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Generon Presented Positive Phase III Results From a Double-Blind, Placebo Controlled-Clinical Trial of F-627 in Women with Breast Cancer Receiving Myelotoxic Chemotherapy

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.

Samsung Bioepis Announces Results of Additional One-Year Follow-Up Study Comparing Event-Free Survival of SB3 Trastuzumab Biosimilar Candidate to Reference Trastuzumab by ADCC Activity

On December 8, 2018 Samsung Bioepis Co., Ltd. reported the results of an additional one-year follow-up study comparing event-free survival (EFS) of SB3, a biosimilar candidate referencing HERCEPTIN 1 (trastuzumab), to reference trastuzumab (TRZ) by antibody-dependent cell-mediated cytotoxicity (ADCC) activity (Press release, Samsung Bioepis, DEC 8, 2018, View Source [SID1234531973]). ADCC is a key mechanism of action for trastuzumab. The study results are being presented at the 2018 San Antonio Breast Cancer Symposium (SABCS) which is being held December 4-8, 2018 in San Antonio, Texas.

For the study, patients with HER2 positive early or locally advanced breast cancer were randomly assigned to receive SB3 or TRZ concurrently with chemotherapy. Patients then underwent surgery followed by treatment with SB3 or TRZ. Following completion of such therapy, 367 patients participated in a long-term follow-up study, 186 of whom were treated with SB3 and 181 of whom were treated with TRZ. Within the group of 181 patients who received TRZ, 126 patients who were exposed to at least one kit from the TRZ lots with expiry dates between August 2018 and December 2019 during neoadjuvant period were considered "Exposed," while the remaining 55 patients were considered "Unexposed." Upon monitoring the quality attributes of TRZ for the development of SB3, a marked downward shift in ADCC activity was observed in some of the TRZ lots with expiry dates between August 2018 and December 2019.

Following 30.1 months of SB3 treatment and 30.2 months of TRZ treatment, there was no statistically significant difference in EFS between SB3 (96.7%) and the Unexposed arm (98.2%) (HR 1.19, 95% CI 0.23-6.18; p-value=0.8376). However, the results did show statistically significant difference in EFS between the Unexposed (98.2%) and Exposed (92.5%) arms within the TRZ treatment group (HR 0.07, 95% CI 0.01-0.58, p-value=0.0137). In addition, while there was no statistically significant difference in events between SB3 (4.8%) and the Unexposed (3.6%) arms, there was statistically significant difference in events within the TRZ treatment group between the Unexposed (3.6%) and Exposed (10.3%) arms. An event was defined as disease recurrence or progression, or death due to any cause. The study authors are currently looking into longer-term effects of SB3 and hope to publish these results at a later date.

"This study builds on the robust evidence for SB3, and demonstrates the trastuzumab biosimilar candidate’s comparable efficacy and safety profiles to the reference biologic over a longer time period," said Chul Kim, Senior Vice President and Head of Clinical Science, Samsung Bioepis. "We remain committed to advancing our strong pipeline of biosimilar candidates, so that more patients and healthcare systems may be able to benefit from biosimilar medicines."

The poster for this study will be exhibited at SABCS, as follows:

[P6-17-09] EVENT-FREE SURVIVAL BY ADCC STATUS FROM A FOLLOW-UP STUDY COMPARING SB3 (TRASTUZUMAB BIOSIMILAR) WITH REFERENCE TRASTUZUMAB FOR HER2 POSITIVE BREAST CANCER IN NEOADJUVANT SETTING [POSTER SESSION 6, December 8, 2018, 07:00AM – 09:00AM]

Novartis data demonstrates consistent efficacy and tolerability of Kisqali® combination therapy in HR+/HER2- advanced breast cancer in patients with difficult-to-treat visceral disease

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 cancer[1] (Press release, Novartis, DEC 8, 2018, View Source [SID1234531964]). These data will be presented today at the San Antonio Breast Cancer Symposium (SABCS) (Abstract #P6-18-07).

"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 alone.

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 trials[3].

"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 reductions.

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 alone[4].

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 uncontrollably[4].

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 worldwide[4].

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 Pharmaceuticals[4].

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].

Zymeworks Submits Investigational New Drug (IND) Application for ZW49 and Presents IND-Enabling Studies at the San Antonio Breast Cancer Symposium

On December 8, 2018 Zymeworks Inc. (NYSE/TSX: ZYME), a clinical-stage biopharmaceutical company developing multifunctional therapeutics, reported IND-enabling data for ZW49, a novel biparatopic HER2-targeted ADC, at the San Antonio Breast Cancer Symposium in San Antonio, TX (Press release, Zymeworks, DEC 8, 2018, View Source [SID1234531961]).

