BETHESDA, Md., July 30, 2020 /PRNewswire/ --The ACMG Foundation for Genetic and Genomic Medicine announced today that Nasha Fitter has been elected to its board of directors. The ACMG Foundation is a national nonprofit foundation dedicated to facilitating the integration of genetics and genomics into medical practice. The board members are active participants, serving as advocates for the ACMG Foundation and for advancing its policies and programs. Ms. Fitter was elected to a two-year term starting immediately.

ACMG Foundation President Bruce R. Korf, MD, PhD, FACMG said, "I am delighted to welcome Nasha Fitter to the ACMG Foundation board as a public member.Nasha has a passion for improving the lives of individuals who are affected with genetic conditions, and also has extraordinary skills in business, education and technology.She is superbly qualified to represent the interests of the public on the ACMG Foundation board."

Ms. Fitter has a background in healthcare and education. She currently serves as director of Rare and Neurological Diseases at Ciitizen, where she and her team generate regulatory-grade longitudinal data for natural history studies, synthetic control arm and post-approval studies for rare and neurological diseases. She is also co-founder, CEO, and head of research at FOXG1 Research Foundation, an organization she launched after her daughter was diagnosed with FOXG1 syndrome. The foundation is focused on finding a cure for this severe disease and is working to build global expertise on FOXG1 neurobiology and a repository of patient clinical outcomes. Previously, Ms. Fitter founded and served as CEO of Schoolie, a technology company that collected data on school performance across the US and shared actionable analysis with parents and policymakers. She also worked as director of the Global Schools Program at Microsoft Education, Microsoft's premier global program for K12 schools. Ms. Fitter earned a Bachelor of Science from the University of Southern California and an MBA from Harvard Business School.

About her election to the ACMG Foundation Board of Directors, Ms. Fitter said, "In the next few years we will see the immense power of genetic medicine in saving and transforming people's lives. I am thrilled to be joining an organization at the forefront of this incredible science and look forward to working with such a diverse and experienced board."

A complete roster of the ACMG Foundation board can be found at http://www.acmgfoundation.org.

About the ACMG Foundation for Genetic and Genomic Medicine

The ACMG Foundation for Genetic and Genomic Medicine, a 501(c)(3) nonprofit organization, is a community of supporters and contributors who understand the importance of medical genetics and genomics in healthcare. Established in 1992, the ACMG Foundation supports the American College of Medical Genetics and Genomics (ACMG) mission to "translate genes into health." Through its work, the ACMG Foundation fosters charitable giving, promotes training opportunities to attract future medical geneticists and genetic counselors to the field, shares information about medical genetics and genomics, and sponsors important research. To learn more and support the ACMG Foundation mission to create "Better Health through Genetics" visit acmgfoundation.org.

Kathy Moran, MBA [emailprotected]

SOURCE American College of Medical Genetics and Genomics

http://www.acmgfoundation.org

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Nasha Fitter Elected to Board of Directors of the ACMG Foundation for Genetic and Genomic Medicine - PRNewswire

Newswise Genetic modifier HDAC6 was found to control tumor growth and halt metastasis in triple-negative breast cancer in vivo, according to a new study published in the top-tier journal Cancer Research by investigators at the George Washington University (GW) Cancer Center.

Immunotherapy the use of drugs to stimulate ones own immune system to recognize and destroy cancer cells has been wildly successful in melanoma and other cancers. However, it has been less effective in breast cancer.

There is an urgent medical need to find new ways to potentiate or increase the efficacy of immunotherapy in breast cancer, especially in aggressive and highly metastatic triple-negative breast cancer, said Alejandro Villagra, PhD, member of the Cancer Biology Program at the GW Cancer Center and assistant professor of biochemistry and molecular medicine at the GW School of Medicine and Health Sciences. Our research lays the groundwork for a clinical trial that could lead to new, life-saving treatment options for breast cancer patients that do not respond to conventional immunotherapies.

Molecularly targeted agents, such as HDAC6 inhibitors, have been widely described in the research literature as cytotoxic toxic to both cancerous and healthy cells. Villagra and his research team found new non-canonical regulatory properties of these epigenetic drugs, discovering that the inhibition of HDAC6 has a powerful and strong effect on the immune system unrelated to the previously cytotoxic properties attributed to HDAC inhibitors.

This research demonstrates for the first time that HDAC6 inhibitors can both improve response to immunotherapy and diminish the invasiveness of breast cancer, with minimal cytotoxic effects.

We are excited about the work because, in addition to the potency of immunotherapy, this drug alone is capable of reducing metastasis, said Villagra. This could have implications beyond breast cancer.

This research was a multidisciplinary effort, made possible by collaborators across the GW Cancer Center, the GW School of Medicine and Health Sciences and the GW School of Engineering and Applied Sciences. The project was funded by grants from the GW School of Medicine and Health Sciences, the National Institutes of Health, and the Melanoma Research Foundation.

HDAC6 plays a non-canonical role in the regulation of anti-tumor immune responses, dissemination, and invasiveness of breast cancer was published in Cancer Research, a journal of the American Association for Cancer Research, and is available at https://cancerres.aacrjournals.org/content/early/2020/06/30/0008-5472.CAN-19-3738.

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HDAC6 Can Control Tumor Growth and Halt Metastasis in Triple-Negative Breast Cancer - Newswise

The promised democratization of biology plays out as industry frontrunners consolidate early leads and bio-preneurs consider the sheer breadth of opportunity

Today, anyone who can code can win in the internet economy. Thanks to services such as Amazons AWS and Apples App Store, only basic coding skills are needed to develop and distribute lucrative apps.

Similar enabling infrastructure is taking root in the field of synthetic biology, a scientific discipline that uses genetic tools to engineer microbes for a wide range of downstream use cases, from manufacturing the screens in our smartphones to producing the food we eat.

A recent McKinsey report estimates that there are at least 400 unique applications of synthetic biology across fields as diverse as medicine, agriculture, food, and chemicals. The potential market opportunities for end products alone exceeds four trillion dollars. Who will tap into this biological goldmine?

The creation of synthetic biology infrastructure, including low-cost genetic sequencing, automated cloud-accessed laboratories, and biology-as-a-service providers, could enable a democratized ecosystem similar to that seen in mobile app development as bio-preneurs identify profitable use cases for synthetic biology technology. But despite these empowering tools, the importance of big data and machine learning in synthetic biology an engineering problem with thousands of genetic and metabolomic inputs provides a counterforce that contributes to the development of a consolidated, winner-take-all ecosystem within the synthetic biology space.

The balance of power between the democratization of biologys toolset and the centralization of essential datasets and algorithms will dictate whether profits are accrued by a few synthetic biology titans or by a wide array of companies and entrepreneurs.

Synthetic biology apps come in two forms: a product produced by a microbe (such as silk or food protein), or the microbe itself (e.g., a bacterium that can substitute for traditional fertilizer). In both cases, there are typically three steps in the product development: First, identify the use case. Second, design the microbe. Third, manufacture the end-product.

Once a would-be bio-preneur has identified an app, there are both biology-as-a-service providers and low-cost, turnkey equipment manufacturers that drastically lower the expertise and capital barriers to entry for each of these steps in the synthetic biology process. Organizations such as Ginkgo Bioworks will cover your microbial design needs, Culture Biosciences can optimize your bio-manufacturing process, and a slew of biomanufacturing organizations can deliver on the end-product manufacturing. As this enabling infrastructure develops, synthetic biology product development could be so abstracted away from the core biology skill-set to enable even those without any specialized training to pursue cutting-edge synthetic biology apps at least, in theory.

This democratization is conceivable in theory. But early pioneers in the field have smartly capitalized on the digitization of biological data, creating the potential for a consolidation of value in the field.

The design of a microbe for any given purpose to produce a medicine or to sequester CO2 in the air is a complex process incorporating the interactions of hundreds or thousands of genes, proteins, and metabolic pathways. For this reason, human-led engineering may provide a starting-point, but only recent advances in machine learning can truly optimize this process. Early leaders in the synthetic biology space, particularly Zymergen, have developed massive chemical, genomic, proteomic, and metabolomic datasets, as well as near-fully automated laboratories to conduct high-throughput experiments that generate even more data every day. These datasets are then fed into machine-learning algorithms that predict the best molecule for a given purpose and the best microbe to produce that molecule. As the datasets grow, the machine-learning algorithms are perpetually trained to offer stronger and more optimal predictions.

This self-reinforcing feedback loop of experimentally-derived data and machine learning optimization has resulted in a moat that competitors will find tough to contend with. With this platform, Zymergen expects to be able to discover the best materials for a given use case, and the most efficient microbe for producing that material. And they expect to be able to do this more quickly and more cheaply than any competitor without similar data and algorithms to leverage.

Given this consolidation of ability, how could a synthetic biology competitor (or an aspiring bio-preneur) ever hope to compete?

The Zymergen juggernaut may seem intimidating to would-be entrepreneurs in the space, but there is still strategic space for bio-preneurs to target.

First, the sheer breadth of applications for biomanufacturing and synthetic biology broadly precludes a frontrunner like Zymergen from competing across all these use cases at least for now. With early identification of target applications, bio-preneurs can stake out profitable niches by developing persuasive biology and sticky commercialization models to disincentivize any future entrance by a company like Zymergen. This approach enables early-movers to establish a defensible moat around the production of certain relatively commoditized goods.

A second approach relies on developing expertise around a field which the machine-learning engines are not built to optimize. In industries such as medicine or food science, researchers can discover new microbes and molecules for a given use case that Zymergen may not be best equipped to predict. For example, companies discovering and designing new food items, such as Natures Fynd, are playing in a niche that has not yet been made vulnerable to Zymergens brand of machine-learning enabled disruption.

In a similar vein, companies inventing new ways to compete with Zymergen could find a competitive advantage in certain synthetic biology verticals. To this end, companies digitizing new types of data, including the next-generation proteomics championed by Nautilus Biotechnology, could begin to accumulate their own datasets that are advantageous within a given use case.

Finally, bio-preneurs would be well-advised to consider the old adage, If you cant beat em, join em. For entrepreneurs pursuing ingenious use cases for synthetic biology or innovative downstream business models that thrust engineered biology into the mainstream, leaders like Zymergen may not be a competitor, but a powerful and willing partner in the engineering of biology.

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Will programming a cell ever be as easy as programming an app? - SynBioBeta

Newswise PHILADELPHIAInherited mutations in a gene that keeps nerve cells intact was shown, for the first time, to be a driver of a neuropathy known as Charcot-Marie-Tooth (CMT) disease. This finding is detailed in a study led by researchers in the Perelman School of Medicine at the University of Pennsylvania, which published in Neurology Genetics, an official journal of the American Academy of Neurology.

The findings, thanks to siblings treated at Penn since the late 1980s, present a clearer picture of the diseases genetic underpinnings that could inform the development of gene therapies to correct it.

The mutations in the gene known as dystonin (DST) add to a growing list of malfunctions found to cause their type of CMT, known as CMT2, which is defined by the loss of the nerve fibers, or axons, in the peripheral nerve cells. The researchers also showed that these mutations affect two key protein isoforms, BPAG1-a2 and BPAG1-b2, that are involved in nerve fiber function. Mutations in other isoforms of the same protein were previously tied to a blistering skin disease.

Neuropathies are common, occurring in nearly half of all diabetic patients, while hereditary neuropathies affect nearly one of out of 2,000 people. CMT is a debilitating neurodegenerative disorder that usually strikes in the second or third decade of life, and leaves patients with numbness and weakness in the hands and feet, among other neurological-related conditions.

There are more than 100 mutations found to be associated with CMT, with likely many more out there. Past studies from Penn researchers have identified some of these mutations by studying patients treated at Penn Medicine.

