On April 16, 2023 Chimeric Therapeutics (ASX:CHM, "Chimeric" or the "Company"), the only ASX-listed clinical
stage cell therapy company, reported that it has received ethics approval for the initiation of a multi-site Phase 1B clinical trial of CHM 1101 in patients with recurrent and/ or progressive glioblastoma multiforme (GBM) (Press release, Chimeric Therapeutics, APR 26, 2023, View Source [SID1234630478]). This new chapter in the development of CHM 1101 will see Chimeric leading a two-part Phase 1B clinical study enrolling patients with recurrent and/ or progressive GBM at multiple clinical trial sites.

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Part A of the trial will treat 3-6 patients, completing the Phase 1 CHM 1101 dose escalation/confirmation study that was initiated at City of Hope Cancer Centre. At the end of 2023, an assessment of clinical safety and efficacy data from the Phase 1 dose escalation/ confirmation cohort will be undertaken. Should the results of that assessment
support further development, Part B of the trial design would be initiated.

Part B of the trial is a dose expansion cohort designed to enroll 12-26 patients with recurrent and/ or progressive GBM using the recommended Phase 2 dosing plan and assessing for efficacy and safety.

Upon successful completion of the Part B dose expansion cohort, a registration trial will be initiated in alignment with regulatory feedback.

"Expanding our clinical program to additional sites is critical to our mission to deliver our medicines to the patients who need them," said Dr Jason Litten, Chief Medical Officer of Chimeric Therapeutics. "The two-part trial design also ensures that we are positioned to move rapidly into the dose expansion cohort upon a positive clinical assessment of the Phase 1 data at the end of 2023."

Additional details on the CHM Phase 1B trial design and objectives are being presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting as part of the Central Nervous System Tumors section on June 3, 2023.

About CHM 1101:

CHM 1101 (CLTX CAR T) is a first in class CAR T therapy that has the potential to address the high unmet medical need of patients with recurrent or progressive glioblastoma, patients who have a poor prognosis, with limited treatment options and a median survival of less than 1 year (Gallego. Curr Oncol, 2015).

CHM 1101 cells uniquely utilize chlorotoxin (CLTX), a 36-amino acid peptide derived from deathstalker scorpion venom, as the tumour-targeting component of the chimeric antigen For personal use only receptor (CAR).

In preclinical models, CHM 1101 CAR T cells have been shown to bind more broadly and specifically to GBM cells than other targeting domains like EGFR, HER-2 or IL-13. CHM 1101 cells also demonstrated potent antitumor activity against glioblastoma while not exhibiting any off-tumor recognition of normal human cells and tissues, indicating a potentially optimal safety and efficacy profile.

CHM 1101 is currently being studied in an ongoing phase 1A clinical trial in recurrent / progressive glioblastoma at City of Hope Cancer Centre in California. Outcomes from the initial two dose levels of the Phase 1A trial have been previously presented and demonstrated patient safety with a disease stability rate of approximately 70%.

On April 25, 2023 Incurix reported preclinical results of MYC (C-Myc) inhibitor ‘ICX-101’ at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (ACCR 2023) (Press release, Incurix, APR 25, 2023, View Source;idx=92&page=1&code=news [SID1234643577]).

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ICX-101 is a substance that Incurix licensed (L/I) from the National Cancer Center and the Korea Research Institute of Chemical Technology in 2023, and Incurix CEO Jeong Kyeong-chae led the drug development. Incurix is ​​developing ICX-101 in the preclinical stage.

Choi Won-young, a senior researcher at the National Cancer Center, presented the results of in vitro research on ICX-101 at the ACCR held in Orlando, USA on the 18th (local time).

ICX-101 is a MYC inhibitor, a small molecule compound that prevents MYC from binding to DNA by forming a dimer with MAX. MYC is a cancer-causing transcription factor and is known to play an important role in cell division and cell survival along with MAX.

In this study, the National Cancer Center evaluated the drug responsiveness of ICX-101 in lung cancer patient-derived cancer cells (PDC). As a result of the study, it was confirmed that cancer cells with higher MYC mRNA levels were more responsive to ICX-101. In addition, MYC expression was found to be high in lung cancer patient-derived cells, especially small cell lung cancer (SCLC).

