Bringing next-generation gene therapy to the clinic

Giulia Agliardi Written by Giulia Agliardi
Published on 08 September 2017
7 min. read

An interview with Dr Andrea Spezzi, Chief Medical Officer of Orchard Therapeutics

Orchard Therapeutics is a biotechnology company funded in November 2015 as part of a partnership with leading research centres, including University College London (UCL) and Great Ormond Street Hospital (GOSH); University California Los Angeles (UCLA) and Boston Children Hospital (BCH), Harvard.

Orchard’s mission is to translate gene therapy to treat life-threatening diseases such as Adenosine Deaminase Severe Combined Immunodeficiency (ADA-SCID) and Mucopolysaccharidosis Type IIIA (MPS-IIIA). The company takes advantage of the latest technology to isolate the patients’ stem cells, genetically correct them outside the body to replace the missing or faulty gene and then transplant them back into the patients. To find out more about Orchard Therapeutics visit:

We discussed with Dr Andrea Spezzi, Orchard’s Chief Medical Officer (CMO) about the challenges of translating pre-clinical research from bench to bedside.


Orchard therapeutics has partnered with many leading gene therapy centres both in Europe (including UCL and GOSH) and the USA (UCLA/BCH). This means there is a strong collaboration with academia. Can you tell us more about how the company was created?

Orchard Therapeutics was created around several research institutions, including University College London (UCL), University of California Los Angeles (UCLA) and Boston Children’s Hospital. These institutions have a strong expertise in the field of ex vivo-gene therapy and already had extensive collaborations. When trying to translate their research into clinical trials they realised how challenging it can be to get approval through regulatory agencies such as the Food and Drug Agency (FDA) and the European Medicine Agency (EMA).

From this initial challenge, the idea arose of funding a company with the specific role of accelerating the translation to clinical development, approval by regulatory agencies and making the product available to patients worldwide.

Bobby Gaspar (Professor of Paediatrics and Immunology at UCL Institute of Child Health and Chief Scientific Officer at Orchard) got in contact with F-Prime Capital (a global healthcare venture capital firm) and – through UCL Business – contacted the other institutions and coordinated the foundation of Orchard.


Can you tell us more about the company structure? Is the research performed within the partner academic institutions? How does the collaboration work? 

At the moment, the academic institutions are involved in the generation of proof of concept and pre-clinical validation. Orchard provides support and guidance to a set of indications for the translation to a clinical setting. Since the company is still small, it relies on a Contract Research Organisation (CRO) and contract manufacturers for the production of “Good Laboratory Practice” (GLP) and “Good Manufacturing Practice” (GMP)-scale products. These are high-quality products which are required for the translation of ex-vivo gene therapy to patients. The idea is that as the company grows, it will have its own in-house manufacturing facilities.   


Funding a company focussed on gene-therapy for rare diseases holds many challenges. Gene therapy is a highly personalised and expensive therapy with a much smaller market compared to major fields such as oncology or cardiovascular diseases, for example. How is Orchard planning to overcome this challenge?

Gene therapy is a relatively new technology, with only one product in the market available in one single country, and we are still working out how to implement ex vivo gene therapy in the real world, but we do have a solid plan at Orchard. 

Orchard’s pipeline includes indications where patients currently undergo bone marrow transplantation and our experts are used to ship  cells and materials around the world. Ex-vivo gene therapy will take advantage of the same infrastructures already in place, so we will not need to set up new platforms. As per the size of our indications, the current plan is to work on several different indications: at the moment, we are focussing on our most advanced leading program, ADA-SCID, we will learn from our experience with this small and manageable disease and we will translate it to other indications. Currently, our pipeline focusses on mono-allelic disease such as ADA-SCID and metabolic diseases such as Mucopolysaccharidosis Type IIIA (MPS IIIA), but as our expertise grows we will expand to other diseases too. We hope to become a model for other companies to follow.


What do you think is the hardest step to translate academic research into a commercially available product?

I think the main gap is the ability of many academic researchers to think not only about science but also business. What makes a good case for a good scientific paper does not necessarily make a good case for business. Sometimes, a great scientific idea is not enough to make a good marketed product.

To fill this gap, it would be very useful if scientists could learn to organise a business case beforehand, at the start of a project. A possible solution would be that institutions should appoint dedicated people to work on business development and project management. These roles could closely work with researchers to have a more efficient project/product development. I also think it is important for key institutions to work more closely with big pharma companies and biotech start-ups.  

On the other hand, scientists should be trained since the early stages of their careers to think more from a business point of view. This could be achieved by attending training courses or spending some time in secondments at pharmaceutical companies to gain insights into product development strategies.

A second issue is that academic researchers are often “naïve” when it comes to the requirements that regulatory agencies ask to approve new treatments. My suggestion to the new generation of researchers is to start from the beginning to learn the requirements in terms of laboratory practice (GLP), manufacturing practice (GMP) and clinical practice (GCP). For example, EMA runs lots of training courses which would be very helpful for academics, as being aware of these standards would speed up the process of translating research to the market.  


What is your role within Orchard as Chief Medical Officer?

As CMO, I am responsible for the clinical development team, all the clinical platforms that are in our pipeline and clinical operations, including safety and pharmacovigilance. I am the final person responsible for everything that goes to regulatory agencies, both in terms of efficacy and safety.

Moreover, I am involved in all business development activities, therefore I am in charge of exploring new diseases to target and to expand the company’s pipeline. I also represent the company at external forums, and when it comes to fundraising and when looking for new investors to keep the business going.


You worked for several years in big pharma companies such as GSK and Takeda. What do you reckon are the main differences with a small biotech company?

Companies like GSK and Takeda have lots of resources and expertise. In such a company, it is possible to gain experience through several training opportunities which would not be possible in a small biotech. On the other hand, since they are so big, it is more difficult to work on niche markets. From this perspective, a small biotech is more dynamic, and collaboration with academia is easier and more flexible.

Moreover, as the structure is “flat”, as opposed to big companies which are more hierarchical, you can get exposed to many aspects of management and business development from the start, while in big companies this happens only at a senior level.


You worked for several years as a paediatrician before moving to a company. What drew you to move to industry?

For me it was frustrating to see patients which could not access the best treatments available, only because they were not close enough to key hospitals. By moving to industry, I felt like my skills could impact a much bigger population and help patients all around the world to benefit from the breakthrough scientific ideas that we translate into products that could change their lives.


What would be your suggestion to young researchers who want to move to industry?

My first piece of advice would be to understand the differences between academia and industry. In academia, budgeting, project management and timelines are often underestimated. Understanding these requirements is pivotal when working in industry. Understanding requirements of regulatory agencies (FDA and EMA) is also equally important.


What would be your advice for future entrepreneurs and leaders?

To be an entrepreneur requires many skills, just having an idea – even a good one – is not enough. First of all, a leader has to be prepared and understand project management and regulations. But being a leader is not only this. A good leader must be able to navigate different disciplines; a combination of various skills is required: retaining talent, inspiring people and helping them to work on their strengths and manage their weaknesses individually and as a team, absorbing and buffering insecurities within your team, being resilient and driving the team to achieve set goals. Moreover, a leader has to adapt to the different stages of the company, as it grows bigger, changes over time and becomes more complex. Adaptability, focus, resilience, team work and energy are key to success.    

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