We are determined to fill in the blanks of this giant jigsaw puzzle, said senior author Steven S. Scherer, MD, PhD, a professor of Neurology. This latest paper is but one of many examples of where breakthroughs have happened between patients and the doctors at Penn and the support of different organizations and institutions to bring it all together."

The researchers applied whole exome sequencing to analyze the more than 30 million base pairs of DNA that encode the 20,000 proteins in humans. By examining three siblingstwo affected and one unaffectedthe researchers were able to deduce the genetic basis of mutations that caused the two siblings to be affected.

Backed by a mouse model from past studies showing a role of dystonin in neuropathies, the researchers identified two recessive mutations on the DST gene, each received from a biological parent, as the culprit. Together, the two mutations in the affected siblings disrupt the BPAG1-a2 and BPAG1-b2 isoforms, the researchers found, which weakened their axonal health. The DST gene gives rise to proteins that regulate the organization and stability of the microtubule network of sensory neurons to allow for transport of different cellular material along the nerve fibers.

We have collaborated with this family for 30 years, and now we finally have an answer, Scherer said, and the answer was a new genetic cause of neuropathy.

The findings put the field steps closer to developing new targeted therapeutics as well as CMT gene therapies designed to replace missing genes or correct mutations driving the disease. Clinical trials to investigate these latest mutations and others are not far off in the future, the researchers believe, particularly at an institution like Penn, which is home to the second largest clinic for CMT patients in the country and well-known for its gene therapy program.

We are in the era where treatments for genetic diseases are possible, Scherer said. This brother and sister stand to benefit from that approach because we know the gene that is missing, and if we could replace it, that should at least prevent their progression.

Co-authors of the study include William Motley, MD, DPhil, a former medical student at Penn and now of Third Rock Ventures, a venture capital firm that invests in biotechnology, and Stephan Zuchner, MD, PhD, of the department of Human Genetics at the University of Miami.

This work was supported by the Judy Seltzer Levenson Memorial Fund for CMT Research, the INC (U54NS065712), which is a part of the NCATS Rare Diseases Clinical Research Network, an initiative of the Office of Rare Diseases Research, and in part by the National Institutes of Health (R25NS065729).

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Penn Medicineis one of the worlds leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of theRaymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nations first medical school) and theUniversity of Pennsylvania Health System, which together form a $8.6 billion enterprise.

The Perelman School of Medicine has been ranked among the top medical schools in the United States for more than 20 years, according toU.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $494 million awarded in the 2019 fiscal year.

The University of Pennsylvania Health Systems patient care facilities include: the Hospital of the University of Pennsylvania and Penn Presbyterian Medical Centerwhich are recognized as one of the nations top Honor Roll hospitals byU.S. News & World ReportChester County Hospital; Lancaster General Health; Penn Medicine Princeton Health; and Pennsylvania Hospital, the nations first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.

Penn Medicine is powered by a talented and dedicated workforce of more than 43,900 people. The organization also has alliances with top community health systems across both Southeastern Pennsylvania and Southern New Jersey, creating more options for patients no matter where they live.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2019, Penn Medicine provided more than $583 million to benefit our community.

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Penn Researchers Identify New Genetic Cause of a Form of Inherited Neuropathy - Newswise

A new meta-analysis tries to shed light on why strokes hit the black population harder than other groups.

Published in Stroke, the COMPASS (Consortium of Minority Population Genome-Wide Association Studies of Stroke) included more than 22,000 individuals of African ancestry from 13 different cohorts (3,734 cases and 18,317 controls).

Stroke is a complex disease with multiple genetic and environmental risk factors, the authors wrote. Blacks endure a nearly 2-fold greater risk of stroke and are 2 to 3 times more likely to die from stroke than European Americans.

The authors identified a single nucleotide polymorphism (rs55931441) near HNF1A gene that they reported had genome-wide significance (P=4.62108) along with at least 29 other polymorphisms at 24 unique loci that they said showed evidence of an association (P<1106). The authors compared this to other populations by performing a look-up analysis in Europeans and Hispanics (in the Stroke Genetics Network). Sixteen of 24 loci across multiple populations validated the findings for individuals of African descent. They also wrote that variants in the SFXN4andTMEM108 genes represented potential novel ischemic stroke loci.

Despite its limitations, the authors noted that genetic studies like COMPASS that include minority populations present potential for identifying underlying stroke disparities. The upshot, they said, was potential advances in precision medicine that would lead to better stroke risk stratification in diverse populations.

Given the undue burden that people of African ancestry endure from stroke and other cerebrovascular disease, the lack of investigation of risk factors in this group has been a substantial gap, said researcher Bradford B. Worrall, MD, a neurologist at UVA Health, in a press release. Our work is an important step toward filling that gap, albeit with much more work to be done. These findings will provide greater insight into ethnic-specific and global risk factors to reduce the second leading cause of death worldwide.

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Genetic Variant in Persons of African Descent Linked with Stroke: Analysis - DocWire News

SAN FRANCISCO, Aug. 4, 2020 /PRNewswire/ --Invitae Corporation (NYSE: NVTA), a leading medical genetics company, today announced financial and operating results for the second quarter ended June 30, 2020.

"While we experienced significant disruptions in the healthcare system due to the pandemic, we quickly established a solid recovery during the quarter. Our results highlight the strength of our operations and the benefits of our diversified menu, investments in telehealth capabilities and longstanding customer relationships, all of which position us to adapt and meet the changing needs of our customers," said Sean George, Ph.D., co-founder and chief executive officer of Invitae. "We exited the quarter with a strong footing and increasing momentum. We remain confident in our ability to continue to deliver on our mission to bring genetic information into mainstream medicine."

Second Quarter 2020 Financial Results

Total operating expense, excluding cost of revenue, for the second quarter of 2020 was $145.3 million. Non-GAAP operating expense was $105.7 million in the second quarter of 2020.

Net loss for the second quarter of 2020 was $166.4 million, or $1.29 net loss per share, compared to a net loss of $48.7 million in the second quarter of 2019, or $0.54 net loss per share. Non-GAAP net loss was $99.2 million, or $0.77 non-GAAP net loss per share, in the second quarter of 2020.

At June 30, 2020, cash, cash equivalents, restricted cash and marketable securities totaled $428.5 million. Net increase in cash, cash equivalents and restricted cash for the quarter was $78.0 million. Cash burn, including various acquisition-related expenses, was $89.2 million for the quarter and $63.8 million when excluding the $25.4 million cash paid to acquire YouScript and Genelex.

Early in the quarter, in response to impacts of the pandemic, the company took actions to significantly scale back operational expenditures. The result of these changes is expected to decrease the discretionary spend in cost of revenue and operating expense beginning in the third quarter.

"We continue to see a solid recovery in volume, improvement in our operating leverage and ability to improve revenue generation. As a result, we are well positioned with sufficient capital to execute our strategy in the coming years," continued Dr. George. "We have added or will be adding important capabilities to our platform through the acquisitions we announced this quarter and our ongoing product development efforts. With our mission clearly in focus, we can continue to navigate these unprecedented times."

Corporate and Scientific Highlights

Webcast and Conference Call DetailsManagement will host a conference call and webcast today at 4:30 p.m. Eastern / 1:30 p.m. Pacific to discuss financial results and recent developments. To register for the conference call and webcast, please use one of the methods below. Upon registering, each participant will be provided with call details and a registrant ID.

Online registration: http://www.directeventreg.com/registration/event/5882896

Phone registration: (888) 869-1189 or (706) 643-5902

The live webcast of the call and slide deck may be accessedhere or by visiting the investors section of the company's website atir.invitae.com. A replay of the webcast and conference call will be available shortly after the conclusion of the call and will be archived on the company's website.

About InvitaeInvitae 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 invitae.com.

Safe Harbor StatementThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements relating to the company's belief that it is well-positioned to adapt and meet the changing needs of its customers; the company's belief regarding the momentum of its business and ability to continue to deliver on its mission to bring genetic information into mainstream medicine; the impact of the COVID-19 pandemic on the company's business, and the measures it has taken or may take in the future with respect thereto; the impact of the company's acquisitions, including its proposed merger with ArcherDX, as well as its partnerships and product offerings; and the company's beliefs regarding the growth of its business, its position and impact on the genetic testing industry, its success in executing on its mission and strategy, and the benefits of genetic testing. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially, and reported results should not be considered as an indication of future performance. These risks and uncertainties include, but are not limited to: the impact of the COVID-19 pandemic on the company, and the effectiveness of the efforts it has taken or may take in the future in response thereto; the company's ability to continue to grow its business, including internationally; the company's history of losses; the company's ability to compete; the company's failure to manage growth effectively; the company's need to scale its infrastructure in advance of demand for its tests and to increase demand for its tests; the risk that the company may not obtain or maintain sufficient levels of reimbursement for its tests; the ability of Invitae and ArcherDX to obtain the approval of Invitae's and ArcherDX's stockholders, and to satisfy the other conditions to the closing of the acquisition and related financing transactions on a timely basis or at all; the occurrence of events that may give rise to a right of one or both of Invitae and ArcherDX to terminate the merger agreement; the company's failure to successfully integrate or fully realize the anticipated benefits of acquired businesses; the company's ability to use rapidly changing genetic data to interpret test results accurately and consistently; security breaches, loss of data and other disruptions; laws and regulations applicable to the company's business; and the other risks set forth in the company's Quarterly Report on Form 10-Q for the quarter ended March 31, 2020. These forward-looking statements speak only as of the date hereof, and Invitae Corporation disclaims any obligation to update these forward-looking statements.

Non-GAAP Financial MeasuresTo supplement Invitae's consolidated financial statements prepared in accordance with generally accepted accounting principles in the United States (GAAP), the company is providing several non-GAAP measures, including non-GAAP gross profit, non-GAAP cost of revenue, non-GAAP operating expense, including non-GAAP research and development, non-GAAP selling and marketing, non-GAAP general and administrative and non-GAAP other income (expense), net, as well as non-GAAP net loss and non-GAAP net loss per share and non-GAAP cash burn. These non-GAAP financial measures are not based on any standardized methodology prescribed by GAAP and are not necessarily comparable to similarly-titled measures presented by other companies. Management believes these non-GAAP financial measures are useful to investors in evaluating the company's ongoing operating results and trends.

Management is excluding from some or all of its non-GAAP operating results (1) amortization of acquired intangible assets, (2) acquisition-related stock-based compensation related to inducement grants, (3) post-combination expense related to the acceleration of equity grants or bonus payments in connection with the company's business combinations, (4) adjustments to the fair value of our acquisition-related liabilities and (5) acquisition-related income tax benefits. These non-GAAP financial measures are limited in value because they exclude certain items that may have a material impact on the reported financial results. Management accounts for this limitation by analyzing results on a GAAP basis as well as a non-GAAP basis and also by providing GAAP measures in the company's public disclosures.

Cash burn excludes (1) changes in marketable securities, (2) cash received from equity financings and (3) cash received from exercises of warrants. Management believes cash burn is a liquidity measure that provides useful information to management and investors about the amount of cash consumed by the operations of the business. A limitation of using this non-GAAP measure is that cash burn does not represent the total change in cash, cash equivalents, and restricted cash for the period because it excludes cash provided by or used for other operating, investing or financing activities. Management accounts for this limitation by providing information about the company's operating, investing and financing activities in the statements of cash flows in the consolidated financial statements in the company's most recent Quarterly Report on Form 10-Q and Annual Report on Form 10-K and by presenting net cash provided by (used in) operating, investing and financing activities as well as the net increase or decrease in cash, cash equivalents and restricted cash in its reconciliation of cash burn.

