Latest developments compiled from January 01 — February 28, 2017.
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 01 — February 28, 2017, scheduled to be published in Volume 12 Issue 4 of Regenerative Medicine.
Collaborations, partnerships & alliances
Co-development agreement: Locate and Heraeus
Locate Therapeutics (UK; www.locatetherapeutics.com) has announced the deepening of a development collaboration with the Heraeus Medical (Germany; www.heraeus.com). The new deal focuses on the use of Locate’s “state of the art” Targeted, Orchestrated Signaling, TAOS®, scaffold technology, in new areas of orthopedic application. TAOS’ injectable particulate formulation is thermally-triggered to solidify into a space-filling open porous depot that supports tissue repair before degrading away.
Co-development agreement: Promethera and LifeLiver
Promethera Biosciences (Belgium; www.promethera.com) and LifeLiver (Korea) have announced a strategic alliance to jointly develop Promethera’s suite of cell-based liver disease therapies in South Korea. This alliance initially includes: 1) a license agreement for HepaStem and H2Stem to develop and commercialize these platforms in nonalcoholic steatohepatitis and acute-on-chronic liver failure in Korea, and 2) a supply agreement to provide Heparesc® for LifeLiver’s proprietary bioartificial liver system. LifeLiver will combine Promethera’s human mature hepatocytes liver cell suspension, Heparesc®, with its proprietary bioartificial liver system for the ex vivo treatment of patients with severe liver diseases such as acute liver failure. The therapeutic goal of this approach would be to “humanize” the bioartificial liver bioreactor and to boost supply of hepatocytes. Future directions of this strategic alliance will involve other indications currently clinically investigated by Promethera such as urea cycle disorders and will include the HepaStem and H2Stem technologies.
Co-development agreement: ZIOPHARM and Interexon
ZIOPHARM Oncology (MA, USA; www.ziopharm.com) and Intrexon (MD, USA; www.dna.com) have announced the signing of a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI) for the development of adoptive cell transfer-based immunotherapies genetically modified using the Sleeping Beauty transposon/transposase system to express T-cell receptors (TCRs) for the treatment of solid tumors. The principal goal of the CRADA is to develop and evaluate ACT for patients with advanced cancers using autologous peripheral blood lymphocytes genetically modified using the non-viral Sleeping Beauty system to express TCRs that recognize specific immunogenic mutations, or neoantigens, expressed within a patient’s cancer. Clinical evaluations of the ability of these Sleeping Beauty -engineered peripheral blood lymphocytes will be also performed.
Co-development and commercialization agreement: Cynata and FujiFilm
Cynata Therapeutics (Australia; www.cynata.com), stem cell and regenerative medicine company that is developing a therapeutic stem cell platform technology, Cymerusâ„¢, originating from the University of Wisconsin (WI, USA; www.wisc.edu), has executed a license option agreement with FUJIFILM (Japan; www.fujifilm.com) for the development and commercialization of Cynata technology, including induced pluripotent stem cell (iPSC)-derived therapeutic mesenchymal stem cell (MSC) product, CYP-001. After the transaction is finalized, FUJIFILM would emerge with a 10.01% stake in Cynata. Under this agreement, FUJIFILM has an option to an exclusive, worldwide license to market and sell CYP-001 in the field of prevention and treatment of graft-versus-host disease (GvHD). This option is exercisable at any time up to 90 days after the completion of the primary evaluation period of Cynata’s current phase I clinical trial in GvHD. An upfront fee of US$ 3 million is payable, which, together with other potential future milestones, totals over US$ 45.6 (A$ 60) million in potential one-time payments, along with double-digit royalties on net sales of CYP-001 product. Should FUJIFILM choose to exercise this option, future CYP-001 development costs will be borne by FUJIFILM.
