1stOncology™: Cancer Intelligence Service – Page 8684 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Aeterna Zentaris Reports Second Quarter 2021 Financial Results and Provides Pipeline Program Updates

On August 5, 2021 Aeterna Zentaris Inc. (NASDAQ: AEZS) (TSX: AEZS) ("Aeterna" or the "Company"), a specialty biopharmaceutical company developing and commercializing a diversified portfolio of pharmaceutical and diagnostic products, reported its financial and operating results for the second quarter ended June 30, 2021 (Press release, AEterna Zentaris, AUG 5, 2021, View Source;id=209178&p=2201538&I=1206939-c7Z3G6f3m8 [SID1234585927]). The Company also provided an update on its pre-clinical and clinical development programs.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

"Our team continues its solid execution to drive forward the development across our clinical and preclinical programs. During the second quarter, we achieved key milestones across multiple fronts including bolstering our management team and scientific expertise, commencing our pivotal Phase 3 DETECT-trial of macimorelin, and advancing our earlier-stage preclinical development pipeline," commented Dr. Klaus Paulini, Chief Executive Officer of Aeterna. "I believe we are well-positioned to propel the Company forward with the goal of creating meaningful shareholder value."

Recent Highlights:

Engaged neuro-immunologist, Michael Levy, MD, PhD, Research Director of the Division of Neuroimmunology & Neuroinfectious Disease at Massachusetts General Hospital as a scientific consultant to support the development of the Company’s targeted, highly specific immunosuppressive therapeutic proteins ("AIM Biologicals") for the potential treatment of neuromyelitis optica spectrum disorder ("NMOSD").
Advanced preclinical development planning for potential orally active COVID-19 (SARS-CoV-2) live-attenuated bacterial vaccine program.
Initiated the preclinical program to qualify macimorelin for clinical development as a potential treatment option for amyotrophic lateral sclerosis (ALS; Lou Gehrig’s disease).
Commenced its pivotal Phase 3 safety and efficacy study AEZS-130-P02 ("the DETECT-trial") evaluating macimorelin for the diagnosis of childhood-onset growth hormone deficiency ("CGHD") in collaboration with Novo Nordisk.
In consultation with The University of Sheffield, UK, selected AEZS-150 as the lead candidate in the Company’s delayed clearance parathyroid hormone fusion polypeptides ("DC-PTH") program.
Appointed Michael Teifel, Ph.D. as Senior Vice President, Non-Clinical Development and Chief Scientific Officer.
Fully settled the previously disclosed class-action lawsuit against it in the U.S. District Court for the District of New Jersey, as approved by the U.S. District Court for the District of New Jersey.
All amounts in this press release are in U.S. dollars unless otherwise noted.

Preclinical and Clinical Programs Update:

Diagnostics Development Pipeline

Macimorelin Diagnostic:Ghrelin agonistin development for diagnostic use in childhood-onset growth hormone deficiency ("CGHD")

Aeterna Zentaris is currently conducting its pivotal Phase 3 safety and efficacy study AEZS-130-P02 ("the DETECT-trial") evaluating macimorelin for the diagnosis of CGHD. Children and adolescents from two to less than 18 years of age with suspected GHD are to be included. The study is expected to include approximately 100 subjects worldwide, with at least 40 subjects in pre-pubertal and 40 subjects in pubertal status. Macimorelin growth hormone stimulation test ("GHST") will be performed twice for repeatability data and two standard GHSTs will be used as controls: arginine (i.v.) and clonidine (p.o.). On April 22, 2021, the U.S. FDA Investigational New Drug Application associated with this clinical trial became active. The first clinical site in the U.S. is now open for patient recruitment.

Next Steps

Conduct and completion of the DETECT-trial.
Therapeutics and Vaccine Development Pipeline

AIM Biologicals:Targeted, highly specific autoimmunity modifying therapeutics for the potential treatment of neuromyelitisoptica spectrum disorder ("NMOSD")

In January 2021, Aeterna Zentaris entered into an exclusive patent license and research agreement with Julius-Maximilians-University of Wuerzburg, Germany for worldwide rights to develop, manufacture and commercialize AIM Biologicals for the potential treatment of NMOSD. The Company is currently conducting in-vitro and in-vivo assessments to identify and characterize an AIM Biologicals-based development candidate for the treatment of NMOSD and to develop a manufacturing process for the selected candidate. Additionally, the Company recently engaged neuro-immunologist, Dr. Michael Levy, who will provide scientific support and advice in the field of inflammatory CNS disorders, autoimmune diseases of the nervous system, and NMOSD.

