Industry updates from the field of stem cell research and regenerative medicine in May 2023

Business development

Collaboration agreement: CytoMed & MD Anderson Centar

CytoMed Therapeutics (Singapore; https://w2.cytomed.sg), a biopharmaceutical company focused on harnessing its licensed proprietary technologies to create novel allogeneic cell-based immunotherapies for the treatment of human cancers, today announced it has entered into a research collaboration agreement with The University of Texas MD Anderson Cancer Center (TX, USA; www.mdanderson.org), to use gamma-delta T cells (gdTc) for the treatment of acute myeloid leukemia and breast cancer [1]. CytoMed closed US$9.6 million Initial Public Offering in April 2023 [2].

Collaboration agreement: Life Edit & Novo Nordisk

Novo Nordisk (Denmark; www.novonordisk.com) and Life Edit Therapeutics (NC, USA; www.lifeeditinc.com), an ElevateBio company (NC, USA; https://elevate.bio), focused on next-generation gene editing technologies and therapeutics, have announced a research and development collaboration to discover and develop gene editing therapies against a select set of therapeutic targets [3]. As a part of agreement:

• Life Edit will receive an upfront cash payment and is eligible to receive milestone payments of US$250–335 million for each of seven development programmes, as well as tiered royalties on global net sales;

• Life Edit has the option to a global profit share on one programme;

• Novo Nordisk will make an equity investment in ElevateBio, Life Edit's parent company, as part of ElevateBio's Series D financing.

With a focus on advancing base editing capabilities, Novo Nordisk will leverage Life Edit's suite of gene editing technologies to precisely edit the genome with the aim of developing lifechanging therapies for rare genetic disorders as well as more prevalent cardiometabolic diseases.

Collaboration agreement: Mekonos & bit.bio

Mekonos (CA, USA; https://mekonos.com), a biotech platform company building the future of cell therapies on a chip, has announced a new research collaboration with bit.bio (UK; www.bit.bio), a synthetic biology company providing human cells for research, drug discovery and cell therapy [4]. The collaboration will test and optimize non-viral delivery of bit.bio's patented safe harbour gene-targeting approach opti-ox™, which is used to inducibly express transcription factor combinations to reprogram human induced pluripotent stem cells (iPSCs) [5]. Developing this approach as an alternative to viral vector delivery will enable bit.bio to precisely engineer stem cells into any mature, functional human cell type with higher efficiency, speed, and control. Mekonos' silicon nanoneedle-based delivery platform enables precisely controlled delivery of multiplexed cargo, including nuclear delivery.

Collaboration & License agreement: Janssen & Cellular Biomedicine

Janssen Biotech (PA, USA; www.janssen.com), one of the Janssen Pharmaceutical Companies of Johnson & Johnson (NJ, USA; www.jnj.com), has entered into a worldwide collaboration and license agreement with Cellular Biomedicine Group (China; www.cellbiomedgroup.com) to develop, manufacture and commercialize next-generation chimeric antigen receptor (CAR) T-cell therapies for the treatment of B-cell malignancies [6]. These investigational CD20-directed autologous CAR-Ts have demonstrated promising overall and complete response rates in phase 1 studies in patients with relapsed/refractory non-Hodgkin's lymphoma in China, with the majority of study participants having diffuse large B-cell lymphoma, the most common type of aggressive lymphoma accounting for approximately a third of B-cell lymphomas globally.

Licensing agreement: MaxCyte & Fish Therapeutics

MaxCyte (MD, USA; https://maxcyte.com), cell-engineering company providing has signed a strategic platform license with Walking Fish Therapeutics (CA, USA; www.walkingfishtx.com), a biotechnology company developing B cell-based therapeutics [7]. Under the terms of the agreement, Walking Fish obtains non-exclusive clinical and commercial rights to use MaxCyte's Flow Electroporation^® technology and ExPERT™ platform. In return, MaxCyte is entitled to receive platform licensing fees, clinical milestone payments and sales-based payments.

