GAITHERSBURG, Md., April 14, 2020 (GLOBE NEWSWIRE) -- OpGen, Inc. (Nasdaq: OPGN, OpGen), a precision medicine company harnessing the power of molecular diagnostics and informatics to help combat infectious disease, announced today that total revenue for the first quarter of 2020 was approximately $617,000 down from $1.0 million in the first quarter of 2019, excluding revenues from the Curetis businesses, which was acquired upon closing of the business combination on April 1, 2020. Cash as of March 31, 2020 was approximately $11.5 million, up significantly from the $2.7 million as of December 31, 2019.

The company also announced accomplishment of the following key milestones, including key business milestones achieved by Curetis and Ares Genetics in the first quarter of 2020:

OpGen revenue during the first quarter of 2020 can be attributed to Acuitas AMR Gene Panel and Acuitas Lighthouse revenue, which was approximately $254,000, while revenues from the companys rapid FISH products decreased to $363,000. The company expects to provide full first quarter 2020 financial results during its first quarter 2020 earnings call in early May of this year.

Oliver Schacht, President and CEO of OpGen commented, In light of the unprecedented crisis situation with COVID-19, we were pleased with the robust first quarter 2020 initial results. We have been humbled and extremely encouraged by the dedication and hard work put in place by all our employees globally during these extraordinary times. Going forward and once this crisis is behind us, we anticipate dynamic growth in our business trajectory following the expected near-term FDA clearance decision of our Acuitas AMR Gene Panel. We also expect the CoV-2 test kit sales in Europe to continue contributing to our top-line revenue in Q2 of 2020.

Schacht continued, Now operating as one combined company, OpGen with its group companies Curetis and Ares Genetics boast strong proprietary assets for developing and commercializing innovative, data-driven solutions in infectious disease diagnostics, and we look forward to the continued integration of our businesses over the coming weeks and months.

The preliminary financial results are estimates prior to the completion of OpGensfinancial closing procedures and review procedures by its external auditors and therefore may be subject to adjustment when the actual results are available.

About OpGen, Inc.

OpGen, Inc. (Gaithersburg, MD, USA) is a precision medicine company harnessing the power of molecular diagnostics and bioinformatics to help combat infectious disease. Along with subsidiaries, Curetis GmbH and Ares Genetics GmbH, we are developing and commercializing molecular microbiology solutions helping to guide clinicians with more rapid and actionable information about life threatening infections to improve patient outcomes, and decrease the spread of infections caused by multidrug-resistant microorganisms, or MDROs. OpGens product portfolio includes Unyvero, Acuitas AMR Gene Panel and Acuitas Lighthouse, and the ARES Technology Platform including ARESdb, using NGS technology and AI-powered bioinformatics solutions for antibiotic response prediction.

For more information, please visit http://www.opgen.com.

Forward-Looking Statements

This press release includes statements regarding the pursuit of FDA clearance for the Acuitas AMR Gene Panel for use with bacterial isolates, the integration of OpGen with its acquired subsidiaries, Curetis GmbH and Ares Genetics GmbH, and activities related to the companys products and services. These statements and other statements regarding OpGens future plans and goals constitute "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934 and are intended to qualify for the safe harbor from liability established by the Private Securities Litigation Reform Act of 1995. Such statements are subject to risks and uncertainties that are often difficult to predict, are beyond our control, and which may cause results to differ materially from expectations. Factors that could cause our results to differ materially from those described include, but are not limited to, our ability to successfully, timely and cost-effectively develop, seek and obtain regulatory clearance for and commercialize our product and services offerings, the rate of adoption of our products and services by hospitals and other healthcare providers, the realization of expected benefits of our business combination transaction with Curetis GmbH, the success of our commercialization efforts, the effect on our business of existing and new regulatory requirements, and other economic and competitive factors. For a discussion of the most significant risks and uncertainties associated with OpGen's business, please review our filings with the Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which are based on our expectations as of the date of this press release and speak only as of the date of this press release. We undertake no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise.

OpGen:Oliver SchachtPresident and CEOInvestorRelations@opgen.com

OpGen Press Contact:Matthew BretziusFischTank Marketing and PR matt@fischtankpr.com

OpGen Investor Contact:Joe Green Edison Groupjgreen@edisongroup.com

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OpGen Announces Preliminary Unaudited Revenue and Cash Position for First Quarter 2020 and Provides Business Update - GlobeNewswire

Majority of potential study participants have been pre-screened

EB-101 successfully manufactured at Abeona and transplanted at Stanford University Medical Center

NEW YORK and CLEVELAND, March 17, 2020 (GLOBE NEWSWIRE) -- Abeona Therapeutics Inc. (Nasdaq: ABEO), a fully-integrated leader in gene and cell therapy, today announced that investigators at Stanford University Medical Center have treated the first patient in the pivotal phase III VIITAL study evaluating EB-101, the Companys gene-corrected cell therapy for recessive dystrophic epidermolysis bullosa (RDEB).

Treating the first patient in our pivotal Phase III VIITAL study is an important achievement for the EB-101 program, now the most advanced gene therapy program in RDEB, said Joo Siffert, M.D., Chief Executive Officer. This achievement confirms that Abeona can deliver EB-101 in a study setting that closely parallels its potential real-world application. We remain confident that VIITALTM will replicate results from the Phase I/II trial demonstrating that EB-101 treatment resulted in sustained and durable wound healing with a favorable safety profile.

The VIITALPhase III study is a multi-center, randomized clinical trial assessing EB-101 in up to 15 RDEB patients, with approximately 30 large, chronic wound sites treated in total. The primary outcome measure is wound healing, comparing treated with untreated wound sites on the same patient.Secondary endpoints include the assessments of pain, as well as other patient reported outcomes. Investigators at Stanford University Medical Center are currently enrolling eligible patients into the VIITALTM study and preparations for an additional clinical site initiation are ongoing. Additional information about the trial is available at abeonatherapeutics.com/clinical-trials/rdeb.

Abeona is producing EB-101 for the VIITALTM study at the Elisa Linton Center for Rare Disease Therapies, its fully-functional gene and cell therapy manufacturing facility centrally-located in Cleveland, OH. The 26,000 ft2 center is housing large-scale cGMP capacity for AAV gene therapy and EB-101 cell therapy manufacturing, and state-of-the-art laboratories to support CMC development for process and analytics, all of which is validated and governed by comprehensive quality systems and overseen by experienced staff.

About EB-101EB-101 is an autologous, gene-corrected cell therapy in late-stage clinical development for the treatment of recessive dystrophic epidermolysis bullosa (RDEB), a rare connective tissue disorder without an approved therapy. Treatment with EB-101 involves using gene transfer to deliver COL7A1 genes into a patients own skin cells (keratinocytes and its progenitors) and transplanting them back to the patient to enable normal Type VII collagen expression and facilitate wound healing. Data from a Phase I/IIa clinical trial conducted by Stanford University evaluating EB-101 showed that the gene-corrected cell therapy provided durable wound healing for RDEB patients lasting 2+ to 5+ years, including for the largest, most challenging wounds that affect the majority of the RDEB population. In the U.S., Abeona holds Regenerative Medicine Advanced Therapy, Breakthrough Therapy, and Rare Pediatric designations for EB-101 and Orphan Drug designation in both the U.S. and EU.

About Recessive Dystrophic Epidermolysis BullosaRecessive dystrophic epidermolysis bullosa (RDEB) is a rare connective tissue disorder characterized by severe skin wounds that cause pain and can lead to systemic complications impacting the length and quality of life. People with RDEB have a defect in the COL7A1 gene, leaving them unable to produce functioning Type VII collagen which is necessary to anchor the dermal and epidermal layers of the skin. There is currently no approved treatment for RDEB.

About Abeona Therapeutics Abeona Therapeutics Inc. is a clinical-stage biopharmaceutical company developing gene and cell therapies for serious diseases. The Companys clinical programs include EB-101, its autologous, gene-corrected cell therapy for recessive dystrophic epidermolysis bullosa, as well as ABO-102 and ABO-101, novel AAV9-based gene therapies for Sanfilippo syndrome types A and B (MPS IIIA and MPS IIIB), respectively. The Companys portfolio of AAV9-based gene therapies also features ABO-202 and ABO-201 for CLN1 disease and CLN3 disease, respectively. Abeona has received numerous regulatory designations from the FDA and EMA for its pipeline candidates, including Regenerative Medicine Advanced Therapy designation for two candidates (EB-101 and ABO-102). http://www.abeonatherapeutics.com

Forward Looking StatementThis press release contains certain statements that are forward-looking within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and that involve risks and uncertainties. These statements include statements about the Companys clinical trials, including the timing and success thereof; the Companys products and product candidates; EB-101 can provide durable healing in large, chronic wounds that afflict many RDEB patients; future regulatory interactions with regulatory authorities; and the Companys goals and objectives. We have attempted to identify forward-looking statements by such terminology as may, will, believe, estimate, expect, and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances), which constitute and are intended to identify forward-looking statements. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, numerous risks and uncertainties, including but not limited to continued interest in our rare disease portfolio, our ability to enroll patients in clinical trials, the outcome of any future meetings with the U.S. Food and Drug Administration or other regulatory agencies, the impact of competition, the ability to secure licenses for any technology that may be necessary to commercialize our products, the ability to achieve or obtain necessary regulatory approvals, the impact of changes in the financial markets and global economic conditions, risks associated with data analysis and reporting, and other risks as may be detailed from time to time in the Companys Annual Reports on Form 10-K and quarterly reports on Form 10-Q and other periodic reports filed by the Company with the Securities and Exchange Commission. The Company undertakes no obligation to revise these forward-looking statements or update them to reflect events or circumstances occurring after the date of this presentation, whether as a result of new information, future developments or otherwise, except as required by the federal securities laws.

Investor Contact:Dan FerryLifeSci Advisors, LLC+1 (617) 535-7746daniel@lifesciadvisors.com

Media Contact:Scott SantiamoDirector, Corporate CommunicationsAbeona Therapeutics+1 (718) 344-5843ssantiamo@abeonatherapeutics.com

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Abeona Therapeutics Announces First Patient Treated in Pivotal Phase III Clinical Trial Evaluating EB-101 Gene Therapy for Recessive Dystrophic...

A study published in Precision Oncology demonstrates that RNA genetic testing, conducted at the same time as DNA testing, identifies more genetic mutations that increase genetic cancer risk than DNA testing alone.[1]

The results of the study shows the first notable improvement in diagnostic yield for high-risk cancer genes in more than 10 years.

Using +RNAinsight, Ambry Genetics, a division of Konica Minolta Precision Medicine, is the first laboratory offering concurrent RNA and DNA genetic testing for hereditary cancer risk as a commercially available clinical test.