Next Steps

Conduct further preclinical research to identify and characterize an AIM Biologicals-based development candidate for the treatment of NMOSD.
Manufacturing process development for selected candidate.
Macimorelin Therapeutic:Ghrelin agonist in developmentfor the treatment of ALS (Lou Gehrig’s disease)

In January 2021, the Company entered into a material transfer agreement ("MTA") with Queensland University, Australia, to provide macimorelin for the conduct of preclinical and subsequent clinical studies evaluating macimorelin as a potential therapeutic for the treatment of ALS (Lou Gehrig’s disease). Queensland University researchers have filed for supportive grants and aim to conduct preclinical studies in multiple models to demonstrate the therapeutic reach of macimorelin on disease progression and disease-specific pathology. They also plan to conduct a subsequent investigator initiated clinical trial given positive pre-clinical results.

Macimorelin, a ghrelin agonist, is an orally active small molecule that stimulates the secretion of growth hormone from the pituitary gland. Acting via this mechanism, it is believed that macimorelin may slow the progression of certain neurodegenerative diseases like ALS.

Next Steps

Work with Queensland University to conduct proof-of-concept studies with macimorelin in disease-specific animal models.
Assess alternative formulations.
Formalize preclinical development plan.
Delayed Clearance Parathyroid Hormone ("DC-PTH") Fusion Polypeptides:Potential treatment for primary hypoparathyroidism

In March 2021, Aeterna entered into an exclusive patent and know-how license agreement and research agreement with The University of Sheffield, United Kingdom, for the intellectual property relating to DC-PTH fusion polypeptides with delayed clearance covering the field of all human uses. In consultation with the University, Aeterna has selected AEZS-150 as the lead candidate in its delayed clearance parathyroid hormone fusion polypeptides ("DC-PTH") program. Aeterna will now start the formal preclinical development of AEZS-150 in preparation for a potential IND filing for conducting the first in-human clinical study of AEZS-150. AEZS-150 is being developed with the goal of providing a potential new treatment option of primary hypoparathyroidism in adults.

Next Steps

Work with The University of Sheffield to conduct in depth characterization of development candidate (in-vitro and in-vivo).
Develop manufacturing process.
Oral Coronavirus Vaccine Platform:Potential orally active COVID-19 (SARS-CoV-2) live-attenuated bacterial vaccine

In February 2021, Aeterna entered into an exclusive option agreement with Julius-Maximilians-University to evaluate a preclinical, potential COVID-19 vaccine developed at Julius-Maximilians-University. In March 2021, the Company exercised its option and entered into a license agreement where the Company was granted an exclusive, world-wide, license to certain patent applications and know-how owned by Julius-Maximilians-University to research and develop, manufacture, and sell a potential COVID-19 vaccine.

Julius-Maximilians-University also granted Aeterna an option for the exclusive use of certain patent applications and know-how in an additional, so-far undisclosed field. The Company has six months from the date of the license agreement to exercise that option. Additionally, Aeterna entered into a Research Agreement under which the Company has engaged Julius-Maximilians-University on a fee-for-service basis to conduct supplementary research work and preclinical development studies on the potential vaccine, the results of which will be included within the scope of the license agreement.

Next Steps

Conclude in-vivo immunology experiments with antigen variant vaccine candidates.
Perform challenge experiments in immunized transgenic animals as proof of concept.
Select a development candidate for initiation of the formal preclinical toxicology and safety studies.
Start manufacturing process assessment / development.
Financing and Warrant Exercises

During the period between January 1, 2021 and June 30, 2021, holders have exercised certain of the Company’s outstanding warrants to purchase 35,011,187 of the Company’s common shares for gross proceeds of approximately $20.0 million. The Company had $69.9 million cash and cash equivalents at June 30, 2021 (March 31, 2021 – 73.4 million).

Summary of Second Quarter 2021 Financial Results

Results of operations for the three-month period ended June 30, 2021

For the three-month period ended June 30, 2021, we reported a consolidated net loss of $2.0 million, or $0.02 loss per common share (basic), as compared with a consolidated net loss of $3.5 million, or $0.15 loss per common share (basic) for the three-month period ended June 30, 2020. The $1.5 million improvement in net loss is primarily from an increase in net finance income of $2.1 million and an increase of $0.5 million in total revenues, partially offset by an increase of $1.2 million in total operating expenses.

Revenues

Our total revenue for the three-month period ended June 30, 2021 was $0.60 million as compared with $0.07 million for the same period in 2020, representing an increase of $0.53 million. The 2021 revenue was comprised of $0.5 million in licensing revenue (2020 – $0.02 million), $0.04 million in supply chain revenue (2020 – $0.04 million) and $0.02 million in royalty income (2020 – $0.01 million). The licensing revenue was earned from the recognition of a portion of the deferred 5 million payment from Novo Nordisk received with the amendment to the Novo License agreement in the fourth quarter of 2020.
Operating expenses

Our total operating expenses for the three-month period ended June 30, 2021 was $2.7 million as compared with $1.5 million for the same period in 2020, representing an increase of $1.2 million. This increase arose primarily from a $0.5 million increase in research and development costs and $0.5 million increase in general and administrative expenses and an increase of $0.1 million in selling expenses. This increase in total operating expense is due to the initiation of research and development projects as announced in the first quarter of 2021, and higher public company costs incurred holding our annual shareholders meeting in May 2021, subsequent to our issuance of common shares in the February 2021 financing and the 2021 warrant exercises, in addition to higher auditor fees mostly related to F-3 warrant registration filings.
Net finance (costs) income

