Morphic Announces Corporate Highlights and Second Quarter 2021 Financial Results

On August 4, 2021 Morphic Therapeutic (Nasdaq: MORF), a biopharmaceutical company developing a new generation of oral integrin therapies for the treatment of serious chronic diseases, reported corporate highlights and financial results for the second quarter of 2021 (Press release, Morphic Therapeutic, AUG 4, 2021, View Source [SID1234585675]).

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Recent Highlights and Outlook

Presented positive phase 1 data fully supporting MORF-057 target product profile at the European Crohn’s and Colitis Organisation (ECCO) Virtual Congress 2021

MORF-057 well tolerated at all doses (25 to 400 mg), no safety signals observed
Predictable and dose-dependent pharmacokinetics (PK) surpassing preclinical modeling
Pharmacodynamic (PD) results strongly supportive of MORF-057 continued clinical development

Dose and time dependent α4β7 receptor occupancy including receptor saturation in all subjects at 100 mg BID
Biomarker changes, including lymphocyte subset migration and CCR9 transcript levels, provide early proof of biology
Changes in lymphocyte subsets and CCR9 levels are consistent with published literature on intravenous integrin inhibitors in inflammatory bowel disease (IBD), despite the brief 14-day duration of exposure to MORF-057 in the phase 1 trial
Phase 2a open-label trial design

12-week induction phase with rollover to 40-week maintenance phase in patients with moderate to severe ulcerative colitis scheduled to commence first quarter 2022
The primary endpoint is the change in Robarts Histopathological Index (RHI) at 12 weeks of treatment with MORF-057
Study will assess additional PK and PD measures including the key PD measure of α4β7 receptor occupancy
100 mg BID MORF-057 dose enrolling up to 30-35 patients
All phase 2 readiness work, including chronic toxicology studies, scheduled for completion in third and fourth quarters of 2021
Phase 2b randomized controlled trial design

Global, randomized, placebo-controlled trial enrolling approximately 280 patients with moderate to severe ulcerative colitis, staggered and in parallel to the phase 2a trial
The primary efficacy endpoint will be the proportion of subjects with Mayo Clinic Score Response at 12 weeks and patients will then be followed beyond the 52-weeks of treatment duration
The trial will also measure multiple secondary endpoints including Mayo Clinic Score Remission at 12 weeks, RHI, Patient Reported Outcome scores and translational markers
Multiple dose-ranging cohorts including at least one MORF-057 QD arm, at least one MORF-057 BID arm and one placebo arm
Presented positive preclinical data from Morphic’s immuno-oncology program demonstrating that small molecule inhibition of αvβ8, in combination with checkpoint inhibitors, potentiated anti-tumor activity in tumors refractory to checkpoint inhibition monotherapy
Appointed Susannah Gray, a veteran leader in healthcare finance and strategy with three decades of experience in capital formation, operational management, healthcare asset monetization, investment research and strategy implementations, to the Morphic Board of Directors and the Audit Committee of the Board of Directors
"The MORF-057 program has achieved the selectivity, PK, and PD trinity required for an oral α4β7 inhibitor. I’m extremely proud of the team who designed the molecule and the studies, and now excited to bring this program one step closer to the ultimate goal of helping patients with IBD," said Praveen Tipirneni, M.D., president and chief executive officer of Morphic Therapeutic. "Our vision had two parts. Deliver integrin therapeutics. At scale. With intense technical and business efforts, we’re well on our way to the first. The new MORF-057 clinical data, along with our robust fundraising activities, allow us to now imagine, build and scale our capabilities to advance additional programs including immuno-oncology with our αvβ8 inhibitors."

