Feliza Mirasol is the science editor for 

Feliza Mirasol

TrakCel, a provider of integrated cell and gene therapy (CGT) orchestration solutions, announced on Nov. 12, 2024 that some manufacturers have selected its orchestration platform, OCELLOS, to support the management of five out of seven autologous and matched allogeneic cell therapy products. These products are approved or are expected to be approved in 2024. TrakCel’s technologies enable the precise management, control, and tracking of CGTs.

An IT portal, such as OCELLOS, is needed to successfully navigate the CGT supply chain, as manufacturers require tools to help launch these FDA-approved products and ensure that approved treatment centers (ATCs) can administer the CGT safely and effectively, according to a company press release.

“We’re committed to driving forward patient access to ground-breaking CGTs and are delighted to be supporting a growing number of manufacturers as they navigate the CGT supply chain and successfully launch their product,” said Fiona Withey, PhD, CEO, TrakCel, in the press release. “Commercializing CGT products is a complex and challenging process that requires close collaboration between manufacturers and ATCs. However, as more products are approved, ATCs are concerned this could lead to further proliferation of custom-made orchestration platforms, creating an additional burden on their staff that could potentially hinder the success of future new product launches.”

A list of CGTs approaching regulatory approval by the end of 2024 are listed in a presentation given by The Alliance for Regenerative Medicine (ARM) in August 2024 (1). OCELLOS is a Salesforce-powered solution that was specifically designed for the CGT industry, according to TrackCel, which stated in its press release that the platform aims to deliver a unique therapy process by connecting base modules and configurable forms with real-time visibility showing the progress of each personalized therapy through the supply chain. This workflow is intended to support efficiency in the supply chain and ease collaboration with ATCs.

“Working with our Industry Advancement Board (IAB), we recognize that there is a growing need to standardize on one platform to help foster a consistent approach to capabilities and communication processes, training, workflows, and use of terminology,” Withey stated in the press release. “OCELLOS is a proven technology ready to drive industry-wide standardization and ensure life-enhancing therapies reach the patients that so desperately need them.”

TrackCel also pointed out in its release that it sees continued investment in custom-built IT portals, even as CGT manufacturers are increasingly using OCELLOS. The company stated that these IT portals help facilitate product ordering and patient enrollment as well as efficient orchestration of supply chain activities, including manufacturing and logistics.

“As more CGT products are approved … an increasing number of custom-built platforms could overwhelm clinical site staff and be extremely expensive for each manufacturer to build and support, potentially limiting access to the therapy, and impacting patient safety,” TrackCel warned in its press release.

1. ARM. Sector Snapshot: The Emerging Value of Cell and Gene Therapy. 

alliancerm.org/sector-snapshot-august-2024

Articles

Manufacturers of five autologous or matched allogenic cell therapy products have selected TrakCel's  IT platform, OCELLOS, to orchestrate the administration of these therapies, which are approved or expected to be approved in 2024.

TrakCel’s OCELLOS Platform Selected to Support Treatment Management of Five Upcoming Cell Therapy Products

On Nov. 6, 2024, Johnson & Johnson (J&J) announced that the Medicines and Healthcare products Regulatory Agency (MHRA) of the United Kingdom has granted marketing authorization for Balversa (erdafitinib) to be used as a monotherapy in treating adults with unresectable or metastatic urothelial carcinoma (UC), which is the most common form of bladder cancer (1,2). This approved indication specifically covers eligible patients harboring susceptible fibroblast growth factor receptor 3 (FGFR3) genetic alterations, and who have previously received at least one line of therapy containing a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor in the unresectable or metastatic treatment setting.

MHRA’s authorization is based on results from Cohort 1 of a Phase III study (THOR). The study was randomized, open-label, and spanned multiple clinical treatment centers. The study evaluated the efficacy and safety of erdafitinib (n=136) versus chemotherapy (n=130) in patients with advanced or metastatic UC with select FGFR alterations who have progressed on or after one or two prior treatments, where at least one of those treatments included a PD-1 or PD-L1 inhibitor. The study’s primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR), according to a company press release.

“Patients living with this advanced stage of bladder cancer, and whose tumors harbor FGFR3 alterations, require access to innovative precision therapies that can target the specific characteristics of their disease,” said Professor Alison Birtle, consultant oncologist and honorary clinical professor, Lancashire Teaching Hospitals National Health Service (NHS) Foundation Trust, in the press release. “Unfortunately, until now, there have been limited treatment options available for this group of patients, which may affect not only their prognosis, but their wellbeing and quality of life. Today’s authorization of erdafitinib, a targeted therapy that has been shown to significantly improve overall and progression-free survival for patients with FGFR3 alterations, will come as welcome news to eligible patients, and highlights the importance of integrating biomarker testing into the treatment pathway for people with urothelial cancer, so that genetic alterations such as FGFR3 can be detected as early as possible.”

