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

Business Development

Collaboration agreement: Landmark Bio & InnDura

Landmark Bio (MA, USA; www.landmarkbio.com), a statutory public benefit limited liability company, and InnDura Therapeutics (MA, USA; https://labcentral.org/resident-companies/inndura-therapeutics/), a newly formed company advancing natural killer (NK) cell research, have announced a new collaboration to develop and execute product development, regulatory and chemistry, manufacturing and control strategies to progress InnDura's lead program to the clinic [1]. InnDura is using EVE16, a non-chimeric antigen receptor (non-CAR) engineering approach that provides enhanced cancer cell killing with greatly reduced cellular exhaustion and fratricide. The EVE16 technology can also be applied to T cells and other forms of cell therapy.

Collaboration & license agreement: Quell & Astra Zeneca

Quell Therapeutics (UK; https://quell-tx.com), a company developing engineered T-regulatory (Treg) cell therapies for serious medical conditions driven by the immune system, has entered into a collaboration, exclusive option and license agreement with AstraZeneca (UK; www.astrazeneca.com) to develop, manufacture and commercialize autologous, engineered Treg cell therapies for two autoimmune disease indications [2]. Under the terms of the agreement, Quell's proprietary toolbox of Treg cell engineering modules, including its Foxp3 Phenotype Lock, will be leveraged to develop autologous multi-modular Treg cell therapy candidates for Type 1 diabetes (T1D) and inflammatory bowel disease (IBD). AstraZeneca will have the option to further develop and commercialize successful candidates, with Quell responsible for the process development and manufacturing of clinical candidates through to the end of the first-in-human clinical study.

Quell will receive US$85 million upfront from AstraZeneca, which comprises a predominant cash payment and an equity investment. Quell is also eligible to receive over $2 billion for further development and commercialization milestones, if successful, plus tiered royalties. In addition, Quell retains an option, which can be exercised either after approval of an Investigational New Drug (IND) application or at the end of the phase I/II clinical study, to co-develop Treg cell therapies from the T1D program with AstraZeneca in the USA in exchange for additional milestone payments and increased royalties on US net sales.

Quell retains full ownership of its lead Treg cell therapy candidate QEL-001, which is designed to prevent organ rejection and eliminate the need for lifelong immunosuppression in liver transplant patients and is expected to enter first-in-human trials during 2023, as well as its preclinical program in neuroinflammation.

Partnership agreement: Pluristyx/panCella & CIRM

Pluristyx and panCELLa (WA, USA; www.pluristyx.com), a merged biotechnology company, were accepted as an Industry Resource Partner with the California Institute for Regenerative Medicine (CIRM; CA, USA; www.cirm.ca.gov) [3]. This partnership provides CIRM awardees with improved access to Pluristyx/panCELLa's highly-characterized and genetically-modified induced pluripotent stem cells (iPSCs) containing industry-leading FailSafe™ and iACT Stealth Cell ™ technologies.

Approved iPSC lines are available under Pluristyx/panCELLa's unique ‘try-before-you-buy’ research evaluation model, allowing CIRM awardees to assess the suitability of multiple lines in parallel to select an appropriate line prior to licensing. All Pluristyx/panCELLa iPSCs are derived from fully-consented and regulatory appropriate donors procured under Good Tissue Practices (GTP) to provide streamlined access to a clinical-grade version for human trials. All iPSCs can be made available in Pluristyx/panCELLa's proprietary Ready-to-Differentiate^® format to allow for rapid evaluation and downstream manufacturing by eliminating the need for additional expansion out of thaw. Pluristyx/panCELLa can further assist CIRM grantees with customized cell line and process development services as needed to speed the transition of their revolutionary therapies into the clinic.

