On June 12, 2020 TG Therapeutics, Inc. (NASDAQ: TGTX), reported data presentations at the 25th European Hematology Association (EHA) (Free EHA Whitepaper) annual congress including data from a Phase 1 study evaluating TG-1701, the Company’s once daily, selective, BTK inhibitor, as monotherapy and in combination with umbralisib and ublituximab (U2) in relapsed/refractory chronic lymphocytic leukemia (CLL) and lymphoma, as well as long term data from a Phase 1/1b study evaluating the combination of umbralisib and ibrutinib in relapsed/refractory CLL and mantle cell lymphoma (MCL) (Press release, TG Therapeutics, JUN 12, 2020, View Source [SID1234561032]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer stated, "We have long been excited about the potential for dual BCR blockade by targeting both PI3K-delta and BTK in the treatment of hematologic malignancies, and these data presentations offer insight into the therapeutic potential for this dual targeted approach. We are extremely pleased to see that TG-1701 continues to exhibit an encouraging safety and efficacy profile, both as a monotherapy and in our proprietary triplet combination with U2, with additional patients now treated and with longer follow-up. We now have patients on TG-1701 for upwards of 1.5 years, with no patients having discontinued therapy due to toxicity and responses deepening over time. We were also excited to see long-term data for the all-oral combination of umbralisib and ibrutinib, which similarly demonstrated continued improvement in overall response rates, and importantly identified no long-term safety signals at over 3.5 years of follow-up, underscoring the potential combinability of umbralisib with BTK therapy." Mr. Weiss continued, "In striving towards our goal of developing novel combination treatments for patients with unmet medical needs, we are highly encouraged by the data presented today and look forward to continuing dose escalation for our proprietary triple combination of ublituximab, umbralisib and TG-1701."

Details of the data presentations are included below.

Presentation Title: Safety and activity of the once daily selective bruton tyrosine kinase (BTK) inhibitor TG-1701 in patients with chronic lymphocytic leukemia (CLL) and lymphoma

This presentation includes interim data from a Phase 1 parallel dose-escalation study of TG-1701 monotherapy and TG-1701 in combination with U2 in 82 patients with relapsed/refractory B-cell malignancies. Sixty-nine patients were treated with single agent TG-1701, of which 25 patients were treated in the monotherapy dose escalation portion of the study and received TG-1701 at doses that ranged from 100mg to 400mg once daily, and 44 patients were treated with 200mg of TG-1701 in the monotherapy dose expansion cohort. An additional 13 patients were treated in the TG-1701 plus U2 dose escalation portion of the study.

Safety and efficacy highlights include:

TG-1701 monotherapy exhibited an encouraging preliminary safety profile across all dose levels evaluated with only 3% (2/69) of patients having a dose reduction due to treatment-related adverse events (AEs), with no treatment discontinuations due to AEs in the monotherapy cohorts
In the monotherapy dose escalation cohort (n=25), TG-1701 produced partial responses at all dose levels evaluated (100mg to 400mg once daily) in CLL, MCL, Waldenström’s macroglobulinemia (WM), and small lymphocytic lymphoma (SLL)
In the monotherapy dose expansion cohort in which TG-1701 was administered at 200mg, 25 patients were evaluable for efficacy with a 92% overall response rate (ORR) observed in CLL patients (n=12), a 33% ORR in MCL patients (n=6), and a 86% ORR in WM patients (n=7)
The combination of TG-1701 plus U2 has been well tolerated and demonstrated encouraging clinical activity with a 77% ORR across all disease types (n=13), including complete responses in three patients; dose escalation continues
Presentation Title: Long term results of a Phase I/Ib study of ibrutinib in combination with umbralisib in patients with relapsed/refractory CLL or MCL

This presentation includes updated long term data from a Phase 1/1b study of patients with relapsed or refractory CLL or MCL treated with umbralisib in combination with ibrutinib. Data from this trial were previously published in Lancet Haematology in December 2018 (Davids et.al.). As of the updated data cutoff, 42 patients were evaluable for safety and efficacy (21 CLL patients and 21 MCL patients).

Safety and efficacy highlights include:

With long term follow up (median follow-up of 43.5 months (range 8.4-61), there were no cumulative or recurrent late onset toxicities observed
In relapsed/refractory CLL, the overall response rate was 95% including a 29% complete response (CR) rate, and the 4-year Progression-free Survival (PFS) and Overall Survival (OS) were 78% and 90%, respectively
In relapsed/refractory MCL, the ORR was 71% with a 24% CR rate, and median PFS and OS were 10.8 and 30.7 months, respectively
The data presented is available on the Publications page, located within the Pipeline section, of the Company’s website at www.tgtherapeutics.com/publications.cfm.

