Industry Update: Business Development
Latest business developments compiled from January 1 — February 29 2016
Latest business developments in the field of stem cell research and
regenerative medicine compiled from publicly available information and
press releases from non-academic institutions from January 1 — February 29 2016, scheduled to be published in Volume 11 Issue 4 of Regenerative Medicine.
Collaborations, partnerships & alliances
Co-development agreement: Kiadis Pharma and LLS
Kiadis Pharma (Netherlands; www.kiadis.com) has entered into a partnership with The Leukemia & Lymphoma Society (LLS; NY, US; www.lls.org) under which LLS will fund the Phase II development of Kiadis Pharma’s lead product, ATIR101â„¢, through an equity investment of approximately US$ 1 million. LLS is investing via its Therapy Acceleration Program, a strategic initiative to partner directly with biotechnology companies to help accelerate the development of promising therapies. The company intends to continue this trial into a randomized controlled Phase III pivotal study that is planned to start later this year. This ongoing Phase II trial is investigating the repeated dosing of ATIR101â„¢ as an adjunctive treatment to a T-cell depleted haploidentical hematopoietic stem cell transplantation in adult patients with acute myeloid leukemia or acute lymphoblastic leukemia. The trial is conducted under an Investigational New Drug (IND) of the US FDA and is set up to enroll patients in the USA, Canada, Belgium and the UK. Additional information about the clinical trial is available at http://clinicaltrials.gov (ID: NCT02500550).
Co-development agreement: Neon and NKI
Neon Therapeutics (MA, US; www.neontherapeutics.com) has entered into a collaborative research agreement with the Netherlands Cancer Institute’s (NKI; the Netherlands, www.nki.nl) Antoni van Leeuwenhoek Hospital (www.avl.nl) and the Amsterdam Biotherapeutics Unit (www.ambtu.nl). Under the terms of the agreement, Neon Therapeutics and NKI will combine complementary capabilities to develop personalized T cell therapeutics. Building on this expertise, the project aims to generate neo-antigen-specific T cells for the personalized treatment of cancer. Neon Therapeutics is an immuno-oncology company focused on developing novel therapeutics leveraging neo-antigen biology to treat cancer.
Co-development agreement: PDS Biotechnology and National Cancer Institute
PDS Biotechnology (IN, US; www.pdsbiotech.com) has signed a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI; www.cancer.gov), an Institute of the US NIH. Under the CRADA, PDS and NCI aim to co-develop several immunotherapies through Phase II clinical trials to be initiated in 2016 and 2017, utilizing combinations of Versamune® with NCI-and PDS-sourced Tumor-related antigens in prostate, breast, and Human Papilloma Virus-related cancers. Versamune is a clinical stage and synthetic lipid-based immunotherapy platform.
Co-development and manufacturing agreement: Angiocrine and Terumo
Angiocrine Bioscience (NY, US; www.angiocrinebioscience.com) announced a three-year collaboration agreement with Terumo BCT (Japan; www.terumobct.com) to implement Terumo BCT’s Quantum Cell Expansion System as a manufacturing platform for its ECELâ„¢ technology and therapeutic candidates. The Quantum system streamlines the cell culture process and furthers the research and development of Angiocrine’s cell therapy products by enhancing process scalability, increasing reproducibility and reducing costs. The combination of protocol flexibility and process control through automation provides a significant advantage over manual flask-based methods and positions the Quantum system ideal for a range of production scenarios from bench top research to commercial manufacturing.
Collaboration agreement: Fibrocell and Intrexon
Fibrocell Science (PA, US; www.fibrocell.com) and Intrexon (VA, US; www.dna.com) announced an Exclusive Channel Collaboration for the development of genetically-modified fibroblasts to treat chronic inflammatory and degenerative diseases of the joint, including arthritis and related conditions. Through the collaboration, Fibrocell’s proprietary fibroblast platform will be combined with Intrexon’s cellular engineering capabilities to generate cell-based therapeutics that have been modified to express one or more proteins at sites of joint inflammation helping overcome the limitations of existing treatment approaches for chronic inflammatory and degenerative diseases of the joint. Under the terms of the agreement, Intrexon will receive a technology access fee of US$ 10 million in cash and reimbursement for all research and development costs. The agreement also provides for regulatory and commercial milestone payments to Intrexon for each collaboration product of up to US$ 30 million and US$ 22.5 million, respectively, as well as a low double-digit royalty based on the net sales from collaboration products.