Our net finance income for the three-month period ended June 30, 2021 was $0.1 million as compared with net finance costs of ($2.0 million) for the same period in 2020, representing an increase in net finance income of $2.1 million. This is primarily due to the $2.1 million decrease in change in fair value of warrants. Unlike as at June 30, 2020, the Company did not account for its warrants as liabilities as at June 30, 2021. As at June 30, 2020, the fair value of such liabilities was classified as a finance cost in the consolidated statements of loss and comprehensive loss.
Consolidated Financial Statements and Management’s Discussion and Analysis

For reference, the Management’s Discussion and Analysis of Financial Condition and Results of Operations for the second quarter of 2021, as well as the Company’s unaudited consolidated interim financial statements as of June 30, 2021, will be available at www.zentaris.com in the Investors section or at the Company’s profile at www.sedar.com and www.sec.gov.

Purple Biotech Provides Corporate Update and Reports First Half 2021 Financial Results

On August 5, 2021 Purple Biotech Ltd. ("Purple Biotech", or the "Company") (NASDAQ/TASE: PPBT), a clinical-stage company developing first-in-class, effective and durable therapies by overcoming tumor immune evasion and drug resistance, reported financial results for the six months ended June 30, 2021 (Press release, Purple Biotech, AUG 5, 2021, View Source [SID1234585919]).

"We achieved significant progress in the advancement of our promising oncology pipeline during the first half of 2021," said Isaac Israel, Chief Executive Officer of Purple Biotech. "For NT219, we are currently treating patients in the third dose cohort of our ongoing Phase 1/2 clinical trial, and presented encouraging initial safety and efficacy results from this study at ASCO (Free ASCO Whitepaper). The initial results from the first dose level cohort demonstrated that NT219 was well-tolerated with minimal serious adverse events, and a partial response, including complete remission at the largest target lesion, was observed in one refractory patient previously treated with four lines of therapies. We expect to report additional data from higher dose levels of this study in the second half of this year. Moreover, for CM24, we are currently recruiting patients into the second dose cohort of our ongoing Phase 1b/2 clinical trial. There were no dose-limiting toxicities or serious clinically relevant adverse events observed in any patient enrolled in the first cohort of the study and we intend to provide additional preliminary safety and efficacy data at an upcoming medical conference."

"Importantly, our robust clinical development programs are supported by a strong balance sheet. With $53.4 million in cash, cash equivalent, short and long-term deposits at the end of June 2021, our cash runway extends into 2024," concluded Mr. Israel.

Recent Corporate Highlights

NT-219:

● Presented new data from the first dose level cohort of the ongoing Phase 1/2 clinical trial of NT219 at the 2021 the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. Initial results from the first dose level cohort showed that NT219 was well-tolerated with minimal serious adverse events. In addition, a partial response was observed in a patient with refractory gastroesophageal junction cancer, previously treated with four lines of therapies. In this patient, who had been treated for 22 weeks, a complete remission was seen at the largest target lesion and at one non-target lesion, while stable disease was observed at the other non-target lesion.

● Presented additional preclinical data supporting the mechanism of action of NT219 in a poster entitled, "Adaptation of colorectal cancer cells to the brain microenvironment: The role of IRS2," at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) 2021 Annual Meeting.

● Ongoing Phase 1/2 trial currently includes five active sites in the U.S, with others in the U.S. and Israel expected to be activated throughout the year.
CM24:

● Completed first dose level in Phase 1b/2 clinical trial of CM24, a monoclonal antibody blocking CEACAM1, in combination with nivolumab (Opdivo), a PD-1 inhibitor, in patients with advanced cancer, with expansion cohorts in subjects with non-small cell lung cancer and pancreatic cancer.

● The first dose level cohort demonstrated that CM24 in combination with nivolumab was well-tolerated with minimal serious adverse events.

● Currently recruiting patients into the second dose cohort of this study.

● Ongoing Phase 1b/2 trial currently includes three active sites in the U.S. and one in Israel, with others in the U.S., EU and Israel expected to be activated throughout the year.
CONSENSI:

● As previously disclosed, sales of Consensi in the U.S. have been adversely impacted by the ongoing COVID-19 pandemic. In addition, our U.S distribution partner has not fulfilled all its obligations as per the distribution agreement. The Company is currently evaluating its plans in order to maximize the value of Consensi.
Financial Results for the Six Months Ended June 30, 2021

No revenue was recorded for the six months ended June 30, 2021, as compared to $1.0 million for the same period of 2020.

Research and Development Expenses were $7.1 million, an increase of $4.0 million, or 129%, compared to $3.1 million in the same period of 2020. The increase was due to expenses related to the ongoing NT219 and CM24 clinical trials, including the manufacturing of drug for the studies.