Financial Results for the Second Quarter 2021

Net loss for the quarter ended June 30, 2021 was $27.8 million or $0.77 per share compared to a net loss of $15.9 million or $0.52 per share for the same quarter last year
Revenue was $3.8 million for the quarter ended June 30, 2021 compared to $7.7 million for the same quarter last year
Research and development expenses were $24.6 million for the quarter ended June 30, 2021 as compared to $19.9 million for the same quarter last year. The increase was primarily due to costs associated with clinical trials costs associated with MORF 057 along with manufacturing costs associated with the upcoming phase 2 clinical trial
General and administrative expenses were $7.1 million for the quarter ended June 30, 2021, compared to $4.2 million for the same quarter last year. The increase was due to an increase in headcount and higher professional and consulting costs associated with Morphic operating as a public company
As of June 30, 2021, Morphic had cash, cash equivalents and marketable securities of $431.6 million, compared to $228.3 million as of December 31, 2020. Morphic believes its cash, cash equivalents and marketable securities as of June 30, 2021, will be sufficient to fund operating expenses and capital expenditure requirements until the end of 2024.

Biotech Company Looking to Detect HCC Early With Liquid Biopsy Based on Microbiome

On August 4, 2021 Micronoma, a San Diego company, reported its technology picks up signs of very early cancer from disrupted microbiome (Press release, Micronoma, AUG 4, 2021, View Source [SID1234585674]).

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Many researchers and companies are chasing the dream of detecting biomarkers of solid tumors in the blood, either to guide treatment, discover the cancer at an earlier, more treatable phase, or both. Liquid biopsies, as they are called, typically depend on finding a molecular signature of the cancer or some fragment of its DNA. Some liquid biopsy products are already approved and on the market.

Micronoma, a San Diego biotech company, is taking a different approach. The company is developing a technology designed to detect disruptions in the body’s microbiome — that vast array of bacteria and other organisms that inhabit the human body — caused by cancer. Micronomoa says its microbiome-based strategy will detect cancer at an earlier stage than other liquid biopsies.

The company announced recently that it is collaborating with researchers at the University of New South Wales in Australia on an effort to adapt its approach to early detection of liver. The collaboration is getting a boost from the Australian government in the form of a $4 million grant. Micronoma had previously focused on lung cancer, and its website talks about the advantages its technology has over low-dose CT scans for lung cancer screening.

Micronoma says its technology, which uses machine learning, can examine thousands of microbiome plasma features to discover, validate, and translate microbial-derived biomarkers for the early detection of hepatocellular carcinoma (HCC), the most common type of liver cancer, Micronoma said in a news release.

"The process is designed to improve the chances of survival of HCC patients and make effective risk disease stratification possible by discovering the disease in its earliest stages," Micronoma CEO Sandrine Miller-Montgomery told Managed Healthcare Executive.

HCC has a low overall 5-year survival rate (below 20%), primarily because themajority of patients are diagnosed at a late stage of the disease, Miller-Montgomery noted. "While HCC is still very deadly at stage 1 (the five-year survival rate is 34%) detection in stage 1 would still enable saving a significant number of lives," she said.

The cost savings to the overall healthcare system when the novel liquid biopsy detection method is implemented "will be huge, because early-stage treatment is significantly cheaper and more efficient than later stage treatment," Miller-Montgomery added.

The liquid biopsy diagnostic field is developing rapidly. Earlier this year, the FDA granted a Breakthrough Device designation for Bluestar Genomic’s proprietary noninvasive pancreatic cancer detection test in patients with new-onset diabetes.

Meanwhile, using a 400ul plasma sample, Micronoma’s initial preliminary test can detect next generation sequencing (NGS) microbial signatures that are a telltale sign of HCC, even in the earliest stages of the disease, Miller-Montgomery explained.

Micronoma’s method investigates signals from microbial signatures in the blood, which come from multiple sources, including the tumor itself and other locations, such as the GI tract.

After its research with UNSW is completed, it should take around two years for the technology to be commercially available. Micronoma is first prioritizing commercialization in the U.S. "but will work hard to expand our reach internationally, with Australia being top of the list.," Miller-Montgomery said

MannKind Corporation to Hold 2021 Second Quarter Financial Results Conference Call on August 11, 2021

On August 4, 2021 MannKind Corporation (Nasdaq:MNKD) reported that it will release its 2021 second quarter financial results and its management will host a conference call to discuss the financial results and corporate updates at 5:00 PM (Eastern Time) on Wednesday, August 11, 2021 (Press release, Mannkind, AUG 4, 2021, View Source [SID1234585673]).

