Category Archives: Transhuman News

The next frontier in genetic medicines could be one-time therapies that do their editing work in vivo, inside the patient. But one challenge is that some genetic diseases have hundreds of mutations. To address all of them, youd need to produce a therapy for each mutationan endeavor thats just not scalable, according to Joseph Truitt, CEO of iECURE.

The number of mutations does not matter to iECURE. Whereas some of the in vivo gene editing therapies in development aim to fix specific mutations on a gene, iECURE aims to swap out the entire problem gene, making the approach independent of any one disease-causing mutation.

This is about gene insertion and replacement, replace a deficient gene with a healthy gene, Truitt said.

The Philadelphia-based company, which is based on the research of University of Pennsylvania scientist James Wilson, a gene therapy pioneer, has demonstrated that its approach can work in animals. Now iECURE has $50 million in Series A financing as it works to bring in vivo gene-editing therapies into human testing. The Series A round of funding announced Thursday was led by Versant Ventures and OrbiMed Advisors.

IECURE will use gene editing and in vivo approaches from Wilson, and the startup may choose up to 13 programs from his lab. Truitt said that iECURE has identified three diseases so far: familial hypercholesterolemia, phenylketonuria, and ornithine transcarbamylase deficiency. Theyre all rare liver disorders, which is the focus of the company.

Truitt said Wilson tried various kinds of gene-editing tools, including CRISPR, with little success, until landing on technology from Precision Biosciences. The clinical-stage biotech in Durham, North Carolina, has developed technology called ARCUS, which delivers a cutting enzyme called an endonuclease to a targeted segment of DNA. The endonuclease is delivered by adeno-associated virus (AAV), an engineered virus that is widely used in genetic medicines.

The Precision Bio enzyme, which is derived from algae, is the smallest compared to others used in gene-editing research, said Chief Scientific Officer Derek Jantz, speaking during the companys virtual R&D event Thursday. That smaller size means that more enzymes can fit onto an AAV, giving it the capability to perform complex edits, such as gene insertion, and do that work in multiple types of tissue.

Penn began working with Precision Bio in 2018, a partnership focused on developing in vivo gene-editing products using ARCUS. That year, preclinical research from the partnership was published in Nature Biotechnology showing that ARCUS was able to knock out the cholesterol-regulating gene PCSK9 in monkeys. In February of this year, Wilson published a paper in Molecular Therapy describing three-year data showing PCSK9 protein reductions of up to 85%, as well as a 56% reduction in LDL cholesterol levels. Also notable was that the one-time treatment continued to demonstrate safety with no adverse effects reported.

The Penn/Precision Bio research showed that ARCUS could knock out a gene thats causing disease. This collaboration paved the way for a new one that is proceeding with iECURE. The startup will also use ARCUS, but to knock in a healthy gene, or gene insertion. The startup has licensed from Precision Bio the rights to use ARCUS for four liver indications. In exchange, iECURE will advance Precision Bios PCSK9 therapy into Phase 1 testing for familial hypercholesterolemia.

Precision Bio gets an unspecified equity stake in iECURE and it also stands to earn milestone payments, plus royalties from sales, if any products that iECURE developed with ARCUS reach the market. But the North Carolina company stands to gain something more. Successful iECURE clinical trial results for therapies that use ARCUS would also provide validation for the technology in gene insertion, said Precision Bios top business development executive Cindy Atwell. The company is pursuing gene knockout validation through internal research, as well as through programs partnered with Eli Lilly.

Precision Bio and iECURE expect an application to begin clinical testing of the familial hypercholesterolemia candidate could be filed in early 2022. Concurrent with that program, iECURE will also work on the programs selected from Penn. The first two diseases the startup aims to address using ARCUS are phenylketonuria and ornithine transcarbamylase deficiency, Truitt said. The other two will be selected later. Precision Bio retains the rights to ARCUS for all other indications.

IECURE came together as a result of an informal meeting that Versant Managing Director Tom Woiwode had with Wilson two years ago, according to Truitt. Versant was one of the initial financial backers of Passage Bio, a now publicly traded gene therapy developer that Wilson had founded. Versants genetic medicine investments had also included gene editing companies, such as CRISPR Therapeutics and Graphite Bio. Wilson mentioned he had been quietly doing gene editing research for several years with a particular focus on neonatal disorders where gene therapies wont work.

One of Wilsons findings was that this gene insertion is best as a neonatal treatment. Newborns have rapidly dividing liver cells, which is necessary for the rapid uptake of the gene editing therapy, Truitt said. Adult livers do not have rapidly dividing cells and therefore, do not take up the therapies as well. Wilson had done research in familial hypercholesterolemia and ornithine transcarbamylase deficiency, and the animal data excited Woiwode, leading Versant to reach out to OrbiMed, another Passage Bio investor. They formed iECURE, bringing biotech industry veteran Truitt aboard as CEO in February. Wilsons lab came up with the name iECURE, a reference to iecur, the Latin word for liver. We added the e for cure, Truitt said.

Penn and Wilson hold equity stakes in iECURE; Wilson is not an employee of the company though he is an advisor, Truitt said. According to iECUREs agreement with the university, Wilsons lab will do the preclinical research and manufacturing of the programs selected by iECURE. When the research is ready for an investigational new drug application, iECURE will take over and handle clinical development, and if approved, commercialization.

Truitt said that the $50 million should support the company until early 2023. A big chunk of that cash will be for manufacturing. But Truitt notes that working with programs that have already been studied extensively by Wilsons lab puts iECURE well ahead of most startups raising their first rounds of funding.

