Trend Chart ON
INNOVATIVE BIOindustries

contents

November 2019, 7th
*FEATURE STORY* ● The Alliance for Regenerative Medicine outlines recommendations for increasing the number of European-based ATMP clinical trials *GENE THERAPY* ● Long-term correction of copper metabolism in WD mice with AAV8 vector delivering truncated ATP7b ● Enhancing the therapeutic potentiel of sulfamidase for the treatment of MPSIIIA *DISRUPTIVE TECHNOLOGIES* ● Immunotherapy in HER2-positive breast cancer: state of the art and future perspectives. CLINICAL TRIALS - DATA ● FDA orders Novartis to hit the brakes on a Zolgensma® trial after animal study spurs safety concerns ● Arrowhead Pharmaceuticals presents preclinical data on ARO-ENaC at the North American Cystic Fibrosis Conference *M&A - AGREEMENTS* ● Cognate BioServices announces acquisition of Cobra BiologiCs ● Dicerna enters agreement with Roche to develop and commercialize DCR-HBVS ● Roivant, Sumitomo alliance to target cystic fibrosis gene therapy ● Vineti and WuXi AppTec Advanced Therapies collaborate to simplify manufacturing supply chain for advanced therapies

November 2019, 7th

FEATURE STORY

● The Alliance for Regenerative Medicine outlines recommendations for increasing the number of European-based ATMP clinical trials

GENE THERAPY

● Long-term correction of copper metabolism in WD mice with AAV8 vector delivering truncated ATP7b

● Enhancing the therapeutic potentiel of sulfamidase for the treatment of MPSIIIA

DISRUPTIVE TECHNOLOGIES

● Immunotherapy in HER2-positive breast cancer: state of the art and future perspectives.

CLINICAL TRIALS - DATA

● FDA orders Novartis to hit the brakes on a Zolgensma® trial after animal study spurs safety concerns

● Arrowhead Pharmaceuticals presents preclinical data on ARO-ENaC at the North American Cystic Fibrosis Conference

M&A - AGREEMENTS
● Cognate BioServices announces acquisition of Cobra BiologiCs
● Dicerna enters agreement with Roche to develop and commercialize DCR-HBVS
● Roivant, Sumitomo alliance to target cystic fibrosis gene therapy
● Vineti and WuXi AppTec Advanced Therapies collaborate to simplify manufacturing supply chain for advanced therapies

FEATURE STORY

The Alliance for Regenerative Medicine outlines recommendations to increase the number of European-based ATMP clinical trials

The Alliance for Regenerative Medicine (ARM), the international advocacy organization representing the cell and gene therapy and broader advanced therapies sector, published on October 31st a report outlining the latest trends in clinical trials with advanced therapy medicinal products (ATMPs) based in Europe, and its recommendations to improve its competitiveness compared to other global regions. The report is based on a comprehensive global analysis of all new clinical trials with cell and gene medicinal products initiated between January 2014 to June 2019 and via an online survey with ARM therapeutic developer member organizations. It provides detailed insights on clinical trials, including the number, type of technology, development stage or approval process, specifically within Europe and also compared with other regions in the world . For further information, see the full report.

Should you wish any further accurate and reliable informations on these topics...
Please have a look at our latest report « Landscape in…. Gene Therapy Companies ».
Do not hesitate to download the sample pages or feel free to contact us olivier@octopusyx.fr or alb@biopharmanalyses.fr

Related Informations/Publications

-Drug Discov Today. 2019 Oct 16. pii: S1359-6446(19)30386-1. Horses for courses: an approach to the qualification of clinical trial sites and investigators in ATMPs. Hildebrandt M. TUMCells Interdisciplinary Center for Cellular Therapies, TUM School of Medicine, Munich, Germany. Link: Abstract
-Front Pharmacol. 2019 Aug 30;10:921. Regulatory Framework for Advanced Therapy Medicinal Products in Europe and United States. Iglesias-López C et al. Universitat Autònoma de Barcelona, Barcelona, Spain
Link: Abstract - Full Text