In addition, other companies, including companies in the same industry, may not use the same non-GAAP measures or may calculate these metrics in a different manner than management or may use other financial measures to evaluate their performance, all of which could reduce the usefulness of these non-GAAP measures as comparative measures. Because of these limitations, the company's non-GAAP financial measures should not be considered in isolation from, or as a substitute for, financial information prepared in accordance with GAAP. Investors are encouraged to review the non-GAAP reconciliations provided in the tables below.

INVITAE CORPORATION

Consolidated Balance Sheets

(in thousands)

(unaudited)

June 30,2020

December 31,2019

Assets

Current assets:

Cash and cash equivalents

$

168,203

$

151,389

Marketable securities

253,933

240,436

Accounts receivable

27,905

32,541

Prepaid expenses and other current assets

21,081

18,032

Total current assets

471,122

442,398

Property and equipment, net

43,381

37,747

Operating lease assets

38,239

36,640

Restricted cash

6,343

6,183

Intangible assets, net

192,644

125,175

Goodwill

211,225

126,777

Other assets

6,921

6,681

Total assets

$

969,875

$

781,601

Liabilities and stockholders' equity

Current liabilities:

Accounts payable

$

20,091

$

10,321

Accrued liabilities

99,490

64,814

Operating lease obligations

6,339

4,870

Finance lease obligations

977

1,855

Total current liabilities

126,897

81,860

Operating lease obligations, net of current portion

42,134

42,191

Finance lease obligations, net of current portion

879

1,155

Convertible senior notes, net

276,092

268,755

Deferred tax liability

10,250

Other long-term liabilities

Continued here:

Invitae Reports $46.2 Million in Revenue Driven by More Than 120000 Samples Accessioned in the Second Quarter of 2020 - Monterey County Weekly

ByCarly Kempler

Noel R. Rose, a longtime Johns Hopkins Bloomberg School of Public Health faculty member and researcher widely recognized as a father of autoimmune disease research, died Thursday at home in Brookline, Massachusetts. He was 92.

"Noel was an extraordinary scientist and an exceptionally kind and humble human beingalways looking out for the well-being of faculty and students," said Ellen J. MacKenzie, the current dean of the Johns Hopkins Bloomberg School of Public Health. "I admired his steadfast commitment to excellence coupled with his dry sense of humor. He was always good at listening to different sides of an argument and reaching a decision that everyone felt good about."

Rose served from 1951 to 1973 on the faculty of SUNY Buffalo School of Medicine, where he and his mentor Ernest Witebsky discovered in 1956 that Hashimoto's diseasechronic lymphocytic thyroiditis, or hypothyroidismcould be reproduced in experimental animals by immunization with thyroglobulin, which revealed that animals produced an immune response that inflamed and destroyed their own thyroid glands. This landmark discovery of autoimmunity led to the creation of a whole new class of disease and opened the door for research for treatments and cures.

Image caption: Noel R. Rose

He then discovered the genetic basis of autoimmune disease. His lab showed for the first time that the major histocompatibility complex contains the main genes that determine the risk for all autoimmune disease. From 1973 to 1982, he was professor and chair of the Department of Immunology and Microbiology at Wayne State University School of Medicine.

Rose joined Johns Hopkins in 1982 as chair of what was then known as the Department of Immunology and Infectious Diseases and is now the W. Harry Feinstone Department of Molecular Microbiology and Immunology at the Bloomberg School. He held a full-time joint appointment in the Johns Hopkins School of Medicine's Department of Pathology, where he directed the Pathobiology Graduate Program.

After stepping down as chair in 1993, Rose directed the Department of Pathology Division of Immunology for five years and served as president of the Bloomberg School Faculty Senate. He also directed the Johns Hopkins Center for Autoimmune Disease Research, which he founded in 1999.

"As his successor as department chair, I benefitted greatly from Noel's perspective and advice. In his own quiet and considerate way, he contributed to science and the School of Public Health in multiple ways," recalled Diane Griffin, University Distinguished Service Professor at the Bloomberg School who served as chair of Molecular Microbiology and Immunology from 1994 through 2014. "He was a founding contributor to the field of autoimmunity and continued to make pioneering contributions to our understanding of these diseases."

Rose was born in Stamford, Connecticut, on December 3, 1927. His mother was a homemaker and his father a physician. He received his bachelor's degree in zoology in 1948 from Yale University, a PhD in medical microbiology from University of Pennsylvania in 1951, and his MD in 1964 from the State University of New York, Buffalo.

His numerous accolades include the Abbot Award, Professional Recognition Award, and Founder's Distinguished Service Award from the American Society for Microbiology; Ernest Lyman Stebbins Medal from Johns Hopkins Bloomberg School of Public Health, the Bloomberg School's most prestigious award; Nikolaus Copernicus Medal from the Polish Academy of Sciences; Presidential Award from the Clinical Immunology Society, and Golden Goose Award from the American Association for the Advancement of Science.

His prominent national and global leadership roles included director of the Pan American Health Organization/World Health Organization Collaborating Center for Autoimmune Disorders and chair of the Autoimmune Diseases Coordinating Committee at the National Institutes of Health. Rose was editor or co-editor of 23 books, most notably the textbook The Autoimmune Diseases, and published more than 880 articles and chapters in the fields of immunology, immunopathology, autoimmunity, and autoimmune diseases.

In 1991, Rose and Virginia T. Ladd founded the American Autoimmune Related Diseases Association, the primary research and advocacy group for autoimmune diseases. For 20 years, Rose chaired the organization's scientific committee and spearheaded the biannual Noel R. Rose Scientific Colloquium, which convenes the nation's leading researchers in autoimmune and related diseases.

Rose is survived by his wife of 69 years, Deborah H. Rose; children Alison Rose Weinstock, David Richard Rose, Bethany Rose Kramer, and Jonathan Richard Rose; 10 grandchildren; and five great-grandchildren.

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Noel R. Rose, widely regarded as the father of autoimmune disease research, dies at 92 - The Hub at Johns Hopkins

IRVINE, Calif., Aug. 4, 2020 /PRNewswire/ --Seragon Pharmaceuticals, Inc. today announced GenomeScore, the first artificial intelligence platform combining epigenetic and transcriptome analyses to predict a person's aging speed and assess different aspects of physiological function.

"How you age depends on how you lived your life up to this point, and GenomeScore looks into what's currently occurring in your body at the molecular level," said Lead Scientist Aake Vaestermark of Seragon Pharmaceuticals. While traditional genetic tests reveal genetic predisposition, the company's new platform allows individuals to understand how well their biological system is performing over time. "Conventional genetic tests are like comparing the cars that haven't been used, but our new platform is like comparing used cars to see if all the components are up and running after all those years."

Unlike existing epigenetic age tests that only provides an overall body age, GenomeScore's neural network-trained algorithms paint a more detailed and complete picture of the body's age in different areas. The platform shows both the individual's biological age and predicts one's body aging rate. By combining transcriptome analysis, an assessment of gene expression, the platform can also predict the "age" of other physiological functions such as the immune and endocrine systems.

"The platform could act like a warning sign if one of your organs is growing old particularly fast," said Dr. Vaestermark. "It can be a way of finding your weakest point physically, and people want to know that."

Traditionally, people estimate their age through chronological years, the number that one celebrates on their birthday each year. However, individuals age in different paces due to factors like genetics and lifestyles. Based on a set of proprietary epigenetic, metabolic and gene expression markers, GenomeScore platform can predict an individual's speed of aging and physiological changes.

GenomeScore provides a novel way of measuring health parameters that may translate to clinical applications for consumers to better predict how lifestyles and other factors impact their process of aging. For scientists and physicians, a better understanding of how individual ages may provide the opportunity to develop personalized medicine to target patients' medical needs in the future.

Through Seragon Pharmaceuticals' dedication to innovation and technology advancement, the company has developed a set of microarray chips based on the GenomeScore algorithms to make the platform more accessible. The technology further expands the company's bioinformatics research and product portfolio, fulfilling its commitment to creating healthier communities through advancing science and product development.

About Seragon PharmaceuticalsSeragon Pharmaceuticals, Inc., headquartered in Irvine, California, is a research-based biopharmaceutical company dedicated to improving human and animal health through innovative science. Seragon Pharmaceuticals is committed to applying cutting-edge scientific and technological advancements to the fields of metabolism, gene therapy and bioinformatics. From the research end to consumer products and clinical applications, Seragon strives to bring people access to the most significant breakthroughs in medicine. For more information, please visit http://www.seragon.com.

Media Contact: Tiffany Chen [emailprotected]

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https://www.seragon.com

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Seragon Announces GenomeScore, the First AI Platform to Measure Rate of Aging and Physiological Changes - PRNewswire

DURHAM, N.C., July 29, 2020 (GLOBE NEWSWIRE) -- Atsena Therapeutics, a clinical-stage gene therapy company focused on bringing the life-changing power of genetic medicine to reverse or prevent blindness, today announced that it has acquired exclusive rights to a gene therapy targeting GUCY2D-associated Leber congenital amaurosis (LCA1), a genetic eye disease that affects the retina and is a leading cause of blindness in children, from Sanofi, which originally licensed it from the University of Florida. The therapy was created in the laboratory of Atsena Founder and Chief Scientific Officer Shannon Boye, Ph.D., and Founder and Chief Technology Officer Sanford Boye, M.Sc., at the University of Florida.

We are thrilled that our gene therapy for LCA1 is coming home to Atsena and that we will have the opportunity to further its development, said Shannon Boye. Atsena was founded to advance treatments for inherited retinal diseases and believes in centering patients perspectives and needs in all we do. We are honored to continue to work with LCA1 patients and their families as we strive to treat this debilitating disease.

LCA is the most common cause of blindness in children, impacting two to three per 100,000. LCA1 is caused by mutations in the GUCY2D gene and results in early and severe vision impairment or blindness. GUCY2D-LCA1 is one of the most common forms of LCA, affecting roughly 20 percent of patients who live with this inherited retinal disease.

Atsena has an ongoing Phase I/II clinical trial evaluating this gene therapy in LCA1 patients. The second cohort in the trial is expected to be dosed in the fall of 2020.

Atsenas gene therapy has the potential to be a major advance in treating blindness in both children and adults affected by this inherited retinal disease, said Benjamin Yerxa, Ph.D., Chief Executive Officer of the Foundation Fighting Blindness and Atsena board director. The foundation was instrumental in supporting proof of concept studies in the founders labs over the last 15 years. Now, via investment in Atsena through our Retinal Degeneration (RD) Fund, we are excited to support this potential breakthrough treatment for LCA1.

Atsena closed a Series 1 funding of $8.15 million in April 2020, led by founding investors Hatteras Venture Partners and the Foundation Fighting Blindness RD Fund with participation by Osage University Partners, PBM Capital and the University of Florida. Patrick Ritschel, M.B.A., co-founder and former President of gene therapy company StrideBio, serves as Atsenas Chief Executive Officer.

Atsena is pleased to have the support of an enthusiastic investor base that shares our dedication to bringing the life-changing power of genetic medicine to patients living with LCA1 and other forms of blindness, said Ritschel. We look forward to working closely with our investors and patients as we continue to grow, and expect to announce additional milestones later this year.

About Atsena Therapeutics

Atsena Therapeutics is a clinical-stage gene therapy company, focused on bringing the life-changing power of genetic medicine to reverse or prevent blindness. The company has an ongoing Phase I/II clinical trial evaluating a potential therapy for one of the most common causes of blindness in children. Its additional pipeline of leading preclinical assets is powered by an adeno-associated virus (AAV) technology platform tailored to overcome the hurdles presented by inherited retinal disease, and its approach is guided by the specific needs of each patient condition. Founded by pioneers in ocular gene therapy, Atsena has a licensing, research and manufacturing collaboration with the University of Florida and is headquartered in North Carolinas Research Triangle, an environment rich in gene therapy expertise. For more information, please visit atsenatx.com.

