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/

Takeda Drives Immuno-Oncology With Three Cell Therapy Collaborations

Takeda Pharmaceutical has started 2019 with a spate of cell therapy collaborationsdesigned to advance the company’s novel immuno-oncology portfolio. The three collaborations will accelerate the discovery of next-generation cancer immunotherapies.

This morning, Osaka, Japan-based Takeda struck deals with Memorial Sloan Kettering Cancer Center, Noile-Immune Biotech Inc. and Crescendo Biologics. Takeda said the diversification into next-generation cell therapy builds directly on its three strategic pillars in oncology: hematologic malignancies, lung cancer and immuno-oncology.

Phil Rowlands, head of Takeda’s Oncology Therapeutic Area Unit, said the company has been excited by momentum in oncology research and development, specifically around the “curative potential of cell-based therapies.” Rowland said the company looks forward to collaborating with pioneers in the field of cell therapy to “fuel research and discovery with the aim of targeting novel mechanisms of action in the cancer-immunity cycle to help us fulfill our aspiration to cure cancer.”

In its partnership with Memorial Sloan Kettering, Takeda will work to develop novel chimeric antigen receptor T-cell (CAR-T) products for the treatment of multiple myeloma, acute myeloid leukemia and additional solid tumor indications. The collaboration with the famed cancer center will be co-led by former Juno Therapeutics scientific founder Michel Sadelain, who is currently head of the Center for Cell Engineering at Memorial Sloan Kettering.

In September of 2017, Takeda and biotech startup Noile-Immune Biotech forged a deal to develop CAR-T therapies, shortly after the U.S. Food and Drug Administration approved the first CAR-T therapy, Novartis’ Kymriah. This morning, Takeda and Noile-Immune have strengthened their relationship. The company noted that the successes seen so far in the program have spurred the move. Takeda exclusively licensed two assets, NIB-102 and NIB-103 for the treatment of various solid tumor indications. The company will co-develop these CAR-T programs with Noile, using that company’s proprietary “Prime” (proliferation inducing and migration-enhancing) CAR-T platform. The company plans to gain regulatory approval for human testing of NIB-102 by the end of this year.

In its third deal with Crescendo Biologics, Takeda will exercise its option for an exclusive oncology-targeted Humabody license to allow the company to evaluate the Humabody VHs for the development of novel CAR-T therapeutics. Takeda said the development will “leverage the unique properties of single-domain tumor-targeted binders as an alternative to conventional single-chain variable fragment (scFv)-based approaches.”

In addition to the collaborations, Takeda also established a new internal translational cell therapy engine with bioengineering, chemistry, manufacturing and control (CMC), clinical and translational expertise. This new division will be led by Stefan Wildt. The group will aim to “rapidly translate innovative and differentiated cell therapy concepts into the clinic,” Takeda said.

Wildt said there’s an incredible opportunity to combine promising innovation through external partners with “the power of a fit-for-purpose translational cell therapy engine” that will accelerate the development of novel therapies.

https://www.biospace.com/article/takeda-drives-immuno-oncology-portfolio-with-three-cell-therapy-collaborations/

Unity Biotechnology selects UBX1967 as lead ophthalmology candidate

Unity Biotechnology has selected UBX1967 as the lead development candidate in the ophthalmology pipeline for advancement into studies to enable an Investigational New Drug application and executed the compound license agreement for the compound with Ascentage Pharma under a previously agreed compound library agreement. UBX1967 is being evaluated in a range of age-related diseases of the eye, including neovascular age-related macular degeneration, proliferative diabetic retinopathy and diabetic macular edema. Unity plans to file an IND application for UBX1967 in 2H19.
https://thefly.com/landingPageNews.php?id=2843517

Catalyst Biosciences initiated at Oppenheimer

Catalyst Biosciences initiated with Outperform at Oppenheimer. Oppenheimer analyst Kevin DeGeeter initiated Catalyst Biosciences with an Outperform rating and a price target of $24. The analyst notes that the company offers a “unique approach” in hemophilia treatment, asking key questions about the “best method to transition inhibitor patients from products designed to treat bleeding to prophylaxis for preventing bleeds” and the optimal treatment of “pediatric hemophilia B patients that are not candidates for subcutaneous non-factor replacement therapies or gene therapy”. DeGeeter contends that investors are under-appreciating Catalyst Biosciences’ Factor VIIa program and anticipates the investment story for the stock to solidify this year.
https://thefly.com/landingPageNews.php?id=2843503

Novavax spikes as high as 12% after announcing positive results for NanoFlu

Shares of Novavax are spiking in the after-hours after announcing top-line results of its Phase 2 clinical trial of NanoFlu. The trial compared the safety and immune responses of various quadrivalent formulations of NanoFlu, with or without Novavax' Matrix-M adjuvant, with two U.S.-licensed influenza vaccines in 1,375 healthy adults 65 years of age and older. Shares are currentlu up 9.5% in after-hours trading to $2.23 per share.
https://thefly.com/landingPageNews.php?id=2843511