On July 25, 2023 RedHill Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company, reported that it has closed its previously announced registered direct offering for the purchase and sale of 1,301,923 of the Company’s American Depositary Shares ("ADSs") (or ADS equivalents), each ADS representing four hundred (400) ordinary shares, at a purchase price of $1.35 per ADS (or ADS equivalent) (Press release, RedHill Biopharma, JUL 25, 2023, View Source [SID1234633417]).

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The Company also announced the completion of the previously announced exercise of its existing Class A warrants exercisable for 1,500,000 ADSs, in the aggregate, at a reduced exercise price of $1.35 per ADS, in exchange for new warrants and the reduction in the exercise price of its existing Class B warrants as described below.

H.C. Wainwright & Co. acted as the exclusive placement agent for the transactions.

The gross proceeds to the Company from the transactions were approximately $3.8 million, before deducting the placement agent’s fees and other offering expenses payable by the Company. The Company intends to use the net proceeds from these transactions for general working capital, acquisitions, research and development, and general corporate purposes.

The securities described above other than the new warrants were offered by the Company and the ADSs issuable upon exercise of the Class A warrants are registered, pursuant to a "shelf" registration statement on Form F-3 (File No. 333-258259) previously filed with the Securities and Exchange Commission (the "SEC") on July 29, 2021, and declared effective by the SEC on August 9, 2021. The offering of the securities in the registered direct offering was made only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement. A final prospectus supplement and accompanying prospectus relating to the registered direct offering was filed with the SEC. Electronic copies of the final prospectus supplement and accompanying prospectus may be obtained on the SEC’s website at View Source or by contacting H.C. Wainwright & Co., LLC at 430 Park Avenue, 3rd Floor, New York, NY 10022, by phone at (212) 865-5711 or e-mail at [email protected].

In connection with the exercise of its Class A warrants, the exercising holder (i) received new warrants to purchase ADSs in a private placement and (ii) had the exercise price of its existing Class B warrants exercisable for 1,500,000 ADSs, in the aggregate, reduced to $1.80 per ADS. The new warrants are exercisable for up to an aggregate of 1,500,000 ADSs, at an exercise price of $1.80 per ADS and shall be exercisable until April 3, 2028. The new warrants described above were offered in a private placement under Section 4(a)(2) of the Securities Act of 1933, as amended (the "Act"), and Regulation D promulgated thereunder and, along with the ADSs representing ordinary shares underlying such warrants, have not been registered under the Act, or applicable state securities laws. Accordingly, the new warrants and the ADSs underlying the warrants may not be offered or sold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Act and such applicable state securities laws. As part of the transaction, the Company has agreed to file a resale registration statement on Form F-3 with the SEC within 15 days of the closing to register the resale of the ADSs underlying the new warrants issued in the private placement.

In connection with the registered direct offering, the Company also agreed that (i) certain existing warrants to purchase an aggregate of 330,106 ADSs at an exercise price of $4.75 per ADS and (ii) certain existing warrants to purchase an aggregate of 971,817 ADSs at an exercise price of $4.6305 per ADS, were amended to have a reduced exercise price of $1.80 per ADS.

This press release shall not constitute an offer to sell or a solicitation of an offer to buy any of the securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

On July 25, 2023 PDS Biotechnology Corporation (Nasdaq: PDSB), a clinical-stage immunotherapy company developing a growing pipeline of targeted cancer immunotherapies and infectious disease vaccines based on the Company’s proprietary T cell activating platforms, reported that an abstract detailing immune response data from the VERSATILE-002 Phase 2 clinical trial investigating PDS0101 in combination with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab), in patients with unresectable, recurrent or metastatic human papillomavirus (HPV)16-positive head and neck cancer has been accepted for presentation at the European Society for Medical Oncology Congress 2023 (ESMO Congress 2023) (Press release, PDS Biotechnology, JUL 25, 2023, View Source [SID1234633416]). ESMO (Free ESMO Whitepaper) Congress 2023 is being held October 20-24, 2023 in Madrid.

