On June 10, 2022 Vincerx Pharma, Inc. (Nasdaq: VINC), a biopharmaceutical company aspiring to address the unmet medical needs of patients with cancer through paradigm-shifting therapeutics, reported a poster presentation of preclinical and clinical data on VIP152, the Company’s PTEFb/CDK9 inhibitor, at the European Hematology Association (EHA) (Free EHA Whitepaper) 2022 Congress, being held virtually and in Vienna, Austria from June 9-12, 2022 (Press release, Vincerx Pharma, JUN 10, 2022, View Source [SID1234615882]).

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The EHA (Free EHA Whitepaper) poster presents data from a high-grade B-cell lymphoma (HGBL) patient with a treatment-related decrease in circulating tumor TP53 mutation and preclinically demonstrates sensitivity of cells derived from chronic lymphocytic leukemia (CLL) patients relapsed after ibrutinib and venetoclax to VIP152 regardless of their TP53 mutation status. "In a pooled analysis of 57 patients with solid or hematologic malignancies, our findings demonstrate that VIP152 did not prolong the QTc interval, which is indicative of a favorable cardiac safety profile and clearly differentiates CDK9 inhibition from the recently reported cardiac toxicity of MCL1 inhibitors," said Ahmed Hamdy M.D., Chief Executive Officer of Vincerx. "Compared with other CDK9 inhibitors, VIP152 was the most selective CDK9 inhibitor and had the most robust MYC mRNA downregulation. We believe the high selectivity of VIP152 affords a manageable safety profile, based on the overall patient safety data we shared earlier this week. Additionally, our data showed reproducible reductions in MYC, MCL1, and PCNA mRNA in the blood of patients with various types of lymphoma after VIP152 treatment. These data support the utility of a selective CDK9 inhibitor for the treatment of patients with hematologic malignancies," added Dr. Hamdy.

The EHA (Free EHA Whitepaper) poster also shares new data for 5 lymphoma patients: 3 with HGBL, 1 double expressor diffuse large B-cell lymphoma (DLBCL) and 1 CLL patient from 2 ongoing phase 1 trials. The safety, treatment duration, pharmacokinetics (PK), and progressive disease (PD) were pooled with 7 previously reported HGBL patients for a total of 12 lymphoma patients shown in the presentation. "Two patients with double-hit DLBCL achieved complete remission for 3.5 and 2.5 years and have remained in remission nearly two years after stopping therapy. In addition, the first patient with CLL—who had failed BTK inhibitors and venetoclax—to be treated with a low dose (15 mg) of VIP152 showed initial evidence of clinical activity by physical exam and laboratory parameters," added Dr. Hamdy. "VIP152 also showed a favorable safety profile in lymphoma patients, with manageable neutropenia. The once-weekly VIP152 dosing regimen continues to allow for recovery of neutrophils before the next dose. The results presented at EHA (Free EHA Whitepaper), combined with the totality of preclinical and clinical data generated in our programs to date, support our recent strategic decision to prioritize our VIP152 clinical program on double-hit DLBCL and CLL. We continue to be excited about VIP152 and look forward to advancing our development program with the goal of delivering new treatment options for these patients."

Key Presentation Highlights:

Poster presentation, titled, "VIP152 is a novel CDK9 inhibitor with improved selectivity, target modulation, and cardiac safety in patients with lymphoma," presented by Melanie Frigault, Ph.D., Vice President of Translational Medicine, Vincerx, include:

A KINOMEscan assay revealed a range of ‘hits’ with VIP152 compared with other CDK9 inhibitors (fadraciclib, alvocidib, KB-0742, and AZD4573). In depth evaluation of all potential hits was performed by Kd determination. Kd values showed VIP152 as the most selective CDK9 inhibitor in the clinic today. In the presence of low ATP, VIP152 has an IC50 value of 4.5 nM, and low nanomolar potency was also maintained in the presence of high ATP. The VIP152 IC50 of 4.5 nM was maintained for 15 to 20 hours in the plasma of patients treated at the current clinical dose of 30 mg. Therefore, VIP152 is a highly potent inhibitor of CDK9 kinase activity even in the presence of high ATP concentrations. These data show that physiologically relevant levels of VIP152 are achieved in patients with the 30-mg dose.
In vitro VIP152 treatment led to the most robust downregulation of MYC mRNA expression, observed by a downregulation of 85% genes in two DLBCL cell lines, SU-DHL-4 and SU-DHL-10, compared with atuveciclib (76%) and KB-0742 (68%).
Pooled cardiac safety data from 57 patients demonstrated that VIP152 does not prolong QTc interval after single or multiple doses (5-30 mg).
VIP152 cytotoxicity was evaluated in CRISPR/Cas9 edited CLL cells with homozygous TP53 mutations and showed that wild type and TP53 mutant cell lines were sensitive to VIP152 treatment at 0.5 and 1.0 µM. In vitro treatment of CLL patient-derived cells showed a concentration-dependent reduction in cell viability regardless of number of lines of prior therapy including cells from patients who had relapsed or were refractory to ibrutinib or venetoclax therapy.
This presentation includes new data from five patients (n=3 with HGBL, n=1 double-hit DLBCL, and n=1 CLL). The safety, treatment duration, pharmacokinetics (PK), and progressive disease (PD) were pooled with 7 previously reported HGBL patients for a total of 12 lymphoma patients shown in the presentation. Duration of treatment for this cohort ranges from 2 weeks to over 3 years. Of the 12 total treated patients, five were evaluable for best overall response. Of these, two patients with double-hit DLBCL achieved complete remission and remain in remission nearly two years after stopping therapy, while others stopped treatment due to clinical or radiographic progression; and, in one case due to investigator decision.
The absolute neutrophil count was measured at each treatment visit. Our data show that once weekly dosing of VIP152 allows for the recovery of neutrophils before the next dose. Neutropenia was considered monitorable and manageable with supportive care.
Blood-based PD effect showed a robust down-modulation of MYC, MCL1 and PCNA mRNA in all 11 patients analyzed. Circulating tumor DNA (ctDNA) changes were monitored in three newly reported patients. In one patient, ctDNA reduction in TP53 mutation, and in CDK6 and MYC copy number was observed after three weeks of VIP152 treatment. ctDNA is currently being investigated as a non-invasive tool to aid with predicting outcomes to treatment in patients with high-risk B-cell lymphoma (Meriranta Blood 2022).
Clinical evaluation of VIP152 is currently ongoing in two phase 1 trials in patients with solid tumors or aggressive NHL (NCT02635672), and with CLL and Richter Syndrome (NCT04978779). The poster can be accessed on the presentations section of the Vincerx website.

On June 10, 2022 Amgen (NASDAQ:AMGN) reported that it will present at the Goldman Sachs 43rd Annual Healthcare Conference at 1:40 p.m. ET on Wednesday, June 15, 2022 (Press release, Amgen, JUN 10, 2022, View Source [SID1234615900]). David M. Reese, M.D., executive vice president of Research and Development and Peter H. Griffith, executive vice president and chief financial officer at Amgen will present at the conference. The webcast will be broadcast over the internet simultaneously and will be available to members of the news media, investors and the general public.

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The webcast, as with other selected presentations regarding developments in Amgen’s business given by management at certain investor and medical conferences, can be found on Amgen’s website, www.amgen.com, under Investors. Information regarding presentation times, webcast availability and webcast links are noted on Amgen’s Investor Relations Events Calendar. The webcast will be archived and available for replay for at least 90 days after the event.

On June 10, 2022 Imago BioSciences, Inc. ("Imago" or the "company") (Nasdaq: IMGO), a clinical stage biopharmaceutical company discovering and developing new medicines for the treatment of myeloproliferative neoplasms (MPNs) and other bone marrow diseases, reported that updated positive data from its ongoing global Phase 2 clinical study evaluating bomedemstat in patients with essential thrombocythemia (ET) (Press release, Imago BioSciences, JUN 10, 2022, View Source [SID1234615857]).

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The data were presented in a poster session during the 30th European Hematology Association (EHA) (Free EHA Whitepaper) Annual Meeting and Congress (EHA) (Free EHA Whitepaper) taking place 9-12 June 2022. A Phase 2 data set with a cut-off of 1 November 2021 was previously presented at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in December 2021.

