Industry updates from the field of stem cell research and regenerative medicine in November 2022

Business development

Collaboration agreement: Cartherics & Peter Mac

Cartherics (Australia; https://cartherics.com) and the Peter MacCallum Cancer Centre (Australia; www.petermac.org) have entered into a Collaborative Development Program Agreement to develop Cartherics’ proprietary autologous chimeric antigen receptor (CAR)-T cell therapy (CTH-001) for the treatment of cutaneous T-cell lymphoma (CTCL) [1]. CTH-001 is a Cartherics’ proprietary product candidate based on autologous CAR-T cells targeting TAG-72. Cartherics’ researchers identified that TAG-72 is present on the aberrant T cells associated with CTCL but is essentially absent from normal T cells. Non malignant T cells obtained from the blood of the CTCL patient to be treated are reprogrammed to bind specifically to the tumor cells expressing TAG-72. Upon infusion into the patient, the CTH-001 CAR-T cells are expected to destroy the CTCL-associated malignant T cells.

Collaboration agreement: Cynata & LUMC

Expected to commence in 2023, Cynata (Australia; www.cynata.com) along with the transplant center of the Leiden University Medical Center (LUMC; The Netherlands; www.universiteitleiden.nl/en/medicine-lumc), will collaborate on a new clinical trial in patients who have received a kidney transplant [2]. The trial will investigate Cynata’s induced pluripotent stem cell derived mesenchymal stem/stromal cells as a treatment for renal graft rejection and to potentially reduce the requirement for anti rejection drugs.

Partnership agreement: ElevateBio & Affini-T

ElevateBio (MA, USA; www.elevatebio.com), a technology driven company focused on powering transformative cell and gene therapies, and Affini-T Therapeutics (MA, USA; https://affinittx.com), a biotechnology company unlocking the power of T cells against oncogenic driver mutations, have announced a partnership to advance Affini-T’s engineered T cell receptor-T therapies focused on KRAS, one of the most prevalent oncogenic driver mutations in solid tumor cancers [3]. Affini-T will leverage ElevateBio BaseCamp’s LentiPeak™ lentiviral vector technology platform and cell therapy production capabilities to advance its investigational oncogenic driver programs into clinical development. ElevateBio BaseCamp is a purpose built viral vector and cell therapy center of excellence with end-to-end process development and current (cGMP) manufacturing capabilities for research, clinical and commercial cell and gene therapies and regenerative medicines.

Launching new products, services…

bit.bio

bit.bio (UK; www.bit.bio) has announced three additions to its product portfolio: ioGlutamatergic Neurons MAPT N279K™ and ioGlutamatergic Neurons MAPT P301S™ disease models, and early access to its ioGABAergic Neurons™ [4]. This announcement expands the company’s CNS portfolio to four disease models and three cell types. bit.bio’s cell products are reprogrammed from human induced pluripotent stem cells using the company’s proprietary precision reprogramming technology opti-ox™. ioGlutamatergic Neurons MAPT N279K and ioGlutamatergic Neurons MAPT P301S each contain different mutations in the MAPT gene commonly observed in frontotemporal dementia (FTD) patients. FTD is the second leading cause of early onset dementia following Alzheimer’s disease. Patients with FTD suffer from behavior and personality changes and lose their ability to perform daily tasks. About a third of FTD cases are hereditary and have been linked to mutations in the MAPT gene.

FUJIFILM

FUJIFILM Corporation (Japan; www.fujifilm.com) has announced a US$188 million investment to establish a cell culture media manufacturing facility in Research Triangle Park, NC, USA [5]. The new site will be operated by FUJIFILM Irvine Scientific (CA, USA; www.irvinesci.com), a subsidiary of FUJIFILM Corporation. The new facility is planned to ensure that FUJIFILM Irvine Scientific can meet increasing market demands for high quality cell culture media solutions.

The state-of-the-art manufacturing facility will be over 23,000 m² (250,000 sq. ft.) and located across 0.26 km² (64 acres) in Research Triangle Park. The site will support cGMP manufacturing of animal component-free, dry powder and liquid media, adding additional production capacity for FUJIFILM Irvine Scientific of 800,000 kg/year for dry powder, 3,300,000 l/year for liquid and 40,000 l/day of water for injection.

