On November 7, 2023 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) and The University of Texas MD Anderson Cancer Center reported a five-year strategic research collaboration agreement to evaluate zanidatamab, Jazz’s investigational HER2-targeted bispecific antibody, in multiple HER2-expressing cancers (Press release, Jazz Pharmaceuticals, NOV 7, 2023, View Source [SID1234637193]).

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The collaboration will combine MD Anderson’s translational medicine and clinical research expertise with Jazz’s expanding oncology drug development capabilities to investigate the potential of zanidatamab as monotherapy and in combination with other treatments for patients with different tumor types and stages. This includes its possible applicability in early-stage breast cancer, treatment areas where other HER2-directed therapies have failed, cancers with varying degrees of HER2-expression, and potentially rare, tissue-agnostic cancers.

"Current data indicates that zanidatamab has anti-tumor activity in multiple HER2-positive solid tumors, including positive results from a pivotal clinical trial for patients with HER2-amplified biliary tract cancers," said Funda Meric-Bernstam, M.D., chair of Investigational Cancer Therapeutics at MD Anderson. "We are pleased to extend our research efforts with Jazz through this new collaboration, which aims to address significant unmet needs in HER2-expressing solid tumors and to look for safe and effective alternatives to chemotherapy in diseases like early-stage breast cancer."

MD Anderson has been instrumental in researching breakthrough cancer therapies and was a key contributor to early investigations exploring the use of zanidatamab against an actionable target in the treatment of multiple tumor types and the subsequent Phase II HERIZON-BTC-01 trial, which evaluated zanidatamab for patients with treatment-refractory HER2-amplified biliary tract cancers. Results presented at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting demonstrated durable responses and a confirmed objective response rate of 41%. The presentation was selected for the 2023 Best of ASCO (Free ASCO Whitepaper) program.

Jazz and MD Anderson will establish a joint steering committee to oversee the collaboration, which will fund multiple studies over its five-year term. Research under the collaboration is expected to begin in late 2023 or early 2024. This effort builds upon a previous strategic collaboration between Jazz and MD Anderson focused on hematologic malignancies.

"We think zanidatamab has best-in-class potential as a bispecific antibody utilizing biparatopic binding, which results in HER2 signal blockade, as well as immune-mediated cytotoxicity of HER2-expressing cancer cells. Zanidatamab has compelling anti-tumor activity across a broad range of HER2-positive cancers," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development of Jazz Pharmaceuticals. "We look forward to continuing to collaborate with MD Anderson to further evaluate zanidatamab’s potential to be transformative to the current standard-of-care in multiple HER2-expressing cancers. We are dedicated to advancing new treatment options for patients and we believe in the power of collaboration to accelerate the pace of research in difficult-to-treat cancers where persistent treatment gaps remain."

About Zanidatamab
Zanidatamab is an investigational bispecific antibody that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. This unique design results in multiple mechanisms of action including dual HER2 signal blockade, increased binding and removal of HER2 protein from the cell surface, and immune activation leading to encouraging antitumor activity in patients. Zanidatamab is being developed in multiple clinical trials as a targeted treatment option for patients with solid tumors that express HER2. Zanidatamab is being developed by Jazz and BeiGene, Ltd. (BeiGene) under license agreements from Zymeworks, which first developed the molecule.

The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for zanidatamab development in patients with previously treated HER2 gene-amplified biliary tract cancers (BTC), and two Fast Track designations for zanidatamab: one as a single agent for refractory BTC and one in combination with standard of care chemotherapy for first-line gastroesophageal adenocarcinoma (GEA). Additionally, zanidatamab has received Orphan Drug designations from FDA for the treatment of BTC and GEA, as well as Orphan Drug designation from the European Medicines Agency for the treatment of BTC and gastric cancer. Zanidatamab was also granted Breakthrough Therapy designation from the Center for Drug Evaluation (CDE) in China.

On November 7, 2023 Mnemo Therapeutics, a biotechnology company developing transformational immunotherapies, reproted a new preclinical study showing that CAR T cell memory differentiation and persistence can be enhanced by inactivating SUV39H1, an enzyme (histone methyltransferase) that epigenetically regulates and represses memory-associated genes (Press release, Mnemo Therapeutics, NOV 7, 2023, View Source [SID1234637192]). The paper, published in Cancer Discovery, is titled "SUV39H1 Ablation Enhances Long-Term CAR-T Function in Solid Tumors."

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In this preclinical study, researchers at Mnemo and its strategic academic collaborator Institut Curie demonstrated that genetic ablation of histone methyltransferase SUV39H1 reprograms human T cells to express genes associated with memory and stemness (the capability of a cell for self-renewal and differentiation) and to reduce expression of genes associated with T cell exhaustion, which can cause cell therapies to lose their effectiveness over time, resulting in reduced efficacy and tumor relapse. SUV39H1-inactivated CAR T cells promote long-term protection against tumor relapses and rechallenges, demonstrated in mouse models of lung cancer and other solid tumors.

"T cell exhaustion and lack of persistence impede the long-term success of immunotherapy treatments for tumors," said Mnemo Chief Executive Officer Robert LaCaze. "This study shows that inactivating SUV39H1 opens the path to the development of novel therapeutics addressing these challenges with the goal of preventing tumor relapse with immunotherapies."

"This work moves us toward a deeper understanding of the importance of SUV39H1 inactivation in improving T cell persistence and longevity of treatment success," said Sebastian Amigorena, Chief Scientific Officer at Mnemo and senior author on the paper. "Mnemo is grateful to our academic partners, whose collaboration made this rigorous and illuminating study possible. These promising findings are a result of our combined expertise and resources."

On November 7, 2023 The Menarini Group ("Menarini"), a leading international pharmaceutical and diagnostics company, and SciClone Pharmaceuticals (Holdings) Ltd. ("SciClone"), an international biopharmaceutical company, reported that they have entered into an exclusive sub-licensing agreement to develop and commercialize ORSERDU (elacestrant) in the People’s Republic of China (China), in an effort to expand treatment options for appropriate metastatic breast cancer (mBC) patients (Press release, Menarini, NOV 7, 2023, View Source [SID1234637191]).

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ORSERDU, a once-daily oral endocrine monotherapy, for the treatment of postmenopausal women or adult men, with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy, was approved by the U.S. Food and Drug Administration in January 2023 under its priority review and fast track designation. In September 2023, ORSERDU was approved by the European Commission. Stemline Therapeutics, a wholly-owned subsidiary of the Menarini Group, focused on bringing transformational oncology treatments to cancer patients, commercializes ORSERDU in the U.S. and E.U.

Under the Sub-Licensing agreement, SciClone will pursue the development and registration of ORSERDU in China and commercialise ORSERDU upon its regulatory approval in China.

"Patients living with metastatic breast cancer need effective and tolerable options," said Elcin Barker Ergun, CEO of the Menarini Group. "We are proud to partner with SciClone in an effort to register a new breast cancer treatment for patients in China that can offer efficacy in a once-daily pill."

Approximately 70% of breast cancer cases are ER+, HER2-, and up to 40% of ER+, HER2- advanced or mBC tumors harbor ESR1 mutations, which develop as result of exposure to endocrine therapy in the metastatic setting. These mutations are a known driver of resistance to standard endocrine therapy, and until now, the tumors that harbor these mutations have been more difficult to treat.

"China accounts for 20% of breast cancer prevalence worldwide,¹ and we know that these patients need new therapeutic options, particularly in the metastatic setting," said Zhao Hong, Executive Director, President and CEO of SciClone. "We believe that this agreement will enable us to work toward providing oncologists with an important option in the treatment armamentarium for their ER+, HER2- mBC patients whose tumors have an ESR1 mutation."

The approval of ORSERDU in the U.S. and E.U. is supported by data from the Phase 3 EMERALD trial, which demonstrated statistically significant progression-free survival (PFS) with elacestrant versus standard-of-care (SOC), defined as investigator’s choice of an approved endocrine monotherapy. The primary endpoints of the study were PFS in the overall patient population and in patients with ESR1 mutations. In the group of patients whose tumors had ESR1 mutations, elacestrant achieved a median PFS of 3.8 months vs 1.9 months on the SOC, and reduced the risk of progression or death by 45% (PFS HR=0.55, 95% CI: 0.39, 0.77) vs SOC.

A post hoc subgroup analysis of the EMERALD PFS results, which was presented at the San Antonio Breast Cancer Symposium (SABCS) 2022, demonstrated that the duration of prior CDK4/6i treatment was positively associated with longer PFS on elacestrant but not with SOC. For patients with ESR1 mutations who were treated with CDK4/6i for ≥12 months prior to randomization on EMERALD, elacestrant achieved a median PFS of 8.6 months versus 1.9 months on SOC, with a 59% reduction in the risk of progression or death (HR=0.41 95% CI: 0.26-0.63).²

Safety data were consistent with previously reported results. The most common adverse reactions with ORSERDU were musculoskeletal pain, nausea, triglycerides increased, cholesterol increased, vomiting, fatigue, dyspepsia, diarrhea, calcium decreased, back pain, creatinine increased, arthralgia, sodium decreased, constipation, headache, hot flush, abdominal pain, anemia, potassium decreased, and alanine aminotransferase increased. Important Safety Information for ORSERDU is provided below.

About the EMERALD Phase 3 Study (NCT03778931)
The EMERALD Phase 3 trial is a randomized, open label, active-controlled study evaluating elacestrant as second- or third-line monotherapy in ER+, HER2- advanced/metastatic breast cancer patients. The study enrolled 478 patients who had received prior treatment with one or two lines of endocrine therapy, including a CDK4/6 inhibitor. Patients in the study were randomized to receive either elacestrant or the investigator’s choice of an approved hormonal agent. The primary endpoints of the study were progression-free survival (PFS) in the overall patient population and in patients with estrogen receptor 1 gene (ESR1) mutations. In the group of patients whose tumors had ESR1 mutations, elacestrant achieved a median PFS of 3.8 months vs 1.9 months on the SOC, and reduced the risk of progression or death by 45% (PFS HR=0.55, 95% CI: 0.39, 0.77) vs SOC.

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.

Elacestrant is also being investigated in several clinical trials in metastatic breast cancer disease, alone or in combination with other therapies: ELEVATE (NCT05563220); ELECTRA (NCT05386108); and ELCIN (NCT05596409). Elacestrant is also being evaluated in early breast cancer disease.

On November 7, 2023 Tyra Biosciences, Inc. (Nasdaq: TYRA), a clinical-stage biotechnology company focused on developing next-generation precision medicines that target large opportunities in Fibroblast Growth Factor Receptor (FGFR) biology, reported financial results for the quarter ended September 30, 2023 and highlighted recent corporate progress (Press release, Tyra Biosciences, NOV 7, 2023, View Source [SID1234637190]).

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"From the start, TYRA has focused on developing precision therapies that target large opportunities that exist in FGFR biology, and we continue to follow the data. We continue to advance TYRA-300, our oral FGFR3-selective inhibitor, as we dose expand and escalate in our SURF301 oncology study and strengthen our preclinical data package in achondroplasia," said Todd Harris, CEO of TYRA. "Before the end of the year, we expect to update our guidance on the timing and design of our planned Phase 2 study in achondroplasia and the dosing of our first patient with TYRA-200."

Third Quarter 2023 and Recent Corporate Highlights

TYRA-300

SURF301 Phase 1/2 Study for Oncology Continued to Advance. SURF301 (Study in Untreated and Resistant FGFR3+ Advanced Solid Tumors) (NCT05544552) is a multi-center, open label study designed to determine the optimal and maximum tolerated doses (MTD) and the recommended Phase 2 dose of TYRA-300, as well as to evaluate the preliminary antitumor activity of TYRA-300. Enrollment is ongoing in Part A and Part B and dose escalation is ongoing in Part B in Phase 1 of the study at multiple clinical sites in the U.S., Europe, and Australia. In this study, multiple doses and schedules of TYRA-300 will be evaluated to inform dosing decisions in future metastatic urothelial carcinoma (mUC), non-muscle invasive bladder cancer (NMIBC) and achondroplasia studies.

Presented Positive Preclinical Data for Achondroplasia at ASBMR and ASH (Free ASH Whitepaper)G Meetings. In October and early November 2023, TYRA presented additional preclinical results on TYRA-300 in achondroplasia at the American Society for Bone and Mineral Research (ASBMR) and the American Society of Human Genetics (ASHG) 2023 annual meetings, respectively. In preclinical mice models of achondroplasia conducted at The Imagine Institute in Paris, TYRA-300 increased bone growth, improved the shape of the skull, improved the shape of the foramen magnum, restored the architecture of the growth plate, and increased chondrocyte proliferation and differentiation.

Granted Orphan Drug Designation for Achondroplasia from FDA. In July 2023, TYRA-300 was granted Orphan Drug Designation (ODD) for the treatment of achondroplasia from the U.S. Food and Drug Administration (FDA).
TYRA-200

Phase 1 Study on Track to be Initiated by YE ’23. TYRA continued to advance activities to support the initiation of the planned Phase 1 clinical study of TYRA-200, an FGFR1/2/3 inhibitor with potency against activating FGFR2 gene alterations and resistance mutations. The trial will be focused on intrahepatic cholangiocarcinoma resistant to prior FGFR inhibitors. TYRA remains on track to dose the first patient in this trial before year-end 2023.
SNÅP Platform and Pipeline

TYRA continued to advance its in-house precision medicine discovery engine, SNÅP, to develop therapies in targeted oncology and genetically defined conditions including FGF19+/FGFR4-driven cancers and others.
Third Quarter 2023 Financial Results

Third quarter 2023 net loss was $21.2 million compared to $12.5 million for the same period in 2022.
Third quarter 2023 research and development expenses were $19.3 million compared to $10.9 million for the same period in 2022.
Third quarter 2023 general and administrative expenses were $4.7 million compared to $2.7 million for the same period in 2022.
As of September 30, 2023, TYRA had cash and cash equivalents of $215.7 million that are expected to support TYRA’s important clinical and operational milestones over at least the next two years.
About TYRA-300

TYRA-300 is the Company’s lead precision medicine program stemming from its in-house SNÅP platform. TYRA-300 is an investigational, oral, FGFR3-selective inhibitor currently in development for the treatment of cancer and skeletal dysplasias, including achondroplasia. In oncology, TYRA-300 is being evaluated in a multi-center, open label Phase 1/2 clinical study, SURF301 (Study in Untreated and Resistant FGFR3+ Advanced Solid Tumors). SURF301 (NCT05544552) was designed to determine the optimal and MTD and the recommended Phase 2 dose (RP2D) of TYRA-300, as well as to evaluate the preliminary antitumor activity of TYRA-300. SURF301 is currently enrolling adults with advanced urothelial carcinoma and other solid tumors with FGFR3 gene alterations. In skeletal dysplasias, TYRA-300 has demonstrated positive preclinical results, and the Company expects to submit an IND for the initiation of a Phase 2 clinical study in pediatric achondroplasia in 2024. In July 2023, TYRA-300 was granted Orphan Drug Designation for the treatment of achondroplasia from the FDA.

On November 7, 2023 Antengene Corporation Limited ("Antengene" SEHK: 6996.HK), a leading commercial-stage innovative, global biopharmaceutical company dedicated to discovering, developing, and commercializing first-in-class and/or best-in-class medicines for hematology and oncology, reported that it will host its 2023 R&D Day on November 17, 2023, to update the medical and investor communities on the company’s progress with its R&D programs. The session will feature three KOL sessions, and discussions about the data of Antengene’s key drugs in clinical development, including ATG-031 (anti-CD24 monoclonal antibody), ATG-101 (PD-L1/4-1BB bispecific antibody), ATG-022 (Claudin 18.2 antibody-drug conjugate), ATG-037 (CD73 inhibitor), and ATG-008 (dual mTORC1/2 inhibitor); and updates on its proprietary R&D pipeline and upcoming development for 2024 (Press release, Antengene, NOV 7, 2023, View Source [SID1234637189]).

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Three guest experts will participate in the presentations and discussions at the event, they are: Dr. Adnan Khattak, M.D., Ph.D (One Clinical Research, Australia) who will discuss CD73 inhibitors; Dr. Anthony J. Olszanski, M.D., RPh(Fox Chase Cancer Center, the United States) who will discuss tumor immunotherapy, including targeting the PD-L1/4-1BB pathways; and Dr. Shehara Mendis, M.D., M.S. (Cabrini Health, Australia) who will discuss Claudin 18.2-targeting molecules.

Speakers from Antengene’s management team:

Jay Mei, M.D., Ph.D. – Founder, Chairman, and CEO
Amily Zhang, M.D. – Chief Medical Officer
Bo Shan, Ph.D. – Chief Scientific Officer
Godfrey Guo, M.D. – Executive Director, Clinical Development
Bing Hou, Ph.D. – Executive Director, Drug Discovery
A live question and answer session will follow the presentation.

The virtual event will be held in English at 8:30 AM, November 17, 2023, Eastern Time/ 9:30 PM, Beijing Time.

To attend the session, please register at View Source;tp_key=6683586ef4.
For participants in the Mainland of China, please register at View Source;tp_key=6683586ef4
A Hybrid Chinese session will also be held in-person at the Antengene Shanghai Office and virtually at 8:30 AM, November 17, 2023, Beijing Time.

To attend the event virtually, please register at View Source
For in-person attendance, please register at View Source or contact Antengene’s Investor Relations Team at [email protected].