Purple Biotech to Present New Data On its Oncology Drug NT219 at AACR 2024

On March 28, 2024 Purple Biotech Ltd. ("Purple Biotech" or "the Company") (NASDAQ/TASE: PPBT), a clinical-stage company developing first-in-class therapies that harness the power of the tumor microenvironment to overcome tumor immune evasion and drug resistance, reported it will present data for its oncology candidate NT219, a first-in-class small molecule, dual-inhibitor of IRS 1/2 and STAT3, in two poster presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting which takes place April 5-11, 2024, in San Diego, California (Press release, Purple Biotech, MAR 28, 2024, View Source [SID1234641575]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The growing body of clinical, biomarker, and preclinical data for NT219 demonstrate its potential not only in the lead indication of recurrent/metastatic squamous cell carcinoma of the head and neck, but also in other solid-tumor cancers. These publications at AACR (Free AACR Whitepaper) 2024 are a result of the progress made last year both in clinical and preclinical work bringing out NT219’s attributes," stated Gil Efron, Chief Executive Officer of Purple Biotech. "We look forward to leveraging these data as we move forward with the clinical evaluation of NT219."

Dr Hadas Reuveni, VP Research and Development at Purple Biotech, added, "At AACR (Free AACR Whitepaper) 2024 we will present new data related to NT219. We show for the first time the potential of NT219 to effectively suppress cancer stem cells (CSC), a critical cell population for tumor propagation, characterized by self-renewal and multipotency, and known to promote resistance and tumor recurrence. In addition, synergistic effect of NT219 and mKRAS inhibitors is demonstrated, suggesting a novel mechanism to combat resistance to both KRASG12C and KRAS KRASG12D inhibitors in lung cancer and pancreatic cancers, respectively, both aggressive diseases with unmet medical need. In another presentation, we show the results of translational research in our Phase 1 study, suggesting activated IGF1R and STAT3 as potential biomarkers for the treatment with NT219. We will further evaluate these biomarkers in the next study."

Poster Details:

Title: NT219, a dual inhibitor of IRS1/2 and STAT3, suppresses cancer stem cell mediated resistance to KRASG12C and KRASG12D inhibitors in solid tumors

Session Category: Experimental and Molecular Therapeutics

Session Title: Drug Resistance 2: Ras GTPase

Session Date and Time: Monday Apr 8, 2024, 9:00 AM – 12:30 PM PST

Published Abstract Number: 1939

Title: Early activity and biomarker evaluation of NT219 in combination with cetuximab in a Phase 1/2 study of recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN)

Session Category: Clinical Research

Session Title: Predictive Biomarkers 4

Session Date and Time: Tuesday Apr 9, 2024, 9:00 AM – 12:30 PM PST

Published Abstract Number: 5181

The abstracts are available on the AACR (Free AACR Whitepaper) Online Program Planner and were published in the online-only Proceedings supplement to the AACR (Free AACR Whitepaper) journal Cancer Research. The presented posters will be available on the Publications section of Purple Biotech’s website, following their presentations at the conference.

Omega Therapeutics Reports Fourth Quarter and Full Year 2023 Financial Results and Provides Strategic Update

On March 28, 2024 Omega Therapeutics, Inc. (Nasdaq: OMGA) ("Omega"), a clinical-stage biotechnology company pioneering the development of a new class of programmable epigenomic mRNA medicines, reported financial results for the fourth quarter and full year ended December 31, 2023, and a strategic prioritization initiative to focus resources on near-term milestones to support long-term shareholder value (Press release, Omega Therapeutics, MAR 28, 2024, View Source [SID1234641574]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"2023 was an important year for Omega where we executed to plan and demonstrated clinical validation of an epigenomic controller to regulate c-MYC in humans for the first time. These proof-of-platform clinical data, coupled with our research collaboration with Novo Nordisk in obesity, support the ability of the OMEGA platform to potentially address epigenomic regulation of almost all human genes across broad therapeutic areas including cancer, cardiometabolic conditions and liver regeneration," said Mahesh Karande, President and Chief Executive Officer of Omega Therapeutics. "Initial clinical data from our ongoing Phase 1/2 MYCHELANGELO I trial of OTX-2002 demonstrated controlled modulation of MYC expression levels, one of the most challenging gene targets in oncology, and an encouraging disease control rate and stable disease in heavily pre-treated, late-stage HCC patients. We are within what we believe is a clinically meaningful dose range and, as we continue to see a promising safety profile for OTX-2002, have recently opened enrollment of Cohort 5. We look forward to sharing additional updates from this program throughout 2024."

