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Cell and gene therapies – Lexology

In recent years, we have seen a trend towards the launch of new gene and cell therapies with record-breaking price tags. Such headline-grabbing launches are becoming more and more frequent, as the pipeline for advanced therapies at all stages of development continues to grow at a rapid pace[1]. We are also seeing industry and payers adopting new innovative pricing models for those products, such as outcome-based reimbursement and annuity payment models. In this article, we discuss these emerging alternative pricing models and consider the impact they may have on related licensing arrangements.

Current trends

In May 2019 AveXis, a subsidiary of pharmaceutical giant Novartis, announced that it had received approval from the US Food and Drug Administration to market its gene therapy Zolgensma for the treatment of paediatric patients with spinal muscular atrophy (SMA). Although this is the first promise of a cure for this debilitating and lethal condition, the media coverage focussed instead on Zolgensmas price tag, which at $2.1 million per patient makes it (currently) the worlds most expensive single-dose medicine.

Zolgensma is illustrative of a general trend in gene and cell therapies that have reached the market in recent years and established a new standard of pricing for single-treatment medicines. While manufacturers point to the relative cost-effectiveness of such treatments (which may offer a one-off cure for severe conditions that otherwise would require several years worth of conventional treatments and care) public and private payers are concerned about this new escalating pricing paradigm.

Health care systems may be able to absorb such high prices for rare diseases with small patient populations. However, the current reimbursement systems will be under severe pressure if (as is hoped) pipelines for advanced cell and gene therapies result in treatments for common conditions such as diabetes or heart disease. The Institute for Clinical and Economic Review in the US has estimated that if gene therapies are developed to treat only one in ten American patients with a genetic condition approximately 1% of the total population the cumulative budget impact could rise to $3 trillion[2]. For comparison, the projected total healthcare spend in the US for 2019 is $3.8 trillion[3].

Alternative Pricing Models

The pharmaceutical industry has sought to counter criticism over the high price tags for gene and cell therapies by coupling these revolutionary therapies with new and unconventional pricing and reimbursement mechanisms.

One alternative structure that has been adopted is an annuity based model which spreads the payment for an expensive treatment over several years in a pre-agreed payment plan, thus minimising the up-front cost to payers.

Another approach adopted by the industry, and perhaps an even clearer way to demonstrate value to payers, has been to tie reimbursement to patient outcomes. The industry has negotiated several of these outcomes-based reimbursement models with public and private payers for cell and gene therapies. Reimbursement payments to the drug maker under this model are conditional upon the patient reaching specific clinical outcomes by set deadlines. Depending on the model, a patients failure to meet the specified clinical outcome can result in the drug maker having to refund payments received and/or forfeit any subsequent payments.

These new models are also being blended to create payment plans which combine annuity-style payments with rebates and outcomes-dependent instalments. We expect that in the years to come other creative payment models will emerge and be adapted from other therapy areas. For example, in Australia, the government has used a subscription style model that allowed it to pay a lump sum to drug makers for unlimited access for patients to curative hepatitis C treatments such as Sovaldi for a period of time.

Example annuity and outcomes-based reimbursement models for cell and gene therapies:

Licensing challenges

Cell and gene therapies often have their roots in academic research laboratories and the main players in this field of treatments have close ties and valuable licensing agreements with academic research institutions. For example, AveXis, the biotech company that developed Zolgensma, started as a spin-out to continue research conducted at the Center for Gene Therapy at Nationwide Childrens Hospital in Columbus, Ohio. To further its spinal muscular atrophy work, the biotech also licensed a patent owned by Martine Barkats, a researcher at the Institut de Myologie, Paris. Shortly after, AveXis was bought by Novartis for $8.7 billion. Cell and gene therapies such as Zolgensma will generally have more constituent parts (such as promoters, viral vectors and cell lines) than other more conventional small molecule therapies. This means that a party commercialising a cell or gene therapy will often need to license in more third party intellectual property or materials than a manufacturer of a conventional small molecule therapy. Most cell and gene therapies reaching the market are therefore likely to be underpinned by one or more licence agreements.Licensing challenges

While much has been said about the impact of alternative pricing and reimbursement mechanisms on drug makers, payers and patients, we want to also consider the impact on licensors of the intellectual property which enables the development and manufacture of a therapy. In particular, how future pricing and reimbursement models can impact the royalties payable by licensees to their licensors. One inherent challenge is that these licences are generally negotiated many years before the commencement of discussions with payers on pricing and reimbursement mechanisms, making it very difficult to predict which scenarios will be relevant down the line. The positions of all of the stakeholders in the pricing debate are also constantly evolving, especially as data on the cost-effectiveness of annuity and outcomes-based models continues to accumulate. One factor which makes things particularly difficult for licensors in forecasting potential future royalty streams for these products is that a licensor would rarely have any involvement in negotiations regarding pricing and reimbursement so will have no control over the model adopted.

Annuity model challenges

Generally a licensor will only receive royalties once the licensee has itself received (or at least invoiced) payment from payers. An annuity payment model is therefore likely to mean that royalties will also be paid in instalments potentially spread over a number of years following treatment of a patient. While in practice this may not be a large change for licensors to adjust to (as annual payments for these high price treatments are not out of line with other orphan drug costs, most of which need to be taken over a long period of time) there are also other factors to consider.

One concern that has been raised with annuity payment models is that there may be an increased risk of non-payment as over time licensees may face difficulties in collecting payments, for example because a payer stops complying with payment schedules or becomes insolvent. This may have the knock-on effect of reducing royalties due to a licensor. Licensors may seek to reduce this non-payment risk by asking that royalties are payable on sums invoiced by a licensee, rather than sums received (although this is likely to be resisted by a licensee or perhaps only accepted with caveats). Annuity-based models are also typically more complicated and more expensive for a licensee to manage administratively and those costs are likely to be deductible from sales totals before a licensors royalties are calculated.

From a legal drafting perspective, care would also need to be taken by the licensor when defining payment terms and the royalty term (which is commonly linked to patent expiry) to ensure that the licensor continued to receive royalties in respect of patients who are treated within the royalty term, notwithstanding the fact that payment may not be received until after the patents and royalty term has expired.

Outcome-based model challenges

In relation to outcome-based models, a fundamental concern for both licensors and licensees is the uncertainty associated with a model which involves an upfront payment of the full treatment price but a refund payable some months or years down the line if the clinical outcomes are not met.

If royalties are payable on net sales of the therapy on a regular basis (e.g. quarterly or annually) then unless the licence includes a mechanism to take account of outcomes-based refunds made by the licensee to payers, the licensee could find itself out of pocket, unable to recover royalties paid to the licensor despite having had to refund the therapy price to the payer. To counter this risk, a licensee may seek to build in a royalty claw back mechanism into the licence, or to delay the point at which royalties are payable until after the relevant patient has met the required outcome. However, a licensor is unlikely to accept a significant delay in payment of royalties, particularly where the licensee has itself been paid. Academic licensors, with an obligation to invest income from technology transfer activities into research and the provision of education, are particularly unlikely to agree a royalty claw back structure which could force them to refund royalties or milestones a year or more after having received them.

One alternative option may be to agree that the licensee can make deductions against future royalty payments. A further alternative could be for some portion of the royalties paid to be retained in escrow for a period of time, to be released to the licensor upon achievement of a positive clinical outcome or expiry of a set period of time. However, escrow arrangements necessarily increase the complexity of agreements and are difficult to negotiate upfront when payment and reimbursement models and the associated outcome triggers have not yet been set.

A compromise?

As we have outlined in this article, although there are some things each party can consider at the outset of negotiating a licence, getting into protracted negotiations about hypothetical scenarios is unlikely to be attractive to either party.

The parties may wish to adopt an alternative approach of including robust governance provisions in the licence to deal specifically with this issue. For example, establishing a committee comprised of representatives of both parties to oversee and review issues relating to pricing and reimbursement. This may give the licensor a clearer oversight (and potentially input) into decisions which may impact future royalty streams and may present the licensee with an opportunity to propose alternative payment structures to support its desired pricing model. This could be combined with a mechanism for proposing and agreeing amendments to payment provisions in the licence if necessary to accommodate pricing and reimbursement issues which were unforeseen at the outset. Of course the success of such mechanisms will depend on the strength of the relationship between the parties and a combined willingness to work together and potentially compromise. It would also be important to ensure it is clear what happens where the parties cannot agree (e.g. escalation? expert determination? preservation of the status quo?). However, in a future where pricing and reimbursement issues are only likely to become more complex and of key importance to the success of complex treatments such as cell and gene therapies, it will be interesting to see whether this is a route industry explores.

Conclusion

The launch in recent years of a number of advanced cell and gene therapies with blockbuster price tags has heralded a new era for drug pricing and associated payment and reimbursement issues. It is a trend that looks likely to continue if current pipelines can also deliver much anticipated advanced therapies for common conditions. The high prices associated with these products present a myriad of issues however, not only for patients, payers and healthcare providers, but also for the licensors of the underlying intellectual property underpinning such treatments as industry adopts innovative new payment and reimbursement models which may impact on royalty streams.

When negotiating a licence to technology underpinning a cell or gene therapy the parties should consider how less conventional pricing mechanisms may impact the royalty structure. However, while there are some issues licensees and licensors may be able to consider upfront, it is difficult to anticipate the issues that may become relevant at a stage where pricing models have not been set, particularly as there is no one-size-fits-all pricing approach.

We have proposed an increased use of robust governance processes in a licensing relationship as one option to consider. It will also be interesting to see whether any trends emerge in relation to upfront and milestone payments in response to the challenges outlined above. In particular, licensees may push for more back-loaded or performance-related milestone payments to reflect the risks associated with pricing models which take a longer term view of the cost benefits of these types of therapies. We look forward to seeing what innovative approaches licensors and licensees adopt to adapt to these challenges in the years to come.

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Cell and gene therapies - Lexology

Bicoastal startup Kriya Therapeutics to grow gene therapy manufacturing in NC – WRAL Tech Wire

RESEARCH TRIANGLE PARK Theres a new biotech company setting up shop in the Triangle, and its flush with cash and headed up by some big names in the industry.

MeetKriya Therapeutics the brainchild of Dr. Shankar Ramaswamy, former chief business officer for Axovant Gene Therapies; Fraser Wright, co-founder of Sparks Therapeutics; and Roger Jeffs, the former United Therapeutics CEO who has deep rootsinNorth Carolina.

Launched in 2019, the biotech startup has dual headquarters in Durham and Palo Alto, California, and is billing itself as a next-generation gene therapy company focused on designing and developing treatments for highly prevalent and severe chronic conditions, like diabetes and obesity.

Earlier this month, it arrived in a big way after securing $80.5 million in Series A financing during a pandemic.

Its never easy. But itsa really significant pool of capital for us so were thankful to have been able to get it done,Ramaswamy, Kriyas CEO, told NC Biotech in a video interview this week.[Our] investors have a very long term vision of what a next generation gene therapy company could look like, and were very supportive building towards that vision.

