On October 26, 2022 Thermo Fisher Scientific Inc. (NYSE: TMO), the world leader in serving science, reported its financial results for the third quarter ended October 1, 2022 (Press release, Thermo Fisher Scientific, OCT 26, 2022, View Source [SID1234622400]).

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Third Quarter 2022 Highlights

Third quarter revenue was $10.68 billion.
Third quarter GAAP diluted earnings per share (EPS) was $3.79.
Third quarter adjusted EPS was $5.08.
Delivered very strong financial results in the third quarter, with 14% Core organic revenue growth and $0.44 billion of COVID-19 testing revenue.
Launched a range of high-impact innovative new products, including the Orbitrap Ascend Tribrid mass spectrometer, which offers new capabilities for quantification and characterization of proteins while delivering high throughput and ease of use for diagnostic and drug discovery applications, as well as the Thermo Scientific Arctis Cryo-Plasma Focused Ion Beam, an automated microscope that streamlines cryo-electron tomography research and provides insights into how proteins and other molecules operate within cells. We also advanced our diagnostic offerings with the CE-IVD certification of the Oncomine Dx Express Test and Oncomine Reporter Dx software, which are designed to run on our Ion Torrent Genexus Next-Generation Sequencing System to advance precision oncology testing.
Continued to strengthen our unique customer value proposition with two new facilities to expand our capacity and capabilities: in Chelmsford, Massachusetts, we expanded our capacity for purification resins used in the production of biologics for a number of diseases; and in Plainville, Massachusetts, we expanded our viral vector manufacturing capacity to support cell and gene therapies.
Advanced on our environmental, social and governance priorities, signing an agreement with Enel North America to source half of our U.S. electricity needs from renewable wind power, continuing to deliver on our emissions-reduction strategy.
"We delivered another quarter of excellent financial performance driven by our proven growth strategy and powered by our PPI Business System. Our strategic investments and innovative new product launches are further enhancing our unique customer value proposition and leading to continued share gain," said Marc N. Casper, chairman, president and chief executive officer of Thermo Fisher Scientific. "We saw broad-based strength across our businesses, including our new clinical research business, which is performing very well. Customers are excited about our expanded capabilities, the integration continues to progress smoothly, and the long-term synergies remain very compelling."

Casper added, "With a strong nine months behind us, we are on track to deliver another outstanding year."

Third Quarter 2022

Revenue for the quarter grew 14% to $10.68 billion in 2022. Organic revenue was 1% lower; acquisitions increased revenue by 20% and currency translation decreased revenue by 5%. Core organic revenue growth was 14%. COVID-19 testing revenue was $0.44 billion.

GAAP Earnings Results

GAAP diluted EPS in the third quarter of 2022 was $3.79, versus $4.79 in the same quarter last year. GAAP operating income for the third quarter of 2022 was $1.71 billion, compared with $2.28 billion in the year-ago quarter. GAAP operating margin was 16.0%, compared with 24.4% in the third quarter of 2021.

Non-GAAP Earnings Results

Adjusted EPS in the third quarter of 2022 was $5.08, versus $5.77 in the third quarter of 2021. Adjusted operating income for the third quarter of 2022 was $2.37 billion, compared with $2.78 billion in the year-ago quarter. Adjusted operating margin was 22.2%, compared with 29.8% in the third quarter of 2021.

Annual Guidance for 2022

The company will provide updated 2022 financial guidance during its earnings conference call this morning at 8:30 a.m. Eastern Time.

Use of Non-GAAP Financial Measures

Adjusted EPS, adjusted net income, adjusted operating income, adjusted operating margin, free cash flow, organic revenue growth and Core organic revenue growth are non-GAAP measures that exclude certain items detailed after the tables that accompany this press release, under the heading "Supplemental Information Regarding Non-GAAP Financial Measures." The reconciliations of GAAP to non-GAAP financial measures are provided in the tables that accompany this press release.

