On June 10, 2024 Lixte Biotechnology Holdings, Inc. (the "Company") reported to have entered into a Clinical Trial Agreement (the "Agreement") with the Netherlands Cancer Institute ("NKI") to conduct a Phase 1b/2 clinical trial of the Company’s protein phosphatase inhibitor, LB-100, combined with atezolizumab, a PD-L1 inhibitor, the proprietary molecule of F. Hoffman-La Roche Ltd. ("Roche"), for patients with metastatic colon cancer (Filing, 8-K, Lixte Biotechnology, JUN 10, 2024, View Source [SID1234644326]). Under the Agreement, the Company will provide its lead compound, LB-100, and under a separate agreement between NKI and Roche, Roche will provide atezolizumab and financial support for the clinical trial. The Company has no obligation to, and will not provide any reimbursement of clinical trial costs. Pursuant to the Agreement and the protocol set forth in the Agreement, the clinical trial will be conducted by NKI at NKI’s site in Amsterdam by principal investigator Neeltje Steeghs, MD, PhD, and NKI will be responsible for the recruitment of patients. The Agreement provides for the protection of the respective intellectual property rights of each of the Company, NKI and Roche.

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This Phase 1b clinical trial will evaluate the side effects and optimal dose of LB-100 combined with atezolizumab for the treatment of patients with metastatic microsatellite stable colorectal cancer. Immunotherapy using monoclonal antibodies like atezolizumab can enhance the body’s immune response against cancer and hinder tumor growth and spread. LB-100 has been found to improve the effectiveness of anticancer drugs in killing cancer cells by inhibiting a protein called PP2A on cell surfaces. Blocking PP2A increases stress signals in tumor cells expressing the PP2A protein. Accordingly, combining atezolizumab with LB-100 may enhance treatment efficacy for metastatic colorectal cancer, as cancer cells with heightened stress signals are more vulnerable to immunotherapy.

This study comprises a dose escalation phase and a dose expansion phase. The objective of the dose escalation phase is to determine the recommended Phase 2 dose (RP2D) of LB-100 when combined with the standard dosage of atezolizumab. The dose expansion phase will further investigate the clinical activity, safety, tolerability, and pharmacokinetics/dynamics of the LB-100 and atezolizumab combination. The clinical trial is scheduled to open by June 30, 2024. Patient accrual is expected to take up to 24 months, with a maximum of 37 patients with advanced colorectal cancer to be enrolled in this study.

Additional information on the clinical trial is available on the clinicaltrials.gov website at View Source

The foregoing description of the terms of the Agreement does not purport to be complete and is subject to and qualified in its entirety by reference to the Agreement, a copy of which is filed with this Form 8-K and incorporated by reference.

On June 10, 2024 Sermonix Pharmaceuticals Inc., a privately held biopharmaceutical company developing innovative therapeutics to specifically treat metastatic breast cancers (mBC), reported the publication of its scholarly article, "Lasofoxifene as a Potential Treatment for Aromatase Inhibitor-Resistant ER-Positive Breast Cancer," in the peer-reviewed journal Breast Cancer Research (Press release, Sermonix Pharmaceuticals, JUN 10, 2024, View Source [SID1234644286]). The paper discusses positive findings observed during a preclinical study examining the effects of oral lasofoxifene, Sermonix’s lead investigational drug, on aromatase inhibitor-resistant, estrogen receptor-positive (ER+) breast cancer in the absence of ESR1 mutations.

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The study investigated the activity of lasofoxifene in a letrozole-resistant breast tumor model that did not have ESR1 mutations. Letrozole-resistant, MCF7 LTLT cells tagged with luciferase-GFP were injected into the mammary duct inguinal glands of NSG mice (MIND model; 6 mice/group). The mice were randomized to vehicle – lasofoxifene alone or plus palbociclib, fulvestrant alone or plus palbociclib, or palbociclib alone – two to three weeks after cell injections. Tumor growth and metastases were monitored with in vivo and ex vivo luminescence imaging, terminal tumor weight measurements and histological analysis. The experiment was repeated with the same design and eight to nine mice in each treatment group.

Western blot analysis showed that the MCF7 LTLT cells had lower ERα and higher HER2 expressions compared with normal MCF7 cells. Lasofoxifene alone or combined with palbociclib, but not fulvestrant, significantly reduced primary tumor growth versus vehicle as assessed by in vivo imaging of tumors at study ends. Percent tumor area in excised mammary glands was significantly lower for lasofoxifene plus palbociclib versus vehicle. Ki67 staining showed decreased overall tumor cell proliferation with lasofoxifene alone or combined with palbociclib. The lasofoxifene plus palbociclib combination was also associated with significantly fewer bone metastases compared with vehicle. Similar results were observed in the repeat experiment.

