On March 27, 2025 Tyra Biosciences, Inc. (Nasdaq: TYRA), a clinical-stage biotechnology company focused on developing next-generation precision medicines that target large opportunities in Fibroblast Growth Factor Receptor (FGFR) biology, reported financial results for the fourth quarter and full year ended December 31, 2024, and highlighted recent corporate progress (Press release, Tyra Biosciences, MAR 27, 2025, View Source [SID1234651541]).

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"2024 was a momentous year for TYRA and the patient communities we serve, highlighted by the positive interim results from our SURF301 study, which demonstrated a combination of high anti-tumor activity with favorable tolerability results in very sick, heavily pre-treated cancer patients. Importantly, the oncology doses tested in SURF301 are significantly higher than those to be tested in BEACH301, giving us confidence as we advance TYRA-300 in ACH," said Todd Harris, CEO of TYRA. "Our conviction in TYRA-300 has never been stronger and we are working diligently to advance this potential best-in-class agent for multiple high-value indications in oncology and skeletal dysplasia into three Phase 2 studies in NMIBC, ACH and mUC."

Fourth Quarter and Full Year 2024 and Recent Corporate Highlights

TYRA-300

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Advanced Clinical Evaluation of TYRA-300 into Three Phase 2 Studies. During 2024, TYRA progressed TYRA-300, an oral, investigational FGFR3-selective inhibitor, for the treatment of IR NMIBC, mUC and ACH, and achieved the following milestones:
o
Cleared Phase 2 NMIBC IND with US FDA – SURF302. TYRA expanded the clinical development of TYRA-300 into NMIBC to address the unmet needs in this cancer population for an efficacious, orally available therapy. SURF302 is an open-label Phase 2 clinical study evaluating the efficacy and safety of TYRA-300 in participants with FGFR3-altered low-grade, IR NMIBC. The study will enroll up to 90 participants at multiple sites primarily in the United States. Participants will be randomized initially to treatment with TYRA-300 at 50 mg once-daily (QD) (Cohort 1) or treatment with TYRA-300 at 60 mg QD (Cohort 2). Following a review of efficacy and safety, an additional dosing cohort may be evaluated. The primary endpoint is complete response (CR) rate at three months. Secondary endpoints include time to recurrence, the median duration of response, recurrence free survival (RFS), progression free survival (PFS), safety and tolerability.
o
Cleared Phase 2 ACH IND with US FDA – BEACH301. The study is a Phase 2, multicenter, open-label, dose-escalation/dose-expansion study evaluating TYRA-300 in children ages 3 to 10 with achondroplasia with open growth plates. The study will enroll children who are treatment-naïve (Cohort 1) and those who have received prior growth-accelerating therapy (Cohort 2) at multiple sites across the globe. Each of these cohorts is expected to enroll up to 10 participants per dose level (0.125, 0.25, 0.375, 0.50 mg/kg) for up to 12 months. The study will initially enroll a safety sentinel cohort of up to 3 treatment-naïve participants per dose level in children ages 5 to 10.

o
Reported Interim Clinical Proof-of-Concept Results in mUC Patients – SURF301. TYRA-300 demonstrated encouraging preliminary anti-tumor activity in a heavily pre-treated population: at ≥ 90 mg QD, 6 out of 11 (54.5%) patients with FGFR3+ mUC achieved a confirmed partial response (PR), with 100% disease control rate and sustained duration of activity; positive safety results were reported across all QD doses, with infrequent FGFR2/FGFR1-associated toxicities (data cutoff of August 15, 2024). TYRA-300 is being evaluated in Part B of SURF301 (NCT05544552) at potentially therapeutic QD doses in preparation for potential future Phase 2 studies.

TYRA-200

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Advanced Phase 1 SURF201 Study. TYRA-200 is an FGFR1/2/3 inhibitor with potency against activating FGFR2 gene alterations and resistance mutations. SURF201 (Study in PrevioUsly treated and Resistant FGFR2+ Cholangiocarcinoma and Other Advanced Solid Tumors) (NCT06160752) is a multi-center, open label study designed to evaluate the safety, tolerability, and pharmacokinetics of TYRA-200 and determine the optimal and maximum tolerated dose and recommended Phase 2 dose, as well as evaluate the preliminary antitumor activity of TYRA-200. The SURF201 study is currently enrolling and dosing adults with unresectable locally advanced/metastatic intrahepatic cholangiocarcinoma and other advanced solid tumors with activating FGFR2 gene alterations.

TYRA-430

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Cleared Phase 1 IND with US FDA – SURF431. TYRA-430 is an oral, investigational FGFR4/3-biased inhibitor for FGF19+/FGFR4-driven cancers. The Phase 1 study will be a multicenter, open-label, first-in-human study of TYRA-430 in advanced hepatocellular carcinoma (HCC) and other solid tumors with activating FGF/FGFR pathway aberrations (SURF431). We believe TYRA-430 has the potential to address a significant unmet need in HCC, where there are no approved biomarker-driven, targeted therapies.

Corporate

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Strengthened Leadership Team and Board of Directors. In 2024, TYRA appointed Doug Warner, MD, as Chief Medical Officer, and Erik Goluboff, MD, as SVP, Clinical Development to lead the Company’s oncology strategy and clinical development plans. In 2025, TYRA appointed accomplished drug developer Adele Gulfo to its Board of Directors, Sinette Heys as SVP, Clinical Operations to lead the Company’s clinical operations team, and Will Charlton, MD, as SVP, Clinical Development to lead the Company’s skeletal dysplasia clinical development group.

SNÅP Platform and Pipeline

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TYRA continued to advance its in-house precision medicine discovery engine, SNÅP, to develop therapies in targeted oncology and genetically defined conditions.

