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Pacylex Announces Orphan Drug Designation Granted to PCLX-001 for the Treatment of Acute Myeloid Leukemia

On October 14, 2022 Pacylex reported that the U.S. Food and Drug Administration (FDA) granted PCLX-001 Orphan Drug Designation for "treatment of patients with acute myeloid leukemia (Press release, Pacylex Pharmaceuticals, OCT 14, 2022, View Source [SID1234645060])." PCLX-001 is a first-in-class N-myristoylation inhibitor in clinical development by Pacylex. PCLX-001 is currently being studied in non-Hodgkin lymphoma (NHL) and solid tumor cancer patients at 4 sites in Canada. Pacylex has filed an IND to study PCLX-001 in the U.S. in AML patients.

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Dr. Michael Weickert, Pacylex’s President and CEO commented, "The 5-year survival rate for AML patients 20 and older is only 27%. Patients relapse despite existing therapies. We are developing a first-in-class therapy that tackles AML in a new way that has been very effective in disease models and may be synergistic with other approaches. Our trial will offer relapsed patients another option. This Orphan Drug Designation for PCLX-001 recognizes the importance of this potential new therapy for these patients."

The planned US study will be the first time an NMT inhibitor is tested in AML patients. The U.S. Department of Defense recently awarded a grant of $1.4 million to treat AML patients with PCLX-001. "Our ongoing clinical trial in people with NHL and solid tumors showed PCLX-001 was well-tolerated and achieved drug exposures likely to benefit AML patients," said Dr. John Mackey, CMO of Pacylex. "We look forward to treating AML patients with PCLX-001 in the near future."

In animal models of AML, PCLX-001 monotherapy produced complete remissions in subcutaneous AML cell line derived xenografts (CDXs). In tail-vein injected AML patient derived xenografts (PDXs), PCLX-001 treatment resulted in up to 95% reduction of human peripheral blood and bone marrow CD45+ cells, which include the malignant stem cell population responsible for disease relapse.

The ongoing clinical PCLX-001 trial in NHL and solid tumor patients is registered at ClinicalTrials.gov Identifier: NCT04836195.

The U.S. FDA Orphan Drug Designation is only granted to investigational therapies addressing medical diseases or conditions that affect fewer than 200,000 people in the United States. Orphan drug designation provides several benefits to drug developers, including assistance in the drug development process, tax credits for clinical costs, exemptions from certain FDA fees and seven years of post-approval marketing exclusivity.

PCLX-001
PCLX-001 (aka DDD86481) is a first-in-class, small molecule NMT inhibitor originally developed by the University of Dundee Drug Discovery Unit as part of a program to treat African sleeping sickness, funded by Welcome Trust. Pacylex is developing PCLX-001 in the form of a once-a-day pill initially to treat leukemia and lymphoma. PCLX-001 has also been shown to inhibit the growth of lung and breast cancer tumors in animal models. In leukemia, lymphoma and breast cancer patients, the levels of NMT2 is correlated with survival, suggesting an important biological role in these cancers. In tests using cultured cancer cells in vitro, PCLX-001 is at least ten times as potent as ibrutinib (Imbruvica) and dasatinib (Sprycel), two clinically approved drugs currently used to treat hematologic malignancies.

Genor Biopharma officially launched the Phase I/II Clinical Trial of GB263T in China

On October 14, 2022 Genor Biopharma (Stock code: 6998.HK) reported that the first patient has been successfully dosed in a Phase I/II clinical trial of GB263T, a novel EGFR/cMET/cMET trispecific therapeutic antibody, in China for the treatment of patients with advanced Non-Small Cell Lung Cancer (NSCLC) and other solid tumors (Press release, Genor Biopharma, OCT 14, 2022, View Source [SID1234629909]).

Previously, the first patient has been successfully dosed in this GB263T FIH study in Australia.

About GB263T（EGFR/cMET/cMET）

GB263T is the world’s first EGFR/cMET/cMET tri-specific antibody targeting EGFR and two different epitopes of cMET and has been designed with the goal of improving safety and efficacy. Thus, GB263T is a highly differentiated tri-specific antibody that exhibits multiple mechanisms of action to inhibit primary and secondary EGFR mutations and cMET signaling pathway simultaneously. The unique sequential binding feature whereby c-MET VHH2 binding depends on c-MET VHH1 binding expands the safety and efficacy window.

Preclinical studies showed that GB263T potently blocked ligand-induced phosphorylation of EGFR and cMET, and demonstrated better dual inhibition of EGFR and cMET signaling pathways compared to the JNJ-372 analogue. GB263T effectively induced enhanced internalization of EGFR and cMET, and downregulated the expression levels of both EGFR and cMET proteins. The in vivo anti-cancer efficacy of GB263T was demonstrated in several different tumor models, such as those with EGFR exon 20 insertion, EGFR exon 19 deletion, including C797S mutation, and various cMET alteration models. In all the models studied, GB263T demonstrated significant and dose-dependent tumor inhibition. In addition, GB263T did not show any major toxicities in monkeys, even at a high dose given for four weeks in a GLP tox study.

Pacylex Announces Orphan Drug Designation Granted to PCLX-001 for the Treatment of Acute Myeloid Leukemia

On October 14, 2022 Pacylex reported that the U.S. Food and Drug Administration (FDA) granted PCLX-001 Orphan Drug Designation for "treatment of patients with acute myeloid leukemia (Press release, Greenfire, OCT 14, 2022, View Source [SID1234624500])." PCLX-001 is a first-in-class N-myristoylation inhibitor in clinical development by Pacylex. PCLX-001 is currently being studied in non-Hodgkin lymphoma (NHL) and solid tumor cancer patients at 4 sites in Canada. Pacylex has filed an IND to study PCLX-001 in the U.S. in AML patients.

