On May 29, 2020, Blueprint Medicines Corporation Presented the Corporate Presentation (Press release, Blueprint Medicines, MAY 29, 2020, View Source [SID1234558775]).

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On May 29, 2019 Sihuan Pharmaceutical Holdings Group Ltd. (HKEx: 0460), the largest cardio-cerebral vascular ("CCV") drug manufacturer in China’s prescription drug market, reported the third generation of EGFR inhibitor XZP-5809, a Category 1 innovative drug developed by the Group, has been granted drug clinical trial approval by the National Medical Products Administration of the PRC (Press release, Sihuan Pharmaceutical, MAY 29, 2019, View Source [SID1234570979]).. The New Drug is a Category 1 innovative drug of the PRC developed by the Group .

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The New Drug is a novel third-generation epithelial growth factor receptor-tyrosine kinase inhibitor (”EGFR-TKI”) that has strong targeting capability, and can be taken orally. It features innovative structure, established mechanism and irreversible binding to EGFR. The New Drug has better selection with higher activity against gene-mutation EGFR and lower activity against wild-type EGFR.

Compared with products of the same type, the New Drug has distinct advantages in its activity and safety, based on the data collected from the completed preclinical trial. The New Drug and its metabolite have demonstrated lower activity against wild-type EGFR. With its better safety profile and global competitive advantage, the New Drug will be considered as a new treatment option for cancer patients.

Dr. Che Fengsheng, Chairman and CEO of Sihuan Pharmaceutical, said, "Significant progress has been made in the field of lung cancer treatment, including anti-cancer immunotherapy, but targeted therapy is still considered the best choice for non-small cell lung cancer (‘NSCLC’) with EGFR mutation."

The preclinical pharmacodynamic data and toxicological data indicate that the New Drug has the following characteristics: good efficacy against EGFR sensitive mutations (exon 19 deletion and L858R mutation) and against acquired resistance mutations (T790M mutation); potential clinical efficacy for patients with lung cancer brain metastasis; better safety profile and less impact on cardiac function when compared with drugs of the same type on the market. The clinical indication for the New Drug candidate is potential to be solid tumors such as locally advanced or metastatic lung cancer with EGFR-sensitive mutations (exon 19 deletion and L858R mutation) and acquired resistance mutations (T790M mutation).

Dr. Che stated, "The Group is committed to the fundamental research of innovative drugs, and finally obtains the clinical trial approval of the New Drug by overcoming the technical difficulties encountered. The obtained clinical trial approval for the New Drug will further enrich the Group’s product line layout in innovative drugs. In addition to the New Drug, the Group currently has Janagliflozin, an innovative drug in the field of anti-diabetes and a number of small molecule targeted innovative drugs such as Birociclib in the field of anti-tumor are in clinical trials and are making progress well. The layout of innovative drugs in various therapeutic fields has established a solid foundation for the Group’s research and development platform of innovative drugs."

Lung cancer is one of the malignant tumors with the highest morbidity and mortality in the world. In 2018, the number of cases of lung cancer around the world was 2.093 million. According to the cancer report statistics of the PRC, in terms of the number of cases, lung cancer ranks the first in the incidence of malignant tumors with approximately 781 thousand as the annual incidence cases number. According to the World Health Organization’s forecast, the number of lung cancer deaths in the PRC will exceed 1 million each year by 2025.

On May 29, 2020 Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") reported that the Japan Ministry of Health, Labour and Welfare (MHLW) has approved XTANDI (enzalutamide), an oral androgen receptor signaling inhibitor, for the treatment of prostate cancer patients with distant metastasis. With this approval, XTANDI is now indicated for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC), a form of prostate cancer that has spread to other parts of the body and still responds to a medical or surgical treatment that lowers testosterone (Press release, Astellas, MAY 29, 2020, View Source [SID1234558658]).1,2 This is in addition to an existing indication for castration-resistant prostate cancer (CRPC).

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The approval for mHSPC is based on results from the ARCHES triali, a randomized multi-national Phase 3 study which evaluated enzalutamide plus androgen deprivation therapy (ADT) versus placebo plus ADT in 1,150 men with mHSPC and met its primary endpoint of radiographic progression-free survival (rPFS).3 It is also supported by data from the ENZAMET trialii, an overseas Phase 3 study evaluating enzalutamide plus ADT versus ADT plus a standard nonsteroidal antiandrogen therapy (bicalutamide, nilutamide or flutamide) in men with mHSPC.4

"Enzalutamide with androgen deprivation therapy led to a significant delay in the risk of progression of metastatic disease or death, and this delay was associated with maintained quality of life and a reduced need for subsequent therapies over time. These endpoints are all critically important to men with metastatic prostate cancer," said Andrew Armstrong, M.D., Professor of Medicine, Surgery, Pharmacology and Cancer Biology, Director of Research in the Duke Cancer Institute’s Center for Prostate and Urologic Cancers and lead investigator of the ARCHES trial. "The research supporting the approval provides compelling evidence to consider enzalutamide as a treatment option for men with mHSPC."

