On December 13, 2023 Inhibitor Therapeutics, Inc. ("Inhibitor") (OTCQB: INTI) has entered into an exclusive, worldwide licensing agreement (the "License") with Johns Hopkins University (JHU) for their U.S Patent 8,980,930 (Canada Patent 2,572,223) "New Angiogenesis Inhibitors" (Press release, Inhibitor Therapeutics, DEC 13, 2023, View Source [SID1234638537]). Angiogenesis Inhibitors, as described by the National Cancer Institute, are unique cancer fighting agents as they block the growth of blood vessels that support tumor growth rather than blocking the growth of the tumor cells themselves. Inventors affiliated with JHU developed this patent, listing Itraconazole as an Active Pharmaceutical Ingredient (API) that has anti-angiogenic properties.

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The License notes field of use is for use in Prostate Cancer, Basal Cell Carcinoma including Basal Cell Carcinoma Nevus Syndrome (an orphan oncology disease), and Lung Cancer, all of which emphasize a significant unmet need. Inhibitor believes the License is a mutually beneficial agreement, yielding a modest annual royalty rate with milestone payments typical to such a license.

Within the literature Head et al1 explains the long-term recognition that angiogenesis is a requirement for tumor growth and metastasis and that growing tumors can promote angiogenesis by secreting proangiogenic factors such as VEGF, basic FGF, EGF and others. These proangiogenic factors stimulate the proliferation, migration, and differentiation of the endothelial cells that make up the inner layer of all blood vessels, causing them to form new vessels that grow towards the source of these factors, this process termed "tumor angiogenesis". It is identified that the major target of itraconazole in endothelial cells is VDAC1. VDAC1 knockdown profoundly inhibits mTOR activity and cell proliferation in HUVEC revealing a previously unknown connection. Inhibition of VDAC1 by itraconazole leads to an increase in cellular AMP:ATP ratio and activation of the AMP-activated protein kinase (AMPK), an upstream regulator of mTOR. VDAC1-knockout cells are resistant to AMPK activation and mTOR inhibition by itraconazole, demonstrating that VDAC1 is the mediator of this activity. In their testing it was found that by using a phenotypical approach starting with the effect of itraconazole the G1-S cell cycle transition of the endothelial cells, itraconazole specifically inhibited the mTOR signaling pathway by downregulating the kinase activity of mTORC1.

Chow Et Al2 completed a study utilizing RNA sequencing to decipher the biological pathway propelling BCC growth. From the assay results, it was observed that BCCs exhibited a considerable amplification in the expression of the mTOR pathway. This pathway plays an essential role in regulating angiogenesis, the growth of new blood vessels from pre-existing ones. Thus, this indicates that it is the heightened activity of the mTOR pathway, and the consequent enhancement of angiogenesis, that stimulates the growth.

Data from Inhibitor’s completed Phase 2b SCORING Trial complements the literature with reference to the Lesion Response of the study which shows that across the 477 target lesions the investigators reported reductions of any size from baseline for 399 (83.65%) lesions, 64 (13.42%) had no change and 14 increased in size. A pre-determined reduction of 30% or greater was seen in 275 of the 477 (57.7%) target lesions, including 130 lesions which resolved completely (27.3%). A total of 13 new ‘surgically eligible’ lesions across 8 of the 38 patients developed over the duration of the study.

For more information about Inhibitor and our mission please visit us on our website (www.inhibitortx.com) and for any further or specific queries you may have please visit our contact us page, submit your details/query, and a representative will be happy to get in touch.

On December 13, 2023 Verastem Oncology (Nasdaq: VSTM) (the "Company"), a biopharmaceutical company committed to advancing new medicines for patients with cancer, reported that it has initiated its international confirmatory Phase 3 RAMP 301 trial (GOG-3097; ENGOT-ov81/NCRI), evaluating the combination of avutometinib and defactinib versus standard chemotherapy or hormonal therapy for the treatment of recurrent low-grade serous ovarian cancer (LGSOC) (Press release, Verastem, DEC 13, 2023, View Source [SID1234638536]).

