Ivarmacitinib

AbbVie's rapidly expanding Humira successor, SKYRIZI, is already achieving impressive sales growth. This IL-23 inhibitor is set to capture an even greater portion of Humira's diminishing market share with its crucial expansion into treating ulcerative colitis. LAS VEGAS, July 15, 2024 /PRNewswire/ -- Ulcerative colitis is an idiopathic inflammatory bowel disease affecting ~1.5 million patients in the US and with an unknown exact cause. It affects the colonic mucosa and is clinically characterized by diarrhea, stomach discomfort, pain, and hematochezia. The disease's extent varies, affecting either the rectum, the splenic flexure of the left side of the colon, or the whole of the rectum and bowel. As per DelveInsight analysis, the total ulcerative colitis diagnosed prevalent cases in the 7MM comprised approximately 3 million cases in 2023 and are projected to increase by 2034. Per analyst estimates, approximately 60% of cases accounted for moderate to severe cases of ulcerative colitis among the 7MM. The current treatments for ulcerative colitis depend on the severity of the disease and are broadly divided into six classes, comprising conventional therapies, Anti-TNFs, Anti-integrin agents, IL-12/IL-23 dual inhibitors, S1P-receptor modulators, and JAK inhibitors. The emergence of several mechanisms of action, like LANCL2 protein stimulators, miR-124 enhancers, tumor necrosis factor (TNF)-like ligand 1A inhibitors, toll-like receptor 9 agonists, and others will be expanding the treatment landscape of ulcerative colitis. There have been significant advancements in treating ulcerative colitis over the years. However, safety remains a major challenge. The lack of a safer and curative treatment option severely impacts patients' quality of life and daily activities. While current treatments are effective for some patients with ulcerative colitis, others need multiple lines of therapy, indicating a need for alternative treatments to achieve disease control. Several major pharmaceutical companies are collaborating to develop new solutions to address these issues. Learn more about the FDA-approved ulcerative colitis drugs @ Drugs for Ulcerative Colitis Treatment A few FDA-approved drugs for ulcerative colitis treatment include SIMPONI (Janssen Pharmaceuticals), ENTYVIO (Takeda Pharmaceuticals), OMVOH (Eli Lilly) VELSIPITY (Arena Pharmaceuticals/Pfizer), and SKYRIZI (AbbVie). SIMPONI is a human monoclonal antibody that targets and neutralizes excess tumor necrosis factor (TNF)-alpha, a protein associated with inflammation and tissue damage in chronic inflammatory diseases. It is the first subcutaneous anti-TNF-alpha treatment administered every four weeks as maintenance therapy for ulcerative colitis. Approved for treating moderately to severely active ulcerative colitis in adults, SIMPONI is also being evaluated in ongoing trials for pediatric patients with the same condition. Vedolizumab is a humanized monoclonal antibody that targets and inhibits the alpha 4 beta 7 integrin, preventing it from binding to the intestinal mucosal addressing cell adhesion molecule 1 (MAdCAM-1). This integrin is found in a subset of circulating white blood cells that play a role in the inflammatory processes of ulcerative colitis and Crohn's disease. By blocking the alpha 4 beta 7 integrin, vedolizumab may reduce the infiltration of these white blood cells into gut tissues. It is currently approved as an IV and SC formulation for the treatment of moderately to severely active ulcerative colitis in adults who have not responded to, lost response to, or were intolerant to conventional therapy or a tumor necrosis factor-alpha (TNFα) antagonist. VELSIPITY (Etrasimod) is an innovative, once-daily oral medication that acts as a highly selective modulator of the sphingosine 1-phosphate (S1P) receptor. Discovered by Arena, it is designed for optimized interaction with S1P receptors 1, 4, and 5, potentially offering better efficacy and safety. Etrasimod targets specific immune cells both systemically and locally and has the potential to treat various immune-mediated inflammatory diseases, such as Crohn's disease and ulcerative colitis. It is currently approved by the FDA and EMA for adults with moderately to severely active ulcerative colitis who have not responded adequately, lost response, or were intolerant to conventional or