Madrigal Pharmaceuticals Reports 2018 Second Quarter Financial Results and Reviews Key Clinical Achievements

On August 7, 2018 Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL) reported its second quarter 2018 financial results and described recent clinical and corporate accomplishments including (Press release, Synta Pharmaceuticals, AUG 7, 2018, View Source [SID1234528529]):

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· Positive Phase 2 Clinical Results – MGL-3196 demonstrated highly statistically significant results for the key 36-week endpoints in its Phase 2 clinical trial in non-alcoholic steatohepatitis (NASH), including statistically significant reductions of liver fat and resolution of NASH

· Madrigal’s abstract "In a Placebo-Controlled 36-Week Phase 2 Trial, Treatment with MGL-3196 Compared to Placebo Results in Significant Reductions in Hepatic Fat (MRI-PDFF), Liver Enzymes, Fibrosis Biomarkers, Atherogenic Lipids, and Improvement in NASH on Serial Liver Biopsy" has been selected for oral presentation at The Liver Meeting 2018 in San Francisco. The presentation will take place on Monday, November 12, 2018, at 8:15 AM during the Presidential Plenary — Clinical Science

· Increased Capital Position — Madrigal completed an underwritten registered public offering in which the gross proceeds to Madrigal from the offering, before deducting the underwriting discounts and commissions and other estimated offering expenses, were approximately $329 million

· Progress in out-licensed legacy oncology programs — Madrigal’s licensee for its Hsp90 inhibitor program, Aldeyra Therapeutics, Inc., recently announced that, ADX-1612, its lead Hsp90 compound, is being advanced in multiple indications: mesothelioma, ovarian cancer and lymphoproliferative immune disease

"We believe the 36-week data from our recently completed Phase 2 clinical study of MGL-3196 in patients with NASH suggest a high likelihood of success in a similarly designed Phase 3 study, for which we are actively preparing, pending regulatory agreement," stated Paul Friedman, M.D., Chief Executive Officer of Madrigal. "With our financial raise completed, which provided more than $300 million of additional capital, we are in a strong position to expedite the MGL-3196 development program in NASH and dyslipidemias."

Becky Taub, M.D., CMO and Executive VP, Research & Development of Madrigal added, "We believe the totality of data from our clinical and preclinical studies to date, including the consistency of the various parameters related to clinical benefits and safety, demonstrate the potential of MGL-3196 to resolve NASH and improve multiple atherogenic lipids. We are pleased our abstract was selected by AASLD as an oral presentation in the presidential plenary clinical session and look forward to presenting these encouraging clinical outcomes in November at The Liver Meeting 2018."

Financial Results for the Three Months and Six Months Ended June 30, 2018

As of June 30, 2018, Madrigal had cash, cash equivalents and marketable securities of $490.3 million, compared to $191.5 million at December 31, 2017. The increase in cash and marketable securities resulted primarily from the net proceeds of $311.8 million from Madrigal’s public offering of common stock in June 2018, partially offset by cash used in operations of $14.0 million.

Operating expenses were $7.8 million and $14.9 million, respectively, for the three month and six month periods ended June 30, 2018, compared to $8.4 million and $14.5 million in the comparable prior year periods.

Research and development expenses for the three month and six month periods ended June 30, 2018 were $5.1 million and $10.3 million, respectively, as compared to $6.8 million and $11.2 million in the comparable prior year periods. The decreases are primarily attributable to completion of treatment in our Phase 2 clinical studies in 2018.

General and administrative expenses for the three month and six month periods ended June 30, 2018 were $2.7 million and $4.6 million, respectively, as compared to $1.6 million and $3.3 million in the comparable prior year periods. The increases are due primarily to higher non-cash stock compensation expense from stock option awards.

Interest income for the three month and six month periods ended June 30, 2018 was $1.2 million and $1.9 million, respectively, as compared to $92 thousand and $168 thousand in the comparable prior year periods. The change in interest income was due primarily to a higher average principal balance in our investment account in 2018.

