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

1. Business development

1.1. Collaboration agreement: acepodia and Pfizer

Acepodia (CA, USA; www.acepodia.com), a clinical-stage biotechnology company developing first-in-class cell therapies with its unique Antibody-Cell Conjugation (ACC) and allogeneic gamma delta 2 (γδ2) T cell platforms, announced today that it has entered a strategic clinical collaboration with Pfizer Ignite (NY, USA; www.pfizerignite.com) to support the development of its therapies in autoimmune diseases [1]. Pfizer Ignite is an end-to-end offering that leverages Pfizer’s significant resources, scale, and expertise, alongside a proven track record in the development of breakthroughs, to support biotechs seeking to accelerate their innovations from preclinical R&D through the development lifecycle. Under this new agreement, Pfizer Ignite will provide strategic guidance and resources to Acepodia as the company develops its cell therapies for oncology and autoimmune diseases.

Acepodia’s ACC platform, which uses bio-orthogonal chemistry and is based on the pioneering work of 2022 Nobel laureate Dr Carolyn Bertozzi, who applied click chemistry to living systems, creates an off-the-shelf, non-genetically engineered version of CAR-T cell therapy that is more easily scaled and avoids cytokine release storms, neurotoxicity, and other side effects associated with CAR-T cell therapies. Acepodia’s lead clinical candidate, ACE1831, is currently being evaluated in a Phase 1 first-in-human clinical trial for patients with non-Hodgkin’s lymphoma and has demonstrated a robust and durable effect after a single treatment at the lowest dose [2].

With the agreement, Acepodia will retain all rights related to the progress of the program and future partnership opportunities.

1.2. Collaboration agreement: carisma and Moderna

Carisma Therapeutics (PA, USA; https://carismatx.com), a clinical stage biopharmaceutical company focused on discovering and developing innovative immunotherapies, has announced the expansion of its in vivo chimeric antigen receptor macrophage and monocyte (together, “CAR-M”) collaboration with Moderna (MA, USA; www.modernatx.com) to include the nomination of two targets for the treatment of autoimmune diseases [3]. Carisma retains all rights in autoimmune disease beyond the two nominated targets, which will be exclusively partnered with Moderna.

Under this expanded collaboration, Carisma and Moderna will leverage Carisma’s proprietary CAR-M technology and Moderna’s mRNA/LNP platform to develop novel in vivo macrophage engineering approaches in the nominated autoimmune disease targets. Carisma will receive research funding and is eligible to receive development, regulatory, and commercial milestone payments, plus royalties on net sales of any products that are commercialized under the collaboration agreement. Carisma will be responsible for the discovery and optimization of development candidates, while Moderna will lead the clinical development and commercialization of therapeutics resulting from the agreement.

1.3. Collaboration agreement:cellular origins and 3P innovation

Cellular Origins (UK; https://cellularorigins.com), a TTP Company, focused on enabling scalable, cost-effective, and efficient manufacture of cell and gene therapies (CGTs), has announced a collaboration with 3P innovation (UK; www.3pinnovation.com), an engineering company and supplier of automated fill-finish equipment [4]. The partnership will integrate 3P innovation’s cryoFIL™ cryovial filling platform within Cellular Origins’ robotic system, Constellation™, expanding the system’s capabilities by enabling automated filling of cryovials within a closed and sterile environment.

3P innovation’s cryoFIL platform is designed to automate and streamline filling processes in cell and gene therapy workflows, incorporating the Company’s proven technology within a cGMP compliant robotic platform. Designed to provide reliable and repeatable liquid filling, cryoFIL’s automated workflow utilizes a closed loop filling and 100% weight verification approach to ensure the maximum yield of manufactured therapies.

The collaborative partnership will undertake the physical and digital integration of cryoFIL within Constellation, centering around the development of a system for seamless robotic docking with cryoFIL. The integration will allow manufacturing processes that require interfacing with vials and other open format containers to be fully automated, maximizing production efficiencies. This represents an important milestone in the ongoing development of Constellation as an end-to-end automated solution for cell therapy manufacturing. Further expanding the system’s capabilities, the integration of cryoFIL will enable users to alleviate the requirement for manual and problematic process steps in CGT manufacturing that can require significant time and labor investment.

1.4. Licencing agreement: GC cell and Bifarma

GC Cell (South Korea; https://gccell.com/en/main.do), a cell therapy company, has officially announced the execution of a landmark ‘Technology Transfer and License Agreement’ with PT Bifarma Adiluhung (Indonesia; https://bifarma.co.id/), a premier stem cell therapy company in Indonesia [5]. This strategic partnership, which began in June, solidifies approximately three months later with the signing of the final license agreement. Under the terms of the agreement, Bifarma will be granted the exclusive rights to develop, manufacture, and commercialize Immuncell-LC for 15 years.

