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TTX-MC138

LEAD CANDIDATE

Targeting microRNA-10b

​Our lead therapeutic candidate is focused on treating patients with metastatic cancer, an area traditionally overlooked because, from a therapeutic perspective, non-metastatic and metastatic tumor cells are often viewed as being the same.  However, metastatic tumors are fundamentally different from primary tumors.  As a result, existing cancer treatments only incrementally improve patient outcomes for later stages of the disease and, consequently, Stage III/IV cancer has an overall poor prognosis. ​
...over 90% of cancer patients who succumb to adenocarcinoma are victims of metastatic disease
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  • ​Small, non-coding strands of RNA (microRNAs) have been identified as a significant player in the pathology of cancer. 
  • Our research observed that microRNA-10b acts as a master regulator of the viability of metastatic tumor cells.
  • miR-10b is shown to be largely dispensable for normal development but critical to tumorigenesis
  • Treatment with TTX-MC138 in pre-clinical studies led to durable regression/elimination of established metastases in murine models of metastatic breast cancer.
  • miR-10b has been shown to have broad applicability across multiple cancer types.
  • Delivery strategy expected to overcome previous delivery challenges to targets outside of the liver and kidneys.
UNDERLYING MECHANISM
​The underlying mechanism of metastasis relies on two key events that we have demonstrated in our preclinical studies: ​
  1. First, a population of cells in the primary tumor over-express microRNA-10b and acquire the ability to migrate and invade surrounding tissues to form new metastases in the body (see animation to the right).
  2. Second, after these cells have upregulated the expression of microRNA-10b, they become molecularly “dependent” on this high level of expression for their survival.
Click on arrow in center of video above to begin

Use of TTX-MC138 results in the complete regression of established metastases with no recurrence and no toxicity*

  • Targets the mechanism that has been shown to regulate metastatic tumor cell survival
  • Non-invasive imaging can inform of drug bioavailability & delivery success​​
  • Broad utility across multiple metastatic cancers​
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Click on image to enlarge
* In pre-clinical studies

MECHANISM OF ACTION

How TTX-MC138 works

  • After infusion, TTX-MC138 is avidly taken up by metastatic tumor cells due to hemodynamic and metabolic targeting with our nanoparticle delivery system. Once inside metastatic tumor cells, the therapeutic Oligo and  microRNA-10b target readily bind together.
  • This binding leads to inhibition/inactivation of microRNA-10b which leads to the death of metastatic tumor cells and overall regression of the disease.
  • See the Delivery tab for more information on delivery.
Click arrow in center of animation above to begin

Importantly, TTX-MC138 is also hormone receptor independent and its mechanism of action could allow treatment of metastatic breast cancer regardless of hormone receptor type (ER+/-, PR+/-, HER2+/-, or combinations thereof). This approach could be especially beneficial for patients with triple negative breast cancer (TNBC) for whom treatment options are limited. 
CLINICAL IMPACT
Having a therapy that can address either established metastases that are clinically evident or microscopic metastases that are just initially established would be an absolute game changer for the cancer field...
Click on arrow in center of video above to begin
​Keith T. Flaherty, MD is a Professor of Medicine at Harvard Medical School, Associate Physician of Medicine, Hematology/Oncology at Massachusetts General Hospital, Director of Clinical Research, Massachusetts General Hospital Cancer Center, and Editor-in-Chief of Clinical Cancer Research. He currently serves on the Board of Directors of Clovis Oncology, Inc. (NASDAQ: CLVS) and Checkmate Pharmaceuticals, Inc. (NASDAQ: CMPI).

The FDA has not evaluated or approved TTX-MC138 and it is not currently available for patient use.
TTX is an investigational platform encompassing therapeutic candidates (including TTX-MC138) and diagnostics which remain in development. Their safety and efficacy have not yet been evaluated by the FDA or any other regulatory agency.

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  • Home
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