On November 3, 2022 MorphoSys U.S. Inc., a fully owned subsidiary of MorphoSys AG (FSE: MOR; NASDAQ: MOR), reported that new data on pelabresib, an investigational BET inhibitor, and tafasitamab, marketed in the U.S. as Monjuvi and outside the U.S. by Incyte as Minjuvi, will be featured in 14 presentations – including four oral sessions – during the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in New Orleans, Louisiana from December 10-13, 2022 (Press release, MorphoSys, NOV 3, 2022, View Source [SID1234622940]).

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"The comprehensive set of data we’re presenting at ASH (Free ASH Whitepaper) reaffirms our confidence in our ongoing pivotal studies, including MANIFEST-2 and frontMIND, that are evaluating whether these investigational therapies can enhance the standard of care for patients with difficult-to-treat blood cancers," said Tim Demuth, M.D., Ph.D., MorphoSys Chief Research and Development Officer. "We are committed to helping patients who need better options for first-line treatment and beyond. These latest presentations showcase the quality of science and potential solutions coming out of our research and development efforts."

Key data being presented at ASH (Free ASH Whitepaper) 2022 will include:

An oral presentation on results from the ongoing Phase 2 MANIFEST study evaluating clinical benefit and biomarker changes, indicating potential disease modification following treatment with pelabresib as monotherapy or in combination with ruxolitinib in patients with myelofibrosis.
An oral presentation from the ongoing Phase 2 MANIFEST study highlighting durability of response and safety beyond 24 weeks for pelabresib in combination with ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis.
An oral presentation and a poster presentation on minimal residual disease (MRD)-negativity to serve as a potential surrogate endpoint and predictor of outcomes after front-line therapy with tafasitamab plus lenalidomide and R-CHOP in diffuse large B-cell lymphoma (DLBCL).
A poster presentation of final, 18-month data from the firstMIND study to assess the safety of tafasitamab or tafasitamab plus lenalidomide and R‑CHOP in patients with newly diagnosed DLBCL, including data on overall response rates, duration of response and progression-free survival rates in MRD-negative patients.
A poster presentation of an additional data analysis from the L-MIND study that offers further insight into the safety and long-term use of tafasitamab in patients with relapsed or refractory DLBCL, including data on the duration of response in patients who have undergone treatment for at least two years, some of whom have been treated for five years or more.
ASH 2022 Accepted Abstracts

Abstracts listed below include both MorphoSys-led and partner abstracts.

Abstract Title Abstract Number Date/Time
Pelabresib
ORAL
Pelabresib (CPI-0610) Combined With Ruxolitinib for JAK Inhibitor Treatment-Naïve Patients With Myelofibrosis: Durability of Response and Safety Beyond Week 24 #238
Saturday, December 10, 2022
2:45 p.m. CST / 9:45 p.m. CET
ORAL
Clinical Benefit Associated With Biomarker Changes Indicative of Disease Modification in Patients With Myelofibrosis Treated With the BET Inhibitor Pelabresib as Monotherapy or in Combination With Ruxolitinib #630
Sunday, December 11, 2022
5:45 p.m. CST / 12:45 a.m. CET on December 12, 2022

POSTER
Pelabresib (CPI-0610) as Add-on to Ruxolitinib in Myelofibrosis: Durability of Response and Safety Beyond Week 24 in the Phase 2 MANIFEST Study #4344
Monday, December 12, 2022
6:00 p.m. CST / 1:00 a.m. CET on December 13, 2022
PUBLICATION
Improvement in Individual Symptoms and Total Symptom Score (TSS) and Matching-Adjusted Indirect Comparison (MAIC) Analysis to Compare TSS as a Continuous Endpoint in Patients With Myelofibrosis Treated With Pelabresib in Combination With Ruxolitinib Versus Janus Kinase Inhibitor Monotherapy
N/A N/A

Tafasitamab
ORAL
MRD-negativity as a potential surrogate endpoint after frontline DLBCL therapy: pooled analysis & implications for clinical trial design #322
Saturday, December 10, 2022
4:45 p.m. CST / 11:45 p.m. CET

