Overview

Adaptimmune Therapeutics (ADAP) is a clinical-stage biopharmaceutical company focused on providing novel cell therapies to patients, particularly in solid tumors. The company's comprehensive and proprietary SPEAR (Specific Peptide Enhanced Affinity Receptor) T-cell platform enables it to identify cancer targets, find and genetically engineer T-cell receptors (“TCRs”), and produce therapeutic candidates for administration to patients. Using its affinity engineered TCRs, the company aim to become a fully integrated cell therapy company and to be the first company to have a TCR T-cell approved for a solid tumor indication.

Adaptimmune Therapeutics has four SPEAR T-cells in clinical trials, MAGE-A10, MAGE-A4, AFP and NY-ESO. Phase 1/2 clinical trials are ongoing in patients with various cancer tumor types including urothelial, melanoma, head and neck, ovarian, esophageal, gastric, multiple myeloma, hepatocellular cancers and in synovial sarcoma, myxoid round cell liposarcoma (“MRCLS”) and non small cell lung cancer (“NSCLC”).

The company's MAGE-A10 SPEAR T-cells have shown promising tolerability profiles with no evidence of off-target toxicities observed. In particular as of January 27, 2018, there have been no reports of any severe neurotoxic events similar to CAR-T cell related encephalopathy syndrome (“CRES”). The MAGE-A10 triple tumor study dose escalation to 1 billion transduced cells, which is the dose previously observed to provide responses with its NY-ESO SPEAR T-cell, has been recommended by the Safety Review Committee (“SRC”). In the MAGE-A10 NSCLC study, the SRC has recommended modification of the protocol to permit escalation of the patient dose to 1 billion transduced cells with fludarabine and cyclophosphamide preconditioning in the next treatment cohort. In the MAGE-A4 trial patient enrollment has started in bladder, melanoma, head and neck, ovarian, NSCLC, esophageal and gastric cancers.

The company's NY-ESO SPEAR T-cell has shown promising initial results in clinical trials with a 50% response rate and a median projected overall survival of 120 weeks (~28 months) in Cohort 1 of synovial sarcoma (a solid tumor) and 76% overall response rate at day 100 in multiple myeloma. Adaptimmune Therapeutics has also now seen three partial responses (two confirmed and one to be confirmed) and one stable disease in the first four patients dosed in a second solid tumor indication, MRCLS. The company's NY-ESO SPEAR T-cell therapy has breakthrough therapy designation in the United States and has also received orphan drug designation from the U.S. Food and Drug Administration (“FDA”), and European Commission for the treatment of soft tissue sarcoma. The European Medicines Agency (“EMA”) has also granted PRIME regulatory access for its NY-ESO SPEAR T-cell therapy for the synovial sarcoma indication.

In September 2017, GlaxoSmithKline (“GSK”) exercised its option to obtain an exclusive global license to the NY-ESO SPEAR T-cell program. Upon transition of the NY-ESO program to GSK which is anticipated to occur during 2018, GSK will assume full responsibility for all development, manufacturing and commercialization activities for the NY-ESO SPEAR T-cell including progression of the SPEAR T-cell into further clinical trials.

In January 2018, the company announced that the company had successfully manufactured the first SPEAR T-cells for a patient at its Navy Yard facility in Philadelphia. The company intend to use the facility to manufacture SPEAR T-cells for all three of its wholly owned programs. In addition in January 2018 the company also announced an agreement with Cell and Gene Therapy Catapult for vector production in the U.K., which is intended to ensure vector supply for its ongoing and future clinical studies.

The company's SPEAR T-cell platform is being utilized with the aim of maximizing both patient and disease indication coverage in a number of different ways.

Adaptimmune Therapeutics is using its platform to identify and validate cancer targets for development of SPEAR T-cells in multiple indications. Within a given indication, the frequency of expression of these identified targets may be low, and may not be uniformly expressed in every cell within a tumor. As a result, Adaptimmune Therapeutics is developing multiple SPEAR T-cells to different target antigens within selected disease indications to increase treatment potential for any given disease. For example the NY-ESO-1, MAGE-A4 and MAGE-A10 SPEAR T-cells address targets expressed in NSCLC, melanoma, urothelial (bladder) cancers and head and neck cancers, with each of these indications being addressed by at least two of the SPEAR T-cells.Adaptimmune Therapeutics is also developing SPEAR T-cells directed to targets which are closely related to a specific disease indication. The first of these SPEAR T-cells is its AFP SPEAR T-cell which is directed to hepatocellular cancer. Further targets closely associated with other cancers are also being validated.Finally, Adaptimmune Therapeutics is identifying peptides to different Human Leukocyte Antigen (“HLA”) types ensuring that for any given target, for example NY-ESO, MAGE-A10, MAGE-A4 or AFP, the company can address patient populations with different HLA types.

The company also recognize that further development of its SPEAR T-cells may be assisted by an enhancement in efficacy and durability of response. The company therefore have a number of next generation and combination SPEAR T-cell strategies designed to further develop and engineer its SPEAR T-cells in addition to the initiation of combination therapy approaches, the first of which is with Merck & Co., Inc’s (“Merck”) KEYTRUDA®. In addition to its internal next generation programs, to enable continued innovation and development, the company also have collaborations with third parties intended to promote further next generation solutions. These include its collaboration with Universal Cells, Inc. (“Universal Cells”) and its collaboration with Bellicum Pharmaceutical Inc. (“Bellicum”). With Universal Cells, Adaptimmune Therapeutics is looking to develop affinity engineered donor T cells that are universally applicable to all patients. While these “universal cells” would be specific for a given HLA type and target antigen, they would overcome the current limitation of autologous therapies that need to be manufactured specifically for each patient. The enhanced T-cell technology being developed involves selective engineering of cell surface proteins, without the use of nucleases, to develop universal T-cell products. If successful, this will enable it to treat patient populations with an off-the-shelf product. The company's Bellicum collaboration was announced in December 2016 and under the collaboration, the company will evaluate Bellicum’s GoTCR technology (inducible MyD88/CD40 co-stimulation, or iMC) with its SPEAR T-cells for the potential to create enhanced T-cell therapeutics.