Specifically, the National Cancer Center collected cancer tissues from 82 lung cancer patients and classified cancer cells according to histological type. Accordingly, a total of 100 samples were collected, including 82 adenocarcinoma, 10 squamous cell carcinoma, 4 non-small cell lung cancer (NSCLC), and 4 SCLC. As a result of checking the expression level of MYC in these samples, the expression level of MYC was highest in SCLC samples and was found to be significantly higher than that in NSCLC (p=0.004).

Next, the degree of response to ICX-101 was evaluated when the samples were classified into three groups according to the level of MYC expression: top 25%, middle 50%, and bottom 25%. As a result, it was found that samples in the top 25% of MYC expression levels responded more sensitively to ICX-101 than samples in the bottom 25%. It was confirmed that sensitivity to ICX-101 increases as the level of MYC expression increases.

Senior Researcher Choi said, "Looking at the overall survival data of patients from whom PDC was collected, it was confirmed that patients with high MYC expression had a poorer prognosis than patients with low MYC expression. Based on this data, from a long-term perspective, "It is expected that ICX-101 can induce a good response in patients with poor prognosis due to high MYC expression," he said.

Additionally, Senior Researcher Choi explained, "Because SCLC samples were found to have higher MYC expression than NSCLC, we view this as a promising indication for ICX-101."

On April 25, 2023 Erasca, Inc. (Nasdaq: ERAS), a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers, reported the publication of results in the Journal of Clinical Oncology from the expansion arm of a Phase 1b open label study evaluating pan-RAF inhibitor naporafenib plus MEK inhibitor trametinib (MEKINIST) in patients with NRAS-mutant (NRASm) melanoma (Press release, Erasca, APR 25, 2023, View Source [SID1234639358]).

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"These data support the promising anti-tumor potential of naporafenib in combination with trametinib in patients with NRASm melanoma. There are currently no approved targeted therapies for tumors with NRAS mutations, a mutation type associated with poor prognosis that afflicts about 20% of patients with melanoma," said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. "The post-immune checkpoint inhibitor setting is an area of high unmet medical need with the current standard of care being chemotherapy. The NEMO trial evaluating chemotherapy in patients with treatment-naïve NRASm melanoma demonstrated an objective response rate (ORR) of 7% and a median progression-free survival (mPFS) of 1.5 months. By comparison, the combination confirmed ORR of 47% and an mPFS of 5.5 months with 200 mg BID of naporafenib and 1 mg QD of trametinib observed by de Braud et al. support the initiation of our pivotal Phase 3 SEACRAFT-2 trial in NRASm melanoma. The higher response rates and prolonged PFS also further reinforce the advantage of this specific dosing regimen. We look forward to working with health authorities this year in order to support first patient dosing in SEACRAFT-2 during the first half of 2024."

Publication Highlights
Initial Evidence for the Efficacy of Naporafenib in Combination with Trametinib in NRAS-Mutant Melanoma: Results From the Expansion Arm of a Phase 1b, Open-Label Study
Dual blockade of the RAS/MAPK pathway has proven to be highly efficacious in patients with BRAF-mutant melanoma. However, similar dual blockade has not been approved in patients with NRASm melanoma. This Novartis-sponsored Phase 1b study evaluated the safety and preliminary efficacy of naporafenib plus trametinib at two recommended doses for expansion in patients with NRAS-mutant melanoma.

Naporafenib plus trametinib demonstrated promising preliminary antitumor activity in heavily pretreated patients
The safety profile of the combination was manageable with low discontinuation rates due to adverse events
Naporafenib 200 mg BID + trametinib 1 mg QD vs. naporafenib 400 mg BID + trametinib 0.5 mg QD:
Confirmed objective response rate: 46.7% (7 of 15 patients) vs. 13.3% (2 of 15 patients)
Median duration of response: 3.75 months vs. 3.75 months
Median progression-free survival: 5.5 months vs. 4.2 months
About Naporafenib

Naporafenib (formerly LXH254) is a potent and selective pan-RAF inhibitor, with a potential first-in-class and best-in-class profile. Naporafenib has been dosed in over 500 patients to date, whereby safety, tolerability, pharmacokinetics, and pharmacodynamics have been established in both monotherapy and in certain combinations, with clinical proof-of-concept (PoC) data in combination with trametinib for NRAS-mutant (NRASm) melanoma, which includes NRAS Q61X melanoma, and preliminary clinical PoC data with trametinib for RAS Q61X in non-small cell lung cancer (NSCLC). Erasca plans to focus initially on advancing and securing regulatory approval for naporafenib plus trametinib in NRASm melanoma as part of the planned Phase 3 SEACRAFT-2 trial and in RAS Q61X tissue agnostic solid tumors as part of the planned Phase 1b SEACRAFT-1 trial, respectively. Erasca is also exploring additional combinations of naporafenib with other proprietary therapeutic agents in our pipeline.

