On October 22, 2018 Athenex (Nasdaq: ATNX), a global biopharmaceutical company dedicated to the discovery, development and commercialization of novel therapies for the treatment of cancer and related conditions, reported the presentation of encouraging efficacy and safety data of Oraxol in the treatment of metastatic breast cancer patients who failed previous chemotherapies in a pharmacokinetics (PK) and phase II clinical trial conducted in Taiwan (Press release, Athenex, OCT 22, 2018, View Source;p=RssLanding&cat=news&id=2372632 [SID1234530108]). The data were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress on October 21, 2018 in Munich, Germany. Oraxol is an innovative oral formulation of paclitaxel, a very effective and commonly used anti-cancer chemotherapy, combined with HM30181A (a novel gastrointestinal tract specific P-glycoprotein pump inhibitor).

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Tumor Response
Tumor Response

Results from twenty four patients with metastatic breast cancer were reported. Common metastatic sites included bone (n=12), liver (n=9), lungs (n=9), lymph nodes (n=9) and 6 patients had > 3 metastasis. These patients failed a median of two previous chemotherapies.

Eleven patients (45.8%) achieved partial remission (PR), 10 patients (41.7%) had stable disease (SD) (two patients with SD will have their last CT scans conducted in early November and therefore, the overall PR rate may be higher), and 3 patients had progressive disease (PD), as shown in the waterfall plot of tumor responses below:

A photo accompanying this announcement is available at View Source

Note that two patients with PD showed small tumor size changes of <30% but were classified as PD because new metastatic lesions were identified by CT scans (* indicates the two patients). Two SD patients are expected to complete their last CT scans in early November and the overall PR rate may be higher in the final analysis.

Drug-related serious adverse events consisting of Grade 4 neutropenia were observed in 3 patients and all recovered completely. There was no dose-limiting neuropathy observed. The Oraxol pharmacokinetic profiles at week 1 were reproducible at week 4, and the plasma AUC exposure is similar to those reported for intravenous paclitaxel at 80mg/kg weekly.

Dr. Rudolf Kwan, Chief Medical Officer of Athenex, stated, "The encouraging pharmacokinetic profile and the positive Phase II clinical efficacy and safety data showed the excellent potential of Oraxol. We are advancing our Phase III program rapidly."

Dr. Ko-Chung Lin, Chief Executive Officer of PharmaEssentia, the licensee of Oraxol for Taiwan, Singapore and Vietnam, commented, "Athenex has been an excellent partner to PharmaEssentia. We have been working closely together on the clinical studies and on our discussions with the regulatory authorities. We are delighted to see such a wonderful set of encouraging results and we are fully committed to support the development of Oraxol in the territory we have licensed from Athenex."

The Orascovery program was initially discovered by Hanmi Pharmaceuticals and licensed to Athenex. PharmaEssentia Corporation (Taiwan Stock Exchange: 6446), licensed the Taiwan, Singapore and Vietnam commercialization rights of Oraxol from Athenex and is a close partner, particularly in the clinical developments of Oraxol in Taiwan.

On October 22, 2018 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported that preliminary clinical data from an ongoing Phase 1 trial of its investigational PARP inhibitor, pamiparib, in combination with low-dose temozolomide in patients with locally advanced or metastatic solid tumors were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress, being held in Munich, Germany (Press release, BeiGene, OCT 22, 2018, View Source;p=irol-newsArticle&ID=2372634 [SID1234530033]). Discovered by BeiGene scientists in Beijing, pamiparib is currently in Phase 3 trials globally and in China as a monotherapy and in Phase 1/2 trials in combination with chemotherapy or immunotherapy for a variety of solid tumors.

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"In prior non-clinical studies, pamiparib has been shown to not only inhibit PARP from repairing damaged DNA, but also trap PARP on DNA undergoing repair, which we believe furthers its potential for anti-tumor activity. This study evaluates the combination of low-dose temozolomide, a DNA damaging agent, with full-dose pamiparib to assess the potential for PARP trapping, and is part of our effort to advance the global development of pamiparib as both a monotherapy and in combination," commented Amy Peterson, M.D., Chief Medical Officer for Immuno-Oncology of BeiGene.

"Preliminary results demonstrate antitumor activity across a variety of indications and regardless of known BRCA mutation status. That, combined with the preliminary safety and tolerability profile, support the continued development of this combination," said Melissa Johnson, M.D., Associate Director, Lung Cancer Research Program, Sarah Cannon Research Institute and lead author of the poster presentation.

