On November 4, 2021 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium" or the "Company"), a leader in the development of targeted radiotherapies for patients with unmet needs, reported that the Phase 1 trial studying Actimab-A with the salvage chemotherapy CLAG-M in patients with relapsed or refractory acute myeloid leukemia (r/r AML) who are fit for intensive therapy has completed the planned dose escalation and patient enrollment. Patients in the fourth and final dose escalation cohort received 1.0 μCi/kg of Actimab-A with the standard CLAG-M dose regimen (Press release, Actinium Pharmaceuticals, NOV 4, 2021, View Source [SID1234594506]). This novel combination trial is being conducted at the Medical College of Wisconsin. Updated Phase 1 data is expected will be presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December and Actinium expects to provide an update on the future clinical development of this combination by year end.

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Actimab-A CLAG-M combination data was presented at ASH (Free ASH Whitepaper) 2020 from the first three dose cohorts, which highlighted:

100% remission rate (CR/CRi) in patients receiving 0.75 μCi/kg of Actimab-A with CLAG-M
83% remission rate in patients who received 3 or fewer lines of prior treatment
70% of patients achieving a remission were MRD negative
67% of patients in the study achieved a remission including patients receiving 0.25 and 0.50 μCi/kg of Actimab-A, which has shown to be subtherapeutic as a single agent in prior studies
All patients had intermediate (N=5, 33%) or adverse (N=10, 67%) cytogenetics
Patients had a median of 2 prior therapies (range:1- 5) including prior Venetoclax/HMA (N=7,47%) or bone marrow transplant (N=8, 53%)
These results compare favorably to outcomes with CLAG-M as a single agent, which was shown in a separate study to have a 55% overall response rate and a 39% MRD negativity rate.

Dr. Avinash Desai, Actinium’s Chief Medical Officer, said, "This novel combination has produced promising data with high rates of remission and MRD negativity with an acceptable safety profile thus far. Despite multiple new drug approvals for patients with AML, including several targeted agents, outcomes for patients with relapsed or refractory AML remain poor, especially those with adverse molecular or cytogenetic features. Actimab-A enables the treatment of AML with radiation at a cellular level, which is a novel mechanism not achievable with traditional external beam radiation given the diffuse nature of blood cancers like AML. Given the sensitivity of AML and other blood cancers to radiation, we are optimistic in its potential to improve patient outcomes. We hypothesized that the combination of Actimab-A with CLAG-M would be tolerable given the non-overlapping mechanisms of action and lead to higher and deeper remissions. We have been very pleased with the data from the trial to date and look forward to advancing this novel combination once we have reviewed the data from all dose cohorts, including the data to be presented at ASH (Free ASH Whitepaper) in December."

On November 4, 2021 Legend Biotech Corporation (NASDAQ: LEGN) (Legend Biotech), a global, clinical-stage biotechnology company developing and manufacturing novel therapies, reported that 12 company-sponsored studies were accepted for presentation at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (Press release, Legend Biotech, NOV 4, 2021, View Source [SID1234594523]). These include two oral presentations and 10 poster presentations .

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Presentation highlights include updates from the CARTITUDE clinical development program for the investigational B-cell maturation antigen (BCMA) directed chimeric antigen receptor T cell (CAR-T) therapy, ciltacabtagene autoleucel (cilta-cel), for the treatment of patients with relapsed or refractory multiple myeloma (RRMM). Presentations will detail longer-term follow-up data and new sub-group analysis results from the Phase 1b/2 CARTITUDE-1 study as well as adjusted indirect comparison of CARTITUDE-1 patient outcomes relative to standard-of-care therapies in real-world clinical practice from the LocoMMotion study. First data release from Cohort B and longer-term follow-up data from Cohort A of the CARTITUDE-2 study in earlier lines of treatments will be presented.

Additionally, Legend will share the first preclinical in vivo data on its novel tri-specific single-domain antibody (VHH) CAR-T (LCAR-AIO). LCAR-AIO targets three antigens—CD19, CD20 and CD22—with the potential for development as a treatment for patients with relapsed B cell lymphoma and prior CD19 CAR-T therapies.

