On November 3, 2022 Cellectar Biosciences, Inc. (NASDAQ: CLRB), a late-stage biopharmaceutical company focused on the discovery, development and commercialization of targeted treatments for cancer, reported financial results for the third quarter ended September 30, 2022 and provided a corporate update (Press release, Cellectar Biosciences, NOV 3, 2022, View Source [SID1234623018]).

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Third Quarter and Recent Corporate Highlights

·In October, the company closed concurrent registered direct and private placement offerings totaling $10.7 million in gross proceeds with institutional investors including the company’s top three stockholders. The company sold 3,275,153 shares of the company’s common stock at $2.085 per share in the registered direct offering, while warrants to purchase up to an aggregate of 3,275,153 shares of common stock were sold in a concurrent private placement priced at-the-market under Nasdaq rules. In a separate concurrent private placement offering, the company sold institutional investors pre-funded warrants to purchase an aggregate of 1,875,945 shares of common stock and warrants to purchase an aggregate of 1,875,945 shares of common stock. The company intends to use the net proceeds from the registered direct offering and the private placements for funding clinical studies, research and development, working capital and general corporate purposes.

·Announced publication of data from the company’s expansion cohort of the Phase 2 CLOVER-1 Study of iopofosine in relapsed/refractory multiple myeloma in the September issue of Blood Cancer Journal, a peer-reviewed Nature journal. The paper, entitled "Iopofosine I-131 treatment in late-line patients with relapsed/refractory multiple myeloma post anti-BCMA immunotherapy," Initial patient data showed an overall response rate (ORR) of 50% in quad-class refractory multiple myeloma who have failed anti-BCMA Immunotherapy with a median of nine lines of therapy. The mean overall survival at the time of data cutoff was 9.1 months, with median overall survival not yet reached.

·Awarded $2 million grant to expand its ongoing Phase 1 study of iopofosine I 131 in pediatric brain tumors. The grant was awarded by the National Institute of Health’s National Cancer Institute (NCI) based upon initial signals of efficacy. The funding allows for an expansion from the Part 1a to the Part 1b portion of the company’s ongoing Phase 1 pediatric study. The ongoing Phase 1a is designed to determine the safety, tolerability, and initial efficacy of iopofosine in pediatric brain tumors whereas the Phase 1b is designed to identify the dose and dosing regimen that results in optimal efficacy. Previously announced preliminary data demonstrated therapeutic responses to iopofosine as evidenced by changes in multiple tumor parameters and patients experiencing extended progression free survival.

"Iopofosine continues to demonstrate its potential as a novel targeted radiotherapeutic in multiple ongoing trials in Waldenstrom’s macroglobulinemia (WM), multiple myeloma, CNS lymphoma, pediatric brain tumors and sarcomas. Additionally, we appreciate the recognition and additional grant from the NCI to support the expansion of our pediatric brain tumor trial into a Phase 1b based on demonstrated safety and activity," said James Caruso, president and CEO of Cellectar. "Our third quarter cash balance of $17.8 million, combined with the net proceeds from our successful October financing, provide the necessary capital to achieve several key milestones. We look forward to sharing topline data from our pivotal Phase 2b WM trial in the first half of 2023, and anticipate providing additional data from our phase 2a trial and our phase 1 pediatric trial in the near term."

Third Quarter 2022 Financial Highlights

·Cash and Cash Equivalents: As of September 30, 2022, the company had cash and cash equivalents of $17.8 million, compared to $35.7 million as of December 31, 2021. Net cash used in operating activities during the nine months ended September 30, 2022 was approximately $17.8 million. Subsequent to the end of the quarter, the Company raised $10.7 million in gross proceeds through a combined registered direct and PIPE offering. The company believes its cash on hand, inclusive of the October raise, is adequate to fund planned budgeted operations into the fourth quarter of 2023.

·Research and Development Expense: R&D expense for the three months ended September 30, 2022 was approximately $5.4 million, compared to approximately $3.9 million for the three months ended September 30, 2021. For the nine months ended September 30, 2022, R&D expense was approximately $13.8 million, while the comparable period in 2021 was $13.2 million. The increase for both the three- and nine-month periods was primarily a result of the timing of activities related to our ongoing WM pivotal trial.