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The abstract, titled, "Polyfunctional HPV16-Specific T cell responses in subjects receiving PDS0101 and pembrolizumab combination treatment for recurrent/metastatic HPV16-positive head and neck squamous cell carcinoma (HNSCC)," reports on the ability of PDS0101 in combination with KEYTRUDA to induce the right type of HPV16-specific multifunctional T cell responses in the treatment of advanced HPV16-positive head and neck cancer. PDS0101 is designed to stimulate a potent targeted T cell attack against HPV16-positive cancers. The immunological clinical data demonstrates the immunotherapy’s potential to generate clinically-relevant multifunctional HPV16-targeted CD8 and CD4 T cells with minimal toxicity in advanced head and neck cancer patients.

"We are pleased to present biomarker data from the VERSATILE-002 clinical trial among a gathering of the world’s leading members of the clinical and scientific oncology community at ESMO (Free ESMO Whitepaper) Congress 2023," stated Lauren V. Wood, M.D., PDS Biotech’s Chief Medical Officer and a co-author of the study. "The incidence of HPV-positive head and neck cancers is growing rapidly, and there is currently a lack of effective targeted therapies to address this population. To date, multiple studies in early-stage and advanced cancer patients have demonstrated the ability of PDS0101 to induce high levels of active and potent HPV16-specific CD4 and CD8 multifunctional T cells, as well as long-lasting memory CD8 T cells, substantiating the potential for PDS0101 combined with KEYTRUDA to expand the range of treatments addressing HPV16-positive head and neck cancers."

Abstract Title: Polyfunctional HPV16-Specific T cell responses in subjects receiving PDS0101 and pembrolizumab combination treatment for recurrent/metastatic HPV16-positive head and neck squamous cell carcinoma (HNSCC)
Abstract Number: 6982
Presenting Author: Dr. Kevin Harrington, Ph.D., Professor of Biological Cancer Therapies, The Royal Marsden
Authors: K. Harrington, J. Weiss, K. Price, J. Kaczmar, D. Schaaf, N. Riebel, S. Jones, A. Cotty, S. McCarthy, L. Wood

For patients interested in enrolling in this clinical trial, please contact NCI’s toll-free number 1-800-4-Cancer (1-800-422-6237) (TTY: 1-800-332-8615) and/or the Web site: View Source and/or [email protected].

About PDS0101
PDS0101, PDS Biotech’s lead candidate, is a novel investigational human papillomavirus (HPV)-targeted immunotherapy that stimulates a potent targeted T cell attack against HPV-positive cancers. PDS0101 is given by subcutaneous injection alone or in combination with other immunotherapies and cancer treatments. In a Phase 1 study of PDS0101 in monotherapy, the treatment demonstrated the ability to generate multifunctional HPV16-targeted CD8 and CD4 T cells with minimal toxicity. Interim data suggests PDS0101 generates clinically effective immune responses and the combination of PDS0101with other treatments can demonstrate significant disease control by reducing or shrinking tumors, delaying disease progression, and/or prolonging survival. The combination of PDS0101 with other treatments does not appear to compound the toxicity of other agents.

About VERSATILE-002
VERSATILE-002 is a single-arm Phase 2 trial evaluating the safety and efficacy of PDS0101, an HPV16-targeted investigational T cell-activating immunotherapy that leverages PDS Biotech’s proprietary Versamune technology, in combination with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab). The combination is being evaluated in immune checkpoint inhibitor (ICI)-naïve and ICI-refractory patients with recurrent/metastatic HPV16-positive head and neck squamous cell carcinoma (HNSCC) and was granted Fast Track designation by the Food and Drug Administration in June 2022.

Interim efficacy and safety data will be presented at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting for ICI-naïve patients. Preliminary data from the first 34 patients demonstrated a 12-month overall survival rate of 87% and median progression free survival of 10.4 months. No Grade 4 or higher treatment related adverse events were observed.

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

On July 25, 2023 Nymox Pharmaceutical Corporation [OTC: NYMXF] (the "Company") reported important new long-term clinical trial results from the Company’s 146 patient NX03-0040 NYMOZARFEX (TM) U.S. study for low grade localized prostate cancer (Press release, Nymox, JUL 25, 2023, View Source [SID1234633414]). New long-term follow-up data from the prospective randomized clinical trial of NYMOZARFEX (TM) for low grade early prostate cancer has indicated that there is strong statistically significant benefit from the treatment compared to controls when all available patient outcomes were included from 18 months to as long as up to >10 years after treatment.

