On May 4, 2022 Clovis Oncology, Inc. (NASDAQ:CLVS) reported financial results for the quarter ended March 31, 2022, and provided an update on the Company’s clinical development programs and regulatory and commercial outlook (Press release, Clovis Oncology, MAY 4, 2022, View Source [SID1234613479]).

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"We entered 2022 knowing that it would be the most significant year for clinical data read-outs in the Company’s history, and we are obviously pleased that the results from the ATHENA-MONO study of Rubraca, the first of those read-outs, exceeded our expectations. Importantly, we believe that the positive results from ATHENA-MONO, which will be described in full at ASCO (Free ASCO Whitepaper) next month, demonstrate the benefit that Rubraca can provide as an important new treatment option for women with advanced ovarian cancer in the first-line maintenance setting," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "We continue to anticipate two additional Phase 3 read-outs for Rubraca: TRITON3 in second-line prostate cancer treatment for selected patients during the third quarter this year, and ATHENA-COMBO in combination with Opdivo in first-line ovarian cancer maintenance treatment in the first quarter of 2023. Importantly, for our first targeted radiotherapy candidate, FAP-2286, we look forward to presenting initial data from the Phase 1 portion of the LuMIERE study at the SNMMI Annual Meeting next month, and initiating the Phase 2 portion of the study during the fourth quarter."

First Quarter 2022 Financial Results

Clovis reported global net product revenues for Rubraca of $34.2 million for Q1 2022, which included US product revenues of $24.5 million and ex-US product revenues of $9.7 million. This represents a 5% decrease over Q4 2021 and a 10% decrease year-over-year, compared to Q1 2021 net product revenues of $38.1 million, which included US net product revenues of $31.7 million and ex-US net product revenues of $6.4 million. The decrease was primarily due to fewer diagnoses and fewer patient starts in the US.

Research and development expenses totaled $42.3 million for Q1 2022, down 20% compared to $52.8 million for the comparable period in 2021, due primarily to lower spending on Rubraca clinical trials. Clovis expects research and development expenses in the full year 2022 to be comparable to 2021.

Selling, general and administrative expenses totaled $29.2 million for Q1 2022, down 2% compared to $29.9 million for the comparable period in 2021. Clovis expects selling, general and administrative expenses in the full year 2022 to be comparable to 2021.

Clovis reported a net loss for Q1 2022 of $60.2 million, or ($0.44) per share, compared to a net loss for Q1 2021 of $66.3 million, or ($0.64) per share. Net loss for Q1 2022 included share-based compensation expense of $6.6 million, compared to $4.0 million for the comparable period of 2021.

Clovis had $122.2 million in cash and cash equivalents as of March 31, 2022. During Q1 2022, the Company raised $28.6 million in net proceeds through its "at-the-market" equity offering program. Clovis remains focused on its liquidity position and is committed to raising additional capital in the near term in order to fund its operating plan for the next 12 months and beyond.

As of March 31, 2022, the Company had drawn $156.4 million under the Sixth Street Partners, LLC (SSP) ATHENA clinical trial financing and had up to $18.6 million available to draw under the agreement to fund the expenses of the ATHENA trial.

Net cash used in operating activities was $58.5 million for Q1 2022, down 5% from the $61.9 million reported in Q1 2021. Cash burn in Q1 2022 was $49.3 million, up 2% from $48.1 million in Q1 2021. As costs for the ATHENA trial are reducing, SSP funding was $4.6 million lower in Q1 2022 vs Q1 2021.

Clovis Oncology Pipeline Highlights

ATHENA-MONO Successfully Achieved Primary PFS Endpoint; Data to be Presented at ASCO (Free ASCO Whitepaper) 2022

The monotherapy portion of the ATHENA (GOG 3020/ENGOT-ov45) trial (ATHENA-MONO) enrolled 538 women with high-grade ovarian, fallopian tube, or primary peritoneal cancer. The primary efficacy analysis evaluated two prospectively defined molecular sub-groups in a step-down manner: 1) HRD-positive (inclusive of BRCAm tumors), and 2) all patients randomized (intent-to-treat, or ITT) in ATHENA-MONO.

Positive top-line data from the monotherapy portion of ATHENA-MONO demonstrated Rubraca as maintenance treatment successfully achieved the primary endpoint of significantly improved investigator-assessed progression-free survival (PFS) compared with placebo.

Benefit was observed in both primary efficacy analyses of newly-diagnosed patients with advanced ovarian cancer following successful treatment with platinum-based chemotherapy.

The rucaparib arm successfully achieved statistical significance over the placebo arm for the primary endpoint of PFS in the homologous recombination deficiency (HRD-positive) patient population with a hazard ratio of 0.47 (95% CI: 0.31-0.72). The median PFS for these patients treated with rucaparib was 28.7 months vs 11.3 months among those who received placebo (p=0.0004).
Rucaparib also showed statistical significance over the placebo arm for PFS for all 538 patients enrolled in the ATHENA-MONO comparison with a hazard ratio of 0.52 (95% CI: 0.40-0.68). The median PFS for all patients enrolled in ATHENA-MONO and treated with rucaparib was 20.2 months vs 9.2 months among those who received placebo (p<0.0001).
Benefit in PFS was also seen in the exploratory subgroups of patients with BRCA mutant (BRCAm) tumors, those with BRCA wild type, HRD-positive and HRD-negative tumors, and those whose biomarker status could not be determined.

