..Author: Ben Eversfield

AdAlta Limited (ASX: 1AD), the biotechnology company advancing its lead i-body candidate towards clinical development today announced additional positive pre-clinical data for its lead drug candidate AD-114, a novel first-in-class drug candidate being developed to treat fibrosis, a condition prevalent in 45 to 50 per cent of all diseases.

The new data show the administration of AD-114 reduced fibrosis in therapeutic mouse models of both lung and liver fibrosis. In the mouse model of lung fibrosis, collagen deposition and collagen gene expression were both reduced in the lungs, after 14-days of i-body AD-114 treatment. Excessive collagen stiffens tissue, causing fibrosis. In the mouse model of liver fibrosis, serum alanine aminotransferase (ALT) levels and the non-alcoholic fatty liver disease (NAFLD) score were improved with the treatment of AD-114 for 21 days. Concentration of ALT in plasma is a biomarker for liver disease progression: the improvement in serum liver enzyme ALT levels suggests that the i-body ameliorated liver injury and inflammation. The NAFLD score improvement indicates AD-114 possesses hepatoprotective effects and therefore has potential for the treatment of non-alcoholic steatohepatitis (NASH).

Extensive pre-clinical AD-114 studies have demonstrated positive in vitro (in the lab) and in vivo (in animals) data. These new data validates a number of earlier studies and AdAlta has now demonstrated anti-fibrotic activity of AD-114 in animal models of lung, liver and eye fibrosis.

AdAlta Chief Executive Officer Sam Cobb said, “We are encouraged by these new pre-clinical data which supports the broad anti-fibrotic activity of AD-114 and the therapeutic use of AD-114 in the treatment of idiopathic pulmonary fibrosis and more broadly in other fibrosis diseases including liver fibrosis or NASH.

“AdAlta remains on track to meet its stated clinical development milestones and management remains focused on expediting AD-114 into Phase 1 human clinical trials for idiopathic pulmonary fibrosis by early 2018. Our strategy is to license this drug candidate on completion of the planned Phase 1 clinical studies.”

There is growing global interest in promising new treatments for fibrosis, especially for idiopathic pulmonary fibrosis, which has a 50 to 70 per cent mortality rate and affects 135,000 people in the US every year.

The data in the lung fibrosis mouse model will be used to support AdAlta’s application for orphan drug status for AD-114 for the treatment of idiopathic pulmonary fibrosis (IPF). Orphan Drug status allows for significant R&D tax credits, new drug application fee waivers and a seven year period of market exclusivity from the US Food & Drug Administration (FDA) after approval. Companies pursuing orphan treatments are usually granted accelerated development and regulatory timelines as well as premium pricing.

AdAlta Chief Scientific Officer Dr. Mick Foley, said, “The response and data observed with AD-114 is important for arresting and modulating a number of fibrosis related diseases and addressing the treatment of fibrotic conditions, including those of the lung and liver.

“While idiopathic pulmonary fibrosis (IPF) is the primary indication for AD-114, these data demonstrate the broad applicability of AD-114 for the treatment of multiple fibrosis related diseases including cirrhosis of the liver.”

“We believe the new data of AD-114 in animal models of lung and liver fibrosis add to a growing body of evidence to support AdAlta’s application to begin a Phase I clinical study in humans aimed at validating its promise in treating fibrosis, notably IPF and other fibrotic diseases, for which current therapies have limited efficacy and where there is a high-unmet medical need.

Full details of these new studies are available on the AdAlta website www.adalta.com.au.  The new data will be presented by AdAlta CEO Sam Cobb, along with other pre-clinical data on AD-114, at the Biotech Showcase 2017 conference in San Francisco at 9am on 11 January 2017 (Hilton Hotel – Room 3, Ballroom Level, Union Square, 333 O’Farrell Street, San Fran, CA 94102).

Notes to editors

About AdAlta Limited

AdAlta Limited (ASX:1AD) is an Australian based drug development company headquartered in Melbourne. The Company is focused on using its proprietary technology platform to generate i-bodies, a new class of protein therapeutics, with applications as therapeutic drugs to treat diseases.

