Archive for the ‘Gene Therapy Research’ Category

- Company announces clearance of IND application with FDA for anti-tau antibody VY-TAU01 for the treatment of Alzheimers disease; expect to begin single ascending dose trial in the coming weeks -

- Development candidates selected for Neurocrine-partnered GBA1 and Friedreichs Ataxia gene therapy programs; potential for three gene therapies, including SOD1-ALS, to enter the clinic in 2025 -

- Appointed neurology clinical development expert Toby Ferguson, M.D., Ph.D., as Chief Medical Officer -

- Strong cash position of approximately $400 million as of March 31, 2024; expected to provide runway through multiple clinical data readouts into 2027 -

LEXINGTON, Mass., May 13, 2024 (GLOBE NEWSWIRE) -- Voyager Therapeutics, Inc. (Nasdaq: VYGR), a biotechnology company dedicated to advancing neurogenetic medicines, today reported first quarter 2024 financial and operating results.

We have obtained IND clearance for our anti-tau antibody VY-TAU01 for Alzheimers disease, and we expect to dose the first subject in our single ascending dose trial in healthy volunteers in the coming weeks, said Alfred W. Sandrock, Jr., M.D., Ph.D., Chief Executive Officer of Voyager. Our gene therapy pipeline is also advancing, with development candidates selected in the GBA1 and Friedreichs Ataxia programs partnered with Neurocrine, as well as in our wholly-owned SOD1-ALS program. We expect to achieve IND filings for all three of these gene therapy programs in 2025. We maintain a strong cash position of approximately $400 million at quarter-end, with runway into 2027, which we anticipate will enable us to reach multiple data readouts in 2025 and 2026.

First Quarter 2024 and Recent Highlights

Anticipated Upcoming Milestones

First Quarter 2024 Financial Results

Financial Guidance

Voyager is committed to maintaining a strong balance sheet that supports the advancement and growth of its platform and pipeline. Voyager continues to assess its planned cash needs both during the current period and in future periods. We expect our cash, cash equivalents, and marketable securities, along with amounts expected to be received as reimbursement for development costs under the Neurocrine and Novartis collaborations, certain near-term milestones, and interest income, to be sufficient to meet Voyagers planned operating expenses and capital expenditure requirements into 2027.

Conference Call

Voyager will host a conference call and webcast today at 4:30 p.m. ET to discuss first quarter 2024 financial and operating results. To participate via telephone and join the call live, please register in advance here: https://register.vevent.com/register/BI1f6af80e7a614ca7925cbad2f35a55c6. Upon registration, telephone participants will receive a confirmation email detailing how to join the conference call, including the dial-in number and a unique passcode. A live webcast of the call will also be available on the Investors section of the Voyager website at ir.voyagertherapeutics.com, and a replay of the call will be available at the same link approximately two hours after its completion. The replay will be available for at least 30 days following the conclusion of the call.

About the TRACER Capsid Discovery Platform

Voyagers TRACER (Tropism Redirection of AAV by Cell-type-specific Expression of RNA) capsid discovery platform is a broadly applicable, RNA-based screening platform that enables rapid discovery of novel AAV capsids to enable gene therapy. Voyager has leveraged TRACER to create multiple families of novel capsids that, following intravenous delivery in preclinical studies, harness the extensive vasculature of the central nervous system (CNS) to cross the blood-brain barrier and transduce a broad range of CNS regions and cell types. In cross-species preclinical studies (rodents and multiple non-human primate species), intravenous delivery of TRACER-generated capsids resulted in widespread payload expression across the CNS at relatively low doses, enabling selection of multiple development candidates in Voyagers wholly-owned and partnered gene therapy programs for neurologic diseases.

About Voyager Therapeutics

Voyager Therapeutics, Inc. (Nasdaq: VYGR) is a biotechnology company dedicated to leveraging the power of human genetics to modify the course of and ultimately cure neurological diseases. Our pipeline includes programs for Alzheimers disease, amyotrophic lateral sclerosis (ALS), Parkinsons disease, and multiple other diseases of the central nervous system. Many of our programs are derived from our TRACER AAV capsid discovery platform, which we have used to generate novel capsids and identify associated receptors to potentially enable high brain penetration with genetic medicines following intravenous dosing. Some of our programs are wholly owned, and some are advancing with partners including Alexion, AstraZeneca Rare Disease; Novartis Pharma AG; Neurocrine Biosciences, Inc.; and Sangamo Therapeutics, Inc. For more information, visit http://www.voyagertherapeutics.com.

Voyager Therapeutics is a registered trademark, and TRACER is a trademark, of Voyager Therapeutics, Inc.

Forward-Looking Statements

This press release contains forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995 and other federal securities laws. The use of words such as expect, will, believe, anticipate, potential, trigger or continue, and other similar expressions are intended to identify forward-looking statements.

For example, all statements Voyager makes regarding Voyagers ability to advance its AAV-based gene therapy programs and tau antibody program, including expectations for Voyagers achievement of preclinical and clinical development milestones for its potential development candidates such as IND filings, the initiation of clinical trials, and generation of clinical data and proof-of-concept; Voyagers ability to advance gene therapy product candidates under the Neurocrine and Novartis collaborations; Voyagers anticipated financial results, including the anticipated receipt by Voyager of revenues or reimbursement payments from collaboration partners; and Voyagers cash runway and ability to generate sufficient cash resources to enable it to continue its business and operations are forward looking.

All forward-looking statements are based on estimates and assumptions by Voyagers management that, although Voyager believes such forward-looking statements to be reasonable, are inherently uncertain. All forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those that Voyager expected. Such risks and uncertainties include, among others, the expectations and decisions of regulatory authorities; the timing, initiation, conduct and outcomes of Voyagers preclinical and clinical studies; the availability of data from clinical trials; the availability or commercial potential of product candidates under collaborations; the willingness and ability of Voyager's collaboration partners to meet obligations under collaboration agreements with Voyager; the continued development of Voyagers technology platforms, including Voyagers TRACER platform and its antibody screening technology; Voyagers scientific approach and program development progress, and the restricted supply of critical research components; the development by third parties of capsid identification platforms that may be competitive to Voyagers TRACER capsid discovery platform; Voyagers ability to create and protect intellectual property rights associated with the TRACER capsid discovery platform, the capsids identified by the platform, and development candidates for Voyagers pipeline programs; the possibility or the timing of Voyagers receipt of program reimbursement, development or commercialization milestones, option exercise, and other payments under Voyagers existing licensing or collaboration agreements; the ability of Voyager to negotiate and complete licensing or collaboration agreements with other parties on terms acceptable to Voyager and the third parties; the success of programs controlled by third party collaboration partners in which Voyager retains a financial interest, and the success of Voyagers product candidates; the ability to attract and retain talented directors, employees, and contractors; and the sufficiency of cash resources to fund its operations and pursue its corporate objectives.

These statements are also subject to a number of material risks and uncertainties that are described in Voyagers most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission. All information in the press release is as of the date of this press release, and any forward-looking statement speaks only as of the date on which it was made. Voyager undertakes no obligation to publicly update or revise this information or any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law.

Contacts

Trista Morrison, NACD.DC, tmorrison@vygr.com Investors: Adam Bero, Ph.D., abero@kendallir.com Media: Brooke Shenkin, brooke@scientpr.com

GAAP vs. Non-GAAP Financial Measures Voyagers financial statements are prepared in accordance with generally accepted accounting principles in the United States, or GAAP, and represent revenue and expenses as reported to the Securities and Exchange Commission. Voyager has provided in this release certain financial information that has not been prepared in accordance with GAAP, including net collaboration revenue and net research and development expenses, which exclude the impact of reimbursement by Neurocrine Biosciences (Neurocrine) for expenses we incur in conducting preclinical development activities under our collaboration agreements. Management uses these non-GAAP measures to evaluate the Companys operating performance in a manner that allows for meaningful period-to-period comparison and analysis of trends in its business. Management believes that such non-GAAP measures are important in comparing current results with prior period results and are useful to investors and financial analysts in assessing the Companys operating performance. Non-GAAP financial measures are not required to be uniformly applied, are not audited and should not be considered in isolation. The non-GAAP measures give investors and financial analysts a better understanding of our net revenue and net research and development expenses without the pass-through impact of Neurocrine costs. The non-GAAP financial information presented here should be considered in conjunction with, and not as a substitute for, the financial information presented in accordance with GAAP. Investors are encouraged to review the reconciliation of these non-GAAP measures to their most directly comparable GAAP financial measures set forth below.

Note 1: Under the Company's existing collaboration agreements with Neurocrine and Novartis, Neurocrine and Novartis have agreed to be responsible for all costs the Company incurs in conducting preclinical development activities for certain collaboration programs, in accordance with joint steering committee agreed upon workplans and budgets. Reimbursable research and development services performed during the period are captured within collaboration revenue and research and development expenses in the Company's consolidated statements of operations. During the three months ended March 31, 2024, we incurred $3.2 million of reimbursable research and development services recorded within collaboration revenue and research and development expenses. During the three months ended March 31, 2023, we incurred $0.3 million of reimbursable research and development services recorded within collaboration revenue and research and development expenses.

Link:
Voyager Therapeutics Reports First Quarter 2024 Financial and Operating Results - GlobeNewswire

Ace Therapeutics announced the unveiling of its gene therapy development services to advance glaucoma research. To advance glaucoma research, Ace Therapeutics, an integrated biotechnology company with a broad research scope and comprehensive services, has announced the unveiling of its gene therapy development services. The company's innovative gene therapy approach holds promise in providing a new, effective treatment option for individuals suffering from this eye disease that damages the optic nerve.

Glaucoma is a leading cause of irreversible blindness worldwide, and currently available treatments only offer temporary relief of symptoms. Studies have found the main risk factor for glaucoma is high IOP, primarily due to RGC injury and death. For this reason, Ace Therapeutics offers glaucoma gene therapy development [https://www.acetherapeutics.com/glaucoma/gene-therapy-development-for-glaucoma.html] services, targeting IOP and RGC-associated candidate genes, as well as many other related genes and pathways. By delivering therapeutic nucleic acids directly to the affected cells, the company's gene therapy has the potential to halt the progression of glaucoma and preserve vision for patients.

Considering the great potential of stem cells as a possible therapy for glaucoma, the expert team at Ace Therapeutics can provide specialized services in glaucoma drug development, offer the opportunity to develop drugs for glaucoma using stem cell technology and stem cell-based therapies to restore vision loss due to glaucoma. In addition, the company also utilizes siRNA-based gene silencing strategies to treat glaucoma, providing researchers with development services to study the composition and mechanisms of siRNA drugs, offering solutions to the fundamental challenges faced during development.

"We are excited to collaborate with worldwide researchers to develop a more effective treatment for glaucoma using our gene therapy expertise and technologies," said the senior scientist at Ace Therapeutics. "We can provide genomic analysis or directly select appropriate genes from candidate genes that are genetically linked to glaucoma to those involved in the relevant pathway. Also, we can develop gene delivery systems for glaucoma gene therapy to ensure the transfer of nucleic acid drugs to target cells and to advance the translational application of gene therapy."

About Ace Therapeutics

Ace Therapeutics Glaucoma [https://www.acetherapeutics.com/glaucoma/] is an innovative ophthalmic disease research company that offers a wide range of services in basic research, drug development and preclinical studies, delivering innovative and high-quality solutions to global clients. Ace Therapeutics' mission is to be a leader in the field of glaucoma research, providing unique drug development, and preclinical research solutions to advance researchers' project development.

Media Contact Company Name: Ace Therapeutics Contact Person: Daisy Mostert Email:Send Email [https://www.abnewswire.com/email_contact_us.php?pr=ace-therapeutics-unveils-gene-therapy-development-services-to-fuel-glaucoma-research] Country: United States Website: https://www.acetherapeutics.com/

This release was published on openPR.

See original here:
Ace Therapeutics Unveils Gene Therapy Development Services to Fuel Glaucoma Research - openPR

From an early age, Allison Keeler 05 (biotechnology) always knew she wanted to be a scientist. As an adult, that dream has come true as she is an assistant professor in the Department of Pediatrics at the University of Massachusetts (UMass) Chan Medical School and the lead researcher in the Keeler Lab within the Horae Gene Therapy Center.

Keeler applied early to RIT, out of her high school in eastern Pennsylvania. After visiting the campus and learning the university had one of the few biotechnology programs available, she knew getting hands-on experience in research at RIT was the best path for her future.

Keeler earned her bachelors degree in three years and was able to take advantage of a trip to the Galpagos Islands, where she realized she wanted to become an academic and a professor. After a research position at Duke University, she earned her Ph.D. in biomedical sciences from the UMass Medical School, where she now works. Mentoring and teaching in a lab environment has become her passion.

Basics that I learned at RIT and each of my experiences have shaped where I am now and what Im really passionate about, said Keeler.

Her background has led her to one of the most revolutionary medical fields today: gene therapy. This technology approaches disease differently, by attempting to change genetic makeups to prevent and treat disease instead of traditional treatments like medication and surgery.

In her lab, Keeler is learning about and understanding immune responses to gene therapy and engineering and developing new novel gene therapies for the treatment of different diseases.

The field is progressing rapidly. When she was a graduate student, there were no approved therapies. Now, there are many, with more being approved every year.

Its been really interesting to watch the field evolve, said Keeler. Its an exciting time in this field because several gene therapies have recently been approved.

The scientific area is familiar to the dean of RITs College of Science, Andr Hudson, who is repeatedly sought out as an expert in biochemistry and microbiology. His research interests are closely related to Keelers, as both are excited about the future of science as it relates to the human body and disease.

The work by Dr. Keeler and colleagues in this space is at the forefront of science and medicine, said Hudson. I am heartened that one of our College of Science alumni is helping to lead the charge.

Keeler never envisioned she would be running her own gene therapy lab when she stepped on RITs campus as a biotechnology major. But as science grows and evolves, more and more possibilities for careers in science exist. She encourages students to keep their minds open and to explore all opportunities.

I didnt even know about gene therapy when I was at RIT, said Keeler. But science continues to expand. Keep being curious, keep asking questions.

See the original post:
Scientist's RIT experience leads to career in revolutionary gene therapy research | RIT - Rochester Institute of Technology

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Good morning! A crowdsourced Readout today, to be sure, with contributions from STATs Jason Mast, Elaine Chen, and Jonathan Wosen. We get into earnings from Novo Nordisk, Amgen, and Illumina, and see that ICER is not so enthused about a gene therapy from Sarepta.

Also: Wed like to know what you think of this newsletter. if you havent, could you fill outthis survey?

Novo Nordisk CEO Lars Fruergaard Jrgensen is standing by the cost of Ozempic and Wegovy, despite an ongoing Senate investigation into the companys pricing. In an earnings call yesterday, he said the drugs offer an attractive value proposition as theyre priced similarly to earlier, less effective iterations of this class of drugs.

Although he conceded that the number of people taking the drugs is to some degree putting strains on health care systems, STATs Elaine Chen writes, the full value of these diabetes and obesity drugs has yet to be realized. Ozempics list price is $969 monthly; Wegovys is $1,349. Executives on the call said that the net prices for these drugs have already come down, and will continue to do so as more people take it and as competition increases.

Read more.

The removal of small amounts of brain tissue from desperately ill patients, done as part of a Mount Sinai research project, triggered alarm bells at the FDA and has raised broader questions about the scientific and ethical justification for live-brain research. Journalist and STAT contributor Katherine Eban joins The Readout LOUD this week to discuss the findings of atwo-year investigation.

Also on this weeks episode, STATs Adam Feuerstein and Allison DeAngelis discuss Novartis effort to acquire MorphoSys, and the latest news on Eli Lilly and Novo Nordisks blockbuster obesity drugs with Elaine Chen.

Listen here.

From STATs Jason Mast:The drug-pricing watchdogs over at the Institute for Clinical and Economic Review, or ICER, often take a dim view of modern drug pricing exceptwhen it comes to genetherapy. Those treatments, the nonprofit has said, often provide the years-long benefits for severe disease that justify a multimillion-dollar price tag.

Which makes theJAMApiecepublishedthis week by ICER CMO David Rind all the more notable. Rind considered Elevidys, Sareptas $3.2 million gene therapy for Duchenne muscular dystrophy. The treatment was given accelerated approval last year for 4- and 5-year-olds and, after a Phase 3 trial, the FDA is now considering whether to approve it for all ages.

That Phase 3 trial missed its primary endpoint, though, as did a previous smaller study. Sarepta has pointed to the results on secondary measures but given those data, Rind cast doubt on whether it should be approved and certainly whether Sarepta should charge what other gene therapy companies do. This is an enormous price tag for a therapy that has failed to meet its primary end point in the 2 randomized trials in which it has been studied and that is clearly not curative, he wrote.

From STATs Jonathan Wosen:DNA sequencing juggernaut Illumina reported yesterday $1.06 billion in revenue for its core business during the first quarter of this year, down 2% from the same time last year, with the companys execs reiterating that they expect 2024 revenue to essentially match the $4.5 billion from the previous fiscal year.