GENE THERAPY

Long-term correction of copper metabolism in WD mice with AAV8 vector delivering truncated ATP7b

Wilson's disease is an autosomal recessive disorder of copper metabolism caused by mutations in the ATP7B gene encoding a liver active copper transport enzyme. Gene therapy with adeno-associated virus (AAV) carrying full length ATP7b, which is about 4.4 kb, was shown to rescue copper metabolism disorder in WD mouse model. However, due to its relatively large size, the AAV vector containing full length ATP7b could be oversized for its packaging capacity, which could lead to inefficient packaging. For this purpose, researchers have engineered a truncated ATP7b mutant (tATP7b) that is about 3.3kb in length and used for AAV gene therapy for WD mice. In vitro test showed that the excretion of copper outside the cells could be achieved with tATP7b as efficient as the full-length ATP7b. In vivo delivery of tATP7b to WD mice by AAV8 vectors corrected their copper metabolisms and significantly rescued copper accumulation related syndromes, including reduced urinary copper excretion, increased serum ceruloplasmin and improved liver damages.
The results appeared in October 31st online issue of Hum Gene Ther .

Related Informations / Publications

-Hepatology. 2019 Jul;70(1):108-126. Liver Expression of a MiniATP7B Gene Results in Long-Term Restoration of Copper Homeostasis in a Wilson Disease Model in Mice. Murillo O et al. University of Navarra, Navarra Institute for Health Research (IdisNA), Pamplona, Spain
Results/Comments: Gene therapy using an optimized therapeutic cassette in different AAV systems provides long-term correction of copper metabolism regardless of sex or stage of disease in a clinically relevant WD mouse model
Link: Abstract
-Hum Gene Ther Clin Dev. 2019 Mar;30(1):29-39. A Gene Therapy Approach to Improve Copper Metabolism and Prevent Liver Damage in a Mouse Model of Wilson Disease. Greig JA et al. University of Pennsylvania, Philadelphia, Pennsylvania, USA Results/Comments: Researchers conclude that administering gene therapy at the early stages of disease onset is a promising approach for reducing liver damage and correcting copper metabolism in WD
Link: Abstract
-MAR 2019: Pfizer and Vivet to collaborate on development of potential breakthrough therapy for Wilson disease Results/Comments: Pfizer has acquired a 15% equity interest in Vivet and secured an exclusive option to acquire all outstanding shares
Link: Press Release

Enhancing the therapeutic potentiel of sulfamidase for the treatment of MPSIIIA

Mucopolysaccharidosis type IIIA (MPS-IIIA) is a lysosomal storage disorder (LSD) caused by inherited defect of sulfamidase, a lysosomal sulfatase. MPS-IIIA is one of the most common and severe forms of LSDs with central nervous system involvement. Presently there is no known cure. Researchers have developed a new gene delivery approach for the treatment of MPS-IIIA based on the use of a modified version of sulfamidase expression cassette. This cassette encodes both a chimeric sulfamidase containing an alternative signal peptide to improve enzyme secretion and SUMF1 to increase sulfamidase post-translational activation rate. They demonstrate that improved secretion and increased activation of sulfamidase act synergistically to enhance enzyme bio-distribution in wild type pigs upon intrathecal AAV9-mediated gene delivery. Translating such gene delivery strategy to a mouse model of MPS-IIIA results in a rescue of brain pathology, including memory deficits, as well as improvement in somatic tissues. These data may pave the way for developing effective gene delivery replacement protocols for the treatment of MPS-IIIA patients. The results appeared in October 29th online issue of Mol Ther Meth Clin Dev.

