On August 6, 2019 Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE:CFBI), a biotechnology company with a pipeline of proprietary small molecule drugs that address cancer, liver and inflammatory diseases, reported that a supply of Namodenoson has been manufactured and is ready for use in the treatment of advanced liver cancer patients under compassionate use at the Rabin Medical Center in Israel (Press release, Can-Fite BioPharma, AUG 6, 2019, View Source [SID1234538211]).

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Compassionate use allows doctors and their patients the option of early access to investigational new drugs, under closely controlled and monitored circumstances, when a patient who is facing serious illness has exhausted all available treatment options.

Salomon M. Stemmer, MD, the Principal Investigator of the Company’s prior Phase II liver cancer study said, "Given the evidence of clinical benefit of Namodenoson in patients with hepatocellular carcinoma and Child Pugh B7 to whom there is no accepted well established treatment, I plan to offer Namodenoson to certain HCC CPB7 patients in the compassionate use setting."

Can-Fite recently announced results from its Phase II study of Namodenoson in the treatment of advanced liver cancer. Namodenoson was found to increase overall survival in HCC patients with Child Pugh B7, the largest subpopulation of the study, as compared to placebo, even though the trial did not meet its primary endpoint.

An end of Phase II meeting with the U.S. Food and Drug Administration to review study data and to present the design of a Phase III clinical trial is expected soon. The FDA has granted Namodenoson both Orphan Drug and Fast Track status providing a pathway for accelerated approval based on unmet need in the treatment of advanced liver cancer. Fast Track designation offers advantages including more frequent meetings with the FDA and rolling review, which provides the opportunity to submit parts of its New Drug Application (NDA) for review prior to completing the entire application for commercialization. Orphan Drug designation includes 7-year market exclusivity following marketing approval, FDA assistance during the drug development process, and exemption of application fees.

About Namodenoson

Namodenoson is a small orally bioavailable drug that binds with high affinity and selectivity to the A3 adenosine receptor (A3AR). Namodenoson is being evaluated in Phase II trials for two indications, as a second line treatment for hepatocellular carcinoma, and as a treatment for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). A3AR is highly expressed in diseased cells whereas low expression is found in normal cells. This differential effect accounts for the excellent safety profile of the drug.

On August 6, 2019 CytoSorbents Corporation (NASDAQ: CTSO), a critical care immunotherapy leader using its CytoSorb blood purification technology to treat deadly inflammation in critically-ill and cardiac surgery patients around the world, reported financial and operational results for the quarter ending June 30, 2019 (Press release, Cytosorbents, AUG 6, 2019, View Source [SID1234538227]).

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Second Quarter 2019 Financial Results:

Total Q2 2019 revenues were $6.2 million, including both product sales and grant income, an increase of approximately 8% from $5.8 million in Q2 2018
Product sales for Q2 2019 were approximately $5.9 million, compared to $5.2 million for Q2 2018, an increase of approximately 12%. Q2 2019 product sales would have been approximately $6.2 million, or $357,000(18%) higher than a year ago, had the Euro remained unchanged
Product gross margins for Q2 2019 increased to 76%, compared to 74% in Q2 2018
Executed a loan amendment with Bridge Bank which provided an additional $5 million in debt financing which was received on July 31, 2019, extending the interest-only period of the entire term loan to October 2020, provided certain financial targets are met
Strong cash position with $16.3M at the end of the quarter, and approximately $20 million at the end of July, reflecting the additional proceeds from debt
Second Quarter 2019 Operational Highlights:

67,000+ cumulative CytoSorb treatments have been delivered, up from 46,000 a year ago
CytoSorb product registration has been submitted in Mexico and South Korea with partner Fresenius Medical Care, with concurrent initiation of commercialization planning and pre-launch activities including conferences, marketing, and key opinion leader events. Feedback on the status of registration is expected before the end of this year
Publication of the U.S. REFRESH I study in Seminars in Thoracic and Cardiovascular Surgery, a journal of the American Association for Thoracic Surgery (AATS) and an associated editorial commentary on the clinical trial and the potential clinical importance and value that CytoSorb could have in complex cardiac surgery with future studies
Enrollment in the 400 patient U.S. REFRESH 2-AKI pivotal randomized, controlled trial is currently at 109 patients with 24 active sites
The German government-funded REMOVE endocarditis trial is approximately 90% enrolled, with 222 patients out of a target 250 patients at 15 clinical sites. Completed enrollment is expected by year-end
The HemoDefend-RBC program remains on track for an investigational device exemption (IDE) submission to the FDA this year, enabling the start of the U.S. pivotal trial
Dr. Phillip Chan, Chief Executive Officer of CytoSorbents Corporation, stated, "Q2 2019 product sales rebounded significantly over the past quarter, achieving our guidance as the best quarter of product sales since we began commercialization, and in-line with our historical product sales trajectory of growth. Results were aided by the resumption of ordering from one of our major distributors. We also attained blended product gross margins of 76%, an increase of 200 basis points from the prior quarter, primarily resulting from continued efficiencies in manufacturing, and closing in on our goal of 80% on a quarterly basis this year."

