On February 25, 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 fourth quarter and full year ended December 31, 2018 (Press release, Alder Biopharmaceuticals, FEB 25, 2019, View Source [SID1234533649]). Alder also noted that it announced the completion of its Biologics License Application (BLA) submission for eptinezumab, the company’s investigational monoclonal antibody (mAb) for migraine prevention targeting the calcitonin gene-related peptide and lead commercial candidate, with the Food and Drug Administration (FDA) on February 22, 2019.

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r Alder, capped by the completion of eptinezumab’s BLA submission to the FDA last week," said Bob Azelby, president and chief executive officer of Alder. "We achieved all of the significant milestones we targeted for the year including positive top-line data from our PROMISE 2 Phase 3 clinical trial and positive PROMISE 1 and PROMISE 2 Phase 3 data demonstrating sustained or increased migraine prevention following subsequent infusions, as well as positive results from a pharmacokinetic study, to name a few. The achievement of these milestones further demonstrates eptinezumab’s differentiated profile, which we believe will allow Alder to compete in the highly impacted migraine patient segment."

Mr. Azelby added, "As we look ahead to 2019, we continue to make substantial progress advancing our supply chain, building commercial inventory, expanding our commercial and operational infrastructure, and executing on key pre-launch initiatives to enable a successful commercial launch of eptinezumab in the first quarter of 2020, if approved. Additionally, consistent with our commitment to forever change migraine treatment and give patients their lives back, we are focused on advancing our pre-clinical candidate, ALD1910. The totality of our pre-clinical data to date gives us confidence that we will be positioned to initiate a first in-human clinical trial by the end of 2019."

2019 Highlights and Upcoming Milestones

On February 22, Alder announced it completed its BLA submission for eptinezumab with the FDA. The BLA submission was supported by positive results from Alder’s two positive Phase 3 trials of eptinezumab, positive results from an open-label safety study and a pharmacokinetic (PK) comparability study, and chemistry, manufacturing, and controls (CMC) data packages.

Alder remains on track for the potential commercial launch of eptinezumab in the first quarter of 2020, and continues to advance its manufacturing and commercial readiness activities in anticipation of launch. Currently, Alder is advancing its supply chain, building commercial inventory, continuing to build out its commercial and operational infrastructure, and executing against other key pre-launch initiatives.

Alder continues to advance its pre-clinical candidate, ALD1910, a monoclonal antibody targeting PACAP-38 (pituitary adenylate cyclase-activating peptide-38). ALD1910 is currently undergoing Investigational New Drug (IND)-enabling preclinical studies and Alder expects to initiate its first in-human clinical study by the end of 2019.

In January, Alder announced the appointment of Dr. Paul Streck as Chief Medical Officer. He brings more than 25 years of experience in drug development, regulatory and medical affairs leadership across both large and small publicly traded biopharmaceutical companies. Dr. Streck previously served as Chief Medical Officer at Insmed Incorporated, where he played an instrumental role as a member of the executive leadership team and successfully led the Arikayce regulatory filing, approval and launch.

2018 Company Milestones

In December, Alder announced the appointment of Carlos Campoy as Chief Financial Officer. He brings nearly 30 years of financial leadership and expertise across global publicly-traded companies, including more than 20 years in the biopharmaceutical and healthcare sectors. Mr. Campoy previously served as Vice President of Finance, International at Allergan plc, where he had financial responsibility for $3B in sales and drove significant growth across all product divisions, including Neurosciences and BOTOXÒ.

In October, Alder announced positive results from a comparative PK study that supported the comparability evaluation of the clinical supply for eptinezumab and its planned commercial supply. Both the primary and key secondary PK results met the standard pre-specified acceptance criteria for drug product comparability.

In June, new data from Alder’s PROMISE 1 and PROMISE 2 Phase 3 clinical trials for eptinezumab in episodic and chronic migraine patients, respectively, were presented at the American Headache Society Meeting. The new data highlighted the strength of eptinezumab’s efficacy data by showing sustained or increased efficacy following subsequent quarterly administrations of eptinezumab.

