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FDA approves Roche’s Tecentriq in combination with chemotherapy for the initial treatment of adults with extensive-stage small cell lung cancer

On March 19, 2019 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the U.S. Food and Drug Administration (FDA) approved Tecentriq (atezolizumab), in combination with carboplatin and etoposide (chemotherapy), for the initial (first-line) treatment of adults with extensive-stage small cell lung cancer (ES-SCLC) (Press release, Hoffmann-La Roche, MAR 19, 2019, View Source [SID1234534499]). This approval is based on results from the Phase III IMpower133 study, which showed that Tecentriq in combination with chemotherapy helped people live significantly longer compared to chemotherapy alone (median overall survival [OS]=12.3 vs. 10.3 months; hazard ratio [HR]=0.70, 95% CI: 0.54–0.91; p=0.0069) in the intention-to-treat (ITT) population.[1] The Tecentriq-based combination also significantly reduced the risk of disease worsening or death (progression-free survival, PFS) compared to chemotherapy alone (PFS=5.2 versus 4.3 months; HR=0.77, 95% CI: 0.62-0.96; p=0.017). Safety for the Tecentriq and chemotherapy combination appeared consistent with the known safety profile of Tecentriq.

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"Tecentriq is the first cancer immunotherapy approved for the initial treatment of extensive-stage small cell lung cancer, which is especially difficult to treat," said Sandra Horning, M.D., Roche’s Chief Medical Officer and Head of Global Product Development. "Until now, there have been limited treatment advances for this disease, and we are excited to bring a potential new standard of care to patients that has been shown to improve survival compared to chemotherapy.

Results from the Phase III IMpower133 study were simultaneously presented at the 2018 World Conference on Lung Cancer (WCLC) and published in The New England Journal of Medicine.

In the US, Tecentriq is approved in combination with Avastin (bevacizumab), paclitaxel and carboplatin (chemotherapy), for the initial (first-line) treatment of adults with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumour aberrations. In Europe, the Tecentriq and Avastin combination is approved for the initial treatment of people with metastatic non-squamous NSCLC, including people with EGFR mutant or ALK genomic tumour aberrations after failure of appropriate targeted therapies. Tecentriq is also approved by the FDA to treat adults with metastatic NSCLC who have disease progression during or following platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumour aberrations should have disease progression on FDA approved therapy for NSCLC harbouring these aberrations prior to receiving Tecentriq.

About the IMpower133 study
IMpower133 is a Phase III, multicentre, double-blinded, randomised placebo-controlled study evaluating the efficacy and safety of Tecentriq in combination with chemotherapy (carboplatin and etoposide) vs. chemotherapy (carboplatin and etoposide) alone in chemotherapy-naïve adults with ES-SCLC.

The study enrolled 403 people who were randomised equally (1:1) to receive:

Tecentriq in combination with carboplatin and etoposide (Arm A), or
Placebo in combination with carboplatin and etoposide (Arm B, control arm)
During the treatment-induction phase, people received treatment on 21-day cycles for four cycles, followed by maintenance with Tecentriq or placebo until progressive disease (PD) as assessed by the investigator using Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1). Treatment could be continued until persistent radiographic PD or symptomatic deterioration was observed.

The co-primary endpoints were progression-free survival (PFS) as determined by the investigator using RECIST v1.1 and OS in the ITT population.

A summary of the ITT data from the IMpower133 study that support this approval is included below.[1]

Tecentriq in combination with chemotherapy helped people live significantly longer compared to chemotherapy alone (OS=12.3 vs. 10.3 months; HR=0.70, 95% CI: 0.54-0.91; p=0.0069) in the ITT population.
The Tecentriq-based combination also significantly reduced the risk of disease worsening or death compared to chemotherapy alone (PFS=5.2 vs. 4.3 months; HR=0.77; 95% CI: 0.62-0.96; p=0.017).
Safety for the Tecentriq and chemotherapy combination appeared consistent with the known safety profile of Tecentriq. Serious adverse reactions occurred in 37% of people receiving Tecentriq plus chemotherapy compared to 35% of people receiving chemotherapy alone. The most common adverse reactions (≥20%) in people receiving Tecentriq plus chemotherapy were feeling tired or weak (fatigue/asthenia; 39%), nausea (38%), hair loss (alopecia; 37%), decreased appetite (27%) and constipation (26%) and vomiting (20%).
About SCLC
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 SCLC, with SCLC accounting for approximately 15% of all lung cancer cases.[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 nine Phase III lung cancer studies evaluating Tecentriq alone or in combination with other medicines.

