Bio-Path Holdings Outlines Rationale for Development of BP1001-A as Potential Treatment for Obesity in Type 2 Diabetes Patients
Bio-Path Holdings (NASDAQ:BPTH) has outlined its strategic focus on developing BP1001-A as a potential treatment for obesity in Type 2 diabetes patients. The company's decision is based on scientific evidence suggesting that downregulating growth factor receptor-bound protein 2 (Grb2) could help lower blood glucose levels by affecting insulin signaling.
The company is conducting confirmatory preclinical studies and plans to complete IND-enabling testing in Q4 2024. Simultaneously, Bio-Path announced the discontinuation of its Phase 1 clinical trial of BP1002 for refractory/relapsed lymphoma and chronic lymphocytic leukemia due to enrollment challenges in these niche indications.
Bio-Path Holdings (NASDAQ:BPTH) ha delineato il suo focus strategico nello sviluppo di BP1001-A come potenziale trattamento per l'obesità nei pazienti affetti da diabete di tipo 2. La decisione dell'azienda si basa su evidenze scientifiche che suggeriscono che la riduzione della proteina legata al recettore del fattore di crescita 2 (Grb2) potrebbe contribuire ad abbassare i livelli di glucosio nel sangue influenzando la segnalazione dell'insulina.
L'azienda sta conducendo studi preclinici confermativi e prevede di completare i test di abilitazione dell'IND nel quarto trimestre del 2024. Allo stesso tempo, Bio-Path ha annunciato la cessazione della sua fase 1 dello studio clinico di BP1002 per linfoma refrattario/recidivante e leucemia linfatica cronica a causa di difficoltà di reclutamento in queste indicazioni di nicchia.
Bio-Path Holdings (NASDAQ:BPTH) ha delineado su enfoque estratégico en el desarrollo de BP1001-A como un tratamiento potencial para la obesidad en pacientes con diabetes tipo 2. La decisión de la compañía se basa en evidencia científica que sugiere que la regulación a la baja de la proteína unida al receptor del factor de crecimiento 2 (Grb2) podría ayudar a disminuir los niveles de glucosa en sangre al afectar la señalización de insulina.
La empresa está llevando a cabo estudios preclínicos de confirmación y planea completar las pruebas de habilitación de IND en el cuarto trimestre de 2024. Al mismo tiempo, Bio-Path anunció la interrupción de su ensayo clínico de fase 1 de BP1002 para linfoma refractario/recidivante y leucemia linfocítica crónica debido a desafíos en el reclutamiento en estas indicaciones de nicho.
Bio-Path Holdings (NASDAQ:BPTH)는 제2형 당뇨병 환자의 비만 치료를 위한 잠재적 치료제로 BP1001-A 개발에 대한 전략적 초점을 설정했습니다. 회사의 결정은 성장 인자 수용체 결합 단백질 2 (Grb2)의 발현을 감소시키는 것이 인슐린 신호 전달에 영향을 미쳐 혈당 수치를 낮추는 데 도움이 될 수 있다는 과학적 증거에 기반하고 있습니다.
회사는 확인 전임상 연구를 수행 중이며, 2024년 4분기까지 IND 승인에 필요한 테스트를 완료할 계획입니다. 동시에 Bio-Path는 특별한 모집 문제로 인해 BP1002의 재발성 림프종 및 만성 림프구 백혈병에 대한 1상 임상 시험의 중단을 발표했습니다.
Bio-Path Holdings (NASDAQ:BPTH) a défini son orientation stratégique sur le développement de BP1001-A en tant que traitement potentiel de l'obésité chez les patients atteints de diabète de type 2. La décision de l'entreprise repose sur des preuves scientifiques suggérant que la régulation à la baisse de la protéine de liaison au récepteur du facteur de croissance 2 (Grb2) pourrait aider à abaisser les niveaux de glucose dans le sang en influençant la signalisation de l'insuline.
L'entreprise réalise des études précliniques de confirmation et prévoit de compléter les tests d'habilitation IND au quatrième trimestre de 2024. Parallèlement, Bio-Path a annoncé l'arrêt de son essai clinique de phase 1 de BP1002 pour le lymphome réfractaire/récidivant et la leucémie lymphocytaire chronique, en raison de défis de recrutement dans ces indications de niche.
