PRF1

Data presented at the Society for Immunotherapy of Cancer (SITC) 38th Annual Meeting Longitudinal comparison of biomarkers in tumor microenvironment showed a gradual, durable response over time in T lymphotactic CXCR3 ligands and cytolytic factors Phase 2 study ongoing; topline interim results expected before year end AIM ImmunoTech Inc. (NYSE American: AIM) (“AIM”), an immuno-pharma company focused on the research and development of therapeutics to treat multiple types of cancers, immune disorders and viral diseases, today announced encouraging translational data from an ongoing Phase 2 clinical trial utilizing AIM’s drug Ampligen® in patients with platinum-sensitive advanced recurrent ovarian cancer. The abstract with data illustrations, titled “Combination intraperitoneal chemoimmunotherapy triggers a T-cell chemotactic locoregional response in patients with recurrent platinum-sensitive ovarian cancer,” was presented by collaborators from the Magee-Womens Research Institute at the University of Pittsburgh School of Medicine (“UPMC") — one of the world’s top centers for the treatment of gynecological cancers — at the recent Society for Immunotherapy of Cancer (SITC) 38th Annual Meeting, in San Diego, Calif. The data was also made available at the conference in a poster presentation. Data highlighted in the abstract were collected by UPMC through translational studies focused on the immune tumor microenvironment (TME), using a longitudinal collection of biospecimens, including plasma, PBMC, IP washes and tumor tissue collected from patients treated in a Phase 2, efficacy/safety trial (NCT03734692) combining intraperitoneal (IP) chemotherapy (cisplatin) with dual agent immunotherapy using intravenous (IV) pembrolizumab (anti-PD1, Keytruda®, provided by Merck) and IP rintatolimod (Ampligen®, a dsRNA acting as toll-like receptor 3 -TLR-3- agonist, provided by AIM). Sequential sampling of the IP cavity showed an increase in cellularity immediately after treatment consistent with an “acute” pro-inflammatory reaction. Mesoscale Delivery (MSD) measurements in IP washes revealed an acute increase in granzyme B, perforin, TNF alpha, CXCL9, CXCL10, and CXCL11 after treatment (p<0.05). Longitudinal data revealed a progressive increase in some biomarkers (p<0.05). RNA sequencing data showed a significant upregulation acutely in STAT1 and downstream targets, CXCL9, 10, 11 and TH1 type response genes (p<0.05). Robert P. Edwards, MD, Chief Medical Officer of the UPMC Community and Ambulatory Services Division and Co-Director of the Women’s Cancer Research Center at the UPMC Hillman Cancer Center, stated, “The profound local T-cell cytoxicity activation we see with this combination is markedly improved over previous work we have published on this platform with this recurrent disease profile.” David Strayer, MD, AIM’s Medical Officer, a Board-Certified oncologist and a former Professor of Medicine and Neoplastic Diseases at Hahnemann University, stated, “We continue to be encouraged by the data being demonstrated by Dr. Robert Edwards and his team at UPMC. These data highlight the effectiveness of combinatorial treatments including Ampligen in modulating the cellular make-up of the tumor microenvironment through cytokine profile changes. These data show a similar profile to previously published data from Roswell Park in Stage 4 triple negative breast cancer. The thing that intrigues me most is the persistent upregulation of the T-lymphotactic cytokines over time, and the lack of immune exhaustion as demonstrated in the ability of the treatment to cause a statistically significant upregulation of these cytokines after repeated treatment. As a whole, these data demonstrate an encouraging result in the promotion of increased T cell chemotaxis and cytolytic function for improved clinical outcomes in patients with advanced recurrent ovarian cancer.” AIM Chief Executive Officer Thomas K. Equels stated, “There is a significant unmet need in advanced recurrent ovarian cancer and these findings continue to bolster our confidence in Ampligen’s potential. Additionally, we hope to announce topline interim survival results from UPMC in the near future.” For more information about the Phase 2 clinical trial of platinum-sensitive advanced recurrent ovarian cancer utilizing Ampligen®, visit clinicaltrials.gov and reference identifier: NCT03734692. AIM ImmunoTech Inc. is an immuno-pharma company focused on the research and development of therapeutics to treat multiple types of cancers, immune disorders and viral diseases, including COVID-19. The company’s lead product is a first-in-class investigational drug called Ampligen® (rintatolimod), a dsRNA and highly selective TLR3 agonist immuno-modulator with broad spectrum activity in clinical trials for globally important cancers, viral diseases and disorders of the immune system. The content above comes from the network. if any infringement, please contact us to modify.

