Aeglea BioTherapeutics Announces $45 Million Registered Direct Offering Priced at a Premium to Market

On May 5, 2022 Aeglea BioTherapeutics, Inc. (NASDAQ:AGLE), a clinical-stage biotechnology company developing a new generation of human enzyme therapeutics as innovative solutions for rare metabolic diseases, reported that it has entered into a securities purchase agreement with certain institutional investors providing for the purchase and sale of registered securities of the Company in a registered direct offering for gross proceeds to Aeglea of approximately $45 million, prior to deducting placement agent fees and estimated offering expenses (Press release, Aeglea BioTherapeutics, MAY 5, 2022, View Source [SID1234613699]). The financing includes participation from Bain Capital Life Sciences, LP, Great Point Partners, LLC, clients of Nantahala Capital Management, Sio Capital Management, LLC and other institutional investors.

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The financing includes 10,752,688 shares of the Company’s common stock at a price of $1.60 per share and pre-funded warrants to purchase 17,372,397 shares of common stock, at a price of $1.5999 per pre-funded warrant, which represents the per share offering price for the common stock less the $0.0001 exercise price for each pre-funded warrant. The offering is expected to close on or about May 9, 2022, subject to customary closing conditions.

JonesTrading Institutional Services LLC is acting as placement agent for the registered direct offering.

The shares of common stock and pre-funded warrants were offered pursuant to a shelf registration statement on Form S-3 (File No. 333-239706), which was declared effective by the United States Securities and Exchange Commission ("SEC") on July 14, 2020. The Company intends to use the proceeds from the offering, together with its existing cash resources, to fund the Company’s activities related to our ongoing Biologics License Application submission for pegzilarginase and its potential commercialization in the United States for patients with Arginase 1 Deficiency, advance the clinical development of AGLE-177 through its Phase 1/2 clinical trial and prepare for a potential Phase 3 trial for the treatment of patients with Homocystinuria, and to advance AGLE-325 for Cystinuria through IND-enabling activities, and the remainder to fund continued research and development, manufacturing, working capital and general corporate purposes. The Company expects the net proceeds from this offering, together with its existing cash, cash equivalents, and marketable securities, to fund operations through the second quarter of 2023.

A prospectus supplement relating to the shares of common stock will be filed by the Company with the SEC. When available, copies of the prospectus supplement, together with the accompanying prospectus, can be obtained at the SEC’s website at www.sec.gov or from JonesTrading Institutional Services LLC at [email protected].

Puma Biotechnology Reports First Quarter 2022 Financial Results

On May 5, 2022 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, reported that financial results for the first quarter ended March 31, 2022 (Press release, Puma Biotechnology, MAY 5, 2022, View Source [SID1234613714]). Unless otherwise stated, all comparisons are for the first quarter of 2022 compared to the first quarter of 2021.

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Product revenue, net consists entirely of revenue from sales of NERLYNX, Puma’s first commercial product. Product revenue, net in the first quarter of 2022 was $40.7 million, compared to product revenue, net of $45.8 million in the first quarter of 2021.

Based on accounting principles generally accepted in the United States (GAAP), Puma reported net loss of $3.4 million, or $0.08 per basic and diluted share, for the first quarter of 2022, compared to net income of $16.5 million, or $0.41 per basic share and $0.40 per diluted share, for the first quarter of 2021.

Non-GAAP adjusted net loss was $0.3 million, or $0.01 per basic and diluted share, for the first quarter of 2022, compared to non-GAAP adjusted net income of $22.4 million, or $0.56 per basic share and $0.55 per diluted share, for the first quarter of 2021. Non-GAAP adjusted net income excludes stock-based compensation expense. For a reconciliation of GAAP net income (loss) to non-GAAP adjusted net income (loss) and GAAP net income (loss) per share to non-GAAP adjusted net income (loss) per share, please see the financial tables at the end of this news release.

