On February 29, 2024 PMV Pharmaceuticals, Inc. (Nasdaq: PMVP), a precision oncology company pioneering the discovery and development of small molecule, tumor-agnostic therapies targeting p53, reported financial results for the fourth quarter and full year ended December 31, 2023, and provided a corporate update (Press release, PMV Pharma, FEB 29, 2024, View Source [SID1234640659]).

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"PMV continues to make significant progress with rezatapopt, a first-in-class precision oncology investigational therapy in patients with advanced solid tumors with a p53 Y220C mutation," said David Mack, Ph.D., President and Chief Executive Officer of PMV Pharma. "Our registrational, tumor-agnostic Phase 2 clinical trial remains on track to initiate in the first quarter of this year."

Dr. Mack added, "We have extended our cash runway to the end of 2026 by prioritizing the development of rezatapopt and refocusing our discovery research efforts. We look forward to advancing the rezatapopt clinical program to bring a much-needed new treatment option to patients."

Full Year 2023 and Recent Corporate Highlights:

•
Charles Baum, M.D., Ph.D., former Mirati Chief Executive Officer, appointed to serve as senior clinical advisor.

•
Phase 1 analysis from the PYNNACLE Phase 1/2 study of rezatapopt in a subgroup of patients with advanced ovarian cancer harboring a TP53 Y220C mutation selected as a late-breaking oral presentation at the 2024 SGO Annual Meeting on Women’s Cancer. The data will be presented on March 18, 2024 during the Scientific Plenary V Late-Breaking Abstract Session 2, from 2:30 PM – 3:45 PM PT.

•
Prioritization of rezatapopt development and focused discovery research efforts resulted in a workforce reduction; cost savings expected to extend cash runway to end of 2026.

•
Updated data from Phase 1 PYNNACLE clinical trial presented at the 2023 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) demonstrated responses across multiple tumor types with a median duration of response of seven months and a confirmed overall response rate of 38% at the Recommended Phase 2 dose (RP2D) of
2000 mg daily for the intended Phase 2 population of TP53 Y220C and KRAS wild-type patients.

•
Concluded successful End-of-Phase 1 U.S. Food and Drug Administration (FDA) meeting with alignment on RP2D and key elements of single arm, tumor agnostic Phase 2 registrational portion of PYNNACLE study.

•
Deepika Jalota, Pharm.D., Chief Development Officer, and Marc Fellous, M.D., Senior Vice President, Head of Clinical Development and Medical Affairs appointed to lead the rezatapopt clinical program.

•
Promoted Michael Carulli to Chief Financial Officer and appointed Masha Poyurovsky, Ph.D., as Vice President of Biology.

•
Initiated enrollment in the combination arm of the PYNNACLE study with rezatapopt and KEYTRUDA (pembrolizumab).

Fiscal Year 2023 Financial Results

•
As of December 31, 2023, PMV Pharma had $228.6 million in cash, cash equivalents, and marketable securities, compared to $243.5 million at December 31, 2022. Net cash used in operations was $55.7 million for the year ended December 31, 2023, compared to $63.8 million for the year ended December 31, 2022.

•
Net loss for the year ended December 31, 2023, was $69.0 million compared to $73.3 million for the year ended December 31, 2022.

•
Research and development (R&D) expenses were $55.9 million for the year ended December 31, 2023, compared to $52.0 million for the year ended December 31, 2022. The increase in R&D expenses was primarily related to increased headcount and clinical expenses for advancing rezatapopt, the Company’s lead drug candidate.

•
General and administrative (G&A) expenses were $24.2 million for the year ended December 31, 2023, compared to $25.1 million for the year ended December 31, 2022. The decrease in G&A expenses was primarily due to facility-related costs now allocated to research as our new laboratory building in Princeton, NJ began operations.

