Rentschler Biopharma and XL-protein demonstrate efficient production of a hyperactive PASylated DNase I with extended half-life

  • Hyperactive DNase I modified with XL-protein’s PASylation® technology demonstrated significantly extended systemic half-life in vivo, potentially offering improved treatment options for autoimmune diseases and cystic fibrosis.
  • Potential for high-yield manufacturing of other PASylated protein therapeutics in mammalian cell culture on Rentschler Biopharma’s bioprocessing platform.

Laupheim and Freising, Germany, October 26, 2021 – Rentschler Biopharma SE, a leading global contract development and manufacturing organization (CDMO) for biopharmaceuticals, and XL-protein GmbH, a privately owned biopharmaceutical company located in Germany, announce a successful collaboration to manufacture a long-acting, hyperactive recombinant human deoxyribonuclease I (DNase I). Combining XL-protein’s proprietary PASylation® technology and Rentschler Biopharma’s expertise in bioprocess development, a process was developed with enhanced yield for a modified DNase I showing both strongly increased activity and an extended pharmacokinetic profile. This PASylated DNase I may open better treatment options for patients suffering from inflammation, chronic or autoimmune diseases.

“This highly successful collaboration was due to Rentschler Biopharma’s strong expertise along the entire biopharmaceutical value chain ranging from cell line development, upstream and downstream processes to drug substance manufacturing in combination with XL-protein’s know-how and longstanding experience in the design of proteins with enhanced stability using its proprietary PASylation technology. The strong results from this case study pave the way for high yield manufacturing of other PASylated proteins and peptide drugs using mammalian cell culture on Rentschler Biopharma’s bioprocessing platform,” said Thilo Grob, Vice President Process Science at Rentschler Biopharma SE.

Dr. Michaela Gebauer, Co-Managing Director at XL-protein, commented: “PASylation technology is compatible with efficient production in diverse expression hosts, and we now have shown that it can be applied to Rentschler Biopharma’s robust high titer mammalian cell line development platform which also allows for native post-translational modification of recombinant human proteins. This success further demonstrates the strength and flexibility of our technology platform and its potential to support biopharmaceutical partners seeking to develop recombinant protein or peptide drugs with extended half-life and low immunogenicity.”

Therapeutic DNase I has been used for more than 20 years to treat cystic fibrosis and holds the potential to be a promising treatment option for chronic as well as autoimmune diseases or inflammation. However, the short half-life of conventional DNase I requires high dosing frequency, which may result in low patient compliance and, in the case of cystic fibrosis, can lead to an elevated risk of lung infections. The improved DNase I manufactured collaboratively by Rentschler Biopharma and XL-protein has demonstrated both extended systemic half-life in an animal model and increased enzymatic activity. While its DNA-degrading activity is associated with a burden for the producing cell line, the high titer of recombinant protein achieved in the bioprocess is a remarkable success. The clinical application of this PASylated hyperactive DNase I could potentially offer improved patient adherence and better quality of life.

Meet Rentschler Biopharma at PEGS Europe, Protein & Antibody Engineering Summit, November 2 – 4, 2021, Barcelona, Spain

  • A poster titled “Development of a Production Cell Line for PASylated Human DNase I with Extended Half-life” will be presented by Serge M. Stamm, Group Leader Production
  • A talk titled “Unleashing the full potential of therapeutic protein production with a state-of the-art expression platform” will be presented by Lucia Kirchgeorg, Director Business Development, on November 3 in the track Optimizing Expression Platforms at 9:30 a.m. CET
  • Federico Pollano, Senior Vice President Business Development, and his team are looking forward to meeting you at booth 304

About PASylated DNase I and PASylation® technology
PASylation® technology offers a biological alternative to PEGylation. The PASylated DNase I was generated using gene constructs encoding a hyperactive DNase I fused with an N-terminal PAS polypeptide comprising the small natural L-amino acids Pro, Ala and Ser in a defined sequence. The resulting modified DNase I demonstrated expanded hydrodynamic volume and a strongly extended pharmacokinetic profile in an animal model.