"The new loan amendment with Bridge Bank has expanded our effective working capital position by approximately $9 million, including deferment of principal repayments, and will allow us to continue making the investments in our business that will drive future growth. We expect that product sales in the second half of this year will solidly exceed product sales in the first half, catalyzed by the impact of our expanding sales team, organic growth in existing markets, increased international expansion, publication of new clinical data in a wide variety of clinical applications, and increased partner support."

Dr. Chan concluded, "Lastly, in the independent editorial commentary to the REFRESH I paper that was recently published, we were pleased to note that the authors described the complications of extended cardiopulmonary bypass – including the activation of inflammation, release of free hemoglobin due to hemolysis, and organ injury and failure – as the ‘Achilles heel of complex cardiac surgery’, and that the ‘holy grail of research in this subject would be to find something able to mitigate or eliminate the mediators responsible for these potentially catastrophic downstream effects of prolonged cardiopulmonary bypass.’ In reality, CytoSorb has demonstrated utility in so many different life-or-death applications in critical care and cardiac surgery, that we believe we are one of the leading innovators in bringing game-changing advances to medicine."

"Please join us on our earnings conference call today, details for which are below."

Conference Call Details:
Date: Tuesday, August 6, 2019
Time: 4:45 PM Eastern Time
Participant Dial-In: 877-451-6152
Conference ID: 13692360
Live Presentation Webcast: View Source

It is recommended that participants dial in approximately 10 minutes prior to the start of the call. There will also be a simultaneous live webcast of the conference call that can be accessed through the following audio feed link: View Source

An archived recording of the conference call will be available under the Investor Relations section of the Company’s website at View Source

Results of Operations

Comparison for the three months ended June 30, 2019 and 2018:

Revenues:

Revenue from product sales was approximately $5,850,000 in the three months ended June 30, 2019, as compared to approximately $5,246,000 in the three months ended June 30, 2018, an increase of approximately $604,000, or 12%. This increase was driven by an increase in direct sales of approximately $520,000 resulting from sales to both new customers and repeat orders from existing customers and an increase in distributor sales of approximately $84,000. In addition, sales were negatively impacted by approximately $357,000 as a result of the decrease in the average exchange rate of the Euro to the U.S. dollar. For the three months ended June 30, 2019, the average exchange rate of the Euro to the U.S. dollar was $1.12 as compared to an average exchange rate of $1.19 for the three months ended June 30, 2018.

Grant income was approximately $382,000 for the three months ended June 30, 2019 as compared to approximately $510,000 for the three months ended June 30, 2018, a decrease of approximately $128,000 or 25%. This decrease was a result of timing of certain grant revenue.

Total revenues were approximately $6,233,000 for the three months ended June 30, 2019, as compared to total revenues of approximately $5,755,000 for the three months ended June 30, 2018, an increase of approximately $478,000, or 8%.

Cost of Revenues:

For the three months ended June 30, 2019 and 2018, cost of revenue was approximately $1,834,000 and $1,786,000, respectively, an increase of approximately $48,000. Product cost of revenues increased approximately $31,000 during the three months ended June 30, 2019 as compared to the three months ended June 30, 2018 due to increased sales. Product gross margins were approximately 76% for the three months ended June 30, 2019 and approximately 74% for the three months ended June 30, 2018.

Research and Development Expenses:

For the three months ended June 30, 2019, research and development expenses were approximately $2,930,000 as compared to research and development expenses of approximately $1,576,000 for the three months ended June 30, 2018. The increase of approximately $1,354,000 was due to an increase in clinical trial costs of approximately $1,215,000, which is primarily related to our REFRESH 2-AKI trial, an increase in non-clinical research and development salary related costs of approximately $11,000 and an increase in other non-clinical research and development costs of approximately $150,000. These increases were offset by an increase in direct labor and other costs being deployed toward grant-funded activities of approximately $18,000, which had the effect of decreasing the amount of our non-reimbursable research and development costs, and a decrease in new product development costs of approximately $4,000.

Legal, Financial and Other Consulting Expense:

Legal, financial and other consulting expenses were approximately $592,000 for the three months ended June 30, 2019, as compared to approximately $458,000 for the three months ended June 30, 2018. The increase of approximately $134,000 was due to an increase in legal fees of approximately $28,000 related to patent matters and certain corporate initiatives, an increase in consulting fees of approximately $55,000, an increase in employment agency fees of approximately $31,000 and an increase in accounting fees of approximately $20,000.

Selling, General and Administrative Expense:

Selling, general and administrative expenses were approximately $4,507,000 for the three months ended June 30, 2019, as compared to approximately $6,124,000 for the three months ending June 30, 2018, a decrease of $1,617,000. The decrease of $1,617,000 was due to a decrease in non-cash stock compensation of approximately $2,228,000, a decrease in travel and entertainment costs of approximately $64,000 and a decrease in other general and administrative expenses of approximately $70,000. These decreases were offset by an increase in salaries, commissions and related costs of approximately $588,000, additional sales and marketing costs, which include advertising and conferences of approximately $92,000, an increase in royalty expenses of approximately $53,000 due to the increase in product sales and an increase in rent expense of approximately $12,000 related to the expansion of manufacturing and office facilities.

