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MacroGenics Provides Update on Corporate Progress and Third Quarter 2023 Financial Results

On November 6, 2023 MacroGenics, Inc. (NASDAQ: MGNX), a biopharmaceutical company focused on developing, manufacturing and commercializing innovative antibody-based therapeutics for the treatment of cancer, reported an update on its recent corporate progress and reported financial results for the quarter ended September 30, 2023 (Press release, MacroGenics, NOV 6, 2023, View Source [SID1234637037]).

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"Since mid-2022, we have received $335 million in non-dilutive capital from our collaboration partners and reduced our quarterly cash burn, enabling us to extend our cash runway into 2026. Over the next two years, we anticipate having multiple data read-outs, the first of which we expect during the first half of 2024 related to the now fully-enrolled TAMARACK study of vobra duo in metastatic castration-resistant prostate cancer," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "During this two-year period, we also expect data from the LORIKEET Phase 2 study of lorigerlimab in prostate cancer, results from the dose escalation study of MGD024 and results from a planned vobra duo plus lorigerlimab dose expansion cohort. Also during this time, we anticipate advancing multiple new ADC molecules from our preclinical portfolio, the first of which (MGC026) recently progressed to IND submission."

Updates on Proprietary Investigational Programs

Recent progress and anticipated events related to MacroGenics’ investigational product candidates are highlighted below.

Vobramitamab duocarmazine (vobra duo) is an antibody-drug conjugate (ADC) that targets B7-H3, an antigen with broad expression across multiple solid tumors and a member of the B7 family of molecules involved in immune regulation.
MacroGenics recently completed enrollment of the TAMARACK Phase 2 study of vobra duo ahead of schedule. This study is being conducted in patients with metastatic castration-resistant prostate cancer (mCRPC) who were previously treated with one prior androgen receptor axis-targeted therapy (ARAT). Participants may have received up to one prior taxane-containing regimen, but no other chemotherapy agents. The TAMARACK study is designed to evaluate vobra duo at two different doses, 2.0 mg/kg or 2.7 mg/kg every four weeks, across a total of approximately 100 patients. MacroGenics anticipates providing a clinical update in the first half of 2024.
MacroGenics continues to enroll a Phase 1/2 dose escalation study of vobra duo in combination with lorigerlimab in patients with various advanced solid tumors. The Company anticipates commencing a dose expansion study of this combination in 2024.
Lorigerlimab is a bispecific, tetravalent PD-1 × CTLA-4 DART molecule. MacroGenics commenced enrollment of LORIKEET, a randomized Phase 2 study of lorigerlimab in combination with docetaxel vs. docetaxel alone in second-line, chemotherapy-naïve mCRPC patients. A total of 150 patients are planned to be treated in the 2:1 randomized study. The current trial design includes a primary study endpoint of radiographic progression-free survival (rPFS).
MGD024 is a next-generation, humanized CD123 × CD3 DART molecule designed to minimize cytokine-release syndrome, while maintaining anti-tumor cytolytic activity, and permitting intermittent dosing through a longer half-life. MacroGenics continues to enroll patients in a Phase 1 dose-escalation study of MGD024 in patients with CD123-positive neoplasms, including acute myeloid leukemia and myelodysplastic syndromes.
MGC026 is an ADC with a topoisomerase inhibitor-based cytotoxic mechanism directed against an undisclosed solid tumor target. The Company recently submitted an investigational new drug (IND) application to the U.S. Food and Drug Administration and, assuming acceptance, anticipates commencing a Phase 1 dose escalation study beginning in the first quarter of 2024. More details on this program will be provided in early 2024.
Enoblituzumab is an Fc-optimized monoclonal antibody that targets B7-H3. MacroGenics’ academic collaborators plan to initiate the HEAT study, an investigator-sponsored, randomized Phase 2 clinical trial. This study is expected to commence enrollment in early 2024 and will evaluate the activity of neoadjuvant enoblituzumab given prior to radical prostatectomy in men with high-risk localized prostate cancer.
Other Corporate Updates

