Commercial Insights

Cell & Gene Therapy Commercial Insight – October 2017

Mark Curtis & Richard Philipson

Providing a critical overview of the sector’s commercial developments – M&As, licensing agreements & collaborations, financial results, IPOs and clinical/regulatory updates, with commentary from our Expert Contributors.

CELL THERAPY:

Universal Cells inked two collaborations this month, with Astellas and BlueRock, that will see its gene editing technology put to use for the generation of therapeutics based on gene-edited induced pluripotent stem cells. The Astellas Institute for Regenerative Medicine (AIRM) and Universal Cells entered a global license agreement to research and commercialize a novel cell therapy technology. Under the terms of the agreement Astellas will fully fund the research work, and while Astellas will gain global rights to the technology following development, Universal Cells has an ability to earn up to $9M in upfront payments, $115M in clinical and regulatory milestones, and a royalty. So the deal has the potential to be fruitful for both parties.

GENE THERAPY:

This month’s news is dominated by Spark Therapeutics’ success at a recent FDA Advisory Committee, which gave its unanimous recommendation to approve the company’s treatment for RPE-65-mediated inherited retinal disease. Of course, a formal decision on Spark’s Biologics License Application is still awaited from FDA, but the chances of this being negative now seem vanishingly small. The pricing of the product will be interesting, as the treatable population is limited (1000 – 3000 patients in the USA), but the company has plenty of other products in the pipeline with the potential to bring it further growth. uniQure has also had success with regulatory authorities this month, with the award of Orphan Drug Designation for is Huntington’s disease treatment from FDA, and agreement from both FDA and EMA on its phase 3 plans using an improved transgene with higher factor IX protein expression for haemophilia B.

DOI: 10.18609/cgti.2017.077
Citation: Cell Gene Therapy Insights 2017; 3(9), 769-782.

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Expert Insight

Doggybone™ DNA: an advanced platform for AAV production

Spotlight Article

Short communication

Kinga Karbowniczek, Paul Rothwell, Jon Extance, Sarah Milsom, Vera Lukashchuk, Kevin Bowes, Daniel Smith & Lisa Caproni

STRATEGIES FOR SCALE-UP & SCALE-OUT

Recombinant adeno-associated virus (AAV) represents one of the most promising delivery vehicles for genetic medicines. However, the manufacture of plasmid DNA for the production of AAV presents a number of significant challenges, including scalability, fidelity, mis-incorporation of plasmid-derived DNA sequences, high costs and long lead times for GMP production. Touchlight has developed a novel, rapid, in vitro, enzymatic technology for multi-gram scale GMP manufacture of DNA that addresses all of the issues of DNA manufacture for AAV production. The process combines the use of two enzymes; Phi29 DNA polymerase and a protelomerase to generate covalently closed, linear DNA constructs known as doggybone™ DNA or dbDNA™. The process is rapid, cost effective, of high fidelity and eliminates antibiotic resistance genes. Here we present a case study, with data generated by Cobra Biologics as part of an on-going Innovate UK-funded collaboration, demonstrating that AAV particles can be produced using dbDNA™ with total and genomic titres equivalent to AAV particles made with plasmid DNA. In parallel experiments, with an academic collaborator, we have seen in vivo expression of reporter genes after administration of AAV vectors manufactured using dbDNA™ (unpublished data). As such, we believe that dbDNA™ has the potential to resolve a number of significant challenges in the production of AAV vectors at both clinical and commercial scale.

Submitted for review: Aug 29 2017 Published: Nov 16 2017
DOI: 10.18609/cgti.2017.074
Citation: Cell Gene Therapy Insights 2017; 3(9), 731–738.
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Obstacles for rAAV Clinical Trials: a question of vector supply and demand or know-how

Spotlight Article

Expert Insight

David J Dismuke & Robert M Kotin

STRATEGIES FOR SCALE-UP & SCALE-OUT

Recent, positive, gene therapy clinical studies, using recombinant adeno-associated virus (rAAV) vectors, indicate the potential of this therapeutic platform for treating monogenic and acquired diseases. Although these studies are auspicious, realizing the full potential of rAAV gene therapy will require improved access to economical and scalable sources of vector. The complexities of the virus vector system and the limitations of transient production platforms have driven up cost-of-goods and extended the turn-around time for process development and manufacturing of clinical grade rAAV. This manufacturing bottleneck is likely to worsen due to the recent growth of the field, putting pressure on companies to address their clinical production strategies. The production platforms currently in use for clinical rAAV are discussed and we propose that direct experience is critically important for vector production campaigns to succeed in a timely manner.

Submitted for review: Oct 10 2017 Published: Nov 16 2017
DOI: 10.18609/cgti.2017.075
Citation: Cell Gene Therapy Insights 2017; 3(9), 755-768.
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Scale-up of lentiviral vectors for gene therapy: advances and challenges

Spotlight Article

Expert Insight

Alexandra McCarron, Martin Donnelley & David Parsons

STRATEGIES FOR SCALE-UP & SCALE-OUT

Growing interest in the use of lentiviral (LV) vectors for gene therapy applications has resulted in demand for production processes that are amenable to large scale. However, up-scaling LV manufacturing poses a number of challenges for process developers and regulatory bodies, which need to be overcome in order to cost effectively generate a gene therapy product in large quantities. Recently there has been progress in developing workflows capable of producing and processing LV vector at sufficient levels for human gene therapy applications. Accordingly, this article will cover the current state of LV upstream and downstream processing, ongoing challenges of up-scaling manufacturing, recent advances and improvements, and future perspectives.

