On March 5, 2020 BioCryst Pharmaceuticals, Inc. (Nasdaq:BCRX) reported financial results for the fourth quarter and full year ended December 31, 2019, and provided a corporate update (Press release, BioCryst Pharmaceuticals, MAR 5, 2020, View Source [SID1234555195]).

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"2020 is off to a strong start, with NDAs accepted and approvals lined up later this year in the U.S. and Japan, and continued progress with our oral Factor D program as we approach proof of concept data in PNH patients in the second quarter of the year," said Jon Stonehouse, president and chief executive officer of BioCryst.

"We are hearing increasing excitement from both HAE patients and physicians about the availability of an oral option to manage their disease, and we are attracting outstanding commercial talent to bring this new medicine to patients," Stonehouse added.

Upcoming Key Milestones

HAE Program – Berotralstat (BCX7353)

Submit Marketing Authorization Application (MAA) for oral, once-daily berotralstat for the prevention of hereditary angioedema (HAE) attacks with the European Medicines Administration (EMA) (Q1 2020)

Approval and launch of oral, once-daily berotralstat in Japan (2H 2020)

Approval and launch of oral, once-daily berotralstat in U.S. (December 3, 2020 PDUFA date)
Complement Oral Factor D Inhibitor Program – BCX9930

Report data from a proof of concept study in paroxysmal nocturnal hemoglobinuria (PNH) patients receiving oral BCX9930 (2Q 2020)
ALK-2 Inhibitor Program – BCX9250

Report data from Phase 1 clinical trial of BCX9250, an oral ALK-2 kinase inhibitor for treatment of fibrodysplasia ossificans progressiva (FOP), in healthy subjects (2H 2020)
Coronavirus Antiviral Update – Galidesivir (BCX4430)
Galidesivir is a broad-spectrum antiviral currently being developed in a Phase 2 clinical trial (Yellow Fever) under contracts with the National Institute of Allergy and Infectious Diseases (NIAID) and U.S. Department of Health and Human Services (HHS).

Galidesivir has been shown to be active against more than 20 RNA viruses in nine different families, including coronaviruses. In Phase 1 trials in healthy volunteers, galidesivir was generally safe and well tolerated.

The company is in active dialogue with relevant U.S. public health authorities as they assess potential approaches to treat and prevent COVID-19, and whether galidesivir could be useful.

Recent Corporate Developments

On March 5, 2020, the company announced it had dosed its first PNH patients in a proof of concept study with its oral Factor D inhibitor, BCX9930.

On March 3, 2020, the company announced it will present at the Barclays Global Healthcare Conference in Miami Beach, Florida on Tuesday, March 10, 2020. The company’s presentation time has been changed to 8:30 a.m. ET that day.

On February 27, 2020, the company announced it will present abstracts with new data on oral, once-daily berotralstat (BCX7353) at the upcoming annual meeting of the American Academy of Allergy, Asthma & Immunology (AAAAI) March 13-16 in Philadelphia.

On February 25, 2020 the company announced the appointment of former Pfizer CFO, Alan G. Levin, to its Board of Directors.

On February 18, 2020, the company announced that the U.S. Food and Drug Administration (FDA) had accepted and filed its new drug application (NDA) for the approval of oral, once-daily berotralstat (BCX7353) for the prevention of hereditary angioedema (HAE) attacks. The Prescription Drug User Fee Act (PDUFA) date for the NDA is December 3, 2020. In the NDA filing acceptance letter, the FDA stated that they are not currently planning to hold an advisory committee meeting to discuss the NDA.

On February 3, 2020, the company announced that it had submitted a new drug application (JNDA) to the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) for approval of oral, once-daily berotralstat for the prophylactic treatment of HAE.

On January 15, 2020 the company announced the appointments of Charles Gayer as chief commercial officer and Allen Hodge as vice president and general manager for the United States.

On January 12, 2020, the company announced that the APeX-J trial in Japan met its primary endpoint (p=0.003) for prevention of HAE attacks, and berotralstat was safe and generally well-tolerated.

On December 11, 2019, the company announced it had submitted a new drug application to the FDA for approval of oral, once-daily berotralstat (BCX7353) for the prevention of HAE attacks.

On November 18, 2019, the company announced it had completed a public offering of common stock and received gross proceeds of approximately $63.3 million. In addition, the company completed a pre-funded warrants transaction on November 21, 2019 that provided gross proceeds of $19.9 million.
Fourth Quarter 2019 Financial Results

For the three months ended December 31, 2019, total revenues were $39.7 million, compared to $2.7 million in the fourth quarter of 2018. The increase was primarily due to the recognition of $20.1 million of the $22.0 million upfront payment from Torii for commercialization rights in Japan for berotralstat for the prevention of HAE attacks, and $13.9 million of RAPIVAB (peramivir injection) product sales under our procurement contract with the Centers for Disease Control.