Related Informations / Publicationss

-Hum Gene Ther. 2019 Oct;30(10):1211-1221. In Vivo Gene Therapy for Mucopolysaccharidosis Type III (Sanfilippo Syndrome): A New Treatment Horizon. Marcó S et al. Universitat Autònoma de Barcelona (UAB), Bellaterra, Spain
Results/Comments: Ongoing clinical studies should shed light on which gene transfer strategy leads to highest clinical benefits while minimizing risks. The development of all these strategies opens a new horizon for treatment of not only MPSIII and other LSDs but also of a wide range of neurological diseases
Link: Abstract
-Mol Genet Metab Rep. 2019 Sep 7;21:100510. Intravenous delivery of a chemically modified sulfamidase efficiently reduces heparan sulfate storage and brain pathology in mucopolysaccharidosis IIIA mice. Gustavsson S et al. Research & Translational Science Unit, Swedish Orphan Biovitrum AB (publ), Stockholm, Sweden
Link: Abstract - Full Text
- JUL 2019: Abeona Therapeutics Announces Positive Interim Data from the ABO-102 Phase 1/2 Gene Therapy Clinical Trial in MPS IIIA
Link: Press Release

disruptive technologies

Immunotherapy in HER2-positive breast cancer: state of the art and future perspectives.

Breast cancer (BC) is a complex disease with primary or acquired incurability characteristics in a significant part of patients. Immunotherapeutical agents represent an emerging option for breast cancer treatment, including the human epidermal growth factor 2 positive (HER2+) subtype. The immune system holds the ability to spontaneously implement a defensive response against HER2+ BC cells through complex mechanisms which can be exploited to modulate this response for obtaining a clinical benefit. Initial immune system modulating strategies consisted mostly in vaccine therapies, which are still being investigated and improved. However, the entrance of trastuzumab into the scenery of HER2+ BC treatment was the real game changing event, which embodied a dominant immune-mediated mechanism. More recently, the advent of the immune checkpoint inhibitors has caused a new paradigm shift for immuno-oncology, with promising initial results also for HER2+ BC. Breast cancer has been traditionally considered poorly immunogenic, being characterized by relatively low tumor mutation burden (TMB). Nevertheless, recent evidence has revealed high tumor infiltrating lymphocytes (TILs) and programmed cell death-ligand 1 (PD-L1) expression in a considerable proportion of HER2+ BC patients. This may translate into a higher potential to elicit anti-cancer response and, therefore, wider possibilities for the use and implementation of immunotherapy in this subset of BC patients. The review appeared in October 29th online issue of J Hematol Oncol.

Related Informations / Publications

-Expert Rev Anticancer Ther. 2019 Sep;19(9):811-822. What therapies are on the horizon for HER2 positive breast cancer? Viale G et al. European Institute of Oncology IRCCS , Milan , Italy
Results/Comments: Identification of valuable predictive biomarkers is needed to better inform choice of treatment sequence for the individual patient and limit the financial toxicity of these agents. Link: Abstract
-Cancer Treat Res. 2019;178:45-80. Update on Precision Medicine in Breast Cancer. Sachdev JC et al. HonorHealth Research Institute, Scottsdale, AZ, USA Results/Comments: In this review, researchers outline the recent advances in technology and targeted treatments for breast cancer, the remaining challenges and ongoing efforts to address these to make precision medicine a reality for all breast cancer patients.
Link: Abstract

CLINICAL TRIALS - DATAS

FDA orders Novartis to hit the brakes on a Zolgensma® trial after animal study spurs safety concerns

