On December 4, 2024 TC BioPharm (Holdings) PLC ("TC BioPharm" or the "Company") (NASDAQ: TCBP) a clinical-stage biotechnology company developing platform allogeneic gamma-delta T cell therapies for cancer and other indications, reported an update on the progression of the ACHIEVE UK Trial (Press release, TC Biopharm, DEC 4, 2024, View Source [SID1234648810]).

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As of this week, over half of the Cohort A patients in Stage One of the ACHIEVE study have received TCB008. These patients have an unmet clinical need, as they have been unable to attain remission with the existing Standard of Care, other treatments, or tolerate further chemotherapy. Data evaluated at this milestone demonstrate positive safety signals for the 5mL dose of TCB008, as no Serious Adverse Events have been attributed to the TCB008 drug product. The Company intends to use this data to justify further increases in the TCB008 dose, from 230 million Gamma Delta T-Cells up to 819 million Gamma Delta T-Cells, to identify the optimal dose for Cohort A patients.

Cohort B patients with residual disease after initially achieving remission with existing available treatment continue to be actively recruited into the ACHIEVE study at the current TCB008 dose of 230 million Gamma Delta T-Cells. These patients will be recruited at 1 of the 4 active clinical trial sites. Each site, including Guy’s and St. Thomas, is led by a Principal Investigator, who are experienced hematologists who oversee the use of TCB008 as an experimental acute myeloid leukemia treatment. Two more sites will be onboarded in the first half of 2025 for 6 recruiting sites in the United Kingdom.

"Medicinal products cannot be effective if they are not safe, and it’s clear from these initial data that TCB008 is safe for our patients," said Alison Bracchi, Executive Vice President of Clinical Operations. "Our priority now, for Cohort A, is to find the optimal biologically effective dose for patients that have exhausted all other treatments to drive a long term response. We look forward to completing the recruitment of Cohort B patients, and are planning to evaluate these data in the first half of 2025."

The increased TCB008 dose will be implemented concurrently to the scaled-up manufacturing process, developed by Dr. Lauren Bor’s team, in 2025.

"The operational teams at TC BioPharm are incredibly resourceful," said Callum Fiske, Head of Operations. "Cross-functional collaboration is ongoing to deliver improvements to the manufacturing process as soon as possible, enabling increased yields that will expedite TCB008 delivery from cleanroom to clinic, and drive economic efficiencies to the commercial cost, in 2025."

On December 4, 2024 Physician-scientists from Rutgers Cancer Institute and RWJBarnabas Health reported that it will showcase a diverse range of hematology/oncology data from their clinical research program at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, being held in San Diego, California (and online) from December 7-10, 2024 (Press release, Rutgers Cancer Institute of New Jersey, DEC 4, 2024, View Source [SID1234648809]). A total of 66 abstracts have been accepted (including 21 oral presentations, 39 poster presentations, 1 special-interest session, 1 oral symposium, 2 satellite symposia and 2 scientific workshops), comprising of clinical data and analyses that advance the understanding, treatment, and prognosis of blood cancers and disorders such as sickle cell disease, lymphoma, leukemia, and myeloma. Rutgers Cancer Institute, together with RWJBarnabas Health, is New Jersey’s only National Cancer Institute-designated Comprehensive Cancer Center.

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Rutgers Cancer Institute and RWJBarnabas Health (PRNewsfoto/Rutgers Cancer Institute and RWJBarnabas Health)
Rutgers Cancer Institute and RWJBarnabas Health (PRNewsfoto/Rutgers Cancer Institute and RWJBarnabas Health)
"At the heart of our research efforts is a commitment to improving patients’ lives and serving our community. This promise is shared by our nationally recognized team of cancer specialists, who work tirelessly to translate groundbreaking discoveries into the best options for our patients," said Matthew Matasar, MD, Chief, Division of Blood Disorders, Rutgers Cancer Institute, and Professor of Medicine, Rutgers Robert Wood Johnson Medical School. "The impressive contributions of our faculty, showcased at this year’s ASH (Free ASH Whitepaper) Annual Meeting, underscore the clinical excellence, innovation, and discovery that define Rutgers Cancer Institute and RWJBarnabas Health. We’re proud to lead cutting-edge research that has the potential to improve the lives of every patient and family we serve. We remain singularly focused on my, and our, goal to end blood cancers and disorders entirely."

