SPR1-0117 is a novel isoform selective inhibitor of TEAD1 / TEAD4
Preclinical data show inhibition of TEAD1 / TEAD4 drives deeper biological impact offering broader clinical potential as both monotherapy and in combination compared to TEAD1 specific inhibitors
SPR1-0117 was well-tolerated in preclinical models with no significant findings of kidney toxicity in seven-day repeat dosing
HOUSTON, TX, USA I April 17, 2023 I Sporos BioDiscovery, Inc. (a wholly owned affiliate of Sporos Bioventures, LLC. “Sporos” or the “Company”), a precision oncology company developing a diversified pipeline of small molecule therapeutic candidates, presented preclinical data for its lead candidate, SPR1-0117, a next-generation TEAD inhibitor at the American Association for Cancer Research (AACR) Annual Meeting 2023 in Orlando, FL.
SPR1-0117 targets cancers driven by mutations in the Hippo pathway, a key regulator of cell proliferation and oncogenesis not yet extensively targeted in precision oncology. The YAP1/TAZ co-activators and the TEAD family of transcription factors, which consists of four paralogs (TEAD1-4), execute the pro-cancerous effects of the Hippo pathway through transcription of pro-proliferative and anti-apoptotic genes. Hippo pathway activation has also emerged as a key mechanism of resistance to inhibitors of the MAPK pathway, making TEAD inhibitors a prime candidate for combination therapy with therapeutics targeting the MAPK pathway.
Sporos BioDiscovery’s bioinformatic analyses identified that selective inhibition of both TEAD1 and TEAD4 drives improved biological impact as compared to TEAD1 inhibitors alone, while inhibition of TEAD2 and TEAD3 were observed as undesirable due to the potential for paradoxical adverse stimulation of cell proliferation and kidney toxicity, respectively.
“We are excited to share this new data demonstrating the deep and broad biological activity of SPR1-0117 both in vitro and in vivo, not only in benchmark models of cancers driven by Hippo-pathway mutations, but in a number of cell lines beyond that of mesothelioma and NF2 mutations, including in cell lines showing only a nuclear YAP/TAZ hyperactivity. We believe this broad activity is driven by SPR1-0117’s isoform selectivity profile which inhibits both TEAD1 / TEAD4. We believe this profile may unlock the potential of SPR1-0117 as a monotherapy in a wide array of tumors with Hippo driver mutations compared to inhibitors binding primarily TEAD1,” said Stephen Rubino, Ph.D., Chief Executive Officer of Sporos Bioventures.
Dr. Rubino continued “We also see greater depth of biological response in benchmark models, with close to 80% frank regression in large, established tumors, a feat unaccomplished by other TEAD inhibitors to date. Overall, we believe SPR1-0117’s TEAD1 / TEAD4 isoform selectivity profile has been optimized as a potential best-in-class TEAD inhibitor for both monotherapy and in combination with MAPK and RTK inhibitors. We are on track to initiate IND-enabling studies for our TEAD inhibitor program this quarter and look forward to advancing our lead candidate into the clinic in 2024.”
Data reported in the poster presentation from AACR demonstrated SPR1-0117 has showed strong monotherapy activity across multiple in vitro models, including several non-mesothelioma cell lines. In addition, SPR1-0117 shows low nM potency and strong single-agent activity against TEAD-dependent benchmark in vivo models, including H226 NF2-null mesothelioma, as well as in vivo efficacy beyond mesothelioma in SCC25, an oral squamous cell carcinoma. SPR1-0117 has also demonstrated a promising ADME and safety profile in preclinical models and was shown to be well tolerated, including no significant findings of kidney toxicity, in a seven-day repeat dosing study in rats at greater than 10-times the drug exposure required for efficacy in mice.
The published poster is now available in the News & Events section of the Sporos Bioventures website.
About Sporos BioDiscovery
Sporos BioDiscovery, Inc. is a biotechnology research & development company with a diversified pipeline of several small molecule precision oncology therapeutic programs in development, including its lead candidate SPR1-0117, a next-generation TEAD inhibitor program. Sporos BioDiscovery, Inc. is a wholly-owned affiliate company of Sporos Bioventures, LLC, a private biotechnology company focused on transforming the drug development process across oncology.
