- |||||||||| Journal: Antibodies to watch in 2024. (Pubmed Central) - Jan 9, 2024
In this installment, we discuss key details for 16 antibody therapeutics granted a first approval in 2023, as of November 17 (lecanemab (Leqembi), rozanolixizumab (RYSTIGGO), pozelimab (VEOPOZ), mirikizumab (Omvoh), talquetamab (Talvey), elranatamab (Elrexfio), epcoritamab (EPKINLY), glofitamab (COLUMVI), retifanlimab (Zynyz), concizumab (Alhemo), lebrikizumab (EBGLYSS), tafolecimab (SINTBILO), narlumosbart (Jinlitai), zuberitamab (Enrexib), adebrelimab (Arelili), and divozilimab (Ivlizi))...These nearly 50 product candidates include numerous innovative bispecific antibodies, such as odronextamab, ivonescimab, linvoseltamab, zenocutuzumab, and erfonrilimab, and antibody-drug conjugates, such as trastuzumab botidotin, patritumab deruxtecan, datopotamab deruxtecan, and MRG002, as well as a mixture of two immunocytokines (bifikafusp alfa and onfekafusp alfa)...Our analyses indicate that these molecules have approval success rates in the range of 14-32%, with higher rates associated with antibodies developed for non-cancer indications. Overall, our data suggest that antibody therapeutic development efforts by the biopharmaceutical industry are robust and increasingly successful.
- |||||||||| Fetroja (cefiderocol) / Shionogi
Journal: Genomic characterization of an NDM-9-producing Acinetobacter baumannii clinical isolate and role of Glu152Lys substitution in the enhanced cefiderocol hydrolysis of NDM-9. (Pubmed Central) - Sep 13, 2023
Interestingly, steady-state kinetic parameters, measured using purified NDM-1 and NDM-9 (Glu152Lys) enzymes, revealed that the affinity for cefiderocol was 3-fold higher for NDM-9 (K?=?53??M) than for NDM-1 (K?=?161??M), leading to a 2-fold increase in catalytic efficiency for NDM-9 (0.13 and 0.069??M.s, for NDM-9 and NDM-1, respectively). Finally, we showed by molecular docking experiments that the residue 152 of NDM-like enzymes plays a key role in cefiderocol binding and resistance, by allowing a strong ionic interaction between the Lys152 residue of NDM-9 with both the Asp223 residue of NDM-9 and the carboxylate group of the R1 substituent of cefiderocol.
- |||||||||| A166 / Sichuan Kelun Pharma
Biomarker, Journal: Mutation analysis of the ECE1 gene in late-onset Alzheimer's disease. (Pubmed Central) - Jul 18, 2023
Moreover, there was no significant association between LOAD and non-synonymous rare damaging variants at the gene level. Our results suggest rare coding variants of ECE1 might not play an important role in AD risk in the Chinese population.
- |||||||||| A166 / Sichuan Kelun Pharma
P1 data, Journal, Metastases: Phase I study of A166, an antibody?drug conjugate in advanced HER2-expressing solid tumours. (Pubmed Central) - May 6, 2023
For all assessable HER2-positive breast cancer patients enroled in the 4.8?mg/kg and 6.0?mg/kg cohorts, the corresponding ORRs were 73.9% (17/23) and 68.6% (24/35), respectively, and the median PFS was 12.3 and 9.4 months, respectively. A166 has a recommended phase II dose of 4.8?mg/kg Q3W, manageable toxicity, good stability in the circulation and promising antitumour activities in HER2-positive breast cancer patients.