Business Strategy

The company's strategic objective is to be a world leader in discovering, developing and commercializing TCR-based T-cell therapies that transform the clinical outcomes of patients with cancer. Adaptimmune Therapeutics has an ambition to be a fully integrated cell therapy company and to have the first TCR T-cell approved for a solid tumor indication. In order to achieve its objectives, Adaptimmune Therapeutics is focused on the following strategies:

Advance its clinical studies for its MAGE-A10, MAGE-A4 and AFP SPEAR T-cells. Adaptimmune Therapeutics has four SPEAR T-cells with open INDs covering multiple indications, three of these being wholly owned. The company plan to advance these wholly owned SPEAR T-cells further during 2018 with the aim of providing initial tolerability and response data for at least one wholly owned SPEAR T-cell during 2018. Adaptimmune Therapeutics is working with leading cancer centers including through its strategic alliance agreement with MD Anderson to advance its SPEAR T-cells.

Continue to use its SPEAR T-cell platform to generate SPEAR T-cells for cancers where existing therapeutic approaches are limited. The company intend to continue to generate new SPEAR T-cells from its fully integrated technology platform, which enables the systematic identification and validation of suitable target peptides, T-cell cloning, engineering of TCRs and preclinical testing processes.

Continue to understand, further enhance and improve the effectiveness and persistence of its SPEAR T-cell therapies. The company continue to evaluate and work to understand the mechanism of action of its SPEAR T-cells, in particular the best approaches for further enhancing the effectiveness and persistence of its SPEAR T-cells. The company continue to further develop its SPEAR T-cells by exploring the addition of other components in its lentiviral vector, which would be expressed in the SPEAR T-cells alongside the engineered TCR. In addition, Adaptimmune Therapeutics is evaluating the combination of its NY-ESO SPEAR T-cell with Merck’s KEYTRUDA® (pembrolizumab) in patients with multiple myeloma. This combination trial is anticipated to transition to GSK during 2018.

Optimize and expand its process development and manufacturing capabilities to maintain its leadership position in the TCR space. Adaptimmune Therapeutics has now opened its own SPEAR T-cell manufacturing facility at the Navy Yard in Philadelphia, U.S. and have secured vector manufacturing capability within a manufacturing facility operated by the Cell and Gene Therapy Catapult in the U.K. The company will continue to expand its SPEAR T-cell and vector manufacturing capability during 2018. In addition the company continue to optimize the manufacture, supply, associated analytical expertise and quality systems for its SPEAR T-cell therapies to ensure that its manufacturing capability is sufficient for later-stage clinical trials and, potentially, initial commercial supply.

Expand its intellectual property portfolio. The company intend to continue building on its technology platform, comprising intellectual property, proprietary methods and know-how in the field of TCRs and T-cells. These assets form the foundation for its ability not only to strengthen its product pipeline, but also to defend and expand its position as a leader in the field of T-cell therapies.

SPEAR T-cell Therapies

The Immune System and T-cells

The immune system plays an important role in targeting and destroying cancer cells. Specifically, T-cells, which are a type of white blood cell, and their receptors create a natural system that is designed to scan the body for diseased cells. In general, cells process proteins internally and then convert these proteins into peptide fragments which are then presented on the cell surface by a protein complex called the Human Leukocyte Antigen, or HLA. T-cells naturally scan all other cells in the body for the presence of abnormal peptide fragments, such as those generated from infectious agents. Recognition of this peptide-HLA complex takes place through the TCR expressed on the T-cells. Binding of naturally occurring TCRs to cancer targets, however, tends to be very poor because cancer proteins appear very similar to naturally occurring proteins on healthy cells and TCRs that recognize what the body sees as “self-proteins” are eliminated during early human development. Even when TCRs recognize cancer cells expressing novel proteins caused by mutations, elements of the immune system, or the cancer itself often suppress the T-cell response.

Target Identification and Validation

Before developing any engineered T-cell or TCR it is important to identify and validate a suitable target cancer peptide. The target must be expressed primarily only on the cancer cells of interest and with expression in normal non-cancerous tissue only where a risk to the patient would be deemed acceptable. Careful validation and identification of targets is important to ensuring that any engineered TCR is specific to the targeted cancer and does not bind to the same target on non-cancer cells, or that the TCR does not recognize a similar peptide derived from a protein in normal cells. The company's target identification platform is focused on three approaches. First, Adaptimmune Therapeutics is using its platform to validate cancer testis antigens, for example the NY-ESO, MAGE-A4 and MAGE-A10 antigens. Second, Adaptimmune Therapeutics is using its platform to identify non-cancer testis antigens which are closely related to a specific disease indication, for example the AFP antigen which is closely related to hepatocellular cancer. Finally, Adaptimmune Therapeutics is identifying targets to different HLA types ensuring that for any given target, the company can address patient populations with different HLA types.

Affinity Engineering

Following identification of a suitable target peptide, the company identify TCRs that are capable of binding to that target peptide. The company then engineer those identified TCRs to enhance and optimize their ability to target and bind to the cancer peptides, thereby enabling a highly targeted immunotherapy. The optimized TCR then undergoes extensive preclinical safety testing prior to administration to patients. The company's SPEAR T-cell platform technology enables it to develop a pipeline of targets and TCR therapeutic candidates that the company believe may be effective in a variety of cancer types that are unresponsive to currently available and experimental therapies. Adaptimmune Therapeutics has four SPEAR T-cells already in clinical trials (NY-ESO, MAGE-A10, MAGE-A4 and AFP) and a pipeline of SPEAR T-cells in development.

Administration to Patients

The process for treating a patient with an engineered TCR therapeutic candidate involves extracting the patient’s T-cells and then combining the extracted cells with its delivery system containing the gene for its affinity-enhanced TCR, through a process known as transduction. The company's delivery system uses a type of self-inactivating (SIN) virus, known as SIN-lentivirus, to transduce the patient’s T-cells and is referred to as a lentiviral vector. The transduced T-cells are then expanded and infused into the patient. When these T-cells encounter a recognized HLA-peptide complex, they multiply and initiate the destruction of the targeted cancer cells.

The company's Wholly Owned Clinical Product Pipeline

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Adaptimmune Therapeutics has Phase 1 clinical trials ongoing with its wholly-owned MAGE-A10, MAGE-A4 and AFP SPEAR T-cells in a total of eight tumor types including NSCLC, head and neck cancer, ovarian, urothelial, melanoma, esophageal, gastric and liver cancers and as shown in the table above.

MAGE-A10 SPEAR T-cell Therapy

Phase 1 clinical trials are ongoing with its MAGE-A10 SPEAR T-cell in NSCLC, urothelial, melanoma and head and neck cancers in the United States, Canada, the United Kingdom and most recently Spain. Initial safety data from the phase 1 studies has shown no evidence of off-target toxicity and as of January 27, 2018 there have been no reports of severe neurotoxic events similar to CAR-T cell-related encephalopathy syndrome (CRES). Further data from its MAGE-A10 SPEAR T-cell trials is expected to be presented at the American Society of Cancer Oncology (“ASCO”) conference in June 2018.