On June 12, 2020 Imago BioSciences reported the presentation of data at the 2020 Virtual European Hematology Association (EHA) (Free EHA Whitepaper) meeting relating to the clinical trial of bomedemstat (IMG-7289) for the treatment of advanced myelofibrosis (Press release, Imago BioSciences, JUN 12, 2020, View Source [SID1234561031]). The abstract published online in May included an analysis of data from 34 patients. The presentation today as a poster reflects a more extensive analysis of a larger patient population based on a later data cutoff.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The poster enumerates spleen volume reductions and improvements in Total Symptom Scores in a majority of patients. Additionally, there were improvements in hemoglobin with patients transitioning from transfusion-dependence to transfusion-independence and bone marrow fibrosis improvements," said Kristen Petitt, MD, Assistant Professor of Medicine at the University of Michigan, Rogel Cancer Center, in Ann Arbor. "In this ongoing study, the preliminary data indicate that bomedemstat has significant clinical activity as monotherapy in a myelofibrosis patient population with advanced disease and no therapeutic alternatives."

Data Highlights

Bomedemstat (IMG-7289) monotherapy in intermediate-2 /high-risk patients with myelofibrosis who have become intolerant or resistant to a JAK inhibitor

Of evaluable patients at 24 weeks:
83% had spleen volume reductions
86% demonstrated reductions in Total Symptom Scores (TSS)
70% of patients had stable or improved hemoglobin
71% of patients had a stable or improved BM fibrosis score
>90% of patients with elevated circulating inflammatory cytokines showed significant reductions
Safety

Bomedemstat (IMG-7289) in patients with myelofibrosis was generally well tolerated. No dose-limiting toxicities were observed, and a maximum tolerated dose was not identified.

There were 723 adverse events (AEs) reported, of which 215 were attributed to bomedemstat. Only four SAEs — painful splenomegaly, heart failure, headache, rectal bleeding (all Grade 3) — were deemed by the Investigator to be related to bomedemstat. There were no Grade 5 events related to bomedemstat.

The most common treatment-emergent AEs deemed related to bomedemstat was dysgeusia (33%).

For further details, please see the 2020 EHA (Free EHA Whitepaper) abstract and poster on Imago’s website at www.imagobio.com.

Poster Presentation

TITLE: A PHASE 2 STUDY OF BOMEDEMSTAT (IMG-7289), A LYSINE-SPECIFIC DEMETHYLASE-1 (LSD1) INHIBITOR, FOR THE TREATMENT OF MYELOFIBROSIS (MF)

Session: Myeloproliferative Neoplasms—Clinical

Date and Time: June 12, 2020, 8:30 AM CEST/2:30 AM EDT

About Bomedemstat (IMG-7289)

Bomedemstat is being evaluated in an open-label Phase 2 clinical trial (www.myelofibrosisclinicalstudy.com) for the treatment of myelofibrosis (MF), a bone marrow cancer that interferes with the production of blood cells. The endpoints include spleen volume reduction and symptom improvement at 12 and 24 weeks of treatment. Bomedemstat is used as monotherapy in patients who are resistant to, intolerant of, or ineligible for ruxolitinib.

Bomedemstat is a small molecule developed by Imago BioSciences that inhibits lysine-specific demethylase 1 (LSD1 or KDM1A), an enzyme shown to be vital in cancer stem/progenitor cells, particularly neoplastic bone marrow cells. In non-clinical studies, IMG-7289 demonstrated robust in vivo anti-tumor efficacy across a range of myeloid malignancies as a single agent and in combination with other chemotherapeutic agents. Bomedemstat (IMG-7289) is an investigational agent currently being evaluated in ongoing clinical trials (ClinicalTrials.gov Identifier: NCT03136185 and NCT04254978). Bomedemstat has FDA Orphan Drug and Fast Track Designation for the treatment of myelofibrosis, essential thrombocythemia and acute myeloid leukemia.

