mTOR

On March 26th, the US FDA granted approval for Merck’s WINREVAIR™ (sotatercept-csrk), marking a significant milestone in pulmonary arterial hypertension (PAH) treatment. PAH, characterized by elevated blood pressure in the arteries connecting the heart and lungs, poses a grave risk of heart failure. While pulmonary vasodilators have improved patient prognosis, the challenge of disease progression persists, underscoring the importance of innovative treatments like Sotatercept. Sotatercept’s Mechanism of Action Sotatercept introduces a novel paradigm in PAH therapy. It functions as a fusion protein, incorporating the binding site of ACVR2A, thereby disrupting downstream signaling pathways, particularly the SMAD pathway. By sequestering activin, a member of the TGF-β superfamily, Sotatercept reinstates the equilibrium between growth-promoting and growth-inhibiting pathways within the pulmonary arteries. ACVR2A: Implications Across Disease Spectrum Beyond its role in PAH, ACVR2A emerges as a pivotal player in the pathogenesis of various ailments. This broad implication positions ACVR2A targeting as a promising strategy in arresting disease progression. Alongside Sotatercept, two other pharmaceutical pipelines are on the cusp of market approval, while six companies are advancing drugs targeting ACVR2A in preclinical phases, addressing conditions ranging from cancer to myelofibrosis. Sino Biological's offering to support PAH Research The pursuit of PAH therapeutics primarily revolves around targeting an array of molecular pathways, including ACVRs, BRD4, NF-kB, Nrf2, NFE2L1/Nrf1, mTOR, ASK-1, mineralocorticoid receptor, estrogen receptor, CD20, calcineurin, IL-6R, leukotriene A4 hydrolase, tryptophan hydrolase, and endothelial progenitor cells. Sino Biological plays a pivotal role in this endeavor by supplying recombinant proteins, antibodies, cytokines, and growth factors, catering to diverse research needs across various stages of PAH drug development. As a leading provider of comprehensive solutions and innovative tools used to advance life science and improve human health, Sino Biological is proud to offer premium products to support researchers in their quest to unlock novel treatments and improve patient outcomes.

Dosed the first patient in a Phase 1b/2 trial evaluating gedatolisib in combination with darolutamide for the treatment of metastatic castration resistant prostate cancer Presented nonclinical data demonstrating the superior therapeutic effects of gedatolisib compared to other PI3K/AKT/mTOR inhibitors at the 2023 SABCS Raised $65 million from the sale of equity; expect cash, cash equivalents, investments and available funds under our debt facility, to fund current operational activities into first half of 2026 Management to host webcast and conference call today, March 27, 2024, at 4:30 p.m. ET MINNEAPOLIS, March 27, 2024 (GLOBE NEWSWIRE) -- Celcuity Inc. (Nasdaq: CELC), a clinical-stage biotechnology company pursuing development of targeted therapies for oncology, today announced financial results for the fourth quarter and full year ended December 31, 2023 and other recent business developments. “In 2023, we made significant progress advancing development of gedatolisib while strengthening our balance sheet and adding to our leadership team,” said Brian Sullivan, CEO and Co-Founder of Celcuity. “Our Phase 3 VIKTORIA-1 trial remains on track to report topline data from the PI3KCA wild type patient sub-group in the second half of this year. We were also excited to begin development of gedatolisib for patients with metastatic castration resistant prostate cancer this past year. Enrollment has begun in our Phase 1b/2 trial evaluating gedatolisib in combination with darolutamide, and we look forward to sharing preliminary data from this trial in the first half of 2025.” Fourth Quarter 2023 Business Highlights and Other Recent Developments The VIKTORIA-1 Phase 3 trial remains on track to provide topline data for the PIK3CA wild type patient sub-group in the second half of 2024 and for the PIK3CA mutant patient sub-group in the first half of 2025. VIKTORIA-1 is evaluating gedatolisib in combination with fulvestrant with and without palbociclib in adults with HR+, HER2- advanced breast cancer who have received prior treatment with a CDK4/6 inhibitor. The Phase 3 VIKTORIA-1 clinical trial is enrolling patients at approximately 220 sites in 23 countries in North and South America, Europe, and Asia. The Phase 1b/2 clinical trial evaluating gedatolisib in combination with darolutamide for the treatment of metastatic castration resistant prostate cancer (mCRPC) was initiated in