Transgene SA

Top line data show that the randomized Phase II study of TG4001 in combination with avelumab versus avelumab alone in patients with recurrent or metastatic HPV16-positive cervical and anogenital tumors did not meet the primary objective of improvement in progression-free survival Pre-planned subgroup analysis showed a positive efficacy trend in favor of the TG4001 containing regimen in patients with cervical cancer Transgene will complete full analysis of the data before deciding on the best way forward for TG4001 STRASBOURG, France I October 14, 2024 I Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of cancer, announces that its randomized Phase II study to evaluate TG4001 in combination with avelumab versus avelumab alone in patients with recurrent or metastatic HPV16-positive cervical and anogenital tumors has not met the primary objective of the study (improvement in progression-free survival). The pre-planned subgroup analysis showed a positive efficacy trend in favor of the TG4001 containing regimen in cervical cancer patients, which requires further confirmation through additional analyses, including by PD-L1 status. These patients account for approximately half of the patients enrolled in the study. The treatment has been well tolerated. Adverse events are consistent with previous observations. Transgene is currently evaluating the full study results in detail to determine the best way forward for this program and will communicate further once this is completed. Dr. Alessandro Riva, Chairman and CEO of Transgene , said: “Failure to meet the primary objective in our Phase II study with TG4001 is disappointing. Nevertheless, we are encouraged by the positive efficacy trend in favor of the combination regimen in cervical cancer patients. We plan to complete a full and rigorous analysis of the data before deciding on any path forward for this asset, in particular in cervical cancer, in the context of the evolving treatment landscape. The complete study results will be presented at an upcoming scientific conference.  We would like to thank all the patients and caregivers who have taken part in this study for their important contribution. With a diversified portfolio of novel immunotherapies targeting solid tumors, our strategy remains focused on advancing our lead asset, TG4050, an individualized cancer vaccine for head and neck cancers for use following surgery and adjuvant therapy. We expect to report additional data on TG4050 from the 24-month median follow-up of Phase I patients in our head and neck cancer trial in November 2024 at the SITC conference.” A conference call in English is scheduled today, October 14, 2024, at 3:30 p.m. CET (9:30 p.m. ET). Webcast link to English language conference call: https://edge.media-server.com/mmc/p/zh5cy2u9/ Please log in to the following link to obtain your personal telephone IDs. A replay of the call will be available on the Transgene website (www.transgene.fr) following the live event. About TG4001 TG4001 (tipapkinogen sovacivec) is an investigational therapeutic vaccine based on a non-propagative, highly attenuated Vaccinia vector (MVA), which is engineered to express HPV16 antigens (E6 & E7) and an adjuvant (IL-2). TG4001 is designed to have a two-prolonged antiviral approach: to alert the immune system specifically to cells presenting the HPV16 E6 and E7 antigens, that can be found in HPV16-related tumors, and to further stimulate the infection-clearing activity of the immune system through interleukin 2 (IL-2). TG4001 has been administered to more than 350 individuals. Its mechanism of action and good safety profile make TG4001 an excellent candidate for combinations with other therapies in HPV-mediated solid tumors. About the trial TG4001 was evaluated in a multi-center, open label, randomized Phase II trial (NCT03260023) designed to compare the efficacy of the combination of TG4001 and avelumab versus avelumab alone in patients with recurrent or metastatic HPV16-positive cervical and anogenital cancers who have disease progression after a maximum of one line of systemic treatment, or who are not eligible for first-line chemotherapy. The overall trial enrolled 100 patients. About Transgene Transgene (Euronext: TNG) is a biotechnology company focused on designing and developing targeted immunotherapies for the treatment of cancer. Transgene’s programs utilize viral vector technology with the goal of indirectly or directly killing cancer cells. The Company’s clinical-stage programs consist of a portfolio of therapeutic vaccines and oncolytic viruses: TG4050, the first individualized therapeutic vaccine based on the myvac® platform, TG4001 for the treatment of HPV-positive cancers, as well as BT-001 and TG6050, two oncolytic viruses based on the Invir. IO® viral backbone. With Transgene’s myvac ® platform, therapeutic vaccination enters the field of precision medicine with a novel immunotherapy that is fully tailored to each individual. The myvac ® approach allows the generation of a virus-based immunotherapy that encodes patient-specific mutations identified and selected by Artificial Intelligence capabilities provided by its partner NEC. With its proprietary platform Invir. IO®, Transgene is building on its viral vector engineering expertise to design a new generation of multifunctional oncolytic viruses. Additional information about Transgene is available at: www.transgene.fr Follow us on social media: X (formerly Twitter): @TransgeneSA – LinkedIn: @Transgene SOURCE: Transgene

