On May 5, 2022 AVEO Oncology (Nasdaq: AVEO), a commercial stage, oncology-focused biopharmaceutical company, reported financial results for the first quarter ended March 31, 2022 (Press release, AVEO, MAY 5, 2022, View Source [SID1234613670]).

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"We recently celebrated the one-year anniversary of our U.S. commercial launch of FOTIVDA (tivozanib). During the first quarter of 2022, we reported that, based on third party data, FOTIVDA had taken the leadership position in new patient starts for our targeted third-line relapsed or refractory advanced (R/R) renal cell carcinoma (RCC) population. This is a tremendous accomplishment, which we view as a leading indicator of progress towards our goal of becoming the overall market share leader and standard of care in the third-line R/R RCC setting, which we believe would in turn drive our continued growth. Based on what we have seen and heard to date, we continue to feel confident about our $100 million to $110 million full year 2022 FOTIVDA U.S. net product revenue guidance," stated Michael Bailey, President and Chief Executive Officer of AVEO. "In addition, with our Phase 3 TiNivo-2 trial evaluating tivozanib in combination with nivolumab underway, we are seeking to generate data to support regulatory approval of tivozanib (combined with nivolumab) in the larger second line R/R RCC market following prior immune checkpoint inhibitor therapy."

"Our team also continues to advance our pipeline of monoclonal antibodies. Collectively, we believe our commercial and clinical development activities offer exciting opportunities to improve patient care while also building long-term value for our shareholders," said Mr. Bailey.

First Quarter 2022 and Recent Highlights

Continued quarter over quarter growth of FOTIVDA U.S. net product revenue and prescriptions in Q1 2022.
First quarter 2022 U.S. net product revenue increased 20% to $20.1 million compared with U.S. net product revenue of $16.8 million in the fourth quarter of 2021, which reflects inventory shipped to distributors during the quarter and a gross-to-net estimate of 18.5% during the first quarter of 2022.
977 commercial prescriptions filled in the first quarter of 2022, representing a 25% increase from 780 commercial prescriptions filled in the fourth quarter of 2021.
FOTIVDA, based on third party data, has continued to hold its leadership position in the share of new patients starts in third-line R/R RCC for the first quarter. AVEO views new patient share starts as an important leading indicator of progress toward its objective to become the overall market share leader and the standard of care in the third-line R/R RCC setting.
Encouraging long-term follow up data for progression free survival (PFS) and overall survival (OS) from the Phase 3 TIVO-3 Clinical Trial of tivozanib in R/R advanced RCC patients were presented at the 2022 ASCO (Free ASCO Whitepaper) GU Cancers Symposium.
These new long-term PFS data from patients with five years of follow up further support the durable response and improved PFS previously observed in patients treated with FOTIVDA, including:
Landmark long-term PFS rates were consistently higher among patients treated with FOTIVDA as compared with patients treated with sorafenib (12% vs. 2% and 8% vs. 0% at three and four years, respectively), representing a clinically meaningful outcome for patients in the third- and fourth-line treatment setting.
Long-term OS was also analyzed and a non-significant trend favoring FOTIVDA continued to emerge with accumulation of events (HR 0.89).
Topline data for first-line cohort of the DEDUCTIVE trial were presented at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal (ASCO GI) Cancers Symposium.
New efficacy and safety data from the first line (cohort A) of the Phase 1b/2 clinical trial of tivozanib in combination with AstraZeneca’s IMFINZI (durvalumab) demonstrated a 28% partial response (PR) rate and disease control rate of 72% (PR plus stable disease) with a median PFS of 7.3 months and a 1-year OS of 76%. The data continues to support the efficacy and safety of tivozanib as an attractive vascular endothelial growth factor receptor inhibitor to use in combination with immune checkpoint inhibitors in first line metastatic hepatocellular carcinoma (HCC) patients.
The DEDUCTIVE trial is currently enrolling cohort B of second line patients after treatment with bevacizumab and atezolizumab. This cohort, which will enroll up to 20 subjects, has the potential to be the first clinical study to demonstrate benefit in the emerging population of HCC patients who have previously received immunotherapy.

Enrollment ongoing for Phase 3 TiNivo-2 Trial in R/R RCC following prior immunotherapy; Expect to complete enrollment in the first half of 2023.