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Presenting from the Company will be its Chief Executive Officer, Michael Castagna and Chief Financial Officer, Steven B. Binder.

Those interested in listening to the conference call live via the Internet may do so by visiting the Company’s website at View Source Events & Presentations. A replay will also be available on MannKind’s website for 14 days.

Clovis Oncology Announces Second Quarter 2021 Operating Results

On August 4, 2021 Clovis Oncology, Inc. (NASDAQ:CLVS) reported financial results for the quarter ended June 30, 2021, and provided an update on the Company’s clinical development programs and regulatory and commercial outlook for the rest of the year (Press release, Clovis Oncology, AUG 4, 2021, View Source [SID1234585672]).

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"While these are obviously complicated times, I’m encouraged that, based on the data available to us, we have maintained our US market share for Rubraca and achieved meaningful growth in Europe in the second-line maintenance ovarian cancer setting, and significantly advanced our development and pipeline programs during the quarter," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "Importantly, in the next six to 18 months, we expect three Phase 3 data read-outs for Rubraca, potentially expanding the number of ovarian and prostate cancer patients eligible for Rubraca treatment in the US and Europe, which we anticipate will drive growth in sales. In addition, we achieved a significant milestone in the second quarter with the initiation of our Phase 1/2 LuMIERE clinical study of FAP-2286, the first peptide-targeted radionuclide therapeutic targeting FAP in clinical development. This represents the first of multiple anticipated milestones in our strategy to develop innovative precision-targeted radiotherapies for a broad range of tumors."

Second Quarter 2021 Financial Results

Clovis reported global net product revenues for Rubraca of $36.8 million for Q2 2021, which included US product revenues of $27.7 million and ex-US product revenues of $9.1 million, respectively. This represents an 8% decrease year-over-year, compared to Q2 2020 net product revenues of $39.9 million, which included US net product revenues of $36.7 million and ex-US net product revenues of $3.2 million. The decrease was primarily due to fewer diagnoses and fewer patient starts, due to the ongoing COVID-19 pandemic.

Clovis reported net product revenue for Rubraca of $74.9 million for the six months ended June 30, 2021, which included US product revenue of $59.4 million and ex-U.S. product revenue of $15.5 million, compared to net product revenue for same period in 2020 of $82.5 million, which included US net product revenue of $76.0 million and ex-US net product revenue of $6.5 million.

Research and development expenses totaled $45.8 million for Q2 2021, down 35% compared to $69.9 million for the comparable period in 2020, due primarily to lower spending on Rubraca clinical trials. For the six months ended June 30, 2021, research and development expenses totaled $98.6 million, down 29% compared to $138.1 million for the comparable period in 2020. As previously discussed, the Company expects research and development expenses to be lower in the full year 2021 compared to 2020.

Selling, general and administrative expenses totaled $32.9 million for Q2 2021, down 21% compared to $41.9 million for the comparable period in 2020, due to overall cost reduction efforts. For the six months ended June 30, 2021, selling, general and administrative expenses totaled $62.9 million, down 26% compared to $84.5 million for the comparable period in 2020. Clovis continues to expect selling, general and administrative expenses to decrease in the full year 2021 compared to 2020.

Clovis reported a net loss for Q2 2021 of $66.4 million, or ($0.61) per share, compared to a net loss for Q2 2020 of $92.2 million, or ($1.15) per share. Net loss for Q2 2021 included share-based compensation expense of $7.4 million, compared to $13.3 million for the comparable period of 2020.

Clovis had $230.2 million in cash and cash equivalents as of June 30, 2021. During Q2 2021, the Company raised $72.5 million in net proceeds through its "at-the-market" equity offering program.

As of June 30, 2021, the Company had drawn $126.9 million under the Sixth Street Partners, LLC (SSP) ATHENA clinical trial financing and had up to $48.1 million available to draw under the agreement to fund the expenses of the ATHENA trial.

Net cash used in operating activities was $46.8 million for Q2 2021, down 22% from the $59.9 million reported in Q2 2020. Net cash used in operating activities for the first six months of 2021 was $108.6 million, down 24% from the same period in 2020.

