Industry updates from the field of stem cell research and regenerative medicine in May 2022

Business development

Collaboration agreement: Be Bio & Resilience

Be Biopharma (MA, USA; www.be.bio) and National Resilience (CA, USA; https://resilience.com) have announced a strategic collaboration to advance initial programs in Be Bio's rare disease pipeline [1]. Be Bio's proprietary engineered B Cell Medicines (BeCM) platform is harnessing the power of the human B cell to create a new class of autologous and allogeneic cellular medicines that produce therapeutic proteins in vivo without toxic pre-conditioning.

The two companies are investing to drive innovation and reliability in cell therapy manufacturing, a critical success factor for broad and meaningful patient impact. As part of this unique partnership, Resilience will dedicate personnel solely to produce and supply Good Manufacturing Practices (GMP)-grade viral vector and cell therapy drug product for the initial programs in Be Bio's rare disease pipeline. Through a creative cost and risk-sharing model, Resilience will be responsible for manufacturing costs and receive potential future milestones and royalties. Resilience will lead clinical GMP manufacturing of both the viral vector and the cell therapy drug product for Be Bio's initial rare disease programs to support first-in-human clinical trials.

Collaboration agreement: Gilead & Dragonfly

Gilead Sciences (CA, USA; www.gilead.com) and Dragonfly Therapeutics (MA, USA; www.dragonflytx.com) have announced a collaboration designed to advance a number of Dragonfly's novel natural killer (NK) cell engager-based immunotherapies for oncology and inflammation indications [2]. NK cell engagers represent a novel mechanism with the potential to address a broad range of cancers, including potential for activity in checkpoint resistant and refractory tumors, as well as other disease areas such as inflammation. Under the agreement, Gilead will receive an exclusive, worldwide license from Dragonfly for the 5T4-targeting investigational immunotherapy program, DF7001. The agreement also grants Gilead options, after the completion of certain preclinical activities, to license exclusive, worldwide rights to develop and commercialize additional NK cell engager programs using the Dragonfly Tri-specific NK Engager (TriNKET™) platform. TriNKETs are activators of the innate and adaptive immune systems, recruiting NK and cytotoxic T cells into the tumor microenvironment.

DF7001 is a TriNKET designed to activate and direct NK and cytotoxic T cell killing against cancer cells. The target of DF7001 is 5T4, a protein expressed on cancer cells and stromal cells that support tumor growth associated with poor prognosis in several cancers, including non-small cell lung cancer, pancreatic cancer, breast cancer, and head and neck squamous cell carcinomas. DF7001 has the potential to trigger the killing of 5T4+ expressing cells, including tumor cells, cancer-associated fibroblasts and cancer stem cells. The program is on track for filing an Investigational New Drug (IND) application in the first half of 2023.

Collaboration agreement: Umoja & Lupagen

Umoja Biopharma (WA, USA; www.umoja-biopharma.com), an immuno-oncology company pioneering off-the-shelf, integrated therapeutics that reprogram immune cells in vivo for patients with solid and hematologic malignancies, and Lupagen (TX, USA; www.lupagen.com), a gene therapy company developing first-in-class gene delivery technologies for CAR-T, gene editing and immunotherapy products, have entered into a collaboration to evaluate extracorporeal in vivo delivery as a potential additional route of administration for Umoja's VivoVec particles using Lupagen's Side CAR-T™ technology [3]. Lupagen's patient connected extracorporeal Side CAR-T™ delivery system is expected to enable efficient and highly controlled viral vector targeting of T cells in a convenient bedside procedure without requirements for lymphodepleting chemotherapy. Under the terms of the agreement, both parties will collaborate to evaluate VivoVec delivery using the Side CAR-T™ system. Lupagen will not develop or commercialize the Side CAR-T™ device for the delivery of viral vectors in the field of oncology during the term of the agreement. Umoja retains the right to opt in to an exclusive, worldwide agreement to develop the Side CAR-T™ device in the field of oncology.

