Syndicate content

Archive

January 5th

Wave Life Sciences Reports 12.4% Reduction in Mutant Huntingtin Protein Using Allele-Specific Stereopure Antisense Oligo Targeted at SNP2 in Mutant Huntingtin Transcript; Reports Topline Data from Ongoing Trial & Plans to Initiate Higher-Dose Cohort

On December 30, 2019, Wave Life Sciences Ltd. (Nasdaq: WVE), a clinical-stage genetic medicines company committed to delivering life-changing treatments for people battling devastating diseases, today announced topline data from the ongoing Phase 1b/2a PRECISION-HD2 trial evaluating investigational therapy WVE-120102, designed to be the first allele-selective approach to treat Huntington’s disease (HD). In an analysis comparing all patients treated with multiple intrathecal doses of WVE-120102 to placebo, a statistically significant reduction of 12.4% (p<0.05) in mutant huntingtin (mHTT) protein was observed in cerebrospinal fluid (CSF). An analysis to assess a dose response across treatment groups (2, 4, 8, or 16 mg) suggested a statistically significant response in mHTT reduction at the highest doses tested (p=0.03). WVE-120102 was generally safe and well tolerated across all cohorts. These data support the addition of higher dose cohorts, and Wave expects to initiate a 32 mg cohort in January 2020. “This topline analysis has given us the opportunity to evaluate early data from our ongoing dose finding study. The data demonstrate a reduction in mutant HTT and a safety and tolerability profile that supports exploration of higher doses of WVE-120102, with the goal of maximizing mutant HTT reduction and avoiding a negative impact on the healthy huntingtin protein,” said Michael Panzara, MD, MPH, Chief Medical Officer of Wave Life Sciences. “We plan to initiate the 32 mg cohort imminently and look forward to sharing data in the second half of 2020.”

Roche Concludes Acquisition of Spark Therapeutics to Strengthen Presence In Gene Therapy

On December 17, 2019, Roche (SIX: RO, ROG; OTCQX: RHHBY) and Spark Therapeutics, Inc. (NASDAQ: ONCE) (“Spark”) announced the completion of the acquisition following the receipt of regulatory approval from all government authorities required by the merger agreement. Commenting on this important step forward, Severin Schwan, CEO of Roche, said, “We are excited about this important milestone because we believe that together, Roche and Spark will be able to significantly improve the lives of patients through innovative gene therapies. This acquisition supports our long-lasting commitment to bringing transformational therapies and innovative approaches to people around the world with serious diseases.” Spark Therapeutics, based in Philadelphia, Pennsylvania, is a fully integrated, commercial company committed to discovering, developing, and delivering gene therapies for genetic diseases, including blindness, hemophilia, lysosomal storage disorders, and neurodegenerative diseases. Spark Therapeutics will continue to operate as an independent company within the Roche Group. “Today ushers in a new and promising era in the development of genetic medicines for patients and families living with inherited diseases and beyond,” said Jeffrey D. Marrazzo, Co-Founder and CEO of Spark Therapeutics. “Spark and Roche share an ethos of imagining the unimaginable. Together, we have the potential to change the future of medicine and deliver the medicines of tomorrow today. We couldn’t be more thrilled about what’s next.” Roche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve people’s lives.

January 4th

Amazing Finding: Eye-Less Red Brittle Star Can See; Only Second Example in All of Biology of Animal Able to See Without Eyes; Deep Red Daylight Pigment of Color-Changing Brittle Star Is Key to Enabling Vision

