On December 4, 2018 Nordic Nanovector ASA (OSE: NANO) reported that two new poster presentations from preclinical studies with CD37-targeting radioimmunotherapies were made at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition (1-4 December 2018 in San Diego, CA, USA) (Press release, Nordic Nanovector, DEC 4, 2018, View Source [SID1234553485]). These posters were presented in addition to the results of the Phase 1/2 trial of Betalutin (177Lu-satetraxetan-lilotomab) in patients with relapsed/refractory indolent non-Hodgkin’s lymphoma – see separate announcement.

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The posters are as follows:

Abstract 4422

Abstract title:

Targeted Alpha Therapy with 212Pb-NNV-003 for the Treatment of CD37 Positive B-Cell Chronic Lymphocytic Leukemia (CLL) and Non-Hodgkin Lymphoma (NHL)

Authors:

A. Saidi et al.

This poster describes results from a research collaboration to develop a novel CD37-targeting alpha therapy for B-cell malignancies and the results noted in the abstract were previously announced on 1 November 2018. The research collaboration was established in June 2015 with Orano Med (formerly known as AREVA Med) to develop and investigate a next-generation targeted alpha therapy, comprising Nordic Nanovector’s chimeric anti-CD37 antibody (NNV003) and lead-212 (212Pb), for the treatment of B-cell malignancies.

The preclinical studies investigated the dose-dependent efficacy and tolerability of 212Pb-NNV003 in human cell and mouse models of chronic lymphocytic leukaemia (CLL) and Burkitt’s lymphoma (a type of non-Hodgkin’s lymphoma, NHL). In the studies, 212Pb-NNV003 was found to be well tolerated and led to a 90-100% survival rate in mouse models of CLL and NHL.

Abstract 1371

Abstract title:

Cell Cycle Kinase Inhibitors Potentiate the Effect of 177lu-Lilotomab Satetraxetan in Treatment of Aggressive Diffuse Large B-Cell Lymphoma Cell Lines

Authors:

G.E. Rødland et al.

The poster describes results from a preclinical study aimed at identifying possible drug combinations involving Betalutin in two aggressive, radioimmunotherapy-resistant diffuse large B-cell lymphoma (DLBCL) cell lines. The study identified cell cycle kinase inhibitors as promising partners for combination treatment of aggressive DLBCL with Betalutin, warranting further exploration in preclinical models.

Both abstracts are available at View Source and the posters have been published on the Nordic Nanovector website – View Source

About ASH (Free ASH Whitepaper)

The ASH (Free ASH Whitepaper) annual meeting is the premier event for scientific exchange in the field of haematology, attracting more than 20,000 attendees from all over the world. Typically, more than 5,000 scientific abstracts are submitted each year, and more than 3,000 abstracts are accepted for oral and poster presentations through an extensive peer review process.

On December 4, 2018 AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, reported its results from the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN), National Cancer Institute (NCI)-sponsored, Phase 3 study (E1912) evaluating IMBRUVICA (ibrutinib) plus rituximab versus the current National Comprehensive Cancer Network (NCCN) guidelines Category 1 treatment of fludarabine, cyclophosphamide and rituximab (FCR) in previously untreated younger patients (70 years old or younger) with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) (Press release, AbbVie, DEC 4, 2018, View Source [SID1234531879]).1,2 This interim analysis showed that IMBRUVICA plus rituximab significantly prolonged progression-free survival (PFS), the primary endpoint of the study, compared to FCR, with a 65 percent reduction in risk of progression or death. Furthermore, IMBRUVICA plus rituximab significantly improved overall survival (OS) compared to FCR. The findings were presented today during the Late-Breaker abstract oral session at the 2018 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego, CA (abstract #LBA-4).

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This study evaluated 529 patients in the United States from centers spanning four cooperative groups. The study was led by ECOG-ACRIN with additional study site participation by SWOG, ALLIANCE and NRG Oncology, and was sponsored by the NCI in collaboration with Pharmacyclics LLC, an AbbVie company, through the existing Cooperative Research and Development Agreement with NCI. IMBRUVICA is a once-daily, first-in-class BTK inhibitor that is administered orally, and is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.

