Category Archives: Genetic medicine

News Release

Wednesday, September 9, 2020

An experimental treatment for eczema that aims to modify the skin microbiome safely reduced disease severity and increased quality of life for children as young as 3 years of age, a National Institutes of Health study has found. These improvements persisted for up to eight months after treatment stopped, researchers report Sept. 9 in Science Translational Medicine.

Atopic dermatitis, commonly called eczema, is a chronic inflammatory skin disease characterized by dry, itchy skin and rashes. The disease is most common in children and is linked to an increased risk of developing asthma, hay fever and food allergy. While available treatments can help manage eczema symptoms, current options can be costly, and many require multiple daily applications.

The experimental therapy contains strains of live Roseomonas mucosaa bacterium naturally present on the skinoriginally isolated from healthy volunteers and grown under carefully controlled laboratory conditions. For four months, clinical trial participants or their caregivers periodically applied this probiotic therapy to areas of skin affected by eczema.

A child suffering from eczema, which can be itchy, painful and distracting for the child, also is very difficult for the entire family, said Anthony S. Fauci, M.D., director of NIHs National Institute of Allergy and Infectious Diseases (NIAID), which led the study. These early-stage findings suggest that R. mucosa therapy may help relieve some children of both the burden of eczema symptoms and the need for daily treatment.

Numerous genetic and environmental factors contribute to eczema, and scientists are learning more about the role that the skins microbiome plays in this condition. In 2016, NIAID researchers reported that R. mucosa strains isolated from healthy human skin improved outcomes in cell culture and mouse models of eczema.

To build on these preclinical findings, NIAID launched a Phase 1/2 clinical trial at the NIH Clinical Center in Bethesda, Maryland, to assess the safety and potential benefit of R. mucosatherapy in people with eczema. Interim results reported in 2018 for 10 adults and five children aged 9 to 14 years indicated that the treatment was safe and associated with reduced eczema severity. Since then, the trial has enrolled an additional 15 children, for a total of 20 children with mild to severe eczema ranging in age from 3 to 16 years.

Twice weekly for three months and every other day for an additional month, children or their caregivers sprayed a solution of sugar water containing liveR. mucosaonto areas of skin with eczema. For the first 15 children enrolled in the study, the dose of live R. mucosa was gradually increased each month. The last five children to enroll received the same dose throughout the four-month treatment period. Regardless of dosing strategy, no serious adverse events were attributed to the therapy.

Most children in the study experienced substantial improvements in their skin and overall wellbeing following R. mucosa therapy. Encouragingly, the therapeutic bacteria stayed on the skin and continued to provide benefit after therapy stopped, said NIAIDs Ian Myles, M.D., principal investigator of the trial. These results support a larger study to further assess the safety and effectiveness of this experimental treatment by comparing it with a placebo.

Seventeen of the 20 children experienced a greater than 50% improvement in eczema severity following treatment. Improvement occurred on all treated skin sites, including the inner elbows, inner knees, hands, trunk and neck. The scientists also observed increases in the skins barrier functionits ability to seal in moisture and keep out allergens. Additionally, most children needed fewer corticosteroids to manage their eczema, experienced less itching, and reported a better quality of life following the therapy. These benefits persisted after treatment ended, and the therapeutic R. mucosa strains remained on the skin for up to eight months.

The NIAID researchers next set out to better understand how R. mucosa therapy improves eczema symptoms. They found that treated skin had increased microbial diversity and reduced levels of Staphylococcus aureusa bacterium known to exacerbate eczema.

In addition to imbalances in the microbiome, the skin of people with eczema is deficient in certain lipids, or oils. By conducting experiments in cell and animal models of eczema, the NIAID scientists found that a specific set of lipids produced by R. mucosa strains isolated from healthy skin can induce skin repair processes and promote turnover of skin tissue. Study participants had increased levels of these lipids on their skin after treatment with R. mucosa.

The researchers emphasize that additional studies are needed to further elucidate the mechanism of R. mucosa therapy and to explore whether genetic or other factors may explain why some participants did not benefit from the experimental treatment.

For more information about the completed Phase 1/2 study Beginning Assessment of Cutaneous Treatment Efficacy forRoseomonasin Atopic Dermatitis (BACTERiAD), see ClinicalTrials.gov using identifier NCT03018275.

NIH has exclusively licensed the R. mucosa therapy to Forte Biosciences to advance this potential treatment through further clinical development,and the company plans to begin enrollment in a Phase 2 placebo-controlled trial later this month. For more information about this study, Evaluation of FB-401 in Children, Adolescents and Adults (2 Years and Older) With Mild to Moderate Atopic Dermatitis, see ClinicalTrials.gov using identifierNCT04504279.

NIAID conducts and supports researchat NIH, throughout the United States, and worldwideto study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIHTurning Discovery Into Health

IA Myles et al. Therapeutic responses to Roseomonas mucosa in atopic dermatitis may involve lipid-mediated TNF-related epithelial repair. Science Translational Medicine DOI: 10.1126/scitranslmed.aaz8631 (2020).

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Probiotic skin therapy improves eczema in children - National Institutes of Health

KING OF PRUSSIA, Pa.--(BUSINESS WIRE)--Genomind, the leader in comprehensive genetics and digital mental health services, has pioneered a new level of specificity and accuracy for cheek swab-based pharmacogenetics tests.

Genominds Professional PGx Express test provides clinicians with a comprehensive report of up to 24 genes that delivers important prescribing guidance designed to help reduce the traditional process of trial and error with mental health medications. Genomind has served over 15,000 clinicians and tested over 270,000 patients for this important treatment guidance. The FDA includes pharmacogenetic biomarker warnings, precautions and drug-drug interaction guidance on the labels of over 270 medications (https://www.fda.gov/drugs/science-and-research-drugs/table-pharmacogenomic-biomarkers-drug-labeling).

Two of the most important genetic variants which Genominds Professional PGx Express tests for are HLA-B *15:02 and HLA-A*31:01. These genes are part of the complex human leukocyte antigen (HLA) system that is among the most highly variable DNA regions in humans and is central to autoimmune diseases and transplant rejection. Both of these variants are associated with an increased risk of serious, sometimes fatal, skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis, in the presence of carbamazepine (as well as oxcarbazepine and phenytoin for HLA-B*15:02).

Carbamazepine is indicated for the treatment of epilepsy and trigeminal neuralgia, and is commonly used for individuals with mood disorders, such as bipolar disorder. It is on the World Health Organizations List of Essential Medicines1 and was prescribed over 3.5 million times in 2019, a number that experts say will increase in 20202.

In contrast to HLA-B*15:02, the HLA-A* 31:01 allele is more common in Caucasians, while also occurring in individuals of Hispanic/South American and East Asian descent. Carbamazepines FDA label contains warnings about this gene-drug pair, as does the Clinical Pharmacogenetic Implementation Consortium (CPIC).

Until recently, commercial PGx assays commonly tested for this allele using a surrogate tag SNP (single nucleotide polymorphism) method. During a recent validation exercise, Genomind identified a very high false positive rate of approximately 40%, with this common industry method. This means with the traditional testing method, 40% of the positive tests would incorrectly identify someone as being at risk of serious adverse events with carbamazepine treatment, thereby inappropriately excluding a potentially useful agent.

Genominds CEO Shawn OBrien was inspired to find a better solution. Our company is all about our I-CAIRE culture (integrity, collaboration, accountability, innovation, respect and excellence), so when we discovered this shortcoming in the industry, we immediately set about finding a better solution to help more clinicians and patients.

Genomind scientists, led by CSO Dr. David Robbins, developed an innovative and proprietary real-time PCR (polymerase chain reaction) test that is highly specific for HLA-A*31:01. The increased specificity of this assay also makes the need for confirmatory testing unnecessary for individuals testing positive. In validation testing of this new and improved assay, specificity and sensitivity were 100%. In real-world testing we expect specificity to be >99%. This means we will be able to reduce the 40% of false positives down to a fraction of a percentage3. This PCR-based testing was validated by comparing random anonymized patient samples with HLA typing by Next Generation Sequencing (NGS) through a third party lab. FDA considers NGS as the gold standard for HLA typing. The validation was further supported by testing samples from the Coriell Institute for Medical Research with documented rare and common HLA-A types. Genomind filed a patent on this important breakthrough and is the only comprehensive mental health genetics test with this capability on the market.

This novel innovation uniquely provides much greater accuracy in identifying patients at risk for a serious drug reaction and provides greater and safer access of a potentially helpful medication, carbamazepine, for individuals previously thought to be at risk said Dr. Scott Aaronson, MD, Clinical Assistant Professor of Psychiatry at the University of Maryland School of Medicine and Distinguished Fellow of the American Psychiatric Association.

With Medicares recently published new Local Coverage Determination allowing coverage of tests like Genominds, and with United Healthcares positive coverage policy, the Mental Health PGx industry is expected to see major growth. Therefore, it is critical that clinicians have access to the most accurate and specific PGx results.

To this end Genomind is offering a major national digital education effort for clinicians and patients. They are starting with their 15,000 clinicians and providing education materials, access to their acclaimed On-Demand Hotline or scheduled consults, and free access to their state-of-the-art precision medication management software, G-DIG (Genomind Drug Interaction Guide.) Genomind will also be reaching tens of thousands of the highest prescribers of mental health medications and millions of potential patients with their digital communications engine that generates millions of hits and video views on their website annually. Genomind is offering all their advanced services and software to any new registering clinician.

About Genomind

Genomind is a leading precision mental health company singularly focused on filling the innovation gap in mental health care through novel, genetics-based tools. Supported by a world-class genetics lab, a unique heritage of clinical mental health expertise, clinical collaboration and consultation, state-of-the-art digital tools and telemental health enabling services, Genomind is empowering a new standard of care. Its flagship product, Genomind Professional PGx Express, is the most comprehensive pharmacogenetic testing service helping medical professionals personalize patients mental health treatment. The Company also recently launched Genomind Mental Health Map a breakthrough direct-to-consumer test that enables a new and better understanding of the biological basis of mental wellness, coupled with personalized actionable guidance to help people improve health and wellness. Learn more at http://www.genomind.com.

(1) World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.

(2) "Carbamazepine - Drug Usage Statistics". ClinCalc. Retrieved 11 April 2020.

(3) This fraction of a percent represents the real world use HLA-A*31 types other than 31:01 (ie. HLA-A*31:04, 31:12, and 31:16) which may rarely cause false positive results. That being said, it is not known if these types are associated with skin disorders following use of carbamazepine.

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Genomind Announces Major Industry-Leading HLA-A Test Innovation on its Comprehensive Mental Health Pharmacogenetics (PGx) Test, Increasing Utility for...

Vijay Reddy was seeking a return to the US when he left his role as CMO at London-based Autolus this summer. Philadelphia is that landing spot, as the T cell immunotherapy player Tmunity has put him in charge of R&D.

Reddy arrives at the Penn spinout with plenty of Big Pharma bona fides after developing the CAR-T cell clinical program at Autolus. Tmunitys new chief R&D officer was a senior director and led early clinical development at J&J subsidiary Janssen from 2013-16, and from 2009-13, he was GSKs medical director, cancer research and clinical development.

Tmunity also added to their leadership team by selecting Simona King as their CFO. A nearly 20-year vet of Bristol Myers Squibb in various financial roles, King just had a brief run as VP, finance and assistant treasurer at Emergent BioSolutions.

Co-founded by CAR-T inventors Carl June and Bruce Levine, Tmunity has racked up $231 million in total funding.

Completing a 4-year run as CFO at Agios, Andrew Hirsch has made the jump to CEO of protein degradation pioneer C4 Therapeutics. Hirsch takes the helm at another biotech after a brief tenure as president and CEO of Bind Therapeutics, where he spent 4 years overall. C4 just penciled in $100 million for an IPO and back in June, the biotech raked in a $170 million raise, $150 million of that from a Series B round. Hirsch succeeds Andrew Phillips, who bolts after 2 years on the job.

Maryland-based CavoGene LifeSciences, whose lead program for ALS is slated for clinical trials by early 2022, has a new CEO with Daniel Jorgensen now at the helm. A former senior director at Pfizer, Jorgensen was the pharma giants first vaccine development team leader, and he also served as global clinical leader for azithromycin. Elsewhere, hes been CMO and SVP, clinical development at PolyMedix and VP, clinical research for AMAG Pharmaceuticals.

Ex-Dendreon CEO Jim Caggiano is back at the helm of another biotech, this time at Targazyme, an immunotherapy and stem cell transplantation outfit in San Diego using enzyme-based platform technologies. Before Caggianos tenure at Dendreon, the former US Army officer was president of Valeant Pharmaceuticals and also held positions at Allergan for more than 5 years.

No doubt getting a boost from Akebias Phase III vadadustat fail last week, roxadustat developer FibroGen has plucked Big Pharma vet Percy Carter from Janssen for the newly-created CSO post. Carter was previously Janssens global head of discovery sciences, and prior to that, he spent nearly 20 years at Bristol Myers Squibb in several roles, namely head of discovery and head of discovery chemistry & molecular technologies.

Young oncology company Black Diamond Therapeutics, which collected over $200 million for their IPO in January, has locked in Rachel Humphrey as CMO. Humphrey is taking over from Karsten Witt, who has been serving as acting CMO along with his duties as the companys SVP of clinical development. Humphrey brings to the table experience from a long list of roles at CytomX Therapeutics where she served as CMO Eli Lilly, AstraZeneca, Mirati Therapeutics, Bristol Myers Squibb and Bayer.

Ali Fattaey is now leading cancer metabolism player MetaboMed as their CEO. His predecessor, co-founder Simone Botti, is moving to a senior position at an undisclosed European VC. Fattaey previously led therapeutics discovery and development at Scipher Medicine and was the president and CEO at Curis. He started his career at Onyx Pharmaceuticals as VP, research.

Some hard times have befallen DBV Technologies, whose peanut allergy skin patch was rebuffed in a CRL from the FDA in August. Now, a couple of execs have headed for the exits with CFO Ramzi Benamar and CCO Kevin Trapp walking out the door of the French biotech. Sbastien Robitaille will be filling in as CFO on an interim basis effective Oct 2. The Ipsen vet, who started out at DBV 5 years ago as SVP, group controller and information systems, was promoted to chief of staff to CEO Daniel Tass a year ago.

Molly Henderson is resigning from her role as CFO at Princeton, NJ biotech Advaxis, effective Sept 25, to become CFO at UroGen beginning the following week. President and CEO Kenneth Berlin will function as interim CFO until her replacement is found. Advaxis has had a rough go of it with its ill-fated Amgen partnership and multiple FDA holds on their lead asset axalimogene.

Elsewhere at UroGen, Polly Murphy has taken on the role of CBO and Jason Smith will be general counsel and chief compliance officer. Murphy and Smith are both Pfizer alums: Murphy spent 12 years in a series of VP roles at the pharma giant and was most recently their VP for early commercial development in the oncology business unit, while Smith logged 11 years at Pfizer, the last 4 of those as their chief counsel, oncology. Before that, Smith was legal lead for the North American region of Pfizer Essential Health.

Back in May, Spruce Biosciences introduced Samir Gharib as their CFO, and theres another change at the San Francisco biotechs C-suite with Rosh Dias coming in as CMO. Before joining Spruce, which targets rare endocrine disorders and revealed positive Phase II data a year ago with lead candidate tildacerfont, Dias a Novartis vet spent the last year in the same role at Indivior. From 2015-18, he was Amgens VP, global scientific affairs. In other Spruce developments, ex-BioMarin CFO Dan Spiegelman was added to their board of directors.

Forging ahead in Phase III of their Covid-19 vaccine and ranking No. 2 on our list of the 29 vaccine players, Moderna has tapped Michael Mullette as managing director, Canada. After nearly 2 decades at Sanofi, with the last 2 years as general manager and country chair for Sanofi Canada in Montreal, Mullette came to Moderna in August as VP, market access, and he will carry on in that role in addition to his new appointment.

Raising $16 million in a Series B last week in an effort to democratize biologics, Seattle-based Lumen Bioscience has given the nod to Mike Spigarelli to be their CMO. Spigarelli is coming off 4 years as VP, medical affairs for diagnostics company Immucor.

Respiratory disease-centered genetic medicines player ReCode Therapeutics has a trifecta of appointments with Mukul Agarwal, CBO; Vladimir Kharitonov, SVP, chemistry, manufacturing and controls (CMC); and Brandon Wustman, SVP, R&D. Agarwal heads to ReCode after a little over a year as VP, corporate development at Forty Seven, which Gilead bought in March for $4.9 billion. Kharitonov had spent 20 years at Pacira Pharmaceuticals, the last 10 as their VP of R&D. And Wustman had been with the company as VP of R&D before ReCode joined forces with TranscripTx in March. From 2002-14, he was senior director, preclinical biology at Amicus Therapeutics.

