Transgene and BioInvent Joint JITC Publication Demonstrates the Potential of BT-001 Oncolytic Virus to Provide Therapeutic Benefit Beyond Current Anti-PD1/ Anti-CTLA-4 Immune Checkpoint Blockade

Rhea-AI Summary

Transgene and BioInvent announced in a press release that their co-developed product, BT-001, has shown promising preclinical proof-of-concept data, published in the Journal for ImmunoTherapy of Cancer. The study indicates that BT-001 may provide superior therapeutic benefits over conventional anti-CTLA-4 antibodies, with significant reductions in systemic toxicity and enhanced efficacy against ‘cold tumors’. Ongoing Phase 1/2a trials in Europe aim to demonstrate BT-001's effectiveness against solid tumors, with initial data expected in H1 2022.

Positive

• Promising preclinical data published in a respected journal.
• BT-001 shows potential to outperform conventional anti-CTLA-4 antibodies.
• Reduced systemic toxicity with improved efficacy against cold tumors.
• Ongoing Phase 1/2a clinical study progressing steadily.

Negative

• None.

Preclinical proof-of-concept data published in the January 20, 2022 edition of the Journal for ImmunoTherapy of Cancer (JITC).

STRASBOURG, France & LUND, Sweden--(BUSINESS WIRE)-- Regulatory News:

Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapeutics against cancer, and 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, today jointly announced the publication of extensive preclinical proof-of-concept data for BT-001 in the Journal for ImmunoTherapy of Cancer (JITC). This peer-reviewed article demonstrates that their co-developed clinical stage product, based on Transgene’s patented oncolytic vector and encoding BioInvent’s proprietary anti-CTLA-4 antibody, has the potential to provide greater therapeutic benefit than systemically administered anti-CTLA-4 antibodies.

Systemically administered anti-CTLA-4 antibodies, such as the approved ipilimumab, have demonstrated substantial efficacy but also clinically-limiting toxicity.

The JITC paper provides in vivo evidence 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. Furthermore, the precise targeting of the antibody to a unique functional epitope of CTLA-4 provides a higher level of regulatory T cells (Treg) depletion than ipilimumab.

“This strong preclinical data supports the development of our oncolytic virus BT-001 as an effective agent to treat solid tumors. We have vectorized a uniquely targeted anti-CTLA-4 antibody for intratumoral delivery and shown in vivo evidence that this reduces systemic toxicity, addresses ‘cold tumors’ and provides excellent tumor-selective Treg depletion. We are keenly anticipating progress in our ongoing Phase 1/2a clinical study with BT-001,” said Bjorn Frendéus, Chief Scientific Officer of BioInvent.

“These data demonstrate the relevance of the approach which is based on combining our respective technologies to fully exploit the synergy between oncolytic vector, targeted delivery of a potent payload targeting immunosuppressive cells, and recruitment of effector T cells. The antitumor properties showed in this JITC publication give us great confidence in the results we expect from the further clinical development of BT-001,” added Éric Quéméneur, Executive VP & Chief Scientific Officer of Transgene.

The safety-relevant data, published in JITC, show that a murine vector version of BT-001 delivered sustained levels of CTLA-4-receptor-saturating antibodies within tumors but low, sub-saturating exposure in blood and the non-tumor tissue. These antibody levels were associated with high depletion of Tregs in the tumor but the absence of systemic Treg depletion, notably in the spleen.

The study also provides several key insights into likely mechanisms underlying the efficacy of BT-001. Vectorized anti-CTLA-4:

• triggered both Fcγ-receptor-dependent Treg depletion and antigen cross-presentation, mechanisms known to trigger and promote long-lasting, systemic, CD8+ T cell antitumor immunity;
• showed broad antitumor activity, including activity against murine ‘cold tumor’ models which are resistant to systemic checkpoint inhibitors;
• showed additive or synergistic anti-tumor activity when combined with anti-PD-1.

The JITC paper is titled “Vectorized Treg-depleting αCTLA-4 elicits antigen cross-presentation and CD8+ T cell immunity to reject ‘cold’ tumors” and can be accessed here.

Recruitment in the ongoing Phase I/IIa clinical study of BT-001 (NCT04725331) in Europe is progressing steadily. The trial assesses BT-001 as a single agent and in combination with the PD-1 checkpoint inhibitor pembrolizumab against solid tumors. Initial Phase I data are expected in the first half of 2022.

