On August 5, 2021 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported business highlights and financial results for the quarter ended June 30, 2021 (Press release, Karyopharm, AUG 5, 2021, View Source [SID1234585902]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Richard Paulson, President and Chief Executive Officer of Karyopharm, commented, "We are encouraged by the commercial performance of XPOVIO during the first half of 2021, which reflected meaningful year-over-year growth, up 21% compared to the first half of 2020, driven by rising confidence and demand from both academic and community-based oncologists. XPOVIO continues to move earlier in the treatment paradigm following U.S. Food and Drug Administration (FDA) approval in the second-line plus treatment setting for multiple myeloma in December 2020. In my first 100 days as CEO, my top priorities have been executional excellence in our multiple myeloma launch and prioritizing and advancing our pipeline. With respect to the launch, we’ve strengthened our organization and execution while solidifying our positioning in the multiple myeloma treatment landscape. XPOVIO is a new and effective modality that can become a standard of care in second-line plus, where utilizing new mechanisms is critical to continue improving patient outcomes. With respect to the pipeline, we have initiated a comprehensive portfolio review and continue to move forward with key new trials."

"Looking ahead to the remainder of 2021, there are several important events and milestones on the horizon. First, we plan to host an investor day in the fourth quarter to outline Karyopharm’s commercial and pipeline priorities and objectives for the upcoming quarters and years. Next, along with continued commercial growth in hematologic cancers, we are expecting top-line data from the Phase 3 SIENDO study in endometrial cancer, also around the end of this year. Endometrial cancer is the most common gynecologic cancer and has the potential to be our first XPOVIO approval in solid tumors. And finally, we expect to initiate or expand several key clinical studies across our pipeline, including in myelodysplastic syndrome, myelofibrosis, multiple myeloma and colorectal cancer," concluded Mr. Paulson.

Second Quarter 2021 & Recent Highlights

XPOVIO Commercial Performance

Achieved U.S. net product revenue for the second quarter of 2021 of $20.2 million and $41.9 million year to date, representing 8% growth compared to the second quarter of 2020 and 21% growth compared to the first half of 2020.
Achieved the following across both multiple myeloma and diffuse large B-cell lymphoma (DLBCL):
Over 7,600 prescriptions filled as of June 30, 2021; and
Added 142 new unique accounts during the second quarter of 2021, an increase of 11% compared to the first quarter of 2021.
Payer coverage remains strong at 97%.
Launched three new strength oral XPOVIO tablets (40mg, 50mg and 60mg), versus only 20mg available previously, to simplify regimens and reduce pill burden for patients.
Intent to prescribe metrics show a rising confidence in physicians’ overall perception of XPOVIO and that physicians are choosing it for earlier lines of treatment; discontinuation rates remain low (approximately 13%).
Strengthened the commercial team with the appointment of Sohanya Cheng, former sales and marketing lead for Kyprolis (carfilzomib) at Amgen, as Head of Sales and Commercial Operations.
Expanded global access to XPOVIO through the conditional approval for XPOVIO plus dexamethasone in the United Kingdom for the treatment of penta-refractory multiple myeloma, and Karyopharm’s partner Antengene securing marketing approval for XPOVIO for the treatment of penta-refractory multiple myeloma and DLBCL in South Korea.
R&D Highlights

Hematologic Malignancies: Karyopharm is actively building its hematologic oncology franchise through several key initiatives, including pursuing NEXPOVIO marketing approval in Europe in the second-line plus treatment setting for multiple myeloma, expanding approved multiple myeloma indications in the U.S. to include combinations with certain approved therapies, and pursuing additional high unmet need indications beyond multiple myeloma, such as myelofibrosis and myelodysplastic syndrome.

European Medicines Agency (EMA) validated the Marketing Authorization Application (MAA) for NEXPOVIO in combination with Velcade (bortezomib) and low-dose dexamethasone for the treatment of multiple myeloma following at least one prior therapy. The MAA will be reviewed by the Committee for Medicinal Products for Human Use (CHMP), which will issue an opinion to the European Commission regarding the potential approval for the expanded indication. Karyopharm expects this review to be completed in the first half of 2022.
Presented positive results for near-term and longer-term multiple myeloma expansion programs at the European Hematology Association (EHA) (Free EHA Whitepaper) 2021 Congress, including:
The arm of the Phase 1b/2 STOMP study evaluating the all oral combination of XPOVIO, Pomalyst (pomalidomide) and dexamethasone (XPd) in previously treated multiple myeloma. Karyopharm remains on track to initiate a randomized Phase 3 study with this combination by the end of 2021.
A subset analysis demonstrating that two STOMP triplet regimens XPOVIO, Kyprolis and dexamethasone (XKd) and XPd achieved high response rates of 67% and 58%, respectively, in multiple myeloma patients with disease refractory to an anti-CD38 monoclonal antibody. These response rates compare favorably to the ~45% response rates seen with other combo regimens.
Commenced dosing in a new Phase 1/2 study evaluating XPOVIO in combination with Jakafi (ruxolitinib) in patients with treatment-naïve myelofibrosis (XPORT-MF-034; NCT04562389).
XPOVIO in Solid Tumors: In 2020, Karyopharm established proof-of-concept for XPOVIO in solid tumors in advanced liposarcoma. The Company is actively pursuing additional solid tumor indications for XPOVIO, either alone or in combination with other agents, including in endometrial cancer, glioblastoma, melanoma, colorectal cancer and non-small cell lung cancer.

