On May 8, 2019 Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL) reported its first quarter 2019 financial results and highlights (Press release, Synta Pharmaceuticals, MAY 8, 2019, View Source [SID1234535926]):

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"Madrigal continued to make significant progress in the first quarter of 2019, initiating a Phase 3 study of MGL-3196 (resmetirom) in patients with biopsy-proven non-alcoholic steatohepatitis (NASH) and liver fibrosis (MAESTRO-NASH)," stated Paul Friedman, M.D., Chief Executive Officer of Madrigal. "We also look forward to advancing our planned Phase 3 clinical trial in patients with NAFLD/NASH and dyslipidemia in the latter half of this year."

Becky Taub, M.D., CMO and Executive VP, Research & Development of Madrigal added, "An experienced group of NASH investigators and clinical sites around the world are participating in MAESTRO-NASH, and we are encouraged regarding timely enrollment. We believe the pleiotropic effects of resmetirom provide the potential to resolve NASH and improve liver fibrosis, and in addition, by reducing the levels of multiple atherogenic lipids and liver fat, also reduce cardiovascular risk."

Additional information about Madrigal’s Phase 3 study in patients with NASH [NCT03900429] can be obtained at www.clinicaltrials.gov.

Financial Results for the Three Months Ended March 31, 2019

As of March 31, 2019, Madrigal had cash, cash equivalents and marketable securities of $477.8 million, compared to $483.7 million at December 31, 2018. Cash used in operating activities during the first quarter of 2019 was $6.5 million.

Operating expenses were $18.1 million for the three month period ended March 31, 2019, compared to $7.1 million in the comparable prior year period.

Research and development expenses for the three month period ended March 31, 2019 were $12.4 million compared to $5.2 million in the comparable prior year period. The increase is primarily attributable to additional activities related to initiation of our Phase 3 clinical trial in NASH, including an increase in headcount and increased non-cash stock compensation from stock option awards.

General and administrative expenses for the three month period ended March 31, 2019 were $5.7 million compared to $1.9 million in the comparable prior year period. The

increase is due primarily to higher non-cash stock compensation expense from stock option awards.

Interest income for the three month period ended March 31, 2019 was $3.0 million compared to $705 thousand in the comparable prior year period. The change in interest income was due primarily to a higher average principal balance in our investment portfolio in 2019, and increased interest rates.

About resmetirom (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 resmetirom is the first orally administered, small-molecule, liver- directed, truly β-selective THR agonist.

Based on the positive Phase 2 clinical study results in patients with NASH (Phase 2 36-Week Results Press Release), Madrigal recently announced the initiation of a Phase 3 multinational, double-blind, randomized, placebo-controlled study of resmetirom in patients with non-alcoholic steatohepatitis (NASH) and fibrosis to resolve NASH and reduce progression to cirrhosis and/or hepatic decompensation (Phase 3 Initiation Press Release and ClinicalTrials.gov NCT03900429). Additionally, in both the NASH Phase 2 study, and a second positive Phase 2 clinical study in patients with heterozygous familial hypercholesterolemia (Phase 2 HeFH Results Press Release), significant reductions in multiple atherogenic lipids were observed. As a result, Madrigal is designing a Phase 3 study intended to treat the prevalent dyslipidemias in NAFLD and NASH patients and improve the fatty liver phenotype in this population.

On May 8, 2018 Constellation Pharmaceuticals, Inc. (Nasdaq: CNST), a clinical-stage biopharmaceutical company using its expertise in epigenetics to discover and develop novel therapeutics, reported its first-quarter 2019 financial results (Press release, Constellation Pharmaceuticals, MAY 8, 2019, View Source [SID1234535942]).

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"2019 is a year of data for Constellation," said Jigar Raythatha, President and Chief Executive Officer of Constellation Pharmaceuticals. "We look forward to an exciting year ahead, as we continue to see strong enrollment trends and expect multiple clinical readouts throughout the year for both CPI-0610 in myelofibrosis (MF) and CPI-1205 in prostate cancer.

"We look forward to presenting an interim update of data from the Phase 2 MANIFEST clinical trial for CPI-0610 in a poster presentation at ASCO (Free ASCO Whitepaper) and an oral presentation at EHA (Free EHA Whitepaper) in June," Mr. Raythatha continued. "We believe these data will support the view that CPI-0610 has the potential to be a disease-modifying agent in MF. Additionally, we expect to provide further data readouts on both CPI-0610 and CPI-1205 in the second half of 2019.