Partnership agreement: Pluristyx & Stemmasters

Pluristyx (WA, USA; www.pluristyx.com), a provider of genetically engineered iPSC-based technologies, and Stemmatters (Portugal; www.stemmatters.com), Contract Development and Manufacturing Organization (CDMO) focused on regenerative medicine solutions, including advanced therapy medicinal products (ATMPs), have announced a partnership to accelerate the development of iPSC-derived advanced therapies [8]. Built on the strengths of each company, this collaboration brings together complementary expertise to realize a shared vision on the future of regenerative medicine. In the scope of this partnership, Stemmatters and Pluristyx will collaborate in the advancement of next generation of iPSC-derived mesenchymal stem cells (iMSCs), engineered iMSCs and biological products produced from conditionally immortalized iMSC lines that include exosomes and conditioned media.

Research & License agreement: BrightPath & Artisan

BrightPath Biotherapeutics (Japan; www.brightpathbio.com/english/), a clinical stage biotechnology company focused on the development of cell therapies derived from invariant natural killer T (iNKT) cells, and Artisan Bio (CO, USA; https://artisancells.com), a precision genome engineering and drug-discovery company, have announced they have signed a research and licensing agreement to accelerate BrightPath's next-generation iNKT cell therapies to clinic [9].

• BrightPath to receive non-exclusive rights to Artisan's STAR-CRISPR editing platform to accelerate development of BrightPath's invariant natural killer T (iNKT) cells;

• Artisan to receive an upfront payment and research milestones, plus license fees, development milestones, net sales milestones, and royalty on future products.

This collaboration with Artisan provides BrightPath with the potential to create highly engineered allogeneic iNKT cellular therapy programs for a range of indications, including solid tumors. Under this agreement, BrightPath will pay Artisan an upfront payment and research milestones for the development of CRISPR guides for the editing of BrightPath's iNKT cells. BrightPath has the right to a commercial license for the STAR-CRISPR guides and nuclease for a license fee plus development milestones, sales milestones, and a royalty on future products.

Achievements, launches…

BD

BD (NJ, USA; www.bd.com), a global medical technology company, announced the worldwide commercial launch of a new-to-world cell sorting instrument featuring two breakthrough technologies that enable researchers to uncover more detailed information about cells that was previously invisible in traditional flow cytometry experiments [10]. With BD CellView™ Image Technology, researchers can see detailed microscopic images of individual cells and sort at high speeds based on visual characteristics to confirm insights in real time. With BD SpectralFX™ Technology, researchers can achieve full-spectrum cell sorting, coupled with expanded performance enabled by a new modular optical architecture and system-aware algorithms, to perform high-parameter experiments within a simplified workflow. The combination of these technologies in the BD FACSDiscover™ S8 Cell Sorter expands capabilities for researchers, introducing the potential to transform research and cell-based therapeutic development across numerous fields, including drug discovery, immuno-oncology and genomics.

bit.bio

bit.bio (UK; www.bit.bio), the cell coding company, has launched its new Custom ioDisease Model Cells™ offering [11]. This offering allows scientists to commission their disease-relevant mutation of interest in bit.bio's human iPSC-derived cells powered by opti-ox technology [5].

The disease-relevant mutation is engineered into bit.bio's human ioWild Type™ cells using CRISPR/Cas9 gene editing. As disease model cells come from an identical human genetic background to ioWild Type cells, any experimental differences observed between the wild type and the disease model can be confidently attributed to the effects caused by the disease-specific mutations.

Celularity

Celularity (NJ, USA; https://celularity.com), a biotechnology company developing placental-derived allogeneic cell therapies and biomaterial products, has received a US$45 million purchase order for Celularity private label Halal-Certified biomaterial products from Jamjoom Medical Store (Saudi Arabia; www.jamjoom.com) [12]. Celularity is developing allogeneic cryopreserved off-the-shelf placental-derived cell therapies, including therapeutic programs using mesenchymal-like adherent stromal cells, CAR T-cells, and genetically modified and unmodified natural killer cells targeting indications in autoimmune, infectious and degenerative diseases, and cancer. Celularity also develops, manufactures, and commercializes innovative biomaterial products derived from the postpartum placenta.