About Rentschler Biopharma SE
Rentschler Biopharma is a leading contract development and manufacturing organization (CDMO) focused exclusively on client projects. The company offers process development and manufacturing of biopharmaceuticals as well as related consulting activities, including project management and regulatory support. Rentschler Biopharma’s high quality is proven by its long-standing experience and excellence as a solution partner for its clients. A high-level quality management system, a well-established operational excellence philosophy and advanced technologies ensure product quality and productivity at each development and manufacturing step. In order to offer best-in-class formulation development along the biopharmaceutical value chain, the company has entered into a strategic alliance with Leukocare AG. Rentschler Biopharma is a family-owned company with about 1,100 employees, headquartered in Laupheim, Germany, with a second site in Milford, MA, USA. In Stevenage, UK, Rentschler Biopharma has launched a company dedicated to cell and gene therapies, Rentschler ATMP Ltd. For further information, please visit www.rentschler-biopharma.com.

Follow Rentschler Biopharma on LinkedIn and Facebook.

About XL-protein GmbH
XL-protein is a German biotech company commercializing its ground-breaking PASylation® technology, which enables the design of biopharmaceuticals with extended half-life and enhanced pharmacological action. Based on a strong proprietary technology position, XL-protein focuses at the preclinical as well as clinical development of PASylated proteins in diverse disease areas. XL-protein is engaged in a growing number of partnerships with international pharmaceutical and biotech companies at various levels.

For more information, please visit: www.xl-protein.com.

Download full press release:

Download pdf

XL-protein announces the Avi-PA(S)™ MAb platform to boost the preclinical and clinical development of therapies using its PASylation® technology

FREISING, GERMANY, July 12, 2021 – XL-protein GmbH, a German biotech company specialised in the development of biopharmaceuticals with extended half-life, announced today that key scientific data have been published in the Journal of Molecular Biology (2021, Vol. 433, Pub. no. 167113). The Open Access Publication “Molecular recognition of structurally disordered Pro/Ala-rich sequences (PAS) by antibodies involves an Ala residue at the hot spot of the epitope” is also available for download at XL-protein’s web site (http://www.xl-protein.com/key-publications).

PASylation® technology is based on the conjugation of pharmaceutically active compounds with a conformationally disordered polypeptide of defined sequence comprising the small natural amino acids Pro, Ala, and/or Ser, resulting in drastically enhanced stability in vivo. With its ground-braking technology XL-protein addresses a major limitation of biopharmaceutical proteins and peptides that often show fast clearance from circulation via kidney filtration, which strongly hampers efficacy in human therapy. PAS sequences are hydrophilic, uncharged, genetically encodable amino acid polymers. These PAS chains are conformationally disordered and occupy highly expanded hydrodynamic volume, thus showing biophysical properties very similar to poly-ethylene glycol (PEG) whose conjugation to drugs is a well-known method for plasma half-life extension.

PASylation® can be applied via genetic fusion or chemical coupling to many classes of pharmacologically active compounds, including proteins, peptides and low molecular weight drugs as well as nanoparticles, both for therapeutic purposes and in vivo diagnostics. PAS-drug conjugates show retarded kidney filtration and drastically prolonged pharmacokinetics (PK) in vivo. Likewise, PASylation leads to extended residence in the eye, where elimination of biopharmaceuticals also is strongly size-dependent, thus offering prospects for ophthalmology. The intrinsically uncharged PAS polypeptides do not interfere with the pharmacological activity of the drug component and show high stability in plasma as well as poor immunogenicity, while undergoing quick degradation and metabolization after cellular uptake. Therefore, PASylation® offers an attractive solution in applications with increased risk of PEG hypersensitivity.

