On June 11, 2024 Moleculent AB, a company pioneering technology to study the communication between cells in human tissue, reported the closing of its oversubscribed $26 million Series A financing (Press release, Moleculent, JUN 11, 2024, View Source [SID1234644273]). The round was led by ARCH Venture Partners (ARCH) and co-led by Eir Ventures with participation from the company’s existing investors. ARCH’s Patrick Weiss has been appointed Chairman. Sean Kendall from ARCH, together with Magnus Persson from Eir Ventures, have also joined the company’s Board of Directors.

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Moleculent’s functional biology platform detects cell-cell interactions and profiles their communication directly within their tissue environment. This novel approach allows scientists to see how healthy cells function and how diseased cells differ at a complex, networked level. A complete picture of the cell-cell communication in a tumor, for example, offers a practical understanding of the signaling pathways and molecular mechanisms involved in drug response. Studying cell-cell interactions between many different receptors and ligands, in a tissue context, represents a paradigm shift in understanding biological systems by enabling scientists to see a more comprehensive picture and to decode the cell-cell conversations and disease pathways.

"Analysis of DNA, as well as RNA and protein expression inform us about the building blocks of a cell but do not directly measure how cells are working together. Understanding cell-cell communication networks in tissues has the potential to bring us into a new era of understanding functional biology and human disorders," said Olle Ericsson, PhD, co-founder and Chief Executive Officer of Moleculent. "The Moleculent platform has been designed to allow scientists to uncover radical new insights into the cellular level of human biology and pathology. We are very happy to partner with ARCH Venture Partners and Eir Ventures to bring this enabling platform to the scientific community."

Moleculent is led by a team of industry veterans with expertise in developing and globally commercializing life science tools at leading companies including Halo Genomics (acquired by Agilent), Vanadis Diagnostics (acquired by Perkin Elmer), and Spatial Transcriptomics (acquired by 10x Genomics).

"Spatial mapping technologies transformed our understanding of cellular neighborhoods, and the next frontier is to measure the critical communications between networks of individual cells. Moleculent will enable scientists to decipher this communication to better understand functional human biology," said Weiss. "I am honored to chair the Moleculent Board and look forward to working with this exceptional team of experienced entrepreneurs and technology developers to change how we understand and diagnose disease in the coming decade."

On June 11, 2024 Incyte Corporation (Nasdaq: INCY) ("Incyte" or the "Company") reported the preliminary results of its modified "Dutch auction" tender offer to purchase up to $1.672 billion in value of shares of its common stock, which expired at 12:00 midnight, at the end of the day, New York City time, on June 10, 2024 (Press release, Incyte, JUN 11, 2024, View Source [SID1234644271]).

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Based on the preliminary count by Computershare Trust Company, N.A., the depositary for the tender offer, a total of approximately 29.8 million shares of Incyte’s common stock were properly tendered and not properly withdrawn at or below the purchase price of $60.00 per share, including approximately 14.8 million shares that were tendered through notice of guaranteed delivery. Incyte has been informed by the depositary that the preliminary proration factor for the shares to be purchased by Incyte pursuant to the tender offer is approximately 93.4 percent.

In accordance with the terms and conditions of the tender offer and based on the preliminary count by the depositary, the Company expects to purchase approximately 27.9 million shares of its common stock through the tender offer at a purchase price of $60.00 per share, for a total cost of approximately $1.672 billion, excluding fees and expenses relating to the tender offer. These shares represent approximately 12.4 percent of the Company’s total outstanding shares of common stock as of June 7, 2024.

As previously announced, on May 12, 2024, Incyte entered into a separate stock purchase agreement with Julian C. Baker (a member of Incyte’s Board of Directors), Felix J. Baker, and entities affiliated with Julian C. and Felix J. Baker, including funds advised by Baker Bros. Advisors LP (collectively, the "Baker Entities"), under which the Baker Entities agreed not to tender or sell any shares in the tender offer and instead agreed to sell to the Company, following completion of the tender offer, a pro rata number of shares at the same price per share as will be paid by the Company in the tender offer, such that the Baker Entities’ aggregate percentage ownership in the Company will be substantially the same as prior to the tender offer. As such, the Company expects to repurchase a total of approximately 33.3 million shares of its common stock through the tender offer and the stock purchase agreement at a price of $60.00 per share, for a total cost of approximately $2.0 billion, excluding fees and expenses. These shares represent approximately 14.8 percent of the Company’s total outstanding shares of common stock as of June 7, 2024.

The number of shares expected to be purchased in the tender offer and under the stock purchase agreement and the purchase price per share are preliminary and subject to change. The preliminary information contained in this press release is subject to confirmation by the depositary and is based on the assumption that all shares tendered through notice of guaranteed delivery will be delivered within the required one business day period. The final number of shares to be purchased in the tender offer and the final purchase price per share will be announced following the expiration of the guaranteed delivery period and the completion by the depositary of the confirmation process. Payment for the shares accepted for purchase pursuant to the tender offer, and the return of all other shares tendered and not purchased, will occur promptly following the completion of the confirmation process. The Company expects to fund the purchase of shares in the tender offer and pursuant to the stock purchase agreement with the Baker Entities, together with all related fees and expenses, with cash on hand.

