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

TWEETABLE ABSTRACT

Regenerative medicine industry news digest, February 2024.

Keywords: :

• clinical trial
• gene therapy
• industry
• policy
• regeneration
• regulation
• stem cells

1. Business development

1.1 Co-development agreement: Astellas & Kelonia

Astellas Pharma (Japan; www.astellas.com) and Kelonia Therapeutics (MA, USA; https://keloniatx.com) have announced that Xyphos Biosciences (CA, USA; https://xyphosinc.com), a wholly owned subsidiary of Astellas, and Kelonia have entered into a research collaboration and license agreement to develop novel Immuno-Oncology therapeutics [1].

Kelonia is a biotech company pioneering a new wave of genetic medicines using its in vivo gene placement system (iGPS^®). iGPS^® uses next-generation lentiviral particles to efficiently deliver genetic cargo precisely to the desired target cells inside the patient's body. Xyphos holds a novel and proprietary ACCEL™ technology platform that uses its convertible Chimeric Antigen Receptor (convertibleCAR^®) on immune cells.

Under the terms of the agreement, the companies plan to combine Kelonia's iGPS with Xyphos' ACCEL technology to develop innovative in vivo CAR-T Cell therapies targeting up to two programs. Xyphos will be responsible for the development and commercialization of products created from the collaborative research. Kelonia will receive US $40 million upfront for the first program, and an additional US $35 million should Xyphos exercise its options for the second program, and potential milestones and contingency payments approaching US $800 million in total. Additionally, Kelonia will receive R&D funding for work performed in the collaboration and is eligible for tiered royalties on net sales up to the double-digit percentage.

1.2. Collaboration agreement: ATCC & Tissue Dynamics

ATCC (VA, USA; www.atcc.org), biological materials management and standards organization, and Tissue Dynamics (Israel; www.tissuedynamics.com), a pharma-tech company integrating advanced artificial intelligence tools with bionic human organoids, have announced a partnership to develop workflow-friendly cardiac organoids-based kits for improved cardiac safety testing in drug development [2].

1.3. Collaboration agreement: BioNTec & Autolus

BioNTech (Germany; www.biontech.com), a next-generation immunotherapy company pioneering novel therapies for cancer and other serious diseases, and Autolus Therapeutics (UK; www.autolus.com), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, have announced a strategic collaboration aimed at advancing both companies' autologous CAR-T programs toward commercialization, pending regulatory authorizations [3]. In connection with the strategic collaboration, the companies entered into a license and option agreement and a securities purchase agreement. BioNTech has agreed to purchase US $200 million of Autolus' American Depositary Shares in a private placement. BioNTech will have a right to appoint a director to the Board of Autolus.

Under the terms of the license and option agreement, BioNTech will make a cash payment of US $50 million and is granted among other right also the following:

• BioNTech has the option to access Autolus' commercial and clinical site network, manufacturing capacities in the United Kingdom and commercial supply infrastructure in a cost-efficient set-up in order to accelerate the development of BNT211 in additional CLDN6+ tumor types. BioNTech plans to have 10 or more ongoing potentially registrational clinical trials in the pipeline by the end of 2024, including its fully owned CLDN6 CAR-T program BNT211 in relapsed or refractory germ cell tumors.

• Autolus will lead the development and commercialization for their programmed T cell therapies AUTO1/22, targeting CD19 and CD22, and AUTO6NG, targeting GD2, in any oncology indication with BioNTech having an option to support certain development activities and co-commercialize both candidates in certain territories.

• Autolus granted BioNTech an exclusive license to develop and commercialize therapeutics incorporating certain of Autolus' proprietary binders along with options to license binders and cell programming technology for use in BioNTech's in vivo cell therapy development programs and investigational antibody-drug conjugates.

1.4. Distribution agreement: Charles River & Pluristyx

Charles River Laboratories International (MA, USA; www.criver.com) has entered into an agreement with Pluristyx (WA, USA; https://pluryistyx.com) a provider of tools, technologies, and services for the development of cell therapies [4]. Under the terms of the agreement, Charles River will distribute a broad catalogue of Pluristyx's human embryonic and induced pluripotent stem cell (hESC/iPSC) lines for research use and will exclusively offer specific pluripotent stem cell lines derived under Good Tissue Practice to support a path to the clinic.

2. Achievements, launches…

2.1. AstraZeneca

AstraZeneca (UK; www.astrazeneca.com) is investing US $300 million in a state-of-the-art facility in Rockville, MD, USA, to launch its life-saving cell therapy platforms in the US for critical cancer trials and future commercial supply [5]. More than 150 new highly skilled jobs will be created to initially focus on manufacturing T-cell therapies to enable clinical trials to be conducted around the world. Over time, the site may expand its focus to support other disease areas. The site represents the latest investment in cell therapy for AstraZeneca.