Selling, General and Administrative (SG&A) Expenses were $3.2 million, compared to $2.2 million in the same period of 2020, an increase of $1 million. The increase was mainly due to a $0.6 million increase in ESOP costs and an increase in legal, consulting fees and insurance costs.

Operating Loss was $10.3 million, an increase of $6.0 million, or 139%, compared to $4.3 million in the same period of 2020.

On a non-IFRS basis (as reconciled below), adjusted operating loss was $8.9 million, an increase of $5.3 million, compared to $3.6 million in the same period of 2020, mainly due to the increased expenses for clinical studies and manufacturing of drug for these studies.

Net Loss for the first half of 2021 was $10.2 million, or $0.59 per diluted share, compared to a net loss of $27.8 million, or $4.63 per diluted share, in the first half of 2020. The decrease in net loss was due to $23.5 million in expenses related to a change in the fair value of derivatives, offset by an increase of $4.9 million in operating expenses and decrease of $1 million in revenues. Adjusted net loss for the first half was $8.8 million, an increase from $3.5 million in the first half of 2020.

As of June 30, 2021, Purple Biotech had cash and cash equivalents and short- and long-term deposits of $53.4 million, compared to $60.8 million on December 31, 2020. The Company believes that its cash position will provide sufficient resources to support its currently anticipated ongoing needs into 2024.

Madrigal Pharmaceuticals Reports 2021 Second Quarter Financial Results and Provides Corporate Update

On August 5, 2021 Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL) reported its second quarter 2021 financial results and provides a summary of corporate accomplishments.

Paul Friedman, M.D., Chief Executive Officer of Madrigal, stated, "The Madrigal team has made great progress on multiple fronts in the first half of 2021. Importantly, we reached our goal of enrollment to support the 52 week liver biopsy accelerated approval portion of MAESTRO-NASH. Top-line results are expected by the third quarter of 2022 for MAESTRO-NASH and by the end of this year for the non-invasive imaging and biomarker study, MAESTRO-NAFLD-1."

"We made multiple presentations recently at EASL. In particular, data from the open-label portion of the ongoing MAESTRO-NAFLD-1 Phase 3 clinical trial provide further evidence that treatment with resmetirom for 52 weeks leads to rapid and sustained reductions of liver fat, fibrosis, cell injury and inflammation in non-cirrhotic NASH patients that project favorably on the liver biopsy endpoints in MAESTRO-NASH," stated Becky Taub, M.D., Chief Medical Officer and President of Research & Development of Madrigal.

Dr. Taub added, "Also during the quarter, the Medical Affairs team at Madrigal continued to engage with the NASH physician and patient advocacy communities that recognize NASH with liver fibrosis as a very large unmet need. Our commercial team’s product launch planning also supports our objective to demonstrate the value of available non-invasive imaging and biomarkers that better diagnose and allow management of patients with NASH, enabling preparation for the planned launch and commercialization of resmetirom."

Recent Accomplishments
1. Clinical and Medical Affairs

Positive clinical results presented at the European Association for the Study of the Liver Annual Meeting (EASL), The International Liver Congress 2021, further point out the potential therapeutic value of resmetirom in a real-life NASH setting using non-invasive tools (versus serial liver biopsies): [click here to view press release]
Oral Plenary Presentation: Reduction in Fibrosis and Steatohepatitis Imaging and Biomarkers in a Phase 3, 52 Week Resmetirom NASH Trial. Presenter: Stephen Harrison [click here to view oral presentation]

EASL Poster: Treatment of NASH cirrhotic patients with resmetirom: baseline characteristics and effects on safety, biomarkers and imaging. Presenter: Stephen Harrison [click here to view poster]

Madrigal Hosted Symposium: Phase 3 development of resmetirom, a liver-directed thyroid hormone receptor (THR)-β agonist for the treatment of patients with NASH and significant liver fibrosis. Presenters: Vlad Ratziu, Jörn Schattenberg and Stephen Harrison [click here to view slides, click here to view webcast]

Analysis of patient reported outcome data from the Phase 2 trial of resmetirom revealed that achieving ≥30% relative reduction in hepatic fat was associated with greater improvements in Quality of Life Scores. Improvements in quality of life scores were also observed in those patients with NASH and fibrosis improvement on liver biopsy. The data has recently been published online in Clinical Gastroenterology and Hepatology: Hepatic Fat Reduction Due to Resmetirom in Patients with Nonalcoholic Steatohepatitis is Associated with Improvement of Quality of Life.

Well over 2,000 patients enrolled in MAESTRO trials that will help support the required safety database for NDA approval. Recent highlights:
Enrolled sufficient patients in the Phase 3 clinical trial MAESTRO-NASH to support the planned Subpart H (Accelerated Approval of New Drugs for Serious or Life-Threatening Illnesses) submission to the US Food and Drug Administration (FDA). Madrigal will continue to enroll additional patients beyond those required for accelerated approval to provide for the clinical outcomes portion of the MAESTRO-NASH Phase 3 clinical trial.