Celularity's suite of biomaterial products that are Halal-Certified under globally recognized Circle H International standards include:

• Biovance, a decellularized, dehydrated human amniotic membrane derived from the placenta of a healthy, full-term pregnancy. Biovance is an intact, extracellular matrix structure that is indicated for use in the USA as a natural scaffold to support the body's wound healing process;

• Biovance 3L and Biovance 3L Ocular, tri-layer human amniotic membrane products focused on the surgical and ocular markets and available in both sheet and disk form;

• Interfyl^®, a human connective tissue matrix derived from the placenta of a healthy, full-term pregnancy. It is indicated for use in the USA to replace or supplement damaged or inadequate integumental tissue resulting from wounds, trauma, or surgery;

• CentaFlex^®, a decellularized human placental matrix derived from the umbilical cord that is indicated for use in the USA as a surgical covering, wrap or barrier to protect and support the repair of damaged tissue.

CHA Medical

CHA Medical & Bio Group, stem cell research company (South Korea; http://en.chamc.co.kr), announced its plan to open later this year the CHA Power Aging Research Translational Institute (CHA PARTI) in Los Angeles, CA, USA [13]. The institute will focus on advancing comprehensive stem cell treatments through stem cell and gene therapy. The facility is GMP-equivalent, equipped with a state-of-the-art micro-manipulator for the establishment of somatic cell nuclear transfer of embryonic stem cells (NT-ESCs). It also features cell culture facilities in a sterile clean laboratory (Class 100 cleanroom, ISO5). The institute will house five resident researchers dedicated to the establishment of NT-ESCs and embryonic stem cells ESCs, and gene editing research using established stem cell. The research will be conducted in consultation with Shoukhrat Mitalipov from Oregon Health & Science University (OHSU; OR, USA; www.ohsu.edu), who also serves as an advisory professor at CHA University. Additionally, the CHA Bio Complex, Korea's largest biomedical/research organization with 1,000 researchers, will also contribute to the advancements in stem cell research done by CHA PARTI.

Creative Medical

Creative Medical Technology Holdings (AZ, USA; www.creativemedicaltechnology.com), a biotechnology company focused on a regenerative approach to immunotherapy, endocrinology, urology, gynecology and orthopedics, has received confirmation that Greenstone Biosciences (CA, USA; https://greenstonebio.com) has successfully developed a human iPSC pipeline for the Company's ImmCelz^® platform [14]. ImmCelz utilizes adult stem cells derived from qualified donors to endow specific properties to the patient's immune cells. After the patient's harvested cells are incubated with the Company's cell-free reprogramming cocktail, the cells are re-injected back into the patient. These supercharged cells subsequently educate other cells of the immune system to stop attacking the body, while preserving the ability to attack foreign pathogens.

Editas Medicine

Editas Medicine (MA, USA; www.editasmedicine.com), a clinical stage genome editing company, has published the comprehensive data from a study of the proprietary SeLection by Essential-gene Exon Knock-in (SLEEK) gene editing technology [15,16].

Despite major progress in achieving gene disruption with CRISPR-Cas gene editing technologies, efficient knock-in of transgenes continues to be a significant challenge for the gene editing field. To solve this challenge, SLEEK was developed to enable high knock-in efficiency with both viral and non-viral transgene formats while also ensuring robust simultaneous expression of up to four transgene cargos.

The study demonstrated that utilizing SLEEK results in the knock-in of multiple clinically relevant transgenes through a proprietary process that specifically selects only those cells containing the knock-in cargo. This process was developed by leveraging Editas Medicine's proprietary engineered AsCas12a nuclease, which can achieve very high editing efficiency while maintaining high specificity. More than 90 percent knock-in efficiencies were observed in various clinically relevant target cells, including T cells, B cells, iPSCs, and NK cells. Additionally, SLEEK can be used to fine-tune the expression levels of transgene cargos, an important feature of next-generation cell therapies. As a demonstration of SLEEK's potential value in clinical applications, the study authors used SLEEK to generate iPSC-derived NK cells capable of high-levels of in vivo persistence and robust tumor clearance in a solid tumor animal model.

