On March 2, 2021 Revolution Medicines, Inc. (Nasdaq: RVMD), a clinical-stage precision oncology company focused on developing targeted therapies to inhibit frontier targets in RAS-addicted cancers, reported its financial results for the fourth quarter and year ended December 31, 2020, and provided a corporate update (Press release, Revolution Medicines, MAR 2, 2021, View Source [SID1234575934]).

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"Revolution Medicines has achieved multiple significant milestones, furthering the company’s position as a leading precision oncology company dedicated to the development of innovative targeted medicines and treatment regimens to address significant unmet needs for patients with RAS-addicted cancers," said Mark A. Goldsmith, M.D., Ph.D., chief executive officer and chairman of Revolution Medicines.

"Our exceptional team delivered two pioneering RAS(ON) inhibitor development candidates into IND-enabling development, RMC-6291 and RMC-6236. RMC-6291 targets the oncogenic KRASG12C(ON) variant through a highly differentiated anti-tumor profile. RMC-6236 uniquely targets numerous RAS(ON) variants responsible for many cancers. We believe these two development candidates hold great promise for potential use in treating patients with a diverse range of RAS-addicted cancers, and we are actively advancing both toward the clinic.

"The company has also made great progress with our RAS Companion Inhibitor portfolio. Our most advanced candidate RMC-4630, a SHP2 inhibitor, is being evaluated in multiple studies to position it as a backbone for targeted combination therapies. We received FDA clearance to begin clinical evaluation of RMC-5552, a potent mTORC1-selective inhibitor, and plan to initiate a monotherapy dose-escalation study imminently. Additionally, we have advanced RMC-5845, our potent, selective, oral inhibitor of SOS1, a major switch in the cycling of RAS(OFF) to RAS(ON), into IND-enabling development.

"To support our expanded and advancing pipeline of development programs, Revolution Medicines recently completed an upsized financing, raising net proceeds of $281 million. We have made tremendous progress as a company and believe that our cohesive portfolio of innovative clinical and preclinical assets will permit rational, mechanism-based combinations and position Revolution Medicines to fulfill our mission."

R&D Highlights

RAS(ON) Inhibitors – Revolution Medicines continues maturing its first-in-class RAS(ON) platform, introducing an expansive collection of tri-complex inhibitors targeting diverse oncogenic RAS variants through highly differentiated chemical and pharmacologic profiles.

Pioneering RAS(ON) assets, RMC-6291 (KRASG12C) and RMC-6236 (RASMULTI), enter IND-enabling development
○ RMC-6291 is a first-in-class, potent, oral and selective tri-complex inhibitor of KRASG12C(ON) and NRASG12C(ON) that has demonstrated deep and sustained anti-tumor activity in preclinical lung cancer models driven by a KRASG12C mutation. The company expects to submit an investigational new drug application (IND) for RMC-6291 in the first half of 2022.

○ RMC-6236 is a first-in-class, potent, oral RAS-selective tri-complex, RASMULTI(ON) inhibitor that has demonstrated pronounced anti-tumor activity in preclinical models of human lung, colorectal and pancreatic cancers caused by multiple RAS variants for which no targeted treatment is currently available. The company expects to submit an IND for RMC-6236 in the first half of 2022.

Continued expansion of other RAS(ON) inhibitor programs – Revolution Medicines continues to progress an expanding portfolio of potent, cell-active RAS(ON) inhibitors with the potential to target RAS variants driving the vast majority of RAS-addicted cancers. In particular, the company’s KRASG12D- and KRASG13C-selective programs continue to advance in lead optimization. The company expects to nominate a third development candidate from its RAS(ON) inhibitor portfolio in the second half of 2021.
RAS Companion Inhibitors – Revolution Medicines continues to advance and expand multiple clinical studies both as monotherapy and in targeted drug combinations designed to achieve maximum clinical benefit.

