On December 10, 2021 BeyondSpring Pharmaceuticals (the "Company" or "BeyondSpring") (NASDAQ: BYSI), a global pharmaceutical company focused on the development of cancer therapeutics, reported the presentation of additional analyses from the Phase 3 portion of the PROTECTIVE-2 trial evaluating the combination of plinabulin and pegfilgrastim for the prevention of chemotherapy-induced neutropenia (CIN) in breast cancer patients at the 2021 San Antonio Breast Cancer Symposium (SABCS), held both live and virtually from December 7-10, 2021 (Press release, BeyondSpring Pharmaceuticals, DEC 10, 2021, View Source;utm_medium=rss&utm_campaign=beyondspring-pharmaceuticals-announces-analysis-of-new-data-on-the-plinabulin-pegfilgrastim-combination-in-breast-cancer-at-the-2021-san-antonio-breast-cancer-symposium [SID1234596748]).

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"We’ve been able to demonstrate that adding plinabulin to pegfilgrastim significantly alleviates pegfilgrastim-related bone pain, decreases toxicity and improves health related quality-of-life (HrQoL) through new data analysis from the PROTECTIVE-2 study," said Dr. Douglas Blayney, professor of medicine at Stanford University Medical School and global principal investigator for the CIN studies. "With the superior CIN prevention benefit, the bone pain reduction benefit and quality of life benefit from adding plinabulin to pegfilgrastim, the TAC regimen (docetaxel, doxorubicin and cyclophosphamide) has the potential to become more tolerable in patients with breast cancer."

Dr. Ramon Mohanlal, executive vice president of research and development and chief medical officer at BeyondSpring Pharmaceuticals, added, "We’re pleased to be presenting at SABCS again this year and adding this new important data to our existing portfolio of CIN studies. Our goal has always been to create a better cancer treatment experience for these patients by alleviating some of the issues that can occur with CIN. We look forward to continuing to study how plinabulin can potentially make a difference in this indication."

The posters will be presented by Dr. Blayney during Poster Session 5 on Friday, December 10, 2021, from 8:00 AM to 9:30 AM EST and will be available on the SABCS website.

Poster Title: Mechanistic evidence associated with the benefit of plinabulin significantly reducing bone pain in breast cancer patients (pts) treated with TAC (docetaxel, doxorubicin, cyclophosphamide) and pegfilgrastim (Peg)
Publication Number: P5-18-01
Key Findings:

Patients treated with pegfilgrastim and plinabulin experienced less bone pain than did patients treated with pegfilgrastim only (p=0.03).
Treatment with plinabulin may mitigate the need for compensatory hematopoiesis and intracavitary pressure build-up, resulting in bone pain sensations.
Patients treated with pegfilgrastim and plinabulin had a higher absolute neutrophil count (ANC) at the nadir (the point of their lowest ANC).
Treatment-emergent adverse events of bone pain, cycles 1 to 4 (% of patients): TAC+Peg (30%) vs TAC+Peg+Plin (18%), p=0.03
ANC nadir during cycle 1 (mean ANC nadir (109 cells/L)): TAC+Peg (0.32) vs TAC+Peg+Plin (0.54), p=0.0002.
The depth of ANC nadir was statistically significantly correlated with bone pain scores; TAC+Peg vs TAC+Peg+Plin, p=0.019.
Poster Title: Combination plinabulin+pegfilgrastim (Plin+Peg) had better toxicity management and health related quality-of-life (HrQoL) compared to Peg alone in early-stage breast cancer (BC) patients (pts) treated with taxotere, doxorubicin and cyclophosphamide (TAC)
Publication Number: P5-18-04
Key Findings:

Adding plinabulin to pegfilgrastim decreases toxicity and improves HrQoL among patients with breast cancer receiving TAC. TAC should be reevaluated for patients with early-stage breast cancer in light of the improved outcomes seen with the addition of plinabulin and pegfilgrastim.
The adverse event (AE) profile among patients treated with plinabulin and pegfilgrastim was shifted towards lower grade AEs.
Adding plinabulin to pegfilgrastim prevented a decline in HrQoL scores for mobility, self-care, daily activities, pain and anxiety; significant change in EQ-5D-5L utility values, Cycles 1 to 4 for TAC+Peg vs TAC+Peg+Plin, p=0.024
About Plinabulin
Plinabulin, BeyondSpring’s lead asset, is a selective immunomodulating microtubule-binding agent (SIMBA), which is a potent antigen presenting cell (APC) inducer. It is a novel, intravenous infused, patent-protected asset for CIN prevention and a Phase 3 anti-cancer candidate for non-small cell lung cancer (NSCLC) with recently released positive topline data. Plinabulin triggers the release of the immune defense protein, GEF-H1, which leads to two distinct effects: first is a durable anticancer benefit due to the maturation of dendritic cells resulting in the activation of tumor antigen-specific T-cells to target cancer cells, and the second is early-onset of action in CIN prevention after chemotherapy by boosting the number of hematopoietic stem/progenitor cells (HSPCs). Plinabulin received Breakthrough Therapy designation from both U.S. and China FDA for the CIN prevention indication. As a "pipeline in a drug," plinabulin is being broadly studied in combination with various immuno-oncology agents that could boost the effects of the PD-1/PD-L1 antibodies and re-sensitize PD-1/PD-L1 antibody-resistant patients.

On December 10, 2021 Arvinas, Inc. (Nasdaq: ARVN) and Pfizer Inc. (NYSE: PFE) reported an update on Phase 1 dose escalation data of ARV-471, a novel PROTAC estrogen receptor (ER) degrader, which is being co-developed for the treatment of patients with locally advanced or metastatic ER-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer (ER+/HER2-) (Press release, Arvinas, DEC 10, 2021, View Source [SID1234596747]). These data were presented as a virtual spotlight poster session at the 2021 San Antonio Breast Cancer Symposium (SABCS) and showed:

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ARV-471 demonstrated antitumor activity in CDK4/6 inhibitor-pretreated patients with a clinical benefit rate (CBR) of 40% in 47 evaluable patients. This heavily pretreated patient group had a median of four prior therapies.
Three patients exhibited confirmed partial responses (PR) among the 38 patients with response evaluation criteria in solid tumors (RECIST) measurable lesions and at least one on-treatment tumor assessment.
ARV-471 continues to demonstrate a favorable tolerability profile. Robust ER degradation was observed at all dose levels, reaching 89% reduction of ER.
Erika P. Hamilton, MD, Director of the Breast Cancer and Gynecologic Cancer Research Program and Principal Investigator, Sarah Cannon Research Institute, provided an overview of these data.

"These results continue to suggest that ARV-471 has the potential to become a first-in-category treatment, and a new standard of care, for ER+/HER2- breast cancer patients," said John Houston, Ph.D., Chief Executive Officer at Arvinas. "The profile we see emerging for this drug candidate continues to validate our PROTAC protein degrader platform, with ARV-471 showing clear signals of clinical benefit in a heavily pretreated patient population, including tumor shrinkage and good tolerability."

These data support and further validate the evaluation of ARV-471 as a potential treatment for metastatic breast cancer that is ongoing in a Phase 1b combination study with IBRANCE (palbociclib) and a Phase 2 monotherapy dose expansion study.

"We are excited by these results and believe ARV-471 is a promising ER-targeting investigational medicine," said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. "It is encouraging to see ARV-471 continuing to show durable efficacy and tolerability in heavily pre-treated patients with ER+ breast cancer who have limited treatment choices."

ARV-471 Clinical Update

Enrollment

As of the data cut-off date of September 30, 2021, 60 adult patients with locally advanced or metastatic ER+/HER2- breast cancer were treated in the Phase 1 dose escalation portion of the study with total daily ARV-471 doses ranging from 30 mg to 700 mg. This patient group is heavily pretreated, with a median of four prior therapies. All patients were previously treated with cyclin-dependent kinase (CDK) 4/6 inhibitors; 80% of patients received prior fulvestrant; and 78% received prior chemotherapy.