Collaboration agreement: Surface Oncology and Novartis
Surface Oncology (MA, US; www.surfaceoncology.com) has entered into a broad strategic collaboration with Novartis (Switzerland; www.novartis.com) to develop immunotherapeutics targeting the tumor microenvironment and the interface of innate and adaptive immunity. Under the terms of the agreement, Surface is eligible to receive up to US$ 170 million in upfront, equity, and nearterm milestone payments. Novartis will gain exclusive access to Surface’s current pipeline of novel cancer immunotherapies, including an exclusive worldwide license to its leading program and options to license up to three additional programs from the existing portfolio, exercisable as IND. Surface is eligible to receive clinical and commercial milestones and up to doubledigit royalties on product sales. Surface also has the option to retain US development and commercialization rights for at least half of the collaboration’s programs.
Collaboration agreement expansion: GSK and Adaptimmune
Adaptimmune Therapeutics (UK; www.adaptimmune.com) and GlaxoSmithKline (GSK; UK, www.gsk.com) have expanded the terms of their strategic collaboration agreement to accelerate Adaptimmune’s lead clinical cancer program, an affinity enhanced T-cell immunotherapy (GSK3377794) targeting NYESO1, toward pivotal trials in synovial sarcoma. Adaptimmune and GSK announced a strategic collaboration and licensing agreement in June 2014 for up to five programs. Under the terms of the expanded agreement, the companies will accelerate the development of Adaptimmune’s NYESO therapy into pivotal studies in synovial sarcoma and will explore development in myxoid round cell liposarcoma. Additionally, the companies may initiate up to eight proof-of-principle studies exploring combinations with other therapies, including checkpoint inhibitors. According to the expanded development plan, the studies will be conducted by Adaptimmune with GSK effectively funding the pivotal studies and sharing the costs of the combination studies via a success based milestone structure.
Collaboration extension: Bone Therapeutics and Kasios
Bone Therapeutics (Belgium; www.bonetherapeutics.com) and Kasios (France, www.kasios.com) extended their collaboration on developing spinal fusion integrated products. Under the new collaboration, the companies aim to combine Bone Therapeutics’ ALLOB® cells with Kasios’ spinal fusion cage containing a 3D-bioprinted synthetic matrix (or ‘waffle’). The goal of this combined product is to simplify the surgical procedure and accelerate the fusion process. Spinal fusion is considered to be the gold standard for treating a broad spectrum of degenerative spine disorders, including degenerative disc disease, to relieve pain and improve function. Spinal fusion consists of bridging two or more vertebrae with the use of a cage and graft material, traditionally an autologous or synthetic bone graft, for fusing an unstable portion of the spine or immobilizing a painful vertebral motion segment. Although this procedure is routine, failure to achieve fusion between the vertebrae is quite common. Bone Therapeutics aims to accelerate the fusion process and increase success rates of the surgery using its allogeneic bone cell therapy product, ALLOB. The companies ultimately aim to provide an integrated ready-to-use product for surgeons that simplifies the procedure and reduces operation time.
Licensing agreement: ATCC and Broad Institute
ATCC (VA, US; www.atcc.org) has licensed Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 gene editing technology from the Broad Institute (MA, US; www.broadinstitute.org). ATCC plans to use the gene editing technology to develop a portfolio of new products and services to support basic and translational research. CRISPR gene editing allows for precise genetic modifications. This capability allows researchers to create more relevant and predictable in vitro disease models, which will enable a greater level of success in drug discovery, development, and screening. The first ATCC product developed using the licensed technology is the EML4ALK FusionA549 Isogenic Cell Line derived from the parental A549 non-small cell lung cancer cell line, which is known as a work horse for in vitro and in vivo lung cancer research.
Licensing agreement: Creative Medical Technologies and LA Biomed
Creative Medical Technologies, Inc. (AZ, US; www.creativemedicalhealth.com) has signed a license agreement with LA BioMed (CA, US; www.labiomed.org) granting exclusive rights for US patent application #14/508763, covering the use of stem cells for treatment of male infertility. Creative Medical Technologies plans to accelerate clinical development of the patent application by leveraging its clinical expertise in the area of autologous bone marrow cell therapies, in part gained from its ongoing clinical trial utilizing this approach for treatment of erectile dysfunction.
Licensing agreement: ViaCyte and Janssen
ViaCyte (CA, US; www.viacyte.com) and Janssen Biotech (PA, USA; www.janssenbiotech.com) have agreed to consolidate the assets of the Janssen Beta-Logics group into ViaCyte. The agreement provides ViaCyte with an exclusive license to all Beta-Logics intellectual property in the field of metabolic disease, including diabetes, and the transfer of related assets to ViaCyte.
Manufacturing agreement: Asterias and Cancer Research UK
Asterias Biotherapeutics, Inc. (CA, US; www.asteriasbiotherapeutics.com) has completed the transfer of its manufacturing processes to produce AST-VAC2 to Cancer Research UK (UK; www.cancerresearchuk.org). AST-VAC2 is an innovative immunotherapy product that contains mature dendritic cells derived from pluripotent stem cells. These allogeneic AST-VAC2 cells are engineered to express a modified form of telomerase, a protein widely expressed in tumor cells, but rarely found in normal cells. The modified form of telomerase permits enhanced stimulation of immune responses to the protein. The AST-VAC2 dendritic cells instruct the immune system to generate responses against telomerase which will target tumor cells. To accelerate clinical development of AST-VAC2, Asterias has an ongoing partnership with Cancer Research UK and Cancer Research Technology, the charity’s development and commercialization arm, to execute the first clinical trial of AST-VAC2. As part of this partnership, Cancer Research UK will perform cGMP manufacture of AST-VAC2 at their Biotherapeutics Development Unit. Upon successful completion of AST-VAC2 production campaigns, Cancer Research UK’s Centre for Drug Development (CDD) will submit a Clinical Trial Authorisation application to the UK regulatory authorities for a Phase 1/2 clinical trial in non-small cell lung cancer, which will be sponsored, managed and funded by CDD.
Manufacturing agreement: Cellectis and CELLforCURE
Cellectis (France; www.cellectis.com) has entered into a new agreement for the cGMP manufacturing of UCART123 clinical batches, Cellectis’ lead product candidate, with CELLforCURE (France; www.cellforcure.com). CELLforCURE will be in charge of implementing cGMP manufacturing processes designed and developed by Cellectis. Pursuant to a second agreement CELLforCURE will be responsible for the manufacturing of cGMP clinical batches for Universal Chimeric Antigen Receptor T-Cells (UCART) 123, the lead engineered T-cell product candidate in Cellectis’ wholly owned portfolio. UCART123 targets CD123, an antigen expressed on the surface of cancer cells in malignancies, such as acute myeloid leukemia and blastic plasmacytoid dendritic cells neoplasm. UCARTs are “off-the-shelf” allogeneic product candidates. Peripheral Blood Monoculear Cells from healthy donors are transduced and genetically edited with Cellectis’ TALEN® technology to seek and destroy cancer cells
Partnership and licensing agreement: Healios and Athersys
Healios (Japan; www.healios.co.jp/en) and Athersys (OH, USA; www.athersys.com) have announced a partnership and license agreement for the development of regenerative medicine products that will be developed and marketed in Japan by Healios, making use of Athersys’ proprietary, patented stem cell product, MultiStem® cell therapy. Under the term of the agreement, the contract has two aspects. One aspect is exclusive licensing for domestic development and distribution of products used in cellular therapy for ischemic stroke making use of the MultiStem stem cell product. The second aspect is licensing for research and development of multipotent adult progenitor cells (MAPC®), a primary component of the MultiStem product, as a material for the manufacturing of “organ bud” products for regenerative medicine targeting liver disease or dysfunction. MultiStem is an “off-the shelf” stem cell therapy created by Athersys, that is believed to convey therapeutic efficacy through suppressing inflammation and immune reactions, and stimulating the formation of neuroprotective substances.
Research and licensing agreement: ImmunoCellular and Stanford
ImmunoCellular Therapeutics (CA, US; www.imuc.com) has entered into an agreement with Stanford University (CA, USA; www.stanford.edu) for an option to evaluate and license intellectual property related to the identification of T cell receptors (TCRs). Creation of a pure population of T cells, based on targeted screening for specific features, such as affinity to tumor antigens and anti-tumor activity, enables isolation of a single population of TCRs, which can then be sequenced. The DNA from these isolated TCRs can be transferred into stem cells, such as hematopoietic stem cells that are harvested from a cancer patient, with the goal of creating a population of antigen-specific killer T cells that can target and kill tumors. Gaining access to this cutting-edge TCR identification technology has the potential to advance ImmunoCellular’s Stem-to-T-cell program and accelerate the Company’s ability to develop preclinical therapeutic candidates.
