Industry updates from the field of stem cell research and regenerative medicine in July 2024

ABSTRACT

Latest developments in the field of stem cell research and regenerative medicine compiled from publicly available information and press releases from non-academic institutions in July 2024.

1. Business development

1.1. Co-development agreement: Boston Oncology & KFMC

In a landmark initiative poised to transform healthcare in the Kingdom of Saudi Arabia, Boston Oncology (MA, USA; https://bostononcology.com) and King Fahd Medical City (KFMC; Saudi Arabia; https://www.kfmc.med.sa) have signed a Letter of Intent to collaborate on the localization of Cell & Gene Therapy [1].

KFMC stands as one of the largest and most rapidly expanding medical complexes in the Middle East, with a capacity of 1200 beds. Operating within the second health cluster, KFMC consists of four hospitals and four specialized medical centers, offering comprehensive healthcare services. Known for its advanced medical technologies and high standard of care, KFMC serves over 30,000 inpatients and 500,000 outpatients annually.

1.2. Licensing agreement: Arc therapies, NCC & UPenn

The National Cancer Center (Japan; https://www.ncc.go.jp/en/index.html) and The University of Pennsylvania (PA, USA; www.upenn.edu) have licensed patent rights directed to a chimeric antigen receptor (CAR) T cell therapy that targets the chemokine receptor CCR4 (CCR4 CAR-T cell therapy) to ARC Therapies (Japan; https://arctherapies.inc/), a startup originating from the National Cancer Center [2]. This agreement marks the commencement of ARC Therapies' research and development of a cell therapy targeting T-cell cancers, including adult T-cell leukemia/lymphoma, which is prevalent in Japan. Furthermore, the potential application of CCR4 CAR-T cell therapy to solid cancers will also be pursued.

1.3. Licensing agreement: IDT & SeQure Dx

Integrated DNA Technologies (IDT; IA, USA; https://eu.idtdna.com), a CRISPR genome editing solutions company, inked a licensing agreement with SeQure Dx (MA, USA; www.sequre-dx.com), a company focused on off-target analysis for preclinical and clinical gene modification customers, bolstering IDT's complete CRISPR portfolio comprised of world-class research use only to cGMP solutions from design to analysis [3]. The licensing agreement enables IDT to support cell and gene therapy developers through all phases of their CRISPR-based therapeutic programs by providing comprehensive off-target analysis services, powered by SeQure Dx's GUIDE-seq technology, alongside IDT's rhAmpSeq™ CRISPR Analysis System.

1.4. Licensing agreement: pluristyx & humacyte

Pluristyx (WA, USA; https://pluristyx.com), a provider of tools, technologies, and services for the development of cellular therapies, has announced a license agreement with Humacyte (NC, USA; https://humacyte.com), a clinical-stage biotechnology platform company developing universally implantable, bioengineered human tissue at commercial scale [4]. Humacyte has licensed Pluristyx's clinical-grade PluriBank™ induced Pluripotent Stem Cell (iPSC) line as starting materials for manufacturing insulin-producing cells for their BioVascular Pancreas (BVP™) product candidate. This partnership includes access to Pluristyx's revolutionary panCELLa™ platform that enables the generation of “hypoimmune” cells for clinical implantation. PluriBank™ iPSCs are derived from regulatory-compliant donors, extensively characterized, and expanded and banked to provide purity, identity, and genetic integrity for patient safety, available with custom edits and Pluristyx's proprietary FailSafe® and iACT™ edits with a goal of providing improved safety and efficacy. The combination of Humacyte's Acellular Tissue Engineered Vessel (ATEV™) with insulin-producing cells derived from Pluristyx's best-in-class iPSC lines could brings us one step closer to curing insulin dependent diabetes.

1.5. Licensing agreement: XyloCor & SmartCella

XyloCor Therapeutics (PA, USA; www.xylocor.com), a clinical-stage biopharmaceutical company developing novel gene therapies for cardiovascular disease, and SmartWise, a unit of SmartCella Holding (Sweden; www.smartcella.com), have entered into a licensing agreement under which XyloCor has rights to the Extroducer® Infusion Catheter System®, a first-in-class endovascular device designed to deliver advanced therapies directly into the heart and hard-to-reach tissues [5]. XyloCor plans to deploy the Extroducer to support catheter-based endocardial delivery of its lead gene therapy candidate, XC001 (encoberminogene rezmadenovec), in future clinical studies and commercial use.

