ADXS-503 / Ayala Pharma, OS Therapies - LARVOL DELTA

OS Therapies Announces Issuance of U.S. Patent #12,239,738 Protecting Commercial Manufacturing Market Exclusivity for OST-HER2 in Rare Pediatric Cancer Osteosarcoma and Full Listeria Cancer Immunotherapy Platform into 2040 (BioSpace) - "OS Therapies...today announced the issuance of United States Patent #12,230,738 protecting proprietary commercial manufacturing methods for the Company’s listeria monocytogenes (Lm) cancer immunotherapy platform technology into 2040. The Company is seeking to gain FDA approval for lead asset OST-HER2 in the treatment of pediatric recurrent, fully-resected, lung metastatic osteosarcoma by the end of 2025...Phase 2-stage OST-503 for NSCLC & GBM, Phase 1-stage OST-504 for Prostate cancer, 8 pre-clinical stage immunotherapy candidates are also protected under this patent."

Patent • Glioblastoma • Non Small Cell Lung Cancer • Osteosarcoma • Prostate Cancer

OS Therapies Agrees to Acquire All Listeria Monotygenes-based Immuno-Oncology Programs and IP Assets from Ayala Pharmaceuticals, Adding Phase 2 Lung Cancer and Phase 1 Prostate Cancer Programs to Pipeline (Businesswire) - "OS Therapies, Inc...today announced it has entered into an asset purchase agreement to acquire the listeria monocytogenes-based immuno-oncology programs and related intellectual property (IP) assets from Ayala Pharmaceuticals....The assets being acquired include a Phase 2 lung cancer and Phase1 prostate cancer program, in addition to the gaining direct ownership of the underlying IP related to OS Therapies’ lead asset OST-HER2 for osteosarcoma and other HER2-related indications....OS Therapies anticipates requesting Biologics Licensing Authorization (BLA) for OST-HER2 in osteosarcoma in the second quarter of 2025, and hopes to be granted a BLA and related Priority Review Voucher (PRV) from FDA by the end of 2025."

Commercial • FDA filing • Lung Cancer • Non Small Cell Lung Cancer • Osteosarcoma • Prostate Cancer

Study of ADXS-503 With or Without Pembro in Subjects With Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1/2 | N=24 | Completed | Sponsor: Advaxis, Inc. | Recruiting ➔ Completed | N=74 ➔ 24

Combination therapy • Enrollment change • Metastases • Trial completion • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • ALK • EGFR • PD-L1

[VIRTUAL] A Phase 1 Study of an Off-the-Shelf, Multi-Neoantigen Vector (ADXS-503) Alone and in Combination with Pembrolizumab in Subjects with Metastatic Non-Small Cell Lung Cancer (NSCLC) (SITC 2020) - P1/2 | "The potential effect of A503 to reverse resistance to Pembro is now being studied in an expansion cohort and this combination approach is also being evaluated in the first line treatment setting (Part C). Ethics Approval This study was approved by all Institution’s Ethics Board participating in the trial."

Clinical • Combination therapy • IO biomarker • P1 data • Tumor-specific neoantigens • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8

[VIRTUAL] A phase I study of ADXS-503 alone and in combination with pembrolizumab in subjects with metastatic squamous or non-squamous non-small cell lung cancer (NSCLC). (ASCO 2020) - "ADXS-503 alone has demonstrated a manageable safety profile and immune responses in Part A. The 1x108 CFU was identified as the recommended phase II dose. Dose escalation with A503+ Pembro is ongoing and dose expansion in first line treatment is due to start shortly. Research Funding: ADVAXIS INC"

Clinical • Combination therapy • IO biomarker • P1 data • Acute Kidney Injury • Hypertension • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Nephrology • Non Small Cell Lung Cancer • Oncology • Renal Disease • Solid Tumor • Thoracic Cancer

Immunogenicity and disease control induced by a multineoantigen vaccine (ADXS-503) in patients with metastatic non–small cell lung cancer who have progressed on pembrolizumab. (ASCO 2022) - P1/2 | "Adding A503 to pembro after PD appears to induce innate and adaptive immune responses that may restore or enhance sensitivity to checkpoint inhibitors in pts with clinical benefit."

Clinical • IO biomarker • Tumor-specific neoantigens • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8

A phase 2 study of an off-the-shelf, multi-neoantigen vector (ADXS-503) in patients with metastatic non–small cell lung cancer either progressing on prior pembrolizumab or in the first-line setting. (ASCO 2022) - P1/2 | "The addition of A503 to pembro after disease progression on pembro appears to be well tolerated and induced antigen-specific T-cell responses and durable disease control in 46% of patients in Part B and 67% of patients in Part C. Additional patients are currently being enrolled into both parts of the study to further explore the potential of A503 to restore or enhance sensitivity to checkpoint inhibitors."

Clinical • IO biomarker • P2 data • Tumor-specific neoantigens • Fatigue • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8 • PD-L1

Advaxis Reports Second Quarter Ended April 30, 2022 Financial Results and Provides a Business Update (GlobeNewswire) - P1/2 | N=74 | NCT03847519 | Sponsor: Advaxis, Inc. | "Announced updated clinical and immunogenicity data from the Company’s ongoing Phase 1/2 study evaluating ADXS-503 in combination with KEYTRUDA® at the 2022 ASCO Annual Meeting in Chicago, IL...In part B...Long-term follow up suggests that patients who achieve durable clinical benefit upon addition of ADXS-503 to pembrolizumab include those with PD-L1 expression ≥50% and secondary resistance to KEYTRUDA®; ADXS-503 has pleiotropic effects that may reverse the resistance and/or enhance the activity of KEYTRUDA® in patients with durable clinical benefit, including: the elevation of serum cytokines, the activation of Natural Killer (NK) cells, the proliferation and activation of exhausted CD8+ T-cells and the emergence of memory CD8+ T cells; In Part C, enrolling patients receiving ADXS-503 + KEYTRUDA® in the 1st-line metastatic setting, data continue to show a DCR of 67% (2/3)."

P1/2 data • Oncology

Advaxis to Present Updated Clinical and Immunogenicity Data from Ongoing Phase 1/2 Trial of ADXS-503 in Metastatic Non-Small-Cell Lung Cancer (NSCLC) and Study Design of ADXS-504 Trial in Early Prostate Cancer at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting (GlobeNewswire) - P1/2 | N=74 | ADXS-HOT (NCT03847519) | Sponsor: Advaxis | "Advaxis...announced the publication of updated results from the clinical trial of the lead asset from its ADXS-HOT off-the-shelf, cancer-type specific, immunotherapy program....Overall response rate (ORR) was 14% (2/14) and Disease Control Rate (DCR) was 36% (5/14). Two durable partial responses (PR) sustained for over 9 months and 21 months, respectively."

P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Advaxis to Present Updated Clinical and Immunogenicity Data from Ongoing Phase 1/2 Trial of ADXS-503 in Metastatic Non-Small-Cell Lung Cancer (NSCLC) and Study Design of ADXS-504 Trial in Early Prostate Cancer at the American Society of Clinical Oncology (Yahoo Finance) - P1/2 | N=74 | NCT03847519 | Sponsor: Advaxis, Inc. | "These results from the clinical study ADXS-503-101 evaluating the ADXS-503 construct, which is designed to target certain cancers’ commonly occurring hotspot mutations and other tumor-associated antigens, will be presented at the ASCO Annual Meeting to be held on June 4-7, 2022, along with the trial design of the study of the second construct from the ADXS-HOT program, ADXS-504....Overall response rate (ORR) was 14% (2/14) and Disease Control Rate (DCR) was 36% (5/14); Two durable partial responses (PR) sustained for over 9 months and 21 months, respectively; Three durable cases of stable disease (SD) lasting for over 3, 5 and 14 months, respectively."

Clinical protocol • P1/2 data • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • Thoracic Cancer • Urothelial Cancer

Advaxis to Present at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting (GlobeNewswire) - "Advaxis...announced that it will present data from the Phase 2 study of ADXS-503 in combination with pembrolizumab in patients with metastatic non-small cell lung cancer and data from the Phase 1 study of ADXS-504 in patients with biochemically recurrent prostate cancer at the American Society of Clinical Oncology (ASCO) Annual Meeting being held virtually, on June 3-7, 2022."

P1 data • P2 data • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • Thoracic Cancer • Urothelial Cancer

Advaxis Reports Fiscal Year 2021 Financial Results and Provides a Business Update (GlobeNewswire) - "...'Major milestones for the ADXS-503 trial in the second half of 2022 include updated clinical and immunogenicity data for all patients in Stage 1 in Part B and from up to 10 patients in Part C. Also, initial clinical and immunogenicity data from the ADXS-504 trial in early prostate cancer are expected to be reported in the second half of this year'."

P1 data • P1/2 data • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • Urothelial Cancer

ADXS-503 Plus Pembrolizumab Shows Early Clinical Benefit, Safety in Metastatic NSCLC (OncLive) - P1/2, N=NA; (NCT03847519); "'[Patients with] NSCLC [who are] resistant to PD-1/PD-L1 checkpoint inhibitors [CPI] have limited treatment options. Current treatment guidelines allow for CPI rechallenge, but the ORR seen with this approach is below 10% and a DCR of up to 45%,' Jonathan W. Goldman, MD...stated in a press release. 'Thus, it is encouraging to report that in part B of the study, the documented ORR has now increased to 15.4% and the DCR has reached 46% in the first 13 evaluable patients treated with ADXS-503 as an add-on therapy at progression with pembrolizumab...The durable nature of disease control is also encouraging.'"

