On May 9, 2022 BioXcel Therapeutics, Inc. (Nasdaq: BTAI), a commercial-stage biopharmaceutical company utilizing artificial intelligence approaches to develop transformative medicines in neuroscience and immuno-oncology, reported its financial results for the first quarter ended March 31, 2022 and provided an update on key strategic initiatives (Press release, BioXcel, MAY 9, 2022, View Source [SID1234613879]).

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"2022 has already been a transformative year during which we have made monumental progress on our journey to become the leading AI-enabled neuroscience company. Our recent achievements across our clinical, business, and commercial priorities, highlighted by our first FDA approval of IGALMI, have positioned us to realize our 2022 goals and beyond," said Vimal Mehta, Ph.D., CEO of BioXcel Therapeutics. "Building on this momentum, we are excited to launch IGALMI, advance our proven technology, and continue delivering innovative medicines to patients and caregivers."

Company Highlights

Neuroscience Franchise

IGALMI Approval and Commercial Launch

IGALMI was approved by the FDA on April 5, 2022 for the acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults.1 Within these two patient populations in the U.S., up to 25 million agitation episodes occur each year.2-4

The Company is focused on the following key commercial launch activities to provide access to patients and caregivers:

·Institutional Sales Force: Seasoned sales specialists were onboarded, undergoing training, and will be deployed for launch. The team has an average of over 21 years of industry experience, 14 years in hospital settings, and 8 product launches.
oLaunch meeting to be held in mid-May in preparation for national salesforce deployment on May 23rd across priority regions and customers.
·Market Access Team: Currently engaging with group purchasing organizations (GPOs) and high value Integrated Delivery Networks (IDNs).
·Trade Launch: Product load into distribution channels in Q3 2022.

Clinical Pipeline

BXCL501, a proprietary, sublingual film formulation of dexmedetomidine, is being investigated in multiple neuropsychiatric conditions. BXCL501 has received Breakthrough Therapy and Fast Track designation for the acute treatment of agitation associated with dementia.

Indication Expansion

·Alzheimer’s Disease-related Agitation: TRANQUILITY program designed to maximize BXCL501 opportunity to treat Alzheimer’s Disease-related agitation. There are an estimated 100 million agitation episodes in Alzheimer’s patients occurring in the U.S. annually.5
oTRANQUILITY II: First patient dosed; top-line data readout in Q4 2022/early Q1 2023.
oTRANQUILITY III: Trial underway with enrollment initiating in 2H 2022.
oSelection of 40 mcg and 60 mcg dosing regimens in pivotal trial supported by breakthrough designation from the FDA, along with positive efficacy, safety, and tolerability data observed in 100 patients in the Phase 1b/2 TRANQUILITY trial and a recent study of BXCL501 40 mcg.

·Adjunctive Treatment for Major Depressive Disorder (MDD): Initiated Phase 1 multiple ascending dose trial in healthy volunteers.

Geographic Expansion

·Marketing Authorization Application: Submission to the European Medicines Agency (EMA) for BXCL501 for acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults in 2Q 2022.
·Japan Entry: Company exploring market entry strategies to expand access of IGALMI to patients in Japan.

OnkosXcel Therapeutics

Established OnkosXcel Therapeutics as a wholly owned subsidiary to focus on the sustained expansion and optimization of the Company’s immuno-oncology (I-O) franchise, including its most advanced I-O program, BXCL701. BXCL701 is an investigational, orally administered, systemic innate immune activator in development for the treatment of aggressive forms of prostate cancer and advanced solid tumors that are refractory or treatment naïve to checkpoint inhibitors.

·Metastatic Castration-Resistant Prostate Cancer (mCRPC) Program: Following positive Phase 2 data for BXCL701 in combination with KEYTRUDA (pembrolizumab) announced this past February, continued ongoing Phase 2 trial in mCRPC patients with either small cell neuroendocrine carcinoma (SCNC) or adenocarcinoma phenotype.
oExpect to complete enrollment of 28-patient SCNC cohort in 2H 2022.
oFirst patient enrolled in adenocarcinoma randomized trial expansion evaluating BXCL701 monotherapy vs. BXCL701-KEYTRUDA combination therapy.