Launching new projects, products and services
Avrobio
Avrobio (MA, US; www.avrobio.com) has announced its launch plans. The company’s priority is to accelerate development of two novel cell and gene therapies. Phase 1 programs will be in the clinic by early to mid-2016 in both acute myeloid leukemia and Fabry disease. The company will simultaneously work to expand its proprietary cell and gene therapy platform to treat additional indications. AVR01 is designed to be an anticancer immunotherapy which triggers the immune system to first detect, and then eradicate, tumor cells. The patient’s cancer cells are genetically modified to express cytokine IL12. The modified cells are then infused back into the patient via a onetime procedure, where they activate cytotoxic CD4+ T cells which specifically target tumor cells and thus fight the cancer. A long-lasting anticancer immune response is maintained via both CD4+ and CD8+ cytotoxic T cells. AVR02 is designed to deliver lasting benefits for Fabry disease patients. The company’s approach is to genetically modify a patient’s own cells by adding a functional copy of the faulty gene. CD34+ hematopoetic stem cells are genetically modified to express the enzyme a-galactosidase A. The modified cells are then infused back into the patient via a one-time procedure. The objective is to deliver long-lasting or permanent, continuous elevation of endogenous enzyme thereby improving patient outcomes and reducing onerous lifetime biweekly intravenous infusions of enzyme replacement therapy.
Chimeric Therapeutics
The Cell Therapy Catapult (UK; www.ct.catapult.org.uk), the University of Birmingham (UK; www.birmingham.ac.uk), and Cancer Research Technology (UK; www.cancertechnology.co.uk), the commercialization arm of Cancer Research UK, launched a new company, Chimeric Therapeutics. The project is based on directing the CART cell towards a new, highly specific marker of tumor angiogenesis, CLEC14a. This therapy will act as a vasculature disruptive agent compromising oxygen supply to the tumors and inhibiting tumor growth. The technology is currently undergoing the final stages of preclinical development, and is planned to enter into clinical trials soon after.
Creative Medical Health and Angiostem
Creative Medical Health (AZ, US; www.creativemedicalhealth.com) formed a subsidiary company AngioStem dedicated to commercialization of its cardiovascular assets.
GE Healthcare, FedDev Ontario and Centre for Commercialization of Regenerative Medicine
GE Healthcare (UK; www.gehealthcare.com), the Federal Economic Development Agency for Southern Ontario (ON, Canada; www.feddevontario.gc.ca), and the Centre for Commercialization of Regenerative Medicine (CCRM; ON, Canada; www.ccrm.ca) are building a center for advanced therapeutic cell technologies in Toronto with an investment of CA$ 40million from GE and Federal Economic Development Agency. The center is being established to accelerate the development and adoption of cell manufacturing technologies that improve patient access to novel regenerative medicine-based therapies. CCRM and GE will welcome partners from pharma, biotech and cell therapy companies to bring this initiative to life.
Mesoblast and JCR Pharmaceuticals
Mesoblast (Australia; www.mesoblast.com) announced that its licensee in Japan, JCR Pharmaceuticals (Japan, www.jcrpharm.co.jp/en), launched its mesenchymal stem cell product TEMCELL® HS for the treatment of acute graft versus host disease (aGVHD) in children and adults in Japan. TEMCELL is the first allogeneic cell therapy to be fully approved in Japan. The Japanese Government’s National Health Insurance set reimbursement for TEMCELL at ¥868,680 (approximately US$ 7,700) per bag of 72 million cells. In Japan, the average adult patient is expected to receive at least 16 or up to 24 bags of 72 million cells. On this basis, Mesoblast expects a treatment course of TEMCELL in an adult Japanese patient to be reimbursed at a minimum of ¥13,898,880 (approximately US$ 123,000) or up to ¥20,848,320 (approximately US$ 185,000). Under its agreement with JCR, Mesoblast is entitled to receive royalties and other payments at predefined thresholds of cumulative net sales. In the world’s largest healthcare market, the United States, there are currently no approved therapies for patients with acute steroid-refractory GVHD, and off-label options have demonstrated mixed efficacy with high toxicity. To support filing of a biologic license application (BLA) to the United States Food and Drug Administration for regulatory approval, Mesoblast is conducting a 60-patient, open label Phase 3 trial using MSC-100-IV as front-line therapy in children with steroid-refractory aGVHD. After filing a BLA for pediatric approval of MSC-100-IV, Mesoblast plans to conduct a further trial to support a product approval of its cell therapy in adults with gastrointestinal or liver aGVHD, the patient groups who have the highest mortality risk. In the United States, pricing reimbursement methodology is expected to consider the burden of illness associated with steroid-refractory aGVHD as well as health utilization costs, and may result in a higher price than in Japan.