Achievements

Biogennix

Biogennix (CA, USA; http://biogennix.com), an advanced bone regeneration technology company, has announced that its DirectCell^® advanced bone grafting system has been used in more than 1000 cases as of this quarter [6]. The DirectCell System includes an advanced synthetic bone graft material with properties that enhance cellular bone formation, along with novel instrumentation engineered to harvest high concentrations of patient stem cells. This provides surgeons an optimal biological graft that jumpstarts the bone regeneration process. The DirectCell System also provides surgeons two methods of collecting bone marrow derived stem cells, either through the harvesting of stem cell aspirate, which has significantly higher stem cell counts compared with standard bone marrow aspirate, or marrow-rich autograft dowels. Together the technologies within the DirectCell System allow surgeons to leverage both advanced synthetic material technology and the power of a patient’s own stem cells. The DirectCell System is available with Biogennix’s bioactive bone grafts, Agilon Moldable or Agilon Strip. Agilon^® products are based on Biogennix’s unique TrelCor^® technology that contains a nanocrystalline hydroxycarbanoapatite graft surface and offers dual stage resorption through a unique biphasic composition, which together actively promote bone regeneration.

ElevateBio

ElevateBio (MA, USA; www.elevatebio.com), a technology driven company focused on powering transformative cell and gene therapies, has unveiled proprietary LentiPeak lentiviral vector platform. LentiPeak is a serum-free, suspension-based, scalable production platform that has demonstrated high volumetric productivity of therapeutically relevant vector yields that meet regulatory guidelines [7]. LentiPeak will enable efficient transition for cell and gene therapies from preclinical stage through clinical development and commercialization with accelerated timelines and reduced manufacturing costs.

The LentiPeak platform leverages ElevateBio BaseCamp’s end-to-end process and analytical development expertise and scientific leadership and builds upon the company’s cGMP manufacturing capabilities for research, clinical and commercial cell and gene therapies and regenerative medicines.

Namocell

Namocell (CA, USA; www.namocell.com), a Bio-Techne Corporation Company (MN, USA; www.bio-techne.com), has published a single-cell cloning workflow study using the Namocell™ Single Cell Dispenser [8,9]. This publication outlines a robust and scalable workflow for cloning human pluripotent stem cells that maximizes the viability of the cells. The use of the low pressure microfluidic Namocell Single Cell Dispenser ensured gentle and rapid dispensing of single cells into 96- and 384-well plates, while the fast-acting chroman 1, emricasan, polyamines and transISRIB (CEPT) cocktail minimized cellular stress and maintained cell structure and function immediately after single cell isolation. The relative ease, scalability and robustness of this workflow was identified to boost gene editing in human pluripotent stem cells supporting a wide range of applications, such as cell line development (e.g., reporter and isogenic cell lines), disease modeling and regenerative medicine. Single Cell Dispenser portfolio includes Pala™, a 2-laser system with up to 11 fluorescent detection channels and Hana™, a single-laser system with two fluorescent detection channels. Both instruments are capable of sorting and dispensing cells in a single step into a 96-well plate in 1 min and a 384-well plate in 6 min, while being gentle to the cells and preserving cell viability and integrity. They are very easy to operate and require no calibration or flow cytometry experience. Single cell dispensers utilize single-use cell cartridges to deliver cell sorting and dispensing capabilities, achieve high cell recovery and prevent cross-contamination.

Clinical trials

Pluripotent stem cells

Lineage cell threapeutics

Lineage Cell Therapeutics (CA, USA; https://lineagecell.com), a clinical-stage biotechnology company developing allogeneic cell therapies for unmet medical needs, has announced that its partner Genentech (CA, USA; www.gene.com), a member of the Roche Group (Switzerland; www.roche.com), had launched a phase IIa, multicenter, open-label, single-arm clinical study of RG6501 (OpRegen), a retinal pigment epithelial cell therapy [10,11]. The study is intended to optimize subretinal surgical delivery and evaluate the safety and activity of OpRegen in patients with geographic atrophy secondary to age related macular degeneration. Approximately 30 and up to 60 patients may be enrolled across multiple sites and will receive OpRegen administered as a single subretinal injection to one eye with impaired vision. Study treatment will consist of a single subretinal injection of OpRegen at a dose of up to approximately 200,000 cells delivered to target areas of GA in the study eye.