+RNAinsight, paired with Ambry Genetics hereditary cancer DNA tests, uses next-generation sequencing to concurrently analyze a patients DNA and RNA. This approach not only improves the sensitivity and clarity of genetic testing, it works in tandem with DNA testing to identify patients with or at-risk for hereditary cancer who might otherwise be missed, decrease variants of unknown significance (VUS) in real-time, and provide more accurate results to inform patient care.[2]

Mutations, Variants or errorsOverall, more than 50 hereditary cancer syndromes have been described. Most of these cancers are caused by harmful mutations, also known as variants or errors, that are inherited in an autosomal dominant fashion in which a single altered copy of a gene inherited from one parent is enough to increase a persons chance of developing cancer. In addition, a number of tests screen for inherited genetic variants that are not associated with named syndromes but have been found to increase cancer risk. This, for example, includes inherited variants in PALB2, which is associated with increased risks of breast and pancreatic cancers, CHEK2, associated with breast and colorectal cancers, BRIP1, RAD51C and RAD51D, associated with ovarian cancer.[3]

Overall, these mutations in our DNA increase cancer risk, play a major role in about 5% 10% of all cancers. Genetic testing identifies these inherited mutations and is a critical tool to prevent hereditary cancers or treat them early.

However, standard DNA testing for hereditary cancer risk excludes portions of DNA, and, as a result, misses some mutations. In addition, DNA testing can produce inconclusive results and fail to determine whether a variant increases cancer risk.

These limitations impact patients and their families because doctors may not have the information needed to recommend appropriate preventive, early-detection, or therapeutic steps. Furthermore, relatives may not be referred for genetic testing and obtain the care they would otherwise have gotten if they had learned they had certain mutations.

RNA genetic testingAdding RNA genetic testing at the same time as DNA testing helps address these limitations. Specifically, RNA genetic testing is an additional line of evidence that helps determine that an uncertain result from DNA-only testing is either benign or pathogenic.

In addition, RNA generic testing also helps identify mutations that DNA-only testing misses.

In the study published Precision Oncology, the authors describe their scalable and targeted approach to RNA genetic testing that is performed concurrently with DNA genetic testing, demonstrating such an approach that identified more mutations than DNA-only testing.

Working together with 19 other leading clinical institutions across the United States, including Mass General Cancer Center, Huntsman Cancer Institute, and the Perelman School of Medicine at the University of Pennsylvania, researchers at Ambry Genetics looked at 18 tumor suppressor genes where the loss of function is known to be associated with increased cancer. Their work resulted in a prospective study on the first 1,000 patients sent in for hereditary cancer testing using RNA testing coupled with DNA.

The study found that RNA testing identified seven patients with pathogenic mutations that would otherwise have received negative or inconclusive results on DNA testing alone. For six of these seven cases, substantial changes to medical management could be or were recommended based on current guidelines.

FeasibilityThe study findings demonstrate both the feasibility and clinical utility of adding concurrent RNA genetic testing to determine hereditary cancer risk, said Tyler Landrith, Ph.D., an Ambry scientist, and study co-author.

[Our] +RNAinsight provides healthcare providers with more accurate results to inform patient care, Landrith added.

Relative increaseThe prospective analysis showed a 9.1% relative increase in diagnostic yield than DNA testing alone. Adding RNA genetic testing also resulted in a 5.1% relative decrease in the number of patients that otherwise would have received inconclusive results with DNA testing alone and would not have learned whether they had increased cancer risk.

Paired RNA and DNA genetic testing have given answers to my patients who have struggled for years with inconclusive results that left them feeling helpless, said Community Health Network Genetic Counselor Rebekah Krukenberg.

With +RNAinsight, I know that Im providing my patients with the most accurate and conclusive information about their risks for hereditary cancer, she explained.

AccuracyThe study also validated the accuracy of +RNAinsight, establishing a large control dataset of healthy patients. This dataset allowed study authors to establish a baseline for benign and disease-causing variants across the genes tested.

Previous studies have demonstrated the benefits of RNA genetic testing. However, testing has been traditionally performed as a follow-up to inconclusive DNA testing. This approach to RNA testing has limitations that Ambry Genetics +RNAinsight does not have.

Testing at the same timeA previous study showed that only 10% percent of patients invited to receive RNA testing after having undergone DNA testing actually sent in samples. Moreover, retrospective RNA testing only looks at targeted variants and not a full range of possible mutations. Given these limitations, +RNAinsight is made available to all patients at the same time as DNA testing.[4]

Reference[1] Landrith, T., Li, B., Cass, A.A. et al. Splicing profile by capture RNA-seq identifies pathogenic germline variants in tumor suppressor genes. npj Precis. Onc. 4, 4 (2020). https://www.nature.com/articles/s41698-020-0109-y%5B2%5D Karam R., Krempelyl K, Richardson ME, McGoIdrickl K, Zimmermann H, Connerl B, Landrithl T, et al., RNA Genetic Testing in Hereditary Cancer Improves Variant Classification and Patient Management. Annual Clinical Genetics Meeting (ACMG) 2019 [Poster][3] Cancer Causes and prevention. Genetic Testing for Inherited Cancer Susceptibility Syndromes. What genetic tests are available for cancer risk assessment? National Cancer Institute. Online Last accesses February 24, 2020.[4] Karam R, Conner B, LaDuca H, McGoldrick K, Krempely K, Richardson ME, Zimmermann H, et al. Assessment of Diagnostic Outcomes of RNA Genetic Testing for Hereditary Cancer. JAMA Netw Open. 2019;2(10):e1913900. doi:10.1001/jamanetworkopen.2019.13900 [Article]

Excerpt from:
+RNAinsight Identifies More Patients with Increased Hereditary Cancer Risk vs. DNA-only Test - OncoZine

ClinGen is funded by the National Human Genome Research Institute (NHGRI), which is itself part of the National Institutes of Health. Erin Ramos, PhD, a project scientist for ClinGen and program director for the division of genomic medicine at NHGRI, said in a release that NHGRI developed ClinGen as a way to standardize guidelines for genetic testing. A panel of experts, including researchers, clinicians and genetic counselors comb through scientific evidence from research papers to identify gene-disease relationships as either definitive, strong, moderate, limited, disputed or refuted.

The experts reported that three genesKCNQ1, KCNH2 and SCN5Awere indeed backed by enough evidence to be categorized as definitive genetic triggers for long QT syndrome. They classified four other genes as either strong or definitive for causing atypical forms of long QT syndrome, but the panel didnt find enough evidence to support the remaining 10 genes.

Those 10 genes were all placed in either the limited or disputed category for their link to long QT syndrome, and for that reason the authors said they dont recommend using them as markers in routine clinical tests.

Our study highlights the need to take a step back and to critically evaluate the level of evidence for all reported gene-disease associations, especially when applying genetic testing for diagnostic purposes in our patients, Gollob said in a statement. Testing genes with insufficient evidence to support disease causation only creates a risk of inappropriately interpreting the genetic information and leading to patient harm.

Read the rest here:
Experts dispute 9 of 17 genes once linked to long QT syndrome - Cardiovascular Business

The World Health Organization (WHO) recently declared an international public health emergency over the global outbreak of the novel coronavirus. One day later, the Wellcome Trust research charity called for researchers, journals and funders around the world to share research data and findings relevant to the coronavirus rapidly and openly, to inform the public and help save lives.

On the same day, the China National Knowledge Infrastructure launched a free website and called for scientists to publish research on the coronavirus with open access. Shortly after, the prominent scientific journal Nature issued an editorial urging all coronavirus researchers to keep sharing, stay open.

So while cities are locked down and borders are closed in response to the coronavirus outbreak, science is becoming more open. This openness is already making a difference to scientists response to the virus and has the potential to change the world.

But its not as simple as making every research finding available to anyone for any purpose. Without care and responsibility, there is a danger that open science can be misused or contribute to the spread of misinformation.

Open science can come in a variety of forms, including open data, open publications and open educational resources.

1. Open data

DNA sequencing is of great importance to developing specific diagnostic kits around the world. Yong-Zhen Zhang and his colleagues from Fudan University in Shanghai were the first to sequence the DNA of the novel coronavirus. They placed the gene sequence in GenBank, an open-access data repository. Researchers around the world immediately started analysing it to develop diagnostics.

As of February 19 2020, 81 different coronavirus gene sequences had been shared openly via GenBank and 189 via the China National Genomics Data Centre. They provide the data that will allow scientists to decode the mystery of the virus and hopefully find a treatment or vaccine.

The WHO and national organisations like the Chinese Center for Disease Control and Prevention also publish open statistical data, such as the number of patients. This can help researchers to map the spread of the virus and offer the public up-to-date and transparent information.

2. Open publications

Science publications are costly. One of the most expensive Elsevier journals, Tetrahedron Letters, costs 16,382 for an institutional annual subscription and 673 for a personal one. Even the University of Harvard cannot afford to subscribe to all journals. This means not all researchers have access to all subscription-based publications.

Authors can publish their articles free to access, which often means they need to pay the publishers an average 2,000 in article processing costs. In 2018, only 36.2% of science publications were open-access.

As of February 18 2020, there were 500 scientific articles about the novel coronavirus in the comprehensive scholarly database Dimensions. Only 160 (32%) of them were in open-access publications. This includes preprint servers such as bioRxiv and arXiv, which are widely used open-access archives to publish research before it goes through scientific peer review.

Normally, you would need to pay subscription fees to read any of the other 340 articles. However, articles published by the 100 companies who have signed the Wellcome Trusts statement on sharing coronavirus research have been made freely accessible by publishers.

Major publishers including Elsevier, Springer Nature, Wiley Online Library, Emerald, Oxford University Press and Wanfang have also set up featured open-access resources page. The Chinese database CQVIP has offered free access to all of its 14,000 journals during the coronavirus outbreak.

As it takes on average 160 days for a preprint to be published after peer review, sharing preprints can save time and save life. Free access to articles on the coronavirus can also accelerate global research on this subject.

3. Open educational resources

Due to the outbreak, universities in China have postponed their new semesters and switched to online learning. But alongside the 24,000 online courses open to students, universities (including the elite Peking University, Tsinghua University and Xian Jiaotong University) are offering free online courses to the public about the coronavirus. Such courses can offer the public reliable information grounded in academic research, helping them better understand and protect themselves against the virus.

While all these developments are positive, it is important to remember that open science doesnt mean science without limits. It must be used responsibly by researchers and the public.

To start, researchers need to have mutual respect for the integrity of their work. For example, there have reportedly already been disagreements over whether scientists need to request consent to reuse pre-publication data from shared coronavirus gene sequencing.

Assuming researchers act in good faith and not to simply further their own careers, it is still important for them to clarify the conditions with which they make their research available, and to carefully check and follow such conditions when using other peoples data. Responsible uses of pre-publication data are vital to fostering a scientific culture that encourages transparent and explicit cooperation.