ORAL
CD19 antigen occupancy on cancer cells with the CD19 monoclonal antibody tafasitamab improves the activation, antitumor efficacy, and safety profile of CART19 cell therapy #977 Monday, December 12, 2022
5:30 p.m. CST / 12:30 a.m. CET on December 13, 2022
POSTER
firstMIND: Final Analysis from a PhaseIb, Open-Label, Randomized Study to Assess Safety of Tafasitamab or Tafasitamab + Lenalidomide in Addition to RCHOP in Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma #1619
Saturday, December 10, 2022
5:30 p.m. CST / 12:30 a.m. CET on December 11, 2022
POSTER
frontMIND: A Phase III, Multicenter, Randomized, Double-Blind Study of Tafasitamab + Lenalidomide + R-CHOP versus R-CHOP Alone for Newly Diagnosed High-Intermediate and High-Risk Diffuse Large B-Cell Lymphoma #2947 Sunday, December 11, 2022
6:00 p.m. CST / 1:00 a.m. CET on December 12, 2022
POSTER
L-MIND: A Safety and Efficacy Analysis of Tafasitamab in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL) Receiving Treatment for at Least 2 Years #2937
Sunday, December 11, 2022
6:00 p.m. CST / 1:00 a.m. CET on December 12, 2022
POSTER
Relationship of Ultrasensitive ctDNA MRD & Outcomes in DLBCL after Frontline Therapy with Tafasitamab in Combination with Lenalidomide & R-CHOP #1519 Saturday, December 10, 2022
5:30 p.m. CST / 12:30 a.m. CET on December 11, 2022
POSTER
Blocking the CD47-SIRPa Axis enhances Tafasitamab-mediated phagocytosis #4185 Monday, December 12, 2022
6:00 p.m. CST / 1:00 a.m. CET on December 13, 2022
POSTER
Management of Canadian Patients (Pts) with Relapsed/Refractory Diffuse Large B-cell Lymphoma (R/R DLBCL) in the Real-World #1656
Saturday, December 10, 2022
5:30 p.m. CST / 12:30 a.m. CET on December 11, 2022
PUBLICATION
Tafasitamab (TAFA) Plus Lenalidomide (LEN) Prior to Chimeric Antigen Receptor T-Cell (CAR-T) Therapy in Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL): Case Series of Eight Patients (Pts) N/A N/A

PUBLICATION
A Phase 3 Study of Tafasitamab Plus Lenalidomide in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (firmMIND) N/A N/A

Please refer to the ASH (Free ASH Whitepaper) online program for full session details and data presentation listings and visit the MorphoSys booth #3115 onsite. MorphoSys is also proud to support a symposium titled "Real-world, real innovation in DLBCL: perspectives on integrating novel antibody platforms into patient care" on Friday, December 9 from 7:00 a.m. – 9:00 a.m. CST at the Sheraton New Orleans in the Rhythms Ballroom.

About MorphoSys
At MorphoSys, we are driven by our mission: More life for people with cancer. As a global commercial-stage biopharmaceutical company, we use groundbreaking science and technologies to discover, develop, and deliver innovative cancer medicines to patients. MorphoSys is headquartered in Planegg, Germany, and has its U.S. operations anchored in Boston, Massachusetts. To learn more, visit us at www.morphosys.com and follow us on Twitter and LinkedIn.

About Pelabresib
Pelabresib (CPI-0610) is an investigational selective small molecule designed to promote anti-tumor activity by inhibiting the function of bromodomain and extra-terminal domain (BET) proteins to decrease the expression of abnormally expressed genes in cancer. Pelabresib is being investigated as a treatment for myelofibrosis and has not yet been evaluated or approved by any regulatory authorities.

About MANIFEST
MANIFEST (NCT02158858) is an open-label Phase 2 clinical trial of pelabresib in patients with myelofibrosis.

The MANIFEST trial is evaluating pelabresib in combination with ruxolitinib in JAK-inhibitor-naïve myelofibrosis patients (Arm 3), with a primary endpoint of the proportion of patients with a ≥35% spleen volume reduction from baseline (SVR35) after 24 weeks of treatment. The trial is also evaluating pelabresib either as a monotherapy in patients who are resistant to, intolerant of, or ineligible for ruxolitinib and no longer on the drug (Arm 1) or as add-on therapy in combination with ruxolitinib in patients with a suboptimal response to ruxolitinib or myelofibrosis progression (Arm 2). Patients in Arms 1 and 2 are being stratified based on transfusion-dependent (TD) status. The primary endpoint for the patients in cohorts 1A and 2A, who were TD at baseline, is conversion to transfusion independence for 12 consecutive weeks. The primary endpoint for patients in cohorts 1B and 2B, who were not TD at baseline, is the proportion of patients with a ≥35% spleen volume reduction from baseline after 24 weeks of treatment.