Bifarma is recognized for operating Indonesia’s first GMP-certified cell therapy production facility and possesses a comprehensive sales and marketing infrastructure focused on oncology, specializing in a cold chain distribution network that spans across Indonesia. This infrastructure is expected to maximize the accessibility and commercial success of Immuncell-LC.

Immuncell-LC, an anti-cancer immune cell therapy, has demonstrated significant efficacy in solid tumors, particularly liver cancer, and has been recognized as an FDA-designated orphan drug. It consists primarily of autologous blood-derived T lymphocytes enhanced to improve cancer cell killing capabilities. The therapy has proven its effectiveness in large-scale Phase 3 clinical trials for early-stage Hepatocellular Carcinoma patients, significantly reducing recurrence risk and mortality with a favorable safety profile.

1.5. Strategic agreement: ossium health and BARDA

Ossium Health (CA, USA; https://ossiumhealth.com), a commercial-stage bioengineering company with the first-of-its-kind bone marrow bank for processing and deploying stem cell-based therapies, has signed a contract with the Biomedical Advanced Research and Development Authority (BARDA; https://aspr.hhs.gov/AboutASPR/ProgramOffices/BARDA/Pages/default.aspx), part of the Administration for Strategic Preparedness and Response within the U.S. Department of Health and Human Services, to advance the company’s ready-to-use bone marrow for national emergency preparedness [6]. The contract, initially funded at US$21 million for its base period, has the potential to reach a total value of US$125 million with additional options spanning five years.

The partnership with BARDA is centered on accelerating the processing of Ossium’s proprietary Hematopoietic Progenitor Cell (HPC) Marrow product, conducting clinical studies to confirm its safety and efficacy, and expanding Ossium’s network of bone marrow banks across the United States. These efforts are part of a broader initiative to prepare for and respond to public health emergencies, specifically those involving radiological or nuclear incidents.

Ossium sources bone marrow from the vertebral bodies of organ donors through its partnerships with 27 Organ Procurement Organizations across the United States. Ossium’s bone marrow, referred to as “HPC, Marrow,” is processed and cryopreserved at Ossium’s production facility in Indianapolis, ensuring that transplantable units are available when patients need them most.

Ossium is currently conducting a clinical study (PRESERVE I) to evaluate the safety and effectiveness of its organ donor-derived bone marrow in patients with hematopoietic malignancies [7]. In parallel, patients globally can access this product through Ossium’s HOPE Program (HPC Offered for PRESERVE Expansion; https://ossiumhealth.com/hope/).

2. Achievements, launches …

2.1. Aurion

Aurio n Biotech (WA, USA; https://aurionbiotech.com), whose mission is to restore vision to millions of patients with life-changing regenerative therapies, has announced the commercial launch of Vyznova® (generic name: neltependocel) in Japan, for the treatment of bullous keratopathy of the cornea [8]. The Company believes this is the first approved cell therapy for the treatment of corneal endothelial disease that has received both regulatory and reimbursement approval in Japan.

Bullous keratopathy is a sight-threatening and debilitating condition affecting the endothelial cells of the cornea. Bullous keratopathy causes the accumulation of water in the form of blisters on the cornea, which can cause severe pain. When the endothelial cells malfunction or die, they are gone for good, since they do not replicate in vivo. The subsequent clouding impairs the transparency of the cornea, and as the condition progresses, vision deteriorates.

Until now, bullous keratopathy has been treated by corneal transplantation using donor corneal tissue. However, the supply of donor corneas has been chronically insufficient. A survey estimates that globally, for every 70 diseased eyes, there is only one donor cornea available for transplant. Lack of corneal tissue in Japan has been a significant challenge in the treatment of bullous keratopathy. By contrast, Aurion Biotech has developed a manufacturing process that can produce up to 1,000 doses from the corneal endothelial cells of a single donor.

2.2. CereVasc

CereVasc (MA, USA; https://cerevasc.com), a clinical-stage medical device company developing novel treatments for neurological diseases, has announced the publication of a study demonstrating that its minimally invasive eShunt® System may help deliver gene therapies to the central nervous system (CNS) [9,10].

