On April 1, 2019 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported the initial results from a Phase Ib study evaluating the efficacy and safety for the combination of ipatasertib, Tecentriq (atezolizumab) and chemotherapy (paclitaxel or nab-paclitaxel (Abraxane [paclitaxel albumin-bound particles for injectable suspension]) as a first-line treatment option for people with advanced triple-negative breast cancer (TNBC) (Press release, Hoffmann-La Roche, APR 1, 2019, View Source [SID1234534809]). Combination treatment demonstrated a confirmed objective response rate (ORR) of 73% (95% CI 53-88%), irrespective of tumour biomarker status. The median duration of follow-up was 6.1 months (range 3.1–10.6). Grade ≥3 adverse events occurred in 14 people (54%); the most common all-grade adverse events were diarrhea (88%; grade ≥3 19%) and rash (69%; grade ≥3 27%).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are enthusiastic about the potential of this combination in triple-negative breast cancer, an aggressive type of breast cancer," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "These early results support the contribution of ipatasertib to our combination treatment approach in TNBC and reinforce our vision to develop medicines that may benefit patients with this challenging disease."

Preliminary efficacy data for the first 26 patients (18 paclitaxel, 8 nab-paclitaxel) show confirmed responses in 19/26 patients, giving a confirmed ORR of 73%. Responses were seen irrespective of PD-L1 status (9/11 [82%] PD-L1+; 6/8 [75%] PD-L1–; 4/7 [57%] PD-L1 unknown) or PIK3CA/AKT1/PTEN alteration status (5/7 [71%] Dx+, 9/11 [82%] Dx–; 5/8 [63%] Dx unknown).

Activation of the PI3K/AKT pathway has been implicated in resistance to chemotherapies and hormonal therapies in multiple tumour types and loss of PTEN, a negative regulator of AKT, has emerged as a potential mechanism for resistance to checkpoint inhibitor therapy. By inhibiting the PI3K/AKT pathway, ipatasertib may contribute to reversal of T-cell-mediated immunotherapy resistance. These results and the potential benefit that ipatasertib plus the Tecentriq/taxane combination may bring to patients are encouraging and add to the Roche development program in triple-negative breast cancer following the approval of the Tecentriq combination.

Trial enrolment for the Phase 1b study is ongoing. Later this year, Roche will initiate a pivotal multi-center, randomised, double-blind Phase III study investigating the combination of ipatasertib, atezolizumab and paclitaxel as first-line therapy for locally advanced/metastatic triple-negative breast cancer.

About the study
The Phase Ib study is an open-label, multicentre study evaluating the safety and efficacy of ipatasertib in combination with atezolizumab and paclitaxel or nab-paclitaxel for patients with locally advanced or metastatic triple-negative breast cancer who have not previously received chemotherapy in the advanced setting. Two triplets: ipatasertib in combination with atezolizumab and paclitaxel (Paclitaxel arm) and ipatasertib in combination with atezolizumab and nab-paclitaxel (nab-Paclitaxel arm) are being evaluated for first-line treatment for advanced TNBC. A second cohort, which is enrolling now, will allow collection of tumour biopsies to assess treatment-related biomarker changes in TNBC patients who have progressed after at least one line of chemotherapy in the advanced setting.

About ipatasertib
Ipatasertib is an oral, highly specific, investigational medicine designed to target and bind to all three isoforms of AKT, which blocks the PI3K/AKT signaling pathway and may prevent cancer cell growth and survival.

Ipatasertib is being studied in tumours that are frequently found to have activation of the PI3K/AKT pathway, including breast and prostate cancers. Pivotal studies are ongoing to evaluate the efficacy and safety of ipatasertib and the opportunity it may provide to address significant unmet needs for patients with these diseases. Ipatasertib has demonstrated clinically meaningful activity in both breast and prostate cancers, with a manageable safety profile.

Ipatasertib was discovered at Genentech in partnership with Array BioPharma Inc.