With multiple projects heading towards clinical application and increasing interest from scientists in the biomedical area (as documented by a growing number of publications reporting the beneficial use of PASylation®) XL-protein succeeded in developing Avi-PA(S)™ MAbs as useful antibody tools for the preclinical as well as clinical development of PASylated drug candidates. XL-protein now offers these valuable immunochemical reagents to promote broader research on applications of PASylation® technology: https://xl-protein.com/shop

– End –

About XL-protein GmbH

XL-protein is a German biotech company commercializing its ground-breaking PASylation® technology, which enables the design of biopharmaceuticals with extended in vivo half-life and enhanced action. Based on a strong proprietary technology position, XL-protein focuses at the preclinical as well as clinical development of PASylated drug candidates in diverse disease areas. XL-protein is engaged in a growing number of partnerships with international pharmaceutical and biotech companies at various levels.

Download full press release:

Download pdf

XL-protein and Antlia Bioscience Announce Collaboration to Develop Long-acting Peptide Therapy of Chronic Heart Failure using PASylation® Technology

SAN DIEGO, U.S.A., and FREISING, Germany, 15th October, 2020: Antlia Bioscience, Inc., a privately owned biopharmaceutical company located in San Diego, California, and XL-protein GmbH, a privately owned biopharmaceutical company located in Germany, are pleased to announce a Strategic Alliance using XL-protein’s proprietary PASylation® technology for plasma half-life extension to develop a novel, long-acting, peptide therapeutic treatment for chronic heart failure. Brian Johnson, Antlia Bioscience’s CEO commented, “chronic heart failure is a significantly unaddressed medical condition and a major public health concern. XL-protein’s PASylation® technology will allow us to safely and effectively translate our peptide into a meaningful therapeutic option for patients with chronic heart failure. “PASylation® is an excellent biological solution for plasma-half extension of therapeutic peptides, and we believe that PASylation® offers a simpler manufacturing process and superior pharmacological properties,” commented Claus Schalper, CEO of XL-protein. “We are excited to work with Antlia Bioscience to further exploit the potential of our technology and to develop new therapeutic options for the treatment of chronic heart failure.” Financial terms of the agreement have not been disclosed.

About PASylation® Technology

‘PASylation’ involves the genetic fusion or chemical conjugation of a therapeutic protein or pharmaceutically active compound with a conformationally disordered polypeptide of defined sequence comprising the small natural amino acids Pro, Ala, and/or Ser. Due to the biophysical size effect, the typically rapid clearance via renal filtration of the original drug can be retarded by a factor 10-100, depending on the length of the PAS chain. PAS sequences are highly soluble while lacking charges, they are biochemically inert, non-toxic and non-immunogenic, they offer efficient recombinant protein production in a variety of biotechnological host organisms, and they show high stability in blood plasma but are biodegradable by intracellular proteases.

About XL-protein GmbH

XL-protein is a German biotech company commercializing its ground-breaking PASylation® technology, which enables the design of biopharmaceuticals with extended plasma half-life and enhanced action. Based on a strong proprietary technology position, XL-protein focuses at the preclinical as well as clinical development of PASylated proteins in diverse disease areas. XL-protein is engaged in a growing number of partnerships with international pharmaceutical and biotech companies at various levels.

For more information, please visit: www.xl-protein.com

About Antlia Bioscience, Inc.

Antlia Bioscience is a San Diego-based biotech developing groundbreaking peptide-based therapies to treat cardiovascular and metabolic diseases. Using PASylation® and other state-of-the-art techniques, we turn promising peptides into groundbreaking therapies. We are driven to make a profound difference in the treatment of cardiovascular and metabolic diseases and believe that our efforts will result in a paradigm shift in how cardiovascular and metabolic diseases will be treated in the future.

For more information, please visit: antliabio.com

Download full press release

Download full press release

XL-protein and DNX Biopharmaceuticals Announce Collaboration to Develop Novel Inflammasome-Directed Therapeutics using PASylation® Technology

Freising, Germany and San Diego, CA, February 25, 2020 — XL-protein has extended its existing partnership with DNX Biopharmaceuticals, a biopharmaceutical company developing nonimmunogenic, long-acting therapeutic proteins for the treatment of patients with life-long diseases, to develop novel inflammasome-directed therapeutics for the treatment of diseases linked to inflammation, autoinflammation and oncology. DNX has exercised an option for an exclusive license to research, develop and commercialize a novel antagonist from within the DNX portfolio, modified by XL-protein’s PASylation® technology. Financial terms of the collaboration were not disclosed.

