On October 30, 2022 GenesisCare, a leading provider of integrated cancer care globally, and Prelude Corporation (PreludeDx(TM)), a leader in molecular diagnostics and precision medicine, reported interim results from the AUSPREDICT registry (Press release, GenesisCare, OCT 30, 2022, https://www.prnewswire.com/news-releases/genesiscare-and-preludedxtm-present-compelling-australian-first-dcisionrt-study-interim-analysis-during-breast-cancer-awareness-month-45-change-in-treatment-recommendations-when-using-dcisionrt-301662105.html [SID1234622599]). Data presented at the Australasian International Breast Congress demonstrates a significant (45%) change in radiation therapy treatment recommendations1 when using the DCISionRT test, optimising management to prevent over and under treatment of Australian women with Ductal Carcinoma In Situ (DCIS).

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DCIS is a pre-invasive disease of the breast that may lead to invasive breast cancer if untreated.(2) After breast conserving surgery (BCS) for DCIS, radiation therapy is often used to minimise the risk of recurrence. DCISionRT(R)is a novel molecular test that assesses the 10-year risk of recurrence after BCS and if there would be a benefit to treating with radiation therapy. GenesisCare and PreludeDx formed a strategic partnership in 2021 to bring DCISionRT to Australia for the first time and establish the AUS-PREDICT registry to collect real-world data to further the development of precision medicine and decision tools globally.

The presentation, entitled Interim Analysis of the PREDICT Registry Australia: Changes in Treatment Recommendation for a Biologic Signature Predictive of Radiation Therapy (RT) Benefit in Patients with DCIS, studied 232 patients from Australia who had received the DCISionRT test following breastconserving surgery. Radiation therapy recommendation decreased by 70% in patients with a low risk DCISionRT score and increased 29% in patients with elevated risk scores.(1)

Leading Specialist Breast Surgeon and Director of Breast Cancer Services for Royal Melbourne and Royal Women’s Hospital, Melbourne, Professor Bruce Mann, said: "Historically, we have relied on clinical pathology, such as tumour grade and size, to determine treatment plans for patients with DCIS. This data demonstrates the integration of DCISionRT into clinical decision making has a substantial impact on RT recommendations and has the ability to prevent over and under treatment of DCIS patients."

Principal Investigator and GenesisCare Radiation Oncologist, Dr Yvonne Zissiadis, said the interim results "demonstrate the critical role of DCISionRT in the clinical treatment pathway for DCIS patients, ensuring women receive the right treatment at the right time. "Our study highlights that DCISionRT is a promising predictive tool, arming clinicians and patients with the information to make informed decisions about treatment options based on a patient’s individual biological risk profile."

"GenesisCare, in partnership with PreludeDx, is thrilled to present the interim findings from our Australian-first study," continued Dr Zissiadis.

"The first interim analysis of AUS-PREDICT is highly consistent with the US-PREDICT registry3 that has completed enrollment of 2,500 patients," said Troy Bremer, PhD, Chief Scientific Officer of PreludeDx. "In the registry studies in both countries, DCISionRT was the most impactful single factor for changing treatment recommendations regarding radiation therapy following breast conserving surgery," continued Dr. Bremer.

"We are delighted to bring precision medicine to Australian women diagnosed with DCIS and further enrollment in the AUS-PREDICT registry. We look forward to the continued expansion of our global data network and clinical evidence for DCISionRT," said Dan Forche, CEO of PreludeDx.

On October 30, 2022 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures, and commercializes high-quality medicines for the treatment of oncology, autoimmune, metabolic, ophthalmology and other major diseases, reported that the first patient was dosed in Australia for its proprietary anti-Claudin18.2 monoclonal antibody-drug conjugate(ADC) (R&D code: IBI343) in Phase I clinical trial for the treatment of patients with advanced solid tumors (Press release, Innovent Biologics, OCT 30, 2022, View Source [SID1234622598]). It is the first ADC candidate drug to enter clinical phase in Innovent’s pipeline.

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The study (NCT05458219) is an open-label, multi-center Phase I study evaluating the safety, tolerability, and preliminary efficacy of IBI343 in subjects with advanced solid tumors, and to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D).

