Immatics N.V. Stock

Immatics N.V., a clinical-stage biotechnology company, engages in the development of T cell receptor (TCR)-based immunotherapies for the treatment of cancer.

The company engages in the development of product candidates for the treatment of patients with solid tumors, who are inadequately served by existing treatment modalities. The company strives to become an industry leading, fully integrated global biopharmaceutical company engaged in developing, manufacturing and commercializing TCR immunotherapies.

By utilizing TCR-based therapeutics, the company is able to direct T cells to intracellular cancer targets that are not accessible through classical antibody-based or CAR-T therapies.

The company is developing its targeted immunotherapy product candidates through two distinct treatment modalities: TCR-engineered autologous (ACTengine) or allogeneic (ACTallo) Adoptive Cell Therapies (ACT) and antibody-like Bispecifics, also called T cell Engaging Receptors (TCER). Each modality is designed with distinct attributes and mechanisms of action to produce the desired therapeutic effect for a variety of cancer patient populations with different unmet medical needs. The company’s pipeline shown below comprises several proprietary TCR-based product candidates in clinical and preclinical development. In addition to its proprietary pipeline, the company is collaborating with industry-leading partners, including Bristol Myers Squibb (BMS), Editas Medicine and Genmab, to develop multiple additional therapeutic programs covering ACT and Bispecifics.

The company is ideally positioned to comprehensively address the needs of solid tumor patients with its TCR-based therapeutic approaches: ACTengine TCR-engineered T cells (TCR-T) have already shown strong clinical activity in patients with high tumor burden.

In addition to its autologous ACTengine product candidates the company is building an allogeneic platform (ACTallo) based on allogeneic (i.e. third-party donor-derived) gamma delta T cells. ACTallo is advancing the cell therapy concept beyond individualized manufacturing and is being developed to generate an off-the-shelf cell therapy.

ACTengine TCR-T Product Candidates

The company’s ACTengine programs are based on genetically engineering a patient’s own, autologous T cells with novel TCRs designed to recognize a specific cancer target on the tumor. The engineered T cells (TCR-T) are intended to induce a robust and specific anti-tumor attack to fight the cancer.

ACTengine IMA203 – TCR-T Targeting PRAME

The company’s lead autologous TCR-T program, ACTengine IMA203, is directed against an HLA-A*02:01-presented peptide derived from PRAME, one of the most prevalent solid tumor targets known to date. PRAME is frequently expressed in solid tumors, such as melanoma, uveal melanoma, uterine cancers, ovarian cancer, subtypes of sarcoma, squamous NSCLC, TNBC, head and neck cancer and others, thereby supporting its program’s potential to address a broad cancer patient population. The company’s 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 the company’s proprietary mass spectrometry-based target discovery platform XPRESIDENT. Through its proprietary TCR discovery and engineering platform XCEPTOR, the company has generated a highly specific TCR against this target for its use as TCR-based cell therapy approach ACTengine IMA203.

The company’s proprietary manufacturing process is designed to expand and engineer T cells within one week. This process is followed by release testing. The company has recently implemented an expedited quality control release testing of one week which allows it to provide the cell products to patients faster. T cells, which are a subset of PBMCs, are activated and subsequently mixed with a lentiviral vector to transduce the T cells with the PRAME-specific TCR. The engineered T cells are then expanded in the presence of cytokines, concentrated and frozen before undergoing release testing. The resulting cell product is then stored frozen until the patient is ready to receive the treatment. T cells can be shipped frozen (frozen-in-frozen-out) for both delivery of the patient’s cells to its manufacturing site and shipment of the T cell product to the clinical site.

