On May 12, 2022 Salarius Pharmaceuticals, Inc. (Nasdaq: SLRX), a clinical-stage biopharmaceutical company developing cancer therapies for patients in need of new treatment options, reported important corporate events and its financial results for the first quarter ended March 31, 2022 (Press release, Salarius Pharmaceuticals, MAY 12, 2022, View Source [SID1234614476]).

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"We have high expectations for 2022 as we build on the progress achieved during the first quarter and recent weeks," stated David Arthur, CEO of Salarius Pharmaceuticals. "Recent highlights include our acquisition of an intellectual property portfolio, including the drug candidate SP-3164, which is now the foundation of our new drug development program focused on targeted protein degradation (TPD), and the subsequent completion of SP-3164’s pre-IND meeting process with the FDA. TPD is a fast-growing field of cancer drug research with significant potential to improve patient’s lives and a market potential estimated in the billions of dollars. Coupled with our existing clinical programs for seclidemstat, our most advanced cancer drug candidate, Salarius is now pursuing multiple drug development programs built around two exciting approaches to cancer drug development – protein inhibition and protein degradation."

Financial Highlights:
•Cash and cash equivalents totaled $24.2 million on March 31, 2022; $2.3 million direct offering with institutional investors closed on April 26, 2022; Estimated cash runway extends into 2023.
•For the three-month period ended March 31, 2022, net loss per common share, basic and diluted, of $0.13, compared to $0.06 for the same period in 2021
Recent Business and Corporate Highlights:
•2022 Annual Meeting of Stockholders announced for June 15, 2022; Company is seeking stockholder approval or authorization of four proposals and is encouraging stockholders to participate and vote their shares of Salarius Pharmaceuticals stock.

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•Advancing new TPD cancer drug development program built around an intellectual property portfolio acquired from DeuteRx LLC in January 2022. The lead development candidate is SP-3164 for which the company has:
◦Completed the FDA Pre-IND meeting process, which has informed planned IND-enabling studies and activities; and
◦Initiated preclinical studies to support the potential submission of an Investigational New Drug (IND) application with initial preclinical data anticipated in the second half of 2022 and potential for first clinical trial in 2023.
•Salarius continues its enrollment activities to advance clinical exploration of seclidemstat in the treatment of sarcomas, while MD Anderson Cancer Center is enrolling patients in the investigator-initiated trial exploring seclidemstat as a treatment for hematologic cancers.
◦Data updates expected in 2022 from both ongoing Phase 1/2 clinical trials.

"As both CEO and a stockholder of Salarius, I am excited about the upcoming value-building opportunities we expect to achieve" continued Mr. Arthur. "On June 15, the Company will hold its Annual Meeting of Stockholders, where Salarius is asking stockholders to vote on several proposals that we believe will augment these opportunities. All stockholders are encouraged to vote their shares through their brokerage website or through the proxy materials."

"We believe the combination of multiple drug development programs built around two exciting approaches to cancer drug development – protein inhibition and protein degradation – coupled with upcoming value-building opportunities will benefit both current and future stockholders" concluded Mr. Arthur.

Three-Month Financial Results:
For the three-month period ended March 31, 2022, Salarius’ reported net loss was $6.1 million, or $0.13 per basic and diluted share, compared to a net loss of $1.9 million, or $0.06 per basic and diluted share for the same period in 2021. The loss for the three-month period ended March 31, 2022, increased by $4.2 million compared to the same time span last year, primarily because the Company had higher research and development costs and no grant revenue in the current period.
Net cash used for operating activities during the three-month period ended March 31, 2022, totaled $3.5 million, compared to $2.7 million during the same span last year.
As of March 31, 2022, total cash, cash equivalents, and restricted cash were $24.2 million, compared to $36.6 million as of March 31, 2021. The decrease in cash was primarily driven by the Company’s continued spend on operating activities, especially research and development activities and less financing activities involved since Q1 2021. Current cash and cash equivalents are expected to fund our current planned operations into 2023.