- |||||||||| trastuzumab rezetecan (SHR-A1811) / Jiangsu Hengrui Pharma
Safety, tolerability, pharmacokinetics, and antitumor activity of SHR-A1811 in HER2-expressing/mutated advanced solid tumors: A global phase 1, multi-center, first-in-human study (Section 45; Poster Board #7) - Mar 14, 2023 - Abstract #AACR2023AACR_5998;
Subgroup analyses of ORRNo. of prior treatment lines in metastatic setting in all pts (N=250)HER2 positive BC (N=108)HER2-low BC (N=77)Other tumor types (N=65)?381.8% (45/55)58.7% (27/46)36.7% (18/49)>381.1% (43/53)51.6% (16/31)31.3% (5/16)Prior anti-HER2 therapies in pts with BC (N=185)*HER2 positive BC (N=108)HER2-low BC (N=77)All BC (N=185)Any82.2% (88/107, 73.7-89.0)68.8% (11/16, 41.3-89.0)80.5% (99/123, 72.4-87.1)Trastuzumab81.9% (86/105, 73.2-88.7)75.0% (9/12, 42.8-94.5)81.2% (95/117, 72.9-87.8)Pertuzumab83.0% (39/47, 69.2-92.4)100% (5/5, 47.8-100)84.6% (44/52, 71.9-93.1)Pyrotinib86.9% (53/61, 75.8-94.1)71.4% (5/7, 29.0-96.3)85.3% (58/68, 74.6-92.7)Lapatinib80.0% (28/35, 63.1-91.6)100% (1/1, 2.5-100)80.6% (29/36, 64.0-91.8)T-DM182.4% (14/17, 56.6-96.2)100% (3/3, 29.2-100)85.0% (17/20, 62.1-96.8)Other HER2-ADC (except T-DM1)**60.0% (9/15, 32.3-83.7)50.0% (2/4, 6.8-93.2)57.9% (11/19, 33.5-79.8)ORR in pts with tumor types other than BC (N=65)HER2 IHC3+ or IHC2+/ISH+ (N=36)HER2 IHC2+/ISH- or IHC1+ or unknown (N=29)All other tumor types (N=65)% (n/N)38.9% (14/36)31.0% (9/29)35.4% (23/65)ORR was shown as % (n/N, 95% CI) or % (n/N).
- |||||||||| A166 / Sichuan Kelun Pharma
Journal: VO2max and Velocity at VO2max Play a Role in Ultradistance Trail-Running Performance. (Pubmed Central) - Mar 4, 2023
This is the first study to show that VO2max and velocity at VO2max are significant predictors of performance in a 166-km trail-running race. This suggests that ultratrail runners should focus on the development of these 2 qualities to optimize their race performance.
- |||||||||| A166 / Sichuan Kelun Pharma
Journal: Quantifying the impacts of 166 years of land cover change on lowland bird communities. (Pubmed Central) - May 26, 2022
Using these maps and a hierarchical community model of relationships between breeding bird abundance and land cover types, we estimated that broad-scale land cover change over a 166-year period was associated with more than 70% decline in both potential species richness and abundance of avian communities...Our results suggest that broad-scale land cover change for agriculture has led to drastic reductions in wetland and forest species and promoted changes in community composition in large parts of the Northern Hemisphere. This study provides potential baseline information that could inform future conservation policies.
- |||||||||| A166 / Sichuan Kelun Pharma
Updated results and biomarker analyses from the phase I trial of A166 in patients with HER2-expressing locally advanced or metastatic solid tumors. (Available On Demand; 415) - Apr 28, 2022 - Abstract #ASCO2022ASCO_1124;
Median age was 53.5 years (range 26-71), 58 pts (100%) had prior HER2-targeted therapy with the median lines of 4, including 100% received trastuzumab ± pertuzumab, 94.8% received anti-HER2 TKIs, and 20.7% received anti-HER2 ADCs in the metastatic setting. The previously demonstrated preliminary clinical benefit of A166-ADC was maintained with no new safety signals, which demonstrated manageable toxicity and encouraging anti-tumor activity in heavily pretreated HER2-positive metastatic breast cancer patients.
- |||||||||| A166 / Sichuan Kelun Pharma
Journal: Reversible HER2 antibody-drug conjugate-induced ocular toxicity. (Pubmed Central) - Apr 5, 2022
Combination therapy including aggressive lubrication, withholding drug, and ASTs help reverse toxicity. Recognizing that ADC-induced epitheliopathy can respond to ocular management may enable cancer patients to continue lifesaving therapy.
