On December 10, 2018 AstraZeneca reported a new collaboration with Cancer Research UK to launch a centre of excellence in genetic screening, cancer modelling and big data processing aimed at accelerating the discovery of new cancer medicines (Press release, AstraZeneca, DEC 10, 2018, View Source [SID1234531979]). The Functional Genomics Centre will further develop CRISPR technology to better understand the biology of cancer, creating biological models that may be more reflective of human disease, and advancing computational approaches to better analyse big datasets. These approaches are designed to inform new druggable targets in oncology by using clinical insights to better understand tumour disease and resistance mechanisms.

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Functional genomics aims to understand the complex relationship between genetic changes happening within DNA and how these translate to cellular changes in disease. Knowing the functional genomic drivers of disease enables scientists to more accurately select the right drug targets and increases the probability of success in the clinic.

Mene Pangalos, Executive Vice President, Innovative Medicines & Early Development, AstraZeneca, said: "The best science doesn’t happen in isolation which is why AstraZeneca is committed to advancing innovative science through collaboration. This new centre of excellence with Cancer Research UK will combine our expertise in functional genomics and CRISPR technology to identify new biological pathways driving disease and will accelerate the development of new cancer medicines for patients."

Dr Iain Foulkes, Cancer Research UK’s Executive Director of Research and Innovation, said: "We’re delighted to collaborate with AstraZeneca on this exciting new initiative which will give leading Cancer Research UK scientists and our alliance partners access to the latest in CRISPR technology. As we move into an era of personalised medicine, we’ve reached a turning point in our ability to harness powerful technologies in the pursuit of targeted cancer therapies. We hope that this will translate into urgently needed new therapies for patients with hard to treat cancers such as lung, pancreatic, oesophageal and brain tumours."

The Functional Genomics Centre will be located at the Milner Therapeutics Institute at the University of Cambridge. AstraZeneca and Cancer Research UK will have independent use of the Centre’s facilities, and their scientists will work alongside each other to facilitate collaboration, technical innovation and scientific progress.

At the Centre, scientists will have access to the next generation of CRISPR libraries for silencing or activating every gene in the genome, accessed through an extension of the existing collaboration between AstraZeneca and the Wellcome Sanger Institute. This collaboration includes access to the Wellcome Sanger Institute’s most recent versions of human and mouse genome-wide CRISPR/Cas9 knockout libraries, as well as Cas9 and dual gRNA expression vectors. This extends the application of CRISPR technology with vectors, providing enhanced sensitivity and specificity in gene editing, leading to easier targeting and identification.

A separate collaboration between AstraZeneca and the California-based Innovative Genomics Institute (IGI) will aim to use CRISPR to uncover genes and disease pathway mechanisms involved in DNA Damage Response (DDR), a key process involved in many cancers and one of AstraZeneca’s four key platforms in oncology. Research will focus on identifying potential therapeutic strategies for DDR inhibitors, including combinations, in oncology.

On December 10, 2018 Achilles Therapeutics ("Achilles" or "the Company"), a biopharmaceutical company using neoantigens to develop personalised cancer immunotherapies, reported that it has appointed Dr Edwin Moses as Chairman of its Board of Directors (Press release, Achilles Therapeutics, DEC 10, 2018, View Source [SID1234531978]). In addition, Dr Iraj Ali, currently Interim CEO, will become the permanent, full-time CEO of the Company.

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Dr Moses was most recently CEO of Ablynx NV which was acquired by Sanofi for $4.8Bn in 2018. Edwin was CEO at Ablynx for more than 12 years and built it from a small R&D-focused organisation into a five hundred person commercial-ready business with a broad biologics pipeline including a wholly-owned product for a rare hematologic indication which was approved for use in Europe earlier this year. At Ablynx, Edwin led the Euronext Brussels listing, multiple successful private and public financings and the NASDAQ listing in 2017. He was also responsible for delivering a series of multi-billion-pound collaborations with major pharmaceutical companies.

Edwin has more than 25 years of Board level experience, both as CEO and Chairman, in more than 10 European life science companies. During his career to date, Edwin has raised more than €500M in equity and debt financing.