Scientists have shown for the first time that brittle stars use vision to guide them through vibrant coral reefs, thanks to an unusual color-changing trick. The international team, led by researchers at Oxford University Museum of Natural History, described a new mechanism for vision in the red brittle star Ophiocoma wendtii, a relative to sea stars and sea urchins, which lives in the bright and complex reefs of the Caribbean Sea. The team’s findings were published online on January 2, 2020 in Current Biology. The open-access article is titled “Extraocular Vision in a Brittle Star Is Mediated by Chromatophore Movement in Response to Ambient Light.” This species first captured scientific attention more than 30 years ago thanks to its dramatic change in color between day and night and its strong aversion to light. Recently, researchers demonstrated that O. wendtii was covered in thousands of light-sensitive cells, but the exact behaviors these cells control remained a mystery. The new research shows that O. wendtii is able to see visual stimuli, and that its signature color-change might play an important role in enabling vision. Lauren Sumner-Rooney, PhD, a research fellow at Oxford University Museum of Natural History who studies unusual visual systems, has been working with Ophiocoma for several years at the Smithsonian Tropical Research Institute in Panama and the Museum für Naturkunde in Berlin. Alongside team members from the Museum für Naturkunde, Lund University (Sweden), and the Georgia Institute of Technology (USA), Dr. Sumner-Rooney ran hundreds of behavioral experiments to test the brittle stars' “eyesight.”

Researchers Identify Positions of All Atoms in Clostridium difficile’s Binary Toxin; Results May Serve As Starting Point for Effective Drug Design for Treatment of Often Deadly Bacterial Infection

An open-access article published online on January 2, 2020 in PNAS details a research breakthrough that provides a promising starting point for scientists to create drugs that may cure Clostridium difficile (C. diff) infection-- a virulent health care-associated infection that causes severe diarrhea, nausea, internal bleeding, and potentially death. The article is titled “Structure of the Cell-Binding Component of the Clostridium Difficile Binary Toxin Reveals a Di-Heptamer Macromolecular Assembly.” The C. diff bacteria affects roughly half-a-million Americans and causes nearly 15,000 deaths in the U.S. annually, and results in over $5 billion in health-care-related costs each year in this country. Overuse of antibiotics has increasingly put patients in heath care facilities at risk for acquiring C. diff and made some strains of the bacteria particularly hard to treat. But newly discovered information about a type of toxin released by the most dangerous strains of C. diff is providing researchers with a map for developing drugs that can block the toxin and prevent the bacteria from entering human cells. "The most dangerous strains of C. diff release a binary toxin (image) that first binds to cells and then creates a pore-forming channel that allows the toxin to get inside and do harm," said Amedee de Georges, PhD, the study's principal investigator and a professor with the Advanced Science Research Center at The Graduate Center, CUNY's Structural Biology Iniative. "We were able to combine several increasingly popular biophysical imaging techniques to visualize and characterize every atom of this binary toxin and show us where they are positioned. These details provide a critical and extremely useful starting point for designing drugs that can prevent C.

Water Lily Genome Expands Picture of the Early Evolution of Flowering Plants

The newly reported genome sequence of a water lily sheds light on the early evolution of angiosperms, the group of all flowering plants. An international team of researchers, including scientists at Penn State, used high-throughput next-generation sequencing technology to read out the water lily's (Nymphaea colorata) genome and transcriptome (the set of all genes expressed as messenger RNAs). The unusual high quality and depth of coverage of the sequence allowed the researchers to assemble the vast majority of the genome into 14 chromosomes and identify more than 31,000 protein-coding genes. An open-access paper describing the sequence and subsequent analysis was published online on December 18, 2019 in the journal Nature. "Water lilies have been an inspiration to artists like Claude Monet because of their beauty and important to scientists because of their position near the base of the evolutionary tree of all flowering plants," said Hong Ma, PfD, Associate Dean for Research and Innovation, Huck Distinguished Research Professor of Plant Molecular Biology, and Professor of Biology at Penn State, one of the leaders of the research team. "I previously contributed to the sequencing and analysis of the genome of Amborella, which represents the earliest branch to separate from other flowering plants, but Amborella lacks big showy colorful flowers and attractive floral scent, both of which serve to attract pollinators in most groups of flowering plants.