·Solid Tumors Program (Checkpoint Naïve and Refractory): Additional efficacy data from MD Anderson-led open-label Phase 2 basket trial of BXCL701 and KEYTRUDA is expected in 2H 2022.

Strategic Financing

·Announced $260 Million Strategic Financing with Oaktree and Qatar Investment Authority: Full execution of this financing would extend the Company’s cash runway into 2025 to support the commercial launch of IGALMI and achieve key clinical and regulatory milestones.

First Quarter 2022 Financial Results

Research and Development Expenses: Research and development expenses were $18.6 million for the first quarter of 2022, compared to $14.7 million for the same period in 2021. The increased expenses were primarily attributable to clinical trial costs related to the Company’s TRANQUILITY program.

General and Administrative Expenses: General and administrative expenses were $12.9 million for the first quarter of 2022, as compared to $11.6 million for the same period in 2021. The increase was primarily due to personnel and costs related to the commercial launch readiness efforts for IGALMI in the U.S.

Net Loss: BioXcel Therapeutics reported a net loss of $31.5 million for the first quarter of 2022, compared to a net loss of $26.4 million for the same period in 2021.

As of March 31, 2022, cash and cash equivalents totaled approximately $200 million. This excludes contributions from the $260 million strategic financing announced in April. To date the Company has drawn $70M of the loan agreement and has met the milestone to receive $30M of the royalty financing which is expected to be drawn in the second quarter of 2022.

Conference Call

BioXcel Therapeutics will host a conference call and webcast May 9, 2022, at 8:30 a.m., ET, to discuss its first quarter 2022 financial results and provide an update on recent operational highlights. To access the call, please dial 877-407-5795 (domestic) and 201-689-8722 (international). A live webcast of the call will be available on the Investors section of the BioXcel website, www.bioxceltherapeutics.com, and a replay of the call will be available through August 9, 2022.

BioXcel Therapeutics may use its website as a distribution channel of material information about the Company. Financial and other important information regarding the Company is routinely posted on and accessible through the Investors sections of its website at www.bioxceltherapeutics.com. In addition, you may automatically receive email alerts and other information about the Company when you enroll your email address by visiting the "Email Alerts" option under the News/Events menu of the Investors & Media section of its website.

About TRANQUILITY II and III

Initiated in December of 2021, TRANQUILITY II and III are pivotal Phase 3 trials evaluating BXCL501 for the acute treatment of agitation in patients with Alzheimer’s disease. The trials expand the evaluation of patients who experience agitation across diverse medical settings and across the range of dementia severity. TRANQUILITY II and III are designed to maximize the opportunity of BXCL501 for the treatment of the full spectrum of agitation associated with AD. Each trial will enroll approximately 150 dementia patients 65 years and older who will self-administer 40 mcg or 60 mcg of BXCL501 or placebo whenever agitation episodes occur over a three-month period. TRANQUILITY II will assess patients in assisted living or residential facilities requiring minimal assistance with activities of daily living. TRANQUILITY III will assess patients residing in nursing homes with moderate to severe dementia and require moderate or greater assistance with activities of daily living. The studies will assess agitation as measured by the changes from baseline in the Positive and Negative Syndrome Scale-Excitatory Component (PEC) and Pittsburgh Agitation Scale (PAS) total scores. The primary efficacy endpoint for both studies is change in PEC score from baseline measured at two hours after the initial dose and subsequent doses.

On May 9, 2022 Surface Oncology (Nasdaq: SURF), a clinical-stage immuno-oncology company developing next-generation immunotherapies that target the tumor microenvironment, reported financial results and corporate highlights for the first quarter of 2022 as well as upcoming anticipated corporate milestones.

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"The first quarter of 2022 marked the beginning of a data-rich year for Surface, starting with the presentation of preclinical and translational SRF388 data at AACR (Free AACR Whitepaper) in April," said Rob Ross, M.D., chief executive officer. "We are actively developing two novel antibodies in Phase 2 studies, SRF388 and SRF617, and our runway now provides us with 12 months of cash beyond data readouts for up to six different indications and combination studies across the programs. We look forward to presenting our next update on SRF388, the only antibody targeting IL-27 in the clinic, at ASCO (Free ASCO Whitepaper), and we remain on track to share new clinical data for SRF617 in the second half of this year."

