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Tuesday 3rd December – Day 1 Main Conference - GMT (Greenwich Mean Time, GMTZ)
- Lindsay Davies - Chief Scientific Officer, NextCell Pharma
- The forgotten millions: overview of the immense unmet need facing the rare disease community.
- How investment fuels recent breakthroughs, especially within cell & gene therapy
- The necessity of partnerships between researchers, investors, the industry, and patient advocacy groups to transform healthcare for rare diseases.
- Catriona Crombie - Associate Director for Technology Transfer and Rare Disease Challenge Lead, LifeArc
- Gerardo Santiago Toledo - Director, Cell Process Development, Autolus Therapeutics
NextCell Pharma is a clinical cell therapy company working in the autoimmune and inflammatory disease space. Their lead drug candidate, ProTrans is comprised of umbilical cord mesenchymal stromal cells (UC-MSC) selected using the company’s proprietary selection algorithm and pooled to generate the cryopreserved therapy. ProTrans has been used in Phase I and II trials for the treatment of type 1 diabetes and in severe lung hyperinflammation due to viral pneumonia.
Dr Davies is the Chief Scientific Officer for NextCell Pharma and will present the company’s current clinical portfolio for type 1 diabetes. The company has conducted a Phase I open label dose-escalation study with a primary endpoint of safety, as well as a Phase II double-blinded, randomised and placebo-controlled study with a primary endpoint of Δ-change in C-peptide area under the curve for a mixed meal tolerance test at 1 year following ProTrans/placebo infusion compared with baseline performance prior to treatment.
Dr Davies will share data demonstrating the efficacy of ProTrans treatment on preserving endogenous insulin production in newly diagnosed type 1 diabetes patients and the company’s long-term follow-up indicating that a single infusion of ProTrans results in a disease altering effect, with a slowing of disease progression for >3.5 years.
The company is now participating in a Phase II paediatric trial for the treatment of newly diagnosed diabetes in individuals aged 7-21. An update on the current trial status and vision for the future will be discussed as part of this presentation.
- Lindsay Davies - Chief Scientific Officer, NextCell Pharma
Practical solutions to achieve a 'get it right the first time' bioprocess, from the experience of running a multi-national, multi-product clinical cell therapy manufacturing portfolio. Early drug development decisions are critical to the commercialisation pathway, and understanding the healthcare landscape, treatment setting and infrastructure are necessary to design a competent CMC strategy for growth. However, drug manufacturing to meet the scale and agility necessary to support clinic-driven development is highly challenging. Real-world solutions to starting material selection, and technology intensification for downstream and fill finish solutions will be discussed to elucidate on building a successful CMC production strategy to meet patient demands and global supply. Manufacturing solutions to support early-through-late stage cell therapy clinical studies are not readily available, with a technological chasm occurring between early-phase 'academic' solutions and commercial-ready high capital unit operations. Here, practical solutions have been derived, and are in clinical GMP operations, for an off-the-shelf cell therapy portfolio to highlight development pathways for novel therapies within a small biotech company. Specifically, solutions to address batch-to-batch variability, to support patient demand and global supply, and to present a novel fill/finish scalable solution will be shown: all designed to bridge the technological chasm and provide bioprocessing throughout clinical development and beyond. Clinical success can be streamlined through value-driven early CMC decisions, with choices led by patient and clinic-led decisions. Drug development must be supported by a robust and agile bioprocess, with the solutions presented here aiming to bridge clinical phase production strategies.
- Ben Weil - Director of Manufacturing, INmune Bio
- What steps can be taken during earlier development to prepare for commercialization?
