Author: Wang, Li ; Chen, Juan ; Wan, Yan ; Zhang, Xingxia ; Bian, Meiru ; Si, Yejun ; Yang, Xiaotian ; Huang, Sailan ; Zhang, Yanming ; Hao, Ziyi ; Fei, Yingying ; Zhang, Bing ; Yu, Youhuan ; Lin, Guoqiang

OBJECTIVESRelapsed/refractory acute B-cell lymphoblastic leukemia (R/R B-ALL) often responds poorly to induction chemotherapy. However, recent research has shown a novel and effective drug treatment for R/R B-ALL.METHODSA total of eight patients with R/R B-ALL were enrolled in the study from November 2021 to August 2022. All patients received chemotherapy based on a combination regimen of venetoclax and azacitidine. The regimen was as follows venetoclax 100 mg d₁, 200 mg d₂, 400 mg d_3-14, azacitidine 75 mg/m² d_1-7.RESULTSFive of eight patients achieved very deep and complete remission (CR) with minimal residual disease (MRD) less than 0.1%. One patient achieved partial remission. Two patients did not achieve remission. There were no serious adverse events and all patients were well tolerated. Three patients were eligible for consolidation chemotherapy and were bridged to CAR-T therapy.CONCLUSIONSThe combined regimen of venetoclax and azacitidine may be beneficial for patients with R/R B-ALL.

31 Dec 2024·mAbs

In silico methods for immunogenicity risk assessment and human homology screening for therapeutic antibodies

Article

Author: Seshadri, Soorya ; Rosenberg, Amy S ; Mattei, Aimee E ; De Groot, Anne S ; Tivin, Jacob ; Gutierrez, Andres H ; Ardito, Matt ; Martin, William D

In silico immunogenicity risk assessment has been an important step in the development path for many biologic therapeutics, including monoclonal antibodies. Even if the source of a given biologic is 'fully human', T cell epitopes that are contained in the sequences of the biologic may activate the immune system, enabling the development of anti-drug antibodies that can reduce drug efficacy and may contribute to adverse events. Computational tools that identify T cell epitopes from primary amino acid sequences have been used to assess the immunogenic potential of therapeutic candidates for several decades. To facilitate larger scale analyses and accelerate preclinical immunogenicity risk assessment, our group developed an integrated web-based platform called ISPRI, (Immunogenicity Screening and Protein Re-engineering Interface) that provides hands-on access through a secure web-based interface for scientists working in large and mid-sized biotech companies in the US, Europe, and Japan. This toolkit has evolved and now contains an array of algorithms that can be used individually and/or consecutively for immunogenicity assessment and protein engineering. Most analyses start with the advanced epitope mapping tool (EpiMatrix), then proceed to identify epitope clusters using ClustiMer, and then use a tool called JanusMatrix to define whether any of the T cell epitope clusters may generate a regulatory T cell response which may diminish or eliminate anti-drug antibody formation. Candidates can be compared to similar products on a normalized immunogenicity scale. Should modifications to the biologic sequence be an option, a tool for moderating putative immunogenicity by editing T cell epitopes out of the sequence is available (OptiMatrix). Although this perspective discusses the in-silico immunogenicity risk assessment for monoclonal antibodies, bi-specifics, multi-specifics, and antibody-drug conjugates, the analysis of additional therapeutic modalities such as enzyme replacement proteins, blood factor proteins, CAR-T, gene therapy products, and peptide drugs is also made available on the ISPRI platform.

31 Dec 2024·Journal of Medical Economics

An updated cost-effectiveness analysis of axicabtagene ciloleucel in second-line large B-cell lymphoma patients in the United States

Article

Author: Perales, Miguel-Angel ; Feng, Chaoling ; Blissett, Rob ; Johnston, Patrick B ; Patel, Anik R ; Vadgama, Sachin ; Dickinson, Michael ; Smith, Nathaniel J ; Oluwole, Olalekan O

AIMSThis economic evaluation of axicabtagene ciloleucel (axi-cel) versus previous standard of care (SOC; salvage chemotherapy followed by high-dose therapy with autologous stem cell rescue) in the second line (2L) large B-cell lymphoma population is an update of previous economic models that contained immature survival data.METHODSThis analysis is based on primary overall survival (OS) ZUMA-7 clinical trial data (median follow-up of 47.2 months), from a United States (US) payer perspective, with a model time horizon of 50 years. Mixture cure models were used to extrapolate updated survival data; subsequent treatment data and costs were updated. Patients who remained in the event-free survival state by 5 years were assumed to have achieved long-term remission and not require subsequent treatment.RESULTSSubstantial survival and quality of life benefits were observed despite 57% of patients in the SOC arm receiving subsequent cellular therapy: median model-projected (ZUMA-7 trial Kaplan-Meier estimated) OS was 78 months (median not reached) for axi-cel versus 25 months (31 months) for SOC, resulting in incremental quality-adjusted life year (QALY) difference of 1.63 in favor of axi-cel. Incrementally higher subsequent treatment costs were observed in the SOC arm due to substantial crossover to cellular therapies, thus, when considering the generally accepted willingness to pay threshold of $150,000 per QALY in the US, axi-cel was cost-effective with an incremental cost-effectiveness ratio of $98,040 per QALY.CONCLUSIONSResults remained consistent across a wide range of sensitivity and scenario analysis, including a crossover adjusted analysis, suggesting that the mature OS data has significantly reduced the uncertainty of axi-cel's cost-effectiveness in the 2L setting in the US. Deferring treatment with CAR T therapies after attempting a path to transplant may result in excess mortality, lower quality of life and would be an inefficient use of resources relative to 2L axi-cel.