Ex-Millipore chairman, president and CEO Martin Madaus is making his way to Feng Zhangs CRISPR-based diagnostics player Sherlock Biosciences as COO. Madaus has been interim CEO and executive chairman at Ultivue and Emulate Bio of late, and from 2014-19, he was chairman and CEO at Ortho Clinical Diagnostics.

UK clinical AI company Sensyne Health has tapped Michael Macdonnell as COO. Macdonnell currently heads Google Health as director of global deployment. Prior to his position at Google Health, Macdonnell was at Google DeepMind and held roles at Accenture, NHS England and Imperial College London among others.

Longtime Merck vet Ercem Atillasoy is on board at cell therapy company AlloVir as chief regulatory and safety officer. At Merck Research Laboratories, Atillasoy was VP and therapeutic area head of vaccines and infectious disease and VP, global regulatory affairs and clinical safety. He ran Keytrudas first IND filing for melanoma and was involved in the approval of such medicines as the Ebola vaccine Ervebo and the HPV vaccine Gardasil.

Tillman Gerngross new endeavor, Adagio Therapeutics, has locked in Eric Kimble as chief commercial officer and Ed Campanaro as SVP of clinical operations. Kimble and Campanaro worked at Cubist Pharmaceuticals in VP positions at the same time Kimble from 2004-13, and Campanaro from 2000-14. Before Adagio, which focuses on antibodies as an avenue to combat Covid-19, Kimble was the CCO at Entasis Therapeutics, while Campanaro was SVP of clinical operations at Artugen Therapeutics.

Olema Oncology, working on the development of targeted therapies for womens cancers, has made several new additions to its executive team with the appointment of Shane Kovacs as COO/CFO, Genentech vet Kinney Horn as CBO, and John Moriarty as EVP, chief legal officer. In addition, Pamela Klein has been named CMO and David Myles has been promoted to chief development officer. Kovacs joins the company from BlueRock Therapeutics (acquired by Bayer), where he served as CBO and CFO. Horn held a 16-year stint at Genentech, while Moriarty was most recently EVP and general counsel at Portola Pharmaceuticals.

Klein joins the company with experience from Syndax Pharmaceuticals and Genentech where she most recently served as VP, development among others. Myles moves up to his new role after serving as Olemas EVP, drug discovery and development.

New York-based Phosplatin Therapeutics, which has obtained exclusive license to a family of compounds known as phosphaplatins that may aid in treating cancer, has made Joseph ODonnell their interim CMO, and Jason Summa has gotten the call to be VP of clinical development. ODonnell has long been in academia at Dartmouth Universitys Geisel School of Medicine, where he started teaching in 1978. A Bind and Momenta alum, Summa was previously oncology director and clinical project scientist at Janssen.

Australian CRO Avance Clinical has corralled Jorgen Mould as a scientific affairs specialist. Mould was previously with Merck (KGaA) Healthcare as an associate medical manager and medical science liaison, neurology and immunology.

Cell engineering service provider MaxCyte has snagged Amanda Murphy as CFO, succeeding Ron Holtz who has been promoted to the position of SVP and chief accounting officer. Prior to MaxCyte, Murphy was managing director at BTIG and was partner and healthcare analyst at William Blair & Company.

BrainStorm Cell Therapeutics a developer of adult stem cell therapies for neurodegenerative diseases has recruited Bristol Myers Squibb vet Anthony Waclawski as EVP, global head of regulatory affairs. During his 35 year stint at Bristol Myers, Waclawski most recently served as the companys VP and head, regulatory and pharmaceutical sciences, cardiovascular, immunosciences, fibrosis and genetically-defined classes.

Prilenia Therapeutics, focused on treatments for neurodegenerative and neurodevelopmental disorders, has welcomed Henk Schuring as chief regulatory and commercialization officer. Schuring hails from Sanofi Genzyme, where he had a 21-year career and managed the rare nephrological diseases business and rare neurological diseases business.

Paul Bavier has been appointed general counsel at cancer-focused VelosBio, which racked up $137 million in a Series B round a couple months ago. Before he set off for VelosBio, Bavier spent 3 years at Avedro as their general counsel and chief compliance officer. He also held similar roles at Biodel from 2007-16 and was also their VP, corporate development.

With Rich Heyman now chairman of the board and a $70 million Series D in the hopper, NJ-based PMV Pharma has brought in Robert Ticktin as general counsel. Ticktin was previously associate general counsel, corporate at Tesaro (and then GSK after the buyout). PMV Pharma, which targets p53 mutations, has also selected Arena Pharmaceuticals CFO Laurie Stelzer to the board of directors as audit committee chair.

Sygnature Discovery, a Nottingham-based provider of drug discovery and preclinical services, has reeled in Andy Mead as director and head of drug abuse and substance use disorders at its integrated vivopharmacology company, RenaSci. Mead jumps aboard Sygnature from Sosei Heptares, where he served as director of discovery and translational safety. In addition, he brings experience from roles at Merck, Pfizer and AstraZeneca among others.

UKs PrecisionLife has appointed Simon Beaulah as SVP of healthcare and head of US operations. Most recently, Beaulah was director of healthcare at Linguamatics and prior to that was at IDBS Healthcare.

VC and growth equity firm SV has brought on Alex Badamchi-Zadeh as senior associate. Badamchi-Zadeh hops aboard with experience from Xilio Therapeutics where he helped guide the Kendall Square-based company through their $100.5 million Series B financing round and LEK Consulting.

Dean Mitchell has been named chairman of the board at Kinnate, which just nabbed a $98 million Series C in August. The GSK and Bristol Myers Squibb vet is the former president and CEO of Lux Biosciences and Alpharma.

Blueprint Medicines president and CEO Jeff Albers has joined the board of directors at Kymera Therapeutics. The newly public protein degradation player also added Replimune CBO Pamela Esposito to the board.

After penciling in a $150 million IPO in June, Forma Therapeutics has recruited Thomas Wiggans to its board of directors. Wiggans is the former chairman and CEO of Dermira (acquired by Eli Lilly) and helped in the formation of the Biotechnology Industry Organization, now Biotechnology Innovation Organization (BIO).

Bonnie Anderson has been elected to the board of directors at Bruker Corporation, a scientific instrument manufacturer. Anderson co-founded Veracyte in 2008 and is their chairman and CEO.

UK-based GW Pharmaceuticals has tapped ex-Incyte and Celgene CFO David Gryska to be on their board of directors. Gryska is also on the boards of Seattle Genetics, PDL BioPharma and Aerie Pharmaceuticals.

Joseph Bower has announced his decision to retire as chairman of the board at orthopedic-focused Anika Therapeutics after his term is up in 2021. Bower, a professor emeritus at Harvard Business School, has served on the board since 1993. Anika is also bringing in Jack Henneman and Stephen Richard as new board members.

AAV-based gene therapies-focused Prevail Therapeutics has added William Carson to its board of directors. Most recently, Carson served as president and CEO of Otsuka Pharmaceutical Development & Commercialization and draws from experience from a stint at Bristol Myers Squibb.

Hematology biotech Starton Therapeutics has chosen Kenneth Anderson and Asher Chanan-Khan to sit on their board of directors. Anderson is director of the Jerome Lipper Multiple Myeloma Center and LeBow Institute for Myeloma Therapeutics at Dana-Farber, while Chanan-Khan is a professor of medicine at Mayo Clinic Cancer Center in Jacksonville.

Retinal gene therapy company Gyroscope Therapeutics has brought on Sean Bohen to its board of directors.Bohen is the former CMO and EVP, global medicines development at AstraZeneca and previously served as SVP of Genentech early development (gRED).

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GSK and J&J alum Vijay Reddy to take control of R&D at Tmunity; Andrew Hirsch exits Agios for CEO job at C4 Therapeutics - Endpoints News

A blood test that can identify a variety of mutations in advanced breast cancer can reliably match women to effective targeted treatments, early results of a major clinical trial reveal.

The plasmaMATCH trial provides the strongest evidence yet that simple blood tests known as liquid biopsies can benefit women with breast cancer by tracking their disease as it evolves and directing them to the most effective treatments.

Researchers showed that the blood test is now reliable enough to be offered to patients on the NHS once it has passed approval, raising the prospect of a major reshaping of care that could speed up access to the best available drugs.

A team at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, analysed blood samples from more than 1,000 women with breast cancer that had recurred after treatment or spread to another part of the body. The aim was to see whether the blood test could help improve treatment for the significant proportion of women whose breast cancer is caused by one of a variety of rarer mutations as opposed to better-known defects like BRCA mutations.

