BT-001 / BioInvent, Transgene - LARVOL DELTA

KEYNOTE-E37: A Clinical Trial Assessing BT-001 Alone and in Combination With Pembrolizumab in Metastatic or Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=31 | Terminated | Sponsor: Transgene | N=48 ➔ 31 | Trial completion date: Apr 2025 ➔ Oct 2025 | Recruiting ➔ Terminated | Trial primary completion date: Apr 2025 ➔ Oct 2025; Sponsor decision following completion of Phase I part not driven by safety reason

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Melanoma • Merkel Cell Carcinoma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Skin Cancer • Soft Tissue Sarcoma • Solid Tumor • Triple Negative Breast Cancer

Updated clinical results of BT-001, an oncolytic virus expressing an anti-CTLA4 mAb, administered in combination with pembrolizumab in patients with advanced solid tumors (ESMO 2025) - P1/2 | "Conclusions IT BT-001 injection in combo with IV pembrolizumab was well tolerated and showed encouraging and sustained anti-tumor activity in some patients with advanced refractory tumors. BT-001 could be an effective option to improve the response to ICI."

Clinical • Combination therapy • IO biomarker • Metastases • Oncolytic virus • Breast Cancer • Leiomyosarcoma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Triple Negative Breast Cancer • CSF2

BioInvent International AB…, Transgene…will jointly present a poster on translational data and updated clinical results from the Phase 1 study of BT-001 at the European Society for Medical Oncology (ESMO) Annual Meeting (BioInvent Press Release) - "Intra-tumoral BT-001 injection in combination with IV pembrolizumab was well tolerated with a manageable safety profile....One patient with PD(L)-1 resistant melanoma and one patient with heavily pretreated but ICI-naive leiomyosarcoma showed partial response (iPR) lasting 6 and 16 months respectively, among the 13 patients who received the combination of intra-tumoral BT-001 (at 107 pfu/mL and 108 pfu/mL) and pembrolizumab."

P1 data • Leiomyosarcoma • Melanoma

Transgene and BioInvent to Present Updated Data on Armed Oncolytic virus BT-001 at ESMO 2025 (BioInvent Press Release) - "BioInvent International AB...and Transgene...will jointly present a poster on updated data from the Phase 1 part of the Phase 1/2a study of BT-001 at the European Society for Medical Oncology (ESMO) Annual Meeting....The abstract will be available on ESMO’s website on October 13, 2025, at 00:05 CEST."

P1 data • Solid Tumor

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 (ESMO 2024) - P1/2 | "IT BT-001 alone or in combination with IV pembrolizumab was well tolerated and is showing early signals of activity in PD(L)1 refractory tumors. Preliminary translational data suggest that BT-001 is replicating in the tumor and that transgenes are expressed. Study is currently ongoing to further evaluate safety and activity."

Clinical • Combination therapy • Metastases • Oncolytic virus • Leiomyosarcoma • Melanoma • Oncology • Sarcoma • Solid Tumor • CSF2 • PD-L1

BioInvent and Transgene to Present Promising Initial Phase 1/2a Data on Oncolytic Virus, BT-001, at ESMO 2024 (BioInvent Press Release) - P1/2a | N=48 | NCT04725331 | Sponsor: Transgene | "BioInvent International AB...and Transgene...announce initial promising clinical results from the Phase 1 part of the ongoing Phase 1/2a trial of BT-001....Key findings of the abstract include: In the monotherapy part, in terms of overall response, stable disease was observed in 4/18 advanced solid tumor patients receiving BT-001 as single agent, while tumor shrinkage was observed in 2/20 injected lesions; In the combination part, two patients with partial responses were observed in a cohort of six heavily pretreated patients with advanced solid tumor receiving BT-001 in combination with pembrolizumab (one patient with a PD(L)-1 resistant melanoma and one patient with a leiomyosarcoma after five lines of therapy). Patient response profiles and updated results to be presented at ESMO."

P1 data • Leiomyosarcoma • Melanoma

BioInvent to Present Pipeline Progress on BI-1910 and BT-001 at ESMO (BioInvent Press Release) - "BioInvent International AB...announced abstracts for BI-1910 and BT-001 have been selected for presentation at ESMO 2024, being held in Barcelona, Spain from September 13th to 17th, 2024.....Two posters to be presented on early clinical projects from BioInvent’s robust pipeline totaling six clinical programs: (i) Progress with the Phase 1 trial studying BI-1910 as single agent in solid tumors; (ii) Initial clinical data from the BT-001 Phase 1 study evaluating the candidate both as single agent and in combination with KEYTRUDA (pembrolizumab) in patients with solid tumors."

