On September 23, 2024 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting hard-to-treat tumors and viruses, reported the recent presentation of positive in vivo efficacy data of Annamycin in orthotopic and experimental lung metastatic models of sarcoma (Press release, Moleculin, SEP 23, 2024, View Source [SID1234646822]).

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The poster titled "Annamycin: Opening New Doors for Organotropic Targeting of Primary and Metastatic Lung Cancer," authored by Waldemar Priebe, PhD (Founder, Founding Scientist, and Chair of Scientific Advisory Board for Moleculin) and coworkers was recently presented at the IASLC 2024 World Conference on Lung Cancer. The presented poster outlined results from the efficacy assessment studies of Annamycin, Moleculin’s next-generation anthracycline in orthotopic models of lung cancer and sarcoma lung metastasis models in comparison with doxorubicin (a commonly prescribed anthracycline).

"Annamycin continues to exhibit consistent activity against different type of cancers including therapy resistant cancers such as soft tissue sarcoma lung metastases while also avoiding cardiotoxicity, which continues to be a significant side effect limiting the clinical use of anthracyclines. Importantly, the presented data demonstrates that treatment with Annamycin results in statistically significant inhibition of tumor growth and extension of survival in orthotopic lung cancer models, which is consistent with the preliminary results we are seeing in our sarcoma clinical trials. This further underscores Annamycin’s potential to provide a much-needed treatment option for patients with primary or metastatic lung cancers, as a single agent and in combination with currently used therapeutics. Combined with the encouraging growing body of clinical data from our ongoing studies, we remain confident in Annamycin’s potential to address significant unmet needs in a wide range of cancers," commented Walter Klemp, Chairman and Chief Executive Officer of Moleculin.

Key Highlights

Annamycin demonstrated high uptake and retention in lung parenchyma of mice and rats.
The therapeutic effects of doxorubicin (DOX) are diminished due to low lung DOX uptake as demonstrated in the tested in vivo models. In contrast, Annamycin exhibits consistent efficacy in vivo in orthotopic and experimental lung metastatic models of sarcoma, breast, and colon cancer. This correlated with high Annamycin concentration in lungs, which exceeded DOX levels by 10- to 30-fold.
Preclinical tests clearly demonstrate a better cardiac safety profile of Annamycin when compared to DOX and no cardiotoxicity of Annamycin in the in vivo models. No cardiotoxicity of Annamycin has been noted in ongoing clinical studies.
The observed organotropic properties of Annamycin, its efficacy in vivo, and its promising safety profile warrant further translational studies to evaluate Annamycin in patients with primary or metastatic lung cancers, as a single agent and in combination with currently used therapeutics.
Annamycin is currently being evaluated in ongoing clinical trials for the treatment of relapsed or refractory acute myeloid leukemia (AML) and soft tissue sarcoma (STS) lung metastases. Annamycin currently has Fast Track Status and Orphan Drug Designation from the FDA for the treatment of relapsed or refractory acute myeloid leukemia, in addition to Orphan Drug Designation for the treatment of soft tissue sarcoma. Furthermore, Annamycin has Orphan Drug Designation for the treatment of relapsed or refractory acute myeloid leukemia from the European Medicines Agency (EMA).

On September 23, 2024 Kazia Therapeutics Limited (NASDAQ: KZIA), an oncology-focused drug development company, reported the presentation of data highlighting promising clinical activity of EVT801 in high grade serous (HGS) Ovarian Cancer at the 15th Biennial Ovarian Cancer Research Symposium, co-presented by American Association of Cancer Research (AACR) (Free AACR Whitepaper) and the Rivkin Center for Ovarian Cancer Research on Saturday, September 21, 2024 in Seattle Washington (Press release, Kazia Therapeutics, SEP 23, 2024, View Source [SID1234646821]).

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Dr. John Friend, CEO Kazia Therapeutics presented preliminary data from a Phase 1 first-in-human clinical trial evaluating the safety and tolerability of EVT801, a highly selective small molecule VEGFR3 inhibitor targeting tumour angiogenesis. The Phase 1 study met its primary objectives, with the maximal tolerated dose identified at 500mg twice a day (BID). The Phase 1 study also identified the recommended Phase 2 dose starting at 400mg BID. It was observed that EVT801 was tolerated across all doses, with the majority of toxicities being mild to moderate and transient in nature.

Key points of the presentation included:

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A total of 26 patients were treated across 6 dosing cohorts ranging from 50mg once daily (QD) to 500mg twice daily (BID)

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Patients with eleven different cancer types (ex. colon, renal cell, pancreatic) were enrolled in the study, with heavily pretreated advanced ovarian cancer being the most prevalent indication (11 patients)

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Biomarkers have shown strong VEGFR3 expression in multiple indications, including ovarian cancer

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Encouraging clinical activity in High Grade Serous ovarian cancer patients with forty-six percent (46%) having stable disease or for at least three cycles, including two patients who received 9 cycles

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One patient had a partial response (-39% decrease) after 2 cycles of EVT801 therapy

Dr John Friend, CEO of Kazia Therapeutics, commented: "I was honored to participate at the Ovarian Cancer Research Symposium and present our findings to fellow clinicians and ovarian cancer researchers from around the globe. Ovarian cancer is often diagnosed at late stages with poor patient prognosis, so the data from the Phase 1 study is extremely encouraging and gives us confidence that we could potentially have a first-in-class VEGFR-3 inhibitor with EVT801."

