Category Archives: Gene Medicine

NEW YORK, April 25, 2022 (GLOBE NEWSWIRE) -- Xalud Therapeutics, a clinical-stage biotechnology company developing DNA-delivered therapeutics, today announced the appointment of Amy Chappell, M.D., as an independent strategic advisor. Dr. Chappell will work with Xalud senior management and other advisors to provide strategic input and direction for Xaluds R&D programs, including XT-150, a nonviral DNA-based delivery platform with potential for a broad number of indications.

Amys experience as a physician-scientist, especially with respect to her expertise in pain, will be invaluable to Xalud as we continue to develop XT-150 and advance our novel therapeutic platform for the treatment of chronic inflammatory disorders, which are often accompanied by pain, said Diem Nguyen, Ph.D., MBA, chief executive officer of Xalud.

Dr. Chappell has more than 30 years of experience planning, designing and implementing all stages of clinical trials in neurosciences with expertise in pain, migraine and epilepsy. Dr. Chappell serves on the scientific advisory board of Pinteon Therapeutics, is an adjunct clinical associate professor at the Indiana University School of Medicine and is a fellow of the American Academy of Neurology (FAAN). She spent over 25 years at Eli Lilly and Company, where she started as an associated clinical research physician and took on roles of increasing responsibility until her retirement in 2014 as a senior medical fellow. Dr. Chappell earned her B.S. in biology from Antioch College and her M.D. from Indiana University School of Medicine.

I believe that Xaluds DNA-delivered therapeutic approach holds significant promise for treating a range of inflammatory disorders, Dr. Chappell noted. Im grateful for the opportunity to influence the clinical development of the companys innovative therapies.

About Xalud TherapeuticsXalud Therapeutics is a biotechnology company developing a DNA-delivered therapy platform to treat pathologic inflammation through immune modulation. The company is harnessing the power of interleukin-10 (IL-10), a potent cytokine that acts as a master regulator for multiple inflammatory pathways, to address the root cause of inflammation and subsequently restore homeostasis in the immune system. Xaluds lead product candidate, XT-150, is a locally injectable plasmid DNA gene therapy expressing IL-10v, a proprietary modified variant of IL-10, that addresses pathologic inflammation and pain.

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Kara Stephens-WeaverLifeSci CommunicationsKstephens-weaver@lifescicomms.com407-765-1185

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Xalud Therapeutics Adds Amy Chappell, MD, as a Strategic Advisor - BioSpace

Newswise Experts from the University of Nottingham have developed a ground-breaking software, which combines DNA sequencing and machine learning to help them find where, and to what extent, antibiotic resistant bacteria is being transmitted between humans, animals and the environment.

The study, which is published inPLOS Computational Biology, was led by Dr Tania Dottorini from the School of Veterinary Medicine and Science at the University.

Anthropogenic environments (spaces created by humans), such as areas of intensive livestock farming, are seen as ideal breeding grounds for antimicrobial-resistant bacteria and antimicrobial resistant genes, which are capable of infecting humans and carrying resistance to drugs used in human medicine. This can have huge implications for how certain illnesses and infections can be treated effectively.

China has a large intensive livestock farming industry, poultry being the second most important source of meat in the country, and is the largest user of antibiotics for food production in the world.

In this new study, a team of experts looked at a large scale commercial poultry farm in China, and collected 154 samples from animals, carcasses, workers and their households and environments. From the samples, they isolated a specific bacteria calledEscherichia coli (E. coli).These bacteria can live quite harmlessly in a persons gut, but can also be pathogenic, and genome carry resistance genes against certain drugs, which can result in illness including severe stomach cramps, diarrhoea and vomiting.

Researchers used a computational approach that integrates machine learning, whole genome sequencing, gene sharing networks and mobile genetic elements, to characterise the different types of pathogens found in the farm. They found that antimicrobial genes (genes conferring resistance to the antibiotics) were present in both pathogenic and non-pathogenic bacteria.

The new approach, using machine learning, enabled the team to uncover an entire network of genes associated with antimicrobial resistance, shared across animals, farm workers and the environment around them. Notably, this network included genes known to cause antibiotic resistance as well as yet unknown genes associated to antibiotic resistance.

Dr Dottorini said: We cannot say at this stage where the bacteria originated from, we can only say we found it and it has been shared between animals and humans. As we already know there has been sharing, this is worrying, because people can acquire resistances to drugs from two different ways - from direct contact with an animal, or indirectly by eating contaminated meat. This could be a particular problem in poultry farming, as it is the most widely used meat in the world.

The computational tools that we have developed will enable us to analyse large complex data from different sources, at the same time as identifying where hotspots for certain bacteria may be. They are fast, they are precise and they can be applied on large environments for instance multiple farms at the same time.

There are many antimicrobial resistant genes we already know about, but how do we go beyond these and unravel new targets to design new drugs?

Our approach, using machine learning, opens up new possibilities for the development of fast, affordable and effective computational methods that can provide new insights into the epidemiology of antimicrobial resistance in livestock farming.

The research was done in collaboration with Professor Junshi Chen, Professor Fengqin Li and Professor Zixin Peng from China National Center for Food Safety Risk Assessment (CFSA).

The full study can be foundhere.

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Scientists use machine learning to identify antibiotic resistant bacteria that can spread between animals, humans and the environment - Newswise

-Approximately 500 Canadians ages 6-11 are now eligible for PrTRIKAFTA-

-Vertex has submitted this indication to CADTH & INESSS for Health Technology Assessments-

TORONTO, April 20, 2022 /CNW/ - Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that Health Canada has granted Marketing Authorization for the expanded use of PrTRIKAFTA (elexacaftor/tezacaftor/ivacaftor and ivacaftor) to include children with cystic fibrosis (CF) ages 6 through 11 years who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. With this announcement, approximately 500 Canadians with CF ages 6-11 are now eligible for TRIKAFTA. As a result of this approval, an additional dosage strength of TRIKAFTA tablets is now available (elexacaftor 50 mg/tezacaftor 25 mg/ivacaftor 37.5 mg and ivacaftor 75 mg).