·General and Administrative Expense: G&A expense for the three months ended September 30, 2022 was $2.4 million, compared to $1.9 million for the same period in 2021. G&A expense in the nine months ended September 30, 2022 was approximately $7.6 million, as compared to approximately $5.0 million in the prior year. These increases were driven largely by professional fees and personnel costs.

·Net Loss: The net loss attributable to common stockholders for the quarter ended September 30, 2022 was ($7.8) million, or ($1.28) per share, compared to ($5.8) million, or ($0.97) per share, in the quarter ended September 30, 2021, while the loss attributable to common stockholders for the nine months ended September 30, 2022 was ($21.4) million, or ($3.50) per share, compared to ($18.2) million, or ($3.39) per share, in 2021.

On November 3, 2022 BioMarin Pharmaceutical Inc. (NASDAQ: BMRN) reported that management will present at two upcoming investor conferences (Press release, BioMarin, NOV 3, 2022, View Source2022-11-03-BioMarin-to-Participate-in-Two-Upcoming-Investor-Conferences" target="_blank" title="View Source2022-11-03-BioMarin-to-Participate-in-Two-Upcoming-Investor-Conferences" rel="nofollow">View Source [SID1234623017]). To access the live webcasts, please visit: View Source . An archived version of the presentations will also be available through the Company’s website for a limited time following the conference.

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On November 3, 2022 Pacira BioSciences, Inc. (Nasdaq: PCRX), the industry leader in its commitment to non-opioid pain management and regenerative health solutions, reported financial results for the third quarter of 2022 (Press release, Pacira Pharmaceuticals, NOV 3, 2022, View Source;991.htm [SID1234623016]).

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Third Quarter 2022 Financial Highlights

Total revenues of $167.5 million
Net product sales of $132.6 million for EXPAREL, $26.5 million for ZILRETTA, and $4.5 million for iovera°
Net loss of $0.7 million, or $(0.02) per share (basic and diluted)
Adjusted EBITDA of $55.2 million
"In the third quarter, we continued to post increasing revenue and adjusted EBITDA, which underscores the success we are achieving in bringing our innovative non-opioid pain management solutions to patients," said Dave Stack, chairman and chief executive officer of Pacira BioSciences. "Moving forward, with an EXPAREL exclusivity runway extending into 2041 driving significant and durable operating cash flows, we are well-positioned to deliver near- and long-term value creation through a blend of new indications within our current commercial portfolio as well as new product development opportunities to support our growth in 2023 and beyond."

Recent Business Highlights

New EXPAREL Patent and Notice of Allowance. In October, the U.S. Patent and Trademark Office (USPTO) issued Patent Number 11,452,691. This patent is a chemical composition patent, with an expiration date of January 22, 2041. This patent is now listed in the U.S. Food and Drug Administration’s Approved Drug Products with Therapeutic Equivalents Evaluations (Orange Book) and is the 8th listed patent. The company also received a Notice of Allowance from the USPTO for a U.S. Patent Application that is a product by process patent for EXPAREL. After issuance, Pacira will submit this patent for listing in the Orange Book.

Positive Topline Data from Two Phase 3 Registration Studies of EXPAREL as a Lower Extremity Nerve Block. In September, the company announced positive topline results from two Phase 3 registration studies of EXPAREL as a single-dose nerve block for postsurgical regional analgesia in lower extremity surgeries. The first study evaluated EXPAREL as a femoral nerve block in the adductor canal for total knee arthroplasty and the second study evaluated EXPAREL as a sciatic nerve block in the popliteal fossa for bunionectomy. Both studies achieved statistical significance for the primary endpoint demonstrating a statistically significant reduction in cumulative pain scores from 0 to 96 hours (p<0.01) and the key secondary endpoint reduction in postsurgical opioid consumption through 96 hours (p<0.01) compared with bupivacaine HCl. In the bunionectomy study, EXPAREL also achieved statistical significance for the percentage of opioid-free subjects (p<0.001) through 96 hours compared with bupivacaine HCl. EXPAREL was well tolerated with a safety profile consistent with bupivacaine HCl.