About Triple-Negative breast cancer
Breast cancer is the most common cancer among women with more than 2 million diagnosed worldwide each year.[1] TNBC represents 15% of all breast cancers and is more common in women under the age of 50, compared with other forms of breast cancer.[2;3;4] It is defined by the lack of expression and/or amplification of the targetable receptors for oestrogen, progesterone and HER2 amplification.[5] Patients with metastatic TNBC generally experience rapid progression and shorter overall survival (OS) compared to other subtypes of breast cancer.[3]

About Roche in breast cancer
Roche has been advancing breast cancer research for more than 30 years with the goal of helping as many people with the disease as possible. Our medicines, along with companion diagnostic tests, have contributed to bringing breakthrough innovations in the HER2 -positive breast cancer. As our understanding of breast cancer biology rapidly improves, we are working to identify new biomarkers and approaches to treatment for all forms of early and advanced breast cancer, including triple-negative and hormone receptor-positive.

Our targeted medicines Herceptin, Perjeta and Kadcyla are continuing to transform the treatment of early and advanced HER2-postive breast cancer and, through our Tecentriq and ipatasertib clinical programmes, we hope to bring new treatment combinations to people with breast cancer, ultimately improving outcomes.

In the United States Tecentriq in combination with nab-paclitaxel is approved for treatment of PD-L1-positive metastatic triple-negative breast cancer. Roche currently has seven phase III studies in TNBC.

On April 1, 2019 TLC (Nasdaq: TLC, TWO: 4152), a clinical-stage specialty pharmaceutical company dedicated to the development and commercialization of novel nanomedicines designed to target areas of unmet medical need in osteoarthritis, pain management, ophthalmology and oncology, reported financial results for the fourth quarter and full year ended December 31, 2018, and provided a business update (Press release, Taiwan Liposome Company, APR 1, 2019, View Source;p=irol-newsArticle&ID=2392882 [SID1234534828]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We had a transformative year in 2018, highlighted by outstanding results from the Phase II clinical trial of our lead program TLC599 for knee osteoarthritis pain, commencement of the first-in-human clinical trial of TLC590 for postsurgical pain management, and completion of a U.S. public offering on Nasdaq," said TLC President George Yeh. "As we move into 2019, we expect to continue to deliver strong progress in our clinical pipeline and company operations by further advancing our lead product candidates closer to pivotal clinical stages while capitalizing on strategic opportunities with our scalable manufacturing capabilities."

Clinical Pipeline Update and Upcoming Milestones

Phase II trial top-line data readout of TLC599 for knee osteoarthritis pain showed significant reductions in pain that sustained through 24 weeks. TLC599 demonstrated statistically significant improvements over placebo, both through 12, 16, 20, and 24 weeks and at every scheduled visit on week 1, 4, 8, 12, 16, 20, and 24. Over half of the patients treated with TLC599 maintained at least a 30% reduction in pain – over twice as many as placebo – throughout the study.

Phase I/II trial top-line data readout of TLC590 for post-surgical pain showed statistically significant and clinically meaningful improvement over the standard of care through 96 hours. In this first-in-human study of TLC590 in patients following inguinal hernia surgery, greater levels of pain reduction were maintained through the entire 168 hours of the study. In the TLC590 group, 58.3% were opioid-free throughout the study. Among those who used opioids, time to first post-surgical use was four times that of the ropivacaine (standard of care) group, and mean total opioid consumption was 54% less.

First patients dosed in Phase II trial of TLC590. The randomized, double-blind, comparator- and placebo-controlled two-part clinical trial will evaluate the safety, pharmacokinetics, and efficacy of TLC590 compared with ropivacaine and placebo in ~200 patients following bunionectomy. Data from Part 1 is expected mid-2019.

TLC178 received clearance from the FDA to initiate Phase I/II clinical trial in pediatric rhabdomyosarcoma. Recruitment of pediatric patients is scheduled to commence once the optimal dose in adults is identified in an analysis scheduled for the second half of 2019.

TLC178 received EMA orphan drug designation for the treatment of soft tissue sarcoma. The designation provides incentives and scientific advice from the EMA during product development phase and 10 years of marketing exclusivity in the EU following product approval. An orphan designation was previously granted by the US FDA, which provides 7 years of marketing exclusivity in the US following product approval.
Corporate Highlights

Completed U.S. IPO. TLC’s American Depositary Shares began trading on The Nasdaq Global Market under the ticker "TLC" on November 21, 2018, becoming the first Taiwan-based biotech company to be listed on Nasdaq. TLC has been listed on the Taipei Exchange since 2012, where it is consistently ranked in the top 5% among all listed companies in corporate governance evaluations.

