On September 26, 2024 Pasithea Therapeutics Corp. (NASDAQ: KTTA) ("Pasithea" or the "Company"), a clinical-stage biotechnology company developing PAS-004, a next-generation macrocyclic MEK inhibitor, for the treatment of neurofibromatosis type 1 (NF1) and other cancer indications, reported safety, tolerability, pharmacokinetic (PK) and preliminary efficacy data from the first 2 cohorts of patients (n=6) in its Phase 1 clinical trial of PAS-004, being conducted at four clinical sites in the United States (Press release, Pasithea Therapeutics, SEP 26, 2024, View Source [SID1234646880]).

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The Phase 1 clinical trial is a multi-center, open-label, dose escalation 3+3 study design to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and preliminary efficacy of PAS-004 in patients with MAPK pathway driven advanced solid tumors with a documented RAS, NF1 or RAF mutation or patients who have failed BRAF/MEK inhibition (NCT06299839).

"We are very pleased to share the PK, safety, and preliminary efficacy data from the 2 mg and 4 mg cohorts in our first-in-human Phase 1 clinical trial of PAS-004. We believe these data demonstrate a PK and safety profile that differentiates PAS-004 as a next-generation MEK inhibitor. We have already achieved significant PAS-004 exposures with a favorable safety profile and have not seen adverse side effects such as rash or GI toxicity, which are typical for MEK inhibitors even at low doses. The long half-life at approximately 70 hours, and the ability to achieve a flat PK curve at steady-state, aim to provide a constant target inhibition while avoiding peak plasma toxicities, which is a unique PK profile among MEK inhibitors used for the treatment of Neurofibromatosis type 1 (NF1)," stated Dr. Tiago Reis Marques, Chief Executive Officer of Pasithea.

"In addition, we are encouraged to see early potential signs of efficacy, with a heavily pre-treated patient with colorectal cancer showing prolonged stable disease. Colorectal cancer is known to not provide a RECIST response when treated with single-agent MEK inhibitors. This patient has a BRAF K601E mutation, a mutational status with no approved therapies. We are encouraged that this patient has been treated continuously into the 6th 28-day dosing cycle with no toxicities or AEs observed. While still early in clinical development, we believe PAS-004 is showing early signs of differentiation, indicating PAS-004 has the potential to outperform current MEK inhibitors in terms of safety, reduced administration frequency, and potentially efficacy. Our goal is to provide a once-daily or less frequent dosing treatment with broader application, not only for NF1 but also for other indications."

At steady-state, drug levels peaked at about 5 hours with a geometric mean maximum concentration (Cmax) of 16.2 and 61.3 ng/mL for the 2 mg and 4 mg dose groups, respectively. The mean elimination half-life was 67.9 hours supporting once-daily or less frequent oral dosing.

"PAS-004 has demonstrated distinct properties that we believe are significant advantages for an oral MEK inhibitor. PAS-004 has a significantly longer half-life compared to early-generation MEK inhibitors, particularly those used for the treatment of NF1, which have half-lives of less than 8 hours. The ability to achieve prolonged plasma exposures, as reflected in stable plasma concentrations at steady state, may potentially allow PAS-004 to achieve efficacious doses with a favorable safety profile," stated Dr. Tiago Reis Marques, Chief Executive Officer of Pasithea.

Safety & Tolerability

No treatment-related adverse events (TRAEs) or dose limiting toxicities (DLTs) observed to date
In the first 2 dosing cohorts (n=6), PAS-004 was shown to be well-tolerated with a favorable safety profile with no drug-related dose interruptions, reductions or discontinuations. There were no drug-related serious AEs (SAE) in any dose arm and no protocol-defined stopping criteria were met. Importantly, at the 2 and 4 mg dose levels no rash or skin toxicity, gastro-intestinal (GI) toxicity, or ocular toxicity have been observed to date.

The study independent Safety Review Committee has completed its safety review of data from the second dose cohort of 4 mg and the Company has initiated cohort 3 dosing at an increased dose of 8 mg in capsules and has filed a protocol amendment to increase dosing schedule.