Fraser Wright, PhDScientific Co-Founder and Chief Scientific Advisor; Shankar Ramaswamy, MDCo-Founder, Chairman, and CEO; and Nachi Gupta, MD, PhDChief of Staff.

Among the investors: QVT, Dexcel Pharma, Foresite Capital, Bluebird Ventures (associated with Sutter Hill Ventures), Narya Capital, Amplo,Paul Manning, andAsia Alpha. The round followed an initial seed financing led by Transhuman Capital late last year.

Itsis amilestone for the company andsets us up for success to goout and execute on the things that we really want to get done.

Ramaswamy says the company is now ready to scale, and is focused on building out its teams on both coasts.

We expect to grow very quickly both here in the Bay Area and in North Carolina, he said, emphasizing the Triangles importance as its manufacturing hub. That could be dozens of employees [here] in the not so distant future, if not larger over time.

How it will work: co-founders Ramaswamy and Wright will be based in the Bay area along with finance operations and early-stage research.

Meanwhile, in Durham, co-founder Jeffs will lead a team focused on development and manufacturing. It will include Britt Petty, AveXis former head of global manufacturing and Melissa Rhodes, former chief development officer at Altavant Sciences; and Mitch Lower, another Avexis veteran.

I dont view North Carolina as a satellite office.Thats where well be building our internal manufacturing infrastructure to solve for one of the key bottlenecks in gene therapy,which is manufacturing capacity and quality, saidRamaswamy.

Theres a very strong pool of talent in North Carolina, especially in biologics manufacturing. And [our team] has a very strong track record and history of success with biologics manufacturing, and strong experience there as well. So we think its a great place to be, given the past couple of decades, where there have been so many successful products actually manufactured in North Carolina.

Already, Kriyahas a number of gene therapies in the pipeline.

Among them: KT-A112, an investigational gene therapy administered by intramuscular injection that delivers the genes to produce insulin and glucokinase for type 1 and type 2 diabetes;KT-A522, an investigational gene therapy administered by salivary gland injection that delivers the gene to produce a glucagon-like peptide 1 (GLP-1) receptor agonist for type 2 diabetes and severe obesity; andKT-A83, an investigational gene therapy administered by intrapancreatic injection that delivers the gene to produce modified insulin growth factor 1 (IGF-1) for type 1 diabetes.

The team is currently set up in a temporary office in Durham, but plans to move intoamore permanent space somewhere in the Research Triangle in the near future.

Kriya is building a leading team and cutting-edge infrastructure to engineer best-in-class gene therapies for severe chronic conditions and accelerate their advancement into human clinical trials, saidJeffs, its vice chairman. Through its R&D laboratory capabilities in the Bay Area and in-house process development and manufacturing infrastructure inResearch Triangle Park, I believe that Kriya will be uniquely positioned to become a leader in the gene therapy field.

(c) North Carolina Biotechnology Center

Durhams Kriya Therapuetics lands $80M to advance gene therapies for diabetes, severe obesity

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Bicoastal startup Kriya Therapeutics to grow gene therapy manufacturing in NC - WRAL Tech Wire

Expression Therapeutics Announces IND Approval by the FDA for Hemophilia A Gene Therapy | DNA RNA and Cells | News Channels – PipelineReview.com

DetailsCategory: DNA RNA and CellsPublished on Tuesday, 26 May 2020 18:08Hits: 457

ATLANTA, GA, USA I May 26, 2020 I Expression Therapeutics has announced that it has received clearance by the United States Food and Drug Administration (FDA) to proceed following review of its Investigational New Drug Application (IND) for clinical testing of its novel lentiviral vector-based gene therapy ET3 for hemophilia A. Hemophilia A is the most common severe congenital bleeding disorder and afflicts approximately 1 in 8,000 people. Without treatment, severe hemophilia is crippling and fatal by late adolescence to early adulthood.

The ET3 gene therapy developed by Expression Therapeutics combines innovative platform technologies in protein bioengineering and tissue-directed expression. ET3 consists of autologous mobilized peripheral blood stem and progenitor cells transduced with a recombinant lentiviral vector, encoding a bioengineered coagulation factor VIII transgene designed for highlevel expression at low vector copy number. In the ET3 trial, subjects will be preconditioned with low-dose stem and immune cell suppressing agents prior to receiving a single infusion of ET3. The high-expression factor VIII can correct the bleeding tendency in hemophilia A. The duration of ET3 activity is expected to be the normal lifetime of the patient. Expression Therapeutics expects to initiate a Phase 1 clinical trial titled ET3-201 at Emory University and enroll patients shortly.

"We are extremely pleased that the FDA has granted permission to proceed with this clinical study," said Trent Spencer, Ph.D., President of Expression Therapeutics and Director of the Cell and Gene Therapy Program in the Aflac Cancer and Blood Disorders Center at Emory University.

Hematopoietic stem and progenitor cell lentiviral gene therapy is currently the only approach that offers the possibility of permanent cure of hemophilia A and provides an opportunity to reach both pediatric and adult populations.

"We are very excited to get the hemophilia A clinical trial underway, the first of six gene therapy products currently under development at Expression Therapeutics," said Mohan Rao, Ph.D., CEO of Expression Therapeutics.

Expression Therapeutics is a biotechnology company based in Atlanta. The current therapeutic pipeline includes advanced gene therapies for hemophilia A and B; neuroblastoma, T-cell leukemia/lymphoma, and acute myeloid leukemia (AML); and primary immunodeficiencies such as hemophagocytic lymphohistiocytosis (HLH).

SOURCE: Expression Therapeutics

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Expression Therapeutics Announces IND Approval by the FDA for Hemophilia A Gene Therapy | DNA RNA and Cells | News Channels - PipelineReview.com

Troubleshooting the Development of New Gene Therapies – Technology Networks

Gene therapy does more than treat genetic diseases it can cure them. A one-time dose of a non-replicative viral vector, such as commonly used recombinant adeno-associated virus (AAV), delivers a functional gene to replace or compensate for a dysfunctional version that is causing a patients disease (Figure 1). As a cutting-edge biopharmaceutical technology, there are multiple gene therapies now FDA approved; with hundreds more in clinical trials, were likely to see many more of these therapies on the market soon.1 However, to keep up with the rapid pace of clinical research, developers are working to streamline the manufacturing and quality control process to improve quality and lower the cost of bringing these important drugs to market.Developers use a multitude of analytical tests to develop gene therapies and optimize their manufacturing process. When developers get aberrant test results, they must be able to interpret where the problem lies. Did the manufacturing process produce an undesirable product, or is the analytical testing method unreliable? Analytical testing companies that have the infrastructure, personnel, and experience often partner with developers to tighten up analytical variability so that results of tests clearly indicate where there are opportunities to increase efficiency and product quality.

Figure 1. Gene delivery by recombinant viral vector.During gene therapy, viral capsids containing the therapeutic gene are taken up by the patients cells and the genetic material is delivered to the nucleus. There, the gene gets expressed as a protein necessary for the patients health. Credit: Avomeen.

Figure 2. A full AAV capsid and associated capsid impurities. Complete viral capsids have AAV are assembled from 60 capsid proteins, with a defined stoichiometry and shape and contain a therapeutic gene. AAV vector impurities include capsids that contain too many copies of the gene (overfilled), those that contain lower copy numbers or truncations of the gene (partially full), or empty capsids that contain no genetic material. Credit:Avomeen.

There are several ways to measure the empty/full capsid ratio, and as developers are establishing their chemistry, manufacturing and control (CMC) protocol, it is important that they choose an optimized method, as they must use that method for effective quality control from early process development to lot release and stability.3 Gene therapy developers may choose analytical ultracentrifugation to evaluate capsids, but while highly effective, this method is not as quantitative, robust or efficient as some newer methods. High-performance liquid chromatography (HPLC) using AAV full/empty analytical columns have been demonstrated to be highly effective at separating full, empty, and improperly filled capsids for robust quantification. Additionally, this method is higher throughput than ultracentrifugation, and requires less precious AAV sample to run.

Cellular potency is evaluated by transducing cells with the AAV product and then measuring a phenotypic or functional outcome due to the transduction. Developing these tests can be challenging because there is no one-size-fits-all test that will give developers the answers they need. Developers often draw on the experience of analytical labs to determine how to best evaluate their AAV products transduction efficiency.A gene therapy in development must also be tested to ensure that it is free of residual, process-related impurities such as polyethylenimine, iodixanol, poloxamer, and other excipients that must be removed in the final product to ensure safety. Few research and manufacturing facilities have the equipment and expertise necessary to perform this kind of testing, and it is advisable to find one that has experience testing polymers, extractables and leachables to examine if components of the manufacturing equipment or drugs packaging are not contaminating the final product.

As fast-paced as the gene therapy field is now, it stands to become a true race to the finish line to bring new gene therapies to market in the near future. Regulatory bodies are becoming more familiar with reviewing gene therapies, and the road to commercialization will move more quickly. There is no denying that gene therapies will bring incredible benefits to patients, but it will be crucial to improve manufacturing efficiency and lower costs to make gene therapies more accessible to the patients who need them.References

1. Colasante, W., Diesel, P., and Gerlovin, Lev. (2018). New Approaches To Market Access And Reimbursement For Gene And Cell Therapies. Cell & Gene. Retrieved from: https://www.cellandgene.com/doc/new-approaches-to-market-access-and-reimbursement-for-gene-and-cell-therapies-0001

2. Fraser Wright, J. (2014). Product-Related Impurities in Clinical-Grade Recombinant AAV Vectors: Characterization and Risk Assessment. Biomedicines, 2, 80-97; doi:10.3390/biomedicines2010080

3. U.S. Food & Drug Administration (2019). Guidance for Human Somatic Cell Therapy and Gene Therapy. Retrieved from: https://www.fda.gov/animal-veterinary/guidance-industry/chemistry-manufacturing-and-controls-cmc-guidances-industry-gfis

4. Stein, R. (2019). At $2.1 Million, New Gene Therapy Is The Most Expensive Drug Ever. NPR. Retrieved from: https://www.npr.org/sections/health-shots/2019/05/24/725404168/at-2-125-million-new-gene-therapy-is-the-most-expensive-drug-ever

5. Cohen, J.T, Chambers, J. D., Silver, M. C., Lin, P., Neumann, P.J. (2019). Putting The Costs And Benefits Of New Gene Therapies Into Perspective. Health Affairs. Retrieved from: https://www.healthaffairs.org/do/10.1377/hblog20190827.553404/full/

6. ATCC (accessed May, 2020) ATCC Virus Reference Materials. Retrieved from: https://www.atcc.org/en/Standards/Standards_Programs/ATCC_Virus_Reference_Materials.aspx#

7. U.S. FDA (2020). FDA Details Policies on Gene Therapies in Seven Guidances. Retrieved from: https://www.fdanews.com/articles/195767-fda-details-policies-on-gene-therapies-in-seven-guidances

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Lab Mice Shed Fat and Build Muscle with Gene Therapy – The Great Courses Daily News

By Jonny Lupsha, News Writer

According to the Fierce Biotech article, the mice who underwent the new gene therapy were injected with a gene that makes the protein follistatin, which in turn blocks a protein called myostatin. Myostatin regulates muscle growth. The therapy caused a significant buildup of muscle mass in the mice while also preventing obesity, the article said. The mice didnt just build muscle; they also nearly doubled their strength without exercising any more than they usually did. Despite being fed a high-fat diet, they had fewer metabolic issues and stronger hearts than did animals that did not receive the follistatin gene.