XC001 is designed to reduce ischemic burden by creating new blood vessels in the heart through the local expression of multiple isoforms of VEGF. With the use of the Extroducer catheter, XyloCor can offer patients a better delivery option for local administration of XC001 directly to the heart, that is less invasive and eliminates potential risks associated with surgical administration.

2. Achievements, launches…

2.1. bit.bio

bit.bio (UK; www.bit.bio), the company coding human cells for novel cures, has launched a panel of 16 new human iPSC-derived models for neurodegenerative diseases such as Alzheimer's and Parkinson's disease [6].

The disease models have been generated by engineering disease-related mutations into one of three existing CNS ioWild Type Cells™ in bit.bio's portfolio - ioGlutamatergic Neurons™, ioGABAergic Neurons™ and ioMicroglia™. bit.bio now offers more than 30 human cell products for neurodegenerative disease within its ioCells™ portfolio, including ioWild Type Cells, ioDisease Model Cells™ and ioCRISPR-Ready CellsTM.

2.2. One80

One80 Intermediaries (MA, USA; www.one80.com), a specialty insurance broker, has announced the launch of GeneBridge, an innovative product created to mitigate the financial impact of high-cost gene therapy claims [7].

GeneBridge is a reinsurance facility designed for blocks of business including employer stop loss programs and health plans. Programs that purchase GeneBridge are reimbursed up to a scheduled amount for the list price and administration of the FDA-approved therapies.

More than 10,000 diseases are linked to genetic disorders fueling a rapid growth in approved treatments. At an average cost per therapy of over US$2.5 million, related high-cost claims are expected to grow at an equally rapid pace.

2.3. STEMCELL technologies

STEMCELL Technologies (BC, Canada; www.stemcell.com) has commercially launched the CellPore™ Transfection System, providing a new technology with the potential to advance cell engineering research and the development of novel cell therapies to cure diseases [8].

The CellPore Transfection System represents a substantial leap forward for cell engineering researchers, offering a novel method—known as mechanoporation—for cargo delivery into mammalian cells. Unlike traditional electroporation techniques, the CellPore Transfection System squeezes cells to create temporary pores in the cell membrane through which the cargo is introduced.

In 2022, STEMCELL announced a collaboration with SQZ Biotechnologies, followed by the acquisition of substantially all of the company's assets in February 2024, including its entire portfolio of over 400 patents and trademarks, and other intellectual property such as copyrights and trade secrets. STEMCELL then successfully leveraged SQZ's Cell Squeeze® technology and intellectual property to commercialize and launch the CellPore Transfection System.

The CellPore platform, designed for Research Use Only applications, includes the benchtop CellPore Transfection System and the CellPore Transfection Kit 300 that features a specialized reagent kit and single-use delivery cartridges.

3. Clinical trials

3.1. Pluripotent stem cells

3.1.1. Heartseed

Heartseed (Japan; https://heartseed.jp/en/) has announced that the Safety Monitoring Committee (SMC) has completed its review of the low-dose patient cohort in the Phase I/II clinical trial (LAPiS Study) for HS-001, an allogeneic iPSC-derived cardiomyocyte spheroid product for advanced heart failure due to ischemic heart disease [9,10]. The trial will now enrol the high-dose cohort of 150 million cardiomyocytes.

The ongoing Phase I/II LAPiS trial is designed to evaluate the safety and tolerability of HS-001 in patients with advanced heart failure. The administration to five patients in the low-dose (50 million cardiomyocytes each) cohort was completed in May 2024. No dose-limiting toxicities or safety concerns affecting the continuation of the trial have been observed. Heartseed plans to start the high-dose administration to continue the clinical evaluation of HS-001.

3.2. Immune cells

3.2.1. J&J

Johnson & Johnson (NJ, USA; www.jnj.com) has announced positive results from a prespecified second interim analysis of the Phase 3 CARTITUDE-4 study evaluating CARVYKTI® (ciltacabtagene autoleucel; cilta-cel) compared with standard therapies of pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd) for the treatment of patients with relapsed or lenalidomide-refractory multiple myeloma after one prior line of therapy [11,12]. The interim analysis showed a statistically significant and clinically meaningful improvement in overall survival for patients treated with CARVYKTI versus standard therapies. Safety data were consistent with the approved label.

