On March 21, 2023 Immatics N.V. (NASDAQ: IMTX; "Immatics"), a clinical-stage biopharmaceutical company active in the discovery and development of T cell-redirecting cancer immunotherapies, reported a business update and reported financial results for the quarter and full year ended December 31, 2022 (Press release, Immatics, MAR 21, 2023, View Source [SID1234629098]).
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Harpreet Singh, Ph.D., CEO and Co-Founder of Immatics commented, "Our ACTengine IMA203 clinical trial has gained significant traction over the past year with promising data for our
1 Clinical Trial Application (CTA) is the European equivalent of an Investigational New Drug (IND) application
2 All amounts translated using the exchange rate published by the European Central Bank in effect as of December 31, 2022 (1 EUR = 1,0666 USD).
Immatics Press Release March 22, 2023
monotherapy candidate targeting PRAME. As we continue demonstrating the potential of our first- and second-generation product candidates in patients, we have commenced establishing our in-house GMP cell therapy manufacturing facility in Houston, TX. This positions us to scale our cell therapies for registration-directed trials and commercial supply. In addition, we have significantly advanced our clinical TCR Bispecifics pipeline with one TCER program targeting MAGEA4/8 now in the clinic and a second TCER program targeting PRAME commencing clinical studies this year. We demonstrated our ability to execute and deliver on our goals in 2022 and look forward to continuing on this path in 2023."
Full Year 2022 and Subsequent Company Progress
Adoptive Cell Therapy Programs
· ACTengine IMA203 (PRAME) – Immatics is investigating IMA203 TCR-T in a Phase 1b trial including three ongoing dose expansion cohorts. Immatics’ focus for 2023 is to advance its monotherapy product candidates, 1st-generation IMA203 TCR-T (Cohort A) and 2nd-generation IMA203CD8 TCR-T (Cohort C) in the last-line therapy setting. Data generated throughout 2023 with longer follow-up to assess durability of response is intended to identify the most promising cohort to advance towards pivotal trials and potential commercialization. The clinical data update on all three cohorts is planned for 2H 2023.
IMA203 TCR-T monotherapy (Cohort A):
o In October 2022, Immatics provided an interim update on the ongoing IMA203 TCR-T monotherapy trial covering data from 27 patients in the completed Phase 1a dose escalation and the first 5 patients in the Phase 1b dose expansion trial.
o Treatment with IMA203 continued to show a manageable tolerability profile in a heavily pre-treated patient population.
o A confirmed objective response rate (cORR) of 50% (6/12) was observed at target dose or above across Phase 1a and Phase 1b.
o Confirmed responses were observed in 4/5 (80%) patients in the Phase 1b trial alone with early signs of prolonged durability at 12 weeks of follow-up with all responses ongoing at data cut-off.
o Manufacturing enhancements implemented in Phase 1b (including monocyte depletion) resulted in higher infused T cell doses and significantly higher T cell peak expansion and persistence.
o Confirmed responses were observed across different solid tumor types: cutaneous melanoma, ovarian cancer, head and neck cancer, uveal melanoma, and synovial sarcoma.
Immatics Press Release March 22, 2023 2 | 13
IMA203 TCR-T in combination with nivolumab (Cohort B):
o In May 2022, the first patient was treated with IMA203 in combination with the PD-1 immune checkpoint inhibitor nivolumab at the provisional recommended Phase 2 dose (RP2D).
o Immatics is currently prioritizing patient treatment with IMA203 and IMA203CD8 TCR-T monotherapy in a last-line therapy setting but is considering further investigation of a combination with nivolumab as a front-line therapy.
IMA203CD8 2nd-generation TCR-T monotherapy (Cohort C):
o IMA203CD8 is Immatics’ 2nd-generation monotherapy product candidate directed against PRAME in which IMA203 engineered T cells are co-transduced with a CD8αβ co-receptor that engages functional CD4 and CD8 T cells.
o The first patient was treated in August 2022. As IMA203CD8 is a novel product candidate under a new IND amendment, a staggered enrollment was implemented; the treatment of three patients at dose level 3 (DL3) has been completed. Patients are currently being treated at DL4a (up to 0.8×109 TCR-T cells/m2 body surface area).