The company is evaluating ACTengine IMA203 TCR-T in an ongoing Phase 1b trial including three expansion cohorts which have all been initiated during the first half of 2022 and build upon the promising early clinical results during its Phase 1a trial:

On October 10, 2022, the company announced a clinical data update for the 1st-generation IMA203 TCR-T monotherapy covering:

The completed Phase 1a dose escalation part of the clinical trial, during which the company treated 27 patients, including 7 patients at the provisional recommended Phase 2 dose (RP2D) (being dose level 4). The Phase 1a patients were heavily pre-treated, had a particularly high baseline tumor burden and an average of 4.2 prior lines of treatment, and patients treated at the RP2D had an average of 4.6 prior lines of treatment.

Initial data from the first 5 patients in the ongoing Phase 1b dose expansion Cohort A (monotherapy). These Phase 1b patients were heavily pre-treated, had high to moderate baseline tumor burden and an average of 4.0 prior lines of treatment.

The company observed a higher overall response rate (ORR) and confirmed ORR (cORR) in patients who received doses above 1 billion TCR-T cells, being dose levels 4 and 5.

The company observed confirmed objective responses in patients with a broad spectrum of different tumor types, including cutaneous melanoma, ovarian cancer, head and neck cancer, uveal melanoma and synovial sarcoma.

The company is transitioning to an indication-specific development strategy for its IMA203 TCR-T trial based on PRAME prevalence, patient population size and observed responses. As a first step the company will focus on indications with PRAME prevalence above 80%, such as cutaneous melanoma, uveal melanoma, ovarian and uterine carcinoma, as well as uterine carcinosarcoma, where it can quickly initiate registration trials in an effort to progress toward marketing authorization as efficiently as possible. The company is also planning to expand to other indications, such as head and neck cancer, where it has reported responses, lung cancer and TNBC.

In addition to Cohort A, evaluating IMA203 TCR-T as monotherapy, the company is investigating IMA203 in two additional Phase 1b dose expansion cohorts to realize the full clinical potential of IMA203 TCR-T targeting PRAME. The company is prioritizing treatment of patients within the 1st and 2nd-generation IMA203 TCR-T monotherapy cohorts.

ACTengine IMA201 TCR-T targets an HLA-A*02:01-presented peptide derived from the tumor antigen MAGEA4 and/or MAGEA8 and is being evaluated at target dose level in a Phase 1a dose escalation cohort. XPRESIDENT quantitative information on target density (copy number per tumor cell) between peptides originating from the same source protein allows identification of the most relevant targets. By comparing MAGEA4 vs. MAGEA4/A8 peptide presentation on the same tumor samples, the company determined that the selected MAGEA4/8 peptide is presented at >5-fold higher target density than a commonly targeted MAGEA4 peptide.

The company’s ACTengine program IMA204 is directed against COL6A3 exon 6, a novel, proprietary tumor stroma target identified and characterized by its XPRESIDENT technology platform. COL6A3 exon 6 is presented predominantly by tumor stromal cells and not, or to a far lesser extent, by normal tissues. It is highly prevalent in a broad range of tumor tissues, including pancreatic cancer, breast cancer, gastric cancer, sarcoma, esophageal cancer, non-small cell lung cancer, head & neck squamous cell carcinoma, colorectal cancer, mesothelioma and ovarian cancer, with an estimated 40-80% of such cancers expressing COL6A3 exon 6.

The company focuses its clinical resources on the three IMA203 Phase 1b cohorts, as well as accelerating the clinical development for the PRAME TCER IMA402. Therefore, as announced in November 2022, the company has delayed the IND submission for an ACTengine candidate IMA204.

The company’s manufacturing process is designed to create hundreds of doses from one single donor leukapheresis. Gamma delta T cells are abundant in the peripheral blood, show intrinsic anti-tumor activity, naturally infiltrate solid tumors and do not cause graft-vs-host disease – characteristics that make this cell type well suited for an allogeneic approach. The ACTallo process engineers gamma delta T cells with CARs or TCRs, thus accessing cancer cell surface targets as well as intracellular proteins that are presented as peptides on the surface of the cancer cell. This aims to enable the redirection of gamma delta T cells to cancer cell targets. ACTallo products would be available for patient treatment without the requirement for personalized manufacturing.