First patients enrolled in Phase 3 MAESTRO-NAFLD Open Label Extension Study (OLE). Patients who complete the first 52-week randomized portion of the study can receive 52 weeks of active treatment with resmetirom. The study is expected to provide both additional long-term safety and tolerability data as well as further efficacy measures documenting reduction of NASH using non-invasive scans and blood chemistries.

Medical Affairs Outreach:
Scientific engagements are occurring at NASH-focused meetings including: EASL, the American Association of Clinical Endocrinology (AACE), the American Association for the Study of Liver Diseases (AASLD), NASH-TAG, Paris-NASH, the GI Alliance and the Chronic Liver Disease Foundation (CLDF). These activities are intended to build awareness of the evolving clinical data supporting the therapeutic value of resmetirom, improve the medical community’s understanding of NASH, identify the unmet needs of NASH patients, and communicate the growing body of clinical evidence regarding the utility of non-invasive tools and techniques to diagnose and monitor NASH patients.
2. Launch and Commercial Preparation

In preparation for the planned U.S. launch of resmetirom, Madrigal is building its commercial resources and infrastructure, as well as developing a comprehensive product launch plan to position resmetirom for success. To date, our market research projects have involved over 1,000 hepatologists, gastroenterologists and endocrinologists as well as payers who together provide prescription coverage for the vast majority of the patients in the U.S. Results from these efforts confirm that (i) NASH patients with significant liver fibrosis (F2/F3) are already being non-invasively identified by physicians, but given the lack of approved treatment options they are looking for effective new medications to manage the disease; and, (ii) the majority of these physicians believe an ideal therapy for NASH patients with significant fibrosis which addresses the underlying pathophysiology of the disease in the liver will slow, halt and/or reverse disease progression.
3. Leadership Team Expanded

Alex Howarth, appointed Chief Financial Officer of Madrigal, adds important skills to Madrigal’s executive team and is responsible for the development of financial and corporate strategy, long-range planning, business development and implementation of financial and operational systems to support Madrigal’s continued growth and its transition to a commercial company.

Robert Waltermire, newly appointed as Chief Pharmaceutical Development Officer of Madrigal within Research and Development with responsibility for all aspects of chemistry, manufacturing and controls (CMC) and commercial product supply.
Financial Results
As of June 30, 2021, Madrigal had cash, cash equivalents and marketable securities of $323.8 million, compared to $284.1 million at December 31, 2020. The increase in cash and marketable securities was due to net proceeds of $130.2 million from sales of common stock via our at-the-market (ATM) program, partially offset by cash used to support operations of $90.3 million.

Operating expenses were $61.7 million and $114.7 million for the three and six month periods ended June 30, 2021, compared to $50.3 million and $88.3 million in the comparable prior year periods.

Research and development expenses for the three and six month periods ended June 30, 2021 were $51.6 million and $97.4 million, compared to $44.7 million and $78.1 million in the comparable prior year periods. The increase is attributable primarily to additional activities related to the Phase 3 clinical trials, and an increase in head count.

General and administrative expenses for the three and six month periods ended June 30, 2021 were $10.1 million and $17.3 million, compared to $5.6 million and $10.2 million in the comparable prior year periods. The increase is attributable primarily to increases in commercial preparation activities, including an increase in headcount, and an increase in non-cash stock compensation.

Interest income for the three and six month periods ended June 30, 2021 was $0.1 million and $0.3 million, compared to $1.2 million and $3.1 million in the comparable prior year periods. The decrease in interest income was due primarily to decreased interest rates.

About Resmetirom
Thyroid hormone, through activation of its β-receptor in hepatocytes, plays a central role in liver function impacting a range of health parameters from levels of serum cholesterol and triglycerides to the pathological buildup of fat in the liver. Thyroid hormone receptor (THR)-β action in the liver is key to proper function of the liver, including regulation of mitochondrial activity such as breakdown of liver fat and control of the level of normal, healthy mitochondria. Patients with NASH have reduced levels of thyroid hormone activity in the liver with resultant impaired hepatic function, in part due to the inflamed state of the liver that causes degradation of thyroid hormone.

To exploit the thyroid hormone receptor (THR)-β pathway for therapeutic purposes in cardio-metabolic and liver diseases, it is important to avoid activity at the THR-α receptor, the predominant systemic receptor for thyroid hormone that is responsible for activity outside the liver including in heart and bone. The lack of selectivity of older thyromimetic compounds, chemically-related toxicities and undesirable distribution in the body led to safety concerns. Madrigal recognized that greater selectivity for thyroid hormone receptor (THR)-β and liver targeting might overcome these challenges and deliver the full therapeutic potential of THR-β agonism. Resmetirom has been shown to be highly selective based on 1) THR-β receptor functional selectivity based on both in vitro and in vivo assays and 2) specific uptake into the liver, its site of action, virtually avoiding any uptake into tissues outside the liver. In short and long term human and animal studies, resmetirom has been confirmed to be safe and devoid of activity at the THR-α receptor and without impact on bone or cardiac parameters. Resmetirom does not impact the thyroid axis hormones, including the central thyroid axis. Madrigal believes that resmetirom is the first orally administered, small-molecule, liver-directed, truly β-selective THR agonist.

