Transgene and NEC Announce Positive Preliminary Data from Phase I Studies of TG4050, a Novel Individualized Neoantigen Cancer Vaccine

Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of cancer, and NEC Corporation (NEC; TSE: 6701), a leader in IT, network and AI technologies, today announce positive preliminary immunogenicity and clinical data on TG4050, their jointly developed individualized neoantigen cancer vaccine. TG4050 is the first candidate based on Transgene‘s myvac platform. Powered by NEC‘s cutting-edge AI capabilities, it is being evaluated in two ongoing multicenter Phase I trials in patients with ovarian cancer and head and neck cancer.

“We are extremely pleased to demonstrate the ability of TG4050 to effectively prime the immune system of the first patients who received this novel treatment and observe first signals of clinical activity. We believe this establishes the potential role of TG4050 as a new approach for individualized cancer vaccination. TG4050 appears to demonstrate a favorable safety profile thus far. We have also confirmed the feasibility of the “needle to needle” process with these two multicenter international Phase I trials, using our own internal manufacturing facility. Strikingly, when supported by NEC‘s powerful prediction tool, the myvac viral vector used in TG4050, which has been genetically optimized to improve immunogenicity and peptides presentation, induced robust and consistent response against class I and class II epitopes. We are working hard to complete the studies to further confirm these findings and generate additional immune and clinical data. We are very excited by the potential of TG4050 and hope to share additional data at a major oncology congress in 2022. Based on the additional data, we will identify the most appropriate path to take TG4050 forward,” commented Hedi Ben Brahim, Chairman and CEO of Transgene.

“We are very excited to see early signs of clinical activity in the TG4050 clinical trials that uses our AI-driven neoantigen prediction system. NEC‘s proprietary machine learning algorithms are built upon decades of AI expertise, enabling us to prioritize and map the most immunogenic neoantigens on personalized vaccine blueprints. The safety profile and early immunogenicity data against multiple patient-specific tumor targets in the first patients is a testimony of TG4050‘s potential and of the complementary synergies between the two companies. This milestone illustrates the central role of expanding the AI approach for individualized cancer immunotheraphy. As we previously stated, NEC and Transgene share a common goal to harness the power of data and develop new targeted therapies in oncology. We continue to be hopeful that TG4050 will make a significant difference in the lives of patients throughout the world,” commented Motoo Nishihara, Executive Vice President, CTO (Chief Technical Officer) and Member of the Board, NEC Corporation.

Prof. Christian H. Ottensmeier, MD, PhD, Professor of Immuno-oncology, at University of Liverpool and Prof. Jean-Pierre Delord, MD, PhD, General Manager of IUCT Oncopole of Toulouse, will share their insights on these early results in two upcoming webcasts, respectively in English and in French (see details at the end of the release).

TG4050 IS AN INDIVIDUALIZED NEOANTIGEN VACCINE TAILORED FOR EACH PATIENT.

This individualized immunotherapy is based on Transgene‘s advanced virus engineering platform myvac and NEC‘s deep expertise in artificial intelligence (AI). TG4050 is based on an MVA viral vector which is designed to educate the immune system against each patient’s most relevant tumor targets (up to 30 patient-specific neoantigens).These mutations are identified by next generation sequencing (NGS) and selected using NEC‘s proprietary AI-based immunogenicity prediction system. The main goal of the vaccine is to elicit a strong and long-lasting immune response against tumor antigens by targeting class I and class II epitopes. These two types of responses have been established as key factors in driving a sustained anti-tumor response.

DATA WERE GENERATED FROM 6 PATIENTS THAT HAVE BEEN TREATED WITH TG4050 ACROSS THE TWO PHASE I CLINICAL TRIALS.

The two studies are designed to assess biological and clinical activity of TG4050 given alone. In particular, the studies were designed to provide insights on the capacity of the selected target neoantigens to induce immune responses against these epitopes and, ultimately, to correlate clinical outcome with biological responses in two indications with significantly different genomic profiles.