First Quarter and Subsequent Corporate Highlights

During the first quarter, Surface raised net proceeds of approximately $21 million through the company’s existing At-the-Market (ATM) facility with participation based on unsolicited interest received from EcoR1 and Octagon Capital Advisors.

At the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022, Surface presented SRF388 preclinical and translational data supporting the recommended Phase 2 monotherapy dose selection of 10 mg/kg administered intravenously every four weeks. This dose is being studied in dedicated expansion cohorts of treatment-refractory clear cell renal cell carcinoma (ccRCC), non-small-cell lung cancer (NSCLC), and hepatocellular carcinoma (HCC).

In March, Surface announced that the first patient had been dosed by GlaxoSmithKline (GSK) in a Phase 1 study evaluating GSK4381562 in patients with solid tumors. GSK4381562 is a fully human IgG1 antibody targeting PVRIG, an inhibitory protein on the TIGIT/DNAM/TACTILE axis that is expressed on natural killer cells (NK cells) and T cells. As a result, Surface is entitled to a $30 million milestone payment and is eligible to receive an additional $700 million in potential future milestone payments, and tiered royalties on global net sales.

In March, the company announced the appointment of Theresa Boni, J.D., as general counsel and senior vice president, legal. Ms. Boni brings more than 20 years of legal experience spanning the biopharmaceutical and medical device industries.
SRF388 Clinical Trial Progress and Updates

In April 2022, Surface announced the initiation of two Phase 2 clinical studies evaluating SRF388, a potential first-in-class antibody against IL-27. The initiations include the first patient dosed in a Phase 2 monotherapy clinical study in treatment-refractory NSCLC patients and the first patient dosed in the lead-in to a randomized Phase 2 clinical study in combination with atezolizumab and bevacizumab in patients with HCC who have not received prior systemic treatment (first-line).

With respect to the design of the SRF388 randomized Phase 2 study in first-line HCC, the company will expand the open-label lead-in from six patients, as originally planned, to approximately 30 patients. Management believes this expanded lead-in will provide more robust safety and efficacy data to inform the start of the randomized stage and could elucidate important biomarkers to support enriched patient selection. Data from the lead-in are anticipated in the first half of 2023.

New clinical data on SRF388 will be presented in an oral session at the 2022 ASCO (Free ASCO Whitepaper) Annual Meeting. The session, entitled "First-in-human study of SRF388, a first-in-class IL-27 targeting antibody, as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors," will be held Saturday, June 4, 2022, from 1:15 pm – 4:15 pm CDT.
Selected Anticipated Near-term Corporate Milestones

The company remains on track to provide a clinical data update on SRF617, a fully human antibody designed to inhibit CD39, in the second half of 2022.

Surface anticipates filing an Investigational New Drug application for SRF114, a fully human IgG1 anti-CCR8 antibody, in the second half of 2022.
Financial Results
As of March 31, 2022, cash, cash equivalents and marketable securities were $150.4 million, compared to $154.1 million on December 31, 2021.

General and administrative (G&A) expenses were $6.5 million for the first quarter ended March 31, 2022, compared to $5.6 million for the same period in 2021. This increase was primarily due to increases in personnel and facility-related costs and increased insurance premiums. G&A expenses included $1.3 million in stock-based compensation expense for the first quarter ended March 31, 2022.

Research and development (R&D) expenses were $16.6 million for the first quarter ended March 31, 2022, compared to $10.5 million for the same period in 2021. This increase was primarily driven by progress on our SRF617 and SRF388 Phase 1 clinical trials and advancement into Phase 2 trials. R&D expenses included $0.6 million in stock-based compensation expense for the first quarter ended March 31, 2022.

For the first quarter ended March 31, 2022, net income was $6.2 million, or basic net income per share of $0.13 and diluted net income per share of $0.13. Net loss was $15.6 million for the same period in 2021, or basic and diluted net loss per share of $0.37.

