On March 7, 2022 GlycoMantra, a University of Maryland, Baltimore (UMB) startup company developing therapeutics for unmet medical needs in prostate cancer, NASH liver fibrosis, and type 2 diabetes, reported that has been granted worldwide, exclusive rights to a UMB technology to advance the company’s pipeline of therapeutics for treating drug-resistant metastatic colorectal cancer (mCRC) (Press release, GlycoMantra, MAR 7, 2022, View Source [SID1234614714]).

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According to the American Society of Cancer Oncology, colorectal cancer (CRC) is the second leading cause of cancer death among men and women in the U.S., totaling about 53,000 deaths per year. Drug resistance to CRC is a primary challenge and mCRC remains a lethal disease. Although 5-fluorouracil (5-FU)—one of the current standards of care for patients with mCRC—exerts clinical benefit, all patients have acquired resistance to the drug over time.

To address drug resistance, GlycoMantra is developing a novel combination therapy, using two natural bioingredients that are expected to treat mCRC and 5-FU-resistant mCRC in multiple pathways: inhibition of the neoangiogenesis to reduce cancer stem cells (CSCs) and increasing apoptosis (cell death). Aditi Banerjee, PhD, of the University of Maryland School of Medicine Department of Pediatrics, is the lead inventor of the technology.

"The combination therapy we’re pursuing is anticipated to be a significant advancement in the arsenal against mCRC. By exerting multiple and prolonged attack on tumors, our goal would be to achieve longer survival of mCRC patients with use of this approach," said Hafiz Ahmed, PhD, Founder, President, and CEO of GlycoMantra. "This licensing agreement with the University of Maryland, Baltimore will allow us to advance our very important research and development."

So far, the efficacy of the combination drug has been demonstrated in a preclinical model. IND-enabling experiments such as toxicity and PK/PD are the next steps prior to beginning human clinical trials.

Phil Robilotto, DO, MBA, associate vice president of UMB’s Office of Technology Transfer and director of UM Ventures at Baltimore said, "We are thrilled to collaborate with Dr. Ahmed, an experienced scientist who has successfully implemented both short and long-term strategic R&D programs focused on cancer and metabolic disease. I’m excited to see what the future holds for his team and for patients."

On March 7, 2022 Immix Biopharma, Inc. (Nasdaq: IMMX) ("ImmixBio", "Company", "we" or "us"), a biopharmaceutical company pioneering Tissue-Specific Therapeutics (TSTx) targeting oncology and immuno-dysregulated diseases, reported the IMMX Milestone Day Event, to be held on April 5, 2022 (Press release, Immix Biopharma, MAR 7, 2022, View Source [SID1234609550]). At the Event, management plans to discuss current financial position, milestones, and new opportunities presented by current market volatility.

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"With conflict in Europe and attendant volatility in capital markets, we believe it is appropriate to discuss that ImmixBio not only continues to be on track to achieve clinical data milestones as planned with the funding we raised in our IPO, but also act on new opportunities presented," said Ilya Rachman, MD PhD, Chief Executive Officer of ImmixBio. "Each day we are advancing ImmixBio forward towards the milestones we have committed to our investors, stakeholders, and patients."

"We raised $24.2 million in total gross proceeds 3 months ago at the end of December including full exercise of the underwriters’ over-allotment option in connection with our IPO," said Gabriel Morris, Chief Financial Officer of ImmixBio. "With Dr. Rachman’s experience as a clinical investigator for approved therapies, we believe we are ideally positioned to take advantage of market uncertainty to accomplish milestones with increasing capital efficiency."

On March 7, 2022 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, reported that a manuscript has been published in the peer-reviewed journal Gastroenterology, authored by Curis collaborators at Washington University School of Medicine in St. Louis, on the role of IRAK4 in pancreatic ductal adenocarcinoma (PDAC) and the preclinical efficacy of emavusertib (CA-4948), a novel, small molecule IRAK4 inhibitor, in combination with checkpoint immunotherapy (Press release, Curis, MAR 7, 2022, View Source [SID1234609586]).

