On May 14, 2024 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 announced financial results for the quarter ended March 31, 2024 (Press release, Immatics, MAY 14, 2024, View Source [SID1234643224]).
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"Our lead cell therapy candidate, IMA203, continues to show deep and durable responses in a significantly expanded data set since our last data readout in November 2023. This update emphasizes the meaningful impact our novel immunotherapy may have on the lives of metastatic cutaneous, uveal and mucosal melanoma patients and the medical needs that IMA203 has a real opportunity to address. We continue to plan to move IMA203 into a registration-enabling clinical trial within this year while also continuing to ramp up our commercial manufacturing buildout," said Harpreet Singh, Ph.D., CEO and Co-Founder of Immatics. "In addition to IMA203’s progress, we also look forward to presenting the first clinical data on the two lead candidates from our bispecifics pipeline in the second half of the year."
First Quarter 2024 and Subsequent Company Progress
ACTengine Cell Therapy Program
ACTengine IMA203 monotherapy
Today, Immatics is providing a data update on IMA203 monotherapy targeting PRAME from the ongoing Phase 1 trial at the recommended Phase 2 dose (RP2D, 1 to 10 billion total TCR-T cells) in 30 heavily pretreated metastatic melanoma patients evaluable for efficacy. The treated patient population is composed of patients with a median of 3 lines of prior systemic treatments, consisting of cutaneous melanoma patients (N=17), uveal melanoma patients (N=10), mucosal melanoma patients (N=2) and a patient with melanoma of unknown primary (N=1). The current data represent an update to the previously communicated interim data readout in the IMA203 melanoma efficacy population of November 8, 2023.
As of the data cut-off on April 25, 2024, treatment with IMA203 monotherapy in the efficacy population has demonstrated:
Confirmed objective response rate (cORR) of 55% (16/29)
Disease control rate of 90% (27/30)
Tumor shrinkage in 87% (26/30) of patients
Median duration of response (mDOR) was 13.5 months (min 1.2+, max 21.5+ months) including 11 of 16 confirmed objective responses ongoing at data cut-off and longest duration of response ongoing at >21 months after infusion
Confirmed response rates are similar across all melanoma subtypes (56% (9/16) in cutaneous melanoma; 54% (7/13) in other melanoma subtypes)
To date, IMA203 has maintained a favorable safety profile with no treatment-related grade 5 events in the safety population (N=65 patients across all dose levels and all tumor types).
Best overall response for IMA203 at RP2D in melanoma
More information and details on the IMA203 clinical data update in melanoma are available in the Immatics corporate presentation: View Source
The next data update with translational and clinical data for IMA203 is planned for 2H 2024 at a medical conference.
Immatics’ late-stage clinical cell therapy development is supported by its differentiated manufacturing related to timeline, capabilities and facilities. ACTengine IMA203 cell therapy products are manufactured within 7 days, followed by a 7-day QC release testing at a success rate of >95% to reach the target dose. The company has also recently completed construction of a ~100,000 square foot R&D and GMP manufacturing facility with a modular design for efficient and cost-effective scalability intended to serve early-stage and Phase 2/3 clinical trials, as well as initial commercial supply. The new site will start GMP manufacturing of cell therapy products in early 2025. Meanwhile, the existing GMP facility, which is run in collaboration with UT Health, will remain active until YE 2025 and will also initially serve the Phase 2/3 registrational trial.
Following an RMAT designation in October 2023 and productive interactions with the FDA, Immatics plans to initiate a randomized Phase 2/3 trial in 4Q 2024 for IMA203 in patients with second-line or later (2L+) cutaneous melanoma, potentially also including uveal melanoma patients.
The Phase 2/3 trial is expected to assess IMA203 targeting PRAME in HLA-A*02:01-positive cutaneous melanoma patients versus a control arm. This approach is consistent with the FDA’s "one-trial" approach2, i.e., a single randomized controlled trial to support accelerated approval and the verification of clinical benefit to achieve full approval. The high prevalence of PRAME (≥95%) in cutaneous melanoma may enable the company to enroll patients without PRAME pre-testing. This would enhance trial operations and would remove the need to develop a companion diagnostic for PRAME testing in this indication. The full trial design is currently being developed and is subject to further alignment with the FDA as part of the ongoing discussions. Further details of the final clinical trial design will be provided in 2H 2024.
IMA203 is being developed to treat patients with metastatic melanoma, a prevalent cancer type with increasing incidence both inside and outside the United States. Currently, eligible PRAME-positive melanoma patients for the ongoing trials, i.e., 2L+, HLA-A*02:01 positive, include ~3,000 cutaneous melanoma patients and ~300 eligible uveal melanoma patients3 in the US.
ACTengine IMA203CD8 (GEN2) monotherapy
As of the previously reported interim clinical update from November 8, 2023, the first data on the company’s second-generation product candidate, IMA203CD8 (consisting of PRAME-specific functional CD8+ and CD4+ cells), demonstrated 56% (5/9) cORR with enhanced pharmacology compared to IMA203. mDOR was not reached (min 2.0+ months, max 11.5+ months) at a mFU of 4.8 months. As of the reported September 30, 2023, cut-off date, IMA203CD8 (GEN2) exhibited a manageable tolerability profile.
For IMA203CD8 (GEN2), Immatics cleared dose level 4a (DL4a, up to ~1.6×109 TCR-T cells) in December 2023. Immatics plans to continue dose escalation with the goal to define the optimal dose for further development. In addition to treating melanoma patients, Immatics has also started to expand its clinical footprint outside of melanoma to address a broader patient population with a particular focus on ovarian and uterine cancers.
