On November 3, 2022 Corcept Therapeutics Incorporated (NASDAQ: CORT), a commercial-stage company engaged in the discovery and development of medications to treat severe endocrine, oncologic, metabolic and neurological disorders by modulating the effects of the hormone cortisol, reported its results for the quarter ended September 30, 2022 (Press release, Corcept Therapeutics, NOV 3, 2022, View Source [SID1234622970]).

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Financial Results

Revenue of $101.7 million, compared to $96.1 million in third quarter 2021
Tightened 2022 revenue guidance of $400 – $410 million
Diluted net income per common share of $0.30, compared to $0.24 in third quarter 2021
Cash and investments of $401.2 million, compared to $382.0 million at June 30, 2022
Corcept’s third quarter 2022 revenue was $101.7 million, compared to $96.1 million in the third quarter of 2021. Third quarter operating expenses were $69.8 million, compared to $59.9 million in the third quarter of 2021, due to increased clinical trial and sales and marketing activities and expenses to support the expansion of our clinical development and commercial teams. Net income was $34.6 million in the third quarter of 2022, compared to $30.5 million in the third quarter of 2021.

Cash and investments of $401.2 million at September 30, 2022 reflects the acquisition in the third quarter of $15.5 million of Corcept common stock in connection with the exercise of employee stock options and vesting of restricted stock grants.

"Diagnosing and treating patients with a complex disease such as Cushing’s syndrome requires frequent in-person contact with physicians. Our revenue in the third quarter was affected by fewer than expected in-person interactions as many physician practices have not returned to pre-pandemic patterns of activity. To reflect this near-term challenge, we are tightening our 2022 revenue guidance to $400 to $410 million," said Joseph K. Belanoff, MD, Corcept’s Chief Executive Officer. "We remain extremely optimistic about the present and the future of our Cushing’s syndrome business. Korlym is an excellent treatment for patients with Cushing’s syndrome and there are many eligible patients who have yet to receive it. We are making substantial investments to improve the screening and treatment of these patients and we are confident that these initiatives will contribute to our results in the coming quarters."

Clinical Development

"Our clinical trials continue to advance and generate data supporting cortisol modulation’s broad therapeutic potential," added Dr. Belanoff. "We are very excited about our most recently initiated studies: ROSELLA, our confirmatory Phase 3 trial in platinum-resistant ovarian cancer; and DAZALS, our Phase 2 trial in ALS. We are also looking forward to important readouts from our two Phase 2 trials in antipsychotic-induced weight gain by the end of this year."

Oncology

Enrollment continues in ROSELLA – 360-patient pivotal Phase 3 trial of relacorilant plus nab-paclitaxel in patients with recurrent, platinum-resistant ovarian cancer
Enrollment continues in open-label, Phase 1b trial of relacorilant plus
pembrolizumab in patients with adrenal cancer with cortisol excess
Randomized, placebo-controlled Phase 2 trial of relacorilant plus enzalutamide in patients with prostate cancer to begin next year in collaboration with the University of Chicago
"We and our investigators are excited that ROSELLA is active and enrolling patients," said Bill Guyer, PharmD, Corcept’s Chief Development Officer. "Our goal in this trial is to replicate the positive results of our successful Phase 2 study, which demonstrated improvements in progression-free survival, duration of response and overall survival, all without increasing side effect burden. Women with platinum-resistant ovarian cancer do not have good treatment options and relacorilant plus nab-paclitaxel has the potential to become a new standard of care."

Amyotrophic Lateral Sclerosis (ALS)

Enrollment continues in DAZALS – 198-patient, randomized, double-blind, placebo-controlled Phase 2 trial of dazucorilant in patients with ALS
"ALS, also known as Lou Gehrig’s disease, is a devastating neuromuscular illness with an urgent need for better treatment," said Dr. Guyer. "Dazucorilant showed great promise in animal models of ALS – improving motor performance and reducing neuroinflammation and muscular atrophy. We are excited to initiate this important study in collaboration with TRICALS, the leading ALS academic consortium in Europe, to investigate dazucorilant’s potential to significantly improve the lives of patients with ALS."

