On June 17, 2024 iTeos Therapeutics, Inc. (Nasdaq: ITOS) ("iTeos"), a clinical-stage biopharmaceutical company pioneering the discovery and development of a new generation of immuno-oncology therapeutics for patients, and its development partner GSK, reported to have initiated the first, global Phase 3 registration study of belrestotug + dostarlimab doublet versus placebo + pembrolizumab in patients with previously untreated, unresectable, locally advanced or metastatic PD-L1 selected non-small cell lung cancer (NSCLC) (Press release, iTeos Therapeutics, JUN 17, 2024, View Source [SID1234644400]).

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"With the initiation of the first Phase 3 study for belrestotug, we are entering a monumental stage in our journey to develop a world-leading oncology company. Nearly 70% of patients with first-line PD-L1 high non-small cell lung cancer rely upon a chemotherapy-free regimen. We believe belrestotug + dostarlimab are poised to potentially advance the therapeutic regimen in this setting and establish new benchmarks," said Michel Detheux, Ph.D., president and chief executive officer of iTeos. "Based on our high-quality doublet exceeding its pre-defined efficacy criteria for clinically relevant activity in an interim assessment from the Phase 2 GALAXIES Lung-201 study, we believe initiating the Phase 3 program with this patient population will serve as the foundation to our broader strategy and marks our first step in building a franchise."

The randomized, double-blind, placebo-controlled, multicenter trial will enroll approximately 1,000 patients with previously untreated, unresectable, locally advanced or metastatic PD-L1 selected NSCLC in North America, South America, Europe and Asia. The primary endpoints of the trial are progression free survival and overall survival. In the GALAXIES Lung-301 trial, patients will be randomized 1:1 to either an intravenous infusion of the belrestotug + dostarlimab doublet or placebo + pembrolizumab.

In May 2024, iTeos announced an interim assessment of the Phase 2 GALAXIES Lung-201 study of the belrestotug + dostarlimab doublet in previously untreated, locally advanced, or metastatic PD-L1 selected NSCLC exceeded pre-defined efficacy criteria for clinically relevant activity and showed an acceptable safety profile in line with the TIGIT:PD-1 class. Clinically meaningful tumor reduction was observed at every belrestotug + dostarlimab dose vs dostarlimab monotherapy.

On June 17, 2024 Exicure reported its First Quarter 2024 Financial Results (Press release, Exicure, JUN 17, 2024, View Source [SID1234644728]).

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First Quarter 2024 Financial Results

Cash Position: Cash and cash equivalents were $0.4 million as of March 31, 2024, as compared to $0.8 million as of December 31, 2023. Subsequent to March 31, 2024, our cash and cash equivalents have decreased to approximately $0.2 million as of May 31, 2024. Subsequent to May 31, 2024, the Company received a $0.7 million loan from DGP Co., Ltd., a significant stockholder. The loan has a maturity of ten months from issuance and interest at a rate of 6.0% per annum is payable at maturity. The Company believes that its cash and cash equivalents are insufficient to continue to fund operations and additional funding is needed in the very near term.

Revenue: On February 5, 2024, the Company entered into a patent license agreement to develop cavrotolimod for potential treatment for hepatitis with a private clinical stage biopharmaceutical company. Under the terms of the agreement, this biopharmaceutical company will receive an exclusive license in the field of hepatitis to all of the Company’s relevant patents. An initial payment of $0.5 million was paid to the Company after the execution of this agreement. The Company will also be entitled to modest royalties on future net sales of all licensed technology during the term of the licensed patents.

Research and Development (R&D) Expense: Research and development expenses were $0 for the quarter ended March 31, 2024, as compared to $1.4 million for the quarter ended March 31, 2023. The decrease in R&D expense for the three months ended March 31, 2024 of $1.4 million reflects the stoppage of clinical, preclinical, and discovery program activities and a reduction in employee headcount with lower employee-related expenses and fewer discovery, preclinical, and clinical program activities resulting from the restructuring activities that the Company announced in December 2021 and September 2022.

General and Administrative (G&A) Expense: General and administrative expenses were $1.3 million for the quarter ended March 31, 2024, as compared to $3.1 million for the quarter ended March 31, 2023. The decrease in G&A expense of $1.8 million for the three months ended March 31, 2024 was mostly due to lower compensation and related payroll costs, professional fees, and operating costs as a result of reduced operations.

Net Loss: The Company had a net loss of $0.8 million for the quarter ended March 31, 2024, as compared to a net loss of $4.4 million for the quarter ended March 31, 2023. The decrease in net loss of $3.6 million was primarily driven by the reduction of payroll and operating costs due to reduced operations, as well as $0.5 million of revenue as a result of a license agreement payment received during the quarter.