The plasmaMATCH trial was largely funded by Stand Up To Cancer, a joint fundraising campaign from Cancer Research UK and Channel 4, with additional support from AstraZeneca, Breast Cancer Now and Puma Biotechnology Inc., and the new findings are published in TheLancet Oncologytoday (Thursday).

Researchers at The Institute of Cancer Research (ICR) and The Royal Marsden were able to reliably detect mutations found in tumour DNA that had been shed into the bloodstream of women with advanced breast cancer. They then went on to match patients to targeted treatments according to the specific mutations in the tumour DNA.

The researchers looked at three targetable defects in genes called HER2, AKT1 and ESR1, which are known to drive breast cancer. A total of 142 women with these detectable mutations were then given experimental drugs targeted against the specific characteristics of their cancer.

Women with ESR1 mutations were treated with fulvestrant, while women with HER2 mutations received neratinib on its own or with fulvestrant. Women with AKT1 mutations were split into two groups, according to whether their cancer was oestrogen receptor positive or not, and were treated with capivasertib plus fulvestrant, or with capivasertib on its own.

Researchers found that some women with HER2 and AKT1 mutations responded to the treatments assigned to them suggesting that liquid biopsies can successfully match patients with certain rare forms of advanced breast cancer to more effective treatments.

Five out of 20 women with rare HER2 mutations who were matched to neratinib saw a beneficial response meaning cancer growth was slowed or stopped, or tumours were shrunk.

Meanwhile, four out of 18 patients with AKT1 mutations responded to capivasertib. However, the treatment targeting the ESR1 mutation was not found to be effective.

Researchers also validated the findings by checking tissue samples from the patients to confirm that the liquid biopsies had correctly identified the presence or absence of the mutations in over 93% of cases sufficiently accurate to implement in routine care.

The team believes that findings from the plasmaMATCH trial will help make a strong case for the adoption of liquid biopsies into clinical practice for patients with advanced cancer a case strengthened by the fact that liquid biopsies are easier to take, faster to analyse and less painful for patients than standard tissue biopsies.

Liquid biopsies also offer a more dynamic alternative that could keep track of cancers as they evolve over time and their range of mutations changes.

For the targeted drugs that have shown initial promise in this study, the next step is to carry out larger clinical trials to assess whether they are better than existing treatments. The hope is that larger trials will lead to more targeted treatments being approved, providing new treatment options for patients with rare subtypes of breast cancer.

Study leader Professor Nick Turner, Professor of Molecular Oncology at The Institute of Cancer Research, London, and Head of the Ralph Lauren Centre for Breast Cancer Research at The Royal Marsden, said:

Our findings show that simple blood tests can quickly and accurately tell us the genetic changes present in a patients cancer, and use that information to select the most suitable available treatment.

Using a liquid biopsy could be particularly important for patients with advanced breast cancer, to help select the most appropriate treatment.

Tests that detect tumour DNA in the blood have huge potential and could transform how doctors select targeted therapies for patients with advanced cancer. Our study shows that these liquid biopsies can pick up the mutations that drive a patients breast cancer, and can successfully match patients with the best available precision medicine for their cancer.

Study co-leader Professor Judith Bliss, Professor of Clinical Trials at The Institute of Cancer Research, London, and Director of its Cancer Research UK-funded Clinical Trials and Statistics Unit, said:

The plasmaMATCH trial platform has allowed us to look at the activity of various different treatments at the same time. This efficient trial set-up has been a success and it is already starting to bring patients closer to new targeted treatments.

Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said:

Its exciting to see the first results emerging from the pioneering plasmaMATCH trial. The findings demonstrate the powerful potential of liquid biopsies to pick up mutations that although individually rare can collectively play an important role in causing many breast cancers. Crucially, the study shows that matching women to the best available precision medicine for their tumour, using a blood test rather than an invasive tissue biopsy, can have real clinical benefits.

These findings should lay the foundation for liquid biopsies to become a standard part of patient care for patients with breast cancer, and help accelerate womens access to the best available precision medicines.

Michelle Mitchell, chief executive of Cancer Research UK, said:

Our Stand Up To Cancer initiative allows us to quickly transform any promising discoveries made in the lab into new tests and treatments for people with cancer. So its absolutely fantastic that we are looking at the possibility of using a simple blood test to quickly match the best treatments for women with advanced breast cancer. Its results like these that will help us see 3 in 4 people survive their cancer by 2034.

ENDS

Notes to editors

For more information please contact Diana Cano Bordajandi in the ICR press office on 020 7153 5021 ordiana.cano@icr.ac.uk. For enquiries out of hours, please call 07595 963 613.

The plasmaMATCH trial was sponsored by the ICR and The Royal Marsden, and coordinated by the Clinical Trials and Statistics Unit at The Institute of Cancer Research (ICR-CTSU). ICR-CTSU receives core programme support from Cancer Research UK and is accredited by the UKCRC and the NCRI. Further information on the trial can be found here:https://www.icr.ac.uk/our-research/centres-and-collaborations/centres-at-the-icr/clinical-trials-and-statistics-unit/clinical-trials/plasmamatch

The Institute of Cancer Research, London,is one of the world's most influential cancer research organisations.

Scientists and clinicians at The Institute of Cancer Research (ICR) are working every day to make a real impact on cancer patients' lives. Through its unique partnership with The Royal Marsden NHS Foundation Trust and 'bench-to-bedside' approach, the ICR is able to create and deliver results in a way that other institutions cannot. Together the two organisations are rated in the top centres for cancer research and treatment globally.

The ICR has an outstanding record of achievement dating back more than 100 years. It provided the first convincing evidence that DNA damage is the basic cause of cancer, laying the foundation for the now universally accepted idea that cancer is a genetic disease. Today it is a world leader at identifying cancer-related genes and discovering new targeted drugs for personalised cancer treatment.

A college of the University of London, the ICR is the UKs top-ranked academic institution for research quality, and provides postgraduate higher education of international distinction. It has charitable status and relies on support from partner organisations, charities and the general public.

The ICR's mission is to make the discoveries that defeat cancer. For more information visithttp://www.icr.ac.uk

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Major 'plasmaMATCH' trial uses blood test to match women with breast cancer to range of precision treatments - BioSpace

When Chinese scientists posted the genetic sequence of a novel coronavirus circulating in the province of Wuhan back in January, Peter Hotez knew immediately what he needed to do.

The 62-year-old Houston infectious disease specialist dashed off an email to the National Institutes of Health, then got his Galveston and New York collaborators on a Zoom call to plot out their next step. There was no telling how far the deadly new virus might spread, but they figured they had a good lead on a possible silver bullet.

Four years ago, they had developed a vaccine that in animal models protected against the spread of severe acute respiratory syndrome (SARS), a closely related coronavirus. The vaccine never made it to human trials because the disease by then had died out, but to them it provided a blueprint for the worlds best hope against a pandemic thats now killed more than 900,000 people around the globe.

This is not going to be that difficult, Hotez, co-director of the Center for Vaccine Development at Texas Childrens Hospital, told the collaborators on Jan. 22, 11 days after the sequence was posted. We did it for SARS, and it wasnt that difficult. Im pretty sure we can do it for this virus.

Sixty miles south of the Texas Childrens center, researchers at the University of Texas Medical Branch at Galveston also think theyve got a great shot at a coronavirus vaccine.

The Galveston National Laboratory at UTMB is the nations largest high-security containment facility on an academic campus. More than 150 security cameras monitor the facility and its clear why. The lab houses many potentially dangerous substances and was the first in the U.S. with the genetic material for the coronavirus.

The UTMB researchers are working with at least 10 different vaccine candidates, some developed by pharmaceutical companies, some by the medical branch.

Scott Weaver, director of the schools infectious disease research program, notes that several vaccines will be needed to protect against the virus in all populations. Anticipating the need, UTMB scientists are developing and testing a wide range of candidates, taking advantage of innovative techniques developed in-house to determine efficacy.

The Houston-area efforts provide glimpses into the making of a vaccine for SARS-CoV-2 scientists have nicknamed it SARS2 the coronavirus that causes COVID-19, the most crippling pandemic since the 1918 Spanish Influenza. Never before has such an esoteric world, such a scientific quest, so captured a frightened worlds attention.

The efforts also showcase a frantic race that features more than 170 projects in development around the world, all aiming to be the one whose vaccine brings the virus to heel. The likely achievement, however, will come despite a historic reluctance to invest preemptively in the effort, despite frequent warnings it was only a matter of time before a pandemic hit.

