Industry Updates from the Field of Stem Cell Research and Regenerative Medicine in April 2021

Abstract

Latest developments in the field of stem cell research and regenerative medicine compiled from publicly available information and press releases from nonacademic institutions in April 2021.

Keywords::

• industry
• regenerative medicine
• stem cells

Business development

Collaboration & licensing agreement: Vertex & Obsidian

Vertex Pharmaceuticals (MA, USA; www.vrtx.com) and Obsidian Therapeutics (MA, USA; www.obsidiantx.com) have entered into a strategic research collaboration and licensing agreement focused on the discovery of novel therapies that regulate gene editing for the treatment of serious diseases [1]. Under the terms of the agreement, Obsidian will use its cytoDRiVE technology to develop novel regulated gene editing therapy candidates for multiple serious diseases. Obsidian grants Vertex the exclusive option to license worldwide rights to candidates discovered and developed under the collaboration. Following Vertex’s exercise of its options, Vertex will be responsible for further preclinical and clinical development and commercialization.

Vertex will pay Obsidian up to US$75 million in upfront payments and research milestones that may be paid during the research term, including an equity investment in Obsidian. Obsidian is eligible to receive up to US$1.3 billion in potential payments based upon the successful achievement of specified research, development, regulatory and commercial milestones across up to five potential programs. In addition, Vertex will pay tiered royalties on future net sales on any products that may result from this collaboration. Specific diseases that are the subject of this collaboration are not disclosed.

Launching new products & services

EryPharm

After 4 years of research and development, EryPharm (France; www.erypharm.com) has entered a pilot production phase and scaleup of cultured red blood cells using hematopoietic stem cells [2,3]. EryPharm is a spin off from Sorbonne University (France; www.sorbonne-universite.fr), created in 2016.

Clinical trials

Agenus

Agenus (MA, USA; https://agenusbio.com), an immuno-oncology company with an extensive pipeline of checkpoint antibodies, cell therapies, adjuvants and vaccines designed to activate immune response to cancers and infections, has announced the dosing of the first cancer patient with agenT-797, an allogeneic invariant natural killer T cell therapy, in a Phase I clinical trial through its subsidiary, AgenTus Therapeutics (UK; www.agentustherapeutics.com) [4]. Invariant natural killer T cells are a unique cell type that combines features of two critical arms of the immune system, T cells (adaptive immunity) and NK cells (innate immunity). The Phase I dose-escalation trial will explore the safety, tolerability and preliminary clinical activity of agenT-797 in patients with relapsed/refractory multiple myeloma.

IMV

IMV (NS, Canada; www.imv-inc.com), a clinical stage biopharmaceutical company pioneering a novel class of cancer immunotherapies, has announced that, following feedback from the US FDA, the company has entered into an agreement with Merck (Germany; www.merck.com) to initiate a Phase IIB clinical trial to evaluate its lead compound, maveropepimut-S (DPX-survivac) in combination with KEYTRUDA^® (pembrolizumab), Merck’s anti-PD-1 therapy, in patients with recurrent/refractory diffuse large B cell lymphoma [5]. The contribution of low dose cyclophosphamide (CPA) as an activator of immune response will also be evaluated in this trial.

The three-arm Phase IIB trial is a randomized, parallel group, Simon two-stage study designed to assess the combination of maveropepimut-S and KEYTRUDA with or without CPA. A third arm will evaluate maveropepimut-S as a single agent. Across the three arms of this study, IMV’s lead compound will be evaluated in up to 150 subjects with recurrent/refractory diffuse large B cell lymphoma who have received at least two prior lines of systemic therapy and who are ineligible or have failed autologous stem cell transplant or CAR T-cell therapy.

Maveropepimut-S is the lead candidate in IMV’s new class of immunotherapy that generates targeted and sustained cancer cell killing capabilities in vivo. Treatments with maveropepimut-S in association with CPA have demonstrated a favorable safety profile across all clinical studies.

Maveropepimut-S, consists of survivin-based peptides formulated in IMV’s proprietary delivery platform (DPX) which is designed to generate a sustained cytotoxic T-cell response against cancer cells presenting survivin peptides on their surface. Survivin, is a tumor-associated antigen, broadly over expressed in most cancer types and plays an essential role in antagonizing cell death, supporting tumor-associated angiogenesis and promoting resistance to chemotherapies. IMV has identified over 20 cancer indications in which survivin can be targeted by maveropepimut-S.

Maveropepimut-S has received Fast Track designation from the FDA as maintenance therapy in advanced ovarian cancer, as well as Orphan Drug designation status from the FDA and the EMA in the ovarian cancer indication.