New Photodynamic Therapy Based on Photosensitizers (Photosens and Photodithazine) Induces Immunogenic Cell Death in Mouse Tumor Cells

The world scientific community is waging a difficult and prolonged war on cancer. New research in the field of immunogenic cell death can extend the area of drugs application and ensure patients' protection from relapse after therapy. Cancer treatment is not just the removal of the tumor cells from the body, and chemotherapy. The doctors' aim is to provide a scenario that would prevent tumor cells from proliferating and causing a new disease. For many years, scientists at the Lobachevsky State University of Nizhny Novgorod and the University of Ghent (Belgium) have been engaged in research aimed to minimize the harm to the body after cancer treatment and have been looking for new approaches to treating cancer patients. The project, supported by a grant from the Russian Science Foundation and headed by Dmitry Krys'ko, PhD, leading researcher of the Lobachevsky University's Institute of Biology and Biomedicine, Professor at Ghent University, has yielded its first major results. According to Professor Krys'ko, the existing anti-cancer therapy (chemotherapy, radiation therapy and photodynamic therapy) causes great damage to the body as a whole, while his team's research is aimed at the stimulation of immunogenic cell death, which not only minimizes the damage, but also enhances the efficacy of treatment by involving the body's resources in the fight against cancer. "In this study, we tested some drugs for anticancer therapy based on photodynamic treatment and investigated their new immunogenic properties. We can say that not only the external impact will be used to fight cancer, but also the body itself will engage in the fight by triggering the reactions of the adaptive immune response.

December 20th, 2019

Ratio of Neutrophils to T Cells in Tumor Environment Can Help Predict Which Patients Will Respond to Checkpoint Inhibitor Immunotherapy in Lung Cancer; Study Suggests That Neutrophil-Blocking Drugs May Boost Effectiveness of Checkpoint Inhibitors

For many lung cancer patients, the best treatment options involve checkpoint inhibitors. These drugs unleash a patient's immune system against their disease and can yield dramatic results, even in advanced cancers. But checkpoint inhibitors come with a huge caveat: They only help a small subset of patients. Doctors struggle to predict who these patients are and -- just as important -- who they aren't. Results from a new study published online on December 18, 2019 in JCI Insight could help improve those forecasts. The open-access article is titled “Neutrophil Content Predicts Lymphocyte Depletion and Anti-PD1 Treatment Failure In NSCLC.” After analyzing tumor samples from 28 patients with non-small cell lung cancer(NSCLC), researchers linked a common immune cell with treatment failure. The culprit: neutrophils, the most abundant type of white blood cell. The paper shows that the balance between neutrophils and another type of immune cell -- disease-fighting T cells -- could accurately predict which patients would respond or not. If more neutrophils than T cells were crowded into a tumor, the drugs did not curb the patients' cancers. But if the balance was reversed, checkpoint inhibitors revved up patients' immune systems against their disease. "The study is the first to implicate neutrophils in the failure of checkpoint inhibitors," said senior author Dr. McGarry Houghton, MD, a lung cancer immunologist at Fred Hutchinson Cancer Research Center in Seattle, Eashington. "Our findings also hint at a way to help patients who have this cellular signature." In a mouse model of NSCLC, the researchers administered a drug that decreased the number of neutrophils in and around tumors. That, in turn, boosted the efficacy of checkpoint inhibitors -- T cells now had a clear path to attack diseased cells in the mice.

December 20th

Combination of Chemo Drug (Imatinib) and Diabetes Drug (Metformin) Shows Potential for Treating Ewing Sarcoma

Ewing sarcoma, an aggressive tumor that commonly affects bones in adolescents and young adults, is diagnosed in approximately 225 American children and teens every year, accounting for about 1 percent of pediatric cancers. Although Ewing sarcoma has been studied for decades, it has no effective cure and a survival rate of just 20-30% for patients who relapse; furthermore, most treatments require surgical resections or amputation and this impacts quality of life of the patients. But a research team at Houston Methodist aims to change those odds. A new possibility for treatment is proposed by Stephen Wong (photo), PhD, John S. Dunn Sr. Presidential Distinguished Chair in Biomedical Engineering and Professor of Computer Science and Bioengineering in Oncology at Houston Methodist. He is proposing a combination of two well-known drugs as a new treatment option for Ewing sarcoma--the chemotherapy drug imatinib and the diabetes drug metformin. A report describing the research of Dr. Wong and colleagues on this possible treatment option was published in the January 2020 issue of Cancer Letters. The article is titled “Imatinib Revives the Therapeutic Potential of Metformin on Ewing Sarcoma by Attenuating Tumor Hypoxic Response and Inhibiting Convergent Signaling Pathways.”