Jim has three years of data with ARCUS, Truitt said. If we would have started all over again, we wouldnt have been able to use that. Its a brand new company but the programs are rather mature for a gene-editing company.

Photo: Mark Makela for The Washington Post, via Getty Images

Go here to read the rest:
Genetic meds pioneer James Wilson has a new startup, this time in gene editing - MedCity News

An Amgen sign is seen at the company's office in South San Francisco, California October 21, 2013. REUTERS/Robert Galbraith (UNITED STATES/File Photo

LONDON, Sept 10 (Reuters) - Lung cancer patients in England will become the first in Europe to receive a drug made by U.S. biotech Amgen Inc (AMGN.O) that targets a specific gene mutation, the country's health service said on Friday.

NHS England said it was fast-tracking lung cancer drug sotorasib after it was shown in clinical trials to stop lung cancer progression for seven months.

The drug, taken as a tablet, will be used on patients with the KRAS G12C mutation that occurs in about 13% of non-small cell lung cancers (NSCLC), the most common type of lung cancer.

The early-access deal will see 600 patients a year receive sotorasib in England through the state-run National Health Service (NHS).

"This revolutionary treatment has taken decades of research to reach the clinic, and now that it is here this new targeted drug will be available for eligible people with lung cancer as quickly as possible thanks to this agreement," said Peter Johnson, NHS clinical director for cancer.

Charles Swanton, chief clinician at charity Cancer Research UK, said the drug was "one of the most exciting breakthroughs in lung cancer treatment in 20 years, targeting a cancer gene that was previously untargetable."

The use of sotorasib in Britain follows its accelerated approval in May in the United States for lung cancer patients with the KRAS G12C mutation whose disease has worsened after treatment with chemotherapy or other medicines. read more It is sold in the United States under the brand name Lumakras.

Britain's medicine regulator, the Medicines and Healthcare products Regulatory Agency (MHRA), has authorised the drug under a partnership with U.S. and Australian counterparts designed to speed up approval for promising cancer treatments, called Orbis.

Reporting by Alistair SmoutEditing by Bill Berkrot

Our Standards: The Thomson Reuters Trust Principles.

Link:
Lung cancer patients in England to receive Amgen drug that targets a gene mutation - Reuters

Data to include patient safety assessments and a preliminary analysis of secondary endpoints to evaluate biological activity

Abstract selected for oral presentation on September 29

Company to host webcast investor event following the presentation on September 29 at 11:00 a.m. ET

CAMBRIDGE,Mass., Sept. 07, 2021 (GLOBE NEWSWIRE) -- Editas Medicine, Inc. (Nasdaq: EDIT), a leading genome editing company, today announced that an abstract featuring initial clinical data from the BRILLIANCE clinical trial of EDIT-101 has been selected for an oral presentation at the XIXth International Symposium on Retinal Degeneration (RD2021) being held in Nashville, Tenn., and virtually September 28 October 2, 2021. EDIT-101 is under development for the treatment of Leber congenital amaurosis 10 (LCA10), a CEP290-related retinal degenerative disorder.

We look forward to sharing our Companys first clinical data at RD2021 and our progress towards developing a transformative gene editing medicine for people living with CEP290-related retinal degeneration. The presentation will include an evaluation of clinical data from the first two adult cohorts as the study continues into the pediatric mid-dose and adult high-dose cohorts, said Lisa Michaels, M.D., Executive Vice President and Chief Medical Officer, Editas Medicine. I would like to thank all of the patients who have and will participate in this landmark gene editing medicine clinical trial.

The presentation will include patient safety assessments and a preliminary analysis of secondary endpoints relating to signals of gene editing and clinical benefit. Cumulative data from patients in the adult low-dose and mid-dose cohorts and will be presented by one of the studys Principal Investigators, Dr. Mark Pennesi, M.D., Ph.D., Professor of Molecular and Medical Genetics, Kenneth C. Swan Endowed Professor of Ophthalmology, Paul H. Casey Ophthalmic Genetics Division Chief, Casey Eye Institute, Oregon Health & Science University.

Story continues

Full details of the Editas Medicine presentations can be accessed on the RD2021 website at http://www.rdmeeting.net/RD2021Program.pdf.

Oral Presentation:Title: BRILLIANCE: A Phase 1/2 Single Ascending Dose Study of EDIT-101, an in vivo CRISPR Gene Editing Therapy, in CEP290-Related Retinal DegenerationSession Title: Platform Session V: Clinical TrialsDate and Time: Wednesday, September 29, 2021, 9:05 9:35 a.m. ETPresenter: Dr. Mark Pennesi, M.D., Ph.D., Professor of Molecular and Medical Genetics, Kenneth C. Swan Endowed Professor of Ophthalmology, Paul H. Casey Ophthalmic Genetics Division Chief, Casey Eye Institute, Oregon Health & Science University.

Investor Event and Webcast InformationEditas Medicine will host a live webcast on Wednesday, September 29, 2021, at 11:00 a.m. ET to review the presented data. To join the webcast, please visit this link or visit the Events & Presentations page of the Investor section of the Companys website on September 29. A replay of the webcast will be available on the Editas Medicine website for 30 days following the call.

About EDIT-101 EDIT-101 is a CRISPR-based experimental medicine under investigation for the treatment of Leber congenital amaurosis 10 (LCA10). EDIT-101 is administered via a subretinal injection to reach and deliver the gene editing machinery directly to photoreceptor cells.

