On June 5, 2024 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported that Robert M. Davis, chairman and chief executive officer, and Dr. Dean Y. Li, executive vice president and president, Merck Research Laboratories, are scheduled to participate in a fireside chat at the Goldman Sachs 45th Annual Global Healthcare Conference on Tuesday, June 11, 2024, at 10:00 a.m. EDT (Press release, Merck & Co, JUN 5, 2024, View Source [SID1234644126]).

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Investors, analysts, members of the media and the general public are invited to listen to a live audio webcast of the presentation at this weblink.

On June 5, 2024 Oricell Therapeutics, a pioneering clinical-stage biopharmaceutical company, reported the two-year long-term follow-up results of OriCAR-017, an open-label Phase I study evaluating GPRC5D-targeted CAR-T therapy in patients with relapsed/refractory multiple myeloma (RRMM), in an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, OriCell Therapeutics, JUN 5, 2024, View Source [SID1234644148]).

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Efficacy & Durability of OriCAR-017 in RRMM Patients
The updated data demonstrates that OriCAR-017 elicits deep and durable responses in RRMM patients as well as a favorable safety profile, including those refractory to anti-CD38 therapies, PIs, IMIDs, and those who have failed BCMA targeting CAR-T treatment. The long-term efficacy and safety follow-up results support OriCAR-017 as a promising therapeutic approach for RRMM. Currently, Oricell is smoothly advancing the clinical development of OriCAR-017 in both China (NCT06182696) and the United States (NCT06271252).

As of January 16, 2024, all ten patients responded well to OriCAR-017, with the last patient having completed a 24-month follow-up. The overall response rate (ORR) was 100.0%, with a stringent complete response rate (sCR) of 80.0% and a very good partial response rate (VGPR) of 20.0%. All patients achieved 100% minimal residual disease negativity (MRD) at day 28, which was further confirmed as 100% negative at the 3-months follow-up. The median duration of response (mDoR) was 10.43 months (95% CI, 5.00-17.00), the median progression-free survival (mPFS) was 11.37 months (95% CI, 5.93-18.00), and the median overall survival (mOS) had not yet been reached (7 patients were still under survival follow-up, 1 patient died due to disease progression, and 2 patients died from COVID-19). In the high-dose group, where 67% of patients were previously treated with BCMA CAR-T, the mDoR was 17.23 months (95% CI, 7.33-NR), and the mPFS was 19.10 months (95% CI, 8.30-NR). Currently, a BCMA CAR-T-treated patient is still in remission (>24 months).

Safety Profile of OriCAR-017 in the Treatment of RRMM
The therapy was well-tolerated, with 9 out of 10 patients (90%) experiencing Grade 1 cytokine release syndrome (CRS) and only 1 patient (10%) experiencing Grade 2 CRS. No Grade 3 or higher CRS was observed. The median time to CRS onset was 2 days (range 1-9 days), with a median duration of 6 days (range 3-9 days). No immune effector cell-associated neurotoxicity syndrome (ICANS) or dose-limiting toxicities (DLTs) were observed. There were no serious adverse events (SAEs) or treatment-related deaths, cerebellar disorders, or delayed infections reported.

Pharmacokinetics (PK) of OriCAR-017 in RRMM Patients
There were no pharmacokinetic differences between dose levels, with a Cmax of 7354.7 copies/μL and an AUC0-28 of 68587 copies•day/μg. At high doses, CAR-T cells were still detectable at 9 months, and after 21 months of follow-up, one patient had CAR-T cell expansion above the lower limit of quantitation (LLOQ). Patients with Tlast ≥ 9 months had a longer PFS compared to those with Tlast < 9 months.

G5 Expression in Response to OriCAR-017 Treatment in RRMM
No correlation was observed between antigen expression and therapeutic efficacy. Baseline data from all patients showed positive GPRC5D expression in bone marrow CD138+ plasma cells (MMPC), while 50% of relapsed patients showed downregulated expression detected by flow cytometry.

OriCAR-017 Demonstrates Significant Potential in Severely Progressed RRMM Patients
It’s worth noting that the study included patients with complex and advanced disease characteristics. Among the ten R/R MM patients, 40% had extramedullary disease (EMD), 50% had undergone one or more BCMA-directed CAR-T treatments, 70% had high-risk cytogenetics, 70% were classified as ECOG 2 score status, and 80% were at International Staging System (ISS) stages II & III. OriCAR-017 demonstrates its potential as a safe and efficacious treatment option for RRMM patients, marking a substantial progress in the fight against multiple myeloma and offering hope to those facing demanding health conditions.