"The new and updated data from the CARTITUDE-1 and CARTITUDE-2 studies show that cilta-cel continues to provide early, deep and durable responses, even in high-risk patients," said Ying Huang, PhD, CEO and CFO of Legend Biotech. "What’s also encouraging is the new preclinical data from our novel tri-specific VHH CAR-T, which was designed and developed by Legend. This trispecific CAR-T exemplifies our team’s ability to discover novel mechanisms of action by screening and optimizing antibodies in house."

A select list of abstracts from the meeting can be found below.

ASH Presentations (December 11-14, 2021)

Abstract No.

Title

INFO

Abstract #549
Oral

Updated Results From CARTITUDE-1: Phase 1b/2 Study of Ciltacabtagene Autoleucel, a B-cell Maturation Antigen–Directed Chimeric Antigen Receptor T Cell Therapy, in Patients with Relapsed/Refractory Multiple Myeloma

Session Title: 704. Cellular Immunotherapies: Cellular Therapies for Myeloma

Date/Time: Sunday, December 12, 2021 4:30 PM – 6:00 PM EST

Presentation time: 5:00 PM EST

Room: Georgia World Congress Center, Hall C2-C3

Abstract #550

Oral

Ciltacabtagene Autoleucel for Triple-Class Exposed Multiple Myeloma: Adjusted Comparisons of CARTITUDE-1 Patient Outcomes Versus Therapies from Real-World Clinical Practice from the LocoMMotion Prospective Study

Session Title: 704. Cellular Immunotherapies: Cellular Therapies for Myeloma

Date/Time: Sunday, December 12, 2021 4:30 PM – 6:00 PM EST

Presentation time: 5:15 PM EST

Location: Georgia World Congress Center, Hall C2-C3

Abstract#3938

Poster

Efficacy and Safety of Ciltacabtagene Autoleucel in Patients with Relapsed/Refractory Multiple Myeloma: CARTITUDE-1 Subgroup Analysis

Session Title: 731. Autologous Transplantation: Clinical and Epidemiological: Poster III

Date/Time: Monday, December 13, 2021 6:00 PM – 8:00 PM EST

Location: Georgia World Congress Center, Hall B5

Abstract #2812

Poster

Anakinra Targeting Cytokine Release Syndrome Associated with Chimeric Antigen Receptor T-cell Therapies

Session Title: 704. Cellular Immunotherapies: Clinical: Poster II

Date/Time: Sunday, December 12, 2021 6:00 PM – 8:00 PM EST

Location: Georgia World Congress Center, Hall B5

Abstract #3866

Poster

Efficacy and Safety of Ciltacabtagene Autoleucel (Cilta-cel), a B-cell Maturation Antigen–Directed Chimeric Antigen Receptor T-cell Therapy, in Lenalidomide-Refractory Patients with Progressive Multiple Myeloma After 1–3 Prior Lines of Therapy: Updated

Results From CARTITUDE-2

Session Title: 704. Cellular Immunotherapies: Clinical: Poster III

Date/Time: Monday, December 13, 2021 6:00 PM – 8:00 PM EST

Location: Georgia World Congress Center, Hall B5

Abstract #2910

Poster

CARTITUDE-2: Efficacy and Safety of Ciltacabtagene Autoleucel (Cilta-cel), a B-cell Maturation Antigen (BCMA)-Directed Chimeric Antigen Receptor T Cell (CAR T) Therapy, in Patients with Multiple Myeloma and Early Relapse After Initial Therapy

Session Title: 731. Autologous Transplantation: Clinical and Epidemiological: Poster II

Date/Time: Sunday, December 12, 2021 6:00 PM – 8:00 PM EST

Location: Georgia World Congress Center, Hall B5

Abstract #1835

Poster

Bortezomib, Lenalidomide, and Dexamethasone (VRd) Followed by Ciltacabtagene Autoleucel vs VRd Followed by Lenalidomide and Dexamethasone (Rd) Maintenance in Patients with Newly Diagnosed Multiple Myeloma Not Intended for Transplant: A Randomized, Phase 3 Study (CARTITUDE-5)

Session Title: 731. Autologous Transplantation: Clinical and Epidemiological: Poster I

Date/Time: Saturday, December 11, 2021 5:30 PM – 7:30 PM EST

Location: Georgia World Congress Center, Hall B5

Abstract #3057

Poster

LocoMMotion: A Prospective, Non-interventional, Multinational Study of Real-life Current Standards of Care in Patients with Relapsed/Refractory Multiple Myeloma Who Received ≥3 Prior Lines of Therapy

