DUBLIN – Affibody AB is getting $10 million up front and up to $215.5 million in regulatory and sales milestones from a licensing deal with Inmagene Biopharmaceuticals Co. Ltd., in which the latter firm gains commercial rights to its interleukin-17 inhibitor ABY-035 in China, Hong Kong, Taiwan, Macau and South Korea.
Solna, Sweden-based Affibody retains global rights to the drug outside of those territories and will receive royalties on sales booked by Shanghai-based Inmagene. The two firms will share certain global development costs, and Inmagene will be entitled to receive limited milestone payments and royalties from global sales. “It’s a Chinese deal, and it’s a bit more than a Chinese deal,” Affibody CEO David Bejker told BioWorld. “It’s a global co-development deal with Chinese commercialization terms attached.” Affibody is free to license the drug in other parts of the world.
ABY-035 is currently undergoing a phase II trial in 100 psoriasis patients. Data are due “within a month or so,” Bejker said. The company’s timing was fortuitous. The last patient visit was completed in the early stages of the COVID-19 pandemic. The primary endpoint of the one-year study, which was conducted in Germany, is the percentage of patients achieving a minimum 90% improvement in the Psoriasis Area and Severity Index (PASI) – meaning a minimum 90% clearance of psoriasis lesions – after 12 weeks. Secondary endpoints include the same PASI response at 24 weeks and 52 weeks, as well as other efficacy and safety endpoints.
The two companies then plan to evaluate which other autoimmune indications would be appropriate for ABY-035. Affibody’s guiding strategy is to look for “places and spaces where the technology has a competitive edge.” Its Affibody platform, which is derived from the immunoglobulin-binding domain of Staphylococcus aureus protein A, can generate small antibody mimetics of 6.5 kilodalton molecular weight. (Antibodies, in contrast weigh in at about 150KDa).
Three monoclonal antibodies targeting IL-17 signaling have already gained approval in psoriasis and other autoimmune indications. Cosentyx (secukinumab) and Taltz (ixekizumab), marketed by Basel, Switzerland-based Novartis AG and Indianapolis-based Eli Lilly and Co., respectively, both target IL-17 directly. Siliq (brodalumab), marketed in the U.S. by Laval, Canada-based Bausch Health Cos. Inc. (formerly Valeant Pharmaceuticals) and in Europe (as Kyntheum) by Ballerup, Denmark-based Leo Pharma A/S, targets the IL-17 receptor (IL-17R) and carries a boxed warning about suicidal behavior and ideation. Cosentyx is now the best-selling drug at Novartis, with first-quarter sales this year of $930 million. Lilly posted $443.5 million in Taltz sales for the same period.
ABY-035 has best-in-class potential, Bejker said, because of its design. It is a bivalent heterodimer, comprising two linked affibodies that bind two different IL-17 epitopes. That construct is coupled to a third component, Albumod, Affibody’s small albumin-binding domain, which extends the molecule’s half-life. The entire molecule has a molecular weight of 18KDa. As well as providing for ease of manufacturing, the company has generated preclinical evidence to suggest it may have better uptake by the skin and joints than a full-sized antibody. The presence of bacterial amino acid sequences in the drug has not created any safety or tolerability issues thus far – and some patients have been on the drug for two years, while many others have been on it for 18 months, Bejker said.
ABY-035 is being positioned as an autoimmune disease drug, but a recent commentary from Omar Pacha and colleagues at MD Anderson Cancer Center in Houston proposed that IL-17 inhibition should be considered as a treatment to prevent the development of acute respiratory disease syndrome (ARDS), a life-threatening complication of COVID-19 infection that arises from an overwhelming immune cascade that causes acute lung injury. The rationale for that strategy stems from its role as a master regulator of inflammation, upstream from pro-inflammatory cytokines such as IL-1beta, IL-6, tumor necrosis factor alpha (TNF-alpha) and interferon gamma. Their proposal, titled “COVID-19: a case for inhibiting IL-17?,” appeared in the May 1, 2020, issue of Nature Reviews Immunology.
COVID-19 is not a current priority for Affibody, Bejker said, but at the same time the company is investigating the feasibility of an inhaled formulation of ABY-035, as part of its ongoing platform development efforts. “We’re running animal work on that this summer,” Bejker said.
The current deal is a fillip for the Affibody platform, following a setback in February, when Boston-based Alexion Pharmaceuticals Inc. decided to terminate its interest in ABY-039 after a phase I trial. The molecule, which targets the neonatal Fc receptor (FcRn), was the subject of a license deal in IgG-mediated diseases last year involving $25 million up front and up to $625 million in potential milestones. “We’re in a fact-finding mode with them,” Bejker said.