On September 28, 2015 OncoGenex Pharmaceuticals, Inc. (NASDAQ: OGXI) reported results from additional exploratory analyses of the Phase 3 SYNERGY trial demonstrating that custirsen treatment significantly lowered serum clusterin (sCLU) levels from baseline in men with metastatic castrate-resistant prostate cancer (mCRPC) (Press release, OncoGenex Pharmaceuticals, SEP 27, 2015, View Source [SID:1234507580]). In addition, these data presented at the 2015 European Cancer Congress (ECC 2015) in Vienna showed that sCLU reductions after custirsen treatment resulted in higher two-year survival rates in patients who were at increased risk for poor outcomes. Of those patients with lower sCLU levels, the data also showed a correlation to an overall survival benefit for custirsen-treated patients who were at increased risk for poor outcomes.

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"These data support that custirsen is inhibiting the production of clusterin in men with metastatic CRPC and a correlation between treatment-induced reductions in sCLU and clinical benefit in those patients at risk for poor outcomes," said Scott Cormack, President and CEO of OncoGenex. "We look forward to top line results in metastatic CRPC patients at risk for poor outcomes later this year in our Phase 3 AFFINITY trial."

Production of the protein clusterin is a fundamental cellular repair mechanism that tumor cells exploit to evade destruction by anti-cancer therapies. Overproduction of clusterin, which occurs in response to a variety of cancer treatments, is associated with faster rates of cancer progression and shorter survival. Custirsen is a highly specific clusterin inhibitor designed to improve survival in patients with advanced cancer.

A previous retrospective analysis from the SYNERGY trial showed a benefit with custirsen therapy in men with metastatic CRPC who had at least two of five common risk factors for poor prognosis. For those men, a 27 percent lower risk of death occurred when custirsen was used in combination with first-line docetaxel compared to docetaxel alone.

About the Study Results
(Abstract: 2560 – Baseline serum clusterin level in patients with poor prognostic features was associated with response to custirsen treatment: Results from the phase 3 SYNERGY trial of docetaxel +/- custirsen, Monday, September 28, 2015, 16:45 – 18:45 CEST, Hall C)

The analysis presented at ECC 2015 further demonstrates the impact of custirsen treatment on mCRPC patients at increased risk for poor outcomes, including a reduced risk of death among poor prognostic patients who achieved lower sCLU levels (Day 140 Area Under Curve (AUC)) during treatment. Patients in the poor prognostic subgroup who were treated with custirsen and had reduced Day 140 AUC sCLU levels showed a trend for higher two-year survival status. A landmark analysis also showed that overall survival benefit for the custirsen arm appeared greater in the poor prognostic patients who achieved lower Day 140 AUC sCLU levels.

In patients with lower sCLU at baseline, a trend for greater effect of custirsen treatment on survival was also observed, especially in patients at increased risk for poor outcomes. Patients at risk for poor outcomes with low baseline sCLU treated with custirsen (n=176) experienced a median survival of 18.4 months, compared to 14.4 months for patients on the control arm (n=170) [HR=0.689 (95% CI: 0.483-0.983); the median baseline sCLU was 55.30 ug/mL for patients at risk for poor outcomes. In the subpopulation of patients with a good prognosis, patients with low baseline sCLU treated with custirsen (n=171) experienced a median survival of 31.2 months in comparison to 27.2 months for patients on the control arm (n=186) [HR = 0.823 (95% CI: 0.505-1.34); the median baseline sCLU was 53.2 ug/mL for patients with a good prognosis.

Apatorsen Update
(Abstract: 2637 – Baseline circulating tumor cells (CTC) and serum heat shock protein 27 (Hsp27) levels are increased in advanced bladder cancer (BC) patients with poor prognostic factors: Results from the randomized phase 2 Borealis-1TM trial of first-line gemcitabine/cisplatin plus apatorsen or placebo, Monday, September 28, 2015, 16:45 – 18:45 CEST, Hall C)

Results from the company’s other lead product candidate, apatorsen, presented at ECC 2015 confirmed that patients with advanced bladder cancer at increased risk for poor outcomes had increased baseline levels of circulating tumor cells (CTC) and of serum heat shock protein 27 (Hsp27). The study showed that baseline Hsp27 and CTC levels were independent risk factors for survival outcomes.

"Apatorsen is designed to inhibit the production of Hsp27 and thereby to disable cancer cells’ defenses and overcome treatment resistance that is common in this disease," said Cindy Jacobs, PhD, MD, Chief Medical Officer and Executive Vice President of OncoGenex. "Patients in the Borealis-1TM trial with advanced disease who had specific poor prognostic risk factors experienced a clinical benefit with apatorsen. We are continuing to work closely with investigators and regulatory agencies to determine next steps as we collect more evidence regarding apatorsen’s activity in this disease."

