This is a phase I, open-label, study of BP1001-A in participants with advanced or recurrent solid tumors. The dose escalation phase will determine the safety and the maximum tolerated dose (MTD) or maximum administered dose (MAD) of BP1001-A as a single agent. After the MTD or MAD of BP1001-A is established, the dose expansion phase will commence and determine the safety, toxicity and response of BP1001-A in combination with paclitaxel.

Start Date19 Aug 2022

Sponsor / Collaborator

Bio-Path Holdings, Inc.

NCT02923986

/ WithdrawnPhase 1/2

A Phase Ib/IIa Single-arm, Open-label Clinical Trial to Evaluate the Safety, Pharmacokinetics, and Efficacy of BP1001 (a Liposomal Grb2 Antisense Oligonucleotide) in Combination With Dasatinib in Patients With Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia (CML) Including Chronic Phase Patients Who Have Failed Initial Tyrosine Kinase Inhibitor (TKI) Therapy, Accelerated or Blast Phase, Ph+ Acute Myeloid Leukemia (AML) or High-risk Ph+ Myelodysplastic Syndrome (MDS)

The primary objective of the Phase Ib study is to determine the dose-limiting toxicity (DLT) and maximal tolerated dose (MTD) of BP1001 in combination with dasatinib in patients with with Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia (CML) including chronic phase patients who have failed initial tyrosine kinase inhibitor (TKI) therapy, accelerated or blast phase, Ph+ Acute Myeloid Leukemia (AML) or High-risk Ph+ Myelodysplastic Syndrome (MDS). The primary objective of the Phase IIa study is to assess the efficacy of the combination of BP1001 and dasatinib in patients with Ph+ CML, Ph+AML, or high-risk Ph+ MDS.

Start Date01 Sep 2017

Sponsor / Collaborator

Bio-Path Holdings, Inc.

NCT02781883

/ RecruitingPhase 2

A Phase IIa, Open-label, Clinical Trial to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of BP1001 (a Liposomal Grb2 Antisense Oligonucleotide) in Combination With Venetoclax Plus Decitabine in Patients With AML Who Are Ineligible for Intensive Induction Therapy

The primary objectives of this study are to assess: (1) whether the combination of BP1001 plus venetoclax plus decitabine provides greater efficacy (Complete Remission [CR], Complete Remission with incomplete hematologic recovery [CRi], Complete Remission with partial hematologic recovery [CRh], than venetoclax plus decitabine alone (by historical comparison) in participants with untreated AML that cannot or elect not to be treated with more intensive chemotherapy; (2) whether BP1001-based treatment provides greater efficacy (CR, CRi, CRh) than intensive chemotherapy (by historical comparison) in participants with refractory/relapsed AML.

Start Date01 May 2016

Sponsor / Collaborator

Bio-Path Holdings, Inc.

100 Clinical Results associated with Prexigebersen

100 Translational Medicine associated with Prexigebersen

100 Patents (Medical) associated with Prexigebersen

Literatures (Medical) associated with Prexigebersen

21 Jul 2020·Oncotarget

Therapeutic efficacy of liposomal Grb2 antisense oligodeoxynucleotide (L-Grb2) in preclinical models of ovarian and uterine cancer

Article

Author: Wang, Ying ; Amero, Paola ; Bhattacharya, Pratip ; Ma, Shaolin ; Lara, Olivia D. ; Sood, Anil K. ; Hu, Wei ; Ivan, Cristina ; Ashizawa, Ana Tari ; Lopez-Berestein, Gabriel ; Dutta, Prasanta ; Bayraktar, Emine ; Rodriguez-Aguayo, Cristian ; Mangala, Lingegowda S.

BACKGROUND:

Adaptor proteins such as growth factor receptor-bound protein-2 (Grb2) play important roles in cancer cell signaling. In the present study, we examined the biological effects of liposomal antisense oligodeoxynucleotide that blocks Grb2 expression (L-Grb2) in gynecologic cancer models.

MATERIALS AND METHODS:

Murine orthotopic models of ovarian (OVCAR5 and SKOV3ip1) and uterine (Hec1a) cancer were used to study the biological effects of L-Grb2 on tumor growth. In vitro experiments (cell viability assay, Western blot analysis, siRNA transfection, and reverse phase protein array) were carried out to elucidate the mechanisms and potential predictors of tumor response to L-Grb2.

FINDINGS:

Treatment with L-Grb2 decreased tumor growth and metastasis in orthotopic models of ovarian cancer (OVCAR5, SKOV3ip1) by reducing angiogenesis and increasing apoptosis at a dose of 15 mg/kg with no effect on mouse body weight. Treatment with L-Grb2 and paclitaxel led to the greatest decrease in tumor weight (mean ± SEM, 0.17 g ± 0.10 g) compared with that in control mice (0.99 g ± 0.35 g). We also observed a reduction in tumor burden after treatment with L-Grb2 and the anti-VEGF antibody B-20 (86% decrease in tumor weight compared with that in controls). Ovarian cancer cells with ErbB2 amplification (OVCAR8 and SKOV3ip1) were the most sensitive to Grb2 downregulation. Reverse phase protein array analysis identified significant dysregulation of metabolites (LDHA, GAPDH, and TCA intermediates) in ovarian cancer cells after Grb2 downregulation.

INTERPRETATION:

L-Grb2 has therapeutic efficacy in preclinical models of ovarian and uterine cancer. These findings support further clinical development of L-Grb2.

01 Apr 2018·The Lancet. HaematologyQ1 · MEDICINE

Liposomal Grb2 antisense oligodeoxynucleotide (BP1001) in patients with refractory or relapsed haematological malignancies: a single-centre, open-label, dose-escalation, phase 1/1b trial

Q1 · MEDICINE

Article

Author: Pierce, Sherry ; Alvarado, Yesid ; Garcia-Manero, Guillermo ; Verstovsek, Srdan ; Wierda, William ; Lim, Miranda ; Kadia, Tapan ; Borthakur, Gautam ; Tari Ashizawa, Ana ; Pemmaraju, Naveen ; O'Brien, Susan ; Ravandi, Farhad ; Kantarjian, Hagop ; Ohanian, Maro ; Konopleva, Marina ; Jabbour, Elias ; Cortes, Jorge ; Andreeff, Michael

BACKGROUND:

Activating mutations of tyrosine kinases are common in leukaemias. Oncogenic tyrosine kinases use the growth factor receptor-bound protein 2 (Grb2) for signal transduction, leading to activation of mitogen-activated protein kinase (MAPK) 1 and MAPK3 (ERK2 and ERK1). We hypothesised that inhibition of Grb2 would suppress ERK1 and ERK2 activation and inhibit leukaemia progression. To inhibit Grb2, a liposome-incorporated antisense oligodeoxynucleotide that blocks Grb2 protein expression, BP1001, was developed. We report the first phase 1 findings of BP1001.

METHODS:

In this single-centre, open-label, dose-escalation phase 1/1b trial, we enrolled participants (aged ≥18 years) with refractory or relapsed acute myeloid leukaemia, Philadelphia-chromosome-positive chronic myeloid leukaemia (in chronic, accelerated, or blast phase), acute lymphoblastic leukaemia, or myelodysplastic syndrome, at MD Anderson Cancer Center (Houston, TX, USA). We used a 3 + 3 dose escalation strategy, with at least three patients enrolled at each dose level. We administered BP1001 intravenously, twice weekly, for 28 days, with a starting dose of 5 mg/m². If two or more patients developed toxic effects of grade 3 or higher, that dose level was deemed toxic. The dose was escalated if it did not produce dose-limiting toxic effects, and patients would be sequentially enrolled into cohort 2 (10 mg/m²), cohort 3 (20 mg/m²), cohort 4 (40 mg/m²), cohort 5 (60 mg/m²), or cohort 6 (90 mg/m²). After completion of monotherapy, we assessed the safety and toxicity of BP1001 (60 or 90 mg/m²) in combination with 20 mg low-dose cytarabine (twice-daily subcutaneous injections) in a phase 1b study in patients with refractory or relapsed acute myeloid leukaemia (ie, those who were refractory to at least one previous therapy regimen and no more than one previous salvage regimen). The objectives of this study were to establish the toxicity and tolerance of escalating doses of BP1001 monotherapy in patients with refractory or relapsed leukaemia, to assess the maximum tolerated dose of BP1001, and to determine the optimal biologically active dose of BP1001, defined as a 50% reduction in Grb2 expression in circulating leukaemia cells. We also aimed to assess the in-vivo pharmacokinetics of BP1001 and tumour response. The study is completed and is registered with ClinicalTrials.gov, number NCT01159028.