Fourth Quarter and Full-Year 2024 Financial Results

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Cash, Cash Equivalents and Short-Term Investments. As of December 31, 2024, TYRA had cash, cash equivalents, and marketable securities of $341.4 million, compared to $203.5 million at the end of 2023. The increase was primarily due to the completion of a private placement financing for net proceeds of $199.6 million in the first quarter of 2024. The Company’s current cash, cash equivalents and marketable securities are expected to allow TYRA to execute on its plans through at least 2027.
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Research and Development (R&D) Expenses. Research and development expenses for the three months ended December 31, 2024 were $22.2 million compared to $20.7 million for the same period in 2023, and $80.1 million for the full year 2024 compared to $62.5 million for the same period in 2023. The increases were primarily driven by increased expenses incurred in connection with our ongoing and planned clinical trials and personnel-related costs, including stock-based compensation, partially offset by decreased drug manufacturing and preclinical costs.
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General and Administrative (G&A) Expenses. General and administrative expenses for the three months ended December 31, 2024 were $7.6 million compared to $5.0 million for the same period in 2023, and $24.1 million

for the full year 2024 compared to $17.4 million for the same period in 2023. The increases were primarily driven by increased personnel-related costs, including stock-based compensation.
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Net Loss. Fourth quarter 2024 net loss was $25.6 million compared to $22.8 million for the same period in 2023, and $86.5 million for the full year 2024 compared to $69.1 million for the same period in 2023.

Upcoming Anticipated Milestones and Events

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BEACH301: dose first child with achondroplasia with TYRA-300 – Q2 2025
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SURF302: dose first NMIBC patient with TYRA-300 – Q2 2025
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SURF431: dose first HCC patient with TYRA-430 – Q2 2025

About TYRA-300

TYRA-300 is the Company’s lead precision medicine program stemming from its in-house SNÅP platform. TYRA-300 is an investigational, oral, FGFR3-selective inhibitor currently in development for the treatment of cancer and skeletal dysplasia, including achondroplasia and hypochondroplasia. In oncology, TYRA-300 is being evaluated in mUC and IR NMIBC. In mUC, TYRA-300 is being evaluated in a multi-center, open label Phase 1/2 clinical study, SURF301 (Study in Untreated and Resistant FGFR3+ Advanced Solid Tumors) (NCT05544552). The study is designed to determine the optimal and the recommended Phase 2 dose of TYRA-300, as well as to evaluate the preliminary antitumor activity of TYRA-300. In October 2024, TYRA reported interim clinical proof-of-concept data in mUC from SURF301. TYRA has received IND clearance from the US FDA to proceed with its SURF302 clinical trial in patients with IR NMIBC. In skeletal dysplasia, TYRA-300 has demonstrated positive preclinical results in achondroplasia and hypochondroplasia, and its BEACH301 clinical trial in children with achondroplasia is now recruiting.

About TYRA-200

TYRA-200 is an oral, investigational, FGFR1/2/3 inhibitor with potency against activating FGFR2 gene alterations and resistance mutations. The Phase 1 clinical study of TYRA-200, SURF201 (Study in PrevioUsly treated and Resistant FGFR2+ Cholangiocarcinoma and Other Advanced Solid Tumors) (NCT06160752), is a multi-center, open label study designed to evaluate the maximum tolerated dose (MTD) and the recommended Phase 2 dose of TYRA-200, as well as to evaluate the preliminary antitumor activity of TYRA-200. SURF201 is currently enrolling and dosing adults with advanced/metastatic intrahepatic cholangiocarcinoma and other advanced solid tumors with activating alterations in FGFR2.

About TYRA-430

TYRA-430 is an oral, investigational FGFR4/3-biased inhibitor for FGF19+/FGFR4-driven cancers. The US FDA has cleared Tyra’s IND to proceed with a Phase 1 clinical study of TYRA-430. The Phase 1 study will be a multicenter, open-label, first-in-human study of TYRA-430 in advanced HCC and other solid tumors with activating FGF/FGFR pathway aberrations (SURF431).

On March 27, 2025 Plus Therapeutics, Inc. (Nasdaq: PSTV) (the "Company"), a clinical-stage pharmaceutical company developing targeted radiotherapeutics with advanced platform technologies for central nervous system (CNS) cancers, reported financial results for the fourth quarter and full year ended December 31, 2024, and provides an overview of recent and upcoming business highlights (Press release, Plus Therapeutics, MAR 27, 2025, View Source [SID1234651521]).

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"Over the last twelve months, Plus has reported very promising safety and efficacy data for our lead drug REYOBIQ administered in our two most advanced CNS cancer programs," said Marc H. Hedrick, M.D., Plus Therapeutics President and Chief Executive Officer. "The recently raised capital, coupled with existing grant support, enables us to progress both our therapeutic programs to key clinical and regulatory milestones as well as commercially launch our CNSide diagnostic platform. The year 2025 has the potential to be transformational at Plus as we anticipate transitioning to an operational revenue generating company with the launch of CNSide. We are highly appreciative of our investors, partners and other stakeholders for their continued commitment to Plus as we deliver on our objectives and drive value."

Q4 2024 & RECENT HIGHLIGHTS AND MILESTONES

Corporate

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Raised $15.0 million in a private placement financing, enabling the Company to regain compliance with Nasdaq minimum stockholders’ equity requirement and extending runway into 2026
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Obtained a $2.0 million grant award advance from the Company’s existing $17.6 million grant from the Cancer Prevention and Research Institute of Texas (CPRIT) to accelerate the development of REYOBIQ for our leptomeningeal metastases (LM) program
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Strengthened management team with key leadership appointments:
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Dr. Michael Rosol as Chief Development Officer – Dr. Rosol will lead the Company’s clinical, pre-clinical, and biomarker development activities
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Mr. Russell Bradley as President and General Manager of Plus Therapeutics’ wholly owned subsidiary, CNSide Diagnostics, LLC ("CNSide Diagnostics") – Mr. Bradley will provide leadership at CNSide with an immediate focus on commercialization of the diagnostic platform
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Dr. Jonathan Stein as Medical Director, CNSide Diagnostics – Dr. Stein will provide technical leadership to support CNSide Diagnostics, having experience in all aspects of diagnostic operations, compliance and regulatory affairs

