On March 30, 2020 TCR2 Therapeutics Inc. (Nasdaq: TCRR), a clinical-stage immunotherapy company developing the next generation of novel T cell therapies for patients suffering from cancer, reported financial results for the fourth quarter and full year ended December 31, 2019 and provided a corporate update (Press release, TCR2 Therapeutics, MAR 30, 2020, View Source [SID1234555984]).

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"The past twelve months represent an exciting period for TCR2 as we advanced two programs into clinical trials. Last year we began using TC-210 to treat patients with mesothelin-positive solid tumors and, more recently, we initiated a Phase 1/2 trial of TC-110 in patients with CD19-positive hematological malignancies because we believe that TRuC-T cells alone can improve on the benefit provided by approved CAR-Ts," said Garry Menzel, Ph.D., President and Chief Executive Officer of TCR2 Therapeutics. "Looking ahead, 2020 is a pivotal year for the Company with interim Phase 1 data for both TC-210 and TC-110 as well as updates on new targets, our platform enhancements and allogeneic TRuC-T cells. With a year-end 2019 cash balance of $158.1 million, we are in a strong financial position to maintain runway into 2022 and execute on our strategic priorities."

"Commercially available CD19 CAR-Ts provide durable benefit in fewer than half of patients with lymphoma and their approval in acute lymphoblastic leukemia (ALL) remains limited to pediatric patients because they result in excessive toxicity in adult patients, as I witnessed while developing Kymriah," said Alfonso Quintás Cardama, M.D., Chief Medical Officer of TCR2 Therapeutics. "Our TRuC T-cells are more effective at trafficking in solid tumor models, which lymphoma tumors resemble, and are metabolically fitter than CAR-Ts, which enhances their ability to persist longer within the immunosuppressive solid tumor microenvironment. This gives us confidence that TC-110 may be more effective in treating patients with lymphoma and could allow us to salvage those who have previously failed CD19-directed CAR-Ts. In addition, we have shown that TRuC-T cells consistently release lower levels of cytokines in preclinical experiments, which could translate into a more favorable toxicity profile that would allow us to treat adult patients with ALL more safely."

Recent Developments

The U.S. Food and Drug Administration cleared the investigational new drug (IND) application for TC-110. TCR2 initiated its Phase 1/2 trial to treat patients with CD19-positive B-cell hematological malignancies, including adult acute lymphoblastic leukemia (aALL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and other non-Hodgkin lymphoma (NHL) subtypes.

TCR2 established operational capabilities at its manufacturing facility in Stevenage, UK and expects to use the facility to manufacture and supply clinical material after approval by the UK Medicines and Healthcare Regulatory Agency (MHRA).

TCR2 presented a poster at the 2020 Keystone Symposia Conference on Emerging Cellular Therapies: Cancer and Beyond highlighting allogeneic (off-the-shelf) T Cell Receptor Fusion Constructs (TRuC) T cells that lack alloreactivity and upregulate activation markers, secrete cytokines and kill tumor cells in an antigen-specific manner.

COVID-19 has significantly impacted the global healthcare system, including the conduct of clinical trials as medical institutions prioritize the treatment of those afflicted with COVID-19. As we balance the commitment to treat our cancer patients while mitigating the risk of viral spread to patients, employees and their families, we have instituted protective policies consistent with guidelines provided by the Centers for Disease Control and Prevention at all TCR2 facilities. While we are committed to providing an interim update of the Phase 1 portion of the TC-210 Phase 1/2 clinical trial in the second quarter of 2020 and the Phase 1 portion of the TC-110 Phase 1/2 clinical trial in the second half of 2020, the effect of the COVID-19 pandemic may impact the exact timing or content of these interim updates.

TC-110 Clinical Trial Design

The Phase 1/2 clinical trial is evaluating the safety and efficacy of TC-110, TCR2’s TRuC-T cell targeting CD19. The trial is enrolling patients with CD19-positive B-cell hematological malignancies including aALL, DLBCL, FL and other NHL subtypes.

