On October 16, 2023 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), a clinical-stage immunotherapeutics company focused on oncology, reported the publication of two abstracts for posters to be presented during the upcoming European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023, taking place from October 20th to 24th at the IFEMA Madrid Conference Center in Madrid, Spain (Press release, Oncolytics Biotech, OCT 16, 2023, View Source [SID1234636009]).

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Abstracts Overview

Abstract / Poster Title Pelareorep (pela) + atezolizumab (atezo) and chemotherapy in first-line (1L) advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) patients – Results from the GOBLET study
Final Publication Number (FPN) 1623P
Poster Date October 23, 2023

Abstract / Poster Title Pelareorep + atezolizumab and chemotherapy in third-line (3L) metastatic colorectal cancer (mCRC) patients – Interim results from the GOBLET study
Final Publication Number (FPN) 619P
Poster Date October 22, 2023

Abstracts Summaries

Abstract 1623P
•The GOBLET Phase 1/2 Simon two-stage basket study was designed to evaluate pelareorep in combination with the PD-L1 inhibitor atezolizumab (atezo) and chemotherapy in patients with different solid tumors. In the first stage of the pancreatic ductal adenocarcinoma (PDAC) cohort, 13 evaluable patients were enrolled (including 92% with metastatic disease, 69% in the liver). Primary objectives were safety and efficacy, measured by Stage 1 success criterion of >3 confirmed responses (PDAC segment). T cell receptor sequencing (TCR-seq) was also performed during the course of treatment.
•Updated data from the study showed that 8 of 13 evaluable patients had a partial response (PR) and 3 had stable disease (SD) for an objective response rate (ORR) of 62% (53% confirmed with two scans) and a clinical benefit rate (CBR) of 85%. As of the data cut-off (January 19, 2023), the median duration of response was 6.0 months, the 6-month progression-free survival (PFS) rate was 72.9%, and the 6-month overall survival (OS) rate was 82.1%. T cell receptor sequencing (TCR-seq) showed an expansion of new and pre-existing T-cell clones. No safety signals were observed. Updated efficacy and TCR-seq results will be presented at ESMO (Free ESMO Whitepaper); final PFS and OS are pending.
•The authors concluded from these data that the combination of pelareorep, atezo and chemotherapy was well-tolerated and that the ORR exceeded the pre-specified success criterion. The authors also noted that these data compare favorably with ORRs from prior first-line PDAC trials.

Abstract 619P
•This abstract evaluated pelareorep combination therapy (pelareorep plus atezo plus chemotherapy, trifluridine/tipiracil) in third-line metastatic colorectal cancer patients with microsatellite stable (MSS) disease. In the first stage of this segment, 15 evaluable patients were enrolled, and the primary

objectives were safety and efficacy, measured by Stage 1 success criterion of >4 patients with SD at week 16. TCR-seq was also performed during the course of the treatment cycle to assess the treatment effect on the T cell repertoire.
•Interim data from the study showed that 5 of 15 patients had SD as their best response, including 4 with SD at week 16, and 10 patients had progressive disease (PD). The CBR, defined as stable disease or better, was 33%. Translational research, including TCR-seq, showed an expansion of new and pre-existing T-cell clones. No safety signals were observed. Updated efficacy (PFS and OS) and TCR-seq results will be presented at ESMO (Free ESMO Whitepaper).
•The authors concluded from these data that the pelareorep combination was well-tolerated and the primary efficacy success criterion was met. The authors believe that protective immune responses were initiated in these patients but that they may have been too immunocompromised or have insufficient time before disease progression to fully benefit from the pelareorep-based immunotherapy.

