On July 28, 2021 Myovant Sciences (NYSE: MYOV), a healthcare company focused on redefining care for women and for men, reported corporate updates and financial results for the first quarter of fiscal year 2021 (Press release, Myovant Sciences, JUL 28, 2021, View Source [SID1234585259]).

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"I am pleased with the significant progress Myovant has made toward delivering on our mission of redefining care for women and for men. MYFEMBREE was approved by the FDA in May for women with uterine fibroids and was launched by Myovant and Pfizer in mid-June. We are encouraged by our early progress and are excited to be bringing this important new treatment option to the millions of women suffering from the symptoms of uterine fibroids. In July, we submitted to the FDA a supplemental New Drug Application seeking to extend approval of MYFEMBREE to include women with endometriosis. Finally, RYEQO was approved in Europe as the first and only long-term, once-daily oral treatment for uterine fibroids. We look forward to RYEQO’s launch later this year, to be executed by Gedeon Richter," said David Marek, Chief Executive Officer of Myovant Sciences, Inc.

Mr. Marek added, "ORGOVYX launch momentum continued to accelerate in first fiscal quarter 2021 with net product revenues of $10.5 million, demonstrating substantial growth compared to the previous quarter. This performance reflects the overwhelmingly positive feedback we have received from patients and clinicians regarding the impact ORGOVYX has had on the advanced prostate cancer treatment experience. Providing patients and prescribers with an oral medication that is able to rapidly and profoundly reduce testosterone levels without an initial hormonal surge has positioned ORGOVYX to potentially become the new standard of care androgen deprivation therapy over time."

First Fiscal Quarter 2021 and Recent Corporate Updates

ORGOVYX (relugolix 120 mg)

First fiscal quarter 2021 net product revenues for ORGOVYX in the U.S. were $10.5 million, driven by increased prescriber demand.
Approximately 1,150 treatment centers have prescribed ORGOVYX to over 4,500 patients on free and commercial drug, estimated through June 30, 2021. The number of estimated patients initiating ORGOVYX therapy has steadily increased in each successive month since launch.
As of July 1, 2021, Myovant achieved 63% commercial coverage and 78% Medicare Part D coverage for ORGOVYX. Myovant continues to engage in negotiations with payors yet to make 2021 coverage decisions and now expects to achieve broad coverage before its original calendar year-end 2021 goal.
MYFEMBREE (relugolix 40 mg, estradiol 1.0 mg, and norethindrone acetate 0.5 mg)

On May 26, 2021, MYFEMBREE was approved by the U.S. Food and Drug Administration (FDA) as the first and only once-daily oral treatment for the management of heavy menstrual bleeding associated with uterine fibroids.
The FDA approval of MYFEMBREE triggered a $100.0 million regulatory milestone payment from Pfizer, which Myovant received in July 2021 (Myovant’s second fiscal quarter 2021).
In mid-June 2021, Myovant and Pfizer launched MYFEMBREE in the U.S. First fiscal quarter 2021 net product revenues for MYFEMBREE in the U.S. were $1.1 million, reflecting initial inventory stocking by distributors upon MYFEMBREE product availability.
As of July 1, 2021, 37% of commercial lives were eligible for pre-review coverage for MYFEMBREE. Myovant continues to engage in coverage negotiations with key commercial payors and remains on track to achieve its goal of broad coverage within one year of launch.
On July 6, 2021, Myovant submitted a supplemental New Drug Application (sNDA) to the FDA for once-daily MYFEMBREE for the management of moderate to severe pain associated with endometriosis. In April and June 2020 and January 2021, Myovant reported positive results from the two replicate Phase 3 SPIRIT studies and the SPIRIT long-term extension study.
On June 15, 2021, the United States Patent and Trademark Office (USPTO) granted U.S. Patent. No. 11,033,551 to Myovant. This patent covers the unique and innovative method of treating patients for heavy menstrual bleeding associated with uterine fibroids with MYFEMBREE. This patent will expire in September of 2037 and is listed in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations (the "Orange Book"). This patent term matches that of two methods patents (U.S. Patent. Nos. 10,786,501 and 10,449,191) previously granted by the USPTO for ORGOVYX that cover methods of treating advanced prostate cancer with relugolix.
On May 18, 2021, the FDA informed Myovant that they placed a partial clinical hold on the Phase 3 SERENE study evaluating MYFEMBREE for the prevention of pregnancy, pending certain study protocol modifications. In July 2021, Myovant provided to the FDA an amended study protocol for the SERENE study. Following Myovant’s discussions with the FDA, Myovant expects the partial clinical hold to be lifted in August 2021.
RYEQO (relugolix 40 mg, estradiol 1.0 mg, and norethindrone acetate 0.5 mg)