IBI343 is a recombinant human anti-Claudin 18.2 monoclonal ADC. After IBI343 binds to the Claudin 18.2-expressing tumor cells, the Claudin 18.2 dependent ADC internalization occurred and the drug is released resulting in DNA damage and eventually apoptosis of the tumor cells. The freed drug can also diffuse across the plasma membrane to reach and kill the neighboring cells, resulting in "bystander killing effect". In both Claudin 18.2 high and low expression mice tumor bearing models, IBI343 exhibited potent tumor growth inhibition efficacy, and it also demonstrated tolerable safety profile in preclinical in vivo models.

Dr. Andrea Tazbirkova, Pindara Private Hospital Located in Queensland, Australia, stated： "Claudin 18.2 has emerged as an ideal anti-tumor target and has been clinically validated by different modalities including mono-antibodies and CAR-T therapy with manageable toxicity. Nonetheless, the efficacy is selective and limited within cancer patients with CLDN18.2-high expression, leaving unmet need for patients with CLDN18.2 low-expressing tumors. IBI343 is Claudin 18.2 targeting ADC with bystander effect and has demonstrated promising anti-tumor effect in Claudin 18.2-high and low in-vivo models with tolerable safety profile. We look forward to the positive results in the safety/tolerability and efficacy of IBI343 in the clinic."

Dr. Hui Zhou, Senior Vice President of Innovent, stated: " At present, target treatment options are limited for gastric and pancreatic cancer where imply huge unmet clinical needs. High expression of Claudin 18.2 in aforesaid tumors suggests its high potential and Innovent has been actively rolling out a cluster of Claudin 18.2 drug candidates across different modalities to seek for differentiated therapeutic values while guarantee druggability. We are pleased that the first patient dose of IBI343 has been completed in Australia. In parallel, the IND for IBI343 has been filed in China last month. We are looking forward to the positive results of IBI343 in patients with advanced solid tumors. IBI343 is our first ADC molecule to initiate clinical study in both Australia and China, adding a valuable clinical asset in our R&D pipeline that represents Innovent’s global innovation strategy. The company will also accelerate the development of more innovative molecules with high global potential, taking advantage of cross-regional R & D and clinical resources, adhering to the long-term development strategy of ‘driven by innovation, developed through globalization’with an aim to benefit cancer patients worldwide."

About Claudin 18.2

Claudin18.2 is a member of the Claudin protein family, which is a highly tissue-specific protein expressed only in differentiated epithelial cells on the gastric mucosa under normal physiological conditions. Previous studies have revealed that Claudin18.2 is highly expressed in multiple types of cancer such as gastric cancer, pancreatic cancer, esophageal adenocarcinoma, and colorectal cancer. The unique feature of limited expression in normal tissues and highly specific expression in cancer makes Claudin18.2 an ideal target for developing the immunotherapeutic for solid tumors.

Globally, there are many candidate therapies in clinical development. The drug modalities under development include monoclonal antibodies, bispecific antibodies, antibody-conjugated drugs and CAR-T cell products. However, currently no drug targeting Claudin18.2 has been approved.

About IBI343

IBI343 is a recombinant human anti-Claudin 18.2 monoclonal antibody-drug conjugate (ADC) developed by Innovent Biologics. IBI343 binds to the Claudin 18.2-expressing tumor cells, the Claudin 18.2 dependent ADC internalization will occurr and the drug is released resulting in DNA damage and eventually apoptosis of the tumor cells. The freed drug can also diffuse across the plasma membrane to reach and kill the neighboring cells, resulting in "bystander killing effect". Currently, Phase I study of IBI343 has been conducted in Australia (NCT05458219) to assess the safety, tolerability, and preliminary efficacy of IBI343 in subjects with advanced solid tumors, and to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D).

On October 30, 2022 Akeso, Biopharma (9926. HK) ("Akeso") reported the Phase Ib clinical results of Ivonescimab (PD-1/VEGF bi-specific, AK112) in combination with etoposide and carboplatin in first-line treatment of extensive-stage small-cell lung cancer(ES-SCLC), in an oral presentation at the IASLC 2022 Asia Conference on Lung Cancer (Press release, Akeso Biopharma, OCT 30, 2022, View Source [SID1234622597]).

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Preliminary data of AK112 combination with etoposide and carboplatin showed a favorable safety profile and promising anti-tumor efficacy as first-line treatment in patients with ES-SCLC and may be a promising treatment option. Compared to the data from marketed PD-L1 inhibitors in combination with chemotherapy, AK112 in combination with chemotherapy demonstrated superior antitumor efficacy and survival benefit.

As of June 1, 2022, all patients had received at least one dose of AK112. The median follow-up time was 7.2 months.