Details for the presentation as below:
Oral Presentation #7511
Title: OriCAR-017, a novel GPRC5D-targeting CAR-T, in patients with relapsed/refractory multiple myeloma: Long term follow-up results of phase 1 study (POLARIS).
Session Type:Rapid Oral Abstract Session
Session Title: Hematologic Malignancies—Plasma Cell Dyscrasia
Link: View Source

About OriCAR-017

OriCAR-017, a chimeric antigen receptor (CAR) T cell therapy targeting GPRC5D, is a groundbreaking innovation in the treatment of relapsed/refractory multiple myeloma (RRMM). Leveraging Oricell Therapeutics’ cutting-edge proprietary technology platforms, OriCAR-017 exhibits clearly differentiated binding avidity, persistence, anti-tumor efficacy and safety profile. OriCAR-017 received IND approval from FDA in Jan 2024 after its approval by NMPA in 2023. Impressive clinical results from the POLARIS study continue to be released.

Currently, Oricell has assembled a skilled team to operate in both the U.S. and China, collaboratively accelerating pipeline development globally.

On June 5, 2024 Model Medicines, a leading human health company specializing in generative AI-driven drug discovery, reported the nomination of preclinical candidate MDL-4101, a novel-acting small molecule inhibitor of bromodomain-containing protein 4 (BRD4), for the treatment of thyroid and other cancers (Press release, Model Medicines, JUN 5, 2024, View Source [SID1234644127]). MDL-4101 demonstrates the company’s commitment to leveraging AI to discover novel therapies for aggressive cancers with high unmet medical needs. In particular, MDL-4101 was discovered and the BRD4 program [4] was launched to overcome the limitations of previous BRD4 therapeutics, which have failed to reach the pharmacy [5].

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The nomination of MDL-4101 resulted from Model Medicines’ proprietary AI-driven drug discovery platform, GALILEO, modeling the epigenetic oncology target BRD4, a promising but difficult therapeutic target. BRD4, a member of the bromodomain and extra-terminal (BET) protein family, has emerged as a highly validated therapeutic target across a wide range of cancers. As a key regulator of oncogene expression, BRD4 has been shown to drive tumorigenesis in multiple solid and hematologic malignancies, including breast cancer, prostate cancer, leukemias, and lymphomas. Despite this broad potential, BRD4 has proven challenging to drug selectively, leading to safety and tolerability issues, and has been labeled as difficult to drug, or undruggable, due to the inability of conventional approaches to yield selective and tolerable inhibitors. To date, no selective BRD4 inhibitor has received regulatory approval, underscoring the urgent need for new modalities to effectively target this high-value protein [6-10].

Model Medicines deployed its proprietary GALILEO platform to discover and design MDL-4101 as a selective BRD4 inhibitor that could overcome the limitations of previous programs. By leveraging machine learning to explore vast chemical space and predict drug-like properties, Model Medicines successfully identified MDL-4101 as a potent, selective, and orally bioavailable BRD4 inhibitor, succeeding where traditional approaches have struggled. MDL-4101 demonstrates BRD4 binding in cell free assay [11] and robust anti-tumor activity in a preclinical model of thyroid cancer (CGTH-W-1)[12], suppressing cell proliferation and metastatic capacity. Additionally, preclinical studies have shown evidence of activity in human glioblastoma, prostate, and testicular cancers.

"The successful nomination of MDL-4101 as our first preclinical oncology candidate is a significant milestone for Model Medicines and underscores the unparalleled ability of our AI platform to solve previously intractable challenges in drug discovery," said Daniel Haders, Ph.D., CEO and founder of Model Medicines. "BRD4 is a target that has long captivated drug hunters due to its central role in cancer, but has evaded their grasp. By leveraging AI to intelligently discover and design compounds with optimal properties, we discovered a molecule in MDL-4101 that potentially unlocks the full potential of BRD4 inhibition. We believe this is just the beginning of what our AI-powered approach can achieve against undruggable targets in oncology and beyond."

Thyroid cancer is the most common endocrine malignancy and the tenth most common cancer in the world, accounting for an estimated 586,000 cases worldwide in 2020 [13]. Thyroid cancer is also the fifth most common cancer type in the US, with 44,000 cases in 2022 [13, 14]. BRD4 is found to be up-regulated across many human thyroid cancers and cancer models [15]. The most common subtypes include the differentiated thyroid cancers papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC), which have good prognosis with early intervention [16]. However, treatment options for more aggressive forms, such as anaplastic thyroid carcinoma (ATC) and subtypes such as squamous cell carcinoma of the thyroid (SCCT), remain limited and challenging. Today’s reported results evaluated MDL-4101 in a BRD4-enriched human thyroid cancer model (CGTH-W-1) that was derived from a sample of metastatic SCCT, which has a five-year survival rate of only 6.4% [17]. SCCT is a very aggressive tumor with a poor prognosis. The most recommended treatment involves surgical resection with adjuvant radiotherapy and chemotherapy despite its poor reported outcomes​ [18]. Thus, there is a high unmet medical need for novel therapeutic interventions.