advanced therapies. Recently, on 18 June 2024, the FDA approved SKYRIZI for treating adult patients with moderately to severely active ulcerative colitis. This approval extends the drug's reach to approximately 1 million US patients and makes SKYRIZI the first IL-23 inhibitor approved for both UC and Crohn's disease, the two types of inflammatory bowel disease (IBD). After a 12-week induction period, patients can self-administer the medication at home using an on-body injector device, which AbbVie's press release describes as "designed with patients in mind." The device attaches to the body and delivers the medication in about five minutes. Since its approval for Crohn's in 2022, Skyrizi has emerged as a strong competitor to Johnson & Johnson's blockbuster drug STELARA in the IBD market. The AbbVie medication has captured a "significant share" of STELARA's sales. To know more about ulcerative colitis treatment options, visit @ New Treatment for Ulcerative Colitis The ulcerative colitis market is crowded with so many companies including Arena Pharmaceuticals, Pfizer, Abivax, Reistone Biopharma, InDex Pharmaceuticals, AbbVie, Boehringer Ingelheim, Janssen Pharmaceuticals, Landos Biopharma, NImmune, Merck, Mesoblast, and others are running clinical trials to improve the treatment space. The ulcerative colitis pipeline possesses potential drugs in mid-stage developments to be launched shortly. Some of the promising drugs in the pipeline include TREMFYA, ABX464, BT-11 (Omilancor), PRA023, Remestemcel-L, SHR0302 (Ivarmacitinib), and others that hold the potential to create a significant positive shift in the ulcerative colitis market size. Discover which therapies are expected to grab major ulcerative colitis market share @ Ulcerative Colitis Market Report TREMFYA (guselkumab) is a human monoclonal antibody targeting the p19 subunit of interleukin (IL)-23, created by Janssen. IL-23 plays a crucial role in the pathogenesis of inflammatory diseases like ulcerative colitis and Crohn's disease. TREMFYA, an IL-23 inhibitor, is a human immunoglobulin G1 lambda (IgG1λ) monoclonal antibody, produced in a mammalian cell line using recombinant DNA technology. It specifically binds to the p19 subunit of IL-23 and blocks its interaction with the IL-23 receptor. In May 2024, Johnson & Johnson released the initial data from the Phase III QUASAR maintenance study in ulcerative colitis, which achieved its primary endpoint and all major secondary endpoints, including highly statistically significant rates of endoscopic remission. Based on these findings, the company has submitted a supplemental Biologics License Application (sBLA) to the FDA. SHR0302, developed by Reistone Biopharma, is an innovative and potent oral JAK1 inhibitor aimed at treating inflammatory bowel diseases like ulcerative colitis and Crohn's disease. Due to its selectivity for JAK1, it may offer a safer and more effective alternative to pan-JAK inhibitors. Ongoing long-term clinical studies are investigating whether JAK1 selectivity can minimize hematological side effects associated with JAK2 inhibition, aiming to confirm a favorable risk-benefit profile (Reistone Biopharma, 2021a). SHR0302 is currently being tested in a Phase III clinical trial (NCT05181137) for the treatment of moderate to severe ulcerative colitis in adults. Discover more about drugs for ulcerative colitis in development @ Ulcerative Colitis Clinical Trials The anticipated launch of these emerging therapies for ulcerative colitis are poised to transform the market landscape in the coming years. As these cutting-edge therapies continue to mature and gain regulatory approval, they are expected to reshape the ulcerative colitis market landscape, offering new standards of care and unlocking opportunities for medical innovation and economic growth. DelveInsight estimates that the market size for ulcerative colitis is expected to grow from USD 8.4 billion in 2023 with a significant CAGR by 2034. This growth can be attributed to the introduction of upcoming therapies and the rising prevalence of the disease. The anticipated launch of these therapies is also expected to attract new entrants to the ulcerative colitis market, resulting in increased competition and innovation. DelveInsight's latest published market report titled as Ulcerative Colitis Market Insight, Epidemiology, and Market Forecast – 2034 