Taking the fight to Choroideremia: The Nightstar Story

Nightstar is a biopharmaceutical company with substantial funding provided by Syncona Partners, the healthcare investment company of the Wellcome Trust. The Company has been established to initially focus on developing and registering an AAV.REP1 retinal gene therapy for Choroideremia in the US and Europe. Choroideremia is a rare inherited cause of blindness and the development program builds on the successful Phase I/II study published in the Lancet Medical Journal in January 2014.

Biotech and Money was fortunate to find time with Melanie Lee, its CEO, to discuss the history and progress of the company to date, its aims and future milestones.

B&M: A good place to start is understanding your story. So if you could tell us briefly your elevator pitch.

Melanie Lee: Nightstar is the first therapeutic spin out financed by Syncona. The licensed technology is from Oxford University, from the pioneering work of Professor Robert McLaren, who is both a significantly experienced ophthalmic surgeon as well as someone who did a PhD in molecular genetics and understands gene therapy. Professor MacLaren put the 2 together and has chosen to treat genetically inherited disorders of the eye with a gene therapy methodology. Professor MacLaren’s chosen indication is Choroideremia; an X-linked disorder affecting mainly males.

This is a disease, which affects 1 in 50,000 human beings fairly uniformly around the world, although you do get clusters of occurrences in populations which tend to be more isolated and where there are more siblings or close relative marriages, as with every genetically inherited disease.

Nightstar has been set up to initially focus on the pioneering work in Choroideremia using the licenced technology; an adeno associated virus technology (AAV), where the virus particles are injected into the eye, directly under the retina, onto the layer of cells that require them, (retinal pigment epithelium and photoreceptor cells). The virus carries with it a gene, REP1, which is known to be defective in these Choroideremia patients.

Nightstar intends to take this right through to approval in EU and US. The knowledge we will have learnt will enable us to broaden our pipeline in the ophthalmology space.

B&M: Is it the nature of the fact it is a gene therapy treatment that makes what you’re doing unique or purely that no other company is doing exactly what Nightstar is doing?

Melanie Lee: The disease is classified as an orphan indication, but it manifests quite predictably and severely over a period of 40+ years, leading to inevitable blindness. There is no treatment at the moment because these people who have Choroideremia have a defective gene and due to the activity of the protein from the REP1 gene the only concepts that might lead to effective treatment of Choroderemia patients appears to be gene or cell therapy.

So to answer your question specifically, it’s one of several genetically inherited diseases that could be treated by gene therapy. A US study currently treats an extremely rare and severe eye condition, Lebers Congenital Amaurosis, using AAV gene therapy, which has shown extraordinary results restoring sight to children which has been shown to be long lasting (>9years to date). Nightstar is pioneering gene therapy treatment in Choroideremia. Other opportunities to treat Choroideremia using cell therapy or retinal transplant may be developed, but these technologies are some way behind being clinically available. So we’re in front in that respect.

B&M: Am I right in thinking that you received some initial favourable results back in a study in January?

Melanie Lee: Yes. When we licenced the technology from Oxford University and Professor McLaren, we did so on the back of a phase I/II study that Professor McLaren had undertaken. That study, which was approved for clinical entry by the MHRA some time ago, entailed an injection into one eye of 6 patients with Choroideremia at one particular dose followed by a further 6 patients at a higher dose. Data from the first 6 patients has been followed for over two years now and shows good safety and efficacy.

Importantly for most patients there was an improvement in vision in the treated eye. In particular, in 2 relatively late-stage patients there was a significant improvement in their visual acuity and this is something that had never been seen before. Other parameters such as clearer night vision and a better appreciation of colours were experienced.

B&M: The ultimate goal is to take this all the way through to the clinic for approval, but beyond the results you mention, the phase I/II through Professor McLaren, what is next on the agenda in terms of interim goals?

Melanie Lee: Previously to licensing the technology to Nightstar, Professor McLaren and his team had been planning to conduct investigator led studies and we intend to facilitate these studies.

Nightstar has the existing vector stock and is working to make this available to the investigators for their own studies. This will happen towards the end of this year and during the beginning of next. Nightstar’s strategy is to ensure that early on in our strategy we have a reliable GMP supply of this vector stock that meets the required regulatory standards. So that’s been our main focus this year and will continue to be so.

So our strategy entails securing a manufacturing route and supply, analysing further clinical results across the experienced network of investigators, and then conducting Nightstar’s own pivotal study.

B&M: In terms of the challenges, you mentioned you’ve been working on the regulatory approval side and obviously tying that in with the additional clinical data and original investigator data. Are there other things standing between you and that milestone?

Melanie Lee: My job as CEO of Nightstar is to transition the work from an academic setting to an industrial setting in order to be able to meet the requirements of the regulators. These days the regulators are extremely supportive of the modality of gene therapy. They’re understanding specifically to appreciate the features of the particular disease you’re working on; so in our case Choroideremia and understanding how to describe it, including knowing what happens to the patients, what are important end points for the patients and what can we expect from the therapy.

So we have to transition and translate what the clinicians know and the patient wants into what is suitable as regulatory material and a process to gain approval. All I can say is that the initial data in the clinic is what attracted Syncona to fund the company and what attracted me to come to establish the company and set the business plan and strategy. So it’s very encouraging data. There’s a real need for a breakthrough treatment for Choroideremia patients.

To read the remaining half of this executive interview, you can access the full transcript here for free.

  • What beyond transition has been your main responsibilities?
  • What is it that Syncona Partners are bringing to the table beyond obviously the financial support?
  • What are some of the key learning facets that you’ve brought from your previous role that you’re also applying at Nightstar?
  • Can you focus on one key piece of advice or element from what you’ve just mentioned
  • What is the single biggest thing keeping you awake at night at the moment?
  • Do you think the timing was good for Nightstar in terms of it becoming a commercial reality?
  • What does success look like for you personally for the CEO for Nightstar?


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