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.

On October 16, 2023 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported that the European Commission (EC) has approved KEYTRUDA, Merck’s anti-PD-1 therapy, as a monotherapy for the adjuvant treatment of adults with non-small cell lung cancer (NSCLC) who are at high risk of recurrence following complete resection and platinum-based chemotherapy (Press release, Merck & Co, OCT 16, 2023, View Source [SID1234636004]).

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This approval by the EC follows the positive recommendation from the Committee for Medicinal Products for Human Use received in September 2023 and was based on results from the Phase 3 KEYNOTE-091 trial. At a median follow up time of 46.7 months, KEYTRUDA demonstrated a clinically meaningful improvement in disease-free survival (DFS) in patients who received adjuvant chemotherapy, reducing the risk of disease recurrence or death by 24% (HR=0.76 [95% CI, 0.64-0.91]). At an earlier prespecified interim analysis, with a median follow-up of 32.4 months, KEYTRUDA demonstrated a statistically significant and clinically meaningful improvement in DFS in the overall population (HR=0.76 [95% CI, 0.63-0.91]; p=0.0014) compared to placebo in patients with NSCLC who are at high risk of recurrence (stage IB [T2a ≥4 centimeters]), II or IIIA by American Joint Committee on Cancer seventh edition (AJCC 7th edition).

"In the unfortunate scenario that non-small cell lung cancer recurs after surgery, most patients have to face limited palliative treatment strategies, underscoring the need to improve treatment outcomes for earlier stages of NSCLC," said Dr. Solange Peters, chair of the medical oncology and thoracic malignancies department, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. "This approval of KEYTRUDA marks the first immunotherapy option approved in the EU for patients with non-small cell lung cancer who are at high risk of disease recurrence following surgery and chemotherapy, regardless of PD-L1 expression."

This approval allows marketing of this KEYTRUDA regimen in all 27 EU member states, as well as Iceland, Liechtenstein, Norway and Northern Ireland.

"Today’s approval demonstrates our continued progress to help more patients living with certain types of lung cancer in Europe, treating them earlier in their disease when it may be the most impactful," said Dr. Gregory Lubiniecki, vice president, global clinical development, Merck Research Laboratories. "We are proud that in Europe, KEYTRUDA now has five approved indications in non-small cell lung cancer, in both earlier and advanced stages of disease."

About KEYNOTE-091

The approval was based on data from KEYNOTE-091, also known as EORTC-1416-LCG/ETOP-8-15 – PEARLS, a randomized, Phase 3 trial (ClinicalTrials.gov, NCT02504372) sponsored by Merck and conducted in collaboration with European Organisation for Research and Treatment of Cancer (EORTC) and the European Thoracic Oncology Platform (ETOP). The study evaluated KEYTRUDA compared to placebo for the adjuvant treatment of patients with NSCLC who are at high risk (stage IB [T2a ≥ 4 centimeters], II or IIIA by AJCC 7th edition) of recurrence following complete resection, regardless of tumor PD-L1 expression status, who may or may not have received adjuvant chemotherapy as recommended by their physician. The dual primary endpoints were DFS in the overall population and in patients whose tumors express PD-L1 (tumor proportion score [TPS] ≥50%). Disease-free survival is calculated as the time from randomization to the date of disease recurrence, occurrence of second primary lung cancer, occurrence of second malignancy or death from any cause, whichever occurs first.

An additional efficacy outcome was overall survival (OS). Overall survival results were not mature, with only 58% of pre-specified OS events in the overall population.

The study randomized 1,177 patients (1:1) to receive either KEYTRUDA (200 mg intravenously [IV] every three weeks [Q3W] for one year or maximum 18 doses; n=590); or placebo (IV Q3W for one year or maximum 18 doses; n=587). The median number of doses was 17 for KEYTRUDA and 18 for placebo.

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 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 recent decades, the overall five-year survival rate for patients diagnosed with lung cancer increased from 11% to 15% on average across EU countries. Improved survival rates are due, in part, to earlier detection and screening, reduction in smoking, advances in diagnostic and surgical procedures, as well as the introduction of new therapies. Early detection and screening 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 in 2021.

On October 16, 2023 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a biotechnology company focused on innovating, developing, and delivering novel polyclonal tumor infiltrating lymphocyte (TIL) therapies for patients with cancer, reported the publication of an abstract reporting clinical data for lifileucel which will be presented at the European Society for Medical Oncology ESMO (Free ESMO Whitepaper) Congress 2023, October 20-24, 2023 in Madrid, Spain (Press release, Iovance Biotherapeutics, OCT 16, 2023, View Source [SID1234636003]).

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The abstract reports outcomes of a subset of 12 patients with advanced mucosal melanoma treated with lifileucel in the pooled consecutive cohorts from the C-144-01 trial. All patients had progressed on or after immune checkpoint inhibitor therapy. Patients with mucosal melanoma, which is rare and difficult to treat, have worse outcomes after anti–PD-1 therapy compared to patients with other melanoma subtypes.

The ORR assessed by an independent review committee (IRC) using RECIST v1.1 was 50% (95% CI: 21%–79%). At median study follow-up of 35.7 months, median duration of response (DOR) was not reached (NR; 95% CI: 12.5 months–NR), median progression free survival (PFS) was NR (95% CI: 1.4 months–NR), and median overall survival (OS) was 19.4 months (95% CI: 7.9 months–NR). Treatment emergent adverse events (TEAEs) were consistent with known safety profiles of lymphodepleting chemotherapy and interleukin-2 (IL-2).

The clinically meaningful and durable activity for lifileucel in the subgroup of patients with the rare and difficult-to-treat mucosal melanoma subtype, as well as in the total population of 153 patients treated in the C-144-01 trial, support the potential benefit of lifileucel as a one-time treatment that is differentiated from other immunotherapies for advanced melanoma.

Additional details will be presented in a mini-oral presentation at ESMO (Free ESMO Whitepaper):

Mini Oral Session – Melanoma and Other Skin Tumours: 1086MO – Lifileucel tumor-infiltrating lymphocyte (TIL) cell therapy in patients (pts) with advanced mucosal melanoma after progression on immune checkpoint inhibitors (ICI): Results from the phase 2 C-144-01 study
Saturday, October 21, 3:15 PM – 3:20PM CEST (9:15 AM – 9:20 AM EDT)