Partnership agreement: Evotec & Sernova

Evotec (Germany; www.evotec.com) and Sernova (ON, Canada; www.sernova.com) have announced a partnership in the field of diabetes [4]. Both Companies will leverage their respective strengths to develop an implantable induced pluripotent stem cell (iPSC)-based beta cell replacement therapy for the treatment of insulin-dependent diabetes, including type 1 and 2.

The partnership leverages iPSC-based beta cells from Evotec's QRbeta initiative. Evotec reliably produces human iPSC-based beta cells in islet-like clusters in a quality controlled (“QC”) scalable bioreactor process. Those islet-like clusters are functionally equivalent to primary human islets in their ability to normalise blood glucose levels in in vivo models over several months.

Evotec's iPSC-based beta cells will be combined with Sernova's proprietary Cell Pouch™, which is the leading implantable and scalable medical device in its class. In particular, it enables vascularisation of the cell implant and thus ensures long-term survival and optimal function in patients. The combination of primary donor islets and Cell Pouch has achieved long-lasting therapeutic results in patients enrolled in Sernova's US-based phase I/II clinical trial, including sustained insulin-independence in high-risk Type 1 diabetes (T1D) patients who previously required insulin injections for survival. Moreover, Sernova will evaluate local immune protection technology to protect non-modified beta cells and avoid the requirement for immunosuppressive treatment. The goal of the partnership is the development of an off-the-shelf iPSC-based beta cell replacement therapy device for the treatment of patients living with insulin-dependent diabetes.

Sernova has acquired an option for an exclusive global license to Evotec's Induced Pluripotent Stem Cell (iPSC)-based Beta cells for use with its Cell Pouch system to treat diabetes. From an operational perspective, the pre-clinical development programme(s) will be jointly funded until IND acceptance. Sernova has the right to exercise its option for an exclusive global license upon IND filing. Evotec will contribute cell manufacturing through commercialisation and decide in the future on joint funding of clinical development. Upon commercialisation, there will be a profit-sharing arrangement between the two companies, with the split dependent upon Evotec's participation in the clinical development programme. In conjunction with the agreement, Evotec has committed to a strategic US$ 21 (€20) million equity investment in Sernova.

Launching new products, services

Accelerated Biosciences & Pluristyx

Accelerated Biosciences (CA, USA; www.acceleratedbio.com), a regenerative medicine innovator in the use of proprietary human trophoblast stem cells (hTSCs), has announced an agreement with Pluristyx (WA, YSA; www.pluristyx.com) an advanced therapy tools and services biotechnology company, to provide iPSCs derived from hTSCs procured under Good Tissue Practices (GTP) for research evaluation [5]. As Accelerated Biosciences' contract development and manufacturing company (CDMO) partner, Pluristyx reprogrammed hTSCs to induced pluripotent stem cells (iPSCs) with a footprint-free, proprietary mRNA method. hTSC-iPSCs are available in Pluristyx's unique Ready-to-Differentiate^® format (RTD^®), allowing for rapid evaluation by eliminating the need for expansion out of thaw. Because hTSC-iPSCs are sourced under GTP, commercial partners can transition to a clinical-grade version when appropriate.

bit.bio

bit.bio (UK; www.bit.bio), a synthetic biology company working on developing and providing every human cell type at scale, with the aim of transforming the research and medicine landscape, has launched its ioGlutamatergic Neurons HTT50CAG/WT cells to advance research and accelerate drug discovery for Huntington's disease [6]. This disease model, one of the first of its kind to be commercially available, accurately reflects the genetics of the disease.

This is the pioneer product from bit.bio's new ioDisease Model portfolio, a range of cells which have specific disease-associated mutations, that can replicate human diseases in vitro and can be matched to an isogenic wild type control. The cells are iPSC-derived, generated using bit.bio's opti-oxTM1 precision cellular reprogramming technology in combination with CRISPR/Cas9-based gene editing.