- Formulation to ensure scalability
- Process development for reproducibility
- The importance of a robust supply chain for advanced therapies
- Fortifying the supply chain, ensuring reliable stakeholders and suppliers, efficiency for production
- Effective learning around implementation of new tools
- Pierce Kent - Head of CGT Supply Chain, Roche
VectorY develops Vectorised Antibodies (VecTabs) which utilize an AAV vector to deliver the transgene to the target CNS cells where the therapeutic antibody is subsequently produced and clears the toxic variants of target proteins to improve neuronal health and halt disease progression . The presentation will be about our AAV production platform "ManuVec" which produces VecTabs from an optimized Baculovirus/insect cell platform in high yields, quality and potency in a cost effective manner
- Pranav Puri, PhD - Head Process Development, VectorY
The most studied and well-described mode of action of miRNAs is their binding to the 3ʹ UTRs of target messenger RNAs, thereby downregulating gene expression through post-transcriptional gene silencing (PTGS). However, recent research, including our own, has demonstrated that small non-coding RNAs (ncRNAs) can also bind directly to the promoter regions of genes, either activating or repressing their transcription. This process depends on the specific loci targeted within the gene promoter, which can lead to either silencing or activation of gene transcription. The mechanism involves the recruitment of protein complexes to the promoter regions, resulting in modifications of the epigenetic status, such as histone modifications, at the chromatin level.
Utilizing this mechanism for therapy presents several advantages. Firstly, targeting non-coding RNA at the gene promoter rather than mRNA in the cytoplasm requires much less miRNA to reach the target within the cell. When miRNAs target mRNAs that are continuously produced, new miRNA must be constantly delivered to counteract the newly produced RNAs. Conversely, targeting transcription via the epigenetic mechanism requires fewer miRNA copies per cell and fewer administrations, as the effect is longer-lasting. Additionally, targeting the cell’s own gene yields a more natural cellular response, as all potential splice forms of the mRNA are regulated by the same promoter-targeting miRNA.
Our lead asset, poised for clinical trials, targets the upregulation of VEGFA for the treatment of peripheral artery disease. Independently conducted in vivo trials have demonstrated the therapeutic efficacy of our RNA medicine, providing a strong foundation for its further development. Leveraging our Platform Technology Co-Development model, powered by AI-assisted cutting-edge in-house software, we are pioneering the search for regulatory small RNAs across a broad spectrum of diseases, from oncology to neuroinflammatory conditions.
- Mikko Turunen, PhD - Founder and CSO, RNatives Inc.
- Strategies, approaches, and experiences when developing a novel gene therapy
- Important factors to keep in mind:
- Pre-emptive preparation for hurdles specific to novel gene therapies
- Mitigating risk strategies during early development
- Adaptable manufacturing solutions
- Optimizing processes to prepare for larger-scale manufacturing.
- Engaging early with regulatory agencies to avoid bottlenecks.
- Pre-emptive preparation for hurdles specific to novel gene therapies
- Considerations during clinical development, including patient selection, safety monitoring etc.
- Larry Forman - CEO, CHO PLUS
- Mikko Turunen, PhD - Founder and CSO, RNatives Inc.
Cytokine Release Syndrome (CRS) is a potentially life-threatening side effect associated with many modern immunotherapies such as CAR T cell therapy and T cell engaging bispecific antibodies. Despite incidence rates of up to 95% and significant escalation of medical costs very few treatment options are available, with only tociluzumab approved for CAR T cell induced CRS within the US. No preventative methods exist despite significant physician and patient needs. A range of investigational and repurposed drugs have been evaluated but have failed to produce sufficient reductions in CRS levels to impact patient management plans. A number of MAPK inhibitors have now been shown to enhance cell therapies and offer an ideal method to attenuate hypercytokinaemia associated with CRS without impairing immunotherapy efficacy. POLB 001 is an oral p38 MAPK inhibitor in development for the prevention of CRS. It has been evaluated in a Phase 1b LPS challenge study showing potency in dramatically reducing IL-6, TNFa, IL-8 and other proinflammatory cytokines along with meaningful reductions in heart rate, temperature and C-reactive protein increases. Phase 2 trials are planned with the intent to enable broader and safer uptake of immunotherapies in the clinic.
- Jeremy Skillington - CEO, Poolbeg Pharma
The advancement of allogeneic therapies presents a promising frontier in regenerative medicine, offering the potential for scalable, off-the-shelf treatments. However, the development of these therapies faces significant challenges, including the complexity of manufacturing processes and the need for consistent product quality. This abstract outline an approach to streamline allogeneic product development through the integration of platform automation in both 2D and 3D cell culture systems.
