On May 7, 2020 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported that new data from clinical trials of 19 approved and investigational medicines across 21 cancer types will be presented at the ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program organized by the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), which will be held May 29-31, 2020 (Press release, Genentech, MAY 7, 2020, View Source [SID1234557349]). A total of 120 abstracts that include a Roche medicine will be presented at this year’s meeting.

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"At ASCO (Free ASCO Whitepaper), we will present new data from many investigational and approved medicines across our broad oncology portfolio," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. "These efforts exemplify our long-standing commitment to improving outcomes for people with cancer, even during these unprecedented times. By integrating our medicines and diagnostics together with advanced insights and novel platforms, Genentech is uniquely positioned to deliver the healthcare solutions of the future."

Together with its partners, Genentech is pioneering a comprehensive approach to cancer care, combining new diagnostics and treatments with innovative, integrated data and access solutions for approved medicines that will both personalize and transform the outcomes of people affected by this deadly disease.

Key presentations

First results of tiragolumab, Genentech’s novel cancer immunotherapy designed to bind to TIGIT, will be shared. These results, from the Phase II CITYSCAPE study, examine tiragolumab in combination with Tecentriq (atezolizumab) compared with Tecentriq alone as an initial treatment for people with PD-L1-positive, locally advanced unresectable or metastatic non-small cell lung cancer (NSCLC). In addition, updated five-year overall survival rates with Alecensa (alectinib) in people living with treatment-naive anaplastic lymphoma kinase (ALK)-positive metastatic/advanced NSCLC will be presented. With five approved lung cancer medicines and an extensive pipeline across multiple subtypes, Genentech’s ultimate aim is to provide an effective treatment option for each person diagnosed with the disease, tailored to the unique characteristics of their tumors.

Studies featured from partnerships with Flatiron Health and Foundation Medicine demonstrate how the use of next-generation sequencing (NGS) may help inform treatment decisions, optimize testing and enable personalized therapy, including an ongoing additional study designed to prospectively link longitudinal, real-world clinical data with genomic, imaging and outcomes data for people with advanced lung cancers. The study is monitoring circulating tumor DNA (ctDNA) using FoundationOne Liquid, and tumor tissue samples will be genomically profiled using FoundationOne CDx.

Follow Genentech on Twitter via @Genentech and keep up to date with ASCO (Free ASCO Whitepaper) news and updates by using the hashtag #ASCO20.

Overview of key presentations featuring Genentech medicines at ASCO (Free ASCO Whitepaper) 2020

Medicine

Abstract title

Abstract number

Lung cancer

Tiragolumab

Primary analysis of a randomized, double-blind, phase II study of the anti-TIGIT antibody tiragolumab (tira) plus atezolizumab (atezo) versus placebo plus atezo as first-line (1L) treatment in patients with PD-L1-selected NSCLC (CITYSCAPE)

Abstract 9503 (oral)

Alecensa

Updated overall survival (OS) and safety data from the randomized, phase III ALEX study of alectinib (ALC) versus crizotinib (CRZ) in untreated advanced ALK+ NSCLC

Abstract 9518

(poster discussion 284)

Tecentriq

Patient-reported outcomes (PROs) in the randomized, phase III IMpower110 study of atezolizumab (atezo) vs chemotherapy in 1L metastatic NSCLC

Abstract 9594

(poster 360)

Tecentriq

IMpower150: exploratory analysis of brain metastases development

Abstract 9587

(poster 353)

Tecentriq

IMpower150: exploratory efficacy analysis in patients (pts) with bulky disease

N/A

e-publication

Flatiron Health data in lung cancer

Real World Data

A multi-stakeholder platform to prospectively link longitudinal real-world clinico-genomic, imaging, and outcomes data for patients with metastatic lung cancer

Abstract TPS2087

(poster 79)

Real World Data

Genomic testing among patients (pts) with newly diagnosed advanced non-small cell lung cancer (aNSCLC) in the United States: a contemporary clinical practice patterns study

Abstract 9592

(poster 358)

Solid tumors

Rozlytrek

Updated entrectinib data in children and adolescents with recurrent or refractory solid tumors, including primary CNS tumors

Abstract 107

(clinical science symposium)

Rozlytrek

Efficacy and safety of entrectinib in patients (pts) with NTRK-Fusion-Positive (NTRK-fp) solid tumors: an updated integrated analysis

Abstract 3605

(poster 335)

Genitourinary and gastrointestinal cancers

Tecentriq

IMvigor010: primary analysis from a phase III randomized study of adjuvant atezolizumab (atezo) versus observation (obs) in high-risk muscle-invasive urothelial carcinoma (MIUC)

Abstract 5000

(oral)

Tecentriq

Tumor, immune, and stromal characteristics associated with clinical outcomes with atezolizumab (atezo) + platinum-based chemotherapy (PBC) or atezo monotherapy (mono) versus PBC in metastatic urothelial cancer (mUC) from the phase III IMvigor130 study

Abstract 5011

(clinical science symposium)

Tecentriq

Phase Ib/II open-label, randomized evaluation of 2L atezolizumab (atezo) + PEGPH20 versus control in MORPHEUS-pancreatic ductal adenocarcinoma (M-PDAC) and MORPHEUS-gastric cancer (M-GC)

Abstract 4540

(poster 148)

Tecentriq, Avastin

Complete responses (CR) in patients receiving atezolizumab (atezo) + bevacizumab (bev) vs sorafenib (sor) in IMbrave150: a phase III clinical trial for unresectable hepatocellular carcinoma (HCC)

Abstract 4596

(poster 204)

Ipatasertib

Circulating tumor DNA (ctDNA) dynamics associate with treatment response and radiological progression-free survival (rPFS): analyses from a randomized phase II trial in metastatic castration-resistant prostate cancer (mCRPC)

Abstract 5508

(oral)

Blood cancer

Venclexta

Impact of premature venetoclax (Ven) discontinuation/interruption on outcomes in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL): Phase III MURANO study results

Abstract 8028

(poster 361)

Venclexta, Gazyva

Fixed-duration venetoclax-obinutuzumab for previously untreated patients with chronic lymphocytic leukemia: follow-up of efficacy and safety results from the multicenter, open-label, randomized, phase III CLL14 trial

Abstract 8027

(poster 360)

Gazyva

Comparison of efficacy and safety with obinutuzumab plus chemotherapy versus rituximab plus chemotherapy in patients with previously untreated follicular lymphoma: Updated results from the phase III Gallium Study

Abstract 8023

(poster 356)

Breast cancer

Kadcyla, Perjeta

Primary analysis of KAITLIN: A phase III study of trastuzumab emtansine (T-DM1) + pertuzumab versus trastuzumab + pertuzumab + taxane, after anthracyclines as adjuvant therapy for high-risk HER2-positive early breast cancer (EBC)

Abstract 500

(oral)

Kadcyla

Biomarker data from KATHERINE: A phase III study of adjuvant trastuzumab emtansine (T-DM1) vs trastuzumab (H) in patients with residual invasive disease after neoadjuvant therapy for HER2-positive breast cancer

Abstract 502

(oral)

About Tecentriq (atezolizumab)

Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1. Tecentriq is designed to bind to PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the re-activation of T cells. Tecentriq may also affect normal cells.

Tecentriq U.S. Indications

Tecentriq is a prescription medicine used to treat adults with:

A type of bladder and urinary tract cancer called urothelial carcinoma. Tecentriq may be used when your bladder cancer:

has spread or cannot be removed by surgery, and if you have any one of the following conditions:
you are not able to take chemotherapy that contains a medicine called cisplatin, and your cancer tests positive for "PD-L1", or
you are not able to take chemotherapy that contains any platinum regardless of "PD-L1" status, or
you have tried chemotherapy that contains platinum, and it did not work or is no longer working.
The approval of Tecentriq in these patients is based on a study that measured response rate and duration of response. Continued approval for this use may depend on the results of an ongoing study to confirm benefit.

A type of lung cancer called non-small cell lung cancer (NSCLC).

Tecentriq may be used with chemotherapy and other anti-cancer medicines as your first treatment when your lung cancer:
has spread or grown, and
is a type called "non-squamous NSCLC", and
your tumor does not have an abnormal "EGFR" or "ALK" gene.
Tecentriq may be used alone when your lung cancer:
has spread or grown, and
you have tried chemotherapy that contains platinum, and it did not work or is no longer working.
If your tumor has an abnormal "EGFR" or "ALK" gene, you should have also tried an FDA-approved therapy for tumors with these abnormal genes, and it did not work or is no longer working.
A type of breast cancer called triple-negative breast cancer (TNBC).

Tecentriq may be used with the medicine paclitaxel protein-bound when your breast cancer:
has spread or cannot be removed by surgery, and
your cancer tests positive for "PD-L1."
The approval of Tecentriq in these patients is based on a study that measured the amount of time until patients’ disease worsened. Continued approval for this use may depend on results of an ongoing study to confirm benefit.

A type of lung cancer called small cell lung cancer (SCLC).

Tecentriq may be used with the chemotherapy medicines carboplatin and etoposide as your first treatment when your lung cancer:
is a type called "extensive-stage small cell lung cancer," which means that it has spread or grown.
It is not known if Tecentriq is safe and effective in children.

Important Safety Information

What is the most important information about Tecentriq?

Tecentriq can cause the immune system to attack normal organs and tissues and can affect the way they work. These problems can sometimes become serious or life threatening and can lead to death.

Patients should call or see their healthcare provider right away if they get any symptoms of the following problems or these symptoms get worse.

Tecentriq can cause serious side effects, including:

Lung problems (pneumonitis)–signs and symptoms of pneumonitis may include new or worsening cough, shortness of breath, and chest pain
Liver problems (hepatitis)–signs and symptoms of hepatitis may include yellowing of the skin or the whites of the eyes, severe nausea or vomiting, pain on the right side of the stomach area (abdomen), drowsiness, dark urine (tea colored), bleeding or bruising more easily than normal, and feeling less hungry than usual
Intestinal problems (colitis)–signs and symptoms of colitis may include diarrhea (loose stools) or more bowel movements than usual, blood or mucus in stools or dark, tarry, sticky stools, and severe stomach area (abdomen) pain or tenderness
Hormone gland problems (especially the thyroid, adrenal glands, pancreas, and pituitary) –signs and symptoms that the hormone glands are not working properly may include headaches that will not go away or unusual headaches, extreme tiredness, weight gain or weight loss, dizziness or fainting, feeling more hungry or thirsty than usual, hair loss, changes in mood or behavior (such as decreased sex drive, irritability, or forgetfulness), feeling cold, constipation, the voice gets deeper, urinating more often than usual, nausea or vomiting, and stomach area (abdomen) pain
Problems in other organs–signs and symptoms may include severe muscle weakness, numbness or tingling in hands or feet, confusion, blurry vision, double vision, or other vision problems, changes in mood or behavior, extreme sensitivity to light, neck stiffness, eye pain or redness, skin blisters or peeling, chest pain, irregular heartbeat, shortness of breath, or swelling of the ankles
Severe infections–signs and symptoms of infection may include fever, cough, flu-like symptoms, pain when urinating, and frequent urination or back pain
Severe infusion reactions–signs and symptoms of infusion reactions may include chills or shaking, itching or rash, flushing, shortness of breath or wheezing, swelling of your face or lips, dizziness, fever, feeling like passing out, and back or neck pain
Getting medical treatment right away may help keep these problems from becoming more serious. A healthcare provider may treat patients with corticosteroid or hormone replacement medicines. A healthcare provider may delay or completely stop treatment with Tecentriq if patients have severe side effects.

Before receiving Tecentriq, patients should tell their healthcare provider about all of their medical conditions, including if they:

have immune system problems (such as Crohn’s disease, ulcerative colitis, or lupus); have had an organ transplant; have lung or breathing problems; have liver problems; have a condition that affects the nervous system (such as myasthenia gravis or Guillain-Barre syndrome); or are being treated for an infection
are pregnant or plan to become pregnant. Tecentriq can harm an unborn baby. Patients should tell their healthcare provider right away if they become pregnant or think they may be pregnant during treatment with Tecentriq. Females who are able to become pregnant:
a healthcare provider should do a pregnancy test before they start treatment with Tecentriq
they should use an effective method of birth control during their treatment and for at least 5 months after the last dose of Tecentriq
are breastfeeding or plan to breastfeed. It is not known if Tecentriq passes into the breast milk. Patients should not breastfeed during treatment and for at least 5 months after the last dose of Tecentriq
Patients should tell their healthcare provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of Tecentriq when used alone include:

feeling tired or weak
nausea
cough
shortness of breath
decreased appetite
The most common side effects of Tecentriq when used in lung cancer with other anti-cancer medicines include:

feeling tired or weak
nausea
hair loss
constipation
diarrhea
decreased appetite
The most common side effects of Tecentriq when used in triple-negative breast cancer with paclitaxel protein-bound include:

hair loss
tingling or numbness in hands or feet
feeling tired
nausea
diarrhea
low red blood cells (anemia)
constipation
cough
headache
low white blood cells
vomiting
decreased appetite
Tecentriq may cause fertility problems in females, which may affect the ability to have children. Patients should talk to their healthcare provider if they have concerns about fertility.

These are not all the possible side effects of Tecentriq. Patients should ask their healthcare provider or pharmacist for more information about the benefits and side effects of Tecentriq.

Report side effects to the FDA at 1-800-FDA-1088 or View Source Report side effects to Genentech at 1-888-835-2555.

Please visit View Source for the Tecentriq full Prescribing Information for additional Important Safety Information.

About Alecensa (alectinib)

Alecensa is a kinase inhibitor approved for the treatment of people with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test.

Alecensa U.S. Indication

Alecensa is a kinase inhibitor approved for the treatment of people with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test.

Important Safety Information

Everyone reacts differently to treatment with Alecensa. It’s important to know the most serious and most common side effects with Alecensa.

A doctor may lower the dose or stop treatment with Alecensa if any serious side effects occur. Patients taking Alecensa should contact their doctor right away if they have any of the following side effects.

Alecensa may cause serious side effects, including:

Liver problems (hepatotoxicity). Alecensa may cause liver injury. A doctor will do blood tests at least every 2 weeks for the first 3 months and as needed during treatment with Alecensa. Patients taking Alecensa should tell their doctor right away if they experience any of the following signs and symptoms:

Feeling tired
Feeling less hungry than usual
Yellowing of the skin or whites of the eyes
Dark urine
Itchy skin
Nausea or vomiting
Pain on the right side of stomach area
Bleeding or bruising more easily than normal
Lung problems. Alecensa may cause severe or life-threatening swelling (inflammation) of the lungs during treatment. Symptoms may be similar to those symptoms from lung cancer. Patients taking Alecensa should tell their doctor right away if they have any new or worsening symptoms, including:

Trouble breathing
Shortness of breath
Fever
Cough
Kidney problems. Alecensa may cause severe or life-threatening kidney problems. Tell your healthcare provider right away if you have a change in the amount or color of your urine, or if you get new or worsening swelling in your legs or feet.

Slow heartbeat (bradycardia). Alecensa may cause very slow heartbeats that can be severe. A doctor will check a patient’s heart rate and blood pressure during treatment with Alecensa. Patients taking Alecensa should tell their doctor right away if they feel dizzy, lightheaded, or faint during treatment with Alecensa. Patients taking Alecensa should tell their doctor if they take any heart or blood pressure medicines.

Muscle pain, tenderness, and weakness (myalgia). Muscle problems are common with Alecensa and can be severe. A doctor will do blood tests at least every 2 weeks for the first month and as needed during treatment with Alecensa. Patients taking Alecensa should tell their doctor right away if they have any new or worsening signs and symptoms of muscle problems, including unexplained muscle pain or muscle pain that does not go away, tenderness, or weakness.

Before taking Alecensa, patients should tell their doctor about all medical conditions, including if they:

Have liver problems
Have lung or breathing problems
Have a slow heartbeat
Are pregnant or plan to become pregnant. Alecensa can harm an unborn baby. Patients taking Alecensa should tell their doctor right away if they become pregnant during treatment with Alecensa or think they may be pregnant
Women who are able to become pregnant should use effective birth control during treatment with Alecensa and for one week after the final dose of Alecensa
Men who have female partners that are able to become pregnant should use effective birth control during treatment with Alecensa and for three months after the final dose of Alecensa
Are breastfeeding or plan to breastfeed. It is not known if Alecensa passes into breast milk. A patient should not breastfeed during treatment with Alecensa and for one week after the final dose of Alecensa. Patients should talk with their doctor about the best way to feed their baby during this time.
Patients taking Alecensa should tell their doctor about all the medicines they take, including prescription medicines, over-the-counter medicines, vitamins, and herbal supplements.

Patients taking Alecensa should avoid spending time in the sunlight during treatment with Alecensa and for seven days after the final dose of Alecensa. Patients taking Alecensa may burn more easily and get severe sunburns. Patients taking Alecensa should use sunscreen and lip balm with a SPF 50 or greater to help protect against sunburn.

The most common side effects of Alecensa include:

Tiredness
Constipation
Swelling in hands, feet, ankles, and eyelids
Low red blood cell count
These are not all of the possible side effects of Alecensa. For more information, patients should ask their doctor or pharmacist. Patients should call their doctor for medical advice about side effects.

On May 7, 2020 Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL) reported its first quarter 2020 financial results and highlights (Press release, Synta Pharmaceuticals, MAY 7, 2020, View Source [SID1234557348]):

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"Madrigal continued to make progress toward our clinical development and business objectives during the first quarter of 2020, despite challenges associated with the COVID-19 pandemic. Importantly, we continued to screen and enroll patients in our Phase 3 studies, MAESTRO-NASH and MAESTRO-NAFLD-1," stated Paul Friedman, M.D., Chief Executive Officer of Madrigal. "We are also pleased that Remy Sukhija has joined Madrigal as Senior Vice President and Chief Commercial Officer. Remy brings extensive commercial experience to Madrigal, having successfully launched multiple products in specialty, primary care and rare disease markets over his 27 years in pharmaceutical/biotech industry. His expertise in product launch, sales and marketing, and market access will be valuable as we continue to execute our Phase 3 clinical programs and continue to explore the market opportunity for resmetirom."

Becky Taub, M.D., CMO and President, Research & Development of Madrigal stated, "In response to the COVID-19 pandemic, and related direction from regulatory agencies, we rapidly implemented guidance to permit more flexible processes at those clinical sites impacted and allow patients to progress through the screening process or continue their enrollment in our Phase 3 NASH studies. Also, as a result of the pandemic and the resulting postponement or cancellation of two significant medical conferences, we were pleased to have the opportunity to announce new data from previous studies, which demonstrate that reductions in liver fat achieved by resmetirom predict NASH resolution and fibrosis improvement. Specifically, as we have showed, once daily oral 80 mg and 100 mg Phase 3 doses of resmetirom deliver at least 50% to more than 60% reductions in liver fat, respectively, and, based on new analyses of Phase 2 data, are associated with a statistically significant 64% NASH resolution (p<0.0001), of which >60% had fibrosis reduction."

Financial Results for the Three Months Ended March 31, 2020

As of March 31, 2020, Madrigal had cash, cash equivalents and marketable securities of $408.5 million, compared to $439.0 million at December 31, 2019. The decrease in cash and marketable securities resulted primarily from cash used in operations of $30.5 million.

Operating expenses were $38.0 million for the three month period ended March 31, 2020, compared to $18.1 million in the comparable prior year period.

Research and development expenses for the three month period ended March 31, 2020 were $33.4 million, compared to $12.4 million in the comparable prior year period. The increases are primarily attributable to the initiation of the Phase 3 clinical trial in NASH, an increase in head count, and an increase in non-cash stock compensation from stock option awards.

General and administrative expenses for the three month period ended March 31, 2020 were $4.6 million, compared to $5.7 million in the comparable prior year period. The decrease in general and administrative expenses for the latest three month period was due primarily to a decrease in non-cash stock compensation from stock option awards, which was partially offset by increases in other general and administrative expenses.

Interest income for the three month period ended March 31, 2020 was $1.9 million, as compared to $3.0 million in the comparable prior year period. The decrease in interest income for the latest three month period was due primarily to lower average principal balances in our investment accounts in 2020, and lower interest rates.

