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."

On June 28, 2021 Bristol Myers Squibb (NYSE:BMY) reported that results for the second quarter of 2021, which reflect robust product sales, continued advancement of the pipeline and strong clinical and operational performance across the company (Press release, Bristol-Myers Squibb, JUL 28, 2021, View Source [SID1234585254]).

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"We delivered a strong quarter across each of our four therapeutic areas, including building momentum for our new product portfolio and Opdivo returning to growth," said Giovanni Caforio, M.D., board chair and chief executive officer, Bristol Myers Squibb. "We achieved significant clinical and regulatory milestones reflecting the hard work and dedication of our team, who together have built a portfolio of best-in-class medicines to meet the needs of patients with serious diseases. As we move forward, we remain focused on driving inline product performance, progressing our new launches, and advancing pipeline opportunities. Our robust and diverse pipeline combined with our clinical and commercial execution strengthen our confidence in our ability to renew the portfolio and achieve sustained growth."

All comparisons are made versus the same period in 2020 unless otherwise stated.

Bristol Myers Squibb posted second quarter revenues of $11.7 billion, an increase of 16%, or 13% when adjusted for foreign exchange. Sales in the same period a year ago were negatively impacted by approximately $350 million of COVID-19-related channel inventory work downs.
U.S. revenues increased 14% to $7.4 billion in the quarter. International revenues increased 18% to $4.3 billion in the quarter. When adjusted for foreign exchange impact, international revenues increased 10%.
Gross margin increased from 73.4% to 79.0% in the quarter primarily due to lower unwinding of inventory purchase price accounting adjustments, partially offset by foreign exchange.
On a non-GAAP basis, gross margin decreased from 80.5% to 79.8% in the quarter driven by foreign exchange and product mix.
Marketing, selling and administrative expenses increased 16% to $1.9 billion in the quarter on a GAAP and non-GAAP basis primarily due to higher advertising and promotion expenses, higher costs to support new product launches and lower spending in the prior year due to COVID-19.
Research and development expenses increased 30% to $3.3 billion in the quarter primarily due to higher license and asset acquisition charges and an in-process research and development (IPR&D) impairment charge.
On a non-GAAP basis, research and development expenses increased 4% to $2.3 billion in the quarter primarily due to higher costs associated with the broader portfolio and lower spending in the prior year due to COVID-19.
Amortization of acquired intangible assets increased $158 million to $2.5 billion in the quarter.
The effective tax rate was 31.7% in the quarter. Income taxes were $1.7 billion on pre-tax earnings of $1.6 billion in the same period a year ago primarily due to tax charges resulting from an internal transfer of certain intangible assets and the Otezla divestiture and purchase price adjustments.
On a non-GAAP basis, the effective tax rate increased 3.1% to 16.9% in the quarter primarily driven by earnings mix.
The company reported net earnings attributable to Bristol Myers Squibb of $1.1 billion, or $0.47 per share, in the second quarter, compared to net loss of $85 million, or $0.04 per share, for the same period a year ago.
The company reported non-GAAP net earnings attributable to Bristol Myers Squibb of $4.3 billion, or $1.93 per share, in the second quarter, compared to non-GAAP net earnings of $3.8 billion, or $1.63 per share, for the same period a year ago.
A discussion of the non-GAAP financial measures is included under the "Use of Non-GAAP Financial Information" section.

*In excess of +100%.

**Included as part of the new product portfolio

SECOND QUARTER PRODUCT AND PIPELINE UPDATE

Cardiovascular

mavacamten

Medical Meeting

In May, at the American College of Cardiology’s 70th Annual Scientific Session (ACC.21), the company presented:
New analysis of data from the Phase 3 EXPLORER-HCM study that demonstrated a Health Status Benefit in patients with obstructive hypertrophic cardiomyopathy (oHCM) receiving mavacamten compared to placebo. The data were simultaneously published in The Lancet.(link)
Interim results from MAVA-LTE, an ongoing, dose-blinded five-year extension study of the EXPLORER-HCM Phase 3 trial, which demonstrated that in patients with oHCM, mavacamten was well tolerated and showed durable improvement in left ventricular outflow tract gradients, diastolic function, N-terminal-pro hormone B-type natriuretic peptide and symptoms. (link)
Results from a real-world data analysis measuring the clinical and economic burden of oHCM in the United States, which found the condition is associated with substantial healthcare resource utilization and costs. (link)
Oncology