Media Contact:Tony Plohoros6 Degrees(908) 591-2839tplohoros@6degreespr.com

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Atsena Therapeutics acquires exclusive rights to Gene Therapy for GUCY2D-associated Leber Congenital Amaurosis - GlobeNewswire

As the days unfold with a seeming sameness in this odd summer of the pandemic, news of vaccine clinical trials begins to trickle in, and another buzzword from epidemiology is entering the everyday lexicon: durability.

To be successful, a vaccines protection must last or booster shots periodically restore it. Some vaccines lose efficacy over time, including those for yellow fever, pertussis, and of course influenza.

For some vaccines, antibodies and the B cells that make them persist and protect for a long time. For other infectious diseases, like TB and malaria, T cells are needed in vaccines too. B and T cells (lymphocytes) are types of white blood cells, which are part of the immune system.

Give amanafishand you feedhimfor a day.Teach himhow tofishand you feedhimfor a lifetime, said Chinese philosopher Lao Tzu, founder of Taoism.

Tzu might have been referring metaphorically to the immune systems response to viral infection: an initial rush of antibodies that fades as a longer-lasting cell-based memory builds that primes the body to rapidly release antibodies upon a future encounter with the pathogen.

Antibodies are proteins, so they dont make more of themselves as cells might. Thats why antibodies collected from plasma from a person whos recovered from COVID-19 lasts a few weeks. Its also why an antibody medicine like Regenerons dual-antibody REGN-COV2 provides only short-term protection, a bridge until a vaccine becomes available.

To remain effective over a reasonable period of time, a vaccine must mimic the memory component of an immune response, which arises from B and T cells and is therefore called the cellular immune response. The shorter-term release of antibodies into the bloodstream is the humoral immune response (humor means fluid).

A strong antibody response to a vaccine may be a harbinger of lasting B and T cell protection, but vaccines may be marketed before their durability is known a complete understanding of how long a vaccines protection lasts can take years. The vaccine against the mumps, for example, went on the market in 1967, but in 2006, several colleges had outbreaks, among students whose childhood mumps vaccine had worn off. A booster extends the coverage.

Clues to a COVID-19 vaccines durability come from natural immunity from past coronavirus infections. The antibody response to SARS and MERS persisted less than a year. But so far, the cellular immune response to SARS, the older of the two, has lasted eleven years.

Clinical trials to evaluate COVID-19 vaccines in people consider both antibody production and the building of cellular immunity. And a vaccine can be even more protective than natural immunity.

A vaccine elicits memory B and T cells so the immune system remembers how to fight the disease in the future. Natural infection is not likely to produce durable immunity and vaccination will be essential to produce herd immunity to reduce the probability of viral transmission, said Arlene Sharpe MD PhD co-director of the Evergrande Center for Immunologic Diseases at Harvard Medical School and Brigham and Womens Hospital on a recent zoom that MassCPR, a group of Boston-area institutions that formed in early March in response to the pandemic, held.

The immune system isnt as easy to visualize as a skeleton splayed out in a Halloween decoration, the flattened entrails of a roadkill, or the circulatory system, which even Groucho Marx in the film Horse Feathers could easily explain. (Let us follow a corpuscle on its journey through the body.)

Instead, the immune system is an army of billions of cells and their secretions that stand ready to attack newly encountered pathogens, remember old ones, and at the same time recognize self, protecting the bodys own tissues. The cells travel in clear lymph fluid, passing through lymph nodes that filter out debris.

The immune system reacts in three stages. First, physical barriers keep pathogens out: skin, earwax, waving cilia in the throat, stomach acid, diarrhea. Next, innate immunity unleashes a bath of inflammatory molecules that are a generalized response to infection.

Finally comes adaptive immunity, which is specific and provides the memory that a vaccine emulates. In addition to T and B cells, innate immunity includes the wandering, blobby macrophages, which engulf pathogens and are festooned with bits of a pathogens surface antigens that alert other immune defenses.

Antibody production begins when a stimulated B cell divides in the bone marrow, giving rise to two types of cells. One, a plasma cell, has a clear oblong area that is a ginormous Golgi apparatus, which processes 2,000 antibodies per second that enter the circulation.

The second daughter cell of a dividing B cell is a memory B cell. Like the name suggests, a memory B cell hangs around, and if the pathogen shows up again, jumps into action and pumps out more antibodies, cutting off the new infection fast.

An important part of the antibody response is that its polyclonal differently-shaped antibodies are produced, each recognizing and binding to a different part of a pathogen, like using different weapons to tackle different parts of an enemys body.

Some antibodies just bind to a pathogen, but others neutralize it, and those are the ones that make a vaccine or immune response effective. Yet certain other antibodies actually enhance infection; vaccines are designed to block this from happening.

T cells come in several varieties and exert complex effects.

Tracking T cells is important in evaluating potential vaccine durability. And although we only have a half-year of data, the natural infection suggests that antibody responses may be short-lived or not strong enough.

Investigators are reporting the antibody response in humans infected with COVID who recover tends to drop relatively quickly. To some people thats an alarm bell and they guess that a vaccine will show little durability. But following recovery from an acute infection, a decline in antibodies is normal B cell biology and is exactly what we predict, said Daniel Barouch, MD, PhD, professor of medicine, Harvard Medical School and director, Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center.

One of the first reports showed antibodies decreasing by half in just 37 days among a small sample of people who had mild cases. Thats similar to SARS and MERS, in which antibodies fade away within a year. But so far, reports of phase 1 clinical trial results for two COVID vaccines are encouraging.

The first interim report, published in The New England Journal of MedicineJuly 14, found that all 45 participants who received one of three doses of Modernas mRNA-1273 vaccine made antibodies, more with the higher dose. Binding antibodies appeared by day 15 and neutralizing antibodies after a second dose on day 28. Neutralizing antibodies are a biomarker of vaccine protection for other respiratory viruses, so thats good news.

Responses are comparable to what occurs with natural infection, and perhaps a little higher. Data are encouraging; the strategy elicits immune responses that are targeted against the virus, said Lindsey R. Baden, MD, associate professor of medicine, Harvard Medical School and director of clinical research, Brigham and Womens Hospital. The study used antibodies in plasma from recovered patients as a control for the natural immune response, and the vaccine exceeded that comparison.

Even better news: participants made T cells. Helpers appear first, which pump out a specific soup of cytokines, and then after the second dose of vaccine, killers appear, making sure that any remaining viruses cant replicate.

The phase 1 trial showed that the middle of three doses is best for tempering efficacy with side effects. Phase 2 began in May and phase 3, began on July 27. Overall, depending on the number of trials that progress, hundreds of thousands of people may participate.

Modernas vaccine (mRNA-1273) is designed to enhance visibility to the immune system. The target cell translates it into an engineered version of the viruss spike protein that tames the inflammatory response. The spike is also tweaked to be more stable than the natural one.

On July 20 the second clinical trial report came from the Oxford COVID Vaccine Trial Groups candidate ChAdOx1, in The Lancet. That vaccine consists of the genetic instructions for the spike protein delivered in a chimpanzee virus.

Like the mRNA vaccine, Oxfords candidate is given in doses 28 days apart. And it, too, evokes both a humoral (antibody) and cellular (T cell) response.

So far, the numbers of vaccinated people are small, but the reports are optimistic.

With clever variationson the clinical trial theme, like overlapping phases and designing spike proteins to be more visible to the immune system, it may indeed be possible to barrel through phase 3 clinical trials that test a statistically significant number of people. But post-marketing surveillance, a normal part of drug development, is going to be critical.

The participants in the MassCPR zoom marveled that vaccine development for COVID-19 is so far taking 5 to 10 months, compared to the historical 5 to 10 years.

We are only months into knowing about this virus, so any longevity of the immune response we have to interpret with care because our understanding of the biology and durability of the biology will take time. The virus will evolve and we have to take that into consideration, said Baden. He showed data from monkeys that suggest a long-lasting effect is possible.

Practically speaking, the phase 3 trials will take time because the participants arent being injected with virus, for ethical reasons. Instead, investigators must wait for the volunteers to encounter the virus in their communities, to see if a smaller percentage of vaccinated people become infected than the unvaccinated control groups. And thats why a vaccine by the end of the year would be quite a surprise for many of us, said Ken Mayer, MD, of the Fenway Institute.

Well have increasing clarity as the next 3 to 6 months proceed with a suite of clinical trials underway or soon to be. Most optimistic is late fall for first availability for an Emergency Use Authorization. But a tremendous number of things would have to go perfectly to achieve that. Early 2021 is more realistic, said Barouch. An EUA brought COVID-19 treatment remdesivir to patients before the official FDA approval.

Baden agreed that early 2021 is more feasible. He points out the potential savings of 6 to 12 months from beginning to manufacture candidate vaccines before their clinical trials conclude, well before. Financial risks are acceptable, safety not, and thats why it will take at least 3 to 6 months more.

Once a vaccine is out there, attention will turn to epidemiology. What percentage of the population must be vaccinated or have natural immunity to induce herd immunity? And how many people will actually take a vaccine?

If several vaccines make it to the finish line, how will people be assigned to them? People over age 65, for example, would benefit most from a vaccine that includes an adjuvant, which is a chemical that affects the immune response. A vaccine candidate from Australian biotech company Vaxine Pty Limited, for example, includes a complex sugar that lowers the risk of the vaccine triggering an excessive immune response. The sugar adjuvant has worked well in vaccines against influenza, hepatitis B, and West Nile virus, according to Nikolai Petrovsky, PhD, research director at the company.

Assessing the all-important T cell response will take time, too, because thats the way the cellular immune response unfurls in nature. Gradually. A full immune response is a finely-tuned process that is a consequence of millennia of evolution not of politics, PR, potential profits, or wishful thinking.

Ricki Lewis has a PhD in genetics and is a genetics counselor, science writer and author of Human Genetics: The Basics. Follow her at her website or Twitter @rickilewis.

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Vaccine 'durability': COVID-19 immunizations coming soon but will they last? - Genetic Literacy Project

CINCINNATI, Aug. 04, 2020 (GLOBE NEWSWIRE) -- Aerpio Pharmaceuticals, Inc. (Aerpio) (Nasdaq: ARPO) and The U.S. Government operating through the Medical Technology Enterprise Consortium (MTEC) announced today that an agreement has been reached to evaluate razuprotafib in a new randomized, investigational trial for the prevention and treatment of Acute Respiratory Distress Syndrome (ARDS) in adult patients with moderate to severe COVID-19 as part of MTEC-20-09-COVID-19 Treatment Military Infectious Disease Research Program (MIDRP) Development of Treatments for COVID-19. MTEC will provide up to $5.1 million in funding toward the clinical trial. Aerpio will support the trial with in kind spending in the amount of $2.8 million. MTEC is a 501(c)3 non-profit organization constructed by the U.S. Army Medical Research and Development Command (USAMRDC). The Medical Technology Enterprise Consortium (MTEC) was established as an enterprise partnership including industry and academia to facilitate research and development activities. Protecting U.S. forces from COVID-19 is a key priority for the U.S. military. The partnership between Aerpio and MTEC will provide resources to support a second COVID-19 Phase 2 clinical trial with razuprotafib, a drug candidate being investigated for its potential to prevent and treat the severe respiratory distress observed in COVID-19 patients.

Aerpio Pharmaceuticals is developing a potent and selective small molecule inhibitor of vascular endothelial protein tyrosine phosphatase (VE-PTP), razuprotafib (AKB-9778), that restores Tie2 pathway activation in endothelial cells to stabilize blood vessels during vascular injury and inflammation. Emerging data indicate that SARS-Cov2, the virus that causes COVID-19, may attack vascular endothelium and destabilize blood vessels in multiple organs including the lung, kidneys and heart leading to substantial morbidity and mortality. Based on these findings, Aerpio and a distinguished team of clinical investigators have developed a plan to investigate the therapeutic potential of subcutaneous razuprotafib for the prevention and treatment of ARDS in patients with moderate to severe COVID-19.