Based upon the current operating plan, Surface projects its cash runway extending into 2024.

On May 9, 2022 HOOKIPA Pharma Inc. (NASDAQ: HOOK, ‘HOOKIPA’), a company developing a new class of immunotherapeutics based on its proprietary arenavirus platform, reported that it will release first quarter 2022 financial results before the market open on Monday, May 16, 2022 (Press release, Hookipa Pharma, MAY 9, 2022, View Source [SID1234613877]).

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The Company will not be conducting a conference call in conjunction with this earnings release.

On May 9, 2022 Eagle Pharmaceuticals, Inc. (Nasdaq: EGRX) ("Eagle" or the "Company") reported financial results for the three months ended March 31, 2022 (Press release, Eagle Pharmaceuticals, MAY 9, 2022, View Source [SID1234613876]).

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Business and Recent Highlights:

Achieved first quarter 2022 sales of $34.3 million for vasopressin, an A-rated generic alternative to Vasostrict, which the Company began shipping on January 18, 2022, with 180 days of marketing exclusivity. U.S. sales of Vasostrict totaled $901.7 million for the 12 months ended December 31, 2021, as reported by Endo International plc.
Achieved first quarter 2022 sales of $37.2 million of PEMFEXY (pemetrexed for injection), a branded alternative to ALIMTA. PEMFEXY is a ready-to-use liquid with a unique J-code and is approved in the U.S. to treat nonsquamous non-small cell lung cancer and mesothelioma. The ALIMTA U.S. market totaled $1.2 billion for the 12 months ended December 31, 2021, as reported by Eli Lilly and Company.
As previously announced, reached agreement on the proposed terms of a transfer of the entire issued and to be issued share capital of Acacia Pharma Group plc ("Acacia") to Eagle. The transaction is expected to close in June 2022, subject to satisfaction of closing conditions. The proposed transaction is expected to provide Eagle with two currently marketed, acute care, hospital products, both of which are new chemical entities ("NCEs") with strong patent protection:
BARHEMSYS, the first and only antiemetic approved by the FDA for rescue treatment of postoperative nausea and vomiting, and
BYFAVO1 indicated for the induction and maintenance of procedural sedation in adults undergoing procedures lasting 30 minutes or less.
Remains on track to support NDA filing by AOP Health Group ("AOP Health"), with whom Eagle entered into a licensing agreement in August 2021, for landiolol, a beta-1 adrenergic blocker, later this month.
Expects to start phase 2b/3 clinical trial in CAL02 patients in Q3 2022 during pneumonia season.
Reached a settlement agreement with Hospira, Inc., related to BENDEKA (bendamustine hydrochloride). Eagle had asserted two Orange Book-listed patents against Hospira related to its NDA referencing BENDEKA. The settlement agreement provides that Hospira has the right to market its product beginning January 17, 2028, or earlier based on certain circumstances.
Anticipates strong growth for 2022; key objective to pursue additional potential transactions to continue diversifying its commercial product portfolio and pipeline.
Financial Highlights

First Quarter 2022

Total revenue for Q1 2022 was $115.9 million, compared to $41.2 million in Q1 2021, primarily reflecting strong product sales of vasopressin and PEMFEXY.
Q1 2022 net income was $44.1 million, or $3.47 per basic and $3.41 per diluted share, compared to net loss of $0.4 million, or $0.03 per basic and diluted share, in Q1 2021.
Q1 2022 adjusted non-GAAP net income* was $52.2 million, or $4.10 per basic and $4.04 per diluted share, compared to adjusted non-GAAP net income of $3.2 million, or $0.24 per basic and diluted share, in Q1 2021.
Cash and cash equivalents were $69.5 million, net accounts receivable was $130.9 million, and debt was $24.0 million as of March 31, 2022. The Company had considerable cash outlays for the launch of vasopressin and PEMFEXY and repurchased $8.1 million of the Company stock in Q1 2022.
"The early momentum we saw at the beginning of 2022 has continued to build. We posted a great first quarter, reflecting the strong initial sales of vasopressin and PEMFEXY. We continue to strengthen our cash position, expect to acquire a company with two commercial assets, and significantly diversify our product portfolio," stated Scott Tarriff, President and Chief Executive Officer of Eagle Pharmaceuticals. "Looking ahead, we plan to put our cash and balance sheet to good use as we seek to further broaden our product offerings and pipeline and to expand our presence in the acute care and oncology spaces through potential acquisitions or licensing deals," concluded Tarriff.

