On December 5, 2022 Acorda Therapeutics, Inc. (Nasdaq: ACOR) reported that it made a cash interest payment of approximately $6.2 million due on December 1, 2022 under its Convertible Senior Secured Notes Indenture (Press release, Acorda Therapeutics, DEC 5, 2022, View Source [SID1234624773]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Acorda may elect to make interest payments under the Indenture in cash or shares of the Company’s common stock. The Company made the interest payment using cash that was placed in escrow when the Notes were issued, which is reported on the Company’s balance sheet as restricted cash. By making this interest payment in cash, the Company has ensured that there was no dilution to shareholders.

On December 5, 2022 Nkarta, Inc. (Nasdaq: NKTX), a biopharmaceutical company developing engineered natural killer cell therapies to treat cancer, reported positive updated data from its Phase 1 dose escalation study of NKX019 as monotherapy to treat patients with relapsed or refractory (r/r) non-Hodgkin lymphoma (NHL) (Press release, Nkarta, DEC 5, 2022, View Source [SID1234624771]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Seven of ten patients treated at the higher dose levels in a three-dose regimen showed a complete response (70% CR), including two patients with aggressive large B cell lymphoma (LBCL), one patient with mantle cell lymphoma (MCL), and one patient with marginal zone lymphoma (MZL). No dose limiting toxicity, neurotoxicity / ICANS, graft versus host disease (GvHD), or >Gr3 cytokine release syndrome (CRS) were observed in the study.

"NKX019 continues to demonstrate impressive single-agent activity, preliminary durability and an encouraging safety profile as an off-the-shelf, on-demand cell therapy for heavily pre-treated patients with NHL," said Paul J. Hastings, President and CEO of Nkarta. "Based on this initial success, we recently opened dose expansion cohorts to explore combination and single-agent regimens in patients with LBCL, an especially aggressive form of lymphoma, and to address the large unmet need in patients who have received prior autologous CAR T therapy. We remain committed to improved access for patients through the integration of cell therapy into the broader outpatient setting."

Nkarta plans to provide updates from the NKX019 program, including data from the dose expansion cohorts, in 2023.

Evaluating NKX019 in r/r B cell malignancies
NKX019 is an allogeneic, cryopreserved, off-the-shelf cancer immunotherapy candidate that uses NK cells engineered to target the B-cell antigen CD19, a clinically validated target for B-cell cancer therapies. The NKX019 Phase 1 study is evaluating the safety and anti-tumor activity of NKX019 as a multi-dose, multi-cycle therapy in patients with r/r B cell malignancies.

As of November 28, 2022, 19 patients were enrolled and dosed. Fourteen patients entered the study with a diagnosis of non-Hodgkin lymphoma (NHL), 7 of which were aggressive large B cell lymphoma (LBCL). Patients had received a median of 4 prior lines of therapy (range of 2 to 10). To date, enrollment has included patients with aggressive disease characteristics and extensive lesions throughout the body. Patients were enrolled at clinical trial sites in Australia (13) and the United States (6).

"Autologous CAR T cell therapy has undeniably changed the NHL treatment landscape, but the possibility of severe toxicity and the limited access of these therapies leave many potentially eligible patients without a cellular therapy option," said Michael Dickinson, M.D., Lead, Aggressive Lymphoma disease group, Clinical Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, and investigator in the NKX019 trial. "In the data so far, NKX019 has shown encouraging anti-tumor activity, including in patients with aggressive histologies, who are the patients who are most in need."

Safety in NKX019
NKX019 was well tolerated. No ICANS, GvHD, or >Gr3 CRS were observed in the study. No dose-limiting toxicities were observed. Five patients developed fever within 8 hours of NKX019 infusion, and each resolved within 24 hours. 2 of the 5 patients were assessed to have infusion-related reactions, 2 patients were assessed to have CRS, despite the rapid onset and rapid resolution not common in CRS, and one patient had both entities described in two separate cycles. The most common higher-grade adverse events were myelosuppression – a condition resulting in fewer red blood cells, white blood cells and platelets, which is common in this patient population post lymphodepletion. (See table 1.) The emerging safety profile of NKX019 is positively differentiated from those of many cell therapies.

NXK019 Safety (Table 1)

Grade 3/4 AEs in > 1 subject​​ Total (N=19)​​
Subjects with any ≥ Grade 3 AEs ​16 (84%)
Neutrophil count decreased 12 (63%)
Platelet count decreased 8 (42%)​
Febrile neutropenia ​ 5 (26%)​
Anemia​ 4 (21%)​
WBC count decreased 3 (16%)
Lymphocyte count decreased 2 (11%)
Treatment emergent adverse events regardless of relationship based on interim data from open clinical database as of 28 November 2022 ​

Clinical Activity in NXK019
Nineteen patients who received NKX019 were assessed (See table 2). In the two highest dose cohorts (1 B cells x 3 and 1.5 B cells x 3), 8 out of 10 patients with NHL achieved an objective response (80% ORR) and 7 out of 10 achieved a complete response (70% CR). 5 of 6 patients with NHL in the cohort receiving 3 doses of 1 billion cells achieved a response (83% ORR), and 4 of 6 achieved a complete response (67% CR rate). 3 of 4 patients with NHL in the cohort receiving 3 doses of 1.5 billion cells achieved a response (75% ORR) and a complete response (75% CR). For all cohorts in the dose finding portion (300 M cells x 3, 1 B cells x 3, and 1.5 B cells x 3), 10 of 14 patients with NHL achieved an objective response (71% ORR) and 8 of 14 achieved a complete response (57% CR). 3 patients with ALL and 2 patients with CLL were treated, with no response observed.