Scientists have been developing gene therapy for many years. It can change our bodies in many ways, and has potential serving as a treatment for cancer and muscular dystrophy.

The procedure that the mice underwent encapsulates what gene therapy isalthough scientists generally focus on people.

I define [gene therapy] as the addition of genes to humans for medical purposes, said Dr. David Sadava, Adjunct Professor of Cancer Cell Biology at the City of Hope Medical Center.

Dr. Sadava said gene therapy is based on four assumptions. First, whoever is doing the gene therapy has to know the gene thats involved in whichever problem needs to be treated. Second, they must have a normal, healthy copy of that gene available in the lab. Third, they must know where and when the gene is normally expressed. Finally, they have to be fairly certain what will happen when the gene is expressed normally.

Additionally, gene therapy must do several things in order to be considered successful.

First, gene therapy must get the gene into the appropriate cells, Dr. Sadava said. Second, gene therapy must get the gene expressed in those cells. Third, we have to get the gene integrated into the genome of the target cells so itll be there permanently. And fourth, you better not have any bad side effects to gene therapy, like any therapy in medicine.

According to Dr. Sadava, one kind of gene therapy is referred to as gene augmentation, and it comes into play when the functional product of a gene has been lost and no longer gets produced normally. By injecting a gene into someone, healthy copies of a protein product will be made and function restored.

We could hypothetically think of muscular dystrophy as a good target for gene therapy, he said. We know that muscles lack the protein dystrophinits an organizing proteinso well put in the good gene for good dystrophin.

Another kind of gene therapy is called target cell killing. Dr. Sadava said it uses a gene that either produces a poison that kills certain types of cells or it stimulates the immune system to do so. Target cell killing can be applied to cancer.

A gene is put into cancer cells that allows them to produce a protein that will make a toxic drug from a harmless chemical, Dr. Sadava said. So the idea is we inject a harmless chemical into the body, it goes all over the body and when it enters a tumor cell, its converted into a poison by the gene product of the gene that weve put in for gene therapy. So we might put in a gene that will cause a protein to be made that attracts killer T cells so the tumor will stick up its hand and say Come kill me now.'

Gene therapy is an exciting field in science and medicine with a lot of potential for humans. For now, it may seem like its just helping some overweight mice get a confidence boost, but the practical applications should shore up within our lifetime.

Dr. David Sadava contributed to this article. Dr. Sadava is Adjunct Professor of Cancer Cell Biology at the City of Hope Medical Center in Duarte, CA, and the Pritzker Family Foundation Professor of Biology, Emeritus, at The Claremont Colleges. Professor Sadava graduated from Carleton University with a B.S. with first-class honors in biology and chemistry. He earned a Ph.D. in Biology from the University of California, San Diego.

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Lab Mice Shed Fat and Build Muscle with Gene Therapy - The Great Courses Daily News

Reversing SHANK3 mutations in mice mitigates autism-like traits – Spectrum

Double dose: Mice with mutations in both copies of SHANK3 have more behavioral differences than animals with mutations in one copy of the gene.

tiripero / iStock

Correcting a mutation in the autism gene SHANK3 in fetal mice lessens some autism-like behaviors after birth, according to a new study1. The work adds to evidence that gene therapy may help some people with SHANK3 mutations.

In people, mutations in SHANK3 can lead to Phelan-McDermid syndrome, a condition that causes developmental delays and often autism. Up to 2 percent of people with autism have a mutation in SHANK32.

Our findings imply that early genetic correction of SHANK3 has the potential to provide therapeutic benefit for patients, lead investigator Craig Powell, professor of neurobiology at the University of Alabama at Birmingham, wrote in an email.

A 2016 study showed that correcting mutations in SHANK3 in both young and adult mice can decrease excessive grooming, which is thought to correspond to repetitive behaviors in people with autism.

Last year, Powell and his team also showed that correcting SHANK3 mutations in adult mice eliminates some autism-like behaviors3. But the results were difficult to interpret. The team reversed the mutation using an enzyme called Cre-recombinase that could edit SHANK3 if the animals were given a drug called tamoxifen. Control mice in that study that did not receive tamoxifen but had the gene for Cre still showed behavior changes, raising the possibility that the enzyme affected their brains.

In the new work, Powells team used a different approach. They engineered mice with a mutation in both or only one copy of SHANK3 the latter more closely mirrors what happens in people. Some animals had the Cre gene, but some also had another gene for a Cre-activating protein that is naturally expressed when the animals are in utero. By using this protein, the researchers could avoid using tamoxifen, which some studies have shown may also cause behavioral changes in mice4.

The control mice had either the gene for Cre-recombinase or fortheCre-activating protein, but not both, allowing the researchers to isolate any effects from the method itself.

They found that correcting the mutation lowers some but not all of the animals autism-like behaviors, a finding Powell says is surprising. The mice groom less and are more social by some measures, but they still prefer interacting with an object than with another mouse.

We dont really know why some behaviors are affected and not others, Powell says.

Mice with one mutated copy of SHANK3 have fewer behavioral differences than mice with two, they also found, which indicates the value of using both kinds of animals in gene-reversal studies, experts say.

The fact that they did analyze both side by side, and they did see some differences, I find quite intriguing, says Gaia Novarino, professor of neuroscience at the Institute of Science and Technology in Klosterneuburg, Austria.

The team originally planned to consider when and where in the brain SHANK3 was corrected. But the Cre-activating protein involved in the study was expressed throughout the brain, preventing region-specific findings.

The team gave some mice the antibiotic doxycycline to suppress Cre expression, in hopes of also testing the effects of correcting SHANK3 in adulthood. But the method failed, for unknown reasons.

It is also important to publish experiments that do not work out exactly as planned, Powell says.

The teams openness about the studys shortcomings could help others design their own studies or re-evaluate previous work, says Yong-Hui Jiang, chief of medical genetics at Yale University.

People will learn from the difficulties and the experience, Jiang says.

It would still be helpful to test whether correcting SHANK3 mutations can reverse autism-like behaviors in adult mice without using tamoxifen, other researchers say.

Its beneficial to do experiments in such a way where you leave very little room for alternative interpretations, says Gavin Rumbaugh, professor of neuroscience at the Scripps Research Institute in Jupiter, Florida. He suggests using a mouse that does not express Cre until the animal is administered doxycycline, rather than trying to suppress Cre with the drug.

The work lends credence to the idea that gene therapy might alleviate some difficulties associated with autism in people with SHANK3 mutations, researchers say. Further studies could also investigate in how many cells the gene needs to be restored to change behavior, and what would be the safest and most effective stage of development to intervene with a gene therapy.

The impression is you have a quite large window, Novarino says. Thats quite positive.

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Reversing SHANK3 mutations in mice mitigates autism-like traits - Spectrum

Orchard Therapeutics to Present at Virtual Investor Conferences in June – Yahoo Finance UK

BOSTON and LONDON, May 27, 2020 (GLOBE NEWSWIRE) -- Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader, today announced that presentations by the management team will be made at the following investor conferences in June:

Live webcasts of the presentations will be available under "News & Events" in the Investors & Media section of the company's website at http://www.orchard-tx.com. Webcast replays will be archived on the Orchard website following the presentation.

About OrchardOrchard Therapeuticsis a global gene therapy leader dedicated to transforming the lives of people affected by rare diseases through the development of innovative, potentially curative gene therapies. Ourex vivoautologous gene therapy approach harnesses the power of genetically modified blood stem cells and seeks to correct the underlying cause of disease in a single administration. In 2018, Orchard acquired GSKs rare disease gene therapy portfolio, which originated from a pioneering collaboration between GSK and theSan Raffaele Telethon Institute for Gene Therapy inMilan, Italy. Orchard now has one of the deepest and most advanced gene therapy product candidate pipelines in the industry spanning multiple therapeutic areas where the disease burden on children, families and caregivers is immense and current treatment options are limited or do not exist.

Orchard has its global headquarters inLondonandU.S.headquarters inBoston. For more information, please visitwww.orchard-tx.com, and follow us onTwitterandLinkedIn.

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

Contacts

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

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Orchard Therapeutics to Present at Virtual Investor Conferences in June - Yahoo Finance UK

Gene Therapy market worldwide is projected to grow by US$3.3 Billion – GlobeNewswire

New York, May 22, 2020 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "Global Gene Therapy Industry" - https://www.reportlinker.com/p05817594/?utm_source=GNW Poised to reach over US$125.3 Million by the year 2025, Lentivirus will bring in healthy gains adding significant momentum to global growth.

- Representing the developed world, the United States will maintain a 30% growth momentum. Within Europe, which continues to remain an important element in the world economy, Germany will add over US$133.3 Million to the regions size and clout in the next 5 to 6 years. Over US$117.2 Million worth of projected demand in the region will come from Rest of Europe markets. In Japan, Lentivirus will reach a market size of US$6.5 Million by the close of the analysis period. As the worlds second largest economy and the new game changer in global markets, China exhibits the potential to grow at 39.2% over the next couple of years and add approximately US$797 Million in terms of addressable opportunity for the picking by aspiring businesses and their astute leaders. Presented in visually rich graphics are these and many more need-to-know quantitative data important in ensuring quality of strategy decisions, be it entry into new markets or allocation of resources within a portfolio. Several macroeconomic factors and internal market forces will shape growth and development of demand patterns in emerging countries in Asia-Pacific, Latin America and the Middle East. All research viewpoints presented are based on validated engagements from influencers in the market, whose opinions supersede all other research methodologies.

