On November 18, 2024 Immatics N.V. (NASDAQ: IMTX, "Immatics" or the "Company"), a clinical-stage biopharmaceutical company active in the discovery and development of T cell-redirecting cancer immunotherapies, reported a business update and announced financial results for the quarter ended September 30, 2024 (Press release, Immatics, NOV 18, 2024, View Source [SID1234648470]). The Company also reported the first clinical data update from the ongoing Phase 1 dose escalation trial evaluating its next-generation, half-life extended TCR Bispecific molecule, TCER IMA402 targeting PRAME.
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"This year, Immatics has demonstrated the strength of its pipeline by announcing data on clinical activity for its four clinical-stage assets across two therapeutic modalities. These include ACTengine IMA203 targeting PRAME positioned in 2L+ melanoma now moving forward into the Phase 3 trial SUPRAME targeting BLA filing in early 2027; ACTengine IMA203CD8 targeting hard-to-treat solid cancers with an initial focus on ovarian and endometrial cancers; and TCER IMA401 targeting MAGEA4/8 demonstrating clinical proof-of-concept during dose escalation and positioned in squamous NSCLC and head and neck cancer. Today, we are very pleased to announce first clinical data on TCER IMA402 targeting PRAME, which show promising signals of anti-tumor activity during early dose escalation and is initially positioned in 1L+ melanoma," said Harpreet Singh, Ph.D., CEO and Co-Founder of Immatics. "With our enhanced cash runway into the second half of 2027, Immatics is well positioned to advance all four candidates to highly relevant value inflection points with a specific focus on delivering meaningful clinical signals in multiple solid cancers in the coming year."
Third Quarter 2024 and Subsequent Company Progress
TCR Bispecifics Programs
TCER IMA402 (PRAME)
Today, Immatics is providing the first clinical data update from the ongoing Phase 1 dose escalation trial evaluating its next-generation, half-life extended TCR Bispecific molecule, TCER IMA402 targeting PRAME.
Patient Population: As of the data cut-off on November 6, 2024, 33 heavily pretreated patients with recurrent and/or refractory solid tumors have been treated with a dose range from 0.02 mg to 4 mg of IMA402 monotherapy. The treated patient population is composed of patients with a median of three and a maximum of five lines of prior systemic treatments. The safety population includes all 33 patients treated with IMA402, of which 21 patients were evaluable for efficacy analysis and are PRAME-positive or were not tested for PRAME. Of these 21 patients, eight patients received at least one dose of IMA402 at dose level 7 (DL7, 3 mg), and one patient received IMA402 at dose level 8 (DL8, 4 mg). Based on preclinical in-vivo data, relevant anti-tumor efficacy was expected starting at ~3 mg human equivalent dose, which aligns with the initial clinical anti-tumor activity reported today.
Safety: IMA402 demonstrated a favorable tolerability profile in the 33 patients treated. The most common treatment-related adverse events (AEs) were mostly mild to moderate cytokine release syndrome (CRS) and transient lymphopenia. Step dosing has been implemented and dose escalation is ongoing. The maximum tolerated dose has not yet been determined.
Pharmacokinetics: Early pharmacokinetic data indicate a median half-life of approximately seven days, potentially enabling bi-weekly dosing.
Initial Anti-Tumor Activity: Initial signs of clinical activity have been observed and are associated with PRAME expression and IMA402 dose levels administered.
In the PRAME-negative patient population across all doses and indications, only one patient out of seven (14%) showed tumor shrinkage of -2.9%.
In comparison, in the PRAME-positive or non-tested patients across all indications treated with low dose levels (DLs 1-6), tumor shrinkage was observed in 25% (3/12) of patients, including one unconfirmed partial response in a cutaneous melanoma patient.
Nine patients with tumors that tested PRAME-positive or were not tested for PRAME received a relevant dose (8 patients at DL7 and 1 patient at DL8). 78% (7/9) thereof experienced shrinkage of their target lesions, including several patients with significant ongoing tumor shrinkage:
one cutaneous melanoma patient with an ongoing (at 3 months post first dose at data cut-off) confirmed partial response with -40.2% tumor shrinkage treated at DL7;
two patients with ongoing (at 6+ weeks and 8+ months) stable diseases with significant tumor shrinkage (-27.5% in a patient with cutaneous melanoma at DL8 and at first scan; -25% in a patient with uveal melanoma deepening over time and treated at escalating doses starting at DL4 and currently at DL7);
one ovarian cancer patient with ongoing (at 3 months) stable disease and tumor shrinkage of -13% started at DL6 and currently at DL7.
