On July 20, 2021 DURECT Corporation (Nasdaq: DRRX) reported financial results for the three months ended June 30, 2021 and provided a corporate update (Press release, DURECT, JUL 29, 2021, View Source [SID1234585372]).

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Q2 2021 Accomplishments:

We expanded the number of U.S. clinical trial sites to 26 in the Phase 2b AHFIRM clinical study of DUR-928 in severe alcohol-associated hepatitis (AH), and we are enrolling at a good rate. We have now opened about 75% of the U.S. sites we plan to open. We expect to open our first ex-U.S. clinical sites (in the UK, Europe and Australia) in the coming months. In addition, we presented further encouraging DUR-928 clinical data from the completed NASH Phase 1b trial showing trends for reduction in insulin resistance and liver fibrosis biomarkers. Data from a Pharmacokinetic trial in patients with moderate and severe liver impairment showed a reduction in an important apoptosis biomarker with no adverse events or dose-limiting toxicity in these severely ill liver patients. We were also invited to present at the 2021 Epigenetic Therapeutic Targets Virtual Summit, which is for leading companies in the field of Epigenetics to present to their peers. To our knowledge, we were the only presenter utilizing an epigenetic regulator to restore function in injured cells as opposed to most who are using epigenetics to kill cancer cells. Our presentation was well received.

"Executing on the AHFIRM trial to the highest level of quality and in a timely fashion is our highest priority and we are pleased with the progress made this quarter," stated James E. Brown, D.V.M, President and CEO of DURECT. "Discussions with potential POSIMIR partners are ongoing."

Financial highlights for Q2 2021:

Total revenues were $2.3 million and net loss was $9.1 million for the three months ended June 30, 2021 as compared to total revenues of $24.5 million and net income of $14.3 million for the three months ended June 30, 2020. Total revenues and net income for the three months ended June 30, 2020 included the recognition of $23.1 million in deferred revenue related to the termination of a license agreement during that period.
At June 30, 2021, cash and investments were $88.6 million, compared to cash, cash held in escrow and investments of $56.9 million at December 31, 2020. Debt at June 30, 2021 was $20.4 million, compared to $20.8 million at December 31, 2020.
Update on Selected Programs:

Epigenetic Regulator Program. DUR-928, the lead product candidate in the Company’s Epigenetic Regulator Program, is an endogenous, orally bioavailable, first-in-class small molecule, which may have broad applicability in acute organ injuries such as alcohol-associated hepatitis (AH) as well as in chronic liver diseases such as non-alcoholic steatohepatitis (NASH).

Clinical Development

Alcohol-associated Hepatitis (AH)