RMC-4630 (SHP2 Inhibitor) – RMC-4630 is a potent, oral, selective inhibitor of the SHP2 protein, a central node in the RAS signaling pathway. Its development is being advanced in partnership with, and is primarily funded by, Sanofi.
○ RMC-4630 monotherapy has shown initial clinical anti-tumor activity in multiple cancer genotypes. The company has initiated an expansion cohort at the single agent recommended Phase 2 dose and schedule (RP2DS). The company expects to disclose a safety data set from the dose escalation portion of this trial in the first half of 2021.

○ RMC-4630 in combination with cobimetinib (Cotellic) has shown initial clinical activity in patients with colorectal cancer driven by KRAS mutations. The company has initiated expansion cohorts evaluating patients with KRASMUTANT colorectal cancer at the RP2DS for this combination. The company expects preliminary safety and clinical activity data from this expansion study in 2022.

○ Studies evaluating RMC-4630 in combination with multiple inhibitors continue and are expanding.

▪ Dosing and enrollment continue in the Amgen-sponsored Phase 1 study of RMC-4630 in combination with Amgen’s KRASG12C(OFF) inhibitor, AMG 510, or sotorasib. The company expects a RP2DS will be reached in the first half of 2021 with preliminary activity data in the second half of 2021.

▪ Dosing and enrollment continue in the Sanofi-sponsored Phase 1 study of RMC-4630 in combination with the PD-1 inhibitor, pembrozilumab (Keytruda). The company expects a RP2DS will be reached for this combination in the first half of 2021.

▪ Dosing and enrollment continue in the Phase 1 study of RMC-4630 in combination with the EGFR inhibitor, osimertinib (Tagrisso). The company expects initial tolerability and pharmacokinetic (PK) data from this combination in the second half of 2021.

▪ Announced a clinical collaboration agreement with AstraZeneca to study RMC-4630 in combination with an emerging asset targeting KRASG12C from AstraZeneca’s portfolio.

RMC-5552 (mTORC1/4EBP1 Inhibitor) – RMC-5552 is a potent mTORC1- selective inhibitor.
○ Received FDA clearance and initiation of clinical sites for Phase 1 monotherapy dose-escalation study is underway. The company expects to begin dosing patients with monotherapy in the first half of 2021 with initial safety, PK and single agent activity data expected in 2022.

○ The company intends to evaluate RMC-5552 in combination therapies with RAS inhibitors for patients with cancers harboring RAS/mTOR signaling co-mutations.

RMC-5845 (SOS1 Inhibitor) – RMC-5845 is a potent, selective, oral inhibitor of SOS1, a major switch in the cycling of RAS(OFF) to RAS(ON).
○ The company intends to evaluate RMC-5845 for treatment of certain genetically defined RAS-dependent cancers.

○ Recently advanced into IND-enabling development. The company expects to submit an IND in the second half of 2021.

Corporate Highlights

Completed upsized financing to strengthen balance sheet and support advancement of expanding pipeline – The company completed a public offering of common stock in February 2021, raising net proceeds of $281 million. The company plans to use these proceeds to advance the company’s wholly-owned assets into clinical development.
Sanofi collaboration continues to make progress – The company’s funded collaboration with Sanofi for the clinical development of RMC-4630 continues to advance RMC-4630 as a backbone of combination therapy in RAS-addicted cancers.
Fourth Quarter and Full Year 2020 Financial Highlights

Cash Position: Cash, cash equivalents and marketable securities were $440.7 million as of December 31, 2020, compared to $122.8 million as of December 31, 2019. The increase was primarily due to proceeds from the company’s initial public offering in February 2020 and follow-on equity public offering in July 2020. Proceeds from the recently completed offering are not included in the December 31, 2020 cash, cash equivalents and marketable securities balance.

Revenue: Total revenue, consisting of revenue from the company’s collaboration agreement with Sanofi, was $8.8 million for the quarter ended December 31, 2020, compared to $12.1 million for the quarter ended December 31, 2019. Total revenue was $43.0 million for the year ended December 31, 2020, compared to $50.0 million for the year ended December 31, 2019. The decrease was due to lower reimbursed research and development services for RMC-4630 resulting from lower manufacturing costs. During the quarter and year ended December 31, 2019, the company incurred upfront manufacturing costs related to the supply of RMC-4630 for our clinical trials.

