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]).

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"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.

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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 Vaccibody AS and Nektar Therapeutics (Nasdaq: NKTR) reported the presentation of new preclinical data for VB10.NEO, a personalized neoantigen cancer vaccine, combined with bempegaldesleukin (NKTR-214 or bempeg), a CD122-preferential IL-2 pathway agonist (Press release, Vaccibody, APR 1, 2019, View Source [SID1234534860]). These data were presented today in a poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019.

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"We are excited to present these novel preclinical data that show combining bempeg with VB10.NEO synergize to increase both the breadth and the depth of the neoantigen-specific immune response. These unique and non-overlapping mechanisms produced an expansion of the VB10.NEO elicited neoantigen-specific T cells and demonstrated enhanced anti-tumor efficacy in mice. We look forward to evaluating this novel immuno-oncology combination in a clinical study in patients with advanced or metastatic squamous cell carcinoma of head and neck later this year," said Agnete B. Fredriksen, Ph.D., Vaccibody’s President and Chief Scientific Officer.

VB10.NEO is designed to specifically activate a patient’s immune system to tumor-specific antigens, called neoantigens. Bempeg is designed to expand and proliferate tumor antigen-specific T cells in the tumor microenvironment. Addition of bempeg to VB10.NEO is intended to drive maximal expansion of vaccine-induced neoantigen-specific T cells for the treatment of cancer.

"Personalized T cell vaccines could play a critical and central role in cancer immunotherapy," said Jonathan Zalevsky, Ph.D., Chief Scientific Officer at Nektar. "These preclinical data highlight the potential of combining a personalized cancer vaccine with a T cell proliferator to induce maximal expansion of vaccine-induced T cell clones and durable responses and specific anti-tumor immunity. We are highly encouraged by these results and look forward to testing this unique approach to personalized cancer treatment in patients with squamous cell carcinoma of the head and neck."

Details of the poster presentation at AACR (Free AACR Whitepaper) are as follows and will be available for download at the time of presentation at View Source and View Source

Abstract #2256
Title: "Combination of neoantigen DNA plasmid vaccine VB10.NEO and NKTR-214, a CD122-biased immunostimulatory cytokine, induces strong neoantigen-specific T cell responses and sustained tumor regression in pre-clinical models"
Session: Clinical Research – Combination Therapies 1
Session Data and Time: Monday, April 1, 2019, 1:00 p.m. – 5:00 p.m. Eastern Time

Combination of VB10.NEO and NKTR-214 synergizes to elicit greater breadth and depth of neoantigen-specific T cell responses than each individual treatment.
The synergistic effect was observed in both CD4 and CD8 T cells, and most pronounced on CD8 T cell responses, further supporting the combination’s potential to induce strong immunogenic CD8+ T cell responses.
VB10.NEO in combination with NKTR-214 and anti-PD-1 induce rapid, complete and durable tumor regression of small tumors and long-lasting stabilization of large tumors supporting the rationale for examining the combination clinically.
In September 2018, Nektar and Vaccibody entered into a clinical collaboration to evaluate bempegaldesleukin in combination with VB10.NEO. A pilot study evaluating the combination in patients with squamous cell carcinoma of the head and neck is planned to begin mid-2019.

About VB10.NEO
VB10.NEO, is a proprietary therapeutic DNA vaccine which uses the patient’s own neoantigens for the personalized treatment of cancer patients. A phase I/IIa neoantigen clinical trial is currently enrolling patients with locally advanced or metastatic melanoma, non-small cell lung carcinoma, clear renal cell carcinoma as well as urothelial cancer or squamous cell carcinoma of the head and neck.

About bempegaldesleukin (NKTR-214)
Bempegaldesleukin is an investigational, first-in-class, CD122-preferential IL-2 pathway agonist designed to provide rapid activation and proliferation of cancer-killing immune cells, known as CD8+ effector T cells and natural killer (NK) cells, without over activating the immune system. Bempegaldesleukin stimulates these cancer-killing immune cells in the body by targeting CD122 receptors found on the surface of these immune cells. CD122, which is also known as the Interleukin-2 receptor beta subunit, is a key signaling receptor that is known to increase proliferation of these effector T cells.1 In clinical and preclinical studies, treatment with bempegaldesleukin resulted in expansion of these cells and mobilization into the tumor micro-environment.2,3 Bempegaldesleukin has an antibody-like dosing regimen similar to the existing checkpoint inhibitor class of approved medicines.

