MAGEA4

BMS is ending its $150m deal with Immatics to help develop its bispecific. Image credit: Getty Images / sesame. Immatics has been left with the full rights to develop a bispecific molecule after its partner Bristol Myers Squibb (BMS) cut ties with the project. BMS has handed back both the development and commercialisation rights for IMA401 to the biopharmaceutical company after a $150m upfront payment in 2021, with an expected $770m in milestone payments. Immatics said the collaboration ended due to an ongoing portfolio prioritisation push by BMS. The announcement comes as Immatics announces Phase I, proof-of-concept data for its T cell receptor (TCR) bispecific, TCER IMA401, at the European Society of Medical Oncology meeting, taking place in Barcelona, Spain, from 13 to 17 September. The Phase Ia dose escalation study (NCT05359445) has enrolled 35 patients with solid tumours across 16 indications who are HLA-A*02:01 and MAGEA4/8-positive and had received a median of four and up to eight lines of prior systemic treatments. See Also: Bicara Therapeutics closes $362m IPO in flurry of biotech listing activity MaxCyte and Kamau Therapeutics sign platform license agreement As of a 23 July 2024 data cutoff, there was an objective response rate (ORR) of 29%, confirmed ORR (cORR) of 25%, disease control rate (DCR) of 53% and tumour shrinkage rate of 53%. Immatics’s chief development officer Dr Carsten Reinhardt said: “We are very pleased to observe initial anti-tumour activity, including durable objective responses, during dose escalation in a heavily pre-treated patient population and across several solid tumour types. “As the clinical trial progresses, our goal will be to further leverage the potential of this product candidate by focusing on the enrolment of indications with high MAGEA4/8 target expression, such as lung and head and neck cancer patients, seeking to optimise the treatment schedule and also exploring the incremental clinical benefit available to patients through combining IMA401 with a checkpoint inhibitor.” IMA401 is a bispecific fusion protein that acts by targeting cells expressing MAGEA4 and MAGEA8, both of which are expressed at higher levels in tumour conditions. Current data supports a two-week dosing schedule but Immatics is hopeful to reduce this to once every four weeks. Immatics also says that IMA401 has a manageable tolerability profile. More data is expected in 2025. Immatics has several other drugs in the pipeline, including IMA402 and IMA203 . Free Whitepaper Optimise your cell therapy process: a guide to cell thawing Typically carried out at the point of care, errors in cell therapy thawing could compromise treatment efficacy, leading to significant patient impact as well as high costs and a compromised reputation for the product’s developer. This guide addresses how cell thawing has historically developed into the new techniques used today, along with the physical and biological implications of key metrics and components such as warming rate and ice structure. Also included are reviews of key studies from scientific literature and a consideration of the interactions between cooling and warming rates, as applicable to cell and gene therapies. Thank you. You will receive an email shortly. Please check your inbox to download the Whitepaper. By Cytiva Thematic By downloading this Whitepaper, you acknowledge that GlobalData may share your information with Cytiva Thematic and that your personal data will be used as described in their Privacy Policy

HOUSTON, TX, USA and TUEBINGEN, Germany I September 16, 2024 I 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, today presented 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) Congress 2024. Initial data from the IMA401 Phase 1a first-in-human dose escalation basket trial in a broad range of heavily pretreated patients with recurrent and/or refractory solid tumors showed initial anti-tumor activity, durable objective responses, including confirmed responses ongoing at 13+ months, and a manageable tolerability profile. The data from the ongoing Phase 1 trial will be presented today by Martin Wermke, M.D. during the Investigational Immunotherapy oral presentation session at the ESMO Congress 2024. The IMA401 data slides are accessible in the ‘ Events & Presentations ’ section of the Investor & Media section of the Company’s website. “Today marks the achievement of a major milestone for Immatics