In the ovine model study, a standard gene therapy delivery vector – an adeno-associated virus – was successfully distributed to the brain and spinal cord. By targeting the cerebellopontine angle (CPA) cistern at the base of the brain, the location accessible by the eShunt System in ongoing clinical trials for hydrocephalus, the vector ultimately reached a host of key targets within the CNS [11,12]. These results were compared to delivery via cisterna magna, a route of administration that is accompanied by potential risks of serious and possibly fatal complications in patients. The data showed administration to the CPA resulted in comparable rates of biodistribution between the two routes of administration, suggesting that the endovascular CPA approach “could offer a clinically safer and minimally invasive delivery system for CNS gene and cell-based therapies.”

A couple weeks earlier, the Company has announced enrollment of the 50th patient in its pilot studies of the eShunt System in patients with Normal Pressure Hydrocephalus (NPH), in centers in the U.S. and in Argentina [13].

2.3. Emulate

Emulate (MA, USA; https://emulatebio.com), the developer of next-generation in vitro Organ-Chip models, has unveiled the Chip-R1™ Rigid Chip with a minimally drug-absorbing profile to improve biological modeling for ADME (absorption, distribution, metabolism, and excretion) and Toxicology Applications [14]. The chip is designed to minimize drug absorption and enhance biological modeling. Constructed using low-drug-absorbing plastics, Chip-R1 builds upon the core microfluidic design of Organ-Chips, offering researchers greater precision in predicting human drug responses.

Chip-R1 retains much of the same microfluidic architecture of the Chip-S1® Stretchable Chip, including co-culture to model the tissue–tissue interface, independent perfusion of the apical and basal channels, and compatibility with Emulate’s instrumentation hardware. With a new polycarbonate tissue culture membrane, Chip-R1 is better suited for organ models that do not require mechanical stretch to mimic physiological functions like peristalsis, such as liver and kidney.

2.4. GC therapeutics

GC Therapeutics (MA, USA; www.gc-tx.com) has announced its US$75 million launch to scale and unlock the next generation of cell therapy [15]. The Company’s induced pluripotent stem cell (iPSC) programming platform, Transcription-Factor-ome (TFome™), integrates the latest advancements in synthetic biology, gene editing, cell engineering and machine learning to overcome the development and scaling complexities associated with cell therapy and improve patient access across a broad range of disease areas.

2.5. LumaCyte

LumaCyte,advanced cellular analysis and precision bioanalytics company, has launched its cell therapy application for predictive CAR T donor analytics [16]. Leveraging its novel Laser Force Cytology™ (LFC™) technology and Radiance® instrument, LumaCyte uncovered deep data insights into highly variable and complex patient and donor cellular starting material, enabling cell therapy developers to predict manufacturing success for specific donors or patients. To ensure that all interested partners can benefit from this powerful new application, LumaCyte has introduced a new donor qualification service where customers can ship donor or patient samples to LumaCyte for analysis and qualification. This service aims to revolutionize the cell therapy landscape by minimizing manufacturing risks due to variability in cellular starting material, enhancing production consistency, and increasing production yields.

2.6. Merck

Merck, (Germany; www.sigmaaldrich.com), a science and technology company, has achieved EXCiPACT cGMP certification for Pharmaceutical Auxiliary Materials (PAMs) at its major global Cell Culture Media (CCM) production sites [17]. EXCiPACT is a widely recognized standard for the manufacturing of non-sterile excipients. The company is the first in the industry to receive this certification.

EXCiPACT is a nonprofit organization that owns and manages the Certification Scheme available to pharmaceutical excipient manufacturers and distributors worldwide. Together with Merck, it developed the industry-first cGMP standard for Cell Culture Media. The new PAMs cGMP standard for CCM manufacturing was published in May 2023. Certified Merck sites are located in Darmstadt, Germany; Irvine, United Kingdom; Nantong, China; St. Louis, USA; and Lenexa, USA.

2.7. Syntax

Syntax Bio (IL, USA; www.syntax-bio.com), a preclinical-stage biotechnology company, has launched with raised US$15 million to advance its cell differentiation discovery platform [18]. The Syntax Cellgorithm platform mimics human developmental processes at the epigenetic level, using a modified CRISPR system to regulate endogenous genes in an automatic and temporally controlled manner.

3. Clinical trials

3.1. Pluripotent stem cells

3.1.1. BlueRock

BlueRock Therapeutics (MA, USA; www.bluerocktx.com), a clinical stage cell therapy company and wholly owned, independently operated subsidiary of Bayer (Germany; www.bayer.com), has announced positive 24-month data from exPDite, a Phase 1 clinical trial of bemdaneprocel, an investigational cell therapy for the treatment of Parkinson’s disease [19,20].