FINDINGS:

Between July 23, 2010, and Feb 23, 2016, we enrolled and treated 39 patients, of whom 27 were assessable for dose-limiting toxicity. The first patient treated had mucositis and hand-foot syndrome, which were assessed as possibly related to BP1001 and counted as a dose-limiting toxicity. We noted no other dose-limiting toxicities, and a maximum tolerated dose was not identified. The highest tested dose of BP1001 was 90 mg/m². The most common grade 3-4 adverse events were cardiopulmonary disorders (25 [64%] of 39 patients), and fever (including neutropenic fever) and infections (17 [44%] patients). Grade 5 adverse events were cardiopulmonary disorders (two [5%] of 39 patients), fever (including neutropenic fever) and infections (two [5%] of 39 patients), and multi-organ failure (one [3%] of 39 patients). Nine (33%) of 27 patients who had peripheral blood blasts at the start of therapy had a reduction of 50% or more in peripheral blood blasts while receiving BP1001 montherapy. Three (10%) of 29 patients who had bone marrow blasts at the start of therapy had a reduction in bone marrow blasts of 50% or more while receiving BP1001 monotherapy. Per investigator's assessment, seven (22%) of 32 patients benefited from BP1001 monotherapy and had extended cycles of treatment. Of seven patients receiving BP1001 plus low-dose cytarabine combination therapy, two had complete remission, one had complete remission with incomplete haematological recovery, and two had stable disease with no dose-limiting toxicity; one patient died and one withdrew, both because of disease progression. There were eight deaths; none were treatment related.

INTERPRETATION:

BP1001 is well tolerated, with early evidence of anti-leukaemic activity in combination with low-dose cytarabine. To further explore this anti-leukaemic activity, the efficacy of BP1001 plus low-dose cytarabine combination is being investigated in an ongoing phase 2 study in patients with previously untreated acute myeloid leukaemia who are ineligible for intensive induction therapy.

FUNDING:

Bio-Path Holdings Inc.

01 Feb 2008·Journal of biomolecular screening

Development of Binding Assays for the SH2 Domain of Grb7 and Grb2 Using Fluorescence Polarization

Article

Author: Wang-Qing Liu ; Huixiong Chen ; Jean-Philippe Luzy ; Christiane Garbay ; Anne-Françoise Burnol ; Michel Vidal ; Brunilde Gril ; Dominique Perdereau

Adaptor proteins Grb7 and Grb2 have been implicated as being 2 potential therapeutic targets in several human cancers, especially those that overexpress ErbB2. These 2 proteins contain both a SH2 domain (Src homology 2) that binds to phosphorylated tyrosine residues contained within ErbB2 and other specific protein targets. Two assays based on enzyme-linked immunosorbent assay and fluorescence polarization methods have been developed and validated to find and rank inhibitors for both proteins binding to the pY(1139). Fluorescence polarization assays allowed the authors to determine quickly and reproducibly affinities of peptides from low nanomolar to high micromolar range and to compare them directly for Grb7 and Grb2. As a result, the assays have identified a known peptidomimetic Grb2 SH2 inhibitor (mAZ-pTyr-(alphaMe)pTyr-Asn-NH(2)) that exhibits the most potent affinity for the Grb7 SH2 domain described to date.