Constellation Pharmaceuticals, Inc., a MorphoSys company, is the MANIFEST trial sponsor.

About MANIFEST-2
MANIFEST-2 (NCT04603495) is a global, double-blind, randomized Phase 3 clinical trial with pelabresib in combination with ruxolitinib versus placebo plus ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis. The primary endpoint of the study is a 35% or greater reduction in spleen volume (SVR35) from baseline at 24 weeks. A key secondary endpoint of the study is a 50% or greater improvement in total symptom score (TSS50) from baseline at 24 weeks.

Constellation Pharmaceuticals, Inc., a MorphoSys company, is the MANIFEST-2 trial sponsor.

About Monjuvi (tafasitamab-cxix)
Tafasitamab is a humanized Fc-modified CD19 targeting immunotherapy. In 2010, MorphoSys licensed exclusive worldwide rights to develop and commercialize tafasitamab from Xencor, Inc. Tafasitamab incorporates an XmAb engineered Fc domain, which mediates B-cell lysis through apoptosis and immune effector mechanism including Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) and Antibody-Dependent Cellular Phagocytosis (ADCP).

In the United States, Monjuvi (tafasitamab-cxix) is approved by the U.S. Food and Drug Administration in combination with lenalidomide for the treatment of adult patients with relapsed or refractory DLBCL not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT). This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

In Europe, Minjuvi (tafasitamab) received conditional marketing authorization in combination with lenalidomide, followed by Minjuvi monotherapy, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for autologous stem cell transplant (ASCT).

Tafasitamab is being clinically investigated as a therapeutic option in B-cell malignancies in several ongoing combination trials.

Monjuvi and Minjuvi are registered trademarks of MorphoSys AG. Tafasitamab is co-marketed by Incyte and MorphoSys under the brand name Monjuvi in the U.S., and marketed by Incyte under the brand name Minjuvi in Europe, the UK and Canada.

XmAb is a registered trademark of Xencor, Inc.

About L-MIND
The L-MIND (NCT02399085) trial is a single arm, open-label Phase 2 study investigating the combination of tafasitamab and lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have had at least one, but no more than three prior lines of therapy, including an anti-CD20 targeting therapy (e.g., rituximab), who are not eligible for high-dose chemotherapy or refuse subsequent autologous stem cell transplant. The study’s primary endpoint is overall response rate (ORR). Secondary outcome measures include duration of response (DoR), progression-free survival (PFS) and overall survival (OS). In May 2019, the study reached its primary completion.

About frontMIND
The frontMIND (NCT04824092) trial is a randomized, double-blind, placebo-controlled, global Phase 3 clinical study in previously untreated high-intermediate and high-risk DLBCL patients that is conducted in partnership with the German Lymphoma Association (GLA), the Italian Lymphoma study group and the US Oncology Network.

The study aims to enroll approximately 880 DLBCL patients to receive either tafasitamab plus lenalidomide in addition to rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) or R-CHOP alone. The primary endpoint is investigator-assessed progression-free survival, according to Lugano 2014 criteria, and key secondary endpoints include event-free survival by investigator, overall survival, metabolic complete response rate by a Blinded Independent Review Committee, and overall response rate.

About firstMIND
The firstMIND (NCT04134936) trial is a Phase 1b, randomized study of tafasitamab + R-CHOP (Arm A) or tafasitamab + lenalidomide + R-CHOP (Arm B) in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). The study includes a safety run-in phase and a main phase (n=66). In the safety run-in phase, 24 patients were enrolled. The primary objective is to assess safety; secondary objectives include objective response rate, PET negative complete response (PET-CR) rate at end of treatment, progression-free survival, event-free survival, long-term safety, pharmacokinetics and immunogenicity of tafasitamab.

