On May 28, 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 the publication of data showing PAS-004 strongly inhibiting NRAS mutant cancer cell lines with IC50 values ranging from 0.024 to 0.306 µM (Press release, Pasithea Therapeutics, MAY 28, 2024, View Source [SID1234643741]). Maximal growth inhibition of >50% was achieved by PAS-004 in more cell lines than binimetinib and selumetinib. In addition, PAS-004’s cell line inhibition was comparable to trametinib in 5 cell lines tested but, in contrast to trametinib, PAS-004 did not reach a plateau.

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The results will be presented at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 1, 2024, in a poster session from 9:00 am – 12:00 pm CDT in Chicago, IL.​​

"We are excited to show new preclinical data showing enhanced potency of PAS-004 when compared to approved agents, with the potential for less frequent dosing which may lead to better tolerability and compliance." said Dr. Tiago Reis Marques, Chief Executive Officer of Pasithea. "We believe this emerging profile hits the sweet spot balancing pharmacokinetics (PK), pharmacodynamics (PD) and tolerability and making PAS-004 an ideal candidate for the treatment of cutaneous and plexiform NF1 as well as a potential candidate for treatment of various cancers. We are looking forward to the initial readout of our Ph1 clinical trial."

PAS-004 is the first macrocyclic MEK inhibitor to enter human clinical trials, with an expected extended half-life which may provide better compliance rates, as well as improved efficacy in NF1. Macrocycles are known to exhibit stronger binding, better solubility and longer half-life with more selectivity and less off target effect as compared to acyclic small molecules.

Presentation and poster details

Title: PAS-004: A novel macrocyclic MEK inhibitor to inhibit cancer cell growth in vitro and tumor growth in mouse xenograft studies.
Presenting author: Graeme Currie, PhD
Session: Poster Session – Developmental Therapeutics – Molecularly Targeted Agents and Tumor Biology
Date and Time: 6/1/2024, 9:00 AM – 12:00 PM CDT

About PAS-004

PAS-004 is a small molecule allosteric inhibitor of MEK 1/2, which are dual-specificity protein kinases, in the MAPK signaling pathway. The MAPK pathway has been implicated in a variety of diseases, as it functions to drive cell proliferation, differentiation, survival and a variety of other cellular functions that, when abnormally activated, are critical for the formation and progression of tumors, fibrosis and other diseases. MEK inhibitors block phosphorylation (activation) of extracellular signal-regulated kinases (ERK). Blocking the phosphorylation of ERK can lead to cell death and inhibition of tumor growth. Existing FDA approved MEK inhibitors are marketed for a range of diseases, including certain cancers and neurofibromatosis type 1 (NF1). We believe these MEK inhibitors suffer from certain limitations, including known toxicities. Unlike current FDA approved MEK inhibitors, PAS-004 is macrocyclic, which we believe may lead to improved pharmacokinetic and safety (tolerability) profiles. Cyclization offers rigidity for stronger binding with drug target receptors. PAS-004 was designed to provide a longer half-life with what we believe is a better therapeutic window. Further, we believe the potency and safety profile that PAS-004 has demonstrated in preclinical studies may also lead to stronger and more durable response rates and efficacy, as well as better dosing schedules. PAS-004 has been tested in a range of mouse models of various diseases and has completed preclinical testing and animal toxicology studies. Additionally, PAS-004 has received orphan-drug designation from the FDA for the treatment of NF1.

On May 28, 2024 NeoTX Therapeutics (NeoTX), a clinical-stage immuno-oncology drug development company, reported abstract acceptance at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2024 Annual Meeting being held May 31- June 4, 2024, at the McCormick Place, Chicago, IL (Press release, NeoTX, MAY 28, 2024, View Source;utm_medium=rss&utm_campaign=neotx-announces-poster-presentation-at-asco-2024-annual-meeting [SID1234643740]). The poster will present preliminary results of clinical activity and safety of naptumomab estafenatox (NAP) and docetaxel in a phase 2 trial in patients with advanced/ metastatic non-small cell lung cancer (NSCLC) which have been pretreated with standard chemotherapy and a checkpoint inhibitor (CPI). Details on the presentation are as follows:

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Abstract Title:
Clinical Activity and Safety of Naptumomab Estafenatox (NAP) and Docetaxel in Patients (pts) with Checkpoint Inhibitor (CPI) Pre-treated Advanced/ Metastatic Non-Small Cell Lung Cancer (NSCLC) – Preliminary Results, P2 Trial
Abstract Number:
8615
Session Type and Title:
Poster Session – Lung Cancer—Non-Small Cell Metastatic
Session Date & Time:
Monday June 3, 2024, 1:30 PM – 4:30 PM CDT

