Industry Update: Business Development

Latest business developments compiled from 1—30 June 2015

Latest developments in the field of stem cell research and regenerative
medicine compiled from publicly available information and press releases
from non-academic institutions 1—30 June 2015, scheduled
to be published in Volume 10 Issue 7 of Regenerative Medicine.

Collaborations, partnerships & alliances

Co-development agreement: Amarna and CBmed

Amarna Therapeutics (the Netherlands; www.amarnatherapeutics.com) has entered into a cooperation with CBmed (Austria; www.cbmed.org) for the development of immunotherapies against acute lymphoblastic leukemia, obesity, diabetes mellitus type 2 and atherosclerotic cardiovascular disease. The agreement includes the design, development and testing in two separate projects of a chimeric antigen receptor (CAR) T cell therapy and reverse vaccines for the treatment of these major diseases with high unmet clinical needs. Amarna will contribute its proprietary SVac viral gene delivery vector platform to this collaboration and CBmed will perform in vitro and in vivo preclinical R&D and develop immunological assays in its core laboratory.

Co-development agreement: bluebird and Celgene

bluebird bio (MA, USA; www.bluebirdbio.com) and Celgene (NJ, USA; www.celgene.com) have amended their existing collaboration initiated in 2013 and restated to focus on developing product candidates targeting B-cell maturation antigen (BCMA) during a three-year collaboration term. BCMA is a cell surface protein that is expressed in normal plasma cells and in most multiple myeloma cells, but is absent from other normal tissues. They will work collaboratively on the initial, lead anti-BCMA product candidate (bb2121), with a Phase 1 clinical trial expected to begin enrollment in early 2016, and develop next-generation anti-BCMA product candidates. bluebird bio retains sole rights to develop all other CAR T cell programs developed by bluebird bio under the collaboration, including ongoing undisclosed preclinical programs with opportunities in both solid tumors and hematologic malignancies. Under the terms of the amended and restated collaboration agreement:

• bluebird bio will receive a US$ 25 million payment to develop the lead anti-BCMA product candidate through a Phase 1 clinical trial and develop next-generation anti-BCMA product candidates.
• bluebird bio will be responsible for the development of all anti-BCMA product candidates through the completion of Phase 1 studies.
• Additionally, on a product-by-product basis within the anti-BCMA product program, Celgene has an option to develop and commercialize each product candidate worldwide, and bluebird bio has the option to share equally in the development, promotion and profits of each product candidate in the USA. In addition to the payments described above and consistent with the prior agreement, Celgene would also pay bluebird bio specified development and regulatory milestone payments as well as royalty payments on net sales.

Co-development agreement: Horizon and DefiniGEN

Horizon Discovery Group (UK; www.horizondiscovery.com) and DefiniGEN (UK; www.definigen.com) will collaborate to develop a range of unique, gene-engineered induce pluripotent stem (iPSC) cell lines for use in research. Under the terms of the agreement, Horizon will perform genome engineering on the iPSC, which will then be differentiated by DefiniGEN. The project will initially focus on generation of ten iPSC lines for research in areas that currently lack high quality disease models. The resulting cell lines will be cultured, differentiated and quality controlled by DefiniGEN to ensure that scientists receive uniform cell populations suited to their experiments, alongside an isogenic control. The cell line reagents will be available through DefiniGEN and co-marketed by Horizon.

Collaboration agreement: CellResearch, University of Colorado and ClinImmune

CellResearch Corporation (CRC; Singapore; www.cellresearchcorp.com) has entered into a Services and Research Collaboration Agreement with the University of Colorado School Of Medicine (CO, USA; www.ucdenver.edu) and ClinImmune Labs (CO USA; www.clinimmune.com), which have a US FDA licensed current Good Manufacturing Practice (cGMP) stem cell/cord blood bank. The agreement has the objective of achieving US FDA approval for therapeutic products of umbilical cord lining membrane progenitor/stem cells. This first collaboration will focus on the development of CRC’s proprietary and patented cord lining mesenchymal stem cells (MSC) for the treatment of diabetic wounds. Under the agreement, USA partners will initially provide technical and clinical guidance for the production and testing of a cell bank of CRC’s MSC. This will include the necessary preclinical and clinical testing needed by the US FDA for Clinical Phase I and II approval for the treatment of diabetic wounds.