In April, new data from Alder’s PROMISE 1 Phase 3 clinical trial for eptinezumab in episodic migraine patients were presented at the 70th Annual AAN Meeting. The new data demonstrated long-term and sustained or further increased efficacy in episodic migraine following the third and fourth quarterly infusion, as well as increased migraine-free intervals and improved quality of life outcomes.

Also in the second quarter of 2018, Alder completed a one-year safety study of eptinezumab, which generated favorable safety and tolerability data and demonstrated a favorable safety profile consistent with previous eptinezumab studies.

In January, Alder announced eptinezumab significantly reduced migraine risk and met the primary and all key secondary endpoints in its pivotal PROMISE 2 Phase 3 clinical trial for chronic migraine prevention.

Also in January 2018, Alder entered into a settlement and global license agreement with Teva Pharmaceuticals International GmbH, which provided clarity regarding Alder’s freedom to develop, manufacture and commercialize eptinezumab in the U.S. and globally.

Fourth Quarter and Year-End 2018 Financial Results

As of December 31, 2018, Alder had $412.4 million in cash and cash equivalents, short-term investments and restricted cash, compared to $484.7 million as of Sept. 30, 2018 and compared to $286.2 million as of December 31, 2017.

Research and development expenses for the fourth quarter ended December 31, 2018 totaled $64.4 million, compared to $44.7 million for the same period in 2017. For the full year 2018, research and development expenses totaled $239.1 million, compared to $252.9 million for the full year 2017. The year-over-year decrease was primarily due to lower clinical trial costs in 2018 as a result of the completion of several clinical trials.

General and administrative expenses for the fourth quarter ended December 31, 2018 totaled $13.0 million, compared to $10.3 million for the same period in 2017. For the full year 2018, general and administrative expenses totaled $47.5 million, compared to $38.1 million for the full year 2017. The year-over-year increases reflect Alder’s continued commitment to advance the eptinezumab program and position Alder for commercialization.

Net loss applicable to common stockholders for the fourth quarter ended December 31, 2018 totaled $81.5 million, or $1.19 per share, compared to net loss of $54.4 million, or $0.80 per share on a fully-diluted basis, for the same period in 2017. For the full year 2018, net loss applicable to common stockholders totaled $331.9 million, or $4.87 per share on a fully-diluted basis, compared to net loss of $288.9 million, or $4.95 per share, for the full year 2017.

Financial Outlook

Alder expects 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 dollars. 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, short-term investments and restricted cash will be sufficient to meet the company’s projected operating requirements into 2020 and the anticipated launch of eptinezumab.

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 7655239. 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 February 25, 2019 Horizon Pharma plc (Nasdaq: HZNP), reported that the company will participate in the following conference in March (Press release, Horizon Biopharm, FEB 25, 2019, View Source [SID1234533631]):

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Cowen and Company 39th Annual Health Care Conference

Date: March 11, 2019
Presentation Time: 12 p.m. ET
Location: Boston
The conference presentation will be webcast live and may be accessed by visiting Horizon’s website at View Source A replay of the webcast will be available for the event.

On February 25, 2019 CRISPR Therapeutics (NASDAQ: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, reported financial results for the fourth quarter and full year ended December 31, 2018 (Press release, CRISPR Therapeutics, FEB 25, 2019, View Source [SID1234533633]).

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"This past year was truly transformational for CRISPR Therapeutics as we achieved milestones across our key programs in β-thalassemia, sickle cell disease and immuno-oncology. We’re pleased with the progress we’ve made in 2018, especially in clinical execution and the expansion of our development pipeline. We also strengthened our team with key new hires, positioning us well as we advance to the next stage of development. This progress brings us closer to realizing our mission of bringing transformative therapies to patients with serious diseases," said Samarth Kulkarni, Ph.D., Chief Executive Officer of CRISPR Therapeutics.

