Cell and Gene Therapy Business Outlook

 

A New Publication Covering The CELL AND GENE THERAPY INDUSTRY

The Best Way to Keep up with the Growing Cell and Gene Therapy Industry

From Science and Medicine Group, the company behind Instrument Business Outlook, Kalorama Information, SDi and other publications, comes a new publication: Cell and Gene Therapy Business Outlook.

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With thousands of potential therapies on the market, cell and gene therapy promises future potential for pharmaceutical developers and those serving them.

  • A new twice-monthly publication dedicated to cell and gene therapy, Cell and Gene Therapy Business Outlook will offer the following:
  • Market Sizing and Forecasting of CGT Markets in Every Issue
  • Executive News Summaries – What is Happening in CGT Markets and Why It Matters
  • Deals Between CGT Companies Tracked in Every Issue
  • Important Science That Will Shape Tomorrow’s Business
  • Updates on Pipelines and Important Clinical Trials
  • Cell and Gene Therapy Tools, CMOs, Manufacturing Developments
  • Market Analysis of a Cell and Gene Therapy Segment in Every Issue

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There are many websites, publications and sources on cell therapy. Cell and Gene Therapy Business Outlook differs from these sources in that it is created by market researchers and editors focused on business opportunity. Each issue will track the market size and potential for a key market segment.

Who Is Dealing with Whom? Tracking of Cell and Gene Company Deals In Every Issue.

There is a never-ending stream of activities in this market. How can you keep up? Each issue of Cell and Gene Therapy Business Outlook will keep track of mergers, investments, licensing, technology transfers and partnerships in the industry. Each issue of Cell and Gene Therapy Business Outlook contains an updated CGT Recent Deals Table with information on these important events.

Future issues will also analyze of the number of deals and increases or decreases in activity as a measure of business. You’ll never miss an important happening with Cell and Gene Therapy Business Outlook. Also, the Recent Deals Table is a great resource for tracking companies in the market.

The News That Matters

Edited by Blake Middleton, a professional CGT researcher and former Staff Research Associate at UCLA Department of Pharmacology, Cell and Gene Therapy Business Outlook is designed to provide the most relevant news. Included is news that could affect business decisions near-term. Cell and Gene Therapy Business Outlook also explains the relevant science.
With a focus on what the recent news of the day means for business, our curated news and news analysis means that you and your organization can be confident you won’t miss an important development in cell and gene therapy.

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Convenient and Cost-Effective Seat-Based Pricing: Pricing depends on the number of users. Subscriptions can be as low as $2,200 annually for a limited one-person (single user) subscription.

Open up access: If more than one person will be reading, you can unlock access to other members of your organization. It’s easy to do: team subscription prices are as little as $4,995 annually for up to five readers. Larger team? Other licenses are available. Consult our website.  Convenient and Cost-Effective Seat-Based Pricing: Pricing depends on the number of users. Subscriptions can be as low as $2,200 annually for a limited one-person (single user) subscription.


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THE CELL AND GENE THERAPY MARKET IN ONCOLOGY is $1,582M

MARKET SIZE: The global market for cell and gene therapy for oncology reached $1,582 million in 2020 and is expected to climb to $2,744 for 2021.

There are over 100 different types of cancer; some of the more prominent include lung, breast, brain, blood, prostate and colon cancer. The immune system plays a primary role in the body’s defense against malignancy. Although a tumor is derived from the body’s own cells and is expected to possess proteins that are recognized as self and nonantigenic, neoplastic cells can express antigens that are not recognized as self. These cells can often be eliminated by the immune system.

FORECAST: projected to increase to $7,391 in 2025; $17,490 million by 2030.

Treating cancer is difficult because it is not a single disease and because all the cells in a single tumor do not behave in the same way. Although most cancers are thought to be derived from a single abnormal cell, by the time a tumor reaches a clinically detectable size, the cancer may contain a diverse population of cells.

Market Forecast:  Strong increases in the CAR-T therapy market, increasing from just $16 million in 2017 to $1,081 million in 2020 and projected to increase to $7,391 in 2025; $17,490 million by 2030.  Blood cancers are the leading driver in the segment, representing 68% of total sales. This is expected to be the primary segment through the forecast, representing 80% of sales by 2025 and 80% in 2030.  The United States and Europe are the largest markets due to overall product approvals and cost associated with the therapies. The US market represented nearly 77%, while Europe represented 19% in 2020.  Gilead and Novartis combined represent 68% of the market for cell and gene therapy in oncology.  Industry refocuses on oncology cell and gene therapies in a post-pandemic arena, returning to pre-pandemic growth.