Vertex Pharmaceuticals (Canada) Inc. Logo (CNW Group/Vertex Pharmaceuticals (Canada) Inc.)

"We are delighted that TRIKAFTA is now available for these young patients in Canada. It provides a new treatment option for those with CF ages 6-11 with at least one F508del mutation and a first-in-class treatment option for the approximately 500 6-11-year-olds who are newly eligible for a medicine that treats the underlying cause of their disease," said Reshma Kewalramani, M.D., Chief Executive Officer and President at Vertex. "This important milestone brings us one step closer to our ultimate goal of developing treatments for all patients living with CF. We will now work closely with all provinces and territories to secure access for eligible patients as quickly as possible."

Vertex completed a 24-week Phase 3 open-label, multicenter study which enrolled 66 children ages 6 through 11 years old with CF who have either two copies of the F508del mutation or one copy of the F508del mutation and one minimal function mutation to evaluate the safety, pharmacokinetics and efficacy of TRIKAFTA. The regimen was generally well tolerated, and safety data were consistent with those observed in previous studies in patients ages 12 years and older.

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"As a trial investigator, I have seen firsthand the demonstrated efficacy of TRIKAFTA in people ages 6-11 living with cystic fibrosis," said Larry C. Lands, M.D., Ph.D., Director, Pediatric Respiratory Medicine, Pediatric Cystic Fibrosis Clinic, and Pediatric Pulmonary Function Laboratory, Montreal Children's Hospital, McGill University Health Center, and Professor, Department of Pediatrics, Faculty of Medicine, McGill University. "This is an exciting next step that will allow eligible patients to begin treatment earlier."

Vertex has also submitted this indication to both the Canadian Agency for Drugs and Technologies in Health (CADTH) and the Institut national d'excellence en sant et en services sociaux (INESSS) in Qubec for Health Technology Assessments.

About Cystic Fibrosis

Cystic fibrosis (CF) is a rare, life-shortening genetic disease affecting more than 83,000 people globally. CF is a progressive, multi-organ disease that affects the lungs, liver, pancreas, GI tract, sinuses, sweat glands and reproductive tract. CF is caused by a defective and/or missing CFTR protein resulting from certain mutations in the CFTR gene. Children must inherit two defective CFTR genes one from each parent to have CF, and these mutations can be identified by a genetic test. While there are many different types of CFTR mutations that can cause the disease, the vast majority of people with CF have at least one F508del mutation. CFTR mutations lead to CF by causing CFTR protein to be defective or by leading to a shortage or absence of CFTR protein at the cell surface. The defective function and/or absence of CFTR protein results in poor flow of salt and water into and out of the cells in a number of organs. In the lungs, this leads to the buildup of abnormally thick, sticky mucus, chronic lung infections and progressive lung damage that eventually leads to death for many patients. The median age of death is in the early 30s.

About PrTRIKAFTA (elexacaftor/tezacaftor/ivacaftor and ivacaftor)

In people with certain types of mutations in the CFTR gene, the CFTR protein is not processed or folded normally within the cell, and this can prevent the CFTR protein from reaching the cell surface and functioning properly. PrTRIKAFTA (elexacaftor/tezacaftor/ivacaftor and ivacaftor) is an oral medicine designed to increase the quantity and function of the CFTR protein at the cell surface. Elexacaftor and tezacaftor work together to increase the amount of mature protein at the cell surface by binding to different sites on the CFTR protein. Ivacaftor, which is known as a CFTR potentiator, is designed to facilitate the ability of CFTR proteins to transport salt and water across the cell membrane. The combined actions of elexacaftor, tezacaftor and ivacaftor help hydrate and clear mucus from the airways. TRIKAFTA is a prescription medicine used for the treatment of cystic fibrosis (CF) in patients ages 6 years and older who have at least one copy of the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

About Vertex

Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases. The company has multiple approved medicines that treat the underlying cause of cystic fibrosis (CF) a rare, life-threatening genetic disease and has several ongoing clinical and research programs in CF. Beyond CF, Vertex has a robust pipeline of investigational small molecule, cell and genetic therapies in other serious diseases where it has deep insight into causal human biology, including sickle cell disease, beta thalassemia, APOL1-mediated kidney disease, pain, type 1 diabetes, alpha-1 antitrypsin deficiency and Duchenne muscular dystrophy.

Founded in 1989 in Cambridge, Mass., Vertex's global headquarters is now located in Boston's Innovation District and its international headquarters is in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia and Latin America. Vertex is consistently recognized as one of the industry's top places to work, including 12 consecutive years on Science magazine's Top Employers list and one of the 2021 Seramount (formerly Working Mother Media) 100 Best Companies. For company updates and to learn more about Vertex's history of innovation, visit http://www.vrtx.com or follow us on Facebook, Twitter, LinkedIn, YouTube and Instagram.

Special Note Regarding Forward-Looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements made by Dr. Kewalramani and Dr. Lands in this press release, and statements regarding the estimated number of children eligible for TRIKAFTA for the first time, our beliefs regarding the benefits of our medicines, and anticipated patient access to TRIKAFTA. While Vertex believes the forward-looking statements contained in this press release are accurate, these forward-looking statements represent the company's beliefs only as of the date of this press release and there are a number of risks and uncertainties that could cause actual events or results to differ materially from those expressed or implied by such forward-looking statements. Those risks and uncertainties include, among other things, that data from the company's development programs may not support registration or further development of its compounds due to safety, efficacy, or other reasons, and other risks listed under the heading "Risk Factors" in Vertex's most recent annual report and subsequent quarterly reports filed with the Securities and Exchange Commission at http://www.sec.gov and available through the company's website at http://www.vrtx.com. You should not place undue reliance on these statements or the scientific data presented. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.

(VRTX-GEN)

SOURCE Vertex Pharmaceuticals (Canada) Inc.

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Health Canada Grants Marketing Authorization for TRIKAFTA (elexacaftor/tezacaftor/ivacaftor and ivacaftor) in Children With Cystic Fibrosis Ages 6...

