On December 12, 2024 The Menarini Group ("Menarini"), a leading international pharmaceutical and diagnostics company, and Stemline Therapeutics, Inc. ("Stemline"), a wholly-owned subsidiary of the Menarini Group focused on bringing transformational oncology treatments to cancer patients, along with MEDSIR, a leading global independent clinical research company in oncology and part of Oncoclínicas & Co., the largest specialized oncology treatment group in Latin America, reported research on the pioneering clinical trial ADELA (Press release, Menarini, DEC 12, 2024, View Source [SID1234649089]). This important research addresses therapeutic resistance in advanced ER+/HER2- breast cancer. Presented at the San Antonio Breast Cancer Symposium 2024 (SABCS), the study represents a key milestone in the quest for more effective and personalized treatment options for patients with disease progression.

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The standard first-line treatment for advanced ER+/HER2- breast cancer combines endocrine therapy with CDK4/6 inhibitors. ESR1 mutations develop as a result of prior exposure to endocrine therapy during metastatic treatment, and up to 50% of ER+, HER2- advanced or metastatic breast cancers will develop these mutations. ESR1 mutations cause the tumors to become resistant to endocrine therapy, in turn causing the cancer to progress; therefore, it is important to test for ESR1 whenever mBC progresses. Longer exposure to endocrine therapy during first-line treatment increases the chance of a patient’s tumor developing an ESR1 mutation. With the goal of addressing this unmet medical need, the ADELA phase III clinical trial investigates a new therapeutic option combining elacestrant, a next generation, oral selective estrogen receptor degrader, with everolimus, an mTORC1 inhibitor.

This combination is being evaluated in patients with advanced ER+/HER2- breast cancer that harbors ESR1 mutations, and who have experienced progression after standard first-line treatment. Results from the phase III EMERALD study were the basis for elacestrant’s approval. Meanwhile, everolimus has shown efficacy in inhibiting other resistance mechanisms in this type of cancer. The elacestrant and everolimus combination has demonstrated preliminary efficacy with a manageable safety profile in the phase 1b/2 ELEVATE study (NCT05563220).

"We at Menarini Stemline are delighted to announce the collaboration with MEDSIR to continue advancing the clinical research to explore the combination therapy with elacestrant," said Nassir Habboubi, MD, Chief Medical Officer of Stemline Therapeutics. "We are committed to driving innovation in cancer treatment by delivering transformational therapies aiming to extend the lives of people living with cancer."

The primary objective of this international, randomized, double-blind trial is to evaluate whether the combination of elacestrant and everolimus offers greater efficacy in delaying disease progression compared to elacestrant monotherapy. Additionally, it investigates other crucial aspects, such as overall survival, toxicity profile, and the impact on patients’ quality of life.

The ADELA study represents a critical step in understanding how to overcome tumor resistance challenges in patients with ESR1 mutations, with the goal of advancing towards more effective and safer treatments.

"At MEDSIR, we understand innovation not only as achieving clinical results but as the ability to transform patients’ lives on a global scale. With ADELA, we take a decisive step toward accomplishing less invasive and more accessible treatments, aiming to offer new hope to those facing the most complex forms of the disease. This advancement reinforces our commitment to increasingly personalized and patient-centered medicine, a fundamental pillar in shaping the future of oncology," said Dr. Antonio Llombart-Cussac, Senior Scientific Leader at MEDSIR.

The phase III study not only has significant clinical objectives, but also holds the potential to pave the way for regulatory approval of this therapeutic combination, enabling its use in a broader population of patients with advanced breast cancer. Moreover, the international scope of the study, which includes participation from multiple countries, including Spain, Italy, France, Austria, the Czech Republic, Greece, Germany, and the United Kingdom, underscores the study’s global importance and relevance in the scientific community.

The presentation of the ADELA study at an event as prominent as SABCS 2024 reinforces MEDSIR’s leadership in excellence-driven oncology research and highlights its focus on addressing unmet needs in breast cancer treatment. The ADELA study is active and already recruiting patients.