Cash burn in Q2 2021 was $33.4 million, down 33% from $50.1 million in Q2 2020. Cash burn for the first six months of 2021 was $81.5 million, down 30% from $117.0 million in the first six months of 2020.

Clovis Oncology Pipeline Highlights

Three Anticipated Rubraca Phase 3 Read-outs in Next 6 to 18 Months

Top-line data from the ATHENA Phase 3 study in first-line maintenance treatment ovarian cancer setting evaluating Rubraca monotherapy versus placebo are now expected in the first quarter of 2022 based on event-based projections. Data from the combination arm of Rubraca plus Opdivo (nivolumab) versus Rubraca monotherapy are expected in the second half of 2022 based on protocol-defined assumptions.

Top-line data from the TRITON3 trial, which is expected to serve as the confirmatory study for Rubraca’s approval in metastatic castration-resistant prostate cancer (mCRPC) as well as a potential second-line label expansion, are expected in the second quarter of 2022. TRITON3 is a Phase 3 study evaluating Rubraca versus physician’s choice of chemotherapy or second-line androgen deprivation therapy in patients with mCRPC with BRCA and ATM mutations.

The three anticipated data readouts, ATHENA monotherapy, ATHENA combination and TRITON3, provide the potential to reach larger patient populations in earlier lines of therapy for ovarian and prostate cancers, in which Rubraca is currently approved in later-line indications. The timing for each data readout is contingent upon the occurrence of the protocol-specified progression-free survival (PFS) events.

LuMIERE Phase 1/2 Study of FAP-2286 Now Opened for Enrollment

FAP-2286 is Clovis Oncology’s peptide-targeted radionuclide therapy (PTRT) and imaging agent targeting fibroblast activation protein (FAP) and is the lead candidate in the Company’s TRT development program. Following FDA clearance of each of the treatment and imaging IND applications for FAP-2286, Clovis opened enrollment for the Phase 1/2 LuMIERE clinical study. The Phase 1 portion of the LuMIERE study will evaluate the safety of the FAP-targeting investigational therapeutic agent and identify the recommended Phase 2 dose and schedule of lutetium-177 labeled FAP-2286 (177Lu-FAP-2286). FAP-2286 labeled with gallium-68 (68Ga-FAP-2286) will be used as an investigational imaging agent to identify patients with FAP-positive tumors appropriate for treatment in LuMIERE. Once the Phase 2 dose is determined, Phase 2 expansion cohorts are planned in multiple tumor types.

Conference Call Details

Clovis will hold a conference call this morning, August 4, at 8:30 a.m. ET to discuss Q2 2021 results and provide an update on the Company’s clinical development programs and regulatory and commercial outlook for the rest of the year. The conference call will be simultaneously webcast on the Clovis Oncology website at clovisoncology.com, and archived for future review. Dial-in numbers for the conference call are as follows: US participants (877) 698-7048, International participants (647) 689-5448, conference ID: 3887398.

About Rubraca (rucaparib)

Rubraca is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3 being developed in multiple tumor types, including ovarian and prostate cancers, as monotherapy and in combination with other anti-cancer agents. Exploratory studies in other tumor types are also underway. Clovis holds worldwide rights for Rubraca.

In the United States, Rubraca is approved for the maintenance treatment of adult patients with recurrent epithelial, ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. Rubraca is also approved in the United States for the treatment of adult patients with deleterious BRCA mutation (germline and/or somatic) associated epithelial ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more chemotherapies and selected for therapy based on an FDA-approved companion diagnostic for Rubraca. Additionally, Rubraca is approved in the US for the treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor-directed therapy and a taxane-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for Rubraca. This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. The TRITON3 clinical trial is expected to serve as the confirmatory study for the Rubraca accelerated approval in mCRPC.

In Europe, Rubraca is approved for the maintenance treatment of adults with platinum-sensitive relapsed, high-grade epithelial, ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy. Rubraca is also approved in Europe for the treatment of adult patients with platinum sensitive, relapsed or progressive, BRCA mutated (germline and/or somatic), high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have been treated with two or more prior lines of platinum-based chemotherapy, and who are unable to tolerate further platinum-based chemotherapy.

