M6P Therapeutics presents promising preclinical data on lysosomal storage disorders at the 18th WORLDSymposium™ 2022 | Nation/World

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ST. LOUIS–(BUSINESS WIRE)–February 11, 2022–

M6P Therapeutic (“M6PT” or “the Company”), a private life sciences company developing next-generation gene and enzyme replacement therapies for lysosomal storage disorders (LSD), announced today the presentation of promising preclinical data at the 18th edition of WORLD Symposium ™, a research conference dedicated to lysosomal storage diseases. In four poster presentations, including two presentations at the Contemporary Forum, M6P Therapeutics researchers reported preclinical efficacy results for LSDs, including Sanfilippo B syndrome, Gaucher disease, and Pompe disease.

“We are excited to showcase our S1S3 co-expression platform technology at WORLD Symposiumsaid Pawel Krysiak, President and CEO of M6PT. “The preclinical data we have presented demonstrates the tremendous promise of targeting the mannose 6-phosphate pathway to enable enhanced biodistribution and tissue uptake in both enzyme replacement and gene therapy modalities and may represent therapeutics for new generation for LSD.”

The following posters were presented at WORLD SymposiumTM:

Poster #70: NAGLU-M6P for potential treatment of Sanfilippo B syndrome

Title:Co-expression of phosphotransferase S1S3 in the production cell line enhances phosphorylation of mannose 6 and cellular uptake of alpha-N-acetylglucosaminidase (Sanfilippo syndrome type B)

Date and time: Monday, February 7, 2022, 3:00-5:00 p.m. PT (6:00-8:00 p.m. ET)

Session: Basic Science Summaries

Presenter (in person): Steven Le from the laboratory of Dr. Patricia Dickson, Division of Genetics and Genomic Medicine, Washington University of St. Louis

Sanfilippo B syndrome is characterized by a defect in the gene providing instructions for the production of the enzyme alpha-N-acetylglucosaminidase (NAGLU), located in lysosomes, resulting in the accumulation of glucosaminoglycans (GAGs).

NAGLU-M6P is an enzyme replacement therapy approach using the co-expression of recombinant human NAGLU and S1S3, a modified GlcNAc-1-phosphotransferase, designed to increase M6P content and enhance subsequent cellular uptake of the enzyme . Binding experiments demonstrated up to 40% higher binding of NAGLU-M6P to the cation-independent mannose 6-phosphate receptor (CI-MPR) compared to NAGLU produced without S1S3.

In Sanfilippo B patient fibroblasts, NAGLU-M6P exhibited robust M6P-dependent uptake into cells and reduction of intracellular heparan sulfate. invivo experiments in a Sanfilippo B mouse model showed a broader distribution of NAGLU enzyme activity in mice given NAGLU-M6P compared to NAGLU.

“These data show the potential utility of recombinant co-expression of NAGLU and S1S3 as an effective enzyme replacement therapy in Sanfilippo B syndrome,” said Dr. Lin Liu, Vice President, Research and Development at M6PT. . “We look forward to the further development of this promising therapeutic approach and hope to validate these preclinical results in patients with Sanfilippo B syndrome.”

Poster #120: S1S3 gene therapy for potential treatment of lysosomal storage diseases

Title:A novel S1S3 phosphotransferase co-expression gene therapy platform for lysosomal storage diseases

Date and time:

Contemporary Forum Discussion (including live moderated Q&A): Thursday, February 10, 2022, 10:30-11:30 a.m. PT (1:30-2:30 p.m. ET) followed by:

Poster session: Thursday, February 10, 2022, 3:00-5:00 p.m. PT (6:00-8:00 p.m. ET)

Session: Contemporary Forum Poster Presentations

Presenter (in person): Dr. Andrew Hedman, M6PT Scientist

LSDs are rare, life-threatening genetic diseases characterized by defects in specific lysosomal enzymes.

M6PT has developed a gene therapy platform using adeno-associated virus 9 (AAV9) vector to deliver S1S3 phosphotransferase (PTase) and recombinant lysosomal enzymes into LSD. This co-expression gene therapy is designed to enhance the M6P content on the enzyme, allowing correct targeting to the lysosome.

The researchers reported the potential utility of this gene therapy platform using various LSD models. In a mouse model of mucolipidosis type II, an LSD with GlcNAc-1-phosphotransferase deficiency, AAV9 expression of S1S3 PTase restored phosphorylation of lysosomal enzymes. Additionally, M6P content was increased in tissues of mice treated with AAV9 vectors co-expressing S1S3 PTase and α-Gal A, an enzyme implicated in Fabry disease, compared to treatment with an AAV9 vector expressing α -Gal A alone.