will help you to discover which market leader is going to capture the largest market share. The report provides comprehensive insights into the ulcerative colitis country-specific treatment guidelines, patient pool analysis, and epidemiology forecast to help understand the key opportunities and assess the market's underlying potential. The ulcerative colitis market report proffers epidemiological analysis for the study period 2020–2034 in the 7MM segmented into: Total Diagnosed Prevalent Cases of Ulcerative Colitis Age-specific Cases of Ulcerative Colitis Severity-specific Cases of Ulcerative Colitis Total Treated Patients of Ulcerative Colitis The report provides an edge while developing business strategies by understanding trends shaping and driving the 7MM ulcerative colitis market. Highlights include: 11-year Forecast 7MM Analysis Epidemiology-based Market Forecasting Historical and Forecasted Market Analysis upto 2034 Emerging Drug Market Uptake Peak Sales Analysis Key Cross Competition Analysis Industry Expert's Opinion Access and Reimbursement Download this ulcerative colitis market report to assess the epidemiology forecasts, understand the patient journeys, know KOLs' opinions about the upcoming treatment paradigms, and determine the factors contributing to the shift in the ulcerative colitis market. Also, stay abreast of the mitigating factors to improve your market position in the ulcerative colitis therapeutic space. Related Reports Ulcerative Colitis Epidemiology Forecast Ulcerative Colitis Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted ulcerative colitis epidemiology in the 7MM, i.e., the United States, EU5 (Germany, Spain, Italy, France, and the United Kingdom), and Japan. Ulcerative Colitis Pipeline Ulcerative Colitis Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key ulcerative colitis companies, including Eli Lilly and Company, Lipid Therapeutics, Hoffmann-La Roche, Arena Pharmaceuticals, InDex Pharmaceuticals, EA Pharma, Theravance Biopharma, Boehringer Ingelheim, Janssen Research & Development, Lycera, LG Chem, Iltoo Pharma, Immunic, Hutchison Medipharma, Tianjin Hemay Pharmaceutical, GlaxoSmithKline, Galapagos, Celgene, Gossamer Bio, Eisai, UCB, Suzhou Connect Biopharmaceuticals, Landos Biopharma, Seres Therapeutics, Abivax, Genentech, ParaTech A/S, I-Mab Biopharma, Sublimity Therapeutics Holdco, Reistone Biopharma, Qu Biologics, PurGenesis Technologies, Protagonist Therapeutics, Pfizer, Palobiofarma, Novartis Pharmaceuticals, Bristol-Myers Squibb, Bridge Biotherapeutics, Amgen, Allergan, Applied Molecular Transport, AbGenomics International, Protalix BioTherapeutics, LTT Bio-Pharma Co Ltd, Dongwha pharma, Seres Therapeutics, Innovation Pharmaceuticals, Holy Stone Healthcare, SLA Pharma, OSE Immunotherapeutics, Bridge Biotherapeutics, Mitsubishi Tanabe Pharma, Sterna Biologicals, Mesoblast, Oncostellae, First Wave Bio, Oppilan Pharma, NeuClone, Morphic Therapeutic, Metacrine, LG Chem, Koutif Therapeutics, Kiniksa Pharmaceuticals, Avaxia Biologics, Algernon Pharmaceuticals, Akeso Biopharma, Kaleido Biosciences, Rebiotix, Prometheus Biosciences, PNB Vesper Life Science, Pandion Therapeutics, Palatin Technologies, Theravance Biopharma, VHsquared, Seres Therapeutics, Hoffmann-La Roche, Provention Bio, Bacainn Therapeutics, Landos Biopharma, Bristol-Myers Squibb, Janssen Research & Development, GlaxoSmithKline, Assembly Biosciences, NuBiyota, Tarus Therapeutics, Servatus, Athos Therapeutics, Aclaris Therapeutics, Exeliom Biosciences SAS, Voronoi Group, Ventria Bioscience, TheraSource LLC, Synlogic Inc, Synedgen, Surrozen Inc, StemRIM Inc, Shaperon Inc, Sareum Holdings, Saniona, RhemaStem, Regentys, Progenity, Pharmaxis, Pharmabiome, PanTheryx, Oncodesign, Nyrada, Microbiotica, MAKScientific, KoBioLabs, Istesso, Intract Pharma, Innovimmune Biotherapeutics, Impetis Biosciences, Finch Therapeutics Group, Vivreon Biosciences, NuMedii, Intact Therapeutics, Giiant Pharma, among others. Crohn's Disease Market Crohn's Disease Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key Crohn's disease companies, including Celgene, AstraZeneca, Abbvie, Mesoblast, Alfasigma, Tiziana Life Sciences, Abivax, Arena Pharmaceuticals, Cytocom, Amgen, Priothera, SLA Pharma, HAV Vaccines Ltd, Enzo Biochem Inc., VHsquared Ltd., among others. Irritable Bowel Syndrome Market Irritable Bowel Syndrome Market Insights, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of the market trends, market drivers, market barriers, and key irritable bowel syndrome companies, including Arena Pharmaceuticals, 4D Pharma, OrphoMed, Boston Pharmaceuticals, RedHill Biopharma Limited, Takeda, Cosmo Technologies, CinRx Pharma, Rottapharm, Synthetic Biologics, Biomica, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP

First quarter net product revenues for ZORYVE® franchise of $21.6M, with $15M for ZORYVE (roflumilast) cream 0.3%, and $6.5M for ZORYVE (roflumilast) topical foam, 0.3%; sales growth of 675% vs. Q1 '23 and 59% vs. Q4 '23Continued gross-to-net (GTN) improvement with blended GTN across products now in the low 60 percent rangeSustained growth in demand for cream and remarkable uptake of foam launched in JanuaryJuly 7, 2024 Prescription Drug User Fee Act (PDUFA) action date for roflumilast cream, 0.15%, for treatment of mild to moderate atopic dermatitis in adults and children down to age 6Strong cash position following a public offering raising gross proceeds of $172.5 million and a strategic licensing agreement in Japan WESTLAKE VILLAGE, Calif., May 14, 2024 (GLOBE NEWSWIRE) -- Arcutis Biotherapeutics, Inc. (Nasdaq: ARQT), a commercial-stage biopharmaceutical company focused on developing meaningful innovations in immuno-dermatology, today reported financial results for the quarter ended March 31, 2024, and provided a business update. “Our strong performance in the first quarter, with the incredibly well received launch of ZORYVE foam for seborrheic dermatitis, and continued growth of ZORYVE cream in psoriasis, reinforces the demand for new and novel steroid-free treatment options and physician adoption of the ZORYVE portfolio,” said Frank Watanabe, president and chief executive officer. “The growth of ZORYVE cream and foam, along with a July 7th PDUFA date for ZORYVE cream as a potential treatment for atopic dermatitis, as well as our robust development pipeline, position Arcutis for a potentially transformative year in 2024.” Program Updates / Key Milestones Roflumilast cream – a highly potent and selective phosphodiesterase-4 (PDE4) inhibitor in a once-daily cream formulation, approved in the United States and Canada for the treatment of plaque psoriasis and under development for atopic dermatitis Demand for ZORYVE cream in plaque psoriasis continues to grow, with over 208,000 prescriptions filled to date since launch by close to 12,000 unique prescribers, reflecting the high levels of patient and physician satisfaction with the ZORYVE cream clinical profile. ZORYVE cream is covered by the three largest Pharmacy Benefit Managers and multiple other commercial insurers, and the Company anticipates beginning to obtain Medicare and Medicaid coverage during 2024. The Company experienced another significant GTN improvement in the first quarter compared to Q4 '23, and anticipates additional GTN improvement throughout 2024 as GTN for the cream approaches steady state.The Food & Drug Administration (FDA) has accepted the Company’s supplemental new drug application (sNDA) for roflumilast cream 0.15% for the treatment of mild to moderate atopic dermatitis in adults and children down to age 6, and assigned the application a PDUFA target action date of July 07, 2024. The sNDA is supported by positive results from three Phase 3 studies as well as a Phase 2 dose ranging study, and two Phase 1 pharmacokinetic studies. Roflumilast foam – a once-daily foam formulation of topical roflumilast designed to overcome the challenges of delivering topical drugs in hair-bearing areas of the body, approved in the United States for the treatment of seborrheic dermatitis and in development for scalp and body psoriasis The launch in January of ZORYVE foam in seborrheic dermatitis has been incredibly well received by healthcare providers and patients, with over 46,000 prescriptions filled since launch, reflecting the high unmet need in this disease. ZORYVE foam is also covered by the three largest Pharmacy Benefit Managers. For the partial first quarter of launch, GTN is favorable and improving rapidly.Based on the positive topline results from the ARRECTOR pivotal Phase 3 trial for the treatment of scalp and body psoriasis, the Company anticipates submitting an sNDA for scalp and body psoriasis to the FDA in the third quarter of 2024. ARQ-255 – a topical suspension formulation of ivarmacitinib, a potent and highly selective topical Janus kinase type 1 (JAK1) inhibitor, designed to preferentially deliver the drug deep into the hair follicle, in order to potentially treat alopecia areata at the site of inflammation In December 2022, Arcutis announced the enrollment of the first healthy volunteer subject in a Phase 1b study in alopecia areata. The first subject in the alopecia areata cohort enrolled in the second quarter of 2023. ARQ-234 – a fusion protein that is a potent and highly selective checkpoint agonist of the CD200 Receptor (CD200R), being developed as a potential biologic treatment in atopic dermatitis The Company continues preclinical development efforts. Recent Corporate Highlights In February, the Company completed a public offering raising gross proceeds of $172.5 million including the underwriters' 30-day option to purchase additional shares at the public offering price per share, which was fully exercised.In February, the Company announced a strategic collaboration and licensing agreement for the development, manufacture, and commercialization of topical roflumilast in Japan with Sato Pharmaceutical Co., Ltd.In April, the Company announced David Topper has been appointed Chief Financial Officer (CFO) effective April 10, 2024. He replaced John Smither, who had rejoined Arcutis as interim CFO in August 2023. First Quarter 2024 Summary Financial Results Product revenues for the quarter ended March 31, 2024 were $21.6 million compared to $2.8 million for the corresponding period in 2023. Revenues for the quarter were $15.0 million for ZORYVE (roflumilast) cream 0.3% and $6.5 million for ZORYVE (roflumilast) topical foam, 0.3%. Year-over-year increases were due to strong unit demand as well as improvements in GTN sales deductions. In addition, the first quarter of 2024 included Other revenues of $28.0 million related to the upfront and milestone payments in connection with the Sato Pharmaceutical and Huadong Pharmaceutical collaboration and licensing agreements. Cost of sales for the quarter ended March 31, 2024 were $3.3 million compared to $0.8 million for the corresponding period in 2023. Research and development (R&D) expenses for the quarter ended March 31, 2024 were $23.1 million compared to $35.3 million for the corresponding period in 2023. The year-over-year decrease was due to decreased clinical development costs related to our topical roflumilast program. Selling, general, and administrative (SG&A) expenses for the quarter ended March 31, 2024 were $54.8 million compared to $42.9 million for the corresponding period in 2023. The year-over-year increase was primarily due to sales and marketing expenses related to the launches of ZORYVE cream and foam. Net loss was $35.4 million, or $0.32 per basic and diluted share, for the quarter ended March 31, 2024 compared to $80.1 million, or $1.31 per basic and diluted share, for the corresponding period in 2023. Cash, cash equivalents, restricted cash, and marketable securities were $404.5 million as of March 31, 2024, compared to $272.8 million as of December 31, 2023. Net cash used in operating activities was $31.6 million during the first quarter. Conference Call and Webcast Arcutis management will host a conference call and webcast today at 4:30 pm ET to discuss the financial results for the quarter and provide a business update. The webcast for this conference call may be accessed at the “Events” section of the Company’s website. The replay of the webcast will be available on the Arcutis website following the call. About Arcutis Arcutis Biotherapeutics, Inc. (Nasdaq: ARQT) is a commercial-stage medical dermatology company that champions meaningful innovation to address the urgent needs of individuals living with immune-mediated dermatological diseases and conditions. With a commitment to solving the most persistent patient challenges in dermatology, Arcutis has a growing portfolio including two FDA approved products that harnesses our unique dermatology development platform coupled with our dermatology expertise to build differentiated therapies against biologically validated targets. Arcutis’ dermatology development platform includes a robust pipeline with multiple clinical programs for a range of inflammatory dermatological conditions including scalp and body psoriasis, atopic