On May 5, 2021 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for patients with cancer, reported business highlights and financial results for the first quarter ended March 31, 2021 (Press release, Fate Therapeutics, MAY 5, 2021, View Source [SID1234579182]).

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"During the first quarter of 2021, we strengthened our balance sheet by raising $460 million and successfully positioned our off-the-shelf, iPSC-derived NK cell pipeline to achieve significant clinical milestones across our disease franchises throughout the remainder of the year. We look forward to sharing Phase 1 clinical data from our FT516 and FT538 programs in relapsed / refractory AML at an investor event to be held alongside the ASGCT (Free ASGCT Whitepaper) conference. We are also pleased with the clinical expansion of our FT538 program into solid tumors, where we plan to combine with FDA-approved monoclonal antibodies targeting EGFR, HER2, and PDL1," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "While we are disappointed that the PROTECT study of ProTmune did not meet its primary endpoint for prevention of acute graft-versus-host disease following allogeneic stem cell transplant, we will now turn our full attention and resources to our deep pipeline of off-the-shelf, iPSC-derived cancer immunotherapies. We would like to sincerely thank the patients, caregivers and investigators who participated in the clinical investigation of ProTmune, and we intend to share our clinical findings with that community."

AML Disease Franchise

Interim Phase 1 Clinical Data for FT516 and FT538 Programs to be Featured at Upcoming Investor Event. On May 13, the Company plans to host a virtual investor event to highlight interim Phase 1 clinical data from its FT516 (hnCD16 engineered iPSC-derived NK cell) and FT538 (hnCD16 + IL-15RF + CD38KO engineered iPSC-derived NK cell) programs for the treatment of relapsed / refractory acute myeloid leukemia (AML). The Phase 1 study of FT516 as a monotherapy (NCT04023071) has enrolled the first and second dose cohorts (90 million and 300 million cells per dose, respectively), and dose escalation is ongoing with enrollment in the third dose cohort (900 million cells per dose). The Phase 1 study of FT538 as a monotherapy (NCT04614636) is enrolling in the first dose cohort (100 million cells per dose). The Company is also working with investigators from the Masonic Cancer Center, University of Minnesota to initiate a Phase 1 clinical trial of FT538 in combination with the CD38-targeted monoclonal antibody daratumumab in patients with relapsed / refractory AML, a therapeutic strategy designed to exploit the product candidate’s proprietary high-affinity, non-cleavable (hnCD16) receptor and CD38 knock-out (CD38KO) to target and eliminate CD38+ leukemic blasts.
ASGCT Symposium to Highlight Adaptive NK Cell Features and Functionality of FT538. At the 24th Annual American Society of Gene & Cell Therapy Meeting (ASGCT) (Free ASGCT Whitepaper) to be held virtually from May 11-14, Dr. Jeffrey S. Miller, Professor of Medicine, University of Minnesota and Deputy Director of the Masonic Cancer Center, plans to present preclinical data demonstrating that the metabolic, transcriptional and functional properties of FT538 are substantially similar to those of adaptive NK cells, a discrete subset of memory-like NK cells with superior effector function. First described as a well-defined subset of NK cells that expand in cytomegalovirus (CMV) seropositive individuals (Gumá et al., 2004), adaptive NK cells exhibit increased effector function, enhanced persistence, resistance to oxidative stress, and potent serial cytotoxicity. Dr. Miller’s presentation is scheduled to be held on May 11 during a session entitled Recent Advances and Future Directions of Gene and Cellular Therapies in Immune Oncology.
B-cell Malignancy Disease Franchise