Data from the ARCHES trial showed enzalutamide plus ADT significantly reduced the risk of radiographic progression or death by 61% versus placebo plus ADT in men with mHSPC.5 The ENZAMET trial demonstrated a 33% reduction in the risk of death in men with mHSPC receiving enzalutamide plus ADT compared to those who took a nonsteroidal antiandrogen therapy plus ADT.6

The safety analyses of the ARCHES and ENZAMET trials were generally consistent with the safety profile of enzalutamide in previous clinical trials in CRPC. In the ARCHES trial, adverse drug reactions were reported in 53.0% of patients. Major adverse drug reactions with an incidence of more than 10% were hot flush (20.5%) and fatigue (14.9%). In the ENZAMET trial, serious adverse drug reactions were reported in 3.0% of patients. Serious adverse drug reactions observed in 2 or more patients were seizure (0.9%), hypertension (0.5%) and fatigue (0.4%).

"Today’s MHLW approval of XTANDI marks continued progress to provide a treatment option to men earlier in their advanced prostate cancer treatment journey," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Global Therapeutic Area Head, Oncology Development. "At Astellas, we have made a commitment to fight cancer and continue to build a robust oncology portfolio to help meet the needs of patients."

About metastatic Hormone-Sensitive Prostate Cancer (mHSPC)
In men with prostate cancer, the disease is considered metastatic once the cancer has spread outside of the prostate gland to other parts of the body. Men are considered hormone- (or castration-) sensitive if their disease still responds to medical or surgical treatment that lowers testosterone.

About the ARCHES trial
The company-sponsored, Phase 3, randomized, multinational, double-blind, placebo-controlled, ARCHES trial (NCT02677896) enrolled 1,150 patients with mHSPC at sites in the U.S., Canada, Europe, South America, and the Asia-Pacific region. Patients in the trial were randomized to receive enzalutamide 160 mg daily or placebo and continued on a luteinizing hormone-releasing hormone (LHRH) agonist or antagonist or had a history of bilateral orchiectomy. The primary endpoint of the trial was radiographic progression-free survival (rPFS) assessed by blinded independent central review. rPFS was defined as the time from randomization to radiographic disease progression at any time or death within 24 weeks after study drug discontinuation. Patients were stratified by volume of disease (low vs high) and prior docetaxel therapy for prostate cancer (no prior docetaxel, 1-5 cycles, or 6 prior cycles).3

About the ENZAMET trial
ENZAMET is an overseas Phase 3 study funded by Astellas and sponsored by the University of Sydney with trial sites in Australia, Canada, Ireland, New Zealand, UK and U.S. The trial evaluated the potential of enzalutamide plus androgen deprivation therapy (ADT) versus a conventional non-steroidal anti androgen (NSAA) plus ADT in 1,125 men with mHSPC. The primary endpoint for the trial is overall survival (OS; 3-years). Additional details about ENZAMET (NCT02446405) are available on www.clinicaltrials.gov.4

About XTANDI (enzalutamide)
Enzalutamide is an androgen receptor signaling inhibitor indicated for the treatment of patients with castration-resistant prostate cancer (CRPC) and metastatic hormone-sensitive prostate cancer (mHSPC).

Important Safety Information
For important Safety Information for enzalutamide please see the Package Insert.

On May 29, 2020 AstraZeneca and Daiichi Sankyo Company, Limited (Daiichi Sankyo) reported that Results from the Phase II DESTINY-CRC01 trial of s Enhertu (trastuzumab deruxtecan) demonstrated clinically meaningful activity in patients with HER2-positive unresectable and/or metastatic colorectal cancer who received at least two prior lines of standard treatment (Press release, AstraZeneca, MAY 29, 2020, View Source [SID1234558675]).

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Colorectal cancer is the third most common cancer and second most common cause of cancer death globally.1 There are currently no medicines approved to specifically treat HER2-positive colorectal cancer, which affects approximately 2-5% of patients with colorectal cancer.2

The primary endpoint of confirmed objective response rate (ORR), assessed by independent central review, showed 45.3% of patients with HER2-positive (defined as IHC3+ or IHC2+/ISH+) advanced colorectal cancer treated with Enhertu monotherapy (6.4mg/kg) achieved a tumour response. A disease control rate (DCR) of 83.0% was observed with a median progression-free survival (PFS) of 6.9 months. Median duration of response (DoR) and overall survival (OS) had not yet been reached at the time of data cut-off.