Research and development (R&D) expenses for the fourth quarter of 2019 increased to $26.8 million from $23.4 million in the fourth quarter of 2018, primarily due to increased spending on the company’s complement-mediated diseases program and other preclinical development initiatives.

Selling, general and administrative (SG&A) expenses for the fourth quarter of 2019 increased to $10.5 million, compared to $4.5 million in the fourth quarter of 2018. The increase was primarily due to increased spending on commercial activities and medical affairs to support the U.S. commercial launch of berotralstat in 2020 and, to a lesser extent, legal expenses associated with our ongoing arbitration.

Interest expense was $3.1 million in the fourth quarter of 2019, compared to $2.4 million in the fourth quarter of 2018 and was associated with an increase in the outstanding balance of the company’s secured credit facility in February 2019 and increased interest expense associated with the company’s non-recourse notes payable.

Net loss for the fourth quarter of 2019 was $2.6 million, or $0.02 per share, compared to a net loss of $27.4 million, or $0.25 per share, for the fourth quarter of 2018.

Cash, cash equivalents and investments totaled $137.8 million at December 31, 2019, and reflect an increase from $128.4 million at December 31, 2018. Cash and investments reflect the proceeds from a November 2019 equity offering and a prefunded warrants transaction, as well as a $22.0 million upfront payment from Torii, offset by normal operating expenses. Net proceeds from these transactions yielded just over $100 million in capital in the fourth quarter and provide the company sufficient capital to fund the launch of berotralstat in the United States as well as its other planned operations through 2020. Operating cash use for the fourth quarter of 2019 was $33.5 million, and for the full year of 2019 was $111.4 million.

Full Year 2019 Financial Results

For the full year ended December 31, 2019, total revenues were $48.8 million, compared to $20.7 million in the full year ended December 31, 2018. The increase was primarily due to the recognition of $20.1 million of the $22.0 million upfront payment from Torii, $13.9 of RAPIVAB product sales under our procurement contract and $3.7 million of peramivir product sales to our licensing partners. The increase in revenues was partially offset by the recognition of $12.0 million of peramivir milestones recognized in 2018 that did not recur in 2019.

R&D expenses in 2019 increased to $107.1 million from $84.9 million in 2018, primarily due to increased spending on the company’s complement-mediated diseases program and other preclinical development initiatives.

SG&A expenses in 2019 increased to $37.1 million, compared to $29.5 million in 2018. The increase was primarily due to increased spending on commercial activities and medical affairs to support the U.S. commercial launch of berotralstat in 2020. The increased commercial and medical affairs costs were partially offset by the non-recurring merger-related costs associated with the company’s terminated merger with Idera and a $4.9 million reserve for collectability of the EMA approval milestone of peramivir.

Interest expense was $11.9 million in 2019, compared to $9.2 million in 2018. The increase was associated with an increase in the outstanding balance of the company’s secured credit facility in February 2019 and increased interest expense associated with the company’s non-recourse notes payable.

Net loss for 2019 was $108.9 million, or $0.94 per share, compared to a net loss of $101.3 million, or $0.98 per share, for 2018.

Financial Outlook for 2020

BioCryst expects full year 2020 net operating cash use to be in the range of $125 to $150 million, and its operating expenses to be in the range of $135 to $160 million. The company’s operating expense range excludes equity-based compensation expense due to the difficulty in reliably projecting this expense, as it is impacted by the volatility and price of the company’s stock, as well as by the vesting of the company’s outstanding performance-based stock options.

Conference Call and Webcast

BioCryst management will host a conference call and webcast at 8:30 a.m. ET today to discuss the financial results and provide a corporate update. The live call may be accessed by dialing 877-303-8027 for domestic callers and 760-536-5165 for international callers and using conference ID # 7351587. A live webcast of the call and any slides will be available online at the investors section of the company website at www.biocryst.com. A telephone replay of the call will be available by dialing 855-859-2056 for domestic callers or 404-537-3406 for international callers and entering the conference ID # 7351587.

On March 5, 2020 Corvus Pharmaceuticals, Inc. (Nasdaq: CRVS), a clinical-stage biopharmaceutical company focused on the development and commercialization of precisely targeted oncology therapies and the utilization of novel biomarkers to enhance patient selection, provided a business update and reported financial results for the fourth quarter and year ended December 31, 2019 (Press release, Corvus Pharmaceuticals, MAR 5, 2020, View Source [SID1234555220]).

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"In 2019, we continued to efficiently advance our pipeline and exited the year with three candidates in clinical trials," said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. "We have presented updated data for each of these programs at major medical meetings and our academic collaborators are beginning to publish data from our studies in peer-reviewed journals, including a key publication for ciforadenant, our most advanced product, in Cancer Discovery in January. This article presented results demonstrating responses in patients with advanced refractory renal cell cancer and also reported on the identification of the Adenosine Gene Signature, a novel predictive biomarker."