Conference Call

Thermo Fisher Scientific will hold its earnings conference call today, October 26, 2022, at 8:30 a.m. Eastern Time. To listen, dial (844) 200-6205 within the U.S. or (929) 526-1599 outside the U.S. The conference ID is 406803. You may also listen to the call live on our website, www.thermofisher.com, by clicking on "Investors." You will find this press release, including the accompanying reconciliation of non-GAAP financial measures and related information, in that section of our website under "Financials." An audio archive of the call will be available under "News & Events" through Friday, November 11, 2022.

On October 26, 2022 Aileron Therapeutics (Nasdaq: ALRN), a chemoprotection oncology company focused on fundamentally transforming the experience of chemotherapy for cancer patients, reported that detailed results from its completed Phase 1 study of ALRN-6924 in healthy volunteers at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) 2022 taking place in Barcelona October 26 – 28, 2022 (Press release, Aileron Therapeutics, OCT 26, 2022, View Source [SID1234622399]). The poster titled, "ALRN-6924 Induces Cell Cycle Arrest in Bone Marrow Stem Cells and Hair Follicles with Dose-Dependent Degree and Duration of Effects after a Single Infusion in Healthy Volunteers" (Poster #136) is also available in the Scientific Resources section of Aileron’s website linked here.

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ALRN-6924 is a first-in-class MDM2/MDMX dual inhibitor that is currently in development as a novel, selective chemoprotective agent for patients with p53-mutated cancer. The findings presented at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) conference, which showed that ALRN-6924 induced p53-mediated cell cycle arrest in bone marrow stem cells and hair follicles, demonstrate the potential of ALRN-6924 to prevent chemotherapy-induced neutropenia, thrombocytopenia, and anemia, as well as chemotherapy-induced alopecia.

"While we previewed some of these new findings from our now completed Phase 1 study of ALRN-6924 in healthy volunteers earlier this year, we’re pleased to present the comprehensive results at an international scientific conference," said Manuel Aivado, M.D., Ph.D., President and Chief Executive Officer at Aileron. "These results contribute to the substantial body of scientific evidence that we believe has reliably and reproducibly demonstrated ALRN-6924’s potential as a biomarker-driven chemoprotective agent, driving us to work diligently to address the significant impact chemotherapy-induced toxicities have on cancer patients’ treatment experience and outcomes."

ALRN-6924 is designed to activate p53, which in turn upregulates p21, a known inhibitor of the cell replication cycle, thereby inducing cell cycle arrest to protect normal, healthy cells from chemotherapy-induced damage. The Phase 1 study in healthy volunteers was conducted to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of ALRN-6924. Aileron previously presented data from the study showing that a 0.3 mg/kg and 0.6 mg/kg 1-hour intravenous (IV) ALRN-6924 infusion was well tolerated, and transiently upregulated p21 in human bone marrow cells with minimal signal for apoptosis (n=37; Voors-Pette et al., ESMO (Free ESMO Whitepaper) 2021).

In the new findings presented today, cell cycle arrest was directly measured in the bone marrow and hair follicles of an additional 41 females. ALRN-6924 was administered as a single 1-hour IV infusion or 3-minute bolus injection at 0.3, 0.6, or 0.9 mg/kg to cohorts of 3 to 9 subjects and compared to placebo. Plasma and serum samples were obtained to determine PK and levels of macrophage inhibitory cytokine-1 (MIC-1), a biomarker of p53 activation. Bone marrow was sampled 12 hours post-dose to directly measure cell cycle arrest by flow cytometry in CD34+, lineage-negative bone marrow stem cells. Occipital scalp skin was sampled by a 2 mm punch biopsy for p21 immunohistochemistry in hair follicles.