On July 16, 2021, the European Commission (EC) approved RYEQO for the treatment of moderate to severe symptoms of uterine fibroids in adult women of reproductive age. RYEQO is the first and only long-term, once-daily oral treatment for uterine fibroids in Europe and has no limitation on its duration of use. The approval was based on safety and efficacy data from the Phase 3 LIBERTY program, which consisted of two replicate, 24-week, multinational clinical studies (LIBERTY 1 and LIBERTY 2), a one-year extension study, and supportive bone mineral density data from a randomized withdrawal study. The commercial launch of RYEQO is expected to begin in the second half of calendar year 2021 and will be executed by Gedeon Richter (Richter), Myovant’s commercialization partner for RYEQO in Europe and certain other international markets.
The approval of RYEQO for the uterine fibroids indication by the EC triggered a $15.0 million regulatory milestone payment due from Richter, which Myovant expects to receive and record as Richter license and milestone revenue in its second fiscal quarter of 2021. In addition to tiered milestones upon reaching certain net sales thresholds, Myovant is also eligible to receive tiered royalties on net sales.
Pfizer Collaboration

In July 2021, Myovant and Pfizer agreed to extend the timeline for Pfizer’s decision to exercise its exclusive option to develop and commercialize relugolix in oncology outside of the U.S. and Canada, excluding certain Asian countries (the "Pfizer Territory"), through the end of October 2021.
Expected Upcoming Milestones

Pfizer’s decision regarding its exclusive option to acquire development and commercialization rights to relugolix in oncology in the Pfizer Territory is expected by the end of October 2021. If Pfizer exercises this option, Myovant will receive a $50.0 million payment and will be eligible to receive double-digit royalties on net sales in the Pfizer Territory.
Commercial launch of RYEQO in Europe is expected to begin in the second half of calendar year 2021, to be executed by Richter.
Marketing Authorization Application (MAA) submission to the European Medicines Agency for RYEQO for the treatment of women with endometriosis-associated pain is expected in the second half of calendar year 2021. Richter will be the MAA sponsor.
FDA submission of the Phase 3 LIBERTY randomized withdrawal study results for MYFEMBREE in women with uterine fibroids is expected by the end of calendar year 2021.
EC decision on the advanced prostate cancer MAA is expected in calendar year 2022.
First Fiscal Quarter 2021 Financial Summary

Total revenues for the three months ended June 30, 2021 and 2020 were $41.1 million and $33.3 million, respectively.

Product revenue, net from sales of ORGOVYX and MYFEMBREE in the U.S. for the three months ended June 30, 2021 were $10.5 million and $1.1 million, respectively. There were no such revenues recorded in the comparable prior year period.
Pfizer collaboration revenue for the three months ended June 30, 2021 was $29.5 million, reflecting the partial recognition of the upfront payment Myovant received from Pfizer in December 2020 and of the regulatory milestone payment that was triggered upon the FDA approval of MYFEMBREE for the management of heavy menstrual bleeding associated with uterine fibroids on May 26, 2021. There were no such revenues recorded in the comparable prior year period.
Richter license and milestone revenue for the three months ended June 30, 2020 was $33.3 million, reflecting the partial recognition of the upfront payment Myovant received from Richter in March 2020 and the regulatory milestone payment Myovant received from Richter in April 2020. There were no such revenues in the three months ended June 30, 2021.
Cost of product revenue for the three months ended June 30, 2021 was $1.0 million related to the cost of goods sold and royalty expense payable to Takeda pursuant to the Takeda License Agreement. There were no such amounts recognized in the comparable prior year period.

Collaboration expense to Pfizer for the three months ended June 30, 2021, was $5.3 million, reflecting Pfizer’s 50% share of net profits from sales of ORGOVYX and MYFEMBREE in the U.S., pursuant to the Pfizer Collaboration and License Agreement. There were no such amounts recognized in the comparable prior year period.