Interest Expense, net:

For the three months ended June 30, 2019, interest expense was approximately $215,000, as compared to interest expense of approximately $840,000 for the three months ended June 30, 2018. This decrease in interest expense of approximately $625,000 was primarily a result of the settlement of the Success Fee with Bridge Bank in the amount of $637,000 that became due in May 2018 in accordance with the terms of the 2016 Success Fee Letter with Bridge Bank.

Gain (Loss) on Foreign Currency Transactions:

For the three months ended June 30, 2019, the gain on foreign currency transactions was approximately $297,000 as compared to a loss of approximately $(794,000) for the three months ended June 30, 2018. The 2019 gain was directly related to the increase in the spot exchange rate of the Euro to the U.S. dollar at June 30, 2019 as compared to March 31, 2018. The spot exchange rate of the Euro to the U.S. dollar was $1.14 per Euro at June 30, 2019, as compared to $1.12 per Euro at March 31, 2019. The 2018 loss was directly related to the decrease in the spot exchange rate of the Euro at June 30, 2018 as compared to March 31, 2018. The spot exchange rate of the Euro to the U.S. dollar was $1.17 per Euro at June 30, 2018, as compared to $1.23 per Euro at March 31, 2018.

Comparison for the six months ended June 30, 2019 and 2018:

Revenues:

Revenue from product sales was approximately $10,427,000 in the six months ended June 30, 2019, as compared to approximately $9,679,000 in the six months ended June 30, 2018, an increase of approximately $748,000, or 8%. This increase was driven by an increase in direct sales of approximately $1,160,000 resulting from sales to both new customers and repeat orders from existing customers, offset by a decrease in distributor sales of approximately $412,000. In addition, sales were negatively impacted by approximately $737,000 as a result of the decrease in the average exchange rate of the Euro to the U.S. dollar. For the six months ended June 30, 2019, the average exchange rate of the Euro to the U.S. dollar was $1.13 as compared to an average exchange rate of $1.21 for the six months ended June 30, 2018.

Grant income was approximately $997,000 for the six months ended June 30, 2019 as compared to approximately $1,001,000 for the six months ended June 30, 2018, a decrease of approximately $4,000 or less than 1%.

Total revenues were approximately $11,424,000 for the six months ended June 30, 2019, as compared to total revenues of approximately $10,680,000 for the six months ended June 30, 2018, an increase of approximately $744,000, or 7%.

Cost of Revenues:

For the six months ended June 30, 2019 and 2018, cost of revenue was approximately $3,573,000 and $3,353,000, respectively, an increase of approximately $220,000. Product cost of revenues increased approximately $83,000 during the six months ended June 30, 2019 as compared to the six months ended June 30, 2018 due to increased sales. Product gross margins were approximately 75% for the six months ended June 30, 2019 and approximately 74% for the six months ended June 30, 2018.

Research and Development Expenses:

For the six months ended June 30, 2019, research and development expenses were approximately $5,348,000 as compared to research and development expenses of approximately $3,356,000 for the six months ended June 30, 2018. The increase of approximately $1,992,000 was due to increase in clinical trial costs of approximately $1,993,000, which is primarily related to our REFRESH 2-AKI trial, an increase in non-clinical research and development salary related costs of approximately $20,000 and an increase in other non-clinical research and development costs of approximately $186,000. These increases were offset by an increase in direct labor and other costs being deployed toward grant-funded activities of approximately $136,000, which had the effect of decreasing the amount of our non-reimbursable research and development costs, and a decrease in new product development costs of approximately $71,000.

Legal, Financial and Other Consulting Expense:

Legal, financial and other consulting expenses were approximately $1,154,000 for the six months ended June 30, 2019, as compared to approximately $874,000 for the six months ended June 30, 2018. The increase of approximately $280,000 was due to an increase in legal fees of approximately $194,000 related to patent matters and certain corporate initiatives, an increase in consulting fees of approximately $73,000, and an increase in accounting fees of approximately $17,000. These increases were offset by a decrease in employment agency fees of approximately $4,000.

Selling, General and Administrative Expense:

Selling, general and administrative expenses were approximately $9,265,000 for the six months ended June 30, 2019, as compared to approximately $10,385,000 for the six months ending June 30, 2018. The decrease of $1,120,000 was due to a decrease in non-cash stock compensation of approximately $2,426,000 and other general and administrative expenses of approximately $140,000. These decreases were offset by an increase in salaries, commissions and related costs of approximately $1,142,000, an increase in travel and entertainment and other costs of approximately $33,000, additional sales and marketing costs, which include advertising and conferences of approximately $189,000, an increase in royalty expenses of approximately $60,000 due to the increase in product sales and an increase in rent expense of approximately $22,000 related to the expansion of manufacturing and office facilities.

Interest Expense, net:

For the six months ended June 30, 2019, interest expense was approximately $420,000, as compared to interest expense of approximately $1,079,000 for the six months ended June 30, 2018. This decrease in interest expense of approximately $659,000 was primarily a result of the settlement of the Success Fee with Bridge Bank in the amount of $637,000 that became due in May 2018 in accordance with the terms of the 2016 Success Fee Letter with Bridge Bank and interest earned on our cash balances during the six months ended June 30, 2019.

Gain (Loss) on Foreign Currency Transactions:

For the six months ended June 30, 2019, the loss on foreign currency transactions was approximately $96,000 as compared to a loss of approximately $435,000 for the six months ended June 30, 2018. The 2019 loss was directly related to the decrease in the spot exchange rate of the Euro to the U.S. dollar at June 30, 2019 as compared to December 31, 2018. The spot exchange rate of the Euro to the U.S. dollar was $1.14 per Euro at June 30, 2019, as compared to $1.15 per Euro at December 31, 2018. The 2018 loss was directly related to the decrease in the spot exchange rate of the Euro at June 30, 2018 as compared to the December 31, 2017. The spot exchange rate of the Euro to the U.S. dollar was $1.17 per Euro at June 30, 2018, as compared to $1.20 per Euro at December 31, 2017.

History of Operating Losses:

We have experienced substantial operating losses since inception. As of June 30, 2019, we had an accumulated deficit of approximately $177,955,000, which included losses of approximately $8,431,000 and $8,803,000 for the six-month periods ended June 30, 2019 and 2018, respectively. Historically, losses have resulted principally from costs incurred in the research and development of our polymer technology, clinical studies, and general and administrative expenses.

Liquidity and Capital Resources:

Since inception, our operations have been primarily financed through the issuance of debt and equity securities. At June 30, 2019, we had current assets of approximately $22,214,000 including cash on hand of approximately $16,342,000 and current liabilities of approximately $6,919,000. On July 31, 2019, the Company executed an Amendment to its Loan Agreement with Bridge Bank and simultaneous with this Amendment received $5 million in proceeds from an additional term loan. In addition, the Amendment extends the interest only period of the loan for an additional six months through April 2020, with the ability to further extend the interest-only period for another six months through October 2020 should the Company meet certain conditions.

We believe that we have sufficient cash to fund our operations into 2020.

2019 Third Quarter Revenue Guidance:

CytoSorbents has not historically given specific financial guidance on quarterly results until the quarter has been completed. However, we expect our third quarter 2019 product sales will exceed sales reported in the third quarter of 2018. In addition, we expect that second half 2019 product sales will exceed first half 2019 product sales.

For additional information, please see the Company’s Annual Report on Form 10-K for the year ended December 31, 2018 filed on March 7, 2019 on View Source

On August 6, 2019 Alder BioPharmaceuticals, Inc. (NASDAQ: ALDR), a biopharmaceutical company focused on developing novel therapeutic antibodies for the treatment of migraine, reported its financial results for the second quarter ended June 30, 2019 (Press release, Alder Biopharmaceuticals, AUG 6, 2019, View Source [SID1234538253]).

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"We continue to make significant progress toward the potential launch of eptinezumab in the U.S. in the first quarter of 2020. We have our commercial leadership team in place, with experienced personnel leading sales, marketing and market access. The team is sharpening our go-to-market strategy and expects to complete our commercial footprint later this year. We recently presented additional data further confirming eptinezumab’s differentiated clinical profile and benefits in patient-reported outcomes at the 2019 American Headache Society and American Academy of Neurology Annual Meetings," said Bob Azelby, Alder’s president and chief executive officer. "Looking forward, we believe there is a large opportunity to build value at Alder in the latter half of the year, with the initiation of eptinezumab’s acute study and the advancement of our product candidate, ALD1910, into the clinic. These collective activities align with our mission to forever change the migraine treatment landscape and give people with migraines their lives back."

Second Quarter 2019 Highlights and Recent Developments

Commercial readiness activities ongoing under the leadership of recently appointed chief commercial officer, Nadia Dac: As Alder prepares for the potential commercial launch of eptinezumab in the U.S. in the first quarter of 2020, the company has conducted new market research that further confirms eptinezumab’s differentiated profile and is prepared to begin account-level engagement with payers. The company plans to focus its marketing efforts on the high-prescribing headache specialist population and accounts, where eptinezumab fits well into their treatment protocols of quarterly patient visits with its short, 30-minute IV administration and its well-tolerated safety profile, as demonstrated in the company’s clinical trials. The company plans to utilize a specialty sales organization sized between 75 and 100 sales representatives.

