On December 11, 2020 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported that the National Comprehensive Cancer Network (NCCN) added three different XPOVIO (selinexor) combination regimens to its Clinical Practice Guidelines in Oncology (NCCN Guidelines) for previously treated multiple myeloma (Press release, Karyopharm, DEC 11, 2020, View Source [SID1234572706]). The XPOVIO regimens added to the NCCN guidelines, include: (i) selinexor / bortezomib / dexamethasone (once-weekly) (SVd); (ii) selinexor / daratumumab / dexamethasone (SDd); and (iii) selinexor / pomalidomide / dexamethasone (SPd), which is an all-oral treatment regimen. Importantly, the once weekly SVd regimen received a Category 1 recommendation, which represents the highest designation assigned by NCCN indicating the recommendation is based upon high-level evidence and that there is uniform NCCN consensus that the intervention is appropriate.

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"We are honored to have XPOVIO receive this important recognition through its addition to the NCCN Guidelines," said Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm. "The NCCN Guidelines are utilized by healthcare providers across the country to inform optimal treatment decision making. The inclusion of three different XPOVIO combination regimens into these guidelines further validates the importance XPOVIO may have in the future multiple myeloma treatment landscape."

The NCCN is a not-for-profit alliance of 30 leading cancer centers devoted to patient care, research, and education. The NCCN Guidelines are a comprehensive set of guidelines detailing the sequential management decisions and interventions that currently apply to 97% of cancers affecting patients in the U.S and are intended to ensure that all patients receive preventive, diagnostic, treatment, and supportive services that will most likely lead to optimal outcomes.

Karyopharm’s supplemental New Drug Application requesting approval for XPOVIO as a treatment for patients with multiple myeloma who have received one prior line of therapy has been assigned an FDA action date of March 19, 2021 under the Prescription Drug User-Fee Act.

About XPOVIO (selinexor)

XPOVIO is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). XPOVIO blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion. Karyopharm received accelerated U.S. Food and Drug Administration (FDA) approval of XPOVIO in July 2019 in combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) 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. Karyopharm has also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) with a request for conditional approval of selinexor in this same RRMM indication. Karyopharm’s supplemental New Drug Application (sNDA) requesting an expansion of its current indication to include the treatment for patients with multiple myeloma after at least one prior line of therapy has been accepted for filing by the FDA. In June 2020, Karyopharm received accelerated FDA approval of XPOVIO for its second indication in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including as a potential backbone therapy in combination with approved myeloma therapies (STOMP), in liposarcoma (SEAL) and in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm’s clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

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]

IMPORTANT SAFETY INFORMATION

Thrombocytopenia: XPOVIO can cause life-threatening thrombocytopenia, potentially leading to hemorrhage. Thrombocytopenia was reported in patients with multiple myeloma (MM) and developed or worsened in patients with DLBCL.

Thrombocytopenia is the leading cause of dosage modifications. Monitor platelet counts at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Institute platelet transfusion and/or other treatments as clinically indicated. Monitor patients for signs and symptoms of bleeding and evaluate promptly. Interrupt, reduce dose, or permanently discontinue based on severity of adverse reaction.

Neutropenia: XPOVIO can cause life-threatening neutropenia, potentially increasing the risk of infection. Neutropenia and febrile neutropenia occurred in patients with MM and in patients with DLBCL.

Obtain white blood cell counts with differential at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Monitor patients for signs and symptoms of concomitant infection and evaluate promptly. Consider supportive measures, including antimicrobials and growth factors (e.g., G-CSF). Interrupt, reduce dose, or permanently discontinue based on severity of adverse reaction (AR).

Gastrointestinal Toxicity: XPOVIO can cause severe gastrointestinal toxicities in patients with MM and DLBCL.

Nausea/Vomiting: Provide prophylactic antiemetics. Administer 5-HT3 receptor antagonists and other anti-nausea agents prior to and during treatment with XPOVIO. Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Administer intravenous fluids to prevent dehydration and replace electrolytes as clinically indicated.

Diarrhea: Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Provide standard anti-diarrheal agents, administer intravenous fluids to prevent dehydration, and replace electrolytes as clinically indicated.

Anorexia/Weight Loss: Monitor weight, nutritional status, and volume status at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Provide nutritional support, fluids, and electrolyte repletion as clinically indicated.

Hyponatremia: XPOVIO can cause severe or life-threatening hyponatremia. Hyponatremia developed in patients with MM and in patients with DLBCL.