"We have been eagerly awaiting a new treatment regimen that could help younger chronic lymphocytic leukemia patients. These findings further support IMBRUVICA-based therapy as an efficacious first-line treatment for many patients with CLL," said Danelle James, M.D., M.A.S., Head of Clinical Science, Pharmacyclics LLC, an AbbVie company. "We are proud to participate and collaborate with the National Cancer Institute and the Division of Cancer Treatment."

At a median follow-up of 33.4 months, IMBRUVICA plus rituximab showed superior PFS compared to FCR in younger and previously untreated CLL patients (HR: 0.35; 95% confidence interval [CI]: 0.22-0.56; p<0.0001). The study also demonstrated an improved OS for the IMBRUVICA plus rituximab treatment arm versus FCR (HR: 0.17; 95% CI: 0.05-0.54; p=0.0003).

CLL is one of the two most common forms of leukemia in adults and is a type of cancer that can develop from cells in the bone marrow that later mature into certain white blood cells (called lymphocytes).3 While these cancer cells start in the bone marrow, they then later spread into the blood. The prevalence of CLL is approximately 115,000 patients in the U.S. with approximately 20,000 newly diagnosed patients every year.4,5 CLL is predominately a disease of the elderly, with a median age at diagnosis ranging from 65-70 years.6

About Abstract #LBA-4: A Randomized Phase III Study of Ibrutinib (PCI-32765)-Based Therapy Vs. Standard Fludarabine, Cyclophosphamide, and Rituximab (FCR) Chemoimmunotherapy in Untreated Younger Patients with Chronic Lymphocytic Leukemia (CLL): A Trial of the ECOG-ACRIN Cancer Research Group (E1912)

Late-Breaker Oral Presentation: Tuesday, December 4 at 7:30am PT

The Phase 3 study (E1912) evaluated previously untreated CLL patients age 70 or younger, who were randomly assigned to receive IMBRUVICA (420 mg/day until disease progression) and rituximab (50 mg/m2 on day 1 of cycle 2; 325 mg/m2 on day 2 of cycle 2; 500 mg/m2 on day 1 of cycles 3-7) (n=354) or six courses of intravenous fludarabine (25 mg/m2) and cyclophosphamide (250 mg/m2) days 1-3 with rituximab (50 mg/m2 on day 1 of cycle 1; 325 mg/m2 on day 2 of cycle 1; 500 mg/m2 on day 1 of cycles 2-6) every 28-days (n=175). The primary endpoint was PFS with a secondary endpoint of OS.

With a median follow-up of 33.4 months, the pre-determined, interim analysis observed 77 PFS events and 14 deaths. IMBRUVICA plus rituximab significantly improved PFS compared to FCR (HR: 0.35; 95% CI: 0.22-0.56; p<0.0001), which crossed the pre-specified boundary. The IMBRUVICA plus rituximab treatment arm also significantly improved OS compared to FCR (HR: 0.17; 95% CI: 0.05-0.54; p=0.0003, pre-specified boundary for superiority p=0.0005).

FCR was more frequently associated with Grade 3 and 4 neutropenia (FCR: 44 percent vs. IMBRUVICA plus rituximab: 23 percent; p<0.0001) and infectious complications (FCR: 18 percent vs. IMBRUVICA plus rituximab: 7 percent; p<0.0001). Grade 3 and 4 treatment-related adverse events were observed in 58 percent of IMBRUVICA plus rituximab treated patients and 72 percent of FCR treated patients (p=0.0042).

To view all IMBRUVICA company-sponsored or investigator-initiated studies being presented at ASH (Free ASH Whitepaper) 2018, please visit: View Source

About IMBRUVICA
IMBRUVICA (ibrutinib) is a first-in-class, oral, once-daily therapy that mainly works by inhibiting a protein called Bruton’s tyrosine kinase (BTK). BTK is a key signaling molecule in the B-cell receptor signaling complex that plays an important role in the survival and spread of malignant B cells.7 IMBRUVICA blocks signals that tell malignant B cells to multiply and spread uncontrollably.