Conference Call Information:
Salarius Pharmaceuticals will host a conference call and live audio webcast on Thursday, May 12, 2022, at 5:00 p.m. ET, to discuss its corporate and financial results for the first quarter 2021. Interested participants and investors may access the conference call by dialing either:

An audio webcast will be accessible via the Investors Events and Presentations section of the Company’s website View Source An archive of the webcast will remain available for 90 days beginning at approximately 6:00 p.m. ET on May 12, 2022.

On May 12, 2022 Veru Inc. (NASDAQ: VERU), a biopharmaceutical company focused on developing novel medicines for COVID-19 and other viral and ARDS-related diseases and for the management of breast and prostate cancers, reported financial results for its fiscal 2022 second quarter ended March 31, 2022 (Press release, Veru, MAY 12, 2022, View Source [SID1234614280]).

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Second Quarter Financial Summary: Fiscal 2022 vs Fiscal 2021

Total net revenues decreased 2% to $13.0 million from $13.3 million
US FC2 prescription net revenues climbed 12% to $11.6 million from $10.3 million
Gross profit rose 2% to $11.2 million from $10.9 million
Gross margin increased to 86% of net revenues from 82% of net revenues, a record high compared to any prior quarter
Operating loss was $11.8 million versus $1.5 million
Net loss was $14.2 million, or $0.18 per share, compared $2.8 million, or $0.04 per share
Year-to-Date Financial Summary: Fiscal 2022 vs Fiscal 2021

Total net revenues decreased 3% to $27.2 million from $28.0 million
US FC2 prescription net revenues climbed 19% to $23.2 million from $19.4 million
Gross profit rose 6% to $23.0 million from $21.7 million
Gross margin increased to 85% of net revenues from 78% of net revenues
Operating loss was $16.7 million compared with operating income of $17.7 million, which included an $18.4 million gain on the December 2020 sale of the PREBOOST business
Net loss was $20.6 million or $0.26 per diluted share compared with net income, which included the gain on the sale of the PREBOOST business, of $14.4 million or $0.18 per diluted share
Balance Sheet Information

Cash and cash equivalents were $112.0 million as of March 31, 2022 versus $122.4 million at September 30, 2021
Net accounts receivable of $8.1 million as of March 31, 2022 versus $8.8 million as of September 30, 2021
"Following a positive Phase 3 COVID-19 clinical study where sabizabulin treatment resulted in a clear clinical benefit by significantly reducing deaths, we met with FDA for a Pre-EUA meeting on May 10, 2022. FDA agreed that our development program had sufficient efficacy and safety data to support a request for EUA application. No additional efficacy or safety studies will be required," said Mitchell Steiner, M.D., Chairman, President and Chief Executive Officer of Veru Inc. "The Agency has been incredibly responsive, and we look forward to submitting a request for Emergency Use Authorization application as soon as possible. The high mortality rates observed in hospitalized moderate to severe COVID-19 patients in the placebo group underscores that this remains a high unmet medical need. We look forward to updating you as we advance sabizabulin to these high-risk patients."

Dr. Steiner added: "We continue to make great progress on our clinical programs for breast and prostate cancer. We now have 2 enrolling Phase 3 metastatic breast cancer clinical trials and one Phase 3 prostate cancer clinical trial. The Phase 3 COVID-19 clinical study is completed and met its primary endpoint. In our commercial business, we continue to see an increase in FC2 prescriptions and plan to launch ENTADFI soon. We also expect to have significant near-term revenue from sabizabulin for the treatment of hospitalized COVID-19 patients at high risk for ARDS, if EUA is granted by U.S. FDA."

Pharmaceutical Pipeline Highlights:

COVID-19 Program; Other Viral and ARDS-Related and Inflammatory-Related Diseases

Sabizabulin for the Treatment of Hospitalized COVID-19 Patients at High Risk for Acute Respiratory Distress Syndrome (ARDS) Phase 3 COVID-19 Clinical Study – Study Unanimously Halted by the Independent Data Monitoring Committee (IDMC) After a Planned Interim Analysis for Overwhelming Efficacy; Company Preparing an EUA Submission.

