On March 21, 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 provided financial results for the quarter and full year ended December 31, 2023 (Press release, Immatics, MAR 21, 2024, View Source [SID1234641327]).
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"Immatics kicked off 2024 with a successful capital raise, providing significant financial runway and additional momentum to advance our ongoing clinical cell therapy and bispecific trials," said Harpreet Singh, Ph.D., CEO and Co-Founder of Immatics. "We are striving to reach multiple relevant milestones this year, including announcing clinical proof-of-concept for our half-life extended TCR Bispecifics platform. In parallel, the clinical data for our PRAME cell therapy, IMA203 GEN1, in conjunction with highly constructive FDA discussions, reinforces our confidence in advancing this asset toward a registration-enabling Phase 2/3 clinical trial in melanoma, while laying the groundwork to transition into a fully equipped commercial-stage company."
Full Year 2023 and Subsequent Company Progress
ACTengine IMA203 (PRAME)
Clinical development plan update for ACTengine IMA203 GEN1 and IMA203CD8 GEN2 monotherapies
Following an RMAT designation in October 2023 and productive interactions with the FDA, Immatics plans to initiate a registration-enabling randomized Phase 2/3 trial in 2024 for IMA203 GEN1 in patients with second-line or later (2L+) cutaneous melanoma, potentially including also uveal melanoma patients.
Immatics intends to assess IMA203 GEN1 targeting PRAME in HLA-A*02:01-positive cutaneous melanoma patients versus a control arm. This single trial will be designed to support accelerated approval based on an interim readout and full approval based on overall survival. 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 could remove the need to develop a companion diagnostic 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. The Phase 2/3 trial is planned to start in 2024.
For IMA203CD8 GEN2, Immatics cleared dose level 4a (DL4a, up to ~1.6×109 TCR-T cells) in December 2023, which is currently intended to be the target 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 both Phase 1b cohorts with IMA203 GEN1 and IMA203CD8 GEN2 is planned for 2H 2024.
Manufacturing capabilities
Immatics’ late-stage clinical cell therapy development is supported by its streamlined manufacturing timeline, capabilities and facility. IMA203 GEN1 and IMA203CD8 GEN2 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 (IMA203 GEN1: RP2D; IMA203CD8: DL4a). 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 to serve early-stage and registration-enabling clinical trials, as well as potential initial commercial supply.
Interim clinical data update on ACTengine IMA203 GEN1 and IMA203CD8 GEN2 monotherapies, as of November 2023
On November 8, 2023, Immatics provided an interim clinical update from the ongoing Phase 1 trial with ACTengine IMA203 targeting PRAME in patients with recurrent and/or refractory solid cancers (data cut-off September 30, 2023). The update was focused on IMA203 GEN1 in melanoma patients at the recommended Phase 2 dose (RP2D, 1.0-10×109 total TCR-T cells) and the first clinical data for IMA203CD8 GEN2.
Treatment with IMA203 GEN1 monotherapy (consisting of PRAME-specific functional CD8+ cells) in Phase 1a and Phase 1b Cohort A at RP2D demonstrated durable objective responses in melanoma patients with one patient exceeding 12 months and two patients exceeding 15 months post infusion and a 50% (6/12) confirmed objective response rate (cORR). Median duration of response (mDOR) was not reached (min 2.2+ months, max 14.7+ months) at a median follow-up (mFU) of 14.4 months. In line with previous results, IMA203 GEN1 monotherapy was well tolerated at total doses of up to 10×109 TCR-T cells infused.
In addition, 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 GEN1. mDOR was not reached (min 2.0+ months, max 11.5+ months) at a mFU of 4.8 months. As of the reported cut-off date, IMA203CD8 GEN2 exhibited a manageable tolerability profile.
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 already 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 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). MAGEA4 and MAGEA8 are expressed in multiple solid cancers including lung cancer, head and neck cancer, melanoma, ovarian cancer, sarcoma and others. IMA401 is being developed in collaboration with Bristol Myers Squibb. First clinical data in at least 25 patients in dose escalation across 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 with a CDMO 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.
In January 2024, Immatics hired Jason Braun as Senior Vice President Commercial to support the company as it transitions into a fully equipped commercial-stage entity and targets the initiation of a registration-enabling Phase 2/3 trial for its PRAME TCR-T cell therapy. Jason Braun joins the company with more than 20 years of experience in the biotech and pharma industry, having worked with several biopharmaceutical companies including Amgen, Dendreon, Pharmacyclics (Abbvie), Kite (Gilead) and Nkarta, among others. During his career, he has established a successful track record in the commercialization of oncology drug candidates.
On September 11, 2023, Immatics announced a strategic multi-platform collaboration with Moderna, combining Immatics’ target and TCR platforms with Moderna’s cutting-edge mRNA technology. The collaboration spans various therapeutic modalities including bispecifics, cell therapy and cancer vaccines. Under the terms of the agreement, Immatics received an upfront payment of $120 million. In addition, Immatics will receive research funding and is eligible to receive development, regulatory and commercial milestone payments that could exceed $1.7 billion.
On July 24, 2023, Bristol Myers Squibb made a $35 million equity investment in Immatics, purchasing 2,419,818 ordinary shares in a private placement transaction at a subscription price per share of $14.46.
In May 2023, Bristol Myers Squibb exercised its first option and entered into a global license agreement with Immatics for the most advanced TCR-T product candidate. As part of the agreement, 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.
Full Year 2023 Financial Results
Cash Position: Cash and cash equivalents as well as other financial assets total €425.9 million ($470.6 million1) as of December 31, 2023, compared to €362.2 million ($400.2 million1) as of December 31, 2022. The increase is mainly due to upfront payments for collaborations, partly offset by our ongoing research and development activities. This does not include the net proceeds received in January 2024 from the public offering. Adding these proceeds, the company currently projects a cash runway into 2027.
Revenue: Total revenue, consisting of revenue from collaboration agreements, was €54.0 million ($59.7 million1) for the year ended December 31, 2023, compared to €172.8 million ($190.9 million1) for the year ended December 31, 2022. The decrease is mainly the result of a one-time revenue for the license portion of the IMA401 collaboration with Bristol Myers Squibb for the year ended December 31, 2022.
Research and Development Expenses: R&D expenses were €118.7 million ($131.2 million1) for the year ended December 31, 2023, compared to €106.8 million ($118.0 million1) for the year ended December 31, 2022. The increase mainly resulted from costs associated with the advancement of the clinical pipeline of ACTengine and TCER candidates.
General and Administrative Expenses: G&A expenses were €38.2 million ($42.2 million1) for the year ended December 31, 2023, compared to €36.1 million ($39.9 million1) for the year ended December 31, 2022.
Net Profit and Loss: Net loss was €97.0 million ($107.2 million1) for the year ended December 31, 2023, compared to a net profit of €37.5 million ($41.4 million1) for the year ended December 31, 2022. The decrease of net profit 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 for the year ended December 31, 2022.
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.
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.