In the United States Tecentriq in combination with nab-paclitaxel is approved for treatment of PD-L1-positive metastatic triple-negative breast cancer; and in combination with Avastin and chemotherapy for the initial treatment of people with metastatic non-squamous NSCLC. In the Europe Union, the non-squamous NSCLC indication includes people with EGFR mutant or ALK genomic tumour aberrations after failure of appropriate targeted therapies. Tecentriq is also approved in the European Union, United States and more than 85 countries for people with previously treated metastatic non-small cell lung cancer (NSCLC) and for certain types of untreated or previously treated metastatic urothelial carcinoma who are not eligible for cisplatin chemotherapy, or who have had disease progression during or following platinum-containing therapy.

About Roche in cancer immunotherapy
For more than 50 years, Roche has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever in our effort to bring innovative treatment options that help a person’s own immune system fight cancer. By applying our seminal research in immune tumour profiling within the framework of the Roche-devised cancer immunity cycle, we are accelerating and expanding the transformative benefits with Tecentriq to a greater number of people living with cancer. Our cancer immunotherapy development programme takes a comprehensive approach in pursuing the goal of restoring cancer immunity to improve outcomes for patients.

To learn more about the Roche approach to cancer immunotherapy please follow this link: View Source

Nurix Therapeutics to Present at 2019 American Association for Cancer Research (AACR) Annual Meeting

On March 19, 2019 Nurix Therapeutics, Inc., a private company discovering drugs that harness the body’s natural process to control protein levels, reported an upcoming oral presentation at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting from March 29 – April 3, 2019 at the Georgia World Conference Center in Atlanta, Georgia (Press release, Nurix Therapeutics, MAR 19, 2019, View Source [SID1234534497]).

ORAL PRESENTATION DETAILS
Presentation Title: Genetic and pharmacologic evaluation of the ubiquitin ligase CBL-B as a small-molecule, tumor immunotherapy target
Session Category: Experimental and Molecular Therapeutics
Session Title: Preclinical Drug Development
Date: Monday, April 1, 2019
Time: 3:50 p.m.-4:05 p.m. EDT
Location: Georgia World Conference Center, Room B206

FDA Grants Exemption to Import Alert for Cellectar’s CLR 131 in Pediatric and Adolescent Patients

On March 19, 2019 Cellectar Biosciences, Inc. (NASDAQ: CLRB), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of drugs for the treatment of cancer, reported that the U.S. Food and Drug Administration (FDA) has granted an exemption to the Import Alert placed on the Centre for Probe Development and Commercialization (CPDC) for the use of CLR 131 in connection with the company’s pediatric IND (Press release, Cellectar Biosciences, MAR 19, 2019, View Source [SID1234534493]). This exemption will allow Cellectar to immediately begin enrolling patients in its Phase 1 pediatric study for the treatment of select relapsed or refractory solid tumors including neuroblastoma, lymphomas and malignant brain tumors.

Cellectar is already enrolling patients in its Phase 1 and Phase 2 multiple myeloma and select B-cell lymphoma studies of CLR 131 after having received FDA exemption to the CPDC Import Alert in November 2018 for its hematology IND.

"We are grateful that the FDA has granted this additional exemption for CLR 131, which allows us to immediately initiate our pediatric clinical study in children battling life-threatening cancers," said James Caruso, president and CEO of Cellectar. "These patients have a very poor prognosis and low rates of survival as a result of limited effective treatment options. Based on our preclinical and ongoing clinical studies, we are optimistic that CLR 131 has the potential to provide a meaningful treatment option for children suffering from cancers with high unmet medical needs."