Bemdaneprocel (BRT-DA01) is an investigational cell therapy designed to replace the dopamine producing neurons that are lost in Parkinson’s disease. These dopaminergic neuron precursors are derived from pluripotent stem cells that are human embryonic stem cells. In a surgical procedure, these neuron precursors are implanted into the brain of a person with Parkinson’s disease. When transplanted, they have the potential to reform neural networks that have been severely affected by Parkinson’s and to restore motor and non-motor function to patients. In May 2024, bemdaneprocel received a Regenerative Medicine Advanced Therapy (RMAT) designation from the US FDA.

exPDite is a multi-center, multi-site, open-label, non-randomized, non-controlled phase 1 study. Twelve (12) subjects diagnosed with Parkinson’s disease received surgical transplantation of 1 of 2 different dose levels of bemdaneprocel to the post-commissural putamen bilaterally, and administration of a 1-year immunosuppression regimen. Cohort A (5 subjects) received a dose of 0.9 million cells per putamen. Cohort B (7 subjects) received 2.7 million cells per putamen. Safety and tolerability were assessed at 12 months as the primary endpoint, along with evidence of cell survival and motor effects. The feasibility of transplantation was also assessed. Assessments were repeated at 18 months with final assessments at 24 months.

The safety profile at 24 months is consistent with earlier findings, demonstrating that bemdaneprocel continues to be well tolerated by patients, with no adverse events reported related to bemdaneprocel. Transplanted cells continue to survive and engraft in the brain after discontinuing immunosuppression therapy at 12 months as outlined in the study’s protocol. In addition, secondary clinical endpoints related to motor symptoms continue to show positive trends from baseline through the duration of follow-up, with more encouraging trends in the high dose cohort than those in the low dose cohort. These were assessed by the MDS-Unified Parkinson’s Disease Rating Scale Part II and III (MDS-UPDRS Part II & III) and the Hauser PD Diary, tools used to assess Parkinson’s disease severity in motor symptoms. These consistent positive trends suggest that bemdaneprocel could potentially offer sustained benefit for movement impairments caused by the disease.

3.2. Immune cells

3.2.1. 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 opened enrollment for the Phase 1 clinical trial evaluating ADI-001 in autoimmune diseases [21].

ADI-001 is an investigational allogeneic gamma delta CAR T cell therapy targeting B-cells via an anti-CD20 CAR. ADI-001 was granted Fast Track Designation by the FDA for the potential treatment of relapsed/refractory class III or class IV lupus nephritis and relapsed or refractory B-cell NHL.

3.2.2. Estrella

Estrella Immunopharma(CA, USA; www.estrellabio.com), a clinical-stage biopharmaceutical company developing CD19 and CD22-targeted ARTEMIS® T-cell therapies to treat cancer and autoimmune diseases, has announced that the first patient enrolled in its STARLIGHT-1 Phase I/II clinical trial has achieved a complete response (CR) one month after receiving an infusion of EB103 CD19- Redirected ARTEMIS® T Cells [22,23].

The patient, diagnosed with follicular lymphoma grade 3A with high-risk 3B symptoms, was enrolled in the STARLIGHT-1 trial at UC Davis Comprehensive Cancer Center and received EB103 therapy after relapsing three times following prior treatments. Given the patient’s high tumor burden and multiple comorbidities, the patient was considered at high-risk, which might have increased the severity of side effects like cytokine release syndrome (CRS) and neurotoxicity with commercially available CAR-T treatments. However, no treatment-related serious adverse events (SAEs) were observed in this case.

The Phase I/II STARLIGHT-1 clinical trial is an open-label, dose escalation, multi-center, Phase I/II clinical trial to assess the safety of EB103 autologous T-cell therapy and to determine the Recommended Phase II Dose (RP2D) in adult subjects (≥18 years of age) who have relapsed/refractory (R/R) B-cell NHL. The study includes a dose escalation phase followed by an expansion phase.

3.2.3. Immusoft

Immusoft of CA, a wholly owned subsidiary of Immusoft Corporation (CA, USA; www.immusoft.com), a cell therapy company dedicated to improving the lives of patients with rare diseases, has announced positive results from the Phase 1 ISP-001 trial evaluating the therapy in a patient with mucopolysaccharidosis type I (MPS I) [24,25]. The first adult patient to receive ISP-001 in this study, with the Hurler-Scheie form of MPS I, experienced pharmacodynamic improvements, functional improvements, as well as reported improvements in quality of life, activities of daily living, and reductions in pain associated with MPS I. The administration of ISP-001 required no preconditioning regimen typically associated with other cell and gene therapeutics, and the infusion was well tolerated. There have been no adverse events reported as of 19 September 2024.

