On August 15, 2024 LIXTE Biotechnology Holdings, Inc. ("LIXTE" or the "Company") (Nasdaq: LIXT and LIXTW), a clinical stage pharmaceutical company, reported it will be presenting at two investor conferences (Press release, Lixte Biotechnology, AUG 15, 2024, View Source [SID1234645984]):

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■ The Investor Summit Summer 2024 Virtual Conference Tuesday, August 20, 2024, at 2 p.m. EDT/11 a.m. PDT. To access the presentation, visit LIXTE’s investor relations website at View Source

■ The H.C. Wainwright 26th Annual Global Investor Conference, on demand starting at 7 a.m. EDT/4 a.m. PDT, September 9-11, 2024. To access the virtual presentation, register for the conference at www.hcwevents.com/annualconference.

Bas van der Baan, CEO of LIXTE, will present an overview of the Company’s clinical trials with LB-100, its proprietary compound focused on enhancing chemotherapy and immunotherapy treatments as cancer therapies. Proof-of-concept clinical trials are currently in progress for colorectal, ovarian and sarcoma cancers, including trials funded by GSK and Roche.

On August 15, 2024 Nuntius Therapeutics ("Nuntius"), a biotech company developing transformative mRNA therapies through their advanced delivery technology, reported that they have entered into a collaboration agreement with Taiho Pharmaceutical Co., Ltd. ("Taiho"), a leading company in Japan for developing innovative medicines for the treatment of cancer (Press release, Nuntius Therapeutics, AUG 15, 2024, View Source [SID1234645957]). Taiho will use Nuntius’ cell-specific peptide dendrimer- and lipid-based nanocarriers to develop novel mRNA cancer immunotherapies.

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The collaboration agreement follows a successful feasibility study which evaluated Nuntius’ delivery capabilities.

"We are thrilled to embark on this collaboration with Taiho to improve treatments for cancer patients. Taiho is an excellent partner for us given their strong oncology focused research and commercial capabilities," said Benita Nagel, CEO & Co-Founder of Nuntius.

"Delivery remains a major challenge for mRNA therapies. This agreement validates our nanocarriers as an exceptionally effective cell-specific delivery technology for genetic medicines," added Albert Kwok, PhD, CSO & Co-Founder of Nuntius.

The financial terms of the collaboration agreement were not disclosed.

Nuntius’ programmable and scalable nanocarriers can effectively and safely target cell types beyond the liver and outperform leading delivery technologies. The company recently published its machine learning approach to discovering high-performing mRNA nanocarriers in the journal Advanced Science. Nuntius’ high-throughput, in silico screening of delivery vehicle candidates significantly reduces the time and cost required to bring mRNA therapies to the clinic.

On August 15, 2024 EnPlusOne Biosciences, Inc., a biotechnology company harnessing the power of enzymes to deliver better RNA at scale, reported that it is part of a collaboration led by the Wyss Institute for Biologically Inspired Engineering at Harvard University that has been awarded an agreement for up to $27 million by the Advanced Research Projects Agency for Health (ARPA-H) (Press release, EnPlusOne Biosciences, AUG 15, 2024, View Source [SID1234645955]). The agreement covers multi-disciplinary efforts to develop a disease-agnostic novel RNA therapeutic with the potential to treat diverse diseases, including types of cancer and infectious diseases, and to be effectively and rapidly deployable. Initially, up to $3.5 million of the agreement is focused on the EnPlusOne enzymatic platform.

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ARPA-H is a federal funding agency which funds transformative biomedical and health research breakthroughs, translating prioritized research from the lab to applications in the marketplace. The ARPA-H award will allow the Wyss Institute team to significantly accelerate and expand efforts to advance the therapy towards an Investigational New Drug (IND) submission to the Federal Food and Drug Administration (FDA).

The team is initially focusing on cancer and will explore the platform’s potential for difficult-to-treat infectious diseases. The ARPA-H project will build on a newly developed Duplex RNA technology and leverage the powerful RNA delivery capabilities developed by groups at the Wyss Institute, along with the groundbreaking enzymatic RNA synthesis capabilities of EnPlusOne to optimize the RNA’s design and scalability.

Dan Ahlstedt, co-founder and Chief Operating Officer said, "We come full circle rejoining our Wyss colleagues for this exciting collaboration. This comprehensive program will give us the opportunity to demonstrate how enabling modifications and limitless scale can be unlocked by our ezRNA platform. We are grateful to the Wyss Institute and ARPA-H for recognizing the current problems facing RNA manufacturing and sharing our vision that an enzymatic approach is the future. We look forward to progressing our platform alongside this team as we collectively work to address critical human health challenges."

Wyss Institute Core Faculty member Natalie Artzi, Ph.D. is the lead-investigator on the project with co-principal investigator and Wyss Institute Founding Director Don Ingber, M.D., Ph.D. Artzi also is Associate Professor of Medicine at Harvard Medical School (HMS) and Brigham and Women’s Hospital and a Principal Research Scientist at MIT. Additional key investigators include Wyss Institute Director of Translational R&D Kenneth Carlson, Ph.D., a drug discovery and development specialist with extensive industry experience, and Wyss Institute Core Faculty member William Shih, Ph.D., who developed a DNA origami platform that allows the precise and highly effective presentation of RNA drugs, cancer and pathogen-derived antigens, and immune activating adjuvants to the immune system. Shih’s team will provide their DNA nanotechnology approach as an additional drug delivery option.

