Novartis Kymriah® receives EC approval as first CAR-T cell therapy for adults with relapsed or refractory follicular lymphoma

On May 4, 2022 Novartis reported that the European Commission (EC) has approved Kymriah (tisagenlecleucel), a CAR-T cell therapy, for the treatment of adult patients with relapsed or refractory (r/r) follicular lymphoma (FL) after two or more lines of systemic therapy (Press release, Novartis, MAY 4, 2022, View Source [SID1234614190]). The approval follows a positive opinion in March by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) and is applicable to all 27 European Union member states plus Iceland, Norway and Liechtenstein. This approval marks the third indication for Kymriah and makes it the first CAR-T cell therapy approved in the EU for these patients, which include those with r/r FL grade 1, 2 and 3A1.

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"When follicular lymphoma fails to respond to treatment or comes back, it is typically more aggressive and difficult to treat; patients often end up cycling through multiple lines of therapy with decreasing benefit," said Catherine Thieblemont, MD, PhD, Professor of Hematology in the Paris VII- University, France and Head of the Hemato-Oncology Unit of St-Louis Hospital in Paris. "The approval of Kymriah in Europe brings patients closer to a potentially definitive therapy, providing us hope for improved outcomes."

The approval is based on the global Phase II ELARA trial showing that 86% of patients who were treated with Kymriah had a response, including 69% who had a complete response (CR)1. Prolonged durable response to treatment was demonstrated with an estimated 87% of patients who achieved a CR still in response at or more than nine months after initial response1. In the trial, 94 infused patients were evaluated for efficacy with a median follow-up of approximately 21 months1.

Among 97 patients evaluable for safety, the safety profile of Kymriah was remarkable1. Cytokine release syndrome (CRS) was reported in 50% of patients after Kymriah infusion, and no Grade 3 or 4 events were reported, as defined by the Lee scale1. Neurological adverse reactions occurred in 9% of patients (1% were Grade 3 or 4) within eight weeks after Kymriah infusion1. Severe infections (Grade 3 or 4) occurred in 16% of patients1.

"With this approval, we are pleased to be able to offer this transformative therapy to more people across the globe living with this advanced blood cancer," said Marie-France Tschudin, President, Innovative Medicines International & Chief Commercial Officer, Novartis. "With long-lasting responses and a safety profile that allows for flexible administration, we are striving to rewrite cancer survival and alleviate the burden of this disease for patients and the healthcare system."

In addition to r/r FL, Kymriah is approved for the treatment of pediatric and young adult patients up to and including 25 years of age with B cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse post-transplant or in second or later relapse, and adult patients with r/r diffuse large B cell lymphoma (DLBCL) after two or more lines of systemic therapy1.

About Novartis commitment to Oncology Cell Therapy
As part of the unique Novartis strategy to pursue four cancer treatment platforms – radioligand therapy, targeted therapy, immunotherapy and cell and gene therapy – we strive for cures through cell therapies in order to enable more patients to live cancer-free. We will continue to pioneer the science and invest in our manufacturing and supply chain process to further advance transformative innovation.

Novartis was the first pharmaceutical company to significantly invest in pioneering CAR-T research and initiate global CAR-T trials. Kymriah, the first approved CAR-T cell therapy, developed in collaboration with the Perelman School of Medicine at the University of Pennsylvania, is the foundation of the Novartis commitment to CAR-T cell therapy.

We have made strong progress in broadening our delivery of Kymriah, which is currently available for use in at least one indication in 30 countries and at more than 370 certified treatment centers, with clinical and real-world experience from administration to more than 6,900 patients. We continue to pioneer in cell therapy, leveraging our vast experience to develop next-generation CAR-T cell therapies. These therapies will utilize our new T-Charge platform being evaluated to expand across hematological malignancies and bring hope for a cure to patients with other cancer types.

Bristol Myers Squibb to Participate in Bank of America Securities 2022 Healthcare Conference

On May 4, 2022 Bristol Myers Squibb (NYSE: BMY) reported that the company will take part in a fireside chat at the Bank of America Securities 2022 Healthcare Conference in Las Vegas, Nevada on Wednesday, May 11, 2022 (Press release, Bristol-Myers Squibb, MAY 4, 2022, View Source [SID1234613470]). Adam Lenkowsky, Senior Vice President and General Manager, U.S. Commercialization, will answer questions about the company at 12:00 p.m. PT/3:00 p.m. ET.