— AB821, a highly differentiated CD8-targeted interleukin-21 (IL-21) immunotherapy, demonstrates potent preclinical antitumor activity — — On track to investigational new drug (IND) application for AB821 in 4Q 2023 — SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Asher Biotherapeutics, a biotechnology company developing precisely-targeted immunotherapies for cancer, autoimmune, and infectious diseases, today announced new preclinical data for AB821, its CD8-targeted interleukin-21 (IL-21) immunotherapy. The data will be presented at the Society for Immunotherapy in Cancer (SITC) 38th Annual Meeting, being held in San Diego, CA on November 1-5, 2023. “We are pleased to share new preclinical data for AB821 at SITC, further illustrating the potential of our highly differentiated cis-targeted immunotherapies for the treatment of cancer,” said Andy Yeung, Ph.D., Chief Technology Officer and Co-founder of Asher Bio. “IL-21 has historically demonstrated promising antitumor activity, but its clinical use has been limited due to toxicities and pleiotropic effects. We designed AB821 to activate only CD8+ T cells, the immune cell type driving the antitumor response, potentially maximizing the efficacy of IL-21 and limiting off-target activity. The new preclinical data presented at SITC demonstrate that AB821 can improve the functionality of exhausted CD8+ T cells and promote their function and survival to effectively facilitate potent antitumor activity. Based on these data, we believe AB821 could significantly improve the treatment paradigm for patients with tumor types unresponsive to checkpoint blockade therapies, who typically have highly exhausted CD8+ T cells in their tumors. We look forward to advancing AB821’s clinical development and remain on track to IND in the fourth quarter of 2023.” New Preclinical Data for AB821, Asher Bio’s CD8-Targeted IL-21 In a poster presentation entitled, “AB821 is a CD8+ T cell selective IL-21 with enhanced bioavailability that reduces CD8+ T cell exhaustion to induce potent antitumor activity,” lead author Renee Greer, Ph.D., Principal Scientist at Asher Bio, described new preclinical data further characterizing the mechanisms by which AB821 enhances the functionality of CD8+ T cells and facilitates the antitumor effects of IL-21, further supporting AB821’s development. The data show: A murine surrogate of AB821 (muAB821) demonstrated potent antitumor activity both as a monotherapy and in combination with anti-PD-1 therapy in anti-PD-1 refractory mouse tumor models. Exhausted CD8+ T cells are a promising target for AB821 therapy, as supported by the following: High levels of IL-21R were observed in the exhausted CD8+ T cell subset in mouse tumors and in human tumor-infiltrating lymphocytes (TILs) Treatment with muAB821 resulted in replacement of exhausted CD8+ T cells with CD8+ T cells with restored cytotoxic potential and expressing memory markers. In human TILs, exhausted CD8+ T cells were shown to be highly responsive to treatment with AB821 as measured by pSTAT3 sensitivity. In human TILs cultured with AB821, AB821 acted on exhausted CD8+ T cells to improve their antitumor functionality by increasing expression and secretion of key effector proteins such as Granzyme B and perforin, both of which are essential for antitumor activity. Clinical Trial in Progress for AB248, Asher Bio’s CD8-Targeted IL-2 Also at SITC, a poster highlighting Asher Bio’s lead immunotherapy candidate, AB248, a CD8+ T cell-selective IL-2, will be featured in a clinical trial in progress poster. The poster, entitled “An open-label, Phase 1a/b study of AB248, a CD8+ T selective IL-2 mutein fusion protein, alone or in combination with pembrolizumab in patients with advanced solid tumors,” details the design of the ongoing Phase 1a/1b study of AB248 alone and in combination with pembrolizumab in patients with advanced solid tumors who failed prior standard of care treatments (NCT05653882). Asher Bio initiated this Phase 1a/1b study in January 2023. Both poster presentations will be available in the “Presentations and Posters” section of Asher Bio’s website: . About AB821 IL-21 is a cytokine that activates STAT3, a master transcription factor involved in a broad spectrum of adaptive and innate immune functions. In oncology, IL-21 has historically demonstrated promising in early clinical studies, but was hindered by toxicities and pleiotropic effects, such