On December 7, 2023 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported full results from the non-registrational Phase 2 KeyVibe-002 trial evaluating vibostolimab/pembrolizumab, an investigational coformulation of vibostolimab, an anti-TIGIT antibody, and pembrolizumab (KEYTRUDA), Merck’s anti-PD-1 therapy, with or without docetaxel for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progressive disease after treatment with immunotherapy and platinum-doublet chemotherapy (Press release, Merck & Co, DEC 7, 2023, View Source [SID1234638245]). These results are being presented today during a poster session at the 2023 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Immuno-Oncology (I-O) Annual Congress (abstract #121P).

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"This study was designed to evaluate a coformulation of vibostolimab and pembrolizumab in a population of patients who are heavily pre-treated and have progressed following treatment with standard of care therapies, often leaving them with limited treatment options and a poor prognosis"

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Data presented at ESMO (Free ESMO Whitepaper) I-O showed that vibostolimab/pembrolizumab plus docetaxel extended median progression-free survival (PFS) by 2.4 months compared to those treated with docetaxel alone, though the results did not reach statistical significance (5.6 months vs. 3.2 months; HR=0.77 [95% CI, 0.53-1.13]; p=0.0910). Vibostolimab/pembrolizumab alone did not show an improvement in median PFS compared to docetaxel alone (2.7 months vs. 3.2 months; HR=1.40 [95% CI, 0.96-2.02]; p=0.9622).

"This study was designed to evaluate a coformulation of vibostolimab and pembrolizumab in a population of patients who are heavily pre-treated and have progressed following treatment with standard of care therapies, often leaving them with limited treatment options and a poor prognosis," said Dr. Scot Ebbinghaus, vice president, global clinical development, Merck Research Laboratories. "We will leverage our evolving understanding of novel combinations and coformulations to help inform our comprehensive research program evaluating this coformulation across a wide range of tumor types."

Data from key secondary endpoints, including overall survival (OS), overall response rate (ORR) and duration of response (DOR) were also presented. Vibostolimab/pembrolizumab plus docetaxel improved OS compared with docetaxel alone, though these results did not reach statistical significance (HR=0.76 [95% CI, 0.50-1.15]). Vibostolimab/pembrolizumab alone did not show an improvement in OS compared to docetaxel alone (HR=1.05 [95% CI, 0.70-1.58). The median OS for vibostolimab/pembrolizumab plus docetaxel was 10.2 months (95% CI, 8.6-14.9), 7.5 months (95% CI, 5.2-13.4) for vibostolimab/pembrolizumab alone and 8.8 months (95% CI, 6.4-11.1) for docetaxel. The ORR for patients receiving vibostolimab/pembrolizumab plus docetaxel was 29.9% (95% CI, 20.5-40.6), 6.0% (95% CI, 2.0-13.5) for vibostolimab/pembrolizumab alone and 15.3% (95% CI, 8.4-24.7) for docetaxel. Median DOR was 6.5 months (range, 2.1+ to 15.4+ months) for the vibostolimab/pembrolizumab plus docetaxel arm. Median DOR was not reached for the vibostolimab/pembrolizumab arm (range, 2.6+ to 6.2+ months) and for the docetaxel arm (range, 1.6 to 11.1+ months).

The safety profile of vibostolimab/pembrolizumab was consistent with that observed for vibostolimab and pembrolizumab in previously reported studies, with no new safety signals observed. Immune-mediated adverse events and infusion reactions occurred in 29.4% of patients who received vibostolimab/pembrolizumab plus docetaxel, 20.5% of those who received vibostolimab/pembrolizumab alone and 12% of those who received docetaxel alone. There were four treatment-related deaths in the vibostolimab/pembrolizumab plus docetaxel arm of the study, and one in each of the vibostolimab/pembrolizumab and docetaxel only arms. In the vibostolimab/pembrolizumab only arm of the study, there was a lower incidence of treatment-related adverse events (TRAEs) of any grade compared to the docetaxel only arm (60.2% vs. 89.2%), and 96.5% of patients in the vibostolimab/pembrolizumab plus docetaxel arm had TRAEs. The most common severe (grade 3-5) TRAEs in the study were neutropenia (16.5%), anemia (7.1%) and asthenia (4.7%) for treatment with vibostolimab/pembrolizumab plus docetaxel; asthenia (2.4%) and diarrhea (2.4%) for vibostolimab/pembrolizumab alone and neutropenia (14.5%) and anemia (6.0%) for docetaxel alone.

Vibostolimab is Merck’s investigational anti-TIGIT antibody that restores antitumor activity by blocking the TIGIT receptor from binding to its ligands (CD112 and CD155), thereby activating T lymphocytes that help destroy tumor cells. Merck has an extensive clinical development program evaluating the safety and efficacy of the vibostolimab/pembrolizumab coformulation alone and in combination with other agents in over 4,000 patients. Ongoing Phase 3 studies in lung cancer include KeyVibe-003, KeyVibe-006, KeyVibe-007 and KeyVibe-008, as well as KeyVibe-010 in melanoma.

