Company Plans to File IND in 2018 for First in Class Molecule
SEATTLE, WA, USA I June 14, 2017 I Alpine Immune Sciences, Inc. (Alpine), a biotechnology company developing a next-generation immune modulation platform, today announced results from a preclinical study evaluating first-generation variant Ig domains (vIgDs™) from the company’s lead program, ALPN-101. These vIgDs consisted of an ICOS ligand-based inhibitory domain engineered to acquire CD28 modulatory properties, creating a potential first-in-class dual ICOS/CD28 pathway inhibitor. Results presented demonstrate meaningful activity in an aggressive animal model of graft vs. host disease (GvHD), suggesting that the ALPN-101 program and other Alpine vIgDs could potentially have clinical therapeutic utility in multiple inflammatory diseases. The data will be presented today in a poster session at FOCiS 2017, the annual meeting of the Federation of Clinical Immunology Societies, in Chicago.
“This study demonstrates meaningful activity in an animal model of one of Alpine’s first-generation vIgDs, part of the ALPN-101 development program. This is noteworthy because there are currently no FDA-approved therapies for the treatment of GvHD, and the severity of the disease model suggests that ALPN-101 vIgDs may be useful for other inflammatory conditions as well,” said Stanford Peng, M.D., Ph.D., executive vice president of Research and Development and chief medical officer of Alpine.
Additional preclinical studies are currently underway with Alpine’s second- and third-generation ALPN-101 vIgDs, with results expected to be presented in an upcoming scientific forum.
GvHD currently has no FDA-approved treatment options, and has a major impact on survival following transplantation. Transplant-related mortality is as high as 92 percent in grade IV acute GvHD. Approximately 30 to 50 percent (2,500 – 4,200 per year in the U.S.) of bone marrow transplant patients will develop clinically significant GvHD.
“These preclinical data suggest directed evolution of immuno-modulatory domains via our vIgD platform can provide the basis for novel therapeutics for the treatment of GvHD and other serious inflammatory conditions,” said Mitchell H. Gold, M.D., executive chairman and chief executive officer of Alpine. “With our upcoming merger with Nivalis Therapeutics, we expect to have significant resources to accelerate the development of our platform into other promising areas for both inflammation and oncology applications.”
Preclinical Study Design and Results
The immunoglobulin superfamily (IgSF) is a large, diverse family of proteins expressed on immune cells that play a critical role in regulating the immune system. These proteins have been extensively studied in cancers and autoimmune diseases. Most therapeutic strategies targeting this family of proteins have employed monoclonal antibodies binding to a single receptor on a cell. In contrast, Alpine’s vIgD platform seeks to engineer human IgSF extracellular domains, potentially tailoring their affinity to multiple but specific target ligands.
In the preclinical study presented at FOCiS 2017, Fc fusion proteins incorporating these evolved immunomodulatory IgSF domains were tested in vitro and in vivo. Belatacept, an FDA-approved immunosuppressive T-cell co-stimulation blocker, was used for comparison.
Results showed that in an animal model Alpine’s novel first-generation ICOS/CD28 dual antagonist vIgDs were more potent than belatacept in attenuating T cell activation in vitro as assessed by proliferation and cytokine production. Alpine’s first-generation ICOS/CD28 vIgD molecule also significantly reduced markers of disease activity in an animal model of GvHD as assessed by a standard disease activity score (comprised of overall health and activity, skin and hair changes, and body weight loss).
Alpine’s Planned Merger with Nivalis Therapeutics
In April 2017, Alpine and Nivalis Therapeutics, Inc. (NASDAQ:NVLS) announced that they had entered into a definitive merger agreement under which Alpine will merge with and into a wholly-owned subsidiary of Nivalis in an all-stock transaction with the surviving company named ‘Alpine Immune Sciences, Inc.’ and trading on the NASDAQ under the ticker symbol ‘ALPN’. The merger will result in a combined company with a novel protein-based discovery platform focused on inflammation and immuno-oncology. The merger is expected to close in the third quarter of 2017, subject to the approval of the stockholders of each company and the satisfaction or waiver of other customary conditions.
About Alpine Immune Sciences, Inc.
Alpine Immune Sciences, Inc. was founded in 2015 and is focused on developing novel protein‐based immunotherapies using its proprietary variant immunoglobulin domain (vIgD) platform technology. The vIgD platform is designed to create novel therapeutics that modulate multiple therapeutic targets, including many present in the immune synapse. Alpine’s vIgDs are developed using a unique process known as directed evolution, which can produce proteins capable of either enhancing or diminishing an immune response and thereby may apply therapeutically to both oncology and inflammatory diseases. Alpine has also developed its transmembrane immunomodulatory protein (TIP™) technology, based on the vIgD platform, to enhance engineered cellular therapies. In October 2015, Alpine signed a worldwide research and license agreement with Kite Pharma, Inc. (NASDAQ: KITE) for up to $535 million in upfront and potential milestone payments and, in addition, royalties on resulting sales. The agreement allows Kite access to certain targets developed using Alpine’s TIP platform. For more information visit www.alpineimmunesciences.com/.
About Nivalis Therapeutics, Inc.
Nivalis Therapeutics, Inc. (http://www.nivalis.com) is a pharmaceutical company that has historically been focused on the discovery and development of product candidates for patients with cystic fibrosis, or CF. Nivalis’ development candidates selectively target an enzyme known as S-nitrosoglutathione reductase (GSNOR). GSNOR regulates levels of an endogenous protein known as S-nitrosoglutathione, or GSNO. Depleted levels of GSNO have been associated with CF, asthma, inflammatory bowel diseases and certain cardiovascular diseases. Following recent disappointing results of a Phase 2 clinical trial of its lead product candidate, cavosonstat, in CF, Nivalis determined to not pursue the development of this compound in CF and to wind down its research and development activities while devoting its efforts to investigating and evaluating strategic alternatives.
SOURCE: Alpine Immune Sciences
Post Views: 138
Company Plans to File IND in 2018 for First in Class Molecule
SEATTLE, WA, USA I June 14, 2017 I Alpine Immune Sciences, Inc. (Alpine), a biotechnology company developing a next-generation immune modulation platform, today announced results from a preclinical study evaluating first-generation variant Ig domains (vIgDs™) from the company’s lead program, ALPN-101. These vIgDs consisted of an ICOS ligand-based inhibitory domain engineered to acquire CD28 modulatory properties, creating a potential first-in-class dual ICOS/CD28 pathway inhibitor. Results presented demonstrate meaningful activity in an aggressive animal model of graft vs. host disease (GvHD), suggesting that the ALPN-101 program and other Alpine vIgDs could potentially have clinical therapeutic utility in multiple inflammatory diseases. The data will be presented today in a poster session at FOCiS 2017, the annual meeting of the Federation of Clinical Immunology Societies, in Chicago.
“This study demonstrates meaningful activity in an animal model of one of Alpine’s first-generation vIgDs, part of the ALPN-101 development program. This is noteworthy because there are currently no FDA-approved therapies for the treatment of GvHD, and the severity of the disease model suggests that ALPN-101 vIgDs may be useful for other inflammatory conditions as well,” said Stanford Peng, M.D., Ph.D., executive vice president of Research and Development and chief medical officer of Alpine.
Additional preclinical studies are currently underway with Alpine’s second- and third-generation ALPN-101 vIgDs, with results expected to be presented in an upcoming scientific forum.
GvHD currently has no FDA-approved treatment options, and has a major impact on survival following transplantation. Transplant-related mortality is as high as 92 percent in grade IV acute GvHD. Approximately 30 to 50 percent (2,500 – 4,200 per year in the U.S.) of bone marrow transplant patients will develop clinically significant GvHD.