CEO Jacob Thaysen cautiously described the first-quarter numbers as a decent start to the year that exceeded expectations on a call with market analysts and investors. The updated numbers come during a turbulent time for the broader sequencing space. Pacific Biosciences, a Bay Area company that Illumina once unsuccessfully tried to acquire, recently laid off nearly 200 employees after reporting disappointing first-quarter sales. And while Illumina continues to control about 80% of the market, its shares are down 37% from a year ago and the firm faces growing competition from players such asUltima, Singular Genomics, andElement Biosciences.

The San Diego genomics giant is still on track to finalize the terms of its divestiture of Grail a cancer detection startup Illumina had acquired for $8 billion, drawing the ire of regulators in the U.S. and Europe by the end of the second quarter of this year.

From STATs Elaine Chen:Amgen will scrap an early-stage obesity pill, and will instead focus on its more advanced injectable candidate called MariTide thats seen as a potential competitor to Wegovy and Zepbound.

MariTide is in a Phase 2 trial for obesity, and CEO Bob Bradway said on the earnings call yesterday that we are very encouraged with the results from an interim analysis of that trial. The company is planning a broad Phase 3 program that will study MariTide in obesity, diabetes, and obesity-related conditions, and its already gearing up to make large amounts of the drug, initiating activities to further expand manufacturing capacity with both clinical and commercial supply in mind, Bradway said.

MariTide has an interesting mechanism its a monoclonal antibody linked to two peptides that activates receptors of the GLP-1 hormone while blocking receptors of the GIP hormone. Even though that appears to contradictory to the mechanism of Lillys potent obesity drug Zepbound, which activates both GLP-1 and GIP receptors, MariTide has shown potential to induce potent and longer-lasting weight loss.

Read more.

See the rest here:
Readout Newsletter: Amgen, Illumina, Novo Nordisk, and more - STAT

SMN-K186R, a modified version of the SMN protein that is deficient in people with spinal muscular atrophy (SMA), was more effective than normal SMN when delivered by gene therapy, a mouse study demonstrated.

Treatment with lower doses of the modified SMN gene therapy, to reduce liver-related toxicity seen with current gene therapies, was still more effective than normal SMN.

[SMN-K186R] has value as a new treatment for SMA that improves treatment effectiveness and reduces adverse events simultaneously, the scientists wrote.

The study, Improved therapeutic approach for spinal muscular atrophy via ubiquitination-resistant survival motor neuron variant, was published in the Journal of Cachexia, Sarcopenia and Muscle.

SMA is caused by defects in the SMN1 gene, which leads to a deficiency in the SMN protein. A lack of SMN mainly affects motor neurons, the specialized nerve cells that control movement, resulting in muscle weakness and atrophy (shrinkage) over time.

Zolgensma (onasemnogene abeparvovec-xioi) is a gene therapy widely approved for newborns and toddlers up to age 2 with all types of SMA. Delivered to cells using a modified and harmless adeno-associated virus serotype 9 (AAV9), the therapy is designed to replace the faulty SMN1 gene and increase the levels of SMN protein.

Although clinical trials have shown that Zolgensma can improve motor skills and extend survival, some patients still fail to achieve motor milestones despite treatment before symptom onset. Moreover, in clinical trials some patients showed liver toxicity due to high AAV9 dosage, even after treatment with immunosuppressants.

Therefore, drug development for an improved therapeutic effect for SMA patients is still needed, the scientists wrote.

In cells, proteins are routinely produced and then degraded in an ongoing dynamic process, depending on cellular needs. Proteins targeted for degradation are tagged with a small protein called ubiquitin, a process called ubiquitination.

In previous work, the research team created a mutant version of the SMN protein, called SMN-K186R, that was resistant to ubiquitination but still retained its function in motor neurons. As a result, the levels of SMN-K186R were sustained for longer periods compared with normal SMN (SMN-WT).

Researchers have now developed an AAV9-based gene therapy, similar to Zolgensma, that delivers the genetic instructions for SMN-K186R to cells and tested its efficacy in a mouse model of severe SMA.

Control SMA mice treated with a mock therapy had an average lifespan of 14 days and survived about four weeks following treatment with SMN-WT. In contrast, mice given SMN-K186R lived an average of 164 days, representing an average lifespan extension of more than 140 days, about 10 times longer than without treatment.

Body weights paralleled the survival results. Untreated mice, or those treated with SMN-WT, initially gained weight and then lost weight until death, whereas mice given SMN-K186R gained weight and size comparable to healthy mice.

Tissue analysis found higher levels of SMN protein in the brain, spinal cord, and muscles in SMA mice treated with SMN-K186R compared with SMN-WT, a result related to ubiquitination resistance. Higher SMN levels due to SMN-K186R coincided with more motor neurons in the spinal cord, greater muscle mass, and thicker muscle fibers.

Several motor function tests showed the improved efficacy of SMN-K186R over SMN-WT. In response to gravity, mice treated with SMN-K186R turned their bodies upward successfully, unlike SMN-WT-treated mice, which failed to turn upwards beyond day 23. Hind-limb clasping upon tail suspension occurs in mice with motor deficits: whereas mice treated with SMN-K186R rarely showed this behavior, SMN-WT-treated mice displayed hind-limb clasping for more than 20 out of 30 seconds.

Due to the potential of treatment-related liver failure (hepatotoxicity) associated with gene therapy, the team examined the effects of SMN-K186R on the liver. By day 25, the average liver weight of mice treated with SMN-K186R was within the normal range, whereas SMN-WT-treated mice had significantly lighter livers.

While the number of liver cells was similar between the two groups, only mice treated with SMN-K186R showed liver cell growth comparable to that of healthy mice. Moreover, liver cells from SMN-WT-treated mice showed signs of SMN protein aggregation, which has been reported to cause defects in motor neurons.

When the dose of SMN-K186R was lowered to one-third of the clinical viral dose to reduce liver toxicity, SMN-WT-treated mice displayed hind-limb clasping, whereas mice treated with the lower dose of SMN-K186R showed no signs of motor deficits.

The higher stability and levels of SMN-K186R generated over SMN-WT did not cause neurotoxicity in the brain and spinal cord or showed early signs of neurotoxicity when delivered directly into the bloodstream.

Our research suggests that an improved therapeutic approach for SMA via ubiquitination-resistant SMN, [SMN-K186R], will achieve better therapeutic effects in severe SMA newborn patients, the scientists wrote. The enablement of low AAV dose treatment from the improved treatment effects of [SMN-K186R] provides strong foundations for clinical applications in SMA patients to reduce hepatotoxicity.

Read more here:
Modified SMN protein aids gene therapy efficacy: Mouse study - SMA News Today

Electrical engineering PhD student Yizhou Yao had to develop a whole new set of skills to research the effects of electric pulses on the receptivity of liver cells to new types of gene therapy. Photo by Joel Hallberg

In an effort to improve delivery of costly medical treatments, a team of researchers in electrical engineering at the University of WisconsinMadison has developed a stimulating method that could make the human body more receptive to certain gene therapies.

The researchers exposed liver cells to short electric pulses and those gentle zaps caused the liver cells to take in more than 40 times the amount of gene therapy material compared to cells that were not exposed to pulsed electric fields. The method could help reduce the dosage needed for these treatments, making them much safer and more affordable. The research appears April 30 in the journal PLOS ONE.

Gene therapy is a promising medical technology: By replacing, altering or introducing new genetic material into a patients cells, doctors may be able to cure or compensate for genetic diseases, including cystic fibrosis, sickle-cell disease, hemophilia and diabetes.

One of the bottlenecks in gene therapy, however, is getting the right dose of genetic material into the target cells. The UWMadison research suggests that applying a moderate electric field, which left no lasting damage to the cells that received it, could help in creating more effective therapies.

The project began almost a decade ago with Hans Sollinger, a world-renowned transplant surgeon at UWMadison. He had developed a gene therapy treatment for Type 1 diabetes, an autoimmune disease that attacks the pancreas, the organ that produces insulin.

From left, Professor John Booske, PhD student Yizhou Yao and Professor Susan Hagness, all in the UWMadison Department of Electrical and Computer Engineering. Photo by Joel Hallberg

Sollingers treatment strategy delivered the genetic code for insulin production into liver cells using an adreno-associated virus that assists in transporting the therapeutic genes across the cells membrane. This DNA can then take up residence in liver cells, producing insulin without being attacked by the immune system in the pancreas.

While Sollinger had a proof of concept that the therapy worked, he believed the future of the treatment hinged on delivery. He turned to Susan Hagness and John Booske, both UWMadison professors of electrical and computer engineering who have experience treating human cells with electrical pulses.

What we started talking about was local, targeted delivery and whether there was a way of getting the treatment DNA directly into the liver without passing it through the entire body and triggering the immune system, says Hagness. And whether we could use electric pulses in order to make this delivery process more efficient and dramatically reduce the dose needed.

Researchers have previously found that exposing cells to electric fields can often increase the ability of molecules to move through the cell membrane into the interior of a cell. So, in this latest study, PhD student Yizhou Yao sought to determine whether the technique would increase the penetration of virus particles into liver cells.

Using human hepatoma cells, a model system for studying the liver, Yao exposed batches of the cells to various concentrations of the gene therapy virus particles containing a fluorescent green protein. She used a pair of electrodes to deliver an 80-millisecond electric pulse to some samples, then incubated all the cells for 12 hours.

When she examined the results 48 hours later under a fluorescence microscope, Yao found that only a small percentage of the cells that had not received the electrical pulses glowed green. In stark contrast, those cells that had received a zap accumulated about 40 times the amount of the fluorescent green proteins delivered by the virus.

While results provided compelling evidence that the pulses helped facilitate the viruss penetration of the cell walls, Booske says the team has yet to discover exactly how the process works at the molecular level.

Theres enough known about electric pulsing that I think we could confidently state that it is opening nanopores through the cell membrane, he says. But then Yao got this remarkable result, and it dawned on us that virus particles are in general bigger and more complex than bare molecular particles and they already have their own way of getting inside cells. So, we dont really know if its the pores opening that has anything to do with it directly or indirectly.

Sollinger passed away in May 2023, but the team says his legacy will live on through the ongoing research on this project and the work of other groups. The electrical engineering researchers are pursuing next steps with external funding and are optimistic that ultimately the technique will translate into clinical trials.

Yao, who will graduate in 2024, says she knew the study would be transdisciplinary, but didnt realize just how far it would go.

I am an electrical engineer by training, and I dont have a biology background, she says. Before this, the last time I used a microscope was in high school. It was quite a steep learning curve, learning to culture cells and carry out biology protocols. But I really enjoyed this project and liked its ultimate goal, which is to make the world a better place.

Other authors include Robert W. Holdcraft of the Cincinnati Childrens Hospital Medical Center.

Original post:
An electrifying discovery may help doctors deliver more effective gene therapies - University of Wisconsin-Madison

Summary: Researchers made a significant breakthrough in ALS treatment using a new gene therapy, marking a notable slow in disease progression for a patient with an aggressive form of ALS. The patient, treated since early 2020, has maintained much of their physical and social abilities, exceeding typical life expectancy and functionality projections for their condition.

This therapy targets the SOD1 gene mutation, reducing levels of a harmful protein and stabilizing the patients condition. The findings offer hope for future advancements in ALS treatment and broader applications of gene therapy.

Key Facts:

Source: Umea University

There has been a breakthrough in the research on the disease amyotrophic lateral sclerosis (ALS).

Scientists at Ume University report that the disease progression in a patient with a particularly aggressive form of ALS disease has slowed down considerably with the use of a new gene therapy.

After four years on the medication, the patient can still climb stairs, rise from his chair, eat and speak well, and live an active and socially fulfilling life.

I consider this a breakthrough for the research we have conducted for more than 30 years, here at Ume University and University Hospital of Northern Sweden. We have never before seen treatment results as effective as these, using any other treatment, says Peter Andersen, a neurologist and professor at the Department of Clinical Sciences at Ume University.

An important discovery is that it is now possible to considerably reduce the levels of the disease-causing SOD1 protein, and simultaneously measure a clear inhibitory effect on furtherdisease progression.

When we diagnosed the patient at the neurology ward inearly spring2020, the patients prognosis was 1.52 years of survival at best. The patient has far, far exceeded expectation.

The patient is from a family in southern Sweden with a particularly aggressive form of ALS disease caused by a mutation in the SOD1 gene. When a relative was diagnosed with ALS, the patient left ablood samplefor research purposes to the ALS research team at Ume University but chose to not learn about the results of the genetic test.

However, the patient was a carrier of the disease gene, and after experiencing muscle weakness four years ago, the patient realized that he too was afflicted. The patient was immediately received by the medical team at University Hospital of Northern Sweden and was diagnosed with early stage ALS disease.

Since the summer of 2020, the patient has been a participant in the Phase III study evaluating a new gene therapy developed for patients with SOD1 mutations causing misfolding and aggregation of SOD1 protein in motorneurons.

Every four weeks, the patient received theexperimental treatmentat a university hospital in Copenhagen in Denmark.

At the time of diagnosis in 2020, the patients levels of the substance neurofilament La biomarker indicating breakdown of nerve cellswas very high. Now, four years later, the levels are reduced by almost 90%.

When the patient was diagnosed at University Hospital of Northern Sweden in April 2020, we measured the level of neurofilament L to be as high as 11,000 nanograms per liter, which is high even for an ALS patient.

In the most recent sample, after 50 injections of the new drug, the level is down to 1,200 to 1,290, which is a substantial decrease of the disease indicator, says Peter Andersen.

The normal level for a person in the patients age group is below 560. In blood, the level of neurofilament has fallen back to normal levels, and was down to 12 during the latest hospital visit. The normal level is less than 13.

The patients level of function, measured using the scale ALSFRSR, is reduced compared to a healthy individual (48 points) but has stayed at almost the same level, around 35 to 37 points, for the last 18 monthsthat means that the patients functional level is reduced by approximately 26% compared to a healthy individual.

A person with this aggressive type of ALS gene mutation that the patient has typically loses 11.5 points every month. That means that without treatment, the expected disease progression would have been very fast and given rise to substantial disability within 612 months, and, most likely, have lead to the patients death in 2021.

That this patient, more or less unimpeded, still can climb stairs four years after disease onset, that is somewhat of a miracle to see, says Karin Forsberg, a neurologist and researcher at the Department of Clinical Sciences who works alongside Peter Andersen and has researched SOD1 and ALS for more than two decades.

To have succeeded with adrug treatmentin this way is a great success and an inspiration. But it does not in any way mean that the job is done. This is just the beginning.

It is also important to remember that the drug in question does not constitute a curative treatment, but it seems able to put the brake on disease progression. It gives us great hope to further develop pharmaceutical treatments for ALS-patients.

There are many types of ALS disease, and only 2% to 6% has an ALS disease caused by a mutation in the SOD1 gene. Many have a familial form of the disease, but mutations in SOD1 have also been found in so-called sporadic cases of ALS.

Whether this drug has a similar effect on other types of ALS disease is currently unknown. There is need for much more research on the subject, says Peter Andersen.

The patient can still do almost all things that he could do when he first joined the study in the summer of 2020his speech is unaffected, and he manages to do everything himself, he mows the lawn, goes shopping, and takes care of his children. Mentally he also feels a lot better, mainly because he now dares to feel hope.

The study that the patient is participating in ends this summer. The medication is not yet available in Sweden, but it has been approved by the United States Food and Drug Administration, FDA, and on the 23 of February 2024 the European Medicines Agency, EMA, recommended the use of the drug on patients with SOD1 gene mutations within the European Union.

However, the New Therapies Council i Sweden has asked the regional health care providers not to prescribe the drug until a health economic evaluation has been provided by the Dental and Pharmaceutical Benefits Agency.

Our next step is to study the results from the patients receiving this drug. It has worked for some, but not all have seen the same positive effect. It could be a question of dosage, or at which disease stage the treatment was initiated.

Maybe additional drugs are required to completely stop the process? Those are questions we now have to try and answer. This is only the beginning, says Karin Forsberg.

She pictures a future where treatment will be given based on what type of ALS disease the patient has, and that it most likely will require a combination of drugs.

She emphasizes that there is much research being conducted both in Sweden and internationally to find new drug targets so that equivalent drugs can be developed for patient groups with other types of ALS, and she is hopeful that it will come true.

We can measure in samples collected from the patient that the disease process is ongoing, but the patients body seems able to compensate. Even now, four years after the patient started taking this new gene therapy drug.

The Swedish Ethical Review Authority approved participation in these studies and now, several years later, we, as well as ALS physicians in other participating countries, see a clear clinical effect on many treated patients, says Peter Andersen.

The next step will be to get approval from the Swedish Ethical Review Authority to study the compensatory mechanisms that treatment with this drug seems to have activated. There might be an opportunity here to get insights into how previously unknown parts of the nervous system work, and to develop even better new drugs.