New migraine-free months, migraine severity and quality of life data presented at AHS Annual Meeting: In July 2019, Alder presented new data from post-hoc analyses from its PROMISE 1 and PROMISE 2 Phase 3 clinical trials for eptinezumab at the American Headache Society’s (AHS) 61st Annual Scientific Meeting in Philadelphia, PA from July 11-14, 2019. Key highlights from the new data presented show 18.1% of episodic migraine patients treated with 100 mg of eptinezumab experienced no migraine days for at least half of the study period (≥six months), compared with 12.6% of placebo-treated patients, and 14.0% of chronic migraine patients treated with 100 mg of eptinezumab experienced no migraine days for at least half of the study period (≥three months), compared with 4.9% of placebo-treated patients. Data presented from PROMISE 2 also showed consistent clinically significant improvements in migraine severity in chronic migraine patients, a large contributor to impact on quality of life, starting at Month 1. Eptinezumab treatment resulted in clinically meaningful improvements in Headache Impact Test (HIT-6) scores in chronic migraine patients as early as Month 1 after treatment, which were maintained or further improved throughout the six-month study period, compared to placebo, which did not achieve a clinically meaningful improvement until Month 6. In addition, eptinezumab treatment resulted in clinically meaningful improvements greater than placebo in the 36-item Short-Form Health Survey (SF-36) scores in chronic migraine patients as early as Month 1 after treatment and through the six-month study period. From a safety perspective, longer-term exposure has demonstrated no change in the overall safety profile for eptinezumab.

Data showing consistency of rapid onset of migraine prevention and improvements in most bothersome migraine symptoms and patient reported outcomes data presented at AAN Annual Meeting: In May 2019, Alder presented efficacy data highlighting the consistency of the rapid onset of migraine prevention across four clinical trials with eptinezumab at the 71st American Academy of Neurology (AAN) Annual Meeting in Philadelphia, PA from May 4-10, 2019. Across the Phase 2 and Phase 3 clinical trials, it was observed that eptinezumab, with its 100% bioavailability at the end of infusion, showed a rapid onset of migraine prevention. The rapid response observed on both Day 1 and through Month 1 in PROMISE 1 and PROMISE 2 was also sustained through the first quarter following a single eptinezumab infusion, and was maintained or further increased through subsequent infusions. Alder also presented a new analysis of patient-reported outcomes data from the PROMISE 2 Phase 3 clinical trial of eptinezumab for the prevention of chronic migraine, showing improvements in the most bothersome migraine symptoms and patients’ global impression of change in their migraine status by Month 1 after treatment, with improvements sustained in overall response through the first and second quarterly infusions.

Upcoming Anticipated Milestones

Eptinezumab PDUFA target action date set for early 2020: The U.S. Food and Drug Administration (FDA) accepted the Biologics License Application (BLA) filing for eptinezumab in April 2019, and set a Prescription Drug User Fee Act (PDUFA) target action date of February 21, 2020. If approved, eptinezumab will be the first-to-market IV therapy for migraine prevention, providing rapid and sustained prevention that begins on Day 1.

Acute study for eptinezumab to begin in 2H 2019: Alder plans to initiate a Phase 3 clinical trial evaluating eptinezumab as a treatment for acute migraine in patients who are candidates for prevention therapy in the second half of 2019. The trial will seek to leverage eptinezumab’s 100% bioavailability and rapid onset of prevention demonstrated in clinical testing, with the objective of securing an indication for the acute treatment of migraine for patients and positioning eptinezumab as the first anti-CGRP monoclonal antibody for both the treatment and prevention of migraine, if approved for both these indications.

ALD1910 to enter clinical development in 2019: Alder continues to advance its preclinical candidate, ALD1910, a monoclonal antibody targeting PACAP (pituitary adenylate cyclase-activating peptide) for migraine prevention. ALD1910 is currently undergoing Investigational New Drug (IND)-enabling preclinical studies. Alder expects to initiate a first in-human clinical study by the end of 2019.

Second Quarter 2019 Financial Results

As of June 30, 2019, Alder had $440.7 million in cash, cash equivalents, investments and restricted cash, compared to $412.4 million as of December 31, 2018.

Research and development expenses for the second quarter ended June 30, 2019 totaled $34.1 million, compared to $52.8 million for the same period in 2018. The year-over-year decrease was primarily due to a decrease in process development costs and a decrease in clinical trial costs due to the completion of patient treatments for several of the company’s clinical trials.

General and administrative expenses for the second quarter ended June 30, 2019 totaled $21.6 million, compared to $11.9 million for the same period in 2018. The year-over-year increase reflects efforts to support commercial readiness activities for eptinezumab.

Net loss applicable to common stockholders for the second quarter ended June 30, 2019 totaled $59.9 million, or $0.72 per share, compared to net loss of $70.7 million, or $1.04 per share on a fully-diluted basis, for the same period in 2018.

Financial Outlook

Alder continues to expect that full-year 2019 net cash used in operating activities and purchases of property and equipment will be in the range of $285 to $315 million. The majority of the spend is focused on ensuring that Alder is prepared for the potential launch of eptinezumab in the first quarter of 2020, including advancing eptinezumab’s supply chain, building commercial inventory, continuing to build out Alder’s commercial footprint and other pre-launch market readiness activities.

Alder believes its available cash, cash equivalents, investments and restricted cash will be sufficient to meet its projected operating requirements through the anticipated launch of eptinezumab and into the latter part of 2020.

Conference Call and Webcast

Alder will host a conference call today at 5:00 p.m. ET to discuss these financial results and recent corporate highlights. The live call may be accessed by dialing (877) 430-4657 for domestic callers or (484) 756-4339 for international callers, and providing conference ID number 6561825. The webcast will be broadcast live and can be accessed from the Events & Presentations page in the Investors section of Alder’s website at www.alderbio.com. The webcast will be available for replay following the call for at least 30 days.

On August 6, 2019 Evelo Biosciences, Inc. (Nasdaq:EVLO), a biotechnology company developing oral biologics that act on cells in the small intestine with systemic therapeutic effects, reported positive interim Phase 1b clinical data and provided second quarter 2019 financial results (Press release, Evelo Biosciences, AUG 6, 2019, View Source [SID1234538196]).

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"Evelo is harnessing the therapeutic potential of cells in the small intestine which play a central role in governing the immune, metabolic, and nervous systems. Our platform has generated a diversified portfolio of oral biologic candidates that act on these cells to drive systemic effects relevant to the potential treatment of a broad range of diseases," said Simba Gill, Ph.D., chief executive officer of Evelo. "Today’s positive interim data show, for the first time in patients, clinical and biomarker responses that support our core scientific hypothesis and our vision of developing effective, oral, safe, and affordable medicines for people with major chronic diseases and cancer. We look forward to advancing into later stage trials and continuing to expand our clinical portfolio."

Inflammation: Interim Clinical Data Highlights and Anticipated Milestones

About the EDP1815 and EDP1066 Phase 1b clinical trials
Each of EDP1815 and EDP1066 are in ongoing signal-finding Phase 1b clinical trials in mild to moderate psoriasis and atopic dermatitis. Patients in these trials are randomized 2:1 to receive daily, oral administration of active drug, or placebo, for 28 days. The primary endpoint of these trials is safety and tolerability. Prospectively defined secondary and exploratory endpoints include clinical measures of disease, cellular histological biomarkers and blood immune cell biomarkers taken from biopsies and blood samples, respectively, at the start and end of the 28-day dosing period.

EDP1815 – positive interim Phase 1b clinical data at low dose in mild to moderate psoriasis patients

In a separate press release this morning Evelo reported positive EDP1815 clinical data from an initial 12-patient cohort in its ongoing trial in mild to moderate psoriasis.

EDP1815 was well tolerated with no overall difference reported from placebo.

Patients dosed once per day for 28 days with 550mg (1x dose) of the enteric capsule formulation of EDP1815 showed a statistically significant (p>0.05) reduction in mean lesion severity score (LSS) at 28 days of 2 points, compared to a mean increase of 0.25 points in patients who received placebo. LSS reductions over the dosing period of patients dosed with EDP1815 ranged from 0-67 percent. LSS, a secondary endpoint, is a component of the Psoriasis Area and Severity Index (PASI) score and measures redness, thickness, and scaling of an individual psoriatic lesion across the dosing period and is a sensitive clinical measure for patients with mild to moderate disease.

Analysis of the basal epithelium mitotic count, a secondary endpoint and cellular driver of psoriasis pathology, showed a mean reduction over the dosing period of 2.25 cells/mm2 in patients who received EDP1815 compared to no change in patients receiving placebo. Lower basal epithelium mitotic counts indicate a reduction of psoriasis pathology.

In an analysis of the change over the dosing period of blood immune cell cytokine production following stimulation with lipopolysaccharide, an exploratory endpoint, the EDP1815 dosed patient group showed a reduction in cytokine production indicative of a systemic anti-inflammatory response, compared to no reduction in the placebo group.

Based on these data, Evelo plans to advance EDP1815 into Phase 2 in early 2020. This placebo-controlled dose and formulation optimization trial will investigate daily dosing of EDP1815 in mild to moderate psoriasis patients over 24 weeks.

Enrollment is underway in the ongoing Phase 1b clinical trial of an additional cohort of mild to moderate psoriasis patients to be dosed at a 2.76g (5x) dose of the enteric capsule formulation. Data from this cohort are expected in the fourth quarter of 2019.

EDP1066 – positive interim Phase 1b biomarker data at high dose in mild to moderate psoriasis patients

Today, Evelo reports positive EDP1066 biomarker data at the high dose from its ongoing Phase 1b trial in patients with mild to moderate psoriasis.

EDP1066 was well tolerated with no overall difference reported from placebo.

In an analysis of the change over the dosing period of blood immune cell cytokine production following stimulation by lipopolysaccharide, an exploratory endpoint, patients who received a 3.3g (5x) dose of EDP1066 showed a reduction in cytokine production consistent with a pharmacodynamic effect. No reduction was observed in patients receiving a 660mg (1x) dose of EDP1066 or placebo.

No effects were observed in the secondary endpoints of clinical measures of disease or cellular histological biomarkers at either the 660mg or 3.3g dose of EDP1066.

Evelo is focusing the current EDP1066 Phase 1b trial on investigating the activity of a new formulation, which was up to 30-fold more potent in preclinical models, in a cohort of mild to moderate atopic dermatitis patients. Evelo expects to report data from this cohort in the first quarter of 2020.

Given the EDP1815 data, Evelo will not develop EDP1066 any further in psoriasis.

Oncology: Clinical Studies and Anticipated Milestones

EDP1503 – Phase 1/2

Evelo is conducting a Phase 1/2 clinical trial of EDP1503 in combination with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, in microsatellite stable colorectal cancer, triple-negative breast cancer, and patients with other tumor types that have relapsed on prior PD-1/L1 inhibitor treatment. Initial clinical data is expected in the first half of 2020.

EDP1503 – Phase 2a

The University of Chicago is conducting a Phase 2a investigator-sponsored clinical trial of EDP1503 in combination with KEYTRUDA in naive melanoma patients and melanoma patients who have relapsed on prior PD-1/L1 inhibitor treatment. Evelo will no longer be providing guidance as to timing related to this investigator-sponsored trial.

Business Highlights

In June 2019, Evelo appointed Jose-Carlos Gutiérrez-Ramos, Ph.D. to its board of directors. Dr. Gutiérrez-Ramos brings to the board significant experience in research, clinical development and company building over a long career in senior leadership roles at major pharmaceutical and biotech companies. Dr. Gutiérrez-Ramos has served as chief executive officer and president of Cogen Immune Medicine, Inc., a biotechnology company, since August 2018. Dr. Gutiérrez-Ramos has also served as a venture partner at Flagship Pioneering since 2018. From 2015 to May 2018 he served as chief executive officer and president of Synlogic, Inc. Prior to joining Synlogic, Dr. Gutiérrez-Ramos was group senior vice president of Worldwide Research and Development and global head of Biotherapeutics Research and Development at Pfizer, Inc. Dr. Gutiérrez-Ramos received a B.S. from Universidad Complutense de Madrid and his Ph.D. in immunochemistry from the Universidad Autonoma de Madrid.

In July 2019, Evelo entered into a loan and security agreement with K2 HealthVentures (K2HV). Under the terms of the agreement, Evelo can borrow up to $45 million subject to certain time conditions and clinical development milestones. On closing, Evelo borrowed $20 million; the funds were used to fully repay its $15 million loan facility with Pacific Western Bank and for general corporate purposes.

In July 2019, Evelo entered into a collaboration agreement with Sacco S.r.l. (Sacco), an existing contract manufacturing partner. Under the terms of this 5-year agreement, Sacco will manufacture and supply single strain, non-genetically modified microbes for oral delivery or oral use in pharmaceutical products exclusively for Evelo, with the exception of pre-existing products for pre-existing customers. This collaboration is consistent with Evelo’s manufacturing strategy of combining best-in-class manufacturing partners with internal manufacturing capacity and deep internal expertise in process development and formulation.

Second Quarter 2019 Financial Results

Cash Position: As of June 30, 2019, cash, cash equivalents and investments were $113.5 million, as compared to $178.9 million as of June 30, 2018 and $129.4 million as of March 31, 2019. This decrease was due to cash used to fund operating activities and capital expenditures. Evelo expects that its cash, cash equivalents and investments will enable it to fund its planned operating expenses and capital expenditure requirements, including the planned EDP1815 Phase 2 clinical trial, into the fourth quarter of 2020.

Research and Development Expenses: R&D expenses were $15.5 million for the three months ended June 30, 2019, compared to $10.2 million for the three months ended June 30, 2018. The increase of $5.3 million was due primarily to increases in costs related to Evelo’s inflammation and oncology clinical development programs, and research platform expenses, as well as increased personnel costs.

General and Administrative Expenses: G&A expenses were $5.9 million for the three months ended June 30, 2019, compared to $5.1 million for the three months ended June 30, 2018. The increase of $0.8 million was due primarily to increased personnel costs and professional and consulting fees necessary to support Evelo’s growing organization and corporate operational activities.

Net Loss: Net loss attributable to common stockholders was $20.9 million for the three months ended June 30, 2019, or $(0.65) per basic and diluted share, as compared to a net loss attributable to common stockholders of $16.7 million for the three months ended June 30, 2018, or $(0.85) per basic and diluted share.

Conference Call
Evelo will host a conference call and webcast to discuss these data and the second quarter financial results today at 8:30 a.m. ET. To access the call please dial 866-795-3242 (domestic) and 409-937-8909 (international) and provide the passcode 6380636. A live webcast of the call, including an accompanying slide presentation, will be available on the Investors sections of the Evelo website at www.evelobio.com. The archived webcast will be available approximately two hours after the conference call and will be available for 30 days following the call.

