TEAD2

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--(BUSINESS WIRE)-- 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 pro inhibits both TEAD1 / TEAD4. We believe this pro 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 pro 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 pro 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. Forward-Looking Statements This press release contains forward-looking statements, including, without limitation, statements regarding plans, strategies, timelines and expectations for Sporos Bioventures LLC (“Sporos”) and its affiliates’ current or future approved discovery-stage and development product candidates, including the potential benefits of any of Sporos and its affiliates’ current or future product candidates in treating patients; and their strategy, goals and anticipated financial performance, milestones, business plans and focus. The words “aim,” “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this presentation are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks and uncertainties related to ongoing and planned research and development activities, including initiating, conducting or completing discovery-stage or preclinical studies and clinical trials and the timing and results of such preclinical studies or clinical trials; the delay of any current or planned development and clinical activities, or clinical trials or the development of Sporos and its affiliates’ current or future product candidates; preclinical and clinical supply of current or future product candidates; Sporos and its affiliates’ advancement of multiple early-stage efforts; Sporos and its affiliates’ ability to successfully demonstrate the safety and efficacy of its product candidates and gain approval of its product candidates on a timely basis, if at all; the preclinical and clinical results for Sporos and its affiliates’ product candidates, which may not support further development of such product candidates; actions of regulatory agencies, which may affect the initiation, timing and progress of current or future development and clinical activities and trials; Sporos and its affiliates’ ability to obtain, maintain and enforce patent and other intellectual property protection for current or future product candidates; Sporos and its affiliates’ ability to obtain and maintain sufficient cash resources to fund current or future operating expenses and capital expenditure requirements; and the impact of the COVID-19 pandemic on Sporos and its affiliates’ business, operations, strategy, goals and anticipated milestones. Any forward-looking statements contained in this press release represent Sporos and its affiliates’ views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Except as required by law, Sporos and its affiliates explicitly disclaim any obligation to update any forward-looking statements.

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

SPR1 Demonstrates Single Agent Anti-Tumor Activity in vivo, Achieving Regression in Established, Large Volume Tumors SPR1 Synergizes with MAPK Inhibitors and Upstream Activators of the MAPK Pathway HOUSTON--(BUSINESS WIRE)-- Sporos BioDiscovery, Inc. (a wholly owned affiliate of Sporos Bioventures, “Sporos” or the “Company”), a precision oncology company developing a diversified pipeline of small molecule therapeutic programs targeting cancer vulnerabilities in the tumor and tumor microenvironment, today 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, taking place October 26-28, 2022, in Barcelona, Spain. “We were excited to present preclinical data from SPR1, a next-generation, finely tuned TEAD inhibitor program, with a unique TEAD isoform selectivity that we believe sets it apart from other TEAD inhibitors and offers a potential best-in-class profile. 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,” said Dr. Stephen Rubino, Chief Executive Officer of Sporos. “Our data supports our initiative to move SPR1 into clinical development with a goal of filing an IND before the end of 2023.” The Hippo pathway (effected by the YAP/TAZ-TEAD transcriptional complex) is a major oncogenic pathway and hyperactivation of YAP/TAZ-TEAD transcription has been demonstrated as a key mechanism of resistance to MAPK pathway inhibition, as well as inhibition of its upstream inputs, such as EGFR and other receptor tyrosine kinases. The poster presents the first disclosure of SPR1, Sporos TEAD inhibitor program. Highlights of the poster, titled “A Family of Novel TEAD Palmitoylation Site Inhibitors with Exceptional Pre-clinical Anti-neoplastic Activity as a Monotherapy and in Combination with MAPK Inhibitors,” include: The synthesis of a series of small molecule inhibitors of TEAD transcription factors with nM activity in a broad range of cancer cell lines, coupled with favorable pharmacokinetic and safety pro Fine-tuning of TEAD isoform specificity yielded exceptional TEAD inhibitors with low toxicity (MTD >300 mg/kg, >20X efficacious dose) coupled with high anti-tumor efficacy. Sporos' TEAD inhibitors yield rapid regression even in very large pre-clinical tumors, a first in the TEAD-inhibitor space. Sporos' TEAD inhibitors show strong synergy with precision oncology drugs targeting the MAPK pathway and its upstream inputs, including Sotorasib, Trametinib, and Osimertinib. Differentiated activity pro SPR1 TEAD inhibitors may derive from favorable TEAD isoform inhibitory specificity. 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, a novel TEAD inhibitor program. Sporos BioDiscovery is a wholly-owned affiliate company of Sporos Bioventures, LLC, a private biotechnology company focused on transforming the drug development process across oncology. Forward-Looking Statements This press release contains forward-looking statements, including, without limitation, statements regarding plans, strategies, timelines and expectations for Sporos Bioventures LLC (“Sporos”) and its affiliates’ current or future approved discovery-stage and development product candidates, including the potential benefits of any of Sporos and its affiliates’ current or future product candidates in treating patients; and their strategy, goals and anticipated financial performance, milestones, business plans and focus. The words “aim,” “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this presentation are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks and uncertainties related to ongoing and planned research and development activities, including initiating, conducting or completing discovery-stage or preclinical studies and clinical trials and the timing and results of such preclinical studies or clinical trials; the delay of any current or planned development and clinical activities, or clinical trials or the development of Sporos and its affiliates’ current or future product candidates; preclinical and clinical supply of current or future product candidates; Sporos and its affiliates’ advancement of multiple early-stage efforts; Sporos and its affiliates’ ability to successfully demonstrate the safety and efficacy of its product candidates and gain approval of its product candidates on a timely basis, if at all; the preclinical and clinical results for Sporos and its affiliates’ product candidates, which may not support further development of such product candidates; actions of regulatory agencies, which may affect the initiation, timing and progress of current or future development and clinical activities and trials; Sporos and its affiliates’ ability to obtain, maintain and enforce patent and other intellectual property protection for current or future product candidates; Sporos and its affiliates’ ability to obtain and maintain sufficient cash resources to fund current or future operating expenses and capital expenditure requirements; and the impact of the COVID-19 pandemic on Sporos and its affiliates’ business, operations, strategy, goals and anticipated milestones. Any forward-looking statements contained in this press release represent Sporos and its affiliates’ views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Except as required by law, Sporos and its affiliates explicitly disclaim any obligation to update any forward-looking statements.