Wesley H. Self, MD, MPH Associate Professor and Vice Chair for Research in the Department of Emergency Medicine at Vanderbilt University Medical Center and Aerpio COVID-19 Steering Committee stated, A Tie2 activator that can be administered without an IV to stabilize the pulmonary vasculature would be a breakthrough for reducing the devastating effects of COVID19 associated pulmonary pathology. This therapeutic could result in fewer COVID-19 patients requiring mechanical ventilation, earlier recovery with decreased time in the hospital and ICU and an overall reduction in morbidity and mortality.

Jeff Sabados MPP MBA, member of Aerpios COVID-19 Steering Committee, who served for 20 years in both Active and Reserve Duty in the U.S. Navy, commented, The subcutaneous administration of razuprotafib to activate Tie2 makes this particularly attractive to active duty military personnel around the globe because razuprotafib has the potential to save lives in the next pandemic and return soldiers back to the front lines. I am very proud to be a part of this effort.

About the MTEC TrialWe hypothesize that razuprotafib, a first-in-class Tie2 activating compound, will exhibit an acceptable safety profile and show efficacy for treatment of ARDS in patients with moderate to severe COVID-19 and be a life-saving therapeutic for service members in the field suffering from the devasting respiratory and vascular effects of COVID-19. Aerpio, through the support of MTEC will conduct a Phase 2 clinical trial of subcutaneous razuprotafib for the treatment of patients with moderate to severe COVID-19. The Phase 2 trial will be conducted at approximately 10 clinical sites and is expected to be completed in the first quarter of 2021.

About MTECThe Medical Technology Enterprise Consortium (MTEC) is a 501(c)(3) biomedical technology consortium collaborating under an Other Transaction Agreement (OTA) with the U.S. Army Medical Research and Development Command (USAMRDC) that serves those who serve our nation.

About Razuprotafib (previously AKB-9778)Razuprotafib binds to and inhibits vascular endothelial protein tyrosine phosphatase (VE-PTP), an important negative regulator of Tie2. Decreased Tie2 activity contributes to vascular instability in many diseases including diabetes. Razuprotafib activates the Tie2 receptor irrespective of extracellular levels of its binding ligands, angiopoietin-1 (agonist) or angiopoietin-2 (antagonist) and may be the most efficient pharmacologic approach to maintain normal Tie2 activation. As seen preclinically, activation of Tie2 by razuprotafib stabilizes vasculature which may have beneficial effects in a variety of disease states, including COVID-19.

About Aerpio PharmaceuticalsAerpio Pharmaceuticals, Inc. is a biopharmaceutical company focused on developing compounds that activate Tie2 to treat ocular diseases and diabetic complications. Recently published mouse and human genetic data implicate the Angpt/Tie2 pathway in maintenance of Schlemms canal, a critical component of the conventional outflow tract. The Companys lead compound, razuprotafib (formerly AKB-9778), a first-in-class small molecule inhibitor of vascular endothelial protein tyrosine phosphatase (VE-PTP), is being developed as a potential treatment for open angle glaucoma, and the Company intends to investigate the therapeutic potential of razuprotafib in other indications. The Company is also evaluating development options for ARP-1536, a humanized monoclonal antibody, for its therapeutic potential in the treatment of diabetic vascular complications including nephropathy and diabetic macular edema (DME). The Companys third asset is a bispecific antibody that binds both VEGF and VE-PTP which is designed to inhibit VEGF activation and activate Tie2. This bispecific antibody has the potential to be an improved treatment for wet age-related macular degeneration and DME via intravitreal injection. Finally, the Company has exclusively out-licensed AKB-4924 (now called GB004), a first-in-class small molecule inhibitor of hypoxia-inducible factor-1 (HIF). GB004 is being developed by AKB-4924s exclusive licensor, Gossamer Bio, Inc. (Nasdaq: GOSS). For more information, please visit http://www.aerpio.com.

Forward Looking StatementsThis press release contains forward-looking statements. Statements in this press release that are not purely historical are forward-looking statements. Such forward-looking statements include, among other things, the Companys product candidates, including razuprotafib, ARP-1536 and the bispecific antibody asset, the clinical development plan therefor and the therapeutic potential thereof, the Companys plans and expectations with respect to razuprotafib and the development therefor and therapeutic potential thereof in addressing COVID-19 and the intended benefits from the Companys collaboration with Gossamer Bio for GB004, including the continued development of GB004 and the milestone and royalty payments related to the collaboration. Actual results could differ from those projected in any forward-looking statements due to several risk factors. Such factors include, among others, the continued development of GB004 and maintaining and deriving the intended benefits of the Companys collaboration with Gossamer Bio; ability to continue to develop razuprotafib or other product candidates, including in indications related to COVID-19; the inherent uncertainties associated with the drug development process, including uncertainties in regulatory interactions, the design of planned or future clinical trials, commencing clinical trials and enrollment of patients in clinical trials; obtaining any necessary regulatory clearances in order to commence and conduct planned or future clinical trials; the impact of the ongoing COVID-19 pandemic on the Companys business operations, including research and development efforts and the ability of the Company to commence, conduct and complete its planned clinical activities; and competition in the industry in which the Company operates and overall market conditions; and the additional factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2019, as updated by our subsequent Quarterly Reports on Form 10-Q and our other subsequent filings with the SEC.

These forward-looking statements are made as of the date of this press release, and the Company assumes no obligation to update the forward-looking statements, or to update the reasons why actual results could differ from those projected in the forward-looking statements, except as required by law. Investors should consult all the information set forth herein and should also refer to the risk factor disclosure set forth in the reports and other documents the Company files with the SEC available at http://www.sec.gov.

Contacts for Aerpio Pharmaceuticals, Inc:Investors & Media:

Gina MarekVP Financegmarek@aerpio.comOrInvestors:Irina KofflerLifeSci Advisorsikoffler@lifesciadvisors.com

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Aerpio Pharmaceuticals, Inc. Announces a Second Clinical Trial with Funding from MTEC to Evaluate Razuprotafib for the Prevention and Treatment of...

BEDFORD, Mass.--(BUSINESS WIRE)--Stoke Therapeutics, Inc., (Nasdaq: STOK), a biotechnology company pioneering a new way to treat the underlying cause of genetic diseases by precisely upregulating protein expression, today announced that members of management will present at three upcoming investor conferences in August:

2020 Wedbush PacGrow Healthcare Virtual ConferenceDate: Tuesday, August 11, 2020Time: 11:30 a.m. ET

BTIG Virtual Biotechnology ConferenceDate: Tuesday, August 11, 2020Time: 2:00 p.m. ET

Canaccord Genuity 40th Annual Growth ConferenceDate: Wednesday, August 12, 2020Time: 2:30 p.m. ET

A live audio webcast of each presentation will be available on the Investors & Media section of Stokes website at https://investor.stoketherapeutics.com/. A replay of the webcasts will be available for 30 days following the presentations.

About Stoke Therapeutics

Stoke Therapeutics, Inc. (Nasdaq: STOK), is a biotechnology company pioneering a new way to treat the underlying causes of severe genetic diseases by precisely upregulating protein expression to restore target proteins to near normal levels. Stoke aims to develop the first precision medicine platform to target the underlying cause of a broad spectrum of genetic diseases in which the patient has one healthy copy of a gene and one mutated copy that fails to produce a protein essential to health. These diseases, in which loss of approximately 50% of normal protein expression causes disease, are called autosomal dominant haploinsufficiencies. The companys lead investigational new medicine is STK-001, a proprietary antisense oligonucleotide (ASO) that has the potential to be the first disease-modifying therapy to address the genetic cause of Dravet syndrome, a severe and progressive genetic epilepsy. Stoke is headquartered in Bedford, Massachusetts with offices in Cambridge, Massachusetts. For more information, visit https://www.stoketherapeutics.com/ or follow the company on Twitter at @StokeTx.

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Stoke Therapeutics to Present at Upcoming Investor Conferences in August - Business Wire

New York, Aug. 04, 2020 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "Cell & Gene Therapy Market - Global Outlook and Forecast 2020-2025" - https://www.reportlinker.com/p05827567/?utm_source=GNW 90% during the period 20192025.

The global cell and gene therapy market is one of the fastest-growing segments in the regenerative medicine market. The market is expected to grow at a faster pace during the forecast period. The demand can be attributed to the growing prevalence of several chronic diseases such as cancer, cartilage related problems, wounds, diabetic foot ulcer, genetic disorders, and other rare diseases across the globe. The prevalence of cancer and diabetes is increasing in the global population, which is influencing the growth of the market. There is a large unmet need in the treatment available, which is filled by cell and gene therapies. The market is growing due to the increased availability of funding from various public and private institutions. Besides, there is increased support from regulatory bodies for product approval. Several governments are creating awareness of cell and gene therapies in the population.

The following factors are likely to contribute to the growth of the cell and gene therapy market during the forecast period: Increase in Strategic Acquisition Activities Increased Funding for Cell & Gene Therapy Products Expanding Applications of Cell and Gene Therapies Increased in the Patient Pool

The study considers the present scenario of the cell and gene therapy market and its market dynamics for the period 2019?2025. It covers a detailed overview of several market growth enablers, restraints, and trends. The report offers both the demand and supply aspects of the market. It profiles and examines leading companies and other prominent ones operating in the market. Cell And Gene Therapy Market Segmentation The global cell and gene therapy market research report includes a detailed segmentation by product, disease, end-user, and geography. In 2019, the cell therapy segment accounted for a market share of over 53% in the global cell and gene therapy market. The segment is expected to grow at a steady rate during the forecast period due to the increase in the target population and the rise in the number of countries preferring cell therapies in their patients. Increased therapeutic benefits are attracting several countries to invest in this technology and conduct a high number of clinical trials. However, the lack of advanced infrastructure in developing countries is hindering the growth of the segment.

In 2019, the oncology segment accounted for a share of over 40% in the global cell and gene therapy market. Oncology has been one of the targets of intense research for the gene therapy procedures & approach. More than 60% of on-going gene therapy clinical trials are targeting cancer. The segment is expected to grow at a promising rate on account of the high prevalence of cancer diseases, especially in low and middle-come countries. The market is growing at a double-digit CAGR, which is expected to help the segment as many cell and gene therapy for cancer are commercially available.

The dermatology application segment in the cell and gene therapy includes wound care management among patients. Vendors are focusing on the development and commercialization of advanced wound care products for the treatment of chronic and acute wounds, thereby increasing the growth of the wound care market. The increased pervasiveness of diabetics is increasing acute and chronic wounds, including surgical wounds, pressure ulcers, diabetic foot ulcers, and other wounds.

In 2019, the oncology segment accounted for a share of over 40% in the global cell and gene therapy market. Oncology has been one of the targets of intense research for the gene therapy procedures & approach. More than 60% of on-going gene therapy clinical trials are targeting cancer. The segment is expected to grow at a promising rate on account of the high prevalence of cancer diseases, especially in low and middle-come countries. The market is growing at a double-digit CAGR, which is expected to help the segment as many cell and gene therapy for cancer are commercially available.

The dermatology application segment in the cell and gene therapy includes wound care management among patients. Vendors are focusing on the development and commercialization of advanced wound care products for the treatment of chronic and acute wounds, thereby increasing the growth of the wound care market. The increased pervasiveness of diabetics is increasing acute and chronic wounds, including surgical wounds, pressure ulcers, diabetic foot ulcers, and other wounds.