The dealer manager for the tender offer is Goldman Sachs & Co. LLC. D.F. King & Co., Inc. is serving as information agent for the tender offer. Stockholders who have questions or would like additional information about the tender offer may contact D.F. King & Co., Inc. toll-free at (866) 864-4943.

On June 11, 2024 Eilean Therapeutics AU Pty Ltd, a biopharmaceutical company dedicated to discovering and developing best-in-class and first-in-class small molecule inhibitors to target escape mutations in hematologic and solid malignancies, reported that it has joined The Leukemia & Lymphoma Society (LLS) in the groundbreaking collaborative Beat AML Master Clinical Trial (Press release, Eilean Therapeutics, JUN 11, 2024, View Source;lymphoma-societys-groundbreaking-beat-aml-master-clinical-trial-302168959.html [SID1234644270]).

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Eilean’s investigational agent, lomonitinib (ZE46-0134) has been selected for a new trial arm for patients with FLT3 mutated relapsed/refractory (R/R) acute myeloid leukemia (AML). Lomonitinib is a highly potent and selective pan-FLT3/IRAK4 inhibitor that targets clinically relevant FLT3 mutations and putative escape pathways. Given the excellent safety profile (with no cytological changes) and ability to rapidly reach steady state, target engagement exposures in a healthy volunteer study, it is anticipated that lomonitinib will have a deeper response (i.e. more CR/CRh) and longer duration of response in R/R AML patients and eventually expand to be the best-in-class FLT3 inhibitor. This will be Beat AML’s first phase 1 sub study, as well as its first precision medicine study in patients whose AML has relapsed or not responded to previous therapies.

"The Beat AML Master Trial provides a unique opportunity to contribute to the advancement of science in AML and evaluate the potential of lomonitinib in FLT3 mutated relapsed refractory AML," commented Iain Dukes, Chief Executive Officer of Eilean Therapeutics.

Beat AML is among the first cancer clinical trials to be sponsored by a nonprofit. It brings together a broad global collaboration of the best and brightest clinicians, cancer centers, pharmaceutical companies, and operational and technology partners, all unified to fundamentally change the treatment approach to AML. The trial has generated impressive results, showing superior survival rates and better quality of life when patients receive targeted treatment matched to the genetic mutations or their blood cancer in place of standard-of-care chemotherapy treatment.

"This partnership with Eilean is exactly what LLS envisioned when we began the Beat AML trial," said Ashley Yocum, Ph.D., LLS executive research lead for Beat AML. "Working with partners like Eilean to evaluate their new and potentially breakthrough approaches to AML treatment in the Beat AML framework will speed the process of bringing new treatments to both newly diagnosed patients and those previously treated with other therapies."

About Lomonitinib
Lomonitinib is a highly potent and selective inhibitor of FLT3 ITD, TKD and other clinically relevant FLT3 mutations, as well as IRAK4. FLT3 mutations are the most frequently identified mutations in AML. There are two main mechanisms of resistance to FLT3 inhibitors: the FLT3-ITD-F691L mutation deemed the "gatekeeper" mutation that confers resistance to all currently approved FLT3 inhibitors and the activation of the IRAK4 escape pathway. Lomonitinib inhibits both resistance mechanisms.

On June 11, 2024 Laminar Pharmaceuticals S.A., a clinical-stage biotechnological company developing novel therapies to treat diverse pathologies with unmet clinical needs, reported the recruitment of patients for the CLINGLIO (NCT04250922) study has been closed after 140 adult patients have been successfully enrolled (Press release, Laminar Pharma, JUN 11, 2024, View Source [SID1234644269]). The CLINGLIO study is a multinational, phase 2b/3, randomized, placebo-controlled, double-blind clinical trial evaluating idroxioleic acid in combination with Standard of Care (combined tumour resection and chemoradiotherapy) for the treatment of newly diagnosed glioblastoma patients. The CLINGLIO trial, funded by a European Commission Grant (H2020) is being carried out in 21 hospitals in Spain, Italy, France, and United Kingdom. The investigational study drug, idroxioleic acid (LAM561, sodium; 2-OHOA) is a synthetic fatty acid with a novel therapeutic approach, administrated orally to treat this devastating type of cancer.

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"We are pleased to announce that the pivotal phase 2b/3 trial recruitment is completed, as this means that the results and outcome of the trial will be soon available," said Adrian McNicholl, Chief of Clinical Operations at Laminar Pharmaceuticals. The trial is expected to reach the trigger event for interim analysis in July 2024, which would provide an unblinded readout the last quarter of this year. "If idroxioleic acid is able to show compelling evidence demonstrating significant progression free survival benefit with overall survival, it could imply the first addition to the Standard of Care for glioblastoma patients since the approval of Temozolomide in 2005, 19 years ago." These unblinded results will be submitted for EMA evaluation for Conditional Marketing Authorization in early 2025, and the trial will continue until final analysis of survival in 2026.