On May 28, 2024 NANOBIOTIX (Euronext: NANO –– NASDAQ: NBTX – the ‘‘Company’’), a late-clinical stage biotechnology company pioneering nanoparticle-based therapeutic approaches to expand treatment possibilities for patients with cancer and other major diseases, reported the presentation of updated data from the completed dose escalation part and first data from the ongoing expansion part of Study 1100, a US Phase 1 study evaluating NBTXR3 followed by anti-PD-1 in patients with recurrent or metastatic head and neck cancer (n=68) at the 2024 Annual Meeting of the American Society for Clinical Oncology (Press release, Nanobiotix, MAY 28, 2024, View Source [SID1234643739]). The data will be presented by Study 1100 Coordinating Investigator Colette Shen, MD, PhD, during a poster presentation session that begins at 10:00 AM EDT / 4:00 PM CEST on Sunday, June 2nd, 2024.

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ABSTRACT #6035: Early signs of efficacy in patients with anti-PD-1 naïve (n=33) and anti-PD-1 resistant (n=35) HNSCC treated with NBTXR3/SBRT in combination with nivolumab and pembrolizumab in the phase 1 trial Study 1100
Colette Shen1, Jessica Frakes2, Trevor Hackman1, Jiaxin Niu3, Jared Weiss1, Jimmy Caudell2, George Yang2, Tanguy Seiwert4, Paul Chang5, Septimiu Murgu5, Siddharth Sheth1, Shetal Patel1, Kedar Kirtane2, David Rolando6, Pavel Tyan6, Omar I. Vivar6, Zhen Gooi5, Aditya Joolori5, Ari Rosenberg5

Nanobiotix Investor Call

Nanobiotix will host a conference call and webcast featuring Nanobiotix chief executive officer and chairman of the executive board, Laurent Levy, following the poster session on Sunday June 2nd, 2024, at 12:00 PM EDT / 6:00 PM CEST.

Details for the call are as follows:

Audio-only dial-in link: click here

Webcast link: click here

Participants can use the audio-only link above to register and obtain dial-in instructions to listen to the presentation via phone and ask questions during the Q&A session, or participants can use the webcast link to register and listen and watch the slide presentation online; the replay version will be available under the same webcast link shortly after the presentation and will be archived on the Company’s website at www.nanobiotix.com. It is recommended to join 10 minutes prior to the event start. Participants are invited to email their questions in advance to [email protected].

1University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA; 2Moffitt Cancer Center, Tampa, Florida, USA; 3Banner MD Anderson Cancer Center, Gilbert, Arizona, USA; 4Johns Hopkins Medicine, Baltimore, Maryland, USA; 5The University of Chicago, Chicago, Illinois, USA; 6Nanobiotix, SA, Paris, France

About NBTXR3

NBTXR3 is a novel, potentially first-in-class oncology product composed of functionalized hafnium oxide nanoparticles that is administered via one-time intratumoral injection and activated by radiotherapy. Its proof-of-concept was achieved in soft tissue sarcomas for which the product received a European CE mark in 2019. The product candidate’s physical mechanism of action (MoA) is designed to induce significant tumor cell death in the injected tumor when activated by radiotherapy, subsequently triggering adaptive immune response and long-term anti-cancer memory. Given the physical MoA, Nanobiotix believes that NBTXR3 could be scalable across any solid tumor that can be treated with radiotherapy and across any therapeutic combination, particularly immune checkpoint inhibitors.

Radiotherapy-activated NBTXR3 is being evaluated across multiple solid tumor indications as a single agent or in combination with anti-PD-1 immune checkpoint inhibitors, including in NANORAY-312—a global, randomized Phase 3 study in locally advanced head and neck squamous cell cancers. In February 2020, the United States Food and Drug Administration granted regulatory Fast Track designation for the investigation of NBTXR3 activated by radiation therapy, with or without cetuximab, for the treatment of patients with locally advanced HNSCC who are not eligible for platinum-based chemotherapy—the same population being evaluated in the Phase 3 study.

Given the Company’s focus areas, and balanced against the scalable potential of NBTXR3, Nanobiotix has engaged in a collaboration strategy to expand development of the product candidate in parallel with its priority development pathways. Pursuant to this strategy, in 2019 Nanobiotix entered into a broad, comprehensive clinical research collaboration with The University of Texas MD Anderson Cancer Center to sponsor several Phase 1 and Phase 2 studies evaluating NBTXR3 across tumor types and therapeutic combinations. In 2023, Nanobiotix announced a license agreement for the global co-development and commercialization of NBTXR3 with Janssen Pharmaceutica NV.