The Inflammasome is involved in the initiation and regulation of innate and acquired immunity, sterile inflammation, tissue remodeling, cell death, hypoxia-ischemia and organ failure. Dysfunctional signaling related to the inflammasome complex leads to smoldering or chronic inflammation, which is implicated in a wide range of pathological conditions, including cancer, heart disease, several systemic autoinflammatory conditions such as cryopyrin-associated periodic syndromes (CAPS), type II diabetes, rheumatoid arthritis (RA) and gout.

“We are pleased that DNX has chosen PASylation® technology for the design of biopharmaceuticals with extended plasma half-life and enhanced action,” comments Claus Schalper, CEO of XL-protein, adding that “DNX’s deal with Johnson & Johnson provides another validation of our proprietary platform.”

“We are delighted to be collaborating with XL-protein and the use of their PASylation® technology to progressing DNX’s novel receptor antagonists into clinical development,” said Rajiv Datar, Co-Founder and CEO of DNX.

About PASylation® Technology
‘PASylation’ involves the genetic fusion or chemical conjugation of a therapeutic protein or pharmaceutically active compound with a conformationally disordered polypeptide of defined sequence comprising the small natural amino acids Pro, Ala, and/or Ser. Due to the biophysical size effect, the typically rapid clearance via renal filtration of the original drug can be retarded by a factor 10-100, depending on the length of the PAS chain. PAS sequences are highly soluble while lacking charges, they are biochemically inert, non-toxic and non-immunogenic, they offer efficient recombinant protein production in a variety of biotechnological host organisms, and they show high stability in blood plasma but are biodegradable by intracellular proteases.

About XL-protein GmbH
XL-protein is a German biotech company commercializing its ground-breaking PASylation® technology, which enables the design of biopharmaceuticals with extended plasma half-life and enhanced action. Based on a strong proprietary technology position, XL-protein focuses at the preclinical as well as clinical development of PASylated proteins in diverse disease areas. XLprotein is engaged in a growing number of partnerships with international pharmaceutical and biotech companies at various levels.

For more information, please visit: www.xl-protein.com

About DNX Biopharmaceuticals, Inc.
DNX is a biopharmaceutical company developing long-acting therapeutic proteins for the treatment of patients with life-long diseases. Founded in 2014 and headquartered in San Diego, CA, USA, DNX is pursuing the development of new therapeutic proteins designed to target pathways in the autoinflammation-inflammation spectrum aiming to block key mediators of immunity and inflammation for treating diseases and disorders. DNX is a resident of Johnson and Johnson Innovation – JLABS, Shanghai, a JLABS QuickFire Challenge (QFC) winner and has just closed a deal with the Lung Cancer Initiative at Johnson and Johnson.

For more information, please visit: www.dnxbio.com

Download full press release

Download full press release

Ajinomoto and XL-protein forge Strategic Alliance to develop PASylated therapeutics applying the Corynex® platform

SAN DIEGO, U.S.A., and FREISING, Germany, 18th December, 2018: Ajinomoto Bio-Pharma Services, a fully owned subsidiary of Ajinomoto Co. Inc. (TSE: 2802), and XL-protein GmbH, a privately owned German biopharmaceutical company, are pleased to announce a Strategic Alliance. Ajinomoto will apply its proprietary Corynex® expression system together with XL-protein’s proprietary PASylation® technology for plasma half-life extension to develop a series of therapeutic compounds.

Ajinomoto and XL-protein have established the efficient production of a PASylated proprietary GLP-1 variant with extended half-life at laboratory scale yielding >3 grams soluble protein per liter bacterial culture including facile purification from the supernatant. The PASylated GLP-1 variant maintains high receptor affinity. In vivo pharmacokinetic studies in mice have revealed a drastically prolonged half-life, suggesting potentially weekly or biweekly dosing in human patients. Ajinomoto has started a partnering process for this molecule.