"Today we also announced a strategic prioritization, implemented to ensure we have sufficient resources to advance our lead program and maximize near- and long-term value creation from our platform. As part of this initiative, we are taking difficult but necessary actions to streamline our team and optimize our R&D efforts and cost structure to extend our cash runway into the first quarter of 2025. These changes will unfortunately affect a number of our colleagues, and we are grateful for their dedication and contributions to our mission," continued Mr. Karande. "As we sharpen our focus, we look forward to the opportunities ahead to generate meaningful clinical data for OTX-2002, continue to demonstrate the broad potential of our platform, and establish additional partnerships. We remain steadfast in our mission to pioneer a new class of programmable epigenomic mRNA medicines to transform the treatment of a broad range of diseases."

Recent Highlights and Key Anticipated Milestones

Development Pipeline and Platform


Advanced the Phase 1/2 MYCHELANGELO I clinical trial evaluating OTX-2002 in patients with hepatocellular carcinoma (HCC):
o
OTX-2002 continues to advance in monotherapy dose escalation.
o
As of March 24, 2024, data from the first three cohorts (0.02 mg/kg – 0.06 mg/kg) showed:

OTX-2002 continued to be generally well tolerated, with no dose-limiting toxicities observed.

Consistent dose-dependent pharmacokinetics with no drug accumulation observed following repeat doses.

All patients demonstrated controlled modulation and downregulation of MYC mRNA expression, an important oncogene regulating cell function and cell death.

The interim disease control rate (DCR) for the target population of HCC patients was 80%, reflecting 4 out of 5 efficacy-evaluable patients having a best overall response of stable disease. These patients had an average of three or more previous therapies and entered the trial with a life expectancy of less than 12 weeks. The DCR for patients with non-HCC solid tumors in the trial (n=5) was 40%, indicating the potential specificity of OTX-2002 for HCC.
o
The Company continues to evaluate patients with HCC in Cohort 4 at the 0.12 mg/kg dose level, which recently cleared the 28-day dose limiting toxicity (DLT) window. Based on preclinical experience and modeling, Omega believes this dose level is within the expected active dose range. In March 2024, the Company opened enrollment for Cohort 5 at a dose level of 0.3 mg/kg.
o
Omega expects to report additional updated clinical data from monotherapy dose escalation in mid-2024.
o
The Company plans for expansion into monotherapy and combination settings in mid-2024.

Announced research collaboration with Novo Nordisk to develop a novel therapeutic for obesity management:
o
The collaboration will leverage Novo Nordisk’s expertise in research and development within cardiometabolic diseases and Omega’s proprietary platform technology to develop an epigenomic controller designed to enhance metabolic activity.
o
Unlike traditional approaches focused on appetite suppression, the program aims to leverage precision epigenomic control to enhance thermogenesis, a naturally occurring metabolic process that burns calories.
o
Under the terms of the agreement, Novo Nordisk will reimburse all R&D costs and has the right to select one target to advance for clinical development.

Omega and Flagship’s Pioneering Medicines are eligible to receive up to $532 million in upfront, development and commercial milestone payments, as well as tiered royalties on annual net sales of a licensed product, which will be split equally between the parties.

Continued to advance and expand OMEGA platform capabilities:
o
Presented new preclinical data supporting the breadth of Omega’s platform capabilities, including bidirectional and multiplexed epigenomic control of gene expression in liver inflammation and fibrosis at the American Association for the Study of Liver Diseases’ (AASLD) The Liver Meeting 2023.

A HNF4A-targeting epigenomic controller led to a durable increase in HNF4α expression, preferential upregulation of HNF4α P1 promoter isoforms, and reduced key measures of fibrosis both in vitro and in vivo, supporting this development candidate’s potential for the treatment of fibrotic liver disease.

In preclinical models, liver-specific multiplexed targeting of CXCL9, CXCL10 and CXCL11 via an epigenomic controller led to a significant reduction in T-cell migration, a critical driver of inflammation-induced liver injury, supporting the potential of this approach as a novel treatment for inflammatory liver diseases.

Corporate


Announced cost reduction and strategic prioritization initiative to maximize near- and long-term value creation opportunities:
o
Following a strategic review, the Company has focused its pipeline and reduced overall headcount by approximately 35%. These fiscally disciplined actions are expected to extend the Company’s cash runway into Q1 2025.
o
Positions the Company to achieve key clinical data readouts from the monotherapy dose escalation and dose expansion stages of the MYCHELANGELO I clinical trial.
o
The Company will prioritize certain preclinical programs and platform efforts:

Prioritized preclinical programs include OTX-2101 for non-small cell lung cancer (NSCLC), the HNF4A program in liver regeneration, and development of an epigenomic controller for obesity in collaboration with Novo Nordisk.

Core work on platform biology, epigenomic controllers, and characterization of LNP delivery to the lung and other tissues will continue.
o
An updated corporate presentation is available on the Investors section of the Company’s website at View Source

Fourth Quarter and Full Year 2023 Financial Results

As of December 31, 2023, the Company had cash, cash equivalents and marketable securities totaling $73.4 million, which is expected to fund operations into Q1 2025.

