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BIOLASE, Inc. Announces Closing of $6.9 Million Registered Direct Offering Priced At-The-Market

On June 11, 2020 BIOLASE, Inc. (NASDAQ: BIOL), the global leader in dental lasers, reported the closing on June 10, 2020 of its previously announced registered direct offering of approximately $6.9 million of its common stock in a registered direct offering priced at-the-market under Nasdaq rules and warrants to purchase common stock in a concurrent private placement (Press release, Biolase Technology, JUN 11, 2020, View Source [SID1234561023]). The combined purchase price for one share of common stock and warrant to purchase one share of common stock was $0.64. BIOLASE intends to use the net proceeds for working capital and for other general corporate purposes.

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Under the terms of the securities purchase agreement, BIOLASE sold 10,800,000 shares of common stock. In a private placement, which was consummated concurrently with the offering, BIOLASE issued warrants to purchase up to an aggregate of 10,800,000 shares of common stock. The warrants are immediately exercisable, will expire 5 years from the date of issuance and have an exercise price of $0.515 per common share.

Maxim Group LLC, The Benchmark Company, LLC and Colliers Securities LLC acted as co-placement agents for the offering.

The shares of common stock were offered pursuant to a shelf registration statement on Form S-3 (File No. 333-233172) previously declared effective by the SEC on August 23, 2019. The offering of the shares of common stock was made by means of a prospectus supplement that was filed with the SEC and forms a part of the registration statement.

BIOLASE intends to move forward with a proposed rights offering in the next few weeks. BIOLASE believes that the capital raised in this registered direct offering bolsters its balance sheet and will enable it to approach the proposed rights offering from an enhanced liquidity and capitalization position. BIOLASE previously filed a registration statement on Form S-1 (File No. 333-238914) with respect to the proposed rights offering with the SEC.

Zimmer Biomet Announces Quarterly Dividend for Second Quarter of 2020

On June 11, 2020 Zimmer Biomet Holdings, Inc. (NYSE and SIX: ZBH), a global leader in musculoskeletal healthcare, reported that its Board of Directors has approved the payment of a quarterly cash dividend to stockholders for the second quarter of 2020 (Press release, Zimmer Holdings, JUN 11, 2020, View Source [SID1234561022]).

The cash dividend of $0.24 per share is payable on July 31, 2020 to stockholders of record as of the close of business on June 29, 2020.

Medicenna to Present at Raymond James Human Healthcare Innovation Conference

On June 11, 2020 Medicenna Therapeutics Corp. ("Medicenna" or the "Company") (TSX: MDNA) (OTCQB: MDNAF), a clinical stage immuno-oncology company, reported that Dr. Fahar Merchant, President, CEO and Chairman of the Board of Medicenna, will present a corporate overview at the Raymond James 2020 Human Healthcare Innovation Conference on Thursday, June 18th, 2020, at 1:40 PM ET (Press release, Medicenna Therapeutics, JUN 11, 2020, View Source [SID1234561021]).

A live webcast of the presentation may be accessed at View Source A replay of the presentation will be available after the event by visiting the Investor Relations section of Medicenna’s website at View Source

Kymera Therapeutics to Disclose IRAKIMiD Degrader Program and Present Preclinical Data Demonstrating Potent Immunomodulatory and Antitumor Activity for its Novel STAT3 Degraders in Immuno-oncology

On June 11, 2020 Kymera Therapeutics, Inc., a biotechnology company pioneering targeted protein degradation to invent breakthrough protein degrader medicines for patients, reported that it will present preclinical data on its potent and highly selective STAT3 degraders as well as the first data from its novel IRAKIMiD degraders combining IRAK4 and IMiD substrate degradation (Press release, Kymera Therapeutics, JUN 11, 2020, View Source [SID1234561020]). Data will be shared in two separate presentations (Abstracts #10165 and #4349, respectively) during the 2020 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II on Monday, June 22 at 9:00 AM EDT.

STAT3 is an attractive but elusive target known to regulate genes implicated in oncogenesis, tumor immune evasion, inflammation and fibrosis. In cancer, STAT3 has been shown to drive tumor growth and promote an immunosuppressive tumor microenvironment (TME). Kymera has previously reported the ability of its highly selective STAT3 degraders to achieve tumor regression in mouse xenograft models of STAT3-dependent hematologic malignancies. The company will present preclinical data demonstrating that its STAT3 degraders downregulated immune checkpoint signals on tumor cells and positively modulated composition and activity of immune cells in the TME, leading to in vivo antitumor activity in a solid tumor model refractory compared to standard anti-PD-1/L1 immunotherapy. These findings demonstrate the potential for STAT3 degraders to drive antitumor responses through both tumor cell-intrinsic and -extrinsic immunomodulation as well as direct antitumor effects.

