On June 11, 2024 Asgard Therapeutics, a privately held biotech company pioneering in vivo direct cell reprogramming for cancer immunotherapy, reported that it selected Exothera S.A. ("Exothera"), a leading provider of nucleic acids and viral vector development and manufacturing services, for process development up to clinical Phases I/II manufacturing of its candidate AT-108, based on viral vector technology (Press release, Asgard Therapeutics, JUN 11, 2024, View Source [SID1234644248]).

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AT-108 is a first-in-class, off-the-shelf gene therapy that leads to personalized and potent anti-cancer immune responses. AT-108 reprograms cancer cells inside the patient’s body to become conventional Type 1 Dendritic Cells (cDC1s), a rare subset of immune cells, which are critical for effective anti-tumor immunity. These induced cDC1s present the individual’s specific cancer antigens to the immune system, triggering personalized and systemic anti-cancer immune responses.

Exothera will be entrusted with the development and scale-up of a manufacturing process for the drug candidate, including development of analytical methods, GMP-grade material production, and aseptic filling.

Exothera offers a full-service model for viral vector-based biotherapeutics thanks to state-of-the-art technologies, and one of the largest viral vector facilities in Europe (15 000 m² – 161 500 ft²).

Cristiana Pires, Co-founder and Chief Executive Officer of Asgard Therapeutics, said: Following our proof-of-concept studies supporting the lead candidate AT-108, we are very happy to reach process development phase and start CMC activities. We are looking forward to work with the very knowledgeable and skilled technical team at Exothera to progress our pioneering AT-108 towards clinical development.

Hanna Lesch, Chief Technology Officer at Exothera, mentioned: We are proud to support Asgard Therapeutics in bringing these revolutionary therapeutics closer to the patients. Over the years we gained extensive experience with virus-based therapeutics production – both in suspension and in fixed bed bioreactors – and we are confident that we will use this expertise to help Asgard Therapeutics achieve clinical phase success.

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 Ono Pharmaceutical, Co., Ltd. (Chairman and CEO: Gyo Sagara, "Ono") reported that it has successfully completed the tender offer, previously announced on April 30, 2024 to acquire all outstanding shares of common stock of a US biopharmaceutical company, Deciphera Pharmaceuticals, Inc. (Nasdaq: DCPH, CEO: Steven L. Hoerter, "Deciphera") for US$25.60 per share (total amount of approximately US$2.4 billion) net to the seller in cash, without interest thereon and less any applicable withholding taxes, through its wholly owned subsidiary, Topaz Merger Sub, Inc. ("Merger Sub"), established in the State of Delaware, United States, solely for the purpose of engaging in the transactions contemplated in the Merger Agreement (Press release, Deciphera Pharmaceuticals, JUN 11, 2024, View Source [SID1234644250]).

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The tender offer commenced on May 13, 2024, New York City time, and, as set forth below, expired at one minute after 11:59 p.m., New York City time, on June 10, 2024.

On June 11, 2024, following the completion of the tender offer, Merger Sub merged with and into Deciphera with Deciphera continuing as the surviving corporation and a wholly owned subsidiary of Ono. In connection with the acquisition, Deciphera shares ceased to be traded on Nasdaq as of the date of closing of the acquisition and shares of Deciphera’s common stock will be delisted from Nasdaq.

"We are very pleased to welcome Deciphera into the family," said Gyo Sagara, Chairman and CEO of Ono. "Through this acquisition, we will leverage Deciphera’s excellent research and development capabilities in the oncology field and its sales power in Europe and the United States, and work to further accelerate the expansion of our pipeline and global expansion, which are part of our growth strategies."

"We are excited to enter a new phase as part of the family of Ono Pharmaceuticals, that has as its mission to contribute to society through the discovery and development of innovative drugs, under the corporate philosophy "Dedicated to the Fight against Disease and Pain,"" said Steven L. Hoerter, President and CEO of Deciphera. "By fully leveraging the research and development capabilities and commercialization platforms of both companies, we look forward to significantly contributing to the growth of the Ono Group as a global specialty pharma company."