Read the full report: https://www.reportlinker.com/p05817594/?utm_source=GNW

GENE THERAPY MCP-1MARKET ANALYSIS, TRENDS, AND FORECASTS, MAY 2CONTENTS

I. INTRODUCTION, METHODOLOGY & REPORT SCOPE

II. EXECUTIVE SUMMARY

1. MARKET OVERVIEW Global Competitor Market Shares Gene Therapy Competitor Market Share Scenario Worldwide (in %): 2019 & 2028 Impact of Covid-19 and a Looming Global Recession 2. FOCUS ON SELECT PLAYERS 3. MARKET TRENDS & DRIVERS 4. GLOBAL MARKET PERSPECTIVE Table 1: Gene Therapy Global Market Estimates and Forecasts in US$ Thousand by Region/Country: 2020-2027 Table 2: Gene Therapy Global Retrospective Market Scenario in US$ Thousand by Region/Country: 2012-2019 Table 3: Gene Therapy Market Share Shift across Key Geographies Worldwide: 2012 VS 2020 VS 2027 Table 4: Lentivirus (Vector) World Market by Region/Country in US$ Thousand: 2020 to 2027 Table 5: Lentivirus (Vector) Historic Market Analysis by Region/Country in US$ Thousand: 2012 to 2019 Table 6: Lentivirus (Vector) Market Share Breakdown of Worldwide Sales by Region/Country: 2012 VS 2020 VS 2027 Table 7: AAV (Vector) Potential Growth Markets Worldwide in US$ Thousand: 2020 to 2027 Table 8: AAV (Vector) Historic Market Perspective by Region/Country in US$ Thousand: 2012 to 2019 Table 9: AAV (Vector) Market Sales Breakdown by Region/Country in Percentage: 2012 VS 2020 VS 2027 Table 10: RetroVirus & Gamma RetroVirus (Vector) Geographic Market Spread Worldwide in US$ Thousand: 2020 to 2027 Table 11: RetroVirus & Gamma RetroVirus (Vector) Region Wise Breakdown of Global Historic Demand in US$ Thousand: 2012 to 2019 Table 12: RetroVirus & Gamma RetroVirus (Vector) Market Share Distribution in Percentage by Region/Country: 2012 VS 2020 VS 2027 Table 13: Modified Herpes Simplex Virus (Vector) World Market Estimates and Forecasts by Region/Country in US$ Thousand: 2to 2027 Table 14: Modified Herpes Simplex Virus (Vector) Market Historic Review by Region/Country in US$ Thousand: 2012 to 2019 Table 15: Modified Herpes Simplex Virus (Vector) Market Share Breakdown by Region/Country: 2012 VS 2020 VS 2027 Table 16: Adenovirus (Vector) World Market by Region/Country in US$ Thousand: 2020 to 2027 Table 17: Adenovirus (Vector) Historic Market Analysis by Region/Country in US$ Thousand: 2012 to 2019 Table 18: Adenovirus (Vector) Market Share Distribution in Percentage by Region/Country: 2012 VS 2020 VS 2027 Table 19: Other Applications (Vector) World Market Estimates and Forecasts in US$ Thousand by Region/Country: 2020 to 2027 Table 20: Other Applications (Vector) Market Worldwide Historic Review by Region/Country in US$ Thousand: 2012 to 2019 Table 21: Other Applications (Vector) Market Percentage Share Distribution by Region/Country: 2012 VS 2020 VS 2027 III. MARKET ANALYSIS GEOGRAPHIC MARKET ANALYSIS UNITED STATES Market Facts & Figures US Gene Therapy Market Share (in %) by Company: 2019 & 2025 Market Analytics Table 22: United States Gene Therapy Market Estimates and Projections in US$ Thousand by Vector: 2020 to 2027 Table 23: Gene Therapy Market in the United States by Vector: A Historic Review in US$ Thousand for 2012-2019 Table 24: United States Gene Therapy Market Share Breakdown by Vector: 2012 VS 2020 VS 2027 CANADA Table 25: Canadian Gene Therapy Market Estimates and Forecasts in US$ Thousand by Vector: 2020 to 2027 Table 26: Canadian Gene Therapy Historic Market Review by Vector in US$ Thousand: 2012-2019 Table 27: Gene Therapy Market in Canada: Percentage Share Breakdown of Sales by Vector for 2012, 2020, and 2027 JAPAN Table 28: Japanese Market for Gene Therapy: Annual Sales Estimates and Projections in US$ Thousand by Vector for the Period 2020-2027 Table 29: Gene Therapy Market in Japan: Historic Sales Analysis in US$ Thousand by Vector for the Period 2012-2019 Table 30: Japanese Gene Therapy Market Share Analysis by Vector: 2012 VS 2020 VS 2027 CHINA Table 31: Chinese Gene Therapy Market Growth Prospects in US$ Thousand by Vector for the Period 2020-2027 Table 32: Gene Therapy Historic Market Analysis in China in US$ Thousand by Vector: 2012-2019 Table 33: Chinese Gene Therapy Market by Vector: Percentage Breakdown of Sales for 2012, 2020, and 2027 EUROPE Market Facts & Figures European Gene Therapy Market: Competitor Market Share Scenario (in %) for 2019 & 2025 Market Analytics Table 34: European Gene Therapy Market Demand Scenario in US$ Thousand by Region/Country: 2020-2027 Table 35: Gene Therapy Market in Europe: A Historic Market Perspective in US$ Thousand by Region/Country for the Period 2012-2019 Table 36: European Gene Therapy Market Share Shift by Region/Country: 2012 VS 2020 VS 2027 Table 37: European Gene Therapy Market Estimates and Forecasts in US$ Thousand by Vector: 2020-2027 Table 38: Gene Therapy Market in Europe in US$ Thousand by Vector: A Historic Review for the Period 2012-2019 Table 39: European Gene Therapy Market Share Breakdown by Vector: 2012 VS 2020 VS 2027 FRANCE Table 40: Gene Therapy Market in France by Vector: Estimates and Projections in US$ Thousand for the Period 2020-2027 Table 41: French Gene Therapy Historic Market Scenario in US$ Thousand by Vector: 2012-2019 Table 42: French Gene Therapy Market Share Analysis by Vector: 2012 VS 2020 VS 2027 GERMANY Table 43: Gene Therapy Market in Germany: Recent Past, Current and Future Analysis in US$ Thousand by Vector for the Period 2020-2027 Table 44: German Gene Therapy Historic Market Analysis in US$ Thousand by Vector: 2012-2019 Table 45: German Gene Therapy Market Share Breakdown by Vector: 2012 VS 2020 VS 2027 ITALY Table 46: Italian Gene Therapy Market Growth Prospects in US$ Thousand by Vector for the Period 2020-2027 Table 47: Gene Therapy Historic Market Analysis in Italy in US$ Thousand by Vector: 2012-2019 Table 48: Italian Gene Therapy Market by Vector: Percentage Breakdown of Sales for 2012, 2020, and 2027 UNITED KINGDOM Table 49: United Kingdom Market for Gene Therapy: Annual Sales Estimates and Projections in US$ Thousand by Vector for the Period 2020-2027 Table 50: Gene Therapy Market in the United Kingdom: Historic Sales Analysis in US$ Thousand by Vector for the Period 2012-2019 Table 51: United Kingdom Gene Therapy Market Share Analysis by Vector: 2012 VS 2020 VS 2027 SPAIN Table 52: Spanish Gene Therapy Market Estimates and Forecasts in US$ Thousand by Vector: 2020 to 2027 Table 53: Spanish Gene Therapy Historic Market Review by Vector in US$ Thousand: 2012-2019 Table 54: Gene Therapy Market in Spain: Percentage Share Breakdown of Sales by Vector for 2012, 2020, and 2027 RUSSIA Table 55: Russian Gene Therapy Market Estimates and Projections in US$ Thousand by Vector: 2020 to 2027 Table 56: Gene Therapy Market in Russia by Vector: A Historic Review in US$ Thousand for 2012-2019 Table 57: Russian Gene Therapy Market Share Breakdown by Vector: 2012 VS 2020 VS 2027 REST OF EUROPE Table 58: Rest of Europe Gene Therapy Market Estimates and Forecasts in US$ Thousand by Vector: 2020-2027 Table 59: Gene Therapy Market in Rest of Europe in US$ Thousand by Vector: A Historic Review for the Period 2012-2019 Table 60: Rest of Europe Gene Therapy Market Share Breakdown by Vector: 2012 VS 2020 VS 2027 ASIA-PACIFIC Table 61: Asia-Pacific Gene Therapy Market Estimates and Forecasts in US$ Thousand by Region/Country: 2020-2027 Table 62: Gene Therapy Market in Asia-Pacific: Historic Market Analysis in US$ Thousand by Region/Country for the Period 2012-2019 Table 63: Asia-Pacific Gene Therapy Market Share Analysis by Region/Country: 2012 VS 2020 VS 2027 Table 64: Gene Therapy Market in Asia-Pacific by Vector: Estimates and Projections in US$ Thousand for the Period 2020-2027 Table 65: Asia-Pacific Gene Therapy Historic Market Scenario in US$ Thousand by Vector: 2012-2019 Table 66: Asia-Pacific Gene Therapy Market Share Analysis by Vector: 2012 VS 2020 VS 2027 AUSTRALIA Table 67: Gene Therapy Market in Australia: Recent Past, Current and Future Analysis in US$ Thousand by Vector for the Period 2020-2027 Table 68: Australian Gene Therapy Historic Market Analysis in US$ Thousand by Vector: 2012-2019 Table 69: Australian Gene Therapy Market Share Breakdown by Vector: 2012 VS 2020 VS 2027 INDIA Table 70: Indian Gene Therapy Market Estimates and Forecasts in US$ Thousand by Vector: 2020 to 2027 Table 71: Indian Gene Therapy Historic Market Review by Vector in US$ Thousand: 2012-2019 Table 72: Gene Therapy Market in India: Percentage Share Breakdown of Sales by Vector for 2012, 2020, and 2027 SOUTH KOREA Table 73: Gene Therapy Market in South Korea: Recent Past, Current and Future Analysis in US$ Thousand by Vector for the Period 2020-2027 Table 74: South Korean Gene Therapy Historic Market Analysis in US$ Thousand by Vector: 2012-2019 Table 75: Gene Therapy Market Share Distribution in South Korea by Vector: 2012 VS 2020 VS 2027 REST OF ASIA-PACIFIC Table 76: Rest of Asia-Pacific Market for Gene Therapy: Annual Sales Estimates and Projections in US$ Thousand by Vector for the Period 2020-2027 Table 77: Gene Therapy Market in Rest of Asia-Pacific: Historic Sales Analysis in US$ Thousand by Vector for the Period 2012-2019 Table 78: Rest of Asia-Pacific Gene Therapy Market Share Analysis by Vector: 2012 VS 2020 VS 2027 LATIN AMERICA Table 79: Latin American Gene Therapy Market Trends by Region/Country in US$ Thousand: 2020-2027 Table 80: Gene Therapy Market in Latin America in US$ Thousand by Region/Country: A Historic Perspective for the Period 2012-2019 Table 81: Latin American Gene Therapy Market Percentage Breakdown of Sales by Region/Country: 2012, 2020, and 2027 Table 82: Latin American Gene Therapy Market Growth Prospects in US$ Thousand by Vector for the Period 2020-2027 Table 83: Gene Therapy Historic Market Analysis in Latin America in US$ Thousand by Vector: 2012-2019 Table 84: Latin American Gene Therapy Market by Vector: Percentage Breakdown of Sales for 2012, 2020, and 2027 ARGENTINA Table 85: Argentinean Gene Therapy Market Estimates and Forecasts in US$ Thousand by Vector: 2020-2027 Table 86: Gene Therapy Market in Argentina in US$ Thousand by Vector: A Historic Review for the Period 2012-2019 Table 87: Argentinean Gene Therapy Market Share Breakdown by Vector: 2012 VS 2020 VS 2027 BRAZIL Table 88: Gene Therapy Market in Brazil by Vector: Estimates and Projections in US$ Thousand for the Period 2020-2027 Table 89: Brazilian Gene Therapy Historic Market Scenario in US$ Thousand by Vector: 2012-2019 Table 90: Brazilian Gene Therapy Market Share Analysis by Vector: 2012 VS 2020 VS 2027 MEXICO Table 91: Gene Therapy Market in Mexico: Recent Past, Current and Future Analysis in US$ Thousand by Vector for the Period 2020-2027 Table 92: Mexican Gene Therapy Historic Market Analysis in US$ Thousand by Vector: 2012-2019 Table 93: Mexican Gene Therapy Market Share Breakdown by Vector: 2012 VS 2020 VS 2027 REST OF LATIN AMERICA Table 94: Rest of Latin America Gene Therapy Market Estimates and Projections in US$ Thousand by Vector: 2020 to 2027 Table 95: Gene Therapy Market in Rest of Latin America by Vector: A Historic Review in US$ Thousand for 2012-2019 Table 96: Rest of Latin America Gene Therapy Market Share Breakdown by Vector: 2012 VS 2020 VS 2027 MIDDLE EAST Table 97: The Middle East Gene Therapy Market Estimates and Forecasts in US$ Thousand by Region/Country: 2020-2027 Table 98: Gene Therapy Market in the Middle East by Region/Country in US$ Thousand: 2012-2019 Table 99: The Middle East Gene Therapy Market Share Breakdown by Region/Country: 2012, 2020, and 2027 Table 100: The Middle East Gene Therapy Market Estimates and Forecasts in US$ Thousand by Vector: 2020 to 2027 Table 101: The Middle East Gene Therapy Historic Market by Vector in US$ Thousand: 2012-2019 Table 102: Gene Therapy Market in the Middle East: Percentage Share Breakdown of Sales by Vector for 2012,2020, and 2027 IRAN Table 103: Iranian Market for Gene Therapy: Annual Sales Estimates and Projections in US$ Thousand by Vector for the Period 2020-2027 Table 104: Gene Therapy Market in Iran: Historic Sales Analysis in US$ Thousand by Vector for the Period 2012-2019 Table 105: Iranian Gene Therapy Market Share Analysis by Vector: 2012 VS 2020 VS 2027 ISRAEL Table 106: Israeli Gene Therapy Market Estimates and Forecasts in US$ Thousand by Vector: 2020-2027 Table 107: Gene Therapy Market in Israel in US$ Thousand by Vector: A Historic Review for the Period 2012-2019 Table 108: Israeli Gene Therapy Market Share Breakdown by Vector: 2012 VS 2020 VS 2027 SAUDI ARABIA Table 109: Saudi Arabian Gene Therapy Market Growth Prospects in US$ Thousand by Vector for the Period 2020-2027 Table 110: Gene Therapy Historic Market Analysis in Saudi Arabia in US$ Thousand by Vector: 2012-2019 Table 111: Saudi Arabian Gene Therapy Market by Vector: Percentage Breakdown of Sales for 2012, 2020, and 2027 UNITED ARAB EMIRATES Table 112: Gene Therapy Market in the United Arab Emirates: Recent Past, Current and Future Analysis in US$ Thousand by Vector for the Period 2020-2027 Table 113: United Arab Emirates Gene Therapy Historic Market Analysis in US$ Thousand by Vector: 2012-2019 Table 114: Gene Therapy Market Share Distribution in United Arab Emirates by Vector: 2012 VS 2020 VS 2027 REST OF MIDDLE EAST Table 115: Gene Therapy Market in Rest of Middle East: Recent Past, Current and Future Analysis in US$ Thousand by Vector for the Period 2020-2027 Table 116: Rest of Middle East Gene Therapy Historic Market Analysis in US$ Thousand by Vector: 2012-2019 Table 117: Rest of Middle East Gene Therapy Market Share Breakdown by Vector: 2012 VS 2020 VS 2027 AFRICA Table 118: African Gene Therapy Market Estimates and Projections in US$ Thousand by Vector: 2020 to 2027 Table 119: Gene Therapy Market in Africa by Vector: A Historic Review in US$ Thousand for 2012-2019 Table 120: African Gene Therapy Market Share Breakdown by Vector: 2012 VS 2020 VS 2027 IV. COMPETITION

