Reata Has Clinical Trial Design for Phase 3 Polycystic Kidney Disease Treatment

Reata Pharmaceuticals, Inc. (Nasdaq: RETA), a clinical-stage biopharmaceutical company, today announced that it has completed a successful end-of-Phase 2 meeting with the United States Food and Drug Administration (FDA) regarding the design of a Phase 3 clinical trial of bardoxolone methyl (bardoxolone) in patients with autosomal dominant polycystic kidney disease (ADPKD).

The trial, named FALCON, will be an international, double-blind, placebo-controlled, parallel group, Phase 3 trial.  The Company plans to enroll approximately 300 ADPKD patients randomized 1:1 to oral, once-daily bardoxolone or placebo.  The trial will include ADPKD patients from 18 to 70 years old with an estimated glomerular filtration rate (eGFR) between 30 to 90 mL/min/1.73 m².  The primary efficacy endpoint is the change from baseline in eGFR compared to placebo after 48 weeks of treatment followed by a 4-week drug withdrawal period, the retained eGFR benefit.

FALCON is statistically powered to detect a placebo-corrected, retained eGFR benefit of 1.6 mL/min/1.73 m².  Based upon guidance from the FDA, the 52-week retained eGFR benefit data may support accelerated approval under subpart H.  After Week 52, patients will be restarted on study drug with their original treatment assignments and will continue on study for a second year.  The second-year retained eGFR benefit will be measured at Week 104 after withdrawal of drug for four weeks.  Based upon guidance from the FDA, the year-two retained eGFR benefit data may support full approval.

The Company expects to initiate enrollment in the FALCON trial during mid-2019.

https://www.marketscreener.com/REATA-PHARMACEUTICALS-INC-28377265/news/Reata-Announces-Clinical-Trial-Design-for-FALCON-a-Phase-3-Trial-of-Bardoxolone-Methyl-for-the-Trea-27820155/

Senseonics 1st Study Participant Implanted in Monitor Study

Senseonics Holdings, Inc. (NYSE-American: SENS), a medical technology company focused on the development and commercialization of a long-term, implantable continuous glucose monitoring (CGM) system for people with diabetes, today announced that the extended life Eversense® XL sensor that lasts up to 180 days has been implanted in the first U.S. study participant as part of the clinical trial for pre-market application submission to the Food and Drug Administration.

The PROMISE Clinical Study is intended to evaluate the safety and efficacy of the Eversense CGM system in people with diabetes over a 180-day period. Approximately 180 study participants at up to 15 locations across the United States are planned to enroll in the study. The Eversense XL sensor previously received the CE Mark and is currently marketed to patients across the European Union.

Senseonics also announced that the company has completed its submission of PMA supplements to the FDA to secure an insulin dosing claim and to remove the contraindication related to the Magnetic Resonance Imaging (MRI) exposure on the 90-day system which is currently available in the United States.

https://www.marketscreener.com/SENSEONICS-HOLDINGS-INC-26786073/news/Senseonics-Announces-First-Study-Participant-Implanted-in-the-U-S-as-Part-of-the-PROMISE-180-Day-27820424/

Bausch Health’s Bausch + Lomb Gets Canada OK for Glaucoma Treatment

Bausch + Lomb, part of Bausch Health (BHC), said Thursday that Health Canada issued a notice of compliance for Vyzulta for the treatment of glaucoma.

Vyzulta is indicated for the reduction of intraocular pressure in patients with open-angle glaucoma or ocular hypertension.

https://www.marketscreener.com/BAUSCH-HEALTH-COMPANIES-I-44965076/news/Bausch-Health-Lomb-Gets-Canadian-Approval-for-Glaucoma-Treatment-27818120/

Clinical Trial Launches to Develop Breath Test for Multiple Cancers

Owlstone Medical (or the “Company”), a global diagnostics company developing a breathalyzer for applications in early disease detection and precision medicine, and Cancer Research UK, today announces the clinical launch of the PAN Cancer trial for Early Detection of Cancer in Breath¹, with the first patients now being recruited for the 1,500 patient study.

As previously announced on initiation of the collaboration, researchers in the trial are using Owlstone Medical’s² Breath Biopsy^® platform to collect samples, including healthy individuals as trial controls, to analyze volatile organic compounds (VOCs) in the breath.  The trial aims to identify VOCs that can be used as breath-based biomarkers to detect and differentiate different cancer types, thereby improving early detection.

This approach holds great promise as cancer cells display altered metabolism even at the very earliest stage of disease, affecting the pattern of the VOCs exhaled. By identifying the changing pattern of VOCs early, Owlstone Medical’s Breath Biopsy technology could detect cancer at the earliest stage of disease, when treatments are more effective and more lives can be saved.