Michiya Kanzaki, Associate General Manager / Business Development of Ajinomoto commented, “We are very happy and excited about this strategic alliance. The alliance combining PASylation® and Corynex® expression technology will provide novel drug candidates with a prolonged half-life and cGMP ready production system with high yield, widening our offerings to the pharmaceutical companies and eventually a meaningful therapeutic option for patients.”

“PASylation® technology is the biological solution for plasma-half extension of therapeutic proteins and peptides. We believe that PASylation® offers a simpler manufacturing process and superior pharmacological properties,” commented Claus Schalper, CEO of XL-protein. “We are excited to work with Ajinomoto as a leading Japanese life science company to further exploit the potential of our technology and to develop new therapeutic options for the treatment of metabolic diseases.”

Financial terms of the agreement have not been disclosed.

Download full press release

Download full press release

Horizon Pharma plc and XL-protein GmbH have entered into a collaboration agreement on a potential next-generation biologic for uncontrolled gout using PASylation® technology

FREISING, January 9, 2018 /XL-protein/ — Horizon Pharma plc (NASDAQ:HZNP) yesterday announced that it has entered into a collaboration agreement with XL-protein GmbH to identify clinical-stage program candidates that could use PASylation® technology to construct a next-generation gout biologic.

PASylation® technology is a biological alternative to synthetic PEGylation and is intended to extend both the half-life of uricase and the duration of treatment for people living with uncontrolled gout, and also has the potential for subcutaneous dosing.

If the agreement yields a clinical-stage candidate, Horizon Pharma will have the right to license the candidate.

About XL-protein GmbH
XL-protein is a German biotech company commercializing its ground-breaking PASylation® technology, which enables the design of biopharmaceuticals with extended plasma half-life and enhanced action. Based on a strong proprietary technology position, XL-protein focuses at the preclinical as well as clinical development of PASylated proteins in diverse disease areas. XL-protein is engaged in a growing number of partnerships with international pharmaceutical and biotech companies at various levels. For more information, please visit www.xl-protein.com

Download full press release

Download full press release

AdAlta and XL-protein execute commercial license agreement

FREISING Germany, 13 November, 2017: XL-protein GmbH is pleased to announce the signing of a commercial agreement with AdAlta Limited (ASX:1AD), the biotechnology company advancing its lead i-body candidate towards clinical development, granting exclusive rights to deploy PASylation® technology for extended activity of AdAlta’s fibrosis therapy, AD-114, in the human body.

XL-protein and the Australian based AdAlta announced an initial agreement on 7 November 2016, at which time AdAlta was granted a research and evaluation license to apply the PASylation technology to its lead anti-fibrotic i-body candidate, AD-114. The agreement announced today is for a commercial license, enabling AdAlta to use XL-protein’s PASylation technology in a commercial setting.

In the period between announcements, AdAlta and XL-protein have successfully developed and evaluated AD-114 in combination with PASylation technology. PASylated AD-114 has demonstrated an extended circulating half-life in the non-human primate studies completed to date and, as a result, increased the therapeutic effect of AD-114. PASylated AD-114 will enable less frequent administration of AD-114 in the clinic, thus making it ideal for treating chronic indications such as Idiopathic Pulmonary Fibrosis (IPF).

AdAlta CEO, Sam Cobb commented, “Addition of the PASylation technology has significantly extended the half-life of our promising anti-fibrotic candidate, AD-114. For patients of chronic diseases, such as IPF, therapies that can be administered less frequently tend to improve patient compliance and quality of life.

Signing a commercial agreement with XL-protein signals our continued progression towards the clinic – we remain on track to commence the first in-human Phase 1 trial for AD-114 in the second half of 2018. This agreement also ensures all commercial infrastructure is in place to support a successful partnering discussion and enable AdAlta to out-license AD-114 to a pharmaceutical partner”.

“PASylation is the emerging platinum standard for plasma-half extension of therapeutic proteins and peptides. We believe that PASylation technology offers a simpler manufacturing process and superior pharmacological properties of the i-body,” commented Claus Schalper, CEO of XL-protein.