Research and development (R&D) expenses for the fourth quarter of 2023 were $15.5 million, compared to $26.0 million for the fourth quarter of 2022. R&D expenses for 2023 were $77.2 million compared to $81.2 million in 2022. The $4.0 million decrease in R&D expenses in 2023 compared to 2022 was primarily due to lower external research and manufacturing costs, consulting and professional fees, and lab expenses, partially offset by an increase in personnel-related expenses, including stock-based compensation to support business growth, and facilities and other costs.

General and administrative (G&A) expenses for the fourth quarter of 2023 were $6.2 million, compared to $5.7 million for the fourth quarter of 2022. G&A expenses for 2023 were $26.2 million, compared to $23.7 million in 2022. The $2.5 million increase in G&A expenses in 2023 compared to 2022 was primarily due to higher professional and consulting fees, and facilities and other administrative costs.

Net loss for the fourth quarter of 2023 was $20.2 million, compared to $30.8 million for the fourth quarter of 2022. Net loss for the year ended December 31, 2023, was $97.4 million, compared to a net loss of $102.7 million for the year ended December 31, 2022. The decrease in net loss for 2023 compared to 2022 was primarily due to decreases in R&D expenses.

Moleculin to Present at the MedInvest Biotech & Pharma Investor Conference

On March 28, 2024 Moleculin Biotech, Inc., (Nasdaq: MBRX) (Moleculin or the Company), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting hard-to-treat tumors and viruses, reported Walter Klemp, President and Chief Executive Officer of Moleculin will present at the MedInvest Biotech & Pharma Investor Conference behind held in New York City, NY on Thursday, April 4, 2024 at 4:10 PM ET (Press release, Moleculin, MAR 28, 2024, View Source [SID1234641573]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In addition to the presentation, management will be available to participate in one-on-one meetings with qualified members of the investor community who are registered to attend the conference. For more information about the event, please visit the conference website.

A live webcast of the event will be available on the Events page in the Investors section of the Company’s website (moleculin.com).

Molecular Templates Announces $9.5 Million Private Placement Offering and Agreement to Amend Second Tranche of July 2023 Purchase Agreement

On March 28, 2024 Molecular Templates, Inc. (Nasdaq: MTEM, "Molecular Templates," or "MTEM"), a clinical-stage biopharmaceutical company focused on the discovery and development of proprietary targeted biologic therapeutics, known as engineered toxin bodies, to create novel therapies with potent and differentiated mechanisms of action for cancer, reported that it has entered into a definitive amended and restated securities purchase agreement with certain healthcare investors that will provide $9.5 million in gross proceeds to MTEM through the closing of the second tranche of its previously announced July 2023 private placement and purchase agreement on amended terms (Press release, Molecular Templates, MAR 28, 2024, View Source [SID1234641572]). The financing is being led by existing investor BVF Partners L.P. and includes existing investors BB Biotech AG and Santé, and other leading institutional investors.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

At the closing of the second tranche, MTEM expects to issue an aggregate of 1,209,612 shares of its common stock (and, in lieu thereof, prefunded warrants to purchase 2,460,559 shares of common stock) and accompanying warrants to purchase up to an aggregate of 7,340,342 shares of its common stock (or prefunded warrants in lieu thereof) at a combined purchase price of $2.60 per share and accompanying warrants, in accordance with the "Minimum Price" requirement as defined in the Nasdaq rules. The closing of the second tranche is subject to the satisfaction of customary closing conditions.

Stifel is acting as the sole placement agent in connection with the financing.

MTEM intends to use the net proceeds from the proceeds of the second tranche to fund its ongoing clinical studies, working capital and for general corporate purposes.

The securities sold in the second tranche, including the shares of common stock underlying the warrants, are being made in a transaction not involving a public offering and have not been registered under the Securities Act of 1933, as amended, or applicable state securities laws and may not be reoffered or resold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Securities Act and applicable state securities laws. MTEM has agreed to file a resale registration statement with the Securities and Exchange Commission registering the resale of the securities issued in the second tranche.

This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

European Commission Approves Merck’s KEYTRUDA® (pembrolizumab) Plus Chemotherapy as Neoadjuvant Treatment, Then Continued as Monotherapy as Adjuvant Treatment, for Resectable Non-Small Cell Lung Cancer (NSCLC) at High Risk of Recurrence in Adults

On March 28, 2024 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, in combination with platinum-containing chemotherapy as neoadjuvant treatment, then continued as monotherapy as adjuvant treatment, for resectable non-small cell lung cancer (NSCLC) at high risk of recurrence in adults (Press release, Merck & Co, MAR 28, 2024, View Source [SID1234641571]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

This approval by the EC follows the positive recommendation from the Committee for Medicinal Products for Human Use received in February 2024 and was based on results from the Phase 3 KEYNOTE-671 trial. At a median follow-up of 29.8 months (range, 0.4 to 62.0 months), KEYTRUDA plus chemotherapy in the neoadjuvant setting followed by KEYTRUDA as monotherapy after surgical resection significantly improved overall survival (OS), reducing the risk of death by 28% (HR=0.72 [95% CI, 0.56-0.93]; one-sided p=0.00517) in patients with resectable stage II, IIIA or IIIB NSCLC versus placebo plus chemotherapy in the neoadjuvant setting followed by placebo after surgical resection, regardless of PD-L1 expression. For patients who received the KEYTRUDA-based regimen, median OS was not reached (95% CI, NR-NR) versus 52.4 months (95% CI, 45.7-NR) for patients who received the chemotherapy-placebo regimen. The KEYTRUDA-based regimen also improved event-free survival (EFS), reducing the risk of disease recurrence, progression or death by 41% (HR=0.59 [95% CI, 0.48-0.72]) compared to the chemotherapy-placebo regimen. For patients who received the KEYTRUDA-based regimen, median EFS was improved by nearly two and a half years compared to the chemotherapy-placebo regimen (47.2 months [95% CI, 32.9-NR] versus 18.3 months [95% CI, 14.8-22.1], respectively).

"Despite the clinical advances for patients with metastatic lung cancer, lung cancer continues to be the leading cause of cancer death in Europe, reinforcing the need to treat these patients in earlier stages of their disease, where we may have the most impact," said Dr. Solange Peters, chair of the medical oncology and thoracic malignancies department, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. "The approval of this KEYTRUDA-based regimen is an important milestone for patients diagnosed with resectable non-small cell lung cancer at high risk of recurrence, regardless of PD-L1 expression, providing a new option for these patients that has shown, through the results of the Phase 3 KEYNOTE-671 trial, the potential to help extend their lives."

This approval allows marketing of this KEYTRUDA regimen for this indication in all 27 EU member states, as well as Iceland, Liechtenstein, Norway and Northern Ireland. KEYTRUDA is now approved for six indications in NSCLC, and for 27 indications overall in the EU. In October 2023, KEYTRUDA was approved in the U.S. for the treatment of patients with resectable (tumors ≥4 cm or node positive) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.

"Today’s approval of the first anti-PD-1/L1 therapy as part of a treatment regimen in Europe for the neoadjuvant followed by adjuvant treatment of resectable NSCLC based on positive overall survival results demonstrates our continued progress to advance treatments in earlier stages of lung cancer," said Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. "We are eager to build on this momentum as we plan to seek additional approvals of this regimen around the world, and to work together with the cancer community to help drive earlier diagnoses of lung cancer, an urgent need."

About the KEYNOTE-671 study design

KEYNOTE-671 is a randomized, double-blind Phase 3 trial (ClinicalTrials.gov, NCT03425643) evaluating KEYTRUDA in combination with neoadjuvant chemotherapy, followed by surgery and continued adjuvant treatment with KEYTRUDA as a single agent, versus placebo plus neoadjuvant chemotherapy, followed by resection and adjuvant placebo, in patients with resectable stage II, IIIA or IIIB (T3-4N2) NSCLC (per the eight edition of the American Joint Committee on Cancer [AJCC] Cancer Staging Manual). The trial’s dual primary endpoints are EFS, per RECIST v1.1 by investigator assessment, and OS. Key secondary endpoints include pathologic complete response (pCR) and major pathological response (mPR). The study enrolled 797 patients who were randomly assigned (1:1) to receive either:

KEYTRUDA (200 mg intravenously [IV] every three weeks [Q3W]) plus chemotherapy (cisplatin [75 mg/m2, IV; given on Day 1 of each cycle] and either gemcitabine [1,000 mg/m2, IV; given on Days 1 and 8 of each cycle] or pemetrexed [500 mg/m2, IV; given on Day 1 of each cycle]) for up to four cycles as neoadjuvant therapy prior to surgery. Within 4-12 weeks following surgery, KEYTRUDA (200 mg) was administered every three weeks for up to 13 cycles, or;
Placebo (saline IV Q3W) plus chemotherapy (cisplatin [75 mg/m2, IV; given on Day 1 of each cycle] and either gemcitabine [1,000 mg/m2, IV; given on Days 1 and 8 of each cycle] or pemetrexed [500 mg/m2, IV; given on Day 1 of each cycle]) for up to four cycles as neoadjuvant therapy prior to surgery. Within 4‑12 weeks following surgery, placebo was administered every three weeks for up to 13 cycles.
About lung cancer

Lung cancer is the leading cause of cancer death worldwide. In 2022 alone, there were approximately 2.4 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 80% 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.