PTGR1

DALLAS--(BUSINESS WIRE) December 03, 2024 -- Lantern Pharma Inc. (NASDAQ: LTRN), an artificial intelligence (AI) company dedicated to developing cancer therapies and transforming the cost, pace, and timeline of oncology drug discovery and development, today announced that the FDA has granted Fast Track Designation for investigational drug candidate, LP-184, for treatment of Triple Negative Breast Cancer (TNBC). This marks the second Fast Track Designation received for LP-184 in 2024, following its designation for Glioblastoma in October. LP-184 is currently in a Phase 1A clinical trial designed to evaluate the safety and tolerability of this synthetically lethal investigational drug candidate in a broad range of solid tumors, including TNBC. LP-184 was optimized and advanced in part with Lantern's AI platform, RADR®, which helped validate mechanisms that could be exploited in the clinical setting to eradicate challenging cancers and uncover insights in targeted patient populations. "Receiving a second FDA Fast Track Designation for LP-184 reinforces the significant potential of this drug candidate to address critical unmet needs in aggressive cancers, especially those like TNBC where patients have limited therapeutics options," stated Panna Sharma, President and CEO of Lantern Pharma. "Recent data presented at the Immuno-Oncology Summit demonstrated LP-184's ability to sensitize TNBC tumors that are non-responsive to checkpoint inhibitors, potentially expanding treatment options for patients with limited therapeutic choices." About TNBC and the Need for Novel Therapies TNBC represents approximately 20% of all breast cancers, affecting nearly 29,000 patients annually in the US. The prognosis for TNBC patients is considerably worse than hormone receptor-positive breast cancers, with over 50% of patients relapsing in the first 3-5 years and metastatic TNBC patients having a median overall survival of less than one year. Currently available treatment options are limited, particularly for patients who develop resistance to existing therapies. Compelling Preclinical Data Demonstrates LP-184's Potential in TNBC The graph above demonstrates LP-184's remarkable anti-tumor activity across a panel of 10 TNBC patient-derived xenograft (PDX) models. Notably, LP-184 showed consistent efficacy in both PARPi (PARP inhibitor) resistant and PARPi sensitive tumors, with treatment resulting in complete tumor regression (107-141% tumor growth inhibition) across all models tested. This data is particularly significant as it suggests LP-184's potential as a novel therapeutic option for TNBC patients, including those who have developed resistance to existing PARP inhibitor treatments - a growing clinical challenge in TNBC therapy. This TNBC data was initially presented at the San Antonio Breast Cancer Symposium in 2022. LP-184's unique mechanism of action is driven by the enzymatic activation of the drug by Prostaglandin Reductase 1 (PTGR1), which converts LP-184 into its highly potent cytotoxic form specifically within cancer cells. RADR® platform analysis and subsequent in-vivo validation studies have shown that PTGR1 is frequently elevated in TNBC tumors compared to normal tissue, making these cancers particularly susceptible to LP-184 treatment. This biomarker-driven approach allows for the potential identification of patients most likely to respond to LP-184 therapy, aligning with current and emerging precision medicine approaches in TNBC treatment. About LP-184 LP-184 is a small molecule drug candidate and next-generation acylfulvene that preferentially damages DNA in cancer cells that overexpress specific biomarkers or harbor mutations in DNA damage repair pathways. LP-184 was developed using Lantern's proprietary RADR® AI platform to identify patient populations and cancer subtypes that have the potential to respond to treatment. The compound is being evaluated in multiple solid tumors where it has shown nanomolar potency and activity in drug-resistant cancers. LP-184 has received Orphan Drug Designations from the FDA for the treatment of pancreatic cancer, glioblastoma (GBM), and ATRT, and has also been granted a Rare Pediatric Disease Designation for ATRT. About Lantern Pharma Lantern Pharma (NASDAQ: LTRN) is an AI company transforming the cost, pace, and timeline of oncology drug discovery and development. Our proprietary AI and machine learning (ML) platform, RADR®, leverages over 100 billion oncology-focused data points and a library of 200+ advanced ML algorithms to help solve billion-dollar, real-world problems in oncology drug development. By harnessing the power of AI and with input from world-class scientific advisors and collaborators, we have accelerated the development of our growing pipeline of therapies that span multiple cancer indications, including both solid tumors and blood cancers and an antibody-drug conjugate (ADC) program. Our lead development programs include a Phase 2 clinical program and multiple Phase 1 clinical trials. Our AI-driven pipeline of innovative product candidates is estimated to have a combined annual market potential of over $15 billion USD and have the potential to provide life-changing therapies to hundreds of thousands of cancer patients across the world. FORWARD LOOKING STATEMENT: This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These forward-looking statements include, among other things, statements relating to: future events or our future financial performance; the potential advantages of our RADR ® platform in identifying drug candidates and patient populations that are likely to respond to a drug candidate; our strategic plans to advance the development of our drug candidates and antibody drug conjugate (ADC) development program; estimates regarding the development timing for our drug candidates and ADC development program; expectations and estimates regarding clinical trial timing and patient enrollment; our research and development efforts of our internal drug discovery programs and the utilization of our RADR ® platform to streamline the drug development process; our intention to leverage artificial intelligence, machine learning and genomic data to streamline and transform the pace, risk and cost of oncology drug discovery and development and to identify patient populations that would likely respond to a drug candidate; estimates regarding patient populations, potential markets and potential market sizes; sales estimates for our drug candidates and our plans to discover and develop drug candidates and to maximize their commercial potential by advancing such drug candidates ourselves or in collaboration with others. Any statements that are not statements of historical fact (including, without limitation, statements that use words such as "anticipate," "believe," "contemplate," "could," "estimate," "expect," "intend," "seek," "may," "might," "plan," "potential," "predict," "project," "target," “model,” "objective," "aim," "upcoming," "should," "will," "would," or the negative of these words or other similar expressions) should be considered forward-looking statements. There are a number of important factors that could cause our actual results to differ materially from those indicated by the forward-looking statements, such as (i) the risk that our research and the research of our collaborators may not be successful, (ii) the risk that observations in preclinical studies and early or preliminary observations in clinical studies do not ensure that later observations, studies and development will be consistent or successful, (iii) the risk that we may not be able to secure sufficient future funding when needed and as required to advance and support our existing and planned clinical trials and operations, (iv) the risk that we may not be successful in licensing potential candidates or in completing potential partnerships and collaborations, (v) the risk that none of our product candidates has received FDA marketing approval, and we may not be able to successfully initiate, conduct, or conclude clinical testing for or obtain marketing approval for our product candidates, (vi) the risk that no drug product based on our proprietary RADR ® AI platform has received FDA marketing approval or otherwise been incorporated into a commercial product, and (vii) those other factors set forth in the Risk Factors section in our Annual Report on Form 10-K for the year ended December 31, 2023, filed with the Securities and Exchange Commission on March 18, 2024. You may access our Annual Report on Form 10-K for the year ended December 31, 2023 under the investor SEC filings tab of our website at www.lanternpharma.com or on the SEC's website at www.sec.gov. Given these risks and uncertainties, we can give no assurances that our forward-looking statements will prove to be accurate, or that any other results or events projected or contemplated by our forward-looking statements will in fact occur, and we caution investors not to place undue reliance on these statements. All forward-looking statements in this press release represent our judgment as of the date hereof, and, except as otherwise required by law, we disclaim any obligation to update any forward-looking statements to conform the statement to actual results or changes in our expectations. Source: Lantern Pharma Inc. Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

