial" (@Tahseenconsult)

A Phase 3 Safety and Efficacy Study of Fovista® (E10030) Intravitreous Administration in Combination With Either Avastin® or Eylea® Compared to Avastin® or Eylea® Monotherapy (clinicaltrials.gov) - P3; N=645; Terminated; Sponsor: Ophthotech Corporation; Active, not recruiting ➔ Terminated

Trial termination • Age-related Macular Degeneration • Biosimilar • Complement-mediated Rare Disorders • Gene Therapies

Ophthotech cuts to hit around 80% of staffers after phase 3 failures (FierceBiotech) - "...Ophthotech is to make swingeing cuts to its staff as it reels from two pivotal late-stage failures for its experimental eye drug Fovista...when used with Novartis’ marketed eye med Lucentis...There is another phase 3 test, expected to report mid-2017, that sees Fovista and Eylea with Roche's VEGF cancer med Avastin...used together in a combo trial."

Anticipated P3 data • Commercial • Age-related Macular Degeneration • Ophthalmology

Identification of Interacting Motifs Between Armadillo Repeat Containing 1 (ARC1) and Exocyst 70 A1 (Exo70A1) Proteins in Brassica oleracea. (PubMed) - Protein J - "This supports a model in which the N-terminal leucine zipper of ARC1 and the first 85 N-terminal amino acids of Exo70A1 mediate the interaction between these two proteins. Bioinformatic and phylogenetic analysis demonstrated that these motifs were highly conserved across different species, indicating that the interaction characterized in B. oleracea may operate in a wide array of cultivars."

Journal • Biosimilar

Phase 2A Open Label Safety Study of Fovista® (Anti-PDGF BB) Regimen Administered in Combination With Anti-VEGF Therapy to Study Sub-Retinal Fibrosis in Neovascular AMD (clinicaltrials.gov) - P2a; N=101; Terminated; Sponsor: Ophthotech Corporation; Trial primary completion date: May 2017 ➔ Dec 2016

Trial primary completion date • Age-related Macular Degeneration • Biosimilar • Complement-mediated Rare Disorders • Fibrosis • Gene Therapies • Immunology • Ophthalmology • Rare Diseases

Novartis: Q4 & FY 2015 Results (Novartis) - Anticipated regulatory filing for neovascular AMD in 2017

Anticipated regulatory • Ophthalmology

Fovista: Anticipated expiry of patents in US, EU, Japan, and ROW related to co-formulations and other proprietary technologies in 2033 (IVERIC bio) - Annual Report 2016: Anticipated expiry of patents in US, EU, Japan, and ROW related to co-formulations, dosing regimens and other proprietary technologies in 2034; Anticipated expiry of patents in US and under PCT covering dosing regimens and methods for treating AMD and other proprietary technology in 2035; Anticipated expiry of composition of matter patents in EU, Japan and ROW in 2018

Anticipated patent expiry • Age-related Macular Degeneration • Ophthalmology

Ophthotech announces results from pivotal phase 3 trials of Fovista in wet age-related macular degeneration (Iveric bio Press Release) - "Ophthotech...announced that the pre-specified primary endpoint of mean change in visual acuity at 12 months was not achieved in its two pivotal Phase 3 clinical trials investigating the superiority of Fovista...in combination with Lucentis...compared to Lucentis® monotherapy for the treatment of wet age-related macular degeneration (AMD). The addition of Fovista® to a monthly Lucentis® regimen did not result in benefit as measured by the mean change in visual acuity at the 12 month time point."

P3 data • Age-related Macular Degeneration • Ophthalmology

Nektar Therapeutics' CEO Howard Robin on Q3 2016 results - Earnings call transcript (SeekingAlpha) - "...an upcoming Phase III data catalyst is Ophthotech's Fovista for wet AMD...are on track to deliver top-line data from their Phase III program by the end of the year...Fovista is positioned for a potential launch in the fourth quarter of 2017. The current market for therapeutic screening wet AMD is $6 billion."

Anticipated launch • Anticipated P3 data: top line • Commercial • Age-related Macular Degeneration • Ophthalmology

Ophthotech announces results from third phase 3 trial of Fovista in wet age-related macular degeneration (Businesswire) - P3, N=640; NCT01940887; Sponsor: Ophthotech Corporation; "...pre-specified primary endpoint of mean change in visual acuity at 12 months was not achieved in its Phase 3 clinical trial investigating the superiority of Fovista...combination with Eylea® (aflibercept) or Avastin...Eylea® or Avastin® monotherapy for the treatment of wet age-related macular degeneration (AMD). The addition of 1.5mg of Fovista® to an Eylea® or Avastin® regimen did not result in benefit as measured by the mean change in visual acuity at the 12-month time point."

