Apellis Building on Its Platform with APL-2 for Geographic Atrophy

Weeks after receiving Food and Drug Administration approval for its complement factor 3 (C3) inhibitor pegcetacoplan, now known as Empaveli, to treat adults who have the rare blood disorder paroxysmal nocturnal hemoglobinuria (PNH), Apellis Pharmaceuticals has seen its stock price recover and approach a five-year high.

Apellis is sticking to its plan to pursue other indications for intravitreal pegcetacoplan – its pipeline product APL-2 – namely geographic atrophy (GA) secondary to age-related macular degeneration (AMD). “It’s truly, we believe, a platform opportunity to control C3 systemically in the body of patients with a multitude of indications,” CEO Cedric Francois, MD, PhD, said.

Apellis’ stock had been trending upward since it bottomed out in March, but approached the five-year high shortly after the FDA announcement. The GA program is not an insignificant element in that rebound.

Market Opportunity
ONeil Trader at Seeking Alpha says about Apellis, “Another important shot on goal is intravitreal pegcetacoplan in geographic atrophy. Phase III results are expected in the third quarter and represent a higher risk/higher reward proposition for investors.”

DelveInsight says the GA market size is anticipated to increase by 2030 “due to increasing GA prevalence, better understanding of disease pathophysiology, increased healthcare spending and R&D, and pipeline candidates aimed at addressing the disease from its root.”

Targeting C3
APL-2 is designed to regulate excessive activation of the complement cascade. A GA information page on the Apellis website says “the dysregulation of the complement cascade, an important part of the body’s immune system, plays a pivotal role” in GA.

In an article in Retina Specialist, Oleg Alekseev, MD, PhD, and colleagues explain, “C3 is the convergence point of the three complement pathways. It’s activated by C3 convertase to become C3a, which then becomes a core subunit of C5 convertase.”1 They go on to say that being a common relay point in the complement cascade makes it an attractive therapeutic target.

Clinical Trials
Earlier this year Apellis announced 24-month results of the Phase Ib APL2-103 study. Post hoc analysis showed a 46% decrease in mean lesion growth in eight patients with bilateral GA comparing the treated eye versus untreated fellow eye at 24 months.

Patients who participated in APL2-103 will be invited to enroll in the APL2-GA-305 GALE trial, an open-label extension study designed to evaluate the long-term safety and efficacy of pegcetacoplan in patients with GA who also complete the DERBY and OAKS Phase III trial.

DERBY and OAKS are multicenter, randomized, double-masked, sham-controlled studies comparing the efficacy and safety of intravitreal pegcetacoplan with sham injections in patients with GA secondary to AMD. The primary objective is to evaluate change in the total area of GA lesions from baseline, as measured by fundus autofluorescence.

Financials
Zacks Investment Research shows Apellis came out at the end of Q1 2021 with a quarterly loss of $2.32 per share versus the Zacks Consensus Estimate of a loss of $1.69. This compares to a loss of $2.29 per share a year ago.

The site says, “This quarterly report represents an earnings surprise of -37.28%. A quarter ago, it was expected that this company would post a loss of $0.48 per share when it actually produced earnings of $0.93, delivering a surprise of 293.75%.Over the last four quarters, the company has surpassed consensus EPS estimates just once.”

But Apellis’ stock price is on the road to recovery. Its close last Friday at $57.13 is just shy of its five-year high of $57.20 reached last December.

REFERENCE
1. Alekseev O, Lad EM, Steinle N. The complement pathway in geographic atrophy explained. Retina Specialist. 2021;7(1):30-38.