KEYTRUDA (pembrolizumab) is a registered trademark of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About Rezatapopt

Rezatapopt (PC14586) is a first-in-class, small molecule, p53 reactivator designed to selectively bind to the pocket in the p53 Y220C mutant protein, restoring the wild-type, or normal, p53 protein structure and tumor-suppressing function. The U.S. Food and Drug Administration (FDA) granted Fast Track designation to rezatapopt for the treatment of patients with locally advanced or metastatic solid tumors with a p53 Y220C mutation.

On February 29, 2024 Pacira BioSciences, Inc. (Nasdaq: PCRX), the industry leader in its commitment to non-opioid pain management and regenerative health solutions, reported financial results for the fourth quarter and full-year of 2023 (Press release, Pacira Pharmaceuticals, FEB 29, 2024, View Source;991.htm [SID1234640658]).

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"Now that I have spent several weeks working with the Pacira team, I am even more enthusiastic to lead this great company as we build upon an impressive foundation of success," said Frank D. Lee, chief executive officer of Pacira BioSciences. "Looking ahead, we are sharply focused on driving long-term growth, furthering our patient centric culture and establishing high standards for operational excellence. Throughout 2024, we plan to advance the launch of EXPAREL in two key lower extremity nerve blocks and prepare for the significant catalyst ahead in NOPAIN. In parallel, we are taking the necessary steps to reallocate our efforts and resources to ensure the organization is best positioned for sustainable success.
We have the people, the purpose, and the products to change the course of pain management and, hopefully, to help save patients from the deadly effects of opioid addiction."
2023 Fourth Quarter and Full-Year Financial Highlights
•Fourth quarter revenues of $181.2 million and full-year revenues of $675.0 million.
•Fourth quarter GAAP net income of $24.9 million or $0.54 per basic share and $0.50 per diluted share and full-year GAAP net income of $42.0 million or $0.91 per basic share and $0.89 per diluted share.
•Fourth quarter adjusted EBITDA of $65.4 million and full-year adjusted EBITDA of $214.5 million.
See "Non-GAAP Financial Information" below.
Recent Business Highlights
•FDA Approval of New EXPAREL 200-liter Manufacturing Suite. In February 2024, the U.S. Food and Drug Administration (FDA) approved the company’s supplemental New Drug Application (sNDA) for its 200-liter EXPAREL manufacturing suite in San Diego, CA. The company expects to start selling commercial product manufactured at this 200-liter suite later this year, which will help drive a more favorable mix of commercial product sold and benefit EXPAREL gross margins over time.
•Frank D. Lee Appointed as Chief Executive Officer. In December 2023, the company’s Board of Directors appointed Frank D. Lee as chief executive officer and a member of the Board, effective January 2, 2024. Mr. Lee brings more than three decades of global experience and a strong track

