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.

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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.

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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.

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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)

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DNX Biopharmaceuticals and XL-protein Enter into a Shareholder Agreement to Develop and Commercialize Novel Long Acting Biopharmaceuticals.

Irvine, California, and Freising, Germany, February 1, 2016
On June 30, 2015, DNX Biopharmaceuticals (“DNX”) of Irvine, California and XL-protein GmbH (“XLp”) of Freising, Germany, announced they would collaborate in the development and commercialization of novel long acting biopharma-ceutical products with financial terms undisclosed. Under this strategic collaboration, XLp contributes its half-life extension platform technology (PASylation®) and certain molecules that have completed in vivo efficacy proof-of-concept and preclinical studies, and DNX adds its pipeline of candidate molecules for development and commercialization to address a range of unmet needs in Immunology, Metabolism and Ophthalmology.

DNX and XLp now wish to announce that as part of the financial terms, XLp will receive Preferred Shares convertible into common shares for a minority stake in DNX and, as such, have entered into a Shareholder Agreement.

Dr. Rajiv Datar, Chief Executive Officer of DNX, comments: “Given the quality and scope of our collaboration we are very pleased to grant a minority stake to XLp.  DNX was indeed seeking an exciting technology like the PASylation platform to complement our product offering.  Having XLp participate in the equity of the Company provides additional comfort to our joint effort and demonstrates XLp’s commitment.”

Claus Schalper, Chief Executive Officer of XLp, adds: “DNX has assembled an impressive Management Team, Directors and Advisors and we are proud to be part of that alliance.  Furthermore, DNX’s business model is in line with our own business strategy and warrants the quality of our partnership.”

As part of the Agreement, XLp has Board representation and has delegated Mr Schalper to this effect; Prof. Dr. Arne Skerra, Chief Scientific Officer of XLp, will be appointed to the DNX Scientific Advisory Board.

About XL-protein:
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 neighborhoods of Munich International Airport and the Technical University of Munich. (www.xl-protein.com)

About DNX:
DNX is a private biopharmaceutical company developing long-acting therapeutic proteins for the treatment of patients with life-long diseases.  Headquartered in Irvine, CA, USA, DNX is pursuing the development of new therapeutic proteins utilizing 21st century, half-life extension-based drug delivery technologies. (www.dnxbio.com)

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XL-protein and Easton Pharmaceutical sign license agreement to develop biopharmaceuticals using PASylation® technology

Freising, Germany, and Chengdu, P.R. China, December 17, 2015 — XL-protein GmbH and Easton Pharmaceutical Co., Ltd. announced today that they have entered into a License, Development and Commercialization Agreement for novel, long-acting biopharmaceutical products to address a range of unmet needs in ophthalmology and potential further indications. Under this collaboration, XL-protein will apply its proprietary PASylation® technology for drug half-life extension to one Easton target. XL-protein will assume responsibility for early preclinical development activities, Easton will be entitled to further development, manufacturing and marketing of the PASylated compound.

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 tiered, mid- to mid-high single digit royalties on sales from marketed compounds resulting from the collaboration. Easton will have exclusive marketing rights for the P.R. of China for all PASylated products under the agreement. Easton may choose to execute options to obtain world-wide rights and rights for additional therapeutic indications. Further financial terms have not been disclosed.

“We are very pleased to collaborate with XL-protein in Germany and exploit its unique PASylation technology to develop new biological molecules with extended half-life in patients, which will reduce drug administration frequency and the overall therapeutic costs as well”, said Dr. Qing Dong, VP Research & Development of Easton.

“We are excited to collaborate with Easton as one of the leading pharmaceutical companies in the P.R. of China and we are looking forward to a fruitful collaboration on the development of PASylated biopharmaceuticals as important medicines for the treatment of ocular diseases and beyond; this licensing deal further validates XL-protein’s proprietary PASylation technology”, said Prof. Dr. Arne Skerra, CSO & Managing Director of XL-protein.

About Easton Pharmaceutical Co., Ltd.
Easton Pharmaceutical Co., Ltd., was established in 2009 and is headquartered in Chengdu, China. Easton is dedicated to the development, manufacture and distribution of drug substances and finished products. Our production and manufacturing facility includes API synthesis, tablets, capsules, injection solutions and lyophilization lines, which are built in accordance with EU and US GMP standards. We have a well equipped R&D center and QC labs. Our R&D fields comprise drugs for diabetic, cardiovascular, oncology, anesthetic and analgesics. Following our culture of Sunshine, Value, Innovation and Efficiency, Easton Pharma promises to provide high quality pharmaceutical products for our customers.
www.eastonpharma.cn

About XL-protein GmbH
XL-protein is a privately owned biopharmaceutical company based in Freising, Germany, which exploits its proprietary PASylation® technology to develop biologics with extended plasma half-life and enhanced in vivo activity. PASylation is a fully biological technology that can be applied both to approved biopharmaceuticals to yield second generation drugs (‘biobetters’) and to innovative therapeutic proteins, peptides or small molecule drugs, thus allowing less frequent and lower dosing combined with better patient tolerability. XL-protein pursues the preclinical and the clinical development of PASylated biologics in commercially attractive disease areas. Furthermore, XL-protein is engaged in collaborations with the Pharma and Biotech industry and offers licenses.
www.xl-protein.com