· Cell Therapy Manufacturing – Immatics is further enhancing its cell therapy manufacturing process and capabilities.
o Immatics proprietary manufacturing process is designed to produce T cells within one week, followed by a recently implemented one-week quality control release testing (previously two weeks). This allows Immatics to shorten the turnaround time and to provide the cell therapy product candidate to patients faster.
o Immatics is building a state-of-the-art 100,000 square foot research and commercial GMP manufacturing facility in the metropolitan area of Houston, Texas. The facility is intended to manufacture Immatics’ ACTengine IMA203 products as well as other future autologous and allogeneic cell therapy product candidates for early-stage and registration-directed clinical trials as well as for initial commercial supply. The facility is designed for flexibility and can be expanded in a modular fashion. The GMP manufacturing facility is expected to be operational in 2024.
· ACTengine IMA201 (MAGEA4/8) – The Phase 1a dose escalation cohort at target dose is ongoing. Immatics plans to discontinue this program after treatment of the remaining patients already enrolled in the clinical trial in order to focus on its TCR Bispecific program TCER IMA401 addressing the identical target peptide derived from MAGEA4/8 as IMA201.
· ACTengine IMA204 (COL6A3 exon 6) – Immatics and the University of Pennsylvania co-authored a research paper published in the peer-reviewed journal, Science Translational Medicine highlighting the identification of a novel proprietary HLA-A*02:01-presented target,
Immatics Press Release March 22, 2023
collagen type VI alpha-3 (COL6A3) using Immatics’ proprietary discovery platforms, XPRESIDENT and XCEPTOR. COL6A3 is expressed at high target density across multiple solid cancer indications and specific to the tumor stroma. Targeting tumor stroma provides an innovative therapeutic opportunity to disrupt the tumor microenvironment. The COL6A3-directed TCR-T candidate ACTengine IMA204, developed by Immatics, was able to eliminate tumor cells at physiological target levels in in vitro studies and in vivo mouse models. The company has delayed the IND submission for IMA204 to consolidate its clinical resources on accelerating the clinical development of its PRAME-directed product candidates.
· ACTallo pipeline – In June 2022, Immatics entered into two strategic collaborations with the goal of developing transformative next-generation allogeneic gamma delta TCR-T/CAR-T programs with enhanced persistence, safety and potency, by combining Immatics’ proprietary ACTallo platform with Bristol Myers Squibb’s next-generation technologies and Editas Medicine’s CRISPR gene editing technology.
o Immatics entered into a new multi-program collaboration with Bristol Myers Squibb to develop allogeneic TCR-T/CAR-T programs using Immatics’ proprietary ACTallo platform and Bristol Myers Squibb’s technologies. Immatics received $60 million upfront payment and is eligible for up to $700 million per program in milestone payments as well as tiered royalties. Immatics may also develop its own ACTallo-based programs outside of the collaboration.
o The strategic research collaboration and licensing agreement with Editas Medicine, Inc., combines Immatics’ ACTallo platform with Editas Medicine’s CRISPR gene editing technology.
Autologous TCR-T pipeline
· Immatics and Bristol Myers Squibb expanded their autologous T cell receptor-based therapy (TCR-T) collaboration signed in 2019 by including one additional TCR-T target discovered by Immatics. Immatics received an upfront payment of $20 million and is eligible for milestone payments as well as royalties.
· In October 2022, GSK provided Immatics with notice of its decision to terminate their collaboration. Initially announced on February 20, 2020, the terms of the agreement included a €45 million (~$50 million) upfront payment to Immatics and the potential for additional milestone and royalty payments in return for access to two of Immatics’ TCR-T programs. As communicated to Immatics, GSK’s decision was made unrelated to the programs and the progress achieved in the collaboration to date. The termination was effective on December 26, 2022. GSK transferred the rights for both TCR-T programs back to Immatics.
Immatics Press Release March 22, 2023
TCR Bispecifics Programs
Immatics’ TCER candidates are next-generation, half-life extended TCR Bispecific molecules designed to maximize efficacy while minimizing toxicities in patients through its proprietary format using a low-affinity T cell recruiter and a high-affinity TCR domain.