126

News (Medical) associated with CAR-T(Inceptor Bio)

07 Jun 2024

·www.fiercepharma.com

Fierce Pharma Asia—Enhertu's encore; Akeso's showstopper; GenScript and Legend's US scrutiny

Several Asian biopharma companies made waves at the American Society of Clinical Oncology annual meeting in Chicago. AstraZeneca and Daiichi Sankyo are looking at moving their antibody-drug conjugate Enhertu into another new breast cancer patient class. Ahead of the American Society of Clinical Oncology annual meeting, a cancer antibody from Akeso and Summit Therapeutics stole the show. More Chinese biopharma players are coming under scrutiny from U.S. lawmakers. Plus more. 1. ASCO: AstraZeneca, Daiichi's Enhertu looks to make history again in HER2-ultralow breast cancer After AstraZeneca and Daiichi Sankyo's Enhertu pioneered the HER2-low category in breast cancer treatment, the partners ignited discussion around the "HER2-ultralow" treatment category at this year's American Society of Clinical Oncology meeting. In a subgroup analysis of the DESTINY-Breast06 trial, Enhertu cut the risk of disease progression or death by 22% versus chemo in certain "HER2-ultralow" patients. The number didn't bear statistical significance. Company executives expressed excitement about the results while experts raised questions about identifying the right patients. 2. Akeso, Summit's Keytruda win draws 'explosive' interest at ASCO. But what does Merck think? On the eve of the American Society of Clinical Oncology's (ASCO's) annual meeting, Akeso and Summit Therapeutics' ivonescimab essentially stole the show with data demonstrating the partners' medicine beat Merck & Co.'s Keytruda in a head-to-head phase 3 trial in lung cancer on the endpoint of progression-free survival. In an interview with Fierce Pharma, Merck's chief medical officer Eliav Barr, M.D., said that overall survival results will remain key as the story plays out. Still, the results elicited a strong response at the ASCO conference. 3. Lawmakers request intelligence briefing on CDMO GenScript, Legend Biotech's ties to China As a U.S. biosecurity crackdown rolls on, two House lawmakers requested FBI director Christopher Wray and U.S. director of national intelligence Avril Haines provide a briefing on the CDMO GenScript and several of its subsidiaries, including the cell therapy specialist Legend Biotech. The lawmakers didn't allege any illicit behavior, but they said the companies' actions "underscore the need for vigilance in safeguarding U.S. competitiveness." 4. ASCO: AstraZeneca, AbelZeta’s solid tumor CAR-T shows promise in early trial (Release) Sino-American biotech AbelZeta, along with multinational AstraZeneca, had their own update to share at the American Society of Clinical Oncology event. In a small study in patients with heavily pretreated advanced hepatocellular carcinoma, the companies' solid tumor CAR-T drug C-CAR031 delivered promising early results. Among 23 study participants who could be evaluated, 91% experienced reductions in the size of their tumors. The data "provide compelling proof-of-concept to potentially redefine therapeutic paradigms" in hepatocellular carcinoma and certain other cancers, AbelZeta CEO Tony (Bizuo) Liu said in a statement. 5. FDA cracks down on China's Hengrui in scathing manufacturing write-up After an inspection early this year, the FDA handed China's Jiangsu Hengrui Pharmaceuticals a Form 483 manufacturing reprimand with eight observations. Among the agency's findings, the FDA said the company failed to make production records readily available and that it failed to establish adequate sterilization processes. While the company recently received an FDA rejection on an approval application, the manufacturing findings were not related to that decision, a Hengrui spokesperson said. Even though the inspection happened in January, the FDA just posted the Form 483 document this week. 6. South Korea, Japan, India and others form pharma alliance (Yonhap News Agency) Several large countries, including South Korea, Japan, India and the U.S., formed an alliance to bolster the global pharmaceutical supply chain, Yonhap News Agency reports. Dubbed the Biopharmaceutical Alliance, the group met this week at the BIO convention in San Diego. The participants, which include government officials and biopharma industry representatives, pledged to work together on policies and regulations to advance their effort, the news service reports. Other News of Note: 7. Otsuka mauled by ad body for 'unacceptable' transparency failing 8. Lotte Biologics, Merck KGaA ink partnership deal for biopharma production 9. Otsuka, Lundbeck run CGI Abilify ad in promotional push for long-acting bipolar drug 10. Sun Pharma brightens up Ilumya promos with psoriasis campaign encouraging self-love