First Quarter 2022 Financial Results

Total revenue for the three months ended March 31, 2022, was $115.9 million, as compared to $41.2 million for the three months ended March 31, 2021. A summary of total revenue by product is outlined below:

Gross margin was 76% during the first quarter of 2022, as compared to 74% in the first quarter of 2021. The increase in gross margin for the first quarter of 2022 was driven by the benefit of launch costs recognized in prior periods.

R&D expense was $6.1 million for the first quarter of 2022, compared to $14.3 million for the first quarter of 2021. The decrease was primarily due to the non-recurrence of development cost on vasopressin and lower spend on fulvestrant and RYANODEX related projects. Excluding stock-based compensation and other non-cash and non-recurring items, adjusted non-GAAP R&D expense* during the first quarter of 2022 was $5.4 million.

SG&A expenses in the first quarter of 2022 totaled $22.2 million compared to $19.9 million in the first quarter of 2021. This increase was primarily related to external legal spend for the anticipated acquisition of Acacia and sales and marketing costs for the launch of PEMFEXY partially offset by a decrease in stock-based compensation expense. Excluding stock-based compensation and other non-cash and non-recurring items, first quarter 2022 adjusted non-GAAP SG&A expense* was $16.6 million.

Net income for the first quarter of 2022 was $44.1 million, or $3.47 per basic and $3.41 per diluted share, compared to net loss of $0.4 million, or $0.03 per basic and diluted share, in the first quarter of 2021, as a result of the factors discussed above.

Adjusted non-GAAP net income* for the first quarter of 2022 was $52.2 million, or $4.10 per basic and $4.04 per diluted share, compared to adjusted non-GAAP net income* of $3.2 million, or $0.24 per basic and diluted share, in the first quarter of 2021.

2022 Full Year Expense Guidance

Adjusted non-GAAP R&D expense* is expected to be in the range of $46 million to $50 million, as compared to $32.5 million in 2021.
Adjusted non-GAAP SG&A expense* is expected to be in the range of $54 million to $58 million, as compared to $54.9 million in 2021.
The guidance excludes expense for operating Acacia in the event of successful acquisition.
Liquidity

As of March 31, 2022, Eagle had $69.5 million in cash and cash equivalents plus $130.9 million in net accounts receivable, and $24.0 million in outstanding debt. Therefore, as of March 31, 2022, Eagle had net cash plus receivables of $176.4 million.

In the first quarter of 2022, Eagle repurchased $8.1 million of its common stock as part of its current $160.0 million Share Repurchase Program. From August 2016 through March 31, 2022, Eagle has repurchased $236.1 million of its common stock.

Conference Call

As previously announced, Eagle management will host its first quarter 2022 conference call as follows:

Webcast (live and replay) www.eagleus.com, under the "Investor + News" section
A replay of the conference call will be available for one week after the call’s completion by dialing 888-562-2826 (US) or 402-220-7355 (International) and entering conference call ID EGRXQ122. The webcast will be archived for 30 days at the aforementioned URL.

On May 9, 2022 Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL), a clinical-stage biopharmaceutical company pursuing novel therapeutics for non-alcoholic steatohepatitis (NASH), reported acceptance of four abstracts for oral presentation at the European Association for the Study of the Liver’s (EASL) International Liver Congress, including a late-breaker presentation of data from the Phase 3 MAESTRO-NAFLD-1 trial, as well as other resmetirom clinical development program updates (Press release, Synta Pharmaceuticals, MAY 9, 2022, View Source [SID1234613875]). The Company also reported financial results for the first quarter of 2022, including the completion of a $250 million term loan facility to support resmetirom clinical and commercial development objectives and position Madrigal for a potential first-to-market launch in NASH. The company drew $50 million from the facility at closing and has the ability to draw a further $200 million under the agreement.