Appointment of new Chief Medical Officer. Dr. George Spencer-Green, MD, MS, joined TLC in February 2019, bringing experience from serving as VP and clinical head of Pfizer’s biosimilars development program, and as medical director at the likes of Vertex Pharmaceuticals, Abbot Laboratories, and Enbrel, where he led the development of clinical programs, including Humira for rheumatoid arthritis.

Received an upfront payment in March 2019 as part of the commercialization agreement with 3SBio Inc. TLC is eligible for further regulatory and sales milestone payments, as well as a double-digit share of the potential profits from product sales.

Growing global intellectual property protection with 54 granted patents and 68 applications worldwide as of December 31, 2018.
Fourth Quarter and Full Year 2018 Financial Results

Operating revenue for the fourth quarter of fiscal 2018 was NT$17.4 million (US$0.6 million), a 40% increase compared to NT$12.4 million in the fourth quarter of fiscal 2017. Operating expenses for the fourth quarter of fiscal 2018 was NT$326.8 million (US$10.7 million), a 14.2% increase compared to NT$286.1 million in the fourth quarter of fiscal 2017. Net loss for the fourth quarter of fiscal 2018 was NT$306.7 million (US$10.0 million), compared to a loss of NT$262.6 million in the fourth quarter of 2017, or a net loss of NT$5.23 (US$0.17) per share for the fourth quarter of fiscal 2018, compared to a net loss of NT$4.73 per share for the fourth quarter of fiscal 2017.

Operating revenue for the fiscal year 2018 was NT$62.3 million (US$2.0 million), a 25.6% increase compared to NT$49.6 million in the fiscal year 2017. Operating expenses for the fiscal year 2018 was NT$980.3 million (US$32.0 million), a 3.4% increase compared to NT$948.1 million in the fiscal year 2017. Net loss for the fiscal year 2018 was NT$901.6 million (US$29.5 million), compared to a loss of NT$874.0 million in the fiscal year 2017, or a net loss of NT$14.37 (US$0.47) per share for the fiscal year 2018, compared to a net loss of NT$15.75 per share for the fiscal year 2017.

The Company’s cash and cash equivalents and time deposits with maturity over three months (which are classified as "current financial assets at amortized cost" in the Company’s consolidated financial statements) were NT$1,114.6 million (US$36.4 million) as of December 31, 2018, compared to NT$951.7 million at the end of the fourth quarter of fiscal 2017.

On April 1, 2019 Advaxis, Inc. (NASDAQ: ADXS), a late-stage biotechnology company focused on the discovery, development and commercialization of immunotherapy products, reported updated data from the Phase 1/2 KEYNOTE-046 study in metastatic, castration-resistant prostate cancer (mCRPC) (Press release, Advaxis, APR 1, 2019, View Source [SID1234534844]). This trial is being conducted in conjunction with Merck (known as MSD outside the U.S. and Canada) and is evaluating ADXS-PSA, one of Advaxis’ Listeria monocytogenes (Lm)-based immunotherapies, alone and in combination with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Findings will be highlighted in a poster discussion entitled "Effects of ADXS-PSA with or without Pembrolizumab on Survival and Antigen Spreading in Metastatic, Castration-Resistant Prostate Cancer Patients" at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting underway in Atlanta. The poster discussion will be held today from 1:00-5:00 p.m. ET and will be led by lead author Mark N. Stein M.D., FACS, Associate Professor of Medical Oncology at Columbia University Medical Center.

KEYNOTE-046 is an open-label, multicenter, dose-determining safety and tolerability Phase 1/2 trial of 50 heavily pretreated patients conducted in two parts (Part A and Part B), with a Phase 2 expansion cohort. The objective of the study is to evaluate ADXS-PSA alone (Part A) and in combination with KEYTRUDA (Part B) for primary endpoints that include safety, tolerability and dosing. Secondary endpoints include anti-tumor activity and progression-free survival, and exploratory endpoints include associations between biomarkers of immunologic response (serum PSA) with clinical outcomes.

