On May 31, 2024 Novartis reported positive results from the pivotal Phase III ASC4FIRST trial as a late-breaking abstract at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) meeting. Scemblix (asciminib) demonstrated superior major molecular response (MMR) rates at week 48 compared to investigator-selected standard-of-care (SoC) tyrosine kinase inhibitors (TKIs) imatinib, nilotinib, dasatinib and bosutinib, and compared to imatinib alone in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) (Press release, Novartis, MAY 31, 2024, View Source [SID1234643905]). Scemblix also showed a numerical improvement in MMR at week 48 vs. second generation (2G) TKIs (nilotinib, dasatinib and bosutinib)1. Additionally, Scemblix demonstrated a favorable safety and tolerability profile, with fewer adverse events (AEs) and treatment discontinuations vs. both imatinib and 2G TKIs1.

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"Scemblix is the first CML treatment to show significantly better efficacy compared to investigator-selected standard-of-care TKIs," said Prof. Tim Hughes, MD, South Australian Health & Medical Research Institute (SAHMRI). "When you combine superior response with the excellent safety and tolerability profile of Scemblix, we have a very promising potential frontline option for newly diagnosed patients to support them in achieving their treatment goals."

The median follow-up was 16.3 and 15.7 months for Scemblix and investigator-selected SoC TKIs, respectively1. Nearly 20% more patients treated with Scemblix achieved MMR at week 48 vs. investigator-selected SoC TKIs and nearly 30% more patients achieved MMR at week 48 vs. imatinib alone1. Patients treated with Scemblix also achieved deeper rates of molecular responses (MR4 and MR4.5) compared with investigator-selected SoC TKIs and imatinib alone1.

Overalla
Scemblix (n=201)
vs. investigator-selected SoC TKIs (n=204) Imatinib stratumb
Scemblix (n=101)
vs. imatinib (n=102) 2G TKI stratumc
Scemblix (n=100) vs. 2G TKIs (n=102)

Primary endpoints Week 48 MMR rates 67.7% vs. 49.0% 69.3% vs. 40.2% –
Week 48 MMR Treatment difference (95% CI) 18.9%
(9.6%–28.2%) 29.6%
(16.9%–42.2%)
–
Adjusted 1-sided
p-value <.001 <.001 –

Secondary endpointsd Week 48 MMR rates – – 66.0% vs. 57.8%
Week 48 MR4 39% vs. 21% 43% vs. 15% 35% vs. 26%
Week 48 MR4.5 17% vs. 9% 18% vs. 5% 16% vs. 13%
a All patients receiving Scemblix (n=201) or investigator-selected SoC TKIs (n=204). Treatment difference after adjusting for pre-randomization selected TKI and EUTOS long-term survival (ELTS) risk groups at baseline.
b The 203 patients within the pre-randomization-selected imatinib stratum were randomized to receive either Scemblix (n=101) or imatinib (n=102). Treatment difference after adjusting for ELTS risk groups at baseline.
c The 202 patients within the pre-randomization selected 2G TKIs stratum were randomized to receive either Scemblix (n=100) or 2G TKIs (n=102: nilotinib, 48%; dasatinib, 41%; bosutinib, 11%).
d Secondary endpoints were not powered for statistical significance.

In newly diagnosed patients, the safety profile was consistent with previous registration studies with no new safety concerns observed1. Fewer grade ≥3 AEs, dose adjustments to manage AEs, and half the rate of AEs leading to treatment discontinuation were reported for Scemblix vs. both imatinib and 2G TKIs1.

Scemblix Imatinib 2G TKIs
Grade ≥3 AEsa 38% 44% 55%
AEs leading to treatment discontinuationa 5% 11% 10%
AEs leading to dose adjustments/ interruptionsa 30% 39% 53%
a In patients who experienced ≥1 adverse event.

"Patients living with CML need efficacious and well-tolerated treatment options that help them achieve meaningful outcomes as they manage their chronic condition," said Shreeram Aradhye, M.D., President, Development and Chief Medical Officer, Novartis. "The compelling ASC4FIRST data highlight the potential of Scemblix to achieve better results than standard-of-care in newly diagnosed adults, while maintaining a favorable safety and tolerability profile. These results reinforce Scemblix as a proven treatment in Ph+CML-CP, as we continue to build on our 20-year legacy in CML innovation."

"CML is a chronic condition and the side effects of standard-of-care can be challenging for patients. They often affect their daily life and can lead to high rates of treatment switching," said Gerald Clements, CML caregiver, patient advocate and Steering Committee Treasurer at CML Advocates Network. "Effective care that can be tolerated long-term is a key unmet need. By potentially bringing Scemblix to patients when they are first diagnosed, they may have an opportunity to be on a highly effective treatment while also maintaining their day-to-day from the start."