Enrollment is ongoing in our Phase 2b study in subjects with severe acute AH to evaluate saFety and effIcacy of DUR-928 treatMent (AHFIRM). AHFIRM is a randomized, double-blind, placebo-controlled, international, multi-center Phase 2b study to evaluate the safety and efficacy of DUR-928 in approximately 300 patients with severe AH. The study is comprised of three arms targeting enrollment of approximately 100 patients each: (1) Placebo plus standard of care (SOC, which may include the use of methylprednisolone, a corticosteroid, at the discretion of the treating physician); (2) DUR-928 (30 mg); and (3) DUR-928 (90 mg). All patients in the trial receive supportive care. The primary outcome measure is 90-day survival rate for patients treated with DUR-928 compared to those treated with placebo plus SOC. The Company is targeting approximately 50 to 60 clinical trial sites in the U.S., U.K., E.U. and Australia.
Given the high mortality rate in severe AH patients and the absence of an approved therapeutic, we believe demonstration of a robust survival benefit in the AHFIRM trial would support an NDA filing.
Reflecting the life-threatening nature of AH and the lack of therapeutic options for this devastating condition, the FDA granted DUR-928 Fast Track Designation for the treatment of AH in December 2020.
In March 2021, a peer-reviewed research paper describing the binding sites and proposed mechanism of action of DUR-928 was published in The Journal of Lipid Research. The publication shows that DUR-928 (referred to in the paper as 25HC3S) binds to and inhibits the activity of DNA methyltransferases (DNMTs) DNMT-1, 3a and 3b, epigenetic regulating enzymes that add methyl groups to DNA (a process called DNA methylation). As such, by inhibiting DNMT activity, DUR-928 inhibits DNA methylation, thereby regulating the expression of genes that modulate crucial cellular activities, including those associated with cell death, stress response, and lipid biosynthesis. These modulations may lead to improved cell survival, and reduced lipid accumulation and inflammation, as has been observed in various in vivo animal models and in results from DURECT’s completed clinical trials in alcohol-associated hepatitis (AH) and non-alcoholic steatohepatitis (NASH).
In July 2021 we presented DUR-928’s mechanism of action, the previously reported positive results from our Phase 2a clinical study in alcohol-associated hepatitis (AH), and an overview of the AHFIRM trial at the 2021 Epigenetic Therapeutic Targets Virtual Summit.
In the Phase 2a clinical trial of DUR-928 in patients with AH, all 19 patients treated with DUR-928 survived the 28-day follow-up period, 74% of patients (14/19) were discharged in ≤ 4 days after receiving a single dose of DUR-928, and there were no drug-related serious adverse events.
Alcohol-associated hepatitis (also called alcoholic hepatitis or AH) is an acute form of alcoholic liver disease (ALD) associated with long-term heavy intake of alcohol, and often occurs after a recent period of increased alcohol consumption. AH is typically characterized by a recent onset of jaundice and hepatic failure. According to the most recent data provided by the Agency for Healthcare Research and Quality (AHRQ), a part of the US Department of Health and Human Services (HHS), there were approximately 132,000 hospitalizations for patients with AH in 2018. From a 2018 publication analyzing the mortality and costs associated with AH, the cost per patient is estimated at over $50,000 in the first year. ALD is one of the leading causes of liver transplants in the U.S., costing over $875,000 per patient. An analysis of 77 studies published between 1971 and 2016, which included data from a total of 8,184 patients, showed the overall mortality from AH was 26% at 28 days and 29% at 90 days after admission.
Non-Alcoholic Steatohepatitis (NASH)

In June 2021, we presented new data showing additional signals of potential efficacy from the NASH Phase 1b study of DUR-928 at the 2021 International Liver Conference (EASL) . This was a randomized and open-label clinical study conducted in the U.S. to evaluate safety, pharmacokinetics and signals of biological activity of DUR-928 in NASH patients with stage 1-3 fibrosis. Subjects in the 50 mg and 150 mg groups had 22% and 18% median reductions (not statistically significant) of homeostatic model assessment (HOMA-IR) from baseline, respectively, after 4 weeks of daily oral dosing of DUR-928. NASH subjects also had improvement from baseline in liver stiffness, assessed by transient elastography (TE), magnetic resonance elastography (MRE) and the liver fibrosis marker pro-C3. Positive topline results from this study were previously reported in May 2020.
We have also conducted a Phase 1b open-label, multi-center U.S. study to evaluate the safety, tolerability, and pharmacokinetics (PK) of DUR-928 in subjects with moderate (Child-Pugh B scores, n=10) and severe (Child-Pugh C scores, n=7) hepatic function impairment (HI), and matched control subjects (MCS, n=10) with normal hepatic functions. Each subject received a single oral dose of 200 mg DUR-928. Results from this study were presented at the International Liver Conference 2021 (EASL) in June 2021. DUR-928 was safe and well-tolerated by all moderate and severe HI subjects with no adverse events and no dose-limiting toxicity reported throughout the study. As expected, clearance of DUR-928 was decreased in HI subjects compared to MCS with normal hepatic function, resulting in a 4-10 fold higher drug exposure (Cmax and AUC) in HI subjects. Additionally, a single oral dose of 200 mg of DUR-928 in subjects with HI resulted in statistically significant median reductions from baseline of the apoptosis biomarker M30 (cCK-18) at 12 hours post-dose.
We are working with a number of disease experts to determine next steps for DUR-928 in NASH.
POSIMIR (bupivacaine solution) Post-Operative Pain Relief Depot. POSIMIR is DURECT’s post-operative pain relief depot that uses the Company’s patented SABER technology that delivers bupivacaine to provide up to 3 days of post-surgical analgesia.

