IGFBP3

AUSTIN, Texas, Nov. 21, 2024 (GLOBE NEWSWIRE) -- Lumos Pharma, Inc. (NASDAQ:LUMO), a clinical-stage biopharmaceutical company focused on therapeutics for rare diseases, announced that new analyses of data from its Phase 2 OraGrowtH210 and OraGrowtH212 clinical trials were presented orally at the 62nd Annual European Society for Paediatric Endocrinology Meeting, or ESPE 2024, held November 16-18, 2024 in Liverpool, UK. “The new analyses and updated data from our Phase 2 OraGrowtH210 and OraGrowtH212 Trials presented at ESPE this week demonstrate sustained growth on LUM-201 in moderate Pediatric Growth Hormone Deficiency (PGHD) to 24 months, as well as the correlation of LUM-201’s pulsatile mechanism of action (MOA) to growth,” said John C. McKew, PhD, President and Chief Scientific Officer of Lumos Pharma. “We are encouraged by these data and look forward to advancing oral LUM-201 in a Phase 3 clinical trial in moderate PGHD next year.” In the oral presentation of Abstract FC7.6 on Sunday, November 17th, entitled, Growth, IGF-1 and IGFBP-3 Responses to Oral LUM-201 in OraGrowtH210 and OraGrowtH212 Trials in Pediatric Growth Hormone Deficiency (PGHD) Over 12 to 24 Months on Treatment (Elżbieta Petriczko, MD, PhD, et al) [link], the investigator reviewed updated combined data from the Phase 2 OraGrowtH210 and OraGrowtH212 Trials out to 24 months following treatment with LUM-201. Results showed that at six months on LUM-201, a significant increase over baseline in Annualized Height Velocity (AHV) was observed for the combined 1.6 and 3.2 mg/kg/day doses. At baseline, AHV was 4.6 cm/yr for 37 subjects for which baseline data were available vs 7.8 cm/yr at 6 months on LUM-201 for 66 subjects.Results also showed that growth rates on oral LUM-201 (combined 1.6 and 3.2 mg/kg dose cohorts) were sustained out to 24 months with AHVs of 7.3 (N=65), 7.5 (N=36), and 7.3 (N=20) cm/yr at 12, 18, and 24 months, respectively [graphic below]. Combined results also demonstrated significant increases in IGF-1 and IGFBP-3 levels from baseline out to 24 months, with IGF-1 increasing from 13.1 (baseline) to 25.5 (12 months) to 29.2 (24 months) nmol/L and IGFBP-3 increasing from 133.5 (baseline) to 179.6 (12 months) to 186.2 (24 months) nmol/L.Conclusions: LUM-201 shows a significant increase in AHV at 6 months, and the effect continues with a minimal decrease in AHV through 24 months. Compared to historical rhGH (KIGS)1, LUM-201 has a smaller drop in AHV from 12 months to 24 months. LUM-201 significantly increases IGF-1 and IGFBP-3 levels at 12 months which continues to 24 months. A favorable investigational safety profile has been observed to date. In the late-breaking oral presentation of Abstract FC15.2 on Monday, November 18th, entitled, Amount and Pattern of Pulsatile GH Secretion Induced by the Oral Growth Hormone Secretagogue LUM-201 Is Related to Growth and IGF-1 Responses in Moderate Pediatric Growth Hormone Deficiency (PGHD) (Peter E. Clayton, MD, et al) [link], the investigator reviewed data from OraGrowtH212 demonstrating the relationship between pulsatile GH profiles and both the growth and IGF-1 responses to LUM-201 treatment. Data from 22 prepubertal children with moderate PGHD from the OraGrowtH212 Trial were evaluated with subjects grouped into tertiles based on 6-month annualized height velocity (AHV).Pulsatile growth hormone (GH) pulse assessments at baseline and at 6 months (M6) were characterized using 1) Approximate Entropy (ApEn, scale 0-1) examining degree of orderliness over the whole profile and 2) Functional Principal Component Analysis (FPCA) identifying where within the 12-hour profile, divided into 4-hour periods, the dominant variation occurred.Results of 6-month treatment with LUM-201: Pulsatile GH secretion, ApEn, IGF-1 SDS and IGFBP-3 SDS increased from baseline to M6.Greater M6 AHV was associated with an earlier periodicity of augmented pulsatile GH secretion [graphic below]. Conclusion: Both amount and pattern of GH secretion are important for growth and IGF-1 responses to LUM-201. 