Abstract: Phase I study of EVT801, a VEGFR-3 inhibitor, shows promising clinical activity in HGS ovarian cancer

View Source

September 21, 2024 – 11:30am-1:30pm

On September 23, 2024 Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) ("Innate" or the "Company") reported that the U.S Food and Drug Administration (FDA) has cleared its investigational new drug (IND) application to initiate a Phase 1 clinical study of IPH4502, its novel and differentiated topoisomerase I inhibitor antibody drug conjugate (ADC) targeting Nectin-4 in solid tumors. Innate expects to initiate the Phase 1 study in the coming months (Press release, Innate Pharma, SEP 23, 2024, View Source [SID1234646820]).

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The Phase 1, open-label, multi-center study, includes a Part 1 Dose Escalation and a Part 2 Dose Optimization, and will assess the safety, tolerability, and preliminary efficacy of IPH4502 as a single agent in advanced solid tumors known to express Nectin-4, including but not limited to urothelial carcinoma, non-small cell lung, breast, ovarian, gastric and colorectal cancers.

"We are thrilled to advance the IPH4502 program, and the IND application acceptance is an important milestone for Innate, as this is our first ADC program to enter the clinic," said Dr Sonia Quaratino, Chief Medical Officer of Innate Pharma. "IPH4502 is a novel and differentiated Nectin-4 ADC that has the potential to provide a new therapeutic option for patients with a cancer expressing a wide range of Nectin-4. Through this Phase 1 study we aim to advance the research on our ADC technology for the benefit of patients."

About IPH4502

IPH4502 is a novel topoisomerase I inhibitor Antibody Drug Conjugate (ADC) conjugated to exatecan targeting Nectin-4.

Nectin-4 is a cell membrane adhesion protein overexpressed in several solid tumors, including urothelial, breast, esophageal, lung, ovarian, and pancreatic cancers, with limited expression in normal tissues.

In non-clinical models, IPH45 was well tolerated and shows anti-tumor efficacy in vitro and in vivo.

On September 23, 2024 IDEAYA Biosciences, Inc. (the "Company") reported interim clinical data for darovasertib in neoadjuvant uveal melanoma ("UM") from the Company’s ongoing company-sponsored Phase 2 trial and guidance from the U.S. Food and Drug Administration ("FDA") in a Type C meeting, which the Company believes supports the initiation of a potential registration-enabling Phase 3 randomized clinical trial in neoadjuvant UM patients (Press release, Ideaya Biosciences, SEP 23, 2024, View Source [SID1234646819]).

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Darovasertib is a potent and selective protein kinase C ("PKC") inhibitor being developed to broadly address primary and metastatic UM. Darovasertib is currently being evaluated in four ongoing clinical trials, two of which are in collaboration with Pfizer. The darovasertib and crizotinib combination in metastatic uveal melanoma ("MUM") has FDA Fast Track designation. IDE196-009 (NCT05907954) is a company-sponsored Phase 2 trial evaluating darovasertib as neoadjuvant treatment for UM prior to primary interventional treatment of enucleation or radiation therapy, and as adjuvant therapy following the primary treatment. In addition, there is an investigator-sponsored trial ("IST"), NCT05187884, evaluating darovasertib as a neoadjuvant UM treatment.

The Phase 2 darovasertib data in neoadjuvant UM demonstrated encouraging clinical activity. Collectively with the IST trial, the clinical efficacy data from the Phase 2 company-sponsored trial substantiate clinical proof of concept for the use of darovasertib in the neoadjuvant uveal melanoma setting. For the Phase 2 company-sponsored trial, the data cutoff date is August 15, 2024, with an enrollment cut-off of May 13, 2024.

The Company evaluated 31 enucleation and 18 plaque brachytherapy UM patients who were treated with darovasertib neoadjuvant therapy in the Phase 2 company-sponsored and IST trials. The Company observed approximately 59%, or 29 of the 49 total evaluable patients, with greater than or equal to 20% ocular tumor shrinkage by product of diameters and approximately 49%, or 24 of the 49 total evaluable patients, with greater than or equal to 30% ocular tumor shrinkage by product of diameters. The Company also observed an approximately 61% eye preservation rate in enucleation patients. The Company found evidence of visual preservation by reducing the amount of radiation associated with plaque brachytherapy.