"The preclinical data for MDL-4101 in human thyroid cancer is highly encouraging and speaks to the immense promise of a selectivBRD4 inhibitor," said Dr. Launa Aspeslet, Senior Scientific & Clinical Advisor to Model Medicines. "By unleashing the untapped potential of BRD4 inhibition, we believe MDL-4101 could represent a transformative advance for patients with thyroid and other BRD4 related cancers who currently face a paucity of effective treatment options. We are excited to rapidly progress MDL-4101 into first-in-human studies, while exploring its potential in other cancers driven by BRD4."

Model Medicines plans to initiate Investigational New Drug (IND) enabling studies for MDL-4101, with the goal of submitting an IND application to the U.S. Food and Drug Administration (FDA) and initiating a Phase 1 clinical trial in patients in the near future.

On June 5, 2024 Pierre Fabre Laboratories reported the filing of an investigational new drug ("IND") application to the U.S. Food and Drug Administration ("FDA") to initiate a first-in-human (FIH) Phase I/II clinical trial with PFL-002/VERT-002 for solid tumors including non-small cell lung cancer (NSCLC) (Press release, Pierre Fabre, JUN 5, 2024, View Source [SID1234644149]).

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The PFL-002/VERT-002 Phase I/II trial is a multi-center, international study aimed to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy of PFL-002/VERT-002 in NSCLC patients with MET alterations, including those acquired as resistance mechanism to other treatments. The FDA will review the application and determine its acceptability.

"We are looking forward to initiating the first-in-human trial of PFL-002/VERT-002 later this year. We are confident that this new drug holds significant promise, as a novel therapeutic option with a differentiated mechanism of action, for patients facing MET-altered solid tumors, including NSCLC" said Francesco Hofmann, Head of Research and Development for Medical Care at Pierre Fabre Laboratories.

About PFL-002/VERT-002

PFL-002/VERT-002 is a monoclonal antibody developed by Vertical Bio, offering a unique and differentiating mechanism of action, acting as a degrader of c-MET, a known disease driver in patients with solid tumors, including non-small cell lung cancer (NSCLC) presenting mutations or amplification of MET. The antibody has been optimized preclinically by Vertical Bio, which has been acquired by Pierre Fabre Laboratories.

Pierre Fabre Laboratories is progressing PFL-002/VERT-002 into clinical development and hope to enroll a first patient in the FIH trial by end 2024.

On June 5, 2024 Mural Oncology plc (Nasdaq: MURA), a clinical-stage immuno-oncology company developing novel, investigational engineered cytokine therapies designed to address areas of unmet need for patients with a variety of cancers, reported that Caroline Loew, Ph.D., CEO, will present at the East Coast IDEAS Investor Conference on June 13 at 9:15 a.m. EST (Press release, Mural Oncology, JUN 5, 2024, View Source;1-investor-meetings-14th-annual-east [SID1234644128]). A webcast will be available at www.threepartadvisors.com/east-coast and ir.muraloncology.com.

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About IDEAS Investor Conferences

The mission of the IDEAS Conferences is to provide independent regional venues for quality companies to present their investment merits to an influential audience of investment professionals. Unlike traditional bank-sponsored events, IDEAS Investor Conferences are "SPONSORED BY INVESTORS. FOR INVESTORS" and for the benefit of regional investment communities. Conference sponsors collectively have more than $200 billion in assets under management and include: 1102 Partners, Adirondack Research and Management, Allianz Global Investors: NFJ Investment Group, Ariel Investments, Aristotle Capital Boston, Ascend Wealth Advisors, Barrow Hanley Mewhinney & Strauss, BMO Global Asset Management, Constitution Research & Management, Inc., Diamond Hill, First Wilshire Securities Management, Inc., Granahan Investment Management, Great Lakes Advisors, Greenbrier Partners Capital Management, LLC, Hodges Capital Management, Ironwood Investment Management, Keeley Teton Advisors, Luther King Capital Management, Marble Harbor Investment Counsel, North Star Investment Management, Perritt Capital Management, Punch & Associates, Shepherd Kaplan Krochuk, Westwood Holdings Group, Inc., and William Harris Investors. The IDEAS Investor Conferences are held annually and are produced by Three Part Advisors, LLC. Additional information about the events can be located at View Source