A randomized, double-blind, placebo-controlled global Phase 3 clinical trial was conducted in hospitalized patients with moderate to severe COVID-19 infection who were at high risk for ARDS and death. Patients were randomly assigned to receive sabizabulin 9mg or placebo once oral daily for up to 21 days in a 2:1 ratio. The primary endpoint was all-cause mortality up to day 60, and key secondary endpoints were days in intensive care unit (ICU), days on mechanical ventilation, and days in hospital.

A total of 204 patients underwent randomization (with 134 assigned to sabizabulin-treated group and 70 assigned to placebo-treated group). Both groups were allowed to receive standard of care. Baseline characteristics were similar in the two groups. The superiority of sabizabulin was demonstrated at the planned interim analysis conducted in the first 150 patients randomized into the study with 98 patients receiving sabizabulin and 52 patients received placebo. The IDMC unanimously voted to halt the Phase 3 because of overwhelming efficacy. Sabizabulin treatment resulted in a clinically meaningful and statistically significant 55.2% relative reduction in deaths compared to placebo in hospitalized patients with moderate to severe COVID-19 infection who were at high risk for ARDS and death with a lower incidence of adverse events and serious adverse events compared to placebo.

FDA agreed that the Phase 3 COVID-19 study is sufficient to support the efficacy portion of a request for EUA submission and for an NDA submission.

FDA also agreed that the current safety data available for sabizabulin is sufficient to support the safety portion of a request for EUA submission. FDA informed the Company that additional safety data that would be collected during the use of sabizabulin under the EUA, if granted, will be sufficient to support an NDA submission, and furthermore, that no additional safety clinical studies are required.

The Company plans to submit a request for an EUA application in calendar 2Q 2022.

The Company has scaled up manufacturing processes and will be able to produce commercial drug supply to address anticipated drug needs following potential FDA authorization and subsequent authorizations in the U.S. as well as other countries and regions.

The Company has initiated discussions with government agencies to discuss government purchases of sabizabulin in the U.S. and other countries around the world.

Breast Cancer Program

Enobosarm, a Novel Oral Selective Androgen Receptor Targeting Agonist, for the 3rd Line Treatment of AR+ ER+ HER2- Metastatic Breast Cancer with AR ≥ 40% Expression – Phase 3 ARTEST Clinical Study- Enrolling.

Enobosarm is an oral, new chemical entity, selective androgen receptor targeting agonist that activates the androgen receptor (AR), a tumor suppressor, in AR+ER+HER2- metastatic breast cancer without causing unwanted masculinizing side effects. Enobosarm has extensive nonclinical and clinical experience having been evaluated in 25 separate clinical studies in approximately 1,450 subjects dosed, including three Phase 2 clinical studies in advanced metastatic breast cancer involving more than 250 patients. In the two Phase 2 clinical studies conducted in women with AR+ER+HER2- metastatic breast cancer, enobosarm demonstrated significant antitumor efficacy in heavily pretreated cohorts that previously failed estrogen receptor blocking agents, chemotherapy, and/or CDK 4/6 inhibitors and enobosarm was well tolerated with a favorable safety profile.

We are enrolling the Phase 3 multicenter, international, open label, and randomized (1:1) ARTEST registration clinical trial design to evaluate enobosarm monotherapy versus physician’s choice of either exemestane everolimus or a selective estrogen receptor modulator (SERM) as the active comparator for the treatment of AR+ ER+ HER2- metastatic breast cancer in approximately 210 patients with AR expression ≥40% in their breast cancer tissue who had previously received a nonsteroidal aromatase inhibitor, fulvestrant, and a CDK4/6 inhibitor. In January 2022, the FDA granted Fast Track designation to the ARTEST Phase 3 registration program, a distinction that underscores the urgent need for novel, targeted therapies for this important unmet medical need.

Enobosarm and Abemaciclib, CDK 4/6 Inhibitor, Combination Therapy for the 2nd Line Treatment of AR+ER+HER2- Metastatic Breast Cancer with AR ≥ 40% Expression – Phase 3 ENABLAR-2 Clinical Study-Enrolling.