On August 6, 2019 Oncternal Therapeutics, Inc., (Nasdaq: ONCT) a clinical-stage biotechnology company developing potential first-in-class product candidates for cancers with critical unmet medical need, reported that it has opened for enrollment its randomized Phase 2 study of cirmtuzumab, a ROR1-targeted monoclonal antibody, combined with ibrutinib in patients with chronic lymphocytic leukemia (CLL) (Press release, Oncternal Therapeutics, AUG 6, 2019, View Source [SID1234538212]). The decision to open Phase 2 of the company’s ongoing Phase 1/2 CIRLL (Cirmtuzumab and Ibrutinib targeting ROR1 for Leukemia and Lymphoma) clinical trial was triggered by favorable outcomes from the Part 1 dose-finding and Part 2 dose-confirming cohorts of the clinical trial, including an observed interim objective response rate (ORR) of 100% for the first 9 CLL patients with evaluable data receiving the recommended dosing regimen who have completed 12 weeks of cirmtuzumab plus ibrutinib treatment in Part 2, and a well-tolerated safety profile consistent with that seen with ibrutinib treatment alone.

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In June, the company presented data at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting, reporting that results from the first 12 patients with CLL treated in Part 1 of the Phase 1 portion of the study showed an observed interim objective response rate (ORR) of 91.7% for the combination of cirmtuzumab plus ibrutinib, including three patients with clinical or confirmed complete responses, and a well-tolerated safety profile consistent with that seen for ibrutinib treatment alone.

Included in the results presented at ASCO (Free ASCO Whitepaper) were preliminary results from six patients with mantle cell lymphoma (MCL), who were treated in a separate cohort of the CIRLL study. Data from this cohort will be presented at a future medical conference. One patient with MCL who had relapsed following an allogeneic stem cell transplant experienced a confirmed complete response (CR) after 3 months of cirmtuzumab plus ibrutinib treatment, including complete resolution of a large mediastinal mass. This CR appears to be durable, and has been confirmed after 6, 9 and 11 months of cirmtuzumab plus ibrutinib treatment.

The CIRLL clinical trial is supported by a grant from the California Institute for Regenerative Medicine (CIRM) and is being conducted in collaboration with the University of California at San Diego (UC San Diego).

"We are very pleased to be opening the randomized Phase 2 portion of the CIRLL study for patients with CLL and continue to be encouraged by the interim results from the study for both patients with CLL and patients with mantle cell lymphoma," said James Breitmeyer, M.D., Ph.D., Oncternal’s President and CEO.

About the Study
The CIRLL Study (CIRM-0001) is a Phase 1/2 clinical trial evaluating cirmtuzumab in combination with ibrutinib in patients with CLL or MCL. Part 1 of the study was a Phase 1 dose-finding portion designed to determine the Phase 2 dose, or recommended dosing regimen (RDR). Part 2 was a Phase 1b expansion cohort to confirm the RDR. Interim analyses were specified for Part 1 and Part 2. Part 3 of the study, which is now open for enrollment, is a Phase 2 study in which approximately 90 patients with CLL will be randomized to receive either ibrutinib alone or ibrutinib plus cirmtuzumab, with a primary endpoint of complete response rate. An interim assessment of the first 12 patients with CLL enrolled in Part 1 of the study was presented as a poster at the 2019 ASCO (Free ASCO Whitepaper) Annual Meeting. Additional information about the CIRM-0001 study and other clinical studies of cirmtuzumab may be accessed at ClinicalTrials.gov.

About Cirmtuzumab
Cirmtuzumab is an investigational, potentially first-in-class monoclonal antibody targeting ROR1, or Receptor tyrosine kinase-like Orphan Receptor 1. Cirmtuzumab is currently in a Phase 1/2 clinical trial in combination with ibrutinib for the treatment of CLL and MCL, in a collaboration with the University of California San Diego School of Medicine and the California Institute for Regenerative Medicine. In addition, an investigator-initiated Phase 1 clinical trial of cirmtuzumab in combination with paclitaxel for women with metastatic breast cancer is being conducted at the UC San Diego School of Medicine. CIRM has also provided funding to support development programs for cirmtuzumab and a CAR-T product candidate that targets ROR1, which is currently in preclinical development as a potential treatment for hematologic cancers and solid tumors.

When expressed by hematologic malignancies such as CLL and MCL, ROR1 acts as a receptor for the tumor growth factor Wnt5a. Researchers at the UC San Diego School of Medicine discovered that targeting a critical epitope on ROR1 was key to inhibiting Wnt5a activation, specifically targeting ROR1 expressing tumors, and this finding led to the discovery of the potent and highly selective antitumor activity of cirmtuzumab observed in preclinical studies. Oncternal believes ROR1 is an attractive target for cancer therapy because it is an oncofetal antigen – a protein not normally expressed in adults, but which confers a survival and fitness advantage when reactivated and expressed by tumor cells. Preclinical data indicate that when cirmtuzumab binds to ROR1, it blocks Wnt5a signaling, induces differentiation of the tumor cells, and inhibits tumor cell proliferation, migration and survival. Cirmtuzumab is in clinical development and has not been approved by the U.S. Food and Drug Administration for any indication.