Author: Peter Andersen Source: Umea University Contact: Peter Andersen Umea University Image: The image is credited to Neuroscience News

Original Research: The findings will appear in eLife.

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Gene Therapy Slows ALS Progression - Neuroscience News

LONDON In 2021, a team of Italian researchers reported that an experimental gene therapy they had developed seemed to be correcting the metabolic issues at the core of a rare genetic disease that left children unable to break down sugar molecules.

There remained an open question, however, about whether the therapy could address a particularly debilitating manifestation of the disease, the severe skeletal deformities it caused. Patients with the disease, called Hurler syndrome, suffer from short stature, spinal defects, and extremely stiff joints, complications that greatly limit their quality of life.

But in a new paper, the research team showed that the gene therapy, when delivered to toddlers, successfully staved off those problems for years. The children grew to heights within average norms, and had far more flexible shoulder, hip, and knee joints than untreated children, according to the study, published Wednesday in the journal Science Translational Medicine. Defects in the patients spines also stabilized.

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Experimental gene therapy seems to alleviate skeletal defects tied to rare inherited disease, study shows - STAT

Poseida Therapeutics and Astellas, under its Xyphos Biosciences subsidiary, have initiated a research collaboration and licensing agreement to develop allogeneic cell therapy programs by combining their innovative cell therapy platforms and technologies.

The companies plan to combine Poseida's proprietary allogeneic chimeric antigen receptor T-cell (CAR-T) platform with Xyphos' Accel platform (which combines its convertibleCAR and proprietary MicAbodies to target tumor cells) to create a Poseida-developed CAR-T construct. This CAR-T construct will then be used to develop two convertibleCAR product candidates targeting solid tumors.

Under the terms of the agreement, Poseida will receive $50 million upfront, plus potential development and sales milestones and contingency payments of up to $550 million in total. Additionally, Poseida is eligible for royalties as a percentage of net sales.

Xyphos will reimburse Poseida for costs incurred as part of the research agreement and will be responsible for the development and future commercialization of the products generated from the collaboration.

In August 2023, Astellas invested $25 million for an 8.8% stake in Poseida and paid an additional $25 million for the right to exclusive negotiation and first refusal to license Poseidas P-MUC1C-ALLO1 CAR-T cell therapy product candidate.

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Astellas and Poseida to collaborate on oncology cell therapies - LabPulse

SOLANA BEACH, Calif., May 02, 2024 (GLOBE NEWSWIRE) -- ClearPoint Neuro, Inc. (Nasdaq: CLPT) (the Company), a global device, cell, and gene therapy-enabling company offering precise navigation to the brain and spine, today announced it will present novel research and exhibit at the 27th American Society of Gene & Cell Therapy Annual Meeting to be held in Baltimore, MD from May 7-11.

The following original research abstracts will be presented at the Poster Session:

Additionally, the Companys technology will be featured in multiple partner posters and presentations. Conference attendees may visit the ClearPoint Neuro booth, #1033, to obtain a comprehensive list. Attendees may also pre-book meetings with our team directly here.

The ASGCT Annual Meeting provides an extraordinary opportunity for us to connect with our existing partners, and attract potential new customers, stated Jeremy Stigall, Chief Business Officer at ClearPoint Neuro. This year, in addition to the posters listed above, there are more than 10 partner-authored abstracts that are enabled by ClearPoint Neuro innovations.

About ClearPoint Neuro

ClearPoint Neuro is a device, cell, and gene therapy-enabling company offering precise navigation to the brain and spine. The Company uniquely provides both established clinical products as well as pre-clinical development services for controlled drug and device delivery. The Companys flagship product, the ClearPoint Neuro Navigation System, has FDA clearance and is CE-marked. ClearPoint Neuro is engaged with healthcare and research centers in North America, Europe, Asia, and South America. The Company is also partnered with the most innovative pharmaceutical/biotech companies, academic centers, and contract research organizations, providing solutions for direct CNS delivery of therapeutics in pre-clinical studies and clinical trials worldwide. To date, thousands of procedures have been performed and supported by the Companys field-based clinical specialist team, which offers support and services to our customers and partners worldwide. For more information, please visit http://www.clearpointneuro.com.

Forward-Looking Statements

This press release contains forward-looking statements within the context of the federal securities laws, which may include the Companys expectations for the future performance, market, and revenue of its products and services. These forward-looking statements are based on managements current expectations and are subject to the risks inherent in the business, which may cause the Company's actual results to differ materially from those expressed in or implied by forward-looking statements. Particular uncertainties and risks include those relating to: global and political instability, supply chain disruptions, labor shortages, and macroeconomic and inflationary conditions; future revenue from sales of the Companys products and services; the Companys ability to market, commercialize and achieve broader market acceptance for new products and services offered by the Company; the ability of our biologics and drug delivery partners to achieve commercial success, including their use of the Companys products and services in their delivery of therapies; the Companys expectations, projections and estimates regarding expenses, future revenue, capital requirements, and the availability of and the need for additional financing; the Companys ability to obtain additional funding to support its research and development programs; the ability of the Company to manage the growth of its business; the Companys ability to attract and retain its key employees; and risks inherent in the research, development, and regulatory approval of new products. More detailed information on these and additional factors that could affect the Companys actual results are described in the Risk Factors section of the Companys Annual Report on Form 10-K for the year ended December 31, 2023, which has been filed with the Securities and Exchange Commission, and the Companys Quarterly Report on Form 10-Q for the three months ended March 31, 2024, which the Company intends to file with the Securities and Exchange Commission on or before May 15, 2024. The Company does not assume any obligation to update these forward-looking statements.

Excerpt from:
ClearPoint Neuro to Present Novel Research and Exhibit at the 27th American Society of Gene & Cell Therapy Annual ... - GlobeNewswire

Research Triangle Park, N.C., May 02, 2024 (GLOBE NEWSWIRE) -- Asklepios BioPharmaceutical, Inc. (AskBio), a gene therapy company wholly owned and independently operated as a subsidiary of Bayer AG, will deliver nine presentations offering insights into its adeno-associated virus (AAV) research and development, a key area of gene therapy focus for the company, at the American Society of Gene and Cell Therapy (ASGCT) 27th Annual Meeting, which takes place May 711, 2024, in Baltimore, Maryland, USA. Presentations will focus on AAV immune-mediated responses as well as the results from the ongoing Phase 1 clinical trial of AB-1002 gene therapy in patients with advanced heart failure.

Luke Roberts, MBBS, PhD, Medical Director for Clinical Development at AskBio, will deliver an oral presentation sharing new clinical data from the companys ongoing Phase 1 trial of AB-1002 in patients with advanced heart failure. This follows AskBios recent news that AB-1002 was granted FDA Fast Track Designation for the treatment of congestive heart failure (CHF). AB-1002 (also known as NAN-101) is an investigational gene therapy that has not yet received marketing authorization, and its efficacy and safety have not been established or fully evaluated. AskBio previously communicated that the delivery of AB-1002 was well tolerated and resulted in positive preliminary efficacy outcomes in some patients with non-ischemic CHF and may validate that the AAV2i8 vector capsid used is highly cardiotropic when administered as a single intracoronary infusion at relatively low doses.

Preliminary data from the Phase 1 trial of AB-1002 were presented at the 2023 American Heart Association Scientific Sessions in November, and AskBio began enrolling patients in its Phase 2 GenePHIT study of AB-1002 in adults with non-ischemic cardiomyopathy and New York Heart Association (NYHA) Class III heart failure symptoms in January 2024.

AskBios ASGCT presence will also include key presentations showcasing the companys continued commitment to optimizing AAV as a gene therapy, with a focus on preventing or reducing AAV immune response-related adverse events, which remains a vital area of investigation across the gene therapy treatment landscape. Attendees can look forward to an ASGCT spotlight speaker presentation on current immune modulation strategies given by Shari Gordon, PhD, Senior Director of Immunology at AskBio, on Day 3. On Day 4, Shari Gordon will deliver on behalf of Audry Fernandez, PhD, Principal Scientist & Group Lead, Immunology R&D at AskBio, an oral presentation on pre-clinical research into AAV-specific immune responses, and Liujiang Song, PhD, Principal Scientist for R&D Capsid and Biology at AskBio, will offer insights into AAV biology and vector intracellular fate during an oral presentation on AAV episome configuration using third generation long-read sequencing technologies and advanced bioinformatics.

Our presence at ASGCT this year highlights our continued commitment to sharing AAV developments with the gene therapy community. Covering clinical and pre-clinical research, our presentations show our robust progress and ongoing ambition to bring to patients transformative therapies that were once unthinkable, said Gustavo Pesquin, Chief Executive Officer, AskBio. With our clinical and early-stage programs advancing, these are exciting times at AskBio.

With an ambitious portfolio of gene therapies at various stages of research and development, AskBio continues to develop AAV-based therapies to treat some the worlds most debilitating diseases, including CHF, Huntingtons disease, limb-girdle muscular dystrophy, multiple system atrophy, Parkinsons disease, and Pompe disease. By targeting these therapy areas, AskBio aims to deliver breakthrough treatments that could benefit more than an estimated 35 million patients worldwide.17

AskBios presentations at ASGCT include:

About AskBio

Asklepios BioPharmaceutical, Inc. (AskBio), a wholly owned and independently operated subsidiary of Bayer AG, is a fully integrated gene therapy company dedicated to developing life-saving medicines and changing lives. The company maintains a portfolio of clinical programs across a range of neuromuscular, central nervous system, cardiovascular, and metabolic disease indications with a clinical-stage pipeline that includes therapeutics for congestive heart failure, Huntingtons disease, limb-girdle muscular dystrophy, multiple system atrophy, Parkinsons disease, and Pompe disease. AskBios gene therapy platform includes Pro10, an industry-leading proprietary cell line manufacturing process, and an extensive capsid and promoter library. With global headquarters in Research Triangle Park, North Carolina, and European headquarters in Edinburgh, Scotland, the company has generated hundreds of proprietary capsids and promoters, several of which have entered pre-clinical and clinical testing. An early innovator in the gene therapy field, with over 900 employees in five countries, the company holds more than 800 patents and patent applications in areas such as AAV production and chimeric capsids. Learn more at http://www.askbio.com or follow us on LinkedIn.

About Bayer

Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. In line with its mission, Health for all, Hunger for none, the companys products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2023, the Group employed around 100,000 people and had sales of 47.6 billion euros. R&D expenses before special items amounted to 5.8 billion euros. For more information, go towww.bayer.com.

About Viralgen Vector Core

Viralgen is a Contract Development and Manufacturing Organization (CDMO) founded in 2017 and exists as an independently operated subsidiary of AskBio, which is wholly owned and independently operated as a subsidiary of Bayer AG. As a manufacturer of Current Good Manufacturing Practice (cGMP) certified AAV, Viralgen offers the Pro10 based suspension manufacturing platform, a technology licensed from AskBio and developed by Chief Technical Officer Josh Grieger, PhD, and Co-Founder R. Jude Samulski, PhD, at University of North Carolina. The Pro10 platform has been found to increase scalability, performance, and yield of AAV therapies.8 Located in Spain, in the Gipuzkoa Science and Technology Park, Viralgen produces AAV gene therapy treatments for pharmaceutical and biotech companies with the aim of accelerating the delivery of new treatments that may improve patients lives.

The companys clinical facilities have four cGMP manufacturing suites, with 250-liter and 500-liter bioreactors. In 2020, Viralgen expanded within the Scientific Park by constructing a new building with three modules for large-scale commercial manufacturing. Each module of the state-of-the-art space includes three cGMP suites with a manufacturing capacity of >2,000 liters. The first module, which includes a suite dedicated to fully automated fill and finish operations, has received cGMP certification by the Spanish Agency for Medicines and Medical Devices (AEMPS) as part of the EMA network. For more information, visit viralgenvc.com.

Bayer Forward-Looking Statements

This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayers public reports which are available on the Bayer website atwww.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

AskBio Forward-Looking Statements

This press release contains forward-looking statements. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Words such as believes, anticipates, plans, expects, will, intends, potential, possible, and similar expressions are intended to identify forward-looking statements. These forward-looking statements include, without limitation, statements regarding AskBios clinical trials. These forward-looking statements involve risks and uncertainties, many of which are beyond AskBios control. Known risks include, among others: AskBio may not be able to execute on its business plans and goals, including meeting its expected or planned clinical and regulatory milestones and timelines, its reliance on third-parties, clinical development plans, manufacturing processes and plans, and bringing its product candidates to market, due to a variety of reasons, including possible limitations of company financial and other resources, manufacturing limitations that may not be anticipated or resolved in a timely manner, potential disagreements or other issues with our third-party collaborators and partners, and regulatory, court or agency feedback or decisions, such as feedback and decisions from the United States Food and Drug Administration or the United States Patent and Trademark Office. Any of the foregoing risks could materially and adversely affect AskBios business and results of operations. You should not place undue reliance on the forward-looking statements contained in this press release. AskBio does not undertake any obligation to publicly update its forward-looking statements based on events or circumstances after the date hereof.

References

[1] Balestrino R, Schapira AHV. Parkinson disease. Eur J Neurol. 2020;27(1):27-42.

[2] World Health Organization. Parkinson Disease. Available at:https://www.who.int/news-room/fact-sheets/detail/parkinson-disease. Accessed April 2024.

[3] Medina A, et al. Prevalence and Incidence of Huntington's Disease: An Updated Systematic Review and Meta-Analysis. Mov Disord. 2022;37(12):2327-2335.

[4] Malik A, et al. Congestive Heart Failure. In: StatPearls. Treasure Island (FL): StatPearls Publishing; November 7, 2022.

[5] MedlinePlus Genetics. NIH. Limb-girdle muscular dystrophy. Available at:https://medlineplus.gov/genetics/condition/limb-girdle-muscular-dystrophy/#frequency. Accessed April 2024.

[6] Goh Y, et al. Multiple system atrophy [published online ahead of print, 2023 Mar 16]. Pract Neurol. 2023; practneurol-2020-002797.

[7] Stevens D, et al. Pompe Disease: a Clinical, Diagnostic, and Therapeutic Overview. Curr Treat Options Neurol. 2022;24(11):573-588.

[8] Grieger JC, Soltys SM, Samulski RJ. Production of Recombinant Adeno-associated Virus Vectors Using Suspension HEK293 Cells and Continuous Harvest of Vector From the Culture Media for GMP FIX and FLT1 Clinical Vector. Mol Ther. 2016;24(2):287-297.

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AskBio Announces Nine Presentations at American Society of Gene and Cell Therapy 27th Annual Meeting 2024 - GlobeNewswire

San Diego, USA-based clinical-stage cell and gene therapy company Poseida Therapeutics (Nasdaq: PSTX) saw its shares close up more than 20% at $2.92 yesterday, when it revealed a second collaboration with Japanese drug major Astellas Pharma (TYO: 4503).

Astellas wholly-owned Xyphos Bioscience and Poseidahave entered into a research collaboration and license agreement to develop novel convertible CAR programs by combining the innovative cell

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Astellas and Poseida enter second research collaboration - The Pharma Letter

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Genetically engineered B cells could produce super-antibodies to HIV

Researchers at Washington University School of Medicine in St. Louis have received a $6.2 million grant from the National Institutes of Health (NIH) to develop a gene therapy that would modify the immune systems B cells to spur them to produce broadly neutralizing antibodies against HIV. In theory, such an approach could control or eliminate the infection without need for ongoing antiretroviral therapy. Shown is the engineered adenovirus designed to deliver HIV superantibody genes into B cells.

HIV infections can be controlled with medication, but such therapy must continue throughout patients lives because no strategy exists to eliminate the virus from the body or control the infection without ongoing treatment.

With the aim of developing such a strategy, researchers at Washington University School of Medicine in St. Louis have received a $6.2 million grant from the National Institutes of Health (NIH) to develop a gene therapy that would modify the immune systems B cells to spur them to produce broadly neutralizing antibodies against HIV. In theory, such an approach could control or eliminate the infection without need for ongoing antiretroviral therapy.

Permanent ways to control or eliminate HIV infection remain elusive, and their development is a major goal of the field, said David T. Curiel, MD, PhD, the Distinguished Professor of Radiation Oncology. The idea of modifying B cells which naturally produce antibodies to ensure that they manufacture specific antibodies that are broadly effective at targeting HIV is an exciting strategy. We have brought together a great team with expertise in HIV, gene therapy, and animal models of infection to work toward this goal.

Curiels co-principal investigators are Michael R. Farzan, PhD, of Harvard Medical School and Boston Childrens Hospital, and Mauricio de Aguiar Martins, PhD, of the University of Florida.

Over the decades since HIV appeared, researchers have learned that about 1% of people with the virus are able to produce what might be considered superantibodies against the virus. Such individuals known as elite neutralizers can produce antibodies against multiple strains of HIV.