the fourth quarter of 2023. In February 2024, the first patient was dosed. The trial is expected to enroll up to 54 patients with mCRPC whose disease progressed after treatment with an androgen receptor signaling inhibitor. In December 2023, Celcuity presented data from nonclinical studies evaluating gedatolisib and other PI3K/AKT/mTOR (PAM) inhibitors in breast cancer cell lines during a poster session at the 2023 San Antonio Breast Cancer Symposium (SABCS). In a panel of breast cancer cell lines, gedatolisib was found to be more cytotoxic and at least 300-fold more potent, on average, compared to the single node PAM inhibitors. In February 2024, Eldon Mayer was appointed Chief Commercial Officer. His 30 years of biopharmaceutical commercial experience includes senior leadership roles at several companies where he led the launch of their first drug. Fourth Quarter and Full Year 2023 Financial Results Unless otherwise stated, all comparisons are for the fourth quarter and full year ended December 31, 2023, compared to the fourth quarter and full year ended December 31, 2022. Total operating expenses were $19.7 million for the fourth quarter of 2023, compared to $11.6 million for the fourth quarter of 2022. Operating expenses for the full year 2023 were $66.2 million, compared to $39.4 million for the full year 2022. Research and development (R&D) expenses were $18.1 million for the fourth quarter of 2023, compared to $10.6 million for the prior-year period. Of the approximately $7.5 million increase in R&D expenses, $6.8 million primarily related to activities supporting the VIKTORIA-1 Phase 3 trial and the initiation of the CELC-G-201 Phase 1b/2 clinical trial, and $0.7 million was related to increased employee and consulting expenses. R&D expenses for the full year 2023 were $60.6 million, compared to $35.3 million for the prior year. Of the approximately $25.3 million increase in R&D expenses, $22.9 million was related to activities supporting the VIKTORIA-1 Phase 3 trial and the initiation of the CELC-G-201 Phase 1b/2 clinical trial. The remaining $2.4 million increase in R&D expenses was related to increased employee and consulting expenses. General and administrative (G&A) expenses were $1.6 million for the fourth quarter of 2023, compared to $1.0 million for the prior-year period. Employee-related expenses accounted for $0.5 million of the increase. The remaining increase resulted from professional fees and other expenses associated with compliance related activities that support financing and clinical operations. G&A expenses for the full year 2023 were $5.6 million, compared to $4.1 million for the prior year. Of the approximately $1.5 million increase in G&A expenses, $1.1 million was related to increased employee-related expenses, and $0.4 million was related to professional fees and other expenses associated with compliance related activities that support financing and clinical operations. Net loss for the fourth quarter of 2023 was $18.8 million, or $0.65 loss per share, compared to a net loss of $11.6 million, or $0.69 loss per share, for the fourth quarter of 2022. Net loss for the full year 2023 was $63.8 million, or $2.69 loss per share, compared to a net loss of $40.4 million, or $2.64 loss per share, in 2022. Non-GAAP adjusted net loss for the fourth quarter of 2023 was $17.6 million, or $0.61 loss per share, compared to non-GAAP adjusted net loss of $10.3 million, or $0.61 loss per share, for the fourth quarter of 2022. Non-GAAP adjusted net loss for the full year 2023 was $57.8 million, or $2.44 loss per share, compared to non-GAAP adjusted net loss of $35.0 million, or $2.27 loss per share, for 2022. Non-GAAP adjusted net loss excludes stock-based compensation expense, non-cash interest expense, and non-cash interest income. Because these items have no impact on Celcuity’s cash position, management believes non-GAAP adjusted net loss better enables Celcuity to focus on cash used in operations. For a reconciliation of financial measures calculated in accordance with generally accepted accounting principles in the United States (GAAP) to non-GAAP financial measures, please see the financial tables at the end of this press release. Net cash used in operating activities for the fourth quarter of 2023 was $18.5 million, compared to $9.5 million for the fourth quarter of 2022. Net cash used in operating activities for the full year 2023 was $53.8 million, compared to $36.0 million for the full year 2022. In October of 2023, Celcuity closed a private placement of equity that resulted in gross proceeds of approximately $50 million. In December 2023, Celcuity closed on an