"We presented data from our ongoing Phase 1/1b clinical trial with ciforadenant in prostate cancer at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancer Symposium (ASCO GU) meeting in February 2020 and on CPI-818 at the T-Cell Lymphoma Forum in January 2020. We look forward to reporting more mature data from these trials during the year."

Recent Achievements

CPI-444: A2A Receptor Antagonist of Adenosine

Publication of peer-reviewed study in Cancer Discovery covering results in 68 patients with advanced refractory renal cell cancer (RCC) treated with ciforadenant monotherapy and in combination with Genentech’s Tecentriq (atezolizumab), an anti-PD-L1 antibody. The publication describes the discovery of the Adenosine Gene Signature, which was shown in the study to identify patients most likely to respond to treatment with ciforadenant. In the study, for patients with available tumor biopsies, Adenosine Gene Signature positive patients had a 17% overall response rate by RECIST criteria vs 0% in Adenosine Gene Signature negative patients.
Enrolled additional patients (25 to date) with advanced refractory RCC in an amended Phase 1b/2 clinical trial evaluating ciforadenant in combination with Tecentriq intended to further evaluate the findings of the 68 patient study published in Cancer Discovery. To date, the results appear consistent with earlier results that Adenosine Gene Signature positive patients are more likely to respond to ciforadenant.
Presentation of safety and preliminary efficacy data in 35 patients with advanced refractory metastatic castrate resistant prostate cancer (mCRPC) treated with ciforadenant monotherapy and in combination with Tecentriq at the ASCO (Free ASCO Whitepaper) GU Cancer Symposium in February 2020. The preliminary data indicated that ciforadenant is active in mCRPC, and that the Adenosine Gene Signature correlated with CD73 expression in tumor biopsies.
CPI-006: Anti-CD73 Antibody

Oral presentation summarizing the safety and immunologic effects of CPI-006 in a phase 1/1b clinical trial at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) in November 2019. The presentation reported the in vivo effects of CPI-006 on B-cell activation, function and migration, supporting a new immuno-oncology approach with CPI-006 via activation of immune cells and the inhibition of adenosine production.
The trial will enroll up to 350 patients with advanced cancer evaluating CPI-006 as a single agent and in combination with ciforadenant or pembrolizumab.
Selected recommended dose of 18 mg/kg, or a fixed dose of 1200 mg, and initiated the disease expansion phase in the monotherapy and in combination with ciforadenant arms of the study. CPI-006 was well tolerated at all levels, with no dose limiting toxicities (doses ranged from 1 to 18 mg/kg).
Initiated enrollment in the combination cohort of CPI-006 and pembrolizumab.
Preliminary anti-tumor activity has been seen in mCRPC and renal cell cancer using monotherapy and in combination with ciforadenant.
CPI-818: A small molecule ITK inhibitor

Presentation of safety, pharmacokinetics and immunologic effects of CPI-818 in patients with refractory T-cell lymphomas in a poster at the American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting in December 2019 and in an oral session at the T-Cell Lymphoma Forum in January. These studies demonstrated that CPI-818 blocked proliferation of lymphoma cells in vitro.
The presentation at the T-Cell Forum reported on Phase 1 data in 16 patients. No dose limiting toxicities were observed at doses up to 600 mg oral, twice per day. Two patients with cutaneous T-cell lymphoma (CTCL) have shown improvement and 11 patients remained on the study as of the data cut-off date of January 2020.
Receptor occupancy studies indicate that complete occupancy may occur with doses of 600 mg twice per day.
Financial Results
As of December 31, 2019, Corvus had cash, cash equivalents and marketable securities totaling $78.0 million. This amount compared to cash, cash equivalents and marketable securities of $114.6 million at December 31, 2018. Corvus expects full year 2020 net cash used in operating activities to be between $39 million and $42 million.

Research and development expenses for the three months and full year ended December 31, 2019 totaled $8.9 million and $38.0 million, respectively, compared to $8.4 million and $38.6 million for the same periods in 2018. In the fourth quarter of 2019, the increase of $0.5 million was primarily due to an increase in outside CPI-006 and CPI-818 costs, partially offset by a decrease in outside ciforadenant costs. For the full year 2019, the decrease of $0.6 million was primarily due to a decrease in outside ciforadenant costs, partially offset by an increase in outside CPI-006 and CPI-818 costs and an increase in personnel costs.

The net loss for the three months and year ended December 31, 2019 was $11.0 million and $46.7 million, respectively, compared to $10.5 million and $46.9 million for the same periods in 2018. Total stock compensation expense for the three months and year ended December 31, 2019 was $1.7 million and $7.3 million, respectively, compared to $1.8 million and $7.1 million for the same periods in 2018.

