On December 13, 2021 TG Therapeutics, Inc. (NASDAQ: TGTX), reported four data presentations, including three oral presentations and one poster presentation, evaluating the combination of ublituximab, the Company’s investigational anti-CD20 monoclonal antibody and UKONIQ (umbralisib), the Company’s inhibitor of PI3K-delta and CKI-epsilon, (U2), as well as U2-based triple combination therapies, including U2 plus TG’s investigational BTK inhibitor TG-1701 (Press release, TG Therapeutics, DEC 13, 2021, View Source [SID1234596946]). Data presentations occurred this past weekend during the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting and exposition. Presentation highlights are included below.

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Michael S. Weiss, Chairman and Chief Executive Officer of TG Therapeutics stated, "We are excited to have showcased four presentations this past weekend, including three oral presentations, during the live ASH (Free ASH Whitepaper) annual meeting. It was also gratifying to learn that two of our oral presentations, U2 in relapsed or refractory MZL and U2 as an add-on to Ibrutinib to create a time-limited therapy, were chosen for highlights of ASH (Free ASH Whitepaper). We believe these presentations further demonstrate the potential for U2 to enhance patient care and complement current standard of care for patients with B-cell malignancies."

PRESENTATION HIGHLIGHTS

Oral Presentation Title: The Combination of Umbralisib Plus Ublituximab Is Active in Patients with Relapsed or Refractory Marginal Zone Lymphoma (MZL): Results from the Phase 2 Global Unity-NHL Trial

A total of 72 relapsed/refractory (R/R) marginal zone lymphoma (MZL) patients were enrolled in the ublituximab plus umbralisib (U2) cohort of the UNITY-NHL.
Patients had a median of 2 prior lines of therapy (range 1 – 9), with 25% refractory to their immediate prior therapy
Overall Response Rate (ORR) by independent review committee (IRC) was 70%, with 21% complete response (CR) rate (n=71),
Median duration of response (DOR) was not reached at a median follow up of 20 months.
Grade 3/4 AEs of clinical interest included diarrhea (13%), neutropenia (18%), ALT/AST increased (15%) and non-infectious colitis (2.8%).
Oral Presentation Title: Efficacy and Safety of Umbralisib, Ublituximab (U2), and U2 Plus Bendamustine in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

A total of 226 patients were treated within the DLBCL cohort of the UNITY-NHL trial. 30 patients received umbralisib monotherapy, 66 patients received ublituximab plus umbralisib or U2, and 130 patients received U2 plus bendamustine.
IRC assessed response rates:
43% ORR and 17% CR for U2 plus bendamustine triple combination (n=130)
32% ORR and 11% CR for U2 double combination (n=66)
13% ORR and 3% CR for umbralisib monotherapy (n=30)
IRC assessed median duration of response (DOR) was 3 months for umbralisib monotherapy, 28 months for U2 combination, and 8 months for U2 plus bendamustine
Both U2 and U2 + bendamustine demonstrated a manageable safety profile. Grade 3/4 AEs of special interest occurring in the U2 group (n=66) included ALT/AST increased (12%), non-infectious colitis (2%), diarrhea (2%), neutropenia (11%) and pneumonitis (2%). Grade 3/4 AEs of special interest occurring in the U2 plus bendamustine group (n=130) included ALT/AST increased (5%), non-infectious colitis (2%), diarrhea (7%), neutropenia (27%), pneumonitis (1%) and rash (2%).
Oral Presentation Title: A Phase 2 Study Evaluating the Addition of Ublituximab and Umbralisib (U2) to Ibrutinib in Patients with Chronic Lymphocytic Leukemia (CLL): A Minimal Residual Disease (MRD)-Driven, Time-Limited Approach-Limited Approach

This study utilized an "add-on" approach, where the combination of umbralisib and ublituximab (U2) was added to therapy in patients who were on ibrutinib for greater than 6 months and had detectable minimum residual disease (MRD)
Patients who achieve undetectable MRD (uMRD) or those who completed 24 cycles of therapy with detectable MRD stop all therapy and enter a period of treatment-free observation (TFO). Patients with clinical progression during TFO are eligible for re-treatment with the U2 + ibrutinib combination.
28 patients with chronic lymphocytic leukemia (CLL) were enrolled, with 27 evaluable for efficacy. Patients were on ibrutinib for a median of 21 months (range 7-67) prior to study entry.
77% of evaluable patients achieved uMRD, with a median time to first uMRD of 7.4 months
Grade 3/4 AEs included diarrhea (4%), hypertension (7%), ALT/AST increased (4%) and COVID-19 (4%).
Poster Presentation Title: The Selective Bruton Tyrosine Kinase (BTK) Inhibitor TG-1701 As Monotherapy and in Combination with Ublituximab and Umbralisib (U2) in Patients with B-Cell Malignancies