We are enrolling the Phase 3 multicenter, open label, randomized (1:1), active control clinical study, named ENABLAR-2 to evaluate the treatment of the enobosarm and abemaciclib combination versus an alternative estrogen blocking agent (fulvestrant or an aromatase inhibitor) in subjects with AR+ ER+ HER2- metastatic breast cancer who have failed first line palbociclib (a CDK 4/6 inhibitor) plus an estrogen blocking agent (non-steroidal aromatase inhibitor or fulvestrant) and who have an AR ≥ 40% expression in their breast cancer tissue in approximately 186 subjects. We have a clinical trial collaboration and supply agreement with Lilly for our Phase 3 ENABLAR-2 trial.

Sabizabulin, Novel Oral Cytoskeleton Disruptor Agent, for the 3rd Line Treatment of AR+ER+HER2- Metastatic Breast Cancer with AR< 40% Expression – Phase 2b Clinical Study.

We intend to conduct a Phase 2b clinical study which will be an open label, multicenter, and randomized (1:1) study evaluating sabizabulin 32mg monotherapy versus active comparator (exemestane ± everolimus or a SERM, physician’s choice) for the treatment of AR+ ER+ HER2- metastatic breast cancer in approximately 200 patients with AR <40% expression in their breast cancer tissue who have previously received a nonsteroidal aromatase inhibitor, fulvestrant, and a CDK4/6 inhibitor.

Prostate Cancer Program

Sabizabulin for the Treatment of Metastatic Castration and Androgen Receptor Targeting Agent Resistant Prostate Cancer – Phase 3 VERACITY Clinical Study – Enrolling.

The Company is enrolling the open label, randomized (2:1), multicenter Phase 3 VERACITY clinical study evaluating sabizabulin 32mg versus an alternative androgen receptor targeting agent for the treatment of chemotherapy naïve men with metastatic castration resistant prostate cancer who have tumor progression after previously receiving at least one androgen receptor targeting agent. The primary endpoint is radiographic progression free survival in approximately 245 patients from 45 clinical centers.

VERU-100, a Novel Proprietary Long-Acting Gonadotropin-Releasing Hormone (GnRH) Antagonist Peptide 3-Month Subcutaneous Depot Formulation, for Androgen Deprivation Therapy of Advanced Prostate Cancer – Phase 2 Clinical Study – Enrolling.

VERU-100 is designed to address the current limitations of commercially available androgen deprivation therapy. Androgen deprivation therapy is currently the mainstay of advanced prostate cancer treatment and is used as a foundation of treatment throughout the course of the disease even as other endocrine, chemotherapy, or radiation treatments are added or stopped. Specifically, VERU-100 is a chronic, long-acting GnRH antagonist peptide administered as a small volume, three-month depot subcutaneous injection without a loading dose. VERU-100 immediately suppresses testosterone with no testosterone surge upon initial or repeated administration, a problem that occurs with currently approved luteinizing hormone-releasing hormone agonists used for androgen deprivation therapy. There are no GnRH antagonist depot injectable formulations commercially approved beyond a one-month injection. In June 2021, the Company initiated the Phase 2 dose finding clinical study of VERU-100 androgen deprivation therapy for hormone sensitive advanced prostate cancer. The Phase 2 VERU-100 clinical study is expected to enroll approximately 45 patients. A Phase 3 registration clinical study has been agreed upon with FDA and will enroll approximately 100 men.

Urev – Sexual Health Division

ENTADFI (tadalafil and finasteride) capsule, a new Treatment for Benign Prostatic Hyperplasia (BPH) – Received FDA Approval.

We plan to market ENTADFI to healthcare providers and patients via digital tactics and distribution that will be conducted through the traditional pharmaceutical distribution channels, and potentially, a third-party telemedicine portal. We will augment our marketing and sales efforts by seeking partners in the U.S. and ex-U.S.

FC2 Female Condom/Internal Condom

The Company markets and sells the FC2, an FDA-approved product for dual protection against unplanned pregnancy and the transmission of sexually transmitted infections.