“We are encouraged by the positive preclinical results from our gene therapy co-expression studies,” Dr. Hedman said. “We believe that an S1S3-based gene therapy platform can enhance the cross-correction of lysosomal enzymes in a variety of LSDs and represents a potential advance in the treatment of these disorders.”

Poster #105: M011 for potential treatment of Gaucher disease

Title:M011: A novel highly phosphorylated β-glucocerebrosidase enzyme with broader tissue biodistribution for the treatment of Gaucher disease

Date and time:

Contemporary Forum Discussion: Thursday, February 10, 2022, 1:00-2:00 p.m. PT (4:00-5:00 p.m. ET), followed by:

Poster session: Thursday, February 10, 2022, 3:00-5:00 p.m. PT (6:00-8:00 p.m. ET)

Session: Contemporary Forum Poster Presentations

Presenter (Virtual): Russell Gotschall, Vice President, Research and Development, M6PT

Gaucher disease is a rare autosomal recessive metabolic disorder in which a deficiency in the enzyme β-glucosidase leads to harmful accumulation of glucosylceramide in tissue macrophages and other cells.

M011 is a novel recombinant human β-glucosidase (rhGCase) enzyme co-expressed with S1S3 PTase that produces rhGCase with high levels of M6P, resulting in high levels of bisphosphoryl glycans and high binding affinity for CI-MPR .

invivo experiments in a Gaucher mouse model showed that M011 reduced liver and spleen glucosylshpingosine and removed bone and muscle substrate more effectively than imiglucerase, the enzyme currently used for enzyme replacement therapy in Gaucher disease . Additionally, M011 showed more efficient cellular uptake and wide tissue distribution.

“The superior efficacy and broad distribution of M011 demonstrates its potential as a viable therapeutic approach for Gaucher disease, including types affecting the central nervous system,” said Gotschall. “We are encouraged by these very promising results and look forward to the further development of M011. »

Poster #106: M021 for potential treatment of Pompe disease

Title:M021: A unique glycosylated and highly phosphorylated acid alpha glucosidase enzyme replacement therapy for the treatment of Pompe disease

Date and time: Thursday, February 10, 2022, 3:00-5:00 p.m. PT (6:00-8:00 p.m. ET)

Session: Contemporary Forum Poster Presentations

Presenter (Virtual): Russell Gotschall, Vice President, Research and Development, M6PT

Pompe disease is a rare inherited metabolic disorder in which a deficiency in the enzyme α-glucosidase (GAA) leads to defective catabolism of lysosomal glycogen.

M021 is a novel recombinant human GAA (rhGAA) enzyme co-expressed with PTase S1S3 that enhances M6P levels, resulting in high levels of bis-phosphoryl glycans, high affinity for CI-MPR and low levels of oligosaccharides neutral.

invivo experiments in GAA-deficient mice showed that M021 significantly reduced accumulated muscle glycogen compared to alglucosidase alfa, the current enzyme replacement therapy for Pompe disease.

“These data demonstrate the potential for continued development of M021 as a next-generation treatment for Pompe disease,” said Gotschall. “We plan to complete efficacy evaluations of M021 in mice and hope to advance this potential therapeutic approach in future clinical studies.”

For more information, registration details and to access livestreamed events, presentations and Q&A sessions, please go to WORLD Symposium. Abstracts will also be made available on the Works section of M6PT Company Website following the presentations.

About the annual WORLD Symposium

The world Symposium ™ is designed for basic, translational and clinical researchers, patient advocacy groups, clinicians and anyone interested in learning about the latest discoveries related to lysosomal storage diseases and the clinical investigation of these advances. For more information on the 18th edition of WORLD Symposium ™, please visit https://worldsymposia.org/.

About M6P Therapeutic

M6P Therapeutics is a private, venture-backed biotechnology company developing the next generation of targeted gene and enzyme replacement therapies for lysosomal storage disorders (LSD). M6P Therapeutics’ proprietary S1S3 co-expression platform has the unique ability to enhance phosphorylation of lysosomal enzymes for enzyme replacement and gene therapies, which improves the biodistribution and cellular uptake of recombinant proteins and corrects cross effective gene therapy product. This can potentially lead to more effective treatments with less therapeutic burden, as well as new therapies for currently untreated diseases. The M6P Therapeutics team, with a proven track record in the development and commercialization of drugs for rare diseases, is dedicated to fulfilling the promise of enzyme replacement and gene therapies by harnessing the power of protein phosphorylation at the using its S1S3 co-expression platform. M6P Therapeutics’ mission is to translate advanced science into cutting-edge therapies that address unmet needs within the LSD community. For more information, please visit: www.m6ptherapeutics.com.

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SOURCE: M6P Therapeutic

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PUBLICATION: 02/11/2022 07:30 / DISK: 02/11/2022 07:32

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