On June 10, 2022 Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, reported positive initial data from its ongoing Phase 2 APEX clinical trial evaluating the selective KIT D816V inhibitor bezuclastinib in patients with advanced systemic mastocytosis (AdvSM) (Press release, Cogent Biosciences, JUN 10, 2022, View Source [SID1234615864]). The data are being presented today in a poster presentation at the 2022 European Hematology Association (EHA) (Free EHA Whitepaper) Congress in Vienna, Austria.

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"Advanced systemic mastocytosis is a severe, debilitating hematologic disorder and physicians and patients remain in search of more effective and better tolerated treatment options to fight this disease," said Daniel DeAngelo, M.D., Ph.D., Chief of the Division of Leukemia at the Dana-Farber Cancer Institute and APEX clinical trial investigator. "I am very impressed with the early, encouraging results presented today from the APEX study. If results like these can be shown in a larger set of patients with AdvSM, I believe bezuclastinib has the potential to help us take a big step forward in treating systemic mastocytosis patients."

"We are very excited to present initial clinical data from the APEX study of bezuclastinib in advanced systemic mastocytosis," said Andrew Robbins, Chief Executive Officer at Cogent Biosciences. "These results reinforce the hypothesis that a potent, selective KIT D816V inhibitor with limited CNS penetration has the potential to provide meaningful clinical activity to all systemic mastocytosis patients, without the tolerability challenges seen with other available treatment options. Based on these results, we expect to accelerate our timelines and investment and look forward to providing another APEX clinical update by the end of 2022, and to presenting SUMMIT clinical data in non-advanced systemic mastocytosis (NonAdvSM) patients in the first half of 2023."

Data from Ongoing Phase 2 APEX Clinical Trial

APEX is a global, open-label, multi-center, two-part Phase 2 clinical trial in patients with AdvSM evaluating the safety, efficacy, pharmacokinetic, and pharmacodynamic profiles of bezuclastinib. As of the data cutoff date of May 24, 2022, 11 patients had been treated in Part 1 at one of four dose levels

(50 mg BID, 100 mg BID, 200 mg BID or 400 mg QD). The median age of patients at study entry was 70 years (ranging from 48-87 years). Patients were enrolled with the following sub-types: two patients with aggressive systemic mastocytosis (ASM), eight patients with systemic mastocytosis with associated hematologic neoplasm (SM-AHN), and one patient with mast cell leukemia (MCL). Two patients had received prior avapritinib and midostaurin treatment.

Initial Safety Data

As of the cutoff date, May 24, 2022, bezuclastinib was generally well-tolerated at all doses. The majority of adverse events were Grade 1/2 and seen in no more than one patient with one serious adverse event and no Grade 4 events reported. Grade 3 events reported as at least possibly related were anemia (1 patient), neutropenia (1 patient) and hypersensitivity/mediator flare (1 patient). There were no reported cases of periorbital/peripheral edema, cognitive effects or intracranial bleeding events, which have been associated with other KIT inhibitors. As of the cutoff date, all patients remained on study. Subsequently, one SM-AHN patient with chronic myelomonocytic leukemia (CMML) transformed to acute myeloid leukemia (AML) and discontinued participation in the trial.

Initial Clinical Activity Data

As of the data cutoff date of May 24, 2022, all 11 patients treated were evaluated for signs of clinical activity. Eight of 11 patients had been treated for at least two cycles, had available data from bone marrow biopsy, and were evaluated for additional endpoints Cycle 3 Day 1 (C3D1) evaluable.

11/11 patients achieved ≥50% reduction in serum tryptase levels by central assessment

89% median reduction in serum tryptase

Six of these patients achieved reduction to <20 ng/mL

8/8 patients (C3D1 evaluable) achieved ≥50% reduction in bone marrow mast cells by central review

Six of these patients achieved complete clearance of bone marrow mast cell aggregates

8/8 patients (C3D1 evaluable) demonstrated decreases in KIT D816V variant allele fraction (VAF) by droplet digital polymerase chain reaction (ddPCR)

All patients remained on treatment with treatment duration ranging from 0.5 – 4.8 months

Two patients enrolled had previously received and discontinued avapritinib for toxicity reasons (intracranial hemorrhage, thrombocytopenia). Both patients have demonstrated clinical outcomes consistent with the avapritinib-naïve patients, including similar magnitude reductions in serum tryptase.