Continued enrollment and dosing in the Phase 3 SIENDO study. Remain on track to report top-line results during the fourth quarter of 2021.
Commenced dosing in a new Phase 2 study evaluating XPOVIO in combination with Keytruda (pembrolizumab) in patients with locally advanced or metastatic melanoma (XPORT-MEL-033; NCT04768881).
Corporate & Business Highlights

Richard Paulson, formerly of Ipsen North American and Amgen, named President and Chief Executive Officer.
Received $60 million in expanded royalty agreement with entities managed by HealthCare Royalty Management, LLC (HCR), with up to another $40 million in potential financing available.
Acquired investigational Interleukin-12 (IL-12) program from Neumedicines Inc. for $7.4 million in cash and equity and certain other contingent consideration upon the satisfaction of certain development milestones. Karyopharm is evaluating potential opportunities to combine IL-12 asset with XPOVIO and/or other therapies for cancer and other diseases.
Karyopharm to host an investor day during the fourth quarter of 2021 to outline commercial and pipeline priorities and objectives.
Second Quarter 2021 Financial Results

"Our balance sheet remains strong, and based on our current operating plans, we believe our cash, cash equivalents and investments, together with growing XPOVIO revenues, license revenues and the recent capital secured through our amended agreement with HCR, provide us with a cash runway into mid-2023," said Michael P. Mason, Chief Financial Officer of Karyopharm. "Through steady topline growth, driven by both increased physician adoption as well as adding new patient groups and indications over time, our goal is to become a self-sustaining organization for our stakeholders."

Net product revenue: Net product revenue for the second quarter of 2021 was $20.2 million, compared to $18.6 million for the second quarter of 2020.

License and other revenue: License and other revenue for the second quarter of 2021 was $2.4 million, compared to $14.9 million for the second quarter of 2020. During the three months ended June 30, 2021, Karyopharm recognized $1.0 million pursuant to its license agreement with Anivive Lifesciences, Inc. and $1.4 million of revenue associated with named patient programs. During the three months ended June 30, 2020, Karyopharm recognized $12.7 million pursuant to its license agreement with Antengene Therapeutics Limited and $2.2 million upon reacquisition of the exclusive development and commercial rights from Ono Pharmaceutical Co., Ltd.

Cost of sales: Cost of sales for the second quarter of 2021 were $1.1 million, compared to $0.4 million for the second quarter of 2020. Cost of sales reflects the costs of XPOVIO units sold and third-party royalties on net product revenue.

Research and development (R&D) expenses: R&D expenses for the second quarter of 2021 were $34.0 million, compared to $42.6 million for the second quarter of 2020. The decrease in R&D expenses in the second quarter of 2021 compared to the second quarter of 2020 was primarily attributable to the COVID-19 trial activity in the second quarter of 2020 that did not occur in 2021.

Selling, general and administrative (SG&A) expenses: SG&A expenses for the second quarter of 2021 were $36.5 million, compared to $30.8 million for the second quarter of 2020. The increase in SG&A expenses in the second quarter of 2021 compared to the second quarter of 2020 was due primarily to activities to support the U.S. commercialization of XPOVIO, including the launch of XPOVIO in combination with once-weekly Velcade and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy.

Interest expense: Interest expense for the second quarter of 2021 was $5.0 million, compared to $6.8 million for the second quarter of 2020. The decrease in interest expense was primarily attributable to the decrease in non-cash interest expense related to Karyopharm’s 3.00% senior convertible notes due 2025, as a result of the January 1, 2021 adoption of ASU No. 2020-06, Debt—Debt with Conversion and Other Options and Derivatives and Hedging—Contracts in Entity’s Own Equity. Post adoption, Karyopharm is no longer required to amortize the debt discount to non-cash interest expense, as the debt discount component of $50.6 million has now been reclassified out of equity into the convertible senior notes line on its balance sheet.

Net loss: Karyopharm reported a net loss of $53.6 million, or $0.71 per share, for the second quarter of 2021, compared to a net loss of $46.4 million, or $0.63 per share, for the second quarter of 2020. Net loss included non-cash stock-based compensation expense of $8.1 million and $6.4 million for the second quarters of 2021 and 2020, respectively.

Cash position: Cash, cash equivalents, restricted cash and investments as of June 30, 2021 totaled $239.3 million, compared to $276.7 million as of December 31, 2020.

