- A new payload class: RVU602 is a proprietary, potentially first-in-class ADC payload with a mechanism of action orthogonal to both topoisomerase I (TOPO1) inhibitors and microtubule inhibitors – the two payload classes behind nearly all approved and late-stage ADCs.
- Designed to overcome key limitations of current ADCs: RVU602 is essentially unaffected by P-gp-mediated drug efflux, retains activity in TOPO1 inhibitor-resistant models, and has the potential to induce immunogenic cell death.
- Strong in-vivo proof of concept: a sacituzumab-based (anti-TROP2) RVU602 ADC achieved complete responses in 100% of animals at 10 mg/kg once weekly in the HCC70 triple-negative breast cancer (TNBC) xenograft model.
- Broad applicability: RVU602 was successfully conjugated to four clinically validated antibodies (anti-TROP2, anti-EGFR, anti-c-MET and anti-HER2), yielding stable ADCs with sub-nanomolar potency and complete tumor cell killing in-vitro.
KRAKOW, Poland, October 15, 2026 / Biotech Newswire / -- Ryvu Therapeutics (WSE: RVU), a clinical-stage drug discovery and development company focused on novel therapies that address emerging targets in oncology, presents preclinical in-vivo data on ADCs based on RVU602, its proprietary novel ADC payload, at the World ADC Congress, October 12-15, 2026, in San Diego, CA.
Nearly all approved and late-stage antibody-drug conjugates (ADCs) rely on just two payload classes: microtubule inhibitors (e.g., MMAE) and topoisomerase I inhibitors (e.g., DXd, SN-38). Shared mechanisms mean shared failure modes: tumors progressing on one TOPO1 inhibitor-based ADC often cross-resist to the next, drug efflux transporters such as P-gp blunt activity, and overlapping toxicities limit sequencing and combinations. As the antibody targets of the leading ADCs become increasingly crowded, the next gains in ADC performance are expected to come from novel payloads.
RVU602 was discovered on Ryvu’s payload discovery platform, which combines patient-derived models, high-throughput phenotypic screening and transcriptomic mechanism-of-action profiling with in-house medicinal chemistry optimized for potency, efflux resistance and conjugation-ready stability. The data presented at the World ADC Congress show that RVU602 addresses four unmet needs in a single payload: activity in TOPO1 inhibitor-resistant disease, no efflux liability, an orthogonal mechanism of action and built-in immunomodulatory potential.
Krzysztof Brzózka, Ph.D., Chief Scientific Officer of Ryvu Therapeutics, said: "RVU602 is the first payload from our ADC discovery platform and a strong validation of our phenotypic, patient-derived approach to payload discovery. Rather than optimizing yet another topoisomerase or tubulin inhibitor, we set out to find a genuinely new mechanism. RVU602 not only kills tumor cells that are resistant to today’s leading ADC payloads, but also triggers immunogenic cell death, which opens the door to rational combinations with immunotherapy. Complete responses in all animals treated with our TROP2-directed ADC are a very encouraging in-vivo proof of concept."
Paweł Przewięźlikowski, Chief Executive Officer of Ryvu Therapeutics, said: "Less than two years after launching our first in-house ADC program, supported by non-dilutive funding, we are presenting in-vivo proof-of-concept data for a proprietary first-in-class payload that we believe can differentiate next-generation ADCs. Novel payloads are attracting significant interest in ADC partnering. RVU602 adds a new, platform-type opportunity to Ryvu’s portfolio, which we intend to advance towards partnering, while we continue to progress our clinical programs."
Details on the poster presentation are as follows:
Poster Title: RVU602: A Non-TOPO1/Non-Tubulin Payload for Next-Generation ADCs
Poster Number: 96
Session date and time: Wednesday, October 14, 2026, 10:00 AM PDT (7:00 PM CEST)
What differentiates the RVU602 payload
- A third mechanistic class. Transcriptomic profiling shows that RVU602 induces neither the replication-stress signature characteristic of TOPO1 inhibitors nor the mitotic-arrest signature of tubulin inhibitors. This opens the option of sequencing RVU602-based ADCs after, or combining them with, DXd- and MMAE-based ADCs.
- Active in TOPO1 inhibitor-resistant tumors. In cells carrying a TOPO1 mutation, deruxtecan (DXd) lost more than 100-fold potency, whereas RVU602 retained full activity (resistant/parental EC50 ratio of 1.0-4.4). This is directly relevant for the growing population of patients progressing on TOPO1 inhibitor-based ADCs.