Bio-Path Holdings (NASDAQ:BPTH) hat seinen strategischen Fokus auf die Entwicklung von BP1001-A als potenzielle Behandlung von Adipositas bei Patienten mit Typ-2-Diabetes gesetzt. Die Entscheidung des Unternehmens basiert auf wissenschaftlichen Erkenntnissen, die darauf hindeuten, dass die Herabregulierung des wachstumsfaktor-bindenden Proteins 2 (Grb2) dazu beitragen könnte, die Blutzuckerwerte durch Beeinflussung der Insulsignalisierung zu senken.
Das Unternehmen führt bestätigende präklinische Studien durch und plant, die IND-erlaubenden Tests im 4. Quartal 2024 abzuschließen. Gleichzeitig gab Bio-Path die Einstellung seiner Phase-1-Studie zu BP1002 für refraktäre/rezidivierende Lymphome und chronische lymphatische Leukämie aufgrund von Rekrutierungsherausforderungen in diesen Nischenindikationen bekannt.
- Scientific evidence supports BP1001-A's potential effectiveness in treating obesity and Type 2 diabetes
- IND-enabling testing for BP1001-A scheduled for completion in Q4 2024
- BP1001-A has demonstrated safety and tolerability in multiple human clinical studies
- Discontinuation of Phase 1 trial for BP1002 due to enrollment challenges
- Competitive landscape in lymphoma and leukemia treatment affecting trial recruitment
- Resource reallocation required from existing programs to new metabolic focus
Insights
The strategic pivot to develop BP1001-A for obesity in Type 2 diabetes represents a significant shift in Bio-Path's pipeline focus. The scientific rationale is compelling, with Grb2 protein inhibition showing promise in enhancing insulin sensitivity and glucose uptake. Key preclinical evidence, including studies in Grb2 knockout mice and cell models, suggests BP1001-A could improve metabolic outcomes through its DNAbilize® delivery platform.
However, this decision comes with notable risks. The metabolic disease market is highly competitive and while BP1001-A's mechanism differs from current GLP-1 agonists, proving superior efficacy will be crucial. The discontinuation of the BP1002 lymphoma program also indicates resource constraints, making successful execution of this new direction critical for the company's future.
This strategic repositioning has mixed implications for Bio-Path's market prospects. While the obesity/diabetes market presents a massive commercial opportunity worth billions, entering this space means competing with established players like Novo Nordisk and Eli Lilly. The company's micro-cap status (
The discontinuation of the BP1002 program, while pragmatic given enrollment challenges, removes a near-term catalyst. Success in the metabolic space will require significant capital investment and likely strategic partnerships. Investors should monitor upcoming IND-enabling studies in Q4 2024 as a critical milestone.
Extensive Scientific Evidence Supporting Growth Factor Receptor Bound Protein-2 (Grb2) as Fundamental Link in Insulin Resistance
Reallocates Resources to Metabolic Program and Discontinues Enrollment in Phase 1 Study of BP1002 to Treat Relapsed/Refractory Lymphoma and Relapsed/Refractory Chronic Lymphocytic Leukemia Due to Enrollment Challenges in Niche Patient Populations
HOUSTON, Dec. 11, 2024 (GLOBE NEWSWIRE) -- Bio-Path Holdings, Inc., (NASDAQ:BPTH), a biotechnology company leveraging its proprietary DNAbilize® liposomal delivery and antisense technology to develop a portfolio of targeted nucleic acid cancer drugs, today outlined the growing body of scientific evidence that Bio-Path believes supports the development of BP1001-A for the treatment for obesity and related metabolic diseases in Type 2 diabetes patients.
Patients diagnosed with Type 2 diabetes are at high risk of developing life-threatening co-morbidities and often experience a poor quality of life. Lowering blood glucose levels is the principal goal in the treatment of patients with Type 2 diabetes. Scientific evidence suggests that by downregulating growth factor receptor-bound protein 2 (Grb2) expression, BP1001-A could help lower blood glucose level by affecting insulin signaling. Specifically, this cascade of events is led by decreasing insulin-induced mitogenic events and increasing insulin-induced metabolic events, thus leading to enhanced glucose internalization and storage. Bio-Path is conducting confirmatory preclinical studies to determine the effectiveness of BP1001-A in affecting insulin signaling and its potential as a therapeutic treatment for obese patients who have Type 2 diabetes.
