Oral Pyridorin (pyridoxamine) / Kowa, NephroGenex - LARVOL DELTA

Repurposing pyridoxamine for therapeutic intervention of intravascular cell-cell interactions in mouse models of sickle cell disease. (PubMed, Haematologica) - "Studies using platelets and neutrophils from sickle cell disease mice and patients suggested that treatment with pyridoxamine reduced the activation state of platelets and neutrophils. These results suggest that pyridoxamine may be a novel therapeutic and a supplement to hydroxyurea to prevent and treat vaco-occlusion events in sickle cell disease."

Journal • Preclinical • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • ICAM1

NephroGenex reports third quarter 2014 financial results (Businesswire) - "Continue to initiate clinical site operations and enroll patients in our Phase 3 Pyridorin trial; Complete the Pyridorin TQT cardiac safety study analysis and issue the complete study report by the end of 2014; On target to complete the EMA regulatory scientific advice procedure for our Pyridorin Phase 3 clinical program in the first quarter of 2015; Continue our preclinical program with intravenous Pyridorin for acute kidney injury."

Anticipated clinical data • Anticipated enrollment status • Anticipated EU regulatory • Anticipated preclinical • Acute Kidney Injury • Diabetic Nephropathy • Renal Disease

RTP drug developer NephroGenex files for IPO (The News & Observer) - "According to its filing with the Securities and Exchange Commission, NephroGenex hopes to raise $46 million from the IPO with its stock pricing at between $12 and $14 per share. The company plans to use $30 million from the IPO to fund phase III studies of pyridorin and $1.5 million to start developing an intravenous version of pyridorin to treat acute kidney injury, which the company sees as a 'very significant market opportunity.' "

Financing • Stock price • Acute Kidney Injury • Renal Disease

NephroGenex announces that the European Medicines Agency supports the company’s study design for ongoing trial in diabetic nephropathy (Businesswire) - P3, N=600; PIONEER (NCT02156843); "NephroGenex...today announced that the Company has received positive Scientific Advice from the European Medicines Agency (EMA) regarding their Phase 3 program with Pyridorin® in diabetic nephropathy that has been accepted by the U.S. Food and Drug Administration under a Special Protocol Assessment. The EMA indicated that the current Phase 3 program could be adequate to support a Marketing Authorization Application for full market approval in Europe."

European regulatory • Diabetic Nephropathy • Renal Disease

NephroGenex, Inc. announces presentation at the American Society of Nephrology’s Kidney Week 2014 (Businesswire) - "NephroGenex...announced the presentation of the novel design of its Phase 3 Pyridorin PIONEER clinical program at the American Society of Nephrology (ASN) Kidney Week meeting held here November 11-16, 2014....'Our poster presentation at the ASN highlights the key outcomes from our Phase 2 studies with Pyridorin in diabetic nephropathy, and how they informed the design of our pivotal Phase 3 study launched earlier this year,' said Pierre Legault, Chief Executive Officer of NephroGenex."

Clinical protocol • Diabetic Nephropathy • Renal Disease

Aminofluorene-Mediated Biomimetic Domino Amination-Oxygenation of Aldehydes to Amides. (PubMed) - Org Lett - "9-Aminofluorene derivatives acted as pyridoxamine-5'-phosphate equivalents for efficient, chemoselective, and operationally simple amine-transfer oxygenation reaction. Unprecedented RNH transfer involving secondary amine to produce secondary amides was achieved. In the presence of (18)O2, (18)O-amide was formed with excellent (95%) isotopic purity."

Journal • Biosimilar

Synergistic effects of telmisartan and pyridoxamine on early renal damage in spontaneously hypertensive rats (Mol Med Rep) - Combined use of telmisartan & pyridoxamine is superior to the single use of either drug on renoprotection, which may result from the alleviation of oxidative stress & the reduction of NF-κBp65 & p-ERK1/2 activation

Preclinical-animal • Renal Disease

Interaction between vitamin B6 metabolism, nitrogen metabolism and autoimmunity. (PubMed) - Plant Signal Behav - "In addition, we found a strong up-regulation of genes related to plant defense. Here, we further show that pdx3 mutants display a temperature-sensitive phenotype that is typical of autoimmune mutants and is possibly connected to the impaired nitrogen metabolism."

Journal • Biosimilar • Immunology

Application of UPLC-MS/MS Method for Analyzing B-vitamins in Human Milk. (PubMed) - Biomed Environ Sci - "This method was successfully applied for simultaneous analysis of ten B-vitamins in human milk."

Journal • Biosimilar

NephroGenex announces date of conference call to discuss third quarter 2014 financial results (Businesswire) - "The Company (Nephrogenex) will host a conference call the following day, Thursday, November 13, 2014 at 8 a.m. Eastern, to...provide an update on its PIONEER program for diabetic nephropathy and milestones for the remainder of 2014."

Anticipated conference • Anticipated pipeline update • Diabetic Nephropathy • Renal Disease

The B6 -vitamer Pyridoxal is a Sensitizer of UVA-induced Genotoxic Stress in Human Primary Keratinocytes and Reconstructed Epidermis. (PubMed) - Photochem Photobiol - "Previously, we have demonstrated that 3-hydroxypyridine-derived chromophores including B6 -vitamers (pyridoxine, pyridoxamine, and pyridoxal) are endogenous photosensitizers that enhance UVA-induced photooxidative stress in human skin cells. In addition to activational phosphorylation indicative of genotoxic stress [p53 (Ser15) and γ-H2AX (Ser139)], comet analysis indicated the formation of Fpg-sensitive oxidative DNA lesions, observable only after combined exposure to pyridoxal and UVA. In human reconstructed epidermis, pyridoxal pre-incubation followed by UVA exposure caused genomic oxidative base damage, procaspase 3 cleavage, and TUNEL-positivity, consistent with UVA-driven photooxidative damage that may be relevant to human skin exposed to high concentrations of B6 -vitamers."

Journal • Biosimilar • Ophthalmology

PDX1 Gene Mutation with Permanent Neonatal Diabetes Mellitus with Annular Pancreas, Duodenal Atresia, Hypoplastic Gall Bladder and Exocrine Pancreatic Insufficiency. (PubMed, Indian Pediatr) - "...Observation: A novel homozygous mutation p.K163R (c.488A>G) in the PDX1 gene was found. Parents were heterozygous for the same. This case highlights the importance of establishing the genetic diagnosis in all cases of neonatal diabetes mellitus."

Journal • Biosimilar • Diabetes • Growth Hormone

Identification of novel thermostable taurine-pyruvate transaminase from Geobacillus thermodenitrificans for chiral amine synthesis. (PubMed) - Appl Microbiol Biotechnol - "In addition, TPTAgth showed a unique mechanism of sulfonate/α-carboxylate recognition contributed by Arg163 and Gln160. We also determined the protein sequence fingerprint of TPTAs in the 3N5M subfamily, which involved Arg163 and Gln160 and seven additional residues from 413 to 419 and lacked Phe/Tyr22, Phe85, and Arg409."

Journal • Biosimilar

NephroGenex announces date of conference call to discuss second quarter 2014 financial results (NephroGenex Press Release) - "NephroGenex...will report its second quarter 2014 financial results on Monday, August 11, 2014 after the U.S. financial markets close. The Company will host a conference call the following day, Tuesday, August 12, 2014 at 8 a.m., to review the second quarter 2014 financial results and provide an update on its PIONEER program for diabetic nephropathy and milestones for the remainder of 2014."

Anticipated pipeline update • Diabetic Nephropathy • Renal Disease

NephroGenex to present at Jefferies 2014 Global Healthcare Conference in New York City (Businesswire) - "In the presentation, Mr. Legault will review the Company’s Pyridorin program for the treatment of diabetic nephropathy, for which it received Fast Track Designation and a Special Protocol Assessment from the FDA. Diabetic nephropathy is a chronic, degenerative disease of the kidney affecting about 6 million patients in the U.S. for whom there are few therapeutic options. The Company is preparing to launch its Phase 3 trial with Pyridorin during the second quarter of 2014."

Anticipated new P3 trial • Anticipated review • Diabetic Nephropathy • Renal Disease

NephroGenex: Rodman & Renshaw Global Investment Conference (Nephrogenex) - "NephroGenex Phase 2 Safety Trials"; "Pyridorin was well tolerated, had a benign safety profile, and slowed the rate of SCr increase in patients on stable SOC at screening"; "There were no meaningful differences between groups in AEs"; "There were increases in diarrhea and consitpation with the higher Pyridorin 300 mg bid dose"; "Diarrhea: Placebo = 6%, 150 mg = 3%, 300 mg = 11%", Constipation: Placebo = 4%, 150 mg = 4%, 300 mg = 10%"; "There were no differences between groups in SAEs, mortality or ESRD"; "There were no differences between groups for laboratory parameters (hematology, chemistry, HbA1c)"; "There was no effect of Pyridorin on the QTc interval"; "Pyridorin has a benign safety profile with the possible exception of a small increase in diarrhea and constipation with the higher dose of 300 mg bid"