Transgene’s Phase II trial of viral-based vaccine TG4001 failed to meet its primary endpoint. Credit: Kitsawet Saethao via Shutterstock. Transgene ’s stock has dropped after a Phase II trial of its therapeutic vaccine candidate TG4001 (tipapkinogene sovacivec) failed to meet its primary endpoint of improvement in progression-free survival (PFS) in solid tumours. Transgene’s share price fell 18.8% from €1.17 at close on 11 October to a low of €0.95 on Monday morning (14 October) after the announcement, settling at around €1 per share. The trial (NCT03260023) aimed to assess the impact of TG4001 in combination with Merck KgaA’s  Bavencio (avelumab), a PD-L1 checkpoint inhibitor, in 150 patients with recurrent or metastatic HPV16-positive cervical and anogenital cancers who were either treatment-naïve or had one prior systemic chemotherapy, but no earlier immunotherapy. The addition of TG4001 did not produce statistically significant improvements in PFS across the study population, however, Transgene said it remains optimistic. In a subgroup of patients with cervical cancer – comprising about 54% of the trial population – the data suggested a potential trend towards improved PFS. The French biotech is planning further analysis, including examining the data by PD-L1 status, before deciding on the next steps for the candidate’s development. PD-L1 status refers to the level of expression of the PD-L1 protein on tumour cells, which can influence how well a patient’s cancer responds to Bavencio. See Also: Bayer applies for EU approval of menopause drug elinzanetant ENHERTU gains conditional approval in China to treat NSCLC TG4001, a viral-based vaccine, works by inducing an immune response against cells expressing the HPV16 E6 and E7 antigens, aided by the inclusion of human IL-2 to strengthen this immune reaction. In the announcement accompanying the data, Transgene’s CEO Alessandro Riva said: “Failure to meet the primary objective in our Phase II study with TG4001 is disappointing. Nevertheless, we are encouraged by the positive efficacy trend in favour of the combination regimen in cervical cancer patients.” Transgene said that it remains focused on its lead asset TG4050 , an individualised cancer vaccine that is in a Phase I/II trial (NCT04183166) in patients with head and neck cancer. TG4050 is based on Transgene’s myvac platform, which generates personalised therapies, based on patient-specific mutations (neoantigens), that are designed to induce a T cell response to tumour cells. The company expects to share 24-month data on Phase I patients in November at the Society for Immunotherapy of Cancer (SITC) conference. According to a GlobalData report , cancer vaccines are a key immuno-oncology development trend. TG4050 is a personalised vaccine, whereas TG4001 is an off-the-shelf standardised treatment. According to over half of high-prescribing key opinion leaders who responded to a GlobalData survey in 2023, personalised mRNA vaccines are the most promising cancer vaccine type. GlobalData is the parent company of Clinical Trials Arena. The company is also developing an oncolytic virus therapy, BT-001, for treating solid tumours in partnership with BioInvent International . The therapy is being evaluated in a Phase I/IIa clinical trial (NCT04725331) as a single agent and in combination with MSD’s PD-1 checkpoint inhibitor Keytruda (pembrolizumab). Transgene’s journey with oncolytic virus therapies has been challenging. In May 2023, AstraZeneca ended its four-year partnership with the company, a collaboration formed in 2019 with a $10m upfront payment to Transgene to develop oncolytic virus candidates. The partnership’s troubles started early, as one of Transgene’s candidates Pexa-Vec failed a Phase III trial (NCT02562755) just months after the deal was signed.

LUND, Sweden, and STRASBOURG, France I September 14, 2024 I BioInvent International AB (“BioInvent”) (Nasdaq Stockholm: BINV), a biotech company focused on the discovery and development of novel and first-in-class immune-modulatory antibodies for cancer immunotherapy, and Transgene (Euronext Paris: TNG) , a biotech company that designs and develops virus-based immunotherapies for the treatment of cancer, today announce new initial data from their ongoing Phase 2/2a study on the multifunctional oncolytic virus BT-001, demonstrating antitumor activity in patients with refractory solid tumors . The data presented today at the2024European Society for Medical Oncology (ESMO) Annual Meeting, showed that BT-001 induced tumor regression in patients unresponsive to prior anti PD(L)-1 treatment, both as a monotherapy and in combination with MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy KEYTRUDA® (pembrolizumab). Preliminary translational data suggest that BT-001 replicates in the tumor where the payloads are expressed with undetectable systemic exposure . BT-001 alone or in combination with pembrolizumab was well tolerated and showed first signs of efficacy with clinical responses in 2 of 6 refractory patients when given in combination with pembrolizumab. BT-001 treatment turned “cold” tumors to “hot” inducing T cell infiltration , a higher M1/M2 ratio , and a shift toPD(L)-1 positivity in the tumor microenvironment . Dr. S. Champiat, Medical Oncologist, Head of the Inpatient Unit, Drug Development Department (DITEP) at Institut Gustave Roussy , commented:”The immunological data generated by BT-001 suggest that, as hoped, BT-001 is replicating in the tumor and its payload of transgenes is expressed, with very limited exposure outside of the tumor thereby limiting systemic toxicity. I look forward to additional results from this ongoing study which will provide further evidence of the safety and clinical activity of BT-001 and its potential role as a new therapy for cancer patients with solid tumors. “ Transgene and BioInvent are co-developing BT-001, an oncolytic virus developed using Transgene’s Invir.IO® platform armed to express GM-CSF and BioInvent’s full-length anti-CTLA-4 