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Klotho Neurosciences, Inc. (NASDAQ: KLTO) Unlocking the Anti‑Aging Power of α‑Klotho  — pioneering cell and gene therapies to transform the treatment of neurodegenerative disorders with disease‑modifying, potentially life‑extending biologics. Life-Saving Innovations. Game-Changing Investments. Why Invest in Klotho Neurosciences? First‑in‑class α‑Klotho Gene Platform Exclusive global license for a patented secreted splice variant of the α‑Klotho gene (s‑KL), with IP protection across the U.S., Europe, and China.   Rapid Clinical Advancement KLTO‑202, our lead AAV‑based α‑Klotho gene therapy for ALS, is advancing to clinical stage—manufacturing underway and IND filing expected within 8–12 months .   Clear Path in Major Markets Targeting high‑unmet-need conditions: ALS, Alzheimer’s, Parkinson’s and broader age-related cognitive decline. Aging is the number‑one risk factor for these disorders; we aim to address root causes, not symptoms .   Strong Financial Position & Compliance Restored Raised >$11M via warrant exercises, extinguished all debt, now surpassing NASDAQ shareholder‑equity thresholds. Debt‑free balance sheet ensures runway and compliance.   Experienced Leadership & Scientific Advisory Board Founded by seasoned biotech executives, with strategic partnerships anchored at UAB/ ICREA and backed by experts in gene therapy commercialization. Near‑Term Catalysts on the Horizon IND submission and launch of Phase I/II ALS program (Q3 2026).   (NASDAQ: KLTO) Innovative Platform: α‑Klotho Gene Therapy 1.      Breakthrough Biology α‑Klotho is a master “anti‑aging” regulator shown to reverse neurodegeneration, improve cognition, reduce inflammation and oxidative stress, and clear amyloid plaques in preclinical models.   2.      Multi-Delivery Technology Our s‑KL gene construct—compatible with viral vectors, lipid complexes, recombinant protein, or ex vivo cell therapy—enables versatile deployment to maximize therapeutic reach.   3.      Therapeutic Breadth Platform designed to address a spectrum of age‑related diseases: ALS, Alzheimer’s, Parkinson’s, sarcopenia, osteoporosis, cardiovascular and renal conditions. Investment Highlights - (NASDAQ: KLTO) Invest in the Future, Today Strength Details Proprietary IP Exclusive worldwide rights to s‑KL gene therapy platform Clinical Progress KLTO‑202 entering GMP manufacturing and IND timeline Financial Stability $11M capital raise, debt cleared, NASDAQ-compliant equity Experienced Team Proven track record in biotech R&D and commercialization Scalable Platform Modular gene therapy tech for multiple indications Approaching Catalysts IND submission, investor events, early-stage bio data We Don’t Just Disrupt — We Deliver (NASDAQ: KLTO) Recent Milestones $11M funds raised & debt retirement — Debt-free, equity threshold exceeded. Advancing ALS candidate  — KLTO‑202 manufacturing live; IND expected in 8–12 months Investor visibility  — Featured at Biotech Showcase 2025 during JPM Week. Vision & Strategy Klotho Neurosciences is on a mission to reshape the future of brain health . By harnessing our patented α‑Klotho gene therapy, we aim to deliver life-changing, disease-altering treatments across neurodegenerative conditions. Our approach integrates: Robust clinical pipeline  with ALS lead candidate Expansion potential (Alzheimer’s, Parkinson’s, diagnostics) Partner and licensing opportunities to accelerate development Scalable infrastructure supporting commercialization goals Join Us in Defining the Next Era of Neurotherapeutics Klotho offers: A compelling science‑backed platform with broad therapeutic reach Upcoming milestones  set to significantly increase value Solid financial footing  with minimal dilution risk Experienced leadership  and scalable operational focus   We invite forward-looking investors to engage with our vision, support our clinical journey, and shape the future of disease-modifying neurotherapeutics.   (NASDAQ: KLTO) Contact Investor Relations Email: IR@klothoneuro.com  | Jeff LeBlanc, CFO DISCLAIMER This landing page is intended for informational purposes only and does not constitute investment advice. Forward-looking statements are made under the safe harbor provisions of relevant securities legislation. Snapmediagroup.net  and Vanderbiltreport.com  are owned and operated by SMG a US-based corporation. We have received compensation of up to $100,000 for the profiling of Klotho Neurosciences, Inc.  (Nasdaq: KLTO)  starting on July , 2025. It is important to note that we do not own any shares in KLTO : NASDAQ .