Data from the Borealis-1 trial previously reported at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting earlier this year showed that metastatic bladder cancer patients with poor prognostic features (low performance status, liver involvement, low hemoglobin and high alkaline phosphatase) showed a potential survival benefit with apatorsen 600mg added to first-line chemotherapy (HR = 0.72) compared to chemotherapy alone. Patients in the trial with a Karnofsky Performance Status of 80 percent or less, a common indicator of poor prognosis, experienced a 50 percent reduction in risk of death with the addition of apatorsen therapy (HR = 0.50).

Completion of enrollment in the Phase 2 Borealis-2 bladder cancer trial is expected to occur by the end of 2015 and will evaluate apatorsen in combination with docetaxel in patients with advanced or metastatic bladder cancer who have disease progression following first-line platinum-based chemotherapy.

About Clusterin

A major barrier to extending survival in patients with advanced cancer is treatment failure due to the ability of tumor cells to exploit fundamental cellular mechanisms that allow them to evade destruction by anti-cancer therapies. The production of the protein clusterin is a fundamental cellular repair mechanism that tumor cells exploit to evade destruction by anti-cancer therapies. Increased clusterin production has been linked to faster rates of cancer progression, treatment resistance and shorter survival duration in patients.

About Custirsen

Custirsen is a highly specific clusterin inhibitor designed to improve survival in patients with advanced cancer by disabling a fundamental cellular repair mechanism used by tumor cells. Custirsen binds to clusterin mRNA to block the production of clusterin protein and has enhanced the tumor cell destructive effects of multiple anti-cancer therapies across a variety of tumor models. By inhibiting clusterin, custirsen is designed to alter tumor dynamics by slowing tumor growth and inhibiting tumor resistance to partner treatments, so that the benefits of therapy, including survival, may be extended.

Custirsen has Fast Track designation by the U.S. Food and Drug Administration for metastatic CRPC and non-small cell lung cancer.

About Apatorsen and ORCA
Apatorsen (OGX-427) is designed to inhibit production of heat shock protein 27 (Hsp27), disable cancer cells’ defenses and overcome treatment resistance. Hsp27 is an intracellular protein that protects cancer cells by helping them survive, leading to resistance and more aggressive cancer phenotypes. Both the potential single-agent activity and synergistic activity of apatorsen with cancer treatments may increase the overall benefit of existing therapies and augment the durability of treatment outcomes, which could lead to increased patient survival.

The ORCA (Ongoing Studies Evaluating Treatment Resistance in CAncer) program encompasses clinical trials of apatorsen. Phase 2 clinical trials are underway in bladder, lung, pancreatic and prostate cancers. For more information on apatorsen and ORCA, please visit www.OncoGenex.com or www.orcatrials.com.

On September 27, 2015 OncoSec Medical Incorporated ("OncoSec") (NASDAQ: ONCS), a company developing DNA-based intratumoral cancer immunotherapies, reported results from a Phase II trial demonstrating that its investigational therapy, ImmunoPulse IL-12, promotes tumor-specific, systemic anti-tumor immune responses in patients with Merkel cell carcinoma (MCC) (Press release, OncoSec Medical, SEP 27, 2015, View Source [SID:1234507581]). Shailender Bhatia, MD, Assistant Professor of Medicine, Division of Medical Oncology at the University of Washington School of Medicine and Principal Investigator of the trial, presented the findings today in an oral presentation at the 2015 European Cancer Congress in Vienna, Austria.

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"The successful completion of the first prospective trial of immunotherapy in MCC marks an important milestone," said Dr. Bhatia. "Importantly, our findings support the hypothesis that intratumoral IL-12 DNA with electroporation promotes tumor immunogenicity. The results confirm the potential of this approach to make a clinically meaningful impact on patient outcomes for this virus-associated cancer."

In this Phase II study, 79% of patients (11/14) showed an increase in IL-12 protein levels in tumor biopsy samples obtained approximately 22 days after treatment compared to baseline, indicating that ImmunoPulse IL-12 leads to successful DNA transfection and sustained protein expression within the tumor microenvironment. ImmunoPulse IL-12 was well-tolerated, with no treatment-related adverse events above Grade 2 and no treatment-related serious adverse events. The most common adverse event was Grade 1 transient pain associated with the treatment procedure.