Strategic manufacturing collaboration: Vertex & Lonza

Vertex Pharmaceuticals (MA, USA; www.vrtx.com) and Lonza (Switzerland; www.lonza.com) have announced a strategic collaboration to support the manufacture of Vertex's portfolio of investigational human embryonic stem cell (hESC)-derived, fully differentiated insulin-producing islet cell therapies for people with T1D, currently focusing on the VX-880 and VX-264 programs that are currently in clinical trials [4]. VX-800 and VX-264 utilizes the same fully differentiated insulin-producing islet cells, encapsulated in different devices.

Under the terms of the collaboration, Vertex and Lonza will partner in the process development and scale-up for the manufacturing of the product portfolio and co-invest to build a dedicated new facility in Portsmouth, NH, USA. Operated by Lonza, the facility will span more than 12,000 m² and is anticipated to create up to 300 new jobs at peak capacity. Construction is scheduled to begin later this year.

Achievements, launches…

Cambrian Bio

Cambrian Bio (NY, USA; www.cambrianbio.com), a clinical-stage biotechnology company focused on treating and preventing chronic diseases of aging, has announced the launch of its new pipeline company, Telos Biotech [5]. The organization will develop Telovance™, a novel recombinant protein delivered intracellularly during the ex vivo manufacturing of CAR-T cells.

Rapid telomere shortening naturally occurs during the ex vivo cell expansion portion of cell therapies, a medical procedure in which an organ, cells, or tissue are taken from a living body for a treatment or procedure, and then returned to the living body. During this process, critically shortened telomeres have emerged as a key barrier to successful CAR-T cell immunotherapy. Ultimately, the cells are unable to fully eliminate malignancy and provide durable and persistent protection against recurrent disease. By safely lengthening telomeres during the ex-vivo manufacturing process, Telos can rewind the cellular biological clock and unlock the potential of cell immunotherapy. With these findings, Telos has engineered Telovance™, a recombinant protein that can be easily incorporated into the cell therapy manufacturing process. Telos has a patent portfolio directed to this technology.

Curi Bio

Curi Bio, a developer of human stem cell-based platforms for drug discovery (WA, USA; www.curibio.com), has launched their MantaReady™ iPSC-Derived Skeletal Muscle Myoblasts specifically optimized for creating human 3D engineered muscle tissues for preclinical therapeutic discovery, high-throughput screening and disease modelling [6].

The myoblast lines were developed in response to the growing demand for high quality iPSC-derived cells required for 3D skeletal muscle engineering. Large cell expansions are necessary to provide sufficient cell numbers to fabricate 3D organoids. The traditional process of expanding cells for 3D tissues is not only time consuming, but also leads to decreased cell purity and viability with multiple passages, resulting in suboptimal muscle tissue function. MantaReady cells are quality controlled to ensure optimal performance and cryopreserved in high density to enable direct cell thaw tissue casting. This time saving and variability-reducing approach eliminates the need to expand myoblasts for tissue engineering and downstream assays.

MantaReady iPSC-Derived Skeletal Muscle Myoblasts are currently provided in two formats: a wildtype line produced using iPSCs from a healthy donor and a Duchenne muscular dystrophy disease line harboring an exon 45 deletion and a 17bp deletion in exon 54 to ensure a true dystrophin null.

Nanotein

Nanotein Technologies (CA, USA; https://nanoteintech.com), a manufacturer of innovative cell therapy reagents, has launched their latest addition to the NanoSpark™ product line: NanoSpark™ GROW-NK Soluble Activator [7]. This reagent enables for the feeder cell free activation and expansion of human NK cells, ex vivo, to advance cancer immunotherapy development and manufacturing.

Researchers can use this revolutionary and soluble, protein-based activator to easily expand for a large-volume of high-quality NK cells without needing magnetic components. The nanoscale format of the activator's proprietary protein complex also allows scientists to use sterile filtration, a desirable novelty in NK immunotherapy.

Organa Bio

OrganaBio (FL, USA; www.organabio.com) has launched NeoPAC™ placenta and umbilical cord tissues, its latest suite of products designed to accelerate the progress of regenerative medicine and cell therapy [8]. By offering both Research Use Only and clinical (cGMP) grade tissues, OrganaBio empowers researchers to tap into the potential of birth tissues, enabling the development of innovative therapies to address a wide range of medical conditions.