NSCLC: Approximately 80 to 85 percent of all lung cancers are NSCLC, and smoking is by far the leading risk factor. About 40 percent of all NSCLCs are adenocarcinomas. Squamous cell carcinoma is the second most common in the United States and Europe being 25 to 30 percent of NSCLC. Lung cancer is by far the leading cause of cancer death among both men and women, and it is estimated that one out of four cancer deaths are from lung cancer. Lung cancer mainly occurs in older people, and approximately two out of three people diagnosed with lung cancer are 65 or older, while less than two percent are younger than 45.The initial clinical program in NSCLC is an open label Phase 1 modified 3+3 dose escalating study in patients with advanced stage NSCLC expressing the MAGE-A10 antigen. Patients receive preconditioning with fludarabine and cyclophosphamide. The primary objectives of the study are to assess safety and tolerability of its MAGE-A10 TCR therapeutic candidate in patients. Secondary objectives include the assessment of anti-tumor activity and durability of persistence. Enrollment of patients into this program is challenging, however the Safety Review Committee has now recommended a protocol modification to allow dose escalation to treatment of patients with 1 billion T-cells with fludarabine and cyclophosphamide preconditioning in the next treatment cohort, following the initial 100 million T-cell dose level.3-tumor trial: This is a Phase 1 open-label, modified 3+3 dose escalation study of the MAGE-A10 SPEAR T-cell in HLA-A_0201 and HLA-A_0206 positive patients with inoperable or metastatic urothelial cancer (transitional cell cancer of the bladder, ureter or renal pelvis), melanoma, or squamous cell carcinoma of the head and neck expressing the MAGE-A10 antigen. Patients receive preconditioning with modified fludarabine and cyclophosphamide.Urothelial: Urothelial carcinoma is the most common type of bladder cancer. These cancers mainly start in the urothelial cells that line the inside of the bladder or other parts of the urinary tract. Bladder cancer accounts for approximately five percent of all new cancers in the United States, and is the fourth most common cancer in men. Men are about three to four times more likely to get bladder cancer than women. It was estimated that 79,030 new cases of bladder cancer will be diagnosed (about 60,490 in men and 18,540 in women), and about 16,870 deaths from bladder cancer will occur (about 12,240 in men and 4,630 in women) in the United States in 2017. Bladder cancer occurs mainly in older people, and approximately 9 out of 10 people with this cancer are over the age of 55.Melanoma: Melanoma is a cancer that begins in specific skin cells called melanocytes, and exposure to ultraviolet rays is a major risk factor for most melanomas. It is estimated that approximately 87,110 new melanomas will be diagnosed (about 52,170 in men and 34,940 in women), and about 9,730 people were expected to die of melanoma (about 6,380 men and 3,350 women) in the United States in 2017. The risk of melanoma increases as people age, and the average age at diagnosis is 63 years. However, melanoma is not uncommon among those younger than 30, and it is one of the most common cancers in young adults (especially young women).Head and Neck: Cancers of the head and neck, which include cancers of the oral cavity, larynx, pharynx, salivary glands, and nose/nasal passages, account for approximately three percent of all malignancies in the United States. At least 75 percent of head and neck cancers are caused by tobacco and alcohol use. Infection with cancer-causing types of human papillomavirus (“HPV”) is also a risk factor for some types of head and neck cancers. In recent years, there has been a drop in the incidence of head and neck cancers caused by tobacco and alcohol, and a rise in the incidence of head and neck cancers caused by HPV.

Initial patients in this trial have been treated with 100 million T-cells. The Safety Review Committee has now recommended dose escalation to treatment of patients with the 1 billion cell dose.

MAGE-A4 SPEAR T-cell Therapy

Enrollment in the MAGE-A4 SPEAR T-cell trial in urothelial, melanoma, head and neck, ovarian, NSCLC, esophageal and gastric cancers is ongoing. Patients are initially being treated with an initial target dose of 100 million T-cells (safety dose). Multiple sites in the United States are now active and recruiting and will enroll up to 32 patients. Initial data is anticipated during 2018.

The Phase 1, open-label, modified 3+3 dose escalation study is in HLA*02 positive patients with inoperable locally advanced or metastatic melanoma, and urothelial, head and neck, ovarian, non-small cell lung, esophageal, and gastric cancers expressing the MAGE-A4 target peptides. Patients will receive preconditioning with fludarabine and cyclophosphamide.

AFP SPEAR T-cell Therapy

Adaptimmune Therapeutics has a Phase 1, open label, dose escalation study designed to evaluate the safety and anti-tumor activity of its alpha fetoprotein (“AFP”) therapeutic candidate in hepatocellular carcinoma (“HCC”) ongoing in the United States. The trial is also open in the United Kingdom and Spain. The Phase 1 clinical trial will include a dose escalation and expansion of a tolerable dose to explore initial evidence of anti-tumor activity.

AFP is a target peptide associated with hepatocellular carcinoma. Hepatocellular carcinoma is the most common type of liver cancer in adults. Many patients who develop liver cancer have long-standing cirrhosis (scar tissue formation from liver cell damage), and early detection can be difficult because signs and symptoms often do not appear until later stages. It was estimated that approximately 40,710 new cases of liver cancer will be diagnosed (about 29,200 in men and 11,510 in women) and about 28,920 people will die from this disease (about 19,610 men and 9,310 women) in the United States in 2017.

NY-ESO SPEAR T-cell Therapy (partnered with GSK)

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The NY-ESO SPEAR T-cell is currently in clinical trials in the United States and continues to show a promising tolerability profile in all clinical trials as of September 5, 2017 with no severe neurotoxic events similar to CAR-T cell related encephalopathy syndrome (“CRES”) as at January 27, 2018.

On September 7, 2017, the company announced that GSK had exercised its option under the GSK Collaboration and License Agreement to exclusively license the right to research, develop and commercialize the NY-ESO SPEAR T-cell. Further details on exercise of the option can be found in the Core Alliances and Collaborations section below.

Following exercise of this option by GSK, Adaptimmune Therapeutics is transitioning the NY-ESO SPEAR T-cell program to GSK, with full transition anticipated during 2018.