There are also issues with making research available without peer review - as happens with preprint servers - as misinterpretations and mistakes can easily happen. One paper posted on bioRxiv on February 2 2020 claimed to show insertions in the coronaviruss DNA that showed an uncanny similarity to regions found in HIV DNA.

After criticism of the their work, the papers authors withdrew it stating they did not intend to feed into the conspiracy theories that the novel coronavirus had been deliberately engineered. Such conspiracy theories were recently condemned by 27 scientists from eight countries in their open statement to the leading medical journal The Lancet.

Yet until February 19 2020, the withdrawn paper was the most discussed study in the world in online news and social media, according to the academic ranking site Altmetric. The paper may have been withdrawn but it wont have been forgotten.

Open science is vital to tackling the worlds big challenges. But when information can be misused, skewed or misinterpreted at global level so quickly, we also need scientists and the public to treat open science with great care and responsibility.

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The hunt for a coronavirus cure is showing how science can change for the better - The Conversation UK

Precision medicine promises a new paradigm in oncology where every patient receives truly personalized treatment. This approach to disease diagnosis, treatment and prevention utilizes a holistic view of the patientfrom their genes and their environment to their lifestyleto make more accurate decisions.

Growing at a rate of 10.7 percent, the precision medicine market is expected to exceed $96 billion by 2024.1 Bioinformatics represent a significant share of the market, as bioinformatics tools enable the data mining necessary for rapid identification of new drug targets and repurposing of existing treatments for new indications.1 (Reuters) The oncology segment of the precision market is expected to experience an 11.1 percent compounded annual growth rate (CAGR) leading up to 2024 due to the success of recent targeted therapies and subsequent high demand.

Still, precision medicine is in its infancy, and making personalized treatment a reality for all patients requires a transformation in how novel therapies are developed and delivered. New regulatory, technical, clinical and economic frameworks are needed to ensure that the right patients are able to access the right therapy at the right time. In this article, we review the current state of precision medicine in oncology and explore some of the challenges that must be addressed for precision medicine to reach its full potential.

Great strides toward precision medicine are being made in the area of cancer immunotherapy, which is designed to boost a patients own immunity to combat tumor cells. The introduction of immune checkpoint inhibitors (PD-1/PD-L1 and CTLA-4 inhibitors) revolutionized treatment for certain hematologic malignancies and solid tumors. To date, immune checkpoint inhibitors have been approved by the U.S. Food and Drug Administration (FDA) for more than 15 cancer indications, but their widespread use has been hampered by unpredictable response rates and immune-related adverse events.

The approvals of the first chimeric antigen receptor (CAR)-T cell (CAR-T) therapies in 2017 were the next leap forward in precision medicine. These immunotherapies demonstrated that it was possible to take out a patients own T-cells, genetically modify them, and then put them back in to target cancer cells. With complete remission rates as high as 83 percent within three months of treatment, CAR-T therapies represent a seismic shift in our approach to cancer, bringing the elusive possibility of a cure one step closer. However, longer-term follow-up has shown that these remissions may not be durable2 and prevention of relapse must still be studied.

Ultimately, the goal of cancer immunotherapy is to stimulate the suppressed immune system of a patient with cancer so that it can launch a sustained attack against tumor cells.3 This is complicated, as the interactions between tumors and immune systemsometimes called the Cancer-Immunity Cycle (see Figure 1 in the slider above)4are complex and dynamic. The Cancer-Immunity Cycle manages the delicate balance between the immune systems ability to recognize non-self and the development of autoimmunity.

In some cases, the immune system may fail to recognize tumor cells as non-self and may develop a tolerance to them. Moreover, tumors have an armamentarium of methods for evading the immune system. Given this elaborate interplay between cancer and immunity, there is a wide range of potential cancer immunotherapy approaches:

The immune response to cancer involves a series of carefully regulated events that are optimally addressed as a group, rather than individually.4 The complexity of the immune response to cancer provides a strong rationale for combination therapies, for instance:

Increasingly, the development and deployment of immunotherapy relies on harnessing genomic data to identify the patients most likely to respond to immunotherapy and to customize immunotherapy for a given patient.6 Thus, molecular profiling technologies, such as next-generation sequencing, have become integral to drug development and patient selection. At the same time, researchers are focusing on identifying molecular alterations in tumors that may be linked to response.7 The molecular fingerprints of a tumor can be quite complex and heterogeneous, not only across tumors, but also within a single patient. Consequently, molecular tumor characterization requires both multidimensional data from laboratory and imaging tests and advanced software and computational methods for analyzing these data.8 This emergence of computational precision oncology is associated with both opportunities and challenges, from validation and translation to regulatory oversight and reimbursement.

The regulatory landscape is evolving to keep pace with technological advances in cell engineering and gene editing. Since 2013, the FDA has published four guidance documents on cellular and gene therapy products, as well as two guidance documents providing recommendations on regenerative medicine advanced therapies (RMATs). Specifically, their Expedited Programs for Regenerative Medicine Therapies for Serious Conditions, published in November 2017, provides guidance on the expedited development and review of regenerative medicine therapies for serious or life-threatening diseases and conditions. This document also provides information on the use of the accelerated approval pathway for therapies that have been granted the RMAT designation.9

In the EU, the European Medicines Agency (EMA) published a draft revision of its Guideline on quality, non-clinical and clinical aspects of medicinal products containing genetically modified cells in July 2018.10 This draft revision includes current thinking on the requirements for nonclinical and clinical studies, as well as specific sections on the scientific principles and clinical aspects of CAR-T products.

Precision medicines such as CAR-T therapies require manufacturers to transform a complex, individualized treatment into a commercial product. In conventional manufacturing, the entire manufacturing process occurs within the confines of the manufacturing facility. With cell therapies, however, the process begins with the collection of cells from the patient and ends with administration of the final product (see Figure 2 in the slider above). In between, the cells are handed off multiple times for the process of genetic modification, creating a complex supply chain that blends manufacturing and administration.11

Moreover, in contrast to traditional manufacturing where the starting materials are standardized or well-defined, the starting materials for cell therapies are derived from patients and, thus, highly variable.

As evidenced by the manufacturing challenges that plagued the launch of Kymriah (tisagenlecleucel), even pharmaceutical giants have struggled with meeting label specifications for commercial use.13 To help address its manufacturing hurdles, Novartis acquired CellforCure, a contract development manufacturing organization, and plans to transform by focusing on data and digital technologies.14,15 What this means for sponsors is that robust, scalable manufacturing must be incorporated into clinical developing planning at its earliest stages.

The high price tags associated with CAR-T therapies illustrate how expensive targeted therapies are in comparison to their traditional counterparts.16 Existing health insurance models have not been structured to reimburse for costly treatments that offer the potential for long-term benefit or even cure. The pricing model for CAR-T therapies may be especially challenging for private insurance companies, which have higher turnover and shorter coverage windows than national health insurance programs. For sponsors of precision medicine therapies, one way to address the challenge of reimbursement is to create innovative, value- or outcomes-based pricing models, rather than focusing on sales volume. The success of these new pricing models will rely on patient selection. To demonstrate value and optimizing outcomes, sponsors will need to develop profiles of patients who are most likely to respond and provide tools for identifying these patients.8

Of note, on August 7, 2019, the Centers for Medicare & Medicaid Services (CMS) finalized the decision to cover FDA-approved CAR-T therapies when provided in healthcare facilities enrolled in the FDA risk evaluation and mitigation strategies (REMS) for FDA-approved indications. Medicare will also cover FDA-approved CAR-T treatments for off-label uses that are recommended by CMS-approved compendia.17

Beyond the pharmaceutical companies that are working to develop personalized treatments, the precision medicine ecosystem has a number of other key stakeholdersregulators, payers, diagnostic companies, healthcare technology companies, healthcare providers and, of course, patients. Pharmaceutical companies need to engage with each of these stakeholders by providing education or developing partnerships that help demonstrate the need for high-quality data collection, the value of precision medicine, and the process for identifying the right patients.

Sponsors may also benefit from engaging with patient advocacy groups as these groups play a critical role in connecting patients and caregivers with scientific and healthcare experts to learn about how new immunotherapy breakthroughs are changing the standard of care.

Empowered patients pushing for the latest innovations are propelling precision medicine forward, but we still have a way to go before the full potential of precision medicine is realized. In its maturity, precision medicine will not only enable the personalization of treatments for individual patients, but also inform public health at a population level as insights from the genetic and molecular data collected are used to advance our understanding of disease. Robust data collection and analysis, along with standardization, are required for building this foundation of precision medicine, and multi-stakeholder buy-in is necessary for addressing issues around data integration and privacy.

While significant challenges remain, the opportunity to transform patient outcomes and population health with precision medicine is tantalizing. Increasingly, we are seeing advanced technologiessuch as artificial intelligence and machine learningbeing incorporated into the drug discovery and development process. This underscores the critical need for a multidisciplinary approach to precision medicine, from discovery at the bench all the way through to delivery at the bedside, to help ensure that more patients can access the right therapy at the right time, and the right price.

References

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Realizing The Full Potential Of Precision Medicine In Oncology - Contract Pharma

More than 1,100 mutations in the TSC2 gene have been identified in individuals with tuberous sclerosis complex, a condition characterized by developmental problems and the growth of noncancerous tumors in many parts of the body. Most of these mutations insert or delete a small number of DNA building blocks (base pairs) in the TSC2 gene. Other mutations change a single base pair in the TSC2 gene or create a premature stop signal in the instructions for making tuberin.

People with TSC2-related tuberous sclerosis complex are born with one mutated copy of the TSC2 gene in each cell. This mutation prevents the cell from making functional tuberin from that copy of the gene. However, enough tuberin is usually produced from the other, normal copy of the TSC2 gene to regulate cell growth effectively. For some types of tumors to develop, a second mutation involving the other copy of the gene must occur in certain cells during a person's lifetime.

When both copies of the TSC2 gene are mutated in a particular cell, that cell cannot produce any functional tuberin. The loss of this protein allows the cell to grow and divide in an uncontrolled way to form a tumor. A shortage of tuberin also interferes with the normal development of certain cells. In people with TSC2-related tuberous sclerosis complex, a second TSC2 gene mutation typically occurs in multiple cells over an affected person's lifetime. The loss of tuberin in different types of cells disrupts normal development and leads to the growth of tumors in many different organs and tissues.

Link:
TSC2 gene - Genetics Home Reference - NIH

Decibel Therapeutics Industry veteran Laurence Reid has been tapped to serve as Boston-based Decibels acting chief executive officer. Current CEO Steven Holtzman is retiring and will become a strategic business advisor to the company. Reid is an entrepreneur-in-residence at Third Rock Ventures and has held numerous leadership positions in the biotech industry. Most recently, he served as the CEO of Warp Drive Bio, a drug discovery company advancing novel oncology and anti-infective medicines, and where he ultimately negotiated the successful merger of the company with Revolution Medicines in 2018. In his previous role as chief business officer of Alnylam Pharmaceuticals, he led business development, finance and legal functions.