A next data update for IMA203CD8 (GEN2) is planned for 2H 2024.
TCR Bispecifics Programs
Immatics’ T cell engaging receptor (TCER) candidates are next-generation, half-life extended TCR Bispecific molecules. They are designed to achieve a patient-convenient dosing schedule and to maximize efficacy while minimizing toxicities in patients through the proprietary format using a high-affinity TCR domain against the tumor target and a low-affinity T cell recruiter binding to the T cell.
Upcoming milestones for Immatics’ clinical TCER pipeline
Immatics seeks to deliver clinical proof-of-concept for its novel TCER platform as quickly as possible and plans to provide first clinical data for IMA401 (MAGEA4/8) and IMA402 (PRAME) in 2H 2024.
Key objectives include:
Demonstrating tolerability of the novel, next-generation, half-life extended TCR Bispecifics format;
Optimizing dosing schedule to a less frequent regimen during dose escalation based on pharmacokinetics data;
Demonstrating initial clinical anti-tumor activity (i.e., confirmed objective responses according to RECIST 1.1).
TCER IMA401 (MAGEA4/8)
The Phase 1 dose escalation basket 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 targets an HLA-A*02:01-presented peptide that occurs identically in two different proteins, MAGEA4 and MAGEA8. This target peptide has been selected based on natural expression in native solid tumors at particularly high target density (peptide copy number per tumor cell identified by Immatics’ proprietary quantitative mass spectrometry engine XPRESIDENT is >5x higher than for a MAGEA4 peptide target used in other clinical trials).
MAGEA4 and MAGEA8 are expressed in multiple solid cancers, including lung cancer, head and neck cancer, melanoma, ovarian cancer, sarcoma and others. Tolerability continues to be manageable with transient low-grade CRS, lymphopenia and neutropenia at high doses, all of which are expected for a bispecific T cell engager. A premedication with low doses of dexamethasone administered prior to the first 4 infusions, as used with other approved bispecific products, has been implemented as a preventative measure for continued dose escalation. Since the implementation of this premedication, to date, no cases of high-grade neutropenia among the patients treated have been observed. Based on pharmacokinetics data, the treatment schedule for IMA401 was switched from weekly to bi-weekly dosing. Confirmed objective responses have been observed in multiple patients.
IMA401 is being developed in collaboration with Bristol Myers Squibb. First clinical data in at least 25 patients in dose escalation across all doses and multiple solid cancers is expected to be announced in 2H 2024.
TCER IMA402 (PRAME)
Immatics initiated the Phase 1/2 trial investigating the company’s fully owned TCER candidate IMA402 in patients with recurrent and/or refractory solid tumors in August 2023 and the first patients have been dosed. Initial focus indications are ovarian cancer, lung cancer, uterine cancer and cutaneous and uveal melanoma, among others. IMA402 targets an HLA-A*02:01-presented peptide derived from the tumor antigen PRAME. This target peptide has been selected based on natural expression in native solid primary tumors and metastases at particularly high target density (peptide copy number per tumor cell identified by Immatics’ proprietary quantitative mass spectrometry engine XPRESIDENT).
Immatics has recently engaged Patheon UK Limited, a subsidiary of ThermoFisher Scientific Inc., for the manufacturing of clinical IMA402 batches for its use within a potential registration-enabling trial. Patient recruitment and dose escalation continue to scale. First clinical data in at least 15 patients in dose escalation across multiple solid cancers, but initially focused on melanoma, is anticipated to be announced in 2H 2024.
Corporate Development
On January 22, 2024, Immatics completed an offering of 18,313,750 ordinary shares at a public offering price of $11.00 per share. The gross proceeds from the offering, before deducting the underwriting discount and offering expenses, were approximately $201.5 million.
First Quarter 2024 Financial Results
Cash Position: Cash and cash equivalents, as well as other financial assets, total €564.0 million ($609.7 million1) as of March 31, 2024, compared to €425.9 million ($460.4 million1) 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. The company projects a cash runway into 2027.
Revenue: Total revenue, consisting of revenue from collaboration agreements, was €30.3 million ($32.8 million1) for the three months ended March 31, 2024, compared to €9.8 million ($10.6 million1) for the three months ended March 31, 2023. The increase is mainly the result of the release of the deferred revenue following the termination of the Genmab collaboration.
Research and Development Expenses: R&D expenses were €32.1 million ($34.7 million1) for the three months ended March 31, 2024, compared to €27.6 million ($29.8 million1) for the three months ended March 31, 2023. The increase mainly resulted from costs associated with the advancement of the clinical pipeline candidates.
General and Administrative Expenses: G&A expenses were €11.6 million ($12.5 million1) for the three months ended March 31, 2024, compared to €9.6 million ($10.4 million1) for the three months ended March 31, 2023.
Net Profit and Loss: Net loss was €3.1 million ($3.4 million1) for the three months ended March 31, 2024, compared to a net loss of €19.7 million ($21.3 million1) for the three months ended March 31, 2023. The decrease of net loss resulted mainly from the one-time revenue related to the termination of the Genmab collaboration, as reported previously.
Full financial statements can be found in the 6-K filed with the Securities and Exchange Commission (SEC) on May 14, 2024, and published on the SEC website under www.sec.gov.
Upcoming Investor Conferences
Bank of America Health Care Conference, Las Vegas (NV) – May 14 – 16, 2024
Jefferies Global Healthcare Conference, New York (NY) – June 5 – 7, 2024
To see the full list of events and presentations, visit www.investors.immatics.com/events-presentations.