1 Ranke et al., 2010 – Pfizer KIGS database rhGH treated cohort of moderate prepubertal GHD children. About Lumos Pharma Lumos Pharma, Inc. is a clinical stage biopharmaceutical company focused on the development and commercialization of therapeutics for rare diseases. The Company was founded and is led by a management team with longstanding experience in rare disease drug development. Lumos Pharma’s lead therapeutic candidate, LUM-201, is a novel, oral growth hormone (GH) secretagogue, seeking to transform the ~$4.7B global GH market from injectable to oral therapy. LUM-201 is currently being evaluated in multiple Phase 2 clinical studies in Pediatric Growth Hormone Deficiency (PGHD) and has received Orphan Drug Designation in both the US and EU. For more information, please visit https://lumos-pharma.com/. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements of Lumos Pharma, Inc. that involve substantial risks and uncertainties. All such statements contained in this press release are forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. A law that, in part, gives us the opportunity to share our outlook for the future without fear of litigation if it turns out our predictions were not correct. We are passionate about our business - including LUM-201 and the potential it may have to help patients in the clinic. This passion feeds our optimism that our efforts will be successful and bring about meaningful change for patients. Please keep in mind that actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements that we make. We have attempted to identify forward-looking statements by using words such as “projected,” “upcoming,” “will," “would,” “plan,” “intend,” “anticipate,” “approximate,” “expect,” “potential,” “imminent,” and similar references to future periods or the negative of these terms. Not all forward-looking statements contain these identifying words. Examples of forward-looking statements include, among others, statements we make regarding the advancement of oral LUM-201 to Phase 3, the potential for LUM-201 to be the first oral therapeutic for PGHD, and any other statements other than statements of historical fact. We wish we were able to predict the future with 100% accuracy, but that just is not possible. Our forward-looking statements are neither historical facts nor assurances of future performance. You should not rely on any of these forward-looking statements and, to help you make your own risk determinations, we have provided an extensive discussion of risks that could cause actual results to differ materially from our forward-looking statements including risks related to the timing and ability of Lumos Pharma to structure our Phase 3 trial in an effective and timely manner, the ability to initiate and advance a pivotal Phase 3 trial, as well as advance our clinical and corporate strategy in general, our ability to project future cash utilization and reserves needed for contingent future liabilities and business operations, the ability to successfully develop our product candidate, the effects of pandemics, other widespread health problems or military conflicts including the Ukraine-Russia conflict and the Middle East conflict and other risks that could cause actual results to differ materially from those matters expressed in or implied by such forward-looking statements including information in the "Risk Factors" section and elsewhere in Lumos Pharma’s Quarterly Report on Form 10-Q for the period ended September 30, 2024, as well as other subsequent reports filed with the SEC. All of these documents are available on our website. Before making any decisions concerning our stock, you should read and understand those documents. We anticipate that subsequent events and developments will cause our views to change. We may choose to update these forward-looking statements at some point in the future, however, we disclaim any obligation to do so. As a result, you should not rely on these forward-looking statements as representing our views as of any date subsequent to the date of this press release. Investor & Media Contact: Lisa MillerLumos Pharma Investor Relations512-792-5454ir@lumos-pharma.com Photos accompanying this announcement are available athttps://www.globenewswire.com/NewsRoom/AttachmentNg/f1abdd2c-307b-47bb-8cc9-3c555fe00c85https://www.globenewswire.com/NewsRoom/AttachmentNg/b168603b-a009-4bce-a4d1-94367f1568ec Source: Lumos Pharma, Inc.

