On April 2, 2024 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, reported a clinical development and operational update for 2024 (Press release, Bio-Path Holdings, APR 2, 2024, View Source [SID1234641691]).

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"The new year is off to a strong start as we build off positive data generated in 2023 that compel 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 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 and three Phase 1 or 1/1b clinical trials. Bio-Path is developing a molecular biomarker package to accompany prexigebersen treatment and expects to evaluate prexigebersen for the treatment of obesity. In addition, one further drug candidate is in the final stages of preclinical development, 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 is developing 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 develop molecular biomarker packages to accompany its new programs.

Prexigebersen Phase 2 Clinical Trial – Bio-Path’s Phase 2 clinical trial is treating Acute Myeloid Leukemia (AML) patients. This trial is comprised of three separate cohorts of patients and treatments, each separately approvable by the FDA as a new drug 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. Based on positive interim data for safety and efficacy, the Company plans to pursue FDA Fast Track designation for the accelerated approval of prexigebersen for the treatment of fragile AML patients who are unable to tolerate intensive chemotherapy and thus experience very poor clinical outcomes. 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.

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. 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 opened 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. The drug venetoclax treats AML patients by

blocking the activity of the Bcl-2 protein in AML patients. However, patients become resistant to venetoclax. BP1002 treats the Bcl-2 target by blocking the cell’s ability to produce Bcl-2, and could have the potential to eliminate the need for venetoclax. 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, and there were no dose limiting toxicities. Enrollment is now open for patients for the second dose cohort of 40 mg/m2.

Phase 1 Clinical Trial in BP1002 in Refractory/Relapsed Lymphoma and Chronic Lymphocytic Leukemia (CLL) – A Phase 1 clinical trial to evaluate the ability of BP1002 to treat refractory/relapsed lymphoma and refractory/relapsed chronic lymphocytic leukemia (CLL) patients is currently ongoing. The Phase 1 clinical trial is being conducted at the Georgia Cancer Center while two additional clinical trial sites are currently being activated for inclusion in the study, The University of Texas Southwestern and New York Medical College. In January 2024, Bio-Path announced successful completion of the first dose cohort in the Phase 1 clinical trial. A total of six evaluable patients are scheduled to be treated over two dose levels with BP1002 monotherapy in a standard 3+3 design, unless there is a dose limiting toxicity which would require an additional three patients to be tested. There were no dose limiting toxicities in the first dose cohort (20 mg/m2). Enrollment is now open for patients for the second BP1002 dose cohort of 40 mg/m2.

Preclinical Work for BP1003 – The Company continues to advance its drug candidate, BP1003, for the treatment of advanced solid tumors, including pancreatic cancer. BP1003 is an antisense RNAi nanoparticle targeting the STAT3 protein. Plans are to conduct a Phase 1 study of BP1003 in patients with refractory, metastatic solid tumors (pancreatic, non-small cell lung cancer).

Prexigebersen as Potential Treatment for Obesity and Obesity-related Cancers – The RNAi target of prexigebersen is the Grb2 protein, which is involved in activating the RAS/ERK pathway for cell growth. By blocking the cell’s ability to produce Grb2, prexigebersen treatment may limit cell growth. In obesity, two such pathways are related to leptin and insulin. Activation of leptin or insulin receptors can stimulate the RAS/ERK pathway via Grb2i.

Bio-Path believes development of prexigebersen for the treatment for obesity and obesity-related cancers could be accelerated given the large amount of safety data from prexigebersen treatment of leukemia patients and the continued unmet medical need. The Company expects to evaluate prexigebersen for the treatment of obesity as soon as corporate resources are sufficient.

Intellectual Property Protection

Bio-Path’s composition of matter patents protect encroachment from third parties on its proprietary products. This technology is solely owned by Bio-Path. 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.
● Five issued patents in the U.S. and 53 issued patents in foreign jurisdictions, providing protection in 21 countries.

On April 2, 2024 Bicycle Therapeutics plc (NASDAQ: BCYC), a biopharmaceutical company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, reported that management will participate in a fireside chat at the 23rd Annual Needham Virtual Healthcare Conference on April 9, 2024, at 11 a.m. ET (Press release, Bicycle Therapeutics, APR 2, 2024, View Source [SID1234641690]).

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A live webcast of the fireside chat will be accessible from the Investor section of the company’s website at www.bicycletherapeutics.com. A replay of the webcast will be archived and available following the event.

On April 2, 2024 AIM ImmunoTech Inc. (NYSE American: AIM) ("AIM" or the "Company") reported its financial results for the full year 2023 and provided a business update (Press release, AIM ImmunoTech, APR 2, 2024, View Source [SID1234641688]). As previously announced, the Company will host a conference call and webcast today, Tuesday, April 2, 2024, at 8:30 AM ET (details below).