Dr Ali joined Achilles in January 2018 as Interim CEO, whilst also serving as a Partner of Syncona Ltd, Achilles’ founding investor. He joined Syncona in 2012 and was an investment partner and Board member of Nightstar Therapeutics, Blue Earth Diagnostics and Achilles Therapeutics. Dr Ali was previously with McKinsey & Company where he was involved in several major pharmaceutical launches across developed and emerging markets and was a co-founder of McKinsey’s US launch practice and leader of speciality launches in Europe.

Edwin Moses, Chairman of Achilles, said:

"I am delighted to become the Chairman of Achilles. The Company was founded by world-leading experts in the understanding of cancer evolution, bioinformatics and the development of cell-based immunotherapies. The potential of the technology is extremely exciting and together with a dynamic and talented management team and Board, I am very much looking forward to building an international immunotherapeutic company and realizing the full potential of the core science to develop products to improve the lives of patients and create value for investors."

Iraj Ali, CEO of Achilles, added:

"We are on the brink of a revolution in cancer therapy driven by the convergence of bioinformatics and immuno-oncology, both of which are developing at a staggering pace. I have been involved with the development of the Achilles concept from its inception and I am delighted to become the CEO on a permanent basis and to welcome someone of Edwin’s calibre to be Chairman of our Board. Edwin brings exceptionally relevant experience to Achilles and together with his stewardship, I look forward to leading this business through its next phase of growth."

Dr Martin Murphy, Chief Executive Officer of Syncona Investment Management Ltd commented:

"Iraj has played an integral role in the development of Syncona and has played an instrumental part in the foundation and subsequent progress of Achilles. We are delighted that he has chosen to transition from being the interim CEO to take on the role on a full-time basis. It serves to underscore our shared belief in Achilles, which is a truly innovative healthcare business with an opportunity to grow into a globally competitive commercial company."

Achilles also recently announced the appointment of industry leader Michael F. Giordano, M.D., previously the Head of Immuno-Oncology and Oncology Development at Bristol-Myers Squibb responsible for approvals of Yervoy and Opdivo, as a non-executive director to its Board.

The Achilles Board composition is now as follows:

Edwin Moses, Chairman

Iraj Ali, Chief Executive Officer

Martin Murphy, Non-Executive Director

Elisa Petris, Observer

Professor Karl Peggs, Founder Director

Ian Walker, Non-Executive Director

Michael F. Giordano, Non-Executive Director

– Ends –

Further information:

Achilles Therapeutics

Dr Iraj Ali – Chief Executive Officer

+44 (0)1438 906 906

[email protected]

JW Communications

Julia Wilson

+44 (0)7818 430877

[email protected]

Consilium Strategic Communications

Mary-Jane Elliott, Sukaina Virji, Melissa Gardiner

Tel: +44 (0) 203 709 5000

Email: [email protected]

On December 8, 2018 Novartis reported data from subgroup analyses of the three pivotal Phase III MONALEESA trials showing that Kisqali (ribociclib) plus endocrine therapy extended progression-free survival (PFS) compared to endocrine therapy alone, regardless of the presence of visceral metastases in pre-, peri- and postmenopausal women with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced breast cancer1 (Press release, Novartis, DEC 8, 2018, View Source;advanced-breast-cancer-in-patients-with-difficult-to-treat-visceral-disease-300761974.html [SID1234531976]). These data will be presented today at the San Antonio Breast Cancer Symposium (SABCS) (Abstract #P6-18-07).

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"Nearly 60% of patients enrolled in the MONALEESA clinical trials had visceral metastases, and all benefited from treatment with ribociclib in combination with endocrine therapy," said Denise Yardley, MD, Principal Investigator, Sarah Cannon Research Institute. "These results, coupled with the NCCN and ABC4 recommended treatment guidelines for HR+ advanced breast cancer patients with visceral metastases, support the use of ribociclib combination therapy as a standard of care in this patient population."

