PI3Kγ

Infinity is considering whether to withdraw its appeal for Nasdaq not to delist the company. With hopes of a merger with MEI Pharma now sunk for good, Infinity Pharmaceuticals is jettisoning three-quarters of its staff and three board members to stay afloat while it scans the horizon for another financial life raft. The planned combination of MEI Pharma and Infinity had been in the works since February. Yet despite surviving the intervention of a surprise bidder at the last minute, MEI’s shareholders finally voted on the proposal on Sunday and scuppered the deal for good. Infinity had made clear the stakes from the start, warning in March that the proposed combination with MEI could be the last chance to avoid bankruptcy as its lead clinical candidate eganelisib eats up remaining cash reserves. In a post-market release Tuesday, Infinity said it continues to believe that eganelisib “offers a near-term value creation opportunity that would be attractive to potential third-party acquirers.” The biotech has already taken the PI3Kγ inhibitor up to the initiation of a planned global phase 2 trial in head and neck squamous cell carcinoma but needs another company to take the candidate over the line. In order to keep going while Infinity seeks a “strategic transaction to maximize eganelisib’s potential,” the biotech is laying off 21 employees—equivalent to 78% of its current workforce. Following their colleagues out the door will be three of the company’s eight board members. “The remaining five members of the board have agreed to serve without compensation for the remainder of their board service,” Infinity explained. If that wasn’t enough of a sign of the dire financial straits the company is now in, Infinity is also considering whether to withdraw an appeal for Nasdaq not to delist the company from the exchange. The biotech’s share price sunk below $1—the minimum required to remain on the Nasdaq—in November 2022 and has never resurfaced. Infinity ended 2022 with $38.3 million in cash and equivalents, a sizable drop on the $80.7 million in the bank at the start of the year. Back in March 2023, the company explained that failing to get the MEI deal over the line meant the cash runway would run out in the second half of this year as opposed to its previous timeline of 2024. “This shorter cash runway is a result of expenditures related to merger activities and the advancement of eganelisib,” the company said at the time.

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Infinity Pharmaceuticals Inc., (NASDAQ: INFI) (“Infinity” or the “Company”), a clinical-stage biotechnology company developing eganelisib, a potential first-in-class, oral, immuno-oncology macrophage reprogramming therapeutic, today announced upcoming presentations including data on eganelisib by Infinity’s collaborator, Professor Judith A. Varner of the UCSD Moores Cancer Center, La Jolla, California, at the 2023 Annual Meeting of the American Association of Cancer Research (AACR) to be held April 14 - 19, 2023 in Orlando, Florida. Highlights of the presentations include preclinical and translational data further reinforcing the mechanism of action of PI3K-γ inhibition: Single cell transcriptomics data showing PI3K-γ knockout switches tumor associated macrophages in head and neck squamous cell carcinoma (HNSCC) and non small cell lung cancer (NSCLC) tumor models to activated, antigen-presenting, T cell-stimulating macrophages. Preclinical data supporting tumor growth delay of HNSCC tumor models in PI3K-γ knockout mice is mediated by intra-tumoral interleukin-12, interferon gamma and CD8+ T cells, key drivers of immune response to cancer. Translational data from the MARIO-275 clinical trial showing increased systemic immune activation in patients treated with nivolumab in combination with eganelisib over nivolumab alone, with enrichment of genes from interferon signaling, antigen presentation, and T cell receptor pathways. Translational data from the MARIO-3 clinical trial, showing immune activation within the tumor microenvironment in patients treated with eganelisib, nab-paclitaxel and atezolizumab, with up-regulation of interferon signaling, antigen presentation, and T cell receptor pathways. Following translational data from MARIO-1 indicating increased expression of the TGF-β activating integrin αVβ8 in HNSCC patients treated with combination of eganelisib and nivolumab, initial preclinical studies showing anti-αVβ8 monoclonal antibody treatment prevents growth of HNSCC tumor model in PI3K-γ knock-out mice. “Our presentations describe exciting aspects of the role of PI3K-γ as a fundamental molecular switch controlling immune response by myeloid cells in the tumor microenvironment,” said Professor Varner. “Our preclinical data suggest key roles for antigen-presenting activated macrophages, intra-tumoral IL-12, IFN-γ release and activated CD8+ T cells in mediating the effect of PI3K-γ knockout or PI3K-γ inhibition in tumor models. In line with our preclinical studies, emerging translational data from the MARIO-275 