Industry updates from the field of stem cell research and regenerative medicine in October 2019

Business development

Collaborations, partnerships & alliances

Co-development agreement: CRISPR Therapeutics & Bayer

CRISPR Therapeutics (Switzerland; www.crisprtx.com) and Bayer (Germany; www.bayer.com) have announced proposed plans whereby Casebia Therapeutics (MA, USA; https://casebia.com), a joint venture between CRISPR Therapeutics and Bayer, would operate under the direct management of CRISPR Therapeutics [1]. Upon closing of the transaction, Casebia Therapeutics would focus on the development of its lead programs in hemophilia, ophthalmology and autoimmune diseases, with Bayer having opt-in rights for two products at Investigational New Drug (IND) submission.

Co-development agreement: Ziopharm & MD Anderson

Ziopharm Oncology (MA, USA; https://ziopharm.com/) and The University of Texas MD Anderson Cancer Center (TX, USA; www.mdanderson.org) have announced a new research and development agreement relating to Ziopharm's Sleeping Beauty immunotherapy program to use nonviral gene transfer to stably express and clinically evaluate neoantigen-specific T-cell receptors (TCRs) in T cells (referred to as TCR-T) [2]

Collaboration agreement: GSK & Lyell

GlaxoSmithKline (UK; www.gsk.com) has announced a 5-year collaboration with Lyell Immunopharma (CA, USA; https://lyell.com) to develop new technologies to improve cell therapies for cancer patients [3]. The collaboration will apply Lyell's technologies to further strengthen GSK's cell therapy pipeline, including GSK3377794, which targets the NY-ESO-1 antigen that is expressed across multiple cancer types.

To date, two cell therapies have been approved for blood-borne cancers, but engineered T cells have not yet delivered strong clinical activity in common solid tumors. Improving the ‘fitness’ of T cells and delaying the onset of T-cell exhaustion could help engineered T-cell therapies become more effective. Combining GSK's strong cell and gene therapy programs with Lyell's technologies may allow the joint research team to maximize the activity and specificity of cell therapies in solid tumor cancers, where there is a high unmet medical need.

Licensing agreement: CRISPR Therapeutics & KSQ

CRISPR Therapeutics (Switzerland; www.crisprtx.com), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, and KSQ Therapeutics (MA, USA; www.ksqtx.com), a biotechnology company using CRISPR technology to enable the company's powerful drug discovery engine to achieve higher probabilities of success in drug development, have announced a license agreement whereby CRISPR Therapeutics will gain access to KSQ intellectual property for editing certain novel gene targets in its allogeneic oncology cell therapy programs, and KSQ will gain access to CRISPR Therapeutics’ intellectual property for editing novel gene targets identified by KSQ as part of its current and future engineered tumor infiltrating lymphocyte (eTIL™) cell programs [4]. The financial terms of the agreement are not being disclosed.

Licensing agreement: Tmunity & CHOP

Tmunity Therapeutics (PA, USA; www.tmunity.com), a private clinical-stage biotherapeutics company focused on T-cell immunotherapy, has entered into an exclusive license and research collaboration agreement with Children's Hospital of Philadelphia (CHOP; PA, USA; www.chop.edu) to advance a glypican 2 (GPC2) chimeric antigen receptor T-cell (CAR-T) therapy for the treatment of neuroblastoma, a rare cancer that affects the developing nervous system [5]. The therapy also has expansion potential in medulloblastoma and small cell lung cancer, among several other pediatric and adult cancers that express an abundance of the GPC2 protein on their cell surface.