Rubraca is an unlicensed medical product outside the US and Europe.

About FAP-2286

FAP-2286 is a clinical candidate under investigation as a peptide-targeted radionuclide therapy (PTRT) and imaging agent targeting fibroblast activation protein (FAP). FAP-2286 consists of two functional elements; a targeting peptide that binds to FAP and a site that can be used to attach radioactive isotopes for imaging and therapeutic use. FAP is highly expressed on cancer-associated fibroblasts (CAFs) in many epithelial cancers, including more than 90% of breast, lung, colorectal, and pancreatic carcinomas.i Clovis holds US and global rights for FAP-2286 excluding Europe, Russia, Turkey, and Israel.

FAP-2286 is an unlicensed medical product.

About Targeted Radionuclide Therapy

Targeted radionuclide therapy is an emerging class of cancer therapeutics, which seeks to deliver radiation directly to the tumor while minimizing delivery of radiation to normal tissue. Targeted radionuclides are created by linking radioactive isotopes, also known as radionuclides, to targeting molecules (e.g., peptides, antibodies, small molecules) that can bind specifically to tumor cells or other cells in the tumor environment. Based on the radioactive isotope selected, the resulting agent can be used to image and/or treat certain types of cancer. Agents that can be adapted for both therapeutic and imaging use are known as "theranostics." Clovis is developing a pipeline of novel, targeted radiotherapies for cancer treatment and imaging, including its lead candidate, FAP-2286, an investigational peptide-targeted radionuclide therapeutic (PTRT) and imaging agent, as well as three additional discovery-stage compounds.

Charles River Laboratories Announces Second-Quarter 2021 Results

On August 4, 2021 Charles River Laboratories International, Inc. (NYSE: CRL) reported its results for the second quarter of 2021 (Press release, Charles River Laboratories, AUG 4, 2021, View Source [SID1234585671]). For the quarter, revenue was $914.6 million, an increase of 34.0% from $682.6 million in the second quarter of 2020.

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Acquisitions contributed 6.0% to consolidated second-quarter revenue growth. The impact of foreign currency translation benefited reported revenue growth by 3.9%. Excluding the effect of these items, organic revenue growth was 24.1%, driven by contributions from all three business segments. The comparison to last year’s COVID-19-related impact increased the reported and organic revenue growth rates in the second quarter of 2021 by 8.6% and 8.0%, respectively, with the greatest impact in the Research Models and Services segment.

On a GAAP basis, second-quarter net income attributable to common shareholders was $88.4 million, an increase of 31.2% from net income of $67.4 million for the same period in 2020. Second-quarter diluted earnings per share on a GAAP basis were $1.72, an increase of 28.4% from $1.34 for the second quarter of 2020. The GAAP net income and earnings per share increases were primarily driven by higher revenue and operating margin improvement, partially offset by higher acquisition-related costs and a higher tax rate. In addition, the gain from the Company’s venture capital and other strategic investments totaled $0.14 per share in the second quarter of 2021, compared to a gain of $0.38 per share for the same period in 2020. The Company’s venture capital and other strategic investment performance has been excluded from non-GAAP results.

On a non-GAAP basis, net income was $133.8 million for the second quarter of 2021, an increase of 68.1% from $79.6 million for the same period in 2020. Second‑quarter diluted earnings per share on a non-GAAP basis were $2.61, an increase of 65.2% from $1.58 per share for the second quarter of 2020. The non-GAAP net income and earnings per share increases were primarily driven by higher revenue and operating margin improvement.

James C. Foster, Chairman, President and Chief Executive Officer, said, "The strength of our leading, non-clinical contract research and manufacturing portfolio was clearly demonstrated in our second-quarter financial performance. Robust industry fundamentals continue to drive unprecedented client demand across most of our businesses, and we are extremely well positioned to succeed in this environment."

"Due to the sustained demand, we are intensely focused on the execution of our strategy, including strengthening our portfolio and strategically adding staff and capacity to support our clients and provide exceptional service to them. We believe the success of this strategy will enable us to achieve our increased 2021 financial guidance, as well as our longer-term strategic and financial goals," Mr. Foster concluded.