iXCells

iXCells Biotechnologies (CA, USA; www.ixcellsbiotech.com), a provider of cell products and drug discovery services to the worldwide academic, biotech and pharmaceutical communities, today announced expansion of its CRISPR-Cas9 product and custom services offering, with special focus on iPSC-derived cell models [17].

iXCells' team of scientific experts in gene editing have already introduced several iPSC derived human motor neuron disease models that include gene mutations useful for studying neurological diseases such as familial amyotrophic lateral sclerosis. For example, some of the company's products include human iPSC motor neurons derived from a genetically modified iPSC line carrying the A4V mutation in the SOD1 gene, and Human iPSC motor neurons derived from genetically modified iPSC lines carrying the different mutations in the TDP43 gene (N352S, Q331K and M337V). The company is also developing new iPSC derived disease models, such as Alzheimer's, Parkinson and Fragile X syndrome.

SNIPR Biome

SNIPR Biome (Denmark; www.sniprbiome.com), the company pioneering CRISPR-based microbial gene therapy, has published research findings from its preclinical work on SNIPR001, the first CRISPR-armed phage therapeutic developed to specifically target and remove E. coli, including antibiotic-resistant strains, in the human gastrointestinal tract [18,19].

Synthego

Synthego (CA, USA; www.synthego.com), a provider of genome engineering solutions, has opened a state-of-the-art GMP synthesis facility featuring 24/7 operations with advanced equipment and technologies, including multiple multiplexed manufacturing lines, fully automated controls, and an integrated Manufacturing Execution System [20]. This new 18,000 square-foot facility supports the growing demand for development of high-quality, CRISPR-enabled in vivo and ex vivo therapeutics by pharma and biopharma clients.

Clinical trials

Mesenchymal stromal/stem cells (MSC)

Novadip

Novadip Biosciences (Belgium; https://novadip.com), a clinical-stage biopharmaceutical company developing a new class of regenerative tissue products to accelerate healing of large bone defects and injuries in a single treatment, has announced that the first patient has been implanted with its investigational tissue regeneration product, NVD-003, in its phase 1b/2a clinical trial treating four patients with congenital pseudarthrosis of tibia [21,22]. Novadip is developing NVD-003, an autologous therapy derived from adipose stem cells, as a potential single treatment to save limbs and restore mobility in patients with congenital pseudarthrosis of tibia, a rare pediatric bone condition.

Immune cells

Bristol Myers Squibb

Bristol Myers Squibb (NJ, USA; www.bmb.com) has announced positive topline results from two studies, TRANSCEND FL and TRANSCEND NHL 001 [23–25]. Results showed both studies met the primary end point of overall response rate, with Breyanzi demonstrating statistically significant and clinically meaningful responses in relapsed or refractory FL and MCL.

TRANSCEND FL is an open-label, global, multicenter, phase 2, single-arm study to determine the efficacy and safety of Breyanzi in patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma, including follicular lymphoma and marginal zone lymphoma. The primary outcome measure is overall response rate [24]. Secondary outcome measures include complete response rate, duration of response, and progression-free survival.

TRANSCEND NHL 001 is an open-label, multicenter, pivotal phase 1, single-arm study to determine the safety, pharmacokinetics and antitumor activity of Breyanzi in patients with relapsed or refractory B-cell non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (LBCL), high-grade B-cell lymphoma, primary mediastinal B-cell lymphoma, follicular lymphoma grade 3B and mantle cell lymphoma [25]. The primary outcome measures are treatment-related adverse events, dose-limiting toxicities and overall response rate. Secondary outcome measures include complete response rate, duration of response and progression-free survival.

Breyanzi is a CD19-directed CAR T cell therapy with a 4-1BB costimulatory domain which enhances the expansion and persistence of the CAR T cells. Breyanzi is approved by the US FDA for the treatment of adult patients with LBCL, including diffuse LBCL not otherwise specified, high-grade B-cell lymphoma, primary mediastinal LBCL, and some types of follicular lymphoma grade 3B.