"There is a pressing need to improve the care and treatment of patients with metastatic, castration-resistant prostate cancer," said Dr. Stein. "Data from 37 patients in the combination arm of KEYNOTE-046 are promising as a median overall survival of 21.1 months was observed. These results compare favorably to standard-of-care therapy and to study results from similar unselected patient populations with bone-predominant disease, which indicates that this combination warrants further investigation."

Key findings from the combination arm of KEYNOTE-046 include the following:

The majority of treatment-related adverse events consisted of transient and reversible Grade 1-2 chills/rigors, fever, hypotension, nausea and fatigue. The combination of ADXS-PSA and pembrolizumab has been well-tolerated, to date, with no additive toxicity observed.
Median overall survival was 21.1 months at data cutoff (February 1, 2019) (95% CI, range 16.0 months to not-yet-reached) in this dataset of 37 patients.
Correlative immune analyses showed T-cell responses against PSA in 75% of subjects and antigen spreading in 85% of subjects.
Broader immune stimulation, including B-cell activation, was observed in the combination arm (n=37) than in the ADXS-PSA monotherapy arm (n=13).
"We are very excited to report the updated ADXS-PSA data today at the AACR (Free AACR Whitepaper) meeting," said Kenneth A. Berlin, President and Chief Executive Officer of Advaxis. "These data show the clinical potential of ADXS-PSA both alone and in combination with KEYTRUDA. It is meaningful that the combination has been well-tolerated in the study population because dose-related toxicities can present challenges for cancer patients, and an additive therapy with a favorable safety and tolerability profile may offer an attractive option for clinicians if developed further in this indication." He concluded, "Based on the prolonged survival data and strong safety profile to date, we believe that continued clinical development of ADXS-PSA in combination with KEYTRUDA is warranted and represents a potentially significant opportunity for Advaxis."

The full abstract is available at www.advaxis.com and the poster will be available on the Company’s website today at 1:00 p.m. ET.

About KEYNOTE-046

KEYNOTE-046 (NCT02325557) is a Phase 1/2 open-label, multicenter, dose-determination and expansion trial that evaluates the safety, tolerability and preliminary clinical activity of ADXS-PSA as monotherapy (Part A; n=14 [13 treated]), and in combination with KEYTRUDA (Part B; n=37) in heavily pretreated patients with progressive and refractory mCRPC.

About ADXS-PSA

ADXS-PSA, one of Advaxis’ Lm-based immunotherapies, utilizes live, attenuated, bioengineered Lm as a vector to deliver PSA directly to antigen presenting cells. Development is being pursued in a clinical trial collaboration and supply agreement with Merck

On April 1, 2019 Sierra Oncology, Inc. (Nasdaq: SRRA), a clinical stage drug development company focused on advancing targeted therapeutics for the treatment of patients with significant unmet needs in hematology and oncology, reported that preclinical data for SRA737+LDG, its Chk1 inhibitor plus non-cytotoxic low dose gemcitabine (LDG), in combination with immunotherapy, are being reported today in a late-breaking oral presentation at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019 being held in Atlanta, Georgia (Press release, Sierra Oncology, APR 1, 2019, View Source [SID1234534861]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Given the limited response rates for anti-PD-L1 drugs in patients with small cell lung cancer (SCLC), better treatment options are sorely needed. Our data, showing durable tumor regressions when combining SRA737+LDG with anti-PD-L1 in a mouse model, warrant further clinical studies to investigate the potential of this approach as a strategy to improve outcomes in our patients," said senior researcher Lauren Averett Byers, M.D., Associate Professor of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center, Houston, Texas.

In the study, SRA737+LDG demonstrated significant anti-tumor activity when combined with anti-PD-L1 in a mouse model of SCLC, resulting in durable tumor regressions. These results were accompanied by an induction of anti-tumor cytotoxic T-cells and M1 macrophages and a corresponding reduction in several pro-tumorigenic cell types in the tumors of drug-treated animals.

