On August 3, 2021 NaviFUS’ focused ultrasound (FUS) therapy system (NaviFUS) reported that it was recently approved for use in a new clinical trial by the Taiwan Food and Drug Administration (TFDA). It will be initiated shortly at Linkou Chang Gung Memorial Hospital (Press release, NaviFUS, AUG 3, 2021, View Source [SID1234585656]). The trial will investigate the "synergy" that FUS-mediated opening of the blood-brain barrier (BBB) has on improving the therapeutic effect of radiotherapy treatment in patients with end-stage primary brain tumors. Despite suffering from repeating surgeries, radiotherapy, and chemotherapy, most of these patients will eventually face tumor recurrence. Currently, while there may not be any effective treatments guaranteed to prolong survival, NaviFUS hopes that this upcoming clinical trial can result in a new, low-risk, and "Patient Friendly" option for patients who have already exhausted first and second-line treatments or failed radiotherapy treatment previously. If this combined treatment can safely enhance the effect of radiotherapy, NaviFUS’ believes this treatment can also be extended to metastatic brain tumors from lung cancer, breast cancer, etc. The market potential for this treatment is expected to be more than $2 billion US dollars.

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The principle behind the "synergy" of this combined treatment is based on findings that the blood flow and oxygen concentration in the tumor area are often insufficient due to rapid proliferation of tumor cells. As a result of these hypoxic conditions, free radicals are not easily generated during radiation treatment, resulting in low radiotherapy efficacy; the opening of the blood-brain barrier is expected to change the tumor microenvironment by improving the blood flow and oxygen content of tumor tissues, which promotes the formation of free radicals and produces a radio-sensitization effect, so that the same dose of radiotherapy may bring better results without adding negative side effects.

NaviFUS has successively published research on how the opening of the BBB can enhance the therapeutic effect of radiotherapy last year at Focused Ultrasound Foundation’s International Symposium on Focused Ultrasound and this year at International Symposium for Therapeutic Ultrasound (ISTU 2021). In preclinical studies, preliminary results confirmed that the oxygen content of brain tissue is significantly increased after opening the BBB, resulting in an enhanced radiotherapy and tumor-inhibiting effect. Under these conditions, low radiotherapy doses may yield high-dose therapeutic effects and significantly reduced serious side effects attributed to high-dose radiotherapy.

At the same time, NaviFUS is conducting a FUS-mediated BBB opening combined with bevacizumab (Avastin) clinical trial at Linkou Chang Gung Memorial Hospital. After repeatedly opening the BBB and long-term treatment with Avastin, preliminary results have shown positive signs of superior tumor progression control at the tumor treatment sites in patients; NaviFUS plans to run a similar trial simultaneously at Stanford University, which they expect to be approved by the US FDA’s IDE review before the end of the year.

Dr. Arthur Lung, Chief Executive Officer of NaviFUS, expresses great optimism about the therapeutic potential of the NaviFUS System. "If these two non-invasive FUS treatments for brain tumors can be successfully developed, they can offer non-invasive treatment options with improved efficacy and minimal side effects." As the NaviFUS System continues its development of next-generation treatments on its platform, it has garnered much interest worldwide and has partnered with organizations conducting clinical or academic research in FUS through its Research-Only FUS device. For further inquiries on this model, please contact NaviFUS directly.

On August 3, 2021 Nanoform, an innovative nanoparticle medicine enabling company, reported that Proof of Concept studies may now be performed for Boehringer Ingelheim to assess the added value Nanoform’s award-winning CESS technology can deliver to its drug development projects (Press release, Boehringer Ingelheim, AUG 3, 2021, View Source [SID1234585655]).

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The two parties have executed a master services agreement (MSA) to initiate projects in the pre-clinical early development space with the aim of solving the ever-growing challenge of poor bioavailability and solubility in new drug candidates – a leading cause of drug development failure.

Christian Jones, CCO of Nanoform, commented: "Wider uptake of the latest technological innovations is essential to address the low success rates for new drug candidates in Pharma. We are delighted to collaborate with Boehringer Ingelheim to evaluate how our proprietary CESS platform can help more novel therapies reach the patients who need them. This is the first step toward what we hope will be a long and fruitful partnership between our companies."