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Paul Friedman, M.D., Chief Executive Officer of Madrigal, stated, "The MAESTRO-NAFLD-1 data as described below have reinforced our confidence in the safety and potential efficacy of resmetirom in treating non-cirrhotic NASH with significant fibrosis. We look forward to sharing detailed MAESTRO-NAFLD-1 results in a late-breaking presentation at EASL followed by topline results from the MAESTRO-NASH biopsy study in Q4. Based on the totality of efficacy data generated thus far in our clinical development program, we believe resmetirom can both address the underlying drivers of NASH in the liver and also reduce the level of fibrosis that is associated with progression to more advanced disease."

Dr. Friedman added, "The term loan facility we are announcing today strengthens Madrigal’s balance sheet, providing an additional source of funding that can be drawn at the appropriate times to meet our operational needs and support our strategic priorities, including a new MAESTRO study and the ramp-up for the potential launch of resmetirom in the U.S."

Becky Taub, M.D., Chief Medical Officer and President of Research & Development of Madrigal, stated, "We are planning to expand our NASH development program by initiating a second study in the next few months to complement the clinical outcomes portion of MAESTRO-NASH; this second study, MAESTRO-NASH Outcomes, will non-invasively examine liver-related outcomes (decompensation events) in patients with early NASH cirrhosis. In contrast, MAESTRO-NASH relies primarily on serial liver biopsy to measure progression to cirrhosis. Resmetirom has been studied in over 180 patients with well-compensated NASH cirrhosis in an open label arm of MAESTRO-NAFLD-1. The safety and efficacy results that will be presented at EASL are supportive of a potential for benefit in this population. A positive outcome in this study, in a group of patients with the highest unmet need, has the potential to significantly broaden the label for resmetirom and increase the commercial opportunity. Furthermore, it is expected to accelerate the path to full approval and enhance the statistical power to assess benefit in patients with non-cirrhotic NASH. The addition of MAESTRO-NASH Outcomes does not alter our timeline for the subpart H NDA submission in non-cirrhotic NASH that is based on the results of the liver biopsy portion of MAESTRO-NASH."

Dr. Taub added, "As we have continued to gain confidence that we will achieve both the NASH resolution as well as the fibrosis improvement endpoints in the MAESTRO-NASH biopsy study we are moving one point fibrosis reduction up the hierarchy to a primary endpoint along with NASH resolution. While we expect to achieve both endpoints, dual primaries allow for a successful outcome of the study that can be filed for subpart H approval if either the NASH resolution or one point fibrosis reduction liver biopsy endpoint is met."

Stephen Harrison, M.D., Medical Director for Pinnacle Clinical Research, San Antonio, Texas, Visiting Professor of Hepatology, Oxford University, and Principal Investigator of the MAESTRO studies commented, "There is an urgent need for NASH treatments that can prevent progression to hepatic decompensation in patients at the early stages of NASH cirrhosis, but few late-stage development programs have focused on this population. The MAESTRO-NASH Outcomes study will help us determine if resmetirom can benefit patients with more advanced disease and achieve the endpoints that are valued most by healthcare providers, regulators, payers and, most importantly, patients."

Clinical Program Updates

Late-Breaking Presentation and Multiple Oral Presentations at EASL

Multiple resmetirom abstracts have been accepted at EASL’s International Liver Congress taking place June 22-26 in London:

Late-breaking presentation: "Primary data analyses of MAESTRO-NAFLD-1, a 52 week double-blind placebo-controlled phase 3 clinical trial of resmetirom in patients with NAFLD" [Saturday, June 25 at 3:00 PM. Presenter: Stephen Harrison]

Oral presentation: "Impact of resmetirom-mediated reductions in liver volume and steatosis compared with placebo on the quantification of fibrosis using second harmonic generation in a serial liver biopsy study" [Thursday, June 23 at 4:00 PM. Presenter: Dean Tai]

Oral presentation: "Utility of FIB-4 thresholds to identify patients with at-risk F2-F3 NASH based on screening data from a 2000 patient biopsy confirmed cohort of resmetirom Phase 3 clinical trial, MAESTRO-NASH" [Saturday, June 25 at 9:15 AM. Presenter: Jörn Schattenberg]