Nothing is stoking expectations from the race like Operation Warp Speed, the Trump Administrations Manhattan Project-like public-private partnership to accelerate the development and distribution of vaccines for the new coronavirus. The program, still a mystery to most scientists in the field, aims to have 300 million doses of a safe and effective vaccine available for Americans by January.

If that happens, itll be the fastest vaccine development program ever in history, said Jason Schwartz, a professor of health policy and management at the Yale School of Public Health.

That timeline would ensure the Texas Childrens and UTMB efforts dont finish first both are yet to start clinical trials but it doesnt mean either cant still be judged an ultimate winner. In the long run, because latter-generation vaccines typically replace the first ones, the quest is not so much the sprint Trump promises as a marathon.

It all started with 18th century folk wisdom and a British doctor eager to connect the dots.

Like others of the time, Edward Jenner had heard the tales that milkmaids whod contracted cowpox, a mild disease that could be transferred from cattle to humans, were spared the infection of smallpox, then the worlds great scourge. Theorizing that cowpox was similar enough to confer immunity, Jenner scratched pus from a cowpox blister into the skin of an 8-year-old-boy, then six weeks later challenged the cowpox inoculation by exposing the boy to smallpox.

The boy never fell ill. A year later, having repeated the experiment on several other children, Jenner published the results and coined a new term: vaccine (derived from vacca, Latin for cow).

Jenners pioneering work led to other advances: Louis Pasteur spearheaded the development of the first successful vaccines for cholera, anthrax and rabies around the turn of the 20th century. Jonas Salk and Albert Sabin created the two polio vaccines in the 1950s.

In modern times, vaccines for smallpox, polio, yellow fever, tetanus, diphtheria, whooping cough and measles are credited with saving an estimated 9 million lives a year.

Yet almost perversely, pandemic preparedness never became an early 21st century priority. In the years before COVID-19, according to an article in the journal Nature, the United States invested less than $1 billion annually on the threat posed by emerging infectious diseases and pandemics, compared to at least $100 billion a year on counterterrorism. No more than a third of the funding went to the NIH for vaccine research.

A congressional group called the Bipartisan Commission on Biodefense led the effort to improve the nations preparedness. It had some successes, but few involved spending more on vaccine research and development. Everybody said they supported the effort, one expert noted, but nobody wanted to spend real money on it.

Had investments been made previously, we potentially could have a vaccine ready to go now, Hotez testified before the House Committee on Science, Space and Technology in March.

Hotez describes vaccines as a kind of trick on the body, preventing disease by simulating an infection, which the immune system learns to recognize and remember. The vaccine produces such simulation by exposing the subject to harmless molecules that reside on the surface of viruses and bacteria foreign enough to trigger an immune response, not dangerous enough to cause disease. Immune responses normally learned the hard way during illness caused by the infection can be induced painlessly thanks to such tricks.

Scientists historically have made molecules harmless by either killing the bug or by weakening it. Keeping the physical remains intact teaches the immune system what to look for.

The field has advanced exponentially, first the result of new techniques mass producing pieces of a virus, then the result of genetic engineering. Most recently, advances in computers abililty to quickly sequence viruses have enabled researchers to build customized snippets of the virus own genes to provoke an immune response.

The promise of the method has generated much excitement first and foremost among Operation Warp Speeds leaders even though its still experimental. No genetic vaccine has ever been licensed.

But because of the speed of the method, such genetic vaccines lead the COVID-19 vaccine candidate pack. One company says it designed a preliminary model in three hours. In late July, two started late-stage clinical trials.

Previously, the fastest a vaccine the one for the mumps has ever made it from bench to doctors office was four years. The vaccine for HPV, a sexually transmitted infection, took 15; chickenpox 28.

But researchers are optimistic about a coronavirus vaccine because the concerted effort by the scientific community seems, in the words of many, too big to fail.

The vaccine effect will take time, though. No matter how fast the creation of the new vaccine, clinical testing typically takes at least 12 months, necessary to show that it is safe and effective. The safety bar is particularly high because, unlike therapeutic drugs given to patients battling disease, vaccines are given to healthy people.

Beyond the impregnable concrete exterior of the Galveston National Laboratory, past the airport-level screening at the entrance and behind steel doors that require key code access, dozens of vials of SARS2 clones sit in a minus-80 degree freezer in a high-security biocontainment lab.

Like shes done every day for the last several months, Camila Fontes, a graduate student at the University of Texas Medical Branch, steps into a buffer room outside of the biocontainment lab to suit up in layers of personal protective equipment before handling the virus clones.

Fontes changes her shoes, puts on gloves and a blue gown, and dons an air-purifying respirator that looks like a big white hood with a glass window covering her entire face. Once she enters the lab, Fontes will put on a second pair of gloves, a second gown and shoe covers.

Thus adequately protected, Fontes retrieves one of the vials from the freezer and places it in a glass of water to thaw. She adds the cloned coronavirus to a plate containing a human blood sample immunized with a vaccine candidate, and places it in an incubator for one hour.

Afterward, Fontes will add the virus mixture to 96 dime-sized trays, each filled with 120,000 Vero cells a lineage of cloned African monkey cells suitable for propagating viruses and places those trays back in the incubator for 16 to 20 hours.

The medical branch has developed an innovative system that allows scientists to create the SARS2 strain from scratch and manipulate it. Using this technique, UTMB scientists cloned the virus and injected it with a neon green fluorescent protein.

This cloned virus will prove critical for determining whether one of the vaccine candidates under testing has strong enough antibodies to bind to the virus and block it from multiplying in human blood cells.

If the virus is effective in infecting the cells, images of the cell trays will show what looks like a paint splatter of small, day-glo neon green dots attaching to the royal blue Vero cells. If the blood sample is endowed with strong enough antibodies from the vaccine candidate, the cell tray images will show almost no green at all.

The less green we have, the better, Fontes said. That means there is protection.

For 12 hours a day in small research lab, Fontes prepares millions of the Vero cells for testing. A nine-year Army veteran, Fontes is accustomed to the disciplined, detail-oriented approach her work requires.

Im a realist, Fontes said. I have an opportunity to help everybody else. I want to see my mom and my dad. Theyre in El Paso, and if I want to see them, we need a solution.

The eight-story national laboratory on the medical branchs Galveston campus was built in 2008, funded by a $175 million grant from the National Institutes of Health. In the wake of the Sept. 11, 2001 terrorist attacks, the Bush administration sought to construct research facilities with proper precautions so-called Biosafety Level 4 lab space amid mounting concerns about emerging infectious diseases. The Galveston lab has more than 12,000 square feet of such level 4 space.

As the director of UTMBs infectious disease research programs, Scott Weaver is tasked with helping manage nearly two dozen projects behind the laboratory walls related to the coronavirus. On a summer afternoon in the Galveston lab, Weaver dons a facemask made by his wife that features a pattern of blue spike proteins that characterize the coronavirus.

He guides a reporter through the doors of one of the buildings Biosafety Level 2 labs, which Weaver describes as the workhorse of biomedical research.

All the work to prepare for the high-containment experiments and then to test samples that come out of there takes place in BSL2, he said.

Compared to the higher security labs, which require special respiratory protection and, in some cases, biohazard space suits, the level 2 labs are almost quaint: three large metal tables separated by aisles of desks piled with papers and shelves of high-tech equipment.

This lab also acts as an outpost of sorts for the universitys World Reference Center for Emerging Viruses and Arboviruses, a library of over 8,000 virus strains encompassing 21 viral families. It was here that the first SARS2 sample to reach U.S. soil was sent by the Centers for Disease Control and Prevention in February, leading to much of the primary research done on the pathogen that was then disseminated to labs across the globe.

With the genetic material of the coronavirus in-house, the Galveston lab developed a major breakthrough in vaccine testing.

Pei-Yong Shi, a professor of human genetics at UTMB, and Xuping Xie, a postdoctoral research scientist, used the initial sample to develop a new way to make the virus in the lab and manipulate it in a petri dish.

The process uses Vero cells to clone the virus. Genetic material from the virus strain is mixed with the cells and shocked with an electrical field to open up tiny holes in the cell membrane. Once the viral genetic material permeates the cell, it uses the cells machinery to create copies of the virus, effectively cloning itself.

The cloned viruss monkey DNA allows it to be easily manipulated, which led to the development of the neon green fluorescent protein that could be injected into the virus to allow for high-capacity testing of vaccines and anti-viral drugs.

The green protein is a simple concept, Shi explains, like putting on glasses to help you see better. The breakthroughs, he said, opened the door to UTMB partnering with several pharmaceutical companies to test vaccine candidates.