The PFS endpoint in the exploratory subgroup of BRCAm demonstrated a hazard ratio of 0.40 (95% CI: 0.21-0.75). The median PFS for these patients treated with rucaparib was Not Reached vs 14.7 months for those who received placebo.
The PFS endpoint in the exploratory subgroup of BRCA wild type HRD-negative demonstrated a hazard ratio of 0.65 (95% CI: 0.45-0.95). The median PFS for these patients treated with rucaparib was 12.1 months vs. 9.1 months for those who received placebo.
The PFS endpoint in the exploratory subgroup of BRCA wild type HRD-positive demonstrated a hazard ratio of 0.58 (95% CI: 0.33-1.01). The median PFS for these patients treated with rucaparib was 20.3 months vs. 9.2 months for those who received placebo.
The PFS endpoint in the exploratory subgroup of patients whose biomarker status could not be determined demonstrated a hazard ratio of 0.39 (95% CI: 0.20-0.78). The median PFS for these patients treated with rucaparib was 17.5 months vs. 8.9 months for those who received placebo.
The safety of Rubraca observed in ATHENA-MONO was consistent with both the current US and European labels. The most common (≥5%) treatment-emergent grade 3/4 adverse events (TEAEs) among all patients treated with rucaparib in the monotherapy portion of the ATHENA study were anemia/decreased hemoglobin (28.7%), neutropenia (14.6%), ALT/AST increase (10.6%), and thrombocytopenia (7.1%). The discontinuation rate for TEAEs was 11.8% for rucaparib-treated patients and 5.5% for the placebo arm. The rate of treatment-emergent myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) in the rucaparib arm was 0.2%, and no patients on the placebo arm experienced treatment-emergent MDS/AML.

We presently intend to submit a supplemental New Drug Application (sNDA) to the FDA and, subject to EMA discussions, a Type II variation to the EMA for a first-line maintenance treatment indication for women with advanced ovarian cancer who have responded to first-line platinum-based chemotherapy. We are engaged in discussions with FDA on the scope and timing of the submission, and we expect that the regulatory agencies will review the overall results as well as results by individual subgroups in making their assessment.

The ATHENA-MONO data have been accepted as a late-breaker abstract and will be presented in an oral session at the 2022 ASCO (Free ASCO Whitepaper) Annual Meeting on June 6 in Chicago. Clovis Oncology plans to provide an expanded description of the ATHENA-MONO study results, including Kaplan-Meier curves and key secondary endpoints including PFS results by blinded independent centralized review (BICR) and other analyses.

Two Remaining Rubraca Phase 3 Study Readouts Expected in Next 12 Months

Top-line data from the ATHENA-COMBO portion of the ATHENA Phase 3 study in first-line maintenance treatment ovarian cancer setting evaluating Rubraca plus Opdivo (nivolumab) versus Rubraca monotherapy are expected in the first quarter of 2023.

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 now expected in the third quarter of 2022 instead of the second quarter of 2022 based on a slower than expected event count. 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 or ATM mutations with a primary endpoint of radiologic PFS.

The timing for each Phase 3 data readout is contingent upon the occurrence of the protocol-specified PFS events, and timing estimates are based on event-based projections.

LuMIERE Phase 1/2 Study of FAP-2286 Enrolling Patients with FAP-Positive Solid Tumors into Phase 1; Initial Phase 1 LuMIERE Data to be Presented in an Oral Session at SNMMI 2022 Annual Meeting

FAP-2286 is the first peptide-targeted radionuclide therapy (PTRT) and imaging agent targeting fibroblast activation protein (FAP) to enter clinical development and is the lead candidate in Clovis Oncology’s targeted radiotherapy (TRT) development program. The Phase 1 portion of the LuMIERE study, for which enrollment in the third dose cohort has begun, is evaluating the safety of the FAP-targeting investigational therapeutic agent and will 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) is being used as an investigational imaging agent to identify patients with FAP-positive tumors appropriate for treatment in LuMIERE. Initial Phase 1 data from LuMIERE will be presented in an oral session at the SNMMI 2022 Annual Meeting on June 14 in Vancouver, British Columbia. Once the Phase 2 dose is determined, Phase 2 expansion cohorts are planned in multiple tumor types and are expected to initiate in the fourth quarter of 2022.

Beyond Clovis’ commitment to developing 177Lu-FAP-2286, the Company is also exploring an alpha-particle emitting compound, and in March, Clovis initiated a development, manufacturing, and services agreement with Evergreen Theragnostics to develop actinium-225-labeled-FAP-2286 (225Ac-FAP-2286). Under the agreement, Clovis and Evergreen intend to develop radiolabeling chemistry and analytical methods for use in potential future pre-clinical and clinical studies.

For more information about FAP-2286, TRT, or Clovis’ TRT development program, click here.

Conference Call Details

Clovis will hold a conference call this morning, May 4, at 8:30 am ET, to discuss Q1 2022 results and provide an update on the Company’s clinical development programs and regulatory and commercial outlook. 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 888.440.4615, International participants 646.960.0682, conference ID: 2259685.

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. High FAP expression has been shown in pancreatic ductal adenocarcinoma, salivary gland, mesothelioma, colon, bladder, sarcoma, squamous non-small cell lung, squamous head and neck cancers, and cancers of unknown primary. High FAP expression was detected in both primary and metastatic tumor samples and was independent of tumor stage or grade. 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.

On May 4, 2022 Charles River Laboratories International, Inc. (NYSE: CRL) reported its results for the first quarter of 2022 (Press release, Charles River Laboratories, MAY 4, 2022, View Source [SID1234613478]). For the quarter, revenue was $913.9 million, an increase of 10.8% from $824.6 million in the first quarter of 2021.

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Acquisitions contributed 4.7% to consolidated first-quarter revenue growth. The divestiture of the Research Models and Services operations in Japan (RMS Japan) in October 2021 reduced reported revenue growth by 1.6%. The impact of foreign currency translation reduced reported revenue growth by 1.7%. Excluding the effect of these items, organic revenue growth of 9.4% was driven by contributions from all three business segments.