Salvatore Siena, MD, Professor of Medical Oncology, Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, and Niguarda Cancer Center, Milan, Italy and principal investigator of the DESTINY-CRC01 trial, said: "Understanding new ways we can treat patients with colorectal cancer, such as targeting HER2, is critical as patients have few remaining treatment options once progression occurs in the advanced disease setting. The results from DESTINY-CRC01 in patients with HER2-positive advanced colorectal cancer are striking and warrant further research, especially considering many of these patients have had numerous prior therapies."

José Baselga, Executive Vice President, Oncology R&D, said: "These clinically meaningful and durable responses in patients with advanced HER2-positive colorectal cancer support our belief that HER2 is an important treatment target in this disease. Enhertu has now demonstrated impressive clinical activity in four different cancer settings, reinforcing the potential of this remarkable medicine to transform patient outcomes across a range of HER2-targetable tumours."

Antoine Yver, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo, said: "Metastatic colorectal cancer has a devastating prognosis and there have been limited treatment advances following progression on 1st-line treatment and there are no therapies approved that specifically target HER2. We are encouraged by the tumour response rates seen in patients with previously treated advanced colorectal cancer and we will continue to explore the potential of Enhertu to address this unmet medical need."

Summary of results

CI, confidence interval; CR, complete response; PR, partial response; SD, stable disease; NE, not estimable
i. Enhertu 6.4 mg/kg.
ii. Primary cohort included patients with HER2-positive disease (defined as IHC3+ or IHC2+/ISH+).
iii. As assessed by independent central review.
iv. ORR is (CR + PR).
v. DCR is (CR + PR + SD).

Two exploratory cohorts enrolled patients with tumours with lower levels of HER2 expression (IHC2+/ISH- and IHC1+, respectively). There were no responses seen in these exploratory cohorts.

Prespecified exploratory analysis evaluated ORR in subgroups including patients previously treated with a prior anti-HER2 regimen (n=16). In these patients an ORR of 43.8% (95% CI, 19.8-70.1) was seen. Patients were treated with a median of four prior lines of therapy (2-11), with all patients having received prior chemotherapy treatment with irinotecan and oxaliplatin. The median treatment duration was 4.8 months (1-11). As of data cut-off on 9 August 2019, 38.5% (30 out of 78) remained on treatment across cohorts.

The overall safety and tolerability profile of Enhertu in DESTINY-CRC01 was consistent with that seen in previously reported Enhertu trials. The most common Grade 3 or higher treatment-emergent adverse events were decreased neutrophil count (25.6%) and anaemia (14.1%). There were five cases (6.4%) of interstitial lung disease (ILD) and pneumonitis determined by an independent adjudication committee. Two were Grade 2 and one was Grade 3. Two deaths (Grade 5) were determined to be due to ILD.

Results from DESTINY-CRC01 were presented during the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program on 29 to 31 May 2020.

Colorectal cancer

Colorectal cancer is the third most common cancer and second most common cause of cancer death globally.1

Approximately 25% of patients have metastatic disease at diagnosis, meaning the disease has spread to distant organs, and about 50% of patients with colorectal cancer will eventually develop metastases.3 Overexpression and amplification of HER2, a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours including breast, gastric, lung and colorectal cancers, occurs in approximately 2-5% of all patients with colorectal cancer.2,4 Research indicates that HER2 amplification may be associated with resistance to anti-epidermal growth factor receptor (EGFR)-targeted therapy and shorter survival.4,5

DESTINY-CRC01

DESTINY-CRC01 is a global, Phase II, open-label, multi-centre trial testing the safety and efficacy of Enhertu in patients (n=78) with HER2-expressing, unresectable and/or metastatic colorectal cancer. DESTINY-CRC01 excluded patients with a mutation in the RAS or BRAF gene. The primary cohort of the trial enrolled patients (n=53) with HER2-positive disease (defined as IHC3+ or IHC2+/ISH+). The primary endpoint of the trial is confirmed ORR by independent central review in the primary cohort. ORR, or tumour response rate, represents the percentage of patients whose disease decreased and/or disappears. Secondary endpoints include DCR, DoR, PFS and OS. Two additional exploratory cohorts enrolled patients whose tumours had lower levels of HER2 expression [HER2 IHC2+/ISH- (n=7) and HER2 IHC1+ (n=18), respectively].6

Enhertu

Enhertu (trastuzumab deruxtecan, fam-trastuzumab deruxtecan-nxki in the US) is a HER2-directed antibody drug conjugate (ADC) and is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ("payload") to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells.

