New York, NY – January XX, 2025 – SHY Therapeutics (“SHY”), a privately-held U.S. biotechnology company, today announced its emergence from stealth mode, introducing its approach to developing first-in-class small molecule therapeutics that non-covalently target ATPases and GTPases and modulate their activity. SHY’s portfolio includes its lead candidate, SHY-ONC6, an oral proteasome inhibitor, as well as non-covalent pan-KRas inhibitors and programs targeting bacterial and fungal pathogens. Preclinical studies have demonstrated promising efficacy and tolerability of SHY’s compounds in multiple cancer models.

ATP and GTP fuel critical cellular functions, such as cell growth, differentiation, and homeostasis, mediated in part by ATPases and GTPases. SHY’s drug development strategy leverages the essential roles of ATPases and GTPases by designing small molecules that specifically compete for their interactions with ATP or GTP, respectively, and then modulate their function. SHY has designed its portfolio based on computational analyses of existing chemical libraries and machine learning-generated virtual libraries, proprietary competitive GTP binding assays, and ongoing structural-activity relationship refinements.

“Our approach to modulating ATPases and GTPases will expand the range of viable therapeutic targets within these critical protein classes,” said Yaron Hadari, Ph.D., Co-Founder, Chief Executive Officer, and Chief Scientific Officer of SHY Therapeutics. “By focusing on an entire class of targets rather than individual proteins, SHY’s portfolio provides both the tools to design more precise therapeutics and the ability to identify new, clinically relevant targets within these pathways. This dual capability highlights the versatility of our portfolio and its potential to address a range of diseases with high unmet medical needs.”

“SHY has a focused, collaborative model that allows us to efficiently channel resources into breakthrough therapeutics,” added Michael Schmertzler, Co-founder and Executive Chairman of the SHY Therapeutics Board of Directors. “We believe our unique insights and capabilities position us to deliver significant advances, and we look forward to joining forces with partners who share SHY’s vision to take these discoveries forward for patients in need.”

Lead Candidate Expands Clinical Utility of Validated Pathway

SHY’s lead clinical candidate, SHY-ONC6, is an oral proteasome inhibitor that targets the ubiquitin-proteasome pathway, which is essential for the degradation and recycling of damaged or unneeded proteins and the maintenance of cellular health. Focusing on ATPases in the 19S regulatory particle, SHY-ONC6 introduces a new approach to proteasome inhibition, potentially overcoming the limitations of existing agents that target the proteolytic sites in the 20S core particle.

SHY’s preclinical studies in mouse models with human-tumor-derived cell lines suggest that SHY-ONC6’s novel mechanism of action and small molecule structures may deliver enhanced bioavailability and permeability, broader therapeutic efficacy, and reduced toxicity compared to current 20S proteasome inhibitors that often face challenges such as limited efficacy in treating solid tumors and off-target toxicity. SHY plans to file an Investigational New Drug application with the U.S. Food and Drug Administration for SHY-ONC6 in the second half of 2025, with initial study in a broad range of solid tumors.

Additional First-In-Class Programs: Pan-KRas Inhibitors and Anti-Infectives

SHY is developing a portfolio of molecules that non-covalently inhibit GTP binding to wild type and all mutant forms of Kras, a known member of the Ras superfamily of small GTPases and are mutated in about 30 percent of all human tumors. These molecules have demonstrated the ability to inhibit tumor cell proliferation in both in vitro and in vivo models. SHY plans to designate its next clinical candidate—a first-in-class, non-covalent small molecule pan-KRas inhibitor targeting GTP binding—in the second half of 2025.

In addition, SHY is progressing an early-stage anti-infective program. To date, the company has generated encouraging in vitro efficacy data in a range of bacterial and fungal strains of significant public health concern, with in vivo data anticipated in the first half of 2025.

Visionary Founders and World-Class Advisors Advance Mission

SHY was founded by a team of seasoned leaders, including Yaron Hadari (Ph.D., Co-Founder, Chief Executive Officer, and Chief Scientific Officer), Michael Schmertzler (Co-Founder and Executive Chairman), Dr. Mark Mitchnick (Co-Founder and Director), and Stanley Choy (Co-Founder). Together, they combine expertise in science, business, and clinical development to shape SHY’s vision and strategy.

Supporting SHY’s mission are prominent, accomplished scientific and clinical advisors including Dr. Channing Der (University of North Carolina at Chapel Hill), Dr. Richard Cerione (Cornell University), Dr. Ivan Dikic (Goethe University & Max Planck Institute for Biophysics, Frankfurt, Germany), and Dr. Jerome B. Zeldis former Chief Executive Officer of Celgene Global Health and the Chief Medical Officer of Celgene Corporation (acquired by Bristol Myers Squibb).

About SHY Therapeutics

SHY Therapeutics is a private biotechnology company dedicated to advancing small molecule treatments for serious illnesses, including cancer and infectious diseases. Focused on ATPase and GTPase modulation, SHY is developing impactful, differentiated therapeutic programs from its proprietary pharmacophore and compound portfolio. For more information, visit www.shytherapeutics.com and follow the company on LinkedIn.

Company Contacts:

Yaron Hadari, Co-Founder, Chief Executive Officer and Chief Scientific Officer
SHY Therapeutics
E: yaron.hadari@shytherapeutics.com

Michael Schmertzler, Co-Founder and Executive Chairman

SHY Therapeutics

E: michael.schmertzler@shytherapeutics.com

Media Contact:

Priyanka Shah
Elephant Head Communications, LLC
M: +1-908-447-6134
E: pshah@elephantheadcommunicationsllc.com