Immatics US, Inc.

Houston, Texas and Tuebingen, Germany, August 23, 2022 – Immatics N.V. (NASDAQ: IMTX, “Immatics”), a clinical-stage biopharmaceutical company active in the discovery and development of T cell-redirecting cancer immunotherapies, today announced the treatment of the first patient in its Phase 1b expansion cohort C (NCT03686124) evaluating IMA203CD8, the company’s 2nd generation TCR-T monotherapy approach where a proprietary CD8αβ co-receptor is added to PRAME-specific IMA203 T cells. The CD8 co-receptor plays an important role during T cell antigen recognition and T cell activation, enabling the effective engagement of CD8 and CD4 T cells in the anti-tumor response. The 2nd generation TCR-T IMA203CD8 aims to further enhance depth and durability of anti-tumor responses and clinical outcomes of TCR-T targeting PRAME in patients with solid cancers. PRAME is highly prevalent across several indications thereby supporting the program’s potential to reach a broad patient population. “IMA203CD8’s unique mode of action has been validated by preclinical data presented at SITC last year, which demonstrated sustained suppression of tumor growth in serial killing experiments. With the initiation of the IMA203CD8 cohort, we can now test to what extent the interplay of engineered CD8 and CD4 T cells enhances anti-tumor activity in the clinical setting,” said Dr. Cedrik Britten, M.D., Chief Medical Officer at Immatics. “Today’s milestone brings us closer to our goal of achieving long-lasting responses for a broad range of cancer patients having solid tumors that express PRAME.” The importance of CD4 T cells for the duration of responses has been demonstrated by Immatics in preclinical assays where IMA203CD8 showed enhanced potency and prolonged anti-tumor activity compared to IMA203 alone. These findings are in line with a growing body of literature from CD19 CAR-T cells in hematological cancers that suggest a relevant role of engineered CD4 T cells in maintaining durable anti-tumor responses over a long period. Immatics’ proprietary lentiviral vector enables CD4 and CD8 T cells to be engineered with the PRAME-specific IMA203 TCR and a CD8αβ construct. In the preclinical studies, this approach showed functional superiority over multiple other CD8 constructs in conjunction with the PRAME-specific IMA203 TCR. Immatics has successfully developed a proprietary 4-in-1 vector that includes both IMA203 TCRα and TCRβ as well as CD8α and CD8β chains while maintaining a high transduction rate, circumventing the challenges associated with increasing the lentiviral vector payload. The IMA203CD8 Phase 1b dose expansion cohort is expected to enroll up to 24 patients with different types of solid tumors across several clinical trial sites in the U.S. and in Germany. Following personalized manufacturing and lymphodepletion, patients will receive a single dose of IMA203CD8. Initially, 3 patients will be treated at a dose level 3 (DL3, up to 0.48 billion total transduced T cells per m² body surface area) before patient treatment at the provisional recommended Phase 2 dose, DL4 (up to 1.2 billion total transduced cells per m² body surface area). The primary objective of this Phase 1b cohort is to evaluate the safety profile of IMA203CD8. Secondary objectives include evaluating initial anti-tumor and biological activity. The 2nd generation TCR-T IMA203CD8 is part of Immatics’ strategy to realize the full clinical potential of IMA203 TCR-T targeting PRAME. This strategy includes three Phase 1b expansion cohorts, which have all been initiated during the first half of 2022 and build on the promising early clinical results during the company’s Phase 1a trial. Interim data showed a 50% objective response rate (8/16 patients) across several solid tumor indications including melanoma, head and neck cancer, uveal melanoma and synovial sarcoma. Cohort A – IMA203 as monotherapy at the provisional, recommended Phase 2 dose (RP2D) plus exploration of a higher dose level DL5 (up to 4.7 billion transduced CD8 T cells per m² body surface area) Cohort B – IMA203 in combination with an immune checkpoint inhibitor, Opdivo® (nivolumab) Cohort C – IMA203CD8, a 2nd generation monotherapy in which IMA203 is co-transduced with a CD8 co-receptor Each Phase 1b expansion cohort is designed to evaluate the observed objective response rate, demonstrate durability of response and provide the basis for entering registration trials. The next data readout for the IMA203 monotherapy cohort at RP2D is expected during 2H 2022 and an initial data readout for Cohort B and Cohort C is planned for YE2022. About IMA203CD8 and target PRAME ACTengine® IMA203CD8 T cells are 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 programs’ 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®. Through its proprietary TCR discovery and engineering platform XCEPTOR®, Immatics has generated a highly specific T cell receptor (TCR) against this target which is engineered into CD8 and CD4 T cells alongside a proprietary CD8αβ co-receptor for its 2nd generation TCR-based cell therapy approach, ACTengine® IMA203CD8. In preclinical studies, Immatics’ proprietary CD8αβ construct showed functional superiority over multiple other CD8 constructs in conjunction with the PRAME-specific IMA203 TCR. About ACTengine® ACTengine® is a personalized cell therapy approach for patients with advanced solid tumors. The patient’s own T cells are genetically engineered to express a novel, proprietary TCR directed against a defined cancer target. The modified T cells are then reinfused into the patient to attack the