AstraZeneca Taps Pieris For Inhaled Asthma Anticalins
Executive Summary
AstraZeneca is to pay $57.5m to get its hands on biotech Pieris Pharmaceuticals' Anticalin technology to bolster its early stage respiratory portfolio, with a lead product candidate already being prepared for Phase I.
AstraZeneca is making good on its ambitions to pursue novel avenues for respiratory therapies with a deal with Boston-based biotech Pieris Pharmaceuticals to develop inhaled drugs based on its Anticalin platform of engineered proteins that mimic the actions of antibodies.
Under the new collaboration, AstraZeneca will make upfront and near-term milestone payments to Pieris totalling $57.5m; the biotech's shares on NASDAQ rose by more than 42% to $3.43 on the news on 3 May. One of the deal's attractions for AstraZeneca is that it brings access to a promising new technology platform that will bolster its back-end respiratory portfolio, with the benefit of an identified lead compound already primed to enter the clinic.
Pieris has committed to advancing this lead candidate, PRS-060, which targets IL-4Rα, into Phase I this year. AstraZeneca will fund all clinical development from Phase IIa onwards and subsequent commercialisation programmes but Pieris keeps an option for co-development and co-commercialisation in the US. The two companies will also collaborate on the development of four other Anticalin products in respiratory disease whose targets have not yet been disclosed.
Pieris's platform is also being developed for use in other therapeutic areas, and this is the third deal that the firm has struck for its Anticalin-based products so far this year. It entered into a partnership with Servier in January for PRS-332 in immuno-oncology for €30m upfront; and in February it inked a partnership with Japanese firm ASKA Pharma for its anemia candidate, PRS-080.
What Is An Anticalin?
Pieris describes Anticalins as engineered lipocalins, endogenous low-molecular weight human proteins typically found in blood plasma and other body fluids that naturally bind, store and transport a wide spectrum of molecules. The defining attributes of the 12-member human lipocalin class are a four-loop variable region and a rigidly conserved beta-barrel backbone, which, together, form a pliable cup-like binding pocket.
The Anticalin platform allows rational use of different amino acids within these four loops and ligand-binding areas of the beta barrel to produce specificity and affinity for a wide spectrum of targets to create a product with the safety of an endogenous protein performing an endogenous function. The Anticalins, Pieris says, are durable, which allows flexibility of formulation and delivery; and as they bind a target as tightly as a monovalent molecule, they overcome the complications of multivalent binding approaches, when agonist receptor cross-linking is therapeutically counter-productive.
Datamonitor Healthcare analyst Ali Al-Bazergan said the latest collaboration made sense given AstraZeneca's ambitions in this therapeutic arena. "It's not a surprising deal as the company mentioned in its Q1 results call that its ambitions in respiratory go beyond its current inhaled and biologics portfolio in order to capture the expected market expansion over the next 10 years from new targets and treatment strategies."
The respiratory therapy area is a key platform in AstraZeneca’s strategy towards long-term growth and to become an industry leader in innovative inhaled and targeted therapies. The company’s strong marketed products in Symbicort (budesonide/formoterol) and Pulmicort (budesonide) have now been supplemented by the aclidinium franchise, recently acquired from Almirall. PharmaVitae expects AstraZeneca’s respiratory portfolio to grow at a CAGR of 4.2% out to 2026, adding $2.5bn in sales as key pipeline products benralizumab (which targets IL-5Rα) and tralokinumab (anti-IL13) counter the generic headwinds of Symbicort and Pulmicort.
Intersection
PRS-060 is being developed for patients with moderate-to-severe asthma who are not fully controlled with currently available drugs. Its target is a key intersection in the Th2 pathway which plays an important part in the disease in many patients. IL-4 and IL-13 are the main cytokines involved in Th2-mediated asthma, and both signal via IL-4Rα.
In hitting IL-4Rα, PRS-060 is apeing Sanofi/Regeneron whose fully human MAb against the target, dupilumab, which is the most advanced in the class at Phase III for this indication. A US regulatory filing for asthma is expected in the US in the fourth quarter (dupilumab has just received US approval as Dupixent for its lead indication, atopic dermatitis). The only other product against IL-4Rα in the clinic is Novartis's monoclonal VAK-694 which is in Phase II as a combination product with the anti-IL-13 MAb product QAX-576.
Interestingly, AstraZeneca appears to have flirted with the target before: two preclinical candidates acting on IL-4Rα – AZD-0449 and MEDI-2405 – are listed in Informa Pharma's Pharmaprojects database as having no evidence of ongoing development for several years.
Pieris and AZ note that PRS-060 has the advantage over the antibody approaches of local delivery by inhalation which may give improved ability to target the biological drivers of disease in the lung. Pieris has demonstrated proof of concept in animals as well as feasibility for pulmonary delivery with PRS-060.
Pieris has the potential to receive development-dependent milestones and eventual commercial payments for all products not exceeding $2.1bn as well as tiered royalties on the sales of any potential products commercialised by AstraZeneca.
Pieris president and CEO, Stephen Yoder, said: "Our partnership with AstraZeneca accelerates the transformation of Pieris into a fully-integrated drug development and commercial organization, comprising two main pillars in immunology: respiratory diseases and immuno-oncology, each of which is now anchored by a major alliance."