On March 31, 2019 Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a leading off-the-shelf, allogeneic T-cell immunotherapy company developing novel treatments for patients with cancer, autoimmune and viral diseases, reported that the Company’s collaborators at Memorial Sloan Kettering Cancer Center (MSK), Prasad S. Adusumilli, M.D., and Michel Sadelain, M.D., Ph.D., presented encouraging results from an ongoing MSK investigator-sponsored Phase 1 clinical study (NCT02414269) of a mesothelin-targeted CAR T immunotherapy for patients with mesothelin-associated malignant pleural solid tumors, primarily mesothelioma, who progressed following prior standard platinum-containing chemotherapy (Press release, Atara Biotherapeutics, MAR 31, 2019, View Source [SID1234534786]). Mesothelin-targeted, autologous CAR T cells delivered regionally were well-tolerated and showed encouraging anti-tumor activity in combination with pembrolizumab, a PD-1 checkpoint inhibitor. The findings will be presented today in the Advances in Novel Immunotherapeutics oral session at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019 in Atlanta, Georgia.

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"Clinical results presented by our MSK collaborators reaffirm mesothelin as a promising target for patients with advanced mesothelioma and establish an important proof-of-concept advance for CAR T immunotherapy in solid tumors," said Dietmar Berger, M.D., Ph.D., Global Head of Research and Development of Atara Biotherapeutics. "These encouraging safety results and anti-tumor responses observed by lead investigator Dr. Adusumilli in combination with a PD-1 checkpoint inhibitor, support our plans to progress development of a next-generation, mesothelin-targeted CAR T immunotherapy using MSK’s novel 1XX CAR signaling domain and PD-1 dominant negative receptor (DNR) checkpoint inhibition technologies for patients with mesothelin-associated solid tumors."

The Phase 1 clinical study recruited 21 patients, 19 with malignant pleural mesothelioma (MPM), one with metastatic lung cancer and one with metastatic breast cancer, who received a median of 3 prior treatment regimens, to evaluate the safety and potential anti-tumor activity of a CD28-costimulated, mesothelin-targeted autologous CAR T immunotherapy. The study included six dose cohorts with administration directly to the tumor site using regional delivery techniques, initially at a low CAR T dose without lymphodepleting chemotherapy, followed by increasing CAR T dose cohorts with lymphodepletion. A subset of these patients was subsequently treated with pembrolizumab, a PD-1 checkpoint inhibitor.

Mesothelin-targeted, autologous CAR T administration was found to be generally well-tolerated with no CAR T-related toxicities higher than grade 2 observed based on monitoring multiple clinical, radiological, and laboratory parameters. CAR T cells were found to be persistent in the peripheral blood for 13 of the 21 patients during the 38-week evaluation, and their presence was associated with evidence of tumor regression on imaging studies.

Best overall response rate (ORR) for a subset of 11 MPM patients with minimum follow-up time of 3 months who also received pembrolizumab and lymphodepleting chemotherapy was 72% including 2 durable complete metabolic responses (CMR) on PET imaging and 6 partial responses (PR). Six of the 11 patients in this subset were programmed cell death ligand 1 (PD-L1) negative, defined as undetectable expression of PD-L1 in tumor cells by immunohistochemistry, with 4 of the 8 total responses observed in PD-L1 negative patients (1 CMR and 3 PR).

Following progression on standard platinum-containing chemotherapy, the expected ORR for patients with MPM treated with a checkpoint inhibitor is estimated between 5%-29% with one patient achieving a CR across multiple studies.1-5

MSK is also investigating mesothelin-targeted CAR T cells for patients with mesothelin-associated advanced breast cancer (NCT02792114). Additional results from these ongoing studies are expected to be presented at upcoming scientific congresses.