Opdivo

Regulatory

In June, the company announced that the European Commission (EC) has approved Opdivo(nivolumab) plus Yervoy (ipilimumab) for the treatment of adult patients with mismatch repair deficient or microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer (mCRC) after prior fluoropyrimidine-based combination chemotherapy. The EC approval is based on results from the Phase 2 CheckMate -142 study (link). In May, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended approval for this indication (link)
In June, the company announced that the CHMP of the EMA has recommended approval of Opdivo for the adjuvant treatment of adult patients with esophageal or gastroesophageal junction cancer (GEJC) who have residual pathologic disease following prior neoadjuvant chemoradiotherapy (CRT). The recommendation is based on results from the Phase 3 CheckMate -577 study in which Opdivo doubled disease-free survival compared to placebo in the all-randomized population. (link)
In June, the company announced that the EC has approved Opdivo plus Yervoy for the first-line treatment of adults with unresectable malignant pleural mesothelioma (MPM). The EC’s decision is based on results from the CheckMate -743 study, the first and only positive Phase 3 study of an immunotherapy in first-line MPM.(link)
In May, the company announced that the U.S. Food & Drug Administration (FDA) has approved Opdivo for the adjuvant treatment of completely resected esophageal cancer or GEJC with residual pathologic disease in patients who have received neoadjuvant CRT. The FDA approval is based on results from the Phase 3 CheckMate -577 study. (link)
In April, the company announced that the FDA has accepted the supplemental Biologics License Application for Opdivo for the adjuvant treatment of patients with surgically resected, high-risk muscle-invasive urothelial carcinoma, based on results from the Phase 3 CheckMate -274 study. The FDA granted the application Priority Review and assigned a Prescription Drug User Fee Act goal date of September 3, 2021. (link)
Clinical

Today, the company announced that the Phase 3 CheckMate -649 trial did not meet the secondary endpoint of overall survival (OS) with the combination of Opdivoplus Yervoyas compared to chemotherapy as a first-line treatment for metastatic gastric cancer (GC), GEJC or esophageal adenocarcinoma (EAC) in patients whose tumors express PD-L1 with a combined positive score (CPS) ≥ 5, at a final analysis. The safety profiles of Opdivoand Yervoyin this trial were consistent with those previously reported for other tumor types. These data have no impact on the U.S. indication for Opdivo plus chemotherapy for the treatment of patients with advanced or metastatic GC, GEJC and EAC, regardless of PD-L1 expression status, which received full approval from the FDA based on results from the CheckMate -649 study.
In July, the company announced an update on the Phase 3 CheckMate -651 study comparing Opdivo plus Yervoy to the EXTREME regimen (cetuximab, cisplatin/carboplatin and fluorouracil) as a first-line treatment in platinum-eligible patients with recurrent or metastatic squamous cell carcinoma of the head and neck. Although Opdivoplus Yervoyshowed a clear, positive trend towards OS in patients whose tumors express PD-L1 with a combined CPS ≥ 20, the study did not meet its primary endpoints. (link)
Medical Meetings

In May and June, the company announced new data and analyses across its cancer portfolio (link) that were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 Annual Meeting, including results from the:
Phase 2/3 RELATIVITY-047 study, which showed that the fixed-dose combination of relatlimab, a LAG-3-blocking antibody, and nivolumab, administered as a single infusion, demonstrated a statistically significant and clinically meaningful progression-free survival benefit compared to Opdivo alone in patients with previously untreated metastatic or unresectable melanoma. (link)
Phase 3 CheckMate -648 study, in which two Opdivo-based treatment combinations — Opdivoplus chemotherapy and Opdivoplus Yervoy— demonstrated a statistically significant and clinically meaningful OS benefit compared to chemotherapy at the pre-specified interim analysis in patients with unresectable advanced or metastatic esophageal squamous cell carcinoma with tumor cell PD-L1 expression ≥1%, as well as in the all-randomized population. (link)
Six-and-a-half-year follow-up analysis from the Phase 3 CheckMate -067 study, which showed a continued, durable improvement in OS with Opdivo plus Yervoytherapy and Opdivomonotherapy, versus Yervoy alone, in patients with previously untreated advanced melanoma. (link)
Two-year follow-up analysis from the Phase 3 CheckMate -9LA study, which demonstrated that OpdivoplusYervoywith two cycles of chemotherapy showed a durable survival benefit compared to four cycles of chemotherapy alone after two years in patients with previously untreated, advanced non-small cell lung cancer (NSCLC). (link)
Four-year follow-up analysis from Part 1 of the Phase 3 CheckMate -227 study, which demonstrated a durable, long-term survival benefit of first-line treatment with Opdivoplus Yervoycompared to chemotherapy in patients with previously untreated, advanced NSCLC with a minimum follow-up of over four years (49.4 months). (link)
Hematology