Session Title: 905. Outcomes Research—Lymphoid Malignancies: Poster II

Date/Time: Sunday, December 12, 2021 6:00 PM – 8:00 PM EST

Location: Georgia World Congress Center, Hall B5

Abstract #1676

Poster

Meta-analysis of Ciltacabtagene Autoleucel versus Physician’s Choice in the Treatment of Patients with Relapsed or Refractory Multiple Myeloma

Session Title: 653. Myeloma and Plasma Cell Dyscrasias: Clinical-Prospective Therapeutic Trials: Poster I

Date/Time: Saturday, December 11, 2021 5:30 PM – 7:30 PM

Location: Georgia World Congress Center, Hall B5

Abstract #4075

Poster

Real-World Outcomes for Standard-Of-Care Treatments in Patients with Relapsed/Refractory Multiple Myeloma

Session Title: 905. Outcomes Research—Lymphoid Malignancies: Poster III

Date/Time: Monday, December 13, 2021 6:00 PM – 8:00 PM EST

Location: Georgia World Congress Center, Hall B5

Abstract #1932

Poster

Considerations for optimal administration of Chimeric Antigen Receptor (CAR) T-Cell therapy programs: a multi-stakeholder qualitative analysis

Session Title: 902. Health Services Research—Lymphoid Malignancies: Poster I

Date/Time: Saturday, December 11, 2021 5:30 PM – 7:30 PM

Location: Georgia World Congress Center, Hall B5

Abstract #1700

Poster

Tri-specific CD19xCD20xCD22 VHH CAR-T cells (LCAR-AIO) eradicate antigen-heterogeneous B cell tumors, enhance expansion, and prolong persistence in preclinical in vivo models

Session Title: 703. Cellular Immunotherapies: Basic and Translational: Poster I

Date: Saturday, December 11, 2021 5:30-7:30 PM

Location: Georgia World Congress Center, Hall B5

About CARTITUDE-1

CARTITUDE-1 (NCT03548207) is a Phase 1b/2, open-label, multicenter study evaluating the safety and efficacy of cilta-cel in adults with relapsed or refractory with multiple myeloma, who previously received a proteasome inhibitor (PI), an immunomodulatory agent (IMiD) and an anti-CD38 antibody, and who had disease progression on or after the last regimen.1 The primary objective of the Phase 1b portion of the study was to characterize the safety and confirm the recommended Phase 2 dose of cilta-cel, informed by the first-in-human study with LCAR-B38M CAR-T cells (LEGEND-2). The Phase 2 portion further evaluated the efficacy of cilta-cel with overall response rate as the primary endpoint. Of the 97 patients enrolled in the trial, 99 percent were refractory to the last line of treatment and 88 percent were triple-class refractory, meaning their cancer did not respond, or no longer responds, to an IMiD, a PI and an anti-CD38 antibody.

About CARTITUDE-2

CARTITUDE-2 (NCT04133636) is an ongoing Phase 2 multicohort study evaluating the safety and efficacy of cilta-cel in various clinical settings. Cohort A included patients who had progressive multiple myeloma after 1–3 prior lines of therapy, including PI and IMiD, were lenalidomide refractory, and had no prior exposure to BCMA-targeting agents. Cohort B included patients with early relapse after initial therapy that included a PI and IMiD. The primary objective was percentage of patients with negative minimal residual disease (MRD).2

About CARTITUDE-5

CARTITUDE-5 (NCT04923893) is a Phase 3 open-label study of bortezomib, lenalidomide, and dexamethasone (VRd) followed by cilta-cel vs. VRd followed by Rd maintenance, in patients with newly diagnosed MM for whom autologous stem cell transplant (ASCT) is not planned as initial therapy.

About LocoMMotion

LocoMMotion (NCT04035226) is a prospective non-interventional study evaluating the safety and efficacy of real-life standard-of-care treatments under routine clinical practice over a 24-month period in patients with RRMM. This study aims to understand the effectiveness of current standards of care in heavily pretreated patients with RRMM (reflecting real-world practice in the patient population progressing after PIs, IMiDs and anti-CD38 antibodies).

About Multiple Myeloma
Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excessive proliferation of plasma cells.3 Although treatment may result in remission, unfortunately, patients will most likely relapse.4 Relapsed myeloma is when the disease has returned after a period of initial, partial or complete remission and does not meet the definition of being refractory.5 Refractory multiple myeloma is when a patient’s disease is non-responsive or progresses within 60 days of their last therapy.6,7 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems or infections. 8 Patients who relapse after treatment with standard therapies, including protease inhibitors and immunomodulatory agents, have poor prognoses and few treatment options available.9

About Cilta-cel
Cilta-cel is an investigational chimeric antigen receptor T cell (CAR-T) therapy, formerly identified as JNJ-4528 in the U.S. and Europe and LCAR-B38M CAR-T cells in China, that is being studied in a comprehensive clinical development program for the treatment of patients with relapsed or refractory multiple myeloma and in earlier lines of treatment. The design consists of a structurally differentiated CAR-T with two BCMA-targeting single domain antibodies. In December 2017, Legend Biotech, Inc. entered into an exclusive worldwide license and collaboration agreement with Janssen Biotech, Inc. (Janssen) to develop and commercialize cilta-cel. In addition to a Breakthrough Therapy Designation (BTD) granted in the U.S. in December 2019, cilta-cel received a Priority Medicines (PRiME) designation from the European Commission in April 2019, and a BTD in China in August 2020. In addition, Orphan Drug Designation was granted for cilta-cel by the U.S. FDA in February 2019, and by the European Commission in February 2020. A Biologics License Application seeking approval of cilta-cel was submitted to the U.S. FDA and a Marketing Authorization Application was submitted to the European Medicines Agency.

On November 4, 2021 Puma Biotechnology, Inc. (Nasdaq: PBYI), a biopharmaceutical company, reported financial results for the third quarter ended September 30, 2021 (Press release, Puma Biotechnology, NOV 4, 2021, View Source [SID1234594541]). Unless otherwise stated, all comparisons are for the third quarter of 2021 compared to the third quarter of 2020.

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"Our operating results continued to be negatively impacted by the effects of COVID-19 and its limitations to our access to healthcare providers during the third quarter"

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Product revenue, net consists entirely of sales revenue from NERLYNX, Puma’s first commercial product. Product revenue, net for the third quarter of 2021 was $43.4 million, compared to product revenue, net of $49.3 million for the third quarter of 2020. Product revenue, net for the first nine months of 2021 was $138.1 million, compared to product revenue, net of $146.7 million for the first nine months of 2020.

Based on accounting principles generally accepted in the United States (GAAP), Puma reported a net loss of $44.7 million, or $1.09 per share, for the third quarter of 2021, compared to a net loss of $31.5 million, or $0.79 per share, for the third quarter of 2020. Net loss for the first nine months of 2021 was $33.4 million, or $0.82 per share, compared to a net loss of $45.0 million, or $1.14 per share, for the first nine months of 2020.

Non-GAAP adjusted net loss was $40.4 million, or $0.99 per share, for the third quarter of 2021, compared to non-GAAP adjusted net loss of $23.9 million, or $0.60 per share, for the third quarter of 2020. Non-GAAP adjusted net loss for the first nine months of 2021 was $5.0 million, or $0.12 per share, compared to non-GAAP adjusted net loss of $17.9 million, or $0.45 per share, for the first nine months of 2020. Non-GAAP adjusted net loss excludes stock-based compensation expense. For a reconciliation of GAAP net loss to non-GAAP adjusted net loss and GAAP net loss per share to non-GAAP adjusted net loss per share, please see the financial tables at the end of this news release.

Net cash provided by operating activities for the third quarter of 2021 was $10.5 million, compared to net cash provided by operating activities of $1.7 million for the third quarter of 2020. Net cash provided by operating activities for the first nine months of 2021 was $26.1 million, compared to net cash provided by operating activities of $6.4 million for the first nine months of 2020. At September 30, 2021, Puma had cash, cash equivalents and marketable securities of $87.5 million, compared to cash, cash equivalents and marketable securities of $93.4 million at December 31, 2020.