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These additional 5 to 10-year data points add to the 5-year data that was published in the peer review World Journal of Urology in 2020 (World J Urol 38, 3101–3111 (2020). View Source). All clinical trial sites that were still open were contacted for follow-up data on the prostate cancer status of all available patients. A full effort was made to reach all possible subjects. The outcome comparisons showed greatly reduced percentages of subjects treated with NYMOZARFEX (TM) who had progressed by either cancer grade worsening or by prostate cancer surgery, radiotherapy, or chemotherapy; and which remained overall strongly statistically significant compared to the study’s randomized controls (p<.01).

This unique and successful study is the world’s first and only long-term prospective randomized controlled study of an intraprostatic molecular injectable treatment for low-grade localized prostate cancer to have been accomplished. The new data represents the longest term data available from this major study.

Study NX03-0040 was undertaken starting in 2012 at investigational sites across the U.S. with 146 men with the biopsy confirmed diagnosis of Grade Group1 prostate cancer. NYMOZARFEX (TM) was administered by a single painless injection directly into the prostate in a relatively simple procedure requiring several minutes or less in an office setting without sedation or anesthesia, and guided by routine ultrasound. NYMOZARFEX (TM) was injected into the area of the prostate where the cancer was previously detected prior to enrollment in NX03-0040. The patients were then biopsied after 6 weeks and then every 18 months, along with serial PSA measurements and long-term follow-up.

All subjects with 18 months or more follow-up were compared with the inclusion of follow-up data from up to 10 years or more after a single injection of NYMOZARFEX (TM). For the patients where investigational sites were closed or where patients for unrelated reasons were no longer available, the last known status reports were included if they were 18 months or longer. For any subject with a worsening (increase) in grade of prostate cancer on biopsy; or with prostate cancer surgery, or radiotherapy or chemotherapy, they were included regardless of time after study treatment, and were counted in the calculation as treatment failures. The data shows that the number of patients with one focal injection of NYMOZARFEX (TM) 15 mg directed at the tumor had significantly less progression to more advanced cancer or to major cancer treatments, than the randomized control subjects followed in the study.

Dr. Paul Averback, CEO of Nymox said, "We are very excited about this major step forward for NYMOZARFEX (TM) which represents a first in class painless and well tolerated treatment approach for the very important condition of low grade localized prostate cancer. NYMOZARFEX (TM) treatment has shown persistent long-term benefit in this large study, where there was statistically significant less progression of the cancer in men who received the drug injection. The Company will soon be taking steps for meetings with regulatory authorities concerning marketing goals for NYMOZARFEX (TM). There is a global unmet medical need for more effective low-grade prostate cancer treatments that produce minimal collateral tissue damage and undesirable risks and often permanent unintended sexual, urinary, and bowel function side effects."

Nymox CEO added, "We further emphasize that NYMOZARFEX (TM) has also been shown to be associated with a significant reduction in the incidence of new prostate cancer in men suffering from BPH (benign prostatic hyperplasia). That other evidence which was initially unexpected came from patients who received NYMOZARFEX (TM) for their BPH in Nymox’s long-term studies of 977 men with BPH in the U.S. as part of Nymox’s pivotal Phase 3 BPH clinical program. Both 1) the long-term data reported here today involving prospective planned treatment of biopsy established low grade localized cancers, and 2) the unexpected long-term prevention of new onset confirmed cancer in BPH patients reported previously, together indicate that NYMOZARFEX (TM) has shown significant efficacy in men for the treatment and prevention of prostate cancer, without the risks and undesirable side effects generally associated with treatment of these conditions."

Low grade localized prostate cancer (Gleason 3+3; T1c) is a very common treatment problem. The Nymox study reported today involves patients with initially Gleason grade 3+3 or lower. These patients are found to have these tumors by biopsy which is usually instituted after finding abnormalities in PSA levels, and/or after abnormal digital rectal examination of the prostate, and/or after the patient has experienced lower urinary tract symptoms or other changes. Low grade localized prostate cancer represents a therapeutic challenge. Because of its slow growth and low initial level of malignancy, urologists and patients can be reluctant to proceed to invasive surgical treatments or radiotherapy due to the unpleasant and often permanent side effects these treatments cause in the genitourinary tract, such as sexual functional issues and/ or urinary issues. Eventually if and when the tumor progresses, invasive surgical and/or radiotherapeutic procedures become necessary, with greater risk due to the progression. Occasionally the tumors become highly malignant after variable lengths of time. These risks cause understandable anxieties and distress and many men prefer to advance to invasive therapy before running these risks of higher grade cancers. It is widely acknowledged that a treatment like NYMOZARFEX (TM) that can destroy or ablate the low grade cancers of the prostate without the dreaded side effects and morbidities, would be an important benefit for these patients.