EdiGene

EdiGene (China; www.edigene.com), a global, clinical-stage biotechnology company focused on translating gene-editing technologies into transformative therapies for patients with serious genetic diseases and cancer, has presented getools (gene editing data analysis toolkit) for advanced analytics of DNA and RNA editing efficiency and outcomes for therapeutic development at the American Society of Gene & Cell Therapy (ASGCT) Annual Meeting in Washington, D.C, USA [7].

Powered by internally developed algorithm framework, getools enables more efficient and accurate analytics of the mixed complex mutational spectrum in vitro and in vivo, in bulk or at the single-cell level, of DNA and RNA editing efficiency and outcomes than other existing analytic tools. It ensures data security with localized deployment and provides reports and industry-standard result files of different formats for whole-cycle data tracing and workflow integration. These features contribute to gene editing studies from lab research to therapeutic development.

SQZ Biotechnologies

SQZ Biotechnologies (MA, USA; https://sqzbiotech.com) has presented data demonstrating that the company's first generation, integrated point-of-care (POC) cell therapy manufacturing system demonstrated superior process performance and comparable or improved product specifications relative to current clean room-based processes used in clinical development [8]. The non-clinical studies showed that the SQZ^® POC system could produce the company's red blood cell derived SQZ Activating Antigen Carrier (AAC) therapeutic candidate for the treatment of HPV16 positive solid tumors in half the time (under 6 h), with 90% fewer operator hours, while producing comparable drug product. The system is also compatible with hematopoietic stem cells and peripheral immune cells, including B cells, T cells, NK cells, and monocytes.

Clinical trials

Pluripotent stem cells

Lineage cell therapeutics

Lineage Cell Therapeutics (CA, USA; https://lineagecell.com), a clinical-stage biotechnology company developing allogeneic cell therapies for unmet medical needs, has announced that results from the primary end point, safety and tolerability 1 year post-transplant, in the ongoing phase I/IIa clinical study of RG6501 (OpRegen), a retinal pigment epithelial cell therapy currently in development for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD), offer the promising demonstration that OpRegen may be able to impact GA disease progression in a clinically meaningful manner, particularly when delivered on-target and in earlier disease [9,10]. Summary of Safety Results:

• All 24 treated patients reported at least one adverse event (AE) and at least one ocular AE;

• The majority of AEs reported with OpRegen were mild (Cohort 1-3, 87%; Cohort 4, 93%), and the immunosuppressive regimen was well tolerated;

• Ocular Aes observed with OpRegen were mainly related to the surgical procedures used for subretinal delivery, with the most common being conjunctival hemorrhage/hyperemia (n = 17) and epiretinal membrane (n = 16);

• One patient discontinued the study due to an AE that was unrelated to treatment;

• No cases of rejection, acute or delayed intraocular inflammation, or sustained increases in intraocular pressure following OpRegen subretinal delivery have been reported.

Summary of Activity Results:

• Preliminary evidence of improvement in visual function was observed in patients with GA and impaired vision at baseline (Cohort 4 [n = 12]);

• Patients in Cohort 4 had an average 7.6 letter gain in visual acuity at 12 months in the study eye;

• Three patients in Cohort 4 (25%) had a 15 letter or greater gain in visual acuity at 12 months in the study eye;

• Five patients in Cohort 4 with OpRegen delivered to most or all of the GA area, including the fovea, had greater gains in visual function (average 12.8 letter gain), with evidence for regions of apparent improvement of outer retinal structure as assessed by Spectral Domain Optical Coherence Tomography (SD-OCT).

The SD-OCT imaging analysis is ongoing.

RG6501 (OpRegen) is currently being developed under an exclusive worldwide collaboration between Lineage, Roche (Switzerland; www.roche.com), and Genentech (CA, USA; www.gene.com), a member of the Roche Group.

