Monthly Archives: March 2021

Visit the News Hub

Researchers seek participants with diabetes that doesnt fit type 1 or type 2 categories

Most diabetes patients have either type 1, which is managed with insulin injections, or type 2, treated with other medications. Researchers at Washington University School of Medicine in St. Louis are part of a national research network aiming to discover rare forms of diabetes as a first step toward providing more effective treatments for forms of the disorder that don't fit neatly into either type 1 or type 2.

Washington University School of Medicine in St. Louis is part of a national research network aiming to discover rare forms of diabetes as a first step toward providing more effective treatments.

Most patients diagnosed with diabetes have either type 1, which is managed with insulin injections because patients cant make their own insulin, or type 2, in which patients either dont make enough insulin or dont respond well to the insulin their bodies produce. People with type 2 diabetes are treated with medications.

But an increasing number of patients dont fall into these two general categories, and they need a more precise diagnosis and a more individualized treatment. The Rare and Atypical Diabetes Network (RADIANT), funded by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (NIH) will involve about 2,000 people nationwide who will be screened for unusual forms of diabetes.

We are looking for new and different forms of diabetes, particularly in immigrant and minority populations, where it has been reported that atypical forms of diabetes are more common, said Fumihiko Urano, MD, PhD, the lead investigator at the Washington University clinical site. We also are looking for rare types of diabetes that result from specific gene mutations. Using precision medicine, we have tools now to identify, and possibly to treat more effectively, these rare forms of disease.

Urano, the Samuel E. Schechter Professor of Medicine and a professor of pathology and immunology, plans to recruit 200 patients with diabetes in the next year at the Washington University site. He and the other network researchers envision building a comprehensive database of genetic, clinical and descriptive data about previously unidentified forms of diabetes to provide more information about those forms of the illness to doctors and researchers, allowing them to recognize atypical forms of diabetes more quickly, as well as to develop new or more personalized treatment strategies.

Those eligible to participate include individuals diagnosed with type 2 diabetes before the onset of puberty, those with type 2 diabetes who are not overweight, and people with a family history of diabetes, particularly those from families where most family members with diabetes were diagnosed before the age of 18. Investigators also are seeking those with very abnormal cholesterol or lipid levels and an unusual distribution of body fat, as well as people whose diabetes appears to wax and wane. Those not eligible for the study include people who have a high likelihood of having an already known form of diabetes and women who are pregnant.

Study subjects will be asked to complete surveys and to provide measurements of height, weight and blood pressure. They also will undergo genetic testing and be asked to provide researchers with detailed family histories.

Next, experts will review surveys and test results to determine whether an individuals diabetes can be considered atypical or rare.

Most people with atypical diabetes are diagnosed, at least initially, with type 1 or type 2 diabetes, but they tend to experience a different disease course, different complications or unusual responses to standard diabetes medications.

Urano has experience treating an extremely rare and atypical form of diabetes known as Wolfram Syndrome. That disorder features blood sugar problems, but unlike more common forms of diabetes, it is caused by a single genetic mutation and progresses to include serious vision, balance and other neurological problems.

As part of the RADIANT study, researchers will select certain participants to gather detailed clinical and biological information through a wide range of tests, including genome sequencing, blood sampling and physical exams; and participants may get additional specialized tests based on the specific characteristics of their form of diabetes.

Family members of enrolled participants also may be invited to participate in the study, particularly if the condition appears to be inherited. Members of minority groups are particularly encouraged to apply for the study because different forms of atypical diabetes although rare tend to be more common in minority populations than in Caucasians.

Its extremely frustrating for people with atypical diabetes when their diabetes seems so different and difficult to manage, said the studys project scientist, Christine Lee, MD, of the NIHs National Institute of Diabetes and Digestive and Kidney Diseases. Through RADIANT, we want to help patients and the broader health-care community by finding and studying new types of diabetes to shed light on how and why diabetes can vary so greatly.

Urano added, Our goal is to further clarify diabetes in its many different forms. By focusing on rare forms of diabetes, the study should help us better understand the spectrum of diabetes to improve the lives of people who have these rare forms of diabetes, and to assist the people who care for them.

Nationwide, the study is being led by researchers at the University of South Florida, the Baylor College of Medicine in Houston, and the University of Chicago.

For more information, people who have forms of diabetes that seem different from common types of the disorder may call Stacy Hurst at 314-747-3294, e-mail AtypicalDiabetes@wustl.edu or visit http://www.atypicaldiabetesnetwork.org for more information about the study and how to join.

This study is supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (NIH). Grant numbers U54 DK118638 and U54 DK118612.

Washington University School of Medicines 1,500 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is a leader in medical research, teaching and patient care, ranking among the top 10 medical schools in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

Read this article:
Major NIH study seeks to understand unusual forms of diabetes Washington University School of Medicine in St. Louis - Washington University School of...

BOSTON and LONDON, March 02, 2021 (GLOBE NEWSWIRE) -- Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader, today reported financial results for the year ended December 31, 2020, as well as recent accomplishments, 2021 strategic priorities and upcoming milestones, and related organizational leadership updates.

Frank Thomas, president and chief operating officer said, It is gratifying to witness the positive momentum Orchard has already established in early 2021 driven by solid execution. Our compelling data in neurodegenerative disorders at the WORLDSymposium and successful completion of the $150 million financing exemplify this recent progress and showcase a growing appreciation for the potential of HSC gene therapy. We look forward to continuing our work in the year ahead and delivering further benefit for patients and our shareholders."