record of product development and commercial leadership success across a wide range of therapeutic areas within the biotech and pharmaceutical industry. Most recently he served as chief executive officer and member of the board of directors of Forma Therapeutics from March 2019 through its acquisition by Novo Nordisk in October 2022. During his tenure at Forma, Mr. Lee transformed the company from an early-stage drug discovery company into one focused on the clinical development of lead assets in rare hematologic disorders and cancer. Prior to Forma, Mr. Lee spent 13 years at Genentech, a member of the Roche Group, in a series of leadership positions of increasing scope and responsibility for delivering transformative medicines to patients.
•FDA Approval of Expanded EXPAREL Label to Include Two Additional Nerve Block Indications. In November 2023, the FDA approved the company’s sNDA to expand the EXPAREL label to include administration in adults as an adductor canal block and a sciatic nerve block in the popliteal fossa. The approval is supported by a Phase 3 program data supporting EXPAREL as the first and only single-dose product to safely demonstrate four days of superiority versus bupivacaine. EXPAREL achieved statistical significance in postsurgical pain, opioid consumption and percentage of opioid-free patients (P<0.01).
•Two New EXPAREL Patents. In November 2023, the United States Patent and Trademark Office issued Patent Nos. 11,819,574 and 11,819,575, claiming composition of EXPAREL prepared by an enhanced manufacturing process and composition of matter for EXPAREL, respectively. Each of these EXPAREL patents are listed in the FDA’s "Approved Drug Products with Therapeutic Equivalence Evaluations" (the "Orange Book"). These two patents are among the ten Orange Book listed patents that are now listed for EXPAREL, all with an expiration date of January 22, 2041.
Fourth Quarter 2023 Financial Results
•Total revenues were $181.2 million in the fourth quarter of 2023, a 5% increase over the $172.0 million reported for the fourth quarter of 2022.
•EXPAREL net product sales were $143.9 million in the fourth quarter of 2023, a 4% increase over the $138.0 million reported for the fourth quarter of 2022.
•ZILRETTA net product sales were $28.7 million in the fourth quarter of 2023, a 3% increase over the $28.0 million reported for the fourth quarter of 2022.
•Fourth quarter 2023 iovera° net product sales were $6.0 million, a 32% increase over the $4.6 million reported in the fourth quarter of 2022.
•Sales of bupivacaine liposome injectable suspension to third-party licensees were $1.1 million in the fourth quarter of 2023, versus the $1.0 million reported for the fourth quarter of 2022.
•Total operating expenses were $148.1 million in the fourth quarter of 2023, versus the $181.8 million reported for the fourth quarter of 2022. Included in operating expenses in 2022 was a $26.1 million impairment of acquired in-process research and development (IPR&D).
•Research and development (R&D) expenses were $19.5 million in the fourth quarter of 2023, compared to $17.5 million in the fourth quarter of 2022. The company’s R&D expenses included $6.9 million and $7.3 million of product development and manufacturing capacity expansion costs in the fourth quarters of 2023 and 2022, respectively.
•Selling, general and administrative (SG&A) expenses were $65.8 million in the fourth quarter of 2023, compared to $64.0 million in the fourth quarter of 2022.

•GAAP net income was $24.9 million, or $0.54 per basic share and $0.50 per diluted share in the fourth quarter of 2023, compared to a GAAP net loss of $10.1 million, or $0.22 per basic and diluted share in the fourth quarter of 2022.
•Non-GAAP net income was $45.1 million, or $0.97 per basic share and $0.89 per diluted share in the fourth quarter of 2023, compared to $37.0 million, or $0.81 per basic share and $0.73 per diluted share in the fourth quarter of 2022.
•Adjusted EBITDA was $65.4 million in the fourth quarter of 2023, a 11% increase compared to $58.8 million in the fourth quarter of 2022.
•Pacira ended the fourth quarter of 2023 with cash, cash equivalents and available-for-sale investments ("cash") of $281.0 million. Cash provided by operations was $47.6 million in the fourth quarter of 2023, compared to $42.0 million in the fourth quarter of 2022.
•Pacira had 46.4 million basic and 52.1 million diluted weighted average shares of common stock outstanding in the fourth quarter of 2023.
•For non-GAAP measures, Pacira had 52.1 million and 51.9 million diluted weighted average shares of common stock outstanding in the fourth quarter of 2023 and 2022, respectively.
See "Non-GAAP Financial Information" below.
Full-Year 2023 Financial Results
•Total revenues were $675.0 million in 2023, a 1% increase over the $666.8 million reported in 2022.
•EXPAREL net product sales were $538.1 million in 2023, a nominal increase compared to the $536.9 million reported in 2022. There were two less selling days in 2023 compared to 2022.
•ZILRETTA net product sales were $111.1 million in 2023, a 5% increase over the $105.5 million reported in 2022.
•Full-year iovera° net product sales were $19.7 million, a 29% increase over the $15.3 million reported in 2022.
•Full-year sales of bupivacaine liposome injectable suspension to third-party licensees were $3.3 million in 2023, versus the $6.5 million reported in 2022.
•Total operating expenses were $587.3 million in 2023, compared to $606.8 million in 2022.
•R&D expenses were $76.3 million in 2023, compared to $84.8 million in 2022. The company’s R&D expenses include $33.4 million and $24.6 million of product development and manufacturing capacity expansion costs in 2023 and 2022, respectively.
•SG&A expenses were $269.4 million in 2023, compared to $254.5 million in 2022.
•GAAP net income was $42.0 million, or $0.91 per basic share and $0.89 per diluted share in 2023, compared to $15.9 million, or $0.35 per basic share and $0.34 per diluted share in 2022.
•Non-GAAP net income was $142.0 million, or $3.07 per basic share and $2.81 per diluted share in 2023, compared to $120.7 million, or $2.65 per basic share and $2.39 per diluted share in 2022.
•Adjusted EBITDA was $214.5 million in 2023, a 1% increase over $212.7 million in 2022.
•Cash provided by operations was $154.6 million in 2023, compared to $145.3 million in 2022.
•Pacira had 46.2 million basic and 52.0 million diluted weighted average shares of common stock outstanding in 2023.