Monitor sodium level at baseline and throughout treatment. Monitor more frequently during the first 2 months of treatment. Correct sodium levels for concurrent hyperglycemia (serum glucose >150 mg/dL) and high serum paraprotein levels. Assess hydration status and manage hyponatremia per clinical guidelines, including intravenous saline and/or salt tablets as appropriate and dietary review. Interrupt, reduce dose, or permanently discontinue based on severity of the AR.

Serious Infection: XPOVIO can cause serious and fatal infections. Most infections were not associated with Grade 3 or higher neutropenia. Atypical infections reported after taking XPOVIO include, but are not limited to, fungal pneumonia and herpesvirus infection.

Monitor for signs and symptoms of infection, and evaluate and treat promptly.

Neurological Toxicity: XPOVIO can cause life-threatening neurological toxicities.

Coadministration of XPOVIO with other products that cause dizziness or mental status changes may increase the risk of neurological toxicity.

Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, until the neurological toxicity fully resolves. Optimize hydration status, hemoglobin level, and concomitant medications to avoid exacerbating dizziness or mental status changes. Institute fall precautions as appropriate.

Embryo-Fetal Toxicity: XPOVIO can cause fetal harm when administered to a pregnant woman.

Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with a female partner of reproductive potential to use effective contraception during treatment with XPOVIO and for 1 week after the last dose.

ADVERSE REACTIONS

The most common adverse reactions (ARs) in ≥20% of patients with MM are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and upper respiratory tract infection.

The most common ARs, excluding laboratory abnormalities, in ≥20% of patients with DLBCL are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3-4 laboratory abnormalities in ≥15% of patients included thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. Grade 4 laboratory abnormalities in ≥5% were thrombocytopenia, lymphopenia, and neutropenia.

In patients with MM, fatal ARs occurred in 9% of patients. Serious ARs occurred in 58% of patients. Treatment discontinuation rate due to ARs was 27%. The most frequent ARs requiring permanent discontinuation in ≥4% of patients included fatigue, nausea, and thrombocytopenia.

In patients with DLBCL, fatal ARs occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal AR was infection (4.5% of patients). Serious ARs occurred in 46% of patients; the most frequent serious AR was infection. Discontinuation due to ARs occurred in 17% of patients.

USE IN SPECIFIC POPULATIONS

In MM, no overall difference in effectiveness of XPOVIO was observed in patients >65 years old when compared with younger patients. Patients ≥75 years old had a higher incidence of discontinuation due to an AR than younger patients, a higher incidence of serious ARs, and a higher incidence of fatal ARs.

Clinical studies in patients with relapsed or refractory DLBCL did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.

The effect of end-stage renal disease (CLCR <15 mL/min) or hemodialysis on XPOVIO pharmacokinetics is unknown.

On December 11, 2020 Sutro Biopharma, Inc. (Nasdaq: STRO), a clinical-stage drug discovery, development and manufacturing company focused on the application of precise protein engineering and rational design to create next-generation cancer and autoimmune therapeutics, reported the closing of its upsized public offering of 6,900,000 shares of its common stock at a public offering price of $21.00 per share, which includes the exercise in full of the underwriters’ option to purchase 900,000 shares of common stock (Press release, Sutro Biopharma, DEC 11, 2020, View Source [SID1234572704]). The gross proceeds from this offering were $144.9 million, before deducting underwriting discounts and commissions and other offering expenses payable by Sutro.

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Cowen, Piper Sandler and Wells Fargo Securities acted as joint book-running managers in the offering. Wedbush PacGrow and JMP Securities acted as co-managers in the offering.

Sutro intends to use the net proceeds from the proposed offering, together with its existing cash, cash equivalents and marketable securities, to fund the continued clinical development of STRO-001 and STRO-002 and the remainder to fund the further development of its technology platform, including manufacturing, to broaden its pipeline of product candidates, and for working capital and general corporate purposes.

The shares were offered by Sutro pursuant to registration statements previously filed and declared effective by the Securities and Exchange Commission (SEC). A final prospectus supplement and the accompanying prospectus relating to this offering have been filed with the SEC. Copies of the final prospectus supplement may be obtained from: Cowen and Company, LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, New York 11717, Attn: Prospectus Department, by telephone at (833) 297-2926, or by email at [email protected]; Piper Sandler & Co., Attention: Prospectus Department, 800 Nicollet Mall, J12S03, Minneapolis, Minnesota 55402, by telephone at (800) 747-3924, or by email at [email protected]; or Wells Fargo Securities, LLC, Attention: Equity Syndicate Department, 500 West 33rd Street, New York, New York 10001, by telephone at (800) 326-5897, or by email at [email protected]. Electronic copies of the final prospectus supplement and accompanying prospectus will also be available on the website of the SEC at View Source

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

On December 11, 2020 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, reported efficacy and safety outcomes in a subgroup of patients from the NALA trial who had central nervous system (CNS) metastases at baseline, with a particular focus on CNS-specific endpoints, at the 2020 Virtual San Antonio Breast Cancer Symposium (SABCS) that is currently taking place (Press release, Puma Biotechnology, DEC 11, 2020, View Source [SID1234572700]). The presentation, entitled "Impact of neratinib plus capecitabine on outcomes in HER2-positive metastatic breast cancer patients with central nervous system disease at baseline: Findings from the phase 3 NALA trial," is being presented at a Spotlight Poster Discussion Session by Cristina Saura, M.D., Ph.D., Head of Breast Cancer Unit, Vall d’Hebrón University Hospital, an investigator of the trial. A copy of this poster presentation is available on the Puma website.

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The Phase III NALA trial was a randomized controlled trial of neratinib plus capecitabine (N+C) versus Tykerb (lapatinib) plus capecitabine (L+C) in patients with third-line HER2-positive metastatic breast cancer (NCT01808573). The trial enrolled 621 patients who were randomized (1:1) to receive either N+C or L+C. The co-primary endpoints of the trial were independently adjudicated progression free survival (PFS) and overall survival (OS). The NALA study met its primary endpoint, with the neratinib arm having significantly improved PFS vs. the lapatinib arm (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.63-0.93; stratified log-rank P = .0059; mean PFS 8.8 mo vs. 6.6 mo). The data showed no statistical difference in OS between treatment arms (HR 0.88; 95% CI, 0.72-1.07; P = .2098). Time to intervention for symptomatic central nervous system disease (also referred to as brain metastases) was a predefined secondary endpoint of the trial. In the ITT population, significantly fewer interventions for CNS disease occurred with N+C versus L+C (cumulative incidence, 22.8% vs. 29.2%; P = .043).

The poster presented at the 2020 SABCS meeting describes results for the subset of patients who entered the trial with CNS metastases. Of the 621 patients randomized to study treatment, 101 (16.3%) had asymptomatic CNS metastases at baseline (N+C, n=51; L+C, n=50). Within the CNS at baseline subgroup, the data suggested an association between N+C and improved PFS compared with L+C (HR 0.66; 95% CI, 0.41-1.05). The mean PFS was 7.8 months in the neratinb arm vs. 5.5 months in the laptinib arm. Consistent with results in the overall population, there was no apparent difference in OS between arms in the CNS at baseline group. With respect to the CNS-specific outcomes, N+C was associated with fewer interventions for CNS disease compared with L+C; the 12 month incidence of interventions for CNS metastases was 25.5% in the N+C arm and 36.0% in the L+C arm. The data also suggested an association between neratinib and improved CNS progression free survival (CNS-PFS), an ad hoc composite endpoint assessing disease progression in the brain or death from any cause (HR 0.62; 95% CI, 0.32-1.18). The median CNS-PFS was 12.4 months in the patients treated with N+C and 8.3 months in the patients treated with L+C.

As described in the poster, a unique feature of the NALA trial was the inclusion of patients with leptomeningeal disease (LMD), two of whom were treated with N+C with good outcomes (progression after 5.6 and 9.8 months, and OS times of 17.4 and 19.8 months, respectively). One patient with LMD received L+C and had disease progression after 4.3 months and an OS of 6.5 months.

The safety profile in patients with CNS metastases at baseline was consistent with that observed in the overall NALA safety population. Diarrhea, nausea, vomiting, and palmar-plantar erythrodysesthesia syndrome were the most common adverse events. Common CNS adverse events (grade 1-4) included headache (N+C, 18% vs L+C, 29%), dizziness (18% vs. 16%), hemiparesis (4% vs. 4%), seizure (4% vs. 4%), and gait disturbance (0% vs. 8%).

Cristina Saura, M.D., Ph.D., Head of Breast Cancer Unit, Vall d’Hebrón University Hospital, said, "The data suggest an association between neratinib and improved PFS and CNS outcomes in patients with CNS metastases from HER2-positive metastatic breast cancer. These findings are consistent with three other prospective studies."