We are excited to work with AdAlta to demonstrate the potential of our PASylation technology to develop a new therapeutic option for the treatment of Idiopathic Pulmonary Fibrosis.”

Financial terms of the agreement have not been disclosed.

Download full press release

Download full press release

Jazz Pharmaceuticals and XL-protein GmbH Enter Into a License Agreement on PASylation® Technology to Develop Long-Acting Asparaginase Product Candidates

Freising, July 26, 2017 /XL-protein/ — Jazz Pharmaceuticals plc (Nasdaq: JAZZ) today announced that it has entered into a license agreement with XL-protein GmbH (“XLp”) for the rights to develop, manufacture and commercialize products using XLp’s PASylation® Technology to extend the plasma half-life of selected asparaginase product candidates. Under the terms of the agreement, Jazz will gain access to XLp’s PASylation technology to enable construction of asparaginase molecules intended to extend both the circulating half-life and the duration of therapeutic effect.

Jazz has paid an upfront payment of $2 million and will pay XLp for services and support as specified in the license agreement and for the achievement of certain development, regulatory and commercial milestone events, as well as royalties. Other financial terms are not disclosed.

“We are focused on pursuing development of improved products for patients with acute lymphoblastic leukemia (ALL),” said Russ Cox, executive vice president and chief operating officer of Jazz Pharmaceuticals. “Through our collaboration with XL-protein and our efforts with leaders in expression technology, we are working towards our goal of developing an effective, well-tolerated and long-acting recombinant crisantaspase that could potentially offer a clinically meaningful therapeutic option for patients with ALL.”

“PASylation technology is a biological alternative to PEGylation, the gold standard for plasma half-life extension of therapeutic proteins and peptides up to now. We believe that PASylation technology offers facile manufacturing and traceless metabolisation,” commented Arne Skerra, Cofounder and Chairman of XL-protein. “Historically, asparaginase was one of the first biopharmaceuticals to which PEGylation was applied, and we are excited to work with Jazz Pharmaceuticals to demonstrate the potential of PASylation technology to develop new therapeutic options in acute lymphoblastic leukemia.”

About XL-protein GmbH
XL-protein is a German biotech company commercializing its ground-breaking PASylation® technology, which enables the design of biopharmaceuticals with extended plasma half-life and enhanced action. Based on a strong proprietary technology position, XL-protein focuses at the preclinical as well as clinical development of PASylated proteins in diverse disease areas. XL-protein is engaged in a growing number of partnerships with international pharmaceutical and biotech companies at various levels. For more information, please visit www.xl-protein.com

About Jazz Pharmaceuticals
Jazz Pharmaceuticals plc (Nasdaq: JAZZ) is an international biopharmaceutical company focused on improving patients’ lives by identifying, developing and commercializing meaningful products that address unmet medical needs. The company has a diverse portfolio of products and product candidates, with a focus in the areas of sleep and hematology/ oncology. In these areas, Jazz Pharmaceuticals markets Xyrem® (sodium oxybate) oral solution, Erwinaze® (asparaginase Erwinia chrysanthemi) and Defitelio® (defibrotide sodium) in the U.S. and markets Erwinase® and Defitelio® (defibrotide) in countries outside the U.S. For more information, please visit www.jazzpharmaceuticals.com.

Jazz Pharmaceuticals plc “Safe Harbor” Statement Under the Private Securities Litigation Reform Act of 1995
This press release contains forward-looking statements, including, but not limited to, statements related to the company’s plans to utilize its rights to the XLp’s PASylation technology, the company’s development of improved products for patients with ALL, including the company’s goal of developing an effective, well-tolerated and long-acting recombinant cristantapase and the potential that it that could offer a clinically meaningful improvement for patients with ALL, and other statements that are not historical facts.  These forward-looking statements are based on the company’s current plans, objectives, estimates, expectations and intentions and inherently involve significant risks and uncertainties.  Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties associated with: the company’s ability to achieve the expected benefits (commercial or otherwise) from the acquisition of rights to use XLp’s PASylation technology; pharmaceutical product development and clinical success thereof; the regulatory approval process; and effectively commercializing the company’s products and product candidates; and other risks and uncertainties affecting the company and its development programs, including those described from time to time under the caption “Risk Factors” and elsewhere in Jazz Pharmaceuticals plc’s Securities and Exchange Commission filings and reports (Commission File No. 001-33500), including the company’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2017 and future filings and reports by the company.  Other risks and uncertainties of which the company is not currently aware may also affect the company’s forward-looking statements and may cause actual results and the timing of events to differ materially from those anticipated.  The forward-looking statements herein are made only as of the date hereof or as of the dates indicated in the forward-looking statements, even if they are subsequently made available by the company on its website or otherwise.  The company undertakes no obligation to update or supplement any forward-looking statements to reflect actual results, new information, future events, changes in its expectations or other circumstances that exist after the date as of which the forward-looking statements were made.

Download full press release

Download full press release

AdAlta and XL-protein announce collaboration to develop a long acting version of its lead fibrosis drug candidate AD-114 using PASylation® Technology

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 atwww.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 atwww.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.

Download full press release

Download full press release

Akari Therapeutics Plc and XL-protein GmbH Sign License Agreement to Develop a Long Acting Version of Coversin Using PASylation® Technology

NEW YORK, LONDON, and FREISING, Germany, April 14, 2016 – Akari Therapeutics (NASDAQ: AKTX), an emerging growth, development-stage biopharmaceutical company, and XL-protein, a privately owned biopharmaceutical company, announced today that they have entered into a License, Development and Commercialization Agreement. This partnership is focused on developing a second generation, longer acting version of Coversin.

Under this collaboration agreement, XL-protein will apply its proprietary PASylation® technology for drug half-life extension to Coversin. Coversin is a second-generation complement inhibitor that acts on complement component-C5, preventing release of C5a and formation of C5b-9 (also known as the membrane attack complex or MAC).

XL-protein has previously demonstrated that it can manufacture recombinant PASylated Coversin. An initial study conducted in a mouse model indicates that PASylated Coversin administered by subcutaneous injection remains fully active, with the high C5 binding activity of Coversin retained. In this study, it was found that PASylation of Coversin extended the plasma half-life by over 50 fold.

“XL-protein’s PASylation technology provides an elegant approach to extending the half-life of Coversin, which we hope to demonstrate in future studies will reduce the frequency of dosing,” said Miles Nunn, Chief Scientific Officer of Akari Therapeutics. “Our current plan is to investigate the relative performance of PASylated Coversin, administered by the subcutaneous route, in animal models of disease. If successful, we expect to progress PASylated Coversin to the clinic.””

“We are delighted to enter into the partnership with Akari Therapeutics; the data from the initial study indicate that PASylation could lead to a longer acting, less frequently dosed, subcutaneous version of Coversin”, commented Claus Schalper, Chief Executive Officer of XL-protein. “XL-protein successfully continues to add collaborations with renowned partners that can leverage our best-in-class half-life extension technology.”

Under the terms of the agreement, XL-protein will receive an upfront payment as well as payments for achievement of preclinical, clinical, regulatory and commercial milestones. Furthermore, XL-protein will receive royalties on sales from marketed compounds resulting from the collaboration. Further financial terms have not been disclosed.

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 in various disease areas.  The company is located at Freising, Germany, in the neighbourhoods of Munich International Airport and the Technical University of Munich.

(www.xl-protein.com)

About Akari Therapeutics Plc:
Akari is a clinical-stage biopharmaceutical company focused on the development and commercialization of innovative therapeutics to treat orphan autoimmune and inflammatory diseases. Akari’s lead drug, Coversin is a second-generation complement inhibitor that acts on complement component-C5, preventing release of C5a and formation of C5b-9 (also known as the membrane attack complex or MAC). C5 inhibition is growing in importance in a range of rare autoimmune diseases related to dysregulation of the complement component of the immune system, including Paroxysmal Nocturnal Hemoglobinuria (PNH), atypical Hemolytic Uremic Syndrome (aHUS), and Guillain Barré syndrome (GBS).

(www.akaritx.com)

Download pdf
Download full press release