ISP-001 are autologous plasmablasts, a type of B cells, engineered to express the IDUA gene using the Sleeping Beauty transposon system.

3.2.4. J&J

Johnson & Johnson (NJ, USA; www.jnj.com) has announced long-term results from the Phase 3 CARTITUDE-4 study that show a single infusion of CARVYKTI® (ciltacabtagene autoleucel) significantly extended overall survival (OS) in patients with relapsed or lenalidomide-refractory multiple myeloma who have received at least one prior line of therapy, including a proteasome inhibitor (PI), reducing the risk of death by 45% versus standard therapies of pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide, and dexamethasone (DPd) [26,27]. With these data, CARVYKTI® is now the first and only cell therapy to improve OS versus standard therapies for patients with lenalidomide-refractory multiple myeloma as early as second line.

3.2.5. Ossium health

Ossium Health (CA, USA; https://ossiumhealth.com), a commercial-stage bioengineering company with the first-of-its-kind bone marrow bank for processing and deploying stem cell-based therapies, has announced positive preliminary outcomes for its first leukemia patient [7,28]. A 68-year-old female diagnosed with acute myeloid leukemia required an urgent bone marrow transplant following an unsuccessful four-month search for a matching donor. The patient received an infusion of 5.27 million CD34+ Ossium’s stem cells per kilogram of body weight from a donor that was a 4/8 hLA match to the patient. The doctors reported neutrophil engraftment by day 16 post-transplant and platelet engraftment by day 21. There have been no reported product-related adverse events to date.

Ossium sources bone marrow from the vertebral bodies of organ donors.

3.2.6. Poseida

Poseida Therapeutics (CA, USA; https://poseida.com/), a clinical-stage allogeneic cell therapy and genetic medicines company advancing differentiated non-viral treatments for patients with cancer and rare diseases, has announced that the US FDA granted Regenerative Medicine Advanced Therapy (RMAT) designation to p-BCMAALLO1, an investigational stem cell memory T cell (T)-based allogeneic CAR-T cell therapy in Phase 1/1b clinical development for the treatment of patients with relapsed/refractory multiple myeloma (RRMM) [29].

In a following press release the company announced new interim clinical data from its ongoing Phase 1 trial of p-BCMA-ALLO1 in patients with RRMM [30,31]. Total of 72 patients were enrolled in four arms. The data demonstrated that the overall response rate (ORR) across all four study arms was 54%; 11% of patients achieved a complete response (CR) or a stringent complete response (sCR), and 33% achieved a very good partial response or higher (VGPR+). Heavily pretreated 23 patients in Arm C (cyclophosphamide 750 mg/m²/day) demonstrated 91% ORR and compelling safety; 22% achieved a CR or an sCR, and 48% achieved VGPR+.

3.3. Gene therapy

3.3.1. Atamyo

Atamyo Therapeutics (France; https://atamyo.com), a clinical-stage biotechnology company focused on the development of new generation gene therapies targeting muscular dystrophies and cardiomyopathies, announced the enrollment of the last patient in the dose-escalation phase of its Phase 1b clinical trial of ATA-100, a gene therapy for patients with limb-girdle muscular dystrophy Type 2I/R9 (LGMD-2I/R9, protocol code ATA-001-FKRP) [32,33].

LGMD-2I/R9 is a rare genetic disease caused by mutations in the gene FKRP. It affects an estimated 5,000 people in the US and Europe. In the most common form, symptoms appear around late childhood or early adulthood. Patients suffer from progressive muscular weakness leading to loss of ambulation. They are also prone to respiratory impairment. There is currently no curative treatment for LGMD2I/R9. ATA-100, a single-administration gene therapy candidate for LGMD-2I/R9, delivers a normal copy of the gene for production of FKRP.

Atamyo also announced the filing of an Investigational New Drug (IND) application with the US FDA for a Phase 1b/2b clinical trial of its gene therapy, ATA-200, for patients with LGMD-2C/R5 [32,34]. LGMD-2C/R5 is a rare genetic disease caused by mutations in the gene that produces SGCG, a transmembrane protein that is involved in the connection between muscle fibers and their environment. It affects an estimated 2,000 people in Europe. In the classical form, symptoms appear in early childhood and patients suffer from progressive muscular weakness leading to loss of ambulation before adulthood. Cardiac involvement, typically presenting as dilated cardiomyopathy, is reported in approximately half of patients. There is no curative treatment. The management of LGMD-2C/R5 is solely supportive. ATA-200, the gene therapy for LGMD-2C/R5, delivers a normal copy of the gene for production of SGCG.

