On July 17, 2023 BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a pre-commercial stage biopharmaceutical company pursuing life-changing therapies for certain cancers and rare diseases, reported the initiation of a randomized, investigator-initiated Phase 2 clinical trial in first line metastatic pancreatic cancer based on preliminary data from the single-arm pilot phase (Press release, BioLineRx, JUL 17, 2023, View Source [SID1234633255]). The combination drug trial includes the investigational candidate motixafortide. Sponsored by Columbia University, the amended study will modify a single-arm trial whose original design called for expansion to an additional 30 patients if data from a pilot phase of 10 patients was encouraging (defined as ≥3 patients with partial response by RECIST criteria). The amended randomized study will compare combination treatment with the Company’s CXCR4 inhibitor (motixafortide), a PD-1 inhibitor (cemiplimab), and chemotherapy (gemcitabine, nab-paclitaxel) to chemotherapy alone in a larger number of patients (n= 102).

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A poster of the amended clinical trial design was presented at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, held June 2-6 in Chicago, Illinois (see abstract).

"Metastatic pancreatic cancer is a uniformly fatal disease for which current treatments result in limited benefits," said Tami Rachmilewitz, MD, Chief Medical Officer at BioLineRx. "Unfortunately, newer immunotherapy approaches, while beneficial against other solid tumor types, have had limited efficacy in pancreatic cancer due to immunosuppressive pathways. Combining checkpoint inhibitors, chemotherapy, and a CXCR4 inhibitor has shown promise in earlier preclinical and clinical studies, including an earlier single arm study using motixafortide as the CXCR4 inhibitor (COMBAT/KEYNOTE-202) in patients receiving second line treatment for pancreatic cancer, and we are very encouraged by the results seen in the initial pilot phase of the study in patients receiving first line treatment. We look forward to continuing the clinical research of this treatment regimen in this randomized trial."

"Working with our collaborators, we are excited to be advancing the clinical development of motixafortide in pancreatic cancer and look forward to the presentation of data from the pilot phase of the randomized trial later this year," said Philip Serlin, Chief Executive Officer of BioLineRx. "This is an important area of growth for the company, alongside the potential approval and U.S. commercialization of motixafortide this year in stem cell mobilization for autologous transplantation in multiple myeloma."

Data from the pilot stage of the Phase 2 study is planned for submission to a congress later this year. The primary endpoint of the randomized trial is progression free survival (PFS). Secondary objectives include safety, response rate, disease control rate, duration of clinical benefit and overall survival.

The U.S. Food and Drug Administration has accepted the company’s New Drug Application for motixafortide in stem cell mobilization for autologous transplantation in multiple myeloma and assigned the NDA a PDUFA date of September 9, 2023.

About Pancreatic Cancer
Pancreatic cancer has a low rate of early diagnosis and a poor prognosis. In the United States in 2023, an estimated 64,050 adults will be diagnosed with the disease, which accounts for approximately 3% of all cancers in the U.S. and about 7% of all cancer deaths. Worldwide, an estimated 495,773 people were diagnosed with the disease in 2020. In the U.S., if the cancer is detected at an early stage when surgical removal of the tumor is possible, the 5-year relative survival rate is 44%. About 12% of people are diagnosed at this stage. If the cancer has spread to surrounding tissues or organs, the 5-year relative survival rate is 15%. For the 52% of people who are diagnosed after the cancer has spread to a distant part of the body, the 5-year relative survival rate is 3%.[i] These data highlight the need for the development of new therapeutic options.

About Motixafortide in Cancer Immunotherapy
Motixafortide inhibits CXCR4, a chemokine receptor and a well validated therapeutic target that is over-expressed in many human cancers including pancreatic ductal adenocarcinoma (PDAC). Motixafortide leverages the expression of the CXCR4 receptor on different immune cells and potentiates the immune system against the tumor. Among CXCR4-expressing immune cells, some exhibit anti-tumoral activity, such as effector T cells and some exhibit pro-tumoral activity and support tumor growth. By blocking the CXCR4 receptor, motixafortide was shown in a Phase 2 study in pancreatic cancer patients to enhance anti-tumoral activity and to ameliorate the pro-tumoral activities by modulating the effector/suppressor cell ratio towards a proinflammatory profile.

