Alpine Immune Sciences Announces Presentation Of Preclinical Data Showing Potency Of Its First-Generation Dual ICOS And CD28 Antagonist Vigds In An Animal Model

SEATTLE--(BUSINESS WIRE)--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.

Forward-Looking Statements

This communication contains forward-looking statements (including within the meaning of Section 21E of the United States Securities Exchange Act of 1934, as amended, and Section 27A of the United States Securities Act of 1933, as amended) concerning Nivalis, Alpine (including Alpine’s platform technology, potential therapies, clinical and regulatory objectives and milestone and royalty payment potential), the proposed merger transaction between Nivalis and Alpine and other matters. These statements may discuss goals, intentions and expectations as to future plans, trends, events, results of operations or financial condition, or otherwise, based on current beliefs of the managements of Nivalis and Alpine, as well as assumptions made by, and information currently available to, management of Nivalis and Alpine. Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions, and include words such as “may,” “will,” “should,” “would,” “expect,” “plan,” “believe,” “intend,” “look forward,” and other similar expressions among others. Statements that are not historical facts are forward-looking statements. Forward-looking statements are based on current beliefs and assumptions that are subject to risks and uncertainties and are not guarantees of future performance. Actual results could differ materially from those contained in any forward-looking statement as a result of various factors, including, without limitation, that the conditions to the closing of the merger transaction are not satisfied, that available cash is lower than estimated, that Alpine’s discovery-stage and preclinical program do not advance into the clinic or result in approved products on a timely or cost effective basis or at all. The foregoing review of important factors that could cause actual events to differ from expectations should not be construed as exhaustive and should be read in conjunction with statements that are included herein and elsewhere, including the risk factors included in Nivalis’ registration statement on Form S-4, including the proxy statement/prospectus/information statement therein, Nivalis’ most recent Annual Report on Form 10-K, and Nivalis’ recent Quarterly Report on Form 10-Q and Current Reports on Form 8-K filed with the Securities and Exchange Commission (the “SEC”). Neither Nivalis nor Alpine can give any assurance that the conditions to the merger transaction will be satisfied. Except as required by applicable law, neither Nivalis nor Alpine undertakes any obligation to revise or update any forward-looking statement, or to make any other forward-looking statements, whether as a result of new information, future events or otherwise.

No Offer or Solicitation

This communication is not intended to and does not constitute an offer to sell or the solicitation of an offer to subscribe for or buy or an invitation to purchase or subscribe for any securities or the solicitation of any vote in any jurisdiction pursuant to the proposed transaction or otherwise, nor shall there be any sale, issuance or transfer of securities in any jurisdiction in contravention of applicable law. No offer of securities shall be made except by means of a prospectus meeting the requirements of Section 10 of the United States Securities Act of 1933, as amended. Subject to certain exceptions to be approved by the relevant regulators or certain facts to be ascertained, the public offer will not be made directly or indirectly, in or into any jurisdiction where to do so would constitute a violation of the laws of such jurisdiction, or by use of the mails or by any means or instrumentality (including without limitation, facsimile transmission, telephone and the internet) of interstate or foreign commerce, or any facility of a national securities exchange, of any such jurisdiction.

Additional Information about the Merger and Where to Find It

In connection with the proposed merger, Nivalis has filed a registration statement on Form S-4 with the SEC, including a proxy statement/prospectus/information statement.. The proxy statement/prospectus/information statement and any other relevant documents filed by Nivalis with the SEC may be obtained free of charge through the website maintained by the SEC at www.sec.gov. In addition, investors and stockholders may obtain free copies of the documents filed by Nivalis with the SEC (when they become available) by directing a written request to: Nivalis Therapeutics, Inc., PO Box 18387, Boulder, Colorado 80308, Attention: Investor Relations. Investors and stockholders are urged to read the proxy statement/prospectus/information statement and the other relevant materials before making any voting or investment decision with respect to the proposed merger.

Participants in the Solicitation

Nivalis and Alpine, and each of their respective directors and executive officers and certain of their other members of management and employees, may be deemed to be participants in the solicitation of proxies in connection with the proposed transaction. Information about Nivalis’ directors and executive officers is included in Nivalis’ Annual Report on Form 10-K for the year ended December 31, 2016, filed with the SEC on February 13, 2017, and the proxy statement for Nivalis’ 2017 annual meeting of stockholders, filed with the SEC on April 6, 2017. Additional information regarding these persons and their interests in the transaction is included in the proxy statement/prospectus/information statement referred to above.