On May 16, 2018 MiNA Therapeutics, the pioneer in RNA activation therapeutics, reported that it will present preliminary results from its Phase I study of small activating RNA (saRNA) candidate MTL-CEBPA in liver cancer at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place in Chicago from June 1 – 5 (Press release, MiNA Therapeutics, MAY 16, 2018, View Source [SID1234526722]). The data will be featured in a Poster Discussion Session in the Developmental Therapeutics – Clinical Pharmacology and Experimental Therapeutics session. MiNA will announce the results through a press release following the presentation.

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Poster Discussion Session details:

Title: Preliminary results of a first-in-human, first-in-class phase I study of MTL-CEBPA, a small activating RNA (saRNA) targeting the transcription factor C/EBP-α in patients with advanced liver cancer
Abstract No: 2509
Session: Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics
Date / Time: June 4, 2018 at 3:00pm – 4:15pmLocation: S406

About MTL-CEBPA
MTL-CEBPA consists of a double stranded RNA formulated into a SMARTICLES liposomal nanoparticle and is designed to activate the CEBPA gene. By restoring CEBPA expression to normal levels, MTL-CEBPA has been demonstrated to attenuate or reverse liver disease in a range of pre-clinical studies including models of liver cancer, liver cirrhosis, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). MTL-CEBPA is currently under evaluation in OUTREACH, a first-in-human Phase I clinical study in patients with severe liver cancer. The multi-centre Phase I study is assessing the safety and tolerability of MTL-CEBPA in patients with advanced liver cancer who are ineligible or resistant to standard therapies. To learn more about the OUTREACH clinical study, please visit our listing at clinicaltrials.gov

On May 16, 2018 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported follow-up data from the phase III ALEX study, showing that, as an initial treatment, Alecensa (alectinib) significantly reduced the risk of disease progression or death (progression-free survival; PFS) by 57% (hazard ratio [HR]= 0.43, 95% CI: 0.32-0.58) compared to crizotinib after two years of follow-up in people with anaplastic lymphoma kinase (ALK)-positive metastatic (advanced) non-small cell lung cancer (NSCLC), as assessed by the investigator (Press release, Hoffmann-La Roche, MAY 16, 2018, View Source [SID1234526740]).1 The median PFS for people who received Alecensa was more than tripled compared to those who received crizotinib (34.8 months [95% CI: 17.7 months-NE) versus 10.9 months [95% CI: 9.1-12.9 months)], respectively, as assessed by the investigator. The safety profile for Alecensa was consistent with that observed in previous studies.

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"Follow-up results from the ALEX study demonstrate the significant sustained benefit of Alecensa, showing that people with metastatic ALK-positive non-small cell lung cancer lived for almost three years without their disease progressing," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "These results further support the use of Alecensa as a standard of care for people who are newly diagnosed with this form of lung cancer."

The longer-term analysis also included follow-up data for secondary endpoints of the ALEX study. Alecensa demonstrated superior efficacy compared to crizotinib regardless of the presence of central nervous system (CNS) metastases at baseline. Investigator-assessed median PFS for people without CNS metastases at baseline was 34.8 months with Alecensa (95% CI: 22.4-NE) versus 14.7 months (95% CI: 10.8-20.3) with crizotinib (HR=0.47, 95% CI: 0.32-0.71). Investigator-assessed median PFS for people with CNS metastases at baseline was 27.7 months in the Alecensa arm (95% CI: 9.2-NE) versus 7.4 months (95% CI: 6.6-9.6) in the crizotinib arm (HR=0.35, 95% CI: 0.22-0.56). 1 The duration of response (DOR) for people who received Alecensa was 33.3 months (95% CI: 31.3-NE) compared to 11.1 months (95% CI: 7.5-13.0 months) for people who received crizotinib.1

The data will be presented at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on Sunday, 3 June, 2018 at 08:00 – 11:30 am CDT (Abstract #9043).

Alecensa is now approved in more than 45 countries as an initial (first-line) treatment for ALK-positive, advanced NSCLC, including in the United States, Europe and Japan.