OTC: FAGI Invest in FULL ALLIANCE GROUP. (OTC: FAGI) Full Alliance Group, Inc. (FAGI ) (OTC) offers a compelling investment opportunity as a diversified holding company engaged in high-growth sectors such as healthcare, nutraceuticals, cosmeceuticals, and financial services. The company employs a strategic approach to acquiring and developing innovative businesses, utilizing vertical integration to enhance operational efficiency and profitability. Why Invest in FAGI? Here is one Company to keep your eyes on! With a robust leadership team, an expanding market presence, and scalable business models, FAGI is well-positioned for sustained long-term growth. Investors looking to gain exposure to dynamic industries with significant revenue potential should consider FAGI, given its unwavering commitment to innovation, operational excellence, and maximizing shareholder value. This stock is a Sleeping Giant Strengths & Competitive Advantages 1.      Platform Manufacturer with FDA-Registered Facility, 25,000 sq ft Tampa production plant capable of branded and white-label manufacturing—providing scalability & regulatory compliance.   2.      Versatile Tech-Enabled Product Suite Nanobubble HOCl for superior antimicrobial stability & safety Regenerative dermal and health serums, Direct-to-consumer nutraceutical pathway via digital JV   3.      Scalable, Multi-Channel Go-to-Market Model Revenue streams supported by B2B/ white-label deals, retail rollouts, D2C platforms, and digital-affiliate marketing.   4.      Local Production & Supply Chain Control Tampa-based manufacturing ensures fast delivery, quality oversight, and cost control. Strategic Opportunities Ahead ·         Licensing & Private-Label Expansion:  Aquaox targeting new partnerships across hygiene, skincare, and agriculture.   ·         Rapidly Growing HOCl Demand:  Clean-label, non-toxic sanitizing solutions are increasingly favored post‑pandemic.   ·         D2C Brand Rollout:  JV with FV Products will launch nutraceutical & cosmeceutical brands, enabling immediate e-commerce reach.   ·         Regenerative Health Momentum:  Via DynaMAXX’s clinical network and expanding PRiVIVE reach.   ·         Scalability & Margins:  Facility upfront investments leading to growing production volume and margin leverage. Leadership & Investor Accessibility Leadership Team:  Experienced leadership across biotech, clean-tech, and digital commerce.   Transparency:  Subsidiary-focused earnings updates and ongoing IR engagement through hometown facility.   Investor Relations:  Regular updates through press releases Diverse Product Portfolio Full Alliance Group, Inc.   (OTC: FAGI) – Building a healthier, safer, and more vibrant world—one innovative solution at a time. Don't Miss Out:  Invest Today - INVEST WITH US, WHERE OPPORTUNITY MEETS GROWTH Ready to Invest? Join us in revolutionizing distribution and seizing opportunities in high-growth markets. (Learn More (OTC: FAGI) Today INVEST IN YOUR FUTURE - CALL YOUR BROKER NOW Given these factors, investing in (OTC: FAGI) might be a strategic move for those looking to be part of the next wave of technological innovation. DISCLAIMER Snapmediagroup.net and Vanderbiltreport.com are owned and operated by SMG a US-based corporation. We have received compensation of up to $100,000 for the profiling of Full Alliance Group, Inc. (OTC: FAGI). It is important to note that we do not own any shares in FAGI :OTC.

Prenetics (NASDAQ: PRE), a leading genomics-driven health sciences company, is revolutionizing prevention, early detection, and treatment. Our prevention arm, CircleDNA, uses whole exome sequencing to offer the world’s most comprehensive consumer DNA test. Our $200 million joint venture with renowned scientist Prof. Dennis Lo, underscores our unwavering commitment to saving lives through pioneering multi-cancer early detection technologies. Lastly, ACT Genomics, our treatment unit, is the first Asia-based company to achieve FDA clearance for comprehensive genomic profiling of solid tumors via ACTOnco. Each of Prenetics’ units synergistically enhances our global impact on health, truly embodying our commitment to enhancing life through science.