Submitted for review: Sep 15 2017 Published: Nov 16 2017
DOI: 10.18609/cgti.2017.072
Citation: Cell Gene Therapy Insights 2017; 3(9), 719-729.
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Importance of Innovation and Design in the Scalability of Cell & Gene Therapies

Spotlight Article

Interview

Stephen Ward, Julie Kerby, Damian Marshall

Strategies for Scale-up & Scale-out

Stephen-Ward-headshot-100x120Julie-Kerby-Headshot-120x100Damian-Marshall-Headshot-120x100

 

STEPHEN WARD: Stephen was appointed Chief Operating Officer of the Cell Therapy Catapult in January 2013. He brings over 20 years of biological medicine research, development, and manufacturing experience to the organisation. Stephen enjoys bringing cutting edge technologies to patients, by developing commercially viable products and has developed and validated scaleable, commercial manufacturing processes for cell based medicinal products, vaccines, and recombinant biologicals. Prior to joining the Cell Therapy Catapult, Stephen worked for a number of biotech and biopharma companies at Board level. Stephen was Development Director at both Onyvax and Stabilitech. At Stabilitech he led the exploitation of the company’s vaccine and biopharmaceutical stabilisation platform, and expanded it into the cell therapy arena. At Onyvax he played a key executive role in the Immune oncology programme, and at Medeva he worked on the hepatitis immunotherapy and antigen delivery platform. Stephen is passionate about securing and growing the cell and gene therapy manufacturing and development supply chain. He is the current Chair of the BIA’s Manufacturing Advisory Committee, actively promoting and supporting UK bio-manufacturing at Government as well as grass root level. He, also, sits on various academic Advisory Boards. His first degree was from the University of Birmingham, specialising in Infection and Immunity, and his second degree from the Medical School of Southampton University developing group B meningococcal vaccine candidates.

JULIE KERBY: Working closely with our collaborators she is responsible for the development and technical transfer of cell and gene therapy manufacturing processes ensuring they meet quality and regulatory requirements. Julie has more than 20 years’ experience across large pharma, biotech and academic laboratories, including 7 years at Pfizer Ltd as Biology Lead for a cell replacement therapy for Age Related Macular Degeneration which achieved First-in-Human in 2015. Julie holds a BSc. Hons degree in Biology from the University of Southampton.

DAMIAN MARSHALL: Joining the Cell and Gene Therapy Catapult in August 2013, Damian leads the assay development and validation team which underpins a diverse portfolio of cell therapy products at various stages of clinical maturity from pre-FiM to phase III. Damian has over 15 years of assay development experience in the cell therapy and life sciences fields having previously managed the R&D portfolios for both SMEs and LGC Ltd and has successfully managed a European life sciences business with an annual turnover in excess of £15million. Damian graduated with a degree in biological sciences and a PhD in developmental biology from Manchester University.

DOI: 10.18609/cgti.2017.078
Citation: Cell Gene Therapy Insights 2017; 3(9), 783-792.
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Scale-up of platelet production from human pluripotent stem cells for developing targeted therapies: advances & challenges

Spotlight Article

Expert Insight

Jonathan N Thon & Sven M Karlsson

STRATEGIES FOR SCALE-UP & SCALE-OUT

Without question, the future of regenerative medicine is in the scalable production of transfusable human tissues for therapeutic use. Platelets will be among the first of these stem-cell based therapeutic tissues to be developed and adopted for clinical use, most notably because they are anucleate and can be safely irradiated to substantially reduce the risk of teratoma development and other cell contaminants. Furthermore, platelets are short-lived, well characterized, easily transplanted, are not required to be autologous, and support a larger than $20 billion per year global market that relies entirely on human volunteer donors. While we are within a decade of realizing the potential of stem cell-based therapeutics, this was not obvious only several years ago. This article identifies the major logistical challenges associated with commercially scaling platelet production for therapeutic use and our experiential insights into translating this technology to the clinic.

Submitted for review: Sep 6 2017 Published: Nov 16 2017
DOI: 10.18609/cgti.2017.068
Citation: Cell Gene Therapy Insights 2017; 3(9), 701-718.
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Approaches and challenges for the manufacture and scale-out of autologous cell therapies

Spotlight Article

Interview

Richard P Harrison

Strategies for Scale-up & Scale-out

 

Dr Richard Harrison is an EPSRC ETERM Fellow at Loughborough University. His research is primarily focused on the manufacturing of advanced therapies, more specifically the future manufacturing paradigms these advanced therapies will require. As these advanced healthcare products do not fit easily into existing manufacturing solutions, Richard’s research examines the business models, distribution networks, cost of goods and reimbursement strategies that may suit these therapies, and cost of goods modeling. A particular focus of this strategy is investigating the feasibility of decentralized manufacturing of advanced therapies across diverse geographical regions. Richard holds a BSc in Biochemistry, an MSc in Stem Cell Technologies and a PhD in targeting of cell therapies. He was awarded his E-TERM Landscape Fellowship in 2016 and is currently based at Loughborough University with Visiting Fellow status at The University of Nottingham.

DOI: 10.18609/cgti.2017.076
Citation: Cell Gene Therapy Insights 2017; 3(9), 749-753.
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