Oral presentation: "Biomarkers, imaging and safety in a well-compensated NASH cirrhotic cohort treated with resmetirom, a thyroid hormone receptor beta agonist, for 52 weeks" [Saturday, June 25 at 5:45 PM. Presenter: Stephen Harrison]

Poster: "A higher Fibrosis-4 (FIB-4) score is associated with higher healthcare costs and hospitalizations in patients with nonalcoholic steatohepatitis" [Presenter: Elliot Tapper]

Poster: "Retrospective AI-based measurement of NASH histology (AIM-NASH) analysis of biopsies from Phase 2 study of Resmetirom confirms significant treatment-induced changes in histologic features of non-alcoholic steatohepatitis" [Presenter: Janani Iyer]

Additional Phase 3 MAESTRO-NAFLD-1 Data

In January, Madrigal announced that primary and key secondary endpoints from the double-blind, placebo-controlled, 969-patient MAESTRO-NAFLD-1 safety study were achieved; resmetirom was safe and well-tolerated and provided significant reductions in liver fat, LDL-c and other atherogenic lipids vs. placebo.

Similar to what has been reported for the 100 mg open-label arm, patients in the resmetirom 80 mg and 100 mg double-blind arms achieved reductions in ALT (p=0.002; <0.0001) relative to placebo. ALT increases ≥3 times the upper limit of normal occurred in 0.61% in the resmetirom 80 mg group, 0.31% in the 100 mg group and 1.6% of patients in the placebo group.

Treatment-emergent adverse events ≥ grade 3 in severity occurred in 7.6% of patients in the resmetirom 80 mg group, 9.0% in the 100 mg group and 9.1% in the placebo group. Withdrawals due to adverse events were 2.4% in the 80 mg group, 2.8% in the 100 mg group and 1.3% in the placebo group. GI-related adverse events (diarrhea, nausea) were increased relative to placebo at the initiation of therapy but not after the first few weeks.

FibroScan CAP (controlled attenuation parameter) scores reflective of hepatic fat were statistically significantly (p<0.0001) reduced in resmetirom arms as compared with placebo. FibroScan liver stiffness reductions were similar in the 100 mg open-label and double-blind arms. Responder analyses of FibroScan vibration-controlled transient elastography (VCTE) reduction and % reduction from baseline comparing resmetirom 100 mg open-label and double-blind arms with placebo showed a significant increase in responders in resmetirom treatment arms (~44% averaged across the arms) compared with placebo (25%); magnetic resonance elastography (MRE) responders as measured by kPa reduction were significantly greater in resmetirom-treated groups compared with placebo. Mean reduction in FibroScan VCTE in resmetirom double-blind patients were greater than placebo but not statistically significant.

Detailed results of MAESTRO-NAFLD-1 are under embargo until the late-breaking presentation at EASL.

MAESTRO-NASH Outcomes Study

In the next few months, Madrigal plans to initiate a second NASH outcomes study, MAESTRO-NASH Outcomes, a randomized double-blind placebo-controlled study in approximately 700 patients with early NASH cirrhosis to allow for non-invasive monitoring of progression to liver decompensation events. Several biomarker and imaging techniques will also be employed to assess correlates with disease progression. Ongoing open-label studies of more than 180 patients with well-compensated NASH cirrhosis (MAESTRO-NAFLD-1 open-label arm) support the potential of resmetirom in this patient population.

Previously reported data from the patients with NASH cirrhosis in the open-label arm of MAESTRO-NAFLD-1 demonstrated that resmetirom reduced hepatic fat, liver volume, liver enzymes, fibrosis markers and atherogenic lipids. Madrigal will be presenting additional results from the MAESTRO-NAFLD-1 cirrhosis population in an oral presentation at EASL.

Term Loan Facility to Support Expansion of Clinical Development Program and Resmetirom Launch

Madrigal has secured a $250 million term loan facility with Hercules Capital, Inc. (NYSE: HTGC), a leader in customized specialty financing for life sciences companies. The committed capital strengthens Madrigal’s balance sheet, providing an additional source of funding both to support the expanded clinical program and ramp-up for a potential launch of resmetirom in the U.S.