Efficacy

Of 47 patients who were evaluable for clinical benefit (confirmed complete response, PR, or stable disease ≥ 24 weeks) the CBR was 40%. As of the data cutoff date, 14 patients were continuing to receive study treatment, including two patients who had been on treatment for over 18 months. Three confirmed PRs were observed among the 38 patients with baseline RECIST measurable disease and at least one on-treatment tumor assessment.

Safety

Patients were treated in the monotherapy escalation at total daily doses of 30 mg (n=3), 60 mg (n=3), 120 mg (n=7), 180/200 mg (n=11), 360 mg (n=15), 500 mg (n=17), and 700 mg (n= 4). All patients in the 700 mg cohort received ARV-471 twice-daily, a subset of patients who received 500 mg as a total daily dose received ARV-471 twice-daily, and other all doses were administered once-daily. A maximum tolerated dose was not reached and no dose limiting toxicities or Grade ≥4 treatment-related adverse events (TRAEs) were observed. Of the 60 patients, 37% had Grade 1 TRAEs and 57% had Grade ≤2 TRAEs, and the most common TRAEs were nausea (29%), fatigue (20%), and vomiting (10%). No Grade 1 or 2 TRAEs led to discontinuation or dose reduction of ARV-471. Four patients experienced six Grade 3 TRAEs that were potentially related to ARV-471, including: headache lasting 1-day, single occurrence of asymptomatic increased amylase and lipase, nausea and asymptomatic QTc prolongation, and post-biopsy venous embolism. The patient with the venous embolism was the only Grade 3 patient who discontinued ARV-471 due to a TRAE, and the patient with Grade 3 nausea was the only patient with a dose reduction due to a TRAE (reduced from 500 mg to 400 mg daily).

ER Degradation

In paired biopsies from 14 patients across all doses up to 500 mg daily, robust ER degradation of up to 89% was observed, regardless of ESR1 mutation status. Median and mean ER degradation across dose levels were 67% and 64%, respectively.

Pharmacokinetics

ARV-471 demonstrated a dose-related increase in plasma exposure, with doses from 30 mg to 500 mg daily, resulting in steady-state Cmax and AUC24 that exceeded the exposure associated with tumor regression in preclinical breast cancer models. Mean exposure on day 15 exceeded the nonclinical efficacious range at doses ≥60 mg daily.

Anticipated 2021/2022 Milestones

ARV-471 currently is being evaluated as a treatment for metastatic breast cancer in a Phase 1 dose escalation study, a Phase 1b combination study with IBRANCE (palbociclib), and a Phase 2 monotherapy dose expansion study.
In 2022, we expect to:
Initiate Phase 3 studies across lines of therapy in metastatic breast cancer, as both monotherapy and in combination.
Initiate two additional trials of ARV-471, including a Phase 1b combination trial with everolimus in 2L/3L metastatic breast cancer, potentially as part of a planned umbrella study to explore multiple combination agents, and a Phase 2 neoadjuvant trial in early breast cancer.
Present data from the ongoing Phase 1b combination study with IBRANCE (palbociclib) and from the ongoing Phase 2 monotherapy dose expansion study.
Investor Conference Call Details
Arvinas will host a conference call and webcast at 8:30 AM ET on Friday, December 10, 2021, to discuss these data. Pfizer Oncology executives will also participate in this call. Participants are invited to listen by dialing (844) 467-7654 (domestic) or (602) 563-8497 (international) five minutes prior to the start of the call and providing the passcode 9122219.

Supporting materials for the conference call and webcast will be available on the Arvinas’ website at www.arvinas.com under Events + Presentations. A replay of the webcast will be archived on the Arvinas website following the presentation.

About ARV-471
ARV-471 is an investigational orally bioavailable PROTAC protein degrader designed to specifically target and degrade the estrogen receptor (ER) for the treatment of patients with locally advanced or metastatic ER+/HER2- breast cancer.