About BRILLIANCEThe BRILLIANCE Phase 1/2 clinical trial of EDIT-101 for the treatment of Leber congenital amaurosis 10 (LCA10) is designed to assess the safety, tolerability, and efficacy of EDIT-101 in up to 18 patients with this disorder. Clinical trial sites are enrolling up to five cohorts testing up to three dose levels in this open label, multi-center study. Both adult and pediatric patients (3 17 years old) with a range of baseline visual acuity assessments are eligible for enrollment. Patients receive a single administration of EDIT-101 via subretinal injection in one eye. Additional details are available on http://www.clinicaltrials.gov (NCT#03872479).

About Leber Congenital AmaurosisLeber Congenital Amaurosis, or LCA, is a group of inherited retinal degenerative disorders caused by mutations in at least 18 different genes. It is the most common cause of inherited childhood blindness, with an incidence of two to three per 100,000 live births worldwide. Symptoms of LCA appear within the first years of life, resulting in significant vision loss and potentially blindness. The most common form of the disease, LCA10, is a monogenic disorder caused by mutations in the CEP290 gene and is the cause of disease in approximately 20-30 percent of all LCA patients.

About Editas MedicineAs a leading genome editing company, Editas Medicine is focused on translating the power and potential of the CRISPR/Cas9 and CRISPR/Cas12a (also known as Cpf1) genome editing systems into a robust pipeline of treatments for people living with serious diseases around the world. Editas Medicine aims to discover, develop, manufacture, and commercialize transformative, durable, precision genomic medicines for a broad class of diseases. For the latest information and scientific presentations, please visit http://www.editasmedicine.com.

Forward-Looking Statements This press release contains forward-looking statements and information within the meaning of The Private Securities Litigation Reform Act of 1995. The words anticipate, believe, continue, could, estimate, expect, intend, may, plan, potential, predict, project, target, should, would, and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. The Company may not actually achieve the plans, intentions, or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various factors, including: uncertainties inherent in the initiation and completion of pre-clinical studies and clinical trials and clinical development of the Companys product candidates; availability and timing of results from pre-clinical studies and clinical trials; whether interim results from a clinical trial will be predictive of the final results of the trial or the results of future trials; expectations for regulatory approvals to conduct trials or to market products and availability of funding sufficient for the Companys foreseeable and unforeseeable operating expenses and capital expenditure requirements. These and other risks are described in greater detail under the caption Risk Factors included in the Companys most recent Annual Report on Form 10-K, which is on file with the Securities and Exchange Commission, as updated by the Companys subsequent filings with the Securities and Exchange Commission, and in other filings that the Company may make with the Securities and Exchange Commission in the future. Any forward-looking statements contained in this press release represent the Companys views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Except as required by law, the Company explicitly disclaims any obligation to update any forward-looking statements.

Read more from the original source:
Initial Clinical Data from Editas Medicine's BRILLIANCE Clinical Trial of EDIT-101 for LCA10 to be Presented at the International Symposium on Retinal...

(UroToday.com)TheAmerican Urologic Association annual meeting included a State-of-the-Art Lecture by Dr. Brian Chapin who discussed personalized medicine in the management of prostate cancer across the patient care continuum. Dr. Chapin notes that the way we think about the personalized approach to prostate cancer therapy involves seeing a patient in the clinic and assessing them on a number of factors (clinical features, genetics, genomics, serum markers, receptors, induced responses, and selection pressures) and then developing a personalized approach to their treatment plan:

In setting the stage for personalized care, it is important to understand the available treatment options in the castration-nave setting, as well as the castration resistant setting:

Dr. Chapin notes that personalized care is compartmentalization by stage, histology and biology. Traditionally we have delineated care by stage of disease in combination with histologic considerations (ie. neuroendocrine, ductal, adenocarcinoma). More recently, there has become an increasingly more sophisticated approach, with regards to assessing the androgen receptor axis (TMPRSS2-ERG, SPOP, AR responsive), loss of tumor suppression (p53, PTEN, Rb), DDR mutations (BRCA, CDK12, FANCONI, CHEK1/2), and mismatch repair (MSI, Lynch syndrome).

Compartmentalization allows for better risk stratification, for example balancing arms in a clinical trial by using stratification factors (ie. M1a/b versus M1c) and balancing groups in retrospective studies by utilizing matching or propensity scoring (ie. NCDB, SEER database). However, this can also generate selection bias in retrospective cohort series, for example in patients with occult node positive prostate cancer, some patients will undergo a completion prostatectomy whereas others will have their radical prostatectomy aborted (thus, unable to compare outcomes). Many of us think of personalized care in prostate cancer by way of DNA, RNA, proteins and receptors, such as in the pre-biopsy, post-biopsy, positive biopsy, post-radical prostatectomy, and metastatic settings:

Dr. Chapin emphasizes that it is critically important to delineate between prognostic versus predictive biomarkers. Prognostic biomarkers are a variable associated with favorable or unfavorable outcomes for patients in the absence of treatment. Predictive biomarkers are a variable used to identify patients or groups of patients most likely to benefit from a specific therapy, for example a patient with a DNA damage repair mutation being a candidate for PARP inhibitor treatment, or a patient with a mismatch repair deficiency being a candidate for anti-PD1 antibody treatment. Prognostic variables can be used incorrectly thus mistakenly influencing management. For example, genomic tests on prostate biopsies have all been based on treated prostate cancer patients, thus these findings may not be applicable to an active surveillance cohort. Findings from these genetic tests are used to make changes in management decisions, resulting in Medicare approval. Dr. Chapin states that it is important to remember that no randomized trials have reported outcomes (although there are several ongoing) assessing if genomic tests improve patient outcomes, and in fact reflexive genomic testing may be detrimental to patients.