New FT516 Phase 1 Clinical Data for B-cell Lymphoma to be Presented at ASCO (Free ASCO Whitepaper). Dose escalation is ongoing with enrollment in the fourth dose cohort (900 million cells per dose) in the Phase 1 clinical trial to assess the safety and determine the maximum dose of FT516 in combination with CD20-targeted monoclonal antibody therapies for the treatment of relapsed / refractory B-cell lymphoma (BCL) (NCT04023071). The Company plans to present new clinical data from the Phase 1 study as part of a poster session at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (ASCO) (Free ASCO Whitepaper) being held virtually from June 4-8. In December 2020, the Company reported positive interim data from the second and third dose cohorts (90 million and 300 million cells per dose, respectively), with three of four patients achieving an objective response including two complete responses.
Submitted FT596 Protocol Amendment to FDA to Assess Multi-dose Treatment Schedule. The Phase 1 clinical trial of FT596 (CAR19 + hnCD16 + IL-15RF engineered iPSC-derived NK cell) is designed to assess the safety and determine the maximum dose of FT596 as a monotherapy and in combination with CD20-targeted monoclonal antibody therapies for the treatment of relapsed / refractory BCL and chronic lymphocytic leukemia (CLL) (NCT04245722). Dose escalation of the single-dose treatment schedule is ongoing with enrollment in the third dose cohort (300 million cells) as monotherapy and in combination with rituximab for the treatment of BCL, and in the first dose cohort (30 million cells) as a monotherapy for the treatment of CLL. The Company has submitted a protocol amendment to the U.S. Food and Drug Administration (FDA) to also assess administration of multi-dose treatment schedules for FT596.
FT819 Product Attributes to be Featured in Oral Presentation at ASGCT (Free ASGCT Whitepaper). The Company is preparing to initiate a multi-center Phase 1 clinical trial of FT819, the first-ever off-the-shelf, allogeneic CAR T-cell therapy derived from a clonal master iPSC line, for patients with BCL, CLL, or acute lymphoblastic leukemia (ALL). In an oral presentation at ASGCT (Free ASGCT Whitepaper), the Company plans to describe the generation of the clonal master engineered iPSC line for FT819 using its proprietary iPSC platform, and to present preclinical data of FT819 characterizing its phenotypic and functional profile, including its expression of memory, activation and exhaustion markers, and its anti-tumor activity in comparison to primary CAR T cells. FT819 is engineered with several first-of-kind features designed to improve the safety and efficacy of CAR T-cell therapy including a novel 1XX CAR signaling domain targeting CD19+ malignancies (1XX-CAR19) that extends T-cell effector function without eliciting exhaustion; integration of the CAR transgene directly into the T-cell receptor alpha constant (TRAC) locus, which promotes uniform CAR expression and enhances T-cell potency; and complete bi-allelic disruption of T-cell receptor expression to prevent graft-versus-host disease.
Multiple Myeloma Franchise

Phase 1 Study for FT538 in Combination with Daratumumab Set for Initiation. The Phase 1 clinical trial is designed to assess three once-weekly doses of FT538 in combination with the CD38-targeted monoclonal antibody, daratumumab, for patients with relapsed / refractory multiple myeloma (NCT04614636). The Company will initiate enrollment at 100 million cells per dose upon clearance of the first dose cohort in the study’s AML regimen assessing FT538 as monotherapy.
FT576 Preclinical Data Presented at AACR (Free AACR Whitepaper) Demonstrate Super Anti-tumor Activity. At the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021 (AACR) (Free AACR Whitepaper) in April, the Company presented preclinical data for FT576 (CAR-BCMA + hnCD16 + IL-15RF + CD38KO engineered iPSC-derived NK cells), demonstrating superior in vivo persistence and anti-tumor activity as compared to cytokine-expanded primary NK cells in a disseminated xenograft model of multiple myeloma. In addition, the Company observed that multi-antigen targeting of FT576 in combination with daratumumab exhibits greater in vivo efficacy compared to primary CAR T cells in combination with a gamma secretase inhibitor. FT576 is derived from a clonal master iPSC line engineered with four functional components designed to enable multi-antigen targeting of myeloma cells, augment antibody-dependent cellular cytotoxicity (ADCC), promote NK cell activation without exogenous cytokine support, enhance cell persistence and prevent anti-CD38 monoclonal antibody-induced fratricide. The Company is preparing to initiate a multi-center Phase 1 clinical trial to assess single-dose and multi-dose treatment regimens of FT576 as monotherapy and in combination with CD38-targeted monoclonal antibody therapy for the treatment of relapsed / refractory multiple myeloma.
Solid Tumor Franchise

IND Application Allowed by FDA for FT538 in Combination with Monoclonal Antibody Therapy for Solid Tumors. The Company plans to initiate a multi-center Phase 1 clinical trial to assess the safety and determine the maximum dose of FT538 in combination with monoclonal antibody therapy for the treatment of a broad array of solid tumors. The novel therapeutic strategy is designed to exploit the product candidate’s hnCD16 receptor to promote ADCC, a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. The clinical protocol includes combination with three monoclonal antibodies: EGFR-targeted cetuximab; HER2-targeted trastuzumab; and PDL1-targeted avelumab. Each patient is eligible to receive up to two FT538 treatment cycles, with each cycle consisting of three days of outpatient lympho-conditioning, three once-weekly infusions of FT538, and monoclonal antibody therapy.
Preclinical Studies of FT536 CAR MICA/B Program Demonstrate Superiority over Primary NK Cells. At AACR (Free AACR Whitepaper), the Company highlighted its development of FT536, a novel CAR NK cell product candidate targeting the alpha-3 domain of the pan-tumor associated stress antigens MICA and MICB. In preclinical studies designed to increase the density of stress antigen expression and sensitivity of tumor cells to NKG2D-mediated recognition and killing by NK cells, FT536 demonstrated superior anti-tumor activity compared to cytokine-expanded primary NK cells across a broad array of cancer cell lines. The Company plans to submit an IND application in the second half of 2021 to initiate a Phase 1 clinical trial of FT536 for the treatment of solid tumors.
Novel B7H3-targeted Binding Domain Selected for Development of iPSC-derived CAR NK Cell Program. At AACR (Free AACR Whitepaper), the Company presented preclinical data demonstrating anti-tumor activity of its novel B7H3 binding domain, including when incorporated in a tri-specific NK cell engager (TriKE), a primary CAR T cell, and an iPSC-derived CAR NK cell. B7H3 is an immune checkpoint molecule of the B7 protein superfamily with broad expression in cancer and its upregulation is associated with metastatic cancer and poor prognosis. The Company is conducting preclinical development of multiplexed-engineered, iPSC-derived CAR B7H3 NK cell and T-cell product candidates for solid tumors.
ProTmune

