Alexion Pharmaceuticals today announced a pair of collaborations totaling potentially more than $1.3 billion—one partnership aimed to co-developing an autoimmune disease treatment, and another aimed at expanding Alexion’s pipeline into peptide therapies.

Alexion agreed to co-develop Affibody’s Phase I bivalent antibody-mimetic ABY-039 for rare Immunoglobulin G (IgG)-mediated autoimmune diseases, the companies said today, through a collaboration that could potentially generate $650 million or more for Affibody.

ABY-039 is designed to target the neonatal Fc receptor (FcRn), combining Affibody’s protein therapeutics platform (Affibody® molecules) and Albumod™ technology to achieve a long half-life. That half-life, along with its small size, provides the potential for less frequent, convenient, at-home, subcutaneous administration, according to the companies.

Affibody molecules are a class of small optimized proteins with high affinity based on a non-immunoglobulin three-helix bundle domain scaffold. Due to their small size, the molecules are capable of rapid tissue penetration and more efficient delivery of higher-molar doses for the same mass compared with larger proteins. The molecules are also robust enough to offer the potential of alternative therapeutic administration routes.

Affibody’s Albumod platform uses a small optimized protein with an albumin-binding domain (5 kDa) with high affinity to albumin (sub pM), with the aim of providing a half-life extension and a wider distribution profile than antibodies to Affibody molecules and other therapeutic proteins.

ABY-039 is being evaluated in a first-in-human Phase I trial (NCT03502954) in healthy volunteers. The adaptive, double-blind, placebo-controlled study is designed to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of ABY-039, with data from the clinical study intended to aid in dose selection for future studies.

Alexion and Affibody added that they are assessing potential indications for future development of ABY-039.

“We believe there is significant opportunity to transform patient care with FcRn-targeted therapies and are thrilled to add a second clinical-stage anti-FcRn medicine to our pipeline with this collaboration,” John Orloff, MD, executive vice president and head of R&D at Alexion, said in a statement. “While clinical development is still early, we are excited by ABY-039’s potential to be an optimal subcutaneous therapy across a number of IgG-mediated diseases, providing patients with the possibility of a convenient self-administered treatment option.”

Neonatal FcRn rescues IgGs from lysosomal degradation by binding them to endosomes and returning them to the bloodstream, helping to prolong the half-life of IgG. This activity contributes to a normal immune response in healthy people. However, in many autoimmune conditions, FcRn prevents lysosomal degradation of pathogenic IgGs associated with driving the disease. Blocking the FcRn–IgG interaction has the potential to drive degradation of IgG within cells and rapidly reduce circulating pathogenic IgG, the companies reason.

Alexion has agreed to pay Affibody $25 million upfront, up to $625 million tied to achieving development- and sales-based milestones, and tiered low-double-digit royalty payments.

Alexion will lead joint clinical development of ABY-039 and commercialization activities. Affibody has the option to co-promote ABY-039 in the United States and will lead clinical development for an undisclosed indication.

The companies said they expect to close their transaction in the second quarter of this year, subject to clearance under the Hart-Scott Rodino Antitrust Improvements Act.

Peptide Collaboration

Separately, Alexion also inked a collaboration agreement with Zealand Pharma to discover and develop novel peptide therapies for complement-mediated diseases, in a deal that could generate a potential $695 million or more for the Danish biotech.

The agreement gives Alexion exclusive worldwide licenses, as well as development and commercial rights, for up to four targets within the complement pathway.

According to Alexion, peptide therapies offer advantages that include high selectivity and potency, the ability to dose at low volumes, and the potential to treat a broad range of complement-mediated diseases.

“We are excited by the potential to explore different targets in the complement pathway and look forward to building on Alexion’s more than 20 years of complement expertise with the development of next-generation peptide therapies in collaboration with Zealand Pharma, which may provide the opportunity to treat many additional diseases,” Orloff stated.

That expertise includes development by Alexion of the first two complement inhibitors, Soliris® (eculizumab) and Ultomiris™ (ravulizumab-cwvz). Soliris carries indications in paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and generalized Myasthenia Gravis (gMG) in adults who are anti-acetylcholine receptor (AchR) antibody positive. Ultomiris is indicated for adults with PNH.

Alexion agreed to pay Zealand $25 million upfront for the first target, and a concurrent $15 million equity investment in Zealand Pharma at a premium to the market price as of the collaboration effective date.

For the lead target, Alexion has agreed to also pay Zealand development-related milestones of up to $115 million, as well as up to $495 million in sales-related milestones and the potential for high single- to low-double-digit royalty payments.

Alexion can select each of the three subsequent targets for an option fee of $15 million, with the potential for additional unspecified development-milestone, and sales-milestones and royalty payments at a reduced price to the lead target, the companies said.

Zealand will lead the joint discovery and research efforts through the preclinical stage, with Alexion leading development efforts beginning with IND filing and Phase I studies. The agreement provides Alexion with exclusive worldwide licenses and commercial rights to the peptide therapies developed in the collaboration.

“Alexion’s demonstrated expertise in treating rare and complement-mediated diseases makes this the ideal collaboration to advance Zealand’s complement-focused peptide programs,” added Adam Steensberg, interim CEO and chief medical and development officer at Zealand. “Collaborating with Alexion is further evidence of the strength of our peptide discovery platform, which has delivered both approved novel peptide-based therapeutics and a deep late-stage pipeline.”

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