On June 12, 2020 Agios Pharmaceuticals, Inc. (NASDAQ: AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, and Royalty Pharma reported that Agios has sold its tiered, sales-based royalty rights on worldwide net sales of Bristol Myers Squibb’s IDHIFA (enasidenib), as well as its rights to receive up to $55 million in outstanding regulatory milestone payments from Bristol Myers Squibb, to Royalty Pharma for $255 million (Press release, Agios Pharmaceuticals, JUN 12, 2020, View Source [SID1234561030]). Agios will continue to co-promote IDHIFA and receive reimbursement from Bristol Myers Squibb for this co-promotion under its 2010 collaboration agreement with Celgene, a wholly owned subsidiary of Bristol Myers Squibb. Agios also retains the right to receive a $25 million payment upon achievement of a specified ex-U.S. commercial milestone event. IDHIFA is an oral, targeted therapy approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"It is an exciting time at Agios with multiple ongoing mid- and late-stage trials in each of our core therapeutic focus areas that we believe have the potential to make a meaningful difference in patients’ lives. This non-dilutive funding provides us with additional financial flexibility as we continue to invest in advancing our robust clinical pipeline, including mitapivat across three rare disease indications and our IDH inhibitors in solid tumors and novel combination approaches for AML," said Jackie Fouse, Ph.D., chief executive officer of Agios. "Royalty Pharma, a pioneer in this space, is an industry leader in identifying promising late-stage and commercial therapies, and we are pleased with their recognition of IDH inhibition as an important therapeutic approach for hematologic malignancies."

"IDHIFA is an innovative, targeted treatment that has benefited numerous AML patients who may otherwise have had few other treatment options," said Pablo Legorreta, founder and chief executive officer of Royalty Pharma. "We are delighted to partner with Agios, a biotechnology company that stands out for its strong scientific foundation and a track record of successful development of multiple innovative targeted therapies. The proceeds that Agios will receive today will help further their mission and fund their exciting pipeline that will drive the next phase of the company’s growth."

Cowen served as financing advisor to Agios and Wilmer Hale served as legal advisor to Agios. Goodwin Procter LLP, Dechert LLP and Maiwald Patentanwalts- und Rechtsanwaltsgesellschaft mbH acted as legal advisors to Royalty Pharma on the transaction.

About the Agios/Celgene IDH Program
In 2010, Agios and Celgene Corporation, now a wholly owned subsidiary of Bristol Myers Squibb, entered into a collaboration agreement focused on cancer metabolism. Under the terms of the agreement, Celgene has worldwide development and commercialization rights for IDHIFA (enasidenib). Celgene and Agios are currently co-commercializing IDHIFA in the U.S., and Agios continues to conduct certain clinical development activities within the IDHIFA development program. Agios is eligible to receive a $25 million payment upon achievement of a specified ex-U.S. commercial milestone event, as well as reimbursement for costs incurred for its co-commercialization efforts and development activities.

On June 12, 2020 Sierra Oncology, Inc. (NASDAQ: SRRA), a late-stage drug development company focused on the registration and commercialization of momelotinib, a JAK1, JAK2 & ACVR1 inhibitor with a potentially differentiated therapeutic profile for the treatment of myelofibrosis, reported that Long-Term Safety and Dose Intensity data for momelotinib are being presented today in two posters at the 25th European Hematology Association (EHA) (Free EHA Whitepaper) Virtual Congress (Press release, Sierra Oncology, JUN 12, 2020, View Source [SID1234561029]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

More than 820 patients with myelofibrosis have received momelotinib during its development, including a number of patients who remain on treatment since the start of the original Phase 2 studies initiated a decade ago. One of these patients will reach a major milestone this week, having received momelotinib therapy for 10 years, highlighting the relevance of the long-term dosing and safety data for momelotinib being presented this week at EHA (Free EHA Whitepaper). The data presented at EHA (Free EHA Whitepaper) draw from more than 550 patients across the two previously conducted SIMPLIFY Phase 3 studies and their subsequent ongoing extended treatment periods. More than 90 SIMPLIFY-1 and SIMPLIFY-2 patients continued to receive momelotinib for 3.5 years or longer.

"Consistent with prior data, and reflecting momelotinib’s differentiated pharmacological profile, our new long-term safety analyses continue to show a rapid and sustained increase in hemoglobin levels during momelotinib therapy, in contrast to the significant decrease in hemoglobin for patients receiving ruxolitinib. Patients treated with momelotinib also experienced significantly higher mean platelet counts compared to those receiving ruxolitinib. Importantly, patients who switched from ruxolitinib to momelotinib also achieved a sustained improvement in both hemoglobin and platelets," said Prof. Claire Harrison, Guy’s and St. Thomas’ NHS Foundation Trust, London, United Kingdom. "In addition to an absence of significant rates of high-grade hematological toxicities, long-term tolerability was favorable with no new safety signals or evidence of cumulative toxicity. Notably, this was achieved with most patients receiving full-dose momelotinib."