P2 data • Diabetic Nephropathy • Renal Disease

NephroGenex: Annual Report 2014 (Nephrogenex) - Anticipated expiry of patents licensed by KUMC related to decreased dialysis related amyloidosis or dialysis related increases in permeability of the peritoneal membrane in a dialysis patient by 2016; Anticipated expiry of patents licensed by KUMC for urinary stone disease by 2021; Anticipated expiry of patents licensed by the University of South Carolina for treatment of diabetes associated increases in hypercholesterolemia or hypertriglyceridemia in a diabetic mammal in US by 2016 and ex-US by 2019; Anticipated expiry of patents licensed by SCRF related to treatment or prevention of acute renal injury or acute renal failure by 2026; Anticipated expiry of patents licensed by Vanderbilt University related to amelioration of at least one symptom of kidney disorder associated with oxidative stress, carbonyl stress, or combinations thereof by 2026; Anticipated expiry of patents licensed by VU for IV formulation by 2026

Anticipated patent expiry • Renal Disease

Nephrogenex: Jefferies Global Healthcare Conference (Nephrogenex) - "NephroGenex Phase 2b PYR-210"; "Established SOC patients approved by FDA for phase 3"; "Patients on established (or stable) standard of care (SOC) at screening exhibit a highly significant dose-dependent treatment effect in the FDA approvable RENAL patient population"; "Patient not on SOC at screening exhibited higher initial blood pressures, more frequent medication changes, and drops in blood pressure during treatment, confounding SCr measurements (overall study did not meet end point)"; "Pyridorin was well tolerated, had a benign safety profile (see Appendix), and slowed the rate of SCr increase in patients on stable SOC at screening" 

P2 data • Diabetic Nephropathy • Renal Disease

Nephrogenex: Rodman & Renshaw  Global Investment Conference (Nephrogenex) - Anticipated method of use (patient population and dosage) patent expiry in US in Dec 2028; Anticipated manufacturing patent expiry in US in Feb 2025; Anticipated patent term extension in EU until Jun 2029

Anticipated patent expiry • Renal Disease

NephroGenex: Corporate Presentation (Nephrogenex) - Anticipated patent expiry for method of use (including patient population and dosage) in EU in June 2029; Anticipated patent term extension in EU for method of use (including patient population and dosage) until 2034; Anticipated patent expiry for method of use (including patient population and dosage) in Canada in June 2024

Anticipated patent expiry • Renal Disease

NephroGenex: Company Presentation (Nephrogenex) - "Clinical Results"; "PYR-206"; "Mild to Moderate Diabetic Nephropathy – Dose 50 mg BID"; "Pyridorin at a 50 mg bid dose is well tolerated and slows the rate of SCr increase in mild to moderate disease patients"

P2 data • Diabetic Nephropathy • Renal Disease

PIONEER: Pyridorin in Diabetic Nephropathy (clinicaltrials.gov) - P3; N=328; Terminated; Sponsor: NephroGenex, Inc.; N=600 ➔ 328; Recruiting ➔ Terminated

Enrollment change • Trial termination • Biosimilar • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Renal Disease

Nephrogenex: Conference Call (Nephrogenex) - Anticipated review of 300 patients in P3 PIONEER trial for diabetic nephropathy in Q1 2016; Anticipated initiation of a second P3 trial for diabetic nephropathy in Q4 2015

Anticipated DSMB • Anticipated new P3 trial • Diabetic Nephropathy • Renal Disease

Nephrogenex: Annual Report 2013 (Nephrogenex) - Anticipated expiry of method of use patents licensed from Kansas University Medical Center in US, Europe and Japan for diabetic nephropathy in 2016; Anticipated expiry of method for manufacture in US in 2025; Anticipated expiry of patent in US for kidney disorders in 2032; Anticipated expiry of patent for use of treatment for nephropathy in US and EU in 2027

Anticipated patent expiry • Renal Disease

Pyridorin in Diabetic Nephropathy (clinicaltrials.gov) - P3; N=600; Not yet recruiting; Sponsor: NephroGenex, Inc.

New P3 trial • Phase shift • Biosimilar • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Renal Cell Carcinoma • Renal Disease