Cell culture, virus, and plasmids

The human kidney cell line (HEK293) used in this study was obtained and cultured as previously described14,15. The swine kidney line L (SK-L) cells were propagated in Eagles Minimum Essential Medium (Nissui Pharmaceutical, Tokyo, Japan) supplemented with 0.3mg/mL l-glutamine (Nacalai Tesque, Kyoto, Japan), 100 U/mg penicillin G (Meiji Seika Pharma, Tokyo, Japan), 8mg/mL gentamycin (TAKATA Pharmaceutical, Saitama, Japan), sodium bicarbonate (Nacalai Tesque), 0.1mg/mL streptomycin (Meiji Seika Pharma), 0.295% tryptose phosphate broth (Becton Dickinson and Company, Franklin Lakes, NJ, USA), 10mMN,N-bis-(2-hydroxyethyl)-2-aminoethanesulfonic acid (BSE; MilliporeSigma, St. Louis, MO, USA), and 10% horse serum (Thermo Fisher Scientific, Waltham, MA, USA).

The vCSFV GPE-/HiBiT recombinant classical swine fever virus encoding the HiBit luciferase gene16 was derived from the recombinant full-length cDNA of the CSFV GPE-strain17. SK-L cells were infected with tenfold serially diluted vCSFV GPE-HiBiT in 96-well plates and incubated at 37C for 3 days. Virus growth was analyzed using luciferase activity as an indicator. Viral titers were calculated and expressed as the tissue culture infectious dose (TCID50) per mL. The luciferase assay was performed according to a previously described protocol18. The luciferase activity of the culture supernatants was measured using a Nano-Glo HiBiT lytic detection system (Promega, Madison, WI, USA) according to the manufacturers protocol. Twenty L of culture medium was mixed with an equal volume of Nano-Glo HiBiT lytic buffer. Luciferase activity was measured in a 96-well LumiNunc plate (Thermo Fisher Scientific) using the microtiter plate reader POWERSCAN 4 (DS Pharma Biomedical, Osaka, Japan). The average number of mock-infected 96-well plates plus five times the standard deviation of this population (i.e., luciferase activity=70) was set as the cutoff value.

The pRF vector containing an FMDV-IRES (serotype C; 5-UTR sequence: nucleotides (nt) 5691038 in FMDV serotype C, AF274010.1)19 was kindly donated by Dr. Hirasawa of the Memorial University of Newfoundland, and those containing a CSFV-IRES20 were gifts from Professor Graham J. Belsham of the University of Copenhagen. The pCAGGS-Neo vector was constructed using the pCAG Neo (Fujifilm Wako, Tokyo, Japan) and pCAGGS vectors (Cat. No. RDB08938; Riken Bank, Ibaraki, Japan). The CSFV-IRES cDNA (nt. 124401) was excised from a reporter plasmid20 using the EcoRI and NcoI restriction sites, and the excised DNA was inserted between the Renilla and firefly luciferase genes. Reporter genes were cut using the restriction endonucleases EcoRV (Toyobo, Osaka, Japan) and BamHI (New England Biolabs, Ipswich, MA, USA). A pCAGGS-Neo/CSFV-IRES vector was generated by inserting a reporter gene into pCAGGS-Neo, which was subsequently treated with EcoRV (Toyobo), BamHI (New England Biolabs), and rAPid alkaline phosphatase (Roche, Basel, Switzerland) using a ligation mixture (Mighty Mix, Takara, Shiga, Japan).

Cells expressing pCAGGS-Neo-CSFV-IRES (clones pCI5 and pCI5-1) and pCAGGS-Neo-FMDV-IRES (clones B5 and B10) were established as described previously15.

DNA sequencing was performed by FASMAC Co. (Kanagawa, Japan), and DNA sequence characterization was performed using the GENETYX-Mac software (GENETYX Co., Tokyo, Japan) and GENBANK.

Cell viability was evaluated using WST assays (Dojindo, Kumamoto, Japan) by determining the optical density at 450nm (OD450) according to the manufacturers instructions. Luciferase assays were performed using a dual-luciferase reporter assay system (Promega, Madison, WI, USA). Luminescence was measured using a GloMax 96 Microplate Luminometer (Promega) for 10s, as described previously14.

Total RNA was extracted from PYC-treated (10g/mL, 72h) and untreated B10 cells using ISOGEN (Nippon Gene Co. Tokyo, Japan) from cells growing in the linear phase of PYC treatment. RNA quality was measured using an Agilent 2100 bioanalyzer and showed an RNA integrity number (RIN) of 9.8 (7.0

The amounts of PKD1L3 and USP31 mRNA in cells were quantified using the SYBR Green real-time PCR master mix (Thermo Fisher, Waltham, MA, USA) and the primers pKD1L3-544S: 5-CATCTTCCAACCACATGTCACTATCC-3, pKD1L3-903AS: 5-CTGTAGTTTGTTAAGAGCTTGCAAACC-3; USP31-700S: 5- TGTGGCTTTTGGACCGAGTTGC-3, and USP31-900AS: 5- TGCAGTGAGAACATTTGCCTGC-3. The data was evaluated using the 2Ct method.

The siRNAs targeting host factors (summarized in Table 2) were designed using the BLOCK-iT RNAi Designer (Thermo Fisher Scientific, Waltham, MA, USA). For the control siRNA, an ON-target plus siRNA control (Horizon/Dharmacon, Lafayette, CO, USA) was used. Then, siRNA (5nM) reverse transfection was performed using the Lipofectamine RNAiMAX reagent (Invitrogen) according to the manufacturers specifications. The effect of siRNA was evaluated by immunoblot analysis as described previously14 using anti-polycystic kidney disease 1-like 3 (PKD1L3) (OSP00014W, Invitrogen) and anti-ubiquitin-specific peptidase 31 (USP31) (Santa Cruz Biotechnology Co.) antibodies. Original blots presented in the supplementary original gel image_Fig. 5 which shows fuller-length of both sides and bottom, but top stacking part gel was removed.

All data are presented as meanstandard deviation (S.D.) from three independent experiments, and figures were generated using GraphPad Prism (version 9) software. Statistical analysis was performed using Students t-test to evaluate significant differences. Statistical significance was set at P<0.05.