In February 2021, POSIMIR was granted U.S. FDA approval in adults for administration into the subacromial space under direct arthroscopic visualization to produce post-surgical analgesia for up to 72 hours following arthroscopic subacromial decompression.
The approval was based on positive data from a randomized, multicenter, assessor-blinded, placebo–controlled clinical trial in patients undergoing arthroscopic subacromial decompression surgery with an intact rotator cuff. The primary outcome measures were mean pain intensity and total opioid rescue analgesia administered, both evaluated over the first 72 hours after surgery versus placebo. POSIMIR demonstrated a statistically significant improvement in both primary outcome measures: a 1.3 point, or 20%, reduction in mean pain intensity on a 0-10 point pain scale (p=0.01), and a 67% reduction in I.V. morphine-equivalent rescue opioid use, from a median of 12 mg in the placebo group to 4 mg in the POSIMIR group (p=0.01). In connection with this approval, the Company or its licensee, will be required to conduct two postmarketing non-clinical studies. Full Prescribing Information, including the Boxed Warning, is available at www.POSIMIR.com.
DURECT is in discussions with potential commercial partners for POSIMIR, for which DURECT currently holds worldwide rights.
Debt Amendment. In May 2021, the Company amended its existing $20 million term loan with Oxford Finance such that principal payments will commence 18 months later than previously scheduled (i.e., commencing June 1, 2023 rather than December 1, 2021) and the final maturity date has been moved back by 16 months (i.e., from May 1, 2024 to September 1, 2025). The interest rate and final payment remain unchanged, and the Company paid Oxford Finance an amendment fee of $712,500.

Conference Call
We will host a conference call today at 4:30 p.m. Eastern Time / 1:30 p.m. Pacific Time to discuss second quarter 2021 results and provide a corporate update:

The conference call will also be available by webcast on DURECT’s homepage at www.durect.com under the "Investors" tab. If you are unable to participate during the webcast, the call will be archived on DURECT’s website under "Event Calendar" in the "Investors" section.

On July 29, 2021 Cellectis S.A. (NASDAQ: CLLS – EURONEXT GROWTH: ALCLS) (the "Company"), a gene-editing platform company with clinical-stage immuno-oncology programs using allogeneic chimeric antigen receptor (CAR) T-cells and gene therapy programs for monogenic diseases, reported that it will report its financial results for the second quarter and first six-month period ending June 30, 2021, on Thursday, August 5, 2021, after the close of the US market (Press release, Cellectis, JUL 29, 2021, View Source [SID1234585371]). The announcement will be followed by a conference call at 8:00 AM EDT / 2:00 PM CET on Friday, August 6, 2021, prior to the open of the US market.

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On July 29, 2021 Gilead Sciences, Inc. (Nasdaq: GILD) reported its results of operations for the second quarter 2021 (Press release, Gilead Sciences, JUL 29, 2021, View Source [SID1234585370]).

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"We maintained our positive momentum in the second quarter, with both a solid financial performance and strong progress across our increasingly diverse portfolio. Our flagship HIV therapy, Biktarvy, saw continued growth and gains in market share, despite the ongoing impact of the pandemic," said Daniel O’Day, Chairman and Chief Executive Officer, Gilead Sciences. "The series of promising pipeline updates included the data from the landmark ZUMA-7 study for the treatment of second-line large B-cell lymphoma. In virology, recent results from our lenacapavir study reinforce its potential as a long-acting therapy for people living with HIV, and positive interim results from our Hepcludex studies in HDV moved us closer to a U.S. filing."

Second Quarter 2021 Financial Results

Total second quarter 2021 revenue of $6.2 billion increased 21% compared to the same period in 2020, primarily due to Veklury (remdesivir), higher demand for Biktarvy (bictegravir 50 mg/FTC/tenofovir alafenamide 25 mg ("TAF")) and our hepatitis C virus ("HCV") products, as well as continued uptake in the United States of Trodelvy (sacituzumab govitecan-hziy) and Tecartus (brexucabtagene autoleucel).
Diluted Earnings Per Share ("EPS") increased to $1.21 for the second quarter 2021 compared to net loss per share of $2.66 for the same period in 2020. This was primarily driven by the impact of higher in-process research and development ("IPR&D") expenses in the second quarter 2020 related to the Forty Seven, Inc. acquisition and revenue growth in the second quarter 2021, offset by fair value loss adjustments on Gilead’s equity investment in Galapagos NV.
Non-GAAP diluted EPS increased 68% to $1.87 for the second quarter 2021 compared to the same period in 2020, primarily due to higher operating income partially offset by lower interest income.
As of June 30, 2021, Gilead had $7.4 billion of cash, cash equivalents and marketable debt securities compared to $7.9 billion as of December 31, 2020.
During the second quarter 2021, Gilead generated $2.3 billion in operating cash flow.
During the second quarter 2021, Gilead paid cash dividends of $894 million and utilized $43 million to repurchase common stock.
Product Sales Performance