Median progression-free survival (PFS) was 6.9 months, with a 6-month PFS rate of 52.1%,
Objective remission rate (ORR) was 87.5%, and disease control rate (DCR) was 96.9%.
Overall survival (OS) data are not mature.
No new safety signal was observed.
Lung cancer is one of the most common cancers globally and in China, with up to two-thirds of SCLC patients having ES-SCLC at first diagnosis, and etoposide + platinum has been the standard of care for first-line treatment of ES-SCLC for more than 30 years. Two PD-L1 inhibitors have been approved in combination with chemotherapy to treat ES-SCLC, but the survival benefit for patients remains very limited.

Two Phase III trials of Ivonescimab for major lung cancer indications are currently being conducted efficiently, including Ivonescimab plus chemotherapy versus chemotherapy in EGFR mutated advanced non-squamous NSCLC that failed in prior EGFR-TKI therapy, and Ivonescimab monotherapy versus Pembrolizumab monotherapy as the first-line treatment for NSCLC patients with positive PD-L1 expression.

Related Studies:

Atelelizumab (PD-L1) in combination with carboplatin and etoposide, was approved for the first-line treatment of ES-SCLC (IMpower133) which had a median PFS of 5.2 months, a median OS of 12.3 months, and an ORR of 60.2%. [1] [2]

Dulvalizumab (PD-L1) in combination with etoposide and either carboplatin or cisplatin, was approved for the first-line treatment of ES-SCLC (CASPIAN) which had a median PFS of 5.1 months, an ORR of 68%, and a median OS of 13 months[3]

On October 30, 2022 Fresenius reported taht Over the past month, I’ve met with many of my Fresenius colleagues (Press release, Fresenius, OCT 30, 2022, View Source [SID1234622595]). Like me, they have tremendous passion and commitment to patients, physicians and health care professionals. What we do is life-saving."

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Sen continued, "Everyone at Fresenius knows we must improve on what we do. My priorities are clear: Reset the company aiming at becoming a stronger company and delivering value for our shareholders. Our businesses are growing yet in a more challenging environment. Now we sharpen our focus on structural productivity. More fundamentally, we have embarked on a top-to-bottom review of every business activity, looking at the entire corporate portfolio. The focus is on returns. This will not happen overnight, but we will move at a faster pace and more decisively than ever before. This will benefit all our stakeholders. This is #FutureFresenius."

Sen concluded, "Fresenius is a strong company, with great products, great market positions. Now we have to make it stronger."

FY/22 Group guidance
Since Fresenius Medical Care continues to operate in a challenging environment, the impacts of the Company’s focused efforts to improve North American Health Care Services operations are delayed against previous assumptions. Therefore, Fresenius Medical Care now assumes lower contributions in the financial year 2022.
Consequently, Fresenius Medical Care now expects net income (attributable to shareholders of Fresenius Medical Care AG & Co. KGaA) for the financial year 2022 to decline in the high teens to mid-twenties percentage range. The Company continues to anticipate revenue to grow at a low-single digit percentage range in the financial year 2022. These targets are in constant currency and exclude special items.

All other business segments of the Fresenius Group, in particular Vamed, are also affected by a challenging overall economic environment. Thus, there are increased uncertainties, inflation-related cost increases, staff shortages, disruptions in supply chains, and increased energy costs. This has a direct impact on customer and patient behavior.

However, as a consequence of the development at Fresenius Medical Care, Fresenius Vamed, and in view of increasing indications of a persistent unfavorable development of these and other factors for the further course of the financial year, the Management Board has changed its risk assessment and consequently also adjusted the Group outlook for FY/22.

At constant currency, the Company now anticipates Group net income1,2 to decline around ten percent (previously: decline in a low-to-mid single-digit percentage range). Group sales3 in constant currency continue to be expected to grow in a low-to-mid single-digit percentage range.

Without the closed acquisition of Ivenix and the completed acquisition of a majority stake in mAbxience as well as any further potential acquisitions, Fresenius expects the net debt/EBITDA4 ratio to be roughly on the same level as in Q3/22 (3.64×5) by the end of 2022 (December 31, 2021: 3.51×5).

1 Net income attributable to shareholders of Fresenius SE & Co. KGaA
2 FY/21 base: €1,867 million, before special items; FY/22: before special items
3 FY/21 base: €37,520 million
4 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
5 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 22-25 in the PDF.