Some people naturally have antibodies that can bind and destroy or deactivate very diverse strains of HIV, and we now have the ability to build those types of antibodies in the lab, said Paul Boucher, a doctoral student in Curiels lab. But just giving other patients these superantibodies is not an ideal solution, because these proteins would stay in the body only temporarily. Instead, our approach is to genetically modify the cells responsible for making antibodies the immune systems B cells so they can always produce superantibodies against HIV whenever they may need to.

Such engineered B cells could create, in theory, a state of permanent vaccination against the virus. Even if such a gene therapy doesnt fully clear HIV from the body, the strategy could allow the amount of virus in the body to be controlled, keeping it at a minimal level and creating a functional cure, according to the researchers.

The strategy involves modifying a different type of virus, called adenovirus. When used in gene therapy, such viruses are genetically disabled so they cant cause disease. The researchers then could engineer the adenovirus to carry the gene responsible for manufacturing broadly neutralizing antibodies to HIV. In the same viral vector, they also could include genes responsible for manufacturing the CRISPR/Cas9 gene editing proteins. In this way, the gene therapy delivery vehicle would carry into the body both the antibody gene that will be edited into the B cell genome and the genes to build the molecular tools to carry out that editing.

Using a three-part targeting strategy, the researchers would design the adenovirus to deliver its genetic payload only to B cells, avoiding other cell types. They have developed ways to modify the virus so that it is targeted directly to a protein that is expressed on the surface of B cells and no other cell types. The researchers can further restrict the targeting by using genetic methods to ensure that the CRISPR/Cas9 proteins can only be manufactured when their genes are delivered into B cells. Finally, they have developed strategies to modify the adenovirus in a way that stops its natural tendency to accumulate in the liver.

This strategy to modify B cells is distinct from another adenoviral gene therapy approach to HIV treatment that is currently in clinical trials led by principal investigator Rachel M. Presti, MD, PhD, a professor of medicine in the Division of Infectious Diseases at Washington University School of Medicine. HIV is difficult to eliminate from the body because the virus integrates its genome into the DNA of the infected individuals T cells. The strategy currently in clinical trials is focused on using precise targeting of the CRISPR/Cas9 gene editing proteins to excise the virus from the genomes of all of a patients infected T cells. This strategy is being tested in a first-in-human, phase 1 clinical trial to determine its safety and preliminary efficacy at various doses.

Curiel said engineered B cells are ripe for developing new therapies to treat a wide variety of diseases. In November, a genetically engineered B cell therapy was administered to a patient for the first time at the University of Minnesota Medical Center. In that case, the therapy was designed to treat mucopolysaccharidosis type 1, a life-threatening condition in which the body lacks an enzyme necessary to break down large sugar molecules inside cells.

Gene therapy with engineered B cells is an exciting new area of research, Curiel said. We look forward to combining our expertise in adenovirus gene therapy, HIV infection and preclinical models of disease to realize our plan for developing an HIV therapy that we hope can permanently control the infection.

This work is supported by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH), grant number 1R01-AI174270-01A1. This content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

About Washington University School of Medicine

WashU Medicine is a global leader in academic medicine, including biomedical research, patient care and educational programs with 2,900 faculty. Its National Institutes of Health (NIH) research funding portfolio is the second largest among U.S. medical schools and has grown 56% in the last seven years. Together with institutional investment, WashU Medicine commits well over $1 billion annually to basic and clinical research innovation and training. Its faculty practice is consistently within the top five in the country, with more than 1,900 faculty physicians practicing at 130 locations and who are also the medical staffs of Barnes-Jewish and St. Louis Childrens hospitals of BJC HealthCare. WashU Medicine has a storied history in MD/PhD training, recently dedicated $100 million to scholarships and curriculum renewal for its medical students, and is home to top-notch training programs in every medical subspecialty as well as physical therapy, occupational therapy, and audiology and communications sciences.

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$6.2 million to help develop gene therapy for HIV Washington University School of Medicine in St. Louis - Washington University School of Medicine in...

A type of gene therapy called CAR-T that has extended survival for thousands of patients with leukemia and other blood cancers is being adapted at UC San Francisco to treat people with glioblastoma, the most common and deadly adult brain tumor.

This new more powerful version of CAR-T employs a novel technology developed at UCSF called synthetic notch (synNotch) that both protects healthy tissue from damage and enables the treatment to work more effectively.

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Approximately 12,000 Americans are diagnosed each year, with an average survival of just 15 months.

UCSF opened enrollment this week for a clinical trial that is using the technology for the first time in people. A second trial, also at UCSF, is slated for 2025.

Approximately 12,000 Americans are diagnosed each year with glioblastoma. Patients survive on average for just 15 months after their diagnosis, and new treatments are urgently needed.

This project is a prime example of bench-to-bed translation within UCSF, representing the strengths in basic and clinical science, said Hideho Okada, MD, PhD, a physician-scientist and director of the UCSF Brain Tumor Immunotherapy Center. We have a truly home-grown project here.

Okada has received up to $11 million for the first trial from the California Institute for Regenerative Medicine (CIRM), which funds stem cell and gene therapy research for incurable diseases and disorders through all stages of clinical trial development.

Initial funding for the second trial is provided by the National Cancer Institute Specialized Programs of Research Excellence (NCI SPORE).

We hope that the treatment will prolong lives for patients with glioblastoma, said Okada, who is a professor of neurosurgery at UCSF and a member of the Weill Institute for Neurosciences. However, the primary goal of the current phase 1 study is to ensure safety and characterize any toxicities.

When tested in mice, Okada said the therapy provided a robust and long-lasting result that was more remarkable than anything he had encountered during 30 years of brain tumor research.

The CIRM-funded trial will be led by principal investigator Jennifer Clarke, MD, MPH. It is open to patients with newly diagnosed glioblastoma, who have completed standard-of-care treatment. Tumors must have a mutation found in approximately 20% of glioblastomas, and that can be identified by the UCSF500 cancer gene panel test.

The second study will be open to glioblastoma patients whether or not they have the mutation.

CAR-T refers to chimeric antigen receptor T-cells, which are cancer-killing immune cells that have been extracted from the patient and genetically modified to recognize and destroy antigens that appear on the surface of cancer cells. These supercharged CAR-T cells are then infused back into the body to attack tumor cells.

For many patients with leukemia and other blood cancers, CAR-T has demonstrated long-term remission, but the approach hasnt worked against brain tumors. Glioblastoma cells are more diverse than blood cancer cells, and they can evade CAR-T. Many of the antigens made by the tumors are also found in healthy tissue, leaving them open to attack.

To overcome these obstacles, Okada drew from the synNotch system developed by Wendell Lim, PhD, director of the UCSF Cell Design Institute and professor in the UCSF Department of Cellular and Molecular Pharmacology.

The technology allowed scientists to program CAR-T cells to target specific antigens on tumor cells, without touching those found in healthy tissue. They also do not succumb to T-cell exhaustion, a common problem with CAR-T therapies, because they are more metabolically stable and use less energy to fight cancer longer.

Weve created a system that is flexible and thorough and addresses the major concerns weve had about using CAR-T cells against solid tumors, Lim said. These cells act like computers: integrating multiple units of information and making complex decisions.

About the California Institute for Regenerative Medicine (CIRM): AtCIRM, we never forget that we were created by the people of California to accelerate stem cell treatments to patients with unmet medical needs, and act with a sense of urgency to succeed in that mission. To meet this challenge, our team of highly trained and experienced professionals actively partners with both academia and industry in a hands-on, entrepreneurial environment to fast track the development of todays most promising stem cell technologies. With $5.5 billion in funding and more than 150 active stem cell programs in our portfolio,CIRMis one of the worlds largest institutions dedicated to helping people by bringing the future of cellular medicine closer to reality.

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Gene Therapy Is Halting Cancer. Can It Work Against Brain Tumors? - UC San Francisco

Gene therapy research is booming. Since the U.S. Food and Drug Administration (FDA) issued its first approval for a gene therapyin 2017, oncology researchers have been breaking barriers in gene therapy trials, followed by an explosion in mRNA research during the COVID pandemic. Today, this trailblazing science is providing new ways to approach rare diseases and new hope when other investigational interventions have failed. In fact, themajorityof approved gene therapies are for rare diseases 14 are currently in Phase III trials for 10 rare diseases and 45 gene therapies are in early stages of development to treat 30 rare diseases. We see great potential for gene therapies, said Leslie Johnston, senior vice president of biotech delivery for Parexel. As more products are approved, it will gain traction and more companies will look to expand their therapies into other therapeutic indications. This progress presents tremendous potential to change more patients lives across many different diseases. This could be gene therapys moment. But to fully seize it, the industry must clear some complex hurdles. Gene therapies pose several unique challenges for clinical research, including ethical and safety considerations, regulatory hurdles, precarious logistics, and potentially staggering costs. These challenges may already be having ramifications: New U.S. patients treated with gene therapies approved or in development areexpected to fallby one-third from 2025 to 2034. The key to clearing these hurdles? Cooperation between sponsors, sites, regulators, patients, and other stakeholders is essential to expediting the advancement of life-saving gene therapies. Regulators should address risks without limiting innovation Gene therapy trials are strictly regulated and rightly so, due to the novel nature of the intervention and the potential long-term consequences. Gene therapy interventions also carry inherent safety risks, including the potential for unintended genetic changes or adverse immune reactions. Ensuring patient safety requires rigorous monitoring and adherence to strict protocols. However, obtaining regulatory approval under these conditions is time consuming and resource intensive. To avoid hampering scientific progress, regulators should aim to ensure that requirements are appropriately rigorous without being unmanageably onerous. Thankfully, the FDA is paying close attention to gene therapy and has demonstrated a desire to work with drug developers toward the success and approval of these treatments. Dr. Peter Marks, Director of the Center for Biologics Evaluation and Research (CBER) at the FDA, has expressed his hope for an exponential, if not logarithmic, increase in gene therapy approvals. There is a lot of excitement that this could potentially make a big difference for the treatment of human disease, said Dr. Marks in hisremarksto the National Press Forum last November. The FDA is going beyond mere rhapsodizing and taking action to accelerate gene therapy. Last year, the agencylaunched a pilot programcalled Support for Clinical Trials Advancing Rare Disease Therapeutics, or START. This program is designed to accelerate the development and approval process for treatments targeting rare diseases by providing regulatory guidance, assistance, and incentives to sponsors conducting clinical trials in this field. The program represents an important step forward in fostering innovation and collaboration between regulatory bodies and sponsors. In addition, the FDA is working toharmonize global requirementsfor the review of gene therapies. Encouraging and facilitating international cooperation and harmonization of regulatory standards including mutual recognition agreements and shared regulatory pathways for multinational clinical trials can help streamline gene therapy development globally and help bring innovations to patients faster. Even with this progress, regulators should continue to help accelerate gene therapy research by streamlining regulatory pathways specifically tailored to gene therapies. This means providing clear guidance on requirements for preclinical and clinical development, fostering collaboration between stakeholders to share knowledge and best practices, and offering expedited review processes for gene therapy products aimed at treating serious or life-threatening diseases. With a staggering2,500 cell and gene therapyinvestigational new drug applications (INDs) on file, the FDA approved justfivecell and gene therapies in 2023. Dr. Marks hassuggestedthat accelerated approval, which has successfully advanced cancer and HIV/AIDS treatments, may be the most appropriate path for this new category of treatments. But, regulators also need to commit to proactively partner with developers to understand the patient population and the risks and benefits of each new therapy. Likewise, researchers, industry stakeholders, and patient advocacy groups should engage with regulators to help them understand the unique challenges and opportunities in the field of gene therapy. This can help regulators adapt regulatory frameworks to ensure patient safety while expediting the development and approval of promising treatments. Sites and sponsors must be prepared Of course, sites and sponsors also have a crucial part to play in advancing this promising field of medicine. Clinical trial sites should enhance their capacity to conduct gene therapy trials safely and effectively and sponsors should do their part to assist sites in these efforts. By working closely with clinicians and regulators, sponsors can ensure that the trial development process aligns with clinical needs and regulatory standards. Sponsors should have a thorough understanding of FDA requirements pertaining to design, preclinical testing, and long-term follow-up. Better alignment from the outset will lead to more efficient trial designs, faster regulatory approvals, and ultimately quicker patient access to therapies. For example, sponsors working with mRNA and other genetically engineered therapies in North America not only have to go through institutional review board (IRB) review, they also have to navigate additional requirements from the U.S. National Institutes of Health (NIH) Office of Science PolicyGuidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules(NIH Guidelines). These requirements usually involve an additional biosafety risk assessment review from an institutional biosafety committee (IBC) in addition to IRB review. NIH Guidelines apply for any research involving recombinant or synthetic nucleic acids (e.g. genetically engineered materials) that receives NIH support or takes place at sites that have received NIH support for such research. Even when there is zero NIH support, IBC review is considered a best practice. IBC review and inspection helps sites ensure they are fully prepared by identifying areas for improved biosafety protections and calling out gaps in current standard operating procedures (SOPs). Proactive coordination and integration of these separate review processes can speed trial timelines and help sponsors consistently address any potential concerns or issues. Sites can also be better prepared by pre-registering an IBC. The NIH takes six to eight weeks or more to approve a new registration, in addition to IBC review time so by registering an IBC before they even have a trial, sites can save a month or more in startup time over a site that waited to register. Clinical trial sites looking to host gene therapy studies must be prepared in other ways, as well, both in terms of knowledge and infrastructure. Gene therapy studies require specialized infrastructure for manufacturing, storing, and administering genetic material to adhere to strict biosafety guidelines. Something as simple as having an upholstered chair in the infusion room which would pose an unacceptable contamination risk if genetic materials were to spill would require the site to rethink their current processes. Rigorous training is also key due to the added risk of spreading genetic material to caregivers and others in close contact with patients. Research staff must be specially trained to handle, deliver, and dispose of this material safely. Of course, these measures can seem intimidating for sites that are already cost-constrained. Large academic medical centers with more resources and experience are more likely to be well-positioned for these studies. For instance, they may already have conducted bench, animal, and/or agricultural research with genetic engineering or have the funding to make any needed adjustments such as purchasing special equipment. But to maximize the potential number of sites where this research can be conducted and therefore reach more potential participants sponsors might consider providing help in the form of financial assistance, training curricula, SOP guidance, and more to smaller sites seeking to conduct gene therapy research. Logistical complexities depending on the investigational medicine and therapeutic area are among the most complicated challenges in gene therapy trials, added Johnston. From collecting the specimen from the patient, modifying it, storing it, transporting it, and then returning it back to the patient all comes with tremendously unique logistical challenges and requires equally unique equipment, technology, and expertise. And it can be cost-prohibitive. Patients must be fully on board Of course, the most essential stakeholder in any clinical trial is the patient. In gene therapy research, which can be particularly demanding, patients must have a complete understanding of and commitment to their involvement. Understanding the potential risks and benefits can help patients make informed decisions and navigate the study process. First, it's crucial for patients to adhere strictly to the protocol provided by the clinical trial team, including following medication schedules, maintaining specific hygiene practices, and attending all study visits. They should strive to maintain optimal health to enhance the body's response to gene therapy. And to avoid delays, patients should maintain open and honest communication with the clinical trial team, reporting any changes in symptoms, side effects, or general health as soon as they occur. Trial participants also need to be in it for the long haul. Because gene therapy interventions aim to produce lasting effects, even cures, they typically require long-term patient follow-up to assess efficacy and safety. But they may also need to have incredible patience. Johnston explained, There are many complexities that can impact study progress. For example, unpredictable logistical challenges like a weather event or vehicle accident could delay a temperature-sensitive delivery to a site, or data review outcomes could require an indeterminate pause period. Patience and agility are must-haves, but it is difficult for patients potentially depending on this new therapy to save or change their lives. Lastly, the industry cannot forget the patient. Involving patients and patient advocacy groups in the regulatory process can help ensure that the development of gene therapies is aligned with patient needs and priorities, as well as shed light on risk-benefit perspectives from a patients viewpoint. The more these perspectives are considered from the beginning, the greater the chance of a trials success. Rita Naman, co-founder of the Mighty Milo Foundation, emphasizes the need for a more collaborative and patient-centered approach to gene therapy development. "For ultra-rare diseases likeSPAX5, gene therapy offers a glimmer of hope where traditional treatments do not. But logistical hurdles make these therapies expensive and inaccessible, explained Naman. Closer collaboration with patients, industry, and regulators could streamline these processes, drive costs down, and speed trials. Patients like my son, and their caregivers, plus advocacy groups should be invited into the earliest discussions to prevent false starts or missed milestones in gene therapy development especially as the patients priorities dont always line up with the sponsors. In the fight for gene therapy breakthroughs, cooperation is key. The road to operationalizing gene therapy clinical trials is laced with land mines and potholes. To capture the full potential of novel gene therapy research, a new level of collaboration between sponsors, CROs, sites, oversight committees, regulatory bodies, and patients is paramount. Patients want access to novel gene treatments, and they want it fast. Sponsors want to deliver but fight logistical and financial obstacles. Regulators want to ensure safety first, especially considering such new, promising science, concluded Johnston. These three goals may seem conflicting at times, so we need to strike a balance of safety and speed, so patients dont miss their only potential treatment opportunity. A seasoned industry veteran with more than 25 years of experience, James Riddle is senior vice president of global review operations at Advarra. Riddles expertise includes large program management and growth, operational processes, development and implementation of technology solutions, and management of large Human Research Protection Programs (HRPP), Biosafety programs (IBC) and Institutional Animal Care and Use programs (IACUC). Riddle has directed numerous clients in achieving Part 11 compliance and meeting computer system validation requirements.

