Industry Update: Business Development

Latest business developments compiled from August 1— September 30 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 August 1— September 30 2015, scheduled to be published in Volume 11 Issue 1 of Regenerative Medicine.

Collaborations, partnerships & alliances

Co-development agreement: Sanofi and Evotec

Sanofi (France; http://en.sanofi.com/) and Evotec (Germany; www.evotec.com) have announced plans to work together on the development of new therapies that might reduce or eliminate the need for diabetes patients to have insulin injections. The companies, which are already closely interlinked, are embarking on a project to develop new approaches based on the modulation of beta cells, the function of which is affected in both diabetes type I and II. A key goal of the alliance is a beta cell replacement therapy based human stem cells, and the partners also plan on using beta cells for high-throughput drug screening to identify novel small molecule or biologic approaches. Under the deal, Evotec is entitled to receive development, regulatory and commercial milestone payments, which could total more than 300 million Euros, as well as royalties on net sales of any products that make it to market. Earlier this year the firms announced a 250 million-Euro strategic alliance under which Evotec gained Sanofiʼs troubled operations in Toulouse, France, and agreed to provide a broad range of long-term drug discovery services.

Collaboration and distribution agreement: Celyad and Medisun

Celyad SA (Belgium; www.celyad.com) has entered into a new collaboration and distribution agreement with its Hong-Kong based partner, Medisun International Limited (website unavailable). This license agreement confirms Celyad’s intention to expand the global footprint of its lead cardiac disease cell therapy candidate for the treatment of ischemic heart failure, C-Cure®. Under the terms of the new license agreement, Celyad will conduct all clinical development and undertake any regulatory steps necessary for market approval in China, Hong-Kong, Taiwan and Macau. With a minimum of US$ 22.4 (€20) million, these activities will be funded by Medisun. Celyad expects initial clinical development activities to take place in Hong-Kong with the potential addition of clinical sites in Celyad’s CHART-2 trial, which is expected to be initiated before the end of 2015. In exchange for the license, and in addition to the benefit of the funding provided by Medisun to support clinical development, Celyad will receive royalties and profit sharing. The royalty rates ranging from 10% to 30% are calculated on total revenues of C-Cure, and profit sharing ranging from 20 to 25% are calculated on total revenues less royalties.

Development and licensing agreement: Heraeus and OrthoCyte

Heraeus Medical (Germany, http://heraeus-medical.com/en/home_15.html) and OrthoCyte (CA, USA; http://orthocyte.com), subsidiary of BioTime (CA, USA; www.biotimeinc.com), have entered into exclusive development and worldwide licensing agreements for the development of innovative bone grafting therapies based on the use of BioTime’s proprietary PureStem® human embryonic progenitor cell technology. Under the terms of the development agreement, Heraeus Medical would make an initial US$ 1 million upfront payment to OrthoCyte, and additional payments upon OrthoCyte’s attainment of certain product development milestones, and Heraeus will fund all ongoing product development activities through Investigational New Drug (IND) submission. Heraeus Medical, with its global marketing capability, will be responsible for worldwide sales if a product is successfully developed, can be demonstrated through clinical trials to be safe and effective, and receives regulatory approval for marketing. OrthoCyte will be responsible for product development and initially for manufacturing. Pursuant to the terms of the license agreement, OrthoCyte has licensed certain technology to Heraeus, and Heraeus has licensed certain technology to OrthoCyte. The license grant by OrthoCyte to Heraeus is exclusive and worldwide in the field of bone grafting for all osteoskeleton diseases and injuries, except oral maxillofacial. The license grant by Heraeus to OrthoCyte is exclusive and worldwide in all other fields. Pursuant to the license agreement, each of Heraeus and OrthoCyte will pay certain specified royalties to each other based on their respective net sales of the product developed under the development agreement.