IMBRUVICA is FDA-approved in six distinct patient populations: chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), Waldenström’s macroglobulinemia (WM), along with previously-treated mantle cell lymphoma (MCL), previously-treated marginal zone lymphoma (MZL) and previously-treated chronic graft-versus-host disease (cGVHD).8

IMBRUVICA was first approved for adult patients with MCL who have received at least one prior therapy in November 2013.
Soon after, IMBRUVICA was initially approved in adult CLL patients who have received at least one prior therapy in February 2014. By July 2014, the therapy received approval for adult CLL patients with 17p deletion, and by March 2016, the therapy was approved as a frontline CLL treatment.
IMBRUVICA was approved for adult patients with WM in January 2015.
In May 2016, IMBRUVICA was approved in combination with bendamustine and rituximab (BR) for adult patients with CLL/SLL.
In January 2017, IMBRUVICA was approved for adult patients with MZL who require systemic therapy and have received at least one prior anti-CD20-based therapy.
In August 2017, IMBRUVICA was approved for adult patients with cGVHD that failed to respond to one or more lines of systemic therapy.
In August 2018, IMBRUVICA plus rituximab was approved for adult patients with WM.
Accelerated approval was granted for the MCL and MZL indications based on overall response rate. Continued approval for MCL and MZL may be contingent upon verification and description of clinical benefit in confirmatory trials.

IMBRUVICA has been granted four Breakthrough Therapy Designations from the U.S. FDA. This designation is intended to expedite the development and review of a potential new drug for serious or life-threatening diseases.9 IMBRUVICA was one of the first medicines to receive FDA approval via the new Breakthrough Therapy Designation pathway.

IMBRUVICA is being studied alone and in combination with other treatments in several blood and solid tumor cancers and other serious illnesses. IMBRUVICA has one of the most robust clinical oncology development programs for a single molecule in the industry, with more than 130 ongoing clinical trials. There are approximately 30 ongoing company-sponsored trials, 14 of which are in Phase 3, and more than 100 investigator-sponsored trials and external collaborations that are active around the world. To date, more than 135,000 patients around the world have been treated with IMBRUVICA in clinical practice and clinical trials.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hemorrhage: Fatal bleeding events have occurred in patients treated with IMBRUVICA. Grade 3 or higher bleeding events (intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, and post-procedural hemorrhage) have occurred in 3% of patients, with fatalities occurring in 0.3% of 1,011 patients exposed to IMBRUVICA in clinical trials. Bleeding events of any grade, including bruising and petechiae, occurred in 44% of patients treated with IMBRUVICA.

The mechanism for the bleeding events is not well understood.

IMBRUVICA may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and patients should be monitored for signs of bleeding.

Consider the benefit-risk of withholding IMBRUVICA for at least 3 to 7 days pre and post-surgery depending upon the type of surgery and the risk of bleeding.

Infections: Fatal and non-fatal infections (including bacterial, viral, or fungal) have occurred with IMBRUVICA therapy. Grade 3 or greater infections occurred in 24% of 1,011 patients exposed to IMBRUVICA in clinical trials. Cases of progressive multifocal leukoencephalopathy (PML) and Pneumocystis jirovecii pneumonia (PJP) have occurred in patients treated with IMBRUVICA. Consider prophylaxis according to standard of care in patients who are at increased risk for opportunistic infections.

Monitor and evaluate patients for fever and infections and treat appropriately.

Cytopenias: Treatment-emergent Grade 3 or 4 cytopenias including neutropenia (23%), thrombocytopenia (8%), and anemia (3%) based on laboratory measurements occurred in patients with B-cell malignancies treated with single agent IMBRUVICA.

Monitor complete blood counts monthly.

Cardiac Arrhythmias: Fatal and serious cardiac arrhythmias have occurred with IMBRUVICA therapy. Grade 3 or greater ventricular tachyarrhythmias occurred in 0.2% of patients, and Grade 3 or greater atrial fibrillation and atrial flutter occurred in 4% of 1,011 patients exposed to IMBRUVICA in clinical trials. These events have occurred particularly in patients with cardiac risk factors, hypertension, acute infections, and a previous history of cardiac arrhythmias.

Periodically monitor patients clinically for cardiac arrhythmias. Obtain an ECG for patients who develop arrhythmic symptoms (e.g., palpitations, lightheadedness, syncope, chest pain) or new onset dyspnea. Manage cardiac arrhythmias appropriately, and if it persists, consider the risks and benefits of IMBRUVICA treatment and follow dose modification guidelines.

Hypertension: Hypertension has occurred in 12% of 1,011 patients treated with IMBRUVICA in clinical trials with a median time to onset of 5 months (range, 0.03 to 22 months). Monitor patients for new onset hypertension or hypertension that is not adequately controlled after starting IMBRUVICA. Adjust existing anti-hypertensive medications and/or initiate anti-hypertensive treatment as appropriate.

