Akari Therapeutics Announces Pre-Clinical Development Progress Toward Potential IND on Long-Acting PAS-Nomacopan for Geographic Atrophy (GA)

NEW YORK and LONDON, Feb. 15, 2023 (GLOBE NEWSWIRE) — Akari Therapeutics, Plc (Nasdaq: AKTX), a late-stage biotechnology company developing advanced therapies for autoimmune and inflammatory diseases, today announced updates on progress in the pre-clinical development program for long-acting PAS-nomacopan as a potential treatment for geographic atrophy (GA) secondary to dry age-related macular degeneration (dAMD).

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Bavarian Research Foundation supports the development of an immunosuppressive PASylated antibody fragment to support cardiac xenotransplantation

Munich, September 28, 2022 – A research consortium composed of XL-protein GmbH, Wacker Chemie AG and Ludwig-Maximilians-Universität München (LMU) will develop a novel long-acting immunosuppressive anti-CD40 antibody for the selective suppression of organ rejection, in particular in the area of cardiac xenotransplantation. The antibody fragment is expected to reduce toxic side effects that occur with current treatments. In the future, the antibody fragment is also expected to be used in the therapy of autoimmune diseases. The project will be partly funded by the Bavarian Research Foundation.

Markus Blume, Bavarian State Minister of Science, handed over the funding agreement to the research consortium today: “This funding by the Bavarian Research Foundation is a perfect example of the truly impressive results that can be achieved in Bavaria as a center of innovation. The excellent collaboration between first‑class university-based researchers and industry makes it possible to perform pioneering scientific work that is clearly focused on specific applications. The basic study conducted by LMU, XL-protein and WACKER on therapy following animal-to-human organ transplants could contribute to finding the answer to the shortage of human donor hearts. I congratulate all those involved on receiving their funding and wish them every success in their project,” said Bavarian State Minister Blume. Prof. Dr. Dr. h. c. Arndt Bode, President of the Bavarian Research Foundation added: “The Foundation is very proud of supporting this outstanding research cooperation between Bavarian industrial partners and academia on a subject extremely relevant to the further development of medical treatment.”

The project, headed by XL-protein, will develop a novel immunosuppressive anti-CD40 antibody fragment for the selective suppression of organ rejection with reduced side effects. “This antibody is particularly promising as an immunosuppressant in cardiac xenotransplantation. Although CD40 blockade is essential for heart xenotransplantation from transgenic pigs, no such clinically approved drug is currently available,” stated Prof. Dr. Eckhard Wolf, Professor of Molecular Animal Breeding and Biotechnology at the LMU. To avoid an undesired agonistic effect of the antibody, a monovalent and long-acting Fab fragment will be developed using XL-protein’s PASylation® technology. “XL-protein’s PASylation® technology offers a superior approach to both extend drug half-life and improve patient safety. We expect that this will lead to an innovative biologic with the potential to become a success story not only in cardiac xenotransplantation but potentially also in conventional organ transplantation or in the therapy of autoimmune diseases,” commented Uli Binder, Managing Director of XL-protein.

WACKER will contribute its expertise in the manufacturing of therapeutic proteins to the project. WACKER’s ESETEC® platform technology is used to produce the antibody fragment and evaluate the manufacturing process. The ESETEC® technology enables controlled secretion of the correctly folded proteins into the culture broth during fermentation. “We are pleased to use our know-how in the field of protein production to contribute to the development of an innovative biologic that is expected to increase the chances of success in organ transplantation and creates new ways of therapy of autoimmune diseases. By continually enhancing our innovative ESETEC® technology, we are able to produce complex proteins in high quality and with high yields. ESETEC® thus helps to reduce the manufacturing costs of novel drugs,” said Dr. Christian Hartel, President & CEO of WACKER.

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 length and sequence comprising the small natural amino acids Pro, Ala, and/or Ser. Due to the biophysical size effect, the typically rapid clearance of the original drug can be retarded by a factor of 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 ESETEC® Technology
ESETEC® is a proprietary WACKER technology with a track record of cost-effective production of proteins and antibody fragments. The expression technology is based on modified E. coli strains, which are designed to secrete the desired pharmaceutical proteins into the culture broth in the correctly folded conformation during fermentation. This process can be aided by additional overexpression of proprietary folding helpers. Thus, with ESETEC®, even complex molecules can be produced in high yields and secreted into the culture medium in an active form.

About XL-protein
XL-protein (www.xl-protein.com) is a German biotech company commercializing its ground-breaking PASylation® technology, which enables the design of biopharmaceuticals with extended half-life – in the plasma or the eye – and enhanced action. Based on a strong proprietary technology position, XL-protein focuses on 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.