Event Details
Interested parties may access the call by dialing 1-800-341-1602 from the U.S. or 1-412-902-6706 from outside the U.S. and asking to be joined into the Veru Inc. call. The call will also be available through a live, listen-only audio broadcast via the Internet at www.verupharma.com. Listeners are encouraged to visit the website at least 10 minutes prior to the start of the scheduled presentation to register, download and install any necessary software. A playback of the call will be archived and accessible on the same website for at least three months. A telephonic replay of the conference call will be available, beginning the same day at approximately 12 p.m. (noon) ET by dialing 1-877-344-7529 for U.S. callers, or 1-412-317-0088 from outside the U.S., passcode 8215063, for one week.

On May 12, 2022 Imago BioSciences, Inc. ("Imago") (Nasdaq: IMGO), a clinical stage biopharmaceutical company discovering and developing new medicines for the treatment of myeloproliferative neoplasms (MPNs) and other bone marrow diseases, reported that updated Phase 2 data from its two clinical programs for bomedemstat (IMG-7289) have been accepted for poster presentation at the 27th Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) for 2022, to be held on June 9-12, 2022 in Vienna, Austria and virtually (Press release, Imago BioSciences, MAY 12, 2022, View Source [SID1234614325]).

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Details on Imago’s EHA (Free EHA Whitepaper) 2022 Presentations:

Poster Presentation Title: A Phase 2 Study of IMG-7289 (Bomedemstat) in Patients with Advanced Myelofibrosis

Abstract Number: EHA (Free EHA Whitepaper)-2824

Final Abstract Code: P1051

Presentation Date & Time: Friday, June 10 2022 – 16:30 – 17:45 CEST

Presenting Author: Harinder Gill

Poster Presentation Title: A Phase 2 Study of the LSD1 Inhibitor IMG-7289 (Bomedemstat) for the Treatment of Essential Thrombocythemia (ET)

Abstract Number: EHA (Free EHA Whitepaper)-2792

Final Abstract Code: P1033

Presentation Date & Time: Friday, June 10 2022 – 16:30 – 17:45 CEST

Presenting Author: Francesca Palandri

The abstracts are available on the EHA (Free EHA Whitepaper) 2022 Annual Congress meeting website at the EHA (Free EHA Whitepaper) Web Library.

On May 12, 2022 CTI BioPharma Corp. (Nasdaq: CTIC) reported its financial results for the first quarter ended March 31, 2022 (Press release, CTI BioPharma, MAY 12, 2022, View Source [SID1234614342]).

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"With the accelerated FDA approval and U.S. commercial launch of VONJO, the first quarter was transformational for CTI and the myelofibrosis community. We are thrilled to now be delivering VONJO for patients with cytopenic myelofibrosis who have platelet counts below 50 x 109/L. Our U.S. commercial team has been in the field since early March and has delivered net product revenue of $2.3 million in less than a month, exceeding our internal expectations and establishing a great foundation for future performance," said Adam Craig, President and Chief Executive Officer of CTI BioPharma. "We are also pleased that NCCN quickly recommended VONJO for the treatment of myelofibrosis, making VONJO the only approved JAK inhibitor recommended by NCCN for these patients regardless of platelet counts."

Recent Accomplishments and Updates

FDA accelerated approval for VONJO for the treatment of adults with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with a platelet count below 50 × 109/L.
U.S. commercial launch in early March by fully funded sales and marketing team.
$60 million payment from DRI Healthcare Trust for the acquisition of a tiered royalty for VONJO.
VONJO included as recommended treatment in the latest National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for Myeloproliferative Neoplasms, as a first-line treatment for high-risk patients with myelofibrosis with platelet counts <50 x 109/L who are not candidates for transplant, and as a second-line treatment for lower-risk and higher-risk patients with myelofibrosis with platelet counts ≥50 x 109/L who are not candidates for transplant.
Accepted abstract at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held June 3–7, 2022, in Chicago and virtually:
Abstract Title: Risk-adjusted safety analysis of pacritinib (PAC) in patients (pts) with myelofibrosis (MF)
Abstract Number: 7058
Session Name: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant
Session Date: Saturday, June 4, 2022
Presentation Time: 8:00 – 11:00 a.m. CDT (9:00 a.m. – 12:00 p.m. ET)
Presenter: Dr. Naveen Pemmaraju
Accepted abstracts at the European Hematology Association (EHA) (Free EHA Whitepaper) 2022 Congress being held June 9–12, 2022, in Vienna, Austria:
Abstract Title: Risk-adjusted safety analysis of pacritinib in patients with myelofibrosis
Abstract Number: P1068
Session Name: Poster session
Session Date: Friday, June 10, 2022
Presentation Time: 16:30 – 17:45 CEST (10:30 – 11:45 a.m. ET)
Presenter: Dr Naveen Pemmaraju
Abstract Title: Retrospective comparison of patient outcomes on pacritinib versus ruxolitinib in patients with myelofibrosis and thrombocytopenia
Abstract Number: P1069
Session Name: Poster session
Session Date: Friday, June 10, 2022
Presentation Time: 16:30 – 17:45 CEST (10:30 – 11:45 a.m. ET)
Presenter: Prof. Claire Harrison
First Quarter Financial Results