Second Primary Malignancies: Other malignancies (9%) including non-skin carcinomas (2%) have occurred in 1,011 patients treated with IMBRUVICA in clinical trials. The most frequent second primary malignancy was non-melanoma skin cancer (6%).

Tumor Lysis Syndrome: Tumor lysis syndrome has been infrequently reported with IMBRUVICA therapy. Assess the baseline risk (e.g., high tumor burden) and take appropriate precautions.

Monitor patients closely and treat as appropriate.

Embryo-Fetal Toxicity: Based on findings in animals, IMBRUVICA can cause fetal harm when administered to a pregnant woman. Advise women to avoid becoming pregnant while taking IMBRUVICA and for 1 month after cessation of therapy. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus. Advise men to avoid fathering a child during the same time period.

ADVERSE REACTIONS

B-cell malignancies: The most common adverse reactions (≥20%) in patients with B-cell malignancies (MCL, CLL/SLL, WM and MZL) were thrombocytopenia (58%)*, neutropenia (58%)*, diarrhea (42%), anemia (39%)*, rash (31%), musculoskeletal pain (31%), bruising (31%), nausea (28%), fatigue (27%), hemorrhage (23%), and pyrexia (20%).

The most common Grade 3 or 4 adverse reactions (≥5%) in patients with B-cell malignancies (MCL, CLL/SLL, WM and MZL) were neutropenia (36%)*, thrombocytopenia (15%)*, and pneumonia (10%).

Approximately 6% (CLL/SLL), 14% (MCL), 14% (WM) and 10% (MZL) of patients had a dose reduction due to adverse reactions. Approximately 4%-10% (CLL/SLL), 9% (MCL), and 7% (WM [5%] and MZL [13%]) of patients discontinued due to adverse reactions.

cGVHD: The most common adverse reactions (≥20%) in patients with cGVHD were fatigue (57%), bruising (40%), diarrhea (36%), thrombocytopenia (33%)*, stomatitis (29%), muscle spasms (29%), nausea (26%), hemorrhage (26%), anemia (24%)*, and pneumonia (21%).

The most common Grade 3 or 4 adverse reactions (≥5%) reported in patients with cGVHD were fatigue (12%), diarrhea (10%), neutropenia (10%)*, pneumonia (10%), sepsis (10%), hypokalemia (7%), headache (5%), musculoskeletal pain (5%), and pyrexia (5%).

Twenty-four percent of patients receiving IMBRUVICA in the cGVHD trial discontinued treatment due to adverse reactions. Adverse reactions leading to dose reduction occurred in 26% of patients.

*Treatment-emergent decreases (all grades) were based on laboratory measurements and adverse reactions.

DRUG INTERACTIONS

CYP3A Inhibitors: Dose adjustments may be recommended.

CYP3A Inducers: Avoid coadministration with strong CYP3A inducers.

SPECIFIC POPULATIONS

Hepatic Impairment (based on Child-Pugh criteria): Avoid use of IMBRUVICA in patients with severe baseline hepatic impairment. In patients with mild or moderate impairment, reduce IMBRUVICA dose.

On December 4, 2018 G1 Therapeutics, Inc. (Nasdaq: GTHX), a clinical-stage oncology company, reported preliminary anti-tumor efficacy and myelopreservation data from its randomized, open-label Phase 2 trial evaluating trilaciclib in combination with chemotherapy as a treatment for metastatic triple-negative breast cancer (mTNBC) (Press release, G1 Therapeutics, DEC 4, 2018, View Source [SID1234531965]). These data will be presented on Wednesday, December 5 at a poster discussion Spotlight Session at the 2018 San Antonio Breast Cancer Symposium (SABCS), being held in San Antonio, Texas.

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The poster is now available on the Publications page of the company’s website.

"In settings such as metastatic triple-negative breast cancer where chemotherapy is dosed until disease progression, trilaciclib has the potential to deliver both multi-lineage myelopreservation and anti-tumor efficacy benefits to patients," said Raj Malik, M.D., Chief Medical Officer and Senior Vice President, R&D. "In this trial, we observed promising early progression-free survival results favoring trilaciclib, as well as myelopreservation benefits across neutrophils, red blood cells, platelets, and lymphocytes."