Synovial Sarcoma:

Soft tissue sarcomas can develop from tissues like fat, muscle, nerves, fibrous tissues, blood vessels, or deep skin tissues. There are approximately 50 types of soft tissue sarcomas, including synovial sarcoma, which is a malignant tumor of the soft tissues arising often around joints. Synovial sarcoma is associated with a characteristic chromosomal translocation, and represents about nine percent of all soft tissue sarcomas. This disease is more common in children and young adults, and typically presents at an age ranging from 15 to 40 years. The majority of patients who develop metastatic soft tissue sarcomas are currently incurable, with 75% to 80% of patients not surviving past two to three years. First line therapy typically involves radiotherapy and chemotherapy, as well as surgical resection where possible. There are limited additional treatment options for unresectable, recurrent and metastatic synovial sarcoma, which is nearly always fatal, and systemic therapy is mainly used to provide palliation and slow disease progression.

There are four cohorts in the Phase 1/2 pilot study:

Cohort 1 (patients with high NY-ESO-1 antigen expression and lymphodepletion with cyclophosphamide and fludarabine) — enrollment in this first cohort is now complete.Cohort 2 (patients with low NY-ESO-1 antigen expression and lymphodepletion with cyclophosphamide and fludarabine) — enrollment continues in this cohort.Cohort 3 (patients with high NY-ESO-1 antigen expression and lymphodepletion with cyclophosphamide alone) — only one confirmed response was observed in evaluable patients treated in cohort 3 and as a result, this cohort has now closed. The data from this cohort 3 suggest that fludarabine may be required as part of the pre-conditioning regimen.Cohort 4 (patients with high NY-ESO-1 antigen expression and lymphodepletion with a modified (lower) dose of cyclophosphamide and fludarabine) — given the lack of response seen in cohort 3, cohort 4 was opened and has now fully enrolled. The company expect to present data comparing cohorts 1 and 4 during the American Society of Clinical Oncology (“ASCO”) conference in June 2018.

As of September 2017, 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. There have been no reports of severe neurotoxicity safety events similar to CAR-T cell-related encephalopathy syndrome (CRES) as of January 27, 2018 . One patient experienced a fatal bone marrow failure which was considered related to study treatment by the investigator in the trial. Internal investigations have not identified a mechanism by which the NY-ESO SPEAR T-cells may have caused this bone marrow failure. 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 greater than one billion cells.

The following diagram illustrates the response seen in one patient with synovial sarcoma in cohort 4 of its synovial sarcoma trial. The red circle indicates one of the two target lesions which was in the patient’s lung prior to treatment, at week 4 after T-cell infusion and up to week 8 after T-cell infusion.

https://www.sec.gov/Archives/edgar/data/1621227/000110465918017694/g277081bgi003.jpg Baseline (cohort 4)

34 yr old female; synovial sarcoma lungPrior therapies doxorubicin, ifosfamide,pazopanib, gemcitabine, 7 surgical resectionsShowing target lesion 1 of 2, 54mm per RECIST(v1.1)

https://www.sec.gov/Archives/edgar/data/1621227/000110465918017694/g277081bgi004.jpg Week 4

Had received 2.8 x 109 transduced T-cellsPartial response at 4 weeks90.7% decrease in target lesion 1, 77% decrease in both target lesions 1 and 2 per RECIST (v1.1)

https://www.sec.gov/Archives/edgar/data/1621227/000110465918017694/g277081bgi005.jpg Week 8

Partial response maintainedTarget lesion 1 not measurable at week 12 due to reduction in size

MRCLS:

Enrollment in this program is continuing in the United States and the program is anticipated to transition to GSK during 2018. This is an open-label pilot study in patients to assess preliminary safety and efficacy in this indication. Initially, ten patients will be enrolled. If further characterization of the treatment is required, up to five additional patients may be enrolled. Eligible patients will be HLA-A_02:01, HLA-A_02:05 and/or HLA-A*02:06 with advanced (metastatic or inoperable) MRCLS whose tumor express NY-ESO-1 (defined as >30% of tumor cells that are 2+ or 3+ by immunohistochemistry). Patients receive preconditioning with fludarabine and cyclophosphamide at the same dose that is being used in cohort 4 of its ongoing synovial sarcoma Phase 1/2 study.

Soft tissue sarcomas can develop from tissues like fat, muscle, nerves, fibrous tissues, blood vessels, or deep skin tissues. There are more than 50 types of soft tissue sarcomas, including MRCLS, which is mostly located in the limbs (most frequently in the thighs). MRCLS is a solid tumor associated with a characteristic chromosomal translocation, and represents about 30 to 35 percent of liposarcomas and 5 to 10 percent of all adult soft tissue sarcomas. MRCLS commonly presents at an age ranging from 35 to 55 years.

The NY-ESO SPEAR T-cell appears to have a promising tolerability profile in MRCLS patients and initial responses have been observed in the first four patients dosed, with three partial responses (two confirmed and one to be confirmed) and one stable disease seen.

Ovarian program:

Enrollment in the ovarian program has ceased. GSK will assume responsibility for any further development for this indication and any long term follow up for patients previously enrolled and treated in the program. To date no objective clinical responses have been reported in patients.

Melanoma program:

Enrollment in the melanoma program has ceased. To date no objective clinical responses have been reported in patients.

Myeloma program:

Multiple myeloma is a cancer formed by malignancies of plasma cells, which are found in the bone marrow and are an important part of the immune system. It is estimated that approximately 30,280 new cases of multiple myeloma will be diagnosed in the United States in 2017 (17,490 in men and 12,790 in women). Multiple myeloma is characterized by several features, including low blood counts, bone and calcium problems, infections, kidney problems, monoclonal gammopathy, and by the proliferation of malignant plasma cells within bone marrow. The risk of multiple myeloma goes up as people age, and less than one percent of cases are diagnosed in people younger than 35. Most people diagnosed with this cancer are at least 65 years of age.

Interim results from a Phase 1/2 clinical trial in multiple myeloma patients were reported in Nature Medicine, published on July 20, 2015. This trial has now closed. 25 patients were treated in the study. As at July 2017, the overall response rate at day 100 was 76% (1 sCR, 1 CR, 8 VGPR and 1PR). Three patients remain disease progression free at 39, 56 and 61 months post T-cell infusion. These results were reported in Blood, 130 (Supplement 1), 845.

Enrollment of patients has now started into a multiple myeloma combination study with Merck’s anti-programmed death-1 (“PD-1”) inhibitor, KEYTRUDA® (pembrolizumab). This trial is anticipated to transition to GSK during 2018. The study is evaluating the safety, pharmacodynamics, and preliminary efficacy of the combination.

NSCLC program:

Enrollment in the NSCLC study has completed and GSK will assume responsibility for any further development for this indication. Any patients already enrolled in the NSCLC study will continue to be treated and followed for safety, efficacy and long term follow up.