"The unique replication stress-inducing properties of SRA737 as potentiated by non-cytotoxic low dose gemcitabine have been previously demonstrated to result in intrinsic anti-tumor activity in multiple preclinical models. These striking new data provide evidence for SRA737+LDG’s activation of innate immune signaling and the establishment of an anti-tumor immune microenvironment that synergizes with immune checkpoint inhibitors," said Dr. Christian Hassig, Chief Scientific Officer, Sierra Oncology. "These findings provide a mechanistic basis for the growing body of evidence highlighting a synergistic interplay between replication stress and anti-tumor immune responses and afford a compelling rationale for evaluating SRA737+LDG with immunotherapy in the clinic."

SRA737 AACR (Free AACR Whitepaper) Late-Breaking Oral Presentation:
Date/Time: Monday, April 1st from 3:00 to 5:00 pm ET
Session: Minisymposium: Late-Breaking Research 2
Title: Combination treatment of the CHK1 inhibitor, SRA737, and low dose gemcitabine demonstrates profound synergy with anti-PD-L1 inducing durable tumor regressions and modulating the immune microenvironment in small cell lung cancer
Authors: Triparna Sen, Carminia M. Della Corte, Snezana Milutinovic, Lixia Diao, Robert J Cardnell, Ryan J. Hansen, Bryan Strouse, Michael P. Hedrick, Christian Hassig, Jing Wang, Lauren A Byers.
Location: Georgia World Congress Center, Room B404

Summary slides from this presentation will be made available on the company’s website at www.sierraoncology.com

About SRA737+LDG
SRA737 is a potent, highly selective, orally bioavailable small molecule inhibitor of Checkpoint kinase 1 (Chk1), a key regulator of cell cycle progression and the DNA Damage Response (DDR). SRA737+LDG is a novel drug combination, where non-cytotoxic low dose gemcitabine acts as a potent inducer of replication stress that potentiates SRA737’s anti-tumor activity.

Phase 1/2 clinical trials of SRA737 as monotherapy (NCT02797964) and in combination with low dose gemcitabine (NCT02797977) in multiple solid tumors (ovarian, prostate, non-small cell lung, squamous (head & neck, anal), colorectal, small cell lung, sarcoma, cervical, anogenital) are ongoing. Sierra has also prepared for a potential clinical study of SRA737 in combination with a PARP inhibitor.

Sierra Oncology retains the global commercialization rights to SRA737.

On April 1, 2019 Mustang Bio, Inc. ("Mustang") (NASDAQ: MBIO), a clinical-stage biopharmaceutical company focused on translating today’s medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases, reported that it has entered into a $20 million debt financing agreement with Horizon Technology Finance Corporation (NASDAQ: HRZN) ("Horizon"), a leading specialty finance company that provides capital in the form of secured loans to venture capital-backed companies in the technology, life science, healthcare information and services and cleantech industries (Press release, Mustang Bio, APR 1, 2019, View Source [SID1234534882]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Fifteen million of the $20 million loan was funded upon closing. The remaining $5 million may be funded upon Mustang achieving certain predetermined milestones. Each advance of the loan will be repaid in 42 monthly payments consisting of 18 monthly payments of interest only, followed by 24 monthly payments of principal and accrued interest, and will be payable monthly in arrears. The interest-only period may be extended to 24 months contingent upon Mustang achieving certain milestones. In connection with the debt financing, Mustang issued Horizon warrants to purchase up to 288,184 of its common shares at an exercise price of $3.47 per share.

"This financing provides Mustang with additional working capital to continue to develop our gene and cell therapies in our cell processing facility in Worcester, Mass., with the goal of bringing potentially life-saving treatments to patients in need," said Manuel Litchman, M.D., President and Chief Executive Office of Mustang. "We are pleased to partner with Horizon, a leading specialty finance company that has an extensive history of supporting innovative life science companies."

Gerald A. Michaud, President of Horizon, stated, "We are delighted to provide this significant loan for Mustang Bio, an exciting company with promising treatments for cancer and rare genetic diseases. With Mustang Bio’s pipeline of cell and gene therapies, the company is poised for success as it works to commercialize its product pipeline."

Torreya Partners served as financial advisor to Mustang in conjunction with this transaction.