Dr. Chapin then discussed several potential predictive markers and prospective trials. The PAM50 gene expression classifier was previously described in the breast cancer literature, but has since been applied to prostatectomy specimens. Zhao et al.1 applied the classifier to 3,782 samples (1,567 retrospective, 2,215 prospective) noting that the PAM50 classifier consistently segregated prostate cancer into three subtypes in both retrospective and prospective cohorts:

Luminal A, luminal B, and basal curves separate based on PAM50 gene expression, with basal tumors having worse prostate-cancer specific survival:

When assessing luminal B and basal tumors with regards to response to ADT, this study suggests there may be a benefit to treatment of luminal B patients with ADT but no benefit seen in those with basal tumors:

Another example is the post-operative radiation therapy outcomes score (PORTOS), which is a genetic prediction score for post-op radiation. PORTOS is made up of 24 genes selected from a training set of 196 men and validate in a separate cohort of 330 men, with a clinical endpoint of metastasis over 10 years of follow-up.2 In this study, patients with a high PORTOS score had a benefit in cumulative incidence of distance metastasis with radiotherapy (HR 0.15, 95% CI 0.04-0.60), whereas patients with a low PORTOS score (HR 0.92, 95% CI 0.56-1.51) did not have a benefit with radiotherapy:

Biomarker examples have also been described in the advanced prostate cancer setting, specifically assessing androgen indifferent or aggressive variant prostate cancer. In a phase 1-2 trial assessing cabazitaxel plus carboplatin for men with mCRPC, at a median follow-up of 31.0 months, combination cabazitaxel plus carboplatin improved the median progression-free survival from 4.5 months (95% CI 3.5-5.7) to 7.3 months (95% CI 5.5-8.2; HR 0.69, 95% CI 0.50-0.95) with cabazitaxel alone.3 Dr. Chapin notes that what is particularly interesting is that for patients with a positive aggressive variant prostate cancer molecular signature, there was an improvement in overall survival with the addition of platinum based chemotherapy, whereas there was no benefit in those that were aggressive variant prostate cancer molecular signature negative. Dr. Chapin highlighted that there are several trials ongoing in the localized setting assessing a personalized approach, including the Genomic Umbrella Neoadjuvant Study (GUNS):

Decipher is a 22 gene classifier that provides risk stratification based on radical prostatectomy specimen analysis, which is prognostic for metastasis. However, there is no data on predictive ability, which is undergoing prospective evaluation in the NRG-GU009 PREDICT-RT trial:

Importantly, there are several barriers to overcome in the era of personalized medicine, including (i) assessing if findings are transferrable across stages of the disease; (ii) tumor heterogeneity, whether intertumoral, intratumoral, or comparing a metastases to the primary tumor; (iii) in order to move from prognostic to predictive markers, prospective trials are required; (iv) it is important to determine drivers in the setting of co-occurences (ie. DDR, +/- p53, +/- Rb1, +/- PTEN); and (v) assess selection pressures over time (ie. the predominant clone).

Dr. Chapin concluded his presentation with the following take-home messages from his presentation of personalizing medicine in the management of prostate cancer:

Presented by: Brian Chapin, MD, Associate Professor of Urology, MD Anderson Cancer Center, Houston, TX

Written by: Zachary Klaassen, MD, MSc Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2021 American Urological Association, (AUA) Annual Meeting, Fri, Sep 10, 2021 Mon, Sep 13, 2021.

References:

Read more from the original source:
AUA 2021: State-of-the-art Lecture: Personalized Medicine in the Management of Prostate Cancer Across the Patient Care Continuum - UroToday

Share this Article

You are free to share this article under the Attribution 4.0 International license.

Researchers have discovered a specific gene that drives much of the development of the stripes, blotches, and spots that decorate cat fur with patterns.

Color patterns are one of these unsolved biological mysteries; theres no go-to model organism to study itmice dont have stripes or spots, says Gregory Barsh, professor emeritus of genetics at Stanford University School of Medicine.

The color patterns and variability that you see in animals like tigers, cheetahs, and zebras prompted some central questions for us: What are the developmental genetic mechanisms and the cellular mechanisms that give rise to these patterns and how have they been altered during mammalian evolution to give rise to the amazing diversity of shape and form we see today?

Barsh and his team have answered part of that question: They have identified a gene, DKK4, that helps regulate the early development of the different fur patterns in domestic cats. DKK4, the team suspects, is likely involved in color patterns in all cats and perhaps other mammals, too.

The researchers findings appear in Nature Communications. Barsh is the senior author. Research scientists Christopher Kaelin and Kelly McGowan are co-lead authors.

The researchers previously identified a different gene that controls coat color variation in tabby cats. Its the same gene that accounts for the difference between cheetahs and king cheetahs, which have thicker, more prominent fur patterns.

We knew from studying domestic cats that there were other genes that contributed to color pattern formation; we just didnt know what they were, Barsh says.

They found a clue in fetal cat tissue that seemed to foreshadow fur color: a thickening of the skin tissue in certain areas. These thickened regions constitute a prepattern that mimics the eventual color patterns in an adult cats fur. The thick area marks the patches of fur that will later be darker; the thin area marks the patches that will be lighter.

We call this step establishment, and it happens long before color appears and long before hair follicles are mature, Barsh says.

The prepattern provided a map of sorts for the researchers, indicating cells involved in creating the pattern and the time when the pattern formed. The researchers then inspected the genetic makeup of individual cells in the thick and thin regions of skin. DKK4 was particularly active in the thickened skin, but not in skin that had remained relatively thin.