REYOBIQ

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Received U.S. FDA agreement for the brand name REYOBIQ (Rhenium Re186 Obisbemeda) for the Company’s lead radiotherapeutic
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Published Phase 1 clinical trial results for REYOBIQ in the peer-reviewed publication Nature Communications, demonstrating safety and potential efficacy in treating recurrent glioblastoma (GBM), with patients receiving a radiation dose >100 Gy achieving a median overall survival of 17 months, more than double the standard of care. Additional details can be found here
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Granted U.S. FDA Orphan Drug Designation for REYOBIQ for the treatment of LM in patients with lung cancer

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Completed ReSPECT-LM Phase 1 single dose administration trial and determined the maximum feasible and recommended Phase 2 doses. Additional details can be found here
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Presented positive ReSPECT-LM Phase 1 interim data for LM at the 2024 SNO Annual Conference. Additional details can be found here
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Presented positive ReSPECT-LM Phase 1 interim data for breast cancer patients with LM at the 2024 San Antonio Breast Cancer Symposium. Additional details can be found here
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Expanded strategic agreement with Telix IsoTherapeutics Group, securing a reliable supply of cGMP Rhenium-186 for late-stage clinical trials and future commercialization of REYOBIQ. Additional details can be found here

CNSide

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Presented positive FORESEE clinical trial summary demonstrating utility of the CNSide Cerebrospinal Fluid Assay Platform ("CNSide") in diagnosis and clinical management of patients with LM. Additional details can be found here
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Presented real world, multi-institutional, longitudinal data showing the commercial utility of CNSide at the 2024 Society for Neuro-Oncology Annual Meeting. Additional details can be found here

UPCOMING EXPECTED EVENTS AND MILESTONES

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Full commercial launch of CNSide on track for 2025
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Presentations planned for the following upcoming medical conferences:
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Nuclear Medicine and Neuro-oncology Symposium (NMN) in Vienna, Austria (May 9-10, 2025); Title: "Diagnostic and Therapeutic Innovations in the Era of Precision Medicine – Nuclear Medicine Meets Neuro-Oncology" on May 9, 2025 by Dr. Andrew Brenner, M.D, Ph.D.
o
Society for Neuro-Oncology/American Society of Clinical Oncology (SNO/ASCO) CNS Metastases Conference in Baltimore, Maryland (August 14-16, 2025): Corporate Key Opinion Leader symposium, title to be determined
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Complete enrollment of Cohort 1 in the ReSPECT-LM Phase 1 multiple dose administration trial in 2025
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Complete end of Phase 1 meeting with the U.S. FDA for the ReSPECT-LM trial and determine next clinical steps in 2025
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Complete ReSPECT-GBM Phase 2 enrollment in 2025
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Obtain IND approval for the ReSPECT-PBC Phase 1/2 trial of REYOBIQ for pediatric ependymoma and high-grade glioma in H2 2025

FULL YEAR 2024 FINANCIAL RESULTS

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The Company’s cash and investments balance was $3.6 million at December 31, 2024 compared to $8.6 million at December 31, 2023.
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The Company recognized $5.8 million in grant revenue in the year ending December 31, 2024 and $4.9 million for the year ending December 31, 2023, which in both periods represents CPRIT’s share of the costs incurred for REYOBIQ development for the treatment of patients with LM
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Total operating loss for the year ending December 31, 2024 was $14.7 million versus $13.3 million for the year ending December 31, 2023. The increase is primarily due to increased expenditures related to the ReSPECT-LM trial

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Net loss for the year ending December 31, 2024 was $13.0 million, or $(1.95) per basic share versus $13.3 million, or $(4.24) per basic share, for the year ending December 31, 2023
FOURTH QUARTER & FULL YEAR 2024 RESULTS CONFERENCE CALL

The Company will hold a conference call and live audio webcast at 5:00 pm Eastern Time today to discuss its financial results and provide a general business update.

The live audio webcast will be available at ir.plustherapeutics.com/events.

Participants may also pre-register any time before the call here. Once registration is completed, participants will be provided a dial-in number with a personalized conference code to access the call. Please dial in 15 minutes prior to the start time.

Following the live call, a replay will be available on the Company’s website under the ‘For Investors’ section. The webcast will be available on the Company’s website for 90 days following the live call.

On March 27, 2025 Genmab A/S (Nasdaq: GMAB) reported that the Japan Ministry of Health, Labour and Welfare has approved TIVDAK (tisotumab vedotin) for the treatment of advanced or recurrent cervical cancer that has progressed on or after cancer chemotherapy (Press release, Genmab, MAR 27, 2025, View Source [SID1234651522]). TIVDAK is the first and only ADC to be approved for people living with cervical cancer in Japan.

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In recent years, cervical cancer incidence and mortality rates have increased in Japan, particularly among women under age 50.i,ii,iii Moreover, patients with recurrent or metastatic cervical cancer whose disease has progressed after first-line therapy have limited treatment options.

"Patients with advanced or recurrent cervical cancer, in general, have a poor prognosis. The advent of new treatment options, especially for second-line or later treatment, is much needed," said Aikou Okamoto, M.D., Ph.D., Chief Professor, Department of Obstetrics and Gynecology at The Jikei University School of Medicine. "Cervical cancer treatment has advanced in recent years, but it is very meaningful that the approval of tisotumab vedotin as an ADC has increased the number of treatment options with a new mechanism of action that is expected to prolong overall survival. This is good news for patients and healthcare professionals."