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"AIM reported positive data across many fronts in 2023 and the first quarter of 2024. We intend to build on this momentum throughout the year, as we focus on the execution of our operational, clinical and regulatory initiatives. My goal is to create stockholder value in the near- and long-term as positive data continues to come in," commented AIM Chief Executive Officer Thomas K. Equels.

Recent Highlights

Announced in March 2024 the publication of positive findings from Early Access Program evaluating Ampligen in the treatment of pancreatic cancer in the prestigious journal Clinical Cancer Research
AMP-518 Clinical Study: Phase 2 study evaluating Ampligen as a potential therapeutic for people with the Post-COVID condition of fatigue
Last subject treated and study completed in November 2023
Reported positive topline results in February 2024, offering preliminary evidence that Ampligen may reduce fatigue in subjects with Post-COVID conditions
Bolstered intellectual property estate with November 2023 issuance of key U.S. patent for Ampligen in combination with an anti-PD-L1 antibody – such as AstraZeneca’s Imfinzi (durvalumab) – for the treatment of cancer
DURIPANC Clinical Study: Phase 1b/2 clinical trial combining AIM’s Ampligen with Imfinzi for the treatment of pancreatic cancer
Opened for enrollment and enrolled first subject in January 2024 at Erasmus Medical Center ("Erasmus MC")
First subject dosed in February 2024 at Erasmus MC
Expected Upcoming Pipeline Milestones

Q2 2024

Post-COVID Conditions (AMP-518) – Final dataset
Advanced Recurrent Ovarian Cancer – Protocol-planned interim results
2024

Locally Advanced Pancreatic Adenocarcinoma (AMP-270) – First subject dosed
Publications of data in scientific journals
Summary of Financial Highlights for Fiscal Year 2023

As of December 31, 2023, AIM reported cash, cash equivalents and marketable investments of $13.1 million, compared to $34.2 million as of December 31, 2022.
Research and development expenses for the year ended December 31, 2023, were $10.9 million, compared to $7.0 million for the year ended December 31, 2022.
General and administrative expenses for the year ended December 31, 2023, were $21.1 million, compared to $13.1 million for the year ended December 31, 2022.
Please refer to the full 10-K for complete details.

Conference Call and Webcast Details

As previously announced, the Company will host a quarterly conference call and webcast to discuss the operational and financial results today, April 2, 2024, at 8:30 AM ET.

The call will be hosted by members of AIM’s leadership team, Thomas K. Equels, Chief Executive Officer and Christopher McAleer, PhD, Scientific Officer. Interested participants and investors may access the conference call by dialing (877) 407-9219 (domestic) or (201) 689-8852 (international) and referencing the AIM ImmunoTech Conference Call. The webcast will be accessible on the Events page of the Investors section of the Company’s website, aimimmuno.com, and will be archived for 90 days following the live event.

On April 1, 2024 Ipsen (Euronext: IPN; ADR: IPSEY) and Sutro Biopharma (NASDAQ: STRO, "Sutro", "the Company") reported an exclusive global licensing agreement for STRO-003 (Press release, Sutro Biopharma, APR 2, 2024, View Source [SID1234641672]). STRO-003, an antibody-drug conjugate (ADC) in the final stages of pre-clinical development, targets the ROR1 tumor antigen which is known to be overexpressed in many different cancer types including solid tumors and hematological malignancies.1 The agreement gives Ipsen exclusive worldwide rights to develop and commercialize STRO-003 and will be the first ADC candidate joining Ipsen’s expanding portfolio.

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"The potential for ADCs in oncology is well-documented and we are excited by the addition of STRO-003, Ipsen’s first ADC candidate with best-in-class potential." said Mary Jane Hinrichs, SVP and Head of Early Development at Ipsen. "STRO-003 is a next-generation ROR1 ADC, leveraging Sutro’s site-specific technology to generate a highly stable conjugate, coupled with exatecan payloads, that have shown significant potential in solid tumors. This is our focus as we prepare to enter Phase I, harnessing Ipsen’s global expertise in oncology development, while also reinforcing our commitment to bringing new medicines to patients with few treatment options."

"We are excited to partner STRO-003 with Ipsen to help us reach more patients faster while retaining significant downstream participation in a medicine in which we believe," said Jane Chung, President and Chief Operating Officer at Sutro. "Sutro’s research innovation represented in STRO-003 illustrates our leadership in ADC design. We look forward to collaborating with Ipsen’s impressive oncology development team to bring a differentiated ROR1-targeted ADC to patients."