About Resmetirom (MGL-3196)

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

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

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

Analyses from the resmetirom Phase 2 NASH study demonstrate that the magnitude of liver fat reduction accurately predicts NASH resolution and liver fibrosis reduction and, specifically, that the resmetirom doses being used in Madrigal’s Phase 3 MAESTRO-NASH trial could achieve the level of fat reduction predictive of NASH resolution and fibrosis reduction [Madrigal COVID and ABSTRACT Press Release_20200414].

The Phase 3 MAESTRO-NASH trial is expected to enroll 900 patients with biopsy-proven NASH (fibrosis stage 2 or 3), randomized 1:1:1 to receive resmetirom 80 mg once a day, 100 mg once a day, or placebo. After 52 weeks of treatment a second biopsy is performed. The primary surrogate endpoint on biopsy will be NASH resolution, with at least a 2-point reduction in NAS (NASH Activity Score), and with no worsening of fibrosis. Two key secondary endpoints are liver fibrosis improvement of at least one stage, with no worsening of NASH, and lowering of LDL-cholesterol [ClinicalTrials.gov/NCT03900429].

A second 52-week Phase 3 multi-center, double-blind, randomized, placebo-controlled study of resmetirom, MAESTRO-NAFLD-1, was initiated in December 2019 in 700 patients with non-alcoholic fatty liver disease (NAFLD), presumed NASH, randomized 1:1:1 to receive resmetirom 80 mg once a day, 100 mg once a day, or placebo. MAESTRO-NAFLD-1 also includes a 100 mg resmetirom open label arm in up to 100 patients. Unlike MAESTRO-NASH, MAESTRO-NAFLD-1 is a non-biopsy study and represents a "real-life" NASH study. NASH or presumed NASH is documented using historical liver biopsy or non-invasive techniques including fibroscan and MRI-PDFF. Using non-invasive measures, MAESTRO-NAFLD-1 is designed to provide incremental safety information to support the NASH indication as well as provide additional data regarding clinically relevant key secondary efficacy endpoints to better characterize the potential clinical benefits of resmetirom on cardiovascular and liver related endpoints. These key secondary endpoints include LDL-cholesterol, apolipoprotein B and triglyceride (TG) lowering; reduction of liver fat as determined by magnetic resonance imaging, proton density fat fraction (MRI-PDFF); and reduction of PRO-C3, a NASH fibrosis biomarker. [ClinicalTrials.gov/NCT04197479] Additional secondary and exploratory endpoints will be assessed including reduction in liver enzymes, fibroscan scores and other fibrosis and inflammatory biomarkers. These and other data, including safety parameters, form the basis for potential subpart H submission to FDA for accelerated approval for the treatment of NASH. The original 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 and the study is expected to continue for up to 54 months to accrue and measure clinical events, most relevantly progression to cirrhosis.

About Resmetirom’s Potential to Confer Cardiovascular Risk Reduction in NASH patients

Additionally, resmetirom lowers multiple atherogenic lipids, including LDL cholesterol, apolipoprotein B, triglycerides, and lipoprotein (a), as demonstrated in Phase 2, a key differentiating factor compared with other NASH therapeutics. The magnitude of reduction of these lipids support a potential indication for treatment of hyperlipidemia in NASH patients and predicts a potential for benefit on cardiovascular (CV) events in NASH patients who die most frequently of CV, not liver disease.

Because of their diabetes, dyslipidemia, hypertension, obesity in concert with an inflamed, fatty liver, NASH patients, particularly those with advanced fibrosis, are at a substantially increased CV risk compared to the general population. Resmetirom’s ability to decrease liver fat, which is an independent risk factor for CV events, and resmetirom’s effect to reduce atherogenic lipids are being further evaluated in several key secondary endpoints in both MAESTRO Phase 3 clinical studies.

On May 7, 2020 CANbridge Pharmaceuticals Inc., a biopharmaceutical company developing innovative drug candidates to treat underserved medical conditions in China and other markets, reported that it has received marketing approval from China’s National Medical Products Administration (NMPA) for NERLYNX (neratinib) for the extended adjuvant treatment of adult patients with early stage HER2-positive breast cancer, following adjuvant trastuzumab-based therapy. NERLYNX was approved in Hong Kong in 2019 (Press release, CANbridge Life Sciences, MAY 7, 2020, View Source [SID1234557344]). CANbridge acquired the exclusive NERLYNX development and commercial rights from Puma Biotechnology, Inc. for China, Taiwan, Hong Kong and Macao in 2018.