Segmentation by Product Cell Therapy Gene Therapy Segmentation by Disease Dermatology Musculoskeletal Oncology Genetic Disorders Others Segmentation by End-user Hospitality Cancer Care Centers Wound Care Centers Ambulatory Surgical Centers Others

INSIGHTS BY GEOGRAPHY In 2019, North America accounted for a share of over 60% of the global cell and gene therapy market. There are more than 530 regenerative medicine companies, including cell and gene therapy manufacturing developers. The number of products approved in North America grew significantly in 2019, with developers filed for marketing authorization for 10+ regenerative medicines, many of which we expect to be approved in 2020. Within the next 12 years, the number of approved gene therapies is expected to double. The US and Canada are the major contributors to the cell and gene therapy market in North America. Regulatory bodies are supporting several investigational products, fast track approvals, RMAT designation for the faster approval of the product into the market. The alliance for regenerative medicine and Medicare and Medicaid is working together to bring the structured reimbursement channels for cell and gene therapies.

Segmentation by Geography North America o US o Canada Europe o UK o Germany o France o Spain o Italy APAC o China o Japan o South Korea o Australia o India Latin America o Brazil o Mexico Middle East & Africa o Saudi Arabia o Turkey o South Africa o UAE

INSIGHTS BY VENDORS The global cell and gene therapy market is highly dynamic and characterized by the presence of several global, regional, and local vendors offering a wide range of therapies. Dendreon, Gilead Sciences, Novartis, Organogenesis, Osiris Therapeutics, Vericel, Amgen, and Spark Therapeutics are the leading players in the market with significant shares. Vendors such as NuVasive, APAC Biotech, Nipro, Orthocell, bluebird bio, J-TEC, and Terumo are the other prominent players in the market with a presence, especially in the cell therapy market. Most leading players are focusing on implementing strategies such as product launches and approvals, marketing and promotional activities, acquisitions, increased R&D investments, and strengthening their distribution networks to enhance their share and presence in the market.

Prominent Vendors Gilead Sciences Spark Therapeutics Novartis Organogenesis Amgen Osiris Therapeutics Dendreon Vericel

Other Prominent Vendors Anterogen Tego Sciences Japan Tissue Engineering JCR Pharmaceuticals Medipost MolMed AVITA Medical CollPlant Biosolution Stempeutics Research Kolon Tissue Gene Orchard Therapeutics Sibiono GeneTech NuVasive Corestem Pharmicell Shanghai Sunway Biotech RMS Regenerative Medical System Takeda Pharmaceutical Company CHIESI Farmaceutici CO.DON AnGes GC Pharma Human Stem Cells Institute JW CreaGene APAC Biotech Nipro Terumo Orthocell bluebird bio

Key Questions Answered 1. What is the cell and gene therapy market size and growth rate during the forecast period? 2. What are the factors impacting the growth of the cell and gene therapy market share? 3. How is the growth of the healthcare segment affecting the growth of the cell and gene therapy market? 4. Who are the leading vendors in the cell and gene therapy market, and what are their market shares? 5. Which product type/ end-user type/region is generating the largest revenue in the Asia Pacific region?Read the full report: https://www.reportlinker.com/p05827567/?utm_source=GNW

About ReportlinkerReportLinker is an award-winning market research solution. Reportlinker finds and organizes the latest industry data so you get all the market research you need - instantly, in one place.

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The global cell and gene therapy market by revenue is expected to grow at a CAGR of over 30.90% during the period 20192025 - GlobeNewswire

04Aug2020

University of Gttingen device points towards more efficient treatments.

Cochlear implants are an established treatment, using a microphone to detect sound and converting that sound into electrical impulses, split into several channels for different frequency ranges. Electrode contacts, typically 12 to 24 in number, then deliver the electrical impulses to the ganglion neurons of the cochlea.

But these devices can offer poor quality sound encoding, partly due to the large lateral spread of electrical current from each electrode, stimulating too many auditory neurons at the same time. A project at the University of Gttingen has now developed a light-based alternative device, reported in Science Translational Medicine.

"The lateral spread is considered the major bottleneck of electrical implants," said Tobias Moser of the University of Gttingnen. "Despite efforts such as multipolar stimulation and current steering, it seems hard or even impossible to overcome."

Neurons are not typically light sensitive, although the growing field of optogenetics has found elegant ways to induce neurons into expressing light-sensitive proteins through genetic modifications in so-called transgenic animals, and making the neurons react to illumination by laser pulse.

Since light can be better confined in space than electric current, optogenetic techniques could allow cochlea stimulation to be made more efficient. However, light sources for optogenetics have usually been individual GaN-based LEDs and optical fibers coupled to external lasers.

In designing an optical cochlear implant (oCI) for auditory treatment and future clinical translation, the Gttingen project had to develop multichannel devices suitable for this very specific purpose.

The eventual design featured a linear array of 10 LED chips, each 270 by 220 microns and emitting at 457 nanometers, integrated onto microfabricated 15-micron-thick polyimide-based carriers with interconnecting lines to address individual LEDs.

Hearing restored

"The linear array of 10 LEDs at the oCI tip was designed with a pitch of 500 or 350 microns," noted the project in its published paper. "In addition, an array with four LEDs containing a temperature sensor integrated beneath the first LED chip enables a precise resistance measurement, and thus allows monitoring of potential temperature increase inside the implant."

Having optimized the design for rodent ears, the project inserted the device into transgenic rats and characterized the oCI's stimulation of the animals' auditory nerves. Comparing the spatial spread of excitation from the LEDs of the oCI to that from electrodes of a conventional electrical implant by monitoring the animal's midbrain allowed the frequency selectivity of the oCI device to be characterized.

In behavioral experiments, the team began with rats with normal hearing and trained them to perform a behavior driven by sound. After deafening the rats, the team implanted the oCI device and found that the animals could still perform the acoustically trained behavior with the aid of the multichannel implant.

According to the project, results showed that use of gene therapy and the optical implant in conjunction led to an improved frequency selectivity compared with the electrical alternative, and future enhancements to both the size of LEDs and the spread of light from each emitter could enhance this parameter further.

Although further work will be needed before clinical trails using the device can start, including more detailed studies of behavioral analysis connected with the technique, the team has founded a spin-out company, OptoGenTech, to potentially assist translation of the gene therapy and oCI combination into a human clinical trial and, eventually, bring it to market.

"This is the first demonstration and characterization of preclinical hearing restoration by a complete multichannel oCI system based on LEDs," commented Moser.

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Cochlear implant uses LEDs to tackle hearing loss - Optics.org

DetailsCategory: Small MoleculesPublished on Monday, 03 August 2020 13:50Hits: 870

BASEL, Switzerland I August 03, 2020 I Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the European Commission has granted conditional marketing authorisation for Rozlytrek (entrectinib) for the treatment of adult and paediatric patients 12 years of age and older with solid tumours expressing a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, who have a disease that is locally advanced, metastatic or where surgical resection is likely to result in severe morbidity, and who have not received a prior NTRK inhibitor, who have no satisfactory treatment options. The European Commission has also approved Rozlytrek for the treatment of adults with ROS1-positive, advanced non-small cell lung cancer (NSCLC) not previously treated with ROS1 inhibitors.1

We are excited to announce the approval of Rozlytrek in Europe for two indications, bringing patients with NTRK and ROS1 gene fusions a new effective treatment even when their cancer has spread to the brain, said Levi Garraway, M.D., Ph.D., Roches Chief Medical Officer and Head of Global Product Development. This advance represents another important step forward in cancer care by allowing us to treat certain genetic drivers of cancer irrespective of the location of the tumour within the body. Roche is deeply committed to driving personalised healthcare and addressing the high unmet need in patients around the world with rare cancers.

The approval is based on results from the integrated analysis of the pivotal phase II STARTRK-2, phase I STARTRK-1 and phase I ALKA-372-001 trials, and data from the phase I/II STARTRK-NG study. These studies demonstrate that Rozlytrek has durable responses across several NTRK gene fusion-positive solid tumours, including sarcoma, non-small cell lung, salivary MASC, secretory and non-secretory breast, thyroid, colorectal, neuroendocrine, pancreatic, ovarian, endometrial carcinoma, cholangiocarcinoma, gastrointestinal cancers and neuroblastoma, as well as ROS1-positive NSCLC.1 Results showed:

Rozlytrek has been granted Priority Medicines (PRIME) designation by the EMA for the treatment of NTRK fusion-positive, locally advanced or metastatic solid tumours in adult and paediatric patients who have either progressed following prior therapies or who have no acceptable standard therapies.1 NTRK gene fusions have been identified in a range of solid tumour types, and are present in up to 90% of some rare cancer types and less than 1% of other more common tumours, including lung and colorectal.2 ROS1 gene fusions account for 1-2% of NSCLC, the most common type of lung cancer that accounts for up to 85% of all diagnoses.3,4

Biomarker testing for these fusions is the most effective way to identify people who are most eligible for treatment with Rozlytrek. Roche is leveraging its expertise in developing personalised medicines and advanced diagnostics, in conjunction with Foundation Medicine, to develop a companion diagnostic that will help identify people with NTRK and ROS1 gene fusions.

About the integrated analysisThe approval in Europe is based on an integrated analysis including data from 74 people with locally advanced or metastatic NTRK fusion-positive solid tumours (14 tumour types) and 161 people with ROS1-positive NSCLC from the phase II STARTRK-2, phase I STARTRK-1 and phase I ALKA-372-001 trials.1 It is also based on data from the phase I/II STARTRK-NG study in paediatric patients. The studies enrolled people across 15 countries and more than 150 clinical trial sites. Safety was assessed from an integrated analysis of 504 people across these four trials.1

About NTRK fusion-positive cancer NTRK fusion-positive cancer occurs when the NTRK1/2/3 genes fuse with other genes, resulting in altered TRK proteins (TRKA/TRKB/TRKC) that can activate signalling pathways involved in the proliferation of certain types of cancer.5 NTRK gene fusions are present in tumours irrespective of site of origin. These fusions have been identified in a broad range of solid tumour types, including sarcoma, non-small cell lung, salivary MASC, secretory and non-secretory breast, thyroid, colorectal, neuroendocrine, pancreatic, ovarian, endometrial carcinoma, cholangiocarcinoma, gastrointestinal cancers and neuroblastoma.1

About ROS1-positive NSCLCROS1 is a tyrosine kinase, which plays a role in controlling how cells grow and proliferate. When a ROS1 gene fusion occurs, cancer cells grow and proliferate in an uncontrolled manner. Blocking this abnormal signalling can cause tumour cells to shrink or die.3ROS1 gene fusions account for 1-2% of NSCLC.3 Lung cancer is the leading cause of cancer-related death across the world.6 Each year, more than one and a half million people die as a result of the disease globally, equating to more than 4,000 deaths every day.6 NSCLC is the most common type of lung cancer and accounts for up to 85% of all lung cancer diagnoses.4 While the ROS1 gene fusion can be found in any patient with NSCLC, young never-smokers with NSCLC have the highest incidence of ROS1 gene fusions.3

About RozlytrekRozlytrek (entrectinib) is a tumour-agnostic once-daily oral medicine for the treatment of locally advanced or metastatic solid tumours that harbour NTRK1/2/3 or ROS1 gene fusions. It is a selective tyrosine kinase inhibitor designed to inhibit the kinase activity of the TRKA/B/C and ROS1 proteins, whose activating fusions drive proliferation in certain types of cancer.7,8 Rozlytrek can block NTRK and ROS1 kinase activity and may result in the death of cancer cells with NTRK or ROS1 gene fusions.7,8

Rozlytrek was granted accelerated approval in August 2019 by the US Food and Drug Administration (FDA), following receipt of Breakthrough Therapy designation, for the treatment of adult and paediatric patients 12 years of age and older with solid tumours that have a NTRK gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory alternative therapy, and was approved for the treatment of adults with ROS1-positive, metastatic NSCLC. In June 2019, Japans Ministry of Health, Labour and Welfare (MHLW) also approved Rozlytrek for the treatment of adult and paediatric patients with NTRK fusion-positive, advanced recurrent solid tumours, and later approved Rozlytrek in ROS1-positive NSCLC in February 2020. Rozlytrek has also received approvals by health authorities in Australia, Canada, Hong Kong, Israel, New Zealand, South Korea and Taiwan.

