On June 10, 2024 Monopar Therapeutics Inc. (Nasdaq: MNPR), a clinical-stage radiopharmaceutical company focused on developing innovative treatments for cancer patients, reported data from the preclinical development of its novel first-in-class lead radiopharma program MNPR-101-Zr at the 2024 Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting in Toronto, Canada (Press release, Monopar Therapeutics, JUN 10, 2024, View Source [SID1234644223]). SNMMI is the premier educational, scientific, and research event in the radiopharma space. Monopar’s poster presentation can be found at the following link: View Source

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Monopar’s poster highlights the potential promise of both the urokinase plasminogen activator receptor (uPAR) as a radiopharma cancer target for solid tumors as well as MNPR-101 as a targeting agent against uPAR. The data presented demonstrate robust, durable tumor uptake of Zr-89 radiolabeled MNPR-101 (MNPR-101-Zr) in human tumor xenograft mouse models of triple-negative breast, colorectal, and pancreatic cancers. Monopar’s optimization of the MNPR-101-Zr construct achieved markedly higher tumor uptake and drug stability while minimizing accumulation in bone and healthy tissue.

Monopar recently initiated a first-in-human Phase 1 imaging and dosimetry clinical trial in advanced cancer patients with MNPR-101-Zr. The study is led by internationally recognized radiopharmaceutical physician Prof. Rodney Hicks, founder of the Melbourne Theranostic Innovation Centre (MTIC). Further information about the MNPR-101-Zr trial is available at www.ClinicalTrials.gov under study identifier NCT06337084.

On June 10, 2024 Calidi Biotherapeutics, Inc. (NYSE American: CLDI or "Calidi"), a clinical-stage biotechnology company developing a new generation of targeted antitumor virotherapies, reported that it entered into a collaboration agreement with SIGA Technologies (Nasdaq: SIGA) in the first quarter of 2024, to support the development of Calidi’s systemic and targeted RTNova (CLD-400) virotherapy platform, which has the potential to provide a universal treatment for all tumor types (Press release, Calidi Biotherapeutics, JUN 10, 2024, View Source [SID1234644239]). Calidi will initially focus on developing the RTNova platform for lung cancer and metastatic (or advanced stage) solid tumors which account for the majority of cancer deaths.

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The long-term collaboration between Calidi and SIGA aims to harness the capabilities of SIGA’s TPOXX, an antiviral agent effective against vaccinia virus. The initial focus for the collaboration will be on testing the capacity of TPOXX to become a safety switch to manage RTNova’s spread in vivo.

"We believe RTNova is a major breakthrough, and Calidi’s novel systemic targeted virotherapy has the potential to radically shift the treatment landscape for patients across all tumor types," said Antonio F. Santidrian, Chief Scientific Officer of Calidi Biotherapeutics. "By partnering with SIGA, we will have access to a safety switch during the development process, which could provide assurance to patients, physicians, and regulatory bodies during future clinical trials. We are excited about the possibilities this collaboration brings."

RTNova, an enveloped vaccinia virus, is designed to survive in the bloodstream, target multiple tumor sites, and kill tumor cells while altering the tumor immune microenvironment. This novel therapeutic approach not only facilitates easier administration but also broadens the potential patient population who can benefit from this treatment

The U.S. Food and Drug Administration (FDA) approved oral TPOXX in July 2018 for the treatment of smallpox to mitigate the impact of a potential outbreak or bioterror attack. Preclinical studies have demonstrated TPOXX’s efficacy against all orthopoxviruses that have been tested, including vaccinia (published in The New England Journal of Medicine, July 2018). The unique mechanism of action of TPOXX coupled with published efficacy in animal studies make it an important addition to the development of vaccinia-based cancer therapies.

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%.