Early Signs of Clinical Activity Associated with PRAME Expression and IMA402 Dose
*Patients who received DL7 or higher, either from start or as part of intra-patient dose-escalation; #continuing treatment; PD: Progressive Disease; SD: Stable Disease; PR: Partial Response; cPR: confirmed Partial Response; BOR: Best Overall Response; BL: Baseline; NT: not tested or not evaluable for PRAME expression
More information and details on the IMA402 clinical data are available on the Events & Presentations page of the Immatics corporate website: View Source
Based on these initial signs of dose-dependent and PRAME target expression-dependent clinical activity observed during dose escalation, the Company will continue to evaluate IMA402 at higher dose levels to determine the optimal therapeutic dose. The next data update on IMA402 is planned for 2025.
TCER IMA401 (MAGEA4/8)
On September 16, 2024, Immatics announced the proof-of-concept clinical data for the first candidate of its next-generation, half-life extended TCR Bispecifics platform, TCER IMA401 (MAGEA4/8), during an oral presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2024.
As of data cut-off on July 23, 2024, 35 heavily pretreated patients with recurrent and/or refractory solid tumors were treated with IMA401 monotherapy across nine escalating dose levels. The treated patient population was composed of patients with 16 different solid tumor indications who were both HLA-A*02:01 and MAGEA4/8-positive, had received a median of four and up to eight lines of prior systemic treatments and the majority had an ECOG performance status of ≥ 1.
Proof-of-concept clinical data from the Phase 1a first-in-human dose escalation basket trial showed initial anti-tumor activity in multiple tumor types, durable objective responses, including confirmed responses ongoing at 13+ months, a manageable tolerability profile and a half-life of 14+ days.
Treatment with IMA401 monotherapy in patients with relevant IMA401 doses and MAGEA4/8high levels (N=17) demonstrated:
Objective response rate of 29% with confirmed responses observed in 25% of patients
Disease control rate of 53% and tumor shrinkage of 53%
As the clinical trial progresses, the Company aims to further leverage the potential of IMA401 by focusing on the enrollment of indications with high MAGEA4/8 target expression, such as lung and head and neck cancer patients, seeking to optimize the treatment schedule and also exploring the incremental clinical benefit available to patients through combining IMA401 with a checkpoint inhibitor. The next data update on IMA401 is expected in 2025.
ACTengine Cell Therapy Programs
ACTengine IMA203
On November 8, 2024, Immatics announced an expanded clinical dataset that included all infused patients in the Phase 1b dose expansion part of the trial (N=41), consisting of the 28 melanoma patients reported on October 10, 2024, and 13 non-melanoma patients, of which 10 non-melanoma patients were reported on November 8, 2023.
As of the data cut-off on August 23, 2024, treatment with IMA203 monotherapy in the melanoma patient population has demonstrated:
Confirmed objective response rate of 54% and an objective response rate of 62%
Disease control rate of 92% and tumor shrinkage in 88% of patients
12.1 months median duration of response, 6 months median progression-free survival and >1-year median progression-free survival in patients with deep responses
Median overall survival has not yet been reached
IMA203 monotherapy has maintained a favorable tolerability profile with no treatment-related Grade 5 events in the entire safety population (N=70 Phase 1a and Phase 1b patients across all dose levels and all tumor types).
Based on the Phase 1b data and discussions with the U.S. Food and Drug Administration, Immatics is on track to commence SUPRAME, the registration-enabling Phase 3 randomized-controlled clinical trial in melanoma for IMA203, in December 2024.
SUPRAME will evaluate IMA203 targeting PRAME in 360 HLA-A*02:01-positive patients with second-line or later (2L+) unresectable or metastatic melanoma who have received prior treatment with a checkpoint inhibitor. Patients will be randomized 1:1 for IMA203 or investigator’s choice of selected approved treatments in the 2L+ setting, including nivolumab/relatlimab, nivolumab, ipilimumab, pembrolizumab, lifileucel (U.S. only) or chemotherapy. The primary endpoint for full approval will be median PFS and secondary endpoints will include objective response rate, safety, duration of response, no overall survival detriment and patient-reported outcomes.
Patient enrollment for SUPRAME is forecast to be completed in 2026, and a pre-specified interim analysis is planned for early 2026. Immatics aims to submit a Biologics License Application (BLA) in early 2027 for full approval.