The trial is recruiting 1,500 patients at Addenbrooke’s Hospital in Cambridge who have been referred from their GP with these specific types of suspected cancer. Prior to other diagnostic tests, breath samples will be collected using Owlstone Medical’s ReCIVA^® Breath Sampler and processed in Owlstone Medical’s Breath Biopsy laboratory in Cambridge, UK.

The clinical trial has initiated in patients with suspected oesophageal and stomach cancers and will expand to prostate, kidney, bladder, liver and pancreatic cancers in the coming months. Research is anticipated to run through 2021, and if the technology proves to accurately identify cancer the team hope that breath biopsy could in the future be used routinely in GP practices to determine whether to refer patients for further diagnostic tests.

Professor Rebecca Fitzgerald, lead trial investigator at the Cancer Research UK Cambridge Centre, said: “We urgently need to develop new tools, like this breath test, which could help to detect and diagnose cancer earlier, giving patients the best chance of surviving their disease. Through this clinical trial we hope to find signatures in breath needed to detect cancers earlier – it’s the crucial next step in developing this technology. Owlstone Medical’s Breath Biopsy technology is the first to test across multiple cancer types, potentially paving the way for a universal breath test.”

Billy Boyle, co-founder and CEO at Owlstone Medical, said: “There is increasing potential for breath-based tests to aid diagnosis, sitting alongside blood and urine tests in an effort to help doctors detect and treat disease. The concept of providing a whole-body snapshot in a completely non-invasive way is very powerful and could reduce harm by sparing patients from more invasive tests that they don’t need.

“Our technology has proven to be extremely effective at detecting VOCs in the breath, and we are proud to be working with Cancer Research UK as we look to apply it towards the incredibly important area of detecting early-stage disease in a range of cancers in patients.”

Almost half of cancers are diagnosed at a late stage in England³. This highlights the importance of early detection, particularly for diseases like oesophageal cancer where only 12% of oesophageal cancer patients survive their disease for 10 years or more. For example, Rebecca Coldrick, 54 from Cambridge, was diagnosed in her early 30s with Barrett’s oesophagus, a condition where the cells lining the oesophagus are abnormal – often caused by acid reflux. Out of 100 people with Barrett’s oesophagus in the UK, up to 13 could go on to develop oesophageal adenocarcinoma⁴.

Rebecca Coldrick said: “About 20 years ago I developed acid reflux, and I began to live on Gaviscon and other indigestion remedies. I went to the doctors and shortly after I was diagnosed with Barrett’s. Every two years I have an endoscopy to monitor my condition.”

Dr David Crosby, head of early detection research at Cancer Research UK, said: “Technologies such as this breath test have the potential to revolutionize the way we detect and diagnose cancer in the future. Early detection research has faced an historic lack of funding and industry interest, and this work is a shining example of Cancer Research UK’s commitment to reverse that trend and drive vital progress in shifting cancer diagnosis towards earlier stages.”

Recognising the importance of early detection in improving cancer survival, Cancer Research UK has made research into this area one of its top priorities and will invest more than £20 million a year in early detection research by 2019.

To find out more about Owlstone Medical’s Breath Biopsy® platform, visit: https://www.owlstonemedical.com/science-technology/breath-biopsy/

https://www.biospace.com/article/clinical-trial-launches-to-develop-breath-test-for-multiple-cancers/

AstraZeneca Spinoff Viela Bio Reports Positive Phase IIb Trial in Rare Disease

Viela Bio, based in Gaithersburg, Md., announced that N-MOmentum, its Phase IIb pivotal trial of inebilizumab, met both primary and key secondary endpoints in neuromyelitis optica spectrum disorder (NMOSD).

Viela Bio was spun out of AstraZeneca’s MedImmune arm in February 2018 with six molecules from its early-stage inflammation and autoimmunity programs. Inebilizumab was the lead compound, which at the time was in Phase II development for neuromyelitis optica. The disease affects the optic nerve and spinal cord in about 5 in 1,00,000 people. The U.S. Food and Drug Administration (FDA) granted the drug Orphan Drug Designation in 2016 and the European Medicines Agency (EMA) gave it the same status in 2017.

Viela Bio launched with up to $250 million from a consortium of investors led by Boyu Capital, 6 Dimensions Capital, and Hillhouse Capital. AstraZeneca is the largest minority shareholder.