"Our vision is to become a late-stage oncology development company in 2020, with an exciting pipeline of development and discovery programs that have the potential to bring important new medicines to underserved cancer patients," Mr. Raythatha concluded.

Medical Presentations

Constellation plans to present a poster providing an interim update of data from the MANIFEST clinical trial of CPI-0610 at the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting at 9:00 AM EDT/8:00 CDT on June 3. In addition, Dr. Ronald Hoffman of Mt. Sinai Health System, an investigator in the MANIFEST trial, will make an oral presentation providing an interim update of data at the European Hematology Association (EHA) (Free EHA Whitepaper) annual meeting at 12:15 PM CEST/6:15 AM EDT on June 15. Data to be presented at these events were generated from 44 patients enrolled as of April 17, 2019. Twelve patients received 24-week assessments and 16 patients received 12-week assessments. The Company plans to report data for these patients based on the following parameters: spleen volume reduction; total symptom score improvement; hematologic parameters such as increased hemoglobin and conversion to transfusion independence; bone marrow fibrosis improvement; and safety.

Investor Event

The Company will also host an analyst/investor meeting, with an accompanying conference call and webcast, to discuss the interim update of data at Hyatt McCormick Place in Chicago at 8:00 AM EDT/7:00 AM CDT on June 4. The agenda of the meeting will include an overview of MF, the potential impact of CPI-0610 on MF, review of the interim update of data from MANIFEST, and a panel discussion with Dr. Srdan Verstovsek of MD Anderson Cancer Center, an investigator in the MANIFEST trial, and Dr. Raajit Rampal of Memorial Sloan Kettering Cancer Center. Additional details about this event will be announced at a later date.

Recent News

Provided data update of MANIFEST clinical trial at J.P. Morgan Healthcare Conference. In a press release on January 3 and a presentation at the J.P. Morgan Healthcare Conference on January 9, Constellation provided an interim update of data on the Phase 2 MANIFEST clinical trial of CPI-0610. As disclosed in that presentation, each of the first four ruxolitinib-resistant MF patients in MANIFEST remained on study as of December 10, 2018. Two patients were treated with a combination of CPI-0610 and ruxolitinib for over 16 months, and two patients were treated with CPI-0610 monotherapy for over 12 months. Each of these four patients showed a reduction in spleen volume, symptom improvement, and an increased hemoglobin level. One of the combination therapy patients, who was transfusion dependent before therapy, converted to being transfusion independent after CPI-0610 was added to the ongoing regimen. Additionally, bone marrow biopsies before and after treatment were analyzed for the two patients on monotherapy, and both demonstrated a one-grade improvement in bone marrow fibrosis score and associated improvements in hemoglobin and platelets. Taken together, these results suggest that CPI-0610 may be modifying the underlying course of the disease in these ruxolitinib-resistant MF patients.

Presented ProSTAR results at AACR (Free AACR Whitepaper). On April 1, Constellation presented results from the Phase 1b portion of the ProSTAR clinical trial of CPI-1205 at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting. These results showed clinical activity in subsets of a heterogeneous population of advanced mCRPC patients in combination with either abiraterone or enzalutamide. All PSA responses seen in the trial were ≥80%, deeper than the ≥50% reduction endpoint in the trial. The majority of patients with measurable lesions achieved durable disease control during the study. For more details, please review the poster on our website here.

The Company initiated the Phase 2 portion of the trial in late 2018 to better define the patient populations most likely to benefit from CPI-1205. The Company looks forward to reporting initial Phase 2 data in the second half of 2019.
Expanded Board of Directors. In February, Constellation announced the appointment of Dr. Scott Braunstein to its Board of Directors. Dr. Braunstein brings a track record of growing emerging and established biopharmaceutical companies as a board member, pharmaceutical executive, and investor.

