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Daiichi Sankyo Announces Share Split, Partial Amendment to the Articles of Incorporation, and Forecast of Annual Dividend per Share for the Year Ending March 31, 2021

On April 27, 2020 Daiichi Sankyo Company, Limited (hereafter "Daiichi Sankyo") reported that Daiichi Sankyo has resolved, at the Board of Directors meeting held , a share split, a partial amendment to the articles of incorporation, and the forecast of annual dividend per share for the year ending March 31, 2021 (from April 1, 2020 to March 31, 2021) (Press release, Daiichi Sankyo, APR 27, 2020, View Source [SID1234556609]).

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1. Purpose of the share split

The share split aims to increase the liquidity of the shares by reducing the investment unit price for Daiichi Sankyo’s share, and to further expand the investor base.

2. Outline of the share split

(1) Method

Fixing Wednesday, September 30, 2020 as the record date, Daiichi Sankyo will split its ordinary shares, owned by the shareholders listed or recorded in the shareholder registry, three-for-one.

(2) Number of shares to be increased by the share split

① Total number of shares issued before the share split

709,011,343

② Increase in the number of shares upon the share split

1,418,022,686

③ Total number of shares issued after the share split

2,127,034,029

④ Total number of shares issuable after the share split

8,400,000,000

(3) Schedule

① Announcement of record date

Friday, September 11, 2020

② Record date

Wednesday, September 30, 2020

③ Effective date

Thursday, October 1, 2020

(4) Others

The share split will not change the amount of stated capital

3. Partial amendment to the articles of incorporation

(1) Reason for the amendment

In line with the share split, pursuant to the Article 184.2 of the Companies Act of Japan, Daiichi Sankyo will amend, as of Thursday, October 1, 2020, the total number of shares issuable set by Article 6 in the Articles of Incorporation of Daiichi Sankyo.

(2) Details of the amendment to the articles of incorporation

Details are as follows.

（Underlined points indicate changes）

Before the amendment

After the amendment

　(Total Number of Shares Issuable)
　Article 6. The total number of shares issuable by the Company shall be 2.8 billion shares.

　(Total Number of Shares Issuable)
　Article 6. The total number of shares issuable by the Company shall be 8.4 billion shares.

(3) Schedule for the amendment to the articles of incorporation

Date resolved at the Board of Directors meeting 　　: Monday, April 27, 2020

Effective date of the amendment to the articles of incorporation: Thursday, October 1, 2020

4. Forecast of annual dividend per share for the year ending March 31, 2021

In order to secure sustainable growth in corporate value, one of the fundamental business policies for Daiichi Sankyo is to decide profit distribution based on comprehensive consideration around the investments essential for implementing its growth strategies, and returning profits to its shareholders.In the current 5-year Business Plan, Daiichi Sankyo introduced a total return ratio* of 100% or more from fiscal year 2016 to fiscal year 2022, and in terms of dividend payments, to distribute annual dividend per share of 70 yen or more.

Now, Daiichi Sankyo has decided to increase the forecast of annual dividend per share for the year ending March 31, 2021 in order to further strengthen shareholder return.

As stated above, since Daiichi Sankyo will carry out a share split at a ratio of three-for-one on Thursday, October 1, 2020 as the effective date, the forecast of annual dividend per share for the year ending March 31, 2021 is 40.50 yen per ordinary share before the split at the end of second quarter, and 13.50 yen per ordinary share after the split at fiscal year-end.

The forecast of annual dividend per share shows the pre-split amount since it cannot be simply compared with the fiscal year which ended on March 31, 2020 due to the implementation of the share split and the end of second quarter dividend will be 40.50 yen per share. Therefore, the annual dividend per share is forecasted to be 81 yen (pre-split standard).

As a result, the annual dividend per share (pre-split standard) is expected to practically increase by 11 yen.

Alligator Bioscience Presents Promising Interim Phase I Data for its Bispecific Drug Candidate ATOR-1015 at AACR

On April 27, 2020 Alligator Bioscience (Nasdaq Stockholm: ATORX), reported that the company presents the status of the ongoing Phase I clinical trial with the bispecific drug candidate ATOR-1015 developed as tumor-directed therapy for metastatic cancer (Press release, Alligator Bioscience, APR 27, 2020, View Source [SID1234556607]). The presentation will take place at the AACR (Free AACR Whitepaper) (American Association for Cancer Research) Annual Meeting, which this year is being held digital for the first time.