On a GAAP basis, first-quarter net income attributable to common shareholders was $93.0 million, an increase of 51.2% from net income of $61.5 million for the same period in 2021. First-quarter diluted earnings per share on a GAAP basis were $1.81, an increase of 50.8% from $1.20 for the first quarter of 2021. The increases in the GAAP net income and earnings per share were driven primarily by higher revenue and operating income, as well as lower costs associated with the Company’s debt refinancing activities in the first quarter of 2021.

On a non-GAAP basis, net income from continuing operations was $141.1 million for the first quarter of 2022, an increase of 9.3% from $129.2 million for the same period in 2021. First‑quarter diluted earnings per share on a non-GAAP basis were $2.75, an increase of 8.7% from $2.53 per share for the first quarter of 2021. The non-GAAP net income and earnings per share increases were driven primarily by higher revenue and operating margin improvement, partially offset by a higher tax rate and increased interest expense.

James C. Foster, Chairman, President and Chief Executive Officer, said, "We are pleased with our solid, first-quarter financial results that were in line with our expectations, and believe we are continuing to distinguish ourselves from the competition in the current business environment. We continue to benefit from strong, sustained business trends, including record booking activity and robust backlog growth in the Discovery and Safety Assessment segment, that is affording us exceptional visibility into future demand as studies are booked well into 2023. We believe these trends, coupled with the continued strength of biopharmaceutical client spending, support our expectation that the revenue growth rate will accelerate from the first-quarter level, positioning us to achieve our financial guidance for the year."

First-Quarter Segment Results

Research Models and Services (RMS)

Revenue for the RMS segment was $176.5 million in the first quarter of 2022, essentially unchanged from $176.9 million in the first quarter of 2021. Reported revenue growth was reduced by 7.7% due to the divestiture of RMS Japan, and by 1.2% due to the impact of foreign currency translation. Organic revenue growth of 8.7% was driven by broad-based growth for research models, particularly in North America, and research model services, particularly in the Insourcing Solutions (IS) business.

In the first quarter of 2022, the RMS segment’s GAAP operating margin increased to 27.1% from 25.4% in the first quarter of 2021. On a non-GAAP basis, the operating margin increased to 29.9% from 28.7% in the first quarter of 2021. The GAAP and non-GAAP operating margin increases were driven primarily by operating leverage from higher sales of research models.

Discovery and Safety Assessment (DSA)

Revenue for the DSA segment was $544.3 million in the first quarter of 2022, an increase of 8.6% from $501.2 million in the first quarter of 2021. The impact of foreign currency translation reduced revenue by 1.6%, while acquisitions contributed 0.7% to DSA revenue growth. Organic revenue growth of 9.5% was primarily driven by the Safety Assessment business.

In the first quarter of 2022, the DSA segment’s GAAP operating margin increased to 19.3% from 18.1% in the first quarter of 2021. The GAAP operating margin increase was driven by lower acquisition-related adjustments associated with contingent consideration. On a non-GAAP basis, the operating margin decreased to 22.9% from 23.8% in the first quarter of 2021, primarily reflecting higher staffing costs.

Manufacturing Solutions (Manufacturing)

Revenue for the Manufacturing segment was $193.1 million in the first quarter of 2022, an increase of 31.8% from $146.5 million in the first quarter of 2021. The acquisitions of the Cognate BioServices (Cognate) and Vigene Biosciences (Vigene) CDMO businesses contributed 24.4% to Manufacturing revenue growth, while the impact of foreign currency translation reduced revenue by 2.7%. Organic revenue growth of 10.1% was driven by strong demand for Biologics Testing Solutions services, with Microbial Solutions revenue also increasing.

In the first quarter of 2022, the Manufacturing segment’s GAAP operating margin decreased to 24.0% from 33.8% in the first quarter of 2021. On a non-GAAP basis, the operating margin decreased to 33.1% from 35.5% in the first quarter of 2021. The GAAP and non-GAAP operating margin decreases were driven primarily by the additions of Cognate and Vigene. Higher amortization and other integration costs associated with these acquisitions also contributed to the GAAP operating margin decline.

Updates 2022 Guidance

The Company is updating its 2022 financial guidance, which was previously provided on February 16, 2022. Reported revenue growth guidance is being increased by 50 basis points to 13.5% to 15.5% to reflect the Explora BioLabs acquisition, which was completed on April 5, 2022, partially offset by unfavorable movements in foreign currency translation. Organic revenue growth guidance remains unchanged for 2022.

The Company is maintaining its non-GAAP earnings per share guidance as a result of its first-quarter financial performance that was in line with prior expectations and an outlook of accelerating revenue growth during the remainder of the year. The 2022 non-GAAP earnings per share outlook includes a higher-than-expected tax rate, due principally to a lower excess tax benefit associated with stock-based compensation in the first quarter, as well as increased interest expense due to higher rate assumptions for the year. GAAP earnings per share guidance is being lowered to reflect amortization and other acquisition-related costs associated with Explora BioLabs, as well as the first-quarter loss from venture capital and other strategic investments.

Footnotes to Guidance Table:

(1) The contribution from acquisitions/divestitures (net) reflects only those transactions that have been completed.

(2) Organic revenue growth is defined as reported revenue growth adjusted for acquisitions, divestitures, the 53rd week in 2022, and foreign currency translation.

(3) Acquisition-related amortization includes an estimate of $0.05-$0.15 for the impact of the Explora BioLabs acquisition because the preliminary purchase price allocation has not been completed.

(4) These adjustments are related to the evaluation and integration of acquisitions and divestitures, and primarily include transaction, advisory, and certain third-party integration costs, as well as adjustments related to contingent consideration and certain costs associated with acquisition-related efficiency initiatives.