In patients with visceral metastases, Kisqali plus endocrine therapy extended median PFS by 11.5 months in MONALEESA-2 (24.9 months vs 13.4 months) and 13.4 months in MONALEESA-7 (23.8 months vs 10.4 months) compared to endocrine therapy alone. Median PFS for patients with visceral metastases in the MONALEESA-3 trial still has not been reached compared to 16.5 months median PFS in patients receiving endocrine therapy alone1.

Kisqali plus endocrine therapy demonstrated consistent efficacy across the MONALEESA trials in patients with and without visceral metastases. In patients with visceral metastases and measurable disease, the overall response rate (ORR) in patients who received Kisqali plus endocrine therapy compared to endocrine therapy alone was 53% vs 40% (MONALEESA-2), 50% vs 38% (MONALEESA-7) and 48% vs 31% (MONALEESA-3). Patients without visceral disease showed an ORR of 59% vs 35%, 52% vs 32% and 49% vs 39% in the respective MONALEEA-2, MONALEESA-7 and MONALEESA-3 trials1.

"Patients living with HR+/HER2- advanced breast cancer who have visceral metastases often have a poorer prognosis and are at higher risk for treatment resistance and disease progression than those without," said Samit Hirawat, MD, Head, Novartis Oncology Global Drug Development. "These sub analyses reaffirm that it is critical to treat HR+ advanced breast cancer with a CDK4/6 combination therapy, such as Kisqali plus fulvestrant or an aromatase inhibitor, to give all patients, especially those with visceral metastases, the strongest option for delaying disease progression."

Adverse events for patients with visceral metastases were consistent with those observed in the overall study populations and generally manageable through dose interruptions or reductions1.

About Kisqali (ribociclib)
Kisqali (ribociclib) is the CDK4/6 inhibitor with the largest body of first-line clinical trial evidence demonstrating consistent, superior and sustained efficacy compared to endocrine therapy alone4.

Kisqali is a selective cyclin-dependent kinase inhibitor, a class of drugs that help slow the progression of cancer by inhibiting two proteins called cyclin-dependent kinase 4 and 6 (CDK4/6). These proteins, when over-activated, can enable cancer cells to grow and divide too quickly. Targeting CDK4/6 with enhanced precision may play a role in ensuring that cancer cells do not continue to replicate uncontrollably4.

Kisqali was initially approved by the US Food and Drug Administration (FDA) in March 2017 and by the European Commission in August 2017, as initial endocrine-based therapy for postmenopausal women with HR+/HER2- locally advanced or metastatic breast cancer in combination with an aromatase inhibitor based on findings from the pivotal MONALEESA-2 trial. In July 2018, Kisqali was approved by the FDA for the treatment of pre-, peri- or postmenopausal women in the US, and indicated for use in combination with fulvestrant as both first- or second-line therapy in postmenopausal women. In November 2018, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending an expanded indication for Kisqali based on the MONALEESA-3 and MONALEESA-7 data. Regulatory filings are underway with other health authorities worldwide4.

Kisqali is approved for use in more than 70 countries around the world, including the United States and European Union member states. Kisqali is not currently approved for use in combination with fulvestrant or in premenopausal women in Europe. Kisqali was developed by the Novartis Institutes for BioMedical Research (NIBR) under a research collaboration with Astex Pharmaceuticals4.

Novartis is continuing to reimagine cancer by investigating Kisqali in early breast cancer (EBC). The NATALEE study is a Phase III clinical trial of Kisqali with endocrine therapy in the adjuvant treatment of HR+/HER2- EBC being conducted in collaboration with Translational Research In Oncology (TRIO)4.

About Novartis in Advanced Breast Cancer
For more than 30 years, Novartis has been tackling breast cancer with superior science, great collaboration and a passion for transforming patient care. With one of the most diverse breast cancer pipelines and one of the largest numbers of breast cancer compounds in development, Novartis leads the industry in discovery of new therapies and combinations, especially in HR+ advanced breast cancer, the most common form of the disease.