AVEO continues to enroll patients in the Phase 3 TiNivo-2 clinical trial evaluating tivozanib in combination with nivolumab (OPDIVO), Bristol Myers Squibb’s antibody directed against PD-1, as compared with tivozanib monotherapy in patients with R/R RCC who have progressed following one or two lines of therapy, one of which was an immune checkpoint inhibitor. If successful, we believe data from this trial has the potential to support U.S. Food and Drug Administration (FDA) approval of tivozanib in combination with nivolumab in R/R RCC and expand the market opportunity for FOTIVDA into the larger second line R/R RCC setting. Bristol Myers Squibb is providing nivolumab clinical drug supply pursuant to a clinical trial collaboration and supply agreement. AVEO currently expects enrollment in the TiNivo-2 trial to be completed in the first half of 2023.
Secured clinical trial collaboration and supply agreement with NiKang Therapeutics, Inc. (NiKang) to evaluate tivozanib in combination with NKT2152.
On track to initiate a Phase 2 clinical trial to evaluate the safety and efficacy of tivozanib in combination with NKT2152, NiKang’s hypoxia inducible factor 2α (HIF2α), to treat clear cell RCC in mid-2022.
Started scale up activities for the manufacturing of ficlatuzumab clinical supply in the second quarter of 2022.
AVEO started scale up activities for the manufacturing of ficlatuzumab clinical supply in the second quarter of 2022 to enable the initiation of a potential registrational clinical trial in human papillomavirus (HPV) negative recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) in the first half of 2023. AVEO expects to continue to discuss the registrational pivotal clinical trial designs with the FDA and to continue to seek a strategic partner. In September 2021, AVEO announced that the FDA granted Fast Track designation for the investigation of the combination of ficlatuzumab and cetuximab for the treatment of patients with R/R HNSCC.
First Quarter 2022 Financial Highlights

At March 31, 2022, AVEO reported $79.0 million in cash, cash equivalents and marketable securities, as compared with $87.3 million at December 31, 2021.
Total revenue for the first quarter of 2022 was approximately $20.9 million compared with $1.9 million for the first quarter of 2021.
FOTIVDA U.S. net product revenue was $20.1 million for the first quarter of 2022 compared with $1.1 million for the first quarter of 2021.
Research and development expense for the first quarter of 2022 was $10.2 million compared with $5.8 million for the first quarter of 2021.
Selling, general and administrative expense for the first quarter of 2022 was $17.3 million compared with $15.1 million for the first quarter of 2021. The increase in selling, general and administrative expense for the first quarter 2022 is primarily due to a full quarter of costs associated with the commercial launch of FOTIVDA.
Net loss for the first quarter of 2022 was $10.2 million, or net loss of $0.30 per basic and diluted share, compared with a net loss of $22.1 million for the first quarter of 2021, or net loss of $0.81 per basic and diluted share.
Financial Guidance

AVEO believes that its $79.0 million in cash, cash equivalents and marketable securities as of March 31, 2022, along with expected net product revenues from the sales of FOTIVDA in the United States, will enable AVEO to maintain its current operations for a period of more than 12 months from the date of filing of its Quarterly Report on Form 10-Q for the quarter ended March 31, 2022.

AVEO currently expects to achieve full year 2022 FOTIVDA U.S. net product revenues between $100.0 million and $110.0 million. AVEO expects that commercial expenses will be approximately $50.0 million in 2022. AVEO expects general and administrative expenses will remain at approximately $20.0 million for the year. Research and development expenses are expected to be in the range of $60.0 million to $70.0 million in 2022 in support of AVEO’s existing pipeline plans. In addition, AVEO expects that gross margins will continue to be in the mid-to-high 80th percentile in 2022.

Conference Call and Webcast

In connection with this announcement, AVEO will host a conference call and audio webcast today, May 5, 2022, at 8:30 A.M. Eastern Time. The call can be accessed by dialing (800) 954-1051 (U.S. and Canada) or (303) 223-0117 (international). The passcode for the conference call is 22018215. To access the live webcast, or the subsequent archived recording, please visit the Calendar of Events sub-section within the Investors section of the AVEO website at www.aveooncology.com.

About FOTIVDA (tivozanib)

FOTIVDA (tivozanib) is an oral, next-generation vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI). It is a potent, selective inhibitor of VEGFRs 1, 2, and 3 with a long half-life designed to improve efficacy and tolerability. AVEO received U.S. Food and Drug Administration (FDA) approval for FOTIVDA on March 10, 2021 for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies. FOTIVDA was approved in August 2017 in the European Union and other countries in the territory of its partner EUSA Pharma (UK) Limited for the treatment of adult patients with advanced RCC. FOTIVDA has been shown to significantly reduce regulatory T-cell production in preclinical models.1 FOTIVDA was discovered by Kyowa Kirin.

INDICATIONS

FOTIVDA is indicated for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hypertension and Hypertensive Crisis: Control blood pressure prior to initiating FOTIVDA. Monitor for hypertension and treat as needed. For persistent hypertension despite use of anti-hypertensive medications, reduce the FOTIVDA dose.