The conduct and timing of any pivotal trial or other trials using the NY-ESO SPEAR T-cell will be the responsibility of GSK following exercise of its option over the NY-ESO SPEAR T-cell program and full transition of the program to GSK.

Next Generation Technology and Manufacturing Platform Development

Next Generation Therapeutics

The company believe that there is potential to enhance the potency and durability of its SPEAR T-cells, for instance by adding further active proteins into the lentiviral delivery system. These enhancements are designed to result in next generation SPEAR T-cells for future clinical programs. Adaptimmune Therapeutics has multiple development programs ongoing which are researching different modifications to its SPEAR T-cells. For example, Adaptimmune Therapeutics has an active development program for a ‘dnTGFBRII’ SPEAR T-cell. This next generation SPEAR T-cell is designed to block immune suppression by TGFB in certain tumor microenvironments, thereby enhancing the activity and duration of response seen with its SPEAR T-cells within those environments. Adaptimmune Therapeutics is also considering CD8 constructs where the aim is to promote the antigen spread, anti-tumor memory and tumor inflammation seen with its SPEAR T-cells.

Manufacturing Improvements

The company now have its own SPEAR T-cell manufacturing capability at the Navy Yard in Philadelphia, Pennsylvania. Patient SPEAR T-cell manufacture for its wholly owned assets has started. Control of its own manufacturing process enables to improve and further develop its processes for manufacture of its lentiviral vector and SPEAR T-cells. The company's goal is to achieve a more consistent and efficient manufacturing process and ultimately to reduce the cost of supply.

Adaptimmune Therapeutics has made a number of changes to its current SPEAR T-cell manufacturing process. In particular, Adaptimmune Therapeutics is now streamlining some of the manual steps in the process by simplifying the initial T-cell selection through increased use of the antibody-bound magnetic Dynabeads® CD3/CD28. Adaptimmune Therapeutics has also introduced cryopreservation steps which make the logistics of administering its SPEAR T-cells more flexible for patients and which also facilitate treatment of patients outside the United States. Expansion and harvest of the SPEAR T-cells is now serum-free after initial culture preparation and is being further optimized. Finally, Adaptimmune Therapeutics is also working towards automation of parts of the manufacturing process.

For the vector supply, Adaptimmune Therapeutics is developing and evaluating alternative approaches to increase volume and continuity of supply while at the same time decreasing the cost of the vector supply. Adaptimmune Therapeutics is also collaborating with the Cell and Gene Therapy Catapult for the provision of a module within its manufacturing facility at Stevenage, UK to enable its own manufacturing of vector and further enhance its ability to optimize the vector manufacturing process.

Core Alliances and Collaborations

Adaptimmune Therapeutics has entered into core alliance or collaboration agreements with GSK (collaboration and license agreement), MD Anderson (collaboration designed to expedite the development of T-cell therapies for multiple types of cancer); Merck (clinical trial collaboration agreement for the assessment of its NY-ESO SPEAR T-cell therapy in combination with Merck’s PD-1 inhibitor, KEYTRUDA® (pembrolizumab), in patients with multiple myeloma); Universal Cells (collaboration relating to gene editing and HLA-engineering technology); and Bellicum Pharmaceuticals Inc. (Co-Development and Co-Commercialization Agreement).

GSK Collaboration and License Agreement

The company entered into a strategic collaboration and license agreement with GSK in May 2014 (the “GSK Collaboration and License Agreement”) regarding the development, manufacture and commercialization of TCR therapeutic candidates. The collaboration is for up to five programs, the first being the NY-ESO SPEAR T-cell program and the second the PRAME SPEAR T-cell program.

On September 7, 2017 the company announced that GSK had exercised its exclusive option for the NY-ESO SPEAR T-cell program. As part of the option exercise a transition plan was agreed between it and GSK for the transition of the NY-ESO SPEAR T-cell clinical trials and program to GSK. Transition is expected to occur during 2018. Following transition of the program to GSK, GSK will assume full responsibility for the NY-ESO SPEAR T-cell program including any ongoing clinical trials. As a result of the option exercise, the company 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 an 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.

In relation to the second target nominated, Adaptimmune will be responsible for taking the PRAME SPEAR T-cell program through preclinical testing and up to Investigational New Drug (“IND”) application filing. GSK is responsible for the IND filing itself. GSK has an exclusive option over the program. Under the terms of the GSK Collaboration and License Agreement, the potential development milestones eligible related 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 HLA type. Adaptimmune would also receive tiered sales milestones and mid-single to low double-digit royalties on worldwide net sales.

Three other targets may be nominated by GSK at specified times under the GSK Collaboration and License Agreement, excluding any research programs already in progress by Adaptimmune. Upon nomination by GSK of any of these three additional targets, the company will grant to GSK an exclusive option on each target, which can be exercised up to four months after approval of an IND application in relation to a TCR therapeutic candidate directed against the nominated target. Nomination also triggers the start of a collaboration program to develop the relevant TCR therapeutic candidate directed to the nominated target peptide.

Following exercise of any option (including the options for the NY-ESO SPEAR T-cell and PRAME SPEAR T-cell programs), the company will grant to GSK an exclusive worldwide license under intellectual property rights specific to the SPEAR T-cell developed under the relevant collaboration programs. GSK will, at its own expense, be fully responsible for all further development and commercialization of the relevant T-cell candidates. The licenses do not include a right for GSK to develop alternative affinity-enhanced TCRs using its intellectual property rights or to develop other TCR therapeutic candidates directed to different target peptides. Under the agreement, Adaptimmune Therapeutics is also prohibited from independently developing or commercializing T-cell therapeutics directed at the targets subject to outstanding options granted to GSK.

Under the GSK Collaboration and License Agreement, the company received an upfront payment of $42.1 million in June 2014 and are entitled to various milestone payments based on the achievement of specified development and commercialization milestones. As of December 31, 2017, the company had achieved development milestones of $49.3 million.

In addition to the development milestones, Adaptimmune Therapeutics is entitled to royalties from GSK on all GSK sales of SPEAR T-cells licensed under the agreement, varying between a mid-single-digit percentage and a low-double-digit percentage of net sales, subject to certain agreed reductions, dependent on the cumulative annual net sales for each calendar year. Royalties are payable while there is a jointly owned or solely owned valid patent claim covering the SPEAR T-cell in the country in which the relevant SPEAR T-cell is being sold and, in each case, for a minimum of 10 years from first commercial sale of the relevant TCR therapeutic. Sales milestones also apply once any TCR therapeutic covered by the GSK Collaboration and License Agreement is on the market.