On April 25, 2023 AnHorn Medicines, a private biotechnology company focused on the development of precision medicines for degrading disease-causing proteins, reported the successful completion of a $10 million Series A financing (Press release, AnHorn Medicines, APR 25, 2023, View Source [SID1234632788]). This financing will enable AnHorn Medicines to expedite the growth of its pipeline, advance development of drug candidates, and enhance its platform capabilities to rationally design bi-functional degraders and molecular glues that target the known drivers of cancers and other diseases currently unaddressed by conventional methods.

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The Series A financing was led by Taiwania Capital with participation from new investors included TaiAn Technologies, Industrial Technology Investment Corporation, Hong Tai Electric Industrial, Black Marble Capital Management, Mega Venture Capital and Sunplus Technology.

In addition to financial resources, this round of investment brings impressive experience and intellectual resources to AnHorn Medicines in the form of two new members of the Board of Directors:

Bryan Kao, Ph.D., Sr. Investment Manager, Taiwania Capital;

Jo Shen, Ph.D., Common Director;

Chu-Chiang Lin, Ph.D., President and Chief Executive Officer of AnHorn Medicines.

"We are pleased to have the support of this strong group of investors who share our vision and believe in our approach to expand the field of protein degradation into a broader array of diseases." said Chu-Chiang Lin, Ph.D., CEO of AnHorn Medicines.

AnHorn Medicines has built a next-generation protein degradation platform with highly focused and scalable chemical libraries that target critical disease-causing proteins. The team comprise diverse specialties which consists of medicinal chemistry, structural biology, machine learning-based chemistry, and pharmacology.

On April 28, 2023 IN8bio, Inc. (Nasdaq: INAB), a clinical-stage biopharmaceutical company focused on innovative gamma-delta T cell therapies, reported FDA orphan drug designation for INB-400 and INB-410, covering a broad range of malignant glioma treatments, including newly diagnosed GBM (Press release, In8bio, APR 25, 2023, View Source [SID1234630669]). As an industry leader in gamma-delta T cell development, this milestone marks the first genetically modified gamma-delta T cell therapy to receive this designation, which offers potential incentives such as 7-year market exclusivity.

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In December 2022, the FDA cleared IN8bio’s investigational new drug application (IND) for a Phase 2 clinical trial in newly diagnosed GBM for INB-400. With Institutional Review Board (IRB) review and site initiation ongoing, patient enrollment is expected to begin in the second half of 2023.

"Our goal is to achieve our Mission of Cancer Zero by eradicating cancer cells and improving patient outcomes," said IN8bio CEO and co-founder, William Ho. "Our novel approach combines engineered, chemo-resistant gamma-delta T cells with standard-of-care treatments to amplify immune signals, maximize tumor killing, and eliminate more cancer cells. We eagerly anticipate enrolling our first Phase 2 patients for INB-400 later this year."

GBM, a highly aggressive and difficult-to-treat brain cancer, has remained largely unchanged in treatment options for over 18 years, with a median progression-free survival of 6-7 months and overall survival of 14-16 months.

Orphan drug designation benefits IN8bio through incentives such as potential additional market exclusivity following approval, tax credits on qualified US clinical trials, eligibility for orphan drug grants, and exemption from certain fees. With this milestone, IN8bio continues to progress its pipeline programs and will provide further clinical updates on its pipeline at medical meetings throughout the year.

About INB-400

INB-400 is IN8bio’s DeltEx chemotherapy resistant autologous and allogeneic DRI technology. Allogeneic INB-400 will expand the application of DRI gamma-delta T cells into other solid tumor types through the development of allogeneic or "off-the-shelf" DeltEx DRI technology.