PAS-004 Demonstrates a Differentiated MEK Inhibitor Profile

Unlike first-generation MEK inhibitors for the treatment of NF1 that require twice-daily dosing (BID) and exhibit short half-lives (<8 hours), PAS-004 has the potential to achieve prolonged target inhibition due to its long half-life of approximately 70 hours with once-daily dosing (QD). The PK profile shows consistent plasma levels at steady-state, as reflected by a low Cmax to Cmin ratio, potentially reducing the risks for Cmax-related toxicity. These findings provide a compelling rationale for the advancement of PAS-004 into clinical trials for both the treatment of cutaneous and plexiform neurofibromas in NF1, cancer and other MAPK-driven opportunities. The company expects to provide additional trial updates on a periodic basis as the trial progresses.

On September 26, 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 it will host a virtual Investor Day today beginning at 10 a.m. ET (Press release, Mural Oncology, SEP 26, 2024, View Source [SID1234646879]). Mural leadership will provide new clinical insight into the trial design, statistical assumptions, and progress of the company’s late-stage trials of nemvaleukin.

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"Mural has the most advanced IL-2 program currently in development and we have made significant progress this year. We have a great deal of conviction around nemvaleukin, which is engineered to unlock the efficacy potential of high dose IL-2 for more patients, and we are pleased to share more details around our study designs and assumptions during today’s Investor Day," said Caroline Loew, Ph.D., CEO of Mural Oncology. "There has also been significant interest in our IL-18 program and we announced today that we plan to submit an IND to the FDA for this program in Q4 2025. Together we believe these programs have the potential to be the next wave of much needed treatment options for cancer patients."

ARTISTRY-7:
ARTISTRY-7 is a potentially registrational phase 3 trial comparing the combination of nemvaleukin and pembrolizumab versus investigator’s choice single agent chemotherapy in heavily pre-treated patients with platinum-resistant ovarian cancer (PROC), with a primary endpoint of overall survival (OS). Secondary endpoints include progression free survival, overall response rate, disease control rate, duration of response, time to response, CA-125 response, and treatment emergent adverse events. This four-arm trial also contains two smaller monotherapy arms to assess contribution of components.

PROC is an area of high unmet need, with few effective treatment options and poor survival. Nemvaleukin for the treatment of PROC has received Food & Drug Administration (FDA) Fast Track Designation.

Enrollment is complete, with a total of 456 patients (versus 448 planned), and approximately 187 patients in each of the two experimental arms.

Futility analyses are complete for both monotherapy arms:
Pembrolizumab (arm 2):

Predetermined analysis criteria were based on Keynote-100 trial, where single agent pembrolizumab was evaluated in 376 patients with PROC with a response rate of 8%.
Futility in this arm of ARTISTRY-7 was defined as fewer than two confirmed complete or partial responses in the first 12 patients enrolled.
This arm was closed to further enrollment for futility in August 2023 after enrolling 27 patients.
Nemvaleukin (arm 3):

Predetermined futility criteria were based on two historical phase 2 trials using different doses and schedules of aldesleukin, an approved high-dose IL-2, that showed consistent response rates of approximately 25%, including some patients with durable complete responses.1
Futility criteria for this nemvaleukin single arm required at least one patient among the first 24 enrolled to achieve an objective response or stable disease for at least three months to continue enrollment.
The nemvaleukin single arm met this threshold to continue and ultimately enrolled 55 patients.
No statistical comparisons will be performed on the pembrolizumab and nemvaleukin monotherapy arms; all analyses of these two arms will be descriptive.

ARTISTRY-7 Overall Survival Expectations and Rationale
Based on benchmarking against prior phase 3 trials in PROC, which had different eligibility criteria regarding the number of prior therapies, and the eligibility criteria of ARTISTRY-7 which allow for up to five prior lines of therapy in the platinum-resistant or refractory setting, protocol assumptions are:

A median Overall Survival (OS) of 10 months for the chemotherapy control arm.
A median OS of 14.3 months for the nemvaleukin plus pembrolizumab experimental arm.
ARTISTRY-7 Events and Statistics:

Protocol specific interim analysis for OS will occur at 75% of OS events (~215 of 286 total OS events).
Cumulative alpha spend at interim analysis is 1-sided, 0.0096.
Maximum hazard ratio for success at the interim analysis is 0.727 (a 27.3% reduction in the risk of death), assuming exactly 215 OS events.
ARTISTRY-7 Timing:

With enrollment complete, the OS events required for interim analysis are estimated to occur by late Q4 2024 or early Q1 2025.
Mural expects the interim analysis data readout to be available in late Q1 or early Q2 2025.
If the hazard ratio meets the bar for success, the study will be declared positive and the company will plan to file a Biologics License Application (BLA) in 2025.
If the target hazard ratio is not met, the company may decide to continue to final analysis at approximately 286 OS events, or it may decide to terminate the study.
ARTISTRY-6, Cohort 2:
ARTISTRY-6 cohort 2 is a potentially registrational single arm study of single agent nemvaleukin in patients with unresectable or metastatic mucosal melanoma. The trial’s primary endpoint is overall response rate evaluated per RECIST 1.1 by an independent central radiology review. Secondary endpoints include duration of response, time to response, disease control rate, progression-free survival, and safety.

Mucosal melanoma is a rare subtype of melanoma with poor prognosis and currently no approved treatment options. Nemvaleukin for the treatment of mucosal melanoma has received both FDA Fast Track Designation and Orphan Drug Designation.

Enrollment in this study is complete with 92 patients enrolled.

ARTISTRY-6, Cohort 2 Response Rate Assumptions and Rationale:
The target response rate is 25%. At this target, the lower bound of the 95% confidence interval will exceed a 15% response rate.

Mural believes that in this rare and highly aggressive tumor with poor outcomes even in the first line setting, demonstrating durable responses with a response rate of 20-25% would be meaningful for patients, and would support a discussion with the FDA regarding a potential BLA submission and potential accelerated approval.

A potential accelerated approval would require confirmatory evidence to be agreed with and later submitted to the FDA for conversion to a regular approval. Discussions with FDA on a potential confirmatory evidence package are ongoing.

ARTISTRY-6 Timing:

The primary analysis will occur when all patients have a minimum follow-up of at least six months. In order to ensure adequate follow-up on all patients, Mural anticipates that the top-line readout will occur in the second quarter of 2025.
Potential accelerated approval with confirmatory evidence to be later submitted for conversion to regular approval.
Regulatory filing may be deferred if the ARTISTRY-7 study continues to final analysis, pending the final outcome.
Mural Oncology’s IL-18 Program:

Mural plans to nominate a development candidate for its IL-18 program by the end of 2024 and intends to submit an Investigational New Drug (IND) Application to the FDA in Q4 2025.

Mural Investor Day Webcast Details:
Mural’s management team will be joined by three clinicians on the webcast to discuss the treatment landscape for PROC and mucosal melanoma, as well as nemvaleukin’s clinical proof of concept data.

The live webcast will begin at 10 a.m. followed by a Question & Answer session. To join the webcast, please visit View Source

A replay of the webcast will be available shortly after the conclusion of the meeting.

On September 26, 2024 INmune Bio Inc. (NASDAQ: INMB) (the "Company"), a clinical-stage immunology and inflammation company, reported to advance its Natural Killer (NK) cell therapy, INKmune, in a Phase I/II trial (the "CaRe PC" trial) for men with metastatic Castration-Resistant Prostate Cancer (mCRPC) (Press release, INmune Bio, SEP 26, 2024, View Source [SID1234646878]). The Company is pleased to announce initial results from the first patient cohort in the trial.

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Mark Lowdell, CSO and inventor of INKmune, said, "The enrollment of the first cohort ran entirely in-line with our predicted timelines and confirmed the excellent safety profile with all patients receiving treatment as out-patient without the need for pre-medication of any kind. Furthermore, even at this lowest dose of INKmune, there is clear evidence of persistent immunologic effects of INKmune treatment in these men with mCRPC.

Blinded analysis of the monitoring blood samples from the first three patients showed changes in the phenotype and function of the patient’s NK cells. Although this is the lowest dose cohort, 2 of 3 patients showed an increase in circulating activated NK cells and all three showed increased NK cell function sustained for more than 40 days after the final INKmune infusion. One patient showed a transient 21% decrease in PSA associated with the increase in NK cell activity and function.

