Date: 2016-04-06
Type of information: R&D agreement
Compound: subtype-selective muscarinic receptor agonists
Company: Allergan (Ireland) Heptares Therapeutics (UK), subsidiary of Sosei Group (Japan)
Therapeutic area: Neurodegenerative diseases - Neurological diseases
Type agreement: R&D collaboration licensing
Action mechanism:
Disease: Alzheimer's disease and other neurological diseases
Details: * On April 6, 2016, Allergan and Heptares Therapeutics announced that Allergan's wholly-owned subsidiary, Allergan Pharmaceuticals International Limited and Heptares have entered into a definitive agreement under which Allergan will license exclusive global rights to a broad portfolio of novel subtype-selective muscarinic receptor agonists in development for the treatment of major neurological disorders, including Alzheimer's disease.
Allergan will be responsible for the development of licensed compounds upon initiation of Phase 2b studies and for subsequent manufacturing and commercialization of the products.
The agreement covers first-in-class selective small molecule agonists targeting muscarinic M1 and M4 receptors in the brain, discovered using Heptares' proprietary StaR® technology platform. Allergan will receive exclusive rights to a broad clinical and preclinical portfolio of M1, M4 and dual M1/M4 agonists, including HTL9936 and HTL18318, selective M1 agonists currently in Phase 1 clinical development. The safety, tolerability and pharmacokinetic profile of HTL9936 were assessed in a recently completed Phase 1 study. The data provide strong evidence of a therapeutic window for the selective M1 agonist mechanism in general, and for progression of HTL9936 and similar molecules as medicines to treat cognitive disorders. HTL9936 exhibited good brain penetration and M1 selectivity with no adverse events typically attributed to the stimulation of M2 and M3 receptors. HTL9936 also exhibited robust and statistically significant changes in brain electrical activity measured using multiple electroencephalography (EEG) biomarkers relevant to cognition. These pro-cognitive effects were seen at low doses and low blood concentrations that were safe and well tolerated.
M1 selective compounds are in development for the potential treatment of symptomatic cognitive deficits in Alzheimer's patients, with the potential upside of better tolerability and a more pronounced effect compared with available treatments. M4 selective compounds may provide a novel approach to treat the neurobehavioral symptoms (psychoses) associated with Alzheimer's disease and related neurological disorders, through a different mechanism of action than available antipsychotics. Combined, dual M1/M4 agonists may be able to treat both cognitive impairment and neurobehavioral symptoms.
Financial terms: Under the terms of the agreement, Heptares will receive an upfront payment of $125 million and is eligible to receive contingent milestone payments of up to approximately $665 million associated with the successful Phase 1, 2 and 3 clinical development and launch of the first three licensed compounds for multiple indications and up to approximately $2.5 billion associated with achieving certain annual sales thresholds during the several years following launch. In addition, Heptares is eligible to receive up to double-digit tiered royalties on net sales of all products resulting from the partnership. Allergan is also committing up to $50 million to a research and development program to be conducted jointly by Allergan and Heptares aimed at advancing multiple candidates through Phase 2 clinical studies.
Latest news: * On May 26, 2016, Sosei announced that the US Federal Trade Commission has granted early termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976 in connection with the global collaboration agreement, executed on 7 April 2016, by Sosei’s subsidiary Heptares Therapeutics Ltd with Allergan’s subsidiary, Allergan Pharmaceuticals International to develop and commercialise a broad portfolio of novel subtype-selective muscarinic receptor agonists for the treatment of major neurological disorders, including Alzheimer’s disease. With completion of the applicable waiting period under the HSR Act, the collaboration agreement with Allergan is effective as of 24 May 2016 under the terms previously announced on 7 April 2016, including the payment to Heptares of a $125 million upfront cash payment.
