Nektar Therapeutics Announces Initiation of First-in-Human Phase 1 Clinical Study of NKTR-255, an IL-15 Agonist, in Adults with Relapsed or Refractory Non-Hodgkin Lymphoma or Multiple Myeloma

On October 16, 2019 Nektar Therapeutics (NASDAQ: NKTR) reported the initiation of a first-in-human, Phase 1 clinical study evaluating NKTR-255, an interleukin-15 (IL-15) receptor agonist, as monotherapy for patients with relapsed or refractory non-Hodgkin lymphoma (NHL) or multiple myeloma (MM) (Press release, Nektar Therapeutics, OCT 16, 2019, View Source [SID1234542320]). The study will also combine NKTR-255 with multiple targeted antibodies, that function through an antibody-dependent cell-mediated cytotoxicity (ADCC) mechanism, to evaluate the safety and efficacy in adults with relapsed or refractory MM. NKTR-255 is designed to activate the IL-15 pathway and expand functionally superior natural killer (NK) cells and promote the survival and expansion of memory CD8+ T cells without inducing suppressive regulatory T cells.

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"We are excited to launch the first-in-human clinical study of NKTR-255, which has shown promising and substantial anti-tumor activity in our preclinical studies," said Wei Lin, M.D., Senior Vice President and Head of Development at Nektar Therapeutics. "By increasing the number and activity of NK cells, NKTR-255 has the potential to enhance the host’s tumor-fighting response, both as a single agent and in combination with tumor-targeting antibodies, including daratumumab and rituximab."

One of the big challenges in treating cancer patients with targeted monoclonal antibodies is that the cancer patients have a deficiency in key effector cells like NK cells that are needed to work with the monoclonal antibodies.1,2 In nonclinical studies, NKTR-255 exhibited anti-tumor activity and substantially enhanced in vivo proliferation and activation of NK cells to provide sustained cytotoxic function.3 In a preclinical lymphoma model where single agent daratumumab was ineffective, NKTR-255 treatment, in combination with daratumumab, increased NK cell numbers and activity in bone marrow tissue and enhanced ADCC-mediated tumor cell clearance in the bone marrow compartment.4

NHL is one of the most common cancers in the United States, accounting for about 4% of all cancers. The American Cancer Society estimates that in 2019, approximately 74,200 people will be diagnosed with NHL in the U.S. and about 19,970 will die from this cancer. MM is a relatively uncommon cancer in the U.S., with a lifetime risk of getting MM of 1 in 132 (0.76%). The American Cancer Society estimates that in 2019, approximately 32,110 people will be diagnosed with MM and about 12,960 will die from this disease.

About the NKTR-255 Phase 1 Study
The NKTR-255 Phase 1 study is an open-label, dose escalation and dose expansion study in patients with select hematological malignancies (relapsed or refractory NHL or MM). The dose escalation phase of the study will evaluate the safety and tolerability of NKTR-255 as monotherapy in approximately 40 patients in order to establish a recommended Phase 2 dose (RP2D) for NKTR-255. The dose expansion phase of the study will enroll in two separate cohorts: the first cohort will enroll patients with MM or NHL (relapsed salvage) to evaluate the NKTR-255 RP2D as a monotherapy and the second cohort will enroll patients with MM or NHL (relapsed/refractory salvage) to evaluate the NKTR-255 RP2D in combination with targeted antibodies, including anti-CD38 monoclonal antibody, daratumumab. The study will also evaluate pharmacokinetic and pharmacodynamic effects, anti-tumor activity and biomarker assessments.

About NKTR-255
NKTR-255 is an IL-15 receptor agonist designed to activate the IL-15 pathway and expand NK cells and promote the survival and expansion of memory CD8+ T cells without inducing suppressive regulatory T cells. Through optimal engagement of the IL-15Rα/IL-2Rβγ receptor complex, NKTR-255 enhances formation of long-term immunological memory, which may lead to sustained anti-tumor immune response. NKTR-255 is uniquely designed to overcome the challenges of recombinant IL-15, which is rapidly cleared from the body and must be administered frequently and in high doses, limiting its utility due to toxicity and convenience of use.