Passage Bio Bruce Goldsmith was named CEO of Passage Bio. He succeeds Stephen Squinto, who co-founded Passage Bio and served as interim chief executive officer since 2018. Goldsmith joins Passage Bio from Deerfield Management where he was a venture partner responsible for early-stage investments and served as interim chief executive officer of Civetta Therapeutics. Previously, Goldsmith was chief operating officer at Lycera, a company developing first-in-class small molecules for immuno-oncology and autoimmune disease. Goldsmith also held senior positions at Allos Therapeutics and GPC Biotech as well as various strategic marketing and business development roles at Johnson & Johnson focused on oncology and virology.

Century Therapeutics -- Former Novartis CEO Joseph Jimenez joined the board of directors of Century Therapeutics. Jimenez joins Centurys board with more than 20 years of experience as a senior leadership executive in the pharmaceutical and consumer products industries. He retired in 2018 as the CEO of Novartis. Also, the company tapped Celgene veteran Greg Russotti as its chief technology officer. Russotti brings more than 25 years of industrial experience in bioprocess development and implementation, including extensive knowledge in cell therapy technical operations. Most recently, he was vice president of cell therapy technical development at Celgene, where he guided CMC efforts for five different cell therapy products to IND and clinical-stage development. Before Celgene, Russotti spent 12 years at Merck Research Laboratories with roles in cell culture development, downstream purification, pilot plant operations, and manufacturing facility startup.

H.E.L. Group -- H.E.L Group announced the appointment of three new members to its senior team, who will focus primarily on strengthening production and service support for its scientific instrumentation and software. The company appointed Roy Eggleston to the newly created role of Global Quality Manager, while Tony Heywood from AB Turnkey Solutions takes over Roys previous position as Production Manager. John Forbes, formerly a senior manager at Thermo Fisher Scientific, joins as Global Service Manager.

ImageOne Medical Former U.S. Olympian Tuesday Middaugh Slomovitz was named COO of Florida-based ImageOne Medical.

Verrica Pharmaceuticals Pennsylvania-based Verrica named two new vice presidents in its commercial operations group. Gerard DiGirolamo joins as head of sales and Sheila Kennedy has been appointed head of marketing. Prior to Verrica, DiGirolamo spent over 16 years with Stiefel, currently a GSK company, in roles of increasing and varying responsibilities, spanning multiple brands within the dermatology space. Kennedy joins Verrica with over 20 years of success as a biopharmaceutical marketing strategist. In her most recent role, Kennedy directed global and U.S. marketing for the dermatology medication Rhofade. In a prior role, Kennedy served as head of marketing for Onset Dermatologics.

TELA Bio Peter Murphy was named to the newly created role of chief commercial officer. In this position, Murphy will be responsible for the companys continued strategic expansion of its commercial operations. Murphy joins TELA with more than 20 years of commercial sales and marketing. Most recently, he was head of sales at Pacira Pharmaceuticals, where he led the development, management, expansion and execution of a product sales team in the U.S.

NuHope -- Jeff Dunkel assumes the role of NuHope CEO following his position as head of strategy at TITAN SPINE.NuHope is a San Antonio-based outpatient opioid and pain treatment center focused on taper effectiveness, which specificallyreduces controlled substance use in those dependent on opioids.

ValueHealth, LLC William J. Hozack was named medical director. In this new role, Hozack will oversee ValueHealth's clinical protocols, quality outcome measures, patient care pathways, and bundled payments with warranty programs. He will also serve as a liaison to ValueHealth's Advisory Board and provide strategic guidance to the company.

Enzychem Lifesciences Liver disease specialist Michael Charlton joined the companys scientific advisory board. Charlton is currently director of the Center for Liver Diseases at University of Chicago School of Medicine. He has served as president of the International Liver Transplant Society.

Disc Medicine John Quisel was named president and CEO of Disc Medicine. Quisel joins Disc Medicine after more than a decade at Acceleron Pharma where he most recently was CBO. In this planned transition, co-founder and interim CEO Brian MacDonald, will continue to serve as a senior advisor and director of the company.

NeoImmuneTech, Inc. -- Gene Namgoong was named COO of Maryland-based NeoImmuneTech, a T cell-focused immunotherapeutics company. As COO, Namgoong will play a key role in advancing its business operations and shaping its corporate culture. Namgoong joined NeoImmuneTech in 2014 as a legal advisor, later assuming the critical role of general counsel in 2016.

SutroVax Jim Wassil was named COO of California-based SutroVax, Inc. Wassil will lead clinical development, regulatory affairs, medical affairs, quality assurance and program management activities. He spent the past three decades in positions of increasing responsibility in the vaccine divisions of Merck, Novartis, and Pfizer. Most recently, he was responsible for market access, policy, pricing, tender negotiations, epidemiology and health outcomes as the business unit lead for Pfizer Vaccines.

Insmed Incorporated -- Sara Bonstein was named CFO of New Jersey-based Insmed. Bonstein will assume responsibility for leading the company's global financial operations. She most recently served as CFO and COO of OncoSec Medical Incorporated. Prior to joining OncoSec, Bonstein served as the CFO at Advaxis, Inc.

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Movers and Shakers, Jan. 31 | BioSpace - BioSpace

Breathing in a New Gene Therapy to treat Pulmonary Hypertension

Newswise (New York, NY July 12, 2017) Mount Sinai has partnered with Theragene Pharmaceuticals, Inc. to advance a novel airway-delivered gene therapy for treating pulmonary hypertension (PH), a form of high blood pressure in blood vessels in the lungs that is linked to heart failure. If the therapy succeeds in human clinical trials, it will provide patients for the first time with a way to reverse the damage caused by PH.

This gene therapy technique comes from the research of Roger J. Hajjar, MD, Professor of Medicine and Director of the Cardiovascular Research Center at the Icahn School of Medicine at Mount Sinai, and has been proven effective in rodent and pig animal models. PH is a deadly disease that disproportionately affects young adults and women; 58 percent of cases are found in young adults and 72 percent are women. There is currently no effective cure for PH, and about 50 percent of people who are diagnosed will die from the disease within five years.

PH is a rare (15-50 cases per million people), rapidly progressing disease that occurs when blood pressure is too high in vessels leading from the heart to the lungs. The high pressure is caused by abnormal remodeling of the lung blood vessels, characterized by a proliferation of smooth muscle cells and a thickening and narrowing of these vessels, and can lead to failure of the right ventricle of the heart and premature death. Abnormalities in calcium cycling within the vascular cells play a key role in the pathophysiology of pulmonary hypertension, along with deficiencies in the sarcoplasmic reticulum calcium ATPase pump (SERCA2a) protein which regulates intracellular calcium within these vascular cells and prevents them from proliferating within the vessel wall. Downregulation of SERCA2a leads to the proliferative remodeling of the vasculature. This gene therapy, delivered via an inhaled aerosolized spray, aims to increase the expression of SERCA2a protein, and has been shown in rodents and pigs to improve heart and lung function, as well as reduce and even reverse cellular changes caused by PH.

This is a devastating disease, and our work in collaboration with many laboratories across the country has allowed us to identify a specific molecular target and use gene therapy to improve cardiovascular and lung parameters in experimental models of PH. We look forward to starting first-in-human studies using this approach in affected patients, said Dr. Hajjar, the senior author of the studies, highlighting that clinical trials will be underway in the next two years.It may take several years before a product is commercially available for PH patients.

We are excited about the potential for SERCA2a gene therapy as a new modality in treating this serious disease, said Jon Berglin, Chief Executive Officer of Theragene Pharmaceuticals, Inc. We look forward to develop and advance this promising product into the clinic.

This represents another critical advancement in a potentially transformative therapeutic breakthrough by Mount Sinai scientists, demonstrating our commitment to improving health outcomes. We are thrilled to be working with Theragene Pharmaceuticals, and continue to strengthen our expertise in partnering health care innovations with industry, said Erik Lium, PhD, Senior Vice President of Mount Sinai Innovation Partners, the commercialization arm of the Icahn School of Medicine at Mount Sinai.

About Mount Sinai Innovation Partners (MSIP)MSIP is responsible for driving the real-world application and commercialization of Mount Sinai discoveries and the development of research partnerships with industry. The aim is to translate these innovations into healthcare products and services that benefit patients and society. MSIP is responsible for the full spectrum of commercialization activities required to bring the Icahn School of Medicine and the Mount Sinai Health Systems inventions to life. These activities include evaluating, patenting, marketing and licensing new technologies, engaging commercial and non-profit relationships for sponsored research, material transfer and confidentiality, as well as fostering an ecosystem of entrepreneurship within our research and health system communities. For more information, visit http://www.ip.mountsinai.org.

About Theragene Pharmaceuticals, Inc.Theragene is a biopharmaceutical company developing cutting-edge science for the treatment of debilitating diseases. The Companys diverse portfolio consists of preclinical and clinical oncology and cardiology platforms utilizing next generation gene therapy and immunotherapy methods.

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Breathing in a New Gene Therapy to Treat Pulmonary Hypertension - Newswise (press release)

METISis a B-corp* founded in April 2017 by the confluence of a handful of scientists, among the leaders of oncogene research, and a group of visionary investors with the mission of translating cancer research findings into precision medicine in cancer treatments.

Backed by over three decades of research focused on a specific oncogene, METIS benefits from a profound knowledge of the biology and pathology driven by the oncogene MET, including cancer.

METIS is developing human anti-MET antibodies with the potential to be first-in class to treat diseases with a significant unmet medical need.

The most advanced anti-MET antibody - hOA-DN30 - has proven to be unique and extremely effective against cancer in pre-clinical setting.

METIS owns the intellectual property of a suite of anti-MET monoclonal antibodies (the Platform), targeting the MET oncogene.

(*) Benefit Corporations or B Corps are companies that voluntarily meet the highest standards of purpose, responsibility, and transparency. They go beyond the goal of profit, and innovate to maximize the positive impact on communities, environment, and mankind.

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METIS Precision Medicine The one gene company

July 12, 2017 by George Lowery Mouse intestinal organoids that scientists genetically engineered to study colon cancer. Using gene editing technology, the investigators fused together the genes Ptprk and Rspo3 to determine their effect on cancer development. Credit: Cornell University

Genetic mutations caused by rearranged chromosomes drive the development and growth of certain colorectal cancers, according to new research conducted by Weill Cornell Medicine investigators.

Many of the genetic mutations present in colorectal cancer have been known for decades. But their exact role in cancer's development and progression has not been clear. "We knew that these mutations existed, but not whether they contribute to the disease," said Lukas Dow, an assistant professor of biochemistry in medicine and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. "So we are interested in whether they are actually driving cancer and whether they can potentially be targets for drugs that treat it."