About the Phase 1 Pediatric Study of CLR 131

The Phase 1 pediatric study will be an open-label, sequential-group, dose-escalation study to evaluate the safety and tolerability of a single intravenous administration of CLR 131 in up to 30 children and adolescents with cancers, including neuroblastoma, sarcomas, lymphomas (including Hodgkin’s lymphoma) and malignant brain tumors. Secondary objectives of the study are to identify the recommended Phase 2 dose of CLR 131 and to determine preliminary antitumor activity (treatment response) of CLR 131 in children and adolescents. We plan to initiate this Phase 1 study at 5-7 pediatric cancer centers, within and possibly outside the US.

About CLR 131

CLR 131 is a small-molecule, cancer-targeting radiotherapeutic PDC designed to deliver cytotoxic radiation directly and selectively to cancer cells and cancer stem cells. CLR 131 is our lead therapeutic PDC product candidate and is currently being evaluated in both Phase 2 and Phase 1 clinical studies. In December 2014, the FDA granted orphan drug designation for CLR 131 for the treatment of multiple myeloma. In 2018, the FDA granted orphan drug and rare pediatric disease designations for CLR 131 for the treatment of neuroblastoma, rhabdomyosarcoma, Ewing’s sarcoma and osteosarcoma. The FDA previously accepted our IND application for a Phase 1 open-label, dose-escalating study to evaluate the safety and tolerability of a single intravenous administration of CLR 131 in up to 30 children and adolescents with cancers including neuroblastoma, sarcomas, lymphomas (including Hodgkin’s lymphoma) and malignant brain tumors

DiaMedica Therapeutics Announces 2018 Financial Results and Provides Corporate Update

On March 19, 2019 DiaMedica Therapeutics Inc. (Nasdaq: DMAC), a clinical-stage biopharmaceutical company focused on developing novel treatments for kidney diseases and neurological disorders, reported its financial results for the year ended December 31, 2018 (Press release, DiaMedica, MAR 19, 2019, View Source [SID1234534492]).

Business Highlights

"In the past year, DiaMedica has achieved important development goals for our two lead programs, DM199 for chronic kidney disease and acute ischemic stroke. We expect to build upon this success in 2019 as we work toward advancing our pipeline of clinical programs, which hold the potential to have significant impact on patients suffering from chronic kidney disease and acute ischemic stroke," stated Rick Pauls, DiaMedica’s President and CEO. "After our successful Nasdaq IPO in December, we have sufficient capital to obtain Phase II read-outs in our two lead programs. We are well positioned to execute on our clinical development plans to achieve meaningful milestones in the next year, and we look forward to sharing our progress."

U.S. IPO, Nasdaq Uplisting and U.S. Reporting Company

On December 6, 2018, DiaMedica completed an initial public offering ("IPO") of its common shares in the United States and uplisted to the Nasdaq Capital Market, raising $16.4 million in gross proceeds and $14.7 million in net proceeds. This was an important milestone for DiaMedica that expanded its investor base, adding several U.S. institutional investors, and strengthened its balance sheet. The IPO also provided the capital to complete Phase II clinical trials for DM199 in patients suffering acute ischemic strokes ("AIS") and chronic kidney disease ("CKD").

License of DM199 with Ahon Pharma, subsidiary of Fosun Pharma.

In September 2018, DiaMedica signed a license and collaboration agreement with Fosun Pharma’s Ahon Pharma subsidiary for acute ischemic stroke in China. Fosun is one of the largest Chinese pharmaceutical firms with an extensive hospital sales force. The agreement provides exclusive rights to clinically develop and commercialize DM199 solely for acute ischemic stroke in China, Taiwan, Hong Kong and Macau. Under the terms of the agreement, DiaMedica may receive approximately $32 million in milestone payments, plus sales-based royalties of up to approximately 10%. In addition, DiaMedica has retained full control over the manufacturing of DM199. Ahon Pharma is currently preparing an application for an investigational new drug application to the China National Medical Products Administration. In China, a form of the KLK1 protein extracted from human urine, known as u-KLK1 or Kailikang, has been approved and is considered a standard of care for AIS patients.