Why Totaligent, Inc. (OTC: TGNT) is the Exciting Investment Opportunity You Haven't Heard About Yet Totaligent, Inc. is an innovative technology company that harnesses the power of big data through a variety of cutting-edge platforms. From email and SMS to Social Media and programmatic advertising, we utilize a range of tools including short-code and push notifications to deliver highly targeted digital marketing solutions for organizations of all sizes. At Totaligent (OTC: TGNT) , we are revolutionizing the way businesses connect with their target audience. Our person-based digital marketing platform empowers organizations to leverage their data and tap into new sources to promote their products, services, and brands with unprecedented efficiency. An early-stage AI disruptor with massive potential—invest now and ride the wave of intelligent automation. Totaligent’s AI ecosystem is built for long-term growth, offering unparalleled efficiency and data-driven advantage M Market Opportunity and Highlights Totaligent, Inc. (OTC: TGNT) is a technology company specializing in person-based digital marketing services for companies and individuals in the United States. The company offers managed campaigns to publicly traded companies and political candidates. In 2023, Totaligent reported a significant revenue increase to $731,679, up 3,652% from $19,500 in the previous year . The company also reduced its losses by 32% to $402,170 in 2023. As of February 14, 2025, Totaligent's stock price was $0.0400, reflecting a 90.48% increas e from the previous close. The company's market capitalization stands at $3.65 million, with 172.91 million shares outstanding. In December 2024, Totaligent successfully completed PCAOB audits for fiscal years 2022 and 2023, resuming SEC reporting as a voluntary filer. Investors may find Totaligent appealing due to its substantial revenue growth, improved financial performance, and commitment to regulatory compliance. why investors should invest in Totaligent, Inc, https://www.totaligent.com/investors/ Totaligent, Inc. (OTC: TGNT) is a technology company specializing in AI-powered, person-based digital marketing solutions. The company has recently achieved significant milestones that may appeal to investors: Totaligent, Inc. (OTC: TGNT) stands out not just as a digital marketing firm, but as a leader in person-based marketing innovation. Their focus on personalization, coupled with advanced technology and a proven track record, offers a remarkable investment opportunity that many may still overlook. For investors seeking a blend of security, growth potential, and alignment with market trends, Totaligent presents a noteworthy option. As the digital marketing landscape expands, investing in a company at the forefront of this evolution could yield substantial dividends. Invest in Totaligent today and be part of the exciting future of marketing! DISCLAIMER Snapmediagroup.net  and Vanderbiltreport.com  are owned and operated by SMG a US-based corporation. We have received compensation of up to $1,500 from Totaligent, Inc. (Nasdaq: TGNT)  starting on Frebuary 14, 2025. It is important to note that we do not own any shares in TGNT: NASDAQ .

(CSE: ARGO | OTCQB: ARLSF | Frankfurt: 94Y0) Pioneering Sustainable, High‑Performance Materials Formerly Argo Living Soils Corp. , Argo Graphene Solutions Corp. rebrands to emphasize its leadership in graphene‑infused solutions for construction, agriculture, and infrastructure . Key Milestones Name change effective July 8, 2025 ; trading under ARGO/ARLSF/94Y0 continues with new CUSIP (04021P101) & ISIN (CA04021P1018). New website live , www.argographene.com , launched.   Core Business Verticals 1. Graphene‑Enhanced Concrete & Asphalt First graphene purchase order : 1,000 L of 0.04% graphene‑oxide liquid for high-performance concrete applications shows immediate supply-chain traction.  Argo Green Concrete Solutions Inc.  (Nevada): developing bio‑graphene concrete that's twice as strong and four times more water‑resistant, with lower CO₂ emissions . Collaboration with Graphene Leaders Canada : extending R&D to asphalt—targeting an $82 billion market—with enhanced durability & reduced environmental impact. 2. Sustainable Agri‑Inputs MOU with AGIC : commercializing graphene‑based biofertilizers using proprietary graphene-on-biomass technology aimed at boosting yields and reducing environmental impact. Competitive Advantages Integrated vertical model : from graphene sourcing to end-use solutions in concrete, asphalt, and fertilizers. Global certification roadmap : North America traction now, with plans for EU and German regulatory approval. Low-carbon footprint : aligns with global green policies and sustainable infrastructure trends. Robust capital support : Raised C$302,975 in private placement; C$710,600 from warrant exercises since Feb 2025. Market Opportunity Concrete market : A $250 billion+ addressable market driven by green infrastructure—EU Green Deal and U.S. climate mandates create strong tailwinds. Asphalt market : Targeting an $82 billion global sector poised for innovation. Agriculture input market : Rising demand for sustainable yields and bio-based fertilizers enhances long-term growth potential. Strategic Partnerships Graphene oxide supplier : stable supply of high-grade