Net product sales of $2.3 million for the first quarter ended March 31, 2022 were attributable to VONJO product sales in the United States. There were no product sales for the comparable period in 2021. Our realization of future product sales will be dependent, in part, upon our commercialization efforts and the market acceptance of VONJO among physicians, patients, healthcare payers and the medical community.

Operating loss was $35.1 million and $17.1 million for the three months ended March 31, 2022 and 2021, respectively. The increase in operating loss between periods resulted primarily from increases in selling, general and administrative activities related to the commercial-launch of VONJO and the growth in our commercial infrastructure, as well as a $10.3 million milestone expense related to FDA approval of VONJO, which was included in other operating expenses for the three months ended March 31, 2022.

Net loss for the three months ended March 31, 2022 was $37.2 million, or $0.37 for basic and diluted loss per share, compared to net loss of $17.3 million, or $0.23 for basic and diluted loss per share, for the same period in 2021.

As of March 31, 2022, our cash and cash equivalents totaled $96.9 million. We expect our present financial resources, including expected cash receipts from receivables arising from historical net product sales of VONJO (but excluding any proceeds of future net product sales of VONJO), will enable us to fund our operations into the first quarter of 2023. In accordance with applicable accounting standards, our evaluation of our expected cash runway considers only relevant conditions and events that are known or reasonably knowable at the date that the financial statements are issued. As a result, our cash runway evaluation did not include VONJO sales that we may recognize in the future. We expect to include future net product sales of VONJO in our cash runway projections once we have an established history of such sales.

Conference Call and Webcast

CTI will host a conference call and webcast to review its first quarter 2022 financial results and provide an update on business activities today, May 12 at 4:30 p.m. ET. To access the live call by phone please dial (877) 735-2860 (domestic) or (602) 563-8791 (international); the conference ID is 7291915. A live audio webcast of the event may also be accessed through the "Investors" section of CTI’s website at www.ctibiopharma.com. A replay of the webcast will be available for 30 days following the event.

About VONJO (pacritinib)
Pacritinib is an oral kinase inhibitor with activity against wild type Janus Associated Kinase 2 (JAK2), mutant JAK2V617F form and FMS-like tyrosine kinase 3 (FLT3), which contribute to signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function. Myelofibrosis is often associated with dysregulated JAK2 signaling. Pacritinib has higher inhibitory activity for JAK2 over other family members, JAK3 and TYK2. At clinically relevant concentrations, pacritinib does not inhibit JAK1. Pacritinib exhibits inhibitory activity against additional cellular kinases (such as CSF1R and IRAK1), the clinical relevance of which is unknown.

VONJO is indicated for the treatment of adults with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with a platelet count below 50 × 109/L. This indication is approved under accelerated approval based on spleen volume reduction. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Important VONJO Safety Information
Hemorrhage:
Serious (11%) and fatal (2%) hemorrhages have occurred in VONJO-treated patients with platelet counts <100 × 109/L. Serious (13%) and fatal (2%) hemorrhages have occurred in VONJO-treated patients with platelet counts <50 × 109/L. Grade ≥3 bleeding events (defined as requiring transfusion or invasive intervention) occurred in 15% of patients treated with VONJO compared to 7% of patients treated on the control arm. Due to hemorrhage, VONJO dose-reductions, dose interruptions, or permanent discontinuations occurred in 3%, 3%, and 5% of patients, respectively.

