Keeping an eye on DARPins

Molecular Partners, Allergan announce a pair of ophthalmology-focused agreements based on Molecular Partners' DARPin platform

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IRVINE, Calif.—A pharmaceutical alliance got a boost todayas Allergan, Inc. and Molecular Partners AG announced that they have enteredinto two separate agreements for the discovery, development andcommercialization of proprietary therapeutic DARPin products for therapies forserious ophthalmic diseases. The agreements are the latest expansion of thecompanies' relationship. Molecular Partners will receive a total of $62.5million in upfront payments between the two agreements, with the possibility ofreceiving additional success-based payments, including a potential total of$1.4 billion in aggregate development, regulatory and sales milestones as wellas tiered royalties in the low double digits based on future product sales.
"With Allergan we have found the ideal partner to generate astrong pipeline of DARPin-based drug candidates with the goal to treat retinaland other severe ocular diseases," Christian Zahnd, Ph.D., CEO of MolecularPartners, said in a press release. "This significant expansion of our agreementtogether with the fast progress in the ongoing phase IIb development ofAGN-150998 / MP0112 is a great validation of the DARPin approach."
MP0260 is a small therapeutic protein with dual activitythat inhibits all relevant forms of vascular endothelial growth factor A(VEGF-A) and platelet-derived growth factor B (PDGF-B). Preclinical models haveshown the compound to demonstrate high efficacy and long intravitrealpharmacokinetics, and it is currently being investigated as a treatment for wetAMD.
The first deal consists of an exclusive license agreementfor designing, developing and commercializing a dual anti-VEGF-A/PDGF-B DARPin(MP0260) and related backups, indicated for the treatment of exudativeage-related macular degeneration (AMD) and related conditions. Per the terms ofthe agreement, the companies will collaborate on development of MP0260 throughthe human proof-of-concept stage, after which Molecular Partners has the optionto co-fund Allergan's subsequent development costs in exchange for a sizeableincrease in its share of royalties.
The second agreement establishes an exclusive discoveryalliance in which Molecular Partners and Allergan will collaborate on thedesign and development of DARPins against selected targets implicated inseveral serious eye diseases. Allergan has the right to exercise three optionsto exclusively license ophthalmology compounds from the collaboration duringthe research phase. For each option that is executed, Molecular Partners iseligible for an option exercise fee, and Allergan will be take over soleresponsibility for all downstream development, manufacturing andcommercialization.
"This is an important step forward in our strategy to buildon strong partnerships with the leaders in a therapeutic area" Patrick Amstutz,Ph.D., chief business officer of Molecular Partners, said in a statement."DARPins are potent biologics which may address significant unmet medical needsin large patient populations in various disease areas."
Molecular Partners' DARPins are a new class of protein drugsthat offer increased potency and target specificity. The proteins are capableof being selected to bind to any target molecule with significant specificity,offering potential in agonistic, antagonistic or inhibitory drug compounds.DARPin candidates can also be engineered to include additional enhancement ofcertain pharmacokinetic properties, adaptation to carry different effectorfunctions or multiple binding specificities.
"As a leader in ophthalmology, Allergan is committed todeveloping new treatments for serious eye diseases like AMD," said Scott M.Whitcup, M.D., executive vice president of research and development and chiefscientific officer of Allergan, in a statement. "We look forward to furtherdeveloping a novel therapy that blocks both VEGF and PDGF, as a potential wayto improve vision in patients with wet AMD."

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