- No efflux liability. In a P-gp-high cell line, RVU602 potency was essentially unaffected by P-gp inhibition (1.6-fold shift, versus 3.7-fold for DXd and 12-fold for MMAE), indicating that RVU602 overcomes a major efflux-driven resistance route.
- Built-in immunomodulatory activity. Beyond direct cytotoxicity, RVU602 induces the release of extracellular ATP, a hallmark of immunogenic cell death, supporting the potential of RVU602-based ADCs in combination with immune checkpoint blockade.
- Deep, pan-tumor cytotoxicity. Across a panel of 272 cancer cell lines, RVU602 showed broad cytotoxic activity and a markedly deeper response than DXd.
ADC validation and in-vivo proof of concept
- RVU602 was conjugated to four antibodies – sacituzumab (anti-TROP2), cetuximab (anti-EGFR), telisotuzumab (anti-c-MET) and trastuzumab (anti-HER2). The resulting ADCs showed high monomeric content (>95%), high drug-to-antibody ratios (DAR 6-8) and low payload release in plasma (<1% in mouse and <15% in human plasma after 7 days).
- RVU602 ADCs combined sub-nanomolar potency with complete tumor cell killing in-vitro, outperforming datopotamab deruxtecan (Dato-DXd) and matching a cetuximab-MMAE comparator.
- In patient-derived TROP2-positive TNBC cells, the RVU602 ADC achieved low-nanomolar potency (EC50 0.4-7.5 nM) with 100% efficacy and 30- to 250-fold selectivity over the isotype control, supporting its translational potential.
- In the TROP2-positive HCC70 TNBC xenograft model, the sacituzumab-RVU602 ADC led to complete responses in 100% of animals after two doses at 10 mg/kg once weekly (QW) and in 83% of animals after four doses at 5 mg/kg twice weekly (BIW). Strong target engagement in tumors correlated with tumor growth inhibition. Sacituzumab govitecan (20 mg/kg QW) was included as a reference arm.
Together, these data validate RVU602 across multiple antibody targets and models, including settings resistant to topoisomerase I inhibitors, and support RVU602 as a differentiated payload for next-generation ADCs.
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About ADCs
Antibody-drug conjugates (ADCs) represent an advanced targeted therapy that combines a small-molecule drug with a monoclonal antibody. The antibody selectively binds to a specific antigen on the surface of cancer cells, ensuring the precise delivery of the cytotoxic agent to the tumor, while minimizing damage to healthy tissues. An ADC consists of three key components: a monoclonal antibody that accurately targets cancer cells, a cytotoxic payload (active substance) that destroys the tumor, and a linker that ensures controlled drug release at the intended site.
About Ryvu Therapeutics
Ryvu Therapeutics is a clinical-stage drug discovery and development company focused on novel therapies that address emerging targets in oncology. Internally discovered pipeline candidates at Ryvu use diverse therapeutic mechanisms driven by emerging knowledge of cancer biology, including small molecules and antibody-drug conjugates directed at kinases, synthetic lethality, and immuno-oncology targets.
Ryvu's most advanced program is romaciclib (RVU120, SEL120), a selective CDK8/CDK19 kinase inhibitor with the potential to treat hematological malignancies and solid tumors. Romaciclib is currently in Phase II development in combination with venetoclax for the treatment of patients with r/r AML – the RIVER-81 study – and is also being evaluated in an investigator-initiated Phase I study in pediatric medulloblastoma – the MEDWAY study. Dapolsertib (MEN1703, SEL24) is a dual PIM/FLT3 kinase inhibitor licensed to the Menarini Group, currently being investigated in a Phase II study in diffuse large B-cell lymphoma (DLBCL) – the JASPIS-01 study – with a further Phase II study in myelofibrosis (SPHENE-01) planned to start in Q1 2027. RVU305, a potentially best-in-class, brain-permeable PRMT5 inhibitor aiming to treat multiple solid tumors, has completed IND/CTA-enabling studies. Ryvu Therapeutics is also engaged in oncology collaborations with BioNTech and Exelixis, and offers dedicated early clinical development services to biotech and pharma partners through its Keelira business.
Ryvu was founded in 2007 and is headquartered in Kraków, Poland. It is listed on the Warsaw Stock Exchange and is a component of the sWIG80 index.
Contact
Ryvu Therapeutics
Anna Wilk
+48 532 698 425
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Source: Biotech Newswire