News (Medical) associated with Prexigebersen

10 Jan 2025

·www.globenewswire.com

Bio-Path Holdings Provides 2025 Clinical and Operational Update

Advancing Multiple Programs in Areas of Significant Unmet Medical Need Several Milestones Across Clinical Development Pipeline Expected in 2025 HOUSTON, Jan. 10, 2025 (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 and obesity drugs, today provides a clinical development and operational update for 2025. “The important work we conducted throughout 2024 has led us into what we believe is an exciting 2025 as we build off positive data generated in oncology and the addition of a new application for BP1001-A in the treatment of obesity for Type 2 Diabetes. This new application compels us to advance these studies as quickly as possible and to file for regulatory designations that could accelerate our path to approval,” said Peter H. Nielsen, President and Chief Executive Officer of Bio-Path. “There is no greater challenge than the battle against cancer, and developing effective new medicines for patients suffering with few treatment options is what drives us every day. The addition of development of a potential treatment for obesity in Type 2 Diabetes patients follows this pathway as these patients need treatment beyond current weight loss drugs to support needed therapy for reducing glucose levels, which has positive impact across a number of different health-related conditions. The substantial progress we have made gives us further confidence that our DNAbilize® platform is ushering in a new path of DNA-powered medicines that can make a difference in the lives of these patients.” Clinical Program Overview Bio-Path’s clinical development program consists of one Phase 2 clinical trial, two Phase 1 or 1/1b clinical trials, and two preclinical programs. Bio-Path has developed a molecular biomarker package for its Phase 2 clinical trial in acute myeloid leukemia (AML) that was developed to identify patients that potentially have a higher propensity to respond to prexigebersen treatment. Bio-Path expects to utilize the biomarker package to accompany prexigebersen treatment in 2025 and expects to evaluate prexigebersen for the treatment of obesity. In addition, BP1001-A is in preclinical development for treatment of obesity in Type 2 Diabetes patients, which may be submitted to the U.S. Food and Drug Administration (FDA) later in the year in an Investigational New Drug (IND) application. Development of Molecular Biomarkers – Bio-Path has developed a molecular biomarker package to accompany prexigebersen treatment, the goal of which is to identify patients with a genetic profile more likely to respond to treatment thereby improving probability of success for this program. The emerging role of biomarkers has been enhancing cancer development over the past decade and has become a more common companion to many cancer development programs. Bio-Path expects to utilize the prexigebersen biomarkers in 2025 in the Phase 2 AML clinical trial and to develop additional molecular biomarker packages to accompany its new programs. Prexigebersen Phase 2 Clinical Trial – Bio-Path’s Phase 2 clinical trial for the treatment of AML is comprised of three cohorts of patients and treatments, each separately approvable by the FDA as a new indication. The first two cohorts are treating patients with the triple combination of prexigebersen, decitabine and venetoclax. The first cohort includes untreated AML patients, and the second cohort includes relapsed/refractory AML patients. Finally, the third cohort is treating relapsed/refractory AML patients who are venetoclax-resistant or intolerant with the two-drug combination of prexigebersen and decitabine. Outcomes for these older patients who are unable to receive intensive chemotherapy due to the challenging side effect profile, remain suboptimal with a median survival of only 5 to 10 months. Bio-Path also expects to utilize an advisory panel of AML experts to assist in the design of the final clinical development plans through potential FDA approval. Other significant milestones expected during 2025 include the completion of Cohort 2 and an interim analysis for Cohort 3. Phase 1/1b Clinical Trial in BP1001-A in Advanced Solid Tumors – A Phase 1/1b clinical trial of BP1001-A in patients with advanced or recurrent solid tumors, including ovarian and uterine, pancreatic and breast cancer, is ongoing. BP1001-A is a modified product candidate that incorporates the same drug substance as prexigebersen but has a slightly modified formulation designed to enhance nanoparticle properties. The Phase 1 study has advanced to the second, higher dose level and the first patient in the second dose cohort continued experiencing a positive response which may signal that this analog of prexigebersen has potential as a new treatment for advanced solid tumors. The patient continues to be doing well after ten months on study after failing extensive chemotherapy and surgical treatment for gynecologic cancer, demonstrating a 15% reduction in her primary tumor through nine cycles of treatment. Moreover, it appears that these positive outcomes may have contributed to allowing her to continue with rigorous exercise and improved quality of life. Completion of the second and third dosing cohorts are expected in 2025. The Phase 1b portion of the study is expected to commence after successful completion of the three BP1001-A monotherapy dose level cohorts and is intended to assess the safety and efficacy of BP1001-A in combination with paclitaxel in patients with recurrent ovarian or endometrial tumors. Phase 1b studies are also expected to be initiated in combination with gemcitabine in Stage 4 pancreatic cancer and combination therapy in breast cancer. Phase 1/1b Clinical Trial in BP1002 in Relapsed/Refractory AML – A Phase 1/1b clinical trial for BP1002 to treat relapsed/refractory AML patients, including venetoclax-resistant patients, is ongoing. BP1002 targets the protein Bcl-2, which is responsible for driving cell survival in up to 60% of all cancers. Venetoclax treats AML patients by blocking the activity of the Bcl-2 protein in AML patients. However, over time patients become resistant to venetoclax. BP1002 treats the Bcl-2 target by blocking the cell’s ability to produce Bcl-2 and could provide benefit for these venetoclax resistant patients. AML patients that fail frontline venetoclax-based therapy have very poor prognosis with median overall survival of less than three months. The first dose cohort consisted of a starting dose of 20 mg/m2, the second dose cohort of 40 mg/m2 and there were no dose limiting toxicities. The third dosing cohort of 60 mg/m2 is open and enrollment closed faster than expected which Bio-Path believes reflects the need for additional treatment options. Prexigebersen as Potential Treatment for Obesity in Type 2 Diabetes Patients – BP1001-A downregulates Grb2 expression to increase insulin sensitivity and helps lower blood glucose level in Type 2 diabetes patients. Scientific evidence suggests that by downregulating Grb2 expression, BP1001-A could help lower blood glucose levels by affecting insulin signaling. Bio-Path conducted preclinical studies that confirmed the effectiveness of BP1001-A in affecting insulin signaling and its potential efficacy as a therapeutic treatment for obese patients who have Type 2 diabetes. In 2025, Bio-Path expects to complete preclinical testing and to file an IND. Intellectual Property Protection Bio-Path’s composition of matter patents are designed to protect encroachment from third parties on its proprietary products. These composition patents allow the Company to apply its core technology to new protein targets and receive new 20-year patents. Bio-Path’s patent portfolio is as follows: Composition and methods of use patents issued cover DNAbilize technology, solely owned by Bio-Path.Seven patents issued in the U.S. with one additional application allowed; 61 foreign patents issued across 24 countries; five additional foreign patent applications allowed; three applications pending in the U.S. along with more than 30 applications pending in foreign jurisdictions. 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.212-362-1200will@sternir.com Doug Morris Investor Relations Bio-Path Holdings, Inc. 832-742-1369

