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  1. Seminar at MSBoston 2014:  Phase 2 results of the RADIANCE trial...
  2. MS Drug Discovered at TSRI Is Safe and Effective in Phase II Study   
  3. Scripps Research Institute Scientists Identify First Potentially Effective Therapy for Human Prion Disease   
  4. Probe from SRIMSC Enters Phase II/III Clinical trials.   
  5. The Scripps Molecular Screening Center becomes the first to have 1000 AIDs in PubChem!   
  6. Receptos Scientists Publish Determination of a High Resolution S1P1 Structure in Science   
  7. NIH Common Fund researchers uncover structure of important target for drug design   
  8. NIH Research Matters: Designing New Diabetes Drugs   
  9. Discovery of a treatable mechanism for avoiding the deadly response to flu: North County Times, Eurekalert [1, 2]    
  10. Nature: Suppression of TH17 differentiation and autoimmunity by a synthetic ROR ligand   
  11. Scripps Research and MIT scientists discover class of potent anti-cancer compounds    
  12. MLP Probe Project Leads to First in Human Studies    
  13. Business Wire:   Receptos Initiates Clinical Trials for S1P1 Agonist Program, Aimed at Multiple Sclerosis   
  14. Nature:   Quantitative reactivity profiling predicts functional cysteines in proteomes.

  15. Nature:   Anti-diabetic drugs inhibit obesity-linked phosphorylation of PPARc by Cdk5.
  16. Discovery and optimization of chemical probes to define important molecular signals in medicine.
  17. Nature Reviews Drug Discovery article:   Chemical modulators of S1P receptors as barrier-oriented therapeutic molecules.
  18. Nature Chemical Biology article: S1P1 signaling just keeps going and going and going…
  19. Nature Biotechnology article:   Identification of selective inhibitors of uncharacterized enzymes by high-throughput screening with fluorescent activity-based probes.


Phase 2 results of the RADIANCE trial: a randomized, double-blind, placebo-controlled trial of oral RPC1063 in elapsing multiple sclerosis

J Cohen1, DL Arnold2,3, G Comi4, A Bar-Or5, S Gujrathi6, JP Hartung6, A Olson6, M Cravets6, PA Frohna6, K Selmaj7
1Cleveland Clinic, Mellen Center for MS Treatment and Research, Cleveland, OH, United States, 2NeuroRx Research, Montreal, QC, Canada, 3McGill University, Montreal, QC, Canada, 4San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Neurology, Milan, Italy, 5Montreal Neurological Institute, Department of Neurology and  Neurosurgery, Montreal, QC, Canada, 6Receptos, Inc., Clinical Development, San Diego, CA, United States, 7Medical University of Lodz, Department of Neurology, Lodz, Poland
Background: RPC1063 is an oral, selective sphingosine 1-phosphate 1 receptor modulator in clinical development for the treatment of relapsing multiple sclerosis (RMS).
Objectives: Demonstrate the superior efficacy of low (LD, 0.5 mg) and high (HD, 1.0 mg) dose RPC1063 vs. placebo (PBO), and characterize the safety of RPC1063 in patients with RMS.
Methods: RADIANCE is an international, combined Phase 2/3 trial. In the 24-week, Phase 2 portion, 258 patients were randomized (1:1:1) to PBO (n=88), LD (n=87) or HD (n=83). The primary endpoint was the cumulative number of total gadolinium-enhancing (GdE) lesions on MRI at Wks 12, 16, 20 and 24. Key secondary endpoints included number of GdE lesions at Wk 24, cumulative number of new/enlarging T2 lesions from Wks 12-24, and annualized relapse rate (ARR). Safety was assessed using vital signs, labs, ECG, Holter monitoring, PFT, OCT and adverse events (AEs). Patients were titrated to their assigned dose over one week to mitigate first dose heart rate effects.
Results: 98% of patients completed the trial. Cumulative total Wk 12-24 GdE lesions was reduced 86% in both RPC1063 arms vs. PBO (mean ± SD: PBO 11.1 ± 29.9, LD 1.5 ± 3.7, HD 1.5 ± 3.4, both p< 0.0001). Numbers of GdE lesions at Wk 24 were significantly reduced 91 and 94% (PBO 3.2 ± 9.8, LD 0.3 ± 0.9, HD 0.2 ± 0.6, both p< 0.0001) and cumulative Wks 12-24 new/enlarging T2 lesions 84 and 91% (PBO 9.0 ± 20.9, LD 1.4 ± 3.2, HD 0.8 ± 1.9, both p< 0.0001). A favorable trend in ARR reduction was observed vs. PBO (LD: 31%, p=0.27; HD: 53%, p=0.053).
The AE profiles were comparable between groups. The most common AEs in combined RPC1063 vs. PBO were nasopharyngitis (9.4 vs 13.6%), headache (4.7 vs 9.1%), and urinary tract infection (4.7 vs 2.3%). During the first 6 hours post first dose of RPC1063, maximum reductions in mean hourly heart rate were < 2 bpm from baseline and no patient had a minimum hourly heart rate < 45 bpm. No notable cardiac, pulmonary, ophthalmologic or malignancy AEs were observed. Transient alanine aminotransferase ≥3x upper limit of normal occurred in 3 patients (LD 2 (2.3%), HD 1 (1.2%)) that decreased with continued treatment.
Conclusions: Both doses of RPC1063 demonstrated large, significant and consistent reductions of all MRI measures of MS disease activity. The tolerability and safety results suggest a favorable risk-benefit profile of RPC1063 in the treatment of RMS. These results support the ongoing Phase 3 portion of the RADIANCE trial of RPC1063 vs. interferon beta-1a in RMS (NCT02047734).
Assigned speakers:
MD Amit Bar-Or , McGill University , Montreal , CA
Assigned in sessions:
13.09.2014, 08:30-10:00, Late breaking news, LB1, Late Breaking News (LB1.1-LB1.7), Auditorium

MS Drug Discovered at TSRI is Safe and Effective in Phase II Study


A compound discovered and synthesized in The Scripps Research Institute (TSRI) labs of Professors Hugh Rosen and Edward Roberts has provided positive results for safety and efficacy in Phase 2 clinical trials for relapsing multiple sclerosis, according to Receptos, the biopharmaceutical company developing the drug for approval by the US Food and Drug Administration.

“The Rosen and Roberts laboratories are very gratified to see these direct improvements in the lives of patients and families dealing with this debilitating illness,” said Rosen. “These data support our labs' approach at TSRI—that discovery of fundamental mechanisms in chemical biology provides the foundation for intelligent intervention in disease processes. Meeting the needs of patients and their families is our high calling in biomedical science.”

The drug candidate, RPC1063, was first discovered at TSRI from work in the National Institutes of Health (NIH) Molecular Libraries Initiative. The randomized, double-blind Phase 2 study assessed the efficacy, safety and tolerability of two orally administered doses of RPC1063 against placebo in 258 patients with relapsing multiple sclerosis across 77 sites in 13 countries. There was a highly statistically significant 86 percent reduction in MRI measures of disease activity.

A Phase 3 trial—a randomized, double-blind study involving 1,200 patients with relapsing multiple sclerosis—was launched in December 2013.

The detailed clinical abstract can be found  here.

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