Abecma

Regulatory

In June, the company announced the CHMP of the EMA has recommended granting Conditional Marketing Authorization for Abecma (idecabtagene vicleucel; ide-cel), the company’s B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell immunotherapy, for the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody and have demonstrated disease progression on the last therapy. The CHMP opinion was based on results from the pivotal Phase 2 KarMMa study. (link)
Breyanzi

Clinical

In June, the company announced positive topline results from TRANSFORM, a global, randomized, multicenter Phase 3 study evaluating Breyanzi(lisocabtagene maraleucel) as a second-line treatment in adults with relapsed or refractory large B-cell lymphoma (LBCL) compared to salvage therapy followed by high-dose chemotherapy and hematopoietic stem cell transplant, which is currently considered a gold standard treatment for these patients. (link)
Onureg

Regulatory

In June, the company announced that the EC has granted full Marketing Authorization for Onureg (azacitidine tablets) as a maintenance therapy in adult patients with acute myeloid leukemia who achieved complete remission or complete remission with incomplete blood count recovery (CRi) following induction therapy with or without consolidation treatment and who are not candidates for, including those who choose not to proceed to, hematopoietic stem cell transplantation. The EC approval was based on results from the QUAZAR AML-001 study. (link)
Medical Meetings

In June, at the 26th European Hematology Association (EHA) (Free EHA Whitepaper), the company announced new data and analyses from the:
Phase 2 BEYOND study with Acceleron Pharma Inc. (NASDAQ: XLRN), which showed treatment with Reblozyl (luspatercept-aamt), a first-in-class erythroid maturation agent, plus best supportive care compared to placebo improved anemia in adult patients with non-transfusion dependent beta thalassemia. (link)
In May, at the ASCO (Free ASCO Whitepaper) 2021 Annual Meeting, the company announced new data and analyses from the:
Pivotal Phase 2 KarMMa study with bluebird bio, Inc. (NASDAQ: BLUE), which showed patients treated with Abecmaachieved an overall response rate that remained consistent or achieved a complete response or better after a median follow-up of 24.8 months. The data represent the longest follow-up to date from a global clinical trial of a CAR T cell therapy in multiple myeloma. (link)
Immunology

Zeposia

Regulatory

In May, the company announced that the FDA approved Zeposia (ozanimod) for the treatment of adults with moderately to severely active ulcerative colitis, a chronic inflammatory bowel disease. The approval is based on data from the pivotal, Phase 3 True North study. (link)
Business Development

In June, the company and Eisai Co., Ltd. announced that the companies have entered into an exclusive global strategic collaboration agreement for the co-development and co-commercialization of MORAb-202, an antibody drug conjugate. (link)
In May, the company and Agenus Inc. (NASDAQ: AGEN) announced that they have entered into a definitive agreement under which Bristol Myers Squibb will be granted a global exclusive license to Agenus’ proprietary bispecific antibody program, AGEN1777, that blocks TIGIT and a second undisclosed target. (link)
Financial Guidance

Bristol Myers Squibb is updating its 2021 GAAP EPS guidance range of $3.18 – $3.38 to $2.77 – $2.97 and reaffirming its non-GAAP EPS guidance range of $7.35 – $7.55. Both GAAP and non-GAAP guidance assume current exchange rates. Key 2021 GAAP and non-GAAP line-item guidance assumptions are:

Worldwide revenues increasing in the high-single digits.
Gross margin as a percentage of revenue is expected to be approximately 79% for GAAP and approximately 80% for non-GAAP.
Marketing, selling and administrative expenses to be in-line with 2020 levels for GAAP and increasing in the low-single digits for non-GAAP.
Research and development expenses decreasing in the low-single digits for GAAP and increasing in the mid-single digits for non-GAAP.
An effective tax rate of approximately 23% for GAAP and approximately 16% for non-GAAP.
The 2021 financial guidance excludes the impact of any potential future strategic acquisitions and divestitures, and any specified items that have not yet been identified and quantified. The 2021 non-GAAP EPS guidance is explained and further excludes other specified items as discussed under "Use of Non-GAAP Financial Information." The financial guidance is subject to risks and uncertainties applicable to all forward-looking statements as described elsewhere in this press release.