Co-development and commercialization agreement: Efferent and Evotec
Efferent Labs (NY, USA; www.efferentlabs.com) has entered into a multi-year agreement with Evotec (Germany; www.evotec.com) for the continued development of Efferent’s CytoCommâ„¢ Living Biosensor System. Under the agreement, Efferent will work with Evotec to further develop and validate the CytoComm Living Biosensor System. The development will focus on the optimization and validation of targeted pathways, leveraging Evotec’s state-of-the-art capability platforms and its expertise in cell biology, pathway modeling, and in vivo pharmacology. The agreement will continue through the commercialization of the CytoComm Living Biosensor System. The biosensor is injected just below the skin of the animal or patient and uses living cells to measure levels of molecules such as biomarkers, proteins and medications in the cells. It transmits data wirelessly to the cloud for analysis
Collaboration agreement: Fate and UMN
Fate Therapeutics (CA, USA; www.fatetherapeutics.com) has expanded its research collaboration with the Regents of the University of Minnesota (UMN; MN, USA; https://regents.umn.edu) to initiate the clinical translation of a first-of-kind product candidate, an off-the-shelf targeted natural killer (NK) cell cancer immunotherapy derived from an engineered iPSC line. The Company plans to produce the product candidate from a single iPSC that is first genetically engineered to express a high-affinity, non-cleavable CD16 (hnCD16) receptor and then is clonally-expanded to generate a master engineered pluripotent cell line. Similar to master cell lines used for the manufacture of therapeutic antibodies, a master engineered pluripotent cell line can be used to repeatedly create clonal populations of effector cells to enable off-the-shelf treatment of many thousands of patients. Preclinical production runs have shown that a single iPSC can yield a homogeneous population of over one million iPSC-derived NK (iNK) cells. NK cells have been proven to play a major role in cancer immunotherapy including antibody-dependent cellular cytotoxicity, which involves targeting of tumor cells by monoclonal antibodies for the treatment of breast, head and neck, colorectal and certain blood cancers. Activation of NK cells through CD16, a receptor that can bind to antibody-coated tumor cells, unleashes potent NK cell-mediated anti-tumor responses including direct lysis of target cells and cytokine secretion for adaptive immune cell recruitment. The Company’s hnCD16 receptor, which is licensed exclusively from UMN, incorporates two unique modifications designed to enhance the anti-tumor activity of NK cells. The receptor has been modified to augment its binding affinity to certain monoclonal antibodies, and also to prevent its shedding from the surface of NK cells upon activation which can otherwise diminish effector function.
Collaboration agreement: Orthocell and DePuy Synthes
Orthocell (Australia; www.orthocell.com.au) has announced a research collaboration agreement with DePuy Synthes (CA, USA; www.depuysynthes.com), part of the Johnson & Johnson Family of Companies (CA, USA; www.jnj.com), for its autologous tenocyte implantation, Ortho-ATI®, stem cell approach for the regeneration of degenerate tendons and ligaments. Ortho-ATI is available in Australia and New Zealand for patients who have failed conservative treatment options such as corticosteroid injections and exercise programs and have ongoing symptoms.
Collaboration and license agreement: Amgen and Immatics
Amgen (CA, USA; www.amgen.com) and Immatics Biotechnologies (Germany; http://immatics.com) have announced a research collaboration and exclusive license agreement to develop next-generation, T-cell engaging bispecific immunotherapies targeting multiple cancers. The collaboration will combine Immatics’ XPRESIDENT® target discovery and T-cell receptor (TCR) capabilities with Amgen’s validated Bispecific T-cell Engager (BiTE®) technology with the aim of creating novel oncology drugs. Amgen will be responsible for the clinical development, manufacturing and commercialization worldwide. Under the terms of the agreement, Immatics will receive an upfront fee of US$ 30 million and is eligible to receive over US$ 500 million in development, regulatory and commercial milestone payments for each program and tiered royalties up to a double-digit percentage of net sales.
Distribution agreement: HemaCare and Almog Diagnostic
HemaCare (CA, USA; www.hemacare.com) and Almog (Israel; www.almog.co.il) have established a distribution agreement. This strategic agreement ensures that the Israeli life sciences community can access HemaCare’s human healthy and disease state hematopoietic cell products for their basic scientific and cell therapy research and development needs in the right time and with local regional support.
Distribution and marketing agreement: StemBioSys and VWR
Partnership agreement: HemaCare and OneBlood
HemaCare (CA, USA; www.hemacare.com) has announced a strategic partnership with and investment by a wholly-owned subsidiary of OneBlood (FL, USA; www.oneblood.org), a not-for-profit blood center. HemaCare’s network of FDA-registered, GMP/GTP-compliant collection centers ensures donor material is available for fresh shipment to customers, as well as for internal use within HemaCare’s isolation laboratory. In this isolation laboratory, human biological material such as peripheral blood, bone marrow, and cord blood from donor and patient subjects, is isolated into various primary cell types for distribution to customers in fresh and frozen formats. OneBlood is a not-for-profit 501(c)(3) that serves more than 200 hospital partners throughout most of Florida and into parts of southern Georgia and Alabama. OneBlood distributes more than one million blood products annually, employs more than 2,000 people, operates more than 80 donor centers and deploys nearly 200 blood mobiles throughout its service area for blood drives.