Out-Licensed Legacy Oncology Programs

Madrigal’s licensee for its Hsp90 inhibitor program, Aldeyra Therapeutics, Inc., provided a pipeline update during its June 2018 Research Day. ADX-1612 is a novel Hsp90 inhibitor in development for the treatment of post-transplant lymphoproliferative disorder and cancer. Hsp90 is a protein that facilitates cell replication, which is excessive and uncontrolled in certain inflammatory diseases and cancer. ADX-1612 is currently being studied in investigator-sponsored trials for mesothelioma, with clinical results expected in the second half of 2018, and ovarian cancer, with Phase 2 clinical trial initiation expected in the second half of 2018. Aldeyra is further developing ADX-1612 for the

treatment of lymphoproliferative immune disease, with Phase 2 clinical testing expected to start in 2019.

Clinical Program Summaries for MGL-3196

NASH

Non-alcoholic Steatohepatitis (NASH) is a common liver disease in the United States and worldwide, unrelated to alcohol use, that is characterized by a build-up of fat in the liver, inflammation, damage (ballooning) of hepatocytes and increasing fibrosis. Although people with NASH may feel well and often do not know they have the disease, NASH can lead to permanent damage, including cirrhosis and impaired liver function in a high percentage of patients.

In October 2016, the first patient was treated in the ongoing Phase 2 trial of MGL-3196 for the treatment of NASH. The randomized, double-blind, placebo-controlled, multi-center Phase 2 study enrolled 125 patients 18 years of age and older with liver biopsy-confirmed NASH and included approximately 25 clinical sites in the United States. Patients were randomized to receive either MGL-3196 or placebo in a 2:1 ratio.

The primary endpoint of the study was the reduction of liver fat at 12 weeks compared with baseline (relative change), assessed by MRI-PDFF. Key secondary endpoints at 36 weeks included: reduction in liver fat compared with baseline (relative change), also assessed by MRI-PDFF; a two-point reduction in NAS (NALFD activity score) on biopsy; resolution of NASH on biopsy; and, safety and tolerability based on adverse events and changes in laboratory values.

The primary endpoint of the study at 12 weeks was achieved. Liver fat was reduced by 36.3% in all MGL-3196 treated patients (78) and 42.0% in a pre-specified group of high exposure MGL-3196 treated patients (44/78), as compared with 9.6% median reduction in liver fat in 38 placebo treated patients. These results were statistically significant (p<0.0001) for both MGL-3196 treatment groups. Further, 75% of the high-exposure MGL-3196 treated patients showed liver fat reductions of >30%.

At 36 weeks, MGL-3196 achieved multiple key secondary endpoints including a sustained highly significant (p<0.001) reduction in liver fat compared to placebo as measured by MRI-PDFF; mean relative fat reduction for MGL-3196 was 37% versus 8.9% for placebo. MGL-3196 was associated with a greater percentage of subjects with a 2-point improvement in NAS (56% of 73 patients vs 32% of 34 placebo subjects, p=0.02). NASH resolution (NR) was seen in 27% of MGL-3196 compared with 6% of placebo subjects, p=0.02. MGL-3196 patients with > 30% fat reduction on Week 12 MRI-PDFF demonstrated a higher percentage of 2-point improvement in NAS (70%, p=0.001) and NR (39%, p=0.001) compared with placebo, demonstrating a strong relationship between early reduction in liver fat as demonstrated by week 12 MRI-PDFF and NASH improvement on liver biopsy at Week 36. In patients with NASH Resolution,

35% of the MGL-3196 treated patients and no placebo patients had more advanced NASH (baseline NAS >5).

At Week 36, MGL-3196 treated patients showed sustained reduction of fibrosis biomarkers. In MGL-3196 patients with NASH resolution, fibrosis also resolved in 50% of patients and was decreased statistically significantly reduced relative to all placebo patients.

There were statistically significant reductions in liver enzymes in MGL-3196 treated patients compared to placebo treated patients; reductions of greater magnitude were achieved with longer duration of MGL-3196 treatment. Statistically significantly more MGL-3196 treated patients than placebo treated patients had normalization of ALT (alanine transaminase).

Similar to week 12, at week 36 there were sustained, statistically significant reductions in low-density lipoprotein cholesterol (LDL-C), triglycerides, ApoB and lipoprotein(a).

MGL-3196 was well tolerated in this trial with mostly mild and a few moderate AEs which were balanced between drug treated and placebo patients. An increase in incidence of mild transient diarrhea in MGL-3196-treated, often a single episode, at the start of treatment. Diarrhea incidence was not increased later in the study.

Based on liver enzyme inclusion criteria, some patients are receiving extended treatment beyond 36 weeks for up to 36 additional weeks. All patients in this extension study will receive MGL-3196 and only non-invasive assessments will be made, including serial MRI-PDFF, safety labs, and circulating biomarkers.

Additional information about the study [NCT02912260] can be obtained at www.ClinicalTrials.gov.

Heterozygous familial hypercholesterolemia (HeFH), and a much rarer form called homozygous familial hypercholesterolemia (HoFH), are severe genetic dyslipidemias typically caused by inactivating mutations in the LDL receptor. Both forms of FH lead to early onset cardiovascular disease. HeFH, the most common dominantly inherited disease, is present in up to 1 in 200 people; the disease is found in higher frequencies in certain more genetically homogenous populations. Treatments exist for both HeFH and HoFH but many patients (as many as 40 percent of HeFH patients) are not able to reach their cholesterol (LDL-C) reduction goals on these therapies, reflecting the lifetime burden of cholesterol buildup in their bodies. Based on evidence of impressive LDL cholesterol lowering in Phase 1, and data suggesting that MGL-3196 has a mechanism of action that is different from and complementary to statins, Madrigal initiated a Phase 2 proof-of-concept trial in HeFH in February 2017 and enrolled 116 patients.

In this Phase 2 HeFH trial, patients who were not at their LDL-C goal were randomized in a 2:1 ratio to receive either MGL-3196 or placebo, in addition to their current cholesterol lowering regimen, which included approximately 75% taking high intensity statins (20/40 mg rosuvastatin or 80 mg atorvastatin), and about 2/3 of patients also taking ezetimibe. MGL-3196 treated patients (placebo corrected) achieved highly significant (p< 0.0001) LDL-C lowering of 18.8%, and 21% LDL-C lowering in those on an optimal dose of MGL-3196. LDL-C lowering was 28.5% in MGL-3196 treated compared to placebo in a prespecified group of patients who did not tolerate high intensity statin doses. Highly significant reductions (p<0.0001) relative to placebo were also observed with ApoB, triglycerides (TG) (25-31%), apolipoprotein CIII (Apo CIII) and Lp(a) (25-40%) in all MGL-3196 treated patients and prespecified subgroups, irrespective of statin treatment.

MGL-3196 was well-tolerated with primarily mild and some moderate AEs, the numbers of which were balanced between placebo and drug-treatment groups.

About MGL-3196

Among its many functions in the human body, thyroid hormone, through activation of its beta receptor, plays a central role in controlling lipid metabolism, impacting a range of health parameters from levels of serum cholesterol and triglycerides to the pathological buildup of fat in the liver. Attempts to exploit this pathway for therapeutic purposes in cardio-metabolic and liver diseases have been hampered by the lack of selectivity of older compounds for the thyroid hormone receptor (THR)-β, chemically-related toxicities and undesirable distribution in the body.

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. Madrigal believes that MGL-3196 is the first orally administered, small-molecule, liver- directed, truly β-selective THR agonist. MGL- 3196 has now demonstrated in two Phase 2 double-blind, placebo-controlled trials in NASH and HeFH the potential for a broad array of therapeutically beneficial effects, improving components of both metabolic syndrome, such as insulin resistance and dyslipidemia, and fatty liver disease, including lipotoxicity and inflammation. Based on evidence of these pleiotropic actions, coupled with an excellent safety profile, Madrigal plans to initiate a Phase 3 clinical program in NASH and dyslipidemias.