Phase 2Phase 1

19 Dec 2024

·www.globenewswire.com

Bio-Path Holdings Announces Preclinical Testing of BP1001-A as Potential Treatment for Obesity in Type 2 Diabetes Patients Enhances Insulin Sensitivity

Preclinical Studies Confirmed BP1001-A Mechanism of Action and Therapeutic Potential in Obesity and Type 2 DiabetesHOUSTON, Dec. 19, 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 reported that results from preclinical studies of BP1001-A for obesity demonstrated enhanced insulin sensitivity, confirming BP1001-A as a potential treatment for obesity and related metabolic diseases in Type 2 diabetes patients. BP1001-A downregulates growth factor receptor-bound protein 2 (Grb2) expression to increase insulin sensitivity and helps lower blood glucose level in Type 2 diabetes patients. Scientific evidence suggests that by downregulating Grb2 expression, BP1001-A could help lower blood glucose level by affecting insulin signaling. Bio-Path conducted preclinical studies that confirmed the effectiveness of BP1001-A in affecting insulin signaling and its potential efficacy as a therapeutic treatment for obese patients who have Type 2 diabetes. The study results showed: BP1001-A reduced Grb2 protein expression in myoblast cellsBP1001-A increased the levels of phosphorylated AKT and phosphorylated FOXO-1 in myoblast and hepatoma cells in the presence of insulin These initial data confirmed that by downregulating Grb2 expression, BP1001-A could enhance insulin-induced metabolic events by affecting the insulin/phosphoinositol-3 kinase (PI3K)/AKT pathway and increase insulin sensitivity. “The success of our initial preclinical testing, which supports the mechanism of action and highlights the efficacy of BP1001-A to enhance insulin sensitivity, further validates BP1001-A as a potential treatment for obesity in Type 2 diabetes patients. The failure of leading weight loss medications to induce weight loss in obese patients who have Type 2 diabetes creates a compelling need for an alternative method of lowering blood glucose in obese patients who have Type 2 diabetes,” said Peter H. Nielsen, President and Chief Executive Officer of Bio-Path. “We are excited by the rapid progress we have made advancing BP1001-A as a potential treatment for obesity and related metabolic diseases in Type 2 diabetes patients based on previous BP1001-A preclinical studies as they support our continued and rapid development of this promising program.” Bio-Path has initiated animal studies to confirm the efficacy of BP1001-A as a potential treatment for obesity and related metabolic diseases in Type 2 diabetes patients. If successful, Bio-Path anticipates initiating a first-in-human Phase 1 clinical trial in 2025 to further validate safety, measure pharmacokinetics and establish dosing for potential pivotal 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.212-362-1200will@sternir.com Doug Morris Investor Relations Bio-Path Holdings, Inc. 832-742-1369

