HDAC6 inhibitors(HDAX)

Novo Holdings and Jeito Capital co-led the $85m round. Credit: Sergey Khakimullin via Getty Images. Belgium-based biotech Augustine Therapeutics has raised €78m ($85m) in funding to support the development of its lead candidate as it enters a Phase I/II trial in Charcot-Marie-Tooth (CMT) disease. Novo Holdings and Jeito Capital co-led the $85m round, with participation from Asabys Partners, Eli Lilly, AdBio partners, V-Bio Ventures, PMV, VIB, Gemma Frisius Fund, the US-based CMT Research Foundation and Newton Biocapital. This follows an initial €17.5m round led by Asabys Partners in July 2024. The new funding will primarily support the clinical advancement of Augustine’s lead candidate, AGT-100216. Augustine’s approach focuses on inhibiting the cytosolic histone deacetylase 6 (HDAC6) enzyme, which plays a key role in neurodegeneration and aging-related cellular processes. The company’s scientific foundation is based on the research of Professor Ludo Van Den Bosch from the VIB-KU Leuven Center for Brain and Disease Research, who identified HDAC6 inhibition as a promising therapeutic strategy for CMT and other neuropathies. AGT-100216 will now enter a Phase I/II proof-of-concept clinical trial for CMT disease, with patient enrolment set to begin later this year. Beyond its lead programme, Augustine will also use the capital to further develop two discovery-stage HDAC6 inhibitors targeting “peripherally restricted and blood-brain barrier-penetrant HDAC6i” for undisclosed neurodegenerative and cardiometabolic conditions. In the announcement accompanying the funding, Augustine Therapeutics’ CEO Gerhard Koenig said: “The therapeutic potential of HDAC6 is widely recognised in our industry, but previous drug approaches have been sub-optimal, particularly for chronic diseases.” Augustine aims to overcome these limitations by using a novel non-hydroxamate, non-hydrazide producing chemotype, designed to enhance efficacy and safety, explained Koenig. Interest in HDAC6 has been growing in the biopharma industry. In November 2023, Novartis expanded into the space with an $80m upfront acquisition of a Phase I asset from Handing Chong Kun Dang Pharmaceutical. Potentially worth up to $1.3bn, the deal granted Novartis exclusive rights to develop and commercialise CKD-510, an investigational HDAC6-inhibiting CMT treatment with orphan drug designation from the US Food and Drug Administration (FDA). CMT is a hereditary neurological disorder caused by genetic mutations that affect the peripheral nerves, leading to muscle weakness and sensory impairment in the hands, arms, legs, and feet. Some mutations damage the nerves directly while others disrupt the protective myelin sheath, both resulting in impaired nerve signal transmission. Beyond CMT, Tenaya Therapeutics’ HDAC6 inhibitor is being evaluated in a Phase I trial in heart failure with preserved ejection fraction.

TORONTO--( BUSINESS WIRE )-- HDAX Therapeutics (“HDAX”), a biotechnology company pioneering a novel approach to targeting HDAC6 for the discovery and development of breakthrough therapeutics for high unmet medical needs, announced the first closing of an oversubscribed US$3.2 (CA$4.3) million seed round. The financing was led by SeedFolio, FACIT, and Toronto Innovation Acceleration Partners (“TIAP”), with participation from Eos Bioinnovation (“Eos”), Ontario Centre of Innovation (“OCI”), and other investors. Proceeds from this financing will support the company’s progress towards preclinical development candidate nomination and further advancement of its pipeline programs. In conjunction with the financing, Brock Reeve, CEO of Eos, and Prakash Gowd, Vice President at TIAP, have joined the HDAX Board of Directors. David Koehler, FACIT and Joe Gatto, SeedFolio will join as Board Observers. Recent advances in HDAC biology have highlighted the critical role of HDAC6 in microtubule dysfunction, validating the therapeutic potential of this target in inflammatory disease, metabolic dysfunction, and neurological disorders. The involvement of HDAC6 in multiple disease states has led to the pursuit of HDAC6-selective drugs by several companies. However, drug development efforts targeting HDAC6 have faced significant challenges, such as poor efficacy, off-target toxicities, and inadequate drug exposure. Drawing on over 7 years of research originating from the lab of renowned serial entrepreneur Professor Patrick Gunning at the University of Toronto, HDAX was purpose-built to address the challenges of developing effective drugs targeting HDAC6. Harnessing its unique molecular recognition technology, HDAX has devised a next-generation binding mechanism that has the potential to discover best-in-class HDAC6 inhibitors. HDAX’s novel mechanism addresses key drug-design challenges of weak binding, poor pharmacokinetics, and off-target toxicities, paving the way for potentially transformative therapeutic benefits for patients. "HDAX Therapeutics is at the forefront of developing next-generation HDAC6-targeting therapeutics to improve patient outcomes. Our novel binding mechanism allows us to effectively and safely target the underlying drivers of disease, positioning us to be potentially best-in-class in the HDAC6 space," said Nabanita Nawar, co-founder and CEO of HDAX. “Securing this financing highlights our truly differentiated innovation and the broad applicability of our technology. With this capital, we are well-positioned to advance our pipeline toward development candidate nomination and ultimately deliver meaningful and safe disease-modifying therapies to patients." “HDAX has made tremendous progress in discovering potent and selective HDAC6 inhibitors, leapfrogging other companies pursuing the target. HDAX’s molecules will not only advance our understanding of HDAC6 biology but also unlock the target’s potential in addressing a number of diseases with high unmet needs,” said Roman Fleck, Executive Chairman of HDAX. Prakash Gowd, TIAP Vice President, commented, “We are incredibly proud to have been able to support HDAX since its inception – first through our University of Toronto Early-Stage (UTEST) program, and now through this pivotal financing. It is a tremendous example of the type of highly innovative and highly promising life sciences ventures we are building in collaboration with our ecosystem partners.” “FACIT commercializes Ontario’s leading oncology ventures, and HDAX’s compelling preclinical profile and strong scientific foundation align with our goals to impact patients,” said David O’Neill, FACIT President. “We look forward to working with the management team and alongside other ecosystem partners to realize the full clinical potential of HDAX’s pipeline.” About HDAX Therapeutics HDAX is a privately held, therapeutics-focused company developing best-in-class HDAC6-targeting therapeutics for neurological and cardiometabolic diseases via a novel mechanism. HDAX is led by a dynamic team with deep expertise in small molecule therapeutics development. To learn more, visit https://hdaxtx.com/ or contact us at info@hdaxtx.com .