Major R&D milestones achieved in 2019 and strong clinical activity in 2020

­         Multiple milestones achieved in 2019, allowing the first myvac® and Invir.IO™ based candidates to enter the clinic

 

­         Clinical results expected in the coming months for TG4001 and TG6002

 

­         Successful collaborations with AstraZeneca and NEC highlighting the quality of the new platforms, Invir.IO™ and myvac® respectively

Strasbourg, France, March 11, 2020, 5:45 p.m. CET – Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of cancer, publishes its financial results for 2019 and provides an update on its product portfolio.

 

Philippe Archinard, Chairman and Chief Executive Officer of Transgene, commented: 

 

“We achieved multiple important advances with our novel myvac® and Invir.IO™ platforms during the course of 2019. We completed all the regulatory steps required to start the US and European clinical trials of TG4050, the first individualized therapeutic vaccine based on the myvac® platform in January 2020. The clinical development is being co-funded by our partner NEC. 

Our collaboration with AstraZeneca, based on our Invir.IO™ platform, is progressing well with the first multifunctional oncolytic viruses already being delivered to them. This platform has also generated a number of exciting new oncolytic candidates, including BT-001, which is being co-developed with BioInvent. The preclinical results generated with BT-001 have been remarkable and we are working hard to make sure we can take our first multifunctional Invir.IO™ oncolytic into the clinic before the end of 2020.

On the clinical front, we had a year of contrasts with on the one hand, the very encouraging initial results of TG4001, which were presented at ESMO 2019, and on the other hand, the disappointing outcome of the Phase 2 trial of TG4010 and the decision to stop Pexa-Vec trials in HCC.

We remain confident in the potential of our four clinical assets TG4001, TG4050, TG6002 and BT-001 as well as in our highly innovative technologies and platforms myvac® and Invir.IO™.

We also have sufficient financial visibility to pursue our developments with determination and confidence.”

2020: multiple clinical milestones expected

 

Transgene's portfolio currently consists of four immunotherapy drug candidates in clinical development:

­          Two therapeutic vaccines: TG4001 currently being evaluated in a Phase 2 trial and TG4050, the first individualized treatment based on the myvac® platform, assessed in two Phase 1 trials.

­          Two oncolytic viruses: TG6002, which is being assessed in two Phase 1/2a trials, and BT-001, the first oncolytic virus based on the Invir.IO™ platform, and which is expected to enter the clinic before the end of 2020.

 

Clinical results for TG4001 and TG6002 are expected in the second quarter of 2020:

­          The Phase 2 trial of TG4001 in combination with avelumab in HPV-positive cancers is ongoing. Patient recruitment is in line with projections and interim results are expected in the second quarter of 2020.

­          The Phase 1 trial of TG6002 administered intravenously in patients with gastrointestinal cancers is ongoing. First data are also expected in the second quarter of 2020.

 

With myvac® and Invir.IO™, Transgene has two next-generation platforms whose potential has been validated by collaboration deals with NEC and AstraZeneca respectively:

 

myvac® platform

­          Transgene is developing the therapeutic vaccine TG4050, together with NEC. This is the first individualized vaccine based on the myvac® platform. It integrates NEC’s Artificial Intelligence technologies. These technologies are used to select the most relevant mutations (neoantigens) that are integrated into the TG4050 vaccine. These AI technologies will also contribute to the in-depth analysis of the patient’s immune characteristics, in order to determine the profiles of those who responded to the vaccine.

­          Data validating the vaccine design principle behind TG4050 are being actively promoted and will be presented at several specialized international congresses.

­          The first clinical trials assessing TG4050 are ongoing in Europe and in the United States. They are including patients with ovarian cancers and head and neck cancers. NEC is financing 50% of their cost.

­          The clinical trials are a central part of a broad program of translational research in collaboration with expert centers both in the US and Europe. This program will generate a significant body of data evaluating the activity of TG4050 from these initial clinical trials. The first data are expected in 1H 2021.

­          The Company has set up an in-house good manufacturing practice (GMP) unit dedicated to the manufacturing of the individualized batches of TG4050 needed for the current Phase 1 trials.

­          The myvac® project is supported by Bpifrance, within the NEOVIVA program. The NEOVIVA project aims to strengthen the development of this highly innovative technology together with three partners: HalioDx, Traaser and Institut Curie. €2.6 million have been allocated to Transgene over five years. The NEOVIVA project is complimentary to the collaboration between Transgene and NEC.

 

Invir.IO™ platform

­          BT-001 is the first oncolytic virus from the Invir.IO™ platform. It is based on Transgene’s patented viral vector VV_copTK^-RR^- which has been designed to encode BioInvent’s anti-CTLA4 antibody (an immune checkpoint inhibitor) as well as the cytokine GM-CSF.

­          Preclinical results with BT-001 have been extremely promising, with treatment leading to the eradication of tumors in several murine models known for their low sensitivity to immune checkpoint inhibitors. These data will be presented at scientific congresses in the coming months. A first-in-human trial is being prepared and BT-001 is expected to enter the clinic before the end of 2020.

­          The collaboration with AstraZeneca is highly productive with Transgene already delivering the first multi-armed oncolytic viruses to its partner. As a result, Transgene has received $10 million at the time the collaboration was signed and booked €1.3 million related to the achievement of certain preclinical milestones. In 2020, Transgene will continue to design further oncolytic viruses for this collaboration. AstraZeneca can exercise an option to further develop each of these novel drug candidates.