Sutro Biopharma Announces Presentation of STRO-002 for the Potential Treatment of Ovarian and Endometrial Cancer at the 2019 AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics Conference

On Octobber 16, 2019 Sutro Biopharma, Inc. (NASDAQ: STRO) reported that the company will present at the upcoming AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) being held Oct. 26-30, 2019, in Boston (Press release, Sutro Biopharma, OCT 16, 2019, View Source [SID1234542305]). The presentation will include both new preclinical efficacy data and initial dose escalation safety data from the company’s ongoing Phase I study of STRO-002 in patients with ovarian cancer. STRO-002 is a novel antibody-drug conjugate (ADC) targeting the clinically validated folate receptor-α (FRα), an antigen known to be overexpressed in ovarian cancer. Sutro discovered and manufactures STRO-002 using its proprietary XpressCF+ cell-free protein synthesis technology.

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Poster Presentation Details:

Antitumor activity of STRO-002, a novel folate receptor-α (FRα) antibody drug conjugate (ADC), in patient-derived xenograft (PDX) models and preliminary phase I dose escalation safety outcomes in patients with ovarian carcinoma (OC)

Date: Tuesday, Oct. 29, 2019

Time: 12:30 p.m. – 4:00 p.m. EDT

Location: Hall D, Hynes Convention Center, Boston, MA, United States

Poster Session: Tubulin-interacting Agents

Abstract Number: C095

The abstract was published today on the AACR (Free AACR Whitepaper) website. The poster will be accessible through the Clinical/Scientific Presentation and Publication Highlights page of the News section of the company’s website at www.sutrobio.com on the day of the poster presentation.

Enzychem Lifesciences Announces Three Abstracts Accepted at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics

On October 16, 2019 Enzychem Lifesciences, a leading global biopharmaceutical company focusing on innovative new drug development for unmet medical needs, reported that three abstracts have been accepted for poster presentation at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper), on October 26-30, 2019, at the Hynes Convention Center in Boston, Massachusetts (Press release, Enzychem Lifesciences, OCT 16, 2019, View Source [SID1234542321]).

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This new data demonstrates Enzychem Lifesciences’ commitment to fully understanding of EC-18’s mechanism of action on transendothelial migration & tissue infiltration of neutrophils, as well as potential antitumor effects of EC-18 in the therapeutic indications.

"Tumor infiltrating neutrophils play an important role in tumor progression and metastasis. There is a great need for developing a drug such as EC-18 that may reduce tumor metastasis through novel mechanism of modulating neutrophil trafficking," said Dr. Jeff Crawford, Chairperson of scientific advisory board of Enzychem Lifesciences.

Poster presentation details:

Title: A phase 1/2a, open-label, dose-escalation study of EC-18 in patients with metastatic breast cancer for the prevention of chemotherapy-induced neutropenia

Abstract: A070

Date/Time: Sunday Oct 27, 12:30pm – 4:00 pm

Location: Board 70

Title: The synergistic effect of PLAG on the antitumor efficacy of AC-regimen via alleviating neutrophil tumor infiltration on breast tumor xenograft model

Abstract Number: B054

Date/Time: Monday Oct 28, 12:30pm – 4:00pm

Location: Board 54

Title: Anti-metastatic effect of PLAG via interference of neutrophil elastase/PAR2/EGFR signaling on A549 lung cancer orthotopic implantation model

Abstract Number: C037

Date/Time: Tuesday Oct 29, 12:30pm – 4:00 pm

Location: Board 37

4SC and Netherlands Cancer Institute Collaborate on Clinical Evaluation of Domatinostat in the Neoadjuvant Setting in Melanoma

On October 16, 2019 4SC AG (4SC, FSE Prime Standard: VSC) reported a collaboration with the Netherlands Cancer Institute (Stichting Het Nederlands Kanker Instituut (NKI) – Antoni van Leeuwenhoek Ziekenhuis) in Amsterdam to evaluate domatinostat in combination with checkpoint blockade in a "Multicenter Phase 1b Study testing the Neoadjuvant Combination of Domatinostat, Nivolumab, and Ipilimumab, in RECIST 1.1-measurable Stage III Cutaneous or Unknown Primary Melanoma – DONIMI" (Press release, 4SC, OCT 16, 2019, View Source [SID1234542306]).