About BT-001

BT-001 is an oncolytic virus generated using Transgene’s Invir.IO™ platform and its patented large-capacity VV_copTK^-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 will 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 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 two therapeutic vaccines (TG4001 for the treatment of HPV-positive cancers, and TG4050, the first individualized therapeutic vaccine based on the myvac® platform) as well as two oncolytic viruses (TG6002 for the treatment of solid tumors, and BT-001, the first oncolytic virus based on the Invir.IO™ platform).

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. Transgene has an ongoing Invir.IO™ collaboration with AstraZeneca.

Additional information about Transgene is available at: www.transgene.fr.

Follow us on Twitter: @TransgeneSA

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 three drug candidates in four ongoing clinical programs in Phase l/ll trials for the treatment of hematological cancer and solid tumors, respectively. The Company’s validated, proprietary F.I.R.S.T™ technology platform simultaneously 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 or for additional licensing and partnering.

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 us on Twitter: @BioInvent

Transgene disclaimer

This press release contains forward-looking statements, which are subject to numerous risks and uncertainties, which could cause actual results to differ materially from those anticipated. The occurrence of any of these risks could have a significant negative outcome for the Company’s activities, perspectives, financial situation, results, regulatory authorities’ agreement with development phases, and development. The Company’s ability to commercialize its products depends on but is not limited to the following factors: positive pre-clinical data may not be predictive of human clinical results, the success of clinical studies, the ability to obtain financing and/or partnerships for product manufacturing, development and commercialization, and marketing approval by government regulatory authorities. For a discussion of risks and uncertainties which could cause the Company’s actual results, financial condition, performance or achievements to differ from those contained in the forward-looking statements, please refer to the Risk Factors (“Facteurs de Risque”) section of the Universal Registration Document, available on the AMF website (http://www.amf-france.org) or on Transgene’s website (www.transgene.fr). Forward-looking statements speak only as of the date on which they are made, and Transgene undertakes no obligation to update these forward-looking statements, even if new information becomes available in the future.

BioInvent disclaimer

The press release contains statements about the future, consisting of subjective assumptions and forecasts for future scenarios. Predictions for the future only apply as the date they are made and are, by their very nature, in the same way as research and development work in the biotech segment, associated with risk and uncertainty. With this in mind, the actual outcome may deviate significantly from the scenarios described in this press release.

View source version on businesswire.com: https://www.businesswire.com/news/home/20220119005975/en/

Transgene:

Jean-Philippe Del

Chief Financial Officer

+33 (0)3 88 27 91 00

investorrelations@transgene.fr

Media: MEDiSTRAVA Consulting

David Dible/Sylvie Berrebi

+44 (0)7714 306525

transgene@medistrava.com

BioInvent:

Cecilia Hofvander

Senior Director Investor Relations

+46 (0)46 286 85 50

cecilia.hofvander@bioinvent.com



BioInvent International AB (publ):

Co. Reg. No. Org nr: 556537-7263

Visiting address: Ideongatan 1

Mailing address: 223 70 LUND

Phone: +46 (0)46 286 85 50

www.bioinvent.com

Source: Transgene

FAQ

What are the key findings from the BT-001 study published on January 20, 2022?

The study found that BT-001 may provide greater therapeutic benefits than traditional anti-CTLA-4 antibodies, with reduced systemic toxicity and enhanced effectiveness against cold tumors.

How does BT-001 improve safety compared to conventional treatments?

BT-001 minimizes systemic exposure by delivering the anti-CTLA-4 antibody intratumorally, which leads to reduced systemic toxicity.

What is the status of the ongoing clinical trials for BT-001?

The Phase 1/2a clinical study of BT-001 is progressing steadily, with initial data expected in the first half of 2022.

What does the collaboration between BioInvent and Transgene involve?

The collaboration focuses on the co-development of BT-001, utilizing Transgene's oncolytic vector technology and BioInvent's antibody expertise.

What is the potential impact of BT-001 on treating solid tumors?

BT-001 aims to enhance treatment efficacy against solid tumors, particularly those resistant to existing therapies, by improving tumor-selective Treg depletion.