On July 17, 2023 Bio-Path Holdings, Inc., (NASDAQ:BPTH), a biotechnology company leveraging its proprietary DNAbilize antisense RNAi nanoparticle technology to develop a portfolio of targeted nucleic acid cancer drugs, reported completion of the first dose cohort of the dose escalation portion of its Phase 1/1b clinical trial of BP1001-A (liposomal Grb2) in patients with solid tumors, including ovarian, endometrial, pancreatic and breast cancer (Press release, Bio-Path Holdings, JUL 17, 2023, View Source [SID1234633254]).

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"We are delighted to have completed the first cohort of this first-in-human Phase 1/1b study of BP1001-A as it further demonstrated the drug’s favorable safety profile, which is critical for the treatment of these very vulnerable cancer patients," said Peter Nielsen, President and Chief Executive Officer of Bio-Path Holdings. "Importantly, this achievement enables us to advance to the second cohort of this important study in solid tumor cancers, for which we hope to complete enrollment by year end 2023."

The dose escalation portion of the Phase 1/1b clinical trial is ongoing at more than eight leading cancer centers in the United States, including The University of Texas MD Anderson Cancer Center, The Mary Crowley Cancer Research Center, and Karmanos Cancer Center. Initially, a total of nine evaluable patients are scheduled to be treated with BP1001-A monotherapy in a standard 3+3 design, with a starting dose of 60 mg/m2 and continuing with 90 mg/m2 and 135 mg/m2. The approved treatment cycle is two doses per week over four weeks, resulting in eight doses administered over twenty-eight days. The Phase 1b portion of the study will commence after successful completion of BP1001-A monotherapy cohorts and will assess the safety and efficacy of BP1001-A in combination with paclitaxel in patients with recurrent ovarian or endometrial tumors, and BP1001-A with gemcitabine in patients with metastatic pancreatic tumors.

Three patients were enrolled into the first dose cohort of BP1001-A at 60 mg/m2 at three different centers in the study, including one patient with hepatic lesions (and lung metastases) and two with advanced gynecologic lesions. All three patients had undergone extensive previous chemotherapies and/or surgeries for their disease prior to enrollment in this Phase 1 study. No patient experienced any treatment related adverse events or any adverse events deemed related to the study drug.

About BP1001-A

BP1001-A is a modified drug product with the same drug substance as Bio-Path’s lead drug candidate, prexigebersen, but includes formulation enhancements to produce smaller drug nanoparticles. The goal of this product enhancement is to produce smaller drug nanoparticles that can pass through vasculature pore spaces, thereby enabling release of the drug product into the interior of the tumor to enhance drug effectiveness. In preclinical testing in mice, results clearly demonstrated that the reduced size formulation produced a reduction in tumor burden, evidence that the drug product effectiveness was improved with the smaller drug product nanoparticles.

On July 17, 2023 Adcentrx Therapeutics ("Adcentrx"), a biotechnology company dedicated to revolutionizing Antibody-Drug Conjugate (ADC) therapeutics for cancer and other life-threatening diseases, reported that the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug (IND) application of ADRX-0706 for the treatment of select advanced solid tumors (Press release, Adcentrx Therapeutics, JUL 17, 2023, View Source [SID1234633253]).

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"The FDA’s acceptance of our IND application is an exciting milestone for Adcentrx," said Hui Li, Ph.D., Founder and Chief Executive Officer of Adcentrx. "As our first program to receive FDA clearance, we are one step closer to bringing our novel ADC technology to patients in need across the oncology landscape."

Nectin-4 is an attractive target for ADCs due to its high expression in multiple solid tumors and limited expression in normal tissues. It plays a crucial role in tumor progression and has been associated with poor prognosis and resistance to conventional therapies. By specifically targeting Nectin-4 with ADRX-0706, potent anti-cancer activity can be achieved with a lower toxicity profile, offering a promising alternative over current therapeutic approaches.

"ADRX-0706 demonstrated a remarkable efficacy and safety profile in preclinical studies," added Pia Challita-Eid, Ph.D., Chief Scientific Officer of Adcentrx. "We are thrilled to be progressing our first program into the clinic as we continue to apply our optimized ADC platform on a robust and differentiated product pipeline."