The GSK Collaboration and License Agreement is effective until all payment obligations expire, including any ongoing royalty payments due in relation to GSK’s sale of any covered TCR therapeutic candidates. The agreement can also be terminated on a collaboration program-by-collaboration program basis by GSK for lack of feasibility or inability to meet certain agreed requirements. Both parties have rights to terminate the agreement for material breach upon 60 days’ written notice or immediately upon insolvency of the other party. GSK has additional rights to terminate either the agreement or any specific license or collaboration program upon 60 days’ written notice to it. Additional payments may be due to it as a result of such termination, and where the company continue any development of any TCR therapeutic candidate resulting from a terminated collaboration program, depending on the stage of development, royalties may be payable to GSK at a mid-single-digit percentage rate of net sales. The company also have rights to terminate any license where GSK ceases development or withdraws any licensed SPEAR T-cells in specified circumstances.

Details of the relationship are also set out in “Risk Factors — Risks Related to The company's Reliance Upon Third Parties — The company rely heavily on GSK for its NY-ESO TCR therapeutic candidate clinical program, which may also affect other SPEAR T-cell programs”.

Intellectual Property

The company actively seek to protect the intellectual property and proprietary technology that the company believe is important to its business, including seeking, maintaining, enforcing and defending patent rights for its SPEAR T-cells and processes, whether developed internally or licensed from third parties. The company's success will depend on its ability to obtain and maintain patent and other protection including data/market exclusivity for its SPEAR T-cells and SPEAR platform technology, preserve the confidentiality of its know-how and operate without infringing the valid and enforceable patents and proprietary rights of third parties. See “Risk Factors—Risks Related to The company's Intellectual Property.”

The company's policy is to seek to protect its proprietary position generally by filing an initial priority filing at the U.K. Intellectual Property Office (“UKIPO”) and/or the U.S. Patent Trademark Office (“USPTO”). This is followed by the filing of a patent application under the Patent Co-operation Treaty claiming priority from the initial application(s) and then application for patent grant in, for example, the United States, Europe (including major European territories), Japan, Australia, New Zealand, India and Canada. In each case, the company determine the strategy and territories required after discussion with its patent professionals to ensure that the company obtain relevant coverage in territories that are commercially important to it and its SPEAR T-cells or TCRs. The company will additionally rely on data exclusivity, market exclusivity and patent term extensions when available, including as relevant exclusivity through orphan or pediatric drug designation. The company also rely on trade secrets and know-how relating to its underlying platform technology, manufacturing processes and SPEAR T-cells.

As of December 31, 2017 the company owned or jointly owned approximately 150 granted patents (of which 15 are U.S.-issued patents) and 107 pending patent applications (of which 7 are U.S. National patent applications). These patents and patent applications include claims directed to its SPEAR T-cells, its platform technology used to identify and generate engineered TCR therapeutic candidates, its next generation SPEAR T-cell technology and its manufacturing and process technology.

Product Patents

NY-ESO - The company own granted patents covering the composition of matter of its NY-ESO SPEAR T-cell. The patent claims are directed to the NY-ESO SPEAR TCR and in particular the amino acid substitutions required for such engineered TCR therapeutic candidate. The patent has been granted in major territories including Australia, Europe (Switzerland, Germany, Denmark, France, United Kingdom, Ireland and the Netherlands), New Zealand, Japan and the United States. These granted patents are expected to expire in May 2025.

MAGE-A10 - The company own patent applications covering the composition of matter of its MAGE-A10 TCR therapeutic candidate. The patent application claims are directed to the engineered TCR therapeutic candidate and in particular the amino acid substitutions required for such engineered TCR therapeutic candidate. An initial priority patent application was filed in the UKIPO and a patent application under the applicable Patent Co-operation Treaty has since been filed claiming priority from that U.K. patent application. National applications have been filed in all commercially relevant territories.

AFP - The company own patent applications covering the composition of matter of its AFP therapeutic candidate. As with its NY-ESO and MAGE-A10 TCR therapeutic candidates, the patent application claims are directed to the engineered TCR therapeutic candidate and in particular the amino acid substitutions required for such engineered TCR therapeutic candidate. An initial priority patent application was filed in the UKIPO and a patent application under the applicable Patent Co-operation Treaty has since been filed claiming priority from that U.K. patent application. National applications have been filed in all commercially relevant territories.

MAGE-A4 - The company own three patent applications covering the composition of matter of its MAGE-A4 therapeutic candidate and other related TCRs. As with its NY-ESO and MAGE-A10 TCR therapeutic candidates, the patent application claims are directed to the engineered TCR therapeutic candidate and in particular the amino acid substitutions required for such engineered TCR therapeutic candidate. The initial priority patent applications were filed in the UKIPO and patent applications under the applicable Patent Co-operation Treaty have since been filed claiming priority from that U.K. patent application.

Platform Technology

The company jointly own a number of platform technology patents and patent applications. These are jointly owned with Immunocore Limited (“Immunocore”), a company with whom Adaptimmune Therapeutics has historically had a shared development history, and are directed to certain aspects of the process that the company use to engineer its SPEAR TCRs. For example, patents directed to the di-sulphide bond stabilization technique required to solubilize TCRs for isolation, characterization and validation have been issued in major territories including Australia, Canada, China, major European territories (including the United Kingdom, France, Germany, Spain and Italy), India, Hong Kong, Japan, the United States and South Africa and are expected to expire beginning in 2022. Patents have also been granted in relation to its phage display approach for TCRs and are expected to expire beginning in 2023. The priority patent application was filed in 2002 and patents are now granted in the United States, Australia, Canada, China, major European territories (including the United Kingdom, France, Germany, Spain and Italy), Japan, South Africa, India, Norway and New Zealand. Other examples include an issued patent directed to a method for increasing the affinity of given TCRs to a target peptide (expected to expire in 2025) and patent applications directed to decreasing off-target reactivity and selection for the affinity-enhanced TCRs.

For further information on Immunocore, see further “Related “Risk Factors—Risks Related to The company's Reliance Upon Third Parties—Adaptimmune Therapeutics has a shared development history with Immunocore and as a result jointly-own certainly intellectual property rights which are required for its ongoing business.”

Novel targets

Adaptimmune Therapeutics has filed 29 patent applications under the Patent Cooperation Treaty which cover peptides expressed on the tumor cell surface and the TCRs which recognize them. The applications as filed cover 872 peptides from 63 different target proteins.

TCR libraries

Adaptimmune Therapeutics has filed 10 patent applications which cover large libraries of TCR genes which Adaptimmune Therapeutics has generated and the method of their generation: these act as proprietary sources for screening for TCRs which are the starting points for affinity engineering into clinical candidates.

