Agreements

Date: 2014-11-03

Type of information: Milestone

Compound: ISIS-TTRRx, ISIS-GSK5Rx

Company: Isis Pharmaceuticals (USA - CA) GSK (UK)

Therapeutic area: Rare diseases - Genetic diseases - Infectious diseases - Ophtalmological diseases

Type agreement:

R&D
development
licensing
commercialisation

Action mechanism:

ISIS-TTRRx is an investigational drug that is designed to inhibit the production of all forms of transthyretin and could offer an alternative approach to treat all types of transthyretin-related amyloidosis.

Disease: transthyretin (TTR) amyloidosis

Details:

* On November 5, 2012, Isis Pharmaceuticals and GSK have agreed to amend the clinical development plan and financial terms relating to ISIS-TTRRx to reflect the accelerated development plan for the drug. ISIS-TTRRx is an antisense drug in development with GSK for the treatment of TTR amyloidosis, a severe and rare genetic disease characterized by progressive dysfunction of peripheral nerves and/or heart tissue. The revised development plan anticipates initiation of a Phase 2/3, registration-directed, clinical study later this year.

Financial terms:

In March 2010, GSK and Isis Pharmaceuticals have announced a strategic alliance that will apply the Isis antisense drug discovery platform to seek out and develop new therapeutics against targets for rare and serious disease, including infectious diseases and some conditions causing blindness. Under the terms of the agreement, which covers up to six programs, Isis will receive an upfront $35 million payment from GSK and is eligible to receive on average up to $20 million in milestones per program up to Phase 2 proof-of-concept (PoC). GSK will have the option to license compounds at PoC, and will be responsible for all further development and commercialization. Isis will be eligible to receive license fees and milestone payments, totaling nearly $1.5 billion, in the event all six programs are successfully developed for one or more indications and commercialized through to pre-agreed sales targets. In addition, Isis will receive up to double-digit royalties on sales from any product that is successfully commercialized.
Isis has already received $10 million in milestone payments from GSK related to the development of ISIS-TTRRx. Under the amended terms of the agreement Isis will receive a $2.5 million upfront payment and is eligible to earn a $7.5 million milestone payment upon the initiation of the ISIS-TTRRx Phase 2/3 study. Isis is also eligible to earn an additional $50 million in pre-licensing milestone payments to support the ISIS-TTRRx Phase 2/3 study. In addition, GSK has increased the regulatory and sales milestones payable to Isis should the product achieve registration and meet certain sales thresholds. Isis will also receive double-digit royalties on sales of ISIS-TTRRx.

Latest news:

* On November 3, 2014, Isis Pharmaceuticals announced that it has earned a $5 million milestone payment from GSK related to the designation of ISIS-GSK5Rx as a development candidate. ISIS-GSK5Rx is an antisense drug designed to treat an undisclosed ocular disease.

* On October 9, 2014, Isis Pharmaceuticals announced  that it has earned an $18 million milestone payment from GSK related to the advancement of the Phase 2/3 study of ISIS-TTRRx in patients with familial amyloid polyneuropathy (FAP).

* On July 16, 2014, Isis Pharmaceuticals announced that it has earned a $1 million milestone payment from GSK related to the advancement of the Phase 2/3 study of ISIS-TTRRx in patients with familial amyloid polyneuropathy (FAP). Including this milestone payment, Isis has generated $27 million in upfront and milestone payments for advancing ISIS-TTRRx. This $1 million milestone payment is the fifth of the nearly $58 million in milestone payments Isis is eligible to earn as the Phase 2/3 study progresses. In addition, if GSK elects to exercise its option to exclusively license the ISIS-TTRRxprogram, Isis is eligible to receive a license fee, regulatory and sales milestone payments and double-digit royalties on sales of ISIS-TTRRx.

* On June 24, 2014, Isis Pharmaceuticals announced that it has earned a $1 million milestone payment from GSK related to the advancement of the Phase 2/3 study of ISIS-TTRRx in patients with familial amyloid polyneuropathy (FAP). This $1 million milestone payment is the fourth of the $50 million in milestone payments Isis is eligible to earn as the Phase 2/3 study progresses.

* On May 15, 2014, Isis Pharmaceuticals announced that it has earned a $3.0 million milestone payment from GSK related to the initiation of a natural history study, which will support the advancement of one of the alliance programs. 

* On March 3, 2014, Isis Pharmaceuticals has announced  that it has earned a $1 million milestone payment from GSK related to the initiation of an open-label extension study of ISIS-TTRRx, which is being offered to those patients with familial amyloid polyneuropathy (FAP) who have completed dosing in the Phase 2/3 study of ISIS-TTRRx.  This $1 million milestone payment is the third of the $50 million in milestone payments Isis is eligible to earn as the Phase 2/3 study progresses. 

* On July 30, 2013, Isis Pharmaceuticals has announced that it has earned a $2 million milestone payment from GSK related to the advancement of the ongoing Phase 2/3 study of ISIS-TTRRx in patients with familial amyloid polyneuropathy (FAP). The $2 million milestone payment announced is the first milestone of the $50 million in milestone payments Isis is eligible to earn as the Phase 2/3 study progresses.  In addition, if GSK elects to exercise its option to exclusively license the ISIS-TTRRx program, Isis is eligible to receive a license fee, regulatory and sales milestone payments and double-digit royalties on sales of ISIS-TTRRx.

Is general: Yes