"These data highlight the potential efficacy of ZW49 versus leading HER2 ADCs and demonstrate the power of combining our therapeutic platforms to achieve greater efficacy and tolerability, thereby increasing the therapeutic window," said Ali Tehrani, Ph.D., President and CEO of Zymeworks. "With the recent submission of our IND for ZW49 we are pleased with the speed and trajectory of ZW49’s development and look forward to starting clinical trials in early 2019."

ZW49 is a HER2-targeted bispecific ADC that capitalizes on the unique geometry and antibody framework of Zymeworks’ lead clinical candidate, ZW25, and is armed with the Company’s proprietary ZymeLink-cytotoxic payload. This design results in enhanced internalization and delivery of the cytotoxin to cancer cells. In preclinical studies, ZW49 demonstrated complete tumor regressions in a panel of high and low HER2-expressing patient derived xenografts and promising efficacy in a model of breast cancer brain metastases. These results compared favorably when benchmarked against approved and leading HER2 ADCs in clinical development. Importantly, efficacy was observed at exposures that were well tolerated in preclinical studies suggesting a broad therapeutic window.

The poster is available through the conference website or through Zymeworks’ website at View Source

About the Azymetric Platform

The Azymetric platform enables the transformation of monospecific antibodies into bispecific antibodies, giving the antibodies the ability to simultaneously bind two different targets. This unique technology enables the development of multifunctional biotherapeutics that can block multiple signaling pathways, recruit immune cells to tumors, enhance receptor clustering degradation, and increase tumor-specific targeting. These features are intended to enhance efficacy while reducing toxicities and the potential for drug resistance. Azymetric bispecifics have been engineered to retain the desirable drug-like qualities of naturally occurring antibodies, including low immunogenicity, long half-life and high stability. In addition, they are compatible with standard manufacturing processes with high yields and purity, potentially significantly reducing drug development costs and timelines.

About the ZymeLink Platform

The ZymeLink platform is a modular suite of site-specific conjugation technologies, customizable linkers, and proprietary cytotoxic payloads designed for the targeted delivery of therapeutics with optimal tolerability and efficacy. The ZymeLink platform is compatible with traditional antibodies and with the Azymetric platform and is intended to facilitate the development of next-generation antibody-drug conjugates with broad therapeutic windows.

Context Therapeutics Announces New Preclinical Data on Apristor at San Antonio Breast Cancer Symposium

On December 8, 2018 Context Therapeutics, a clinical-stage biotechnology company, reported new preclinical data on Apristor (onapristone extended release), its first-in-class full progesterone receptor antagonist, showing that the investigational medicine inhibits tumor cell line growth in hormone receptor positive (HR+) breast cancer cell lines (Press release, Context Therapeutics, DEC 8, 2018, View Source [SID1234531939]). Additionally, it was shown that Apristor is synergistic with current standard of care therapies for HR+ metastatic breast cancer, including the Cdk4/6 inhibitor Ibrance (palbociclib) and the selective estrogen receptor degrader Faslodex (fulvestrant).

"Progesterone receptor is the forgotten target", said Carol Lange, PhD, Professor of Medicine at the University of Minnesota and principal investigator of the research presentation. "HR+ breast cancer is driven by two hormones, estrogen and progesterone. While there are over half a dozen approved medicines to block estrogen and estrogen-related signaling, there are no FDA approved medicines in cancer to block progesterone. The data presented shows that blocking progesterone-related signaling via Apristor is not only active alone in tumor models but it also enhances the activity of medicines that either directly or indirectly target estrogen."

The data presented shows that:

Progesterone / progesterone peceptor (PR) is a unique target distinct from estrogen / estrogen receptor

PR is critical for in vitro growth of HR+ breast cancer cells

PR antagonism via Apristor reduces the expression of cancer promoting genes

PR antagonism is synergistic with Cdk4/6 inhibitors and a SERD

"We are encouraged by these new preclinical data, which speak to the important role PR plays in facilitating HR+ breast cancer disease progression," said Deepak Lala, PhD, Chief Technology Officer of Context. "This is the first study to show that PR antagonism is synergistic with new treatment modalities, including Cdk4/6 inhibition. "

About Apristor

Apristor (onapristone extended release) is Context’s wholly owned, first-in-class, orally active extended release formulation of onapristone, a full progesterone receptor antagonist. Progesterone receptor [PR] plays a critical role in facilitating breast cancer disease progression as well as therapeutic resistance to first line antiestrogen and/or Cdk4/6 inhibitor therapies. Apristor is the only full PR antagonist that is being developed to target breast cancer. Apristor has the potential to transform the treatment of breast cancer, through the potent inhibition of PR signaling thereby blocking breast cancer cell proliferation and overcoming resistance to first line antiestrogen and Cdk4/6 inhibitor therapy.