2021 Financial Outlook

Based on its current operating plans, Karyopharm expects the following for full year 2021:

Non-GAAP R&D and SG&A expenses, excluding stock-based compensation expense, are expected to be in the range of $270 million to $290 million. Karyopharm has not reconciled the full year 2021 outlook for non-GAAP R&D and SG&A expenses to full year 2021 outlook for GAAP R&D and SG&A expenses because Karyopharm cannot reliably predict without unreasonable efforts the timing or amount of the factors that substantially contribute to the projection of stock compensation expense, which is excluded from the full year 2021 outlook for non-GAAP R&D and SG&A expenses.
The Company expects that its existing cash, cash equivalents and investments, together with the revenue it expects to generate from XPOVIO product sales, as well as revenue generated from its license agreements, will be sufficient to fund its planned operations into the middle of 2023.
Non-GAAP Financial Information

Karyopharm uses a non-GAAP financial measure, including R&D and SG&A expenses, to provide operating expense guidance. Non-GAAP R&D and SG&A expenses exclude stock-based compensation expense. Karyopharm believes this non-GAAP financial measure is useful to investors because it provides greater transparency regarding Karyopharm’s operating performance as it excludes non-cash stock compensation expense. This non-GAAP financial measure should not be considered a substitute or an alternative to GAAP R&D and SG&A expenses and should not be considered a measure of Karyopharm’s liquidity. Instead, non-GAAP R&D and SG&A expenses should only be used to supplement an understanding of Karyopharm’s operating results as reported under GAAP.

Conference Call Information

Karyopharm will host a conference call today, Thursday, August 5, 2021, at 8:30 a.m. Eastern Time, to discuss the second quarter 2021 financial results and other company updates. To access the conference call, please dial (888) 437-3179 (local) or (862) 298-0702 (international) at least 10 minutes prior to the start time and ask to be joined into the Karyopharm Therapeutics call. A live audio webcast of the call will be available under "Events & Presentations" in the Investor section of the Company’s website, View Source An archived webcast will be available on the Company’s website approximately two hours after the event.

About XPOVIO (selinexor)

XPOVIO is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). XPOVIO blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion. Karyopharm received accelerated U.S. Food and Drug Administration (FDA) approval of XPOVIO in July 2019 in combination with dexamethasone for the treatment of adult patients with relapsed refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. NEXPOVIO (selinexor) has also been granted conditional marketing authorization for adult patients with heavily pretreated multiple myeloma by the European Commission. Karyopharm’s supplemental New Drug Application (sNDA) requesting an expansion of its indication to include the treatment for patients with multiple myeloma after at least one prior therapy was approved by the FDA on December 18, 2020. In June 2020, Karyopharm received accelerated FDA approval of XPOVIO for its second indication in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including as a potential backbone therapy in combination with approved myeloma therapies (STOMP) and in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm’s clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

For more information about Karyopharm’s products or clinical trials, please contact the Medical Information department at:

Tel: +1 (888) 209-9326
Email: [email protected]

XPOVIO (selinexor) is a prescription medicine approved:

In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (XVd).
In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti–CD38 monoclonal antibody (Xd).
For the treatment of adult patients with relapsed or refractory diffuse large B–cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
SELECT IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care.
Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony–stimulating factors.
Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care.
Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care.
Serious Infection: Monitor for infection and treat promptly.
Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes.
Embryo–Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception.
Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract.
Adverse Reactions

The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3–4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%.
The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.
The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3–4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal adverse reactions was infection (4.5% of patients). Serious adverse reactions occurred in 46% of patients; the most frequent serious adverse reaction was infection (21% of patients). Discontinuation due to adverse reactions occurred in 17% of patients.
Use In Specific Populations

Lactation: Advise not to breastfeed.

On August 5, 2021 Bicycle Therapeutics plc (NASDAQ: BCYC), a biotechnology company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, reported financial results for the second quarter ended June 30, 2021 and provided recent corporate updates (Press release, Bicycle Therapeutics, AUG 5, 2021, View Source [SID1234585901]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We have made significant progress executing on our ongoing company-sponsored clinical programs over the first half of the year and, looking forward, intend to announce interim clinical data from the Phase I portion of our Phase I/II clinical trials of BT5528 and BT8009, along with the expected Phase I/II BT7840 trial initiation, in the second half of the year," said Kevin Lee, Ph.D., Chief Executive Officer of Bicycle Therapeutics. "Additionally, we believe our recent license and collaboration agreement with Ionis provides further validation for our contention that Bicycles have the potential to become a leading technology for the development of precision medicines. We remain well-funded and look forward to announcing multiple upcoming key clinical milestones in the second half of the year."

Second Quarter 2021 and Recent Highlights

Entered into an Exclusive License and Collaboration Agreement with Ionis Pharmaceuticals to Develop Targeted Oligonucleotide Therapeutics. In July 2021, Ionis exercised its option under the terms of a December 2020 evaluation and option agreement and entered into an exclusive worldwide license and collaboration agreement for tissue-targeted delivery of oligonucleotide therapeutics using Bicycles with high affinity to the transferrin receptor (TfR1). Bicycle received $45 million upfront, which included a license fee, an option fee, and an $11 million equity investment. Bicycle is also eligible to receive development, regulatory and commercial milestone payments and royalties for programs developed under the collaboration.
Continued to Strengthen the Balance Sheet in the Second Quarter of 2021. The Company recognized gross proceeds from Bicycle’s at-the-market (ATM) offering program during the second quarter of 2021 totaling $14.4 million as of June 30, 2021, with an additional $30.8 million received in July 2021. Cash as of June 30, 2021 does not include $42 million of proceeds from the Ionis license and collaboration agreement or net proceeds from the ATM offering program received subsequent to the end of the second quarter of 2021.
Financial Results