About GOBLET
The GOBLET (Gastrointestinal tumOrs exploring the treatment comBinations with the oncolytic reovirus peLarEorep and anTi-PD-L1) study is a phase 1/2 multiple indication study in advanced or metastatic gastrointestinal tumors. The study is being conducted at 12 centers in Germany and is being managed by AIO-Studien-gGmbH. The co-primary endpoints of the study are objective response rate (ORR) assessed at week 16 and safety. Key secondary and exploratory endpoints include additional efficacy assessments and evaluation of potential biomarkers (T cell clonality and CEACAM6). The study employs a Simon two-stage design with Stage 1 comprising four treatment groups expected to enroll a total of approximately 55 patients:

1.Pelareorep in combination with atezolizumab, gemcitabine, and nab-paclitaxel in 1st line advanced/metastatic pancreatic cancer patients (n=12);

2.Pelareorep in combination with atezolizumab in 1st line MSI (microsatellite instability)-high metastatic colorectal cancer patients (n=19);

3.Pelareorep in combination with atezolizumab and TAS-102 in 3rd line metastatic colorectal cancer patients (n=14); and

4.Pelareorep in combination with atezolizumab in 2nd line advanced and unresectable anal cancer patients (n=10).

Any cohort showing an ORR above a pre-specified threshold in Stage 1 may be advanced to Stage 2 and enroll additional patients.

About AIO
AIO-Studien-gGmbH (AIO) emerged from the study center of the internal oncology working group within the German Cancer Society (DKG). AIO operates with a non-profit purpose of promoting science and research with a focus on medical oncology. Since its foundation, AIO has become a successful sponsor and study management company and has established itself both nationally and internationally.

On October 16, 2023 NuCana plc (NASDAQ: NCNA) reported a presentation on the ongoing NuTide:701 study of NUC-7738 at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) 2023 that took place October 11-15, 2023 in Boston, Massachusetts (Press release, Nucana BioPharmaceuticals, OCT 16, 2023, View Source [SID1234636008]).

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The NuTide:701 study is in the Phase 2 part investigating NUC-7738 both as a monotherapy in solid tumors and in combination with the anti-PD-1 therapy pembrolizumab in patients with metastatic cutaneous melanoma. All patients had exhausted standard available therapies.

NUC-7738 has been well tolerated both as a monotherapy and in combination with pembrolizumab. Encouraging signs of efficacy, including tumor volume reductions and prolonged time on treatment have been observed in both the monotherapy and combination cohorts.

In the combination cohort of melanoma patients, who had all been previously treated with anti-PD-1 based therapy, numerous patients achieved tumor volume reductions and prolonged time on treatment. One patient who was refractory to the anti-PD-1 plus anti-CTLA-4 therapy combination of nivolumab plus ipilimumab achieved a 50% reduction in tumor volume on NUC-7738 plus pembrolizumab and remains on treatment. Seven of the eleven patients recruited to date remain on treatment.

Patient tumor biopsy data showed that, following treatment with NUC-7738 plus pembrolizumab, expression of PD-1 was reduced and CD8+ T-cells increased, indicating that NUC-7738 may have the ability to potentiate immunotherapy. This finding provides a rationale as to why NUC-7738 plus pembrolizumab may be effective in patients who have progressed on prior immunotherapy.

Hugh S. Griffith, NuCana’s Founder and Chief Executive Officer, said: "We are excited to have reported the first data on NUC-7738 in combination with pembrolizumab in patients with melanoma who had previously received immunotherapy. The patient biopsy data indicate that NUC-7738 may make tumors sensitive to treatment with immunotherapy, including anti-PD-1 agents. We look forward to sharing additional updates as these data continue to mature."

On October 16, 2023 Notable Labs, Inc. ("Notable"), a clinical stage therapeutic platform company developing predictive precision medicines for cancer patients, reported the completion of its merger transaction with VBL Therapeutics ("VBL") (Nasdaq: VBLT) and associated financing (Press release, Notable Labs, OCT 16, 2023, View Source [SID1234636007]). The combined company will focus on the advancement of Notable’s proprietary Predictive Precision Medicines Platform ("PPMP") and therapeutic pipeline focused on cancer patients with high unmet medical needs while completing the development of Volasertib for the treatment of acute myeloid leukemia ("AML") in platform-predicted responders as the flagship program. The ordinary shares of the combined company (renamed Notable Labs, Ltd.) are expected to commence trading on The Nasdaq Capital Market, on a 1-for-35 reverse split basis, under the ticker symbol "NTBL" and a new CUSIP number at the open of market trading on October 17, 2023.