Pablo Escribá, CEO of Laminar Pharmaceuticals, said: "The completion of the recruitment is a huge milestone in our clinical trial and in the development of this potential new therapy for glioblastoma patients. We are excited about the possibility of offering a new treatment available for this fatal disease, which has some of the clearer unmet needs across the oncology field".

The CLINGLIO trial, which was initiated in December 2019, has enrolled 140 participants across 4 countries in Europe. Those patients were randomized 1:1 versus placebo. Idroxioleic acid or placebo is added to Standard of Care, and continued for as long as the tumour does not progress. Idroxioleic acid has shown a favorable safety profile in pre-clinical and clinical trials so far. Additionally, no safety concerns were raised by an Independent Data Monitoring Committee (IDMC) who recommended "continue without modifications" after unblinded reviews of the available safety and efficacy data. The trial will continue until the final analysis of overall survival.

The CLINGLIO trial is considered pivotal in that results showing significant clinical benefit could be sufficient for a request for conditional marketing authorization in the EU late this year; and potential full marketing authorization in 2026, for which enabling pre-submission interactions with the EMA have been initiated.

On June 11, 2024 Oncotelic Therapeutics, Inc (OTCQB:OTLC) reported that its CEO- Dr. Vuong Trieu will speak at the 20th Annual Congress of International Drug Discovery Science & Technology (IDDST) (Europe), June 17-19, 2024 at Budapest, Hungary (Press release, Oncotelic, JUN 11, 2024, View Source [SID1234644268]).

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Title: TGFB2 therapeutic for the treatment of CRC, GBM, and PDAC

Anirudh Kolanu, K. Khuranu, A. Mehta, T. Sanil1, G. Trieu, and Dr. Vuong Trieu*

Abstract: OT-101, an antisense against TGFB2, is being tested in phase 3 clinical trials for pancreatic cancer and glioblastoma. It was previously reported to have robust clinical activity in those indications as well as in melanoma. Here, we explore the potential application of OT-101 in colorectal cancer (CRC) through the analysis of CRC patients treated with OT-101 during its clinical development, as well as through bioinformatic. Intravenous therapy with OT-101 in melanoma, colorectal cancer, and pancreatic cancer was evaluated in P001- a phase I/II study. A total of 62 patients were enrolled; 38 patients with pancreatic cancer, 19 patients with melanoma, and 5 patients with colorectal cancer. Full pharmacokinetic evaluation of these patients demonstrated a drug effect with improved progression-free survival (PFS) with increased drug exposure defined by AUClast. The CRC patients were heavily pretreated with multiple lines of previous therapies (4,5,5,6,8), reflected in short overall survival times (2.1, 2.5, 3.0, 5.7, 7.3 months). High AUC exhibited a doubling of PFS to 84 days versus 40 days. A sample of 4259 colorectal adenocarcinoma cancer patients from cbioportal was analyzed. The low expression of two genes: TGFB2 and TGFM6 improved OS. The combination of TGFB2 and TGFM6 was superior to TGFB2 or TGFM6 alone, with TGFB2 being the dominant factor. There was strong but not overlapping sexual dimorphism among the two genes separately but not when used together. The TGFB/TGM6 impact was most significant on Mesenchymal CMS- increasing median survival from 42 months with high TGFB2/TGM6 to 132 months with low TGFB2/TGM6- a threefold improvement with a highly significant p-value of 1.4e-5. Statistical significance was not observed when the genes were used separately. Suppression of TGFB2, i.e., through OT-101, is a potential approach for the treatment of CRC.especially OT-101 treatment of TGM6 low patients.

"It is gratifying to identify what we think is the fundamental role of TGFM6 and TGFB2 in cancer," said Dr. Vuong Trieu, CEO and Chairman of Oncotelic. "Considering the work done here by our interns drawn from local high schools through Brush&Key Foundation for Young Artist, I am impressed at the quality of their outputs."

Supporting publications are as below:

1) Transforming Growth Factor Beta 2 (TGFB2) mRNA Levels, in Conjunction with Interferon-Gamma Receptor Activation of Interferon Regulatory Factor 5 (IRF5) and Expression of CD276/B7-H3, Are Therapeutically Targetable Negative Prognostic Markers in Low-Grade Gliomas.Trieu V, Maida AE, Qazi S. Cancers (Basel). 2024 Mar 19;16(6):1202. doi: 10.3390/cancers16061202. PMID: 38539537.

2) Transforming Growth Factor Beta 2 (TGFB2) and Interferon Gamma Receptor 2 (IFNGR2) mRNA Levels in the Brainstem Tumor Microenvironment (TME) Significantly Impact Overall Survival in Pediatric DMG Patients. Qazi S, Talebi Z, Trieu V. Biomedicines. 2024 Jan 15;12(1):191. doi: 10.3390/biomedicines12010191. PMID: 38255296.

3) High Intra-Tumor Transforming Growth Factor Beta 2 Level as a Predictor of Poor Treatment Outcomes in Pediatric Diffuse Intrinsic Pontine Glioma. Uckun FM, Qazi S, Trieu V. Cancers (Basel). 2023 Mar 9;15(6):1676. doi: 10.3390/cancers15061676. PMID: 36980562.