ExCel Centre, London, 19-20 March, 2024


Day 1, 19th March 2024

13:20 – 13:40

Cell Therapy for Parkinson’s Disease – Seth Ettenberg

Cell Therapy – Track 3, written by Esther How

Parkinson’s disease (PD) is a neurodegenerative disorder that impacts millions of people worldwide. PD is the second most common neurodegenerative disorder after Alzheimer’s, affecting 2-3% of the population over 65. PD’s patients usually experience symptoms such as uncontrollable movements, stiffness, and balance/coordination issues. The neuropathological hallmarks of the disease include neurological loss in the brain’s substantia nigra, leading to a deficiency in dopamine.

However, there is a ray of hope! Parkinson’s disease can be debilitating, but there’s a potential new approach to treatment on the horizon. Bemdaneprocel is an investigational cell therapy under development as a treatment for PD. Unlike traditional medications, it aims to address the root cause of Parkinson’s by replacing lost dopamine-producing neurons. Derived from human embryonic stem cells, Bemdaneprocel is a type of cell therapy that utilizes pluripotent stem cells (PSCs) that originate from human embryonic stem cells. These versatile cells have the potential to develop into various cell types. In the case of Parkinson’s, Bemdaneprocel is surgically implanted into the patient’s brain. Once transplanted, these cells have the potential to regenerate neural networks that have been ravaged by Parkinson’s, potentially restoring both motor and non-motor function for patients.

Seth presented positive results from the 18-month follow-up of the Phase I trial for Bemdaneprocel. The drug candidate was found to be well-tolerated, with no serious adverse events reported. The trial also monitored patient-reported benefits using Hauser Diary, a tool that allows patients to record their Parkinson’s symptoms every half hour throughout the day. By recording their “ON” and “OFF” time, with and without troublesome dyskinesia, the diary provides valuable data for assessing the impact of interventions in advanced Parkinson’s disease. The results demonstrate that the participants in the high dose cohort experienced an increase of 2.7 hours in “Good ON” time and a mean decrease of 2.7 hours in “OFF” time after 18 months.

Seth expressed his enthusiasm for the results, calling them “truly inspiring and exciting.” The results also showed that the transplanted cells survived and were engrafted in the brain. Notably, the mean 18F-DOPA signal, which indicates dopamine production, continued to increase even after immunosuppression therapy was stopped at 12 months.

Seth also highlighted BlueRock Therapeutics’ key milestones for 2024, which include a Phase II Trial for further clinical testing of Bemdaneprocel that is expected to roll out next quarter. This ongoing trial is a significant step forward for this drug candidate. Furthermore,  BlueRock also filed an Investigational New Drug (IND) application for OpCT-001, targeting the treatment of primary photoreceptor disease. This filing represents a major advancement in BlueRock’s pipeline. Overall, BlueRock Therapeutics is a company to watch closely as they progress their promising pipeline.

13:40 – 14:00

CAR-T cell manufacturing: Leveraging innovative solution to build a closed, modular manufacturing process – Russ Jarres

Cell Therapy Manufacturing – Track 10, written by Atiyeh Razavi

CAR-T therapy, a groundbreaking innovation, has shown promising results in treating patients by using their own T cells. However, making these personalized therapies is a complex job. It is labor intensive and involves open processes that can cause difficulties in relation to regulations and consistency of outcomes.

Russ Jarres, senior manager of strategic collaborations and alliances, talked about ThermoFisher’s mission to improve patient outcomes and address outsourcing needs to make these therapies more accessible. Currently, less than 3% of patients who could benefit from CAR-T therapy have access to it, largely due to cost and manufacturing complexity. ThermoFisher aims to improve this by leveraging innovative solutions to automate end-to-end manufacturing processes.

Their approach involves a flexible and modular workflow, facilitated by process design software. These workflows are characterized by single-use components and a transparent strategy that includes protocol generation for customers at no extra cost. Key innovations include the CTS (cell therapy systems), DynaSelect for cell activation and isolation, the CTS Rotea for gentle and efficient cell processing, and the CTS Xenon Electroporation System for optimized delivery of molecules into cells. In addition, the DynaDrive single-use bioreactor enables scalable production and viral vector manufacturing. By integrating digital and physical components, they offer enhanced process control and data management, leading to more cost-effective and efficacious products.

One exciting development is their closed, 24-hour manufacturing process for CAR-T therapy. This involves everything from activating the cells to characterizing the final product, all within a day, thereby both speeding up the process and reducing the risk of contamination. ThermoFisher’s Cell Therapy Institute (CTI) team plays a crucial role in this. They work closely with partner companies to make sure that everything runs smoothly. The company’s modular instruments can work together or separately, making sure all the important steps happen seamlessly.

In conclusion, ThermoFisher’s Gibco CTS portfolio offers GMP-compliant products supported by regulatory documentation, which is essential for transitioning from discovery to clinical and commercial manufacturing. Their manufacturing innovations can assist biotech companies with therapeutic development by mitigating risks and enhancing the efficiency of their systems.

13:40 – 14:00

Cell & Gene Therapy: Long Term Follow-up (LTFU) and Future Direction – Leveraging AI, Real World Data (RWD) and Decentralized Delivery Models – Emily Merrell

Cell Therapy – Track 3, written by Esther How

The global landscape of Cell & Gene Therapy is burgeoning, with a growing number and diversification of product technologies and target indications. However, ensuring patient safety and treatment efficacy hinges on effective Long-Term Follow-up (LTFU). Conventional LTFU methods can be both time-consuming and resource-intensive. Recognizing this challenge, Emily encouraged researchers to embrace creative and individualized approaches to address potential delayed adverse events that may arise during long-term follow-up.

Artificial Intelligence (AI) and Real-World Data (RWD) offer exciting possibilities. While the quality of AI outputs is highly dependent on the quality of data (“rubbish in, rubbish out”), the potential is enormous. Emily emphasized that AI and RWD can play a crucial role in various aspects of Cell & Gene Therapy development and patient management. These include optimizing trial planning by identifying relevant patient populations, endpoints, and biomarkers, informing portfolio decision strategies, and even aiding in engineering gene therapies by predicting biological phenomena such as AAV vector behavior (e.g., FORMsightAI). Furthermore, AI can contribute to patient safety by proactively predicting potential adverse events, such as cell therapy toxicity (as seen in iBox‘s use of long-term RWD to predict kidney transplant graft loss).

Emily spoke about how ICON delivers Real World Intelligence, a comprehensive approach that leverages innovative thinking and technology solutions to generate and communicate safety, and cost-effectiveness evidence demanded by regulators, payers, and providers. This evidence package is built upon several key pillars which include decentralization of trials, master protocols for efficient evaluation, and integration of digital health technologies. ICON also utilizes RWD for both asset strategy (identifying relevant patient populations and endpoints) and site identification, ensuring diversity and inclusion in clinical trials. ICON’s Real World Intelligence also supports the development of robust efficacy claims, safety event monitoring, and the creation of sustainable payment models. Ultimately, this approach ensures scientific and statistical rigor while embracing innovation to deliver high-quality RWE. By leveraging AI and RWD alongside LTFU data, the future of Cell & Gene Therapy promises advancements in treatment efficacy, patient monitoring, and overall safety.

14:20 PM – 14:40 PM

Points to consider when choosing a CDMO – Amina Al-Mossawi

Cell Therapy Manufacturing – Track 10

Written by Atiyeh Razavi

Amina Al-Mossawi, a QP (qualified person) at Hitech Health, gave an interesting talk on selecting Contract Development and Manufacturing Organizations (CDMOs) for cell therapy manufacturing.

Amina began by explaining that CDMOs are specialized partners that help biotech companies throughout the entire lifecycle of their therapies. Having previously worked in hospitals such as St George’s and Guy’s, as well as pharmaceutical companies, she is familiar with the importance of choosing the right partners for such activities. Amina said that it is crucial for these drug companies to choose the right CDMO as their success depends on it. She also pointed out that starting a drug company is not as simple as publishing a research paper on Nature. There are many other factors to consider!

In the biotech industry, companies often rely on CDMOs for various steps in the manufacturing process, both for clinical and commercial purposes. This is particularly because there are many small biotech companies in this rapidly growing field. However, the risk of failure is still very high, and success depends on strategic partnerships with these CDMOs. These outsourced services include process development, analytical development, manufacturing and QC testing, quality batch release, and logistics and commercial supply chain. These CDMOs have the expertise and equipment that some companies may lack, making them essential collaborators.

When it comes to choosing a CDMO, there are several key factors. Firstly, the CDMO needs to understand the purpose of the therapy and the patients who will use it. This means that they must be familiar with the disease or condition being treated, how the therapy works and its mechanism of action, trial design, patient population, SAEs (serious adverse events) and any safety concerns associated with it.

