RORG

Data demonstrated soquelitinib was active in six inflammatory/immune disease models and provides rationale for development in a range of additional Th2- and Th17-mediated diseases Soquelitinib’s unique mechanism of action inhibited the production of Th2 and Th17 cells, providing upstream attenuation of several validated cytokine targets such as IL-4, IL-5, IL-13, IL-17 BURLINGAME, Calif., Nov. 01, 2023 (GLOBE NEWSWIRE) -- Corvus Pharmaceuticals, Inc. (Nasdaq: CRVS), a clinical-stage biopharmaceutical company, today announced the publication of preclinical data that demonstrated the potential of ITK inhibition as a novel approach to treat T cell-mediated inflammatory and immune diseases. Corvus’ ITK inhibitors include soquelitinib (formerly known as CPI-818), which was used in the preclinical studies and is currently in clinical trials for oncology indications, and several next-generation molecules that are being optimized for use in a variety of inflammatory and immune disease indications. “Our research on soquelitinib and selective ITK inhibition is uncovering valuable new information about immune function and the role of ITK in different diseases,” said James Rosenbaum, M.D., senior vice president of research at Corvus. “The activity of soquelitinib in various inflammatory and immune disease models highlights the essential role of ITK in multiple T cell functions. Our publication demonstrates that soquelitinib can impact disease-associated cytokines by targeting the cellular sources, specifically Th2 and Th17 cells, which produce cytokines like IL-4, IL-5, IL-13 and IL-17. We believe that blocking the source of cytokine production upstream offers advantages over existing therapies that individually target specific cytokines.” Professor Yannick Allanore, M.D., Ph.D., Professor of Rheumatology, Université Paris Cité, Institut Cochin, Paris, France, and a co-author of the publication, said, “Pulmonary fibrosis and systemic sclerosis are often fatal diseases for which current therapy is inadequate. Soquelitinib utilizes a novel mechanism and was effective in our model related to systemic sclerosis which is based on Fra2 gene overexpression, a model designed to represent human lung disease manifestations. Based on these data, we are eager to evaluate soquelitinib in a clinical trial for fibrotic diseases.” The publication, entitled “Soquelitinib, A Selective Inhibitor of Interleukin- 2- Inducible T Cell Kinase (ITK), is Active in Several Murine Models of T Cell-Mediated Inflammatory Disease,” highlights data demonstrating that soquelitinib was active in six different models of T cell-mediated inflammatory and immune disease, including acute and chronic asthma, pulmonary fibrosis, systemic sclerosis (scleroderma), psoriasis, and acute graft versus host disease. The data also describe soquelitinib’s unique mechanism of action, providing rationale for the development of ITK inhibition in a range of additional Th2 and Th17 mediated diseases, including asthma, psoriasis, atopic dermatitis, chronic obstructive pulmonary disease (COPD), systemic sclerosis, lupus and other diseases. The published research was a result of collaborations between scientists at Corvus and researchers at both Memorial Sloan Kettering Cancer Center in New York and The National Institute of Health and Medical Research (INSERM) in France. The publication is now available online as a preprint at bioRxiv.org and on the Publications and Presentations page of the Corvus website. “We are making significant progress with soquelitinib and believe that Corvus is firmly positioned as a leader in the scientific and clinical development of ITK inhibition as a platform opportunity across cancer, inflammation and immune disease,” said Richard A. Miller, M.D., co-founder, president, and CEO of Corvus. “Our primary focus is treating T cell lymphomas and cancer and we are actively preparing for a registrational Phase 3 trial of soquelitinib for peripheral T cell lymphoma. With this new publication, we further demonstrate the wide range of opportunities for ITK inhibition across specific indications with ongoing patient needs for new therapies. In addition, we have a robust pipeline of next generation ITK inhibitors and a portfolio of intellectual property that we believe provide attractive partnering opportunities for companies focused on various inflammatory and immune diseases.” Key results from the preclinical studies described in the publication demonstrated that soquelitinib had the following observed effects in models of inflammatory disease: Acute and chronic asthma models: Significant reductions in Th2 cytokines IL-4, IL-5 and IL-13 in both models, along with reductions in a validated disease activity scoreReduction in IL-6 signifying amelioration of inflammation Systemic sclerosis (Fra2 gene overexpression) model: Improvement in