$15.7 Million Milestone Related to Gilead’s Nomination of a Bispecific Research Program. On September 5, 2023, MacroGenics announced that its partner, Gilead Sciences, Inc., nominated the first of two potential research programs, leveraging MacroGenics’ DART and TRIDENT platforms for generating bispecific antibodies. This nomination grants Gilead an exclusive option, upon achievement of a pre-defined preclinical milestone, to license worldwide rights to the research program. MacroGenics received $15.7 million related to this nomination subsequent to September 30, 2023.
Third Quarter 2023 Financial Results

Cash Position: Cash, cash equivalents and marketable securities balance as of September 30, 2023, was $256.4 million, compared to $154.3 million as of December 31, 2022. The Company’s cash balance as of September 30, 2023, did not include the $15.7 million milestone from Gilead subsequently received.
Revenue: Total revenue was $10.4 million for the quarter ended September 30, 2023, compared to total revenue of $41.7 million for the quarter ended September 30, 2022.
R&D Expenses: Research and development expenses were $30.1 million for the quarter ended September 30, 2023, compared to $48.2 million for the quarter ended September 30, 2022. The decrease was primarily related to decreased costs related to discontinued studies, partially offset by increased expenses related to preclinical ADC molecules and increased clinical expenses related to lorigerlimab.
SG&A Expenses: Selling, general and administrative expenses were $12.4 million for the quarter ended September 30, 2023, compared to $15.4 million for the quarter ended September 30, 2022. The decrease was primarily related to decreased selling costs for MARGENZA.
Other Income: During the quarter ended September 30, 2023, MacroGenics received a $50.0 million milestone payment from Sanofi S.A. related to the previously disclosed achievement of a primary endpoint in a TZIELD clinical study. The accounting treatment for this milestone is consistent with that for the $100.0 million proceeds received from the sale of the Company’s single-digit royalty interest on global net sales of TZIELD to DRI Healthcare Acquisitions LP in March 2023. Accordingly, $50.0 million was included in Other Income (as Gain on Royalty Monetization Arrangement) for the quarter ended September 30, 2023.
Net Income (Loss): Net income was $17.6 million for the quarter ended September 30, 2023, compared to net loss of $24.8 million for the quarter ended September 30, 2022.
Shares Outstanding: Shares of common stock outstanding as of September 30, 2023 were 62,028,904.
Cash Runway Guidance: MacroGenics anticipates that its cash, cash equivalents and marketable securities balance of $256.4 million as of September 30, 2023, plus the $15.7 million milestone subsequently received, in addition to projected and anticipated future payments from partners and product revenues should extend its cash runway into 2026. The Company’s expected funding requirements reflect anticipated expenditures related to the Phase 2 TAMARACK clinical trial, the Phase 2 LORIKEET study as well as MacroGenics’ other ongoing clinical and preclinical studies.

Conference Call Information

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The listen-only webcast of the conference call can be accessed under "Events & Presentations" in the Investor Relations section of MacroGenics’ website at View Source A recorded replay of the webcast will be available shortly after the conclusion of the call and archived on MacroGenics’ website for 30 days following the call.

November 6, 2023: MaaT Pharma Announces First Patient Dosed in Phase 2b Randomized Clinical Trial Evaluating MaaT033 in Patients Receiving Allo-HSCT

On November 6, 2023 MaaT Pharma (EURONEXT: MAAT – the "Company"), a clinical-stage biotech company and a leader in the development of Microbiome Ecosystem TherapiesTM (MET) dedicated to improving survival outcomes for patients with cancer, reported that the first patient has been treated as part of its Phase 2b trial, called PHOEBUS, investigating the efficacy of MaaT033 in improving overall survival (OS) at 12 months for patients with blood cancer receiving allo-HSCT (Press release, MaaT Pharma, NOV 6, 2023, View Source [SID1234637036]). The trial is an international, multi-center, randomized, double-blind, placebo-control study (NCT05762211), which will be conducted in up to 56 clinical investigation sites and is expected to enroll 387 patients. It is to date the largest randomized controlled trial assessing a microbiome therapy in oncology.

"Today marks a significant milestone for us as our second product, MaaT033, enters Phase 2b clinical trials in allo-HSCT. The opportunity to offer patients a capsule that can be taken at home not only furthers our overall mission to improve patient survival in multiple situations, but also reinforces our leadership in the field, as we believe this program is currently the most advanced in the microbiome/hemato-oncology field," said Hervé Affagard, CEO and co-founder of MaaT Pharma.

Prof. Florent Malard, Professor of Hematology at the Saint-Antoine Hospital and Sorbonne University, and principal investigator of the study added, "A growing body of evidence indicates that gut imbalance leads to higher mortality in our field. By directly targeting to restore the gut microbiome richness in patients receiving harsh and deleterious treatments, our goal is to ensure optimal microbiome functions that can potentially lead to improved hematopoietic and immune recovery as well as overall survival."

To date, the Company has received regulatory approvals from France and Germany, and the clinical trial will be expanded to sites in additional countries subject to regulatory approval.

Study objectives:

Primary endpoint: Overall Survival, evaluated in late 2026.
Secondary endpoints include evaluation of safety and tolerability before and after allo-HSCT, and evaluation of the engraftment of beneficial microbial species from MaaT033.
About MaaT033

MaaT033, a donor-derived, high-richness, high-diversity oral Microbiome Ecosystem TherapyTM containing anti-inflammatory ButycoreTM species, is currently being developed as an adjunctive therapy to improve overall survival in patients receiving HSCT and other cellular therapies. It aims to ensure optimal microbiota function and to address a larger patient population in a chronic setting. MaaT033 has been granted Orphan Drug Designation by the European Medicines Agency (EMA) in August 2023.

About Allogeneic hematopoietic stem cell transplantation (allo-HSCT)

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) for liquid tumors can replace cancerous cells, but the harsh conditioning treatments damage the gut microbiome, which has been linked to decreased survival, increased risk of graft-vs-host disease, and infections due to impaired immune function. Nearly 20,000 allo-HSCT transplantations per year in Europe were reported in 2021 by the European Society for Blood and Marrow Transplantation (EBMT) and continue to increase.

Kineta Unveils Positive New Data from VISTA-101 Clinical Trial of KVA12123 at the Society for Immunotherapy of Cancer’s (SITC) 38th Annual Meeting

On November 6, 2023 Kineta, Inc. (Nasdaq: KA), a clinical-stage biotechnology company focused on the development of novel immunotherapies in oncology that address cancer immune resistance, reported the presentation of new positive data from its ongoing VISTA-101 Phase 1/2 clinical trial evaluating KVA12123, the company’s VISTA blocking immunotherapy, in patients with advanced solid tumors at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 38th Annual Meeting (Press release, Kineta, NOV 6, 2023, View Source;utm_medium=rss&utm_campaign=kineta-unveils-positive-new-data-from-vista-101-clinical-trial-of-kva12123-at-the-society-for-immunotherapy-of-cancers-sitc-38th-annual-meeting [SID1234637035]). Thierry Guillaudeux, Ph.D., Chief Scientific Officer of Kineta, presented the company’s poster unveiling the new clinical data.

"We are excited to unveil these promising findings from our ongoing VISTA-101 clinical trial. VISTA blocking immunotherapy KVA12123 has performed remarkably well in demonstrating excellent safety and tolerability in the clinic. Notably, the pharmacokinetic data and biomarker assessments demonstrate the drug’s potential efficacy and confirm its mechanism of action," said Shawn Iadonato, Ph.D., Chief Executive Officer of Kineta. "We continue to advance KVA12123 to the higher monotherapy dose levels, as well as evaluate it in combination with pembrolizumab, where we recently announced the first patient dosed. Kineta is committed to advancing KVA12123 as a potential new immunotherapy for cancer patients in need of new treatment options."

The Phase 1/2 VISTA-101 trial (NCT05708950) enrolled 11 patients with advanced solid tumors in the first three monotherapy dose-escalation cohorts, where subjects received either 3, 10 or 30 mg of KVA12123 by intravenous (IV) infusion every two weeks. Primary objectives of the Phase 1/2 study are to evaluate the safety and tolerability of KVA12123 and to determine the recommended Phase 2 dose (RP2D). Patients enrolled in the study were heavily pretreated with multiple prior lines of therapy including chemotherapy, radiation and immunotherapy. Additional monotherapy and initial combination therapy data are anticipated in the second quarter of 2024.

Key highlights from the poster presentation:

Safety
Eleven patients were dosed and cleared the first three monotherapy cohorts. KVA12123 was well tolerated at all doses and no dose limiting toxicities (DLT) were observed. All KVA12123 treatment emergent adverse events were grades 1-2. Furthermore, no evidence of cytokine release syndrome (CRS) or associated cytokines including IL-6, TNFα & IL-10 were detected at any of the dose levels.

Pharmacokinetics and VISTA Receptor Occupancy (RO)
KVA12123 exhibited a greater than dose-proportional pharmacokinetic profile in drug exposure across all evaluated doses, consistent with target-mediated drug disposition at lower doses. To guide the RP2D decision, Kineta developed a proprietary assay to evaluate VISTA RO on immune cells from patients treated with KVA12123. KVA12123 achieved a greater than 90% VISTA RO at the 30 mg dose indicating that KVA12123 may be approaching an optimal clinical dose.

Biomarkers
KVA12123 demonstrated dose-proportional on-target biomarker immune responses involved in anti-tumor activity. KVA12123 demonstrated significant efficacy-related cytokine induction of CXCL10, MCP1, MIP1α and MIP1β, which are involved in immune cell activation and recruitment to the tumor microenvironment. Additionally, increases in anti-tumor immune cell subpopulations including nonclassical monocytes, NK cells, CD4+ T cells and CD8+ T cells were observed during treatment. Changes in these key biomarkers and immune cell populations are indicative of the anti-tumor effects of blocking VISTA.

The poster presentation is available for viewing under Publications in the KVA12123 section of the company’s website at www.kinetabio.com .

SITC Presentation Details:
Title: VISTA-101 – A phase 1/2 clinical trial of KVA12123, an engineered IgG1 targeting VISTA, alone and in combination with pembrolizumab in advanced solid tumors
Abstract Number: 780
Date / Time: Saturday, November 4 at 9:00 A.M. – 7:00 P.M. Pacific Time
Location: Exhibit Halls A and B1 – San Diego Convention Center

Kineta is advancing the VISTA-101 trial to higher monotherapy dose levels and recently initiated Part B of the study evaluating KVA12123 in combination with pembrolizumab. Additional monotherapy safety and efficacy data and combination therapy clinical data are anticipated in the second quarter of 2024.

Corporate presentation

On November 6, 2023 Keros therapeutics presented its corporate presentation (Presentation, Keros Therapeutics, NOV 6, 2023, View Source [SID1234637034]).

Karyopharm Announces New Preliminary Data in Overall Survival (OS) in Selinexor-Treated Patients with Advanced or Recurrent TP53 Wild-Type Endometrial Cancer as Part of Pre-Specified Exploratory Subgroup Analysis of the SIENDO Study

On November 6, 2023 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported the presentation of updated long-term safety and efficacy data from a pre-specified exploratory subgroup analysis of the SIENDO study (NCT03555422) in patients with advanced or recurrent TP53 wild-type endometrial cancer at the International Gynecological Cancer Society (IGCS) Annual Global Meeting in Seoul, South Korea (Press release, Karyopharm, NOV 6, 2023, View Source [SID1234637033]).

The primary analysis of the Phase 3 SIENDO study of selinexor maintenance therapy in advanced or recurrent endometrial cancer showed improvements in median progression-free survival (PFS) for the intent-to-treat (ITT) population but were not clinically meaningful. However, an exploratory analysis of a pre-specified subgroup of patients with TP53 wild-type endometrial cancer showed a promising efficacy signal.