A total of 135 patients with R/R CLL or B-cell lymphoma were included in this presentation, with patients receiving 200 mg of TG-1701 in a dose-expansion cohort (n=61), 300 mg of TG-1701 in a CLL dose-expansion cohort (n=20), TG-1701 in combination with U2 in a dose escalation cohort (TG-1701 doses ranging from 100 – 300 mg once daily and umbralisib at either 600 mg or 800mg) (n=21), and a triple combination expansion cohort of 100mg of TG-1701 plus U2 (400 mg of umbralisib) (n=33).
Efficacy Overall Response Rate (ORR) and Complete Response (CR) Outcomes:
100% ORR observed in the CLL 300 mg QD TG-1701 monotherapy expansion cohort at a median follow up of 13.8 months (n=19)
95% ORR observed in the CLL 200 mg QD TG-1701 monotherapy expansion cohort at a median follow up of 20 months (n=20)
86% ORR, including 19% CR rate, observed in the 1701+U2 dose escalation cohort (using doses of 100 mg to 300 mg QD of TG-1701) at a median follow up of 20.2 months (n=21)
83% ORR, including 6% CR rate, observed in the 1701+U2 dose expansion cohort (using 100 mg QD of TG-1701 and 400 mg QD of umbralisib) at a median follow up of 2.7 months (n=18)
Grade 3/4 AEs occurring in patients treated with 200 mg QD of TG-1701 (n=61) and 300 mg QD of TG-1701 (n=20), respectively, included neutropenia (8%, 20%), ALT increased (3%, 5%), AST increased (2%, 5%) and anemia (5%, 0%). Grade 3/4 AEs occurring in patients treated with the triple combination in the U2 plus TG-1701 expansion cohort (100 mg QD TG-1701 plus 400 mg QD of umbralisib; n=19) and U2 plus TG-1701 escalation cohort (100 mg to 300 mg QD; n=21), respectively, included neutropenia (16%, 19%), ALT increased (5%, 19%), AST increased (5%, 14%).
At the time of data cut-off, no patients had discontinued treatment due to a treatment-related adverse event across all cohorts.
The above referenced presentations are now available on the Publications page of the Company’s corporate website at View Source

On December 13, 2021 Sierra Oncology, Inc. (NASDAQ: SRRA), a late-stage biopharmaceutical company on a mission to deliver targeted therapies that treat rare forms of cancer, reported data from new retrospective analyses of the Phase 3 SIMPLIFY studies demonstrate baseline ferritin differentially predicts Week 24 Transfusion Independence Response for momelotinib and ruxolitinib in patients with myelofibrosis (Press release, Sierra Oncology, DEC 13, 2021, View Source [SID1234596973]). The data were presented at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting being held virtually and in Atlanta, GA December 11-14, 2021.

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Baseline Serum Ferritin Differentially Predicts W24 Transfusion Independence Response for Momelotinib and Ruxolitinib in Patients with Myelofibrosis

Myelofibrosis is characterized by the presentation of constitutional symptoms, splenomegaly and anemia, with the degree of anemia and transfusion dependence being among the most important predictors of overall survival. Dr. Stephen Oh, MD, PhD, Washington University School of Medicine in St. Louis and Siteman Cancer Center, noted how the analyses identified pre-treatment serum ferritin level as the most predictive biomarker for the treatment effect of momelotinib versus ruxolitinib on Week 24 Transfusion Independence Response (TI-R) in the SIMPLIFY-1 (JAK inhibitor-naïve) and SIMPLIFY-2 (JAK-inhibitor experienced) studies.

Key results for SIMPLIFY-1 include:

Ruxolitinib was associated with a significantly greater increase in ferritin levels over time compared with momelotinib, irrespective of baseline ferritin, highlighting the differential treatment impact on serum ferritin between the two agents
Baseline hemoglobin (Hgb), an indicator of anemic status, differentially predicted Week 24 TI-R in patients randomized to momelotinib or ruxolitinib
Baseline ferritin also differentially predicted Week 24 TI-R in patients randomized to momelotinib or ruxolitinib
For patients with baseline ferritin between 90-650 ng/mL, momelotinib-treated patients had a higher Week 24 TI-R rate than ruxolitinib-treated patients [72% vs. 38%, OR 4.21 (95% CI: 2.24, 7.89); p=0.0439]
In patients with baseline Hgb <12 g/dL, baseline ferritin levels provided additional, differential predictive value for Week 24 TI-R
The differential treatment effect between momelotinib and ruxolitinib was highest for anemic patients with baseline ferritin between 90-650 ng/ml
No correlation was observed between baseline ferritin and Week 24 splenic or symptom response rates
Findings from SIMPLIFY-1 were independently confirmed in the JAK inhibitor experienced setting of the SIMPLIFY-2 study, where Hgb and ferritin each differentially predicted Week 24 TI-R in patients randomized to momelotinib or best available therapy (BAT; 88.5% ruxolitinib), and baseline ferritin predicted additional, differential predictive value for Week 24 TI-R in patients with Hgb <12 g/dL. For patients with baseline ferritin between 90-650 ng/mL, momelotinib-treated patients had higher Week 24 TI-R than those treated with BAT [53% vs 22%, OR 2.27 (95% CI: 1.01,12.77); p=0.03099].

These data suggest that ferritin may be useful in treatment decision making in myelofibrosis, especially in patients with anemia and ferritin 90-650 ng/mL, in which momelotinib demonstrates a greater TI effect than ruxolitinib. Future evaluation may be made in forthcoming clinical trials to further examine the correlation between ferritin and TI response.

About Momelotinib

Momelotinib is a selective and orally bioavailable JAK1, JAK2 and ACVR1/ALK2 inhibitor currently under investigation for the treatment of myelofibrosis. Myelofibrosis results from dysregulated JAK-STAT signaling and is characterized by constitutional symptoms, splenomegaly (enlarged spleen) and progressive anemia.

Sierra Oncology is currently awaiting topline results of the MOMENTUM clinical trial, a global, randomized, double-blind Phase 3 study evaluating momelotinib for the treatment of symptomatic and anemic myelofibrosis patients. Top-line data are anticipated by February 2022. Assuming positive data, the company plans to file a New Drug Application with the US Food & Drug Administration (FDA) in the second quarter of 2022. The FDA has granted Fast Track designation for momelotinib.

On December 13, 2021 Cellular Biomedicine Group Inc. (CBMG or the "Company"), a biopharmaceutical company developing innovative cellular immunotherapies for the treatment of cancer, reported that the Food and Drug Administration (FDA) granted clearance of the Investigational New Drug (IND) application to proceed with the Phase 1b clinical development of its chimeric antigen receptor (CAR) T-cell therapy targeting CD19 and CD20 (C-CAR039) (Press release, Cellular Biomedicine Group, DEC 13, 2021, View Source [SID1234596995]). C-CAR039 is a novel autologous bi-specific CAR-T therapy targeting both CD19 and CD20 antigens in the treatment of patients with relapsed or refractory non-Hodgkin lymphoma (r/r B-cell NHL).

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"This is fantastic news for us as we believe we may potentially have best-in-class therapeutics for patients with poor prognosis. The largest subtype of NHL is DLBCL, and those refractory patients whose treatment has failed have limited options. We look forward to initiating the C-CAR039 trial soon," said Tony (Bizuo) Liu, Chairman and CEO. "The FDA’s C-CAR039 IND application clearance is a significant milestone for CBMG. We are fond of our manufacturing, quality control, and clinical development teams for their dedication to our mission of ‘Saving Lives and Revitalizing Lives’ and bringing to market innovative targeted therapies to address cancers."

Yihong Yao, PhD, Chief Scientific Officer of CBMG, commented, "We are excited about the potential of C-CAR039 as a best-in-class treatment in r/r B-NHL. C-CAR039 clearly showed potential superior efficacy and favorable safety results for patients with r/r B-cell NHL. Our C-CAR039 trial is a testament of the teams’ translational medicine capability. We look forward to bringing more potentially promising development to clinical trials."