NMOSD is a recently proposed term used for neuromyelitis optica (NMO), which is also called Devic’s disease. It is a rare, severe, relapsing, neuroinflammatory autoimmune disease that can be fatal. About 80 percent of patients with NMOSD have autoantibodies to a water channel protein dubbed aquaporin-4 (AQP4). The AQP4-IgG autoantibodies bind primarily to astrocytes in the central nervous system, which can trigger attacks, leading to damage of the optic nerves, spinal cord and brain. This can lead to loss of vision, paralysis, loss of sensation, bladder and bowel dysfunction, nerve pain, and respiratory failure.

N-MOmentum enrolled 231 NMOSD patients, including patients with and without AGP4-IgG antibodies. They were randomized to receive two IV doses of inebilizumab monotherapy or placebo and followed for 6.5 months. They were then placed into an open-label extension where all patients received inebiluzumab for 6 months.

The primary endpoint of the trial was time from treatment initiation to occurrence of an NMOSD attack. Results showed a 77 percent decrease in the risk of developing NMOSD attack in patients receiving inebilizumab monotherapy compared to placebo. Secondary analysis showed a decrease in worsening of disability in patients receiving the drug.

Safety and tolerability were acceptable and consistent with previous data.

“These results support our hypothesis that CD19 expressing B cells including plasmablasts and plasma cells play a key role in the pathogenesis of NMOSD,” stated Jorn Drapa, Viela Bio’s chief medical officer and head of Research & Development. “This study demonstrated a highly significant and clinically meaningful reduction in attack risk and suggests a promising new treatment for patients diagnosed with NMOSD. We would like to thank the investigators, hospitals and most of all the patients who took part in this trial, without whom medical advancements would not be possible.”

Two of the company’s other portfolio drugs it brought from MedImmune include MEDI4920, now VIB4920, an anti-CD40L-Tn3 fusion protein to treat Sjögren’s syndrome, and MEDI7734, now VIB7734, to treat myositis. Sjögren’s syndrome is an immune system disorder noted for dry eyes and mouth that is often found along with other immune diseases, such as rheumatoid arthritis and lupus. Myositis is an inflammation of the muscles. Both are in Phase I trials. Three other programs are in preclinical or research stages.

https://www.biospace.com/article/astrazeneca-spinoff-viela-bio-reports-positive-phase-iib-trial-in-rare-disease/

Merck Licenses NASH Compound From NGM Biopharma for $20 Million

Merck & Company has licensed NGM313, now renamed MK-3655, from South San Francisco-based NGM Biopharmaceuticals. MK-3655 is a monoclonal antibody agonist of the b-Klotho/FGFR1c receptor complex. The drug is being studied to treat nonalcoholic steatohepatitis (NASH) and type 2 diabetes.

The option was triggered by NGM’s completion of a proof-of-concept study of the compound. Under the terms of the deal, Merck picks up exclusive worldwide rights to develop, manufacture and commercialize MK-3655 and related compounds.

Merck paid NGM $20 million up front. NGM holds an option at the launch of the first Phase III clinical trial of the compound, to participate in up to 50 percent of a global cost and revenue sharing deal for the drug. If NGM chooses not to exercise that option, it will be eligible for more payments associated with the progress of MK-3665 in addition to commercial milestones and tiered royalties.

“Merck’s decision to exercise its option for NGM313 provides a strong endorsement of NGM’s powerful drug discovery engine and our ability to translate our novel biologic insights in the clinic,” stated David Woodhouse, NGM’s chief executive officer. “The Phase Ib data we presented last year demonstrate NGM313’s potential as a potent, once-monthly insulin sensitizer for the treatment of both NASH and type 2 diabetes. We look forward to Merck’s advancement of this program through clinical development to potentially address the substantial unmet medical need for a single treatment that addresses pathophysiological states common to both diseases.”

NGM released positive data from its Phase Ib trial of NGM313 in November 2018. The company was evaluating it in obese, insulin resistant patients with nonalcoholic fatty liver disease (NAFLD). They showed that a single dose of the compound had a statistically significant decrease in liver fat content and improvements in several metabolic parameters after five weeks.

Merck expects to advance MK-3655 into a Phase IIb trial in NASH with or without diabetes.

NASH is a huge unmet medical need linked to the obesity epidemic. It resembles cirrhosis of the liver but affects people who are not necessarily heavy drinkers. There are no specific treatments except for lifestyle changes—exercise and losing weight.

NASH can cause liver scarring and inflammation that can lead to liver cirrhosis, as well as cardiac and lung problems, liver cancer and death.

The National Institutes of Health (NIH) estimate that as many as 30 million Americans, or 12 percent of U.S. adults, currently have NASH. Maria Yataco, a gastroenterologist at the Mayo Clinic in Jacksonville, Fla., who conducts NASH and liver disease research, told CNBC, “By 2020 NASH will overtake hepatitis C as the No. 1 cause of liver transplantation in the U.S.”

There are even people in their 20s and 30s showing signs of NASH, according to Leona Kim-Schluger, a hepatologist and professor at the Recanati/Miller Transplantation Institute at Mount Sinai Hospital in New York. “There is even NASH in the pediatric population,” she told CNBC.

The global market for a NASH treatment is projected to be about $35 billion. According to BioMedtracker, there are 55 NASH drugs in clinical trials, with only four in Phase III trials. Most, 33, are in Phase II.

Other companies focused on NASH include Gilead Sciences, Allergan, Intercept Pharmaceuticals, and French biotech company GENFIT. Intercept’s Ocaliva (obeticholic acid) has been approved by the U.S. Food and Drug Administration (FDA) to treat another liver disease, primary biliary cholangitis. It is currently in a Phase III trial for patients with advanced-stage NASH, with interim data expected in the first half of this year.

https://www.biospace.com/article/merck-licenses-nash-compound-from-ngm-biopharma-for-20-million-up-front/

Locus, Janssen In Potential $818M Deal to Develop CRISPR-Based Antibacterials

Locus Biosciences, based in Research Triangle Park, NC, inked a collaboration and license deal with Janssen Pharmaceutical, a Johnson & Johnson company. The companies will work to develop precision antibacterial therapies based on CRISPR-Cas3-enhanced bacteriophage.

Under the terms of the deal, Janssen is paying Locus $20 million up front. Locus will be eligible for up to a total of $798 million in development and commercial milestones, as well as royalties on any product sales.

Locus focuses on using Type 1 CRISPR-Cas3 to degrade the DNA of target bacteria, which quickly kills them. One advantage of this approach over antibiotics is it targets the specific bacteria without wiping out the desirable “good” bacteria in the body.

“Our collaboration with Janssen on the development of products to treat deadly infections and potentially other microbiome dysbiosis associated conditions reflects the importance of the crPhage platform and its potential to revolutionize the treatment of disease and extend human life,” stated Paul Garofolo, Locus’s chief executive officer. “Our platform is uniquely positioned to selectively eradicate pathogenic bacteria of choice while preserving an otherwise healthy microbiome in patients, and this collaboration with Janssen will enable us to further develop products on the platform to help patients in need around the world.”

CRISPR is a form of gene editing. Most companies have focused on using the technique to modify human genes to treat diseases, although that is largely in its earliest stages. The technique has been in the spotlight with the controversial announcement that Chinese researcher He Jiankui had used CRISPR-Cas9 to alter the DNA of embryos for seven couples, with the resultant birth of a set of twins and another pregnancy.

Locus’ approach is CRISPR-Phage (crPhage), which uses CRISPR and a different enzyme, Cas3. Phages are viruses that infect bacteria. Cas3 is actually the most common CRISPR-Cas system in nature, while CRISPR-Cas9 is relatively rare. Cas3 is more effective at shredding target DNA beyond any chance of repair.

In November 2017, Garofolo told FierceBiotech, “Selecting the right tool for the job at hand is critical for success. Both Cas3 and Cas9 are very capable solutions in their own rights, but Cas3 causes irreversible DNA damage—think Pac-Man chewing up the target bacteria’s DNA—resulting in cell death. As such, it is the overwhelming correct choice for an antibacterial product.”

Locus has several programs focused on E. coli for urinary tract infections and C. difficile for C. diff infections. The Janssen programs will apparently focus on respiratory and other infections.

The company also has a second area focused on microbiome-related diseases. These include programs relevant to inflammatory bowel disease (IBD) and other diseases caused by problems in the microbiome in gastrointestinal, immunology, oncology, and central nervous system therapy areas.

The company hopes to launch clinical trials sometime this year.

Locus raised $19 million in a Series A financing in late 2017. It was led by Artis Ventures with participation from Tencent Holdings, Abstract Ventures and the North Carolina Biotechnology Center. In January, Locus partnered with IDbyDNA to develop a companion diagnostic using its next-generation sequencing platform, Explify. The test will be used to help select patients for Locus’ LBx-PAO1 antimicrobial product that targets Pseudomonas aeruginosa. In July 2018, Locus acquired EpiBiome’s discovery platform, which allowed it to isolate bacteriophages more quickly.

https://www.biospace.com/article/locus-and-janssen-ink-potential-818-million-deal-to-develop-crispr-based-antibacterials/