In the exploratory subgroup analysis, 113 patients with wild-type endometrial cancer received selinexor (n=77) or placebo (n=36) as maintenance therapy. Although the survival data are immature, as of the September 1, 2023, data cut-off date, the study showed an encouraging OS signal in the TP53 wild-type population: hazard ratio 0.76 (95% Confidence Interval [CI]: 0.36-1.59), with median OS not reached in either arm after a median follow up of 28.9 months. Similarly, encouraging preliminary OS was observed in patients with TP53 wild-type/pMMR endometrial cancer: hazard ratio 0.57 (95% CI: 0.24-1.35), with median OS not reached in selinexor arm, and 35 months in placebo arm after median follow-up of 31.6 months , and a HR of 0.62 (95% CI: 0.06-6.81), with median OS not reached in either arm after median follow-up of 27.3 months in patients with TP53 wild-type/dMMR endometrial cancer.

"The preliminary OS data from this exploratory subset analysis of the SIENDO study corroborate the PFS results observed, which is compelling in this novel biomarker-driven population with high unmet need," said Reshma Rangwala, MD, PhD, Chief Medical Officer of Karyopharm. "These results showcase selinexor’s potential as a foundational treatment for patients with TP53 wild-type endometrial cancer. We look forward to additional data in the first half of 2025 from the company’s ongoing pivotal Phase 3 trial that may support U.S. and global regulatory filings."

No new safety signals were identified as of the last data cut-off date on September 1, 2023. The most common treatment-emergent adverse events (AEs) with selinexor treatment were nausea (90%), vomiting (60%), thrombocytopenia (42%) and diarrhea (42%), the majority of which were grades 1-2. Of note, the rate of nausea in the placebo patients was 34%, vomiting 11%, and diarrhea 37%. The most common reported grade 3-4 treatment-emergent AEs included neutropenia (18%), nausea (12%), and thrombocytopenia (10%). TEAEs leading to discontinuations in the selinexor group were reported in 16% of patients.

Currently, there are no specific targeted therapies available for patients with TP53 wild-type endometrial cancer. Advanced and recurrent endometrial cancer is associated with a poor prognosis, including limited disease control for patients who relapse after first-line systemic treatment.1 There are about 16,000 patients diagnosed with advanced and recurrent endometrial cancer in the U.S. each year2. More than 50% of these patients have TP53 wild-type cancer.2,3 TP53 wild-type is observed in both pMMR and dMMR populations. Recently there has been progress in potential treatment options in the dMMR subgroup with new targeted treatments; however, a large unmet need continues to exist for pMMR and for TP53 wild-type endometrial cancer.

"Given the unmet need that remains for patients whose disease is pMMR, I’m excited by the results demonstrating an encouraging, preliminary trend in OS, coupled with signals of improvement in disease progression," said Dr. Giovanni Scambia, oncology gynecologist at MITO and Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. "These results highlight the potential opportunity to further personalize therapies and provide a strong rationale to further evaluate selinexor as maintenance therapy in TP53 wild-type endometrial cancer in the ongoing Phase 3 trial".

IGCS Oral Presentation
Title: Selinexor maintenance for patients with TP53wt advanced or recurrent endometrial cancer: Long-term follow up of efficacy and safety subgroup analysis of the ENGOT-EN5/GOG-3055/SIENDO study
Presenter: Giovanni Scambia, MD, MITO and Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
Session Title: Plenary 02: Changing the Landscape of Endometrial Cancer
Date and Time: Sunday, November 5, 2023, 4:30pm – 5:30pm (GMT+9)/ 3:30am – 4:30am (ET)

IGCS Poster Presentation
Title: ENGOT-EN20/GOG-3083/XPORT-EC-042 A phase 3, randomized, placebo-controlled, double-blind, multicenter trial of selinexor in maintenance therapy for patients with P53 Wild-type, advanced or recurrent endometrial carcinoma
Presenter: Brian Slomovitz, MD, Mount Sinai Medical center and Florida International University
Date and Time: Sunday, November 5, 2023, through Tuesday, November 7, 2023