The CaRe PC trial has recently completed dosing the last patients in the second of its three dose-escalation cohorts. The third cohort is expected to begin in approximately 30 days. The dose of INKmune in the second and third cohort is 3 and 5 times the dose of INKmune in the first cohort. All eight clinical sites are now open and additional results from the trial will be released from the higher dose cohorts as they become available.

About INKmune

INKmune is a pharmaceutical-grade, replication-incompetent human tumor cell line which conjugates to resting NK cells and delivers multiple, essential priming signals to convert the cancer patient’s resting NK cells into tumor killing memory-like NK cells (mlNK cells). INKmune treatment converts the patient’s own NK cells into mlNK cells. In patients, INKmune primed tumor killing NK cells have persisted for more than 100 days. These cells function in the hypoxic TME because due to upregulated nutrient receptors and mitochondrial survival proteins. INKmune is a patient friendly drug treatment that does not require pre-medication, conditioning or additional cytokine therapy to be given to the patients. INKmune is easily transported, stored and delivered to the patient by a simple intravenous infusion as an out-patient. INKmune is tumor agnostic; it can be used to treat many types of NK-resistant tumors including leukemia, lymphoma, myeloma, lung, ovarian, breast, renal and nasopharyngeal cancer. INKmune is treating patients in an open label Phase I/II trial in metastatic castration-resistant prostate cancer in the United States.

On September 26, 2024 ImmunoPrecise Antibodies Ltd.(the "Company" or "IPA") (NASDAQ: IPA), ImmunoPrecise Antibodies Ltd. (the "Company" or "IPA") (NASDAQ: IPA), an AI-driven biotherapeutic research and technology company, reported the clinical progress achieved with rabbit monoclonal antibodies designed and developed using IPA’s proprietary B Cell Select platform for the clinical-stage company, OncoResponse Inc (Press release, ImmunoPrecise Antibodies, SEP 26, 2024, View Source [SID1234646877]). This achievement underscores IPA’s leadership as a Contract Research Organization creating high-quality therapeutic antibodies, while pioneering work in the field of rabbit monoclonal antibody development. These antibodies are rapidly gaining recognition as a unique tool in therapies due to their distinctive properties, advancing into clinical trials aimed at improving patient outcomes.

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OncoResponse’s Breakthrough in Cancer Treatment

In a live presentation at the recent PEGS 2024 conference, OncoResponse shared exciting updates on two novel antibodies, OR502 and OR641, both of which were discovered and refined using IPA’s innovative B Cell Select platform:

•
OR502, a novel, humanized anti-leukocyte immunoglobulin like receptor B2 (LILRB2) antibody, has successfully entered Phase I/II clinical trials, showing excellent safety profile, and is being evaluated for efficacy in treating advanced solid tumors. Preclinical models have demonstrated that OR502 is a best-in-class anti-LILRB2 antibody that reverses immunosuppression caused by myeloid cells in the TME.
•
OR641, a novel, humanized dual antagonist antibody targeting both LILRB1 and LILRB2, has completed Cell Line Development and is undergoing IND-enabling studies. Preclinical models have demonstrated its superior ability to reverse immunosuppression caused by myeloid and lymphoid cells compared to other anti-LILRB1/2 antibodies.

Driving Antibody Discovery and Design for Clinical Success

IPA’s proprietary B Cell Select platform has been instrumental in the rapid design and discovery of antibodies that have advanced to clinical stages for numerous clients. By preserving the natural structure of antibodies, IPA’s technology supports optimal functioning of the therapies in a clinical setting. Through comprehensive testing and validation, the process ensures that these antibodies maintain their efficacy and reliability from the lab to the clinic.

"At ImmunoPrecise Antibodies, our mission is not just to develop antibodies, but to redefine what’s possible in therapeutic interventions," said Dr. Jennifer Bath, President and CEO of IPA. "Our innovative platform, built on years of expertise, has consistently delivered antibodies with superior qualities, many of which are now advancing in clinical trials. This reflects our unwavering commitment to innovation and our strategic advantage in the market. We are proud to support our clients in bringing groundbreaking, life-changing treatments to patients around the world, reinforcing the long-term value of our technologies."