Positive CHMP Opinion for EXPAREL for the Treatment of Postsurgical Pain in Children Aged 6 or Older. In September, the company announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending marketing authorization for an expanded indication of EXPAREL to include use in children aged 6 years and older as a field block for treatment of somatic post-operative pain from small- to medium-sized surgical wounds. The CHMP opinion was based on the results of the Phase 3 PLAY study of EXPAREL infiltration in pediatric patients undergoing spinal or cardiac surgeries. Overall findings were consistent with the pharmacokinetic and safety profiles for adult patients with no safety concerns identified at a dose of 4 mg/kg.

Positive Phase 1 Data for PCRX-201. The company recently finished analyzing data from its Phase 1 study of PCRX-201, a novel, intra-articular gene therapy product candidate that produces IL-1Ra for osteoarthritis. Based upon very compelling initial Phase 1 efficacy and safety data for PCRX-201, we are working with investigators and plan to request an FDA meeting to discuss the regulatory pathway forward for osteoarthritis of the knee—a very important and exciting addition to our durable non-opioid pain management pipeline.
Third Quarter 2022 Financial Results

Total revenues were $167.5 million in the third quarter of 2022, versus the $127.7 million reported for the third quarter of 2021.
EXPAREL net product sales were $132.6 million in the third quarter of 2022, versus the $121.9 million reported for the third quarter of 2021.
ZILRETTA net product sales were $26.5 million in the third quarter of 2022. The company began recognizing ZILRETTA sales upon completing its acquisition of Flexion Therapeutics, Inc. in November 2021.
Third quarter 2022 iovera° net product sales were $4.5 million, versus the $4.2 million reported for the third quarter of 2021.
Sales of bupivacaine liposome injectable suspension to a third-party licensee for use in veterinary practice were $3.0 million in the third quarter of 2022, versus the $0.7 million reported for the third quarter of 2021.
Third quarter royalty and collaborative licensing and milestone revenues were $0.9 million in both 2022 and 2021.
Total operating expenses were $146.2 million in the third quarter of 2022, versus the $96.3 million reported for the third quarter of 2021.
Research and development (R&D) expenses were $19.4 million in the third quarter of 2022, compared to $11.6 million in the third quarter of 2021. R&D expenses included $7.2 million and $4.7 million of product development and manufacturing capacity expansion costs in the third quarters of 2022 and 2021, respectively.
Selling, general and administrative (SG&A) expenses were $61.3 million in the third quarter of 2022, compared to $47.9 million in the third quarter of 2021.
GAAP net loss was $0.7 million, or $(0.02) per share (basic and diluted) in the third quarter of 2022, compared to GAAP net income of $17.7 million, or $0.40 per share (basic) and $0.39 per share (diluted), in the third quarter of 2021.
Non-GAAP net income was $29.9 million, or $0.65 per share (basic) and $0.64 per share (diluted) in the third quarter of 2022, compared to $32.5 million, or $0.73 per share (basic) and $0.72 per share (diluted), in the third quarter of 2021.
Adjusted EBITDA was $55.2 million in the third quarter of 2022, compared to $48.1 million in the third quarter of 2021.
Pacira ended the third quarter of 2022 with cash, cash equivalents and available-for-sale investments ("cash") of $346.1 million. Cash provided by operations was $42.7 million in the third quarter of 2022, compared to $60.3 million in the third quarter of 2021.
Pacira had 45.8 million basic and diluted weighted average shares of common stock outstanding in the third quarter of 2022.
See "Non-GAAP Financial Information" below.