P2 data

Advaxis Presents Updated Clinical Data from Ongoing Phase 1/2 Trial of ADXS-503 in NSCLC and Upcoming Milestones (GlobeNewswire) - "Advaxis, Inc...announced updated data from the Company’s ongoing Phase 1/2 study evaluating ADXS-503 in combination with KEYTRUDA®...In Part B of the study, 14 patients have been treated and 13 are evaluable with ADXS-503 as an add on therapy to patients failing pembrolizumab as last therapy with all of them evaluable for safety and efficacy; Combination therapy was well tolerated with no dose-limiting-toxicity; The ORR was 15.4% (2/13) and DCR was 46% (6/13); Enrollment in Part B and Part C of the ongoing study will continue..."

P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

[VIRTUAL] A Phase 1 Study of an Off-the-Shelf, Multi-Neoantigen Vector (ADXS-503) Alone and in Combination with Pembrolizumab in Subjects with Metastatic Non-Small Cell Lung Cancer (NSCLC) (SITC 2020) - P1/2 | "The potential effect of A503 to reverse resistance to Pembro is now being studied in an expansion cohort and this combination approach is also being evaluated in the first line treatment setting (Part C). Ethics Approval This study was approved by all Institution’s Ethics Board participating in the trial."

Clinical • Combination therapy • IO Biomarker • P1 data • Tumor-specific neoantigens • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8

[VIRTUAL] A phase 1 study of an off-the shelf, multi-neoantigen vector (ADXS-503) in subjects with metastatic non-small cell lung cancer (NSCLC) progressing on pembrolizumab as last therapy. (ASCO 2021) - P1/2 | "Clinical Trial Registry Number: NCT03847519 Funding: ADVAXIS INC Background: ADXS-503 (A503) is an off-the-shelf, attenuated Listeria monocytogenes (Lm)-based immunotherapy bioengineered to elicit potent T cell responses against 22 tumor antigens commonly found in NSCLC (i.e., 11 hotspot mutations and 11 tumor-associated antigens, TAAs) . ADXS-503 as an add-on therapy to Pembro at disease progression has been well tolerated and it has induced antigen specific-T cell responses and durable disease control in 44% of pts . Part B cohort is currently enrolling additional pts to further explore the potential reversal of Pembro resistance with ADXS-503."

Clinical • IO biomarker • P1 data • Tumor-specific neoantigens • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8

Advaxis to Present at the Non-Small Cell Lung Cancer Drug Development Summit (GlobeNewswire) - "Advaxis, Inc...announced that Andres Gutierrez, M.D., Executive Vice President and Chief Medical Officer of Advaxis, will present data from Part B of the Company’s Phase 1/2 study of ADXS-503 in combination with Pembrolizumab in patients with metastatic squamous or non-squamous non-small cell lung cancer at the virtual Non-Small Cell Lung Cancer Drug Development Summit on July 15th, 2021."

P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Advaxis and Biosight Announce Entry into Definitive Merger Agreement (GlobeNewswire) - “The combined company plans to advance its pipeline through multiple clinical trials, and anticipates the following milestones over the next 12-18 months: Topline results from the ongoing Phase 2 trial of aspacytarabine, which has completed enrolment, as first-line therapy in AML patients who are unfit for standard chemotherapy; Results from the Phase 2 trial of aspacytarabine in collaboration with the European cooperative group, Groupe Francophone des Myélodysplasies (GFM) in patients with relapsed/refractory AML and higher-risk Myelodysplastic Syndrome (MDS); Initiation in the U.S. of a second, Phase 2 trial of aspacytarabine in patients with relapsed/refractory AML and higher-risk MDS; Results from the ongoing Phase 1/2 trial with ADXS-503 in combination with pembrolizumab in non-small cell lung cancer; and Results from the Phase 1 trial of ADXS-504 in biochemically recurrent prostate cancer.”

Clinical data • New P2 trial • Acute Myelogenous Leukemia • Genito-urinary Cancer • Hematological Malignancies • Lung Cancer • Myelodysplastic Syndrome • Non Small Cell Lung Cancer • Oncology • Prostate Cancer

[VIRTUAL] Evaluation of total PD-1 expression using multi-color flow cytometry in metastatic non-small Cell lung cancer patients treated with multi-neoantigen vector (ADXS-503) alone and in combination of pembrolizumab to assess T-cell & T-cell memory subsets (AACR 2021) - "This novel assay will facilitate the evaluation of total PD-1 expression as a pharmacodynamic biomarker in T-cells when PD-1 blockade is being used. These results also support that combination of ADXS-503 with PD-1 blockade could lead to enhancement of efficacy of anti-tumor immunotherapy."