Updated Highlights (available data as of 29 April 2022):

Enrollment completed with 73 patients in April 2022
Of the 32 patients treated with bomedemstat for more than 24 weeks:
97% (31/32) achieved platelet count reduction to ≤400 x 109/L.
94% (30/32) achieved platelet count reduction to ≤400 x 109/L with no thromboembolic events, the primary efficacy endpoint of this study.
81% (26/32) of patients achieved a durable response, defined as platelet count of ≤400 x 109/L for at least 12 weeks.
Of the 31 patients with Total Symptom Score (TSS) data available at 24 weeks:
58% (18/31) showed a decrease in TSS.
32% (10/31) showed improvements ≥10 points, one component of the ELN criteria for response.
Importantly, platelet response rates were similar across all genotypes identified in the study (CALR, JAK2V617F, MPL and triple negative). Additionally, 67% (16/24) patients demonstrated a net decrease in mutation allele frequencies including both CALR and JAK2.
"I am genuinely thrilled with the results of our ongoing Phase 2 clinical study of bomedemstat in essential thrombocythemia (ET) that continues to support the tremendous potential of our drug candidate. Based on the most recent data cutoff for this Phase 2 trial, as monotherapy in patients with ET who have failed a standard-of-care treatment, bomedemstat demonstrated both favorable platelet and white count reduction and sustained durability of treatment effects," said Hugh Young Rienhoff, Jr. MD, CEO of Imago. "Having now completed, indeed exceeded, our target enrollment in the study, we remain on track for an End-of-Phase 2 meeting with the FDA later this year. Based on our clinical results to date and our productive interactions with regulatory authorities, we are excited about the upcoming Phase 3 registrational trial."

Safety & Tolerability

Bomedemstat was generally well-tolerated with no safety signals identified per the Safety Advisory Board.
The most common adverse events (AEs) (>20%) regardless of causality were dysgeusia (altered taste), fatigue, constipation, and arthralgia.
There were 19 reported serious adverse events (SAEs), 6 of which were deemed drug-related by the Investigator in 5% (3/67) of patients.
14 patients have discontinued treatment, with 10 due to AEs (1 death from aspiration pneumonia unrelated to bomedemstat), 2 due to withdrawal of consent, and 2 due to investigator decision.
Details on the Imago EHA (Free EHA Whitepaper) Presentation

Oral Presentation Title: A Phase 2 Study of the LSD1 Inhibitor IMG-7289 (Bomedemstat) for the Treatment of Essential Thrombocythemia (ET)
Session: 16. Myeloproliferative neoplasms – Clinical
Presenter: Francesca Palandri, M.D., Ph.D., Institute of Hematology "L. & A. Seràgnoli" Sant’Orsola-Malpighi University Hospital, Bologna, Italy
Date & Time: Friday, June 10, 2022, at 10:30 AM ET

For further details, please see the EHA (Free EHA Whitepaper) 2022 abstract and presentation on the Imago website here.

Virtual Investor Event Details

Individuals interested in listening to the event at 10:30 a.m. ET on Saturday, 11 June 2022 may do so by dialing (844) 348-6880 for domestic callers, or +1 (914) 800-3944 for international callers, and reference conference ID: 3493998; or from the webcast link in the investor relations section of the company’s website at: www.imagobio.com. The webcast will be available in the investor relations section on the company’s website for 90 days following the completion of the call.

About Imago’s Phase 2 Essential Thrombocythemia Program

Essential thrombocythemia (ET) is a rare blood cancer resulting in the overproduction of platelets which increases the risk of blood clots and bleeding. It is one of the myeloproliferative neoplasms (MPN) family of rare bone marrow diseases and affects approximately 80,000 – 100,000 patients in the U.S. Imago BioSciences is developing bomedemstat (IMG-7289), an orally administered LSD1 inhibitor, as a potential therapy for patients with ET.

This Phase 2 multi-center, open-label study was designed to assess the safety, efficacy, and pharmacodynamics of bomedemstat, an oral inhibitor of lysine-specific demethylase 1 (LSD1) (www.clinicaltrials.gov Identifier NCT04254978). Eligible patients aged 18 or older with ET who had failed at least one standard therapy and required treatment in order to lower their platelet count were considered for participation in this study. Exploratory assessments include the serial measurement of mutant allele frequencies and changing plasma cytokine profiles. The trial is being conducted in the United States, the United Kingdom, Europe, Hong Kong, New Zealand, and Australia. Imago announced first patient dosed on October 1, 2020. As of April 29, 2022, the trial completed enrollment with 73 participants.