Enhanced Management Team. Also in February, Constellation announced the appointment of Jessica Christo as Senior Vice President and Chief Product Development Officer. Ms. Christo has 25 years of product development experience in the biopharmaceutical industry. Most recently, she was Senior Vice President of Development Operations at Verastem Oncology, where she had broad clinical and regulatory responsibilities and contributed to the approval of COPIKTRATM.
First Quarter 2019 Financial Results

Cash, cash equivalents, and marketable securities as of March 31, 2019, increased 1.0% compared to December 31, 2018, to $115.8 million due to proceeds from a $20 million term loan led by Hercules Capital, which approximately offset operating expenses in the quarter.

Research and development (R&D) expenses increased 58.8% year over year to $15.7 million in the first quarter of 2019 mainly due to increased clinical trial expenses.

General and administrative (G&A) expenses grew 92.3% year over year to $4.4 million in the first quarter of 2019, primarily due to personnel-related and facility-related costs in connection with expanding the support functions of a multi-candidate clinical-stage company, as well as costs associated with operating as a public company.

The net loss attributable to common stockholders increased 60.5% year over year to $19.4 million mainly due to increases in G&A and R&D expenses. The net loss per share attributable to common stockholders decreased 94.0% to $0.75 per share for the first quarter of 2019 due to an increase in shares outstanding as a result of the initial public offering in 2018 and conversion of preferred stock to common stock.
Financial Guidance

The Company expects that cash, cash equivalents, and marketable securities as of March 31, 2019, will fund operating expenses and capital expenditure requirements into the third quarter of 2020.

Anticipated Milestones

The Company anticipates achieving the following milestones during 2019:

First Half 2019

Provide an interim update of data from the MANIFEST Phase 2 trial of CPI-0610 at ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper)
Complete an investigational new drug (IND) filing for CPI-0209
Second Half 2019

Provide an interim update of data from the Phase 2 portion of the ProSTAR trial for CPI-1205
Provide an additional data update from the MANIFEST trial for CPI-0610

On May 8, 2019 Audentes Therapeutics, Inc. (Nasdaq: BOLD), a leading AAV-based genetic medicines company focused on developing and commercializing innovative products for serious rare neuromuscular diseases, reported that it will participate in the Bank of America Merrill Lynch Health Care Conference, taking place May 15-17 in Las Vegas, NV (Press release, Audentes Therapeutics, MAY 8, 2019, View Source [SID1234535959]).

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Matthew R. Patterson, Chairman and Chief Executive Officer, will participate in the following events during the conference:

Fireside Chat
Wednesday, May 15, 2019, at 3:40 pm PDT

Panel Discussion: Gene Therapy Landscape
Wednesday, May 15, 2019, at 4:20 pm PDT

To access a live webcast of the fireside chat, please visit the Events & Presentations page within the Investors + Media section of the Audentes website. A replay of the live webcast will be available on the Audentes website for approximately 30 days following the conference.

On May 8, 2019 Sunesis Pharmaceuticals, Inc. (Nasdaq: SNSS) reported financial results for the first quarter ended March 31, 2019. Loss from operations for the three months ended March 31, 2019 was $5.7 million (Press release, Sunesis, MAY 8, 2019, View Source [SID1234535991]). As of March 31, 2019, cash and cash equivalents totaled $24.8 million.

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"We continue our focus on the execution of the Phase 1b/2 trial of vecabrutinib and are excited to announce that we have completed the safety evaluation period for the 100 mg cohort, enabling us to advance the trial into the 200 mg cohort," said Dayton Misfeldt, Interim Chief Executive Officer of Sunesis. "To date, vecabrutinib appears to be well tolerated in the context of disease, and we will be providing a clinical update on the study at the European Hematology Association (EHA) (Free EHA Whitepaper) annual meeting in June."

Mr. Misfeldt continued, "Underscoring our clinical progress is a strengthened financial position. We began the first quarter by completing an equity offering with leading biotechnology investors, extending our cash runway through important clinical milestones, and just last month we announced the refinancing of our debt on favorable terms through an agreement with Silicon Valley Bank, a vote of confidence in our pipeline and its potential from a premier debt provider for life science companies."

Recent Highlights

Advancement into 200 mg Cohort. The Company has opened the 200 mg cohort in the Phase 1b/2 trial of its non-covalent BTK inhibitor vecabrutinib in adults with relapsed/refractory chronic lymphocytic leukemia (CLL) and other B-cell malignancies.