Cash was $198.7 million as of June 30, 2021, compared to $136.0 million as of December 31, 2020. The increase in cash during the first six months of 2021 is primarily due to net proceeds of $72.8 million from the ATM offering program and net proceeds of $15.0 million from the debt facility with Hercules Capital, Inc., offset by cash used in operating activities. Cash of $198.7 million at June 30, 2021 is expected to provide financial runway through multiple clinical milestones and into 2024.
Research and development expenses were $11.7 million for the three months ended June 30, 2021, compared to $8.0 million for the three months ended June 30, 2020. The increase in expense of $3.7 million for the three months ended June 30, 2021 as compared to the same period in the prior year was primarily due to increased clinical program expenses for BT8009, a second-generation Bicycle Toxin Conjugate (BTC) targeting Nectin-4, increased other unallocated discovery and platform related expenses due to the timing of development activities, and increased personnel-related expenses, including $0.6 million of incremental non-cash share-based compensation expense.
General and administrative expenses were $7.3 million for the three months ended June 30, 2021, compared to $6.2 million for the three months ended June 30, 2020. The increase of $1.1 million for the three months ended June 30, 2021 as compared to the same period in the prior year was primarily due to an increase in personnel-related costs, including $0.7 million of incremental non-cash share-based compensation expense, offset by a decrease in professional and consulting fees.
Net loss was $17.9 million, or $(0.74) basic and diluted net loss per share, for the three months ended June 30, 2021, compared to net loss of $12.1 million, or $(0.67) basic and diluted net loss per share for three months ended June 30, 2020.

On August 5, 2021 Cardinal Health (NYSE: CAH) reported that fourth-quarter fiscal 2021 revenue increased 16% to $42.6 billion (Press release, Cardinal Health, AUG 5, 2021, View Source [SID1234585900]). This increase includes the favorable prior year comparison from reduced pharmaceutical demand related to COVID-19. Fiscal year 2021 revenues were $162.5 billion, a 6% increase from fiscal year 2020.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Cardinal Health, Inc. is a global, integrated healthcare services and products company, providing customized solutions for hospitals, healthcare systems, pharmacies, ambulatory surgery centers, clinical laboratories and physician offices worldwide. (PRNewsfoto/Cardinal Health)

Both GAAP and Non-GAAP operating earnings during the fourth quarter and fiscal year 2021 were adversely impacted by a $197 million COVID-19-related inventory reserve related to certain Personal Protective Equipment (PPE) in the Medical segment. Fourth-quarter and full year GAAP diluted earnings per share (EPS) were also negatively impacted by $149 million and $1.17 billion pre-tax charges, respectively, related to opioid lawsuits brought by states and local governmental entities.

Fourth-quarter GAAP operating earnings decreased 40% to $162 million and GAAP diluted EPS decreased to $0.40. Non-GAAP operating earnings decreased 28% to $320 million and Non-GAAP diluted EPS decreased 26% to $0.77 in the quarter.

Fiscal year 2021 GAAP operating earnings were $472 million and non-GAAP operating earnings decreased 5% to $2.3 billion. GAAP diluted EPS for fiscal year 2021 were $2.08, while non-GAAP diluted EPS were $5.57.

"We’re disappointed with our fourth quarter results. Throughout the past year we have been taking action to drive performance, and we will continue to move forward with urgency," said Mike Kaufmann, CEO of Cardinal Health. "For example, we divested the Cordis business, extended our Red Oak Sourcing agreement with CVS Health, identified $250 million of additional cost savings opportunities and made important leadership changes. With the actions we’ve taken to date and our plans for fiscal year 2022, we feel confident in our strategy, and are encouraged by the tailwinds behind our growth areas and strong cash flow generation."

COVID-19
The COVID-19 pandemic adversely affected fiscal year 2021 results. The company estimates that COVID-19 had a total net negative impact to both GAAP and non-GAAP operating earnings of approximately $300 million in fiscal year 2021, or approximately $200 million on a year-over-year basis.

Fourth-quarter revenue for the Pharmaceutical segment increased 15% to $38.3 billion driven primarily by sales growth from large Pharmaceutical Distribution and Specialty Solutions customers. This increase also includes the favorable prior year comparison from reduced pharmaceutical demand related to COVID-19.

Pharmaceutical segment profit was flat at $358 million in the fourth quarter. This reflects COVID-19-related volume recovery in the Nuclear and Precision Health Solutions business, offset by the adverse impact of Pharmaceutical Distribution customer contract renewals.

Fourth-quarter revenue for the Medical segment increased 23% to $4.2 billion, driven by a net positive impact from COVID-19 on products and distribution. This increase was primarily due to a recovery in elective procedure volumes and the positive pricing impact of PPE.