Cardiac Failure: Monitor for signs or symptoms of cardiac failure throughout treatment with FOTIVDA.

Cardiac Ischemia and Arterial Thromboembolic Events: Closely monitor patients who are at increased risk for these events. Permanently discontinue FOTIVDA for severe arterial thromboembolic events, such as myocardial infarction and stroke.

Venous Thromboembolic Events: Closely monitor patients who are at increased risk for these events. Permanently discontinue FOTIVDA for severe venous thromboembolic events.

Hemorrhagic Events: Closely monitor patients who are at risk for or who have a history of bleeding.

Proteinuria: Monitor throughout treatment with FOTIVDA. For moderate to severe proteinuria, reduce the dose or temporarily interrupt treatment with FOTIVDA.

Thyroid Dysfunction: Monitor before initiation and throughout treatment with FOTIVDA.

Risk of Impaired Wound Healing: Withhold FOTIVDA for at least 24 days before elective surgery. Do not administer for at least 2 weeks following major surgery and adequate wound healing. The safety of resumption of FOTIVDA after resolution of wound healing complications has not been established.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): Discontinue FOTIVDA if signs or symptoms of RPLS occur.

Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception.

Allergic Reactions to Tartrazine: The 0.89 mg capsule of FOTIVDA contains FD&C Yellow No.5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible patients.

ADVERSE REACTIONS
The most common (≥20%) adverse reactions were fatigue, hypertension, diarrhea, decreased appetite, nausea, dysphonia, hypothyroidism, cough, and stomatitis, and the most common Grade 3 or 4 laboratory abnormalities (≥5%) were sodium decreased, lipase increased, and phosphate decreased.

DRUG INTERACTIONS

Strong CYP3A4 Inducers: Avoid coadministration of FOTIVDA with strong CYP3A4 inducers.

USE IN SPECIFIC POPULATIONS

Lactation: Advise not to breastfeed.
Females and Males of Reproductive Potential: Can impair fertility.
Hepatic Impairment: Adjust dosage in patients with moderate hepatic impairment. Avoid use in patients with severe hepatic impairment.

About Advanced Renal Cell Carcinoma

According to the American Cancer Society’s 2021 statistics, renal cell carcinoma (RCC) is the most common type of kidney cancer, which is among the ten most common cancers in both men and women. Approximately 73,750 new cases of kidney cancer will be diagnosed annually and about 14,830 people will die from this disease. In patients with late-stage disease, the five-year survival rate is 13%. Agents that target the vascular endothelial growth factor (VEGF) pathway have shown significant antitumor activity in RCC.2 According to a 2019 publication, 50% of the approximately 10,000 patients who progress following two or more lines of therapy choose not to receive further treatment,3 which may be attributable to tolerability concerns and a lack of data to support evidence-based treatment decisions in this highly relapsed or refractory patient population.

On May 5, 2022 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported financial results for the quarter ended March 31, 2022 (Press release, Karyopharm, MAY 5, 2022, View Source [SID1234613669]). In addition, Karyopharm highlighted select corporate milestones, including details regarding the ongoing U.S. commercialization of XPOVIO (selinexor) and provided an overview of its key clinical development programs.

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"During the first quarter of 2022, we continued to drive further patient benefit by expanding the use of XPOVIO in the 2nd to 4th line setting and, despite headwinds caused by the Omicron variant, we achieved strong XPOVIO sales of 30% year-over-year growth," said Richard Paulson, President and Chief Executive Officer of Karyopharm. "As we advance our clinical pipeline across four core priority areas, we look forward to presenting the preliminary results from our Phase 1/2 frontline myelofibrosis study and initiating our Phase 3 study in the p53 wild-type endometrial cancer patient population in the second half of 2022, both areas with significant unmet need."

First Quarter 2022 and Recent Highlights

XPOVIO Commercial Performance

Achieved U.S. net product revenue for the first quarter of 2022 of $28.3 million, a 30% increase compared to the first quarter of 2021.
COVID related impact in January and February on oncology patient visits, which improved in March.
Continued positive shift in patients to earlier lines from the penta-refractory setting.
Recent regulatory approvals in Australia and Singapore received by partner Antengene Therapeutics Limited further expands selinexor’s reach to patients around the world, following approval in Mainland China in December 2021.
R&D Highlights for Selinexor and Eltanexor