as suppression of antigen presentation, which could dampen overall antitumor efficacy. Asher Bio hypothesized that focusing the activity of IL-21 to only the immune cell type primarily responsible for antitumor efficacy, while avoiding activation of other cells, would maximize the efficacy potential of IL-21 and reduce toxicity. Like IL-2, IL-21 derives its benefit from stimulating CD8+ T cells, but it mediates antitumor activity via a distinct, potentially complementary pathway. Asher Bio developed AB821 as a cis-targeted IL-21 activating cytokine that selectively targets CD8+ T cells, the immune cell type driving antitumor response. The IL-21 activating cytokine promotes cytotoxicity, memory cell differentiation, survival and reinvigoration of CD8+ T cells, all of which support antitumor activity. Asher Bio believes that AB821 has the potential to treat tumor types that may not be responsive to IL-2 and/or PD-1 therapy. PD-1-resistant tumors are associated with reduced memory T cell numbers and increased exhausted T cell numbers, suggesting that this molecule may be beneficial in these resistant tumors. AB821 also has the potential to be used in combination with AB248 to enhance efficacy by combining a proliferation signal with one that optimizes functionality and prevents T cell exhaustion. About Asher Bio Asher Bio is a biotechnology company developing therapies to precisely engage specific immune cells to fight cancer, chronic viral infection and autoimmune disease. We utilize our proprietary cis-targeting platform to develop therapies engineered to overcome limitations of other immune-based treatments by selectively activating specific immune cell types with validated disease fighting functionality. Our candidates feature an antibody connected to a modified immunomodulatory protein, such as a cytokine. Our candidate design is intended to enable our candidates to selectively activate the desired immune cells and not other cells that contribute to toxicity or immune suppression. Our lead program AB248, an IL-2 molecule specifically targeted to CD8+ effector T cells, is currently in Phase 1 trials for oncology. Asher Bio was founded by Ivana Djuretic and Andy Yeung with support from Third Rock Ventures and is located in South San Francisco. For more information, please visit and follow us on X (formerly Twitter) @AsherBio and on LinkedIn.

Data supported CPI-818’s novel immunotherapy mechanism of action and its potential to provide a platform approach to a broad range of solid and hematological cancers Laboratory and clinical data demonstrated induction of host Th1 immune response that is independent of checkpoint inhibition Company plans to meet with FDA during 3Q23 to discuss the design of a potential registrational Phase 3 randomized clinical trial of CPI-818 in patients with T cell lymphoma BURLINGAME, Calif., June 15, 2023 (GLOBE NEWSWIRE) -- Corvus Pharmaceuticals, Inc. (Nasdaq: CRVS), a clinical-stage biopharmaceutical company, today announced new data for CPI-818, the Company’s ITK inhibitor, demonstrating the potential to treat a variety of solid and hematological cancers based on a novel immunotherapy mechanism of action. The data includes updated interim results from the CPI-818 Phase 1/1b clinical trial that continues to demonstrate the potential of ITK inhibition and the absolute lymphocyte count (ALC) biomarker in T cell lymphoma (TCL). The data is being presented in a poster at the International Conference on Malignant Lymphoma (ICML) meeting, which is taking place June 13-17, 2023 in Lugano, Switzerland. “The CPI-818 data presented at the ICML meeting demonstrates the potential of ITK inhibition to provide a novel immunotherapy mechanism of action for cancer therapy,” said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. “The preclinical and clinical data indicate a consistent and comprehensive rationale based on the biology and mechanism of immune enhancement resulting from selective ITK inhibition. This includes the ability to modulate normal T cell differentiation to enhance and strengthen the immune system’s ability to treat lymphomas and solid tumors. We see this in the interim tumor response data, which showed that a majority of the patients treated with the optimal dose of 200mg twice per day of CPI-818 experience tumor regression. As we consider the landscape of cancer therapy targets, ITK is not in the category of immune checkpoints, but