Total second quarter 2021 product sales increased 21% to $6.2 billion compared to the same period in 2020. Total product sales excluding Veklury increased 5% to $5.3 billion for the second quarter 2021 compared to the same period in 2020, reflecting continued uptake of Trodelvy and Tecartus in the United States as well as improving trends in HIV and HCV, offset, as expected, by loss of exclusivity of Truvada (emtricitabine 200mg ("FTC")/tenofovir disoproxil fumarate 300mg ("TDF")) and Atripla (efavirenz 600mg/FTC/TDF) in the United States.

HIV product sales decreased 2% to $3.9 billion for the second quarter 2021 compared to the same period in 2020, reflecting the expected loss of exclusivity of Truvada and Atripla in the United States, offset in part by increased demand.

Biktarvysales increased 24% year-over-year in the second quarter 2021, reflecting higher demand in all geographies.
Descovy (FTC/TAF) sales increased 4% year-over-year in the second quarter 2021, driven by increased pre-exposure prophylaxis ("PrEP") demand in the United States and the impact in the same period last year of the COVID-related channel inventory drawdown, offset by lower average net selling price.
Truvada and Atripla sales decreased 72% year-over-year to $108 million and 42% year-over-year to $60 million, respectively, in the second quarter 2021 due to generic entrants in the United States following loss of exclusivity in late 2020.
HCV product sales increased 23% to $549 million for the second quarter 2021 compared to the same period in 2020, driven primarily by improved market starts in the United States and Europe as well as an unfavorable change in estimate of government rebates in the second quarter 2020.

Hepatitis B virus ("HBV") and hepatitis delta virus ("HDV") product sales increased 8% to $237 million for the second quarter 2021 compared to the same period in 2020. Vemlidy (tenofovir alafenamide 25 mg) sales increased 32% in the second quarter 2021 compared to the same period in 2020 driven by increased demand primarily in geographies outside the United States and Europe. Hepcludex (bulevirtide) contributed $7 million in the second quarter 2021 reflecting the first full quarter of sales for Gilead.

Cell Therapy product sales increased 39% to $219 million for the second quarter 2021 compared to the same period in 2020.

Yescarta (axicabtagene ciloleucel) sales increased to $178 million in the second quarter 2021, reflecting continued uptake in relapsed or refractory indolent follicular lymphoma ("FL") in the United States following its approval by the U.S. Food and Drug Administration ("FDA") in the first quarter 2021 and expansion in Europe.
Tecartus sales were $41 million for the second quarter 2021, driven by the launch in mantle cell lymphoma in the United States and Europe.
Trodelvy sales for the second quarter 2021 were $89 million. Launch activities continue following the full FDA approval for second-line metastatic triple-negative breast cancer ("mTNBC") and accelerated approval for metastatic urothelial cancer.

Veklury sales were$829 millionfor the second quarter 2021. Sales of Veklury are generally affected by COVID-19 related rates of infections, hospitalizations and vaccinations.

Other product sales increased 20% to $291 million for the second quarter 2021 compared to the same period in 2020.

AmBisome (amphotericin B) sales increased in the second quarter 2021 compared to the same period in 2020 driven by an increase in shipments outside the United States, primarily in India and Europe.
Second Quarter 2021 Product Gross Margin, Operating Expenses and Tax