Collaboration agreement: Benitec and ReNeuron

Benitec (Australia; www.benitec.com) has launched collaboration with ReNeuron (UK; www.reneuron.com) on cellular therapies with combined ddrnai and exosome program. Benitec and ReNeuron have completed a series of in vitro experiments that demonstrate that stem cells transduced with ddRNA-expression constructs produce exosomes that are effective at delivering expressed shRNAs to target (cancer) cells and to knock down a specific gene in those cells. The data also indicated that ReNeuron’s stem cells could be more effective than MSC for this purpose. Whilst preliminary, these results could open the potential for both companies’ platform technologies to be extended into a wide range of new therapeutic applications.

Collaboration agreement: Emulate and Janssen

Emulate (MA, USA; www.emulatebio.com) formed a research collaboration with Janssen Biotech (PA, USA; www.janssenbiotech.com) to deploy Emulate’s Organs-on-Chips platform across certain Janssen programs to better predict the potential human response of drug candidates and improve the drug development process.

The collaboration, which was facilitated by the Johnson & Johnson Innovation Center in (MA, USA; www.jnjinnovation.com), utilizes Emulate’s Organs-on-Chips to advance the clinical goals for three Janssen R&D programs at the stages of drug candidate design and selection. Emulate’s technology will also support Janssen’s effort to enhance drug discovery and development with its 3Rs program: reduction, refinement and replacement of animal testing. The public disclosure of this collaboration coincides with the achievement by Emulate and Janssen scientists of the first functional demonstration of Emulate’s Thrombosis-on-Chip platform. Using the new Thrombosis-on-Chip that models human response in an engineered living microenvironment, the Emulate and Janssen research teams are evaluating the potential for drug candidates to cause thrombosis, a potential side effect of certain drug classes such as immunotherapeutics and oncology drugs.

Collaboration agreement: Kite and bluebird

Kite Pharma (CA, USA; www.kitepharma.com) and bluebird bio (MA, USA; www.bluebirdbio.com) have entered into a collaboration agreement to co-develop and co-commercialize second generation T cell receptor (TCR) product candidates directed against the human papillomavirus type 16 E6 (HPV-16 E6) oncoprotein incorporating gene editing and lentiviral technologies. bluebird bio has a platform comprised of lentiviral gene delivery and gene editing capabilities, with a focus on rare diseases and cancer immunotherapies. Kite has a broad existing pipeline of TCR product candidates and will continue to develop its existing and wholly owned TCR programs directed against high-risk HPV. Under the terms of the agreement, both companies will jointly develop and commercialize second generation TCR product candidates directed against the HPV-16 E6 oncoprotein, incorporating gene editing to efficiently modify certain genes to enhance T cell function. In addition, the companies will explore using lentiviral vectors to optimize delivery of HPV-16 E6 TCRs into patient T cells. Kite will lead the program in the U.S., and bluebird bio will have the option to lead the program in the European Union. Both companies will share overall costs, including research and development and sales and marketing expenses, and profits will be equally split between the companies. Additionally, Kite will have a co-promotion option in the European Union, and bluebird will have a co-promotion option in the USA.

Licensing agreement: Atara and MSK

Atara Biotherapeutics (CA, USA; www.atarabio.com) has exercised its exclusive option with Memorial Sloan Kettering Cancer Center (MSK; NY, USA; www.mskcc.org) to license certain clinical stage, allogeneic T-cell therapies for the treatment of cancers and persistent viral infections. In connection with the exercise of the option, the Atara license agreement with MSK grants Atara exclusive worldwide rights to the following three allogeneic T-cell therapies:

• T-cells activated against Epstein Barr Virus, or EBV (Phase 2);
• T-cells activated against Cytomegalovirus, or CMV (Phase 2); and
• T-cells activated against Wilms Tumor 1, or WT1 (Phase 1)

These three programs share a common technology, under which third-party donor-derived whole blood is collected and enriched for T lymphocytes, or T-cells. The T-cells are then exposed to certain antigens, and the resulting activated T-cells are characterized and stored for future therapeutic use. Using a proprietary algorithm, patients are treated with a partially human leukocyte antigen, or HLA, matched cell line, providing an “off-the-shelf,” allogeneic, cellular therapeutic option for patients. These T-cell products are intended to work by targeting the abnormal cells expressing the applicable target antigen and killing them.