Metabolic Diseases

Enrollment completed in GRATITUDE and GRATITUDE II – two double-blind, placebo-controlled Phase 2 trials of miricorilant to reverse recent and long-standing antipsychotic-induced weight gain (AIWG) – data from both trials expected this quarter
Enrollment continues in Phase 1b dose-finding trial of miricorilant in patients
with presumed non-alcoholic steatohepatitis (NASH) – data expected in the first half of 2023
"We expect our double-blind, placebo-controlled GRATITUDE and GRATITUDE II trials in patients with AIWG to build on the positive data from our Phase 1 studies," said Dr. Guyer. "There is a substantial opportunity to improve the medical care of these patients as weight gain and other adverse metabolic effects caused by antipsychotic medications dissuade many patients from adhering to their treatment regimen, pose serious health risks and reduce the life expectancy of millions of patients."

"The goal of our Phase 1b dose-finding study in patients with NASH is to identify a dosing regimen that captures the unprecedented rapidity and magnitude of liver fat reduction observed in our prior study without causing excessive liver irritation," added Dr. Guyer.

Cushing’s Syndrome

Enrollment continues in Phase 3 GRACE trial of relacorilant as a treatment for patients with all etiologies of Cushing’s syndrome – new drug application (NDA) submission expected
in second half 2023
Enrollment continues in Phase 3 GRADIENT trial of relacorilant as a treatment for patients
with Cushing’s syndrome caused by adrenal adenomas
"We advanced relacorilant to Phase 3 in Cushing’s syndrome based on its extremely promising Phase 2 efficacy and safety data. We expect our GRACE trial to serve as the basis for relacorilant’s NDA in Cushing’s syndrome, which we plan to submit in the second half of 2023," said Dr. Guyer. "The Phase 3 GRADIENT trial will produce valuable data about an etiology of Cushing’s syndrome that has not been subject to rigorous, controlled study, but affects many patients."

Conference Call

We will hold a conference call on November 3, 2022, at 5:00 p.m. Eastern Time (2:00 p.m. Pacific Time). Participants must register in advance of the conference call by clicking here. Upon registering, each participant will receive a dial-in number, and a unique access PIN. Each access PIN will accommodate one caller. Additionally, a listen-only webcast will be available by clicking here. A replay of the call will be available on the Investors / Events tab of www.corcept.com.

Hypercortisolism

Hypercortisolism, often referred to as Cushing’s syndrome, is caused by excessive activity of the hormone cortisol. Endogenous Cushing’s syndrome is an orphan disease that most often affects adults aged 20-50. In the United States, an estimated 20,000 patients have Cushing’s syndrome, with about 3,000 new patients diagnosed each year. Symptoms vary, but most patients experience one or more of the following manifestations: high blood sugar, diabetes, high blood pressure, upper-body obesity, rounded face, increased fat around the neck, thinning arms and legs, severe fatigue and weak muscles. Irritability, anxiety, cognitive disturbances and depression are also common. Hypercortisolism can affect every organ system and can be lethal if not treated effectively. Corcept holds patents directed to the composition of relacorilant and the use of cortisol modulators, including Korlym, in the treatment of patients with hypercortisolism.

On November 3, 2022 Cytokinetics, Incorporated (Nasdaq: CYTK) reported financial results for the third quarter of 2022 (Press release, Cytokinetics, NOV 3, 2022, View Source [SID1234622969]). Net loss for the third quarter was $142.3 million, or $1.52 per share, compared to net loss for the third quarter of 2021 of $76.1 million, or $0.95 per share. Cash, cash equivalents and investments totaled $896.2 million at September 30, 2022.

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"During the third quarter, we continued to execute towards our potential transformation to commercialization with expansion of teams and readiness activities in preparation for our upcoming FDA Advisory Committee meeting and the potential launch of omecamtiv mecarbil," said Robert I. Blum, Cytokinetics’ President and Chief Executive Officer. "At the same time, the development program for aficamten is proceeding with continued conduct of Cohort 4 of REDWOOD-HCM and SEQUOIA-HCM, alongside start up activities for our second Phase 3 clinical trial of aficamten. We also are continuing COURAGE-ALS following its first interim analysis marking progress aligned with our commitment to ALS. We have entered the fourth quarter with a strong balance sheet ahead of key corporate milestones."

