On January 12, 2024 Sermonix Pharmaceuticals Inc., a privately held biopharmaceutical company developing innovative therapeutics to specifically treat metastatic breast cancers harboring ESR1 mutations, and Shanghai Henlius Biotech, Inc. (2696.HK), reported a strategic collaboration agreement in which Henlius will receive exclusive rights to develop, manufacture and commercialize Sermonix’s lead investigational drug, lasofoxifene, in China (Press release, Sermonix Pharmaceuticals, JAN 10, 2024, View Source [SID1234639216]).

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Under the terms of the agreement, Henlius will receive exclusive rights and sublicenses to lasofoxifene for at least two estrogen receptor-positive (ER+)/HER2- breast cancer indications in the territory, with Sermonix retaining all other global rights. Sermonix received an upfront payment and is further eligible to receive up to $58 million in certain predetermined milestones, in addition to royalties upon Henlius commercialization in China.

"In Phase 2 clinical trials, investigational lasofoxifene demonstrated its potential for the treatment of ER+/HER2- breast cancer harboring ESR1 mutation," said Ping Cao, senior vice president and chief business development officer of Henlius. "Lasofoxifene will play a critical role in complementing Henlius’ pipeline of its breast cancer product. In collaboration with Sermonix, we look forward to accelerating the access of more effective, personalized, precise and well-tolerated treatment solutions for Chinese patients."

"With a strong platform of R&D resources and commercialization capabilities, Henlius is an ideal partner to bring lasofoxifene into the therapeutic landscape in China," said Dr. David Portman, Sermonix founder and chief executive officer. "Previous studies demonstrated lasofoxifene’s best-in-class potential and we will work with Henlius to accelerate the clinical development of the Phase 3 ELAINE-3 multi-regional clinical trial in China, making lasofoxifene available to Chinese patients as soon as possible."

Breast cancer is the cancer with the highest incidence rate in the world, according to GLOBOCAN 2020. There were 2.26 million new cases of breast cancer in 2020 globally, including more than 410,000 in China [1]. ER+ breast cancer comprises 60-70% of all breast cancers [2]. Endocrine therapy remains the mainstay treatment for ER+ breast cancer and the most widely used class of aromatase inhibitor (AI) has been recommended by the National Comprehensive Cancer Network (NCCN) and Chinese Society of Clinical Oncology (CSCO) guidelines to be the adjuvant and first-line standard of care for patients with ER+/HER2- breast cancer [3-4]. However, almost all patients treated with AIs develop primary or acquired resistance [5], with acquired mutations in the estrogen receptor α gene (ESR1) being the most prevalent (up to 40%). This is a significant mechanism of resistance to endocrine therapy [6]. Currently, there are limited treatment options for ER+/HER2- breast cancer with ESR1 mutations, and thus a large clinical need exists.

The Phase 3 ELAINE-3 multi-regional clinical trial (NCT05696626) is the third of Sermonix’s Evaluation of Lasofoxifene in ESR1 Mutations (ELAINE) studies. With the Phase 2 ELAINE-1 and ELAINE-2 studies both completed and having shown compelling anti-tumor activity against tumors with increasingly prevalent ESR1 mutations [7-8], Sermonix in December 2023 activated and began enrollment for ELAINE-3 in the U.S.

ELAINE-3 will assess the efficacy of lasofoxifene and Eli Lilly and Company’s (NYSE:lly) 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.

Henlius will fund the clinical development and patient enrollment of the ELAINE-3 study in China, and be responsible for regulatory approval and post-marketing manufacturing and commercialization in the region.

About Lasofoxifene
Lasofoxifene is an investigational novel endocrine therapy in clinical development which has demonstrated robust target engagement as an ESR1 antagonist in the breast, particularly in the presence of ESR1 mutations. Lasofoxifene has demonstrated anti-tumor activity as monotherapy and in combination with a CDK4/6 inhibitor in Phase 2 studies and has unique tissue selectivity distinguishing it from other current and investigational endocrine therapies, with beneficial effects seen on vagina and bone in previous clinical studies. Lasofoxifene, which Sermonix licensed globally from Ligand Pharmaceuticals Inc. (NASDAQ:LGND), has been studied in previous comprehensive Phase 1-3 non-oncology clinical trials in more than 15,000 postmenopausal women worldwide. Lasofoxifene’s bioavailability and activity in mutations of the estrogen receptor could potentially hold promise for patients who have acquired endocrine resistance due to ESR1 mutations, a common finding in the metastatic setting and an area of high unmet medical need. Lasofoxifene’s novel activity in ESR1 mutations was discovered at Duke University and Sermonix has exclusive rights to develop and commercialize the product in this area. Lasofoxifene, a novel targeted and tissue selective oral endocrine therapy, could, if approved, play a critical role in the precision medicine treatment of advanced ER+ breast cancer.

On January 11, 2024 iTeos therapeutics presented its corporate presentation (Presentation, iTeos Therapeutics, JAN 10, 2024, View Source [SID1234639206]).

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On January 10, 2024 Focal Medical, Inc., ("Focal") a privately held biopharmaceutical company developing a targeted therapeutic system to treat inoperable tumors and to deliver genomic medicines, reported U.S. Food and Drug Administration (FDA) clearance of an Investigational New Drug (IND) application to initiate a Phase 1b clinical trial of ACT-IOP-003, the Company’s first targeted therapeutic product (Press release, Focal Medical, JAN 10, 2024, View Source [SID1234639197]). The trial will evaluate the safety and tolerability of targeted delivery of gemcitabine to locally advanced nonresectable (LANR) pancreatic tumors. The clinical trial is expected to start mid-2024.

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"Pancreatic cancer is a devastating disease with a very poor prognosis," said Dr. William Daunch, Chief Technology Officer of Focal. "Once a locally advanced tumor is not resectable, treatment options are limited and these patients experience a significantly reduced survival outlook compared to resectable cases. Our thesis, which we have demonstrated in animal models of pancreatic cancer, is that localized delivery of high concentrations of gemcitabine via our implantable iontophoretic device can reduce tumor volume to a point where surgical removal may be possible, while also minimizing systemic exposure and associated toxicity. If successful, we may offer the opportunity of extended survival for the significant number of pancreatic cancer patients presenting with nonresectable disease."

Pancreatic adenocarcinoma, which represents more than 90 percent of pancreatic cancer diagnoses, is an especially challenging disease to treat. According to The American Cancer Society, the incidence of pancreatic cancer in the U.S. is more than 62,000 cases annually and it represents the third leading cause of cancer death. Patients whose tumors are resectable have the best chance for cure and, for these patients, surgical resection with or without neoadjuvant chemotherapy, is the standard of care. Treatment options for locally advanced nonresectable tumors comprise a variety of systemic chemotherapy regimens, which are rarely curative unless there is dramatic response to chemotherapy that allows the tumor to be resected.

The multi-center, open label, modified dose escalation phase 1b clinical trial will assess the safety, tolerability, and clinical activity of the implantable ACT-IOP-003 targeted therapeutic product delivering gemcitabine directly into the pancreas to treat LANR pancreatic cancer. Eligible patients would be enrolled into one of two cohorts, receiving treatment either once or twice weekly over 8 weeks (approximately 5 patients per cohort). Up to 12 patients may be enrolled in the study which is expected to start mid-2024.

"Clinicians who treat pancreatic cancer need new and more powerful tools in their armamentarium to address this terrible disease," commented Jen Jen Yeh, M.D., Focal Medical Co-founder and Non-executive Director, and Professor and Vice Chair of Research, Department of Surgery and Director of the Pancreatic Cancer Center of Excellence at the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill. "The novel approach that the Focal Medical system employs to drive gemcitabine directly and selectively into the pancreas may offer new hope for patients."

Michael Aldridge, CEO of Focal added, "The FDA’s clearance of Focal’s IND for ACT-IOP-003 for pancreatic cancer is an important achievement for the Company. We remain focused on our important mission to provide hope for patients suffering with this devastating disease."

On January 10, 2024 Novocure (NASDAQ: NVCR) reported that the final patient has been enrolled in the global phase 3 TRIDENT clinical trial evaluating the safety and efficacy of initiating Optune Gio (formerly known as Optune) concurrent with radiation therapy and temozolomide (TMZ) for the treatment of adult patients with newly diagnosed glioblastoma (GBM) (Press release, NovoCure, JAN 10, 2024, View Source [SID1234639196]).

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"TTFields therapy has played a critical role in the treatment of newly diagnosed glioblastoma for nearly a decade, and the TRIDENT trial represents the potential evolution of this treatment paradigm by introducing TTFields earlier, at the same time as radiation therapy and temozolomide," said Asaf Danziger, Novocure’s Chief Executive Officer. "Preclinical research has shown that the application of TTFields together with radiation therapy leads to a more pronounced cytotoxic effect in glioma cell lines as compared to TTFields after administration of radiation therapy. The TRIDENT study could unlock our ability to reach patients earlier in their treatment journey, further extending patient survival. We remain committed to exploring opportunities to further extend the survival horizon for patients diagnosed with glioblastoma."

Optune Gio is currently approved for use together with maintenance TMZ for the treatment of newly diagnosed GBM following maximal debulking surgery and the completion of radiation therapy.

The TRIDENT clinical trial is a randomized, open-label study designed to enroll 950 adult patients with newly diagnosed GBM. Following maximal debulking surgery, patients enrolled in TRIDENT were randomized to receive either TTFields therapy, concomitant with TMZ and radiation therapy, or TMZ and radiation therapy for six weeks. Following the initial six-week period, all patients receive the current standard of care – TTFields therapy together with maintenance TMZ for a period of 24 months or until a second disease progression is experienced. TRIDENT began enrolling patients in December 2020 and is the largest trial Novocure has conducted to date.

Final data from the TRIDENT trial is anticipated in 2026. The trial’s primary endpoint is overall survival. Secondary endpoints are progression-free survival, one-year and two-year survival rate, overall radiological response, next progression-free survival, progression-free survival at six and 12 months, severity and frequency of adverse events, pathological changes in resected GBM tumors following study treatments, quality of life, dependence of overall survival on TTFields dose at the tumor, and neurological assessment using the NANO scale.

About Optune Gio

Optune Gio delivers Tumor Treating Fields (TTFields) therapy to the region of the tumor. Optune Gio, previously known as Optune, is a noninvasive, antimitotic cancer treatment for glioblastoma (GBM).

TTFields therapy uses electric fields to physically disrupt cell division. TTFields therapy does not stimulate or heat tissue and targets dividing cancer cells of a specific size. TTFields therapy takes advantage of the special characteristics and geometrical shape of dividing cells, which make them susceptible to the effects of the alternating electric fields. TTFields therapy causes minimal damage to healthy cells. Mild to moderate skin irritation is the most common side effect reported. TTFields therapy is approved in certain countries for the treatment of adults with glioblastoma, malignant pleural mesothelioma and pleural mesothelioma, some of the most difficult cancer types to treat.

Important Safety Information

Contraindications

Do not use Optune Gio in patients with an active implanted medical device, a skull defect (such as, missing bone with no replacement), or bullet fragments. Use of Optune Gio together with implanted electronic devices has not been tested and may theoretically lead to malfunctioning of the implanted device. Use of Optune Gio together with skull defects or bullet fragments has not been tested and may possibly lead to tissue damage or render Optune Gio ineffective.

Do not use Optune Gio in patients that are known to be sensitive to conductive hydrogels. In this case, skin contact with the gel used with Optune Gio may commonly cause increased redness and itching, and rarely may even lead to severe allergic reactions such as shock and respiratory failure.

Warnings and Precautions

Do not prescribe Optune Gio for patients that are pregnant, you think might be pregnant or are trying to get pregnant, as the safety and effectiveness of Optune Gio in these populations have not been established.

The most common (≥10%) adverse events involving Optune Gio in combination with temozolomide were thrombocytopenia, nausea, constipation, vomiting, fatigue, medical device site reaction, headache, convulsions, and depression.

The most common (≥10%) adverse events seen with Optune Gio monotherapy were medical device site reaction and headache.

The following adverse reactions were considered related to Optune Gio when used as monotherapy: medical device site reaction, headache, malaise, muscle twitching, fall and skin ulcer.

Use of Optune Gio in patients with an inactive implanted medical device in the brain has not been studied for safety and effectiveness, and use of Optune Gio in these patients could lead to tissue damage or lower the chance of Optune Gio being effective.

If the patient has an underlying serious skin condition on the scalp, evaluate whether this may prevent or temporarily interfere with Optune Gio treatment.

On January 10, 2024 Dxcover Limited, a clinical-stage diagnostics company pioneering multi-omic spectral analysis (MOSA) for early detection of multiple cancers, reported that it is initiating three pivotal clinical trials measuring efficacy of the company’s liquid biopsy technology for the detection of brain, colorectal and lung cancer (Press release, Dxcover, JAN 10, 2024, View Source [SID1234639195]).

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The company has launched its EMBRACE study, a 2,200-patient trial focused on the early detection of brain cancer. Dxcover Brain Cancer is a qualitative in vitro diagnostic (IVD) test analyzing blood serum by infrared spectroscopy to detect the signals indicative of brain cancer. This highly sensitive test is to help determine the necessary treatment of patients presenting vague symptoms in primary care environments. The results of the test would prioritize individuals who require a confirmatory brain scan, potentially enabling earlier detection to save lives and reduce healthcare costs. The Dxcover Brain Cancer test has been developed over four years with clinical support from NHS Lothian. This pivotal study is partially funded by a €2.5m grant from the European Innovation Council.

The CREATE2 trial will be conducted to evaluate diagnostic accuracy for colorectal cancer and high-risk adenoma in patients undergoing a colonoscopy. The study will have two recruitment pathways, one in the US and one in the UK, each with 700 patients. The US cohort will be assessed in the average risk population 45-84 who are intending to undergo a screening colonoscopy, while the UK cohort will be assessed post-referral at colonoscopy. CREATE2 aims to validate the previous CREATE study which showed Dxcover’s ability to achieve accurate detection of pre-cancerous lesions and stage 1 colorectal cancer, detection at these stages will enable a positive impact on patients’ lives.

The SPIRALS trial is focused on the management of indeterminant pulmonary nodules by scanning for nodules in the size range between 0.8 – 3.0 mm range. At this size range the nodules are small, however 80% have an intermediate risk score where next steps are unclear resulting in unnecessary surgery and missed cancer diagnoses. Dxcover will be analyzing more than 1,800 samples in order to provide a rapid, cost-effective tool that can help patients receive the correct next steps in their journey.

"Each cancer follows a unique development path, and these are important trials to assess brain, colorectal and lung cancer separately to zero in on the distinct triggers of each disease and, based on the results, identify the most effective treatment for each patient," said Professor Matthew Baker, Founder and CEO, Dxcover. "As the medical community gathers this week in San Francisco for what is always one of the most significant gatherings in the healthcare industry, I’m looking forward to meeting with like-minded partners whose mission is to eradicate the devastating effects of cancers. At Dxcover, we are firm believers that the key to improving patient outcomes lies in the early detection of cancer, expanding intervention and treatment options. Not only does this have the potential to enhance the efficacy of medical intervention, but also contributes to prolonging and promoting healthier lives."

The Dxcover Cancer Liquid Biopsy test uses Fourier transform infrared (FTIR) spectroscopy and machine learning algorithms to build a classifier of the resultant spectral profiles to detect cancer and can be fine-tuned to maximize either sensitivity or specificity depending on the requirements of specific disease pathway.