Clinical Developments

DM199 for the Treatment of Chronic Kidney Disease

Enrolling Patients in Phase Ib Clinical Study in Patients with CKD

In December 2018, the United States Food & Drug Administration ("FDA") accepted DiaMedica’s investigational new drug ("IND") application to study DM199 in patients with CKD. In February 2019, the Company began enrolling patients in its Phase Ib clinical study, which is being conducted at 3 sites in the U.S. and all sites are actively enrolling patients. The open label clinical trial is evaluating three dose levels of DM199, administered in a single subcutaneous ("SC") dose, in 32 patients with moderate or severe CKD. Primary endpoints include safety, tolerability, pharmacokinetics, change in KLK1 levels, albumin to creatine ratios and kidney biomarkers measured over a 12-day period. This study is intended to assist in identifying dose levels for use in subsequent Phase II trials. The Company expects a readout on the results of the CKD study in mid-2019.

Released Chronic Kidney Disease White Paper

Today, DiaMedica also released a white paper that further details the potential of KLK1/DM199 to treat patients with chronic kidney disease. The paper can be accessed at www.diamedica.com/product-candidates/chronic-kidney-disease.

DiaMedica is currently planning a randomized Phase II study in patients with rare forms of chronic kidney disease to be initiated in the second half of 2019. The Company will have updates on the rare forms to be targeted in this study and other details to follow.

DM199 for the Treatment of Acute Ischemic Stroke

DM199 Acute Ischemic Stroke Phase II "REMEDY" Trial Update.

In 2018, the Company initiated treatment of patients in its Phase II randomized, double-blind, placebo-controlled multi-center evaluation to assess the safety, tolerability and markers of DM199 in acute ischemic stroke patients, the REMEDY trial. With the success of its IPO, DiaMedica raised its target enrollment in the REMEDY trial from 60 to approximately 100 patients to provide additional data to support the design of a robust and efficient Phase III study. In this trial, the study drug (DM199 or placebo) is administered as an intravenous ("IV") infusion within 24 hours of stroke symptom onset, followed by SC injections later that day and once every 3 days for 21 days (8 SC doses). Multiple plasma-based biomarkers (e.g. C-reactive protein), the Modified Rankin Scale, National Institutes of Health Stroke Scale and the Barthel Index will be assessed at multiple points throughout the study, including 90 days post-stroke. This study will also include multiple tests to investigate DM199’s therapeutic potential. With the increase in the enrollment target, the Company expects to complete this trial in the fourth quarter of 2019 or first quarter of 2020.

AIS Review Paper Supporting the Use of DM199 for AIS Published in Peer-Reviewed Journal

On January 22, 2019, DiaMedica announced that a manuscript titled "Human Tissue Kallikrein in the Treatment of Acute Ischemic Stroke" was published in the peer-reviewed medical journal "Therapeutic Advances in Neurological Disorders (TAND)." The paper reviews the scientific literature covering the biochemical role of KLK1 and presents the mechanistic rationale for using KLK1 as an additional pharmacological treatment for AIS. In addition to the biochemical mechanism of KLK1, the paper highlights supporting results from human genetics and preclinical animal models of brain ischemia. It also reviews published clinical results for treatment of AIS by a form of KLK1 that is isolated from human urine. This form has been approved for post-infarct treatment of AIS in China and data has been published on clinical trials involving over 4,000 patients. The paper offers a series of testable therapeutic hypotheses for demonstrating the long-term beneficial effect of KLK1 treatment in AIS patients and the reasons for this action.

Financial Results

License revenue for 2018 was comprised of the initial $500,000 license payment DiaMedica received in connection with the license and collaboration agreement with Ahon Pharma.