•For non-GAAP measures, Pacira had 52.0 million and 52.7 million diluted weighted average shares of common stock outstanding in 2023 and 2022, respectively.
See "Non-GAAP Financial Information" below.
2024 Financial Guidance
Today the company is providing full-year 2024 financial guidance as follows:
•Total revenue of $680 million to $705 million;
•Non-GAAP gross margin of 74% to 76%;
•Non-GAAP R&D expense of $70 million to $80 million;
•Non-GAAP SG&A expense of $245 million to $265 million; and
•Stock-based compensation of $50 million to $55 million.
See "Non-GAAP Financial Information" below.
Today’s Conference Call and Webcast Reminder
The Pacira management team will host a conference call to discuss the company’s financial results and recent developments today, Thursday, February 29, 2024, at 8:30 a.m. ET. For listeners who wish to participate in the question-and-answer session via telephone, please pre-register at investor.pacira.com/upcoming-events. All registrants will receive dial-in information and a PIN allowing them to access the live call. In addition, a live audio of the conference call will be available as a webcast. Interested parties can access the event through the "Events" page on the Pacira website at investor.pacira.com.

Non-GAAP Financial Information
This press release contains financial measures that do not comply with U.S. generally accepted accounting principles (GAAP), such as non-GAAP gross margin, non-GAAP cost of goods sold, non-GAAP research and development (R&D) expense, non-GAAP selling, general and administrative (SG&A) expense, non-GAAP net income, non-GAAP net income per common share, non-GAAP weighted average diluted common shares outstanding, EBITDA (earnings before interest, taxes, depreciation and amortization) and adjusted EBITDA, because these non-GAAP financial measures exclude the impact of items that management believes affect comparability or underlying business trends.

These measures supplement the company’s financial results prepared in accordance with GAAP. Pacira management uses these measures to better analyze its financial results, estimate its future cost of goods sold, R&D expense and SG&A expense outlook for 2024 and to help make managerial decisions. In management’s opinion, these non-GAAP measures are useful to investors and other users of the company’s financial statements by providing greater transparency into the ongoing operating performance of Pacira and its future outlook. Such measures should not be deemed to be an alternative to GAAP requirements or a measure of liquidity for Pacira. The non-GAAP measures presented here are also unlikely to be comparable with non-GAAP disclosures released by other companies. See the tables below for a reconciliation of GAAP to non-GAAP measures.

On February 29, 2024 Laminar Pharmaceuticals S.A., a clinical-stage biotechnological company developing novel therapies to treat diverse pathologies with unmet clinical needs, reported that the Independent Data Monitoring Committee (IDMC) after evaluating the interim clinical results of the CLINGLIO clinical trial, has recommended that the trial should "continue without modifications" (Press release, Laminar Pharma, FEB 29, 2024, View Source [SID1234640657]). The CLINGLIO study is a multinational, phase 2b/3, randomized, double-blind clinical trial evaluating LAM561 in combination with standard-of-care (SoC; combined tumour resection and chemoradiotherapy) for newly diagnosed glioblastoma (GBM) patients. The CLINGLIO trial, funded by a European Commission Grant (H2020) is being carried out in 21 hospitals in Spain, Italy, France, and UK. The investigational study drug, LAM561 (idroxioleic acid, sodium; 2-OHOA) is a synthetic fatty acid with a novel therapeutic approach, administrated orally to treat this devastating type of cancer.

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As part of the pre-specified plan, the experts from the IDMC committee at their meeting on February 23 recommended, based upon their evaluation of the unblinded medical and clinical statistical data from 103 patients, that the CLINGLIO trial should continue without modification. This interim analysis was conducted following the committee’s assessment of the efficacy – survival without progression (tumor growth or clinical deterioration) – of LAM561 after 45 progression events have occurred. This recommendation was eagerly awaited by Laminar as it ensures that the trial remains on track to have its first open readout at 66 progressions, expected in the Summer of 2024. Moreover, this interim recommendation by the IDMC confirms that with the current level of evidence, futility (lack of clinical benefit of the drug) has not been identified and continuance of the study is recommended.

"The positive IDMC interim review of LAM561 efficacy in newly diagnosed GBM represents a leap forward for our most advanced development. This is the first time that the efficacy of LAM561 has been assessed against placebo, a huge milestone in the project, and this recommendation was the best possible outcome at this stage" said Dr Pablo Escribá, Chief Executive Officer of Laminar Pharmaceuticals. "With the IDMC’s recommendation, we will continue to advance the CLINGLIO study to confirm the potential of LAM561 to improve the prognosis and quality of life in first-line glioblastoma patients treated with standard-of-care."

From Laminar’s point of view, this positive and expected recommendation follows the encouraging results from previous IDMC meeting, focused on safety, held in September 2023, in which no concerns were raised based on evaluation of the available safety data. Subsequent ongoing follow-up and monitoring of medical and pharmacovigilance data have not raised any further safety concerns to the medical team and study monitor nor the trial’s Ethics Board. Oral LAM561 has been well tolerated and indicates a safety profile consistent with prior clinical trials.

"A leap forward, and also the beginning of the last step to potentially reach clinical practice, as the next planned interim analysis will provide the unblinded clinical benefit/risk ratio data needed for the request for Conditional Market Authorization." – added Dr Adrian G. McNicholl, Laminar’s Chief of Clinical Operations. "However, even though we are hopeful with the advancement of the LAM561 clinical program, we must be careful not to raise patient’s expectations, as this is an investigational medicinal product, and we need to wait until the outcome of the next interim analysis has been re-evaluated by the IDMC and has been assessed by the regulatory agencies with whom we are already in direct contact".

As a designated orphan medicinal product in the EU, the study protocol, scientific validity, methodology, analyses and endpoints have been discussed in detail with the EMA during successive requests for Protocol Assistance. The CLINGLIO trial is considered pivotal in that results showing significant clinical benefit could be sufficient for a request for conditional marketing authorization in the EU late this year; and potential full marketing authorization in 2025, for which enabling pre-submission interactions with the EMA have been initiated.

On February 29, 2024 Kineta, Inc. (Nasdaq: KA), a clinical-stage biotechnology company focused on the development of novel immunotherapies in oncology that address cancer immune resistance, reported that it has completed a review of its business, including the status of its programs, resources and capabilities (Press release, Kineta, FEB 29, 2024, View Source;utm_medium=rss&utm_campaign=kineta-announces-restructuring-and-exploration-of-strategic-alternatives [SID1234640656]). Following this review, Kineta is implementing a significant corporate restructuring to substantially reduce expenses and preserve cash. The restructuring includes a significant workforce reduction and the termination of enrollment of new patients in its ongoing VISTA-101 Phase 1/2 clinical trial evaluating KVA12123 in patients with advanced solid tumors. Patients currently enrolled in the trial will be permitted to continue to participate. The company has made this decision, in part, because certain investors have indicated they will not fulfill their funding obligations pursuant the previously disclosed second tranche of the company’s contemplated private placement later this year.