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AAV CAPSID DISCOVERY UPDATE

Adeno-associated viruses (AAV) are small human viruses which provoke only a mild immune response and are not known to cause any human disease. AAVs are quite simple in organization, possessing a small (4.7kb) single-stranded DNA genome with only two open reading frames (ORFs), rep and cap, flanked by short (145 base) inverted terminal repeats (ITRs). The rep ORF encodes multiple overlapping sequences for proteins required for replication, and the cap ROF does the same for capsid proteins, which are the proteins forming the outer viral protein coat. These genes alone are not sufficient for viral replication, and AAVs require co-infection with a second, helper virus (such as an adenovirus or HSV) to supply the remaining gene products for replication (hence the name adeno-associated virus).


Gene therapy AAV vectors are further modified to remove the rep and cap genes from the viral genome (along with their promoters and polyadenylation signal), replacing them with a therapeutic expression cassette. Production of recombinant AAV vectors in cell lines requires the rep and cap genes to be supplied by a plasmid transfected in trans, in addition to the genes supplied by the helper virus. None of these externally supplied viral genes are packaged into the final construct, so the resulting viral delivery vehicle consists only of the therapeutic cassette encased in an AAV capsid, without any viral genes present. The gene therapy vector is therefore incapable of replication, even with co-infection by a suitable helper virus.
In addition to their safety, AAV vectors possess many features which make them attractive gene therapy candidates. They have extremely low immunogenicity, they can infect both dividing and non-dividing cells, and they can persist outside the genome to offer stable, long-term expression without the risks associated with host genome integration.

AAV vectors also suffer from several shortcomings, however:
• Because of their wide distribution, many individuals have already been exposed to naturally occurring AAV serotypes and produce immune responses against them.
• AAV vectors cannot reach most tissues efficiently, and do not spread easily within those tissues if they do.
• Vectors will preferentially target some cell types but not others.
• Transduction efficiency is often extremely low.

Each of these shortcomings can be addressed by innovations in capsid structure. In addition to protecting the DNA payload, the capsid is responsible for binding to specific receptors on the target cell and safely delivering the DNA payload to the cell machinery that so will be transported to the nucleus. Viral packaging efficiency, host immunological response, tissue and cell type specificity, and transduction efficiency are all determined by the capsid serotype. Unfortunately, initial gene therapy experiments were restricted to a handful of natural AAV serotypes which had limited tropism in many human cell types. Common serotypes also present problems with pre-existing immunity (PEI), as up to 90% of the human population have already been exposed to at least one AAV serotype. For these reasons, novel capsid discovery is a current hotbed of gene therapy research.

More information on this topic can be found in the latest issue. SUBSCRIBE TODAY

 

THE LATEST NEWS FROM CELL AND GENE THERAPY OUTLOOK

 

There have been a number of recent developments in cell and gene therapy, as detailed in our bimonthly newsletter, Cell and Gene Therapy Business Outlook.