About C-CAR039
Early clinical results of C-CAR039 from an investigator-initiated trial (IIT) conducted across multiple sites in China demonstrate exciting efficacy and favorable safety data of C-CAR039 in r/r B-cell NHL. As of April 20, 2021, a total of 34 patients received C-CAR039 cell therapies, with 28 patients evaluable for safety analyses and 27 patients evaluable for efficacy analyses. Patients’ median age was 55.5 years, and 75% had cancer of Ann Arbor stage III/IV. Patients had a median of three prior lines of therapy. Bridging therapy had been given to 17.9% of patients. The best overall response rate (ORR) was reported to be 92.6%, with a complete response rate (CRR) of 85.2%. Patients had a median time to response of 1.0 month, and at a median follow-up of 7 months, 74.1% of patients continued to be in complete remission. The 6-month estimated progression-free survival rate was 83.2% (95% CI, 69.1%-100.0%). Cytokine release syndrome (CRS) occurred in 96% of patients. 92% of CRS was of grade 1/2 and only 1 patient had grade 3 CSR. Immune effector cell-associated neurotoxicity syndrome occurred at grade 1 in 2 patients and no ≥grade 2 neurologic events reported in the study. CBMG will continue to evaluate patients with longer follow-up (ClinicalTrials.gov Identifiers: NCT04317885, NCT04655677, NCT04696432, NCT04693676).

Separately, in June 2021, the FDA Office of Orphan Products Development granted CBMG an Orphan Drug Designation to C-CAR039 for the treatment of Follicular Lymphoma, an indolent form of non-Hodgkin lymphoma.

About CBMG
Cellular Biomedicine Group Inc. (CBMG) is a wholly owned subsidiary of CBMG Holdings. CBMG Holdings ("Holdings") develops proprietary cell therapies for the treatment of cancer and degenerative diseases. CBMG operates a state-of-the-art facility in Rockville, Maryland with five GMP rooms in order to augment its global research and development capabilities and to support clinical development of multiple cell therapy platform technologies in the United States. Holdings conducts immuno-oncology and stem cell clinical trials in China using products from its integrated GMP laboratory. Holdings’ GMP facilities in China, consisting of twelve independent cell production lines, are designed and managed according to both China and U.S. GMP standards. Holdings currently conducts ongoing studies in China, for CAR-T therapies targeting blood cancers, including C-CAR039, an anti-CD19, CD20 BiCAR treatment for non-Hodgkin lymphoma (NHL) and CAR088, an anti-BCMA treatment for Multiple Myeloma, in addition to T cell receptor (TCR-T) and tumor-infiltrating lymphocytes (TIL) therapies targeting solid tumors. Holdings has completed patient treatment in a Phase II trial for AlloJoin, its "Off-the-Shelf" allogenic haMPC therapy for the treatment of Knee Osteoarthritis (KOA), and a Phase II trial for ReJoin autologous haMPC therapy for the treatment of KOA.

On December 13, 2021 Arbutus Biopharma Corporation (Nasdaq: ABUS), a clinical-stage biopharmaceutical company dedicated to developing a cure for people with chronic hepatitis B virus (HBV) infection, and Qilu Pharmaceutical, one of the leading pharmaceutical companies in China, reported that the companies have entered into an exclusive licensing agreement and strategic partnership for the development and commercialization of AB-729 for the treatment or prevention of hepatitis B in mainland China, Hong Kong, Macau and Taiwan (Press release, Arbutus Biopharma, DEC 13, 2021, View Source [SID1234596909]).

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AB-729 is Arbutus’s lead RNA interference (RNAi) therapeutic that is currently in multiple Phase 2a proof-of-concept clinical trials designed to evaluate it in combination with other approved or investigational agents.

William Collier, President and Chief Executive Officer of Arbutus Biopharma, commented, "Qilu is an ideal partner for our AB-729 RNAi therapeutic given their extensive development, regulatory and commercialization capabilities in China. We are now positioned to bring AB-729 to the largest HBV patient population in need of a cure and to tap into one of the largest and most promising healthcare markets worldwide. We are committed to working with Qilu in this partnership which further validates the potential of AB-729 to address the unmet medical need in HBV."

Qilu Pharmaceutical Chief Executive Officer, Ms. Yan Li commented, "The HBV patient population is significant in China. Based on clinical data achieved to-date, we believe in the potential of AB-729 to be a safe and effective treatment option in treating HBV. We look forward to collaborating with Arbutus to maximize the potential clinical value that AB-729 can bring to and benefit the millions of underserved HBV patients in China."

