The substantial molecular size of biologic therapeutics inherently restricts their tissue penetration. While antibodies can concentrate in tumors through cellular targeting mechanisms, these approaches inadequately capture soluble immune-inhibiting molecules. Intra-arterial administration of osmotic agents (25% mannitol with 4% saline) markedly enhances antibody delivery to vital organs, including the brain and tongue, addressing the critical challenge of insufficient antibody accumulation. This delivery strategy likely applies beyond antibodies and can be refined through radiolabeling and PET imaging of biological drug delivery. By improving the capture of soluble immunosuppressive factors within target tissues, this approach may unlock the full potential of anti-tumor immune responses.

CXCR4 is a well-studied chemokine receptor found upregulated in several cancers, yet developing therapeutic antibodies against it has proven challenging. The best-in-class antibody, Ulocuplumab, was discontinued in clinical development. Using the Salipro DirectMX technology to isolate wildtype CXCR4 together with the Bio-Rad Pioneer antibody discovery platform, novel CXCR4 antibodies were made with higher affinity and improved antagonistic properties compared to Ulocuplumab.

T cell engaging bispecific antibodies targeting CD3 have had notable success in treating hematologic tumors but have had limited efficacy in treating solid tumors. Employing safe and potency-optimized bispecific antibodies targeting immune co-stimulatory receptors may help overcome challenges related to solid tumors, such as the immuno-suppressive tumor microenvironment. Here, we describe our bispecific platforms and our lead program, RNDO-564, a CD28 x Nectin-4 bispecific antibody for treatment of metastatic bladder cancer.

Extra-domain B of fibronectin (EDB+FN) is an extracellular matrix (ECM) protein that is highly expressed in tumors with negligible expression in normal tissues. By targeting this non-cellular matrix protein, the ADC micvotabart pelidotin (MICVO/PYX-201) specifically localizes to the ECM within the tumor stroma where extracellular proteases cleave the linker releasing the payload which diffuses into and kills nearby cancer cells, resulting in the release of the payload to illicit the bystander effect as well as neoantigens to stimulate immunogenic cell death. The highly differential tumor expression of the non-cellular associated EDB+FN makes this protein a novel target for cancer therapy.

GV20 Therapeutics is a clinical-stage biotechnology company pioneering the integration of artificial intelligence (AI), genomics, and cancer immunology to develop novel cancer biotherapeutics. Their proprietary platform harnesses AI to decode patients' natural B cell responses from large cohorts of tumor profiles, enabling simultaneous discovery of novel targets and therapeutic antibodies. GV20's discovery pipeline spans best-in-class and first-in-class monoclonal and bispecific antibodies, as well as antibody-drug conjugates (ADCs), reflecting their comprehensive approach to innovative cancer therapy. 

Peptide-HLA (pHLA)-targeting therapeutics, including soluble T cell receptor (TCR) and TCR-mimic (TCRm) antibody-based therapeutics, drive potent and specific killing of infected and cancerous cells. However, these modalities require high affinity for efficacy in clinically validated formats, and native repertoires are pruned of high-affinity TCRs by the immune system. To overcome these barriers, we have generated fully antibody and TCR libraries in yeast, facilitating the rapid discovery and engineering of high-affinity soluble TCRs and TCRm antibodies, accelerating the preclinical development of potent and specific pHLA-targeting therapeutics.

Cyclic peptides with alternating tryptophan and arginine act as tyrosine kinase inhibitors and molecular transporters. To improve anticancer efficacy and reduce toxicity, these peptides were conjugated to doxorubicin (Dox). The conjugates retained potency in wild-type cells, showed enhanced activity in resistant cancer cells, and reduced heart and kidney toxicity. Mechanistic studies suggest they bypass efflux, improve nuclear delivery, and offer a promising approach to overcome Dox resistance with minimal cardiotoxicity.

Incretin analogs regulate appetite and insulin secretion and are used to treat diabetes and for weight management. Combination treatments will help counteract the loss of muscle mass associated with some analogs. To support the discovery and assessment of drug candidates, we developed a series of luciferase reporter cell lines measuring GLP-1R, GLP-2R, GIPR, GCGR, Activin, Leptin, and Amylin responses. Functionality was validated by quantifying agonist activity and EC50 determination of novel therapeutics.

We have developed SYN101, a first-in-class, non-cytotoxic ADC that selectively blocks TGF-b mediated immune suppression and drives tumor clearance in multiple tumor models in vivo. Our platform is enabled by our linkable TGF-b inhibitor payload, to improve safety, efficacy, and therapeutic window. Unlike systemic TGF-b inhibitors which cause heart toxicity, SYN101 is safe and does not cause tissue toxicity.

Peritoneal carcinomatosis (PC) is a devastating condition with limited treatment options. Interleukin-6 (IL-6) plays a critical role in PC progression by promoting inflammation and tumor growth. This research explores targeting IL-6 as a therapeutic strategy to disrupt these processes. Preclinical and clinical studies suggest that IL-6 inhibition may offer a promising approach to improve outcomes for patients with PC.