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Investors and the general public are invited to listen to a live webcast of the session at View Source Material related to the company’s presentation will be available at the same website at the start of the live webcast. An archived edition of the session will be available later that day.

Fresenius with solid start to 2022 despite macroeconomic challenges

On May 4, 2022 Stephan Sturm, CEO of Fresenius reported that We have made a solid start into 2022 – somewhat better, even, than expected at Fresenius Helios and Fresenius Kabi (Press release, Fresenius, MAY 4, 2022, View Source [SID1234613502]). The first quarter was burdened by the ongoing coronavirus pandemic, the war in Ukraine, supply chain bottlenecks and, above all, cost increases that are in some cases significant. We will have to watch all these factors very closely. Still, our businesses developed well. With the announced transactions at Fresenius Kabi and Fresenius Medical Care we’ve taken important steps in the realization of our growth strategy, thereby improving the foundations for our future business success. We therefore continue to expect overall healthy sales and earnings growth, and to look ahead with confidence to the rest of our business year and beyond."

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FY/22 Group guidance confirmed
For FY/22, Fresenius confirms its guidance and projects sales growth1 in a mid-single-digit percentage range in constant currency. Net income2,3 is expected to grow in a low-single-digit percentage range in constant currency. Implicitly, net income2 for the Group excluding Fresenius Medical Care is also expected to grow in a low-single-digit percentage range in constant currency.

Without further acquisitions4, Fresenius projects an improvement of the net debt/EBITDA5 ratio (December 31, 2021: 3.51×6) into the self-imposed target corridor of 3.0x to 3.5x by the end of 2022. Fresenius expects the net debt/EBITDA ratio to slightly increase once the acquisitions of Ivenix and the majority stake in mAbxience are closed.

The Group’s cost and efficiency program is evolving according to plan and Fresenius confirms its increased savings targets provided in February 2022 of at least €150 million p.a. after tax and minority interest in 2023. For the years thereafter, a further significant increase in sustainable cost savings is expected.

1 FY/21 base: €37,520 million
2 Net income attributable to shareholders of Fresenius SE & Co. KGaA
3 FY/21 base: €1,867 million; before special items; FY/22: before special items
4 Cut-off date 22 February 2022
5 At LTM average exchange rates for both net debt and EBITDA; pro forma closed acquisitions/divestitures;
excluding further potential acquisitions; before special items; including lease liabilities
6 At LTM average exchange rates for both net debt and EBITDA; pro forma closed acquisitions/divestitures;
before special items; including lease liabilities

For a detailed overview of special items please see the reconciliation tables on pages 18-19 in the PDF.

Assumptions for guidance FY/22
COVID-19 will continue to impact Fresenius’ operations in 2022. Fresenius expects COVID-19 case numbers to decline going forward and consequently the number of elective treatments and staff availability to improve. An unlikely but possible significant deterioration of the situation triggering containment measures that could have a significant and direct impact on the health care sector without any appropriate compensation is not reflected in the Group’s FY/22 guidance.

The war in Ukraine is affecting Fresenius Group’s operations. The adverse effect of the war amounted to €14 million at net income level of Fresenius Group in the first quarter and is treated as a special item. Fresenius will continue to monitor closely the potential effects of the war.

With the increased uncertainty and volatility related to the Ukraine war, Fresenius now expects more pronounced cost inflationary effects and supply chain disruptions in 2022.

The Management Board assumes an unchanged corporate tax rate in the United States.

Furthermore, the assumptions for Fresenius Medical Care’s FY/22 guidance are also fully applicable to Fresenius Group’s FY/22 guidance.

All of these assumptions are subject to considerable uncertainty.

The recently announced acquisitions of Ivenix and the majority stake in mAbxience as well as any further potential acquisitions are excluded from guidance.

5% sales increase in constant currency
Group sales increased by 8% (5% in constant currency) to €9,720 million (Q1/21: €8,984 million). Organic growth was 3%. Acquisitions/divestitures contributed net 2% to growth. Currency translation increased sales growth by 3%. Excluding estimated COVID-19 effects1, Group sales growth would have been 5% to 6% in constant currency (Q1/21: 4% to 5%).

