4BIO Capital Portfolio Company Hornet Therapeutics emerges from stealth with data published in Science demonstrating the first potential drug intervention for Epstein-Barr Virus (EBV) driven disease

• 4BIO Capital incubated company launches with the first ever small molecule drug that has potential for treating EBV-driven diseases

• New data demonstrates decreased EBV latency upon inhibition of the host metabolic enzyme IDO-1 in target cells

• The company emerges from stealth with a strategic partnership with Kyowa Kirin and seed financing by 4BIO Capital

• Hornet to conduct proof-of-concept studies for EBV-driven disease with IDO-1 inhibitor, HTX-201, exclusively in-licensed from Kyowa Kirin

LONDON, 23 May 2024 – 4BIO Capital (“4BIO” or “the Group”), an international venture capital firm unlocking the treatments of the future by investing in advanced therapies and other emerging technologies, today announces that its portfolio company, Hornet Therapeutics (“Hornet”), a biotech company focused on developing treatments to address EBV-driven pathologies, today emerges from stealth with the publication of data in the prestigious journal Science, which reports IDO-1 as a host enzyme hijacked by EBV. These data demonstrate that EBV requires IDO-1 to efficiently establish latent infection and causing downstream pathology.

The study specifically identified IDO-1-driven NAD biosynthesis as a metabolic pathway that EBV exploits to meet the bioenergetic demands of nascent infected B cells. Targeting this pathway with an IDO-1 inhibitor hinders B cell transformation and EBV-driven pathogenesis in vitro and in animal models in vivo. This novel early intervention-approach with IDO-1 inhibition provides a therapeutic strategy to prevent EBV-associated diseases, including lymphomas.

Decades of conventional antiviral development have failed to deliver a small molecule compound capable of effectively and specifically targeting EBV. EBV is a major driver of post-transplantation lymphoproliferative diseases (PTLDs) and responsible for a significant proportion of organ loss in solid organ transplant patients, as well as a widely suspected driver of Multiple Sclerosis (MS). The groundbraking findings reported in Science point at IDO-1 inhibition as a potential treatment mechanism for pathologies related to EBV latency.

The use of Hornet’s proprietary, clinically-validated IDO-1 inhibitor, HTX-201, has already demonstrated significant impact on latency, tumorigenesis, tumour burden, and survival in an experimental mouse model of EBV-driven PTLD.

The Company aims to first develop HTX-201 for the prevention of EBV driven PTLD, where in high-risk solid organ transplant recipients this dangerous complication develops in up to 30% of patients, and the fear of emergence of EBV-driven pathology is ever-present across all transplant populations. By intervening early with HTX-201, Hornet is looking to simplify the management of transplant recipients in the first year post-transplant, when the risk for PTLD and graft loss is highest. With around 80,000 solid organ transplantations in Europe and the US each year, there is a significant unmet need, which Hornet is seeking to address. 1,2

Based on the data now published in Science and with access to the clinically tested drug HTX-201, Hornet is poised to progress into phase 1/2 proof-of-concept clinical trials in solid transplant populations within the next 12-18 months. In the future, the Company intends to also target other conditions where EBV is implicated, such as MS, Infectious Mononucleosis and long-COVID.

Hornet emerges out of stealth with a strategic collaboration and licensing agreement with Kyowa Kirin, enabling Hornet Therapeutics to develop and commercialise HTX-201 (formerly known as KHK2455) in EBV-related diseases.

The Company has an experienced team of experts in antiviral discovery and commercialisation, led by Dr Fraser Gray (formerly Vice President, Infectious Diseases, Worldwide Business Development at GlaxoSmithKline) and Professor Christoph Hess (Professor of Medicine at the University of Basel and Director of Experimental Medicine at the University of Cambridge).

Dmitry Kuzmin, Managing Partner at 4BIO Capital and Chairman at Hornet Therapeutics, said: “The potential for HTX-201 is significant, not only for transplant patients but in multiple areas where EBV is implicated, such as MS and long-COVID. We are pleased to unveil Hornet with the publication of these groundbreaking data and look forward to continuing to work with the Company as it begins proof-of-concept clinical trials in solid organ transplant populations.”

Professor Christoph Hess, founder and Chief Scientific Officer at Hornet Therapeutics added: “In a landmark paper published 60 years ago, Drs. Epstein, Achong and Barr first described EBV – and while we have since built a strong molecular and cellular understanding of the EBV–host interaction, and the propensity of the virus to cause malignancy and promote autoimmunity, we unfortunately still lack an effective and specific treatment for EBV-driven diseases. Our data demonstrate that HTX-201 has the potential to hinder EBV latency in its primary host cells, the B cells. If our findings translate to clinical benefit it would be a huge step forward in this disease area.”

Dr Fraser Gray, Chief Executive Officer at Hornet Therapeutics added: “The ability to intervene early with this small molecule inhibitor in multiple settings, including solid transplant populations, will have a significant impact on many patients affected by EBV. We have an experienced development team actively planning the proof-of-concept clinical trials in transplant patients, where we think HTX-201 can address a clear unmet need.”

1 European Directorate for the Quality of Medicines and Healthcare - Transplant Newsletter - October 2023

2 Organ Procurement and Transplantation Network, US Dept of Health and Human Services - January 2024