Phase 2 PROTECT Study Did Not Meet Primary Endpoint for Prevention of Acute GvHD. The randomized, controlled and double-blinded PROTECT study was designed to assess the safety and efficacy of ProTmune, a patient-specific hematopoietic cell graft manufactured on-site at local transplant centers using the Company’s ex vivo small molecule modulation technology, for patients undergoing allogeneic stem cell transplant. The results failed to show a statistically-significant difference between ProTmune and control with respect to the primary endpoint of cumulative incidence of Grades 2-4 acute GvHD by Day 100, and the Company is discontinuing development of ProTmune.
Other Corporate Highlights

Completed $460 Million Public Offering. In January 2021, the Company completed an underwritten public offering of 5.1 million shares of its common stock priced at $85.50 per share and, in lieu of common stock to certain investors, pre-funded warrants to purchase 0.3 million shares of its common stock priced at $85.499 per pre-funded warrant.
First Quarter 2021 Financial Results

Cash & Investment Position: Cash, cash equivalents and investments as of March 31, 2021 were $888.4 million. This amount includes net proceeds to the Company of approximately $432 million from the January 2021 underwritten public offering.
Total Revenue: Revenue was $11.1 million for the first quarter of 2021, which was derived from the Company’s collaborations with Janssen and Ono Pharmaceutical.
R&D Expenses: Research and development expenses were $44.9 million for the first quarter of 2021, which includes $8.5 million of non-cash stock-based compensation expense.
G&A Expenses: General and administrative expenses were $12.5 million for the first quarter of 2021, which includes $4.5 million of non-cash stock-based compensation expense.
Shares Outstanding: Common shares outstanding were 93.9 million, and preferred shares outstanding were 2.8 million, as of March 31, 2021. Each preferred share is convertible into five common shares.
Today’s Conference Call and Webcast

The Company will conduct a conference call today, Wednesday, May 5, 2021 at 5:00 p.m. ET to review financial and operating results for the quarter ended March 31, 2021. In order to participate in the conference call, please dial 800-708-4539 (toll free) or 847-619-6396 (toll) and refer to conference ID 50156207. The live webcast can be accessed under "Events & Presentations" in the Investors section of the Company’s website at www.fatetherapeutics.com. The archived webcast will be available on the Company’s website beginning approximately two hours after the event.

On May 5, 2021 Supernus Pharmaceuticals, Inc. (Nasdaq: SUPN), a biopharmaceutical company focused on developing and commercializing products for the treatment of central nervous system (CNS) diseases, reported financial results for the first quarter of 2021, and associated Company developments (Press release, Supernus, MAY 5, 2021, View Source [SID1234579181]).

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"The approval of Qelbree provides pediatric patients living with ADHD a therapy with proven efficacy and a tolerable safety profile, and that is not a controlled substance," said Jack Khattar, President and CEO of Supernus Pharmaceuticals. "Our Qelbree commercial launch activities are ongoing and include engagement with both physicians and patient groups who have expressed great interest in this unique new alternative for the treatment of ADHD."

Net Product Sales

First quarter 2021 net product sales were $128.4 million, 39% higher than the same period in 2020.

Qelbree Launch Update

In April 2021, the U.S. Food and Drug Administration (FDA) approved Qelbree for the treatment of attention-deficit hyperactivity disorder (ADHD) in pediatric patients 6 to 17 years of age. The Company plans to make Qelbree available in the U.S. during the second quarter of 2021.
Supernus will conduct post-marketing commitment studies, including a new study of Qelbree in preschool aged children with ADHD, 4 to 5 years of age. The completion of these studies responds to a written request from the FDA and should therefore result in the FDA granting an additional 6 months of market exclusivity.
Product Pipeline Update

Qelbree (viloxazine, extended-release capsules) – Novel non-stimulant for the treatment of ADHD in adults

In December 2020, the Company announced positive results from a Phase III trial in adult patients with ADHD and plans to submit a supplemental New Drug Application (sNDA) to the FDA for Qelbree in adults in the third quarter of 2021.
SPN-830 (apomorphine infusion pump) – Continuous treatment of motor fluctuations ("on-off" episodes) in PD