Research and development (R&D) expenses for the three months ended June 30, 2021, were $30.9 million compared to $44.2 million for the comparable prior year period. The decrease in R&D expenses reflects cost share reimbursements from Pfizer for certain R&D expenses and a reduction in clinical study costs as a result of the completion and wind down of Myovant’s Phase 3 LIBERTY, HERO, and SPIRIT studies. The decrease also reflects lower regulatory expenses during the three months ended June 30, 2021, as the prior year period included submission fees for Myovant’s New Drug Applications for ORGOVYX for advanced prostate cancer and MYFEMBREE for the uterine fibroids indication. This decrease was partially offset by an increase in medical affairs personnel expenses to support the U.S. commercial launches of ORGOVYX and MYFEMBREE.

Selling, general and administrative (SG&A) expenses for the three months ended June 30, 2021, were $61.2 million compared to $22.8 million for the comparable prior year period. The increase was primarily due to higher expenses related to commercial activities to support the ORGOVYX and MYFEMBREE U.S. launches, higher personnel-related costs primarily due to the hiring of Myovant’s commercial operations, marketing, and market access teams, as well as the oncology and women’s health sales forces, and higher general overhead expenses to support Myovant’s organizational growth.

Interest expense was $3.5 million for the three months ended June 30, 2021, compared to $2.2 million for the comparable prior year period. The increase in interest expense was primarily driven by the higher balance under Myovant’s loan agreement with Sumitomo Dainippon Pharma (Sumitomo Dainippon Pharma Loan Agreement) and $0.6 million of accretion of the financing component of the cost share advance from Pfizer.

Foreign exchange gain for the three months ended June 30, 2020 was $3.6 million, primarily the result of the increase in Myovant’s outstanding balance under the Sumitomo Dainippon Pharma Loan Agreement and the impact of fluctuations in the foreign currency exchange rate between the Swiss franc and the U.S. dollar. As a result of a change in the functional currency of Myovant’s wholly-owned subsidiary in Switzerland, Myovant Sciences GmbH, from the Swiss franc to the U.S. dollar in December 2020, Myovant is no longer exposed to significant foreign currency gains or losses.

Net loss for the three months ended June 30, 2021 was $61.7 million compared to $32.9 million for the comparable prior year period. On a per common share basis, net loss was $0.67 and $0.37 for the three months ended June 30, 2021 and 2020, respectively.

Capital resources: Cash, cash equivalents, marketable securities, and amounts available under the Sumitomo Dainippon Pharma Loan Agreement totaled $611.1 million as of June 30, 2021, and consisted of $569.8 million of cash, cash equivalents, and marketable securities and $41.3 million of available borrowing capacity under the Sumitomo Dainippon Pharma Loan Agreement. Subsequent to the end of the quarter, Myovant received a $100.0 million milestone payment from Pfizer in July 2021 and expects to receive a $15.0 million milestone payment from Richter in second fiscal quarter 2021.

Conference Call
As previously announced, Myovant will hold a webcast and conference call at 8:30 a.m. Eastern Time (5:30 a.m. Pacific Time) today, July 28, 2021, to discuss financial results for its first fiscal quarter ended June 30, 2021 and corporate updates. Investors and the general public may access a live webcast of the call by visiting the investor relations page of Myovant’s website at investors.myovant.com. Institutional investors and analysts may also participate in the conference call by dialing 1-800-532-3746 in the U.S. or +1-470-495-9166 from outside the U.S. The webcast will be archived on Myovant’s Investor Relations website following the call.

About Relugolix
Relugolix is a once-daily, oral gonadotropin-releasing hormone (GnRH) receptor antagonist that reduces testicular testosterone, a hormone known to stimulate the growth of prostate cancer, and ovarian estradiol, a hormone known to stimulate the growth of uterine fibroids and endometriosis. ORGOVYX (relugolix 120 mg) was approved in the U.S. by the FDA in December 2020 as the first and only oral GnRH receptor antagonist for the treatment of adult patients with advanced prostate cancer, and relugolix (120 mg) is also under regulatory review in Europe for men with advanced prostate cancer. MYFEMBREE (relugolix 40 mg, estradiol 1.0 mg, and norethindrone acetate 0.5 mg) was approved in the U.S. by the FDA in May 2021 as the first and only once-daily oral treatment for the management of heavy menstrual bleeding associated with uterine fibroids. On July 16, 2021, the European Commission approved RYEQO (relugolix 40 mg, estradiol 1.0 mg, and norethindrone acetate 0.5 mg) as the first and only long-term, once-daily oral treatment in Europe for moderate to severe symptoms of uterine fibroids in adult women of reproductive age. On July 6, 2021, Myovant Sciences GmbH, a subsidiary of Myovant Sciences Ltd., submitted a supplemental New Drug Application to the FDA for once-daily MYFEMBREE for the management of moderate to severe pain associated with endometriosis. MYFEMBREE is also being assessed for contraceptive efficacy in women ages 18-35 years who are at risk for pregnancy, pending FDA removal of a partial clinical hold.

On July 28, 2021 Mersana Therapeutics, Inc. (NASDAQ:MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, reported the initiation of patient dosing in UPGRADE, a Phase 1 combination dose escalation umbrella study to evaluate the safety and efficacy of upifitamab rilsodotin (UpRi, previously XMT-1536) in combination with other ovarian cancer therapies (Press release, Mersana Therapeutics, JUL 28, 2021, View Source [SID1234585258]). The initial arm of this umbrella study is evaluating carboplatin in combination with UpRi followed by continuation of UpRi monotherapy in patients with platinum-sensitive ovarian cancer.

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"The initiation of UPGRADE is another important milestone for Mersana as we work to build UpRi into a foundational medicine in the treatment of ovarian cancer," said Anna Protopapas, President and Chief Executive Officer of Mersana Therapeutics. "To date, UpRi data has demonstrated clinically meaningful activity and a differentiated tolerability profile without severe neutropenia, peripheral neuropathy or ocular toxicity in patients with heavily pretreated platinum-resistant ovarian cancer. The initiation of the UPGRADE umbrella study is a critical first step in evaluating the potential of UpRi in earlier lines of therapy."

The UPGRADE Phase 1, open-label, dose-escalation portion of the study will determine the maximum tolerated dose (MTD) and safety and tolerability of a once-every-four-week (Q4W) administration of UpRi in combination with carboplatin for six cycles followed by continuation of UpRi monotherapy in patients with platinum-sensitive high-grade serous ovarian cancer following 1-2 prior platinum-based regimens. Patients will not be preselected for NaPi2b expression; however, archival or fresh tissue will be required for retrospective assessment of expression. Upon completion of the dose-escalation portion of the study, the Company plans to initiate the expansion portion to assess both tolerability and efficacy and inform the further development of UpRi in a broader and earlier-line patient population.

"We are excited to initiate UPGRADE and are beginning with a platinum combination because platinum remains the mainstay therapy in earlier-line platinum-sensitive ovarian cancer. UPGRADE is intended to allow us to assess the advantages of combining with carboplatin for six cycles and replacing paclitaxel, an agent that carries significant toxicities. We will also evaluate the benefit of continuing treatment with UpRi as a single agent beyond the six cycles of combination therapy," said Arvin Yang, M.D., Ph.D., Senior Vice President and Chief Medical Officer of Mersana Therapeutics. "In the future, we plan to evaluate non-platinum-based combinations in this umbrella study to assess the potential of bringing UpRi to patients who do not benefit from platinum. We believe UpRi’s differentiated tolerability profile without the overlapping toxicities commonly seen with other ADC platforms may provide a significant advantage as a combination therapy for people living with ovarian cancer."

On July 28, 2021 Karyopharm Therapeutics Inc. (NASDAQ: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported dosing of the first patients in two new company-sponsored Phase 2 and 1/2 clinical studies evaluating XPOVIO (selinexor), the Company’s first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound in combination with approved therapies in patients with advanced melanoma and in patients with treatment naïve myelofibrosis (Press release, Karyopharm, JUL 28, 2021, View Source [SID1234585257]). These company-sponsored studies follow encouraging results from preclinical research and earlier stage, investigator-sponsored clinical studies conducted by Karyopharm’s scientific collaborators.

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"Despite recent advances in treatment options for both metastatic melanoma and myelofibrosis, far too many patients either do not respond or have short-lived responses to currently available treatment options, making the development of novel drug treatment approaches incredibly important for these diseases," said Sharon Shacham, PhD, MBA, Chief Scientific Officer of Karyopharm. "Substantial need remains for continued research into new druggable targets and identifying multiple targets and pathways that have the potential to be inhibited synergistically using combination approaches. We believe XPOVIO’s oral administration, along with its novel mechanism of action, make it a promising treatment candidate for new, single and synergistic combination regimens across both hematologic and solid tumors."

