Category Archives: Gene Medicine

- PRGN-3007 is the first of the next generation UltraCAR-T, incorporating intrinsic PD-1 checkpoint inhibition in addition to the three effector genes used in the first generation UltraCAR-T technology -

Published: Oct. 26, 2021 at 8:05 AM EDT|Updated: 9 hours ago

GERMANTOWN,Md., Oct. 26, 2021 /PRNewswire/ -- Precigen, Inc. (Nasdaq: PGEN), a biopharmaceutical company specializing in the development of innovative gene and cell therapies to improve the lives of patients, today announced that the US Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application to initiate the Phase 1/1b clinical trial of PRGN-3007 in advanced receptor tyrosine kinase-like orphan receptor 1-positive (ROR1+) hematological and solid tumors. PRGN-3007 is a first-in-class investigational therapy based on the next generation of Precigen's UltraCAR-T platform and incorporates intrinsic programmed cell death protein 1 (PD-1) blockade. This first-in-human investigator-initiated study of PRGN3007 will be conducted in collaboration with the H. Lee Moffitt Cancer Center & Research Institute.

ROR1 is overexpressed in various cancers with minimal expression in healthy adult tissues. ROR1 is aberrantly expressed in multiple hematological tumors, including chronic lymphocytic leukemia (CLL), mantle cell leukemia (MCL), acute lymphoblastic leukemia (ALL), and diffuse large B-cell lymphoma (DLBCL) and solid tumors, including breast adenocarcinomas encompassing triple negative breast cancer (TNBC), pancreatic cancer, ovarian cancer, and lung adenocarcinoma.

PRGN-3007 UltraCAR-T is an investigational multigenic, autologous CAR-T cell therapy utilizing Precigen's clinically validated advanced non-viral gene delivery system and the well-established overnight, decentralized manufacturing process. Precigen has further advanced the UltraCAR-T platform to address the inhibitory tumor microenvironment by incorporating intrinsic checkpoint blockade without the need for complex and costly gene editing techniques. PRGN-3007 is engineered using a single multicistronic transposon plasmid to simultaneously express a chimeric antigen receptor (CAR) targeting ROR1, membrane-bound interleukin15 (mbIL15), a kill switch, and a novel mechanism for the intrinsic blockade of PD-1 gene expression.

The PD-1/programmed death ligand 1 (PD-L1) pathway plays a vital role in how tumor cells evade immune response. While the blockade of the PD-1/PD-L1 pathway has demonstrated considerable benefit for treating various cancers, the use of systemic checkpoint inhibitors can lead to side effects associated with autoimmune response. The innovative design of PRGN-3007, where the blockade of PD-1 expression is intrinsic and localized to UltraCAR-T cells, is aimed at avoiding systemic toxicity and the high cost of checkpoint inhibitors by eliminating the need for combination treatment.

The Phase 1/1b clinical trial is an open-label study designed to evaluate the safety and efficacy of PRGN-3007 in patients with advanced ROR1+ hematological (Arm 1) and solid (Arm 2) tumors. The target patient population for Arm 1 includes relapsed or refractory CLL, relapsed or refractory MCL, relapsed or refractory ALL, and relapsed or refractory DLBCL. The target patient population for Arm 2 includes locally advanced unresectable or metastatic histologically confirmed TNBC. The study will enroll in two parts: an initial 3+3 dose escalation in each arm followed by a dose expansion at the maximum tolerated dose (MTD). Arm 1 and Arm 2 will enroll in parallel.

"ROR1 is an attractive target for treatment of multiple hematological and solid tumors due to its high expression in cancer and minimal expression in healthy adult tissues," said Javier Pinilla-Ibarz, MD, PhD, Senior Member, Lymphoma Section Head and Director of Immunotherapy, Malignant Hematology Department, H. Lee Moffitt Cancer Center & Research Institute, and Principal Investigator for the PRGN-3007 clinical study. "Preclinical studies of PRGN-3007 UltraCAR-T indicate the potential for improved efficacy by specific targeting of ROR1 combined with intrinsic blockade of PD-1 expression and we look forward to investigating the potential in this first-in-human clinical study."

"ROR1 expression is thought to be a potential adverse prognostic factor in TNBC patients," said Hatem Soliman, MD, Medical Director of the Clinical Trials Office, H. Lee Moffitt Cancer Center & Research Institute, and Principal Investigator for the TNBC cohort of PRGN-3007 clinical study. "Given the aggressive nature of TNBC and the need for additional treatment options, we are eager to investigate PRGN-3007 in this setting."

"This is the first study of our next generation UltraCAR-T, which adds checkpoint blockade to our non-viral, multigenic UltraCAR-T platform," said Helen Sabzevari, PhD, President and CEO of Precigen. "PRGN-3007 eliminates the need to combine an antigen-specific CAR-T with a separate checkpoint inhibitor, which has the potential to avoid systemic toxicity and reduce cost. This new study is a big step toward our UltraCAR-T library approach, which aims to deliver personalized autologous UltraCAR-T therapies based on apatient's cancer indication and biomarker profile usingovernight manufacturingat the patient's medical center."

About Receptor Tyrosine Kinase-like Orphan Receptor 1 (ROR1)ROR1 is a type I orphan-receptor that is expressed during embryogenesis and by certain hematological and solid tumors but is undetectable on normal adult tissues.1-3 ROR1 plays an important role in oncogenesis by activating cell survival signaling events, particularly the non-canonical WNT signaling pathway.4 Aberrant expression of ROR1 is detected in multiple hematological malignancies including CLL5, MCL6, ALL7, and DLBCL.8 Elevated ROR1 expression is detected in various solid tumors, including breast adenocarcinoma encompassing TNBC, pancreatic cancer, ovarian cancer, Ewing's sarcoma and lung adenocarcinoma.9-14 Many human breast adenocarcinomas express high levels of ROR1, which is not expressed by normal breast tissue.15

Precigen: Advancing Medicine with PrecisionPrecigen (Nasdaq: PGEN) is a dedicated discovery and clinical stage biopharmaceutical company advancing the next generation of gene and cell therapies using precision technology to target urgent and intractable diseases in our core therapeutic areas of immuno-oncology, autoimmune disorders, and infectious diseases. Our technologies enable us to find innovative solutions for affordable biotherapeutics in a controlled manner. Precigen operates as an innovation engine progressing a preclinical and clinical pipeline of well-differentiated unique therapies toward clinical proof-of-concept and commercialization. For more information about Precigen, visit http://www.precigen.com or follow us on Twitter @Precigen and LinkedIn.

TrademarksPrecigen, UltraCAR-T and Advancing Medicine with Precision are trademarks of Precigen and/or its affiliates. Other names may be trademarks of their respective owners.

Cautionary Statement Regarding Forward-Looking Statements Some of the statements made in this press release are forward-looking statements. These forward-looking statements are based upon the Company's current expectations and projections about future events and generally relate to plans, objectives, and expectations for the development of the Company's business, including the timing and progress of preclinical studies, clinical trials, discovery programs and related milestones, the promise of the Company's portfolio of therapies, and in particular its CAR-T and AdenoVerse therapies. Although management believes that the plans and objectives reflected in or suggested by these forward-looking statements are reasonable, all forward-looking statements involve risks and uncertainties, including the possibility that the timeline for the Company's clinical trials might be impacted by the COVID-19 pandemic, and actual future results may be materially different from the plans, objectives and expectations expressed in this press release. The Company has no obligation to provide any updates to these forward-looking statements even if its expectations change. All forward-looking statements are expressly qualified in their entirety by this cautionary statement. For further information on potential risks and uncertainties, and other important factors, any of which could cause the Company's actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in the Company's most recent Annual Report on Form 10-K and subsequent reports filed with the Securities and Exchange Commission.

References

1Balakrishnan, A., et al., Analysis of ROR1 Protein Expression in Human Cancer and Normal Tissues. Clin Cancer Res, 2017. 23(12): p. 3061-3071.

2Green, J.L., et al., ROR receptor tyrosine kinases: orphans no more. Trends in Cell Biology, 2008. 18(11): p. 536-544.

3Rebagay, G., et al., ROR1 and ROR2 in Human Malignancies: Potentials for Targeted Therapy. Front Oncol, 2012. 2(34).

4Zhao Y, et al., Tyrosine Kinase ROR1 as a Target for Anti-Cancer Therapies. Front. Oncol, 2021.

5Baskar, S., et al., Unique Cell Surface Expression of Receptor Tyrosine Kinase ROR1 in Human B-Cell Chronic Lymphocytic Leukemia. Clin Cancer Res, 2008. 14(2): p. 396-404.

6Hudecek, M., et al., The B-cell tumorassociated antigen ROR1 can be targeted with T cells modified to express a ROR1-specific chimeric antigen receptor. Blood, 2010. 116(22): p. 4532-4541.

7Enayati H, et al., Expression of ROR1 Gene in Patients with Acute Lymphoblastic Leukemia. IJBC 2019; 11(2): 57-62.

8Ghaderi, A., et al., ROR1 Is Expressed in Diffuse Large B-Cell Lymphoma (DLBCL) and a Small Molecule Inhibitor of ROR1 (KAN0441571C) Induced Apoptosis of Lymphoma Cells. Biomedicines, 2020. 8(6).

9Zhang, S., et al., The onco-embryonic antigen ROR1 is expressed by a variety of human cancers. Am J Pathol, 2012. 181(6): p. 1903-10.

10Zhang, S., et al., ROR1 is expressed in human breast cancer and associated with enhanced tumor-cell growth. PLoS One, 2012.7(3): p. e31127.

11Potratz, J., et al., Receptor tyrosine kinase gene expression profiles of Ewing sarcomas reveal ROR1 as a potential therapeutic target in metastatic disease. Mol Oncol, 2016. 10(5): p. 677-92.

12Zheng, Y.Z., et al., ROR1 is a novel prognostic biomarker in patients with lung adenocarcinoma. Sci Rep, 2016. 6: p. 36447.

13Choi, M.Y., et al., Pre-clinical Specificity and Safety of UC-961, a First-In-Class Monoclonal Antibody Targeting ROR1. Clin Lymphoma Myeloma Leuk, 2015. 15 Suppl: p. S167-9.

14Balakrishnan, A., et al., Analysis of ROR1 Protein Expression in Human Cancer and Normal Tissues. Clin Cancer Res, 2017. 23(12): p. 3061-3071.

15Zhang S. et al., ROR1 is expressed in human breast cancer and associated with enhanced tumor-cell growth. PLoS One, 2012, 7:e31127.

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Precigen Announces Clearance of IND to Initiate Phase 1/1b Study for PRGN-3007 UltraCAR-T in Advanced ROR1+ Hematological and Solid Tumors - WAGM

The Genomic Revolution: Why Investors Are Paying Attention

At the center of the genomic revolution is big data and DNA.

The implications are vast. With recent advancements, faster cancer detection is within reach, potentially saving thousands of lives each year. An initial research study shows this technology could save 66,000 live annually in the U.S. alone.

Whats more, genomic innovation goes beyond just cancer detection. Today it spans a variety of innovations, from gene editing to anti-cancer drugs.

In this graphic from MSCI, we look at four reasons why the genomics sector is positioned for growth thanks to powerful applications in medicine.

To start, the genomic revolution focuses on the study of the human genome, a human (or organisms) complete set of DNA.

A human consists of 23 pairs of chromosomes and 24,000 genes. Taken together, the human genetic code equals three billion DNA letters. Since most ailments have a link to our genetic condition, genomics involves the editing, mapping, and function of a genome.

With genomic innovation, large-scale applications of diagnostics and decision-making tools are made possible for a wide range of diseases.

Over the last century, the field of genomics has advanced faster than any other life sciences discipline.

The hallmark achievement is the Human Genome Project completed in 2001. Since then, scientists have analyzed thousands of peoples genes to identify the cause of heart disease, cancer, and other fatal afflictions.

Here are four areas where genomic innovation is making a big difference in the medical field.

Gene editing enables scientists to alter someones DNA, such as eye color. Broadly speaking, gene editing involves cutting DNA at a certain point and adding to, removing, or replacing this DNA.

For instance, gene editing enables living drugs. As the name suggests, living drugs are made from living organisms that harness a bodys immune system or other bodily process, and uses them to fight disease.

Based on analysis from ARK Invest, living drugs have a potential $200 billion addressable market.

Multi-cancer screening, supported by genomic sequencing and liquid biopsies, is projected to prevent more deaths from cancer than any other medical innovation.

Through a single blood test, multiple types of cancer can be detected early through synthetic biology advancements. Scientists use genomic sequencing (also referred to as DNA sequencing) to identify the genetic makeup of an organism, or a change in a gene which may lead to cancer.

Critically, screening costs are dropping rapidly, from $30,000 in 2015 to $1,500 in 2021. The combination of these factors is spurring a potential $150 billion market. This could be revolutionary for healthcare by shifting from a treatment-based model to a more preventative one in the future.

One modern form of DNA sequencing is long-read DNA sequencing. With long-read DNA sequencing, scientists can identify genetic sequences faster and more affordably.

For these reasons, long-read DNA sequencing is projected to grow to a $5 billion market, growing at a 82% annual rate.

Finally, the genomic revolution is making strides in agricultural biology. Here, research is looking at how to reduce the cost of producing crops, improving plant breeding, and enhancing quality.

One study shows that genomic advances in agriculture have led to six-fold increases in income for some farmers.

A number of genomic-focused companies have shown promising returns.

This can be illustrated by the MSCI ACWI Genomic Innovation Index, which has outperformed the benchmark by nearly 50% since 2013. The index, which was developed with ARK Invest, comprises roughly 250 companies who are working in the field of genomic innovation. In 2020 alone, the index returned over 43%.

From diagnostics to prevention, the genomic revolution is breaking ground in scalable solutions for global health. Investment opportunities are expected to follow.

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5 Trends Shaping the Future of eCommerce - Visual Capitalist

Scientists are learning more and more about human biological variation, including of sex characteristics. But images of the human body in anatomy remain mostly muscular, white, and male with limited diversity, including of sex.

Intersex people represent just under 2% of the population a comparable percentage to people born with red hair. Yet anatomy textbooks used in Australian medical schools almost completely stick to the male-female sex binary. In our earlier research we found intersex was included in only five of 6,004 images across 17 texts. This marginalises intersex people, who have been persistently discriminated against within the health-care system.

The intersex community is the often forgotten I in LGBTQI+. Intersex Human Rights Australia highlights the need for increased visibility and to prevent unnecessary surgeries. Now there are fresh calls for health and medical students to learn about sex characteristics as a continuum rather than as male or female.

Read more: Marriage equality was momentous, but there is still much to do to progress LGBTI+ rights in Australia

Sex development in utero is complex, involving at least 70 different genes.

Our sex is defined by our genes (Y or X chromosome), gonads (ovaries or testes), reproductive tract, and external genitalia.

Whether a foetus develops female, intersex or male characteristics is determined by four key elements. These are the Y chromosome and its sex-determining gene (SRY gene), and two hormones (anti-Mullerian hormone and testosterone).

A foetus with all four elements will develop male sex characteristics.

At 67 weeks gestation, the SRY gene on the Y chromosome signals the gonads to develop into testes. About 23 weeks later, secretion of two hormones by the testes directs further sex development. Anti-Mullerian hormone stops female sex characteristic development. Testosterone stimulates development of the male reproductive tract and external genitalia.

When all four elements are absent, female sex characteristics develop.

Without a Y chromosome and its SRY gene, the gonads develop into ovaries. Without anti-Mullerian hormone or testosterone production, the female reproductive tract and external genitalia develop.

The presence of some but not all of these elements results in the development of intersex characteristics.

Intersex can include both or a combination of male and female sex characteristics, depending on variations in chromosomes, genes or hormones. This represents the continuum of the sex spectrum between the male and female binaries.

Known variations in the Y and X chromosomes include XY (genetic male), XXY (Klinefelter syndrome), X (Turner syndrome), XX (genetic female). Variations in the gonads include the presence of both ovaries and testes, or only partial development of either. Other intersex variations include a combination of male and female genitalia, and external genitalia that differs in sex to the genetic sex.

Intersex traits are not always visible at birth. Individuals may not realise they are intersex until puberty, or only if they undergo assessment for infertility or genetic testing.

There is a tragic history of irreversible surgical interventions in intersex infants and children. This was often without their consent, or with parents coerced to consent.

These surgeries have been to normalise external genitalia to a male or female binary. The impact of these procedures may violate human rights. They can be devastating for intersex peoples lifelong physical and mental well-being.

The UN Office of the High Commissioner for Human Rights description of intersex is having sex characteristics that do not fit typical binary notions of male or female bodies. But even this pathologises intersex by indicating that intersex people do not fit.

Normalisation of sex variation and increased visual representation of intersex in anatomy is necessary to reduce stigma.

The minimal visual representation of intersex people in anatomy textbooks can affect students attitudes towards this. We have previously found viewing gender-biased images of anatomy is associated with higher implicit gender bias. Todays students are our next generation of doctors and health-care workers.

Read more: What are gender pronouns and why is it important to use the right ones?

Teaching sex characteristics based on a male-female binary is inaccurate and outdated. Weve also shown it negatively influences the healthcare of intersex individuals.

Both the University of Wollongong and the University of New South Wales are developing inclusive anatomy curricula within their medicine and health degrees. Harvard Medical School and University of British Columbia are also developing online, accessible resources to promote inclusive anatomical representation in medical education.

Inclusive teaching and knowledge of sex variation can be transformative beyond anatomy.

Teaching sex characteristics as a continuum will increase the visibility and understanding of intersex. Removing the stigma associated with sex (and other) variations in anatomy, and medical and health education is essential for optimal health, well-being, belonging and connection for everyone.

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Anatomy texts should show sex as a spectrum to include intersex people - The Conversation AU

Angelman syndrome affects roughly 1 in every 20,000 children and it has no approved treatment.

Researchers recently published results of early tests of a gene therapy strategy for Angelman syndrome, a rare neurodevelopmental disorder that features poor muscle control and balance, hard-to-treat epilepsy, and intellectual disabilities.

Angelman syndrome affects roughly 1 in every 20,000 children. In United States there may be more than 15,000 people with the condition and it has no specific treatment.

The genetics of Angelman syndrome are more complicated than classic single-gene disorders such as cystic fibrosis and sickle cell anemia. Humans inherit 1 maternal and 1 paternal copy of most genes. Angelman syndrome arises in children whose maternal UBE3A copy has somehow been mutated or deleted.

For reasons that arent fully clear, mature neurons normally express only the maternal copy of UBE3A; the paternal copy is effectively silenced. Thus, when the maternal copy is lost, the genes function is absent in neurons. Because UBE3A encodes a protein that helps regulate the levels of other important proteins, its absence severely disrupts brain development.

Compounding the complexity, neurons express 2 different variants or isoforms of UBE3A that vary slightly in lengtha short form and a long formin a ratio of about 3 short forms for every 1 long form.

Researchers created a version of UBE3A that, when expressed by neurons, yields short and long forms of the UBE3A protein at a near-normal ratio. The scientists inserted their therapeutic UBE3A gene into a virus-based vector engineered for reliable delivery to neurons. They injected a solution of this vector into hollow spaces, called ventricles, in the brains of newborn Angelman syndrome model mice, which lack the maternal copy of the mouse Ube3a gene. Like humans with Angelman syndrome, these mice fail to express UBE3A protein in their neurons and develop motor deficits, seizures, and other neurological symptoms in the first months of life.

The scientists verified that vector-borne UBE3A became active in neurons throughout the Angelman model mouse brain just days after injection, at a level similar to that of the normal gene. This treatment restored motor skill-learning and the essential mouse behaviors of digging, burrowing, and nest-building. Untreated mice developed the usual Angelman-like impairments. The treated mice also did not become as susceptible as their untreated counterparts to experimentally induced epileptic seizures, and importantly, did not suffer any obvious negative side effects.

This was a proof-of-concept study, but if these early results were translated to the clinic, they would represent big improvements in the quality of life for individuals with Angelman syndrome, said study lead author Matt Judson, PhD, a research associate in the Philpot Lab at the University of North Carolina School of Medicine.

Results were published in the journal JCI Insight.

The researchers plan to further develop their strategy in additional animal models to optimize dose and delivery methods, and ultimately human clinical trials. If such a therapy were available, the researchers expect it might be able to deliver benefits to individuals of any age, but perhaps with varying benefits.

Reference

Judson MC, Shyng C, Simon JM, et al. JCI Insight. Published online October 22, 2021. doi:10.1172/jci.insight.144712.

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Early Results of Gene Therapy for Angelman Syndrome Look Promising - AJMC.com Managed Markets Network

THURSDAY, Oct. 21, 2021 (HealthDay News) -- Nine of 10 patients with so-called "bubble boy" immune disease who received gene therapy about a decade ago are still disease-free, researchers report.

The gene therapy was developed at the University of California, Los Angeles (UCLA), to treat the rare and deadly immune system disorder formally known as adenosine deaminasedeficient severe combined immunodeficiency (ADA-SCID).

It's caused by mutations in the gene that creates the ADA enzyme, which is crucial for a normally functioning immune system. Exposure to common germs can be fatal for babies with the disease. If untreated, most die within the first two years of life.

With the UCLA gene therapy, blood-forming stem cells are removed from a child's bone marrow and a specially modified virus is used to place healthy copies of the ADA gene into the stem cells' DNA. The cells are then transplanted back into the child's bone marrow.

The therapy is meant to prompt the body to produce a continuous supply of healthy immune cells that can fight infections. The transplanted stem cells are the child's own, so there is no risk of rejection.

Now, in the study published Oct. 14 in the journal Blood, the UCLA researchers reported that nine of the 10 children who received the one-time treatment between 2009 and 2012 as part of a phase 2 clinical trial remain stable.

Most of the children were babies at the time they received the gene therapy. The only one whose immune function wasn't restored by the gene therapy was 15 at the time of treatment.

"What we saw in the first few years was that this therapy worked, and now we're able to say that it not only works, but it works for more than 10 years," senior study author Dr. Donald Kohn, with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, said in a UCLA news release. "We hope someday we'll be able to say that these results last for 80 years."

Gene therapy for ADA-SCID is not yet approved by the U.S. Food and Drug Administration.

Without it, children with ADA-SCID have to receive twice-weekly expensive and time-consuming injections of the ADA enzyme, or receive a transplant of healthy stem cells from a matched bone marrow donor.

In this study, patients with more copies of the ADA gene in more cells had the best immune function. More research is needed to determine the best way to achieve high levels of the gene in all patients, according to Kohn, a distinguished professor of microbiology, immunology and molecular genetics.

"What these results tell us is that there's a formula for optimal success for ADA-SCID, and it involves correcting more than 5% to 10% of each patient's blood-forming stem cells," he said.

"Knowing that a gene therapy can have this lasting effect in ADA-SCID for more than a decade is important for our path forward as we develop new gene therapies for this and other diseases," Kohn added.

More information

The U.S. National Library of Medicine has more on ADA-SCID.

SOURCE: University of California, Los Angeles, news release, Oct. 15, 2021

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Ten Years On, Gene Therapy Still Beating Most Cases of 'Bubble Boy' Immune Disease - HealthDay News

SOUTH SAN FRANCISCO, Calif., October 21, 2021--(BUSINESS WIRE)--Graphite Bio, Inc. (Nasdaq: GRPH), a clinical-stage, next-generation gene editing company focused on therapies that harness targeted gene integration to treat or cure serious diseases, announced today that members of the management team will participate in a fireside chat at the Jefferies Gene Therapy/Editing Summit on Thursday, Oct. 28, 2021, at 4:30 p.m. ET.

The fireside chat will be webcast live from Graphite Bios website at http://www.graphitebio.com in the Investors section. A replay of the webcast will be archived and available for one month following the event.

About Graphite Bio

Graphite Bio is a clinical-stage, next-generation gene editing company harnessing high efficiency targeted gene integration to develop a new class of therapies to potentially cure a wide range of serious and life-threatening diseases. Graphite Bio is pioneering a precision gene editing approach that could enable a variety of applications to transform human health through its potential to achieve one of medicines most elusive goals: to precisely "find & replace" any gene in the genome. Graphite Bios platform allows it to precisely correct mutations, replace entire disease-causing genes with normal genes or insert new genes into predetermined, safe locations. The company was co-founded by academic pioneers in the fields of gene editing and gene therapy, including Maria Grazia Roncarolo, M.D., and Matthew Porteus, M.D., Ph.D.

Learn more about Graphite Bio by visiting http://www.graphitebio.com and following the company on LinkedIn.

View source version on businesswire.com: https://www.businesswire.com/news/home/20211021005108/en/

Contacts

Company: Stephanie YaoVP, Communications and Investor Relations443-739-1423syao@graphitebio.com

Investor Relations: Stephanie AscherStern IR, Inc.212-362-1200ir@graphitebio.com

Media: Christy CurranSam Brown, Inc.615-414-8668media@graphitebio.com

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Graphite Bio Announces Participation in Upcoming Jefferies Gene Therapy/Editing Summit - Yahoo Finance

DetailsCategory: DNA RNA and CellsPublished on Saturday, 23 October 2021 11:49Hits: 435

Sub-retinal delivery of closed-ended DNA (ceDNA) using a retina-specific cell-targeted LNP (ctLNP) demonstrated broad photoreceptor distribution, durable expression and tolerability in rodents; potential to address inherited retinal diseases with full gene replacement

Uniform retinal transduction and tolerability also demonstrated for ctLNP delivery of mRNA following sub-retinal injection in non-human primates; potential best-in-class non-viral delivery of mRNA for gene editing in the retina

CAMBRIDGE, MA, USA I October 22, 2021 I Generation Bio Co. (Nasdaq: GBIO), a biotechnology company innovating genetic medicines for people living with rare and prevalent diseases, today presented new preclinical data demonstrating widespread delivery of multiple nucleic acid cargos to photoreceptors using the companys cell-targeted lipid nanoparticle (ctLNP). The findings were shared in an oral presentation at the European Society of Gene and Cell Therapy (ESGCT) 2021 Annual Virtual Congress.

Were excited to extend the benefits of ourhighly specific, cell-targeted LNP totheretina, wherenon-viral delivery of nucleic acids has long been held back bypoor tolerabilityandlow expression. Ourability to selectively delivermultiplenucleic acid cargosto the retinausingctLNPmay allow ustoaddress a variety ofinherited retinal diseasesusing full gene replacement or gene editing,saidMatthew Stanton, Ph.D., chief scientific officer of Generation Bio.

Sub-retinal delivery of Generation Bios proprietary closed-ended DNA (ceDNA) using ctLNP demonstrated broad photoreceptor distribution and durable expression in rodents. Expression was comparable to AAV5 delivery, and ctLNP-ceDNA was well-tolerated without evidence of photoreceptor degeneration, supporting the potential for full gene replacement to address inherited retinal diseases.

Data were also presented for sub-retinal delivery of mRNA using ctLNP, representing the first-ever demonstration of species translation from rodents to non-human primates with tolerability and uniform photoreceptor expression. Distribution with ctLNP was broader and more uniform than that achieved with AAV5 in mice, and total expression was comparable to AAV5. These findings suggest ctLNP as a best-in-class non-viral delivery system for mRNA, potentially enabling gene editing in the retina.

Diseases such as Stargardt cannot be addressed with traditional viral-based genetic therapies due to the limited cargo capacity of the viral vector. We believe these data using our non-viral genetic medicine platform provide a promising path to treat this challenging disease and others like it, and may expand our platforms potential to enable multiple therapeutic modalities, including full gene replacement and gene editing, said Tracy Zimmermann, Ph.D., chief development officer of Generation Bio. "We are excited for the potential for our non-viral delivery technology to expand therapeutic opportunities in the retina as well as to target other tissue types for the treatment of a broad range of diseases.

To view the digital presentation, please visit Generation Bios website.

About Generation BioGeneration Bio is innovating genetic medicines to provide durable, redosable treatments for people living with rare and prevalent diseases. The companys non-viral genetic medicine platform incorporates a novel DNA construct called closed-ended DNA, or ceDNA; a unique cell-targeted lipid nanoparticle delivery system, or ctLNP; and a highly scalable capsid-free manufacturing process that uses proprietary cell-free rapid enzymatic synthesis, or RES, to produce ceDNA. The platform is designed to enable multi-year durability from a single dose, to deliver large genetic payloads, including multiple genes, to specific tissues, and to allow titration and redosing to adjust or extend expression levels in each patient. RES has the potential to expand Generation Bios manufacturing scale to hundreds of millions of doses to support its mission to extend the reach of genetic medicine to more people, living with more diseases, around the world.

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

SOURCE: Generation Bio

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Generation Bio Presents Data Demonstrating First Lipid Nanoparticle to Achieve Uniform Retinal Transduction and Tolerability via Sub-Retinal Delivery...

Published: Oct. 20, 2021 at 8:00 AM EDT

SAN DIEGO, Oct. 20, 2021 /PRNewswire/ --ViaCyte, Inc., an innovator in cellular therapy and regenerative medicine, announced today that Michael Yang, President & CEO, will present at the Jefferies Gene Therapy/Editing Summit on Wednesday, October 27, 2021 at 11:30 a.m. ET. Mr. Yang will highlight progress with the Company's investigational pancreatic islet cell replacement therapies, including its program focused on the development of gene-edited immune evasive cells for the treatment of diabetes.

A live webcast of this presentation will be available on the Company's News & Events page accessible here: https://viacyte.com/news-events/. A replay will be available on the Company's website following the event.

About ViaCyteViaCyte is a privately held clinical-stage regenerative medicine company developing novel cell replacement therapies based on two major technological advances: cell replacement therapies derived from pluripotent stem cells and medical device systems for cell encapsulation and implantation. ViaCyte has the opportunity to use these technologies to address critical human diseases and disorders that can potentially be treated by replacing lost or malfunctioning cells or proteins. The Company's first product candidates are being developed as potential long-term treatments for patients with type 1 diabetes to achieve glucose control targets and reduce the risk of hypoglycemia and diabetes-related complications. To accelerate and expand the Company's efforts, ViaCyte has established collaborative partnerships with leading companies, including CRISPR Therapeutics and W.L. Gore & Associates. ViaCyte is headquartered in San Diego, California. For more information, please visitwww.viacyte.comand connect with ViaCyte onTwitter,Facebook, andLinkedIn.

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ViaCyte to Present at the Jefferies Gene Therapy/Editing Summit - WCAX

Nonclinical development to advance promising Gene Therapies often require the use of novel animal models to prove efficacy and/or safety.This webinar will frame the basis of typical nonclinical study needs to advance gene therapies from concept to clinic; with consideration of regulatory guidance and science in the design of experiments that may be considered by the FDA. The presentation will frame the overall regulatory and scientific constructs that are 'typical', and use cystic fibrosis as a hallmark example of the use of various animal model approaches to evaluate safety and efficacy for therapeutics, including a discussion of drug delivery and non-pulmonary safety evaluation.

Register for the webinar here: https://www.webcaster4.com/Webcast/Page/2117/43201

Speakers

Dr. Jake McDonald is a Senior Scientist and Vice President of Applied Science at Lovelace Biomedical.In this role he serves as Director and Technical Advisor to collaborators in the design and execution of nonclinical development packages related to toxicology and pharmacology.Much of his emphasis is in the development of Gene Therapy technologies under GLP to support IND submissions. Dr. McDonald will present on the framework for the use of rare disease models and regulatory considerations for safety.

Dr. John Engelhardt is Professor and Chair of the Department of Anatomy and Cell Biology and Director of the Center for Gene Therapy at the University of Iowa Roy J. and Lucille A. Carver College of Medicine. His research focuses on the following areas: 1) the study of the molecular and cellular pathogenesis of cystic fibrosis (CF) related diabetes and lung disease, 2) the study of airway and pancreatic stem cells, 3) the development of animal models of CF lung and pancreatic diseases, and 5) the development of gene therapies for CF with a focus on recombinant parvoviruses and their transduction biology.

About Lovelace BiomedicalLovelace Biomedical is a contract research organization that conducts research to advance pharmaceutical and biotechnology companies in their complex drug development studies from the preclinical stage, and on to clinical trials. For over 70 years, the organization has leveraged its multidisciplinary expertise in toxicology, gene therapy, neurological disorders, infectious disease, and medical countermeasures.

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Original post:
Lovelace Biomedical Presents a New Webinar on Rare Diseases and Gene Therapy Preclinical Research - PRNewswire

When Novartis reported first-half Zolgensma sales this summer, the company said its spinal muscular atrophy (SMA) gene therapy was growing thanks to"expanding access" in Europe. This week at the Fierce Biotech Cell & Gene Therapy event, an exec outlined what's driving the uptake.

So far, Novartis has negotiated Zolgensma access for half of the SMA patient population in Europe, including for patients inEngland,Scotland, France, Germany, Italy, Belgium and other countries,Mike Fraser,general manager of Europe, Middle East and Africa at Novartis Gene Therapies, said in an interview.Novartis also has deals in place with six countries in the Middle East and Africa, he added.

Zolgensma scored its FDA approval in 2017 and its EU nod in 2020. Even ahead of the EU approval, Novartis was working behind the scenes to ensure a quick rollout in the region.

In some countries, it can take months or years for access negotiations to play out, Fraser said. Babies with SMA dont have time to wait, he added.

To hit the ground running, the company implemented a day one" access program. In government access negotiations, Novartis offered outcomes-based contracting, annuity payments or deferred payments, in which the company would cover the cost of treatment upfront and collect payments after access talks play out.

RELATED:New Zolgensma 'inflection point' is here as Novartis snags EU nod for SMA gene therapy

While Novartis has seen progress, Fraser still sees limitations with current healthcare systems. As he sees it, healthcare systems "are still not set up to recognize the value of these one-time therapies."That's despite the fact that expensive gene therapies can bring savings over a patient's life compared withconventional medicines.

By 2030, Fraser said he expects more than 20 gene therapies to be on the market.While Novartis is on the cutting edge of interacting with payers, he urged other companies to start getting involved in their own access talks.

One lesson for Novartis? Because healthcare and financialsituations vary from country to country, the pharmaceutical industry is going to have to get used to offering" a range of access options, Fraser said.

With these new and innovative treatments, bespoke and customized solutions are going to be the future, Fraser said.

Aside from access talks, Novartis is also participating in an effortto screen babies for SMA. Through a partnership with SMA Europe, the pharmaceutical industry aims to screen 100% of newborns across Europe by 2025.

RELATED:Novartis back with bid for 'multibillion-dollar' Zolgensma expansion in older SMA patients as FDA lifts clinical hold

The European approval of Zolgensma last year wasone "inflection point" that Novartis had been anticipating for the gene therapy since its original FDA nod. Meanwhile, the company is advancing aspinal injection formulation for patients between twoand 18 years. A potential approval for that use represents a "multibillion-dollar" opportunity, CEO Vas Narasimhan has said.

Zolgensma generated $634 millionduring the first half of the year, a 69% increase compared with 2020. The medicine is approved in more than 40 countries.

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Novartis has negotiated Zolgensma access for half of the European SMA population, exec says. How'd it get there? - FiercePharma