The trial remains ongoing, with the next scheduled analysis at week 96 to evaluate the key secondary endpoint (MMR at week 96) and additional secondary endpoints18.

These results have been submitted to the US Food and Drug Administration (FDA) via the Oncology Center of Excellence Real-Time Oncology Review (RTOR) program and Scemblix has been granted Breakthrough Therapy Designation. They will also be presented as a plenary at the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Congress in June.

About ASC4FIRST Phase III Clinical Trial
ASC4FIRST (NCT04971226) is a Phase III, head-to-head, multi-center, open-label, randomized study of oral Scemblix 80 mg QD vs. investigator-selected first- or second-generation TKIs (imatinib, nilotinib, dasatinib or bosutinib) in 405 adult patients with newly diagnosed Ph+ CML-CP18. The two primary endpoints of the study are to compare efficacy of asciminib vs. investigator-selected SoC TKIs and to compare efficacy vs. that of TKI within the stratum of participants with imatinib as pre-randomization selected TKI, based on proportion of patients that achieve MMR at week 4818.

The study remains ongoing with key secondary endpoints of proportion of patients that achieve MMR at week 96 and a safety endpoint of discontinuation of study treatment due to an AE (TTDAE) by week 9618. The study also assesses additional secondary safety and efficacy endpoints, including MMR, MR4, MR4.5, complete hematological response (CHR) and BCR::ABL1 ≤1% at and by all scheduled data collection time points; duration of and time to first MMR, MR4 and MR4.5; time to treatment failure; event-free survival, failure-free survival, progression-free survival and overall survival18.

About Scemblix (asciminib)
Scemblix is the first CML treatment that works by Specifically Targeting the ABL Myristoyl Pocket (referred to as a STAMP inhibitor in scientific literature)19-21. The current approved CML treatments are TKIs that target the ATP-binding site (ATP-competitive) 21.

Scemblix is approved in more than 70 countries, including the US and the EU, to treat adults with Ph+ CML-CP who have previously been treated with two or more TKIs22-24. In some countries, including the US, Scemblix is also approved in patients with Ph+ CML-CP with the T315I mutation23-25.
Scemblix is an important treatment option for patients who experience resistance and/or intolerance after two prior TKI therapies2-17, and it is being studied across multiple treatment lines for Ph+ CML-CP, both as a monotherapy and in combination.

On May 31, 2024 MBrace Therapeutics, Inc. ("MBrace"), a clinical-stage oncology company developing novel antibody-drug conjugates (ADCs) against solid tumor targets, reported that the Company will be presenting a Trial in Progress (TIP) poster at the upcoming 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, being held from May 31-June 4, 2024, in Chicago, Illinois (Press release, MBrace Therapeutics, MAY 31, 2024, View Source [SID1234643904]).

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The poster will highlight the trial design, dosing regimen and study protocol for the Company’s ongoing Phase 1/1b clinical trial of MBRC-101. This first-in-human, multicenter, open-label study (NCT06014658) is examining the safety and efficacy of MBRC-101 in patients with advanced metastatic solid tumors refractory to standard treatment. The Company expects to report initial clinical data from this trial in the first half of 2025.

MBRC-101 selectively targets the EphA5 receptor tyrosine kinase, a cell surface receptor highly expressed in many commonly occurring cancers. Through its precision targeting of EphA5, a novel mechanism for solid tumor-directed therapy, MBRC-101 offers a potential new treatment modality, particularly for patients with advanced tumors that are non-responsive to prior cancer therapy.

"ADCs are an incredibly promising class of therapeutics with the potential to offer improved efficacy and greater tolerability," said Shiraj Sen, M.D., Ph.D., medical oncologist and director of clinical research at NEXT Oncology – Dallas, and an investigator in the Phase 1/1b study of MBRC-101. "I look forward to seeing the clinical progress for MBRC-101 and the potential impact that this investigational therapy could have for patients with a cancer that isn’t responding to current treatments."

Details of the ASCO (Free ASCO Whitepaper) 2024 presentation are as follows:
Abstract Title: A multi-center, open-label phase 1/1b dose finding, safety, and pharmacokinetic study of MBRC-101, an Anth-EphA5 monomethyl auristatin (MMAE) antibody drug conjugate, in advanced refractory solid tumors
Presenter: Shiraj Sen, M.D., Ph.D., Medical Oncologist and Director of Clinical Research, NEXT Oncology – Dallas
Session Type and Title: Poster Session – Developmental Therapeutics – Molecularly Targeted Agents and Tumor Biology
Session Date and Time: Saturday, June 1, 2024, 9:00 AM-12:00 PM CDT
Poster Bd #: 305b
Abstract Number: TPS3161

About MBRC-101
MBRC-101 is an investigational antibody-drug conjugate (ADC) that uniquely targets the EphA5 receptor tyrosine kinase, which is present in multiple cancers including, but not limited to, breast, non-small cell lung (NSCLC), colorectal, gastric, and pancreatic cancers. MBRC-101 is currently being evaluated in the MBRC-101-001 Phase 1/1b clinical trial, a first-in-human, open-label, multicenter, dose escalation and dose expansion study enrolling patients with advanced metastatic solid tumors refractory to standard-of-care treatment. For more information about the MBRC-101-001 clinical trial and to review patient eligibility criteria visit clinicaltrials.gov (NCT06014658).

