GV20's STEAD platform leverages proprietary AI to decode the human immune system and uncover tumor targets and functional antibodies directly from patient tumor profiles. The power of STEAD is demonstrated by the unprecedented 3-year timeline from target research to IND of the lead program GV20-0251 against a novel immune checkpoint IGSF8, and validated by GV20-0251's favorable safety and promising monotherapy efficacy in advanced metastatic cancer patients in US clinics (NCT05669430). 

• STEAD application in ADC and bispecifics
• Antibody developability from AI-prediction
• STEAD for novel target discovery 
• Difference from AlphaFold AI
  

TfR1 shuttles show promise for Alzheimer's treatment, but toxicities remain limiting. Powered by AI and Manifold’s protein barcoding technology, we introduce a high-throughput  in vivo screening method to identify novel brain shuttles. Our approach reveals new shuttle targets and shuttles with diverse properties, particularly PX1, which enhances anti-Aß antibody delivery without the hematological toxicity of TfR1 shuttles. This work highlights the power of large-scale  in vivo testing.

HER3 overexpression is relatively common in breast- and other cancers, and the development of HER3-targeted drugs is therefore warranted. Affibody molecules are small engineered alternative scaffold affinity proteins that can be site-specifically loaded with cytotoxic drugs to create homogenous conjugates with a desired drug-to-affibody ratio. We have explored HER3-targeted affibody molecules loaded with the cytotoxic drug DM1 in xenograft models and determined their biodistribution and therapeutic potential.

• Designing ARTEMIS (AbTCR) T cell engineering technology to improve solid tumor T cell infiltration and reduce CRS
  
• Targeting Glypican 3 (GPC3) in advanced hepatocellular carcinoma (HCC)
  
• Preclinical and clinical data of GPC3-targeting ARTEMIS T cell therapy for HCC patients

VT1021, a cyclic peptide designed to stimulate thrombospondin-1 expression by replicating the biological activity of prosaposin, has been shown to stimulate TSP-1 production in the tumor microenvironment (TME). In the first-in-human study, the safety and tolerability, clinical response, and biomarker profile of VT1021 are reported. The modifications of the TME correlates with VT1021 treatment, from one that is immunosuppressive and tumor-promoting to one that is immune-active and tumor-inhibiting.

Calreticulin (CALR) mutations are responsible for MPNs in 20-30% of patients. Insertions or deletions CALR in exon 9 create positively charged C-terminus variants lacking the KDEL endoplasmic reticulum retention signal. Mutant CALR (mutCALR) transits with the thrombopoietin receptor (TPO-R) forming an extracellular neoantigen that constitutively activates the JAK2/STAT signaling. INCA033989 is an antibody targeting mutCALR, selective for cells expressing mutCALR that allows targeting neoplastic cells without compromising normal hematopoiesis.

Clonal mutations in driver genes such as TP53 and KRAS can be therapeutically targeted when mutated peptide fragments are presented on human leukocyte antigens (HLA). However, these neoantigens occur at extremely low numbers on the surface of cancer cells—often fewer than 10 per cell. Here, we describe the development of T cell receptor (TCR)-mimic antibodies and demonstrate their utility in chimeric TCRs for targeting a common TP53 neoantigen.

Human leukocyte antigen-G (HLA-G) is a target with high therapeutic potential, as it is involved in immunosuppression through interaction with ILT2 and ILT4. The high percent identity of HLA-G to other class I HLA molecules makes specific binding a crucial property of a therapeutic antibody. Here we present the discovery of an HLA-G-specific antibody (TTX-080) with our partner Tizona Therapeutics, and its development to a clinical program.

Most of the current targeted protein degradation approaches have focused on discovering new pathways for degradation and designing small molecule degraders against disease-relevant targets. Polymeric scaffolds have the potential to rather uniquely impact this vibrant field. This presentation will focus on the new frontiers in targeted protein degradation that are uniquely enabled by polymeric materials.

KRAS mutations are present in approximately 25% of all carcinomas. There are only two KRAS G12C inhibitors available. No treatment yet is available for cancers with other KRAS mutations, such as G12D, G13D, and G12V, which are more common subtypes. SBT-100 is a nano-antibody that inhibits STAT3 and KRAS mutations G12D and G13D, and wild KRAS. According to our preclinical studies, SBT-100 is a safe and well-tolerated pan-KRAS inhibitor. It effectively inhibits human cancers with KRAS mutations G12D and G13D. Although it has a short half-life in blood, it has a very long biological life.

ofCS is a carbohydrate expressed in the tumor microenvironment (stromal and cancer cells) in nearly all cancer types. It is also found in distant metastases and plays a role in immune evasion, making it an ideal target for antibody-based therapies. Our highly specific ofCS antibodies, functionalized into antibody drug conjugates, eradicated tumors in 10+ cancer models without recurrence or toxicity, underscoring the remarkable tumor-specificity of the ofCS carbohydrate molecule.

IL-21 is a critical cytokine that prevents T-cell exhaustion and enhances T-cell effector function. However, its clinical application in oncology is limited by its pleiotropic effects. To maximize IL-21's therapeutic potential, we developed AB821, a cis-targeted IL-21 designed to selectively activate CD8+ T cells. Preclinical data show that AB821 specifically targets antigen-experienced, exhausted CD8+ T cells in the tumor microenvironment with elevated IL-21R expression. Targeting these exhausted CD8+ T cells with AB821 reinvigorates their effector function, induces memory phenotypes, and drives profound anti-tumor effects in multiple PD1-refractory mouse tumor models.