The approval is based on data from the randomized, open-label, global Phase 3 innovaTV 301 clinical trial that evaluated the efficacy and safety of TIVDAK compared to chemotherapy in patients with advanced or recurrent cervical cancer who were previously treated with chemotherapy. The trial included 502 patients, 101 of which were Japanese. The trial met its primary endpoint of overall survival (OS), demonstrating a 30% reduction in risk of death (HR: 0.70 [95% CI: 0.54-0.89], two-sided p=0.0038) compared to chemotherapy. Median OS was 11.5 months [95% CI: 9.8-14.9] among patients treated with TIVDAK compared to 9.5 months [95% CI: 7.9-10.7] for patients who received chemotherapy. Secondary endpoints of progression-free survival (PFS) and confirmed objective response rate (ORR) were also met.

Adverse drug reactions occurred in 219 (87.6%) of 250 patients (including 50 Japanese patients) treated with TIVDAK. The most common (≥20%) adverse reactions included conjunctivitis (n=76; 30.4%), nausea (n=73; 29.2%), peripheral sensory neuropathy (n=67; 26.8%), alopecia (n=61; 24.4%), and epistaxis (n=57; 22.8%), at the data cutoff date of July 24, 2023.

"As a company, we understand the urgent need for patients with advanced cervical cancer whose disease has progressed," said Judith Klimovsky, M.D., Executive Vice President and Chief Development Officer of Genmab. "This approval marks an important step forward in transforming the treatment paradigm in Japan, ultimately bringing new hope and possibility to patients and their loved ones."

About the innovaTV 301 Trial
The innovaTV 301 trial (NCT04697628) is a global, 1:1 randomized, open-label Phase 3 trial evaluating tisotumab vedotin versus investigator’s choice of single agent chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan or pemetrexed) in 502 patients with recurrent or metastatic cervical cancer who received one or two prior systemic regimens in the recurrent or metastatic setting.

Patients with recurrent or metastatic cervical cancer with squamous cell, adenocarcinoma or adenosquamous histology, and disease progression during or after treatment with chemotherapy doublet +/- bevacizumab and an anti-PD-(L)1 agent (if eligible) are included. The primary endpoint was overall survival. The main secondary outcomes were progression-free survival and objective response rate.

The study was conducted by Seagen, which was acquired by Pfizer in December 2023, in collaboration with Genmab, European Network of Gynaecological Oncological Trial Groups (ENGOT, study number ENGOT cx-12) and the Gynecologic Oncology Group (GOG) Foundation (study number GOG 3057), as well as other global gynecological oncology cooperative groups. For more information about the Phase 3 innovaTV 301 clinical trial and other clinical trials with tisotumab vedotin, please visit www.clinicaltrials.gov.

About Tisotumab Vedotin
Tisotumab vedotin (approved under the brand name TIVDAK in the U.S. and Japan) is an antibody-drug conjugate (ADC) composed of Genmab’s human monoclonal antibody directed to tissue factor (TF) and Pfizer’s ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody. Nonclinical data suggest that the anticancer activity of tisotumab vedotin is due to the binding of the ADC to TF-expressing cancer cells, followed by internalization of the ADC-TF complex and release of MMAE via proteolytic cleavage. MMAE disrupts the microtubule network of actively dividing cells, leading to cell cycle arrest and apoptotic cell death. In vitro, tisotumab vedotin also mediates antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity.

On March 27, 2025 Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of cancer, reported its financial results for 2024, and provides an update on its product pipeline and outlook for 2025 (Press release, Transgene, MAR 27, 2025, View Source [SID1234651543]).

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"By demonstrating clinical proof of principle for TG4050, Transgene’s first individualized therapeutic cancer vaccine derived from the myvac platform, we achieved a significant milestone in 2024. The highly encouraging early results from the Phase I part of our Phase I/II trial of TG4050 presented at SITC (Free SITC Whitepaper) 2024 have enabled the initiation of the ongoing Phase II part of the study. Enrollment is progressing well, reflecting strong support from both patients and clinicians for this novel candidate. We are confident that this Phase II trial will allow us to further confirm our promising initial data. We are monitoring innovation in the adjuvant setting of operable head and neck cancer and assessing the potential next steps to further accelerate our program."

"In 2025, we will continue to expand the potential of myvac. Our goal is to launch at least one new clinical trial in a second indication by year-end and continue optimizing our design and manufacturing processes. This innovative platform leverages the power of the MVA vector, the latest innovations in AI-powered neoantigen prediction and our strong bioengineering environment to design to design a tailored therapy for each patient and allows us to take advantage of the current momentum in individualized cancer vaccines."

"Driven by these technology advancements and supported by an innovation-driven team, we remain committed to executing our growth strategy. We are confident that our focus on viral vector-based immunotherapies will enable us to deliver transformative benefits to a broad spectrum of cancer patients," commented Dr. Alessandro Riva, MD, Chairman and CEO of Transgene.

Key events and upcoming milestones

Individualized neoantigen therapeutic cancer vaccine (TG4050)

Significant progress has been made with Transgene’s myvac individualized cancer vaccine program in 2024:

ü Proof of principle data from Phase I part of the Phase I/II trial of TG4050 in the adjuvant setting of head and neck cancer. All TG4050-treated patients remained disease-free after median follow-up of 24.1 months (compared to three relapses in the control arm);
ü Phase II part of study launched in June 2024 based on these promising early data.

Positive data from Phase I part:

Transgene and NEC presented promising data from the ongoing randomized Phase I part of the Phase I/II trial (NCT04183166) of the neoantigen individualized therapeutic cancer vaccine, TG4050, at AACR (Free AACR Whitepaper) 2024 and at SITC (Free SITC Whitepaper) 2024 (see poster here).

In the Phase I part of the trial, all patients who received TG4050 after successful completion of adjuvant standard of care, remained disease-free and had not relapsed after a median follow-up of 24.1 months, comparing favorably to the observational arm which showed three out of 16 patients had relapsed (data cut-off: end of September 2024).