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 Molecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin therapeutics and Orano Med, a clinical stage radiopharmaceutical company developing targeted alpha therapies with lead-212 (212Pb), reported the debut of their lead Radio-DARPin therapy (RDT) candidate MP0712, targeting DLL3, in an oral presentation (Press release, Molecular Partners, JUN 11, 2024, View Source [SID1234644228]). The data presented today provide strong support for MP0712’s clinical development in small-cell lung cancer (SCLC) and other DLL3+ neuroendocrine tumors. MP0712 features 212Pb as a potent therapeutic payload. The data were presented today at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2024 Annual Meeting taking place June 8-11 in Toronto, Canada.

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"Three years ago, we started our venture into the radiotherapy space. We have made tremendous progress with our Radio-DARPins and are proud to present MP0712, our first RDT development candidate targeting DLL3 delivering and 212Pb to kill the tumor, in partnership with Orano Med," said Patrick Amstutz, Ph.D., Molecular Partners’ Chief Executive Officer. "We have made key learnings how to reduce kidney accumulation and increase tumor uptake. We are now exploiting the long-known DARPin advantages to a full pipeline of candidates addressing high medical need. Kudos to both the Orano Med and Molecular Partners team for advancing the science to make this happen."

"We are extremely excited with the first preclinical results of the MP0712 program, which confirm the potential of the combination between Molecular Partners’ targeting technology and 212Pb, an isotope perfectly suited for targeted alpha therapy. We eagerly anticipate advancing the drug’s development and initiating clinical trials to provide solutions for patients with unmet medical needs," said Julien Dodet, CEO of Orano Med.

MP0712 is the first high-affinity DLL3-targeting RDT combining the advantages of DARPins as small protein-based delivery vectors and the short-lived alpha particle-emitting radioisotope 212Pb. DLL3 is expressed in >85% of SCLC patients and in other neuroendocrine tumors, while its expression in healthy tissues is low, making it a priority target for radiopharmaceutical therapy. SCLC is an aggressive form of lung cancer, with a poor five-year survival prognosis and a high unmet need for patients.

The preclinical package presented at SNMMI includes in vivo data demonstrating strong and homogeneous tumor uptake of 212Pb-DLL3 RDT, as well as significant and durable inhibition of tumor growth at clinically-relevant doses. The safety results seen across the tested dosing levels in mice suggest a favorable safety profile and potential for clinical use. 212Pb-DLL3 RDT candidates were engineered by tuning their biophysical properties to achieve an optimal safety/antitumor activity profile in vivo. The selected lead candidate, MP0712, demonstrated a promising biodistribution profile in mouse xenograft tumor models, with close to 60% of injected dose detectable in the tumor and encouraging tumor to kidney ratios over two. The replicable DARPin learnings from the development of MP0712, as well as additional platform improvements, are being taken forward to the broader RDT portfolio.

The intrinsic properties of DARPins, such as small size, high affinity and selectivity, and a broad range of potential targets, make them ideal vector candidates for radiopharmaceutical therapeutics. Historically, small protein-based vectors faced challenges with kidney accumulation and toxicity, as well as suboptimal tumor uptake. Molecular Partners has evolved its RDT platform to address these limitations with its half-life extension technologies and surface engineering approaches, while preserving the advantages of the small protein format. In addition, Molecular Partners’ DARPin candidates have been clinically validated with over 2500 patients treated worldwide and multiple DARPin mechanisms have been demonstrated as biologically active in for different indications, contributing to validation of the drug class and Molecular Partners as leader in the field of DARPin engineering and development.

Details of the presentation summarizing the MP0712 preclinical data at the SNMMI 2024 Annual Meeting can be found below. The presentation will be made available on Molecular Partners’ website after the presentation.

Presentation Title: Lead-212 Radio-DARPin Therapeutic (RDT) targeting delta-like ligand 3 (DLL3) shows promising preclinical antitumor efficacy and tolerability in small cell lung cancer (SCLC)
Session: IS09 Integrated Session: Radionuclides (CMIIT/RPSC);
Timing: 11 June 2024; 8:00–9:15 am EDT