Prostate cancer is the most commonly diagnosed cancer in men, other than skin cancer, and is the second leading cause of cancer death for men. Approximately 50% of prostate cancers are initially considered low risk. One of the major problems with the main current prostate treatments for localized prostate cancer (radical prostatectomy, external beam radiation, brachytherapy) is the relatively high incidence of serious sexual and other problems post- treatment. In 9 studies, NYMOZARFEX (TM) treatment has been shown to have a negligible significant adverse effect profile post-treatment and no significant adverse effects on sexual or other functions or testosterone levels.

Leading urologists have long recognized the unmet need for prostate cancer treatments that can contribute to improved outcomes for their patients together with reduced side effects and stresses that may have significantly impact on quality of life. The goal of NYMOZARFEX (TM) injectable is to allow for an initial and less toxic treatment for low-risk prostate cancer patients, achieving the benefits of molecular ablation with minimal risk of side effects. For many patients, this treatment combined with surveillance would be extremely helpful for the unpleasant and persistent uncertainties, anxieties, and psychological/emotional burdens associated with only selecting active surveillance.

About NYMOZARFEX (TM) (Fexapotide)

NYMOZARFEX (TM) is given in an in-office procedure that is administered in a few minutes without need of anesthesia or analgesia. The drug has been tested in clinical trials involving overall more than 1750 patients with over 1600 injections administered including over 1200 Fexapotide administrations. Fexapotide has led to significant long-term improvements and has shown an excellent safety profile without the side effects normally associated with existing BPH treatments.

There is an important unmet need in the global middle aged and elderly male population for effective treatment for prostate enlargement (known as BPH, benign prostatic hyperplasia). BPH affects up to half the global male population after late middle age, and the vast majority of men have the condition when they reach their mid-70’s and older. Current medical treatments are intended for life-long treatment but are hindered by intolerable side effects that many or most men experience, and they stop treatment usually in the first year or two. These side effects can be sexual problems or a variety of other issues, some of which are more serious such as hypotension, depression, possible increased risk of prostate cancer, retrograde ejaculation, and many others. Surgical treatments are effective usually, but have the drawbacks of surgical pain, anesthesia, catheterizations, complications and other risks such as the frequent permanence of retrograde ejaculation, and occasional need for re-treatments.

For more information please contact [email protected] or 800-936-9669.

On July 25, 2023 Kiniksa Pharmaceuticals, Ltd. (Nasdaq: KNSA) (Kiniksa), a biopharmaceutical company with a pipeline of immune-modulating assets designed to target a spectrum of cardiovascular and autoimmune diseases, reported second quarter 2023 financial results and recent portfolio execution (Press release, Kiniksa Pharmaceuticals, JUL 25, 2023, View Source [SID1234633413]).

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"Kiniksa continues to make significant progress in bringing ARCALYST, the first and only FDA-approved therapy for recurrent pericarditis, to patients in need. As a result of increased call frequency and expanded reach with target prescribers, we are seeing increased prescriber adoption and patient enrollments. We are still in the early stages of building the recurrent pericarditis market and remain encouraged by the high level of patient satisfaction, payer approval rates, and duration of therapy. These key metrics provide conviction in raising our 2023 ARCALYST sales guidance to between $220 million and $230 million," said Sanj K. Patel, Chairman and Chief Executive Officer of Kiniksa. "Within our pipeline, we continue to enroll patients in the KPL-404 Phase 2 trial in rheumatoid arthritis and expect data in the first half of 2024. Additionally, we have a strong financial position and our cash reserves, combined with our continued ARCALYST commercial execution and financial discipline, now provide cash runway into at least 2027."

