Epizyme® has entered into strategic collaborations for several of our therapeutic programs. These collaborations are important elements of our strategy to build a leading, independent biopharmaceutical company. We believe that our collaborations contribute to our ability to rapidly advance our therapeutic product candidates, build our product platform and concurrently progress a wide range of discovery and development programs. Our therapeutic collaborations have provided us with approximately $191 million in non-equity funding. Additionally, our therapeutic collaborations provide us with development co-funding and the potential for significant research, development, regulatory and sales-based milestone payments, as well as royalties or profit sharing on any net product sales. We have retained commercialization or co-commercialization rights in the United States for the programs in our Celgene collaboration, and have global rights outside of Japan in our Eisai collaboration.
In April 2012, we entered into a collaboration and license agreement with Celgene under which we granted Celgene an exclusive license to our DOT1L program outside the United States, including EPZ-5676, the therapeutic candidate now in clinical development. We also granted Celgene the option to license rights outside the United States for other HMT programs, excluding HMT targets covered by our two other existing therapeutic collaborations. We retain 100 percent of United States rights and are eligible to receive royalties on net product sales outside of the United States.
Under the terms of the agreement, we received a $65.0 million upfront payment and $25.0 million from the sale of our series C preferred stock to an affiliate of Celgene. In addition, we earned a $25.0 million milestone payment for achieving proof of concept in the EPZ-5676 clinical program, received $5.8 million of development co-funding, and are eligible to earn up to $135.0 million in additional development and regulatory milestone payments related to DOT1L and up to $165.0 million in option exercise fees and development and regulatory milestone payments related to each additional target as to which Celgene exercises its option during an initial option period ending in July 2015. Celgene has the right to extend the option period until July 2016 by making a significant option extension payment. As to DOT1L and each available target as to which Celgene exercises its option, we are eligible to receive royalties for each target at defined percentages ranging from the mid-single digits to the mid-teens on net product sales outside of the United States subject to reduction in specified circumstances.
In March 2015, we entered into an amended and restated collaboration and license agreement with Eisai, under which we reacquired worldwide rights, excluding Japan, to our EZH2 program, including EPZ-6438. Under the original collaboration and license agreement, we had granted Eisai an exclusive worldwide license to our EZH2 program, including EPZ-6438, while retaining an opt-in right to co-develop, co-commercialize and share profits with Eisai as to licensed products in the United States.
Under the amended and restated collaboration and license agreement, we are responsible for global development, manufacturing and commercialization outside of Japan of EPZ-6438 and any other EZH2 product candidates, with Eisai retaining development and commercialization rights in Japan, as well as a right to elect to manufacture EPZ-6438 and any other EZH2 product candidates in Japan. In connection with the amended and restated agreement, we agreed to pay Eisai an upfront payment of $40.0 million, specified milestone payments based on our development and commercialization of EZH2 products outside of Japan and royalties on net sales of EZH2 products outside of Japan.
In January 2011, we entered into a collaboration and license agreement with GSK to discover, develop and commercialize novel small molecule HMT inhibitors directed to three targets from our product platform.
Under the agreement, we received an upfront payment of $20.0 million. In addition, we have received a $3.0 million payment upon the execution of an agreement amendment, $6.0 million of fixed research funding, $9.5 million in research funding payments and $15.0 million in milestone payments and are eligible to receive up to $620.0 million in additional milestone payments, comprising aggregate research, development and regulatory milestone payments of up to $402.0 million and sales-based milestone payments of up to $218.0 million. In addition, GSK is required to pay us royalties on worldwide net product sales.
Companion Diagnostic Collaborations
In collaboration with established diagnostic companies, we are developing a companion diagnostic to identify patients who have certain EZH2 mutations targeted by our investigational EZH2 inhibitor EPZ-6438.
In December 2012, together with Eisai, we entered into an agreement with Roche Molecular Systems, Inc., to develop and to commercialize a companion diagnostic for use with our EPZ-6438 therapeutic product candidate.