CARVYKTI is a BCMA-directed, genetically modified autologous T-cell immunotherapy, which involves reprogramming a patient's own T-cells with a transgene encoding CAR that directs the CAR-positive T cells to eliminate cells that express BCMA. BCMA is primarily expressed on the surface of malignant multiple myeloma B-lineage cells, as well as late-stage B cells and plasma cells. The CARVYKTI CAR protein features two BCMA-targeting single domains designed to confer high avidity against human BCMA. Upon binding to BCMA-expressing cells, the CAR promotes T-cell activation, expansion, and elimination of target cells.

4. Regulations, approvals, acquisitions…

4.1. Acquisitions

4.1.1. Illumina & fluent

llumina (CA, USA: www.illumina.com), a company focused on DNA sequencing and array-based technologies, has acquired Fluent BioSciences (MA, USA; www.fluentbio.com), developer of an emerging and highly differentiated single-cell technology [13]. Fluent's novel approach relies on Pre-Templated Instant Partitions (PIPs) to simultaneously segregate complex cell mixtures into partitions with barcoded template particles that can be easily processed for single cell applications such as single cell RNA sequencing (scRNA-Seq). This approach (PIPseq™) eliminates the need for complex, expensive instrumentation and microfluidic consumables.

4.2. Green light

4.2.1. Adicet

Adicet Bio (CA, USA; www.adicetbio.com), a clinical stage biotechnology company discovering and developing allogeneic gamma delta T cell therapies for autoimmune diseases and cancer, has announced the US FDA has granted Fast Track Designation to ADI-270 for the potential treatment of patients with metastatic/advanced clear cell renal cell carcinoma who have been treated with an immune checkpoint inhibitor and a vascular endothelial growth factor inhibitor [14].

ADI-270 is an armored allogeneic “off-the-shelf” gamma delta CAR T cell therapy candidate targeting CD70-positive cancers. CD70 is a compelling target due to its high expression in both solid and hematological malignancies. ADI-270 is engineered with a third-generation CAR designed to target CD70 using its natural receptor, CD27, as the binding moiety and is further armored with a dominant negative form of TGFBR II to provide functional resilience to the immunosuppressive tumor microenvironment. ADI-270 is also designed to increase exposure and persistence by reducing susceptibility to host vs. graft elimination. These properties of ADI-270 combined with the potent tumor infiltration demonstrated with γδ 1 T cells aim to improve clinical responses of RCC patients and other patients with CD70⁺ tumors.

4.2.2. AffyImmune

AffyImmune (MA, USA; https://affyimmune.com), a clinical-stage biotechnology company committed to developing novel, first-in-class CAR T cell therapies, announced the designation of Regenerative Medicine Advanced Therapy (RMAT) by the US FDA for its CAR T-cell product candidate, AIC100 as a potential treatment for patients with recurrent anaplastic thyroid cancer, the most aggressive form of the disease [15,16].

AIC100 is an ICAM-1 targeting and affinity-tuned LFA-1 binder CAR T-cell therapy.

4.2.3. Anixa biosciences

Anixa Biosciences (CA, USA; www.anixa.com), a biotechnology company focused on the treatment and prevention of cancer, today announced that its collaborator, Moffitt Cancer Center (Moffitt), has received approval by the US FDA of an individual patient Investigational New Drug Application (IND) to allow a second dose of its CAR-T therapy for a patient that may be demonstrating clinical activity to the initial treatment [17,18].

The approach is based on targeting FSHR, which is only expressed on ovary cells in a healthy adult female. The purpose of the first in human study is to evaluate the safety of treatment with autologous T cells genetically modified to express a chimeric endocrine receptor (CER) targeting the FSHR (FSHCER T cells), with or without conditioning chemotherapy, in participants with recurrent or persistent ovarian, fallopian tube, or primary peritoneal cancer.

4.2.4. BioSyngen

Biosyngen (Singapore; www.biosyngen.com), a biotechnology company focused on the development of innovative cell therapies, recently announced that the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) in China has approved the initiation of a pivotal Phase ll clinical trial evaluating BRG01, the company's autologous Epstein-Barr virus (EBV) specific CAR T-cell therapy, for the treatment of patients with recurrent or metastatic EBV-positive nasopharyngeal carcinoma [19].

