TTX 335o Oncology

Novel Targeted Treatment for Recurrent, Sensitive and Platinum Resistant Ovarian Cancer

History

The discovery emerged serendipitously from our academic collaborator's (Dr. Ghassan Saed at Wayne State University and Karmaos Cancer Center) original provocative finding that a cell surface marker, previously only thought to be expressed on immune cells, was expressed in epithelial ovarian cancer (EOC) cells and tissues.  He later published these results.

Replication/Duplication by Multiple Labs

Rigorous in vitro and in vivo testing of numerous ovarian as well as other cancer cell lines with various sources of the antibody reproducibly demonstrated its remarkable cell killing effect with abnormally growing cells. More importantly, the antibody did not kill normal ovarian surface epithelial cells, nor did it kill macrophages, which are known to express excessive amounts of the myeloid antigen.  This work has now been replicated by three other independent labs.

Temple and its Consortium Partners Win $3M Eurostars Grant (2019) 

The novelty, targeted therapy and potential treatment for one of the deadliest diseases affecting women, earned a highly competitive and prestigious grant. The work has yielded compelling results early. Sahlgrenska Cancer Research Center screened 206 ovarian patient derived cancer cells and confirmed the earlier findings. More interestingly, regardless of stage or sub-type, the target was present in the cytomplasm and membrane. Further expression study has shown promise in kidney, breast and GBM patient samples. 

Novel Discovery of a Potential Biomarker for Early Stage Ovarian Cancer

Screening has provided the opportunity to further research whether this specific biomarker and/or target could also be used as a diagnostic tool for detecting early stage ovarian cancer.

Road to the Clinic

Temple expects to start IND enabling studies within two years.  Temple is excited about the possibility of creating a targeted therapy for women with limited options.

Partnership Sought:

Option to license at IND or Phase 1 (build to buy)

Mode of Action TTX 334o

The expression of novel antigen and MPO in EOC cell and tissues suggests a paracrine/autocrine mechanism of survival. Interruption of this binding via targeting novel antigen with TTX334o resulted in significant anti-tumorigenic effects in vivo and in vitro. We report a unique target for ovarian cancer, and potentially other cancers, which is based on a novel survival mechanism.  

 

 

 

TTX 335o Key Takeaways

Key Data Findings

  • Potent and reproducible anti-tumor effect of TTX-335o has been demonstrated
  • Target TTX-335 does not appear to harm normal cells
  • Novel target TTX-335 has not been drugged before
  • Anti-tumor effect observed  in vitro in various cancer cell lines including colon (HTB-37), endometrial (CRL-1671), lung (CCL-257), prostate (CRL-1740), bladder (HTB-4), and hepatocelluar (HB-8065) cancers.
  • High expression in large patient samples shown in ovarian, breast, kidney, and GBM
  • Confirmed by three independent labs
  • Anti-tumor, cell killing effect demonstrated in vitro in cisplatin sensitive and resistant ovarian tumor cell lines, endometriosis and fibrosis
  • Efficacy demonstrated in vivo in mouse xenograft model of human ovarian cancer (cell line SKOV-3)
  • Mechanism of action involves induction of apoptosis in cancer cells
  • Not species or source specific
  • Strong SiRNA data confirms apoptosis of lead candidate

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