Product gross margin was 77.4% for the second quarter 2021 compared to 79.0% in the same period in 2020, reflecting additional amortization of intangibles acquired from Immunomedics, Inc. and MYR GmbH. Non-GAAP product gross margin was 86.4% for the second quarter 2021 compared to 84.3% in the same period in 2020, driven by lower royalty expense.
Research and Development ("R&D") expenses for the second quarter 2021 were $1.1 billion compared to $1.3 billion in the same period in 2020. Non-GAAP R&D expenses for the second quarter 2021 were $1.1 billion compared to $1.2 billion in the same period in 2020. Lower R&D expenses reflect completion or wind-down of remdesivir-related programs, partly offset by increases in Trodelvy and magrolimab clinical activities.
Sales, General and Administrative ("SG&A") expenses for the second quarter 2021 were $1.4 billion compared to $1.2 billion in the same period in 2020. The increase in SG&A expenses was driven primarily by a significant donation of equity securities to the Gilead Foundation. Non-GAAP SG&A expenses for the second quarter 2021 were $1.1 billion compared to $1.2 billion in the same period in 2020. The decrease in non-GAAP SG&A expenses was driven by lower legal expenses primarily due to a prior year settlement associated with a Department of Justice investigation, offset by increases in promotional and commercialization activities in geographies outside the United States.
The GAAP effective tax rate ("ETR") and non-GAAP ETR for the second quarter 2021 were 16.5% and 19.6%, respectively, compared to (12.5)% and 22.8%, respectively, for the same periods in 2020.
Key Updates Since Our Last Quarterly Release

Viral Diseases

Gilead presented additional lenacapavir clinical development program data at the International AIDS Society ("IAS") 2021 Conference on HIV Science. Phase 2 data from CALIBRATE, an ongoing, open-label, active-controlled trial in treatment-naïve people with HIV-1 infection showed lenacapavir, given subcutaneously or orally, in combination with oral daily emtricitabine/tenofovir alafenamide ("F/TAF") led to high rates of viral suppression by Week 28. These results support the ongoing evaluation and further development of lenacapavir in combination with other long-acting partner agents for the treatment of HIV-1 infection and will support Gilead’s long-acting oral and injectable development program.
Gilead also announced at IAS 2021 new results from the ongoing Phase 2/3 CAPELLA trial evaluating lenacapavir in heavily treatment-experienced people living with multi-drug resistant HIV. The findings demonstrate that lenacapavir administered subcutaneously every six months in combination with other antiretrovirals achieved high rates of virologic suppression at Week 26.
Gilead filed a New Drug Application to FDA seeking approval of lenacapavir for the treatment of HIV-1 infection in heavily treatment-experienced people with multi-drug resistant infection.
Gilead announced interim results from the Phase 3 study (MYR301) of bulevirtide for the treatment of HDV at the International Liver Congress ("ILC") 2021 annual meeting. After 24 weeks, 36.7% of patients receiving a 2mg dose of bulevirtide and 28% of patients receiving a 10mg dose of bulevirtide showed a combined virological and biological response compared to 0% in the no treatment group.
Gilead also announced at ILC 2021 the interim results from the Phase 2b study (MYR204) of bulevirtide for the treatment of HDV. At week 24, results showed that bulevirtide alone or in combination with peginterferon alfa-2a, is associated with a significant HDV RNA decline and improvements in biochemical disease activity.
Gilead received FDA approval for a new formulation of Epclusa, expanding the pediatric indication for the treatment of HCV to now include children as young as 3 years of age.
Oncology

Kite announced top-line results from the primary analysis of ZUMA-7 trial of Yescarta in second-line relapsed or refractory large B-cell lymphoma ("LBCL"). At a median follow-up of two years, Yescarta improved event free survival by 60% over the standard of care chemotherapy plus stem cell transplant. The study also met the key secondary endpoint of objective response rate. Full data will be presented later this year and discussions are underway with global regulatory authorities.
Kite announced that Fosun Kite Biotechnology Co., Ltd., a joint venture between Kite and Shanghai Fosun Pharmaceutical (Group) Co., Ltd., received approval from the China National Medical Products Administration for axicabtagene ciloleucel (FKC876) for the treatment of adult patients with relapsed or refractory LBCL after two or more lines of systemic therapy. Yescarta is the first and only commercially available chimeric antigen receptor ("CAR") T-cell therapy approved in China.
Kite announced a partnership with Shoreline Biosciences, Inc. to develop allogeneic candidates for a range of hematologic malignancies. The collaboration will focus initially on CAR NK targets, with Kite having an option to expand the collaboration to include an induced pluripotent stem cell CAR Macrophage program.
Kite announced follow-up results from the pivotal ZUMA-5 trial of Yescarta in relapsed or refractory FL at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) ("ASCO") 2021 annual meeting. At a minimum follow-up of 18 months, 94% of patients had achieved a response, and secondary endpoints of median progression-free survival and overall survival were not yet reached.
Kite announced at ASCO (Free ASCO Whitepaper) 2021, with a publication in The Lancet, primary analysis of ZUMA-3 evaluating Tecartus in adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia. In the pivotal Phase 2 portion of the trial, 71 patients with relapsed or refractory disease were enrolled and Kite observed a response rate of 71%. Importantly, the majority of these responses were associated with undetectable minimal residual disease. The findings have been designated for Priority Review by FDA with a Prescription Drug User Fee Act ("PDUFA") date of October 1, 2021.
Gilead announced analyses from Phase 3 ASCENT study at ASCO (Free ASCO Whitepaper) 2021 in patients with relapsed or refractory mTNBC. Treatment with Trodelvy demonstrated significantly greater survival benefit over chemotherapy in patients treated in the second-line setting and in patients greater than 65 years old.
Corporate