Novartis announced on October 30th that the FDA placed a partial hold on clinical trials for intrathecal administration of AVXS-101.The announcement follows an Avexis communication to health authorities and clinical trial investigators based on findings from a small, Avexis-initiated pre-clinical study in which animal findings showed dorsal root ganglia (DRG) mononuclear cell inflammation, sometimes accompanied by neuronal cell body degeneration or loss. This partial hold by the FDA does not impact marketed Zolgensma® or AVXS-101 intravenous clinical trials. AveXis is studying AVXS-101 intrathecal administration in patients with spinal muscular atrophy (SMA) Type 2. The partial hold impacts enrollment in the high dose cohort of the STRONG trial, an ongoing, open-label, dose-comparison, multi-center trial designed to evaluate the efficacy, safety and tolerability of one-time intrathecal administration of AVXS-101. The low and mid dose cohort enrollment has previously been completed and interim results have been presented. The clinical significance of the DRG inflammation observed in this pre-clinical animal study is not known and was not seen in prior animal studies with AVXS-101. DRG inflammation can be associated with sensory effects. For further information, see MarketScreener

AveXis is one of the 230 companies deeply scrutinized in
our latest report "Landscape in...Gene Therapy Companies"

Do not hesitate to click here to get sample pages

Related Informations / Publications

- OCT 2019: Novartis' Zolgensma® faces EU, Japan delays after regulators raise 'manufacturing questions'
Link: FiercePharma
-AUG 2019: Novartis stands behind Zolgensma® (onasemnogene abeparvovec-xioi) for the treatment of children less than 2 years of age with spinal muscular atrophy
Link: Press Release
- AUG 2019 : Novartis says it knew of Zolgensma® data problems before U.S. approval Link: Reuters
- AUG 2019 : FDA Addresses Zolgensma® Gene Therapy Data Manipulation
Link: NeurologyLive

Arrowhead Pharmaceuticals presents preclinical data on ARO-ENaC at the North American Cystic Fibrosis Conference

Arrowhead Pharmaceuticals presented on October 31st preclinical data at the 2019 North American Cystic Fibrosis Conference (NACFC) on ARO-ENaC, an inhaled RNAi therapeutic being developed as a potential treatment for cystic fibrosis (CF), which is a rare disease caused by genetic mutations that lead to mucus buildup in the lungs and pancreas. Arrowhead is currently conducting IND/CTA-enabling studies to support regulatory filings in the first half of 2020 for first-in-human studies. ARO-ENaC is designed to reduce production of the epithelial sodium channel alpha subunit (αENaC) in the airways of the lung. In patients with CF, increased ENaC activity contributes to airway dehydration and reduced mucociliary transport. In CF lung disease, patients can have difficulty breathing and experience frequent and persistent lung infections. Various human genetic studies have validated ENaC as a potential therapeutic target for CF, but the development of inhaled small molecule ENaC inhibitors has been limited by on-target renal toxicity and short duration of action in the lung.
For further information, see Arrowhead Pharma

Related Informations / Publications

- SEP 2019: Arrowhead Pharmaceuticals Presents Initial Top-Line Clinical Data and Preclinical Data on RNAi Candidates ARO-APOC3 and ARO-ANG3
Link: Press Release
-AUG 2019: Arrowhead Pharmaceuticals Doses First Patient in SEQUOIA Phase 2/3 Study of ARO-AAT for Treatment of Alpha-1 Liver Disease
Results/Comments: SEQUOIA (NCT03945292) is a placebo-controlled, adaptive design Phase 2/3 study to evaluate the safety, efficacy, and tolerability of ARO-AAT administered subcutaneously to patients with AATD associated liver disease
Link: Press Release

m&A - AGREEMENTS

Cognate BioServices announces acquisition of Cobra Biologics

Cognate BioServices, a CDMO specialized in cell and cell-mediated gene therapy products and Cobra Biologics, a leading CDMO specialized in providing manufacturing services for plasmid DNA and viral vector, announced on November 04th that they have entered into a definitive agreement in which Cognate will acquire all of the outstanding share capital of Cobra. Existing Cognate investor EW Healthcare Partners led the financing for the acquisition. The transaction creates an industry-leading enhanced services provider delivering drug development and manufacturing solutions to the global cell and gene immunotherapy and regenerative medicine industries. Together, Cognate and Cobra will be well positioned to leverage their decades of industry knowledge and experience, provide an integrated supply chain for their clients, and expand their global capability to provide better and more scalable solutions to support the ever-changing needs of their clients. For further information, see Cobra Bio

