Gene therapies are some of the hottest areas of investment in the biotech world, as are artificial-intelligence-assisted research methodologies, and Dynos right there at the intersection of these two things, Dyno CEO Eric Kelsic said.

Potential partners have been trying to get in on the action since the company's founding two years ago. Now, Cambridge, Massachusetts-based Dyno unveils its third partnership in the last five months: a pact with Roche and its Spark Therapeutics unit to develop central nervous system (CNS) and liver-directed gene therapies.

All told, the deal could exceed $1.8 billion in clinical and sales milestones, but the companies kept mum on how much Dyno's getting in an upfront fee and research funding.

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A big challenge with gene therapies is ensuring the payloads are delivered effectively and safely via their delivery vehicles. Traditionally, adeno-associated virus(AAV) vectors have limitations because they are difficult to manufacture, can only carry a limited payload and can only target certain tissue types. What's more, gene therapies delivered by AAV may not work in people who have developed a natural immunity to this type of virus.

The second challenge lies in the creation of new capsids, or the protein shell that coats viral vectors and targets cells.

There's this analogy of the protein universe. And capsids are like stars in the galaxy; most of the space is empty. We would like to find the most interesting areas to have the best capsids for in vivo gene therapy, but the space is so large that it can't search it all, Kelsic said.

Thats where Dynos AI-powered approach comes in. We do experiments to gather information about that space, then using machine learning, we build an app, and using those machine learning models, we navigate to the most interesting areas of that space, say the galaxies or the certain solar systems, which have the most interesting stars for gene therapy, he said.

RELATED: Novartis, Sarepta tap Dyno to unearth new gene therapy vectors

The partnership will play to each organizations strengths, Kelsic said, with Dyno focusing on designing, developing, testing and validating capsids using AI, and Roche and Spark adding their own payloads, advancing development and commercializing the gene therapies.

Now, with its third partnership under its belt, Dyno is working in the four areas where theres the most activity in gene therapy according to Kelsic: CNS and liver disorders with Roche, eye disorders with Novartis and muscle disorders with Sarepta Therapeutics.

As for whats next for Dyno, the company has already started the work of designing experiments for both the CNS and liver and is continuing to build its team, which has already grown from 20 to 40 employees over the last five months in what Kelsic calls a hyper-growth trajectory.

We've been making significant progress both in terms of building the team and building the platform, he said, but also building up these technologies, these tools, and applying them against a really challenging, but important problem.

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Dyno, Roche to tackle CNS, liver disease in gene therapy deal worth up to $1.8B - FierceBiotech

