Karyopharm Therapeutics Announces Pricing of $150 Million of Convertible Senior Notes

On October 11, 2018 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, reported the pricing of $150 million aggregate principal amount of its 3.00% convertible senior notes due 2025 (the "Notes") (Press release, Karyopharm, OCT 11, 2018, View Source [SID1234530278]). The Notes will be sold in a private offering to qualified institutional buyers in reliance on Rule 144A under the Securities Act of 1933, as amended (the "Securities Act"). Karyopharm also granted to the initial purchasers of the Notes a 13-day option to purchase up to an additional $22.5 million aggregate principal amount of the Notes. The offering is expected to close on or about October 16, 2018, subject to satisfaction of customary closing conditions.

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The Notes will be unsecured, senior obligations of Karyopharm, and will bear interest at a rate of 3.00% per annum, payable semi-annually in arrears on April 15 and October 15 of each year, beginning on April 15, 2019. The Notes will mature on October 15, 2025, unless earlier repurchased, redeemed or converted in accordance with their terms. Subject to certain conditions, on or after October 15, 2022, Karyopharm may redeem for cash all or a portion of the Notes at a redemption price equal to 100% of the principal amount of the Notes to be redeemed, plus accrued and unpaid interest, if any, to, but excluding, the redemption date. The Notes will be convertible at the option of holders of the Notes, upon satisfaction of certain conditions and during certain periods, into cash, shares of Karyopharm’s common stock, or a combination of cash and shares of Karyopharm’s common stock, at Karyopharm’s option. The conversion rate for the Notes will initially be 63.0731 shares of Karyopharm’s common stock per $1,000 principal amount of Notes, which is equivalent to an initial conversion price of approximately $15.85 per share. This represents a premium of approximately 27.5% over the last reported sale price of $12.435 per share of Karyopharm’s common stock on The Nasdaq Global Select Market on October 10, 2018. The conversion rate will be subject to adjustment upon the occurrence of certain events.

Karyopharm estimates that the net proceeds from the sale of the Notes will be approximately $145.1 million (or approximately $167.0 million if the initial purchasers exercise their option to purchase additional Notes in full), after deducting the initial purchasers’ discounts and commissions and estimated offering expenses payable by Karyopharm. Karyopharm intends to use the net proceeds from the sale of the Notes: to continue establishing the infrastructure to support the potential commercial launch of selinexor; to support continued clinical development of selinexor in hematologic malignancies and solid tumors; to conduct ongoing activities to support regulatory submissions for oral selinexor as a new treatment for patients with penta-refractory multiple myeloma and, if the results of Karyopharm’s SADAL trial are positive, as a new treatment for patients with relapsed/refractory diffuse large B-cell lymphoma; for clinical trials of two of Karyopharm’s pipeline drug candidates in oncology, eltanexor and KPT-9274; and for working capital and other general corporate purposes.

The Notes will be offered and sold to qualified institutional buyers pursuant to Rule 144A under the Securities Act. The offer and sale of the Notes and the shares of common stock issuable upon conversion of the Notes, if any, have not been and will not be registered under the Securities Act or the securities laws of any other jurisdiction, and the Notes and any such shares may not be offered or sold in the United States absent registration or an applicable exemption from such registration requirements. Any offer of the Notes will be made only by means of a private offering memorandum.

This press release does not constitute an offer to sell or the solicitation of an offer to buy the Notes or any other securities, nor shall there be any offer, solicitation or sale of the Notes or any other securities (including the shares of Karyopharm’s common stock issuable upon conversion of the Notes, if any) in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful

Horizon Pharma plc to Release Third-Quarter 2018 Financial Results and Host Webcast on Nov. 7, 2018

On October 10, 2018 Horizon Pharma plc (Nasdaq: HZNP) reported that its third-quarter financial results will be released on Wednesday, Nov. 7, 2018 (Press release, Horizon Pharma, OCT 10, 2018, View Source [SID1234529838]). Following the announcement, Horizon’s management will host a live webcast at 8 a.m. Eastern Time to review the Company’s financial and operating results.

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The live webcast and replay may be accessed at View Source Please connect to the Company’s website at least 15 minutes before the live webcast to ensure adequate time for any software download that may be needed to access the webcast.

VACCIBODY UPDATES ON CANCER NEOANTIGEN PHASE I/IIA CLINICAL TRIAL: FIRST 10 PATIENTS ENROLLED, AND VACCINATIONS STARTED.

On October 10, 2018 Vaccibody AS, a clinical stage immunotherapy company focused on developing personalized neoantigen cancer vaccines to target solid tumors, reported that the first 10 patients have been enrolled in its phase I/IIa cancer neoantigen vaccine trial and that vaccinations with VB10.NEO have started (Press release, Vaccibody, OCT 10, 2018, View Source [SID1234529872]). The trial is planned to enroll up to 40 patients with locally advanced or metastatic melanoma, non-small cell lung carcinoma, clear renal cell carcinoma as well as urothelial cancer or squamous cell carcinoma of the head and neck. The VB10.NEO vaccine is given in combination with standard of care checkpoint inhibitors.