Recent Accomplishments

February 2021

January 2021

2021 Corporate Priorities and Upcoming Milestones

Orchard previously outlined the following key corporate objectives and upcoming expected milestones:

Organizational Leadership Updates

Given the progress on key development programs, Anne Dupraz has been appointed to the expanded role of chief development officer. In addition to overseeing the companys regulatory strategy, Ms. Dupraz will lead product development with the goal of ensuring a seamless approach to moving Orchards programs through to potential regulatory approval. Ms. Dupraz possesses more than 20 years of experience in the clinical and regulatory fields and has deep expertise in advanced therapies, having been involved in more than 50 different tissue, cell and gene-based therapy development programs in her career.

Ran Zheng, chief technical officer, and Andrea Spezzi, chief medical officer, are stepping down from their respective leadership positions with Orchard to pursue other opportunities. Orchard has initiated a global search for permanent replacements for both of these roles.

Fourth Quarter 2020 Financial Results

Research and development expenses were $22.6 million for the three months ended December 31, 2020, compared to $30.9 million in the same period in 2019. R&D expenses include the costs of clinical trials and preclinical work on the companys portfolio of investigational gene therapies, as well as costs related to regulatory, manufacturing, license fees and milestone payments under the companys agreements with third parties, and personnel costs to support these activities. The company expects R&D expenses to grow slightly in the upcoming periods as the company continues to advance its programs through later stages of development.

Selling, general and administrative expenses were $16.2 million for the three months ended December 31, 2020, compared to $18.5 million in the same period in 2019. The decrease was primarily due to realization of savings associated with an updated strategy and corporate restructuring announced in May 2020.

Net loss attributable to ordinary shareholders was $33.6 million for the three months ended December 31, 2020, compared to $45.4 million in the same period in 2019. The decline in net loss as compared to the prior year was primarily due to savings realized in our operating expenses as a result of the companys updated strategy and corporate restructuring. The company had 98.3 million ordinary shares outstanding as of December 31, 2020.

Thomas continued, "Our burn rate has declined from prior periods as we see the positive impact of our May 2020 corporate restructuring take hold, providing a longer runway and greater financial flexibility, aided by our recent financing. We are investing to support execution for the highest value programs in our portfolio while also dedicating capital to our longer-term strategy to expand into larger indications.

Cash, cash equivalents and investments as of December 31, 2020, were $191.9 million compared to $325.0 million as of December 31, 2019, with the decrease primarily driven by cash used to fund operations in 2020. In the fourth quarter of 2020, the cash used to fund operations was approximately $12.0 million after the receipt of approximately $19.2 million from R&D tax credit refunds related to 2019 qualifying activities under the tax code in the UK. The company expects that its cash, cash equivalents and investments as of December 31, 2020, along with gross proceeds of $150.0 million from the February 2021 private placement, will support its currently anticipated operating expenses and capital expenditure requirements into the first half of 2023. This cash runway excludes the $50 million available under the companys credit facility and any non-dilutive capital received from potential future partnerships or priority review vouchers granted by the FDA following future potential U.S. approvals.

About Libmeldy / OTL-200

Libmeldy (autologous CD34+ cell enriched population that contains hematopoietic stem and progenitor cells (HSPC) transduced ex vivo using a lentiviral vector encoding the human arylsulfatase-A (ARSA) gene), also known as OTL-200, has been approved by the European Commission for the treatment of MLD in eligible early-onset patients characterized by biallelic mutations in the ARSA gene leading to a reduction of the ARSA enzymatic activity in children with i) late infantile or early juvenile forms, without clinical manifestations of the disease, or ii) the early juvenile form, with early clinical manifestations of the disease, who still have the ability to walk independently and before the onset of cognitive decline. Libmeldy is the first therapy approved for eligible patients with early-onset MLD.

The most common adverse reaction attributed to treatment with Libmeldy was the occurrence of anti-ARSA antibodies. In addition to the risks associated with the gene therapy, treatment with Libmeldy is preceded by other medical interventions, namely bone marrow harvest or peripheral blood mobilization and apheresis, followed by myeloablative conditioning, which carry their own risks. During the clinical studies, the safety profiles of these interventions were consistent with their known safety and tolerability.

For more information about Libmeldy, please see the Summary of Product Characteristics (SmPC) available on the EMA website.

Libmeldy is not approved outside of the European Union, UK, Iceland, Liechtenstein and Norway. OTL-200 is an investigational therapy in the US.

Libmeldy was developed in partnership with the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in Milan, Italy.

About Orchard

Orchard Therapeutics is a global gene therapy leader dedicated to transforming the lives of people affected by rare diseases through the development of innovative, potentially curative gene therapies. Our ex vivo autologous gene therapy approach harnesses the power of genetically modified blood stem cells and seeks to correct the underlying cause of disease in a single administration. In 2018, Orchard acquired GSKs rare disease gene therapy portfolio, which originated from a pioneering collaboration between GSK and the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy. Orchard now has one of the deepest and most advanced gene therapy product candidate pipelines in the industry spanning multiple therapeutic areas where the disease burden on children, families and caregivers is immense and current treatment options are limited or do not exist.

Orchard has its global headquarters in London and U.S. headquarters in Boston. For more information, please visit http://www.orchard-tx.com, and follow us on Twitter and LinkedIn.

Availability of Other Information About Orchard

Investors and others should note that Orchard communicates with its investors and the public using the company website (www.orchard-tx.com), the investor relations website (ir.orchard-tx.com), and on social media (Twitter and LinkedIn), including but not limited to investor presentations and investor fact sheets, U.S. Securities and Exchange Commission filings, press releases, public conference calls and webcasts. The information that Orchard posts on these channels and websites could be deemed to be material information. As a result, Orchard encourages investors, the media, and others interested in Orchard to review the information that is posted on these channels, including the investor relations website, on a regular basis. This list of channels may be updated from time to time on Orchards investor relations website and may include additional social media channels. The contents of Orchards website or these channels, or any other website that may be accessed from its website or these channels, shall not be deemed incorporated by reference in any filing under the Securities Act of 1933.