Trial Design

This randomized, open-label Phase 2 clinical trial enrolled 102 patients with mTNBC who had received 0-2 prior lines of therapy in the recurrent/metastatic setting. In this three-arm trial, all patients received a chemotherapy regimen of gemcitabine and carboplatin (GC). Patients were randomized to receive GC only or GC plus one of two dosing schedules of trilaciclib: trilaciclib administered on the day of chemotherapy (GC/Tx1) or trilaciclib administered the day prior to and the day of chemotherapy (GC/Tx2).

Key Trial Findings

Preliminary median progression-free survival (PFS) was 5.4 months in the GC arm, 8.8 months in the GC/Tx1 arm (hazard ratio 0.52, p=0.0669) and 7.3 months in the GC/Tx2 arm (hazard ratio 0.49; p=0.0546). A combined analysis of trilaciclib-treated patients showed PFS of 5.4 months for the GC arm and 7.9 months for trilaciclib (hazard ratio 0.50, p=0.0189).

Preliminary objective response rate (ORR) was 29.2% in the GC arm, 43.3% in the GC/Tx1 arm and 36.7% in the GC/Tx2 arm.

PFS and ORR in the control arm were consistent with historical data1.

Overall survival (OS) data is immature. OS and updated PFS and ORR will be reported when available.

J Clin Oncol 32:3840-3847

Patients in both trilaciclib groups remained on therapy for a longer duration of time compared to GC only (median weeks: GC=14.4; GC/Tx1=20.0 weeks; GC/Tx2=19.0 weeks).

On a per-patient basis, the number of patients experiencing myelosuppression events was similar across the three arms. When adjusted for the duration of chemotherapy, the trial demonstrated that patients receiving trilaciclib experienced multi-lineage myelopreservation benefits.

Consistent with previous trilaciclib Phase 2 trials, treatment was well tolerated with no trilaciclib-related serious adverse events reported.

Poster Information

Title: Trilaciclib (T), a CDK4/6 inhibitor, dosed with gemcitabine (G), carboplatin (C) in metastatic triple negative breast cancer (mTNBC) patients: Preliminary phase 2 results

Abstract Number: 1191

Presentation Number: PD1-01

Session Title: Developmental Therapeutics

Date / Time / Location: December 5, 5-7 p.m. CST/6-8 p.m. EST, Stars at Night Ballroom 1&2, Henry B. Gonzalez Convention Center

Presenter: Joyce O’Shaughnessy, M.D. (Texas Oncology-Baylor Charles A. Sammons Cancer Center)

For more information about the 2018 San Antonio Breast Cancer Symposium, please visit View Source

About Trilaciclib

Trilaciclib is a first-in-class myelopreservation therapy designed to improve outcomes of patients who receive chemotherapy by preserving hematopoietic stem and progenitor cell (HSPC) and immune system function. Trilaciclib is a short-acting intravenous CDK4/6 inhibitor administered prior to chemotherapy.

Trilaciclib is being evaluated in four randomized Phase 2 clinical trials. G1 has reported positive results from three of these trials in 2018. Two trials showed myelopreservation benefits in newly diagnosed, treatment-naive SCLC patients. In the first trial, trilaciclib was administered in combination with a chemotherapy regimen of etoposide and carboplatin (NCT02499770); topline data were released in March and additional data were reported at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress. In the second trial, trilaciclib was administered in combination with the same chemotherapy regimen and the checkpoint inhibitor Tecentriq (atezolizumab) (NCT03041311); topline data were reported in November. Results from a trial in combination with chemotherapy in metastatic triple-negative breast cancer (NCT02978716) showing enhanced progression-free survival and multi-lineage myelopreservation benefits are being presented at the San Antonio Breast Cancer Symposium on December 5, 2018. The company plans to release topline data from a trial in combination with chemotherapy in previously treated SCLC (NCT02514447) by the end of 2018.

On December 2, 2018 Sunesis Pharmaceuticals, Inc. (Nasdaq:SNSS) reported the presentation of results from the Company’s Phase 1b/2 clinical trial of its non-covalent BTK inhibitor vecabrutinib in adults with relapsed/refractory chronic lymphocytic leukemia (CLL) and other B-cell malignancies (Press release, Sunesis, DEC 3, 2018, View Source [SID1234531815]). The results will be presented today, December 2, from 6:00-8:00 p.m. PT in a poster session titled "CLL: Therapy, excluding Transplantation: Poster II" at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego, California. The poster, titled "Preliminary Safety, Pharmacokinetic, and Pharmacodynamic Results from a Phase 1b/2 Dose-Escalation and Cohort-Expansion Study of the Noncovalent, Reversible Bruton’s Tyrosine Kinase Inhibitor, Vecabrutinib, in B-Lymphoid Malignancy Patients with Prior BTKi Therapy," Abstract No. 3141, is available at www.sunesis.com.