Summary of Preliminary Results

This open-label, multi-center Phase 1b dose-escalation trial of pamiparib plus low- dose temozolomide (TMZ) (NCT03150810) was designed to evaluate the safety, tolerability, maximum tolerated dose (MTD), and preliminary antitumor activity of the combination in patients with locally advanced and metastatic tumors. Patients received full-dose pamiparib (60mg twice a day) in combination with escalating doses of TMZ, administered in both pulse and continuous dosing schedules.

As of August 24, 2018, a total of 40 patients with solid tumors have been enrolled in the study. The most frequent tumor types were prostate cancer (n=7), small cell lung cancer (n=6), breast cancer (n=4), epithelial ovarian cancer (n=4), and pancreatic cancer (n=3). Patients had received a median of four prior lines of therapy (1-10). The median duration of treatment was 1.6 months (0-9). As of the data cutoff, a total of 18 patients (45%) remained on pamiparib and TMZ treatment.

The combination was shown to be generally well tolerated. Dose-limiting grade 4 neutropenia was observed in two patients treated with 120 mg TMZ Days 1-7 and two patients treated with 100 mg TMZ Days 1-7. The most common treatment-emergent adverse events (TEAEs), regardless of grade or attribution, were nausea (52.5%), anemia (37.5%), neutropenia (30%), thrombocytopenia (27.5%), and fatigue (27.5%). TEAEs grade ≥3 occurred in 18 patients. The most common grade 3 or 4 adverse events (AEs) were neutropenia (27.5%), anemia (22.5%), and thrombocytopenia (20%). Cytopenias were manageable and reversible. Two patients experienced AEs that resulted in discontinuation of pamiparib and TMZ, one of which was considered related to study treatment. Serious AEs considered related to study treatment occurred in four patients (neutropenia, abdominal abscess, thrombocytopenia and leukopenia, and dehydration). There were no AEs with fatal outcome.

Twenty-three patients with solid tumors other than prostate cancer were evaluable per RECIST v1.1 (defined as having at least one post-baseline tumor assessment or at least nine weeks of follow-up). Preliminary data showed that two patients achieved a confirmed partial response (PR), including one patient with pancreatic cancer (treated with 40 mg TMZ Days 1-28), and one patient with small cell lung cancer (80 mg TMZ Days 1-7). Two additional patients achieved an unconfirmed PR, including one patient with BRCA-mutated triple-negative breast cancer treated with 80 mg TMZ Days 1-7, and one patient with urothelial cancer treated with 40mg TMZ Days 1-7. Ten patients had a best response of stable disease (SD); four patients had a best response of disease progression; and five patients were not evaluable for RECIST response either due to lack of a post-baseline tumor assessment or non-measurable disease at baseline.

All seven patients with prostate cancer were evaluated per the Prostate Cancer Working Group 2 (PCWG2) criteria. Of these, one patient (confirmed BRCA wildtype) achieved a visceral PR and prostate-specific antigen (PSA) response at the first post-baseline tumor assessment, and one patient achieved SD, who remains on study for over 270 days.

About Pamiparib
Pamiparib (BGB-290) is an investigational inhibitor of PARP1 and PARP2 which has demonstrated pharmacological properties such as brain penetration and PARP-DNA complex trapping in preclinical models. Discovered by BeiGene scientists in Beijing, pamiparib is currently in global clinical development as a monotherapy and in combination with other agents for a variety of solid tumor malignancies.

On October 22, 2018 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported positive results from the Phase III IMpower130 study of Tecentriq (atezolizumab) plus chemotherapy (carboplatin and Abraxane [albumin-bound paclitaxel; nab-paclitaxel]) for the initial (first-line) treatment of people with previously untreated metastatic non-squamous non-small cell lung cancer (NSCLC) (Press release, Hoffmann-La Roche, OCT 22, 2018, View Source [SID1234530310]). The analysis showed that Tecentriq plus chemotherapy helped people live significantly longer compared to chemotherapy alone (median overall survival [OS] =18.6 versus 13.9 months; hazard ratio [HR]=0.79; 95% CI: 0.64–0.98; p=0.033) in the intention-to-treat wild-type (ITT-WT) population.[1] The Tecentriq-based combination also significantly reduced the risk of disease worsening or death (progression-free survival; PFS) compared to chemotherapy alone (median PFS=7.0 versus 5.5 months; HR=0.64; 95% CI: 0.54–0.77; p<0.0001) in the ITT- WT population.1 Safety for the Tecentriq plus chemotherapy combination appeared consistent with the known safety profile of the individual medicines, and no new safety signals were identified with the combination.