rather it is a kinase that controls whether T cells become cancer killing cells or inflammatory cells. This positioning and the supporting research provide a strong foundation for the continued development of CPI-818 as a monotherapy and its future use in combinations with other therapies. We are excited to build upon these results and plan to meet with the U.S. FDA in the third quarter 2023 to discuss a potential registrational Phase 3 clinical trial for CPI-818 in T cell lymphoma. We also have begun planning for clinical trials with CPI-818 monotherapy in solid tumors. Overall, we have increasing confidence that CPI-818, if approved, can be a novel backbone for various immunotherapies of cancer.” CPI-818 Data Presented at ICMLThe CPI-818 preclinical and clinical data was presented by Ning Ding, Ph.D. from Peking University Cancer Hospital & Institute in Beijing, China, in a poster session (abstract #193) today at the ICML meeting. The poster is available to ICML attendees in the poster hall and e-poster gallery, is also available on the Publications and Presentations page of the Corvus website. The key highlights from the poster presentation include: Phase 1/1b Clinical Trial Interim DataCPI-818 is currently being studied in a Phase 1/1b clinical trial as a single agent therapy in patients with relapsed TCL. Corvus recently incorporated a minimum ALC as an eligibility criterion for enrollment in the clinical trial. Based on the current enrollment rate of the Phase 1/1b clinical trial, Corvus believes that the number of patients treated in this clinical trial would provide adequate safety and preliminary efficacy data to inform the design of a potential registrational Phase 3 randomized clinical trial. As recommended by the FDA, Corvus plans to meet with the FDA to discuss such a clinical trial; it is anticipated that this meeting will take place during the third quarter of this year. Updated interim data as of May 18, 2023 (waterfall plot shown below): A total of 30 patients were enrolled in the Phase 1/1b trial at the optimum 200 mg two-times a day dose, including 20 evaluable for tumor response. There were 3 complete responses (CR) and 3 partial responses (PR) with one of these PRs demonstrating continued regression of the tumor. One of the patients with a CR and 2 with PRs remained on therapy. A total of ten patients remained on therapy, including six who have not had their initial tumor response evaluation. For patients with ALC above 900 per cubic milliliter of blood, objective responses (CR plus PR) were seen in 6 of 14 patients with disease control (CR, PR and stable disease) in 12 of 14 patients. No objective responses were seen in six patients (0 for 6) with ALC below 900.Updated interim data as of May 18, 2023: In one TCL patient treated with CPI-818 for which serial tumor biopsy samples could readily be obtained, single cell RNA sequencing from paired samples comparing baseline and on-treatment specimens showed an increase in tumor infiltrating CD8+ T cells; an increase in cytolytic effector molecules such as granzymes and perforin in the T cells; and an increase in T effector memory cells (TEMRA cells), which are T cells that have responded to an antigen and are able to mediate effector functions, such as the destruction of tumor cells. In addition, flow cytometry analysis of paired blood samples comparing baseline and on treatment revealed a similar finding in both CD8 T cells and CD4 T cells. These results are consistent with preclinical data described below and support the novel immunotherapy mechanism of action of selective ITK inhibition, which is based on Th1 skewing and the resulting shift in immune response to eliminating cancer cells. Additional laboratory findings indicated that treatment with CPI-818 induces a reversal of T cells expressing exhaustion markers. T cell exhaustion is a known mechanism of resistance to checkpoint inhibitor therapy. Figure 1: Waterfall Plot for Patients in the 200 mg Dose Cohort of the CPI-818 Phase 1/1b Clinical Trial for T Cell Lymphoma. The plot shows the best percent change in tumor volume in the 18 patients (out of 20 total evaluable patients) that were measurable by CT scan. The two other patients had cutaneous and blood involvement; one was a patient with a PR and one patient had progression. Preclinical Data Supporting CPI-818’s Novel Immunotherapy Mechanism of ActionITK inhibition with CPI-818 