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"Through our emavusertib clinical trials, we have seen the potential of targeting IRAK4 in indications like non-Hodgkin’s lymphoma, acute myeloid leukemia and myelodysplastic syndromes," said James Dentzer, President and Chief Executive Officer of Curis. "Given the early, but compelling preclinical data outlined in Gastroenterology, IRAK4 targeting may have a broader application in treating solid tumors such as pancreatic cancer. We are thrilled to continue to identify new opportunities to potentially expand the development of emavusertib into additional cancer types as we work towards our goal of delivering novel, innovative cancer therapeutics in areas with significant unmet patient need."

The manuscript titled "IRAK4 signaling drives resistance to checkpoint immunotherapy in pancreatic ductal adenocarcinoma" concluded that tumor IRAK4 drives T-cell exhaustion in PDAC and is a promising therapeutic target when combined with checkpoint immunotherapy. Specifically, the experiments demonstrated that IRAK4 controls the NF-kB pathway and production of multiple checkpoint ligands, suppressive chemokines/cytokines, as well as hyaluronan synthase 2, all of which suppress T cell immune function against cancer. The study demonstrated that in a genetic mouse model that develops highly aggressive pancreatic cancer, IRAK4 can be targeted to overcome the immunosuppressive tumor microenvironment and drive response to checkpoint immunotherapy and validate the study of CA-4948 as a means to improve immunotherapeutic response in pancreatic cancer. The study team further confirmed this finding by generating a genetic mouse model in which the IRAK4 gene is deleted from the pancreatic cancer, providing firm evidence that IRAK4 is a promising therapeutic target in this deadly disease.

"Historically, the tumor microenvironment’s strong defense mechanisms have made cancers such as PDAC nearly impossible to treat effectively. Checkpoint immunotherapies, which have had a groundbreaking impact on other areas of oncology, are largely ineffective in PDAC," said Dr. Kian-Huat Lim, MD, PhD, Associate Professor of Medicine at Washington University School of Medicine, and Director of the GI Oncology Program. "Given the role of IRAK4 in NF-kB activation, we sought to explore whether there could be a translational benefit to targeting IRAK4 in PDAC. The results of our preclinical study show the promising effects of targeting IRAK4 in combination with chemotherapy and checkpoint immunotherapy, highlighting the potential of emavusertib to deliver effective therapeutic options to pancreatic cancer patients, who continue to have very limited therapeutic options."

The manuscript is available online at View Source(22)00201-3/pdf.

About Emavusertib (CA-4948)

Emavusertib is an IRAK4 kinase inhibitor and IRAK4 plays an essential role in the toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling pathways, which are frequently dysregulated in patients with AML and MDS. Third parties have recently discovered that the long form of IRAK4 (IRAK4-L) is oncogenic and preferentially expressed in over half of patients with AML and MDS. The overexpression of IRAK4-L is believed to be driven by a variety of factors, including specific spliceosome mutations such as SF3B1 and U2AF1.

On March 7, 2022 Harpoon Therapeutics, Inc. (NASDAQ: HARP), a clinical-stage immunotherapy company developing novel T cell engagers, reported that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation for HPN328, a delta like ligand 3- (DLL3) targeting TriTAC, for the treatment of small cell lung cancer (SCLC) (Press release, Harpoon Therapeutics, MAR 7, 2022, View Source [SID1234609604]). A Phase 1/2 clinical trial is currently ongoing for HPN328 in the SCLC patient population.

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"Orphan Drug Designation for HPN328 is a significant milestone that underscores the need for additional treatments for patients suffering from small cell lung cancer and HPN328’s potential to contribute to this unmet medical need," stated Julie Eastland, President and CEO, Harpoon Therapeutics. "We are pleased with the clinical progress of HPN328 and remain focused on dose escalation with the goal to determine the recommended Phase 2 dose by the end of this year."

The FDA’s Orphan Drug Designation program provides orphan status to drugs defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases that affect fewer than 200,000 people in the United States. Orphan Drug Designation qualifies the sponsor of the drug for certain development incentives, including tax credits for qualified clinical testing, prescription drug user fee exemptions and potential eligibility for seven-year marketing exclusivity upon FDA approval.