Assumptions for guidance FY/22
For 2022 and beyond, Fresenius expects that the current challenging market environment and the global macro-economic headwinds will remain. In particular, the general cost inflation, labor shortages, meaningful uncertainty with regard to the future development of energy prices, burdens from supply chain disruptions and ongoing impacts of the COVID-19 pandemic are expected to continue. The guidance does not consider a significant disruption of gas or electricity supplies in Europe.

Fresenius will continue to closely monitor the potential further consequences of the overall heightened volatility and muted visibility, including balance sheet valuations.

The war in Ukraine is directly and indirectly affecting Fresenius Group operations. The direct adverse effects of the war amounted to €24 million at net income1 level of Fresenius Group in Q1-3/22 and are treated as a special item.

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.

For Fresenius Medical Care‘s contribution to the Group’s financial figures, 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 acquisitions of Ivenix and of the majority stake in mAbxience as well as any further potential acquisitions remain excluded from guidance.

1 Net income attributable to shareholders of Fresenius SE & Co. KGaA

5% sales increase in constant currency
Group sales increased by 12% (5% in constant currency) to €10,459 million (Q3/21: €9,324 million). Organic growth was 4%. Acquisitions/divestitures contributed net 1% to growth. Currency translation increased sales growth by 7%. Excluding estimated COVID-19 effects1, Group sales growth would have been 4% to 5% in constant currency (Q3/21: 7% to 8%).

In Q1-3/22, Group sales increased by 10% (4% in constant currency) to €30,197 million (Q1-3/21: €27,554 million). Organic growth was 3%. Acquisitions/divestitures contributed net 1% to growth. Currency translation increased sales growth by 6%. Excluding estimated COVID-19 effects1, Group sales growth would have been 3% to 4% in constant currency (Q1-3/21: 5% to 6%).

19% net income2,3,4 decline in constant currency
Group EBITDA before special items decreased by 2% (-10% in constant currency) to €1,662 million (Q3/212: €1,703 million). Reported Group EBITDA was €1,658 million (Q3/21: €1,667 million).

In Q1-3/22, Group EBITDA before special items remained nearly unchanged (-6% in constant currency) at €5,006 million (Q1-3/212: €5,008 million). Reported Group EBITDA was €4,781 million (Q1-3/21: €4,957 million).

Group EBIT before special items decreased by 9% (-17% in constant currency) to €949 million (Q3/212: €1,044 million). The decrease was mainly driven by higher labor costs at Fresenius Medical Care in the U.S., general cost inflation, revaluation of contract assets in the international service and project business at Fresenius Vamed as well as higher costs in the Corporate segment. The EBIT margin before special items was 9.1% (Q3/212: 11.2%). Reported Group EBIT was €887 million (Q3/21: €1,008 million).

In Q1-3/22, Group EBIT before special items decreased by 4% (-10% in constant currency) to €2,952 million (Q1-3/212: €3,086 million). The EBIT margin before special items was 9.8% (Q1-3/212: 11.2%). Reported Group EBIT was €2,634 million (Q1-3/21: €3,035 million).

1 For estimated COVID-19 effects please see table on page 20.
2 Before special items
3 Net income attributable to shareholders of Fresenius SE & Co. KGaA
4 Excluding Ivenix and mAbxience acquisitions

For a detailed overview of special items please see the reconciliation tables on pages 22-25 in the PDF.

Group net interest before special items was -€141 million (Q3/211: -€126 million) mainly due to currency translation effects and overall higher interest rates. Reported Group net interest decreased to -€141 million (Q3/21: -€126 million).

In Q1-3/22, Group net interest before special items improved to -€376 million (Q1-3/211: -€384 million). Reported Group net interest improved to -€375 million (Q1-3/21: -€384 million).

Group tax rate before special items was 25.0% (Q3/211: 22.9%) mainly due to an increase in the proportionate share of non-tax-deductible expenses compared to taxable income at Fresenius Medical Care. Reported Group tax rate was 26.1% (Q3/21: 22.8%). In Q1-3/22, Group tax rate before special items was 23.5% (Q1-3/211: 22.4%) while the reported Group tax rate was 24.1% (Q1-3/21: 22.3%).