“These preclinical data suggest directed evolution of immuno-modulatory domains via our vIgD platform can provide the basis for novel therapeutics for the treatment of GvHD and other serious inflammatory conditions,” said Mitchell H. Gold, M.D., executive chairman and chief executive officer of Alpine. “With our upcoming merger with Nivalis Therapeutics, we expect to have significant resources to accelerate the development of our platform into other promising areas for both inflammation and oncology applications.”
Preclinical Study Design and Results
The immunoglobulin superfamily (IgSF) is a large, diverse family of proteins expressed on immune cells that play a critical role in regulating the immune system. These proteins have been extensively studied in cancers and autoimmune diseases. Most therapeutic strategies targeting this family of proteins have employed monoclonal antibodies binding to a single receptor on a cell. In contrast, Alpine’s vIgD platform seeks to engineer human IgSF extracellular domains, potentially tailoring their affinity to multiple but specific target ligands.
In the preclinical study presented at FOCiS 2017, Fc fusion proteins incorporating these evolved immunomodulatory IgSF domains were tested in vitro and in vivo. Belatacept, an FDA-approved immunosuppressive T-cell co-stimulation blocker, was used for comparison.
Results showed that in an animal model Alpine’s novel first-generation ICOS/CD28 dual antagonist vIgDs were more potent than belatacept in attenuating T cell activation in vitro as assessed by proliferation and cytokine production. Alpine’s first-generation ICOS/CD28 vIgD molecule also significantly reduced markers of disease activity in an animal model of GvHD as assessed by a standard disease activity score (comprised of overall health and activity, skin and hair changes, and body weight loss).
Alpine’s Planned Merger with Nivalis Therapeutics
In April 2017, Alpine and Nivalis Therapeutics, Inc. (NASDAQ:NVLS) announced that they had entered into a definitive merger agreement under which Alpine will merge with and into a wholly-owned subsidiary of Nivalis in an all-stock transaction with the surviving company named ‘Alpine Immune Sciences, Inc.’ and trading on the NASDAQ under the ticker symbol ‘ALPN’. The merger will result in a combined company with a novel protein-based discovery platform focused on inflammation and immuno-oncology. The merger is expected to close in the third quarter of 2017, subject to the approval of the stockholders of each company and the satisfaction or waiver of other customary conditions.
About Alpine Immune Sciences, Inc.
Alpine Immune Sciences, Inc. was founded in 2015 and is focused on developing novel protein‐based immunotherapies using its proprietary variant immunoglobulin domain (vIgD) platform technology. The vIgD platform is designed to create novel therapeutics that modulate multiple therapeutic targets, including many present in the immune synapse. Alpine’s vIgDs are developed using a unique process known as directed evolution, which can produce proteins capable of either enhancing or diminishing an immune response and thereby may apply therapeutically to both oncology and inflammatory diseases. Alpine has also developed its transmembrane immunomodulatory protein (TIP™) technology, based on the vIgD platform, to enhance engineered cellular therapies. In October 2015, Alpine signed a worldwide research and license agreement with Kite Pharma, Inc. (NASDAQ: KITE) for up to $535 million in upfront and potential milestone payments and, in addition, royalties on resulting sales. The agreement allows Kite access to certain targets developed using Alpine’s TIP platform. For more information visit www.alpineimmunesciences.com/.
About Nivalis Therapeutics, Inc.
Nivalis Therapeutics, Inc. (http://www.nivalis.com) is a pharmaceutical company that has historically been focused on the discovery and development of product candidates for patients with cystic fibrosis, or CF. Nivalis’ development candidates selectively target an enzyme known as S-nitrosoglutathione reductase (GSNOR). GSNOR regulates levels of an endogenous protein known as S-nitrosoglutathione, or GSNO. Depleted levels of GSNO have been associated with CF, asthma, inflammatory bowel diseases and certain cardiovascular diseases. Following recent disappointing results of a Phase 2 clinical trial of its lead product candidate, cavosonstat, in CF, Nivalis determined to not pursue the development of this compound in CF and to wind down its research and development activities while devoting its efforts to investigating and evaluating strategic alternatives.
SOURCE: Alpine Immune Sciences
Post Views: 138