Parse

Parse Biosciences (WA, USA; www.parsebiosciences.com), a provider of accessible and scalable single cell sequencing solutions, has launched CRISPR Detect, which enables single-cell pooled CRISPR screens at unprecedented scale [9]. Bulk pooled CRISPR screening has been a valuable tool to understand gene function on a genome scale. Adding single cell resolution to pooled CRISPR screens pairs individual gene perturbations with rich whole transcriptome expression phenotypes. This approach has expanded the capabilities of pooled CRISPR screening to understand cell types of perturbed cells and quantify changes in gene expression, regulatory networks, signaling pathways and other complex signatures. However, the applications and scale of these studies have been limited by the throughput and cost of droplet-based single cell RNAseq technology.

CRISPR Detect brings the scale of existing Parse Evercode technology to single cell CRISPR screening by enabling users to pair perturbations and transcriptional profiles in up to 1 million cells in a single experiment. This scale will expand the applications of single cell CRISPR screening particularly in drug discovery where cost has limited their use to targeted validation studies.

StemBioSys

StemBioSys (TX, USA; www.stembiosys.com) has launched CELLvo™ Atrial Cardiomyocyte, a technological leap forward in cardiotoxicity screening [10]. CELLvo™ Atrial Cardiomyocyte are non-genetically modified human chamber specific iPSC-derived heart cells.

Clinical trials

Mesenchymal stromal/stem cells (MSC)

Athersys

Athersys (OH, USA; www.athersys.com), a regenerative medicine company developing MultiStem^® (invimestrocel) cell therapy for critical care indications, has started patient enrolment of 140 patients in the third and final cohort in MATRICS-1, the phase II clinical study evaluating MultiStem in patients following resuscitation from hemorrhagic trauma [11,12].

Patients in the third cohort will be dosed with MultiStem cells produced under Athersys' novel 3D bioreactor-based manufacturing process that was first utilized to produce product for patients in cohort two of MATRICS-1. MultiStem is believed to deliver benefit for treating complications due to trauma through mechanisms including reducing inflammatory damage, protecting at-risk tissue at the site of injury and upregulating reparative aspects of the local and systemic immune system in a timelier way.

Immune cells

Bristol Myers Squibb

Bristol Myers Squibb (NJ, USA; www.bmb.com) has the first disclosure of primary analysis results from two pivotal studies evaluating Breyanzi (lisocabtagene maraleucel; liso-cel), TRANSCEND FL, an open-label, global, multicenter, phase II, single-arm study in patients with relapsed or refractory follicular lymphoma (FL) and the relapsed or refractory mantle cell lymphoma (MCL) cohort of TRANSCEND NHL 001, an open-label, multicenter, phase I, single-arm, seamless-design study [13–15].

Among 101 patients treated in TRANSCEND FL study, the overall response rate (ORR) was 97%, with 94% of patients achieving a complete response (CR). Median follow-up is 16.6 months.

In the MCL cohort of TRANSCEND NHL 001, with a median on-study follow-up of 16.1 months, the ORR in patients evaluated for efficacy in the primary analysis set (n = 74) was 86.5%, with 74.3% of patients achieving a CR.

Carisma

Carisma Therapeutics (PA, USA; https://carismatx.com), a clinical stage biopharmaceutical company focused on discovering and developing innovative immunotherapies, has announced that the first patient has been dosed in its phase I clinical trial that will test the safety and tolerability of the Company's lead product candidate, CT-0508, a HER2-targeted chimeric antigen receptor macrophage (CAR-M) in combination with Merck's anti-PD1 therapy KEYTRUDA^® (pembrolizumab) for the treatment of HER2 overexpressing cancers [16,17]. This first patient's cells were manufactured at the Novartis Cell Therapy Site in Morris Plains, New Jersey, following the successful completion of the tech transfer of CT-0508 to Novartis earlier this year. This is Carisma's first clinical product to be manufactured and administered from this collaboration.

Curocell

Curocell (South Korea; https://curocellbtx.com/en/), a clinical-stage CAR-T cell therapy company, has announced updated phase II interim results for anbalcabtagene-autoleucel (anbal-cel) [18]. The anbal-cel is the next-generation OVIS technology applied to anti-CD19 CAR-T using the 4-1BB domain as a co-stimulation domain and a dual knockdown system for two immune checkpoint receptors, PD-1 and TIGIT, in CAR-T cells. The phase II study of anbal-cel was conducted to evaluate the efficacy and safety in patients with relapsed/refractory large B-cell lymphoma (r/r LBCL). Patients with relapsed or refractory LBCL were enrolled in six Korean investigator sites to receive anbal-cel at a dose of 2 × 10 CAR-T cells/kg. 41 patients with r/r LBCL were infused with anbal-cel. All patients received two or more prior lines of therapy and 10% (4 of 41) received ≥4 prior lines of treatment before the study. Overall response rate of 84% (32/38), and complete response in 71% (27/38) were reached. Complete response at 3 months was 61% (19/31) and at 6 months was 60% (12/20) where median follow-up as 6.3 months.

Grace Bio

Gracell Biotechnologies (China; www.gracellbio.com), a global clinical-stage biopharmaceutical company dedicated to developing innovative and highly efficacious cell therapies for the treatment of cancer and autoimmune disease, has presented longer-term follow-up data from a first-in-human study evaluating GC012F, a CD19 and B-cell maturation antigen (BCMA) dual-targeted autologous CAR-T therapeutic candidate, in patients with relapsed/refractory B-cell non-Hodgkin's Lymphoma (r/r B-NHL) [19,20]. While CD19-directed CAR-T cell therapy has been demonstrated to be a valuable treatment option for r/r B-NHL, other studies have identified that 39% to 97% of clinical B-NHL samples express BCMA as well.1,2,3 To further improve safety and efficacy of NHL treatment, Gracell is exploring the clinical potential of GC012F, a CD19 and BCMA dual-targeting CAR-T cell therapy, for treatment of r/r B-NHL. GC012F is manufactured through a novel next-day FasTCAR process and demonstrated a younger phenotype of CAR-T cells and highly effective tumor killing activity in preclinical animal models.

In the single-arm, open-label, investigator-initiated trial (IIT), nine r/r B-NHL patients were enrolled and treated with GC012F and completed at least 3 months of follow-up. Doses range between 3.7 × 104 to 3 × 105 CAR-T cells/kg. All nine patients are classified as relapsed/refractory DLBCL. All patients' lymphoma samples expressed CD19, and samples from seven out of eight tested patients expressed BCMA. With a median follow-up of 293 days (range: 131–546 days), patients treated with GC012F achieved a high response rate and outstanding durability of response: 100% (9/9) overall response rate (ORR) at 3 months, 77.8% (7/9) complete response (CR) rate at 3 months, and 66.7% (6/9) CR rate at 6 months.

IASO & Innovent

IASO Biotechnology (China; www.iasobio.com), a clinical-stage biopharmaceutical company engaged in discovering, developing and manufacturing innovative cell therapies and antibody products and Innovent Biologics (China; www.innoventbio.com), have jointly announced the updated data from phase Ib/II study of equecabtagene autoleucel (IASO Bio R&D code: CT103A, Innovent R&D code: IBI326), an anti-BCMA CAR T-cell therapy for the treatment of relapsed and/or refractory multiple myeloma (r/r MM) [21,22]. CT103A (equecabtagene autoleucel) is a CAR-T therapy featuring fully human BCMA-targeting single-chain fragment variable (scFv) antibody. The updated data showed long term follow-up efficacy and safety of the phase 1b/2 study (FUMANBA-1) conducted in 14 centers in China. This study enrolled r/r MM patients who received ≥3 lines of prior therapies containing at least a proteasome inhibitor and an immunomodulatory agent and were refractory to their last line of treatment.

Among the 101 evaluable patients, the ORR was 96.0% (97/101), with 91.1% (92/101) of those patients achieving very good partial response (VGPR) or deeper response, and the stringent complete response/ complete response (sCR/CR) rate was 74.3% (75/101). The median time-to-response (mTTR) was 16 days (range: 11–179). The median duration of response (DOR) and median progression free survival (PFS) have not been reached. The 12-month PFS rate was 78.8%.

In 89 patients without prior CAR-T therapy, ORR was 98.9% (88/89), including 78.7% (70/89) of patients reaching CR/sCR. Of the 63 patients with ≥12 months follow-up (including patients that withdrew early), ORR was 98.4% (62/93) and 87.3% (55/63) reached sCR/CR. Of the 12 patients with prior CAR-T therapy, 75% (9/12) achieved response, and five patients achieved sCR (including four patients that sustained sCR for over 18 months post-infusion).

Kite

Kite Pharma (CA, USA; www.kitepharma.com), a Gilead Company (CA, USA; www.gilead.com), has published detailed results from the overall survival analysis of the landmark phase III ZUMA-7 study of Yescarta^® (axicabtagene ciloleucel [axi-cel]) CAR T-cell therapy compared with historical standard of care (SOC) as initial treatment in the curative setting for patients with relapsed or refractory large B-cell lymphoma (r/r LBCL) [23–25]. Yescarta is the first treatment in nearly 30 years to demonstrate a significant improvement in survival in this patient population. With a median follow-up of 4 years (47.2 months), a one-time treatment with Yescarta demonstrated significantly longer overall survival compared with SOC with a 27.4% reduction in the risk of death, which corresponds to a 38% relative improvement in overall survival, for patients with r/r LBCL within 12 months completion of first-line therapy.

Legend Bio

Legend Biotech Corporation (NJ, USA; https://legendbiotech.com) and Janssen Pharmaceutical Companies (Belgium; www.janssen.com) of Johnson & Johnson (NJ, USA; www.jnj.com) have published the results from the phase III CARTITUDE-4, the first randomized study investigating the efficacy of a cell therapy versus standard of care as early as after first relapse in lenalidomide-r/r MM [26–29]. A total of 419 patients underwent randomization (208 to receive cilta-cel and 211 to receive standard care). The results show that, at a median follow-up of 16 months, cilta-cel reduced the risk of disease progression or death by 74% compared with standard of care regimens in adult patients with multiple myeloma who have received one to three prior lines of therapy and are refractory to lenalidomide. Progression-free survival at 12 months was 75.9% in the cilta-cel group and 48.6% in the standard-care group.

A final analysis of data from the phase Ib/II CARTITUDE-1 study showed sustained deep and durable responses in heavily pretreated patients with relapsed or refractory multiple myeloma treated with cilta-cel [30]. At a median follow-up of 33.4 months (range, 1.5–45.2), the median progression-free survival was 34.9 months, with an estimated 47.5% of patients progression-free and alive at 36 months.

CARVYKTI^® (ciltacabtagene autoleucel; www.carvykti.com) is a B-cell maturation antigen (BCMA)-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory multiple myeloma, after four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

Precigen

 Precigen (MD, USA; https://precigen.com), a biopharmaceutical company specializing in the development of innovative gene and cell therapies to improve the lives of patients, has presented positive data from the phase I study that demonstrate a favorable safety profile for PRGN-3005 UltraCAR-T [31,32]. PRGN-3005 UltraCAR-T is an autologous CAR-T cell therapy manufactured using non-viral gene delivery and is under investigation for the treatment of patients with advanced, recurrent platinum resistant ovarian, fallopian tube or primary peritoneal cancer. PRGN-3005 utilizes Precigen's transformative UltraCAR-T therapeutic platform, which eliminates ex vivo expansion and reduces manufacturing time to allow for rapid next day administration of UltraCAR-T cells following non-viral gene transfer. PRGN-3005 UltraCAR-T is a multigenic CAR-T cell investigational therapy utilizing Precigen's advanced non-viral gene delivery system to co-express a chimeric antigen receptor, membrane-bound IL-15 (mbIL15), and a kill switch for better precision and control.

The study population includes patients with advanced stage (III/IV) recurrent ovarian, fallopian tube, and primary peritoneal cancer who are platinum resistant and have progressed after receiving standard-of-care therapies or are not eligible to receive available therapies with known clinical benefit. Among 27 patients treated so far, the best responder achieved stable disease for more than 18 months after failing 9 prior lines of treatment; results achieved with two doses of UltraCAR-T cells in the low millions.

Pluripotent stem cells

BlueRock

Bayer AG (Germany; www.bayer.com) and BlueRock Therapeutics (MA. USA; www.bluerocktx.com), a clinical stage cell therapy company and wholly owned independently operated subsidiary of Bayer AG, have announced positive top-line results from a phase I clinical trial of investigational drug, bemdaneprocel (BRT-DA01), a potential first-in-class cell therapy for Parkinson's disease [33,34]. Bemdaneprocel (BRT-DA01), an investigational therapy comprised of dopamine producing neurons derived from pluripotent stem cells, is surgically implanted into the brain of a person with Parkinson's disease. When transplanted, these cells have the potential to reform neural networks that have been destroyed by Parkinson's disease in the hope of restoring motor and non-motor function to patients. The trial showed that bemdaneprocel was well-tolerated in all 12 patients in the study to date, with no major safety events. In addition, an assessment of the study's secondary end points demonstrated feasibility of transplantation and evidence of cell survival and engraftment in the brain through 1 year. Based on these results, planning is underway for a phase II study that is expected to begin enrolling patients in first half of 2024.

Vertex

Vertex Pharmaceuticals (MA, USA; www.vrtx.com) presented data on all patients dosed in Parts A and B of its phase I/II clinical trial of VX-880, an investigational stem cell-derived, fully differentiated islet cell therapy, in people with T1D with impaired hypoglycemic awareness and severe hypoglycemic events (SHEs) [35,36]. All six patients treated with VX-880 had undetectable fasting C-peptide (marker of endogenous insulin secretion) at baseline, a history of recurrent SHEs in the year prior to treatment and required an average of 34.0 units of insulin per day. Following treatment, all six patients demonstrated endogenous insulin secretion, improved glycemic control as measured by HbA1c, improved time-in-range on continuous glucose monitoring, and reduction or elimination of exogenous insulin use. Patients with greater than 90 days of follow-up had elimination of SHEs in the evaluation period.

Hematopoietic stem cells

Vertex

Vertex Pharmaceuticals (MA, USA; www.vrtx.com) and CRISPR Therapeutics (Switzerland; https://crisprtx.com) have announced that both pivotal trials for exagamglogene autotemcel (exa-cel) in patients with transfusion-dependent beta thalassemia (TDT) or severe sickle cell disease (SCD) met primary and key secondary end points at pre-specified interim analyses [37,38]. These analyses evaluated the efficacy and safety of exa-cel in patients with TDT or SCD in the ongoing phase III trials as well as in the long-term follow-up trial CLIMB-131. The data shared are from 83 patients (48 with TDT and 35 with SCD) dosed with exa-cel with follow-up up to 43.7 months. All patients treated with exa-cel demonstrated clinical benefit, and these data continue to demonstrate the potentially transformative profile of exa-cel.

Exa-cel is an investigational, autologous, ex vivo CRISPR/Cas9 gene-edited cell therapy that is being evaluated for patients with SCD or TDT, in which a patient's own hematopoietic stem cells are edited to produce 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. The elevation of HbF by exa-cel has the potential to reduce or eliminate painful and debilitating VOCs for patients with SCD and alleviate transfusion requirements for patients with TDT.

Other

Amplifica

Following the publication of their research into a naturally occurring process for hair growth that may lead to the treatment of hair loss, Amplifica Holdings Group (CA, USA; https://amplificabio.com), a privately held, clinical-stage biopharmaceutical company announced the initiation of the first-in-human multicenter study of its lead candidate AMP-303 [29–41]. The primary objective of this initial study is to evaluate the safety and tolerability of AMP-303 along with an assessment on hair count in subjects with androgenetic alopecia. Osteopontin, the compound highlighted in the publication is referenced as AMP-203 at Amplifica.

Regulations, approvals, acquisitions…

Mergers & acquisitions

Eli Lilly & Sigilon

Eli Lilly and Company (IN, USA; www.lilly.com) and Sigilon Therapeutics (MA, USA; https://sigilon.com) have announced a definitive agreement for Lilly to acquire Sigilon, a biopharmaceutical company that seeks to develop functional cures for patients with a broad range of acute and chronic diseases [42]. Since 2018, Lilly and Sigilon have worked together to develop encapsulated cell therapies, including SIG-002, for the treatment of Type 1 diabetes.

Under the terms of the definitive agreement, Lilly will commence a tender offer to acquire all outstanding shares of Sigilon for a purchase price of US$14.92 per share in cash (an aggregate of approximately US$34.6 million) payable at closing, plus one non-tradeable contingent value right per share that entitles the holder to receive up to an additional US$111.64 per share in cash, for a total potential consideration of up to US$126.56 per share in cash without interest, an aggregate of up to approximately US$309.6 million excluding shares held by Lilly.

RoslinCT & Lykan

RoslinCT (UK; www.roslinct.com) and Lykan Bioscience, two leading Contract Development and Manufacturing Organizations (CDMOs) in the Cell and Gene Therapy industry, have announced their integration, creating a unified business that will operate under the RoslinCT brand [43]. The state-of-the-art manufacturing facilities located in Edinburgh, Scotland, and Boston, USA, will remain operational under the RoslinCT brand, with plans for further capacity expansion on both sides of the Atlantic, to meet the global growing demand for Advanced Cell and Gene Therapy manufacturing services.

Green light

Bristol Myers Squibb

Bristol Myers Squibb (BMS; NJ, USA; www.bmb.com) has announced that the US FDA has approved commercial production at the company's newest cell therapy manufacturing facility in Devens, MA, USA [44]. The Devens site is a critical component of BMS’ expanding global cell therapy manufacturing footprint for long-term supply of the company's cell therapy portfolio. Manufacturing autologous cell therapies is both operationally and technically complex because they are uniquely created using an individual patient's own T cells as the starting material. Each batch of engineered T cells is manufactured individually and infused back to the original cancer patient. It is important to develop reliable quality supply with rapid turnaround time. The expansion of the company's global manufacturing footprint is critical to supplying these products to patients with unmet needs around the world. The new 22,700 m² cell therapy manufacturing facility represents the second significant expansion of BMS' Devens site, which has been developing, producing and testing clinical and commercial medicines for over a decade. The Devens facility creates over 500 new cell therapy jobs. BMS also operates two R&D facilities in Cambridge, Massachusetts and will bring these two sites together into a new building at Cambridge Crossing later in 2023.

CellTrans

The US FDA has approved CellTrans' (IL, USA; www.celltransinc.com) Lantidra, the first allogeneic pancreatic islet cellular therapy made from deceased donor pancreatic cells for the treatment of Type 1 diabetes [45]. Lantidra is approved for the treatment of adults with Type 1 diabetes who are unable to approach target glycated hemoglobin (average blood glucose levels) because of current repeated episodes of severe hypoglycemia despite intensive diabetes management and education.

The safety and effectiveness of Lantidra was evaluated in two non-randomized, single arm studies in which a total of 30 participants with Type 1 diabetes and hypoglycemic unawareness received at least one infusion and a maximum of three infusions. Overall, 21 participants did not need to take insulin for a year or more, with 11 participants not needing insulin for 1–5 years and 10 participants not needing insulin for more than five years. Five participants did not achieve any days of insulin independence.

Kyverna

Kyverna Therapeutics (CA, USA; https://kyvernatx.com), a cell therapy company with the mission of engineering a new class of therapies for serious autoimmune diseases, has announced the US FDA has granted Fast Track designation for KYV-101 for the treatment of patients with refractory lupus nephritis [46]. KYV-101 is a novel anti-CD19 CAR T therapy designed to deplete B cells, including autoreactive B cells, in autoimmune disease patients. Kyverna's phase 1 open-label, multicenter clinical trial of KYV-101 in the USA is actively recruiting patients at multiple sites in the USA [47]. The study is targeted to enroll approximately 9-to-12 patients with lupus nephritis across the US. Kyverna also filed its first EU Clinical Trial Application (CTA) to the Paul Ehrlich Institut in Germany for a parallel phase I/II clinical trial of KYV-101 in lupus nephritis. The first patient was enrolled in trial in the USA a few weeks later [48].

Red light

Arcellx

Arcellx (CA, USA; www.arcellx.com), a biotechnology company reimagining cell therapy through the development of innovative immunotherapies for patients with cancer and other diseases, has announced that following a recent patient death the US FDA has placed a clinical hold on its CART-ddBCMA IND for the treatment of patients with relapsed or refractory multiple myeloma [49,50]. However, the FDA has provided clearance to the company to continue dosing patients who have already undergone lymphodepletion.

Capital market & finances

Acepodia

Acepodia Biotech (CA, USA; www.acepodia.com), a clinical stage biotechnology company developing first-in-class cell therapies with its unique Antibody-Cell Conjugation and allogeneic gamma delta 2 T-cell platforms to address gaps in cancer care, has announced a US$100 million Series D financing [51]. The funds will be used to progress the company's pipeline of enhanced cell therapies for solid tumors and hematologic cancers, including ACE1831 and ACE2016. ACE1831 is an anti-CD20 armed allogeneic gamma delta 2 T-cell therapy currently being studied in a phase 1 trial for patients with non-Hodgkin Lymphoma [52]. ACE 2016 is an anti-EGFR armed allogeneic gamma delta 2 T-cell therapy targeting EGFR-expressing solid tumors.

Calidi

Calidi Biotherapeutics (CA, USA; https://calidibio.com), a clinical-stage biotechnology company that is pioneering the development of allogeneic cell-based delivery of oncolytic viruses, has announced a commitment of US$25 million in Series B funding to advance stem cell-based platforms for the delivery and potentiation of oncolytic viruses to treat cancer [53].

Eureka

Eureka Therapeutics (CA, USA; www.eurekatherapeutics.com), a clinical-stage biotechnology company developing novel T-cell therapies to treat cancer, has announced that the California Institute for Regenerative Medicine (CIRM; CA, USA; www.cirm.ca.gov) awarded the Company a US$10.6 million grant to support its ongoing ARYA-2 phase I study of ET140203 for the treatment of pediatric patients with refractory/relapsed liver cancer, including hepatoblastoma, hepatocellular neoplasm not otherwise specified, and hepatocellular carcinoma [54,55].

Hope Biosciences

A 4-year, nearly US$5 million clinical trial grant awarded to UTHealth Houston (TX, USA; www.uth.edu) by the Department of Defense's Office of Congressionally Directed Medical Research Programs (CDMRP; https://cdmrp.health.mil) to evaluate if intravenously infused Hope Biosciences' (TX, USA; www.hope.bio) autologous, adipose-derived mesenchymal stem cells (HB-adMSCs) reduce chronic neuroinflammatory response to severe traumatic brain injury [56]. Preliminary results from a prior Phase I/IIa, 24-patient study sponsored by Hope Biosciences at UTHealth suggested that repeated intravenous administration of HBadMSCs have the potential of reducing chronic neuroinflammation [57].