$5.5 Million Loan with Silicon Valley Bank. In April 2019, the Company entered into a $5.5 million loan agreement with Silicon Valley Bank. The new agreement allows the company to retire its existing loan and defer any principal repayment on the new loan for more than 18 months. The new facility includes interest-only payments through 2020, with principal repayment over 24 months beginning in 2021, as well as a lower interest rate than the previous loan. The loan was used for the repayment of the Company’s existing indebtedness.

Completion of $20 Million Financing. In January, Sunesis completed an equity financing with net proceeds of approximately $18.6 million. The financing attracted participation from leading biotechnology investors and will allow Sunesis to advance vecabrutinib through important clinical milestones as the ongoing dose-escalation study explores potentially active dose levels.

Financial Highlights

Cash and cash equivalents totaled $24.8 million as of March 31, 2019, as compared to $13.7 million as of December 31, 2018. The increase of $11.1 million was primarily due to $18.6 million

net proceeds from issuance of common and preferred stock, offset by $6.1 million net cash used in operating activities and $1.4 million principal payment on the Loan Agreement with Western Alliance Bank and Solar Capital Ltd.

Research and development expense was $3.2 million for the three months ended March 31, 2019, as compared to $4.0 million for the same period in 2018. The decrease of $0.8 million between the comparable three-month periods was primarily due to a $0.4 million decrease in salary and personnel expenses due to lower headcount and a $0.4 million decrease in professional services related to higher expenses incurred in the first quarter of 2018 for the start-up cost of Phase 1b/2 trial for vecabrutinib.

General and administrative expense was $2.4 million for the three months ended March 31, 2019, as compared to $3.4 million for the same period in 2018. The decrease of $1.0 million between the comparable three-month periods was primarily due to a $0.7 million decrease in salary and personnel expenses due to lower headcount and a $0.4 million decrease in professional services expenses due in part to lower vosaroxin patent expenses.

Interest expense was $0.3 million for the three months ended March 31, 2019 and 2018. The interest expenses from both periods resulted from payments on our Loan Agreement with Western Alliance Bank and Solar Capital Ltd.

Cash used in operating activities was $6.1 million for the three months ended March 31, 2019, as compared to $6.6 million for the same period in 2018. Net cash used in the three months ended March 31, 2019 resulted primarily from the net loss of $5.9 million, partially offset by adjustments for non-cash items of $0.5 million and changes in operating assets and liabilities of $0.7 million. Net cash used in the three months ended March 31, 2018, resulted primarily from the net loss of $7.3 million and changes in operating assets and liabilities of $0.2 million, offset by net adjustments for non-cash items of $0.9 million.

Loss from operations was $5.7 million for the three months ended March 31, 2019, as compared to $7.1 million for the same period in 2018. Net loss was $5.9 million for the three months ended March 31, 2019, as compared to $7.3 million for the same period in 2018.

Conference Call Information

Sunesis will host a conference today at 4:30 p.m. Eastern Time. The call can be accessed by dialing (844) 296-7720 (U.S. and Canada) or (574) 990-1148 (international) and entering passcode 1396684. To access the live audio webcast, or the subsequent archived recording, visit the "Investors and Media – Calendar of Events" section of the Sunesis website at www.sunesis.com. The webcast will be recorded and available for replay on the company’s website for two weeks.

On May 8, 2019 Arvinas, Inc. (Nasdaq: ARVN), a biopharmaceutical company creating a new class of therapies that degrades disease-causing proteins, reported financial results for the first quarter of 2019 and provided a corporate update (Press release, Arvinas, MAY 8, 2019, View Source [SID1234535898]).

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"The first quarter of 2019 was Arvinas’ first quarter as a clinical-stage company and we remain laser-focused on moving our clinical and preclinical programs ahead," said John Houston, Ph.D., Chief Executive Officer at Arvinas. "We are excited that our Phase 1 clinical trial of ARV-110 for the treatment of men with metastatic castration-resistant prostate cancer is underway and look forward to sharing preliminary clinical data regarding the trial in the second half of 2019."

Ian Taylor, Ph.D., Chief Scientific Officer at Arvinas, added, "The ARV-110 clinical trial is a milestone for patients affected by diseases that may be addressable by targeted protein degradation. Our second PROTAC protein degrader, ARV-471, remains on-track to enter the clinic in the third quarter as a potential treatment for patients with locally-advanced or metastatic breast cancer. Our recent progress has excited us further about what we can achieve with our PROTAC protein degrader platform and its potential to significantly improve the lives of patients."