In the Phase 1 portion of the clinical trial, patients will receive increasing TC-110 T cell doses following lymphodepleting chemotherapy. The primary objective of the Phase 1 portion of the study is to assess safety with a key secondary objective to determine the recommended Phase 2 dose (RP2D).

In the Phase 2 portion of the clinical trial, approximately 60 patients are planned to receive TC-110 at the RP2D and will be stratified according to their cancer diagnosis in three distinct cohorts: aggressive NHL, indolent NHL and aALL. Approximately 20 patients per indication will be infused with TC-110 T cells.

In addition to standard assessments of safety and efficacy, a panel of translational assays will be performed on patient samples throughout both phases of the study to assess, among others, cytokine production as well as expansion, trafficking, persistence, and changes in immunophenotype of TC-110 T cells.

TC-110 Patient Opportunity

Adult ALL

In 2019, there were an estimated 5,900 cases of ALL and over 1,500 related deaths in the United States. Adults comprise approximately 45% of all ALL cases but make up more than 85% of ALL-related deaths. CD19 directed CAR-Ts are not approved for patients with aALL.

DLBCL

In 2019 there were an estimated 74,000 new cases of NHL and 20,000 related deaths in the United States. Approximately two-thirds of patients with DLBCL are cured of their disease with frontline chemoimmunotherapy (R-CHOP). However, refractory patients have a median overall survival of only 6.3 months.

CD19-directed CAR-T cell therapy has shown activity in heavily pre-treated patients with CD19-positive DLBCL and two CAR-T cell therapies, Kymriah and Yescarta, have been approved for that indication. However, the response rate six months post-infusion ranges from 37% to 41% and both therapies are associated with high rates of severe CRS (13% to 23%) and neurotoxicity (12% to 28%).

Follicular Lymphoma

Approximately 15,000 patients were diagnosed in the United States with FL in 2019. The clinical course of patients with FL is generally indolent. However, 20% of patients with FL relapse within two years of R-CHOP therapy and have a median five-year survival rate of only 50% compared to 90% for the remaining 80% of

patients with a longer response duration. The experience with CAR-T cell therapy in FL is much more limited than in ALL or DLBCL.

Anticipated Milestones

TCR2 anticipates an interim update from the Phase 1 portion of the TC-210 Phase 1/2 clinical trial for patients with mesothelin-expressing solid tumors in 2Q20.

TCR2 anticipates an interim update from the Phase 1 portion of the TC-110 Phase 1/2 clinical trial for patients with CD19+ non-Hodgkin lymphoma or adult acute lymphoblastic leukemia in 2H20.

TCR2 anticipates clinical production of TRuC-T cells at its manufacturing facility in Stevenage, UK, in 2H20.

TCR2 anticipates advancing a third mono TRuC-T cell therapy in 2Q20 with a target IND filing in 1H21.

Financial Highlights

Cash Position: TCR2 ended 2019 with $158.1 million in cash, cash equivalents, and investments compared to $123.2 million as of December 31, 2018. Net cash used in operations was $41.4 million for 2019 compared to $18.7 million for 2018. TCR2 projects net cash use of $60-70 million for 2020.

R&D Expenses: Research and development expenses were $37.5 million for 2019 compared to $19.7 million for 2018. The increase in R&D expenses is primarily related to increase in headcount, activities related to the Phase 1/2 clinical trial of the Company’s lead solid tumor product candidate, TC-210, and activities related to the IND submission of the Company’s lead hematologic cancer product candidate, TC-110.

G&A Expenses: General and administrative expenses were $13.9 million for 2019 compared to $6.8 million for 2018. The increase in general and administrative expenses was primarily due to an increase in personnel costs and costs associated with operations as a public company.

Net loss: Net loss was $47.6 million for 2019 compared to $24.3 million for 2018, driven predominantly by increased R&D expense for 2019.

Upcoming Events

TCR2 Therapeutics management are scheduled to participate at the following upcoming conferences.

Goldman Sachs Cell Therapy Day: Alfonso Quintás Cardama, M.D., Chief Medical Officer of TCR2 Therapeutics, will present using a virtual platform on Monday, April 6, 2020 at 2:00pm ET