"Momelotinib’s safety profile and durable anemia benefits facilitated sustained dose intensity across the continuum of JAK inhibitor naïve and previously JAK inhibitor treated myelofibrosis patients. While the starting doses for ruxolitinib were often attenuated due to low platelets, further reductions in dose intensity were also commonly required for ruxolitinib. In contrast, momelotinib was initiated at full dose for all subjects enrolled to the SIMPLIFY studies and high dose intensity was maintained in the majority over extended durations," said Dr. Vikas Gupta, Princess Margaret Cancer Centre, Toronto, Canada. "The ability to safely dose momelotinib sustainably at high dose intensity likely facilitates its ability to durably control the cardinal features of myelofibrosis, namely anemia, constitutional symptoms, and splenomegaly. Furthermore, patients who switch from ruxolitinib to momelotinib saw an immediate and sustained improvement in dose intensity, suggesting a link to the corresponding improvements in hemoglobin and platelets noted by Prof. Harrison. These data suggest that momelotinib may be an optimal therapy in myelofibrosis patients, in particular those experiencing hematological toxicity and disease-related myelosuppression, which are significant unmet needs in this disease."

The SIMPLIFY-1 trial was conducted in JAKi-naïve myelofibrosis patients (n=432) randomized 1:1 to momelotinib or ruxolitinib for 24 weeks. The SIMPLIFY-2 trial was conducted in prior ruxolitinib-treated myelofibrosis patients with hematological toxicity (n=156) randomized 2:1 to momelotinib or best available therapy (consisting of ruxolitinib in 88% of patients) for 24 weeks. All patients were then subsequently allowed to receive momelotinib for an extended treatment period including those who did not receive momelotinib initially, as they were eligible to cross-over to momelotinib at the end of the 24-week randomized treatment period in both studies.

About the Posters:
Please visit www.sierraoncology.com to view Prof. Harrison and Dr. Gupta present the momelotinib Long-Term Safety and Dose Intensity posters. Both e-posters are available through the on-demand EHA (Free EHA Whitepaper) Virtual Congress platform at View Source

Title: Long term Safety of Momelotinib in JAKi Naïve and Previously JAKi Treated Intermediate/High Risk Myelofibrosis Patients
Lead Author: Prof. Claire Harrison, Guy’s and St. Thomas’ NHS Foundation Trust, London, United Kingdom
Session Title: Myeloproliferative neoplasms – Clinical
Poster No.: EP1113

Title: Momelotinib Dose-Intensity is Maintained in JAKi Naïve and Previously JAKi Treated Intermediate/High Risk Myelofibrosis Patients
Lead Author: Dr. Vikas Gupta, Princess Margaret Cancer Centre, Toronto, ON, Canada
Session Title: Myeloproliferative neoplasms – Clinical
Poster No.: EP1103

On June 12, 2020 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported updated data on one of its investigational CD20xCD3 T-cell engaging bispecific antibodies, glofitamab (formerly known as CD20-TCB), in people with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) (Press release, Hoffmann-La Roche, JUN 12, 2020, View Source [SID1234561027]). Updated results from the phase I dose-escalation NP30179 study [NCT03075696] of glofitamab, administered via intravenous infusion for a fixed-duration of up to 12 21-day cycles, showed durable complete responses (CRs) in heavily pre-treated patients who had received a median of three prior lines of therapy. These data feature in an oral presentation (abstract #S241) at the European Hematology Association (EHA) (Free EHA Whitepaper) 25th Annual Congress Virtual Edition, taking place from 11-14 June 2020.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Non-Hodgkin lymphomas such as diffuse large B-cell lymphoma may present considerable treatment challenges, especially cases involving multiple relapses," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. "We’re encouraged by these early results which support the potential of glofitamab for patients who have failed multiple prior lines of therapy and need new treatment options urgently."

Updated efficacy data from the ≥0.6mg and ≥10mg cohorts showed high response rates across NHL subtypes.