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"This is an important milestone for Notable as we continue to advance the demonstrated value of the PPMP," said Thomas Bock, M.D., Chief Executive Officer of Notable. "The merger will add additional capital to accelerate our continued development of Volasertib for the treatment of AML in PPMP-predicted responding patients. As a publicly traded company, we will continue to evaluate potential additional programs and assets where PPMP is especially suited for risk-reducing and fast-tracking therapeutic development."

With the completion of the merger transaction and $10.3 million in new capital invested prior to the closing by a healthtech-focused investor syndicate, including existing Notable stockholders Builders VC, B Capital Group, Y Combinator, First Round Capital, and Founders Fund, the combined company is now expected to be capitalized through multiple clinical milestones with a cash runway into 2025.

Notable’s PPMP combines multi-dimensional biological assays and machine learning to bio-simulate a patient’s cancer treatment and predict their clinical response to the actual treatment. Four clinical validation studies with recognized academic centers have demonstrated PPMP’s high predictive precision in identifying clinical responders before treatment. PPMP has guided Notable in the selection and development of two clinical-stage therapeutic candidates in platform-predicted responding patients with AML.

Notable’s lead asset derived from PPMP is Volasertib, a highly potent PLK1 inhibitor proven to induce cell cycle arrest and apoptosis in various cancer cells. Phase 2a results for Volasertib in adult AML are expected in 3Q 2024. Notable expects to use PPMP to identify, in-license, and fast-track additional undervalued assets as it builds out its development pipeline.

"I want to thank the entire Notable team for their commitment to our mission to save and improve the lives of cancer patients, as well as our shareholders for their support throughout the years," remarked Prof. Dror Harats, M.D., Chief Executive Officer of VBL Therapeutics.

About the Merger Transaction and Reverse Share Split

The merger agreement was previously announced on February 23, 2023 with unanimous approval by the Board of Directors of each company. Under the terms of the agreement, Notable Labs, Inc. has merged with a wholly-owned Delaware subsidiary of VBL, and stockholders of Notable have received newly issued ordinary shares of VBL. Notable stockholders now own approximately 75% and VBL shareholders own approximately 25% of the combined company, in each case on a fully diluted basis as set forth in the merger agreement. Ordinary shares of the combined company are expected to commence trading on The Nasdaq Capital Market under the ticker symbol "NTBL" at the open of market trading on October 17. The combined company now has approximately 8,936,448 shares outstanding.

On October 16, 2023, prior to the closing of the merger, VBL completed a one-for-35 reverse share split. As a result of the reverse share split, every 35 ordinary shares of VBL, par value NIS 0.01 per share, outstanding immediately prior to the merger were combined and reclassified into one ordinary share, par value NIS 0.35 per share, of VBL. Any fractional shares in connection with the reverse share split were rounded up to the nearest whole share.

JMP Securities, A Citizens Company, served as exclusive financial advisor for Notable and Wiggin and Dana LLP and Meitar Law Offices served as legal counsel to Notable. Chardan served as exclusive financial advisor to VBL Therapeutics and Goodwin Procter LLP and Horn & Co. served as legal counsel to VBL Therapeutics.

Management and Organization

The combined company will operate under the leadership of Notable’s officers, including: Thomas A. Bock, Chief Executive Officer; Scott A. McPherson, Chief Financial Officer; Joseph Wagner, Chief Scientific Officer; and Glenn Michelson, Chief Medical Officer. The board of directors of the combined organization is comprised of seven members, including Thomas Bock, Thomas Dubin, Peter Feinberg, Michele Galen, Thomas Graney and Tuomo Pätsi, and one director from the former VBL board, Michael Rice. The combined company will be headquartered in Foster City, California.

Conference Call and Webcast Information

Notable will host a conference call and webcast tomorrow at 8:30 AM Eastern Time. The call can be accessed by dialing (877) 407-0784 (U.S. and Canada) or (201) 689-8560 (international) and entering passcode 13742176. A link to the live webcast, including the presentation of corporate slides, may be found here. To access a subsequent archived recording, visit the "News & Events" section of the Notable website at www.notablelabs.com.