Conference Call Details
Corvus will host a conference call and webcast today, Thursday, March 5, 2020, at 4:30 p.m. ET (1:30 p.m. PT), during which time management will provide a business update and discuss the fourth quarter 2019 financial results. The conference call can be accessed by dialing 1-800-263-0877 (toll-free domestic) or 1-720-543-0197 (international) and using the conference ID 3380789. The live webcast may be accessed via the investor relations section of the Corvus website. A replay of the webcast will be available on Corvus’ website for 90 days following the call.

On March 5, 2020 Syros Pharmaceuticals (NASDAQ:SYRS), a leader in the development of medicines that control the expression of genes, reported financial results for the quarter ended December 31, 2019, and provided an update on recent accomplishments and upcoming events (Press release, Syros Pharmaceuticals, MAR 5, 2020, View Source [SID1234555236]).

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"We are entering 2020 in a position of strength," said Nancy Simonian, M.D., Chief Executive Officer of Syros. "Following the recent initiation of our Phase 1 trial of SY-5609, we are advancing two oral investigational medicines through development in multiple cancer patient populations that we believe are most likely to respond to these targeted agents, both with meaningful data readouts expected in the fourth quarter. Meanwhile, our gene control platform continues to fuel a robust preclinical and discovery pipeline in oncology and monogenic diseases. We are committed to executing with excellence on our ongoing efforts and, longer term, to leveraging our deep understanding of the regulatory genome to deliver much-needed medicines that provide profound benefits for patients."

Upcoming Milestones:

SY-1425

Report potential proof-of-concept data in the fourth quarter of 2020 from ongoing Phase 2 trial cohort evaluating SY-1425 in combination with azacitidine in RARA-positive relapsed or refractory acute myeloid leukemia (AML) patients.
Report mature data in the fourth quarter of 2020 from fully enrolled Phase 2 trial cohorts evaluating SY-1425 in combination with azacitidine in newly diagnosed AML patients who are not suitable candidates for standard chemotherapy.
SY-5609

Report initial safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) data in fourth quarter of 2020 from dose-escalation portion of Phase 1 trial evaluating SY-5609 in patients with breast, colorectal, lung and ovarian cancers, as well as in patients with solid tumors of any histology that harbor Rb pathway alterations.
Report additional dose-escalation data, including clinical activity data, in mid-2021.
Preclinical Pipeline

Nominate next development candidate by the end of 2021.
Recent Pipeline Highlights:

In January 2020, Syros presented preclinical data showing that inhibiting cyclin-dependent kinase (CDK) 7 and CDK12 result in different transcriptional effects at the 2020 Keystone Symposia Cancer Epigenetics: New Mechanisms and Therapeutic Opportunities. The data showed that CDK12 inhibition preferentially decreases expression of genes with longer transcripts, a phenomenon not observed with CDK7 inhibition, pointing to distinct therapeutic opportunities for these two novel approaches to benefit patients with difficult-to-treat cancers. Also at Keystone, Syros presented on two new methods for identifying genes and transcriptional targets upon which specific cancers are particularly dependent for their survival.
In January 2020, Syros dosed the first patient in its Phase 1 clinical trial of SY-5609. The multi-center, open-label, dose-escalation trial is expected to enroll approximately 60 patients with breast, colorectal, lung or ovarian cancer, or with solid tumors of any histology that harbor Rb pathway alterations. The primary objectives of the trial are to assess the safety and tolerability of escalating doses of SY-5609, with the goal of establishing a maximum tolerated dose. Additional objectives include assessments of anti-tumor activity, PK, PD and predictive biomarkers of response. In a future expansion portion of the trial, multiple cohorts are planned to further evaluate the safety and anti-tumor activity of SY-5609 as both a single agent and in combination with other therapies.
In December 2019, Syros presented preclinical data demonstrating its discovery and validation of a novel fetal hemoglobin repressor, Nuclear Factor I X (NFIX) at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. Data showed that, when knocked down in primary cells and an erythroid cell line expressing adult hemoglobin, NFIX induced fetal hemoglobin in nearly 100% of cells and increased total fetal hemoglobin levels to 40%, exceeding levels that are associated with a functional cure in a subset of sickle cell disease (SCD) patients.
In November 2019, Syros and its collaborators from the Whitehead Institute for Biomedical Research presented on the identification of core drivers of metastasis in triple-negative breast cancer at the 2019 San Antonio Breast Cancer Symposium.
Recent Corporate Highlights:

In February 2020, Syros announced the closing of a $60 million senior secured loan facility with Oxford Finance, LLC. Under the terms of the financing, $20 million was drawn down at closing, and $40 million will be available across two tranches, subject to certain conditions and achievement of milestones.
In December 2019, Syros appointed Mark Alles, the former Chairman and Chief Executive Officer of Celgene Corporation, to its Board of Directors. Mr. Alles is a recognized biopharmaceutical executive with a proven record of building successful global oncology organizations and commercializing innovative therapies.
In December 2019, Syros entered into a collaboration with Global Blood Therapeutics (GBT) to discover, develop and commercialize novel oral medicines for SCD and beta thalassemia. Under the agreement, Syros will use its gene control platform to identify therapeutic targets and discover drugs that induce fetal hemoglobin, and GBT will receive an option to obtain an exclusive worldwide license to develop, manufacture and commercialize products resulting from the collaboration. Under the terms of the agreement, Syros received a $20 million upfront payment. GBT is also obligated to fund up to approximately $40 million in research expenses for at least three years. Should GBT exercise its option under the agreement, Syros could receive up to $315 million in option exercise, development, regulatory, commercialization and sales-based milestones per product candidate and product resulting from the collaboration, in addition to mid- to high-single digit royalties on sales of products resulting from the collaboration.
Fourth Quarter 2019 Financial Results:

Cash, cash equivalents and marketable securities as of December 31, 2019 were $91.4 million, compared with $99.7 million on December 31, 2018. This reflects aggregate net proceeds of approximately $65 million from Syros’ two concurrent underwritten public offerings, which closed in April 2019 but does not include the $20 million upfront payment received in connection with entry into collaboration with GBT or the $20 million from the initial tranche of the Oxford loan facility.

For the fourth quarter of 2019, Syros reported a net loss of $19.7 million, or $0.46 per share, compared to a net loss of $18.0 million, or $0.54 per share, for the same period in 2018.

Revenues were $0.5 million for the fourth quarter of 2019, as compared to $0.9 million for the fourth quarter of 2018. Revenues in both the fourth quarter of 2019 and the fourth quarter of 2018 were earned under Syros’ collaboration with Incyte Corporation.
Research and development (R&D) expenses were $14.3 million for the fourth quarter of 2019, as compared to $15.1 million for the same period in 2018. This decrease was primarily attributable to the portfolio prioritization decision made during the quarter to discontinue the SY-1365 program.
General and administrative (G&A) expenses were $6.4 million for the fourth quarter of 2019, as compared to $4.4 million for the same period in 2018. This increase was primarily attributable to an increase in employee related expenses due to increased headcount, as well as stock-based compensation expense related to the accelerated vesting of certain performance-based stock options following the execution of the Global Blood Therapeutics collaboration in December 2019.
Full Year 2019 Financial Results:

For the full year ended December 31, 2019, Syros reported a net loss of $75.4 million, or $1.88 per share, compared to a net loss of $62.3 million, or $1.91 per share, for the same period in 2018.

Revenues were $2.0 million for the year ended December 31, 2019, as compared to $2.1 million for the same period in 2018. Revenues in both 2019 and 2018 related entirely to the Incyte collaboration.
R&D expenses were $58.2 million for the year ended December 31, 2019, as compared to $50.2 million for the same period in 2018. This increase was primarily attributable to the continued advancement of the Company’s existing clinical trials and advancement of its preclinical programs, including completing SY-5609 IND-enabling studies.
G&A expenses were $21.5 million for the year ended December 31, 2019, as compared to $16.2 million for the same period in 2018. This increase was primarily attributable to an increase in employee related expenses due to increased headcount.
Financial Guidance:

Based on its current plans, Syros believes that its existing cash, cash equivalents and marketable securities, including the upfront payment received in connection with the GBT collaboration and the initial tranche of the Oxford loan facility, will be sufficient to fund its planned operating expenses and capital expenditures requirements into 2022, beyond key milestones expected for both SY-1425 and SY-5609.

Conference Call and Webcast:

Syros will host a conference call today at 8:30 a.m. ET to discuss these fourth quarter and full year 2019 financial results and provide a corporate update.

To access the live conference call, please dial (866) 595-4538 (domestic) or (636) 812-6496 (international) and refer to conference ID 2764269. A webcast of the call will also be available on the Investors & Media section of the Syros website at www.syros.com. An archived replay of the webcast will be available for approximately 30 days following the call.

On March 5, 2020 Arbutus Biopharma Corporation (Nasdaq: ABUS), a Hepatitis B Virus (HBV) therapeutic solutions company, reported its fourth quarter and year end 2019 financial results, confirms 2020 corporate objectives and provides pipeline update (Press release, Arbutus Biopharma, MAR 5, 2020, View Source [SID1234555197]).

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"Arbutus is focused on developing a portfolio of medicines with different mechanisms of action that we believe could provide a functional cure for people with chronic hepatitis B," said William Collier, Arbutus’ President and Chief Executive Officer. "Our key objectives for 2020 are to complete and report results from the Phase 1a/b clinical trial of AB-729, our proprietary subcutaneous RNAi agent, and rapidly advance our next-generation oral capsid inhibitor, AB-836, through IND-enabling studies by year end.