Kisqali (ribociclib) Important US Safety Information
KISQALI (ribociclib) is a prescription medicine used in combination with an aromatase inhibitor as the first hormonal-based therapy to treat pre/peri- and postmenopausal women and in combination with fulvestrant as the first hormonal-based therapy or following disease progression on hormonal therapy in postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. It is not known if KISQALI is safe and effective in children. KISQALI can cause a heart problem known as QT prolongation. This condition can cause an abnormal heartbeat and may lead to death. KISQALI is not indicated for concomitant use with tamoxifen due to an increased risk of QT prolongation. Patients should tell their health care provider right away if they have a change in their heartbeat (a fast or irregular heartbeat), or if they feel dizzy or faint. KISQALI can cause serious liver problems. Patients should tell their health care provider right away if they get any of the following signs and symptoms of liver problems: yellowing of the skin or the whites of the eyes (jaundice), dark or brown (tea-colored) urine, feeling very tired, loss of appetite, pain on the upper right side of the stomach area (abdomen), and bleeding or bruising more easily than normal. Low white blood cell counts are very common when taking KISQALI and may result in infections that may be severe. Patients should tell their health care provider right away if they have signs and symptoms of low white blood cell counts or infections such as fever and chills. Before taking KISQALI, patients should tell their health care provider if they are pregnant, or plan to become pregnant as KISQALI can harm an unborn baby. Females who are able to become pregnant and who take KISQALI should use effective birth control during treatment and for at least 3 weeks after the last dose of KISQALI. Do not breastfeed during treatment with KISQALI and for at least 3 weeks after the last dose of KISQALI. Patients should tell their health care provider about all of the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements since they may interact with KISQALI. Patients should avoid grapefruit or grapefruit juice while taking KISQALI. The most common side effects (incidence ≥20%) include white blood cell count decreases, nausea, infections, tiredness, diarrhea, vomiting, hair loss, headache, constipation, rash, and cough. The most common Grade 3/4 side effects (incidence >5%) were low neutrophils, low leukocytes, abnormal liver function tests, and low lymphocytes. Abnormalities were observed in hematology and clinical chemistry laboratory tests.

On December 8, 2018 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that updated safety and efficacy data from the ongoing phase 1 study with [fam-] trastuzumab deruxtecan, an investigational HER2 targeting antibody drug conjugate (ADC), were presented for a subgroup of patients with heavily pretreated HER2 low expressing metastatic breast cancer during a Poster Session at the 2018 San Antonio Breast Cancer Symposium (SABCS) (#P6-17-02) (Press release, Daiichi Sankyo, DEC 8, 2018, https://www.prnewswire.com/news-releases/daiichi-sankyo-presents-updated-phase-1-results-of-fam–trastuzumab-deruxtecan-ds-8201-in-patients-with-her2-low-expressing-metastatic-breast-cancer-at-2018-san-antonio-breast-cancer-symposium-sabcs-300762111.html [SID1234531975]).

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The updated analysis of 43 evaluable patients with HER2 low expressing metastatic breast cancer (IHC 2+/ISH- or IHC 1+), who received [fam-] trastuzumab deruxtecan at a recommended expansion dose of 5.4 or 6.4 mg/kg, demonstrated a confirmed overall response rate of 44.2 percent (19/43 patients) and a disease control rate of 79.1 percent (34/43 patients). Preliminary estimate of median duration of response was 9.4 months (range: 1.5+, 23.6+), and median progression-free survival was 7.6 months (95 percent CI: 4.9, 13.7). A total of 54 patients with heavily pretreated (median 7.5 prior anticancer regimens) HER2 low breast cancer have received ≥1 dose [fam-] trastuzumab deruxtecan 5.4 or 6.4 mg/kg in the study and 23 patients remain on treatment as of data cut-off on October 12, 2018.

"While anti-HER2 therapies play an important role in the treatment of HER2 positive breast cancer, they historically have not demonstrated effectiveness against tumors that express lower levels of HER2," said Shanu Modi, MD, Breast Medical Oncologist, Memorial Sloan Kettering Cancer Center and study investigator. "These data offer preliminary evidence of [fam-] trastuzumab deruxtecan activity in HER2 low expressing breast cancers, and based on further study, we are beginning to consider the implications for how we classify and treat these patients."