On August 3, 2021 Ryvu Therapeutics (WSE: RVU), a clinical stage drug discovery and development company focusing on novel small molecule therapies that address emerging targets in oncology, reported that it is scheduled to participate in the following investor conferences (Press release, Ryvu Therapeutics, AUG 3, 2021, View Source [SID1234585654]):

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12th Annual Wedbush PacGrow Healthcare Conference on Tuesday, August 10 – Wednesday, August 11, 2021. Ryvu will participate in a panel entitled "Synthetic Lethal (Weapon)" on August 10 at 11:30am-12pm EDT and host investor meetings during the conference.

Morgan Stanley 19th Annual Global Healthcare Conference on Thursday, September 9, 2021 – Wednesday, September 15, 2021. Ryvu will host investor meetings during the conference.

H.C. Wainwright 23rd Annual Global Investment Conference, on Monday, September 13 – Wednesday, September 15, 2021. Ryvu’s corporate presentation will be available on-demand starting on September 13 at 7:00 AM (ET), and Ryvu will host investor meetings during the conference

On August 3, 2021 GT Biopharma, Inc. (NASDAQ: GTBP), a clinical stage biopharmaceutical company focused on developing target-directed, tri-specific Natural Killer (NK) cell engager therapies (TriKE) incorporating interleukin 15 (IL-15) for the treatment of cancer, reported that preclinical results for GTB-5550, its B7H3 TriKE product candidate as a prospective therapy for the treatment of several different types of cancers (Press release, GT Biopharma, AUG 3, 2021, View Source [SID1234585653]).

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GTB-5550 TriKE was evaluated in several preclinical models overexpressing B7H3, and was found to be effective at promoting NK cell killing of multiple cancer cell types. B7H3 is over-expressed on several cancer types including non-small cell lung cancer, squamous cell carcinoma, and breast, renal, pancreatic, ovarian, liver and colorectal cancers. GTB-5550 TriKE is presently undergoing GMP manufacturing scale-up in preparation for filing an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) for evaluation in humans.

B7H3 is a member of the B7 family of immune checkpoint inhibitors which includes PD-1/PD-L1 and CTLA-4/CD80. Merck’s Keytruda (pembrolizumab) and Bristol-Myer Squibb’s YERVOY (ipilimumab) targeting the PD-1/PD-L1 and CTLA-4/CD-80 checkpoints, respectively, have demonstrated significant survival benefit and are blockbuster immune-oncology therapeutics.

B7H3 expression on cancer cells is highly associated with undesirable treatment outcomes and survival time. Targeting B7H3 on cancer cells with TriKE and redirecting NK cells to attack and kill cancer cells expressing B7H3, could result in a therapeutic treatment that limits the metastatic potential and invasiveness of certain solid tumor cancers.

Anthony J. Cataldo, GT Biopharma’s Chairman and Chief Executive Officer, commented: "We are pleased to report our GTB-5550 TriKE has passed this important development milestone, and demonstrated effectiveness in promoting redirected and target-specific killing by NK cells."

On August 3, 2021 Lutris Pharma, a clinical stage biopharmaceutical company focused on improving anti-cancer therapies by reducing dose limiting side effects, reported that the first U.S. patients have been dosed as part of the Company’s phase 2 trial of lead compound, LUT014, a topically applied, novel B-Raf inhibitor, for metastatic colorectal cancer patients (mCRC) being treated with epidermal growth factor receptor (EGFR) inhibitor therapy who have developed dose-limiting acneiform lesions (Press release, Lutris Pharma, AUG 3, 2021, View Source;-a-topical-gel-for-the-reduction-of-dose-limiting-acneiform-lesions—-in-metastatic-colorectal-cancer-patients-treated-with-egfr-inhibitor-therapy-301346759.html [SID1234585652]). Recruitment and treatment of patients in Israel continues to progress. Based on the trial design, full, unblinded 28-day rolling results will be reported, as appropriate.

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The phase 2, randomized, double-blind, placebo-controlled trial is expected to enroll a total of 117 subjects at 20 sites, consisting of 15 in the U.S. (including Memorial Sloan Kettering Cancer Center in New York) and five in Israel. The trial will evaluate the efficacy and safety of two strengths of LUT014 Gel, 0.03% or 0.10%, applied once daily for 4 weeks, compared to placebo (with a randomization of 1:1:1), in patients with mCRC who develop Grade 2 EGFR inhibitor-induced acneiform lesions, with a 4-week follow up period. During an optional open label extension period, for the placebo group, subjects will receive the 0.03% concentration of LUT014.