Related Informations / Publications

- OCT 2019: CPI Accelerates Gene Therapy Development with Robust Adeno-Associated Virus Purification System in Partnership with Cobra Biologics and GE Healthcare
Results/Comments: The CRDI UK project was funded by a £570K grant from Innovate UK and focused on optimising an AAV purification process using GE Healthcare Life Sciences’ innovative Fibro™ chromatography material
Link: Press Release
- AUG 2019 : Cognate BioServices Secures Growth Capital Investment from EW Healthcare to Continue to Expand Commercial Manufacturing Capacity and Services for the Cellular Therapies Industry
Link: Press Release
- JUN 2019 : Cognate BioServices receives Statement of Compliance to EU Good Manufacturing Practice for manufacture of Advanced Therapeutic Medicinal Products
Link: Press Release

Dicerna enters agreement with Roche to develop and commercialize DCR-HBVS for the treatment of Chronic Hepatitis B Virus (HBV) infection

Dicerna announced on October 31st a research collaboration and licensing agreement with Roche to develop novel therapies for the treatment of chronic hepatitis B virus (HBV) infection using Dicerna’s proprietary GalXC™ RNAi platform technology. The collaboration will focus on worldwide development and commercialization of DCR-HBVS, Dicerna’s investigational therapy in Phase 1 clinical development. The collaboration also includes the discovery and development of therapies targeting multiple additional human and viral genes associated with HBV infection using the technology platforms of both companies. Under the terms of the agreement, Dicerna will receive $200 million in an initial upfront payment and may be eligible to receive up to an additional $1.47 billion over time for the achievement of specified development, regulatory and commercial milestones. In addition, Dicerna may be eligible to receive royalties based on potential product sales of DCR-HBVS. Dicerna retains an option to co-fund pivotal development of DCR-HBVS worldwide, which if exercised, entitles Dicerna to receive enhanced royalties and co-promote products including DCR-HBVS in the U.S. Dicerna and Roche also agreed to collaborate on the research and development of additional therapies targeting multiple human and viral genes implicated in chronic HBV infection, using technology from both companies, for which Dicerna is eligible to receive additional milestones and royalties on any potential products. For further information, see Dicerna

Dicerna Pharmaceuticals is one of the 230 companies deeply scrutinized in
our latest report "Landscape in...Gene Therapy Companies"

Do not hesitate to click here to get sample pages

Related Informations / Publications

- Nanoscale. 2019 Oct 28;11(40):18806-18824. The role of apolipoprotein- and vitronectin-enriched protein corona on lipid nanoparticles for in vivo targeted delivery and transfection of oligonucleotides in murine tumor models. Chen D et al. Northeastern University, Boston, MA 02115, USA. Link: Abstract
-JUL 2019: Dicerna™ to Begin Clinical Development of DCR-A1AT for Treatment of Patients with Alpha-1 Antitrypsin Deficiency-Associated Liver Disease
Link: Press Relase
- MAY 2019: Dicerna Announces Dosing of First Patient in Phase 1 Clinical Trial of DCR-HBVS for the Treatment of Chronic Hepatitis B Virus
Results/Comments: The Company anticipates human proof-of-concept data from the Phase 1 trial, which is known as DCR-HBVS-101, in the fourth quarter of 2019. In January 2019, Dicerna announced the dosing of the first human volunteer in this Phase 1 study. Link: Press Release
- Expert Opin Drug Deliv. 2018 Jun;15(6):629-640. Recent preclinical and clinical advances in oligonucleotide conjugates. Craig K et al. School of Pharmacy, Northeastern University, Boston, MA, USA.
Link: Abstract