  • Kite Pharma, a Gilead Company based in Santa Monica, CA, has announced that the European Commission (EC) has granted approval for its chimeric antigen receptor (CAR) T cell therapy Tecartus (brexucabtagene autoleucel) for the treatment of adult patients 26 years of age and above with relapsed or refractory (R/R) B-cell precursor acute lymphoblastic leukemia (ALL).  Tecartus is an autologous, CAR T cell therapy targeting CD19, an antigen ubiquitously expressed on B cells.  Last year Tecartus was approved by the U.S. FDA for the same indication.
  • CellOrigin Biotech, an immune cell therapy company based in Hangzhou, China, and Qilu Pharmaceutical, a pharmaceutical company based in Jinan, China, have announced a collaboration to develop, manufacture, and commercialize off-the-shelf induced pluripotent stem cell (iPSC)-derived chimeric antigen receptor macrophages (CAR-iMAC) for cancer immunotherapy.  CellOrigin’s developmental pipeline currently includes an iPSC-derived natural killer (iNK) + monoclonal antibody therapy candidate for the treatment of hematological malignancies, a CAR-iNK cell therapy candidate for solid tumors, and several CAR-iMAC cell therapy candidates for solid tumors.
  • The University of Sydney has announced an unprecedented $478 million investment to build a leading biomedical precinct in New South Wales, its largest ever capital investment. The Sydney Biomedical Accelerator (SBA) will establish a 36,000 square-meter health, education, and research precinct, to be co-located at Royal Prince Alfred Hospital and the University’s Camperdown campuses.  The New South Wales Government contributed $143.3 million to the project, and other funding includes $73 million in philanthropy to the University of Sydney and a $20 million donation from the Susan and Isaac Wakil Foundation to establish The Isaac Wakil Biomedical Building.   The SBA will support over 1200 biomedical researchers and clinician scientists, including over 800 university laboratory researchers and PhD students, with occupation anticipated to begin in 2026.
  • Cytiva, a life sciences company based in Marlborough, MA, and Caring Cross, a 501(c)(3) non-profit organization focused on developing advanced medicines accessible to all patients, have announced a partnership to develop a chimeric antigen receptor (CAR)-T cell therapy for people with HIV in low-to-middle-income nations.  Cytiva will provide equipment and software packages, including the Sepax C-Pro, (a place of care instrument which can reduce CAR-T processing times by automatically isolating, concentrating, washing, and diluting cellular products) and the VIA Thaw and VIA Freeze instruments (which streamline freezing and thawing processes while minimizing the contamination risks associated with traditional water baths).  Caring Cross has developed a duoCAR-T cell therapy candidate targeting HIV which can both eliminate HIV-infected cells and protect CD4-T cells from HIV infection in in vitro studies and animal models, and the therapy is currently being evaluated in a Phase I/II clinical trial.  Caring Cross is also developing a stem cell gene therapy for the treatment of sickle cell disease (SCD) and beta-thalassemia.
  • Arbor Biotechnologies, a gene editing company based in Cambridge, MA, has announced that it has entered an agreement with Acuitas Therapeutics, a leader in the development of lipid nanoparticles (LNP) based in Vancouver, BC, to develop therapies for rare liver diseases.  Arbor specializes in discovering and developing novel gene editors using its machine learning/AI driven discovery platform, and has an established pipeline of rare liver disease programs in preclinical development.  The two companies plan to combine Acuitas’ optimized LNP delivery technology with Arbor’s proprietary CRISPR-based in vivo gene editing therapies targeting rare liver diseases to accelerate these programs into the clinic.
  • ElevateBio, a cell and gene therapy technology company based in Cambridge, MA, and the University of Pittsburgh have announced a long-term strategic partnership to develop cell and gene therapies.  The 30-year agreement will establish ElevateBio’s next BaseCamp process development and Good Manufacturing Practice (GMP) manufacturing facility at the Pitt BioForge BioManufacturing Center at Hazelwood Green.  The University of Pittsburgh created the Pitt BioForge biomanufacturing facility with a $100 million grant from the Richard King Mellon Foundation in November 2021.  The new BaseCamp facility will be equipped with gene editing and  induced pluripotent stem cell (iPSC) technologies, as well as cell, vector, and protein engineering capabilities, and is expected to generate more than 170 full-time jobs.