R&D Expenses: Research and development expenses were $37.0 million for the quarter ended December 31, 2020, compared to $27.5 million for the quarter ended December 31, 2019. Research and development expenses were $132.3 million for the year ended December 31, 2020, compared to $91.8 million for the year ended December 31, 2019. The increase was primarily due to an increase in research expenses associated with the company’s pre-clinical research portfolio, an increase in personnel-related expenses related to additional headcount, and an increase in stock-based compensation, partially offset by lower costs related to RMC-4630.

G&A Expenses: General and administrative expenses were $5.8 million for the quarter ended December 31, 2020, compared to $4.2 million for the quarter ended December 31, 2019. General and administrative expenses were $21.4 million for the year ended December 31, 2020, compared to $12.4 million for the year ended December 31, 2019. The increase was primarily due to an increase in expenses associated with operating as a public company, an increase in personnel-related expenses related to additional headcount, and an increase in stock-based compensation.

Net Loss: Net loss was $34.2 million for the quarter ended December 31, 2020, compared to net loss of $14.6 million for the quarter ended December 31, 2019. Net loss was $108.2 million for the year ended December 31, 2020, compared to net loss of $47.7 million for the year ended December 31, 2019.

2021 Financial Guidance

Revolution Medicines expects full year 2021 GAAP net loss to be between $170 million and $190 million, which includes estimated non-cash stock-based compensation expense of $20 million to $25 million.

On March 2, 2021 Five Prime Therapeutics, Inc. (NASDAQ: FPRX), reported its fourth quarter and full year 2020 operational and financial results on Wednesday, March 10, 2021 after the U.S. financial markets close (Press release, Five Prime Therapeutics, MAR 2, 2021, View Source [SID1234575933]). Five Prime will also host a conference call and live audio webcast that same day at 4:30 p.m. (ET) / 1:30 p.m. (PT) to provide a general business update and discuss the company’s financial results.

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The live audio webcast may be accessed through the "Events & Presentations" page in the "Investors" section of the company’s website at www.fiveprime.com. Alternatively, participants may dial (877) 878-2269 (domestic) or (253) 237-1188 (international) and refer to conference ID: 9872966.

The archived conference call will be available on Five Prime’s website beginning approximately two hours after the event and will be archived and available for replay for at least 30 days after the event.

On March 2, 2021 Aptose Biosciences Inc. (Nasdaq: APTO; TSX: APS), a clinical stage company developing highly differentiated therapeutics that target the underlying mechanisms of cancer, reported that it will release its financial results for the year and quarter ended December 31, 2020, on Tuesday, March 23, 2021 after the close of the market (Press release, Aptose Biosciences, MAR 2, 2021, View Source [SID1234575932]).

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The live conference call can also be accessed through a link on the Investor Relations section of Aptose’s website at View Source An archived version of the webcast along with a transcript will be available on the company’s website for 30 days.

The press release, the financial statements and the management’s discussion and analysis for the year and quarter ended December 31, 2020 will be available on SEDAR at www.sedar.com and EDGAR at www.sec.gov/edgar.shtml.

On March 2, 2021 Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) reported financial results for the fourth quarter and full year ended December 31, 2020, 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, MAR 2, 2021, View Source [SID1234575931]).

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"Our team has shown its resilience as we continue to execute on our mission to serve patients who have diseases where few or no approved treatment options exist," said Raul Rodriguez, Rigel’s president and CEO. "Despite the challenges brought on by 2020, we successfully expanded our global ITP reach and positioned ourselves for potential success in wAIHA, announced a major collaboration with Lilly to develop RIP1 inhibitors, and launched a comprehensive COVID-19 clinical program which has gained the support from the NIH, DOD, and several universities. Importantly, we also continued to explore opportunities in immunology, and more recently heme-onc, with our IRAK 1/4 inhibitor program."

