Harpreet Singh, Ph.D., CEO and Co-Founder of Immatics commented, “We commenced 2023 with significant advances in our ACTengine® IMA203 clinical trial, announcing encouraging data demonstrating that IMA203 is able to drive deep and durable responses independent of tumor type, with some responses ongoing beyond 9 months after treatment. As we continue to leverage the multi-cancer PRAME opportunity, we are pleased to have filed a CTA for IMA402, moving our second TCR Bispecifics candidate toward clinical evaluation. We look forward to providing a next update on our IMA203 TCR-T therapy candidates as well as announcing a potential fast-to-market pathway by the end of the year.”

First Quarter 2023 and Subsequent Company Progress

Adoptive Cell Therapy Programs

ACTengine® IMA203 TCR-T monotherapy (Phase 1b Cohort A):

• On May 2^nd, Immatics provided an interim update covering data from 11 heavily pre-treated patients in Phase 1b dose expansion Cohort A (monotherapy). Patients were infused with IMA203 TCR-T cells at dose level (DL) 4 or DL5 with a mean total infused dose of 3.67x10⁹ TCR-T cells (range 1.30-8.84x10⁹ TCR-T cells).
• Treatment with IMA203 in Cohort A (monotherapy) continues to show manageable tolerability at doses of up to approximately 9 billion CD8+ TCR-T cells; no high-grade cytokine release syndrome (CRS) and no immune effector cell associated neurotoxicity syndrome (ICANS) observed in the 11 patients treated in Cohort A; no dose-dependent increase of CRS observed.
• All 11 patients experienced expected cytopenia (Grade 1-4) associated with lymphodepletion. 10 patients (91%) had a low to moderate (Grade 1-2) cytokine release syndrome (CRS), of which 5 patients (45%) had Grade 1, and 5 patients (45%) had Grade 2 CRS.
• Objective responses were observed in last-line solid cancer patients including cutaneous melanoma, ovarian cancer, uveal melanoma, head and neck cancer and synovial sarcoma.
• Initial objective response rate (ORR) of 64% (7/11) was observed at ~week 6 (partial responses (PR) according to RECIST 1.1).
• Confirmed ORR of 67% (6/9) was observed at ~month 3; initial responses at week 6 were confirmed for all 6 responders with an available subsequent 3-month scan.
• Median duration of response² was not reached (min 1.3+ months, max 8.8+ months) at a median follow-up³ of 8.5 months; two confirmed partial responses (cPR) ongoing at more than 9 months after treatment as well as three additional ongoing responses at 6+ months, ~3 months and 6+ weeks.
• Objective responses were observed independent of solid tumor type at low, medium and high PRAME expression levels above Immatics’ MS-guided RNA threshold.

In addition to Cohort A (IMA203 monotherapy), ACTengine® IMA203 TCR-T is currently being evaluated in two additional ongoing Phase 1b dose expansion cohorts:

• Cohort B: IMA203 in combination with an immune checkpoint inhibitor. Cohort B is focused on generating safety data for potential further investigation of a combination approach as a front-line therapy.
• Cohort C: IMA203CD8 TCR-T monotherapy, where IMA203 engineered T cells are co-transduced with a CD8αβ co-receptor. IMA203CD8 is currently being explored in DL4a (up to 0.8x10⁹ TCR-T cells/m² BSA).
• Immatics has prioritized patient treatment with IMA203 and IMA203CD8 TCR-T monotherapy in the last-line therapy setting.
• Next update on Immatics’ IMA203 Phase 1b cohorts, including the projected clinical development path for PRAME TCR-T monotherapy towards registration-directed trials and potential commercialization is planned for 4Q 2023. Immatics’ IMA203 development strategy to realize the multi-cancer opportunity PRAME is based on two pillars aimed:  
  • initially at a (1) fast-to-market approach in 1-2 last-line solid cancer types with high PRAME prevalence and where clinical proof-of-concept has been demonstrated, such as cutaneous melanoma (potentially bundled with uveal melanoma) and/or ovarian cancer and
  • later at a (2) planned broad development with expansion to other cancer types, such as uterine cancer, lung cancer, breast cancer, head and neck cancer and other tumor types having a broad patient reach.
• Immatics is currently building a state-of-the-art facility designed to manufacture ACTengine® IMA203 TCR-T products, as well as other cell therapy candidates, for registration-directed trials and initial commercial supply. The facility is expected to be operational in 2024.
   

Autologous TCR-T pipeline

• Bristol Myers Squibb exercised its first option and entered into a global license agreement with Immatics for the most advanced TCR-T product candidate from the 2019 multi-target strategic collaboration to develop four TCR-based adoptive cell therapies targeting solid tumors.
• Immatics received an option payment of $15 million and is eligible for up to $490 million in milestone payments in addition to tiered royalties on net sales of the product.

TCR Bispecifics Programs

Immatics’ T cell engaging receptor (TCER®) candidates are next-generation, half-life extended TCR Bispecific molecules designed to maximize efficacy while minimizing toxicities in patients through Immatics’ proprietary format using a low-affinity T cell recruiter and a high-affinity TCR domain.

• TCER® IMA401 (MAGEA4/8) – Phase 1 trial to evaluate safety, tolerability and initial anti-tumor activity of TCER® IMA401 in patients with recurrent and/or refractory solid tumors is ongoing. IMA401 is being developed in collaboration with Bristol Myers Squibb.
   
• TCER® IMA402 (PRAME) – Immatics submitted a clinical trial application (CTA⁴) to the Paul-Ehrlich-Institute (PEI) on April 14, 2023, to initiate the Phase 1/2 trial investigating IMA402 in patients with recurrent and/or refractory solid tumors. The trial is expected to commence in 2H 2023 with a first clinical data interim report planned in 2024.
   

Corporate Update

• Nancy Valente, M.D., resigned from her position on Immatics’ Board of Directors effective May 12, 2023. Nancy has been appointed as Chief Development Officer at Xencor Inc.. Immatics would like to thank Nancy Valente for her valuable contributions during her time on Immatics' Board of Directors.
   

First Quarter 2023 Financial Results

Cash Position: Cash and cash equivalents as well as other financial assets total €329.8 million ($358.7 million¹) as of March 31, 2023, compared to €362.2 million ($393.9 million¹) as of December 31, 2022. The decrease is mainly due to our ongoing research and development activities. The Company continues to project a cash runway into 2025.

Revenue: Total revenue, consisting of revenue from collaboration agreements, was €9.8 million ($10.7 million¹) for the three months ended March 31, 2023, compared to €102.9 million ($111.9 million¹) for the three months ended March 31, 2022. The decrease is mainly related to the recognition of revenue for the license portion of the collaboration agreement with Bristol Myers Squibb on IMA401 during the three months ended March 31, 2022.

Research and Development Expenses: R&D expenses were €27.6 million ($30.0 million¹) for the three months ended March 31, 2023, compared to €25.1 million ($27.3 million¹) for the three months ended March 31, 2022. The increase mainly resulted from higher costs associated with the advancement of the clinical and pre-IND pipeline of ACTengine® and TCER® candidates.
General and Administrative Expenses: G&A expenses were €9.6 million ($10.4 million¹) for the three months ended March 31, 2023, compared to €9.3 million ($10.1 million¹) for the three months ended March 31, 2022.

Net Profit and Loss: Net loss was €19.7 million ($21.4 million¹) for the three months ended March 31, 2023, compared to a net profit of €85.7 million ($93.2 million¹) for the three months ended March 31, 2022. The decrease resulted mainly from the one-time license fee income in connection with the IMA401 collaboration with Bristol Myers Squibb during the three months ended March 31, 2022.