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The company will conduct a comprehensive exploration of strategic alternatives focused on maximizing shareholder value including potential sale of assets of the company, a sale of the company, licensing of assets, a merger, liquidation or other strategic action. There can be no assurance that the exploration of strategic alternatives will result in any agreements or transactions, or that, if completed, any agreements or transactions will be successful or on attractive terms. The company does not expect to disclose or provide an update concerning developments related to this process until the company enters into definitive agreements or arrangements with respect to a transaction or otherwise determines that other disclosure is necessary or appropriate.

Kineta is reducing its workforce by approximately 64%, which will result in the elimination of seven positions. This includes Kineta’s Chief Executive Officer, Shawn Iadonato, Ph.D., who will continue to serve on the company’s Board of Directors, and Kineta’s General Counsel and Secretary, Pauline Kenny. Each of Dr. Iadonato and Ms. Kenny will continue to support the company in a consulting capacity until December 31, 2024.

"We continue to believe in the promise of KVA12123 and are enthusiastic about the trial data that has been collected to date," said Shawn Iadonato, Kineta CEO. "We are deeply disappointed that certain investors in the April financing will not fulfill their funding obligations."

On February 29, 2024 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported financial results for the fourth quarter and full year ended December 31, 2023 (Press release, Karyopharm, FEB 29, 2024, View Source [SID1234640655]). In addition, Karyopharm highlighted select corporate milestones and provided an overview of its key clinical development programs.

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"We made significant progress in 2023 across our clinical pipeline and continued to build on our foundation in the highly competitive multiple myeloma space. The encouraging clinical results that we presented last year reinforce the potential of our three ongoing pivotal Phase 3 trials in addressing critical unmet needs of cancer patients," said Richard Paulson, President and Chief Executive Officer of Karyopharm. "Our drive for innovation and progress will continue into 2024, by focusing our resources to advance our Phase 3 trials. We are enthusiastic about the upcoming top-line read-outs from these trials and what they could mean for patients and selinexor’s growth potential."

Fourth Quarter 2023 and Recent Highlights

Research and Development (R&D) Highlights

Long-term exploratory analysis of the pre-specified subgroup of patients with advanced or recurrent TP53 wild-type endometrial cancer (EC) from the Phase 3 SIENDO trial (NCT03555422) was presented at the International Gynecological Cancer Society Annual Global Meeting in Seoul, South Korea, with updated progression-free survival (PFS). As of the September 1, 2023 data cut-off date, median PFS was 27.4 months in the selinexor treatment arm (n=77) as compared to 5.2 months (n=36) in the placebo arm. Immature overall survival data showed an encouraging signal and corroborated the PFS results.

Oral presentation at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) 2023 Annual Meeting of the updated results from the Phase 1 trial (XPORT-MF-034) evaluating selinexor in combination with ruxolitinib in patients with treatment-naïve myelofibrosis (MF) showed encouraging long-term durability. 79% of intent-to-treat (ITT) patients (11 out of 14) treated with 60mg selinexor achieved ≥35% reduction in spleen volume (SVR35) at week 24, and continued to remain in radiographic response as of the August 1, 2023 data cut-off date. In addition, 58% of the ITT patients (7 out of 12) who achieved symptom improvement of ≥ 50% (TSS50) at week 24 also remained in response as of the data cut-off. In general, early cytokine reduction at week 4 was associated with spleen volume reduction at week 24, was sustained until the end of treatment, and is a potential sign of disease modification.