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Immunotherapy, and particularly checkpoint inhibitors like anti-PD-1 (e.g. Nivolumab) and anti-CTLA4 (Ipilimumab), are increasingly investigated not only in the advanced unresectable or metastatic setting but also in earlier stages of disease. The rationale for such treatment is to activate the immune system before resection of the tumor to generate an immune memory and prevent recurrence of the disease. On the basis of some encouraging data published by the International Neoadjuvant Melanoma Consortium (INMC; View Source), innovative combination approaches will now be tested to optimize the treatment in a more personalized manner where domatinostat is a promising combination partner.

Jason Loveridge, Ph.D., CEO of 4SC: "It is getting clearer and clearer that immunotherapy for cancer is most effective when used early in disease progression and we believe the neoadjuvant setting offers a great potential for protecting patients from recurrence of their malignancy after resection, potentially leading to a much higher number of cured patients with resectable, high-risk melanoma. Prof. Blank and his collaborators within the INMC have already made remarkable progress in this highly innovative field in melanoma and the NKI is a worldwide leading cancer center in the treatment of melanoma and other indications in the neoadjuvant setting. We are grateful entering such collaboration with the NKI and looking forward to the initiation of the DONIMI study in the near future."

Prof. Dr. Christian Blank, NKI: "It is exciting to see what we have achieved with neoadjuvant immunotherapy in melanoma within the INMC during the last few years. However there´s still a way to go to implement a standard neoadjuvant treatment in melanoma. Additional combination approaches to modulate the tumor microenvironment and the patients´ immune system remains a priority so as to optimize and personalize treatment for patients with melanoma, and potentially impact the treatment of patients with other cancers. For example, we do not know yet which patients require double neoadjuvant checkpoint inhibition and who can be treated with neoadjuvant PD-1 blockade alone. Based on preclinical and early clinical data, epigenetic modulation with domatinostat in combination with checkpoint blockade might be a promising approach in the neoadjuvant setting. In the DONIMI study, Domatinostat will be one of the first compounds tested in a personalized neoadjuvant combination trial implemented by INMC researchers from Sydney and Amsterdam. We are much looking forward to enroll the first patients later this year."

Abbott Reports Third-Quarter 2019 Results

On October 16, 2019 Abbott (NYSE: ABT) reported financial results for the third quarter ended Sept. 30, 2019 (Press release, Abbott, OCT 16, 2019, View Source [SID1234542323]).

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Third-quarter worldwide sales of $8.1 billion increased 5.5 percent on a reported basis and 7.6 percent on an organic* basis.
Reported diluted EPS from continuing operations under GAAP was $0.53 in the third quarter. Adjusted diluted EPS from continuing operations, which excludes specified items, was $0.84, an increase of 12.0 percent versus prior year1.
Abbott narrowed its full-year 2019 outlook for diluted EPS from continuing operations on a GAAP basis to $2.06 to $2.08, and full-year adjusted diluted EPS from continuing operations to $3.23 to $3.25, reflecting 12.5 percent growth versus the prior year at the midpoint of the range2.
FreeStyle Libre achieved worldwide sales of $496 million in the quarter, an increase of 63.1 percent on a reported basis and 67.6 percent on an organic basis versus the prior year.
During the third quarter, FreeStyle Libre obtained public reimbursement coverage in Ontario and Quebec, becoming the first and only sensor-based glucose monitoring system to be listed by any provincial health plan in Canada.
Worldwide sales of MitraClip were $176 million in the quarter, an increase of 30.4 percent on a reported basis and 31.9 percent on an organic basis, including U.S. growth of 45.7 percent versus the prior year. During the third quarter, Abbott announced U.S. FDA approval of its next-generation MitraClip device, which offers enhancements and more sizes to offer doctors further options.
In September, Abbott announced data from its COAPT Trial that shows that MitraClip is projected to increase life-expectancy and quality of life compared to guideline-directed medical therapy alone in heart failure patients with secondary mitral regurgitation, or a leaky mitral heart valve.
During the third quarter, Abbott received U.S. FDA approval for its Alinity-S diagnostics system, the latest technology for screening and protecting the U.S. blood and plasma supply.
"We’re performing exceptionally well across several areas," said Miles D. White, chairman and chief executive officer, Abbott. "We’re right on track to achieve ongoing EPS and organic sales growth at the upper-end of our initial guidance ranges for the year."