3% net income2,3 growth in constant currency
Group EBITDA before special items increased by 2% (-2% in constant currency) to €1,658 million (Q1/212: €1,631 million). Reported Group EBITDA was €1,595 million (Q1/21: €1,628 million).

Group EBIT before special items decreased by 1% (-5% in constant currency) to €996 million (Q1/212: €1,009 million) driven by the COVID-19-related excess mortality among Fresenius Medical Care’s patients as well as elevated labor, material and logistic costs. The EBIT margin before special items was 10.2% (Q1/212: 11.2%). Reported Group EBIT was €902 million (Q1/21: €1,006 million).

Group net interest before special items improved to -€119 million (Q1/212: -€137 million) mainly due to successful refinancing activities. Reported Group net interest also improved to -€118 million (Q1/21: -€137 million).

Group tax rate before special items was 22.7% (Q1/212: 22.8%) while the reported Group tax rate was 23.6% (Q1/21: 22.8%).

Noncontrolling interests before special items were -€216 million (Q1/212: -€237 million) of which 88% were attributable to the noncontrolling interests in Fresenius Medical Care. Reported noncontrolling interests were -€186 million (Q1/21: -€236 million).

1 For estimated COVID-19 effects in Q1/22 and Q1/21 please see table on page 16 in the PDF.
2 Before special items
3 Net income attributable to shareholders of Fresenius SE & Co. KGaA

For a detailed overview of special items please see the reconciliation tables on pages 18-19 in the PDF.

Group net income1 before special items increased by 6% (3% in constant currency) to €462 million (Q1/212: €436 million). Excluding estimated COVID-19 effects3, Group net income1 before special items would have been broadly stable (-2% to 2% in constant currency (Q1/21: 0% to 4%)). Reported Group net income1 decreased to €413 million (Q1/21: €435 million).

Earnings per share1 before special items increased by 6% (3% in constant currency) to €0.83 (Q1/212: €0.78). Reported earnings per share1 were €0.74 (Q1/21: €0.78).

Continued investment in growth
Spending on property, plant and equipment was €338 million corresponding to 3% of sales (Q1/21: €384 million; 4% of sales). These investments served primarily for the modernization and expansion of dialysis clinics, production facilities as well as hospitals and day clinics.

Total acquisition spending was €162 million (Q1/21: €149 million), mainly for the acquisition of dialysis clinics by Fresenius Medical Care and hospitals by Helios Spain.

Cash flow development
Group operating cash flow decreased to €101 million (Q1/21: €652 million) with a margin of 1.0% (Q1/21: 7.3%), mainly driven by working capital build-up from higher raw material inventories and receivables, among others, as well as phasing effects. Free cash flow before acquisitions and dividends decreased to -€255 million (Q1/21: €241 million). Free cash flow after acquisitions and dividends decreased to -€403 million (Q1/21: €117 million).

1 Net income attributable to shareholders of Fresenius SE & Co. KGaA
2 Before special items
3 For estimated COVID-19 effects in Q1/22 and Q1/21 please see table on page 16 in the PDF.

For a detailed overview of special items please see the reconciliation tables on pages 18-19 in the PDF.

Solid balance sheet structure
Group total assets increased by 2% (0% in constant currency) to €73,114 million (Dec. 31, 2021: €71,962 million) given currency translation effects and the expansion of business activities. Current assets increased by 3% (2% in constant currency) to €18,002 million (Dec. 31, 2021: €17,461 million), mainly driven by the increase of trade accounts receivables. Non-current assets increased by 1% (0% in constant currency) to €55,112 million (Dec. 31, 2021: €54,501 million).

Total shareholders’ equity increased by 4% (3% in constant currency) to €30,584 million (Dec. 31, 2021: €29,288 million). The equity ratio was 41.8% (Dec. 31, 2021: 40.7%).

Group debt remained stable (0% in constant currency) at €27,211 million (Dec. 31, 2021: € 27,155 million). Group net debt increased by 3% (2% in constant currency) to € 25,134 million (Dec. 31, 2021: € 24,391 million).

As of March 31, 2022, the net debt/EBITDA ratio increased to 3.60×1,2 (Dec. 31, 2021: 3.51×1,2) mainly driven by COVID-19 effects weighing on operating cash flow.