Maria Bottazzi was at her 87-year-old fathers home in Tegucigalpa, Honduras for the 2019 Christmas holiday, hanging out on the back porch and listening to his reminiscences about her childhood there, when the news hit about a mysterious pneumonia outbreak in China.

Bottazzi took a break from her dads stories to get on the phone with Hotez, who brought her with him to Houston in 2010 as his co-director of the Texas Childrens vaccine lab. The two agreed the outbreak resembled that of SARS, the disease that originated in China in November 2002 and spread to 29 countries. It was particularly virulent, killing 10 percent of people who contracted it before it burned out.

Both immediately thought of the centers SARS vaccine, developed earlier in the decade using a government bioterrorism preparedness grant. The grant ran out in 2016.

Is it still stable? Hotez asked. Have we been continuously validating it in tests?

All 20,000 doses manufactured by the Walter Reed Army Institute of Research remained viable in a Houston freezer, replied Bottazzi. She emailed the Texas Childrens research team in Houston, urging them to be proactive in case we need to deploy it against this mystery virus.

Bottazzi considers the period after the grant expired four years of lost time and knowledge, time during which the team could have produced human safety data and determined if the vaccine generates virus-neutralizing antibodies in people. The team applied for follow-up grants from government agencies, pharmaceutical companies and foundations, all to no avail.

It was the climate at the time. Some politicians called for more government spending on pandemic preparedness, but there were always more pressing priorities. Corrected for inflation, such funding went from over $2 billion in 2003 to a little under $1 billion in 2020.

Coronaviruses represent a departure of sorts for the TCH team, whose other work all targets neglected tropical diseases, a term coined by Hotez to describe debilitating, poverty-related syndromes largely ignored by most of medicine.

The commitment to vaccines for the worlds poorest people and his trademark neckwear have given Hotez the nickname Bono with a bow tie. He says that when he tried wearing conventional ties, the outcry was like when Dylan played electric instruments at Newport.

It didnt take long for the Hotez-Bottazzi observation about the resemblance of the SARS virus to the one in Wuhan to be confirmed. The sequence posted two weeks later showed the new virus shared 82 percent of its genes with SARS.

The team decided to proceed on parallel fronts: develop a new vaccine specific to SARS2 but also push for a clinical trial testing the SARS vaccine against the new virus, based on the seeming likelihood itd provide some cross-protection. After all, it promised help on the immediate front.

In the end, the new vaccines development took just a few months. Suddenly, the centers SARS2 vaccine has become its best candidate, set to begin clinical trials in less than a month in India.

But it remains a David among Goliaths. Operation Warp Speeds beneficiaries, seven well-heeled, for-profit companies, are each bankrolling efforts with at least $1 billion of their own funds plus more from the Trump administration, which so far has struck deals to send nearly $11 billion their way. The Texas Childrens center effort? It has $3.5 million of funding, all from philanthropy.

Still, Hotez says thats enough to advance the effort to clinical trials. Meanwhile, hes still going around, hat in hand, trying to raise money for the effort.

Its all vexing to Hotez and Bottazzi, who think their vaccine is one of the most likely to work and at a fraction of the cost. When alls said and done, suspects Hotez, therell be a role for the vaccine.

All the talk portrays this as a race, as if its going to be like Jonas Salk in 1956 again journalists assembled at the University of Michigan auditorium, curtains pulled back like the Wizard of Oz, everyone excitedly dancing off into the streets, said Hotez. Its not going to happen like that. Theres going to be a gradual roll-out of vaccines. The first ones will get replaced. Different ones will be used in different places. And no one knows how soon that will happen.

By the time it does, Hotez hopes to be focused on a more ambitious preparedness project a universal coronavirus vaccine that would protect against any future variation of the infection that might emerge, an idea the TCH lab first sought funding for a few years ago. Predictably, the NIH rejected the proposal.

todd.ackerman@chron.com

nick.powell@chron.com

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There's a frantic global race for a COVID vaccine, and Houston hopes to be an ultimate winner - Houston Chronicle

What should a precision medicine approach be in a pandemic? The gene-centric vision of precision medicine encourages people to expect individualised gene-targeted fixes

Tom Hanks and his wife, Rita Wilson, were among the earliest celebrities to catch the novel coronavirus. In an interview at the beginning of July, Hanks described how differently COVID-19 had affected each of them in March.

My wife lost her sense of taste and smell, she had severe nausea, she had a much higher fever than I did. I just had crippling body aches, he said. I was very fatigued all the time and I couldnt concentrate on anything for more than about 12 minutes.

Why does COVID-19 present such different symptoms or none at all in different people?

Preexisting conditions can only be part of the story. Hanks is over 60 and is a Type 2 diabetic, putting him in a high-risk group. Nevertheless, he survived his brush with the virus with no pneumonia and apparently without any long-lasting effects. Knowing what causes variation in different patients could help physicians tailor their treatments to individual patients an approach known as precision medicine.

In recent years, a gene-centric approach to precision medicine has been promoted as the future of medicine. It underlies the massive effort funded by the US National Institutes of Health to collect over a million DNA samples under the All of Us initiative that began in 2015.

But the imagined future did not include COVID-19. In the rush to find a COVID-19 vaccine and effective therapies, precision medicine has been insignificant. Why is this? And what are its potential contributions?

We are a physician geneticist and a philosopher of science who began a discussion about the promise and potential pitfalls of precision medicine before the arrival of COVID-19. If precision medicine is the future of medicine, then its application to pandemics generally, and COVID-19 in particular, may yet prove to be highly significant. But its role so far has been limited. Precision medicine must consider more than just genetics. It requires an integrative omic approach that must collect information from multiple sources beyond just genes and at scales ranging from molecules to society.

From genetics to microbes

Inherited diseases such as sickle cell anemia and Tay-Sachs disease follow a predictable pattern. But such direct genetic causes are perhaps the exception rather than the rule when it comes to health outcomes. Some heritable conditions for instance, psoriasis or the many forms of cancer depend on complex combinations of genes, environmental and social factors whose individual contributions to the disease are difficult to isolate. At best, the presence of certain genes constitutes a risk factor in a population but does not fully determine the outcome for an individual person carrying those genes.

The situation becomes yet more complicated for infectious diseases.

Viruses and bacteria have their own genomes that interact in complex ways with the cells in the people they infect. The genome of SARS-CoV-2 underlying COVID-19 has been extensively sequenced. Its mutations are identified and traced worldwide, helping epidemiologists understand the spread of the virus. However, the interactions between SARS-CoV-2 RNA and human DNA, and the effect on people of the viruss mutations, remain unknown.

The importance of multi-scale data

Tom Hanks and his wife caught the virus and recovered in a matter of weeks. Presumably each was infected over the course of a few minutes of exposure to another infected person, involving cellular mechanisms that operate on a timescale of milliseconds.

But the drama of their illness, and that of the many victims with far worse outcomes, is taking place in the context of a global pandemic that has already lasted months and may continue for years. People will need to adopt changes in their behavior for weeks or months at a time.

What should a precision medicine approach be in a pandemic? The gene-centric vision of precision medicine encourages people to expect individualised gene-targeted fixes. But, genes, behavior and social groups interact over multiple timescales.

To capture all the data needed for such an approach is beyond possibility in the current crisis. A nuanced approach to the COVID-19 pandemic will depend heavily on imprecise population level public health interventions: mask-wearing, social distancing and working from home. Nevertheless, there is an opportunity to begin gathering the kinds of data that would allow for a more comprehensive precision medicine approach one that is fully aware of the complex interactions between genomes and social behavior.

How to use precision medicine to understand COVID-19

With unlimited resources, a precision medicine approach would begin by analyzing the genomes of a large group of people already known to be exposed to SARS-CoV-2 yet asymptomatic, along with a similar-sized group with identified risk factors who are dying from the disease or are severely ill.

An early study of this kind by Precisionlife Ltd data mined genetic samples of 976 known COVID-19 cases. Of these, 68 high-risk genes were identified as risk factors for poor COVID-19 outcomes, with 17 of them deemed likely to be good targets for drug developments. But, as with all such statistical approaches, the full spectrum of causes underlying their association with the disease is not something the analysis provides. Other studies of this kind are appearing with increasing frequency, but there is no certainty in such fast-moving areas of science. Disentangling all the relevant factors is a process that will take months to years.

To date, precision medicine has proven better suited to inherited diseases and to diseases such as cancer, involving mutations acquired during a persons lifetime, than to infectious diseases. There are examples where susceptibility to infection can be caused by malfunction of unique genes such as the family of inherited immune disorders known as agammaglobulinemia, but these are few and far between.