Bezuclastinib Clinical Development

Based on the favorable initial safety and tolerability profile and clinical activity observed to date in the Phase 2 APEX clinical trial with bezuclastinib for AdvSM, Cogent will continue enrolling patients in Part 1 of APEX to determine a recommended dose for use in Part 2 of the trial. A pre-planned interim analysis is scheduled once approximately 28 patients have received at least two cycles of study treatment in Part 1. Cogent plans to present additional data from APEX by the end of 2022. In addition, Cogent continues to actively enroll patients in SUMMIT, a Phase 2 clinical trial with bezuclastinib for NonAdvSM, and PEAK, a registrational randomized, open-label, global, Phase 3 clinical trial in patients with imatinib-resistant Gastrointestinal Stromal Tumors (GIST). Cogent plans to present initial data from SUMMIT and lead-in data from PEAK in the first half 2023.

Conference Call Information & EHA (Free EHA Whitepaper) poster

Cogent will host a webcast today at 8:00 am ET to discuss today’s APEX results. The webcast will be accessible through the Investors and Media section of Cogent’s website at View Source Following the live webcast, an archived replay will also be available.

The APEX poster to be presented at EHA (Free EHA Whitepaper) is available to registered conference attendees as well as on the Cogent Biosciences website in the Posters and Publications section of www.cogentbio.com/research.

On June 10, 2022 Caribou Biosciences, Inc. (Nasdaq: CRBU), a leading clinical-stage CRISPR genome-editing biopharmaceutical company, reported the presentation of additional initial clinical data from its ANTLER Phase 1 trial for CB-010 in patients with relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL) (Press release, Caribou Biosciences, JUN 10, 2022, View Source [SID1234615862]). Following a single dose at the initial dose level of CB-010, a 100% complete response (CR) rate (6 of 6 patients) was observed as best response. At 6 months following the single dose of CB-010, 40% of patients remained in CR (2 of 5 patients) as of the May 13, 2022 data cutoff date. The data are being presented at the European Hematology Association (EHA) (Free EHA Whitepaper) 2022 Hybrid Congress, being held in Vienna, Austria, June 9-17, 2022.

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"The preliminary safety and efficacy results are promising. All six patients treated with CB-010 at the initial dose level of 40 million CAR-T cells achieved a complete response, and we are now enrolling dose level 2 and look forward to seeing this study mature," said Loretta J. Nastoupil, M.D., associate professor, Department of Lymphoma/Myeloma in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center and the presenting investigator on the ANTLER trial. "CB-010 was generally well-tolerated and the adverse events observed are consistent with autologous or allogeneic CAR-T cell therapies."

Additional data, which was received after the cutoff date of May 13, 2022 and was not included in the EHA (Free EHA Whitepaper) poster, showed the first patient treated in the ANTLER trial remained in CR at their 12-month evaluation.

"We believe the 100% complete response achieved in the ANTLER CB-010 trial is unparalleled for a single, starting dose of cell therapy and represents an important step toward showing the potential of our chRDNA genome-editing platform and pipeline of allogeneic cell therapies," said Rachel Haurwitz, Ph.D., Caribou’s president and chief executive officer. "As the first allogeneic anti-CD19 CAR-T cell therapy in the clinic with a PD-1 knockout, CB-010 is designed to have sustained antitumor activity by limiting premature CAR-T cell exhaustion in patients with r/r B-NHL. As we enroll patients in cohort 2 at dose level 2 of the ANTLER trial, we are grateful for the patients, caregivers, and investigators who have participated in this clinical trial. We continue to advance CB-010, as our goal is to develop an allogeneic cell therapy that may meaningfully rival autologous cell therapies and extend the potential reach of off-the-shelf treatments for patients."