Second-Quarter Segment Results

Research Models and Services (RMS)

Revenue for the RMS segment was $176.7 million in the second quarter of 2021, an increase of 51.6% from $116.5 million in the second quarter of 2020. The impact of foreign currency translation contributed 5.2%, and the acquisition of Cellero contributed 1.9% to second-quarter RMS revenue. Organic revenue growth of 44.5% was primarily driven by the year-over-year comparison to the COVID-19-related revenue impact in 2020, which contributed 35.0% on a reported basis and 33.4% on an organic basis to RMS revenue growth. Adjusted for the COVID-19 impact, RMS revenue growth was driven by robust demand for research models across all client segments and geographic regions, particularly in China, as well as higher revenue for research model services.

In the second quarter of 2021, the RMS segment’s GAAP operating margin increased to 24.1% from 3.3% in the second quarter of 2020, and on a non-GAAP basis, the operating margin increased to 27.4% from 9.1%. The GAAP and non-GAAP operating margin increases were driven primarily by operating leverage from higher sales volume of research models, due in part to the favorable comparison to last year’s COVID-19 impact.

Discovery and Safety Assessment (DSA)

Revenue for the DSA segment was $540.1 million in the second quarter of 2021, an increase of 22.0% from $442.6 million in the second quarter of 2020. The impact of foreign currency translation contributed 3.0%, and the acquisitions of Distributed Bio and Retrogenix contributed 0.9% to DSA revenue growth. Organic revenue growth of 18.1% was driven by strong demand in both the Discovery Services and Safety Assessment businesses from biotechnology and global biopharmaceutical clients, as well as a small benefit from the comparison to last year’s COVID-19 impact.

In the second quarter of 2021, the DSA segment’s GAAP operating margin increased to 19.4% from 16.3% in the second quarter of 2020, and on a non-GAAP basis, the operating margin increased to 23.5% from 23.2%. The GAAP and non-GAAP operating margin increases were driven primarily by operating leverage from higher revenue in both the Discovery Services and Safety Assessment businesses, partially offset by foreign currency translation. The impact of foreign currency translation reduced the DSA operating margin by approximately 150 basis points in the second quarter of 2021.

Manufacturing Solutions (Manufacturing)

Revenue for the Manufacturing segment was $197.8 million in the second quarter of 2021, an increase of 60.2% from $123.5 million in the second quarter of 2020. The impact of foreign currency translation contributed 5.4%, and the acquisition of Cognate BioServices (Cognate) contributed 28.2% to second-quarter Manufacturing revenue. Organic revenue growth of 26.6%, was driven primarily by robust demand in the Biologics Testing Solutions and Microbial Solutions businesses.

In the second quarter of 2021, the Manufacturing segment’s GAAP operating margin decreased to 28.7% from 34.8% in the second quarter of 2020, and on a non-GAAP basis, the operating margin decreased to 33.2% from 37.4%. The GAAP and non-GAAP operating margin decreases were driven primarily by the addition of Cognate, as well as higher production costs in the Microbial Solutions business. In addition, the GAAP operating margin declined due to higher amortization costs associated with Cognate.

Increases 2021 Guidance

The Company is increasing its 2021 financial guidance, which was previously provided on May 4, 2021, primarily as a result of the stronger-than-expected second-quarter financial performance and an expectation that robust client demand trends will continue for the remainder of the year.

The Company’s increased guidance for revenue growth, earnings per share, and free cash flow is as follows:

Footnotes to Guidance Table:

(1) The contribution from acquisitions reflects only those acquisitions that have been completed.
(2) Organic revenue growth is defined as reported revenue growth adjusted for acquisitions and foreign currency translation.
(3) Acquisition-related amortization includes an estimate of $0.05-$0.10 for the impact of the Vigene acquisition because the preliminary purchase price allocation has not been completed.
(4) These adjustments are related to the evaluation and integration of acquisitions, and primarily include transaction, advisory, and certain third-party integration costs, as well as certain costs associated with acquisition-related efficiency initiatives.
(5) These items primarily relate to charges of a) approximately $0.30 associated with U.S. and international tax legislation, and b) approximately $0.40 associated with debt extinguishment costs and the write-off of deferred financing costs related to debt refinancing.
(6) Venture capital and other strategic investment performance only includes recognized gains or losses. The Company does not forecast the future performance of these investments.
(7) Reconciliation of the current 2021 free cash flow guidance is as follows: Cash flow from operating activities of approximately $720 million, less capital expenditures of approximately $220 million, equates to free cash flow of approximately $500 million.