materials for product development. Graphene Leaders Canada : co-developing asphalt solutions via advanced nanoplatelet dispersion technologies. PT. AGIC : pioneering bio-graphene fertilizer technologies. Leadership & Governance Scott Smale , President & CEO: overseeing strategic pivot and rebranding Robert Intile , CEO (prior): led early graphene integration, MOU with AGIC, and green concrete expansion. Investor relations & marketing : engaged respected firms (MarketSmart, King Tide, Apaton, Rain Communications) to scale awareness and investor outreach. Financial Health & Support Category Amount (CAD) Private Placement Funding 302,975 Warrant Exercises 710,600 Backed by capital to accelerate R&D, certify products, and expand commercialization. Strategic Roadmap Q3 2025 : Initiate concrete and asphalt pilot tests; ramp up graphene oxide imports. By late 2025 : Initiate applications for EU construction certifications. 2026 : Scale manufacturing, increase distribution, expand sales in North America and Europe. 2027+ : Pursue growth into agri-inputs and other industrial graphene applications. Why Invest? First‑mover in green graphene materials : uniquely positioned with technical assets and market reach. Massive addressable markets : $250B concrete + $82B asphalt + global ag‑input expansion. Capable leadership + aligned funding : seasoned team, strong capital base, and investor communications strategy. Sustainability alignment : clear ESG value prop for green materials, carbon-friendly infrastructure, and bio-based agriculture. Invest With Confidence Investors in ARGO / ARLSF / 94Y0 gain exposure to a triple-threat of sustainable innovation: Graphene-enhanced concrete Graphene-infused asphalt Graphene-enabled agriculture With established supply, pilot-stage rollouts, and global certification on deck, Argo Graphene Solutions is poised to deliver long-term shareholder value. DISCLAIMER Snapmediagroup.net  and Vanderbiltreport.com  are owned and operated by SMG a US-based corporation. We have received compensation of up to $100,000 from KTM regarding the profiling of Argo Living Soils  ((CSE: ARGO) (OTC Pink: ARLSF) starting on July 2025. It is important to note that we do not own any shares in (CSE: ARGO) (OTC Pink: ARLSF).

Why Investors Should Consider Coeptis Therapeutics Holdings Inc. (NASDAQ: COEP) DON'T MISS THIS OPPORTUNITY A Strategic Pivot into High-Growth Sectors Coeptis Therapeutics Holdings Inc. (NASDAQ: COEP) is undergoing a transformative shift its origins as a biopharmaceutical company to a diversified entity embracing cutting-edge technologies. The company's recent initiatives include the launch of the COEP Venture Group, aimed at investing in disruptive technologies such as artificial intelligence (AI) and robotic process automation (RPA) . This strategic pivot positions Coeptis to capitalize on high-growth sectors beyond traditional pharmaceuticals.( investors.coeptistx.com , stockinsights.ai ) Innovative Cell Therapy Platforms Despite its diversification, Coeptis continues to advance its biopharmaceutical endeavors. The company is developing innovative cell therapy platforms for cancer treatment, including CD38-GEAR-NK, an autologous, gene-edited natural killer (NK) cell-based therapeutic, and CD38-Diagnostic, an in vitro screening tool designed to identify patients likely to benefit from targeted anti-CD38 monoclonal antibody therapies . These platforms have the potential to disrupt conventional treatment paradigms and improve patient outcomes.( Nasdaq , www.alphaspread.com , Annual Reports ) Strategic Merger with Z Squared Inc. In a significant move, Coeptis has entered into a definitive merger agreement with Z Squared Inc., a Dogecoin mining company. This merger will make Z Squared a wholly-owned subsidiary of Coeptis, with plans to spin out its biopharmaceutical operations and rebrand as Z Squared, Inc. The combined company aims to enhance Dogecoin mining capabilities and capitalize on the growing digital asset market .( Nasdaq ) Robust Financial Backing Coeptis has demonstrated strong financial support through successful funding rounds. The company recently closed a $10 million Series A Preferred financing round, reinforcing its commitment to technological innovation and AI integration ( PR Newswire ). Additionally, a prior $4.3 million Series A Preferred offering was led by CJC Investment Trust, an entity controlled by board member Christopher Calise ( PR Newswire ). INVESTMENT ALERT Investment Highlights Diversified Portfolio : Transitioning into high-growth sectors like AI, RPA, and digital assets. Innovative Therapies : Developing next-generation cell therapy platforms for oncology. Strategic Partnerships : Merging with Z Squared Inc. to enter the cryptocurrency mining space.( Nasdaq ) Financial Strength : Secured substantial funding to support growth and innovation initiatives. BUY NOW Call your Broker now! Learn More For more information, visit the Investor Relations page of Coeptis Therapeutics Holdings Inc. DISCLAIMER Snapmediagroup.net  and Vanderbiltreport.com  are owned and operated by SMG a US-based corporation. We have not received any compensation regarding the profiling of Coeptis Therapeutics Holdings Inc.   (Nasdaq: COEP).  It is important to note that we do not own any shares in COEP: NASDAQ .