About KeyVibe-002

KeyVibe-002 is a randomized, partially blind Phase 2 trial (ClinicalTrials.gov, NCT04725188) evaluating vibostolimab/pembrolizumab, a coformulation of vibostolimab and pembrolizumab, with or without docetaxel versus placebo plus docetaxel in patients with metastatic NSCLC with progressive disease after treatment with immunotherapy and platinum-doublet chemotherapy. The trial’s primary endpoint is PFS, as assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Key secondary endpoints include OS and ORR, as assessed by BICR per RECIST v1.1. The study enrolled 255 patients who were randomly assigned in three separate study arms (1:1:1) to receive either:

Arm 1 (Blinded): Vibostolimab/pembrolizumab (pembrolizumab 200 mg plus vibostolimab 200 mg/20 mL intravenously [IV] every 3 three weeks [Q3W] until a discontinuation criterion is met or completion of 35 cycles) plus docetaxel (75 mg/m2 IV Q3W until a discontinuation criterion is met or as per approved local label); or
Arm 2 (Open-label): Vibostolimab/pembrolizumab (pembrolizumab 200 mg plus vibostolimab 200 mg/20 mL IV Q3W until a discontinuation criterion is met or completion of 35 cycles); or
Arm 3 (Placebo-blinded): Placebo (saline IV Q3W) plus docetaxel (75 mg/m2 IV Q3W until a discontinuation criterion is met or as per approved local label).
KeyVibe-002, a non-registrational study, was designed with two primary objectives: 1) to evaluate the efficacy of vibostolimab/pembrolizumab alone compared with docetaxel, a standard of care; and 2) in a blinded assessment, evaluate the efficacy of adding vibostolimab/pembrolizumab to docetaxel, compared with docetaxel alone.

About lung cancer

Lung cancer is the leading cause of cancer death worldwide. In 2020 alone, there were more than 2.2 million new cases and approximately 1.8 million deaths from lung cancer globally. Non-small cell lung cancer is the most common type of lung cancer, accounting for about 81% of all cases. In the U.S., the overall five-year survival rate for patients diagnosed with lung cancer is 26.2%, which is a 22% improvement over the last five years. Improved survival rates are due, in part, to advances in diagnostic and surgical procedures, as well as the introduction of new therapies. However, screening, early detection and improving treatment rates remain an important unmet need, as 44% of lung cancer cases are not found until they are advanced. Only 4.5% of people in the U.S. who are eligible were screened for lung cancer in 2022.

On December 7, 2023 MBrace Therapeutics, Inc. ("MBrace"), a clinical-stage biopharmaceutical company devoted to improving the lives of cancer patients through the development of antibody-drug conjugates (ADCs) against novel oncology targets, reported new preclinical data supporting ongoing development for lead investigational ADC therapeutic, MBRC-101, at the San Antonio Breast Cancer Symposium taking place December 5-9, 2023, in San Antonio, Texas (Press release, MBrace Therapeutics, DEC 7, 2023, View Source [SID1234638243]).

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"The data presented today further characterize the safety and activity of MBRC-101 and support its potential to effectively treat various solid tumors, including difficult-to-treat breast cancers," said Isan Chen, M.D., co-founder, president, and chief executive officer at MBrace. "We are advancing our clinical evaluation of MBRC-101 in breast cancer, as well as for patients with other EphA5-expressing solid tumor cancers for whom there is a significant need for targeted treatment options."

MBRC-101 is composed of a humanized anti-EphA5 IgG1 antibody conjugated to monomethyl auristatin E (MMAE). In the data presented today, robust and selective EphA5 expression was detected in greater than 80% of triple-negative breast cancer (TNBC) and greater than 80% of HR+ breast cancer tissue samples. EphA5 expression was not detected in adjacent, non-malignant breast tissue or normal breast.

Additionally, extensive in vitro testing showed that MBRC-101 binds to EphA5 exclusively, is rapidly internalized, and is cytotoxic to cells expressing EphA5. Dramatic preclinical efficacy was observed in vivo, with weekly administration of intravenous MBRC-101 showing dose-dependent, robust, and reproducible anti-tumor activity in patient-derived xenograft murine models of TNBC. In addition, in preclinical models, MBRC-101 was well tolerated at doses ranging from 10 mg/kg to 30 mg/kg. Toxicologic findings were attributed to the MMAE payload and not target-related. The highest non-severely toxic dose (HNSTD) was 10 mg/kg (HED = 3.2 mg/kg). At a dosage of 0.5 mg/kg, the safety margin was approximated at 15-fold based on projected human exposures.

The data presented are the results of research conducted both by MBrace, as well as in the laboratories of MBrace co-founders, Renata Pasqualini, Ph.D., Professor at Rutgers Cancer Institute of New Jersey and Chief of the Division of Cancer Biology at Rutgers New Jersey Medical School; and Wadih Arap, M.D., Ph.D., Professor and Chief of the Division of Hematology/Oncology and Director of the Rutgers Cancer Institute of New Jersey at University Hospital.