Dr. Kulkarni added: "Over the next two years, we expect to generate data from clinical trials across multiple indications as we bring CRISPR technology to patients. In addition, we are making deliberate steps to scale the Company as we advance programs across a number of therapeutic areas while continuing to bolster our proprietary CRISPR platform."

Recent Highlights and Outlook

Hemoglobinopathies

° β-thalassemia
CRISPR Therapeutics, together with its partner, Vertex, announced that the first patient has been treated with CTX001 in a Phase 1/2 clinical study of patients with transfusion-dependent beta thalassemia (TDT), marking the first company-sponsored use of a CRISPR/Cas9 therapy in a clinical trial. The Phase 1/2 open-label trial is designed to assess the safety and efficacy of a single dose of CTX001 in patients ages 18 to 35 with TDT, non-beta zero/beta zero subtypes. The first two patients in the trial will be treated sequentially and, pending data from these initial two patients, the trial will open for broader concurrent enrollment. The companies plan to target presentations of data at scientific conferences once there is sufficient data on multiple patients.

° Sickle Cell Disease
CRISPR Therapeutics, together with its partner, Vertex, are also investigating CTX001 for the treatment of severe sickle cell disease (SCD) and announced that the first patient has been enrolled in a Phase 1/2 clinical study of CTX001 in severe SCD in the U.S. and is expected to be infused with CTX001 in mid-2019. The Phase 1/2 open-label trial is designed to assess the safety and efficacy of a single dose of CTX001 in patients ages 18 to 35 with severe SCD. Similar to the trial in beta thalassemia, the first two patients in the trial will be treated sequentially prior to broader concurrent enrollment. The companies plan to target presentations of data at scientific conferences once there is sufficient data on multiple patients. CTX001 was recently granted Fast Track Designation by the U.S. Food and Drug Administration for the treatment of SCD.
Immuno-Oncology

° CRISPR Therapeutics is on track to initiate a clinical trial for CTX110, its wholly-owned allogeneic CAR-T cell therapy targeting CD19+ malignancies, in the first half of 2019. CRISPR/Cas9 has the potential to create the next-generation of CAR-T cell therapies that may have a superior product profile compared to current autologous therapies and allow accessibility to broader patient populations. The Company continues to advance two additional allogeneic CAR-T candidates; CTX120, targeting B-cell maturation antigen (BCMA) for the treatment of multiple myeloma; and CTX130, targeted towards CD70 for the treatment of both solid tumors and hematologic malignancies. In November, the Company presented a poster at the Society for Immunotherapy in Cancer (SITC) (Free SITC Whitepaper) 33rd Annual Meeting related to multiplex editing and production of allogeneic CAR-T therapies. Additionally, the Company presented a poster at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2018 Annual Meeting in December, highlighting further development and preclinical data for CTX120. The study showed maintained cytotoxic capacity over multiple in vitro re-challenges, demonstrating durable potency and reduced susceptibility to exhaustion.
Other Programs

° In September, CRISPR Therapeutics and ViaCyte, Inc. announced a collaboration focused on the discovery, development, and commercialization of gene-edited allogeneic stem cell derived islet cell progenitors which may offer curative benefit to patients with insulin-requiring diabetes. The combination of ViaCyte’s stem cell capabilities and CRISPR Therapeutics’ gene editing capabilities has the potential to enable a beta-cell replacement product that may deliver durable benefit to patients without the need for immune suppression.

° Earlier this year, CRISPR Therapeutics announced strategic collaborations with StrideBio, Inc. and ProBioGen. The Company’s collaboration with StrideBio expands upon an existing agreement to generate engineered AAV capsids with improved properties for in vivo gene editing programs and now includes additional undisclosed applications. CRISPR Therapeutics and ProBioGen announced a collaboration focused on the development of novel in vivo delivery modalities for CRISPR/Cas9 leveraging ProBioGen’s existing technology and expertise.