AdAlta is developing its lead i-body candidate, AD-114, for the treatment of idiopathic pulmonary fibrosis (IPF) and other human fibrotic diseases, for which current therapies are sub-optimal and there is a high-unmet medical need. AD-114 has strong pre-clinical results for IPF, demonstrating both anti-fibrotic and anti-inflammatory activity in human lung tissue and indicating greater efficacy than existing approved IPF drugs.

The i-body is a human analogue of the antigen binding domain of the shark antibody, which combines the advantages of monoclonal antibodies (high target specificity and affinity) with the beneficial stability features of small molecules. In addition to stability, the i-body has a long binding loop that is a feature of shark antibodies not present in either human or next generation antibodies. This feature enables the i-body to recognise and bind to a diverse range of different therapeutically-relevant drug targets, including those that are difficult/intractable to access by current antibody therapies. These include clinically important targets such as G-protein coupled receptors (GPCRs) and ion channels.

The Company also plans to continue further drug discovery and development directed towards other drug targets and diseases with its i-body technology platform. Further information can be found at: www.adalta.com.au

Additional AD-114 lung fibrosis data

In a therapeutic mouse model of Bleomycin, a standard animal disease model used for the assessment of drug candidates for the treatment of pulmonary fibrosis, the administration of AD-114 markedly reduced the extent of collagen deposition in the lungs, as measured by Ashcroft score and hydroxyproline assay. Additionally, a reduction in collagen (both Col1A and Col3A) gene expression was also noted after 14-days of i-body treatment. Excessive collagen stiffens tissue, causing fibrosis. These additional pre-clinical data supports the anti-fibrotic activity of AD-114 and support the therapeutic use of AD-114 in the treatment of IPF.

This additional data will be used to support AdAlta’s application for orphan drug status for AD-114 for the treatment of idiopathic pulmonary fibrosis (IPF). IPF is a chronic, lethal and rare disease with a 50 to 70 per cent mortality rate. It currently affects at least 135,000 people in the US annually and a high-unmet medical need. Orphan Drug status allows for large R&D tax credits, NDA fee waivers, and seven years’ market exclusivity from the US FDA after approval. Companies pursuing orphan treatments are usually granted accelerated development and regulatory timelines as well as premium pricing.

AD-114 liver fibrosis data

AD-114 decreased serum alanine aminotransferase (ALT) levels to 43U/L from 64U/L in the vehicle, a 33% reduction. The improvement in serum ALT levels suggests that i-body ameliorated hepatocellular injury and inflammation. Concentration of liver enzyme (ALT) in the plasma is a biomarker for liver disease progression. AD-114 also reduced the non-alcoholic fatty liver disease (NAFLD) score compared with the vehicle or diseased group. Hepatocyte ballooning was also significantly decreased compared with the vehicle or diseased group. AD-114 possesses hepatoprotective and anti-NASH effects.

Nonalcoholic steatohepatitis (NASH) is liver inflammation and damage caused by a buildup of fat in the liver, inflammation and fibrosis. NASH can get worse and the progressive fibrosis or scarring of the liver leads to cirrhosis. NASH affects 70-90% of obese or diabetic populations, and overall, NASH affects 3-5% of the US population, for which there are no treatments currently approved.

Contact:

At AdAlta

Sam Cobb
Chief Executive Officer
AdAlta Limited
Tel: +61 (0) 3 9479 5159
E: s.cobb@adalta.com.au

Media (Australia)
Andrew Geddes
Tel: +61 (0) 408 677 734
E: adalta@instinctif.com

Media (International)
Sue Charles/Daniel Gooch
Tel: +44 (0) 20 7866 7905
E: adalta@instinctif.com

MELBOURNE, Australia, 15^th November 2016: AdAlta Limited (ASX: 1AD), the biotechnology company advancing its lead i-body candidate towards clinical development today announced the appointment of San Diego-based Dr Robert Peach as Non-Executive Director effective from 15^th November 2016.