* See note on organic growth below.

THIRD-QUARTER BUSINESS OVERVIEW
Note: Management believes that measuring sales growth rates on an organic basis is an appropriate way for investors to best understand the underlying performance of the business.

Organic sales growth:

Excludes the prior year first, second and third-quarter results for a non-core business within U.S. Adult Nutrition, which was discontinued during the third quarter 2018; and
Excludes the impact of foreign exchange.

Third-quarter 2019 worldwide sales of $8.1 billion increased 5.5 percent on a reported basis. On an organic basis, worldwide sales increased 7.6 percent. Refer to tables titled "Non-GAAP Reconciliation of Adjusted Historical Revenue" for a reconciliation of adjusted historical revenue.

Worldwide Nutrition sales increased 2.0 percent on a reported basis in the third quarter. On an organic basis, sales increased 3.8 percent. Refer to tables titled "Non-GAAP Reconciliation of Adjusted Historical Revenue" for a reconciliation of adjusted historical revenue.

Worldwide Pediatric Nutrition sales increased 0.5 percent on a reported basis in the third quarter, including an unfavorable 0.9 percent effect of foreign exchange, and increased 1.4 percent on an organic basis. In the U.S., sales growth was led by Abbott’s market-leading toddler brands, PediaSure and Pedialyte. International sales declined 2.4 percent on a reported basis and 0.7 percent on an organic basis, driven by challenging market dynamics in Greater China, partially offset by growth across several countries in Southeast Asia and Latin America.

Worldwide Adult Nutrition sales increased 3.9 percent on a reported basis in the third quarter and increased 6.9 percent on an organic basis. International Adult Nutrition sales increased 7.5 percent on a reported basis and 10.4 percent on an organic basis in the third quarter. Sales performance in the quarter was led by strong growth of Ensure, Abbott’s market-leading complete and balanced nutrition brand, and Glucerna, Abbott’s market-leading diabetes-specific nutrition brand.

Worldwide Diagnostics sales increased 4.7 percent on a reported basis in the third quarter, including an unfavorable 1.9 percent effect of foreign exchange, and increased 6.6 percent on an organic basis.

Core Laboratory Diagnostics sales increased 8.3 percent on a reported basis and 10.6 percent on an organic basis in the third quarter. Sales performance was led by above-market growth in the U.S. and internationally, where Abbott is achieving continued strong adoption of its Alinity family of innovative and highly differentiated diagnostic instruments. During the third quarter, Abbott received U.S. FDA approval for its Alinity-S blood and plasma screening diagnostics instrument and several testing assays.

Molecular Diagnostics sales decreased 7.8 percent on a reported basis in the third quarter, including an unfavorable 1.4 percent effect of foreign exchange, and decreased 6.4 percent on an organic basis. Internationally, sales growth in the quarter was negatively impacted by lower non-governmental organization purchases in Africa.

Point of Care Diagnostics sales increased 6.3 percent on a reported basis in the third quarter, including an unfavorable 0.4 percent effect of foreign exchange, and increased 6.7 percent on an organic basis. Sales growth was led by Abbott’s market-leading i-STAT handheld system in the U.S. and internationally.

Rapid Diagnostics sales decreased 0.7 percent on a reported basis in the third quarter, including an unfavorable 1.5 percent effect of foreign exchange, and increased 0.8 percent on an organic basis. Organic sales growth was led by infectious disease testing in developed markets and cardio-metabolic testing globally, partially offset by lower than expected infectious disease testing sales in Africa.