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"Patients and treating physicians have advocated for more research and development in support of LGSOC. At Verastem Oncology, we are moving with urgency to offer a Phase 3 study specifically directed at this disease in an effort to address this need," said Dan Paterson, President and Chief Executive Officer, Verastem Oncology. "Based on our Breakthrough Therapy Designation, the initiation and expected progress of this trial, along with the FRAME study data and mature RAMP 201 data, we plan to file for Accelerated Approval in the first half of next year, moving us a significant step closer to addressing the treatment needs of patients living with LGSOC."

RAMP 301 is the confirmatory study required by the U.S. Food and Drug Administration (FDA) for the combination of avutometinib and defactinib to potentially receive full approval for the treatment of recurrent LGSOC. The Company intends to submit an Accelerated Approval New Drug Application (NDA) for the combination of avutometinib and defactinib based on mature data from the Company’s Phase 2 registration-directed RAMP 201 trial, together with the results of the investigator-initiated FRAME trial. The company recently reported results of Part A of the RAMP 201 trial, including confirmed objective response rates (ORR) by blinded independent central review of 45% with a response rate and safety profile consistent with previous studies.​

"LGSOC has a unique molecular, histologic, and clinical profile that differs dramatically from the most common type of ovarian cancer. Response rates to standard of care treatments are disappointing, and there are still no FDA approved treatments specifically for LGSOC," said Rachel Grisham, M.D., Section Head, Ovarian Cancer and Director, Gynecologic Medical Oncology at Memorial Sloan Kettering Cancer Center in Westchester, NY and RAMP 301 global lead investigator. "The combination of avutometinib and defactinib continues to show promise in recurrent LGSOC, and I am looking forward to leading this confirmatory trial with the goal of establishing a new standard of care for people with this rare form of ovarian cancer."

According to Professor Susana Banerjee, MBBS, MA, PhD, FRCP, Consultant Medical Oncologist and Research Lead for the Gynaecology Unit at The Royal Marsden NHS Foundation Trust, Team Leader in Women’s Cancers at The Institute of Cancer Research, London, and lead European investigator of the RAMP 301 trial, "Based on my experience treating women with LGSOC, it’s clear that we need better therapeutic options. I am pleased this Phase 3 trial, following the initial positive results from the Phase 2 RAMP 201 trial, is enrolling patients to potentially address the significant limitations we have seen with other available therapies."

RAMP 301 (GOG-3097; ENGOT-ov81/NCRI) is an international collaboration between The GOG Foundation, Inc. (GOG) and the European Network of Gynaecological Oncological Trial groups (ENGOT) sponsored by Verastem Oncology. The trial is expected to enroll 270 patients who will be randomized to either the combination of avutometinib and defactinib or investigator’s choice chemotherapy (pegylated liposomal doxorubicin, paclitaxel, topotecan) or hormone therapy (letrozole, anastrozole). The primary endpoint is progression free survival (PFS) by Blinded Independent Central Review. Secondary endpoints include ORR, duration of response​, disease control rate, safety and tolerability, patient reported outcomes, and overall survival. RAMP 301 is a global trial with enrollment open in the U.S. and planned enrollment in Canada, the United Kingdom, Europe, Australia, and Korea.

Dr. Grisham and Dr. Banerjee are paid consultants for Verastem Oncology.

About the Avutometinib and Defactinib Combination

Avutometinib is a RAF/MEK clamp that induces inactive complexes of MEK with ARAF, BRAF and CRAF potentially creating a more complete and durable anti-tumor response through maximal RAS pathway inhibition. In contrast to currently available MEK inhibitors, avutometinib blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows avutometinib to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other inhibitors. The U.S. Food and Drug Administration granted Breakthrough Therapy designation for the combination of Verastem Oncology’s investigational RAF/MEK clamp avutometinib, with defactinib, its FAK inhibitor, for the treatment of all patients with recurrent LGSOC regardless of KRAS status after one or more prior lines of therapy, including platinum-based chemotherapy.