Noncontrolling interests before special items were -€235 million (Q3/211: -€273 million) of which 90% were attributable to the noncontrolling interests in Fresenius Medical Care. Reported noncontrolling interests were -€230 million (Q3/21: -€268 million).
In Q1-3/22, Noncontrolling interests before special items were -€686 million (Q1-3/211: -€751 million) of which 89% were attributable to the noncontrolling interests in Fresenius Medical Care. Reported noncontrolling interests were -€597 million (Q1-3/21: -€741 million).

Group net income2 before special items decreased by 15% (-22%/-19%3 in constant currency) to €371 million (Q3/211: €435 million). The decrease was mainly driven by higher labor costs at Fresenius Medical Care in the U.S., general cost inflation, revaluation of contract assets in the international service and project business at Fresenius Vamed as well as higher costs in the Corporate/Other segment. Moreover, increased interest expenses and a higher tax rate had a negative effect on Group net income. Excluding estimated COVID-19 effects4, Group net income2 before special items was -26% to -22% in constant currency (Q3/21: 12% to 16%). Reported Group net income2 decreased to €321 million (Q3/21: €413 million).

In Q1-3/22, Group net income2 before special items decreased by 5% (-10%/-8%3 in constant currency) to €1,284 million (Q1-3/211: €1,346 million). Excluding estimated COVID-19 effects4, Group net income2 before special items was -15% to -11% in constant currency (Q1-3/21: 7% to 11%). Reported Group net income2 decreased to €1,117 million (Q1-3/21: €1,319 million).

1 Before special items
2 Net income attributable to shareholders of Fresenius SE & Co. KGaA
3 Excluding Ivenix and mAbxience acquisitions
4 For estimated COVID-19 effects please see table on page 20

For a detailed overview of special items please see the reconciliation tables on pages 22-25 in the PDF.

Earnings per share1 before special items decreased by 15% (-22% in constant currency) to €0.66 (Q3/212: €0.78). Reported earnings per share1 were €0.57 (Q3/21: €0.74).

In Q1-3/22, earnings per share1 before special items decreased by 5% (-10% in constant currency) to €2.29 (Q1-3/212: €2.41). Reported earnings per share1 were €1.99 (Q1-3/21: €2.36).

Continued investment in growth
Spending on property, plant and equipment was €416 million corresponding to 4% of sales (Q3/21: €449 million; 5% of sales). These investments served primarily for the modernization and expansion of dialysis clinics, production facilities as well as hospitals and day clinics. In Q1-3/22, spending on property, plant and equipment was €1,173 million corresponding to 4% of sales (Q1-3/21: €1,342 million; 5% of sales).

Total acquisition spending was €502 million (Q3/21: €167 million), mainly for the majority stake in mAbxience by Fresenius Kabi. In Q1-3/22, total acquisition spending was €955 million (Q1-3/21: €807 million).

Cash flow development
Group operating cash flow increased to €1,256 million (Q3/21: €1,226 million) with a margin of 12.0% (Q3/21: 13.1%). Free cash flow before acquisitions and dividends increased to €876 million (Q3/21: €793 million). Free cash flow after acquisitions and dividends decreased to €388 million (Q3/21: €594 million).

In Q1-3/22, Group operating cash flow decreased to €2,374 million (Q1-3/21: €3,329 million) with a margin of 7.9% (Q1-3/21: 12.1%). Free cash flow before acquisitions and dividends decreased to €1,202 million (Q1-3/21: €1,986 million). Free cash flow after acquisitions and dividends decreased to -€406 million (Q1-3/21: €352 million).

Solid balance sheet structure
Group total assets increased by 12% (4% in constant currency) to €80,328 million (Dec. 31, 2021: €71,962 million) given currency translation effects, acquisitions and the expansion of business activities. Current assets increased by 11% (6% in constant currency) to €19,443 million (Dec. 31, 2021: €17,461 million), mainly driven by the increase of trade accounts receivables and inventories. Non-current assets increased by 12% (4% in constant currency) to €60,885 million (Dec. 31, 2021: €54,501 million).

Total shareholders’ equity increased by 17% (6% in constant currency) to €34,156 million (Dec. 31, 2021: €29,288 million). The equity ratio was 42.5% (Dec. 31, 2021: 40.7%).

Group debt increased by 5% (1% in constant currency) at €28,607 million (Dec. 31, 2021: € 27,155 million). Group net debt increased by 9% (4% in constant currency) to € 26,479 million (Dec. 31, 2021: € 24,391 million).

As of September 30, 2022, the net debt/EBITDA ratio was 3.74×1,2 (Dec. 31, 2021: 3.51×1,2) mainly driven by lower EBITDA contribution as well as acquisition spending. The net debt/EBITDA as of September 30, 2022 excluding the closed acquisition of Ivenix and the completed acquisition of a majority stake in mAbxience was 3.641,2.

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 22-25 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 September 30, 2022, Fresenius Medical Care was treating 344,593 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.

Business development continues to be strongly impacted by uncertain inflationary macroeconomic environment
Impacts of improvements in North American Health Care Services operations delayed
COVID-19-related excess mortality in line with expectations
Important step in value-based care achieved with closing of InterWell Health merger
Sales increased by 15% (3% in constant currency) to €5,096 million (Q3/21: €4,441 million). Organic growth was 2%. Currency translation increased sales growth by 12%. In Q1-3/22, sales increased by 11% (2% in constant currency) to €14,401 million (Q1-3/21: €12,972 million). Organic growth was 1%. Currency translation increased sales growth by 9%.

EBIT decreased by 7% (-17% in constant currency) to €472 million (Q3/21: €505 million) resulting in a margin of 9.3% (Q3/21: 11.4%). EBIT before special items decreased by 8% (-18% in constant currency) to €470 million (Q3/21: €513 million), resulting in a margin1 of 9.2% (Q3/21: 11.6%). At constant currency, the decline was mainly due to higher labor costs as well as inflationary and supply chain cost increases. This was partially offset by €80 million (Q3 2021: €0.3 million) of Provider Relief Funding from the U.S. government to compensate for certain COVID-19-related costs. In Q1-3/22, EBIT decreased by 17% (-24% in constant currency) to €1,160 million (Q1-3/21: €1,403 million) resulting in a margin of 8.1% (Q1-3/21: 10.8%). EBIT before special items decreased by 7% (-14% in constant currency) to €1,322 million (Q1-3/21: €1,423 million), resulting in a margin1 of 9.2% (Q1-3/21: 11.0%).

Net income2 decreased by 16% (-24% in constant currency) to €230 million (Q3/21: €273 million). Net income2 before special items decreased by 17% (-25% in constant currency) to €231 million (Q3/21: €280 million). Besides the above-mentioned effects on operating income, the constant currency decline was mainly due to an increase in the proportionate share of non-tax-deductible expenses compared to taxable income.

In Q1-3/22, net income2 decreased by 28% (-34% in constant currency) to €535 million (Q1-3/21: €741 million). Net income2 before special items decreased by 13% (-18% in constant currency) to €660 million (Q1-3/21: €756 million).

Operating cash flow was €658 million (Q3/21: €692million) with a margin of 12.9% (Q3/21: 15.6%). The decrease was mainly due to lower net income. In Q1-3/22, operating cash flow was €1,568 million (Q1-3/21: €1,820 million) with a margin of 10.9% (Q1-3/21: 14.0%).

Based on the delayed impacts of improvements in North American Health Care Services operations, the continuously challenging and uncertain macroeconomic environment, and the results for the third quarter, which had a more pronounced support by one-time effects, Fresenius Medical Care, as a matter of caution, extends its 2022 guidance range for net income2,3 decline from a high-teens to a high-teens to mid-twenties percentage range. The Company confirms its target for revenue4 to grow at a low single digit percentage rate in full year 2022. Revenue and net income guidance are both on a constant currency basis and excluding special items5.

1 Before special items
2 Net income attributable to shareholders of Fresenius Medical Care AG & Co. KGaA
3 FY/21 base: €1,018 million, before special items; FY/22 before special items
4 FY/21 base: €17,619 million
5 These targets are based on the 2021 results excluding the costs related to FME25 of EUR 49 million (for Net Income). They are in constant currency and exclude special items. Special items include further costs related to FME25, the impact of the war in Ukraine, the impact of hyperinflation in Turkiye, the Humacyte investment remeasurement, the net gain related to InterWell Health 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.

For a detailed overview of special items please see the reconciliation tables on pages 22-25 in the PDF.

InterWell Health merger closed
With the closing of the three-way merger of Fresenius Health Partners, InterWell Health and Cricket Health, a premier value-based kidney care provider has been created in the U.S. This is an important step in the execution of Fresenius Medical Care’s strategy. The new company operates under the InterWell Health brand and will be fully consolidated by Fresenius Medical Care as the majority owner. The closing of the merger resulted in a net gain of €56 million (on EBIT level) in the third quarter, which is treated as a special item.