Under the terms of the loan agreement, $50 million was drawn at closing. Madrigal may also draw an additional $125 million in two separate tranches upon achievement of resmetirom clinical and regulatory milestones. An additional $75 million may be drawn by Madrigal, subject to the approval of Hercules Capital. The loan facility has a floor rate of 7.45% and adjusts with future changes in the prime rate, subject to the floor rate. The loan bears initial interest at a rate of 7.95%. Madrigal will pay interest-only for a period of 30 months, which may be extended to 60 months upon the achievement of certain milestones. The loan matures in May 2026 and may be extended an additional year upon the achievement of certain milestones.

R. Bryan Jadot, Senior Managing Director and Life Sciences Group Head at Hercules Capital stated, "Hercules is pleased to provide both upfront funding and future potential funding capacity to help Madrigal deliver on its important mission to address a large unmet medical need and improve the lives of people suffering from NASH and liver disease."

Additional details of the loan agreement will be filed with the Securities and Exchange Commission on a Current Report on Form 8-K.

Financial Results for the Three Months Ended March 31, 2022

As of March 31, 2022, Madrigal had cash, cash equivalents and marketable securities of $220.0 million, compared to $270.3 million at December 31, 2021. The decrease in cash and marketable securities resulted primarily from cash used in operations of $49.9 million.

Operating expenses were $57.6 million for the three month period ended March 31, 2022, compared to $53.0 million in the comparable prior year period.

Research and development expenses for the three month period ended March 31, 2022 were $47.9 million, compared to $45.8 million in the comparable prior year period. 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 month period ended March 31, 2022 were $9.7 million, compared to $7.2 million in the comparable prior year period. The increase in general and administrative expenses for the latest three month period is due primarily to increases in commercial preparation activities, including an increase in headcount.

Interest income for the three month period ended March 31, 2022 was $0.1 million, compared to $0.2 million in the comparable prior year period. The decrease in interest income was due primarily to a lower average principal balance in our investment account in 2022.

Conference Call at 8:00 am EST

Madrigal will hold a conference call and webcast at 8:00 am EST. To access the conference call, please dial (833) 660-2754 for domestic callers or (409) 350-3497 for international callers and reference conference ID: 9765409. To access the live webcast of the call with slides please visit the Investors section of Madrigal’s website or click here. An archived webcast will be available on the Madrigal website after the event.

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

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 two primary surrogate endpoints on biopsy will be NASH resolution, with at least a 2-point reduction in NAS (NASH Activity Score), and with no worsening of fibrosis OR a one point decrease in fibrosis with no worsening of NASH. A key secondary endpoint is lowering of LDL-cholesterol. The planned target enrollment was announced as completed on June 30, 2021.

The first 900 patients in the MAESTRO-NASH study will continue on therapy after the initial 52-week treatment period; up to another 1,100 patients are to be added using the same randomization plan. 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 was initiated in December 2019 and the 52-week Phase 3 multi-center, double-blind, randomized, placebo-controlled study of resmetirom in over 1,200 patients with non-alcoholic fatty liver disease (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 is to evaluate the safety and tolerability of resmetirom. An open-label extension study, MAESTRO-NAFLD-OLE is ongoing.

Patients in the 52-week blinded phase of MAESTRO-NAFLD-1 were randomized 1:1:1:1 to receive resmetirom 80 mg once a day, 100 mg once a day, placebo or a 100 mg resmetirom open label arm. MAESTRO-NAFLD-1 (unlike MAESTRO-NASH), did not include a liver biopsy and represents a "real-life" NASH study. NASH or presumed NASH was documented using historical liver biopsy or non-invasive techniques including FibroScan and magnetic resonance imaging, proton density fat fraction (MRI-PDFF) respectively. Using non-invasive 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. These key secondary endpoints included LDL-cholesterol, apolipoprotein B and triglyceride (TG) lowering; and reduction of liver fat as determined by MRI-PDFF. Additional secondary and exploratory endpoints were 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.