About ORSERDU (elacestrant)

U.S. Indication: ORSERDU (elacestrant), 345 mg tablets, is indicated for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy.

Full prescribing information for the U.S. can be found at www.orserdu.com.

Important Safety Information
Warning and Precautions

Dyslipidemia: Hypercholesterolemia and hypertriglyceridemia occurred in patients taking ORSERDU at an incidence of 30% and 27%, respectively. The incidence of Grade 3 and 4 hypercholesterolemia and hypertriglyceridemia were 0.9% and 2.2%, respectively. Monitor lipid profile prior to starting and periodically while taking ORSERDU.

Embryo-Fetal Toxicity: Based on findings in animals and its mechanism of action, ORSERDU can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with ORSERDU and for 1 week after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ORSERDU and for 1 week after the final dose.

Adverse Reactions

Serious adverse reactions occurred in 12% of patients who received ORSERDU. Serious adverse reactions in >1% of patients who received ORSERDU were musculoskeletal pain (1.7%) and nausea (1.3%). Fatal adverse reactions occurred in 1.7% of patients who received ORSERDU, including cardiac arrest, septic shock, diverticulitis, and unknown cause (one patient each).
The most common adverse reactions (≥10%), including laboratory abnormalities, of ORSERDU were musculoskeletal pain (41%), nausea (35%), increased cholesterol (30%), increased AST (29%), increased triglycerides (27%), fatigue (26%), decreased hemoglobin (26%), vomiting (19%), increased ALT (17%), decreased sodium (16%), increased creatinine (16%), decreased appetite(15%), diarrhea(13%), headache (12%), constipation (12%), abdominal pain (11%), hot flush (11%), and dyspepsia (10%).

Drug interactions

Concomitant use with CYP3A4 Inducers and/or inhibitors: Avoid concomitant use of strong or moderate CYP3A4 inhibitors with ORSERDU. Avoid concomitant use of strong or moderate CYP3A4 inducers with ORSERDU.

Use in specific populations

Lactation: Advise lactating women to not breastfeed during treatment with ORSERDU and for 1 week after the last dose.
Hepatic Impairment: Avoid use of ORSERDU in patients with severe hepatic impairment (Child-Pugh C). Reduce the dose of ORSERDU in patients with moderate hepatic impairment (Child-Pugh B).
The safety and effectiveness of ORSERDU in pediatric patients have not been established.

To report SUSPECTED ADVERSE REACTIONS, contact Stemline Therapeutics, Inc. at 1-877-332-7961 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

On December 12, 2024 Immuneering Corporation (Nasdaq: IMRX), a clinical-stage oncology company seeking to develop and commercialize universal-RAS/RAF medicines for broad populations of cancer patients, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for its lead clinical-stage program, IMM-1-104, as a treatment for patients with unresectable or metastatic NRAS-mutant melanoma who have progressed on or are intolerant to PD-1/PD-L1 based immune checkpoint inhibitors (Press release, Immuneering, DEC 12, 2024, View Source [SID1234649074]). IMM-1-104 is currently being evaluated in a Phase 2a clinical trial in patients with advanced solid tumors, including melanoma.

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"Immune checkpoint inhibitors play a vital role in the treatment of melanoma, yet patients who progress on or are intolerant to them have limited options," said Ben Zeskind, Ph.D., Co-Founder and CEO of Immuneering. "Targeted therapies including MEK and RAF inhibitors have shown promise in melanoma but historically are severely limited by toxicity. As we presented at the European Society for Medical Oncology 2024 congress, IMM-1-104 is a new kind of MEK inhibitor that was observed to be uniquely well tolerated in our Phase 1 trial, relative to MEK inhibitors currently used to treat melanoma. We believe this creates opportunities for IMM-1-104 to benefit melanoma patients both alone and in combination with RAF inhibitors and/or immune checkpoint inhibitors. Against this backdrop, we are pleased with the FDA’s decision to grant Fast Track designation for IMM-1-104 in advanced melanoma, an area of significant unmet need. Melanoma patients are actively enrolling in one of the five arms of our Phase 2a clinical trial, and this designation follows our announcements earlier this year that IMM-1-104 has also been granted Fast Track designations for the treatment of both first and second-line pancreatic cancer."

Fast Track designation is a program designed to facilitate the development and expedite the review of medicines with the potential to treat serious conditions and fulfill an unmet medical need. An investigational medicine that receives Fast Track designation may be eligible for more frequent interactions with the FDA to discuss the candidate’s development plan and, if relevant criteria are met, may be eligible for accelerated approval and priority review.

About IMM-1-104

IMM-1-104 aims to achieve universal-RAS activity that selectively impacts cancer cells to a greater extent than healthy cells, through Deep Cyclic Inhibition of the MAPK pathway with once-daily dosing. IMM-1-104 is currently being evaluated in a Phase 1/2a study in patients with advanced solid tumors harboring RAS mutations (NCT05585320).

On December 12, 2024 Laekna (2105.HK) reported that the company will present an internally discovered preclinical candidate at the 2024 San Antonio Breast Cancer Symposium (SABCS) on December 13, 2024 (Press release, Laekna Therapeutics, DEC 12, 2024, View Source [SID1234649090]). The presentation will feature preclinical characterization of LAE118, a novel allosteric pan-mutant selective PI3Kα inhibitor.

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"We appreciate this recognition of our expertise and strength in pre-clinical developments of novel drugs", said Dr. Justin Gu, Chief Scientific Officer of Laekna. "The development of LAE118 was led by Dr. Ming Li, with collaborative contributions from the Med Chem, Biology and AIDD (AI-driven Drug Discovery) teams of Laekna. We have significantly accelerated the development of our preclinical drug candidate with cutting-edge artificial intelligence tools".

"As a novel allosteric inhibitor, LAE118 demonstrates excellent potency and selectivity towards various PI3Kα mutants. With superior efficacy and higher tolerability than its competitors in animal models, LAE118 has great potential to become the best-in-class pan-mutant-selective PI3Kα inhibitor. We look forward to bringing this novel therapy to the patients", said Dr. Justin Gu.

PI3Kα mutations are prevalent in patients with breast, colorectal, lung, endometrial, and numerous other cancers. Targeting PI3Kα in cancer has been validated as a therapeutic strategy, as evidenced by the approved drugs. However, the first-generation drugs inhibit the wild-type PI3Kα with equal potency, which raises concerns of tolerability and therapeutic efficacy. Therefore, there is a pressing need to develop novel PI3Kα-targeted therapies that can minimize on-target toxicities and overcome drug resistance.

While making significant progress in pre-clinical developments of drug candidates in cancer, Laekna has also established a comprehensive Activin-ActRII portfolio in metabolism. Following the clinical collaboration with Eli Lilly on LAE102 (ActRIIA selective antibody), Laekna has progressedLAE103, an ActRIIB selective inhibitor and LAE123, a dual inhibitor against ActRIIA/IIB, into IND-enabling studies, aiming to advance them to the clinical stage swiftly.

The San Antonio Breast Cancer Symposium is an annual event cosponsored by the AACR (Free AACR Whitepaper) and UT Health San Antonio’s Mays Cancer Center. The meeting is the largest and most prestigious scientific gathering on breast cancer research.

Presentation details are as follows:

Abstract Number: SESS-3548

Poster Number: P5-06-16

Title: Preclinical characterization of LAE118, a novel allosteric pan-mutant selective PI3Kα inhibitor

Authors: Ming Li, Ruipeng Zhang, Junyan Chen, Meijuan Hu, Xiaofen Lin, Minhua Zhang, Xiang-Ju Justin Gu

Time: Friday, Dec. 13, 2024, 12:30 p.m. – 14:00 p.m. CST

Location: Halls 2-3, Henry B. Gonzalez Convention Center, San Antonio, Texas

Abstract Highlights:

LAE118 is a novel allosteric pan-mutant selective PI3Kα inhibitor. LAE118 demonstrates excellent in vitro anti-proliferation activities in PI3Kα mutant cell lines and remains active against cells resistant to orthosteric PI3Kα inhibitors. LAE118 shows strong anti-tumor growth effect in Xenograft models at a dose that is much lower than other allosteric inhibitors and has less effect on glucose homeostasis compared to orthosteric PI3Kα inhibitors. In pre-clinical toxicology studies, LAE118 also demonstrated good tolerability. These data indicate that LAE118 offers improved efficacy and larger safety window. LAE118 is currently in IND enabling stage and Laekna aims to submit the IND application at the earliest opportunity.