Manufacturing agreement: Mesoblast & Lonza

Mesoblast (Australia; www.mesoblast.com) and Lonza (Switzerland; www.lonza.com) have entered into an agreement for commercial manufacture of Mesoblast's lead allogeneic cell therapy product candidate, remestemcel-L for pediatric steroid-refractory acute graft versus host disease [6]. This agreement will facilitate inventory build ahead of the planned US market launch of remestemcel-L and commercial supply to meet Mesoblast's long-term market projections. Mesoblast expects to complete filing of the rolling Biologics License Application submission to the US FDA by the end of 2019. On acceptance of the filing, the product candidate is eligible for FDA priority review under its existing Fast Track designation, providing for an expedited review period. If approved, the US launch of remestemcel-L is expected to occur 2020. The agreement provides for Lonza to expand its Singapore cGMP facilities if required to meet long-term growth and capacity needs for the product. Additionally, it anticipates introduction of new technologies and process improvements which are expected to result in significant increases in yields and efficiencies.

Launching new products, services

Adaptate

GammaDelta Therapeutics (UK; https://gammadeltatx.com), a company focused on harnessing the unique properties of γδ T-cells to develop transformational immunotherapies, has announced formation of a spin-out company Adaptate Biotherapeutics (UK; www.adaptatebiotx.com) [7]. While GammaDelta Therapeutics’ primary goal is to develop γδ T-cell-based cell therapy products, the new spin-out will build on GammaDelta's knowledge to modulate γδ T-cell activity using therapeutic antibodies, with the potential to trigger an immune response against cancer. The two companies will continue sharing their insights into γδ T-cell biology as they work toward developing different therapeutic modalities.

ArsenalBio

ArsenalBio (CA, USA; https://www.arsenalbio.com) has made its debut backed by US$85 million Series A financing to build a programmable cell therapy company to create highly effective and accessible immune cell therapies [8]. The company will integrate technologies such as CRISPR-based genome engineering, scaled and high throughput target identification, synthetic biology and machine learning to advance a new paradigm to discover and develop immune cell therapies, initially for cancer. ArsenalBio's foundation stems from the contributions of scientific leaders from a consortium of academic medical and research institutions. Today's commercialized, first-generation T-cell therapies are designed and manufactured with the goal of inserting into T cells a single cell-targeting transgene, a CAR or a new TCR through viral delivery. ArsenalBio seeks to exponentially advance this process by precisely inserting, without viral vectors, significantly larger DNA payloads, designed with proprietary tools and encoding a broader set of biological ‘software’ instructions to enable immune cells to effectively target and destroy solid organ and hematologic cancers.

Gallant

Gallant (CA, USA; www.gallant.com), an animal biotech company on a mission to help pets live healthier and happier lives, has launched the first and only nationwide stem cell banking solution for dogs [9]. The company is also announcing its acquisition of the veterinary division of Cook-Regentec (IN, USA; www.cookregentec.com), including their intellectual property, existing stem cell banking operations and their pipeline of cell therapy products derived from reproductive tissue. With its patent-pending process, Gallant obtains a dog's stem cells from tissues collected during a routine spay or neuter procedure. The procedure fee costs US$395, and storage plan options include a lifetime fee of US$595 or annual fee of US$95.

HighPassBio

ElevateBio (MA, USA; www.elevate.bio) has established and launched HighPassBio, a company dedicated to advancing novel targeted T-cell immunotherapies. The company's lead product is an engineered TCR-based T-cell therapy for HA-1 expressing tumors, which is designed to treat and potentially prevent relapse of leukemia following hematopoietic stem cell transplant (HSCT) [10]. HA-1 is also known as ρ-GTPase activating protein 45 (ARHGAP45). A Phase I clinical trial has treated initial patients and is recruiting adult and pediatric patients who have relapsed with leukemia or related conditions following HSCT (www.clinicaltrials.gov; ID: NCT03326921).

Synthego

Synthego (CA, USA; www.synthego.com), the genome engineering company, has announced the launch service of genome engineering for induced pluripotent stem cells (iPSCs) [11]. Synthego's proprietary cell editing platform removes the difficulty of editing, cloning and maintaining high pluripotency in clinically relevant iPSCs, with editing rates as high as 90% prior to cloning and 100% in clones. The new offering of iPSCs includes modification by removal of gene function (knockout), single nucleotide variation, protein tagging and other knock-ins, enabling scientists to generate edits at a massive scale to accelerate research and disease modeling. The company simultaneously announced the National Institute on Aging at the NIH has awarded Synthego a contract to create panels of mutations in a variety of genetic backgrounds to study Alzheimer's disease and related dementias.