additional $15 million of gross proceeds through its at-the-market offering. The Company expects to use the net proceeds to advance the clinical development of gedatolisib and for general corporate purposes. At December 31, 2023, Celcuity reported cash, cash equivalents and short-term investments of $180.6 million. We expect cash, cash equivalents, investments and available funds under our debt facility to provide adequate capital to fund current operational activities into the first half of 2026. Webcast and Conference Call Information The Celcuity management team will host a webcast/conference call at 4:30 p.m. ET today to discuss the fourth quarter and full year 2023 financial results and provide a corporate update. To participate in the teleconference, domestic callers should dial 1-888-886-7786 or 1-416-764-8658. A live webcast presentation can also be accessed using this weblink: . A replay of the webcast will be available on the Celcuity website following the live event. About Celcuity Celcuity is a clinical-stage biotechnology company focused on development of targeted therapies for treatment of multiple solid tumor indications. The company's lead therapeutic candidate is gedatolisib, a potent, pan-PI3K and mTOR inhibitor. Its mechanism of action and pharmacokinetic properties are highly differentiated from other currently approved and investigational therapies that target PI3K or mTOR alone or together. A Phase 3 clinical trial, VIKTORIA-1, evaluating gedatolisib in combination with fulvestrant with or without palbociclib in patients with HR+/HER2- advanced breast cancer is currently enrolling patients. More detailed information about the VIKTORIA-1 study can be found at ClinicalTrials.gov. A Phase 1b/2 clinical trial, CELC-G-201, evaluating gedatolisib in combination with darolutamide in patients with metastatic castration resistant prostate cancer, is enrolling patients. The company's CELsignia companion diagnostic platform is uniquely able to analyze live patient tumor cells to identify new groups of cancer patients likely to benefit from already approved targeted therapies. Further information about Celcuity can be found at . Follow us on LinkedIn and Twitter. Forward-Looking Statements This press release contains statements that constitute "forward-looking statements" including, but not limited to, the design of our clinical trials; the timing of initiating and enrolling patients in, and receiving results and data from, our clinical trials; the costs and expected results from any ongoing or planned clinical trials; the market opportunity for gedatolisib; our strategy, marketing and commercialization plans; other expectations with respect to Celcuity's lead product candidate, gedatolisib, and its CELsignia platform; our anticipated use of cash; and the strength of our balance sheet. In some cases, you can identify forward-looking statements by terminology such as "may," "should," "expects," "plans," "anticipates," "believes," "estimates," "predicts," "potential," "intends" or "continue," and other similar expressions that are predictions of or indicate future events and future trends, or the negative of these terms or other comparable terminology. Forward-looking statements are subject to numerous risks, uncertainties, and conditions, many of which are beyond the control of Celcuity. These include, but are not limited to, unforeseen delays in our clinical trials, our ability to obtain and maintain regulatory approvals to commercialize our products, and the market acceptance of such products, the development of therapies and tools competitive with our products, and those risks set forth in the Risk Factors section in Celcuity's Annual Report on Form 10-K for the year ended December 31, 2023 to be filed with the Securities and Exchange Commission on March 27, 2024. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Celcuity undertakes no obligation to update these statements for revisions or changes after the date of this press release, except as required by law. View source version of release on GlobeNewswire.com Contacts: Celcuity Inc. Brian Sullivan, bsullivan@celcuity.com Vicky Hahne, vhahne@celcuity.com (763) 392-0123 ICR Westwicke Maria Yonkoski, maria.yonkoski@westwicke.com (203) 682-7167 Celcuity Inc. Balance Sheets December 31, 2023 December 31, 2022 Assets Current Assets: Cash and cash equivalents $ 30,662,774 $ 24,571,557 Investments 149,919,974 144,015,954 Other current assets 10,007,849 6,603,026 Total current assets 190,590,597 175,190,537 Property and equipment, net 228,782 260,294 Operating lease right-of-use assets 400,019 246,266 Total Assets $ 191,219,398 $ 175,697,097 Liabilities and Stockholders' Equity: Current Liabilities: Accounts payable $ 5,076,699 $ 2,627,076 Finance lease liabilities - 2,449 Operating lease liabilities 184,950 191,749 Accrued expenses 8,927,094 4,060,280 Total current liabilities 14,188,743 6,881,554 Operating lease liabilities 225,922 61,002 Note payable, non-current 37,035,411 34,983,074 Total Liabilities 51,450,076 41,925,630 Total Stockholders' Equity 139,769,322 133,771,467 Total Liabilities and Stockholders' Equity $ 191,219,398 $ 175,697,097 Celcuity Inc. Statements of Operations Three Months Ended December 31, Years Ended December 31, 2023 2022 2023 2022 Operating expenses: Research and development $ 18,081,194 $ 10,604,043 $ 60,594,005 $ 35,289,548 General and administrative 1,648,079 1,035,161 5,636,326 4,101,543 Total operating expenses 19,729,273 11,639,204 66,230,331 39,391,091 Loss from operations (19,729,273 ) (11,639,204 ) (66,230,331 ) (39,391,091 ) Other income (expense) Interest expense (1,397,247 ) (678,003 ) (5,326,387 ) (2,106,111 ) Interest income 2,278,048 735,863 7,777,602 1,127,162 Other income (expense), net 880,801 57,860 2,451,215 (978,949 ) Net loss before income taxes (18,848,472 ) (11,581,344 ) (63,779,116 ) (40,370,040 ) Income tax benefits - - - - Net loss $ (18,848,472 ) $ (11,581,344 ) $ (63,779,116 ) $ (40,370,040 ) Net loss per share, basic and diluted $ (0.65 ) $ (0.69 ) $ (2.69 ) $ (2.64 ) Weighted average common shares outstanding, basic and diluted 28,900,075 16,872,018 23,679,472 15,418,543 Cautionary Statement Regarding Non-GAAP Financial Measures This press release contains references to non-GAAP adjusted net loss and non-GAAP adjusted net loss per share. Management believes these non-GAAP financial measures are useful supplemental measures for planning, monitoring, and evaluating operational performance as they exclude stock-based compensation expense, non-cash interest expense, and non-cash interest income from net loss and net loss per share. Management excludes these items because they do not impact Celcuity’s cash position, which management believes better enables Celcuity to focus on cash used in operations. However, non-GAAP adjusted net loss and non-GAAP adjusted net loss per share are not recognized measures under GAAP and do not have a standardized meaning prescribed by GAAP. As a result, management’s method of calculating non-GAAP adjusted net loss and non-GAAP adjusted net loss per share may differ materially from the method used by other companies. Therefore, non-GAAP adjusted net loss and non-GAAP adjusted net loss per share may not be comparable to similarly titled measures presented by other companies. Investors are cautioned that non-GAAP adjusted net loss and non-GAAP adjusted net loss per share should not be construed as alternatives to net loss, net loss per share or other statements of operations data (which are determined in accordance with GAAP) as an indicator of Celcuity’s performance or as a measure of liquidity and cash flows. Celcuity Inc. Reconciliation of GAAP Net Loss to Non-GAAP Adjusted Net Loss and GAAP Net Loss Per Share to Non-GAAP Adjusted Net Loss Per Share Three Months Ended December 31, Years Ended December 31, 2023 2022 2023 2022 GAAP net loss $ (18,848,472 ) $ (11,581,344 ) $ (63,779,116 ) $ (40,370,040 ) Adjustments: Stock-based compensation Research and development (1) 745,629 625,583 2,700,318 2,563,291 General and administrative (2) 496,904 513,838 2,201,116 2,074,914 Non-cash interest expense (3) 528,637 254,884 2,052,336 850,831 Non-cash interest income (4) (554,126 ) (142,928 ) (993,457 ) (142,928 ) Non-GAAP adjusted net loss $ (17,631,428 ) $ (10,329,967 ) $ (57,818,803 ) $ (35,023,932 ) GAAP net loss per share - basic and diluted $ (0.65 ) $ (0.69 ) $ (2.69 ) $ (2.64 ) Adjustment to net loss (as detailed above) 0.04 0.08 0.25 0.35 Warrant modification adjustment (5) - - - 0.02 Non-GAAP adjusted net loss per share $ (0.61 ) $ (0.61 ) $ (2.44 ) $ (2.27 ) Weighted average common shares outstanding, basic and diluted 28,900,075 16,872,018 23,679,472 15,418,543 (1) To reflect a non-cash charge to operating expense for Research and Development stock-based compensation. (2) To reflect a non-cash charge to operating expense for General and Administrative stock-based compensation. (3) To reflect a non-cash charge to other expense for amortization of debt issuance and discount costs and PIK interest related to the issuance of a note payable. (4) To reflect a non-cash adjustment to other income for accretion on investments. (5) To reflect an adjustment to basic and diluted net loss per share related to a warrant modification.