About the Phase 3 Registration Program for the Treatment of NASH (Non-alcoholic steatohepatitis)

Madrigal is currently conducting two Phase 3 Clinical trials, MAESTRO-NASH and MAESTRO-NAFLD-1, to demonstrate the safety and efficacy of resmetirom for the treatment of NASH.

MAESTRO-NASH is a Phase 3 multi-center, double-blind, randomized, placebo-controlled study of resmetirom in patients with liver biopsy confirmed NASH and was initiated in March 2019. The study targets enrollment of 900 patients with biopsy-proven NASH (fibrosis stage 2 or 3, at least 450 fibrosis stage 3), randomized 1:1:1 to receive resmetirom 80 mg once a day, 100 mg once a day, or placebo. After 52 weeks of treatment a second biopsy is performed. The primary surrogate endpoint on biopsy will be NASH resolution, with at least a 2-point reduction in NAS (NASH Activity Score), and with no worsening of fibrosis. Two key secondary endpoints are liver fibrosis reduction of at least one stage, with no worsening of NASH on liver biopsy, and lowering of LDL-cholesterol [ClinicalTrials.gov/NCT03900429]. Madrigal announced achievement of the planned target enrollment on June 30, 2021.

The first 900 patients in the MAESTRO-NASH study will continue on therapy after the initial 52-week treatment period; and up to another 1,100 patients are to be added using the same randomization plan and the study is expected to continue for up to 54 months to accrue and measure hepatic clinical outcome events including progression to cirrhosis on biopsy (52 weeks and 54 months) and hepatic decompensation events.

MAESTRO-NAFLD-1 is a 52-week Phase 3 multi-center, double-blind, randomized, placebo-controlled study of resmetirom, and was initiated in December 2019 in patients with non-alcoholic fatty liver disease (NAFLD), presumed NASH. The primary endpoint for this study is to evaluate the safety and tolerability of resmetirom. Completion of enrollment of over 1,200 patients into the study was announced in November 2020. Top-line data from the study is targeted by end of year 2021.

Patients in MAESTRO-NAFLD-1 are randomized 1:1:1 to receive resmetirom 80 mg once a day, 100 mg once a day, or placebo. MAESTRO-NAFLD-1 also includes a 100 mg resmetirom open label arm. 52 week data were presented from the open label arm at The International Liver Congress 2021 in June and demonstrated that resmetirom is safe and well-tolerated at 100mg per day [view press release here]. MAESTRO-NAFLD-1 (unlike MAESTRO-NASH), does not include a liver biopsy and represents a "real-life" NASH study. NASH or presumed NASH is documented using historical liver biopsy or non-invasive techniques including FibroScan and MRI-PDFF. Using non-invasive measures, MAESTRO-NAFLD-1 is designed to provide incremental safety information to support the NASH indication as well as provide additional data regarding clinically relevant key secondary efficacy endpoints to better characterize the potential clinical benefits of resmetirom on cardiovascular and liver related endpoints. These key secondary endpoints include LDL-cholesterol, apolipoprotein B and triglyceride (TG) lowering; reduction of liver fat as determined by magnetic resonance imaging, proton density fat fraction (MRI-PDFF); and reduction of PRO-C3, a NASH fibrosis biomarker. [ClinicalTrials.gov/NCT04197479]. Additional secondary and exploratory endpoints will be assessed including reduction in liver enzymes, FibroScan scores and other fibrosis and inflammatory biomarkers.

Data from the 52 week portion of MAESTRO-NASH, together with data from MAESTRO-NAFLD-1 and other data, including safety parameters, will form the basis for a potential subpart H submission to FDA for accelerated approval for the treatment of NASH

Portage Biotech Highlights First Patient Dosed in IMP-MEL Study of PORT-2 for the Treatment of Melanoma and Non-Small Cell Lung Cancer (NSCLC)

On August 5, 2021 Portage Biotech Inc., (NASDAQ: PRTG) ("Portage" or the "Company") a clinical-stage immuno-oncology company focused on the development of therapies targeting cancer treatment resistance, reported that the first patient has been dosed in the Oxford-led IMP-MEL study, a Phase 1/2, open-label, dose-escalation and randomized expansion clinical trial assessing the safety, tolerability and efficacy of PORT-2, a liposome formulation of the invariant natural killer T-cell (iNKT) agonist IMM60 developed for the treatment of solid tumors (Press release, Portage Biotech, AUG 5, 2021, View Source [SID1234585917]).