Forward-Looking Statements

This press release contains certain forward-looking statements about Orchards strategy, future plans and prospects, which are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include express or implied statements relating to, among other things, Orchards business strategy and goals, including its plans and expectations for the commercialization of Libmeldy, the therapeutic potential of Libmeldy (OTL-200) and Orchards product candidates, including the product candidates referred to in this release, Orchards expectations regarding its ongoing preclinical and clinical trials, including the timing of enrollment for clinical trials and release of additional preclinical and clinical data, the likelihood that data from clinical trials will be positive and support further clinical development and regulatory approval of Orchard's product candidates, and Orchards financial condition and cash runway into the first half of 2023. These statements are neither promises nor guarantees and are subject to a variety of risks and uncertainties, many of which are beyond Orchards control, which could cause actual results to differ materially from those contemplated in these forward-looking statements. In particular, these risks and uncertainties include, without limitation: the risk that prior results, such as signals of safety, activity or durability of effect, observed from clinical trials of Libmeldy will not continue or be repeated in our ongoing or planned clinical trials of Libmeldy, will be insufficient to support regulatory submissions or marketing approval in the US or to maintain marketing approval in the EU, or that long-term adverse safety findings may be discovered; the risk that any one or more of Orchards product candidates, including the product candidates referred to in this release, will not be approved, successfully developed or commercialized; the risk of cessation or delay of any of Orchards ongoing or planned clinical trials; the risk that Orchard may not successfully recruit or enroll a sufficient number of patients for its clinical trials; the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical studies or clinical trials will not be replicated or will not continue in ongoing or future studies or trials involving Orchards product candidates; the delay of any of Orchards regulatory submissions; the failure to obtain marketing approval from the applicable regulatory authorities for any of Orchards product candidates or the receipt of restricted marketing approvals; the inability or risk of delays in Orchards ability to commercialize its product candidates, if approved, or Libmeldy, including the risk that Orchard may not secure adequate pricing or reimbursement to support continued development or commercialization of Libmeldy; the risk that the market opportunity for Libmeldy, or any of Orchards product candidates, may be lower than estimated; and the severity of the impact of the COVID-19 pandemic on Orchards business, including on clinical development, its supply chain and commercial programs. Given these uncertainties, the reader is advised not to place any undue reliance on such forward-looking statements.

Other risks and uncertainties faced by Orchard include those identified under the heading "Risk Factors" in Orchards quarterly report on Form 10-Q for the quarter ended September 30, 2020, as filed with the U.S. Securities and Exchange Commission (SEC), as well as subsequent filings and reports filed with the SEC. The forward-looking statements contained in this press release reflect Orchards views as of the date hereof, and Orchard does not assume and specifically disclaims any obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required by law.

Contacts

InvestorsRenee LeckDirector, Investor Relations+1 862-242-0764Renee.Leck@orchard-tx.com

MediaChristine HarrisonVice President, Corporate Affairs+1 202-415-0137media@orchard-tx.com

Go here to read the rest:
Orchard Therapeutics Reports 2020 Financial Results and Reviews Recent Accomplishments - BioSpace

In the months after Carson Miller was born, his parents Danny and Nikkia young couple living in Northern Californianoticed that he was having trouble with basic movements, like rolling over and crawling. He managed to take a few steps at 12 months but never got beyond that. When his brother Chase was born a year later, the parents anxiety turned to dismay as the younger boy also struggled with motor activity. Desperate to understand what was wrong, Danny and Nikki took their wheelchair-bound children to a series of doctors, enduring test after test; yet a diagnosis remained elusive. Finally, the family saw a group of medical detectivespart of an academic consortium called the Undiagnosed Diseases Networkwho subjected the familys DNA to a comprehensive analysis. The doctors at last identified the problem: an unusual defect in the energy machinery of the boys cells. Diagnosis firmly in hand, the family could now turn their attention to treatment.

The fact that critical information lurks within the three billion or so pairs of letters representing our genetic instructions was a key driver of the Human Genome Project, begun in 1990 and completed, with suitable fanfare, 13 years later. But translating DNA sequence into actionable insight hasnt been easy. This is a major theme of The Genome Odyssey, Euan Ashleys impassioned, firsthand account of the effort to bring genomic data into clinical practice and help patients like Carson and Chase.

For starters, says Dr. Ashley, a cardiologist and geneticist at Stanford, there was the priceprohibitively high early on. Thanks to advances in technology, the cost of sequencing an individuals DNA has declined a million-fold since 2003the equivalent, he says, of a Ferrari plummeting from $350,000 to less than 40 cents. The time required to decode a genome has plunged to days rather than years or months. When Jazlene, a newborn girl with a dangerously abnormal heart rhythm, arrived at Stanford in 2014, Dr. Ashley and his colleagues were able to identify the genetic cause within days and practice more precise medicine by fine-tuning the infants therapy.

At the level of DNA, humans are 99.9% identical, Dr. Ashley reminds us. The challenge, for doctors, lies in figuring out which differences in the remaining 0.1% are medically pertinent. For many families, the diagnosis of a rare genetic disease marks the end of one journey and the beginning of a second one, focused on learning from similar patients and partnering with researchers to search for a cure.