Alan H. Auerbach, Chief Executive Officer and President of Puma, added, "CNS metastases from HER2-positive breast cancer present a clinical challenge due to the limited availability of effective treatments. These findings from the NALA trial add to the growing body of data on the efficacy of neratinib in patients with HER2 positive metastatic breast cancer that has metastasized to the brain and may suggest a role for neratinib as a systemic treatment option in the management of patients with HER2-positive brain metastases following antibody-based HER2-directed therapies."

About HER2-Positive Breast Cancer

Up to 20% of patients with breast cancer tumors over-express the HER2 protein (HER2-positive disease) and in the ExteNET study, 57% of patients were found to have tumors that were hormone-receptor positive. HER2-positive breast cancer is often more aggressive than other types of breast cancer, increasing the risk of disease progression and death. Although research has shown that trastuzumab can reduce the risk of early stage HER2-positive breast cancer recurring, up to 25% of patients treated with trastuzumab experience recurrence within 10 years, the majority of which are metastatic recurrences.

On December 11, 2020 CEL-SCI Corporation (NYSE American: CVM), a Phase 3 cancer immunotherapy company, reported the closing of the offering of 1,000,000 shares of its common stock at a price of $14.65 per share, for total gross proceeds of $14.65 million, before deducting underwriting discounts and other offering expenses payable by the Company (Press release, Cel-Sci, DEC 11, 2020, View Source [SID1234572697]). Additionally, the Company has granted the underwriter a 30-day option to purchase up to 150,000 additional shares to cover over-allotments.

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Kingswood Capital Markets, division of Benchmark Investments, Inc. and Aegis Capital Corp. acted as the joint book-running managers for the offering.

This offering was made pursuant to a "shelf" registration statement on Form S-3 (File No. 333-226558) filed with the Securities and Exchange Commission (SEC). A prospectus supplement and accompanying base prospectus relating to the offering were filed with the SEC and are available on the SEC’s website at View Source and may be obtained from Kingswood Capital Markets, Attention: Syndicate Desk, 17 Battery Place, Suite 625, New York, NY 10004, by email at [email protected], or by telephone at (212) 404-7002.

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

On December 11, 2020 Agendia, Inc., a world leader in precision oncology for breast cancer, reported that additional data from its groundbreaking MINDACT study will be highlighted in an oral presentation by Laura van ’t Veer, Ph.D., Co-founder and Chief Research Officer, at the 2020 San Antonio Breast Cancer Symposium (SABCS 2020) (Press release, Agendia, DEC 11, 2020, View Source [SID1234572696]). These data highlight the ability of MammaPrint, Agendia’s 70-gene breast cancer recurrence assay, to further stratify patients with clinically low risk breast cancer which could impact physician-patient discussions and treatment planning.

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MINDACT (​M​icroarray ​I​n ​N​ode-Negative and 1-3 node-positive ​D​isease may ​A​void Chemo​T​herapy), the Phase 3, prospective, randomized clinical trial supported by the European Organization for Research and Treatment of Cancer (EORTC), was designed to determine whether MammaPrint could be used to safely de-escalate patients with early stage breast cancer from chemotherapy without compromising their outcomes. Updated outcome and treatment data from the trial shared at SABCS 2020 build upon nearly 9-year follow-up results debuted at ASCO (Free ASCO Whitepaper) 2020 and confirm MINDACT as a positive de-escalation study.

Dr. van ’t Veer’s presentation showed that the combination of clinical low risk and MammaPrint Low Risk results indicate excellent 8-year prognosis – these patients showed a distant metastasis-free survival rate of 94.7% with no chemotherapy. Of note, amongst the clinically low risk study population, distant metastasis free survival at 8 years was 3.6% better in MammaPrint Low Risk patients as compared to those with a High Risk result.

"Collectively, these data produce a significant library of evidence that will allow for the precise treatment of breast cancer, including insights into a patient population considered low risk," said Dr. van ’t Veer. "Within this population, further stratification by genomic signature into MammaPrint Low or High Risk should be weighed for further treatment planning."

These data are part of a large suite of 13 posters, spotlight sessions and an oral presentation on MammaPrint and BluePrint that were accepted to SABCS 2020, and underscore Agendia’s mission to help guide the diagnosis and personalized treatment of breast cancer for all patients throughout their treatment journey.