On October 16, 2023 Nkarta, Inc. (Nasdaq: NKTX), a biopharmaceutical company developing engineered natural killer (NK) cell therapies, reported that it will host a conference call on Tuesday, October 17, 2023 at 8:00 a.m. ET to discuss clinical program updates and organizational cost measures and resource prioritization to support clinical milestones (Press release, Nkarta, OCT 16, 2023, https://ir.nkartatx.com/news-releases/news-release-details/nkarta-host-conference-call-tuesday-october-17-8am-et-discuss [SID1234636006]).

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Conference Call and Webcast
To access the conference call, please register through this link: View Source

A replay will be archived on the Investors section of Nkarta’s website, www.nkartatx.com, for approximately four weeks.

On October 16, 2023 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported that the U.S. Food and Drug Administration (FDA) has approved KEYTRUDA, Merck’s anti-PD-1 therapy, for the treatment of patients with resectable (tumors ≥4 centimeters [cm] or node positive) non-small cell lung cancer (NSCLC) in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery (Press release, Merck & Co, OCT 16, 2023, View Source [SID1234636005]). With this approval, KEYTRUDA has six indications in NSCLC, across both metastatic and earlier stages of NSCLC.

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The approval was based on data from the Phase 3 KEYNOTE-671 trial evaluating KEYTRUDA in combination with chemotherapy as neoadjuvant treatment followed by surgery and continued adjuvant treatment with KEYTRUDA as a single agent, for patients with resectable stage II, IIIA or IIIB (N2) NSCLC per the American Joint Committee on Cancer eighth edition (AJCC 8th edition). In the study, the KEYTRUDA regimen demonstrated statistically significant improvements in event-free survival (EFS) and overall survival (OS), the study’s dual primary endpoints, versus neoadjuvant placebo plus chemotherapy followed by adjuvant placebo alone. The EFS results, which were from the first interim analysis, were published in June 2023 in the New England Journal of Medicine. The detailed OS results will be presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 in Madrid, Spain, on October 20, 2023.

Adverse reactions occurring in patients with resectable NSCLC receiving KEYTRUDA in combination with platinum-containing chemotherapy, given as neoadjuvant treatment and continued as single agent adjuvant treatment, were generally similar to those occurring in patients across tumor types receiving KEYTRUDA in combination with chemotherapy.

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue and can affect more than one body system simultaneously. Immune-mediated adverse reactions can occur at any time during or after treatment with KEYTRUDA, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions. Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of KEYTRUDA (pembrolizumab). Based on the severity of the adverse reaction, KEYTRUDA should be withheld or permanently discontinued and corticosteroids administered if appropriate. KEYTRUDA can also cause severe or life-threatening infusion-related reactions. Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. For more information, see "Selected Important Safety Information" below.

"There remains a need for treatment options to improve outcomes for patients with earlier stages of non-small cell lung cancer," said Dr. Heather Wakelee, principal investigator for KEYNOTE-671, thoracic medical oncologist and professor of medicine at Stanford University and past president of the International Association for the Study of Lung Cancer (IASLC). "This important milestone has the potential to change the current treatment paradigm for resectable non-small cell lung cancer that is greater than four centimeters or has lymph node involvement, by offering an immunotherapy-based regimen that has demonstrated statistically significant improvements in overall survival and event-free survival compared to a placebo and chemotherapy regimen."

"KEYTRUDA continues to change the way non-small cell lung cancer is treated across earlier and metastatic disease regardless of PD-L1 expression," said Dr. Marjorie Green, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories. "This approval marks a pivotal moment for the lung cancer community by providing certain patients with earlier stages of non-small cell lung cancer and healthcare providers with an important new treatment option."