Vertex

Vertex Pharmaceuticals (MA, USA; www.vrtx.com) provided updates on its phase I/II clinical trial of VX-880, an investigational stem cell-derived, fully differentiated pancreatic islet cell replacement therapy for people with T1D with impaired hypoglycemic awareness and severe hypoglycemia [11,12]. Two patients in Part A received VX-880 at half the target dose. The first patient dosed in Part A of the study achieved insulin independence at Day 270, with a HbA1c of 5.2%. The second patient dosed in Part A has shown robust increases in fasting and stimulated C-peptide, and reductions in exogenous insulin requirements through Day 150. Taken together, the data from the first two patients in Part A established proof-of-concept for VX-880. Per the study protocol, the Independent Data Monitoring Committee reviewed the totality of the safety and efficacy data from the first two patients dosed in Part A of the study and recommended advancement to Part B, where patients receive the full target dose of VX-880. The first patient to receive the full target dose has achieved the Day 29 follow-up milestone. VX-880 is delivered by an infusion into the hepatic portal vein and requires chronic immunosuppressive therapy to protect the islet cells from immune rejection.

Across the program, VX-880 has been generally well tolerated to date. There have been no serious adverse events (SAEs) considered related to VX-880. The majority of adverse events (AEs) were mild or moderate in all patients treated to date. The safety profile was generally consistent with the immunosuppressive regimen used in the study and the perioperative period.

The company also announced the VX-880 phase I/II study has been placed on clinical hold in the US by the FDA due to a determination that there is insufficient information to support dose escalation with the product.

Mesenchymal stromal/stem cells

Therapeutic solutions international

Therapeutic Solutions International (CA, https://therapeuticsolutionsint.com) has announced the launching of a double-blind, randomized, placebo controlled, multicenter, multination, clinical trial of 128 patients with COVID-19 associated lung failure [13]. The study will be comprised of two groups, JadiCell™ treatment group and control group. The primary end point of the study is comparing the proportion of patients alive and free of respiratory failure at Day 60 after treatment with JadiCells as compared with placebo. The Jadi Cell product, which belongs to the MSC family of cells, is a unique adult stem cell, which produces higher levels of therapeutic factors compared with other stem cells [14].

Hematopoietic stem cells

AVROBIO

AVROBIO (MA, USA; www.avrobio.com), a clinical-stage gene therapy company, has reported new interim data, including on new visual motor integration, motor coordination and visual perception measures, from a collaborator-sponsored, ongoing phase I/II gene therapy clinical trial of AVR-RD-04, an investigational gene therapy for cystinosis [15–17]. The collaborator-sponsored phase I/II clinical trial is evaluating the safety and efficacy of AVR-RD-04 in adult patients diagnosed with the infantile form of cystinosis who previously had been treated with the current standard of care (SOC) cysteamine. AVR-RD-04 genetically modifies patients' own hematopoietic stem cells (HSC) to express a functional version of cystinosin, the protein that is deficient in people living with cystinosis. Preliminary data suggest that post gene therapy, functional cystinosin has been produced throughout the body as evidenced by clinical measures in multiple tissues, including the eyes, skin, gastrointestinal mucosa, and neurocognitive system. No AEs related to the drug product have been reported to date. All five patients dosed to date remain off oral cysteamine.

Immune cells

BMS

Bristol Myers Squibb (NY, USA; www.bms.com) has announced results from the primary analysis of PILOT, a multicenter, phase II study evaluating Breyanzi (lisocabtagene maraleucel) in adults with refractory or relapsed large B-cell lymphoma (LBCL) after first-line therapy who were not deemed candidates for high-dose chemotherapy and hematopoietic stem cell transplant (HSCT) [18,19]. The PILOT study is the only company-sponsored trial to evaluate a CAR T cell therapy as a second-line treatment for patients with relapsed or refractory LBCL who are not considered candidates for stem cell transplant. The PILOT study enrolled a broad patient population of adults with refractory or relapsed LBCL after first-line treatment who were not considered candidates for transplant based on age, performance status and/or organ function and comorbidities, and regardless of time to relapse following first-line treatment. With a median follow-up of 12.3 months, the majority of patients treated with Breyanzi (n = 61) saw a reduction in disease, with 80% of patients responding to treatment. In the PILOT study, Breyanzi showed a manageable safety profile with no new safety signals and low rates of severe cytokine-release syndrome (CRS) or neurologic events, and no grade 4/5 CRS or neurologic events reported. Breyanzi, a differentiated CD-19 directed CAR T cell therapy, is currently approved by the FDA for the treatment of adult patients with relapsed or refractory LBCL after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B. Breyanzi is not indicated for the treatment of patients with primary central nervous system lymphoma.