While Dr. Ashley concentrates on genetic disease, he also highlights the promise of DNA superhumanspeople who have been dealt an unusually good genetic hand. One example: Sharlayne Tracy, a college student in Dallas who enrolled in a University of Texas Southwestern study of cardiovascular health and was found to have astonishingly low levels of bad cholesterol. DNA analysis revealed a genetic defect disrupting PCSK9, a protein involved in cholesterol metabolism. The discovery prompted several pharmaceutical companies to develop medications targeting this protein. Two of the drugs, for the treatment of stubbornly high cholesterol, have been approved by the FDA.

Read the rest here:
The Genome Odyssey Review: From Code to Clinic - The Wall Street Journal

Tony Ho, Head of Research and Development at CRISPR Therapeutics, offers his insights into the advantages of CRISPR gene editing over other technologies and what the future holds for the genome editing field.

For decades, gene editing required engineering DNA-cutting enzymes, such as zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), for every specific genetic modification. The advent of CRISPR-Cas9, a gene-editing tool that only requires a custom guide RNA molecule to find its target, revolutionized the field.

CRISPR gene editing has quickly risen in popularity as a research tool because it makes genome editing much simpler and faster than ever before. The technology is also being researched as a potential treatment for a wide range of genetic diseases.

That is the case of CRISPR Therapeutics, a company that is running clinical trials testing the technology in two blood conditions as well as in cancer. Tony Ho, who leads research efforts at the company, shares his views on the potential of the technology and his expectations for the future of gene editing.

Genome editing technologies have been developed at a rapid pace over the past decade. Within the past five years, a novel system has been developed based on fundamental research of bacterial systems immunity to viral infections.

CRISPR-Cas9 is based on RNA-guided targeting and is much simpler and faster than earlier methods. The ease of design, together with the remarkable specificity, efficiency, and versatility of the CRISPR-Cas9 system have revolutionized the field of genome editing and enabled rapid development of novel therapies.

The advent of programmable nucleases has accelerated the development of gene editing from concept to clinic.Current advances in genome editing tools allow us not only to target monogenic diseases but also polygenic diseases, such as cancer and diabetes. Genomic editing also provides a degree of precision not previously possible by other therapeutic approaches through its ability to target individual cell types.

It also allows us to build on synthetic biology [techniques] that confer novel abilities to the cells. With these abilities, we can develop potentially curative therapies that may not be possible using traditional modalities.

The CRISPR-Cas9 system can modify DNA with greater precision than existing technologies. An advantage the CRISPR-Cas9 system offers over other mutagenic techniques, like ZFN and TALEN, is its relative simplicity and versatility.

Additionally,CRISPR-Cas9 has the potential of simultaneous multiple loci editing, making the technology easier, more efficient, and more scalable compared to other genome editing technologies.The programmability of the CRISPR-Cas9 system allows rapid prototyping of different therapeutic approaches, which leads to faster development cycles compared to other genome editing approaches.

While manufacturing is considered a challenge for the field, it is not a fundamental limitation. Companies are committed to overcoming challenges in order to bring medicines to patients at scale.

Additionally, its important to push the boundaries of what genome editing tools can offer to medicine. For example, its critical to move the field beyond therapeutic areas of rare diseases and hematologic malignancies, and into common diseases, like cancer and diabetes, where there is the potential to continue to see a dramatic impact and benefit to patients.

We expect to see increased enthusiasm for the gene editing field, particularly around CRISPR-Cas9, as it is a powerful platform that is facile and scalable. We believe the next generation of cell therapies will be driven by increased edits. We have published papers at oncology conferences that demonstrate that CRISPR-Cas9 can generate perfectly viable and enhanced CAR-T cells with 10 or more edits.

CRISPR-Cas9 is a revolutionary tool that can change the future of medicine. At CRISPR Therapeutics, we have five programs in the clinic, led by our two hematology programs, where we have demonstrated that a one-time CRISPR-based treatment can result in a functional cure for patients with sickle cell disease and beta-thalassemia.

We also have three ongoing clinical trials for allogeneic CAR-T therapies targeting B-cell malignancies, multiple myeloma, and renal cell carcinoma. Excitingly, we showed positive topline data in patients with relapsed or refractory B-cell malignancies, which demonstrate the potential of CRISPR gene editing for the treatment of cancers. We believe a number of cancers could be cured with CRISPR-based treatments, and we could replace a number of diseased or defective organs with regenerative medicine.

There is a world full of possibilities for CRISPR applications and I am very hopeful about what the future can bring.

This interview is part of Labiotechs report The Genome Editing Toolbox: ZFNs, TALENs, and CRISPR in Biomedicine. Become a member to get full access to this and many other reports offering a deep insight into the hottest areas of the biotech industry.

Follow this link:
The Promises of CRISPR Genome Editing in Biomedicine - Labiotech.eu

-New program expected to improve access to genetic testing for activated PI3K delta syndrome (APDS), an ultra-rare immunodeficiency disease

- Program has potential to advance clinical research in APDS as a result of earlier diagnosis

LEIDEN, The Netherlands, March 2, 2021 /PRNewswire/ -- Pharming Group N.V. ("Pharming" or "the Company") (Euronext Amsterdam: PHARM/Nasdaq: PHAR), a global, commercial stage biopharmaceutical company developing innovative protein replacement therapies and precision medicines for the treatment of rare diseases and unmet medical needs, in collaboration with Invitae Corporation (NYSE: NVTA, "Invitae"), a leading medical genetics company, announces the launch of a sponsored genetic testing program, navigateAPDS, designed to assist clinicians in identifying patients and their family members with activated PI3K delta syndrome (APDS), which may lead to earlier diagnosis.

APDS is an ultra-rare primary immunodeficiency disease caused by a genetic mutation affects approximately 1-2 people per million. Patients are often misdiagnosed with other immunodeficiencies or autoimmune disorders and often have a protracted course to obtain a correct diagnosis. A definitive diagnosis can be made only by a genetic test. Current treatment is generally limited to supportive therapies such as antibiotics and the use of immunoglobulin replacement therapy. There is no approved therapy for the treatment of APDS, however, clinical trials are currently ongoing, including Pharming's pivotal-stage development program for leniolisib, a small molecule phosphoinositide 3-kinase delta (PI3K) inhibitor, under development by Novartis and Pharming to treat patients with APDS.

Pharming's support of the program will facilitate genetic testing and counselling for eligible individuals in the United States and Canada at no charge. NavigateAPDS will use the Invitae Primary Immunodeficiency Panel (PI), which analyzes up to 407 genes that are associated with inherited disorders of the immune system. In addition to providing genetic testing to individuals who may present with a clinical picture known to be associated with APDS, navigateAPDS will offer pre-test and post-test genetic counseling through a third party, and all blood relatives of patients found to have a P/LP variant for APDS are qualified to be tested through the program. By offering access to the full PI panel, physicians and patients are more likely to identify the underlying cause and potential diagnosis without the need for additional expanded patient testing.

Sijmen de Vries, Chief Executive Officer commented:

"Our partnership with Invitae is an important step towards simplifying access to testing, which may allow for an expedited and accurate diagnosis for patients suffering from a primary immunodeficiency such as APDS. Earlier diagnosis can favorably impact disease management and could have a positive effect on long-term outcomes and patients' quality of life. The program is also a key component in advancing clinical research by identifying the underlying causes of APDS, which will help us better understand these patients' potential to respond to investigational precision medicines."

Robert Nussbaum, M.D., Chief Medical Officer of Invitae commented:

"Genetic information is a powerful tool that can improve outcomes for patients and their families, both by supporting more rapid diagnosis of ultra-rare diseases such as APDS and also by enabling access to clinical trials. Partnerships like our work with Pharming may enable the clinical trials necessary to develop precision therapies in areas of significant unmet need."

To learn more about the navigateAPDS program, visit http://www.invitae.com/navigateapds.

About APDS

APDS is an ultra-rare primary immunodeficiency first fully described in 2013 that affects approximately 1-2 people per million. APDS occurs when there is an abnormal change in either one of two specific genes, the PIK3CD gene or the PIK3R1 gene. The genes follow an autosomal dominant mode of inheritance which means one copy of the altered gene from either biological parent is sufficient to cause the disorder. The genes are involved in making parts of a protein that helps in the growth and division of white blood cells, particularly the B-cell and T-cell lymphocytes. APDS is present at birth and signs and symptoms start early in childhood with affected individuals having increased susceptibility to a myriad of inflammatory conditions including recurrent severe respiratory tract infections, chronic benign lymphoproliferation, hematopoietic malignancies, and/or autoimmune diseases. Patients are often misdiagnosed with other immunodeficiencies or autoimmune disorders and often have a protracted course to obtain a correct diagnosis. A definitive diagnosis can only be made by a genetic test and, once appropriately identified, regular specialized health check-ups and customized treatment plans are required. Current treatment is generally limited to supportive therapies such as antibiotics and the use of immunoglobulin replacement therapy. There is no approved therapy for the treatment of APDS, however, clinical trials are currently ongoing.

To learn more, visit http://www.allaboutapds.com.

About Pharming Group N.V.

Pharming Group N.V. is a global, commercial stage biopharmaceutical company developing innovative protein replacement therapies and precision medicines for the treatment of rare diseases and unmet medical needs.

The flagship of our portfolio is our recombinant human C1 esterase inhibitor, or rhC1INH, franchise. C1INH is a naturally occurring protein that downregulates the complement cascade in order to control swelling in affected tissues.

Our lead product, RUCONEST is the first and only plasma-free rhC1INH protein replacement therapy. It is approved for the treatment of acute hereditary angioedema, or HAE, attacks. We are commercializing RUCONEST in the United States, the European Union and the United Kingdom through our own sales and marketing organization, and the rest of the world through our distribution network.

We are also developing rhC1INH for subsequent indications, including pre-eclampsia, acute kidney injury and we also investigating the clinical efficacy of rhC1INH in COVID-19.

In addition, we are studying our oral precision medicine, leniolisib (a phosphoinositide 3-kinase delta, or PI3K delta, inhibitor), for the treatment of activated PI3K delta syndrome, or APDS, in a registration enabling Phase 2/3 study in the United States and Europe.

Furthermore, we are also leveraging our transgenic manufacturing technology to develop next-generation protein replacement therapies most notably for Pompe disease, which program is currently in the preclinical stage.

For more information please visit the company's website: http://www.pharming.com.

About Invitae

Invitae Corporation (NYSE: NVTA) is a leading medical genetics company, whose mission is to bring comprehensive genetic information into mainstream medicine to improve healthcare for billions of people. Invitae's goal is to aggregate the world's genetic tests into a single service with higher quality, faster turnaround time, and lower prices. For more information, visit the company's website at http://www.invitae.com.