Established Pharmaceuticals sales increased 4.4 percent on a reported basis in the third quarter, including an unfavorable 3.5 percent effect of foreign exchange, and increased 7.9 percent on an organic basis.

Key Emerging Markets include India, Brazil, Russia and China along with several additional emerging countries that represent the most attractive long-term growth opportunities for Abbott’s branded generics product portfolio. Sales in these geographies increased 2.8 percent on a reported basis in the third quarter and increased 6.8 percent on an organic basis, which excludes an unfavorable 4.0 percent effect of foreign exchange. Organic sales growth was led by strong growth across several geographies, including India, China and Brazil.

Other sales increased 9.2 percent on a reported basis in the third quarter, including an unfavorable 1.7 percent effect of foreign exchange, and increased 10.9 percent on an organic basis.

Worldwide Medical Devices sales increased 8.9 percent on a reported basis in the third quarter and increased 10.6 percent on an organic basis, led by double-digit growth in Electrophysiology, Heart Failure, Structural Heart and Diabetes Care.

In Electrophysiology, growth was led by strong performance in cardiac diagnostic and ablation catheters, which are used to help physicians accurately and effectively treat atrial fibrillation, a form of irregular heartbeat.

In Heart Failure, strong double-digit growth was driven by market adoption of Abbott’s HeartMate 3 left ventricular assist device, which has been shown to improve survival and clinical outcomes in patients with advanced heart failure.

Growth in Structural Heart was led by MitraClip, Abbott’s market-leading device for the minimally invasive treatment of mitral regurgitation, or a leaky mitral heart valve. In the third quarter, Abbott announced U.S. FDA approval of its next-generation MitraClip device, MitraClip G4, which offers an expanded range of clip sizes, an alternative leaflet grasping feature and facilitation of procedure assessment in real time to offer doctors further options when treating mitral valve disease.

In Diabetes Care, sales increased 29.6 percent on a reported basis and 33.1 percent on an organic basis in the third quarter. Sales growth in the quarter was led by FreeStyle Libre, Abbott’s revolutionary continuous glucose monitoring system, with worldwide sales of $496 million, an increase of 63.1 percent on a reported basis and 67.6 percent on an organic basis versus the prior year. During the third quarter, FreeStyle Libre obtained public reimbursement coverage in Ontario and Quebec, becoming the first and only sensor-based glucose monitoring system to be listed by any provincial health plan in Canada.

ABBOTT’S GUIDANCE FOR 2019
Abbott is narrowing its guidance for 2019 diluted earnings per share from continuing operations under Generally Accepted Accounting Principles (GAAP) to $2.06 to $2.08. Abbott forecasts net specified items for the full year 2019 of $1.17 per share. Specified items include intangible amortization expense, acquisition-related expenses, charges associated with cost reduction initiatives and other expenses. Excluding specified items, projected adjusted diluted earnings per share from continuing operations would be $3.23 to $3.25 for the full year 2019.

Abbott is issuing fourth-quarter 2019 guidance for diluted earnings per share from continuing operations under GAAP of $0.59 to $0.61. Abbott forecasts specified items for the fourth quarter 2019 of $0.35 per share primarily related to intangible amortization, acquisition-related expenses, cost reduction initiatives and other expenses. Excluding specified items, projected adjusted diluted earnings per share from continuing operations would be $0.94 to $0.96 for the fourth quarter.

ABBOTT DECLARES 383RD CONSECUTIVE QUARTERLY DIVIDEND
On Sept. 12, 2019, the board of directors of Abbott declared the company’s quarterly dividend of $0.32 per share. Abbott’s cash dividend is payable Nov. 15, 2019, to shareholders of record at the close of business on Oct. 15, 2019.

Abbott has increased its dividend payout for 47 consecutive years and is a member of the S&P 500 Dividend Aristocrats Index, which tracks companies that have annually increased their dividend for at least 25 consecutive years.