The company recently met with the FDA to discuss the path forward for resubmission of the SPN-830 NDA. The FDA provided additional clarity related to the contents of the November 2020 Refusal to File (RTF) letter and the requirements for resubmission. The Company now plans to resubmit the SPN-830 NDA in the second half of 2021.
SPN-820 – Novel first-in-class activator of mTORC1

SPN-820 has advanced to a Phase II clinical program in treatment-resistant depression following the successful completion of a multiple-ascending dose (MAD) study in healthy volunteers. In the MAD study, SPN-820 exhibited a favorable safety and tolerability profile across a broad range of potentially therapeutic doses.
The Company expects to initiate a randomized Phase II clinical study in treatment-resistant depression by the end of 2021.
Financial Highlights

First quarter 2021 operating earnings were $13.2 million, as compared to $29.0 million in the first quarter 2020. In the first quarter of 2021, the Company recorded non-cash research and development expense of $15 million related to the equity investment in Navitor as a result of the accounting impact of the March 2021 Navitor corporate restructuring and non-cash contingent consideration expense of $1 million associated with the 2020 USWM acquisition. Operating earnings for the first quarter of 2021 included amortization of intangible assets expense of $6.0 million, compared to $1.3 million in the first quarter of 2020.

First quarter 2021 net earnings and diluted earnings per share were $5.7 million and $0.11, respectively, as compared to $21.5 million, or $0.40 per diluted share, in the same period last year.

As of March 31, 2021, the Company had $807.7 million in cash, cash equivalents and marketable securities, compared to $772.9 million as of December 31, 2020.

Full Year 2021 Financial Guidance

For full year 2021, the Company reiterates its prior financial guidance and added full year 2021 effective tax rate guidance as set forth below:

1) Total revenues includes net product sales and royalty revenue. Includes $10 million for Qelbree net product sales.
2) Combined research and development and selling, general and administrative expenses.
3) Operating earnings include amortization of intangible assets and contingent consideration expense.
4) The full year 2021 effective tax rate guidance of 28% – 31% is above the normally expected range of 26% – 28% due to the effect of discrete tax items in the period.

Conference Call Details

The Company will hold a conference call hosted by Jack Khattar, President and Chief Executive Officer and Jim Kelly, Executive Vice President and Chief Financial Officer, to discuss these results at 4:30 p.m. Eastern Time, today, May 5, 2021.

Please refer to the information below for conference call dial-in information and webcast registration. Callers should dial in approximately 10 minutes prior to the start of the call.

On May 5, 2021 Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) reported financial results for the first quarter ended March 31, 2021, including sales of TAVALISSE (fostamatinib disodium hexahydrate) tablets, for the treatment of adults with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment (Press release, Rigel, MAY 5, 2021, View Source [SID1234579180]).

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"We continued to make significant progress in achieving important corporate and clinical milestones in the first quarter, which is a true testament to the dedication of our team to bring meaningful treatment options to those patients who need them the most," said Raul Rodriguez, Rigel’s president and CEO. "Following our recent announcement of positive topline data from the Phase 2 trial of fostamatinib in hospitalized patients with COVID-19 and our partnership with Eli Lilly for our RIP1 inhibitor program, we are excited by the prospects that the rest of 2021 holds for Rigel."

Business Update
In April 2021, Rigel reported positive topline data from the multi-center, Phase 2 clinical trial evaluating the safety of fostamatinib, Rigel’s oral spleen tyrosine kinase (SYK) inhibitor, for the treatment of hospitalized patients with COVID-19. The trial met its primary endpoint of safety, and showed broad and consistent improvement in numerous efficacy endpoints including mortality, ordinal scale assessment, and number of days in the ICU. The trial was conducted in collaboration with the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health (NIH), and Inova Health System. The NHLBI is expected to publish a full analysis of the trial data in a peer-reviewed journal. Rigel is discussing these results with health authorities, including the U.S. Food and Drug Administration (FDA), and intends to apply for Emergency Use Authorization (EUA) for fostamatinib for the treatment of hospitalized COVID-19 patients.

Rigel’s Phase 3 clinical trial to further evaluate fostamatinib in hospitalized patients with COVID-19 is currently enrolling. Rigel was awarded $16.5 million from the U.S. Department of Defense’s (DOD) Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND) to support this Phase 3 clinical trial. The study is designed to evaluate fostamatinib for prevention of progression to severe disease in hospitalized patients with COVID-19 without respiratory failure that have certain high-risk prognostic factors. This multi-center, double-blind, placebo-controlled study will randomly assign patients to either fostamatinib plus standard of care (SOC) or matched placebo plus SOC (1:1). Treatment will be administered orally twice daily for 14 days. There will be a follow-up period to day 60. The primary endpoint of this study is the proportion of subjects who progress to severe/critical disease within 29 days. In addition, Rigel’s COVID-19 program includes an investigator-sponsored trial currently being conducted by Imperial College London.