About the ALEX study2
ALEX (NCT02075840/B028984) is a randomised, multicentre, open-label, phase III study evaluating the efficacy and safety of Alecensa versus crizotinib in treatment-naïve people with ALK-positive NSCLC whose tumours were characterised as ALK-positive by the VENTANA ALK (D5F3) CDx Assay, a companion immunohistochemistry (IHC) test developed by Roche Tissue Diagnostics. People were randomised (1:1) to receive either Alecensa or crizotinib. The primary endpoint of the ALEX study was PFS as assessed by the investigator, and secondary endpoints include: Independent Review Committee (IRC)-assessed PFS, time to CNS progression, objective response rate (ORR), DOR and overall survival (OS). The multicentre study was conducted in 303 people across 161 sites in 31 countries. OS data are currently considered immature with only about a third of events being reported.

Primary data from the ALEX study were previously presented at the 2017 ASCO (Free ASCO Whitepaper) Annual Meeting and published in the New England Journal of Medicine.3 Follow-up results from the ALEX study analysis to be presented at the 2018 ASCO (Free ASCO Whitepaper) Annual Meeting showed1:

After a further 10 months of follow-up, Alecensa reduced the risk of disease worsening or death (PFS) by 57% compared to crizotinib (HR=0.43, 95% CI: 0.32-0.58). Median follow-up was 27.8 months versus 22.8 months for Alecensa-treated patients and crizotinib-treated patients, respectively.
Investigator-reported median PFS (the primary endpoint) was 34.8 months in the Alecensa arm (95% CI: 17.7-NE) versus 10.9 months (95% CI: 9.1-12.9 months) in the crizotinib arm.
ORR for people treated with Alecensa was 82.9% (95% CI: 75.95-88.51) compared to 75.5% (95% CI: 67.84-82.12) for people treated with crizotinib, as assessed by the investigator.
Alecensa demonstrated superior efficacy compared to crizotinib regardless of the presence or absence of CNS metastases at baseline. Investigator-assessed median PFS for people without CNS metastases at baseline was 34.8 months with Alecensa (95% CI: 22.4-NE) versus 14.7 months (95% CI: 10.8-20.3) with crizotinib (HR=0.47, 95% CI: 0.32-0.71). Investigator-reported median PFS for people with CNS metastases at baseline was 27.7 months in the Alecensa arm (95% CI: 9.2-NE) versus 7.4 months (95% CI: 6.6-9.6) in the crizotinib arm (HR=0.35, 95% CI: 0.22-0.56).
Improvements were observed in the time between first response to treatment and disease worsening (DOR): 33.3 months with Alecensa versus 11.1 months with crizotinib.
Grade 3-5 adverse events (AEs) were less frequent in the Alecensa arm (44.7%) compared to the crizotinib arm (51.0%). The most common Grade 3-4 AEs were increased liver enzymes (aspartate transaminase; 5.5%, and alanine transaminase; 4.6%) and increased muscle enzymes (creatine phosphokinase; 3.3%). Serious adverse reactions reported in ≥ 2% of people treated with Alecensa were acute kidney injury (2.6%) and decreased red blood cells (anaemia; 2.0%).
AEs leading to dose reduction (16.4% versus 20.5%) and dose interruption (22.4% versus 25.2%) were lower in the Alecensa arm compared with the crizotinib arm. AEs leading to discontinuation were equal in both arms (13.2%).
The FDA approval of Alecensa for the treatment of people with ALK-positive metastatic NSCLC was based on results from the phase III ALEX study from the primary data cutoff in February 2017. Results showed that:

Alecensa significantly reduced the risk of disease worsening or death (PFS) by 47% (HR=0.53, 95% CI: 0.38-0.73, p<0.001) compared to crizotinib as assessed by an IRC.
The median PFS was 25.7 months (95% CI: 19.9-NE) for people who received Alecensa compared with 10.4 months (95% CI: 7.7-14.6) for people who received crizotinib as assessed by an IRC.
Alecensa significantly reduced the risk of the cancer spreading to, or growing in, the brain or CNS compared to crizotinib by 84% (HR=0.16, 95% CI: 0.10-0.28, p<0.0001). This was based on a time to CNS progression analysis in which there was a lower risk of progression in the CNS as the first site of disease progression for people who received Alecensa (12%) compared to people who received crizotinib (45%).
The safety profile of Alecensa was consistent with that observed in previous studies.
Grade ≥ 3 adverse reactions were reported for 41% of people treated with Alecensa. The most common Grade 3-4 adverse reactions (≥ 3%) were evidence of kidney dysfunction (increased creatinine; 4.1%), evidence of liver dysfunction (hyperbilirubinemia; 5%), low levels of sodium (hyponatremia; 6%), increased liver enzymes (aspartate transaminase; 6%, and alanine transaminase; 6%), and decreased red blood cells (anaemia; 7%). Serious adverse reactions reported in ≥ 2% of people treated with Alecensa were pneumonia (4.6%) and renal impairment (3.9%).
About Alecensa
Alecensa (RG7853/AF-802/RO5424802/CH5424802) is a highly selective, CNS active, oral medicine created at Chugai Kamakura Research Laboratories and is being developed for people with NSCLC whose tumours are identified as ALK-positive. ALK-positive NSCLC is often found in younger people who have a light or non-smoking history.4 It is almost always found in people with a specific type of NSCLC called adenocarcinoma.4 Alecensa is now approved in over 45 countries as an initial (first-line) treatment for ALK-positive, metastatic NSCLC, including in the United States, Europe, Japan, Turkey, Cuba, Peru, Thailand, Australia, the Dominican Republic, India, Israel, Paraguay, Switzerland, Bolivia, Serbia, South Korea and Singapore. In addition, Alecensa is approved in the United States, Europe, Japan, Kuwait, Israel, Hong Kong, Canada, South Korea, Switzerland, India, Bolivia, Australia, Singapore, Taiwan, Thailand, Liechtenstein, Argentina, United Arab Emirates, Saudi Arabia, Peru, New Zealand, Cuba, the Dominican Republic, Qatar, Oman, Serbia, Paraguay and Turkey for the treatment of people with advanced (metastatic) ALK-positive NSCLC whose disease has worsened after, or who could not tolerate treatment with, crizotinib.

About Roche in lung cancer
Lung cancer is a major area of focus and investment for Roche, and we are committed to developing new approaches, medicines and tests that can help people with this deadly disease. Our goal is to provide an effective treatment option for every person diagnosed with lung cancer. We currently have four approved medicines to treat certain kinds of lung cancer and more than ten medicines being developed to target the most common genetic drivers of lung cancer or to boost the immune system to combat the disease.

On May 15, 2018 CASI Pharmaceuticals, Inc. (Nasdaq: CASI), a biopharmaceutical company dedicated to the development and delivery of high quality, cost-effective pharmaceutical products and innovative therapeutics to patients in the U.S., China and throughout the world, reported financial results for the first quarter and provided a review of recent accomplishments and anticipated upcoming milestones (Press release, CASI Pharmaceuticals, MAY 15, 2018, View Source [SID1234526614]).

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Ken K. Ren, Ph.D., CASI’s Chief Executive Officer, commented, "We have made significant progress in 2018, having acquired a portfolio of 25 US FDA-approved ANDAs from Sandoz, which has substantially broadened our product pipeline. The acquisition squarely enhances our strategic focus of capitalizing on the evolving CFDA landscape, which is expected to streamline and accelerate the approval process for high-quality generic products."

Dr. Ren continued, "The capital raise announced in March leaves us well-positioned to drive forward with our EVOMELA commercialization plans, and given the positive tenor of the April 2018 Center for Drug Evaluation (CDE) Expert Advisory Committee meeting, where no questions were posed and no new materials were requested, we remain encouraged that we will receive additional feedback from the CDE/CFDA regarding the EVOMELA application in the coming weeks. We remain committed to developing a strong and robust product portfolio through licensing opportunities as well as seeking other advantageous relationships that will further expand our footprint in both the U.S. and in China."

CASI Pharmaceuticals, Inc. / 9620 Medical Center Drive / Suite 300 / Rockville, MD 20850
Phone 240.864.2600 / Fax 301.315.2437

First Quarter and Recent Business Highlights

Company prepares for commercial launch of EVOMELA in China – In March 2018, CASI hired Thomas Zhang as General Manager of its Sales & Marketing team in China and is currently building out a robust and experienced team in China to support commercial operations there. Mr. Zhang has over 20 years of commercial experience in China, and prior to joining CASI was responsible for the successful launch and commercialization of Herceptin and Xeloda at Shanghai Roche Pharmaceuticals Co., Ltd. A team of seasoned sales and marketing professionals are being hired in preparation for the launch of EVOMELA following anticipated marketing authorization.

Update on advisory committee meeting notice from China Center for Drug Evaluation (CDE) – On April 26, 2018, the Center for Drug Evaluation (CDE), a group within the China FDA in charge of technical review, held a meeting of the Expert Advisory Anti-Tumor (Oncology) Drugs Committee (the "Advisory Committee") to review the EVOMELA application. In preparation for the Advisory Committee meeting, no additional questions were posed and the CDE requested no new analysis or materials. The Advisory Committee meeting did not include sponsor or public participants and the Advisory Committee will provide its recommendations directly to the CDE. CASI anticipates receiving feedback from the CDE/CFDA on the EVOMELA application in the coming weeks.