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"Initial treatment with this Tecentriq-based combination provided a significant survival benefit for people with non-squamous non-small cell lung cancer, the most common form of lung cancer," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "Lung cancer is a complex disease and this combination could offer a new potential treatment option. We will work with global health authorities to bring this regimen to people living with this disease as soon as possible."

The data will be presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress on 22 October 2018, 09:15–09:30 am; Hall A1 – Room 17 (Abstract LBA53).

About the IMpower130 study
IMpower130 is a Phase III, multicentre, open-label, randomised study evaluating the efficacy and safety of Tecentriq in combination with carboplatin and nab-paclitaxel versus chemotherapy (carboplatin and nab-paclitaxel) alone for chemotherapy-naïve patients with stage IV non-squamous NSCLC. The study enrolled 723 people who were randomised (2:1) to receive:

Tecentriq plus carboplatin and nab-paclitaxel (Arm A), or
Carboplatin and nab-paclitaxel (Arm B, control arm)
During the treatment-induction phase, people in Arm A received Tecentriq and carboplatin on day 1 of each 21-day cycle, and nab-paclitaxel on days 1, 8 and 15 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit, whichever occurs first. People received Tecentriq during the maintenance treatment phase until loss of clinical benefit was observed.

During the treatment-induction phase, people in Arm B received carboplatin on day 1 and nab-paclitaxel on days 1, 8 and 15 of each 21-day cycle for 4 or 6 cycles or until disease progression, whichever occurs first. People received best supportive care during the maintenance treatment phase. Switch maintenance to pemetrexed was also permitted. People who were consented prior to a protocol revision were given the option to crossover to receive Tecentriq as monotherapy until disease progression.

The co-primary endpoints were:

PFS as determined by the investigator using RECIST v1.1 in the ITT-WT population
OS in the ITT-WT population
IMpower130 met its co-primary endpoints of OS and PFS.

A summary of the results is included below:

Safety for the Tecentriq and chemotherapy combination appeared consistent with the known safety profile of the individual medicines, and no new safety signals were identified with the combination. Grade 3 – 4 treatment-related adverse events (AEs) were reported in 73.2% of people receiving Tecentriq plus chemotherapy compared to 60.3% of people receiving chemotherapy alone. The most common Grade 3 – 4 AEs in people receiving Tecentriq plus chemotherapy were: an abnormal low count of a certain type of white blood cell (neutropenia, 32.1%), a decrease in red blood cells (anaemia, 29.2%), and a decreased neutrophil count (12.1%).

About NSCLC
Lung cancer is the leading cause of cancer death globally.[2] Each year 1.76 million people die as a result of the disease; this translates into more than 4,800 deaths worldwide every day.[2] Lung cancer can be broadly divided into two major types: NSCLC and small cell lung cancer. NSCLC is the most prevalent type, accounting for around 85% of all cases.[3] NSCLC comprises non-squamous and squamous-cell lung cancer, the squamous form of which is characterised by flat cells covering the airway surface when viewed under a microscope.[3]

About Tecentriq
Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T cells. Tecentriq has the potential to be used as a foundational combination partner with cancer immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers.

Currently, Roche has eight Phase III lung cancer studies evaluating Tecentriq alone or in combination with other medicines.

Tecentriq is already approved in the European Union, United States and more than 70 countries for people with previously treated metastatic NSCLC and for certain types of untreated or previously treated metastatic urothelial carcinoma (mUC).

On October 22, 2018 GTx, Inc. (Nasdaq: GTXI) reported financial results for the third quarter ended September 30, 2018, and provided a corporate update (Press release, GTx, OCT 22, 2018, View Source [SID1234530034]).

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"During the quarter, we turned our focus to the ongoing selective androgen receptor degrader program and the potential of our novel selective androgen receptor degrader to treat castration-resistant prostate cancer. We expect to select the most appropriate development compounds by year-end, which we plan to take into IND-enabling studies next year," said Robert J. Wills, Ph.D., Executive Chairman of GTx. "Additionally, we are exploring other strategic options for the company with the goal of optimizing the full potential of our development pipeline."