Analysis of individual lesions found that 30% of patients (3/10) who were evaluable for systemic anti-tumor immunity had regression of at least one distant, non-injected/non-electroporated lesion. In patients considered evaluable for objective response by modified RECIST criteria (i.e., Cohort B, N=12), 25% of patients (3/12) had an objective partial response (PR) and one patient had stable disease (SD) for a disease control rate (PR + SD) of 33%. In Cohort A (N=3), one patient had a pathologic complete response and continues to be recurrence-free at six months. Another patient has been recurrence-free for over three years. Immune correlative data suggest that ImmunoPulse IL-12 can increase tumor-infiltrating lymphocytes and may promote a tumor-specific CD8+ T-cell response.

"We are very excited to observe that ImmunoPulse IL-12 continues to demonstrate that intratumoral treatment with IL-12 DNA and electroporation can induce anti-tumor immune effects both locally and systemically," said Mai H. Le, MD, Chief Medical Officer at OncoSec. "These results are consistent with what we have previously observed in metastatic melanoma and underscore the broad-reaching potential of ImmunoPulse IL-12 in driving immunogenicity."

About the Phase II Study Design
OMS-I110 was a Phase II open-label study that enrolled 15 patients with MCC. The primary endpoint of the trial was IL-12 protein expression following treatment with ImmunoPulse IL-12. Secondary endpoints included: safety and tolerability; overall response rate evaluated by RECIST-modified criteria for MCC; distant lesion regression; and biological markers of pro-inflammatory changes in the tumor microenvironment. Modifications to the standard RECIST criteria included permitting more than two measurable lesions per organ (e.g., skin) to be considered evaluable as "target lesions" and the use of a combination of clinical and radiographic measurements for lesion assessment.

Patients enrolled into this study were separated into two cohorts. Cohort A (N=3) was comprised of patients whose disease status was amenable to definitive surgery or radiation following a single cycle of ImmunoPulse IL-12 treatment (i.e., neo-adjuvant). Patients with more advanced disease were enrolled into Cohort B (N=12) and permitted to receive up to four cycles of ImmunoPulse IL-12.

About Merkel Cell Carcinoma (MCC)
MCC is a rare, aggressive cancer with a disease-associated mortality estimated to be three times that of malignant melanoma and affects approximately 1,600 people per year in the US.1-3 The reported incidence has more than tripled over the past 20 years and the health impact of MCC is growing rapidly with a proportional increase in the aging population.2-4 The reported five year relative survival for patients with local, nodal and metastatic disease is 64%, 39% and 18% respectively.1

Treatment options in the metastatic setting are limited for patients. Responses to chemotherapy regimens are usually short-lived and the impact on survival is unclear.5 Also, chemotherapy regimens are associated with toxicity and may not be suitable for MCC patients who tend to be older with multiple co-morbidities.5 Therefore, there is a strong unmet need for biology-driven therapies in MCC.

The recent discovery of the Merkel cell polyomavirus has provided the missing link between MCC and its association with immune suppression.5 MCC tumors are able to evade the immune system by establishing a local immunosuppressive microenvironment. Evidence shows the presence of intratumoral CD8+ T-cells are associated with better prognosis. As such, therapies aimed at promoting intratumoral inflammation may improve MCC patient outcomes.

On September 27, 2015 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported positive results from two phase II studies that evaluated the investigational cancer immunotherapy atezolizumab (anti-PDL1; MPDL3280A) in people with advanced non-small cell lung cancer (NSCLC) (Press release, Hoffmann-La Roche , SEP 27, 2015, View Source [SID:1234507566]). In the randomised phase II study, POPLAR, atezolizumab met its primary endpoint and showed a statistically significant survival benefit compared to chemotherapy (HR=0.54; p=0.014) in people with recurrent NSCLC whose tumours expressed medium and high levels of PD-L1, which corresponded with people living 7.7 months longer than people who received docetaxel chemotherapy. A separate, single-arm phase II study, BIRCH, met its primary endpoint and showed that atezolizumab shrank tumours (objective response rate, ORR) in up to 27 percent (p=0.0001) of people whose disease had progressed on prior medicines and also expressed the highest levels of PD-L1. Median survival had not yet been reached. In both studies of atezolizumab, adverse events (AEs) were consistent with those observed in previous studies.

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"Results from both of our studies in non-small cell lung cancer showed that measuring PD-L1 may help identify people most likely to respond to atezolizumab, and the majority of responses continued when these data were assessed," said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development. "Durable responses are meaningful for people whose cancer has progressed on other medicines, and we plan to submit these results to global health authorities to bring this potential new option to people as soon as possible".