2.2. Gemini

Gemini Bioproducts (CA, USA; www.geminibio.com), a supplier of cell culture reagents and process liquids, has launched a new human AB serum product for the cell therapy and regenerative medicine markets [6]. To meet specific regulatory requirements, including requirements within the USA and the EU, the source plasma is collected from a maximum of 16 healthy male donors of the AB serotype. The donor material must also pass extensive viral testing requirements, and the manufacturing process includes defibrination of the source AB plasma using therapeutic grade recombinant human thrombin. GeminiBio manufactures all human serum products under cGMP.

3. Clinical trials

3.1. Immune cells

3.1.1. Aleta

Aleta Biotherapeutics (MA, USA; www.aletabio.com), a clinical stage, immuno-oncology company with a CAR T-Cell Engager (CTE) platform that enables cell cancer therapies to work more effectively, and Cancer Research UK's Centre for Drug Development, have announced that the first patient was dosed in a Phase I/2 clinical trial [7,8]. This trial is evaluating the Company's first-in-class biologic CAR T-Cell Engager, ALETA-001, for the treatment of patients with B-cell malignancies who are relapsed/refractory to CD19-targeting CAR T-cell therapy. ALETA-001, was designed specifically for the treatment of B-cell malignancies in patients who have received a CD19-directed CAR T-cell therapy and are at risk of treatment failure. Developed to improve the effectiveness of CD19-directed CAR T-cell therapies by increasing CD19 antigen density and restoring lost CD19 expression on the cancer cell, ALETA-001 contains the CD19 target protein, which is further linked to an CD20 antibody domain. This allows CD19⁺/CD20⁺ cancer cells to be easily recognized and killed by CD19-directed CAR T-cells that were previously administered and are already circulating within a patient.

3.1.2. Anixa

Anixa Biosciences (CA, USA; www.anixa.com), a clinical-stage biotechnology company focused on the treatment and prevention of cancer, has commenced for the first patient enrolled in the second cohort in the ongoing Phase I clinical trial of its novel CAR T cell therapy for ovarian cancer [9,10].

The first-in-human trial is enrolling patients with recurrent/resistant ovarian cancer who have progressed on at least two prior therapies. The CAR T was safe and tolerable in the first three patients treated. The first patient enrolled in the second cohort received triple the dose of CAR-T cells compared with the dose of the first cohort of three patients. Anixa's FSHR-mediated CAR-T technology, also known as chimeric endocrine receptor T cell (CER T), differs from traditional CAR T therapy by targeting FSHR, which research indicates is expressed on ovarian cells, as well as in the vasculature of tumors.

3.1.3. AvenCell

AvenCell Therapeutics (MA, USA; https://avencell.com) a clinical-stage cell therapy company focused on advancing both autologous and allogeneic switchable CAR-T cell therapies, has dosed the first patient in a Phase IA study with AVC-201 for the treatment of relapsed/refractory Acute Myeloid Leukemia and other selected hematologic malignancies positive for CD123 [11,12]. AVC-201 is a CRISPR-edited CAR T Cell therapy that embodies two discrete technology platforms. The first leverages AvenCell's ‘UniCAR’ universal/switchable technology, which is comprised of a two-component system. Engineered T Cells are transduced with a ‘universal’ receptor that is completely biologically inert (expressing human La peptide) and are only activated when bound to a second biologic molecule (‘targeting module’) which directs the T cells to a cancer antigen of interest, which in this case is CD123. The presence or absence of the targeting module in circulation allows for exquisite ‘on’ and ‘off’ control, respectively, of the therapeutic activity. The second technology platform consists of an in-licensed allogeneic cell engineering technology developed by Intellia Therapeutics (MA, USA; www.intelliatx.com), which allows for unrelated donors to provide cells for patients. These cells are uniquely engineered via CRISPR/Cas9 to avoid graft versus host disease and rejection via the host/patient immune system by either innate or adaptive mechanisms.

3.1.4. Triumvira

Triumvira Immunologics (TX; USA; https://triumvira.com), a clinical-stage company developing novel, targeted autologous and allogeneic T-cell therapeutics that co-opt the natural biology of T cells to treat patients with solid tumors, has announced that the first patient was dosed in its TACTIC-3 trial, a Phase I/II study, investigating the safety and efficacy of autologous TAC-T cell asset, TAC101-CLDN18.2, targeting Claudin 18.2+ solid tumors [13,14]. TAC101-CLDN18.2 is a novel cell therapy based on genetically engineered autologous T cells expressing a T-cell Antigen Coupler that harnesses the inherent signaling pathways of the native T cell receptor complex and targets Claudin 18.2, an epithelial transmembrane protein overexpressed in gastric cancer and several other solid tumor types.