NKX019 Clinical Activity (Table 2)

300 M cells x 3 1 B cells x 3 1.5 B cells x 3
ORR (CR, PR) CR ORR (CR, PR) CR ORR (CR, PR) CR
All NHL 2/4 (50%) 1/4 (25%) 5/6 (83%) 4/6 (67%) 3/4 (75%) 3/4 (75%)
LBCL# 1/3 0/3 1/2 1/2 1/2 1/2
MCL - - 1/1 1/1 - -
FL 1/1 1/1 2/2 1/2 2/2 2/2
MZL - - 1/1 1/1 - -

Leukemia
ALL 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/2 (0%) - -
CLL - - - - 0/2 [1/2 SD] 0/2

#LBCL includes DLBCL and FL3b
ALL: acute lymphoblastic leukemia; CLL: chronic lymphocytic leukemia; CR: complete response; FL: follicular lymphoma; LBCL: large B-cell lymphoma; MCL: mantle cell lymphoma; MZL: marginal zone lymphoma; NHL: non-Hodgkin lymphoma; ORR: overall response rate; PR: partial response

About the NKX019 Clinical Trial
NKX019 is an allogeneic, cryopreserved, off-the-shelf cancer immunotherapy candidate that uses natural killer (NK) cells engineered to target the B-cell antigen CD19, a clinically validated target for B-cell cancer therapies. The dose-finding portion of the NKX019 Phase 1 study evaluates the safety and anti-tumor activity of NKX019 as a multi-dose, multi-cycle monotherapy following lymphodepletion in patients with r/r B-cell malignancies. Patients must have received at least two prior therapies. Patients that received prior autologous CAR-T therapy were not eligible.

Patients in the NKX019 trial received a cycle of treatment consisting of lymphodepletion with 3 days of fludarabine and cyclophosphamide followed by NKX019 cells in a three-dose regimen where cells were given on Days 0, 7, and 14. Patients received doses of 300 million, 1 billion, or 1.5 billion cells three times in a cycle. Based on tumor response and tolerability assessment, patients are eligible to receive additional treatment cycles, including patients with progressive disease to observe whether NKX019 can reverse progression. Disease assessment was performed by investigator review according to the 2014 Lugano response criteria for patients with NHL and NCCN response criteria for patients with ALL.

The dose-expansion portion of the Phase 1 clinical trial of NKX019 will investigate NKX019 as combination therapy with rituximab, an anti-CD20 monoclonal antibody, in patients with r/r non-Hodgkin lymphoma, as well as NKX019 as monotherapy in patients with large B-cell lymphoma (LBCL) who previously received autologous CD19 CAR T-cell therapy. The dose expansion will also further investigate NKX019 as monotherapy in patients with LBCL who have not previously received autologous CD19 CAR T-cell therapy.

Conference Call Information
Nkarta management will discuss the NKX019 results on Monday, December 5, 2022, at 8:00 a.m. ET. To access the live webcast, please register online on the Investors section of Nkarta’s website: View Source An archived webcast and accompanying slides will be available on the Company’s website approximately two hours after the event.

About NKX019
NKX019 is an allogeneic, cryopreserved, off-the-shelf cancer immunotherapy candidate that uses natural killer (NK) cells derived from the peripheral blood of healthy adult donors. It is engineered with a humanized CD19-directed CAR for enhanced tumor cell targeting and a proprietary, membrane-bound form of interleukin-15 (IL-15) for greater persistence and activity without exogenous cytokine support. CD19 is a biomarker for normal and malignant B cells, and it is a validated target for B cell cancer therapies. To learn more about the NKX019 clinical trial in adults with advanced B cell malignancies, please visit ClinicalTrials.gov.