Clinical trials

Hematopoietic stem cells

AVROBIO

AVROBIO (MA, USA; www.avrobio.com) has announced that the first patient has been dosed in the Company's AVR-RD-04 investigational gene therapy program for cystinosis, a devastating lysosomal storage disease, in an ongoing Phase I/II clinical trial sponsored by academic collaborators at the University of California San Diego [12]. The gene therapy is derived from the patient's own hematopoietic stem cells, which are genetically modified to produce functional cystinosin (CTNS), a crucial protein that patients with cystinosis lack. The trial will enroll up to six patients with cystinosis, a rare inherited disease caused by a defect in the CTNS gene. The CTNS protein enables transport of the amino acid cystine out of lysosomes. When it is absent, cystine accumulates and crystalizes, causing progressive damage to the kidneys, liver, muscles, eyes and other organs and tissues. Cystinosis affects both children and adults; they face shortened life spans and often painful symptoms, including muscle wasting, difficulty breathing, blindness and kidney failure.

Jazz Pharmaceuticals

Jazz Pharmaceuticals (Dublin, Ireland; www.jazzpharma.com) has announced that the first patient has been enrolled in an exploratory Phase II clinical trial evaluating the ability of defibrotide to prevent neurotoxicity in patients with relapsed or refractory diffuse large B-cell lymphoma receiving CAR-T therapy (www.clinicaltrials.gov; ID: NCT03954106) [13]. The prospective, multicenter, open-label, single-arm study will evaluate the safety and efficacy of defibrotide in the prevention of CAR T-cell associated neurotoxicity in patients with relapsed or refractory diffuse large B-cell lymphoma receiving Gilead's (CA, USA; www.gilead.com) axicabtagene ciloleucel (YESCARTA; www.yescarta.com). Patients may experience neurotoxicity after CD19 targeted CAR-T therapy, and while the exact cause is unknown, research suggests that endothelial cell damage may play a role. Some researchers hypothesize that the damage caused by cytokine release after CAR-T therapy may compromise the ability of endothelial cells to protect the central nervous system (CNS), causing neurotoxicity. This study will explore whether defibrotide could help prevent CNS endothelial cell damage, thereby protecting the CNS and minimizing neurotoxicity. This study will be conducted in two parts, with the first part evaluating the safety of a 2.5 mg/kg/dose and a 6.25 mg/kg/dose of defibrotide based on a standard 3 + 3 design. Part two will evaluate the safety and efficacy of defibrotide at the recommended dose for the prevention of CAR-T-associated neurotoxicity. The primary end point is the incidence of CAR-T-associated neurotoxicity (any grade, defined by Common Terminology Criteria for Adverse Events v5.0) by CAR-T Day +30.

Rocket

Rocket Pharmaceuticals (NY, USA; www.rocketpharma.com), a multiplatform clinical-stage gene therapy company, has presented an updated long-term follow-up from the Phase I/II clinical trial of RP-L102 at the European Society of Cell and Gene Therapy (ESGCT) 27^th Annual Congress in Barcelona, Spain (www.esgct.eu/Congress/Barcelona-2019.aspx) [14,15]. RP-L102 is the Company's lentiviral vector–based gene therapy for the treatment of Fanconi anemia. The presentation described nine pediatric patients (age 3–7 years) who received RP-L102 utilizing fresh or cryopreserved mobilized peripheral blood CD34⁺ cells that were transduced with the therapeutic vector. Four of these patients have been followed for more than 2 years (24–39 months) and they resemble somatic mosaics indicating:

• Dose-dependent engraftment of gene corrected hematopoietic cells;

• Progressive repopulation advantage of gene-corrected hematopoietic stem and progenitor cells after 2–3 years postinfusion;

• Oligoclonal reconstitution and gene correction of multipotent hematopoietic stem cells;

• Phenotypic correction of bone marrow progenitors and peripheral blood T cells.