Financial Guidance

Since early 2020, the company’s revenues have been impacted by COVID-19 and pandemic-related challenges that included the significant postponement or suspension in the scheduling of elective surgical procedures due to public health guidance and government directives. While the degree of impact has diminished during the course of the pandemic due to the introduction of vaccines and the lessening of elective surgery restrictions, certain pandemic-related operational challenges persist. It remains unclear how long it will take the elective surgery market to normalize or if restrictions on elective procedures will recur due to future COVID-19 variants or otherwise. Given the continued uncertainty around labor shortages, COVID-19 and the pace of recovery for the elective surgery market, the company is currently not providing revenue or gross margin guidance. To provide greater transparency, Pacira is reporting monthly intra-quarter unaudited net product sales for EXPAREL, ZILRETTA, and iovera° until it has gained enough visibility around the impacts of COVID-19. Pacira is also providing weekly EXPAREL utilization and elective surgery data within its investor presentation, which is accessible at investor.pacira.com

Today the company is reiterating its full-year 2022 operating expense guidance as follows:

Non-GAAP R&D expense of $75 million to $85 million; and
Non-GAAP SG&A expense of $220 million to $230 million.
Stock-based compensation of $47 million to $50 million.
See "Non-GAAP Financial Information" below.

Today’s Conference Call and Webcast Reminder

The Pacira management team will host a conference call to discuss the company’s financial results and recent developments today, Thursday, November 3, 2022, at 8:30 a.m. ET. For listeners who wish to participate in the question and answer session via telephone, please pre-register at investor.pacira.com/upcoming-events. All registrants will receive dial-in information and a PIN allowing them to access the live call. In addition, a live audio of the conference call will be available as a webcast. Interested parties can access the event through the "Events" page on the Pacira website at investor.pacira.com. For those unable to participate in the live call, a replay of the webcast will be available on the Pacira website for approximately two weeks following the call.

Non-GAAP Financial Information

This press release contains financial measures that do not comply with U.S. generally accepted accounting principles (GAAP), such as non-GAAP net income, non-GAAP net income per common share, non-GAAP weighted average common shares outstanding-diluted, non-GAAP cost of goods sold, non-GAAP research and development (R&D) expense, non-GAAP selling, general and administrative (SG&A) expense, and adjusted EBITDA (as defined below), because these non-GAAP financial measures exclude the impact of items that management believes affect comparability or underlying business trends.

These measures supplement the company’s financial results prepared in accordance with GAAP. Pacira management uses these measures to better analyze its financial results, estimate its future cost of goods sold, R&D expense and SG&A expense outlook for 2022 and to help make managerial decisions. In management’s opinion, these non-GAAP measures are useful to investors and other users of the Company’s financial statements by providing greater transparency into the operating performance of Pacira and its future outlook. Such measures should not be deemed to be an alternative to GAAP requirements or a measure of liquidity for Pacira. Non-GAAP measures are also unlikely to be comparable with non-GAAP disclosures released by other companies. See the tables below for a reconciliation of GAAP to non-GAAP measures.

On November 3, 2022 Akoya Biosciences, Inc. (Nasdaq: AKYA) ("Akoya"), The Spatial Biology Company, reported that it will be participating in three upcoming investor conferences (Press release, Akoya Biosciences, NOV 3, 2022, View Source [SID1234623015]).

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Stephens Annual Investment Conference (Nashville, TN)
Fireside Chat on Wednesday, November 16th at 2:00 PM CT
Canaccord Genuity Annual MedTech, Diagnostics and Digital Health & Services Forum (New York, NY)
Multi-omics Panel on Thursday, November 17th at 1:00 PM ET
Piper-Sandler Annual Healthcare Conference (New York, NY)
Fireside Chat on Thursday, December 1st at 11:30 AM ET
Live and archived webcasts of the events will be available on the "Investors" section of the Akoya website at View Source

On November 3, 2022 Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL), a clinical-stage biopharmaceutical company pursuing novel therapeutics for nonalcoholic steatohepatitis (NASH), reported an overview of upcoming resmetirom Phase 3 data presentations and reports third quarter 2022 financial results (Press release, Synta Pharmaceuticals, NOV 3, 2022, View Source [SID1234623014]).

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Paul Friedman, M.D., Chief Executive Officer of Madrigal, stated, "The Madrigal team is focused on delivering topline data from the pivotal MAESTRO-NASH biopsy study in Q4 2022. Positive results from the study would allow us to finalize our new drug application for resmetirom, with the goal of filing for Subpart H accelerated approval in the first half of 2023. The efficacy and safety data we are generating across four Phase 3 MAESTRO studies put Madrigal in a strong position to navigate this accelerated approval pathway and potentially address the unmet needs of patients who currently have no approved therapy to treat NASH with significant fibrosis."