[Press release] [Cancer Letters abstract]

Triplet Therapeutics Launches with $59 Million in Financing to Further Its Development of Transformative Treatments for Triplet Repeat Disorders; Company Targets DNA Damage Repair (DDR) Pathway in Huntington’s Disease and Nearly 40 Other Diseases

On December 17, 2019, Triplet Therapeutics, Inc., a biotechnology company harnessing human genetics to develop treatments for repeat expansion disorders at their source, launched today with $59 million in financing including a $49 million Series A financing led by MPM Capital and Pfizer Ventures U.S. LLC, the venture capital arm of Pfizer Inc. (NYSE: PFE). Atlas Venture, which co-founded and seeded Triplet with a $10 million investment, also participated in the Series A financing, alongside Invus, Partners Innovation Fund and Alexandria Venture Investments. Triplet Therapeutics was founded in 2018 by Nessan Bermingham, PhD, a serial biotech entrepreneur and venture partner at Atlas Venture, along with Atlas Venture and Andrew Fraley, PhD, to pursue a transformative approach to developing treatments for repeat expansion disorders, a group of more than 40 known genetic diseases associated with expanded DNA nucleotide repeats. A significant body of human genetic evidence has identified that one central pathway, known as the DNA damage response (DDR) pathway, drives onset and progression of this group of disorders, which include Huntington’s disease, myotonic dystrophy, and various spinocerebellar ataxias. Triplet is developing antisense oligonucleotide (ASO) and small interfering RNA (siRNA) development candidates to precisely knock down key components of the DDR pathway that drive repeat expansion. This approach operates upstream of current approaches in development, targeting the fundamental driver of these diseases. By precisely reducing activity of select DDR targets, Triplet’s approach is designed to halt onset and progression across a wide range of repeat expansion disorders. The company has a fully assembled senior management team of industry veterans.

December 19th

Cryo-EM & Supercomputer Analyses Reveal Asymmetry in Active Sites of B-Raf Kinases; Possible Key Clue to Solving Melanoma Mystery

It starts off small, just a skin blemish. The most common moles stay just that way -- harmless clusters of skin cells called melanocytes, which give us pigment. In rare cases, what begins as a mole can turn into melanoma, the most serious type of human skin cancer because it can spread throughout the body. Scientists are using powerful supercomputers to uncover the mechanism that activates cell mutations found in about 50 percent of melanomas. The scientists say they're hopeful their study can help lead to a better understanding of skin cancer and to the design of better drugs. In 2002, scientists found a link between skin cancer and mutations of B-Raf (Rapidly Accelerated Fibrosarcoma) kinase (image), a protein that's part of the signal chain that starts outside the cell and goes inside to direct cell growth. This signal pathway, called the Ras/Raf/Mek/Erk kinase pathway, is important for cancer research, which seeks to understand out-of-control cell growth. According to the study, approximately 50 percent of melanomas have a specific single mutation on B-Raf, known as the valine 600 residue to glutamate (V600E). B-Raf V600E thus became an important drug target, and specific inhibitors of the mutant were developed in the following years. The drugs inhibited the mutant, but something strange happened. Paradoxically, quieting the mutant had a down side. It activated the un-mutated, wild-type B-Raf protein kinases, which again triggered melanoma. "With this background, we worked on studying the structure of this important protein, B-Raf," said Yasushi Kondo, PhD, a postdoctoral researcher in the John Kuriyan Lab at UC Berkeley. Dr.