Invest in GPO Plus, Inc. (OTCQB: GPOX) Revolutionizing Distribution with AI-Driven Solutions Why Invest in GPOX? - HERE IS ONE COMPANY TO KEEP YOUR EYE ON! GPO Plus, Inc. (OTCQB: GPOX) is an innovative distributor transforming the convenience store and gas station sectors through its AI-powered Direct Store Delivery (DSD) model. With a focus on high-demand consumer products and a commitment to operational excellence, GPOX offers investors a unique opportunity in a rapidly growing market. Key Investment Highlights Explosive Revenue Growth : Achieved a 560% year-over-year revenue increase, reaching $4.35 million in annual revenue. AI-Powered Operations : Deployed PRISM+, an AI-driven platform optimizing delivery routes, inventory management, and operational efficiency. Strategic Expansion : Added 52 TXB convenience store locations in Texas, with plans to expand to 2,000 retail locations. Scalable Business Model : Focused on the fragmented 15%-20% of convenience store products, representing a $50 billion market opportunity. Innovation at the Core GPOX leverages its proprietary technology platform, PRISM+, to streamline operations and enhance decision-making. This AI-driven system enables precise inventory tracking, optimized delivery routes, and real-time analytics, reducing overhead costs and increasing profitability. Growth Strategy GPOX's growth strategy includes: Climate-Controlled Warehousing : Upgrading facilities to support a broader product range and increase annual revenues by $3 to $5 million. Retail Network Expansion : Utilizing existing delivery routes to add over 2,000 new retail locations, focusing on underserved markets. Call Center Sales Team : Establishing a dedicated team to reach independent stores, aiming for monthly sales of $50,000 to $100,000 per seat. Diverse Product Portfolio GPOX operates multiple Group Purchasing Organizations (GPOs), each focusing on high-demand sectors: NutraGPO™ : Nutraceuticals and wellness products. CBDGPO™ : Premium CBD and hemp products. SmokeGPO™ : Specialty vape and smoke retail products. MushroomGPO™ : Functional and adaptogenic mushrooms. SmartGPO™ : Tech-forward products for modern consumers. Financial Performance Q2 2023 Revenue : $1.21 million, a 25% increase from the previous quarter. Annual Revenue : $4.35 million, marking a 560% year-over-year growth . Investor Resources Investor Deck (PDF) Latest Earnings & Filings Ready to Invest? Join us in revolutionizing distribution and seizing opportunities in high-growth markets.   Invest in GPOX Today INVEST WITH US, WHERE OPPORTUNITY MEETS GROWTH Investors are Welcome INVEST IN YOUR FUTURE - CALL YOUR BROKER NOW Given these factors, investing in GPO PLUS might be a strategic move for those looking to be part of the next wave of technological innovation. DISCLAIMER Snapmediagroup.net  and Vanderbiltreport.com  are owned and operated by SMG a US based corporation. We have received compensation of up to $100,000 from KTM regarding the profiling of Spectral Capital Corp.  (OTCQB: GPOX) starting on April 15, 2025. It is important to note that we do not own any shares in GPOX: OTCQB.