Net cash used in operating activities for the first quarter of 2022 was $26.9 million, compared to $15.7 million provided by operating activities in the first quarter of 2021. At March 31, 2022, Puma had cash, cash equivalents and marketable securities of $73.9 million, compared to cash, cash equivalents and marketable securities of $82.1 million at December 31, 2021.

"2021 was an important year for Puma as we made operational changes to maximize the efficiency of the Puma team and the environment with which we operate," said Alan H. Auerbach, Chairman, Chief Executive Officer and President of Puma. "We remain committed to increasing awareness of and access to NERLYNX as an option to reduce the risk of recurrence for patients battling HER2-positive breast cancer; the inclusion of NERLYNX in the updated NCCN guidelines is an important step to expanding the awareness and utilization of neratinib for high-risk patients."

Mr. Auerbach added, "We anticipate the following key milestones over the next 12 months: (i) reporting Phase II data from the cohort of patients in the SUMMIT basket trial of neratinib in HER2-mutated HR-positive breast cancer (H1 2022); (ii) reporting Phase II data from the cohort of patients in the SUMMIT basket trial of neratinib in HER2-mutated biliary tract cancer (H1 2022); (iii) reporting Phase II data from the cohort of patients in the SUMMIT basket trial of neratinib in non-small cell lung cancer patients with EGFR exon 18 mutations (H2 2022); (iv) conducting a pre-NDA meeting with the FDA to discuss the potential for an accelerated approval pathway of neratinib in HER2-mutated HR-positive breast cancer (H2 2022); (v) conducting a meeting with the FDA to discuss the potential for an accelerated approval pathway for neratinib in non-small cell lung cancer patients with EGFR exon 18 mutations who have previously been treated with an EGFR tyrosine kinase inhibitor (2022); (vi) reporting Phase II TBCRC-022 trial data from Cohort 4B and 4C of the combination of Kadcyla plus neratinib in patients with HER2-positive breast cancer with brain metastases who have previously been treated with Kadcyla (H2 2022); and (vii) reporting Phase II data from the SUMMIT trial of neratinib in cervical cancer patients with HER2 mutations (H2 2022)."

Revenue

Total revenue consists of product revenue, net from sales of NERLYNX, Puma’s first commercial product, license revenue from Puma’s sub-licensees and royalty revenue. For the first quarter ended March 31, 2022, total revenue was $45.7 million, of which $40.7 million was net product revenue and $5.0 million was royalty revenue. This compares to total revenue of $98.2 million in the first quarter of 2021, of which $45.8 million was net product revenue, $50.0 million was license revenue and $2.4 million was royalty revenue.

Operating Costs and Expenses

Total operating costs and expenses were $46.4 million for the first quarter of 2022, compared to $78.0 million for the first quarter of 2021.

Cost of Sales

Cost of sales was $10.8 million for the first quarter of 2022, compared to $29.6 million for the first quarter of 2021. Cost of sales in the first quarter of 2021 included $20.0 million for a termination fee paid to a former sub-licensee for the return of commercial rights to NERLYNX in Greater China, partially offset by higher royalties due on increased non-U.S partner sales.

Selling, General and Administrative Expenses

Selling, general and administrative expenses were $20.4 million for the first quarter of 2022, compared to $28.2 million for the first quarter of 2021. The $7.8 million decrease resulted primarily from decreases of approximately $3.1 million in professional fees and expenses, primarily related to a decrease in consulting costs for marketing and commercialization support; $2.9 million in payroll and related costs due to reduced headcount; and $1.4 million in stock-based compensation also due to reduced headcount.

Research and Development Expenses

Research and development expenses were $15.2 million for the first quarter of 2022, compared to $20.2 million for the first quarter of 2021. The $5.0 million decrease resulted primarily from decreases of $2.5 million in internal R&D costs related primarily to reduced payroll costs; $1.3 million in stock-based compensation due to the impact of headcount reductions in 2021; $0.7 million in consultants and contractors due to the close of the CONTROL study and the winding down of the SUMMIT study; and $0.5 million in clinical trial expenses due to reduced study costs as noted above.