This study was performed in accordance with institutional committee protocols of Kagoshima University.

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Characterization of host factors associated with the internal ribosomal entry sites of foot-and-mouth disease and classical swine fever viruses |...

The research, which appears in the journal Science Advances, lays the groundwork for developing future cancer treatments for humans.

An estimated 13% of diagnosed lung cancer is SCLC. According to the National Organization for Rare Disorders, SCLC is an aggressive type of cancer characterized by rapid, uncontrolled growth of certain cells in the lungs.

If SCLC is caught early and before it has spread, treatments can control the disease in up to 25% of cases.

The authors of the recent study wanted to understand the role of EP300 gene mutations in SCLC.

Medical News Today spoke with the corresponding authors of the study:

The current prognosis for SCLC patients is particularly poor with only 7% of patients surviving beyond 5 years. This reflects a lack of well-validated targets for therapy and a concomitant lack of targeted agents to treat the disease, they explained.

It is critical to garner further insights as to the drivers of the disease as well as develop drugs targeting those drivers. However, relevant pre-clinical models of SCLC carrying recurrent driver mutations were scarce, precluding the study to assess the physiological role of the mutations and the therapeutic impact of restoring their normal functions. So we built pre-clinical models using genetically engineered mice and cells.

By studying genetically engineered mouse models, the researchers found that EP300 the protein that the EP300 gene codes for can either promote or inhibit SCLC.

Specifically, they found that part of the EP300 protein known as the KIX domain was essential for the development of SCLC.

EP300 is a multi-functional protein and loss of its histone acetyltransferase domain function as predicted based on the mutations observed in SCLC patient tumors drives the cancer. This idea was validated by the findings from the pre-clinical models, they explained.

Unexpectedly, however, the models also showed that the KIX domain of the mutant EP300, which remains intact, drives the disease. Specifically, the protein-protein interactions mediated by the KIX domain of EP300 are critical for the survival of SCLC cells and vulnerable to inhibition. This was shown both in a mouse model as well as using human SCLC cell lines.

This validates the KIX domain of EP300 as a target for drug development for the treatment of SCLC, specifically a protein-protein interaction inhibitor of the KIX domain, said Drs. Park and Bushweller.

The finding may also have relevance for other types of cancer. According to the corresponding authors, EP300 mutations are widespread and have been implicated as having a critical role in other cancers including leukemia and triple-negative breast cancer.

MNT spoke with Dr. Charles Evans, research information manager at Cancer Research UK, who was not involved in the study.

This work highlights a key vulnerability that could be a target for potential new treatments, not only for small-cell lung cancer but also for other cancer types.

Dr. Evans

Right now, we only have a limited range of chemotherapy treatments available for people with small-cell lung cancer many of which can have harsh side effects, said Dr. Evans.

This study highlights a potential vulnerability for small-cell lung cancers, which could be exploited with new, targeted drugs in the future. However, more studies will be needed to confirm these results and develop a new treatment approach.

Dr. Evans said that the findings were one of a number of potential new treatment options for cancer.

There are other promising areas of research that are happening right now, such as the development of immunotherapies that can harness the power and precision of our immune systems to tackle cancer.

And innovations in radiotherapy, including new techniques such as proton beam therapy, have the potential to target tumors with a stronger dose far more precisely, limiting damage to surrounding tissue and reducing the burden of long-term side effects from treatment.

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Gene found to block small-cell lung cancer proliferation in mice - Medical News Today

(The Conversation is an independent and nonprofit source of news, analysis and commentary from academic experts.)

Steven Walkley, Albert Einstein College of Medicine and Melissa Wasserstein, Albert Einstein College of Medicine

(THE CONVERSATION) Mr. and Mrs. Smith, we finally have an answer for you. The couple, whose real names we are protecting for privacy, looked at me anxiously. I had been evaluating their young daughter, Sally, in my role as a medical geneticist at the Childrens Hospital at Montefiore in the Bronx, a borough of New York City. For years, the Smiths had been searching to learn why Sally was suffering from epilepsy, why she didnt seem to understand them and why she wasnt speaking at 6 years of age. In 2021, they ended up in my clinic.

I decided to send a sample of Sallys blood for whole-exome sequencing, a test that could identify a change in one of her genes that might be responsible for her symptoms. A few weeks later I had the answer.

Sally has an extremely rare disorder that youve probably never heard of, I told them. Its so rare that it doesnt even have a real name yet. Its called NAA10-related disorder. The family looked at me with blank stares. I took a deep breath and continued.

The NAA10 gene codes for an enzyme that modifies critical proteins, enabling them to function properly. A single change in Sallys NAA10 gene would cause the enzyme to be made incorrectly, resulting in intellectual disability and seizures. The NAA10 gene is located on the X chromosome, which is one of two sex chromosomes in humans.

Males typically carry an X and a Y chromosome, while females usually have two X chromosomes; as a result, boys are usually more severely affected and girls have a less predictable course. I explained to the family that only about 50 other people with NAA10-related disorder have been reported across the globe. They then asked me about treatment. I replied sadly, none. I could see them struggling to wrap their heads around this.

They asked further questions about what might happen to Sally: Will she learn to speak? Will she be able to learn? Will she grow old? I told them that there is not enough experience to accurately predict what Sallys future will look like. Feeling useless, I said, Here is a patient support group that might be helpful. And with nothing more to offer, I added: Ill see you in a year.

Moments like this a long-awaited answer that is met with more bewilderment than relief are not uncommon in the practice of medical genetics. Most people expect that after a long, frustrating search, finding the underlying diagnosis will provide answers and a path forward. But sometimes, in cases like Sallys, the answer simply begets more questions.

Weve faced these difficult questions as two researchers with decades of experience in rare genetic diseases. One of us is a medical geneticist whose clinical work focuses on the diagnosis and management of individuals with rare genetic disorders; the other is a neuroscientist working to determine how rare genetic diseases impact brain function and possible ways to correct them.