Sierra Oncology to Present at the Wedbush PacGrow Healthcare Conference in New York

On August 7, 2018 Sierra Oncology, Inc. (Nasdaq: SRRA), a clinical stage drug development company focused on advancing next generation DNA Damage Response (DDR) therapeutics for the treatment of patients with cancer, reported that Dr. Nick Glover, President and Chief Executive Officer, will present an overview of the company at the 2018 Wedbush PacGrow Healthcare Conference being held in New York on August 14-15 (Press release, Sierra Oncology, AUG 7, 2018, View Source [SID1234528571]). The presentation is scheduled for 9:10 a.m. ET on Wednesday, August 15. A live audio webcast and archive of the presentation will be accessible through the Sierra Oncology website at www.sierraoncology.com.

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eidos therapeutics reports second quarter 2018 financial results and provides corporate update

On August 7, 2018 Eidos Therapeutics, Inc. (Eidos) (Nasdaq:EIDX), a clinical stage biopharmaceutical company focused on addressing the large and growing unmet need in diseases caused by transthyretin (TTR) amyloidosis (ATTR), reported its financial results for the quarter ended June 30, 2018 and provided an update on the Company’s recent achievements (Press release, Eidos Therapeutics, AUG 7, 2018, View Source [SID1234576275]).

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"With the proceeds from our IPO and Series B financing, we are well positioned to continue the momentum of developing AG10 as a disease-modifying therapy for ATTR," said Neil Kumar, PhD, chief executive officer of Eidos. "Specifically, we plan to complete our ongoing Phase 2 trial in ATTR-CM patients by the end of 2018 and initiate Phase 3 studies in ATTR-CM and ATTR-PN patients in 2019."

Recent Achievements and Upcoming Milestones

Initiated and completed enrollment in the ongoing Phase 2 trial in ATTR-CM patients.
Completed Series B preferred stock financing raising $64 million.
Completed initial public offering, with total gross proceeds of $122.2 million including exercise of underwriters’ option to purchase additional shares, from the sale of 7.2 million shares of common stock.
Complete data from Phase 1 study of AG10 in healthy volunteers to be presented at poster presentation at Heart Failure Society of America 22nd Annual Scientific Meeting (September 15-18).
Top-line results from ongoing Phase 2 study of AG10 in symptomatic ATTR-CM patients to be announced by the end of 2018.
Financial Results for the Second Quarter 2018

Cash and cash equivalents totaled $176.7 million at June 30, 2018 compared with $5.5 million at December 31, 2017, reflecting the $112.2 million of net proceeds from our initial public offering in June 2018 and $64.0 million related to the Series B preferred stock financing.

Research and development expenses were $7.4 million for the second quarter of 2018, compared to $1.3 million for the same period of 2017, an increase of $6.1 million. The increase was primarily due to increased expenses for contract consultants, contract manufacturing and other activities for AG10 clinical trials and increases in headcount and related salaries and expenses.

General and administrative expenses were $1.9 million for the second quarter of 2018 compared to $0.5 million for the same period in 2017, an increase of $1.4 million. The increase was primarily due to increased salaries and employee-related expenses and increases in professional fees and services in connection with becoming a public company.

Net loss for the quarter ended June 30, 2018 was $10.6 million or $1.38 per common share, compared to a net loss of $1.7 million or $0.49 per common share for the same period in 2017.

About AG10

AG10 is an orally-administered small molecule designed to potently stabilize tetrameric transthyretin, or TTR, thereby halting at its outset the series of molecular events that give rise to amyloidosis, or ATTR. AG10 is currently being examined in a Phase 2 clinical trial in patients with ATTR cardiomyopathy. Top-line results from this trial are expected to be reported by the end of 2018.

AG10 was designed to mimic a naturally-occurring variant of the TTR gene (T119M) that is considered a "rescue mutation" because it has been shown to prevent ATTR in individuals carrying pathogenic, or disease-causing, mutations in the TTR gene. To our knowledge, AG10 is the only TTR stabilizer in development that has been observed to mimic the "super-stabilizing" properties of this rescue mutation.