Webcast

Charles River has scheduled a live webcast on Wednesday, August 4, at 9:30 a.m. ET to discuss matters relating to this press release. To participate, please go to ir.criver.com and select the webcast link. You can also find the associated slide presentation and reconciliations of GAAP financial measures to non-GAAP financial measures on the website.

Non-GAAP Reconciliations

The Company reports non-GAAP results in this press release, which exclude often-one-time charges and other items that are outside of normal operations. A reconciliation of GAAP to non-GAAP results is provided in the schedules at the end of this press release.

Use of Non-GAAP Financial Measures

This press release contains non-GAAP financial measures, such as non-GAAP earnings per diluted share, which exclude the amortization of intangible assets, and other charges related to our acquisitions; expenses associated with evaluating and integrating acquisitions and divestitures, as well as fair value adjustments associated with contingent consideration; charges, gains, and losses attributable to businesses or properties we plan to close, consolidate, or divest; severance and other costs associated with our efficiency initiatives; the impact of the termination of the Company’s U.S. pension plan; the write-off of deferred financing costs and fees related to debt financing; third-party costs associated with the remediation of unauthorized access into our information systems detected in March 2019; investment gains or losses associated with our venture capital and other strategic equity investments; and adjustments related to the recognition of deferred tax assets expected to be utilized as a result of changes to the our international financing structure and the revaluation of deferred tax liabilities as a result of foreign tax legislation. This press release also refers to our revenue in both a GAAP and non-GAAP basis: "organic revenue growth," which we define as reported revenue growth adjusted for foreign currency translation, acquisitions, and divestitures. We exclude these items from the non-GAAP financial measures because they are outside our normal operations. There are limitations in using non-GAAP financial measures, as they are not presented in accordance with generally accepted accounting principles, and may be different than non-GAAP financial measures used by other companies. In particular, we believe that the inclusion of supplementary non-GAAP financial measures in this press release helps investors to gain a meaningful understanding of our core operating results and future prospects without the effect of these often-one-time charges, and is consistent with how management measures and forecasts the Company’s performance, especially when comparing such results to prior periods or forecasts. We believe that the financial impact of our acquisitions and divestitures (and in certain cases, the evaluation of such acquisitions and divestitures, whether or not ultimately consummated) is often large relative to our overall financial performance, which can adversely affect the comparability of our results on a period-to-period basis. In addition, certain activities and their underlying associated costs, such as business acquisitions, generally occur periodically but on an unpredictable basis. We calculate non-GAAP integration costs to include third-party integration costs incurred post-acquisition. Presenting revenue on an organic basis allows investors to measure our revenue growth exclusive of acquisitions, divestitures, and foreign currency exchange fluctuations more clearly. Non-GAAP results also allow investors to compare the Company’s operations against the financial results of other companies in the industry who similarly provide non-GAAP results. The non-GAAP financial measures included in this press release are not meant to be considered superior to or a substitute for results of operations presented in accordance with GAAP. The Company intends to continue to assess the potential value of reporting non-GAAP results consistent with applicable rules and regulations. Reconciliations of the non-GAAP financial measures used in this press release to the most directly comparable GAAP financial measures are set forth in this press release, and can also be found on the Company’s website at ir.criver.com.

Caution Concerning Forward-Looking Statements

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements may be identified by the use of words such as "anticipate," "believe," "expect," "intend," "will," "would," "may," "estimate," "plan," "outlook," and "project," and other similar expressions that predict or indicate future events or trends or that are not statements of historical matters. These statements also include statements regarding the impact of the COVID-19 pandemic; the projected future financial performance of Charles River and our specific businesses; the future demand for drug discovery and development products and services, including our expectations for future revenue trends; our expectations with respect to the impact of acquisitions completed in 2020 and 2021 on the Company, our service offerings, client perception, strategic relationships, revenue, revenue growth rates, and earnings; the development and performance of our services and products, including our investments in our portfolio; market and industry conditions including the outsourcing of services and spending trends by our clients; and Charles River’s future performance as delineated in our revised forward-looking guidance, and particularly our expectations with respect to revenue, the impact of foreign exchange, enhanced efficiency initiatives, and the assumptions surrounding the COVID-19 pandemic that form the basis for our revised annual guidance. Forward-looking statements are based on Charles River’s current expectations and beliefs, and involve a number of risks and uncertainties that are difficult to predict and that could cause actual results to differ materially from those stated or implied by the forward-looking statements. Those risks and uncertainties include, but are not limited to: the COVID-19 pandemic, its duration, its impact on our business, results of operations, financial condition, liquidity, business practices, operations, suppliers, third party service providers, clients, employees, industry, ability to meet future performance obligations, ability to efficiently implement advisable safety precautions, and internal controls over financial reporting; the COVID-19 pandemic’s impact on client demand, the global economy and financial markets; the ability to successfully integrate businesses we acquire (including Cognate BioServices and Vigene Biosciences, and risks and uncertainties associated with Cognate’s and Vigene’s products and services, which are in areas that the Company did not previously operate); the timing and magnitude of our share repurchases; negative trends in research and development spending, negative trends in the level of outsourced services, or other cost reduction actions by our clients; the ability to convert backlog to revenue; special interest groups; contaminations; industry trends; new displacement technologies; USDA and FDA regulations; changes in law; the impact of Brexit; continued availability of products and supplies; loss of key personnel; interest rate and foreign currency exchange rate fluctuations; changes in tax regulation and laws; changes in generally accepted accounting principles; and any changes in business, political, or economic conditions due to the threat of future terrorist activity in the U.S. and other parts of the world, and related U.S. military action overseas. A further description of these risks, uncertainties, and other matters can be found in the Risk Factors detailed in Charles River’s Annual Report on Form 10-K as filed on February 17, 2021 and the Quarterly Report on Form 10-Q as filed on May 4, 2021, as well as other filings we make with the Securities and Exchange Commission. Because forward-looking statements involve risks and uncertainties, actual results and events may differ materially from results and events currently expected by Charles River, and Charles River assumes no obligation and expressly disclaims any duty to update information contained in this press release except as required by law.

Assessment of COVID-19 Impact in 2020

In this press release, the Company has provided its assessment for the impact from the COVID-19 pandemic in 2020, including on the Company’s revenue. This assessment was determined using methodologies, assumptions, and estimates that vary depending on the specific reporting segment and situation. For the Research Models and Services segment, the assessment was primarily based on comparisons to daily historical research model sales volumes prior to the COVID-19 pandemic and the subsequent reduction in research model order activity associated with our clients’ COVID-19 pandemic-related site closures and/or their reduced on-site activity, as well as our discussions with clients, particularly of our research model services and HemaCare businesses, with regard to revenue expectations and operational impacts from the COVID-19 pandemic. For the Discovery and Safety Assessment segment, the assessment was based on multiple factors including, but not limited to, discussions with clients with regard to the cause of delays to discovery projects and safety assessment studies, location-specific actions to ensure employee safety in our facilities, the impact of remote versus in-person activities and services, and supply chain delays and other resource constraints. For the Manufacturing Solutions segment, the assessment was based on multiple factors including, but not limited to, analysis of the sales impact due to the COVID-19 pandemic, assessments of idle instruments and the related revenue streams due to the inability to access clients’ sites, as well as discussions with clients with regard to their revenue expectations and operations. The estimated revenue loss related to COVID-19 was also expected to be partially offset by incremental work on clients’ COVID-19 programs. Because this assessment involves risks and uncertainties, actual events and results may differ materially from these estimates and assumptions, and Charles River assumes no obligation and expressly disclaims any duty to update them.