Industry Update: Business Development

Latest business developments compiled from 1—31 December, 2015

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 1—31 December 2015, scheduled to be published in Volume 11 Issue 3 of Regenerative Medicine.

Collaborations, partnerships & alliances

Co-development agreement: Fibrocell and Interexon

Takeda Pharmaceutical ( Japan; www.takeda.com) and Kyoto University’s Center for iPS Cell Research and Application (CiRA; Japan; www.cira.kyoto-u.ac.jp/e) have started joint research on the development of new drugs using induced pluripotent stem cells (iPSC). The joint research will cover six diseases – cancer, heart failure, diabetes mellitus, neurodegenerative disorders, intractable muscle diseases and amyotrophic lateral sclerosis. Takeda and CiRA plan to start clinical trials within three years at the earliest. The number of diseases covered by the joint research will be increased to 12. Takeda will provide US$170 million (¥20 billion) to cover research costs over 10 years.

Co-development and licensing agreement: Adaptimmune and Universal Cells

Adaptimmune Therapeutics (UK; www.adaptimmune.com) and Universal Cells (WA, US; www.universalcells.com) have entered into a collaboration and exclusive license agreement for the development of allogeneic T-cell therapies. With Universal Cells’ proprietary gene editing technology, Adaptimmune intends to develop universally applicable affinity enhanced donor T-cells. The enhanced T-cell technology involves selective engineering of cell surface proteins (T-cell receptor /TCRs/ and class I and class II HLA proteins), without the use of nucleases, to develop universal T-cell products. Adaptimmune and Universal Cells are planning to develop the off-the-shelf allogeneic affinity-enhanced T-cell therapeutics to treat large patient populations. Under the terms of the agreement, Universal Cells will grant to Adaptimmune an exclusive, sub-licensable, worldwide license to use, sell, supply, manufacture, import, and develop products and services utilizing Universal Cells’ technology within the T-cell immunotherapy field. Universal Cells will receive an upfront license and start-up fee of US$ 5.5 million, and will be eligible for up to US$ 41 million in milestone payments for certain development and product milestones.

Collaboration agreement: Emulate and Merck

Emulate Inc. (MA, USA; www.emulatebio.com) announced an expanded research collaboration with Merck (NY, USA; www.merck.com) to deploy Emulate’s Organ-Chips across certain Merck discovery programs to improve models of human inflammatory diseases and better predict the potential human response of therapeutic candidates. The research will focus on using Emulate’s Small Airway Lung-Chip and Intestine-Chip to enable predictive modeling of inflammatory processes in the human lung and the gastrointestinal system.Under the terms of the collaboration agreement, Emulate will retain the rights to any resulting discoveries related to the Organ-Chip technology. In addition, Merck has the option to extend the collaboration to include additional organs, disease models or drug programs. Other terms of the agreement are not disclosed.

Collaboration agreement: Kiadis and Thalassemia International Federation

Kiadis Pharma (Netherlands; www.kiadis.com) announced a collaboration with the Thalassaemia International Federation (TIF; Cyprus; www.thalassaemia.org.cy). With support of international thalassaemia experts through the network of the TIF, Kiadis Pharma aims to develop innovative products to improve treatment of thalassaemia patients and will be entering clinical development in the first quarter of 2016. Kiadis Pharma believes that its product Allodepleted T-cell ImmunotheRapeutics (ATIR201™) has the potential to address the current risks and limitations connected with hematopoietic stem cell transplantation (HSCT), being graft-versus-host-disease (GVHD), opportunistic infections and limited donor availability, and make HSCT a first-choice treatment of β-thalassaemia major. ATIR101™ provides for a safe donor lymphocyte infusion from a haploidentical family member without the risk of causing GVHD. The T-cells in ATIR101™ will help fight infections and remaining tumor cells and thereby bridge the time until the immune system has fully re-grown from stem cells in the transplanted graft. The collaboration will allow the TIF to further expand its international educational and awareness programs for patients and health-care professionals, with a specific focus on HSCT as a curative treatment for thalassaemia patients.

Collaboration agreement: Pluristem Therapeutics and Fukushima Medical University

Pluristem Therapeutics (Israel; www.pluristem.com) has signed a Memorandum of Understanding (MOU) for a collaboration with Fukushima Medical University (Japan; www.fmu.ac.jp/univ/en). The purpose of the collaboration is to develop Pluristem’s PLX-R18 cells for the treatment of Acute Radiation Syndrome (ARS), and for morbidities following radiotherapy in cancer patients. In this new collaboration PLX-R18 cells will be studied primarily as a potential treatment for radiation-induced damage to the skin, lungs and gastrointestinal tract. The parties intend to develop preclinical models of radiation damage in these tissues, and then use them in trials. Pluristem will contribute PLX-R18 cells and scientific knowledge, while Fukushima Medical University will conduct the studies, and provide the required resources. The collaboration will proceed alongside research supported by the U.S. National Institutes of Health (NIH), which is studying PLX-R18 as a potential treatment for the hematologic component of ARS.

Collaboration and development agreement: Roche and SQZ Biotech

Roche (Switzerland; www.roche.com) will partner with SQZ Biotech (MA, USA; www.sqzbiotech.com) to develop a cell therapy platform that would empower a patient’s own immune cells to fight a broad range of cancers. The proposed therapy involves applying SQZ’s “CellSqueeze” technology–which entails engineering B cells as an oncology therapeutic platform–in order to introduce tumor-associated proteins into a patient’s B-cells which will then help activate killer T-cells to attack the cancer. Cell squeeze technology is a microfluidic chip that enables the delivery of materials into almost any cell type, including primary human-derived cells. SQZ maintains the exclusive worldwide license from MIT for CellSqueeze for any application. Roche agreed to pay SQZ more than US$ 500 million in upfront and potential clinical, regulatory, and sales milestone-based payments for advancement of all products across all planned indications, in addition to royalties on potential future products.

