Temple Therapeutics, a biotechnology company
pioneering a female-focused precision medicine approach, presented new in
vitro and in vivo data on TTX335o, the first drug candidate from the company’s
platform that won the Eurostar Eureka peer-reviewed grant process in
2019 for ovarian cancer, and the novel ovarian cell target, lemur tyrosine
kinase 3 (LMTK3). The new data was provided at a poster presentation at the American
Association of Cancer Research (AACR) Annual Meeting, which took place on
April 14-19, 2023 in Orlando.
“While survival rates for ovarian cancer are creeping up
to the 50% level, it is clear that the vast majority of women are diagnosed too
late,” said Sanj Singh, CEO of Temple Therapeutics. “It
has been referred to as the silent killer by some, and others have described it
as the neglected or ignored killer. Despite its lethality as the most dangerous
gynecological cancer, the field has been sparsely researched. We are changing
that. As we recognize World Ovarian Cancer Day today, we can do better. Our
sisters, aunts, spouses, friends, co-workers, mothers, and grandmothers are
affected.”
TTX335o is based on the breakthrough discovery of LMTK3
and its mechanism of action. Increased levels of LMTK3 have been shown to
affect the transcription of genes promoting DNA repair, cell viability, and
tumorigenesis which activates cell death pathways specific to cancer cells
without harming normal cells.
Preclinical data presented at AACR 2023 included:
- LMTK3 protein was
detected in 98% of ovarian cancer tissues collected from 204 patients in
various stages and major histology and localized in the nucleus of health
cells and in the cytoplasm of tumor cells.
- Risk of death among
ovarian cancer patients with more cytoplasmic than nuclear LMTK3 levels
was particularly high during the first year after diagnosis. This suggests
cytoplasmic LMTK3 expression correlates with poor survival which serves as
a potential prognostic marker for ovarian cancer patient outcomes
(p<.01).
- TTX335o specifically
targets apoptosis, a major determinant in uncontrolled cell growth in
ovarian cancer through a novel integrin (αV/β1), monomeric myeloperoxidase
(mMPO), and LMTK3 signaling pathways. Knocking down LMTK3 also induced
cell death in ovarian cancer, and more importantly, did not harm normal
cells.
- In vitro and in vivo
studies seem to validate LMTK3 as a specific target and predictor of
clinical outcomes in ovarian cancer.
Both nuclear and cytoplasmic LMTK3 expressions correlated with tumor grade and
patient survival in cancers such as breast and colorectal cancer. The clinical
significance of the LMTK3 gene was tested from 204 early-stage (stage I-II)
ovarian cancer patients of all major subtypes. Results from this study revealed
a higher cytoplasmic to nuclear localization of LMTK3 correlated with worse
overall survival (P<0.01). More importantly, engineered novel
target-specific molecules, collectively known as TTX335o, significantly induced
ovarian cancer cell death. Strikingly, TTX335o molecules are also effective in
cells resistant to chemotherapy (e.g., docetaxel or cisplatin) as in sensitive
cells.
“The discovery of this novel target almost five years ago
was surprising and exciting because we thought, what if this could be an early
detection biomarker,” said Dr. Ghassan Saed, Inventor and Lead Researcher
and Associate Professor of Gynecology Oncology at Wayne State University and
Karmanos Cancer Center in Michigan. “Dr. Helou at Sahlgrenska Cancer Center
screened the target across 204 Stage I-II ovarian cancer patient samples and
saw firsthand the correlation data of expression of the target and poor
prognosis. We knew then this may be a game changer for ovarian cancer because
it was present in all major subtypes. We saw the potential for a novel
biomarker and an associated target. We developed TTX335o to specifically target
LMTK3 pathways that kill tumors without harming normal cells, even at high
doses.”
“Treatment with TTX335o and other modalities, like siRNA,
significantly induced the killing of both chemosensitive and chemoresistant
ovarian cancer cells without affecting normal cells in vitro,“ said Anna Portela, CEO of Xenopat, a spin-off of the Catalan Institute
of Oncology (ICO), the Bellvitge Biomedical Research Institute (IDIBELL), and
the Bellvitge University Hospital (HUB). “Moreover, we observed this killing as
synergistic with both Cisplatin and Taxotere treatment in vitro. We used an
A2780 cell line-derived orthotopic xenograft mouse model of ovarian cancer to
test the efficacy of specific TTX335o in vivo. Strikingly, TTX335o 20 mg/kg IV
dose given in the same dosing schedule and duration as cisplatin showed a 35%
tumor reduction. More importantly, in vivo safety studies showed no signs of
toxicity of TTX335o, even at a very high dose of 40 mg/kg. With molecule, dose,
and schedule optimization in ongoing experiments, we could expect a higher
efficacy.”
“We have generated a substantial amount of preclinical
data demonstrating TTX335o is unlike any other targeted therapy for ovarian
cancer or approach,” said Dr. Neil Sankar, Chief Medical Officer at
Temple Therapeutics. “The addition of a companion diagnostic for early
detection, therapeutic impact, and disease progression injects much-needed hope
for ovarian cancer patients. Earlier diagnosis and intervention improve patient
outcomes. It seems that this target is agnostic across the major histological
subtypes which helps to serve the 80% of ovarian cancer patients who do not
have the BRCA genes (BReast CAncer).”
Follow the World Ovarian Cancer Coalition on Twitter @ovariancancerco and #NoWomanLeftBehind.
The AACR 2023 poster is available
upon request
at info@templerx.com.
**About
Temple Therapeutics
Temple Therapeutics is a clinical-stage, privately held
biotechnology company pioneering a female-focused precision medicine approach
for the discovery, development, and commercialization of novel therapeutics and
companion diagnostics for early detection and treatment of profibrotic
gynecological and related disorders. Temple’s mission is inspired by a belief
that medical progress must be available to all, serving the underserved women’s
health population and providing access to effective and safe treatment options
through our focus on research and new health technologies. Temple Therapeutics’
current pipeline spans endometriosis, ovarian cancer, and related disorders of
abdominal tissue fibrosis. With the goal of becoming a leading Ob/Gyn
biopharma, our vision is for a world in which gynecological health is
destigmatized, early diagnostics lead to less invasive treatments, and
healthcare is accessible and holistic—addressing physical, mental, and social
well-being. For more information, visit www.templerx.com and follow on LinkedIn.