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"We thank Puma for the cooperative relationship that, along with the responsiveness of the National Medical Products Administration, allowed us to achieve NERLYNX market approval just 18 months after submission, a testament to the CANbridge regulatory expertise," said James Xue, PhD, Founder, Chairman and CEO, CANbridge Pharmaceuticals Inc.. "Women in China with early stage breast cancer now have first-time access to oral adjuvant therapy."

"Reducing the risk of recurrence in HER2-positive early stage breast cancer patients remains paramount for Puma and our global partners," added Alan H. Auerbach, Chief Executive Officer and President of Puma Biotechnology. "Marketing approval in the region represents an important milestone as we continue to execute on our global commercial strategy. We thank and congratulate CANbridge for reaching this important milestone."

About HER2-Positive Breast Cancer

Approximately 20 to 25 percent of breast cancer tumors over-express the HER2 protein. HER2-positive breast cancer is often more aggressive than other types of breast cancer, increasing the risk of disease progression and death. Although research has shown that trastuzumab can reduce the risk of early stage HER2-positive breast cancer returning after surgery, up to 25% of patients treated with trastuzumab experience recurrence.

On May 7, 2020 Alector, Inc. (Nasdaq: ALEC), a clinical-stage biotechnology company pioneering immuno-neurology, reported that Shehnaaz Suliman, M.D., MBA, M.Phil., president and chief operating officer of Alector, will present at the Bank of America Securities Virtual Health Care Conference on Wednesday, May 13, 2020, at 3:40 p.m. ET (Press release, Alector, MAY 7, 2020, View Source [SID1234557342]).

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A live webcast of the presentation will be available on the "Events & Presentations" page within the Investors section of the Alector website at View Source A replay will be available on the Alector website for 30 days following the event.

On May 7, 2020 Aeglea BioTherapeutics, Inc. (NASDAQ:AGLE), a clinical-stage biotechnology company developing a new generation of human enzyme therapeutics as innovative solutions for rare and other high-burden diseases, reported its first quarter 2020 financial results, and provided recent corporate and program highlights (Press release, Aeglea BioTherapeutics, MAY 7, 2020, View Source [SID1234557331]).

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"These past few months have brought unique challenges as we navigate the impact of COVID-19, and reminds us all of the critical need for healthcare innovation and new medicines. These needs are all too familiar for people with rare diseases, like Arginase 1 Deficiency, where adequate treatment options are often not available," said Anthony Quinn, M.B Ch.B, Ph.D., president and chief executive officer of Aeglea. "With our recently completed financing, we have the resources to advance our pegzilarginase program for Arginase 1 Deficiency through regulatory submission and potential FDA approval. With the recent approval of our Clinical Trial Application for ACN00177 for the treatment of Homocystinuria, the company is positioned to bring forward its second clinical-stage human enzyme – both with the potential to be transformative solutions for rare genetic disorders."

Recent Highlights & COVID-19 Update

Pegzilarginase in Arginase 1 Deficiency

Aeglea is working with treating physicians to implement individual treatment plans and potentially developing a home healthcare option for patients enrolled in the Phase 3 PEACE trial.
To date, most enrolled patients have continued to receive treatment. The Company is developing a plan to analyze results for patients that are missing data points. The Phase 3 PEACE trial protocol is designed in such a way that a patient may miss a few doses without being disqualified from the trial.
The supply chain has not experienced any significant impact at this time and the Company currently has sufficient supply available for completion of its ongoing clinical trials.
The Company expects to complete enrollment of its Phase 3 PEACE trial in the third quarter of 2020 and to provide topline data in the first quarter of 2021.
ACN00177 in Homocystinuria

