DUBLIN – Gyroscope Therapeutics Ltd. raised £50.4 million (US$60.5 million) to further development of GT-005, its clinical-stage gene therapy for treating dry age-related macular degeneration (AMD), and to advance a second-generation of the subretinal delivery system it gained through its recent merger with Orbit Biomedical Ltd.

Gyroscope's founding investor, Syncona Ltd., of London, led the round, with £48 million of the total, which takes its total investment in Stevenage, U.K.-based Gyroscope to £82 million. Cambridge Innovation Capital is putting in the remaining £2.4 million.

Wet AMD has long been served by several biologic therapies targeting vascular endothelial growth factor, to prevent neovascularization. Despite many efforts, as yet no therapy has been approved for the more common, dry form of AMD. Although it is less severe than wet AMD, which can result in blindness, it is the precursor of that condition. Preventing or delaying progression from dry to wet AMD would, therefore, represent a significant step in the treatment of the most common form of adult blindness.

Gyroscope's approach is based on the hypothesis that chronic activation of the complement system within the eye is an important driver of the dry AMD pathology. The accumulation of drusen – yellow-colored lipid and protein deposits – has long been recognized as a hallmark of AMD. Several complement activators and regulators are known to be present within drusen and are widely thought to play a role in the disease process.

"It's pretty well established – most people in the field think it's one of the fundamental drivers of the disease," Gyroscope chairman – and Syncona's chief investment officer – Chris Hollowood told BioWorld. Although dry AMD is obviously not a monogenic disorder, there is supporting genetic evidence that implicates the complement system. "I don't think you can say it's not a genetic disorder."

GT-005 comprises an adeno-associated virus 2 (AAV2) vector encoding an endogenous anti-inflammatory, complement regulator. The company is not publicly disclosing the protein at present, although a number of unconfirmed reports, as well as the EU Clinical Trials Register, have identified it as complement factor I (CFI), a serine proteinase that cleaves and inactivates complement C4b and C3b. A key issue – regardless of the identity of the protein involved – is whether the point of intervention Gyroscope has chosen is appropriate for the patient population being investigated. "That's the clinical question we're looking at right now," Hollowood said.

Gyroscope aims to complete enrollment onto a 10-patient phase I/II trial within the next 12 months. In parallel, it is finalizing a commercial version of Philadelphia-based Orbit Biomedical's surgical delivery system, which employs a cannula to deliver the therapeutic payload to the subretinal space, eliminating the need for a vitrectomy. The latter approach, although successfully employed in the several gene therapies that target the subretinal space, is not practical, Hollowood said, for the hundreds of thousands of patients with AMD. The Orbit approach is less invasive and more scalable. "We see it as being unique. We see nothing like it on the market. It's truly enabling for what we want to do."

The present trial is not employing the Orbit device – it got underway before the merger between the two companies was completed earlier this year – but other firms have used it successfully in clinical trials. As the Orbit procedure does not involve a vitrectomy, there is no concern about any leakage of gene therapy vectors through any retinal holes. "Once the dose is in, it stays there," Hollowood said.

A number of biologic therapies targeting components of the complement cascade have previously failed to demonstrate efficacy in phase III trials in patients with geographic atrophy, or GA, the advanced stage of AMD. The complement D inhibitor lampalizumab, which Basel, Switzerland-based Roche Holding AG was developing, failed in two phase III trials. Soliris (eculizumab), the complement factor 5 (C5) inhibitor, which New Haven, Conn.-based Alexion Pharmaceuticals Inc. markets in several rare, complement-mediated conditions, failed to demonstrate efficacy in a phase II trial in GA. Crestwood, Ky.-based Apellis Pharmaceuticals Inc., is still in the game. It is enrolling patients with GA due to advanced AMD in two phase III trials of APL-2, a C3 inhibitor.

Shares in Syncona (London:SYNC) closed Tuesday at £2.43 (US$2.94), a gain of 6% on the previous close. The company is some way off its historic highs of October 2018, but at the same time, its trading performance is markedly superior to that of the crisis-ridden Woodford Patient Capital Trust plc, the Oxford-based fund that made London such a key destination for biotech investment funds. Woodford is spread more widely – and thinly – across many areas of biotech and pharma. Syncona, in contrast, is more narrowly focused on early stage firms that have the potential to make a rapid and substantial impact on rare diseases. It has a high-engagement investment model – it takes large stakes in and works closely with portfolio companies. It has been an early participant in financing the maturation of gene therapy into an industrially robust therapeutic modality. So far, at least, that strategy appears to be working.

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