Tessa Therapeutics

Tessa Therapeutics (Singapore; www.tessacell.com), a clinical stage cell therapy company developing next-generation cancer treatments for hematological malignancies and solid tumors, has enrolled 12 patient pilot cohort of its Phase II trial (https://clinicaltrials.gov; ID: NCT04268706) in relapsed/refractory classical Hodgkin Lymphoma (r/r cHL) [6]. CD30 is a well validated lymphoma target with homogeneous expression in 98% of cHL and a significant proportion of subsets of non-Hodgkin lymphomas. Tessa’s technology modifies the patient’s T cells by introducing a CD30 directed CAR to target and kill cHL. Tessa’s CD30 CAR T-cell therapy, previously induced a complete response in 59% of heavily pretreated r/r cHL patients, with no instance of neurotoxicity or grade 3 cytokine release syndrome. Tessa’s therapy was granted Regenerative Medicine Advanced Therapy designation by the FDA and Priority Medicines (PRIME) designation by EMA.

Regulations, approvals & acquisitions

Green light

Organicell Regenerative Medicine

Organicell Regenerative Medicine (FL, USA; https://organicell.com), a clinical stage biopharmaceutical company dedicated to the development of regenerative therapies, has announced that the FDA has approved the Investigational New Drug application for its lead product, Zofin™, in the treatment of knee osteoarthritis [7]. Zofin is an acellular biologic therapeutic derived from human amniotic fluid. It is manufactured to retain naturally occurring miRNAs, without the addition or combination of any other substance or diluent. This product contains over 300 growth factors, cytokines and chemokines as well as other extracellular vesicles/nanoparticles derived from amniotic stem and epithelial cells. The product contains a mean concentration of 5.24 × 10¹¹ particles/ml with a mean mode size of 125.2 nm. Surface marker analysis confirmed the presence of exosome associated proteins CD63, CD81 and CD9 in addition to high expression of CD133. The completed sequencing revealed 102 commonly expressed miRNA (with a 100-copy expression minimum). Bioinformatics analysis linked 63 miRNAs to 1216 RNA targets. Major players in the pro-inflammatory cytokine cascade found to be targeted by miRNA discovered in Organicell’s product include TNF, IL-6 and IL-8. Additionally, a broader array of pro-inflammatory cytokines is also targeted by the collection of miRNA such as FGF2, IFN-β1, IGF-1, IL-36a, IL-37, TGF-β2, VEGFA, CCL8 and CXCL12. It has been suggested in published research that inhibition or suppression of this pro-inflammatory cytokine cascade may reduce the severity of symptoms associated with elevated immune response. Furthermore, the miRNA was found to target 148 genes associated with immune response. Zofin is currently being tested in a Phase I/II randomized, double blind, placebo trial to evaluate the safety and potential efficacy of intravenous infusion of Zofin for the treatment of moderate to SARS related to COVID-19 infection (https://clinicaltrials.gov; ID: NCT04384445).

Orthofix

Orthofix Medical (TX, USA; www.orthofix.com/), a global medical device company with a spine and extremities focus, has announced the FDA 510(k) clearance of the 3D-printed CONSTRUX™ Mini Ti and the FORZA™ Ti TLIF Spacer Systems both developed with Nanovate™ Technology featuring an optimized design, porosity and surface that allows bone to grow into and through the spacer [8,9]. CONSTRUX Mini Ti is used to enhance anterior cervical discectomy and fusion procedures and it is the first 3D-printed titanium interbody introduced to the market by Orthofix. The FORZA Ti Spacer is used to help optimize transforaminal lumbar interbody fusion procedures.

Vertex & CRISPR Therapeutics

Vertex Pharmaceuticals (MA, USA; www.vrtx.com) and CRISPR Therapeutics (Switzerland; www.crisprtx.com) have announced that the EMA has granted PRIME designation to CTX001, for the treatment of transfusion-dependent beta thalassemia (TDT) [10]. CTX001 was previously granted PRIME designation for the treatment of sickle cell disease (SCD) in 2020. Based on the progress in this program to date, CTX001 has been granted Regenerative Medicine Advanced Therapy, Fast Track, Orphan Drug and Rare Pediatric Disease designations from the FDA for both TDT and SCD. CTX001 has also been granted Orphan Drug Designation from EMA for both TDT and SCD.

CTX001 is being investigated in two ongoing clinical trials as a potential one-time therapy for patients suffering from TDT and severe SCD (https://clinicaltrials.gov; ID: NCT03655678 and NCT03745287). Patients who enroll in these trials will have their own hematopoietic stem and progenitor cells collected from peripheral blood. The patient’s cells will be edited using the CRISPR/Cas9 technology. The edited cells, CTX001, will then be infused back into the patient as part of a stem cell transplant, a process which involves, among other things, a patient being treated with myeloablative busulfan conditioning. Patients will initially be monitored to determine when the edited cells begin to produce mature blood cells, a process known as engraftment. After engraftment, patients will continue to be monitored in a long-term follow-up study to track the impact of CTX001 on multiple measures of disease and for safety (https://clinicaltrials.gov; ID: NCT04208529).