monoclonal antibody, to elicit a strong and effective anti-tumoral response in solid tumors. Alessandro Riva, Chairman and CEO of Transgene , said: “We are pleased to present the first promising clinical data on BT-001 at ESMO 2024 which confirm its mechanism of action as a single agent injected intratumorally and importantly demonstrate first signs of anti-tumor activity. Added to its good safety profile alone and in combination with pembrolizumab, BT-001 has the potential to shrink lesions and induce stable disease in refractory patients who may have few other treatment options. We will further explore the safety and efficacy of BT-001 in this development program with our partner BioInvent and report additional data when it becomes available.” Andres McAllister, MD, PhD, Chief Medical Officer at BioInvent International AB, concluded: “We are encouraged by the early clinical results presented at ESMO for BT-001, which encodes a potent Treg-depleting recombinant human anti-CTLA-4 antibody generated by our proprietary n-CoDeR® and F.I.R.S.T™ platforms,. This clinical proof of concept confirms our ability to identify antibodies that bind to a selected target but exhibit a differentiated activity, allowing the development of promising new drug candidates such as BT-001.” The abstract and Poster titled: “Initial clinical results of BT-001, an oncolytic virus expressing an anti-CTLA4 mAb, administered as single agent and in combination with pembrolizumab in patients with advanced solid tumors.” . The poster can be accessed at the company’s website https://www.bioinvent.com/en/our-science/scientific-publications . KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. About the trial The ongoing Phase 1/2a ( NCT: 04725331 ) study is a multicenter, open label, dose-escalation trial evaluating BT-001 as a single agent and in combination with pembrolizumab (anti-PD-1 treatment). Patient inclusions are ongoing in Europe (France, Belgium) and the trial has been authorized in the US. Phase 1 is divided into two parts. In part A, patients with metastatic/advanced tumors receive single agent, intra-tumoral administrations of BT-001. Part B explores the combination of intra-tumoral injections of BT-001 with pembrolizumab. In this part, KEYTRUDA® (pembrolizumab) is provided to the trial by MSD (Merck & Co). Phase 2a will evaluate the combination regimen in several patient cohorts with selected tumor types. These expansion cohorts will offer the possibility of exploring the activity of this approach to treat other malignancies not traditionally addressed with this type of treatment. About BT-001 BT-001 is an oncolytic virus generated using Transgene’s Invir.IO® platform and its patented large-capacity VVcopTK-RR- oncolytic virus, which has been engineered to encode both a Treg-depleting human recombinant anti-CTLA-4 antibody generated by BioInvent’s proprietary n-CoDeR®/F.I.R.S.T™ platforms, and the human GM-CSF cytokine. By selectively targeting the tumor microenvironment, BT-001 is expected to elicit a much stronger and more effective antitumoral response. As a consequence, by reducing systemic exposure, the safety and tolerability profile of the anti-CTLA-4 antibody may be greatly improved. BT-001 is being co-developed as part of a 50/50 collaboration on oncolytic viruses between Transgene and BioInvent. To know more on BT-001, watch our video here . About BioInvent BioInvent International AB (Nasdaq Stockholm: BINV) is a clinical-stage biotech company that discovers and develops novel and first-in-class immuno-modulatory antibodies for cancer therapy, with currently four drug candidates in five ongoing clinical programs in Phase 1/2 trials for the treatment of hematological cancer and solid tumors, respectively. The Company’s validated, proprietary F.I.R.S.T™ technology platform identifies both targets and the antibodies that bind to them, generating many promising new drug candidates to fuel the Company’s own clinical development pipeline and providing licensing and partnering opportunities. The Company generates revenues from research collaborations and license agreements with multiple top-tier pharmaceutical companies, as well as from producing antibodies for third parties in the Company’s fully integrated manufacturing unit. More information is available at www.bioinvent.com . Follow on Twitter: @BioInvent. More information is available at www.bioinvent.com . Follow us on Twitter: @BioInvent About Transgene Transgene (Euronext: TNG) is a biotechnology company focused on designing and developing targeted immunotherapies for the treatment of cancer. Transgene’s programs utilize viral vector technology with the goal of indirectly or directly killing cancer cells. The Company’s clinical-stage programs consist of a portfolio of therapeutic vaccines and oncolytic viruses: TG4050, the first individualized therapeutic vaccine based on the myvac ® platform, TG4001 for the treatment of HPV-positive cancers, as well as BT-001 and TG6050, two oncolytic viruses based on the Invir.IO® viral backbone. With Transgene’s myvac ® platform, therapeutic vaccination enters the field of precision medicine with a novel immunotherapy that is fully tailored to each individual. The myvac ® approach allows the generation of a virus-based immunotherapy that encodes patient-specific mutations identified and selected by Artificial Intelligence capabilities provided by its partner NEC. With its proprietary platform Invir.IO®, Transgene is building on its viral vector engineering expertise to design a new generation of multifunctional oncolytic viruses.Additional information about Transgene is available at: www.transgene.fr Follow us on social media: X (formerly Twitter): @TransgeneSA – LinkedIn: @Transgene SOURCE: BioInvent