and MARIO-3 clinical trials support the mechanism of action of eganelisib through reprogramming and activation of tumor associated macrophages to reshape the tumor microenvironment and favor anti-tumor activity. Altogether, these data continue to underscore the potential of eganelisib as a next generation macrophage reprogramming immunotherapeutic, in combination with checkpoint inhibitors or potentially new immuno-oncology agents like anti-αVβ8 monoclonal antibodies.” Details of the presentations are as follows: Presentation time: Saturday, April 15, 2023, 8:30am-8:50am EDT Title: Macrophages rule in cancer Session: ED034 - Antigen Presentation: The Macrophage-Dendritic Cell Debate Presenter: Judith A. Varner Presentation time: Tuesday, April 18, 2023, 10:20am-10:40am EDT Title: Basic and clinical impacts of targeting myeloid cells in tumors Session: Session SY14 - Next Generation of Myeloid Checkpoints in Cancer Presenter: Judith A. Varner About Infinity and Eganelisib Infinity Pharmaceuticals, Inc. (“Infinity” or the “Company”), is a clinical-stage biotechnology company developing eganelisib (IPI-549), a potential first-in-class, oral, immuno-oncology macrophage reprogramming therapeutic designed to address a fundamental biologic mechanism of immune suppression in cancer. MARIO-3 is a clinical study evaluating eganelisib in combination with atezolizumab and nab-paclitaxel in front-line triple negative breast cancer (TNBC) and in combination with atezolizumab and bevacizumab in front-line renal cell carcinoma (RCC). MARIO-275 is a randomized, controlled combination study of eganelisib combined with nivolumab in I/O naïve urothelial cancer. For more information on Infinity, please refer to Infinity's website at . Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include the therapeutic potential of eganelisib including its potential as a first-in-class, oral, immuno-oncology macrophage reprogramming therapeutic. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Company's current expectations. For example, there can be no guarantee that eganelisib will successfully complete necessary preclinical and clinical development phases. Further, there can be no guarantee that any positive developments in Infinity's product portfolio will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the cost, timing and results of clinical trials and other development activities that may be delayed or disrupted by the COVID-19 pandemic or otherwise; the content and timing of decisions made by the U.S. FDA and other regulatory authorities; Infinity's ability to obtain and maintain requisite regulatory approvals; unplanned cash requirements and expenditures; development of agents by Infinity's competitors for diseases in which Infinity is currently developing or intends to develop eganelisib; and Infinity's ability to obtain, maintain and enforce patent and other intellectual property protection for eganelisib. These and other risks which may impact management's expectations are described in greater detail under the caption "Risk Factors" included in Infinity's annual report and quarterly reports filed with the Securities and Exchange Commission (SEC), and in other filings that Infinity makes with the SEC, available through the Company’s website at . Any forward-looking statements contained in this press release speak only as of the date hereof, and Infinity does not undertake and expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

The multinational Phase III study is evaluating leniolisib tablets in children aged 4 to 11 years with APDS, a rare primary immunodeficiency LEIDEN, Netherlands, Feb. 21, 2023 /PRNewswire/ -- Pharming Group N.V. ("Pharming" or "the Company") (EURONEXT Amsterdam: PHARM)/(Nasdaq: PHAR) announces that the first patient has been enrolled in its Phase III clinical trial (NCT05438407) evaluating the investigational drug leniolisib, an oral, selective phosphoinositide 3-kinase delta (PI3Kδ) inhibitor, in children with activated phosphoinositide 3-kinase delta syndrome (APDS). There is currently no approved treatment for this complex and progressive disease caused by genetic variants. At sites in the United States, Europe, and Japan, the single-arm, open-label, multinational clinical trial will evaluate the safety, tolerability, and efficacy of leniolisib in approximately 15 children aged 4 to 11 years who have a confirmed APDS diagnosis. The study's primary efficacy endpoints are a reduction in index lymph node size and an increased proportion of naïve B cells out of total B cells from baseline at 12 weeks. Secondary endpoints include an assessment of the ability of leniolisib to modify health-related quality of life based on measures of physical, social, emotional, and school functioning using a validated patient questionnaire. Pharming plans to initiate a similar clinical trial in the third quarter of 2023 that will include children aged 1 to 6 years, with APDS, to evaluate a new pediatric formulation of leniolisib. Eligible patients enrolled in either of the pediatric