Manufacturing Process Patents and Patent Applications

The company also have know-how and patent applications that the company own which relate to the manufacture of its SPEAR T-cells. For example, Adaptimmune Therapeutics has filed patent applications in the major territories, which claim priority from initial priority patent applications filed at the USPTO and UKIPO, which are directed to a particular modification to the lentiviral vector technology. The company believe this modification enhances the safety profile of the lentiviral vector technology. A further patent application has been filed on enhancing the activity of its manufactured T-cells, and two further patent applications on increasing the efficiency of manufacture of its T-cell product are expected to be filed shortly.

Next Generation Approaches

Adaptimmune Therapeutics has recently filed a priority generating patent application in relation to a gene which prevents its cytotoxic T-cells from being inhibited by the immunosuppressive tumor microenvironment. A patent application under the applicable Patent Co-operation Treaty has since been filed claiming priority from that U.K. patent application and a patent application was filed in the US for accelerated prosecution under the Cancer Immunotherapy Pilot Program. This is potentially relevant to all of its SPEAR T-cells in solid tumor indications and protects one of the next generation SPEAR T-cell products under development.

Exclusive License for Bead Products

In December 2012, the company entered into two agreements, a license and a sub-license, with ThermoFisher Scientific Inc. (“ThermoFisher”). The license agreement grants it a field-based exclusive license under certain intellectual property rights owned or controlled by ThermoFisher in relation to the methods of use of the ThermoFisher Scientific Dynabeads® CD3/CD28 technology to isolate, activate and expand T cells and enable transfection of the T cells with any TCR genes to manufacture its licensed products and use and sell those TCR products to treat cancer, infectious disease and/or autoimmune disease. The licensed field relates to the ex-vivo activation and expansion of human T cells containing engineered TCRs for use as a therapy for treating cancer, infectious disease and/or autoimmune disease and where the therapy comprises the steps of (a) removing a sample containing T cells from a patient; (b) isolating T cells from that sample using the ThermoFisher bead product or similar magnetic beads; (c) transfecting those isolated T cells with a gene or genes encoding engineered TCRs of known antigen specificity; (d) activating and expanding the population of those engineered T cells using the ThermoFisher bead product or similar magnetic beads; and (e) introducing the expanded, engineered T cells back into the same patient. The license is not sub-licensable, but Adaptimmune Therapeutics is able to sub-contract manufacture of the licensed products to its contract manufacturing organizations. The company's sub-licensees have access to the required license directly from ThermoFisher under the above-described intellectual property rights on terms equivalent to those Adaptimmune Therapeutics has obtained from ThermoFisher in relation to its partnered licensed products.

Adaptimmune Therapeutics has granted an option under the license agreement to ThermoFisher to take an exclusive license under any improvements made by or for, or controlled by, it to the ThermoFisher patented technology to the extent any such improvements are dominated by the patent rights licensed to it. Any license will be outside of the exclusive field Adaptimmune Therapeutics has been granted, namely engineered T-cell therapy.

Under the license agreement, Adaptimmune Therapeutics has to demonstrate reasonable commercial efforts to carry out development and commercialization of the licensed products and Adaptimmune Therapeutics is required to make certain expenditures for research and development relating to the commercialization of the licensed products. This obligation is deemed satisfied upon first commercial sale of a licensed product. Adaptimmune Therapeutics has certain payment obligations under the license agreement including an upfront license fee of $335,000, which has already been paid, minimum annual royalty (in the low tens of thousands of U.S. dollars prior to licensed product approval and thereafter at a level of 50% of running royalties in the previous year), milestone payments (payable for each licensed product on achievement of certain development and commercialization milestones per licensed product) and a low single-digit running royalty payable on the net selling price of each licensed product. The license agreement will last until the expiration of the latest to expire of the licensed patent rights. The license agreement can be terminated before the end of its term by mutual agreement, by ThermoFisher on the occurrence of certain events (failure to use reasonable commercial efforts, willful making of a false statement of a material fact, breach of antitrust laws or other laws, material breach of the agreement, payment default or if Adaptimmune Therapeutics has challenged the validity or enforceability of any of the licensed patents). The license may also be terminated in the event of insolvency by either party.

The company also have a field-based exclusive sub-license under certain other patents which cover the method of use of the Dynabeads® CD3/CD28 and are controlled by ThermoFisher under a head-license from the University of Michigan, the U.S. Navy and the Dana-Farber Cancer Institute. The sub-license has the same relevant exclusivity scope and field-based restrictions and many of the terms are equivalent to those set out in the main license agreement with ThermoFisher, including the same requirement to demonstrate reasonable commercial efforts to carry out development and commercialization of the licensed products as in the main license agreement with ThermoFisher. Adaptimmune Therapeutics has certain payment obligations under the sub-license agreement including an upfront license fee of $665,000, which has already been paid, minimum annual royalty (in the tens of thousands of U.S. dollars prior to product approval and thereafter at a level of 50% of running royalties in the previous year), milestone payments (payable for each sub-licensed product on achievement of certain development and commercialization milestones per sub-licensed product) and a low single-digit running royalty payable on the net selling price of each sub-licensed product. The sub-license agreement will last until the expiration of the latest to expire of the sub-licensed patent rights. The sub-license agreement can be terminated before the end of its term by mutual agreement, by ThermoFisher or the head licensors on the occurrence of certain events (failure to use reasonable commercial efforts, willful making of a false statement of a material fact, failure to adequately meet any requirement for public use required under Federal regulations, breach of antitrust laws or other laws, material breach of the agreement, payment default or if Adaptimmune Therapeutics has challenged the validity or enforceability of any of the sub-licensed patents). The sub-license may also be terminated in the event of insolvency by either party. The sub-license has an additional requirement that any manufacture of engineered TCR products for sale in the United States must occur in the United States and reserves rights for the U.S. government to use the technology in accordance with 35 USC §200 et seq. and for the University of Michigan, and Dana-Farber Cancer Institute to use the technology for non-commercial research purposes. The aggregate milestone payments payable per product under the license and sub-license agreements do not exceed $5 million.

On June 16, 2016, the Company entered into a supply agreement with ThermoFisher for the supply of the Dynabeads® CD3/CD28 technology. The Dynabeads® CD3/CD28 technology is used in its manufacturing process to isolate, activate and expand patient T-cells. The supply agreement runs until December 31, 2025. Under the supply agreement, the Company is required to purchase its requirements for CD3/CD28 magnetic bead product exclusively from ThermoFisher for a period of 5 years and there are also minimum purchasing obligations. ThermoFisher has the right to terminate the supply agreement for material breach or insolvency.