DALLAS--(BUSINESS WIRE)-- Lantern Pharma (NASDAQ: LTRN), a clinical-stage biopharmaceutical company leveraging artificial intelligence (AI) and machine learning to transform the cost, pace, and timeline of oncology drug discovery and development, today announced a significant advancement towards the development of a diagnostic for its drug candidate LP-184. The diagnostic is currently based on qRT-PCR (quantitative real-time polymerase chain reaction) technology and is focused on quantifying the amount of PTGR1 RNA in patient tumor samples to assess the potential for sensitivity to Lantern’s drug candidate LP-184. The company plans to further develop and validate the assay for its use as a potential tool for patient selection in later stage clinical trials across a broad range of solid tumors that have shown sensitivity to LP-184. This press release features multimedia. View the full release here: Figure 1: Correlation of PTGR1 expression and cytotoxicity/potency (IC50, µM) of LP-184 (Graphic: Business Wire) Lantern has successfully confirmed PTGR1 as a key biomarker that it intends to use to optimize patient selection based on potential tumor sensitivity to the drug candidate LP-184. LP-184 is a precision oncology drug candidate with the potential to address multiple solid tumors. This confirmation marks a crucial step towards the development of a companion diagnostic and potential stratification tool to assist with targeted patient selection. Lantern plans on further validations and development of the assay using qRT-PCR and partnering with central labs and cancer centers for eventual use in patient selection and stratification. In a key publication on the utility and value of biomarkers in oncology trials among some of the most common cancers, titled Does biomarker use in oncology improve clinical trial failure risk? A large‐scale analysis by Parker, et al., 2021 in Cancer Medicine found success of clinical trials to be significantly correlated to the incorporation of biomarkers. In particular, the Parker, et al. publication stated that: “…Our overall analysis of these four cancers, independent of indication, revealed a fivefold benefit of hazard ratios from the Markov models, suggesting a substantial benefit from biomarker use. The hazard ratio analysis of the Markov biomarker models examined how likely clinical trial success was associated with biomarker use versus no biomarker use. Hazard ratios indicated that for biomarker‐based drugs clinical trial success was largest for breast cancer (12‐fold) followed by melanoma (eightfold) and lung cancer (sevenfold) …Our data provide the most extensive look at biomarker use to date in oncology, with an advanced statistical method. Our findings indicate that biomarkers provide a statistically significant benefit, despite the fact our study includes biomarkers not yet FDA approved.” By incorporating the PTGR1 biomarker into LP-184's development strategy, Lantern Pharma is aligning with best practices in precision medicine and aiming to increase the likelihood of successful clinical outcomes in future clinical trials. PTGR1 levels have been measured to be higher in certain cancer cells than in normal cells, and Lantern is leveraging this biological activity to target the cancer indications believed most likely to respond to drug candidate LP-184. In the October 2023 paper in Molecular Cancer Therapeutics, Lantern along with collaborators from Fox Chase Cancer Center published clear evidence that higher potency of LP-184 (measured in IC50 values) was directly correlated with higher expressions of PTGR1 and that cancer cell lines that did not have PTGR1 expression remained stable in the presence of LP-184 (see figure 1). "This milestone represents a significant leap forward in our precision oncology approach and in ensuring that we enrich our future LP-184 clinical trials with the patients we believe will be most likely to benefit," said Panna Sharma, CEO of