3.3.2. REGENEXBIO

REGENXBIO (MD, USA; www.regenxbio.com) announced positive results from the Phase I/II/III CAMPSIITE® trial of RGX-121 for the treatment of patients with Mucopolysaccharidosis Type II (MPS II), also known as Hunter syndrome. Hunter Syndrome, is a rare, X-linked recessive disease caused by a deficiency in the lysosomal enzyme I2S leading to an accumulation of glycosaminoglycans (GAGs), including heparan sulfate (HS), in tissues, which ultimately results in cell, tissue, and organ dysfunction, including in the central nervous system (CNS) [35–40].

RGX-121 is a potential one-time AAV therapeutic for the treatment of boys with MPS II. RGX-121 expressed protein is structurally identical to normal I2S. RGX-21 Delivery of the IDS gene within cells in the CNS could provide a permanent source of secreted I2S beyond the blood–brain barrier, allowing for long-term cross correction of cells throughout the CNS.

RGX-121 has received Orphan Drug Product, Rare Pediatric Disease, Fast Track, and Regenerative Medicine Advanced Therapy designations from the US FDA and advanced therapy medicinal products (ATMP) classification from the EMA.

CAMPSIITE is a Phase I/II/III multicenter, open-label trial for boys aged four months up to five years with neuronopathic MPS II. The primary endpoint of the trial is measurement of CSF GAGs. Accurate and sensitive measurements of CSF GAGs, such as HS D2S6, have the potential to be considered a surrogate endpoint that is reasonably likely to predict clinical benefit in MPS II disease under the accelerated approval pathway, as buildup of GAGs in the CSF of MPS II patients correlates with clinical manifestations including neurodevelopmental deficits.

The pivotal program is using commercial-scale cGMP material from REGENXBIO’s proprietary, high-yielding suspension-based manufacturing process, named NAVXpress™. In addition to measuring GAGs in the CSF, the trial will continue to collect neurodevelopmental data and caregiver-reported outcomes.

In new, long-term data from the Phase I/II/III CAMPSIITE® trial, patients receiving RGX-121 at the pivotal dose level demonstrated an 85% median reduction of cerebrospinal fluid (CSF) levels of heparan sulfate (HS) D2S6, a key biomarker of brain disease activity, approaching normal levels and sustained for up to two years.

3.3.3. Rocket

Rocket Pharmaceuticals (NJ, USA; https://rocketpharma.com), a fully integrated, late-stage biotechnology company advancing a sustainable pipeline of genetic therapies for rare disorders with high unmet need, has announced that all patients have been enrolled in the global, pivotal Phase 2 clinical trial evaluating RP-A501 to treat male patients with Danon disease [41,42].

Danon disease is caused by mutations in the LAMP2 gene. RP-A501 consists of a recombinant adeno-associated serotype 9 (AAV9) capsid containing a full-length, wild-type version of the human LAMP2B transgene (AAV9.LAMP2B) which, when inserted into heart cells harboring mutations in the endogenous LAMP2 gene, has potential to fully restore cardiac function at its root. RP-A501 represents a single-dose treatment and is administered as an intravenous infusion. In preclinical and clinical studies, AAV9.LAMP2B has been shown to target cardiomyocytes and deliver the functional LAMP2B gene to heart tissue, which ultimately leads to improved cardiac structure and function in patients.

In 2023, the US FDA granted regenerative medicine advanced therapy designation, and the European Medical Agency granted PRIority MEdicines (PRIME) eligibility to RP-A501.

4. Regulations, approvals, acquisitions …

4.1. Green light

4.1.1. BlueRock

BlueRock Therapeutics (MA, USA; www.bluerocktx.com), a clinical stage cell therapy company and wholly owned, independently operated subsidiary of Bayer (Germany; www.bayer.com), has announced the clearance of its Investigational New Drug (IND) application by the US FDA for OpCT-001, an investigational induced pluripotent stem cell (iPSC)-derived cell therapy for the treatment of primary photoreceptor diseases [43].

OpCT-001 is the first investigational iPSC-derived cell therapy to be clinically evaluated for the treatment of primary photoreceptor diseases. Initiation activities to support a Phase 1/2a study are underway. The Phase 1/2a study is designed as a first-in-human study to evaluate the safety and tolerability of subretinal administration of OpCT-001 in people with primary photoreceptor diseases as well as evaluate the effect of OpCT-001 on retinal structure, visual function, and functional vision. The study will assess several dose levels of OpCT-001 and is expected to enroll participants in sites across the U.S.