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Gene Therapy is Having its Moment: Can the Clinical Research Ecosystem Seize It? - Contract Pharma

One of their biggest successes uses gene therapy to treat a rare genetic disorder called aromatic L-amino acid decarboxylase (AADC) deficiency.

Children with AADC deficient are missing the enzyme that produces dopamine and serotonin in the central nervous system. This affects pathways in the brain responsible for motor function and emotions.

As a result, these children cant coordinate the movements of their head, face and neck. They often dont reach normal childhood milestones, such as sitting up or walking by themselves.

Along with her mother, Arcelia Ramirez, they traveled 800 miles from their home near Omaha, Neb., so that Delilah could have this life-changing gene therapy surgery at Ohio State Wexner Medical Center.

But now, Delilah has changed so much for the better. On her 9th birthday, she blew out a candle on her cupcake on purpose. This was the first time she had ever blown out a birthday candle.

She's like a different kid. Her sleeping is a lot better. She can walk now, she can self-feed, said Arcelia Ramirez. When she started using a fork, that was a reason to celebrate. When she started using a straw, that was a reason to celebrate. Walking was a big, big milestone for her that we just celebrated.

So we are bringing in a correctly spelled sequence of the gene, said Bankiewicz, who is also chief scientific officer at the Ohio State Gene Therapy Institute.

This helps ensure we put the genetic material in exactly the right place, so the brain will start making dopamine and serotonin again, said Elder, who also is a professor of neurological surgery. This

therapy is designed to approach both parts of the brain that control movements and emotions.

This breakthrough in treating patients with AADC was decades in the making.

It requires a use of the technology and devices that we had to develop and establish over the years to do these surgeries very precisely, very carefully and then do it safely, Bankiewicz said. The issue of, Is it going to work? It's no longer being questioned. It works.

In addition to expanding this method to central nervous system diseases such as Alzheimers, Parkinsons, Multiple System Atrophy and Huntingtons disease, Elder and Bankiewicz are also trying to edit genetic mutations in other neurological disorders, including brain tumors.

We are not treating a gene that causes Parkinson's or Alzheimer's, Bankiewicz said. We're using this technology to deliver a therapeutic that we believe will, in a positive way, affect the progression of the disease.

# # #

Media Contact: Eileen Scahill, Wexner Medical Center Media Relations, Eileen.Scahill@osumc.edu

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The future of gene therapy has arrived, and it's changing lives - Wexner Medical Center - The Ohio State University

The global gene therapy market size was valued at USD 8.75 billion in 2023 and is poised to grow from USD 10.47 billion in 2024 to USD 52.40 billion by 2033, growing at a CAGR of 19.6% in the forecast period (2024-2033).

Gene therapy is a technique that uses a gene to treat, prevent or cure a disease or medical disorder. Often, gene therapy works by adding new copies of a gene that is broken, or by replacing a defective or missing gene in a patients cells with a healthy version of that gene. Both inherited genetic diseases (e.g., hemophilia and sickle cell disease) and acquired disorders (e.g., leukemia) have been treated with gene therapy.

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The development of the market is owing to an increase in the number of gene therapy-based discoveries, increasing investment in this sector, and rising approval of gene therapy products. According to the WHO, 10 to 20 new cell and gene therapies are expected to be approved each year by 2025.

Continuous developments in recombinant DNA technology are anticipated to enhance the efficiency of gene therapy in the coming years. Hence, ongoing progresses in recombinant DNA technology are anticipated to expand the number of ongoing clinical trials for gene therapy. Primarily, these advancements are taking place in the context of various gene-editing tools and expression systems to augment the R&D for products. The advent of CRISPR/Cas9 nuclease, ZFN, and TALEN allows easy & precise genome editing. As a result, in recent times, the gene-editing space has witnessed a substantial number of research activities, which, in turn, is expected to influence the growth of the gene therapy market.

The growth of the gene therapy market is expected to be majorly benefitted from the increasing prevalence of cancer. The ongoing increase in cancer patients and related death per year emphasizes the essential for the development of robust treatment solutions. In 2020, there were around 18.1 million new cases of cancer worldwide. 9.3 million of these cases involved men, while 8.8 million involved women. Continuing developments in tumor genetic studies have delivered substantial information about cancer-related molecular signatures, which in turn, is expected to support ongoing clinical trials for cancer therapeutics.

With rising demand for robust disease treatment therapies, companies have focused their efforts to accelerate R&D for effective genetic therapies that target the cause of disease at a genomic level. . Furthermore, the U.S. FDA provides constant support for innovations in this sector via a number of policies with regard to product manufacturing. In January 2020, the agency released six final guidelines on the manufacturing and clinical development of safe and efficient products.

Furthermore, facility expansion for cell and gene therapies is one of the major factors driving the gene therapy market growth. Several in-house facilities and CDMOs for gene therapy manufacturing have begun investing to enhance their production capacity, which, in turn, is anticipated to create lucrative opportunities for market players. For instance, in April 2022, the FDA approved commercial licensure approval to Novartis for its Durham, N.C. site. This approval permits the 170,000 square-foot facility to make, test, and issue commercial Zolgensma, as well as manufacture therapy products for current & upcoming clinical trials.

Cell and Gene Therapy Market :https://www.biospace.com/article/releases/u-s-cell-and-gene-therapy-clinical-trial-services-industry-is-rising-rapidly/

Gene Therapy Market Report Highlights

U.S. Gene Therapy Market Size in U.S. 2024 to 2033

The U.S. gene therapy market size was estimated at USD 3.19 billion in 2023 and is projected to surpass around USD 18.50 billion by 2033 at a CAGR of 19.22 % from 2024 to 2033.

North America dominated the market in 2023 with the largest revenue share of 65.12% in 2023. This region is expected to become the largest routine manufacturer of gene therapy in terms of the number of approvals and revenue generated during the forecast period. Increasing investments in R&D from large and small companies in the development of ideal therapy drugs are anticipated to further boost the market.

Furthermore, the increasing number of investments by the governments and the growing prevalence of targeted diseases are the factors fueling the market. According to the Spinal Muscular Atrophy Foundation, in 2020, around 10,000 to 25,000 children and adults in the U.S. were affected by spinal muscular atrophy, making it a fairly common disease among rare diseases.

Europe is estimated to be the fastest-growing regional segment from 2024 to 2030. This is attributed to its large population with unmet medical needs and increasing demand for novel technologies in the treatment of rare but increasingly prevalent diseases. Asia Pacific market for commercial application of genetic therapies is anticipated to witness significant growth in the forecast period, which can be attributed to the easy availability of resources, local presence of major companies, and increased investment, by the governments.

UK Gene Therapy Market

The UK gene therapy market is anticipated to witness accelerated growth over the forecast period, due to increased investments by various big companies and governments, including the NHS & research laboratories. For instance, in March 2022, the UK government invested USD 326.45 million to accelerate healthcare research and manufacturing. Under this investment, additional $80 million of the fund will help companies at the forefront of invention with their commercial-scale manufacturing investments in areas like gene and cell therapies, as well as improved diagnostic technologies, among others. Various mergers & partnerships between manufacturers, universities, and other government bodies are expected to boost the market over the forecast period.

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What is gene therapy used for?

Most gene therapies are still in the clinical trial phase. Clinical trials play an important role in finding treatments that are safe and effective. Clinical trials are investigating gene therapy for the treatment ofcancer,macular degenerationand other eye diseases, certaingenetic conditionsandHIV/AIDS.

The U.S. Food and Drug Administration (FDA) has approved two gene therapies for use in the U.S.:

Is gene therapy safe?

The first gene therapy trial was run more than thirty years ago. The earliest studies showed that gene therapy could have very serious health risks, such as toxicity, inflammation, and cancer. Since then, researchers have studied the mechanisms and developed improved techniques that are less likely to cause dangerous immune reactions or cancer. Because gene therapy techniques are relatively new, some risks may be unpredictable; however, medical researchers, institutions, and regulatory agencies are working to ensure that gene therapy research, clinical trials, and approved treatments are as safe as possible.

Comprehensive federal laws, regulations, and guidelines help protect people who participate in research studies (called clinical trials). The U.S. Food and Drug Administration (FDA) regulates all gene therapy products in the United States and oversees research in this area. Researchers who wish to test an approach in a clinical trial must first obtain permission from the FDA. The FDA has the authority to reject or suspend clinical trials that are suspected of being unsafe for participants.

The National Institutes of Health (NIH) also plays an important role in ensuring the safety of gene therapy research. NIH provides guidelines for investigators and institutions (such as universities and hospitals) to follow when conducting clinical trials with gene therapy. These guidelines state that clinical trials at institutions receiving NIH funding for this type of research must be registered with the NIH Office of Biotechnology Activities. The protocol, or plan, for each clinical trial is then reviewed by the NIH Recombinant DNA Advisory Committee (RAC) to determine whether it raises medical, ethical, or safety issues that warrant further discussion at a RAC public meeting.

An Institutional Review Board (IRB) and an Institutional Biosafety Committee (IBC) must approve each gene therapy clinical trial before it can be carried out. An IRB is a committee of scientific and medical advisors and consumers that reviews all research within an institution. An IBC is a group that reviews and approves an institution's potentially hazardous research studies. Multiple levels of evaluation and oversight ensure that safety concerns are a top priority in the planning and carrying out of gene therapy research.

The clinical trial process occurs in three phases. Phase I studies determine if a treatment is safe for people and identify its side effects. Phase II studies determine if the treatment is effective, meaning whether it works. Phase III studies compare the new treatment to the current treatments available. Doctors want to know whether the new treatment works better or has fewer side effects than the standard treatment. The FDA reviews the results of the clinical trial. If it determines that the benefits of the new treatment outweigh the side effects, it approves the therapy, and doctors can use it to treat a disorder.

What are CAR T cell therapy, RNA therapy, and other genetic therapies?

Several treatments have been developed that involve genetic material but are typically not considered gene therapy. Some of these methods alter DNA for a slightly different use than gene therapy. Others do not alter genes themselves, but they change whether or how a genes instructions are carried out to make proteins.

Cell-based gene therapy

CAR T cell therapy (or chimeric antigen receptor T cell therapy) is an example of cell-based gene therapy. This type of treatment combines the technologies of gene therapy and cell therapy. Cell therapy introduces cells to the body that have a particular function to help treat a disease. In cell-based gene therapy, the cells have been genetically altered to give them the special function. CAR T cell therapy introduces a gene to a persons T cells, which are a type of immune cell. This gene provides instructions for making a protein, called the chimeric antigen receptor (CAR), that attaches to cancer cells. The modified immune cells can specifically attack cancer cells.

RNA therapy

Several techniques, called RNA therapies, use pieces of RNA, which is a type of genetic material similar to DNA, to help treat a disorder. In many of these techniques, the pieces of RNA interact with a molecule calledmessenger RNA(or mRNA for short). In cells, mRNA uses the information in genes to create a blueprint for making proteins. By interacting with mRNA, these therapies influence how much protein is produced from a gene, which can compensate for the effects of a genetic alteration. Examples of these RNA therapies include antisense oligonucleotide (ASO), small interfering RNA (siRNA), and microRNA (miRNA) therapies. An RNA therapy called RNA aptamer therapy introduces small pieces of RNA that attach directly to proteins to alter their function.

Epigenetic therapy

Another gene-related therapy, called epigenetic therapy, affectsepigenetic changesin cells. Epigenetic changes are specific modifications (often called tags) attached to DNA that control whether genes are turned on or off. Abnormal patterns of epigenetic modifications alter gene activity and, subsequently, protein production. Epigenetic therapies are used to correct epigenetic errors that underlie genetic disorders.

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Vector Insights

The AAV segment shows a significant revenue contribution of 22.9% in 2023. Several biopharma companies are offering their viral vector platform for the development of AAV-based gene therapy product. For instance, in September 2016, Lonza signed an exclusive agreement with Massachusetts Eye and Ear to support its novel Anc-AAV gene therapy platform for development and commercialization of next-generation gene therapies based on their AAV platform. Similarly, RegenxBio had made an agreement with companies AveXis & Biogen in March 2014 and May 2016, respectively, which would allow both companies to use RegenxBios AAV vector platform for development of gene therapy molecules. Furthermore, in May 2021, Biogen Inc. and Capsigen Inc. entered into a strategic research partnership to engineer novel AAV capsids that have the possibility to deliver transformative gene therapies, which can address the fundamental genetic causes of numerous neuromuscular and CNS disorders. In July 2021, the U.S. Department of Commerces National Institute of Standards and Technology (NIST), National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL), and United States Pharmacopeia (USP) announced a collaboration to evaluate analytical methods and develop standards for AAV. As part of this partnership, NIST and USP will be conducting an interlaboratory study in which several laboratories will measure these serious quality attributes, and their results will be linked and examined. This collaboration will support the development of new promising gene therapies that will significantly advance peoples lives.

Indication Insights

The spinal muscular atrophy (SMA) segment dominated the market in 2023. Although SMA is a rare disorder, it is one of the most common fatal inherited diseases of infancy. The development of Zolgensma (AVXS-101), has proven its effectiveness in treating SMA and altering the phenotype of the illness. The FDA approved Novartis' Zolgensma approval in May 2019, which is aimed at treating the underlying cause of SMA. As of now, Zolgensma is the only gene treatment in this field to have been approved. The approval of this gene therapy is evidence of the growing use of therapies to treat serious hereditary illnesses like SMA.

The Beta-Thalassemia Major/SCD segment is anticipated to register the fastest CAGR over the forecast period. Gene therapy for SCD and -thalassemia is based on transplantation of gene-modified hematopoietic stem cells. Clinical and preclinical studies have shown the efficacy and safety of this therapeutic modality. However, several other factors, such as suboptimal gene expression levels & gene transfer efficiency, limited stem-cell dose and quality, and toxicity of myeloablative regimens are still hampering its efficacy. Despite these challenges, in June 2019, bluebird Bios Zynteglo (formerly LentiGlobin) received conditional approval in Europe for the treatment of -thalassemia and is expected to receive U.S. FDA approval in August 2022. Moreover, the product has already received Orphan Drug status by the U.S. FDA for treatment of patients with sickle cell disease (SCD). Furthermore, in April 2021, Vertex Pharmaceuticals and CRISPR Therapeutics amended partnership for the development, production, and commercialization of CTX001 in sickle beta thalassemia and cell disease. These achievements in this segment are anticipated to significantly boost the adoption of the product in this segment.

Route of Administration Insights

The intravenous segment dominated the global gene therapy market in 2023. Large number of approved products along with strong pipeline for IV candidates is the major reason for the segment dominance. The segment is also expected to emerge as the most lucrative over the forecast period.

Recent Developments

Some of the prominent players in the Gene therapy market include:

Segments Covered in the Report

This report forecasts revenue growth at global, regional, and country levels and provides an analysis of the latest industry trends in each of the sub-segments from 2021 to 2033. For this study, Nova one advisor, Inc. has segmented the global gene therapy market.

Indication

Vector Type

Route of Administration

By Region

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Gene Therapy Market Size Poised to Surge USD 52.40 Billion by 2033 - BioSpace

The global cancer gene therapy market size was accounted for USD 2.95 billion in 2023 and it is increasing around USD 18.11 billion by 2033 with a CAGR of 19.9% from 2024 to 2033, according to a new report by Nova One Advisor.

Cancer Gene Therapy Market Overview

Cancer is a group of diseases that involve abnormal cell growth which can spread to respective parts of the body. Cancer can spread throughout the human body.Gene therapyis a kind of treatment in which the genes that are not normal or are missing in the patients cells are replaced with normal genes. Cancer gene therapy is a technique for treating cancers where the therapeutic DNA is introduced in the gene of the individual suffering from cancer.

Due to a high success rate in preclinical as well asclinical trials, cancer gene therapy is gaining high popularity all over the world. There are numerous techniques utilized in cancer gene therapy. In one of the gene therapy techniques, either the mutated gene is replaced with a healthy gene, or the gene is inactivated if its function is abnormal. In a newly developed technique, new genes can be introduced in the body of the patient to help fight against cancer cells.

Further, the ongoing extensive research and development (R&D) strategies implemented bybiopharmaceuticalfirms for producing novel therapeutic drugs are driving the market growth notably.