trials will continue to receive leniolisib for a year after the initial 12-week treatment period through an open-label extension trial. Manish Butte, MD, PhD, E. Richard Stiehm Endowed Chair, Professor with tenure in the Department of Pediatrics, and Division Chief of Immunology, Allergy, and Rheumatology at UCLA, commented: "In treating APDS, the current standard of care is to use an array of supportive therapies. While these therapies can treat some of the manifestations of APDS, they do not target the underlying cause of the disease. Pharming's studies of leniolisib in children with APDS are important for evaluating the possibility of minimizing symptoms earlier in the disease progression." Pharming's program for the clinical development of leniolisib in pediatric APDS is supported by positive data from a Phase II/III clinical trial that investigated the drug as a treatment for patients with the disease aged 12 years and older. As announced on February 2, 2022, and recently detailed in Blood1, the international medical journal of the American Society of Hematology, the trial met both its co-primary endpoints, with patients who took leniolisib versus placebo achieving significant reductions in lymphoproliferation as measured by index lymph node size and increases in immunophenotype corrections as measured by the percentage of naïve B cells in peripheral blood. During the first half of 2022, positive opinions were received from the European Medicines Agency (EMA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA) on the Pediatric Investigation Plan (PIP) for leniolisib as a treatment for APDS in children. The PIP(s) included the plans for both pediatric clinical trials. Anurag Relan, MD, MPH, Chief Medical Officer of Pharming, commented: "I am pleased we have initiated the first trial in our Phase III pediatric clinical program evaluating leniolisib in children with APDS, and I look forward to our second pediatric trial getting underway. Building on the encouraging findings from our successful Phase II/III study in patients aged 12 years and older with APDS, we are committed to bringing leniolisib to even younger patients with the goal of intervening before they develop immune-related symptoms likely to progress throughout their lives. While continuing to focus on patients of all ages with APDS, we are dedicated to collaborating with regulatory authorities with the goal of generating regulatory filings to gain approval that could support the treatment of children under 12 years of age who are living with this disease." Based on the Phase II/III trial results and long-term open-label extension data, the U.S. Food and Drug Administration (FDA) is conducting a priority review of Pharming's New Drug Application for leniolisib as a treatment for adolescents and adults with APDS and has assigned a Prescription Drug User Fee Act (PDUFA) goal date of March 29, 2023. In addition, Pharming's Marketing Authorisation Application (MAA) for leniolisib in the same patient population is under evaluation by the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP). Pharming expects that the CHMP will issue its opinion on the leniolisib MAA in 2H 2023. About Activated Phosphoinositide 3-Kinase δ Syndrome (APDS) APDS is a rare primary immunodeficiency that affects approximately 1 to 2 people per million. APDS is caused by variants in either of two genes, PIK3CD or PIK3R1, that regulate maturation of white blood cells. Variants of these genes lead to hyperactivity of the PI3Kδ (phosphoinositide 3-kinase delta) pathway.2,3 Balanced signaling in the PI3Kδ pathway is essential for physiological immune function. When this pathway is hyperactive, immune cells fail to mature and function properly, leading to immunodeficiency and dysregulation.2,4 APDS is characterized by severe, recurrent sinopulmonary infections, lymphoproliferation, autoimmunity, and enteropathy.5,6 Because these symptoms can be associated with a variety of conditions, including other primary immunodeficiencies, people with APDS are frequently misdiagnosed and suffer a median 7-year diagnostic delay.7 As APDS is a progressive disease, this delay may lead to an accumulation of damage over time, including permanent lung damage and lymphoma.5-8 A definitive diagnosis can be made through genetic testing. About leniolisib Leniolisib is a small-molecule inhibitor of the delta isoform of the 110 kDa catalytic subunit of class IA PI3K. PI3Kδ is expressed predominately in hematopoietic cells and is essential to normal immune system function through conversion of phosphatidylinositol-4-5-trisphosphate (PIP2) to phosphatidylinositol-3-4-5-trisphosphate (PIP3). Leniolisib inhibits the production of PIP3 and PIP3 serves as an important cellular messenger activating AKT (via PDK1) and regulates a multitude of cell functions such as proliferation, differentiation, cytokine production, cell survival, angiogenesis, and metabolism. Unlike PI3Kα and PI3Kβ, which are ubiquitously expressed, PI3Kẟ and PI3Kγ are expressed primarily in cells of hematopoietic