Umoja

Umoja Biopharma (WA, USA; www.umoja-biopharma.com), an immuno-oncology company pioneering off-the-shelf, integrated therapeutics that reprogram immune cells in vivo for patients with solid and hematologic malignancies, announced activation of the phase I ENLIGHTen clinical trial in patients with osteosarcoma to assess the safety and tolerability of autologous ‘universal’ CAR T cells when administered with UB-TT170, the Company's proprietary small-molecule fluorescein tag [20,21]. This follows the recent clearance of its IND application by the US FDA for UB-TT170. The trial is being conducted in partnership with Seattle Children's Therapeutics, a venture at Seattle Children's, bringing cutting edge, curative technologies and therapies to defeat pediatric cancer and other diseases that impact children.

Other

Luxa Bio

Luxa Biotechnology (South Korea), a joint venture between Y2 Solution (South Korea; http://www.y2solution.com/en/m/index.asp) and the Neural Stem Cell Institute (NSCI), Rensselaer (NY, USA; www.neuralsci.org), have announced transplantation of the cell product RPESC-RPE-4W into the first participant with dry age-related macular degeneration (dry AMD) in its phase I/IIa clinical trial being conducted at the University of Michigan Kellogg Eye Center (MI, USA; www.umkelloggeye.org) [22,23]. RPESC-RPE-4W is a cell product derived from the retinal pigment epithelium stem cell (RPESC) that is present in the adult human retina. This adult stem cell produces retinal pigmented epithelium (RPE) cell progeny (RPESC-RPE). The cell product being used in the clinical trial is a progenitor stage RPESC-RPE cell obtained after 4 weeks of differentiation (RPESC-RPE-4W). The RPESC-RPE-4W progenitor stage cell has shown increased engraftment and vision rescue compared with more mature RPE cell products.

MediWound

MediWound (Israel; www.mediwound.com), a biopharmaceutical company focused on next-generation biotherapeutic solutions for tissue repair and regeneration, has announced positive results from its US phase II clinical study of EscharEx^® for the debridement of venous leg ulcers (VLUs) [24,25]. The study met its primary end point, its key secondary end points with high degree of statistical significance, as well as its wound closure safety measurements. MediWound anticipates meeting with the US FDA in the second half of 2022, for an end-of-phase II meeting to discuss study results and a potential phase III pivotal plan for EscharEx. The study met its primary end point with a high degree of statistical significance, demonstrating that patients treated with EscharEx had a statistically significant higher incidence of complete debridement during the 14-day measurement period within up to eight applications compared with gel vehicle (EscharEx: 63% (29/46) versus gel vehicle: 30% (13/43), p-value = 0.004). EscharEx efficacy superiority remained statistically significant compared with gel vehicle after adjusting for pre-specified covariates ascribed to patient baseline characteristics, wound size, wound age and regions.

EscharEx is a bioactive therapy for debridement of chronic and other hard-to-heal wounds in advanced stages of clinical development. Designed for the outpatient setting, EscharEx is an easy-to-use concentrate of proteolytic enzymes enriched in bromelain for topical daily applications.

Regulations, approvals, acquisitions

Regulations

US FDA

US FDA's (MD, USA; www.fda.gov) Center for Drug Evaluation and Research (CDER) has launched Accelerating Rare disease Cures (ARC) Program that harnesses CDER's collective expertise and activities to provide strategic overview and coordination of CDER's rare disease activities [26]. CDER's ARC Program is governed by leadership from across CDER's Office of the Center Director, Office of New Drugs, and the Office of Translational Sciences. The program is managed by CDER's Rare Diseases Team. The ARC's mission is to speed and to increase the development of effective and safe treatment options addressing the unmet needs of patients with rare diseases. The ARC's vision is to drive scientific and regulatory innovation and engagement to accelerate the availability of treatments for patients with rare diseases.