BRG01 is an autologous T cell immunotherapy product that has been engineered to express chimeric receptors targeting the EBV antigen on the surface of T cells. This innovative therapy represents a new generation of CAR-T cell treatment specifically designed to target EBV. BRG01 received phase I clinical trial approval from the CDE in China in December 2022 and from the US FDA in February 2023 [20]. Subsequently, it was granted Orphan Drug Designation and Fast Track Designation by the FDA in June and July 2023, respectively. BRG01 is the world's first CAR-T therapy for solid tumor to obtain clinical trial approvals from China and the USA and to advance to a pivotal Phase ll clinical trial, representing a significant milestone in the field of cell-based immuno-therapies for solid cancers.

4.2.5. Diakonos

Diakonos Oncology (TX, USA; www.diakonosoncology.com), a clinical stage immuno-oncology company, announced that the US FDA has granted Fast Track Designation for the company's unique dendritic cell vaccine (DCV) for pancreatic ductal adenocarcinoma [21]. The company's DCVs are made with a patient's dendritic cells and a sample of their tumor. These highly differentiated double-loaded dendritic cell vaccines activate robust cytotoxic TH1 cell signaling pathways that initiate a natural immune response to target and eliminate cancer cells. This is achieved without any genetic modification of the patient's immune cells, which greatly simplifies the manufacturing process and significantly reduces costs when compared with leading cell therapy approaches.

4.2.6. IASO bio

IASO Biotechnology (China; www.iasobio.com), a biopharmaceutical company dedicated to discovering, developing, manufacturing and commercializing innovative cell therapy and antibody products, has announced that the IND application for the independently developed fully human anti-BCMA chimeric antigen receptor autologous T cell injection (Equecabtagene Autoleucel, Eque-cel) has been approved by the US FDA for the treatment of multiple sclerosis [22]. This is the second FDA IND approval of Eque-cel for the treatment of autoimmune diseases in 2024, following refractory generalized myasthenia gravis.

4.2.7. Interius

Interius BioTherapeutics (PA, USA; https://interiusbio.com), a leading developer of in vivo cell-specific gene medicines, has been granted Human Research Ethics Committee (HREC) approval and Clinical Trial Notification (CTN) clearance by the Australian Therapeutic Goods Administration (TGA) to commence a first-in-human Phase 1 clinical trial of INT2104, its lead in vivo CAR candidate for treatment of B-cell malignancies [23,24].

INT2104 is a wholly owned investigational gene therapy candidate, which specifically targets CD7-positive T and NK cells and delivers a CAR transgene to create effector CAR-T and CAR-NK cells in vivo. The CAR cells target CD20-positive B cells for the treatment of B cell malignancies. Unlike ex vivo CAR-T therapies, INT2104 is an off-the-shelf, single dose treatment, administered systemically through intravenous infusion without the need for lymphodepletion or for any special equipment or training.

4.2.8. Myogenica

Myogenica (MN, USA; www.myogenica.com), has announced US FDA approval for an Investigational New Drug (IND) application for MyoPAXon — an iPSC-derived muscle stem cell product to regenerate skeletal muscle. A pending clinical trial would evaluate the safety, tolerability and engraftment of MyoPAXon in patients with Duchenne muscular dystrophy [25].

4.2.9. Obsidian

Obsidian Therapeutics (MA, USA; https://obsidiantx.com), a clinical-stage biotechnology company pioneering engineered cell and gene therapies, has announced that the US FDA has granted Fast Track Designation to OBX-115, a novel engineered tumor-derived autologous T cell immunotherapy (tumor-infiltrating lymphocyte [TIL] cell therapy) armored with pharmacologically regulatable membrane-bound IL15 (mbIL15), for the treatment of patients with metastatic or locally advanced melanoma that is refractory to or has relapsed after PD-1/PD-L1–based immune checkpoint inhibitors [26].

OBX-115 is being investigated in a multicenter trial in advanced or metastatic melanoma and non-small cell lung cancer [27]. Enrollment has been completed for the first-in-human, single-center study of OBX-115 in adult patients with metastatic melanoma [28].