Business Highlights and Recent Developments

Began dosing patients in our first clinical trial, a Phase 1 clinical trial of ARV-110, which will evaluate the safety and tolerability of ARV-110 in patients with metastatic castration-resistant prostate cancer (mCRPC) who have progressed on standard of care therapies. We anticipate preliminary data from the study in the second half of 2019 and believe ARV-110 is the first in a new class of targeted protein degraders to enter human clinical trials.
Completed our initial public offering (IPO) in October 2018, issuing an aggregate of 7,700,482 shares of common stock, including 200,482 additional shares of common stock upon the exercise, in part by the underwriters, of their option to purchase additional shares at a public offering price of $16.00 per share. The company received aggregate gross proceeds of approximately $123.2 million.
Anticipated Milestones and Expectations

Present preliminary safety, tolerability and pharmacokinetic data from the Phase 1 clinical trial of ARV-110 in the second half of 2019.
Initiate a Phase 1 clinical trial of ARV-471 in patients with locally advanced or metastatic ER-positive / HER2-negative breast cancer in the third quarter of 2019 and share preliminary clinical data in 2020.
Discuss our neuroscience strategy and present preclinical data from our tau program in the second half of 2019.
Financial Guidance

Based on its current operating plan, Arvinas expects its cash, cash equivalents, and marketable securities as of March 31, 2019 will be sufficient to fund its operating expenses and capital expenditure requirements into the first half of 2021.

First Quarter Financial Highlights

Cash, Cash Equivalents, and Marketable Securities Position: As of March 31, 2019, cash, cash equivalents, and marketable securities were $175.0 million as compared to $187.8 million as of December 31, 2018. The decrease related to cash used to fund operations of $15.5 million offset by cash received from a collaborator of $2.7 million.

Research and Development Expenses: Research and development expenses were $14.2 million for the quarter ended March 31, 2019, as compared to $7.1 million for the quarter ended March 31, 2018. The increase in research and development expenses for the quarter primarily related to expenses associated with the initiation of our Phase 1 clinical trial of ARV-110 and IND-enabling expenses associated with ARV-471 as well as increased personnel and other expenses related to our platform research and exploratory programs research.

General and Administrative Expenses: General and administrative expenses were $5.6 million for the quarter ended March 31, 2019, as compared to $1.2 million for the quarter ended March 31, 2018. The increase in general and administrative expenses for the quarter was primarily related to increased employee expenses and other compliance costs associated with becoming a public company in the fourth quarter of 2018.

Revenues: Revenue was $4.0 million for the quarter ended March 31, 2019, as compared to $4.1 million for the quarter ended March 31, 2018. Revenues are generated primarily from the license and rights to technology fees and research and development activities related to the collaboration and license agreement with Pfizer that was initiated in January 2018 and the amended and restated option, license and collaboration agreement with Genentech that was initiated in November 2017.

Net Loss: Net loss was $14.4 million for the quarter ended March 31, 2019, as compared to $4.2 million for the quarter ended March 31, 2018. The increase in net loss for the quarter ended March 31, 2019 was primarily due to increased research and development expenses and increased general and administrative expenses.

About ARV-110
ARV-110 is an orally-bioavailable PROTAC protein degrader designed to selectively target and degrade androgen receptor protein (AR). ARV-110 is being developed as a potential treatment for men with metastatic castration-resistant prostate cancer (mCRPC). ARV-110 has demonstrated activity in preclinical models of AR mutation or overexpression, both common mechanisms of resistance to currently available AR-targeted therapies. Arvinas believes the differentiated pharmacology of ARV-110, including its iterative activity, has the potential to translate into improved clinical outcomes for patients.

About ARV-471
ARV-471 is an orally-bioavailable PROTAC protein degrader designed to target the estrogen receptor (ER) for the treatment of patients with locally-advanced or metastatic ER-positive / HER2-negative breast cancer. A Phase 1 clinical trial for ARV-471 in patients with locally-advanced or metastatic ER-positive / HER2-negative breast cancer is expected to begin in the third quarter of 2019 and preliminary clinical data is expected in 2020.