4. Regulations, approvals, acquisitions…

4.1. Green light

4.1.1. Artiva

Artiva Biotherapeutics (CA, USA; www.artivabio.com), a clinical stage company whose mission is to deliver highly effective, off-the-shelf, allogeneic natural killer (NK) cell-based therapies, has announced that the US FDA has granted Fast Track designation to Artiva's lead program AlloNK^® for the treatment of lupus nephritis in combination with anti-CD20 antibodies, rituximab or obinutuzumab [15]. AlloNK, also known as AB-101, is an allogeneic NK cell therapy candidate designed to enhance the antibody-dependent cellular cytotoxicity effect of monoclonal antibodies or NK cell engagers.

4.1.2. Biosyngen

Biosyngen (Singapore; www.biosyngen.com), has announced that US FDA granted Fast Track Designation for BST02 for the treatment of all types of liver cancer, including hepatocellular carcinoma and cholangiocarcinoma. BST02, a T cell therapy based on the expansion of the patient's own tumor infiltrating lymphocytes, falls within the category of adoptive immune cell therapy technology [16].

4.1.3. Bone Solutions

Bone Solutions (TX, USA; www.bonesolutions.net), an orthobiologics technology company, has announced 510(k) clearance of Mg OSTEOCRETE from the US FDA for use in the intervertebral body disc space, including cervical, thoracic and lumbar fusion procedures [17]. This marks the first and only magnesium-based bone substitute to be cleared by the FDA for this application.

The magnesium component of Mg OSTEOCRETE is the significant differentiator from other bone substitutes on the market. The crystallization reaction from magnesium oxide and the blend of phosphate-based materials allows for ideal osteoconductivity of the product. As a result, post-placement Mg OSTEOCRETE sets and cures in situ without migration. The material stimulates cell adhesion, proliferation, and formation of the bone extracellular matrix by the osteoblasts, promoting bone growth.

4.1.4. Indapta

Indapta Therapeutics (TX, USA; https://indapta.com), a privately held biotechnology company developing next-generation differentiated cell therapies for the treatment of cancer and other immune-mediated diseases, has announced that the US FDA granted Fast Track designation for its lead clinical program, IDP-023, for the treatment of patients with non-Hodgkin's lymphoma and multiple myeloma [18,19].

Indapta's universal, allogeneic NK cell therapy platform consists of a potent subset of naturally occurring NK cells, known as ‘G minus’ NK cells, or ‘g-NK’ that have markedly greater killing capacity than conventional NK cells, without the need for genetically engineering the cells. G-NK cells arise from epigenetic changes resulting from exposure to cytomegalovirus (CMV). To generate IDP-023, Indapta preferentially expands g-NK cells from healthy donors with increased numbers of g-NK cells, with low donor-to-donor variability. Indapta's g-NK are capable of releasing dramatically more immune activating cytokines and cancer-killing compounds than conventional NK cells.

Patients being enrolled now in Indapta's phase I clinical trial are receiving up to three planned doses of IDP-023 with or without IL-2. Once safety of multiple doses in combination with IL-2 has been established, cohorts of patients with lymphoma and multiple myeloma will receive treatment with IDP-023 in combination with the monoclonal antibodies, rituximab and daratumumab, respectively.

4.1.5. Iovance

Iovance Biotherapeutics (CA, USA; www.iovance.com), a biotechnology company focused on innovating, developing, and delivering novel polyclonal tumor infiltrating lymphocyte (TIL) cell therapies for patients with cancer, has announced that the US FDA has approved AMTAGVI™ (lifileucel) suspension for intravenous infusion [20,21]. AMTAGVI is a tumor-derived autologous T cell immunotherapy indicated for the treatment of adult patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor with or without an MEK inhibitor. This indication is approved under an accelerated approval based on overall response rate and duration of response. Iovance is also conducting TILVANCE-301, a phase III trial to confirm clinical benefit.

AMTAGVI is the first and the only one-time, individualized T-cell therapy to receive FDA approval for a solid tumor cancer. The proposed mechanism for AMTAGVI offers a new cell therapy approach that deploys patient-specific T cells called TIL cells. When cancer is detected, the immune system creates TIL cells to locate, attack, and destroy cancer. TIL cells recognize distinctive tumor markers on the cell surface of each person's cancer. When cancer develops and prevails, the body's natural TIL cells can no longer perform their intended function to fight cancer.