But to really lock in the connection between DKK4 and early pattern formation, the team turned to the Abyssinian cat. Abyssinians are known for sporting a blur of colors in their coat, with tiny, darker markings squished together, as if someone used a pencil to lightly shade a layer of gray on top of their orangish-brown coat. Barsh and his team identified disrupting mutations in the DKK4 gene responsible for the Abyssinian cats apparent lack of tabby markings, a look thats called ticked.

If you remove DKK4, the dark areas dont go away entirely, but they become smaller and more packed together, Barsh says.

You may be wondering, what about all-white cats? Or all-black cats? They, too, are patterned underneath their monochrome swath of fur. There are two distinct processes that make a color pattern: One that forms the pattern during embryonic development and one that translates the pattern into pigment produced in hair follicles. In solid-colored cats, the pattern is essentially overridden by instructions to produce dark pigment everywhere. In white cats, the pigment is lacking.

Scientists dont know exactly how DKK4 paints the array of color patterns domestic cats sport, but they do know DKK4 interacts with a class of proteins called WNTs, which are crucial in early development. WNTs and DKK4 help to form a prepattern when embryos are only two or three millimeters in length, weeks before pigment is produced in hairs. DKK4 is involved in marking areas that will eventually have darkly pigmented hairs, Barsh says, but how these skin areas remember their fate to induce target pigment is unclear.

This is one of the big unanswered questions in our workhow to connect the process of prepattern formation to the process that implements the pattern later in development, he says. Thats something that were actively trying to figure out.

On top of that, DKK4 is only part of the answer to the mysterious genetics dictating fur patterns. There are still other genes that are behind why, for instance, some cats have spots and why some cats have stripes, Barsh says. Looking into that is on their list, too.

Funding for the work came from the HudsonAlpha Institute for Biotechnology and the National Institutes of Health. Stanfords genetics department also supported the work.

Source: Stanford University

View original post here:
Gene helps put stripes and blotches on cats of all sizes - Futurity: Research News

iECURE is emerging from stealth with $50 million and a mission to go after the "holy grail" of gene editing with an in vivo approach that is mutation agnostic.

The biotech will use the funds for a slate of gene insertion programs for liver disorders out of the lab of gene therapy pioneerJim Wilson, M.D., Ph.D. at the University of Pennsylvania.

Versant Ventures, which has backed gene-editing companiesCRISPR Therapeutics and Graphite Bio,is launching iECURE alongside OrbiMed Advisors. The series A gives the biotech access to up to 13 programs out of Wilson's Gene Therapy Program at Penn.

Wilson's lab will conduct the preclinical, toxicology and manufacturing supportand then iECURE will sign the regulatory filings and move the assets through the clinic and onto the market, CEO JosephTruitt told Fierce Biotech.

Its a much more mature company than you would typically start off with if you were just licensing some technology from an academic center," Truitt said. By getting access to Wilson's team, iECURE doesn't have to recruit dozens of employees, the CEO said.

RELATED:FDA committee takes on complex gene therapy safety questions with Novartis' Zolgensma providing lessons learned

Wilson's lab has already shown long-term evidence of genome editing in non-human primates, which is important because translating into species larger than mice is often difficult, said Tom Woiwode, Ph.D., iECURE chairman and Versant managing director, in a joint interview with Truitt and Wilson.

Wilson has thought of the liver as a great target for gene therapy since the late-1980's, when he was in the lab as a post-doc, because "so many diseases have their root in the liver [and] it's accessible to biologics." Wilson is also director of the Orphan Disease Center and a professor in medicine and pediatrics at Penn's School of Medicine.

iECURE and Wilson's lab are approaching the "holy grail of genome editing" by using an in vivo approach that inserts genes inside organs, inside the human body, Woiwode said. In another adventurous analogy,Woiwode said the company is also going after the "untapped frontier of gene editing" by using a mutation agnostic approach. This is critical given many genetic diseases have multiple, "sometimes hundreds," of individual mutations. That many targets would not lend well to creating therapies at scale, the chairman added.

The series A will help iECURE bankroll the first three indications in the program of up to 13, Truitt said. More indications down the pipeline are still under evaluation. The financing is slated to take iECURE through the early part of 2023, the CEO said.

The first program goes after familial hypercholesterolemia, or high cholesterol caused by abnormalities in the gene PCSK9. The treatment reduced PCSK9 protein levels by 85% and LDL cholesterol by 56% in nonhuman primates for three years, Wilson's lab reported in Molecular Therapy in February.

RELATED:Moderna donates ultra-rare disease therapy to nonprofit founded by late Takeda R&D chief

The lab has been working with Precision Biosciences on that asset, which is ready to enter the clinic.As part of iECURE's deal with Wilson's lab, iECURE will conduct the phase 1 study and then return the program to Precision, Truitt said.

The next two indications in the pipeline are the rare metabolic disorders phenylketonuria and ornithine transcarbamylase deficiency, Truitt said.

The gene-editing technology used by iECURE and Wilson's lab is delivered viaadeno-associated virus, or AAV. Toxicity and safety issues have arisen with AAV gene therapies, which resulted in an FDA advisory committee meeting last week to discuss and make recommendations on animal and human testing with these therapies.

Wilson took part in two panels during thetwo-day meeting and said he doesn't see the results of that meeting having an impact on iECURE.

"In terms of the work with IECURE, there really isnt anything that I heard at the committee that impacts on our preclinical plan, our clinical plan or our discussions with health authorities," Wilson said.

