CEO.CA Chairman's Briefing

The publication reports results from the monotherapy dose-escalation portion of BioInvent's ongoing Phase 1/2a clinical trial (NCT04752826) of BI-1808 in patients with advanced solid tumors. BI-1808 is a fully human, ligand-blocking, Fcγ receptor-engaging anti-TNFR2 antibody designed to enhance anti-tumor immunity through multiple complementary mechanisms.

Patients with advanced solid tumors who progress after standard therapy have few remaining options, and checkpoint blockade leaves many tumor types, particularly non-inflamed or cold tumors, largely untreated. TNFR2 is highly upregulated in the tumor microenvironment and is expressed on the most immunosuppressive tumor-associated myeloid cells and Tregs. BI-1808 is a first-in-class, ligand-blocking, FcγR-engaging anti-TNFR2 antibody designed to deplete these Tregs, reprogram myeloid cells, and induce CD8+ T cell antitumor immunity.

The published data show that this mechanism, established in preclinical models, translates to treated patients. The mechanism itself was characterized in a recent complementary paper in AACR's sister journal, Cancer Research, titled "Ligand-Blocking and Agonist Antibodies Targeting TNFR2 Employ Distinct Modes of Action to Induce Antitumor Immunity." DOI: 10.1158/0008-5472.CAN-26-0274

"Our findings provide the first clinical validation of TNFR2 as an immunotherapy target and demonstrate that BI-1808 can safely induce broad immune activation through mechanisms distinct from existing checkpoint inhibitors," said Andres McAllister, Chief Medical Officer at BioInvent and co-senior author of the publication. "Particularly encouraging is the evidence of anti-tumor activity in a patient with GIST, a tumor type that rarely responds to current immunotherapies, supporting the potential of BI-1808 to expand the reach of immunotherapy to patients with non-inflamed cancers."

Björn Frendéus, Chief Scientific Officer at BioInvent and co-senior author, added: "The translational data demonstrate remarkable consistency between our preclinical findings and the observations in patients. The combination of strong biological activity, preliminary clinical responses and an excellent safety profile reinforce our belief that BI-1808 is well positioned for development both as a monotherapy and in combination with checkpoint inhibitors, antibody-drug conjugates, targeted therapies and other treatment modalities."

Publication Details
Title: Anti-TNFR2 antibody BI-1808 induces tumor regression and antitumor T cell immunity through T reg and myeloid cell modulation in patients with solid tumors: a preclinical and phase 1 clinical study
Lead Author: Ingrid Teige, PhD, BioInvent International AB
Journal: Clinical Cancer Research, https://aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-26-2049

The publication presents the first clinical evidence that targeting TNFR2 can generate anti-tumor immunity by coordinately modulating regulatory T cells and myeloid cells, leading to intratumoral CD8+ T cell infiltration and activation. Alongside evidence of stimulation of tertiary lymphoid structure formation and of safe, well-tolerated administration at pharmacologically optimal doses, these observations support continued development of BI-1808 across solid tumors and T-cell malignancies.

Study Design and Patients

• 24 patients treated across five cohorts (25, 75, 225, 675, and 1000 mg every three weeks), enrolled January 2021 to April 2023; 21 evaluable for efficacy
• Median 3 prior lines of therapy (range 0 to 12); all patients progressed on prior treatment; 8 patients (33%) had received prior immunotherapy

Evidence of Clinical Activity

• Tumor regression in 2 of 21 evaluable patients
• GIST patient: partial response lasting more than two years, continuing through compassionate use; biopsies at weeks 16 and 82 contained no tumor cells
• NSCLC patient: all three target lesions reduced at week 16; withdrawn per protocol following detection of an unrelated prostate cancer lesion; best response recorded as stable disease
• Neither patient with tumor regression had received prior anti-PD-1 or anti-CTLA-4
• Stable disease best response in six additional patients

Favorable Safety and Tolerability

• No maximum tolerated dose reached
• No deaths, no dose-limiting toxicities, no immune-related adverse reactions above Grade 2
• All treatment-related adverse events Grade 1 or Grade 2
• No discontinuations or dose reductions due to drug-related adverse events
• Infusion-related reactions in 2 patients at 1000 mg (Grade 1 chest pain, Grade 2 chills), both resolved the same day
• No confirmed anti-drug antibody-positive samples across 24 patients

Mechanistic Validation of BI-1808 and TNFR2 Targeting

• Dose-dependent Treg depletion at all dose levels, sustained at 1000 mg
• Increased monocyte CD16 expression
• Dose-dependent serum increases in CCL22, CXCL10, IL-12p40, and CCL19
• Cytokine kinetics in patients matched those in murine BI-1808 surrogate (3F10)-treated tumor-bearing mice
• GIST patient: circulating CX3CR1+ CD8+ T cells rose at day 50, before imaging showed regression; paired biopsies showed an increased CD8+ T cell to Treg ratio
• No baseline difference in TNFR2 expression or tumor inflammation between the two regressing patients and the rest

Pharmacokinetics and Dose

• Mean estimated half-life approximately 9 days
• Sustained TNFR2 receptor occupancy at doses of 675 mg and above
• 1000 mg every three weeks selected as recommended Phase 2 dose

About the trial
The BI-1808 study (NCT04752826) is an ongoing open-label, dose-escalation Phase 1/2a study evaluating BI-1808 as a single agent and in combination with pembrolizumab. The publication reports on the monotherapy Phase 1 dose-escalation portion, where patients were enrolled at nine study locations in Europe.

About BI-1808
BI-1808 is a first-in-class drug candidate targeting TNFR2. TNFR2 is upregulated on both immunosuppressive and inflammatory tumor-infiltrating lymphocytes (TILs) and on myeloid cells in the tumor microenvironment, making it a dynamic, promising new target for cancer immunotherapy. BI-1808 is in clinical development for T-cell lymphoma and solid tumors. BI-1808 has shown single-agent activity and excellent tolerability in an ongoing Phase 2a study and efficacy and a favorable safety profile in combination with pembrolizumab in an ongoing Phase 1/2a study.

BI-1808 has received FDA Fast Track Designation for the treatment of ovarian cancer and for relapsed or refractory mycosis fungoides and Sézary syndrome, FDA Orphan Drug Designation for T-cell lymphoma, and a positive opinion from the European Medicines Agency for Orphan Drug Designation in cutaneous T-cell lymphoma.

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 drug candidates in ongoing clinical programs in Phase 1/2 trials for the treatment of solid tumors and hematological cancer. 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 immune-modulatory 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 on the Company's website.

For further information, please contact:
Cecilia Hofvander, VP Investor Relations
Phone: +46 (0)46 286 85 50
Email: cecilia.hofvander@bioinvent.com

BioInvent International AB (publ)
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Phone: +46 (0)46 286 85 50
www.bioinvent.com

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.

Attachments

BioInvent Announces Publication of First-in-Human BI-1808 Data in Clinical Cancer Research