SPARC

MitoCareX Bio dedicates efforts to creating a predictive AI model to predict small molecules more efficiently TEL AVIV, Israel, March 21, 2024 (GLOBE NEWSWIRE) -- SciSparc Ltd. (Nasdaq: SPRC) ("Company" or "SciSparc"), a specialty clinical-stage pharmaceutical company focusing on the development of therapies to treat disorders of the central nervous system, announced that MitoCareX Bio Ltd. ("MitoCareX"), the Company’s venture with Dr. Alon Silberman that focuses on drug discovery and the development of cancer therapeutics by targeting the mitochondrial SLC25 protein family, had virtually screened millions of small molecules by using its computationally advanced drug discovery platform, which resulted in the identification of several molecules that could be used for potential anti-cancer treatments. As previously announced by the Company on March 12, 2024, by using its in-vitro screening systems related to the mitochondria, MitoCareX corroborated its virtual findings by confirming the anti-cancer biological activity of several small molecule structures. Additionally, by utilizing the extensive virtual data generated, MitoCareX is working towards creating a predictive AI model. This model is expected to enable MitoCareX to navigate broader chemical spaces more efficiently, with the goal of uncovering more novel anti-cancer scaffolds that target its SLC25 protein of interest. About SciSparc Ltd. (Nasdaq: SPRC): SciSparc Ltd. is a specialty clinical-stage pharmaceutical company led by an experienced team of senior executives and scientists. SciSparc’s focus is on creating and enhancing a portfolio of technologies and assets based on cannabinoid pharmaceuticals. With this focus, the Company is currently engaged in the following drug development programs based on THC and/or non-psychoactive CBD: SCI-110 for the treatment of Tourette Syndrome, for the treatment of Alzheimer's disease and agitation; SCI-160 for the treatment of pain; and SCI-210 for the treatment of ASD and status epilepticus. The Company also owns a controlling interest in a subsidiary whose business focuses on the sale of hemp seeds’ oil-based products on Amazon Marketplace. Forward-Looking Statements: This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995 and other Federal securities laws. For example, SciSparc is using forward-looking statements when it discusses that MitoCareX is working towards creating a predictive AI model and that such model is expected to enable MitoCareX to navigate broader chemical spaces more efficiently, with the goal of uncovering more novel anti-cancer scaffolds that target the SLC25 protein of interest. Historical results of scientific research and clinical and preclinical trials do not guarantee that the conclusions of future research or trials will suggest identical or even similar conclusions. Because such statements deal with future events and are based on SciSparc's current expectations, they are subject to various risks and uncertainties and actual results, performance or achievements of SciSparc could differ materially from those described in or implied by the statements in this press release. The forward-looking statements contained or implied in this press release are subject to other risks and uncertainties, including those discussed under the heading "Risk Factors" in SciSparc's Annual Report on Form 20-F filed with the SEC on May 1, 2023, and in subsequent filings with the U.S. Securities and Exchange Commission. Except as otherwise required by law, SciSparc disclaims any intention or obligation to update or revise any forward-looking statements, which speak only as of the date they were made, whether as a result of new information, future events or circumstances or otherwise. Investor Contact:IR@scisparc.comTel: +972-3-6167055

PRINCETON, NJ / ACCESSWIRE / February 29, 2024 / Sonnet BioTherapeutics Holdings, Inc., (NASDAQ:SONN) a clinical-stage company developing targeted immunotherapeutic drugs for cancer, announced today the publication of clinical data on SON-1010 in Frontiers in Immunology. SON-1010, Sonnet's lead proprietary monofunctional compound, combines the company's fully-human albumin-binding (FHAB) construct with single-chain interleukin 12 (IL‑12). The paper, entitled "A phase I trial of SON-1010, a tumor-targeted, interleukin-12-linked, albumin-binding cytokine, shows favorable pharmacokinetics, pharmacodynamics, and safety in healthy volunteers", demonstrated safety and tolerability up to 300 ng/kg as a single ascending dose. In the B16F10 melanoma model, a single dose of