Forward-looking Statements

This press release contains forward-looking statements, including with respect to timing and progress of Pharming's preclinical studies and clinical trials of its product candidates, Pharming's clinical and commercial prospects, Pharming's ability to overcome the challenges posed by the COVID-19 pandemic to the conduct of its business, and Pharming's expectations regarding its projected working capital requirements and cash resources, which statements are subject to a number of risks, uncertainties and assumptions, including, but not limited to the scope, progress and expansion of Pharming's clinical trials and ramifications for the cost thereof; and clinical, scientific, regulatory and technical developments. In light of these risks and uncertainties, and other risks and uncertainties that are described in Pharming's 2019 Annual Report and its report for the nine months ended 30 September 2020, the events and circumstances discussed in such forward-looking statements may not occur, and Pharming's actual results could differ materially and adversely from those anticipated or implied thereby. Any forward-looking statements speak only as of the date of this press release and are based on information available to Pharming as of the date of this release.

Inside Information

This press release relates to the disclosure of information that qualifies, or may have qualified, as inside information within the meaning of Article 7(1) of the EU Market Abuse Regulation.

For further public information, contact:

Pharming Group, Leiden, The NetherlandsSijmen de Vries, CEO: T: +31 71 524 7400Susanne Embleton, Investor Relations Manager: +31 71 524 7400/[emailprotected]

Invitae, San Francisco, USACorporate CommunicationsLaura D'AngeloE: [emailprotected]

FTI Consulting, London, UKVictoria Foster Mitchell/Mary Whittow/Alex Shaw, T: +44 203 727 1000

LifeSpring Life Sciences Communication, Amsterdam, The NetherlandsLeon MelensT: +31 6 53 81 64 27E: [emailprotected]

SOURCE Pharming Group N.V.

View original post here:
Pharming Group, in collaboration with Invitae Corporation, launches genetic testing program 'navigateAPDS' in US and Canada - PRNewswire

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Tenaya Therapeutics, a biotechnology company whose mission is to discover, develop and deliver curative therapies that address the underlying causes of heart disease, today announced that it has secured $106 million in Series C funding. Founded by leading cardiovascular scientists from the Gladstone Institutes and UT Southwestern (UTSW), Tenaya is advancing programs across three therapeutic platforms to address heart disease: Gene Therapy, Cellular Regeneration and Precision Medicine.

The Series C financing was led by RTW Investments, LP and adds new investors RA Capital Management, Fidelity Management & Research Company and funds and accounts advised by T. Rowe Price Associates, Inc. with additional participation from all existing investors including The Column Group, Casdin Capital, GV and others.

The new funding will allow Tenaya to advance its lead gene therapy program towards clinical studies; progress new programs towards IND-enabling studies; build on existing drug discovery and development capabilities across its three platforms; and invest in cGMP manufacturing capabilities.

Heart disease remains the leading cause of death in the world despite improvements in standards of care, said Faraz Ali, Chief Executive Officer of Tenaya. There is tremendous promise in the use of vastly more sophisticated tools for drug discovery available today to pioneer new classes of targeted treatments for heart failure, including potentially one-time curative gene therapies for genetic cardiomyopathies. We appreciate the strong support of new and existing investors who are helping us advance therapies to improve and extend the lives of patients.

Emerging Portfolio

Tenaya is advancing diverse and differentiated therapeutic approaches to gene therapy and small molecules for both prevalent and rare forms of heart disease:

Drug Development Capabilities

Since its Series B funding round announced in 2019, Tenaya has added to the depth and breadth of its drug discovery capabilities to support the efficacy, safety and differentiation of current and future products:

AAV Manufacturing

Tenaya also announced important steps towards internalizing its AAV manufacturing capabilities, expertise and IP to support its emerging portfolio of gene therapy products:

Tenaya has successfully built on its distinguished scientific heritage to advance a bold research strategy and differentiated drug discovery capabilities uniquely focused on heart disease, said Roderick Wong, M.D., Managing Partner and Chief Investment Officer at RTW Investments, LP. We are strong believers in the potential for new approaches in this area of high unmet need and are encouraged by early results we are seeing in the industry with the use of AAV to treat genetic forms of heart disease. We are excited to partner with Tenaya to accelerate their leadership position in this exciting field and to advance novel therapies that can benefit individuals and families fighting heart disease.

About Tenaya Therapeutics

Tenaya Therapeutics is shaping the future of heart disease treatment driven by a bold mission: to discover, develop and deliver curative therapies that address the underlying drivers of heart disease. Tenaya is developing therapies for rare genetic disorders as well as for more prevalent heart conditions through three platforms: Gene Therapy, Cellular Regeneration and Precision Medicine. Founded by leading cardiology researchers at the Gladstone Institutes and UT Southwestern, Tenaya is backed by a top-tier syndicate of investors. For more information, please visit http://www.TenayaTherapeutics.com and follow us on LinkedIn.

See original here:
Tenaya Therapeutics Secures $106 Million in Series C Funding to Accelerate Pipeline of Potentially Curative Therapies for Heart Disease - Business...

A Phase 1 trial will evaluate the use of gene therapy in delivering brain-derived neurotrophic factor (BDNF) to the brains of people with Alzheimers disease or mild cognitive impairment (MCI), which often precedes dementia.

Researchers at the University of California San Diego (UCSD) School of Medicine are preparing to open a three-year trial in 12 people diagnosed with either with Alzheimers or MCI, according to a universitypress release. The release did not specify if eligible patients need to be at particular stages of Alzheimers.

The trial will assess the safety and efficacy of injecting the BDNF gene, carried on an engineered adeno-associated virus (AAV2), directly to certain brain regions in these 12 patients.

Another 12 people will serve as an untreated control group for comparison.

BDNF is a neurotrophin, a protein that promotes the growth and survival of both new and existing neurons. The protein also functions as a neurotransmitter, mediating communication between nerve cells.