Harnessing Rabbit B Cell Technology for Breakthrough Antibody Discovery

The Rabbit B Cell platform, a rapidly advancing technology in therapeutic antibody development, played a pivotal role in the discovery process. This platform excels at generating high-affinity and highly specific rabbit monoclonal antibodies, a demand met with very limited providers in the market.

IPA has successfully utilized their B Cell Select platform in over 200 antibody programs, achieving remarkable success against a variety of targets, including small molecules, peptides, and proteins. The distinctive properties of rabbit antibodies, combined with IPA’s expertise, have consistently led to the development of promising therapeutic candidates. Building on this success, IPA is now offering more complex therapeutic rabbit antibody campaigns as a partnering model, providing companies with greater flexibility in structuring their more complicated programs.

Outlook

The field of rabbit monoclonal antibody (mAb) therapeutics is advancing rapidly, driven by innovations in antibody engineering and humanization techniques. These advancements are making rabbit mAbs increasingly popular for human therapeutic use. The unique properties of rabbit antibodies, combined with IPA’s full-service technologies, such as in silico humanization, indicate a strong potential for more rabbit-derived mAbs to enter clinical trials and achieve approval in the coming years. The distinctive advantages of rabbit antibodies make them a promising foundation for future therapeutic development. As this technology progresses, IPA remains at the forefront, harnessing these innovations to bring new, effective treatments to the clinic, reinforcing our growing leadership in the industry.

Dr. Kamal D. Puri, Chief Scientific Officer of OncoResponse, recognized IPA’s pivotal role in their success, praising the quality and reliability of IPA’s antibody discovery services. "We are thrilled to have worked with IPA to discover our lead therapeutic antibodies. The IPA team’s deep experience and know-how with a battery of customized, high-throughput discovery strategies has played a critical role in the successful discovery of our molecules with unsurpassed speed and efficiency," said Kamal D. Puri, Chief Scientific Officer of OncoResponse.

About OR502

LILRB2 is an immunoinhibitory receptor expressed on tumor-associated macrophages (TAMs) found in the tumor microenvironment (TME). TAMs inhibit the activity of checkpoint inhibitor (CPI) therapy and prevent T cells from killing tumors. Blocking the inhibitory activity of TAMs and promoting the activity of tumor-killing T cells reverses inhibition of CPI therapy, potentially leading to more and deeper responses to CPIs in patients. This is the mechanism of OR502, which modulates LILRB2 by blocking its engagement of HLA-G on tumor cells and prevents the suppression of the myeloid cells. Elevated expression of LILRB2 correlates with reduced patient survival in various tumor types. This humanized monoclonal antibody, OR502, targets LILRB2 and blocks the inhibitory activity of TAMs and promotes the activity of tumor-killing T cells, reversing inhibition of CPI therapy.

On September 26, 2024 GT Biopharma, Inc. (the "Company") (NASDAQ: GTBP), a clinical stage immuno-oncology company focused on developing innovative therapeutics based on the Company’s proprietary natural killer (NK) cell engager TriKE platform, reported that Dr. Jeffrey Miller, MD1, from the University of Minnesota Medical School and GT Biopharma’s Consulting Senior Medical Director, will participate in a panel discussion on innovative therapies for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) at the 3rd Annual ROTH Healthcare Opportunities Conference taking place October 9, 2024 in New York, NY (Press release, GT Biopharma, SEP 26, 2024, View Source [SID1234646876]). Company management will also be participating in 1×1 meetings during the event.

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3rd Annual ROTH Healthcare Opportunities Conference – October 9, 2024
Title: Panel 4 – Focus: Hematologic malignancies
Date: Wednesday, October 9, 2024
Time: 1:15-1:55 pm ET
Participant: Dr. Jeffrey Miller, MD, Deputy Director, Masonic Cancer Center, Co-Leader Immunology Program at the University of Minnesota Medical School & Consulting Senior Medical Director, GT Biopharma

If you are interested in arranging a 1×1 meeting request with management, please contact your ROTH representative.