P3 data • Age-related Macular Degeneration • Ophthalmology

Fovista: Anticipated expiry of patents in US, EU, Japan, and ROW covering the treatment of wet AMD in combination with anti-VEGF-A antibody in 2024 (IVERIC bio) - Annual Report 2016: Anticipated expiry of patents in US, EU, Japan, and ROW for the treatment for AMD in combination with Eylea in 2030; Anticipated expiry of patents related to co-formulations of Fovista and anti-VEGF-A antibody in US in 2025; Anticipated expiry of patents related to co-formulations of Fovista and anti-VEGF-A antibody in EU, Japan and ROW in 2024; Anticipated expiry of patents in US, EU, Japan, and ROW covering methods of treatment of AMD in combination with Macugen in 2024

Anticipated patent expiry • Age-related Macular Degeneration • Ophthalmology

OphthoTech Corp: Annual Report 2015 (IVERIC bio) - Anticipated expiry of patents in US and under the PCT covering dosing regimens, methods of treating AMD and other proprietary technology in 2035; Anticipated expiry of composition of matter patent in US in 2017; Anticipated expiry of composition of matter patent in EU, Japan, and ROW in 2018

Anticipated patent expiry • Age-related Macular Degeneration • Ophthalmology

Ophthotech: Investor Day (IVERIC bio) - “FOVISTA® (1.5MG ANTI-PDGF) COMBINATION THERAPY MET THE PRE-SPECIFIED PRIMARY ENDPOINT”; “MEAN CHANGE IN VA (BASELINE TO WEEK 24)”; “Visual Outcome – Standard Baseline Variable”; “IMPROVED VISUAL OUTCOME, VISUAL LOSS/POOR VISUAL OUTCOME”

P2b data • Ophthalmology

Ophthotech reports fourth quarter and full year 2016 financial and operating results (Businesswire) - "...approximately $100 million to $115 million is committed to implementing...the immediate termination and winding-down of the Phase 3 Fovista® in combination with Lucentis® clinical trials, the termination of the Fovista® Expansion Studies, cancelation fees related to manufacturing commitments, and obtaining initial top-line data in the second half of 2017 for the Phase 3 Fovista® in combination with Eylea® (aflibercept) or Avastin® (bevacizumab) clinical trial."

Commercial • Trial termination • Age-related Macular Degeneration • Ophthalmology

Novartis: Q3 2016 Results (Novartis) - Anticipated regulatory filing for neovascular AMD in 2017

Anticipated regulatory • Ophthalmology

Ophthotech: Investor Day (IVERIC bio) - “OPH1005 Study: Anti-Fibrosis Study”; “Visual Outcome Over Time”; “6 Patients Have Month 14 Values”

P2a data • Ophthalmology

Translational Regulation of Dnm1, an Epileptic Encephalopathy Gene, by CELF4 (AES 2019) - "Rationale CELF4 is a brain-specific member of the CELF RNA binding protein (RBP) family that has been demonstrated to bind a significant portion of the transcriptome with striking selectivity for the 3’UTR of neuronal and synapse-specific functional targets in the hippocampus (PLoS Genet 2012, 8(11): e1003067)...Conclustions Molecular work showing a dosage dependent decrease in DNM1 after loss of the RBP CELF4, combined with similar decrease in Dnm1-Mut2 mice with mutated CELF4 binding sites in the Dnm1 3’-UTR, offer compelling evidence that CELF4 normally regulates DNM1 translation. The additional observation that CELF4 protein abundance is itself decreased in Dnm1-Mut2 mutant brain further supports the hypothesis that CELF4 acts on and responds to a network of high-ranking targets to help coordinate neuronal activity."

A Phase I/II Trial for Intravitreous Treatment of Severe Ocular Von Hippel-Lindau Disease Using a Combination of the PDGF Antagonist E10030 and the VEGF Antagonist Ranibizumab (clinicaltrials.gov) - P1/2; N=3; Completed; Sponsor: National Eye Institute (NEI); Active, not recruiting ➔ Completed; Trial completion date: May 2020 ➔ Jul 2019; Trial primary completion date: May 2020 ➔ Jul 2019

Trial completion • Trial completion date • Trial primary completion date

Lactobacillus salitolerans sp. nov., a novel lactic acid bacterium isolated from spent mushroom substrates. (PubMed, Int J Syst Evol Microbiol) - "...The average nucleotide identities were 74.1 % between strain YK43 and L. acidipiscis DSM 15836 and 74.0 % between YK43 and L. pobuzihii E100301...is proposed. The type strain is YK43 (=JCM 31331 = DSM 103433)."

Journal