In a paper published July 11 in Nature Communications, Dow and his colleagues describe how large pieces of chromosomes are deleted or inverted, resulting in new, mutated so-called fusion genes created from parts of two other genes that are responsible for the formation of some colon cancers.

The researchers used the gene editing technology CRISPR, which allows scientists to easily alter any piece of DNA in an organism, to cut the DNA in normal human intestinal cells and create fusion genes. In this way, they engineered the genetic mutations in two genes Rspo2 and Rspo3 known to be associated with colorectal cancer. They then created mice containing these genes to study the genes' effect on colon cancer development.

Though CRISPR has received a lot of attention in the last several years, this is the first time the tool has been used this way. "We created the first CRISPR-based transgenic animal model for inducing large-scale chromosomal rearrangements," Dow said.

These chromosomal rearrangements in the Rspo genes did in fact initiate growth of colon cancer in the mice. The mice containing the engineered genes developed multiple precancerous tumors that are the precursors to colorectal cancer. "This is the first evidence that these specific fusions can drive tumor development," Dow said.

Dow's team went on to treat the mice that developed cancer with an experimental drug, LGK974, which blocks a protein necessary for Rspo fusion genes to cause disease. "The tumors shrank and the mice were fine as long as they continued to take LGK974," Dow said. In addition, the drug only suppressed growth of the cancer cells; it had no obvious negative effect on healthy cells in the mouse intestine.

The study's results hold particular promise for the treatment of colorectal cancer in humans, Dow said. This form of cancer has historically been a difficult disease to treat. Chemotherapy drugs have limited impact against colorectal cancer and developing targeted therapies drugs that target aspects of cancer cells that make them different from healthy cells has proven difficult. "Our results give us confidence that if we can deliver LGK974 effectively to patients with these fusion genes," Dow said, "then we should be able to see some tumor response with these targeted agents."

Explore further: Novel gene editing approach to cancer treatment shows promise in mice

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'Fusion genes' drive formation and growth of colorectal cancer - Medical Xpress

Santa Fe New Mexican

FDA advisers review data on potential 1st US gene therapy Lexington Herald Leader The Food and Drug Administration panel is holding a hearing Wednesday to discuss the treatment developed by the University of Pennsylvania and Novartis Corp. The drugmaker is seeking approval to use the one-time treatment for children and young ... First gene therapy on the cusp of FDA approvalSanta Fe New Mexican all 27 news articles »

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FDA advisers review data on potential 1st US gene therapy - Lexington Herald Leader

South Koreas Ministry of Food and Drug Safety said today that it has approved the countrys first gene therapy for osteoarthritis, the lead product candidate of a Maryland-based regenerative medicine company.

Invossa-K Inj. was developed by Maryland-based TissueGene, whose Korean licensee, Kolon Life Sciences, won approval for the injectable treatment. According to the company, Invossa is a first-in-class cell-mediated gene therapy designed to treat moderate (Kellgren and Lawrence grade 3) knee osteoarthritis through regeneration of cartilage.

Invossa uses allogeneic human cartilage cells engineered to express transforming growth factor TGF-1. TissueGenes platform technology involves transducing the cells with a retroviral vector engineered to express TGF-1 at a specific therapeutic level and duration of time.

The modified cell lines are further selected and screened for cellular expression characteristics intended to minimize patient immune response to the injected cellsthen mixed with unmodified cells to create cartilage regeneration via Invossa, as well as bone, disc, and nerve regeneration through the companys other product candidates.

Invossa is designed for a single injection directly into the knee joint, allowing the cells to induce repair and regeneration of tissue by secreting therapeutic growth factors. The gene therapyincluded in GENs recent roundup of Top Trends in Tissue Engineeringis an alternative to surgery for arthritis patients, according to Kolon.

Kolon has said injection of Invossa has been shown in Phase III trials in Korea to ease the symptoms of about 84% of patientswhile 88% of U.S. patients treated with the gene therapy in Phase 2 trials reported improved symptoms for up to two years.

Invossa is being assessed in a Phase III trial in the U.S. after TissueGene and the FDA came to agreement on a Special Protocol Assessment (SPA) for the study. The company is seeking agency approval for the gene therapy as the first disease-modifying osteoarthritis drug (DMOAD).

Kolon has also inked an exclusive licensing and development agreement with Mitsubishi Tanabe Pharma to market the drug in Japan. Under that deal, Mitsubishi Tanabe agreed to pay approximately $24 million upfront plus up to $410 million in payments tied to achieving development, regulatory, and commercial milestones, plus double-digit sales royalties.

In Korea, Mundipharma plans to market and distribute Invossa to general and semiprivate hospitals, while Kolon focuses on general practitioners, under an agreement announced April 11.

With the Korean drug ministrys approval, Invossa became the 29th South Koreandeveloped novel therapy approved by the countrys drug regulatory agencyand one of only four cell gene therapies to have ever been approved globally. The others were approved to treat immunodeficiency diseases, genetic disorders, and cancer.

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South Korea OKs First-in-Class Gene Therapy for Osteoarthritis - Genetic Engineering & Biotechnology News

Demonstrates broad biodistribution, including across the blood-brain barrier into the central nervous system, and into skeletal muscle, in non-human primates (NHPs) after systemic administration

Durable and therapeutically relevant drug concentrations achieved in NHPs after single intravenous dose

Potent cell-based activity and allele-specific enrichment in patient-derived cell lines

Platform validation data supports expansion of the therapeutic pipeline into new organ systems previously unreachable with first-generation antisense oligonucleotide technology

Management to hold a conference call today at 8 a.m. ET

PITTSBURGH, March 31, 2020 (GLOBE NEWSWIRE) -- NeuBase Therapeutics, Inc. (Nasdaq:NBSE) (NeuBase or the Company), a biotechnology company developing next-generation antisense oligonucleotide (ASO) therapies to address genetic diseases, today announced positive preclinical data from its pharmacokinetics studies in non-human primates (NHPs) and in vitro pharmacodynamics data in patient-derived cell lines. NeuBase believes these data validate the key advantages of the proprietary NeuBase peptide-nucleic acid (PNA) antisense oligonucleotide (PATrOL) platform and support the Companys decision to advance the development of its Huntingtons disease (HD) and myotonic dystrophy type 1 (DM1) programs, as well as the potential expansion of its therapeutic pipeline into other indications.

Dr. George Church, professor of genetics at Harvard Medical School and member of the National Academy of Sciences, stated, Given the activity and broad biodistribution observed in these studies and the potential for easier target definition, I believe the PATrOL technology may have a potent impact on the future of drug development and treatment of genetic diseases.

Non-Human Primate Pharmacokinetic Study

Quantitative whole-body autoradiography was performed on NHPs.A PATrOL-enabled compound was radio-labeled, and theresulting material was injected into NHPs at 5 mg/kg via a bolus tail vein injection. At four hours, twelve hours, and seven days post-dosing, NHPs were sacrificed andsectioned into 40 m slices.Slices were exposed to autoradiography imaging plates alongside a dilution series of radioactive PNA in whole blood.Upon imaging, the dilution series enabled an analysis of the amount of compound in each of the tissues. In addition, prior to sacrifice, whole blood, urine, and feces were collected from the NHPs at specified timepoints.The major conclusions from this study include:

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Rapid uptake of compound out of the bodys circulation after systemic intravenous administration, with a half-life in circulation of approximately 1.5 hours;

Compound penetrates every organ system studied, including the central nervous system and skeletal muscle;

Compound crosses the blood-brain barrier and into the key deep brain structures, including the caudate, supporting a key capability for the development of the Companys lead program in HD; Delivery of the compound to skeletal muscle, the primary organ system that is affected in DM1;Because both HD and DM1 have manifestations outside of the primary affected organ, the broad biodistribution of the compounds may enable a potential whole-body therapeutic solution in both indications.

96% of administered compound remained in vivo after a one-week period (latest timepoint tested);Redistribution over one week after administration between organ systems enriches concentrations in key brain regions up to two-fold, including in those deep brain structures most relevant for HD;Retention of ~90% of compound concentrations achieved in skeletal muscle over the course of one-week post-single-dose administration; and

Patient-Derived Huntingtons Cell Line Pharmacodynamic Studies

Multiple Huntingtons disease candidate compounds were incubated with HD-derived cells and assayed for their toxicity and their ability to selectively knock down mutant huntingtin protein (mHTT) expression by engaging with the CAG repeat expansion in the huntingtin (HTT) gene transcript. Multi-well plates were seeded with cells and candidates were added to the culture at various concentrations.Cells were grown for three days and thereafter assayed for cell death.Cell pellets were also collected, lysed, and run on gradient SDS-PAGE gels.Following the transfer of the proteins to a membrane, the membrane was probed with anti-huntingtin and anti-beta-actin antibodies.Secondary antibodies were used to image the immunoblots.The beta-actin bands were used to normalize the amount of protein across the wells.The amounts of mutant and wild type huntingtin protein in treated cells were compared to untreated cells to determine the level of knockdown.The major conclusions from this study include:

Activity in engaging target disease-causing transcripts and knocking-down resultant malfunctioning mHTT protein levels preferentially over normal HTT protein knock-down; and

Dose limiting toxicities were not observed relative to a control either at or above the doses demonstrating activity in human cells in vitro.

In addition, PATrOL enabled compounds were generally well-tolerated in vivo after systemic administration, both after single dose administration in NHPs and multi dose administration in mice for over a month.

We believe the PATrOL platform has the potential to create drugs that are easy for patients to take at infrequent intervals after they have tested positive for a genetic disease but before symptoms emerge, said Dietrich Stephan, Ph.D., chief executive officer of NeuBase. We believe the best way to effectively manage degenerative genetic diseases is to get ahead of the disease process, and we believe that can only be achieved with early diagnosis coupled with well-tolerated, effective, and easily administered therapies.

Dr. Robert Friedlander, chief medical officer of NeuBase and member of the National Academy of Medicine, stated, An allele specific approach that can be systemically administered and cross the blood brain barrier would be an ideal drug profile for many untreatablegenetic diseases.I believe that NeuBase is moving towards realizing this goal.

The intersection of the NHP pharmacokinetic data and the in vitro patient-derived pharmacodynamic data provides a roadmap to create a pipeline of therapeutic candidates which can reach target tissues of interest after systemic administration and achieve the desired activity at that dose. NeuBase believes the data from these studies support the advancement of the Companys HD and DM1 programs into lead optimization and subsequent IND-enabling studies, as well as provide a roadmap for the future expansion of the Companys therapeutic pipeline into other indications, including oncology.

Dr. Sam Broder, former Director of the National Cancer Institute of the National Institutes of Health and member of the National Academy of Sciences, stated, I believe that the NeuBase strategy of targeting transcripts before they become dangerous mutant proteins has the potential to deliver a dramatic improvement in our collective capabilities to effectively treat a wide range of genetic diseases, including some of the most deadly cancers, by targeting driver mutations and accelerating immunotherapy capabilities.