Mr. Collier added, "We remain on track to announce preliminary safety and efficacy results from multiple single-dose cohorts in the Phase 1a/1b clinical trial for AB-729 later this month."

Pipeline Update

AB-729

AB-729 is an RNA interference (RNAi) therapeutic targeted to hepatocytes using Arbutus’ novel covalently conjugated N-acetylgalactosamine (GalNAc) delivery technology that enables subcutaneous delivery. AB-729 inhibits viral replication and reduces all HBV antigens, including hepatitis B surface antigen (HBsAg), in preclinical models. Reducing HBsAg is thought to be a key prerequisite to enable reawakening of a patient’s immune system to respond to the virus.

Arbutus is currently conducting a single- and multiple-dose Phase 1a/1b clinical trial for AB-729 to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of AB-729 in healthy volunteers and in subjects with chronic hepatitis B (CHB) infection.

Preliminary safety data in single-dose cohorts of healthy subjects and safety and efficacy data in single-dose cohorts of subjects with CHB infection are expected later this month. Additional single-dose data and preliminary multi-dose data are expected in the second half of 2020.

AB-836

AB-836 is an oral HBV capsid inhibitor. HBV core protein assembles into a capsid structure, which is required for viral replication. The current standard-of-care therapy for HBV, primarily nucleoside analogues that work by inhibiting the viral polymerase, significantly reduce virus replication, but not completely. Capsid inhibitors inhibit replication by preventing the assembly of functional viral capsids. They also have been shown to inhibit the uncoating step of the viral life cycle thus reducing the formation of new covalently closed circular DNA (cccDNA), the viral reservoir which resides in the cell nucleus.

In January 2020, Arbutus selected AB-836 as its next-generation oral capsid inhibitor. AB-836 is a novel chemical series differentiated from Arbutus’ previously discontinued capsid inhibitor candidate, AB-506, and other competitor compounds in the capsid inhibitor space. AB-836 has the potential for increased potency and an enhanced resistance profile compared to AB-506, our previous generation capsid inhibitor that was discontinued in October 2019. Arbutus anticipates completing IND-enabling studies by the end of 2020.

Early R&D Programs

Arbutus continues a focused discovery effort on follow-on compounds for its current HBV pipeline, including the development of oral RNA-destabilizers that have shown compelling anti-viral effects in multiple HBV preclinical models. Arbutus is now focused on advancing a next-generation oral HBV specific RNA-destabilizer with chemical scaffolds distinct from AB-452 through lead optimization. Arbutus also has compounds in lead optimization that are potentially capable of reawakening patients’ HBV-specific immune response by inhibiting PD-L1.

Cash Position and 2020 Cash Guidance

Arbutus ended the year with $90.8 million in cash, cash equivalents and short-term investments which the Company believes is sufficient to fund operations into mid-2021. Arbutus expects to utilize between $54 to $58 million of cash and investments to fund operations in 2020.

Financial Results

Cash, Cash Equivalents and Investments

Arbutus had cash, cash equivalents and short-term investments totaling $90.8 million as of December 31, 2019, as compared to $124.6 million as of December 31, 2018. The decreased cash balance was due primarily to the $71.0 million used in operating activities during the year ended December 31, 2019, partially offset by $18.5 million in net proceeds from the sale of Arbutus’ portion of a royalty entitlement on net sales of Alnylam Pharmaceuticals, Inc.’s ONPATTROTM (Partisiran) in the third quarter of 2019 and $18.6 million of net proceeds from the issuance of shares under Arbutus’ ATM program. Included in the $71.0 million used in operating activities is a $5.9 million payment in the third quarter of 2019 for an award rendered in an arbitration proceeding with the University of British Columbia. Subsequent to year end, Arbutus has received an additional $12.3 million of net proceeds from the issuance of shares under Arbutus’ ATM program during the first quarter of 2020 through March 4, 2020.

Net Loss

Net loss attributable to common shares for the year ended December 31, 2019, including non-cash charges of $43.8 million related to the impairment of an in-process research and development ("IPR&D") intangible asset and $22.5 million for the impairment of goodwill described further below, was $164.9 million ($2.89 basic and diluted loss per common share) as compared to $67.2 million ($1.21 basic and diluted loss per common share) in 2018. Net loss attributable to common shares also included non-cash expense for the accrual of coupon on the Company’s convertible preferred shares of $11.1 million in 2019 and $10.1 million in 2018, as well as non-cash equity losses associated with our investment in Genevant Sciences Ltd.’s ("Genevant") of $22.5 million in 2019 and non-cash equity gains of $19.3 million in 2018. Genevant is a company launched with Roivant Sciences Ltd., Arbutus largest shareholder, in April 2018.

