Transgene Achieves Key Milestones in 2024, Including Clinical Proof of Principle for Individualized Cancer Vaccine ̶ Strong Outlook for 2025

• Clinical proof of principle obtained in Phase I adjuvant head and neck cancer trial with individualized cancer vaccine TG4050  ̶  Further data on 24-month follow-up for all patients of the Phase I part expected in Q2 2025

• Randomization in Phase II part of the Phase I/II trial evaluating TG4050 in head and neck cancer patients due to be completed in Q4 2025

• New trial with individualized cancer vaccine planned to start in Q4 2025 in a second indication

• Business funded until the end of April 2026

Conference call scheduled today at 6 p.m. CET (in English). See details below.

Strasbourg, France, March 27, 2025, 5:45 p.m. CET – Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of cancer, today publishes its financial results for 2024, and provides an update on its product pipeline and outlook for 2025.

“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 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.

Individualized neoantigen therapeutic cancer vaccine (TG4050)

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

• 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);
• 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 2024 and at SITC 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.

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 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:

https://edge.media-server.com/mmc/p/w9y84tms

Please log in to the following link to obtain your personal telephone IDs: https://register.vevent.com/register/BI913c7946a95044e58cbf4b40ff8155b9

A replay of the call will be available on the Transgene website (www.transgene.fr) following the live event.