Becky Taub, M.D., Chief Medical Officer and President of Research & Development of Madrigal, stated, "The MAESTRO program continues to generate data that reinforce our conviction in the potential of resmetirom to become a foundational therapy for patients with NASH. At the upcoming American Association for the Study of Liver Diseases (AASLD) Liver Meeting, we’ll be presenting results from the compensated NASH cirrhosis cohort studied in MAESTRO-NAFLD-1. The safety and efficacy data in this more advanced patient population helped support our decision to initiate the Phase 3 MAESTRO-NASH Outcomes study, a noninvasive clinical endpoint study that assesses the rate of progression from early well-compensated NASH cirrhosis to decompensated NASH cirrhosis."

Dr. Taub continued, "A second oral presentation at AASLD will examine the ability of several noninvasive strategies to identify NASH patients with significant liver fibrosis using screening data from the MAESTRO-NASH biopsy study. Given the comprehensive diagnostic strategies included in MAESTRO studies, Madrigal has a unique opportunity to define noninvasive measures to diagnose and manage patients with NASH in real world clinical practice."

Presentations at the AASLD Liver Meeting

The following abstracts have been accepted for presentation at the AASLD Liver Meeting, taking place November 4-8 in Washington, DC:

Oral Presentation (abstract 100): Sunday, November 6th

A 52-week Phase 3 clinical trial of resmetirom in 180 patients with well-compensated NASH cirrhosis. Presenter: Stephen Harrison

In patients with well-compensated cirrhosis included in an open-label active resmetirom treatment arm of the Phase 3 MAESTRO-NAFLD-1 safety study, resmetirom lowered markers of cardiovascular risk and NASH fibrosis. Following 52 weeks of treatment with resmetirom, patients achieved reductions in magnetic resonance imaging proton density fat fraction (MRI-PDFF), FibroScan controlled attenuation parameter (CAP), FibroScan vibration-controlled transient elastography (VCTE), magnetic resonance elastography (MRE), liver and spleen volume, ALT, AST, GGT, LDL-C, triglycerides, ApoB, and lipoprotein (a). Resmetirom appeared safe and was well-tolerated during 52 weeks of treatment.

Oral Presentation (abstract 102): Sunday, November 6th

Utility of FIB-4, MRE, MRI and FibroScan to identify patients with at-risk F2-F3 NASH based on screening data from a 2000 patient biopsy confirmed cohort of the resmetirom Phase 3 clinical trial, MAESTRO-NASH. Presenter: Rohit Loomba

FIB-4 of ≥1.3 is frequently used to identify potential at-risk patients with NASH, but an analysis of screening data from the MAESTRO-NASH biopsy study found this threshold lacked the sensitivity to accurately identify patients with NASH with significant fibrosis (F2-F3). The authors concluded the influence of age on FIB-4 may require an age adjustment to ensure younger patients are not removed from consideration for therapy. MRE, MAST (MRI-AST) and FAST (FibroScan-AST) showed reasonable accuracy for identifying patients with NASH with significant fibrosis.

Financial Results for the Nine Months Ended September 30, 2022

As of September 30, 2022, Madrigal had cash, cash equivalents and marketable securities of $153.2 million, compared to $270.3 million at December 31, 2021. This decrease in cash and marketable securities resulted primarily from cash used in operations for the nine months ended September 30, 2022 of $166.3 million, partially offset by the net proceeds ($49 million) from the Loan Facility ("Loan Facility") with Hercules Capital, Inc. ("Hercules").

Operating expenses were $80.4 million and $208.3 million for the three month and nine month periods ended September 30, 2022, compared to $63.2 million and $177.9 million in the comparable prior year periods.