1 At LTM average exchange rates for both net debt and EBITDA; pro forma closed acquisitions/divestitures
2 Before special items

For a detailed overview of special items please see the reconciliation tables on pages 18-19 in the PDF.

Business Segments

Fresenius Medical Care (Financial data according to Fresenius Medical Care press release)

Fresenius Medical Care is the world’s largest provider of products and services for individuals with renal diseases. As of March 31, 2022, Fresenius Medical Care was treating 343,493 patients in 4,153 dialysis clinics. Along with its core business, the Renal Care Continuum, the company focuses on expanding in complementary areas and in the field of critical care.

• Higher than anticipated COVID-19-related excess mortality, but declining throughout the quarter
• Earnings development affected by ongoing significantly elevated labor costs compounded by effects from Omicron in Health Care Services and by increased material and logistic costs in Health Care Products
• Earnings development in EMEA additionally impacted by the war in Ukraine

Sales increased by 8% (3% in constant currency) to €4,548 million (Q1/21: €4,210 million). Organic growth was 2%. Currency translation increased sales growth by 5%.

EBIT decreased by 27% (-30% in constant currency) to €348 million (Q1/21: €474 million) resulting in a margin of 7.6% (Q1/21: 11.3%). EBIT before special items, i.e. costs incurred for FME25 and the impact related to the war in Ukraine, decreased by 15% (-19% in constant currency) to €403 million (Q1/21: €477 million), resulting in a margin1 of 8.9% (Q1/21: 11.3%). At constant currency, the decline was mainly due to higher labor costs, adverse COVID-19-related effects, as well as inflationary and supply chain cost increases. These effects were only partially mitigated by the partial reversal of an accrual related to a revenue recognition adjustment for accounts receivable in legal dispute.

1 Before special items
2 Net income attributable to shareholders of Fresenius Medical Care AG & Co. KGaA

For a detailed overview of special items please see the reconciliation tables on pages 18-19 in the PDF.

Net income1 decreased by 37% (-39% in constant currency) to €157 million (Q1/21: €249 million). Net income1 before special items decreased by 20% (-23% in constant currency) to €200 million (Q1/21: €251 million) mainly due to the mentioned negative effects on operating income.

Operating cash flow was €159 million (Q1/21: €208 million) with a margin of 3.5% (Q1/21: 4.9%). The decrease was mainly due to continued recoupment of the U.S. government’s payments received in 2020 under the CARES Act and a decrease in net income, partially offset by a favorable impact from trade accounts and other receivables.

For FY/22, Fresenius Medical Care confirms its outlook and expects revenue2 and net income1,3 to grow at low- to mid-single-digit percentage rates in constant currency4.

For further information, please see Fresenius Medical Care’s press release at View Source

1 Net income attributable to shareholders of Fresenius Medical Care AG & Co. KGaA
2 FY/21 base: €17,619 million
3 FY/21 base: €1,018 million, before special items; FY/22 before special items
4 These targets are based on the 2021 results excluding the costs related to FME25 of €49 million (for net income). They are based on the assumptions outlined in the press release on the Q4 and FY 2021 results (Feb.22, 2022), in constant currency and exclude special items. Special items include further costs related to FME25, the impacts related to the war in Ukraine, and other effects that are unusual in nature and have not been foreseeable or not foreseeable in size or impact at the time of giving guidance.

Schrödinger Reports First Quarter 2022 Financial Results

On May 4, 2022 Schrödinger, Inc. (Nasdaq: SDGR), whose physics-based software platform is transforming the way therapeutics and materials are discovered, reported financial results for the first quarter of 2022 (Press release, Schrodinger, MAY 4, 2022, View Source [SID1234613518]).

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"We began 2022 with a strong quarter, which included software revenue of $33.1 million, a 26 percent increase over the first quarter of 2021, driven primarily by continued adoption and scale up by existing customers," said Ramy Farid, Ph.D., chief executive officer of Schrödinger. "We are also seeing continued progress across our collaborative and internal drug discovery pipeline, further demonstrating the impact of our platform. Last month, we presented preclinical data from our Wee1 program, which highlighted our opportunity to advance a potential best-in-class Wee1 inhibitor into the clinic. We are working rapidly to progress our three most advanced internal programs into clinical development and are on track to submit an investigational new drug application for our MALT1 inhibitor, SGR-1505, to the FDA in the first half of 2022."

Strategic Objectives and Recent Business Highlights

In February 2022, Schrödinger laid out several strategic objectives for 2022-2023. Recent highlights include the following:

Internal Pipeline

Schrödinger is on track to submit an investigational new drug (IND) application to the U.S. Food and Drug Administration (FDA) for SGR-1505, its MALT1 inhibitor, in the first half of 2022. The company continues to plan to initiate a Phase 1 clinical study of SGR-1505 in patients with relapsed and resistant lymphoma in the second half of 2022. MALT1 is considered a potential therapeutic target for several non-Hodgkin’s B-cell lymphomas.

In April, Schrödinger presented new preclinical data from its Wee1 inhibitor program at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. These data underscore the therapeutic potential of Schrödinger’s Wee1 inhibitors for use as monotherapy and as part of combination therapy with other agents. Wee1 is emerging as a potentially important therapeutic target for a range of solid tumors, including ovarian and uterine cancer. Schrödinger continues to expect to select a Wee1 development candidate this year.

The company continues to advance its CDC7 development candidate through IND-enabling studies and expects to submit an IND to the FDA in early 2023. Targeting proteins such as CDC7 that play important roles in DNA replication and replication stress is gaining momentum as a new therapeutic approach based on the proliferative capacity of cancer cells to bypass DNA damage responses.

Schrödinger also continues to advance multiple undisclosed research programs in the areas of oncology and immunology.

Collaborative Programs

In March 2022, Morphic Therapeutic announced the initiation of a Phase 2a clinical study of MORF-057 in patients with moderate to severe ulcerative colitis. MORF-057 is a potent and selective, oral small molecule inhibitor of the α4β7 integrin being studied in patients with gastrointestinal disorders, initially targeting inflammatory bowel disease.

Materials Science

Today, Schrödinger announced that it recently entered into a three-year collaboration with Eonix LLC to accelerate the discovery and design of materials for safer, energy dense lithium ion batteries. As part of the agreement, Schrödinger received an equity stake in Eonix.

Underlying Science

During the first quarter, Schrödinger scientists continued to make scientific advances and were authors on 11 publications in peer-reviewed life sciences and materials science journals. Recent publications include reporting a novel extension to our neural network interaction potentials to more accurately model charge-charge interactions. Schrödinger anticipates that these improvements may enable more predictive modeling of polarization effects, reactivity, and polymorph stability, among a number of other endpoints of high importance to drug discovery and materials design.

2022 Financial Outlook

As of May 4, 2022, Schrödinger maintained the following expectations for the fiscal year ending December 31, 2022:

Total revenue expected to range from $161 million to $181 million, representing 17 percent to 31 percent growth over 2021

Total software revenue expected to range from $126 million to $136 million, representing 11 percent to 20 percent growth over 2021

Total drug discovery revenue expected to range from $35 million to $45 million, representing 42 to 82 percent growth over 2021

Operating expense growth is expected to be slightly lower than the 42 percent reported for the year ended December 31, 2021

Software gross margin percentage is expected to be in the mid-70s

For the second quarter of 2022, software revenue is expected to range from $28 to $30 million.

Webcast and Conference Call Information

Schrödinger will host a conference call to discuss its first quarter 2022 financial results on Wednesday, May 4, 2022, at 4:30 p.m. ET. To participate in the live call, please dial (833) 727-9520 (domestic) or +1 (830) 213-7697 (international) and refer to conference ID 7896009. The webcast can also be accessed under "News & Events" in the investors section of Schrödinger’s website, View Source The archived webcast will be available on Schrödinger’s website for approximately 90 days following the event.

CRISPR Therapeutics to Present at the 2022 Bank of America Healthcare Conference

On May 4, 2022 CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, reported that members of its senior management team are scheduled to participate in the 2022 Bank of America Healthcare Conference on Wednesday, May 11, 2022, at 4:40 p.m. PT (Press release, CRISPR Therapeutics, MAY 4, 2022, View Source [SID1234613535]).

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A live webcast of the event will be available on the "Events & Presentations" page in the Investors section of the Company’s website at View Source A replay of the webcast will be archived on the Company’s website for 14 days following the presentation.