In February 2015, atezolizumab received Breakthrough Therapy Designation from the US Food and Drug Administration (FDA) for the treatment of people whose NSCLC expresses PD-L1 and whose disease worsened during or after standard treatments (e.g. platinum-based chemotherapy and appropriate targeted therapy for EGFR mutation-positive or ALK-positive disease). Roche is discussing these NSCLC data from POPLAR and BIRCH with the FDA as part of its Breakthrough Therapy Designation and with other health authorities around the world. Roche currently has seven ongoing phase III studies of atezolizumab alone or in combination with other medicines for various types of lung cancer.

About the POPLAR study
Full results of the POPLAR study will be presented by Johan Vansteenkiste, University Hospital Leuven, Leuven, Belgium (Abstract #14LBA) on Sunday, 27 September, 09:15 CET.

Atezolizumab monotherapy vs docetaxel in 2L/3L non-small cell lung cancer: Primary analyses for efficacy, safety and predictive biomarkers from a randomized phase II study (POPLAR)

POPLAR is a multicentre, open-label, randomised phase II study evaluating the efficacy and safety of atezolizumab compared with docetaxel in people with recurrent locally advanced or metastatic NSCLC. Patients were randomised to receive either atezolizumab 1200 mg intravenously every three weeks or docetaxel 75 mg/m2 intravenously every three weeks. Treatment with atezolizumab may have been continued as long as people were experiencing clinical benefit as assessed by the investigator, i.e. in the absence of unacceptable toxicity or symptomatic deterioration attributed to disease progression. The study enrolled 287 people with previously treated, advanced NSCLC. The primary endpoint was overall survival (OS); secondary endpoints included progression free survival (PFS), ORR and safety. People were stratified by PD-L1 expression on tumour-infiltrating immune cells (ICs), histology and prior lines of therapy. PD-L1 expression was assessed for both tumour cells (TCs) and ICs; people were scored as TC0, 1, 2 or 3 and IC0, 1, 2 or 3 with an immunohistochemistry (IHC) test being developed by Roche Diagnostics.

About the BIRCH study
Interim results of the BIRCH study will be presented by Benjamin Besse, Institut Gustave Roussy, Villejuif France and Paris Sud University, France (Abstract #16LBA) on Sunday, 27 September, 09:35 Central European Time (CET).

Phase II, single-arm trial (BIRCH) of atezolizumab as first-line or subsequent therapy for locally advanced or metastatic, PDL1-selected NSCLC

BIRCH is an open-label, multicentre, single-arm phase II study that evaluated the safety and efficacy of atezolizumab in 667 people with locally advanced or metastatic NSCLC whose disease expressed

PD-L1. PD-L1 expression was assessed for both TCs and tumour-infiltrating ICs with an investigational immunohistochemistry test (IHC) being developed by Roche Diagnostics. Eligibility criteria included people whose tumours were determined to express PD-L1 with an IHC score of TC2/3 or IC2/3. People in the study received a 1200 mg intravenous dose of atezolizumab every three weeks. The primary endpoint of the study was the ORR assessed by independent review facility per RECIST v1.1. Secondary endpoints included duration of response, OS, PFS and safety.

About atezolizumab
Atezolizumab (anti-PDL1; MPDL3280A) is an investigational monoclonal antibody designed to interfere with a protein called PD-L1. Atezolizumab is designed to target PD-L1 expressed on TCs and tumour-infiltrating ICs, preventing it from binding to PD-1 and B7.1 on the surface of T cells. By inhibiting PDL1, atezolizumab may activate T cells.

All studies of atezolizumab include the evaluation of an investigational IHC test that uses the antibody SP142 to measure PD-L1 expression on both TCs and tumour-infiltrating ICs. The goal of PD-L1 as a biomarker is to identify those people most likely to benefit when treated with atezolizumab alone, and to determine which people may benefit most from a combination of atezolizumab and another medicine. There are 11 ongoing or planned phase III studies of atezolizumab across certain kinds of lung, kidney, breast and bladder cancers.

About non-small cell lung cancer
Lung cancer is the leading cause of cancer death globally. Each year 1.59 million people die as a result of the disease; this translates into more than 4,350 deaths worldwide every day. 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 percent of all cases.

On September 27, 2015 Roche (SIX: RO, ROG; OTCQX: RHHBY) treported early results from a pivotal phase II study, IMvigor 210, of the investigational cancer immunotherapy atezolizumab (anti-PDL1; MPDL3280A) in people with locally advanced or metastatic urothelial carcinoma (mUC) (Press release, Hoffmann-La Roche , SEP 27, 2015, View Source [SID:1234507567]). The study showed that atezolizumab shrank tumours (objective response rate, ORR) in 27 percent of people with mUC whose disease had medium and high levels of PD-L1 expression and worsened after initial treatment. Ninety-two percent of people who responded to atezolizumab continued to respond when the results were assessed. Median duration of response was not yet reached. Adverse events were consistent with those observed in previous studies.