National Immunotherapy Coalition
Leaders from large pharma including Celgene (NJ, USA; www.celgene.com) and Amgen (CA, USA; www.amgen.com), biotech including NantWorks (CA, USA; www.nantworks.com), NantKwest (CA, USA; www.nantkwest.com), Etubics (WA, USA; www.etubics.com), Altor Bioscience (FL, USA; www.altorbioscience.com), and Precision Biologics (TX, USA; www.precision-biologics.com), major academic cancer centers and community oncologists announced the launch of The National Immunotherapy Coalition (NIC; www.cancermoonshot2020.org), a historic alliance – in collaboration with Independence Blue Cross (PA, USA; www.ibx.com) – with a singular focus: accelerating the potential of combination immunotherapies as the next generation standard of care in patients with cancer. This unprecedented collaboration of multinational pharmaceutical, biotechnology companies, academic centers and community oncologists will make possible access to over 60 novel and approved agents under exploration in the war against cancer and will enable rapid testing of novel immunotherapy combination protocols, forming the basis of The Cancer MoonShot 2020. The NIC will design, initiate and complete randomized clinical trials in cancer patients with cancer at all stages of disease in up to 20 tumor types in as many as 20,000 patients by the year 2020.
Oxford BioMedica
Oxford BioMedica (UK; www.oxfordbiomedica.co.uk) has initiated work on a second CART program for an undisclosed indication. Under an agreement signed with Novartis (Switzerland; www.novartis.com) in October 2014, Oxford BioMedica will undertake process development and manufacturing for the lentiviral vector associated with the new program. Oxford BioMedica is currently manufacturing lentiviral vector expressing CTL019 for Novartis and carrying out process development work to establish the next-generation manufacturing process. CTL019, formerly known as CART-19 are CART directed against CD19. The Group also granted Novartis a nonexclusive license in oncology under the Group’s LentiVector® platform and an exclusive license for the worldwide development and commercialization of all CART cell products arising from the process development collaboration. In return, Oxford BioMedica will receive undisclosed royalties on potential future sales of CART products covered by the agreement.
TxCell
TxCell SA (France; www.txcell.com) has launched new process industrialization laboratories and technology transfer academy facilities in Sophia Antipolis, France. These new facilities will be primarily dedicated to the improvement of the existing TxCell manufacturing process for its ASTrIA and ENTrIA platforms.
Achievements
Emulate
Emulate (MA, USA; www.emulatebio.com) opened its new headquarters and laboratories in Boston. The new facility will be a workplace for the company’s 40 employees, with plans for expansion to 85 employees within the coming year. Coming just 18 months after Emulate’s launch, the opening and scale-up of this new 1800 m2 expanded headquarters provides laboratories and facilities to support commercial activities, product development, and collaborative research programs for the Organs-on-Chips technology.
Minerva
Minerva Biotechnologies (MA, US; www.minervabio.com) reported a simple method of inducing naïve state pluripotency in human stem cells with a recombinant, truncated form of the human NME7 protein [1]. NME7 protein quickly and easily induces a stable naïve state in human stem cells without the need for inhibitors, transgenes, feeder cells, or any other growth factor.
Osiris
Osiris Therapeutics (MD, US; www.osiris.com) announced that the Medicare contractor, Cahaba Government Benefit Administrators (AL, US; www.cahabagba.com), has confirmed that Grafix, a cryopreserved placental membrane, has been approved for coverage for patients with chronic wounds. Coverage for Grafix from Cahaba became effective January 1, 2016. This Medicare Administrative Contractor covers the states of Alabama, Georgia and Tennessee, or approximately 3.8 million lives. In total, Grafix is now available to 90% of Medicare beneficiaries. In addition, Grafix has been awarded a contract with a major Group Purchasing Organization. Group Purchasing Organizations and Integrated Delivery Networks supply valuable financial and efficiency related services to healthcare providers, including major hospital networks in the US.
References
[1] Carter MG, Smagghe BJ, Stewart AK, Rapley JA, Lynch E, Bernier KJ, Keating KW, Hatziioannou VM, Hartman EJ, Bamdad CC. A Primitive Growth Factor, NME7AB , Is Sufficient to Induce Stable Naïve State Human Pluripotency; Reprogramming in This Novel Growth Factor Confers Superior Differentiation. Stem Cells. 2016 Jan 7 [Epub]