RESEARCH TRIANGLE PARK The Triangle continues to emerge as a hotbed of life science and biopharmaceutical technologies, along with a global evolution in medicine,Paul Garofolo, the cofounder and chief executive officer for Locus Biosciences, tells WRAL TechWire.

There is a revolution occurring in medicine. We are evolving from the days where we discovered small molecules that produced a favorable result in a large number of patients, likely with some level of side effects, to precision medicines that directly address the problem for the intended patient, he says. It started with antibodies and other biologic therapies that revolutionized Oncology and Immunological diseases. It is moving towards cell and gene therapies where the technology is proving itself in ultrarare diseases, and much like their predecessor technologies, will move toward more broad-based applications over time.

And Locus expects to be a part of the future of medicine, having grown its workforce to 75 employees since the companys founding in 2015, after Garofolo had the CRISPR-Cas3 technology upon which the companys research is built introduced to him by a student at North Carolina State University.

Theres growth ahead, as well, said Garofolo, as the company expects to reach 100 employees in 2022, and recently landed a $25 million credit facility to expand the companys in-house manufacturing capabilities and drug discovery program.

Paul Garofolo. Locus Biosciences image.

Were unique in biopharma in that we are clinical stage and revenue generating, said Garofolo. We generate revenue from our partnerships with two of the top five global pharmaceutical companies and contracts with BARDA and CARB-X, which together provide a combination of milestone payments, R&D cost reimbursement, and manufacturing revenue.

Those partnerships, the first of which was signed in 2019 with Janssen Pharmaceuticals, also known as Johnson & Johnson, are worth as much as $1 billion.

That partnership with Johnson & Johnson yielded Locus $20 million up front and up to $798 million in potential development and commercial milestones, as well as royalties on product sales, said Garofolo, with the goal of the partnership being the development and manufacturing ofcrPhage products targeting two key bacterial pathogens.

The company signed a contract with the Biomedical Advanced Research and Development Authority (BARDA) in September 2020 that enabled the company to advance a $144 million precision medicine program to develop LBP-EC01, a crPhage product, to combat recurrent urinary tract infections caused by E. coli,, and later that year, the company inked a deal worth $15 million to develop a product to combat antibiotic-resistant K. pneumoniae infections through Phase 1 of clinical development with the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X).

Garofolo told WRAL TechWire that he and his wife provided the initial funding for the company, then raised a seed round of $1.5 million in 2016, a $19 million Series A round in 2017, a convertible note of $20 million in 2020, and then the recent $25 million credit facility earlier this year. That positions the company for the future, Garofolo noted, adding that this access to valuable growth capital supporting the expansion of our discovery platform engine and in-house manufacturing capacity [will be] used to address critical unmet medical needs.

WRAL TechWire spoke with Garofolo about the company, and about the future of life science and biopharma. A lightly edited transcript of the conversation appears below.

Inside Locus Biosciences $25M capital plan: What startup plans to do

TW: Tell us more about Locus Biosciences, its six programs, and the companys position in the marketplace.

Garofolo: Locus is the worlds leading developer of products based on CRISPR-Cas3 systems. Were unique in biopharma in that we are clinical stage and revenue generating. As described above, we generate revenue from our partnerships with two of the top five global pharmaceutical companies and contracts with BARDA and CARB-X, which together provide a combination of milestone payments, R&D cost reimbursement, and manufacturing revenue.

Locus has one clinical program underway, and up to five more in urinary tract, respiratory and bloodstream infections anticipated to enter the clinic by 2023.

Locuscompletedthe worlds firstplacebo-controlled Phase 1bclinical trial of a CRISPR Cas3-enhanced bacteriophage product targetingE. coliin UTIs. The results demonstrated safety and tolerability for LBP-EC01, and the trial met all its primary and secondary endpoints. We are working towards initiating the LBP-EC01 Phase 2 study inearly 2022. In October 2020, Locus announced a contract with the Biomedical Advanced Research and Development Authority (BARDA) to support Phase 2 and Phase 3 clinical trials and other activities required to seek FDA approval of LBP-EC01.

In 2019, Locus announced an agreement with Janssen Pharmaceuticals, Inc. for an exclusive, worldwide research collaboration and license to develop, manufacture and commercialize two products generated using Locuss recombinant CRISPR-Cas3 engineered bacteriophage (crPhage) platform for the treatment of respiratory tract infections which cause significant morbidity and mortality. The collaboration focuses on developing unique bactericidal disease-modifying crPhage products. These products will treat serious respiratory tract infections and infections in other areas of the body.

RTPs Locus Biosciences secures up to $25M in credit, plans expansion

TW: Whats the difference betweenCRISPR-Cas9 and CRISPR-Cas3 in the context of CRISPR technology overall?

Garofolo: CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is the adaptive immune system of bacterial cells, capable of capturing and incorporating an invaders DNA into the bacterias genome to fend off future attacks.

When reprogrammed, as Locus has done, CRISPR enzymes like Cas3 and 9 can be used to edit or destroy DNA, making it a very useful tool for gene therapy, antibacterials, and other applications.

CRISPR-Cas3 is the most common CRISPR-Cas system in nature. Cas3 is a powerful exonuclease that permanently degrades chromosomal DNA beyond repair with high specificity, leading to rapid death of the target bacterial cell. Cas3s DNA degrading effect is distinct from the more widely-known Cas9 which causes a clean break in the DNA that can be repaired by the cell.

While others use CRISPR-Cas9 to edit DNA in human cells and other organisms, Locus is concentrating its efforts on removing deadly pathogens from the human body. CRISPR-Cas3, loaded into a bacteriophage delivery vehicle (other gene therapy companies use AAV), is the ideal system to target DNA to destroy a bacterial cells genome beyond repair.

Simply put, Cas3 acts like a Pacman that gobbles up tens of thousands of DNA base pairs while Cas9 acts like a pair of scissors that make a precise cut in one place.

Genetically enhanced antibiotic from RTP firm advances in first-of-its-kind clinical trial

TW: The company describes on its website and in press statements two product lines, precision bacteriophage products and also engineered bacteriophage therapies. Tell us more about each, and the science behind the product lines.

Bacteria are directly associated with many human diseases. Bacteriophages, or phages, are naturally occurring viruses that infect and kill bacteria. Bacteriophage have been used as antibacterial therapy for more than 100 years. However, natural phages are not typically effective enough on their own to treat serious infections in humans. Locus believes its precision engineered bacteriophage platform has the potential to fundamentally change the way bacteria-related diseases are treated.

Our team of scientists collects natural bacteriophagethe natural predator of bacteriawith the best disease-fighting characteristics. Then, leveraging artificial intelligence and machine learning algorithms, Locus Biosciences identifies the best cocktail of bacteriophages to target a particular bacterial species that causes a specific disease. Next, we engineer these bacteriophages with CRISPR-Cas3, which drastically increases their ability to fight bacteria and treat diseases without killing the good bacteria the body needs without applying selective pressure to other bacteria that increases AMR (antimicrobial resistance)

Through its unique bacteriophage discovery, synthetic biology and manufacturing platform, Locus is developing two innovative categories of biotherapeutics to address significant unmet medical needs: precision products to fight deadly infections, including those caused by multi-drug resistant bacteria; and engineered bacteriophage therapies that utilize bacteria resident in the body to deliver therapeutic molecules, while leaving the rest of the microbiome intact. Both categories are engineered bacteriophage. The former, are CRISPR Cas3-enhanced bacteriophage (crPhage) that exquisitely eradicates bacteria. While developing crPhage we became experts in engineering bacteriophage, where we can now deliver any protein or peptide therapeutic we desire.

The incidence of antibiotic-resistant infections is growing rapidly with large-scale use of antibiotics. This is a particular concern with the overuse of antibiotics during a viral pandemic, such as those caused by H1N1 influenza or SARS-CoV-2.

Gene editing success could turn Triangle startup Locus Biosciences into a billion dollar unicorn

The need for new precision antibacterial therapies that selectively kill target bacteria while leaving good bacteria in the body unharmed is widely recognized. The development of non-traditional therapies that possess alternative properties to conventional small-molecule antibiotics represents a unique opportunity to advance the field of medicine and provide new treatment options to patients with antimicrobial-resistant infections which are a growing concern for our nations health security.

Furthermore, the one bug, one drug precision approach our platform employs, has significant implications for bacterial infections in patients receiving novel therapeutics for conditions such as cancer. Lifesaving checkpoint inhibitors, for example, which are used across several cancer types, are negatively impacted by antibiotic use in these fragile patients. By specifically targeting only the pathogen of interest, Locus precision medicines avoid negatively affecting patient responses to these important therapies.

Within immunology and oncology, the association between disease and bacteria is becoming clearer each day. Locus platform enables the company to directly remove bacteria driving/exacerbating disease while delivering biotherapeutics that can ameliorate disease pathogenesis.

Here we leverage the microbiome to manufacture the biotherapeutics inside the human body at the site of the disease, increasing the effective dose at the target site while decreasing systemic exposure. All designed to improve outcomes while decreasing side effects.

Gene editing firm Locus Biosciences adds another $7M to its 2020 cash haul

TW: Whats the current state of the industry and the sector, and what does the future hold, in 2022 and beyond?

Garofolo: There is a revolution occurring in medicine. We are evolving from the days where we discovered small molecules that produced a favorable result in a large number of patients, likely with some level of side effects, to precision medicines that directly address the problem for the intended patient. It started with antibodies and other biologic therapies that revolutionized Oncology and Immunological diseases. It is moving towards cell and gene therapies where the technology is proving itself in ultrarare diseases, and much like their predecessor technologies, will move toward more broad-based applications over time.

2022 will continue to see the explosive advancement of gene therapy and gene editing technologies that results in new companies and investments across the industry. As these technologies advance through the clinic in the years to come, we will see them applied more broadly to address genetic diseases that affect broader patient populations. We are already seeing the move from muscular dystrophy to sickle cell disease and beyond. From Locus, you will see our team take our CRISPR-Cas3 enhanced bacteriophage into a Phase 2 trial targeting urinary tract infections caused by E. coli a disease that affects millions of people each year in the US alone.

Triangle gene editing firm Locus lands $77M to support new antibacterial treatment

TW: What can you tell us about how the companys geographic location in the Triangle means for future opportunity?

The Locus manufacturing platform is the lynchpin of our success in progressing bacteriophage products by enabling internal control over the timing, quality and speed at which we can take drugs to the clinic. We leverage our teams deep manufacturing experience as well as our geography, as NC is an ideal manufacturing location due to the local economics and talent pool.

Our world-class 10,000 square foott modular cGMP biologics manufacturing facility meets the standards of the US (FDA), Europe (EMA), Japan (PMDA), and several other countries and regions, to enable the manufacture of our precision medicines while providing the capability to also manufacture gene therapy vectors and other advanced biologics. Our facility design allows for parallel production of multiple drug substances simultaneously, in isolated production suites, without risk of cross-contamination. It is optimized for viral vector manufacturing, including bacteriophage, adenovirus, AAV, and other vectors. Taken together, our facility and proprietary production processes allow for all viral products manufactured by Locus to meet or exceed US and international regulatory standards for parenterally administered drug products for clinical and commercial use.

The modular design also allows us to change-out or upgrade existing equipment that moves Locus from being able to produce clinical trial material to producing multiple early-stage commercial products in parallel; all while maintaining the same footprint.

Locus Biosciences lands $19M in funding for gene editing technology

Read more:

Triangle gene editing firms CEO: There is a revolution occurring in medicine - WRAL TechWire

The This research service discusses the cell and gene therapy (CGT) market and highlights some key roadblocks in viral vector manufacturing. While many CGT candidates exist in the pipeline, there is a huge capacity deficit that the industry is collaboratively trying to address.