origin. The central role of PI3Kẟ in regulating numerous cellular functions of the adaptive immune system (B-cells and, to a lesser extent, T cells) as well as the innate immune system (neutrophils, mast cells, and macrophages) strongly indicates that PI3Kẟ is a valid and potentially effective therapeutic target for immune diseases such as APDS. To date, leniolisib has been well tolerated during both the Phase 1 first-in-human trial in healthy subjects and the Phase II/III registration-enabling study in patients with APDS. About Pharming Group N.V. Pharming Group N.V. (EURONEXT Amsterdam: PHARM/Nasdaq: PHAR) is a global biopharmaceutical company dedicated to transforming the lives of patients with rare, debilitating, and life-threatening diseases. Pharming is commercializing and developing an innovative portfolio of protein replacement therapies and precision medicines, including small molecules, biologics, and gene therapies that are in early to late-stage development. Pharming is headquartered in Leiden, Netherlands, and has employees around the globe who serve patients in over 30 markets in North America, Europe, the Middle East, Africa, and Asia-Pacific. For more information, visit and find us on LinkedIn. Forward-looking Statements This press release may contain forward-looking statements. Forward-looking statements are statements of future expectations that are based on management's current expectations and assumptions and involve known and unknown risks and uncertainties that could cause actual results, performance, or events to differ materially from those expressed or implied in these statements. These forward-looking statements are identified by their use of terms and phrases such as "aim", "ambition", ''anticipate'', ''believe'', ''could'', ''estimate'', ''expect'', ''goals'', ''intend'', ''may'', "milestones", ''objectives'', ''outlook'', ''plan'', ''probably'', ''project'', ''risks'', "schedule", ''seek'', ''should'', ''target'', ''will'' and similar terms and phrases. Examples of forward-looking statements may include statements with respect to timing and progress of Pharming's preclinical studies and clinical trials of its product candidates, Pharming's clinical and commercial prospects, and Pharming's expectations regarding its projected working capital requirements and cash resources, which statements are subject to a number of risks, uncertainties and assumptions, including, but not limited to the scope, progress and expansion of Pharming's clinical trials and ramifications for the cost thereof; and clinical, scientific, regulatory and technical developments. In light of these risks and uncertainties, and other risks and uncertainties that are described in Pharming's 2021 Annual Report and the Annual Report on Form 20-F for the year ended December 31, 2021, filed with the U.S. Securities and Exchange Commission, the events and circumstances discussed in such forward-looking statements may not occur, and Pharming's actual results could differ materially and adversely from those anticipated or implied thereby. All forward-looking statements contained in this press release are expressly qualified in their entirety by the cautionary statements contained or referred to in this section. Readers should not place undue reliance on forward-looking statements. Any forward-looking statements speak only as of the date of this press release and are based on information available to Pharming as of the date of this release. Pharming does not undertake any obligation to publicly update or revise any. Inside Information This press release relates to the disclosure of information that qualifies, or may have qualified, as inside information within the meaning of Article 7(1) of the EU Market Abuse Regulation. References Rao VK, et al. Blood. 2022. . Lucas CL, et al. Nat Immunol. 2014;15:88-97. Elkaim E, et al. J Allergy Clin Immunol. 2016;138(1):210-218. Nunes-Santos C, Uzel G, Rosenzweig SD. J Allergy Clin Immunol. 2019;143(5):1676-1687. Coulter TI, et al. J Allergy Clin Immunol. 2017;139(2):597-606. Maccari ME, et al. Front Immunol. 2018;9:543. Jamee M, et al. Clin Rev Allergy Immunol. 2019;May 21. Condliffe AM, Chandra A. Front Immunol. 2018;9:338. For further public information, contact: Pharming Group, Leiden, The Netherlands Michael Levitan, VP Investor Relations & Corporate Communications T: +1 (908) 705 1696 Heather Robertson, Investor Relations & Corporate Communications Manager E: [email protected] FTI Consulting, London, UK Victoria Foster Mitchell/Alex Shaw/Amy Byrne T: +44 203 727 1000 LifeSpring Life Sciences Communication, Amsterdam, The Netherlands Leon Melens T: +31 6 53 81 64 27 E: [email protected] US PR Ethan Metelenis E: [email protected] T: +1 (917) 882 9038 EU PR Dan Caley E: [email protected] T: +44 (0) 787 546 8942 Logo - The content and accuracy of news releases published on this site and/or distributed by PR Newswire or its partners are the sole responsibility of the originating company or organisation. 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