SON-1010 results in a marked reduction of tumor growth that was concomitant with increased IFNg, along with augmented immune cell numbers and activity in the tumor microenvironment (TME). The study of SON‑1010 in healthy volunteers, called SB102 (NCT05408572), was first announced in July 2022 and was done in parallel with the ongoing SB101 study in cancer patients (NCT05352750). The results from SB102 provide the initial ‘desensitizing dose' for further dose escalation of the maintenance dose in SB101, to establish the maximum tolerated dose for this molecule. "The publication of these data is an important milestone for Sonnet that provides additional scientific validation of our FHAB technology." said Pankaj Mohan, Ph.D., Founder and CEO of Sonnet. "The SB102 study was designed to elucidate the PK and PD of SON-1010 in normal, healthy volunteers, and shows that the drug is safe in the dose range tested, while also providing an appreciably extended half-life. When combined with checkpoint inhibitors, we hypothesize that the targeted immune enhancing components of the SON-1010 mechanism have the potential to turn cold tumors hot. We also believe that our pipeline, which includes compounds with bifunctional combinations of Interleukins 15 and 18, could potentially prove useful in combination with cell-based therapies. We are diligently pursuing these applications, as well." While doses above 100 ng/kg were tolerated, participants generally experienced more treatment-emergent adverse effects (TEAEs) than those receiving the lowest dose of 50 ng/kg. All TEAEs were transient and were consistent with published experience using recombinant IL‑12. More precise pharmacokinetic (PK) and pharmacodynamic (PD) data can be obtained using this non-genotoxic cancer therapy in healthy individuals, without a background of immunosuppression. PK analysis showed two-compartment elimination in SB102 with a mean half-life of 104 hours, compared with one-compartment elimination in SB101, which correlated with prolonged but controlled and dose-related increases in IFNg. This is evidence for target-mediated drug disposition (TMDD), which implies delivery to and retention of SON-1010 in tumor tissue. There were minimal responses with other cytokines and no evidence of cytokine release syndrome. "IL-12 has been studied in healthy volunteers in the past and has shown great promise in animal models of cancer treatment for decades, yet developmental progress in human trials has typically been hindered by toxicity before the therapeutic dose can be reached." said Richard Kenney, M.D., Sonnet's Chief Medical Officer. "Extending the PK by binding to the neonatal Fc receptor (FcRn), combined with targeting retention in the TME through binding to gp60 and SPARC, contributes to TME localization of SON-1010. This may be the key to enhancing the therapeutic window and inducing successful immune responses in the TME, as the PD will also be extended to allow better activation of immune cell penetration and replacement of immune inhibitors." The manuscript can be accessed through the following link: About SON-1010 SON-1010 is an immunotherapeutic drug candidate that links unmodified single-chain human IL-12 with the albumin-binding domain of the single-chain antibody fragment FHAB. The FHAB single chain was selected to bind well at normal pH, as well as at an acidic pH that is typically found in the tumor microenvironment (TME). The FHAB technology targets tumor and lymphatic tissue, providing a mechanism for dose-sparing, enhanced pK, and an opportunity to improve the safety and efficacy pro IL-12. A variety of other potent immunomodulators can be combined with the platform to orchestrate a robust immune response to many cancers and pathogens. Given the types of proteins induced in the TME, such as Secreted Protein Acidic and Rich in Cysteine (SPARC), several types of cancer such as non-small cell lung cancer, melanoma, colorectal cancer, head and neck cancer, sarcoma, and some gynecological cancers are particularly relevant for this approach. SON-1010 is designed to deliver IL-12 to local tumor tissue, with the intention of turning ‘cold' tumors ‘hot' by stimulating IFNg, which activates both innate and adaptive immune cells in the TME, as well as increasing the production of Programed Death Ligand 1 (PD-L1) on tumor cells. About Sonnet BioTherapeutics Holdings, Inc. Sonnet BioTherapeutics is an oncology-focused biotechnology company with a proprietary platform for innovating biologic drugs of single or bifunctional action. Known as FHAB (Fully Human