Going Concern: Management believes that the Company’s existing cash and cash equivalents is not sufficient to continue to fund operations. The Company has already engaged in significant cost reductions, so our ability to further cut costs and extend the Company’s operating runway is limited. As a result, substantial additional financing is needed in very near term to pay expenses, fund the ongoing exploration of strategic alternatives and pursue any alternatives that may be identified. The Company needs to raise capital to fund its operations. There can be no assurance that such additional financing will be available and, if available, can be obtained on acceptable terms.

On June 17, 2024 Alivexis, Inc. (Headquartered in Minato-ku, Tokyo; CEO S. Roy Kimura) reported that the Company has entered into a Research Collaboration Agreement with Astellas Pharma Inc. ("Astellas") to identify small molecule compounds for a new drug target selected by Astellas, utilizing Alivexis’ drug discovery platform ModBind and other technologies (Press release, Alivexis, JUN 17, 2024, View Source [SID1234644376]).

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The collaboration aims to utilize Alivexis’ computational drug discovery platform, including ModBind, to discover new small molecule compounds which will regulate the function of a novel drug target molecule selected by Astellas. As this target has no reported functional modulators to-date, the collaboration will accelerate the drug discovery of novel therapeutics against the target. In addition to in silico evaluation using the computational drug discovery platform, Alivexis will be responsible for integrated drug discovery research, including the development of experimental assays and compound evaluation using those assays. Under the terms of the collaboration, Astellas will have the option to acquire rights to the research deliverables.

About ModBind.
Alivexis has established a computational drug discovery platform that greatly accelerates small molecule drug discovery, which includes physics-based molecular dynamics simulations using GPUs (Graphics Processing Units), large-scale virtual screening algorithms, and deep learning models. With the help of their computational drug discovery platform, Alivexis has already delivered several clinical candidate molecules for both in-house drug discovery projects and external collaborations. Among Alivexis’ various computational drug discovery tools, the newly developed ModBind is a molecular simulations-based algorithm that can predict the efficacy of drug candidate compounds with high accuracy, yet performs more than 100 times faster than the other state-of-the-art technologies in the field. ModBind is based on a theoretical approach that is fundamentally different from industry standard simulations-based prediction technologies. One significant advantage of ModBind is that it is an absolute predictor of ligand efficacy and does not require known reference compounds, which are usually necessary for other methodologies. Therefore, ModBind is useful in all stages of preclinical drug discovery – from screening large random chemical libraries for initial hit finding to delivering clinical candidates in the lead-optimization stage. This capability has already been proven by Alivexis’ in-house research and external collaborations and is contributing to the progression of many drug discovery projects.

【CEO S. Roy Kimura’s Comments】
"I am excited to announce the signing of our drug discovery collaboration with Astellas focused on the use of our proprietary and ground-breaking ModBind simulation technology to accelerate early drug discovery for a particular disease target. Through our collaboration, we look forward to gaining further validation of our technology while contributing to the discovery of novel clinical candidate compounds for diseases with high patient need."

On June 17, 2024 ReviR Therapeutics, a biotechnology company specializing in the development of small molecule RNA splicing modulators for neurogenetic diseases and oncology indications, and Asieris Pharmaceuticals, a global biopharmaceutical leader in the discovery, development, and commercialization of innovative drugs for genitourinary tumors and related diseases, reported that a milestone was reached in their ongoing collaboration (Press release, Asieris Pharmaceuticals, JUN 17, 2024, View Source [SID1234644402]). The joint effort to develop treatments for cancers using a novel target has resulted in the successful identification of a new lead series of small molecules that modulate the expression of an oncogenic driver gene. The molecules were discovered using ReviR’s proprietary VoyageR AI platform which has the potential to revolutionize therapeutic discovery across multiple indications, including genitourinary cancers.

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The collaboration successfully completed the first milestone of target engagement, and demonstrated that a series of molecules from ReviR’s proprietary compound library are capable of driving inclusion of a cryptic exon into the mRNA of a novel target gene, thus resulting in subsequent reduction of the disease protein. This discovery advances the development of a novel therapy for genitourinary cancers one step closer to clinical development. ReviR’s VoyageR AI platform offers significant advantages to characterize small molecule splicing modulators, including target identification as well as enhanced potency and specificity assessments across genomes. This platform holds immense promise for the development of novel treatments for a broad spectrum of genetic diseases including Huntington’s Disease, which is a key focus for ReviR’s pipeline development.

"We are very pleased with what our team, alongside our esteemed collaborators at ReviR Therapeutics, has accomplished. This milestone demonstrates the value of teamwork in accelerating advancements in drug discovery," said Alice Chen, Senior Vice President of Discovery Biology & Head of Translational Research at Asieris Pharmaceuticals.