Highlights of the high-impact science from Rutgers Cancer Institute at ASH (Free ASH Whitepaper) 2024:

Data from a study that leverages big data to improve prognostication in advanced stage classic Hodgkin Lymphoma (cHL). This study, which analyzed 1,240 patients, used multistate modeling (MSM) and individual patient data from the HoLISTIC Consortium to refine prognostication across the cHL disease course, through specifically assessing the relationships between Advanced Stage Hodgkin Lymphoma International Prognostication Index (A-HIPI), interim PET (iPET) and end of treatment (EOT) response, and whether the A-HIPI and iPET provide independent prognostic information.

Researchers examined the bispecific antibody linvoseltamab in patients with relapsed/refractory multiple myeloma (RRMM), assessing longer follow-up and a select high-risk subgroup analysis of the Linker-MM1 study. Additional analyses were conducted to evaluate the effectiveness of linvoseltamab, focusing on how long patients responded to treatment (duration of response), how long they remained free from disease progression (progression-free survival), and their overall survival. These results, based on a safety follow-up period of over 14 months, were specifically looked at in high-risk patient groups.

A primary analysis from the ELM-1 expansion cohort, evaluated the efficacy and safety of the bispecific antibody odronextamab monotherapy in patients with diffuse large b-cell lymphoma (DLBCL) who had disease progression after CAR T-cell therapy. The primary endpoint was objective response rate, as assessed by independent central review according to the Lugano classification. The key secondary endpoints included duration of response, progression-free survival, and overall survival. Exploratory endpoints included immune biomarker assessment.
A study leveraging real-world evidence compared the overall survival associated with different treatment sequences in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in the United States. The study used an electronic health record database from Flatiron Health to identify adult patients with CLL or SLL who started treatment in 2016 or later and had received at least two lines of therapy.
An evaluation of CAR-HEMATOTOX scoring as a predictor of infection risk following treatment with odronextamab in relapsed/refractory (R/R) diffuse large b-cell lymphoma (DLBCL) and in follicular lymphoma (FL). These retrospective analysis of the ELM-1 and ELM-2 studies evaluated infections in 219 patients receiving odronextamab monotherapy for R/R DLBCL and FL, respectively.

On December 4, 2024 Rgenta Therapeutics, a clinical-stage biotechnology company pioneering the development of a new class of oral small molecules targeting RNA for oncology and neurological disorders, reported that it has entered into a multi-year, multi-target strategic research alliance with GSK (Press release, Rgenta Therapeutics, DEC 4, 2024, View Source [SID1234648808]). The alliance aims to advance the discovery and development of novel RNA-targeted small molecule splice modulators for multiple disease areas including oncology.

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"We are excited about Rgenta’s differentiated approach to discover and develop oral small molecule splice modulators for high-value targets," said Christopher Austin, M.D., SVP Research Technologies at GSK. "We are dedicated to partnering with leading companies to complement our existing expertise in RNA-targeting medicines and look forward to advancing this promising modality to more patients with difficult-to-treat diseases."

"We are thrilled to have GSK, a leading biopharma company, as our partner. This alliance further validates the potential of Rgenta’s small molecule RNA-targeting drug discovery platform," said Simon Xi, Ph.D., co-founder and chief executive officer of Rgenta. "Together we have the potential to accelerate the development of a new class of medicines that can provide new therapeutic options for patients."

Under the terms of the agreement, Rgenta will receive up to $46 million in a cash upfront and pre-option milestone payments. Rgenta has the potential to receive up to nearly $500 million per target in option exercise, research, development, regulatory, and commercial milestone payments plus tiered royalties and a future equity investment. GSK also has an option to expand the alliance to include additional targets. Under the alliance, Rgenta will use its proprietary discovery platform to develop novel oral RNA-targeting small molecule splice modulators against multiple targets nominated by GSK for development. Following GSK’s exercise of its options, GSK will be responsible for further development and commercialization of any drug candidates that arise from the alliance.