Erdafitinib is administered orally as a once-daily, FGFR kinase inhibitor. It works by inhibiting the activity of FGFR3 alterations in cancer cells and has demonstrated an ability to extend overall survival compared to chemotherapy in the second-line setting (3).

In June 2023, the Phase III study (THOR) was stopped based on the recommendation of an independent data safety monitoring committee, following a review of efficacy and safety data of the study at interim analysis (3). All patients who were randomized to chemotherapy (docetaxel or vinflunine) were offered an opportunity to receive erdafitinib as crossover therapy, and results at the data cut-off timepoint showed that median OS of over one year was achieved in those patients receiving erdafitinib. These results marked a significant improvement compared to the patients in the chemotherapy arm (12.1 months vs. 7.8 months; hazard ratio, 0.64; 95% confidence interval, 0.44 to 0.93; P=0.005) (1).

Moreover, treatment with erdafitinib showed an improvement in median PFS compared to chemotherapy of 5.6 months versus 2.7 months and a confirmed ORR of 48 out of 136 patients (35.3%) versus 11 out of 130 patients (8.5%) (1).

“We are delighted that the MHRA has recognized the value that erdafitinib could bring to eligible patients with metastatic urothelial cancer,” said John Fleming, country medical director, Johnson & Johnson Innovative Medicine UK, in the release. “This milestone reflects J&J’s long-standing dedication to getting in front of cancer and delivering the most innovative precision therapies to patients in need. We look forward to progressing with HTA [health technology assessment] submissions for erdafitinib in the coming months, with the view to enabling eligible patients to access erdafitinib through the NHS as soon as possible.”

In the UK, approximately 10,500 people are diagnosed with bladder cancer each year, equating to 29 people every day (4). Of those diagnosed with advanced or metastatic bladder cancer, roughly 20% have FGFR3 alterations, which can drive the growth of cancer cells (5).

1. MHRA. Electronic Medicines Compendium, Balversa Summary of Product Characteristics. 

 (accessed November 6, 2024).
2. Leslie, S.W.; Soon-Sutton, T. L.; Aeddula, N. R. Bladder Cancer. In 

; StatPearls Publishing, Aug. 15, 2024.
3. Loriot, Y.; Matsubara, N.; Park, S. H.; et al. Erdafitinib or Chemotherapy in Advanced or Metastatic Urothelial Carcinoma. 

 (21),1961–1971.
4. Cancer Research UK. Bladder Cancer Statistics. 

cancerresearchuk.org/health-professional/cancer-statistics/statistics-bycancer-type/bladder-cancer

 (accessed Nov. 6, 2024).
5. Xiao, J. F.; Caliri, A. W.; Duex, J. E.; Theodorescu, D. Targetable Pathways in Advanced Bladder Cancer: FGFR Signaling. 

Balversa (erdafitinib) marks the first and only bladder cancer therapy to target FGFR3 alterations, with a demonstrated increase in overall survival from 7.8 months to 12.1 months. 

J&J’s Balversa Gains MHRA Marketing Authorization as Monotherapy for Bladder Cancer

Aditum Bio announced on Nov. 7, 2024 that it has formed a new company with Leads Biolabs, called Oblenio Bio. Oblenio Bio was formed in conjunction with an exclusive option and license agreement that the companies have entered into for the development of LBL-051, a first-in-class CD19xB-cell maturation antigen (BCMA)xCD3 tri-specific T-cell engager antibody, for treating autoimmune diseases. A US-based biotech venture firm, Aditum Bio will fund Oblenio Bio. In collaboration with Leads Biolabs, a clinical-stage biotechnology company based in Nanjing, China, the companies aim to rapidly progress LBL-051 to clinical studies.

Under the agreement, Leads Biolabs will grant the newly formed Oblenio Bio an exclusive option to develop, manufacture, and commercialize LBL-051 worldwide. In return, Leads Biolabs is eligible to receive up to $35 million in upfront and near-term payments, $579 million in development, regulatory, and commercialization milestone payments, and royalties on sales. Leads Biolabs is also entitled to receive an equity stake in Oblenio Bio.

“By targeting both CD19 and BCMA in autoimmune disorders, LBL-051 has the potential to achieve a complete immune reset and superior efficacy and durability, compared to single targeting of either CD19 or BCMA alone”, said Joe Jimenez, co-founder and managing director of Aditum Bio, in the release.