OpCT-001 was exclusively licensed from FUJIFILM Cellular Dynamics (WI, USA; www.fujifilmcdi.com) and Opsis Therapeutics (WI, USA; https://opsistx.com) in January 2024 as part of the strategic R&D and clinical manufacturing collaboration between BlueRock Therapeutics, FUJIFILM Cellular Dynamics, and Opsis Therapeutics forged in 2021. As part of the collaboration, FUJIFILM Cellular Dynamics supported BlueRock Therapeutics via research, development, and the execution of critical IND-enabling activities including the clinical manufacturing of OpCT-001

4.1.2. Kiromic

Kiromic BioPharma (TX, USA; https://kiromic.com/) has announced that the De-ltacel-01 Safety Monitoring Committee (SMC) has unanimously voted in favor of proceeding with the expansion phase of the Deltacel-01 clinical trial [44,45]. This trial is evaluating Deltacel™ (KB-GDT-01), the Company’s allogeneic, off-the-shelf, Gamma Delta T-cell (GDT) therapy, in patients with stage 4 metastatic non-small cell lung cancer (NSCLC) who have failed to respond to standard therapies.

This recommendation by the SMC follows a favorable review of safety data from the first two cohorts, including recent results from the 40-day follow-up visit of the sixth patient in Deltacel-01, which demonstrated a positive safety and tolerability profile with no dose-limiting toxicities (DLTs) observed. As part of the expansion phase of Deltacel-01, Kiromic will enroll approximately nine patients.

4.1.3. 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 Regenerative Medicine Advanced Therapy (RMAT) designation to OBX-115 for the treatment of patients with unresectable or metastatic melanoma that is resistant to immune checkpoint inhibitor (ICI) therapy [46,47]. OBX-115 is a novel engineered tumor-derived autologous T cell immunotherapy (tumor-infiltrating lymphocyte [TIL] cell therapy) armored with membrane-bound IL15 (mbIL15) that is pharmacologically regulated using FDA-approved small-molecule drug acetazolamide. This second FDA designation follows a July 2024 announcement of Fast Track designation for OBX-115. Obsidian is investigating OBX-115 in a multicenter trial in patients with advanced melanoma or relapsed/refractory NSCLC (NCT06060613).

4.1.4. Synthekine

Synthekine (CA, USA; www.synthekine.com), an engineered cytokine therapeutics company, has announced that the US FDA has granted Fast Track designation to SYNCAR-001 + STK-009, its CD19 CAR-T and orthogonal IL-2 investigational therapy, for the treatment of patients with severe, refractory systemic lupus erythematosus (SLE), without the use of lymphodepletion [48]. SYNCAR-001 + STK-009 is a cytokine-inducible cell therapy regimen built on Synthekine’s proprietary orthoIL- 2 technology. It is a two-component therapy consisting of SYNCAR-001, an autologous CD19-targeting chimeric antigen receptor T cell (CAR-T) which expresses an engineered IL-2 receptor allowing it to selectively receive a signal from STK-009, an engineered IL-2 cytokine. SYNCAR-001 + STK-009 has been administered to patients with CD19+ hematologic malignancies in an ongoing Phase 1 study [49]. The FDA recently cleared an IND application for a Phase 1 study [50] of SYNCAR-001 + STK-009 in nonrenal SLE and lupus nephritis (LN).

5. Capital market & finances

5.1. 2seventy bio and BMS

2seventy bio (MA, USA; www.2seventybio.com) has announced that the Company, in partnership with study sponsor Bristol Myers Squibb (NY, USA; www.bms.com), will discontinue enrollment in its ongoing Phase 3 KarMMa-9 study evaluating Abecma® (idecabtagene vicleucel; ide-cel) with lenalidomide maintenance versus lenalidomide maintenance alone in patients with newly diagnosed multiple myeloma who have suboptimal response to autologous stem cell transplant [51,52]. This decision will conserve over US$80 million in near-term expenditures and accelerate the Company’s path to breakeven in 2025.

5.2. AcuraStem

AcuraStem (CA, USA; https://acurastem.com), a patient-based biotechnology company advancing treatments for amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other neurodegenerative diseases announced today that it has successfully secured US$4 million in grant funding from the California Institute for Regenerative Medicine (CIRM; CA, USA; www.cirm.ca.gov) [53].

This latest funding will specifically support AcuraStem’s continued efforts to advance its targeted therapeutic program for the UNC13A gene, using its iNeuroRx® technology platform. iNeuroRx® has been instrumental in the company’s development of targeted therapeutics focused on the UNC13A gene, which plays a crucial role in the pathophysiology of ALS and FTD.