Breyanzi is also approved in Japan for relapsed or refractory LBCL after first-line therapy, and in Japan, Europe, Switzerland, and Canada for relapsed and refractory LBCL after two or more lines of systemic therapy.

CARsgen

CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK), a company focused on innovative CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors, has initiated patient enrollment for phase 2 of the clinical trial for CT041 in the US, for the treatment of CLDN18.2 positive advanced gastric cancer/gastroesophageal junction cancer (GC/GEJ) in patients who have failed at least two prior lines of systemic therapies [26]. CT041 is an autologous CAR T-cell product candidate against the protein CLDN18.2. Active trials in CARsgen include investigator-initiated trials [27], a Phase Ib clinical trial for advanced GC/GEJ and pancreatic cancer and a confirmatory phase II clinical trial for advanced GC/GEJ in China [28], and a phase 1b/2 clinical trial for advanced gastric or pancreatic adenocarcinoma in North America [29].

Cellenkos

Cellenkos^® (TX, USA; https://cellenkosinc.com), a clinical stage biotechnology company focused on developing allogeneic, off-the-shelf, T regulatory cell therapies for treatment of rare inflammatory diseases and autoimmune disorders, announced that it has dosed the first patient in a phase 1/1b study evaluating CK0803 for treatment of amyotrophic lateral sclerosis (ALS). CK0803 is a neurotrophic, allogeneic, umbilical cord blood-derived T regulatory (Treg) cell therapy that preferentially homes toward central nervous system, developed by using Cellenkos' proprietary CRANE™ technology, to generate disease-specific products [30,31]. The dosing of this first patient marks the beginning of a phase 1 safety run-in study of six patients, to be followed by a phase 1b randomized, double-blind, placebo control trial of CK0803 in an additional 60 patients with ALS. The treatment will include four weekly infusions followed by five monthly infusions.

CK0803 is a novel allogenic cell therapy product consisting of T regulatory cells, with a high cell surface expression of CD11a, that leverage CXCR3/CXCL10 axis. CK0803 is derived from clinical-grade umbilical cord blood units and manufactured using Cellenkos' proprietary CRANE™ process. There is no requirement for HLA or ABO matching of CK0803 to the recipient. Multiple doses of CK0803 can be manufactured from a single umbilical cord blood unit, where the final cryopreserved product is readily available for use, at the point of care, which makes it an ideal therapy that can be infused intravenously, in the outpatient setting.

Gracell

Gracell Biotechnologies (China; www.gracellbio.com), a clinical-stage biopharmaceutical company dedicated to developing highly efficacious and affordable cell therapies for the treatment of cancer and autoimmune diseases, has announced the start of an investigator-initiated trial in China of GC012F, the Company's autologous FasTCAR therapeutic candidate dual-targeting B cell maturation antigen (BCMA) and CD19, for the treatment of refractory Systemic Lupus Erythematosus [32,33].

Verismo

Verismo Therapeutics (PA, USA; https://verismotherapeutics.com), a clinical-stage CAR-T company developing novel KIR-CAR platform technology, has activated its STAR-101 Phase 1 clinical trial [34,35].

STAR-101 will evaluate Verismo's lead candidate, SynKIR™-110, an investigational new drug for the treatment of mesothelin-overexpressing malignant pleural mesothelioma, cholangiocarcinoma and ovarian cancer. Verismo Therapeutics is conducting a Phase 1 multicenter clinical trial in these tumor types to evaluate the feasibility and safety of SynKIR-110.

Other

Creative Medical

Creative Medical Technology Holdings (AZ, USA; www.creativemedicaltechnology.com), a biotechnology company focused on a regenerative approach to immunotherapy, endocrinology, urology, gynecology, and orthopedics, has announced positive top line pilot study results for the StemSpine^® procedure using AlloStem™ to treat chronic lower back pain [36]. The data demonstrated significant efficacy and no serious adverse events using the StemSpine^® ultrasound guided non-surgical procedure for treating chronic lower back pain.