In April, Aeglea announced the approval of its Clinical Trial Application (CTA) by the United Kingdom’s Medicines and Healthcare Products Regulatory Agency (MHRA) for ACN00177, a novel engineered human enzyme therapy designed to treat Homocystinuria, a serious metabolic disorder characterized by elevated plasma homocysteine which leads to a wide range of life-altering complications and reduced life expectancy.
The Company continues its patient identification and administrative activities to quickly move forward with dosing patients once trial sites are able to initiate clinical trials.
While Aeglea continues to prepare to initiate a Phase 1/2 trial for ACN00177 in the second quarter of 2020, the timing will depend on determination by individual sites that each is ready to open for recruitment in light of COVID-19; the Company’s priorities at this time are to avoid further overburdening hospital staff and to minimize the risk of trial participants exposure to COVID-19.
Corporate Highlights

In April, the Company strengthened its financial position with a public offering resulting in gross proceeds of $138 million, which extended its cash runway through 2022.
The Company implemented policies and practices to protect the health and wellbeing of the Company’s employees and communities, including asking employees to work from home and implementing a work rotation for essential lab employees.
Aeglea suspended all business travel and transitioned all meetings, including conference attendance and industry events, to virtual meetings.
First Quarter 2020 Financial Results

As of March 31, 2020, Aeglea had available cash, cash equivalents, marketable securities and restricted cash of $50.5 million. In addition, in April 2020 the Company raised approximately $129.6 million in net proceeds from a public offering. Based on Aeglea’s current operating plan, and taking into account the net offering proceeds, management believes it has sufficient capital resources to fund anticipated operations through 2022.

Research and development expenses totaled $14.6 million for the first quarter of 2020 and $14.4 million for the first quarter of 2019. The increase was primarily associated with investing in manufacturing and pre-commercial activities for Aeglea’s lead product candidate, pegzilarginase; ramp-up in toxicology, nonclinical studies, and manufacturing activities for ACN00177 in Homocystinuria; and personnel-related expenses. The increase was offset by a decrease in clinical development expenses as a result of completing a Phase 1/2 clinical trial in patients with Arginase 1 Deficiency, a Phase 1 clinical trial in patients with advanced solid tumors, and concluding enrollment of a Phase 1/2 combination trial in patients with small cell lung cancer.

General and administrative expenses totaled $4.5 million for the first quarter of 2020 and $3.3 million for the first quarter of 2019. This increase was primarily due to additional employee headcount, ramping up commercial capabilities, and additional facilities to support company growth.

Net loss totaled $18.7 million and $17.2 million for the first quarter of 2020 and 2019, respectively, with non-cash stock compensation expense of $1.3 million and $1.1 million for the first quarter of 2020 and 2019, respectively.

About Pegzilarginase in Arginase 1 Deficiency

Pegzilarginase is an enhanced human arginase that enzymatically lowers levels of the amino acid arginine. Aeglea is developing pegzilarginase for the treatment of patients with Arginase 1 Deficiency (ARG1-D), a rare debilitating disease presenting in childhood with persistent hyperargininemia, severe progressive neurological abnormalities and early mortality. Pegzilarginase is intended for use as an enzyme therapy to reduce elevated blood arginine levels in patients with ARG1-D. Aeglea’s Phase 1/2 and Phase 2 open-label extension data for pegzilarginase in patients with ARG1-D demonstrated clinical improvements and sustained lowering of plasma arginine. The Company’s single, global pivotal Phase 3 PEACE trial is designed to assess the effects of treatment with pegzilarginase versus placebo over 24 weeks with a primary endpoint of plasma arginine reduction.

About ACN00177 in Homocystinuria

Aeglea is developing ACN00177 for the treatment of patients with cystathionine beta synthase (CBS) deficiency, also known as Classical Homocystinuria. Homocysteine accumulation plays a key role in multiple progressive and serious disease-related complications, including thromboembolic vascular events, skeletal abnormalities including severe osteoporosis, developmental delay, intellectual disability, lens dislocation and severe near-sightedness. ACN00177 has been designed as a novel recombinant human enzyme, which degrades the amino acid homocysteine and its related homocystine dimer. With this mechanism, ACN00177 is intended to lower the abnormally high blood levels of homocysteine in patients with Homocystinuria. Preclinical data demonstrated that ACN00177 improved important disease-related abnormalities and survival in a mouse model of Homocystinuria. The Company received approval from the United Kingdom’s Medicines and Healthcare Products Regulatory Agency (MHRA) for its Clinical Trial Application (CTA) and continues to prepare to initiate a Phase 1/2 trial in the second quarter of 2020.