Summary of Newly Initiated Clinical Studies:

A Phase 2 Study Evaluating XPOVIO in Combination with Keytruda (pembrolizumab) in Recurrent Advanced Melanoma

This Phase 2, multicenter, open-label study (XPORT-MEL-033; NCT04768881) will evaluate the safety and efficacy of XPOVIO in combination with Keytruda and is expected to enroll approximately 40 patients with locally advanced or metastatic melanoma that is resistant to initial checkpoint inhibitor therapy. Patients will receive once-weekly oral XPOVIO (80mg) and Keytruda (400mg intravenously once every six weeks) until disease progression, toxicity or withdrawal from the study, whichever occurs first. The primary endpoint of the study is overall response rate (ORR). Secondary endpoints include safety, progression-free survival, overall survival (OS), and complete response rate, among several others.

Preclinical studies have shown that XPOVIO selectively kills malignant melanoma cells and synergistically increases the antitumor activity of check point inhibitors1,2,3. Two early clinical studies, one investigating XPOVIO as a single agent4 and one investigating XPOVIO plus Keytruda5, in heavily pretreated advanced melanoma, have shown that this activity is borne out in clinical studies.

A Phase 1/2 Study Evaluating XPOVIO in Combination with Jakafi (ruxolitinib) in Treatment Naïve Myelofibrosis

This global Phase 1/2, multicenter, open-label study (XPORT-MF-034; NCT04562389) will evaluate the safety and efficacy of XPOVIO in combination with Jakafi and is expected to enroll approximately 237 patients with treatment naïve myelofibrosis. The study will be conducted in two phases: Phase 1a/1b and Phase 2. The Phase 1a dose escalation portion of the study will determine the maximum tolerated dose and the recommended Phase 2 dose (RP2D) and will evaluate safety and preliminary efficacy. The Phase 1b dose expansion portion of the study will be conducted at the determined RP2D and will further assess the safety and preliminary efficacy at this dose level. In the Phase 2 portion of the study, patients will be randomized 1:1 to receive either once weekly XPOVIO plus Jakafi (15mg or 20mg twice daily) or Jakafi (15mg or 20mg twice daily) monotherapy. The primary endpoint for the Phase 2 portion of the study is the percentage of patients who achieve spleen volume reduction of at least 35% from baseline. Secondary endpoints for the Phase 2 portion of the study include safety, percentage of patients who achieve total symptom score reduction of ≥50%, OS, anemia response and ORR, among several others.

This new Phase 1/2 study is supported by multiple preclinical data sets which showed that (i) nuclear cytoplasmic transport is essential for survival of JAK2V617F-mutant HEL cells in vitro, a major vulnerability and a potential therapeutic target in MF6, (ii) that XPOVIO significantly reduced white blood cells (WBCs), granulocytes and spleen GFP+ cells in in vivo models of JAK2V617F-driven myeloproliferative neoplasms, and (iii) the combination of XPOVIO and ruxolitinib in vivo showed significant reduction in WBCs, granulocytes, spleen GFP+ cells, as well as in spleen weight when compared to either agent alone7. Collectively, these data support the clinical investigation of XPOVIO combined with ruxolitinib in patients with myelofibrosis.

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 two 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.

For additional product information, including full prescribing information, please visit www.XPOVIO.com.

On July 28, 2021 Integra LifeSciences Holdings Corporation (NASDAQ: IART), a leading global medical technology company, reported financial results for the second quarter ending June 30, 2021 (Press release, Integra LifeSciences, JUL 28, 2021, View Source [SID1234585256]).

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"We are pleased with second quarter results that exceeded our forecasts. Our business segments were well-positioned to capitalize on the improving demand driven by the ongoing global market recovery," said Peter Arduini, Integra’s president and chief executive officer. "We saw particularly healthy order activity in products used in neurosurgery, instruments, burn, trauma and surgical reconstruction as markets gradually recovered. Areas such as capital equipment and our international indirect markets are still early in their recovery but are reporting encouraging trends. As a result of our better than expected second quarter financial performance, we are raising our full-year revenue and EPS guidance."