4.2.10. Paradromics

Paradromics (TX, USA; www.paradromics.com), a developer of brain-computer interfaces (BCI), has announced its acceptance into the US FDA's newest program for innovative devices, the Total Product Life Cycle Advisory Program [29,30]. According to the FDA, the TAP accelerator program was launched to “help spur more rapid development and more rapid and widespread patient access to safe, effective, high-quality medical devices of public health importance.”

The TAP program was created exclusively for devices designated by the FDA as Breakthrough Devices. The Paradromics Connexus® Direct Data Interface has received two such designations from the FDA: one recognizing its potential to help patients communicate again after losing the ability to speak and a second for its ability to help patients with severe loss of movement to control computer devices. The FDA Breakthrough Device Designations provide an expedited review process for transformative medical devices with the potential to treat irreversible, debilitating conditions. TAP further accelerates the review process by providing additional opportunities for rapid communication between regulators and companies.

4.2.11. SCG cell therapy

SCG Cell Therapy (Singapore; www.scgcell.com) a biotechnology company developing novel immunotherapies for infectious diseases and their associated cancers, has announced that US FDA has approved the IND application to initiate Phase 1/2 clinical trial for SCG142, a novel next-generation human papillomavirus (HPV) E7-specific T-cell receptor-engineered T (TCR T) cell therapy for patients with HPV-associated solid tumors [31,32].

SCG142 is a high-avidity fully natural HPV-specific TCR armored with a TGFBRII-41BB chimeric switch receptor.

4.2.12. Umoja

Umoja Biopharma (WA, USA; www.umoja-biopharma.com), a transformative immunotherapy company creating off-the-shelf treatments that aim to extend the reach and effectiveness of CAR-T cell therapies in oncology and autoimmunity, has announced the clearance of its IND application by the US FDA for UB-VV111, a gene therapy that generates CD19 CAR T-cells in situ, intended to treat hematologic malignancies [33]. Umoja expects to initiate a Phase 1 study and dose the first patient in the trial by the end of 2024. UB-VV111 is the first asset from the VivoVec™ gene delivery platform to enter the clinic.

Umoja's VivoVecTM gene delivery platform combines third generation lentiviral vector gene delivery with a novel T cell targeting and activation surface complex. This enables T cells in the body to manufacture their own cancer-fighting CAR-T cells in vivo. This has the potential to eliminate many challenges associated with traditional CAR-T approaches, including reliance on gathering a patient's own or donor cells which are modified externally before being delivered back to the patient, the associated time lag and manufacturing challenges of ex vivo cell modification, and the need for patient's lymphodepletion.

UB-VV111 is a lentiviral vector-based gene therapy from Umoja's VivoVec platform, comprising a surface-engineered viral envelope. UB-VV111 encodes a transgene for an anti-CD19 CAR and a RACRTM, which is designed to enrich and expand UB- VV111 engineered CAR T cells in vivo. UB-VV111 is being investigated in a range of B-cell malignancies including Large B-Cell Lymphoma and Chronic Lymphocytic Leukemia.

The Phase 1 study for UB-VV111 will be a dose escalation and confirmation study designed to evaluate the safety, tolerability, and clinical antitumor activity of UB-VV111. The study will enroll subjects in relapsed/refractory large-B-cell lymphoma (LBCL) and chronic lymphocytic leukemia (CLL) in both CAR T naive and CAR T treated patients.

5. Capital Market & Finances

5.1. Aspect

Aspect Biosystems (BC, Canada; www.aspectbiosystems.com), a biotechnology company developing bioprinted tissue therapeutics, has received a CA$72.75 (US$53.85 M) investment from the Governments of Canada and British Columbia [34].

The investment will support a CA$200 (US$148.0) M, multi-year project to advance Aspect's unique clinical biomanufacturing capabilities, full-stack tissue therapeutic platform, and pipeline of bioprinted tissue therapeutics. These next generation therapeutics are designed to replace, repair, or supplement biological functions in the body with the aim of delivering a new class of truly disease-modifying treatments and functional cures for some of the most elusive diseases.

This project will leverage Aspect's landmark partnership with global healthcare leader Novo Nordisk in diabetes and obesity as well as accelerate Aspect's own internal therapeutic pipeline for other serious metabolic and endocrine diseases, including liver disease.

Financial disclosure

The author D Ilic has received an honorarium from Taylor & Francis for the contribution of this work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.