Transgene and Institut Curie also presented compelling immunogenicity data in patients, showing the induction of specific immune responses against selected personalized antigen targets. Additionally, immune responses were shown to be sustained over a 7-month period.

In this trial, primary objectives were safety and tolerability. Feasibility and disease-free survival (DFS) were secondary objectives. Exploratory objectives included immunogenicity and assessment of tumor biomarkers (TMB, PD-L1).

These data provide robust clinical proof of principle for Transgene’s lead asset in the adjuvant head and neck cancer setting, a patient population at risk of relapse.

Progress into Phase II part:

Based on the promising Phase I data, the randomized trial has progressed, with the Phase II part having started patient enrollment in June 2024, in collaboration with NEC.

Patient enrollment is progressing at a good pace and completion of randomization is expected in Q4 2025. In this trial, the primary objective is 24-month DFS (disease-free survival).

Upcoming news flow for TG4050 and the myvac platform:

Transgene’s objective for TG4050 is to extend DFS and reduce the risk of relapse. The Company will present 24-month DFS for all patients in the Phase I part of the Phase I/II trial in Q2 2025. In locally advanced, resectable head and neck cancers, 25% of patients are expected to relapse within 24 months after successful completion of surgery and adjuvant chemoradiotherapy (Cooper JS et al. NEJM, 2004; DY Lee et al. Head Neck, 2020).

These updated clinical data combined with innovation in the adjuvant treatment of operable head and neck cancer will be instrumental in determining TG4050’s optimal development path towards registration in this indication.

The myvac individualized cancer vaccine platform is applicable across a range of solid tumors where a significant unmet medical need remains, despite current and future treatment options, including immunotherapies.

Consequently, Transgene is starting initial preparations for a new Phase I trial in a second undisclosed indication, with the aim to initiate the trial in Q4 2025.

Other viral vector-based assets

Shared antigens cancer vaccine (TG4001)

In October 2024, Transgene announced that its randomized Phase II study evaluating TG4001 in combination with avelumab versus avelumab alone in patients with recurrent or metastatic HPV16-positive cervical and anogenital tumors did not meet its primary objective (improvement in progression-free survival).

However, analysis of a pre-planned subgroup of patients showed a positive efficacy trend in favor of the TG4001 containing regimen in cervical cancer patients.

Transgene is currently evaluating the full clinical and translational study results to determine the best way forward for this program. Clinical data from this trial will be presented at a scientific congress in Q2 2025.

BT-001 (oncolytic virus — intratumoral administration)

The Phase I/IIa trial (NCT04725331) is ongoing and the last patient in the Phase I part was enrolled in August 2024. In Part A of the trial, patients are given BT-001 as monotherapy, while in Part B, patients are given BT-001 in combination with pembrolizumab. In this part, KEYTRUDA (pembrolizumab) is provided by MSD (Merck & Co). KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Preliminary data were presented at ESMO (Free ESMO Whitepaper) 2024 (see press release here). The data indicated that BT-001 replicated in the tumor without being detectable in blood. As monotherapy and in combination with pembrolizumab, BT-001 was shown to be well tolerated. BT-001 also showed first signs of efficacy with clinical response in two out of six refractory patients, when given in combination with pembrolizumab, with shrinkage of injected and non-injected lesions. Treatment with BT-001 converted "cold" tumors into "hot" ones, and induced T-cell infiltration, as well as PD(L)-1 expression in the tumor microenvironment. Transgene and partner BioInvent are currently analyzing the second cohort of Part B of the Phase I to define the strategy for further development. Updated data is expected to be presented in H2 2025.

TG6050 (oncolytic virus — intravenous administration)

The Phase I Delivir trial, evaluating TG6050 in patients with advanced non-small cell lung cancer who have failed standard therapeutic options, has completed enrollment.

Initial data from the Phase I trial are expected to be reported in Q2 2025. Transgene will complete the analysis of these data to determine the best way forward for this candidate.

In July 2024, Transgene published preclinical data in the Journal for ImmunoTherapy of Cancer (JITC) (see article here), where the paper on TG6050 won the JITC Best Oncolytic and Local Immunotherapy Paper Award. The study demonstrated that TG6050 induces tumor regression in several "hot" and "cold" mouse tumor models. This antitumor activity was amplified when TG6050 was combined with an immune checkpoint inhibitor.

Transgene’s new leadership structure focused on accelerating the development of its innovative immunotherapy portfolio

To drive its ambitious strategic plan centered on the individualized cancer vaccine platform myvac, Transgene has gathered an expert leadership team.

Transgene’s Management Committee comprises the following members:

– Alessandro Riva, Chairman & Chief Executive Officer (CEO);

– Christophe Ancel, Chief Quality Officer & Qualified Pharmacist;

– Maurizio Ceppi, Chief Scientific Officer (CSO) (as of September 2024);

– Emmanuelle Dochy, Chief Medical Officer (CMO) (as of September 2024);

– John Felitti, General Counsel & Corporate Secretary;

– Lucie Larguier, Chief Financial Officer (CFO) (as of March 2024);

– Christelle Schwoerer, Chief Human Resources Officer (as of April 2024);

– Simone Steiner, Chief Technical Officer (CTO) (as of April 2025);

– James Wentworth, Chief Business Officer (CBO) (as of January 2024).