On May 31, 2024 Immunocore Holdings plc (Nasdaq: IMCR) ("Immunocore" or the "Company"), a commercial-stage biotechnology company pioneering and delivering transformative immunomodulating medicines to radically improve outcomes for patients with cancer, infectious diseases and autoimmune diseases, reported Phase 1 data with the first off-the-shelf ImmTAC targeting PRAME, brenetafusp (IMC-F106C), in patients with late-line, post-checkpoint cutaneous melanoma (Press release, Immunocore, MAY 31, 2024, View Source [SID1234643903]). Brenetafusp was shown to be well tolerated, in monotherapy and in combination with anti-PD1, and demonstrated durable clinical benefit.

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"Brenetafusp continues to demonstrate promising monotherapy clinical activity in late-line cutaneous melanoma patients who were previously treated with checkpoint therapies," said Dr. Omid Hamid, Chief, Translational Research and Immunotherapy, Co-Director, Melanoma Therapeutics at Cedars-Sinai Cancer at the Angeles Clinic and Research Institute. "The disease control and PFS benefit for these brenetafusp-treated melanoma patients compares favorably to data with other immunotherapies."

"The best measure of brenetafusp monotherapy activity is disease control, which is observed in 56% of checkpoint pre-treated melanoma patients," said David Berman, Head of Research and Development. "We expect brenetafusp PFS to be even higher in first-line based on our analysis of blood T cell fitness. These data points, in conjunction with the significant molecular response and the expected additive benefit of combining with an active anti-PD1, provide confidence for PFS as an endpoint in our ongoing Phase 3 first-line trial."

Phase 1 data in post-checkpoint cutaneous melanoma

As of 18 March 2024, 47 patients have received brenetafusp (IMC-F106C) monotherapy at clinically active target dose levels. All monotherapy treated patients had received prior immune checkpoint inhibitors (100% anti-PD1, 81% anti-CTLA4). PRAME expression was high amongst evaluable patients (median H score of 215). Only 11% of patients had PRAME negative tumors, as measured by immunohistochemistry.

Brenetafusp was well-tolerated, with treatment-related adverse events (TRAEs) that were manageable and consistent with the mechanism of action. The most frequent TRAE reported was Grade 1 or 2 cytokine release syndrome (CRS) and rash; these events occurred predominantly following the initial three doses. There were no Grade 3 or higher CRS TRAEs.

Of the 47 monotherapy patients, 36 had a RECIST evaluable tumor assessment. The disease control rate (DCR), consisting of partial response (PR) and stable disease (SD), was 56% including 4 PR (ORR 11%) and 16 SD (44%). Durable tumor reduction, confirmed by at least one subsequent scan, was observed in 28% of patients and is an attribute of the ImmTAC platform1. Clinical benefit was enriched in the 31 evaluable PRAME positive patients. The DCR in this group was 58% and included all 10 patients (32%) with confirmed tumor reduction.

Both median progression free survival (mPFS) and 6-month overall survival (OS) rates were greater in PRAME positive than in PRAME negative monotherapy patients: 4.2 vs 2.1 months and 95% vs 40%, respectively.

42% of ctDNA-evaluable, PRAME positive monotherapy patients had a molecular response (10/24) and there was a trend for longer PFS and OS in molecular responders. No ctDNA-evaluable PRAME negative patients had ctDNA reduction.

In addition to the monotherapy patients treated with brenetafusp, there were 9 cutaneous melanoma patients who received brenetafusp in combination with an anti-PD1 (pembrolizumab), all of whom had received prior checkpoint inhibitors (100% prior anti-PD1, 89% prior CTLA4). Overall, patients were more heavily pre-treated in the combination cohort compared to monotherapy (median prior lines: 4 vs 2; PD-1 refractory: 67% vs 30%). Brenetafusp in combination with pembrolizumab was well tolerated, with TRAEs that were manageable and consistent with the mechanism of action of both agents. There was one dose-limiting toxicity (transaminitis) reported in one patient with prior history of checkpoint inhibitor induced autoimmune hepatitis.