Licensing agreement: DefiniGEN and University of Cambridge

DefiniGEN (UK; www.definigen.com) has strengthened its IP portfolio with a license for cutting edge lung stem cell technology from the University of Cambridge (www.cam.ac.uk). The technology will be used by DefiniGEN to develop new, optimized cell products and services for drug discovery and the study of lung diseases, including cystic fibrosis. The technology licensed by DefiniGEN uses induced pluripotent stem cells (iPSC) to recreate embryonic lung development in the lab by activating a process known as gastrulation, in which the cells form distinct layers, from which the lung ‘grows’. Uniquely, the technology enables these cells to develop further, into distal airway tissue. The distal airway is the part of the lung responsible for gas exchange and is often implicated in disease, such as cystic fibrosis, some forms of lung cancer and emphysema.

Licensing agreement: Minerva and ID Pharma

Minerva Biotechnologies (MA, USA; www.minervabio.com) and ID Pharma (formerly DNAVEC; Japan; www.DNAVEC.co.jp/en/index.html) have signed an agreement granting Minerva worldwide rights to use and commercialize ID Pharma’s non-integrating Sendai virus vectors, together with Minerva’s proprietary technology, for generating iPSC.

Licensing agreement: Minerva and iPS Academia Japan

Minerva Biotechnologies (MA, USA; www.minervabio.com) and iPS Academia Japan (Japan, http://ips-cell.net/e/) have signed an agreement granting Minerva worldwide rights to use and commercialize the iPSC patent portfolio. Minerva Biotechnologies discovered a naturally occurring, primitive growth factor that continues this reprogramming to an even earlier, embryonic-like point called the ‘naïve’ state. Naïve stem cells have several advantages over currently available stem cells (known as ‘primed’ state). These advantages are important for the future of stem cell therapies. Naïve stem cells do not yet have DNA methylation marks that commit the cells to certain developmental decisions. Additionally, naïve stem cells have a much higher cloning efficiency than primed state cells, which is critical for the realization of stem cell based gene therapies. Importantly, only naïve stem cells can contribute to the generation of chimeric animals.

Licensing agreement: STEMCELL Technologies and iPS Academia Japan

STEMCELL Technologies (BC, Canada; www.stemcell.com) has signed a patent license agreement with iPS Academia Japan (Japan, http://ips-cell.net/e/) to license and commercialize iPS Academia Japan’s patented technologies for iPSC research. This agreement will enable STEMCELL Technologies to develop, manufacture, and distribute products that are optimized for cellular reprogramming. This further expands STEMCELL’s extensive portfolio of products for human pluripotent stem cell research research, which includes ReproTeSRâ„¢ and TeSRâ„¢-E7â„¢ media for reprogramming, the TeSRâ„¢ family of maintenance media, and the STEMdiffâ„¢ product line for robust and reliable differentiation to various cell lineages.

Marketing agreement: CDI and SeouLin

Cellular Dynamics International (WI, USA; http://cellulardynamics.com), a FUJIFILM company (Japan; www.fujifilmholdings.com/en/index.html) had entered into an exclusive agreement with SeouLin Bioscience (Korea; www.seoulin.co.kr/eng/), for the distribution of Cellular Dynamics’ products in the Republic of Korea. As part of the agreement, SeouLin Bioscience will handle first-level technical support inquiries from its customers. Financial terms were not disclosed.

Partnership agreement: Avita and University of Huddersfield

Avita Medical (Australia; www.avitamedical.com) has forged a partnership with the University of Huddersfield (UK; www.hud.ac.uk) to explore the mechanism of Regenerative Epithelial Suspension (RESâ„¢), which is being sprayed from Avita’s ReCell® device, to better understand its ability to effectively treat burns, hard-to-heal wounds and skin trauma. The objective of the research is to provide greater understanding of the cellular interactions present in RES and the roles these play in regenerating natural healthy skin. It is anticipated that the results of this research will help enable clinicians to make more informed patient selection leading to superior clinical outcomes.