On June 10, 2022 Wugen, Inc., a clinical-stage biotechnology company developing a pipeline of off-the-shelf cell therapies to treat a broad range of hematological and solid tumor malignancies, reported that new preclinical data demonstrating the enhanced anti-tumor properties of WU-NK-101, Wugen’s lead memory natural killer (NK) cell therapy product (Press release, Wugen, JUN 10, 2022, View Source [SID1234615883]). The data elucidate the unique cytokine-induced memory-like (CIML) phenotype of WU-NK-101 and further support its clinical development for acute myeloid leukemia (AML) and a range of solid tumor indications. The findings will be presented during a poster session at the European Hematology Association (EHA) (Free EHA Whitepaper) 2022 Hybrid Congress in Vienna.

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"These data are foundational to our approach and confirm our development strategy as we advance WU-NK-101 for both AML and solid tumors," said Dan Kemp, Ph.D., President and Chief Executive Officer of Wugen. "Today’s presentation highlights key functional features of WU-NK-101: its unique CIML phenotype, enhanced metabolic fitness, and persistent cytotoxic activity, which is maintained even within the harsh immunosuppressive tumor microenvironment. Together, these data affirm our conviction in WU-NK-101 as a best-in-class allogeneic NK cell therapy. We are eager to continue development of WU-NK-101 and expect to advance into an initial clinical trial for patients with relapsed or refractory (r/r) AML followed by additional studies in solid tumor indications."

Today’s presentation highlighted the following:

WU-NK-101 cells have a unique CIML phenotype with improved activation, metabolic flexibility, and cytotoxicity compared to conventional natural killer cells (cNK).

In vivo activity of WU-NK-101 was confirmed in an AML THP-1 xenograft model, where both single- and multi-dose regimens effectively reduced tumor burden relative to vehicle controls. The data support a planned clinical trial of WU-NK-101 for patients with r/r AML.

WU-NK-101 also overcomes several limitations associated with NK cell therapy in solid tumors, with key features including enhanced metabolic fitness and adaptability and enhanced functionality in immunosuppressive TME conditions compared to cNK—functional characteristics supporting further development of WU-NK-101 in solid tumor indications.

The details of Wugen’s poster presentation at EHA (Free EHA Whitepaper) are as follows:

Title: WU-NK-101, An Allogeneic Memory NK Cell, for the Treatment of Relapse or Refractory (R/R) Acute Myeloid Leukemia (AML)
Session date and time: Friday, June 10, 2022, from 4:30 – 5:45 p.m. CEST
Abstract Number: P1426
Presenting Author: Jan Davidson-Moncada, M.D., Ph.D., Chief Medical Officer, Wugen

Additional meeting information can be found at www.ehaweb.org/congress.

About WU-NK-101

WU-NK-101 is a novel immunotherapy harnessing the power of memory natural killer (NK) cells to treat liquid and solid tumors. Memory NK cells are hyper-functional, long-lasting immune cells that exhibit enhanced anti-tumor activity and a cytokine-induced memory-like (CIML) phenotype. This rare cell population has a superior phenotype, proliferation capacity, and metabolic fitness that makes it better suited for cancer therapy than other NK cell therapies. Wugen is applying its proprietary MonetaTM platform to advance WU-NK-101 as a commercially scalable, off-the-shelf cell therapy for cancer. WU-NK-101 is currently in development for acute myelogenous leukemia (AML) and solid tumors.

On June 10, 2022 Imago BioSciences, Inc. ("Imago" or the "company") (Nasdaq: IMGO), a clinical stage biopharmaceutical company discovering and developing new medicines for the treatment of myeloproliferative neoplasms (MPNs) and other bone marrow diseases, reported that updated positive data from its ongoing global Phase 2 clinical study evaluating bomedemstat in patients with advanced myelofibrosis (MF) (Press release, Imago BioSciences, JUN 10, 2022, View Source [SID1234615858]).

