Apellis Pharmaceuticals Inc.'s $47.1 million in series D money will let the company reach "some inflection points in rare diseases and geographic atrophy [GA] in the next year or so," general counsel David Watson told BioWorld Today, though he declined to provide specifics. "We're going to leave that open for now," he said. "We don't really want to comment on runway or plans or what we think the inflection points will be."

Crestwood, Ky.-based Apellis pulled down the money by way of a preferred stock sale to advance its complement-cascade immunotherapy programs in paroxysmal nocturnal hemoglobinuria (PNH) and GA (an advanced form of dry age-related macular degeneration [AMD]), as well as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis.

The company's technology is designed to inhibit C3, the main protein in the cascade. "A couple of competitors are essentially [working] upstream of C3," Watson said, citing Basel, Switzerland-based Roche AG's phase III GA therapy lampalizumab, a monoclonal antibody fragment that functions at the level of the alternative pathway – one of three routes of complement activation that also include the classical and the mannose-binding lectin pathways. Any way of starting the complement response "will eventually get filtered through a step involving the cleavage of the C3 complement protein," he said. "The cleaving is cut off there. We don't think GA is a particularly crowded space" at the moment, he added. "We don't know everything that's in pipelines everywhere, but we do know that lampalizumab has been the marquee drug to watch."

In a research report Friday, Leerink analyst Joseph Schwartz noted that "complement inhibition remains the mainstay of late-stage therapeutic targets in dry AMD/GA," led by the Roche candidate in the late-stage research effort that involves 2,500 patients. "This is now closely followed by [Princeton, N.J.-based Ophthotech Corp.'s] recently initiated Zimura [C5 inhibitor avacincaptad pegol sodium], with a phase II, 300-patient program." Along with the phase III SPECTRI/CHROMA trials ongoing to replicate lampalizumab's efficacy observed in the phase II MAHOLA study, Roche is sponsoring a pair of epidemiological studies to understand changes in visual function during the progression of GA, which goes relatively slowly. "Ophthotech's recently initiated phase II/III trial's 18-month interim analysis in 2018 may also be able to benefit from SPECTRI/CHROMA readout, as the company plans to expand the trial size to convert it into a full phase III pivotal program after incorporating certain enrichment criteria," Schwartz wrote, adding that he remains "very conservative" about Zimura and does not include it in his model.

In PNH, Apellis' Watson said, Soliris (eculizumab) from Alexion Pharmaceuticals Inc., of New Haven, Conn., "inhibits downstream, at the level of C5." Doing so "prevents formation membrane attack complex, which is basically a combination of proteins that acts like an augur or drill and makes holes in the membranes of red blood cells and causes them to pop," he said. "By inhibiting at C3, we think also inhibit some of these inflammatory affects that are put into motion when C3 cleaves." (See BioWorld Today, March 19, 2007.)

Apellis' ophthalmology program has reached phase II trials, and in PNH, several phase I experiments are ongoing. "We think if C3 inhibition works in PNH, we'll have a really good understanding of the pathophysiology of this disease," Watson said. Research into respiratory disease also is in phase I.

Founded in 2009, Apellis has 12 employees and was preceded by Potentia Pharmaceuticals Inc., which had an eye program licensed from the University of Pennsylvania, sold in the fall of 2009 to Alcon Inc. (now in Ft. Worth, Texas, part of Basel, Switzerland-based Novartis AG). In the licensing and purchase option agreement, subsidiary Alcon Research Ltd. gained rights to the lead candidate, POT-4, a complement inhibitor in development for AMD. Terms called for an undisclosed up-front payment to Potentia, and the agreements provided for Alcon to acquire shares of Potentia if certain development milestones were achieved. Potentia also was in line for sales-based royalty payments upon commercialization. "Apellis had the non-ophthalmic rights and began to develop those after Potentia sold," Watson said. "Through some subsequent deals, Apellis has an ophthalmic program as well that seeks to further some of the work that Potentia did." (See BioWorld Today, Sept. 12, 2008.)