Based on recent clinical data (1,2), CD19 and BCMA targeted therapies have shown compelling efficacy in difficult-to-treat autoimmune diseases, according to a company press release. Despite the promising results, however, there remains a continued unmet need for increased efficacy and durability; thus, by targeting both CD19 and BCMA, LBL-051 offers the potential to deliver stronger and more durable responses. The therapeutic is designed to deplete a broader range of pathological B-cell populations across a wide spectrum of antibody-mediated autoimmune diseases, the companies stated in the press release.

LBL-051 is a novel tri-specific T-cell engager developed from the LeadsBody Platform. Each target binding domain—CD19, BCMA, and CD3—was engineered for the express intent of enhancing safety while optimizing efficacy. These domains have been finely tuned to enhance their individual relative potency.

“LBL-051 offers a differentiated approach to treating certain autoimmune conditions and has the potential to be a Pipeline in a Product. We are pleased to establish this partnership with the high caliber team at Aditum to bring this innovative therapy to patients around the world,” said Xiaoqiang Kang, MD, PhD, founder, chairman, and CEO of Leads Biolabs, in the release.

Oblenio Bio marks the thirteenth company launched by Aditum Bio as part of the company’s missioin to give large patient populations access to important medicines. Aditum Bio fosters an incubator model, which aims to speed time-to-market and focuses on the translational phase of drug development. The company also in-licenses promising drug candidates and spins out individual companies dedicated to progressing each candidate through to early clinical trials.

Leads Biolabs focuses on the discovery and development of innovative therapies that address significant unmet medical needs in oncology, autoimmune diseases, metabolic disorders, and other serious conditions. The company’s R&D pipeline includes more than 20 novel candidates across various modalities, including monoclonal antibodies, multi-specific antibodies, T-cell engagers, and antibody-drug conjugates.

1. Zhang, W.; Feng, J.; Cinquina, A.; et al. Treatment of Systemic Lupus Erythematosus using BCMA-CD19 Compound CAR

, 2120–2123. DOI: 10.1007/s12015-021-10251-6
2. Wang, W.; He, S.; Zhang, W.; et al. BCMA-CD19 Compound CAR T Cells for Systemic Lupus Erythematosus: A Phase 1 Open-label Clinical Trial. 

In the collaboration, the new company, Oblenio Bio, has been granted an exclusive option to license LBL-051, a tri-specific T-cell engager antibody, from Leads Biolabs.

Oblenio Bio Created by Aditum Bio and Leads Biolabs to Develop Therapeutic Antibody for Treating Autoimmune Disorders

On Oct. 30, 2024, Lonza's Synaffix announced that it has licensed its antibody-drug conjugate (ADC) technology to BigHat Biosciences (BigHat), a US-based biotech company. BigHat will combine the Synaffix technology with its machine learning (ML) antibody design platform to develop a new ADC pipeline program.

Under the agreement, BigHat will receive target-specific access to Synaffix’s late clinical-stage, site-specific ADC technology platform. This platform enables transformation of antibodies into proprietary, best-in-class ADC products. Lonza’s acquisition of Synaffix in June 2023 (1) means that BigHat also gains access to Lonza’s DNA-to-investigational new drug (IND) ADC offering. This DNA-to-IND offering enables drug developers to receive all necessary current good manufacturing practice (CGMP)/non-CGMP ADC batches leading up to the first clinical trial. The service is housed under a single quality system that encompasses all critical development and manufacturing activities, including antibody production, bioconjugation, and drug product filling.

“The ADC space continues to develop and evolve, and our collaboration with BigHat exemplifies the continued strength and appeal of our best-in-class ADC technology. We are excited to be at the forefront of next-generation ADC R&D by joining forces with BigHat and its AI [artificial intelligence]/ML-enabled antibody discovery and development platform. BigHat is the ideal partner for Synaffix to collaborate with. We look forward to supporting BigHat with every step in the ADC development and manufacturing process under the Lonza umbrella,” said Peter van de Sande, head of Synaffix, in a company press release.

Milliner, which is BigHat’s AI/ML-powered antibody design platform, works by integrating a synthetic biology-based high-speed wet lab with state-of-the-art ML technologies into a full-stack antibody discovery and engineering platform. This platform is used to engineer antibodies with more complex functions and better biophysical properties. Using this approach reduces the difficulty of designing antibodies and other therapeutic proteins when developers look to tackle conditions ranging from chronic illness to life-threatening disease. The platform also offers significant speed to reaching candidate discovery and validation.