The collaboration is another validation of the potential for enzymatic synthesis to address the needs of a rapidly expanding RNA therapeutic market as the industry faces demand for RNA production that cannot be met by chemical synthesis alone. It builds upon recent important progress shared by EnPlusOne, including the breakthrough synthesis of the antisense strand of the commercially approved siRNA drug, Leqvio (inclisiran), a treatment for hypercholesteremia (high cholesterol) licensed from Alnylam Pharmaceuticals, Inc. by Novartis, that currently addresses a multi-million patient population.

EnPlusOne was launched by the Wyss Institute in 2022 to commercialize its enzymatic RNA oligonucleotide synthesis technology developed in the laboratory of co-founder George Church, PhD. Seed financing was led by Northpond Ventures, with participation from Breakout Ventures, Coatue, and individual investors.

On August 15, 2024 Aarvik Therapeutics, a biotechnology company dedicated to engineering precision medicines for cancer therapy, reported that its collaboration partner ArriVent BioPharma, Inc. has exercised the option to exclusively license the collaboration program (Press release, Aarvik Therapeutics, AUG 15, 2024, View Source [SID1234645954]).

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As part of the research collaboration agreement entered into between Aarvik and ArriVent on December 21, 2021, Aarvik has been responsible for discovery and preclinical development of a novel ADC molecule that relies on the unique modular platform developed by Aarvik. ArriVent will be responsible for clinical development and commercialization. Aarvik has received an upfront payment, research funding and an opt-in payment, and is eligible to receive contingent development and commercial milestones, plus royalties.

"Aarvik has shown that it can combine the most advanced protein engineering technologies with deep ADC drug development expertise to enable next-generation, best-in-class oncology therapies," said Jagath Reddy Junutula, PhD, Co-founder, President and CEO of Aarvik Therapeutics. "Aarvik will continue to pursue previously hard-to-treat indications through the power of its novel multi-targeting platforms."

"We are delighted to see Aarvik reach this significant milestone," said Sachdev Sidhu, PhD, Co-founder and Board member of Aarvik Therapeutics. "This provides further validation and underscores the power and potential of Aarvik antibody platforms and deep protein engineering capabilities."

On August 15, 2024 TriSalus Life Sciences Inc., (Nasdaq: TLSI), an oncology company integrating novel delivery technology with immunotherapy to transform treatment for patients with liver and pancreatic tumors, reported its financial results for the second quarter ended June 30, 2024, and provided a business update (Press release, TriSalus Life Sciences, AUG 15, 2024, View Source [SID1234645953]).

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Mary Szela, President and Chief Executive Officer of TriSalus Life Sciences, stated, "We concluded the second quarter with robust revenue growth and effective execution across our operations. Our sustained revenue growth underscores the critical demand for our Pressure Enabled Drug Delivery technology (PEDD ). We are excited to launch the DELIVER program, which will showcase the advantages of our TriNav system in treating a diverse array of complex patients."

"Additionally, we have successfully advanced development of nelitolimod, having treated 100 patients in four indications and three clinical trials using our PEDD technology. Our progress to date indicates that nelitolimod can be delivered to the liver and pancreas with minimal systemic exposure and shows early promise of benefit in heavily pretreated patients with advanced disease," added Ms. Szela. "We anticipate further growth of our PEDD technology and TriNav system and look forward to presenting our final Phase 1 data for uveal melanoma liver metastases and locally advanced pancreatic cancer in the fourth quarter."

Second Quarter Business Update

DELIVER Program

TriSalus is excited to unveil the DELIVER program, a series of clinical trials designed to significantly expand the addressable market by evaluating the use of the TriNav system across a diverse range of complex patient populations, with the intent to further validate prior clinical studies that demonstrated the favorable clinical effects of the PEDD technology. This initiative aims to generate comprehensive data and solidify the evidence supporting TriNav’s application in patients who might not be suitable candidates for traditional transarterial chemotherapy and radioembolization treatments. A key focus of the DELIVER program is to investigate the potential of combining use of the TriNav system with these therapies to enhance effectiveness and address resistance mechanisms in challenging cancers.
The Company expects to launch the program with its first clinical study, named "PROTECT" (Pressure Enabled Retrograde Occlusive Therapy with Embolization for Control of Thyroid Disease). The goal of the trial is to highlight the advantages of this novel approach compared to conventional surgical methods.
Nelitolimod Clinical Studies in Uveal Melanoma Liver Metastases, Hepatocellular Carcinoma, Intrahepatic Cholangiocarcinoma, and Locally Advanced Pancreatic Cancer via the Pressure-Enabled Regional Immuno-Oncology (PERIO) Clinical Program