XOMA Reports Second Quarter 2018 Financial Results

On August 7, 2018 XOMA Corporation (Nasdaq: XOMA), a pioneer in the discovery, development and licensing of therapeutic antibodies, reported its second quarter 2018 financial results (Press release, Xoma, AUG 7, 2018, View Source [SID1234528769]).

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"We continue to focus our efforts on expanding our portfolio of partner-funded programs through both acquisition and out-license activities," said Jim Neal, Chief Executive Officer at XOMA. "We believe we are well-positioned to execute on our royalty-aggregator strategy to create near- and long-term value for shareholders."

Financial Results
XOMA recorded total revenues of $2.3 million for the second quarter of 2018, $1.8 million of which was recognized under XOMA’s license agreement and common stock purchase agreement with Rezolute. In the second quarter of 2017, XOMA reported $10.9 million in revenue, $10.0 million of which was milestone revenue earned under one of the Company’s license agreements with Novartis.

Research and development (R&D) expenses were $0.4 million for the second quarter of 2018, compared to $2.9 million for the second quarter of 2017. The decrease in R&D expenses was due primarily to reductions of $1.0 million in clinical trial costs, $0.4 million in consulting costs, $0.4 million in the allocation of facilities costs, $0.4 million in external manufacturing activities, and $0.1 million in stock-based compensation. The significant reduction in R&D spending is a result of the discontinuation of clinical trial activities and the execution of the Company’s royalty-aggregator business model.

General and administrative (G&A) expenses were $4.4 million for the second quarter of 2018, compared to $5.2 million for the second quarter of 2017. The decrease in G&A expenses was due primarily to reductions of $0.9 million in stock-based compensation, $0.2 million in legal and accounting fees, and $0.1 million in information technology costs, partially offset by increases of $0.2 million in consulting services and $0.4 million in the allocation of facilities costs due to a greater proportion of G&A personnel after the Company’s restructuring activities.

The Company recorded a lease-related restructuring charge of $0.5 million in the second quarter of 2018, compared with $1.5 million for personnel-related restructuring expenses in the same period of 2017.

Total other income, net was $1.2 million for the second quarter of 2018, compared to other expense of $0.7 million for the second quarter of 2017. During the second quarter of 2018, we recorded $1.0 million in income from Ology Bioservices related to the disposition of our biodefense business in March 2016. Separately, we received long-term equity securities that consisted of an investment in Rezolute Inc.’s common stock under the terms of a licensing agreement. As of June 30, 2018, the fair value of the long-term equity securities had decreased, and we recognized a loss of $0.4 million.

Net loss for the second quarter of 2018 was $1.9 million, compared to net income of $0.3 million for the second quarter of 2017.

On June 30, 2018, XOMA had cash and cash equivalents of $38.7 million. The Company ended December 31, 2017, with cash and cash equivalents of $43.5 million. The Company’s current cash and cash equivalents are expected to be sufficient to fund its operations for multiple years.

ADC Therapeutics Doses First Patient in Pivotal Clinical Trial of ADCT-402 in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma

On August 7, 2018 ADC Therapeutics, an oncology drug discovery and development company that specializes in the development of proprietary antibody drug conjugates (ADCs), reported that the first patient has been dosed in its Phase II clinical trial intended to support the submission of Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) (Press release, ADC Therapeutics, AUG 7, 2018, View Source [SID1234596075]). The clinical trial is evaluating the efficacy and safety of ADCT-402 (loncastuximab tesirine) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

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At the 2017 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, the Company presented interim Phase I data on ADCT-402 in 138 evaluable, heavily pre-treated lymphoma patients who had failed, or were intolerant to, any established therapy known to provide clinical benefit, with a median of three prior therapies. At the time, for the 49 response-evaluable patients in Part 1 of the study (dose escalation) with DLBCL who received ADCT-402 at doses greater than or equal to 120 μg/kg, the overall response rate (ORR) was 55 percent (27/49), with 18 patients achieving a complete response (37 percent) and 9 patients achieving a partial response (18 percent).