Dr Peach was co-founder and Chief Scientific Officer of Receptos Inc., a company developing a promising drug for patients with relapsing multiple sclerosis, inflammatory bowel disease, and other autoimmune diseases. Receptos listed on NASDAQ until it was acquired by Celgene Corporation in 2015 for US$7.8bn in cash. Dr Peach has deep experience in research and drug development, having held senior executive and scientific positions in biotechnology companies such as Apoptos Inc., Biogen Idec, Idec Pharmaceuticals Corporation, and Bristol-Myers Squibb Pharmaceutical Research Institute. Dr Peach received a BSc and MSc (1st class honours) from the University of Canterbury and a PhD in Biochemistry from the University of Otago, New Zealand.

AdAlta Chairman Paul MacLeman said, “AdAlta is fortunate to have attracted someone with Robert’s skills at monetarising science to join the Board. His drug development and international industry experience are aligned with AdAlta’s goals.

About AdAlta LImited

AdAlta Limited (ASX:1AD) is an Australian based drug development company headquartered in Melbourne. The Company is focused on using its proprietary technology platform to generate i-bodies, a new class of protein therapeutics, with applications as therapeutic drugs to treat disease.

AdAlta is developing its lead i-body candidate, AD-114, for the treatment of idiopathic pulmonary fibrosis (IPF) and other human fibrotic diseases, for which current therapies are sub-optimal and there is a high-unmet medical need. AD-114 has strong pre-clinical results for IPF, demonstrating both anti-fibrotic and anti-inflammatory activity in human lung tissue and indicating greater efficacy than existing approved IPF drugs.

The i-body is a human analogue of the antigen binding domain of the shark antibody, which combines the advantages of monoclonal antibodies (high target specificity and affinity) with the beneficial stability features of small molecules. In addition to stability, the i-body has a long binding loop that is a feature of shark antibodies not present in either human or next generation antibodies. This feature enables the i-body to recognise and bind to a diverse range of different therapeutically-relevant drug targets, including those that are difficult/intractable to access by current antibody therapies. These include clinically important targets such as G-protein coupled receptors (GPCRs) and ion channels.

The Company also plans to continue further drug discovery and development directed towards other drug targets and diseases with its i-body technology platform.

Melbourne, Australia, and Utrecht, the Netherlands, 8th November 2016: AdAlta Limited (ASX: 1AD), a biotechnology company specialising in the discovery and development of protein-based therapeutics, and Crossbeta Biosciences, a biotechnology company with unique technology for therapeutic and diagnostic use in neurodegenerative disorders, today announced their commercialisation agreement.

Under the terms of the agreement, Crossbeta has been granted an exclusive license to three beta-amyloid oligomer (AßO)-specific shark antibodies, identified under the collaboration signed between AdAlta and Crossbeta in December 2013. These shark antibodies are considered to have immediate and highly disease-specific potential for the diagnosis and treatment of Alzheimer’s disease.

AdAlta will receive royalties on future revenues from successful commercialization of the AßO-specific shark antibodies as novel therapeutics or diagnostic agents. All ongoing research and development (R&D) as well as commercialisation will be managed by Crossbeta.

Combining the unique strengths of both companies, the R&D collaboration used AßOs produced by Crossbeta’s proprietary oligomer-stabilising technology and AdAlta’s single-domain shark antibody library was used to screen these novel targets to identify the therapeutic and diagnostic lead candidates.

The three licensed anti-AßO antibodies bind specifically to the disease-relevant AßO preparation, but, importantly, do not recognize or bind to the monomer and fibrils of the beta-amyloid protein.

AdAlta Chief Executive Officer Samantha Cobb said: “Crossbeta’s novel and unique oligomer-stabilisation technology enabled us to identify Alzheimer’s disease-specific shark single domain antibodies with highly valuable differential binding properties. The long loop of the shark single domain antibody (or i-body) binds to unusual epitopes with high affinity and specificity, as demonstrated with our lead candidate to a GPCR and previous targets and, most recently, in this instance with Crossbeta’s AßOs. This licensing deal fits with our strategy to focus on the i-body platform and our lead candidate in fibrosis and we believe that Crossbeta with its strong position in the therapeutic area of Alzheimer’s is the right partner to realize the potential of these novel antibodies.”