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"To date, vecabrutinib has demonstrated both an encouraging safety profile and evidence of pharmacodynamic activity in CLL and other B cell cancer patients both with and without the BTK C481 mutation," said Dayton Misfeldt, Sunesis interim Chief Executive Officer. "We believe vecabrutinib has significant potential to be an important new treatment for ibrutinib-resistant B-cell malignancy patients, and its additional activity as an ITK inhibitor suggests further directions for clinical investigation. We look forward to continuing the dose escalation, as we believe that the target dose level is likely to be between 100 mg and 300 mg BID. We are excited to be working with such thoughtful and diligent investigators at eight premier sites across the U.S., and we thank our investigators for their continued support."

Data reported today were available from 11 of 13 treated patients. These included 7 with relapsed/refractory CLL, two with mantle cell lymphoma (MCL), and two with Waldenstrom macroglobulinemia (WM). Patients had received an average of 5 lines of prior therapy, and all had progressed on prior covalent BTK inhibitor treatment. Four of the 7 CLL patients had BTK C481 mutations. Currently, 4 patients are on study: one in Cycle 2, one in Cycle 3, and two new subjects who are in Cycle 1 and are anticipated to complete the 50 mg cohort.

The poster builds vecabrutinib’s profile in three key areas:

Safety: data on treatment-emergent adverse events (TEAEs) were available for 10 patients. The most common TEAEs of any grade were anemia (70%) and neutropenia and night sweats (50% each). Grade 3 drug-related AEs were anemia, neutropenia,

leukocytosis, and ALT increase (10% each). In the second cohort, one patient experienced a dose-limiting toxicity of an inadequate number of Cycle 1 doses administered due to a drug-related grade 3 ALT elevation, resulting in expansion of the cohort to 6 patients.

Pharmacokinetics: the pharmacokinetic profile of the 50mg dose is approximately dose proportional to the 25 mg dose. The next dose levels are expected to produce plasma concentrations associated with consistently high inhibition of BTK.

Pharmacodynamics: vecabrutinib inhibition of BTK phosphorylation was rapid and sustained in the 5 patients who had adequate baseline signal for analysis. Decreases in serum concentrations of key cytokines associated with B-cell malignancies, CCL2, CCL3, and CCL4, were also observed in 7 patients, consistent with inhibition of BTK signaling.

Webcast Information

The data will be further discussed as part of an analyst and investor event being held in San Diego today, December 2, at 8:00 p.m. PT, with the slide webcast commencing at 8:30 p.m. PT. The event is intended for institutional investors and sell-side analysts only. Please contact [email protected] for more information. The live webcast of the event, with slides, will be available to all on the Investors section of the Sunesis website at www.sunesis.com and will be archived for 90 days.

About Vecabrutinib

Vecabrutinib (SNS-062) is a selective, oral, reversible, non-covalent inhibitor of Bruton’s tyrosine kinase (BTK). BTK is a validated target for the treatment of B-cell malignancies driven by B-cell receptor signaling. Vecabrutinib retains its activity in the presence of a BTK C481S mutation, the most common mutation seen in ibrutinib-resistant CLL patients. In preclinical studies, vecabrutinib demonstrated potent activity in both wild-type and C481S-mutant BTK. Vecabrutinib has also been shown to inhibit a select number of other kinases including IL2-inducible T-cell kinase (ITK), which may improve T cell function. In a Phase 1a randomized, double-blind, placebo-controlled single ascending dose study in healthy volunteers, vecabrutinib demonstrated improved pharmacokinetics over ibrutinib, and sustained inhibition of BTK. Vecabrutinib is now being investigated in a Phase 1b/2 study in patients with relapsed CLL and other B-cell malignancies.

On December 3, 2018 Syndax Pharmaceuticals, Inc. ("Syndax," the "Company" or "we") (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported the presentation of preclinical data from the Company’s Menin-Mixed Lineage Leukemia (MLL) inhibitor program at the 60thAmerican Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego, California (Press release, Syndax, DEC 3, 2018, View Source [SID1234531831]).