as the data presented confirm clinical proof-of-concept for our proprietary TCER® therapeutic approach and IMA401, our next-generation, half-life extended TCR-based bispecific targeting a novel tumor-specific peptide derived from MAGEA4/8. We are very pleased to observe initial anti-tumor activity, including durable objective responses, during dose escalation in a heavily pre-treated patient population and across several solid tumor types,” said Carsten Reinhardt, M.D., Ph.D., Chief Development Officer at Immatics. “As the clinical trial progresses, our goal will be to further leverage the potential of this product candidate 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.” In addition, the collaboration with Bristol Myers Squibb (NYSE: BMY) for the co-development of IMA401 has ended due to ongoing portfolio prioritization efforts within Bristol Myers Squibb. The existing collaboration and license agreement signed in December 2021 will terminate effective December 12, 2024. Thereafter, all IMA401 development and commercialization rights will be reverted to Immatics. Immatics is not obligated to refund Bristol Myers Squibb any part of the $150 million upfront received under the collaboration and is not required to make any future milestone payments to Bristol Myers Squibb; the parties will engage in a wind-down period as stipulated under the collaboration agreement. Based on the terms of the agreement with Bristol Myers Squibb, Immatics has been responsible for conducting the ongoing Phase 1 clinical trial. Immatics intends to advance IMA401 further through clinical development. The next data update is expected in 2025. “Building on the initial anti-tumor activity observed in heavily pretreated patients with solid tumors, we are delighted to bring this highly promising drug candidate back into our pipeline as a wholly owned asset,” said Harpreet Singh, Ph.D., CEO and Co-Founder of Immatics. “We see tremendous potential in going after cancers that express MAGEA4 and MAGEA8, complementing our PRAME franchise and strengthening our ability to deliver a meaningful impact on the lives of solid cancer patients.” Key Clinical Findings from TCER® IMA401 Monotherapy Phase 1 Trial Patient baseline characteristics: Heavily pretreated patients with a broad range of tumor types As of data cut-off on July 23, 2024, 35 heavily pretreated patients with recurrent and/or refractory solid tumors have been treated with IMA401 monotherapy across nine escalating dose levels. The treated patient population is composed of patients with 16 different solid tumor indications who are 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 have an ECOG performance status of ≥ 1. The safety population includes all 35 patients treated with IMA401. 29 patients were evaluable for efficacy analysis, of which 17 patients were treated at relevant dose and target levels 1 . Safety: Treatment with IMA401 demonstrates a manageable tolerability profile IMA401 demonstrated an overall manageable tolerability profile in the 35 patients treated. The most frequent treatment-related adverse events (AEs) were transient lymphopenia and mild to moderate cytokine release syndrome (CRS) with the majority of CRS occurring at the first dose. Both AEs are consistent with the proposed mechanism of action and reported for other bispecific T cell engagers. Neutropenia was also observed at high dose levels and occurred mostly at the initial target dose in patients with and without dexamethasone pre-medication. High-grade neutropenia was fully resolved in all cases except one. Dose escalation for the trial is ongoing and the maximum tolerated dose has not yet been determined. Pharmacokinetics: Next-generation TCER® format shows extended half-life in solid cancer patients IMA401 demonstrated an “antibody-like” median half-life of over two weeks (16.9 days). This supported the switch to q2w dosing (once every two weeks) during dose escalation. In addition, the data support pursuing increased dosing intervals of up to q4w (once every four weeks), which could further offer an ideal dosing interval for potential combination with checkpoint inhibitors. Initial anti-tumor activity: IMA401 demonstrates initial anti-tumor activity in multiple tumor types As of data cut-off on July 23, 2024, three of four confirmed responses were ongoing at 13+, 8+ and 3+ months. Deep responses (tumor shrinkage of ≥50%) were observed in four patients (head and neck squamous cell carcinoma, neuroendocrine tumor of unknown primary, cutaneous and mucosal melanoma). The data obtained also indicate that objective responses are associated with MAGEA4/8 target expression level. 