This far, doses of 400 mg (about 6 mg/kg) have been evaluated in the ongoing study and the current dosing is 600 mg (about 10 mg/kg). 18 patients with varying cancer forms (colon cancer, eye melanoma, pancreatic cancer, ovarian cancer, gallbladder cancer, gastric cancer and skin cancer) have been treated and evaluated in terms of safety. ATOR-1015 has so far been well tolerated.

"We are very proud and happy that our study has been selected for presentation. The promising results so far demonstrate that ATOR-1015 can be administered safely. ATOR-1015 has the potential to be at least as effective as today’s available treatment for these patients, but with significantly fewer side effects," said Per Norlén, CEO of Alligator Bioscience.

The adverse events in the study were generally mild and transient, all of grade 1 or 2 (on a scale of 1-5). The most common adverse events were infusion-related reactions (five patients). No serious immune-related or dose-limiting adverse events have been reported.

The presentation with the title "A first-in-human phase 1 study in patients with advanced and/or refractory solid malignancies to evaluate the safety of ATOR-1015, a CTLA-4 x OX40 bispecific antibody" will be held by Charlotte Russell, Chief Medical Officer at Alligator Bioscience. The presentation is available through the link below between 9:00 a.m. – 6:00 p.m. EDT (3 p.m.-12 a.m. CEST) today and will also be available on the company website www.alligatorbioscience.com. View Source!/9045/presentation/10644

About the ATOR-1015 Phase I study
The Phase I study with ATOR-1015 is a dose escalation study in patients with metastatic cancer (NCT03782467). The primary endpoint of the study is to investigate the safety and tolerability of ATOR-1015 and to determine the recommended dose for subsequent Phase II studies. The first patient was dosed in March 2019 and results are expected during the second half of 2020. Following the establishment of the maximum tolerable dose or recommended dose for Phase II, further clinical development of ATOR-1015 is planned, primarily for the treatment of metastatic skin cancer.

Due to the Covid-19 pandemic, most, but not all, participating clinics have made a temporary halt in the recruitment of new patients. Alligator Bioscience is in close dialogue with all parties in order to resume patient recruitment at full speed as soon as possible. The company follows the clinics’ decisions and evaluates appropriate measures to minimize any delays. At this stage, it is too early to estimate whether the slower recruitment will affect the timeline for 2020 and for the longer term.

About ATOR-1015
ATOR-1015, wholly owned by Alligator, is a bispecific CTLA-4 antibody developed as tumor targeted immunotherapy with increased capacity for killing regulatory T cells. ATOR-1015 binds to two different immune receptors – the checkpoint receptor CTLA-4 and the co-stimulatory receptor OX40. The immune activation is increased in areas where both target molecules are expressed at high levels, notably in the tumor microenvironment, which can lead to reduced side effects.

Sutro Biopharma Announces Encouraging Interim Phase 1 Clinical Data for a Dose Escalation Study of STRO-002 Antibody-Drug Conjugate in Ovarian Cancer

On April 27, 2020 Sutro Biopharma, Inc. (NASDAQ: STRO), a clinical-stage drug discovery, development and manufacturing company focused on the application of precise protein engineering and rational design to create next-generation oncology therapeutics, reported updated interim data regarding safety and anti-tumor activity results in heavily pre-treated patients with ovarian cancer from its on-going Phase 1 clinical trial (dose escalation phase) evaluating its folate receptor alpha (FolRα) antibody drug-conjugate (ADC) STRO-002 (Press release, Sutro Biopharma, APR 27, 2020, View Source [SID1234556606]). Sutro will host a conference call and live audio webcast on Monday, April 27, at 8 a.m. EDT to discuss the STRO-002 data.

"We designed STRO-002 to have a wider therapeutic window, with the potential for improved tumor control and better patient tolerability, than other FolRα targeted therapies," said Bill Newell, CEO of Sutro Biopharma. "The data we present today from this all-comers trial suggest that our optimally designed ADC can achieve these objectives. In 75% (15 of 20) of ovarian cancer patients at STRO-002 dose levels of 2.9 milligrams per kilogram (mpk) or higher, we saw in the initial post-baseline scans one partial response and 14 stable disease. This level of tumor control is typically very difficult to achieve in these patients who have been heavily pre-treated, with a median of five prior lines of other therapies, and who have such advanced disease. Equally encouraging are the data showing that 13 patients had a ≥50% reduction or normalization of CA-125, including six confirmed responses, six unconfirmed responses and one prolonged CA-125 normalization. Of these 13 patients, one patient is not yet evaluable under RECIST criteria. All of the other 12 patients (100%) have also achieved stable disease (confirmed or unconfirmed) or a confirmed partial response. With 89% of adverse events (AEs) reported to be grade 1 or 2, we believe the emerging safety profile reflects our optimized design approach."

