On October 23, 2019 Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) reported a business update that will be discussed in more detail on the company’s investor and analyst call to be held today at 10am Eastern Time / 7am Pacific Time (Press release, Rigel, OCT 23, 2019, View Source [SID1234542441]).

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"This is an exciting time for Rigel with significant advancements in all segments of our business," said Raul Rodriguez, Rigel’s president and CEO. "We continue to grow sales of TAVALISSE in the U.S. and are making substantial strides in expanding our pipeline. Our clinical development efforts will be led by our newly appointed chief medical officer, Dr. Wolfgang Dummer. We are excited to leverage his experience and depth of knowledge as we continue to pursue our clinical development goals."

Business Update Highlights

TAVALISSE Revenues Increase

Preliminary estimates indicate that TAVALISSE (fostamatinib disodium hexahydrate) net product sales continued to achieve double digit quarter over quarter growth, increasing 15% to $11.7 million from $10.2 million in the second quarter of 2019. This information is preliminary, has not been audited and is subject to change upon completion of Rigel’s closing procedures.

IRAK1/4 Program Shows Proof-of-Mechanism in Humans

Rigel completed a Phase 1 clinical trial of R835, an interleukin-1 receptor-associated kinase 1/4 (IRAK 1/4) inhibitor. In addition to positive tolerability and pharmacokinetic data, R835 showed consistent inhibition of cytokine production in an LPS (lipopolysaccharide) challenge which was designed to gauge the molecule’s impact on inflammatory stimulation.

New RIP1 Inhibitor Program

For the first time today, Rigel announced its new receptor-interacting protein kinase (RIP1) inhibitor program. The lead molecule, R552, has initiated a Phase 1 clinical trial. RIP1 is believed to be a key driver of necroptosis which is implicated in a broad range of key inflammatory cellular processes including cell death and cytokine production.

Appointment of Wolfgang Dummer, MD, PhD as CMO

The Company is pleased to announce the appointment of Wolfgang Dummer, MD, PhD to the role of Chief Medical Officer. Dr. Dummer has more than 20 years of clinical and drug development experience at world class institutions, as well as an extensive academic history. Most recently, he served as Chief Medical Officer at Aridis Pharmaceuticals, Inc. where he was responsible for overseeing all aspects of drug development in the field of antimicrobial immunotherapy. Prior to that, he served as Vice President of Clinical Development at BioMarin Pharmaceutical Inc., where he led the development of a deep rare disease pipeline, including the company’s leading marketed product, Vimizim (elosulfase alpha). Prior to Biomarin, Dr. Dummer served for 11 years in capacities of increasing importance in Clinical Research and Development at Genentech, Inc. (now part of Roche), overseeing numerous programs, including Rituximab. Dr. Dummer is a board-certified clinical dermatologist and allergist/immunologist. Over the course of his career, he has published more than 50 peer reviewed journal articles and has more than 40 abstracts, presentations, and book contributions.

Business Update Conference Call

As previously announced, Rigel will host a conference call today to provide a business update. 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 Rigel’s website at www.rigel.com. The webcast will be archived and available for replay for 90 days 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 R8351

R835 is an oral investigational candidate that is a potent and selective inhibitor of IRAK1 and IRAK4 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 conditions. Dysregulation of the TLR and IL-1R pathways may be associated with a variety of inflammatory conditions including psoriasis, rheumatoid arthritis, lupus and gout (among others).

About R5521

R552 is an investigational candidate that is a receptor-interacting protein kinase (RIP1) inhibitor. RIP1 is believed to play a critical role in necroptosis, a type of regulated cell death. In necroptosis, cells rupture leading to the dispersion of cell contents, which signals an immune response and enhances inflammation. It is implicated in a broad range of key inflammatory cellular processes including cell death and cytokine production. In preclinical studies, R552 showed prevention of joint and skin inflammation in a RIP1-mediated murine model of inflammation and tissue damage.

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.