Read more from the original source:
iECURE emerges with $50M to search for 'holy grail' and 'untapped frontier' of gene editing - FierceBiotech

Gene therapy experts Fulvio Mavilio, Ph.D., and Nicoletta Loggia, Ph.D., join as chief scientific officer and chief technical officer, respectively

Neuroscience and rare disease leader Leslie Meltzer, Ph.D., promoted to chief medical officer

Appointments reinforce companys strategic focus on innovation in the areas of discovery, clinical development and manufacturing

BOSTONandLONDON, Sept. 09, 2021 (GLOBE NEWSWIRE) -- Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader, today announced the appointment of two gene therapy and industry experts, Fulvio Mavilio, Ph.D., and Nicoletta Loggia, Ph.D., to serve as chief scientific officer and chief technical officer, respectively. The company also announced the promotion of Leslie Meltzer, Ph.D., who has been serving as senior vice president of medical affairs, clinical operations and diagnostics, to chief medical officer. Together, Drs. Mavilio, Loggia and Meltzer will oversee strategically important functions as Orchard continues to advance its later-stage portfolio and expand its hematopoietic stem cell (HSC) gene therapy pipeline into larger indications. We have seen the potentially transformative impact of our HSC gene therapy approach in devastating rare diseases and are now extending our focus on more prevalent conditions where there is a compelling rationale, said Bobby Gaspar, M.D., Ph.D., chief executive officer of Orchard Therapeutics. Fulvio, Nicoletta and Leslie all have proven track records in their respective areas of expertise, and their leadership in building our next-generation R&D and technical operations capabilities will be instrumental in accelerating our progress, advancing our pipeline and scaling our commercial infrastructure.

I have worked with many types of genetic medicine technology during my career and believe HSC gene therapy offers immense and distinct promise to correct the underlying cause of many severe diseases with a single treatment, said Dr. Mavilio. I am eager to begin working with this exceptional team to unlock the full potential of HSC gene therapy in new and larger indications.

I am excited to join Orchard at this vital juncture as we continue to invest in and scale our technical operations on a global level, said Dr. Loggia. "I look forward to working closely with our CMC teams and CDMO network to put in place innovative and efficient manufacturing solutions that will meet the needs of patients and our organization now and into the future.

Since joining Orchard more than three years ago, I have been proud to help cultivate the clinical, medical and operational capabilities that support our deep pipeline of investigational and approved HSC gene therapies, including five clinical-stage programs, said Dr. Meltzer. I look forward to partnering with our development and commercial teams to ensure a seamless integration and advance our portfolio through key anticipated milestones.

Drs. Loggias and Meltzers appointments are effective immediately. Dr. Mavilio has initially joined the company in a consulting capacity and will start full-time in January 2022.

About Fulvio Mavilio, Ph.D., chief scientific officer Dr. Mavilio will lead the companys discovery and translational research activities. In this capacity he will be responsible for expanding the companys pipeline into larger indications.

He joins Orchard Therapeutics from Smart Immune where he serves as chief scientific officer. Previously, Dr. Mavilio was senior vice president of translational science at Audentes Therapeutics in San Francisco, where he was responsible for advancing the companys pipeline from discovery to clinical development overseeing molecular biology, in vivo pharmacology, bioinformatics, and bioanalytics. Prior to joining Audentes, Dr. Mavilio was chief scientific officer of Genethon in vry, France from 2012 to 2017 where he led the development of a robust pipeline of gene therapy programs for blood, liver, and neuromuscular diseases. Earlier in his career, he held various positions at the Center for Regenerative Medicine of the University of Modena, Molmed SpA, Genera SpA, and the San Raffaele-Telethon Institute of Gene Therapy in Milan, Italy.

Dr. Mavilio is a member of the European Molecular Biology Association, past member of the Board of the American Society of Gene and Cell Therapy and a member of the editorial board of many international journals in the fields of genetics, molecular biology and gene therapy. Dr. Mavilio earned a Ph.D. in medical genetics at the University of Rome School of Medicine and has published more than 200 articles in major international journals. He also serves as Professor of Molecular Biology at the University of Modena and Reggio Emilia in Modena, Italy.

About Nicoletta Loggia, Ph.D., chief technical officer In her role, Dr. Loggia will be responsible for leading all aspects of technical operations, including process and analytical development, manufacturing, supply chain, engineering and CMC lifecycle management.

She joins Orchard Therapeutics from Novartis, where she held positions of increasing responsibility since 2004, most recently serving as global head of cell and gene therapies. In this role, Dr. Loggia led multidisciplinary international teams responsible for the end-to-end technical development, manufacturing and project management of several gene and cell therapies modalities, including lentiviral, adeno-associated virus (AAV), stem and CAR-T cell processes, from concept to commercialization. She also oversaw the integration of the CAR-T teams and AveXis AAV technical capabilities into Novartis technical R&D. Previously, Dr. Loggia was global head of technical development novel biologic entities and cell and gene therapies where she was responsible for the early phase development of biologics and gene therapies. Her broad industry experience encompasses global leadership in the development and manufacturing of sterile drug products and devices and approvals of several commercial assets.