The Company observed manageable adverse event ("AE") profile from the Phase 2 company-sponsored trial. In 38 patients, 11% of patients experienced a Grade 3 or higher AE and 5% of patients experienced a serious AE rate. The Company observed a discontinuation rate of 3%. The most common AEs observed included diarrhea, nausea, vomiting and fatigue.

The Company’s ocular oncology advisory board recommended product of diameters for tumor measurement to determine overall response rate ("ORR") criteria in ocular melanoma. In the Phase 2 trial with darovasertib, a greater than or equal to 20% ocular tumor shrinkage by product of diameters correlates to clinical benefit, including eye sparing for enucleation UM patients and visual preservation for plaque brachytherapy UM patients.

In the Phase 3 clinical trial, the Company currently projects approximately 400 patients will be randomized for treatment with darovasertib in the treatment arm or the control arm, with potential modifications pending further feedback from the FDA. Based on the currently targeted clinical trial design, there will be two cohorts enrolled, including enucleation eligible UM patients and plaque brachytherapy eligible UM patients. For the enucleation cohort, the randomization will be with or without darovasertib as neoadjuvant therapy. For the plaque brachytherapy cohort, the randomization will be darovasertib followed by plaque brachytherapy versus plaque brachytherapy alone.

Based on FDA guidance and information provided in the Company’s FDA briefing book, the Company expects that eye preservation rate will be the primary endpoint for enucleation UM patients for the target registrational trial design in neoadjuvant UM. The FDA briefing book noted an objective to exceed lower bound of 10% eye preservation rate with a 95% confidence interval for this primary endpoint. Time to vision loss will be the primary endpoint for plaque brachytherapy UM patients. No detriment to Event-Free-Survival ("EFS") in the treatment arms will be a secondary endpoint.

Pending ongoing discussions with the FDA, the Company currently expects that ORR will be included as a potential surrogate and composite endpoint to support earlier approval scenarios. The FDA briefing book noted that a greater than or equal to 20% ocular tumor shrinkage by product of diameters correlates to clinical benefit in the ongoing Phase 2 clinical study, including eye sparing for enucleation UM patients and visual preservation for plaque brachytherapy UM patients. The registrational study will enroll UM patients with a high risk for metastatic disease. Based on the FDA meeting, there is a potential for consideration of a broad indication label in neoadjuvant UM for subjects with low, intermediate and high risk for metastatic disease. The Company anticipates approximately two years of data maturity to initial readout for no detriment to EFS in the treatment arms for this high-risk patient population based on preliminary projections. 300mg BID darovasertib was noted in the FDA briefing book as the move-forward dose for the registrational trial.

Neoadjuvant UM represents a significant expansion opportunity for darovasertib, with a potential annual incidence of approximately 12,000 patients aggregate in North America, Europe, and Australia. The Company owns or controls all commercial rights in darovasertib, including in MUM and in UM, subject to certain economic obligations pursuant to its exclusive, worldwide license with Novartis.

On September 23, 2024 Heidelberg Pharma AG (FSE: HPHA), a clinical stage company developing innovative Antibody Drug Conjugates (ADCs), reported that new data from its Phase I/IIa clinical study with lead Amanitin-based ADC candidate, HDP-101, will be presented at the 21st International Myeloma Society (IMS) Annual Meeting, being held in Rio De Janeiro, Brazil on 25 to 28 September 2024 (Press release, Heidelberg Pharma, SEP 23, 2024, View Source [SID1234646818]).

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HDP-101 is an Anti-BCMA antibody-Amanitin drug conjugate for the treatment of relapsed or refractory multiple myeloma, a bone marrow cancer with a high unmet medical need. Phase I of the trial is a dose escalation study to determine an optimal and safe dose level of HDP-101 in patients in preparation for Phase II clinical studies.

Professor Marc-Steffen Raab, Head of the Myeloma Center at the University Hospital Heidelberg and clinical investigator of the study will present new clinical findings from five patient cohorts of the ongoing open-label, multicenter Phase I/IIa trial evaluating HDP-101 in multiple myeloma.

Details of the presentation are as follow:

Presentation title: The Anti-BCMA Antibody-Drug Conjugate HDP-101 with a Novel Amanitin Payload Shows Promising Initial First in Human Results in Relapsed Multiple Myeloma (OA – 60)

Session:

Abstract Session 5

Speaker:

Professor Marc-Steffen Raab

Date and time:

Friday, 27 September 2024, 9:48 am – 10:00 am (BRT)

Location:

Plenary Hall, Pavilion 3; Room name: 101 A1-A2

Previous data from cohort five have demonstrated biological activity in three out of five patients, and an objective improvement in disease was detected ("partial remission"). The trial is currently treating patients in its sixth cohort with further data to be presented at upcoming scientific conferences.

Following the presentation at IMS, Heidelberg Pharma will host a R&D Webinar on 15 October 2024 at 17:00 pm CEST/ 11:00 am ET, for investors, analysts and media. Further registration information will be announced in due course.