Enhertu (5.4mg/kg) is approved in the US and Japan for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens based on the DESTINY-Breast01 trial.

Enhertu clinical development

A comprehensive development programme is underway globally with six registrational trials evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable cancers including breast, gastric and lung cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

In May 2020, Enhertu received Breakthrough Therapy Designation (BTD) from the US FDA for the treatment of patients with HER2-positive unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma who have received two or more prior regimens including trastuzumab and Orphan Drug Designation for patients with gastric cancer, including gastroesophageal junction cancer. In March 2018, Enhertu received a SAKIGAKE designation for potential use in the same HER2-positive gastric cancer patient population and a supplemental New Drug Application was recently submitted to the Japan Ministry of Health, Labour and Welfare.

In May 2020, Enhertu also received a BTD for the treatment of patients with metastatic non-small cell lung cancer whose tumours have a HER2 mutation and with disease progression on or after platinum-based therapy.

Collaboration between AstraZeneca and Daiichi Sankyo

In March 2019, AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialise Enhertu worldwide, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is solely responsible for manufacturing and supply.

AstraZeneca in oncology

AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With six new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to AstraZeneca’s main capabilities, the Company is actively pursuing innovative partnerships and investment that accelerate the delivery of our strategy, as illustrated by the investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and ADCs – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and, one day, eliminate cancer as a cause of death.

On May 29, 2020 Bio-Path Holdings, Inc., (NASDAQ: BPTH), a biotechnology company leveraging its proprietary DNAbilize antisense RNAi nanoparticle technology to develop a portfolio of targeted nucleic acid cancer drugs, reported the presentation of a poster highlighting the clinical trial design of its Phase 2 study of BP1001 (prexigebersen) at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place virtually from May 29-31, 2020 (Press release, Bio-Path Holdings, MAY 29, 2020, View Source [SID1234558691]).

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The poster, titled, "A Phase II Study of BP1001 (liposomal Grb2 antisense oligonucleotide) in Patients with Hematologic Malignancies," was presented virtually by Dr. Maro Ohanian, Department of Leukemia, University of Texas M.D. Anderson Cancer Center. The poster describes the Phase 2 study design of BP1001 (liposomal Grb2 antisense), the Company’s lead drug candidate, in combination with decitabine as a potential treatment for patients diagnosed with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS).

"This innovative trial design for BP1001 is unique in that it allowed us to adjust our treatment to include newly approved therapies that we believed would be enhanced from combination with our DNAbilize technology. We believe this robust design will provide for the best outcomes for patients and will be the most expeditious route to bringing BP1001 to market. We are delighted to have the design presented and expect that it will enhance visibility for our DNAbilize platform and its versatility among an audience dedicated to bringing new cancer treatments to patients," stated Peter Nielsen, President and Chief Executive Officer of Bio-Path Holdings.

The Phase 2 clinical trial is a multi-center, open label study with two parallel cohorts of BP1001 in combination with decitabine in untreated AML and high risk MDS patients or refractory/relapsed AML and high risk MDS patients who are ineligible or unwilling to receive intensive induction therapy. The primary objective of the study is to assess whether BP1001 in combination with decitabine provides higher response rates than decitabine alone in AML or high risk MDS patients. In addition, a six-patient safety run-in of BP1001 and decitabine was completed with no dose adjustment required.

BP1001 is a neutral liposome incorporated with nuclease-resistant, hydrophobic P-ethoxy antisense oligodeoxynucleotides targeted to Grb2 mRNA. Grb2 is an adaptor protein that links oncogenic tyrosine kinases with downstream kinases, such as ERK and AKT, which are critical to cell proliferation and survival. Preclinical results showed that BP1001 enhanced the inhibitory effects of cytarabine or decitabine against AML cells.

The poster also describes future development plans for BP1001 in AML. Preclinical results suggest that BP1001 plus venetoclax plus decitabine triple combination could be more efficacious than the BP1001 + decitabine combination against AML cells. Venetoclax will be added to the study, thus exploring three-drug combinations of BP1001, venetoclax and decitabine. There will be three patient cohorts in the study:

•Untreated AML patients will be treated with BP1001 plus venetoclax plus decitabine.
•Refractory/relapsed AML patients will be treated with BP1001 plus venetoclax plus decitabine.
•A third cohort of BP1001 + decitabine will be offered to refractory/relapsed AML patients who are venetoclax resistant or intolerant, or not considered by the investigator as optimal candidates for venetoclax-based therapy.