Portfolio and Collaboration Execution

ARCALYST (IL-1α and IL-1β cytokine trap)

• ARCALYST net product revenue was $54.5 million for the second quarter of 2023.

• Since launch, more than 1,250 prescribers have written ARCALYST prescriptions for recurrent pericarditis.

• As of the end of the second quarter of 2023, average total duration of ARCALYST therapy in recurrent pericarditis was approximately 20 months.

- Average total duration of therapy includes the approximately 45% of patients who restarted ARCALYST, within an average of 8 weeks, after having discontinued therapy.

KPL-404 (monoclonal antibody inhibitor of CD40-CD154 interaction)

• Kiniksa is enrolling patients in the Phase 2 clinical trial of KPL-404 in rheumatoid arthritis. The company expects data from the trial in the first half of 2024.

Mavrilimumab (monoclonal antibody inhibitor targeting GM-CSFRα)

• Kiniksa is pursuing collaborative study agreements to evaluate the potential of mavrilimumab in rare cardiovascular diseases where the granulocyte macrophage colony stimulating factor (GM-CSF) mechanism has been implicated.

Vixarelimab (monoclonal antibody inhibitor of signaling through OSMRβ)

• In the second quarter of 2023, Kiniksa recognized a $15.0 million development milestone related to a new indication under its global license agreement with Genentech, a member of the Roche Group (Genentech).

Financial Results

• Total revenue for the second quarter of 2023 was $71.5 million, compared to $27.0 million for the second quarter of 2022.

- Total revenue for the second quarter of 2023 included $54.5 million in ARCALYST net product revenue and $17.0 million in license and collaboration revenue, compared to $27.0 million in ARCALYST net product revenue and $0.0 million in license and collaboration revenue for the second quarter of 2022.

• Total operating expenses for the second quarter of 2023 were $74.6 million, compared to $46.3 million for the second quarter of 2022.

- Total operating expenses for the second quarter of 2023 included $6.5 million in non-cash, share-based compensation expense, compared to $6.7 million for the second quarter of 2022.

• Net income for the second quarter of 2023 was $15.0 million, compared to a net loss of $20.0 million for the second quarter of 2022.

- Net income for the second quarter of 2023 included a $16.2 million tax benefit primarily due to the release of a valuation allowance on non-cash deferred tax assets.

• As of June 30, 2023, Kiniksa had $185.0 million of cash, cash equivalents, and short-term investments and no debt.

2

Financial Guidance

• Kiniksa now expects 2023 ARCALYST net product revenue of between $220 million and $230 million compared to prior guidance of between $200 million and $215 million.

• Kiniksa now expects that its cash and cash equivalents will fund its current operating plan into at least 2027.

Conference Call Information

• Kiniksa will host a conference call and webcast at 8:30 a.m. Eastern Time on Tuesday, July 25, 2023, to discuss second quarter 2023 financial results and recent portfolio execution.

• Individuals interested in participating in the call via telephone may register here. Upon registration, all telephone participants will receive a confirmation email detailing how to join the conference call, including the dial-in number along with a unique passcode and registrant ID that can be used to access the call. To access the webcast, please visit the Investors and Media section of Kiniksa’s website. A replay of the event will also be available on Kiniksa’s website within approximately 48 hours after the event.

On July 25, 2023 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported the presentation of updated exploratory subgroup analyses from the SIENDO study (NCT03555422) in patients with advanced or recurrent TP53 wild-type endometrial cancer at the virtual American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Plenary Series (Press release, Karyopharm, JUL 25, 2023, View Source [SID1234633412]).

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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 TP53 wild-type is found in approximately 50% of advanced/recurrent tumors in patients with endometrial cancer.2,3 TP53 wild-type is observed in both MSS (pMMR) and MSI-H (dMMR) populations. Recently there has been progress in potential treatment options in the MSI-H (dMMR) subgroup with new targeted treatments. However, a large unmet need continues to exist for MSS (pMMR), which comprises approximately 70% of all endometrial cancer patients and of that population, approximately 70% are TP53 wild-type.