 In addition, Amina stressed the importance of technical proficiency. A reputable CDMO should be capable of smooth tech transfer and scaling up in order to be able produce the therapy in large quantities while adhering to strict regulatory standards called GMP (good manufacturing practice) and GDP (good distribution practice) and ensuring the safety and efficacy of the therapy. The GDP and GMP activities are carried out under the MHRA certificate (Medicines and Healthcare products Regulatory Agency).

Financial considerations are also crucial. Amina advised companies to be prepared for unexpected costs that may arise during the manufacturing process such as custom implications due to third country shipping and Brexit. It is essential to budget wisely and plan for expenses related to logistics, such as shipping and storing the therapy, to avoid any delays in delivering the drug to patients. When it comes to supply chain there are several factors to consider such as temperature control, shelf life, x-ray of shipment, and import licences.

Furthermore, Amina warned against common dangers in CDMO selection. Clear communication is key to a successful partnership and therefore it is very important to discuss expectations openly and honestly with the CDMO. Unrealistic expectations can lead to disappointment and delays in therapy development. As she nicely put it, if the CDMO has the ‘yes, yes, yes!’ mentality, that is a red flag as companies do normally try to upsell their services. The other red flag is the ‘one size fits all’ approach, as nowadays these services should be more specifically tailored to the clients’ needs.

In summary, Amina provided a useful guide for CDMO selection. In summary, it is essential to understand the purpose of the therapy’, to ensure technical proficiency based on national level EMA (European Medicines Agency), to know the capabilities (available expertise) and flexibility (both on time and projects management), and to plan for financial considerations, location, and maintain clear communication throughout the partnership. By following these guidelines, companies can maximize their chances of success in developing and delivering life-saving therapies to patients in need.  

Day 2, 20th March 2024

11:00 – 11:20

How do we involve the patients most in need of treatment? –  Paul Gissen

Clinical Development – Track 4, written by Esther How

Professor Paul Gissen has diverse experience in conducting numerous clinical trials with various industry partners as well as academically funded trials developing novel therapies. He sheds light on the importance of recruiting and retaining the right patients for clinical trials in rare diseases.

Designing rare disease clinical trials to support orphan drug designation presents unique operational challenges. From researchers to sponsors to patients, multiple stakeholders with different interests are involved. This adds complexity to the clinical trial design. Professor Paul further emphasizes these complexities such as finding a sufficient number of participants are difficult due to the limited patient population. Scant knowledge about the disease’s pathophysiology and natural history makes trial design intricate. Furthermore, research investigators, while being experts in the specific disease, may lack experience in conducting clinical research. Trials involving children present another hurdle, as long-term follow-up beyond the age of consent may be necessary, potentially extending transition times to adult care sites. Finally, the very rarity of the disease often translates to a paucity of data, making it difficult to design effective and informative trials. These considerations highlight the need for innovative approaches to ensure successful clinical trials for rare diseases.

Recruiting the right patients for clinical trials is paramount. A key question remains: how do we find these patients? Identifying participants poses a significant challenge. Investigators often rely on databases and select sites based on their expertise in the therapeutic area. However, as Professor Paul cautioned, investigators might overestimate their enrolment potential. While clinician referrals remain a cornerstone, it’s equally important to expand recruitment efforts beyond traditional methods. Social media, when used strategically, can serve as a powerful tool that can not only help to increase awareness about clinical trials, but also generate excitement about the trials and provide ongoing support and advocacy for potential participants.

Professor Gissen´s experience highlighted several pivotal factors that contribute to the success of clinical trials, particularly when navigating the intricate landscape of rare diseases. It all begins with a strong foundation of inclusive planning, where treatment strategies and patient recruitment methods are carefully considered in advance, harnessing approaches like leveraging patient registries and forging partnerships with advocacy groups. It is also essential to assemble a collaborative team of sponsors, partners, patient groups, and other stakeholders, all of which are united by a common vision. Well-defined processes, clear communication channels, and a profound understanding of regulatory requirements help to ensure smooth trial execution. By coupling investigators with clinical research expertise and motivated patients, they become the dynamic duo driving successful enrolment and retention rates. As the trial progresses, proactive monitoring of study performance and potential risks become the compass guiding agile adjustments and strategic course corrections along the journey.

Professor Gissen´s insights highlight the importance of careful planning, collaboration, and innovative approaches to ensure successful clinical trials for rare diseases. By addressing these challenges, researchers can bring new and effective treatments to patients with these debilitating conditions.

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