"We previously demonstrated that lasofoxifene effectively inhibits breast tumor growth in tumors bearing an ESR1 mutation that are resistant to endocrine therapy," said Dr. Geoffrey Greene, M.D., Ph.D., chair of the Ben May Department for Cancer Research at the University of Chicago. "In this aromatase-resistant breast tumor model, we now show that lasofoxifene inhibits tumor growth in the absence of an ESR1 mutation and with low ESR1 expression, suggesting that lasofoxifene can be an effective therapy option for all hormone-treatment resistant breast tumors."

Evidence of lasofoxifene’s antitumor activity in breast cancers with ESR1 mutations was previously demonstrated during the first two Evaluation of Lasofoxifene in ESR1 Mutations (ELAINE) trials. During ELAINE-1, lasofoxifene as a monotherapy led to numerically longer progression-free survival than fulvestrant (5.6 vs. 3.7 months; P=0.138) in patients with endocrine therapy-resistant, ESR1-mutated mBC who had prior CDK4/6i exposure. In ELAINE-2, the combination of lasofoxifene and abemaciclib was associated with a median progression-free survival of approximately 13 months.

ELAINE-3, A global registrational Phase 3 study, is currently enrolling, with clinical trial sites across the U.S., Europe, Asia-Pacific, Israel and Canada. ELAINE-3 is assessing the efficacy of oral lasofoxifene and Eli Lilly and Company’s CDK4/6 inhibitor abemaciclib (Verzenio) compared to fulvestrant and abemaciclib in 400 pre- and post-menopausal subjects with locally advanced or metastatic ER+/HER2- breast cancer with an ESR1 mutation.

"The results of this new study demonstrate, for the first time, lasofoxifene’s anti-tumor activity in mouse models of ER-resistant breast cancer in the absence of ESR1 mutations, broadening its potential to become a valuable therapy regardless of ESR1 status," said Barry Komm, Ph.D., Sermonix chief scientific officer and co-author of the article. "As we remain focused on completing the ELAINE-3 trial, we are excited to further examine this new avenue of investigation and the potentially broader promise of lasofoxifene."

The open-access paper can be accessed online here.

On June 10, 2024 Defence Therapeutics Inc. ("Defence" or the "Company"), (CSE: DTC, OTCQB: DTCFF, FSE: DTC), a Canadian biopharmaceutical company developing novel immune-oncology vaccines and drug delivery technologies, reported its participation to the Society of Nuclear and Molecular Imaging ("SNMMI") annual meeting on June 11, 2024 at the Metro Toronto Convention Centre (Press release, Defence Therapeutics, JUN 10, 2024, View Source;utm_medium=rss&utm_campaign=defence-to-participate-to-2024-society-of-nuclear-medicine-and-molecular-imaging-annual-meeting-in-toronto-on-june-11-2024 [SID1234644251]).

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The SNMMI is a nonprofit scientific and professional organization that promotes the science, technology and practical application of nuclear medicine and molecular imaging. SNMMI strives to be a leader in unifying, advancing, and optimizing molecular imaging and radiotherapy, with a goal of improving human health. With 13,000 members worldwide, SNMMI represents nuclear and molecular imaging professionals, all of whom are committed to the advancement of the field. The SNMMI Annual Meeting is recognized as the premier educational, scientific, research, and networking event in nuclear medicine and molecular imaging. The event provides physicians, technologists, pharmacists, laboratory professionals, and scientists with an in-depth view of the latest research and development in the field as well as providing insights into practical applications for the clinic. SNMMI conference is the most recognized worldwide conference in the field of radiotherapy and molecular imaging gathering the most prestigious leader.

Defence is developing in collaboration with Orano Support SAS, a novel Radio-Immuno-Conjugate ("RIC"), named AccuTRICTM, which includes Defence’s AccuTOX resulting in increase efficacy to treat hard-to-treat cancers. The objective of this project is to develop the next generation of RIC exploiting the therapeutic dependency of Auger electron ("AE") emitter elements in closer proximity to DNA when combined with Defence’s Accum technology to induce its nuclear accumulation. AE emitters are very promising radionuclides for radiotherapy because of their very short pathlength radiation deposition, which decreases radiotoxicity on healthy tissues. The Accum moiety can overcome major limitations of RIC e.g. endosomal sequestration and poor nuclear accumulation, by destroying endosome membrane without affecting the plasma membrane nor mAbs specificity. Defence has developed a multitude of Accum variants with different biochemical properties and activities such as charged, hydrophobicity and cytotoxicity. One of these molecules is Defence’s lead molecule AccuTOX. AccuTRICTM is the combination of the synergistic activity of AccuTOX and the radiotherapeutics potential of AE. Defence’s AccuTRICTM objective is to efficiently treat hard-to-treat cancers with the potential of opening a new cancer therapy market based on a very promising radiotherapeutics implicating AE emitter radionuclides.

On June 10, 2024 Diakonos Oncology Corporation ("Diakonos"), a clinical stage immuno-oncology company, reported that it will present at the Emerging Growth Conference on Wednesday, June 12 (Press release, Diakonos Oncology, JUN 10, 2024, View Source [SID1234644241]). The company’s presentation, including Q&A, will run from 1:10 pm -1:40 pm Eastern time.