Company and Conference Call Information

Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook, and Instagram.

There will be a conference call on July 28, 2021 at 8 a.m. ET during which company executives will review financial information and address inquiries from investors and analysts. Investors and the general public are invited to listen to a live webcast of the call at View Source or by using this link which becomes active 15 minutes prior to the scheduled start time and entering your information to be connected. Investors and the general public can also access the live webcast by dialing in the U.S. toll free 888-204-4368 or international +1 313-209-4906, confirmation code: 1720109. Materials related to the call will be available at the same website prior to the conference call.

A replay of the call will be available beginning at 11:30 a.m. ET on July 28 through 11:30 a.m. ET on August 11, 2021. The replay will also be available through View Source or by dialing in the U.S. toll free 888-203-1112 or international +1 719-457-0820, confirmation code: 1720109.

Use of Non-GAAP Financial Information

In discussing financial results and guidance, the company refers to financial measures that are not in accordance with U.S. Generally Accepted Accounting Principles (GAAP). The non-GAAP financial measures are provided as supplemental information to the financial measures presented in this press release that are calculated and presented in accordance with GAAP and are presented because management has evaluated the company’s financial results both including and excluding the adjusted items or the effects of foreign currency translation, as applicable, and believes that the non-GAAP financial measures presented portray the results of the company’s baseline performance, supplement or enhance management, analysts and investors overall understanding of the company’s underlying financial performance and trends and facilitate comparisons among current, past and future periods. For example, non-GAAP earnings and EPS information are indications of the company’s baseline performance before items that are considered by us to not be reflective of the company’s ongoing results. This information is among the primary indicators that we use as a basis for evaluating performance, allocating resources, setting incentive compensation targets and planning and forecasting for future periods. In addition, non-GAAP gross margin, which is gross profit excluding certain specified items as a percentage of revenues, non-GAAP marketing, selling and administrative expenses, which is marketing, selling and administrative expense excluding certain specified items, and non-GAAP research and development expenses, which is research and development expenses excluding certain specified items, are relevant and useful for investors because they allow investors to view performance in a manner similar to the method used by our management and make it easier for investors, analysts and peers to compare our operating performance to other companies in our industry and to compare our year-over-year results.

This earnings release and the accompanying tables also provide certain revenues and expenses as well as non-GAAP measures excluding the impact of foreign exchange. We calculate foreign exchange impacts by converting our current-period local currency financial results using the prior period average currency rates and comparing these adjusted amounts to our current-period results.

Non-GAAP financial measures such as non-GAAP earnings and related EPS information are adjusted to exclude certain costs, expenses, gains and losses and other specified items that are evaluated on an individual basis after considering their quantitative and qualitative aspects and typically have one or more of the following characteristics, such as being highly variable, difficult to project, unusual in nature, significant to the results of a particular period or not indicative of past or future operating results. These items are excluded from non-GAAP earnings and related EPS information because the company believes they neither relate to the ordinary course of the company’s business nor reflect the company’s underlying business performance. Similar charges or gains were recognized in prior periods and will likely reoccur in future periods, including amortization of acquired intangible assets, including product rights that generate a significant portion of our ongoing revenue and will recur until the intangible assets are fully amortized, unwind of inventory fair value adjustments, acquisition and integration expenses, restructuring costs, accelerated depreciation and impairment of property, plant and equipment and intangible assets, R&D charges or other income resulting from upfront or contingent milestone payments in connection with the acquisition or licensing of third-party intellectual property rights, divestiture gains or losses, stock compensation resulting from accelerated vesting of Celgene awards, certain retention-related employee compensation charges related to the Celgene transaction, pension, legal and other contractual settlement charges, equity investment and contingent value rights fair value adjustments (including fair value adjustments attributed to limited partnership equity method investments beginning in 2021) and amortization of fair value adjustments of debt acquired from Celgene in our 2019 exchange offer, among other items. Certain other significant tax items are also excluded such as the impact resulting from internal transfer of intangible assets and the Otezla* divestiture in the second quarter 2020. Deferred and current income taxes attributed to these items are also adjusted for considering their individual impact to the overall tax expense, deductibility and jurisdictional tax rates.