Collaboration and licensing agreement: Nohla and Fred Hutchinson

Nohla Therapeutics Inc. (WA, USA; www.nohlatherapeutics.com) signed an exclusive licensing and collaboration agreement with the Fred Hutchinson Cancer Research Center (WA, USA; www.fredhutch.org). The transaction with the Fred Hutchinson provides Nohla with a 20 year worldwide exclusive licensing agreement to seven patent families and know-how relating to an ex vivo expanded umbilical cord blood platform. Two Investigational New Drugs (IND) were also transferred as part of the transaction. Patents under this agreement cover the use of a non-HLA matched expanded cord blood product, which has been used in a number of clinical trials already. In addition to the license agreement, Nohla has executed a five-year Collaboration Agreement with Fred Hutchinson, in the form of sponsored research agreement. The Collaboration Agreement will accelerate both pre-clinical and clinical research being conducted within labs at the Fred Hutchinson. The Collaboration commitment consists of USD $1.5 million per annum with initial capital directed toward manufacturing transfer

Launching new projects, products and services

Allcells

AllCells (CA, USA; www.allcells.com) announced its expansion into therapeutic applications through the introduction of clinical grade products for further processing of allogeneic cell therapies. AllCells is initially introducing standard and custom pack sizes of Clinical Grade Fresh Whole Bone Marrow early 2016, followed by Clinical Grade Fresh Leuko Pak products. These clinical grade products serve as a rich source of adult human stem cells such as CD34+ hematopoietic stem and progenitor cells (HSPCs) capable of differentiating into various mature blood cell types, and/or mesenchymal stem cells. During the past several months, the company has been developing compliance with USFDA 21 CFR regulations.

Boyalife

Boyalife Group (China; www.boyalife.com/english) and its partners are building the world’s biggest cloning plant in the northern Chinese port of Tianjin, where it is due to go into production within the next seven months and aims for an output of one million cloned cows a year by 2020. In the factory pipeline are also thoroughbred racehorses, as well as pet and police dogs. Boyalife is currently working with its South Korean partner Sooam Biotech Research Foundation (http://en.sooam.com/main.html) and the Chinese Academy of Sciences (http://english.cas.cn) to improve primate cloning capacity to create better test animals for disease research. The firm does not currently engage in human cloning activities because of a ‘possible adverse public reaction’.

Neurona

Neurona Therapeutics (CA, USA; www.neuronatherapeutics.com) has been launched with a US$ 23.5 million Series A financing led by the science-driven venture capital firm The Column Group (CA, USA; www.thecolumngroup.com). Neurona is focused on unique compositions of cells that can be precisely targeted, integrated into damaged neural circuits, and provide activity-dependent regulation. Neurona is founded by neuroscientists and stem cell scientists from the University of California, San Francisco (UCSF; www.ucsf.edu).

Orig3n

Orig3n (MA, USA; www.orig3n.com) is collecting blood samples from amateur athletes in order to create an IPSC library, which it will market to pharmaceutical and biotechnology companies in an effort to reduce their failure rates. Orig3n has recently raised US$ 3.1 million, which will contribute to development of a consumer iPSC storage service, named ‘Life Capsule’. This service allows consumers to store their iPSC for future potential cellular therapy application.

Achievements

Emulate

Emulate Inc. (MA, USA; www.emulatebio.com) has developed a new living human Lung-Chip system that accurately recreates the unique structure and function of the human lung small airways within micro-engineered [1]. The results demonstrate that the Small Airway Lung-Chip can model complex tissue functions of the lung within the micro-engineered chips to enable a human model of lung inflammatory disorders, specifically asthma and chronic pulmonary obstructive disease (COPD), and more effectively predict human response to anti-inflammatory drugs, compared to existing animal models.

Ocata

Ocata Therapeutics, Inc. (MA, USA; www.ocata.com) has published a method for generating scalable amounts of human embryonic stem cell (hESC)-derived corneal endothelial cells (CEC). Disease and injury to the cornea are leading causes of blindness worldwide. With Ocata’s two-step differentiation method for generating hESC-CECs, in-vitro, the future therapy may not rely only on donor corneas

In unrelated study, Ocata reported that its proprietary hemangio-derived mesenchymal cell technology can be used to prevent the progression of fatal lupus nephritis in NZB/W F1 mice, a spontaneous model for systemic lupus erythematosus [2]. The study shows that the cells prevented the progression of fatal lupus and significantly reduced proteinuria and serum creatinine and preserved renal architecture. The study also demonstrated scalability and efficacy in cell therapy for lupus.

References

[1]Benam KH, Villenave R, Lucchesi C et al. Small airway-on-a-chip enables analysis of human lung inflammation and drug responses in vitro. Nat Methods. 2015 Dec 21 [Epub ahead of print]

[2]McCabe KL, Kunzevitzky NJ, Chiswell BP, Xia X, Goldberg JL, Lanza R. Efficient Generation of Human Embryonic Stem Cell-Derived Corneal Endothelial Cells by Directed Differentiation. PLoS One 10 (12), e0145266 (2015).