Total Companies Profiled: 98 Read the full report: https://www.reportlinker.com/p05817594/?utm_source=GNW

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Original post:

Gene Therapy market worldwide is projected to grow by US$3.3 Billion - GlobeNewswire

Generation Bio tees up $125M IPO to push next-gen gene therapies – FierceBiotech

Another preclinical-stage biotech is taking to the public marketsGeneration Bio filed for a $125 million IPO to advance a pair of gene therapies for liver disease and push one of them into the clinic.

The deal comes on the heels of a $110 million venture round tagged to bankroll its lead programs: liver-targeted therapies for hemophilia A and phenylketonuria (PKU). Together, the funds will allow Generation Bio to finish IND-enabling studies for both programs as well as kick off a clinical trial for one, according to a securities filing.

That phase 1 study is still a ways away, though: [All] of our programs are currently in the early stage of development, including our programs in PKU and hemophilia A, and we have not yet identified a product candidate for any of our programs, the company said in the filing.

ASCO Explained: Expert predictions and takeaways from the world's biggest cancer meeting

Join FiercePharma for our ASCO pre- and post-show webinar series. We'll bring together a panel of experts to preview what to watch for at ASCO. Cancer experts will highlight closely watched data sets to be unveiled at the virtual meeting--and discuss how they could change prescribing patterns. Following the meeting, well do a post-show wrap up to break down the biggest data that came out over the weekend, as well as the implications they could have for prescribers, patients and drugmakers.

RELATED: Generation Bio grabs a $110M round to ramp up work on next-gen gene therapies

Generation Bio plans to gather enough data to pick its candidates over the course of this year, with IND-enabling studies slated for 2021 and IND applications for 2022.

We anticipated submitting IND applications for additional programs in 2023 and beyond, the company said in the filing.

The companys pipeline includes treatments for diseases of the eye as well as three other liver disease programs, including treatments for Wilson disease and Gaucher disease. Its most advanced retina disease program targets Leber congenital amaurosis 10, or LCA10, a rare type of blindness caused by mutations in the CEP290 gene. Thats the same form of LCA that Editas Medicines and Allergan are aiming at with a CRISPR-based gene editing treatment.

RELATED: Editas, Allergan kick off long-awaited in vivo CRISPR trial

Generation Bios programs are based on its non-viral gene therapy platform that uses lipid nanoparticles to deliver closed-ended DNA (ceDNA) to diseased tissue.

Our vision is to develop re-dosable, long-lasting gene therapies manufactured at a scale that leaves no patient or family behind, said Geoff McDonough, M.D., president and CEO of Generation Bio, earlier this year.

See the article here:

Generation Bio tees up $125M IPO to push next-gen gene therapies - FierceBiotech

Expression Therapeutics Announces IND Approval by the FDA for Hemophilia A Gene Therapy – PRNewswire

ATLANTA, May 26, 2020 /PRNewswire/ -- Expression Therapeutics has announced that it has received clearance by the United States Food and Drug Administration (FDA) to proceed following review of its Investigational New Drug Application (IND) for clinical testing of its novel lentiviral vector-based gene therapy ET3 for hemophilia A. Hemophilia A is the most common severe congenital bleeding disorder and afflicts approximately 1 in 8,000 people. Without treatment, severe hemophilia is crippling and fatal by late adolescence to early adulthood.

The ET3 gene therapy developed by Expression Therapeutics combines innovative platform technologies in protein bioengineering and tissue-directed expression. ET3 consists of autologous mobilized peripheral blood stem and progenitor cells transduced with a recombinant lentiviral vector, encoding a bioengineered coagulation factor VIII transgene designed for highlevel expression at low vector copy number. In the ET3 trial, subjects will be preconditioned with low-dose stem and immune cell suppressing agents prior to receiving a single infusion of ET3. The high-expression factor VIII can correct the bleeding tendency in hemophilia A. The duration of ET3 activity is expected to be the normal lifetime of the patient. Expression Therapeutics expects to initiate a Phase 1 clinical trial titled ET3-201 at Emory University and enroll patients shortly.

"We are extremely pleased that the FDA has granted permission to proceed with this clinical study," said Trent Spencer, Ph.D., President of Expression Therapeutics and Director of the Cell and Gene Therapy Program in the Aflac Cancer and Blood Disorders Center at Emory University.

Hematopoietic stem and progenitor cell lentiviral gene therapy is currently the only approach that offers the possibility of permanent cure of hemophilia A and provides an opportunity to reach both pediatric and adult populations.

"We are very excited to get the hemophilia A clinical trial underway, the first of six gene therapy products currently under development at Expression Therapeutics," said Mohan Rao, Ph.D., CEO of Expression Therapeutics.

Expression Therapeutics is a biotechnology company based in Atlanta. The current therapeutic pipeline includes advanced gene therapies for hemophilia A and B; neuroblastoma, T-cell leukemia/lymphoma, and acute myeloid leukemia (AML); and primary immunodeficiencies such as hemophagocytic lymphohistiocytosis (HLH).

For inquiries, please contact:

Ashley WalshDirector of Corporate DevelopmentExpression Therapeutics 1860 Montreal RoadTucker, Georgia 30084[emailprotected]+1 312.637.2975

SOURCE Expression Therapeutics

http://www.expressiontherapeutics.com

Excerpt from:

Expression Therapeutics Announces IND Approval by the FDA for Hemophilia A Gene Therapy - PRNewswire

Novartis’ gene therapy approved in Europe, talks ongoing on price – BioPharma-Reporter.com

In March, Novartis was able to announce that Zolegensma (onasemnogene abeparvovec) that it had received a positive opinion on its application for marketing approval by the European Medicines Agency.

Yesterday this was followed up by the announcement that the European Commission (EC) had provided the gene therapy conditional approval for the treatment of patients with spinal muscular atrophy. The treatment will be available for those with a bi-allelic mutation in the SMN1 gene and a diagnosis of SMA type 1; or for patients with SMA with the mutation and up to three copies of the SMN2 gene.

The company added that the approval also covers babies and young children with SMA, up to a body weight of 21kg (46 pounds).

Novartis stated that the treatment will be made available immediately in France and that Germany would gain access shortly.

In terms of pricing, the company noted that it was working with stakeholder organizations across Europe, so that pricing would "work within existing, local pricing and reimbursement frameworks."

The pricing has proved a controversial aspect of the one-time gene therapy, which entered the US market at a cost of $2.1m (1.9m) per patient.

In its announcement, the company countered that the cost of caring for a child with SMA to the healthcare system is approximately 2.5m to 4m for 10 years of care.

In fourth quarter results, the treatment saw sales of $170m in the US.

