Excited by early data on an investigational IL-4/IL-13 receptor antibody it in-licensed in 2014, Aslan Pharmaceuticals Pte. Ltd. has agreed to pay its source, CSL Ltd., as much as $780 million for full global rights to the asset, ASLAN-004, setting aside earlier plans to collar a global partner. Instead Aslan’s team now plans to pay CSL $30 million upon starting a phase III study of the drug itself, after first tackling a multiple ascending-dose study in patients with moderate to severe atopic dermatitis (AD).

In its original agreement with CSL, Aslan was responsible for taking the drug through to proof of concept and identifying a partner to complete phase III development and commercialization. CSL would have received between 40% and 50% of revenues, including proceeds from out-licensing agreements. The amended agreement changes the economics, lowering CSL’s royalties on potential net sales to between mid-single digits and 10%, while promising the Australian company up to $95 million in regulatory milestones and $655 million in potential sales milestones. (See BioWorld Today, May 14, 2014.)

Aslan CEO Carl Firth called the change “an important achievement in our strategy to gain greater commercial control and retain more value from our pipeline programs,” a move that follows a strategic review and restructuring the company undertook in January after its oral, reversible, small-molecule pan-HER inhibitor, varlitinib, failed to meet the endpoint in a phase II trial in patients with HER1/HER2-coexpressing advanced or metastatic gastric cancer.

Testing of varlitinib for biliary tract cancer (BTC) is ongoing, most recently as part of a new agreement with the South Korea-backed Korean Cancer Diagnosis & Treatment Enterprise. The company has also been evaluating the dihydroorotate dehydrogenase inhibitor ASLAN-003 as a potential treatment for acute myeloid leukemia (AML). Biogenetics Co. Ltd. recently acquired rights to both products for the South Korean market. Additionally, the company is working on ASLAN-005, an antibody in preclinical development targeting recepteur d’origine nantais, or RON, an immune checkpoint inhibitor.

Now, company investigators are hoping to capitalize on encouraging early stage data that has shown I.V.-dosed ASLAN-004, a fully human monoclonal antibody that targets the IL-13 receptor alpha 1 subunit and IL-4, to be safe and well-tolerated at all doses tested.

“Analysis of downstream mediators, including phosphorylation of STAT6, a critical mediator of allergic inflammation, demonstrated complete inhibition within one hour of dosing, which was then maintained for more than 29 days,” the company said.

Data from the second part of the phase I study, testing a subcutaneous formulation, will be reported shortly, the company said. The multiple ascending-dose study in moderate to severe AD patients is expected to read out in the second half of this year.

Atopic dermatitis is the most common dermatological disease, affecting more than 200 million patients worldwide, Aslan said. But that has also made it a popular target for drugmakers, with 14 products already launched globally, two in preregistration and another 12 programs in phase III, according to Cortellis. For example, sales of Regeneron Pharmaceuticals Inc.’s blockbuster, Dupixent (dupilumab), remain strong while Dermira Inc.’s anti-IL-13 candidate, lebrikizumab, in AD recently drew significant investor attention with potentially competitive data. (See BioWorld, March 19, 2019.)

In addition to AD, Firth said Aslan’s team looks forward to determining ASLAN-004’s potential in other inflammatory indications.

As of March 31, Aslan had cash and equivalents of about $21.6 million. U.S.-listed company shares (NASDAQ:ASLN) fell 9% on Friday to $2.91 as the company announced plans to raise up to $15 million to fund the expansion cohorts for ASLAN-003 in AML and the multiple ascending-dose study for ASLAN-004 in AD.

Representatives of Aslan did not respond to a request for further information.