The interim clinical data for STRO-002 in patients treated at dose levels of 2.9 mpk or higher include: one patient with an ongoing confirmed partial response (36 weeks); five patients with confirmed stable disease (three up to 18 weeks, two up to 27 weeks); and seven ongoing patients who have unconfirmed stable disease at the six-week assessment point.

STRO-002 was generally well-tolerated and was mostly associated with mild AEs. Eighty-nine percent (89%) of AEs were grade 1 or grade 2 and prophylactic corticosteroid eye drops have not been necessary. Grade 3 treatment emergent AEs included fatigue, neutropenia, arthralgia, diarrhea, peripheral neuropathy and myalgia, with the only grade 4 treatment emergent AE being neutropenia; all neutropenias were reversible within one week.

"The preliminary evidence of anti-tumor activity we observed is encouraging, particularly in this heavily pre-treated patient population," said Wendel Naumann, MD, gynecologic oncologist at Levine Cancer Institute and a principal investigator on the STRO-002 study. "With limited therapeutic options for these patients, we are excited to continue to advance this clinical program to further investigate its therapeutic potential."

"These data support Sutro’s continued development of targeted therapies for cancer patients and joins two other Sutro-developed and manufactured ADCs in clinical trials, including our BCMA-targeted ADC which is in a Phase 1 trial being conducted by our collaborator Bristol Myers Squibb," said Arturo Molina, MD, Sutro’s Chief Medical Officer. "It is extremely encouraging that we see this preliminary evidence of anti-tumor activity at this stage of development. As we advance STRO-002 in the clinic, we plan to share additional data on the efficacy and safety of STRO-002 by the end of 2020 and we look forward to the potential to bring a new treatment option to ovarian cancer patients."

Through April 20, 2020, the Phase 1 trial of STRO-002 has enrolled 30 patients with recurrent platinum resistant or refractory ovarian cancer, without regard to FolRα expression levels. A dose expansion phase of this trial is planned to commence in the second half of 2020. Although maximum tolerated dose (MTD) has not been reached, Sutro is continuing to actively explore the 5.2 mpk to 6.0 mpk dose levels as it seeks to determine the recommended Phase 2 dose.

The ongoing Phase 1, open-label, multicenter, dose escalation trial with dose expansion of STRO-002 is designed to identify the MTD, the recommended Phase 2 clinical dose and to evaluate the safety, tolerability, and preliminary anti-tumor activity of STRO-002 in adults with advanced epithelial ovarian cancer, including fallopian or primary peritoneal cancer, and endometrial cancer. This trial is registered with clinicaltrials.gov identifier NCT03748186. Sutro discovered, developed and manufactures STRO-002 using its proprietary XpressCF+ cell-free protein synthesis technology.

Conference Call Information:

To access the conference call and live audio webcast on Monday, April 27, at 8 a.m. EDT, please dial (833) 729-4781 (domestic) or (830) 213-7705 (international) and refer to conference ID 2699785.

The conference call will be webcast via the Investors page on the company’s website at ir.sutrobio.com. Approximately two hours following the live event, a webcast replay of the conference call will be available through the Company Presentation page of the Investor section of the company’s website at www.sutrobio.com for approximately 30 days.

Poster Presentation Details:

STRO-002-GM1, a First in Human, Phase 1 Study of STRO-002, an anti-Folate Receptor-alpha (FRα) Antibody Drug Conjugate (ADC), in Patients with Advanced Platinum-Resistant/Refractory Epithelial Ovarian Cancer (OC), including Fallopian Tube or Primary Peritoneal Cancers

Date & Time:

Monday, April 27, 2020, 9 a.m. to 6 p.m. EDT

Location:

The AACR (Free AACR Whitepaper) Virtual Meeting at aacr.org

Poster Number:

CT125

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.