clinical score and preservation of body weightImprovement in lung histology, reduction of fibrosis and improvement in pulmonary vascular hypertensionReduction of GATA3-expressing T cells, indicative of effect on Th2 cellsReduction of ROR gammaT cells (RORγT), indicative of effects on Th17 cells Pulmonary fibrosis (bleomycin-induced) model: More consistent reduction of pulmonary fibrosis compared to an FDA-approved medication (nintedanib)Similar reduction in GATA3 as the systemic sclerosis model resultsReduction in MMP2 and TGF beta, two messenger RNAs associated with fibrosis Psoriasis (imiquimod (IMQ)-induced) model: Improvement in epidermal thickness, erosion and inflammationIn vitro studies demonstrated a reduction in the expression of RORγT protein, a master transcription factor that is responsible for developing Th17 cells, and a corresponding dose-dependent reduction in IL-17 cytokine production Graft versus host disease (GVHD) model: Improvement in survival rates and corresponding decrease in clinical GVHD scoreNo impact on engraftment or graft-versus-tumor effect About Corvus PharmaceuticalsCorvus Pharmaceuticals is a clinical-stage biopharmaceutical company pioneering the development of ITK inhibition as a new approach to immunotherapy for a broad range of cancer and immune diseases. The Company’s lead product candidate is soquelitinib, an investigational, oral, small molecule drug that selectively inhibits ITK. Corvus plans to initiate a Phase 3 registrational clinical trial for soquelitinib in patients with relapsed peripheral T cell lymphoma. Its other clinical-stage candidates are being developed for a variety of cancer indications. For more information, visit www.corvuspharma.com. About SoquelitinibSoquelitinib (CPI-818) is an investigational small molecule drug given orally designed to selectively inhibit ITK (interleukin-2-inducible T cell kinase), an enzyme that is expressed predominantly in T cells and plays a role in T cell and natural killer (NK) cell immune function. The immunologic effects of soquelitinib lead to what is known as Th1 skewing and is made possible by the high selectivity of soquelitinib for ITK. Research on soquelitinib’s mechanism of action suggests that it has the potential to control differentiation of normal T helper cells and enhance immune responses to tumors by augmenting the generation of cytotoxic killer T cells and the production of cytokines that inhibit cancer cell survival. Soquelitinib has also been shown to prevent T cell exhaustion, a major limitation of current immunotherapy and CAR-T therapies. Optimal doses of soquelitinib have been shown to affect T cell differentiation and induce the generation of Th1 helper cells while blocking the development of both Th2 and Th17 cells and production of their secreted cytokines. Th1 T cells are required for immunity to tumors, viral infections and other infectious diseases. Th2 and Th17 helper T cells are involved in the pathogenesis of many autoimmune and allergic diseases. The Company believes the inhibition of specific molecular targets in T cells may be of therapeutic benefit for patients with cancers, including solid tumors, and in patients with autoimmune and allergic diseases. Based on interim results from a Phase 1/1b clinical trial in patients with refractory T cell lymphomas, which demonstrated tumor responses in very advanced, refractory, difficult to treat T cell malignancies, the Company plans to initiate a registrational Phase 3 clinical trial of soquelitinib in patients with relapsed peripheral T cell lymphoma (PTCL). Forward-Looking StatementsThis press release contains forward-looking statements, including statements related to the potential safety and efficacy of the Company’s product candidates including soquelitinib, ciforadenant and mupadolimab; the potential use of soquelitinib to treat a variety of solid tumors and hematological cancers; the Company’s ability and its partners’ ability, as well as the timing thereof, to develop and advance product candidates through and successfully complete preclinical studies and clinical trials; the timing of and the Company’s ability to launch clinical trials including the potential registrational Phase 3 clinical trial for soquelitinib; and whether the Company is able to secure any partnerships or advance soquelitinib in any other indications. All statements other than statements of historical fact contained in this press release are forward-looking statements. These statements often include words such as “believe,” “expect,” “anticipate,” “intend,” “plan,” “estimate,” “seek,” “will,” “may” or similar expressions. Forward-looking statements are subject to a number of risks and uncertainties, many of which involve factors or circumstances that are beyond the Company’s control. The Company’s actual results could differ materially from those