“We are pleased to announce this collaboration with BigHat for its next-gen ADC molecule, which shows how drug developers can benefit from a fully integrated suite of services across our Biologics division. The Lonza network has continued to adapt to the evolving ADC landscape, including the recent addition of a highly potent vial fill capability at our Stein (CH) [Switzerland] facility. This dedicated ADC drug product capacity expansion completes our offer for comprehensive, end-to-end development and manufacturing services for ADCs, simplifying the path from DNA-to-IND and beyond for our customers,” Jean-Christophe Hyvert, president, Biologics, Lonza, said in the release.

Through this collaboration with Synaffix/Lonza, BigHat intends to advance its next-gen ADC program. BigHat’s ADC program is at the IND-enabling stage and is on track to be the company’s first clinical-stage program. According to the press release, BigHat’s next-gen ADC was optimized using the Milliner platform. It is designed for maximum payload delivery to tumor cells and with optimal drug-like-properties. Incorporating Synaffix's ADC technologies, such as GlycoConnect, HydraSpace, and toxSYN, BigHat expects to further improve the safety and efficacy of its next-gen ADC.

"BigHat is leveraging our AI-driven antibody design platform, Milliner, to develop advanced biologics that provide safer and more effective treatments for difficult-to-treat cancers. We are excited to combine Synaffix’s conjugation and linker-payload technologies with our custom-designed antibody to create a next-generation ADC for patients with high unmet medical need," said Mark DePristo, CEO, BigHat Biosciences, in the release.

1. Lonza. Lonza to Acquire Synaffix and Strengthen Antibody-Drug Conjugates Offering. Press Release. June 1, 2023.

Synaffix, a Lonza company, has licensed its ADC technology to BigHat Biosciences to be combined with the latter's ML design platform to develop new ADCs

Synaffix, a Lonza Company, Collaborates with BigHat Biosciences on ADCs Designed Using Machine Learning

Gefion, a new artificial intelligence (AI) supercomputer built on an AI data center infrastructure known as NVIDIA DGX SuperPOD (1), is now operational in Copenhagen, Denmark, the Novo Nordisk Foundation announced on Oct. 23, 2024. The supercomputer was launched at an event in Copenhagen, where it was symbolically “turned on” by His Majesty King Frederik X of Denmark; Jensen Huang, founder and CEO of NVIDIA, a US-based supercomputing company; and Nadia Carlsten, CEO of the Danish Centre for AI Innovation (DCAI).

Following its launch, Gefion is being readied for customers, beginning with a pilot phase in which select customers interested in using AI will use it to accelerate innovation in many areas, from quantum computing to drug discovery to societal challenges, such as the transition to green energy.

“Gefion provides our Danish enterprises with entirely new opportunities,” said Morten Bødskov, the Minister for Industry, Business, and Financial Affairs, Denmark, in a press release. “Gefion will drive the advancement of the green transition, enable tailor-made solutions, and strengthen the competitive standing of our companies in the global market. In a time of heightened international competition, this supercomputer acts as a vital enabler for advancing Danish businesses into the future. This ground-breaking technology represents an important opportunity for Danish companies and researchers to develop innovative solutions to future challenges.”

A public–private partnership between the Novo Nordisk Foundation and the Export and Investment Fund of Denmark (EIFO) resulted in the establishment of the new supercomputer. This partnership funded and established DCAI, a new company that owns and will operate Gefion.

“It’s a remarkable achievement that it has taken only six months from announcement to completion of this complex state-of-the-art supercomputer,” said Carlsten. “I am extremely proud of the team that came together and collaborated to turn this vision into a reality, delivering a leading capability that is now ready for customers to start testing new use cases. Gefion is the game-changer that many innovators had been waiting for.”

Huang added in the release, “Denmark recognizes that to innovate in AI, the most impactful technology of our time, it must foster a domestic AI infrastructure and ecosystem. The Gefion supercomputer will supercharge the scientists of Denmark with local AI computing infrastructure to drive advancements in life sciences, climate research, and quantum computing.”

Gefion is powered by 1,528 graphic processing units (GPUs) (NVIDIA H100 Tensor Core GPUs) and is interconnected using networking (NVIDIA Quantum-2 InfiniBand). According to the press release, “Denmark up to now had no GPU-accelerated supercomputers, and a thorough consulting process with relevant stakeholders across the country had identified access to computing power as a key roadblock to progress in Denmark’s otherwise thriving AI-based research ecosystem.”

Digital Realty, a global data center provider, hosts the supercomputer in an AI-ready data center facility in Denmark, which is designed and built sustainably, running on 100% renewable energy, according to the press release. Gefion was assembled and installed by Eviden, a European-based high-performance computing company.