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Mads Axelsen, MD, Chief Medical Officer in Vaccibody, said "We are very pleased with the enrolment in the neoantigen trial and with the interest we are experiencing from clinical investigator and from patients. To that end I would like to thank the experienced cancer experts and investigators in this trial namely Prof. Jürgen Krauss from Heidelberg, Prof. Angela Krackhardt from Munich and Prof. Elke Jäger from Frankfurt. Together with their dedicated teams they are doing an outstanding job with the neoantigen trial"

Onconova Therapeutics To Present Update At The 2018 BIO Investor Forum In San Francisco

On October 10, 2018 Onconova Therapeutics, Inc. (NASDAQ:ONTX), a Phase 3-stage biopharmaceutical company focused on discovering and developing novel products to treat cancer, with a primary focus on myelodysplastic syndromes (MDS), reported that the Company will be presenting at the BIO Investor Forum, October 17-18, 2018, at the Westin St. Francis Hotel in San Francisco (Press release, Onconova, OCT 10, 2018, View Source [SID1234529839]). Ramesh Kumar, CEO, will present at the conference and meet with investors.

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Presentation details
Date/Time: Thursday, October 18th at 11:00 AM
Venue: The Westin St. Francis, San Francisco
Presenter: Ramesh Kumar, CEO

Constellation Pharmaceuticals Enhances and Expands Phase 2 MANIFEST Study of CPI-0610 in Myelofibrosis

On October 10, 2018 Constellation Pharmaceuticals, Inc. (Nasdaq: CNST), a clinical-stage biopharmaceutical company using its expertise in epigenetics to discover and develop novel therapeutics, reported several planned updates to the Phase 2 portion of its ongoing MANIFEST study, an open-label Phase 1/2 clinical trial of its BET inhibitor CPI-0610 in MF (Press release, Constellation Pharmaceuticals, OCT 10, 2018, View Source [SID1234530620]).

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MANIFEST is evaluating CPI-0610, either as a monotherapy or in combination with ruxolitinib, in patients with MF who are refractory or intolerant or have relapsed or lost response to the standard of care. Based on encouraging preliminary data in this trial, Constellation is amending the design of each second-line cohort to stratify all patients enrolled in the study based on transfusion dependence status. In addition, the Company is amending the design of MANIFEST to include a third cohort designed to evaluate treatment with CPI-0610 in combination with ruxolitinib as a first-line therapy in JAK 1/2-inhibitor-naïve MF patients.

The Company made these updates based on the unmet medical need for disease-modifying therapies in myelofibrosis, especially among patients requiring red-blood-cell transfusions. The changes are intended to enhance the clinical trial design by providing additional measures of potential clinical benefit and to expand the potential addressable patient population for CPI-0610.

"We are encouraged by the preliminary data from MANIFEST, which may indicate synergistic and disease-modifying effects of CPI-0610 in myelofibrosis," said Adrian Senderowicz, Senior Vice President and Chief Medical Officer of Constellation Pharmaceuticals. "We are enhancing the study’s design to better measure these potential effects. Among the key goals of MANIFEST are identifying the most appropriate endpoints and patient populations for future pivotal studies. We continue to look forward to determining proof of concept for CPI-0610 in MF by mid-2019."

MANIFEST Enhancements

The Phase 2 proof-of-concept portion of MANIFEST in a second-line setting is designed to study the anti-tumor activity and safety of the BET inhibitor CPI-0610 in treatment of patients with MF as a monotherapy and in combination with the JAK-1/2 inhibitor ruxolitinib. This portion of the study had been expected to enroll 70 patients (35 on monotherapy and 35 on combination therapy) to evaluate safety, pharmacokinetics, reduction in spleen volume, and patient-reported symptom improvement in all enrolled patients, as well as improvements in red-blood-cell transfusion independence rate in patients who were transfusion-dependent at baseline. Preliminary data from this trial demonstrated spleen volume reduction, symptom improvement, and positive hemoglobin effects, which Constellation believes may be the result of improved hematopoiesis. In addition, as Constellation reported previously, one of four patients treated with CPI-0610 was transfusion-dependent at baseline and later converted to transfusion independence.

As a result of this positive preliminary hematological data, all enrolled patients in both the combination and monotherapy arms will now be stratified by transfusion dependence status, with each cohort expected to enroll up to 16 transfusion-dependent patients and up to 25 non-transfusion-dependent patients. Proof of concept in these cohorts will be based on conversion to transfusion independence and other factors in transfusion-dependent patients; and by reduction in spleen volume, patient-reported symptom improvement, and other factors in non-transfusion-dependent patients.

In addition, Constellation is adding a third cohort to this trial, which will evaluate treatment with CPI-0610 in combination with ruxolitinib as first-line therapy in up to 43 JAK 1/2-inhibitor-naïve MF patients. This cohort will only enroll anemic patients. Constellation’s current plan for a potential pivotal trial of CPI-0610 as a first-line treatment would be to enroll all-comers. Proof of concept for this cohort will be measured by reduction in spleen volume, patient-reported symptom improvement, and other factors.

The Company expects to update this protocol change at View Source under study ID NCT02158858 in the near future.

Conference Call/Corporate Presentation

Constellation’s CEO Jigar Raythatha and CMO Adrian Senderowicz will host a conference call to discuss this protocol change in greater detail at 8:30 AM EDT on Thursday, October 11. To participate in the conference call, please dial (877) 473-2077 (US) or +1(661) 378-9662 (international) and refer to conference ID 4165317. A live webcast will be available in the investor section of the company’s website. The webcast will be archived for 60 days following the call. Constellation has posted an updated version of its corporate presentation in the investor section of the company’s website.