ONPATTRO Royalty Entitlement

Arbutus has a royalty entitlement on global net sales of ONPATTRO (Patisiran) for the lipid nanoparticle delivery (LNP) technology licensed by Arbutus to Alnylam for this product. ONPATTRO is an RNAi therapeutic for the treatment of hereditary ATTR (hATTR) amyloidosis that has been approved by the U.S. Food and Drug Administration and the European Medicines Agency. In July 2019, Arbutus sold this royalty entitlement to OCM IP Healthcare Portfolio LP, an affiliate of the Ontario Municipal Employees Retirement System (collectively, OMERS), effective as of January 1, 2019, for $20 million in gross proceeds before advisory fees. OMERS will retain this royalty entitlement until it has received $30 million in royalties, at which point 100% of this royalty entitlement will revert to Arbutus. OMERS has assumed the risk of collecting up to $30 million of future royalty payments from Alnylam and Arbutus is not obligated to reimburse OMERS if they fail to collect any such future royalties. Arbutus recognized the $20 million of gross proceeds from this transaction as a liability, net of transaction costs. The Company is amortizing the liability to non-cash interest expense and will continue to recognize the royalty revenue that Alnylam pays to OMERS as non-cash royalty revenue.

In addition to the royalty entitlement from the Alnylam LNP license agreement, Arbutus is also receiving a second, lower royalty entitlement on global net sales of ONPATTRO originating from a settlement agreement and subsequent license agreement with Acuitas Therapeutics. The royalty entitlement from Acuitas has been retained by Arbutus and is not part of the royalty entitlement sale to OMERS.

Operating Expenses

Research and development expenses were $57.6 million for the year ended December 31, 2019 compared to $57.9 million in 2018. Research and development expenses for the year ended December 31, 2019 included costs associated with the Company’s Phase 1a/1b clinical trial for its RNAi agent (AB-729), Phase 1a/1b clinical trial for its oral capsid inhibitor (AB-506), which was discontinued in October 2019, and toxicology studies for its HBV RNA Destabilizer (AB-452), which was discontinued in February 2020. General and administrative expenses were $17.7 million in 2019 compared to $16.0 million in 2018. The increase in general and administrative expenses was due primarily to severance related to our former President and Chief Executive Officer’s departure from the Company in June 2019, partially offset by a decrease in professional fees. In accordance with the terms of his legacy employment agreement, our former President and Chief Executive Officer received $2.3 million in cash severance and the Company recognized $1.1 million of non-cash stock-based compensation expense for accelerated vesting of his stock options.

Additionally, the Company recorded a charge of $6.3 million in 2019 related to an arbitration award from the Company’s arbitration with the University of British Columbia.

Impairment of IPR&D Intangible Assets and Goodwill

The Company has historically carried IPR&D and goodwill from its acquisition of technologies and business combination as assets. All acquired IPR&D intangible assets relate to the Company’s cccDNA program. During the year ended December 31, 2019, the Company recorded a $43.8 million non-cash impairment expense to reduce the carrying value of its IPR&D intangible assets to zero. The Company also recognized a corresponding income tax benefit of $12.7 million related to the decrease in its deferred tax liability associated with the IPR&D intangible assets. The impairment was due to an indefinite delay in further development of the Company’s cccDNA program while the Company focuses on its other development programs.

Goodwill represents the excess of purchase price over the value assigned to the net tangible and identifiable intangible assets in connection with the business combination that formed Arbutus. The Company assessed changes in circumstances to determine if it was more likely than not that the fair value of the Company was below its carrying amount. Due to a sustained decrease in the Company’s share price during the year, the Company’s market capitalization was reduced below the book value of its net assets and the Company concluded that its fair value was below its carrying amount by an amount in excess of the carrying value of the goodwill. As a result, during the third quarter of 2019,

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the Company recorded a $22.5 million non-cash impairment expense to reduce the carrying value of its goodwill asset to zero.

Outstanding Shares

The Company had 64,780,314 common shares issued and outstanding as of December 31, 2019. In addition, the Company had approximately 8.6 million stock options outstanding and 1.164 million convertible preferred shares outstanding, which (including the annual 8.75% coupon) will be mandatorily convertible into approximately 23 million common shares on October 18, 2021.

Conference Call Today

Arbutus will hold a conference call and webcast today, Thursday, March 5, 2020 at 8:45 AM Eastern Time to provide a corporate update. You can access a live webcast of the call through the Investors section of Arbutus’ website at www.arbutusbio.com. Alternatively, you can dial (866) 393-1607 or (914) 495-8556 and reference conference ID 5084457.

An archived webcast will be available on the Arbutus website after the event. Alternatively, you may access a replay of the conference call by calling (855) 859-2056 or (404) 537-3406, and reference conference ID 5084457.