Clinical trial collaboration agreement executed with Bristol Myers Squibb (BMS) to evaluate selinexor in combination with BMS’ proprietary investigational cereblon E3 ligase modulator (CELMoD) agent mezigdomide in patients with relapsed/refractory multiple myeloma (MM) progressing after T-cell immunotherapies, potentially adding to the growing body of evidence that selinexor has the potential to show meaningful benefit in combination with MM therapies with differing mechanisms of action; the study of selinexor/mezigdomide enables further evaluation of selinexor’s role in maintaining an optimal T-cell environment.
XPOVIO Commercial Performance

Achieved U.S. net product revenue for the year ended December 31, 2023 of $112 million, compared to $120 million for the year ended December 31, 2022. U.S. net product revenue for the fourth quarter of 2023 was $25 million, compared to $31 million for the fourth quarter of 2022. Although demand for XPOVIO continued its growth in the community setting in 2023, it was adversely impacted in the academic setting due to increased competition in the later-lines.

Continued progress in shifting selinexor use into earlier lines of therapy, with patient mix approaching 70% in the second to fourth lines in 2023 versus 55% in 20221.

XPOVIO net product revenue was adversely impacted year-over-year by increased utilization of the KaryForward Patient Assistance Program (PAP), due to MM foundation closures2, contributing to ~10% of total demand in 2023 as compared to ~5% in 2022, leading to an estimated impact of ~$6 million. Additionally, increased competition and higher gross-to-net, driven by increased 340B discounts and Medicaid rebates during the year, adversely impacted XPOVIO net product revenue in 2023.
Intellectual Property

The U.S. Patent and Trademark Office issued patents directed toward the polymorphic form of selinexor present in XPOVIO, pharmaceutical compositions comprising the polymorphic form and methods of treatment using the polymorphic form and the pharmaceutical compositions. The newly issued patents will expire in August 2035.
Anticipated Catalysts and Operational Objectives in 2024 and 2025

Present updated exploratory subgroup analysis results in patients with TP53 wild-type EC from the Phase 3 SIENDO trial in 2024.

Complete enrollment in pivotal XPORT-EC-042 Phase 3 trial in TP53 wild-type EC in 2H 2024 and report top-line results in 1H 2025.

Report updated results from the Phase 1 trial of selinexor in combination with ruxolitinib in patients with treatment-naïve MF in 2024.

Report preliminary results from the Phase 2 trial evaluating the efficacy and safety of selinexor monotherapy in subjects with JAK inhibitor-naïve MF and moderate thrombocytopenia in 2H 2024.

Report top-line results from pivotal Phase 3 trial of selinexor in combination with ruxolitinib in treatment-naïve MF in 2H 2025.

Publish and present efficacy and safety data on selinexor 40mg in combination with pomalidomide and dexamethasone from ongoing STOMP/028 Phase 2 trials in patients with MM in 2024.

Report additional data on selinexor’s impact on T-cell fitness and potential combinability with multiple agents pre- or post-T-cell therapy in patients with MM in 2024.

Complete enrollment in pivotal Phase 3 trial evaluating an oral combination of 40mg selinexor, pomalidomide and dexamethasone in patients with previously treated MM in 2H 2024 and report top-line results in 1H 2025.

Maintain the Company’s commercial foundation in the competitive MM marketplace, driving increased XPOVIO revenues.

Continue global launches and reimbursement approvals for selinexor by partners in ex-U.S. territories.
2024 Financial Outlook

Based on its current operating plans, Karyopharm expects the following for full year 2024:

Total revenue to be in the range of $140 million to $160 million. Total revenue consists of U.S. XPOVIO net product revenue and license, royalty and milestone revenue earned from partners.

U.S. XPOVIO net product revenue to be in the range of $100 million to $120 million.

R&D and SG&A expenses to be in the range of $260 million to $280 million, which includes approximately $20 million to $25 million of estimated non-cash stock-based compensation expense.

The Company expects that its existing cash, cash equivalents and investments, and the revenue it expects to generate from XPOVIO net product sales, as well as revenue generated from its license agreements, will be sufficient to fund its planned operations into late 2025.
Full Year and Fourth Quarter 2023 Financial Results

Total revenue: Total revenue for the fourth quarter of 2023 was $33.7 million, compared to $33.6 million for the fourth quarter of 2022. Total revenue for the year ended December 31, 2023 was $146.0 million, compared to $157.1 million for the year ended December 31, 2022.