Travis Wager, Ph.D. co-founder, president and chief scientific officer of Rgenta added, "We are excited to partner with GSK, whose science-driven philosophy and successful track record of harnessing scientific innovation to benefit patients aligns perfectly with our mission. This alliance additionally validates our discovery platform which has already led to our first clinical stage asset, RGT-61159, an orally available small molecule designed to specifically modulate splicing of the transcription factor MYB."

On December 4, 2024 Phanes Therapeutics, Inc. (Phanes), a clinical stage biotech company focused on innovative drug discovery and development in oncology, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to PT217 for the treatment of patients with metastatic de novo or treatment-emergent neuroendocrine prostate cancer (NEPC) (Press release, Phanes Therapeutics, DEC 4, 2024, View Source [SID1234648807]). This is the second Fast Track Designation granted to PT217 by the FDA. Earlier this year, PT217 was granted Fast Track designation for extensive-stage small cell lung cancer (ES-SCLC) with disease progression following platinum chemotherapy with or without a checkpoint inhibitor by the agency.

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PT217, a first-in-class native IgG-like bispecific antibody (bsAb) targeting DLL3 and CD47, is being developed for the treatment of patients with small cell lung cancer (SCLC) and neuroendocrine carcinoma, including neuroendocrine prostate cancer (NEPC). In addition to Fast Track designation, PT217 was also granted orphan drug designations for the treatment of small cell lung cancer and neuroendocrine carcinoma (NEC), respectively.

The multi-center Phase I/II clinical trial of PT217 (NCT05652686), known as the SKYBRIDGE study, is currently evaluating the safety, tolerability, pharmacokinetics and preliminary efficacy of PT217 in patients with advanced or refractory cancers expressing DLL3. A Phase I clinical trial of PT217 is also ongoing in China (CTR20242720). Earlier this year, Phanes entered into a clinical supply agreement with Roche to study PT217 in combination with Roche’s anti-PD-L1 therapy, atezolizumab.

On December 4, 2024 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported that it will host a webcast on Wednesday, December 11, 2024, at 4:30 p.m. ET / 9:30 p.m. GMT to provide an overview of clinical data, patient need and commercialization strategy for Ziihera (zanidatamab-hrii), the first chemotherapy-free dual HER2-targeted bispecific antibody indicated for biliary tract cancer (BTC) (Press release, Jazz Pharmaceuticals, DEC 4, 2024, View Source [SID1234648806]). Ziihera was approved under accelerated approval by the U.S. Food and Drug Administration (FDA) on November 20, 2024, for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) BTC, as detected by an FDA-approved test.1

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Jazz senior management will provide an overview of Ziihera and commercial launch plans, and Dr. Shubham Pant will discuss previously disclosed BTC data from the HERIZON-BTC-01 trial. Shubham Pant, M.D., MBBS, is a professor in the Department of Gastrointestinal Medical Oncology with a joint appointment in the Department of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center.

Audio webcast/conference call:
U.S. Dial-In Number: +1 800 715 9871
Ireland Dial-In Number: +353 1800 943 926
Additional global dial-in numbers are available here.
Passcode: 4898380

Interested parties may access the live audio webcast via the Investors section of the Jazz Pharmaceuticals website at View Source To ensure a timely connection, it is recommended that participants register at least 15 minutes prior to the scheduled webcast.

A replay of the webcast will be available via the Investors section of the Jazz Pharmaceuticals website at View Source

About Ziihera (zanidatamab-hrii)
Ziihera (zanidatamab-hrii) is a bispecific HER2-directed antibody that binds to two extracellular sites on HER2. Binding of zanidatamab-hrii with HER2 results in internalization leading to a reduction of the receptor on the tumor cell surface. Zanidatamab-hrii induces complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). These mechanisms result in tumor growth inhibition and cell death in vitro and in vivo.1 In the United States, Ziihera is indicated for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer (BTC), as detected by an FDA-approved test.1 The U.S. Food and Drug Administration (FDA) granted accelerated approval for this indication based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).1

Zanidatamab is not approved anywhere else in the world.