The two Phase I clinical trials are exploring the activity of repeated injections of TG4050 as monotherapy in patients with minimal residual disease:

– In the ovarian cancer trial, patients receive the vaccine at first signs of asymptomatic relapse of their high grade, advanced-stage disease (after surgery and first-line chemotherapy). Asymptomatic relapse is defined as the detection of elevated CA-125 (tumor marker of ovarian cancer frequently associated with a relapse) or as low volume radiologic disease. The first patient was dosed in August 2020. Data have been generated from four patients treated in this trial.
– Patients with HPV-negative, advanced-stage head and neck cancer are at high risk of relapse after surgery and adjuvant therapy. In the trial, they are randomized after completion of this primary treatment to receive vaccination (early treatment arm) or to receive TG4050 at relapse (delayed vaccination arm). In this trial, the first patient was dosed in January 2021. As of today, six patients were randomized in this trial, two in the early treatment arm and four in the delayed vaccination arm.

Overall the data discussed today were obtained from the first six patients who received TG4050 across the two trials. The primary endpoints of these trials include safety and feasibility. Secondary endpoints include biological activity of the therapeutic vaccine TG4050.

CELLULAR IMMUNE RESPONSE WAS EVALUABLE FOR 4 OF THE PATIENTS TREATED WITH TG4050.

T-cell responses for each targeted mutation were assessed after 9 weeks of treatment with TG4050 and compared to baseline for the 4 patients for which evaluable samples were available. Neoepitope immunoreactive T-cells were quantified by ex vivo IFNgamma ELISPOT.

– All 4 patients developed a robust T-cell response against multiple targeted mutations (neoantigens) with a median of 10 positive responses per patient, confirming the capability of the AI to accurately select immunogenic neoantigens across the two selected indications.
– T-cell responses were observed for class I and class II epitopes. They consisted of de novo responses in 64% of observed responses (onset of response that were absent at baseline) and amplifications of preexisting responses for 36% of vaccine responses.
– Additionally, the development of these adaptive responses was concomitant with maturation and activation of the patients’ circulating immune cells, suggesting that the vaccine is able to effectively prime the immune system.

Compared to previously reported neoantigen studies, these data reinforce the rationale for TG4050‘s prediction system and support the validation of the MVA vector as an efficient platform for anti-tumor vaccination.

All immune assessments were conducted by the clinical immunology laboratory of Institut Curie (Paris).

FIRST SIGNALS OF CLINICAL ACTIVITY ARE EXTREMELY PROMISING FOR TG4050

In the ovarian cancer trial (n=4), one patient treated after an elevation of CA-125 experienced a normalization of CA-125 without clinical progression during 9 months until death from an unrelated chronic illness. Another patient with radiologic lesions is stable and is still under treatment with TG4050 9 months after the first injection.

In the head and neck trial early treatment arm (n=2), the two patients have been treated with TG4050 for 10 and 5 months respectively and are stable. Their treatment is ongoing.

To date, the vaccine has been well tolerated and no related Serious Adverse Events have been reported across the two studies. Adverse events are consistent with previous observations made with the MVA viral vector. They mainly consist of mild and transient symptoms, mostly injection site reactions.

HIGHLY ENCOURAGING DATA POINT TO BE SHARED WITH THE COMMUNITY AND BE SUPPORTED BY ADDITIONAL DATA.

Additional data will be generated in the coming months. Transgene expects to present them at a major oncology conference in 2022.

In both clinical studies, enrollment and patient dosing are progressing in line with our expectations. Overall, Transgene plans to enroll 13 patients in the ovarian cancer trial and 30 patients in the head and neck trial.

A conference call in English is scheduled on November 23, 2021, at 3:00 p.m. CET.
A conference call in French is scheduled on November 23, 2021, at 8:30 a.m. CET.
Replays will be available on the Transgene website (www.transgene.fr) following the live events.