Key elements of the 2024 income statement

Operating revenue was €6.4 million in 2024 compared to €7.9 million in 2023. Operating revenue was mostly comprised of the Research Tax Credit (€6.0 million in 2024 and €6.4 million in 2023). The reduction in total operating revenue reflects the discontinuation of the AstraZeneca collaboration in 2023.
Net operating expenses stood at €42.0 million in 2024, compared to €37.9 million in 2023, reflecting intense activity on all clinical-stage candidates, including the preparation and launch of the Phase II part of the trial evaluating TG4050 in head and neck cancer. This activity is reflected in R&D expenses, at €34.3 million in 2024 versus €29.6 million in 2023. General and administrative expenses amounted to €7.8 million in 2024 (€7.0 million in 2023).
In 2024, the operating loss was €35.7 million, compared to a loss of €30.0 million in 2023.
Net loss was €34.0 million in 2024, compared to a net loss of €22.3 million in 2023.
The net cash burn was €27.7 million in 2024, compared to €24.0 million in 2023.
Cash available at year-end 2024 stood at €16.7 million, compared to €15.7 million at the end of 2023.

Business funded until the end of April 2026

The Company has signed a new amendment to the current account advance agreement with TSGH (Institut Mérieux), which increases the total amount of the facility by €15 million to €48 million. The Company has drawn down €22.5 million from this facility as of today.

With this credit facility and the support of TSGH (Institut Mérieux), the Company is now able to fund its business until the end of April 2026.

In July 2024, TSGH subscribed to Transgene a €33 million capital increase and requested the reimbursement of an equivalent amount from the current account advance. This reimbursement was carried out by way of set-off against the payment of the subscription price of the capital increase by TSGH.

The financial statements for 2024 as well as management’s discussion and analysis are attached to this press release (appendices A and B).

The Board of Directors of Transgene met on March 27, 2025, under the chairmanship of Dr. Alessandro Riva and closed the 2024 financial statements. Audit procedures have been performed by the statutory auditors and the auditor’s reports are in the process of being issued.

The Company’s universal registration document (URD), which includes the annual financial report, will be available early April 2025 on Transgene’s website, www.transgene.fr.

A conference call in English is scheduled today on March 27, 2025, at 6:00 p.m. CET (1:00 p.m. ET).

Webcast link to English language conference call:

View Source

On March 27, 2025 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, reported a business update and announced financial results for the quarter and full year ended December 31, 2024 (Press release, Immatics, MAR 27, 2025, View Source [SID1234651523]).

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"2025 will be marked by milestones across our TCR-T and TCR Bispecifics clinical portfolio, including advancing two of our main objectives for this year: firstly, reporting data on solid cancer types beyond melanoma, such as ovarian cancer, head and neck cancer and others and secondly, demonstrating that our next-generation, half-life extended TCR Bispecifics can deliver meaningful response rates in advanced solid cancer patients," said Harpreet Singh, Ph.D., CEO and Co-Founder of Immatics. "Additionally, the initiation of SUPRAME, the Phase 3 trial for our lead TCR-T cell therapy, IMA203, represents a transformative step in Immatics’ journey towards becoming a commercial-stage enterprise. We believe IMA203 offers patients and their treating physicians a cell therapy with impressive response rates and favorable tolerability in advanced melanoma. Notably, it requires no surgery or biopsy, has a fast turnaround time and a high manufacturing success rate. We are committed to rapidly delivering the first TCR therapeutic targeting PRAME to the market and to cancer patients, serving their unmet medical needs."

Full Year 2024 and Subsequent Company Progress

ACTengine Cell Therapy Programs

ACTengine IMA203 (PRAME)
IMA203 is Immatics’ lead TCR-T cell therapy, currently being evaluated in a Phase 3 trial (SUPRAME) in patients with previously treated advanced melanoma. IMA203 has the potential to become the first TCR therapeutic targeting PRAME to enter the market. In parallel, Immatics is priming its in-house, state-of-the-art TCR-T manufacturing facility to serve its planned commercial supply. In addition to maximizing the PRAME cell therapy opportunity, Immatics plans to expand IMA203 into uveal melanoma through the ongoing Phase 1b clinical trial. The current addressable patient population of PRAME/HLA-A*02:01-positive 2L unresectable or metastatic cutaneous melanoma in the US and EU52 is ~7,300 plus ~1,300 uveal melanoma patients in the US and EU5.

Clinical and commercial development plan for ACTengine IMA203 TCR-T
Based on the positive Phase 1b clinical data presented in 2024 and supported by the FDA RMAT designation3, Immatics has advanced its lead TCR-T product candidate, IMA203 targeting PRAME, into a randomized-controlled Phase 3 trial, called "SUPRAME" (NCT06743126). The trial commenced in December 2024. The first patient was randomized in the United States and enrollment continues as planned.

SUPRAME is a prospective, multicenter, open-label, randomized-controlled Phase 3 clinical trial evaluating the efficacy, safety and tolerability of IMA203 TCR-T in patients with unresectable or metastatic cutaneous melanoma who have received prior treatment with a checkpoint inhibitor. 360 HLA-A*02:01-positive patients will be randomized 1:1 to treatment with IMA203 or investigator’s choice of selected approved treatments in the 2L setting (nivolumab/relatlimab, nivolumab, ipilimumab, pembrolizumab, lifileucel (US), chemotherapy). Based on the Company’s discussions with the FDA, the primary endpoint for seeking full approval will be blinded independent central review ("BICR")-assessed (RECIST v1.1) progression-free survival (PFS). Given the expected median PFS of 2-3 months in this patient population4, as well as the median PFS of 6 months (> 1 year in patients with deep responses) observed in the data from the IMA203 Phase 1b trial, the Company has determined that utilizing PFS as the primary endpoint is the fastest pathway to seeking full approval and presents a more attractive commercial positioning as compared to objective response rate (ORR). Secondary endpoints for the trial include ORR, safety, DOR, OS and patient-reported outcomes.

The trial is planned to run internationally with approximately 50 sites in the United States and Europe.

Patient enrollment for SUPRAME is forecasted to be completed in 2026. A pre-specified interim data analysis will be triggered upon the occurrence of a defined number of events for PFS (progressive disease or death)5 anticipated to occur after approximately 200 patients are enrolled in 1Q 2026. The final analysis is planned for 4Q 2026. Immatics aims to submit a Biologics License Application (BLA) in 1Q 2027 for full approval and to launch IMA203 in 3Q 2027.