A further subgroup analysis of 38 evaluable patients whose disease was also hormone receptor (HR) positive demonstrated a confirmed overall response rate of 47.4 percent (18/38 patients) and a disease control rate of 81.6 percent (31/38 patients) with [fam-] trastuzumab deruxtecan. Preliminary estimate of median duration of response was 11.0 months (range: 1.5+, 23.6+), and median progression-free survival was 7.9 months (95 percent CI: 4.4, 13.7) in this patient subgroup. A total of 45 patients with HR positive, HER2 low breast cancer have received ≥1 dose [fam-] trastuzumab deruxtecan 5.4 or 6.4 mg/kg in the study and 21 of these patients remain on treatment as of data cut-off.

"There are no anti-HER2 therapies currently approved for HER2 low expressing breast cancer, which represents about half of all breast cancers," said Gilles Gallant, BPharm, PhD, Vice President, DS-8201 Global Team Leader, Oncology Research and Development, Daiichi Sankyo. "Based on these data, plans for a phase 3 trial in patients with HER2 low metastatic breast cancer are underway, adding to our broad development program evaluating [fam-] trastuzumab deruxtecan in HER2 expressing breast cancers and other tumor types."

Updated overall safety data as of October 12, 2018 for all breast cancer patients in the ongoing phase 1 study were also reported at SABCS. Among 170 patients who received at least one dose of [fam-] trastuzumab deruxtecan 5.4 or 6.4 mg/kg for advanced breast cancer in the dose expansion or dose escalation part of the study (regardless of HER2 status), the most common adverse events (≥30 percent, any Grade) included nausea (79.4 percent), decreased appetite (54.1 percent), alopecia (46.5 percent), vomiting (45.9 percent), fatigue (42.4 percent), anemia (40.0 percent), constipation (38.2 percent) and diarrhea (38.2 percent). A total of 50.0 percent of the breast cancer patients experienced a Grade ≥3 adverse event and 22.9 percent had a serious adverse event, including 2.9 percent of patients who experienced an adverse event that lead to death.

ILD Data in Metastatic Breast Cancer Presented
An independent committee evaluates any reported cases of interstitial lung disease (ILD)/pneumonitis in the [fam-] trastuzumab deruxtecan clinical development program.The first analysis of ILD data, including adjudicated case results, in patients who received [fam-] trastuzumab deruxtecan for metastatic breast cancer across trials was presented at SABCS 2018 (Poster #P6-17-06).

Among 510 trial patients who received [fam-] trastuzumab deruxtecan for metastatic breast cancer at one of seven dose levels, there were fifty-four (54) investigator-reported ILD cases of any grade (10.6 percent) including four (4) Grade 5. Thirty-three (33) cases were adjudicated and twenty-eight (28) were considered to be drug-related ILD, including four (4) Grade 5 events.

Among 269 trial patients who received [fam-] trastuzumab deruxtecan for metastatic breast cancer at a 5.4 mg/kg dose, which is the recommended dose for continued development in HER2 positive breast cancer, there were fifteen (15) investigator-reported ILD cases any grade (5.6 percent) including one (1) Grade 5. Seven (7) cases were adjudicated and five (5) were considered to be drug-related ILD, including one (1) Grade 5 event.

A third data set was also presented for all patients with advanced solid tumors who received at least one dose of [fam-] trastuzumab deruxtecan across seven ongoing global studies. Among the 665 patients, there were sixty-six (66) investigator-reported ILD cases any grade (9.9 percent) including five (5) Grade 5. Thirty-eight (38) cases were adjudicated and thirty (30) were considered drug-related ILD, including four (4) Grade 5. Of the reported potential ILD cases from all studies, most were mild to moderate in severity, with 80.3 percent (53 of 66) ≤ Grade 2. The median time to onset of ILD was 149 (16–596) days. The study reflects all cases that occurred as of October 15, 2018.