"Our operating results continued to be negatively impacted by the effects of COVID-19 and its limitations to our access to healthcare providers during the third quarter," said Alan H. Auerbach, Chairman, Chief Executive Officer and President of Puma. "Net revenue for the quarter was also negatively impacted by approximately $3.5 million due to inventory reduction at our specialty pharmacies and specialty distributors. We are encouraged with the uptake in the implementation of dose escalation of NERLYNX that was seen in the quarter, which we believe is due to the label expansion that occurred in July. We are also pleased with the continued commercial progress of NERLYNX globally, with the most recent regulatory approval received in the South Korean market by our sub-licensee Bixink Therapeutics. Our team remains committed to providing support to patients battling breast cancer, and we look forward to providing updated neratinib clinical trial data at the San Antonio Breast Cancer Symposium next month."

Mr. Auerbach added, "We anticipate the following key milestones over the next 12 months: (i) reporting top line data from the randomized cohort of the Phase II SUMMIT trial of neratinib in hormone receptor positive breast cancer that has a HER2 mutation (Q4 2021); (ii) reporting data from the Phase II INSIGhT trial of neratinib in patients with glioblastoma at the Society of NeuroOncology (SNO) Annual Meeting (Q4 2021); (iii) conducting a Type C meeting with the FDA to discuss potential for accelerated approval of neratinib in HER2-mutated hormone receptor positive breast cancer (Q4 2021); (iv) reporting data from the Phase II TBCRC-022 trial of the combination of Kadcyla plus neratinib in patients with HER2-positive breast cancer with brain metastases who have previously been treated with Kadcyla (H1 2022); (v) reporting Phase II data from the SUMMIT trial of neratinib in non-small cell lung cancer patients with EGFR exon 18 mutations (H1 2022); (vi) conducting a meeting with the FDA to discuss the potential for an accelerated approval pathway for neratinib in non-small cell lung cancer patients with EGFR exon 18 mutations who have previously been treated with an EGFR tyrosine kinase inhibitor (2022); (vii) reporting Phase II data from the SUMMIT trial of neratinib in cervical cancer patients with HER2 mutations (H1 2022); and (viii) receiving regulatory decisions for the extended adjuvant HER2-positive early stage breast cancer indication in additional countries (Q4 2021/H1 2022)."

Revenue

Total revenue consists of product revenue, net from sales of NERLYNX, license revenue and royalty revenue. For the third quarter of 2021, total revenue was $46.2 million, of which $43.4 million was product revenue, net and $2.8 million was royalty revenue. This compares to total revenue of $50.8 million for the third quarter of 2020, of which $49.3 million was product revenue, net and $1.5 million was royalty revenue. For the first nine months of 2021, total revenue was $197.8 million, of which $138.1 million was product revenue, net, $50.3 million was license revenue received from Puma’s sub-licensees, which included a $50 million upfront payment for providing development, manufacturing and commercial rights to NERLYNX in Greater China to Pierre Fabre, and $9.4 million was royalty revenue. This compares to total revenue of $172.6 million for the first nine months of 2020, of which $146.7 million was product revenue, net, $22.7 million was license revenue from Puma’s sub-licensees, and $3.2 million was royalty revenue.

Operating Costs and Expenses

Total operating costs and expenses were $55.2 million for the third quarter of 2021, compared to $62.9 million for the third quarter of 2020. Operating costs and expenses for the first nine months of 2021 were $203.3 million, compared to $191.8 million for the first nine months of 2020.

Cost of Sales

Cost of sales was $10.3 million for the third quarter of 2021, compared to $10.0 million for the third quarter of 2020. Cost of sales was $51.8 million for the first nine months of 2021, of which $20.0 million was a termination fee paid to a former sub-licensee for the return of commercial rights to NERLYNX in Greater China, compared to cost of sales of $28.4 million for the first nine months of 2020.

Selling, General and Administrative Expenses

Selling, general and administrative (SG&A) expenses were $26.1 million for the third quarter of 2021, compared to $29.6 million for the third quarter of 2020. SG&A expenses for the first nine months of 2021 were $93.8 million, compared to $89.9 million for the first nine months of 2020.

The $3.9 million increase in SG&A expenses for the first nine months of 2021 compared to the first nine months of 2020 resulted primarily from an increase in stock-based compensation of approximately $9.8 million, partially offset by decreases in payroll and related costs of approximately $1.5 million, professional fees and expenses of approximately $2.2 million, travel and meetings costs of approximately $0.6 million, and other expenses of approximately $1.3 million.