The Phase I/II study of RP-L102 is an ongoing, open-label, single-center study designed to evaluate the safety and efficacy of ‘Process A’ RP-L102 without the use of any conditioning regimen conventionally used in allogenic transplant (www.clinicaltrials.gov; ID: NCT03814408).

Other

Abeona

Abeona Therapeutics (NY, USA; www.abeonatherapeutics.com) has announced positive long-term efficacy and safety results from its Phase I/IIa clinical trial evaluating EB-101, a gene-corrected cell therapy for recessive dystrophic epidermolysis bullosa [16,17]. Treatment with EB-101 resulted in sustained wound healing with a favorable safety profile at 3 years post-treatment. EB-101 is an investigational, autologous, gene-corrected cell therapy poised to enter late-stage development for the treatment of recessive dystrophic epidermolysis bullosa, a rare connective tissue disorder without an approved therapy. Treatment with EB-101 involves using gene transfer to deliver COL7A1 genes into a patient's own keratinocytes and transplanting them back to the patient to enable normal type VII collagen expression and facilitate wound healing. In the US, Abeona holds regenerative medicine advanced therapy, breakthrough therapy and rare pediatric designations for EB-101 and Orphan Drug designation in both the US and EU.

Nadiya

At the American Society for Reproductive Medicine 2019 Scientific Congress and Expo in Philadelphia (PA, USA; https://asrmcongress.org), doctors from the Nadiya Clinic of Reproductive Medicine (Ukraine; https://nadiya.clinic) and their subsidiary Darwin Life Nadiya (Kiev, Ukraine; http://dl-nadiya.com/) have presented data showing that experimental and much-hyped reproductive procedure that mixes DNA from three people is not effective at boosting the chances of having a baby for women ages 37 and older [18]. Fertility experts hoped that the younger mitochondria from the hollowed-out donor egg might rejuvenate the eggs of an infertile woman, thus increasing the chances of a successful pregnancy. The procedure is banned in the US and is highly restricted in most other countries. The doctors at the Nadiya Clinic performed mitochondrial replacement therapy on 30 women aged 37–47 who were seeking treatment for infertility due to advanced age. Out of 109 lab-fertilized eggs, only 33 became embryos, and just three of those embryos were healthy enough to be implanted into patients. A fetal heartbeat was confirmed in only one patient, a 42-year-old woman who gave birth to a healthy boy in March 2018. The authors report that the child is healthy.

ReNeuron

ReNeuron Group plc (UK; www.reneuron.com) has announced new positive data in the Company's ongoing Phase I/IIa clinical trial of its human retinal progenitor cell (hRPC) therapy candidate in the blindness-causing disease, retinitis pigmentosa (www.clinicaltrials.gov; ID: NCT02464436) [19]. A total of 22 patients have now been treated in the Phase I/IIa study and a good safety profile has been established, with no patients experiencing product-related serious adverse events and two patients experiencing surgical procedure-related loss of vision. The observed efficacy was rapid and profound in the first three patients in the Phase IIa segment of the study. Efficacy in subsequent patients has also been seen but at a lower rate and magnitude (improvement in visual acuity ranging from +5 to +11 letters in the treated eye 3 months post-treatment), with the ultimate extent of improvement not yet known as the study is ongoing. Overall, the improvements to date represent a clear signal of efficacy in a patient population where inexorable disease progression is the norm.