Quantum BioPharma Ltd. (NASDAQ: QNTM) (CSE: QNTM) (FRA:0K91) is a biopharmaceutical company focused on developing innovative treatments for neurodegenerative and metabolic disorders, as well as alcohol misuse disorders. They are currently working on Lucid-MS, a compound that has shown promise in treating multiple sclerosis. They also developed unbuzzd™ and spun out an OTC version to Celly Nutrition Corp., in which Quantum BioPharma retains a 25.71% ownership stake. Upgrade your investments T he global hangover cure products market size was valued at USD 2.05 billion in 2022 and is expected to grow at a compound annual growth rate (CAGR) of 14.8% from 2023 to 2030 when it is expected to reach a value of USD C.2 billion. Until now, there is no effective product that  reverses  the effects of alcohol efficiently. Restores mental alertness and improves cognition post-alcohol consumption in an average of 15-30 minutes. Proprietary formulation of extracts, vitamins, and minerals helps with liver and brain function. Ingredients help reduce BAC faster than what the body would do naturally. You invested in a night out You invested in drinking You invested so much, you have a hangover Invest in Unbuzzd - Quantum BioPharma Ltd. (NASDAQ: QNTM) Where innovation meets returns, invest in QNTM Quantum Biopharma is known for its innovative approach in the biopharmaceutical sector, focusing on developing therapies that harness biological processes. Here are some potential business highlights for a company like Quantum Biopharma:   Innovative Therapies:  Developing cutting-edge biopharmaceuticals targeting unmet medical needs, particularly in areas like oncology, autoimmune diseases, or infectious diseases.   Strategic Partnerships: Collaborations with research institutions and pharmaceutical companies to enhance R&D capabilities and expedite the development process.    Intellectual Property:   Strong portfolio of patents that protects proprietary technologies and therapies, ensuring a competitive edge in the market.   Funding and Investment:   Securing significant funding from venture capital, grants , or partnerships that support ongoing research and development initiatives.   Regulatory Milestones:   Achieving key regulatory approvals that pave the way for market entry of new products.   Market Expansion:  Plans for global market entry or expansion into new therapeutic areas, broadening the potential customer base.   Expertise and Leadership:  A strong leadership team with deep expertise in biopharma, guiding the company through its growth phases.    These highlights would position Quantum Biopharma LTD as a forward-thinking player in the biopharmaceutical landscape. For the most accurate and detailed information, please refer to the company’s latest reports or press releases. Invest with QNTM, where opportunity meets growth Invest today – Enjoy tomorrow Call your Broker Now DISCLAIMER Snapmediagroup.net and Vanderbiltreport.com  are owned and operated by SMG a US-based corporation. We have received compensation of up to $100,000 from KTM regarding the profiling of Quantum BioPharma Ltd  (Nasdaq: QNTM)  starting on October 1, 2024. It is important to note that we do not own any shares in QNTM: NASDAQ .

NAPC Defense, Inc. (BLIS): Fully Licensed Veteran-Owned Leaders in Armament Sales and Production NAPC Defense, Inc. (formerly known as Treasure & Shipwreck Recovery, Inc.), trading as (OTCPK: BLIS), announces that it has completed the change of name with the State of Nevada and registration with the State of Florida, as well as a new website at www.NAPCDefense.com . It is also finalizing its application with FINRA to effect all additional merger terms announced in the March 27, 2024 press release. NAPC Defense, Inc. owns defense and construction contracting firm Native American Price Constructors, LLC.

Why Invest - The Founders Did!      $ 26.5 M invested by founders $12.6 M cash as of 3/31/24 $15 M capital raise in April 2024 Ramp up your Investments Citius Pharmaceuticals was incorporated? 2010 Citius Pharmaceuticals become a public company in September 2014      NOW IS THE TIME TO BUY Citius Pharmaceuticals, Inc. (Nasdaq: CTXR) is a late-stage biopharmaceutical company focused on the development and commercialization of first-in-class critical care products, with a pipeline of anti-invectives in adjunct cancer care, oncology, stem cell therapy and unique prescription products. LYMPHIR™ (denileukin diftitox-cxdl), our targeted immune therapy for adult patients with relapsed or refractory cutaneous T-cell lymphoma (CTCL) is now approved by the FDA. Commercialization efforts are underway to make this therapy available to patients.  INVEST IN YOUR FUTURE CALL YOUR BROKER NOW 1. Market Opportunity: Targeted Therapeutic Areas:  Citius Pharmaceuticals is involved in developing therapies for oncology, critical care, and other high-need areas. The market for innovative oncology treatments, for instance, is substantial, driven by the high prevalence of cancer and the demand for novel and effective treatments. Unmet Medical Needs:  The company's pipeline includes products aimed at addressing significant unmet medical needs. For example, if they are working on treatments for conditions with few existing options, this can present a lucrative opportunity. Regulatory Pathways:  Opportunities can also arise from favorable regulatory pathways. Accelerated approvals, orphan drug designations, or breakthrough therapy designations can significantly impact market potential. 2. Highlights: Pipeline and Products:   Has a diverse pipeline, including both clinical and preclinical stages. Products like Mino-Lok® (an antibiotic lock solution for treating infections in central venous catheters) and its investigational products are noteworthy. Partnerships and Collaborations:  Strategic alliances with larger pharmaceutical companies or research institutions can enhance Citius's capabilities and market reach. These collaborations can provide funding, resources, and expertise. Clinical Trial Progress:  Advancements in clinical trials, including positive Phase II or III results, can significantly boost the company's prospects and stock value. Keeping track of trial outcomes and timelines is crucial. Intellectual Property:  Strong intellectual property protection through patents can provide a competitive edge and ensure market exclusivity for its products. 3. Financial and Strategic Position: Funding and Investment:  Adequate funding from venture capital, public markets, or grants is essential for ongoing research and development. Citius's ability to attract investment can indicate confidence in its business model and prospects. Market Trends:  Staying attuned to market trends, such as advancements in biotechnology, regulatory changes, and shifts in healthcare policies, can also influence Citius’s opportunities and strategy. Secure your Investment Now   Unlock Your Rewards and Receive Medicus Tokens Join Vanderbiltreport.com Snapmediagroup.net and Vanderbiltreport.com are owned and operated by SMG a US-based corporation. We have received compensation of up to $100,000 from KTM regarding the profiling of Citius Pharmaceuticals, Inc. (Nasdaq: CTXR) starting on Sept 1, 2024. It is important to note that we do not own any shares in CTXR : NASDAQ.