Abstracts highlighting selinexor clinical research have been selected for presentation at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2022 Annual Meeting during June 3-7, 2022, including a poster presentation highlighting preliminary results from a Phase 1/2 trial evaluating selinexor in combination with ruxolitinib in patients with treatment-naïve myelofibrosis and an oral presentation discussing subgroup analyses and molecular classification data from the Phase 3 SIENDO study evaluating selinexor in endometrial cancer.
Results from the prospective double-blind, randomized Phase 3 SIENDO study of oral selinexor versus placebo as maintenance therapy after first-line chemotherapy for advanced or recurrent endometrial cancer were presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper)’s Virtual Plenary and the Society for Gynecologic Oncology 2022 Annual Meeting on Women’s Cancer in March 2022.
In a preliminary analysis of a pre-specified, exploratory sub-group of patients with advanced or recurrent p53 wild-type endometrial cancer in the SIENDO trial, a 10 month improvement in median progression free survival was observed with selinexor versus placebo: 13.7 months in the selinexor arm (n=67) vs 3.7 months in the placebo arm (n=36).
The Company plans to initiate a new randomized, placebo-controlled clinical study of selinexor in patients with p53 wild-type endometrial cancer during the second half of 2022 and top-line data are expected to be available in the first half of 2024.
The U.S. Food and Drug Administration (FDA) granted orphan drug designation for eltanexor for the treatment of myelodysplastic syndromes (MDS). The Company is currently evaluating the use of eltanexor in a Phase 2 study as monotherapy in hypomethylating agent (HMA)-refractory, intermediate or high-risk MDS and also exploring its use in combination with HMA therapy in newly diagnosed patients in a Phase 1 study.
The application for NEXPOVIO️ (selinexor) in combination with Velcade️ (bortezomib) and low-dose dexamethasone for the treatment of multiple myeloma following at least one prior therapy, is currently under review by the Committee for Medicinal Products for Human Use (CHMP). The CHMP is expected to issue an opinion to the European Commission in the first half of 2022.
Corporate and Business Highlights

Announced the appointment of Reshma Rangwala, MD, PhD, as Chief Medical Officer.
Announced the further transition of company co-founders Sharon Shacham, PhD, MBA, and Michael Kauffman, MD, PhD, who will step down from their respective roles as Chief Scientific Officer and Senior Clinical Advisor as of May 31, 2022. Dr. Shacham will continue to serve on Karyopharm’s Scientific Advisory Board and will serve in an advisory capacity.
First Quarter 2022 Financial Results

Total Revenues: Total revenue for the first quarter of 2022 was $47.7 million, up 105% compared to $23.3 million for the first quarter of 2021.

Net product revenue: Net product revenue for the first quarter of 2022 was $28.3 million, up 30% compared to $21.7 million for the first quarter of 2021.

License and other revenue: License and other revenue for the first quarter of 2022 was $19.4 million, compared to $1.5 million for the first quarter of 2021. The increase in license and other revenue in the first quarter of 2022 compared to the first quarter of 2021 was primarily attributable to $8.6 million in revenue recognized related to milestones earned in connection with our license agreements with Antengene Therapeutics Limited and Promedico Ltd., coupled with $7.1 million earned in reimbursement of development expenses from the Menarini Group.

Cost of sales: Cost of sales for the first quarter of 2022 were $1.4 million, compared to $0.9 million for the first quarter of 2021. Cost of sales reflects the costs of XPOVIO units sold and third-party royalties on net product revenue.

Research and development (R&D) expenses: R&D expenses for the first quarter of 2022 were $42.1 million, compared to $37.1 million for the first quarter of 2021. The increase in R&D expenses in the first quarter of 2022 compared to the first quarter of 2021 was primarily attributable to higher clinical trial expenses.

Selling, general and administrative (SG&A) expenses: SG&A expenses for the first quarter of 2022 were $38.8 million, compared to $37.7 million for the first quarter of 2021.

Interest expense: Interest expense for the first quarter of 2022 was $6.7 million, compared to $5.1 million for the first quarter of 2021. The increase in interest expense in the first quarter of 2022 compared to the first quarter of 2021 was related to the deferred royalty obligation following Karyopharm’s June 2021 amendment of its Revenue Interest Agreement with HealthCare Royalty Management, LLC.

Net loss: Karyopharm reported a net loss of $41.4 million, or $0.53 per share, for the first quarter of 2022, compared to a net loss of $57.4 million, or $0.77 per share, for the first quarter of 2021. Net loss included non-cash stock-based compensation expense of $7.3 million and $7.4 million for the first quarters of 2022 and 2021, respectively.

Cash position: Cash, cash equivalents, restricted cash and investments as of March 31, 2022 totaled $207.0 million, compared to $235.6 million as of December 31, 2021.