本文研究结果表明，IGFBP3/miR-34a 轴或能限制IGFBP3在胚胎未分化肺部上皮中的表达，处于假腺期的IGFBP3的逐渐下调或许是机体肺部肺泡分化所必需的。 在人类肺部发育的假腺管型阶段（pseudoglandular stage），原始的支气管芽（primitive bronchial buds）最初是由间质包围的内胚层衍生的上皮内衬中排列的简单小管结构所构成的，这些小管结构会逐渐分支进入气道并开始形成远端上皮小泡结构，而后肺泡II型（AT2）肺部细胞就会首次出现。近日，一篇发表在国际杂志Stem Cell Research & Therapy上题为“Discovering genes and microRNAs involved in human lung development unveils IGFBP3/miR-34a dynamics and their relevance for alveolar differentiation”的研究报告中，来自西班牙巴塞罗那大学等机构的科学家们通过研究发现，IGFBP3蛋白在人类肺部发育过程中扮演着关键角色。 文章中，研究人员利用来自胚胎肺衍生的类器官进行研究，或能为揭示肺部发育开辟新的研究视角，并能为开发针对人类肺部疾病的预防和治疗性策略奠定基础，尤其是新生儿呼吸系统疾病等。IGFBP3是一种在人类机体病理过程（比如癌症）和生理过程中被广泛研究的分子，其往往参与到了细胞增殖、分化和生存的调节过程中，这项最新研究揭示了一种此前未知的方面，即IGFBP3蛋白在人类肺部胚胎发生过程中的重要性。 研究者解释道，IGFBP3能帮助维持肺部上皮细胞（覆盖在肺部内表面的细胞）处于未分化状态，也就是说，其能允许肺部上皮细胞维持发育为多种不同细胞类型的能力。随着肺部发育，IGFBP3的表达必须降低从而才能发生细胞分化，这或许就是正确肺部组织形成所需的过程，随着胚胎发生的进展，这种蛋白质就需要被沉默，这或许揭示了其或许是维持肺部干细胞的关键。这项研究还描述了IGFBP3和miR-34a之间的相互作用，miR-34a是一种在机体基因表达控制过程中扮演关键角色的microRNA样分子，从肺部发育的第8周开始，miR-34a分子就能通过抑制肺部间质和随后上皮中的IGFBP3的产生来发挥作用，从而促进发育过程中这一阶段所需的细胞分化。 全文的图形摘要 这项研究是在人类发育第8周至第12周之间从胚胎肺中所衍生的类器官所产生和建立的，这些类器官能在细胞和分子水平上复制这一器官，在研究中，研究人员观察到，IGFBP3的基因表达与胚胎肺部祖细胞有关，因此，研究人员就需要一种体外模型来复制其表达。基于多能干细胞的类器官能以3D方式在特定组织内繁殖（在这种情况下是肺部粘膜），其能在不同水平上发生相互作用，因此，如今研究人员就能激活细胞的分化过程或沉默特定基因来评估其对肺部发育的影响效应。 此外，相比动物模型而言，这项研究中所使用的人类胚胎能帮助研究人员在理解人类肺部发育方面获得更加准确且更具有生物医学相关性的结果，研究者补充道，尽管动物模型能用于理解机体发育的多个方面，但不同岗位处在结构、功能和重要的发育时间上存在着关键差异。尽管后期研究人员还需要进行更多研究才能开展临床应用，但这项研究的结果为更好的理解呼吸系统疾病开辟了新的途径，尤其是早产儿面临的肺发育不全等疾病，肺发育不全是一种先天性的肺部发育异常，胎儿的肺部发育不完全会导致肺部肺泡数量和大小减少的情况。研究者总结道，理解miR-34a调节IGFBP3表达的分子机制或能促进研究人员未来开发新型靶向性疗法，从而促进肺泡的正常生长并改善患儿机体的肺部功能。 在肿瘤学水平上，IGFBP3或许也能在肺癌中发挥相关作用，尤其是与癌症干细胞相关，如今研究人员已经观察到，肺部肿瘤组织中高水平的IGFBP3或与疾病早期阶段较差的预后相关。因此，研究是否调节IGFBP3就能影响这些癌症干细胞的分化，减缓其迁移、侵袭和转移性生长的速度，或许是一件非常有趣的事情，目前研究人员正在研究肺癌患者机体所衍生的类器官。综上，本文研究结果表明，IGFBP3/miR-34a 轴或能限制IGFBP3在胚胎未分化肺部上皮中的表达，处于假腺期的IGFBP3的逐渐下调或许是机体肺部肺泡分化所必需的。（生物谷Bioon.com） 参考文献： Melissa Acosta-Plasencia,Joan J Castellano,Tania Díaz，et al. Discovering genes and microRNAs involved in human lung development unveils IGFBP3/miR-34a dynamics and their relevance for alveolar differentiation, Stem Cell Res Ther. 2024 Aug 26;15(1):263. doi:10.1186/s13287-024-03883-1.

