R3Mab

Our data demonstrate that increased HER3 is an effective therapeutic target for TNBC and our anti-HER3 mAb (4A7) may enhance the efficacy of gefitinib or paclitaxel in TNBC.

Potency of HMBD-001 to inhibit tumor growth as monotherapy or in combination with cetuximab and/or docetaxel was evaluated using murine CDX and PDX models. An analysis of copy number variations and expression of genes in Chr3q, Chr3p and Chr7p confirms that genes involved in HER3 signaling are frequently amplified and have higher expression in squamous compared to non-squamous NSCLC. Several genetic alterations in sqNSCLC lead to HER3 and EGFR pathway activation. HMBD-001, a potent anti-HER3 mAb, in combination with EGFR inhibition and chemotherapy, has the potential to greatly improve clinical outcomes following immune-chemotherapy. Hummingbird Bioscience plans to initiate Phase Ib clinical trials in biomarker selected populations of sqNSCLC in H2, 2023.

DM002 candidates showed robust anti-tumor activity in multiple CDX and PDX models of lung, breast, gastric and pancreatic cancer; most notably, DM002 candidates outperformed benchmark ADCs in BP0508 lung PDX models. Together, these data indicate that DM002 will be a promising therapeutic drug for patients with HER3 and MUC1 co-expressing tumors.

It is comprised of a bispecific antibody against EGFR/HER3 (SI-B001), a cathepsin B cleavable linker, and a novel topoisomerase I inhibitor agent (Ed-04), which is a derivative of the alkaloid camptothecin, driving cell cycle arrest at the S phase and subsequent apoptosis. The clinical phase I has been progressing and the available data exhibit excellent efficacy but low levels of targeted toxicity in the non-small cell lung cancer (NSCLC) treatment setting. Overall, these data suggest BL-B01D1 has potential to serve as a novel, efficacious therapeutic agent for NSCLC with similar therapeutic impact as DS-8201 has in breast cancer treatment.

These data extend previous findings in patients with EGFR m NSCLC and demonstrate promising clinical activity in patients with NSCLC harboring genomic alterations other than EGFR m and in those without identified driver genomic alterations. The overall safety profile was similar to that previously reported in patients with EGFR m NSCLC.

Receptor switching to other HER family members in Lapatinib resistance and HER2 receptor tyrosine kinase domain mutations have been elaborated in promoting resistance. BC cells over-expressing HER2-WT or S305C were found sensitive to Trastuzumab (P>0.001) or Neratinib (P>0.001), whereas cells with G309A, S310Y or P523S mutation were non-responder to those drugs as revealed by short-term, long-term viability, anchorage-independent growth and Immunoblot assessments. Conclusion The structural changes ensued after HER2 interaction domain mutations alters the downstream signalling cascades and impacts the therapy response to HER2 targeted medicines.

PACAP or NRG-1 increased the proliferation of NSCLC cells, whereas PACAP(6-38), gefitinib, trastuzumab, or mAb3481 inhibited proliferation. The results indicate that PAC1 regulates the proliferation of NSCLC cells as a result of transactivation of the EGFR, HER2, and HER3.

Since clinical testing of anti-HER3 monoclonal antibodies (mAbs) such as patritumab could not show remarkable effect compared with existing drugs, we generated novel mAbs against anti-HER3. Ab4 inhibited in vivo tumor growth of human colon cancer cells in nude mice. Present mAbs may be superior to existing anti-HER3 mAbs and support existing anti-cancer therapeutic mAbs.