It is active in several brain regions susceptible to degeneration over the course of Alzheimers. Past research has identified mutations in the BDNFgene that impair its signaling ability, and which associate with faster cognitive decline and a higher risk of developing Alzheimers.

The research team conducting the trial previously found that BDNF could prevent and reverse brain cell degeneration and death in rat, monkey, and mouse models of Alzheimers.

We found that delivering BDNF to the part of the brain that is affected earliest in Alzheimers disease the entorhinal cortex and hippocampus was able to reverse the loss of connections and to protect from ongoing cell degeneration, said Mark Tuszynski, MD, PhD, senior author of a 2009 study of this preclinical work.

The entorhinal cortex produces BDNF and functions as a hub for memory, navigation, and the perception of time. Although it normally produces BDNF throughout a persons life, people with Alzheimers tend to produce less of it.

The investigators plan to deliver the BDNF gene to patients via AAV2 because the BDNF protein is too large to cross the blood-brain barrier. The injections will be targeted to specific brain areas, as too much freely circulating BDNF can cause harmful side effects such as seizures.

UCSD has participated in past Alzheimers gene therapy trials, which used an AAV vector to deliver a different neurotrophin named nerve growth factor (NGF) to the brain. The university reports that data from one past trial showed increased nerve growth, the formation of new nerve connections, and activation of functional markers in participants brains.

Tuszynski believes that therapeutic BDNF represents an improvement over trials using NGF.

BDNF is a more potent growth factor than NGF for neural circuits that degenerate in [Alzheimers], he said. In addition, new methods for delivering BDNF will more effectively deliver and distribute it into the entorhinal cortex and hippocampus.

The upcoming trial will be the first to evaluate the use of AAV2BDNF in humans.

BDNFgene therapy has the potential, unlike other [Alzheimers] therapies currently under development, to rebuildbrain circuits, slow cell loss and stimulate cell function, Tuszynski said. We are looking forward to observing the effects of this new effort in patients with [Alzheimers] and MCI.

Anyone wanting more information on this Phase 1 trial can contact Michelle Mendoza at 858-822-7438 or by sending an email to [emailprotected].

Total Posts: 282

Ana holds a PhD in Immunology from the University of Lisbon and worked as a postdoctoral researcher at Instituto de Medicina Molecular (iMM) in Lisbon, Portugal. She graduated with a BSc in Genetics from the University of Newcastle and received a Masters in Biomolecular Archaeology from the University of Manchester, England. After leaving the lab to pursue a career in Science Communication, she served as the Director of Science Communication at iMM.

Originally posted here:
Next:Phase 1 Trial to Test BDNF Gene Therapy in Alzheimer's Patients - Alzheimer's News Today

After spending around $200 and sending a vial of spit in the mail, almost anyone can gain access to an analysis of their DNA, learning their risk levels for everything from breast cancer to Parkinson's disease. But oncologist and geneticist Kenan Onel, MD, PhD, explains that direct-to-consumer genetic testing doesn't provide the context needed to give you comprehensive results.

"I really don't think that these tests, from a medical or a health perspective, are useful. I don't think that they're interpretable," says Dr. Onel, who is the director of the Center for Cancer Prevention and Wellness at the Icahn School of Medicine at Mount Sinai. "Clinical tests and a 23andMe test or an Ancestry.com test just have different goals and different designs."

On the heels of Ancestry discontinuing its medical branchAncestryHealth, recent research looked at single nucleotide polymorphism (SNP) tests, the kind of tests used by direct-to-consumer DNA testing companies like AncestryHealth and 23andMe. They found that while they're great at searching for common variants, the tests become inaccurate when screening for rare genetic mutations for disease-carrying genes. For example, when testing for mutations in BRCA1 and BRCA2 genes (genes that put you at a higher risk of developing breast and/or ovarian cancer), the probability that subjects with a positive screening test truly had the gene was only 4.2 percent.

Dr. Onel, who is also the associate director of clinical cancer genetics and precision oncology at The Tisch Cancer Institute at Mount Sinai, explains that this is because SNP tests are genotypes from samples of people. So the more rare a mutation is, the smaller the pool of genotypes available to base results on. Basing results on SNP tests alone leads to incomplete results because they lack the nuance that's available from more robust testing that would be performed, and later interpreted, by a geneticist.

"That's why genetics is a medical profession," says Dr. Onel. "Each and every one of us, we have somewhere between 10 and 30 million variants. Given that large number of variations, you can be sure that the vast majority of these tests are completely meaningless, but some of it may have implications for wellness and illness."

In addition to offering an incomplete picture, the results from these tests are often given in relative, instead of absolute, terms. "The sort of information that you get is, 'Oh, you have a 20 percent greater likelihood than other people of having chronic stomach aches.' Twenty percent sounds like a really big deal, that's one in five. I would really panic if I was told that I have 20 percent increased risk for something," says Dr. Onel. "But what that actually means is 20 percent greater than the background rate. So if the background rate of stomach aches is one in 10, having a 20 percent increased risk means that you're now at a whopping 1.2 in 10. The problem with direct-to-consumer testing is that nobody understands probability theory. Nobody understands actually what they're telling you when they give you these percentages."

Dr. Onel says if you're serious about understanding how your genetics could impact your health, he says to seek out a geneticist instead of buying a direct-to-consumer genetic test.

"I wouldn't use them for anything clinicalI would use them because they're fun, because they're cheap, because they're entertaining," he says. "And it's like, 'Oh, look, I'm supposed to have blue hairin fact, I do. Hahaha!' That's great, but I don't think that you can actually draw meaningful medical conclusions, health conclusions, from these sort of direct-to-consumer tests right now."