Rigel’s FORWARD study, a Phase 3 pivotal trial of TAVALISSE in patients with warm autoimmune hemolytic anemia (wAIHA), has enrolled 72 of 90 patients as of May 5, 2021. If approved, TAVALISSE has the potential to be the first to market therapy for patients with wAIHA. The FDA has granted Fast Track designation as well as Orphan Drug designation to TAVALISSE for the treatment of wAIHA.

In the first quarter of 2021, 1,599 bottles of TAVALISSE were shipped to patients and clinics, an increase of 14% year over year. Net product sales for the first quarter decreased 2% year over year to $12.4 million. During the quarter, the company experienced typical first quarter reimbursement issues such as the resetting of co-pays and the Medicare donut hole, along with physician and patient access issues created by the COVID-19 pandemic. Incrementally, the company’s net product sales were negatively impacted by a significant 235 bottle decrease in bottles remaining in its distribution channels compared to Q4 2020.

In April 2021, Rigel received a $125 million upfront cash payment from its collaboration with Eli Lilly and Company (Lilly), following the expiration of the waiting period under the Hart-Scott Rodino Antitrust Improvements Act of 1976. In February 2021, Rigel and Lilly entered into a global exclusive license agreement and strategic collaboration to develop and commercialize Rigel’s R552, a receptor-interacting serine/threonine-protein kinase 1 (RIP1) inhibitor, for all indications including autoimmune and inflammatory diseases. Rigel and Lilly are currently focused on the planning for the initiation of a Phase 2 clinical trial. Pursuant to the collaboration, Lilly will also lead all clinical development of central nervous system (CNS) penetrating RIP1 inhibitors. Rigel is eligible to receive up to an additional $835 million in potential development, regulatory and commercial milestone payments, as well as tiered royalties that will vary depending upon Rigel’s clinical development investment.

Rigel is also advancing the development of its IRAK1/4 program, where it intends to pursue both hematology/oncology and rare immune disease opportunities. Rigel has begun discussions with the FDA regarding initiating a Phase 2 clinical trial in low-risk myelodysplastic syndrome (MDS) and is also in discussions regarding academic medical collaborations in this indication. In rare immune diseases, the company is exploring opportunities including palmoplantar pustulosis (PPP), hidradenitis suppurativa (HS), and others.

Rigel’s partner Kissei Pharmaceutical Co., Ltd. (Kissei) has completed enrollment of its Phase 3 clinical trial of fostamatinib in adult Japanese patients with chronic ITP. In October 2018, Rigel and Kissei entered into an exclusive agreement to develop and commercialize fostamatinib in all current and potential indications in Japan, China, Taiwan, and the Republic of Korea.

Financial Update
For the first quarter of 2021, Rigel reported net income of $39.5 million, or $0.23 per basic share and $0.22 per diluted share, compared to net income of $21.2 million, or $0.13 per basic and diluted share, for the same period of 2020.

In the first quarter of 2021, total revenues were $81.0 million, consisting of $12.4 million in TAVALISSE net product sales, $65.6 million in contract revenues from collaborations and $3.0 million in government contract revenue.

Contract revenues from collaborations of $65.6 million for the first quarter of 2021 consisted of $60.6 million in revenue related to Rigel’s license agreement with Lilly, $4.0 million in revenue related to the grant of non-exclusive license of a certain patent to an unrelated third-party company, and $1.0 million in revenue for the delivery of drug supply under its collaboration agreement with Grifols. Government contract revenue was related to the income that Rigel recognized pursuant to the agreement it entered into in January 2021 with the DOD to support Rigel’s ongoing Phase 3 clinical trial of fostamatinib in hospitalized patients with COVID-19.

Rigel reported total costs and expenses of $39.3 million in the first quarter of 2021, compared to $34.7 million for the same period in 2020. The increase in costs and expenses was primarily due to increases in personnel-related costs, stock-based compensation expense, and research and development costs related to its ongoing Phase 3 clinical trial in hospitalized patients with COVID-19 and development of its IRAK 1/4 inhibitor program, partially offset by the decrease in research and development costs due to the completion of a Phase 1 clinical trial for its RIP1 inhibitor program.

As of March 31, 2021, Rigel had cash, cash equivalents and short-term investments of $39.3 million, compared to $57.3 million as of December 31, 2020. Cash, cash equivalents and short-term investments as of March 31, 2021, does not include the $125.0 million upfront payment received from Lilly in April 2021.

Conference Call and Webcast with Slides Today at 4:30pm Eastern Time
Rigel will hold a live conference call and webcast today at 4:30pm Eastern Time (1:30pm Pacific Time).

Participants can access the live conference call by dialing (877) 407-3088 (domestic) or (201) 389-0927 (international). The conference call and accompanying slides will also be webcast live and can be accessed from the Investor Relations section of the company’s website at www.rigel.com. The webcast will be archived and available for replay after the call via the Rigel website.