Putting rare disease into context

Most so-called rare diseases are poorly understood and have no treatment. The National Institutes of Health has estimated that there are about 7,000 rare diseases, defined as ones affecting fewer than 200,000 Americans. Many rare diseases, however, are like NAA10-related disorders and affect only a handful of individuals.

Major advances in the precision and speed of gene sequencing technology followed by dramatic reductions in the costs of testing have radically changed how medical genetics clinics function. Next-generation genetic sequencing, which was so expensive just a decade ago that it was used only after all other testing options had been exhausted, is now the go-to test in most clinics.

But while sequencing can provide confirmation of a suspected, well-understood condition, it frequently results in a situation like that faced by the Smiths, where the testing result shows an incredibly rare disorder with little known about it.

Putting the puzzle pieces together

The speed and ease with which modern gene sequencing can generate a diagnosis stand in sharp contrast to the prolonged effort required to understand how the genetic variant causes disease. Humans all have the same 20,000-plus genes, which govern the traits that make us characteristically human, such as a large brain, 10 fingers and round pupils. Changes, or variants, in these genes determine our uniqueness. So while we all have genes that tell our bodies to make hair, variants in these genes can make hair that is straight or curly, brown or red. Some genetic variants, however, change the gene product so significantly that they result in disease.

Unraveling the natural history of a rare condition requires years of focused attention by clinicians and scientists. Researchers like us also work to piece together the complex puzzle of how a rare genetic difference can alter metabolic pathways in the brain, as well as other organs that might be affected.

Over time, a fuller picture of the rare disorder begins to emerge. The role of the gene in normal cells or commoner diseases unfolds, as well as possible therapies. For instance, potential treatments might involve replacing or modifying a gene that isnt properly functioning, infusing a vital enzyme that an individuals body isnt making or prescribing a specialized diet or medications. But before one can determine how to treat a genetic disease, researchers first need to determine what is altered and not working normally. Only after this is understood can we begin to envision treatment.

Personalized medicine offers a way forward

To provide our patients and their families with more answers, we here at the Albert Einstein College of Medicine have begun a program in which we build what we call Gene Teams. These consist of parents or caregivers, their childs physician and interested scientists and their trainees. These researchers are typically working on deciphering the genes function, its encoded protein or the role the gene or protein plays inside of cells.

We bring all the team members together, and the childs physician outlines what is known about the clinical condition, followed by the parents sharing their childs story. The scientists and their trainees then provide an accessible tutorial to the families about what the gene and its associated protein do in cells. Whenever possible our team also discusses ways by which the condition could be treated.

These tutorials are the first encounters in ongoing relationships. Remarkably, three different families who were empowered by their Gene Team experience have gone on to establish foundations focused on their childs disease, and they have built networks to other families affected by the same rare condition worldwide. These are the STAR Foundation for SLC17A5, the KARES Foundation for KDM5C and the CACNA1A Foundation. The scientists, too, after the team meetings, have often gone on to build major research projects, some focused on the exact variant observed in the affected child.

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We as scientists and our trainees have also been transformed by our involvement with the Gene Teams. Working directly with the families brings real-life experience to our laboratory work and inspires us and other researchers to remember that our work matters not only for expanding scientific knowledge but also for helping families in need.

We have learned that the blank stare experienced in the doctors office following diagnosis of a rare disease can be transformed by empowering families not only with greater knowledge of the involved gene, but also with an understanding that they are not alone and that there can be a more hopeful path forward.

This article is republished from The Conversation under a Creative Commons license. Read the original article here: https://theconversation.com/when-it-comes-to-the-rarest-of-diseases-the-diagnosis-isnt-the-answer-its-just-the-starting-point-177424.

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When it comes to the rarest of diseases, the diagnosis isn't the answer it's just the starting point - Jacksonville Journal-Courier

The major pharma and biotech money winners this week were tech-heavy, including a DNA editing platform, a machine-learning platform that creates digital patient twins and wearable temperature-monitoring patches. Continue reading for that and more.

Tessera Therapeutics

Genetic medicine pioneer Tessera Therapeutics raked in a huge Series C financing worth more than $300 million. The funding was led by Flagship Pioneering, a subsidiary of the Abu Dhabi Investment Authority, Alaska Permanent Fund Corporation and Altitude Life Science Ventures, among others.

The Series C attracted many investors because of Tesseras unique genetic gene writing technology. Unlike CRISPR gene editing, which destroys damaged DNA, Tesseras gene writing platform writes new sequences of DNA into the genome. This gives the unique platform the potential to both cure and prevent nearly any disease at a scalable level.

We are thankful for the support from our new partners and existing investors alike in this latest funding round. It is our belief that genetic medicine will be the most important next epoch in medicine, said Geoffrey von Maltzahn, Ph.D., CEO of Tessera Therapeutics.

Unlearn.AI

Unlearn is a machine-learning technology that creates a digital twin of patients in clinical trials to enable smaller, faster studies. The unique company closed a $50 million Series B round this week, led by Radical Ventures, Insight Partners, DCVC Bio and Mubadala Capital Ventures.

The funding will help advance Unlearns TwinRCT platform feature, which uses a patients medical history, disease information and AI to essentially create an extra patient that functions as though it were receiving a placebo treatment in a trial. This allows the real patients to receive the trial medication and potentially benefit from it. The funding will also help expand Unlearns goal of expanding into clinical trials.

Blue Spark Technologies

As a leader in wearable remote patient monitoring solutions, Blue Spark Technologieswas able to raise a $40 million growth fund. The funding is an intellectual property-based debt solution led by Ghost Tree Partners and Aon. With the monetary support, Blue Spark hopes to create more patient monitoring solutions. Currently, its only product on the market is TempTraq, a Bluetooth-enabled disposable patch that patients wear to monitor fever spikes for up to 72 hours. TempTraq is an FDA-cleared Class II medical device, and Blue Spark says it has more products in the pipeline.

Having Ghost Trees support and expertise will be invaluable as we continue to expand our remote patient monitoring solutions to the market, said John Gannon, president and CEO of Blue Spark.