This image is also available at: Patient response rates following treatment with CB-010, single dose at dose level 1, in the ANTLER Phase 1 trial

The EHA (Free EHA Whitepaper) poster presentation includes safety, tolerability, and initial antitumor activity data for CB-010 administered at dose level 1 (40×106 CAR-T cells) to 6 patients with r/r B-NHL who had relapsed after previous treatment with a median of 3 prior therapies (range 2-8).

Following treatment with CB-010, there were no cases of graft versus host disease in the six patients. Grade 3 or 4 treatment emergent adverse events (TEAEs) developed in 5 of 6 patients, see details in accompanying table. Two patients experienced Grade 1 CRS (33%) and one patient experienced Grade 3 ICANS (17%), which was characterized as a dose limiting toxicity (DLT), for which the patient received tocilizumab and steroids and recovered within 39 hours. This patient went on to achieve a CR.

Image of table available at: Treatment emergent adverse events in the ANTLER Phase 1 trial

Based on promising initial safety and efficacy data from cohort 1 at dose level 1 (40×106 CAR-T cells), the ANTLER trial is now enrolling patients in cohort 2 at dose level 2 (80×106 CAR-T cells). Additional data are expected by year end.

Details of the poster presentation at EHA (Free EHA Whitepaper) are as follows:

Title: First-in-human trial of CB-010, a CRISPR-edited allogeneic anti-CD19 CAR-T cell therapy with a PD-1 knock out, in patients with relapsed or refractory B cell non-Hodgkin lymphoma (ANTLER study)

Abstract: 3103

Presenter: Loretta J. Nastoupil, M.D., section chief, new drug development; associate professor, Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center

Date and Time: Friday, June 10, 2022, 16:30 – 17:45 CEST (10:30 – 11:45 am ET)

Session Title: Gene therapy, cellular immunotherapy and vaccination – Clinical

Location: Messe Wien Exhibition & Congress Center, Vienna, Austria

The poster is available on the Presentations page of the Investors section of Caribou’s website.

Caribou will host a webcast conference call today to discuss the data presented at EHA (Free EHA Whitepaper) on the initial ANTLER data for CB-010.

The live webcast and conference call at 8:00 am ET, with an accompanying presentation, will be accessible under Events in the Investors section of the company’s website. To participate in the conference call, dial 1-844-862-9351 (domestic) or 1-929-517-0932 (international) and reference conference ID #4657536. The archived audio webcast will be available on Caribou’s website following the call and will be available for 30 days.

About CB-010

CB-010 is the lead product candidate from Caribou’s allogeneic CAR-T cell therapy platform and is being evaluated in patients with relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL) in the ongoing ANTLER Phase 1 trial. CB-010 is an allogeneic anti-CD19 CAR-T cell therapy engineered using Cas9 CRISPR hybrid RNA-DNA (chRDNA) technology to insert a CD19-specific CAR into the TRAC gene and knock out PD-1 to boost the persistence of antitumor activity. CB-010 is the first allogeneic CAR-T cell therapy in the clinic with a PD-1 knock out. Additional information on the ANTLER trial can be found at View Source using identifier NCT04637763.

About Caribou’s Novel Next-Generation CRISPR Platform

CRISPR genome editing uses easily designed, modular biological tools to make DNA changes in living cells. There are two basic components of Class 2 CRISPR systems: the nuclease protein that cuts DNA and the RNA molecule(s) that guide the nuclease to generate a site-specific, double-stranded break, leading to an edit at the targeted genomic site. CRISPR systems are capable of editing unintended genomic sites, known as off-target editing, which may lead to harmful effects on cellular function and phenotype. In response to this challenge, Caribou has developed CRISPR hybrid RNA-DNA guides (chRDNAs; pronounced "chardonnays") that direct substantially more precise genome editing compared to all-RNA guides. Caribou is deploying the power of its Cas12a chRDNA technology to carry out high efficiency multiple edits, including multiplex gene insertions, to develop CRISPR-edited therapies.