About ITP
In patients with ITP (immune thrombocytopenia), the immune system attacks and destroys the body’s own blood platelets, which play an active role in blood clotting and healing. Common symptoms of ITP are excessive bruising and bleeding. People suffering with chronic ITP may live with an increased risk of severe bleeding events that can result in serious medical complications or even death. Current therapies for ITP include steroids, blood platelet production boosters (TPO-RAs) and splenectomy. However, not all patients respond to existing therapies. As a result, there remains a significant medical need for additional treatment options for patients with ITP.

About AIHA
Autoimmune hemolytic anemia (AIHA) is a rare, serious blood disorder in which the immune system produces antibodies that result in the destruction of the body’s own red blood cells. AIHA affects approximately 45,000 adult patients in the U.S. and can be a severe, debilitating disease. To date, there are no disease-targeted therapies approved for AIHA, despite the unmet medical need that exists for these patients. Warm antibody AIHA (wAIHA), the most common form of AIHA, is characterized by the presence of antibodies that react with the red blood cell surface at body temperature.

About COVID-19 & SYK Inhibition
COVID-19 is the infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). SARS-CoV-2 primarily infects the upper and lower respiratory tract and can lead to acute respiratory distress syndrome (ARDS). Additionally, some patients develop other organ dysfunction including myocardial injury, acute kidney injury, shock resulting in endothelial dysfunction and subsequently micro and macrovascular thrombosis.1 Much of the underlying pathology of SARS-CoV-2 is thought to be secondary to a hyperinflammatory immune response associated with increased risk of thrombosis.2

SYK is involved in the intracellular signaling pathways of many different immune cells. Therefore, SYK inhibition may improve outcomes in patients with COVID-19 via inhibition of key Fc gamma receptor (FcγR) and c-type lectin receptor (CLR) mediated drivers of pathology, such as inflammatory cytokine release by monocytes and macrophages, production of neutrophil extracellular traps (NETs) by neutrophils, and platelet aggregation.3,4,5 Furthermore, SYK inhibition in neutrophils and platelets may lead to decreased thromboinflammation, alleviating organ dysfunction in critically ill patients with COVID-19.

For more information on Rigel’s comprehensive clinical program in COVID-19, go to: View Source

About R552
The investigational candidate, R552, is an orally available, potent and selective inhibitor of receptor-interacting serine/threonine-protein kinase 1 (RIP1). RIP1 is believed to play a critical role in necroptosis. Necroptosis is a form of regulated cell death where the rupturing of cells leads to the dispersion of their inner contents, which induces immune responses and enhances inflammation. In preclinical studies, R552 prevented joint and skin inflammation in a RIP1-mediated murine model of inflammation and tissue damage. The safety and efficacy of R552 has not been established by the FDA or any healthcare authority.

About R835
The investigational candidate, R835, is an orally available, potent and selective inhibitor of IRAK1 and IRAK4 that has been shown preclinically to block inflammatory cytokine production in response to toll-like receptor (TLR) and the interleukin-1 receptor (IL-1R) family signaling. TLRs and IL-1Rs play a critical role in the innate immune response, and dysregulation of these pathways can lead to a variety of inflammatory pathological conditions. R835 treatment demonstrates amelioration of clinical symptoms in multiple rodent models of inflammatory disease including psoriasis, arthritis, lupus, multiple sclerosis and gout. The safety and efficacy of R835 has not been established by the FDA or any healthcare authority.

About TAVALISSE
Indication
TAVALISSE (fostamatinib disodium hexahydrate) tablets is indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.

Important Safety Information
Warnings and Precautions

Hypertension can occur with TAVALISSE treatment. Patients with pre-existing hypertension may be more susceptible to the hypertensive effects. Monitor blood pressure every 2 weeks until stable, then monthly, and adjust or initiate antihypertensive therapy for blood pressure control maintenance during therapy. If increased blood pressure persists, TAVALISSE interruption, reduction, or discontinuation may be required.
Elevated liver function tests (LFTs), mainly ALT and AST, can occur with TAVALISSE. Monitor LFTs monthly during treatment. If ALT or AST increase to >3 x upper limit of normal, manage hepatotoxicity using TAVALISSE interruption, reduction, or discontinuation.
Diarrhea occurred in 31% of patients and severe diarrhea occurred in 1% of patients treated with TAVALISSE. Monitor patients for the development of diarrhea and manage using supportive care measures early after the onset of symptoms. If diarrhea becomes severe (≥Grade 3), interrupt, reduce dose or discontinue TAVALISSE.
Neutropenia occurred in 6% of patients treated with TAVALISSE; febrile neutropenia occurred in 1% of patients. Monitor the ANC monthly and for infection during treatment. Manage toxicity with TAVALISSE interruption, reduction, or discontinuation.
TAVALISSE can cause fetal harm when administered to pregnant women. Advise pregnant women the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose. Verify pregnancy status prior to initiating TAVALISSE. It is unknown if TAVALISSE or its metabolite is present in human milk. Because of the potential for serious adverse reactions in a breastfed child, advise a lactating woman not to breastfeed during TAVALISSE treatment and for at least 1 month after the last dose.
Drug Interactions

