AKT/PI3K/mTOR inhibitors(Thryv Therapeutics)

The ELECTRA and ELEVATE studies were designed to overcome different resistance mechanisms and improve patient outcomes with oral-oral combination options. Updated results from the ELECTRA study, evaluating elacestrant in combination with abemaciclib regardless of metastatic site, show a safety pro with previous results. Recommended phase 2 dose for this combination is presented. Updated analysis from the ELEVATE study demonstrates that all evaluable elacestrant plus targeted therapy combination arms are consistent with the known safety profiles of everolimus, alpelisib, ribociclib and palbociclib plus standard of care endocrine therapy. Recommended phase 2 dose for the combination of elacestrant and everolimus is presented. FLORENCE, Italy & NEW YORK--(BUSINESS WIRE)-- The Menarini Group (“Menarini”), a leading international pharmaceutical and diagnostics company, and Stemline Therapeutics, Inc. (“Stemline”), a wholly-owned subsidiary of the Menarini Group, focused on bringing transformational oncology treatments to cancer patients, will present updated results from phase 1b/2 ELECTRA and ELEVATE clinical studies evaluating elacestrant (ORSERDU®) in combination with other treatments. Both the ELECTRA and ELEVATE studies were designed to overcome different resistance mechanisms observed in estrogen receptor-positive (ER+), HER2-negative (HER2-) metastatic breast cancer (mBC) and improve patient outcomes through novel oral-oral combination treatment options. Data will be presented at the 2024 American Society of Clinical Oncology (ASCO), on June 2 from 9 a.m. to 12 p.m. CT. This press release features multimedia. View the full release here: The ELECTRA study is evaluating elacestrant in combination with abemaciclib in patients with ER+, HER2- metastatic breast cancer with brain metastases; however, the phase 1b portion of this study was conducted in all metastatic sites, including brain metastases. The updated phase 1b results continue to show a satisfactory safety profile, consistent with prior findings, and promising activity in patients with ER+, HER2- advanced or mBC regardless of metastatic site. Based on the results of this portion of the study, the recommended phase 2 dose (RP2D) will be reported as part of the data presentation. Currently, the phase 2 portion of ELECTRA is ongoing at the RP2D to further characterize the efficacy and safety in patients with ER+, HER2- metastatic breast cancer with brain metastases, since both elacestrant and abemaciclib cross the blood-brain barrier. “It is encouraging to see that, even in the early stages of the trial, the combination of elacestrant plus abemaciclib indicates a tolerable and manageable safety pro the patients in the clinical trial,” said Erika Hamilton, MD, Director of Breast Cancer Research and Executive Chair of the Breast Cancer Research Executive Committee for Sarah Cannon Research Institute. “The study continues to demonstrate elacestrant’s potential in combination with other therapies and we look forward to analyzing more data from this combination for this patient population in need of new options.” The ELEVATE study is evaluating elacestrant in combination with CDK4/6 inhibitors (palbociclib, abemaciclib and ribociclib) and with inhibitors of the PI3K/AKT/mTOR pathway (everolimus, alpelisib and capivasertib). The updated Phase 1b results show that the combinations evaluated are consistent with the known safety profiles of each targeted therapy plus standard of care endocrine therapy. Based on the results of this portion of the study, the RP2D will be reported for elacestrant in combination with everolimus. Additional cohorts, including elacestrant plus capivasertib, are currently under evaluation to further characterize the safety, assess efficacy and determine the RP2D for each combination arm. Phase 2 for the combination of elacestrant and abemaciclib in ER+, HER2- metastatic breast cancer, irrespective of the metastatic site, is already ongoing. “As we evaluate the various combinations of elacestrant plus CDK4/6 and PI3K/AKT/mTOR inhibitors, we continue to see consistent and manageable safety findings across all arms of the trial, and so far, elacestrant does not appear to add any incremental toxicity to the combination regimens in which it is being studied,” Hope S. Rugo, MD, Professor of Medicine and Winterhof Family Endowed Professor in Breast Cancer, Director, Breast Oncology and Clinical Trials Education, University of California San Francisco. “These data build on our understanding of elacestrant’s role in metastatic breast cancer and reinforce its potential as an endocrine therapy backbone in combination regimens.” “Since its approval in 2023, ORSERDU has had a meaningful impact as an endocrine therapy for people who are living with ER+, HER2- metastatic breast cancer harboring ESR1 mutations,” said Elcin Barker Ergun, CEO of the Menarini Group. “The data we are presenting at ASCO highlight elacestrant’s potential to further enhance patient outcomes when combined with other compounds.” About The Elacestrant Clinical Development Program Elacestrant is also being investigated in several company-sponsored clinical trials in metastatic breast cancer disease, alone or in combination with other therapies. ELEVATE (NCT05563220) is a phase 