Medical segment loss of $63 million in the fourth quarter was due to an adverse impact from COVID-19. This was primarily due to an inventory reserve on certain PPE products, partially offset by a recovery in elective procedure volumes. Additionally, benefits from cost savings initiatives were offset by elevated supply chain costs.

Tax rate
The GAAP effective tax rates for the fourth quarter of fiscal year 2021, fiscal year 2021 and fiscal year 2020 included net tax benefits related to the treatment of the tax impacts of the opioid litigation charges. Included in the GAAP effective tax rate for fiscal 2021 was a benefit from the net operating loss carryback primarily related to a self-insurance pre-tax loss.

Fiscal year 2022 non-GAAP EPS guidance reflects a net tailwind related to COVID-19 of approximately $200 million compared to the prior year. Additionally, the company expects incremental investments of approximately $120 million in technology enhancements to drive growth and efficiencies, as well as an approximate $80 million negative impact to operating earnings due to the Cordis divestiture. Fiscal year 2022 non-GAAP EPS guidance reflects share repurchases in the range of $500 million to $1.0 billion.

The company does not provide forward-looking guidance on a GAAP basis as certain financial information, the probable significance of which cannot be determined, is not available and cannot be reasonably estimated. See "Use of Non-GAAP Measures" following the attached schedules for additional explanation.

Recent highlights

Cardinal Health amended its Red Oak Sourcing agreement with CVS Health to extend the term of the generic pharmaceutical sourcing venture through June 2029.
Cardinal Health announced the completion of the previously announced sale of Cardinal Health’s Cordis business to Hellman & Friedman for a sale price of approximately $1 billion.
Cardinal Health, along with pharmaceutical distribution peers, announced that they have negotiated a comprehensive proposed settlement agreement which, if all conditions are satisfied, would result in the settlement of a substantial majority of opioid lawsuits filed by state and local governmental entities.
Cardinal Health Board of Directors approved a quarterly dividend of $0.4908 per share. The dividend will be payable on October 15, 2021 to shareholders of record at the close of business on October 1, 2021.
Cardinal Health has been named one of the 2021 Best Companies for Multicultural Women by Seramount (formerly Working Mother Media), an honor recognizing companies that create and use best practices in hiring, retaining and promoting multicultural women in the United States.
Upcoming webcasted investor events

Morgan Stanley 19th Annual Global Healthcare Conference at 8:00 a.m. Eastern, September 14, 2021
Webcast
Cardinal Health will host a webcast today at 8:30 a.m. Eastern to discuss fourth-quarter results. To access the webcast and corresponding slide presentation, go to the Investor Relations page at ir.cardinalhealth.com. No access code is required.

Presentation slides and a webcast replay will be available until August 5, 2022.

On August 5, 2021 Jounce Therapeutics, Inc. (NASDAQ: JNCE), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers, reported financial results for the second quarter ended June 30, 2021 and provided a corporate update (Press release, Jounce Therapeutics, AUG 5, 2021, View Source [SID1234585899]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"I am very pleased with the progress Jounce has made this quarter as we continued to advance our two proof of concept studies, INNATE and SELECT, achieved IND clearance on our fourth internally discovered program and expanded our discovery programs to include additional LILRB family members. Our team has made important and rapid progress in our INNATE study with the announcement today of monotherapy dose escalation enrollment completion and target dose selection. We look forward to beginning the next stages of the trial in third quarter of this year," said Richard Murray, Ph.D., chief executive officer and president of Jounce Therapeutics. "We remain steadfast in our commitment to discover and develop novel IO therapies to meet the growing unmet medical need experienced in cancer patients, particularly in the area of PD-(L)1 inhibitor resistance. We believe our focus on translational science, biomarker approaches, and targeting new immune mechanisms leads us closer to bringing the right immunotherapies to the right patients."

Pipeline Update:

JTX-8064 (LILRB2 / ILT4)

Completed enrollment in monotherapy dose escalation portion of INNATE: Jounce announces today that the monotherapy dose escalation portion of the Phase 1 trial of JTX-8064 is complete. The monotherapy dose escalation included seven doses ranging from 50 mg to the highest planned dose of 1200 mg. To date, JTX-8064 has been well-tolerated with no dose limiting toxicities.
Identified target dose for next stages of INNATE: Jounce announces today the selection of its target dose of 700 mg. The selected target dose was based on a combination of safety, pharmacokinetic, and receptor occupancy data in the first three-week cycle. During the third quarter of 2021, Jounce expects to open eight expansion cohorts for enrollment, one with JTX-8064 monotherapy at its target dose and seven with JTX-8064 in combination with pimivalimab.
Presented trial in progress posters at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 Annual Meeting: In June 2021, Jounce presented a trial in progress poster at the ASCO (Free ASCO Whitepaper) Annual Meeting on INNATE. The poster included the study design and the rationale for indications chosen for the expansion cohorts.
Vopratelimab (ICOS) and Pimivalimab (PD-1)

