ExonHit has developed its own therapeutic pipeline based on its unique gene to drug discovery process. We have clinical-stage programs in Alzheimer's disease and pain and early-stage programs in a variety of indications.
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ExonHit has developed its own therapeutic pipeline based on its unique gene to drug discovery process. Starting in 2010, the Company focuses its internal therapeutic activities on cancer projects to take advantage of shorter development timelines and earlier partnering opportunities than for neurodegenerative diseases. Work in neurodegeneration will continue with partners.
> EHT 0202
EHT 0202
EHT 0202 is a GABAA receptor modulator and a PDE4 inhibitor developed for the treatment of Alzheimer’s disease (AD). EHT 0202 is potentially first in a new class of disease modifying therapies, which stimulate the α-secretase pathway, increasing the production of procognitive and neurotrophic sAPPα fragment of the amyloid precursor protein (APP). Results to date suggest that EHT 0202 is able to reduce Aβ burden by redirecting APP processing towards the α-secretase pathway, which has favorable effects on neuron viability and cognition.
Preclinical studies have shown that:
- EHT 0202 protects cortical neurons against Aβ42 and associated stresses and neuroprotection is associated with sAPPα induction;
- EHT 0202 demonstrates procognitive properties in various preclinical models: age-related memory impairment and scopolamine-induced amnesia;
- chronic oral administrations of EHT 0202 reduce Aβ42 levels in brain and CSF in rat and guinea pigs.
Clinical studies
Phase I studies have demonstrated good tolerability of EHT 0202 in healthy young volunteers. No sedative effects or emesis were observed clinically and no negative alteration of attention or cognition were detected. Furthermore, repeated dosing of aged volunteers (60-75 years old) indicated that overall tolerability of EHT 0202 in elderly individuals was good (10-day repeated administration up to 160 mg twice a day).
Results of a Phase IIa study communicated in September 2009 have shown that EHT 0202 is safe and generally well tolerated in patients. Encouraging signs of cognitive improvement, as measured by ADAS-Cog were seen in EHT 0202 treated patients. It was also observed in some assessments, including ADAS-Cog, that the ApoE4 positive subpopulation (patients with one or two of the ApoE4 alleles in their genes) tends to respond better to EHT 0202 treatment than patients with no ApoE4 allele in their genes. (Press Release)
Discussions are ongoing to find a partner for further development of EHT 0202.
For more information on EHT 0202, see the Literature References and posters.
EHT/AGN 0001, EHT/AGN 0002 and EHT/AGN 0003
EHT/AGN 0001 is the most advance product of ExonHit’s collaboration with Allergan. Phase I studies for EHT/AGN 0001 have been completed and the compound is now being considered for Phase II development in pain indications. The compound is the collaboration’s first New Chemical Entity (NCE) to enter clinical studies, and was originally designed and synthesized by ExonHit’s medicinal chemistry team. It took less than four years to go from target identification to the delivery of a clinical product. It was out licensed as well as EHT/AGN 0002 and its associated back-up compounds by Allergan to Bristol-Myers Squibb in March 2010.
At the beginning of 2010, ExonHit and Allergan announced the inclusion of EHT/AGN 0003, a new lead compounds derived from one of its internal medicinal chemistry programs in the field of opthalmology and neurodegenerative indications.
The Preclinical Portfolio - Oncology : EHT 101 and EHt 107 programs
The current lead of the EHT 107 program demonstrated broad low to sub-nanomolar activity across a panel of more than 70 cancer cell lines and is entering in vivo preclinical testing.
For more information on some of our preclinical programs, see Literature References and posters.