The StemSpine procedure using AlloStem resulted in a greater than 90% reduction in narcotic usage, greater than 80% reduction in pain score, and greater than 50% reduction in the Oswestry Score in the treated patients. No patients required re-dosage or surgical intervention at the primary end point of six months and there were no safety related concerns. StemSpine using AlloStem is a patented procedure that utilizes an ‘off the shelf, ready-to-use' universal and proprietary allogenic (donor) cell developed by the Company and trademarked as AlloStem. The patent issued to StemSpine includes both the use of autologous and allogenic cells.

Seres

Seres Therapeutics (MA, USA; www.serestherapeutics.com), a microbiome therapeutics company, has reported initial clinical data about SER-155 [37,38]. SER-155 is an oral, cultivated bacterial consortia investigational therapeutic designed to prevent enteric-derived infections and resulting blood stream infections, as well as induce immune tolerance responses to reduce the incidence of graft-versus-host disease (GvHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Gastrointestinal (GI) microbiome data from the first 100 days post HSCT in Cohort 1 of the SER-155 phase 1b open-label study showed the successful engraftment of SER-155 bacterial strains and a substantial reduction in the cumulative incidence of pathogen domination, a biomarker associated with the risk of serious enteric infections and bloodstream infections, as well as GvHD. The tolerability profile observed was favorable, with no serious adverse events attributed to SER-155 administration. Enrollment in the placebo-controlled Cohort 2 portion of the study is ongoing and topline results are anticipated in mid-2024.

SER-155 is an investigational, oral, 16 strain, cultivated microbiome therapeutic designed to prevent colonization and reduce the abundance of ESKAPE pathogens (e.g., from families such as Enterococcaceae, Enterobacteriaceae, Streptococcaceae, Staphylococcaceae) in the GI tract to reduce the risk of enteric driven bloodstream infections and other downstream consequences, such as GvHD, in patients receiving allo-HSCT. SER-155 has the potential to impact antimicrobial resistance (AMR), including infections caused by carbapenem-resistant Enterobacteriaceae (CRE) and vancomycin-resistant Enterococci (VRE).

SNIPR Biome

SNIPR Biome (Denmark; www.sniprbiome.com), the company pioneering CRISPR-based microbial gene therapy, had announced positive interim clinical results from its phase 1 clinical trial with SNIPR001, the first CRISPR-armed phage therapeutic developed to specifically target and remove E. coli, including antibiotic-resistant strains, from the human gastrointestinal tract [39,40].

The study, with 36 healthy individuals across three dose levels of SNIPR001, showed that oral dosing over seven days was well tolerated with only mild to moderate side effects and no withdrawals. Furthermore, SNIPR001 could be recovered in feces from treated individuals in a dose dependent manner, and treatment with SNIPR001 numerically lowered gut E. coli levels.

These findings demonstrate clinical proof of principle for this new technology, and future studies are now being planned to evaluate the impact of SNIPR001 on reducing the rate of infections in cancer patients at high risk of E. coli gut translocation into the bloodstream. In addition, the phase 1 results support development of an intravenously administered version of SNIPR001, and clinical investigations for this therapy are being planned.

Regulations, approvals, acquisitions…

Green light

Bristol Myers Squibb

Bristol Myers Squibb (NJ, USA; www.bmb.com) has announced that the European Commission (EC) has granted approval for Breyanzi (lisocabtagene maraleucel; liso-cel), a CD19-directed CAR T cell therapy, for the treatment of adult patients with diffuse LBCL, high grade B-cell lymphoma, primary mediastinal large B-cell lymphoma and follicular lymphoma grade 3B, who relapsed within 12 months from completion of, or are refractory to, first-line chemoimmunotherapy [41]. This approval covers all EU member states.

ImmPACT Bio

ImmPACT Bio (CA, USA; https://immpact-bio.com), a clinical-stage company developing transformative logic-gate-based CAR T-cell therapies for treating cancer and autoimmune diseases, has announced that the US FDA has granted Fast Track Designation for IMPT-314, a potential first-in-class CD19/CD20 CAR T therapy for the treatment of patients with B-cell mediated malignancies [42]. These include relapsed or refractory aggressive B-cell lymphoma, diffuse large B-cell lymphoma not otherwise specified or arising from follicular lymphoma after two or more lines of systemic therapy, high-grade B cell lymphoma, and primary mediastinal B-cell lymphoma.