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"Acute leukemias characterized by MLL-rearrangements (MLL-r) and nucleophosmin (NPM1) mutations represent areas of high unmet medical need, with 5-year survival rates falling below 50%," said Briggs W. Morrison, M.D., Chief Executive Officer of Syndax. "Data presented on VTP-50469, a Syndax Menin-MLL inhibitor, provides further support for developing this class of molecules for specific, genetically-defined acute leukemias. The robustness and consistency of the accumulated preclinical data seen with our Menin-MLL inhibitors provide support for an anticipated IND filing on our lead compound, SNDX-5613, in the second quarter of 2019."

In an oral presentation at ASH (Free ASH Whitepaper), Hannah Uckelmann, Ph.D., Dana-Farber Cancer Institute, presented new preclinical data demonstrating that NPM1 mutant progenitor cells can act as drivers of leukemic transformation, and that VTP-50469 can block their pathological capacity by disrupting the menin-MLL interaction. In addition, data generated using a mouse PDX model of NPM1 mutant acute myeloid leukemia (AML) demonstrated that single agent treatment with VTP-50469 eradicated pre-leukemic NPM1 mutant cells and prevented leukemia development, resulting in a marked survival benefit. These data lend further support to the potential therapeutic utility of menin inhibitors in the setting of NPM1 mutant AML.

Furthermore, during a Scientific Spotlight Session at ASH (Free ASH Whitepaper), Scott Armstrong, M.D., Ph.D., Dana-Farber Cancer Institute, provided an overview of the multiple complexes that influence gene expression in MLL-r leukemias and NPM1 AML. Additional preclinical data generated in his laboratory further substantiate that inhibition of the Menin-MLL interaction can decrease leukemic burden and prolong survival in mouse PDX models of both MLL-r and NPM1 mutant leukemias. These data build on prior encouraging preclinical results presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in April, and further underscore the potential therapeutic utility of menin inhibitors as modulators of critical epigenetic mechanisms in acute human leukemias, including subsets of both acute lymphoblastic leukemia (ALL) and AML.

Oral Presentation:

Title: MLL-Menin Inhibition Reverses Pre-Leukemic Progenitor Self-Renewal Induced By NPM1 Mutations and Prevents AML Development
Presenter: Hannah Uckelmann, Ph.D., Research Fellow at the Dana-Farber Cancer Institute
Publication Number: 546

Scientific Spotlight Session:

Title: Targeting Chromatin Complexes in MLL Rearranged Leukemia
Presenter: Scott Armstrong, M.D., Ph.D., Chairman of the Department of Pediatric Oncology at the Dana-Farber Cancer Institute, Associate Chief of the Division Hematology/Oncology at Boston Children’s Hospital, and the David G. Nathan Professor of Pediatrics at Harvard Medical School

Both presentations are available in the Publications section of the Company’s website, www.syndax.com.

About MLL Rearranged Leukemias

Rearrangements of the MLL gene give rise to an acute leukemia, MLL-r. MLL-r occurs in ~80% of infant acute leukemias and up to 10% of adult acute leukemias. It is associated with a poor prognosis, with less than 50% of infants with MLL-r surviving past 5 years. MLL rearrangements produce fusion proteins that require interaction with a protein called Menin in order to drive leukemic cancer growth. Disruption of the Menin-MLL-r interaction has been shown to halt the growth of MLL-r leukemic cells. MLL-r leukemias are routinely diagnosed through currently available cytogenetic screening techniques in leukemic cells, but there are currently no approved therapies indicated for MLL-r leukemias.

About NPM1c Acute Myeloid Leukemia

NPM1c represents another discrete form of acute myeloid leukemia (AML) distinguished by point mutations in the NPM1 gene that drives the leukemic phenotype. NPM1c is the most common type of cytogenetically normal AML and represents ~30% of all diagnosed AML. This subtype of AML has a poor prognosis, with a 5-year overall survival rate of ~50%. Similar to MLL-r leukemias, NPM1c AML is highly dependent on the expression of specific developmental genes, shown to be negatively impacted by inhibitors of the menin-MLL1 interaction. NPM1c AML is routinely diagnosed through currently available screening techniques in leukemic cells, but there are currently no approved therapies indicated for NPM1c AML.