New York, Dec. 21, 2021 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "Technology Developments in Viral Vector Manufacturing for Cell and Gene Therapies" - https://www.reportlinker.com/p06192548/?utm_source=GNW

Scalability, costs, reproducibility, and overall process efficiency are some of the main pain points at each step of the viral vector manufacturing process.Many industry stakeholders are capitalizing on innovative, sustainable business models and capacity expansion investments to address shortage issues.

Biotechnology companies, such as Merck, Novartis, and Pfizer, and key contract development and manufacturing organizations, such as Thermo Fisher Scientific, Catalent, and FUJIFILM Diosynth Technologies, are investing in new capacities, expanding capacities, and developing innovative technologies to stay ahead in the CGT market. The research covers emerging technologies and trends, challenges, and opportunities across the manufacturing workflow, from upstream (viral vector production) to downstream (viral vector purification). Key developments in upstream processes for viral vector production include advanced transfection agents, novel plasmids, suspension-adapted cell culture, and stable producer cell lines. The research also discusses the general industry shift toward adopting automation, digitization, and advanced analytical processes, including on-line and in-line analytics and robust real-time analytics, to highlight the importance of analytical tools throughout the value chain. Smart technologies, such as automation and digital tools, and the adoption of artificial intelligence and big data support progress in process control and optimization while improving overall efficiencies and safety. The CGT industry works through orchestrated collaborations to develop reference standards and build process analytical technologies (PAT) to optimize manufacturing further. The research presents a birds eye view of key stakeholders and their innovative platforms and a snapshot of the collaborative ecosystem to understand the CGT industrys dynamic and fast-paced nature.Read the full report: https://www.reportlinker.com/p06192548/?utm_source=GNW

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

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Technology Developments in Viral Vector Manufacturing for Cell and Gene Therapies - Yahoo Finance

DUBLIN--(BUSINESS WIRE)--The "Global Regenerative Medicine Market Size, Share & Trends Analysis Report by Product (Cell-based Immunotherapies, Gene Therapies), by Therapeutic Category (Cardiovascular, Oncology), and Segment Forecasts, 2021-2027" report has been added to ResearchAndMarkets.com's offering.

The global regenerative medicine market size is expected to reach USD 57.08 billion by 2027, growing at a CAGR of 11.27% over the forecast period.

Recent advancements in biological therapies have resulted in a gradual shift in preference toward personalized medicinal strategies over the conventional treatment approach. This has resulted in rising R&D activities in the regenerative medicine arena for the development of novel regenerative therapies.

Furthermore, advancements in cell biology, genomics research, and gene-editing technology are anticipated to fuel the growth of the industry. Stem cell-based regenerative therapies are in clinical trials, which may help restore damaged specialized cells in many serious and fatal diseases, such as cancer, Alzheimer's, neurodegenerative diseases, and spinal cord injuries.

For instance, various research institutes have adopted Human Embryonic Stem Cells (hESCs) to develop a treatment for Age-related Macular Degeneration (AMD).

Constant advancements in molecular medicines have led to the development of gene-based therapy, which utilizes targeted delivery of DNA as a medicine to fight against various disorders.

Gene therapy developments are high in oncology due to the rising prevalence and genetically driven pathophysiology of cancer. The steady commercial success of gene therapies is expected to accelerate the growth of the global market over the forecast period.

Regenerative Medicine Market Report Highlights

Key Topics Covered:

Market Variables, Trends, & Scope

Competitive Analysis

Covid-19 Impact Analysis

Regenerative Medicine Market: Product Business Analysis

Regenerative Medicine Market: Therapeutic Category Business Analysis

Regenerative Medicine Market: Regional Business Analysis

Companies Mentioned

For more information about this report visit https://www.researchandmarkets.com/r/kovhgl

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Global Regenerative Medicine Market is Expected to Reach USD 57.08 Billion by 2027, Growing at a CAGR of 11.27% Over the Forecast Period. -...

COVID-19 spread and vaccines

NIH researchers continued to make scientific breakthroughs to help control the COVID-19 pandemic. Studies of spread suggested strategies for controlling infections. Research also revealed who was most at risk of becoming severely ill from COVID-19: nearly two-thirds of COVID-19 hospitalizations in the U.S. were due to obesity, diabetes, hypertension, and heart failure. Wide-spread vaccine rollouts slowed the spread of SARS-CoV-2, the virus that causes COVID-19. The Moderna COVID-19 vaccine, developed with NIH, proved to be 94% effective against symptomatic COVID-19. Six months later, people who had been vaccinated still showed signs of immunity. COVID-19 vaccines saved an estimated 140,000 lives through May 2021, and hundreds of thousands more have been saved since. As SARS-CoV-2 mutated and new variants became common, scientists conducted studies on booster doses of vaccine. These suggested that COVID-19 boosters not only lengthen immunity but help broaden and strengthen the immune response to protect against a wide variety of variants.

In type 1 diabetes, the immune systems T cells attack the insulin-producing beta cells in the pancreas. Those affected need insulin treatment to survive. In a clinical trial of people at risk of developing type 1 diabetes (with a median age of 13), the drug teplizumab delayed disease onset and improved insulin production. The findings support the use of the drug for delaying or preventing type 1 diabetes.

There has been a great deal of debate over what aspects of our diets affect weight control. A carefully controlled study found that people ate fewer calories per day and lost more weight on a plant-based, low-fat diet compared to an animal-based, low-carb diet. However, the low-fat diet led to higher insulin and blood sugar levels, which can be risk factors for heart disease. The findings reveal how restricting dietary carbohydrates or fats may impact health.

The effects of childhood malnutrition can cause lifelong health problems. Researchers found that a supplement designed to repair the gut microbiomethe bacteria, viruses, and fungi in the digestive systemhelped malnourished children. Those given the supplement gained more weight than children on a standard nutritional supplement. The experimental supplement also raised levels of proteins in the blood associated with bone, cartilage, and brain health.

A common blood test for kidney function measures a protein called creatinine. But Black Americans generally have higher amounts of creatinine. As a result, doctors take race into account when testing for kidney disease. A study showed that measuring levels of another protein called cystatin C can accurately estimate kidney function without needing to take race into account. A race-blind method for estimating kidney function could more effectively identify chronic kidney disease.

Malaria is caused by parasites transmitted by infected mosquitoes. Researchers developed a vaccine approach that uses live sporozoites, the infectious form of the malaria parasite, along with a drug that kills the parasite. In a small trial, the approach led to broad, long-lastingprotection against malaria. The strategy is now being tested in real-world conditions in a Phase 2 clinical trial in Mali.

See the article here:

2021 Research Highlights Human Health Advances - National Institutes of Health

We live in capitalist economies that deliver great wealth, innovation and dynamism but lurch from systemic crisis to crisis, throw up gigantic inequalities and are careless about nature and the societies of which they are part. Its obvious that we want more of the former and less of the latter but how? Never easy, this question is now so bitterly dividing western politics that in the US there is even talk of a second civil war. Post-Brexit Britain is only fractionally less toxic.

There are two increasingly hostile camps living in their intellectual and political silos. On the one hand, there are the me firsts, the apostles of salvation through individualism. Capitalism propelled by individuals aggressively pursuing their own self-interest will deliver the goods. It is essentially self-organising, self-propelling and self-dynamic. Dont worry about booms, busts, monopoly and disastrous social side-effects; we have to put up with them as we do with the weather. They will sort themselves out in time. Any public intervention will bring errors and costs that outweigh the benefits. Allow the tall poppies to grow even taller and wealth will ultimately trickle down; inequality is the price paid for capitalist effectiveness. Capitalism harnesses the base metals of human greed and self-interest to deliver the alchemy of economic dynamism.

On the other hand, are the we firsts. They are equally passionate in their insistence that salvation lies in the group and society and convinced, whether on the climate emergency, hi-tech monopolies, crippling uncertainties about living standards or just the evident truth that we humans are altruists as much as individualists, that to follow the me firsts is the road to perdition. What is crucial to us as social beings is the group, society, the commonweal and belonging as equals. After all, it was associating in groups that was fundamental to our evolutionary capacity to hunt and to see off predators. That primeval urge to associate in the group is what underpins happiness and wellbeing. What people want is less the exercise of choice in markets, more to control their lives in the service of what they value and that is best done collectively and, as far as possible, equitably.

And so the Is and wes confront each other in intense enmity, crystallised in the debates about the proper reaction to the virus. The Is inhabit a world in which we must make our own choices, even over vaccination, and the state must be minimalist. The wes urge mandatory vaccination, early lockdowns and Covid passports. Yet the sustainable policy is to blend the two: to find ways of persuading individuals, by choice and shaming, to get vaccinated and to ensure that Covid passports are employed, but only when it is clear that public health demands it for NHS and care workers and for any large events. Too much we zeal and there is insupportable state intrusion into our lives; too much I libertarianism and you are free to infect and maybe kill me. Yes, we need the pluralism of different options and individual agency; equally, we need an agile public realm and collective action to serve the group.

The good society (and successful public policy) is one that cleverly uses its institutions to reconcile the we with the I. It is great institutions, in the private and public sectors, which bind society and mitigate the worst excesses of both group force and individual licence. The problem is that we have too few of them and those we do have are being undermined by the dominance of the me firsts who insist anything to do with the we is coercive and undermines liberty.

Thus, despite the me firsts, we witness the success of the NHS through this pandemic, plainly dedicated to serve the we but never in such a way as to be oppressive. Thus, too, the amazing vaccines incubated in Oxfords Jenner Institute, the university itself an example of combining the we of a shared academic vocation but with 37 individual, competing colleges. These were then rolled out with the impetus of the Cell and Gene Therapy Catapult, an institution part tax-funded and part funded from its own commercial activities but one consecrated to promoting the public interest of a strong cell and gene ecology. And all further enabled by an enlightened capitalist enterprise, AstraZeneca, which institutionally recognised its social purpose of promoting health by selling a billion doses at cost.

Another institution that has proved its worth in the pandemic is the BBC, particularly its political and health teams. Laura Kuenssberg and Ros Atkins, for example, have shown the power of impartiality, while Fergus Walsh and Hugh Pym have been models of rock-solid, informed reporting. It has had a cascade effect on much of the media. In a deadly pandemic, beyond some on the Conservative backbenches and rightwing columnists, there can be no luxuriating in ideology. Everyone wants to get to the other side in the best and safest way they can.

Our democratic institutions have been less secure. The checks and balances vital to political integrity have been found wanting. It should never have been possible for the prime minister to use executive discretion, backed by a parliamentary majority, retrospectively to change the terms of the committee on standards in public life; it should be understood that these institutions, including the Electoral Commission, can be reformed only deliberatively and with cross-party support. They represent the we. Public procurement, too, has proved spectacularlyopen to abuse. Meanwhile, the Tory party has demonstrated its institutional weakness, becoming hostage to its ultra-libertarian wing and arriving at public health policies erratically and often too late.

The wider lesson is clear. If we want the best of capitalism and less of the worst, we need to build institutions across our economy, society and democracy that covenant through their constitutions, from a company to a university, that they will respect values we hold dear: equality, fairness, universality, transparency, societal obligation and sustainability. Indeed, in the face of 21st-century challenges AI, the drive to net zero, levelling up great institutions are more important than ever. They will not emerge spontaneously from markets and the operation of capitalism. They have to be created and sustained, the progressive project of the decades ahead.