Crossbeta Biosciences Chief Executive Officer Guus Scheefhals said: “We are very pleased with the outcome of our collaborative agreement with AdAlta, exploiting the promising characteristics of our AßOs to the future benefit of the Alzheimer’s field and patients. We will now move forward with developing these novel anti-AßO antibodies as potential treatments of real disease-modification potential and diagnostic use, as early in the disease as possible, for the benefit of Alzheimer’s patients.”

Alzheimer’s is the most common form of dementia, primarily affecting people above the age of 60. Alzheimer’s disease affects about 1 in 10 people over 65 years, and more than 1 in 4 people over 85 years. Alzheimer’s is an area of unmet medical need with a significant social and economic impact.

Notes to editors

About AdAlta

AdAlta Limited is an Australian based drug development company headquartered in Melbourne. The Company is focused on using its proprietary technology platform to generate i-bodies, a new class of protein therapeutics, with applications as therapeutic drugs to treat disease.

The i-body is a human analogue of the antigen binding domain of the shark antibody, which combines the advantages of monoclonal antibodies (high target specificity and affinity) with the beneficial stability features of small molecules. In addition to stability, the i-body has a long binding loop that is a feature of shark antibodies not present in either human or next generation antibodies. This feature enables the i-body to recognise and bind to a diverse range of different therapeutically-relevant drug targets, including those that are difficult/intractable to access by current antibody therapies. These include clinically important targets such as G-protein coupled receptors (GPCRs) and ion channels.

AdAlta is developing its lead i-body candidate, AD-114, for the treatment of idiopathic pulmonary fibrosis (IPF) and other human fibrotic diseases, for which current therapies are sub-optimal and there is a high-unmet medical need.

The Company also plans to continue further drug discovery and development directed towards other drug targets and diseases with its i-body technology platform.

Further information can be found at: www.adalta.com.au

About Crossbeta Biosciences
Crossbeta Biosciences is a biotech company with a proprietary technology for efficient oligomer-based drug discovery, with applications in Alzheimer’s, Parkinson’s, ALS and Huntington’s disease. Crossbeta’s technology allows the unprecedented generation of well-defined stable, pathobiologically functional, oligomers. Crossbeta’s oligomers have enabled the development of robust assays allowing fast, de-risked compound screening and characterization. The unique capabilities of Crossbeta’s technology have been demonstrated in a therapeutic Alzheimer’s disease program by successfully identifying compounds that neutralize oligomer toxicity in vitro and in vivo.

Crossbeta offers its proprietary technology for strategic collaborative partnerships aimed at developing new oligomer targets and related screening assays and for therapeutic and diagnostic/biomarker assay development programs.

Further information can be found at: www.crossbeta.com
For Further information

At AdAlta

Sam Cobb
Chief Executive Officer
AdAlta Limited
Tel: +61 (0) 3 9479 5159
E: s.cobb@adalta.com.au

Media (Australia)
Andrew Geddes
Tel: +61 (0) 408 677 734
E: adalta@instinctif.com

Media (International)
Sue Charles/Daniel Gooch
Tel: +44 (0) 20 7866 7905
E: adalta@instinctif.com

At Crossbeta Biosciences

Guus Scheefhals, CEO
Crossbeta Biosciences BV
Tel: +31 30 253 2668
E: g.scheefhals@crossbeta.com

Melbourne, Australia and FREISING, Germany, 7 November 2016: AdAlta Ltd (ASX: 1AD), the biotechnology company advancing its lead i-body candidate towards clinical development, and XL-protein GmbH, a privately owned German biopharmaceutical company specialized in the design of biobetters with extended half-life, announced today that they have entered into a collaboration on the development and commercialization of a long acting form of AD-114, a novel first-in-class drug candidate for fibrosis therapy.

Under this collaboration agreement, XL-protein will apply its proprietary PASylation^® technology to AD-114 to extend its circulation half-life and, thus, duration of therapeutic action. AD-114 is AdAlta’s lead i-body drug candidate being developed for the treatment of idiopathic pulmonary fibrosis (IPF) and a variety of other fibrotic and inflammatory diseases. In preclinical studies of IPF, the initial indication for AD-114, the i-body has shown both anti-fibrotic activity as well as anti-inflammatory activity, which are important for the treatment and prevention of this disease.