5.3. Atara biotherapeutics

Atara Biotherapeutics (PA, USA; www.atarabio.com), a T-cell immunotherapy company, leveraging its novel allogeneic Epstein–Barr virus (EBV) T-cell platform to develop transformative therapies for patients with cancer and autoimmune diseases, has entered into definitive agreements for the issuance and sale of 758,900 shares of its common stock at a purchase price of US$8.25 per share and the issuance and sale of pre-funded warrants to purchase up to 3,604,780 shares of its common stock at a purchase price of US$8.2499 per share in a registered direct offering, representing a premium of 15% to Atara’s 7-day volume-weighted average price [54]. The pre-funded warrants will have an exercise price of US$0.0001 per share and will be immediately exercisable upon issuance.

The gross proceeds to Atara from the offering are expected to be US$36 million, before deducting estimated offering expenses payable by Atara. Atara currently intends to use the net proceeds from the offering for working capital and general corporate purposes.

5.4. Arsenal Bio

Arsenal Biosciences (CA, USA; https://arsenalbio.com), a clinical stage programmable cell therapy company focused on engineering advanced CAR T-cell therapies for solid tumors, has closed an oversubscribed US$325 million Series C financing round [55]. Proceeds from the financing will be used to advance ArsenalBio’s lead programs through development as the company continues to build its pipeline of therapeutic candidates for solid tumor cancers based on its proprietary T cell engineering technology, including logic gating. The funds will also drive further innovation in developing tools and processes for identifying new candidate cell therapies, helping ArsenalBio remain at the forefront of the rapidly evolving field of cell therapy and bringing it closer to its goal of addressing unmet needs across the oncology category.

5.5. Bluebird bio

Following a comprehensive review of its operations, bluebird bio (MA, USA; www.bluebirdbio.com) has announced that the Company is implementing a restructuring intended to optimize the Company’s cost structure and enable quarterly cash flow break-even in the second half of 2025 [56]. The restructuring is expected to result in a 20% reduction in cash operating expenses when fully realized in Q3 2025, compared to the prior reporting period. The initiative includes a reduction in the Company’s workforce of approximately 25%. The Company’s cash flow break-even target assumes scaling to approximately 40 drug product deliveries per quarter, realizing the 20% reduction in cash operating expenses, and obtaining additional cash resources to extend the Company’s cash runway.

5.6. Cartherics

Cartherics (VIC, Australia; https://cartherics.com), a biotechnology company developing immune cell therapies for the treatment of cancer and other diseases, has successfully raised well over its target AU$15 M in an oversubscribed financing round [57]. This funding will support the initiation of the clinical trial for CTH-401, the Company’s lead cell therapy product, aimed at treating ovarian cancer, as well as broadening its pipeline to include other disease indications.

CTH-401 is the only natural killer (NK) cell product currently under development that incorporates a chimeric antigen receptor (CAR) that targets the adenocarcinoma-specific antigen, TAG-72. TAG-72 is a well-validated tumor marker that is widely expressed in a range of solid tumors, including ovarian, gastric, colorectal, prostate, and pancreatic cancers. Cartherics has demonstrated that CTH-401 is very effective in killing ovarian cancer cells in both tissue culture and animal models, with the initiation of the first clinical trial planned for next year.

5.7. Sonoma

Sonoma Biotherapeutics (CA, USA; https://sonomabio.com), a clinical-stage biotechnology company developing engineered regulatory T cell (Treg) therapies for autoimmune and inflammatory diseases, has received a US$45 million milestone payment from Regeneron Pharmaceuticals (NY, USA; www.regeneron.com), under the terms of its active collaboration to discover, develop, and commercialize engineered Treg therapies for autoimmune diseases [58].

Under the terms of the agreement, Sonoma Bio received US$75 million in upfront payments, which included a US$30 million equity investment in Sonoma Bio by Regeneron. Sonoma Bio was also eligible to receive an additional US$45 million development milestone payment, which has now been achieved. The parties are equally co-funding research and development for all potential products and will share equally any future commercial expenses and profits. Regeneron will have the option to lead late-stage development and commercialization on all products globally, with Sonoma retaining rights to co-promote all such products in the United States.

Sonoma Bio continues to retain full ownership of its lead Treg cell therapy candidate, SBT-77-7101, and other programs in development. The company has two ongoing Phase 1 trials of SBT-77-7101 in rheumatoid arthritis and hidradenitis suppurativa.

Funding Statement

This paper was not funded.

Disclosure statement

Dusko Ilic is a member of the Regenerative Medicine Editorial Board. They were not involved in any editorial decisions related to the publication of this article. 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.

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