- |||||||||| Review, Journal: Antibody-Drug Conjugates Targeting the Human Epidermal Growth Factor Receptor Family in Cancers. (Pubmed Central) - Mar 18, 2022
In this review article, we summarize the three approved ADCs (T-DM1, DS-8201a and RC48), together with the investigational EGFR-directed ADCs (ABT-414, MRG003 and M1231), HER2-directed ADCs (SYD985, ARX-788, A166, MRG002, ALT-P7, GQ1001 and SBT6050) and HER3-directed ADC (U3-1402). Lastly, we discuss the major challenges associated with the development of ADCs, and highlight the possible future directions to tackle these challenges.
- |||||||||| A166 / Sichuan Kelun Pharma
[VIRTUAL] Improving Outcomes for Patients with Lupus Nephritis Through Early Diagnosis and Self-management (Room 2) - Sep 21, 2021 - Abstract #ACRCONVERGENCE2021ACR_CONVERGENCE_289;
In health care systems that are under-resourced, the work of Not-For-Profit associations can support patient care at no cost to the hospital or patients.Location: Barbados is a 166 square island with a population of 280,000 (95% Afro-Caribbean) served by one hospital and one rheumatologist...Late presentations and need for hospitalization have begun to decline.Providing objective documentation of blood pressure control, and optimal blood pressure control in lupus nephritis reduces the rate of progression to end stage renal failure.Allowing opportunity of observing patient engagement in their health care- those who regularly input information onto the health portal are often positively engaged in their healthcare. Conversely those who fail to check-in to the portal may be neglecting their health in other ways such as medication non-adherence and can be contacted by email or telephone.This program, funded solely by donations and supported by volunteers, can be reproduced in settings that face similar challenges and provides a useful bridge between the hospital and the community.
- |||||||||| trastuzumab botidotin (A166) / Sichuan Kelun Pharma
Trial completion date, Trial primary completion date, Metastases: Study of A166 in Patients With Relapsed/Refractory Cancers Expressing HER2 Antigen or Having Amplified HER2 Gene (clinicaltrials.gov) - Sep 1, 2021
P1/2, N=82, Recruiting,
Conversely those who fail to check-in to the portal may be neglecting their health in other ways such as medication non-adherence and can be contacted by email or telephone.This program, funded solely by donations and supported by volunteers, can be reproduced in settings that face similar challenges and provides a useful bridge between the hospital and the community. Trial completion date: Dec 2021 --> Dec 2022 | Trial primary completion date: Apr 2021 --> Apr 2022
- |||||||||| A166 / Sichuan Kelun Pharma
Journal: Combining the production of L-lactic acid with the production of feed protein concentrates from alfalfa. (Pubmed Central) - Aug 28, 2021
The (residual) brown juice was investigated as source of nutrients for producing L-lactic acid from glucose or xylose with B. coagulans A107 or B. coagulans A166, respectively...Comparing different brown juices, initial green juice fermentation with B. coagulans is recommended if the brown juice is to be used for producing L-lactic acid. Based on our results, it is possible to combine protein recovery with lactic acid production, and the brown juice proved to be a good nutrient source for L-lactic acid production with high optical purities.
- |||||||||| A166 / Sichuan Kelun Pharma
Journal: A Multi-Variate Approach to Predicting Myoelectric Control Usability. (Pubmed Central) - Aug 12, 2021
A combination of two offline metrics (mean semi-principal axes and mean absolute value) significantly outperformed feature efficiency alone, with a 166% increase in the predicted R2 value (i.e., VEcv). These findings suggest that combinations of metrics could provide a more robust framework for predicting usability.
- |||||||||| A166 / Sichuan Kelun Pharma, Lagevrio (molnupiravir) / Emory University, Ridgeback Biotherap, Merck (MSD)
Journal: AI-guided discovery of the invariant host response to viral pandemics. (Pubmed Central) - Jul 3, 2021
The results will facilitate marker-assisted selection (MAS) introducing the qSCN18 locus from PI 567516C into high-yielding soybean cultivars with durable resistance to SCN. The ViP signatures provide a quantitative and qualitative framework for titrating the immune response in viral pandemics and may serve as a powerful unbiased tool to rapidly assess disease severity and vet candidate drugs.