The primary objectives of the study are to evaluate: the proportion of patients with subretinal surgical delivery of OpRegen to target regions under the retina; and to evaluate the safety of subretinal surgical delivery of OpRegen as measured by the incidence and severity of procedure-related adverse events at 3 months following surgery. A key secondary objective is to evaluate the proportion of patients with qualitative improvement in retinal structure, as determined by optical coherence tomography (SD-OCT) imaging, within 3 months following surgery. RG6501 (OpRegen) is currently being developed under an exclusive worldwide collaboration between Lineage, Roche and Genentech.

Hematopoietic stem cells

EdiGene

EdiGene (China; www.edigene.com), a clinical-stage company focused on translating gene-editing technologies into transformative genetic medicines for patients with significant unmet medical needs, has completed the last patient dosing in Phase I clinical trial of ET-01, its investigational gene-editing hematopoietic stem cell therapy for transfusion dependent β-thalassemia [12,13]. ET-01 is an autologous CD34⁺ hematopoietic stem/progenitor cell with the erythroid-specific enhancer of the BCL11A gene modified by CRISPR/Cas9. It is the first gene-editing experimental therapy and the first hematopoietic stem cell experimental therapy with Investigational New Drug application approval by the National Medical Products Administration (NMPA; China; http://english.nmpa.gov.cn). The phase I clinical trial is a multicenter, open-label, single-arm study to assess the safety and efficacy of a single dose of ET-01 in transfusion dependent β-thalassemia patients with eight subjects enrolled.

Other

Editas

Editas Medicine (MA, USA; www.editasmedicine.com), a clinical-stage genome-editing company, has announced clinical data from the phase I/II BRILLIANCE trial of EDIT-101, an in vivo CRISPR/Cas9 genome editing medicine [14,15]. EDIT-101 is under development for the treatment of blindness due to Leber congenital amaurosis 10 (LCA10, a CEP290-related retinal degenerative disorder) and is designed to repair the CEP290 IVS26 mutant allele that impacts approximately 1500 LCA10 patients in the USA. There is no effective treatment currently available for this serious, rare disease. The BRILLIANCE update includes safety and efficacy data from all 14 patients treated in the study to date, which includes 12 adult patients and two pediatric patients. Three out of 14 treated subjects met a responder threshold having experienced clinically meaningful improvements in best corrected visual acuity (LogMAR >0.3) and demonstrated consistent improvements in two of the following three additional end points: full field sensitivity test, visual function navigation course or the visual function quality of life. An examination of baseline characteristics of the treatment responder patients revealed that two of the three responders were homozygous for IVS26 cryptic splice site mutation (2/2; 100% of the homozygous patients treated). No other baseline characteristics that could pre-select a responder patient population were identified in the BRILLIANCE dataset. EDIT-101 was tolerated with no ocular serious adverse events or dose-limiting toxicities observed. Most adverse events were mild and expected for subretinal delivery.

Since LCA10 patients homozygous for CEP290 IVS26 mutation represent an estimated population of approximately 300 in the US, the Company will not progress this program independently, and will seek to identify a collaboration partner to continue the development of EDIT-101. As a result, Editas Medicine is pausing further enrollment in the BRILLIANCE trial and will continue long term follow-up of all patients who have been treated to date.

Priothera

Priothera (Ireland; https://priothera.com), a late-clinical stage biotechnology company, has announced positive data from the phase Ib clinical trial evaluating mocravimod in allogeneic hematopoietic cell transplantation (allo-HCT) patients [16].

The study assessed the safety and tolerability of mocravimod (also known as KRP203), a synthetic, S1PR modulator, in patients undergoing allo-HCT for hematological malignancies [17]. The secondary objectives were to determine the pharmacokinetic profile of mocravimod in this patient group as well as to assess GvHD-free, relapse-free survival at 6 months after last treatment.

The study found that mocravimod can safely be added to standard treatment regimens in patients with hematological malignancies requiring allo-HCT. CD4⁺ T cells were more sensitive to mocravimod treatment than CD8⁺ T cells. Mocravimod resulted in a significant reduction of circulating lymphocyte numbers and had no negative impact on engraftment and transplant outcomes.

A global phase IIb/III study assessing the efficacy and safety of mocravimod as an adjunctive and maintenance therapy in acute myeloid leukemia patients undergoing allo-HCT is planned to start in the coming months [18].

Regulations, approvals, acquisitions…

Green light

Aleta bio

Aleta Biotherapeutics (MA, USA; www.aletabio.com), a privately held immuno-oncology company with novel biologic CAR T engagers that work in synergy with cell therapies to improve outcomes for patients, has announced that the UK Medicines and Healthcare products Regulatory Agency (MHRA; UK; www.gov.uk/government/organisations/medicines-and-healthcare-products-regulatory-agency) has granted an Innovation Passport under the Innovative Licensing and Access Pathway for CAR T-cell therapy Engager candidate ALETA-001 for the treatment of patients suffering from the B-cell malignancies, non-Hodgkin lymphoma a and acute lymphoblastic leukemia and who have failed to respond or have relapsed post-CD19 CAR T-cell therapy [19]. ALETA-001 is expected to enter clinical development in 2023 with Cancer Research UK’s Center for Drug Development sponsoring and conducting a phase I/IIa clinical trial.

The Innovation Passport is the first step in the Innovative Licensing and Access Pathway process, triggering the MHRA and its partner agencies, including The All Wales Therapeutics and Toxicology Centre (AWTTC; UK; https://awttc.nhs.wales), National Institute for Health and Care Excellence (NICE; UK; www.nice.org.uk), and the Scottish Medicines Consortium (SMC; UK; www.scottishmedicines.org.uk), to chart a roadmap for regulatory and development milestones to enable faster patient access to medicines in the UK. To receive an Innovation Passport, a medicine must address conditions that are life-threatening or seriously debilitating, and there must be an existing significant patient or public health need.

Capital market & finances

AgeX

AgeX Therapeutics (CA, USA; www.agexinc.com), a biotechnology company developing therapeutics for human aging and regeneration, has received a notification from the NYSE American (the ‘Exchange’) that the Exchange has accepted a revised listing compliance plan from AgeX and has granted AgeX an extension of time to regain compliance with the Exchange’s continued listing standards as set forth in Section 1003(a)(i) and (ii) of the Exchange Company Guide by increasing its stockholders equity to not less than US$4,000,000 [20]. The Exchange staff will periodically review AgeX’s adherence to the plan milestones. If AgeX is not in compliance with the continued listing standards by 17 May 2023, or if AgeX does not make progress consistent with the plan during the plan period, the Exchange will initiate delisting proceedings as appropriate. AgeX intends to make arrangements to have its common stock quoted on an electronic interdealer quotation system if its common stock is delisted from the Exchange.

Hemanext

Hemanext (MA, USA; https://hemanext.com), a blood processing, storage and transfusion technology company, has announced the successful first close of its Series B fundraising round [21]. Taken together with the exercise of outstanding warrants, this close brings an additional US$18 million of equity capital from noted global private investors with deep finance and healthcare expertise. To date, the company has raised approximately US$130 million, inclusive of US$8 million in grant funding from the NIH.

Novadip

Novadip Biosciences (Belgium; https://novadip.com), a clinical-stage biopharmaceutical company developing a new class of regenerative tissue products to accelerate healing of large bone defects and injuries in a single treatment, has raised an additional US $43 (€40) million in a Series B equity round and non dilutive funding [22]. The funding will accelerate the clinical development of two of Novadip’s investigational adipose stem cell-derived tissue regeneration products: NVD-X3, an allogeneic therapeutic that can provide accelerated, durable bone union in spinal fusion procedures and non healing fractures and NVD-003, an autologous bone engraftment product designed to provide a single treatment cure for patients with critical size bone defects such as congenital pseudoarthrosis of the tibia.