Oh hi! You look like someone who loves free workouts, discounts for cult-fave wellness brands, and exclusive Well+Good content. Sign up for Well+, our online community of wellness insiders, and unlock your rewards instantly.

See the rest here:
Im a Geneticist, and This Is What Direct-to-Consumer Tests Can (and Cant) Tell You About Your Health - Well+Good

SALT LAKE CITY (ABC4) A new study may take the guilt out of wanting to take a nap.

Many animals who are awake during the day and sleep at night take naps. Dogs, flies, and people. But what makes some people morning people, night people, and nap people?

New research suggests it may be in your genes especially the urge to take a nap.

Call it what you will, a power nap, a siesta, or just an afternoon dropout. Researchers have learned that people who like to take naps share some genetic traits that may make them enjoy naps.

In the largest study of its kind, a team led by Harvard Investigators at Harvard-affiliated Massachusetts General Hospital (MGH) collaborated with colleagues at the University of Murcia in Spain and several other institutions then published inNature Communications.

The study says, Naps are short daytime sleep episodes that are evolutionarily conserved across diverse diurnal species ranging from fliesto polyphasic mammals. In human adults, daytime napping is highly prevalent in Mediterranean cultures and is also common in non-Mediterranean countries including the United States

The study discovered dozens of gene regions that govern the tendency to take naps during the day.

In a statement to the Harvard Gazette, Napping is somewhat controversial, says Hassan Saeed Dashti of the MGH Center for Genomic Medicine, co-lead author of the report with Iyas Daghlas, a medical student at Harvard Medical School (HMS). Dashti notes that some countries where daytime naps have long been part of the culture (such as Spain) now discourage the habit. Meanwhile, some companies in the United States now promote napping as a way to boost productivity.

It was important to try to disentangle the biological pathways that contribute to why we nap, says Dashti.

Researchers first used the UK Biobank data for the GWAS (genome-wide association study), which holds the genetic information on 452,633 people. The participants were asked whether they nap during the day never/rarely, sometimes, or usually.

Some of the participants wore accelerometers to monitor their activity during the day.

The accelerometers helped the researchers determine if the responses from the people matched with activity. That gave an extra layer of confidence that what we found is real and not an artifact, says Dashti.

The team discovered certain genes play a factor, according to the results posted in the Harvard Gazette. People who needed naps expressed the need and the reason why differently.

The study says, Genetic variation constitutes an important contributor to inter-individual differences in napping preference. A twin study estimated heritability of self-reported napping and objective daytime sleep duration to be 65% and 61%, respectively, demonstrating heritability similar or even higher than heritability found for other sleep traits such as nighttime sleep duration and timing

Once they dug into the data the team discovered different mechanisms in each of us that promotes napping.

What does it all mean? They all needed naps.

This tells us that daytime napping is biologically driven and not just an environmental or behavioral choice, says Dashti.

Here is the original post:
Want to take a nap? Dont feel guilty, it might be in your genes - ABC 4

For the third year in a row, a discovery from the University of Virginia School of Medicine has been selected as one of the years most significant biomedical discoveries. The finding identifying the gene responsible for one of the deadliest cancers is among 64 contenders fighting it out to win the publics votes in an online bracket tournament.

Voting opens today for STAT Madness, which is like the scientific version of the NCAA basketball tournament. The annual competition is sponsored by the STAT health news site to identify the years best biomedical innovation, and you can vote by clicking here. The first round is open through Sunday.

UVA is one of 64 competitors in the first round of the tournament, which features a roster of scientific heavy hitters. Other top institutions that have made it to the first round include Duke University, Stanford University, the University of Notre Dame and the Massachusetts Institute of Technology.

The UVA discoverys first-round opponent is the discovery of a genetic risk factor for melanoma, from Rockefeller University.

UVAs entry comes from researcher Hui Li and his collaborators, who identified the oncogene (a cancer-causing gene) responsible for glioblastoma, an aggressive form of brain cancer.The discoveryoffers a promising new treatment target for a cancer that is often fatal within a year of diagnosis.

Li and his colleagues say the oncogene is essential to the survival of glioblastoma cells. Without it, they found, the cancer cells die. Scientists have already developed many targeted therapies for other cancers with a similar oncogene addiction, and Li hopes his discovery will lead to more effective treatments for glioblastoma.

We feel honored that our work has been selected as one of the top discoveries, but even more honored to be able to provide some hope to the patients with this deadly disease, said Li, of UVAs Department of Pathology and the UVA Cancer Center. We believe thisAVILgene is one of the Achilles heels of glioblastoma, and are working hard to figure out a way to target it.

The 64 finalists in this years STAT Madness were winnowed from more than 130 submissions from universities and affiliated research institutions.

This is the third year in a row UVA has made the cut. Last years contest featured an artificial pancreas developed at UVA that automatically regulates blood sugar for people with type 1 diabetes. The previous years contest featured a game-changing neuroscience discovery revealing the existence of tiny vessels connecting the brain to the immune systemvessels that textbooks had long insisted did not exist.

Its wonderful to see outstanding work from the School of Medicine consistently recognized among the years most exciting and promising biomedical discoveries, said Dr. K. Craig Kent, UVAs executive vice president for health affairs. Its a testament to the caliber of the research being conducted here, and Im proud to see our institution performing important work that will ultimately benefit the health and lives of people everywhere.

To keep up with the latest medical research news from UVA, subscribe to theMaking of Medicineblog.

Excerpt from:
Cancer Find Up for Year's Biggest Biomedical Advance in a Different 'March Madness' - University of Virginia