About the Phase 1/2 Trial for HPN328

HPN328 is a TriTAC that binds to human and non-human primate DLL3, CD3ε, and albumin with similar affinities. The Phase 1/2 trial is an open-label study of HPN328 as monotherapy to assess the safety, tolerability and pharmacokinetics in patients with advanced cancers associated with expression of DLL3. The first part of the trial is designed to determine a dose for additional clinical investigations.

As of the December 13, 2021 clinical update provided by Harpoon, 15 patients had been enrolled in dose cohorts ranging from 15 µg to 7200 µg per week using both fixed and step dose administration once weekly by intravenous infusion. Enrolled patients had a median of 2 lines (range 1 to 5) of prior therapy and included small cell lung cancer patients who had relapsed after platinum chemotherapy and patients with other malignancies with high grade neuroendocrine tumors associated with DLL3 expression. HPN328 has been well tolerated with Grade 1-2 cytokine release syndrome (CRS) reported in 33% of patients, no DLTs observed and MTD had not been reached. Among four patients with small cell lung cancer receiving the two highest doses tested to date, 1215 µg fixed dose and 3600-7200 µg step dose, three had target lesion reduction, including 1 confirmed RECIST partial response. The patient with a cPR experienced a target lesion reduction of 53% at week 10.

Following dose escalation, Harpoon may further evaluate the safety and efficacy of HPN328 in additional parallel cohorts. The primary outcome measure will be to determine efficacy for the Phase 2 dose based on the overall response rate as determined by RECIST. For additional information about the trial, please visit clinicaltrials.gov using the identifier NCT04471727.

On March 7, 2022 Arctoris, a tech-enabled biopharma company, and Evariste Technologies, an AI-drug discovery company, reported they have formed a joint venture to identify novel small molecule kinase inhibitors for treatment of patients with Non-Small Cell Lung Cancer (NSCLC) (Press release, Arctoris, MAR 7, 2022, View Source;utm_medium=rss&utm_campaign=arctoris-and-evariste-technologies-form-a-joint-venture-to-identify-novel-small-molecule-cmet-inhibitors-for-non-small-cell-lung-cancer [SID1234612705]).

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Current treatment options for NSCLC are limited, especially in advanced stages. It has been shown that the proto-oncogene cMet is mutated or upregulated in approximately 5% of all NSCLC cases. While cMET has been successfully targeted by two recently approved drugs (Tepotinib, Capmatinib), rapid development of resistance has been reported and there is a clear need for improved second-generation cMET inhibitors to overcome resistance.

The two companies are combining their platforms for AI-guided and robotics-powered drug discovery to develop a set of novel kinase inhibitors against cMET. The partnership will bring together two highly synergistic approaches – quantitative decision making and state-of-the-art generative chemistry, combined with real-time biological and biochemical profiling and data generation, to significantly accelerate the design-make-test-analyze cycle. The two companies will also use their strong links to leading centres for NSCLC treatment to leverage clinical insights, inform their discovery and development efforts and directly address clinically relevant liabilities limiting the effectiveness of currently available therapies.

"We are really excited to be working with Arctoris on this project. There is a huge need for next generation cMET inhibitors for NSCLC. This is a cancer that affects millions globally, and we hope that we can bring meaningful benefit to some of these lives in the near future," shares Dr. Nicholas Firth, CEO of Evariste Technologies.

Arctoris CEO Martin-Immanuel Bittner MD DPhil FRSA commented on the joint venture, "Together with our partners at Evariste, we are developing novel treatment options in NSCLC against a fully validated target, where first generation inhibitors can be improved on in a clinically meaningful way. Combining patient-derived insights on resistance and toxicity patterns with AI-powered molecule design and our robotic platform, Ulysses, we aim to develop superior next generation inhibitors within a significantly accelerated time frame."

The collaboration between Arctoris and Evariste is already underway and has identified novel, active chemical matter. "We look forward to keeping our community updated about the progress we are making within the joint venture between Evariste Technologies and Arctoris. We have had an incredible start already, and we look forward to continuing our work to develop better treatments options for patients worldwide", shares Bittner.