Kite announced a purchase agreement with BioNTech SE to acquire Kite’s solid tumor neoantigen T cell receptor R&D platform and clinical manufacturing facility in Gaithersburg, Maryland.
Gilead welcomed William Grossman, MD, PhD, as Senior Vice President, Oncology Clinical Research. Dr. Grossman brings extensive experience as a clinician and a veteran biopharmaceutical executive.
Gilead announced that the company’s Board of Directors has declared a quarterly dividend of $0.71 per share of common stock for the third quarter of 2021. The dividend is payable on September 29, 2021, to stockholders of record at the close of business on September 15, 2021. Future dividends will be subject to Board approval.
Guidance and Outlook

Gilead has updated its full-year guidance, and now expects:

Total product sales between $24.4 billion and $25.0 billion, compared to $23.7 billion and $25.1 billion previously, reflecting solid results in the first half of the year and our updated expectations for the second half of 2021.
Total product sales, excluding Veklury, between $21.7 billion and $21.9 billion, compared to $21.7 billion to $22.1 billion previously, primarily reflecting the longer than expected pandemic impact on our HIV business, including the latest increase in COVID-19 cases.
Total Veklury sales between $2.7 billion and $3.1 billion, compared to $2.0 billion to $3.0 billion previously, reflecting the ongoing role of Veklury in the pandemic, in addition to the continued uncertainties around the path of the pandemic since Veklury revenue tends to track hospitalization rates.
GAAP earnings per share between $4.70 and $5.05, compared to $4.75 to $5.45 previously.
Non-GAAP earnings per share between $6.90 and $7.25, compared to $6.75 to $7.45 previously.
A reconciliation between GAAP and non-GAAP financial information for the 2021 guidance is provided in the accompanying tables. Also see the Forward-Looking Statements described below. The financial guidance is subject to a number of risks and uncertainties, including uncertainty around the duration and magnitude of the COVID-19 pandemic. While the pandemic can be expected to continue to impact Gilead’s business and broader market dynamics, the rate and degree of these impacts as well as the corresponding recovery from the pandemic may vary across Gilead’s business.

Non-GAAP Financial Information

The information presented in this document has been prepared in accordance with U.S. generally accepted accounting principles ("GAAP"), unless otherwise noted as non-GAAP. Management believes non-GAAP information is useful for investors, when considered in conjunction with Gilead’s GAAP financial information, because management uses such information internally for its operating, budgeting and financial planning purposes. Non-GAAP information is not prepared under a comprehensive set of accounting rules and should only be used to supplement an understanding of Gilead’s operating results as reported under GAAP. Non-GAAP financial information excludes acquisition-related expenses including amortization of acquired intangible assets and inventory step-up charges in cost of goods sold, acquired IPR&D expenses, and other items that are considered unusual or not representative of underlying trends of Gilead’s business, fair value adjustments of equity securities and discrete and related tax charges or benefits associated with changes in tax related laws and guidelines. Acquired IPR&D expenses reflect IPR&D impairments as well as the initial costs of externally developed IPR&D projects, acquired directly in a transaction other than a business combination, that do not have an alternative future use, including upfront and other payments related to various collaborations and the initial costs of rights to IPR&D projects. Although Gilead consistently excludes the amortization of acquired intangible assets from the non-GAAP financial information, management believes that it is important for investors to understand that such intangible assets were recorded as part of acquisitions and contribute to ongoing revenue generation.Non-GAAP measures may be defined and calculated differently by other companies in the same industry. Reconciliations of the non-GAAP financial measures to the most directly comparable GAAP financial measures are provided in the accompanying tables.