Continued enrollment in Phase 2 SELECT trial of vopratelimab: Enrollment continues in SELECT, a randomized Phase 2 trial to evaluate vopratelimab in combination with pimivalimab versus pimivalimab alone in immunotherapy naïve, TISvopra biomarker-selected, second line non-small cell lung cancer (NSCLC) patients. The SELECT trial also aims to provide additional important single agent data for pimivalimab in a new biomarker selection paradigm. Jounce is on track to report data from the SELECT trial in 2022.
Presented trial in progress poster at the ASCO (Free ASCO Whitepaper) 2021 Annual Meeting: In June 2021, Jounce presented a trial in progress poster at the ASCO (Free ASCO Whitepaper) Annual Meeting on SELECT. The poster described the study design, TISvopra biomarker, and patient selection strategy of the SELECT trial.
JTX-1811 (CCR8)

Clearance of IND triggering first milestone under Gilead license agreement: In June 2021, Jounce received clearance from the U.S. Food and Drug Administration (FDA) of an investigational new drug (IND) application for JTX-1811, a potential first-in-class antibody designed to bind to CCR8 and selectively deplete immunosuppressive tumor-infiltrating T regulatory cells. The IND clearance triggered a $25.0 million milestone payment to Jounce which was received in July 2021. Gilead now has sole rights to develop and commercialize the JTX-1811 program, which will be referred to as GS-1811 in their pipeline.
Discovery Pipeline

Announced new discovery program targets: Jounce continues to invest in and advance its growing immuno-oncology pipeline. The broad discovery pipeline includes multiple programs targeting diverse immune cell types and PD-(L)1 inhibitor resistance mechanisms. Jounce is rapidly advancing two additional LILRB family programs through discovery, one targeting LILRB1 and the other targeting LILRB4. With the goal of submitting a new IND every 12 to 18 months, Jounce expects at least one of its next development candidates to target the LILRB family of receptors.
Second Quarter 2021 Financial Results:

Cash position: As of June 30, 2021, cash, cash equivalents and investments were $246.1 million, compared to $213.2 million as of December 31, 2020. The increase was primarily due to receipt of $90.9 million in net proceeds from the follow-on public offering and sales under Jounce’s at-the-market offering program completed during the period, offset by operating expenses incurred. This amount excludes the $25.0 million milestone Jounce received from Gilead in July 2021.
License and collaboration revenue: Jounce recognized $25.4 million of license and collaboration revenue during the second quarter of 2021. License and collaboration revenue recognized during the period was related to milestone achievement and research and transition services performed under the license agreement with Gilead. No revenue was recognized for the same period in 2020.
Research and development expenses: Research and development expenses were $22.1 million for the second quarter of 2021, compared to $21.0 million for the same period in 2020. The increase in research and development expenses was primarily due to increased manufacturing activities performed for Jounce’s development programs and increased clinical and regulatory spend on JTX-8064 offset by decreased spend on vopratelimab.
General and administrative expenses: General and administrative expenses were $7.3 million for the second quarter of 2021, compared to $7.2 million for the same period in 2020. The increase in general and administrative expenses was primarily due to increased insurance expense.
Net loss: Net loss was $4.0 million for the second quarter of 2021, resulting in basic and diluted net loss per share of $0.08. Net loss was $28.0 million for the same period in 2020, resulting in a basic and diluted net loss per share of $0.82. The decrease in net loss and net loss per share was attributable to revenue recognized in the second quarter of 2021.
Financial Guidance:

Based on its current operating and development plans, Jounce continues to expect gross cash burn on operating expenses and capital expenditures for the full year 2021 to be approximately $95.0 million to $110.0 million.

Given the strength of its balance sheet, Jounce expects its existing cash, cash equivalents and investments to be sufficient to enable the funding of its operating expenses and capital expenditure requirements through the third quarter of 2023.

Conference Call and Webcast Information:

Jounce Therapeutics will host a live conference call and webcast today at 8:00 a.m. ET. To access the conference call, please dial (866) 916-3380 (domestic) or (210) 874-7772 (international) and refer to conference ID 4291658. The live webcast can be accessed under "Events & Presentations" in the Investors and Media section of Jounce’s website at www.jouncetx.com. The webcast will be archived and made available for replay on Jounce’s website approximately two hours after the call and will be available for 30 days.

On August 5, 2021 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported financial results for the second quarter of 2021 and provided a business update (Press release, Regeneron, AUG 5, 2021, View Source [SID1234585898]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Regeneron had outstanding performance in the second quarter during which we delivered to the U.S. government the entire order for our COVID-19 antibody cocktail and recognized record global sales from our EYLEA and Dupixent franchises," said Leonard S. Schleifer, M.D., Ph.D., President and Chief Executive Officer of Regeneron. "We continue to advance Dupixent’s potential to help new patient groups, with recent positive Phase 3 data in chronic spontaneous urticaria and additional late-stage read-outs expected later this year in prurigo nodularis, eosinophilic esophagitis, and pediatric atopic dermatitis. With today’s positive Phase 3 results in combination with chemotherapy in non-small cell lung cancer, Libtayo yet again demonstrates its potential to be a leading checkpoint inhibitor. We also progressed our genetics medicines platform, with landmark clinical data alongside our collaborator Intellia using a CRISPR therapeutic and the discovery of a promising new obesity target from the Regeneron Genetics Center."