Preclinical data for PORT-2 demonstrated good tolerability and a strong cancer-specific B- and T-cell response. It also showed a robust innate and adaptive immune response and an increase in expression of PD-L1 on cancer cells. Combining PORT-2 with checkpoint inhibitors led to increased immune activation and PD-L1 expression, suggesting rationale for enhanced activity of the combination treatment.

"PORT-2 offers a novel, targeted approach to address a variety of today’s most common cancers, many of which are often elusive or resistant to treatment. Preclinical data show that our iNKT agonist can stimulate a broad response from both the innate and adaptive immune systems, helping the body recognize and attack these cancers," said Dr. Ian Walters, chief executive officer of Portage Biotech. "This first-in-human trial features a robust design with a multi-arm comparison against standard of care therapies currently used in the clinic, which we believe has the potential to accelerate our research as we evaluate the effectiveness of PORT-2 both as a monotherapy and in combination with PD-1 checkpoint inhibitors."

The IMP-MEL study is expected to enroll 100 patients at Oxford and other centers and will evaluate PORT-2 both as a monotherapy and in combination with approved PD-1 inhibitor Keytruda in the treatment of Melanoma and Non-Small Cell Lung Cancer (NSCLC).

"Checkpoint inhibitor therapies have enormous opportunity in the treatment of solid tumors, but unfortunately, many cancers develop a resistance to these therapies leaving many patients without adequate treatment options," said Mark Middleton, Departmental Head of Oncology and Professor of Experimental Medicine at the University of Oxford. "We’re constantly seeking new therapies that are capable of addressing resistance and enabling a durable response in patients with cancer. Should PORT-2 prove successful, this novel iNKT agonist therapy could potentially re-sensitize patients to checkpoint inhibitor treatment and could activate that durable immune response. It’s a very exciting new avenue for oncology research."

The IMP-MEL study is part of a comprehensive clinical development plan to evaluate Portage’s iNKT agonist therapies, PORT-2 and PORT-3. PORT-3, which is a nanoparticle co-formulation of IMM60 and a NY-ESO-1 peptide antigen, is also currently being evaluated in a Phase 1 clinical trial initiated in April 2021 at Radboud University, Netherlands.

The IMP-MEL study is supported by the NIHR Biomedical Research Centre. The trial is actively recruiting at the University of Oxford, United Kingdom. For more information, please visit View Source #ISRCTN80472712

About iNKT agonists PORT-2 and PORT-3

PORT-2 and PORT-3 contain small molecule agonists (IMM60) of invariant natural killer T-cells (iNKT cells) developed by the University of Oxford, which play an important role in anti-tumor immune responses. iNKT cells are a distinct class of T lymphocytes and recognize lipid antigens on the surface of the tumor. Our synthetic iNKT agonists are designed to optimally engage the T-cell receptor on the iNKT and facilitate its binding to dendritic cells, resulting in the secretion of a large amount of pro-inflammatory cytokines. This leads to the activation and expansion of important immune system components and primes and boosts an adaptive immune attack against cancer. We see that monotherapy treatment with iNKT agonists shows a heightened immune response and better cancer control in animal models that are resistant to PD-1 antibody treatment. Combination therapy with PD-1 antibodies is synergistic with iNKT agonists and restores sensitivity to PD-1 blockade. While treatment with iNKT agonists alone shows promising preclinical activity against cancer, data suggests that when an iNKT agonist is co-packaged with tumor-specific antigens, potency is increased by up to 5x. PORT-2 is a liposomal formulation of our IMM60 iNKT agonist while PORT-3 is a co-formulation of our IMM60 iNKT agonist with an NY-ESO-1 peptide vaccine, co-packaged into a nanoparticle.

Protara Therapeutics Announces Second Quarter 2021 Financial Results and Business Overview

On August 5, 2021 Protara Therapeutics, Inc. (Nasdaq: TARA), a clinical-stage company developing transformative therapies for the treatment of cancer and rare diseases with significant unmet needs, reported financial results for the second quarter ended June 30, 2021 and provided a business update (Press release, Protara Therapeutics, AUG 5, 2021, View Source [SID1234585916]).

"We continue to make significant progress executing against our development plans for TARA-002 in non-muscle invasive bladder cancer (NMIBC) and lymphatic malformations (LMs), and we look forward to achieving multiple important milestones in the second half of this year," said Jesse Shefferman, Chief Executive Officer of Protara Therapeutics. "With the successful completion of required non-clinical studies for TARA-002, we remain on track to submit our Investigational New Drug (IND) application and initiate our Phase 1 clinical study by year-end. In addition, our Good Manufacturing Practice (GMP) scale up and comparability work remain on track to be completed by year-end, and we look forward to working with the U.S. Food and Drug Administration (FDA) on a clinical trial of TARA-002 in patients with LMs, a rare pediatric indication for which there are currently no U.S. FDA-approved therapies."