Partnership agreement: Kite and Daiichi Sankyo
Kite Pharma (CA, USA; www.kitepharma.com) has entered into strategic partnership with Daiichi Sankyo (Japan; www.daiichisankyo.com) for axicabtagene ciloleucel in Japan. Axicabtagene ciloleucel, Kite’s lead product candidate, is an investigational therapy in which a patient’s T cells are engineered to express a chimeric antigen receptor (CAR) to target the antigen CD19, a protein expressed on the cell surface of B-cell lymphomas and leukemias, and redirect the T cells to kill cancer cells.
Frequency Therapeutics (CT, USA; www.frequencytx.com) has announced that a team led by Frequency’s scientific co-founders published research highlighting a breakthrough small-molecule approach to regenerate inner ear sensory hair cells . Frequency is advancing the approach to develop a potentially restorative treatment for chronic noise-induced hearing loss. The sensory hair cells in the hearing portion of the inner ear, or cochlea, detect sound and transmit their signal to neurons that ultimately communicate with the brain. These cells are susceptible to damage, and because these cells do not regenerate spontaneously, the number of hair cells in the ear only decreases with age. Per the World Health Organization (WHO), 360 million people worldwide have moderate or worse hearing loss, with an additional 1.1 billion people at risk for hearing loss from recreational noise alone. The ability to regenerate hair cells within the inner ear already exists in nature. Birds and amphibians are able to regenerate these cells throughout their lives, which provided the base to find similar pathways in mammals. The research team, which included collaborators from Harvard Medical School, the Massachusetts Eye and Ear Infirmary, Massachusetts Institute of Technology (MIT) and Brigham and Women’s Hospital, first focused on optimizing the expansion of Lgr5 expressing cochlear progenitor cells. With the combination of a GSK3 inhibitor to activate the Wnt signaling pathway and a histone deacetylase (HDAC) inhibitor to activate gene transcription, the research team achieved >2000-fold expansion of cochlear supporting cells compared to previous approaches. This protocol was used successfully and with consistency to generate colonies of neonatal and adult murine cells as well as primate and human progenitor cells. Furthermore, the team achieved 60-fold enhancement of hair cell production from the progenitor cells compared to current methods. The generation of new hair cells was achieved even in cochlear tissue that had been depleted of hair cells by exposure to an ototoxic antibiotic. Importantly, hair cells produced from the protocols exhibited the same physical features, gene expression, and functionality as typical cochlear hair cells.
Plasticell (UK; www.plasticell.co.uk) has announced that the Company’s founder, Dr. Yen Choo, has been named “Best CEO in the Stem Cell Industry” by European CEO magazine. This accolade in part recognizes Plasticell’s success in organic growth as well as its business model for the development of stem cell therapies and regenerative medicines. Plasticell, best known for its award-winning CombiCult® stem cell platform technology, has partnered this in the stem cell space with leading pharma and biotech companies, alongside in-house development of drug and cell-based therapies.
SanBio (CA, USA; www.sanbio.com) has announced that a recent publication of its stem cell treatment, SB623, for patients following a stroke , was the third prize winner of the 2016 Stroke Progress and Innovation Award. The Progress and Innovation Awards are offered by Stroke, a leading scientific journal addressing the diagnosis and treatment of cerebrovascular diseases, jointly with the American Heart Association and American Stroke Association. Results for subjects who completed the single arm Phase 1/2a study demonstrated statistically significant improvement in motor function, evaluated using the European Stroke Scale, National Institutes of Health Stroke Scale, the Fugl-Meyer total score and the Fugl-Meyer motor function total score. The data also showed that the treatment was generally safe and well-tolerated by the trial participants (www.clinicaltrials.gov ID: NCT01287936).
 McLean WJ, Yin X, Lu L et al. Clonal expansion of LGR5-positive cells from mammalian cochlea and high-purity generation of sensory hair cells. Cell Rep. 18(8), 1917-1929 (2017).
 Steinberg GK, Kondziolka D, Wechsler LR et al. Clinical outcomes of transplanted modified bone marrow-derived mesenchymal stem cells in stroke: A phase 1/2a study. Stroke. 47(7), 1817-24 (2016).