Details of the poster presentation are as follows:

Abstract Title: MBRC-101: a novel antibody-drug conjugate (ADC) targeting the membrane-associated tyrosine kinase receptor EphA5 in breast cancer

Presenter: Fernanda Staquicini, Ph.D., Director of Research & Development, MBrace Therapeutics

Presentation ID: P03-18-04

Spotlight Session: Poster Session 3

Session Date and Time: Thursday, December 7, 12:00 PM – 2:00 PM CST

Location: Henry B. Gonzalez Convention Center, San Antonio, Texas

Published Abstract Number: 1580268

The poster is also available on the MBrace Therapeutics website at www.mbractetrx.com.

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 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 December 7, 2023 IngenOx Therapeutics, an Oxford-based biopharmaceutical company, reported that its Chief Medical Officer, Prof. David Kerr had published a review on the use of diagnostic biomarkers to personalise adjuvant therapy for patients with colorectal carcinoma (Press release, IngenOx Therapeutics, DEC 7, 2023, View Source [SID1234638241]).

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The review, titled Personalizing adjuvant therapy for patients with colorectal cancer (View Source) is published in Nature Reviews – Clinical Oncology.

Currently, the standard adjuvant treatment for colorectal cancer (CRC) uses a fluoropyrimidine (5-fluorouracil or capecitabine) as a single agent, or in combination with oxaliplatin, spanning 3 to 6 months. The choice of therapy hinges on conventional histopathological staging procedures, which are considered blunt tools for patient stratification.

In contrast, high precision methods allow patients to be stratified into separate groups for different types of treatment. For example, CRC patients with low risk of disease recurrence and a high chance of cure by surgery, versus those with higher risk of cancer recurrence, who would derive greater benefits from chemotherapy.

To this end, in-depth genetic analyses were performed, leading to the discovery of germline determinants of toxicity from fluoropyrimidines. This allows for the identification of patients at high risk of life-threatening toxicity, enabling dose modulation to improve safety.

Further, the review described the application of artificial intelligence-driven models, trained from digital images of resected tissue, to help stratify cancer patients into distinct prognostic groups. The review also touches on liquid biopsy approaches involving measurements of circulating tumour DNA after surgery which are useful tools to identify patients at high and low risk of tumour recurrence.

The review concludes that the wider adoption of the new diagnostic technologies will better enable personalisation of adjuvant therapy for patients with CRC.

David Kerr, CMO of IngenOx, and Professor of Cancer Medicine at the University of Oxford commented:

"This review points the way forward, harnessing both tissue and blood-based assays to better enable selection of patients for adjuvant chemotherapy following apparently curative surgery – influencing treatment of approximately 1 million new patients per year. This review builds on my 30 year experience of leading the UK’s national adjuvant trials portfolio and associated insights into the biology and natural history of colorectal cancer – truly embracing personalised cancer therapy."

IngenOx Therapeutics is a bio-pharmaceutical company focused on delivering new precision medicine drugs and vaccines to treat the most difficult cancers, often referred to as cold tumours. It is a spinout from the University of Oxford, and is located in the Oxford Science Park, UK. Its pipeline comprises early to late-stage products that work in different ways to activate the immune response against cold tumours, which are generally poorly recognised by the immune system. An exciting proprietary platform technology focusses on precision cancer vaccines that act by targeting the immune response to a novel source of cancer antigens.

On December 7, 2023 FORE Biotherapeutics reported that the Company will be presenting at the 2023 RBC Capital Markets Private Company Conference (Press release, Fore Biotherapeutics, DEC 7, 2023, View Source [SID1234638240]). The virtual presentation will take place on Thursday, December 14, 2023, from 8:00-8:30 a.m. ET. Shawn M. Leland, PharmD, RPh, Interim Chief Executive Officer, and Jeffrey Sacher, Interim Chief Financial Officer, will host and participate in one-on-one meetings. Please contact your RBC Capital Markets salesperson or Argot Partners to schedule one-on-one meetings with the management team.

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On December 7, 2023 FibroBiologics, Inc., a clinical-stage biotechnology company focused on the development of therapeutics and potential cures for chronic diseases using fibroblasts and fibroblast-derived materials, reported that it will hold an Investor Day on December 14, 2023, at 10 a.m. EST (Press release, FibroBiologics, DEC 7, 2023, View Source [SID1234638239]). A live webcast will be accessible here as well as on the FibroBiologics website in the News section.

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The session will be held in connection with FibroBiologics’ registration statement on Form S-1 (File No.: 333-275361) filed with the U.S. Securities and Exchange Commission (SEC) on November 7, 2023, relating to the proposed registration and public listing of the company’s common stock.

While FibroBiologics has filed a registration statement (including a preliminary prospectus, which can be found here) with the SEC for the direct listing to which this communication relates, any potential investor should read the preliminary prospectus in that registration statement and other documents FibroBiologics has filed with the SEC for more complete information about FibroBiologics prior to investing. You may get these documents for free by visiting EDGAR on the SEC web site at www.sec.gov. Alternatively, a copy of the preliminary prospectus may be obtained from FibroBiologics through www.FibroBiologics.com. The registration statement relating to FibroBiologics’ common stock has not yet become effective and the common stock may not be sold nor may offers to buy be accepted prior to the time the registration statement becomes effective. This communication shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.