Acquisitions & mergers

Evotec & Rigenerand

Evotec (Germany; www.evotec.com) has signed a definitive agreement under which will acquire 100% of the capital of Rigenerand (Italy; https://rigenerand-biotech.com), for a purchase price of US$24.3 (€23) million [27]. With their highly specialized team, Rigenerand operates a first-class certified facility that integrates state-of-the-art cGMP production with R&D and QC labs and development labs. The acquisition expands Evotec's cell therapy platform EVOcells by adding a dedicated, high-quality cGMP manufacturing site.

Building on its many years of experience with iPSCs, Evotec has developed EVOcells as an integrated, versatile platform for the discovery, development, and manufacturing of cell therapies. The Company's aim is to develop innovative but cost-effective therapies for large patient numbers based on human cells to cure life-threatening diseases. Evotec's current EVOcells project portfolio covers immuno-oncology, metabolic diseases, heart repair as well as exosome-based therapies. Evotec leverages the EVOcells platform for both proprietary and partnered projects and is aiming to accelerate these projects toward transformative therapies, both within existing and new disease areas.

Green light

Achilles

Achilles Therapeutics (UK; https://achillestx.com/), a clinical-stage biopharmaceutical company developing precision T cell therapies to treat solid tumors, has announced that the first patient has been dosed with personalized clonal neoantigen-reactive T cells, or cNeT, manufactured with the Company's higher-dose VELOS™ Process 2 in the ongoing phase I/IIa CHIRON clinical trial for the treatment of advanced non-small-ell lung cancer [28,29]. Additionally, following a positive review by an Independent Data Safety Monitoring Committee, the Company has initiated enrollment in Cohort B of the THETIS clinical trial to evaluate cNeT in combination with a PD-1 checkpoint inhibitor for the treatment of metastatic malignant melanoma [30].

Google

Google (CA, USA; www.google.com) announced that in July 2022, the Google Ads “Speculative and experimental medical treatment, cell therapies, and gene therapies” policy in the Healthcare and medicines policy will be updated [31].

This update will permit the promotion of FDA-licensed or approved cell or gene therapies in the United States by entities that hold the relevant FDA-issued license or approval to market that product. Entities that do not have an FDA-issued license or approval will still be unable to promote cell therapies and gene therapies on Google Ads.

Additionally, Google is clarifying their policy language to allow ads for cell or gene therapies, globally, that are exclusively educational or informational in nature, regardless of regulatory approval status.

Google will begin rolling out the policy update on July 11, 2022, with full enforcement ramping up over approximately 4 weeks.

Novartis

Novartis (Switzerland; www.novartis.com) has announced that the European Commission (EC) has approved Kymriah^® (tisagenlecleucel), a CAR-T cell therapy, for the treatment of adult patients with relapsed or refractory (r/r) follicular lymphoma after two or more lines of systemic therapy [32]. The approval follows a positive opinion in March by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) and is applicable to all 27 European Union member states plus Iceland, Norway and Liechtenstein. This approval marks the third indication for Kymriah and makes it the first CAR-T cell therapy approved in the EU for these patients, which include those with r/r FL grade 1, 2 and 3A.

3 weeks later, US FDA has also granted accelerated approval for Kymriah for the treatment of adult patients with relapsed or refractory (r/r) follicular lymphoma (FL) after two or more lines of systemic therapy [33].

Novartis was the first pharmaceutical company to significantly invest in pioneering CAR-T research and initiate global CAR-T trials. Kymriah, the first approved CAR-T cell therapy, developed in collaboration with the Perelman School of Medicine at the University of Pennsylvania (PA, USA; www.med.upenn.edu), is the foundation of the Novartis commitment to CAR-T cell therapy.

SCG Cell Therapy

SCG Cell Therapy (Singapore; www.scgcell.com) has announced that the clinical trial application for SCG101 – an autologous T-cell receptor (TCR) T cell therapy has been approved in Singapore [34]. SCG101 is being developed to treat hepatitis B virus (HBV)-related hepatocellular carcinoma – the most common form of liver cancer. The treatment recently secured IND approval from China's National Medical Products Administration (NMPA; China; http://english.nmpa.gov.cn), making it the first TCR-T cell therapy product approved by the NMPA for the treatment of HCC and the first multi-country clinical trial approval in the field of cell therapy.

With SCG101, the function of T-cells is activated by recognizing peptide fragments – short chains of amino acids - of pathogen-derived proteins in the form of complexes of peptides and major histocompatibility complex (MHC) on the cell surface via the TCR. SCG101 specifically recognizes the epitope of the HBV surface antigen (HBsAg), which redirects T-cells specificity against the HBV antigens. With the specific HLA typing, SCG101 can recognize both HBsAg membrane antigen and HBsAg intracellular antigen. Therefore, SCG101 eliminates targets HBsAg-positive HCC cells and also eradicates HBV covalently closed circular DNA (cccDNA).

Capital market & finances

Aspen Neuroscience

Aspen Neuroscience (CA, USA; https://aspenneuroscience.com), a private biotechnology company developing autologous cell therapies, including the first iPSC-derived autologous neuron replacement treatment for Parkinson's disease, has closed its Series B funding round of US$147.5 million [35]. The Series B funding will support the planned studies of the company's lead product candidate for Parkinson's disease, ANPD001, including its patient Screening Cohort study and the upcoming phase I/IIa clinical trial, post-IND submission to FDA.

Castle Creek Biosciences

Castle Creek Biosciences (PA, USA; https://castlecreekbio.com), a late-stage cell and gene therapy company using two lentiviral platforms to develop and commercialize therapies gene therapies that initially target skin, connective tissue and metabolic diseases, has announced an oversubscribed and upsized preferred stock financing of US$112.8 million [36]. The financing is expected to provide sufficient capital for the company's completion of a phase III study and issuance of topline results of its lead ex vivo product candidate for recessive dystrophic epidermolysis bullosa (RDEB), a progressive, painful and debilitating rare genetic skin disorder, and positions Castle Creek to advance it's in vivo work to submit an IND application to the US FDA for hereditary tyrosinemia type 1, its first indication using the in vivo gene therapy technology.

Japan

A group of Japanese ethics and public health academics has published article presenting financial risks posed by unproven cell intervention industry including estimation of refunds from medical expense deductions in Japan [37]. The estimated annual treatment costs for cell therapies offered as treatment under private practice in 2017 was US$63.5 million from which the patients were refunded 12.2% (US$7.8) from medical expense deductions. In 2018, the amount nearly doubled (US$114 million in costs and US$14.5 in refund).

Neurona

Neurona Therapeutics (CA, USA; www.neuronatherapeutics.com), a clinical-stage biotherapeutics company advancing regenerative cell therapies for the treatment of neurological disorders, has been awarded a US$7,999,999 grant by the California Institute for Regenerative Medicine (CIRM; CA, USA: www.cirm.ca.gov) to support a dose-escalation Phase I/II clinical trial of NRTX-1001, an inhibitory cell therapy that is being evaluated for safety and efficacy in people with drug-resistant mesial temporal lobe epilepsy (MTLE) [38,39]. MTLE primarily affects the internal structures of the temporal lobe, where seizures often begin in a structure called the hippocampus. MTLE is the most common type of focal epilepsy in adults. For people resistant to anti-seizure drugs, epilepsy surgery, where the damaged temporal lobe is surgically removed or ablated by laser, can be an option. However, the current surgical options are not available or effective for all, are tissue-destructive, and can have significant adverse effects. NRTX-1001 is a regenerative neural cell therapy derived from human embryonic stem cells. The fully-differentiated neural cells, called interneurons, secrete the inhibitory neurotransmitter GABA. Delivered as a one-time dose, the human interneurons are intended to integrate and innervate on-target, providing long-term GABAergic inhibition to repair hyperexcitable neural networks.