Link:

Novartis' gene therapy approved in Europe, talks ongoing on price - BioPharma-Reporter.com

NOVASEP and LYSOGENE Announce their New Collaboration for Development and Production of GM1 Gangliosidosis Gene Therapy Product – Business Wire

LYON, France & PARIS--(BUSINESS WIRE)--Regulatory News:

Novasep, a leading supplier of services and technologies for the life sciences industry, and Lysogene (Paris:LYS)(FR0013233475 LYS), a phase 3 gene therapy platform company targeting central nervous system (CNS) diseases, today announced the signature of an agreement for the development and manufacturing of LYS-GM101, an AAVrh10-based gene therapy drug candidate for the treatment of GM1 Gangliosidosis, a rare neuronopathic lysosomal storage disorder.

With this collaboration, the two companies consolidate their long-lasting partnership initiated with the development and manufacturing of Lysogenes lead gene therapy product, LYS-SAF302, currently in clinical phase 2/3.

Mark Plavsic, Lysogenes Chief Technical Officer said: Following the successful relationship developed during the past 4 years, I am very pleased to continue working with Novasep, which is emerging as a true leader in gene therapy development and manufacturing. By extending our collaboration, we secure the clinical production of our experimental treatment for GM1 gangliosidosis and take an option for a smooth and effective technical transfer to a future commercial process.

Cedric Volanti, Novaseps President of Biopharma Solutions said: "We, at Novasep, are delighted to pursue and extend our partnership with Lysogene. Novasep will bring its expertise and mobilize its production capacities to first help Lysogene in the clinical development of its innovative gene therapy treatment for GM1 gangliosidosis; and secondly, to shorten the transition to a commercial product manufacturing by ensuring a smooth process transfer to our commercial manufacturing facility."

About Lysogene

Lysogene is a gene therapy company focused on the treatment of orphan diseases of the central nervous system (CNS). The company has built a unique capability to enable a safe and effective delivery of gene therapies to the CNS to treat lysosomal diseases and other genetic disorders of the CNS. A phase 2/3 clinical trial in MPS IIIA in partnership with Sarepta Therapeutics, Inc. is ongoing and a phase 1/3 clinical trial in GM1 gangliosidosis is in preparation. In accordance with the agreements signed between Lysogene and Sarepta Therapeutics, Inc., Sarepta Therapeutics, Inc. will hold exclusive commercial rights to LYS-SAF302 in the United States and markets outside Europe; and Lysogene will maintain commercial exclusivity of LYS-SAF302 in Europe. Lysogene is also collaborating with an academic partner to define the strategy of development for the treatment of Fragile X syndrome, a genetic disease related to autism. http://www.lysogene.com.

About Novasep

Novasep provides cost-effective and sustainable manufacturing solutions for the life sciences industries.

With 20 years experience in the development and manufacturing of biomolecules, Novasep offers a full range of CDMO services for:

- Viral vectors (AAV, Adenovirus, Lentivirus, HSV, VSV, VEEV) for cell and gene therapy, immunotherapy and vaccination, from process development to cGMP production

- Fill & Finish services for viral vectors, attenuated and live viruses, mAbs, plasmids and other biologics, from formulation to packaging

As part of its growth strategy Rise-2, Novasep recently unveiled a new facility, Senrise-IV, dedicated to the commercial production of viral vectors which has been completed last year by Senefill, a new Fill & Finish commercial facility for aseptic operations. Both facilities located in Seneffe, Belgium, will contribute to the success of biopharmaceuticals projects.

Read the rest here:

NOVASEP and LYSOGENE Announce their New Collaboration for Development and Production of GM1 Gangliosidosis Gene Therapy Product - Business Wire

Evox Therapeutics Appoints Martin Andrews as Non-Executive Director – BioSpace

Senior industry executive with specialist expertise in rare diseases

OXFORD, England, May 27, 2020 /PRNewswire/ -- Evox Therapeutics Ltd ('Evox' or the 'Company'), a leading exosome therapeutics company, is pleased to announce the appointment of Martin Andrews as a Non-Executive Director. Martin is a highly experienced senior pharmaceutical executive with broad R&D, commercial and operational experience, and has deep specialist expertise in rare diseases, gene therapy and vaccines.

Martin is an experienced Non-Executive Director and commercial leader, with a strong track record of strategy development and operational delivery. He has had a long and successful career at GlaxoSmithKline, where he has held many senior positions. Most recently, Martin was Senior Vice President, Rare Diseases. Here, he led the global rare disease business and oversaw the development of a portfolio of ex vivo gene therapies, and the launch of Strimvelis, the world's first life-saving gene therapy for children. Furthermore, under his leadership, GlaxoSmithKline transferred its gene therapy portfolio to Orchard Therapeutics. Prior to that, Martin was Senior Vice President, Global Vaccines Commercial, where he led the development of the growth strategy and transformation of the commercial capability in GlaxoSmithKline's Vaccines division.

Martin has previously held Board positions at Orchard Therapeutics and the Alliance for Regenerative Medicine. He is currently a Non-Executive Director of Freeline Therapeutics, where he brings his commercial expertise to their gene therapy portfolio of drugs.

Dr Antonin de Fougerolles, Chief Executive Officer of Evox, commented:

"We're very pleased to welcome Martin as a Non-Executive Director. With his rare disease drug development experience and strong track-record of commercial success, Martin will be a great asset to the company. His expertise will play an important role in helping guide our business growth."

Commenting on his appointment, Martin Andrews said:

"I'm delighted to be joining the Board of Evox. This is an exciting period for the Company and I believe its technology has the potential to transform how medicines are developed and delivered for patients with conditions that are not possible to treat adequately today, especially those with rare diseases. I am thrilled to be part of the team and look forward to contributing."

About Evox Therapeutics

Evox Therapeutics is a privately held, Oxford-based biotechnology company focused on harnessing and engineering the natural delivery capabilities of extracellular vesicles, known as exosomes, to develop an entirely new class of therapeutics. Backed by leading life sciences venture capital groups and supported by a comprehensive intellectual property portfolio, Evox's mission is to positively impact human health by creating novel exosome-based therapeutics for the treatment of various severe diseases with limited options for patients and their families. Evox has created substantial proprietary technology to modify exosomes using various molecular engineering, drug loading, and targeting strategies to facilitate targeted drug delivery to organs of interest, including the brain and the central nervous system. Exosome-based drugs have the potential to address some of the limitations of protein, antibody and nucleic acid-based therapies by enabling delivery to cells and tissues that are currently out of reach using other drug delivery technologies, and Evox is leading the development within this emerging therapeutic space.

For further information visit: http://www.evoxtherapeutics.com

View original content:http://www.prnewswire.com/news-releases/evox-therapeutics-appoints-martin-andrews-as-non-executive-director-301065071.html

SOURCE Evox Therapeutics

Originally posted here:

Evox Therapeutics Appoints Martin Andrews as Non-Executive Director - BioSpace

New Zolgensma ‘inflection point’ is here as Novartis snags EU nod for SMA gene therapy – FiercePharma

As the number of U.S. spinal muscular atrophy (SMA) patients Zolgensma treats each quarter stabilizes, Novartis is counting on a set of inflection points for future growth. Now, it has one.

After a manufacturing-related delay, Novartis has won conditional approval in the EU for the one-time gene therapy to treat patients with a clinical diagnosis of SMA type 1 and others with up to three copies of the SMN2 backup gene, the company said Monday.

Zolgensmas EU label is different from the U.S. version. While its approved by the FDA to treat children less than 2 years of age, the EMA allows it in babies and young children who weigh up to 21 kilograms. According to a Pediatric Neuromuscular Clinical Research natural history study of SMA, almost all patients under the age of 5 will be under 21 kg.

Understanding the Importance of Crystallization Processes to Avoid Unnecessary Cost, Risk and Development Delays

A well-developed crystallization process can produce suitable particles that can facilitate consistent filtration, drying and formulation of the API and allow confident and reliable manufacturing of the final drug product, while avoiding unnecessary cost, risk and development delays.

The number of SMN2 genes determines the severity of the disease, with SMA type 1 the most severe form. The U.S. approval is for all SMA types, but the EU nod leaves out a small proportion of patients who could develop mild, late-onset type 3 or type 4 SMA. Patients with type 3 SMA, sometimes called Kugelberg-Welander disease, may have up to four copies of SMN2.

The difference could havemixed effectson Zolgensmas opportunity in the two territories. For existing patients already on Biogens Spinraza, Zolgensma could steal share from older patients in the EU. But for new patients, the FDA label enables the Novartis drug to reach more patients if diagnosis through newborn screening is widely adopted and patients are treated early.

Zolgensma has reached a steady state where it treats about 100 patients per quarter in the U.S., Novartis CEO Vas Narasimhan recently told investors. That translated into $170 million sales in the first quarter, a slight quarter-over-quarterdecline due to COVID-19. The companys expecting approvals in new countriesand new indications to be inflection points that will eventually propel the drug to blockbuster sales.

RELATED:The top 10 drug launches since 2017 | 7. Zolgensma

It had the first point in March with a Japanese nod, also for patients under 2 years old. Last week, the Japanese government approved Zolgensmas price at 167 million yen ($1.55 million), lower than its U.S. list price of $2.12 million.

In Europe, final pricing and reimbursement decisions will be determined at the local level, a spokesperson at Novartis AveXis gene therapy unit told FiercePharma. Cumulative healthcare costs per SMA patient are estimated at between 2.5 million to 4 million over the first 10 years, the company said.

Novartis said its working with European countries local regulators on an access program called Day One. Its designed to provide fast access to Zolgensma even before national pricing and reimbursement agreements are in place, a process that sometimes takes years. The program offers several options such as deferred payments and installment over years as well as outcomes-based rebates. The drug has been made available in France under the countrys Temporary Authorization for Use pathway, and access is expected shortly in Germany, the Swiss drugmaker said.

Beyond the already-approved intravenous version, Novartis is developing a formulation that delivers Zolgensma through an injection into the spinal canal so that it can reach older patients up to 5 years of age in the U.S. Its working with the FDA to resolve a partial clinical hold slapped on the high dose of the intrathecal formulation before it can file for an approval.

Currently, AveXis makes Zolgensma at its site in Libertyville, Illinois. It also has plants in Durham, North Carolina, and Longmont, Colorado. The latter two are expected to be licensed in 2021, the company spokesperson said, adding that it has no plans for a manufacturing facility in the EU at this point.

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

European regulators accept FibroGen’s anemia drug for review; Passage Bio’s lead gene therapy gets more love from the FDA – Endpoints News

When a field that depends on scientific benchwork suddenly moves online, what happens to collaborations and the innovation supply chain? We are seeing the answer to this question play out in real time during the Covid-19 crisis. Across the United States and abroad, measures to safeguard against this serious disease have created an unplanned, massive test for remote work in biotechnology.

Scientific companies face a unique challenge during the shutdown: continuing their research. Lab-based work requires in-person, human attention, as many experiments are complex and require specialized expertise. These projects are often achieved through research collaborations between organizations, requiring meetings to share data, shared work environments, and deep discussions. And their results are priceless these collaborations have the potential to generate therapies that save or improve millions of lives in the future. This is why biotechnology companies have been deemed an essential industry and continue to operate in some form during the shutdown.