Q3 and Recent Highlights

Cardiac Muscle Programs

omecamtiv mecarbil (cardiac myosin activator)

Engaged in further interactions with the U.S. Food and Drug Administration (FDA) related to our New Drug Application (NDA) for omecamtiv mecarbil. Continued discussions with FDA regarding matters related to substantial evidence of efficacy, benefit-risk, and dosing.

Conducted meetings with assigned rapporteurs to discuss the planned submission of a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA).

Continued commercial preparations for the potential U.S. launch of omecamtiv mecarbil including convening meetings with national and regional payers, advancing wholesaler agreements for distribution, finalizing third party logistics agreement, completing strategic sourcing of drug substance and drug product contract manufacturing organizations, continuing development of patient services hub, and beginning the final wave of hiring for sales force leaders.

Expanded the headquarters- and field-based medical affairs team, continued support of independent medical education activities at medical conferences, and initiated planning for our Medical Contact Center.

Launched "The Heart of Contractility," a disease state education campaign for healthcare providers to build awareness of worsening heart failure and the importance of contractility.
aficamten (cardiac myosin inhibitor)

Continued clinical trial site activation and enrollment of patients with obstructive HCM in SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM), our first Phase 3 trial of aficamten, with 70 sites now enrolling in the U.S. and Europe.

Completed screening for patients with non-obstructive HCM to enroll in Cohort 4 of REDWOOD-HCM (Randomized Evaluation of Dosing With CK-274 in Obstructive Outflow Disease in HCM).

Renamed the open-label extension clinical study of aficamten in patients with hypertrophic cardiomyopathy (HCM), previously known as REDWOOD-HCM OLE (Randomized Evaluation of Dosing With CK-274 in Obstructive Outflow Disease in HCM Open Label Extension) to FOREST-HCM (Five-Year, Open-Label, Research Evaluation of Sustained Treatment with Aficamten in HCM) to reflect the entry of patients from additional clinical trials of aficamten including SEQUOIA-HCM.

Presented data from FOREST-HCM (previously known as REDWOOD-HCM OLE) at the Heart Failure Society of America (HFSA) Annual Scientific Meeting showing that treatment with aficamten was associated with substantial and significant symptom improvements as measured by the change in Kansas City Cardiomyopathy Questionnaire (KCCQ) scores.

Presented data from FOREST-HCM at the 2022 HCM Society Scientific Sessions demonstrating in patients treated with aficamten the successful reduction or withdrawal of standard of care therapies.

Published a manuscript entitled "A Phase 1 Dose-Escalation Study of the Cardiac Myosin Inhibitor Aficamten in Healthy Participants" in JACC: Basic to Translational Science.
Skeletal Muscle Program

reldesemtiv (fast skeletal muscle troponin activator (FSTA))

Announced that the Data Monitoring Committee (DMC) for COURAGE-ALS (Clinical Outcomes Using Reldesemtiv on ALSFRS-R in a Global Evaluation in ALS) convened to review unblinded data from the clinical trial and recommended that conduct of the Phase 3 trial continue.
Pre-Clinical Development and Ongoing Research

Continued to advance new muscle directed compounds and conduct IND-enabling studies with the expectation of our potentially moving 1-2 drug candidates into clinical development in the next year.

Continued research activities directed to our other muscle biology research programs.
Corporate

Raised $523.6 million in net proceeds from a 3.50% convertible senior notes offering (due 2027), after deducting underwriters’ discounts and transaction fees, and before repurchasing approximately $117 million of previously outstanding 4.00% convertible senior notes (due 2026).

Announced a new release of the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database updated with clinical data from Cytokinetics’ completed clinical trials in ALS.

Announced a call for proposals for the fifth annual Cytokinetics Communications Grant program. The program awards five grants worth $20,000 each to patient advocacy organizations serving the ALS, heart failure, and HCM communities, and is intended to help support increased capacity in communications and outreach.
Upcoming Corporate Milestones

Cardiac Muscle Programs

omecamtiv mecarbil (cardiac myosin activator)

Participate in Advisory Committee meeting to review the NDA for omecamtiv mecarbil on December 13, 2022.

