On November 3, 2022 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported business highlights and financial results for the quarter ended September 30, 2022 (Press release, Karyopharm, NOV 3, 2022, View Source [SID1234622967]).
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"We had a highly productive third quarter executing against our key priorities which delivered strong growth in patient demand and product revenues. We also achieved an important milestone this quarter with the initiation of the pivotal Phase 3 study evaluating selinexor as a maintenance therapy in women with TP53 wild-type endometrial cancer and anticipate sharing topline results in 2024," said Richard Paulson, President and Chief Executive Officer of Karyopharm. "Today, our abstracts were released for the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, including encouraging data from the Phase 1 study evaluating selinexor in combination with ruxolitinib in patients with treatment-naïve myelofibrosis, which continues to demonstrate promising activity in key efficacy endpoints. We look forward to sharing further updated results from this study at the ASH (Free ASH Whitepaper) meeting in December."
Third Quarter 2022 and Recent Highlights
XPOVIO Commercial Performance
Achieved U.S. net product revenue for the third quarter of 2022 of $32.0 million, a 20% increase compared to the third quarter of 2021, driven by growth in new patient starts and refills.
XPOVIO continued its growth in the community setting, driven by the continued shift of XPOVIO into second to fourth lines of therapy and increasing confidence in the perception of the product.
Increased selinexor’s reach with the commercial launch of NEXPOVIO by the Company’s partner, Menarini Group, in Germany and Austria.
Research & Development (R&D) Highlights for Selinexor and Eltanexor
Initiated a global, randomized, double-blind Phase 3 study evaluating selinexor as maintenance therapy for patients with TP53 wild-type advanced or recurrent endometrial cancer. The study will utilize Foundation Medicine’s tissue-based next generation sequencing test to identify and enroll patients whose tumors are TP53 wild-type. Top-line results from the study are anticipated in 2024.
Results from the Phase 1 study evaluating selinexor in combination with ruxolitinib in patients with treatment-naïve myelofibrosis (NCT:04562389) have been accepted for poster presentation at the ASH (Free ASH Whitepaper) 2022 Annual Meeting. The data included in the abstract for ASH (Free ASH Whitepaper) 2022 were based on the Phase 1 portion of the Phase 1/2 study evaluating the safety and preliminary efficacy of once-weekly selinexor in combination with standard dose ruxolitinib in patients with treatment-naïve myelofibrosis (NCT04562389). As of July 2022, 19 patients had been assigned to either selinexor 40 mg or 60 mg, in combination with ruxolitinib 15/20 mg BID. 79% (11 out of 14) and 86% (6 out of 7) of efficacy evaluable patients demonstrated ≥35% reduction in spleen volume (SVR 35) at week 12 and at week 24, respectively. 69% (9 out of 13) of efficacy evaluable patients evidenced a ≥50% reduction (TSS50) at week 12 and 65% (11 out of 17) of transfusion-independent patients who had at least eight weeks of treatment maintained stable hemoglobin (± 2g/dL) or improved hemoglobin level (>2g/dL increase) at last follow up. The data observed across both 40mg and 60mg doses demonstrate a generally manageable side effect profile with no dose limiting toxicities at either dose level in the Phase 1a dose escalation with the most common adverse events (AEs) being nausea (58%), anemia (42%) and vomiting (42%), the majority of which were grades 1-2, and the most commonly reported grades 3-4 treatment-emergent AEs being thrombocytopenia (26%) and anemia (21%), which were reversible. Updated data from this study, including results from additional patients, will be presented at the ASH (Free ASH Whitepaper) meeting in December 2022.
The European Commission adopted the Committee for Orphan Medicinal Products opinion to designate selinexor as an orphan medicinal product for the treatment of myelofibrosis, and eltanexor as an orphan medicinal product for the treatment of myelodysplastic syndromes (MDS), in the European Union in October 2022 and July 2022, respectively.
FDA granted Fast Track Designation for the development program of eltanexor as monotherapy for the treatment of patients with relapsed or refractory intermediate, high-, or very high-risk MDS per IPSS-R in July 2022.
2022 Financial Guidance
Based on its current operating plans, Karyopharm is maintaining its guidance for the full year 2022:
Total revenue to be in the range of $155 million to $165 million.
XPOVIO net product revenue to be in the range of $120 million to $130 million.
Non-GAAP R&D and Selling, general and administrative (SG&A) expenses, excluding stock-based compensation expense, to be in the range of $250 million to $265 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 continues to expect 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.
Third Quarter 2022 Financial Results
Total Revenue: Total revenue for the third quarter of 2022 was $36.1 million, down 4% compared to $37.7 million for the third quarter of 2021.
Net product revenue: Net product revenue for the third quarter of 2022 was $32.0 million, up 20% compared to $26.7 million for the third quarter of 2021.
License and other revenue: License and other revenue for the third quarter of 2022 was $4.1 million, compared to $11.0 million for the third quarter of 2021. The decrease was primarily attributable to the recognition of $9.8 million in milestone-related revenue from Antengene Therapeutics Limited (Antengene) in the third quarter of 2021, compared to $2.4 million in royalty revenue and $1.4 million in reimbursement revenue from Menarini recognized in the third quarter of 2022.
Cost of sales: Cost of sales for the third quarter of 2022 were $1.0 million, compared to $0.6 million for the third quarter of 2021. Cost of sales includes the costs of producing and distributing XPOVIO units sold and third-party royalties on net product revenue.
R&D expense: R&D expense for the third quarter of 2022 were $31.4 million, compared to $45.8 million for the third quarter of 2021. The decrease was primarily driven by the recognition of $7.4 million of costs in connection with the acquisition of certain assets from Neumedicines Inc. in the third quarter of 2021, for which there were no similar costs in 2022. Additionally, clinical trial and related costs decreased primarily due to the prioritization of the Company’s core programs in its clinical pipeline and the timing of the purchases of comparator drug used in clinical trials.
SG&A expense: SG&A expense for the third quarter of 2022 were $34.6 million, compared to $35.1 million for the third quarter of 2021.
Interest expense: Interest expense for the third quarter of 2022 was $6.1 million, compared to $8.0 million for the third quarter of 2021.
Net loss: Karyopharm reported a net loss of $36.3 million, or $0.45 per share, for the third quarter of 2022, compared to a net loss of $51.8 million, or $0.69 per share, for the third quarter of 2021. Net loss included non-cash stock-based compensation expense of $6.8 million and $7.4 million for the third quarters ended September 30, 2022 and 2021, respectively.
Cash position: Cash, cash equivalents, restricted cash and investments as of September 30, 2022, totaled $150.1 million, compared to $235.6 million as of December 31, 2021.
Non-GAAP Financial Information
Karyopharm uses a non-GAAP financial measure, non-GAAP 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, November 3, 2022, at 4:30 p.m. Eastern Time, to discuss the third 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 various indications in a growing number of ex-U.S. territories and countries, including but not limited to the European Union, the United Kingdom, China, South Korea, Canada, Israel and Taiwan. XPOVIO and NEXPOVIO is marketed by Karyopharm’s partners, Antengene, Menarini, Neopharm and FORUS in China, South Korea, Singapore, Australia, Hong Kong, Germany, Austria, Israel and Canada.
Please refer to the local Prescribing Information for full details.
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]
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.