Research and development expenses were $4.5 million for the year ended December 31, 2018 compared to $3.2 million for the year ended December 31, 2017, an increase of $1.3 million. The increase was primarily due to the additional preclinical testing and related costs required to support an application for an investigational new drug application in the United States, higher study costs for the REMEDY Phase II stroke study as compared with the DM199 bridging study which was substantially completed in 2017, and increased personnel and non-cash stock-based compensation costs.

General and administrative expenses were $2.7 million for the year ended December 31, 2018 compared to $1.3 million for the year ended December 31, 2017. General and administrative costs increased due to one-time costs incurred associated with the Company’s planned IPO in the United States, primarily the Nasdaq listing process and related legal and accounting fees. Higher salaries, fees and short-term benefits due to the addition of staff and higher share-based compensation also contributed to the increase during 2018.

Other income, net, was $1.1 million for the year ended December 31, 2018 compared to $259,000 for 2017. The increase resulted primarily from the recognition of the research and development incentive from the Australia Government paid for qualifying research work performed by DiaMedica Australia. This increase was partially offset by increased foreign currency transaction losses.

Balance Sheet and Cash Flow

Total cash resources were $16.8 million as of December 31, 2018, compared to $1.4 million as of December 31, 2017. Total current assets were $18.0 million and $1.5 million as of December 31, 2018 and December 31, 2017, respectively. These increases resulted primarily from net proceeds of $20.6 million received from the sale of common shares and warrants during 2018, partially offset by the use of cash to fund operations in the current year,

Current liabilities increased to $1.3 million as of December 31, 2018, compared to $1.0 million as of December 31, 2017. The increase in current liabilities resulted primarily from the increase in costs accrued related to clinical trials.

Net cash used in operating activities was $5.7 million for the year ended December 31, 2018, up from $3.9 million for the year ended December 31, 2017. The net cash used in each of these periods primarily reflects the net loss for these periods, and was partially offset by non-cash charges for stock-based compensation and the net effects of changes in operating assets and liabilities.

Conference Call Information

DiaMedica management will host a conference call to discuss these results on Wednesday March 20, 2019, at 8:00 a.m. Central Time:

Date:

Wednesday, March 20, 2019

Time:

8:00 AM CT

Web access:

View Source

Dial In:

(866) 962-3583 (domestic)

(630) 652-5857 (international)

Conference ID:

6773627

Listeners should log on to the website or dial in 15 minutes prior to the call. The webcast will remain available for play back on our website, under investor events and presentations, following the earnings call and for 12 months thereafter. A telephonic replay of the conference call will be available until March 28, 2019, by dialing 1(855) 859-2056 (US Toll Free Dial In), (404) 537-3406 (international), replay passcode 6773627.

About DM199

DM199 is a recombinant (synthetic) form of the human serine protease, KLK1. The KLK1 protein plays an important role in the regulation of diverse physiological processes including blood flow, inflammation, fibrosis, oxidative stress and neurogenesis via a molecular mechanism that increases production of nitric oxide and prostacyclin. KLK1 deficiency may play a role in multiple vascular and fibrotic diseases such as chronic kidney disease, retinopathy, stroke, vascular dementia, and resistant hypertension where current treatment options are limited or ineffective. DiaMedica is the first company to have developed a recombinant form of the KLK1 protein. The KLK1 protein, produced from porcine pancreas and human urine, has been used to treat patients in Japan, China and Korea for decades. DM199 is currently being studied in patients with acute ischemic stroke and patients with chronic kidney disease.

Context to Participate in Upcoming Investor Conferences in April

On March 19, 2019 Context Therapeutics, a clinical-stage biotechnology company focused on hormone driven cancers, reported it will present at the following upcoming investor conferences (Press release, Context Therapeutics, MAR 19, 2019, View Source [SID1234534482]).

Needham and Company 18th Annual Health Care Conference in New York City on Tuesday, April 9, 2019 at 2:30 p.m. ET.