Regulations, approvals, acquisitions

Green light

AVROBIO

AVROBIO (MA, USA; www.avrobio.com) has announced that the FDA has granted orphan-drug designation for the Company's investigational gene therapy, AVR-RD-02, for the treatment of Gaucher disease [20]. AVR-RD-02 consists of the patient's own hematopoietic stem cells, genetically modified to express glucocerebrosidase, the enzyme that is deficient in Gaucher disease. The Company is actively recruiting in Canada for its Phase I/II clinical trial of AVR-RD-02, which seeks to evaluate the safety and efficacy of the therapy in patients with Type I Gaucher disease. AVR-RD-02 is an ex vivo lentiviral-based investigational gene therapy designed to provide durable and potentially life-long therapeutic benefit for patients with Gaucher disease with a single dose of the patient's own hematopoietic stem cells. The stem cells are genetically modified to express functional glucocerebrosidase, which reduces levels of glucosylceramide and glucosylsphingosine, the accumulated substances which cause the symptoms of Gaucher disease.

bluebird

bluebird bio (MA, USA; www.bluebirdbio.com) has announced that the EMA approved the refined commercial drug product manufacturing specifications for ZYNTEGLO^™ (autologous CD34⁺ cells encoding β^A-T87Q-globin gene), a one-time gene therapy for patients 12 years and older with transfusion-dependent β-thalassemia, who do not have a β⁰/β⁰ genotype, for whom HSCT is appropriate but a HLA-matched related hematopoietic stem cell donor is not available [21]. The conditional marketing authorization is supported by efficacy, safety and durability data from the Phase I/II HGB-205 study (www.clinicaltrials.gov; ID: NCT02151526) and the completed Phase I/II Northstar (HGB-204; www.clinicaltrials.gov; ID: NCT01745120) study as well as available data from the ongoing Phase III Northstar-2 (HGB-207; www.clinicaltrials.gov; ID: NCT02906202) and Northstar-3 (HGB-212; www.clinicaltrials.gov; ID: NCT03207009) studies, and the long-term follow-up study LTF-303 (www.clinicaltrials.gov; ID: NCT02633943), as of the data cut off of 13 December 2018.

Cabaletta

Cabaletta Bio (PA, USA; https://cabalettabio.com/), a clinical-stage biotechnology company focused on the discovery and development of engineered T-cell therapies for the treatment of patients with B-cell-mediated autoimmune diseases, has received clearance of its IND application from the FDA to initiate a first-in-human clinical trial of desmoglein three chimeric autoantibody receptor T cells (DSG3-CAART) in patients with mucosal pemphigus vulgaris (mPV) to assess the safety and tolerability of DSG3-CAART in these patients [22]. The Company anticipates enrolling the first patient in 2020. While CAR T cells typically contain a CD19-targeting molecule, CAAR T cells express an autoantibody-targeted antigen on their surface. The co-stimulatory domain and the signaling domain of both a CAR T cell and a CAAR T cell carry out the same activation and cytotoxic functions. Thus, Cabaletta's CAARs are designed to direct the patient's T cells to kill only the pathogenic cells that express disease-causing autoantibodies on their surface.

mPV is a potentially fatal, B-cell-mediated chronic, rare autoimmune disease that causes painful blisters and sores on mucous membranes of affected patients, leading to severe and sometimes debilitating and life-altering effects. DSG3-CAART is designed to selectively target and eliminate B cells expressing autoantibodies specific for DSG3 that are the cause of mPV while preserving healthy B cell immune function. DSG3-CAART has the potential to generate persistent complete remission off therapy while avoiding the adverse effects of chronic and generalized immunosuppression. Currently available treatment options induce broad immunosuppression, which put the patient at risk of infection and often provide only transient complete remission with subsequent relapses for patients with moderate to severe mPV. Approximately 4250 patients suffer from mPV in the US and 6250 patients in Europe, which accounts for approximately 25% of all pemphigus vulgaris cases.

CARsgen

CARsgen Therapeutics (China; www.carsgen.com), a clinical-stage biopharmaceutical company, has announced that the FDA has granted regenerative medicine advanced therapy designation to its investigational CT053 CAR-T therapy [23]. CT053 is a fully human anti-B cell maturation antigen (BCMA) autologous CAR-T therapy for the treatment of relapsed and/or refractory multiple myeloma. The CT053 anti-BCMA CAR-T program has also received IND clearance and Orphan Drug designation from the FDA and authorization of its clinical trial application from Health Canada.