While the US Food and Drug Administration (FDA) is still receiving investigational new drug applications (INDs) for cell and gene therapies, officials are concerned about the impact of the COVID-19 pandemic on clinical trials.Its clear that COVID-19 has adversely affected all aspects of development of cell and gene therapies, said Peter Marks, director of FDAs Center for Biologics Evaluation and Research (CBER), said at the Alliance for Regenerative Medicines Meeting on the Mesa. For some of the studies that are ongoing there are some real challenges to overcome in terms of endpoints that may have been missed.The pandemic also has disrupted global harmonization efforts around gene therapies, Marks said.We were on the cusp, in fact, working with global regulators trying to get towards more harmonization of gene therapy programs in different countries, he said. Were trying to keep it moving but its a challenge to do.Marks noted that before COVID-19 he spent about 75% of his time on cell and gene therapies, but the pandemic has forced him to shift priorities. Some things have less policy demands at this point in time. At this point in time its very much reversed and its probably 80% of my time on COVID-related activities.Marks also noted that CBERs Office of Tissues and Advanced Therapies (OTAT) has been struggling to keep up with its workload even before the pandemic. With the influx of applications for cell and gene therapies over the last five years, Marks said the office, Should have doubled in size and its only modestly larger, 15-20% larger in size.Marks said he is not satisfied with the level of dialogue the agency has been able to have with gene therapy developers. Especially early on, we should be able to have this dialogue that really facilitates setting things up well so that our knowledge of the entire fieldwe help leverage that for every sponsor.Weve been so strapped in terms of personnel that its hard to do that, Marks said, noting that COVID-19 has exacerbated things even further. Because the number of gene therapy applications hasnt fallen off dramatically, some of the trials may not be moving as quickly, but the applications keep coming in. Marks said that OTAT has also had to shift priorities during the pandemic and that he hopes the next user fee cycle will bring in the resources necessary to staff up further.Speaking on a separate panel with members of industry, OTAT Director Wilson Bryan echoed Marks sentiment.We were stretched thin before the pandemic, and with the flood of work that came in, it really had an impact, he said. Sometimes folks dont like to admit this, but we all know weve had delayed meetings, weve had to delay review of some applications because of giving priority to the pandemic.However, Bryan said the office is getting its balance and is working to catch up on some of its delayed activities.Bryan expressed some worry about the financial well-being of some of the smaller companies his office works with. Were hearing a lot about their struggles to stay afloat and continue and finish off their development programs and whether or not those development programs are going to be sufficient to meet regulatory standards, he said.One of the challenges, said Timothy Schroeder, CEO of CTI Clinical Trial & Consulting, will be dealing with gaps in data from clinical trials. The question is going to be how do sponsors, how do regulatory authorities and how do companies such as ourselves fill those gaps?On the regulator side, Bryan said his office is working with companies on an individual basis to sort out those issues, which differ from one indication to the next.Bryan added that one positive to come of the pandemic is greater interest in remote outcome assessments in clinical trials. If we have an energy now to develop outcome measures and validate outcome measures that allow us to reliably capture information from patients in remote locations, that will ultimately facilitate development, he said.The pandemic also has significantly disrupted FDAs ability to conduct surveillance and preapproval inspections. While the agency has resumed some domestic inspections and mission-critical foreign inspections, it also is leveraging other sources of information, including inspection reports from other regulators, and requesting documents from applicants and facilities in lieu of on-site inspections where possible. (RELATED: FDA issues pandemic inspections FAQ guidance, Regulatory Focus 19 August 2020).Were considering virtual inspections, particularly for companies where the site has a track record, but if its a site that is brand new with no track record or if its a site with that has a bad track record, were hesitant to do that, Bryan said.Bryan also raised the prospect of FDA inspectors tagging along remotely for an inspection being conducted by other regulators. Is it possible that we could have an inspection by European inspectors and have US regulators going along for a virtual inspection at the same time? We think about those things, I dont know that weve done them yet, Bryan said, adding that he is not sure whether FDA inspectors would be comfortable with the information they would get.Curran Simpson, chief operations and technology officer at REGENXBIO, said he sees promise in virtual audits and believes the level of documentation a site provides can be indicative of its compliance.How often have I walked into a manufacturing facility thats well-run but has terrible documentation? Almost never. I think virtual audits, if you do a risk-based approach and the audit partner has the ability to send documentation in an efficient way and you have experienced people doing this, I think youre going to get the same flavor of an audit very quickly from the level of the documentation, he said.Of course, youll want to accompany that to the extent possible with imaging of the facility, Curran said, To see if those practices are being followed, the overall cleanliness of the facility and the management of material movement If you dont get a good impression from the documentation that youre working through, its probably a bigger issue that you want to escalate.Amy DuRoss, co-founder and CEO of Vineti, an enterprise software company specializing in advanced therapies, expressed some doubts about the current potential for fully remote audits.Certainly our piece of the chain because were enterprise software is readily auditable remotely, but I would say that the overall system and in manufacturing, Im not sure weve evolved as a species yet to adapt our remote techniques to get a full picture I dont think were there yet, she said.

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FDA officials, experts discuss impact of COVID-19 on cell and gene therapies - Regulatory Focus

Roche has signed a collaborative agreement with Dyno Therapeutics for the development of adeno-associated virus (AAV) vectors for gene therapies for central nervous system (CNS) disease and liver-directed therapies.

Under the terms of the agreement, Dyno will design novel AAV capsids with improved functional properties for gene therapies, while Roche and its subsidiary Spark Therapeutics will be responsible for preclinical, clinical and commercialisation activities for gene therapy product candidates using the novel capsids.

Roche will pay Dyno an undisclosed upfront payment, as well as additional payments during the research phase of the collaboration.

