Expanded Collaboration Agreement Intended to Accelerate Development of Anticancer T-cell Immunotherapeutics

Two British biotechnology companies have expanded their strategic collaboration in order to accelerate development of anticancer therapies based on T-cell immunotherapy.

GlaxoSmithKline plc (Brentford, United Kingdom) and Adaptimmune Therapeutics plc (Milton Park, United Kingdom) are expanding their agreement relating to Adaptimmune’s lead clinical cancer program, an affinity enhanced T-cell immunotherapy targeting the NY-ESO-1 antigen as it moves toward pivotal trials on synovial sarcoma, a type of cancer that is most common in the soft tissue near the large joints of the arm and leg but have been documented in most human tissues and organs, including the brain, prostate, and heart.

Among the most rapidly expanding group of tumor antigens (Ags) being studied today are the cancer/testis (C/T) Ags, which are either not expressed or are present at very low levels in normal tissues except the testes and perhaps the placenta. Because the testes are not patrolled by the immune system, expression of C/T Ags in this environment is not harmful. Of the C/TAgs described thus far, NY-ESO-1 is among the most immunogenic with not only well-documented spontaneous and vaccine-induced immunity, but also clinical responses in a substantial percentage of chemo-refractory cancers. NY-ESO-1 mRNA is found in approximately 20% to 40% of tumors including melanoma, prostate, transitional cell bladder, breast, lung, medullary thyroid, squamous head and neck, and cervical carcinoma. Because it is expressed in such a wide variety of tumors, NY-ESO-1 offers a unique opportunity to develop a broad-spectrum tumor-specific cancer vaccine.

Adaptimmune is focused on the use of T-cell therapy to treat cancer. It aims to utilize T-cells to target and destroy cancerous cells by using engineered, increased affinity T- cell receptors (TCRs) as a means of strengthening natural patient T-cell responses and overcoming tolerance to cancer. Specifically, cancerous or virally infected cells will typically present peptides of abnormal cancer proteins on their surface in association with tissue-type HLA (Human Leukocyte Antigen) molecules. Adaptimmune’s technology engineers the natural TCR affinity to cancer protein epitopes on the patient’s cells in order to target and then destroy the cancer cells.

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 GlaxoSmithKline effectively funding the pivotal studies and sharing the costs of the combination studies via a success based milestone structure.

Adaptimmune will be eligible to receive approximately 500 million USD solely in relation to the NY-ESO program, excluding previously received payments, if GlaxoSmithKline exercises its option and successfully develops NY-ESO in more than one indication and more than one 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. GlaxoSmithKline 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.

“We are delighted to broaden our collaboration with GlaxoSmithKline, which is also fully committed to the development of this revolutionary T-cell therapy,” said James Noble, CEO of Adaptimmune. “We believe that our affinity enhanced T-cell programs have the potential to deliver important clinical benefit to cancer patients, and it is therefore essential that we accelerate our efforts to meet their needs. We are working closely with GlaxoSmithKline to expedite development of our affinity enhanced T-cell therapy targeting NY-ESO, and if we succeed in generating pivotal data consistent with that of our ongoing studies, we believe it has the potential to be the first engineered T-cell therapy to reach the market.”

Dr. Axel Hoos, senior vice-president of oncology R&D at GlaxoSmithKline, said, “At GlaxoSmithKline we are progressing a pipeline of immuno-oncology therapies to stimulate antitumor immunity in patients. As we highlighted to investors at our R&D event last year, this Adaptimmune collaboration is a key element of that pipeline and is part of a comprehensive program for cell and gene therapy. With this expanded collaboration, we have the opportunity to accelerate the lead program in synovial sarcoma toward pivotal trials and also to investigate several other tumor types and combine the T-cell therapy with immune-modulating therapies such as checkpoint inhibitors.”

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GlaxoSmithKline plc
Adaptimmune Therapeutics plc