Gilead

The Scottish Medicines Consortium (SMC; UK, www.scottishmedicines.org.uk) has recommended Gilead Sciences’ (CA, USA; www.gilead.com) CAR-T therapy Yescarta^® (axicabtagene ciloleucel) for use in the National Health Service to treat relapsed/refractory diffuse large B-cell primary mediastinal large B-cell lymphoma after at least two prior lines of therapy [24]. The SMC's role is similar to The National Institute for Health and Care Excellence (NICE; UK; www.nice.org.uk), which is advising the National Health Service in England on clinical utility and cost–effectiveness of new drugs.

Ziopharm

Ziopharm Oncology (MA, USA; https://ziopharm.com/) has announced that the FDA has cleared an IND application for a Phase I clinical trial to evaluate CD19-specific CAR-T, produced using a process termed rapid personalized manufacture, as an investigational treatment for patients with relapsed CD19+ leukemias and lymphomas [25].

Capital market & finances

Arcellx

Arcellx (MD, USA; www.arcellx.com) has raised US$85 million in a Series B financing Proceeds will be used to advance the Company's ARC T sparX programs including clinical development of a bivalent BCMA targeted cell therapy in multiple myeloma and a CD123 targeted therapy in acute myeloid leukemia [26]. The Series B will also fund earlier stage ARC T sparX programs for patients with solid tumors and diseases outside oncology. Arcellx has pioneered a proprietary Soluble Protein Antigen Receptor X linker (sparX) + antigen receptor complex (ARC) T platform in which the sparX simultaneously binds one or more tumor antigens and engages a universal receptor expressed on the T cells (ARC T). The formation of a sparX + ARC T + tumor cell complex results in tumor killing. This therapeutic platform is designed to enhance safety and efficacy while accelerating development by broadening patient accessibility and increasing efficiency of manufacturing relative to existing cell therapies.

Astellas

Astellas Pharma (Japan; www.astellas.com) will invest nearly US$13 million into two innovation incubators operated by LabCentral (MA, USA; https://labcentral.org), a laboratory facility for next-generation biotech startups [27]. This initiative, combined with the more than US$1 billion Astellas has previously committed to driving innovation in Massachusetts, contributes to the Boston-area life science community's ongoing efforts to accelerate the discovery and development of potential breakthrough therapies in areas of significant unmet need. Since 2010, Astellas has invested more than US$800 million in, and committed nearly US$500 million more to, Massachusetts-based innovation through the acquisitions of Ocata Therapeutics, Mitobridge and Potenza Therapeutics, as well as the construction of a state-of-the-art headquarters for the Astellas Institute for Regenerative Medicine in Westborough, MA. The new facility, expected to open in 2020, will enable Astellas Institute for Regenerative Medicine to accelerate research and development in the field of regenerative medicine and cell therapy. The impact of this agreement on Astellas’ financial results in the fiscal year ending 31 March 2020 will be limited.

California Institute for Regenerative Medicine

The governing Board of the California Institute for Regenerative Medicine (CIRM; CA, USA; www.cirm.ca.gov) has invested US$35.4 million to fund the Stem Cell Agency's first clinical trial in Parkinson's disease, and to support three clinical trials targeting different forms of vision loss [28]. This brings the total number of clinical trials funded by CIRM to 60.

Brain Neurotherapy Bio (no website available) is using a gene therapy approach to promote the production of a protein called GDNF, which is best known for its ability to protect dopaminergic neurons, the kind of cell damaged by Parkinson’s. The approach seeks to increase dopamine production in the brain, alleviating Parkinson's disease symptoms and potentially slowing down the disease progress. The company has received US$5,510,462 to complete Phase Ib clinical trial [29].

jCyte (CA, USA; http://jcyte.com) are injecting hRPCs, into the vitreous cavity, a gel-filled space located in between the front and back part of the eye. The proposed mechanism of action is that hRPCs secrete neurotrophic factors that preserve, protect and even reactivate the photoreceptors, reversing the course of the disease. The Company has received US$8,295,750 to complete Phase II clinical trial [30].