Avoid use of VONJO in patients with active bleeding and hold VONJO 7 days prior to any planned surgical or invasive procedures. Assess platelet counts periodically, as clinically indicated. Manage hemorrhage using treatment interruption and medical intervention.

Diarrhea:
VONJO causes diarrhea in approximately 48% of patients compared to 15% of patients treated on the control arm. The median time to resolution in VONJO-treated patients was 2 weeks. The incidence of reported diarrhea decreased over time with 41% of patients reporting diarrhea in the first 8 weeks of treatment, 15% in Weeks 8 through 16, and 8% in Weeks 16 through 24. Diarrhea resulted in treatment interruption in 3% of VONJO-treated patients. None of the VONJO-treated patients reported diarrhea that resulted in treatment discontinuation. Serious diarrhea adverse reactions occurred in 2% of patients treated with VONJO compared to no such adverse reactions in patients in the control arm.

Control pre-existing diarrhea before starting VONJO treatment. Manage diarrhea with antidiarrheal medications, fluid replacement, and dose-modification. Treat diarrhea with anti–diarrheal medications promptly at the first onset of symptoms. Interrupt or reduce VONJO dose in patients with significant diarrhea despite optimal supportive care.

Thrombocytopenia:
VONJO can cause worsening thrombocytopenia. VONJO dosing was reduced due to worsening thrombocytopenia in 2% of patients with pre–existing moderate to severe thrombocytopenia (platelet count <100 × 109/L). VONJO dosing was reduced due to worsening thrombocytopenia in 2% of patients with pre–existing severe thrombocytopenia (platelet count <50 × 109/L).

Monitor platelet count prior to VONJO treatment and as clinically indicated during treatment. Interrupt VONJO in patients with clinically significant worsening of thrombocytopenia that lasts for more than 7 days. Restart VONJO at 50% of the last given dose once the toxicity has resolved. If toxicity recurs hold VONJO. Restart VONJO at 50% of the last given dose once the toxicity has resolved.

Prolonged QT interval:
VONJO can cause prolongation of the QTc interval. QTc prolongation of >500 msec was higher in VONJO-treated patients than in patients in the control arm (1.4% vs 1%). QTc increase from baseline by 60 msec or higher was greater in VONJO-treated patients than in control arm patients (1.9% vs 1%). Adverse reactions of QTc prolongation were reported for 3.8% of VONJO-treated patients and 2% of control arm patients. No cases of torsades de pointes were reported.

Avoid use of VONJO in patients with a baseline QTc of >480 msec. Avoid use of drugs with significant potential for QTc prolongation in combination with VONJO. Correct hypokalemia prior to and during VONJO treatment. Manage QTc prolongation using VONJO interruption and electrolyte management.

Major Adverse Cardiac Events (MACE):
Another Janus associated kinase (JAK)-inhibitor has increased the risk of MACE, including cardiovascular death, myocardial infarction, and stroke (compared to those treated with TNF blockers) in patients with rheumatoid arthritis, a condition for which VONJO is not indicated.

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with VONJO particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur.

Thrombosis:
Another JAK-inhibitor has increased the risk of thrombosis, including deep venous thrombosis, pulmonary embolism, and arterial thrombosis (compared to those treated with TNF blockers) in patients with rheumatoid arthritis, a condition for which VONJO is not indicated.

Patients with symptoms of thrombosis should be promptly evaluated and treated appropriately.

Secondary Malignancies:
Another JAK-inhibitor has increased the risk of lymphoma and other malignancies excluding non-melanoma skin cancer (NMSC) (compared to those treated with TNF blockers) in patients with rheumatoid arthritis, a condition for which VONJO is not indicated. Patients who are current or past smokers are at additional increased risk.

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with

VONJO, particularly in patients with a known malignancy (other than a successfully treated NMSC), patients who develop a malignancy, and patients who are current or past smokers.