The market players can aim towards expansions, collaborations, joint ventures, acquisitions, and partnerships to advance capabilities in gene therapy. This would help in yielding effective therapeutic drugs for treating different kinds of cancers. In April 2022, GSK plc announced the acquisition of Sierra Oncology for 1.6 billion ($1.9 billion). This acquisition would help GSK plc in enhancing its capabilities with respect to targeted therapies for treating rare forms of cancer.

Biotechnologyfirms are evaluating novel gene therapy vectors for increasing levels of protein production/gene expression, reducing immunogenicity, and improving durability.

The top cancers in terms of the count of new cases in 2020 all over the world were Lung Cancer (2,206,771 cases),Breast Cancer(2,261,419 cases),Prostate Cancer(1,414,259 cases), Colorectal Cancer (1,931,590 cases), Stomach Cancer (1,089,103 cases), and Liver cancer (905,677 cases). In 2018, there were around 134,632 new cancer cases and 89,042 cancer-related fatalities. Breast and liver cancers were among the most common tumors in terms of incidence and mortality. The high prevalence of breast cancer cases enhances the scope for CRISPR/Cas9-based gene editing for breast cancer therapy and VISA-claudin4-BikDD gene therapy.

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Key Takeaways:

Cancer Gene Therapy Market Size in U.S. 2024 to 2033

The U.S. cancer gene therapy market size was valued at USD 1.25 billion in 2023 and is anticipated to reach around USD 7.94 billion by 2033, growing at a CAGR of 20.31% from 2024 to 2033.

North America accounted for the largest share of over 61.15% in 2023. This is attributed to the conducive environment facilitated by the government and the National Cancer Institute that supports research and development activities to enhance cancer therapeutics. Further, the presence of key market players in the region, their research efforts in devising gene therapy for cancer treatment, and collaborative efforts among market players to enhance research are boosting the market growth in the region. For instance, in August 2022, Merck & Co., Inc., collaborated with Orna Therapeutics Inc., for discovery, development, and commercialization of multiple programs, inclusive of utilization of mRNA for cancer gene therapy.

Europe is estimated to be the fastest-growing region over the forecast period due to increase in research funding for novel therapeutics by government bodies and increasing demand for novel therapeutics that could help combat the growing incidence of cancer cases across the region. Moreover, The European Unions Horizon Europe Mission on Cancer was launched in September 2023 so as to offer funds to a broad spectrum of activities that are intended to lower Europes cancer burden by accelerating research and innovation in cancer therapeutics. The mission is anticipated to help over 3 million cancer survivors by the year 2033.

The cancer gene therapy market in the Asia Pacific (APAC) region is segmented into India, China, Japan, South Korea, and the rest of the Asia Pacific (APAC) region. China dominated the Asia Pacific region followed by Japan and India in 2023.

The Latin America, Middle East, and African (LAMEA) cancer gene therapy market is segmented into North Africa, South Africa, Saudi Arabia, Brazil, Argentina, and the Rest of LAMEA. The Middle East and the Latin America region are anticipated to have notable growth in the cancer gene therapy market during the forecast period. Brazil held the largest share in the LAMEA region in 2023. Due to low literacy, uncertainty, and civil war in African countries, the cancer gene therapy market in Africa is expected to grow at a comparatively slow rate.

What are the importance of Cancer Gene Therapy?

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Types of gene therapy for cancer

Gene therapy aims tocontrolthe altered genesor genetic mutationsof a cancertoprevent the cancers growth.This approach to using our own cells and genes to treat cancer is called somatic gene therapy.Thistype of gene therapydoes not impact germ-line cells in the reproductive system, meaning none of the genetic changescan bepassedon to otherfamily members.

There are four types of somatic gene therapy: gene editing; gene replacement; gene addition; and gene inhibition.

Gene editing is correcting the cells gene to fix the imbalance by snipping out the faulty part of the gene and changing the cancers DNA. This type of gene therapy may correct the alteration rather than trying to remove it. Gene replacement is just that: replacing the faulty or nonworking gene with a healthy copy of it. This type of gene therapy is another form of trying to fix the genetic change rather than trying to remove it.

Gene addition is adding novel genetic code to a different cell usually an immune system fighter cell to help it combat the protein linked to the damaged gene. CAR T-cell therapy is an example of gene addition. This form of gene therapy isnt adding a copy of an already-existing gene but rather an entirely new gene usually with the intent of killing the cancer cell via the immune system. Doctors may also add a new gene directly to the cancer cell that causes the cancer cell to commit apoptosis (kill itself).

Gene inhibition simply shuts down the faulty gene. This can either kill the cell or prevent it from acting in a cancerous manner, such as growing and replicating exponentially.

Steps of gene therapy

Gene therapy is a new and potentially curative approach to treating cancer, but researchers still have so much to learn. While the steps below may seem straightforward, each part of the process requires years of study to develop the technologies.

Researchers must first identify the gene and protein linked to the cancer. The next steps are:

Steps of CAR T-cell therapy

CAR T-cell therapy has a slightly different process than more direct forms of gene therapy. CAR T cells are lab-generated fighter cells with specific, anti-cancer genetic code. Adding this genetic code is the gene therapy component of CAR T-cell therapy. CAR stands for chimeric antigen receptor, which is the new genetic code added to the T cells.

There are six CAR T-cell therapy agents approved by the U.S. Food and Drug Administration for different blood cancers. These approvals validate CAR T cells as an effective form of cancer gene therapy to improve patient life expectancy.

Doctors first draw blood from a patient and separate the T cells, which are white blood cells leading the immune systems defense against viruses, diseases and more unwanted intruders. T cells aim to protect the body from cancer, but theyre often ineffective at doing so.

The process of drawing blood from patients and separating the T cells is called apheresis.

After removing T cells from the body, the steps of CAR T-cell therapy are:

A similar process occurs for CAR NK-cell therapy. Scientists create chimeric antigen receptors to strengthen natural killer (NK) cells, another white blood cell of the immune system.

How long does CAR T-cell therapy take?

There are six CAR T-cell therapies approved for types of three blood cancers: myeloma, leukemia and lymphoma. CAR T-cell therapy infusions can take place in an inpatient or outpatient care setting, but the patient must be closely monitored at all times.

CAR T-cell therapy can lead to side effects, most notable cytokine release syndrome.

The entire CAR T-cell process lasts approximately one month, not including the recovery time after treatment:

For the first seven days after receiving the CAR T-cell infusion, patients must remain under medical supervision. For weeks 2-4 of the post-infusion timeline, patients must remain within a short drive of their medical facility to respond to any issues.

The total recovery period from CAR T-cell therapy is usually 2-3 months following infusion, according to the Dana-Farber Cancer Institute.

There are several studies for CAR T-cell therapies for cancer. Participating in a clinical trial helps advance cell and gene therapy research and can advance much-needed therapies to more patients in need.

Therapy Insights

Gene induced immunotherapy dominated the market with a revenue share of over 41.9% in 2023. The dominance of the segment can be attributed to research studies aiming to lower the proliferation of various types of cancer by strengthening the immune system. Many gene therapies for cancers are designed on the basis of immunotherapy elements. For instance, PROVENGE (by Dendreon Corporation) is an autologous cellular immunotherapy designed to stimulate a subjects immune system against prostate cancer.

Oncolytic virotherapy is expected to grow at the fastest rate over the forecast period owing to the favorable outcomes and the level of efficacy offered by oncolytic virotherapy. Oncolytic viruses can combat cancer cells without disturbing the healthy cells in vicinity by stimulating natural killer cells. Moreover, there are lucrative research grants for the research on oncolytic virotherapy. For instance, in July 2022, the researchers at the Center for Nuclear Receptors and Cell Signaling at the University of Houston received a USD 1.8 million grant from the National Institutes of Health to work on oncolytic virotherapy.

End-use Insights

Biopharmaceutical companies led the market with a revenue share of over 50.0% in 2023. This is attributed to the increasing global prevalence of different types of cancers owing to various hereditary, environmental, and lifestyle risk factors. Moreover, the market is driven by increasing adoption of elemental gene therapy options by biopharmaceutical giants to design cancer therapeutic regimes. Many novel therapeutic drugs are under different phases of trials and firms are striving to market them in different regions across the globe. For instance, in January 2020, bluebird bio, Inc. launches its drug, ZYNTEGLO in Germany to be used as a one-time gene therapy solution for patients aged 12 years and above.

The biopharmaceutical companies segment is projected to grow at the fastest rate over the forecast period. The increasing global prevalence of malignant tumors is a key factor driving the market. Moreover, an increased interest in oncology therapeutics research and development is resulting in a rise in the number of FDA approvals of gene therapy drugs. For instance, there are 6 FDA-approved cancer gene therapy drugs with Tecratus, Abcema, and Kymriah being the recent approvals.

Recent Developments:

Some of the prominent players in the Cancer gene therapy market include:

Segments Covered in the Report

This report forecasts revenue growth at global, regional, and country levels and provides an analysis of the latest industry trends in each of the sub-segments from 2023 to 2033. For this study, Nova one advisor, Inc. has segmented the global cancer gene therapy market.

Therapy

End-use

By Region

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Excerpt from:
Cancer Gene Therapy Industry is Rising Rapidly Up to USD 18.11 Bn by 2033 - BioSpace

-First efficacy signals demonstrated for a gene therapy under development for Oculopharyngeal Muscular Dystrophy (OPMD) which affects ~15,000 patients worldwide-

- BB-301 facilitated improvements across multiple measures of swallowing function in the first Phase 1b/2a clinical study subject as compared to pretreatment assessments conducted during the observational natural history portion of the study-

-Virtual R&D Day being held today at 9:00 am EDT, details below-

HAYWARD, Calif., April 18, 2024 (GLOBE NEWSWIRE) -- Benitec Biopharma Inc. (NASDAQ: BNTC) (Benitec or Company), a clinical-stage, gene therapy-focused, biotechnology company developing novel genetic medicines based on its proprietary Silence and Replace DNA-directed RNA interference (ddRNAi) platform, today announces positive interim clinical data from the 90-day timepoint following the administration of BB-301 to the studys first subject (Subject 1) treated in the BB-301 Phase 1b/2a single-arm, open-label, sequential, dose-escalation cohort study (NCT06185673) in Oculopharyngeal Muscular Dystrophy (OPMD). BB-301 has been granted Orphan Drug designation by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) Committee for Orphan Medicinal Products (COMP).

To date, no clinical studies have systematically demonstrated a clinical improvement in OPMD patients across both objective and subjective measures of swallowing. We are, therefore, pleased to report positive interim clinical data from multiple radiographic measures as well as subject-reported outcome measures from the first subject treated with BB-301, said Jerel A. Banks, M.D., Ph.D., Executive Chairman and Chief Executive Officer of Benitec. We are highly encouraged by these early clinical trial results and for the hope that they may offer to patients and caregivers, and we look forward to reporting additional results and continuing to treat patients as they enter the dosing portion of the study from the Natural History observational lead-in period.

BB-301 Interim Clinical Study Results:

During the OPMD Natural History Study, which represents the pre-dose observational period for each subject, Subject 1 experienced progressive worsening of dysphagia as demonstrated by the results of the videofluoroscopic swallowing studies (VFSS), the cold water timed drinking test, and the key subject-reported outcome measure (the Sydney Swallow Questionnaire). Videofluoroscopic swallowing studies represent the gold standard analytical method for the quantitative assessment of dysphagia (swallowing difficulty) in the clinical setting.

At the 90-day timepoint following the administration of BB-301, Subject 1 demonstrated improvements in key videofluoroscopic assessments which correlated with the observation of similar improvement in the key subject-reported outcome measure as compared to the average values for the respective assessments completed during the pre-dose observational period (as summarized in Figure 1). Notably, the results of many assessments completed at the 90-day timepoint demonstrated improvements over the initial measurements assessed at the subjects first visit for the natural history observational study which occurred more than 12 months prior to the 90-day assessment.

The most significant VFSS improvements at Day 90 were observed for swallowing tasks centered on the evaluation of pharyngeal constrictor muscle function and swallowing efficiency in the context of the consumption of thin liquids, solid foods and thick, non-solid foods (e.g., yogurt or pudding) (Figure 1). The VFSS improvements correlated with an improvement in the key subject-reported outcome measure the Sydney Swallow Questionnaire, indicating an improvement in swallowing function as reported by Subject 1 (Figure 1).

Figure 1: Improvement in All Outcomes at 90-Days Post-BB-301 Injection*

*Company data on file

Regarding the BB-301 safety profile observed to date, no Serious Adverse Events have been observed for the two subjects that have received BB-301. Transient Grade 2 Gastroesophageal Reflux Disease or GERD (i.e., acid reflux or heartburn) was observed for the two subjects that received BB-301. For both subjects, the GERD resolved following the completion of a short course of common prescription medications approved for the treatment of GERD.

OPMD is a rare progressive muscle-wasting disease caused by a mutation in the poly(A)-binding protein nuclear 1 (PABPN1) gene, for which there is currently no effective drug therapy. The disease is characterized by swallowing difficulties (dysphagia), limb weakness and eyelid drooping (ptosis). Dysphagia worsens over time and can lead to chronic choking, regurgitation, aspiration pneumonia, and in severe cases, death. Available clinical and surgical interventions are limited in scope and effectiveness and do not address the underlying progressive muscle weakness.

Virtual R&D Event Information: This live virtual R&D Event, featuring two OPMD key opinion leaders, will be held at 9:00 AM EDT today, April 18th, 2024 and can be accessed here. The event replay will be placed on the News & Events tab on the Investor page of the Benitec website.

About BB-301

BB-301 is a novel, modified AAV9 capsid expressing a unique, single bifunctional construct promoting co-expression of both codon-optimized Poly-A Binding Protein Nuclear-1 (PABPN1) and two small inhibitory RNAs (siRNAs) against mutant PABPN1. The two siRNAs are modeled into microRNA backbones to silence expression of faulty mutant PABPN1, while allowing expression of the codon-optimized PABPN1 to replace the mutant with a functional version of the protein. We believe the silence and replace mechanism of BB-301 is uniquely positioned for the treatment of OPMD by halting mutant expression while providing a functional replacement protein.

About Benitec Biopharma, Inc.

Benitec Biopharma Inc. (Benitec or the Company) is a clinical-stage biotechnology company focused on the advancement of novel genetic medicines with headquarters in Hayward, California. The proprietary Silence and Replace DNA-directed RNA interference platform combines RNA interference, or RNAi, with gene therapy to create medicines that simultaneously facilitate sustained silencing of disease-causing genes and concomitant delivery of wildtype replacement genes following a single administration of the therapeutic construct. The Company is developing Silence and Replace-based therapeutics for chronic and life-threatening human conditions including Oculopharyngeal Muscular Dystrophy (OPMD). A comprehensive overview of the Company can be found on Benitecs website at http://www.benitec.com.

Forward Looking StatementsExcept for the historical information set forth herein, the matters set forth in this press release include forward-looking statements, including statements regarding Benitecs plans to develop and potentially commercialize its product candidates, the timing of completion of pre-clinical and clinical trials, the timing of the availability of data from our clinical trials, the timing and sufficiency of patient enrollment and dosing in clinical trials, the timing of expected regulatory filings, the clinical utility and potential attributes and benefits of ddRNAi and Benitecs product candidates, the intellectual property position, and other forward-looking statements.

These forward-looking statements are based on the Companys current expectations and subject to risks and uncertainties that may cause actual results to differ materially, including unanticipated developments in and risks related to: unanticipated delays; further research and development and the results of clinical trials possibly being unsuccessful or insufficient to meet applicable regulatory standards or warrant continued development; the ability to enroll sufficient numbers of subjects in clinical trials; determinations made by the FDA and other governmental authorities; the Companys ability to protect and enforce its patents and other intellectual property rights; the Companys dependence on its relationships with its collaboration partners and other third parties; the efficacy or safety of the Companys products and the products of the Companys collaboration partners; the acceptance of the Companys products and the products of the Companys collaboration partners in the marketplace; market competition; sales, marketing, manufacturing and distribution requirements; greater than expected expenses; expenses relating to litigation or strategic activities; the Companys ability to satisfy its capital needs through increasing its revenue and obtaining additional financing, given market conditions and other factors, including our capital structure; our ability to continue as a going concern; the length of time over which the Company expects its cash and cash equivalents to be sufficient to execute on its business plan; the impact of the COVID-19 pandemic, the disease caused by the SARS-CoV-2 virus and similar events, which may adversely impact the Companys business and pre-clinical and clinical trials; the impact of local, regional, and national and international economic conditions and events; and other risks detailed from time to time in the Companys reports filed with the Securities and Exchange Commission. The Company disclaims any intent or obligation to update these forward-looking statements.