Research and development expenses for the three and nine month periods ended September 30, 2022 were $68.3 million and $174.7 million, compared to $54.9 million and $152.3 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 nine month periods ended September 30, 2022 were $12.1 million and $33.6 million, compared to $8.3 million and $25.6 million in the comparable prior year periods. The increase is due 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 nine month periods ended September 30, 2022 was $0.7 million and $1.1 million, compared to $0.1 million and $0.3 million in the comparable prior year periods. These increases in interest income were due primarily to higher average interest rates in 2022.

Interest expense for the three and nine month periods ended September 30, 2022 was $1.5 million and $2.3 million, compared to $0 million and $0 million in the comparable prior year periods. The increase in interest expense was as a result of the Loan Facility with Hercules, which we closed in May of 2022.

About the Resmetirom Phase 3 Registration Program for the Treatment of NASH

Madrigal is currently conducting four Phase 3 clinical trials to demonstrate the safety and efficacy of resmetirom for the treatment of NASH: MAESTRO-NASH, MAESTRO-NAFLD-1, MAESTRO-NAFLD-OLE, and MAESTRO-NASH Outcomes.

MAESTRO-NASH is a multicenter, randomized, double-blind, placebo-controlled Phase 3 study of resmetirom in patients with liver biopsy-confirmed NASH and was initiated in March 2019. The study enrolled more than 1,000 patients with biopsy-proven NASH (at least half with F3 (advanced) fibrosis, the remainder F2 or F1B (moderate fibrosis, with a few earlier F1 patients), randomized 1:1:1 to receive once-daily resmetirom 80 mg, resmetirom 100 mg, or placebo. After 52 weeks of treatment, a second biopsy is performed. The dual primary surrogate endpoints on biopsy are NASH resolution with ≥2-point reduction in NAS (NAFLD Activity Score), and with no worsening of fibrosis OR a 1-point decrease in fibrosis with no worsening of NASH. Achievement of either primary endpoint is considered a successful trial outcome. A key secondary endpoint is lowering of LDL-C. The planned target enrollment was announced as completed on June 30, 2021.

All patients enrolled in the MAESTRO-NASH study (up to 2,000 in total) continue on therapy after the initial 52-week treatment period 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 was initiated in December 2019 and the 52-week multicenter, randomized, placebo-controlled Phase 3 study of resmetirom in over 1,200 patients with NAFLD, presumed

NASH, has completed the double-blind arms and an open-label 100 mg arm. An additional open-label active treatment arm in patients with early (well-compensated) NASH cirrhosis is ongoing. The primary endpoint was to evaluate the safety and tolerability of resmetirom. A separate 52-week Phase 3 clinical trial, an open-label extension study of MAESTRO-NAFLD-1 (MAESTRO-NAFLD-OLE) is ongoing.

Patients in the 52-week Phase 3 MAESTRO-NAFLD-1 study were randomized 1:1:1:1 to receive once-daily resmetirom 80 mg, resmetirom 100 mg, placebo in double-blind arms, or resmetirom 100 mg in an open-label arm. MAESTRO-NAFLD-1 (unlike MAESTRO-NASH) did not include a liver biopsy and represents a "real-life" NASH study. Patients with 3 metabolic risk factors were documented with NASH or NAFLD by historical liver biopsy or noninvasive techniques. Using noninvasive measures, MAESTRO-NAFLD-1 was 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. The primary safety endpoint and several key secondary endpoints were met, including LDL-C, apolipoprotein B, and triglyceride lowering and reduction of liver fat as determined by MRI-PDFF. Additional secondary and exploratory endpoints were assessed, including reduction in liver enzymes, FibroScan, and MRE scores, and other NASH biomarkers.

Data from the 52-week first 1,000 patient 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 of resmetirom for treatment of NASH.

In August 2022, Madrigal initiated MAESTRO-NASH Outcomes, a randomized double-blind placebo-controlled study in approximately 700 patients with early NASH cirrhosis to allow for noninvasive monitoring of progression to liver decompensation events. A positive outcome is expected to support the full approval of resmetirom for noncirrhotic NASH, potentially accelerating the timeline to full approval. In addition, this study has the potential to support an additional indication for resmetirom in patients with well-compensated NASH cirrhosis.