Because the non-GAAP financial measures are not calculated in accordance with GAAP, they should not be considered superior to and are not intended to be considered in isolation or as a substitute for the related financial measures presented in the press release that are prepared in accordance with GAAP and may not be the same as or comparable to similarly titled measures presented by other companies due to possible differences in method and in the items being adjusted. We encourage investors to review our financial statements and publicly-filed reports in their entirety and not to rely on any single financial measure.

Reconciliations of the non-GAAP financial measures to the most comparable GAAP measures are provided in the accompanying financial tables and also available on the company’s website at www.bms.com. Within the attached financial tables presented, certain columns and rows may not add due to the use of rounded numbers. Percentages and earnings per share amounts presented are calculated from the underlying amounts.

Website Information

We routinely post important information for investors on our website, BMS.com, in the "Investors" section. We may use this website as a means of disclosing material, non-public information and for complying with our disclosure obligations under Regulation FD. Accordingly, investors should monitor the Investors section of our website, in addition to following our press releases, SEC filings, public conference calls, presentations and webcasts. We may also use social media channels to communicate with our investors and the public about our company, our products and other matters, and those communications could be deemed to be material information. The information contained on, or that may be accessed through, our website or social media channels are not incorporated by reference into, and are not a part of, this document.

On July 27, 2021 iOnctura SA, a clinical stage oncology company targeting core resistance and relapse mechanisms at the tumor-stroma-immune interface, announces the support of Innosuisse in a 2-year innovation project to explore the potential of iOnctura’s lead molecule, the PI3Kδ-inhibitor IOA-244, in the treatment of lymphoma (Press release, iOnctura, JUL 27, 2021, View Source [SID1234640245]).

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The Innosuisse grant of 596’828 CHF (approximately $652,000) will fund fifty percent of the project’s costs, covering the research carried out by Professor Francesco Bertoni of the Institute of Oncology Research (IOR) in Bellinzona, Switzerland.

The research project, scheduled to start in August 2021, will run alongside iOnctura’s expanding clinical program for IOA-244, focussed on the treatment of solid tumors (NCT04328844). Amongst other aspects, the new project will explore patient stratification biomarkers, combination interventions to increase treatment response rates in lymphoma and methods for minimizing potential resistance pathways.

"I am delighted iOnctura will be able to draw on the experience of Francesco Bertoni and his group to better understand the mechanisms of resistance in lymphoma. We want to understand precisely how to position IOA-244 in the treatment landscape of lymphoma in parallel to our clinical program in solid tumors." said Catherine Pickering, CEO of iOnctura. "In our ongoing solid tumor program with IOA-244 we are seeing clinical safety and activity behaviors consistently mirroring those we anticipated from our preclinical evaluations."

IOA-244 is highly selective for the PI3Kδ isoform and has a novel mechanism of target inhibition, binding the kinase without competing for ATP. This suite of properties contributes to IOA-244’s emerging unprecedented clinical profile. While first-generation PI3Kδ-inhibitors are being prescribed for the treatment of lymphoma, their use has been associated with compound-related toxicities, limiting their application as monotherapy and preventing their combination with standard therapies. Furthermore, resistance mechanisms associated with PI3kδ inhibitors remains an important field of research to address additional unmet medical need.

Professor Bertoni, the research partner at the IOR, commented, "Targeting PI3Kδ holds great promise for the treatment of patients with lymphoma. Unfortunately, previous drugs in this class have been hampered by safety issues and resistance. I am excited to be working on IOA-244, a novel PI3Kδ inhibitor, which not only has a unique binding mode, but based on initial clinical data also appears to be safe and combinable with other drugs – meaning we could translate our findings into meaningful treatment regimens for patients."

Project funding comes from Innosuisse, the Swiss national Innovation Agency which has a remit to promote science-based innovation to increase the competitiveness of small and medium-sized enterprises in Switzerland.

Project title: "Evaluation of non-ATP competitive PI3Kδ inhibition with IOA-244 in the treatment of lymphoma".