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"These results may represent the first major treatment advancement in advanced bladder cancer in nearly 30 years," said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development. "We are encouraged that responses to atezolizumab were ongoing in the large majority of people when the study results were assessed."

Roche is planning to submit these data to global health authorities and to the FDA under a Breakthrough Therapy Designation for the treatment of people whose metastatic bladder cancer expresses PD-L1. This designation is designed to expedite the development and review of medicines intended to treat serious diseases that may demonstrate substantial improvement over existing therapies.

About the IMvigor 210 study
These final results from cohort 2 of this study (minimum of 24 weeks’ follow-up) will be presented in an oral session presentation by Jonathan E. Rosenberg, MD, Memorial Sloan Kettering Cancer Center, USA (Abstract #21LBA) on Sunday, 27 September, 10:40 Central European Time (CET).

Atezolizumab in patients (pts) with locally-advanced or metastatic urothelial carcinoma (mUC): Results from a pivotal multicenter phase II study (IMvigor 210).

IMvigor 210 is an open-label, multicentre, single-arm phase II study that evaluated the safety and efficacy of atezolizumab in people with locally advanced or mUC, regardless of PD-L1 expression. People in the study were enrolled into one of two cohorts. Cohort 1 consisted of people who had received no prior therapies for locally advanced or mUC, but who were ineligible for first-line cisplatin-based therapy; results for this cohort are not yet mature. Cohort 2, for which results were announced today, included people whose disease had progressed during or following previous treatment with a platinum-based chemotherapy regimen. People received a 1200-mg intravenous dose of atezolizumab on day one of 21-day cycles until progressive disease (Cohort 1) or loss of clinical benefit (Cohort 2).

The primary endpoint of the study was ORR. Secondary endpoints included duration of response (DoR), overall survival (OS), progression-free survival (PFS) and safety. People were selected by histology, prior lines of therapy and PD-L1 expression on tumour-infiltrating immune cells (IC), using an investigational immunohistochemistry (IHC) test that is being developed by Roche Diagnostics.

On September 27, 2015 Hospira Japan Co., Ltd. reported that the company has received an approval for the additional dosage/administration of gastric cancer for "Paclitaxel I.V. infusion [Hospira]" by a new drug application (NDA) based on evidence in the public domain with the Ministry of Health, Labour and Welfare (MHLW) in Japan (Press release, Hospira, SEP 27, 2015, View Source;p=RssLanding&cat=news&id=2090640 [SID:1234507569]).

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[Product name]
1. Paclitaxel I.V. lnfusion 30mg/5mL [Hospira]
2. Paclitaxel I.V. lnfusion 100mg/16.7mL [Hospira]

[Therapeutic Category]
Anticancer drug

[Dosage /administration for gastric cancer]
The underlined text represents the additional dosage/administration.

Method A or E are used for gastric cancer.
Method A: Normally for adults 210 mg/m2 (body surface area) in terms of Paclitaxel is administered over 3 hours in a single infusion, with intervals of at least three weeks between doses. This forms one course, which is repeated.
Method E: Normally for adults 80 mg/m2 (body surface area) in terms of paclitaxel is administered over 1 hour in a single infusion, once per week for three successive weeks, followed by an interval of at least two weeks. This forms one course, which is repeated.
Doses may be suitably reduced having regard to the condition of the patient.

On the basis of the requirement of the additional dosage/administration for gastric cancer for originator, which includes Paclitaxel, the report was prepared by the "Review Committee on Unapproved Drugs and Indications with High Medical Needs." The decision was made based on the report at the meeting of the Second Committee on New Drugs, Pharmaceutical Affairs and Food Sedation Council, held on March 5, 2015, which confirmed that filing through the "NDA based on evidence in the public domain" was reasonable for this additional dosage/administration.

The MHLW notification related to "NDA based on evidence in the public domain" for generics recommends pharmaceutical companies work on filing for additional dosage/administration for generic at the same time as originators. Hospira Japan filed this additional dosage/administration for "Paclitaxel I.V. infusion 30mg/5mL [Hospira] " and "Paclitaxel I.V. infusion 100mg/16.7mL [Hospira] " by "NDA based on evidence in the public domain."

Hospira Japan is committed to contributing to healthcare in Japan by providing value-added products with its broad portfolio and meeting the expectations of patients and healthcare professionals.