AUSTIN, Texas, Oct. 30, 2024 (GLOBE NEWSWIRE) -- Lumos Pharma (NASDAQ:LUMO), a clinical stage biopharmaceutical company focused on therapeutics for rare diseases, announced today that updated analyses of data from the Company’s Phase 2 OraGrowtH210 and OraGrowtH212 clinical trials have been accepted for oral presentation at the 62nd Annual European Society for Paediatric Endocrinology Meeting, or ESPE 2024, to be held November 16-18, 2024 in Liverpool, UK. Two abstracts on data from the OraGrowtH Trials evaluating oral LUM-201 for Pediatric Growth Hormone Deficiency (PGHD) will be presented on Sunday, November 17th, by Elżbieta Petriczko, MD, PhD, Pomeranian Medical University, Szczecin, Poland, and on Monday, November 18th, by Peter E. Clayton, MD, University of Manchester, Manchester, UK, respectively. LUM-201 Oral Abstract Presentations: Sunday, November 17th – Session: Free Communications 7: GH and IGFs – 10:50AM Local Time FC7.6 Abstract entitled, Growth, IGF-1 and IGFBP-3 Responses to Oral LUM-201 in OraGrowtH210 and OraGrowtH212 Trials in Pediatric Growth Hormone Deficiency (PGHD) Over 12 to 24 Months on Treatment (Elżbieta Petriczko, MD, PhD, et al) Monday, November 18th – Session: Free Communications 15: Late Breaking – 9:40AM Local Time FC15.2 Abstract entitled, Amount and Pattern of Pulsatile GH Secretion Induced by the Oral Growth Hormone Secretagogue LUM-201 Is Related to Growth and IGF-1 Responses in Moderate Pediatric Growth Hormone Deficiency (PGHD) (Peter E. Clayton, MD, et al) About Lumos Pharma Lumos Pharma, Inc. is a clinical stage biopharmaceutical company focused on the development and commercialization of therapeutics for rare diseases. The Company was founded and is led by a management team with longstanding experience in rare disease drug development. Lumos Pharma’s lead therapeutic candidate, LUM-201, is a novel, oral growth hormone (GH) secretagogue, seeking to transform the ~$4.7B global GH market from injectable to oral therapy. LUM-201 is currently being evaluated in multiple Phase 2 clinical studies in Pediatric Growth Hormone Deficiency (PGHD) and has received Orphan Drug Designation in both the US and EU. For more information, please visit https://lumos-pharma.com/. Investor & Media Contact: Lisa MillerLumos Pharma Investor Relations512-792-5454ir@lumos-pharma.com Source: Lumos Pharma, Inc.