The $9.8 million increase in stock-based compensation expense for the first nine months of 2021 consisted of a $13.6 million incremental expense resulting from a modification to the term of Mr. Auerbach’s warrant and an increase of $3.4 million from new grants, partially offset by decreases of approximately $5.9 million for stock awards that have fully vested and $1.3 million from stock awards forfeited.

Research and Development Expenses

Research and development (R&D) expenses were $18.8 million for the third quarter of 2021, compared to $23.3 million for the third quarter of 2020. R&D expenses for the first nine months of 2021 were $57.7 million, compared to $73.5 million for the first nine months of 2020.

The $15.8 million decrease in R&D expenses for the first nine months of 2021 compared to the first nine months of 2020 resulted primarily from decreases in stock-based compensation expense of approximately $8.5 million, clinical trial expenses of approximately $2.6 million, internal R&D expenses of approximately $3.3 million, and consultant and contractors’ costs of approximately $1.3 million.

Total Other Expenses

Total other expenses were $35.7 million for the third quarter of 2021, compared to $19.4 million for the third quarter of 2020. Total other expenses were $27.7 million for the first nine months of 2021, compared to $25.8 million for the first nine months of 2020. The $1.9 million increase for the first nine months of 2021 compared to the first nine months of 2020 resulted primarily from an increase in debt extinguishment loss of approximately $8.1 million, partially offset by a decrease in legal verdict expense of approximately $6.2 million and other immaterial fluctuations.

Conference Call

Puma Biotechnology will host a conference call to report its third quarter 2021 financial results and provide an update on the Company’s business and outlook at 1:30 p.m. PDT/4:30 p.m. EDT on Thursday, November 4, 2021. The call may be accessed by dialing 1-888-437-3179 (domestic) or 1-862-298-0702 (international). Please dial in at least 10 minutes in advance and inform the operator that you would like to join the "Puma Biotechnology Conference Call." A live webcast of the conference call and presentation slides may be accessed on the Investors section of the Puma Biotechnology website at View Source A replay of the call will be available shortly after completion of the call and will be archived on Puma’s website for 90 days.

About Puma Biotechnology

Puma Biotechnology, Inc. is a biopharmaceutical company with a focus on the development and commercialization of innovative products to enhance cancer care. Puma in-licenses the global development and commercialization rights to PB272 (neratinib, oral), PB272 (neratinib, intravenous) and PB357. Neratinib, oral was approved by the U.S. Food and Drug Administration in 2017 for the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, following adjuvant trastuzumab-based therapy, and is marketed in the United States as NERLYNX (neratinib) tablets. In February 2020, NERLYNX was also approved by the FDA in combination with capecitabine for the treatment of adult patients with advanced or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting. NERLYNX was granted marketing authorization by the European Commission in 2018 for the extended adjuvant treatment of adult patients with early stage hormone receptor-positive HER2-overexpressed/amplified breast cancer and who are less than one year from completion of prior adjuvant trastuzumab-based therapy. NERLYNX is a registered trademark of Puma Biotechnology, Inc.

Further information about Puma Biotechnology may be found at www.pumabiotechnology.com.

Important Safety Information Regarding NERLYNX (neratinib) U.S. Indication

NERLYNX (neratinib) tablets, for oral use

INDICATIONS AND USAGE: NERLYNX is a kinase inhibitor indicated:

As a single agent, for the extended adjuvant treatment of adult patients with early stage HER2-positive breast cancer, to follow adjuvant trastuzumab-based therapy.
In combination with capecitabine, for the treatment of adult patients with advanced or metastatic HER2-positive breast cancer, who have received two or more prior anti-HER2 based regimens in the metastatic setting.
CONTRAINDICATIONS: None

WARNINGS AND PRECAUTIONS:

Diarrhea: Manage diarrhea through either NERLYNX dose escalation or loperamide prophylaxis. If diarrhea occurs despite dose escalation or loperamide, treat with loperamide, additional antidiarrheals, fluids, and electrolytes as clinically indicated. Withhold NERLYNX in patients experiencing severe and/or persistent diarrhea. Permanently discontinue NERLYNX in patients experiencing Grade 4 diarrhea or Grade ≥ 2 diarrhea that occurs after maximal dose reduction.
Hepatotoxicity: Monitor liver function tests monthly for the first 3 months of treatment, then every 3 months while on treatment and as clinically indicated. Withhold NERLYNX in patients experiencing Grade 3 liver abnormalities and permanently discontinue NERLYNX in patients experiencing Grade 4 liver abnormalities.
Embryo-Fetal Toxicity: NERLYNX can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception.
ADVERSE REACTIONS:

The most common adverse reactions (reported in ≥ 5% of patients) were as follows:

NERLYNX as a single agent: Diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increased, nail disorder, dry skin, abdominal distention, epistaxis, weight decreased, and urinary tract infection.
NERLYNX in combination with capecitabine: Diarrhea, nausea, vomiting, decreased appetite, constipation, fatigue/asthenia, weight decreased, dizziness, back pain, arthralgia, urinary tract infection, upper respiratory tract infection, abdominal distention, renal impairment, and muscle spasms.
To report SUSPECTED ADVERSE REACTIONS, contact Puma Biotechnology, Inc. at 1-844-NERLYNX (1-844-637-5969) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS:

Gastric acid reducing agents: Avoid concomitant use with proton pump inhibitors. Separate NERLYNX by at least 3 hours with antacids. Separate NERLYNX by at least 2 hours before or 10 hours after H2-receptor antagonists. Or separate NERLYNX by at least 3 hours with antacids.
Strong CYP3A4 inhibitors: Avoid concomitant use.
P-gp and moderate CYP3A4 dual inhibitors: Avoid concomitant use.
Strong or moderate CYP3A4 inducers: Avoid concomitant use.
Certain P-gp substrates: Monitor for adverse reactions of P-gp substrates for which minimal concentration change may lead to serious adverse reactions when used concomitantly with NERLYNX.
USE IN SPECIFIC POPULATIONS:

Lactation: Advise women not to breastfeed.
Please see Full Prescribing Information for additional safety information.

To help ensure patients have access to NERLYNX, Puma has implemented the Puma Patient Lynx support program to assist patients and healthcare providers with reimbursement support and referrals to resources that can help with financial assistance. More information on the Puma Patient Lynx program can be found at www.NERLYNX.com or 1-855-816-5421.

On November 4, 2021 Nkarta, Inc. (Nasdaq: NKTX), a biopharmaceutical company developing engineered natural killer (NK) cell therapies to treat cancer, reported its participation at these upcoming investor conferences (Press release, Nkarta, NOV 4, 2021, View Source [SID1234594570]):

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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

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Cowen 5TH Annual IO Next Summit
November 15, 2021
11:15 a.m. ET – fireside chat presentation

Stifel 2021 Virtual Healthcare Conference
November 17, 2021
2:00 p.m. ET – fireside chat presentation

Evercore ISI 4TH Annual HealthCONx Conference
December 1, 2021
4:20 p.m. ET – fireside chat presentation

A simultaneous webcast of the presentations will be available on the Investors section of Nkarta’s website, www.nkartatx.com, and a replay will be archived on the website for approximately four weeks.

On November 4, 2021 Merus N.V. (Nasdaq: MRUS) ("Merus", the "Company," "we" and "our"), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics and Triclonics), reported the launch of a proposed underwritten public offering of its common shares (the "Offer Shares") (Press release, Merus, NOV 4, 2021, View Source [SID1234594600]). All of the common shares are being offered by Merus. In addition, Merus expects to grant the underwriters a 30-day option to purchase an additional 15% of the Offer Shares (the "Option Shares" and together with the Offer Shares, the "Shares"). The offering is subject to market conditions and other closing conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering.

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Merus intends to use the net proceeds from the offering to advance the clinical development of its product candidates, for preclinical research and technology development, and for working capital and general corporate purposes.

Jefferies LLC and SVB Leerink LLC are acting as joint book-running managers for the offering. Kempen & Co is acting as lead manager for the offering. H.C. Wainwright & Co. and Roth Capital Partners are acting as co-managers for the offering.