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 FDA granted Breakthrough Therapy designation for zanidatamab development in patients with previously treated HER2 gene-amplified 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 1L 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.

Important Safety Information

WARNING: EMBRYO-FETAL TOXICITY
Exposure to ZIIHERA during pregnancy can cause embryo-fetal harm. Advise patients of the risk and need for effective contraception.

WARNINGS AND PRECAUTIONS

Embryo-Fetal Toxicity
ZIIHERA can cause fetal harm when administered to a pregnant woman. In literature reports, use of a HER2-directed antibody during pregnancy resulted in cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death.

Verify the pregnancy status of females of reproductive potential prior to the initiation of ZIIHERA. Advise pregnant women and females of reproductive potential that exposure to ZIIHERA during pregnancy or within 4 months prior to conception can result in fetal harm. Advise females of reproductive potential to use effective contraception during treatment with ZIIHERA and for 4 months following the last dose of ZIIHERA.

Left Ventricular Dysfunction

ZIIHERA can cause decreases in left ventricular ejection fraction (LVEF). LVEF declined by >10% and decreased to <50% in 4.3% of 233 patients. Left ventricular dysfunction (LVD) leading to permanent discontinuation of ZIIHERA was reported in 0.9% of patients. The median time to first occurrence of LVD was 5.6 months (range: 1.6 to 18.7). LVD resolved in 70% of patients.

Assess LVEF prior to initiation of ZIIHERA and at regular intervals during treatment. Withhold dose or permanently discontinue ZIIHERA based on severity of adverse reactions.

The safety of ZIIHERA has not been established in patients with a baseline ejection fraction that is below 50%.

Infusion-Related Reactions
ZIIHERA can cause infusion-related reactions (IRRs). An IRR was reported in 31% of 233 patients treated with ZIIHERA as a single agent in clinical studies, including Grade 3 (0.4%), and Grade 2 (25%). IRRs leading to permanent discontinuation of ZIIHERA were reported in 0.4% of patients. IRRs occurred on the first day of dosing in 28% of patients; 97% of IRRs resolved within one day.

Prior to each dose of ZIIHERA, administer premedications to prevent potential IRRs. Monitor patients for signs and symptoms of IRR during ZIIHERA administration and as clinically indicated after completion of infusion. Have medications and emergency equipment to treat IRRs available for immediate use.

If an IRR occurs, slow, or stop the infusion, and administer appropriate medical management. Monitor patients until complete resolution of signs and symptoms before resuming. Permanently discontinue ZIIHERA in patients with recurrent severe or life-threatening IRRs.

Diarrhea

ZIIHERA can cause severe diarrhea.

Diarrhea was reported in 48% of 233 patients treated in clinical studies, including Grade 3 (6%) and Grade 2 (17%). If diarrhea occurs, administer antidiarrheal treatment as clinically indicated. Perform diagnostic tests as clinically indicated to exclude other causes of diarrhea. Withhold or permanently discontinue ZIIHERA based on severity.

ADVERSE REACTIONS

Serious adverse reactions occurred in 53% of 80 patients with unresectable or metastatic HER2-positive BTC who received ZIIHERA. Serious adverse reactions in >2% of patients included biliary obstruction (15%), biliary tract infection (8%), sepsis (8%), pneumonia (5%), diarrhea (3.8%), gastric obstruction (3.8%), and fatigue (2.5%). A fatal adverse reaction of hepatic failure occurred in one patient who received ZIIHERA.

The most common adverse reactions in 80 patients with unresectable or metastatic HER2-positive BTC who received ZIIHERA (≥20%) were diarrhea (50%), infusion-related reaction (35%), abdominal pain (29%), and fatigue (24%).

USE IN SPECIFIC POPULATIONS

Pediatric Use

Safety and efficacy of ZIIHERA have not been established in pediatric patients.

Geriatric Use

Of the 80 patients who received ZIIHERA for unresectable or metastatic HER2-positive BTC, there were 39 (49%) patients 65 years of age and older. Thirty-seven (46%) were aged 65-74 years old and 2 (3%) were aged 75 years or older.

No overall differences in safety or efficacy were observed between these patients and younger adult patients.