Business Update
In February 2021, Rigel and Eli Lilly (Lilly) announced a global strategic collaboration to co-develop and commercialize R552, Rigel’s receptor-interacting serine/threonine-protein kinase 1 (RIP1) inhibitor, for all indications, including autoimmune and inflammatory diseases. In addition, Lilly will lead the development and commercialization of all RIP1 inhibitors in central nervous system (CNS) indications. Under the terms of the agreement, Lilly will pay an upfront cash payment to Rigel of $125 million and is eligible to receive up to $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 launched a Phase 3 clinical trial to evaluate fostamatinib for the treatment of hospitalized COVID-19 patients. The Phase 3 trial is designed to evaluate the safety and efficacy of fostamatinib in hospitalized COVID-19 patients without respiratory failure that have certain high-risk prognostic factors. This multi-center, double-blind, placebo-controlled, adaptive design study is expected to enroll over 300 evaluable patients that will be randomly assigned 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.

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 Rigel’s Phase 3 clinical trial of fostamatinib in hospitalized COVID-19 patients.

The Phase 2 clinical trial of fostamatinib in hospitalized COVID-19 patients sponsored by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health (NIH), in collaboration with Inova Health System has currently enrolled 57 patients. This is a double-blind, placebo-controlled Phase 2 clinical trial that is randomly assigning fostamatinib plus standard of care (SOC) or matched placebo plus SOC (1:1) to approximately 60 evaluable patients who are a 5 to 7 on the 8-point ordinal scale (requiring supplemental oxygen via nasal canula or non-invasive ventilation, requiring mechanical ventilation or extracorporeal membrane oxygenation). The primary endpoint of this study is cumulative incidence of serious adverse events (SAE) through day 29. The NHLBI and Rigel expect to report topline data from this clinical trial in April 2021.

Imperial College London’s ongoing Phase 2 clinical trial of fostamatinib in hospitalized COVID-19 patients is a two-stage open label, controlled trial with patients randomized (1:1:1) to fostamatinib, ruxolitinib, or standard of care. The study has currently enrolled 106 patients. Treatment will be administered twice daily for 14 days and patients will receive a follow-up assessment at day 14 and day 28 after the first dose. The primary objective will be to determine the efficacy of fostamatinib and the efficacy of ruxolitinib compared to standard of care to reduce the proportion of hospitalized patients progressing from mild or moderate to severe COVID-19 pneumonia.

Enrollment is progressing in Rigel’s FORWARD study, a Phase 3 pivotal trial of TAVALISSE in warm autoimmune hemolytic anemia (wAIHA). The study has enrolled 66 of 90 patients targeted for enrollment. Rigel has reached agreement with the U.S. Food and Drug Administration (FDA) on the durable response measure for the primary efficacy endpoint of the study as well as the inclusion of additional secondary endpoints. The company recently announced that the FDA had granted Fast Track designation to TAVALISSE for the treatment of wAIHA. The FDA previously granted TAVALISSE Orphan Drug designation for this indication. If approved, TAVALISSE may be the first-to-market therapy for patients with wAIHA.

Rigel continues to advance the development of its IRAK1/4 program, which includes R835, an orally available, potent and selective inhibitor that inhibits both IRAK1 and IRAK4. The company is currently identifying therapeutic opportunities in the areas of hematology/oncology and rare immunology diseases.

In November 2020, Rigel and its partner Medison Pharma announced that Health Canada approved the new drug submission (NDS) for TAVALISSE for the treatment of thrombocytopenia in adult patients with chronic ITP who have had an insufficient response to other treatments. Medison is also anticipating a decision on a New Drug Application (NDA) in Israel in Q2 2021. In July 2020, Rigel and its partner Grifols S.A. announced the launch of TAVLESSE in Germany and the United Kingdom following approval by the European Commission in January 2020. Currently, TAVALISSE is in a Phase 3b clinical trial in Japan with Rigel’s partner Kissei. This trial is required for approval by the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan.