Launch omecamtiv mecarbil in the U.S. subject to FDA approval in Q1 2023.

Submit Marketing Authorization Application (MAA) to the European Medicines Agency by the end of 2022.
aficamten (cardiac myosin inhibitor)

Continue enrolling patients with obstructive HCM in SEQUOIA-HCM through 1H 2023 with results expected in 2H 2023.

Complete enrolling patients with non-obstructive HCM in Cohort 4 of REDWOOD-HCM with data expected in 1H 2023.

Begin second Phase 3 clinical trial of aficamten in obstructive HCM in Q4 2022.
CK-3828136 (CK-136) (cardiac troponin activator)

Begin Phase 1 study of CK-136 in Q4 2022.
Skeletal Muscle Program

reldesemtiv (fast skeletal muscle troponin activator (FSTA))

Expect the Data Monitoring committee to conduct the second interim analysis from COURAGE-ALS in 1H 2023, which will assess for futility and allow for a fixed increase in total enrollment, if deemed necessary, to augment the statistical power of the trial.

Continue enrolling patients with ALS in COURAGE-ALS and expect to complete enrollment in 1H 2023.
Financials

Revenues for the three and nine months ended September 30, 2022 were $2.5 million and $92.6 million, respectively, compared to $5.4 million and $14.8 million for the corresponding period in 2021. The increase in revenues for the nine months ended September 30, 2022 was primarily due to the recognition of $87.0 million of deferred revenue for royalties on the net sales of products containing mavacamten as a result of the extinguishment of royalty obligations.

Research and development expenses for the three and nine months ended September 30, 2022 increased to $62.7 million and $165.8 million, respectively, compared to $48.4 million and $116.4 million for the same period in 2021. The changes were primarily due to increases in spending for clinical development activities for COURAGE-ALS and SEQUOIA-HCM, and for our other cardiac muscle inhibitor and early research programs.

General and administrative expenses for the three and nine months ended September 30, 2022 increased to $48.2 million and $124.0 million, respectively, from $26.2 million and $63.0 million for the same period in 2021 due primarily to higher outside services spending in anticipation of the potential commercial launch of omecamtiv mecarbil, and an increase in personnel related costs including stock-based compensation.

During the quarter, we recognized a loss of $22.2 million related to the conversion and partial settlement of our 2026 Convertible Notes.

Conference Call and Webcast Information

The conference call will be simultaneously webcast and can be accessed from the homepage and in the Investors & Media section of Cytokinetics’ website at www.cytokinetics.com. The live audio of the conference call can also be accessed by telephone by registering in advance at the following link: Cytokinetics Q3 2022 Earnings Conference Call. Upon registration, participants will receive a dial-in number and a unique passcode to access the call. An archived replay of the webcast will be available via Cytokinetics’ website for twelve months.

On November 3, 2022 Cellectis (the "Company") (Euronext Growth: ALCLS – NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, reported the release of two abstracts, which were accepted for presentation at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting taking place from December 10 to 13, 2022 (Press release, Cellectis, NOV 3, 2022, View Source [SID1234622968]).

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The Company will present, in an oral session on December 12, preliminary clinical data from its AMELI-01 clinical trial (evaluating UCART123) in patients with relapsed/refractory acute myeloid leukemia (r/r AML). Amsterdam University Medical Center (location VUmc), in collaboration with Cellectis, will also present, in a poster session on December 10, preclinical data supporting anti-tumor activity for Cellectis’ UCARTCS1 product candidate, which is being evaluated in clinical trial, MELANI-01, for patients with relapsed/refractory multiple myeloma (r/r MM).

"Cellectis is excited to share preliminary clinical data from our AMELI-01 clinical trial, evaluating UCART123 in patients with relapsed and/or refractory acute myeloid leukemia. This trial addresses a patient population with severe unmet medical needs and no additional therapeutic options. We hope our off-the-shelf approach through gene editing will serve as the next step in improving outcomes in patients with this disease," said Mark Frattini, M.D., Ph.D., Chief Medical Officer at Cellectis.