Kymera will also present the first data from its potent IRAKIMiD degraders in development for the treatment of MYD88-mutant lymphomas, which constitute approximately one quarter of all diffuse large B-cell lymphomas (DLBCL). IRAKIMiDs are novel heterobifunctional degraders that target degradation of both IRAK4 and IMiD substrates with a single small molecule. While IRAK4 degradation alone offers a viable therapeutic approach that we believe is superior to IRAK4 kinase inhibition, targeting two complementary pathways in lymphoma biology addresses potential tumor escape mechanisms and shows synergistic activity in MYD88-mutant lymphomas compared to IRAK4 degraders or IMiDs alone. In fact, IRAKIMiDs demonstrated improved cell death and breadth of activity relative to IMiDs or IRAK4-selective degraders, and drove strong in vivo tumor regressions in multiple models of MYD88-mutant B cell lymphoma that Kymera believes are superior to what has been observed in preclinical studies with other agents such as BTK inhibitors and IMiDs.

"Our STAT3 and IRAKIMiD programs exemplify the tremendous potential of targeted protein degradation in oncology, allowing us to inhibit well-validated, high impact disease pathways through targets like STAT3 previously considered undruggable, and through selective multi-targeting of IRAK4 and IMiD substrates with a single degrader," said Jared Gollob, MD, Chief Medical Officer. "The dual effects of STAT3 degraders on both tumor cells and the tumor microenvironment, as well as the dual effects of IRAKIMiDs on multiple pathways involved in tumor cell growth and survival in MYD88-mutant lymphomas, drive robust antitumor responses in preclinical models that support progression of both programs into the clinic in 2021."

AACR Study Highlights

ABSTRACT #10165 / POSTER #LB-088, "A STAT3 selective targeted protein degrader decreases the immune-suppressive tumor microenvironment and drives antitumor activity in preclinical models," presented by Fred Csibi, PhD, Associate Director, Oncology Biology at Kymera Therapeutics.

KTX-201 (formerly known as KYM-003) is a potent and highly selective STAT3 degrader with activity in immune and tumor cells.
Degradation of STAT3 with KTX-201 in both immune and tumor cells reversed expression of genes that contribute to immune suppression.
KTX-201 treatment resulted in reversal of immunosuppression in an in vitro non-small cell lung cancer model as well as antitumor activity in a mouse colorectal cancer model resistant to immune checkpoint inhibitors.
ABSTRACT #4349 / POSTER #5222, "Degraders targeting both IRAK4 and IMiD substrates show combinatorial effects leading to broader activity with durable and complete regressions in MYD88 mutant lymphoma xenografts in vivo," presented by Duncan H. Walker, PhD, VP of Oncology at Kymera Therapeutics.

IRAK4 degradation, but not IRAK4 kinase inhibition, showed additive and synergistic activity with IMiDs in vitro; IRAKIMiDs, which combine these activities in a single molecule, showed potent in vitro and in vivo activity.
Degradation of both IRAK4 and IMiD substrates correlated with in vitro cell growth inhibition, consistent with a requirement for both activities for cell death.
Regressions observed in xenograft models of MYD88-mutant lymphoma were associated with degradation of both IRAK4 and IMiD substrates, consistent with the dual-targeting activities of these molecules.

Rigel to Present Poster Highlighting TAVALISSE at the Virtual Edition of the 25th European Hematology Association (EHA) Annual Congress

On June 11, 2020 Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) reported that data related to TAVALISSE (fostamatinib disodium hexahydrate) tablets will be highlighted in a presentation at the Virtual Edition of the 25th EHA (Free EHA Whitepaper) Annual Congress taking place June 11-21, 2020 (Press release, Rigel, JUN 11, 2020, View Source [SID1234561019]). The presentation will be made available on the event’s website at www.ehaweb.org/congress/ on Friday, June 12 at 8:30 am CEST.

In this previously presented post-hoc analysis, 32 patients received TAVALISSE as a second-line therapy, and 78% (25/32) achieved ≥1 platelet count of ≥50,000/µL (without rescue therapy). Adverse events were manageable and consistent with those previously reported with fostamatinib.

Fostamatinib disodium hexahydrate is an oral drug designed to inhibit spleen tyrosine kinase (SYK), a key signaling component of the body’s immune process that leads to platelet destruction in immune thrombocytopenia (ITP) and proposed red blood cell destruction in warm autoimmune hemolytic anemia (wAIHA). Fostamatinib is commercially available in the U.S. under the brand name TAVALISSE (fostamatinib disodium hexahydrate) tablets and is the first and only SYK inhibitor indicated for the treatment of thrombocytopenia in adult patients with chronic ITP who have had an insufficient response to a previous treatment. TAVALISSE is currently being investigated in a Phase 3 trial for the treatment of wAIHA, a rare, serious blood disorder for which there are no approved therapies.

Poster Presentation
Abstract #EP1625
Second-line Therapy for Immune Thrombocytopenia with the Spleen Tyrosine Kinase Inhibitor Fostamatinib
Presenter: Dr. Nichola Cooper
Session Topic: 32. Platelets Disorders

About ITP
In patients with ITP, 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 this disease 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 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 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.