- |||||||||| A166 / Sichuan Kelun Pharma
Journal: Rational-design engineering to create the flavin reductase variants with thermostable and solvent-tolerant properties. (Pubmed Central) - May 28, 2021
The 6-ns molecular dynamics (MD) simulations at 300-500 K indicated that mutations of A166 to L and A58 to P resulted in the structural change with increased stabilization of hydrophobic interactions, thus improving thermostability. Our findings demonstrated that the improvement in thermostability of C1 enzyme can lead to the broad-spectrum uses of C1 as a redox biocatalyst for future industrial applications.
- |||||||||| A166 / Sichuan Kelun Pharma
Journal: The role of protein hydrolysates in prolonging viability and enhancing antibody production of CHO cells. (Pubmed Central) - May 15, 2021
There were individual differences between hydrolysates in terms of enhancement of mAb productivity, the highest being a 166% increase of mAb titre (to 117 mg/L) in batch cultures of CHO-EG2 supplemented with UPcotton hydrolysate...• Cotton-based hydrolysates showed high bioactivity and potential for use in serum-free media. • Enhanced galactosylation and sialylation was shown for some of the Mabs tested.
- |||||||||| A166 / Sichuan Kelun Pharma
Journal: Survey Outcomes of Lipedema Reduction Surgery in the United States. (Pubmed Central) - Apr 30, 2021
Subjects were recruited and consented online for a 166-item questionnaire in REDCap...Women with lipedema noticed significant benefits after lipedema reduction surgery in the USA. Prospective studies are needed to assess benefits and complications after lipedema reduction surgery in the USA.
- |||||||||| A166 / Sichuan Kelun Pharma
Journal: The Complete Nucleotide Sequence of pZM3, a 1970 FIA:FIB:FII Plasmid Carrying Antibiotic Resistance and Virulence Determinants. (Pubmed Central) - Mar 10, 2021
The multiresistance plasmid, pZM3, from a 1970 Salmonella enterica serovar Wien isolate from Algeria represents the multiresistance FIme-type plasmids conferring resistance to ampicillin, chloramphenicol, kanamycin, neomycin, sulfonamides, streptomycin, spectinomycin, tetracycline, and mercuric ions circulating in the Middle East in the 1970s...pZM3 is a 166.8-kb plasmid with three replicons typed as FIA-1, FIB-1, and FII-1, consistent with other FIme plasmids...The backbone of pZM3 was found to be almost identical to that of pRSB225, recovered in Germany in 2013, and their resistance islands are in the same position. The pRSB225 resistance island has evolved in situ from the pZM3 configuration through an insertion, a replacement, and an inversion.
- |||||||||| trastuzumab botidotin (A166) / Sichuan Kelun Pharma
Trial completion date, Trial primary completion date, Metastases: Study of A166 in Patients With Relapsed/Refractory Cancers Expressing HER2 Antigen or Having Amplified HER2 Gene (clinicaltrials.gov) - Jan 12, 2021
P1/2, N=82, Recruiting,
Our findings suggest that PLACT1 provides a novel epigenetic mechanism involved in constitutive activation of NF-κB signaling pathway and may represent a new therapeutic target of PDAC. Trial completion date: May 2021 --> Dec 2021 | Trial primary completion date: Oct 2020 --> Apr 2021
- |||||||||| A166 / Sichuan Kelun Pharma
Clinical, Journal: Induction of Labor in an Intubated Patient With Coronavirus Disease 2019 (COVID-19). (Pubmed Central) - Nov 3, 2020
The strongest predictor associated with mortality was a worse final FC (NYHA III-IV). Critically ill patients requiring mechanical ventilation, in this case due to COVID-19, may undergo induction of labor and vaginal delivery when carefully selected.
- |||||||||| A166 / Sichuan Kelun Pharma
Journal: Characterization of pUL5, an HCMV protein interacting with the cellular protein IQGAP1. (Pubmed Central) - Sep 8, 2020
The protein was predicted as a 166-amino-acid membrane protein with a theoretical mass of 19 kDa...Confocal microscopy analysis showed that pUL5 localized within the assembly compartment, but is not incorporated in the virion, as shown by Western blot on purified viral particles. Finally, pull-down experiments coupled with mass spectrometry analysis identified IQGAP1 as a pUL5 interactor, giving new hints on possible roles of pUL5 during HCMV infection.
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