Alzheon

Massachusetts-based Alzheon, a clinical-stage biopharma company developing therapies to treat and diagnose Alzheimers disease, closed an oversubscribed Series D round of financing worth $50 million. The press release said that the funding came from private and institutional investors, but did not name anyone specifically.

The funding will largely go toward Alzheons ALZ-801 drug, an oral agent that blocks the formation of amyloid plaque in the brain, a significant contributor to Alzheimers Disease. ALZ-801 has shown positive results throughout a Phase II biomarker trial, and Alzheon hopes the Series D financing will help bring the product to market.

Trevena

Trevena, a biopharma company that develops medicines to treat Central Nervous System (CNS) diseases, received a $15 million tranche from its royalty-based financing agreement with an affiliate of R-Bridge Healthcare Fund. The original agreement totaled roughly $40 million and included an initial $15 million tranche, $15 million for the sale of opioid-based analgesic Olinvyk to China, and $10 million dependent on achieving milestones.

R-Bridge is an affiliate of CBC Group, one of Asias largest pharma and biotech groups. R-Bridge will receive royalties from Trevenas license with Jiangsu Nhwa Pharmaceutical and is hoping to have Olinvyk approved by China by the end of 2023.

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Money on the Move: Tessera, Unlearn.AI, Blue Spark, Alzheon and Trevana - BioSpace

By Ed Miseta, Chief Editor, Clinical LeaderFollow Me On Twitter @EdClinical

Recent years have seen unprecedented innovation in the clinical space. Precision medicine, cell and gene therapies, decentralized trials, real-world data, and the promise of artificial intelligence (AI) and machine learning (ML) are just a few of the reasons to be excited about the future of clinical research. But what can we expect to see in the next three years, and what are the challenges sponsor companies will need to overcome?

A webinar hosted by IBM Watson hoped to answer those questions. The discussion featured Lorraine Marchand, general manager of life sciences at IBM Watson Health; Nimita Limaye, research VP, Life Sciences R&D Strategy and Technology at IDC Health Insights; and Greg Cunningham, director of the RWE Center of Excellence at Eli Lilly and Company. The three shared insights into what we might expect to impact trials over the next three years.

In this article the panel discusses precision medicine and real-world data. In part 2 of this article the panel looks at the future of decentralized clinical trials.

The Growth Of Precision Medicine

The first game changer the panel discussed is the advancement of precision medicine. It has moved from exploring single gene mutations to performing research using combinations of genes. This change has the potential to bring better drug targets forward and get the best products to patients faster.

This has been playing out in the last decade in oncology real-world evidence, notes Cunningham. We've seen an evolution in precision medicine as we've built out the patient record. As we have done that, the marketplace has evolved rapidly, particularly for electronic medical record data and genomic data.

Pharma companies were happy to get their hands on electronic medical record data. When genetic test results were combined with that data, researchers gained the ability to look at a single mutation and develop better patient outcomes.

Where precision medicine will continue to evolve in 2022 and beyond is the growing use of genetic testing in oncology. This will provide the industry with more data about patients. With more genes at their disposal, researchers can look at groups of genes and the complex combinations of gene mutations. This has the potential to open the door for tools like artificial intelligence to help researchers analyze the complex number of permutations.

RWD Creates More Efficient Research

Next the panel discussed RWD and the ability to utilize it across several use cases from discovery and development to commercial. Limaye likes the prospect of being able to create a data exchange where researchers can bring together claims, clinical, EMR, and genomics data directly from patients to create an intelligent and digital patient health record. That record gives researchers the digital equivalent of a real-life patient which can be used as a natural history or synthetic control arm in randomized control clinical trials.

These data can allow drug developers to track patient response to drugs and look at outcomes after being exposed to new therapies. The promise of data and technology is using tools like AI to advance therapies and get them to patients faster. This will be done with better information and a much more efficient way to perform drug development and track and monitor outcomes in patients.

Big data has been a topic of discussion in pharma for years. The volume of clinical data is now growing exponentially. Approximately 30% of the world's datavolume is being generated by the healthcare industry and by 2025, the compound annual growth rate will hit 36%. That's 6% faster than manufacturing, 10% faster than financial services, and 11% faster than media & entertainment.

In addition to getting bigger, data is also getting broader. Researchers can not only look at a patients medical history but can now consider factors such as social determinants of health and behavioral data.

Since most EHRs do not include genomic data, researchers need the ability to look at patient data more holistically. Type 2 diabetes was one example discussed. Today, 40% to 70% of it is genetically inherited and there are over 500 different genetic loci which could be involved in causing the disease. The earlier strategy of looking at genetic risk scoring was single trait. That is now transitioning to multi-trait research with an integrated view that will drive a precision medicine strategy. This creates an interesting situation where drug discovery will continue to get more specific and focused towards an individual while also getting bigger and broader.

The Challenge Of RWD

With access to RWD, drug developers can benefit from data they may not have known existed. Although the data is rich and robust, it can be difficult to access. One of the biggest challenges the industry faces is data stored in silos. The panel notes data is stored in patient claims, electronic medical records, in lab apps, images, and genetic files on a smartphone. Having the technology to tap into those sources to identify quality data is the primary challenge.

The data must be de-identified for patient privacy, cleaned, curated to remove noise, and enriched, which means bringing together the various components that will be meaningful to drug development. That will allow researchers to have a patient record that is useful across pharma, from development through to commercial. An exchange would enable that exact process a platform where various entities can bring their data to have it linked, integrated, cleaned, and enriched, creating a data package that can be plugged into studies.

An important component of that exchange is the data being housed in a place where various third parties can feel comfortable bringing their data to match it with data from other third parties.

Cunningham cites lupus as an example of where pharma could benefit from such an exchange. I would like to have a complete data set of lupus, he says. Lupus is an autoimmune condition, and a quintessential data set could be used for a number of uses, such as preparing a Phase 1 trial, selecting patients, or understanding patient responses to different therapies when designing studies. Specific data sets could be created for each therapeutic area, and pharma companies need that hard work of bringing the data together removed.