Under the terms of the agreement, Arbutus will receive a $40 million upfront payment and will be entitled to additional payments of up to $245 million upon reaching certain development, regulatory and sales milestones. The above amounts are net of withholding taxes. Qilu will be responsible for funding all development and commercialization activities for mainland China, Hong Kong, Macau and Taiwan. Arbutus is also entitled to receive double-digit tiered royalties up to the low twenties percent on annual net sales. In addition, Qilu will make a $15 million equity investment in Arbutus common shares at a price of $4.19 per share, a 15% premium of Arbutus’ previous 30-day average closing stock price calculated from December 10, 2021.

The common shares to be sold in the private placement have been offered only to certain institutional and/or accredited investors in reliance upon an exemption from the registration requirements of the Securities Act of 1933, as amended (the "Securities Act"). The common shares have not been registered under the Securities Act or any state or other securities laws and may not be offered or sold in the United States absent registration or an applicable exemption from registration requirements of the Securities Act and applicable state securities laws. The Securities and Exchange Commission has not passed upon the merits of or given its approval to the common shares, the terms of the private placement or the accuracy or completeness of any private placement materials. The common shares sold in the private placement are subject to legal restrictions on transfer.

This press release shall not constitute an offer to sell or a solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification or otherwise under the securities laws of any such state or jurisdiction.

About AB-729

AB-729 is an RNA interference (RNAi) therapeutic specifically designed to reduce all HBV viral proteins and antigens, including hepatitis B surface antigen, which is thought to be a key prerequisite to enable reawakening of a patient’s immune system to respond to the virus. AB-729 targets hepatocytes using Arbutus’ novel covalently conjugated N-acetylgalactosamine (GalNAc) delivery technology that enables subcutaneous delivery. Clinical data generated thus far has shown single- and multi-doses of AB-729 to be generally safe and well-tolerated while providing meaningful reductions in hepatitis B surface antigen and hepatitis B DNA.

About HBV

Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV). HBV can cause chronic infection which leads to a higher risk of death from cirrhosis and liver cancer. Chronic HBV infection represents a significant unmet medical need. The World Health Organization estimates that over 250 million people worldwide suffer from chronic HBV infection, while other estimates indicate that approximately 2 million people in the United States suffer from chronic HBV infection. Approximately 900,000 people die every year from complications related to chronic HBV infection despite the availability of effective vaccines and current treatment options.

On December 13, 2021 Infinity Pharmaceuticals, Inc. (NASDAQ: INFI), a clinical-stage biotechnology company developing eganelisib, a potentially first-in-class, oral, immuno-oncology macrophage reprogramming therapeutic that selectively inhibits phosphoinositide-3-kinase gamma (PI3K-gamma), reported that it will be highlighted during a "Best Ideas" virtual fireside chat with B. Riley Biotech research analyst Kalpit Patel on Tuesday, December 14th at 2:30 pm ET. The fireside chat will feature an interactive discussion with Key Opinion Leader (KOL) and MARIO-3 TNBC Investigator, Hatem Soliman, MD (Moffitt Cancer Center), Infinity’s CEO, Adelene Perkins, and Infinity’s CMO, Dr. Robert Ilaria (Press release, Infinity Pharmaceuticals, DEC 13, 2021, View Source [SID1234596926]).

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To register for the webinar please contact a B.Riley sales representative or Kalpit Patel, Pharm.D., 646-885-5447, [email protected].

Hatem Soliman, MD is one of the leading breast cancer physicians in the country and an investigator on the MARIO-3 study. Dr. Soliman serves as the Medical Director of the Clinical Trials Office at the Moffitt Cancer Center, with extensive experience as a clinical investigator conducting both translational research in breast cancer immunotherapy and leading numerous clinical trials as principal investigator since joining the faculty at Moffitt in 2008. He also serves as the Course Director for the fellowship clinical research rotation, medical director of the phase 1 program, chair of Moffitt’s clinical research leadership council, chair of clinical research feasibility committee, and principal investigator for Moffitt’s CPDM CCSG application, which was recently rated as outstanding and awarded funding for an additional five years.

Dr Soliman received his BS in Genetics from the University of Georgia Athens in 1996 and then went on to receive his medical degree from the Medical College of Georgia in 2002. His residency and fellowship training in oncology/hematology was completed through the University of South Florida/Moffitt Cancer Center program in 2008. During fellowship, he authored investigator initiated early phase trials with mentorship from Dr. Daniel Sullivan, former ACD and EVP of Moffitt, in collaboration with the NCI CTEP RAID program investigators Drs. Jaime Zwiebel and Howard Streicher. Upon graduation, Dr. Soliman was offered an assistant member position at Moffitt as a clinical investigator to continue early drug development and translational research activities.