Corporate Development Update

Selective Androgen Receptor Degrader (SARD): Prostate Cancer

The Company has an ongoing preclinical program to evaluate its novel selective androgen receptor degrader (SARD) technology in castration-resistant prostate cancer (CRPC). In some men with CRPC, current prostate cancer therapy is not effective or subject to emerging resistance. The Company believes that its SARDs may be first-in-class dual-interacting androgen receptor (AR) antagonists and degraders, and may therefore potentially treat CRPC in men who are non-responsive to current androgen targeted therapies. Going forward, the Company plans to:

Complete ongoing mechanistic preclinical studies by year-end or early in the first quarter of 2019;
Select the most appropriate SARD compounds to move forward with IND-enabling studies in 2019; and
Potentially advance one of its SARD compounds into a first-in-human clinical trial in 2020
Selective Androgen Receptor Modulator (SARM): Stress Urinary Incontinence (SUI), Breast Cancer

SUI: Enobosarm, a SARM, was evaluated in post-menopausal women with SUI compared to placebo. During the quarter, the Company announced that the ASTRID Trial, a Phase 2 double-blind, placebo-controlled clinical trial of orally-administered enobosarm (3 mg or 1 mg) in post-menopausal women with SUI, did not achieve statistical significance on the primary endpoint for the trial. Enobosarm was generally safe and well tolerated, and reported adverse events were minimal and similar across all treatment groups. The Company is conducting a comprehensive review of all the ASTRID data and is consulting with key experts to fully understand the study outcomes.

Advanced Breast Cancer: Enobosarm was also evaluated as a hormonal therapy for women with estrogen receptor positive (ER+) and androgen receptor positive (AR+) breast cancer in a Phase 2 clinical trial. The trial met the primary efficacy endpoint in the trial; there are three women in the study who continue to respond to treatment after almost two years on enobosarm (two have stable disease, one now has a partial response). Approximately one year ago, the Company determined that treatment paradigms had shifted to immunotherapies and/or combination therapies, and that it was no longer feasible for GTx to conduct further development of enobosarm in breast cancer.

Enobosarm has been evaluated in more than two dozen clinical trials enrolling over 2,200 subjects, in which approximately 1,500 subjects were treated with enobosarm at doses ranging from 0.1 mg to 100 mg. At all evaluated dose levels, enobosarm was observed to be generally safe and well tolerated.

Third Quarter 2018 Financial Results

As of September 30, 2018, cash and short-term investments were $38.1 million compared to $43.9 million at December 31, 2017.
Research and development expenses for the quarter ended September 30, 2018 were $7.5 million compared to $5.9 million for the same period of 2017.
General and administrative expenses for the quarter ended September 30, 2018 were $2.2 million compared to $2.6 million for the same period of 2017.
The net loss for the quarter ended September 30, 2018 was $9.4 million compared to a net loss of $8.5 million for the same period in 2017.
Net loss for the nine months ended September 30, 2018 was $33.0 million compared to a net loss of $21.2 million for the same period in 2017.
GTx had approximately 24.1 million shares of common stock outstanding as of September 30, 2018. Additionally, there are warrants outstanding to purchase approximately 5.3 million shares of GTx common stock at an exercise price of $8.50 per share and approximately 3.3 million shares of GTx common stock at an exercise price of $9.02.

On October 22, 2018 Anaeropharma Science Inc. headquartered in Tokyo (hereinafter "Anaeropharma") reported that Anaeropharma Science and Chugai Pharmaceutical Co., Ltd. headquartered in Tokyo (hereinafter "Chugai") have concluded a collaborative research agreement concerning the creation of novel oncology drugs utilizing characteristic features of Bifidobacterium longum through Anaeropharma’s proprietary platform technology, "in situ Delivery and Production System" (hereinafter "i-DPS") (Press release, Anaeropharma Science, OCT 22, 2018, View Source [SID1234530116]). An overview of the contract follows.

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A collaborative research agreement concerning the creation of novel oncology drugs utilizing i-DPS technology

Under the agreement, Anaeropharma and Chugai conduct joint research regarding specific oncology substances by use of Anaeropharma’s i-DPS technology and Chugai’s technology. The scope of the agreement is limited to the specific substances predetermined by both companies, and the i-DPS technology will be applied only to those substances.

About i-DPS and its development programs

Bifidobacterium is obligatory anaerobe which exists as enteroflora in the human body, and known as nonpathogenic bacteria. Solid cancers have immature vascular constructs and their interstitial tumors are in the state of hypoxia. The company aims to leverage the recombinant Bifidobacterium technology to create a new class of anti-cancer drugs. The technology offers broad potential of being more effective to solid tumors and generates oncology drugs with less risks of adverse events than conventional anti-cancer drugs.

The leading product developed using i-DPS technology, APS001F, a recombinant Bifidobacterium to express Cytosine Deaminase which converts a prodrug, 5-FC, to an anti-cancer drug, 5-FU, is under a phase 1 clinical trial in the U.S.