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 Royalty Pharma plc (the "Issuer") reported offering of $500 million aggregate principal amount of 5.150% Senior Notes due 2029 (the "2029 Notes"), $500 million aggregate principal amount of 5.400% Senior Notes due 2034 (the "2034 Notes") and $500 million aggregate principal amount of 5.900% Senior Notes due 2054 (the "2054 Notes" and, together with the 2029 Notes and the 2034 Notes, the "Notes") (Filing, 8-K, Royalty Pharma , JUN 10, 2024, View Source [SID1234644224]). The Notes were issued under the indenture (the "Base Indenture"), dated as of September 2, 2020, among the Issuer, Royalty Pharma Holdings Ltd (the "Guarantor") and Wilmington Trust, National Association, as trustee (the "Trustee"), as supplemented by a third supplemental indenture (the "Third Supplemental Indenture" and, together with the Base Indenture, the "Indenture"), dated as of June 10, 2024, among the Issuer, the Guarantor and the Trustee. The Notes are guaranteed on a senior unsecured basis by the Guarantor.

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The 2029 Notes bear interest at a fixed rate of 5.150% per annum, and interest will be payable on March 2 and September 2 of each year, beginning March 2, 2025, until the maturity date of September 2, 2029. The 2034 Notes bear interest at a fixed rate of 5.400% per annum, and interest will be payable on March 2 and September 2 of each year, beginning March 2, 2025, until the maturity date of September 2, 2034. The 2054 Notes bear interest at a fixed rate of 5.900% per annum, and interest will be payable on March 2 and September 2 of each year, beginning March 2, 2025, until the maturity date of September 2, 2054. The Issuer may redeem the Notes at such times and at the redemption prices as provided for in the Indenture. The Indenture also contains certain covenants as set forth in the Indenture and requires the Issuer to offer to repurchase the Notes upon certain change of control events.

The foregoing summary of the Indenture and the Notes does not purport to be complete and is qualified in its entirety by reference to the full text of (i) the Base Indenture attached as Exhibit 4.1 hereto and (ii) the Third Supplemental Indenture attached as Exhibit 4.2 hereto and the form of the Notes included therein, which are incorporated herein by reference.

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%.

On June 10, 2024 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 the completion of enrollment as well as positive initial data from the ongoing Phase 2a trial of SLS009, a highly selective CDK9 inhibitor, in relapsed/refractory acute myeloid leukemia (r/r AML) (Press release, Sellas Life Sciences, JUN 10, 2024, View Source [SID1234644225]).

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"We are pleased to announce the completion of enrollment in the initial portion of our Phase 2a trial representing a significant milestone in the development of SLS009 in AML," said Angelos Stergiou, MD, ScD h.c., President and Chief Executive Officer of SELLAS. "There has been a high level of enthusiasm from the clinical sites, trial investigators, and patients, reflecting the significant unmet need in the AML patient population previously treated with venetoclax-based regimens. We are extremely grateful to everyone who has helped us achieve this important milestone ahead of schedule."

Dr. Stergiou continued: "In addition, we are excited to share very promising initial data from this Phase 2a trial. Efficacy was demonstrated across all cohorts far exceeding the targeted ORR of 20% and median overall survival (mOS) of 3 months. The results also showed that SLS009 was well-tolerated across all doses. These data give us increased confidence in SLS009 as a potential new treatment for AML. We remain committed to advancing the treatment landscape for this underserved patient population and we look forward to continuing the trial, mainly the expansion cohorts, and reporting additional study updates and data in Q3 of this year."

Thirty heavily pretreated patients were recruited in 5 centers across the US, reflecting the high unmet need of this refractory/relapsed patient population. Except for one, all patients in this Phase 2a trial had unfavorable/poor cytogenetic and/or molecular genetics risk (97%) and were treated with continued venetoclax – azacytidine combination therapy after having failed it or similar venetoclax combinations, often more than once. The expected overall survival in those patients is approximately 2.5 months.

Key Highlights from the Initial Data:

Safety:

SLS009 was generally well-tolerated with no safety issues observed across all doses.
There were no dose-limiting and no high-grade treatment-related non-hematologic toxicities. Hematologic toxicities profile was not different from that of venetoclax-based regimens alone.
27 patients had at least one efficacy assessment as of May 25, 2024, and were considered evaluable for efficacy.
Efficacy:

The overall response rate was 29.6% in all evaluable patients, and across all SLS009 doses, with the highest response rate of 50% observed at the dosing regimen of 30 mg BIW.
In the first dose level (safety level, one dose level below recommended Phase 2 dose) of 45 mg once a week (QW), the median overall survival among evaluable patients followed for survival was 5.4 months, compared to the expected survival of 2.5 months in patients refractory to and relapsed on standard venetoclax in combination with hypomethylating agents.
In the second dose level, 60 mg, administered once a week, 3 out of 9 evaluable patients (33%) achieved an overall response defined as leukemia-free status that includes complete response (CR), complete response with incomplete hematologic recovery (CRi), and morphologic leukemia-free state (MLFS). Median survival has not been reached.
In the third dose level of 30 mg twice a week, 4 out of 8 patients (50%) evaluable to date achieved overall response defined as leukemia-free status that includes complete response (CR), complete response with incomplete hematologic recovery (CRi), and morphologic leukemia-free state (MLFS). Median survival has not been reached.
Observed efficacy outcomes exceeded the target ORR of 20% and mOS of 3 months.
The highest response rates were observed among patients harboring ASXL1 mutations as previously reported. Notably, responses were highly correlated with mutational status, with 6 out of 8 responding patients having myelodysplasia-related somatic mutations and 5 having specifically ASXL1 mutations.
A 100% overall response rate (CR/CRi/MLFS) was achieved in patients with ASXL1 mutations in the 30 mg BIW cohort to date.
Based on the preliminary findings from this Phase 2a trial, the trial has been expanded to include two additional cohorts consisting of dosing at 30 mg BIW. One cohort will enroll AML patients with ASXL1 mutations and the other AML patients with myelodysplasia-related molecular mutations other than ASXL1. Study enrollment continues and additional updates and data are expected in Q3.
The Phase 2a clinical trial of SLS009 is an open-label, single-arm, multi-center study designed to evaluate the safety, tolerability, and efficacy of SLS009 in combination with venetoclax and azacitidine at two dose levels, 45 and 60 mg. In the 60 mg dose cohort patients were randomized into either a 60 mg dose once per week or a 30 mg dose two times per week. The target response rate at the optimal dose level is 20% with a target median survival of at least 3 months. In addition, the study aims to identify biomarkers for the target patient population and enrichment for further trials. For more information on the study, visit clinicaltrial.gov identifier NCT04588922.

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.