Albumin Binding), the technology utilizes a fully human single chain antibody fragment (scFv) that binds to and "hitch-hikes" on human serum albumin (HSA) for transport to target tissues. Sonnet's FHAB was designed to specifically target tumor and lymphatic tissue, with an improved therapeutic window for optimizing the safety and efficacy of immune modulating biologic drugs. FHAB is the foundation of a modular, plug-and-play construct for potentiating a range of large molecule therapeutic classes, including cytokines, peptides, antibodies, and vaccines. Forward-Looking Statements This press release contains certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section21E of the Securities Exchange Act of 1934 and Private Securities Litigation Reform Act, as amended, including those relating to the Company's cash runway, the Company's product development, clinical and regulatory timelines, market opportunity, competitive position, possible or assumed future results of operations, business strategies, potential growth opportunities and other statements that are predictive in nature. These forward-looking statements are based on current expectations, estimates, forecasts and projections about the industry and markets in which we operate and management's current beliefs and assumptions. These statements may be identified by the use of forward-looking expressions, including, but not limited to, "expect," "anticipate," "intend," "plan," "believe," "estimate," "potential, "predict," "project," "should," "would" and similar expressions and the negatives of those terms. These statements relate to future events or our financial performance and involve known and unknown risks, uncertainties, and other factors which may cause actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Such factors include those set forth in the Company's filings with the Securities and Exchange Commission. Prospective investors are cautioned not to place undue reliance on such forward-looking statements, which speak only as of the date of this press release. The Company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Sonnet BioTherapeutics Investor Contact: Jack Yauch Solebury Strategic Communications 862-754-1024 jyauch@soleburystrat.com SOURCE: Sonnet BioTherapeutics, Inc. View the original press release on accesswire.com

本文为转化医学网原创，转载请注明出处 作者：Sophia 导读： 转移是肺癌相关死亡的主要原因，但控制肺肿瘤转移的机制仍未完全阐明。SE 易位 （SET） 在肺肿瘤中过表达，并与不良预后相关。 2024年2月14日，中国医学科学院北京协和医学院基础医学研究所王冬来课题组在《Nature Communications》上发表题为“Oncoprotein SET-associated transcription factor ZBTB11 triggers lung cancer metastasis”的研究文章， 研究证明了 ZBTB11 是一种关键的转移调节因子，并揭示了 ZBTB11 调节肺肿瘤转移的多种机制。 https://www.nature.com/articles/s41467-024-45585-5 研究背景 01 最新的全球癌症统计数据显示，虽然肺癌发病率已降至第二位，但仍然是癌症死亡的主要原因。肺癌在组织学上可分为小细胞肺癌（SCLC）和非小细胞肺癌（NSCLC），后者可进一步分为腺癌（LUAD）、鳞状细胞癌（LUSC）、大细胞癌等。在所有类型的肺癌中，超过40%是腺癌，转移是恶性肿瘤晚期的标志，是患者肺癌相关死亡的主要原因。然而， 肺癌转移的调控机制仍不完全清楚。 癌蛋白 SET 最初是在急性未分化白血病 （AUL） 研究中发现的，在研究染色体易位引起的 DNA 断点时发现了一种新的致癌 SET-CAN 融合基因。条件基因敲除小鼠模型中 SET 表达的完全丧失揭示了胚胎致死表型，证明了 SET 在调节正常发育中的关键作用。更引人注目的是，SET过表达是包括肺癌在内的不同类型癌症中的常见事件，这表明SET在成体细胞中的异常表达有助于肿瘤的发生和/或进展。通过单独或联合策略靶向异常 SET 可能会触发细胞质和细胞核参与的肿瘤机制，包括肺癌，干预。然而， 决定 SET 用于肺癌转移调节的细胞核内的主要 TFs 仍然不明确。 据报道，ZBTB11 参与了长链非编码 RNA （lncRNA） DUBR 介导的肺癌细胞迁移和侵袭，这表明 ZBTB11 在肺癌进展过程中具有潜在作用。然而， ZBTB11 在肺癌中控制的精确转录谱、调控网络和生物学后果在很大程度上仍然未知。 研究进展 02 为了研究肺癌细胞中 SET 和 ZBTB11 之间的功能相互作用， 我们试图鉴定 SET 介导的 ZBTB11 直接靶基因的调控。 为此，我们首先在SET耗竭96小时后通过RNA-seq评估H1299细胞中的差异表达基因（图3a）。如图 3b 所示，我们鉴定了 164 和 145 个基因，它们在 SET 敲低时分别上调和下调。同样，大多数SET调节的基因也富集在蛋白质编码类别中（~67%，207，图3c）。基于这些数据集，我们发现了 35 个推定的 ZBTB11 直接靶基因，这些基因受 SET（图3d）的共调控。有趣的是，这些基因可以清楚地分为两组：18 个基因在 SET 和 ZBTB11 耗竭时被转录抑制，17 个基因在 SET 和 ZBTB11 耗竭时被转录激活（图3e）。SET/ZBTB11 共调控靶基因的转录谱表明 SET 可能与 ZBTB11 在转录调控方面具有功能协同作用。值得注意的是，GO分析显示，由共调控靶基因富集的顶级生物过程是“细胞外基质组织”，与ZBTB11调控基因富集的生物过程完全相同（图3f）。此外，使用靶标特异性引物的RT-qPCR测定进一步证实，参与细胞外基质组织的MMP9、MMP19、SPARC、PECAM1、SPP1和COL14A1基因确实在H1299细胞中受到SET和ZBTB11的共同调节（图3g）。在 H1975 肺癌细胞中，这些基因在 SET 和/或 ZBTB11 敲低时的类似转录调控也被概括。 SET与ZBTB11在转录调控方面合作 总的来说，这些数据表明 SET 与 ZBTB11 在转录调控中合作，并促使我们关注 SET-ZBTB11 蛋白复合物在肿瘤发生和进展时调节细胞外基质相关生物过程的潜在作用。 研究结果 03 在这项研究中，我们将 ZBTB11 确定为细胞核中癌蛋白 SET 的结合伙伴。对 ChIP-seq 和 RNA-seq 的综合分析表明，ZBTB11 在肺癌细胞中充当转录因子。SET通过作为辅因子与ZBTB11合作进行转录调控，SET和ZBTB11之间的相互作用在调节肺癌细胞的转移行为中至关重要。从机制上讲， 我们发现 MMP9 是有助于 SET-ZBTB11 复合物介导的转移调节的主要下游效应子。此外，ZBTB11 通过转录抑制 PRRG2 表现出一种作用模式，与 YAP1 的激活建立连接，以 SET-ZBTB11 复合物非依赖性方式促进肺肿瘤转移。更重要的是，ZBTB11的条件性敲除可显著抑制体内遗传病变诱导的原发性肺肿瘤的远端转移。 综上所述，我们的研究表明，SET结合伙伴ZBTB11在调节肺肿瘤转移中起着关键作用。 参考资料： https://www.nature.com/articles/s41467-024-45585-5 注：本文旨在介绍医学研究进展，不能作为治疗方案参考。如需获得健康指导，请至正规医院就诊。 热门·直播/活动 🕓 上海｜3月01日-02日 ▶第三届长三角单细胞组学技术应用论坛暨空间组学前沿论坛将在上海召开，诚邀您的参与！ 点击对应文字 查看详情