ADCs are comprised of three main components: the antibody, payload and linker. The antibody selectively targets an identified tumor antigen, such as ROR1. Payloads are the pharmaceutically active component to treat the cancer, attached to the antibody via a chemical linker. The linker connects the antibody and the payload and reduces the amount of payload that reaches non-tumor tissue.2

Under the terms of the agreement, Ipsen will assume responsibility for Phase I preparation activities, including submission of the Investigational New Drug (IND) application, and all subsequent clinical-development activities and global commercialization activities. Sutro Biopharma is eligible to receive up to $900m in potential upfront, development, regulatory and commercial milestone payments including approximately $90m in near-term payments, including an equity investment, and tiered royalties on global sales, contingent upon successful development and commercialization.

On April 2, 2024 AstraZeneca and Daiichi Sankyo reported that Biologics License Application (BLA) for datopotamab deruxtecan (Dato-DXd) has been accepted in the US for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior systemic therapy for unresectable or metastatic disease (Press release, AstraZeneca, APR 2, 2024, View Source [SID1234641671]). The Prescription Drug User Fee Act date, the US Food and Drug Administration (FDA) action date for its regulatory decision, is during the first quarter of 2025.

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The BLA is based on results from the pivotal TROPION-Breast01 Phase III trial in which datopotamab deruxtecan demonstrated a statistically significant and clinically meaningful improvement for the dual primary endpoint of progression-free survival (PFS) compared to investigator’s choice of chemotherapy in patients with unresectable or metastatic HR-positive, HER2-negative breast cancer previously treated with endocrine-based therapy and at least one systemic therapy. For the dual primary endpoint of overall survival (OS), interim results numerically favoured datopotamab deruxtecan over chemotherapy but were not mature at the time of data cut-off. The trial is ongoing and OS will be assessed at future analyses.

Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed by AstraZeneca and Daiichi Sankyo.

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "Despite marked progress in the treatment of HR-positive, HER2-negative breast cancer, most patients with advanced disease develop endocrine resistance and face the prospect of one or several lines of chemotherapy. If approved, datopotamab deruxtecan has the potential to provide these patients an efficacious and better tolerated alternative to conventional chemotherapy."

Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said: "The FDA’s acceptance of the BLA brings us closer to providing patients with previously treated HR-positive, HER2-negative breast cancer an alternative option to conventional chemotherapy earlier in the metastatic setting. Following our recently accepted application for advanced nonsquamous non-small cell lung cancer in the US, along with additional regulatory reviews underway in China, the EU, Japan and other regions, we are working swiftly to bring datopotamab deruxtecan as a potential new treatment option to patients around the world."

Results from TROPION-Breast01 were presented during a Presidential Symposium at the 2023 European Society for Medical Oncology Congress and in an oral presentation at the 2023 San Antonio Breast Cancer Symposium.

The safety profile of datopotamab deruxtecan was consistent with that observed in other ongoing trials with no new safety concerns identified.

An additional BLA for datopotamab deruxtecan based on results from the pivotal TROPION-Lung01 Phase III trial is under review in the US for the treatment of adult patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) who have received prior systemic therapy. Additional regulatory submissions for datopotamab deruxtecan in lung and breast cancer are underway globally.

Notes

HR-positive breast cancer
More than 275,000 breast cancer cases were diagnosed in the US in 2022.1 HR-positive, HER2-negative breast cancer is the most common subtype, accounting for more than 65% of diagnosed cases.2 Breast cancer is considered HR-positive, HER2-negative when tumours test positive for oestrogen and/or progesterone hormone receptors and negative for HER2 (measured as HER2 score of IHC 0, IHC 1+ or IHC 2+/ISH-).2,3 Standard initial treatment for this subtype of breast cancer is endocrine therapy but most patients with advanced disease will develop resistance, underscoring the need for additional options.4,5

TROP2 is a protein broadly expressed in HR-positive, HER2-negative breast cancer and is associated with increased tumour progression and poor survival.6,7

TROPION-Breast01
TROPION-Breast01 is a global, randomised, multicentre, open-label Phase III trial evaluating the efficacy and safety of datopotamab deruxtecan versus investigator’s choice of single-agent chemotherapy (eribulin, capecitabine, vinorelbine or gemcitabine) in patients with unresectable or metastatic HR-positive, HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have progressed on and are not suitable for endocrine therapy per investigator assessment and have received at least one additional systemic therapy for unresectable or metastatic disease.

The dual primary endpoints of TROPION-Breast01 are PFS as assessed by blinded independent central review and OS. Key secondary endpoints include objective response rate, duration of response, investigator-assessed PFS, disease control rate, time to first subsequent therapy and safety. TROPION-Breast01 enrolled more than 700 patients in Africa, Asia, Europe, North America and South America. For more information visit ClinicalTrials.gov.

Datopotamab deruxtecan (Dato-DXd)
Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, datopotamab deruxtecan is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programmes in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanised anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

A comprehensive global clinical development programme is underway with more than 20 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple cancers, including NSCLC, triple-negative breast cancer (TNBC) and HR-positive, HER2-negative breast cancer.