ACTengine IMA203CD8 (GEN2) monotherapy
On November 8, 2024, Immatics announced updated Phase 1 dose escalation clinical data on its next-generation ACTengine IMA203CD8 TCR-T cell therapy in 44 heavily pretreated HLA-A*02:01 and PRAME-positive patients with solid tumors, thereof 41 patients being evaluable for efficacy. Of note, these patients had been treated at substantially lower doses compared to IMA203 (GEN1), i.e. in a range of 0.2-0.48×109 TCR-T cells/m2 BSA (dose level 3) to 0.801-1.2×109 TCR-T cells/m2 BSA (dose level 4c) T cells infused.
As of the data cut-off on September 30, 2024, treatment with IMA203CD8 monotherapy demonstrated:
Confirmed objective responses observed in 41% of patients
Median duration of response of 9.2 months at a median follow-up of 13.1 months
Tumor shrinkage of 84% and disease control rate at week 6 of 85%
10 out of 17 responses were ongoing, of which three confirmed responses were ongoing at 14+, 15+ and 24+ months
Deep responses with ≥50% tumor size reduction were observed in 11 out of 17 responders. This group included two patients with complete response of target lesions, of which one patient showed a complete metabolic response according to PET-CT scan
IMA203CD8 monotherapy has maintained a manageable tolerability profile in the 44 patients treated.
Based on the enhanced pharmacology of IMA203CD8 demonstrated in this trial, the evaluation of higher doses of IMA203CD8 in the ongoing dose escalation trial opens the possibility of addressing hard-to-treat solid tumor indications with a medium-level of PRAME copy numbers, such as ovarian cancer and endometrial cancer.
Corporate Development
In September 2024, Immatics regained full clinical development and commercialization rights to IMA401 due to ongoing portfolio prioritization efforts within Bristol Myers Squibb. The Phase 1 dose escalation trial with IMA401 is ongoing and will continue to be conducted by Immatics.
Third Quarter 2024 Financial Results
Cash Position: Cash and cash equivalents as well as other financial assets total $549.2 million1 (€490.5 million) as of September 30, 2024, compared to $476.8 million1 (€425.9 million) as of December 31, 2023. The increase is mainly due to the public offering in January 2024, partly offset by ongoing research and development activities. Following the $150 million public offering in October 2024, the Company now projects a cash runway into the second half of 2027.
Revenue: Total revenue, consisting of revenue from collaboration agreements, was $56.7 million1 (€50.6 million) for the three months ended September 30, 2024, compared to $6.6 million1 (€5.9 million) for the three months ended September 30, 2023. The increase is mainly the result of a one-time revenue associated with the termination of the IMA401 collaboration by Bristol Myers Squibb during the three months ended September 30, 2024.
Research and Development Expenses: R&D expenses were $43.6 million1 (€38.9 million) for the three months ended September 30, 2024, compared to $34.1 million1 (€30.5 million) for the three months ended September 30, 2023. The increase mainly resulted from costs associated with the advancement of the clinical pipeline candidates.
General and Administrative Expenses: G&A expenses were $12.5 million1 (€11.2 million) for the three months ended September 30, 2024, compared to $10.0 million1 (€8.9 million) for the three months ended September 30, 2023.
Net Profit and Loss: Net loss was $9.6 million1 (€8.6 million) for the three months ended September 30, 2024, compared to a net loss of $29.7 million1 (€26.5 million) for the three months ended September 30, 2023. The decrease in net loss results from the increase in recognized revenue in the period.
Full financial statements can be found in the 6-K filed with the Securities and Exchange Commission (SEC) on November 18, 2024, and published on the SEC website under www.sec.gov.
Upcoming Investor Conferences
Jefferies London Healthcare Conference, London, United Kingdom – November 19 – 21, 2024
To see the full list of events and presentations, visit www.investors.immatics.com/events-presentations.
About IMA402
TCER IMA402 is a drug candidate owned by Immatics. IMA402 is Immatics’ second TCER molecule from the bispecifics pipeline and is directed against an HLA-A*02-presented peptide derived from preferentially expressed antigen in melanoma (PRAME), a protein frequently expressed in a large variety of solid cancers, thereby supporting the program’s potential to address a broad cancer patient population. Immatics’ PRAME peptide is present at a high copy number per tumor cell and is homogenously and specifically expressed in tumor tissue. The peptide has been identified and characterized by Immatics’ proprietary mass spectrometry-based target discovery platform, XPRESIDENT. IMA402 is part of Immatics’ strategy to leverage the full clinical potential of targeting PRAME, one of the most promising targets for TCR-based therapies.