Data Assembly And Analysis

Currently, drug developers spend 80% of their time assembling data and 20% of their time analyzing it. The situation must be flipped so that 80% of the time is spent performing analysis. The panel recommends rethinking how health records are created. The healthcare and life science industries require the ability to easily put data together. That comes back to investing in data standards everyone can agree upon. With the right standards and technology, the industry can spend its time improving lives as opposed to assembling data.

The FDA has indicated it is aware and supportive of the fact that pharma needs use RWD in drug discovery. The industry now needs to create the interoperability, standards, and methods to ensure that data can be included in regulatory submissions. This evolution may be akin to the critical path initiative. When the FDA embraced the idea of the critical path and allowing more in silico modeling of clinical trial design and development, it took the industry almost 10 years to adopt and apply the guidance.

The FDA has said it recognizes the importance of RWD, but that acknowledgement has resulted in few approvals. Looking at the use of synthetic control arms and RWD in regulatory submissions over the last five years shows just 10 submissions and all were in oncology. Only one was a successful submission, and the rest were rejected because of lack of completeness of the data.

Those numbers should tell the industry the FDA is not going to dictate how to get to approvals. The industry is going to have to figure out the interoperability and how to apply the standards. Regulators are always going to require quality data. Industry will need to enrich the data and create the cohort that is going to be equivalent to a patient in the real world.

In part 2 of this article, the panel discusses the role of technology in clinical trials, how decentralized trials will continue to evolve, what capabilities sponsor companies will need, and whether decentralized trials might offer cost benefits to companies.

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The Next Three Years Of Clinical Trials DCTs RWE And Beyond - Clinical Leader

Bordeaux, France / April 19th, 2022 TreeFrog Therapeutics, a biotechnology company aimed at making safer, more efficient and more affordable cell therapies based on induced pluripotent stem cells (iPSCs), today announced the launch of The Stem Cell SpaceShot Grant, a $100,000 research funding in the field of stem cell biology and regenerative medicine.

The Stem Cell Spaceshot Grant is open to PhD-level scientists and PhD students conducting research in stem cell biology, biophysics, gene editing, cell therapy, and bioproduction engineering. With this grant, TreeFrog Therapeutics aims at supporting scientific discoveries with therapeutic impact in 4 areas:

1. Progressing stem cell culture and cell therapy products through biomimetic strategies

2. Upgrading stem cell-products and manufacturing processes using new technologies and scientific approaches

3. Improving the quality control and safety profile of stem cells and stem cell-derived transplants

4. Enhancing the engraftment, integration and long-term survival of stem-cell derived transplants

To apply, researchers only need to submit an email, a one-page research project description and a graphical abstract through an online form available on the TreeFrog Therapeutics website. Applications will be opened from May 1st to June 30th 2022. 10 nominees will be selected in August 2022. The winner will be awarded in October 2022 following interviews with an interdisciplinary jury composed of world-class experts in stem cell biology, gene editing and biophysics:

Emeritus Prof. Peter ANDREWS, University of Sheffield, UK STEM CELL GENOMIC INTEGRITY

Prof. L. MAHADEVAN, Harvard University, USA BIOPHYSICS

Marta SHAHBAZI, PhD, MRC Laboratory of Molecular Biology, Cambridge, UK DEVELOPMENTAL BIOLOGY

Justin EYQUEM, PhD, University of California San Francisco, USA GENE EDITING

Shin KAWAMATA, MD, PhD, R&D Center for Cell Therapy, FBRI, Kobe, Japan CELL THERAPY MANUFACTURING & QUALITY CONTROL

Pierre NASSOY, PhD, CNRS, France BIOIMAGING & OPTOFLUIDICS

The technology of TreeFrog Therapeutics emerged at the cross-roads of stem cell biology and biophysics after I met my co-founder, Kevin Alessandri, in an atomic bunker of the Geneva University while we were post-docs. Today, our C-StemTM technology demonstrated its capacity to mass-produce stem cells and stem cell-derived products with unprecedented scalability and quality, and TreeFrog Therapeutics raised over $82M to advance a pipeline of cell therapies to the clinic and finance the global deployment of C-StemTM. I believe its now our role to encourage the next generation of scientists to make discoveries that will shape the future of regenerative medicine. We designed the grant that we would have liked to apply to: the application process is simple, fast and anonymous - so that it is ideas, rather that resumes that are awarded , no cumbersome reporting is required, and the intellectual property of scientists is preserved. I cant wait to read the first projects!

Maxime Feyeux, PhD, co-founder and Chief Scientific Officer, TreeFrog Therapeutics

About TreeFrog Therapeutics

TreeFrog Therapeutics is a French-based biotech company aiming to unlock access to cell therapies for millions of patients. TreeFrog Therapeutics is developing a pipeline of therapeutic candidates using proprietary C-StemTM technology, allowing for the mass production of induced pluripotent stem cells and their differentiation into ready-to-transplant microtissues with unprecedented scalability and cell quality. Bringing together over 70 biophysicists, cell biologists and bioproduction engineers, TreeFrog Therapeutics raised $82M over the past 3 years to advance its pipeline of stem cell-based therapies in the field of neurodegeneration, cardio-metabolic disorders, and immuno-oncology. In 2022, the company will open technological hubs in Boston, USA, and Kobe, Japan, to drive the adoption of C- StemTM and initiate co-development partnerships with leading academic, biotech and industry players in the field of cell therapy.

Media Contact

Pierre-Emmanuel Gaultier

TreeFrog Therapeutics

+ 33 6 45 77 42 58

pierre@treefrog.fr

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TREEFROG THERAPEUTICS LAUNCHES A $100,000 RESEARCH GRANT IN REGENERATIVE MEDICINE - BioSpace

Posoleucels third RMAT designation marks an unprecedented regulatory distinction among cell and gene therapies

Global Phase 3 multi-virus prevention trial initiated in March 2022 and is enrolling patients

WALTHAM, Mass., April 20, 2022--(BUSINESS WIRE)--AlloVir (Nasdaq: ALVR), a late clinical-stage allogeneic T cell immunotherapy company, today announced that the U.S. Food and Drug Administration (FDA) has granted Regenerative Medicine Advanced Therapy (RMAT) designation to its lead investigational multi-virus-specific T cell therapy, posoleucel, for the prevention of clinically significant infections and disease from six devastating viruses that commonly impact high-risk adult and pediatric patients following allogeneic hematopoietic cell transplant (allo-HCT) adenovirus (AdV), BK virus (BKV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpes virus-6 (HHV-6) and JC virus (JCV). This is the third RMAT designation that FDA has granted to posoleucel, in recognition of the therapys transformative potential to address significant unmet medical needs facing immunocompromised allo-HCT patients.