In the ≥0.6mg cohorts, the investigator-assessed CR rate was 30.9% (38/123) for patients with aggressive NHL and the investigator-assessed overall response rate (ORR) was 45.5% (56/123). For patients with indolent NHL, the investigator-assessed CR rate was 52.2% (12/23) and the investigator-assessed ORR was 65.2% (15/23).
In the ≥10mg cohorts, the investigator-assessed CR rate was 34.1% (29/85) for patients with aggressive NHL and the investigator-assessed ORR was 49.4% (42/85). For patients with indolent NHL, the investigator-assessed CR rate was 50.0% (9/18) and the investigator-assessed ORR was 66.7% (12/18).
CRs also appeared durable. Of the patients achieving a CR in the ≥0.6mg cohorts, 72.7% (24/33) with aggressive NHL and 81.8% (9/11) with indolent NHL maintained their CR by the data cut-off date (17 April 2020). Median duration of CR was not reached in either group after a median follow-up of 10.2 months.
The safety profile of glofitamab was consistent with its mechanism of action. Common adverse events (AEs) occurring in over 15% of participants in the ≥0.6mg cohorts (n=156) were cytokine release syndrome (CRS; n=88, 56.4%), neutropenia (n=48, 30.8%), pyrexia (n=47, 30.1%), anaemia (n=35, 22.4%) and thrombocytopenia (n=26, 16.7%). The majority of CRS events were low grade (Grade 1-2), were associated with the first cycle, and were manageable.

A robust clinical development programme for glofitamab is ongoing, investigating the molecule alone and in combination with other Roche and non-Roche molecules. Combination regimens include studies with Polivy (polatuzumab vedotin), Tecentriq (atezolizumab), MabThera/Rituxan (rituximab) and Gazyva/Gazyvaro (obinutuzumab) in NHL and other blood cancers, across a variety of settings and tumour types, including earlier treatment lines, to identify where glofitamab may be able to provide benefit over current treatment options.

About glofitamab
Glofitamab is an investigational CD20xCD3 T-cell engaging bispecific antibody designed to target CD20 on the surface of B-cells and CD3 on the surface of T-cells. This dual targeting activates and redirects a patient’s existing T-cells to engage and eliminate target B-cells by releasing cytotoxic proteins into the B-cells. Glofitamab is based on a novel structural format which we call ‘2:1’, which refers to the structure of the antibody. It is engineered to have two ‘Fab’ regions which bind to CD20, and one ‘Fab’ region which binds to CD3. A robust clinical development programme for glofitamab is ongoing, investigating the molecule as a monotherapy and in combination with other medicines, for the treatment of people with CD20-positive B-cell non-Hodgkin lymphomas, including diffuse large B-cell lymphoma and follicular lymphoma, and other blood cancers.

About the NP30179 study
The NP30179 study [NCT03075696] is a phase I/Ib, multicentre, open-label, dose-escalation study, evaluating the efficacy, safety, tolerability and pharmacokinetics of glofitamab. In this study, glofitamab is assessed as a single agent and in combination with Gazyva/Gazyvaro (obinutuzumab), following pre-treatment with a one-time, fixed dose of Gazyva/Gazyvaro, in people with relapsed or refractory B-cell non-Hodgkin lymphoma. Outcome measures include overall response rate, complete response rate per Lugano 2014 criteria, maximum tolerated dose, and tolerability.

About Roche in haematology
Roche has been developing medicines for people with malignant and non-malignant blood diseases for over 20 years; our experience and knowledge in this therapeutic area runs deep. Today, we are investing more than ever in our effort to bring innovative treatment options to patients across a wide range of haematologic diseases. Our approved medicines include MabThera/Rituxan (rituximab), Gazyva/Gazyvaro (obinutuzumab), Polivy (polatuzumab vedotin), Venclexta/Venclyxto (venetoclax) in collaboration with AbbVie, and Hemlibra (emicizumab). Our pipeline of investigational haematology medicines includes idasanutlin, a small molecule which inhibits the interaction of MDM2 with p53; T-cell engaging bispecific antibodies, glofitamab and mosunetuzumab, targeting both CD20 and CD3, Tecentriq (atezolizumab), a monoclonal antibody designed to bind with PD-L1; and crovalimab, an anti-C5 antibody engineered to optimise complement inhibition. Our scientific expertise, combined with the breadth of our portfolio and pipeline, also provides a unique opportunity to develop combination regimens that aim to improve the lives of patients even further.