· TCER IMA401 (MAGEA4/8) – Immatics initiated a Phase 1 trial in May, to evaluate safety, tolerability and initial anti-tumor activity of its T cell engaging receptor (TCER) IMA401 for patients with recurrent and/or refractory solid tumors. IMA401 is being developed in collaboration with Bristol Myers Squibb.
· TCER IMA402 (PRAME) – A comprehensive preclinical data set was presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) congress in September 2022. The TCER candidate IMA402 showed potent and selective activity against PRAME-positive tumor cell lines in vitro, high anti-tumor activity in in vivo mouse models, low target-independent T cell engager-associated cytokine release and favorable pharmacodynamic characteristics. The submission of the CTA1 application for the Phase 1/2 trial is on track for 2Q 2023. Immatics plans to start the trial in 2H 2023 with a flexible dose escalation scheme for accelerated clinical development.
· TCER IMA403 and TCER IMA40x – Immatics continues to develop several innovative preclinical TCER product candidates against so far undisclosed targets for their proprietary and/or partnered pipeline. IMA403 is in advanced preclinical development with proof-of-concept studies ongoing. Additionally, TCER engineering and preclinical testing is ongoing for further TCER candidates, IMA40x, targeting peptides presented by HLA-A*02:01 and other HLA-types.
Corporate Development
· Immatics successfully completed an underwritten public offering in October 2022, raising approximately $110 million before deducting underwriting discount and offering expenses. The offering included participation from investors including Armistice Capital Master Fund Ltd., Dellora Investments, EcoR1 Capital, Nantahala Capital, Perceptive Advisors, Rock Springs Capital, RTW Investments, LP, Samsara BioCapital, SilverArc Capital, Sofinnova Investments, Wellington Management, 683 Capital and other specialist biotech investors.
· Pursuant to Dievini Hopp Biotech Holding’s rights under the business combination in 2020, dievini has designated Mathias Hothum, Ph.D., for election as a director at the 2023 annual general meeting of the shareholders in June 2023, as successor to Friedrich von Bohlen und Halbach, Ph.D. Dr. Hothum has been the Managing Director of dievini Hopp Biotech Holding, which manages the life science activities and investments of Dietmar Hopp and his family. He is also the Managing Director of several investment and consulting companies. Dr. Hothum holds a Ph.D. in Pharmaceutical Economics and Medical Sociology from the University of Magdeburg, Germany.
Immatics Press Release March 22, 2023
Full Year 2022 Financial Results
Cash Position: Cash and cash equivalents as well as other financial assets total €362.2 million ($386.3 million2) as of December 31, 2022 compared to €145.1 million ($154.8 million2) as of December 31, 2021. The increase is mainly due to our public offering and upfront payments for collaborations, partly offset by our ongoing research and development activities. The Company projects a cash runway into 2025.
Revenue: Total revenue, consisting of revenue from collaboration agreements, was €172.8 million ($184.3 million2) for the year ended December 31, 2022, compared to €34.8 million ($37.1 million2) for the year ended December 31, 2021.
Research and Development Expenses: R&D expenses were €106.8 million ($113.9 million2) for the year ended December 31, 2022, compared to €87.6 million ($93.4 million2) for the year ended December 31, 2021. 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 €36.1 million ($38.5 million2) for the year ended December 31, 2022, compared to €33.8 million ($36.1 million2) for the year ended December 31, 2021.
Net Profit and Loss: Net profit was €37.5 million ($40.0 million2) for the year ended December 31, 2022, compared to a net loss of €93.3 million ($99.5 million2) for the year ended December 31, 2021. The improvement resulted mainly from the one-time license fee income in connection with the IMA401 collaboration with Bristol Myers Squibb, as well as the recognition of remaining deferred revenue in connection with the termination of the GSK collaboration.
Full financial statements can be found in the Annual Report on Form 20-F filed with the Securities and Exchange Commission (SEC) and published on the SEC website under www.sec.gov.
2 All amounts translated using the exchange rate published by the European Central Bank in effect as of December 31, 2022 (1 EUR = 1,0666 USD).
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Immatics Press Release March 22, 2023