tumor. The approach is also known as TCR-engineered cell therapy (TCR-T). All Immatics’ ACTengine® product candidates can be rapidly manufactured utilizing a proprietary manufacturing process designed to enhance T cell engraftment and persistence in vivo. The ACTengine® T cell products are manufactured at the Evelyn H. Griffin Stem Cell Therapeutics Research Laboratory in collaboration with UTHealth. - END - About Immatics Immatics combines the discovery of true targets for cancer immunotherapies with the development of the right T cell receptors with the goal of enabling a robust and specific T cell response against these targets. This deep know-how is the foundation for our pipeline of Adoptive Cell Therapies and TCR Bispecifics as well as our partnerships with global leaders in the pharmaceutical industry. We are committed to delivering the power of T cells and to unlocking new avenues for patients in their fight against cancer. For regular updates about Immatics, visit www.immatics.com. You can also follow us on Instagram, Twitter and LinkedIn.

October 7, 2015 By Mark Terry , BioSpace.com Breaking News Staff MD Anderson Cancer Center , located in Houston, Texas, announced yesterday that together with Seattle-based Theraclone Sciences, Inc. , it was launching an immuno-oncology antibody discovery company, OncoResponse . In addition, OncoResponse closed a Series A financing round worth $9.5 million, co-led by ARCH Venture Partners , Canaan Partners and MD Anderson . Also participating were William Marsh Rice University and Alexandria Real Estate Equities . The startup will utilize Theraclone ’s I-STAR immune screening platform to identify potential therapeutic antibodies against novel targets culled from immuno-oncology patients. This technology screens antibodies produced by the human body in order to identify those that have particular sensitivity and reactivity that might be useful for cancer drugs. MD Anderson will provide samples from willing patients, as well as clinical data in patients that respond well to therapies. If any of OncoResponse ’s products make it to clinical trials, they will be performed at MD Anderson . “The immune system of patients who have responded exceptionally well to cancer immunotherapies may hold the key within their memory repertoire as to what gives them an edge over other patients with less robust immune responses,” said Clifford Stocks , chief executive officer of Theraclone and interim chief executive officer of OncoResponse in a statement. “It could provide us with a way to increase success rates in treating cancer. I-STAR immune repertoire screening technology has the unique capability to identify rare cancer-fighting antibodies and new targets. We’re extremely excited to have teamed up with MD Anderson experts to make a difference in the lives of patients with cancer and their families.” In April, Theraclone announced that it was using its human memory B-cell interrogation platform, in other words I-STAR, to identify possible therapeutic antibodies against the Ebola virus. That project is part of a consortium formed by Seattle-based BIO Ventures for Global Health , along with a number of Ebola experts. Theraclone received up to $4.4 million in a Series C financing round, including an investment from the Wellcome Trust . MD Anderson has been active in biotech-related company development recently. On Aug. 26, The University of Texas MD Anderson Cancer Center inked a deal with Germany-based Immatics Biotechnologies GmbH to launch Immatics US Inc. This company will develop adoptive cellular therapies (ACT) to treat a variety of cancer. Immatics US launched with $60 million, of which $40 million came from Immatics Biotechnologies and $19.7 million came from grants from the Cancer Prevention and Research Institute of Texas . MD Anderson , also in August, formed an alliance with Esperance Pharmaceuticals, Inc. to push development of its lead anti-cancer candidate EP-100 for ovarian cancer. It also penned a deal with Merck & Co. to evaluate anti-PD-1 therapy Keytruda in combination with other drugs and cancer treatments. Immuno-oncology is the hot new area for cancer treatment. At its most basic, it programs the patient’s immune system to attack specific cancer cells. There has also been significant work on so-called checkpoint inhibitors. Cancer cells create molecules that prevent the body’s immune system from working effectively. By stimulating and programming immune cells while simultaneously blocking the tumor cell’s ability to put the brakes on the immune system, immuno-oncology is showing great promise and is the focus of a lot of research. Companies making headway in this area include AstraZeneca PLC , MedImmune , Sanofi and Regeneron Pharmaceuticals, Inc. . Regeneron Pharmaceuticals, Inc. and Roche , and Roche , to name just a few. “The field of immuno-oncology has shown the potential to dramatically improve outcomes for patients with certain types of cancer,” said George Yancopoulos , chief scientific officer of Regeneron and president of Regeneron Laboratories in a July 2015 statement regarding a collaboration with Sanofi . “However, the field is still in its very early days. We believe the approaches most likely to deliver the best results to patients will combine multiple innovative therapies acting on different pathways and targets both in the tumor and the body’s immune response—and will precisely target these medicines to the right patient.” MD Anderson and Theraclone ’s spinoff, OncoResponse , will have headquarters in Houston. It is reportedly hiring five to 10 employees.