Investor Relations Contact: Irina Koffler LifeSci Advisors, LLC (917) 734-7387 ikoffler@lifesciadvisors.com

A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/a47d2f41-3feb-49a7-a58f-62e5b0dd4332

Originally posted here:
Benitec Biopharma Reports Positive Interim Clinical Trial Data for First OPMD Subject Treated with BB-301 in Phase 1b ... - GlobeNewswire

A single subretinal dose of a gene therapy was not only well tolerated among patients with neovascular age-related macular degeneration (nAMD), but there was sustained expression of the RGX-314 protein for at least 2 years, showing the potential to control exudation. The results of the phase I/IIa dose escalation trial were published in The Lancet.1

Age-related macular degeneration (AMD) causes vision loss that can turn into partial blindness.

Image credit: Syda Productions - stock.adobe.com

RGX-314, also known as ABBV-RGX-314, is an adeno-associated virus serotype 8 vector that provides potential continuous suppression of VEGF-A. nAMD, also called wet AMD, causes faster vision loss than AMD and, while it doesnt cause complete blindness, can cause patients to lose central vision.2

Real-world outcomes of long-term nAMD treatment have been inferior to those seen in clinical trials because of undertreatment or nonadherence with visits for injections. Therefore, there is strong motivation to develop treatments that provide sustained suppression of VEGF-A, the authors explained.

The open-label, multiple-cohort, multicenter, phase I/IIa, dose-escalation study was conducted at 8 sites in the US with 68 patients. On day 1, all patients received intravitreal ranibizumab. At week 2, 42 who demonstrated the required anatomic response received a subretinal injection of RGX-314. There were 5 different doses being evaluated with 12 patients placed into each cohort based on dosing. The mean (IQR) age at baseline was 80 years (74-85), nearly all (41 of 42) patients were White, and 52% were female.

While all patients experienced at least 1 treatment-emergent adverse event (TEAE), most were grade 1 or 2. The most common TEAEs were postprocedure conjunctival hemorrhage and retinal pigmentary changes. There were also 7 instances of a retinal degeneration event, which were mostly grade 1, typically occurred 6 to 12 months after the gene therapy was administered, and had not resolved at the end of the study.

In 9 of 46 study eyes, reduced visual acuity was reported, although 6 of these were mild or moderate and deemed unrelated to RGX-314. However, the other 3 events were possibly related to the therapy.

The mean baseline best-corrected visual acuity (BCVA) was maintained or improved in 4 of the 5 cohorts, while cohort 1, which received 3x109 genome copies per eye, experienced a gradual reduction in BCVA over time. Patients in cohorts 3 through 5 who did not receive any supplemental antiVEGF-A injections throughout the last year of the study maintained or improved baseline BCVA.

"The publication of the ABBV-RGX-314 Phase I/IIa trial results in The Lancet reinforces the encouraging long-term clinical data observed using subretinal delivery and underscores the potential of ABBV-RGX-314 gene therapy to offer a new approach to the clinical management of wet AMD," Jeffrey S. Heier, MD, director of the Vitreoretinal Service and director of Retina Research at Ophthalmic Consultants of Boston, and primary investigator for the trial, said in a statement.3 "Wet AMD is a chronic, life-long disease and real-world evidence shows patients are losing significant vision over time, and the burden of frequent anti-VEGF injections needed to manage their wet AMD is a major reason why. A single treatment of ABBV-RGX-314 that can potentially provide long-lasting treatment outcomes and a strong safety profile would offer a novel approach to treating this serious and blinding disease."

In an interview4 ahead of the Angiogenesis, Exudation, and Degeneration 2023 meeting, Charles C. Wykoff, MD, PhD, director of research at Retina Consultants of Texas; chair of research, Retina Consultants of America; and deputy chair of ophthalmology for the Blanton Eye Institute, Houston Methodist Hospital; and coauthor on the study, explained that a gene therapy for the most common cause of irreversible blindness would be a tremendous step forward for the opportunity for management of this chronic disease.

He also noted that while gene therapy holds the promise of being one and done, data have shown that some patients do need ongoing therapy.5

"Even if we are using gene therapy, it's important to realize that these patients will continue to need retinal care and retinal follow-up," he said. "You're looking for signs of efficacy, you're monitoring them for safety, you're making sure that they get any retreatments if they need them. Of course, there's a host of other retinal issues that may come up in these patients. They're going to continue to need retina care, certainly, even in the context of gene therapy."

Reference

1. Campochiaro PA, Avery R, Brown DM, et al. Gene therapy for neovascular age-related macular degeneration by subretinal delivery of RGX-314: a phase 1/2a dose-escalation study. Lancet. 2024:S0140-6736(24)00310-6. doi:10.1016/S0140-6736(24)00310-6

2. Age-related macular degeneration. National Eye Institute. June 22, 2021. Accessed April 12, 2024. https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/age-related-macular-degeneration

3. REGENXBIO announces Lancet publication of phase I/IIa study evaluating ABBV-RGX-314 as a one-time gene therapy for wet AMD. REGENXBIO. News release. March 28, 2024. Accessed April 12, 2024. https://regenxbio.gcs-web.com/news-releases/news-release-details/regenxbio-announces-lancet-publication-phase-iiia-study

4. Joszt L. Dr Charles Wykoff: gene therapy for wet AMD would be a tremendous opportunity. The American Journal of Managed Care. May 21, 2023. Accessed April 12, 2024. https://www.ajmc.com/view/dr-charles-wykoff-gene-therapy-for-wet-amd-would-be-a-tremendous-opportunity

5. Joszt L. Dr Charles Wykoff discusses gene therapy to treat wet age-related macular degeneration. The American Journal of Managed Care. April 23, 2023. Accessed April 12, 2024. https://www.ajmc.com/view/dr-charles-wykoff-discusses-gene-therapy-to-treat-wet-age-related-macular-degeneration

Read the original post:
Gene Therapy Well Tolerated in Wet AMD, Shows Promise in Visual Acuity - AJMC.com Managed Markets Network

You can add Nov. 16, 2023, to July 16, 1945 the day nuclear power moved from the theoretical to the actual as an entry to the list of consequential moments for everyones favorite vertebrate, Homo sapiens.

The news was easy to miss, but there it was. The United Kingdom announced that it would be the first country in the world to approve the use of gene editing as a medical therapy, starting with two inherited types of anemia: beta-thalassemia, and the more widely known sickle cell anemia. The U.S. Food and Drug Administration (FDA) followed suit three weeks later.

Its official: we humans are going to mess with our DNA, our original blueprints. DNA is the genetic instructions dictating how we look and behave, and that define what diseases we may develop, be prone to or be free of. With our ever-improving gene-editing skills, we are now prepared to peel back the pages of this ancient and sacred text and write the story the way we want to hear it.

DNA makes up the letters of lifes instruction manual for humans or any living thing. Genes organize those letters into words and paragraphs. Chromosomes organize those genes into chapters. In humans, each cell has 23 pairs of chromosomes. Inside the cell, DNA provides the formula for manufacturing specific proteins. Its the blueprint that tells each cell what to build, and how to build it.

Unfortunately, DNA can get altered or damaged, an occurrence thats referred to as a mutation. A mutation can be either inherited or newly acquired. It can cause the gene to produce a faulty product or no product at all. In the case of sickle cell disease, a mutation in the gene that codes for hemoglobin a complex protein that allows red blood cells to shuttle oxygen from the lungs to the body can lead to a whole lot of pain and suffering.

Red blood cells are flexible, allowing them to scooch through tiny capillaries where they unload their oxygen. In sickle cell disease, the mutation in the hemoglobin molecule can cause a red blood cell to change shape from a circle to a sickle. Sickled red blood cells lack flexibility, so they plug up the very capillaries they were supposed to be sliding through. Just as a traffic accident can lead to a pileup of cars behind it, one stuck sickled cell can trigger an upstream backup of stuck sickled cells.

Traffic jams are a pain, but a sickle cell attack aptly termed a crisis produces a deep, aching pain that may be unrivaled in human suffering. As capillaries and small arteries plug up, downstream tissues are left without oxygen. These blood-starved tissues begin screaming for oxygen as if their lives depended on it which they do.

Although a sickle cell crisis can cause excruciating pain, thankfully it is only rarely lethal. With pain medications, intravenous fluids, blood transfusions and oxygen support, the pain eventually eases. But repeated episodes take their toll on the body, significantly shortening the life expectancy of those with the disease.

Those with sickle cell disease (SCD) carry two copies of a sickling-prone hemoglobin gene (HbS). One copy comes from each parent. Those with sickle cell trait (SCT) have just one copy of HbS, but thats not enough to cause sickling except in rare circumstances like scuba diving or mountain climbing.

The sickle cell gene seems to have originated in sub-Saharan Africa, where having a single copy of the gene having SCT protects against severe malaria infections. Thats because the parasite that causes malaria, which reproduces by infecting red blood cells, has a harder time doing that inside cells carrying a lone sickle gene.

Although the prevalence of the sickle cell gene remains highest in sub-Saharan Africa, slavery and migration patterns have expanded its global range, so that today SCD can affect people of Hispanic, Southern European, Middle Eastern or Asian Indian backgrounds.

In the United States, 7% to 8% of Black newborns carry the sickle cell trait. In addition, 0.7% of Hispanic newborns, 0.3% of white newborns, and 0.2% of Asian or Pacific Islander newborns carry the trait. One out of every 365 Black newborns will have SCD. In total, about 100,000 people in the U.S. and 20 million people worldwide have SCD. Thats a lot of people hoping for a cure.

Casgevy is the first FDA-approved therapy to use CRISPR gene-editing technology. CRISPR is an acronym we can all be grateful for because it eliminates a phrase we will never be able to remember: clustered regularly interspaced short palindromic repeats.

In the case of Casgevy, CRISPR is used to create a line of red blood cells that manufacture hemoglobin F (HbF) thats F as in fetus. HbF has stronger oxygen-binding characteristics than adult hemoglobin (HbA). Thats because in the womb humans are breathing through the mothers placenta, and not through the lungs, which are filled with amniotic fluid. HbF production typically gets turned off soon after birth. Thats unfortunate for those with sickle cell disease who carry HbS, not HbA because HbF helps prevent sickling.

Casgevy turns HbF production back on.

Lyfgenia works by giving people with sickle cell disease a line of blood cells that can manufacture a form of adult hemoglobin (HbA).

Neither Casgevy nor Lyfgenia completely eliminates sickle cells, but they dilute the concentration of sickle-prone cells, thereby preventing sickle cell crises.

No surprise treatment with Casgevy and Lyfgenia is more complicated than what I just described. It requires removing stem cells from the blood. Stem cells are a little like the queen bee in a hive: They produce all the cells that will keep the body vigorous and healthy. In this application, the stem cells of interest are the ones that manufacture the new red blood cells needed to replace those at the end of their 120-day life span (or 20 to 30 days for fragile sickle cells). After these blood stem cells are removed and sent to the lab for gene therapy, the patient is given chemotherapy to decrease the number of stem cells making sickled red blood cells. This makes room for the new-and-improved stem cells.

Chemotherapy comes in a variety of potencies, and in this case, its fairly potent the kind you need to be in the hospital for. Following the gene therapy infusion, itll be 3 to 6 more weeks in the hospital waiting for the body to recover from the chemotherapy and for the modified stem cells to start growing back in serious numbers.

Like nuclear power or artificial intelligence, the technology of gene therapy brings great promise but also serious risks and ethical concerns.

There are the risks of the treatment itself: Did the gene therapy get inserted into the right gene location, and is it functioning correctly? Or did it end up in the wrong spot, altering the function of genes that we meant to leave alone?

There is the ethical question of who will get stem cell therapy. The medical complexity and steep cost of stem cell therapy a cool $2.2 million for a Casgevy treatment, and $3.1 million for Lyfgenia make it a boutique item only the haves will be able to afford.

And there are the ethics of how and where we will apply the technology. Although history teaches us that H. sapiens is an inventive and curious creature, we also are a never-quite-satisfied, boundary-pushing and occasionally nefarious lot. While were using gene therapy to eliminate sickle cell disease or perhaps someday Alzheimers, cardiovascular disease or what have you someone is going to ask: Whats the harm in getting rid of things like nearsightedness, balding, belly fat, wrinkles? And while were at it, why not use gene therapy to make sure we or our offspring have what it takes to compete in the NBA or the Ivy League, Hollywood or the Navy Seals? And can we eliminate dying?

Dont think we humans will go there? Comedian and futurist Jon Stewart told Stephen Colbert he sees it going this way: The world ends. The last words man utters are somewhere in a lab. A guy goes, Huh-huh. It worked!

Scientists disagree on whether Stewart was joking but recommend further research.

Relevant reading

When Winter Came

Dr. Pierre Sartor wrote an inspiring first-person account of how he treated more than 1,000 patients and by his reckoning, lost only five which lay forgotten in a lockbox of family artifacts until it was discovered decades later by his granddaughter, Beth Obermeyer, a journalist and author of

Read the original here:
Messing with the blueprints: Gene therapy has arrived - Mayo Clinic Press

Wang, D. & Gao, G. State-of-the-art human gene therapy: part II. Gene therapy strategies and clinical applications. Discov. Med. 18, 151161 (2014).

PubMed PubMed Central Google Scholar

Adams, D. et al. Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis. N. Engl. J. Med. 379, 1121 (2018).

Article CAS PubMed Google Scholar

Wang, J. et al. AAV-delivered suppressor tRNA overcomes a nonsense mutation in mice. Nature 604, 343348 (2022).

Article CAS PubMed PubMed Central Google Scholar

Wang, D. & Gao, G. State-of-the-art human gene therapy: part I. Gene delivery technologies. Discov. Med. 18, 6777 (2014).

PubMed PubMed Central Google Scholar

Bulcha, J. T., Wang, Y., Ma, H., Tai, P. W. L. & Gao, G. Viral vector platforms within the gene therapy landscape. Sig. Transduct. Target. Ther. 6, 53 (2021).

Article CAS Google Scholar

Atchison, R. W., Casto, B. C. & Hammon, W. M. Adenovirus-associated defective virus particles. Science 149, 754756 (1965).

Article CAS PubMed Google Scholar

Hoggan, M. D., Blacklow, N. R. & Rowe, W. P. Studies of small DNA viruses found in various adenovirus preparations: physical, biological, and immunological characteristics. Proc. Natl Acad. Sci. 55, 14671474 (1966).

Article CAS PubMed PubMed Central Google Scholar

Samulski, R. J., Berns, K. I., Tan, M. & Muzyczka, N. Cloning of adeno-associated virus into pBR322: rescue of intact virus from the recombinant plasmid in human cells. Proc. Natl Acad. Sci. 79, 20772081 (1982).

Article CAS PubMed PubMed Central Google Scholar

Laughlin, C. A., Tratschin, J. D., Coon, H. & Carter, B. J. Cloning of infectious adeno-associated virus genomes in bacterial plasmids. Gene 23, 6573 (1983).

Article CAS PubMed Google Scholar

Srivastava, A., Lusby, E. W. & Berns, K. I. Nucleotide sequence and organization of the adeno-associated virus 2 genome. J. Virol. 45, 555564 (1983).

Article CAS PubMed PubMed Central Google Scholar

Samulski, R. J., Chang, L. S. & Shenk, T. A recombinant plasmid from which an infectious adeno-associated virus genome can be excised in vitro and its use to study viral replication. J. Virol. 61, 30963101 (1987).

Article CAS PubMed PubMed Central Google Scholar

Gao, G. P. et al. Novel adeno-associated viruses from rhesus monkeys as vectors for human gene therapy. Proc. Natl Acad. Sci. 99, 1185411859 (2002).

Article CAS PubMed PubMed Central Google Scholar

Gao, G. et al. Clades of Adeno-associated viruses are widely disseminated in human tissues. J. Virol. 78, 63816388 (2004).

Article CAS PubMed PubMed Central Google Scholar

Cheung, A. K., Hoggan, M. D., Hauswirth, W. W. & Berns, K. I. Integration of the adeno-associated virus genome into cellular DNA in latently infected human Detroit 6 cells. J. Virol. 33, 739748 (1980).

Article CAS PubMed PubMed Central Google Scholar

Laughlin, C. A., Cardellichio, C. B. & Coon, H. C. Latent infection of KB cells with adeno-associated virus type 2. J. Virol. 60, 515524 (1986).

Article CAS PubMed PubMed Central Google Scholar

Wang, D., Tai, P. W. L. & Gao, G. Adeno-associated virus vector as a platform for gene therapy delivery. Nat. Rev. Drug Discov. 18, 358378 (2019).

Article CAS PubMed PubMed Central Google Scholar

Dunbar, C. E. et al. Gene therapy comes of age. Science 359, eaan4672 (2018).

Article PubMed Google Scholar

Keeler, A. M. & Flotte, T. R. Recombinant adeno-associated virus gene therapy in light of luxturna (and Zolgensma and Glybera): where are we, and how did we get here? Annu. Rev. Virol. 6, 601621 (2019).

Article CAS PubMed PubMed Central Google Scholar

Wang, D., Zhang, F. & Gao, G. CRISPR-based therapeutic genome editing: strategies and in vivo delivery by AAV vectors. Cell 181, 136150 (2020).

Article CAS PubMed PubMed Central Google Scholar

Li, C. & Samulski, R. J. Engineering adeno-associated virus vectors for gene therapy. Nat. Rev. Genet. 21, 255272 (2020).

Article CAS PubMed Google Scholar

Tseng, Y. S. & Agbandje-McKenna, M. Mapping the AAV capsid host antibody response toward the development of second generation gene delivery vectors. Front. Immunol. 5, 9 (2014).

Article PubMed PubMed Central Google Scholar

Sonntag, F., Schmidt, K. & Kleinschmidt, J. A. A viral assembly factor promotes AAV2 capsid formation in the nucleolus. Proc. Natl Acad. Sci. 107, 1022010225 (2010).

Article CAS PubMed PubMed Central Google Scholar

Kelsic, E. D., Ogden, P. J., Sinai, S. & Church, G. M. Comprehensive AAV capsid fitness landscape reveals a viral gene and enables machine-guided design. Science 366, 11391143 (2019).

Article PubMed PubMed Central Google Scholar

Lusby, E., Fife, K. H. & Berns, K. I. Nucleotide sequence of the inverted terminal repetition in adeno-associated virus DNA. J. Virol. 34, 402409 (1980).

Article CAS PubMed PubMed Central Google Scholar

Gao, G. et al. Adeno-associated viruses undergo substantial evolution in primates during natural infections. Proc. Natl Acad. Sci. 100, 60816086 (2003).

Article CAS PubMed PubMed Central Google Scholar

Calcedo, R., Vandenberghe, L. H., Gao, G., Lin, J. & Wilson, J. M. Worldwide epidemiology of neutralizing antibodies to adeno-associated viruses. J. Infect. Dis. 199, 381390 (2009).

Article PubMed Google Scholar

Bashirians, G. et al. Global seroprevalence of neutralizing antibodies against adeno-associated virus (AAV) serotypes of relevance to gene therapy. Blood 140, 1066810670 (2022).

Article Google Scholar

Matsushita, T. et al. Adeno-associated virus vectors can be efficiently produced without helper virus. Gene Ther. 5, 938945 (1998).

Article CAS PubMed Google Scholar

Xiao, X., Li, J. & Samulski, R. J. Production of high-titer recombinant adeno-associated virus vectors in the absence of helper adenovirus. J. Virol. 72, 22242232 (1998).

Article CAS PubMed PubMed Central Google Scholar

McCarty, D. M. Jr., Young, S. M. & Samulski, R. J. Integration of adeno-associated viruS (AAV) and recombinant AAV vectors. Annu. Rev. Genet. 38, 819845 (2004).

Article CAS PubMed Google Scholar

Servellita, V. et al. Adeno-associated virus type 2 in US children with acute severe hepatitis. Nature 617, 17 (2023).

Article Google Scholar

Morfopoulou, S. et al. Genomic investigations of unexplained acute hepatitis in children. Nature 617, 564573 (2023).

Article CAS PubMed PubMed Central Google Scholar

Ho, A. et al. Adeno-associated virus 2 infection in children with non-AE hepatitis. Nature 617, 555563 (2023).

Article CAS PubMed Google Scholar

Tacke, F. Severe hepatitis outbreak in children linked to AAV2 virus. Nature 617, 471472 (2023).

Article CAS PubMed Google Scholar

Lisowski, L., Tay, S. S. & Alexander, I. E. Adeno-associated virus serotypes for gene therapeutics. Curr. Opin. Pharmacol. 24, 5967 (2015).

Article CAS PubMed Google Scholar

Issa, S. S., Shaimardanova, A. A., Solovyeva, V. V. & Rizvanov, A. A. Various AAV Serotypes and their applications in gene therapy: an overview. Cells 12, 785 (2023).

Article CAS PubMed PubMed Central Google Scholar

Verdera, H. C., Kuranda, K. & Mingozzi, F. AAV vector immunogenicity in humans: a long journey to successful gene transfer. Mol. Ther. 28, 723746 (2020).

Article CAS PubMed PubMed Central Google Scholar

Pillay, S. et al. Adeno-associated Virus (AAV) serotypes have distinctive interactions with domains of the cellular AAV receptor. J. Virol. 91, e0039117 (2017).

Article CAS PubMed PubMed Central Google Scholar

Dudek, A. M. et al. GPR108 is a highly conserved AAV entry factor. Mol. Ther. 28, 367381 (2020).

Article CAS PubMed Google Scholar

Dhungel, B. P., Bailey, C. G. & Rasko, J. E. J. Journey to the center of the cell: tracing the path of AAV transduction. Trends Mol. Med. 27, 172184 (2021).

Article CAS PubMed Google Scholar

Woodard, K. T., Liang, K. J., Bennett, W. C. & Samulski, R. J. Heparan sulfate binding promotes accumulation of intravitreally delivered adeno-associated viral vectors at the retina for enhanced transduction but weakly influences tropism. J. Virol. 90, 98789888 (2016).

Article CAS PubMed PubMed Central Google Scholar

Shen, S., Bryant, K. D., Brown, S. M., Randell, S. H. & Asokan, A. Terminal N-linked galactose is the primary receptor for adeno-associated virus 9. J. Biol. Chem. 286, 1353213540 (2011).

Article CAS PubMed PubMed Central Google Scholar

Pillay, S. et al. An essential receptor for adeno-associated virus infection. Nature 530, 108112 (2016).

Article CAS PubMed PubMed Central Google Scholar

Dudek, A. M. et al. An alternate route for adeno-associated virus (AAV) entry independent of AAV receptor. J. Virol. 92, e02213e02217 (2018).

Article PubMed PubMed Central Google Scholar

Berry, G. E. & Asokan, A. Cellular transduction mechanisms of adeno-associated viral vectors. Curr. Opin. Virol. 21, 5460 (2016).

Article CAS PubMed PubMed Central Google Scholar

Schultz, B. R. & Chamberlain, J. S. Recombinant adeno-associated virus transduction and integration. Mol. Ther. 16, 11891199 (2008).

Article CAS PubMed Google Scholar

Sonntag, F., Bleker, S., Leuchs, B., Fischer, R. & Kleinschmidt, J. A. Adeno-associated virus type 2 capsids with externalized VP1/VP2 trafficking domains are generated prior to passage through the cytoplasm and are maintained until uncoating occurs in the nucleus. J. Virol. 80, 1104011054 (2006).

Article CAS PubMed PubMed Central Google Scholar

Xiao, P. J. & Samulski, R. J. Cytoplasmic trafficking, endosomal escape, and perinuclear accumulation of adeno-associated virus type 2 particles are facilitated by microtubule network. J. Virol. 86, 1046210473 (2012).

Article CAS PubMed PubMed Central Google Scholar

Nicolson, S. C. & Samulski, R. J. Recombinant adeno-associated virus utilizes host cell nuclear import machinery to enter the nucleus. J. Virol. 88, 41324144 (2014).

Article PubMed PubMed Central Google Scholar

Kelich, J. M. et al. Super-resolution imaging of nuclear import of adeno-associated virus in live cells. Mol. Ther. Methods Clin. Dev. 2, 15047 (2015).

Article PubMed PubMed Central Google Scholar

Excerpt from:
Adeno-associated virus as a delivery vector for gene therapy of human diseases | Signal Transduction and Targeted ... - Nature.com

According to the latest research by nova one advisor, the global cell and gene therapy market size was valued at USD 18.13 billion in 2023 and is anticipated to reach around USD 97.33 billion by 2033, growing at a CAGR of 18.3% from 2024 to 2033.

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The cell and gene therapy market provides therapeutic solutions related to genes and cells. The market deals with research & development, testing, production, and distribution of products and treatment procedures related to genes and cells. Hospitals, research laboratories, pharmaceutical companies, pharmacies, research institutions, and universities are involved in delivering the applications associated with gene and cell therapies. Gene and cell therapies are developed to prevent, treat, or potentially cure numerous diseases. The potential of these therapies to cure, treat, or prevent diseases that are life-threatening increases the demand and boosts the growth of the market. Gene and cell therapies are used in blood stem cell transplantation, gene editing, engineering of the immune system, tissue regeneration, in-vivo gene transfer, cancer treatment, and treatment of different disorders. These therapies can provide better results and enhance quality of life.

North America dominated the cell and gene therapy market in 2023. North America is a developed region that has developed healthcare and research infrastructure, better facilities, and government support that boosts the growth of the market. Governments in the North American region have a huge national budget for healthcare and research. Countries like the U.S. and Canada contribute to the growth of the market in the North American region. As of now, the FDA has approved 37 products for gene and cell therapy. The U.S. has the American Society of Gene & Cell Therapy (ASGCT) for professionals, scientists, physicians, and patient advocates that help advance knowledge, education, and awareness for discovering and developing clinical applications of gene and cell therapy.

The Canadian government is also focusing on improving health with the help of genes and therapies and is launching various programs to help with this. The government launched Disruptive Technology Solutions, which will help tackle the challenges associated with gene and cell therapies. The treatment procedures will be done to cure rare genetic disorders and chronic diseases.

Key Takeaways:

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The cell and gene therapy market is exploding globally

Ground-breaking developments in next-generation cell and gene therapies (CGTs) offer curative value for patients with few to no other therapeutic interventions for either maintenance or cure within specific disease areas, many of which include rare and ultra-rare diseases.The largest therapeutic area is cancer, followed by musculoskeletal diseases and eye diseases.Multiple approved products have been launched in global markets and the number of clinical trials continues to grow. In Europe, these therapies are classified under Advanced Therapeutic Medicinal Products (ATMPs) and are driven by a diverse set of scientific advancements including CAR-T, TCR-T, stem cells, siRNA, oligonucleotides, gene editing (CRISPR, Zinc Fingers, TALENs) and viral transfection.

The global CGT market is projected to grow at a compound annual growth rate of over 36 percent from 2019-2025, to ~ 10 billion. With more than 900 companies globally focusing on CGTS and over 1,000 clinical trials being conducted, the industry could see numerous approvalsas many as 10 to 20 new advanced therapies per year starting in 2025. Moreover, 33% of these clinical trials is being conducted in Europe.1

Global biopharma companies as well as smaller, venture backed-up start-ups are rapidly investing in this complex space. In 2018, about $13 billion has been invested globally in advanced therapies such as cell, gene and gene modifying therapies. In 2019, 19 CGT-related M&A deals worth over $156 billion were completed.

As with any innovative and disruptive technology, CGT developers face challenges along several key stages of the product life cycle. Compared to chemical-based pharmaceuticals, key success factors such as enabling patient access, managing supply chain and manufacturing operations, evidencing compliance with increasingly complex regulatory requirements and alternate business models impose a greater burden.

Segments Insights:

By Therapy Insights

The market for cell and gene treatments consists of companies (organizations, sole proprietors, and partnerships) that sell the therapies they have developed. Cell therapy is the transfer of whole, living cells derived from allogeneic or autologous sources, while gene therapy is the introduction, deletion, or alteration of the genome to treat disease. The market is made up of the money that businesses creating goods for cell and gene therapy make from the sales of those items.

Cell treatment and gene therapy are the two primary product categories in this field. Gene therapy is a field of medicine that focuses on altering cells' genetic make-up to treat disease or reverse it by repairing or replacing genetic material that has been damaged. Oncology, dermatological, musculoskeletal, and other applications are among the many that are used in hospitals, ambulatory surgery centers, cancer treatment facilities, wound care facilities, and other industries.

Cell & Gene Therapy Market Revenue, By Therapy Type, 2022-2032 (USD Million)

By Therapy Type

2022

2023

2027

2031

2032

Cell Therapy

13,396.01

15,621.48

29,433.95

57,138.21

67,757.69

Gene Therapy

2,067.97

2,502.14

5,406.11

11,864.27

14,480.51

By Therapeutic class

Based on application, the market is divided into cardiovascular disease, cancer, genetic disorder, rare diseases, oncology, hematology, ophthalmology, infectious disease, neurological disorders. Among these, the infectious disease segment dominates the market in 2023. The oncological disorder segment held a revenue share of 13.53% in 2023. Research and treatment in the biomedical domains of cell therapy and gene therapy. Both treatments have the ability to lessen the underlying cause of hereditary disorders and acquired diseases. Both therapies aim to treat, prevent, or perhaps cure diseases. By repairing or changing specific cell types, or by employing cells to transport a medication across the body, cell therapy tries to treat diseases. Cell therapy involves growing or modifying cells outside of the body before injecting them into the patient. The cells may come from a donor (allogeneic cells) or the patient (autologous cells)6. By replacing, deactivating, or introducing genes into cells, either inside the body (in vivo) or outside the body, gene therapy seeks to treat disorders (ex vivo).

The market for genetic disorders is expanding as a result of factors like the high prevalence of genetic and chronic disease cases and the growing government initiatives to raise public knowledge of genetic testing and diagnosis. Researchers are developing novel techniques for screening, diagnosing, and treating patients for a variety of cardiac diseases as they investigate the genetic roots of heart and vascular illness. Some researchers are looking for new ways to nine patients who are at risk for sudden cardiac death. Others are examining how medicines that could postpone or obviate the need for cardiac surgery could benefit patients with uncommon illnesses.

The intricacy of mitochondrial genetics and the diverse clinical and biochemical symptoms of primary mitochondrial disorders (PMDs) have shown to be a significant obstacle to the development of effective disease-modifying medications. A successful clinical transition of genetic medicines for PMDs is possible, according to encouraging evidence from gene therapy trials in patients with Leber hereditary optic neuropathy and improvements in DNA editing tools.

Cell & Gene Therapy Market Revenue, By Therapeutic Class, 2022-2032 (USD Million)

By Therapeutic Class

2022

2023

2027

2031

2032

Cardiovascular Disease

744.36

882.84

1,780.08

3,697.84

4,460.03

Genetic Disorder

1,643.41

1,922.21

3,665.70

7,202.20

8,566.52

Oncology

1,936.87

2,272.26

4,385.58

8,720.66

10,403.81

Hematology

1,196.56

1,396.75

2,642.34

5,150.06

6,113.36

Ophthalmology

835.60

972.46

1,817.62

3,500.15

4,142.33

Infectious Disease

4,420.18

5,206.30

10,210.05

20,628.98

24,708.86

Neurological Disorders

658.61

777.29

1,536.51

3,129.23

3,755.58

Others

4,028.39

4,693.50

8,802.17

16,973.35

20,087.70

By Delivery Method

The market is split into In Vivo therapy and Ex Vivo therapy according to the type of therapy. In vivo therapy market is anticipated to grow exponentially throughout the projected period. When it comes to gene therapy, there are two different methods: ex vivo and in vivo, setting aside cell therapies. The altered human gene must first enter the diseased person's cells for gene therapy to take effect. There are two methods for doing this; Genetic material is supplied in vivo to afflicted cells (cancer cells or other cells) that are still present within an individual's body. After cells are collected and exposed to the genome in Ex vivo, altered genes are transferred to a person's body.

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Cell and Gene Therapy Market Size to Reach USD 97.33 Bn by 2033 - BioSpace

Advances in the treatment of ophthalmic conditions with gene therapies have led to a growing market with huge potential for the future, according to research from DelveInsight.

The industry analyst has prepared a reportindicating that the market size for gene therapies in ophthalmology reached roughly $132 million across mature markets last year.

Taking into account new therapies expected to come online in future years, this market could grow at

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Research shows stellar growth for gene therapies in ophthalmology - The Pharma Letter

A company started by University of Pennsylvania scientist Jim Wilson has received FDA approval to test a form of gene editing in infants for the first time in the United States, the company said Thursday.

The Plymouth Meeting company, iECURE, is developing a treatment for babies whose livers are unable to make a crucial enzyme.

Infants born with a severe form of the illness can lapse into a coma within a day or two of birth, their brains damaged by a buildup of ammonia. Some die soon thereafter; the rest have little recourse beyond a liver transplant.

This is the same disease that Wilson was studying in a high-profile test that resulted in a patient death in 1999. The patient in that case, Jesse Gelsinger, had a mild form of the disease. The 18-year-old died after his body rejected the virus used to deliver the treatment.

In Wilsons new approach with iECURE, the gene is delivered with a different type of virus that does not trigger the immune system a delivery method that he already has licensed for use in several other drugs.

The treatment had previously been approved for testing in the United Kingdom and Australia, iECURE said. The company is enrolling boys up to 9 months old.

This milestone is the culmination of over 8 years of pre-clinical research in my laboratory addressing gene editing strategies for severe rare liver metabolic diseases, Wilson said in a news release.

Founded in 2022, iECURE raised $65 million from venture capitalists in late 2022. That was during a period of waning investor enthusiasm for cell and gene therapy companies.

Both Penn and Wilson have an unspecified financial interest in iECURE.

See original here:
Penn scientist Jim Wilson's iECURE can start testing gene therapy in infants - The Philadelphia Inquirer