Dose Justification in HER2 Positive Breast Cancer Presented
Research establishing 5.4 mg/kg as the recommended dose for continued development of [fam-] trastuzumab deruxtecan in advanced HER2 positive breast cancer was presented at SABCS (Poster #P6-17-10). A comprehensive analysis of observed data and exposure-response parameters from the phase 2 DESTINY-Breast01 trial in HER2 positive breast cancer and the ongoing phase 1 trial in multiple types of HER2 expressing tumors was conducted. Efficacy results for a total of 140 patients with HER2 positive breast cancer were included in the exposure-efficacy analysis, and safety results for a total of 276 patients with any tumor type were included in the exposure-safety analysis. Based on the benefit/risk profile, 5.4 mg/kg was chosen as the recommended dose for continued development in HER2 positive breast cancer for DESTINY-Breast01 and in phase 3 trials DESTINY-Breast02 and DESTINY-Breast03.

About HER2 Low Expressing Breast Cancer
Breast cancer is the most common cancer and the most common cause of cancer mortality among women worldwide.1 There were approximately 1.67 million new cases of breast cancer diagnosed in 2012.1

About one in five breast cancers (20 percent) are HER2 positive (IHC3+ or IHC2+/ISH+).2 HER2 is a tyrosine kinase receptor growth-promoting protein found on the surface of some cancer cells that is associated with aggressive disease and poorer prognosis.3,4 A number of HER2 targeting therapies are approved to treat HER2 positive metastatic breast cancer and have improved survival rates.5 The remaining 80 percent of breast cancers are classified as HER2 negative; however, about half still express some level of HER2 as a cell surface antigen.6 No anti-HER2 agents are indicated for these low expressing tumors, which may be defined as IHC 2+/ISH- or IHC 1+, and there is no targeted treatment paradigm for HER2 low expressing breast cancer.7 HER2 low expression has not been evaluated in clinical practice or in other clinical trials.

About the [Fam-] Trastuzumab Deruxtecan Phase 1 Study
An open-label, two-part phase 1 study is currently evaluating [fam-] trastuzumab deruxtecan in patients with advanced/unresectable or metastatic solid tumors that are refractory or intolerant to standard treatment, or for whom no standard treatment is available. The primary objective of the dose escalation part of this study was to assess the safety and tolerability of [fam-] trastuzumab deruxtecan and determine the maximum tolerated dose. Data from this part of the study were published in the Lancet Oncology.8

In the dose expansion part of the phase 1 study, [fam-] trastuzumab deruxtecan is given in one of two doses (5.4 mg/kg and 6.4 mg/kg) to patients with HER2 positive advanced or metastatic breast cancer and gastric cancer, HER2 low expressing breast cancer and other HER2 expressing solid tumors. Overall, 292 patients have been enrolled into this phase 1 study of [fam-] trastuzumab deruxtecan. For more information about the study, visit ClinicalTrials.gov.

About [Fam-] Trastuzumab Deruxtecan
[Fam-] trastuzumab deruxtecan (DS-8201; [fam-] trastuzumab deruxtecan in U.S. only; trastuzumab deruxtecan in other regions of world) is the lead product in the investigational ADC Franchise of the Daiichi Sankyo Cancer Enterprise. 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. Designed using Daiichi Sankyo’s proprietary ADC technology, [fam-] trastuzumab deruxtecan is comprised of a humanized HER2 antibody attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based linker. It is designed to target and deliver chemotherapy inside cancer cells and reduce systemic exposure to the cytotoxic payload (or chemotherapy) compared to the way chemotherapy is commonly delivered.

A broad and comprehensive development program with [fam-] trastuzumab deruxtecan is underway in North America, Europe and Asia. [Fam-] trastuzumab deruxtecan is in phase 3 development versus ado-trastuzumab emtansine (T-DM1) (DESTINY-Breast03) and versus investigator’s choice post T-DM1 (DESTINY-Breast02) for HER2 positive metastatic breast cancer; pivotal phase 2 clinical development for HER2 positive metastatic breast cancer resistant or refractory to T-DM1 (DESTINY-Breast01); pivotal phase 2 development for HER2 positive advanced gastric cancer resistant or refractory to trastuzumab (DESTINY-Gastric01); phase 2 development for HER2 expressing advanced colorectal cancer; phase 2 development for metastatic non-squamous HER2 overexpressing or HER2 mutated NSCLC; and, phase 1 development in combination with nivolumab for HER2 expressing metastatic breast and bladder cancer.