“The rationale for initiating our development program for BP1001-A for the treatment of obesity is rooted in substantial scientific literature providing evidence that downregulating Grb2 expression affects insulin signaling, ultimately, leads to lower blood glucose levels. BP1001-A has been shown to downregulate Grb2 expression in preclinical models and has been shown to be safe and well-tolerated across a multitude of human clinical studies, giving us confidence in its potential to treat Type 2 diabetes and obesity,” said Peter H. Nielsen, President and Chief Executive Officer of Bio-Path. “We look forward to completing Investigational New Drug (IND)-enabling testing in the fourth quarter of 2024 and to advancing this important metabolic program in 2025.”
Scientific Rationale for BP1001-A for Treatment of Obesity – Patients diagnosed with Type 2 diabetes are at high risk of developing life-threatening co-morbidities and a poorer quality of life. Lowering blood glucose level is the principal goal in the treatment of patients with Type 2 diabetes. One potential method to manage Type 2 diabetes is to reduce body weight (Lingvay et al., 2022). Much success in weight loss has been reported for obese patients who are taking weight loss medication (Wilding et al., 2021; Frias et al., 2021). However, these medications are not as effective in inducing weight loss in obese patients who have Type 2 diabetes (Ghusn et al., 2022; Lingvay et al., 2022). Therefore, an alternative method of lowering blood glucose level is still needed for obese patients who have Type 2 diabetes.
Insulin lowers blood glucose level by activating the phosphoinositol-3 kinase (PI3K)/AKT pathway (Huang et al., 2018; Lee et al., 2022; Asiri et al., 2024). However, this insulin pathway is dysfunctional in obese patients who have Type 2 diabetes (Huang et al., 2018; Lee et al., 2022; Asiri et al., 2024). Literature suggests that Grb2 is an inhibitor of the insulin/PI3K/AKT pathway (Liu et al., 2009; Bhat et al., 2020; Ma et al., 2024). Upregulation of the Grb2 gene has been reported for patients with Type 2 diabetes (Bhat et al., 2020; Kumar et al., 2020; Alur et al., 2023). Knockdown of Grb2 expression enhanced insulin-induced AKT activity and glucose uptake in myoblasts and hepatoma cells (Liu et al., 2009; Shen et al., 2013). Furthermore, insulin sensitivity was restored in Grb2 heterozygous knockout mice fed on high fat-induced diet (Liu et al., 2009).
BP1001-A was designed to suppress Grb2 protein expression (Lara et al., 2020; Gagliardi and Tari Ashizawa, 2021). Bio-Path expects that by downregulating Grb2 expression, BP1001-A will lower blood glucose level by enhancing insulin-mediated AKT activation and glucose uptake and storage. Bio-Path is conducting preclinical studies to determine the effectiveness of BP1001-A in affecting insulin signaling and its potential as a therapeutic for obese patients who have Type 2 diabetes.
Resource Allocation – Separately, the Company announces its plans to reallocate resources toward its advancing metabolic program and to discontinue its Phase 1 clinical trial evaluating BP1002 as a treatment for refractory/relapsed lymphoma and refractory/relapsed chronic lymphocytic leukemia. This decision was based on enrollment challenges in these niche indications, particularly given the crowded development landscape that includes multiple competing trials.
About Bio-Path Holdings, Inc.
Bio-Path is a biotechnology company developing DNAbilize®, a novel technology that has yielded a pipeline of RNAi nanoparticle drugs that can be administered with a simple intravenous infusion. Bio-Path’s lead product candidate, prexigebersen (BP1001, targeting the Grb2 protein), is in a Phase 2 study for blood cancers, and BP1001-A, a drug product modification of prexigebersen, is in a Phase 1/1b study for solid tumors. The Company’s second product, BP1002, which targets the Bcl-2 protein, is being evaluated for the treatment of blood cancers and solid tumors, including acute myeloid leukemia. In addition, an IND application is expected to be filed for BP1003, a novel liposome-incorporated STAT3 antisense oligodeoxynucleotide developed by Bio-Path as a specific inhibitor of STAT3.
For more information, please visit the Company's website at http://www.biopathholdings.com.
Forward-Looking Statements
This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws. These statements are based on management's current expectations and accordingly are subject to uncertainty and changes in circumstances. Any express or implied statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Any statements that are not historical facts contained in this release are forward-looking statements that involve risks and uncertainties, including Bio-Path’s ability to raise needed additional capital on a timely basis in order for it to continue its operations, have success in the clinical development of its technologies, the timing of enrollment and release of data in such clinical studies, the accuracy of such data, limited patient populations of early stage clinical studies and the possibility that results from later stage clinical trials with much larger patient populations may not be consistent with earlier stage clinical trials, the maintenance of intellectual property rights, that patents relating to existing or future patent applications will be issued or that any issued patents will provide meaningful protection of our drug candidates, the impact, risks and uncertainties related to global pandemics, including the COVID-19 pandemic, and actions taken by governmental authorities or others in connection therewith, and such other risks which are identified in Bio-Path's most recent Annual Report on Form 10-K, in any subsequent quarterly reports on Form 10-Q and in other reports that Bio-Path files with the Securities and Exchange Commission from time to time. These documents are available on request from Bio-Path Holdings or at www.sec.gov. Bio-Path disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.