Second Quarter 2021 Consolidated Performance

Total reported revenues of $390.0 million increased 50.8% on a reported basis and 48.7% on an organic basis compared to the prior year. Total reported revenues include $17.7 million from the acquisition of ACell, which was completed on January 20, 2021.

The Company reported GAAP gross margin of 61.2%, compared to 59.2% in the second quarter of 2020. Adjusted gross margin was 68.1% compared to 66.2% in the prior year.

Adjusted EBITDA for the second quarter of 2021 was $101.0 million, or 25.9% of revenue, compared to $52.8 million, or 20.4% of revenue in the prior year. Adjusted EBITDA margins benefited from higher revenue and higher adjusted gross margins, partially offset by higher operating expenses attributable to the gradual return of spending, which was reduced during the same period in the prior year in response to the global pandemic.

The Company reported GAAP net income of $35.1 million, or $0.41 per diluted share, in the second quarter of 2021, compared to a GAAP net loss of $(0.4 million), or $(0.00) per diluted share, in the prior year.

Adjusted net income for the second quarter of 2021 was $67.4 million, or $0.79 per diluted share, compared to $28.4 million, or $0.33 per diluted share, in the prior year.

Second Quarter 2021 Segment Performance

Codman Specialty Surgical (66% of Revenues)

Total revenues were $256.8 million, representing reported growth of 51.3% and organic growth of 49.5% compared to the second quarter of 2020. Broad-based strength in both neurosurgery and instruments were driven by a recovery in demand.
Tissue Technologies (34% of Revenue)

Total revenues were $133.2 million, representing reported growth of 49.8% and organic growth of 47.1% compared to the second quarter of 2020. Growth was led by strength in burn, trauma and surgical reconstruction.
Strategic Initiatives and Key Developments

Advancing key products

Cerelink – next generation intracranial pressure monitor is scheduled for a controlled market release in the third quarter.
Aurora Surgiscope in minimally invasive tumor removal procedures – a targeted phased market launch will begin in the third quarter to generate clinical evidence and gain insights for a broader commercial launch in the second half of 2022.
PriMatrix Dermal Repair Scaffold – during the second quarter, the Company completed a randomized clinical study of PriMatrix for use in the closure of Diabetic Foot Ulcers (DFUs). This multi-center study enrolled over 225 patients and found that PriMatrix demonstrated statistically and clinically significant results, healing more DFUs in 12 weeks versus standard of care, with a median number of one application. The results of this study have been published in the Journal of Wound Care.
The Company announced that Peter Arduini will step down as Chief Executive Officer at the end of 2021 to accept the role of President and Chief Executive Officer of GE Healthcare. The Board of Directors has initiated a formal search and appointed a special committee to direct the search and ensure a seamless transition of responsibilities.
Balance Sheet, Cash Flow and Capital Allocation

The Company generated cash flow from operations of $91.3 million in the quarter. The Company paid down $100 million of debt on its senior credit facility during the second quarter. Net debt at the end of the quarter was $1,166 million and the consolidated total leverage ratio was 2.4x, an improvement of 0.6x from December 31, 2020.

As of quarter end, the Company had total liquidity of approximately $1.7 billion, including approximately $397 million in cash and the remainder available under the revolving credit facility.

2021 Outlook

The Company is providing forward-looking guidance regarding adjusted earnings per diluted share, but is not providing a reconciliation to GAAP earnings per share, because certain GAAP expense items are highly variable and management is unable to predict them with reasonable certainty and without unreasonable effort. Specifically, the financial impact and timing of divestitures, acquisitions, integrations, structural optimization and efforts to comply with the EU Medical Device Regulation are uncertain, depend on various dynamic factors and are not reasonably ascertainable at this time. These expense items could have a material impact on GAAP results. Adjusted earnings per diluted share also excludes the impact of intangible asset amortization associated with prior business acquisitions, which we expect to be approximately $0.71 per diluted share for the full-year 2021.

In addition, the Company will continue to monitor the ongoing uncertainty around the scope and duration of the pandemic and its impact on financial performance. The Company does not expect the ongoing impact of the pandemic to be uniform across all markets and product lines. The Company’s guidance assumes a gradual improvement in surgical procedures with no further setbacks from new surges or new COVID variants.