About Roche in lung cancerLung cancer is a major area of focus and investment for Roche, and we are committed to developing new approaches, medicines and tests that can help people with this deadly disease. Our goal is to provide an effective treatment option for every person diagnosed with lung cancer. We currently have five approved medicines to treat certain kinds of lung cancer and more than ten medicines being developed to target the most common genetic drivers of lung cancer or to boost the immune system to combat the disease.

About RocheRoche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve peoples lives. The combined strengths of pharmaceuticals and diagnostics under one roof have made Roche the leader in personalised healthcare a strategy that aims to fit the right treatment to each patient in the best way possible.

Roche is the worlds largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management.

Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. The company also aims to improve patient access to medical innovations by working with all relevant stakeholders. More than thirty medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines. Moreover, for the eleventh consecutive year, Roche has been recognised as one of the most sustainable companies in the Pharmaceuticals Industry by the Dow Jones Sustainability Indices (DJSI).

The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2019 employed about 98,000 people worldwide. In 2019, Roche invested CHF 11.7 billion in R&D and posted sales of CHF 61.5 billion. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit http://www.roche.com.

All trademarks used or mentioned in this release are protected by law.

References[1] F. Hoffmann-La Roche Ltd. Data on file.[2] Cocco, E, et al. NTRK fusion-positive cancers and TRK inhibitor therapy. Nat Rev Clin Oncol. 2018; 15:731747[3] Bergethon K, Shaw AT, Ou SH, et al. ROS1 rearrangements define a unique molecular class of lung cancers. J Clin Oncol. 2012; 30(8):863-70.[4] American Cancer Society. What is Non-small Cell Lung Cancer? [Internet; cited 2020 July 8]. Available from: https://www.cancer.org/cancer/lung-cancer/about/what-is.html%5B5%5D Amatu A, Sartore-Bianchi A, Siena S. NTRK gene fusions as novel targets of cancer therapy across multiple tumour types. ESMO Open. 2016;1(2):e000023.[6] GLOBOCAN. Lung Cancer. [Internet; cited 2020 July 8]. Available from: http://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf%5B7%5D Ahn M-J, Cho BC, Siena S, et al. Entrectinib in patients with locally advanced or metastatic ROS1 fusion-positive non-small cell lung cancer (NSCLC). Presented at: IASLC 18th World Conference on Lung Cancer; October 15-18, 2017; Yokohama, Japan. Abstract 8564.[8] Rolfo C, et al. Entrectinib: a potent new TRK, ROS1, and ALK inhibitor. Expert Opin Investig Drugs. 2015;24(11):1493-500.

SOURCE: Roche

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Rozlytrek, Roche's first tumour-agnostic therapy, approved in Europe for people with NTRK fusion-positive solid tumours and for people with...

CAMBRIDGE - Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, announced today that the Company has submitted a clinical trial authorization (CTA) application to The Medicines and Healthcare Products Regulatory Agency (MHRA) in the United Kingdom to initiate a Phase 1 study of ALN-HSD, an investigational RNAi therapeutic targeting HSD17B13 for the treatment of nonalcoholic steatohepatitis (NASH).

The Company plans to initiate a Phase 1 study in late 2020, upon obtaining MHRA approval.

'We are excited to advance our ALN-HSD program to the clinic in partnership with Regeneron, particularly given the mass prevalence and high unmet need in NASH, a progressive disease associated with high morbidity and mortality. Given the genetic validation of the target, we believe ALN-HSD has the potential to change the course of this serious and potentially life-threatening disease for which there are currently no approved pharmacologic treatment options,' said David Erbe, Ph.D., Senior Distinguished Investigator, Program Leader, ALN-HSD program at Alnylam. 'Pending feedback from the MHRA, we look forward to initiating the Phase 1 study to evaluate the safety and preliminary pharmacodynamic activity of ALN-HSD in healthy volunteers and patients with NASH.'

About ALN-HSD

ALN-HSD is an investigational, subcutaneously administered RNAi therapeutic targeting HSD17B13 in development in collaboration with Regeneron Pharmaceuticals for the treatment of nonalcoholic steatohepatitis. ALN-HSD utilizes Alnylam's Enhanced Stabilization Chemistry Plus (ESC+) GalNAc-conjugate technology, which enables subcutaneous dosing with increased selectivity and a wide therapeutic index. The safety and efficacy of ALN-HSD have not been evaluated by the FDA, EMA or any other health authority.

About NASH

Nonalcoholic steatohepatitis (NASH) is a highly prevalent chronic liver disease in which inflammation and liver cell injury are caused by accumulation of hepatic fat. NASH is a subset of a group of conditions called nonalcoholic fatty liver disease (NAFLD) that can lead to progressive fibrosis, cirrhosis, and hepatocellular carcinoma. Comorbidities include obesity, metabolic syndrome, and type 2 diabetes. Approximately 16 million people in the US live with NASH, with prevalence of the disease increasing due to rising rates of obesity. NASH is projected to be the leading indication for liver transplants in developed countries within the next 10 years. There are currently no approved medical therapies for NASH.

About RNAi

RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as 'a major scientific breakthrough that happens once every decade or so,' and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines, known as RNAi therapeutics, is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, function upstream of today's medicines by potently silencing messenger RNA (mRNA) the genetic precursors that encode for disease-causing or disease pathway proteins, thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases.

About Alnylam Pharmaceuticals

Alnylam (Nasdaq: ALNY) is leading the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of people afflicted with rare genetic, cardio-metabolic, hepatic infectious, and central nervous system (CNS)/ocular diseases. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach for the treatment of a wide range of severe and debilitating diseases. Founded in 2002, Alnylam is delivering on a bold vision to turn scientific possibility into reality, with a robust RNAi therapeutics platform. Alnylam's commercial RNAi therapeutic products are ONPATTRO (patisiran), approved in the U.S., EU, Canada, Japan, Brazil, and Switzerland, and GIVLAARI (givosiran), approved in the U.S., EU, and Brazil. Alnylam has a deep pipeline of investigational medicines, including six product candidates that are in late-stage development. Alnylam is executing on its 'Alnylam 2020' strategy of building a multi-product, commercial-stage biopharmaceutical company with a sustainable pipeline of RNAi-based medicines to address the needs of patients who have limited or inadequate treatment options. Alnylam is headquartered in Cambridge, MA.

Alnylam Forward-Looking Statements

Various statements in this release concerning Alnylam's future expectations, plans and prospects, including, without limitation, the potential of investigational RNAi therapeutics, in particular ALN-HSD, Alnylam's filing of a CTA for ALN-HSD and its expectations regarding the anticipated timing for initiation of a Phase 1 study of ALN-HSD, and expectations regarding the continued execution on its 'Alnylam 2020' guidance for the advancement and commercialization of RNAi therapeutics, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results and future plans may differ materially from those indicated by these forward-looking statements as a result of various important risks, uncertainties and other factors, including, without limitation: the direct or indirect impact of the COVID-19 global pandemic or a future pandemic, such as the scope and duration of the outbreak, government actions and restrictive measures implemented in response, material delays in diagnoses of rare diseases, initiation or continuation of treatment for diseases addressed by Alnylam products, or in patient enrollment in clinical trials, potential supply chain disruptions, and other potential impacts to Alnylam's business, the effectiveness or timeliness of steps taken by Alnylam to mitigate the impact of the pandemic, and Alnylam's ability to execute business continuity plans to address disruptions caused by the COVID-19 or a future pandemic; Alnylam's ability to discover and develop novel drug candidates and delivery approaches and successfully demonstrate the efficacy and safety of its product candidates; the pre-clinical and clinical results for its product candidates, which may not be replicated or continue to occur in other subjects or in additional studies or otherwise support further development of product candidates for a specified indication or at all; actions or advice of regulatory agencies, which may affect the design, initiation, timing, continuation and/or progress of clinical trials or result in the need for additional pre-clinical and/or clinical testing; delays, interruptions or failures in the manufacture and supply of its product candidates, including ALN-HSD, or its marketed products; obtaining, maintaining and protecting intellectual property; intellectual property matters including potential patent litigation relating to its platform, products or product candidates; obtaining regulatory approval for its product candidates, including ALN-HSD, and maintaining regulatory approval and obtaining pricing and reimbursement for its products, including ONPATTRO and GIVLAARI; progress in continuing to establish a commercial and ex-United States infrastructure; successfully launching, marketing and selling its approved products globally, including ONPATTRO and GIVLAARI, and achieving net product revenues for ONPATTRO within its revised expected range during 2020; Alnylam's ability to successfully expand the indication for ONPATTRO in the future; competition from others using technology similar to Alnylam's and others developing products for similar uses; Alnylam's ability to manage its growth and operating expenses within the ranges of guidance provided by Alnylam through the implementation of further discipline in operations to moderate spend and its ability to achieve a self-sustainable financial profile in the future without the need for future equity financing; Alnylam's ability to establish and maintain strategic business alliances and new business initiatives, including completing an agreement for funding by Blackstone of certain R&D activities for vutrisiran and ALN-AGT; Alnylam's dependence on third parties, including Regeneron, for development, manufacture and distribution of certain products, including eye and CNS products, Ironwood, for assistance with the education about and promotion of GIVLAARI, and Vir for the development of ALN-COV and other potential RNAi therapeutics targeting SARS-CoV-2 and host factors for SARS-CoV-2; the outcome of litigation; the risk of government investigations and unexpected expenditures; as well as those risks more fully discussed in the 'Risk Factors' filed with Alnylam's most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) and in other filings that Alnylam makes with the SEC. In addition, any forward-looking statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements.

ALN-HSD has not been evaluated by the FDA, EMA, or any other regulatory authority and no conclusions can or should be drawn regarding the safety or effectiveness of this investigational therapeutic.

Contact:

Christine Regan Lindenboom

Tel: 617-682-4340

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Alnylam Pharmaceuticals : Submits CTA Application for ALN-HSD, an Investigational RNAi Therapeutic for the Treatment of Nonalcoholic Steatohepatitis -...

A research team at Samsung Medical Center has found that the younger the patients age, the higher the probability of finding the causative gene of infant epilepsy.

Epilepsy is a neurological disease caused by a variety of causes. However, it is difficult to find the cause of the outbreak, and hospitals conduct various tests and treatment methods to customize treatment for each patient. In some cases, patients develop epilepsy at a very young age, despite their brain MRI test results coming back normal. There remain high unmet needs for a diagnosis to establish the cause.

To resolve the issue, the team, led by Professors Lee Ji-won and Lee Ji-hoon, conducted a genetic panel test using next-generation sequencing on 116 patients under two years of age diagnosed with epilepsy despite having a normal brain MRI.

As a result of the study, the probability of finding the cause gene through genetic panel examination was 34.5 percent for patients under two years of age, 39.6 percent for those under one year old, and 50 percent for babies under six months old.

Until now, it was common for patients, who had epilepsy despite having a normal brain MRI, to receive antiepileptic drugs, the team said. Based on the results of this study, however, we think we have paved the way for selecting an appropriate drug according to the mutation of the causal gene.

In an additional study involving 13 benign rolandic epilepsy patients, the researchers could also diagnose the patients early and quickly provide optimal drugs, it added.