In addition, Dyno is eligible to receive clinical and sales milestone payments and royalties for any resulting products, with all of these payments potentially exceeding $1.8bn.

Dynos CapsidMap platform is used to identify novel AAV capsids the cell-targeting protein shell of viral vectors optimising tissue targeting and immune-evading properties, in addition to improving packaging capacity and manufacturability.

We strongly believe in the potential of gene therapy and are excited to bring together experts from Roche, Spark and Dyno to develop next-generation gene therapies, said James Sabry, head of Roche Pharma Partnering.

Dynos innovative AI-powered approach to designing optimized AAV vectors will further complement and build on our progress in gene therapy. We look forward to leveraging Dynos technology to develop new, innovative treatments for patients across CNS and liver-directed therapies, he added.

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Roche signs deal with Dyno Therapeutics for gene therapy vectors - PharmaTimes

The drug discovery pipeline can take, on average, a decade to get from the lab to the patient. Ori Biotech aims to speed up the innovation of cell and gene therapies via the manufacturing platform it is bringing to market.

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The London and Woodcliff Lake, New Jersey-based company is developing a platform that closes, automates and standardizes manufacturing for cell and gene therapy developers so they can move their treatments from the pre-clinical process through to scale commercially.

These products are super expensive to manufacture, and even with the biggest good manufacturing practices in place, you couldnt do beyond a few thousand doses, Farlan Veraitch, Ph.D., co-founder and chief scientific officer at Ori Biotech, told Crunchbase News. We are using our novel automation to reduce the cost of goods and the footprint. Producing hundreds of thousands of doses per year is impossible right now, but with Ori you will be able to do it.

Helping the company get its platform on the market is a new $30 million Series A round of funding led by Northpond Ventures, with participation from Octopus Ventures and Oris existing institutional investors: Amadeus Capital Partners, Delin Ventures and Kindred Capital. The new funding gives Ori Biotech a total of $40 million in funding since its inception in 2015, including a $10 million seed round in 2018, Veraitch said.

In addition to taking the platform to the market, estimated to be in late 2021 or early 2022, the company expects to double its employee count in the next four months and double that again by next year. Currently, the company has eight employees, including its first two in the U.S.

The company has been working with external partners over the past four months doing testing. One partner is already getting good results from testing the platform on its treatment for solid tumors, Ori Biotechs CEO Jason Foster said in an interview.

We are hoping to grow our external partnerships from three to six in the next year, Foster added.

Meanwhile, the company is addressing a $9 billion market that has 1,500 gene therapy clinical trials going on in cancer, diabetes and rare diseases. There are approximately eight approved products, and most are in pre-clinical or Phase 1 testing, he said.

Sharon Kedar, co-founder and partner at Northpond Ventures, said in an interview that Veraitch is obsessed with how cell and gene therapies need to be brought to market.

Northpond looked at a lot of companies in this space, and thought the Ori Biotech team and modular approach was differentiated and had the opportunity to change how these therapies are made.

Farlan and Jason are phenomenal humans doing critical work, she said. Globally speaking, the health care system is broken, and the cost of developing drugs is outpacing the ability to pay for them. Now you can treat someone on a personalized basis without the cost burden, and Ori has a chance to be that solution.

Illustration: Li-Anne Dias

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Exclusive: Ori Biotech To Use $30M Series A On Cell, Gene Therapy Manufacturing Platform - Crunchbase News

DetailsCategory: DNA RNA and CellsPublished on Friday, 16 October 2020 13:44Hits: 238

- Study targets a chronic autoimmune skin disorder affecting approximately 50,000 patients in the U.S. -

EXTON, PA, USA I October 15, 2020 I Castle Creek Biosciences,Inc, a privately-held, clinical-stage cell and gene therapy company leveraging its proprietary fibroblast technology platform to develop and commercialize innovative personalized therapies for underserved disorders with high unmet medical needs,announced that the first adult patient has been dosed in a Phase 1/2 clinical trial evaluating FCX-013, the company's investigational gene therapy, for the treatment of moderate to severe localized scleroderma.