Other awardees are academic institutions.

The CIRM Board also approved investing US$15.80 million in four awards in the Translational Research program. The goal of this program is to help promising projects complete the testing needed to begin talking to the FDA about holding a clinical trial. The only nonacademic institution, Neurona Therapeutics (CA, USA; www.neuronatherapeutics.com), has received US$4,848,750 for a development of a human stem cell-derived inhibitory neuron therapeutic for the treatment of chronic focal epilepsy.

Hrain

Hrain Biotechnology (China; www.dashengbio.com/en/), a company that specializes in the research and development of tumor immunotherapy technologies, has secured US$27.97 million (200 million yuan) in a Series B round of financing [31]. The company specializes in CAR-T technology, a type of immunotherapy that genetically engineers T cells to recognize and destroy cancers while promoting other technologies like CAR-natural killer cells, new dendritic cell vaccines and invariant natural killer T cells.

Mesoblast

Mesoblast (Australia; www.mesoblast.com) has successfully completed a US$50.8 (A$75) million capital raising via a placement to existing and new Australian and global institutional investors [32]. This placement will result in the issue of 37.5 million new fully paid ordinary shares at a price of US$1.36 (A$2.00) per share. This price represents a 3.15% discount to the 10-day volume weighted average price at the close of trading 30 September 2019. The net proceeds will principally be used to build product inventory and a targeted US sales force in preparation for the potential US commercial launch of remestemcel-L in the treatment of pediatric steroid-refractory acute graft versus host disease. Proceeds will also be used to complete Phase III trials for chronic low back pain and advanced heart failure, and for working capital and general corporate purposes.

Mogrify

Mogrify (UK; https://mogrify.co.uk) has announced the initial close of its Series A funding [33]. The Company raised US$16 million USD in this round, bringing the total investment to over US$20 million to date. The funding will support internal cell therapy programs, and the development and out-license of novel intellectual property (IP) relating to cell conversions of broad therapeutic interest. Mogrify has developed a proprietary direct cellular conversion technology, which makes it possible to transform (transmogrify) any mature human cell type into any other without going through a pluripotent stem cell- or progenitor cell-state. The Company is deploying this platform to develop novel cell therapies addressing musculoskeletal, auto-immune, cancer immunotherapy, ocular and respiratory diseases as well as generating a broad IP position relating to cell conversions that exhibit safety, efficacy and scalable manufacturing profiles suitable for development as cell therapies. Mogrify is commercializing its technology platform via a model that includes development and out-license of internally developed cell therapy assets, development and license of novel cell conversion IP and the formation of joint-ventures to exploit the platform and/or novel cell conversion IP in noncore areas.

Platelet BioGenesis

Platelet BioGenesis (MA, USA; www.plateletbiogenesis.com), the company working on stem cell-derived, on-demand human platelets (PLTs+™) and genetically engineered platelet-based therapeutics, was awarded a contract worth US$5 million, with the potential to reach US$56 million total with options, by the Biomedical Advanced Research and Development Authority (BARDA; DC, USA; www.phe.gov/about/barda/Pages/default.aspx), an agency of the US government's Department of Health and Human Services’ Office of the Assistant Secretary for Preparedness and Response [34]. Platelet BioGenesis will use the funding to develop and establish donor-independent platelets as a medical countermeasure for treating victims of a nuclear or radiological event.

Tmunity

Tmunity Therapeutics (PA, USA; www.tmunity.com), a private clinical-stage biotherapeutics company focused on T-cell immunotherapy, has closed a US$75 million Series B financing [35]. The proceeds from the Series B will continue to fund ongoing and planned research, clinical development of product candidates, the continued build-out of the Company's proprietary, vertically integrated viral vector and cell therapy product manufacturing, working capital and other general purposes. Since inception, Tmunity has raised U$231 million.