Nightstar Therapeutics Ltd., a retinal gene therapy company spun out of the University of Oxford, UK, has filed a Form-1 with the United States SEC to raise up to $86.25M in an initial public offering on the NASDAQ Global Market. The company will adopt the symbol “NITE”. In their registration statement to float the company, Nightstar describe themselves as “a leading clinical-stage gene therapy company focused on developing and commercializing novel one-time treatments for patients suffering from rare inherited retinal diseases that would otherwise progress to blindness.” The company proposes to develop a pipeline of proprietary product candidates designed to modify or halt the progression of inherited retinal diseases for which there are no current treatments. Nightstar’s current lead product candidate, “NSR-REP1”, targeting choroideremia, is scheduled to enter phase III clinical development in the first half of FY2018 and, according to the company, “represents the most clinically advanced product candidate for this indication worldwide.” The company is additionally developing products for X-linked retinitis pigmentosa and Best vitelliform macular dystrophy. The proposed IPO represents a major achievement for the UK company and its Oxford founders, in addition to setting an encouraging environment for the potential launch of a viable gene therapy treatment for a number of retinal disorders.
In respect of NSR-REP1, the company had previously reported data from 32 participants recruited to four open-label clinical trials, showing that over 90% of patients maintained their visual acuity over a one-year follow-up period. Previous clinical studies conducted by an Oxford University team, led by Prof. Robert MacLaren, delivered the prospective therapy surgically by subfoveal injection, comprising 0.6–1.0 X 10^10 AAV.REP1 genome particles in a fixed volume of 0.1mL. Assessment of therapeutic benefit involved a variety of functional tests including best-corrected visual acuity (BCVA), micro-perimetry and retinal sensitivity assays to compare pre- and post-surgical values (6 months after surgery). The results showed that patients with advanced disease and low baseline BCVA gained 21 letters and 11 letters (> two and four lines of vision) while near normal BCVA at baseline recovered to within one to three letters. The mean gain in visual acuity overall was reported to be 3.8 letters (SE 4.1). Measurements of dark-adapted micro-perimetry indicated that maximal sensitivity increased in treated eyes from 23.0 dB (SE 1.1) at baseline to 25.3 dB (1.3) after treatment (increase 2.3 dB [95% CI 0.8–3.8]). Over a 6-month period of assessment all patients tested showed an increase in retinal sensitivity in the treated eyes (mean 1.7 [SE 1.0]), which additionally appeared to correlate with AAV dose administered per millimetre of surviving retina (r=0.82, p=0.04). In comparison, in control eyes, the Oxford group reported small non-significant reductions (p>0.05) in both maximal sensitivity (–0.8 dB [1.5]) and mean sensitivity (–1.6 dB [0.9]).
Nightstar was originally founded to commercialise the choroideremia gene therapy treatment developed by Professor MacLaren at Oxford’s Nuffield Laboratory of Ophthalmology. In Spring 2014, Syncona LLP, an independent subsidiary of the Wellcome Trust, the University of Oxford, and its technology transfer arm, Isis Innovations, announced a £12 million investment in the then named “NightstaRx Ltd”. Since then, the company has gone through several fund raisings as its product candidates have progressed through key development milestones. Most recently, in June 2017, the company completed a $45M private placement with current and new investors.