The company’s half-life extended TCER molecules are next-generation, antibody-like off-the-shelf biologics that leverage the body’s immune system by redirecting and activating T cells towards cancer cells expressing a specific tumor target.

The company has developed a broad pipeline of next-generation half-life extended TCR Bispecifics with the potential for addressing different indications and large patient populations with an innovative therapeutic option.

TCER IMA401 targeting a MAGEA4/8 peptide presented by HLA-A*02:01 (developed in collaboration with BMS): Start of clinical trial in May 2022, dose escalation ongoing.

TCER IMA402 targeting a PRAME peptide presented by HLA-A*02:01: Start of clinical trial planned for 2H 2023.

TCER IMA403 targeting an undisclosed peptide presented by HLA-A*02:01: Preclinical PoC studies ongoing.

TCER IMA40x comprising several innovative TCER candidates targeting undisclosed peptides presented by HLA-A*02:01 and other HLA-types: TCER engineering and preclinical testing ongoing.

IMA401 is the most advanced product candidate from the company’s TCR Bispecifics pipeline targeting an HLA-A*02:01-presented peptide derived from both MAGEA4 and MAGEA8. The MAGEA4/8 peptide has been identified and validated by its proprietary mass spectrometry-based target discovery platform XPRESIDENT and is presented at a >5-fold higher copy number per tumor cell than a commonly targeted MAGEA4 peptide, and is highly prevalent in several solid tumor types.

In December 2021, the company announced that it entered into a license, development and commercialization agreement for IMA401 with BMS.

The company’s TCER IMA402 is directed against the same peptide derived from PRAME as used for ACTengine IMA203. PRAME is one of the most frequently expressed targets and highly prevalent in several solid tumor types, such as melanoma, uveal melanoma, uterine cancers, ovarian cancer, subtypes of sarcoma, squamous NSCLC, TNBC, head and neck cancer, among other indications.

To characterize the company’s proprietary and partnered product candidates and to identify and develop future TCR-based product candidates, it established two proprietary target and TCR discovery platforms: XPRESIDENT and XCEPTOR.

The company has identified a pool of more than 200 well-known and unknown cancer targets that have the potential for further development of proprietary and partnered assets and allow it to build a unique position in complementary T cell therapies – ACT and TCR Bispecifics- to maximize value generation.

XPRESIDENT integrates a high-throughput, ultra-sensitive mass spectrometry coupled with a proprietary workflow and an immunoinformatics platform. It builds on a primary tissue database of thousands of tissues.

XPRESIDENT has identified and characterized cancer targets for all of the company’s clinical and preclinical programs across its entire individual and partnered pipeline. Each of the company’s pipeline programs is targeting HLA-A*02:01, which is found in approximately 40-50% of individuals in North America and Europe and in approximately 20-35% of individuals in East Asia, and is one of the most common HLA types worldwide.

XCEPTOR is the company’s proprietary, TCR identification platform enabling the discovery and engineering of TCRs with high affinity and specificity.

Manufacturing and Supply

ACTengine

All clinical T cell products are manufactured by the company’s employees through a collaboration with the Evelyn H. Griffin Stem Cell Therapeutics Research Laboratory at UTHealth (UTH) McGovern Medical School in Houston, Texas that provides it exclusive access to three cGMP manufacturing suites and support areas for the manufacturing of its cell products.

Strategy

The company seeks to execute the following strategy to develop TCR-based immunotherapies for the treatment of cancer, maximizing the value of its technology platforms and the broad portfolio of product candidates realize the full multi-cancer opportunity of PRAME; advance its pipeline of innovative ACTengine TCR-T product candidates; advance its pipeline of next-generation, half-life extended TCR Bispecifics; further enhance its cell therapy manufacturing capabilities; develop allogeneic off-the-shelf cell therapies; leverage the full potential of strategic collaborations; strengthen its intellectual property portfolio; enhance the competitive edge of its technology platforms; and realize the full multi-cancer opportunity of PRAME.