In addition to cutaneous melanoma, Immatics intends to expand the IMA203 TCR-T opportunity to treat uveal melanoma patients and will continue to evaluate IMA203 in this patient population through the ongoing Phase 1b trial.

Manufacturing capabilities
Immatics’ proprietary manufacturing process, timeline, capabilities and facility support late-stage clinical and commercial cell therapy development and supply.

IMA203 products are manufactured from a patient’s leukapheresis (with no surgery required) within 7 days, followed by 7-day QC release testing at >95% success rate6 to achieve the target dose (1-10×109 TCR-T cells). The Company’s state-of-the-art ~100,000 sq. ft. R&D and GMP manufacturing facility in the Houston Metropolitan Area was built with a modular design for efficient and cost-effective scalability (total of 8 manufacturing suites, plus further expansion space) to serve early-stage and registration-directed clinical trials as well as planned commercial supply. Through in-house manufacturing and QC testing, Immatics aims to better control the manufacturing process, shorten the turnaround time, ensure the manufacturing success rate and quality of the product and realize potential cost efficiencies, including manufacturing capacity optimization through scalability for a competitive and profitable commercial cell therapy product.

Clinical data on ACTengine IMA203 TCR-T as of October 2024
On October 10, 2024, Immatics provided a data update on IMA203 monotherapy in 28 heavily pretreated metastatic melanoma patients from the ongoing Phase 1b dose expansion part of the clinical trial in which patients were treated at the recommended Phase 2 dose (RP2D, 1 to 10 billion total TCR-T cells).

As of the data cut-off on August 23, 2024, treatment with IMA203 monotherapy in this melanoma patient population has demonstrated:

Confirmed objective response rate of 54% and an objective response rate of 62%
Disease control rate of 92% and tumor shrinkage in 88% of patients
12.1 months median duration of response, 6 months median progression-free survival and >1-year median progression-free survival in patients with deep responses
Median overall survival has not yet been reached at a median follow-up time of 8.6 months
IMA203 monotherapy has maintained a favorable tolerability profile with no treatment-related Grade 5 events in the entire safety population (N=70 Phase 1a and Phase 1b patients across all dose levels and all tumor types).

Immatics plans to present updated clinical data from the Phase 1b trial, including patients reported previously with longer follow-up and additional uveal melanoma patients, in 2025.

ACTengine IMA203CD8 TCR-T (GEN2) Monotherapy (PRAME)
IMA203CD8 is the Company’s second-generation cell therapy product candidate targeting PRAME. Given its pharmacology profile, once the target dose is reached, the Company intends to pursue the clinical development of this product in PRAME-positive solid cancers beyond melanoma, starting with gynecologic cancers.

On November 8, 2024, Immatics announced updated Phase 1 dose escalation clinical data on its next-generation ACTengine IMA203CD8 TCR-T cell therapy in 44 heavily pretreated HLA-A*02:01 and PRAME-positive patients with solid tumors, thereof 41 patients being evaluable for efficacy. Of note, these patients had been treated at substantially lower doses than IMA203 (GEN1), i.e. in a range of 0.2-0.48×109 TCR-T cells/m2 BSA (dose level 3) to 0.801-1.2×109 TCR-T cells/m2 BSA (dose level 4c) T cells infused.

As of the data cut-off on September 30, 2024, treatment with IMA203CD8 monotherapy demonstrated:

Confirmed objective responses observed in 41% of patients (at low doses, dose escalation ongoing)
Median duration of response of 9.2 months at a median follow-up of 13.1 months
Tumor shrinkage of target lesions in 84% of patients and disease control rate at week 6 of 85%
10 out of 17 responses were ongoing, of which three confirmed responses were ongoing at 14+, 15+ and 24+ months
Deep responses with ≥50% tumor size reduction were observed in 11 out of 17 responders. This group included two patients with complete response of target lesions, of which one patient showed a complete metabolic response according to a PET-CT scan

IMA203CD8 monotherapy has maintained a manageable tolerability profile in the 44 patients treated.

Based on the enhanced pharmacology of IMA203CD8 demonstrated in this trial, the evaluation of higher doses of IMA203CD8 in the ongoing dose escalation trial opens the possibility of addressing hard-to-treat solid tumor indications with both high- and medium-level PRAME copy numbers, such as ovarian cancer, uterine cancer, squamous non-small cell lung carcinoma, triple negative breast cancer and others.

The next clinical data update including dose escalation and ovarian cancer is planned in 2025.

TCR Bispecifics Programs

TCER IMA402 (PRAME)

To expand the PRAME opportunity to additional solid cancer types and earlier lines of treatment, the Company is focusing on its half-life extended TCR Bispecific, IMA402. Upon delivering clinical proof-of-concept ("PoC") in last-line melanoma, Immatics plans to explore its potential in gynecologic cancers, sqNSCLC, breast cancer and other solid tumor indications as well as earlier lines of solid cancers, such as first-line (1L) cutaneous melanoma.

On November 18, 2024, Immatics announced the first clinical data update from the ongoing Phase 1 dose escalation trial evaluating its next-generation, half-life extended TCR Bispecific molecule, TCER IMA402 targeting PRAME, in 33 heavily pretreated (3 median lines of prior therapies) HLA-A*02:01-positive patients with recurrent and/or refractory solid tumors.

As of the data cut-off on November 6, 2024, treatment with IMA402 demonstrated a favorable tolerability profile in the 33 patients treated.

Early pharmacokinetic data indicated a median half-life of approximately seven days, potentially enabling bi-weekly dosing. Initial signs of clinical anti-tumor activity have been observed and are associated with PRAME expression and IMA402 dose levels administered (up to 4 mg at DL8).