Phase 2Clinical Result

11 Dec 2024

·www.globenewswire.com

Bio-Path Holdings Outlines Rationale for Development of BP1001-A as Potential Treatment for Obesity in Type 2 Diabetes Patients

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.212-362-1200will@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

Phase 2Phase 1Oligonucleotide

100 Deals associated with Prexigebersen

External Link

KEGG	Wiki	ATC	Drug Bank
D11165	-	-	-

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Myelodysplastic Syndromes	Phase 2	United States	Bio-Path Holdings, Inc.	01 Sep 2017
Philadelphia chromosome positive adult precursor acute lymphoblastic leukemia	Phase 2	United States	Bio-Path Holdings, Inc.	01 Sep 2017
Philadelphia chromosome positive chronic myelogenous leukemia	Phase 2	United States	Bio-Path Holdings, Inc.	01 Sep 2017
Acute Myeloid Leukemia	Phase 2	United States	Bio-Path Holdings, Inc.	01 May 2016
Endometrioid Carcinoma	Phase 1	United States	Bio-Path Holdings, Inc.	19 Aug 2022
Fallopian Tube Carcinoma	Phase 1	United States	Bio-Path Holdings, Inc.	19 Aug 2022
Ovarian mixed epithelial carcinoma	Phase 1	United States	Bio-Path Holdings, Inc.	19 Aug 2022
Peritoneal Neoplasms	Phase 1	United States	Bio-Path Holdings, Inc.	19 Aug 2022
Relapsed Solid Neoplasm	Phase 1	United States	Bio-Path Holdings, Inc.	19 Aug 2022
Chronic phase chronic myeloid leukemia	Phase 1	United States	Bio-Path Holdings, Inc.	01 Jun 2010

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02781883 (ASCO2024) Manual	Phase 2	Acute Myeloid Leukemia	43	BP1001 + DEC + VEN	nkjraqmqze(uclrfaaiju) = fggrbbfxvr brpsvnjgxx (eidyktjokh ) View more	Positive	24 May 2024
				DEC + VENDECVEN	nkjraqmqze(uclrfaaiju) = juogdymksm brpsvnjgxx (eidyktjokh ) View more
NCT02781883 (ASH 12021 \| ASH 22021) Manual	Phase 2	Acute Myeloid Leukemia	12	Decitabine+Prexigebersen	cyeqgtzipt(cktllkvosa) = swnreiptjc dvqlfhfyou (xzgwzyexgw ) View more	Positive	05 Nov 2021
				Decitabine+Venetoclax+Prexigebersen	vufyocrqgf(vukquaxlpi) = bnesbnlwvw vagkzswzpi (lgdqyujnan ) View more
NCT01159028 (Pubmed \| Lancet Haematol) Manual	Phase 1	Hematologic Neoplasms	36	BP1001	vxlmishruh(rycpegezmx) = The most common grade 3-4 adverse events were cardiopulmonary disorders (25 [64%] of 39 patients), and fever (including neutropenic fever) and infections (17 [44%] patients). Grade 5 adverse events were cardiopulmonary disorders (two [5%] of 39 patients), fever (including neutropenic fever) and infections (two [5%] of 39 patients), and multi-organ failure (one [3%] of 39 patients). dfvdugorzm (hbeidsfapv ) View more	Positive	01 Apr 2018
				BP1001+cytarabine

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