stated or implied in forward-looking statements due to a number of factors, including but not limited to, risks detailed in the Company’s Quarterly Report on Form 10-Q for the three months ended June 30, 2023, filed with the Securities and Exchange Commission on August 8, 2023, as well as other documents that may be filed by the Company from time to time with the Securities and Exchange Commission. In particular, the following factors, among others, could cause results to differ materially from those expressed or implied by such forward-looking statements: the Company’s ability to demonstrate sufficient evidence of efficacy and safety in its clinical trials of soquelitinib and its other product candidates; the accuracy of the Company’s estimates relating to its ability to initiate and/or complete preclinical studies and clinical trials and release data from such studies and clinical trials; the results of preclinical studies and interim data from clinical trials not being predictive of future results; the Company’s ability to enroll a sufficient number of patients in its clinical trials; the unpredictability of the regulatory process; regulatory developments in the United States, and other foreign countries; the costs of clinical trials may exceed expectations; and the Company’s ability to raise additional capital. Although the Company believes that the expectations reflected in the forward-looking statements are reasonable, it cannot guarantee that the events and circumstances reflected in the forward-looking statements will be achieved or occur, and the timing of events and circumstances and actual results could differ materially from those projected in the forward-looking statements. Accordingly, you should not place undue reliance on these forward-looking statements. All such statements speak only as of the date made, and the Company undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise. INVESTOR CONTACT:Leiv LeaChief Financial OfficerCorvus Pharmaceuticals, Inc.+1-650-900-4522llea@corvuspharma.com MEDIA CONTACT:Sheryl SeapyReal Chemistry+1-949-903-4750sseapy@realchemistry.com

Phosphorus is a natural mineral found in fertilizer that is essential for plant growth and development, and Earth's agricultural-grade phosphorus reserves are expected to be depleted in 50 to 100 years. A new discovery is changing their understanding of iron toxicity in plants caused by low phosphorus levels. Phosphorus is a natural mineral that is essential for plant growth and development, and Earth's agricultural-grade phosphorus reserves are expected to be depleted in 50 to 100 years. A new discovery by researchers at Michigan State University and the Carnegie Institution for Science is changing their understanding of iron toxicity in plants caused by low phosphorus levels. "Once the world's supply is used up, we can't make more phosphorus," said Hatem Rouached, an assistant professor in MSU's College of Agriculture and Natural Resources and a member of the Plant Resilience Institute. "Ideally, we would like to be able to use less phosphorus in the soil to grow plants." Plants absorb phosphorus from the soil. When soil doesn't contain enough phosphorus, plants will take up more iron from the soil, which becomes toxic at increased levels. Previous research supported the idea that iron toxicity caused a plant's roots to stop growing. Now, for the first time, researchers at MSU and the Carnegie Institution for Science have found evidence that the plant roots stop growing early, without any evidence of iron. This changes the way researchers look at this problem. "If iron toxicity is the cause, then why does the root stop growing before iron accumulates in the roots?" said Seung Yon "Sue" Rhee, incoming director of MSU's Plant Resilience Institute in the College of Natural Science and an MSU Research Foundation Professor, currently at the Carnegie Institution for Science. "We knew there must be something else happening." Using computational models to build gene regulatory networks, Rouached, Rhee and their team isolated a specific gene called an Arabidopsis root-specific kinase 1 that regulates the target of rapamycin, or TOR, complex, which is the key developmental regulator in plants, fungi and animals. When a plant is starved of phosphorus, the gene downregulates the TOR complex, which sends a signal to the root of the plant to stop growing. "This is the first time anyone has linked a phosphorus deficiency signal to a TOR kinase in vascular plants," said Rhee. The researchers have filed a patent on this process and plan to explore other applications of this gene. "We believe that this is a game changer in the field of plant mineral nutrition," said Rouached. "We want to engineer plants whose roots will continue to grow despite phosphorus limitation." The research was published in the journal Current Biology.