Important Safety Information

What are the possible side effects of MONJUVI?
MONJUVI may cause serious side effects, including:

– Infusion reactions. Your healthcare provider will monitor you for infusion reactions during your infusion of MONJUVI. Tell your healthcare provider right away if you get fever, chills, rash, flushing, headache, or shortness of breath during an infusion of MONJUVI.

– Low blood cell counts (platelets, red blood cells, and white blood cells). Low blood cell counts are common with MONJUVI, but can also be serious or severe. Your healthcare provider will monitor your blood counts during treatment with MONJUVI. Tell your healthcare provider right away if you get a fever of 100.4 F (38 C) or above, or any bruising or bleeding.

– Infections. Serious infections, including infections that can cause death, have happened in people during treatments with MONJUVI and after the last dose. Tell your healthcare provider right away if you get a fever of 100.4 F (38 C) or above, or develop any signs and symptoms of an infection.

The most common side effects of MONJUVI include:

– Feeling tired or weak

– Diarrhea

– Cough

– Fever

– Swelling of lower legs or hands

– Respiratory tract infection

– Decreased appetite

These are not all the possible side effects of MONJUVI.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Before you receive MONJUVI, tell your healthcare provider about all your medical conditions, including if you:

– Have an active infection or have had one recently.

– Are pregnant or plan to become pregnant. MONJUVI may harm your unborn baby. You should not become pregnant during treatment with MONJUVI. Do not receive treatment with MONJUVI in combination with lenalidomide if you are pregnant because lenalidomide can cause birth defects and death of your unborn baby.

– You should use an effective method of birth control (contraception) during treatment and for at least 3 months after your final dose of MONJUVI.

– Tell your healthcare provider right away if you become pregnant or think that you may be pregnant during treatment with MONJUVI.

– Are breastfeeding or plan to breastfeed. It is not known if MONJUVI passes into your breastmilk. Do not breastfeed during treatment for at least 3 months after your last dose of MONJUVI.

You should also read the lenalidomide Medication Guide for important information about pregnancy, contraception, and blood and sperm donation.

Tell your healthcare provider about all the medications you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Please see the full Prescribing Information for Monjuvi, including Patient Information, for additional Important Safety Information.

On November 3, 2022 Precision BioSciences, Inc. (Nasdaq: DTIL), a clinical stage gene editing company developing ARCUS-based ex vivo allogeneic CAR T and in vivo gene editing therapies, reported that an abstract on the effective cell dose and functional attributes of the company’s lead CD19 candidate, Azercabtagene Zapreleucel (azer-cel) was accepted for poster presentation at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, being held December 10-13, 2022 in New Orleans, Louisiana (Press release, Precision Biosciences, NOV 3, 2022, View Source [SID1234622939]). Precision is currently evaluating azer-cel in a Phase 1/2a clinical trial of adult subjects with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) who relapsed following treatment with an autologous CAR T.

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"We look forward to seeing this data presented at the ASH (Free ASH Whitepaper) meeting and highlighting the differentiated product cellular attributes including product composition and cell doses that contribute to optimized efficacy and safety of azer-cel. This is the first analysis of an allogeneic CD19 CAR T product composition to demonstrate that strategies to maximize naïve cell phenotype may lead to improved safety and efficacy of an allogenic CAR T therapy," said Alan List, M.D., Chief Medical Officer of Precision BioSciences.

Poster Presentation Details:

Title: Effective Cell Dose and Functional Attributes of Azercabtagene Zapreleucel (azer-cel; PBCAR0191) Associate with Allogeneic CAR T-Cell Safety and Efficacy in Patients with Relapsed/Refractory B-Cell Lymphoma
First Author: Caron A. Jacobson, M.D., Dana Farber Cancer Institute
Poster Session: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: Poster I
Abstract #: 2005
Date/Time: Saturday, December 10, 2022, 5:30 PM – 7: 30 PM ET
Location: Ernest N. Morial Convention Center, Hall D

On November 3, 2022 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS’’ or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, reported that the Company will present data relating to its highly selective CDK9 inhibitor, GFH009, during two poster presentations at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting being held on December 10-13, 2022 in New Orleans, Louisiana (Press release, Sellas Life Sciences, NOV 3, 2022, View Source [SID1234622938]). The meeting will also take place virtually.