The study’s primary endpoint is the proportion of subjects in each treatment group who reach treatment success, defined as an improvement (decrease) of at least one grade in the severity of the acneiform lesions from baseline to Day 28, based on common terminology criteria for adverse events (CTCAE) V5.0 skin and subcutaneous tissue disorders grading scale or, an improvement (increase) of at least 5 points in the total score for the skin-specific (first 13 questions) of the functional assessment of cancer therapy epidermal growth factor receptor inhibitor 18 (FACT-EGFRI-18) health related quality of life (HRQoL) questionnaire, from baseline to Day 28. Key secondary endpoints include change in the severity of acneiform lesions based on CTCAE grading scale from baseline to Days 7, 14, 21, 28, and 55; and change in the FACT-EGFRI-18 questionnaire total score for the skin-specific questions from baseline to Days 7, 14, 21, 28, and 55.

"Dosing of the first U.S. patients is a significant milestone in the progression of this international, phase 2 trial of LUT014," stated Noa Shelach, Ph.D., Chief Executive Officer of Lutris Pharma. "While EGFR inhibitors are critical treatment options, over 80% of mCRC patients experience adverse dermatological side effects, including papulopustular skin rash – also known as acneiform lesions – which reduces their quality of life, and more importantly, may lead to a reduction or discontinuation of treatment. By reversing the inhibitory effect of EGFR inhibitors on downstream proteins in the skin cells, we believe that LUT014 has the potential to become an important addition to therapeutic regimens and can have a tremendous impact for patients who currently have no other treatment options."

Mario E. Lacouture, M.D., Director of the Oncodermatology Program at Memorial Sloan Kettering Cancer Center, noted, "Development of the acneiform rash caused by EGFR inhibitors including cetuximab, panitumumab and others, may affect quality of life and consistent dosing, and in the absence of any approved treatments, there is an unmet need for approved topical therapies. Lutris’ phase 1 results in patients with mCRC were promising, with no dose limiting toxicities and a therapeutic benefit in all patients. As a result, we look forward to participating in the phase 2 trial and to the interim results later this year."

For more information on this clinical trial, please visit: www.clinicaltrials.gov, NCT04759664.

Dr. Lacouture has provided consulting and advisory services for Lutris Pharma.

About EGFR inhibitor-induced rash
EGFR is a receptor on the surface of cells which is expressed in many normal epithelial tissues, including skin. The EGFR signaling pathway is one of the most important pathways that regulate growth, survival, proliferation, and differentiation of cells. B-Raf is protein encoded by the BRAF gene and is a downstream effector component of EGFR signaling pathway. EGFR is shown to be over-activated in various human cancers, including colorectal, lung, head and neck, urinary bladder, pancreatic and breast cancers, eliciting downstream phosphorylation and activation of the MAP Kinase pathway.

Drugs called EGFR inhibitors can block the EGFR signal responsible for cell growth. Among the various types of pharmacological therapies for cancer, EGFR inhibitors are increasingly being used both as primary therapy as well as in patients who have failed prior chemotherapy. Although effective as anti-cancer therapy leading to tumor shrinkage, EGFR inhibitors have a number of adverse reactions associated with their use. The majority of patients treated with EGFR inhibitors will experience adverse dermatological side effects typically manifested as a papulopustular skin rash, also known as acneiform lesions, which can impact quality of life and affect adherence to therapy.

About LUT014
LUT014 is a novel B-Raf inhibitor which is applied topically on the skin. The B-Raf protein is part of the EGFR pathway, and has shown to be mutated in some human cancers such as melanoma cancer. Blocking the B-Raf pathway in B-Raf mutated cancer cells leads to tumor shrinkage, but when the same pathway is blocked in normal, non-mutated cells, the opposite happens: the MAP Kinase pathway is activated and cells start growing. This phenomenon is recognized as the paradoxical effect of B-Raf Inhibitors. LUT014 harnesses this paradoxical effect in order to reverse the effect of EGFR inhibitors on downstream proteins in the skin cells, thereby reducing dose-limiting acneiform lesions associated with EGFR inhibitor treatment.