Intellectual Property

The company’s intellectual property portfolio includes patents in many commercially significant jurisdictions, such as Europe, the United States, Canada, China, Japan, Australia, and others. For technologies with potential for the highest commercial impact, the company’s patent filing covers more than 50 countries.

As of February 1, 2023, the company’s patent portfolio included more than 115 active patent families and over 5,800 patents and patent applications worldwide. The company owns over 2,400 patents worldwide, including more than 550 U.S. patents. The company plans to continue expanding its U.S. patent portfolio to further strengthen the protection of its lead projects.

At present, IP protection for the company’s product candidates, encompassing proprietary cancer antigen targets, TCRs, TCERs and antibodies, includes the following:

IMA201: Four issued patents in the U.S., fifteen issued foreign patents in Australia (3), South Korea (3), Colombia (2), Morocco (2), Germany, India, Indonesia, Malaysia, New Zealand, Taiwan, South Africa and China; hundred-and-seventy-three (173) pending patent applications in Argentina, Australia, Brazil, Canada, Chile, China, Colombia, Costa Rica, Algeria, Eurasia, Egypt, Europe, Hong Kong, Indonesia, Israel, India, Japan, South Korea, Mexico, Malaysia, Morocco, New Zealand, Peru, the Philippines, Singapore, Thailand, Taiwan, the Ukraine, the U.S., Vietnam and South Africa, as well as 4 International applications (PCT) and 6 US provisional applications relating to IMA201 (MAGEA4/8). These patents and patent applications, if issued, are expected to expire between 2037 and 2042, in each case without taking into account any possible patent term adjustment or extensions and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.

IMA203: Five issued patents in the U.S., four issued foreign patents in Germany (2), Taiwan and Algeria, hundred-and-fifty-eight (158) pending patent applications in Argentina, Australia, Brazil, Canada, Chile, China, Colombia, Costa Rica, Germany, Eurasia, Egypt, Europe, Gulf Cooperation Council, Hong Kong, Indonesia, Israel, India, Japan, South Korea, Mexico, Malaysia, New Zealand, Peru, Philippines, Singapore, Thailand, Taiwan, the Ukraine, the U.S., Vietnam and South Africa as well as 5 International applications (PCT) and 8 US provisional applications relating to IMA203 (PRAME). These patents and patent applications, if issued, are expected to expire between 2038 and 2042 in each case without taking into account any possible patent term adjustment or extensions and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.

IMA204: Seven issued patents in the U.S., ninety-three (93) issued foreign patents in Germany, Japan, Hong Kong, South Korea, Mexico, New Zealand, Taiwan, Algeria, South Africa and Europe (two European patents each validated in 40 countries), hundred-and-eighty-one (181) pending patent applications in Argentina, Australia, Brazil, Canada, Chile, China, Columbia, Costa Rica, Germany, Algeria, Eurasia, Egypt, Europe, Gulf Cooperation Council, Hong Kong, Indonesia, Israel, India, Japan, South Korea , Mexico, Malaysia, New Zealand, Peru, the Philippines, Singapore, Thailand, Taiwan, Tunisia, the Ukraine, the U.S., Vietnam and South Africa, as well as 4 International applications (PCT) and 7 US provisional applications relating to IMA204 (COL6A3 exon 6). These patents and patent applications, if issued, are expected to expire between 2031 and 2042, in each case without taking into account any possible patent term adjustment or extensions and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.