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During the first poster presentation, SELLAS will share data related to GFH009’s mechanism of action associated anti-proliferative activity in various hematologic malignancies. The second poster presentation highlights preliminary safety and efficacy data from the first-in-human study of GFH009 in patients with relapsed / refractory hematologic malignancies.

On November 3, 2022 Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) reported the upcoming presentation of five posters highlighting data from the Company’s commercial and clinical-stage hematology-oncology portfolio at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition being held December 10-13, 2022, in New Orleans, LA, and virtually (Press release, Rigel, NOV 3, 2022, View Source [SID1234622937]).

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The abstract titled "Olutasidenib (FT-2102) induces durable complete remissions in patients with relapsed/refractory mIDH1 acute myeloid leukemia: Results from a planned interim analysis of a phase 2 pivotal clinical trial" provides an updated interim analysis from the open-label Phase 2 registrational study of olutasidenib, an investigational, oral, small molecule inhibitor of mutant isocitrate dehydrogenase-1 (mIDH1), in patients with relapsed/refractory acute myeloid leukemia (R/R AML). The registrational cohort of the Phase 2 study enrolled 153 patients with mIDH1 R/R AML who received olutasidenib monotherapy 150 mg twice daily. The efficacy evaluable population was 147 patients who received their first dose at least six months prior to the interim analysis cutoff date of June 18, 2021. The primary endpoint was a composite of complete remission (CR) plus complete remission with partial hematological recovery (CRh). CRh is defined as less than 5% blasts in the bone marrow, no evidence of disease, and partial recovery of peripheral blood counts (platelets >50,000/microliter and absolute neutrophil count >500/microliter).

Results from the updated interim analysis of patients with mIDH1 R/R AML demonstrated a 35% CR+CRh rate with a median duration of 25.9 months. The observed activity is clinically meaningful and potentially represents a new therapeutic option in the treatment of this poor prognosis patient population. In this cohort, olutasidenib was well tolerated with an adverse event profile largely characteristic of symptoms or conditions experienced by patients with AML undergoing treatment. Differentiation syndrome was observed and manageable in most cases with dose interruption and corticosteroids. Increases in liver function parameters were manageable with dose modifications and concomitant medications.

"We are thrilled with these updated results from the olutasidenib registrational trial, which demonstrate a median duration of CR+CRh of 25.9 months, and potentially represents an improvement for patients with mIDH1 R/R AML. The totality of these efficacy and safety data underscore the potential for olutasidenib to be a meaningful new treatment option for these patients who are currently underserved," said Raul Rodriguez, Rigel’s president and CEO. "In addition to the olutasidenib data, we are pleased to see data presented from across our hematology-oncology portfolio, demonstrating our strength in this space."

A New Drug Application (NDA) for olutasidenib for the treatment of mIDH1 R/R AML is currently under review by the U.S. Food and Drug Administration (FDA) with a Prescription Drug User Fee Act (PDUFA) target action date of February 15, 2023.

Poster Presentations

Abstract #: 2757
Title: Olutasidenib (FT-2102) induces durable complete remissions in patients with relapsed/refractory mIDH1 acute myeloid leukemia: Results from a planned interim analysis of a phase 2 pivotal clinical trial
Presenter: Jorge E. Cortes, M.D., Director, Georgia Cancer Center, Cecil F. Whitaker Jr., GRA Eminent Scholar Chair in Cancer, and Phase 2 Trial Investigator
Session Name: 616. Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster II
Date: Sunday, December 11, 2022
Presentation Time: 6:00-8:00 PM CT
Location: Ernest N. Morial Convention Center, Hall D

Abstract #: 2250
Title: The safety and efficacy of fostamatinib in patients with chronic immune thrombocytopenic purpura treated in a real-world community hematology setting
Presenter: Mehdi M. Moezi, MD, Cancer Specialists of North Florida
Session Name: 904. Outcomes Research—Non-Malignant Conditions: Poster I
Date: Saturday, December 10, 2022
Presentation Time: 5:30-7:30 PM CT
Location: Ernest N. Morial Convention Center, Hall D