Capital market & finances

Arcellx

Arcellx (MD, USA: https://arcellx.com), a privately held clinical stage biopharmaceutical company, has raised US$115 million in a Series C financing to advance its pipeline of adaptive and controllable cell therapies [11]. The proceeds will support the company’s development of CART-ddBCMA, a BCMA-specific CAR-modified T-cell therapy currently in Phase I and anticipated to begin a pivotal trial in 2022. In addition, the funding will support initiation of clinical trials evaluating ACLX-001 and ACLX-002, cell therapies derived from Arcellx’s uniquely controllable ARC-SparX platform, in multiple myeloma and acute myelogenous leukemia, respectively. This financing follows FDA clearance of Arcellx’s Investigational New Drug for ACLX-001, the first ARC-SparX program to enter clinical trials [12].

ARC-SparX therapies consist of synthetic off-the-shelf SparX proteins which bind the intended antigen and signal autologous engineered immune cells, ARC-T cells, to destroy the tumor target. ARC-T cells cannot recognize the tumor without SparX proteins and can only destroy a diseased cell when attached to a SparX-antigen complex. By adjusting the dose and frequency of SparX administration, the activity of the ARC-T cells can be managed and controlled. Additionally, treatment with alternate SparX proteins can redirect ARC-T cells to different disease antigens to potentially address relapsed and refractory disease due to tumor heterogeneity or antigen escape. Arcellx is developing a collection of antigen-specific SparX proteins to treat a range of cancer and autoimmune diseases in the community setting.

Janux

Janux Therapeutics (CA, USA; www.januxrx.com) has announced the closing of a US$125 million Series B financing [13]. The proceeds of the financing will help support the advancement of Janux’s pipeline of next generation T cell engager immunotherapies, including a PSMA-tumor activated T-cell engager (TRACTr), EGFR-TRACTr and TROP2-TRACTr, into initial proof of concept clinical trials.

Janux’s proprietary TRACTr technology is designed to overcome specific limitations of current T cell immuno-oncology therapies. Although previous therapies utilizing other technologies have displayed substantial antitumor activity, they have been constrained by dose-limiting toxicities, poor pharmacokinetic profiles and attenuated efficacy. Janux’s TRACTr technology is designed to overcome these limitations by integrating tumor-specific activation with crossover pharmacokinetics to produce differentiated T-cell engager therapeutics.

Kadimastem

Kadimastem (Israel; www.kadimastem.com), a clinical stage cell therapy company, has raised NIS22.3 million (US$6.8 million) [14]. As part of the agreement for their investment, participants received shares as well as NIS31.1 million (US$9 million) collectively in options. This brings this financing to a potential total of NIS53.4 million (US$16 million) collective investment. The financing will enable Kadimastem to expedite its research and development programs for both lead indications, AstroRx^® for the treatment of amyotrophic lateral sclerosis and IsletRx, intended to cure Type 1 diabetes. The financing will also enable the company to advance its business development efforts in the US.

Polyneuron & University of Basel

Polyneuron Pharmaceuticals (Switzerland; https://polyneuron.com), a clinical stage developer of a new class of antigen-specific polymers for the treatment of patients with serious autoimmune diseases and their collaborators at the University of Basel (Switzerland; www.unibas.ch) have received a grant from the Swiss Innovation Agency Innosuisse (Switzerland; www.innosuisse.com) to support a project valued at US$1.3 million (Fr 1.2 million) [15]. The project will advance the development of novel injectable glycopolymers to support better ABO-incompatible (ABOi) transplantation patient outcomes. ABOi transplantation, a procedure to transplant solid organs and stem cells without matching ABO blood groups, has been introduced to decrease recipient waiting time and the strongly associated mortality. However, ABOi transplants require powerful immunosuppression to prevent transplant rejection caused by the recipient’s antibodies (isoagglutinins), which can lead to serious infections. The procedures also need cumbersome and time-consuming plasmapheresis or immune apheresis, performed in advance in hospital, to help remove the harmful antibodies and reduce the burden of immunosuppressant drugs.

The grant will be used to leverage Polyneuron’s Antibody-Catch™ platform to engineer novel injectable glycopolymers that mimic blood group antigens to selectively remove the specific, relevant antibodies. Polyneuron and the University of Basel collaborators aim to optimize two antigen-specific glycopolymers for in vitro neutralization and selective elimination of antibodies in a preclinical proof of concept model.

Financial & competing interests disclosure

The author Dusko Ilic has received an honorarium from Future Science Group 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.