IMA401: Four issued patents in the U.S., eight issued foreign patents in Australia (2), Germany, India, South Korea, Colombia, South Africa and Morocco, two-hundred-and-twelve (212) pending patent applications in Argentina, Australia, Brazil, Canada, Chile, China, Costa Rica, Algeria, Eurasia, Egypt, Europe, Gulf Cooperation Council, Hong Kong, Indonesia, Israel, India, Japan, South Korea, Mexico, Malaysia, New Zealand, Peru, the Philippines, Singapore, Thailand, Taiwan, the Ukraine, the U.S., Vietnam and South Africa, as well as 4 International applications (PCT) and 6 US provisional applications relating to IMA401 (MAGEA4/8). These patents and patent applications, if issued, are expected to expire between 2037 and 2042, in each case without taking into account any possible patent term adjustment or extensions and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees. IMA401 is further protected by a patent family covering the TCER Platform.

IMA402: Five issued patents in the U.S., two issued foreign patents in Taiwan and Algeria, ninety-five (95) pending patent applications in Argentina, Australia, Brazil, Canada, Chile, China, Colombia, Costa Rica, Germany, Eurasia, Egypt, Europe, Gulf Cooperation Council, Hong Kong, Indonesia, Israel, India, Japan, South Korea, Mexico, Malaysia, New Zealand, Peru, the Philippines, Singapore, Thailand, Taiwan, the Ukraine, the U.S., Vietnam and South Africa, as well as 4 International applications (PCT) and 6 US provisional applications relating to the clinical candidates for IMA402 (PRAME). These patents and patent applications, if issued, are expected to expire between 2038 and 2043, in each case without taking into account any possible patent term adjustment or extensions and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees. IMA402 is further protected by a patent family covering the TCER Platform

Further, the company pursues patent protection for different aspects of its ACT technology and methods, which also relate and thus confer protection to the clinical projects, IMA201 to IMA204, IMA401 and IMA402. To this end, the company’s subsidiary, Immatics US, has filed and owns 23 patent families. These patents and patent applications are predominantly focused on ACT methods, cell populations, and other immunotherapy methodologies. If issued, these patents and patent applications are expected to expire between 2038 and 2043, in each case without taking into account any possible patent term adjustment or extensions and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.

The company also places an emphasis on protecting its expanding brand recognition by filing and registering trademark applications throughout the world. The company owns 20 different trademarks, most of which are registered or have been allowed, in multiple countries and trademark product and services classes. Prominent trademarks are, for example, Immatics, XPRESIDENT, TCER, XCEPTOR, ACTallo and ACTengine.

Collaborations and Other Agreements

Editas

In June 2022, the company and Editas entered into a strategic collaboration and licensing agreement to combine its gamma delta T cell adoptive cell therapies with Editas’ CRISPR gene editing technology.

Under the terms of the agreement, Editas Medicine received an undisclosed upfront cash payment and is eligible to receive additional milestone payments based on development, regulatory, and commercial milestones.

Bristol Myers Squibb

In August 2019, the company and Celgene Corporation, a wholly owned subsidiary of BMS, entered into a strategic collaboration and license agreement to develop novel adoptive cell therapies targeting multiple cancers. The company retains certain early stage co-development and co-funding rights for selected TCR-T cell therapies arising from the collaboration.

On June 2, 2022, the company expanded its 2019 collaboration agreement with BMS to include one additional TCR target discovered by Immatics.

On June 2, 2022, Immatics and BMS also entered into a new collaboration to develop allogeneic TCR-T/CAR-T programs, bringing together the company’s allogeneic gamma delta T cell therapy platform ACTallo with BMS’ technologies and oncology drug development expertise. Under this collaboration, the parties will develop two programs owned by BMS and both companies have an option to develop up to four additional programs each. The programs will utilize the company’s proprietary gamma delta T cell-derived, allogeneic ACT platform, called ACTallo, and a suite of next-generation technologies developed by BMS.

On December 10, 2021, the company entered into a License, Development and Commercialization Agreement with BMS relating to its TCR Bispecific candidate, IMA401. Pursuant to the agreement, the company granted to BMS an exclusive, worldwide, sublicensable license to develop, manufacture, and commercialize IMA401 and certain other bispecific and multispecific molecules that bind to a MAGEA4/A8 peptide and engage and activate endogenous T-cells or other immune cells for any diagnostic, prophylactic or therapeutic uses, excluding cell therapy and cell therapy products. BMS granted it a non-exclusive, perpetual, worldwide, sublicensable, royalty-free license to certain BMS Company patents and know-how that are improvements to its platform technology that may be generated by Bristol-Myers Squibb in the performance of activities under the agreement.