Conference Call

NeuBase Therapeutics, Inc. will discuss these data and next steps for development during a webcasted conference call with slides today, March 31, 2020, at 8:00 a.m. ET. The live and archived webcast of this presentation can be accessed through the IR Calendar page on the Investors section of the Companys website, http://www.neubasetherapeutics.com. The dial-in details for the call are 877-451-6152 (domestic) or +1-201-389-0879 (international), and conference ID: 13701118. The archived webcasts will be available for approximately 30 days following the presentation date.

About NeuBase Therapeutics

NeuBase Therapeutics, Inc. is developing the next generation of gene silencing therapies with its flexible, highly specific synthetic antisense oligonucleotides. The proprietary NeuBase peptide-nucleic acid (PNA) antisense oligonucleotide (PATrOL) platform is designed to permit the rapid development of targeted drugs, thereby potentially increasing the treatment opportunities for the hundreds of millions of people affected by rare genetic diseases, including those that can only be treated through accessing of secondary RNA structures. Using PATrOL technology, NeuBase aims to first tackle rare, genetic neurological disorders.

Safe Harbor Statement under the Private Securities Litigation Reform Act of 1995

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act. These forward-looking statements include, among other things, statements regarding the Companys goals and plans and the Companys pharmacokinetics and pharmacodynamics studies. These forward-looking statements are distinguished by use of words such as will, would, anticipate, expect, believe, designed, plan, or intend, the negative of these terms, and similar references to future periods. These views involve risks and uncertainties that are difficult to predict and, accordingly, our actual results may differ materially from the results discussed in our forward-looking statements. Our forward-looking statements contained herein speak only as of the date of this press release. Factors or events that we cannot predict, including those described in the risk factors contained in our filings with the U.S. Securities and Exchange Commission, may cause our actual results to differ from those expressed in forward-looking statements. The Company may not actually achieve the plans, carry out the intentions or meet the expectations or projections disclosed in the forward-looking statements, and you should not place undue reliance on these forward-looking statements. Because such statements deal with future events and are based on the Companys current expectations, they are subject to various risks and uncertainties and actual results, performance or achievements of the Company could differ materially from those described in or implied by the statements in this press release, including: the Companys plans to develop and commercialize its product candidates; the Companys plans to commence clinical trials in Huntingtons disease and myotonic dystrophy type 1 and to potentially expand the pipeline into other indications; the utility of the preclinical data generated in existing studies performed by the Company in determining the results of potential future clinical trials and of the potential benefits of the PATrOL platform technology; the timing of initiation of the Companys planned clinical trials; the timing of the availability of data from the Companys clinical trials; the timing of any planned investigational new drug application or new drug application; the Companys plans to research, develop and commercialize its current and potential future product candidates; the clinical utility, potential benefits and market acceptance of the Companys current and potential future product candidates; the Companys commercialization, marketing and manufacturing capabilities and strategy; the Companys ability to protect its intellectual property position; and the requirement for additional capital to continue to advance these product candidates, which may not be available on favorable terms or at all, as well as those risk factors in our filings with the U.S. Securities and Exchange Commission. Except as otherwise required by law, the Company disclaims any intention or obligation to update or revise any forward-looking statements, which speak only as of the date hereof, whether as a result of new information, future events or circumstances or otherwise.

NeuBase Investor Contact:Dan FerryManaging DirectorLifeSci Advisors, LLCDaniel@lifesciadvisors.comOP: (617) 535-7746

NeuBase Media Contact:Travis Kruse, Ph.D.Russo Partners, LLCtravis.kruse@russopartnersllc.comOP: (212) 845-4272

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NeuBase Therapeutics Announces Positive, Preclinical Data Validating its Novel Genetic Therapy PATrOL Platform - Yahoo Finance

Deals and Financings

Nanjing Legend Biotech, a subsidiary of GenScript (HK: 1548) (OTC:GNNSF), has filed for an IPO on a US exchange. In 2017, Legend surprised the world when its CAR-T therapy produced a 94% response rate in pretreated multiple myeloma patients. Six months later, Johnson & Johnson (NYSE:JNJ) partnered the treatment in a deal that paid Legend $350 million upfront, plus unspecified milestones and royalties. The CAR-T candidate, JNJ-4528, is now in Phase II trials in the US.

Harbour BioMed (HBM) raised $75 million in a Series B+ round to advance its clinical-stage compounds and portfolio of next-gen biotherapies for cancer and immunological diseases. The company builds its portfolio by in-licensings and via its proprietary Harbour Mice program. Harbour develops drugs for China and US markets, while it has entered partnerships to discover candidates for China companies Innovent (OTCPK:IVBIY) and BeiGene (NASDAQ:BGNE), along with other prominent global biopharmas. The company previously completed an $85 million Series B financing in August 2018. HBM is headquartered in Cambridge, MA, and it conducts R&D in Suzhou and Shanghai.

GenFleet Therapeutics (Shanghai) closed a $57 million Series B financing, co-led by CDH Investments and Shenzhen Capital Group. Founded in 2017, GenFleet is developing novel large and small therapeutic molecules for oncology and immunology targets. The company says its projects are potential first-in-class therapeutics with technical advantages and large markets. It will use the capital for ex-China development and clinical trials of its existing pipelines, plus expanding its immunology platform, working on new projects and building an industrial base.

Arctic Vision of Shanghai in-licensed greater China rights to Xipere, a treatment for macular edema associated with uveitis, from Clearside Bio (NASDAQ:CLSD) in a $35.5 million agreement. Founded last year, Arctic in-licenses breakthrough ophthalmology products for China. Xipere is its first deal. Arctic plans to acquire China rights to 3-5 products and then expand to a combination of global rights and internal discovery for additional drugs. Clearside, which is located in Alpharetta, Georgia, said Xipere is a proprietary suspension of the corticosteroid triamcinolone acetonide.

Exuma Biotech (formerly F1 Oncology), a Florida-Shanghai company developing CAR-T products for solid tumors, closed a $19 million Series B round. The financing included investments from MSD Partners and F1 BioVentures, plus conversion of notes held by individual investors. Exuma's Logic Gated CAR-T products become activated only when the target antigen and the tumor microenvironment are both present, reducing off-tumor side effects. The company has started clinical trials of two candidates. Exuma's Shanghai subsidiary oversees the company's development, manufacturing, and commercial units in Shanghai and Shenzhen.

OBiO Technology (Shanghai) completed a B+ Round of more than $15 million for its viral-based gene therapy CRO services and genetic drug CDMO/CMO services. Founded in 2013, OBiO collaborated with GE Healthcare (NYSE:GE) to establish the first domestic GMP viral production workshop in China and supply CRO/CDMO/CMO services for viral drugs. At the same time, OBiO is incubating gene therapy drugs for cancer therapy with three ADC candidates for oncotherapy that have proprietary IP. The B+ Round investors included GP Capital, Sinowisdom and Efung Capital.

Shanghai OPM Biosciences raised $14 million from China Life Medical Fund to support its CDMO service platform. The company offers serum-free media for cell cultures based on animal cells, as well as a full-range of cell culture development services. It customizes high-quality personalized animal cell culture media to optimize the cell culture process and reduce production costs. OPM has developed a variety of chemically defined CHO/HEK293 cell culture media and nutritional products. The company claims its media improve cell growth and expression.

China Immunotech Biotech of Beijing completed a $6.5 million Series A financing, led by Jianxin Capital with Grower Venture Capital and Huacheng Group participating. Founded in March 2018, China Immunotech is developing TCR-T and CAR-T products that target hematological tumors, solid tumors and virus-related diseases. It has two unique technology platforms, STAR-T and TCR-T. The STAR-T platform uses a proprietary structure of antigen receptor complexes. The company believes the platform provides multi-targeted molecules with better efficacy, fewer side effects and easier development than traditional CAR-T products.

Chengdu's HitGen has signed a licensing agreement to develop a novel class of drugs for Kaken, a Japanese (TK: 4521) specialty pharma. HitGen has already used its large library of small molecule and macrocyclic compounds to identify potential candidates. Few details were released, but Kaken is known to be concentrating its R&D on inflammation/immunology (dermatitis, rheumatoid arthritis and osteoarthritis), pain relief and fungal infections. One year ago, the two companies formed a similar collaboration, presumably for other targets. HitGen will receive an upfront payment and be eligible to receive preclinical and clinical milestones.

Suzhou Ascentage Pharma (HK: 6855) announced approvals for three clinical studies of APG-2575, a novel Bcl-2 inhibitor, two in the US and one in China. APG-2575 is an oral drug designed to treat several hematologic malignancies by blocking Bcl-2 to restore the normal apoptosis process in cancer cells. According to Ascentage, the candidate is the first China-made Bcl-2 inhibitor to start clinical trials. In its Phase I clinical studies, APG-2575 did not exhibit any dose-limiting toxicity or tumor lysis syndrome (which is commonly associated with other Bcl-2 inhibitors).

Denovo Biopharma, a San Diego-Beijing precision medicine company, has discovered a novel genetic biomarker for depression that it intends to use with DB104, a triple dopamine, serotonin and norepinephrine reuptake inhibitor. The company made the discovery using its proprietary biomarker discovery platform. Denovo licensed DB104 from Albany Molecular Research. Bristol-Myers Squibb (NYSE:BMY) returned the candidate to Albany after two Phase IIb clinical trials in treatment-resistant depression. The biomarker is one of four DeNovo biomarkers aimed at psychiatric use.

I-Mab (NASDAQ:IMAB), a Shanghai clinical-stage biopharma, has started to develop TJM2 (TJ003234) to treat cytokine release syndrome in severe cases of COVID-19. TJM2 is an I-Mab-discovered neutralizing antibody that binds human granulocyte-macrophage colony stimulating factor (GM-CSF), an important cytokine that plays a critical role in acute and chronic inflammation. By binding GM-CSF, TJM2 prevents downstream signaling and target cell activation, inhibiting other inflammatory responses. I-Mab intends to start clinical trials in the US and expand to countries especially hard-hit by COVID-19.

Mesoblast (NSDQ: MESO; ASX: MSB), an Australia-based regenerative medicine company, announced plans to start trials of remestemcel-L, its allogeneic mesenchymal stem cell (MSC) product candidate, in patients with acute respiratory distress syndrome (ARDS) caused by COVID-19. The trial will be conducted in the US, Australia, China and Europe. ARDS is the principal cause of death in COVID-19 patients. In a small China trial, allogeneic MSCs cured or significantly improved all seven patients with severe COVID-19 pneumonia.