  • ElevateBio has also announced a partnership with the California Institute for Regenerative Medicine (CIRM) to advance regenerative medicine therapies through CIRM’s Industry Alliance Program.  For its part, ElevateBio will supply its induced pluripotent stem cells (iPSC) lines to academic and commercial beneficiaries of CIRM Discovery and Translational Grants, along with viral vector technology, process and analytical development, and Good Manufacturing Practice (GMP) manufacturing capabilities. CIRM has received $5.5 billion in funding from the state of California, and has already funded over 161 regenerative medicine research projects and 81 clinical trials.
  • BioCardia, a cell therapy company based in Sunnyvale, CA, has announced it has entered an agreement with BlueRock Therapeutics, an engineered cell therapy company (and subsidiary of Bayer AG) based in Cambridge, MA, to use BioCardia’s minimally invasive biotherapeutic catheter delivery systems to deliver BlueRock’s induced pluripotent stem cell (iPSC)-derived cell therapy product candidates locally to the heart for the treatment of heart failure. Under the time-limited agreement, BioCardia will receive an up-front payment, and BlueRock will have an option to negotiate a non-exclusive worldwide license to use BioCardia’s biotherapeutic delivery systems to deliver certain cell types for cardiac indications.
  • Gensaic, a gene therapy spinout from MIT based in Cambridge, MA, has announced a strategic collaboration agreement with Ovid Therapeutics, a gene therapy company based in New York, NY, to develop up to three genetic medicines for central nervous system (CNS) indications of interest to Ovid using its proprietary phage-derived particle (PDP) platform.  Under the terms of the agreement, Gensaic retains full rights to its PDP platform technology, while Ovid will have the right to license and develop any gene therapies resulting from the collaboration.  Ovid has also invested $5 million in Gensaic and retained rights to invest in future rounds.  Gensaic’s PDP platform is a modular system derived from the M13 bacteriophage (a filamentous virus which infects bacteria) and consists of three engineerable capsid proteins and a minimal phage DNA (mpDNA) genome capable of delivering of genetic payloads larger than 20 kb.  The platform combines phage display technology with directed evolution to engineer tissue-specific, immune-privileged, and redosable delivery vehicles that can be easily manufactured in bacterial culture.  Gensaic is currently focused on developing delivery systems  targeting muscle, respiratory, and CNS tissues.
  • Cambridge, MA-based bluebird bio has announced that the U.S. FDA has approved ZYNTEGLO (betibeglogene autotemcel, or beti-cel), its one-time gene therapy for the treatment of beta‑thalassemia in adult and pediatric patients who require regular red blood cell (RBC) transfusions.  Beta-thalassemia is a rare genetic blood disease caused by mutations in the HBB gene encoding β-globin, a major component of hemoglobin A (HbA) resulting in reduced or absent adult hemoglobin production. In Zynteglo therapy, a patient’s hematopoietic stem cells (HSCs) are harvested, then purified and transduced them with a lentiviral vector (LVV) carrying a modified form of the HBB gene encoding β-globin.  The cells are then re-infused back into the patient, where they engraft to the bone marrow and produce new blood cells expressing the modified HBB gene, enabling the cells to make normal or nearly normal levels of adult hemoglobin. The therapy is the first ex vivo lentiviral vector gene therapy to be approved in the U.S. for the treatment of beta-thalassemia. (See Cell and Gene Therapy Business Outlook vol. 2, issue 1, p. 13 for more on bluebird bio and Zynteglo, its gene therapy for beta-thalassemia.)    
  • GentiBio, a biotherapeutics company based in Boston, MA, has announced that it has entered a collaboration with Bristol Myers Squibb, based in New York, NY, to develop engineered regulatory T (Treg) cell therapies for the treatment of patients with inflammatory bowel diseases (IBD).  GentiBio specializes in engineered Treg cell therapies, which have the potential to treat autoimmune and inflammatory diseases such as IBD by re-establishing immune tolerance in a tissue-specific manner.  Under the multi-year collaboration, GentiBio will produce stable, disease-specific engineered Tregs against multiple targets utilizing its modular engineered Treg platform and scalable manufacturing process, and Bristol Myers Squibb will have the right to bring up to three programs resulting from the collaboration into the clinic.  In exchange, Bristol Myers Squibb has made an undisclosed cash payment to GentiBio up front, and GentiBio is eligible to receive up to $1.9 billion in development and sales milestones, plus royalties.