Although more than 50 percent of patients have yet to find the cause of their disease, the team expects to find more causal genes through the ongoing familial genome research, Professor Lee Ji-won said. To establish effective customized treatments, research is underway to produce a cell model that expresses the phenotype of a patient whose causative gene has been identified and screen the therapeutic agent.

Professor Lee Ji-hoon also said, Identifying the genes that cause epilepsy through the diagnostic capabilities of pediatrics clinicians can be a crucial aid in selecting therapeutic drugs, allowing doctors to predict to some extent what prognosis the young patients will show as they grow up.

Molecular Genetics & Genomic Medicine has published the results of the study.

corea022@docdocdoc.co.kr

< Korea Biomedical Review, All rights reserved.>

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'The younger the child, the likelier to find causative gene of infant epilepsy' - Korea Biomedical Review - Korea Biomedical Review

3 August 2020

Thirty-three genes associated with male infertility have been identified through a 'genomics-first' approach to understanding the condition.

Researchers from the King Faisal Specialist Hospital and Research Centre in Saudi Arabia used exomesequencing, a method for sequencingall the protein-coding regions of genesin a genome, to establish a genetic basis for infertility in male patients. It is hoped that a more complete understanding of the molecularbiology behind male infertility, alongside greater application of genomic medicine, will lead to improvements in treatment and diagnosis.

'Male factors account for nearly half of infertility caseswith nearly seven percent of the male population estimated to suffer from infertility' the authors reported in the journal Genetics in Medicine. 'However, current estimates of the contribution of genetics to male infertility (15 percent) suffer from the lack of comprehensive genomic analysis in large cohorts.'

From a non-selected sample of 285 infertile male patients, 69 (24.2 percent) were suspected of displaying a monogenic form of male infertility, meaning that it was caused by a defect in a single gene. Over 400 genes have already been associated with male infertility in mouse models, suggesting that that the monogenic contribution in humans has been significantly underestimated.

The current standard method for diagnosing the cause of male infertility involves screening for chromosomal aberrations, such as Y-chromosome micro-deletions too small to spot by karyotype. However, this technique has a low diagnostic yield, and aberrations were only identified in 30 (10.5 percent) of the patients included in the study.

Of the 285 patients included in the study, 237 presented with non-obstructive azoospermia a failure to make sperm resulting in no sperm in the ejaculate. The remaining 48 patients displayed severe oligospermia, characterised by a sperm count lower than one million sperm per millilitre. An identical number of fertile men were recruited to the study as controls.

'The 33 candidate genes we identified in this study represents by far the largest number of male infertility genes discovered by a single study,' Dr Fowzan Alkuraya, the principal clinical scientist behind the study toldGenomeWeb. 'There are only around 40 genes linked to non-obstructive azoospermia in humans. Thus, our study nearly doubles the genes linked to this phenotype.'

These candidate genes were also selected and verified based on known biological roles in male germ celldevelopment, as well as from compatible mouse models. Three of these genes were deemed as having 'strong evidence' of a connection to male infertility in humans, based on evidence from mouse models, as well as displaying independent variants in multiple unrelated patients.

The scientists are hopeful that these results will encourage further research dissecting the molecular basis of male infertility, as well as the development of future therapies and methods to improve its diagnosis and management.

Link:

Known genes associated with male infertility doubled - BioNews

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, announced today that the Company has submitted a clinical trial authorization (CTA) application to The Medicines and Healthcare Products Regulatory Agency (MHRA) in the United Kingdom to initiate a Phase 1 study of ALN-HSD, an investigational RNAi therapeutic targeting HSD17B13 for the treatment of nonalcoholic steatohepatitis (NASH). The Company plans to initiate a Phase 1 study in late 2020, upon obtaining MHRA approval.

We are excited to advance our ALN-HSD program to the clinic in partnership with Regeneron, particularly given the mass prevalence and high unmet need in NASH, a progressive disease associated with high morbidity and mortality. Given the genetic validation of the target, we believe ALN-HSD has the potential to change the course of this serious and potentially life-threatening disease for which there are currently no approved pharmacologic treatment options, said David Erbe, Ph.D., Senior Distinguished Investigator, Program Leader, ALN-HSD program at Alnylam. Pending feedback from the MHRA, we look forward to initiating the Phase 1 study to evaluate the safety and preliminary pharmacodynamic activity of ALN-HSD in healthy volunteers and patients with NASH.

About ALN-HSD

ALN-HSD is an investigational, subcutaneously administered RNAi therapeutic targeting HSD17B13 in development in collaboration with Regeneron Pharmaceuticals for the treatment of nonalcoholic steatohepatitis. ALN-HSD utilizes Alnylam's Enhanced Stabilization Chemistry Plus (ESC+) GalNAc-conjugate technology, which enables subcutaneous dosing with increased selectivity and a wide therapeutic index. The safety and efficacy of ALN-HSD have not been evaluated by the FDA, EMA or any other health authority.

About NASH

Nonalcoholic steatohepatitis (NASH) is a highly prevalent chronic liver disease in which inflammation and liver cell injury are caused by accumulation of hepatic fat. NASH is a subset of a group of conditions called nonalcoholic fatty liver disease (NAFLD) that can lead to progressive fibrosis, cirrhosis, and hepatocellular carcinoma. Comorbidities include obesity, metabolic syndrome, and type 2 diabetes. Approximately 16 million people in the US live with NASH, with prevalence of the disease increasing due to rising rates of obesity. NASH is projected to be the leading indication for liver transplants in developed countries within the next 10 years. There are currently no approved medical therapies for NASH.

About RNAi

RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines, known as RNAi therapeutics, is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, function upstream of todays medicines by potently silencing messenger RNA (mRNA) the genetic precursors that encode for disease-causing or disease pathway proteins, thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases.

About Alnylam Pharmaceuticals

Alnylam (Nasdaq: ALNY) is leading the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of people afflicted with rare genetic, cardio-metabolic, hepatic infectious, and central nervous system (CNS)/ocular diseases. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach for the treatment of a wide range of severe and debilitating diseases. Founded in 2002, Alnylam is delivering on a bold vision to turn scientific possibility into reality, with a robust RNAi therapeutics platform. Alnylams commercial RNAi therapeutic products are ONPATTRO (patisiran), approved in the U.S., EU, Canada, Japan, Brazil, and Switzerland, and GIVLAARI (givosiran), approved in the U.S., EU, and Brazil. Alnylam has a deep pipeline of investigational medicines, including six product candidates that are in late-stage development. Alnylam is executing on its "Alnylam 2020" strategy of building a multi-product, commercial-stage biopharmaceutical company with a sustainable pipeline of RNAi-based medicines to address the needs of patients who have limited or inadequate treatment options. Alnylam is headquartered in Cambridge, MA. For more information about our people, science and pipeline, please visit http://www.alnylam.com and engage with us on Twitter at @Alnylam or on LinkedIn.

Alnylam Forward-Looking Statements

Various statements in this release concerning Alnylam's future expectations, plans and prospects, including, without limitation, the potential of investigational RNAi therapeutics, in particular ALN-HSD, Alnylam's filing of a CTA for ALN-HSD and its expectations regarding the anticipated timing for initiation of a Phase 1 study of ALN-HSD, and expectations regarding the continued execution on its Alnylam 2020 guidance for the advancement and commercialization of RNAi therapeutics, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results and future plans may differ materially from those indicated by these forward-looking statements as a result of various important risks, uncertainties and other factors, including, without limitation: the direct or indirect impact of the COVID-19 global pandemic or a future pandemic, such as the scope and duration of the outbreak, government actions and restrictive measures implemented in response, material delays in diagnoses of rare diseases, initiation or continuation of treatment for diseases addressed by Alnylam products, or in patient enrollment in clinical trials, potential supply chain disruptions, and other potential impacts to Alnylams business, the effectiveness or timeliness of steps taken by Alnylam to mitigate the impact of the pandemic, and Alnylams ability to execute business continuity plans to address disruptions caused by the COVID-19 or a future pandemic; Alnylam's ability to discover and develop novel drug candidates and delivery approaches and successfully demonstrate the efficacy and safety of its product candidates; the pre-clinical and clinical results for its product candidates, which may not be replicated or continue to occur in other subjects or in additional studies or otherwise support further development of product candidates for a specified indication or at all; actions or advice of regulatory agencies, which may affect the design, initiation, timing, continuation and/or progress of clinical trials or result in the need for additional pre-clinical and/or clinical testing; delays, interruptions or failures in the manufacture and supply of its product candidates, including ALN-HSD, or its marketed products; obtaining, maintaining and protecting intellectual property; intellectual property matters including potential patent litigation relating to its platform, products or product candidates; obtaining regulatory approval for its product candidates, including ALN-HSD, and maintaining regulatory approval and obtaining pricing and reimbursement for its products, including ONPATTRO and GIVLAARI; progress in continuing to establish a commercial and ex-United States infrastructure; successfully launching, marketing and selling its approved products globally, including ONPATTRO and GIVLAARI, and achieving net product revenues for ONPATTRO within its revised expected range during 2020; Alnylams ability to successfully expand the indication for ONPATTRO in the future; competition from others using technology similar to Alnylam's and others developing products for similar uses; Alnylam's ability to manage its growth and operating expenses within the ranges of guidance provided by Alnylam through the implementation of further discipline in operations to moderate spend and its ability to achieve a self-sustainable financial profile in the future without the need for future equity financing; Alnylams ability to establish and maintain strategic business alliances and new business initiatives, including completing an agreement for funding by Blackstone of certain R&D activities for vutrisiran and ALN-AGT; Alnylam's dependence on third parties, including Regeneron, for development, manufacture and distribution of certain products, including eye and CNS products, Ironwood, for assistance with the education about and promotion of GIVLAARI, and Vir for the development of ALN-COV and other potential RNAi therapeutics targeting SARS-CoV-2 and host factors for SARS-CoV-2; the outcome of litigation; the risk of government investigations; and unexpected expenditures; as well as those risks more fully discussed in the "Risk Factors" filed with Alnylam's most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) and in other filings that Alnylam makes with the SEC. In addition, any forward-looking statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements.

ALN-HSD has not been evaluated by the FDA, EMA, or any other regulatory authority and no conclusions can or should be drawn regarding the safety or effectiveness of this investigational therapeutic.

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Alnylam Submits CTA Application for ALN-HSD, an Investigational RNAi Therapeutic for the Treatment of Nonalcoholic Steatohepatitis (NASH) - Business...

Huma Q. Rana, MD, MPH, discusses the rationale for the ProGen trial, which compared the effectiveness of video education versus in-person genetic counseling for men with prostate cancer.

Huma Q. Rana, MD, MPH, anassistant professor of medicine at Harvard Medical School andclinical directorofCancer Genetics and Prevention at Dana-Farber Cancer Institute, discusses the rationale for the ProGen trial, which compared the effectiveness of video education versus in-person genetic counseling for men with prostate cancer.

There are increasing indications for germline genetic testing in prostate cancer, says Rana. Through several clinical studies, the field has recognized that there is a high prevalence of inherited mutations among men with advanced prostate cancers, and this could have significant implications on treatment. Men with advanced prostate cancer, particularly those with underlying mutations in genes such asBRCA2, are known to have poor outcomes, says Rana. Therefore, it is important to identify these men and make matched targeted therapy available to them and their oncologists.

In recognizing that prostate cancer is a very common disease and that traditional germline genetic testing would be very difficult to implementpotentially overwhelming already strained systems for genetic testinga randomized controlled trialwas conducted. In the trial, investigators compared the effectiveness of a short videothat focused on the educational components of a genetic counseling visit with in-person genetic counseling for men with potentially lethal prostate cancers, concludes Rana.

Link:

Dr. Rana on the Rationale for Video Genetic Counseling in Prostate Cancer - OncLive