In preclinical studies, ARV-471 demonstrated near-complete ER degradation in tumor cells, induced robust tumor shrinkage when dosed as a single agent in multiple ER-driven xenograft models, and showed superior anti-tumor activity when compared to a standard of care agent, fulvestrant, both as a single agent and in combination with a CDK4/6 inhibitor. In July 2021, Arvinas announced a global collaboration with Pfizer for the co-development and co-commercialization of ARV-471; Arvinas and Pfizer will equally share worldwide development costs, commercialization expenses, and profits.

On December 10, 2021 Abbott (NYSE: ABT) reported that its board of directors has increased the company’s quarterly common dividend, marking the company’s 50th consecutive year of dividend growth (Press release, Abbott, DEC 10, 2021, View Source [SID1234596746]).

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Abbott’s quarterly common dividend has been increased to 47 cents per share, a 4.4% increase that follows a 25% increase to the company’s quarterly dividend in 2021. It will be the 392nd consecutive quarterly dividend to be paid by Abbott since 1924. The cash dividend is payable Feb. 15, 2022, to shareholders of record at the close of business on Jan. 14, 2022.

Abbott is a member of the S&P 500 Dividend Aristocrats Index, which tracks companies that have increased dividends annually for at least 25 consecutive years.

"Fifty years of dividend growth reflects the consistently strong performance of our diversified business model," said Robert B. Ford, president and chief executive officer, Abbott. "It exemplifies our longstanding commitment to delivering sustainable growth that fuels innovation as well as shareholder returns."

Abbott’s board also has authorized the repurchase of up to $5 billion of the corporation’s common shares. This new authorization is in addition to the unused portion of the previous program authorized by Abbott’s board in October 2019. The purchases may be made from time to time as market conditions warrant and subject to regulatory considerations.

On December 10, 2021 Targovax ASA’s (the "Company") stock exchange reported that published on 30 November 2021 regarding the commencement of the subscription period in the rights issue of 101,744,186 new shares in the Company (the "Offer Shares") at a subscription price of NOK 1.72 per offer share (the "Rights Issue"), (Press release, Targovax, DEC 10, 2021, View Source [SID1234596744])

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The period for trading in subscription rights (ticker code "TRVXT") in the Rights Issue expires today, on 10 December 2021, at 16:30 hours (CET). Over-subscription and subscription without subscription rights are permitted.

The subscription period for the Rights Issue will expire at 16:30 hours (CET) on 14 December 2021.

Subscription rights that are not used to subscribe for Offer Shares before the expiry of the subscription period (14 December 2021 at 16:30 hours (CET)) or sold before 16:30 hours (CET) today, on 10 December 2021, will have no value and will lapse without compensation to the holder.

On December 10, 2021 Race Oncology Limited ("Race") reported it has extended and expanded its collaborative cardio-protective research program for Zantrene (bisantrene dihydrochloride) with eminent cardiotoxicity researchers, Associate Professors Aaron Sverdlov and Doan Ngo, at The University of Newcastle (Press release, Race Oncology, DEC 10, 2021, View Source [SID1234596742]).

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This collaboration builds on the initial heart safety preclinical study (ASX announcement: 28 April 2021) and will explore the cardio-protective attributes of Zantrene in vitro when used in combination with an expanded panel of anti-cancer drugs known to damage the hearts of cancer patients, as well as to undertake animal studies.

Race revealed an updated Three Pillar Strategy at the 2021 AGM (ASX Announcement: 23 November 2021) building on the recent discovery that Zantrene is able to protect heart muscle cells from both anthracycline and carfilzomib-induced death while also better targeting cancer cells (ASX announcements: 22 November 2021 & 08 December 2021).

This strategically important collaboration will underpin a cardio-protective Phase 2b clinical trial in cancer patients at high risk of anthracycline-induced heart damage, which is expected to begin treating patients in late 2022.

"The success of our collaboration with Associate Professors Aaron Sverdlov and Doan Ngo has been exceptional to date. We all look forward to uncovering all the cardio-protection secrets Zantrene has to reveal."

Chief Scientific Officer, Dr Daniel Tillett
This program will cost $322K and start immediately, with results to be reported over the coming 12 months.