Cellectis’ oral presentation on AMELI-01:

AMELI-01 investigating UCART123 product candidate in r/r AML

The abstract includes preliminary clinical data from the Phase 1, open-label, dose-escalation trial, AMELI-01, in patients with r/r AML having received UCART123 following lymphodepletion (LD) with either fludarabine and cyclophosphamide (FC) or FC with alemtuzumab (FCA). The data show that adding alemtuzumab to the FC regimen was associated with improved LD and significantly higher UCART123 cell expansion, which correlated with improved activity.

UCART123 is a novel and genetically modified allogeneic T-cell product manufactured from healthy donor cells. Donor-derived T-cells are transduced using a lentiviral vector to express the anti-CD123 chimeric antigen receptor (CAR) and are further modified using Cellectis’ TALEN technology to disrupt the T-cell receptor alpha constant (TRAC) and CD52 genes to minimize risk of graft-vs-host disease (GvHD) and allow use of anti-CD52–directed therapy as a component of the LD regimen, respectively.

These data are encouraging and support the continued enrollment into the study.

Presentation Details:
Title: AMELI-01: A Phase I Trial of UCART123v1.2, an Anti-CD123 Allogeneic CAR-T Cell Product, in Adult Patients with Relapsed or Refractory (R/R) CD123+ Acute Myeloid Leukemia (AML)
Publication Number: 981
Presenter: David A. Sallman, MD, Moffitt Cancer Center, Department of Malignant Hematology, Tampa, FL
Session Name: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: Acute Leukemia and Hodgkin Lymphoma
Date, Time, Location: Monday, December 12, 2022; 5:00PM; Ernest N. Morial Convention Center, Hall E

Link to abstract, here.

Poster Presentation on UCARTCS1, in collaboration with Amsterdam UMC

The abstract includes preclinical data evaluating in vitro activity of UCARTCS1 against MM cell lines and bone marrow samples from MM patients, as well as in vivo activity in a MM mouse model. The potential impact of previous therapy and tumor characteristics on the in vitro efficacy of UCARTCS1 was also investigated.

The preclinical data that will be presented demonstrates anti-tumor activity in vitro and in vivo, supporting the potential benefit of UCARTCS1 first in-human study of, MELANI-01 a Phase 1, open-label, dose-escalation trial, for patients with r/r MM.

UCARTCS1 is a genetically modified allogeneic T-cell product manufactured from healthy donor cells. Donor-derived T-cells are transduced using a lentiviral vector to express the anti-CS1 CAR and are further modified using Cellectis’ TALEN gene editing technology to disrupt the T-cell receptor alpha constant (TRAC) and CS1 genes to minimize risk of graft-vs-host disease (GvHD) and avoid fratricide during production, respectively.

Presentation Details/Poster Abstract Session:

Title: Preclinical Activity of Allogeneic CS1-Specific CAR T-Cells (UCARTCS1) in Multiple Myeloma
Publication Number: 1833
Presenter: C.L.B.M. Korst, Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Hematology
Session Name: 651. Multiple Myeloma and Plasma Cell Dyscrasias: Basic and Translational: Poster I
Date, Time, Location: Saturday, December 10, 2022; 5:30 PM – 7:30 PM; Ernest N. Morial Convention Center, Hall D

On November 3, 2022 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported business highlights and financial results for the quarter ended September 30, 2022 (Press release, Karyopharm, NOV 3, 2022, View Source [SID1234622967]).

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"We had a highly productive third quarter executing against our key priorities which delivered strong growth in patient demand and product revenues. We also achieved an important milestone this quarter with the initiation of the pivotal Phase 3 study evaluating selinexor as a maintenance therapy in women with TP53 wild-type endometrial cancer and anticipate sharing topline results in 2024," said Richard Paulson, President and Chief Executive Officer of Karyopharm. "Today, our abstracts were released for the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, including encouraging data from the Phase 1 study evaluating selinexor in combination with ruxolitinib in patients with treatment-naïve myelofibrosis, which continues to demonstrate promising activity in key efficacy endpoints. We look forward to sharing further updated results from this study at the ASH (Free ASH Whitepaper) meeting in December."