Acquired portfolio of 25 US FDA-approved ANDAs from Sandoz Inc. – In January 2018, the Company announced the acquisition of a portfolio of 25 US FDA-approved ANDAs, plus four pipeline ANDA’s that are pending FDA approval. CASI intends to select and commercialize certain products from the portfolio that have a unique market opportunity and cost-effective manufacturing in China and/or in the U.S.

Announced $50 million private placement to new and existing investors – In March 2018, the Company announced a $50 million private placement (common stock with accompanying warrants). Existing stockholders or their affiliates, including IDG-Accel China Growth Fund III, ETP Global Fund LP, and new stockholders including Robert W. Duggan, former Chairman and CEO of Pharmacyclics Inc., led the financing.

Upcoming presentations – CASI will provide a corporate update at the 2018 BIO International Convention (Boston, MA June 4-7).

Financial Results for the Quarter ended March 31, 2018

Cash Position: As of March 31, 2018, CASI had cash and cash equivalents of $49.9 million.

R&D Expenses: R&D expenses for the quarter ended March 31, 2018 were $1.7 million compared to $1.0 million in 2017, an increase of $0.7 million. The increase in R&D expenses primarily reflects costs associated with the technology transfer activities and regulatory support associated with the recently acquired ANDA portfolio, including non-cash intangible amortization expense of $0.3 million.

G&A Expenses: G&A expenses for the quarter ended March 31, 2018 were $1.3 million compared to $0.6 million in 2017. The increase in G&A over the prior year is primarily attributed to an increase in salary, benefits and recruitment expense in China, largely related to sales and marketing efforts to prepare for the anticipated launch of the Company’s first commercial product in China, as well as other general and administrative functions. There were also increased costs associated with business development, investor and public relations activities, and an increase in legal and other professional services fees during the 2018 period.

Net Loss: The Company reported a net loss of ($3.6 million), or ($0.05) per share, for the quarter ended March 31, 2018. This compares with a net loss of ($1.7 million), or ($0.03) per share for the first quarter of 2017. The increase in net loss is primarily due to costs associated the technology transfer activities and regulatory support for our ANDA portfolio, the write-off of approximately $0.7 million due to acquired in-process R&D primarily related to ANDAs not approved by the FDA, and increased costs associated with G&A functions, including employment costs for sales and marketing efforts, increased business development and investor relations activities, as well as other professional service fees.

On May 15, 2018 X4 Pharmaceuticals, a clinical stage biotechnology company developing novel CXCR4 antagonists to improve immune cell trafficking to treat cancer and rare disease, reported results from a pilot study of X4P-001-IO in combination with Opdivo (nivolumab) in patients with clear cell renal cell carcinoma (ccRCC) who are non-responsive to the anti-PD-1 checkpoint inhibitor Opdivo alone (Press release, X4 Pharmaceuticals, 15 15, 2018, View Source [SID1234526644]). The data were presented at the 16th Annual Meeting of the Association for Cancer Immunotherapy (CIMT) (Free CIMT Whitepaper), taking place May 15-17 in Mainz, Germany.

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Results from the nine patients with advanced ccRCC enrolled in the pilot study as of February 26, 2018 were presented at the CIMT (Free CIMT Whitepaper) meeting in a poster session on May 15th and an oral presentation on May 17th. All patients in the study were non-responsive to single agent Opdivo with either stable or progressive disease. Enrolled patients continued to receive standard bi-weekly Opdivo therapy and X4P-001-IO (400 mg, oral, once daily). Median duration of treatment with the combination was 3.7 months (range 1-10 months).

Highlights of the data presented at CIMT (Free CIMT Whitepaper) include:

X4P-001-IO in combination with Opdivo had acceptable toxicity. The most frequent adverse events were diarrhea, nasal congestion, dry eye, headache and cough. No grade 4 or 5 adverse events occurred. All Grade 3/serious adverse events were manageable with appropriate intervention.
Combination therapy with X4P-001-IO and Opdivo exhibited anti-tumor activity in some patients with advanced ccRCC who were previously non-responsive to single agent Opdivo therapy.
Four patients who had progressed on prior Opdivo monotherapy had a best response of stable disease with additional X4P-001-IO treatment.
Of the five patients who were stable on prior Opdivo monotherapy, one had a partial response with combination therapy.
"These data demonstrate that the combination with X4P-001-IO and nivolumab has the potential to augment responses in patients who previously received the anti-PD-1 checkpoint inhibitor nivolumab alone," said David F. McDermott, M.D., Beth Israel Deaconess Medical Center, Harvard Medical School and lead investigator of the study. "This preliminary data requires validation in larger studies as we continue to seek treatments to address the larger population of cancer patients who do not adequately respond to checkpoint inhibitors."