AMTAGVI is manufactured using a proprietary process to collect and expand a patient's unique T cells from a portion of their tumor. AMTAGVI returns billions of the patient's T cells back to the body to fight their cancer. Authorized Treatment Centers will administer AMTAGVI to patients as part of a treatment regimen that includes lymphodepletion and a short course of high-dose PROLEUKIN^® (aldesleukin).

4.1.6. Lineage Cell Therapeutics

Lineage Cell Therapeutics (CA, USA; http://lineagecell.com), a clinical-stage biotechnology company developing allogeneic cell therapies for unmet medical needs, has announced the clearance, by the US FDA, of its Investigational New Drug amendment (INDa) for OPC1, an investigational allogeneic oligodendrocyte progenitor cell transplant for the treatment of spinal cord injury (SCI) [22]. Pursuant to the INDa, Lineage has initiated activities to open its first clinical site in the DOSED (Delivery of Oligodendrocyte Progenitor Cells for SCI: Evaluation of a Novel Device) study to evaluate the safety and utility of a novel spinal cord delivery device in subacute and chronic SCI patients. Initial site opening is expected to occur in the second quarter of 2024, following customary trial preparations and submission in the first quarter of a grant application to the California Institute for Regenerative Medicine (CIRM; CA, USA; www.cirm.ca.gov) for potential partial financial support of the DOSED clinical study.

The DOSED clinical study is an open-label, multi-center, device safety study, in approximately three to five subacute and three to five stable chronic subjects with complete (ASIA Impairment Scale A) or incomplete (ASIA Impairment Scale B), traumatic, focal SCI affecting either cervical (C4-C7) or thoracic (T1-T10) vertebrae. The primary objective of this study is to evaluate the safety of a novel spinal cord delivery device to administer OPC1 to the spinal parenchyma. The primary end point is safety, as measured by the frequency and severity of adverse events through 30 days following OPC1 injection that are related to the injection procedure. Secondary end points are safety and tolerability, as measured by the frequency and severity of adverse events, including adverse events of special interest, through 90 days following OPC1 injection, that are related to OPC1 and/or the concomitant short-term immunosuppression.

4.1.7. Vertex

Vertex Pharmaceuticals (MA, USA; www.vrtx.com) has announced that the European Commission has granted conditional marketing authorization to CASGEVY™ (exagamglogene autotemcel [exa-cel]), a CRISPR/Cas9 gene-edited therapy [23]. CASGEVY is approved for the treatment of patients who are 12 years of age and older with severe sickle cell disease (SCD) characterized by recurrent vaso-occlusive crises or transfusion-dependent beta thalassemia (TDT), for whom hematopoietic stem cell transplantation is appropriate and a human leukocyte antigen matched related donor is not available. CASGEVY is the only genetic therapy approved for SCD and TDT patients in the EU and with this approval, there are now more than 8000 patients potentially eligible for treatment.

CASGEVY™ is a non-viral, ex vivo CRISPR/Cas9 gene-edited cell therapy for eligible patients with SCD or TDT, in which a patient's own hematopoietic stem and progenitor cells are edited at the erythroid specific enhancer region of the BCL11A gene through a precise double-strand break. This edit results in the production of high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is the form of the oxygen-carrying hemoglobin that is naturally present during fetal development, which then switches to the adult form of hemoglobin after birth.

5. Acquisitions, mergers…

5.1. Kadimastem & IMC

IM Cannabis (IMC; ON, Canada; https://imcannabis.com), a medical cannabis company with operations in Israel and Germany, is has entered into a non-binding term sheet dated and a Loan Agreement with Kadimastem (Israel; www.kadimastem.com), a clinical cell therapy public company working on development of pluripotent stem cell-based therapies, whereby the parties will complete a business combination that will constitute a reverse merger into the company by Kadimastem [24].

5.2. STEMCELL Technologies & SQZ

STEMCELL Technologies (Canada; www.stemcell.com) has announced the acquisition of substantially all assets of SQZ Biotechnologies (MA, USA; https://sqzbiotech.com) company known for its method of introducing a variety of therapeutic cargo into cells by squeezing them (mechanoporation) rather than using electricity (electroporation) [25]. STEMCELL has acquired all SQZ's assets including its entire portfolio of over 400 patents and trademarks, other intellectual property such as copyrights and trade secrets, proprietary equipment, and its head license with the Massachusetts Institute of Technology.