Peng Yue, PhD, CEO of ReviR Therapeutics, said, "Today marks a significant milestone in our journey to develop a new therapy for cancers with limited treatment options. This breakthrough in splicing modulator technology brings us one step closer to bringing much-needed relief to patients."

Both companies are evaluating the option to further discover and develop novel small molecule splicing modulators towards novel targets and exploring the potential of expanding VoyageR to various therapeutic applications. This collaboration exemplifies the power of joint efforts in driving innovation within the field of splicing modulators and paving the way for a future with more effective treatments for genetic diseases and targeted oncology therapies.

On June 17, 2024 Aprea Therapeutics, Inc. (Nasdaq: APRE) ("Aprea", or the "Company"), a clinical-stage biopharmaceutical company focused on precision oncology through synthetic lethality, reported that the first patient has been dosed in the ACESOT-1051 Phase 1 study evaluating daily oral WEE1 inhibitor APR-1051 as monotherapy in advanced solid tumor patients with unmet medical need (Press release, Aprea, JUN 17, 2024, View Source [SID1234644378]).

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APR-1051 was discovered and preclinically evaluated by Aprea’s team of chemists and scientists. APR-1051 is a potent and highly selective small molecule designed to limit off-target toxicity that may provide good safety and tolerability and has shown a potentially favorable drug exposure in pre-clinical models.

APR-1051 targets WEE1 kinase, an enzyme involved in the DNA damage response pathway. Based on preclinical studies, we believe APR-1051 may solve liabilities associated with other WEE1 inhibitors and is differentiated based on: 1) molecular structure; 2) selectivity for WEE1 versus off-target inhibition of the polo-like kinase, or PLK, family of kinases; 3) potentially improved pharmacokinetic (PK) properties; and 4) potential absence of QT prolongation at doses that significantly inhibit WEE1. No head-to-head studies with APR-1051 have been conducted.

ACESOT-1051 is a focused biomarker-driven study with advanced/metastatic solid tumors harboring the following cancer-associated gene alterations:

Amplification/overexpression of CCNE1 or CCNE2 regardless of tumor type, or
Deleterious mutations in FBXW7 or PPP2R1A regardless of tumor type, or
Colorectal cancer with KRAS-GLY12 and TP53 co-mutation, or
Uterine serous carcinoma regardless of biomarker status
"Dosing of the first patient in the ACESOT-1051 study is an important milestone in our APR-1051 development program and represents a key advancement of our clinical pipeline," said Oren Gilad, Ph.D., President and Chief Executive Officer of Aprea. "Adding a second clinical program enriches our asset portfolio. We are initially evaluating single agent activity of APR-1051 to provide the basis for future rational combination treatments. We hope to confirm APR-1051’s safety profile in this Phase 1 study and generate the necessary data that will help us understand how it can be best utilized to treat patients. We plan to provide a clinical update by year-end 2024 and generate preliminary efficacy data during 2025."

The first patient was enrolled at NEXT Oncology, San Antonio, Texas. Additional centers, including The University of Texas MD Anderson Cancer Center, are expected to participate.

Anthony Tolcher M.D., Founder of Next Oncology commented, "NEXT Oncology is committed to exploring new treatment options for cancer patients and we are pleased to begin this important clinical trial. Cancers that over express Cyclin E (CCNE1 and CCNE2) represent a high unmet medical need, and patients with Cyclin E over expression have poor prognosis and no effective therapies. WEE1 kinase is a validated oncology target and we look forward to the results of this study."

ACESOT-1051 Study Design

ACESOT-1051 (A Multi-Center Evaluation of WEE1 Inhibitor in Patients with Advanced Solid Tumors, APR-1051) is designed to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of single-agent APR-1051 in advanced solid tumors harboring cancer-associated gene alterations. Oral APR-1051 will be administered once daily for 28-day cycles. The study consists of two parts: Part 1 is dose escalation and is expected to enroll up to 39 patients with advanced solid tumors. The first three dose levels will use accelerated titration followed by Bayesian Optimal Interval (BOIN) design for the remaining dose levels; Part 2 (up to 40 patients) is designed for dose optimization, with the goal of selecting the Recommended Phase 2 Dose (RP2D).

The primary objectives of the study are to measure safety, dose-limiting toxicities (DLTs), maximum tolerated dose or maximum administered dose (MTD/MAD), and RP2D; secondary objectives are to evaluate pharmacokinetics, preliminary efficacy according to RECIST or PCWG3 criteria; pharmacodynamics is an exploratory objective. The University of Texas MD Anderson Cancer Center is the lead site, and the study will be performed at between 3 and 10 sites in the U.S.

The ACESOT-1051 design was featured in a poster at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) annual meeting which took place in April 2024 in San Diego. A copy of the poster can be found here. For more information, refer to ClinicalTrials.gov NCT06260514.