"Regeneron performed exceptionally well in the second quarter with the core business on a strong growth trajectory as we invest in our diverse and differentiated pipeline for long-term and sustainable growth," said Robert E. Landry, Executive Vice President, Finance and Chief Financial Officer of Regeneron.

Business Highlights

Key Pipeline Progress

Regeneron has approximately 30 product candidates in clinical development, including six marketed products for which it is investigating additional indications. Updates from the clinical pipeline include:

EYLEA (aflibercept) Injection

Enrollment in the Phase 3 studies for high-dose formulation in diabetic macular edema (DME) and neovascular age-related macular degeneration (wet AMD) was completed.
Enrollment in the Phase 3 study for retinopathy of prematurity (ROP) was also completed.
Dupixent (dupilumab)

The Company and Sanofi announced a Phase 3 trial in patients with moderate-to-severe chronic spontaneous urticaria (CSU) met its primary and all key secondary endpoints at 24 weeks. The trial showed that adding Dupixent to standard-of-care antihistamines significantly reduced itch and hives for biologic-naive patients, compared to antihistamines alone in the first of two trials of this clinical program.
In June 2021, the U.S. Food and Drug Administration (FDA) approved a 200 mg single-dose pre-filled pen for Dupixent.
REGEN-COVTM (casirivimab and imdevimab)(2), a dual antibody cocktail to SARS-CoV-2 virus

In the second quarter of 2021, the Company fulfilled its second agreement with the U.S. government to manufacture and deliver 1.25 million doses of REGEN-COV at the lowest treatment dose authorized by the FDA, and recognized $2.59 billion of REGEN-COV sales.
In June 2021, the FDA updated the REGEN-COV EUA by lowering the dose to 1,200 mg and permitting administration by subcutaneous injection when intravenous infusion is not feasible.
In July 2021, based on positive Phase 3 data announced in April 2021 which were recently published in the New England Journal of Medicine, the FDA also expanded the EUA to include post-exposure prophylaxis in people at high risk for progression to severe COVID-19, who are not fully vaccinated or are not expected to mount an adequate response to vaccination, and who have been exposed to a SARS-CoV-2 infected individual or are at high risk of exposure to an infected individual because of infection occurring in the same institutional setting (such as in nursing homes or prisons). For people who are not expected to mount an adequate immune response to vaccination, REGEN-COV can also now be administered monthly for the duration of ongoing exposure to SARS-CoV-2.
In July 2021, Japan’s Ministry of Health, Labour and Welfare (MHLW) approved the casirivimab and imdevimab antibody cocktail to treat patients with mild to moderate COVID-19, making Japan the first country to grant a full approval for the antibody cocktail.
Positive results were announced from the Phase 3 UK-based RECOVERY trial in hospitalized COVID-19 patients, demonstrating that adding REGEN-COV to usual care reduced the risk of death by 20% in seronegative patients (patients who had not mounted a natural antibody response on their own against SARS-CoV-2), compared to seronegative patients receiving usual care alone. The Company has requested that the EUA be further expanded to include appropriate hospitalized patients.
Libtayo (cemiplimab)

In June 2021, the European Commission (EC) approved Libtayo for the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC).
In June 2021, the EC also approved Libtayo for the treatment of metastatic or locally advanced basal cell carcinoma (BCC).
In August 2021, the Company and Sanofi announced that the Phase 3 trial of Libtayo in combination with platinum-doublet chemotherapy was stopped early after meeting its overall survival primary endpoint in patients with advanced NSCLC. These data are planned to form the basis of regulatory submissions in the United States and European Union (EU).
Odronextamab, a CD20xCD3 bispecific antibody

The Company is resuming enrollment of patients with follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL), following amendment of trial protocols and the FDA’s lifting of the partial clinical hold, in its monotherapy trials of odronextamab.
Fianlimab, an antibody to LAG-3

Positive data from the Phase 1 trial in combination with Libtayo in advanced melanoma were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting; the Company intends to initiate a Phase 3 study in 2022.
REGN1908-1909, a multi-antibody therapy to Fel d 1

The Company initiated a Phase 3 study in cat allergic asthmatics.
Genetics Medicines

Intellia Therapeutics, Inc. and the Company announced positive interim data from the Phase 1 study of NTLA-2001, a CRISPR/Cas9 therapeutic for TTR gene knockout in people living with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). These are the first-ever clinical data supporting safety and efficacy of in vivo CRISPR genome editing in humans and provide proof of concept for the ongoing multi-target collaboration between the companies.
The Regeneron Genetics Center published their discovery of GPR75 gene mutations that protect against obesity. This target is the focus of a small molecule collaboration agreement with AstraZeneca announced in July 2021, under which the companies will equally share research and development costs and any potential future profits.
Corporate Updates

The Company intends to invest approximately $1.8 billion over six years to expand its research, preclinical manufacturing, and support facilities at the Company’s Tarrytown, New York campus.