The primary endpoint of the Phase II, multi-center, open-label, single-arm trial is the ORR in patients treated with ADCT-402, as confirmed by central review. Secondary endpoints include assessments of duration of response, complete response rate, relapse-free survival, progression-free survival and overall survival, as well as safety, pharmacokinetics and health-related quality of life. The trial will enroll approximately 140 patients with relapsed or refractory DLBCL at multiple centers in the USA and Europe.

"We are pleased to have dosed the first patient in our registrational Phase II clinical trial evaluating ADCT-402 in patients with DLBCL who have relapsed and have refractory disease after two or more multi-agent treatment regimens. Our Phase I clinical trial of ADCT-402 in non-Hodgkin lymphoma showed significant activity in patients with DLBCL and an acceptable safety profile," said Jay Feingold, MD, PhD, Chief Medical Officer and Senior Vice President of Clinical Development at ADC Therapeutics. "Unfortunately, there is no effective treatment for patients with multiple relapsed and refractory DLBCL, so we are excited about the potential to improve outcomes in these patients with ADCT-402 in a single-arm trial. We anticipate reporting results from the Phase II trial in the third quarter of 2019 and are hopeful that the data will support our submission of a BLA to the FDA."

Alex Spira, MD, PhD, FACP, Director of Virginia Cancer Specialists Research Institute and Clinical Assistant Professor of Oncology at Johns Hopkins School of Medicine, added, "Patients with DLBCL who have relapsed or are refractory after second-line chemotherapy face a very poor prognosis. There is a

significant unmet need for an effective new treatment option for this patient population, and we believe ADCT-402 has the potential to help impact patient outcomes in this disease."

For more information about the Phase II clinical trial, please visit www.clinicaltrials.gov (identifier NCT03589469).

ADC Therapeutics also plans to initiate multiple combination studies with ADCT-402 in the fourth quarter of 2018.

About Diffuse Large B-Cell Lymphoma (DLBCL)

Non-Hodgkin lymphoma (NHL) is the seventh most common type of cancer in the U.S., and accounted for an estimated 4.3 percent of new cancer cases in 2017.1 Diffuse large B-cell lymphoma (DLBCL) accounts for nearly one-third (32.5 percent) of NHL.2 The most common initial treatment for patients with DLBCL is chemo-immunotherapy. Response to initial treatment is high, but more than half of patients do not have long-term disease control.3 The current standard of care for relapsed DLBCL is additional chemotherapy, which can be followed by stem cell transplantation (SCT). The prognosis for relapsed patients is poor, especially for those with chemotherapy-refractory disease with a short interval between remission and relapse or those who relapse after high-dose therapy and SCT. There is a significant unmet need for an effective treatment for patients with relapsed or refractory DLBCL.

About ADCT-402

ADCT-402 is an antibody drug conjugate (ADC) composed of a humanized monoclonal antibody that binds to human CD19, conjugated through a linker to a pyrrolobenzodiazepine (PBD) dimer toxin. Once bound to a CD19-expressing cell, ADCT-402 is internalized into the cell where enzymes release the PBD-based warhead. CD19 is a clinically validated target for the treatment of B-cell malignancies. The PBD-based warhead has the ability to form highly cytotoxic DNA interstrand cross-links, blocking cell division and resulting in cell death. Preliminary data from a Phase I clinical trial in relapsed or refractory B-cell non-Hodgkin lymphoma demonstrate ADCT-402 has significant activity in patients with diffuse large B-cell lymphoma (DLBCL). ADCT-402 is also being evaluated in an ongoing Phase I clinical trial in patients with relapsed or refractory B-cell lineage acute lymphoblastic leukemia (B-ALL). The U.S. Food and Drug Administration has granted orphan drug designation to ADCT-402 for the treatment of DLBCL and mantle cell lymphoma.