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European regulators accept FibroGen's anemia drug for review; Passage Bio's lead gene therapy gets more love from the FDA - Endpoints News

Gene therapy could help millions of ash trees fight deadly beetle Emerald Ash Borer – inews

NewsEnvironmentResearchers at Queen Mary University of London and the Royal Botanic Gardens, Kew, discovered genes that create chemicals harmful to insects

Monday, 25th May 2020, 11:22 pm

A set of genes has been identified that could protect ash trees from a deadly beetle, which attacks by burrowing into their stems.

Named the Emerald Ash Borer (EAB), the killer pest is expected to destroy hundreds of millions of trees worldwide in the years to come without any intervention.

Researchers at Queen Mary University of London and the Royal Botanic Gardens, Kew, discovered genes that create chemicals likely to be harmful to the insects.

They sequenced the genomes of 22 types of ash tree and used this information to analyse how the different species are related to each other.

Help trees fight deadly beetles

Meanwhile, the US Department of Agriculture Forest Service, in Ohio, tested the resistance of more than 20 ash species to EAB by hatching eggs on the bark of trees, and following the fate of the beetle larvae.

Resistant ash trees killed the larvae when they burrowed into their stems, but susceptible ones did not.

The scientists discovered 53 candidate resistance genes, several of which are involved in making chemicals that are likely to be harmful to insects.

The findings suggest that breeding or gene editing could be used to place these resistance genes into ash species currently affected by EAB.

Dr Laura Kelly, an academic visitor at Queen Mary and lead author of the study, published in the journal Nature Ecology & Evolution, said: Knowledge of genes involved in resistance will...help efforts to identify trees that are able to survive the ongoing threat from EAB, and in turn, could facilitate restoration of ash woodlands in areas which have already been invaded."

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Gene therapy could help millions of ash trees fight deadly beetle Emerald Ash Borer - inews

Generation Bio Leads a Trio of Biotech Companies Aiming for the Nasdaq – Xconomy

XconomyNational

COVID-19 has ravaged the economy, and it was expected to quash the IPO market, too. But the biotech sector is defying the pandemic with crossover financings and freshly minted public companies. On Friday, three firms added their names to the list of life science companies preparing to join the public markets.

Gene therapy company Generation Bio, vaccines developer Vaxcyte, and cancer diagnostics maker Burning Rock Biotech each filed IPO paperwork just ahead of the Memorial Day weekend. The filings come as an index of the largest and most liquid IPOs of the past two years reached an all-time high, according to Renaissance Capital. The IPO research firm says the indexs rise was led by Moderna (NASDAQ: MRNA), the Cambridge, MA-based biotech that this week released preliminary Phase 1 data for its experimental COVID-19 vaccine.

Investors are betting that new technologies and services are best suited for the post-pandemic world, Renaissance says.

Heres a look at the three new additions to the biotech IPO queue.

GENERATION BIO EYES NEXT-GEN GENE THERAPIES

Generation Bio aims to improve upon gene therapy with an alternative to the engineered viruses currently used to ferry these therapies into cells. Viral delivery has limitations that include safety risks and a relatively small genetic payload capacity, the Cambridge-based company says in its filing. Furthermore, if patients dont already have antibodies to the viruses, they develop them after their first dose, which means patients cant receive additional doses if the initial one doesnt work as expected or stops working over time. Gene therapies that employ viral delivery are also expensive to manufacture.

Instead of a virus as its delivery vehicle, Generation Bio uses a lipid nanoparticle (LNP). The LNP encapsulates its genetic payload, a DNA construct called closed-ended DNA. This approach permits an individualized approach to treatment as a patient can be redosed until reaching the level needed for effective treatment, the company says. The technology also has a greater payload capacity and its less expensive to manufacture at scale compared to viral gene therapies. Those differences will enable delivery of gene therapies to more types of tissue, which in turn will allow for the treatment of a broader range of diseases spanning more patients, Generation Bio says.

Generation Bios initial focus is developing gene therapies targeting diseases of the liver and the eye. The most advanced liver programs are for phenylketonuria (PKU), an inherited metabolic disorder, and hemophilia type A, the most common form of the bleeding disorder. For the eye, Generation Bio is developing a gene therapy for an inherited form of vision loss called Leber congenital amaurosis 10 (LCA10) and for Stargardt disease, which is a form of macular degeneration.

Those programs trail other experimental gene therapies that are currently in clinical testing. Pfizer (NYSE: PFE) is developing a hemophila A gene therapy that came from the labs of partner Sangamo Therapeutics (NASDAQ: SGMO). BioMarin Pharmaceutical (NASDASQ: BMRN) is testing gene therapies for hemophilia A and PKU. In LCA10,Editas Medicine (NASDAQ: EDIT) is developing a gene therapy under a partnership with Allergan, now a subsidiary of AbbVie (NYSE: ABBV). That therapeutic candidate uses the CRISPR gene-editing technology to correct the faulty gene inside the patient. All of these experimental gene therapies use adeno-associated viruses to reach their targets.

Generation Bio has raised more than $227 million, most recently a $110 million Series C financing in January. That funding round added crossover investors, whose involvement is viewed as an indication a company is preparing for an IPO. CEO Geoff McDonough acknowledged as much at the time, telling Xconomy he expected to take the company public in advance of beginning clinical trials. Other rare diseases that the company is exploring include Wilsons disease and Gaucher disease.

In its filing, Generation Bio set a preliminary $125 million target for its IPO. The company has applied for a Nasdaq listing under the stock symbol GBIO. At the end of the first quarter of this year, Generation Bio reported having $104.5 million in cash. The company says it plans to use the IPO proceeds to continue R&D, including the preclinical work to support an application to start clinical testing of one of its liver disease gene therapies.

Generation Bios largest shareholders are Jason Rhodes, the companys chairman and founding CEO, and Atlas Venture. Each holds a 37 percent pre-IPO stake, according to the filing. Fidelity Investment owns 14.9 percent of the company, followed by funds advised by T. Rowe Price, which hold 8.9 percent.

VAXCYTE SETS SIGHTS ON TOPPING A PFIZER VACCINE

Vaxcyte is the new name for SutroVax, which changed its moniker this week. The Foster City, CA-based company spun out of Sutro Biopharma, and it develops vaccines using technology licensed from its former parent. The company says in its IPO filing that its cell-free protein synthesis technology enables it to design protein carriers and antigensa vaccines key componentsthat are better than what can be produced using conventional vaccine technologies.

Pneumococcal bacteria, which can cause pneumonia and meningitis, are Vaxcytes first target. The top pneumococcal vaccine, a Pfizer (NYSE: PFE) product called Prevnar 13, is a blockbuster seller that protects against 13 of the more than 90 pneumococcal strains. Vaxcytes preclinical vaccine candidate, VAX-24, is being developed to address 24 strains.

The IPO filing comes two months after Vaxyte closed a $110 million Series D round that added crossover investors. The company says in the filing that it has raised about $282 million cumulatively. As of March 31, Vaxcytes cash holdings totaled $154.7 million. The companys largest shareholders include Abingworth Bioventures, Longitude Capial Management, and Roche Finance, though the percentages of those stakes were not disclosed.

Vaxcyte says it plans to apply for a Nasdaq listing under the stock symbol PCVX. The vaccine developer set a preliminary $100 million goal; proceeds will be used to complete preclinical development and advance VAX-24 into human testing. The cash will also finance manufacturing, as well as continued development of other vaccine candidates.

BURNING ROCK BIOTECH BLAZES A PATH TO NASDAQ

Burning Rock Biotech is based in China, where it sells next-generation sequencing products that help physicians select cancer treatments for their patients. Now its seeking a Nasdaq listing that will give US investors a chance to grab a stake.

The company says in its filing that it offers 13 tests spanning solid tumors including cancers of the lung, prostate, and breast, as well as blood cancers. In addition helping physicians treat cancer patients, Burning Rock says its products support clinical trials conducted by large pharmaceutical companies, including AstraZeneca (NYSE: AZN), Bayer, and Johnson & Johnson (NYSE: JNJ). The companys central laboratory processes biopsy samples from hospital patients as well as from its pharmaceutical partners. The central lab business is the companys largest business segment.

Burning Rock reported $53.9 million in 2019 revenue. For the first quarter of 2020, revenue was $9.5 million. The company set a preliminary $100 million goal for its IPO, and says it plans to apply for a Nasdaq listing under the stock symbol BNR. According to the filing, Burning Rock expects to use the IPO cash for research and development of early cancer detection technologies, as well as for seeking approvals in China for additional cancer therapy selection products.

Image: iStock/peterschreiber.media

Frank Vinluan is an Xconomy editor based in Research Triangle Park. You can reach him at fvinluan@xconomy.com.

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Generation Bio Leads a Trio of Biotech Companies Aiming for the Nasdaq - Xconomy

QPS Continues to Expand UPLC-HRMS Quantitation Capabilities to Support Gene Therapy and Protein Drug Development – PRNewswire

NEWARK, Delaware, May 19, 2020 /PRNewswire/ --QPS, a global contract research organization (CRO) that provides discovery, preclinical, and clinical drug development services, is reinforcing its focus on qualitative and quantitative bioanalysis of biotherapeutics. QPS announces an expanded and upgraded fleet of high-resolution mass spectrometers (HRMS), with the addition of three new TripleTOF HRMS systems for GLP quantitation, two in the Newark, Delaware facility and one in the Suzhou, China laboratory. As part of this expansion, QPS has hired Larry Mallis, Ph.D., Director of Bioanalysis, to lead the newly merged biotherapeutics and biomarkers Liquid ChromatographyMass Spectrometry (LC-MS) quantitation team in Delaware.

The QPS facility in Newark, Delaware, now has four high-resolution mass spectrometers: two 6600+, one 6600, and one 5600, all of which are being used for Good Laboratory Practice (GLP) quantitation and metabolite identification.

"QPS has been closely watching the trends in the market and we are committed to responding to the needs of our clients by dedicating four of the five TripleTOF Ultra-Performance Liquid ChromatographyHigh-Resolution Mass Spectrometry (UPLC-HRMS) systems to quantitation of oligonucleotides and intact proteins," said John Kolman, VP, Global Head of Translational Medicine, QPS LLC.

"This increase in capacity and capability comes at a pivotal moment for QPS in China, as we continue our two-decades-long global effort to support the pharma industry in developing antiviral therapeutics and/or vaccines. This has become a higher priority in view of the new public health concerns due to the novel coronavirus," said Yondong Zhu, VP, Head of Bioanalytical Services, QPS China.