(5) Venture capital and other strategic investment performance only includes recognized gains or losses. The Company does not forecast the future performance of these investments.

(6) These items primarily relate to charges associated with U.S. and international tax legislation that necessitated changes to the Company’s international financing structure; environmental litigation costs related to the Microbial Solutions business; and severance and other costs related to the Company’s efficiency initiatives.

Webcast

Charles River has scheduled a live webcast on Wednesday, May 4th, 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.

Bank of America Healthcare Conference Presentation

Charles River will present at the Bank of America 2022 Healthcare Conference in Las Vegas, Nevada, on Wednesday, May 11th, at 1:20 p.m. PT (4:20pm ET). Management will provide an overview of Charles River’s strategic focus and business developments.

A live webcast of the presentation will be available through a link that will be posted on ir.criver.com. A webcast replay will be accessible through the same website shortly after the presentation and will remain available for approximately two weeks.

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.

On May 4, 2022 Neurocrine Biosciences, Inc. (Nasdaq: NBIX) reported its financial results for the first quarter ended March 31, 2022 and reiterated financial guidance for 2022 (Press release, Neurocrine Biosciences, MAY 4, 2022, View Source [SID1234613477]).

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"INGREZZA’s first quarter performance reflects the opportunity we have to help patients living with tardive dyskinesia (TD). We completed our salesforce expansion in April and we now have three dedicated teams across psychiatry, neurology, and long-term care who are focused on improving diagnosis and treatment rates for TD," said Kevin Gorman, Ph.D., Chief Executive Officer of Neurocrine Biosciences. "With a growing product in INGREZZA, several mid-to-late-stage clinical data read-outs this year and next, and a strong financial profile, Neurocrine Biosciences continues to establish our position as a leading neuroscience-focused company."

Financial Highlights

First Quarter INGREZZA Net Product Sales and Commercial Highlights:

Net product sales were $303 million with total prescriptions (TRx) of approximately 57,600
Net product sales and TRx grew 32% and 33%, respectively, vs. first quarter of 2021
Improved levels of persistence and compliance for existing patients when compared to prior first quarters driven by strong commercial execution
Record number of new patients
In April 2022, salesforce expansion was completed establishing separate psychiatry, neurology, and long-term care teams
Financial Highlights:

First quarter 2022 GAAP net income and diluted earnings per share of $14 million and $0.14, respectively, compared with $32 million and $0.33, respectively, for first quarter 2021
First quarter 2022 non-GAAP net income and diluted earnings per share of $30 million and $0.30, respectively, compared with $49 million and $0.50, respectively, for first quarter 2021
Differences in first quarter 2022 GAAP and non-GAAP financial results compared with first quarter 2021 driven by:
Increased R&D expense in support of an expanded and advancing clinical portfolio
Increased SG&A expense primarily due to ongoing commercial initiatives, including the TD Spotlight-branded direct-to-consumer INGREZZA advertising campaign which launched in May 2021 and deployment of the expanded salesforce in March 2022
At March 31, 2022, the Company had cash, cash equivalents and marketable securities of $1.2 billion
A reconciliation of GAAP to non-GAAP financial results can be found in Table 3 and Table 4 at the end of this earnings release.

Recent Events:

In March 2022, Mitsubishi Tanabe Pharma Corporation (MTPC) received Japanese Ministry of Health, Labour and Welfare approval for DYSVAL (valbenazine) for the treatment of tardive dyskinesia in Japan. Under the terms of the license agreement, the Company is entitled to receive a milestone payment of $20 million upon MTPC’s first commercial sale of DYSVAL in Japan, which is expected to occur in the second quarter of 2022.
In April 2022, Neurocrine Biosciences presented Phase 3 data for the KINECT-HD study evaluating valbenazine for chorea associated with Huntington disease. In the study, valbenazine met the primary endpoint of significant (p<0.0001) improvement in chorea severity versus placebo as measured by the Unified Huntington’s Disease Rating Scale (UHDRS) Total Maximal Chorea (TMC) Score, with improvements beginning in week 2. Clinically meaningful results, demonstrated by greater response rates, were seen by clinicians (CGI-C) and patients (PGI-C) for valbenazine versus placebo. In addition, the safety profile was consistent with the known safety profile of valbenazine. The Company plans to submit a supplemental New Drug Application to the U.S. Food and Drug Administration in the second half of 2022.
Reiterated 2022 INGREZZA Sales and Operating Expense Guidance:

INGREZZA sales guidance for fiscal 2022 reflects approximately 20% year-over-year growth, at the mid-point of the range, and is based on recent trends, an anticipated improving COVID-19 related environment throughout the year, and benefit from our recently completed salesforce expansion during the second half of 2022. If new COVID-19 related disruptions emerge, the Company’s ability to meet these expectations could be negatively impacted.
GAAP R&D guidance includes amounts for milestones that are probable of achievement or have been achieved and (ii) amounts for in-process research and development once significant collaboration and licensing arrangements have been completed. GAAP R&D Guidance includes approximately $7 million of milestone expense for the Xenon collaboration which was achieved in January 2022.
Non-GAAP guidance adjusted to exclude estimated non-cash stock-based compensation expense of $60 million in R&D and $110 million in SG&A.
Based upon Federal NOL’s and tax credits, the Company expects to begin making cash payments for Federal income tax beginning in the fourth quarter of 2022.