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The data were presented in a poster session during the 30th European Hematology Association (EHA) (Free EHA Whitepaper) Annual Meeting and Congress (EHA) (Free EHA Whitepaper), taking place 9-12 June 2022. Previously, a Phase 2 data set with a cut-off of 31 October 2021 was presented at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in December 2021.

Updated Highlights (as of 29 April 2022 data cutoff):

Of the evaluable patients at 24 weeks,
55% (28/51) showed a decrease in Total Symptom Score (TSS).
22% (11/51) showed a ≥50% decrease in TSS.
64% (32/50) showed spleen volume reductions.
52% (36/69) of patients had a decrease in mutant allele frequencies (MAFs) including driver mutations (e.g., JAK2) with the greatest reduction in ASXL1, a high molecular risk (HMR) mutation.
90% (37/41) of transfusion-independent patients had stable or improved hemoglobin at Week 12.
85% (50/59) of patients had an improved (19/59) or stable (31/59) bone marrow fibrosis score post-baseline.
No new mutations or transformation to acute myeloid lymphoma (AML) in patients with high risk of progression.
"The potential of bomedemstat to be a unique and differentiated monotherapy for patients living with advanced myelofibrosis is underscored by the data presented at EHA (Free EHA Whitepaper) today," said Hugh Young Rienhoff, Jr., M.D., CEO of Imago. "The data continue to show improvements across multiple hallmarks of disease, such as symptom scores, spleen volume, fibrosis, and anemia, while at the same time demonstrating a favorable safety and tolerability profile relative to the current available therapies. Of particular interest is the effect on patients with ASXL1 mutations, a mutation that confers an increased risk of leukemia. Importantly, these data also point to the potential utility of bomedemstat in other myeloproliferative diseases, such as polycythemia vera and essential thrombocythemia, with similar mutation profiles. Patients in this study will continue to be treated in an extension study while we further explore these patient responses and evaluate the added value of bomedemstat combined with ruxolitinib."

Safety & Tolerability

Bomedemstat was generally safe and well-tolerated in patients with myelofibrosis.
The most common non-hematologic adverse event (AE) related to bomedemstat was dysgeusia (altered taste), which occurred in 36% of patients and dysgeusia led to discontinuation in 1 patient
There were 14 serious adverse events (SAEs) deemed related to bomedemstat per the Investigator
Details on the Imago EHA (Free EHA Whitepaper) Presentation

Poster Presentation Title: A Phase 2 Study of IMG-7289 (Bomedemstat) in Patients With Advanced Myelofibrosis
Session: 16. Myeloproliferative neoplasms – Clinical
Presenter: Harinder Gill, M.D., study investigator and presenter of the data, Department of Medicine, University of Hong Kong, Queen Mary Hospital, Pok Fu Lam, Hong Kong
Date & Time: Friday, June 10, 2022, at 10:30 AM ET

For further details, please see the EHA (Free EHA Whitepaper) 2022 abstract and presentation on the Imago website here.

Virtual Investor Event Details

Individuals interested in listening to the event at 10:30 a.m. ET on Saturday, June 11, 2022 may do so by dialing (844) 348-6880 for domestic callers, or +1 (914) 800-3944 for international callers, and reference conference ID: 3493998; or from the webcast link in the investor relations section of the company’s website at: www.imagobio.com. The webcast will be available in the investor relations section on the company’s website for 90 days following the completion of the call.

About the Imago Phase 2 Advanced Myelofibrosis Program

Myelofibrosis (MF) is a progressive cancer in which the bone marrow is gradually replaced by fibrous, scar-like tissue. There is a significant unmet need for a disease-modifying therapy. The need is greatest in patients with MF whose disease is not adequately managed with current JAK inhibitors, the current standard of care.

This Phase 2 multi-center, open-label study is designed to assess the safety, efficacy, pharmacodynamics, and spleen volume reduction of bomedemstat, an oral inhibitor of lysine-specific demethylase 1 (LSD1). Eligible patients aged 18 or older with MF who were refractory or resistant to, intolerant of, were inadequately controlled by or ineligible for approved therapies were considered for the study. Exploratory assessments include symptom reduction, changes in cytokine profiles, changes in the frequency of mutant alleles and bone marrow fibrosis. The trial was conducted in the United States, the United Kingdom, European Union, Australia, and Hong Kong. This 24-week study completed enrollment in May 2021 with a total of 89 patients.