LANCASTER, Calif.--( BUSINESS WIRE )-- Simulations Plus, Inc. (Nasdaq: SLP), a leading provider of modeling and simulation software and services for pharmaceutical safety and efficacy, today announced that it entered into a collaborative research agreement with the Institute of Medical Biology of the Polish Academy of Sciences (IMB PAS) to jointly design new compounds for the RORγ/RORγT nuclear receptors using its cutting-edge artificial intelligence (AI) / machine learning (ML) technology in the ADMET Predictor® software platform. Per the terms of the collaboration, Simulations Plus will deploy the AIDD Module in ADMET Predictor® to create predictive models of inhibition and activation for the human RORγ/RORγT nuclear receptors. The computational and medicinal chemists at Simulations Plus will then interact with researchers at the IMB PAS to define the multi-objective parameters against which the lead molecule(s) will be optimized. The generative chemistry approaches within the AIDD Module will produce novel libraries of virtual compounds with desired combinations of the properties chosen, and the IMB PAS will synthesize and test promising analogs. Emerging intellectual property, in the form of encouraging lead compounds, will be jointly owned by Simulations Plus and IMB PAS for further development opportunities. “Many organizations continue to explore the use of AI algorithms to complement the drug design and lead optimization process with human interaction,” said Dr. Rafal Bachorz , Senior Cheminformatics Scientist II at Simulations Plus and project lead. “We are excited to work with the IMB PAS to apply our cheminformatic toolkits with the AIDD Module to generate novel chemical matter for the human RORγ/RORγT nuclear receptors.” “Simulations Plus is an organization that has the AI-based drug discovery technology and computational/medicinal chemistry skills which are unique in a partner,” added Professor Jarosław Dziadek, director of the IMB PAS. “Our goal is to combine our expertise with RORγ/RORγT receptor biology, which many pharmaceutical companies are targeting as it may be involved in the progression of certain types of cancer, and relevant assays of receptor activity with all that Simulations Plus offers to accelerate the design and optimization of novel lead molecules.” John DiBella , SLP Division President, said: “This collaboration is another in a long line of ‘win-win’ situations, although this time with a twist. Both Simulations Plus and the IMB PAS will be making meaningful contributions in areas where each organization is strongest, and we will share equally the promising outcomes which are generated. We are highly motivated to explore where this will take us in terms of identifying the next generation of compounds that could help in the treatment of cancer. Simulations Plus continues to invite future collaborations which benefit organizations and, most importantly, the global communities we serve.” About Simulations Plus, Inc. Serving clients worldwide for more than 25 years, Simulations Plus is a leading provider in the biosimulation market providing software and consulting services supporting drug discovery, development, research, and regulatory submissions. We offer solutions that bridge machine learning, physiologically based pharmacokinetics, quantitative systems pharmacology/toxicology, and population PK/PD modeling approaches. Our technology is licensed and applied by major pharmaceutical, biotechnology, and regulatory agencies worldwide. For more information, visit our website at www.simulations-plus.com . Follow us on LinkedIn | Twitter | YouTube . About the Institute of Medical Biology at the Polish Academy of Sciences Established in 1951, the Polish Academy of Sciences is a Polish state-sponsored institution of higher learning. Headquartered in Warsaw, it is responsible for spearheading the development of science across the country by a society of distinguished scholars and a network of 68 research institutes. Safe Harbor Statement Under the Private Securities Litigation Reform Act of 1995 – With the exception of historical information, the matters discussed in this press release are forward-looking statements that involve a number of risks and uncertainties. Words like “believe,” “expect” and “anticipate” mean that these are our best estimates as of this writing, but that there can be no assurances that expected or anticipated results or events will actually take place, so our actual future results could differ significantly from those statements. Factors that could cause or contribute to such differences include, but are not limited to: our ability to maintain our competitive advantages, acceptance of new software and improved versions of our existing software by our customers, the general economics of the pharmaceutical industry, our ability to finance growth, our ability to continue to attract and retain highly qualified technical staff, our ability to identify and close acquisitions on terms favorable to the Company, and a sustainable market. Further information on our risk factors is contained in our quarterly and annual reports and filed with the U.S. Securities and Exchange Commission.