By leveraging automated platforms, Bayer aims to industrialize the efficiency and reproducibility of allogeneic cell production. Automation technology facilitates control over the cell culture environment, ensuring consistent cell quality and yield. In 2D systems, automation supports the standardization of monolayer cell cultures, while in 3D systems, it enables the scalable production of clusters or spheroids, which more closely mimic the in vivo cell environment.
The implementation of platform automation in allogeneic product development not only accelerates the production process but also reduces the risk of human error and variability. This approach promises to lower the barriers to entry for allogeneic therapies, making these innovative treatments more accessible to patients in need.
- Jason Dowd - Global Lead Cell Therapy Platform Process, Bayer
- Leveraging ML/AI techniques from mAbs for faster C> process development
- Mastering experimental efforts and streamlining data workflows
- Achieving up to 70% reduction in physical experiments
- Showcasing multiple industry-relevant C> use cases
- Mark Duerkop - Chief Executive Officer, Novasign, Austria
AAV has emerged as a significant therapeutic modality in gene therapy. Challenges such as poor yield and variable product quality persist in the viral vector manufacturing space and we have addressed these problems using our cell engineering technology. Our cell engineering platform for improved adeno-associated virus (AAV) manufacturing addresses the critical challenges in gene therapy manufacturing, and presents an innovative modality for improving cells for production of viral vector therapeutics. Our platform, yielding cells with improved AAV production and CQAs, can significantly bolster the efficiency and cost-effectiveness of gene therapy manufacturing, and can accelerate current development timelines. We used a directed-evolution approach based on repeated cell fusions to shuffle the cell genome, and amplify chromosomes of HEK-293 host cells. Engineered clones enriched for mitochondria phenotypes were isolated, then used as transient-transfection hosts, and for creating stable packaging and producer cell lines. For generation of stable packaging and producer cell lines, we developed a novel inducible system that maximizes the capabilities of the inherent viral production machinery. Engineered HEK-293 clones grown in suspension culture exhibited up to 15-fold productivity improvement via triple transient transfection for AAV1, AAV2, AAV5, and AAV9 serotypes with capsid titers as high as 1017 viral particles/L (vp/L)—at least 10-fold higher than current industrial manufacturing processes. Selection for certain mitochondria phenotypes resulted in a 2-fold improvement in full-to-empty ratio—up to 55% full in crude supernatants. Finally, our engineered stable packaging and producer cell lines achieved capsid titers of up to 1016 vp/L. We demonstrated a multi-modal cell-engineering platform that has significantly improved yield and manufacturability for transient transfection and for stable packaging and producer cell line methods. We further propose a model regarding the role of mitochondria for enhancing capsid percent-full. Taken together, our disruptive platform technologies provide solutions for meeting current—and future—gene therapy manufacturing challenges.
- Larry Forman - CEO, CHO PLUS
- Algorithms for optimization – how can AI predict optimal conditions to maximize yield and quality?
- Predictive analytics for cell growth, differentiation, and impurity forecasts to enhance process control
- Data-driven decision making
- How data analytics can help with heterogeneity of patient cells
- Mohamed Noor, PhD - Digitalization Manager, National Institute for Bioprocessing Research and Training (NIBRT)
- Regulatory frameworks for advanced therapies across key markets (FDA, EMA, MHRA)
- Handling the unique challenges and unknowns with advanced cell therapies
- Importance of long-term monitoring compared to previous biologics
- Accelerated Pathways
- What expedited approval mechanisms are there (PRIME, RMAT etc.) impacting innovation
- Florence Salmon - VP Regulatory Affairs, HOOKIPA Pharma Inc.
- Downstream process is a key bottleneck in the manufacturing of recombinant adeno-associated viral vectors (rAAV) for gene therapy and learnings from other biologics platforms can be challenging to adapt to rAAV modality.
- Current thinking on rAAV downstream process and challenges faced during purification development.
- Viral safety considerations of rAAV downstream process.
- rAAV viral safety and virus clearance validation based on current ICHQ5(R2) guideline.
- Yu-Tsan (Richard) Liu - Sr. Scientist, UCB Pharma
Overview of the current main economic and sustainability effects on AAV & DNA manufacturing for different demand scenarios. Calibrated process models can illustrate the design areas with the biggest impact and point to the new technologies required.
- Rob Noel - Independent Consultant, 55Biomarkets