Third Quarter 2022 and Recent Highlights

XPOVIO Commercial Performance

Achieved U.S. net product revenue for the third quarter of 2022 of $32.0 million, a 20% increase compared to the third quarter of 2021, driven by growth in new patient starts and refills.
XPOVIO continued its growth in the community setting, driven by the continued shift of XPOVIO into second to fourth lines of therapy and increasing confidence in the perception of the product.
Increased selinexor’s reach with the commercial launch of NEXPOVIO by the Company’s partner, Menarini Group, in Germany and Austria.
Research & Development (R&D) Highlights for Selinexor and Eltanexor

Initiated a global, randomized, double-blind Phase 3 study evaluating selinexor as maintenance therapy for patients with TP53 wild-type advanced or recurrent endometrial cancer. The study will utilize Foundation Medicine’s tissue-based next generation sequencing test to identify and enroll patients whose tumors are TP53 wild-type. Top-line results from the study are anticipated in 2024.
Results from the Phase 1 study evaluating selinexor in combination with ruxolitinib in patients with treatment-naïve myelofibrosis (NCT:04562389) have been accepted for poster presentation at the ASH (Free ASH Whitepaper) 2022 Annual Meeting. The data included in the abstract for ASH (Free ASH Whitepaper) 2022 were based on the Phase 1 portion of the Phase 1/2 study evaluating the safety and preliminary efficacy of once-weekly selinexor in combination with standard dose ruxolitinib in patients with treatment-naïve myelofibrosis (NCT04562389). As of July 2022, 19 patients had been assigned to either selinexor 40 mg or 60 mg, in combination with ruxolitinib 15/20 mg BID. 79% (11 out of 14) and 86% (6 out of 7) of efficacy evaluable patients demonstrated ≥35% reduction in spleen volume (SVR 35) at week 12 and at week 24, respectively. 69% (9 out of 13) of efficacy evaluable patients evidenced a ≥50% reduction (TSS50) at week 12 and 65% (11 out of 17) of transfusion-independent patients who had at least eight weeks of treatment maintained stable hemoglobin (± 2g/dL) or improved hemoglobin level (>2g/dL increase) at last follow up. The data observed across both 40mg and 60mg doses demonstrate a generally manageable side effect profile with no dose limiting toxicities at either dose level in the Phase 1a dose escalation with the most common adverse events (AEs) being nausea (58%), anemia (42%) and vomiting (42%), the majority of which were grades 1-2, and the most commonly reported grades 3-4 treatment-emergent AEs being thrombocytopenia (26%) and anemia (21%), which were reversible. Updated data from this study, including results from additional patients, will be presented at the ASH (Free ASH Whitepaper) meeting in December 2022.
The European Commission adopted the Committee for Orphan Medicinal Products opinion to designate selinexor as an orphan medicinal product for the treatment of myelofibrosis, and eltanexor as an orphan medicinal product for the treatment of myelodysplastic syndromes (MDS), in the European Union in October 2022 and July 2022, respectively.
FDA granted Fast Track Designation for the development program of eltanexor as monotherapy for the treatment of patients with relapsed or refractory intermediate, high-, or very high-risk MDS per IPSS-R in July 2022.
2022 Financial Guidance

Based on its current operating plans, Karyopharm is maintaining its guidance for the full year 2022:

Total revenue to be in the range of $155 million to $165 million.
XPOVIO net product revenue to be in the range of $120 million to $130 million.
Non-GAAP R&D and Selling, general and administrative (SG&A) expenses, excluding stock-based compensation expense, to be in the range of $250 million to $265 million.

Karyopharm has not reconciled the full year 2022 outlook for non-GAAP R&D and SG&A expenses to full year 2022 outlook for GAAP R&D and SG&A expenses because Karyopharm cannot reliably predict without unreasonable efforts the timing or amount of the factors that substantially contribute to the projection of stock compensation expense, which is excluded from the full year 2022 outlook for non-GAAP R&D and SG&A expenses.
The Company continues to expect that its existing cash, cash equivalents and investments, and the revenue it expects to generate from XPOVIO product sales, as well as revenue generated from its license agreements, will be sufficient to fund its planned operations into early 2024.
Third Quarter 2022 Financial Results

Total Revenue: Total revenue for the third quarter of 2022 was $36.1 million, down 4% compared to $37.7 million for the third quarter of 2021.