Total Other Income (Expenses)

Total other expenses were $2.7 million for the first quarter of 2022, compared to total other expenses of $3.7 million for the first quarter of 2021. The $1.0 million decrease in other expenses resulted primarily from lower interest expense on the milestone installment payments to Pfizer as well as lower costs related to our outstanding debt.

Conference Call

Puma Biotechnology will host a conference call to report its first quarter 2022 financial results and provide an update on the Company’s business and outlook at 1:30 p.m. PDT/4:30 p.m. EDT on Thursday, May 5, 2022. The call may be accessed by dialing (866) 682-6100 (domestic) or (862) 298-0702 (international). Please dial in at least 10 minutes in advance and inform the operator that you would like to join the "Puma Biotechnology Conference Call." A live webcast of the conference call and presentation slides may be accessed on the Investors section of the Puma Biotechnology website at View Source A replay of the call will be available approximately one hour after completion of the call and will be archived on Puma’s website for 90 days.

Insilico Medicine expands synthetic lethality portfolio with nomination of a preclinical candidate targeting MAT2A for the treatment of MTAP-deleted cancers

On May 5, 2022 Insilico Medicine ("Insilico"), a clinical-stage end-to-end artificial intelligence (AI)-driven drug discovery company, reported that the company has nominated a preclinical candidate (PCC) targeting methionine adenosyltransferase 2A (MAT2A) from AI-designed molecules for the treatment of methylthioadenosine phosphorylase (MTAP)-deleted cancers (Press release, Insilico Medicine, MAY 5, 2022, View Source [SID1234613731]). The PCC is part of Insilico’s growing portfolio of synthetic lethality assets in development.

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MTAP deletion is one of the most common gene deletions seen in cancers including lung, bladder, and pancreatic cancer, and is associated with poor prognosis. MAT2A is defined as a synthetic lethality target in MTAP-deleted cancers and plays an essential role in producing S-adenosylmethionine (SAM), a molecule involved in cell function and survival. Inhibitors of MAT2A lead to a selective anti-proliferative effect on MTAP-deleted cancer cells by reducing the level of SAM to affect PRMT5-Dependent mRNA splicing, inducing DNA damage.

Insilico’s PCC is a potent and selective MAT2A inhibitor. It demonstrated excellent drug-likeness with good solubility and permeability, good activity at low doses in animal models, and a favorable safety profile in preclinical studies. Insilico is progressing the PCC in IND-enabling studies and anticipates IND filing in early 2023.

"Powered by AI, the MAT2A program team was able to discover the PCC molecule with high selectivity of MTAP-deleted cancer cells over wide-type cells, which we believe provides key differentiation compared to reported MAT2A inhibitors," said Feng Ren, PhD, Chief Scientific Officer of Insilico Medicine. "This is the second PCC in our growing synthetic lethality pipeline, and we are progressing the molecule in IND-enabling studies towards clinical trials for the treatment of MTAP-deleted cancers."

Insilico has built a strong portfolio of synthetic lethality assets supported by scientists with deep drug discovery expertise and its AI-driven small molecule design and generation engine, Chemistry42. The company announced its first synthetic lethality PCC, which targets USP1 for tumors with homologous recombination deficiency, in mid-April. Continuing this success, Insilico delivered the PCC for the MAT2A program approximately 12 months after its initiation.

"This PCC continues the expansion of our synthetic lethality portfolio, driven by our end-to-end AI drug discovery platform," said Insilico founder and CEO Alex Zhavoronkov, PhD. "With this latest discovery, we continue to utilize the power of AI to treat the most aggressive cancers with the highest unmet needs."

Insilico is developing a growing portfolio in frontier areas. In just over 12 months, it has delivered 7 PCCs, including AI-discovered therapeutics of novel targets with novel structures and AI-designed therapeutics of known targets with desired properties. It also successfully completed a Phase 0 microdose trial and entered a Phase I clinical trial with its first internally developed program for fibrosis.

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.