Clinical • IO biomarker • Tumor-specific neoantigens • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • CD8 • PD-1 • PD-L1

Advaxis Presents Updated Clinical Data from Ongoing Phase 1/2 Trial of ADXS-503 in NSCLC at the American Society of Clinical Oncology (ASCO) 2021 Annual Meeting (GlobeNewswire) - P1/2, N=74; NCT03847519; Sponsor: Advaxis, Inc; "...'These early results, which include a disease control rate of 44% in the first 9 evaluable patients treated with ADXS-503 as an add on therapy at progression with pembrolizumab, are particularly encouraging given the durable nature of disease control in 3 patients,' said Suresh Ramalingam...10 patients have been treated with ADXS-503 as an add on therapy to patients failing pembrolizumab as last therapy with 10 patients evaluable for safety and 9 patients evaluable for efficacy…The Disease Control Rate (DCR) was 44% (4/9). Clinical benefit was durable, with an observed partial response (PR) and stable disease (SD) sustained for over a year, and another observed SD lasting over 6 months. An additional PR was maintained for approximately 4 months. Biomarker data demonstrate that patients who seem to achieve clinical benefit include those with PD-L1 expression 50%, secondary resistance disease to pembrolizumab and...

P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Advaxis Presents Translational Biomarker Data from Ongoing ADXS-503 Phase 1/2 Lung Cancer Trial at the American Associated for Cancer Research (AACR) 2021 Annual Meeting (GlobeNewswire) - P1/2, N=74; NCT03847519; Sponsor: Advaxis; "Advaxis...announced data on the development of a novel flow immunophenotyping assay to accurately evaluate total PD-1 expression as a pharmacodynamic marker during PD-1 blockade, and translational data demonstrating immune responses correlated to observed clinical benefit from the Company’s ongoing Phase 1/2 study evaluating ADXS-503 in combination with KEYTRUDA®, presented as a poster at the American Association for Cancer Research (AACR) Annual Meeting 2021....Preliminary flow cytometry data demonstrated on-mechanism activation of innate and adaptive immune responses to ADXS-503."

Biomarker • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Advaxis to Present at the American Society of Clinical Oncology (ASCO) 2021 Annual Meeting (GlobeNewswire) - "Advaxis...announced that will present data from Part B of the Phase 1 study of ADXS-503 in combination with pembrolizumab at the American Society of Clinical Oncology (ASCO) Annual Meeting being held virtually, on June 4-8, 2021."

P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Immunotherapy Treatments For Non Small Cell Lung Cancer Nsclc (Cute 766) - "A new type of immunotherapy treatment for metastatic non small cell lung cancer (nsclc) is being tested by missak haigentz, jr, md...early results appear promising in this phase 1 2 clinical trial of adxs 503, a new type of cancer therapy which targets hotspot. The integration of radiotherapy with immunotherapy for the treatment of non small cell lung cancer five year survival rates for non small cell lung cancer (nsclc) range from 14% to 49% for stage i to stage iiia disease, and are <5% for stage iiib iv disease."

Advaxis to Present at the American Association for Cancer Research (AACR) 2021 Annual Meeting (GlobeNewswire) - "Advaxis, Inc...and Precision for Medicine...announce that they will present data on a) the development of a novel flow immunophenotyping assay to accurately evaluate total PD-1 expression as a pharmacodynamic biomarker during PD-1 blockade treatment with pembrolizumab and b) the correlation of changes in T cell populations with the clinical activity observed in the ongoing ADXS-503 clinical trial, in a poster presentation at the American Association for Cancer Research (AACR) Annual Meeting 2021, taking place virtually from April 10-15, 2021."

Biomarker • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Advaxis Reports First Quarter Ended January 31, 2021 Financial Results and Provides a Business Update (GlobeNewswire) - "'We are encouraged by the growing body of evidence that suggest ADXS-503 has the potential to synergistically enhance and/or restore sensitivity to checkpoint inhibitors...Based on our encouraging data, we are prioritizing the ongoing and recently expanded ADXS-503 trial in diverse treatment settings for NSCLC....Our strengthened balance sheet leaves us well positioned to continue progress with our off-the-shelf neoantigen immunotherapy ADXS-HOT program, including our planned expansion into prostate cancer with ADXS-504, and we look forward to providing study updates in the coming months.'...Research and development expenses for the first quarter of fiscal year 2021 were $2.6 million, compared with $4.9 million for the first quarter of fiscal year 2020."

Clinical • Commercial • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer