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As an academic researcher in the blood stem cell field for the last 20 years, I’ve been involved in a large number of interdisciplinary collaborations and, more recently, a series of industry partnerships. There is no doubt in my mind that cell and gene therapy is one field that requires these types of partnerships spanning all the way from discovery science across multiple disciplines, through to investment and development from industry through to delivery in health-care systems across the world. We need to make these interactions easier to initiate, develop and sustain, but this goal sometimes appears to run counter to the current rewards and recognition frameworks at academic institutions.
I began my PhD in 2003 at the Terry Fox Lab in Vancouver at a time when stem cells and gene therapy were very hot topics on the back of the first clinical trials of corrective gene therapy using patient hematopoietic stem cells (HSCs), the discovery of human embryonic stem cells, and the publication of the first whole genome in humans.
Dr. Keith Humphries and co. (including Drs. Guy Sauvageau and Jennifer Antonchuk) had produced a run of exciting scientific discoveries about how the overexpression of a gene called Hoxb4 could expand blood stem cells in vitro. Gene therapy of blood stem cells to cure a wide range of single gene disorders with virtually limitless numbers of donor cells was seemingly within our collective grasp.
As many readers will know, the early gene therapy trials had substantial complications that inevitably curbed the enthusiasm for widespread rollout of gene therapy and set the field back considerably. Similarly, blood stem cell expansion efforts that did not require genetic modification proved more complicated than initially hoped.
Fast forward 20 years and we find ourselves amidst a very different, but equally complex, landscape. With the recent explosion of cell and gene therapies at various stages of clinical trials, there is an even more urgent need to ensure that these therapies – if successful in trials – are able to be delivered at scale.
This presents regulatory and manufacturing challenges, equity of access challenges, health-care delivery challenges and financial challenges. My blog today urges us to look to academic:industry partnerships to get some of these answers and also challenges a number of current and widespread university practices that make this unnecessarily difficult to achieve.
In the case of gene therapies involving blood stem cells, academics are incredible sources of knowledge around the target cell (the blood stem cell) and the various mechanisms of delivering gene editing cargo to that cell. Blood stem cells are the archetypal tissue stem cell and a huge number of researchers have been trained in these core concepts and techniques, and now find themselves in all stages of the process including blood stem cell research, stem cell banking, vector development and modification, industry translation and health care delivery.
The current swathe of clinical trials has relied on these experts working together across disciplines, but has also required huge investment as each drug product (e.g., the cells to be infused) are highly personalized on a per patient basis and require individual quality control checks and extensive follow-up.
The latter point becomes particularly important in the context of potential risks of prematurely developing haematological malignancies since it requires decades of follow-up to truly understand the full risk, and the numbers of patients undergoing gene therapy are still relatively small, placing an asterisk by even the most successful trials to “wait and see” what happens to individual patients.
Critical to partaking in the refinement of proven therapeutic approaches (e.g., improvements that might improve gene delivery, make it faster or cheaper, reduce toxicities, etc.) is an understanding that the heavy lifting and financial investment in the core technology has already been made. It would be wise for potential partners (universities, research institutes, etc.) to bear this in mind as they envision their role in the therapies and process improvements to come. There are huge gains to be made in the delivery of gene modification tools, drug product manufacturing and safety, but we need to do a few things to make those happen:
1) We need to talk – One of the most straightforward yet difficult to accomplish tasks is to get agreements in place to share information. Whenever academics engage with industry, non-disclosure agreements (NDAs) are regularly required from at least one of the “sharing” parties. The agreements themselves are typically fairly standard, but getting people to sign these agreements can take months and usually involves a university or research institute’s contracts office. NDAs rarely ascend to the top of a list of urgent tasks; therefore, when offices are busy, these agreements often get overlooked, leading to weeks if not months of delay in even being able to speak to potential partners. Some organizations have taken to generating generic NDAs or establishing triage systems that get “easy” jobs actioned quickly. These are both positive steps that could be adopted more widely.
2) We need to share – Next, in order to improve on something, we need to be able to use the (often proprietary) tools that are involved in the original process. Here, another piece of paperwork that is all too often slow to be signed is the Material Transfer Agreement (MTA), which covers the usage of said tools. It seems to be one of the most common complaints of academics and companies that partner with academics that these agreements are far too slow to get signed, despite the value of a tool.
In my own career, the vast majority of things I have obtained MTAs for have absolutely zero money-making potential and this was very clear up front. Where there is value in a tool or reagent, we need to realistically assess which partner created that value and allow them to protect it in an MTA. In all cases though, the value of generic MTAs for specific tools/reagents is clear, especially when it means one party has already pre-accepted the terms.
3) We can all win – The first two points are relatively easy to sort out with improved processes and resourcing, but things get tricky when partners start to work on projects together. This can take a number of forms from one-off consulting to shared grant applications or PhD students, and can move all the way through to full blown contracted research. This is where I feel the biggest barriers are located and they come in an equally broad range of formats.
Generally, these barriers are around intellectual property (IP) and financial remuneration, and I think academic research institutions would do well to consider creative approaches to these. For example, if the institution would be content to have no ownership over IP, they could almost certainly charge more for the service (e.g., in the case of contracted work where an industry partner knows your lab does X and they would like to get you to do X for them).
More structurally, we also need to consider the incentives for the staff involved in these contracts and/or negotiations: If you promote people who protect university IP positions (irrespective of how valuable those positions may be) then they will protect them. Faster, more flexible, agreements that allow companies to protect their IP and/or have exclusive licences (or even ownership) of newly generated IP can be extremely attractive for industry partners and something that universities could see as a long-term investment in industry partnerships.
Many readers may think me naïve to be so blasé about IP and the potential financial rewards of a successful venture in the cell and gene therapy space. I am not, however, suggesting we give carte blanche to companies to exploit academic institutions or individual scientists. I am simply suggesting that we consider alternate ways of making the complex landscape of scientists, innovators, health care providers and investors work better for a broader set of stakeholders. There is almost aways a creative solution waiting to be developed, but if we get stuck in structures or processes that are not fit for purpose, then we all lose. After all, 100 per cent of $0 is still 0.
My blog is just one of many covering this topic as part of Signal’s seventh annual blog carnival – click here to read what other bloggers have to say.
David Kent
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