On June 10, 2022 The board of directors of Abbott (NYSE: ABT) reported a quarterly common dividend of 47 cents per share (Press release, Abbott, JUN 10, 2022, View Source [SID1234615861]).

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This marks the 394th consecutive quarterly dividend to be paid by Abbott since 1924. The cash dividend is payable Aug. 15, 2022, to shareholders of record at the close of business on July 15, 2022.

Abbott has increased its dividend payout for 50 consecutive years and is a member of the S&P 500 Dividend Aristocrats Index, which tracks companies that have increased dividends annually for at least 25 consecutive years.

On June 10, 2022 SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a clinical-stage biopharmaceutical company focused on developing life-changing medicines for patients with severe rare diseases and cancer, reported that the Company will host a virtual R&D Day today, Friday, June 10th from 10:00 a.m. to 1:00 p.m. ET (Press release, SpringWorks Therapeutics, JUN 10, 2022, View Source [SID1234615859]).

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SpringWorks’ R&D Day will feature presentations by Saqib Islam, Chief Executive Officer; Badreddin Edris, PhD., Chief Operating Officer; L. Mary Smith, PhD, Chief Development Officer; Bhavesh Ashar, Chief Commercial Officer; Mike Burgess, MBChB, PhD, Head of R&D; and Jim Cassidy, MD, PhD, Chief Medical Officer. The event will also include presentations from two external key opinion leaders: Breelyn Wilky, MD, Director of Sarcoma Medical Oncology at the University of Colorado, Denver (CU Denver) and Neal Rosen, MD, PhD, Director of the Center for Mechanism-Based Therapy and the Enid A. Haupt Chair in Medical Oncology at Memorial Sloan Kettering Cancer Center (MSKCC).

"SpringWorks is at an exciting juncture in terms of data generation, regulatory discussions, and launch preparations. Our goal is to provide the first approved therapy for patients with desmoid tumors in 2023, and we expect to have two approved products with the potential to serve patients across four distinct oncology indications by 2025," said Saqib Islam, Chief Executive Officer of SpringWorks. "We are confident that our strong execution across our R&D programs, our disciplined, rigorous approach to business development, and our focused commercial buildout will drive our success in 2022 and beyond."

Agenda

Introduction and Business Overview (Saqib Islam, Badreddin Edris, PhD)
KOL Presentation: Unmet Need in Desmoid Tumors (Bree Wilky, MD, CU Denver)
Nirogacestat
Clinical Experience in Desmoid Tumors (L. Mary Smith, PhD)
Desmoid Tumor Commercial Opportunity (Bhavesh Ashar)
Additional Expansion Opportunity (Badreddin Edris, PhD)
BCMA Therapy Combination Development (Mike Burgess, MBChB, PhD)
Mirdametinib
NF1-PN (L. Mary Smith, PhD)
Additional Expansion Opportunities (Jim Cassidy, MD, PhD)
Mirdametinib + Lifirafenib: Combination Development (Jim Cassidy, MD, PhD)
KOL Presentation: Introduction to BGB-3245 (Neal Rosen, MD, PhD, MSKCC)
BGB-3245
Initial Clinical Data and Program Update (Jim Cassidy, MD, PhD)
Preclinical
TEAD and EGFR Inhibitor Program Overview (Mike Burgess, MBChB, PhD)
Closing Remarks and Q&A (Saqib Islam)
Webcast and Conference Call Information:
The Company’s R&D Day will be held today, Friday, June 10th, from 10:00 a.m. to 1:00 p.m. ET. The webcast can be accessed here. Participants can also listen to the event by dialing + 1 (844) 946-0285 (domestic) or +1 (602) 585-9676 (international) and providing the conference ID 4453188. A replay will be available on the SpringWorks website for a limited period of time following 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 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.