"These findings contribute to our growing understanding of combining CXCR4 antagonists with other agents such as checkpoint inhibitors," said Sudha Parasuraman, M.D., Chief Medical Officer of X4 Pharmaceuticals. "Because the mechanisms of CXCR4 antagonism and check point inhibition act at different points in the tumor immunity cycle, it is reasonable to consider the potential for synergistic activity."

About X4P-001-IO in Cancer

X4P-001-IO is an investigational selective, oral, small molecule antagonist of C-X-C receptor type 4 (CXCR4). CXCR4 is a chemokine receptor present in abundance on certain immune cells and cancer cells and it plays a critical role in immune cell trafficking, infiltration and activation in the tumor microenvironment. CXCR4 signaling is disrupted in a broad range of cancers, facilitating tumor growth by allowing cancer cells to evade immune detection and creating a pro-tumor microenvironment. X4P-001-IO has the ability to help restore immunity within the tumor microenvironment and has the potential to enhance the anti-tumor activity of approved and emerging oncology agents, such as checkpoint inhibitors and targeted therapies. X4P-001-IO is being investigated in several clinical studies in solid tumors.

On May 15, 2018 Cleveland BioLabs, Inc. (NASDAQ:CBLI) reported financial results and development progress for the first quarter ended March 31, 2018 (Press release, Cleveland BioLabs, MAY 15, 2018, View Source [SID1234526615]).

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Cleveland BioLabs reported a net loss of $(1.2) million, excluding minority interests, for the first quarter of 2018, or $(0.11) per share, compared to a net loss, excluding minority interests, of $(1.7) million, or $(0.15) per share, for the same period in 2017. The decrease in net loss was primarily due to a non-cash adjustment to our warrant liabilities and reduced operating costs partially offset by reduced revenue.

As of March 31, 2018, the Company had $7.7 million in cash, cash equivalents and short-term investments, which, based on the Company’s current operational plan, is estimated to fund operations for at least one year beyond the filing date of our Form 10-Q.

Yakov Kogan, Ph.D., MBA, Chief Executive Officer, stated, "The past quarter was one of important progress for the company and our Entolimod program. We continued our pursuit of a pre- Emergency Use Authorization ("pre-EUA") with the U.S. Food and Drug Administration ("FDA") and a Marketing Authorization Application ("MAA") with the European Medicines Agency ("EMA") for entolimod as a medical radiation countermeasure."

"As previously reported, the company has received Day 120 review questions from EMA regarding the MAA for entolimod and a formal notification that responses to these questions should be submitted to the agency by September 14, 2018. Consistent with the FDA review of the company’s pre-EUA application, several of the EMA review questions focused on the comparability between the entolimod formulation used in prior safety and efficacy studies and the formulation proposed for commercialization. The analytical analysis of the specimens collected during an in-vivo biocomparability study in non-human primates to address these comparability questions is ongoing," added Dr. Kogan. "Other Day 120 questions from the EMA are generally similar to those discussed in the past with the FDA, and include questions on validation of various aspects of manufacturing, the animal-to-human dose-conversion strategy, and the human safety database."

Further Financial Results

Revenue for the first quarter of 2018 decreased to $0.2 million compared to $0.6 million for the first quarter of 2017. The decrease was primarily due to decreased revenue from our Joint Warfighter Medical Research Program contract from the Department of Defense for the continued development of the entolimod as a medical radiation countermeasure.

Research and development costs for the first quarter of 2018 decreased to $1.3 million compared to $1.4 million for the first quarter of 2017. The reduction in research and development costs is primarily due to reductions in entolimod for biodefense applications partially offset by increases in the entolimod family of compounds for oncology.

General and administrative costs for the first quarter of 2018 decreased to $0.7 million compared to $0.8 million for the first quarter of 2017. This decrease was primarily attributable to reductions in personnel and other operating costs in connection with cost savings efforts to streamline operations.