A long-acting form of AD-114 that has a significantly extended plasma half-life would allow less frequent administration and lower dosing, making it ideal for treating chronic indications such as IPF.

XL-protein’s PASylation^® technology offers a biological alternative to PEGylation, an established chemistry procedure that is used to modify and tailor residence time of protein drugs in blood plasma.

The PASylation^® technology utilizes genetic engineering to fuse a polymer of natural amino acids (Proline, Alanine and/or Serine) with a protein-based therapeutic such as AD-114, thereby enabling manufacture of a fully active protein in various host organisms, including the laboratory bacterium Escherichia coli. The PASylation^® approach not only provides a tunable plasma half-life that is related to the length of the PAS polymer but also offers traceless metabolization.

“XL-protein is providing a smart, biological approach to enable precise modifications to AD-114 that are designed to prolong its circulation time in the body and therefore window of activity. We are excited to be working with the XL-protein team as we aim to progress AD-114 towards the clinic by early 2018” said Sam Cobb, CEO of AdAlta.

“We are pleased to report that preliminary data from pilot studies in animal models look promising as this shows that the plasma half-life of AD-114 has been dramatically extended. In terms of manufacturing, this modification is easily incorporated into AD-114, allowing facile scale-up and downstream purification” commented Claus Schalper, CEO of XL-protein.

Financial terms have not been disclosed.

About AdAlta LImited

AdAlta Limited (ASX:1AD) is an Australian based drug development company headquartered in Melbourne. The Company is focused on using its proprietary technology platform to generate i-bodies, a new class of protein therapeutics, with applications as therapeutic drugs to treat diseases.

AdAlta is developing its lead i-body candidate, AD-114, for the treatment of idiopathic pulmonary fibrosis (IPF) and other human fibrotic diseases, for which current therapies are sub-optimal and there is a high-unmet medical need. AD-114 has strong pre-clinical results for IPF, demonstrating both anti-fibrotic and anti-inflammatory activity in human lung tissue and indicating greater efficacy than existing approved IPF drugs.

The i-body is a human analogue of the antigen binding domain of the shark antibody, which combines the advantages of monoclonal antibodies (high target specificity and affinity) with the beneficial stability features of small molecules. In addition to stability, the i-body has a long binding loop that is a feature of shark antibodies not present in either human or next generation antibodies. This feature enables the i-body to recognise and bind to a diverse range of different therapeutically-relevant drug targets, including those that are difficult/intractable to access by current antibody therapies. These include clinically important targets such as G-protein coupled receptors (GPCRs) and ion channels.

The Company also plans to continue further drug discovery and development directed towards other drug targets and diseases with its i-body technology platform.

Further information can be found at: www.adalta.com.au

About XL-protein GmbH

XL-protein is a German biotech company commercializing the ground-breaking PASylation^® technology, which enables the design of biopharmaceuticals with extended plasma half-life and enhanced action. With its strong proprietary technology position XL-protein focuses at the preclinical as well as clinical development of PASylated proteins and peptides in various disease areas. The company is enganged in several biological drug programs with renowned pharma partners.

Further information can be found at: www.xl-protein.com

About PASylation^®

Rapid kidney clearance is a drawback of most therapeutic proteins and peptides. Conformationally disordered polypeptide chains with large hydrodynamic volume made of the L-amino acids Pro, Ala, and/or Ser (PAS) provide an alternative to chemical conjugation with PEG in order to extend the plasma half-life of biologics. PAS sequences are hydrophilic, uncharged biological polymers with PEG-like biophysical properties. In contrast, beside chemical coupling PAS polypeptides offer simple fusion to a biological drug at the genetic level as well as biodegradability, thus preventing tissue accumulation. PASylation has been successfully applied to a series of biopharmaceuticals, including interferon, leptin, exendin, coagulation factors, lipocalins and Fab fragments, yielding several drug candidates currently on the route towards clinical study.

 

Contact:

AdAlta Limited 

Sam Cobb, CEO
Tel: +61 (0) 3 9479 5159
E: s.cobb@adalta.com.au

XL-protein GmbH

Claus Schalper, CEO
Tel: +49-8161-53730-90
E: bd@xl-protein.com