° In November, CRISPR Therapeutics and MaxCyte announced the expansion of an existing collaboration by entering into a non-exclusive commercial license agreement allowing CRISPR Therapeutics to deploy MaxCyte’s Flow Electroporation Technology to develop CRISPR/Cas9-based therapies in immuno-oncology. The collaboration builds on an existing agreement which allowed for the development of commercial therapeutics for hemoglobin-related diseases.
Company Building

° CRISPR Therapeutics continued to expand core capabilities in critical areas with the addition of key new talent across several functions.

° In February, CRISPR Therapeutics proposed to elect John T. Greene and Katherine A. High, M.D. to its Board of Directors at the Company’s upcoming annual general meeting to be held later this year. Together, they will bring significant strategic and operational experience to CRISPR Therapeutics.
Fourth Quarter and Full Year 2018 Financial Results

Cash Position: Cash and cash equivalents as of December 31, 2018 were $456.6 million, compared to $239.8 million as of December 31, 2017, an increase of $216.8 million, which was primarily driven by the net proceeds of $307.1 million from the sale of shares in follow-on financing rounds executed in January and September of 2018, offset by the Company’s use of $96.2 million for operating activities.

Revenue: Total collaboration revenue was $0.1 million for the fourth quarter of 2018 compared to $32.3 million for fourth quarter of 2017, and $3.1 million for the year ended December 31, 2018, compared to $41.0 million for the year ended December 31, 2017. The decrease in annual revenue is primarily attributable to deferred revenue recognized in 2017 in conjunction with the execution of the Company’s collaboration agreement with Vertex. During 2018 and going forward, Vertex funding of hemoglobinopathies programs are categorized as a contra-expense as opposed to revenue.

R&D Expenses: R&D expenses were $28.8 million for the fourth quarter of 2018 compared to $20.0 million for the fourth quarter of 2017, and $113.8 million for the year ended December 31, 2018 compared to $69.8 million for the year ended December 31, 2017. The increase in expense for the year was driven by greater investment in CRISPR’s lead hemoglobinopathies program partnered with Vertex, one-time expense associated with beginning our ViaCyte collaboration and expenses from the Company’s wholly owned immuno-oncology and in vivo programs.

G&A Expenses: General and administrative expenses were $16.5 million for the fourth quarter of 2018 compared to $11.3 million for the fourth quarter of 2017, and $48.3 million for the year ended December 31, 2018 compared to $35.8 million for the year ended December 31, 2017. The increase in general and administrative expenses for the year was driven by increased professional services and employee-related costs associated with our growing organization.

Net Income/Loss: Net loss was $47.6 million for the fourth quarter of 2018 compared to income of $0.1 million for the fourth quarter of 2017, and net loss was $165.0 million for the year ended December 31, 2018 compared to a loss of $68.4 million for the year ended December 31, 2017.

On February 25, 2019 EORTC reported that resulted phase II 62043 and phase III 62072 published in Clinical Cancer Research, showed that in patients with soft tissue sarcoma, the concomitant use of gastric acid suppressant (GAS) therapy and the anticancer therapeutic pazopanib was associated with significantly reduced progression-free survival and overall survival.

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It is estimated that up to 50 percent of those undergoing cancer treatment utilize Gastric Acid Suppressant (GAS) therapy. Common GAS drugs include proton pump inhibitors, such as omeprazole and esomeprazole magnesium, or histamine H2-receptor blockers, such as ranitidine.

The absorption of pazopanib, a multi-kinase inhibitor used in the treatment of renal cell carcinoma and soft tissue sarcoma, is pH-dependent, noted Mir. "We know that pazopanib tablets taken orally need to go into an acidic environment, namely the stomach, in order to dissolve," he explained. "As the primary function of GAS therapy is to reduce the acidity in the stomach, these drugs can reduce the absorption of pazopanib," Mir continued.

Previous work has shown that GAS therapy reduced the absorption of pazopanib as measured in plasma in patients with solid tumors, noted Mir. "We wanted to determine if the use of GAS drugs had an effect on survival outcomes in sarcoma patients taking pazopanib," he said.

