On December 4, 2020 Reata Pharmaceuticals, Inc. (Nasdaq: RETA) ("Reata" or the "Company"), a clinical-stage biopharmaceutical company, reported the closing of its previously announced underwritten public offering of 2,000,000 shares by the Company of its Class A common stock, at a price to the public of $140.85 per share, for gross proceeds of $281.7 million (Press release, Reata Pharmaceuticals, DEC 4, 2020, View Source [SID1234572231]). Reata has granted the underwriters a 30-day option to purchase 300,000 additional shares of its Class A common stock, on the same terms and conditions as the shares offered in the public offering.

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Barclays Capital Inc. and Goldman Sachs & Co. LLC acted as the joint book-running managers for the offering.

The securities described above were offered pursuant to an automatically effective shelf registration statement on Form S-3. The offering was conducted only by means of a written prospectus and prospectus supplement that form a part of the registration statement. A final prospectus supplement and accompanying prospectus relating to the offering have been filed with the Securities and Exchange Commission (the "SEC") and are available on the SEC’s website at www.sec.gov. Copies of the final prospectus supplement and the accompanying prospectus may also be obtained by request at Barclays Capital Inc., Attention: Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, New York 11717, telephone: 1-888-603-5847, or by emailing [email protected]; or Goldman Sachs & Co. LLC, Prospectus Department, 200 West Street, New York, NY 10282, telephone: 1-866-471-2526, facsimile: 212-902-9316 or by emailing [email protected].

This news release is for informational purposes only and shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities, in any state or jurisdiction in which such offer, solicitation or sale of these securities would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On December 3, 2020 Johnson & Johnson’s BCMAxCD3 bispecific antibody teclistamab reported that it has achieved a 73% overall response rate in a small trial of heavily pretreated multiple myeloma patients (Press release, Johnson & Johnson, DEC 4, 2020, View Source [SID1234572213]).

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J&J presented data on an intravenous version of the drug in May, revealing eight of the 12 patients to get a certain dose responded to the therapy. Since then, J&J has moved a subcutaneous formulation of the bispecific antibody into a pivotal phase 2 clinical trial. J&J arrived at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2020 Annual Meeting with data to support its decision to advance the formulation.

Sixteen of the 22 patients to receive the 1500 µg/kg subcutaneous phase 2 dose responded. Five participants had complete responses. All bar one of the responders was progression-free after median follow-up of 3.9 months.

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J&J achieved those responses without causing significant toxicity. While 64% of patients on the phase 2 subcutaneous dose experienced cytokine release syndrome, all those events were grade 1 or 2 and none caused a patient to discontinue. There was one grade 1, reversible neurotoxicity event. The mix of efficacy and tolerability seen to date has persuaded J&J to up its bet on teclistamab.

"It’s still early … but certainly the profile of teclistamab looks very, very promising to us and one that is worthy of aggressive investment and development. That’s the approach that we’re taking now," said Craig Tendler, vice president, oncology clinical development and global medical affairs at J&J.

An analysis of 11 patients who had complete responses to either the intravenous or subcutaneous formulations showed eight participants were minimal residual disease-negative at a threshold of 10-6.

The responses, which J&J said deepened over time, were seen in patients failed by multiple other therapies. Across the study, patients had received a median of six prior lines of treatment. Almost 40% of the participants were refractory to two or more immunomodulatory agents, two or more proteasome inhibitors and an anti-CD38 therapy. Such patients have few treatment options today.

"To be able to have a well-tolerated antibody be given that can get them into a very fast remission — time to first response is also quite quick — is certainly an important milestone for these patients in terms of getting their disease under control," Tendler said.

J&J is one of a considerable number of drug developers targeting BCMA to give relapsed/refractory multiple myeloma patients new options. Amgen, Bristol-Myers Squibb, Pfizer and Regeneron all have anti-BCMA bispecifics in development, GlaxoSmithKline is closing in on approval of an antibody-drug conjugate aimed at the target and a clutch of companies, including J&J, are working on cell therapies.

Initially, J&J, like its rivals, is going after heavily pretreated patients but it plans to move into earlier lines of therapy. J&J is testing the bispecific in combination with its anti-CD38 blockbuster Darzalex and has aspirations to establish it as a maintenance therapy and in the smoldering myeloma space. The switch from intravenous to subcutaneous formulations could benefit J&J’s push into other parts of the treatment pathway, including by enabling it to move away from weekly dosing.

