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The first patient has been dosed in the multi-center UK Phase 2 clinical trial (ViTAL-PH) of APL-9796 at the Hammersmith Hospital in London, part of Imperial College Healthcare NHS Trust.

APL-9796 is a first-in-class anti-ZIP12 mAb being developed as a disease modifying therapeutic for pulmonary hypertension with the aim of reversing the pulmonary artery wall thickening (vascular remodelling) that drives the disease.

Every year Pulmonary Hypertension (PH) patient groups and organisations across the globe participate in World Pulmonary Hypertension Day (May 5) to raise awareness of PH and celebrate the lives of people living with the condition.

PH is a chronic, progressive, and often debilitating condition that can ultimately lead to heart failure. The condition leads to the narrowing and stiffening of blood vessels in the lungs, a process known as pulmonary vascular remodelling, placing significant strain on the heart as it tries to pump blood through the lungs. People living with PH commonly experience breathlessness, fatigue, and reduced quality of life. Current treatments on the market primarily address symptoms rather than the underlying cause, and unfortunately, the long-term outlook for people with PH remains poor with approximately 30% of patients surviving less than three years post diagnosis.

One of Apollo Therapeutics’ five programs currently in clinical development, APL-9796 is a first-in-class, exquisitely selective, anti-ZIP12 monoclonal antibody (mAb) which is being developed as a potential disease modifying therapeutic for PH that aims to reverse the vascular remodelling that drives the disease. APL-9796 was identified following a comprehensive design, synthesis and screening campaign led by Apollo Therapeutics. The APL-9796 program was established through the company’s research collaboration with Imperial College London, one of the six world leading universities and research institutes that Apollo Therapeutics has a unique partnership agreement with.

Following recent confirmation of the safety and tolerability of APL-9796 in a Phase 1 trial conducted in healthy participants, the team at Apollo Therapeutics designed an innovative clinical trial, called ViTAL-PH, in collaboration with key experts in the field to evaluate APL-9796 for the first time in patients with PH. There are several different types of PH, and the ViTAL-PH trial is initially focused on patients with pulmonary arterial hypertension (WHO Group I) and PH due to hypoxic lung conditions (WHO Group III).

The current Phase 2 trial is recruiting PH patients with Abbott CardioMEMS^TM implants that remotely monitor pulmonary artery pressures to evaluate the efficacy of APL-9796 in near real time and with each patient acting as their own control against baseline measurements. During April 2025, the first PH patient in the Phase 2 ViTAL-PH clinical trial of APL-9796 was dosed at the Hammersmith Hospital in London, part of Imperial College Healthcare NHS Trust. As the trial continues, it will recruit patients at other centers across the UK specialising in the treatment of PH.

 “Our APL-9796 program is a perfect example of the model we are deploying at Apollo Therapeutics, where we work with academics at the world’s top universities such as Imperial College London in order to translate their breakthroughs in basic science into new therapies for major diseases,” said Richard Mason, Chief Executive Officer of Apollo Therapeutics. “What is particularly exciting for this program is that we went full circle – translating an important scientific discovery out of Imperial College into a new therapeutic candidate and then dosing the first patient with the candidate at the Hammersmith Hospital, a teaching hospital within the Imperial College NHS Healthcare Trust. We look forward to progressing APL-9796 through the clinic as a potential treatment option for people suffering from PH, where current treatments do not treat the underlying cause of their disease.”

A deeper overview of the research and science behind APL-9796
ZIP12¹ is a zinc transporter protein that plays a crucial role in pulmonary vascular remodelling (pulmonary artery wall thickening), particularly in response to low oxygen as well as other noxious stimuli. Previous research led by Professor Martin Wilkins and Dr Lan Zhao from the Department of Medicine at Imperial College London published in Nature in 2015² identified ZIP12 as a potential drug target for treating PH that may reverse the pulmonary vascular remodelling that drives the disease. After observing how pulmonary arterial pressures vary between different human highlander populations living at altitude, the Imperial team searched for a potential gene responsible for this variation. A gene was subsequently identified in a type of rat that is resistant to developing pulmonary hypertension in a low oxygen atmosphere. It is responsible for producing a protein called ZIP12, which regulates zinc levels in cells. Disabling this gene helps protect normal rats against pulmonary hypertension in low oxygen conditions. ZIP12 is not present or active in normal human lungs but has been shown to be detectable and switched on in the lungs of patients with pulmonary hypertension.

Preclinical research conducted by Apollo Therapeutics in collaboration with Imperial College London demonstrated APL-9796 has disease-modifying potential in gold standard rodent PH models. These models mimic the histological and physiological characteristics of clinical PH, with thickened and stiff blood vessels in the lungs resulting in increased pressure and poor cardiac output. APL-9796 reversed the thickening of the vessels, reduced the pressure, and reduced the damage to the right ventricle of the heart which improved cardiac output in these model systems.

¹ ZIP12 (SLC39A12) is a non-voltage gated zinc ion (Zn2+) transporter belonging to the solute carrier gene family
² Zhao et al (2015), “The zinc transporter ZIP12 regulates the pulmonary vascular response to chronic hypoxia”, Nature, doi:10.1038/nature14620

About Apollo Therapeutics Group Limited

Apollo Therapeutics (“Apollo”) is a portfolio biopharmaceutical company based in the UK and USA. Apollo translates breakthroughs in biology and basic medical research into innovative new medicines. With over 20 active therapeutic programs, five of which are in clinical development, the company is building a large, 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. The company also in-licenses or acquires clinical-stage programs where it has unique insights and synergies. Backed by leading specialist health care investors, Apollo has raised a total of over $450m since its inception. Visit www.apollotx.com.