Concomitant use of TAVALISSE with strong CYP3A4 inhibitors increases exposure to the major active metabolite of TAVALISSE (R406), which may increase the risk of adverse reactions. Monitor for toxicities that may require a reduction in TAVALISSE dose.
It is not recommended to use TAVALISSE with strong CYP3A4 inducers, as concomitant use reduces exposure to R406.
Concomitant use of TAVALISSE may increase concentrations of some CYP3A4 substrate drugs and may require a dose reduction of the CYP3A4 substrate drug.
Concomitant use of TAVALISSE may increase concentrations of BCRP substrate drugs (eg, rosuvastatin) and P-Glycoprotein (P-gp) substrate drugs (eg, digoxin), which may require a dose reduction of the BCRP and P-gp substrate drug.
Adverse Reactions

Serious adverse drug reactions in the ITP double-blind studies were febrile neutropenia, diarrhea, pneumonia, and hypertensive crisis, which occurred in 1% of TAVALISSE patients. In addition, severe adverse reactions occurred including dyspnea and hypertension (both 2%), neutropenia, arthralgia, chest pain, diarrhea, dizziness, nephrolithiasis, pain in extremity, toothache, syncope, and hypoxia (all 1%).
Common adverse reactions (≥5% and more common than placebo) from FIT-1 and FIT-2 included: diarrhea, hypertension, nausea, dizziness, ALT and AST increased, respiratory infection, rash, abdominal pain, fatigue, chest pain, and neutropenia.

On May 5, 2021 CorMedix Inc. (Nasdaq: CRMD), a biopharmaceutical company focused on developing and commercializing therapeutic products for the prevention and treatment of infectious and inflammatory disease, reported that it will report its financial results for the first quarter ended March 31, 2021, after the market close on Thursday, May 13, and will host a corporate update conference call at 4:30pm Eastern Time (Press release, CorMedix, MAY 5, 2021, View Source [SID1234579179]).

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On May 5, 2021 Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) reported its financial results for the first quarter of 2021 and recent business highlights (Press release, Ionis Pharmaceuticals, MAY 5, 2021, View Source [SID1234579178]).

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"In the first quarter, we took important steps to maximize the value of our wholly owned pipeline. We recently initiated pivotal studies with our wholly owned FUS-ALS and Alexander disease programs. We delivered positive results from our IONIS-PKK-LRx program, demonstrating its potential to change the standard of care for patients with hereditary angioedema. We also further strengthened the business and continued executing on our strategic priorities," said Brett P. Monia, Ph.D., chief executive officer of Ionis. "This summer, we expect data from our IONIS-MAPTRx program in Alzheimer’s disease patients. And later this year, we look forward to data from the Phase 3 VALOR study of tofersen in patients with SOD1-ALS. If results from the VALOR study are positive, we expect tofersen to be our next commercial medicine. These key upcoming catalysts, together with our recent achievements, position us well to have 12 or more products on the market in 2026."

First Quarter 2021 and Recent Summary Financial Results

On track to achieve 2021 financial guidance reflecting investments in Ionis’ wholly owned pipeline, based on the following first quarter results
$112 million in total revenues
$159 million of operating expenses on a non-GAAP basis(1) and $204 million on a GAAP basis
Net loss of $45 million on a non-GAAP basis(1) and $90 million on a GAAP basis
Further strengthened the Company’s balance sheet with pro forma cash of $2.1 billion, after reflecting the convertible notes transaction
Enables expansion of manufacturing and R&D capacity
$632.5 million principal due in April 2026 with 0% interest and an effective conversion price of $76.39 after the purchase of a call spread
Will realize interest expense savings while keeping potential future dilution nearly flat
Repurchased approximately 80% of previously outstanding 1% convertible notes due in November 2021
"So far this year, we have taken important steps in support of developing and commercializing our wholly owned medicines. In addition to completing the restructuring of our European operations, we expanded our Sobi distribution agreement to include North America. These transactions unlocked significant resources that we are now redirecting towards our highest priority programs, including IONIS-TTR-LRx and IONIS-APOCIII-LRx," said Elizabeth L. Hougen, chief financial officer of Ionis. "We are on track to meet our 2021 financial guidance. In the second half of this year, we expect R&D revenue to increase as many of our partnered programs continue to advance. Importantly, we are well-capitalized with the resources we need to expand our manufacturing and R&D capacity to support the future needs of our wholly owned pipeline. This large capital project, which is now underway, is necessary to successfully execute on our goal to drive growth."