A medicinal chemist by training, Dr. Loggia began her career in the biopharmaceutical industry as a formulation scientist at Pfizer. She earned her Ph.D. in pharmaceutical technologies from the University of Pavia in Italy. She is a registered pharmacist and member of the UK Royal and Italian Pharmaceutical societies. About Leslie Meltzer, Ph.D., chief medical officer Dr. Meltzer joined Orchard Therapeutics in June 2018 bringing extensive experience leading medical affairs for several premier biopharmaceutical companies. Throughout her career, Dr. Meltzer led integration of medical functions across brands including publication planning, field team training, advisory boards, patient registry and identification efforts, investigator-initiated trial prioritization and post-marketing planning. A neuroscientist by training, Dr. Meltzer has dedicated much of her career to advancing new therapies for difficult-to-treat brain diseases. During her tenure at the company, Dr. Meltzer has held positions of increasing responsibility, most recently serving as senior vice president of global medical affairs, diagnostics, clinical operations and data management.

She joined Orchard Therapeutics from Keryx Biopharmaceuticals (prior to its merger with Akebia Therapeutics) where she was the vice president of medical affairs supporting Auryxia (ferric citrate) for the treatment of chronic kidney disease. She previously served in various positions of increasing seniority in medical affairs at Biogen, where she led key elements of the U.S. launch and post-launch plan for Tecfidera (dimethyl fumarate) for the treatment of relapsing forms of multiple sclerosis. In recognition of her success and contributions, Dr. Meltzer was promoted to leadership roles in Biogens multiple sclerosis and then its hemophilia franchises, comprising the companys approved and investigational therapies. Dr. Meltzer began her career at Actelion (now part of Janssen) where she supported four approved and eight investigational therapies in a variety of therapeutic areas, including respiratory, cardiovascular, rheumatology, neurology and rare disease.

Dr. Meltzer earned her Ph.D. in neuroscience from Stanford University School of Medicine. About Orchard Therapeutics At Orchard Therapeutics, our vision is to end the devastation caused by genetic and other severe diseases. We aim to do this by discovering, developing and commercializing new treatments that tap into the curative potential of hematopoietic stem cell (HSC) gene therapy. In this approach, a patients own blood stem cells are genetically modified outside of the body and then reinserted, with the goal of correcting the underlying cause of disease in a single treatment.

In 2018, the company acquired GSKs rare disease gene therapy portfolio, which originated from a pioneering collaboration between GSK and the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy. Today, Orchard has a deep pipeline spanning pre-clinical, clinical and commercial stage HSC gene therapies designed to address serious diseases where the burden is immense for patients, families and society and current treatment options are limited or do not exist.

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

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

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

Other risks and uncertainties faced by Orchard include those identified under the heading "Risk Factors" in Orchards quarterly report on Form 10-Q for the quarter endedJune 30, 2021, as filed with theU.S. Securities and Exchange Commission(SEC), as well as subsequent filings and reports filed with theSEC. The forward-looking statements contained in this press release reflect Orchards views as of the date hereof, and Orchard does not assume and specifically disclaims any obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required by law.

Editors note: Auryxia and Tecfidera are registered trademarks of Akebia Therapeutics, Inc. and Biogen Inc., respectively.

Contacts

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

Media Benjamin Navon Director, Corporate Communications +1 857-248-9454 Benjamin.Navon@orchard-tx.com

Read more here:
Orchard Therapeutics Bolsters R&D and Technical Operations Leadership with New Executive ... - The Bakersfield Californian

PHILADELPHIA, Sept. 09, 2021 (GLOBE NEWSWIRE) -- Scout Bio today announced the successful completion of a CKD-associated anemia study in client owned cats treated with SB-001, an AAV expressing feline erythropoietin (fEPO). The study demonstrated a prolonged therapeutic effect with statistically significant increases in red blood cells after a single injection. SB-001 is the first gene therapy to successfully treat feline patients with an acquired non-monogenic disease. These results pave the way for Scout Bios portfolio of AAV delivered therapeutic proteins for companion animal diseases.

Clinical Study Highlights:

In this study we have successfully shown that SB-001 has the ability to increase PCV into the normal range, thereby reducing or eliminating the clinical effects of anemia associated with CKD, said Mark Heffernan, Ph.D., CEO of Scout Bio. These exciting results reinforce the potential for Scout Bios gene therapy platform to advance treatments for other acquired chronic diseases such as diabetes, chronic pain and atopic dermatitis.

There are no FDA-approved treatments available for CKD-associated anemia in cats. The single injection treatment of SB-001 presents an enormous advantage in convenience, improved compliance, and potentially allows owners more quality time with their pets. A new option for cats with kidney disease and anemia is urgently needed. These cats come into the veterinary clinic with weakness, lethargy, breathing difficulties, and overall feeling very unwell. SB-001s ability to increase the PCV can make a huge difference for many of these cats that would otherwise face euthanasia, said Anne Traas, DVM, MS, DACT, Chief Development Officer for Scout Bio and head of the clinical team leading the study. It was very rewarding to hear from owners participating in the study who expressed their deep gratitude for the additional time SB-001 was able to provide their beloved pets.

James M. Wilson, MD, PhD, Director of the Gene Therapy Program at the University of Pennsylvaniaand a co-founder of Scout Bio, commented, Scout Bios focus in companion animals with chronic diseases has resulted in this successful demonstration that AAV gene therapy can be an effective alternative to frequent injections with therapeutic proteins and result in the improvement of feline patient lives. These results provide validation that Scout Bios platform can be used to successfully deliver therapeutic proteins to treat chronic diseases in companion animals.

Scout Bio intends to progress key manufacturing activities and safety studies that will be necessary to apply for Expanded Conditional Approval under FDA guidelines.