In addition to the Novo Nordisk Foundation’s funding, EIFO contributed DKK 100 million (US$15 million) and owns a 15% minority stake in DCAI.

“Establishing Gefion is a milestone, and it fits very well with the Novo Nordisk Foundation’s vision of improving people’s health and the sustainability of society and the planet, as it creates new opportunities and can accelerate finding new solutions to pressing challenges,” said Mads Krogsgaard Thomsen, CEO of the Novo Nordisk Foundation, in the release. “In the future, we must cooperate even more with exceptional partners from all over the world if we are to solve the enormous challenges facing not only our own countries but the planet.”

Researchers will have the opportunity to engage with expert teams from NVIDIA in selected flagship project areas to co-develop solutions to complex problems. These areas include pharmaceuticals and biotechnology research, accelerating the green transition; and developing fault-tolerant (i.e., error-free) quantum computing using an open-source hybrid quantum computing platform (NVIDIA CUDA-Q).

With DKK 600 million (US$87.4 million) in funding from the Novo Nordisk Foundation, the new supercomputer offers the potential to accelerate innovation in drug discovery.

Denmark’s First AI Supercomputer for Drug Discovery Now Operational Under Novo Nordisk Foundation Commitment

ViaNautis Bio (ViaNautis), a UK-based biotechnology company specializing in delivering targeted genetic nanomedicines, announced on Oct. 28, 2024 that it has entered a collaboration agreement with Eli Lilly and Company (Lilly) in which Lilly will use ViaNautis’ proprietary polyNaut platform to develop precision therapeutics carrying genetic cargos. The collaboration aims to precisely deliver these therapeutics to prioritized tissues to address significant unmet medical needs.

Under the agreement, Lilly will pay ViaNautis an initial upfront payment with the short-term potential of making additional payments, including research-based milestones. ViaNautis is eligible to receive further milestones and royalties contingent upon specific cargo-loaded polyNaut-based products entering clinical development and reaching and reaching commercialization.

“This collaboration with Lilly is a testament to our polyNaut platform, which is also driving a highly differentiated emerging pipeline for severe life-limiting diseases. Combining our scientific know-how to precisely deliver genetic nanomedicines targeting difficult-to-reach sites, with Lilly’s extensive drug development and commercialization expertise will accelerate the creation of novel therapies to improve patient outcomes,” said Francesca Crawford, PhD, co-founder of ViaNautis, in a company press release.

The company’s proprietary polyNaut nanovesicles are designed to precisely target specific tissues and cell types to deliver genetic materials. The technology aims to improve the current delivery of genetic medicines and hold the potential to transform treatment for various diseases, according to the company in the press release.

“I am very excited about our collaboration with Lilly to develop novel genetic medicines for patients in need. I want to thank [Crawford] and the team for their hard work in getting to this key milestone, and I look forward to working with Lilly to accelerate our shared vision of delivering targeted genetic medicines,” said Adi Hoess, MD, PhD, chief executive officer of ViaNautis, in the release. The company is currently working on a pipeline of therapeutics in the central nervous system and cystic fibrosis disease fields (1).

Nanovesicles are being researched as alternatives to extracellular vesicles (EVs) for various applications, including drug delivery. As mediators of intercellular communication, EVs have gained growing interest from researchers for their potential use in the field of regenerative medicines or as a drug delivery vehicle. However, because EVs are derived from stem cells or progenitor cells, their use is limited primarily due to a lack of efficient and scalable production methods (2).

As a result, researchers are turning to nanovesicles, particularly biofabricated cell-derived nanovesicles, as an alternative to EVs that are offer scalable, efficient, and cost-effective production (2). Meanwhile, further research has been underway to develop and test simplified and rapid production methods for cell-derived nanovesicles that offer advantages over traditional methods in terms of yield and cost-effectiveness (3), which are anticipated to offer new approaches to therapeutic drug delivery.

 (accessed Oct. 30, 2024).
2. Ilahibaks, N. F.; Lei, Z.; Mol, E. A.; et al. Biofabrication of Cell-Derived Nanovesicles: A Potential Alternative to Extracellular Vesicles for Regenerative Medicine. 

 (12),1509. DOI: 10.3390/cells8121509
3. Goh, W. J.; Zou, S.; Ong, W. Y.; et al. Bioinspired Cell-Derived Nanovesicles versus Exosomes as Drug Delivery Systems: a Cost-Effective Alternative. 

The partnership will use ViaNautis’ proprietary polyNaut technology platform to develop genetic medicines that can precisely target tissue types.