In November 2023, TriSalus presented initial Phase 1 results for the PERIO-01 and PERIO-03 studies at the Society of Immunotherapy for Cancer annual meeting, and in June 2024, it presented top-line results for PERIO-02 at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting.
PERIO-01 is a Phase 1 trial evaluating hepatic arterial delivery of nelitolimod via the PEDD technology in patients with uveal melanoma liver metastases. The trial includes dose-escalation cohorts with monotherapy and in combination with checkpoint inhibitors. The preliminary data show a tolerable safety profile, evidence of liver metastases myeloid-derived suppressor cells (MDSC) depletion with T cell infiltration, and promising indications of activity, including ctDNA responses, disease control, and survival beyond historical benchmarks in predominantly pre-treated patients. The final results for the PERIO-01 Phase 1 trial are expected in Q4 2024.
PERIO-02 focuses on the hepatic arterial delivery of nelitolimod via the PEDD technology for patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma. The study has been completed, and recent findings presented by investigators from MD Anderson Cancer Center at ASCO (Free ASCO Whitepaper) demonstrated consistent safety and immunologic effects, along with encouraging survival times in a subset of patients treated with a systemic checkpoint inhibitor doublet. The Company expects further investigation into these indications to continue only through investigator-initiated studies.
PERIO-03 is a Phase 1 dose-escalation study of nelitolimod in locally advanced pancreatic cancer. Nelitolimod is administered through outpatient interventional radiology procedures using the Pancreatic TriSalus Infusion System PEDD device. Phase 1 results for this study are anticipated in Q4 2024.
Closed up to $50 million of Debt Financing with OrbiMed to support TriNav Growth Initiatives

In April, TriSalus announced the closing of a debt financing facility with OrbiMed, a healthcare investment firm. Under the terms of the credit agreement with OrbiMed, the Company borrowed $25 million at closing. In addition, an aggregate of up to an additional $25 million is available in two tranches at the Company’s option, subject to the Company’s achievement of certain revenue thresholds.

Cash and cash equivalents on hand totaled $16.5 million on June 30, 2024. Including the Company’s Standby Equity Purchase Agreement (SEPA) and other existing sources of liquidity and assuming it achieves the revenue targets and borrow the remaining $25 million of the debt financing, the Company expects to have sufficient cash runway to fund operations through the end of 2025.

Completion of Warrant Exchange Offer

On May 24, 2024, TriSalus announced an exchange offer of 0.30 shares of Common Stock for each publicly traded and private warrant tendered.
The offer’s purpose was to simplify the Company’s capital structure and reduce the potential dilutive impact of the warrants, thereby providing the Company with more flexibility for financing its operations in the future.
On July 1st, the Company issued 2,110,366 shares of common stock in exchange for 6,529,954 (or 79%) of its publicly traded warrants and 504,685 (or 10%) of its private warrants.
Financial Results for Q2 2024

Revenue, all of which is from the sale of the TriNav system, was $7.4 million and $13.8 million, respectively, for the three and six months ended June 30, 2024, up 60% and 82%, respectively, compared to the same periods in 2023. Revenue growth was driven primarily by increased selling resources and continued market share increases.

Gross margins were 88% and 86% for the three and six months ended June 30, 2024, respectively, compared to 83% and 81%, respectively, for the same periods in 2023. The improvement in the quarter and year-to-date is due to increased factory volumes and improved operational efficiency.

Operating losses were $8.2 million and $19.9 million, respectively, for the three and six months ended June 30, 2024, respectively, compared to losses of $11.4 million and $21.6 million, respectively, for the same periods in 2023. Current year reductions in operating losses are due to increased sales, improved gross margins, and reduced research and development spending associated with the timing of clinical trial spending.

Net losses available to common stockholders were $4.3 million and $17.6 million, respectively, for the three and six months ended June 30, 2024, compared to losses of $14.0 million and $22.2 million, respectively, for the same periods in 2023. Net losses in 2024 include non-cash related losses on change in fair value of the Company’s SEPA, warrant and revenue base redemption liabilities of $9.0 million and $6.5 million, respectively for the three and six months ended June 30, 2024, compared to gains of $1.1 million and $3.5 million, respectively, for the same periods in 2023. Net losses in 2023 also include the impact of non-cash related losses on equity issuance of $4.2 million in the three and six months ended June 30, 2023. These amounts are partially offset in 2024 by the impact of non-cash related gains on the change in fair value of contingent earnout liabilities of $13.7 million and $9.7 million, respectively, for the three and six months ended June 30, 2024.

The basic and diluted loss per share for the three and six months ended June 30, 2024, were $0.21 and $0.81, respectively, compared to $35.84 and $59.79 for the three and six months ended June 30, 2023, respectively.

Conference Call

TriSalus will host a webcast to discuss its second quarter 2024 financial results and business highlights on August 15, 2024 at 9:00 a.m. EDT. The webcast can be accessed on the investor relations section of TriSalus’ website at View Source Following the conclusion of the event, a webcast replay will be available on the website for approximately 90 days. Interested parties participating by phone will need to register using this online form. After registering for the webcast, dial-in details will be provided in an auto-generated e-mail containing a link to the conference phone number and a personal pin.