Agreements

Date: 2017-09-07

Type of information: Exercise of an option agreement

Compound: NY-ESO SPEAR T-cell therapy program including GSK3377794

Company: Adaptimmune (UK) GSK (UK)

Therapeutic area: Cancer - Oncology

Type agreement: licensing

Action mechanism:

• cell therapy/T cell receptor T cell therapy/gene therapy/immunotherapy product. Using its T-cell receptor (TCR) engineering technology, Adaptimmune has created TCRs which are deployed to target the cancer testis antigen, NY-ESO-1, and other targets. The company’s trials in the NY-ESO-1 programme in multiple myeloma, melanoma, sarcoma and ovarian cancer in the US are generating encouraging results, with European trials set to commence shortly, and it has a pipeline of follow-on programmes.

Disease: synovial sarcoma, myxoid round cell liposarcoma

Details:

• • On June 2, 2014, Adaptimmune, a UK biotechnology company developing TCR engineered T-cells to treat cancer, announced that it has entered into a strategic collaboration and licensing agreement with GSK for the development and commercialisation of its lead clinical cancer program. Under the terms of the agreement, Adaptimmune will co-develop its NY-ESO-1 clinical programme and associated manufacturing optimisation work together with GSK. GSK will have an option on the NY-ESO-1 programme through clinical proof of concept, anticipated during 2016, and, on exercise, will assume full responsibility for the programme. The companies will also co-develop other TCR target programmes and collaborate on further optimization of engineered TCR products. As part of its strategic commitment to the collaboration, Adaptimmune will immediately commence work on further TCR programmes with GSK.

Financial terms:

• • On February 2, 2016, Adaptimmune announced that previous guidance relating to the collaboration disclosed potential cash payments of approximately $350m over the first 7 years from 2014 in relation to NY-ESO and two further programs. Given the changes announced, and the advances made across the collaboration, Adaptimmune is updating and expanding this disclosure. Under the terms of the expanded agreement, the potential development milestones Adaptimmune is eligible to receive solely in relation to the NY-ESO program could amount to approximately $500 million, excluding previously received payments, if GSK exercises its option and successfully develops NY-ESO in more than one indication and more than one Human Leukocyte Antigen (HLA) type. In addition, Adaptimmune would receive tiered sales milestones and, as previously disclosed, mid-single to low double digit royalties on worldwide net sales. GSK has the right to nominate up to four additional targets in due course and Adaptimmune is eligible to receive further significant undisclosed milestone payments in relation to these earlier stage target programs.
• • On June 2, 2014,  Adaptimmune announced that according to the agreed development plan, the deal could yield payments in excess of $350 million over the next seven years, with significant additional development and commercialisation payments becoming due in subsequent years if GSK exercises all its options and milestones continue to be met. In addition, Adaptimmune would also receive tiered royalties ranging from single to double digits on net sales.

Latest news:

• • On September 7, 2017, Adaptimmune announced that GSK has exercised its option under a collaboration and license agreement signed in 2014 to exclusively license the right to research, develop, and commercialize Adaptimmune’s NY-ESO SPEAR T-cell therapy program. Adaptimmune will receive up to £48 million (~$61 million) from GSK over the course of the transition period. This includes development milestones of up to £18 million (~$23 million) and the option payment of £30 million (~$38 million), which also allows GSK to nominate two additional targets following completion of the transition. Successful continuation of development and subsequent commercialization of NY-ESO would trigger additional payments for development milestones, tiered sales milestones, and mid-single to low double-digit royalties on worldwide net sales. This option exercise extends Adaptimmune's cash runway into 2020.
• In June 2017, data presented in an oral presentation at ASCO from the ongoing study of NY-ESO SPEAR T-cells in synovial sarcoma continued to indicate a favorable risk benefit profile in this aggressive and difficult-to-treat solid tumor. Initial anti-tumor activity was observed in all ongoing cohorts, including low expressors of NY-ESO. NY-ESO SPEAR T-cells continued to be well-tolerated with all reported events of cytokine release syndrome resolved (the majority of events were Grade 1 or 2), and there were no reported events of seizure, cerebral edema, or encephalopathy. Survival data was promising with a median predicted overall survival of 120 weeks (~28 months) among the 12 treated patients in Cohort 1; or, 159 weeks (~37 months) for the ten patients in this cohort who received the target dose of one billion cells. In addition, 6 responses were observed in Cohort 1 patients.
• Adaptimmune and GSK will work together over the coming months to ensure a smooth transition of the NY-ESO SPEAR T-cell development program to GSK. After the transition, GSK will assume sponsor responsibility for all NY-ESO-related activities including ongoing data publications regarding this program. Current plans for ongoing and planned clinical studies are summarized below :
• ¤ Adaptimmune will continue enrollment in the ongoing synovial sarcoma pilot study, which will ultimately transition to GSK. GSK will be responsible for continued clinical investigation including initiating the registration study in this indication. Adaptimmune will continue to enroll patients in the ongoing myxoid/round cell liposarcoma study, which will ultimately transition to GSK.
• ¤  Adaptimmune will cease enrollment in the ongoing NSCLC study, whilst GSK develops plans for its own study of NY-ESO SPEAR T-cells in this indication.
• ¤ Adaptimmune will cease enrollment in the ongoing ovarian study, and GSK will assume responsibility for any additional work in this indication.
• ¤ GSK will take on responsibility for the ongoing multiple myeloma combination study with Keytruda® (pembrolizumab).
• • On January 9, 2017, Adaptimmune Therapeutics announced that GSK has nominated a second target, PRAME (preferentially expressed antigen in melanoma), under the strategic collaboration and licensing agreement between the companies. Adaptimmune will be responsible for PRAME preclinical TCR development and delivery of the IND package to GSK. The nomination of a second target meets a milestone set forth in the agreement. GSK retains the right to nominate up to three additional targets, if GSK exercises its option on NY-ESO; however, this excludes targets on which work is already under way, including Adaptimmune’s proprietary MAGE-A10, MAGE-A4 and AFP programs.
• Under the terms of the agreement, the potential development milestones Adaptimmune is eligible to receive solely in relation to the PRAME program could amount to approximately $300 million, if GSK exercises its option and successfully develops this target in more than one indication and more than one Human Leukocyte Antigen (HLA) type. Adaptimmune would also receive tiered sales milestones and mid-single to low double-digit royalties on worldwide net sales.
• • On February 2, 2016, Adaptimmune and GSK announced that the companies have expanded the terms of their strategic collaboration agreement to accelerate Adaptimmune’s lead clinical cancer program, an affinity enhanced T-cell immunotherapy (GSK3377794) targeting NY-ESO-1, toward pivotal trials in synovial sarcoma. Under the terms of the expanded agreement, the companies will accelerate the development of Adaptimmune’s NY-ESO therapy into pivotal studies in synovial sarcoma and will explore development in myxoid round cell liposarcoma. Additionally, the companies may initiate up to eight proof-of-principle studies exploring combinations with other therapies, including checkpoint inhibitors. According to the expanded development plan, the studies will be conducted by Adaptimmune with GSK effectively funding the pivotal studies and sharing the costs of the combination studies via a success based milestone structure. GSK has the right to nominate up to four additional targets in due course and Adaptimmune is eligible to receive further significant undisclosed milestone payments in relation to these earlier stage target programs.
• • On September 1, 2015,  Adaptimmune Therapeutics announced that the first patient has been dosed in its expanded Phase I/II trial of its affinity enhanced T-cell receptor (TCR) therapeutic targeting the NY-ESO-1 cancer antigen in synovial sarcoma patients. Based on encouraging results in the first cohort of 10 patients, presented at the American Association for Cancer Research (AACR) annual meeting in April 2015, the trial is being expanded to encompass an additional 20 patients in two further cohorts. The expansion of Adaptimmune’s trial also triggers two milestone payments from GSK. Adaptimmune is collaborating with GSK for the development of its NY-ESO TCR program through a strategic cancer immunotherapy partnership announced in June 2014. Under the terms of the agreement, GSK has an exclusive option to license Adaptimmune’s NY-ESO TCR therapeutic and upon exercise would assume full responsibility for further development and commercialization of the therapeutic.

Is general: Yes