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DNX and XL-protein Announce Collaboration to Develop Novel, Long-Acting Biopharmaceutical Products

New Half-Life Extension Platform Technology Will Support the Development and Commercialization of Novel Therapeutic Proteins Addressing Unmet Needs in Immunology, Metabolism and Ophthalmology

Irvine, CA and Freising, Germany, June 30, 2015 — DNX Biopharmaceuticals, Inc. (“DNX”) a company with a team of experienced industry professionals with a long and successful track record of developing and manufacturing biopharmaceutical products, and XL-protein GmbH (“XLp”), a leader in protein engineering and modification technologies, today announced a collaboration for the development and commercialization of novel, long-acting biopharmaceutical products.  Under this strategic collaboration, XLp will contribute its half-life extension platform technology (PASylation®) and certain molecules that have completed in vivo efficacy proof-of-concept and preclinical studies, and DNX will add its pipeline of candidate molecules for development and commercialization to address a range of unmet needs in Immunology, Metabolism and Ophthalmology.  Financial terms have not been disclosed.

Half-life extension is a critical aspect of developing a successful protein pharmaceutical, as not all efficacious payloads have natural half-lives that are amenable to reasonable dosing intervals or regimens.  The novel PASylation platform is designed to offer improved half-life, pharmacokinetics, pharmacodynamics, bioavailability, solubility and overall enhanced patient compliance and safety.  PASylation is a highly tunable technology and offers a paradigm shift in patient care and better compliance in multiple therapeutic areas to improve the quality of life for millions of patients.

“We are pleased to be partnering with XL-protein on the development of new molecules specifically designed to improving the lives of patients, while simultaneously helping to alleviate the clinical burden,” said Dr. Rajiv Datar, Chief Executive of DNX.  “By combining DNX’s 250+ person-years of experience of biologics process development, clinical development and GMP manufacturing expertise with XLp’s revolutionary PASylation platform, we hope to ‘Make Good Drugs Great,’ and to delivering more gain and less pain to patients.”

“Working with DNX to create a range of novel long-acting biopharmaceuticals that will provide benefits to patients and to the healthcare services by reducing clinical burden is exciting and satisfying,” said Claus Schalper, Managing Director of XL-protein.  “Our team shares a common passion with DNX to ‘Making Good Drugs Even Greater’ by contributing our half-life extension / drug delivery technology to support successful product development and commercialization.”

About DNX
DNX is a biopharmaceutical company developing long-acting therapeutic proteins for the treatment of patients with life-long diseases.  Headquartered in Irvine, CA, USA, DNX is pursuing the development of new therapeutic proteins utilizing 21st century, half-life extension-based drug delivery technologies. www.dnxbio.com

About XL-protein
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 neighborhoods of Munich International Airport and the Technical University of Munich.
www.xl-protein.com

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XL-protein Signs Licensing Agreement with MSD Animal Health to Develop Biopharmaceuticals using its PASylation® Technology

FREISING, GERMANY, February 12, 2015XL-protein GmbH, Germany, a privately owned biopharmaceutical company, announced today that they have entered into a license agreement with MSD Animal Health (known as Merck Animal Health in the USA and Canada) to develop PASylated biopharmaceuticals for use in animal health. This license agreement follows a research collaboration between the two companies which began in 2012 and included a feasibility study in target animals.

Under the terms of the agreement, MSD Animal Health acquires worldwide exclusive rights for certain biopharmaceutical drug candidates. In support of the commercialization effort, XL-protein will further optimize the drug candidates against undisclosed MSD Animal Health targets using its proprietary PASylation® platform for plasma half-life extension. This technology has been previously used for human health medications. MSD Animal Health will be responsible for clinical development and commercialization of biopharmaceuticals generated under the collaboration.

“We are delighted to be working with such a renowned partner as MSD Animal Health, who is a leader in the field of veterinary medicine”, said Claus Schalper, CEO&CFO of XL-protein. Prof. Dr. Arne Skerra, CSO of XL-protein, added: “This agreement with MSD Animal Health reflects the significant advantages we have seen for our PASylation® platform over competing technologies for creating biologic drug candidates with extended half-life and enhanced action, especially with regard to tolerance and biodegradability in treated subjects.”

“We strongly believe in the product development synergies between human and animal health and look forward to the opportunities this collaboration will offer to meet the unique challenges in the animal health market,” says Holger Lehmann, Head of Drug Discovery at MSD Animal Health.

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XL-protein and YEDA sign business collaboration agreement to commercialize PASylated interferon superagonist

FREISING, GERMANY & REHOVOT, ISRAEL, October 21, 2014

Yeda Research and Development Company Ltd., the technology transfer arm of the Weizmann Institute of Science, Israel, and XL-protein GmbH, Germany, a privately owned biopharmaceutical company, have signed a business collaboration agreement to commercialize a PASylated interferon superagonist – PAS-YNSα8 – which has been jointly developed by scientists at the Weizmann Institute and XL-protein. Under this agreement, YEDA acquires the worldwide exclusive rights for marketing and out-licensing of this compound.