About WACKER
Wacker Chemie AG (www.wacker.com) is a global company with state-of-the-art specialty chemical products found in countless everyday items, ranging from cosmetic powders to solar cells. WACKER’s portfolio comprises more than 3,200 products supplied in over 100 countries. The business division WACKER BIOSOLUTIONS supplies customized biotech products such as cyclodextrins, cysteine, polyvinyl acetate solid resins, fine chemicals and biopharmaceuticals. WACKER has a global network of 27 production sites, 23 technical competence centers and 52 sales offices. In 2021, the Group’s 14,400 employees generated global sales of €6.21 billion. Wacker Chemie AG is listed on the Deutsche Boerse Prime Standard and on the MDAX (ISIN: DE000WCH8881).

About Ludwig-Maximilians-Universität München
As one of Europe’s leading research universities, LMU Munich is committed to the highest international standards of excellence in research and teaching. Building on its more than 500-year-tradition of scholarship, LMU covers a broad spectrum of disciplines, ranging from the humanities and cultural studies through law, economics and social studies to medicine and the sciences. 18 percent of LMU’s 50,000 students come from abroad, originating from 130 countries worldwide. The know-how and creativity of LMU’s academics form the foundation of the University’s outstanding research record. This is also reflected in LMU’s designation as a “university of excellence” in the context of the nationwide Excellence Strategy to promote top-level university research.

About Bavarian Research Foundation
The Bavarian Research Foundation was founded in 1990 by the Bavarian state government, in order to boost Bavaria as a site for quality high-tech through efficient and flexible promotion of application-based research. The Research Foundation concentrates on forward-looking projects, the realization of which challenges science and commerce conjointly while assuring close and successful collaboration. Up to now, the Bavarian Research Foundation has granted about €621 million to 1,018 research projects. Bavarian State Minister for Science and Art Markus Blume is a member of the Foundation Council.

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Akari Therapeutics Announces Positive Results from Recent Pre-Clinical Studies of Investigational PASylated® Nomacopan That Support the Potential to Advance Research Toward IND/IMPD for Clinical Trials in Geographic Atrophy

NEW YORK and LONDON, July 28, 2022 (GLOBE NEWSWIRE) — Akari Therapeutics, Plc (Nasdaq: AKTX), a late-stage biotechnology company focused on developing advanced therapies for autoimmune and inflammatory diseases, today announced positive results from recent pre-clinical studies on the tolerability and extended dose interval of long-acting PAS-nomacopan in development for geographic atrophy (GA) in dry age-related macular degeneration (dAMD). The results support the potential for PASylated nomacopan to advance toward the regulatory application(s) that would be required to begin clinical trials.

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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.

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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.

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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

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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.

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Akari Therapeutics Presents New Preclinical Data Highlighting Potential of Long-Acting PASylated Nomacopan to Treat Retinal Diseases, Including Age-Related Macular Degeneration (AMD) and Uveitis

NEW YORK and LONDON, Feb. 25, 2021 (GLOBE NEWSWIRE) — Akari Therapeutics, Plc (Nasdaq: AKTX), a late-stage biopharmaceutical company focused on innovative therapeutics to treat orphan autoimmune and inflammatory diseases where complement (C5) and/or leukotriene (LTB4) systems are implicated, announced today the publication of new data in the journal CELLS. The paper, entitled “Immune-Mediated Retinal Vasculitis in Posterior Uveitis and Experimental Models: The Leukotriene (LT)B4-VEGF Axis,” highlights the importance of the LTB4-VEGF axis in the development of sight-threatening retinal inflammation. In a non-infectious allergic uveitis animal model, PAS-nomacopan reduced VEGF by more than 50% compared to saline control, equivalent to the inhibition caused by an anti-VEGF antibody. In addition, PAS-nomacopan was significantly more effective in reducing retinal inflammation than the anti-VEGF antibody.

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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

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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

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DNX Biopharmaceuticals Announces Collaboration With Lung Cancer Initiative at Johnson & Johnson

San Diego, California–(Newsfile Corp. – February 18, 2020) – DNX Biopharmaceuticals, a biopharmaceutical company developing long-acting therapeutic proteins for the treatment of patients with life-long diseases and a resident of Johnson & Johnson Innovation – JLABS, Shanghai, announced today that it has entered into a strategic collaboration with the Lung Cancer Initiative at Johnson & Johnson*. Under terms of the agreement, the Lung Cancer Initiative has taken an exclusive license to research, develop and commercialize novel molecules from within the DNX portfolio. Financial terms of the collaboration were not disclosed.

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Akari Therapeutics Announces Preclinical Ophthalmic Data Showing Nomacopan Reduces Both Vascular Endothelial Growth Factor (VEGF) and Retinal Inflammation Supporting Nomacopan as a Potential Treatment Option for Back-of-the-Eye Diseases

NEW YORK and LONDON, Jan. 27, 2020 (GLOBE NEWSWIRE) — Akari Therapeutics, Plc (Nasdaq: AKTX), a biopharmaceutical company focused on innovative therapeutics to treat autoimmune and inflammatory diseases where the complement and/or leukotriene systems are implicated, announces new preclinical data indicating that nomacopan significantly reduced both retinal inflammation and intraocular VEGF.

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