Conference Call

At 1:30 p.m. Pacific Time today, Gilead will host a conference call to discuss Gilead’s results. A live webcast will be available on View Source and will be archived on www.gilead.com for one year.

On July 29, 2021 Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) reported consolidated financial results for the second quarter ended June 30, 2021 and raised full-year 2021 guidance for product revenues to $7.2 to $7.4B (Press release, Vertex Pharmaceuticals, JUL 29, 2021, View Source [SID1234585369]).

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"In the second quarter of 2021, we saw continued, significant growth and strong business performance in our cystic fibrosis franchise. We have now secured reimbursement agreements for the triple combination in more than 15 countries outside the U.S. and started expansion into younger age groups with the U.S. approval in patients 6 to 11 years of age last month. With these advancements, we are poised to reach more patients in 2021 than previously forecasted and are therefore raising our 2021 revenue guidance. Looking forward, we continue to see significant growth ahead in CF, with more than 30,000 CF patients who may benefit from the triple combination but who are not yet treated," said Reshma Kewalramani, M.D., Chief Executive Officer and President of Vertex.

"We also made important progress with our pipeline programs in the first half of this year. Our pipeline programs are advancing quickly, with five programs in mid- or late-stage clinical trials. We continue to see impressive clinical results with CTX001, our most advanced program outside of CF, in which we have now dosed more than 45 patients. Our pre-commercial efforts for this program are underway, as we prepare to serve patients with sickle cell disease and beta thalassemia and address the significant market opportunity. We look forward to multiple R&D milestones and data readouts in the coming 6 to 9 months," said Dr. Kewalramani.

Product revenues increased 18% compared to the second quarter of 2020, primarily driven by the uptake of KAFTRIO in Europe and continued strong performance of TRIKAFTA in the U.S. Net product revenues in the second quarter of 2021 increased 4% to $1.26 billion in the U.S. and increased 71% to $536 million outside the U.S., compared to the second quarter of 2020.

GAAP net income decreased compared to the second quarter of 2020, primarily due to a $900 million payment in connection with the amendment of Vertex’s collaboration with CRISPR Therapeutics that was recorded as a GAAP R&D expense in the second quarter of 2021.

Non-GAAP net income increased compared to the second quarter of 2020, largely driven by strong growth in product revenues.

Cash, cash equivalents and marketable securities were $6.71 billion, an increase of $49 million compared to $6.66 billion as of December 31, 2020, primarily driven by strong operating cash flow from Vertex’s revenue growth and profitability, and offset by the $900 million payment to CRISPR and repurchases of our common stock authorized under our 2020 share repurchase program.

Combined GAAP R&D and SG&A expenses increased compared to the second quarter of 2020, primarily due to the $900 million payment to CRISPR in the second quarter of 2021.

Combined Non-GAAP R&D and SG&A expenses increased compared to the second quarter of 2020, primarily due to the expansion of Vertex’s pipeline in CF and other disease areas and incremental investment to support the global launches of Vertex’s medicines.

GAAP income taxes reflected an increased benefit compared to the second quarter of 2020, primarily due to the income tax impact of the $900 million payment to CRISPR partially offset by a decrease in discrete tax benefits. Please refer to Note 2 for further details.

Non-GAAP income taxes increased compared to the second quarter of 2020 primarily due to Vertex’s increased operating income.

Full-Year 2021 Financial Guidance

Vertex today increased its full-year 2021 product revenue guidance based on strong year-to-date performance and the expected impact of recent reimbursement agreements. Vertex’s guidance is summarized below:

Cystic Fibrosis (CF) Marketed Products

Vertex anticipates that the number of CF patients treated with our medicines will continue to grow as we enter into additional reimbursement agreements, achieve new approvals for the treatment of younger patients, and expand treatment options for the approximately 10 percent of patients who do not benefit from CFTR modulators, all of which will lead to continued growth of our CF business in the years ahead.

In June, the U.S. FDA approved expansion of the indication of TRIKAFTA (elexacaftor/tezacaftor/ivacaftor and ivacaftor) to include children with CF ages 6 through 11 years. Health Canada granted Marketing Authorization for TRIKAFTA for people with CF ages 12 years and older who have at least one F508del mutation. TRIKAFTA/KAFTRIO is now approved and reimbursed or accessible in more than 15 countries outside the U.S., including Italy and France.