6. Capital market & finances

6.1. CIRM

The California Institute for Regenerative Medicine (CIRM; CA, USA; www.cirm.ca.gov), the world's largest institution dedicated to regenerative medicine, awarded US $56 million to support seven projects in the Agency's clinical program which provides funding for eligible stem cell and gene therapy-based projects through all stages of clinical trial development [26]. Awardees include Aspen Neuroscience (CA, USA; https://aspenneuroscience.com) for a Phase I/2a dose escalation study of autologous neuron replacement in sporadic Parkinson's disease, ImmPACT-Bio (CA, USA; https://immpact-bio.com) for a phase I/II study to evaluate a bi-specific CD19/CD20-directed CAR T-cell, in refractory lupus nephritis and systemic lupus erythematosus, and Fate Therapeutics (CA, USA; https://fatetherapeutics.com) for a phase I study in participants with moderate to severe active systemic lupus erythematosus.

In addition, CIRM approved awarding US $21.3 million to create a network of Shared Resources Laboratories for Stem Cell-Based Modeling, an important component of CIRM's Infrastructure Program.

6.2. Kenai

Kenai Therapeutics (CA, USA; www.kenaitx.com), a biotechnology company leveraging induced pluripotent stem cell (iPSC) technology to discover and develop a platform of allogeneic neuron replacement cell therapies for neurological disorders, has announced an US $82 million Series A financing [27]. Kenai Therapeutics previously raised seed funding under the name Ryne Bio. Proceeds from the financing will enable the Company to submit an IND for RNDP-001 and complete phase I clinical trials, which will initiate within the year. RNDP-001 is an iPSC-derived, allogeneic dopamine progenitor cell therapy for the treatment of both idiopathic and inherited forms of Parkinson's disease, and has displayed robust survival, innervation and behavioral rescue in preclinical models of Parkinson's disease.

6.3. Kyverna

Kyverna Therapeutics (CA, USA; www.kyvernatx.com), a clinical-stage biopharmaceutical company focused on developing cell therapies for patients suffering from autoimmune diseases, has its upsized initial public offering of 16,675,000 shares of its common stock, which includes the exercise in full by the underwriters of their option to purchase 2,175,000 additional shares, at an initial public offering price of US $22.00 per share [28].

The aggregate gross proceeds from the offering, before deducting underwriting discounts and commissions and other offering expenses payable by Kyverna, were approximately US $366.9 million. Kyverna's common stock began trading on the Nasdaq Global Select Market on 8 February 2024 under the ticker symbol ‘KYTX’.

6.4. Lineage Cell Therapeutics

Lineage Cell Therapeutics (CA, USA; http://lineagecell.com), a clinical-stage biotechnology company developing allogeneic cell therapies for unmet medical needs, has closed its previously announced registered direct offering for the purchase and sale of 13,461,540 of the company's common shares at an offering price of US $1.04 per common share [29]. The aggregate gross proceeds to Lineage from the offering at the closing were US $14.0 million before deducting estimated offering expenses payable by Lineage. Lineage intends to use the proceeds from the offering for general corporate purposes, which may include clinical trials, research and development activities, general and administrative costs, and to meet working capital needs.

6.5. Neurona

Neurona Therapeutics (CA, USA; www.neuronatherapeutics.com), a clinical stage biotherapeutics company advancing regenerative cell therapy candidates for the treatment of neurological disorders, have announced the successful completion of a US $120 million financing [30]. Proceeds from the financing will be used to advance the company's pipeline of wholly owned, off-the-shelf cell therapies for multiple indications, including its lead investigational candidate, NRTX-1001.

NRTX-1001 is a regenerative neural cell therapy candidate derived from human pluripotent stem cells. The fully differentiated neural cells, called interneurons, secrete the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Delivered as a one-time dose, the human interneurons are intended to integrate on-target and durably silence seizure activity in the epileptic region of the brain. NRTX-1001 is manufactured in Neurona's in-house GMP facility using proprietary methods.

NRTX-1001 is being evaluated in an ongoing open-label, single-arm phase I/II clinical trial for treatment of drug-resistant mesial temporal lobe epilepsy and has potential application in Alzheimer's disease and other disorders of the nervous system [31].

6.6. Tevogen

Tevogen Bio (NJ, USA; https://tevogen.com), a clinical-stage specialty immunotherapy company harnessing one of nature's most powerful immunological weapons, CD8⁺ cytotoxic T lymphocytes, to develop off-the-shelf, genetically unmodified precision T-cell therapies for the treatment of infectious diseases, cancers, and neurological disorders, aiming to address the significant unmet needs of large patient populations, celebrated commencement of its public trading by ringing the opening bell at the Nasdaq Stock Exchange in Times Square, NY, USA, on 15 February 2024 (Nasdaq: TVGN) [32].

Financial disclosure

The author Dusko 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.

Writing disclosure

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

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.