GlaxoSmithKline (GSK)

On October 24, 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 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 became effective on December 26, 2022.

Genmab

In July 2018, the company and Genmab entered into a research collaboration and license agreement to develop next-generation, T cell engaging bispecific immunotherapies targeting multiple cancer indications. Under the agreement, it is conducting joint research, funded by Genmab, and combining XPRESIDENT, XCEPTOR and TCER technology platforms with Genmab’s proprietary antibody technologies to develop multiple bispecific immunotherapies in oncology. Effective January 2, 2023 and for strategic reasons, Genmab provided Immatics with notice of its decision to terminate one program under the collaboration. Both the company and Genmab are exclusively discovering and developing immunotherapies directed against two proprietary targets, discovered and developed by its XPRESIDENT platform. Genmab is responsible for development, manufacturing and worldwide commercialization. The company retains an option to contribute certain promotion efforts at predetermined levels in selected countries in the EU.

UTHealth

The company entered into a multi-year collaboration agreement to secure exclusive access to three UTHealth cGMP suites to manufacture various ACT products within the Griffin Research Laboratory. Under the agreement, general facility operations, maintenance, supply and reagents for cGMP manufacture, and co-release of product is provided by UTHealth. Under the agreement, it performs all manufacturing and in-process controls. The UTHealth facility is FDA registered to produce cells and tissues for clinical applications in compliance with cGMP and has received accreditation by the FACT in January 2016, which was renewed in 2019. In August 2020 UTHealth and Immatics extended the collaboration until the end of 2024 providing Immatics exclusive access to cGMP manufacturing infrastructure at The Evelyn H. Griffin Stem Cell Therapeutics Research Laboratory. The extended collaboration ensures continued clinical batch supply for all of Immatics’ ongoing and future ACT clinical trials in the United States and Europe.

MD Anderson Cancer Center

In August 2015, the company and The University of Texas M.D. Anderson Cancer Center (MD Anderson) announced the launch of Immatics US to develop multiple T cell and TCR-based adoptive cellular therapies.

Competition

The company’s competitors fall primarily into the following groups, depending on their treatment approach:

Companies, such as Adaptimmune, Gritstone, Immunocore Limited (Immunocore), Adaptive Biotechnologies, pureMHC, BioNTech (BioNTech RNA Pharmaceuticals GmbH), and Genentech (Genentech, Inc.) are also seeking to identify HLA targets.

Companies, such as Adaptimmune, Affini-T, Kite Pharma (a Gilead (Gilead Sciences, Inc.) company), Tmunity (a Gilead company), T-knife, Juno Therapeutics (a BMS company), 2seventybio, Medigene (MediGene AG), BioNTech, PACT Pharma, T-scan Therapeutics, ImmunoScape, Alaunos Therapeutics are investigating novel autologous TCR-T therapeutics.

Companies, such as Immunocore, Amgen (Amgen Inc., Thousand Oaks/CA/USA), Genmab (Genmab A/S, Copenhagen/Denmark), Eureka Therapeutics, Molecular Partners, Harpoon Therapeutics, MacroGenics, Abbvie and Roche are developing TCR Bispecific compounds or TCR mimetic antibodies.

Companies, such as Immunocore, Eureka Therapeutics, Molecular Partners, CDR-Life, Regeneron and Roche are developing TCR Bispecific compounds or TCR mimetic antibodies.

Trademarks, Service Marks

The Immatics logo, Immatics, XPRESIDENT, ACTengine, ACTallo, ACTolog, XCEPTOR, TCER, AbsQuant, IMADetect and other trademarks or service marks of Immatics.