2022 Financial Outlook

Based on its current operating plans, Karyopharm reaffirms the following for full year 2022:

XPOVIO net product revenue to be in the range of $135 million to $145 million.
Non-GAAP R&D and SG&A expenses, excluding stock-based compensation expense, for the year ending December 31, 2022, to be in the range of $265 million to $280 million. Karyopharm has not reconciled the full year 2022 outlook for non-GAAP R&D and SG&A expenses to full year 2022 outlook for GAAP R&D and SG&A expenses because Karyopharm cannot reliably predict without unreasonable efforts the timing or amount of the factors that substantially contribute to the projection of stock compensation expense, which is excluded from the full year 2022 outlook for non-GAAP R&D and SG&A expenses.
The Company expects that its existing cash, cash equivalents and investments, and the revenue it expects to generate from XPOVIO product sales, as well as revenue generated from its license agreements, will be sufficient to fund its planned operations into early 2024.
Non-GAAP Financial Information

Karyopharm uses a non-GAAP financial measure, including R&D and SG&A expenses, to provide operating expense guidance. Non-GAAP R&D and SG&A expenses exclude stock-based compensation expense. Karyopharm believes this non-GAAP financial measure is useful to investors because it provides greater transparency regarding Karyopharm’s operating performance as it excludes non-cash stock compensation expense. This non-GAAP financial measure should not be considered a substitute or an alternative to GAAP R&D and SG&A expenses and should not be considered a measure of Karyopharm’s liquidity. Instead, non-GAAP R&D and SG&A expenses should only be used to supplement an understanding of Karyopharm’s operating results as reported under GAAP.

Conference Call Information

Karyopharm will host a conference call today, May 5, 2022, at 8:30 a.m. Eastern Time, to discuss the first quarter 2022 financial results and provide other business highlights. To access the conference call, please dial (888) 349-0102 (local) or (412) 902-4299 (international) at least 10 minutes prior to the start time and ask to be joined into the Karyopharm Therapeutics call. A live audio webcast of the call, along with accompanying slides, will be available under "Events & Presentations" in the Investor section of the Company’s website, View Source An archived webcast will be available on the Company’s website approximately two hours after the event.

About XPOVIO (selinexor)

XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor and the first of Karyopharm’s Selective Inhibitor of Nuclear Export (SINE) compounds to be approved for the treatment of cancer. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein XPO1. XPOVIO is approved in the U.S. and marketed by Karyopharm in multiple oncology indications, including: (i) in combination with Velcade (bortezomib) and dexamethasone (XVd) in patients with multiple myeloma after at least one prior therapy; (ii) in combination with dexamethasone in patients with heavily pre-treated multiple myeloma; and (iii) in patients with diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. XPOVIO (also known as NEXPOVIO in certain countries) has received regulatory approvals in a growing number of ex-U.S. territories and countries, including Europe, the United Kingdom, China, South Korea and Israel, and is marketed in those areas by Karyopharm’s global partners. Selinexor is also being investigated in several other mid- and late-stage clinical trials across multiple high unmet need cancer indications, including in endometrial cancer and myelofibrosis.

For more information about Karyopharm’s products or clinical trials, please contact the Medical Information department at:

Tel: +1 (888) 209-9326
Email: [email protected]

XPOVIO (selinexor) is a prescription medicine approved:

In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (XVd).
In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti‐CD38 monoclonal antibody (Xd).
For the treatment of adult patients with relapsed or refractory diffuse large B‐cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
SELECT IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care.
Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony‐stimulating factors.
Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care.
Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care.
Serious Infection: Monitor for infection and treat promptly.
Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes.
Embryo‐Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception.
Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract.
Adverse Reactions

The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3‐4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%.
The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.
The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3‐4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal adverse reactions was infection (4.5% of patients). Serious adverse reactions occurred in 46% of patients; the most frequent serious adverse reaction was infection (21% of patients). Discontinuation due to adverse reactions occurred in 17% of patients.

On May 5, 2022 Synlogic, Inc. (Nasdaq: SYBX), a clinical-stage biotechnology company developing medicines for metabolic and immunological diseases through its proprietary approach to synthetic biology, reported the Company will release its first quarter 2022 financial results before the market opens on Thursday, May 12, 2022 (Press release, Synlogic, MAY 5, 2022, View Source [SID1234613668]). The press release will be followed by a conference call at 8:30 am ET, which will be open to the public via telephone and webcast. During the conference call, the Company will review its financial results and provide a business update.

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The conference call dial-in numbers are (844) 815-2882 for domestic callers and (213) 660-0926 for international callers. The conference ID number for the call is 5149412. Participants may access the live webcast in the "Events Calendar" of the Investors & Media section

On May 5, 2022 Agios Pharmaceuticals, Inc. (NASDAQ: AGIO), a leader in the field of cellular metabolism pioneering therapies for genetically defined diseases, reported business highlights and financial results for the first quarter ended March 31, 2022 (Press release, Agios Pharmaceuticals, MAY 5, 2022, View Source [SID1234613667]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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"The U.S. approval of PYRUKYND in adults with PK deficiency was Agios’ first step toward changing treatment paradigms for people with genetically defined diseases, starting with developing the first disease-modifying therapy for a rare, debilitating, lifelong hemolytic anemia," said Jackie Fouse, Ph.D., chief executive officer at Agios. "We are now poised to expand our impact for many more patients, including adults with PK deficiency in the EU, pediatric PK deficiency patients and people living with thalassemia, sickle cell disease and low- to intermediate-risk myelodysplastic syndrome. I am tremendously proud of our team’s incredible work on the U.S. launch of PYRUKYND, ongoing regulatory interactions in the EU, five pivotal clinical trials planned or underway, the expansion of our PK activation portfolio with AG-946 and our innovative research engine. We continue to execute in each of these arenas, motivated and inspired by our connections to patients."

First Quarter 2022 & Recent Highlights

Received approval from the U.S. Food and Drug Administration (FDA) for PYRUKYND, the first therapy for the treatment of hemolytic anemia in adults with PK deficiency and Agios’ first genetically defined disease medicine.
Executed commercial launch of PYRUKYND and generated approximately $0.8 million in net U.S. revenue for the first partial quarter following launch.
Published results from the ACTIVATE Phase 3 clinical study evaluating PYRUKYND in adults with PK deficiency who do not receive regular transfusions in the New England Journal of Medicine.
Completed the single ascending dose and multiple ascending dose healthy volunteer cohorts of the Phase 1 study of novel PK activator AG-946 and identified doses for the Phase 1 sickle cell disease cohort and Phase 2a study in low- to intermediate risk myelodysplastic syndrome (MDS).
Initiated the sickle cell disease cohort of the Phase 1 study of AG-946.
Published 2022 Environmental, Social and Governance (ESG) Report disclosing ESG initiatives and metrics aligned with the United Nations Sustainable Development Goals (UN SDGs) and the standards for the Biotechnology and Pharmaceuticals industry set by the Sustainability Accounting Standards Board (SASB).
Key Upcoming Milestones & Priorities

Agios expects to execute on the following key milestones and priorities in 2022:

Adult PK Deficiency: Receive European Medicines Agency (EMA) regulatory decision for PYRUKYND in adults with PK deficiency by year-end.
Pediatric PK Deficiency: Initiate Phase 3 ACTIVATE-kids and ACTIVATE-kidsT studies of PYRUKYND in not regularly transfused and regularly transfused pediatric patients with PK deficiency, respectively, in mid-2022.
Thalassemia: Enroll a meaningful portion of patients in the Phase 3 ENERGIZE and ENERGIZE-T studies of PYRUKYND in not regularly transfused and regularly transfused adults with thalassemia, respectively, by year-end.
Sickle Cell Disease: Complete enrollment in the Phase 2 portion of the RISE UP study of PYRUKYND in sickle cell disease by year-end.
Myelodysplastic Syndrome: Initiate Phase 2a study of AG-946 in adults with low- to intermediate-risk MDS by year-end.
Data Presentations

Submitted new clinical and translational data to the European Hematology Association (EHA) (Free EHA Whitepaper) congress, to be held June 9-12 in Vienna and virtually, including:
New patient-reported outcomes (PRO) data from ACTIVATE Phase 3 study of PYRUKYND
Data demonstrating the normalization of hemoglobin levels with long-term treatment of PYRUKYND in adults with PK deficiency
Additional PK deficiency comorbidities and complications data from the PEAK registry
Continue to publish clinical and translational data supporting the utility of PK activators across key disease areas and elucidating the burden of disease for PK deficiency, thalassemia and sickle cell disease.
First Quarter 2022 Financial Results

The financial results discussion compares Agios’ continuing operations. All periods have been adjusted to exclude discontinued operations related to the divested oncology business.

Revenue: Net U.S. product revenue from sales of PYRUKYND for the first quarter of 2022 was $0.8 million. This revenue reflects the first partial quarter of PYRUKYND launch, following FDA approval on February 17, 2022.

Cost of Sales: Cost of sales for the first quarter of 2022 were $0.3 million.

Non-Operating Income: Non-operating income included approximately $2.7 million from TIBSOVO (ivosidenib) royalties for the first quarter of 2022.

Research and Development (R&D) Expenses: R&D expenses were $70.1 million for the first quarter of 2022 compared to $57.7 million for the first quarter of 2021. The year-over-year increase in R&D was driven primarily by start-up costs for the PYRUKYND pivotal studies in thalassemia and sickle cell disease and planned increases in research activities, offset by closeouts of the ACTIVATE and ACTIVATE-T studies.

Selling, General and Administrative (SG&A) Expenses: SG&A expenses were $31.5 million for the first quarter of 2022 compared to $33.6 million for the first quarter of 2021. The year-over-year decrease in SG&A expenses was primarily attributable to lower workforce expenses.

Net Loss from Continuing Operations: Net loss from continuing operations was $94.8 million for the first quarter of 2022 compared to a net loss of $90.9 million for the first quarter of 2021.

Cash Position and Guidance: Cash, cash equivalents and marketable securities as of March 31, 2022, were $1.2 billion compared to $2.4 billion as of March 31, 2021. The year-over-year decrease is attributable to operating expenses and 16.2 million shares of common stock that the company repurchased for $802.5 million during the second through fourth quarters of 2021. Agios expects that its cash, cash equivalents and marketable securities will enable the company to execute its operating plan through major catalysts and to cash-flow positivity without the need to raise additional equity.

Conference Call Information
Agios will host a conference call and live webcast with slides today at 8:00 a.m. ET to discuss first quarter 2022 financial results and recent business activities. To participate in the conference call, please dial 1-877-377-7098 (domestic) or 1-631-291-4547 (international) and refer to conference ID 5738266. The live webcast can be accessed under "Events & Presentations" in the Investors section of the company’s website at www.agios.com. The archived webcast will be available on the company’s website beginning approximately two hours after the event.

On May 5, 2022 Cardinal Health (NYSE: CAH) reported third quarter fiscal year 2022 revenues of $44.8 billion, an increase of 14% from the third quarter of last year (Press release, Cardinal Health, MAY 5, 2022, View Source [SID1234613666]). Third quarter GAAP operating loss was $97 million, due to a non-cash, pre-tax goodwill impairment of $474 million in the Medical segment. GAAP diluted loss per share was $5.05, primarily due to this impairment, net of tax effects. Third quarter non-GAAP operating earnings decreased 21% to $545 million, primarily due to inflationary impacts and global supply chain constraints in the Medical segment. Non-GAAP diluted earnings per share (EPS) decreased 5% to $1.45, reflecting the change in non-GAAP operating earnings, partially offset by a lower non-GAAP effective tax rate and share count.

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Cardinal Health, Inc. is a global, integrated healthcare services and products company, providing customized solutions for hospitals, healthcare systems, pharmacies, ambulatory surgery centers, clinical laboratories and physician offices worldwide. (PRNewsfoto/Cardinal Health)

"While we’re taking action to drive performance across all our businesses, particularly the Medical segment, our third quarter results reflect continued inflationary impacts and global supply chain constraints," said Mike Kaufmann, chief executive officer of Cardinal Health. "We have updated our outlook for Medical to reflect the challenging environment, and reiterated our outlook for the Pharmaceutical segment in fiscal year 2022. Going forward, we remain confident in our ability to drive sustainable, long-term growth."

Third-quarter revenue for the Pharmaceutical segment increased 17% to $41.0 billion, driven by branded pharmaceutical sales growth from existing and net new Pharmaceutical Distribution and Specialty customers.

Pharmaceutical segment profit decreased 5% to $487 million in the third quarter, driven by higher operations expenses and previously anticipated investments in technology enhancements, partially offset by generics program performance.

Medical segment

Third-quarter revenue for the Medical segment decreased 7% to $3.9 billion, due to the divestiture of the Cordis business and lower products and distribution volumes, which includes the impact of global supply chain constraints.

Medical segment profit decreased 66% to $59 million in the third quarter, primarily due to net inflationary impacts and global supply chain constraints in products and distribution.

Opioid lawsuits developments

Cardinal Health, along with pharmaceutical distribution peers, finalized the previously announced national opioid settlement agreement (the "National Settlement"), which became effective on April 2, 2022. 46 of 49 eligible states, Washington DC, all eligible territories, and greater than 98 percent of litigating political subdivisions are participating in the National Settlement. This comprehensive agreement will settle the vast majority of the opioid lawsuits filed by state and local governmental entities. Under the National Settlement, the Company will pay participating states and subdivisions up to $6.0 billion2, the majority of which will be paid over 18 years. The settlement also includes injunctive relief terms related to distributors’ controlled substance anti-diversion programs, which are designed in part to provide increased transparency within the supply chain. As part of the injunctive relief terms, the distributors will engage a third-party vendor to act as a clearinghouse for data aggregation and reporting. Additional injunctive relief provisions include terms related to the training of controlled substance monitoring program employees, due diligence for new and existing customers, ordering limits for certain products and suspicious order monitoring.

Additionally, in May 2022, Cardinal Health, along with pharmaceutical distribution peers, reached an agreement with the State of Washington to resolve the opioid-related claims of the state and its participating subdivisions. Under this agreement, we will pay up to approximately $160 million, which is consistent with the amount that would have been allocated to Washington under the National Settlement, plus certain attorneys’ fees and costs. The payments will be made on timelines and terms consistent with the National Settlement. This agreement is subject to certain contingencies, including the rate of subdivision participation.

"These settlements are an important step forward for our company," said Kaufmann. "This is a significant milestone towards achieving broad resolution of governmental opioid claims and delivering meaningful relief to communities across the United States."

Fiscal year 2022 outlook1

The company updated its fiscal year 2022 guidance range for non-GAAP diluted earnings per share attributable to Cardinal Health, Inc. to $5.15 to $5.25, from $5.15 to $5.50.

The company also updated Medical segment profit outlook to a forty-five to fifty-five percent decline, from a thirty to forty-five percent decline. The fiscal year 2022 outlook for Medical segment profit includes a year-over-year net incremental headwind of nearly $300 million due to inflationary and global supply chain constraint impacts.

In addition to the updated Medical segment profit outlook, the new non-GAAP EPS guidance range reflects updated expectations3 for fiscal year 2022 non-GAAP effective tax rate of 22% to 23%, diluted weighted average shares outstanding of approximately 281 million, and capital expenditures of approximately $400 million.

The company does not provide forward-looking guidance on a GAAP basis as certain financial information, the probable significance of which cannot be determined, is not available and cannot be reasonably estimated. See "Use of Non-GAAP Measures" following the attached schedules for additional explanation.

Tax rate

During the third quarters of fiscal 2022 and 2021, GAAP effective tax rates were (916.5%) and 72.8%, respectively. The GAAP effective tax rate for the third quarter of fiscal 2022 included the impact of non-cash, pre-tax goodwill impairments of $1.8 billion in the Medical segment in fiscal 2022, which significantly decreased the estimated annual effective tax rate for fiscal year 2022. Applying the lower tax rate to the year-to-date loss resulted in recognizing an interim tax expense in the quarter of approximately $1.2 billion. The GAAP effective tax rate in the third quarter of fiscal 2021 reflected the tax effect of the litigation charge incurred in the first quarter of fiscal 2021.

The third quarter fiscal 2022 and 2021 non-GAAP effective tax rates of 20.1% and 31.2%, respectively, reflect the impact of certain discrete items. Third quarter fiscal 2021 effective tax rates also reflect the resolution of all open issues with the IRS for fiscal years 2008 to 2010 as well as certain transfer pricing matters for fiscal years 2011 to 2014.

Recent highlights

Cardinal Health announced plans to build a new 574,670 square foot medical distribution center in the central Ohio area, replacing a smaller nearby facility. The new, larger building will improve service and quality, deliver operational efficiencies, and better support fluctuations in volume and labor.
Cardinal Health plans to build a new manufacturing facility dedicated to increasing the supply of Protexis brand gloves, driving further growth in the surgical glove portfolio.
Cardinal Health partnered with Innara Health, the industry leader in feeding development for newborns and premature infants, to design Innara’s next generation NTrainer System, making it smaller, more intuitive, and easier to integrate into NICU feeding protocols.
Cardinal Health launched the first surgical incise drape using Avery Dennison’s patented BeneHoldTM CHG adhesive, which reduces the risk of surgical site contamination, yet still removes easily after surgery without harming a patient’s skin.
Cardinal Health partnered with Kinaxis to optimize digital supply chain planning and increase supply chain agility and medical product visibility to patients, with initial implementation in at-Home Solutions. Kinaxis’s Rapid ResponseTM platform supports fast, confident decisions using advanced insights and analytics in real time.
Forbes named Cardinal Health one of America’s Best Large Employers 2022.
Upcoming webcasted investor events

UBS Global Healthcare Conference at 8:30 a.m. EST, May 25, 2022
Webcast

Cardinal Health will host a webcast today at 8:30 a.m. Eastern to discuss third-quarter results. To access the webcast and corresponding slide presentation, go to the Investor Relations page at ir.cardinalhealth.com. No access code is required.

Presentation slides and a webcast replay will be available until May 4, 2023.