Recent Highlights and Upcoming Milestones

TARA-002 Comparability

The Company remains on track to complete confirmatory, large-scale GMP manufacturing comparability by year-end.
TARA-002 in NMIBC

Protara successfully completed required non-clinical IND-enabling studies to characterize local toxicity of intravesical administration of TARA-002. The Company remains on track to submit an IND application in the second half of 2021 and, subject to the FDA acceptance of the IND application, the Company plans to commence a Phase 1 trial by the end of 2021 to assess the safety and tolerability of TARA-002 in patients with NMIBC, including patients with carcinoma in situ (CIS).
TARA-002 in LMs

Following the completion of confirmatory, large-scale GMP manufacturing comparability, the Company plans to align with the FDA on the design, and subsequently initiate a clinical trial in pediatric LM patients.
IV Choline Chloride in Intestinal Failure Associated Liver Disease (IFALD)

The Company is currently executing a prevalence study in partnership with a large home health organization in the U.S. to enhance understanding of the appropriate patient population and will use this information to define the next steps for the development program.
Corporate Update

In June 2021, the Company announced the appointment of Jane Huang, M.D., to its Board of Directors. Dr. Huang is an experienced biotech executive and proven leader throughout the development lifecycle of multiple oncology therapeutics globally and currently serves as Chief Medical Officer, Hematology at BeiGene, Ltd.
Second Quarter 2021 Financial Results

As of June 30, 2021, cash, cash equivalents and investments totaled $145 million.

Research and development expenses for the second quarter of 2021 increased to $5.9 million from $2.5 million during the second quarter of 2020. The increased R&D expenses were primarily due to increases in manufacturing and regulatory expenses associated with TARA-002.

General and administrative expenses for the second quarter of 2021 increased to $6.9 million from $4.8 million during the second quarter of 2020. The increase was primarily due to increases in stock-based compensation, headcount, and costs associated with the new Company headquarters in New York, NY.

For the second quarter of 2021, Protara reported a net loss of $12.8 million, or $1.14 per share, compared with a net loss of $7.1 million, or $1.22 per share, for the second quarter of 2020. Net loss for the second quarter of 2021 included approximately $3.0 million of stock-based compensation expenses.
About TARA-002

TARA-002 is an investigational cell therapy in development for the treatment of non-muscle invasive bladder cancer (NMIBC) and lymphatic malformations (LMs) for which it has been granted Rare Pediatric Disease Designation by the U.S. Food and Drug Administration. TARA-002 was developed from the same master cell bank of genetically distinct group A Streptococcus pyogenes as OK-432, a broad immunopotentiator marketed as Picibanil in Japan and Taiwan by Chugai Pharmaceutical Co., Ltd. Protara has successfully demonstrated initial manufacturing comparability between TARA-002 and OK-432.

When TARA-002 is administered, it is hypothesized that innate and adaptive immune cells within the cyst or tumor are activated and produce a strong immune cascade. Neutrophils, monocytes and lymphocytes infiltrate the abnormal cells and various cytokines, including interleukins IL-6, IL-8, IL-12, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and vascular endothelial growth factor (VEGF) are secreted by immune cells to induce a strong local inflammatory reaction and destroy the abnormal cells.

About Non-Muscle Invasive Bladder Cancer

Bladder cancer is the 6th most common cancer in the United States, with non-muscle invasive bladder cancer (NMIBC) representing approximately 80% of bladder cancer diagnoses. Approximately 65,000 patients are diagnosed with NMIBC in the United States each year. NMIBC is cancer found in the tissue that lines the inner surface of the bladder that has not spread into the bladder muscle.

About Lymphatic Malformations

Lymphatic malformations (LMs) are rare, congenital malformations of lymphatic vessels resulting in the failure of these structures to connect or drain into the venous system. Most LMs are present in the head and neck region and are diagnosed in early childhood during the period of active lymphatic growth, with more than 50% detected at birth and 90% diagnosed before the age of 3 years. The most common morbidities and serious manifestations of the disease include compression of the upper aerodigestive tract, including airway obstruction requiring intubation and possible tracheostomy dependence; intralesional bleeding; impingement on critical structures, including nerves, vessels, lymphatics; recurrent infection, and cosmetic and other functional disabilities.

About IV Choline Chloride and Intestinal Failure-associated Liver Disease (IFALD)

IV Choline Chloride is an investigational, intravenous (IV) phospholipid substrate replacement therapy initially in development for patients receiving parenteral nutrition (PN) who have IFALD. Choline is a known important substrate for phospholipids that are critical for healthy liver function. Because PN patients cannot sufficiently absorb adequate levels of choline and no available PN formulations contain sufficient amounts of choline to correct this deficiency, PN patients often experience a prolonged progression to hepatic failure and death, with the only known intervention being a dual small bowel/liver transplant. If approved, IV Choline Chloride would be the first approved therapy for IFALD. It has been granted Orphan Drug Designations (ODDs) by the FDA for the treatment of IFALD and the prevention of choline deficiency in PN patients.