1b/2 clinical trial evaluating the safety and efficacy of elacestrant combined with alpelisib, everolimus, capivasertib, palbociclib, ribociclib or abemaciclib. ELECTRA (NCT05386108) is an open-label phase 1b/2, multicenter study evaluating elacestrant in combination with abemaciclib in patients with ER+, HER2- breast cancer. The phase 2 portion evaluates this treatment regimen in patients with brain metastases. ELCIN (NCT05596409) is a phase 2 trial evaluating the efficacy of elacestrant in patients with ER+, HER2- advanced/metastatic breast cancer who received one or two prior hormonal therapies and no prior CDK4/6 inhibitors in the metastatic setting. ADELA (NCT06382948) is a phase 3 randomized, double-blinded trial evaluating elacestrant in combination with everolimus in patients with ER+, HER2- mBC with ESR1-mut tumors. Elacestrant is also being evaluated in additional investigator-led trials, in trials conducted in collaboration with other companies, in metastatic breast cancer as well as in early disease. About ORSERDU (elacestrant) U.S. Indication: ORSERDU (elacestrant), 345 mg tablets, is indicated for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy. Full prescribing information for the U.S. can be found at . Important Safety Information Warning and Precautions Dyslipidemia: Hypercholesterolemia and hypertriglyceridemia occurred in patients taking ORSERDU at an incidence of 30% and 27%, respectively. The incidence of Grade 3 and 4 hypercholesterolemia and hypertriglyceridemia were 0.9% and 2.2%, respectively. Monitor lipid pro to starting and periodically while taking ORSERDU. Embryo-Fetal Toxicity: Based on findings in animals and its mechanism of action, ORSERDU can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with ORSERDU and for 1 week after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ORSERDU and for 1 week after the final dose. Adverse Reactions Serious adverse reactions occurred in 12% of patients who received ORSERDU. Serious adverse reactions in >1% of patients who received ORSERDU were musculoskeletal pain (1.7%) and nausea (1.3%). Fatal adverse reactions occurred in 1.7% of patients who received ORSERDU, including cardiac arrest, septic shock, diverticulitis, and unknown cause (one patient each). The most common adverse reactions (>10%), including laboratory abnormalities, of ORSERDU were musculoskeletal pain (41%), nausea (35%), increased cholesterol (30%), increased AST (29%), increased triglycerides (27%), fatigue (26%), decreased hemoglobin (26%), vomiting (19%), increased ALT (17%), decreased sodium (16%), increased creatinine (16%), decreased appetite(15%), diarrhea(13%), headache (12%), constipation (12%), abdominal pain (11%), hot flush (11%), and dyspepsia (10%). Drug interactions Concomitant use with CYP3A4 Inducers and/or inhibitors: Avoid concomitant use of strong or moderate CYP3A4 inhibitors with ORSERDU. Avoid concomitant use of strong or moderate CYP3A4 inducers with ORSERDU. Use in specific populations Lactation: Advise lactating women to not breastfeed during treatment with ORSERDU and for 1 week after the last dose. Hepatic Impairment: Avoid use of ORSERDU in patients with severe hepatic impairment (Child-Pugh C). Reduce the dose of ORSERDU in patients with moderate hepatic impairment (Child-Pugh B). The safety and effectiveness of ORSERDU in pediatric patients have not been established. To report SUSPECTED ADVERSE REACTIONS, contact Stemline Therapeutics, Inc. at 1-877-332-7961 or FDA at 1-800-FDA-1088 or . About The Menarini Group The Menarini Group is a leading international pharmaceutical and diagnostics company, with a turnover of $4.7 billion and over 17,000 employees. Menarini is focused on therapeutic areas with high unmet needs with products for cardiology, oncology, pneumology, gastroenterology, infectious diseases, diabetology, inflammation, and analgesia. With 18 production sites and 9 Research and Development centers, Menarini’s products are available in 140 countries worldwide. For further information, please visit . About Stemline Therapeutics Inc. Stemline Therapeutics, Inc. (“Stemline”) a wholly-owned subsidiary of the Menarini Group, is a commercial-stage biopharmaceutical company focused on the development and commercialization of novel oncology therapeutics. Stemline commercializes ORSERDU® (elacestrant) in the U.S. and Europe, an oral endocrine therapy indicated for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy. Stemline also commercializes ELZONRIS® (tagraxofusp-erzs), a novel targeted treatment directed to CD123 for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive hematologic cancer, in the United States and Europe, which is the only approved treatment for BPDCN in the U.S. and E.U. to date. Stemline also commercializes NEXPOVIO® (selinexor) in Europe, an XPO1 inhibitor for multiple myeloma. Stemline also has an extensive clinical pipeline of small molecules and biologics in various stages of development for a host of solid and hematologic cancers. View source version on businesswire.com: Contacts Media The Menarini Group Valeria Speroni Cardi Email: pressoffice@menarini.com Stemline Therapeutics, Inc. Cheya Pope Email: media@menarinistemline.com Source: The Menarini Group View this news release online at:

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.