Of the 7 patients evaluable for efficacy in combination, 4 achieved disease control including 1 ongoing PR (confirmed after the data cut off for the presentation), and 3 of the 4 ctDNA evaluable patients having molecular response.

In 41 gene-expression evaluable monotherapy patients, a gene signature was identified from baseline peripheral blood that was a measure of systemic T cell fitness. Patients with gene signature expression levels greater than or equal to the median had higher clinical benefit including a median PFS of 6 months and DCR of 69%, compared to those with less than the median gene expression levels (2 months and 42%, respectively). Patients with only 1-2 prior lines of therapy had higher T cell fitness gene signature, on average, than those with 3 or more prior lines of therapy.

The advanced cutaneous melanoma data from the ongoing Phase 1/2 trial of brenetafusp will be presented today at 2:45 PM CT / 3:45 PM ET, in the Melanoma/Skin Cancers oral abstract session at the 2024 American Society of Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. The presentation will be accessible in the ‘Events & Presentations’ section of the Investor Relations section of the Company’s website.

PRISM-MEL-301 – First PRAME Phase 3 clinical trial with brenetafusp in first-line advanced cutaneous melanoma

The Company is enrolling patients in a registrational Phase 3 clinical trial with brenetafusp in first-line advanced cutaneous melanoma (CM) with a primary endpoint of progression-free survival (PFS) (NCT06112314). The trial will randomize HLA-A*02:01-positive, first-line advanced CM patients to brenetafusp + nivolumab versus a control arm of either nivolumab or nivolumab + relatlimab, depending on the country where the patient is enrolled.

Under the terms of a clinical trial collaboration and supply agreement, Immunocore will sponsor and fund this registrational Phase 3 clinical trial, and Bristol Myers Squibb will provide nivolumab.

Audio Webcast

Immunocore will host a conference call today, May 31, 2024 at 7:15 PM ET / 6:15 PM CT, to discuss the Phase 1 PRAME expansion data and Phase 3 registrational trial in cutaneous melanoma. The call will also be available via webcast by visiting the Events & Presentations section on Immunocore’s website. A replay of this webcast will be available for 30 days.

Conference Call Details:
U.S. (toll-free): 877-405-1239
International (toll): +1 201-389-0851

On May 31, 2024 Bio-Techne Corporation (NASDAQ: TECH) reported that Kim Kelderman, President and Chief Executive Officer will present at the following investor conferences (Press release, Bio-Techne, MAY 31, 2024, View Source [SID1234643902]):

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William Blair 44th Annual Growth Conference
June 4, 2024
9:20 AM CDT

Jefferies Global Healthcare Conference
June 6, 2024
9:30 AM EDT

Goldman Sachs 45th Annual Global Healthcare Conference
June 11, 2024
9:20 AM EDT

A live webcast of the presentations can be accessed via the IR Calendar page of Bio-Techne’s Investor Relations website at View Source

On May 31, 2024 Bexion Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company developing a new generation of biologic therapy to treat solid tumor cancers and chemotherapy-induced peripheral neuropathy (CIPN), reported that the Company will present at the 2024 Biotechnology Innovation Organization (BIO) International Convention taking place June 3-6, 2024, in San Diego, California (Press release, Bexion, MAY 31, 2024, View Source [SID1234643901]).

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Presentation Details:

Location: Theater 1, Hall A, Exhibition Hall

Session Date and Time: Wednesday, June 5 at 11:15am PT

"We are delighted to participate in the BIO International Convention in San Diego," said Scott Shively, Bexion’s Chief Executive Officer. "Bexion is approaching critical milestones for our mCRC and CIPN clinical programs, and we look forward to sharing the tremendous progress our team has made."

To schedule a meeting at the BIO International Convention with Bexion Pharmaceuticals, please submit a meeting request through the BIO One-on-One Partnering platform. More details are available on the BIO International Convention 2024 website.

About BIO International Convention

The BIO International Convention is the largest and most comprehensive event for biotechnology, representing the full ecosystem of biotech with over 20,000 industry leaders from across the globe. The convention includes innovative programming around the current and future state of biotech including areas like therapeutic frontiers, the business of biotech, regulatory and policy outlooks, and human capital.

About BXQ-350

Bexion’s lead drug candidate is BXQ-350, a first-in-class biologic containing the multifunctional, sphingolipid activator protein, Saposin C, and a phospholipid. BXQ-350 has pre-clinical antitumor effects in vitro and in vivo, particularly in colorectal, brain and other solid tumors. Two Phase 1 clinical trials, one in adults and one in pediatric DIPG patients, demonstrated a strong safety profile for BXQ-350 with evidence of single agent activity across multiple solid tumors. Additionally, other clinical and non-clinical data suggest BXQ-350 has activity in chemotherapy-induced peripheral neuropathy.