August 26, 2015 By Alex Keown , BioSpace.com Breaking News Staff HOUSTON -- The University of Texas MD Anderson Cancer Center teamed up with Germany-based Immatics Biotechnologies GmbH to launch Immatics US Inc. , which is aimed at developing adoptive cellular therapies (ACT) for the treatment of a number of cancers. Immatics US will launch with a war chest of more than $60 million, which includes $40 million from Immatics Biotechnologies and $19.7 million in grant money from the Cancer Prevention and Research Institute of Texas . The new company will be led by Hapreet Singh , the co-founder of Immatics Biotechnologies . Using the technologies at its disposal, Singh said Immatics has “discovered dozens of novel immunotherapy targets” for the company to explore. “With several complementary development programs guided by some of the most exceptional scientists in the field of cancer immunotherapy, we are in exactly the right place to deliver transforming therapies to cancer patients with high medical need,” Singh said in a statement. In addition to Singh, company leaders include Steffen Walter , who will be the chief scientific officer, Toni Weinschenk , chief technology officer, and Carsten Reinhardt chief medical officer. There was no indication of how many other employees Immatics U.S. would employ or already has employed. MD Anderson has a history of forming alliances with large pharmaceutical companies. Earlier this month MD Anderson announced an alliance with Esperance Pharmaceuticals, Inc. to accelerate the clinical development of its lead anti-cancer candidate EP-100 for the treatment of ovarian cancer. Additionally, MD Anderson struck a deal with Merck & Co. to evaluate its blockbuster anti-PD-1 therapy Keytruda in combination with other treatments, such as chemotherapy, radiation therapy and other antitumor medicines. Immatics U.S. will capitalize on its parent company’s technology platform XPRESIDENT for the “discovery and further qualification” of “highly specific cancer targets that can be used as the basis for a range of cancer immunotherapy applications including ACT.” The new company will develop three different ACT approaches for the treatment of tumors with high un-met medical needs, the first of which will enter the clinic in 2016. The three approaches include ACTolog, ACTengine and ACTallo. The ACTolog process involves selecting, enriching and the ex-vivo expansion of a patient’s endogenous T cells specifically recognizing Immatics’ XPRESIDENT targets. ACTengine involves genetically engineering a patient’s own T cells to express novel T-cell receptors which are specific to Immatics’ XPRESIDENT targets, the company said. ACTallo is an allogenic approach that will use off-the-shelf T cells that have been engineered to express novel T-cell receptors. Immatics US, Inc. will develop both autologous and allogenic ACT approaches by capitalizing on MD Anderson ‘s clinical oncology and cell therapy programs and Immatics’ cancer target and T-cell receptor (TCR) discovery capabilities, the new company said in a statement this morning. The new company will use MD Anderson ’s cytokine IL-21 for expansion of T cells, which is a gamma-delta T-cell platform for allogeneic cell therapy approaches and various technologies designed to optimize the development of ACT. “This capability will enable Immatics US, Inc. to develop TCR-based approaches and to have complementary utility with other approaches for addressing tumor targets. Immatics believes its ACT will be both efficacious and safe due to the specificity of its novel well-characterized targets, including novel over-expressed, cancer-testis and neo-antigens ideally suited for specific and safe ACT approaches,” the company said in a statement.