Apollo Therapeutics Announces Science Translational Medicine Publication Supporting APL-9796 as a Potential Disease-Modifying Approach for Pulmonary Hypertension

• Published data validates ZIP12-mediated zinc signaling as a novel driver of pulmonary vascular remodeling and supports a differentiated therapeutic approach targeting underlying disease biology 
• Phase 1 trial in healthy adults showed subcutaneous APL-9796 was well tolerated and demonstrated dose-dependent pharmacokinetics
• APL-9796 is currently being evaluated in ViTAL-PH, a Phase 2 trial in adults with pulmonary hypertension (NCT06846554)
  
  

BOSTON and CAMBRIDGE, United Kingdom, Oct. 22, 2026 (GLOBE NEWSWIRE) -- Apollo Therapeutics (“Apollo”), a biopharmaceutical company focused on translating breakthrough science from top global universities into differentiated medicines, today reported the publication of a manuscript in Science Translational Medicine describing the discovery and development of APL-9796, Apollo’s investigational monoclonal antibody ZIP12 antagonist as a potential disease-modifying approach for pulmonary hypertension (PH). This work was conducted through a long-standing collaboration between Apollo Therapeutics and researchers at Imperial College London.

The publication builds on prior work published in Nature in 2015 which demonstrated that genetic disruption of ZIP12 abrogated the development of PH in hypoxic rats, while increased ZIP12 expression was also observed in affected pulmonary arteries from patients with PH. The new publication, titled “Targeting ZIP12-Mediated Zn²⁺ Signaling as a Treatment for Pulmonary Hypertension,” describes the progression of ZIP12 from a novel disease target identified through academic research to a Ph2-ready clinical candidate.

PH is a progressive and life-threatening disease characterized by increased pressure in the pulmonary circulation, which can arise from abnormalities in the pulmonary blood vessels, heart or lungs. In pulmonary arterial hypertension (PAH) and other forms of PH, progressive changes to the pulmonary vasculature increase pulmonary vascular resistance and place increasing strain on the right side of the heart, leading to heart failure. Although currently approved therapies have improved outcomes for patients, there remains a significant need for treatments that more directly address the underlying vascular pathology driving disease progression.

In the new paper, the authors show that increased ZIP12 expression in human pulmonary artery smooth muscle cells raises intracellular labile zinc, drives cell proliferation, and induces the metabolic reprogramming and Akt pathway activation characteristic of the hyperproliferative, apoptosis-resistant vascular cells found in PAH.

Building on these findings, Apollo developed APL-9796, a monoclonal antibody that binds the extracellular domain of ZIP12 and blocks zinc transport.

In human pulmonary vascular cells from patients with idiopathic PAH, APL-9796 normalized elevated intracellular zinc levels and reduced pathological cell proliferation and contractility. In three complementary and mechanistically distinct gold-standard preclinical models of pulmonary hypertension, APL-9796 demonstrated improvements across measures of pulmonary artery pressure, right ventricular hypertrophy, and pulmonary vascular remodeling.

“This publication provides a compelling target-to-clinic package for APL-9796 and highlights what we believe is a fundamentally differentiated opportunity in pulmonary hypertension,” said Dr. Richard Mason, CEO of Apollo Therapeutics. “ZIP12 inhibition is designed to address the abnormal vascular proliferation and remodeling that contribute to disease progression, rather than simply modulating vascular tone. The consistency of the findings across human PAH-derived cells and multiple disease models gave us a strong foundation to test this mechanism in patients. With APL-9796 now in Phase 2 development, the ViTAL-PH trial in patients with PH represents the next important step in establishing the clinical potential of this novel biology.”

The manuscript also reports results from a Phase 1 single-ascending-dose trial of APL-9796 in healthy adults. APL-9796 was administered subcutaneously across doses ranging from 0.3 mg/kg to 12 mg/kg and was well tolerated, with no safety concerns reported. The antibody demonstrated dose-dependent pharmacokinetics and a half-life supporting once monthly subcutaneous dosing.

APL-9796 is currently being evaluated in ViTAL-PH (NCT06846554), a Phase 2, multicenter, open-label, dose-escalation trial in adults with pulmonary hypertension. Part A is enrolling adults with WHO Group 1 PAH across three dose levels, and an optional Part B will enroll adults with WHO Group 3 PH associated with interstitial lung disease (PH-ILD). The trial uses continuous remote hemodynamic monitoring via telemetry from an implanted pulmonary artery sensor called CardioMEMS^® to assess the safety, tolerability, pharmacokinetics and hemodynamic effects of APL-9796 administered as an add-on to background therapy.

About APL-9796

APL-9796 is a first-in-class, humanized monoclonal antibody that inhibits ZIP12 (SLC39A12), a zinc transporter that is upregulated in the remodelled pulmonary vasculature of patients with pulmonary hypertension. By blocking ZIP12-mediated zinc influx, APL-9796 is designed to target the vascular cell proliferation and remodelling that drive disease progression – a mechanism distinct from approved therapies, which act primarily on vascular tone. APL-9796 was well tolerated in a Phase 1 trial in healthy participants and is currently in Phase 2 development in adults with pulmonary hypertension (ViTAL-PH; NCT06846554).

About Apollo Therapeutics

Apollo Therapeutics, a biopharmaceutical company focused on translating breakthrough science from top global universities into differentiated medicines, is based in the US and UK. With five programs in clinical development and multiple preclinical programs, Apollo is building a diversified portfolio of novel therapeutics with uncorrelated risk. Apollo has a scalable R&D platform enabled by an unprecedented level of access to breakthroughs in biology and basic medical research made at six of the world's leading universities and research institutes. Apollo also in-licenses or acquires clinical-stage programs where it has unique insights and synergies. For more information, please visit www.apollotx.com.

About Imperial College London

Imperial College London is a world-leading university focused on science, technology, engineering, medicine and business (STEMB). Founded in 1907, Imperial has a long history of scientific discovery and innovation, including pioneering advances such as penicillin, holography and fibre optics. Today, Imperial brings together exceptional teaching, world-class research and interdisciplinary collaboration to address some of the world's most pressing challenges, including global health, climate change, artificial intelligence and sustainable development. Through its global network of students, researchers and partners, Imperial is committed to translating scientific excellence into real-world impact. For more information, please visit https://www.imperial.ac.uk

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