SUN-293 - Production and Characterization of OPK8801001, a Novel Long Acting hGH Antagonist for the Treatment of Acromegaly

Background: OPKO Biologics develops biobetter long acting therapeutic proteins, including Ngenla™, an approved long acting human growth hormone (hGH). OPK8801001 is being developed as a novel long acting hGH antagonist for the treatment of acromegaly, enabled by proprietary stabilizer proteins that reversibly associate with the active drug via noncovalent interactions. This approach prolongs pharmacological activity and enables once weekly dosing. The global market for acromegaly therapies is estimated at USD 2.5–3.0 billion annually, of which approximately USD 300 million is attributable to Somavert.

Aims: To characterize OPK8801001 drug substance and product with respect to protein quality, formulation attributes, and pharmacological activity.

Methods: Orthogonal analytical methods were used to assess identity, purity, structural integrity, and formulation properties. In vitro activity was evaluated by competitive binding to the human growth hormone receptor (GHR), with affinity quantified by surface plasmon resonance. In vivo pharmacokinetics and pharmacodynamics were assessed following subcutaneous dosing in rats, cynomolgus monkeys, and Göttingen minipigs, using serum IGF 1 suppression as the primary biomarker.

Results: OPK8801001 showed consistent physicochemical and functional quality across batches and low viscosity compatible with 31 gauge needle delivery. In vitro, OPK8801001 demonstrated potent GHR antagonism (IC₅₀ ≈ 6.5 nM), approximately 20 fold greater than Somavert, and very high affinity GHR binding (mean Kᴅ ≈ 37 pM) driven by rapid association and slow dissociation. In vivo, OPK8801001 produced robust, dose dependent, and sustained IGF 1 suppression across species. Maximal reductions reached ~55–65% in rats (half life 15–20 h), 42–75% in cynomolgus monkeys (half life 37–44 h; suppression ~6–8 days), and up to ~75% in minipigs with effects lasting up to 9 days.

Conclusion: OPK8801001 is a highly potent long acting hGH antagonist with favorable pharmaceutical properties and sustained efficacy across nonclinical species, supporting its potential as a once weekly alternative to daily acromegaly therapy with an estimated weekly dose of 30-80 mg, anticipated to normalize the IGF-1 levels

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