Verastem Oncology is currently conducting clinical trials with its RAF/MEK clamp avutometinib in RAS pathway-driven tumors as part of its (Raf And Mek Program). RAMP 301 is a Phase 3 confirmatory trial evaluating the combination of avutometinib and defactinib versus standard chemotherapy or hormonal therapy for the treatment of recurrent LGSOC. RAMP 201 is a Phase 2 registration-directed trial of avutometinib in combination with defactinib in patients with recurrent LGSOC and has completed enrollment in the dose optimization and expansion phases and is enrolling for low-dose evaluation. Verastem Oncology has established clinical collaborations with Amgen and Mirati to evaluate LUMAKRAS (sotorasib) and KRAZATI (adagrasib) in combination with avutometinib in KRAS G12C mutant NSCLC as part of the RAMP 203 and RAMP 204 trials, respectively. Supported by the "Therapeutic Accelerator Award" Verastem Oncology received from PanCAN, the Company is conducting RAMP 205, a Phase 1b/2 clinical trial evaluating avutometinib and defactinib with gemcitabine/nab-paclitaxel in patients with front-line metastatic pancreatic cancer.

About Low-Grade Serous Ovarian Cancer (LGSOC)

LGSOC is a highly recurrent, chemotherapy-resistant cancer, associated with slow tumor growth and high mortality rate. Approximately 6,000 women in the U.S. and 80,000 worldwide are living with this disease. Mutations in the KRAS gene are present in 35-57% cases of LGSOC. LGSOC is most often diagnosed in women between the ages of 45-55 years and has a median survival of approximately ten years. The majority of patients experience severe pain and complications as the disease progresses. Chemotherapy is the standard of care for this disease, with limited treatment options currently available.

On December 13, 2023 Shattuck Labs, Inc. (Shattuck) (NASDAQ: STTK), a clinical-stage biotechnology company pioneering the development of bi-functional fusion proteins as a new class of biologic medicine for the treatment of patients with cancer and autoimmune disease, reported initial topline dose-expansion data from its ongoing Phase 1A/B clinical trial of SL-172154 in combination with AZA in frontline HR-MDS and TP53m AML patients (Press release, Shattuck Labs, DEC 13, 2023, View Source [SID1234638533]). Initial data from the dose-expansion cohorts build on the complete dose-escalation data featured in a poster presentation on December 11, 2023 at the 65th ASH (Free ASH Whitepaper) Annual Meeting.

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"Both the frontline HR-MDS and TP53m AML expansion cohorts enrolled quickly after completion of the dose escalation study in the middle of this year, and we are pleased to share initial efficacy data, which begin to demonstrate the activity of SL-172154 beyond what is expected of AZA alone. In dose escalation, we saw a monotherapy response to SL-172154 in a heavily pre-treated relapsed/refractory (R/R) TP53m AML patient that allowed the patient to receive a stem cell transplant. That patient remains disease free." said Dr. Lini Pandite, MBChB, M.B.A., Chief Medical Officer of Shattuck. "In frontline, the rate of complete responses in both the HR-MDS and TP53m AML cohorts is already encouraging, and when coupled with the observation of peripheral blood count recovery in most patients that have not yet achieved a complete response, and the fact that many of these patients are very early in their course of treatment and have not yet reached the median time at which a complete response is expected for azacitidine, suggests that the complete response rate may continue to improve in the coming months. As a result, we have amended both studies to increase the sample size and look forward to providing another update by mid-year 2024."

Phase 1B Trial of SL-172154 in Frontline TP53m AML and HR-MDS

Key takeaways: Early efficacy observed for SL-172154 in combination with AZA in previously untreated HR-MDS and TP53m AML:

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HR-MDS: In 14 evaluable patients with previously untreated HR-MDS (13 of whom had TP53m or deletion), five patients achieved a CR. Four patients achieved a mCR (3 with hematologic improvement in at least one lineage), and two patients achieved stable disease (both with hematologic improvement in at least one lineage).

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TP53m AML: In 11 evaluable patients with previously untreated TP53m AML, two patients achieved a CR. Another patient achieved a CRi and was taken to allogeneic hematopoietic cell transplantation (allo-HCT). Seven additional subjects with stable disease had blast reductions, five of which had recovery of platelets or neutrophils and remain on study and their response may improve. One subject died during the first cycle.

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Safety: Preliminary data suggest that SL-172154 has an acceptable safety and tolerability profile in combination with azacitidine.

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Data Overview: As of the data cut-off date of December 1, 2023, 14 frontline patients enrolled in the TP53m AML cohort, and 22 frontline patients enrolled in the HR-MDS cohort. Initial enrollment was completed in the fourth quarter of 2023 and Shattuck has elected to expand the cohorts with additional data expected mid-year 2024.