Many physicians assume that most diseases involve multiple genes and are thus not amenable to a precision approach. In the absence of the kind of information needed for a multi-omic approach, there is a clear challenge and opportunity for precision medicine here: If it is to be the future of medicine, in order to complement and expand our existing knowledge and approaches, it needs to shift from its gene-centric origins toward a broader view that includes variables like proteins and metabolites. It must consider the relationships between genes and their physical manifestations on scales that range from days to decades, and from molecules to the global society.

Colin Allen, Distinguished Professor of History & Philosophy of Science, University of Pittsburgh and David Finegold, Professor, Department of Human Genetics, Pitt Public Health, University of Pittsburgh

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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How to use precision medicine to personalise COVID-19 treatment according to the patient's genes - Down To Earth Magazine

Researchers at Weill Cornell Medicine-Qatar (WCM-Q) have unveiled the key role played by a specific protein in the growth of the most aggressive, treatment-resistant forms of breast cancer.

A multi-institutional international study led by WCM-Qs Dr. Lotfi Chouchane, Professor of Genetic Medicine, Microbiology and Immunology, found that the effects of a protein named STXBP6 are profoundly suppressed in triple-negative breast cancers (TNBCs), which are known to relapse early and tend to spread to other organs despite intensive treatments with surgery, chemotherapy and radiotherapy.

TNBCs account for around 15-20 percent of all breast cancers and are associated with the poorest patient outcomes. While many other forms of breast cancer can now be treated relatively successfully, there is currently no effective therapy that specifically targets TNBCs.

The study showed that the STXBP6 protein helps regulate and promote a natural cellular process called autophagy in which old and damaged cells are metabolized or killed off in order to allow newer, healthier ones to grow. In cancer cells, autophagy suppresses tumor growth by inhibiting cancer cell survival and inducing cell death. When autophagy is suppressed in certain circumstances, cancer cells are more able to grow and proliferate.

Dr. Chouchane said: There is a real need to develop new therapies that specifically target triple-negative breast cancers because they do not respond well to existing treatments. In this study, we were able to significantly enhance our understanding of the mechanisms that make TNBCs so aggressive and treatment-resistant, which we hope will provide targets for the development of effective new therapies for TNBCs to significantly improve patient outcomes.

Triple-negative breast cancers are so called because the cancer cells do not have estrogen or progesterone receptors (which are targets for hormone-based therapies) and because they do not make a protein called HER2 (which is a target for antibody-based therapies) like some other forms of breast cancer.

The study, titled STXBP6, reciprocally regulated with autophagy, reduces triple negative breast cancer aggressiveness, also involved researchers at Weill Cornell Medicine in New York, Sidra Medicine and Hamad Medical Corporation in Doha, and the University of Groningen in the Netherlands. The research has been published inClinical and Translational Medicine, a prestigious medical journal.

Dr. Chouchane explained that laboratory analysis showed the STXBP6 protein interacting with another protein, named SNX27, which is known to play a key role in autophagy. Furthermore, the researchers found that increased function of the STXBP6 protein significantly reduced TNBC cells migratory ability in cell-based in vitro experiments and also reduced tumor metastasis in mouse model-based in vivo testing. However, while autophagy appears to be heavily involved in maintaining cellular health and preventing tumor initiation, the process has a paradoxical dual role and in other circumstances can actually facilitate tumor survival, depending on a variety of factors such as cancer type and stage.

Dr. Chouchane added: This multi-institutional study represents a new paradigm in our understanding of the role of autophagy in breast cancers, but it is an extremely complex and multifaceted process. We believe much more research is needed to understand in detail the role of autophagy throughout the many different development stages of cancer in order to create a new class of therapeutic strategies that are truly effective and safe.

The study was supported by funding from the Biomedical Research Program of WCM-Q and by a grant from the Qatar National Research Fund (NPRP9-459-3-090).

Dr. Khaled Machaca, WCM-Q Professor of Physiology and Biophysics/Senior Associate Dean for Research, Innovations, and Commercialization, said: This cutting-edge research paves the way for further investigations into the cellular processes that allow triple-negative breast cancers to resist current therapeutic strategies. Furthermore, the study provides extremely useful targets to aid the design of new, more effective cancer drugs in the future. These are very positive developments toward applying our research findings to improve healthcare delivery in Qatar in the long term.

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WCM-Q Research Reveals Underlying Mechanisms of Aggressive Breast Cancers - Al-Bawaba

GAITHERSBURG, Md., Sept. 02, 2020 (GLOBE NEWSWIRE) -- Novavax, Inc. (Nasdaq: NVAX), a late stage biotechnology company developing next-generation vaccines for serious infectious diseases, today announced the publication in The New England Journal of Medicine of Phase 1 data from its Phase 1/2 clinical trial of NVXCoV2373, its COVID19 vaccine candidate adjuvanted with MatrixM, in healthy adults 18-59 years of age. The publication offers further detail on the previously announced results, in which NVXCoV2373 demonstrated a reassuring safety and reactogenicity profile and induced robust antibody responses numerically superior to that seen in human convalescent sera. The manuscript is available at https://www.nejm.org/doi/full/10.1056/NEJMoa2026920?query=featured_coronavirus.

The rapid publication of Phase 1 results from our trial in a prestigious peer-reviewed journal reflects both the importance of the data and the urgent need for an effective vaccine to slow the COVID-19 pandemic, said Gregory M. Glenn, M.D., President of Research and Development at Novavax. Based on the positive Phase 1 results, we have begun multiple Phase 2 clinical trials, from which we expect to collect preliminary efficacy. Novavax is committed to generating the safety, immunogenicity and efficacy data that will support confident usage of the vaccine, both in the US and globally, and the data published today further bolsters our conviction that this is possible.

The Phase 1 portion of the Phase 1/2 clinical trial was randomized, observer-blinded, and placebo-controlled.

NVX-CoV2373 is currently in multiple Phase 2 clinical trials. The Phase 2 portion of the Phase 1/2 clinical trial to evaluate the safety and immunogenicity of NVX-CoV2373 began in August inthe United StatesandAustralia, and expands on the age range of the Phase 1 portion by including older adults 60-84 years of age as approximately 50 percent of the trial population. Secondary objectives include preliminary evaluation of efficacy. In addition, a Phase 2b clinical trial to assess efficacy began inSouth Africain August.

The trial was supported by funding from the Coalition for Epidemic Preparedness Innovations (CEPI) and was conducted at two sites in Australia.

Phase 1 Results Summary

Further details may be found in Novavax August 4 announcement of Phase 1 results and may be accessed here.

About NVX-CoV2373

NVXCoV2373 is a vaccine candidate engineered from the genetic sequence of SARSCoV2, the virus that causes COVID-19 disease. NVXCoV2373 was created using Novavax recombinant nanoparticle technology to generate antigen derived from the coronavirus spike (S) protein and contains Novavax patented saponin-based Matrix-M adjuvant to enhance the immune response and stimulate high levels of neutralizing antibodies. In preclinical trials, NVXCoV2373 demonstrated indication of antibodies that block binding of spike protein to receptors targeted by the virus, a critical aspect for effective vaccine protection. In its Phase 1 portion of the Phase 1/2 clinical trial, NVXCoV2373 was generally well-tolerated and elicited robust antibody responses numerically superior to that seen in human convalescent sera. Phase 2 clinical trials began in August 2020. Novavax has secured $2 billion in funding for its global coronavirus vaccine program, including up to $388 million in funding from the Coalition for Epidemic Preparedness Innovations (CEPI).

About Matrix-M

Novavax patented saponin-based Matrix-M adjuvant has demonstrated a potent and well-tolerated effect by stimulating the entry of antigen-presenting cells into the injection site and enhancing antigen presentation in local lymph nodes, boosting immune response.

About Novavax

Novavax, Inc. (Nasdaq:NVAX) is a late-stage biotechnology company that promotes improved health globally through the discovery, development, and commercialization of innovative vaccines to prevent serious infectious diseases. Novavax is undergoing clinical trials for NVX-CoV2373, its vaccine candidate against SARS-CoV-2, the virus that causes COVID-19. NanoFlu, its quadrivalent influenza nanoparticle vaccine, met all primary objectives in its pivotal Phase 3 clinical trial in older adults. Both vaccine candidates incorporate Novavax proprietary saponin-based Matrix-M adjuvant in order to enhance the immune response and stimulate high levels of neutralizing antibodies. Novavax is a leading innovator of recombinant vaccines; its proprietary recombinant technology platform combines the power and speed of genetic engineering to efficiently produce highly immunogenic nanoparticles in order to address urgent global health needs.