On May 28, 2024 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported that the Phase 3 KEYNOTE-522 trial evaluating KEYTRUDA, Merck’s anti-PD-1 therapy, met its overall survival (OS) endpoint, in combination with chemotherapy as pre-operative (neoadjuvant) treatment and then continuing as a single agent after surgery (adjuvant) for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) (Press release, Merck & Co, MAY 28, 2024, View Source [SID1234643738]). At a pre-specified interim analysis conducted by an independent Data Monitoring Committee, KEYTRUDA demonstrated a statistically significant and clinically meaningful improvement in OS compared to pre-operative chemotherapy. The safety profile of KEYTRUDA was consistent with that observed in previously reported studies; no new safety signals were observed. Results will be presented at an upcoming medical meeting and shared with regulatory authorities.

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"This is a significant milestone, as it is the first time an immunotherapy-based regimen has demonstrated a statistically significant overall survival benefit compared to chemotherapy alone in patients with high-risk early-stage triple-negative breast cancer," said Dr. Gursel Aktan, vice president, global clinical development, Merck Research Laboratories. "To have achieved overall survival from this landmark study is highly encouraging and builds upon the positive pathological complete response and event-free survival results that led to approvals for this regimen around the world."

KEYNOTE 522 is the fourth study of a KEYTRUDA-based regimen in an earlier stage of cancer to demonstrate an OS benefit, in addition to KEYNOTE-A18 in cervical cancer, KEYNOTE-671 in non-small cell lung cancer and KEYNOTE-564 in renal cell carcinoma.

In the U.S., KEYTRUDA has two approved indications in TNBC: for the treatment of patients with high-risk early-stage TNBC in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery; and in combination with chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.

Merck has a comprehensive clinical development program in various subtypes of breast cancer. This includes KEYNOTE-242 evaluating KEYTRUDA monotherapy as adjuvant treatment in patients with TNBC who have residual disease; KEYNOTE-756 evaluating KEYTRUDA plus chemotherapy in patients with high-risk, early-stage estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer; TroFuse-010 evaluating KEYTRUDA plus sacituzumab tirumotecan (sac-TMT), an investigational trophoblast cell-surface antigen 2 (TROP2)-directed antibody-drug conjugate that Merck is developing in collaboration with Kelun-Biotech, compared to sac-TMT alone and compared to physician’s choice of treatment in patients with unresectable locally advanced or metastatic ER+/HER2- breast cancer; and TroFuse-012 evaluating KEYTRUDA plus sac-TMT versus physician’s choice of treatment in patients with TNBC who received KEYTRUDA-based neoadjuvant therapy and did not achieve a pathological complete response (pCR) at surgery.

About KEYNOTE-522

KEYNOTE-522 (ClinicalTrials.gov, NCT03036488), is a randomized, double-blind Phase 3 trial. The dual primary endpoints were pCR rate, defined as pathological stage ypT0/Tis ypN0 at the time of definitive surgery, and event-free survival, defined as the time from randomization to the time of first occurrence of either disease progression that precluded definitive surgery, a local/distant recurrence, a second primary cancer or death from any cause. A key secondary endpoint was OS. The study enrolled 1,174 patients who were randomized 2:1 to receive either:

The KEYTRUDA regimen: KEYTRUDA plus chemotherapy (paclitaxel and carboplatin), followed by KEYTRUDA plus chemotherapy (cyclophosphamide and either doxorubicin or epirubicin) as neoadjuvant therapy prior to surgery, followed by KEYTRUDA monotherapy as adjuvant therapy post-surgery (n=784) or;
The chemotherapy-placebo regimen: Placebo plus chemotherapy (paclitaxel and carboplatin), followed by placebo plus chemotherapy (cyclophosphamide and either doxorubicin or epirubicin) as neoadjuvant therapy prior to surgery, followed by placebo monotherapy as adjuvant therapy post-surgery (n=390).
About triple-negative breast cancer (TNBC)

Triple-negative breast cancer is the most aggressive type of breast cancer, which has the highest risk of recurrence within the first five years after diagnosis and is associated with worse outcomes compared to other forms of breast cancer. Approximately 10-15% of patients with breast cancer are diagnosed with TNBC. While some breast cancers may test positive for estrogen receptors, progesterone receptors or overexpression of human epidermal growth factor receptor 2 (HER2), TNBC tests negative for all three. Triple-negative breast cancer tends to be more common in people who are younger than 40 years of age, who are Black or who have a BRCA1 mutation.

On May 28, 2024 Labcorp (NYSE: LH), a global leader of innovative and comprehensive laboratory services, reported that members of the executive management team will participate in a presentation at the 44th Annual William Blair Growth Stock Conference on Tuesday, June 4 at 2:00 p.m. (CT) (Press release, LabCorp, MAY 28, 2024, View Source [SID1234643737]).

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