There have been a number of recent developments in cell and gene therapy, as detailed in our bimonthly newsletter, Cell and Gene Therapy Business Outlook.

  • Prescient Therapeutics, a clinical stage oncology company based in Melbourne, Australia, has signed a five-year manufacturing agreement with Q-Gen Cell Therapeutics, a specialist cell therapy manufacturer based at the QIMR Berghofer Medical Research Institute in Brisbane, to produce Prescient’s OmniCAR cell lines for use in clinical trials.  The OmniCAR platform is a modular chimeric antigen receptor (CAR) system: T cells are transduced to express a SpyCatcher universal immune receptor, which can then bind to any desired targeting ligand equipped with a SpyTag motif.  The system enables tremendous control over T cell activity after infusion into the patient, including the ability to target multiple antigens, switch targets at will, and ramp T cell activity up or down.  The contract with Q-Gen Cell covers lentiviral transduction of T cells with the SpyCatcher vector, the arming of OmniCAR transduced T cells with SpyTagged binders, and the use of Prescient’s CellPryme-M platform, a high-performance manufacturing process.  Prescient has also signed an agreement Waltham, MA-based Thermo Fisher Scientific to develop and commercialize a scalable version of the OmniCAR platform, evaluating the potential use of automated, closed manufacturing systems and non-viral methods for large-scale applications.
  • National Resilience, a biomanufacturing company based in San Diego, CA, has announced a collaboration with Mayo’s Center for Regenerative Medicine in Rochester, Minnesota, to establish embedded process development, analytical development, and quality control labs at the Rochester site, and to jointly develop cell therapies and other advanced therapeutics derived from biologics, with the goal of bringing these therapies into the clinic.  The collaboration hopes to create a business incubator and attract third-party biotech companies to collaborate on process and analytical development and to sponsor clinical trials for new therapies.  Resilience has worked to establish a broad network of facilities across North America, occupying over 1 million square feet of manufacturing space with more than 1,600 employees.
  • RoosterBio, a supplier of human mesenchymal stem/stromal cells (hMSC) and extracellular vesicle (EV) products based in Frederick, MD, and AGC Biologics, a global biopharmaceutical contract development and manufacturing organization (CDMO) based in Seattle, WA, have announced a strategic partnership to develop hMSC and exosome therapeutics.  RoosterBio will provide expertise in genetic engineering of cells and exosomes, upstream processing, downstream purification, and analytical characterization of potential therapies.  AGC will provide full process development, cGMP manufacturing, quality control, and regulatory services up through Phase I/II clinical trials, with the potential to scale to Phase III trials and even commercial production.
  • EV Biologics, a nanoparticle-based  therapeutics (nanotherapeutics) company based in Cheyenne, WY, has announced that it has launched Excyte, a wholly owned subsidiary with a $100 million valuation.  EV Biologics is focused on developing the therapeutic potential of extracellular vesicles (EVs), particularly exosomes produced by mesenchymal stem cells (MSCs). Excyte will develop biomanufacturing, bioengineering, bioanalytic, and machine learning technologies to build a development platform for nanotherapeutic treatments targeting any indication.  The new company plans to raise $2.5 million in initial capital, and has already achieved 20% of that goal.  The funding will be used to evaluate small-scale automated bioreactor platforms and develop scalable biomanufacturing technologies for stem cell-derived nanotherapeutics. Excyte will also analyze secretome products and nanoparticle fractions produced by EV Biologics’ mesenchymal stem/stromal cell banks.  EV Biologics’ CEO, Daniel Mckinney, says the company’s ambition is to restore health, combat aging, and provide a longer health span.
  • WuXi Advanced Therapies, a contract testing, development, and manufacturing organization (CTDMO) based in Philadelphia, PA, has announced a licensing agreement with Janssen Biotech, a subsidiary of Johnson & Johnson based in Horsham, PA, for WuXi’s high-performance TESSA technology platform.  The agreement will also grant Janssen access to WuXi’s proprietary HEK293 suspension cell line.   WuXi says the TESSA manufacturing platform can produce 10 times more adeno-associated virus (AAV) than traditional AAV manufacturing systems, and at significantly higher quality.
  • Sarepta Therapeutics, a genetic medicine company based in Cambridge, MA, has announced that it has exclusively licensed the MyoAAV platform from Broad Institute of MIT and Harvard for Duchenne muscular dystrophy (DMD) and four other neuromuscular and cardiac indications.  The MyoAAV platform encompasses a novel group of adeno-associated viruses (AAV) with capsids optimized for muscle delivery.  Compared to natural AAV serotypes, MyoAAV capsids have demonstrated improved gene expression in multiple skeletal muscles (25-50 fold) and cardiac muscle (10-15 fold), with 50% lower delivery to the liver. Under the agreement, Sarepta will receive worldwide commercial rights for DMD and the other four neuromuscular and cardiac indications, with exclusive options for additional targets. In exchange, Broad Institute will receive an upfront payment in addition to future royalties and milestone payments.  Further financial details of the agreement were not disclosed.
  • RoslinCT, a cell and gene therapy contract development and manufacturing organization (CDMO) based in Edinburgh, UK, and Lykan Bioscience, a cell therapy CDMO based in Hopkinton, MA, have announced that they have entered into a business combination agreement to form a global advanced therapies CDMO.  Lykan is equipped with a 64,000 square-foot cell therapy manufacturing facility housing 16 cGMP processing suites at its Hopkinton site, which is expected to be fully operational by the end of 2022. RoslinCT plans to expand capacity at its 40,000 square-foot manufacturing facilities in Edinburgh with 8 cGMP suites.  Earlier this year, Global Healthcare Opportunities (GHO Capital Partners) announced an investment in RoslinCT, and will now make a majority investment in Lykan and support the combined entity. WindRose Health Investors, prior majority owner of Lykan, have also reinvested in the combined entity with Lykan Management.
  • ElevateBio, a cell and gene therapy technology company based in Cambridge, MA, and Boston Children’s Hospital have announced a new spinoff company to develop stem-cell-based, allogeneic chimeric antigen receptor T (CAR-T) cell therapies.  The yet to be named company is based on research from the laboratory of George Daley, MD, PhD, head of stem cell transplantation at Boston Children’s Hospital, and is the first company to spin out from a five-year collaboration between Boston Children’s Hospital and ElevateBio aimed at the development of cell and gene therapies.  Typically, induced pluripotent stem cells (iPSCs) tend to give rise to immature, embryonic blood cell types, but Daley’s team was able to derive mature αβ T cells from iPSCs by repressing the histone methyltransferase enzyme EZH1.  The resulting T cells, which they call EZ-T cells, show enhanced cytotoxicity, elevated cytokine production, superior persistence, and more efficient tumor clearance in preclinical studies when compared to conventionally produced iPSC-derived T cells.  A paper describing this new technology was published in the Aug 4th, 2022, issue of Cell Stem Cell.