Second Quarter 2021 Financial Results

Revenues

Total revenues increased by 163% to $5.139 billion in the second quarter of 2021, compared to $1.952 billion in the second quarter of 2020. Total revenues excluding (i) REGEN-COV (casirivimab and imdevimab) net product sales in the United States and (ii) the Company’s share of gross profits in connection with Roche’s sales of casirivimab and imdevimab outside the United States, increased by 22% to $2.379 billion in the second quarter of 2021, compared to the second quarter of 2020(1).

Net product sales of EYLEA in the United States increased in the second quarter of 2021, compared to the second quarter of 2020, primarily due to higher sales volume as well as a favorable comparison given the adverse impact of the COVID-19 pandemic on U.S. EYLEA demand during the second quarter of 2020.

The Company fulfilled its second agreement with the U.S. government and delivered 1.25 million doses of REGEN-COV. Other than $34 million of expected REGEN-COV net product sales in the third quarter of 2021 related to this agreement, the Company does not anticipate recording any additional net product sales of REGEN-COV in the United States during the third quarter of 2021. U.S. net product sales of REGEN-COV in the fourth quarter of 2021 will be dependent upon acceleration of COVID-19 cases and related drug utilization.

Total revenues also include collaboration revenues(3) of $955 million in the second quarter of 2021, compared to $513 million in the second quarter of 2020. Sanofi collaboration revenue increased primarily due to the Company’s share of profits from commercialization of antibodies, which were $328 million in the second quarter of 2021, compared to $172 million in the second quarter of 2020. The change in the Company’s share of profits from commercialization of antibodies was driven by higher Dupixent profits. In the second quarter of 2021, the Company also recorded Roche collaboration revenue of $168 million in connection with the Company’s share of gross profits from Roche’s sales of the casirivimab and imdevimab antibody cocktail outside the United States.

Refer to Table 4 for a summary of collaboration revenue.

Other revenue decreased in the second quarter of 2021, compared to the second quarter of 2020, primarily due to lower amounts recognized in connection with the Company’s agreements with the Biomedical Advanced Research Development Authority (BARDA) related to funding of certain development activities for antibodies for the treatment of COVID-19.

GAAP R&D expenses in the second quarter of 2020 included $85 million in up-front payments in connection with the collaboration agreement with Intellia. The decrease in GAAP R&D expenses in the second quarter of 2021 was offset primarily by higher costs incurred in connection with development activities related to REGEN-COV, which also drove the increase in non-GAAP R&D expenses.
The increase in GAAP and non-GAAP SG&A expenses in the second quarter of 2021 was primarily due to higher headcount-related costs, an increase in commercialization-related expenses for EYLEA and Libtayo, and costs associated with educational campaigns related to COVID-19.
The increase in COGS in the second quarter of 2021 was primarily due to the recognition of manufacturing costs in connection with product sales of REGEN-COV in the United States. In addition, the Company recognized higher inventory write-offs and reserves in the second quarter of 2021, compared to the second quarter of 2020.
Other operating (income) expense, net, includes recognition of a portion of amounts previously deferred in connection with up-front and development milestone payments, as applicable, received in connection with the Company’s collaborative arrangements.
Other Financial Information

GAAP other income (expense), net, includes the recognition of net unrealized and realized gains on equity securities of $409 million in the second quarter of 2021, compared to $228 million in the second quarter of 2020.

In the second quarter of 2021, the Company’s GAAP effective tax rate was 17.4%, compared to 2.4% in the second quarter of 2020. The increase in the second quarter 2021 GAAP effective tax rate, compared to the second quarter of 2020, was primarily due to the significant positive impact of stock-based compensation in the second quarter of 2020. In the second quarter of 2021, the non-GAAP effective tax rate was 17.0%, compared to 0.9% in the second quarter of 2020.

GAAP net income per diluted share was $27.97 in the second quarter of 2021, compared to GAAP net income per diluted share of $7.61 in the second quarter of 2020. Non-GAAP net income per diluted share was $25.80 in the second quarter of 2021, compared to non-GAAP net income per diluted share of $7.16 in the second quarter of 2020. A reconciliation of the Company’s GAAP to non-GAAP results is included in Table 3 of this press release.

Net cash provided by operating activities in the first half of 2021 was $1.295 billion, compared to $1.641 billion in the first half of 2020, resulting in $1.031 billion in free cash flow for the first half of 2021, compared to $1.341 billion for the first half of 2020. The Company expects a significant increase in free cash flow in the third quarter of 2021 as the Company collected all amounts due from the U.S. government in connection with second quarter 2021 REGEN-COV sales in July 2021.

2021 Financial Guidance(4)

Conference Call Information

Regeneron will host a conference call and simultaneous webcast to discuss its second quarter 2021 financial and operating results on Thursday, August 5, 2021, at 8:30 AM Eastern Time. To access this call, dial (888) 660-6127 (U.S.) or (973) 890-8355 (International), conference ID 9098036. A link to the webcast may be accessed from the "Investors and Media" page of Regeneron’s website at www.regeneron.com. A replay of the conference call and webcast will be archived on the Company’s website and will be available for at least 30 days.