On October 28, 2022 Patrys Limited (ASX: PAB, "Patrys" or the "Company"), a therapeutic antibody development company, reported its Quarterly Activities Report and Appendix 4C Quarterly Cash Flow report for the quarter ended 30 September 2022 (Press release, Patrys, OCT 28, 2022, View Source [SID1234623643]).

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Patrys Chief Executive Officer and Managing Director, Dr. James Campbell said: "We are delighted that the second engineering run has provided us with the material needed to complete the final studies that will allow us to initiate the first clinical trials of PAT-DX1 in the second half of next year. This is a very significant milestone for the company. The preclinical work on our deoxymabs continues to highlight the great potential these unique antibodies have to provide new therapeutic approaches for treating cancer. In addition to the exciting results reported from the Telethon Kids Cancer Centre, we are very pleased that additional grant funding has been secured to continue the research that is being conducted at the Olivia Newton John Cancer Research Institute looking at ways to use our deoxymabs to treat breast cancers."

Operations Update
At the beginning of the quarter, Patrys announced that its Contract Development Manufacturing Organisation (CDMO) had completed a second engineering run of PAT-DX1 which used an updated purification process to produce large-scale quantities of clinical grade PAT-DX1. In August, Patrys reported that the material produced in this engineering run had successfully completed specification testing. Specification testing is a necessary requirement to ensure that the activity and purity of the manufactured drug material falls within pre-defined tolerance levels. The PAT-DX1 drug material has also undergone microbiological and chemical testing to confirm the absence of contaminants. For personal use only 2 This GMP PAT-DX1 drug material will be used to complete the two remaining animal toxicology studies that are required before first-in-human studies can be initiated in 2H CY2023. Patrys has already successfully completed animal toxicology studies using non-GLP PAT-DX1 drug material and these showed that it is safe and well-tolerated. The GLP toxicology studies for PAT-DX1 are scheduled to commence in Q4 CY2022.

In August, Patrys reported new pre-clinical data for its lead asset, PAT-DX1 which supports the development of PAT-DX1 as a potential treatment for high grade glioma (HGG), a fast growing and clinically challenging form of brain cancer. The study was conducted in the laboratory of Professor Terrence Johns of the Telethon Kids Cancer Centre as part of the program of research being conducted under the $250,000 grant from the inaugural Clinical Accelerator fund of the Cure Brain Cancer Foundation awarded earlier this year.

In this study, the administration of PAT-DX1 increased the effectiveness of radiation therapy which resulted in a significant improvement in survival in an animal model of high-grade glioma Researchers at the Olivia Newton-John Cancer Research Institute (ONJCRI) have been awarded a $100,000 Victorian Medical Research Acceleration Fund (VMRAF) grant from the Victorian State Government to support research into the potential to incorporate PAT-DX1 and PAT-DX3 into new treatments for metastatic breast cancer. This research program will be led by Professor Robin Anderson, Head of ONJCRI’s Translational Breast Cancer Program and Metastasis Research Laboratory. Professor Anderson’s research is focused on understanding the genetic regulation of metastasis, primarily in breast cancer, and is aimed at identifying new targets for molecular based therapy for patients with progressive disease.

Corporate Update In August, John Read announced his intention to step down as Chair of Patrys having held the role since the company listed on the ASX approximately 15 years ago. Mr Read played a pivotal leadership role, most recently guiding the Company’s development of its unique deoxymab antibody technology platform. Current Director Mike Stork has been appointed as interim Chair while a search for a permanent Chair is completed. While this is being undertaken, Stefan Ross has been appointed as a Non-Executive Director and it is intended that he will step down from this position once a permanent Chair is appointed. In September Patrys and Hefei Co-Source mutually agreed to terminate the exclusive development and commercialisation program for China for the IgM asset PAT-SC1, which was the last of Patrys’ IgM legacy assets.

The termination of this program aligns with Patrys’ focus on advancing its deoxymab technology towards the clinic. During the quarter ended 30 September 2022, Patrys had net cash outflows from operating activities of A$2,584k, with A$2,151k invested in R&D activities. At 30 September 2022, Patrys held A$5.2M in cash and an additional A$2M in short-term investments. Payments to related parties and their associates during the quarter, which are outlined in Section 6 of the accompanying Appendix 4C to this For personal use only 3 quarterly activity report, were A$166k. These payments include non-executive director fees and consulting services as well as salary (including superannuation) for the CEO and Managing Director.