Service agreement: Cytovance and NeuroFx

NeuroFx (IN, USA; www.neurofx.com) is teaming up with Cytovance Biologics (OK, USA; www.cytovance.com) to develop a therapeutic factor concentrate (TFC) manufacturing process. TFC, derived from adult adipose stem cells, is an off-the-shelf, ready-to-use product made from conditioned medium obtained from culturing paracrine factors-secreting mesenchymal stromal/stem cells (MSC).

Launching new projects, products and services

Catapult

The Cell Therapy Catapult (UK; https://ct.catapult.org.uk) has welcomed the decision by Stevenage Borough Council to grant planning permission to construct its US$ 83.3 (£55) million large-scale good manufacturing practices (GMP) center. The 7200 m² manufacturing centre, which is expected to open in 2017, will be managed by the Cell Therapy Catapult and will be used for manufacture of products for late phase clinical trials and commercial supply of advanced therapeutic medicinal products including cell and gene therapies. The facility is expected to create up to 150 jobs and its position on the Stevenage Bioscience Catalyst campus will provide additional inward investment from global companies, as well as support the SME biotech and life sciences companies based in the UK and will complement the existing UK capability.

Celprogen

Celprogen (CA, USA; www.celprogen.com) has developed a novel product FolliStemâ„¢ for regrowth of human hair. FolliStem is manufactured from Adipose Derived Stem Cells that also contains STEMC8007 the human hair follicle stem cell stimulator. FolliStem is applied topically once daily after washing the scalp prior to going to bed. The product has been tested in humans and has produced marked improvements within 40-45 days of application. FolliStem stimulates the growth of hair only if the hair follicle is present or is in a dormant / arrested growth stage.

CIRM & Coriell

The largest publicly available stem cell bank in the world is open for business in September 2015, offering the first 300 different stem cell lines for researchers interested in gaining a deeper understanding of, and developing treatments for 11 common diseases and disorders. The Bank, which is funded by the California Institute for Regenerative Medicine (CIRM; CA, USA: www.cirm.ca.gov) is collecting tissue samples from up to 3,000 volunteer donors. Some of the tissue collected will be from people with a particular condition, others will be from healthy individuals and will act as a control, allowing us to compare how healthy cells are different from disease-affected cells. The conditions that are the focus of the iPSC Bank are:

• Heart disease
• Lung disease
• Liver disease
• Blinding eye diseases
• Childhood neurological disorders such as epilepsy, autism and cerebral palsy
• Alzheimer’s Disease

Tissue samples are being collected by researchers at the University of California San Francisco, San Diego, Los Angeles and Stanford University. All donors undergo a rigorous consent and approval process before any tissue is collected. Once collected those samples are then turned into different iPSC lines by Cellular Dynamics International (WI, USA; http://cellulardynamics.com), a FUJIFILM company (Japan; www.fujifilmholdings.com/en/index.html), and then stored and distributed by Coriell Institute for Medical Research (NJ, USA; www.coriell.org) from a facility at the Buck Institute in Novato, California.

ESI BIO

ESI BIO (CA, USA; www.esibio.com), the stem cell products division of BioTime (CA, USA; www.biotimeinc.com), has released a technology platform designed to give researchers new standardized in vitro assays with greater physiological relevance and accuracy. The VascuNetâ„¢ Pericyte Co-Culture Assay provides a stable, clinically relevant angiogenesis model not currently obtainable with other vascular network systems. VascuNet Pericyte Co-Culture Assay is a novel angiogenesis model that, with the inclusion of both endothelial cells and pericytes, provides a more clinically relevant research platform. Cellular networks in this co-culture system can easily be maintained for extended periods of time in vitro, allowing for a more complete and accurate model to study the effects of drugs and therapeutic compounds on vascular network formation. This breakthrough technology in angiogenesis assays was developed in collaboration with ReCyte Therapeutics (CA, USA; www.recyte.com), another BioTime subsidiary, toward the goal of providing clinically relevant research platforms to the greater pharmaceutical drug screening and research community.

