On December 20, 2022 BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a pre-commercial-stage biopharmaceutical company focused on oncology, reported results from the Phase 1/2a study of intratumoral cancer vaccine candidate, AGI-134, designed to evaluate the safety and biological activity of AGI-134 in patients with unresectable metastatic solid tumors (Press release, BioLineRx, DEC 20, 2022, View Source [SID1234625437]).

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The study met its primary endpoint of AGI-134’s safety and tolerability. In this first-in-human trial, a total of 38 patients were treated with AGI-134: 5 patients in part 1, the accelerated dose-escalation part of the study; and 33 patients in part 2, the dose expansion part of the study. Part 1 demonstrated that AGI-134 was safe and well tolerated, with no dose-limiting toxicities reported. The maximum tolerated dose was not reached and the recommended dose for part 2 of the study (RP2D) was determined to be up to 200mg. In the dose expansion part 2 of the study, AGI-134 was generally well-tolerated, with treatment-related adverse events being transient and mostly mild to moderate.

Generation of an immune response and markers of clinical efficacy were assessed as secondary endpoints. Most patients analyzed showed an increase in Alpha-Gal antibodies, indicating increased overall immune activity. Additionally, increases in antigen presenting cells (APCs) were observed in most tissue samples analyzed, and T cell and macrophage tumor infiltration was seen in approximately one-third of evaluable patients’ injected tumors, and in approximately half of evaluable patients’ un-injected lesions. Radiological assessments found that 29 percent of patients in the trial achieved best overall response of stable disease. Seven of the 11 patients who achieved stable disease had previously failed checkpoint-inhibitor therapy.

"In this first-in-human, single-agent trial, we were encouraged with AGI-134’s safety profile and the observed initiation of immune activity in patients," said Philip Serlin, Chief Executive Officer of BioLineRx. "We plan to seek publication of our data at a medical congress in 2023, and in consultation with our scientific advisory board, we will determine the next steps for the program in the first half of next year. We want to thank the patients who participated in this important trial, their caregivers, and our physician collaborators."

The Phase 1/2a clinical trial was a multicenter, open-label study, which recruited a total of 38 patients in the UK, Spain and Israel. The study had two parts: part one was an accelerated dose-escalation study in five patients to determine the maximum tolerated dose and the recommended dose for part 2 of the study; part two was a dose expansion study at the recommended dose in 33 patients, designed to evaluate the safety and tolerability of AGI-134, and to validate AGI-134’s mechanism of action using a wide array of biomarkers. For more information on this Phase 1/2a study, see NCT03593226.

PATIENT CHARACTERISTICS

Total enrollment: 38 patients
Gender: 21 Male, 17 Female
Solid Tumor Cancer Type: Melanoma (21), Colon (5), Breast (4), Squamous Cell (3). Sarcoma (2), Cervical Node (1), Endometrial (1), Synovial (1)
ECOG score: 0 to 1 with life expectancy not less than 3 months
SAFETY

AGI-134 was generally well-tolerated, and adverse events (AEs) were mostly transient, mild to moderate in severity
CLINICAL RESPONSE

Best overall response of stable disease (SD) was observed in 29 percent (11/38) of patients according to RECIST1.1 criteria
7 of the 11 patients who achieved stable disease had failed prior checkpoint inhibitor therapy
IMMUNE RESPONSE BIOMARKERS

Increase in Alpha-Gal antibodies

Most patients analyzed showed an increase in Alpha-Gal antibodies as measured by IgG and IgM titers
Tumor infiltration following treatment with AGI-134

59 percent (10/17) of evaluable patients showed an increase in conventional dendritic cells (CD11c+ HLADR+) within or outside of the tumor
29 percent (5/17) of evaluable patients showed an increase in T helper cells (CD3+CD4+) in injected lesions and 47 percent (8/17) in un-injected lesions,
35 percent (6/17) of evaluable patients showed an increase in Cytotoxic T cells (CD3+CD8+) in injected lesions, and 47 percent (8/17) in un-injected lesions
24 percent (4/17) of evaluable patients showed an increase in macrophages (CD68+) in injected lesions and 47 percent (5/17) in un-injected lesions
About AGI-134

AGI-134 is a synthetic alpha-Gal glycolipid in development for solid tumors that is highly differentiated from other cancer immunotherapies. AGI-134 is designed to label cancer cells with alpha-Gal via intra-tumoral administration, thereby targeting the body’s pre-existing, highly abundant anti-alpha-Gal (anti-Gal) antibodies and redirecting them to treated tumors. Binding of anti-Gal antibodies to the treated tumors results in activation of the complement cascade, which destroys the tumor cells and creates a pro-inflammatory tumor microenvironment that also induces a systemic, specific anti-tumor (vaccine) response to the patient’s own tumor neo-antigens.

AGI-134 has been evaluated in numerous pre-clinical studies. In a mouse melanoma model, treatment with AGI-134 led to regression of established primary tumors and suppression of secondary tumor (metastases) development. Synergy has also been demonstrated in additional pre-clinical studies when combined with an anti-PD-1 immune checkpoint inhibitor, offering the potential to broaden the utility of such immunotherapies, and improve the rate and duration of responses in multiple cancer types. AGI-134 was obtained by BioLineRx through the acquisition of Agalimmune Ltd.

On December 20, 2022 Athenex, Inc., (NASDAQ: ATNX), a global biopharmaceutical company dedicated to the discovery, development, and commercialization of novel therapies for the treatment of cancer and related conditions reported that collaborators at the Quantum Leap Healthcare Collaborative reported today that the Company’s oral paclitaxel plus encequidar in combination with a PD-1 inhibitor and carboplatin has graduated in the triple-negative subgroup of high-risk early-stage breast cancer (Press release, Athenex, DEC 20, 2022, View Source [SID1234625436]). Oral paclitaxel, relative to intravenous paclitaxel, was associated with less neuropathy and was not associated with an increase in febrile neutropenia. Quantum Leap Healthcare Collaborative anticipates presenting these results at upcoming national meetings in Q2 of 2023.

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"We are very pleased that the Oral Paclitaxel combination regimen graduated from this prestigious program which has brought exciting and innovative treatments to neoadjuvant breast cancer patients. This study confirms our finding of less neuropathy for Oral Paclitaxel compared to intravenous paclitaxel in our metastatic breast cancer study. It’s reassuring to see that Oral Paclitaxel regimen was not associated with increased febrile neutropenia relative to the intravenous paclitaxel regimen in a well-conducted U.S. study," said Dr. Johnson Lau, Chief Executive Officer of Athenex. "We will explore different opportunities to maximize the value of Oral Paclitaxel."

Please refer to View Source for more information.

On December 20, 2022 Astellas Pharma Inc. (TSE:4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas"), Seagen Inc. (Nasdaq: SGEN) and Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported the U.S. Food and Drug Administration (FDA) has accepted for Priority Review supplemental Biologics License Applications (sBLAs) for PADCEV (enfortumab vedotin-ejfv) and KEYTRUDA (pembrolizumab) for use of these two agents in combination for the treatment of patients with locally advanced or metastatic urothelial cancer (la/mUC) who are not eligible to receive cisplatin-containing chemotherapy (Press release, Astellas, DEC 20, 2022, View Source [SID1234625434]). The respective applications are intended to expand both labels for PADCEV and KEYTRUDA. The agency set a Prescription Drug User Fee Act (PDUFA) goal date for each application of April 21, 2023

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"We look forward to working closely with the FDA as we seek potential accelerated approval for this combination in the hopes that it can be another treatment option for patients with locally advanced or metastatic urothelial cancer who are not eligible for cisplatin-containing chemotherapy," said Ahsan Arozullah, M.D., M.P.H., Senior Vice President and Head of Development Therapeutic Areas, Astellas.

The combination therapy was granted Breakthrough Therapy designation by the FDA in February 2020. The respective sBLAs are supported by efficacy and safety data from the phase 1b/2 EV-103 trial (NCT03288545, also known as KEYNOTE-869) Dose Escalation/Cohort A and Cohort K. Results from Dose Escalation/Cohort A were published in the Journal of Clinical Oncology.1 Results from Cohort K were presented in a late-breaking session at the 2022 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress.2

"Urothelial cancer, the most common type of bladder cancer, is associated with poor survival in the advanced stage," said Marjorie Green, M.D., Senior Vice President and Head of Late-Stage Development, Seagen. "The investigational results from our clinical development program support the combination of PADCEV and KEYTRUDA as a potential treatment for this patient population."

Please see Important Safety Information at the end of this press release for both drugs, including a warning and precaution for immune-mediated adverse reactions for pembrolizumab and BOXED WARNING for PADCEV (enfortumab vedotin-ejfv) for serious skin reactions.

"Despite advancements in treatment options, approximately half of advanced bladder cancer patients in the U.S. are ineligible for cisplatin-based chemotherapy, and these patients need new options. We are encouraged by the investigational results of the combination of PADCEV and KEYTRUDA for this patient population and are fully committed to work to bring this new approach forward to patients," said Dr. Eliav Barr, Senior Vice President, Head of Global Clinical Development and Chief Medical Officer, Merck Research Laboratories.

Astellas, Seagen and Merck are further investigating enfortumab vedotin plus pembrolizumab in the ongoing phase 3 EV-302 study (NCT04223856, also known as KEYNOTE-A39), evaluating the clinical benefit for the investigational treatment combination in patients with previously untreated advanced urothelial cancer. The trial is intended to serve as the confirmatory trial for the potential accelerated approval in the U.S. and serve as the basis for global registration.

The studies are part of an extensive program evaluating this combination in multiple stages of urothelial cancer, including two phase 3 clinical trials in muscle-invasive bladder cancer in EV-304 (NCT04700124, also known as KEYNOTE-B15) and EV-303 (NCT03924895, also known as KEYNOTE-905).

On December 20, 2022 Abbott (NYSE: ABT) reported that it will present at the 41st Annual J.P. Morgan Healthcare Conference on Tuesday, Jan. 10, 2023 (Press release, Abbott, DEC 20, 2022, View Source [SID1234625435]). Robert B. Ford, chairman and chief executive officer, will present at 11 a.m. Central time.

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A live webcast of the presentation will be accessible through Abbott’s Investor Relations website at www.abbottinvestor.com. An archived edition of the presentation will be available later that day.

On December 20, 2022 Nykode Therapeutics ASA (OSE: NYKD), a clinical-stage biopharmaceutical company dedicated to the discovery and development of novel immunotherapies, reported an expanded clinical development plan for VB10.16, the Company’s wholly-owned cancer vaccine, for the treatment of HPV16-positive cancers with high unmet need (Press release, Nykode Therapeutics, DEC 20, 2022, View Source [SID1234625430]). Nykode Management will host a webcast today, December 20, 2022, to discuss the development plan at 11 a.m. CET (in Norwegian) and 4 p.m. CET/10 a.m. ET (in English).

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VB10.16 is an off-the-shelf therapeutic cancer vaccine specifically designed to treat HPV16-induced malignancies. The drug candidate has reported interim data from VB-C-02, a Phase 2 trial in heavily pre-treated cervical cancer patients. The analysis demonstrated a favorable safety profile, with responses observed in both PD-L1 positive and negative patients (ORR 27% and 17%, respectively). The vaccine-induced significant HPV16-specific T cell responses that were associated with clinical responses.

"Today we announce our expanded VB10.16 development plan underlining our confidence in the product candidate’s potential to treat a broad group of HPV-related cancer patients with significant unmet need. These indications constitute a large potential market opportunity for Nykode. Our potential registrational trial strategy disclosed today in advanced cervical cancer could provide a fast path to making VB10.16 available to patients. I am excited by our ambitious VB10.16 development plans and our recently signed agreements supporting the development. We remain committed to taking full advantage of the potential of VB10.16 and Nykode’s technology platform," said Michael Engsig, Chief Executive Officer of Nykode Therapeutics.

Klaus Edvardsen, Chief Development Officer of Nykode Therapeutics, stated: "The interim results from our C-02 Phase 2 trial show the ability of VB10.16 to improve clinical outcomes in heavily pretreated patients with advanced cervical cancer. Our next trial in advanced cervical cancer will focus on patients who failed first line treatment including checkpoint inhibitor treatment. In this patient group with limited treatment options and a significant unmet need, we aim for a potential registrational trial."

Expanded VB10.16 Clinical Development Plan

Cervical Cancer
Nykode is planning to conduct a single arm trial, VB-C-04, with potential registrational intent in 2 nd line immune checkpoint inhibitor refractory advanced cervical cancer patients. The trial will be conducted in the United States and initiated in the fourth quarter of 2023.

Head and Neck Cancer
Nykode is planning to conduct an open-label, dose-finding, single arm Phase 1b/2a trial of VB10.16 in combination with pembrolizumab in patients with first line HPV16-postive, recurrent or metastatic squamous cell head and neck cancer as described in Nykode’s announcement on December 6, 2022. The trial, VB-C-03, will evaluate the overall response rate, safety, tolerability, and antigen specific immune response of the combination therapies. Nykode expects to enroll patients in Europe during the first half of 2023.

Basket Trial
Nykode expects to collaborate on an investigator-initiated basket trial to evaluate VB10.16 in combination with a PD-L1 inhibitor in patients diagnosed with HPV16-positive anal, penile, vaginal and/or vulvar cancer who are no longer eligible for curative treatments. The trial is expected to enroll patients with both PD-L1 positive and PD-L1 negative tumors. Nykode will continue to study VB10.16 in patients with PD-L1 negative tumors to investigate VB10.16’s potential for a dedicated trial in such a patient population.

Webcast
Investors and analysts are invited to join a webcast presentation of the VB10.16 development plan conducted by Michael Engsig, Chief Executive Officer, and Klaus Edvardsen, Chief Development Officer, today, December 20, 2022 at:

11 a.m. CET / 5 a.m. ET which will be conducted in Norwegian
4 p.m. CET / 10 a.m. ET which will be conducted in English

The slide presentation and live and archived webcast can be accessed in the Investors section of the Company’s website at View Source

41st Annual J.P. Morgan Healthcare Conference

Nykode Management will present at the 41st Annual J.P. Morgan Healthcare Conference, taking place January 9-12, 2023, in San Francisco, California.

About VB10.16

VB10.16 is a potentially first-in-class off-the-shelf therapeutic cancer vaccine candidate in development for the treatment of human papillomavirus type 16 (HPV16)-positive cancers. The cancer vaccine is designed based on Nykode’s Vaccibody technology platform of targeting antigens to antigen presenting cells. VB10.16 has reported positive interim data from a Phase 2 trial in heavily pre-treated cervical cancer patients (NCT04405349). The analysis demonstrated a favorable safety profile, with responses observed in both PD-L1 positive and negative patients (ORR 27% and 17%, respectively). The vaccine-induced significant HPV16-specific T cell responses were associated with
clinical responses. The candidate has also demonstrated favorable clinical data in a Phase 1/2a study in pre-cancerous HPV16-induced high grade cervical intraepithelial neoplasia (HSIL; CIN 2/3) demonstrating a statistically significant correlation of immune responses and clinical responses.