On December 12, 2024 INOVIO Pharmaceuticals, Inc. (Nasdaq: INO), a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases, reported that it intends to offer and sell shares of its common stock and accompanying warrants to purchase shares of its common stock, in an underwritten public offering (Press release, Inovio, DEC 12, 2024, View Source [SID1234649075]). All of the securities in the proposed offering will be sold by INOVIO. The proposed offering is subject to market conditions, and there can be no assurance as to whether or when the offering may be completed, or the actual size or terms of the offering.

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Oppenheimer & Co. Inc. and Citizens JMP are acting as joint book-running managers for the offering. Stephens Inc. is acting as lead manager for the offering.

A shelf registration statement relating to the shares of common stock and accompanying warrants offered in the offering described above was filed with the Securities and Exchange Commission (SEC) on November 9, 2023 and declared effective by the SEC on January 31, 2024. The offering will be made only by means of a written prospectus and prospectus supplement that form a part of the registration statement. A preliminary prospectus supplement and accompanying prospectus relating to and describing the terms of the proposed offering will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. Copies of the preliminary prospectus supplement and the accompanying prospectus, when available, may also be obtained by contacting: Oppenheimer & Co. Inc., Attention: Syndicate Prospectus Department, 85 Broad Street, 26th Floor, New York, NY 10004, by telephone at (212) 667-8055, or by email at [email protected]; or Citizens JMP Securities, LLC, 600 Montgomery Street, Suite 1100, San Francisco, California 94111, by telephone at (415) 835-8985, or by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy the securities being offered, nor shall there be any sale of the securities being offered in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

On December 12, 2024 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global oncology company that intends to change its name to BeOne Medicines Ltd., reported it has entered into a global licensing agreement with CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd. ("CSPC") for SYH2039, a novel methionine adenosyltransferase 2A (MAT2A)-inhibitor being explored for solid tumors (Press release, BeiGene, DEC 12, 2024, View Source [SID1234649091]).

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SYH2039 targets solid tumors that have a mutation called MTAP deletion, which is estimated to be present in approximately 15 percent of all cancer types with the most common including glioblastoma, pancreatic cancer and non-small cell lung cancer.

"With one of the most dynamic solid tumor portfolios in the industry, we are continually assessing opportunities that align with our strategic focus and address significant unmet needs for patients. This MAT2A inhibitor is a valuable addition to our solid tumor pipeline, and we’re eager to explore its potential, particularly in combination with our internally developed PRMT5 inhibitor, BGB-58067. Together, these assets hold promise for advancing treatment across a range of solid tumors," said Lai Wang, Ph.D., Global Head of R&D at BeiGene.

BGB-58067, which is on track to enter the clinic before the end of the year, is designed to avoid on-target hematological toxicity seen with first-generation PRMT5 inhibitors. It has best-in-class potential with high potency, selectivity, and brain penetrability.

Under the terms of the agreement, BeiGene has an exclusive license to develop, manufacture and commercialize SYH2039 worldwide. CSPC will receive upfront and time-based payments totaling $150 million and will be eligible for payments upon the achievement of certain development and commercial milestones and tiered royalties.

BeiGene is focused on growing its leadership in solid tumors with its PD-1 inhibitor TEVIMBRA (tislelizumab) and by advancing potential best-in-class assets for lung, breast and gastrointestinal cancers, including several differentiated antibody drug conjugates, multi-specific antibodies, targeted protein degraders, and small molecule inhibitors. The Company recently announced its intent to change its name to BeOne, reaffirming its commitment to develop innovative medicines to eliminate cancer by partnering with the global community to serve as many patients as possible.