Specialist
Former senior director at Thermo Fisher Scientific Inc
Agenda
- Major developments within the C> (cell and gene therapy) space, highlighting ongoing manufacturing advancements for CDMOs (contract development and manufacturing organisations)
- Progression of newer modalities, including GMP (good manufacturing practice)-related products, dosing to modules, viral vs non-viral and addressing the autologous vs analogous question
- Comparative dynamics among operating C> players such as Thermo Fisher (NYSE: TMO), Resilience, Danaher’s Cytiva (NYSE: DHR), Lonza (VTX: VONN), Miltenyi Biotec and Catalent (NYSE: CTLT)
- Technical challenges and expertise required to manoeuvre C> products, breaking down automation and flexibility efforts
- 12-18-month outlook for the C> manufacturing industry, discussing future scalability and standardisation options
Questions
1.
What are some front-of-mind developments and approaches you would like to highlight regarding C> [cell and gene therapy] manufacturing? Do you think CDMOs [contract development and manufacturing organisations] have been particularly successful at building out a standardised foundational workflow for this sector?
2.
Recent findings from industry standard research in 2022 showed that outsourcing of C> manufacturing is expected to drop from 44% to 22% over the next five years, as products move closer to commercialisation. Would you agree with that percentage change? What are your expectations for outsourcing and partnership rates as we move forwards?
3.
Do you expect larger companies to start leveraging their internal manufacturing capabilities for gene therapies? Is that already happening? What is the status at the moment?
4.
Could you discuss the announcement of GMP [good manufacturing practice]-related methodologies? What kind of industry-wide traction has been occurring, and are CDMOs as well as other companies recognising the increased need for GMP? How quickly is that shift occurring?
5.
What is the value proposition of a closed automated system? How far is the industry from achieving a balance between closed and open automated systems? Is that a significant technical challenge? What are the trade-offs in terms of flexibility, etc?
6.
What are the trade-offs of having a closed vs open automated system? I understand it would reduce contamination and the turnaround time in that sense, but is there a potential downside or are there complexities that companies may have to overcome with this system?
7.
Can you address the age-old question of autologous vs allogeneic? What are the advantages and disadvantages of using off-the-shelf allogeneic CAR-T cells vs autologous CAR-T cells to treat cancer? Can you provide some indication as to where the industry is headed in this case?
8.
What are companies choosing between autologous and allogeneic and for what indications? Oncology is a big issue, and rare diseases and neurology are some of the biggest therapeutic focus areas at the moment. What is going where?
9.
To circle back to your comment, what are some of the reimbursement and cost issues associated with autologous at the moment?
10.
What are some of the current manufacturing challenges associated with producing allogeneic CAR-T cells at scale? You mentioned that they may reduce the manufacturing complexities, but of course, they haven’t been able to solve that riddle. How can risks such as adverse reactions associated with receiving these allogeneic cells be minimised from a manufacturing and general cost perspective?
11.
Could you draw a direct comparison between viral and non-viral vectors, given some of the safety issues that you mentioned before, including immunogenicity? How would you assess the shift towards non-viral vectors, especially with the utilisation of AAV [adeno-associated virus] vs LV [lentiviral] gene therapies? Additionally, what are the respective associated regulatory risks?
12.
What is your view on the advancement of the electroporation segment? Could you discuss your experience with the MaxCyte processor in particular vs other delivery methods, drawing out some pros and cons? Is it going to take share over time?
13.
You alluded to safety and efficacy problems, such as high toxicity, cell damage and mortality, within the entirety of the C> space. To what extent might these hinder growth? What are some of the quality measures put in place to ensure safety and efficacy of immunotherapies, going back to the point regarding regulatory concerns as well?
14.
In terms of mixing and matching, you mentioned that customers want to have the best-in-class of each component. How is that ensured across the board and how efficiently are these systems talking to each other in terms of compatibility? Are customers able to shop around and piece together parts from various companies such as Thermo and Danaher?
15.
You highlighted collaboration, so how has the mixed combination stemmed into a lot of collaboration in the space for C>s more specifically?
16.
Could you break down some of the specific products required to conduct C>s? Thermo’s products include its Rotea system for cell processing, Xenon, its optimiser media and cell culture media, which have all been big growth drivers. What utilisation purposes do they serve and what is your demand outlook for these products?
17.
How fragmented is the CDMO space operating in the C> manufacturing space, breaking down Danaher, Lonza, Miltenyi and Catalent? Which would you consider as the front- and back-runners from a development standpoint?
18.
Who are the smaller players on the cell therapy side? We don’t have to get into specific names, but which players should we be tracking over the next couple of years?
19.
You indicated Resilience was a key competitor to emphasise, due to increased investment and diversity of service offerings. Can you elaborate? Do you think it has the potential to catch up? How are you differentiating between Catalent and the larger CDMO models from Resilience’s business models?
20.
What are the attractive end markets for C>s? Most cell therapies are focused on blood cancers and solid tumours, as you mentioned. Where do the growth opportunities lie from a scientific and margin perspective? Is there huge scope for growth outside of oncology, or is that the main focus?
21.
What is the general cost of manufacturing the types of C>s we’ve discussed? We’re not looking for specifics, but keeping in mind the operation costs for scientific and facility utilisation, how significant are these cost ramifications?
22.
Is there a possible cost-reduction strategy that could be put in place on the cell therapy side to make it more accessible and affordable to patients?
23.
Is there any particular shortage of staff or lack of expertise within C>, given it’s not new, but it is still relatively newer than most advancements in the healthcare industry? How technically challenging or labour-intensive is it, and would you consider this a restricting factor for the growth of this industry?
24.
Can you highlight 2-3 key takeaways from our Interview today that might provide some colour on the short- and long-term outlook for the C> space? Do you have any concluding thoughts?
25.
Do you expect supply chain challenges to persist over subsequent quarters in the segment, given transportation delays, the overlap with the COVID-19 vaccine distribution – which is also dying down a little bit more – and competition for some of the critical supplies?