Presentation CT036: A Phase I clinical trial of malignant pleural disease treated with regionally delivered autologous mesothelin-targeted CAR T cells: Safety and efficacy
Session CTMS01: Advances in Novel Immunotherapeutics
Presentation Date and Time:Sunday, March 31, 2019 from 3:20 pm – 3:35 pm EDT
Location:Room A411 – Georgia World Congress Center
Authors:Prasad S. Adusumilli, Marjorie Zauderer, Valerie Rusch, Roisin O’Cearbhaill, Amy Zhu, Daniel Ngai, Erin McGee, Navin Chintala, John Messinger, Alain Vincent, Elizabeth Halton, Claudia Diamonte, John Pineda, Shanu Modi, Steve Solomon, David R Jones, Renier Brentjens, Isabelle Riviere, Michel Sadelain
Affiliations:Memorial Sloan Kettering Cancer Center

On March 31, 2019 F1 Oncology, Inc., a biotechnology company discovering and developing adoptive cellular therapies (ACTs) for solid tumors, reported that it will present four abstracts at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) 2019 Annual Meeting in Atlanta from March 29-April 3, 2019 that support novel technologies to treat solid tumor malignancies (Press release, F1 Oncology, MAR 31, 2019, View Source [SID1234534788]).

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F1 Oncology is developing these novel CAB-CAR-T therapies to target solid tumors while minimizing the potential of on-target, off-tumor activity. The four abstracts provide insight into the use of the company’s proprietary CAB-CAR-T technology to increase the potential safety of CAR-T therapeutics by turning the negative effects of the tumor microenvironment (TME) into activating signals. They will highlight proof of concept studies of same-day, point of care CAR-T and use bioinformatics data driven methods to discover protein domain combinations capable of selectively expanding CAR-T cells.

"The data to be presented highlight scientific progress that may greatly simplify CAR-T therapy for solid tumor malignancies in the future," said Gregory Frost, Ph.D., Chairman and CEO of F1 Oncology. "The teams have also made significant progress in our understanding of CAB-CAR-T’s role in adoptive cellular therapy for solid tumors, and we look forward to seeing the progress from ongoing clinical studies with these programs through collaborators in Shanghai."

The abstracts are available in the program section of the annual AACR (Free AACR Whitepaper) meeting website, and details for the poster presentations are as follows:

Same day transduction and in vivo expansion of chimeric antigen receptors and synthetic driver constructs for adoptive cellular therapy

Examining the relationship between limiting the ex vivo expansion time and less differentiated CAR-T products with enhanced effector function, as well as the development of a point of care approach to ACT and its potential to reduce the complexity of CAR-T cell immunotherapy.

Poster Board Number: Session PO.IM02.03 2327/26

Session Date and Time: April 1, 2019, 1:00 p.m. – 5:00 p.m.

Location: Georgia World Conference Center, Poster Section 22

A high-throughput screening strategy for the identification of novel lymphoproliferative elements

Examining a high throughput screening method using a barcoded high-diversity combinatorial library of various rationally-designed protein subdomains to identify novel combinations capable of selectively driving CAR-T cells in vivo.

Poster Board Number: Session PO.MCB09.05 3523/9

Session Date and Time: April 2, 2019, 8:00 a.m. – 12:00 p.m.

Location: Georgia World Conference Center, Poster Section 22

CAB-CAR-T: A novel conditionally active biologics approach to minimize on-target off-tumor effects in adoptive immunotherapy
Describing a novel Conditionally Active Biologics (CAB) approach in adoptive immunotherapy

Poster Board Number: session PO.IM02.04 3189/12

Session Date and Time: April 2, 2019, 8:00 a.m. – 12:00 p.m.

Location: Georgia World Conference Center, Poster Section 22

CAB-CAR-T: The Prioritization of Cell Surface Protein Targets for Conditionally Active Biologics to Treat All Solid Tumors

Identifying optimal targets across all TCGA cancer cohorts that when used in CAB-CAR-T therapies will provide the greatest number of treatment options for patients across all cancer malignancies.

Poster Board Number: Session PO.BSB01.05 5101/9

Session Date and Time: April 3, 2019, 8:00 a.m. – 12:00 p.m.

Location: Georgia World Conference Center, Poster Section 30