Expected Future Milestones and Key Activities

Key: VMAT2 = Vesicular Monoamine Transporter 2; CaV = Calcium Channel, Voltage-Gated; CSWS = Epileptic Encephalopathy with Continuous Spike and Wave During Sleep; M4= M4 Muscarinic Receptor; CFR1 = Corticotropin-Releasing Factor Type 1; AMPA = Alpha-Amino-3-Hydroxy-5-Methyl-4-Isoxazole Propionic Acid; GPR = Orphan G Protein Coupled Receptor; NaV1.6 = Sodium Channel, Voltage-Gated

Neurocrine Bioscience Partners: * Mitsubishi Tanabe Pharma Corporation has commercialization rights in East Asia;
** In-Licensed from Idorsia Pharmaceuticals; † In-Licensed from Sosei Group Corporation; ‡ Partnered with Takeda Pharmaceutical Company Limited; ∝ In-Licensed from Xenon Pharmaceuticals

Conference Call and Webcast Today at 8:00 AM Eastern Time
Neurocrine Biosciences will hold a live conference call and webcast today at 8:00 a.m. Eastern Time (5:00 a.m. Pacific Time). Participants can access the live conference call by dialing 800-895-3361 (US) or 785-424-1062 (International) using the conference ID: NBIX. The webcast can also be accessed on Neurocrine Biosciences’ website under Investors at www.neurocrine.com. A replay of the webcast will be available on the website approximately one hour after the conclusion of the event and will be archived for approximately one month.

On May 4, 2022 Oncorus, Inc. (Nasdaq: ONCR), a viral immunotherapies company focused on driving innovation to transform outcomes for cancer patients, reported first quarter 2022 financial results and highlighted recent achievements and developments (Press release, Oncorus, MAY 4, 2022, View Source [SID1234613476]).

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"Early 2022 has been focused on clinical and operational execution as we work toward operational completion of our manufacturing facility, as well as extending our cash runway to support our dual platform approach to next-generation viral immunotherapies. We plan to share additional ONCR-177 Phase 1 data from the surface lesion monotherapy expansion and the initial combination expansion data with KEYTRUDA in the second half of 2022, while we continue to advance our vRNA drug candidates and LNP capabilities in parallel," said Theodore (Ted) Ashburn, M.D., Ph.D., President and Chief Executive Officer of Oncorus. "We recently presented exciting preclinical data from our selectively self-amplifying vRNA/LNP immunotherapy platform at AACR (Free AACR Whitepaper) demonstrating the full potential of our IV-administered viral immunotherapy candidates, ONCR-021 and ONCR-788, in overcoming well-established limitations of RNA-based therapeutics. We look forward to further positioning Oncorus for growth driven by our dual-platform pipeline of product candidates targeting cancers with significant unmet need, which is enabled by our wholly owned GMP-compliant manufacturing infrastructure."

First Quarter 2022 and Recent Business Highlights

On track to report additional ONCR-177 monotherapy and combination data in the second half of 2022. Oncorus has completed enrollment in the dose expansion portion of its Phase 1 open-label, multi-center trial in patients with advanced and/or refractory cutaneous, subcutaneous or metastatic nodal solid tumors or with liver metastases of solid tumors. The Company continues to enroll patients in the combination cohort with future data readouts expected in the second half of 2022. Data readouts are expected to include both additional surface lesion monotherapy expansion data for ONCR-177 and initial surface lesion combination expansion data for ONCR-177 administered with KEYTRUDA.
Presented preclinical data for ONCR-021 and ONCR-788 supporting the company’s selectively self-amplifying viral RNA (vRNA)/lipid nanoparticle (LNP) immunotherapy platform at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022. In April 2022, Oncorus presented preclinical data for both ONCR-021 and ONCR-788 in two e-posters at the AACR (Free AACR Whitepaper) Annual Meeting demonstrating robust preclinical anti-tumor efficacy in multiple tumor models while avoiding the challenges seen in previous studies that incorporate IV administration of RNA-based oncology therapeutics. Oncorus plans to submit an investigational new drug (IND) application for ONCR-021 with the U.S. Food and Drug Administration (FDA) in mid-2023 and a subsequent IND submission for ONCR-788.
Announced debt capital facility with K2 HealthVentures (K2HV); $20 million funded at closing: In April 2022, Oncorus entered into a loan and security agreement with K2HV, a healthcare-focused specialty finance company. The term loan facility provides Oncorus with up to $45 million available in multiple tranches upon the achievement of certain time-based, clinical and regulatory milestones, with the initial tranche of $20 million funded at closing. Oncorus intends to use the proceeds of the initial tranche of the loan facility to complete the buildout of its Andover facility and to continue the advancement of its pipeline of next generation viral immunotherapies for cancer and LNP technologies.
Announced relocation of all operations to Andover, Massachusetts facility in fourth quarter of 2022 to increase operational efficiency: In April 2022, Oncorus announced plans to relocate all operations to its facility in Andover, Massachusetts in the fourth quarter of 2022, allowing research, process development and Good Manufacturing Practice (GMP)-compliant manufacturing to occur all in one facility.
First Quarter 2022 Financial Results

Cash and cash equivalents and investments totaled $98.7 million as of March 31, 2022 compared to $123.9 million as of December 31, 2021.

Research and development expenses for the quarter ended March 31, 2022 were $12.5 million compared to $8.4 million for the corresponding quarter in 2021. The increase was primarily attributable to employee compensation costs, which was driven by increased headcount and increased stock-based compensation, increased development costs related to the Company’s nominated candidates, as well as increased rent expense related to the Company’s manufacturing facility.

General and administrative expenses for the quarter ended March 31, 2022 were $5.3 million compared to $4.2 million for the corresponding quarter in 2021. The increase was primarily attributable to employee compensation costs, including higher stock-based compensation, increased headcount and increased salary and related expenses.

Net loss for the quarter ended March 31, 2022 was $17.8 million, or $0.69 per share, as compared to a net loss of $12.7 million, or $0.53 per share for the corresponding quarter in 2021. The increase in net loss was due to increased expenses associated with the Company’s preclinical development costs of its nominated candidates.
Financial Guidance

As a result of the debt capital facility and operations relocation, as well as other initiatives to increase operational efficiency, Oncorus now expects its cash, cash equivalents and investments to fund its capital expenditures and operating expenses into early 2024.