The first-in-human Phase 1a/1b clinical trial of ADRX-0706 will be an open-label, multicenter, non-randomized dose escalation and dose expansion study. The study will enroll patients with select advanced solid tumors. The primary objectives of the study will be to characterize the safety and tolerability and to determine the optimal dose of ADRX-0706. The company expects the first patient to be enrolled in the second half of 2023, with an initial data readout in the middle of 2024.

About ADRX-0706

ADRX-0706 is an ADC product candidate discovered by Adcentrx. The antibody component targets Nectin-4, a cell surface adhesion protein over-expressed in multiple human cancers and associated with poor disease prognosis. The ADC is manufactured using a proprietary conjugation technology and novel tubulin inhibitor payload to generate an ADC with a drug-antibody ratio of eight (DAR 8). ADRX-0706 has demonstrated a favorable pharmacokinetic and safety profile in preclinical models, in addition to demonstrating significant efficacy across a variety of tumor indications.

On July 16, 2023 Antengene Corporation Limited ("Antengene" SEHK: 6996.HK), a leading innovative, commercial-stage global biopharmaceutical company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class therapeutics in hematology and oncology, reported that the Department of Health, the Government of the Hong Kong Special Administrative Region (HKSAR) has approved a New Drug Application (NDA) for XPOVIO (selinexor), applicable in combination with dexamethasone (Xd), for the treatment of adult patients with relapsed and/or refractory multiple myeloma (R/R MM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors (PIs), two immunomodulatory agents (IMiDs), an anti-CD38 monoclonal antibody, and who have demonstrated disease progression on the last therapy (Press release, Antengene, JUL 16, 2023, View Source [SID1234633247]).

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XPOVIO is the world’s first oral selective inhibitor of the nuclear export protein (XPO1), with regulatory approvals in 41 countries and regions including the United States, Israel, the United Kingdom, the European Union (the 27 member countries including France and Italy), Canada, Norway, Iceland, Lichtenstein, South Korea, mainland of China, Taiwan China, Hong Kong China, Singapore, Australia and Northern Ireland. To date, 6 XPOVIO regimens received a total of 27 inclusions into 7 clinical guidelines of major oncology societies in the U.S., the EU, and APAC, including 5 regimens for the treatment of myeloma and 1 regimen for the treatment of lymphoma added to the guidelines of the National Cancer Care Network (NCCN); 4 regimens for the treatment of myeloma and 1 regimen for the treatment of lymphoma added to the guidelines of the Chinese Society of Clinical Oncology (CSCO); 5 regimens for the treatment of myeloma added to the guidelines for the Diagnosis and Management of First Relapsed Multiple Myeloma in China; 4 regimens for the treatment of myeloma added to the guidelines for the Diagnosis and Management of Multiple Myeloma in China; 4 regimens for the treatment of myeloma added to the China Anti-Cancer Association’s Guidelines for the Holistic lntegrative Management of Cancers (CACA); 2 regimens for the treatment of myeloma added to the guidelines of the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper); and 1 regimen for the treatment of myeloma added to the guidelines of the International Myeloma Working Group (IMWG).

"Antengene is very pleased to receive regulatory approval for XPOVIO in Hong Kong. Despite recent advances in the treatment of R/R MM, there remains an unmet need to extend survival for patients with this life-threatening disease and the approval of XPOVIO presents Hong Kong patients with access to a novel therapy in their treatment of R/R MM. We will continue to build out Antengene’s presence across APAC markets and strive to expand the indications of XPOVIO in Hong Kong and the broader APAC region, in efforts to bring renewed hope to more cancer patients." said Thomas Karalis, Antengene’s Corporate Vice President, Head of Asia Pacific Region.

"I am pleased that XPOVIO has become the first and only XPO1 inhibitor approved for the treatment of R/R MM in Hong Kong," said Dr. Jay Mei, Antengene’s Founder, Chairman and CEO. Dr. Mei continued, "the Company’s Named Patient Program (NPP), a growing group of investigator-sponsored studies and ongoing advisory boards have helped us to ready the path for the successful adoption of XPOVIO in Hong Kong. Moving forward, we will establish access to ASEAN markets that have a total population exceeding 600 million. To date, Antengene has successfully submitted NDAs in Macau China, Thailand, Malaysia and Indonesia."

About Multiple Myeloma

Multiple myeloma (MM) is caused by the dysregulated proliferation of plasma cells. It is the second most common hematologic malignancy in many countries. Despite availability of a number of treatments for relapsed patients, MM is prone to relapse and most patients still succumb to their disease. MM is the second most common hematologic malignancy in China, with an estimated about 15,000 to 20,000 new MM patients and 10,300 deaths per year.[1]

About XPOVIO (selinexor)

XPOVIO is the world’s first approved orally-available, selective inhibitor of the nuclear export protein XPO1. It offers a novel mechanism of action, synergistic effects in combination regimens, fast onset of action, and durable responses.

By blocking the nuclear export protein XPO1, XPOVIO can promote the intranuclear accumulation and activation of tumor suppressor proteins and growth regulating proteins, and down-regulate the levels of multiple oncogenic proteins. XPOVIO delivers its antitumor effects through three mechanistic pathways: 1) exerting antitumor effects by inducing the intranuclear accumulation of tumor suppressor proteins; 2) reducing the level of oncogenic proteins in the cytoplasm by inducing the intranuclear accumulation of oncogenic mRNAs; 3) restoring hormone sensitivity by activating the glucocorticoid receptors (GR) pathway. To utilize its unique mechanism of actions, XPOVIO is being evaluated for use in multiple combination regimens in a range of indications. At present, Antengene is conducting 8 clinical studies of XPOVIO in mainland of China for the treatment of relapsed/refractory hematologic malignancies and solid tumors (3 of these studies are being jointly conducted by Antengene and Karyopharm Therapeutics Inc. [Nasdaq:KPTI]).

XPOVIO is approved in South Korea for the following two indications:

In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma (R/R MM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody.
As a monotherapy for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy.
XPOVIO is approved in mainland of China for the following indication:

In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma (R/R MM) who have received prior therapies and whose disease is refractory to at least one proteasome inhibitor, at least one immunomodulatory agent, and an anti-CD38 monoclonal antibody.
XPOVIO is approved in Taiwan China for the following three indications:

In combination with dexamethasone (Xd) for the treatment of adult patients with relapsed or refractory multiple myeloma (R/R MM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors (PIs), at least two immunomodulatory agents (IMiDs), and an anti-CD38 monoclonal antibody.
In combination with bortezomib and dexamethasone (XVd) for the treatment of adult patients with MM who have received at least on prior therapy.
As a monotherapy for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) , not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy.
XPOVIO is approved in Hong Kong China, for the following indication:

In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma (R/R MM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors (PIs), two immunomodulatory agents (IMiDs), an anti-CD38 monoclonal antibody (mAb), and who have demonstrated disease progression on the last therapy.
XPOVIO is approved in Australia for the following two indications:

In combination with bortezomib and dexamethasone (XVd) for the treatment of adult patients with multiple myeloma (MM) who have received at least one prior therapy.
In combination with dexamethasone (Xd) for the treatment of adult patients with relapsed or refractory multiple myeloma (R/R MM) who have received at least three prior therapies and whose disease is refractory to at least one proteasome inhibitor (PI), at least one immunomodulatory agent (IMiD), and an anti-CD38 monoclonal antibody (mAb).
XPOVIO is approved in Singapore for the following three indications:

In combination with bortezomib and dexamethasone for treatment of adult patients with multiple myeloma (MM) who have received at least one prior therapy.
In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma (R/R MM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody.
As a monotherapy for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy who are not eligible for haematopoietic cell transplant.

On July 15, 2023 Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel therapies for rare and ultra-rare diseases, reported the grant of 36,300 restricted stock units of the company’s common stock to 21 newly hired non-executive officers of the company (Press release, Ultragenyx Pharmaceutical, JUL 15, 2023, View Source [SID1234633244]). The awards were approved by the compensation committee of the company’s board of directors and granted under the Ultragenyx Employment Inducement Plan, with a grant date of July 16, 2023, as an inducement material to the new employees entering into employment with Ultragenyx in accordance with Nasdaq Listing Rule 5635(c)(4).

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The restricted stock units vest over four years, with 25% of the underlying shares vesting on each anniversary of the grant date, subject to the employee being continuously employed by the company as of such vesting dates.