Larry Mallis, Ph.D., leader of the newly formed team in Newark, Delaware, built his career in the pharmaceutical industry (BMS, Wyeth, and Merck), before moving into the CRO industry, most recently as Director of Bioanalytical Operations at Lovelace Biomedical Research Institute. This new group now has all the necessary LC-MS and other chromatographic technology for PK/PD bioanalysis to support clients in drug discovery and development of rare diseases. This group's expertise lies in the quantitation of oligonucleotides, peptides, intact proteins, and highly hydrophilic low-molecular-weight metabolite biomarkers by UPLC-HRMS, or by immunoaffinity UPLC-MS/MS (tandem mass spectrometry), or by hybridization-LC-fluorescence.

ABOUT QPS HOLDINGS, LLC

Since 1995, QPS has provided discovery, preclinical, and clinical drug development services. An award-winning leader focused on bioanalytics and clinical trials, QPS is known for proven quality standards, technical expertise, a flexible approach to research, client satisfaction, and turnkey laboratories and facilities. QPS has CLIA-certified and GLP-compliant laboratories ready to fast-track your novel coronavirus and COVID-19 RT-qPCR/QPCR and Serological Assays and vaccine development programs. For more information, visitwww.qps.comor email[emailprotected].

QPS CONTACT:

Name: Gabrielle Pastore Phone: 1-302-635-4290 Email: [emailprotected]

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SOURCE QPS

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QPS Continues to Expand UPLC-HRMS Quantitation Capabilities to Support Gene Therapy and Protein Drug Development - PRNewswire

Novartis wins conditional EU approval for gene therapy Zolgensma – Reuters

FILE PHOTO: The logo of Swiss drugmaker Novartis is pictured at the French company's headquarters in Rueil-Malmaison near Paris, France, April 22, 2020. REUTERS/Charles Platiau

ZURICH (Reuters) - Novartis won European approval for its gene therapy Zolgensma for the hereditary disease spinal muscular atrophy (SMA), the Swiss drugmaker said on Tuesday, adding it is in talks over price with countries in hopes of a quick launch.

The European Commission gave conditional approval to the therapy, whose U.S. price is $2.1 million, for patients with a clinical diagnosis of SMA Type 1, the most severe form of the disease, or SMA patients with up to three copies of a specific gene that helps doctors predict how severe the disease will be.

The EU approval covers babies and young children with SMA up to 21 kilograms. The medicine also has approval in Japan.

Novartis got Zolgensma with its $8.7 billion takeover of U.S.-based AveXis in 2018 and has forecast more than $1 billion in sales for the treatment, which in trials has been shown to significantly improve survival and motor function of babies with SMA, in particular those treated before symptoms develop.

Novartis said it is in talks with nations over what it calls its Day One access program, which the Basel-based drugmaker said is aimed at speeding up treatment by dealing with payment issues up front, even before national pricing and reimbursement agreements with individual countries are in place.

The Day One access program ensures the cost of patients treated before national pricing and reimbursement agreements are in place align with the value-based prices negotiated following clinical and economic assessments, Novartis said, adding the medicine will be immediately available in France.

Drug pricing in Europe varies from country to country, often relying on individual negotiations with regulators and pricing watchdogs that can slow down access, including in instances where officials conclude companies are seeking too much money for their medicines relative to the value they bring.

Reporting by John Miller; editing by Thomas Seythal and Brenna Hughes Neghaiwi

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Novartis wins conditional EU approval for gene therapy Zolgensma - Reuters

The Roller Coaster of Gene Therapy… – Labiotech.eu

By 2027, the global gene therapy market is estimated to reach a staggering value of $6.6B. With the number of successfully approved gene therapies increasing, the sector has moved from hype to hope. At the heart of gene therapy lie viral vectors, which are used to transport a gene into a target cell. Here we explore the current bottleneck in viral vector production, why viral vectors still outshine non-viral vector solutions, and what we can expect in the future.

The gene therapy field is gaining momentum. Investments are pouring in. The FDA is estimating that by 2025 it will approve between 10 and 20 cell and gene therapy products every year. This shows that a treatment, which started out as a hype, is now a real hope, says Ratish Krishnan, Associate Director of Cell and Gene Therapy Bioprocessing at MilliporeSigma*.

Today, a number of treatments have been approved, such as Spark Therapeutics LUXTURNA, the first FDA approved in vivo gene therapy, or Novartis Zolgensma, which gained US approval in 2019 and European approval in March 2020.

One of the key ingredients of gene therapies is the viral vector, which is used to transfer a gene of interest into a target cell. The most commonly used vector is that of the adeno-associated virus (AAV). But the manufacturing of viral vectors and scaling up their production remain difficult.

In upstream development, one challenge is the way viral vectors are produced. In a process called transient transfection, plasmids carrying the DNA of interest are introduced into host cells that will produce the viral vectors.

But host cells are commonly grown in adherent cell cultures, which are usually harder to reproduce at a large scale. So to scale-up and achieve high titers of virus particles, researchers are working on growing cells in suspension using large bioreactors instead.

We are facing several challenges at the moment and that is what keeps us on our toes, Krishnan adds. In upstream development, there is a desire to move towards suspension. Most processes use transient transfection methods using plasmids and the transfection step at a production scale of 500L or 2000L is extremely challenging.

In downstream development, researchers are studying the purity of capsids. The capsid is the protective shell of the virus enclosing the gene of interest. Related to this is an important discussion on the purity of viral vectors.

When you produce vectors, you will generally have a population of empty capsids, which is the viral AAV assembly without the genetic material inside, or partially-full capsids with only part of the DNA inside, Krishnan explains. We have to better understand the role of empty capsids inside the body. Are they needed as immune decoys or are they strictly considered impurities? In theory, you only need the ones with all the DNA inside, the full capsids.

But researchers have yet to discover the correct percentage of full capsids in a drug substance or product, Krishnan says. We dont have the answer yet. Typically, the strategy leans towards the enrichment of a percentage of full capsids as high as possible, while taking into account the data from clinical trials.

Questions about purity are difficult to answer because there is little or no regulatory guidance. For instance, compared to monoclonal antibodies (mAbs) for which the regulatory environment is well understood, the regulatory landscape for gene therapies remains largely unclear.

Through decades of research, mAb production also works through well-established and standardized platforms, whereas viral vectors are still in their infancy and cannot be produced using platform technologies yet although much is being done in this field and they are catching up fast.

Because of their longstanding history, we already have a lot of knowledge and research about mAbs, Krishnan explains. Lets say I want to start a biotech company or a CDMO that develops mAbs. I can rely on existing templates and get up and running much quicker than if I were developing viral vectors.

AAVs come in many different serotypes distinguishable strains which impact platform development. The scale-up is also challenging since the indications can be strikingly contrasting. For example, ocular indications need smaller viral drug substances compared to a muscular indication.

Manufacturing mAbs is better understood than manufacturing viral vectors. Viruses are a whole lot bigger and can be more complex than antibodies. While antibodies usually have a size around 10 nm, AAVs measure around 20nm and Lentiviruses around 100nm in size. Not only are antibodies produced at a larger scale than viral vectors, but their scalability is also more predictable due to the established platform technologies.

Despite these challenges, the increase in popularity, investments flooding in, and the promise of essential cures have led to a bottleneck in viral vector production for gene therapies. But many companies working in the gene therapy field are small or emerging biotechs that do not have the necessary resources and expertise in-house to tackle the challenges of viral vector production.

Lacking the facilities to do it themselves, small and emerging biotechs therefore turn to experienced contract development and manufacturing organizations (CDMOs), such as Merck BioReliance, to produce their gene therapies.

There are only a handful of CDMOs that have the capability and expertise to take on the complexities of gene therapy projects, Krishnan says. But there is currently a bottleneck in manufacturing slots. Manufacturing facilities can only work 24 hours a day, and if you are a small company and a CDMO has other clients waiting in line before you to have their therapies manufactured, you have no other option but to wait.

The problem with waiting, of course, is that the biotech runs the risk of falling behind its competition. Krishnan emphasizes, time is of the essence in gene therapy. There is no silver medal for developing a therapy for the same indication.

The key, says Krishnan, lies in much planning and close engagement with the CDMO partner. Biotechs should do an analysis of what they can perform in-house versus what they have to outsource early on. Engaging a CDMO is the route you want to take.

With decades of experience, Merck can support its biotech sponsors all the way to the clinic. We are big on the concept of integrated solutions, Krishnan explains. From clone to clinic to commercialization, Merck has the expertise, knowledge network, product, and services to help guide any customer to the finish line. We have the CDMO expertise with BioReliance, with testing services, gene therapy expertise, and regulatory support.

To circumvent the manufacturing bottleneck for viral vectors, some biotechs are looking at non-viral vector solutions for gene therapies. While traditional gene therapies use a viral vector, like AAV, to transfer a gene of interest into the patient, non-viral gene therapy deploys an alternative delivery system for the gene of interest.

Examples for non-viral delivery systems include physical force to deliver the gene through the cell membrane; injecting the gene with a needle into the target region; electroporation, which uses an electric current to produce pores in the cell membrane through which the gene can be inserted into the cell; and chemical vectors, such as lipid-, polymer-, or peptide-based particles.

Nevertheless, viral vectors, such as the AAV, remain the preferred path for most companies. The efficiency of delivery for non-viral vectors remains questionable. This means that there might be reactions in the immune system that get triggered, eliciting a dangerous, adverse response. AAVs, on the other hand, are well-engineered and safe, despite being novel.

Viral vectors have recently demonstrated success, Krishnan adds. Scientists are making advances in the non-viral area of gene therapy but they also come with a unique set of challenges. Questions, such as how do they interact with serum components in the body, how do they involve the immune system before reaching the target tissue, how do they interact with the surfaces of cells, remain.

Despite unaddressed challenges, gene therapy has definitely shifted from being a hope to carrying an expectation. This is reflected in the number of investments pouring into the sector.

Big pharma and biotech companies are heavily investing their resources into gene therapy, Krishnan says. Typically, companies have vaccines or mAbs in their portfolio. Now, gene therapy is becoming a major modality of interest as well.

While we are still far away from reaching the smooth manufacturing processes we have in place for antibodies, many companies are also looking into platform approaches for gene therapy. We would take a quantum leap if we developed a platform approach for upstream and downstream processes. That would significantly reduce the time to the clinic. Platform approaches are definitely being explored, Krishnan adds.

Vendors like Merck are playing a big role in developing fit-for-purpose products for gene therapies, Krishnan says. At the R&D level, researchers are also working on advances in capsid engineering. We already have synthetic capsids, and there are other tremendous advancements in capsid engineering, design, and purity, which are going to continue to evolve.

But, as Krishnan puts it, We are running a marathon at sprint speed. The journey is exciting and challenging, identical to the ride on a rollercoaster, but we are barely even at the tip of the iceberg. There are patients waiting for life-saving treatment, so gene therapies will definitely continue to be in the limelight, and for good reason.

Are you fighting to solve the bottleneck in viral vector production? Get in touch with the expert team at Merck and view their webinar on this topic!

*The life science business of Merck operates as MilliporeSigma in the U.S. and Canada.

Images via Shutterstock.com and Elena Resko

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The Roller Coaster of Gene Therapy... - Labiotech.eu


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