I-SPY2 TRIAL Demonstrates Significant Improvement in pCR with Durvalumab and Olaparib with Paclitaxel, (Compared to Chemotherapy Alone) in Women with Stage II/III High-Risk, HER2-Negative Breast Cancer, in HR+ and TNBC Subsets

On April 27, 2020 I-SPY 2 TRIAL reported that results on April 27 at the clinical trial plenary session of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2020 annual meeting, which showed that adding the immune checkpoint inhibitor durvalumab and the PARP inhibitor olaparib to standard of care pre-operative (neoadjuvant) chemotherapy improved outcomes for women with stage II/III, high-risk, HER2-Negative Breast Cancer (Press release, I-SPY 2 TRIAL, APR 27, 2020, View Source [SID1234556605]). Patients who received durvalumab + olaparib + paclitaxel (DOP) followed by doxorubicin/cyclophosphamide (AC), achieved complete eradication of their cancer from the breast and axillary lymph nodes at the time of surgery (i.e pathologic complete response) at a greater rate than patients treated with chemotherapy alone (37% versus 20%). This degree of response met the threshold for graduation, meaning that there is a greater than 85% predicted probability of success if this combination was tested against standard chemotherapy in a phase 3 trial of 300 neoadjuvant patients.

I-SPY2 is a multicenter, phase 2 trial using response-adaptive randomization within molecular subtypes defined by receptor status and MammaPrint risk to evaluate novel agents as neoadjuvant therapy for breast cancer. I-SPY 2 evaluates drugs (or combination of drugs) in parallel with the goal of determining which drugs work best in various types of breast cancer. I-SPY 2 patients are given chemotherapy before surgery so that response to treatment can be assessed. The primary endpoint of the study is pathologic complete response (pCR). Patients who participated in this study had tumors ≥ 2.5 cm, were HER2-negative, and if the cancer was hormone receptor positive (HR+) had to be classified as MammaPrint high risk status. Lead investigator of the study arm, Dr. Lajos Pusztai, Professor of Medicine and Director of Breast Cancer Translational Research at Yale Cancer Center, presented the efficacy and biomarker results which showed the predicted probability of pCR for the overall HER2-negative group, (22% vs 37%) and by subtypes, in HER2-negative/ER-positive (14% vs 28%) and triple negative (TNBC) (27% vs 47%) breast cancer subtypes.

The investigators also evaluated proposed potential markers that could identify the subgroup of patients who selectively benefited from the inclusion of immune enhancing agents such as durvalumab and DNA damage response targeting agents such as olaparib. Among the HR+/HER2- cohort, the MammaPrint ultra-high group was the primary beneficiary of the combined therapy (pCR rates 64% with the combination versus 22% with chemotherapy alone). Specific gene expression signatures thought to be associated with response were prospectively identified and the following were found to be associated with higher pCR in the experimental arm among TNBC: low CD3/CD8 ratio; high Macrophage/T cell-MHC class II ratio, and high proliferation. The safety signals were not unexpected. Adverse events were consistent with known side effects of these drugs. Overall 11% of patients in durvalumab + olaparib arm experienced immune-related grade 3 adverse events vs 1.3% in the control arm. According to Dr. Pusztai, chaperone for this arm in the I-SPY 2 TRIAL, "These results provide further evidence for the clinical value of immunotherapy in early stage breast cancer and suggest new avenues for how to exploit these drugs in HR+ breast cancers."

As noted by I-SPY 2 principal investigator, Dr. Laura Esserman of the University of California San Francisco, "There is a consistent signal of improved response from immuno-oncology and DNA damage response targeted agents in the adaptive I-SPY 2 platform trial as well as other trials, which gives us confidence that these types of agents will have a place in improving outcomes for women with highest risk early breast cancer. "

AACR has selected these findings as newsworthy and will be highlight during an AACR (Free AACR Whitepaper) webcast with the meeting program chair Dr. Antoni Ribas and AACR (Free AACR Whitepaper) President Dr. Elaine Mardis.

GRAIL to Present New Data at the American Association for Cancer Research (AACR) Annual Meeting

On April 27, 2020 GRAIL, Inc., a healthcare company whose mission is to detect cancer early, reported that new data for its investigational multi-cancer early detection blood test will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting I (Press release, Grail, APR 27, 2020, View Source [SID1234556604]). These new data evaluate the performance of GRAIL’s test in symptomatic participants with suspicion of cancer.