1 Patients in this analysis had received IMA401 infusions ≥ 1 mg and showed MAGEA4/8 target expression higher than the MAGEA4/8 high qPCR threshold (n=17). About IMA401 TCER® IMA401 is Immatics’ most advanced TCER® molecule from the Bispecifics pipeline that targets an HLA-A*02-presented (human leukocyte antigen) peptide derived from two different cancer-associated proteins, melanoma-associated antigen 4 and/or 8 (“MAGEA4/8”). The MAGEA4/8 peptide has been identified and validated by Immatics’ proprietary mass spectrometry-based target discovery platform XPRESIDENT® and is presented at a 5-fold higher copy number per tumor cell than the MAGEA4 peptide targeted in other clinical trials. TCER® IMA401 is currently being evaluated in a Phase 1 basket trial in patients with solid tumors expressing MAGEA4/8. The MAGEA4/8 peptide has a high prevalence in several solid tumor indications such as head and neck squamous cell carcinoma (HNSCC), small cell lung cancer (SCLC), as well as melanoma, sarcoma subtypes and other solid cancer types. – 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. Immatics intends to use its website www.immatics.com as a means of disclosing material non-public information. For regular updates you can also follow us on X , Instagram and LinkedIn . SOURCE: Immatics

Immatics, which was already responsible for the phase 1 trial, plans to advance IMA401 further through clinical development. Bristol Myers Squibb has jettisoned another cancer candidate in-licensed under its former CEO. Immatics is the latest partner to get a termination notice, leaving it in full control of a bispecific molecule that BMS picked up for $150 million upfront late in 2021.The deal, which featured $770 million in milestones, positioned BMS to collaborate with Immatics on the development of IMA401, a bispecific molecule that simultaneously targets MAGEA4/8 on solid tumors and activates T cells. BMS placed the bet before IMA401 entered the clinic—and has now cut its ties to the candidate just as Immatics shared the first phase 1 dose-escalation data.Immatics said BMS ended the co-development deal because of its ongoing portfolio prioritization push, a statement that is supported by recent updates from the Big Pharma. Since Chris Boerner replaced Giovanni Caforio as CEO late last year, BMS has terminated a deal for Agenus’ TIGIT bispecific antibody, dropped a BCMA bispecific T-cell engager and returned an antibody-drug conjugate to Eisai. BMS paid a combined $650 million upfront for the Agenus and Eisai candidates and only u-turned on its BCMA prospect after filing to run a phase 3 trial. Immatics shared details of BMS’ decision to walk away from another $150 million in upfront fees alongside an early look at clinical data on IMA401. The presentation at the European Society for Medical Oncology (ESMO) Congress 2024 covers data on 35 people with 16 different solid tumors. Patients were both HLA-A*02:01 and MAGEA4/8-positive and had received a median of four prior lines of systemic treatments. Immatics studied IMA401 at nine escalating dose levels.In the 29 people who were evaluable for efficacy, Immatics reported four confirmed objective responses. All four responses were in patients who received at least 1 mg of IMA401 and had high MAGEA4/8 levels. The response rate of 14% in the overall efficacy population rose to 25% in the subgroup defined by levels of IMA401 and MAGEA4/8. Transient lymphopenia and mild to moderate cytokine release syndrome (CRS), typically after the first dose, were the most common treatment-related adverse events. In an earlier cut of the data included in the ESMO abstract, Immatics reported up to grade 4 lymphopenia but only grade 1 and 2 CRS. Grade 3/4 neutropenia, low levels of a white blood cell, didn’t reoccur after the introduction of dexamethasone.Immatics, which was already responsible for the phase 1 trial, plans to advance IMA401 further through clinical development. Having switched from dosing every week to every two weeks after seeing clinical data, the biotech believes dosing every four weeks may be possible. Immatics said a four-week schedule would be ideal for potential combinations with checkpoint inhibitors. Updated data are due next year.