Net product revenue: Net product revenue for the third quarter of 2022 was $32.0 million, up 20% compared to $26.7 million for the third quarter of 2021.

License and other revenue: License and other revenue for the third quarter of 2022 was $4.1 million, compared to $11.0 million for the third quarter of 2021. The decrease was primarily attributable to the recognition of $9.8 million in milestone-related revenue from Antengene Therapeutics Limited (Antengene) in the third quarter of 2021, compared to $2.4 million in royalty revenue and $1.4 million in reimbursement revenue from Menarini recognized in the third quarter of 2022.

Cost of sales: Cost of sales for the third quarter of 2022 were $1.0 million, compared to $0.6 million for the third quarter of 2021. Cost of sales includes the costs of producing and distributing XPOVIO units sold and third-party royalties on net product revenue.

R&D expense: R&D expense for the third quarter of 2022 were $31.4 million, compared to $45.8 million for the third quarter of 2021. The decrease was primarily driven by the recognition of $7.4 million of costs in connection with the acquisition of certain assets from Neumedicines Inc. in the third quarter of 2021, for which there were no similar costs in 2022. Additionally, clinical trial and related costs decreased primarily due to the prioritization of the Company’s core programs in its clinical pipeline and the timing of the purchases of comparator drug used in clinical trials.

SG&A expense: SG&A expense for the third quarter of 2022 were $34.6 million, compared to $35.1 million for the third quarter of 2021.

Interest expense: Interest expense for the third quarter of 2022 was $6.1 million, compared to $8.0 million for the third quarter of 2021.

Net loss: Karyopharm reported a net loss of $36.3 million, or $0.45 per share, for the third quarter of 2022, compared to a net loss of $51.8 million, or $0.69 per share, for the third quarter of 2021. Net loss included non-cash stock-based compensation expense of $6.8 million and $7.4 million for the third quarters ended September 30, 2022 and 2021, respectively.

Cash position: Cash, cash equivalents, restricted cash and investments as of September 30, 2022, totaled $150.1 million, compared to $235.6 million as of December 31, 2021.

Non-GAAP Financial Information

Karyopharm uses a non-GAAP financial measure, non-GAAP R&D and SG&A expenses, to provide operating expense guidance. Non-GAAP R&D and SG&A expenses exclude stock-based compensation expense. Karyopharm believes this non-GAAP financial measure is useful to investors because it provides greater transparency regarding Karyopharm’s operating performance as it excludes non-cash stock compensation expense. This non-GAAP financial measure should not be considered a substitute or an alternative to GAAP R&D and SG&A expenses and should not be considered a measure of Karyopharm’s liquidity. Instead, non-GAAP R&D and SG&A expenses should only be used to supplement an understanding of Karyopharm’s operating results as reported under GAAP.

Conference Call Information

Karyopharm will host a conference call today, November 3, 2022, at 4:30 p.m. Eastern Time, to discuss the third quarter 2022 financial results and provide other business highlights. To access the conference call, please dial (888) 349-0102 (local) or (412) 902-4299 (international) at least 10 minutes prior to the start time and ask to be joined into the Karyopharm Therapeutics call. A live audio webcast of the call, along with accompanying 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 approximately two hours after the event.

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.

On November 3, 2022 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that it will webcast management participation as follows (Press release, Regeneron, NOV 3, 2022, View Source [SID1234622966]):

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Jefferies London Healthcare Conference at 3:15 p.m. GMT (10:15 a.m. ET) on Wednesday, November 16, 2022
5th Annual Evercore ISI HealthCONx Conference at 11:45 a.m. ET on Tuesday, November 29, 2022
Piper Sandler 34th Annual Healthcare Conference at 8:00 a.m. ET on Wednesday, November 30, 2022
The sessions may be accessed from the "Investors & Media" page of Regeneron’s website at View Source Replays of the webcasts will be archived on the Company’s website for at least 30 days.