P1 data • Trial status • Solid Tumor

Transgene anticipates significant progress from immunotherapy pipeline in 2024 and extends financial visibility until Q4 2025 (GlobeNewswire) - "Transgene has completed the enrollment of 86 patients in the ongoing randomized Phase II trial evaluating TG4001 in HPV-positive anogenital cancers (NCT03260023). Transgene confirms that top line readouts are expected in H2 2024....TG6050: Initial Phase I data expected in H2 2024, from this novel Invir.IO candidate administered intravenously....BT-001: Positive single agent data — Part B of the Phase I trial (combination with pembrolizumab) to deliver initial data in H2 2024."

P1 data • P1/2 data • Anal Carcinoma • Cervical Cancer • Melanoma • Merkel Cell Carcinoma • Non Small Cell Lung Cancer • Penile Cancer • Soft Tissue Sarcoma • Solid Tumor • Triple Negative Breast Cancer • Vulvar Cancer

Transgene and BioInvent - First Patient Treated in Part B of Phase I Trial Assessing the Novel Oncolytic Virus BT-001 in Combination With KEYTRUDA (pembrolizumab) (Businesswire) - "Transgene...and BioInvent International AB...announce that the first patient of the Phase I part B clinical trial evaluating the combination of BT-001 and MSD’s anti-PD-1 therapy, KEYTRUDA® (pembrolizumab) has been dosed. The Phase I Part B of the trial explores repeated intra-tumoral injections of BT-001 in combination with intravenous infusions of KEYTRUDA. Transgene and BioInvent plan to enroll a minimum of 12 patients with metastatic or advanced solid tumors, including melanoma....The inclusion of the last patient in Part B of the study is expected in H1 2024."

Trial status • Melanoma

Transgene Advances Its Innovative Immunotherapy Pipeline and Extends Financial Visibility Until the End of 2024 (Businesswire) - "Key events and upcoming milestones:...(i) TG4050:...The last patient has been randomized in the head and neck cancer Phase I study. Transgene and its partner NEC plan to report updated data in H1 2024. Transgene and NEC intend to start a randomized Phase II trial in the adjuvant setting of head and neck cancer in 2024.... (ii) BT-001...Part B of the Phase I trial (combination with pembrolizumab) to start in H2 2023."

New P2 trial • P1 data • Trial status • Head and Neck Cancer • Oncology • Solid Tumor

Transgene and BioInvent Report Positive Phase Ia Data on Oncolytic Virus BT-001 in Solid Tumors (Businesswire) - P1/2a | N=48 | NCT04725331 | Sponsor: Transgene | "Transgene...and BioInvent International AB...announce positive Phase Ia data on the oncolytic virus BT-001 for the treatment of solid tumors. Treatment with single agent BT-001 in 18 patients has now been completed with no safety concerns reported. Patients had at least one accessible superficial lesion and were studied in three dose-escalating cohorts. BT-001 stabilized the injected lesions in eleven patients in total: two at the 106 pfu dose (n=6), five at 107 pfu (n=6) and four at 108 pfu (n=6). Furthermore, objective antitumor activity, defined as decrease of injected lesion size of 50% or more, was observed in one patient in the 106 pfu cohort (n=6) and one patient in the 107 pfu cohort (n=6)....Based on these results, the independent Safety Review Committee (SRC) has now approved initiation of the combination part of the trial with pembrolizumab. The first patient in this Phase I part B is expected to be enrolled in H2 2023."

P1 data • Trial status • Oncology • Solid Tumor

Transgene: 2022 Full-year Results and Business Update (Businesswire) - "Summary of key ongoing clinical trials:...(i) TG4001 - Recurrent/metastatic anogenital HPV16-positive - 1st (patients ineligible for chemotherapy) and 2nd lines: Final results to be communicated in 2024; (ii) BT-001 - Solid tumors: Part A data to be communicated in H1 2023...Start of part B of the Phase I trial in H2 2023."

P1 data • P2 data • Trial status • Oncology • Solid Tumor

Bio4t2 announces first patient infused with CAR-T targeting solid tumors (PRNewswire) - "Bio4t2 dosed the first patient with T cells bearing a chimeric antigen receptor (CAR) that targets overexpression of BT-001 antigen present on various types of solid tumors. The CAR-T (B4t2-001) was developed from Bio4t2's PrismCore platform."