Financial Update
For the fourth quarter of 2020, Rigel reported a net loss of $19.2 million, or $0.11 per share, compared to net loss of $17.2 million, or $0.10 per share, in the same period of 2019.

In the fourth quarter of 2020, total revenues were $18.5 million, consisting of $17.8 million in TAVALISSE net product sales and $697,000 in contract revenues from collaborations. TAVALISSE net product sales of $17.8 million increased by 28% from $13.8 million in the fourth quarter of 2019. Contract revenues from collaborations of $697,000 for the fourth quarter of 2020 consisted of $500,000 from Grifols related to an option for commercialization in additional territories and $197,000 in revenues earned from the performance of certain research and development services from Rigel’s collaboration agreement with Grifols.

Rigel reported total costs and expenses of $37.3 million in the fourth quarter of 2020, compared to $32.7 million for the same period in 2019. The increase in costs and expenses was due to the increase in research and development costs primarily related to the continued work on Rigel’s Phase 1 clinical trial in IRAK 1/4 inhibitor program, as well as its recently launched Phase 3 clinical trial for hospitalized COVID-19 patients, partially offset by the decrease in costs on Rigel’s ongoing Phase 3 clinical trial in wAIHA.

For the full year ended December 31, 2020, Rigel reported a net loss of $29.7 million, or $0.18 per share, compared to a net loss of $66.9 million, or $0.40 per share, for the same period of 2019.

Rigel reported total revenues of $108.6 million for the year ended December 31, 2020, compared to $59.3 million in the same period of 2019. Total revenues for the year ended December 31, 2020 consisted of $61.7 million in TAVALISSE net product sales and $46.9 million in contract revenues from collaborations. TAVALISSE net product sales of $61.7 million increased by 41% from $43.8 million in 2019. The increase in contract revenues from collaborations related to revenue from the upfront fee previously received in 2019, as well as the milestone payment received from Grifols in the first quarter of 2020 upon EC approval of the MAA for fostamatinib in Europe, and the $2.1 million in contract revenues for the achievement of a milestone in accordance with the amended license and collaboration agreement with Daiichi-Sankyo, partially offset by the developmental and commercial milestones from its various collaborative partners in 2019.

Total costs and expenses for the year ended December 31, 2020, were $137.6 million, compared to $128.4 million, for the same period of 2019. The increase in total costs and expenses was primarily related to the increases in research and development costs due to the completion of Rigel’s Phase 1 clinical trial in RIP1 inhibitor program, ongoing work on recently launched Phase 3 clinical trial for hospitalized COVID-19 patients, continued work on Rigel’s Phase 1 clinical trial in IRAK 1/4 inhibitor program and ongoing Phase 3 clinical trials in wAIHA, as well as increases in personnel-related costs, partially offset by decreases in various third-party costs due to the COVID-19 pandemic.

As of December 31, 2020, Rigel had cash, cash equivalents and short-term investments of $57.3 million, compared to $98.1 million as of December 31, 2019.

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.

About R5526
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 R8356
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 March 2, 2021 Navidea Biopharmaceuticals, Inc. (NYSE American: NAVB) ("Navidea" or the "Company"), a company focused on the development of precision immunodiagnostic agents and immunotherapeutics, reported that management will present a company overview and hold virtual meetings with investors at the H.C. Wainwright Global Life Sciences Virtual Conference being held March 9-10, 2021 (Press release, Navidea Biopharmaceuticals, MAR 2, 2021, View Source [SID1234575930]).

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The Navidea presentation can be accessed by registering for the H.C. Wainwright Global Life Sciences Virtual Conference here. The webcast will be available on the H.C. Wainwright Conference Portal beginning March 9, 2021 at 7:00 a.m. Eastern time through March 10, 2021 at 9:00 p.m. Eastern time. The Company’s corporate presentation can be accessed from the Investor Relations section of the Company website here.