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Preliminary signs of anti-tumor activity: Early signals of activity, in the form of rapid blast count reductions, were observed in 100% of frontline TP53m AML patients treated with SL-172154 in combination with AZA who received an on-treatment bone marrow biopsy. Most patients in the HR-MDS cohort showed blast count reductions with hematologic improvement early in the treatment course.

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SL-172154 had an acceptable safety and tolerability profile: Infusion-related reactions (IRRs) were the most common SL-172154 related treatment-emergent adverse events (TEAEs).

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In the TP53m AML and HR-MDS cohorts, IRRs were reported in seven patients (50%) and seven patients (32%) respectively.

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Grade 3 or 4 AEs related to SL-172154 were reported in two patients (14%) in TP53m AML and four patient (18%) in HR-MDS, including IRR (2), increased AST (1), increased ALT (1), fatigue (1), hypoxia (1), pneumonia (1), chondrocalcinosis (1), and febrile neutropenia (1). There were no reports of destructive anemia.

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In the TP35m AML expansion cohort, there was one Grade 5 AE of cardiac arrest reported in one patient with history of coronary artery disease, recent arrhythmia, and hypokalemia in the setting of amiodarone use. In the HR-MDS cohort, there were no Grade 5 AEs related to SL-172154 reported.

Phase 1A Trial of SL-172154 in R/R AML and HR-MDS and Frontline TP53m HR-MDS

A copy of the ASH (Free ASH Whitepaper) presentation, titled "Safety, Pharmacodynamic, and Anti-Tumor Activity of SL-172154 as Monotherapy and in Combination with Azacitidine (AZA) in Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) and Higher-Risk Myelodysplastic Syndromes/neoplasms (HR-MDS) Patients (pts)," is accessible under posters in the "Our Science" section of Shattuck’s website.

Key takeaways: Anti-tumor responses were observed as monotherapy and in combination with AZA. SL-172154 alone and in combination with AZA had an acceptable safety profile, consistent with the safety profile of the individual agents (see SL-172154 safety above). No destructive anemia was observed.

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Data Overview: As of the data cut-off date of September 15, 2023, 32 adult patients with R/R AML and HR-MDS received SL-172154 as monotherapy or in combination with AZA in the parallel staggered dose-escalation portion of a Phase 1A/B clinical trial. Patients had a median of two prior lines of therapy. An additional five subjects with frontline TP53m HR-MDS received SL-172154 with AZA.

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Preliminary signs of anti-tumor activity: Monotherapy response in a R/R AML patient and early signals of anti-leukemic activity (in the form of blast count reductions) in patients with R/R AML who received SL-172154 in combination with AZA were observed in a dose-dependent manner.

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SL-172154 monotherapy activity (Morphologic Leukemia-Free State) was observed in a heavily pretreated R/R AML patient and subsequently proceeded to allo-HCT.

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Patient achieved MLFS (blast reduction from 19% to <5%) after one cycle of SL-172154.

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Anti-tumor activity was also observed in combination with AZA in previously untreated TP53m HR-MDS patients. Out of four evaluable previously untreated TP53m HR-MDS patients, there was one CR and one mCR. One patient with mCR and one patient with SD proceeded to allo-HCT. The patient in a CR remains in a CR long term.

Conference Call at 8:00 a.m. ET Today

Shattuck will host a conference call today at 8:00 a.m. ET featuring key opinion leader Dr. Naval Daver, MD, (Professor, Director Leukemia Research Alliance Program, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX) to present the initial data from the frontline expansion cohorts in HR-MDS and TP53m AML. Additionally, a review of data from the poster presentation featured at the 65th ASH (Free ASH Whitepaper) Annual Meeting will be discussed. To listen to the live webcast, please visit the Investor Relations page of the Shattuck Labs website here. Participants may register for the call here. While not required, interested participants are encouraged to join 10 minutes prior to the start of the event.

A replay of the webcast will be available following the conclusion of the live call and will be accessible on the Company’s website.