Trial status • Oncology • Solid Tumor

BioInvent Outlines Strong Progress in Clinical and Preclinical Pipeline at R&D Day 2022 (Yahoo Finance) - "BioInvent International AB...provides an update on its clinical and pre-clinical pipeline, including an update on its lead drug candidate, the novel anti-FcγRIIB antibody BI-1206....The ongoing clinical trial with BI-1206 in solid tumors is progressing through the dose-escalation part of the trial and the two patients reported last December still show clear clinical improvement. The subcutaneous arm of the study in solid tumors is on track to be initiated in H1 2023....The trial assessing BT-001 as a single agent and in combination with Keytruda against solid tumors is progressing well, and BioInvent and Transgene plan to present results from Part A at a scientific conference H1 2023."

P1/2 data • Trial status • Breast Cancer • Lung Cancer • Melanoma • Merkel Cell Carcinoma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Skin Cancer • Soft Tissue Sarcoma • Solid Tumor • Triple Negative Breast Cancer

Transgene and BioInvent Joint Paper on BT-001 Wins JITC “Best Oncolytic and Local Immunotherapy Paper” Award for 2022 (Businesswire) - "Transgene...and BioInvent International AB...announced that a paper co-authored by researchers from Transgene and BioInvent is the recipient of this year’s Journal for ImmunoTherapy of Cancer (JITC) 'Best Oncolytic and Local Immunotherapy Paper' Award. The paper on BT-001 was highlighted at the annual Society for Immunotherapy of Cancer (SITC) conference being held November 8-12, 2022 in Boston, MA."

P1/2 data • Oncology • Solid Tumor

Positive Readouts for Transgene’s Clinical Stage Candidates Generated by its Two Innovative Platforms, with Further Clinical Data Expected in the Second Half of 2022 (Businesswire) - "TG4001 – Results from the interim analysis of the randomized Phase II trial in HPV-positive anogenital cancers to be released in Q4 2022; TG4050 (myvac® platform) – New positive Phase I data presented at AACR and ASCO - Additional data from the two Phase I trials to be communicated in H2 2022; TG6002 – Phase I data confirming the potential of the intravenous administration of Transgene’s Invir.IO™ oncolytic viruses will be presented at ESMO 2022 on September 11 at 12 pm CET; BT-001 (Invir.IO™ platform) – Initial Phase I data demonstrated good tolerability and first signs of antitumor activity - Phase Ib (BT-001 in combination with pembrolizumab) expected to start in the second half of 2022."

P1 data • P2 data • Anal Carcinoma • Gastrointestinal Cancer • Gynecologic Cancers • Head and Neck Cancer • Oncology • Ovarian Cancer • Solid Tumor

A Clinical Trial Assessing BT-001 Alone and in Combination With Pembrolizumab in Metastatic or Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=48 | Recruiting | Sponsor: Transgene | Trial completion date: Nov 2024 ➔ Apr 2025 | Trial primary completion date: Nov 2024 ➔ Apr 2025

Combination therapy • Trial completion date • Trial primary completion date • Breast Cancer • Lung Cancer • Melanoma • Merkel Cell Carcinoma • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Non-melanoma Skin Cancer • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Triple Negative Breast Cancer

Transgene and BioInvent Announce Clinical Trial Collaboration and Supply Agreement with MSD to Evaluate BT-001 in Combination with KEYTRUDA (Businesswire) - "Transgene...and BioInvent International AB...announced a clinical trial collaboration and supply agreement with MSD, a tradename of Merck & Co., Inc., Rahway, NJ., USA, to evaluate the oncolytic virus BT-001 in combination with MSD’s anti-PD-1 therapy KEYTRUDA® (pembrolizumab) in a Phase I/IIa clinical trial for the treatment of patients with solid tumors. Under the terms of the supply agreement, MSD will provide pembrolizumab to be used in combination with BT-001 in the ongoing Phase I/IIa clinical trial....Recruitment in the clinical study (NCT04725331) is ongoing. The trial is a Phase I/IIa of BT-001, which is being co-developed as part of a 50/50 collaboration between Transgene and BioInvent, as a single agent and in combination with KEYTRUDA® for the treatment of solid tumors."