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This live, interactive online event will give existing shareholders and the investment community an introduction to the company and an update of recent clinical data highlights and corporate progress. The company’s CFO, Anthony Baldor, will present, with a short Q&A to follow. Questions may be submitted in advance of the event to [email protected], or during the event through the Emerging Growth Conference presentation platform.

Participants are invited to register at the following link to ensure they will be able to attend the conference and receive any updates that are released: View Source;tp_key=76d4029138&sti=diakonos

If attendees are not able to join the event live on the day of the conference, an archived webcast will also be made available on EmergingGrowth.com and on the Emerging Growth YouTube Channel, View Source A video link will be released after the event.

About the Emerging Growth Conference

The Emerging Growth conference is an effective way for public and private companies to present and communicate key events, progress and other major announcements to the investment community on a convenient and interactive virtual platform, in real time.

The Conference focus and coverage includes companies in a wide range of growth sectors, with strong management teams, innovative products and services, focused strategy, execution, and the overall potential for long term growth. Its audience includes tens of thousands of Individual and Institutional investors, as well as investment advisors and analysts.

All sessions will be conducted through video webcasts and will take place in the Eastern time zone.

On June 10, 2024 Almirall, a global pharmaceutical company dedicated to medical dermatology, reported that the U.S. Food and Drug Administration (FDA) has approved Almirall’s recent supplemental New Drug Application (sNDA) to expand the use area for its drug, Klisyri, to up to 100 cm (Press release, Almirall, JUN 10, 2024, View Source [SID1234644240]). Klisyri, a microtubule inhibitor ointment, is now approved in a 350 mg package size and is a 5-day topical field treatment for actinic keratosis (AK) of the face or scalp.

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"The FDA’s approval of the use of Klisyri for actinic keratosis on an extended surface of the face or scalp is a significant step forward for both patients and treating dermatologists. With patients experiencing AK over larger surface areas, dermatologists are looking for ways to treat the entire affected area to help prevent further lesion progression," says Karl Ziegelbauer, Chief Scientific Officer at Almirall.

This new approval will change the previous Klisyri (tirbanibulin) dosing for surface area treatment from up to 25 cm2 to up to 100 cm2, allowing clinicians to treat a larger area of the face or balding scalp. The sNDA was supported by an additional Phase 3, multicenter, open-label, clinical safety study with more than 100 patients in the US. The primary endpoints of the study were to evaluate the safety and tolerability of applying tirbanibulin to a field of approximately 100 cm2 on the face or balding scalp of adult AK patients. The study showed consistent results with the original pivotal trials conducted on an area of 25 cm2, for both local skin reactions and treatment related adverse events (AEs).

The effectiveness of tirbanibulin in a larger treatment area was also explored, showing a percent reduction in AK lesion count in line with the one reported in the original pivotal studies.

"With this new FDA approval, clinicians can now treat up to four times the surface area, allowing increased flexibility to provide treatment of actinic keratoses and achieve effective results with a good safety and tolerability profile for more patients," says Neal Bhatia, MD, from San Diego, CA, who served as the principal investigator for the larger treatment area pivotal study.

Klisyri will be available in two package sizes, 250 mg (NDC 16110-391-05) for the treatment of up to 25 cm2, and 350 mg (NDC 16110-391-55)] for up to 100 cm2.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Ophthalmic Adverse Reactions
Klisyri may cause eye irritation. Avoid transfer of the drug into the eyes and to the periocular area during and after application. Wash hands immediately after application. If accidental exposure occurs, instruct patient to flush eyes with water and seek medical care as soon as possible.

Local Skin Reactions
Local skin reactions, including severe reactions (erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration) in the treated area can occur after topical application of Klisyri. Avoid use until skin is healed from any previous drug, procedure, or surgical treatment. Occlusion after topical application of Klisyri is more likely to result in irritation.

ADVERSE REACTIONS
The most common adverse reactions (incidence ≥2%) were local skin reactions, application site pruritus, and application site pain.

Click here to view Full Prescribing Information.

About Klisyri: Klisyri tirbanibulin ointment, 1% is a novel microtubule inhibitor indicated for the topical field treatment of actinic keratosis (AK) of the face or scalp. Klisyri has a demonstrated efficacy and safety profile, and a convenient 5-day application period, which is the shortest of any topical treatment for AK.1

About Actinic Keratosis: Actinic keratosis or solar keratosis is a chronic and precancerous skin disease that occurs primarily in areas that have been exposed to ultraviolet (UV) radiation for a long period of time. It is usually found on the face, ears, lips, bald scalp, forearms, the posterior part of the hands, and lower legs. It is not possible to predict which AK lesions will develop into squamous cell carcinoma, so all lesions should be treated by a dermatologist. Actinic keratosis is the most common pre-cancerous dermatological condition. AK is the second most common diagnosis made by dermatologists in the United States.2 The reported prevalence of AK is between 11% and 25%.