Today, the majority of deadly cancers do not have guideline-recommended screening tests available, and as a result, most cancers are detected too late, after they have progressed to late stages when chances of survival are much lower. There is also a high unmet need for early detection in the diagnostic assessment of symptomatic patients who are being evaluated for cancer. GRAIL’s multi-cancer early detection technology can detect more than 50 cancers, with a very low false positive rate of less than one percent, through a single blood draw. When a cancer signal is detected, the test can also identify where the cancer is located in the body (the tissue of origin) with high accuracy. This technology could be particularly useful in directing a more efficient diagnostic workup in symptomatic patients who are being evaluated for cancer.

"We continue to make significant progress in the validation of our multi-cancer early detection blood test, and wanted to assess its potential to drive efficiencies in the diagnostic workup of patients who are showing symptoms," said Alex Aravanis, MD, PhD, Chief Scientific Officer and Head of R&D, and a co-founder of GRAIL. "These findings show that when our multi-cancer test detected a cancer signal, it also identified where in the body that cancer was located with high accuracy. This is critical information for healthcare providers, and demonstrates the feasibility of our test to potentially accelerate diagnosis in individuals with high suspicion of cancer by helping direct the diagnostic workup."

These new data represent a pre-specified sub-group from GRAIL’s foundational Circulating Cell-free Genome Atlas (CCGA) study, which included more than 15,000 participants with or without a diagnosis of cancer. In the sub-group analysis reported at AACR (Free AACR Whitepaper), participants being evaluated for suspicion of cancer were classified as clinically confirmed cancer (n=164 in training, n=75 in validation) or clinically confirmed non-cancer (n=49 in training, n=15 in validation). In the confirmed non-cancer group, all training and validation samples were correctly predicted as non-cancer, or 100% specificity.

In the validation set, detection across all stages in the confirmed cancer group was 46.7% (n=35/75; 95% confidence interval [CI]: 35.1-58.6%) at 100% specificity. When renal cancers — which were overrepresented and subject to poor detection at early stages due to low tumor cfDNA fraction — were not included, detection across stages was 59.3% (n=35/59; 95% CI: 45.7-71.9%). In stages II and above, detection was 78.9% (n=30/38; 95% CI: 62.7-90.4%), all at 100% specificity. Performance was consistent across training and validation sets.

For cancers where a signal was detected, the tissue of origin (TOO) was predicted in 93.9% (n=62/66) of samples in training, and 100% (n=35/35) in validation. Of those with a TOO result, accuracy was 85.5% (n=53/62; 95% CI: 74.2-93.1%) and 97.1% (n=34/35; 95% CI: 85.1-99.9%), respectively.

The data are being presented online by David D. Thiel, MD, Chair, Mayo Clinic Florida Department of Urology. The presentation slides will be available at View Source after the presentation.

AACR Presentation Details

Abstract CT291
Lincoln Nadauld, et al. The PATHFINDER Study: Assessment of the implementation of an investigational multi-cancer early detection test into clinical practice
Session VPO.CT07.03 – Phase III Trials in Progress: April 27, 2020: 9:00AM-6:00PM EDT

Abstract CT021
David D. Thiel, et al. Prediction of cancer and tissue of origin in individuals with suspicion of cancer using a cell-free DNA multi-cancer early detection test
Session VCTPL02 – Early Detection and ctDNA: April 28, 2020: 1:40PM-1:50PM EDT

About CCGA

The Circulating Cell-free Genome Atlas (CCGA) study is a prospectively designed, observational, longitudinal, case-control study that has completed enrollment of approximately 15,000 participants with and without cancer across 142 sites in the United States and Canada. CCGA is designed to characterize the landscape of genomic cancer signals in the blood, and to discover, train, and validate GRAIL’s multi-cancer early detection blood test through three pre-planned sub-studies. To learn more about CCGA, please visit www.grail.com.

About GRAIL’s Multi-Cancer Early Detection Test

GRAIL’s multi-cancer early detection test is designed to detect cancers in early stages, when the chance of survival is higher than if cancer is detected after symptoms appear. Clinical data have shown the ability of this technology to detect more than 50 cancer types with a very low false positive rate of less than one percent. GRAIL’s test was designed to minimize false positives in order to limit associated harms, including patient anxiety and unnecessary diagnostic workups. When a cancer signal is detected, the test has been able to identify where in the body the cancer is located with high accuracy, an important step to guiding diagnostic next steps and care.

GRAIL’s methylation-based technology preferentially targets the most informative regions of the genome and is designed to use its proprietary database and machine-learning algorithms to both detect the presence of cancer and identify the tumor’s tissue of origin. GRAIL believes its sequencing database of cancer and non-cancer methylation signatures is the largest of its kind.