Kimera Labs

Kimera^® Labs (FL, USA; https://kimeralabs.com), a MSC exosome research lab and producer, has announced the FDA Investigational New Drug approval of its exosomes in a phase I/IIa clinical trial [43]. The trial will assess the safety and efficacy of a single intravenous dose of an isolated, proprietary placental cell line derived, MSC extracellular vesicles for the treatment of COVID-19 symptoms in adults with mild to moderate illness.

Krystal Biotech

Krystal Biotech (PA, USA; www.krystalbio.com), a biotechnology company focused on developing and commercializing genetic medicines for patients with rare diseases, has announced the US FDA has approved VYJUVEK™ (beremagene geperpavec-svdt) for the treatment of patients 6 months of age or older with dystrophic epidermolysis bullosa (DEB) [44]. VYJUVEK is designed to address the genetic root cause of DEB by delivering functional copies of the human COL7A1 gene to provide wound healing and sustained functional COL7 protein expression with redosing. VYJUVEK is the first-ever redosable gene therapy and the first and only medicine approved by the FDA for the treatment of DEB, both recessive and dominant, that can be administered by a healthcare professional in either a healthcare professional setting or in the home.

DEB is a rare and serious disease that affects the skin and mucosal tissues caused by one or more mutations in the COL7A1 gene. The COL7A1 gene is responsible for the production of functional COL7 protein that forms anchoring fibrils necessary to bind the dermis (inner layer of the skin) to the epidermis (outer layer of the skin). The lack of functional anchoring fibrils in DEB patients leads to extremely fragile skin that blisters and tears with minor friction or trauma. DEB patients suffer from open wounds, which lead to recurrent skin infections and fibrosis that can cause fusion of fingers and toes, and ultimately increase the risk of developing an aggressive form of skin cancer.

The FDA approval of VYJUVEK is based on two clinical studies. The GEM-1/2 trial was an intra-patient, open label, single center, randomized, placebo-controlled study showing that repeat topical applications of VYJUVEK were associated with durable wound closure, full-length cutaneous COL7 expression, and anchoring fibril assembly with minimal reported adverse events [45,46]. The GEM-3 trial was an intra-patient, double-blinded, multi-center, randomized, placebo-controlled study that met both its primary end point of complete wound healing at six months and its key secondary end point of complete wound healing at 3 months [47,48]. VYJUVEK was well tolerated with no drug-related serious adverse events or discontinuations due to treatment-related events.

Neuralink

Neuralink (CA, USA; https://neuralink.com/), the brain-computer interface company, has received approval from the US FDA to conduct its first in-human clinical study [49]. The brain implant hermetically sealed in a biocompatible enclosure, contains advanced, custom-made, low-power chips and electronics that records neural activity through 1024 electrodes distributed across 64 threads. These highly-flexible, ultra-thin threads process neural signals, transmitting them wirelessly to the Neuralink App, which decodes the data stream into actions. It aims to help patients with severe paralysis regain their ability to communicate by controlling external technologies using only neural signals. Patients will be able to control external mice and keyboards through a Bluetooth connection. The extent of the approved trial is not known.

Capital market & finances

AVROBIO

AVROBIO (MA, USA; www.avrobio.com), a clinical-stage gene therapy company working to free people from a lifetime of genetic disease, has agreed to sell its investigational hematopoietic stem cell (HSC) gene therapy program for the treatment of cystinosis to Novartis [Switzerland; www.novartis.com) for US$87.5 million in cash [50]. AVROBIO retains full rights to its portfolio of first-in-class HSC gene therapies for Gaucher disease type 1 and type 3, Hunter syndrome and Pompe disease. Proceeds from this transaction are expected to extend the Company's cash runway into the fourth quarter of 2024.