Will Hutton is an Observer columnist. His December lecture to the Academy of Social Sciences, Its institutions stupid the moralisation of capitalism, from which this column is drawn, is available here

Read more:

Which philosophy helps us confront the crises that beset us... we first or me first? - The Guardian

Seven people who underwent heart-bypass surgery recently in Europe volunteered to receive an additional treatment: injections of messenger RNA.

This was not one of the COVID-19 vaccines, in which the RNA code is used to teach the recipients immune system. Instead, the RNA for the surgery patients was designed to heal their hearts by promoting the growth of new blood vessels.

The study, a collaboration between drugmakers AstraZeneca and Moderna, is among dozens underway to harness the potential of RNA. Some of them started before the pandemic, but with the real-world success of the vaccines, they have now picked up steam.

At Duke University Medical Center, researchers are testing a different RNA-based drug from Moderna in patients with propionic acidemia, a rare disorder in which the liver is unable to break down certain amino acids and fats. Others are testing messenger RNA against a variety of cancers.

And, of course, RNA is being used to make more vaccines. Among those being tested are vaccines against Zika virus, respiratory syncytial virus (RSV), cytomegalovirus, and the flu.

All these efforts rely on RNAs ability to carry the recipe for proteins, the building blocks of life. In a vaccine, the protein is a harmless fragment of the virus in question, allowing the recipients immune system to practice in the event of infection. In the other drugs, the RNA can prompt patients cells to make beneficial proteins that they are unable to make themselves.

It is too soon to say how well the various non-vaccine RNA drugs will work, said cardiologist Howard J. Eisen, a medical director at the Penn State Heart and Vascular Institute, who has been following the research. Among other issues: RNA degrades quickly (remember how the COVID vaccines require cold storage?), so it has to be delivered to the right cells in a timely fashion.

Yet the potential, he says, is vast.

Itll revolutionize medicine, I think.

In the heart study, patients experienced no serious side effects as a result of the injections, the drugmakers reported in November. That was little surprise, given that billions have now been injected safely with RNA vaccines, said Eisen, who was not involved with the study.

But with just seven people (and another four who received placebo injections), the study was too small to draw conclusions about the drugs effect on heart function. Larger studies are planned.

The RNA carries the recipe for a protein called VEGF-A, a growth factor involved in forming new blood vessels. The hope is that the patients would experience an improved ejection fraction a measure of how much oxygenated blood is pumped with each heartbeat. Yet previous studies, in which researchers have sought to boost that protein with a different approach called gene therapy, have met with limited success.

Likewise, tests of the RNA-based drug for propionic acidemia are in the early stages, as are studies of RNA treatments for other metabolic diseases.

Whats clear is that new approaches for these liver disorders are sorely needed, said Dwight Koeberl, who is overseeing the Duke University site for Modernas propionic acidemia trial.

For now, patients with that disease must severely limit or avoid intake of meat, dairy, and nuts or else their bodies build up toxic byproducts that lead to neurological and heart damage, among other complications. To compensate for this restricted diet, they must drink a special formula with vitamins and other supplements. And even so, some eventually need a liver transplant.

Koeberl, a professor of pediatrics at Duke University School of Medicine, also has studied the use of gene therapy to treat such patients. That approach is a long-term fix, as the instructions for making the corrective proteins are delivered inside the nucleus of the persons cells (whereas RNA is transient, degrading within days meaning that some treatments would need to be administered multiple times).

But as with the gene therapy treatments for heart disease, gene therapy for metabolic disorders remains a work in progress. One hurdle with gene therapy is that it is typically delivered inside the recipients cells with a virus, which can be defeated by the immune system, Koeberl said.

RNA-based therapies, on the other hand, are typically packaged in tiny droplets of oily molecules called lipids, as with the COVID vaccines. These lipid nanoparticles do not enter the cell nucleus. They need to penetrate only the outer cell membrane for the RNA to fulfill its mission, and they do so with ease. Koeberl was attracted by the possibility of a more straightforward solution.

My interest is in trying to help these patients with something sooner rather than later, he said.

Many, if not most, of the RNA drugs being tested are vaccines, to judge from a search of clinicaltrials.gov, a listing of clinical studies maintained by the U.S. National Library of Medicine.

Compared to traditional vaccines, one advantage of the RNA approach is that the genetic instructions can be quickly updated to match emerging threats. Pfizer and BioNTech, for example, already are developing a vaccine to match the omicron variant of the coronavirus, though widescale production still takes time. The European Union has ordered 180 million doses of this modified vaccine, expected to be available by March.

Next-generation RNA vaccines may also have the advantage of requiring lower doses. Thats the idea behind a flu vaccine in development by Seqirus, which has U.S. operations in Summit, N.J., and is a subsidiary of CSL Limited, based in Melbourne, Australia.

The RNA in that vaccine is self-amplifying, meaning that it consists of two elements: the genetic recipe for making flu proteins that stimulate an immune response, as well as instructions to make multiple copies of that recipe. In theory, that would mean a lower dose of such a vaccine could be just as effective, yet with a lower rate of side effects. Seqirus has been studying this approach in animal models for years, and it plans to test this type of flu vaccine in human volunteers during the second half of 2022.

Patient support groups have been watching the development of messenger RNA with great interest, whether the drug is being used to prevent disease, as with the vaccines, or to treat it.

Many advocates were aware of the potential for RNA treatments long before the COVID vaccines came out. Among them is Kathy Stagni, executive director of the Organic Acidemia Association, which provides support for patients with propionic acidemia and others.

She said she has been setting the record straight every time she hears someone claim that the technology behind the COVID vaccines was rushed.

This is something theyve been working on for a long time, she said.

Eisen, the Penn State cardiologist, was working at the University of Pennsylvania decades ago when Penn scientist Katalin Karik was doing some of the early experiments that would set the stage for the vaccines.

She was not working on vaccines at the time, but on using messenger RNA to treat heart disease. Now that the technology has matured, AstraZeneca and Moderna are tackling heart disease once again.

In essence, Eisen said, it has come full circle.

More here:

Vaccines are just the beginning for RNA. The technology is being tested on heart and liver diseases. - The Philadelphia Inquirer

What a year. We laughed, we cried, we socially distanced and we held our loved ones close. And ... we read the news. A lot of it.

As part of our look back at 2021, we've pulled together a collection of some of the stories that USA TODAY readers spent the most time with this year.

The selections includea profile of the New Jersey man who became the world's first successful face and double-hand transplant recipient, the journey of a little girl with a rare disease who was given hope through a medical miracle and thestory of onefamily's drug ring that was linked to the Sinaloa Cartel and deaths in three states.

There are also stories of redemption, remembrance and faith, including a woman's tale of escaping Afghanistan and the story of a young boy who lost his mom on 9/11 and the young man he's become.

All of these pieces were available to USA TODAY subscribers this year and we're making them free this holiday season.

If you want unlimited access tounique, straightforwardreporting from around the nation that takes you beyond the headlines, please consider a subscription to USA TODAY.

Stories of the Year: A look back at the biggest moments of 2021

Photos of the Year: See a photo from every day in a life-changing year

Those We Lost: Hank Aaron, Bob Dole, Cicely Tyson: Remembering notables who died in 2021

Feel-good stories: From daring rescues to medical breakthroughs, here are 12 of the happiest stories of 2021

A Sinaloa Cartel supplied drug ring is tied to multiple deaths in Michigan, Kentucky and Mississippi, a USA TODAY Network investigation finds.

After a car accident destroyed his face and arms, Joseph DiMeo determined to recover his independence. Now, after complex transplant surgery, he has.

For decades, two lovestruck teenagers made good on a promise to their parents to never talk again. But one day, 51 years later, everything changed.

Five years after then-coach Tyler Summitt was caught having an affair with his point guard at Louisiana Tech, the couple are married and have a son.

When NCAA men's basketball referee Bert Smith collapsed during the Gonzaga-USC game, some thought he had died. Turns out, that fall saved his life.

A scientific vision for decades, gene therapy is finally becoming more common in the U.S., fueling optimism for the treatment of rare diseases.

In 2001, Tionda and Diamond Bradley left a note and disappeared from their Chicago home. For two decades, their family has fought for answers.

The boy in the yellow raincoat made for one of 9/11's most moving images. Two decades after the attacks, Kevin Villa reflects on his mom's sacrifice.

It seems impossible that civilization can regress decades, that your life can collapse before lunch. But it can, and it did as the Taliban took Kabul.

Bishop Sycamore gained national attention when it lost an ESPN-televised football game 58-0 and questions were asked about the school and coaches.

Published1:01 pm UTC Dec. 25, 2021Updated2:17 pm UTC Dec. 25, 2021

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Long reads: The USA TODAY stories readers spent the most time with in 2021 - USA TODAY

Cavazzano-Calvo, M. (2010). Transfusion independence and HMGA2 activation after gene therapy of human beta-thalassaemia. Nature 467, 318-322. doi:10.1038/nature09328

Cideciyan, A.V. et al (22 January 2013). Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement. Proceedings of the National Academy of Sciences of the United States of America, Earline Online Publication. doi: 10.1073/pnas.1218933110

MacLaren, R.E. et al (16 January 2014). Retinal gene therapy in patients with choroideremia: initial findings from a phase 1/2 clinical trial. The Lancet, Early Online Publication. doi:10.1016/S0140-6736(13)62117-0

Nathwani, A.C. (2011). Adenovirus-associated virus vector-mediated gene transfer in hemophilia B. The New England Journal of Medicine, 365(25), 2357-2365.

Nienhuis, A.W. (2013). Development of gene therapy for blood disorders: an update. Blood 122(9), 1556-1564. doi: 10.1182/blood-2013-04-453209

Palfi, S. et al (10 January 2014). Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for parkinson's disease; a dose escalation, open-label, phase 1/2 trial. The Lancet, Early Online Publication. doi: 10.1016/S014006736(13)61939-X

Penn Medicine (7 December 2013). Penn medicine team reports findings from research study of first 59 adult and pediatric leukemia patients who received investigational, personalized cellular therapy CTL019. Retrieved from http://www.uphs.upenn.edu/news/News_Releases/2013/12/ctl019/

Persons, Derek A. (2010). Gene therapy: Targeting beta-thalassaemia. Nature 467, 277-278. doi: 10.1038/467277a

Petrs-Silva, H. & R. Linden (2014). Advances in gene therapy technologies to treat retinitis pigmentosa. Clinical Opthalmology 2014(8), 127-136. doi: 10.2147/OPTH.538041

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Gene Therapy Successes - University of Utah

Over the years genetic disorders and gene-related illness have been responsible for high mortality rates and reduced quality of life. Some of the congenital abnormalities manifest quite early, and there are minimal hopes for survival in these children, this causes much pain to their families because management option is limited and there is very little at their disposal to modify such conditions. Scientists are developing a relatively new technique that will give hope to the hopeless and make life better. Genetic disorders can be due to misalignment, missing genes or excess of a gene. Genetic therapy works at the elementary level of heredity to replace the defective genes with new ones.

Gene therapy is the insertion of new functional genes into an individuals cell or tissue to replace the defective one and modify a hereditary disease. This is a new research area, and much research projects are still in the infancy or trial stages; however, expectations are high, and we would potentially do away with genetic diseases soon enough. Developed in 1972, gene therapy can be of two type; somatic gene therapy and germline gene therapy. It is especially promising in treating genetic disorders such as muscular dystrophy and cystic fibrosis. Critics have their say and look at the two sides of the story will lead us to weigh risk: benefit ration. Gene therapy pros and cons can be quite decisive on whether or not we should embrace gene therapy.