Risk of Infection:
Another JAK-inhibitor has increased the risk of serious infections (compared to best available therapy) in patients with myeloproliferative neoplasms. Serious bacterial, mycobacterial, fungal and viral infections may occur in patients treated with VONJO. Delay starting therapy with VONJO until active serious infections have resolved. Observe patients receiving VONJO for signs and symptoms of infection and manage promptly. Use active surveillance and prophylactic antibiotics according to clinical guidelines.

Interactions with CYP3A4 Inhibitors or Inducers:
Co-administration of VONJO with strong CYP3A4 inhibitors or inducers is contraindicated. Avoid concomitant use of VONJO with moderate CYP3A4 inhibitors or inducers.

Drug interruptions due to an adverse reaction occurred in 27% patients who received VONJO 200 mg twice daily compared to 10% of patients treated with BAT. Dosage reductions due to an adverse reaction occurred in 12% of patients who received VONJO 200 mg twice daily compared to 7% of patients treated with BAT. Permanent discontinuation due to an adverse reaction occurred in 15% of patients receiving VONJO 200 mg twice daily compared to 12% of patients treated with BAT.

Please visit View Source for full Prescribing Information and the Medication Guide.

About Myelofibrosis

Myelofibrosis is bone marrow cancer that results in formation of fibrous scar tissue and can lead to thrombocytopenia and anemia, weakness, fatigue and an enlarged spleen and liver. Within the United States, there are approximately 21,000 patients with myelofibrosis, 7,000 of which have severe thrombocytopenia (defined as blood platelet counts of less than 50 x109/L). Severe thrombocytopenia is associated with poor survival and high symptom burden and can occur as a result of disease progression or from drug toxicity with other JAK2 inhibitors, such as JAKAFI and INREBIC.

On May 12, 2022 Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a precision oncology medicine company pioneering the discovery and development of MasterKey therapies, reported the publication of data identifying new oncogenic HER2 allosteric mutations that support the Mutation-Allostery-Pharmacology (MAP) discovery engine’s capabilities and further suggest the need for novel inhibitors to treat HER2-mutant cancers (Press release, Black Diamond Therapeutics, MAY 12, 2022, View Source [SID1234614359]). The paper, titled "Computational and Functional Analyses of HER2 Mutations Revealing Allosteric Activation Mechanisms and Altered Pharmacologic Effects" by Ishiyama et al. was published online by the American Association for Cancer Research (AACR) (Free AACR Whitepaper)’s Cancer Research Journal on May 3, 2022.

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"At the core of our precision medicine approach to cancer treatment is the ability to identify new, full spectrum oncogenic mutations. This study provides strong rationale for the power of our MAP discovery engine as we identified new oncogenic HER2 allosteric mutations that further suggest the need for novel treatment options. These findings support our overall approach to cancer treatment by demonstrating the value and importance of oncogenicity prediction, biological validation, protein conformation-based drug design and MasterKey inhibitor development against mutation families," said Elizabeth Buck, Chief Scientific Officer of Black Diamond Therapeutics. "In this study, Black Diamond’s proprietary MAP-scoring and functional validation analyses were able to provide new insights into the oncogenic activity and therapeutic targeting of HER2 mutations in cancer in addition to identifying 22 new oncogenic HER2 mutations. As the number of unique mutations across cancers is expected to rise over time, there remains a need for an effective means of identification of oncogenic mutations. We believe that our MAP technology has the potential to fill this gap and provide critical insights for the use of precision medicine to treat cancers driven by rare oncogenic mutations."

The peer-reviewed paper describes computational and functional analyses of HER2 mutations showing that Black Diamond’s MAP discovery engine has the ability to identify and experimentally validate 22 new oncogenic HER2 driver mutations. By applying its computational approach to 820 single-nucleotide variants, a list of 222 known mutations and potential driver mutations was produced. Of these 222 mutations, 37 HER2 mutations were experimentally determined to be driver mutations, comprised of 15 previously characterized and 22 newly identified oncogenic mutations. Black Diamond researchers found that these oncogenic mutations mostly affected allosteric sites in the extracellular domain (ECD), transmembrane domain (TMD), and kinase domain (KD) of HER2. In addition, Black Diamond was able to describe the unique pharmacological characteristics of these new HER2 driver mutations that render them susceptible to unique drug discovery screening strategy.