On March 5, 2020 Caladrius Biosciences, Inc. (Nasdaq: CLBS) ("Caladrius" or the "Company"), a clinical-stage biopharmaceutical company dedicated to the development of cellular therapies designed to reverse, not manage, cardiovascular disease, reported financial results for the three and twelve months ended December 31, 2019 (Press release, Caladrius Biosciences, MAR 5, 2020, View Source [SID1234555221]).

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"I am pleased with the Company’s many achievements throughout 2019 as we made significant progress advancing our CD34+ technology-based clinical programs while maintaining strict financial controls," stated David J. Mazzo, Ph.D., President and Chief Executive Officer of Caladrius. "Notably, in November at the American Heart Association Scientific Sessions 2019, we reported the data for those patients (17 of 20) who, at that time, had completed their six-month follow-up visit in our ESCaPE-CMD study of CLBS16. The results showed highly statistically significant improvement in coronary flow reserve ("CFR") correlating with angina symptom relief for patients with coronary microvascular dysfunction ("CMD") after a single administration of CLBS16. To our knowledge, this is the first therapy to show the ability to durably increase CFR and potentially reverse CMD after a single administration. We look forward to reporting the full study data in the first half of 2020 in an appropriate forum. In Japan, enrollment continues to progress for the study of CLBS12 in critical limb ischemia ("CLI"), and we anticipate completing enrollment in the first half of 2020. Current data in both the no-option CLI and Buerger’s Disease cohorts of that study (the latter cohort has been fully enrolled and data are available in our corporate presentation) remain corroborative of previously published results, which we believe are an indication of a high probability of clinical success of the trial. We continue to anticipate top line data for the full study in early 2021 leading to an earliest possible approval in Japan in late 2021 or early 2022. Finally, we have completed all preparatory measures for the initiation of the single confirmatory phase 3 study agreed with U.S. Food and Drug Administration (the "FDA") to conclude development of CLBS14 in no-option refractory disabling angina (NORDA) and are awaiting finalization of a funding plan before commencing the trial.

"We are excited about what lies ahead in 2020 and expect to build on this momentum as we continue to advance our clinical development pipeline and strive to achieve a number of important development milestones throughout the balance of the year," concluded Dr. Mazzo.

Fourth Quarter and Full Year 2019 Financial Highlights

Research and development expenses for the fourth quarter of 2019 were $2.8 million, an 84% increase compared with $1.5 million for the fourth quarter of 2018, and $10.8 million for 2019, a 42% increase compared with $7.6 million for 2018. Research and development in both the current year and prior year periods focused on the advancement of our ischemic repair platform and related to:

ongoing registration-eligible study expenses for CLBS12 in critical limb ischemia in Japan, whereby we continue to focus spending on our patient enrollment;

ongoing Phase 2 proof-of-concept study expenses for CLBS16 in coronary microvascular dysfunction, for which study enrollment was completed in the second quarter of 2019; and

expenses associated with preparation of our confirmatory Phase 3 study of CLBS14 in NORDA. In late 2019, we projected that the Phase 3 study would cost approximately $70 million in external expenses over the next several years to complete, and as a result, we elected to postpone the initiation of the study until we have confidence that we can access sufficient capital to allow us to complete the study uninterrupted

General and administrative expenses, which focus on general corporate related activities, were approximately $2.3 million for both the fourth quarters of 2019 and 2018, and $9.3 million for 2019, a slight decline compared to $9.4 million in 2018.

The net loss for the fourth quarter of 2019 was $5.0 million, or $0.47 per share, compared with $3.6 million, or $0.36 per share, for the fourth quarter of 2018. The net loss for 2019 was $19.4 million, or $1.88 per share, compared with $16.2 million, or $1.67 per share, for 2018.

Balance Sheet Highlights

As of December 31, 2019, Caladrius had cash, cash equivalents and marketable securities of $25.2 million. Based on existing programs and projections, the Company remains confident that its cash balances will fund its operations through at least the second quarter of 2021.

Conference Call

Caladrius’ management will host a conference call for the investment community later today, March 5, 2020, at 4:30 p.m. (ET) to discuss the financial results, provide a company update and answer questions.

Shareholders and other interested parties may participate on the conference call by dialing (866) 595-8403 (U.S.) or (706) 758-9979 (International), using the conference ID code: 4155934. The live webcast will be accessible via the Events page listed under the Investor section of the Company’s website at www.caladrius.com/investors/news-events/events.

For those unable to participate on the live conference call, an audio replay will be available approximately two hours after the conclusion of the call until 11:59 p.m. ET on March 12, 2020. To access the replay, please dial (855) 859-2056 (U.S.) or (404) 537-3406 (International) and provide the conference ID code: 4155934.

A webcast replay of the conference call will remain available on the Company’s website for 90 days.