The FDA previously granted RMAT designation to posoleucel for the treatment of hemorrhagic cystitis (HC) caused by BKV in adults and children following allo-HCT and for the treatment of adenovirus infection following allo-HCT. RMAT designation enables early interactions with the FDA to discuss clinical trial design and other actions to expedite development and review. Outside of the United States, the European Medicines Agency has granted posoleucel PRIority Medicines (PRIME) designation for the treatment of serious infections with AdV, BKV, CMV, EBV and HHV-6.

"The receipt of three RMAT designations for a single therapy is unprecedented. Posoleucels three RMAT designations reflect the strength of AlloVirs multi-virus platform and its potential both to deliver an important treatment option for immunocompromised patients who currently have none, and to transform the management of allo-HCT patients with a multi-virus prevention approach," said Ercem Atillasoy, M.D., Chief Regulatory and Safety Officer, AlloVir.

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Posoleucel has the potential to fundamentally transform the landscape for allo-HCT by preventing life-threatening viral diseases and infections, either as a prophylactic therapy in high-risk patients or as a preemptive therapy in patients who have already reactivated one or more of the six viruses targeted by posoleucel. As 90% of allo-HCT patients reactivate at least one of these viruses, there is a large global market opportunity for the prevention of devastating viral diseases, with an estimated addressable patient population of 40,000 allo-HCT patients annually.

The new RMAT designation was based on initial data from an open-label Phase 2 study evaluating the potential for posoleucel to prevent life-threatening infections from six common viruses following allo-HCT. Initial data from this study were most recently presented at the 48th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT) in March 2022. Out of 26 patients who received at least one dose of posoleucel in the ongoing Phase 2 trial, and including those who completed, discontinued or are continuing posoleucel, only three clinically significant infections were observed through Week 14, as of the data cut-off for this analysis. Of the 24 patients who had reached the Week 14 primary endpoint, 21 remained free of clinically significant infections. Repeat dosing was generally well-tolerated. Final results of the Phase 2 study are expected to be available at the end of this year.

About Posoleucel

AlloVirs lead product, posoleucel, is in late-stage clinical development as an allogeneic, off-the-shelf, multi-virus specific T cell therapy targeting six viral pathogens in immunocompromised individuals: adenovirus (AdV), BK virus (BKV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpes virus-6 (HHV-6) and JC virus (JCV). In the positive Phase 2, proof-of-concept CHARMS study, more than 90% of patients who failed conventional treatment and received posoleucel, demonstrated a complete or partial clinical response based on predefined criteria, most with complete elimination of detectable virus in the blood and resolution of major clinical symptoms.

Posoleucel is being studied in three Phase 3 clinical trials for three distinct indications - the treatment of virus-associated HC, the treatment of AdV infection, and the prevention of infections and disease caused by posoleucels six target viruses. A Phase 2 proof-of-concept trial with posoleucel for the preemptive treatment of BKV in adult kidney transplant recipients is also ongoing.

In addition to the RMAT designations for multi-virus prevention and for the treatment of AdV and virus-associated HC, the FDA has also granted posoleucel Orphan Drug Designation for the treatment of virus-associated HC. The European Medicines Agency has granted posoleucel PRIority Medicines (PRIME) designation for the treatment of serious infections with AdV, BKV, CMV, EBV and HHV-6, and Orphan Medicinal Product designation as a potential treatment of viral diseases and infections in patients undergoing HCT.

About AlloVir

AlloVir is a leading late clinical-stage cell therapy company with a focus on restoring natural immunity against life-threatening viral diseases in pediatric and adult patients with weakened immune systems. The companys innovative and proprietary technology platforms leverage off-the-shelf, allogeneic, single- and multi-virus-specific T cells for patients with T cell deficiencies who are at risk from the life-threatening consequences of viral diseases. AlloVirs technology and manufacturing process enable the potential for the treatment and prevention of a spectrum of devastating viruses with each single allogeneic cell therapy. The company is advancing multiple mid- and late-stage clinical trials across its product portfolio. For more information, visit http://www.allovir.com or follow us on Twitter or LinkedIn.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding AlloVirs development and regulatory status of our product candidates, the planned conduct of its preclinical studies, and clinical trials and its prospects for success in those studies and trials, and its strategy, business plans and focus. The words "may," "will," "could," "would," "should," "expect," "plan," "anticipate," "intend," "believe," "estimate," "predict," "project," "potential," "continue," "target" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on managements current expectations and beliefs and are subject to a number of risks, uncertainties, and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, those related to AlloVirs financial results, the timing for the initiation and successful completion of AlloVirs clinical trials of its product candidates, whether and when, if at all, AlloVirs product candidates will receive approval from the U.S. Food and Drug Administration, or FDA, or other foreign regulatory authorities, competition from other biopharmaceutical companies, the impact of the COVID-19 pandemic on AlloVirs product development plans, supply chain, and business operations and other risks identified in AlloVirs SEC filings. AlloVir cautions you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. AlloVir disclaims any obligation to publicly update or revise any such statements to reflect any change in expectations or in events, conditions, or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements. Any forward-looking statements contained in this press release represent AlloVirs views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date.

View source version on businesswire.com: https://www.businesswire.com/news/home/20220420005069/en/

Contacts

Media and Investor Contact: Sonia ChoiAlloVirschoi@allovir.com

Excerpt from:
FDA Grants Regenerative Medicine Advanced Therapy (RMAT) Designation to AlloVirs Posoleucel for Prevention of Multiple Life-Threatening Infections...