Research into gene therapy has been ongoing for decades now, and there is light at the end of the tunnel as gene therapy is associated with the following advantages;

Genetic defect occur even after thorough screening and many people have their lives compromised or limited by such disorders. In the United States alone as at 2009, 3% congenital disabilities were recorded in all births, the joy of having a child is suddenly lost and replaced with the agony and struggle of maintaining such demanding life. Individual patient and family are pessimistic as efforts to change the condition by traversing through different levels of healthcare are always thwarted since no cure exists for such situations. Gene therapy intent to correct such birth defects responsible for more than half of infant mortality is laudable. We can be confident that all the unborn babies will be delivered safely and grow to their prime. Besides, gene therapy promises a cure for the chronic illnesses that are currently incurable for example cancer that causes agonizing pain in many.

By replacing a defective gene with a functional gene in a disease like cystic fibrosis, there are limited chances of remission, and this is usually a one-off treatment that will see you symptom-free for life. Furthermore, gene therapy is not just a remedy to the individual suffering from a given condition, but it covers the entire generation. When you remove a gene predisposing one to breast cancer they wont transfer the defective genes to their offspring but the new functional gene.

Some of the initially incurable diseases can be managed and possibly eliminated when we involve gene therapy. Alterations to gene especially the reproductive genes using the germline method can help in avoiding transmission of defective genes and thus no further incidences of disease. Parkinsons disease, Huntingtons disease, and Alzheimers disease are but a few conditions that are likely to be eliminated by gene therapy.

Not only does gene therapy focus on diseases. Conditions that may make life unlimited such as infertility are also accounted for, and it is projected that soon enough gene therapy should activate reproductive genes and allow you to have children.

Gene therapy promises much potential in the medical field ranging from relieving the pill burden to modifying phenotypes in cosmetology.

Although gene therapy has a potential for treating several ailments and improving life, this is a relatively new technique and involve several safety concerns thus it should be carefully embraced. Some of the notable disadvantages of gene therapy include;

As at now, gene therapy is at the developmental stages, and most experiments are done on the animals with the hope that success will be reflected in humans. However, anything can happen, and gene therapy can fail to work thus limit your capabilities or even worsen the condition. Incompatibility issues and immune response can also lead to failure of the procedure. The massive ongoing research will leverage the concerns and provide a technological-based method with a high certainty of results.

The cost of performing gene therapy is likely to be high because it involves sophisticated equipment and high-level expertise. Such a fee may not be affordable to many, and this will create socioeconomic segregation as the rich will be disease-free while the poor remain to bear the burden of such illness. A solution to this would possibly be extensively integrating technology in the process since technologically based therapy may prove more cost-effective even when compared to the other therapeutic options.

Superb as it may look, gene therapy may be short-lived. Nature is unpredictable, and sometimes it may take its course for the worse. Just like the antibiotics were novel at the time of invention, it is possible that the use of gene therapy may gain resistance as well. There is no guarantee that gene therapy will fulfill its expectations to treat explicit disorders, performing gene adjustments could create new defects for future generations without realizing it; thus it can be a double-edged sword.

One of the greatest hindrance to the advancement of gene therapy is the opposition on the basis that it can open room for unethical science which may be demeaning to the human race. The thoughts that gene therapy creates a perfected human has been very controversial.

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Gene Therapy Pros and Cons - Biolyse

In the summer of 2015, a 7-year-old named Hassan was admitted to the burn unit of the Ruhr University Childrens Hospital in Bochum, Germany, with red, oozing wounds from head to toe.

It wasnt a fire that took his skin. It was a bacterial infection, resulting from an incurable genetic disorder. Called junctional epidermolysis bullosa, the condition deprives the skin of a protein needed to hold its layers together and leads to large, painful lesions. For kids, its often fatal. And indeed, Hassans doctors told his parents, Syrian refugees who had fled to Germany, the young boy was dying.

The doctors tried one last thing to save him. They cut out a tiny, unblistered patch of skin from the childs groin and sent it to the laboratory of Michele de Luca, an Italian stem cell expert who heads the Center for Regenerative Medicine at the University of Modena and Reggio Emilia. De Lucas team used a viral vector to ferry into Hassans skin cells a functional version of the gene LAMB3, which codes for laminin, the protein that anchors the surface of the skin to the layers below.

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Then the scientists grew the modified cells into sheets big enough for Ruhr University plastic surgeons Tobias Hirsch and Maximilian Kueckelhaus to graft onto Hassans raw, bedridden body, which they did over the course of that October, November, and the following January.

It worked better than the boys doctors could have imagined. In 2017, de Luca, Hirsch, Kueckelhaus, and their colleagues reported that Hassan was doing well, living like a normal boy in his lab-grown skin. At the time though, there was still a big question on all their minds: How long would it last? Would the transgenic stem cells keep replenishing the skin or would they sputter out? Or worse could they trigger a cascade of cancer-causing reactions?

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Today, the same team is out with an update. Five years and five months after the initial intervention, Hassan is still, for the most part, thriving in fully functional skin that has grown with the now-teenager. He is attending school, and playing sports with his friends and siblings, though he avoids swimming due to blistering in the areas that werent replaced by the lab-grown skin. One of his favorite activities is a pedal-powered go kart. There are no signs his modified stem cells have lost their steam, and no traces of tumors to be found.

The encouraging follow-up data has been instrumental in moving forward a larger clinical trial of the approach, offering hope to the 500,000 epidermolysis bullosa patients worldwide currently living without treatment options.

We were astonished by the speedy recovery, Kueckelhaus, now at University Hospital Muenster, told STAT via email. But experience from skin transplantation in other settings made him and his colleagues wary of the grafts failing as the months and years wore on. Thankfully, wrote Kueckelhaus, those fears never materialized. We are very happy to be able to prove that none of these complications appeared and the genetically modified skin remains 100% stable. The chances are good that he will be able to live a relatively normal life.

Over the last five years, Hassans team of doctors and researchers has put his new skin through a battery of tests checking it for sensitivity to hot and cold, water retention, pigmentation and hemoglobin levels, and if it had developed all the structures youd expect healthy skin to have, including sweat glands and hair follicles. Across the board, the engineered skin appeared normal, without the need for moisturizers or medical ointments. The only flaw they found was that Hassans skin wasnt as sensitive to fine touch, especially in his lower right leg. This mild neuropathy they attributed not to the graft itself, but to how that limb was prepared doctors used a more aggressive technique that might have damaged the nerves there.

The team also used molecular techniques to trace the cells theyd grown in the lab as they divided and expanded over Hassans body. They found that all the different kinds of cells composing the boys new skin were being generated by a small pool of self-renewing stem cells called holoclone-forming cells, carrying the Italian teams genetic correction.

This was quite an insight into the biology of the epidermis, said de Luca. Its an insight he expects will have huge consequences for any efforts to advance similar gene therapies for treating other diseases affecting the skin. You have to have the holoclone-forming cells in your culture if you want to have long-lasting epidermis, he said.

The approach pioneered by de Lucas team will soon be headed for its biggest clinical test yet, after nearly a decade of fits and starts. They expect to begin recruiting for a multi-center Phase 2/3 trial sometime next year.

De Luca first successfully treated a junctional EB patient in 2005. But then a change to European Union laws governing cell and gene therapies forced his team to stop work while they found ways to comply with the new rules. It took years of paperwork, building a manufacturing facility, and spinning out a small biotech company called Holostem to be ready to begin clinical research again. Hassan came along right as they were gearing up for a Phase 1 trial, but data from the boys case, which was granted approval under a compassionate use provision, convinced regulators that the cell grafts could move to larger, more pivotal trials, according to de Luca.

We didnt cure the disease, he told STAT. But the skin has been restored, basically permanently. We did not observe a single blister in five years. The wound healing is normal, the skin is robust. From this point of view, the quality of life is not even comparable to what it was before.

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Syrian refugee is thriving five years after last-gasp gene therapy - STAT - STAT

Gene therapy is a powerful developing technology that has the potential to address myriad diseases. For example, Huntington's disease, a neurodegenerative disorder, is caused by a mutation in a single gene, and if researchers could go into specific cells and correct that defect, theoretically those cells could regain normal function.

A major challenge, however, has been creating the right "delivery vehicles" that can carry genes and molecules into the cells that need treatment, while avoiding the cells that do not.

Now, a team led by Caltech researchers has developed a gene-delivery system that can specifically target brain cells while avoiding the liver. This is important because a gene therapy intended to treat a disorder in the brain, for example, could also have the side effect of creating a toxic immune response in the liver, hence the desire to find delivery vehicles that only go to their intended target. The findings were shown in both mouse and marmoset models, an important step towards translating the technology into humans.

A paper describing the new findings appears in the journal Nature Neuroscience on December 9. The research was led by Viviana Gradinaru (BS '05), professor of neuroscience and biological engineering, and director of the Center for Molecular and Cellular Neuroscience.

The key to this technology is the use of adeno-associated viruses, or AAVs, which have long been considered promising candidates for use as delivery vehicles. Over millions of years of evolution, viruses have evolved efficient ways to gain access into human cells, and for decades researchers have been developing methods to harness viruses' Trojan-Horse-like abilities for human benefit.

AAVs are made up of two major components: an outer shell, called a capsid, that is built from proteins; and the genetic material encased inside the capsid. To use recombinant AAVs for gene therapy, researchers remove the virus's genetic material from the capsid and replace it with the desired cargo, such as a particular gene or coding information for small therapeutic molecules.

"Recombinant AAVs are stripped of the ability to replicate, which leaves a powerful tool that is biologically designed to gain entrance into cells," says graduate student David Goertsen, a co-first author on the paper. "We can harness that natural biology to derive specialized tools for neuroscience research and gene therapy."

The shape and composition of the capsid is a critical part of how the AAV enters into a cell. Researchers in the Gradinaru lab have been working for almost a decade on engineering AAV capsids that cross the blood-brain barrier (BBB) and to develop methods to select for and against certain traits, resulting in viral vectors more specific to certain cell types within the brain.

In the new study, the team developed BBB-crossing capsids, with one in particular AAV.CAP-B10that is efficient at getting into brain cells, specifically neurons, while avoiding many systemic targets, including liver cells. Importantly, both neuronal specificity and decreased liver targeting was shown to occur not just in mice, a common research animal, but also in laboratory marmosets.

"With these new capsids, the research community can now test multiple gene therapy strategies in rodents and marmosets and build up evidence necessary to take such strategies to the clinic," says Gradinaru. "The neuronal tropism and decreased liver targeting we were able to engineer AAV capsids for are important features that could lead to safer and more effective treatment options for brain disorders."

The development of an AAV capsid variant that works well in non-human primates is a major step towards the translation of the technology for use in humans, as previous variants of AAV capsids have been unsuccessful in non-human primates. The Gradinaru lab's systematic in vivo approach, which uses a process called directed evolution to modify AAV capsids at multiple sites has been successful in producing variants that can cross the BBBs of different strains of mice and, as shown in this study, in marmosets.

"Results from this research show that introducing diversity at multiple locations on the AAV capsid surface can increase transgene expression efficiency and neuronal specificity," says Gradinaru. "The power of AAV engineering to confer novel tropisms and tissue specificity, as we show for the brain versus the liver, has broadened potential research and pre-clinical applications that could enable new therapeutic approaches for diseases of the brain."