"We have cohorts that will be looking at bi-weekly and then ultimately monthly dosing. That is definitely in the plan for further optimization of dosing, especially in settings like maintenance therapy. We want to have the most flexible dosing schedule so that this is not inconvenient for patients," Tendler said.

With other companies posting encouraging data and looking at subcutaneous formulations, J&J will face competition as it seeks to establish teclistamab but approaches the challenge on the back of its success reshaping multiple myeloma treatment with Darzalex.

On December 4, 2020 PharmaEngine, Inc. (TWO: 4162) reported that it has entered into a Collaboration and License Agreement with UK-based Sentinel Oncology Limited for advancing the new drug development of SOL-578, a Checkpoint Kinase 1 (Chk1) inhibitor, under which PharmaEngine will fund the IND enabling studies for SOL-578 (Press release, PharmaEngine, DEC 4, 2020, View Source [SID1234572188]).

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Sentinel Oncology Limited is a drug discovery company passionate about the development of novel therapeutics to treat cancer patients for whom there is currently an unmet medical need. The company’s mission is to increase survival and improve outcomes for cancer patients with CNS tumors. SOL-578 is a best-in-class checkpoint kinase 1 (Chk1) inhibitor featuring high kinase selectivity and oral bioavailability which targets the DNA Damage Response (DDR) network.

Under the terms of the Agreement, Sentinel Oncology will receive an exclusivity payment and PharmaEngine will obtain an option to receive the exclusive rights to develop and commercialize SOL-578 worldwide. In the event that PharmaEngine completes the IND enabling studies and exercise its option, Sentinel Oncology will be eligible to receive an upfront payment and development milestone payments in addition to tiered royalties based on future worldwide net sales of SOL-578.

"We are happy to collaborate with Sentinel Oncology Limited to activate the development of SOL-578." said Yufang Hu, Ph.D., President and CEO of PharmaEngine, Inc., "We are attracted by the dual function of SOL-578 in targeting the DDR signaling and cell cycle regulation axis in cancers. We believe that PharmaEngine can accelerate the development of this product based on our successful experience with a liposomal irinotecan, Onivyde."

About SOL-578

SOL-578 is a best-in-class checkpoint kinase 1 (Chk1) inhibitor featuring high kinase selective and oral bioavailability which targets the DNA Damage Response (DDR) network. Checkpoint kinases play a crucial role in the cellular response to DNA damage. Chk1 inhibitors potentiate the DNA-damaging effects of cytotoxic therapies and/or promote elevated levels of replication stress, leading to tumor cell death. SOL-578 has demonstrated single-agent activity in preclinical cancer models with high levels of replication stress.

On December 4, 2020 Angiocrine Bioscience Inc., a clinical-stage biopharmaceutical company reported that they have been selected by the American Society of Hematology (ASH) (Free ASH Whitepaper) for an oral presentation on the preliminary results of a Phase 1b/2 study of AB-205 to prevent or reduce severe organ toxicities associated with high-dose therapy followed by autologous hematopoietic cell transplantation used with curative intent in patients with aggressive systemic lymphoma (Press release, Angiocrine Bioscience, DEC 4, 2020, View Source [SID1234572187]).

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"Our investigators and Angiocrine are honored to be selected by ASH (Free ASH Whitepaper) to present at its annual meeting this December," commented Paul Finnegan, MD, Angiocrine CEO. "We look forward to Dr. Michael Scordo’s presentation of AB-205’s efficacy and safety results from our Phase 1b/2 study as well as preparing for the upcoming Phase 3 registration study for this indication."

Session Name: 723. Clinical Allogeneic and Autologous Transplantation: Late Complications and Approaches to Disease Recurrence I
Session Date: Saturday, December 5, 2020
Session Time: 7:30 AM – 9:00 AM ET
Presentation Time: 7:45 AM ET

About Severe Regimen-Related Toxicities
High-dose therapy and autologous hematopoietic cell transplantation is considered a standard-of-care method to cure aggressive systemic lymphoma. High dose therapy effectively eradicates cancer cells but also damages healthy tissue, which can lead to severe toxicities. Most affected is the lining of the oral-gastrointestinal (GI) tract. The oral GI tract renews its mucosal lining every 3 to 7 days. Because of the collateral damage from high dose chemotherapy, the oral GI tract loses its ability to renew its lining, leading to inflammation (mucositis) and breakdown, causing nausea, vomiting and diarrhea that are refractory to available medications and require prolonged hospitalization. Severe oral GI toxicities can occur as frequently as 50% and cause profound misery to patients. The rates and severity increase with age and, thus, many older patients are turned away from the curative high dose therapy due to the risks of severe toxicities.