has the potential to treat solid and hematological cancers through a novel mechanism of action that has demonstrated the ability to modulate T cell differentiation and enhance the anti-tumor immune response via Th1 skewing, increased T cell cytolytic capacity and reduction of T cell exhaustion. CPI-818 monotherapy provided statistically significant inhibition of tumor growth in established tumors in the following cancer models: EL4 TCL, A20 B cell lymphoma and CT26 colon cancer.In the EL4 TCL model, treatment with CPI-818 led to increased infiltration of normal CD8+ T cells into the tumor. In addition, these CD8+ T cells had higher expression of perforin, an effector molecule produced by killer T cells that is involved in killing cancer cells.In the CT26 colon cancer model, the depletion of CD8 cells reduced the efficacy of CPI-818 treatment, indicating that its mechanism of action involves the production of normal CD8+ T cells.In the CT26 colon cancer model, treatment with CPI-818 reduced the expression of T cell exhaustion markers. T cell exhaustion is a phenomenon seen in tumors and chronic infections where prolonged exposure to antigens results in exhausted or ineffective T cell function and inability to eliminate tumors or infections.In other murine studies using antigen primed T cells that were repeatedly stimulated, CPI-818 reduced the development of T cell exhaustion and reversed it in already exhausted T cells. These reinvigorated T cells regained their cancer cell killing capacity.These findings indicate that the inhibition of ITK by CPI-818 produces changes in the tumor microenvironment that enhance anti-tumor immunity creating a less favorable environment for tumor growth. 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 CPI-818, an investigational, oral, small molecule drug that selectively inhibits ITK and is in a mid-stage clinical trial for patients with 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 CPI-818CPI-818 is an investigational small molecule drug given orally that has selectively inhibited ITK (interleukin-2-inducible T cell kinase) in preclinical studies. ITK, an enzyme, is expressed predominantly in T cells and plays a role in T cell and natural killer (NK) cell immune function. The immunologic effects of CPI-818 lead to what is known as Th1 skewing and is made possible by the high selectivity of CPI-818 for ITK. Recent clinical data in T cell lymphomas, and preclinical studies in murine solid tumor models, suggests that CPI-818 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. Optimal doses of CPI-818 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 Th2 related 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. The Company is conducting a Phase 1/1b trial in patients with refractory T cell lymphomas that was designed to select the optimal dose of CPI-818 and evaluate its safety, PK, target occupancy, immunologic effects, biomarkers and efficacy. Interim data from the Phase 1/1b clinical trial of CPI-818 for T cell lymphoma demonstrated tumor responses in very advanced, refractory, difficult to treat T cell malignancies, and identified a dose that maximally drives Th1 skewing. 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 CPI-818; the potential use of CPI-818 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 into and successfully complete preclinical studies and clinical trials, including the Company’s Phase 1/1b clinical trial of CPI-818 and the Company’s planned meeting with the FDA to discuss a registration clinical trial with CPI-818 for T cell lymphoma during the third quarter of this year; the design of clinical trials, including the target number of patients to be enrolled; and the timing of the availability and announcement of clinical data and certain other product development milestones, including whether the Company is able to initiate clinical trials of CPI-818 as a monotherapy for solid tumors. 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 March 31, 2023, filed with the Securities and Exchange Commission on May 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 CPI-818 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; the results of preclinical studies and interim data from clinical trials not being predictive of future results; 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 A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/36a4fd03-0f86-4f2f-a144-bfb5e28fed71