The offering will be made pursuant to a shelf registration statement on Form S-3 that was filed with the Securities and Exchange Commission ("SEC") on May 7, 2021 and was effective upon filing. The offering will be made only by means of a written prospectus and prospectus supplement that form a part of the registration statement, which, for the avoidance of doubt, will not constitute a "prospectus" for the purposes of (i) Regulation (EU) 2017/1129 (the "Prospectus Regulation") and has not been reviewed by any competent authority in any member state in the European Economic Area (the "EEA") and (ii) the Prospectus Regulation as it forms part of domestic law in the United Kingdom by virtue of the European Union (Withdrawal) Act 2018 (the "UK Prospectus Regulation") and has not been reviewed by the Financial Conduct Authority in the United Kingdom. A preliminary prospectus supplement and accompanying prospectus relating to the offering will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. Copies of the preliminary prospectus supplement and the accompanying prospectus relating to the offering may be obtained, when available, from Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY 10022, by phone at (877) 821-7388, or by email at [email protected] or SVB Leerink LLC, Attention: Syndicate Department, 53 State Street, 40th Floor, Boston, MA 02109, by telephone at (800) 808-7525, ext. 6105, or by email at [email protected].

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

This press release is an advertisement and not a prospectus within the meaning of either the Prospectus Regulation or the UK Prospectus Regulation.

EEA:

In relation to each member state of the EEA (each, a "Relevant State"), no Shares have been offered or will be offered pursuant to the offering to the public in that Relevant State, other than:

to any legal entity which is a qualified investor as defined under Article 2 of the Prospectus Regulation;
to fewer than 150 natural or legal persons (other than qualified investors as defined under Article 2 of the Prospectus Regulation), subject to obtaining the prior consent of the underwriters for any such offer; and
in any other circumstances falling within Article 1(4) of the Prospectus Regulation,
provided that no such offer of the Shares shall require us or any of our representatives to publish a prospectus pursuant to Article 3 of the Prospectus Regulation or supplement a prospectus pursuant to Article 23 of the Prospectus Regulation and each person who initially acquires any Shares or to whom any offer is made will be deemed to have represented, acknowledged and agreed to and with each of the representatives and us that it is a "qualified investor" as defined in the Prospectus Regulation.

For the purposes of the above, the expression an "offer of shares to the public" in relation to any Shares in any Relevant State means the communication in any form and by means of sufficient information on the terms of the offer and the Shares to be offered so as to enable an investor to decide to purchase Shares.

United Kingdom:

No Shares have been offered or will be offered pursuant to this offering to the public in the United Kingdom prior to the publication of a prospectus in relation to the Shares which has been approved by the Financial Conduct Authority, except that the Shares may be offered to the public in the United Kingdom at any time:

a) to any legal entity which is a qualified investor as defined under Article 2 of the UK Prospectus Regulation;

b) to fewer than 150 natural or legal persons (other than qualified investors as defined under Article 2 of the UK Prospectus Regulation), subject to obtaining the prior consent of the representatives for any such offer; or

c) in any other circumstances falling within Section 86 of the Financial Services and Markets Act 2000 (the "FSMA")

provided that no such offer of the Shares shall require us or any of our representatives to publish a prospectus pursuant to Section 85 of the FSMA or supplement a prospectus pursuant to Article 23 of the UK Prospectus Regulation.

For the purposes of this provision, the expression an "offer to the public" in relation to the Shares in the United Kingdom means the communication in any form and by any means of sufficient information on the terms of the offer and any Shares to be offered so as to enable an investor to decide to purchase or subscribe for any Shares.

In addition, in the United Kingdom, the transaction to which this press release relates will only be available to, and will be engaged in only with persons who are "qualified investors" (as defined in the UK Prospectus Regulation) (i) who have professional experience in matters relating to investments falling within Article 19(5) of the FSMA (Financial Promotion) Order 2005, as amended (the Order), and/or (ii) who are high net worth entities (or persons to whom it may otherwise be lawfully communicated) falling within Article 49(2)(a) to (d) of the Order (all such persons together being referred to as "relevant persons"). In the United Kingdom, the securities referred to herein are only available to, and any invitation, offer or agreement to subscribe, purchase or otherwise acquire such securities will be engaged in only with relevant persons. Any person in the United Kingdom who is not a relevant person should not act or rely on this communication or any of its contents.