Roivant, Sumitomo alliance to target cystic fibrosis gene therapy

Sumitomo Dainippon Pharma, a leading Japanese pharmaceutical company, and Roivant Sciences, a technology-enabled healthcare company, today announced that they have signed a definitive agreement for the creation of a novel and broad Strategic Alliance and to form a new company owned and supported by Sumitomo Dainippon Pharma. As previously announced, this will include the transfer to Sumitomo Dainippon Pharma of Roivant's ownership interests in five of their biopharmaceutical companies ("Vants") and access to Roivant's proprietary technology platforms, DrugOme and Digital Innovation. In addition, Sumitomo Dainippon Pharma will take an equity stake of over 10% of shares outstanding in Roivant and will have options to acquire Roivant's ownership interests in up to 6 additional Vants by 2024. These 11 Vants collectively have more than 25 innovative clinical programs, with multiple potential product launches expected from 2020 to 2022. The transaction will be subject to customary closing conditions and any required governmental approvals. Roivant will receive USD $3 billion from Sumitomo Dainippon Pharma as a payment to enter the Alliance. Exercise of the Options by Sumitomo Dainippon Pharma will trigger additional payments to Roivant. In addition, Sumitomo Dainippon Pharma will enter separate strategic client relationships with Datavant and Alyvant to augment development and commercialization activities. For further information

Related Informations / Publications

-Hum Mol Genet. 2019 Oct 1;28(R1):R88-R94. Advances in gene therapy for cystic fibrosis lung disease. Yan Z et al. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Results/Comments: The outcomes of CF lung gene therapy trials will likely inform productive paths toward gene therapy for other complex genetic disorders, while also advancing treatments for all CF patients. Link: Abstract
- SEP 2019: Roivant lines up $3B upfront in Sumitomo Dainippon deal Results/Comments: As part of a $3 billion deal brokered with Roivant Sciences, Japanese drugmaker Sumitomo Dainippon will gain ownership of a newly unveiled biotech focused on developing gene therapies for cystic fibrosis
Link: BioPharma Dive
- Genes Dis. 2018 Nov 25;6(2):97-108. Delivering on the promise of gene editing for cystic fibrosis. Hodges CA et al. Case Western Reserve University, Cleveland, OH, USA Results/Comments: The advances made in gene therapy may help develop delivery vehicles for gene editing, although major improvements are needed
Link: Abstract - Full Text

Vineti and WuXi AppTec Advanced Therapies collaborate to simplify manufacturing supply chain for advanced therapies

Vineti, a leading provider of a digital platform of record for personalized therapies, and WuXi AppTec Advanced Therapies, the advanced therapies BU of the chinese CDMO WuXi AppTec, said on November 05th that they have entered into a collaborative agreement to unite Vineti's ordering and traceability platform directly with WuXi's manufacturing facilities in order to bring an end-to-end solution to mutual customers. The goal for the collaboration is to leverage platforms from both WuXi Advanced Therapies and Vineti, such that more novel therapies are able to be developed, manufactured, tested and released faster and with greater predictability, compliance and patient safety to benefit patients worldwide. Vineti is the first commercial, configurable cloud-based platform to expand patient access to life-saving cell and gene therapies. Vineti was co-founded by GE and the Mayo Clinic to solve the key challenges patients, medical providers, biopharmaceutical companies and regulators face in the delivery and commercialization of individualized therapies. Now a fully independent company, Vineti offers a digital platform of record to integrate logistics, manufacturing and clinical data for personalized therapies. The Vineti software solution aligns and orchestrates the cell and gene therapy process and improve product performance overall. The Vineti platform supports the full continuum of patient-specific therapies, including cancer vaccines and autologous and allogeneic therapies. For Further Information

Related Informations / Publications

- OCT 2019: Cell & Gene Therapies Require the Right Tracking Solution
Link: Clinical Leader
-SEP 2019: Vineti, Cryoport partner to extend end-to-end cell therapy logistics offering Link: Outsourcing Pharma