Immunocore Limited

Adaptimmune Therapeutics has an assignment and license agreement in place with Immunocore that relates to certain co-owned patents, patent applications and rights in know-how that were originally developed by Avidex and subsequently acquired by Medigene. The patents, patent applications and rights in know-how are now fully co-owned by Adaptimmune and Immunocore. Each company utilizes the jointly owned patents and know-how within separate fields or applications, with its focus being on the treatment of patients with its SPEAR T-cells and Immunocore’s focus being on the treatment of patients with soluble TCRs. There are no termination rights in the assignment and license agreement.

See further “Related “Risk Factors—Risks Related to The company's Reliance Upon Third Parties—Adaptimmune Therapeutics has a shared development history with Immunocore and as a result jointly-own certainly intellectual property rights which are required for its ongoing business.”

Other Third-Party Intellectual Property Rights

Third-party patents do exist that purport to cover some or all of its current lentiviral vectors/systems or its process for manufacture. However, the majority of these patents will expire prior to any commercial supply by it of any TCR therapeutic candidates and the company do not currently require a license. Whether licenses are required under any remaining third-party patents or other third-party patents depends on what steps the company take going forward in relation to its lentiviral transduction process and manufacturing process. The company may, however, need to negotiate a license under any remaining third party patents or develop alternative strategies for dealing with any remaining third party patents if licenses are not available on commercially acceptable terms or at all.

From time to time, the company will use samples or cell lines obtained from third parties in order to identify either suitable targets or TCRs that bind to certain targets. The agreements under which samples are provided vary between third parties and certain third parties require entry into license agreements. These agreements may also contain payment obligations relating to the use of the various samples or the information obtained from use of those samples.

Competition

The biotechnology and pharmaceutical industries are characterized by rapidly advancing technologies, intense competition, a strong emphasis on proprietary products and intellectual property. While the company believe that its scientific knowledge, technology and development experience provide it with competitive advantages, the company face potential competition from many different sources, including major pharmaceutical, specialty pharmaceutical and biotechnology companies, academic institutions, governmental agencies and public and private research institutions. Any SPEAR T-cells that the company successfully develop and commercialize will compete with existing products and new products that may become available in the future.

Immunotherapy is an active area of research and a number of immune-related products have been identified in recent years that are alleged to modulate the immune system. Many of these products utilize dendritic cells, a form of immune cell that presents cancer target peptides to T cells and that can in turn result in T-cell activation. More recently, bi-specific antibodies and checkpoint inhibitors (for instance PD-1/PD-L1 antibodies) have been identified as having utility in the treatment of cancer. Bi-specific antibodies commonly target both the cancer peptide and the TCR, thus bringing both cancer cells and T cells into close proximity to maximize the chance of TCR binding and hence an immune response to the cancer cells. Checkpoint inhibitors on the other hand work by targeting receptors that inhibit T-cell effectiveness and proliferation and essentially activate T cells. Other immunotherapies that are being actively investigated include: antibody-drug complexes, TCR-mimic antibodies, oncolytic viruses, cancer vaccines. A variety of cell-based autologous and allogeneic approaches are also being researched and developed, including but not limited to: CAR-T cell, TCR T cell, GammaDelta T cell, CAR-NK cell, NK cell, NKT cell and CTL.

CAR-T in hematological malignancies: Engineered T cell therapeutics have been identified using antibody recognition systems engineered into T cells, so-called CAR-T cells. For the majority of approaches, CAR-T cells have access to extracellular proteins only and are independent of human leukocyte antigens (HLAs). A number of targets in hematological malignancies have been well characterized including, but not limited to: BCMA, CD4, CD5, CD19, CD22, CD20, CD33, CD38, CD70 and CD123. In 2017, the US FDA approved two CD-19 directed autologous CAR-T cell products, which are commercially available: Kymriah™ (tisagenlecleucel; Novartis) for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse, and Yescarta™ (axicabtagene ciloleucel) for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. In addition a number of pharmaceutical, biotechnology, and academic institutions are researching and developing autologous and allogeneic CAR-T therapies to a variety of target antigen. Many of these CAR-T cells in development are undergoing pivotal or Phase I/II clinical trials and some could seek marketing approval submissions during 2018 and beyond.CAR-T in solid tumors: In addition to hematological malignancies, there are a growing number of pharmaceutical, biotechnology, and academic institutions researching and developing autologous and allogeneic CAR-T therapies in the solid tumor setting. These CAR-T cell therapies are at a variety of stages of preclinical and clinical development, as well as directed towards a broad target spectrum, including but not limited to: EGFR, GD2, HER-2, IL13rα2, Lewis Y, L1-CAM, Mesothelin, MUC16, PSCA, PSMA and ROR1.CARs & TCR-mimics targeting peptide-HLA complexes: Most CAR-T therapies in development are directed towards antigen targets. However competitors are also developing a CAR-T that selectively binds to the peptide-HLA (pHLA) complex (the natural binding site for endogenous TCR). Furthermore, competitors are also looking at pHLA antibodies or TCR mimic antibodies that can either be engineered in T-cells or developed as standalone antibody therapies in cancer indications (both hematologic malignancies and solid tumors). Targets of such pHLA CAR-T or TCR mimic antibodies include: AFP, CD19, BCMA, NY-ESO-1, p53 and WT1.TCR T-cells: Competitors are developing TCR T-cells (including affinity engineered T-cells) that are directed towards a multitude of targets including: HPV-16 E6, KRAS, MAGE-A1, MAGE-A3, MAGE A3/A6, NY-ESO-1, PRAME and WT1. Juno Therapeutics has developed an engineered TCR therapeutic candidate where the end TCR is purported to have enhanced affinity through stem-cell selection. Juno’s candidate JTCR016 (WT1-specific TCR), in collaboration with Fred Hutchinson Cancer Research Center and the National Cancer Institute (NCI), is currently undergoing a Phase 1/2 trial in NSCLC and mesothelioma setting as well as a separate Phase 1/2 in AML. Data from the NSCLC trial is likely to emerge in 2018. Medigene AG has reported development of a PRAME TCR therapeutic candidate, which is due to begin Phase 1/2 clinical investigation in AML, MM and myelodysplastic syndromes.Other cell-based approaches: In addition to all the adoptive cell therapy approaches above, its competitors are also investigating the potential of GammaDelta T cell, CAR-NK cell, NK cell, NKT cell and CTLs either in a preclinical or clinical setting (both hematologic malignancies and solid tumors).

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Created by Asif Farooqui on 2019/09/06 05:29
     
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