Abstract #: 1011
Title: Phase 3, randomized, double-blind, placebo-controlled, global study (FORWARD) of fostamatinib for the treatment of warm antibody autoimmune hemolytic anemia
Presenter: David J. Kuter, M.D., DPhil, Director of Clinical Hematology at Massachusetts General Hospital, Professor of Medicine at Harvard Medical School, FORWARD Trial Lead Investigator
Session Name: 101. Red Cells and Erythropoiesis, Excluding Iron: Poster I
Date: Saturday, December 10, 2022
Presentation Time: 5:30-7:30 PM CT
Location: Ernest N. Morial Convention Center, Hall D

Abstract #: 3724
Title: SYK kinase as a master regulator of NETosis
Presenter: Vadim V. Markovtsov, PhD, MS, Rigel Pharmaceuticals, Inc.
Session Name: 201. Granulocytes, Monocytes, and Macrophages: Poster III
Date: Monday, December 12, 2022
Presentation Time: 6:00-8:00 PM CT
Location: Ernest N. Morial Convention Center, Hall D

Abstract #: 1132
Title: Comparative Effectiveness of Fostamatinib Vs. Rituximab in Refractory Chronic Immune Thrombocytopenia: A Network Meta-Analysis
Presenter: Vickie McDonald, MD, Consultant Haematologist at Barts Health NHS Trust
Session Name: 311. Disorders of Platelet Number or Function: Clinical and Epidemiological: Poster I
Date: Saturday, December 10, 2022
Presentation Time: 5:30-7:30 PM CT
Location: Ernest N. Morial Convention Center, Hall D

The conference abstracts can be accessed here.

To learn more about Rigel Pharmaceuticals and the Company’s clinical and commercial heme-onc portfolio visit booth #2815 during ASH (Free ASH Whitepaper) 2022.

About Olutasidenib & AML
Olutasidenib is an oral, small molecule investigational agent designed to selectively bind to and inhibit mutated IDH1 enzymes. This targeted agent has the potential to provide therapeutic benefit by reducing 2-HG levels and restoring normal cellular differentiation. IDH1 is a natural enzyme that is part of the normal metabolism of all cells. When mutated, IDH1 activity can promote blood malignancies and solid tumors. IDH1 mutations are present in 6 to 9 percent of patients with AML.1

Acute myeloid leukemia (AML) is a rapidly progressing cancer of the blood and bone marrow that affects myeloid cells, which normally develop into various types of mature blood cells. AML occurs primarily in adults and accounts for about 1 percent of all adult cancers. The American Cancer Society estimates that in the United States alone, there will be about 20,050 new cases, most in adults, in 2022.2 Relapsed AML affects about half of all patients who, following treatment and remission, experience a return of leukemia cells in the bone marrow.3 Refractory AML, which affects between 10 and 40 percent of newly diagnosed patients, occurs when a patient fails to achieve remission even after intensive treatment.4 Quality of life declines for patients with each successive line of treatment for AML, and well tolerated treatments in relapsed and refractory disease remain an unmet need.

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 AIHA
Autoimmune hemolytic anemia (AIHA) is a rare, serious blood disorder in which the immune system produces antibodies that lead to the destruction of the body’s own red blood cells. Warm antibody AIHA (wAIHA), which is the most common form of AIHA, is characterized by the presence of antibodies that react with the red blood cell surface at body temperature. wAIHA affects approximately 36,000 adult patients in the U.S.5 and can be a severe, debilitating disease. To date, there are no disease-targeted therapies approved for wAIHA, 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.

On November 3, 2022 Biomea Fusion, Inc. (Nasdaq: BMEA), a clinical-stage biopharmaceutical company dedicated to discovering and developing novel covalent small molecules to treat and improve the lives of patients with genetically defined cancers and metabolic diseases, reported it will present preclinical data of investigational covalent FLT3 inhibitor, BMF-500, at the 64th ASH (Free ASH Whitepaper) Annual Meeting, which will be held from December 10-13, 2022, at the Ernest N. Morial Convention Center in New Orleans, Louisiana (Press release, Biomea Fusion, NOV 3, 2022, View Source [SID1234622936]).

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BMF-500 was discovered and developed in-house at Biomea using the company’s proprietary FUSION System and designed to have a therapeutic profile to allow for combinations with standard of care and/or novel targeted agents like BMF-219, Biomea’s investigational covalent menin inhibitor. The company is on track to submit an investigational new drug (IND) application for BMF-500 in the first half of 2023 and, subject to the successful clearance of an investigational new drug (IND) application, plans to initiate clinical trials evaluating BMF-500 as a single agent and in novel combinations.

