SPR1-0117 / Sporos Bio - LARVOL DELTA

VGLL4 is the target of the 3p25 homozygous deletion and presents a novel therapeutic vulnerability for TEAD1/4 but not TEAD1 inhibitors (AACR 2024) - "We show that treatment with SPR1, Sporos's novel TEAD1/4 inhibitor, decreases tumor growth and dramatically extends survival of mice bearing VGLL4/ATG7-deleted KI2552 RCC PDX...These data emphasize the importance of targeting paralogs besides TEAD1 to broaden anti-neoplastic activity beyond mesothelioma and suggest that VGLL4-homozygous deletion confers TEAD inhibitor sensitivity even in carcinomas where it isn't the principal driver and portent exceptionally anti-neoplastic activity in neoplasms where it is. Given the wide distribution of the 3p25 homozygous deletion - our findings open a large new potential responder population to TEAD inhibitors and warrant inclusion of VGLL4 in NSG diagnostic sequencing panels."

Clear Cell Renal Cell Carcinoma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • ATG7 • TEAD1 • VGLL4 • YAP1

TEAD1/4 inhibitors exhibit deeper biological impact and broader activity compared to TEAD1-only inhibitors in both monotherapy and combination without additional kidney toxicity (AACR 2024) - "However, the TEAD1-preferential inhibitor IK930 did not yield any objective responses but also showed a more favorable safety profile especially with respect to proteinuria. We show that 1) SPR1 displays broader and deeper cell-based activity and extends the utility of TEAD inhibitors outside of mesothelioma and NF2 mutants 2) SPR1 shows stronger activity than TEAD1-only inhibitors in combination with MAPK and EGFR inhibitors in vitro and in vivo 3) SPR1 does not cause proteinuria in mice; dogs or rats even above therapeutic doses 4) SPR1 does not show the context-specific stimulation of tumor growth in Lung PDX previously observed with VT3989 and other inhibitors that include TEAD2 in their profile. Taken together - the data suggests SPR1 is positioned to become a best-in-class TEAD palmitic acid site inhibitor with broad utility in both monotherapy and combination setting."

Monotherapy • Mesothelioma • Oncology • Solid Tumor • NF2 • TEAD1 • TEAD2 • TEAD3

Sporos BioDiscovery to Present Preclinical Findings on SPR1, a Next-Generation TEAD Inhibitor, at the American Association for Cancer Research (AACR) Annual Meeting 2024 (Businesswire) - "Sporos BioDiscovery...announced that it will present two posters highlighting preclinical data from the company’s novel TEAD1 / TEAD4 isoform selective inhibitor, SPR1, at the American Association for Cancer Research (AACR) Annual Meeting 2024..."

Preclinical • Oncology

Sporos BioDiscovery Presents Preclinical Data on Next-Generation TEAD Inhibitor, SPR1-0117, at the American Association for Cancer Research (AACR) Annual Meeting 2023 (Businesswire) - "Sporos BioDiscovery, Inc...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....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."

Preclinical • Mesothelioma • Oncology • Solid Tumor • Squamous Cell Carcinoma

A next generation TEAD inhibitor with refined isoform specificity for superior safety & efficacy (AACR 2023) - "(iv) favorable ADME profile in rodents, dogs and NHPs, as well as a favorable safety profile. In sum, SPR1 presents monotherapy opportunities in ultra-responder populations based on internal bioinformatic insights, while broader potential exists as an adjuvant for precision oncology targeted therapies, particularly within the MAPK pathway and its upstream activators."

Clinical • Lung Cancer • Mesothelioma • Oncology • Solid Tumor • TEAD1 • WWTR1 • YAP1

Sporos BioDiscovery to Present Preclinical Findings on SPR1, a Next-Generation TEAD Inhibitor, at the American Association for Cancer Research (AACR) Annual Meeting 2023 (Businesswire) - "Sporos BioDiscovery, Inc...announced that it will present a poster highlighting preclinical data from the company’s novel, isoform selective TEAD inhibitor, SPR1, at the American Association for Cancer Research (AACR) Annual Meeting 2023 taking place April 14-19, 2023, in Orlando, FL."

Preclinical • Oncology • Solid Tumor

A family of novel TEAD palmitoylation site inhibitors with exceptional pre-clinical anti-neoplastic activity as a monotherapy and in combination with MAPK inhibitors (AACR-NCI-EORTC 2022) - "The lead TEAD inhibitor, SPR1-TE-0294, caused rapid and dramatic tumor regression even in very large (>800 mm3) xenografted tumors... TEAD inhibitors show exceptional anti-tumor effects in pre-clinical models in vivo, despite somewhat modest effects in vitro. We speculate that cell culture conditions (attachment, serum) minimize dependence on the Hippo pathway, and that TEAD inhibitors may have much broader utility than cell line-screening studies have suggested."

Combination therapy • Monotherapy • Preclinical • Oncology • BRAF • EGFR • KRAS

Sporos BioDiscovery Presents Preclinical Data on Differentiated TEAD Inhibitor Program, SPR1, at the 34th EORTC-NCI-AACR Symposium (Businesswire) - "Sporos BioDiscovery...announced its poster presentation highlighting preclinical data on the Company’s lead program, SPR1, a differentiated, novel TEAD inhibitor at 34th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics....'These preclinical data sets demonstrate compound safety and superior in vivo single-agent activity in large-volume tumor models and in combination with KRAS, MEK, and RTK inhibitors'....'Our data supports our initiative to move SPR1 into clinical development with a goal of filing an IND before the end of 2023'."

IND • Preclinical