Licensing / partnership • Trial status • Oncology • Solid Tumor

Transgene and BioInvent Announce Positive Progress for BT-001 (Businesswire) - P1/2 | N= 48 | NCT04725331 | Sponsor: Transgene | "Transgene...and BioInvent International AB...jointly announced positive progress and safety data of the ongoing Phase I/IIa trial evaluating BT-001 in patients with solid tumors, including melanoma. The initial data generated in Phase I part A demonstrated that BT-001 alone is well tolerated...The initial findings are as follows: (i) After administration, the virus was found in the tumors after several days. This suggests that BT‑001 is able to persist and replicates within tumors; (ii) This finding is consistent with the expression of the anti-CTLA-4 observed in the tumor with no detectable systemic exposure; (iii) No spreading in blood or biological fluids has been detected, suggesting high tumor specificity; (iv) Tumor shrinkage was observed in one patient in the first cohort....The first two dose levels have been successfully completed, with 12 patients dosed to date....The Phase I part B is planned to start in H2 2022."

P1 data • Trial status • Melanoma • Oncology • Skin Cancer • Solid Tumor

"$BINV Transgene and BioInvent Announce Positive Progress for BT-001 https://t.co/FEYdVJVhGx" (@stock_titan)

Comprehensive preclinical studies of BT-001: An oncolytic vaccinia virus armed with Treg-depleting @CTLA4 and GM-CSF (AACR 2022) - "This vector-based delivery is a highly effective and safe strategy to target CTLA-4 which overcomes current limitations of approved αCTLA-4 regimens. A clinical trial evaluating i.t. VVGM-αhCTLA4 (BT-001) alone and in combination with αPD-1 in metastatic or advanced solid tumors has been initiated."

Oncolytic virus • Preclinical • Oncology • Solid Tumor • CD8 • CSF2 • CTLA4

Better Therapeutics Announces Key Milestones and Updates for Ongoing Studies of its Digital Therapeutics Approach for Cardiometabolic Diseases (BioSpace) - '"With a quarter of American adults affected by NAFLD, including 70% of diabetes patients, fatty liver disease is a growing public health crisis made even more challenging by a lack of effective, FDA-approved therapeutics,' said Mazen Noureddin, MD...'We are hopeful that the nCBT approach offered by Better Therapeutics can prove effective in treating this condition and alleviating the pressure it places on our health system, including the $100 billion annual cost incurred as a direct result of this condition.'"

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Transgene Confirms the Potential of Its Two Innovative Platforms and Expects Significant Clinical Results in 2022 (Businesswire) - "TG4050 (myvac): Additional data to be presented at AACR 2022 in April...TG4001: Interim analysis expected in Q4 2022.... BT-001 (Invir.IO): IND approval for Phase I/IIa trial in the US, ongoing enrollment in Europe...The next clinical update on the ongoing Phase I trial is expected in the second quarter of 2022...TG6002: End of Phase I expected in mid-2022....The Phase I trial evaluating TG6002 administered intravenously is expected to be completed by mid-2022. Comprehensive translational data will be presented in the fourth quarter of 2022."

IND • P1 data • P1/2 data • Anal Carcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Transgene and BioInvent Announce Poster Presentation on BT-001, a Novel Antibody-encoding Oncolytic Virus, at AACR 2022 (Businesswire) - “Transgene…and BioInvent International AB…jointly announce that an abstract reporting preclinical studies of BT-001, a novel oncolytic virus, has been selected for a poster presentation at the American Association for Cancer Research (AACR) Annual Meeting 2022. The conference will be held in person in New Orleans, LA, April 8-13, 2022. The preclinical data to be presented demonstrate that vectorized anti-CTLA-4 antibodies delivered intratumorally (i.t.) can improve safety by reducing their systemic exposure. Efficacy may also be improved, with evidence from the immunocompetent murine model showing that vectorized anti-CTLA-4 antibodies have anti-tumoral activity even against ‘cold tumors’ that are resistant to systemically-delivered checkpoint inhibitors.”

Preclinical • Oncology • Solid Tumor

Vectorized Treg-depleting αCTLA-4 elicits antigen cross-presentation and CD8 T cell immunity to reject 'cold' tumors. (PubMed, J Immunother Cancer) - "The identified 4-E03 antibody showed significantly stronger Treg depletion, but equipotent checkpoint blockade, compared with clinically validated αCTLA-4 ipilimumab against CTLA-4-expressing Treg cells in a humanized mouse model in vivo. Our findings demonstrate in vivo proof of concept for spatial restriction of Treg depletion-optimized immune checkpoint blocking, vectorized αCTLA-4 as a highly effective and safe strategy to target CTLA-4. A clinical trial evaluating intratumoral VV-αhCTLA-4 (BT-001) alone and in combination with αPD-1 in metastatic or advanced solid tumors has commenced."

Journal • Immune Modulation • Inflammation • Oncology • Solid Tumor • CD8 • CSF2