SOURCE: Sporos BioDiscovery
Post Views: 645
SPR1-0117 is a novel isoform selective inhibitor of TEAD1 / TEAD4
Preclinical data show inhibition of TEAD1 / TEAD4 drives deeper biological impact offering broader clinical potential as both monotherapy and in combination compared to TEAD1 specific inhibitors
SPR1-0117 was well-tolerated in preclinical models with no significant findings of kidney toxicity in seven-day repeat dosing
HOUSTON, TX, USA I April 17, 2023 I Sporos BioDiscovery, Inc. (a wholly owned affiliate of Sporos Bioventures, LLC. “Sporos” or the “Company”), a precision oncology company developing a diversified pipeline of small molecule therapeutic candidates, presented preclinical data for its lead candidate, SPR1-0117, a next-generation TEAD inhibitor at the American Association for Cancer Research (AACR) Annual Meeting 2023 in Orlando, FL.
SPR1-0117 targets cancers driven by mutations in the Hippo pathway, a key regulator of cell proliferation and oncogenesis not yet extensively targeted in precision oncology. The YAP1/TAZ co-activators and the TEAD family of transcription factors, which consists of four paralogs (TEAD1-4), execute the pro-cancerous effects of the Hippo pathway through transcription of pro-proliferative and anti-apoptotic genes. Hippo pathway activation has also emerged as a key mechanism of resistance to inhibitors of the MAPK pathway, making TEAD inhibitors a prime candidate for combination therapy with therapeutics targeting the MAPK pathway.
Sporos BioDiscovery’s bioinformatic analyses identified that selective inhibition of both TEAD1 and TEAD4 drives improved biological impact as compared to TEAD1 inhibitors alone, while inhibition of TEAD2 and TEAD3 were observed as undesirable due to the potential for paradoxical adverse stimulation of cell proliferation and kidney toxicity, respectively.
“We are excited to share this new data demonstrating the deep and broad biological activity of SPR1-0117 both in vitro and in vivo, not only in benchmark models of cancers driven by Hippo-pathway mutations, but in a number of cell lines beyond that of mesothelioma and NF2 mutations, including in cell lines showing only a nuclear YAP/TAZ hyperactivity. We believe this broad activity is driven by SPR1-0117’s isoform selectivity profile which inhibits both TEAD1 / TEAD4. We believe this profile may unlock the potential of SPR1-0117 as a monotherapy in a wide array of tumors with Hippo driver mutations compared to inhibitors binding primarily TEAD1,” said Stephen Rubino, Ph.D., Chief Executive Officer of Sporos Bioventures.
Dr. Rubino continued “We also see greater depth of biological response in benchmark models, with close to 80% frank regression in large, established tumors, a feat unaccomplished by other TEAD inhibitors to date. Overall, we believe SPR1-0117’s TEAD1 / TEAD4 isoform selectivity profile has been optimized as a potential best-in-class TEAD inhibitor for both monotherapy and in combination with MAPK and RTK inhibitors. We are on track to initiate IND-enabling studies for our TEAD inhibitor program this quarter and look forward to advancing our lead candidate into the clinic in 2024.”
Data reported in the poster presentation from AACR demonstrated SPR1-0117 has showed strong monotherapy activity across multiple in vitro models, including several non-mesothelioma cell lines. In addition, SPR1-0117 shows low nM potency and strong single-agent activity against TEAD-dependent benchmark in vivo models, including H226 NF2-null mesothelioma, as well as in vivo efficacy beyond mesothelioma in SCC25, an oral squamous cell carcinoma. SPR1-0117 has also demonstrated a promising ADME and safety profile in preclinical models and was shown to be well tolerated, including no significant findings of kidney toxicity, in a seven-day repeat dosing study in rats at greater than 10-times the drug exposure required for efficacy in mice.
The published poster is now available in the News & Events section of the Sporos Bioventures website.
About Sporos BioDiscovery
Sporos BioDiscovery, Inc. is a biotechnology research & development company with a diversified pipeline of several small molecule precision oncology therapeutic programs in development, including its lead candidate SPR1-0117, a next-generation TEAD inhibitor program. Sporos BioDiscovery, Inc. is a wholly-owned affiliate company of Sporos Bioventures, LLC, a private biotechnology company focused on transforming the drug development process across oncology.
SOURCE: Sporos BioDiscovery
Post Views: 645