FUJIFILM

FUJIFILM (Japan; www.fujifilmholdings.com/en/index.html) has announced that it will establish Cellular Dynamics International Japan, a company for developing, manufacturing and marketing differentiated cells derived from iPSC for building IPSC business to support drug discovery in Japan. Cellular Dynamics International Japan will initially import IPSC cell-derived differentiated cells designed for drug discovery support, manufactured by the US-based FUJIFILM Group company, Cellular Dynamics International (WI, USA; http://cellulardynamics.com), and market them to universities, research institutes and private enterprises in Japan.

Immatics US

Immatics Biotechnologies (Germany; http://immatics.com) and The University of Texas MD Anderson Cancer Center (TX, USA; www.mdanderson.org) have launched Immatics US, a new company aiming at becoming a global leader in adoptive cellular therapies for the treatment of a range of tumor types. Immatics US will develop both autologous and allogenic adoptive cellular therapy approaches by capitalizing on MD Anderson’s world-leading clinical oncology and cell therapy expertise and Immatics’ unrivaled cancer target, and T-cell receptor (TCR) discovery capabilities. Immatics US, Inc. will be based in Houston and has secured a first funding round totaling over US$ 60 million with more than US$ 40 million committed by the parent company Immatics Biotechnologies and $19.7 million by a recently awarded grant from the Cancer Prevention and Research Institute of Texas (CPRIT). MD Anderson is a shareholder in Immatics US. Immatics has been able to use its unique and world-leading technology platform XPRESIDENT® for the discovery and further qualification of dozens of novel, proprietary and highly specific cancer targets that can be used as the basis for a range of cancer immunotherapy applications including adoptive cellular therapy. This capability will enable the TCR-based approaches, developed by Immatics US, to have complementary utility with other approaches for addressing tumor targets.

Lonza

Lonza (Switzerland; www.lonza.com) has enhanced its range of Poieticsâ„¢ Human Bone Marrow-Derived MSCs by expanding the characterization of these cells to meet industry guidelines for translational and cell therapy research applications. In accordance with the 2006 International Society for Cellular Therapy criteria, Lonza’s MSCs are now tested to ensure the expression of CD90 and CD73, as well as confirming the absence of HLA-DR and CD19. The cells also express CD29, CD44, CD105 and CD166, and do not express CD14, CD34 or CD45. All cells are free from mycoplasma, bacteria, yeast and fungi, and all donors and/or cell lots test negative for HIV-1, hepatitis B and hepatitis C. In addition, a certificate of analysis is provided for each cell lot purchased.

Achievements

BioCision

BioCision (CA, USA; www.biocision.com) has received Instrument Business Outlook’s (IBO) Gold Award for its ThawSTARâ„¢ automated cell-thawing system. Candidates are chosen from new products that IBO monitors through trade shows, trade publications, press releases and the Internet. Award winners are selected solely based on their industrial design; criteria include innovation, aesthetics, functionality and utility for products that have begun shipping between August 2014 and July 2015. The winners demonstrate how industrial design can improve a product’s functionality and the end-user’s experience. According to IBO, the ThawSTAR cell thawing system was chosen for its novel approach to lab equipment design represented in its compact size, touchscreen-free intuitive interface and white finish that communicates simplicity.

Ocata

Ocata Therapeutics (MA, USA; www.ocata.com) reported that it has successfully used its proprietary hemangio-derived mesenchymal cell (HMCTM) technology to treat dogs with canine anal furunculosis (CAF), which shares many features with Crohn’s disease [1]. Canines have a physiology and sophisticated immune system that closely resembles that of humans, and canines are the only species that naturally develop symptoms and pathology similar to human fistulizing Crohn’s disease, including recurrent fistula activity, a difficult-to-treat manifestation of this chronic inflammatory bowel disorder. They treated six canines that were refractory to standard treatment, including cyclosporine therapy, and all of the canines were found to be completely free of fistulas at three months post-injection.

References

[1] Ferrer L, Kimbrel EA, Lam A et al. Treatment of perianal fistulas with human embryonic stem cell-derived MSCs: a canine model of human fistulizing Crohn’s disease. Regen. Med. 2015 Sep 21. [Epub ahead of print]