In the PRAME-negative patient population across all doses and indications, only one patient out of seven (14%) showed tumor shrinkage of -2.9%
25% (3/12) of patients (PRAME+ or not tested) treated at low doses (DL1-6) showed tumor shrinkage, including one unconfirmed partial response in cutaneous melanoma
78% (7/9) of patients (PRAME+ or not tested) treated at relevant doses (8 patients at DL7 and 1 patient at DL8) experienced shrinkage of their target lesions, including one confirmed partial response in melanoma ongoing at 3 months and three patients with ongoing stable disease at 6+ weeks (cut. melanoma), 3 months (ovarian cancer), 8+ months (uveal melanoma)

Based on the initial signs of dose-dependent and PRAME target expression-dependent clinical activity observed during dose escalation, the Company will continue to evaluate IMA402 at higher dose levels to determine the optimal therapeutic dose.

As of March 27, 2025, dose escalation remains ongoing at DL10 (8 mg) with MTD not reached.

The next update on the Phase 1a trial with clinical data at relevant dose levels in second-line and later melanoma is planned in 2025.

TCER IMA401 (MAGEA4/8)
Immatics is further harnessing the potential of its proprietary bispecific platform to develop innovative therapeutics and unlock more cancer types. The Company’s half-life extended TCR Bispecific, IMA401 targeting MAGEA4/8, is progressing through a Phase 1 trial in patients with sqNSCLC, HNSCC, bladder cancer and other solid tumor indications, with the primary goal of developing this product candidate in earlier treatment lines.

On September 16, 2024, Immatics announced 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) (Free ESMO Whitepaper) Congress 2024.

As of data cut-off on July 23, 2024, 35 heavily pretreated patients with recurrent and/or refractory solid tumors were treated with IMA401 monotherapy across nine escalating dose levels. The treated patient population was composed of patients with 16 different solid tumor indications who were 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 had an ECOG performance status of ≥ 1.

Proof-of-concept clinical data from the Phase 1a first-in-human dose escalation basket trial showed initial anti-tumor activity in multiple tumor types, durable objective responses, including confirmed responses ongoing at 13+ months, a manageable tolerability profile and a half-life of 14+ days.

Treatment with IMA401 monotherapy in patients with relevant IMA401 doses and MAGEA4/8high levels (N=17) demonstrated:

Objective response rate of 29% with confirmed responses observed in 25% of patients
Disease control rate of 53% and tumor shrinkage of 53%
As the clinical trial progresses, the Company aims to further leverage the potential of IMA401 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. By further combining IMA401 with a checkpoint inhibitor, Immatics aims to generate relevant clinical data to position IMA401 as a combination therapy in earlier treatment lines.

The next update on IMA401 Phase 1a data, with a focus on head and neck cancer, is expected in 2025, and the Company plans to share data with a focus on non-small cell lung carcinoma in 2026.

Corporate Development

IMA203 and mRNA Combination (Moderna collaboration): In February 2025, the FDA granted IND clearance for a Phase 1 trial evaluating Immatics’ IMA203 PRAME TCR-T in combination with Moderna’s PRAME adaptive immune modulating therapy. The objective of the combination is to further enhance IMA203 T cell responses with the potential to significantly reduce turn-around time and costs through the infusion of a much lower cell dose. The first-in-human, Phase 1a/1b trial is a multicenter, open-label, dose escalation/de-escalation (adaptive design) trial evaluating the safety, tolerability and efficacy of the combination therapy in up to 15 patients with advanced or recurrent cutaneous melanoma and synovial sarcoma. Immatics is responsible for conducting the Phase 1 trial. Each party retains full ownership of its investigational PRAME compound, and the parties will fund the clinical study on a cost sharing basis. In November 2024, Immatics presented preclinical proof-of-concept data at SITC (Free SITC Whitepaper) supporting this combination.
In September 2024, Immatics regained full clinical development and commercialization rights to IMA401 due to ongoing portfolio prioritization efforts within Bristol Myers Squibb. The Phase 1 trial with IMA401 is ongoing and will continue to be conducted by Immatics.
Full Year 2024 Financial Results

Cash Position: Cash and cash equivalents as well as other financial assets total $628.0 million1 (€604.5 million) as of December 31, 2024, compared to $442.5 million1 (€425.9 million) as of December 31, 2023. The increase is mainly due to the public offering in January and October 2024, partly offset by ongoing research and development activities.

Revenue: Total revenue, consisting of revenue from collaboration agreements, was $161.9 million1 (€155.8 million) for the year ended December 31, 2024, compared to $56.1 million1 (€54.0 million) for the year ended December 31, 2023. The increase is mainly the result of the one-time revenue associated with the termination of the IMA401 and ACTallo collaborations by Bristol Myers Squibb during the year ended December 31, 2024.

Research and Development Expenses: R&D expenses were $153.9 million1 (€148.1 million) for the year ended December 31, 2024, compared to $123.3 million1 (€118.7 million) for the year ended December 31, 2023. The increase mainly resulted from costs associated with the advancement of the product candidates in clinical trials.
General and Administrative Expenses: G&A expenses were $48.2 million1 (€46.4 million) for the year ended December 31, 2024, compared to $39.7 million1 (€38.2 million) for the year ended December 31, 2023.

Net Profit and Loss: Net profit was $15.8 million1 (€15.2 million) for the year ended December 31, 2024, compared to a net loss of $98.3 million1 (€94.6 million) for the year ended December 31, 2023. The net profit largely resulted from the one-time revenue from collaborations, offset by ongoing expenses.

Full financial statements can be found in our Annual Report on Form 20-F filed with the Securities and Exchange Commission (SEC) on March 27, 2025, and published on the SEC website under www.sec.gov.

Upcoming Investor Conferences

Bank of America Healthcare Conference, Las Vegas (NV) – May 13 – 15, 2025
Jefferies Global Healthcare Conference, New York (NY) – June 3 – 5, 2025
To see the full list of events and presentations, visit View Source