An analysis of how brains with different forms of autism develop has revealed common underlying mechanisms that may respond to existing medications. An analysis of how brains with different forms of autism develop has revealed common underlying mechanisms that may respond to existing medications. For the study, Rutgers Health researchers used a technique called induced pluripotent stem cells to transform the blood cells of people with both genetic and unexplained (or idiopathic) autism spectrum disorder (ASD) into early brain cells called neural precursor cells. As the precursor cells from both groups matured in the lab, defects in a common signaling pathway that controls structural proteins led them to struggle with an important step in cell differentiation, the growth of neurites, and the cell migration needed for proper brain architecture. Although some cell lines exhibited too much activity in this mTOR pathway, while others exhibited too little, the researchers could correct both problems and spur better cell differentiation with existing drugs that either stimulate or inhibit the activity of mTOR (mechanistic target of rapamycin). "Cells in a dish are not fully human cells that have developed in a fetus and functioned in a person, but they are a lot closer than mouse cells," said Emanuel DiCicco-Bloom, a professor of neuroscience and cell biology/pediatrics at Robert Wood Johnson Medical School and senior author of the study in eLife. "This finding is particularly interesting because the process of growing new synaptic spines when people learn things is completely analogous to the processes we observed in the cells we used for this experiment: growing axons and migrating during fetal development," DiCicco-Bloom said. "So even though this experiment mimicked a process you'd see during early to mid-pregnancy, the same process involving structural proteins is happening right now in you and me, which means that if we took cells from people with autism and found this abnormal regulation of mTOR in their cells in a dish, those people might be candidates as adults for mTOR regulating drugs to improve their function." The visible symptoms of ASD vary widely but typically feature some repetitive behaviors and some impairment in communication and social interaction. The condition's incidence has increased from about 1 in 150 children in 2000 to 1 in 36 children in 2020, according to the Centers for Disease Control and Prevention. Roughly 10 to 15 percent of people with ASD have genes that are known to elevate their risk for ASD. Other cases are idiopathic, meaning they are unexplained. Rutgers Health researchers began the study with blood from three unrelated people with idiopathic ASD, ages 4 to 14 years, with the expectation of finding person-specific differences in the processes occurring during development in utero. When the researchers used the pluripotent stem cell technique to transform blood cells into the sort of neuron precursors typically found in fetal brains, they unexpectedly found many similarities, including abnormalities in the mTOR pathway, which regulates cell creation, metabolism, neurite growth, remodeling and destruction, among many other functions. The researchers then gained access to blood cells from another three patients with ASD caused by a particular genetic abnormality associated with about 1 percent of ASD, deletion of genes on chromosome 16, called 16p11.2 deletion. They performed the same experiment and found the same disruptions in neuron development. Subsequent analysis showed that the mTOR signaling disruptions in some patients stemmed from excessive amounts of a particular molecule, while the disruptions in others stemmed from insufficient amounts. In either case, the researchers could use existing medications approved for use in other conditions to correct the problem and stimulate normal development. The study team has already begun a follow-up investigation to see if people with ASD stemming from other genetic causes exhibit similar disruptions in mTOR activity during development. If mTOR signaling disruption proves a common feature of ASD, tests of mTOR function could help clinicians diagnose the condition more accurately and differentiate it from other conditions with similar effects. "A couple of very rare genetic types of autism have already been linked to the mTOR pathway, but this is the first to connect mTOR with genes in the 16p11.2 area, which does not have mTOR on it, and with three presumably different types of idiopathic autism from three unrelated people," said Smrithi Prem, lead author of the study and a psychiatry resident at Penn Medicine who led the study as an MD/PhD student at Robert Wood Johnson Medical School. "These findings also echo something that has appeared in studies of other conditions, that not all people with mTOR dysregulation have excessive activation that needs inhibition," Prem said. "There are two kinds of mTOR dysregulation, but most trials we've run on people with mTOR dysregulation have only used inhibitors. Our findings showed that cells from two of the people we studied needed more mTOR, not less, and that may spur trials that give different types of mTOR treatment to different individual patients."