About SL-172154

SL-172154 (SIRPα-Fc-CD40L) is an investigational ARC fusion protein designed to simultaneously inhibit the CD47/SIRPα checkpoint interaction and activate the CD40 costimulatory receptor to bolster an anti-tumor immune response in patients with advanced cancer. Multiple Phase 1 clinical trials are ongoing for patients with PROC (NCT04406623, NCT05483933) and patients with AML and HR-MDS (NCT05275439).

On December 13, 2023 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS’’ or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, reported that it will host a corporate update webinar on Wednesday, January 3, 2024, at 8:30 a.m. Eastern Time (Press release, Sellas Life Sciences, DEC 13, 2023, View Source [SID1234638532]).

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Angelos Stergiou, MD, ScD h.c., President and Chief Executive Officer of SELLAS, will discuss the Company’s achievements in 2023 and provide an outlook for 2024. Dr. Stergiou will be joined by two key opinion leaders and principal investigators who will discuss the Phase 3 registrational REGAL clinical trial of galinpepimut-S (GPS) in patients with acute myeloid leukemia and the clinical program for SLS009, the Company’s CDK9 inhibitor:

Dr. Panagiotis Tsirigotis, Professor of Hematology, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
Dr. Tapan Kadia, Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center, Houston, Texas
To access the webinar, please use the following information:

Date: Wednesday, January 3, 2024
Time: 8:30 a.m. Eastern Time
Dial-in (U.S.): 1-877-423-9813
International Dial-in: 1-201-689-8573
Webcast: SELLAS Update Call

On December 13, 2023 Propanc Biopharma, Inc. (OTC Pink: PPCB) ("Propanc" or the "Company"), a biopharmaceutical company developing novel cancer treatments for patients suffering from recurring and metastatic cancer, reported that the Company’s joint researcher, Mrs. Belén Toledo Cutillas, has commenced an internship at the Cancer Center Amsterdam – vUMC (University Medical Centers). In addition to Propanc Biopharma providing the financial resources to develop PRP, funding from two international grants has enabled Mrs. Toledo to join the Molecular Oncology Laboratory at the Cancer Center Amsterdam. Research by this team of scientists, led by Professor Elisa Giovanetti, focuses on chemotherapy resistance in pancreatic cancer (Press release, Propanc, DEC 13, 2023, View Source [SID1234638531]).

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"Chemotherapy is still considered an irreplaceable front-line therapeutic strategy to treat cancer. But multidrug resistance represents a common hurdle that profoundly compromises clinical outcomes, especially in pancreatic cancer. It is key to identify new drugs that could reduce chemoresistance and thus combat tumors with existing treatments," said Mrs. Toledo. The preclinical research undertaken by Mrs. Toledo at the Cancer Center Amsterdam focuses on the effects of pancreatic proenzyme formulation (PRP) on a panel of chemoresistant cancer cell lines that had previously been established in Professor Giovanetti’s lab.

"We wanted to evaluate the effect of PRP in the widest range of pancreatic cancer cell lines to gain a better idea how this treatment may affect actual tumors," said Mrs. Toledo. "So far, we have obtained very promising results. PRP seems not only to reduce chemoresistance of pancreatic tumor cells, but also appears to alter the tumor microenvironment."

Dr Julian Kenyon, MD, MB, ChB, Propanc’s Chief Scientific Officer said, "We are pleased to continue to drive success through our joint research partners, and Belén’s investigation into the effects of PRP as a chemosensitizing agent has significant implications for the planned clinical development of PRP as a novel therapy for the treatment and prevention of metastatic cancer. Tumor resistance to frontline chemotherapy means a poor prognosis for survival, especially in pancreatic cancer. We look forward to investigating the clinical effects of PRP in patients as we progress with future planned clinical trials, where an opportunity for a combinatorial therapeutic strategy may be uncovered to treat resistant tumors."

PRP is a mixture of two proenzymes, trypsinogen and chymotrypsinogen from bovine pancreas, administered by intravenous injection. A synergistic ratio of 1:6 inhibits growth of most tumor cells. Examples include pancreatic, ovarian, kidney, breast, brain, prostate, colorectal, lung, liver, uterine, and skin cancers. Orphan Drug Designation status of PRP has been granted from the US Food and Drug Administration (FDA) for treatment of pancreatic cancer.

For a full transcript of the interview with Mrs. Belén Toledo Cutillas, please click the following link: View Source