"We believe the preclinical data we will present at ASH (Free ASH Whitepaper) has the potential to establish BMF-500 as the most potent and selective FLT3 inhibitor reported to date. BMF-500’s unique profile and robust preclinical data demonstrate our growing expertise in developing next-generation covalently binding small molecules through our FUSIONTM System," said Dr. Steve Morris, Biomea’s CMO. "Given the picomolar activity against key isoforms of FLT3, high specificity to FLT3, and the potential to combine with other agents, including our own novel menin inhibitor, BMF-219, we believe BMF-500 has the potential to produce deep and durable remissions in patients with FLT3 mutant AML."

Presentation Details

Session Name: 616. Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster II
Session Date: Sunday, December 11, 2022
Presentation Time: 6:00 PM – 8:00 PM (CST)
Publication Number: 2756
Title: BMF-500: An Orally Bioavailable Covalent Inhibitor of FLT3 with High Selectivity and Potent Antileukemic Activity in FLT3-Mutated AML

Full Text of Abstract:
Activating mutations of the FMS-like tyrosine kinase 3 (FLT3) are the most frequent genetic alteration in AML and are associated with poor prognosis. Though several FLT3 inhibitors have entered clinical trials and reached commercialization, adverse events and dose-limiting toxicities often restrict the therapeutic window and limit their long-term use. Such limitations impact the ability to achieve long-lasting response in patients and ultimately result in therapy-induced resistance. Exquisite potency combined with high selectivity and improved safety profile is expected to help improve tolerance and overall treatment outcomes of FLT3-targeted therapy.

BMF-500 was designed as a highly potent and selective, covalent, small molecule inhibitor of FLT3, that binds irreversibly to a reactive cysteine in the kinase active site. BMF-500 is a picomolar inhibitor with markedly improved potency over gilteritinib, a reversible inhibitor of FLT3. BMF-500 selectively killed AML cells harboring FLT3 activating mutations, including MV4-11 and MOLM-13, and engineered cells expressing FLT3 internal tandem duplications (FLT3-ITD) and/or FLT3 tyrosine kinase domain (TKD) mutations. In ex vivo cultures, BMF-500 as a single agent induced potent growth inhibition of patient-derived AML cells harboring either FLT3-ITD or FLT3 non-ITD mutations.

The potent covalent inhibition of FLT3 by BMF-500 manifested in effective and durable cellular response that was improved over gilteritinib. For example, a 3-hour exposure followed by wash-out of BMF-500 outperformed 4 days of continuous exposure to gilteritinib, at all concentrations tested. In cells harboring FLT3 activating mutations, BMF-500 induced dose-dependent inhibition of FLT3 phosphorylation and downstream signaling, including phospho-STAT5 and phospho-ERK. A 1-hour pulse treatment with BMF-500 was sufficient to achieve deep and durable target inhibition for greater than 24 hours, an effect not observed with gilteritinib under similar conditions. Profiling BMF-500 across a broad panel of kinases and key cell-surface receptors revealed high selectivity for FLT3 mutants and selectivity against cKit.

Potent FLT3 inhibition and high selectivity of BMF-500 translated to sustained tumor regression and improved survival in both subcutaneous and disseminated xenograft models of mutant FLT3-driven AML. Orally administered BMF-500 was well tolerated over 4 weeks of dosing. Study results including efficacy and PD response will be presented.

Collectively these data demonstrate BMF-500 to be a novel FLT3 inhibitor with best-in-class potential, given its efficacy, durability, and selectivity in comparison to existing FLT3 inhibitors.

About FLT3 (fms-like tyrosine kinase 3)

FLT3 is a tyrosine kinase receptor that plays a central role in the survival, proliferation, and differentiation of immature blood cells. Notably, FLT3 gene mutations are common in patients with AML and are associated with a poor prognosis. Nearly 30% of AML patients have a FLT3 mutation, representing more than 6,000 incident patients in the United States each year. While FLT3-specific and pan-tyrosine kinase inhibitors are approved by the FDA across various lines of therapy in AML, these agents have produced relatively low rates of durable responses and overall survival remains an unmet need.