Mir and colleagues analyzed data from the completed EORTC phase II 62043 and phase III 62072 clinical trials of patients with advanced soft-tissue sarcoma treated with pazopanib. The researchers first compared the outcome of patients treated with pazopanib with or without gastric acid suppressive agents for ≥ 80% of treatment duration, and subsequently using various thresholds. 333 patients treated with pazopanib were eligible for analysis; of these, 117 (35.1 percent) received GAS drugs at least once during pazopanib treatment, 59 (17.7 percent) utilized GAS therapy concomitantly for more than 80 percent of pazopanib treatment duration, and 19 (5.7 percent) were already utilizing GAS drugs at the time of trial registration.

Following multivariable analysis, compared to patients who did not use GAS therapy during pazopanib treatment, those who concomitantly utilized GAS for at least 80 percent of treatment duration had significantly reduced progression-free survival (median of 4.6 months compared to 2.8 months, respectively). Concomitant use of GAS also significantly reduced overall survival; those who utilized GAS therapy for at least 80 percent of treatment duration had shorter median overall survival (8 months) compared to those who did not use GAS therapy (12.6 months).

Among the 110 placebo-treated patients from the phase III trial who were eligible for analysis, there were no associations between concomitant GAS use and progression-free survival or overall survival. "This suggests that the drug-drug interaction between GAS and pazopanib directly affected the survival outcomes of sarcoma patients," Mir said.

Mir and colleagues also found that GAS therapy did not reduce the frequency of pazopanib-related toxicities. "I think that our results are practice-changing, and I would discourage oncologists against prescribing gastric acid suppressants when patients are treated with pazopanib, unless it is the only option for the patient," Mir said.

"Patients often utilize GAS therapy for abdominal pain, which is not always related to stomach acidity," said Mir. "I would predict that the majority of patients taking GAS drugs could utilize a different therapy to aid in their abdominal discomfort. Moreover, it is important for patients to inform their oncologists of all the medications that they are taking during cancer so that potential drug-drug interactions can be identified and avoided."

Limitations of this research include its retrospective nature. The analysis was based on the reported use of GAS therapy in the course of the trial, a relatively small sample size and a lack of pharmacokinetic data, which are not routinely collected in late-phase trials.

This study was sponsored by Fonds Cancer (FOCA) from Belgium.

On February 25, 2019 Hummingbird Bioscience reported it has been awarded a product development grant totalling $13.1 million from the Cancer Prevention and Research Institute of Texas (CPRIT) (Press release, Hummingbird Bioscience, FEB 25, 2019, View Source [SID1234554020]).

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The grant will support the Phase IA/B clinical trials of the company’s first-in-class anti-VISTA therapeutic antibody for the treatment of VISTA mediated suppression of anti-tumor immunity in solid tumors and lymphomas that are unresponsive to existing therapies. Hummingbird Bioscience is a systems-biology enabled biotech company focused on the discovery and development of novel cancer therapeutics.

The CPRIT review for this grant included an in-depth evaluation of HMBD-002, an antibody that uniquely neutralizes VISTA function, by a panel of scientific, medical, and industry experts. The evaluation included rigorous review of the pre-clinical data, as well as regulatory, research and development, and intellectual property due diligence.

The grant will support the Phase IA/B clinical study and preparatory steps including GMP manufacturing and Investigational New Drug (IND) submission for the HMBD-002 program. The grant will also support the relocation of the company’s U.S. headquarters to Texas. Clinical trials for HMBD-002 are anticipated to begin in 2020. Hummingbird Bioscience was the only successful application of its type for this grant cycle.

The award follows the recent announcement of Nobel Laureate James P. Allison, Ph.D. and Padmanee Sharma, M.D., Ph.D. joining Hummingbird’s Scientific Advisory Board.

"We are delighted to be awarded this highly-selective grant from CPRIT and to start building our operations in Texas," said Piers Ingram, Ph.D., CEO of Hummingbird Bioscience. "Our company applies systems biology approaches to generate uniquely differentiated therapeutic antibodies. We are thrilled CPRIT’s panel of experts agrees that developing this anti-VISTA immuno-oncology program has the potential to significantly benefit patients."