R&D pipeline

Vertex continues to progress a broad pipeline of potentially transformative small molecule, cell and genetic therapies aimed at serious diseases. Recent and anticipated progress for key pipeline programs is noted below:

Cystic Fibrosis

Vertex recently announced plans to initiate Phase 3 studies of the next-in-class, once-daily triple combination of VX-121, tezacaftor and VX-561 in the second half of 2021. Clinical and preclinical data suggest that this triple combination has the potential to provide enhanced benefit for people with CF who have the F508del mutation on at least one allele.
The Phase 3 program will consist of two 48-week trials, which will evaluate the safety and efficacy of the new combination relative to TRIKAFTA in a total of 800 patients. Both studies will measure the regulatory-enabling endpoint of absolute change in ppFEV1, a measure of lung function, that will be analyzed for non-inferiority to TRIKAFTA. Both studies will also assess absolute change from baseline in ppFEV1 and sweat chloride for superiority to TRIKAFTA.

Beta Thalassemia and Sickle Cell Disease

Based on the compelling data generated with CTX001, in April, Vertex and CRISPR Therapeutics announced an amendment to their collaboration for CTX001. In connection with the completion of the transaction in June, Vertex made a $900 million upfront payment to CRISPR.
Data from 22 patients with at least three months of follow-up after CTX001 infusion were presented at EHA (Free EHA Whitepaper) in June and continued to build the profile of a one-time functional cure for patients with transfusion-dependent beta thalassemia (TDT) and severe sickle cell disease (SCD), showing consistent and durable benefit with longer term data from a larger population of patients.
Enrollment and dosing are ongoing in the clinical studies for CTX001 and more than 45 patients have been dosed across the program to date. Vertex anticipates achieving target enrollment in both studies in the third quarter of 2021, with regulatory filings possible in the next 18 to 24 months.
APOL1-mediated Kidney Diseases

Vertex is evaluating the potential of inhibitors of APOL1 function to treat people with APOL1-mediated kidney diseases.
Enrollment is ongoing in a Phase 2 proof-of-concept study designed to evaluate the reduction in proteinuria in people with APOL1-mediated focal segmental glomerulosclerosis (FSGS) following treatment with VX-147.
Data from this study are expected in the second half of 2021.
Pain

NaV1.8 is a genetically and pharmacologically validated novel target for the treatment of pain, and Vertex has previously demonstrated clinical proof-of-concept with a small molecule investigational treatment targeting NaV1.8 in multiple pain indications including acute pain, neuropathic pain and musculoskeletal pain. Vertex’s approach is to selectively inhibit NaV1.8 using small molecules with the objective of creating a new class of medicines that have the potential to provide superior relief of acute pain without the limitations of opioids, including their addictive potential. VX-548 is the most recent molecule to enter clinical development from Vertex’s portfolio of NaV1.8 inhibitors.
Vertex announced in July that the VX-548 Phase 2 acute pain program has been initiated. The proof-of-concept trial for acute pain following bunionectomy surgery is open for enrollment, and the VX-548 trial following abdominoplasty surgery will commence in the coming weeks.
Data from the bunionectomy trial are expected by early 2022.
Type 1 Diabetes (T1D)

Vertex is evaluating a cell therapy designed to replace insulin-producing islet cells in people with T1D. Vertex is pursuing two programs for the transplant of stem cell-derived, fully differentiated, insulin-producing islet cells into patients: 1) transplantation of islet cells alone, using immunosuppression to protect the implanted cells and 2) implantation of the islet cells inside a novel immunoprotective device.
A Phase 1/2 clinical trial for VX-880, the islet cells alone program, is ongoing in people with T1D. The first patient in this study has been dosed, and initial data from this study are expected in 2022.
Alpha-1 Antitrypsin (AAT) Deficiency

Vertex continues to evaluate small molecule correctors of zAAT protein to target the underlying cause of AATD, and thereby address both lung and liver manifestations of the disease.
Vertex plans to advance one or more novel small molecule zAAT correctors into the clinic in 2022.

On July 29, 2021 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported that it will report second quarter 2021 financial results after the close of U.S. financial markets on Thursday, August 5, 2021 (Press release, Kura Oncology, JUL 29, 2021, View Source [SID1234585368]). Kura’s management will host a webcast and conference call at 4:30 p.m. ET / 1:30 p.m. PT that day to discuss the financial results and provide a corporate update.

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