The ongoing clinical PCLX-001 trial in NHL and solid tumor patients is registered at ClinicalTrials.gov Identifier: NCT04836195.

BMF-219 Enters the Clinic for KRAS Solid Tumors

On October 14, 2022 Biomea Fusion, Inc. ("Biomea") (Nasdaq: BMEA), a biopharmaceutical company focused on the discovery and development of covalent small molecules to treat patients with genetically defined cancers and metabolic diseases, reported that the U.S. Food and Drug Administration (FDA) has cleared Biomea’s IND application to begin a Phase I/Ib trial of BMF-219, a selective, covalent menin inhibitor in patients with unresectable, locally advanced, or metastatic NSCLC, CRC, and PDAC with an activating KRAS mutation (Press release, Biomea Fusion, OCT 14, 2022, View Source [SID1234622111]).

"We are very excited to open this particular IND as we now look to validate the preclinical potential of BMF-219 in patients across several solid tumor types who have a KRAS mutation, which currently is associated with a very poor survival prognosis," said Thomas Butler, Biomea’s CEO and Chairman of the Board. "In January 2022, we mapped out perhaps one of the more aggressive clinical development plans among peer companies to initiate clinical studies of BMF-219 in up to seven tumor types by the end of 2022. I am so incredibly proud of our team’s extraordinary efforts to deliver on this plan, motivated by the persistent and significant unmet needs of numerous cancer patients."

Mr. Butler continued, "I would like to thank the FDA for their extraordinary effort clearing our IND on-time, and also our contract research organizations, our consultants, our investors, and of course TEAM FUSION for their commitment, guidance, and support in generating another broad and promising IND package for BMF-219."

KRAS is the most frequently mutated isoform amongst RAS oncogenes in human solid tumors, with high prevalence in NSCLC, CRC, and pancreatic cancer. With only one approved therapy targeting KRAS G12C for locally advanced or metastatic NSCLC, KRAS-driven tumors continue to represent a significant unmet medical need. A targeted pan-KRAS inhibitor has the potential to treat 25-35% of NSCLC, 35-45% of CRC, and approximately 90% of PDAC patients.

Menin is a scaffold protein and a required co-factor of oncogenic transcriptional proteins with functional interactions that are critical for the development of various cancers. As previously reported by Biomea Fusion, KRAS-mutant NSCLC, CRC, and PDAC cell lines and ex vivo preclinical models were highly sensitive to BMF-219. In preclinical models, high potency of BMF-219 was observed amongst various KRAS-mutant solid tumor cell lines, but not KRAS wild type, suggesting that BMF-219 broadly inhibited mutant KRAS in these tumor models. As a covalent menin inhibitor, BMF-219 has manifested advantages over the commercially KRAS-targeted inhibitor LUMIKRAS in multiple pre-clinical studies due to the independence of KRAS’ phosphorylation state within G12C tumors, and more broadly the ability to target multiple activating KRAS mutations.

About COVALENT–102

COVALENT-102 is an open-label, multi-cohort, multicenter, Phase I/Ib dose finding study evaluating the safety, tolerability, and clinical activity of escalating doses of oral BMF-219 administered to patients with unresectable, locally advanced, or metastatic NSCLC, CRC, and PDAC with a KRAS mutation.

About Non-Small Cell Lung Cancer (NSCLC)

NSCLC is the most common form of lung cancer, representing approximately 82% of all lung cancer cases or approximately 200,000 cases in the U.S. each year (Source: NCI SEER Data). Additionally, the five-year survival rate of NSCLC is approximately 25%. While lung cancer is the third most common form of cancer in the U.S. based on incidence, it contributes to the highest number of annual cancer deaths in the U.S. KRAS is the most frequently mutated oncogene in NSCLC, occurring in approximately 30% of patients. There remains a great unmet need for targeted therapies to address all KRAS driver mutations and avoid known mechanisms of resistance.

About Colorectal Cancer (CRC)

CRC is the fourth most common form of cancer and the second leading cause of cancer death in the U.S., representing approximately 150,000 cases in the U.S. each year (Source: NCI SEER Data). These cancers start in the rectum or the colon and can be diagnosed/identified early, even potentially as noncancerous polyps. The five-year survival rate of CRC is approximately 65%. Among other mutations, KRAS mutations occur in approximately 40% of patients with CRC. These mutations can not only help predict the absence of response to anti-EGFR therapy, but also result in poorer overall survival. Therefore, there’s a growing unmet need for personalized therapies for patients with KRAS-mutant colorectal cancer.

About Pancreatic Cancer (PDAC)

Pancreatic cancer is a relatively rare form of cancer in the U.S., representing approximately 60,000 cases in the U.S. each year (Source: NCI SEER Data). Pancreatic cancer is an aggressive cancer with a very low five-year survival rate of approximately 11%, indicating that there is a large unmet need. 80% of patients are diagnosed at an advanced stage, contributing to the low survival rate. KRAS mutations are found in nearly all pancreatic cancer patients and are considered as a driver of the malignant process in most of those patients.

Dynavax to Present at the H.C. Wainwright 3rd Annual Hepatitis B Virus Virtual Conference

On October 14, 2022 Dynavax Technologies Corporation (Nasdaq: DVAX), a commercial-stage biopharmaceutical company developing and commercializing innovative vaccines, reported that Ryan Spencer, Chief Executive Officer, will present at the H.C. Wainwright 3rd Annual Hepatitis B Virus Virtual Conference, on Tuesday, October 18, 2022 at 10:00 a.m. P.T (Press release, Dynavax Technologies, OCT 14, 2022, View Source [SID1234622040]).

The presentation will be webcast and may be accessed through the "Events & Presentations" page on the "Investors" section of the Company’s website at View Source