­          Transgene’s patented viral vector, which underpins the Invir.IO™ platform, allows the development of a wide range of multifunctional oncolytic viruses. Transgene has already designed a number of proprietary oncolytic viruses that are being evaluated in preclinical models. A candidate is expected to be selected with the aim of submitting a clinical trial application in 2H 2020 ahead of starting a clinical trial in 2021.

 

Summary of key ongoing clinical trials

 

TG4001 + Bavencio® (avelumab) Phase 2

Targets: HPV16 E6 and E7 oncoproteins HPV-positive cancers including oropharyngeal head and neck cancer – 2nd line ü Clinical collaboration with Merck KGaA and Pfizer, for the supply of avelumab ü Publication of the results of a Phase 2b trial of TG4001 in Gynecologic Oncology  (April 2019), demonstrating the biological activity of this immunotherapeutic in CIN 2/3 lesions; editorial in The Lancet Oncology (April 2019) ü Positive results of the Phase 1b part of the trial presented at ESMO (Sept. 2019) Three of the six patients who received the recommended dose responded to the treatment. The observed responses were durable. Ü Interim Phase 2 results expected in 2Q 2020

 

myvac® TG4050 Phase 1	Targets: tumor neoantigens Ovarian cancer – after first-line surgery and adjuvant therapy ü Trial authorized in the United States (May 2019) and in France (Sept. 2019) ü Principal investigator: Matthew Block (Mayo Clinic) ü First patient enrolled in January 2020 Ü First data expected in 1H 2021
myvac® TG4050 Phase 1	HPV-negative head and neck cancer – after surgery and adjuvant therapy ü Trial authorized in the United Kingdom (July 2019) and in France (Sept. 2019) ü Principal investigator: Christian Ottensmeier (Southampton University) ü First patient enrolled in January 2020 Ü First data expected in 1H 2021

 

TG6002 Phase 1/2a

Payload: FCU1 for the local production of a chemotherapy agent Gastro-intestinal adenocarcinoma (colorectal cancer for Phase 2) – Intravenous (IV) route ü Publication in Molecular Therapy Oncolytics (March 2019) highlighting the promising activity of TG6002 in preclinical colorectal carcinoma models ü Multicenter trial ongoing in Belgium, France and Spain ü Last dose levels currently being evaluated (Phase 1 part) Ü First results of the Phase 1 part expected in 2Q 2020

TG6002 Phase 1/2a

Colorectal cancer with liver metastasis – Intrahepatic artery (IHA) route ü Multicenter trial authorized in the United Kingdom (July 2019) ü First patient treated in February 2020 Ü First results expected in 1H 2021 (Phase 1 part)

 

Invir.IO™ BT-001 Phase 1/2

Payload: anti-CTLA4 antibody and GM-CSF cytokine Solid tumors ü Collaboration with BioInvent ü First clinical trial application submitted Ü Presentation of very encouraging preclinical results at upcoming scientific congresses Ü First clinical trial expected to start before the end of 2020

 

Key financials for 2019

 

-          Operating income of €13.7 million in 2019, compared to € 42.9 million in 2018.

R&D services for third parties amounted to €6.7 million in 2019 (€1.3 million in 2018). This significant increase is mainly due to the collaboration signed with AstraZeneca in 2019. This generated €5.3 million in revenue in 2019. The research tax credit amounted to €6.5 million in 2019 (€5.7 million euros in 2018). As a reminder, the much higher operating income figure in 2018 was mainly the result of the €35.6 million income generated by the transaction with Tasly Biopharmaceuticals Co, Ltd.

• Net operating expenses of €39.2 million in 2019, compared to €35.5 million in 2018.

R&D expenses increased to €31.4 million in 2019 (from €27.3 million in 2018), due to the acceleration of external expenses for clinical projects and the setup of manufacturing unit dedicated to small clinical batches. General and administrative expenses stood at €7.1 million in 2019 versus €7.0 million in 2018.

• Financial income of €6.7 million in 2019 versus a loss of €2.0 million in 2018.

The decision taken at the end of 2019 to stop the clinical development of TG4010 has led to a downward reassessment of the financial debt related to the repayable advances of the ADNA program of €8.7 million. This has been recognized as financial income.

-          Net loss of €18.8 million in 2019, compared to a net profit of €8.0 million in 2018.

-          Cash burn reduced to €20.5 million in 2019 (excluding the proceeds of the rights issue), versus €24.5 million in 2018.

Transgene received €8.9 million in June 2019, following the signing of the contract with AstraZeneca. This contributed to the reduced net cash burn compared to 2018 despite an increase in operating expenses during the period.

-          Cash available at year-end 2019: €43.3 million, compared to €16.9 million at the end of 2018, due to the successful €48.7 million rights issue completed in July 2019.

-          Transgene expects its cash burn for 2020 to be around €25 million.

 

The financial statements for 2019 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 11, 2020, under the chairmanship of Philippe Archinard and closed the 2019 financial statements. Audit procedures have been performed by the statutory auditors and the delivery of the auditors’ report is ongoing.

 

The Company’s universal registration document, which includes the annual financial report, will be available early April 2020 on Transgene’s website, www.transgene.fr.