Clinical ResultASCOPhase 3Cell Therapy

25 Apr 2024

·www.fiercepharma.com

Bristol Myers Squibb leans on long-term growth drivers, strategy overhaul to dodge IRA impacts

Bristol Myers Squibb's biggest upcoming challenge will come from Inflation Reduction Act impacts to Pfizer-partner blood thinner Eliquis. Facing pressure from the Inflation Reduction Act (IRA) and falling sales for CAR-T therapy Abecma, Bristol Myers Squibb CEO Chris Boerner, Ph.D., still says the Breyanzi-maker had a "good start" with the first quarter, thanks to a 5% sales jump and $11.9 billion in total revenue. The company is looking to compensate for coming 2026 impact from the ongoing IRA-price setting negotiations on Pfizer-partnered blood thinner Eliquis with its growth portfolio, which includes 11 key brands. BMS’ revenue composition is “rapidly transitioning” to favor the growth portfolio, according to a first-quarter earnings presentation (PDF). Looking further ahead, the drugmaker's long-term growth profile was boosted by the completion of two end-of-2023 deals to buy Karuna Therapeutics and RayzeBio. Earlier in the year, BMS also bought Mirati Therapeutics and signed a licensing deal with SystImmune. The crown jewel of the $14 billion Karuna deal was schizophrenia candidate KarXT, which the FDA is set to decide on in late September. BMS has repeatedly described the med as a multibillion-dollar opportunity and is already busy preparing for the launch. In the meantime, the company is working through falling sales of CAR-T therapy Abecma, which is partnered with 2seventy bio, and upcoming IRA impacts on Eliquis. Abecma sales fell 56% year over year to $52 million in the U.S. and 44% year over year to $82 million worldwide. Still, recent nods in Europe and the U.S. for relapsed and refractory multiple myeloma in patients who have received at least two specific prior therapies could offer promise. The New York pharma's other CAR-T, Breyanzi, looks set for solid growth with a much wider patient pool coming from a recent nod for previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma and upcoming FDA decisions in follicular lymphoma and mantle cell lymphoma. Both meds will benefit from a recently expanded partnership with South San Francisco manufacturer Cellares, reserving further CAR-T manufacturing space across the globe. But BMS is one of many Big Pharmas that could be affected by supply disruptions from the U.S. government’s mission to crack down on relations with Chinese manufacturing firms. The company is plotting contingency plans to “protect the continuity of supply,” BMS Chief Financial Officer Davie Elkins told the Financial Times. BMS leans on China’s WuXi Biologics to produce some of the active pharmaceutical ingredients that comprise Revlimid. Over in the legacy portfolio, Eliquis added $7.1 billion to BMS’ total revenue. Off-patent multiple myeloma med Revlimid, meanwhile, had a 5% global decline to $1.7 billion. With the earnings report, the company announced a “strategic productivity initiative” to save $1.5 billion by the end of 2025. The move entails a focus on R&D programs with potential for the greatest return on investment, prioritization of key growth brands and optimizing operations. The overhaul will result in a total workforce cut to about 2,000 employees during 2024. The layoffs include teams in Washington state and staffers working on Breyanzi, Fierce Biotech reported from sources familiar with the decision.

License out/inAcquisition

22 Apr 2024

·firstwordpharma.com

EU clears J&J's myeloma cell therapy Carvykti for second-line use

Regulators in the EU have approved Johnson & Johnson and Legend Biotech's Carvykti (ciltacabtagene autoleucel) for patients with relapsed and refractory multiple myeloma who have received at least one prior line of therapy.The decision comes shortly after US regulators expanded the BCMA-directed CAR-T drug's label for the same indication.Carvykti was first granted a conditional marketing authorisation in Europe in 2022 in the fourth-line setting, backed by the Phase Ib/II CARTITUDE-1 study.The latest approval was based on the Phase III CARTITUDE-4 trial, which evaluated Carvykti versus standard regimens in adults with relapsed and lenalidomide-refractory multiple myeloma who had received one to three prior lines of therapy. A single infusion of Carvykti reduced the risk of disease progression or death by 59% compared to standard regimens, meeting the primary endpoint.Jordan Schecter, disease area leader for multiple myeloma at Johnson & Johnson, said the drug "is an important part of how we are working to redefine multiple myeloma and ultimately achieve sustained remissions for patients."Bristol Myers Squibb's competing CAR-T Abecma (idecabtagene vicleucel) beat Carvykti to a broader EU label by about a month, although it was cleared for use in the third-line setting. Concerns about early deaths have been flagged for both treatments.Meanwhile, Johnson & Johnson touted Carvykti as one of its stronger oncology performers so far this year, generating $157 million in sales during the first quarter, more than double the corresponding year-ago period. However, that still missed consensus of $200 million for the product. For more, see Vital Signs: Bispecifics challenge CAR-T in the BCMA revenue race.

Drug ApprovalPhase 3Cell TherapyClinical ResultImmunotherapy

100 Deals associated with CAR-T(Inceptor Bio)

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	Preclinical	US	Inceptor Bio LLCStartup	20 May 2022

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

CAR-T(Inceptor Bio)

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation