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.

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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.

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]).

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"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.

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]).

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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

On October 14, 2022 ViewRay, Inc. (NASDAQ: VRAY) reported that details relating to the release of third quarter 2022 financial results (Press release, ViewRay, OCT 14, 2022, View Source [SID1234622037]).

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ViewRay will hold a conference call to discuss results on Tuesday, November 1, 2022, at 5:00 p.m. ET. If you wish to participate live via teleconference please click here to obtain your dial-in and individual passcode.

A live webcast of the conference call will be available on the investor relations page of ViewRay’s corporate website at View Source

After the live webcast, a replay will remain available online on the investor relations page of ViewRay’s website, under "Events and Webinars".

On October 14, 2022 Phanes Therapeutics, Inc. (Phanes), a clinical stage biotech company focused on oncology, reported that it has received clearance from the US Food and Drug Administration (FDA) to commence Phase I studies with PT217, its anti-Delta-like ligand 3 (DLL3)/anti-Cluster of differentiation 47 (CD47) bispecific antibody being developed for patients with small cell lung cancer (SCLC) and other neuroendocrine cancers (Press release, Phanes Therapeutics, OCT 14, 2022, View Source [SID1234622036]). PT217 has recently been granted an orphan drug designation by the FDA for the treatment of SCLC.

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"This is the third program in our pipeline that has received IND clearance by FDA this year, which is an important milestone for Phanes and a record for a biotech company of our size. The opportunity to bring this potential first-in-class bispecific antibody to cancer patients who have such a high unmet medical need is at the core of what drives us as a company," said Dr. Ming Wang, Founder and CEO. "With a strong pipeline targeting both the adaptive and innate immunity and the bispecific antibody technology platforms we have built, Phanes is well positioned to make important impacts in delivering innovative cancer therapies."

The Phase I study will evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of PT217 in subjects with advanced or refractory cancers. Patients with the following tumor types will be eligible for screening: unresectable SCLC, large cell neuroendocrine cancer (LCNEC), neuroendocrine prostate cancer (NEPC) and gastroenteropancreatic neuroendocrine tumors (GEP-NET). Subjects must have progressed after standard therapy (at least one line of platinum-based chemotherapy with or without immune checkpoint inhibitor for SCLC) or standard therapy has proven to be ineffective, intolerable or was considered inappropriate.

SCLC is an aggressive pulmonary carcinoma hallmarked by high early mortality rates and significant morbidities throughout the disease’s progression. The 1-year survival of patients with SCLC is only 32.9%, with survival steadily decreasing with only 10.7% of patients surviving 3 years.

Phanes current clinical programs include: PT199, a differentiated anti-CD73 monoclonal antibody, enrolling at 3 US study sites and PT886, an anti-Claudin 18.2/anti-CD47 bispecific antibody, which is in study startup at The University of Texas MD Anderson Cancer Center, Houston, TX.