The paper is titled "AAV capsid variants with brain-wide transgene expression and decreased liver targeting after intravenous delivery in mouse and marmoset." Goertsen; Nicholas Flytzanis (PhD '18), the former scientific director of the CLARITY, Optogenetics and Vector Engineering Research(CLOVER)Center of Caltech's Beckman Institute; and former Caltech postdoctoral scholar Nick Goeden are co-first authors. Additional coauthors are graduate student Miguel Chuapoco, and collaborators Alexander Cummins, Yijing Chen, Yingying Fan, Qiangge Zhang, Jitendra Sharma, Yangyang Duan, Liping Wang, Guoping Feng, Yu Chen, Nancy Ip, and James Pickel.

Funding was provided by the Defense Advanced Research Projects Agency, the National Institutes of Health, and the National Sciences and Engineering Research Council of Canada.

Flytzanis, Goeden, and Gradinaru are co-founders of Capsida Biotherapeutics, a Caltech-led startup company formed to develop AAV research into therapeutics.

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New Technology is One Step Closer to Targeted Gene Therapy - Caltech

By Anthony O. Goriainoff

N4 Pharma PLC said Monday that it will focus its resources on advancing its work on gene therapy, and that it will continue its vaccine-delivery efforts in conjunction with partners and working on specific proprietary products.

The AIM-listed pharmaceutical company said the preliminary results from mouse immunogenicity studies carried out by Evotec SE using Covid-19 didn't show meaningful immunological response, and that this brought into question the whole study. The company said it will concentrate future vaccine work through its material transfer agreements [MTA] and that it was in advanced discussions with another company focusing on mRNA delivery with a view to scoping the work to be undertaken under a new MTA.

The company said that although the results on the vaccine work from Evotec were unexpected, the proof-of-concept data collated to date has been sufficient to allow it to sign MTAs with potential vaccine collaborators.

"We expect other collaborations will follow, so it makes sense to continue the vaccine platform optimization with collaborators who own their own DNA plasmids and mRNA compounds. This will allow us to focus internal efforts on developing commercial products in the gene therapy space," Chief Executive Nigel Theobald said.

Write to Anthony O. Goriainoff at anthony.orunagoriainoff@dowjones.com

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N4 Pharma to Focus Resources on Advancing Gene Therapy Work - MarketWatch

The Cystic Fibrosis Foundationis funding three new early-stage research awards worth more than $1.8 million to bolster the development of potential gene therapies for cystic fibrosis (CF).

This funding will support critical early steps necessary for the development of genetic therapies for cystic fibrosis, William Skach, MD, executive vice-president and chief scientific officer of the CF Foundation, said in a press release. These promising programs are tackling difficult challenges such as efficient therapeutic delivery of diverse genetic cargos and evasion or modulation of the immune systems response to gene delivery vehicles.

Gene therapy works by adding a new gene or replacing or repairing a mutated gene inside cells in the body. To get gene therapy into the cells, it first must be packed into a carrier, usually a harmless virus. However, other carriers exist that may deliver gene therapy.

Carmine Therapeutics was awarded more than $766,000 to test one such alternative type of carrier. The company plans to use tiny particles, called vesicles, that naturally bud off from red blood cells to deliver a healthy copy of cystic fibrosis transmembrane conductance regulator (CFTR) the gene mutated in people with CF into lung cells. Unlike other carriers, which sometimes trigger an immune response, the vesicles are expected to be well-tolerated by the immune system, even upon repeat administration.

If a viral carrier must be used, the bodys immune response should be blocked to allow repeat administration. GenexGen was awarded close to $595,000 to develop a way to lessen the immune response to a viral carrier. The company is testing an approach that uses CRISPR a kind of molecular scissors that can cut pieces of DNA to target a certain gene that plays a key role in the immune system. The goal is to turn off that gene temporarily, thus allowing gene therapy to be delivered by a virus.

Finally, Specific Biologics was awarded more than $527,000 to test a CRISPR-based approach to make precise changes in DNA and thereby correct (edit) three common CFTR mutations in CF: G542X, R553X, and W1282X. Each of these mutations results in a stop codon in the middle of the gene and a shorter protein that ends up getting degraded by the cells. If successful, the approach is expected to work for any mutation.

The award will support preclinical testing of an inhaled medicine that uses tiny fat particles to help the gene-editing molecules enter the cells more easily.

The awards are part of the foundations Path to a Cure, an initiative whose goal is to accelerate the development of therapeutic strategies that address the root cause of CF.

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CF Foundation Funding Bolsters Gene Therapy Research - Cystic Fibrosis News Today

Jeremy Moeller/Getty Images

Significant advancements in the treatment of relapsed or refractory large B-cell lymphoma are on the horizon. At the American Society of Hematology meeting, this weekend, both Bristol Myers Squibband Kite Pharma presented promising data from CAR-T programs aimed at this disease.

At ASH, BMS unveiled data that showedBreyanzi(liso-cel), a CD19-directed CAR-T cell therapy, as a second-line treatment in adults with relapsed or refractory large B-cell lymphoma,outperformed the current standard of carefor patients in second-line relapsed or refractory LBCL, significantly improving event-free survival (EFS). BMS said that only a small portion of patients who have relapsed or refractory large B-cell lymphoma (LBCL) experience long-term benefits with high-dose chemotherapy and stem cell transplant. Data from the pivotal Phase III TRANSFORM study showed that Breyanzi significantly improved median event-free survival with a median of 10.1 months. Standard of care treatment only offered an improvement of 2.3 months with a 65% improvement.

Data showed that 86% of Breyanzi patients achieved a complete or partial response, with 66% of patients achieving a complete response. In comparison, only 48% of standard of care patients achieved the same response, with only 39% of those reaching a complete response.

Median progression-free survival was significantly longer withBreyanzicompared to standard of care, 14.8 months vs. 5.7 months.

Additionally, results from an analysis of patient reported outcomes from the TRANSFORM study showed favorable improvement in most patient reported outcomes. That includes an improved or maintained health-related quality of life for patients who were treated with Breyanzicompared to those treated with the standard of care treatment.

Kite Pharma, a subsidiary of Gilead Sciences, showcased its own data in second-line relapsed/refractory large B-cell lymphoma (LBCL), the same indication as BMS Breyanzi. Data from the landmark Phase III ZUMA-7 study of Yescarta (axicabtagene ciloleucel) showed a 2.5 fold increase in patients who were alive at two years and had not required the need for additional cancer treatment or experienced cancer progression. Also, the data showed a four-fold greater median event-free survival for Yescarta compared to standard of care.

Kite said that improvements in EFS with Yescarta were consistent across patient subgroups, including the elderly, those with primary refractory disease, high-grade B-cell lymphoma including double-hit and triple-hit lymphoma and double expressor lymphoma.

Yescarta was the first CAR T-cell therapy to be approved by the U.S. Food and Drug Administrationfor the treatment of adult patients with relapsed or refractory large B-cell lymphoma.

Additionally, Kite announced significant long-term data showcasing the CAR-T therapys ability to provide meaningful improvements in quality of life compared with standard of care. Also at ASH, Kite unveiled data that showed Yescarta provided a five-year overall survival rate of 42%. Among those patients who saw a complete response to the CAR-T treatment, the five-year overall survival rate was 64.4%.

Perhaps most significantly, Kite said that among Yescarta patients who were still alive after five years, 92% needed no additional treatment since that first infusion of the CAR-T therapy. This suggests a potential cure for some of the patients, Kite said, in its announcement.

Other cell therapy data presented at ASH include:

bluebird Gene Therapy Improves Lives of Sickle Cell Patients

bluebird bio'slovo-celis showing promisein a Phase I/II study in sickle cell. Data from two cohorts of the largest sickle cell gene therapy program to date is showing patients treated with lovo-cel are seeing a continued complete resolution of severe vaso-occlusive events (VOE) after six years.

The VOEs are defined as episodes of acute pain with no medically determined cause other than vaso-occlusion. That means that lovo-cel, a lentiviral gene therapy, has the potential to improve day-to-day life in sickle cell patients by eliminating the painful issues associated with the disease that can occur several times per month.

Additionally, the patients have achieved near normal levels of key hemolysis markers and experienced sustained improvements in patient-reported quality of life following treatment.

The bluebird gene therapy is designed to add functional copies of a modified form of the -globin gene (A-T87Q-globin gene) into a patients blood stem cells. Once the gene is added, their red blood cells are able to produce anti-sickling hemoglobin (HbAT87Q), which reduces the sickled blood cells that cause the disease.

Janssens CAR-T Hammers Multiple Myeloma

At ASH, Janssenannounced data from a Phase Ib/II study that showed CAR-T therapy cilta-cel (ciltacabtagene autoleucel) provided anoverall response rate of 98%in patients with relapsed and/or refractory multiple myeloma.

The company said that cilta-cel, an investigational B-cell maturation antigen (BCMA)-directed CAR-T therapy, showed that patients who received an infusion continued to demonstrate deep and durable responses. Data showed that 83% of patients in the study achieved a stringent complete response (sCR) at 22 months. That is an 80% increase from the 18-month median follow-up presented earlier this year at the American Society of Clinical Oncology meeting.

Also, two-year progression free survival and overall survival rates were 61% and 74%, respectively.

Poseida Sees Promise in CAR-T as it Winds Down Autologous Program

Interim results from Poseida'sPhase I/II PRIME study of P-BCMA-101for the treatment of relapsed/refractory multiple myeloma show strong anti-tumor activity in patients with advanced forms of the disease. P-BCMA-101 in combination with rituximab achieved an improved overall response rate of 78% and 100% overall survival.

P-BCMA-101 is a non-viral transposon-based autologous CAR-T. The data from the PRIME study have been used to inform the companys development of its first allogeneic program, P-BCMA-ALLO1, also being developed in the same indication. In November, Poseida announced that it iswinding down the P-BCMA-101 autologous programin favor of the allogeneic program, P-BCMA-ALLO1.

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BMS and Kite Unveil CAR-T Successes in Lymphoma - BioSpace

Gene therapy is still in its infancy and has yet to achieve its full potential. First-generation gene therapies have been challenged by safety issues due to their inability to target cells and organs without also penetrating non-targeted cells and organs, especially the liver. Capsida's proprietary, targeted, non-invasive gene therapy technology allows more selective targeting of specific tissues and cells, overcoming many of the problems associated with first-generation gene therapies, specifically off-target cell and organ activity. In addition, it allows the gene therapy to be delivered non-invasively through intravenous (IV) administration. The company's already strong leadership team is poised to actualize the promise of gene therapy with the addition of Mr. Anastasiou and the promotions of Drs. Flytzanis and Goeden.

"I can't imagine a more exciting time to join this organization," said Mr. Anastasiou. "Capsida is enabling gene therapy to become what the industry, physicians, and patients have been dreaming it will be. Our patent-protected technology allows the targeting of cells and organs while limiting the negative impact on non-targeted areas, and can be applied across multiple therapeutic areas. Another important benefit of our technology is that we are able to deliver the gene therapy non-invasively through IV administration. I'm honored to lead this talented team to achieve Capsida's potential and to improve and even save patients' lives."

Mr. Anastasiou joins Capsida from Lundbeck, where he was an executive vice president and a member of the executive committee, reporting to the CEO. As the president of Lundbeck's U.S. and Canadian business operations, Mr. Anastasiou has built organizations from the ground up. He brings significant leadership experience managing diverse organizations and bringing them together to achieve common goals. He led as many as 1,200 employees and achieved net revenues of $1.5 billion. During his 12-year tenure at Lundbeck, Mr. Anastasiou held several progressive leadership positions, playing a pivotal role in developing and launching multiple products and building the company's cross-functional capabilities. Mr. Anastasiou serves on the Board of PhRMA and the global advisory board for the Healthcare Businesswomen's Association. Mr. Anastasiou begins his new role with Capsida on January 3, 2022.

"We're thrilled to welcome Peter as Capsida's new CEO," said Beth Seidenberg, M.D., founding managing director at Westlake Village BioPartners, one of the company's lead investors, and Capsida board member. "Peter has deep industry expertise, a broad network, and significant public company experience, which will be valuable as Capsida grows. In addition, his strong track record of success demonstrates he is a visionary leader who will be able to deliver on the promise of targeted non-invasive gene therapy to help underserved patients and achieve business success."

"During his tenure at Lundbeck, Peter has created significant shareholder value, creating and leading organizations and successful blockbuster product launches," said Clare Ozawa, Ph.D., managing director at Versant Ventures, one of Capsida's lead investors, and Capsida board member."Under Peter's leadership, we will continue to build Capsida as the industry's leading targeted, non-invasive gene therapy company with the ability to transform the lives of patients with life-threatening genetic disorders."

Prior to Lundbeck, Mr. Anastasiou held management roles at Neuronetics, Inc., Bristol-Meyers Squibb Company, and Eli Lilly and Company. He holds an MBA from the Kelley School of Business at Indiana University, and a B.A. in economics and management from Albion College.

Capsida co-founders Nicholas Flytzanis, Ph.D., promoted to CSO and Nick Goeden, Ph.D., promoted to CTO

In addition to Mr. Anastasiou's appointment, Capsida announced that Dr. Flytzanis has been promoted toCSO and Dr. Goeden has been promoted to CTO.

"The promotions of Drs. Flytzanis and Goeden are in recognition of the significant contributions they have made since co-foundingCapsida in 2019," said Mr. Anastasiou. "Their steadfast commitment to delivering on the promise of Capsida's differentiated, non-invasive gene therapy platform has been a key driver behind many of the company's early achievements."

"Drs. Flytzanis' and Goeden's strong scientific and technical expertise and know-how have already delivered results in the startup of Capsida based on Caltech'sbasic research on targeted non-invasive gene delivery to the brain," said Capsida co-founder Viviana Gradinaru, Ph.D. "Their promotions are timely as Capsida enters the phase of delivering from the lab and for the patients."

Prior to co-founding Capsida, Dr. Flytzanis served as scientific director of the CLOVER research center at the California Institute of Technology (Caltech), leading an interdisciplinary team to develop and disseminate emerging technologies focused on the cross-section of neurological research and gene therapy. His research spans the fields of tissue clearing and imaging, optogenetics and rodent behavior, and adeno-associated virus (AAV) engineering and gene therapy, with collaborations across multiple institutions. During his Ph.D., Dr. Flytzanis applied protein engineering and directed evolution across biological modalities, with a focus on developing AAVs as therapeutic tools for neurological disease.

Dr. Flytzanis holds a Ph.D. in biology from Caltech and a B.S. in biology from the Massachusetts Institute of Technology.

Prior to co-founding Capsida, Dr. Goeden led a team developing the novel adeno-associated virus (AAV) engineering technology underlying Capsida's biologically driven gene therapy platform. During his tenure as a postdoctoral fellow in Dr. Gradinaru's lab at Caltech, he developed high-throughput methods for screening combinatorial libraries to explore the AAV fitness landscape and engineered novel AAVs with high efficiency and specificity for the rodent and primate brain. During his Ph.D., Dr. Goeden developed a novel organ bioreactor to study real-time metabolomics in diseased states, exploring the relationship between gene expression and the pathophysiology of neurodevelopmental disorders.

Dr. Goeden holds a Ph.D. in neuroscience from The University of Southern California and a B.S. in biology from Caltech.

About Capsida Biotherapeutics

Capsida Biotherapeutics Inc. is an industry-leading gene therapy platform company creating a new class of targeted, non-invasive gene therapies for patients with debilitating and life-threatening genetic disorders. Capsida's technology allows for the targeted penetration of cells and organs, while limiting collateral impact on non-targeted cells and organs, especially the liver. This technology allows for the delivery of the gene therapy in a non-invasive way through intravenous administration. Capsida's technology is protected by a growing intellectual property portfolio which includes more than 30 patent applications and one issued U.S. patent 11,149,256. The company is exploring using the technology across a broad range of life-threatening genetic disorders. Its initial pipeline consists of multiple neurologic disease programs. The company has strategic collaborations with AbbVie and CRISPR, which provide independent validation of Capsida's technology and capabilities. Capsida is a multi-functional and fully integrated biotechnology company with proprietary adeno-associated virus (AAV) engineering, multi-modality cargo development and optimization, translational biology, process development and state-of-the-art manufacturing, and broad clinical development experience. Capsida's biologically driven, high-throughput AAV engineering and cargo optimization platform originated from groundbreaking research in the laboratory of Viviana Gradinaru, Ph.D., a neuroscience professor at the California Institute of Technology. Visit us at http://www.capsida.com to learn more.

SOURCE Capsida Biotherapeutics

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Capsida Biotherapeutics Poised to Capitalize on Industry-leading Gene Therapy Technology With New CEO, CSO, and CTO - PRNewswire

DUBLIN--(BUSINESS WIRE)--The "Gene Editing Global Market Report 2021: COVID-19 Growth and Change to 2030" report has been added to ResearchAndMarkets.com's offering.

The global gene editing market is expected to grow from $4.25 billion in 2020 to $4.53 billion in 2021 at a compound annual growth rate (CAGR) of 6.6%. The market is expected to reach $7.27 billion in 2025 at a CAGR of 12.6%.

Major players in the gene editing market are CRISPR, GenScript USA Inc., Horizon Discovery Group plc, Integrated DNA Technologies and New England Biolabs.

The gene editing market consists of sales of gene editing technology such as CRISPR/CAS9, zinc finger nucleus, and talens and related services. Gene editing technology allows genetic material to change genetic code at particular location in a genome. It involves cell line engineering, animal genetic engineering and plant genetic engineering.

The gene editing market covered in this report is segmented by technology into CRISPR, TALEN, ZFN. It is also segmented by end users into biotechnology, pharmaceutical, contract research organization and by application into animal genetic engineering, plant genetic engineering, cell line engineering.

Infectious diseases are constantly on the rise. For instance, according to the World Health Organization (WHO), infectious diseases kill more than 17 million people per year. In addition to that, according to the AP-NORC (a research initiative by the Associated Press and the University of Chicago) survey, out of 1,067 adults in the US surveyed, 71% are in favor of gene editing for the treatment of incurable, hereditary diseases such as Huntington's disease and 67% of Americans support the use of gene editing to prevent diseases such as cancer.

Ethical issues in general public with respect to gene editing is one of the major restraining factors for the market. Many researchers and ethicist have argued against gene editing due to different reasons such as off-target effect (edits in the wrong place), mosaicism (when only some of the cells carry the edits) and safety concerns. Some even argued that gene editing will lead to the creation of classes of individuals who will be genetically modified to be able to do things that a normal human being is not supposed to do according to the laws of nature. Due to these reasons, gene editing is still not considered to be safe and effective by many nations and international organizations.

Gene editing (also called genome editing) is a group of technologies that allow the researchers to change an organism's DNA by adding, removing or altering genetic material at particular locations in the genome. The emergence of advanced genome editing techniques is one of the major trend in the gene editing market.

The new techniques in genome editing are relatively inexpensive and can be used in a variety of application areas such as improving the food supply in agriculture, rectifying specific genetic mutations in the human genome and preventing the spread of diseases. For instance, CRISPR-Cas9 is a gene editing technique and stands for Clustered Regularly Interspace Short Palindromic Repeats.

The technique uses a strand of DNA as molecular scissors used to make cuts in DNA at specific points to make space to add new genomes. This technique is faster, cheaper, more accurate and efficient than other existing genome editing methods. Companies investing in CRISPR technology are Crispr therapeutics (CRSP), Intellia Therapeutics (NTLA), and Editas medicine.

The rising infectious diseases acts as one of the major drivers of the gene editing market. Gene editing techniques are used for detection of infectious diseases such as HIV. Infectious diseases are caused by microorganisms like bacteria, viruses, fungi, and parasites. Gene therapy treats the infectious diseases by blocking the replication of the infectious agent that causes the disease at the extracellular level. Gene editing introduces new genetic material into the cells of living organisms with the intention of treating the diseases.

European regulatory framework divided gene therapy into two categories, germline gene therapy, and somatic gene therapy. In germ line gene therapy, modified genes will be passed on to next generations whereas its not the same case with somatic gene therapy. Current regulation by the EU has only allowed somatic gene therapy, therefore, germline gene therapy is banned.

The European Medical Association provides guidelines on gene therapy for preparing market authorization application to obtain approval from the authority to carry on research and development activities in gene therapy. For instance, the EU provides guidance note on gene therapy medicinal product which is intended for use in humans, defines scientific principles and provide guidance for development and evaluation of gene therapy products.

Key Topics Covered:

1. Executive Summary

2. Gene Editing Market Characteristics

3. Gene Editing Market Trends and Strategies

4. Impact Of COVID-19 On Gene Editing

5. Gene Editing Market Size and Growth

5.1. Global Gene Editing Historic Market, 2015-2020, $ Billion

5.1.1. Drivers Of the Market

5.1.2. Restraints On the Market

5.2. Global Gene Editing Forecast Market, 2020-2025F, 2030F, $ Billion

5.2.1. Drivers Of the Market

5.2.2. Restraints On the Market

6. Gene Editing Market Segmentation

6.1. Global Gene Editing Market, Segmentation by Technology, Historic and Forecast, 2015-2020, 2020-2025F, 2030F, $ Billion

6.2. Global Gene Editing Market, Segmentation by End Users, Historic and Forecast, 2015-2020, 2020-2025F, 2030F, $ Billion

6.3. Global Gene Editing Market, Segmentation by Application, Historic and Forecast, 2015-2020, 2020-2025F, 2030F, $ Billion

7. Gene Editing Market Regional and Country Analysis

7.1. Global Gene Editing Market, Split by Region, Historic and Forecast, 2015-2020, 2020-2025F, 2030F, $ Billion

7.2. Global Gene Editing Market, Split by Country, Historic and Forecast, 2015-2020, 2020-2025F, 2030F, $ Billion

Companies Mentioned

For more information about this report visit https://www.researchandmarkets.com/r/ns9rjy

with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends.

More here:

Global Gene Editing Market Research Report 2021 Featuring CRISPR, GenScript, Horizon Discovery Group, Integrated DNA Technologies and New England...

The carbon nanotube device could streamline some cancer therapies like CAR T-cell therapy.

Researchers at the University of Rochester Del Monte Institute for Neuroscience and Rochester Institute of Technology have received a U.S. patent for technology designed to accelerate development of cell therapies for cancer and other bio-therapies. The technique provides a less toxic alternative to standard gene transfer techniques by using an array of carbon nanotubes to deliver DNA into primary neurons, immune cells, and stem cells.

Our goal is to provide a technology that can lower the cost and increase speed and the range of cell types that can be adapted for therapeutic use, said Ian Dickerson, Ph.D., associate professor of Neuroscience. Many new cell-based therapies depend on changing the gene expression of primary cells. These approaches range from stem cells for production of patient-specific repair tissues, to CAR T-cells used for focused cancer therapy.

Dickerson and Michael Schrlau, Ph.D., associate professor of mechanical engineering in RITs Kate Gleason College of Engineering, were recently awarded a patent for this technology. It delivers biomolecules into cells through carbon nanotube arrays. Their honeycomb of nanotubes device was first described in a 2016 study published in the journal Small.

A scanning electron micrograph (SEM) of a macrophage cell sitting on top of the bed of carbon nanotubes.

The carbon nanotubes aim to be an alternative to conventional gene transfer methods that have a number of limitations including expensive equipment, low efficiency, and results in high toxicity that damages the cells. These methods limit the types of experiments that can be done and many cells like stem cells, primary cells, and immune T-cells. With Dickersons and Schrlaus device cells are able to grow on the carbon nanotube, genes are then transferred through the tubes and taken up by the cells through endocytosis. It has been successful at culturing a number of cell types, including immune cells, stem cells, and neurons, all are typically difficult to grow and keep alive.

The initial research that lead to this device was supported in part by a $50-thousand SchmittProgram in Integrative Neuroscience pilot award from the Del Monte Institute for Neuroscience. It funded Dickersons project entitled High Efficiency Injection of Biomolecules into Uticle Cells by Carbon Nanotube Arrays. This funding enabled us to begin manufacturing these carbon nanotube devices, and test the function on cell lines, which provided preliminary data that proved the concept of carbon nanotube-mediated gene transfer would work, said Dickerson.

The researchers are now collaborating with investigators at Wilmot Cancer Institute to further explore using this device for cancer therapies like CAR T-cells. "Currently CART-cells are manufactured using a viral vector to accomplish gene transfer, said Patrick Reagan, M.D., assistant professor of Medicine at the Wilmot Cancer Institute.Gene transfer via carbon nanotubules represents a novel method of gene transfer that could make the manufacturingprocess more efficient. This is important given that many of the patients treated with CAR T-cell therapy for lymphoma and leukemia have aggressive disease and the time delays associated with CAR T-cell manufacturing can lead to adverse outcomes."

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URMC & RIT faculty awarded patent for gene transfer technology that could transform cancer therapies - URMC

The CGT Catapult was established to advance the growth of cell and gene therapies in the UK by bridging the gap between scientific research and full-scale commercialisation. As it prepares to open a new facility in the Edinburgh BioQuarter next summer, we put questions to its chief clinical officer Dr Jacqueline Barry.

How effective a bridge between academia and industry has CGT Catapult been?

When we were set up in 2012, there wasnt really a strong cell and gene therapy (CGT) industry. The UK is now the largest cluster for cell and gene therapies outside the United States. About 30 per cent of all CGT companies in Europe are in the UK, and the UK has representation in 12 per cent of global clinical trials. So were now becoming quite a mature industry, and the UK is known and respected globally for advanced therapies.

Our role is to create powerful collaborations which overcome challenges to the advancement of the sector. Id say weve done pretty well in bridging the gap between industry and academia, including creating new collaborations, supporting the creation of spin-out from universities and facilitating progress of companies towards commercialisation.

We continue to focus on this as a core activity for Cell and Gene Therapy Catapult.

What areas of academic need was CGT Catapult able to address?

It depends who the academics are. Some have already spun-out successful companies like Autolus Therapeutics, which announced a $250 million investment by Blackstone this month.

Another is Resolution Therapeutics, founded from a collaboration between Edinburghs Centre for Regenerative Medicine, the Scottish National Blood Transfusion Service, and Syncona Investment Management.

The company is based in the Centre for Regenerative Medicine on the Edinburgh Royal Infirmary campus. A further example would be Purespring Therapeutics, a spin-out from the University of Bristol, which secured one of the largest single investments to date for a new UK university biotech company.

While others are still relatively early in their product development path, we can use our facilities and expertise to accelerate them through the translation pathway.

We provide support through collaborative grants, for example, support of the design of a non-clinical testing programme, and provide commercialisation of research support for really promising technology or therapies to help them secure investment for their research.

How was CGT Catapult able to help industry to bring therapies closer to the market?

We try to anticipate barriers and then act to break them down. For example, a number of years ago we identified there wasnt enough cleanroom manufacturing space for late-stage clinical trials and early market release. In response to this barrier, we established our Manufacturing Innovation Centre in Stevenage, 30 miles north of London. This is a unique collaborative model, where we provide the support in the form of facility licensure, quality and warehouse management systems, environmental monitoring etc, while our collaborators can develop their processes and expertise within their own manufacturing module using their staff and processes.

Our collaborators having such space to build expertise and in-house knowledge is really valuable for them, and it cements their ability to manufacture and supply here in the UK.

In addition, we help with projects 100+ a year of different sizes and complexity, providing technology and process innovation solutions, or helping groups navigate the regulatory and reimbursement challenges and barriers.

How has CGT Catapult helped to foster a culture of innovation?

Innovation can mean so many different things. Technology and process innovation is important, and we help groups with process and analytical solutions. For example, weve taken processes with say 1,000 manual steps and automated the manufacture, increasing the security of the product.

Another could be in the clinical space. The Industrial Strategy Challenge Fund made funds available for the Advanced Therapy Treatment Centre network. This is truly innovative. Were working with 65 industry partners alongside the NHS to come up with solutions for these innovative but disruptive products for patients. Working hand-in-hand with industry and the NHS, we are innovating together, producing practical solutions for both parties.

What are the challenges for the NHS with these kinds of products?

These are living therapies, its disruptive and difficult to deliver these products. In addition, there is an avalanche of products coming with different product types for different indications and different patient groups.

Specialists might not be familiar with these new products. There are often complex referral pathways, so theyre only delivered from particular hospitals. There are specific regulatory and reimbursement conditions placed on the manufacturers. All these things together add complexity and require innovative solutions to not increase the burden for the NHS.

The CGT Catapult aims to help cell and gene therapies to be safer, more effective, scalable and affordable. How do you maintain research integrity and best practice in the face of that constant demand to do things better, faster, cheaper?

Were all scientists and we know this is a young field which has great promise. I think its just in everybodys DNA to ensure that your data integrity is as solid as it possibly can be.

These are quite unusual products which are designed to treat patients who are either at the end of their treatment regimen for example, treatment of a blood cancer or for the treatment of rare genetic disorders, and you want to catch their symptoms before they start impacting on their day-to-day life. So you have to act quickly, but be really confident that your data supports the use of these products.

Why is CGT Catapult coming to Edinburgh [in summer 2022]? Whats it adding?

A lot of cell and gene therapy work is currently focused in southern England, where we have also seen the third-largest cell and gene therapy cluster developing around Stevenage. There are, however, opportunities for growth and further cluster development across the UK, creating jobs and offering equity of access for patients through the UK.

The CGT Catapult will have offices and labs based in the Institute for Regeneration and Repair in the Bioquarter, Edinburgh. The University of Edinburgh and Scottish Blood Transfusion Service have considerable expertise in the development of cell and gene therapy products. Between the Scottish Centre for Regenerative Medicine and the Institute for Regeneration and Repair [currently under construction in the BioQuarter], the University of Edinburgh will have 500 stem cell scientists. Thats the biggest accumulation of stem cell scientists in Europe, and possibly the world.

Pluripotent stem cells [cells with the capacity to develop into all cell types] offer new possibilities for off-the-shelf products. The Cell and Gene Therapy Catapult will work with these scientists to develop their products and accelerate them through clinical trials and become investable propositions, whether through spin-out companies or investment by big pharma.

In addition, we want to work with the NHS, academics, industry and the whole life sciences community to make the best potential of the wealth of experience in the Central Belt of Scotland and use it for the advantage for all of the UK.

Whats the future vision for CGT Catapult?

Our vision is a thriving industry delivering life changing advanced therapies to the world. For the UK to remain one of the most important players globally for these advanced cell and gene therapies.

We want the UK to be at the forefront of manufacture and supply of these living therapies. We want our NHS to be able to adopt them quickly and ensure they get to the right patients as quickly as possible. The UK, thanks to its favourable ecosystem including CGT Catapults activities and continued impact on it, and the continuous support by government for innovation, can stay at the forefront of that.

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Bridging the cell and gene therapy gap - The Scotsman

PARIS--(BUSINESS WIRE)--Regulatory News:

GenSight Biologics (Euronext: SIGHT, ISIN: FR0013183985, PEA-PME eligible), a biopharma company focused on developing and commercializing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders, today reported topline efficacy and safety results at 2 years post-treatment administration in the REFLECT Phase III clinical trial with LUMEVOQ. The results show sustained efficacy and safety for bilateral intravitreal injection of the gene therapy, including better efficacy compared to unilateral injection.

The findings reinforce the results observed at 1.5 years post-treatment administration, which were reported in June 2021.

The REFLECT trials demonstration of a sustained, significant and safe improvement in visual acuity for LHON patients treated bilaterally with LUMEVOQ provides additional impetus for our push to gain regulatory approval, said Bernard Gilly, CEO and Co-Founder of GenSight Biologics. Patients afflicted with LHON who are losing their sight deserve access to a treatment like LUMEVOQ.

Designed under a Special Protocol Assessment with the FDA, REFLECT is a randomized, double-masked, placebo-controlled Phase III trial involving 98 subjects with vision loss due to Leber Hereditary Optic Neuropathy (LHON) caused by a mutated ND4 mitochondrial gene; enrolled ND4 subjects had vision loss up to one year from onset. The ND4 mitochondrial mutation is associated with the most severe clinical form of LHON, with poor overall visual outcomes.1 All subjects received an intravitreal injection (IVT) of LUMEVOQ in their first affected eye. The second affected eye was randomized to either a second IVT of LUMEVOQ or a placebo IVT, which was administered on the same day or the following day. 48 subjects were randomized to LUMEVOQ bilateral treatment, and 50 to LUMEVOQ unilateral treatment (first-affected eye treated with LUMEVOQ, second-affected eye treated with placebo).

Significant visual acuity improvement over baseline, with better results for bilaterally injected patients

Two years after injection, the mean best-corrected visual acuity (BCVA) in LUMEVOQ-treated eyes was statistically significantly better than baseline, whereas the improvement from baseline was not statistically significant in placebo-treated eyes. The results indicate a sustained treatment effect for all subjects, with the improvement being greater among bilaterally treated patients.

Table 1: Change in Best-Corrected Visual Acuity (BCVA) versus Baseline, 2 Years after Injection

1st affected eye

2nd affected eye

Subjects bilaterallyinjected with LUMEVOQ

LUMEVOQ-0.25 LogMAR+13 ETDRS lettersp=0.0006

LUMEVOQ-0.18 LogMAR+9 ETDRS lettersp=0.01

Subjects unilaterallyinjected with LUMEVOQ

LUMEVOQ-0.16 LogMAR+8 ETDRS lettersp=0.02

PLACEBO-0.10 LogMAR+5 ETDRS lettersp=0.1 (NS)

The contralateral effect observed with placebo at 2 years is consistent with that which was documented in sham-treated eyes in the REVERSE2 and RESCUE3 trials.

Year 2 analyses also confirm the dose effect that was noted at Year 1.5: the mean BCVA at 2 years for bilaterally and unilaterally treated subjects reached 1.32 and 1.44 LogMAR, respectively, with an absolute difference between arms of +6 ETDRS letters in favor of bilaterally treated subjects.

Responder analyses point to the benefits of treatment for patients that would otherwise have experienced significant vision loss with a very low likelihood of spontaneous recovery.1 For example, 60% of the bilaterally treated patients (56% of unilaterally treated patients) who had vision above the threshold of legal blindness in at least one eye remained above the threshold at Year 2.

Efficacy demonstrated even more clearly in visual acuity improvement from nadir

Comparison against nadir (i.e., the worst BCVA recorded from baseline to Year 2) more starkly demonstrates the efficacy of LUMEVOQ, even for the placebo eyes that improved via a contralateral treatment effect.

Table 2: Change in Best-Corrected Visual Acuity (BCVA) versus Nadir, 2 Years after Injection

1st affected eye

2nd affected eye

Subjects bilaterallyinjected with LUMEVOQ

LUMEVOQ-0.39 LogMAR+20 ETDRS lettersp<0.0001

LUMEVOQ-0.34 LogMAR+17 ETDRS lettersp<0.0001

Subjects unilaterallyinjected with LUMEVOQ

LUMEVOQ-0.38 LogMAR+19 ETDRS lettersp<0.0001

PLACEBO-0.27 LogMAR+14 ETDRS lettersp<0.0001

Responder analyses indicate that the treatment effect is not limited to just a minority of subjects. Two years after injection, 73% of bilaterally treated subjects and 66% of unilaterally treated subjects had experienced a clinically meaningful improvement of at least -0.3 LogMAR (+15 ETDRS letters) relative to their observed nadir.

Table 3: Responder Analyses, Based on Change from Nadir at Year 2

Definition of Responder

-0.3 LogMAR improvement inat least one eye

Clinically Relevant Recovery*in at least one eye

Subjects bilaterallyinjected with LUMEVOQ

73%

75%

Subjects unilaterallyinjected with LUMEVOQ

66%

60%

Note: *Clinically Relevant Recovery is defined as: i) For eyes on-chart at nadir, an improvement of -0.2 LogMAR (10 ETDRS letters) from nadir; or ii) For eyes off-chart at nadir, eyes which became on-chart (i.e., BCVA 1.6 LogMAR).

Bilateral injections have a favorable safety profile

The favorable safety profile of LUMEVOQ was confirmed. There was no study discontinuation related to systemic or ocular adverse events, and there were no serious ocular adverse events. The main ocular adverse event was intraocular inflammation, which was mostly mild and responsive to conventional treatment. The favorable safety profile was comparable in unilaterally and bilaterally treated subjects.

The persistence of LUMEVOQ efficacy is remarkably consistent across the development program, so that the REFLECT results bolster the evidence provided by 3 years of data from RESTORE4 and 5 years of data from REVEAL, noted Magali Taiel, MD, Chief Medical Officer of GenSight Biologics.

Results of the 4-year follow-up of RESTORE are expected to be available in January 2022.

Dr. Taiel added, Moreover, we affirm the insight that bilateral injection of LUMEVOQ is the best option for patients with ND4 Leber Hereditary Optic Neuropathy.

REFLECT patients have been invited to participate in a long-term follow-up that will monitor the safety and efficacy of LUMEVOQ up to 5 years post-injection.

References:

About GenSight Biologics

GenSight Biologics S.A. is a clinical-stage biopharma company focused on developing and commercializing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders. GenSight Biologics pipeline leverages two core technology platforms, the Mitochondrial Targeting Sequence (MTS) and optogenetics, to help preserve or restore vision in subjects suffering from blinding retinal diseases. GenSight Biologics lead product candidate, LUMEVOQ (GS010; lenadogene nolparvovec), has been submitted for marketing approval in Europe for the treatment of Leber Hereditary Optic Neuropathy (LHON), a rare mitochondrial disease affecting primarily teens and young adults that leads to irreversible blindness. Using its gene therapy-based approach, GenSight Biologics product candidates are designed to be administered in a single treatment to each eye by intravitreal injection to offer subjects a sustainable functional visual recovery.

About Leber Hereditary Optic Neuropathy (LHON)

Leber Hereditary Optic Neuropathy (LHON) is a rare maternally inherited mitochondrial genetic disease, characterized by the degeneration of retinal ganglion cells that results in brutal and irreversible vision loss that can lead to legal blindness, and mainly affects adolescents and young adults. LHON is associated with painless, sudden loss of central vision in the 1st eye, with the 2nd eye sequentially impaired. It is a symmetric disease with poor functional visual recovery. 97% of subjects have bilateral involvement at less than one year of onset of vision loss, and in 25% of cases, vision loss occurs in both eyes simultaneously. The estimated incidence of LHON is approximately 1,200-1,500 new subjects who lose their sight every year in the United States and the European Union.

About LUMEVOQ (GS010; lenadogene nolparvovec)

LUMEVOQ (GS010; lenadogene nolparvovec) targets Leber Hereditary Optic Neuropathy (LHON) by leveraging a mitochondrial targeting sequence (MTS) proprietary technology platform, arising from research conducted at the Institut de la Vision in Paris, which, when associated with the gene of interest, allows the platform to specifically address defects inside the mitochondria using an AAV vector (Adeno-Associated Virus). The gene of interest is transferred into the cell to be expressed and produces the functional protein, which will then be shuttled to the mitochondria through specific nucleotidic sequences in order to restore the missing or deficient mitochondrial function. LUMEVOQ was accepted as the invented name for GS010 (lenadogene nolparvovec) by the European Medicines Agency (EMA) in October 2018.

About REFLECT

REFLECT is a multi-center, randomized, double-masked, placebo-controlled study to evaluate the safety and efficacy of bilateral injections of GS010 in subjects with LHON due to the NADH dehydrogenase 4 (ND4) mutation. In the active arm, GS010 was administered as a single intravitreal injection in each eye of each subject. In the placebo arm, GS010 was administered as a single intravitreal injection to the first affected eye, while the fellow eye received a placebo injection.

The primary endpoint for the REFLECT trial is the BCVA reported in LogMAR at 1.5 years (78 weeks) post-treatment in the second-affected/not-yet-affected eye. The change from baseline in second-affected/not-yet-affected eyes receiving GS010 and placebo is the primary response of interest. The secondary efficacy endpoints include: BCVA reported in LogMAR at 2 years post-treatment in the second-affected/not-yet-affected eye compared to both placebo and the first-affected eye receiving GS010, OCT and contrast sensitivity and quality of life scales.

The trial was conducted in multiple centers across Europe (1 each in France, Spain, Italy and the UK), the US (6 centers) and Taiwan (1 center). The trial planned to enroll 90 subjects with vision loss up to 1 year in duration; 98 subjects were successfully screened and treated. The first subject was treated in March 2018 and the last one in July 2019.

ClinicalTrials.gov Identifiers:REFLECT: NCT03293524

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GenSight Biologics Confirms Sustained Efficacy and Safety of Bilateral LUMEVOQ Injections at 2-Year Follow-Up of REFLECT Phase III Trial - Business...

A group of gene therapy experts called for better research tools and more careful monitoring of side effects to treatment, but stopped short in a high-profile meeting Thursday of advocating for major changes to how studies in the fast-growing field are conducted.

The committee, which the Food and Drug Administration convened for advice on the risks to gene therapy, proposed a number of ways research could potentially be made safer, such as by improving how patients are screened for clinical trials. None of the panel members, though, suggested slowing research in any significant fashion, rejecting, for instance, the idea of imposing an upper limit on gene therapy doses to lower risks.

"While the meeting was an excellent update on pre-clinical and clinical adverse events in the field, it largely left untouched what measures might actually be taken to help future-proof this field," said Anthony Davies, founder and CEO of Dark Horse Consulting, which specializes in gene therapy.

Experts said that inconsistent standards in how gene therapies are produced, and how certain safety risks are assessed, made it difficult to come up with recommendations that could be broadly applied.

The meeting, which will continue Friday, comes after a series of safety incidents in gene therapy clinical trials resurfaced some longstanding concerns, as well as new worries about the use of high treatment doses. The deaths last year of three children in a study of a neuromuscular disease therapy, in particular, appear to have spurred the FDA to seek the experts' advice.

"Our enthusiasm for this field must be balanced by caution," said Wilson Bryan, director of the FDA's Office of Tissues and Advanced Therapies, in a presentation opening the meeting Thursday. "The greatest risks in drug development fall on the patients who receive an investigational product."

The FDA split the first day of the meeting into two sessions, focusing the first on the persistent worry that injecting genes into cells might eventually spur cancer, and the second on the liver injury that can be caused by treatment. The committee will discuss brain toxicity Friday.

In discussing the risk of cancer, experts spent considerable time weighing findings from testing in animals, some of which dates back more than 20 years. Results have shown that a commonly used delivery tool, the adeno-associated virus or AAV, can fuse itself into the genomes of certain animals and, at least in mice, that integration is associated with liver cancer.

Concerns around whether this risk can play out similarly in humans grew earlier this year when a patient given an experimental hemophilia gene therapy developed by the biotech company UniQure was diagnosed with liver cancer.

UniQure has since exonerated its gene therapy, and experts at the FDA panel noted the risk remains theoretical. Other research in larger animals and in humans haven't replicated the worrisome findings in mice. A study following dogs given a hemophilia gene therapy and presented at the meeting by University of Pennsylvania researcher Denise Sabatino, for example, showed AAV did get into the genome but didn't lead to cancer.

"[T]his is something that will need to be monitored very carefully, [but] so far, the signal in the clinic doesn't seem to be very strong," said Christopher Breuer, the director of the center for regenerative medicine at Nationwide Children's Hospital, a top gene therapy hub.

Pfizer, which has invested heavily in gene therapy, argued companies shouldn't have to run more studies looking for integration events in animals until there is "clear causality in humans," according to a public comment filed with the FDA. Pfizer claimed additional experiments using human cell lines to assess risk would be more relevant.

FDA panelists, meanwhile, said longer animal tests might more effectively capture any cancer risk of AAV, as will tracking the health of the more than 800 children who have so far received the Novartis spinal muscular atrophy treatment Zolgensma. Experts also suggested closer scrutiny of gene therapy components.

But several were hesitant to make broad recommendations to the FDA as there aren't set rules for every aspect of how gene therapies are made.

"We are starting to get a sense of the scientific issues that are out there, but we need to start to drive towards some type of standardization," said Taby Ahsan, the head of biologics analytical development at MD Anderson Cancer Center. "Understanding that will help us give solid recommendations for preclinical study design as we move forward."

While the cancer risk of AAV gene therapy in humans remains theoretical, liver toxicity is one of the most common side effects reported in clinical testing to date and, in a few cases, has led to serious health problems.

In a study of a gene therapy developed by Audentes Therapeutics, for instance, three young children given a very high dose developed liver damage and later died, although the exact link between their deaths and the treatment is still unclear. Two cases of acute liver failure have also been reported in patients treated with Zolgensma, and many hemophilia patients across several gene therapy studies have experienced significant increases in liver enzyme counts, a potentially worrisome sign.

"I think that a lot of the studies have missed opportunities to involve hepatologists early on," said Theo Heller, a liver specialist at the National Institute of Diabetes and Digestive and Kidney Diseases, at the meeting. "Hepatotoxicity is such a common side effect of this therapy."

Experts did call on researchers to more comprehensively assess and screen for preexisting liver conditions, which they said might affect how side effects develop.

"We do need careful screening," said Lisa Butterfield, the meeting's chair and vice president of the Parker Institute for Cancer Immunotherapy at the University of California, San Francisco. "We need to focus on more than just fluctuations in blood work."

The committee made few other concrete recommendations on how best to manage the risk of liver problems, though. In particular, they opposed placing an upper limit on the gene therapy doses that could be tested, although research suggests the worst health consequences to liver toxicity only emerge at higher doses.

A major sticking point, some members noted, was the difficulty in characterizing the make-up of gene therapy doses, which can contain extraneous material alongside the therapeutic DNA.

"It confounds this question of toxicity and toxic side effects of AAV perhaps because, again, going back, we don't have reference standards for the field," said Charles Venditti, a senior investigator with the National Human Genome Research Institute.

Read more:

At FDA meeting, gene therapy experts wrestle with field's blindspots - BioPharma Dive