Launching new projects, products and services

Alllele

Allele Biotechnology & Pharmaceuticals (CA, USA; www.allelebiotech.com) has purchased a new facility intended for its cGMP production of clinical-grade cells for cell therapy applications. The 1672 m² (8,000 square-foot) facility, located near the main headquarters of Allele in San Diego, California, will be the center of production of human iPSC lines using Allele’s proprietary synthetic mRNA platform.

Cord Blood Registry

Cord Blood Registry (CA, USA; www.cordblood.com) launched a registry designed to offer insight into common diseases and conditions affecting families and to bring patients, healthcare professionals and researchers together to expedite and facilitate research related to the discovery of stem cell treatments and potential cures. The registry serves as an extension to Newborn Possibilities Program®, which uses health history screening to identify families who may benefit from cord blood banking and offers free newborn stem cell processing and storage for five years to families with a qualifying medical need.

STEMCELL Technologies

STEMCELL Technologies (BC, Canada; www.stemcell.com) launch of ImmunoCultâ„¢ Human T Cell Activator reagents and ImmunoCultâ„¢-XF T Cell Expansion Medium to support T cell researchers in their goal to develop CAR T cell immunotherapeutics. ImmunoCultâ„¢ Human T Cell Activators are soluble reagents that elicit robust activation and expansion of T cells and are highly shelf stable. The Activator reagents are optimized for use with the xeno- and serum-free ImmunoCultâ„¢-XF T Cell Expansion Medium. Together, ImmunoCultâ„¢ T Cell Activator reagents and ImmunoCultâ„¢-XF T Cell Expansion Medium promote a streamlined workflow for the ex vivo activation and expansion of human T cells.

Stemgent

Stemgent (MA, USA; www.stemgent.com), a ReproCELL Group Company (Japan; www.reprocell.com/en/) has launched its new StemRNAâ„¢-SR Reprogramming Kit, the first commercially available RNA reprogramming kit applicable to cellular reprogramming of a blood-derived cell type. This non-viral, non-DNA reprogramming kit combines self-replicative RNA (srRNA) and microRNA technology, providing stem cell researchers with a safe, flexible and cost-effective cellular reprogramming method applicable to both human fibroblasts and blood-derived endothelial progenitor cells, which can be efficiently established from fresh or cryopreserved human peripheral and cord blood.

Thermo Fisher

Thermo Fisher Scientific (MA, USA; www.thermofisher.com) launched The Gibco Essential 8 Flex Medium, a new pluripotent stem cell medium designed to offer researchers schedule flexibility, allowing two-day breaks from culture feeding without having to make changes to current workflows or compromise culture quality. Researchers can save time and reduce sample handling, thereby decreasing the risk of contamination. The Gibco Essential 8 Flex Media is for research use only and is part of the Gibco Essential 8 Medium family of products launched in partnership with Cellular Dynamics International (WI, USA; www.cellulardynamics.com), a FUJIFILM company (Japan; www.fujifilm.com).

Achievements

Emulate

Emulate (MA, USA; www.emulatebio.com) announced that the company’s Human Organs-on-Chips have been named as overall winner of the ‘Design of the Year’ award by London’s Design Museum. The award is selected by design experts, practitioners, curators and academics from around the world, who were united in their responsibility to select a winner that emphasizes design’s impact on our lives now and in the future, solving diverse problems with innovation and intelligence.

STEMCELL Technologies

BIOTECanada (ON, Canada, www.biotech.ca), Canada’s national biotechnology industry association, has presented STEMCELL Technologies (BC, Canada; www.stemcell.com) with the Biotech Company of the Year award at this year’s BIO International Convention in Philadelphia. BIOTECanada hosts its annual Gold Leaf Awards in recognition of leaders and innovators in the life science community.