About AB-205
AB-205 represents a new and unique approach to repairing damaged tissue through advanced cell-and-gene therapy. AB-205 consists of allogeneic (off-the shelf) ‘universal’ E-CEL (human engineered cord endothelial) cells. Intravenous AB-205 is given after chemotherapy/radiation (high-dose therapy) conditioning and on the same day as autologous transplant. AB-205’s immediate action repairs damaged tissue and thereby prevents (reduces) the extent of breakdown of tissues, which is the root cause of severe toxicities experienced by patients. Reducing or preventing severe toxicities means better quality of life and shorter stay in the hospital—i.e., savings to the healthcare system. AB-205 was recently granted both the Regenerative Medicine Advanced Therapy (RMAT) Designation and Orphan Drug Designation (ODD) by the U.S. Food and Drug Administration (FDA). Angiocrine is actively planning to advance AB-205 into a multi-center single registration Phase 3 trial based on the results of the Phase 1b/2 study.

On December 4, 2020 Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) reported that data related to TAVALISSE (fostamatinib disodium hexahydrate) tablets will be presented in two poster presentations at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition to be held virtually December 5-8, 2020 (Press release, Rigel, DEC 4, 2020, View Source;exposition-301186305.html [SID1234572185]). The poster presentations will be made available on the event’s website at View Source on Saturday, December 5 at 7:30am PT.

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Rigel will present an analysis of long-term safety data on fostamatinib in more than 3,500 patients at various dosing regimens with immune thrombocytopenia (ITP) or rheumatoid arthritis (RA). No new safety signals nor cumulative toxicity were observed with up to 62 months (5.2 years) of continuous treatment in ITP patients and up to 81 months (6.8 years) of continuous treatment in RA patients.

An overview of Rigel’s ongoing Phase 3 clinical trial of fostamatinib in warm autoimmune hemolytic anemia (wAIHA) will also be presented. This is a randomized, double-blind, placebo-controlled study of approximately 90 patients with primary or secondary wAIHA who have failed at least one prior treatment. This study is based on Rigel’s Phase 2, open-label, multi-center study for the treatment of wAIHA. Results of that study demonstrated that 44% (11/25) of patients had markedly improved hemoglobin (Hgb) levels and adverse events were consistent with those in the fostamatinib safety database.

Additionally, Rigel’s planned Phase 3 clinical trial to evaluate the efficacy and safety of fostamatinib in adult, hospitalized COVID-19 patients was featured in an ASH (Free ASH Whitepaper) abstract published in the November 26, 2020, issue of Blood. This is a multi-center, double-blind, placebo-controlled, adaptive design study with a primary endpoint that measures the proportion of subjects who progress to severe/critical disease within 29 days.

Fostamatinib is commercially available in the U.S. under the brand name TAVALISSE (fostamatinib disodium hexahydrate) tablets, which is the first and only spleen tyrosine kinase (SYK) inhibitor indicated for the treatment of thrombocytopenia in adult patients with chronic ITP who have had an insufficient response to a previous treatment. The FDA has granted TAVALISSE Orphan Drug designation for the treatment of patients with warm AIHA.

Poster Presentations
Abstract #838
Long-Term Safety Profile of the Oral Spleen Tyrosine Kinase Inhibitor Fostamatinib in Immune Thrombocytopenia (ITP) and Other Diseases
Presenter: Aaron Sheppard, PhD
Session Name: 311. Disorders of Platelet Number or Function: Poster I
Date & Time: Saturday, December 5, 2020: 7:00 AM-3:30 PM PT

Abstract #752
Fostamatinib for the Treatment of Warm Antibody Autoimmune Hemolytic Anemia (wAIHA): A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Global Study
Presenting Author: Nichola Cooper, MD
Session Name: 101. Red Cells and Erythropoiesis, Structure and Function, Metabolism, and Survival, Excluding Iron: Poster I
Date & Time: Saturday, December 5, 2020: 7:00 AM-3:30 PM PT

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 include fatigue, 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. In addition to fostamatinib, 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. 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. To date, there are no disease-targeted therapies approved for AIHA, despite the unmet medical need that exists for these patients.

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.