In addition to the cell cycle arrest findings, ALRN-6924 continued to demonstrate a favorable tolerability profile, with subjects experiencing only mild, transient adverse events (AEs), with nausea/vomiting as the most frequent related AE. The degree and duration of serum MIC-1 elevation was dose-dependent, indicating more durable p53 activation at higher ALRN-6924 doses. At 12 hours post-dose, the proportion of cycling bone marrow stem cells was significantly reduced at all dose levels. Blinded pathology review suggested ALRN-6924-dependent p21 induction in anagen-phase hair follicles. Safety profiles, PK and PD were similar for both the 3-minute bolus and 1-hour infusion, providing rationale for future development of ALRN-6924 bolus administration.

"These findings are particularly compelling as they support our selection of the 1.2 mg/kg dose for our ongoing Phase 1b trial in patients with p53-mutated breast cancer, as well as our evaluation of protection against both chemotherapy-induced neutropenia and alopecia in that trial," said Allen Annis, Ph.D., Senior Vice President, Research at Aileron. "Beyond informing the dose and schedule for our current trial evaluating ALRN-6924 in breast cancer patients being treated with docetaxel, doxorubicin and cyclophosphamide, or TAC, these results suggest this dosing regimen can be uniformly applied when developing ALRN-6924 as a chemoprotective agent with other chemotherapies and for patients with other p53-mutated cancer indications."

On October 26, 2022 United Therapeutics Corporation (Nasdaq: UTHR) reported that it will report its third quarter 2022 financial results before the market opens on Wednesday, November 2, 2022 (Press release, United Therapeutics, OCT 26, 2022, View Source [SID1234622398]).

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United Therapeutics will host a public webcast Wednesday, November 2, 2022, at 9:00 a.m. Eastern Time. The webcast will be accessible via United Therapeutics’ website at View Source A rebroadcast of the webcast will be available for one week and can be accessed at the same location.

On October 26, 2022 Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) reported that it will report third quarter 2022 financial results after the close of the U.S. financial markets on Monday, November 7, 2022 and will hold a conference call that same day beginning at 4:30 p.m. Eastern time (Press release, Ligand, OCT 26, 2022, View Source [SID1234622397]). Speakers on the call will include Ligand’s CEO John Higgins, President and COO Matt Korenberg and CFO Tavo Espinoza.

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On October 26, 2022 AstraZeneca reported that Positive high-level results from the CAPItello-291 Phase III trial showed that it’s capivasertib in combination with Faslodex (fulvestrant) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) versus placebo plus Faslodex in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-low or negative locally advanced or metastatic breast cancer, following recurrence or progression on or after endocrine therapy (with or without a CDK4/6 inhibitor) (Press release, AstraZeneca, OCT 26, 2022, View Source [SID1234622396]).

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The trial met both primary endpoints, improving PFS in the overall patient population and in a prespecified biomarker subgroup of patients whose tumours had qualifying alterations in the PIK3CA, AKT1 or PTEN genes. Although the overall survival (OS) data were immature at the time of the analysis, early data are encouraging. The trial will continue to assess OS as a key secondary endpoint.

The safety profile of capivasertib plus Faslodex was similar to that observed in previous trials evaluating this combination.

Breast cancer is the most common cancer worldwide, with an estimated 2.3 million patients diagnosed in 2020.1 Approximately 70% of breast cancer tumours are considered HR-positive and HER2-low or negative.2 Endocrine therapies are widely used for the treatment of HR-positive breast cancer, but many patients with advanced disease develop resistance to 1st-line CDK4/6 inhibitors and estrogen receptor-targeting therapies, underscoring the need for additional options.3

Nicholas Turner, MD, PhD, Professor of Molecular Oncology at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, London, UK, and principal investigator in the CAPItello-291 Phase III trial, said: "The CAPItello-291 Phase III trial results show capivasertib offers a clinically meaningful improvement in progression free survival for patients with HR-positive breast cancer. This potential new medicine could give people more time with their cancer under control, which is a priority for patients and their families."

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "These exciting data in an all-comers population indicate that capivasertib could become a new first-in-class treatment option for patients with HR-positive breast cancer. These patients often experience tumour progression on, or resistance to, available endocrine therapies for advanced disease and urgently need new therapies that extend the effectiveness of endocrine-based treatment approaches."

The data will be presented at a forthcoming medical meeting and shared with global health authorities.

AstraZeneca has a comprehensive portfolio of approved and potential new medicines in development for patients with breast cancer. In addition to these results, the Company is also announcing today results from the SERENA-2 Phase II trial of camizestrant, the next-generation oral selective estrogen receptor degrader (ngSERD) in advanced estrogen receptor (ER)-positive breast cancer.

Notes

HR-positive breast cancer
HR-positive breast cancer (expressing estrogen or progesterone receptors, or both), is the most common subtype of breast cancer, and the growth of HR-positive breast cancer cells is often driven by ER.2,4,5 Endocrine therapies that target ER-driven disease are widely used as 1st-line treatment for this form of breast cancer in the advanced setting, and often paired with cyclin-dependent kinase (CDK) 4/6 inhibitors. However, resistance to CDK4/6 inhibitors and current endocrine therapies develops in many patients with advanced disease and treatment options are limited.3 Optimising endocrine therapy and overcoming resistance for patients with ER-driven disease at all stages of treatment are active areas of focus for breast cancer research.

CAPItello-291
CAPItello-291 is a Phase III, double-blind, randomised trial that is part of a larger clinical programme focused on capivasertib, an investigational AKT (serine/threonine kinase) inhibitor. CAPItello-291 is evaluating the efficacy of capivasertib in combination with Faslodex versus placebo plus Faslodex for the treatment of locally advanced (inoperable) or metastatic HR-positive, HER2-low or negative breast cancer.

The global trial enrolled 708 adult patients with histologically confirmed HR-positive, HER2-low or negative breast cancer whose disease has recurred or progressed during or after aromatase inhibitor therapy, with or without a CDK4/6 inhibitor, and up to one line of chemotherapy for advanced disease. The trial has dual primary endpoints of PFS in the overall patient population and in a subgroup of patients whose tumours have qualifying alterations in the PIK3CA, AKT1 or PTEN genes. In the trial, approximately 40% of tumours had PI3K/AKT/PTEN alterations.

Capivasertib
Capivasertib is an investigational oral treatment currently in Phase III trials for the treatment of multiple subtypes of breast cancer, prostate cancer and a Phase II trial for haematologic malignancies. A potent, selective adenosine triphosphate (ATP)-competitive inhibitor of all three AKT isoforms (AKT1/2/3), capivasertib is being evaluated in combination with existing therapies in tumours harbouring alterations in the PI3K/AKT/PTEN pathway, and in tumours reliant on signalling via this pathway for survival. Capivasertib is dosed according to an intermittent schedule, which consists of four days on and three days off. This was chosen in early phase trials based on tolerability and the degree of target inhibition.

The capivasertib clinical research programme is investigating the safety and efficacy of capivasertib when used in combination with established treatment regimens.

Capivasertib was discovered by AstraZeneca subsequent to a collaboration with Astex Therapeutics (and its collaboration with the Institute of Cancer Research and Cancer Research Technology Limited).

AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology, AstraZeneca is starting to challenge, and redefine, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death.

AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment.

With Enhertu (trastuzumab deruxtecan), a HER2-directed ADC, AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive and HER2-low metastatic breast cancer and are exploring its potential in earlier lines of treatment and in new breast cancer settings.

In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines Faslodex (fulvestrant) and Zoladex (goserelin) and aims to reshape the HR-positive space with ngSERD and potential new medicine camizestrant as well as a potential first-in-class AKT kinase inhibitor, capivasertib. AstraZeneca is also collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan, in this setting.

PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has been studied in early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research Lynparza in metastatic breast cancer patients with an inherited BRCA mutation and are exploring new opportunities to treat these patients earlier in their disease.

To bring much-needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is testing immunotherapy Imfinzi (durvalumab) in combination with other oncology medicines, including Lynparza and Enhertu, evaluating the potential of capivasertib in combination with chemotherapy, and datopotamab deruxtecan.

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.