One of the potential uses of PAS-YNSα8 is for treating inflammatory diseases, in particular of the central nervous system. An example is multiple sclerosis (MS), a devastating chronic, progressive immune disease of the central nervous system that can eventually lead to paralysis. Among the drugs today used to treat MS are those based on interferon-beta (IFN-beta).

Weizmann Institute scientists developed a novel, highly active interferon variant, YNSα8. This modified IFN was engineered to bind much more tightly to the interferon receptors. The result is a very potent molecule, which shows a gene activation profile and biological activities that surpass any naturally existing interferon.

Together with scientists at XL-protein, the activity of PAS-YNSα8 was boosted by extending its half-life in the body using PASylation® technology. PASylation® involves the genetic fusion of the therapeutic protein or peptide with a non-structured, expanded polypeptide made of the small amino acids Pro, Ala and Ser (PAS).

In a study that appeared in the Journal of Biological Chemistry (2014, Vol. 289, No. 42, pp. 29014-29029) and was led by Dr. Daniel Harari and Prof. Gideon Schreiber at the Weizmann Institute, it was found that the in vivo half-life of PAS-YNSα8 was increased 10-fold in comparison to standard interferon. Most importantly, the PASylation® did not interfere with the biological activity of this potent IFN; this has been a common technical problem for other methods of extending drug circulation. In a head-to-head comparison with conventional IFN-beta, this long-living superagonist conferred highly improved protection from disease progression in a mouse model of human multiple sclerosis, despite being injected four times less often than IFN-beta and at one-sixteenth of the dosage.

“We are excited by the pronounced therapeutic effect of our PASylated IFN superagonist, which was not accompanied by any observable immunogenic side effects in mice,” said Prof. Schreiber. “Our studies suggest that this potential drug could be safe and might provide clinical benefit surpassing that of IFN-beta, all this with a significantly reduced number of injections and lower  dosage. We hope it will soon be possible to check the effectiveness of our molecule in clinical trials in humans.”

“The biological potency and bioavailability of this novel IFN-based molecule is remarkable. Improved receptor binding, achieved by advanced protein engineering, in synergy with the half-life extension provided by our PASylation® technology, will result in more effective and less frequent dosing for the benefit of patients,” said Prof. Arne Skerra, CSO of XL-protein and co-author of the study. “We are pleased to forge this business alliance with a renowned partner such as YEDA to commercialize this potent biological drug candidate,” added Claus Schalper, CEO of XL-protein.

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XL-protein announces publication of key scientific data on its PASylation® technology

FREISING, GERMANY, August 30, 2013 – XL-protein GmbH announced today that key scientific data have been published in the journal Protein Engineering, Design & Selection (2013, Vol. 26, No. 8, pp. 489–501, 2013). The Open Access Publication “PASylation: a biological alternative to PEGylation for extending the plasma half-life of pharmaceutically active proteins” is also available for download at XL-protein’s web site (http://www.xl-protein.com/publications.html).

A major limitation of biopharmaceutical proteins is their fast clearance from circulation via kidney filtration which strongly hampers efficacy in human therapy. XL-protein has developed conformationally disordered polypeptide chains with expanded hydrodynamic volume comprising the small residues Pro, Ala and/or Ser (PAS). PAS sequences are hydrophilic, uncharged, genetically encodable amino acid polymers with biophysical properties very similar to poly-ethylene glycol (PEG), whose conjugation to drugs is a well known method for plasma half-life extension.

In contrast, beside chemical coupling PAS polypeptides offer fusion to a therapeutic protein on the genetic level, permitting production of fully active proteins in E. coli and other widely used host organisms (including cell culture secretion) without any in vitro modification steps. Importantly, PAS polypeptides are biodegradable, thus avoiding organ accumulation, while showing stability in serum and lacking toxicity or immunogenicity in animals. The publication describes that PASylation® furnishes typical biologics, such as interferon, growth hormone or antibody Fab fragments, with considerably prolonged circulation in vivo.

This work is complemented by another publication “High-yield production of PASylated human growth hormone (hGH) using secretory E. coli technology” that has appeared in the journal BioProcess International (2013, Vol. 11, No. 4, pp. 30–38) and is also available for download at XL-protein’s web site.

“PASylation® offers unique advantages, that is, surprisingly similar biophysical behavior compared with PEGylation, strong and tunable PK extending effects and conservation of high target-binding activity,” stated Uli Binder, CTO of XL-protein GmbH.

Arne Skerra, CEO of XL-protein GmbH, said: “PASylation® enables the preparation of biologically and/or pharmaceutically functional proteins with prolonged and enhanced in vivo activity, which constitutes a bottleneck in current biological drug development and opens exciting commercial opportunities.”

XL-protein’s proprietary PASylation® technology can be applied both to existing biologics, yielding biobetters, or to innovative therapeutic proteins or peptides, leading to tunable prolonged plasma half-life by a factor 10-100 as demonstrated in numerous animal studies up to now.
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