Full-Year 2021 Outlook

The Company is raising its full-year 2021 revenue guidance by $15 million to a range of $1,540 million to $1,550 million from $1,525 million to $1,535 million. This new guidance range represents a reported growth range of 12% to 13% and an organic growth range of 13% to 14%. The Company is also raising its full-year 2021 adjusted earnings per share guidance to new range of $2.98 to $3.05, from its prior range of $2.86 to $2.93.

The Company has revised its outlook for a revenue contribution from ACell to $70 million to $74 million for the full-year 2021, from its previous range of $83 million to $88 million, due to the impact of an accelerated integration of the sales force during the pandemic. The Company remains confident in the long-term growth expectations for the ACell portfolio. Strong performance in other parts of the CSS and TT businesses more than offset the slower start in ACell and are included in the new total company revenue guidance range.

Third Quarter Outlook

For the third quarter 2021, the Company expects revenues to be in a range of $382 million to $389 million, representing reported growth of approximately 3% to 5% and organic growth of 5% to 7%. Adjusted earnings per diluted share are expected to be in a range of $0.71 to $0.74.

In the future, the Company may record, or expects to record, gains or losses, expenses, or charges as described in the Discussion of Adjusted Financial Measures below, which will be excluded from the calculation of adjusted EBITDA, adjusted earnings per share for historical periods and in adjusted earnings per share guidance.

Conference Call and Presentation Available Online

Integra has scheduled a conference call for 8:30 a.m. ET today, Wednesday, July 28, 2021, to discuss financial results for the second quarter. The conference call will be hosted by Integra’s senior management team and will be open to all listeners. Additional forward-looking information may be discussed in a question and answer session following the prepared remarks.

Integra’s management team will reference a presentation during the conference call. The presentation can be found on investor.integralife.com.

Access to the live call is available by dialing (800) 367-2403 and using the passcode 3706513. The call can also be accessed via a webcast link provided on investor.integralife.com. A replay of the call will be available until August 7, 2021 by dialing (888) 203-1112 and using the passcode 3706513. The webcast will also be archived on the website.

On July 28, 2021 Clarity Pharmaceuticals, a clinical stage radiopharmaceutical company focused on the treatment of serious disease, reported that it has commenced its 64/67Cu SAR-bisPSMA theranostic clinical trial in patients with metastatic castrate resistant prostate cancer (mCRPC) in the US (Press release, Clarity Pharmaceuticals, JUL 28, 2021, View Source [SID1234585255]). Patient recruitment has commenced with the opening of the first clinical site at the Urology Cancer Center and GU Research Network in Omaha, Nebraska.

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Clarity’s Executive Chairman, Dr Alan Taylor, commented, "The prostate cancer market is a key focus for Clarity and we are very pleased to commence this clinical trial for men with mCRPC using our optimised theranostic PSMA products, 64/67Cu SAR-bisPSMA. The exciting news about the commencement of the SECuRE trial (NCT04868604)1 comes shortly after the initiation of our diagnostic 64Cu SAR-bisPSMA clinical trial called PROPELLER (NCT04839367)2. Clarity’s SAR-bisPSMA products hold great promise of improving prostate cancer diagnosis and treatment and have the potential to provide multiple benefits in comparison to current products in the market."

The SECuRE trial is a Phase I/IIa theranostic trial for identification and treatment of PSMA-expressing mCRPC using Targeted Copper Theranostics (TCT). 64Cu SAR-bisPSMA is used for diagnosis and selection of patients and 67Cu SAR-bisPSMA for therapy. It is a multi-centre, single arm, dose escalation study with a cohort expansion planned for up to 44 patients in the US. The aim of this study is to determine the safety and efficacy of 67Cu-SAR-bisPSMA as a therapy.

Dr Taylor said: "We look forward to progressing both the SECuRE and PROPELLER trials in patients with prostate cancer to build on the compelling results from our therapeutic and diagnostic preclinical studies. There is a high unmet need for early detection and better treatment options for patients with prostate cancer, especially with mCRPC, for which the median life expectancy is less than three years. We believe that the TCT hold great promise for this patient population due to the logistical, manufacturing and treatment benefits associated with the optimised SAR-bisPSMA product and the "perfect pairing" of copper-64 (64Cu) and copper-67 (67Cu) radioisotopes. We look forward to progressing these trials and getting closer to achieving our ultimate goal of developing better treatments for children and adults with cancer."