Ascletis (HK: 1672), a Hangzhou biopharma, reported that an initial group of 11 COVID-19 patients all recovered after being treated with a combination Ganovo and Ritonavir therapy. Ascletis's Ganovo, the first approved direct-acting anti-viral agent developed by a China company, was launched in 2018 to treat hepatitis C. Ritonavir is a generic anti-retroviral that is used in AIDS/HIV combination therapies. The small clinical trial was led by Dr. Hongyi Chen, the director of the Ninth Hospital of Nanchang.

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Week In Review: Nanjing Legend Files To Stage IPO In The U.S. - Seeking Alpha

In pulmonary arterial hypertension (PAH), high blood pressure in the lungs arteries causes the heart to work extra hard to pump blood to the lungs and around the rest of the body. The condition is rare but deadly, and current treatments are expensive and have side effects and inconvenient modes of delivery. There is no cure.

With a goal of developing a more effective, convenient, and affordable therapy, research led by Henry Daniell of Penns School of Dental Medicine produced a protein drug in lettuce leaves to treat PAH. He worked with other scientists, including Steven M. Kawut of Penns Perelman School of Medicine; Tim Lahm from the Indiana University School of Medicine; Maria Arolfo and Hanna Ng of the Stanford Research Institute, on toxicology and pharmacokinetic studies; and Cindy McClintock and Diana Severynse-Stevens of RTI International, on regulatory studies.

The protein drug, composed of the enzyme angiotensin converting enzyme-2 (ACE2) and its protein product angiotensin (1-7), can be taken orally and, in an animal model of PAH, reduced pulmonary artery pressure and remodeling. In addition, rigorous toxicology and dose-response studies suggested the drugs safety in animals. Further work will be necessary to develop this novel treatment approach for patients with PAH. The teams findings appear in the March issue of the journal Biomaterials.

We completed extensive investigations to highly express these proteins in lettuce plants and to ensure the product is safe and effective, says Daniell. Were ready to progress with further work to move this to the clinic.

Daniell has employed his innovative platform to grow biomedically important proteins of many kinds in the leaves of plants. The system works by physically bombarding plant tissue with the genes of interest, prompting chloroplasts into taking up genes and then stably expressing that protein. Propagating those plants then creates a kind of pharmaceutical farm from which the researchers can harvest, dry, and process the leaves, resulting in a powder that can be placed in a capsule or suspended in a liquid for use as an oral medication.

A 2014 publication in the journal Hypertension, on which the current study was based, earned Daniell a prize from the American Heart Association, and support from the National Institutes of Health through its Science Moving TowArds Research Translation and Therapy (SMARTT) program, which aims to efficiently translate promising basic science discoveries into therapies that can make a difference in peoples lives.

That earlier publication had shown that ACE2 and angiotensin (1-7) could be expressed in tobacco leaves and, when fed to rats with a condition that models pulmonary arterial hypertension, could significantly reduce the animals pulmonary artery pressure while also improving cardiac function.

To create a drug that humans could safely ingest, however, required moving from a tobacco to a lettuce-based platform. The new work takes advantage of other advancements the Daniell lab has made during the last several years. He and colleagues have successfully devised methods to enhance expression of human genes in the plants and to remove the antibiotic resistance gene that is used to select for angiotensin-producing plants. Theyve also worked with a partner to produce genetically engineered plants in a production facility that adheres to FDA standards.

In the current work, the researchers demonstrated that they could accurately evaluate the dose of the ACE2 and angiotensin (1-7) proteins in lettuce, and that the products could be dried and kept shelf stable for as long as two years.

Funding from the SMARTT program enabled animal studies evaluating toxicology, pharmacodynamic, and pharmacokinetic studies, which evaluate the safety of the drug, where it goes in the body, and how long it persists in the body at different doses, in work done at Stanford University.

And to confirm that the lettuce formulation of the product had a positive impact on experimental PAH, the team fed rats a solution containing the drug for four weeks. Their lung pressures went down 30-50%, and the structure of their arteries also improved.

This is an innovative approach to targeting the renin-angiotensin-aldosterone system in pulmonary arterial hypertension, says Penn Medicines Kawut, which may hold promise in this and other diseases.

We are very excited about this work that shows efficacy of bioencapsulated ACE2 and angiotensin (1-7) in our animal model of pulmonary arterial hypertension, says Indiana Universitys Lahm. We now need to confirm that the intervention also works in other animal models and when given later in the disease. Ultimately, our goal is to move this to the clinic for trials in patients, but we need to make sure we learn as much as possible from animal studies and from studies in healthy human subjects to make sure this intervention is safe and efficacious in patients.

In other future work, Daniell hopes to continue evaluating the effects of ACE2 and angiotensin (1-7) in treating different types of cardiovascular disease, such as heart failure.

There are some potentially broad applications of this drug that were hoping to investigate, says Daniell.

Daniell, Kawut, and Lahms coauthors on the paper were Penn Dental Medicines Venkata Mangu, Jiyoung Park, Peyman Habibi, Yao Shi, and Patricia A. Gonnella; and Indiana Universitys Bakhtiyor Yakubov, Amanda Fisher, Todd Cook, and Lily Zeng.

Henry Daniell is vice chair and W.D. Miller Professor in the Department of Basic & Translational Sciences in the University of Pennsylvania School of Dental Medicine.

Steven M. Kawut is professor of medicine and director of the Pulmonary Vascular Disease Program at the University of Pennsylvania Perelman School of Medicine.

Funding for the study came from the National Institutes of Health (NIH) (grants HL107904, HL109442, and HL133191) and through the NIHs Science Moving TowArds Research Translation and Therapy (SMARTT) program (contracts HHSN268201600011C and HHSN268201600014C).

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Advancing an oral drug for pulmonary arterial hypertension - Penn: Office of University Communications

When you first meet her, you wont be able to tell that Ipek Kuzu suffers from a rare genetic disease. The three-year-old plays happily on her own for hours, driving her toy cars and cooking in her pretend kitchen. But shes not well. Shes a little wobbly on her feet and doesnt say much, and if nothing is done, she may die by her mid-20s. Ipek has ataxia-telangiectasia, or A-T, a disease caused by an error in her DNA. It causes the loss of brain cells, along with a high risk of infection and cancer.

Its the sort of problem that makes doctors shake their heads. But Ipeks father, Mehmet, and mother, Tugba, hope shell escape that fate. Thanks in part to the persistence of Mehmet, a programmer at Google, in January she became one of the first handful of US patients to receive a hyper-personalized gene medicine, tailored to treat a unique mutation. The one-person drug, designed for her by a Boston doctor, Timothy Yu, is being called atipeksen, for A-T and Ipek.

To create atipeksen, Yu borrowed from recent biotech successes like gene therapy. Some new drugs, including cancer therapies, treat disease by directly manipulating genetic information inside a patients cells. Now doctors like Yu find they can alter those treatments as if they were digital programs. Change the code, reprogram the drug, and theres a chance of treating many genetic diseases, even those as unusual as Ipeks.

The new strategy could in theory help millions of people living with rare diseases, the vast majority of which are caused by genetic typos and have no treatment. US regulators say last year they fielded more than 80 requests to allow genetic treatments for individuals or very small groups, and that they may take steps to make tailor-made medicines easier to try. New technologies, including custom gene-editing treatments using CRISPR, are coming next.

Where it had taken decades for Ionis to perfect its drug, Yu now set a record: it took only eight months for Yu to make milasen, try it on animals, and convince the US Food and Drug Administration to let him inject it into Milas spine.

I never thought we would be in a position to even contemplate trying to help these patients, says Stanley Crooke, a biotechnology entrepreneur and founder of Ionis Pharmaceuticals, based in Carlsbad, California. Its an astonishing moment.

Antisense drug

Right now, though, insurance companies wont pay for individualized gene drugs, and no company is making them (though some plan to). Only a few patients have ever gotten them, usually after heroic feats of arm-twisting and fundraising. And its no mistake that programmers like Mehmet Kuzu, who works on data privacy, are among the first to pursue individualized drugs. As computer scientists, they get it. This is all code, says Ethan Perlstein, chief scientific officer at the Christopher and Dana Reeve Foundation.

A nonprofit, the A-T Childrens Project, funded most of the cost of designing and making Ipeks drug. For Brad Margus, who created the foundation in 1993 after his two sons were diagnosed with A-T, the change between then and now couldnt be more dramatic. Weve raised so much money, weve funded so much research, but its so frustrating that the biology just kept getting more and more complex, he says. Now, were suddenly presented with this opportunity to just fix the problem at its source.

Ipek was only a few months old when her father began looking for a cure. A geneticist friend sent him a paper describing a possible treatment for her exact form of A-T, and Kuzu flew from Sunnyvale, California, to Los Angeles to meet the scientists behind the research. But they said no one had tried the drug in people: We need many more years to make this happen, they told him.

Courtesy Photo (Yu)

Kuzu didnt have years. After he returned from Los Angeles, Margus handed him a thumb drive with a video of a talk by Yu, a doctor at Boston Childrens Hospital, who described how he planned to treat a young girl with Batten disease (a different neurodegenerative condition) in what press reports would later dub a stunning illustration of personalized genomic medicine. Kuzu realized Yu was using the very same gene technology the Los Angeles scientists had dismissed as a pipe dream.

That technology is called antisense. Inside a cell, DNA encodes information to make proteins. Between the DNA and the protein, though, come messenger molecules called RNA that ferry the gene information out of the nucleus. Think of antisense as mirror-image molecules that stick to specific RNA messages, letter for letter, blocking them from being made into proteins. Its possible to silence a gene this way, and sometimes to overcome errors, too.

Though the first antisense drugs appeared 20 years ago, the concept achieved its first blockbuster success only in 2016. Thats when a drug called nusinersen, made by Ionis, was approved to treat children with spinal muscular atrophy, a genetic disease that would otherwise kill them by their second birthday.

Yu, a specialist in gene sequencing, had not worked with antisense before, but once hed identified the genetic error causing Batten disease in his young patient, Mila Makovec, it became apparent to him he didnt have to stop there. If he knew the gene error, why not create a gene drug? All of a sudden a lightbulb went off, Yu says. Couldnt one try to reverse this? It was such an appealing idea, and such a simple idea, that we basically just found ourselves unable to let that go.

Yu admits it was bold to suggest his idea to Milas mother, Julia Vitarello. But he was not starting from scratch. In a demonstration of how modular biotech drugs may become, he based milasen on the same chemistry backbone as the Ionis drug, except he made Milas particular mutation the genetic target. Where it had taken decades for Ionis to perfect a drug, Yu now set a record: it took only eight months for him to make milasen, try it on animals, and convince the US Food and Drug Administration to let him inject it into Milas spine.

Whats different now is that someone like Tim Yu can develop a drug with no prior familiarity with this technology, says Art Krieg, chief scientific officer at Checkmate Pharmaceuticals, based in Cambridge, Massachusetts.