On May 4, 2022 Horizon Therapeutics plc (Nasdaq: HZNP) reported first-quarter 2022 financial results and maintained its full-year 2022 net sales and adjusted EBITDA guidance (Press release, Horizon Pharma, MAY 4, 2022, View Source [SID1234613475]).

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"Our first quarter financial and operational performance established a strong start to the year, with meaningful progress on our strategic priorities and positioning us well for another year of top-tier growth," said Tim Walbert, chairman, president and chief executive officer, Horizon. "We advanced our pipeline with the initiation of two clinical trials, drove strong performance of our key growth drivers, TEPEZZA, KRYSTEXXA and UPLIZNA, and continued our international expansion. In addition, the FDA granted priority review of our sBLA to expand the KRYSTEXXA label to include co-treatment of KRYSTEXXA plus methotrexate, marking an important milestone in our journey to help more uncontrolled gout patients benefit from the medicine."

First-quarter 2021 results were negatively impacted by a short-term TEPEZZA supply disruption due to U.S. government-mandated COVID 19-vaccine orders.

First Quarter and Recent Company Highlights

FDA Granted Priority Review of sBLA for Co-Treatment of KRYSTEXXA Plus Methotrexate: In March, the U.S. Food and Drug Administration (FDA) granted priority review of the Company’s sBLA to expand the label for KRYSTEXXA to include co-treatment with methotrexate. The Company submitted an sBLA in January based on results from the MIRROR Phase 4 randomized placebo-controlled trial which demonstrated that 71% of patients receiving KRYSTEXXA plus methotrexate achieved a complete response, a more than 30 percentage-point improvement compared to patients who were randomized to receive KRYSTEXXA plus placebo (p<0.0001). An updated label would allow the Company’s commercial team to promote KRYSTEXXA plus methotrexate to physicians. The Prescription Drug User Fee Act (PDUFA) action date is July 7, 2022.

UPLIZNA Approved in Europe and China for NMOSD: In April, the European Commission approved UPLIZNA for the treatment of adult patients with neuromyelitis optica spectrum disorder (NMOSD) who are Anti-Aquaporin-4 Immunoglobulin G Seropositive (AQP4-IgG+). Germany is expected to be the first country where the Company initiates promotional and commercialization efforts in the EU. In March, the Company’s strategic partner Hansoh Pharmaceutical Group Company Limited received approval of UPLIZNA for the treatment of NMOSD from the National Medical Products Administration of the People’s Republic of China.

Advancing the Company’s Global Expansion with TEPEZZA and UPLIZNA Launch Preparations in Brazil: The Company initiated its build-out of primary infrastructure in Brazil to support the potential approvals of TEPEZZA for thyroid eye disease (TED) and UPLIZNA for NMOSD. There are no on-label treatments that are commercially available for TED or NMOSD in Brazil. Brazil marks the newest market that the company is pursuing as part of its global expansion strategy.
Initiated Enrollment in Two Clinical Trials:

In January, the first patient enrolled in a pivotal Phase 2b trial to evaluate HZN-825 in patients with idiopathic pulmonary fibrosis (IPF), the most common form of interstitial lung disease. IPF is a rare, progressive lung disease caused by inflammation and fibrosis, or scarring, of the lungs.

In February, the first patient enrolled in a Phase 3 trial in Japan to evaluate TEPEZZA in patients with moderate-to-severe active TED, a serious, progressive and potentially vision-threatening rare autoimmune disease. TEPEZZA has not been approved for commercial use in Japan.
Announced Positive Topline Proof-of-Concept Data from Dazodalibep Rheumatoid Arthritis Trial: In May, the Company announced positive topline results from the Phase 2 randomized placebo-controlled trial of dazodalibep in patients with RA. The primary endpoint of the trial was met across all doses, a statistically significant change from baseline in DAS28-CRP, a standardized measure of disease activity in RA trials, at Day 113. In addition, dazodalibep was well tolerated across all doses. The impact observed after various doses will inform the dosing regimen for other studies with dazodalibep.

Presented New UPLIZNA Data at Key Medical Meetings: In April, multiple new data were presented at the American Academy of Neurology (AAN) 2022 Annual Meeting, including new data from the Phase 3 trial showing no significant differences in attacks or Expanded Disability Status Scale (EDSS) worsening between NMOSD patients treated with UPLIZNA with one pre-study attack and those with two or more pre-study attacks. A separate new analysis of the Phase 3 trial showed long-term treatment with UPLIZNA improved pain and quality of life outcomes for at least three years. Additionally, new data from the Phase 3 trial were presented at the 48th Annual Meeting of the North American Neuro-Ophthalmology Society (NANOS 2022) in February, showing that treatment with UPLIZNA effectively reduced the severity of attacks in patients with NMOSD.

Presented New TEPEZZA Data at Key Medical Meeting: In February, multiple new data were presented at NANOS 2022, including new data from a post-marketing safety analysis of hearing-related events associated with TEPEZZA. Among the thousands of patients included in the analysis, approximately 10% of all cases reported to the safety database included a hearing-related event. This rate was similar to the rate in the Company’s initial trials. The majority of hearing-related adverse events in the pivotal trials and post-approval have been mild to moderate and reversible. No new safety concerns were observed in the post-marketing safety analysis.

New TEPEZZA Chronic TED Data Published: In January, new data from an independent physician case study of six chronic TED patients who showed benefit after treatment with TEPEZZA were published in Eye, the official journal for the Royal College of Ophthalmologists. The case study adds to the growing body of evidence supporting the use of TEPEZZA in chronic TED patients, with nearly 60 chronic TED patients across multiple case studies who have demonstrated benefit.