On December 5, 2022 Kintara Therapeutics presented its corporate presentation (Presentation, Kintara Therapeutics, DEC 5, 2022, View Source [SID1234624769]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

On December 5, 2022 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported that it has entered into a securities purchase agreement with certain institutional investors for a private placement that is expected to result in gross proceeds of approximately $165 million before deducting any offering related expenses (Press release, Karyopharm, DEC 5, 2022, View Source [SID1234624768]). The private placement was led by Avidity Partners, with participation by existing stockholders and new investors including Adage Capital Partners LP, Armistice Capital, Healthcor Management LP, Heights Capital Management, Marshall Wace, Rubric Capital Management LP, SilverArc Capital and Surveyor Capital (a Citadel company).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In the private placement, the Company agreed to sell 31,791,908 shares of common stock at a price of $5.19 per share and to issue accompanying warrants to purchase 9,537,563 shares of common stock with an exercise price of $6.36 per share. The warrants will be exercisable at any time after they are issued and prior to the fifth anniversary of the closing date. The private placement is expected to close on or about December 7, 2022, subject to the satisfaction of customary closing conditions. The private placement is being conducted in accordance with applicable Nasdaq rules and was priced to satisfy the "Minimum Price" requirement (as defined in the Nasdaq rules).

Jefferies, Piper Sandler and Barclays are acting as lead placement agents. Baird and H.C. Wainwright & Co. are acting as co-placement agents in the private placement.

Karyopharm expects to use the proceeds from the private placement, together with its existing cash, cash equivalents and investments, for the advancement of the Company’s clinical development programs with selinexor and eltanexor as well as for working capital and other general corporate purposes.

The securities to be sold in the private placement have not been registered under the Securities Act of 1933, as amended (Securities Act), or any state or other applicable jurisdiction’s securities laws, and may not be offered or sold in the United States absent registration or an applicable exemption from the registration requirements of the Securities Act and applicable state or other jurisdictions’ securities laws. The Company has agreed to file a registration statement with the U.S. Securities and Exchange Commission registering the resale of the shares of common stock and the shares of common stock issuable upon the exercise of the warrants issued in the private placement no later than the 30th day after the closing of the private placement.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any offer, solicitation or sale of these securities in any jurisdiction in which such offer, solicitation or sale would be unlawful. Any offering of the securities under the resale registration statement will only be made by means of a prospectus.

On December 5, 2022 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported that it will host a webcast to discuss the updated results from the Phase 1 open-label, dose-escalation study evaluating selinexor in combination with ruxolitinib in patients with treatment-naïve myelofibrosis at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) 2022 Annual Meeting and Exposition (Press release, Karyopharm, DEC 5, 2022, View Source [SID1234624767]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The webcast will feature updates from Dr. Haris Ali, Associate Professor, MPN Section Leader for Leukemia Division, City of Hope Comprehensive Cancer Center, and Dr. Srdan Verstovsek, Director of Clinical Research for Myeloproliferative Neoplasms at MD Anderson Cancer Center. Drs. Ali and Verstovsek will discuss the updated data on selinexor in combination with ruxolitinib as well as the current treatment landscape and unmet medical need in treating patients with myelofibrosis, respectively. The event will be held on Monday, December 12, 2022, from 8:30 a.m. – 9:30 a.m. ET (7:30 a.m. – 8:30 a.m. CT).

To access the event, the live audio webcast and slides will be available under "Events & Presentations" in the Investor section of the Company’s website, View Source An archived webcast will be available on the Company’s website following the event.

Details for Karyopharm’s presence at ASH (Free ASH Whitepaper) 2022 are as follows:

Poster Presentations, Online Publication and Industry Theater

Title: A Phase 1, Open-Label, Dose-Escalation Study of Selinexor Plus Ruxolitinib in Patients with Treatment-Naïve Myelofibrosis
Presenter: Dr. Ali, City of Hope Comprehensive Cancer Center
Abstract #: 1734
Session Type: Poster Presentation
Session: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Poster I
Date and Time: Saturday, December 10, 2022, 5:30 PM – 7:30 PM CT

Title: Once Weekly Selinexor, Carfilzomib and Dexamethasone (XKd) in Triple Class Refractory Multiple Myeloma
Presenter: Dr. Schiller, David Geffen School of Medicine at UCLA
Abstract #: 4516
Session Type: Poster Presentation
Session: 652. Multiple Myeloma and Plasma Cell Dyscrasias: Clinical and Epidemiological: Poster III
Date and Time: Monday, December 12, 2022, 6:00 PM – 8:00 PM CT

Online Publication

Title: Real-World Safety and Effectiveness of Selinexor-Based Regimens in Patients with Relapsed or Refractory Multiple Myeloma and Dialysis-Dependent Renal Impairment
Presenter: Dr. Niblock, Karyopharm Therapeutics
Abstract #: 5773
Session Type: Online publication
Date and Time: Available in the November supplemental issue of Blood

Industry Theater

Title: Investigating Nuclear Transport Inhibition in Myelofibrosis (MF) and Myelodysplastic Neoplasms (MDS)
Presenter: Dr. Rangwala, Karyopharm Therapeutics
Session Type: Industry Theater
Location: Hall J – Theater 5
Date and Time: Sunday, December 11, 2022, 11:30 AM – 12:30 PM CT

Please note, the industry theater is not an official event of the 64th ASH (Free ASH Whitepaper) Annual Meeting & Exposition. This event is not sponsored or endorsed by ASH (Free ASH Whitepaper) and it is not CME-accredited.

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.