Citius

Citius Pharmaceuticals (NJ, USA; https://citiuspharma.com), a late-stage biopharmaceutical company dedicated to the development and commercialization of first-in-class critical care products, has closed its previously announced registered direct offering for the purchase of an aggregate of 12,500,001 shares of its common stock at a price of US$1.20 per share and accompanying warrant [51]. The aggregate gross proceeds to the Company from the offering were approximately US$15 million, before deducting the placement agent fees and other offering expenses payable by the Company. Citius currently intends to use the net proceeds from the offering for general corporate purposes, including pre-clinical and clinical development of its product candidates and working capital and capital expenditures. Citius used a mRNA reprogramming technique to create and expanded a clonal iPSC Master Cell Bank under cGMP guidelines.

Deepcell

Deepcell (CA, USA; https://deepcell.com), a life science company pioneering AI-powered single-cell classification and isolation for basic and translational research, has closed its US$73 million Series B round of financing [52]. The new funding will allow Deepcell to continue product development and enable early commercial introduction of a new standard for obtaining biological insights from single cell analysis. Deepcell's platform combines advances in AI, proprietary microfluidics, high resolution optics, and a growing cell atlas with over 1 billion images to analyze and sort cells based on visual features. This allows researchers to characterize and gain new insights from single cells at levels of resolution previously unseen with other 'omics'-based tools.

Elevate Bio

ElevateBio (NC, USA; https://elevate.bio), a company focused on powering the creation of life-transforming cell and gene therapies, has closed its US$401 million Series D financing [53]. Proceeds from the financing will be used to further advance the company's technology platforms – Life Edit gene editing, iPSCs, and RNA, cell, protein, vector engineering – and BaseCamp^®, its end-to-end genetic medicine current Good Manufacturing Practice (cGMP) manufacturing and process development business, to accelerate the design, manufacturing, and development of cell and gene therapies. The funding will also support ElevateBio's continued efforts to expand its geographic reach and increase its cGMP manufacturing capacity to provide its academic and industry partners with turnkey and scalable access to technologies and services across the full-product lifecycle.

Ensoma

Ensoma (MA, USA; https://ensoma.com), a genomic medicines company developing one-time, in vivo treatments that precisely engineer any cell of the hematopoietic system, has closed an extension of its Series B financing by US$50 million, bringing the total size of the funding round to US$135 million [54]. The funds will be used to advance the development of Ensoma's Engenious™ in vivo engineered cell therapy platform and pipeline of genomic medicines for immuno-oncology, genetic disease and other therapeutic applications.

Krystal Biotech

Krystal Biotech (PA, USA; www.krystalbio.com), a biotechnology company focused on developing and commercializing genetic medicines for patients with rare diseases, has entered into a securities purchase agreement for the sale of 1,729,729 shares of its common stock at $92.50 per share in a private placement to certain qualified institutional buyers [55]. Expected gross proceeds were approximately US$160 million, before deducting any offering-related expenses.

Legend

Legend Biotech (NJ, USA; https://legendbiotech.com), a global biotechnology company developing, manufacturing and commercializing novel therapies to treat life-threatening diseases, has agreed to sell 5,468,750 American Depositary Shares (ADS), each representing two ordinary shares of the Company, at a price of US$64.00 per ADS, in a registered direct offering [56]. The gross proceeds of the offering are expected to be approximately US$350 million, before offering expenses, which together with the Company's existing cash and cash equivalents, will enable the Company to fund its planned operating expenses and capital expenditures through the fourth quarter of 2025.

Seres

Seres Therapeutics (MA, USA; www.serestherapeutics.com), a microbiome therapeutics company, has received a US$125 million milestone payment from Nestlé Health Science related to the US FDA approval of VOWST™ (fecal microbiota spores, live-brpk), an orally administered microbiota-based therapeutic to prevent recurrence of C. difficile Infection (CDI) in adults following antibiotic treatment for recurrent CDI [57].

The approval milestone follows the July 2021 agreement between Seres and Nestlé Health Science to jointly commercialize VOWST in the USA and Canada. Following VOWST commercialization, each company will be entitled to share equally in commercial profits and losses. In addition, Seres is eligible to receive payments of up to US$225 million for the achievement of specified net sales milestones.