Net product revenue: Net product revenue for the fourth quarter of 2023 was $25.1 million, compared to $31.1 million for the fourth quarter of 2022. Net product revenue for the year ended December 31, 2023 was $112.0 million, compared to $120.4 million for the year ended December 31, 2022.

License and other revenue: License and other revenue for the fourth quarter of 2023 was $8.7 million, compared to $2.5 million for the fourth quarter of 2022. License and other revenue for the year ended December 31, 2023 was $34.0 million, compared to $36.6 million for the year ended December 31, 2022.

Cost of sales: Cost of sales for the fourth quarter of 2023 was $1.5 million, compared to $1.9 million for the fourth quarter of 2022. Cost of sales for the year ended December 31, 2023 was $4.9 million, compared to $5.2 million for the year ended December 31, 2022. Cost of sales reflects the costs of XPOVIO units sold and third-party royalties on net product revenue.

R&D expenses: R&D expenses for the fourth quarter of 2023 were $39.4 million, compared to $30.9 million for the fourth quarter of 2022. R&D expenses for the year ended December 31, 2023 were $138.8 million, compared to $148.7 million for the year ended December 31, 2022. The decrease in R&D expenses in 2023 compared to 2022 was primarily due to a decrease in personnel costs and stock-based compensation attributable to a reduction in headcount and contractors, including severance-related expenses incurred in 2022. These decreases were partially offset by an increase in clinical trial and related costs primarily due to the advancement of the Company’s three pivotal Phase 3 trials and the timing of purchases of comparator drug used in the Company’s clinical trials.

SG&A expenses: SG&A expenses for the fourth quarter of 2023 were $30.7 million, compared to $34.6 million for the fourth quarter of 2022. SG&A expenses for the year ended December 31, 2023 were $131.9 million, compared to $145.4 million for the year ended December 31, 2022. The decrease in SG&A expenses in 2023 compared to 2022 was primarily due to a decrease in stock-based compensation because of severance-related expenses incurred in 2022.

Interest expense: Interest expense for the fourth quarter of 2023 was $6.2 million, compared to $5.9 million for the fourth quarter of 2022. Interest expense for the year ended December 31, 2023 was $23.8 million, compared to $25.0 million for the year ended December 31, 2022.

Net loss: Karyopharm reported a net loss of $41.8 million, or $0.36 per basic and diluted share, for the fourth quarter of 2023, compared to a net loss of $38.5 million, or $0.43 per basic and diluted share, for the fourth quarter of 2022. Net loss includes non-cash stock-based compensation expense of $5.2 million and $6.2 million for the fourth quarters of 2023 and 2022, respectively. Karyopharm reported a net loss of $143.1 million, or $1.25 per basic and diluted share, for the year ended December 31, 2023, compared to a net loss of $165.3 million, or $2.02 per basic and diluted share, for the year ended December 31, 2022. Net loss includes non-cash stock-based compensation expense of $21.7 million and $35.4 million for the years ended December 31, 2023 and 2022, respectively.

Cash position: Cash, cash equivalents, restricted cash and investments as of December 31, 2023 totaled $192.4 million, compared to $279.7 million as of December 31, 2022.

Conference Call Information

Karyopharm will host a conference call today, February 29, 2024, at 8:00 a.m. Eastern Time, to discuss the fourth quarter and full year 2023 financial results and the financial outlook for 2024 and to provide other business updates. To access the conference call, please dial (800) 836-8184 (local) or (646) 357-8785 (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. 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, South Korea, Israel, Singapore, Hong Kong, Mainland China, Australia, Canada, Taiwan and Macau 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 two 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.
Use In Specific Populations
Lactation: Advise not to breastfeed.

For additional product information, including full prescribing information, please visit www.XPOVIO.com.

To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1‐888‐209‐9326 or FDA at 1‐800‐FDA‐1088 or www.fda.gov/medwatch.