For more information, visit http://www.novavax.com and connect with us on Twitter and LinkedIn.

Novavax Forward-Looking Statements

Statements herein relating to the future of Novavax and the ongoing development of its vaccine and adjuvant products are forward-looking statements. Novavax cautions that these forward-looking statements are subject to numerous risks and uncertainties, which could cause actual results to differ materially from those expressed or implied by such statements. These risks and uncertainties include those identified under the heading Risk Factors in the Novavax Annual Report on Form 10-K for the year ended December 31, 2019, and Quarterly Report on Form 8-K for the period ended June 30, 2020, as filed with the Securities and Exchange Commission (SEC). We caution investors not to place considerable reliance on forward-looking statements contained in this press release. You are encouraged to read our filings with the SEC, available at sec.gov, for a discussion of these and other risks and uncertainties. The forward-looking statements in this press release speak only as of the date of this document, and we undertake no obligation to update or revise any of the statements. Our business is subject to substantial risks and uncertainties, including those referenced above. Investors, potential investors, and others should give careful consideration to these risks and uncertainties.

Contacts:

Novavax

InvestorsSilvia Taylor and Erika Trahanir@novavax.com240-268-2022

MediaBrandzone/KOGS CommunicationEdna Kaplankaplan@kogspr.com617-974-8659

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Novavax Announces Publication of Phase 1 Data for COVID-19 Vaccine Candidate in The New England Journal of Medicine - GlobeNewswire

1. Environmental liability for schizophrenia moderated the association of stressful life events with mental and physical health.

Evidence Rating Level: 2 (Good)

Schizophrenia research has elucidated the roles of environmental and genetic liability as well as stressful life events (SLEs) in schizophrenia pathogenesis. However, few studies have illustrated the interactions of these risk factors and how they impact mental and physical health. This population-based prospective cohort study investigated the prevalence, incidence, course, and consequences of psychiatric disorders in the Netherlands. A total of 6,646 (M [SD] age = 44.26 [12.54] years, 55.25% female) participants were enrolled between November 5, 2007 and July 31, 2009, being followed up with by three assessments across nine years. Follow-ups included recent SLEs and aggregate scores of environmental and genetic liabilities (polygenic risk score for schizophrenia [PRS-SCZ]; exposome score for schizophrenia [ES-SCZ]). SLEs were significantly associated with reduced mental (B = -3.68, 95% CI -4.05 to -3.32) and physical health (B = -3.22, 95% CI -3.66 to -2.79). Genetic and environmental liabilities were associated with poorer mental health (PRS-SCZ: B = -0.93, 95% CI -1.31 to -0.54; ES-SCZ: B = -3.07, 95% CI -3.35 to -2.79), with environmental liability also being associated with reduced physical health (B = -3.19, 95% CI -3.56 to -2.82). The interaction model suggested that ES-SCZ moderated the association of SLEs with physical (B = -0.64, 95% CI -1.11 to -0.17) and mental health (B = -1.08, 95% CI -1.47 to -0.69). PRS-SCZ, however, did not moderate this relationship. Overall, both genetic and environmental liabilities for schizophrenia resulted in mental health outcomes across the population. Exposure to SLEs, specifically in the context of these liabilities, were further associated with poorer health outcomes. Thus, it is important to consider the environmental factors impacting schizophrenia, such that modifiable risk factors should be targets of prevention and ongoing treatment.

Click to read the study in JAMA Psychiatry

Image: PD

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Tom Hanks and his wife, Rita Wilson, were among the earliest celebrities to catch the novel coronavirus. In an interview at the beginning of July, Hanks described how differently COVID-19 had affected each of them in March.

My wife lost her sense of taste and smell, she had severe nausea, she had a much higher fever than I did. I just had crippling body aches, he said. I was very fatigued all the time and I couldnt concentrate on anything for more than about 12 minutes.

Why does COVID-19 present such different symptoms or none at all in different people?

Preexisting conditions can only be part of the story. Hanks is over 60 and is a Type 2 diabetic, putting him in a high-risk group. Nevertheless, he survived his brush with the virus with no pneumonia and apparently without any long-lasting effects. Knowing what causes variation in different patients could help physicians tailor their treatments to individual patients an approach known as precision medicine.

In recent years, a gene-centric approach to precision medicine has been promoted as the future of medicine. It underlies the massive effort funded by the U.S. National Institutes of Health to collect over a million DNA samples under the All of Us initiative that began in 2015.

But the imagined future did not include COVID-19. In the rush to find a COVID-19 vaccine and effective therapies, precision medicine has been insignificant. Why is this? And what are its potential contributions?

We are a physician geneticist and a philosopher of science who began a discussion about the promise and potential pitfalls of precision medicine before the arrival of COVID-19. If precision medicine is the future of medicine, then its application to pandemics generally, and COVID-19 in particular, may yet prove to be highly significant. But its role so far has been limited. Precision medicine must consider more than just genetics. It requires an integrative omic approach that must collect information from multiple sources beyond just genes and at scales ranging from molecules to society.

Inherited diseases such as sickle cell anemia and Tay-Sachs disease follow a predictable pattern. But such direct genetic causes are perhaps the exception rather than the rule when it comes to health outcomes. Some heritable conditions for instance, psoriasis or the many forms of cancer depend on complex combinations of genes, environmental and social factors whose individual contributions to the disease are difficult to isolate. At best, the presence of certain genes constitutes a risk factor in a population but does not fully determine the outcome for an individual person carrying those genes.

The situation becomes yet more complicated for infectious diseases.

Viruses and bacteria have their own genomes that interact in complex ways with the cells in the people they infect. The genome of SARS-CoV-2 underlying COVID-19 has been extensively sequenced. Its mutations are identified and traced worldwide, helping epidemiologists understand the spread of the virus. However, the interactions between SARS-CoV-2 RNA and human DNA, and the effect on people of the viruss mutations, remain unknown.

Tom Hanks and his wife caught the virus and recovered in a matter of weeks. Presumably each was infected over the course of a few minutes of exposure to another infected person, involving cellular mechanisms that operate on a timescale of milliseconds.

But the drama of their illness, and that of the many victims with far worse outcomes, is taking place in the context of a global pandemic that has already lasted months and may continue for years. People will need to adopt changes in their behavior for weeks or months at a time.

What should a precision medicine approach be in a pandemic? The gene-centric vision of precision medicine encourages people to expect individualized gene-targeted fixes. But, genes, behavior and social groups interact over multiple timescales.

To capture all the data needed for such an approach is beyond possibility in the current crisis. A nuanced approach to the COVID-19 pandemic will depend heavily on imprecise population level public health interventions: mask-wearing, social distancing and working from home. Nevertheless, there is an opportunity to begin gathering the kinds of data that would allow for a more comprehensive precision medicine approach one that is fully aware of the complex interactions between genomes and social behavior.

With unlimited resources, a precision medicine approach would begin by analyzing the genomes of a large group of people already known to be exposed to SARS-CoV-2 yet asymptomatic, along with a similar-sized group with identified risk factors who are dying from the disease or are severely ill.

An early study of this kind by Precisionlife Ltd data mined genetic samples of 976 known COVID-19 cases. Of these, 68 high-risk genes were identified as risk factors for poor COVID-19 outcomes, with 17 of them deemed likely to be good targets for drug developments. But, as with all such statistical approaches, the full spectrum of causes underlying their association with the disease is not something the analysis provides. Other studies of this kind are appearing with increasing frequency, but there is no certainty in such fast-moving areas of science. Disentangling all the relevant factors is a process that will take months to years.

To date, precision medicine has proven better suited to inherited diseases and to diseases such as cancer, involving mutations acquired during a persons lifetime, than to infectious diseases. There are examples where susceptibility to infection can be caused by malfunction of unique genes such as the family of inherited immune disorders known as agammaglobulinemia, but these are few and far between.

Many physicians assume that most diseases involve multiple genes and are thus not amenable to a precision approach. In the absence of the kind of information needed for a multi-omic approach, there is a clear challenge and opportunity for precision medicine here: If it is to be the future of medicine, in order to complement and expand our existing knowledge and approaches, it needs to shift from its gene-centric origins toward a broader view that includes variables like proteins and metabolites. It must consider the relationships between genes and their physical manifestations on scales that range from days to decades, and from molecules to the global society.

Read more:
How to use precision medicine to personalize COVID-19 treatment according to the patient's genes - The Conversation US