Source code

As word got out about milasen, Yu heard from more than a hundred families asking for his help. Thats put the Boston doctor in a tough position. Yu has plans to try antisense to treat a dozen kids with different diseases, but he knows its not the right approach for everyone, and hes still learning which diseases might be most amenable. And nothing is ever simpleor cheap. Each new version of a drug can behave differently and requires costly safety tests in animals.

Kuzu had the advantage that the Los Angeles researchers had already shown antisense might work. Whats more, Margus agreed that the A-T Childrens Project would help fund the research. But it wouldnt be fair to make the treatment just for Ipek if the foundation was paying for it. So Margus and Yu decided to test antisense drugs in the cells of three young A-T patients, including Ipek. Whichever kids cells responded best would get picked.

Matthew Monteith

While he waited for the test results, Kuzu raised about $200,000 from friends and coworkers at Google. One day, an email landed in his in-box from another Google employee who was fundraising to help a sick child. As he read it, Kuzu felt a jolt of recognition: his coworker, Jennifer Seth, was also working with Yu.

Seths daughter Lydia was born in December 2018. The baby, with beautiful chubby cheeks, carries a mutation that causes seizures and may lead to severe disabilities. Seths husband Rohan, a well-connected Silicon Valley entrepreneur, refers to the problem as a tiny random mutation in her source code. The Seths have raised more than $2 million, much of it from co-workers.

Custom drug

By then, Yu was ready to give Kuzu the good news: Ipeks cells had responded the best. So last September the family packed up and moved from California to Cambridge, Massachusetts, so Ipek could start getting atipeksen. The toddler got her first dose this January, under general anesthesia, through a lumbar puncture into her spine.

After a year, the Kuzus hope to learn whether or not the drug is helping. Doctors will track her brain volume and measure biomarkers in Ipeks cerebrospinal fluid as a readout of how her disease is progressing. And a team at Johns Hopkins will help compare her movements with those of other kids, both with and without A-T, to observe whether the expected disease symptoms are delayed.

One serious challenge facing gene drugs for individuals is that short of a healing miracle, it may ultimately be impossible to be sure they really work. Thats because the speed with which diseases like A-T progress can vary widely from person to person. Proving a drug is effective, or revealing that its a dud, almost always requires collecting data from many patients, not just one. Its important for parents who are ready to pay anything, try anything, to appreciate that experimental treatments often dont work, says Holly Fernandez Lynch, a lawyer and ethicist at the University of Pennsylvania. There are risks. Trying one could foreclose other options and even hasten death.

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Kuzu says his family weighed the risks and benefits. Since this is the first time for this kind of drug, we were a little scared, he says. But, he concluded, theres nothing else to do. This is the only thing that might give hope to us and the other families.

Another obstacle to ultra-personal drugs is that insurance wont pay for them. And so far, pharmaceutical companies arent interested either. They prioritize drugs that can be sold thousands of times, but as far as anyone knows, Ipek is the only person alive with her exact mutation. That leaves families facing extraordinary financial demands that only the wealthy, lucky, or well connected can meet. Developing Ipeks treatment has already cost $1.9 million, Margus estimates.

Some scientists think agencies such as the US National Institutes of Health should help fund the research, and will press their case at a meeting in Bethesda, Maryland, in April. Help could also come from the Food and Drug Administration, which is developing guidelines that may speed the work of doctors like Yu. The agency will receive updates on Mila and other patients if any of them experience severe side effects.

The FDA is also considering giving doctors more leeway to modify genetic drugs to try in new patients without securing new permissions each time. Peter Marks, director of the FDAs Center for Biologics Evaluation and Research, likens traditional drug manufacturing to factories that mass-produce identical T-shirts. But, he points out, its now possible to order an individual basic T-shirt embroidered with a company logo. So drug manufacturing could become more customized too, Marks believes.

Custom drugs carrying exactly the message a sick kids body needs? If we get there, credit will go to companies like Ionis that developed the new types of gene medicine. But it should also go to the Kuzusand to Brad Margus, Rohan Seth, Julia Vitarello, and all the other parents who are trying save their kids. In doing so, they are turning hyper-personalized medicine into reality.

Erika Check Hayden is director of the science communication program at the University of California, Santa Cruz.

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If DNA is like software, can we just fix the code? - MIT Technology Review

Kiyohiro Yamazaki,1 Yuta Yoshino,1 Kentaro Kawabe,1 Tomomasa Ibuki,1 Shinichiro Ochi,1 Yoko Mori,1 Yuki Ozaki,1 Shusuke Numata,2 Jun-ichi Iga,1 Tetsuro Ohmori,2 Shu-ichi Ueno1

1Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan; 2Department of Psychiatry, Course of Integrated Brain Sciences, Medical Informatics, Institute of Health Biosciences, the University of Tokushima Graduate School, Tokushima 770-8503, Japan

Correspondence: Jun-ichi IgaDepartment of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, JapanTel +81-89-960-5315Fax +81-89-960-5317Email iga.junichi.it@ehime-u.ac.jp

Introduction: Although ATP-binding cassette sub-family A member 7 gene (ABCA7) is known to be associated with Alzheimers disease, the relationship between ABCA7 and schizophrenia has been unknown.Methods: Schizophrenia patients (n = 50; 24 males, 62.1 0.50 years old) and age- and sex-matched healthy controls (n = 50) were recruited for the mRNA analysis. Additionally, a case-control study for the rs3764650 genotypes was performed with 1308 samples (control subjects; n = 527, schizophrenia patients; n = 781). All participants were Japanese, unrelated to each other, and living in the same area.Results: The distributions of the rs3764650 genotypes in schizophrenia patients were not different from that of controls. However, the ABCA7 mRNA expression levels in schizophrenia patients were significantly higher than those in controls by a logistic regression analysis. Additionally, the ABCA7 mRNA expression levels in schizophrenia patients were correlated with the rs3764650 genotypes in a dose-dependent manner.Discussion: The ABCA7 mRNA expression levels in peripheral blood with the rs3764650 genotypes may be related to pathological mechanisms in schizophrenia and may be a biological marker for schizophrenia.

Keywords: schizophrenia, ATP-binding cassette sub-family A member 7 gene, single nucleotide polymorphism, rs3764650, mRNA expression

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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ABCA7 Gene Expression and Genetic Association Study in Schizophrenia | NDT - Dove Medical Press

AI is rocking medical diagnosis with its potential to incite drastic improvements to hospital processes. AI can process images and patient health records with more accuracy and expediency than humans are capable of, lessening physician workload, reducing misdiagnosis, and empowering clinical staff to provide more value.

While early moving hospitals are already extracting value from AI in medical diagnosis, most US hospitals are at the very early stage of the AI transformation curve - and they risk falling behind if they don't move now.

In this report, Business Insider Intelligence examines the value of AI applications in three high-value areas of medical diagnosis - imaging, clinical decision support, and personalized medicine - to illustrate how the tech can drastically improve patient outcomes, lower costs, and increase productivity.

We look at US health systems that have effectively applied AI in these use cases to illustrate where and how providers should implement AI. Finally, we examine how a leading US health system validates AI partners and internally organizes its AI strategy to offer provider organizations a template for AI innovation.

The companies mentioned in this report are: Aidoc, Allscripts, Amazon, Arterys, Boston Gene, Cabell Huntington Hospital, Cerner, Cleveland Clinic, Epic, Geisinger Health System, Google, HCA Healthcare, IBM, iCAD, IDx, Intermountain Healthcare, Johns Hopkins, Meditech, Microsoft, Mount Sinai, NorthShore University HealthSystem, Oak Street Health, Stanford University, Tempus, UCI Health System, Unanimous AI, Verily, Viz.ai, and Yale New Haven Hospital.

Here are some of the key takeaways from the report:

In full, the report:

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AI IN MEDICAL DIAGNOSIS: How top US health systems are reacting to the disruptive force of AI by revolutionizi - Business Insider India

Chemical nerve agents are some of the most horrifying tools of war today. The compounds kill by paralyzing the nervous system and have been used in devastating attacks on civilians or soldiers in war zones. And they can appear, albeit in smaller doses, in pesticides used in developing countries, endangering farm workers after prolonged exposure.

For years, researchers have been searching for antidotes or treatments that could save those afflicted by these deadly chemicals. In a paper out today in Science Translational Medicine, a team from the U.S. Army Medical Research Institute of Chemical Defense has announced a potential solution: a gene therapy that grants immunity to the effects of nerve agents like sarin.

Nerve agents are compounds that interfere with a persons nervous system. As the chemicals pass through a body after exposure to skin or through inhalation, they disable an enzyme called acetylcholinesterase thats needed for communication between neurons. The results are devastating: An affected person will involuntarily discharge tears, saliva, urine and feces, experience seizures and paralysis, and rapidly die from asphyxiation.

Scientists have found that that certain enzymes in the body called bioscavengers find and break down the toxic nerve agent molecules in the body, disabling them and preventing harm. In earlier work, the Maryland-based team found that a certain variation of a enzyme made in the liver called PON1 was particularly effective. When injected into a mouse, it granted immunity to nerve agents effects temporarily. But now the team has used a gene therapy to coax the body to make the enzyme, continually, on its own.

In the new study, the team focused on a gene that carries the instructions for the most potent version of the PON1 enzyme, called PON1-IF11. By putting the gene into a virus a common technique used to deliver a gene to a host they were able to successfully introduce PON1-IF11 into mice. After injecting the rodents, just once, with the viral vector containing the gene, the mice became immune to the common nerve agents tabun, sarin, cyclosarin and soman.

The results were encouraging. "[I felt] great satisfaction and excitement," said Venkaiah Betapudi, a molecular cell biologist and first author of the paper, in an email. "[I'm] anxious to take this work to next level and make this modern medicine available to our soldiers."

The immunity lasted for the full 5 months of the study, but in theory, it should last for the lifetime of the animal.

As long as the animal lives, the enzyme is there," says Nageswararao Chilukuri, who leads the research group. "We stopped [the study] at five months after the injection, but if we had measured 6 months, 7 months, 8 months I think it will be there. We just dont have the data to show it.

But Chilukuri emphasizes that were a long way from seeing anything close to a nerve agent vaccine for humans that uses the new technique.

Gene therapy products are only for diseases right now, he explains. We are trying to use this for healthy people. We dont know the long-term safety profile of the viral vectors. We have to be absolutely sure that when we inject a virus, that 50 years from now it will not be toxic or cause any complications.

But when it does come of age, it could have broad applications. "This modern medicine can protect sniffing dogs in the battlefield and TSA and border security operations," says Betapudi.

Luckily, many researchers studying gene therapy more broadly are asking these questions too, so answers may soon emerge regarding the safety of this type of gene therapy.

[Editor's note: This post has been updated to include comments from Venkaiah Betapudi, and to clarify the respective contributions of Nageswararao Chilukuri and Betapudi.]

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New Gene Therapy In Mice Could Offer Lasting Protection Against Nerve Agents - Discover Magazine