Contact Information:
Investors
Will O’Connor
Stern Investor Relations, Inc.
212-362-1200
will@sternir.com
Doug Morris
Investor Relations
Bio-Path Holdings, Inc.
832-742-1369
Cited Literature
Alur V, Raju V, Vastrad B, et al. Bioinformatics analysis of next generation sequencing data identifies molecular biomarkers associated with Type 2 diabetes mellitus. Clinical Medicine Insights: Endocrinology and Diabetes (2023) 16: 1–22.
Asiri A, Al Qarni A, Bakillah A. The interlinking metabolic association between type 2 diabetes mellitus and cancer: molecular mechanisms and therapeutic insights. Diagnostics (2024) 14: 2132. https://doi.org/10.3390/ diagnostics14192132
Bhat M, Pasini E, Das A, et al. Diabetogenic effects of immunosuppression: an integrative analysis. Transplantation (2020) 104: 211–221.
Frias JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med (2021) 385: 503-515. doi: 10.1056/NEJMoa2107519
Gagliardi M, Tari Ashizawa A. The challenges and strategies of antisense oligonucleotide drug delivery. Biomedicines (2021) 9: 433. doi: 10.3390/biomedicines9040433
Ghusn W, De la Rosa A, Sacoto D, et al. Weight loss outcomes associated with semaglutide treatment for patients with overweight or obesity. JAMA Network Open (2022) 5(9): e2231982. doi:10.1001/jamanetworkopen.2022.31982
Huang X, Liu G, Guo J, et al. The PI3K/AKT pathway in obesity and type 2 diabetes. Int J Biol Sci (2018) 14: 1483-1496. doi: 10.7150/ijbs.27173
Kumar U, Rajan B, Kumar T, et al. Involvement of essential signaling cascades and analysis of gene networks in diabesity. Genes (2020) 11: 1256. doi:10.3390/genes11111256
Lara OD, Bayraktar E, Amero P, et al. Therapeutic efficacy of liposomal Grb2 antisense oligodeoxynucleotide (L-Grb2) in preclinical models of ovarian and uterine cancer. Oncotarget (2020) 11: 2819-2833. doi: 10.18632/oncotarget.27667
Lee S-H, Park S-Y, Choi CS. Insulin resistance: from mechanisms to therapeutic strategies. Diabetes Metab J (2022) 46: 15-37. https://doi.org/10.4093/dmj.2021.0280
Lingvay I, Sumithran P, Cohen RV, et al. Obesity management as a primary treatment goal for type 2 diabetes: time to reframe the conversation. Lancet (2022) 399: 394–405. Published online September 30, 2021 https://doi.org/10.1016/ S0140-6736(21)01919-X
Liu X, Liu M, Zhang J, et al. Downregulation of Grb2 contributes to the insulin-sensitizing effect of calorie restriction. Am J Physiol Endocrinol Metab (2009) 296: E1067–E1075. First published February 24, 2009; doi:10.1152/ajpendo.90714.2008
Ma J, Dong Y, Liu J, et al. The role of GRB2 in diabetes, diabetes complications and related disorders. Diabetes Obes Metab (2024) 1–12. doi: 10.1111/dom.16015
Shen X, Miao Y, Feng R, et al. Suppression of Grb2 expression improved hepatic steatosis, oxidative stress, and apoptosis induced by palmitic acid in vitro partly through insulin signaling alteration. In Vitro Cellular and Developmental Biology (2013) 49: 576-582.
Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med (2021) 384: 989-1002. doi: 10.1056/NEJMoa2032183
FAQ
What is the scientific rationale behind BPTH's development of BP1001-A for obesity treatment?
When will BPTH complete IND-enabling testing for BP1001-A?
Why did BPTH discontinue the Phase 1 trial of BP1002?
What are the current development stages of BPTH's drug pipeline?
How does BP1001-A differ from existing obesity treatments for Type 2 diabetes patients?