Lantern Pharma. "By working to develop a companion diagnostic for LP-184, we're not just advancing a drug candidate; we're paving the way for more personalized and effective cancer treatments for patients that have the highest likelihood of benefitting from the therapy. The planned use of biomarkers like PTGR1 in our clinical trials exemplifies our commitment to data-driven, patient-centric drug development." These steps toward development of this companion diagnostic align with Lantern Pharma's commitment to leveraging cutting-edge technology in drug development. By combining AI-driven insights with advanced diagnostic tools, the company aims to accelerate the drug development process and improve patient outcomes. Lantern Pharma plans to implement this assay in upcoming clinical trials for LP-184, potentially streamlining the development process and increasing the likelihood of successful outcomes. LP-184— a novel therapeutic in clinical development for the potential treatment of malignant gliomas, pancreatic cancer, and atypical teratoid rhabdoid tumors (ATRT)— has also been granted an Orphan Drug Designation by the FDA, along with a Rare Pediatric Disease Designation. About Lantern Pharma: Lantern Pharma (NASDAQ: LTRN) is an AI company transforming the cost, pace, and timeline of oncology drug discovery and development. Our proprietary AI and machine learning (ML) platform, RADR®, leverages over 60 billion oncology-focused data points and a library of 200+ advanced ML algorithms to help solve billion-dollar, real-world problems in oncology drug development. By harnessing the power of AI and with input from world-class scientific advisors and collaborators, we have accelerated the development of our growing pipeline of therapies that span multiple cancer indications, including both solid tumors and blood cancers and an antibody-drug conjugate (ADC) program. On average, our newly developed drug programs have been advanced from initial AI insights to first-in-human clinical trials in 2-3 years and at approximately $1.0 - 2.5 million per program. Our lead development programs include a Phase 2 clinical program and multiple Phase 1 clinical trials. We have also established a wholly-owned subsidiary, Starlight Therapeutics, to focus exclusively on the clinical execution of our promising therapies for CNS and brain cancers, many of which have no effective treatment options. Our AI-driven pipeline of innovative product candidates is estimated to have a combined annual market potential of over $15 billion USD and have the potential to provide life-changing therapies to hundreds of thousands of cancer patients across the world. Please find more information at: Website: LinkedIn: X: @lanternpharma Forward-looking Statements: This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These forward-looking statements include, among other things, statements relating to: future events or our future financial performance; the potential advantages of our RADR® platform in identifying drug candidates and patient populations that are likely to respond to a drug candidate; our strategic plans to advance the development of our drug candidates and antibody drug conjugate (ADC) development program; estimates regarding the development timing for our drug candidates and ADC development program; expectations and estimates regarding clinical trial timing and patient enrollment; our research and development efforts of our internal drug discovery programs and the utilization of our RADR® platform to streamline the drug development process; our intention to leverage artificial intelligence, machine learning and genomic data to streamline and transform the pace, risk and cost of oncology drug discovery and development and to identify patient populations that would likely respond to a drug candidate; estimates regarding patient populations, potential markets and potential market sizes; sales estimates for our drug candidates and our plans to discover and develop drug candidates and to maximize their commercial potential by advancing such drug candidates ourselves or in collaboration with others. Any statements that are not statements of historical fact (including, without limitation, statements that use words such as "anticipate," "believe," "contemplate," "could," "estimate," "expect," "intend," "seek," "may," "might," "plan," "potential," "predict," "project," "target," “model,” "objective," "aim," "upcoming," "should," "will," "would," or the negative of these words or other similar expressions) should be considered forward-looking statements. There are a number of important factors that could cause our actual results to differ materially from those indicated by the forward-looking statements, such as (i) the risk that our research and the research of our collaborators may not be successful, (ii) the risk that promising observations in preclinical studies do not ensure that later studies and development will be successful, (iii) the risk that we may not be successful in licensing potential candidates or in completing potential partnerships and collaborations, (iv) the risk that none of our product candidates has received FDA marketing approval, and we may not be able to successfully initiate, conduct, or conclude clinical testing for or obtain marketing approval for our product candidates, (v) the risk that no drug product based on our proprietary RADR® AI platform has received FDA marketing approval or otherwise been incorporated into a commercial product, and (vi) those other factors set forth in the Risk Factors section in our Annual Report on Form 10-K for the year ended December 31, 2023, filed with the Securities and Exchange Commission on March 18, 2024. You may access our Annual Report on Form 10-K for the year ended December 31, 2023 under the investor SEC filings tab of our website at or on the SEC's website at . Given these risks and uncertainties, we can give no assurances that our forward-looking statements will prove to be accurate, or that any other results or events projected or contemplated by our forward-looking statements will in fact occur, and we caution investors not to place undue reliance on these statements. All forward-looking statements in this press release represent our judgment as of the date hereof, and, except as otherwise required by law, we disclaim any obligation to update any forward-looking statements to conform the statement to actual results or changes in our expectations. View source version on businesswire.com: Contacts Investor Relations mailto: ir@lanternpharma.com ph: (972) 277-1136 Source: Lantern Pharma Smart Multimedia Gallery Photo Figure 1: Correlation of PTGR1 expression and cytotoxicity/potency (IC50, µM) of LP-184 (Graphic: Business Wire) Logo View this news release and multimedia online at:

前列腺癌（PCa）是美国最常见的男性恶性肿瘤，也是癌症死亡的第二大原因。到目前为止，由于疾病的异质性，PCa治疗仍然面临巨大挑战。尽管接受雄激素剥夺治疗（ADT）、手术、放疗和化疗的前列腺癌患者往往复发风险较低，生存率较高，但代谢综合征的表现，如肥胖、胰岛素抵抗和糖耐量受损，往往发生在治疗后，最终导致耐药性和远端转移。根据各种临床试验，二甲双胍治疗PCa的疗效似乎不确定。二甲双胍治疗失败可能归因于高频率的转录失调，从而导致耐药性。然而，其根本机制仍不清楚。2023年8月16日，华南理工大学钟惟德、韩兆冬及加州大学河滨分校贾震宇共同通讯在Signal Transduction and Targeted Therapy 在线发表了题为“Metformin escape in prostate cancer by activating the PTGR1 transcriptional program through a novel super-enhancer”的研究论文，该研究揭示通过一种新型超增强子激活PTGR1转录程序，以致二甲双胍在前列腺癌中逃逸。该研究发现PCa细胞对二甲双胍的耐药性可能与细胞周期再激活有关。超级增强子（SEs）是关键的调节元件，已被证明与各种癌症的耐药性有关。研究者对二甲双胍耐药性（MetR）前列腺癌细胞中SEs的分析揭示了与前列腺素还原酶1（PTGR1）表达的相关性，通过单细胞转录组测序，发现前列腺素还原酶1在一组二甲双胍耐药性细胞中显著增加。功能实验表明，PTGR1过表达通过促进从G0/G1期到S期和G2/M期的进展来加速细胞周期进展，从而降低对二甲双胍的敏感性。此外，研究者确定了显著增加PTGR1表达的关键转录因子，如SRF和RUNX3，为解决前列腺癌中的二甲双胍耐药性提供了潜在的新靶点。总之，该研究为二甲双胍耐药性的细胞机制和SE-TFs-PTGR1轴的调节提供了新的线索，为提高二甲双胍对前列腺癌的治疗效果提供了潜在的途径。为了维持PCa细胞充足的能量供应，在前列腺上皮内瘤变向转移的过程中，细胞代谢继续发生改变。例如，健康的前列腺细胞利用柠檬酸盐合成前列腺液，从而在很大程度上抑制三羧酸（TCA）循环。相反，侵袭性PCa细胞的能量产生主要通过TCA循环和氧化磷酸化（OXPHOS）完成。然而，据报道，在转移性PCa细胞中，OXPHOS水平降低，而糖酵解活性补偿性增加。总之，先前的研究表明，PCa可能在不同阶段依赖不同的代谢途径来产生能量，为精准治疗提供了潜在的靶点。二甲双胍是一种一线口服降血糖药物，其来源于草药Galega officinalis的提取物。越来越多的研究表明，二甲双胍可能是PCa的潜在候选辅助治疗剂，因为它具有多种抗癌作用、令人满意的人体耐受性和低成本。二甲双胍不仅具有良好的降血糖作用，而且通过诱导G0/G1阻滞和降低OXPHOS水平来调节肿瘤细胞代谢，从而抑制癌症的生长。尽管积累的临床数据已经证明二甲双胍治疗与PCa患者的良好预后之间存在关联，但据报道，某些患者对二甲双胍没有反应。这与之前的一项研究一致，该研究初步证明，由于肿瘤异质性，二甲双胍治疗对各种癌症产生耐药性。因此，研究者假设PCa患者的一个亚群可能在一段时间的治疗后出现二甲双胍耐药性，并旨在深入了解其潜在机制。文章模式图（图源自Signal Transduction and Targeted Therapy ）该研究使用PCa细胞系产生了两种体外MetR细胞模型，即DU145和22RV1。有趣的是，停药30天后，这些MetR细胞恢复了对二甲双胍的敏感性，这表明二甲双胍耐药性可能是一种暂时的非突变细胞表型。通过实验和RNA-seq分析，该研究发现PCa细胞中的二甲双胍耐药性可能与细胞周期和代谢重编程的变化有关。此外，单细胞转录组测序结果显示，关键基因前列腺素还原酶1（PTGR1）在DU145-MetR细胞群中上调，这与二甲双胍耐药性有关。H3K27ac ChIP-Seq数据和其他实验表明，位于PTGR1上游并由关键转录因子SRF和RUNX3结合的新SE可能与PTGR1的上调有关。研究者证明PTGR1通过干扰细胞周期阻滞对二甲双胍治疗产生拮抗作用，这可能与E2F3的作用有关。该研究首次表明：（1）当与SRF和RUNX3结合时，这种SE增加了DU145 MetR细胞中PTGR1的表达；（2）PTGR1表达的增加通过促进从G0/G1向S和G2/M期的进展来加速细胞周期的进展，降低了二甲双胍对PCa的抑制作用。文章来源“iNture”责编|文竞择校对|文竞择End往期精选围观历史性突破！不需卵子和精子就可以合成人类胚胎热文富豪用儿子血浆“回春”科学吗？Science：血液牛磺酸缺乏驱动衰老热文世界首例！35岁的她，通过机器人操刀移植的子宫，成功诞下宝宝热文为了避免心脏骤停，53岁的他成为“第一个”植入开创性除颤器的心脏病患者热文首次披露！175家生物制药公司的薪资数据：薪资中位数达20万美元点击“阅读原文”，了解更多~