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 SIENDO study, 263 patients were randomly assigned, with 174 patients allocated to the selinexor arm and 89 patients to the placebo arm. One hundred and thirteen patients with TP53 wild-type endometrial cancer were randomized to receive selinexor (n=77) vs placebo (n=36) as maintenance therapy. As of the March 30, 2023 data cut-off date, and a median duration of follow-up of 25.3 months, selinexor-treated patients with TP53 wild-type endometrial cancer had a median PFS of 27.4 months compared to 5.2 months for patients with TP53 wild-type endometrial cancer receiving placebo. Additionally, median PFS was not reached for selinexor-treated TP53 wild-type MSS (pMMR) endometrial cancer patients compared to 4.9 months for TP53 wild-type MSS (pMMR) endometrial cancer patients treated with placebo.

No new safety signals were identified as of the last data cut-off date on March 30, 2023. The most common adverse events (AEs) in TP53 wild-type patients were nausea (91%), vomiting (61%) and diarrhea (40%), the majority of which were grades 1-2. The most common reported grade 3-4 treatment-emergent AEs (TEAEs) included neutropenia (18%), nausea (12%), and thrombocytopenia (9%). TEAEs leading to discontinuations were reported in 16% of patients.

The SIENDO exploratory subgroup data provides further rationale for the ongoing pivotal Phase 3 study (XPORT-EC-042; NCT05611931) of selinexor as a maintenance therapy following systemic therapy in patients with TP53 wild-type advanced or recurrent endometrial cancer with the strongest signal in TP53 wild-type, MSS (pMMR). Karyopharm is currently enrolling patients in the pivotal Phase 3 study of selinexor as a maintenance therapy following systemic therapy in patients with TP53 wild-type advanced or recurrent endometrial cancer (XPORT-EC-042; NCT05611931) to better understand the exploratory subgroup analysis. This trial includes a companion diagnostic tool under development by Foundation Medicine, Inc. 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.

"The updated results from SIENDO suggest that selinexor may have the potential to prolong systemic therapy response in patients whose disease is TP53 wild-type. Particularly encouraging are the data observed in the subgroup of patients whose disease are both TP53 wild-type and MSS," said Reshma Rangwala, MD, PhD, Chief Medical Officer of Karyopharm. "We are encouraged by the updated results from this study as it further strengthens the rationale for our ongoing EC-042 Phase 3 study."

"Treatment options for women with advanced or recurrent endometrial cancer are rapidly evolving with the identification of molecular subgroups. Limited options, however, still persist among certain subgroups, including patients with mismatch repair-proficient disease (pMMR), who comprise about 70% of endometrial cancers," said Dr. Ignace Vergote, principal investigator and gynecologist oncologist, ENGOT and the Belgium and Luxembourg Gynaecological Oncology Group (BGOG), University of Leuven, Leuven Cancer Institute, Leuven, Belgium. "TP53 is a well-recognized molecular marker in endometrial cancer. About 50% of patients with advanced, recurrent endometrial cancer have disease identified as TP53 wild-type and about 70% of those further classified as a pMMR. The EC-042 study is designed to show that inhibition of XPO1 with selinexor may provide a potential new therapeutic option for these patients."

"The long-term follow-up in the TP53 wild-type subgroup from the SIENDO trial is extremely encouraging and suggests that TP53 status could be an important biomarker that can identify patients who benefit from XPO1 inhibition with selinexor," said Dr. Brian Slomovitz, Director of Gynecologic Oncology and Co-Chair of the Cancer Research Committee at Mount Sinai Medical Center, and Uterine Cancer Trial Advisor for GOG Partners, Inc. "Given the unmet need that remains for patients whose disease is pMMR as well as the encouraging exploratory data in the subgroup of patients who are classified as TP53 wild-type and pMMR, a potential new paradigm for both the diagnosis and treatment of women with endometrial cancer may be identified. I look forward to the ongoing progress of EC-042 to further explore this hypothesis."

ASCO Plenary Series Program
Title: Long-term follow up of selinexor maintenance in patients with TP53wt advanced or recurrent endometrial cancer: A pre-specified subgroup analysis from the phase 3 ENGOT-EN5/GOG-3055/SIENDO study.
Presenter: Brian Slomovitz, MD, Mount Sinai Medical Center
Session Date and Time: Tuesday July 25, 2023, 3:00pm – 4:00pm (ET)
This livestream event presented by ASCO (Free ASCO Whitepaper) is free to register at:
View Source

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.