[Fam-] trastuzumab deruxtecan has been granted Breakthrough Therapy designation for the treatment of patients with HER2 positive, locally advanced or metastatic breast cancer who have been treated with trastuzumab and pertuzumab and have disease progression after T-DM1, and Fast Track designation for the treatment of HER2 positive unresectable and/or metastatic breast cancer in patients who have progressed after prior treatment with HER2 targeted therapies including T-DM1 by the U.S. Food and Drug Administration (FDA). [Fam-] trastuzumab deruxtecan has received SAKIGAKE Designation for the treatment of HER2 positive advanced gastric or gastroesophageal junction cancer by the Japan Ministry of Health, Labour and Welfare (MHLW).

[Fam-] trastuzumab deruxtecan is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.

On December 8, 2018 Generon BioMed Holding Ltd. (Generon), reported at the annual San Antonio Breast Cancer Symposium (SABCS), positive results from a placebo-controlled trial with F-627, a recombinant human Granulocyte Colony Stimulating Factor (rhG-CSF) protein, designed using Generon’s DikineTM technology platform (Press release, Generon (Shanghai), DEC 8, 2018, View Source [SID1234531974]).

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Led by Principle Investigator Dr. John Glaspy, Estelle, Abe and Marjorie Endowed Chair in Cancer Research at the Jonsson Comprehensive Cancer Center of UCLA, this global study of 122 woman with stage II-IV breast cancer receiving Myelotoxic chemotherapy demonstrates that subcutaneous administration of F-627 significantly reduced the duration of Grade 4 (severe) neutropenia in chemotherapy cycle 1 (P<0.0001); the mean treatment difference was 2.8 days (1.1 days vs. 3.9 days in the placebo arm). F-627 administration also resulted in lower incidence and shorter duration of Grade 4, Grade 3 and Grade 2 neutropenia. Other significant results included the finding that treatment with F-627 significantly reduced the incidence of febrile neutropenia (FN) (P<0.0016). The incidence of FN in the experimental arm was 4.8% and 28.2% in the placebo arm during cycle 1. Subjects in the experimental arm also had lower rates of antibiotic medication and pain medication use. In this study, F-627 was shown to be safe and well tolerated with no deaths, no injection site reactions and less gastrointestinal AEs (diarrhea, vomiting, stomatitis, and gastritis) than the placebo arm. During cycle 1 in the experimental arm, the five most common TEAEs (incidence rate >10%) were leukopenia, anemia, thrombocytopenia, nausea, and alopecia. Across all cycles, there were 17 SAEs from 15 subjects of which 15 were FN.

A single subcutaneous injection of F-627 significantly reduced the duration and incidence of severe neutropenia and febrile neutropenia while maintaining an excellent safety profile in patients with breast cancer undergoing high-dose chemotherapy.

Dr. Glaspy indicated that F-627 would provide an alternative treatment for patients with breast cancer and severe neutropenia secondary to myelotoxic chemotherapy. "The successful completion of this phase III trial exemplifies our continued commitment to developing innovative medicines on our various platforms that have the potential to treat patients with cancer" said Dr. William Daley, Generon’s Chief Medical Officer.

Dr. Daley also indicated that Yifan Pharmaceuticals, a controlling parent company of Generon, congratulated Generon’s team on the continued effort to develop innovative therapies. "This is yet another milestone and goal for Generon this year and is a significant step towards our mission of Innovating for Life. Generon is committed to bringing innovative oncology therapies to patients in China and the world" he commented.

About F-627

F-627, a rhG-CSF dimer, is a once-per-cycle therapy for the preventive management of neutropenia. Produced in Chinese Hamster Ovary (CHO) cells in serum-free cultures, F-627 leverages Generon’s proprietary Dimeric Cytokine (DiKineTM) technology platform to create an immunoglobulin-like dimeric structure, providing improved efficacy and a longer half-life. This product candidate is intended to treat cancer patients with neutropenia secondary to myelotoxic chemotherapy.