About SB-001 SB-001 has a unique and innovative adeno-associated viral (AAV) vector, containing the gene for feline EPO, for delivery into the muscle cell nucleus which will continually produce therapeutic levels of the hormone. The expressed feline EPO stimulates erythropoiesis, or red blood cell production. The U.S. Food and Drug Administration (FDA) CVM has confirmed that SB-001 is eligible for Expanded Conditional Approval, potentially shortening the time until this product could be approved and made available.

About Chronic Kidney Disease (CKD)-Associated AnemiaAnemia associated with chronic kidney disease (CKD) in cats is a disease of high unmet medical need, with no FDA-approved therapies currently available. CKD is one of the most common diseases in senior cats and is an end-of-life disease that creates quality of life issues for cats and their owners. Up to 21% of cats with CKD have anemia and the only currently available therapeutic options are multiple blood transfusions or repeated injections of off-label human drugs. Compared to the off-label use of human EPO drugs, SB-001 is expected to have a superior safety profile with respect to immune reactions and incidence of pure red cell aplasia (PRCA), a serious life-threatening condition.

About Scout BioScout Bio is a biotechnology company revolutionizing pet medicine by delivering a pipeline of one-time gene therapies for major chronic pet health conditions. Scout Bios therapeutics are designed to induce long-term expression of therapeutic proteins in pet patients using AAV vector technology. Scout Bio has a research and development collaboration with the University of Pennsylvanias Gene Therapy Program, a leader in the field of genetic medicine research. Scout Bio is a private company headquartered in Philadelphia, Pennsylvania. For more information, seewww.scoutbio.co

University of Pennsylvania Financial DisclosureDr. Wilson is a Penn faculty member, scientific collaborator, key advisor, and co-founder of Scout Bio. As such, he holds an equity stake in the Company, his laboratory at Penn receives sponsored research funding from Scout Bio, and as an inventor of the licensed technology he may receive additional future financial benefits under licenses granted by Penn to Scout Bio. The University of Pennsylvania also holds equity and licensing interests in Scout Bio.

For further information, please contact:Fran GaconnierScout Bio214.417.4142 Fran.gaconnier@scoutbio.co

Link:
Scout Bio Successfully Completes Pilot Clinical Study of SB-001, a Single-Injection AAV Gene Therapy - GlobeNewswire

For the first time, doctors have partially restored the vision of a completely blind French man using light-sensing algae proteins. The breakthrough marks a significant milestone in genetic blindness treatment.

The man was diagnosed with the rare, genetic eye condition retinitis pigmentosa (RP) which causes the death of light-sensing cells on the retina forty years ago. The condition affects over two million people worldwide, and while complete blindness is rare, the man has had no vision for the past twenty years.

The French man, whose identity has not been revealed, was treated with optogenetics therapy, which uses the algae proteins to control cells at the back of his eye. He first realized the treatment was working when he could see the painted stripes of a crosswalk. Impressively, he can now count and grab objects too!

According to the study published on May 24 in Nature Medicine, this is the first reported case of partial functional recovery in a neurodegenerative condition after optogenetic therapy.

Optogenetics is a standard tool in fundamental neuroscience research, but its new to the world of medicine. It works by using light to activate specific brain cells and was used by the doctors in France to restore one of the mans eyes to detect light.

In his case, the light-detecting cells in his retina had died off a long time ago; therefore, the doctors inserted an algae gene into the surviving cells of the retina at the back of his eye. This caused them to produce channelrhodopsins, a protein found in algae that helps the photosynthetic microbes move toward light sources. In other words, now, when they are hit with light, they will send an electrical signal directly to the brain.

Since theres a big difference between photosynthetic algae and the human eye, the new therapy has limitations. It didnt restore the mans vision to normal levels and didnt allow him to see in color. However, they would respond to amber-colored light.

To solve this problem, the patient wore special goggles with a video camera and projector to capture the real world and translate a version in the correct wavelength onto the back of his eye, allowing him to see.

After months of training and building up high enough levels of the rhodopsins in the eye, the mans brain finally learned how to see again, starting with the white stripes of a pedestrian crossing.

Dr. Jos-Alain Sahel, who treated the patient at Pariss Institute of Vision, said:

This patient initially was a bit frustrated because it took a long time between the injection and when he started to see something. But when he started to report spontaneously that he could see the white stripes across the street, you can imagine he was very excited. We were all excited.

Not only did the patient report identifying the crosswalk, but that he could count the number of white stripes too! After more training, the patient displayed a significant improvement in daily visual activities, including detecting a mug, plate, phone, furniture in a room, or a door in a corridor, but only while using the goggles. Therefore, treatment by combining an optogenetic route with light-stimulating goggles led to a decent level of visual recovery.

While the mans eyesight isnt perfect, the difference between no vision and limited is a life-changer. The findings provide proof-of-concept that using optogenetic therapy to partially restore vision is possible, concluded Prof. Botond Roska from the University of Basel.

James Bainbridge, a retinal studies professor at the UKs UCL, said:

This exciting new technology might help people whose eyesight is very severely impaired.

Researchers are also exploring optogenetic therapy for conditions like Parkinsons disease to see whether it can improve recovery from a stroke.

In recent years, scientists have developed several approaches to restore sight. One includes correcting the genetic defects that cause RP, a challenging task since the disease has a significant number of mutations in over 71 different genes. In 2018, scientists at Oxford University in the UK completed a first gene therapy trial, improving patients vision for Choroideremia (one of the many forms of RP) by injecting a single healthy gene into their eyes. Their results were published in Nature Medicine.

Go here to read the rest:
Algae Gene Therapy Partially Restored Completely Blind Man's Vision - Intelligent Living