dermatitis, and alopecia areata. For more information, visit https://www.arcutis.com or follow Arcutis on LinkedIn, Facebook, and X. Forward Looking Statements Arcutis cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. These statements are based on the Company's current beliefs and expectations. Such forward-looking statements include, but are not limited to, statements regarding the potential for its topical drugs in development to address large markets with significant unmet need; the development, approval and potential commercialization of Arcutis' product candidates; the potential continued commercial success and growth of ZORYVE cream in plaque psoriasis and ZORYVE foam in seborrheic dermatitis, including market access and reimbursement, product demand growth and continued improvement in gross to net; and the timing of regulatory filings and potential approvals for a number of dermatology indications for roflumilast in the United States and Canada. These statements involve substantial known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance, or achievements to be materially different from the information expressed or implied by these forward-looking statements and you should not place undue reliance on our forward-looking statements. Risks and uncertainties that may cause our actual results to differ include risks inherent in the clinical development process and regulatory approval process, the timing of regulatory filings, the timing, expenses, and success of our commercialization efforts, including uncertainty of future commercial sales and related items that can impact net sales, and our ability to defend our intellectual property. For a further description of the risks and uncertainties applicable to our business, see the “Risk Factors” section of our Form 10-K filed with U.S. Securities and Exchange Commission (SEC) on February 27, 2024, as well as any subsequent filings with the SEC. We undertake no obligation to revise or update information herein to reflect events or circumstances in the future, even if new information becomes available. Contacts: MediaAmanda Sheldon, Head of Corporate Communicationsmailto:asheldon@arcutis.com InvestorsLatha Vairavan, VP Finance and Head of Investor Relationsmailto:lvairavan@arcutis.com Derek Colemailto:derek.cole@iradvisory.com ARCUTIS BIOTHERAPEUTICS, INC.Condensed Consolidated Balance Sheets(In thousands) March 31, December 31, 2024 2023 (unaudited) ASSETS Current assets: Cash and cash equivalents $190,097 $88,398 Restricted cash 617 925 Marketable securities 213,769 183,463 Trade receivable, net 37,154 25,807 Inventories 13,247 13,134 Prepaid expenses and other current assets 13,178 18,704 Total current assets 468,062 330,431 Property and equipment, net 1,369 1,539 Intangible assets, net 6,250 6,438 Operating lease right-of-use asset 2,264 2,361 Other assets 596 596 Total assets $478,541 $341,365 LIABILITIES AND STOCKHOLDERS’ EQUITY Current liabilities: Accounts payable $12,969 $11,992 Accrued liabilities 33,584 33,941 Operating lease liability 756 735 Total current liabilities 47,309 46,668 Operating lease liability, noncurrent 3,181 3,382 Long-term debt, net 202,803 201,799 Other long-term liabilities 306 849 Total liabilities 253,599 252,698 Stockholders’ equity: Common stock 12 9 Additional paid-in capital 1,242,349 1,070,558 Accumulated other comprehensive loss (133) 4 Accumulated deficit (1,017,286) (981,904) Total stockholders’ equity 224,942 88,667 Total liabilities and stockholders’ equity $478,541 $341,365 ARCUTIS BIOTHERAPEUTICS, INC.Condensed Consolidated Statements of Operations(In thousands, except share and per share data)(unaudited) Three Months Ended March 31, 2024 2023 Revenues: Product revenue, net $21,569 $2,781 Other revenue 28,000 — Total revenues 49,569 2,781 Operating expenses: Cost of sales 3,256 783 Research and development 23,141 35,345 Selling, general, and administrative 54,794 42,918 Total operating expenses 81,191 79,046 Loss from operations (31,622) (76,265) Other income (expense): Other income, net 4,044 3,207 Interest expense (7,480) (7,042) Loss before income taxes (35,058) (80,100) Provision for income taxes $324 $— Net loss $(35,382) $(80,100) Per share information: Net loss per share, basic and diluted $(0.32) $(1.31)Weighted-average shares used in computing net loss per share, basic and diluted 111,048,525 61,169,089