As part of an education series, AdAlta is explaining a range of debilitating diseases, including fibrosis. This post will focus on kidney fibrosis.
🔍 Let’s look at kidney fibrosis
Fibrosis is a condition where excessive scar tissue forms as a result of inflammation or damage, hindering normal functions. The kidney’s main job is to clean your blood, filtering any waste out through your urine. When your kidneys aren’t functioning properly, waste gradually builds up in your body, which can impact your health in many ways. This can lead to ‘chronic kidney disease’, where there is a loss of normal kidney function for more than three months.
Kidney fibrosis, also known as renal fibrosis, may be caused by chronic kidney disease or by the failed or incomplete healing of the kidney tissue after an acute injury. This causes the kidneys to stop working and eventually leads to the need for a transplant.
Kidney fibrosis occurs when there is an imbalance between the formation and degradation of the ‘extracellular matrix’, which is the network of proteins that provides support to the kidneys. As fibrosis progresses, the scar tissue replaces healthy kidney tissue, impairing the proper functioning of the kidneys.
Kidney fibrosis is a progressive process that ultimately leads to end-stage renal disease (ESRD). Treatments can include lifestyle and dietary changes at early stages, to keep blood pressure and blood glucose levels at safe levels. In later stages, treatments can include kidney transplantation or kidney replacement therapy (dialysis).
AdAlta has demonstrated that the lead candidate, AD-214, has broad anti-fibrotic effects in the lung, kidney and eye. As at October 2023, AD-214 is undergoing a Phase 1 extension clinical study, designed to assess the safety and availability of multiple 10 mg/kg intravenous doses of AD-214, which is the highest dose anticipated to be used in forthcoming Phase II clinical studies. We expect to report interim data by the end of 2023 and full data in early 2024.
As part of an education series, AdAlta is explaining a range of debilitating diseases, including fibrosis. Given that September is Pulmonary Fibrosis Awareness Month, this post will focus on fibrosis of the lungs, and more specifically, Pulmonary Fibrosis.
🔍 More on lung fibrosis
Fibrosis is a condition where excessive scar tissue forms as a result of inflammation or damage, hindering normal functions. A specific form of lung fibrosis is Idiopathic Pulmonary Fibrosis (IPF), where tissues deep in the lungs experience a build-up of fibrous connective tissues which cause the walls of the lungs to thicken, resulting in a progressive decline in lung function, and shortness of breath. Sufferers often feel like they are in danger of suffocating, as they are constantly short of breath.
🔍 Fibrosis facts
There is no cure for IPF
>490,000 people live with IPF globally
In Australia, IPF affects about 5,000 people
While still a rare disease, in the US >40,000 people die every year from IPF
The median survival after diagnosis is 3.8 years
88% of sufferers are aged 55 or older
IPF is a US$4.3b industry
There are two current therapies, with limited effectiveness and serious side effects
Because this condition affects less than one in 20,000 patients within the USA or Europe, any drugs addressing it are called orphan drugs.
In 2021, AdAlta was granted “Orphan Drug Designation” by the FDA in the US. This allows for new drug application fee waivers, a potentially faster route to market and an additional seven years of exclusivity once a drug is on market.
AdAlta’s solution: AD-214 is currently undergoing a Phase I extension study, with the goal of confirming the safety and dosing schedule, reducing the duration and cost of Phase II studies.
Current status of AD-214:
Pre-clinical efficacy in multiple animal models of fibrotic disease = multiple indication potential
Manufacturing process established
Phase I successfully completed = well tolerated, evidence of target binding
Strong intellectual property protection = asset protection to 2036
Regulatory advantages = US FDA Orphan Drug Designation
A video series covering the 2020 Investor Briefing, where senior leaders from AdAlta reviewed the three significant recent achievements for a lead product candidate, AD-214, and AdAlta’s strategic program.
CEO Update Investor Briefing March 2020
AdAlta Chief Executive Officer & Managing Director, Dr Tim Oldham, discusses AdAlta’s recent milestones, vision and strategic plans.
Individual Speaker Presentations
Welcome announcement
AdAlta Chair, Paul MacLeman introduces the 2020 Investor Briefing and reviews three significant recent achievements for lead product candidate, AD-214.
Vision and strategic goals
AdAlta CEO, Tim Oldham summarises the AdAlta vision and strategic plan, presents a case study illustrating what is required to realise the plan, and describes the key strategic priorities and metrics that will drive success. AdAlta’s purpose is to use its i-body platform to develop novel protein therapeutics against drug targets that have proven difficult to drug with traditional antibodies. In order to maximise the number of drugs developed from the i-body platform, AdAlta will develop an internal pipeline of drugs targeting GPCRs in fibrosis, inflammation, and oncology and enter co-development partnerships for drugs against other difficult targets and in other therapeutic areas. Near term priorities are: progress AD-214 into clinical trials and expand indications; develop an internal pipeline of 5 product candidates targeting GPCRs; develop an external pipeline through 3-5 co-development partnerships, and continue to invest in improving the i-body platform and AD-214 product.’
AD-214: pre-clinical update and PET tracer
AdAlta CSO, Mick Foley describes the significance of three significant recent achievements: winning a $1m competitive grant to develop a radio-labeled version of AD-214 to enable PET imaging in patients, significantly improving the value of our Phase I program; demonstrating efficacy of AD-214 in the gold standard animal model of Idiopathic Pulmonary Fibrosis (IPF), enabling progress into Phase I trials; and demonstrating that AD-214 binds to its target, CXCR4, for longer than the circulating half-life in blood plasma, going confidence that a weekly or longer dosing schedule may be possible and confirming the Phase I dosing schedule. Professor Foley also describes the work AdAlta is doing to extend indications for AD-214 beyond IPF.
AD-214: Phase 1 clinical strategy
AdAlta’s Vice-President Clinical Product Development, Claudia Gregorio-King discusses the two-part Phase I program for AD-214 incorporating an initial healthy volunteer cohort and then rapidly moving to patients with fibrotic interstitial lung disease (ILD) including IPF. Dr Gregorio-King also reviews potential Phase II trial size and scope.
Pipeline and partnership expansion
AdAlta CEO, Tim Oldham describes AdAlta’s sweet spot for internal projects (drugs acting on GPCRs implicated in fibrosis, inflammation or oncology where the GPCR has been validated as a disease target and previous attempts to drug the target have been unsuccessful); the describes the processes for selecting these projects, securing co-development partnerships on other targets and out-licensing internal projects such as AD-214.
Continuous i-body platform and AD-214 product improvement
AdAlta COO, Dallas Hartman, outlines strategies for continuous improvement of the i-body platform (to extend intellectual property and improve discovery efficiency and manufacturability of discovered i-bodies); and for continuous improvement of AD-214 processes and formulations to maximise the number of indications and dose levels for which the drug can be used.
Staging growth
AdAlta CEO, Tim Oldham brings the strategic themes together into a roadmap for R&D and financing for the next three years. The roadmap comprises a near term focus on maximising data generated as AD-214 moves into the clinic for the healthy volunteer part of the Phase I program, catalysing growth options; an expansion of these options during the second part of the AD-214 program through investments in i-body2.0, new indication proof of concept and initial discovery on new targets; and acceleration of growth as major investments in the internal pipeline are made and partnering efforts come to fruition.