(1)

All non-GAAP amounts referred to in this press release exclude non-cash compensation expense related to equity awards and expenses related to the Akcea acquisition and restructured European operations and the related tax effects. Please refer to the section below titled "Financial Impacts of Akcea Acquisition and Restructured Operations" for a summary of the costs specific to these transactions. Additionally, please refer to the detailed reconciliation of non-GAAP and GAAP measures, which is provided later in this release.

First Quarter 2021 Marketed Products Highlights

SPINRAZA: a global foundation-of-care for the treatment of spinal muscular atrophy (SMA) patients of all ages
$521 million in worldwide sales in the first quarter
More than 11,000 patients worldwide were on therapy at the end of the first quarter across post-marketing, expanded access and clinical trial settings
Higher-dose SPINRAZA demonstrated safety and tolerability consistent with the currently approved dose in the open-label safety cohort of the DEVOTE study, enabling enrollment in the blinded, pivotal cohort to get underway
TEGSEDI and WAYLIVRA: important medicines approved for the treatment of patients with severe rare diseases
Completed the transition of European operations to Swedish Orphan Biovitrum AB (Sobi) and expanded the distribution agreement to include North American TEGSEDI operations
First Quarter 2021 and Recent Pipeline Events

Phase 3 Pipeline: growing and positioned for 12 or more products on the market in 2026
Advanced ION363 into a Phase 3 study in patients with FUS-ALS
Advanced tofersen into the Phase 3 ATLAS study in presymptomatic SOD1-ALS patients
Roche reported tominersen data related to the dosing halt in the Phase 3 program
Mid-stage Pipeline: advancing multiple medicines with potential to change the standard of care for patients with severe diseases
Reported positive topline IONIS-PKK-LRx results in patients with hereditary angioedema
Advanced ION373 into the Phase 2 portion of a pivotal study in patients with Alexander disease
Advanced the IONIS-AGT-LRx development program:
Reported positive Phase 2 data in JACC: Basic to Translational Science
Advanced into a Phase 2b study in patients with hypertension uncontrolled with three or more antihypertensive medications
Advanced into a Phase 2 study in patients with chronic heart failure with reduced injection fraction
Advanced the ongoing Phase 2 study of ION541 in patients with ALS regardless of family history, resulting in a $10 million payment from Biogen
Upcoming 2021 Pipeline Catalysts(2)

(2) Timing of partnered program catalysts based on partners’ most recent publicly available disclosures

First Quarter 2021 Financial Results

TEGSEDI and WAYLIVRA revenue, net

Amortization from upfront payments

20The Company’s commercial revenue in the first quarter of 2021 was consistent with the same period last year. As the Company completes its transition of TEGSEDI operations in North America to Sobi, the Company’s commercial revenue from product sales will shift to distribution fees based on net sales generated by Sobi.

The Company’s R&D revenue decreased in the first quarter of 2021 compared to the same period last year primarily because the Company earned more milestone payments in the first quarter of 2020 than the same period this year. The Company expects its R&D revenue to increase in the second half of 2021 compared to the first half.

Financial Impacts of Akcea Acquisition and Restructured Operations

In conjunction with the Akcea acquisition and restructured European operations, in the first quarter of 2021, the Company incurred $7 million of costs, which it excluded from its non-GAAP amounts for the period. Refer to the detailed reconciliation of non-GAAP and GAAP measures that is provided later in this release. The Company expects to incur additional expenses in the range of $11 million to $14 million related to the restructuring of its North American TEGSEDI operations from the expanded distribution agreement with Sobi. The company will reflect the North American TEGSEDI restructuring costs primarily in the second quarter of 2021.

Operating Expenses

Ionis’ operating expenses for the first quarter of 2021 increased compared to the same period last year driven primarily by the Company’s investments in advancing its late-stage wholly owned pipeline.

Net Loss Attributable to Ionis Common Stockholders

Ionis’ net loss attributable to Ionis’ common stockholders for the first quarter of 2021 increased compared to the same period in the prior year for the reasons discussed above.

Balance Sheet

Ionis ended March 2021 with cash, cash equivalents and short-term investments of $1.8 billion, compared to $1.9 billion at December 31, 2020. In April 2021, Ionis issued $632.5 million of 0% senior convertible notes due in April 2026 and repurchased $247.9 million of its 1% senior convertible notes. After reflecting these transactions, Ionis’ pro forma cash, cash equivalents and short-term investments was $2.1 billion.

The Company revised its 2020 amounts to reflect the simplified convertible instruments guidance the Company adopted retrospectively on January 1, 2021.

Webcast

Today, at 11:30 a.m. Eastern Time, Ionis will conduct a live webcast to discuss this earnings release and related activities. Interested parties may access the webcast here. A webcast replay will be available for a limited time at the same address.