The approval marks the sixth NSCLC indication for KEYTRUDA. The five other indications for KEYTRUDA in NSCLC include:

1) in combination with pemetrexed and platinum chemotherapy for the first-line treatment of patients with metastatic nonsquamous NSCLC, with no EGFR or ALK genomic tumor aberrations;

2) in combination with carboplatin and either paclitaxel or paclitaxel protein-bound for the first-line treatment of patients with metastatic squamous NSCLC;

3) as a single agent for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations and is stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic;

4) as a single agent for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA; and

5) as a single agent for adjuvant treatment following resection and platinum-based chemotherapy for adult patients with stage IB (T2a ≥4 cm), II, or IIIA NSCLC.

Study design

KEYNOTE-671 is a multicenter, randomized, double-blind, placebo-controlled Phase 3 trial (ClinicalTrials.gov, NCT03425643) evaluating KEYTRUDA in combination with neoadjuvant chemotherapy, followed by surgery and continued adjuvant treatment with KEYTRUDA (pembrolizumab) as a single agent, versus placebo plus neoadjuvant chemotherapy, followed by resection and adjuvant placebo, in patients with resectable stage II, IIIA or IIIB (N2) NSCLC per the AJCC eighth edition. Patients were enrolled regardless of tumor PD-L1 expression. Patients with active autoimmune disease that required systemic therapy within two years of treatment, a medical condition that required immunosuppression or a history of interstitial lung disease or pneumonitis that required steroids were ineligible. Randomization was stratified by stage (II vs. III), tumor PD-L1 expression (TPS ≥50% or <50%), histology (squamous vs. nonsquamous), and geographic region (East Asia vs. non-East Asia).

The study enrolled 797 patients who were randomly assigned (1:1) to receive either:

Neoadjuvant KEYTRUDA 200 mg intravenously (IV) every three weeks on Day 1 in combination with cisplatin 75 mg/m2 IV on Day 1 and either pemetrexed 500 mg/m2 IV on Day 1 or gemcitabine 1000 mg/m2 IV on Days 1 and 8 of each 21-day cycle for up to four cycles. Within 4-12 weeks following surgery, KEYTRUDA (200 mg) was administered every three weeks for up to 13 cycles, or;
Neoadjuvant placebo IV every three weeks on Day 1 in combination with cisplatin 75 mg/m2 IV on Day 1 and either pemetrexed 500 mg/m2 IV on Day 1 or gemcitabine 1000 mg/m2 IV on Days 1 and 8 of each 21-day cycle for up to four cycles. Within 4‑12 weeks following surgery, placebo was administered every three weeks for up to 13 cycles.
Treatment with KEYTRUDA or placebo continued until completion of the treatment (17 cycles), disease progression that precluded definitive surgery, disease recurrence in the adjuvant phase, disease progression for those who did not undergo surgery or had incomplete resection and entered the adjuvant phase, or unacceptable toxicity. Assessment of tumor status was performed at baseline, Week 7, and Week 13 in the neoadjuvant phase and within four weeks prior to the start of the adjuvant phase. Following the start of the adjuvant phase, assessment of tumor status was performed every 16 weeks through the end of Year 3, and then every six months thereafter. The trial was not designed to isolate the effect of KEYTRUDA in each phase (neoadjuvant or adjuvant) of treatment.

The main efficacy outcome measures were OS and investigator-assessed EFS. Additional efficacy outcome measures were pathological complete response (pCR) rate and major pathological response (mPR) rate as assessed by blinded independent pathology review (BIPR).

Eighty-one percent of patients in the KEYTRUDA in combination with platinum-containing chemotherapy arm had definitive surgery compared to 76% of patients in the placebo in combination with platinum-containing chemotherapy arm.

About lung cancer

Lung cancer is the leading cause of cancer death worldwide. In 2020 alone, there were more than 2.2 million new cases and approximately 1.8 million deaths from lung cancer globally. Non-small cell lung cancer is the most common type of lung cancer, accounting for about 81% of all cases. In the U.S., the overall five-year survival rate for patients diagnosed with lung cancer is 25%, which is a 21% improvement over the last five years. Improved survival rates are due, in part, to advances in diagnostic and surgical procedures, as well as the introduction of new therapies. However, screening and early detection remain an important unmet need, as 44% of lung cancer cases are not found until they are advanced. Only 5.8% of people in the U.S. who are eligible were screened for lung cancer.