Expanding East Coast R&D and Technical Operations Hub: In January, the Company announced it entered into an agreement to lease a new 192,000-square-foot, state-of-the-art facility under construction in Rockville, Maryland that will serve as the Company’s primary East Coast research and development and technical operations hub. The Company is significantly expanding and consolidating its East Coast footprint with the new facility, nearly quadrupling its current Maryland footprint acquired in the 2021 acquisition of Viela. The Company anticipates adding key R&D talent to support its growing research and development capabilities and expanded pipeline.

Received Multiple Best Workplace Awards: In April, the Company was named one of Fortune’s "100 Best Companies to Work For" for the second consecutive year, retaining the highest ranked position in the biotechnology/pharmaceutical category. In March, Great Place to Work Ireland recognized Horizon as one of the "Best Workplaces in Ireland 2022" for the third consecutive year. These recognitions add to the many workplace awards the Company has received, reflecting the high level of engagement of its employees.

New President, Global Commercial Operations: The Company announced today that Jacopo Leonardi will join Horizon as president, global commercial operations, reporting to Tim Walbert, chairman, president and chief executive officer, effective May 16, 2022. Leonardi is an accomplished life sciences executive with more than two decades of commercial experience, which includes commercial launch, R&D new product planning as well as accelerating growth for high performing businesses in rare disease and immunology. Leonardi will oversee the U.S. and international commercial organizations, commercial development (life-cycle management) and global medical affairs.
Key Clinical Development Programs

Daxdilimab (HZN-7734), an anti-ILT7 human monoclonal antibody that depletes certain dendritic cells. Depleting these cells may interrupt the cycle of inflammation that causes tissue damage in diseases such as lupus, and a variety of other autoimmune conditions.

Systemic Lupus Erythematosus (SLE) Trial: Phase 2 randomized placebo-controlled trial underway to evaluate daxdilimab in patients with SLE, a disease in which the body’s immune system attacks its own tissues and organs.

Alopecia Areata Trial: Phase 2 trial to evaluate daxdilimab in patients with alopecia areata, an autoimmune disorder characterized by nonscarring hair loss, expected to initiate in the second quarter of 2022.

Discoid Lupus Erythematosus (DLE) Trial: Phase 2 trial to evaluate daxdilimab in patients with DLE, a rare, chronic, inflammatory skin condition characterized by lesions that result in scarring, expected to initiate by mid-year 2022.

Lupus Nephritis Trial: Phase 2 trial to evaluate daxdilimab in patients with lupus nephritis, a rare, autoimmune and inflammatory condition of the kidney, expected to initiate in the third quarter of 2022.

Dermatomyositis Trial: Phase 2 trial to evaluate daxdilimab in patients with dermatomyositis, a rare, autoimmune disorder characterized by rashes, debilitating muscle weakness and interstitial lung disease, expected to initiate in the fourth quarter of 2022.
Dazodalibep (HZN-4920), a CD40 ligand antagonist that blocks T-cell interaction with CD40-expressing B-cells, disrupting the overactivation of the CD40 ligand co-stimulatory pathway. Several autoimmune diseases are associated with the overactivation of this pathway.

Sjögren’s Syndrome Trial: Phase 2 randomized placebo-controlled trial underway to evaluate dazodalibep in patients with Sjögren’s syndrome, a chronic, systemic autoimmune condition that impacts exocrine glands, including the salivary and tear glands. The trial completed enrollment in April 2022.

Rheumatoid Arthritis Trial: Phase 2 randomized placebo-controlled trial to evaluate dazodalibep in patients with RA. Topline results were announced in May 2022. The trial met the primary endpoint and dazodalibep was well tolerated.

Kidney Transplant Rejection Trial: Phase 2 open-label trial underway to evaluate dazodalibep in kidney transplant rejection patients.

Focal Segmental Glomerulosclerosis (FSGS) Trial: Phase 2 trial to evaluate dazodalibep in patients with FSGS, a rare kidney disorder characterized by scarring of glomeruli, expected to initiate in the fourth quarter of 2022.
HZN-825, an oral lysophosphatidic acid receptor 1 (LPAR1) antagonist designed to prevent gene activation.

Diffuse Cutaneous Systemic Sclerosis Trial: Pivotal Phase 2b trial underway to evaluate HZN-825 in diffuse cutaneous systemic sclerosis.

Idiopathic Pulmonary Fibrosis Trial: Pivotal Phase 2b trial initiated in January 2022 to evaluate HZN-825 in idiopathic pulmonary fibrosis, the most common form of interstitial lung disease.
UPLIZNA, an anti-CD19 humanized monoclonal antibody that depletes B-cells, including the pathogenic cells that produce autoantibodies.

Myasthenia Gravis Trial: Phase 3 randomized placebo-controlled trial underway to evaluate UPLIZNA in patients with myasthenia gravis, a chronic, rare, autoimmune neuromuscular disease that affects voluntary muscles, especially those that control the eyes, mouth, throat and limbs.

IgG4-Related Disease Trial: Phase 3 randomized placebo-controlled trial underway to evaluate UPLIZNA in patients with IgG4-related disease, which is a group of disorders marked by tumor-like swelling and fibrosis of affected organs, such as the pancreas, salivary glands and kidneys.
TEPEZZA, an insulin-like growth factor type 1 receptor (IGF-1R) antagonist monoclonal antibody.

Chronic TED Trial: Phase 4 randomized placebo-controlled trial underway to evaluate TEPEZZA in chronic TED.

TED in Japan (OPTIC-J) Trial: Phase 3 randomized placebo-controlled trial in Japan initiated in February 2022 to evaluate TEPEZZA in patients with moderate-to-severe active TED.

Subcutaneous (SC) Administration Trial: Phase 1b trial to explore the pharmacokinetics, safety, tolerability, efficacy and immunogenicity of subcutaneous administration of TEPEZZA in patients with TED, expected to initiate by mid-year 2022.

Diffuse Cutaneous Systemic Sclerosis Exploratory Trial: Phase 1 exploratory trial underway to evaluate TEPEZZA in diffuse cutaneous systemic sclerosis.
KRYSTEXXA, a recombinant uricase enzyme that converts urate into a water-soluble liquid, allantoin, that can be easily excreted from the body.

Shorter Infusion Duration Trial: Phase 4 open-label trial underway to evaluate the impact of administering KRYSTEXXA plus methotrexate over a shorter infusion duration in patients with uncontrolled gout.

Monthly Dosing Trial: Phase 4 open-label trial underway to evaluate monthly dosing of KRYSTEXXA plus methotrexate in patients with uncontrolled gout.

Retreatment Trial: Phase 4 open-label trial underway to evaluate KRYSTEXXA plus methotrexate in patients who were not complete responders to KRYSTEXXA monotherapy.
HZN-1116, a fully human monoclonal antibody designed to bind and neutralize the function of the FLT3-ligand, thereby reducing both conventional and plasmacytoid dendritic cells.

Autoimmune Disease Trial: Phase 1 trial underway to evaluate HZN-1116 in patients with autoimmune diseases.
First-Quarter Financial Results

Note: For additional detail and reconciliation of non-GAAP financial measures to the most directly comparable GAAP financial measures, please refer to the tables at the end of this release.

Net Sales: First-quarter 2022 net sales were $885.2 million, an increase of 159% compared to the first quarter of 2021. First-quarter 2021 results were negatively impacted by a short-term TEPEZZA supply disruption due to U.S. government-mandated COVID 19-vaccine orders.

Gross Profit: Under U.S. GAAP, the first-quarter 2022 gross profit ratio was 75.7% compared to 70.7% in the first quarter of 2021. The non-GAAP gross profit ratio in the first quarter of 2022 was 88.9% compared to 90.9% in the first quarter of 2021.

Operating Expenses: R&D expenses were 11.7% of net sales and SG&A expenses were 42.1% of net sales in the first quarter of 2022. First-quarter non-GAAP R&D expenses were 10.4% of net sales and non-GAAP SG&A expenses were 37.1% of net sales.

Income Tax Expense (Benefit): On a GAAP basis in the first quarter of 2022, income tax benefit was $31.5 million. First-quarter non-GAAP income tax expense was $35.7 million.

Net Income: In the first-quarter of 2022, net income on a GAAP and non-GAAP basis was $204.3 million and $315.8 million, respectively.

Earnings (Loss) per Share: On a GAAP basis, diluted earnings (loss) per share in the first quarter of 2022 and 2021 were $0.87 and $(0.55). Non-GAAP diluted earnings per share in the first quarter of 2022 and 2021 were $1.34 and $0.02, respectively. Weighted average shares outstanding used for calculating GAAP and non-GAAP diluted earnings per share in the first quarter of 2022 were 236.0 million.
First-Quarter Segment Results

Management uses net sales and segment operating income to evaluate the performance of the Company’s two segments, the orphan segment and the inflammation segment. While segment operating income contains certain adjustments to the directly comparable GAAP figures in the Company’s consolidated financial results, such as the exclusion of upfront and milestone payments related to license and collaboration agreements, it is considered to be prepared in accordance with GAAP for purposes of presenting the Company’s segment operating results.

Orphan Segment Operating Income

First-quarter 2021 results were negatively impacted by a short-term TEPEZZA supply disruption due to U.S. government-mandated COVID 19-vaccine orders.

UPLIZNA was acquired on March 15, 2021. First-quarter 2022 UPLIZNA net sales included $5.2 million in revenue and milestone payments from the Company’s international partners.

First-quarter 2022 net sales of the orphan segment, the Company’s strategic growth segment, were $834.4 million, driven by the strong performance of TEPEZZA, KRYSTEXXA, RAVICTI, PROCYSBI, ACTIMMUNE and UPLIZNA. First-quarter 2022 orphan segment operating income was $351.5 million.

Inflammation Segment Operating Income

On Aug. 4, 2021, Alkem Laboratories, Inc. initiated an at-risk launch of generic DUEXIS in the United States.

First-quarter 2022 net sales of the inflammation segment were $50.9 million and segment operating income was $15.3 million.
Cash Flow Statement and Balance Sheet Highlights

First-quarter 2022 operating cash flow on a GAAP and non-GAAP basis was $215.8 million and $222.6 million, respectively.

As of March 31, 2022, the Company had cash and cash equivalents of $1.64 billion.

As of March 31, 2022, the total principal amount of debt outstanding was $2.60 billion.
2022 Guidance

The Company continues to expect full-year 2022 net sales to range between $3.9 billion and $4.0 billion, representing 22% growth at the midpoint. The Company continues to expect TEPEZZA full-year 2022 net sales percentage growth in the mid-30s and KRYSTEXXA full-year 2022 net sales growth of more than 20%. The Company continues to expect full-year 2022 adjusted EBITDA to range between $1.63 billion and $1.70 billion, representing 30% growth and 230 basis points of margin expansion at the midpoint.

Webcast

At 8 a.m. EDT / 1 p.m. IST today, the Company will host a live webcast to review its financial and operating results and provide a general business update. The live webcast and a replay may be accessed at View Source Please connect to the Company’s website at least 15 minutes prior to the live webcast to ensure adequate time for any software download that may be needed to access the webcast. A replay of the webcast will be available approximately two hours after the live webcast.