"Dosing the first patient is an important milestone in the clinical development program for FCX-013, which we believe has the potential to be the first therapy to treat excessive collagen deposition at the site of localized scleroderma lesions in the skin and soft tissue," said John Maslowski, Chief Executive Officer of Castle Creek Biosciences. "Our hope is to relieve the debilitating, painful impact of localized scleroderma in patients who currently have limited treatment options."

Localized scleroderma is a chronic autoimmune skin disorder that leads to the excess production of collagen and causes thickening of the skin and connective tissue. In moderate to severe forms of the disorder, patients can experience discomfort, tightness and pain that limits their ability to function. Approximately 50,000 patients in the U.S. have moderate to severe localized scleroderma. Current treatment options include systemic or topical corticosteroids that target inflammation, UVA light therapy, and physical therapy. There are no U.S. Food and Drug Administration (FDA) approved therapies for patients living with this disorder.

"Localized scleroderma may be characterized based on the depth and pattern of lesions, and there are currently few treatment options to address the excessive collagen accumulation in the skin and connective tissue," said Mary Spellman, M.D., Chief Medical Officer of Castle Creek Biosciences. "With our proprietary fibroblast technology, we have an opportunity to develop and evaluate new personalized therapies that are designed for durability and formulated to be compatible with each patient's unique biology."

The open label, single cohort Phase 1/2 clinical trial is evaluating the safety of FCX-013 as its primary objective. Secondary objectives include assessments of fibrosis at targeted sclerotic lesions at various time points through 26 weeks post-administration of FCX-013.The trial will enroll up to 10 patients with moderate to severe localized scleroderma. More information about the Phase 1/2 trial is available at ClinicalTrials.gov and searching the identifier NCT03740724.

Castle Creek Biosciences is manufacturing FCX-013 at its in-house, current good manufacturing practices (cGMP), commercial-scale facility located in Exton, Pennsylvania.

About FCX-013

FCX-013 is Castle Creek Biosciences' investigational gene therapy candidate for the treatment of moderate to severe localized scleroderma. FCX-013 is an autologous fibroblast genetically modified using lentivirus and encoded for matrix metalloproteinase 1 (MMP-1), a protein responsible for breaking down collagen. FCX-013 incorporates a biologic switch activated by an orally administered compound to control protein expression at the site of the localized scleroderma lesions. FCX013 is designed to be injected intradermally at the location of the fibrotic lesions where the genetically-modified fibroblast cells will produce MMP-1 to break down excess collagen accumulation. FCX-013 has been granted Orphan Drug, Rare Pediatric Disease and Fast Track designations by the FDA.

About Castle Creek Biosciences

Castle Creek Biosciences, Inc. is a privately-held, clinical-stage cell and gene therapy company advancing innovative personalized therapies for underserved disorders with high unmet medical needs. The company is using its proprietary fibroblast technology platform to develop D-Fi (debcoemagene autoficel, formerly designated FCX-007), an investigational gene therapy for the localized treatment of wounds in dystrophic epidermolysis bullosa (DEB). The company is also developing FCX-013, an investigational gene therapy for the treatment of moderate to severe localized scleroderma. The company operates an in-house, current good manufacturing practices (cGMP), commercial-scale facility located in Exton, Pennsylvania. Castle Creek Biosciences is a portfolio company of Paragon Biosciences. For more information, visit castlecreekbio.comor follow Castle Creek on Twitter @CastleCreekBio.

About Paragon Biosciences

Paragon is a life science innovator that creates, invests in and builds life science companies in artificial intelligence, cell and gene therapy, synthetic biology and biopharmaceuticals. The company's current portfolio includes Castle Creek Biosciences, Emalex Biosciences, Evozyne, Harmony Biosciences, Qlarity Imaging, Skyline Biosciences, and a consistent flow of incubating companies created and supported by the replicable Paragon Innovation Capital model. Paragon stands at the intersection of human need, life science, and company creation. For more information, please visit https://paragonbiosci.com/.

SOURCE: Castle Creek Biosciences

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Castle Creek Biosciences Announces First Patient Dosed in Phase 1/2 Clinical Trial of FCX-013 Gene Therapy for Treatment of Moderate to Severe...