IGCS Industry Sponsored Symposium in Partnership with Gynecologic Oncology Group (GOG)
Title: The evolving landscape in molecular-driven investigational therapies for advanced endometrial cancer
Presenters: Bradley J. Monk, MD, US Cancer Associates; Domenica Lorusso, MD, PhD, Catholic University of Rome and Fondazione Policlinico Gemelli IRCCS; Ritu Salani, MD, MS, UCLA Medical Center
Date and Time: Monday, November 6, 2023, 7:15am – 8:15am (GMT+9)/ 6:15pm – 7:15pm (ET)

About the EC-042 Study
EC-042 (XPORT-EC-042; NCT05611931) is a global, Phase 3, randomized, double-blind study evaluating selinexor as a maintenance therapy following systemic therapy in patients with TP53 wild-type advanced or recurrent endometrial cancer. The EC-042 study was initiated in November 2022 and is expected to enroll up to 220 patients who will be randomized 1:1 to receive either a 60 mg, once-weekly, administration of oral selinexor or placebo until disease progression. The primary endpoint of the study is progression free survival (PFS), as assessed by an investigator, with overall survival as a key secondary endpoint. Further, in connection with the EC-042 Study, Karyopharm entered into a global collaboration with Foundation Medicine, Inc. to develop FoundationOneCDx, a tissue-based comprehensive genomic profiling test to identify and enroll patients whose tumors are TP53 wild-type.

About the SIENDO Study
Karyopharm’s evaluation of selinexor to treat patients with TP53 wild-type advanced or recurrent endometrial cancer is supported by data from an exploratory subgroup analysis from its ongoing SIENDO Study, a European Network of Gynaecological Oncological Trial Groups (ENGOT)-led trial in collaboration with the Gynecologic Oncology Group (GOG) Foundation, Inc. The SIENDO Study is a multicenter, randomized, double-blinded Phase 3 study evaluating the efficacy and safety of oral selinexor versus placebo as a front-line maintenance therapy in patients with advanced or recurrent endometrial cancer following at least one prior platinum-based combination chemotherapy treatment (NCT03555422). Participants in this study with advanced or recurrent disease who had a partial response or a complete response after at least 12 weeks of taxane-platinum combination chemotherapy were randomized in a 2:1 manner to receive either maintenance therapy of 80 mg of selinexor or placebo taken once per week, until disease progression. The primary endpoint in the study was PFS from time of randomization until death or disease progression as assessed by an investigator, with the goal of the study demonstrating a HR of 0.6. In the first quarter of 2022, Karyopharm presented top-line data from the SIENDO study, including preliminary exploratory subgroup analyses. Selinexor-treated patients had a median PFS of 5.7 months compared to 3.8 months for patients on placebo in the full trial population, which was not clinically meaningful. Patients in the exploratory subgroup of TP53 wild-type advanced or recurrent endometrial cancer treated with selinexor had a median PFS of 13.7 months compared to 3.7 months for the exploratory subgroup patients on placebo. There were no new safety signals identified, and a discontinuation rate of 10.5% due to adverse events (AEs). The most common treatment-emergent AEs in the SIENDO study of any grade were: nausea (84%), vomiting (52%), constipation (37%) and thrombocytopenia (37%). The most common grade 3 treatment-emergent AEs were nausea (10%), neutropenia (9%), thrombocytopenia (7%) and asthenia (6%).

About Endometrial Cancer
Endometrial cancer is the most common cancer of the female reproductive organs in the U.S., with approximately 66,000 new cases expected in 2023 leading to nearly 13,000 deaths.4 In 2020, there were approximately 130,000 new cases and 29,000 deaths in Europe from endometrial cancer, while on a global scale there were 417,000 new cases and approximately 97,000 deaths.5 Since 2002, the incidence of new cases and deaths from endometrial cancer have risen.6 Risk factors include obesity, Type 2 diabetes, high-fat diets, use of tamoxifen and oral estrogens, and delayed menopause.7 There are no approved therapies in the maintenance setting for patients with advanced or recurrent endometrial cancer.8

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.
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.