Jeffrey Martin   ·  July 25, 2024 CD19-targeting CAR-T cells have recently shown incredible promise in the clinic for the treatment of autoreactive B cell-associated autoimmune diseases. However, the fact still remains that there are various biological characteristics of T cells that strain the therapeutic process in the form of toxicities, manufacturing difficulties, and high costs. Consequently, several biotech companies are now exploring the use of other cell types, mainly natural killer cells, as an alternative to T cells for autoimmunity, but does it make sense? In this article, I critically analyze the therapeutic potential of using NK cells to treat autoimmune diseases. Then, I evaluate the various biotech companies that are stepping into the ring to uncover the potential leaders poised to dominate the field. Success of T Cells Earlier this year, a  paper  was published in the New England Journal of Medicine that described the results of a clinical trial in which 15 patients with various autoimmune disorders (including systemic lupus erythematosus, idiopathic inflammatory myositis, and systemic sclerosis) were treated with CD19-targeting CAR-T cells. This trial marked the first time that CAR-T cells were administered to anyone other than a cancer patient, and the results were so incredible that they have sparked a paradigm shift in the field… Almost immediately upon infusion, the CAR-T cells rapidly expanded and effectively eliminated CD19+ B cells from peripheral blood within just 7 days. This was followed by a dramatic decline in autoantibody concentrations, which plummeted to near zero within 4 months. By 6 months, symptoms had all but disappeared, and remarkably, the vast majority of patients remained in remission and drug-free at the 2-year follow-up, regardless of their initial disease state – absolutely incredible. I think the final statement of the report truly captivates the significance of these findings: “Even though it is premature to judge whether these patients are indeed cured of their autoimmune disease, CD19 CAR T cells at least appear to be able to achieve sustained disease- and drug-free remission”. You don’t normally see a statement like this – one that suggests the discovery of a potential “cure” – in a scientific publication. An immune system “reset”? While the overall results are incredible – and I don’t mean to downplay them – the most interesting discovery to come out of this study was the fact that about 4 months after the initial CAR-T infusion, B cell populations began to re-emerge in the patients. The thing is, these new cells didn’t display any signs of autoreactivity and were instead predominantly naive, immature CD38+ B cells, newly differentiated from the bone marrow – very similar to what is seen in oncology. This finding led the researchers to propose that the cell therapy-mediated B cell depletion had effectively “reset” the patient’s immune system to a pre-autoreactive state ( Figure 1 A&B ). Figure 1. The concept of an immunological “reset” Figure 1. The concept of an immunological "reset" (read more) So, a single CAR-T infusion was able to effectively reset the patient’s immune system… This should rock your world if you’re a cell therapy company because this means that the administered cell therapy does not need to adopt long-term memory functionality to keep the autoimmune disease at bay, nor are subsequent infusions necessary; a single infusion of relatively short-lived cells seems to do the trick… In light of this, a question must be asked: is it necessary to use T cells or can a similar effect be attained with another cell type? Justifying the search for an alternative This question must be asked because while T cells are, no doubt, incredibly powerful effectors, there are several aspects of their biology that place a significant strain on the overall therapeutic process. I am thinking of two in particular: First, one of the main reasons that cell therapy for autoimmunity was not pursued earlier is because it was viewed as being too risky. The idea of introducing a highly immunogenic effector into an already hyper-stimulated immune environment seemed a bit like adding fuel to the fire. Although only mild toxicities were reported in this study, CAR-T-induced cytokine release syndrome (CRS) or off-target immune stimulation still pose serious risks and will continue to be of concern moving forward. Secondly, since T cells possess the ability to recognize foreign antigens, it is difficult to safely administer a donor-derived T cell therapy. As a result, most T cell therapies are either autologous, or require extensive genetic editing to remove TCR machinery. This complicates the manufacturing process resulting in inconsistent, and extremely expensive cell therapy products. While the risks and high costs of CAR-T cell therapy may be justified for cancer patients who may have no other option but to let the cancer kill them, the equation changes significantly for individuals suffering from autoimmune disorders. So, it is worth exploring alternative cell types with more controllable immunological activity that can be easily manufactured as ‘off-the-shelf’ products, such as natural killer (NK) cells. Making the Case for NK Cells NK Cell Basics Natural killer (NK) cells are a type of cytotoxic lymphocyte that play a vital role in the innate immune system. Equipped with a range of activating and inhibitory receptors, NK cells are capable of recognizing and destroying “stressed” or infected cells without the need for prior activation – they were literally born ready to kill. NKs also express high levels of Fc receptors (FcRs), which enable them to bind to the Fc portion of antibodies and subsequently engage and eliminate targets that are coated with antibodies. This unique feature, termed antibody-dependent cellular cytotoxicity (ADCC), is a sort of “antigen-dependent” targeting and will become particularly relevant later in our discussion. Crucially, unlike T cells, which recognize targets via MHC-antigen complexes, NK cells do not rely on MHC presentation to identify their targets. Instead, they use their surface receptors to detect changes in the expression of certain molecules on target cells, allowing them to rapidly respond to potential threats. This aspect of their biology is key as it allows the cells to be administered as an allogeneic cell therapy without the need for ANY genetic editing, making for highly convenient and cost-effective manufacturing of “off-the-shelf” cell therapies. Several NK cell therapy companies that have been exclusively focused on oncology are now seemingly beginning to do what so many CAR-T companies are doing: setting their sights onto autoimmunity. Figure 2. NK cells recognize targets in an antigen-independent manner Figure 2. NK cells recognize target in an antigen-independent manner Challenging T Cell Hegemony in Cell Therapy To continue this discussion, we must address the elephant in the room: if NK cells are so great, why do T cells dominate the cell therapy landscape? It is true that natural killer cells have long been overshadowed by T cells in the realm of cell therapy. However, this is mostly due to a handful of characteristics of NK cells that pose challenges in oncology. Mainly, i) their relatively short lifespan, ii) limited expansion upon target recognition, and iii) the requirement for higher cell numbers per infusion. However, in light of the results from the study mentioned above, these concerns may not pose as significant of a barrier in autoimmune diseases. For instance, the fact that long-term autoimmune remission does not require prolonged activity from the infused cells is a significant discovery. Remember, the newly emerged B cell population is non-pathological, and autoreactive B cell depletion can occur rapidly, often within just 7 days. This means that the therapeutic cells may not need to persist for an extended period of time. While it’s true that NK cells may not clear B cells as quickly as CAR-T cells, the key point is that we’re not talking about weeks or months of immune cell activity. In fact, a single infusion was enough to send most patients into remission for 2 years, highlighting the potential of a relatively short-lived cell, like NK cells, to provide long-term benefits in this setting. Also – and this is crucial – to achieve desirable therapeutic activity in oncology, a cell therapy must possess the ability to control the rapid proliferation of the cancerous cells. In this context, the limited expansion of NK cells upon target recognition may pose a bit of a barrier. However, in autoimmune diseases, the situation is different, as the number of autoreactive B cells is typically much lower, and rapid B cell proliferation is not a hallmark of these conditions. As a result, the lack of robust expansion exhibited by NK cells is likely not as significant a limitation in autoimmune diseases. This opens up an intriguing possibility: leveraging natural killer cells as an alternative to T cells for autoimmune disease treatment. With their unique characteristics and abilities, natural killer cells may prove to be as effective while also being significantly easier and cheaper to manufacture and administer. NK for Autoimmunity: Key Players As we’ve seen, the potential for cell therapies in autoimmunity is vast, and the use of NK cells may offer a superior approach to T cells. This belief is obviously not just held by me alone as there are several biotech companies in this space ( Table 1 ). Coeptis Therapeutics Coeptis is advancing a universal CAR-expressing effector cell therapy platform that can be targeted to precise antigens with modified antibodies. By administering SNAP-CAR-NK cells with an anti-CD19 antibody, Coeptis is able to target CD19+ B cells for the treatment of hematological malignancies and autoimmunity. The company sources its NK cells from umbilical cord blood-derived CD34+ stem cells (more on this later), which are then differentiated into natural killer cells. Nkarta Therapeutics Another company making waves in the field is Nkarta, which has developed a CD19-targeting CAR-NK cell platform called NKX019. Nkarta’s platform utilizes donor-derived peripheral blood-derived NK cells and has recently initiated a phase I clinical trial  for systemic lupus erythematosus (SLE). Artiva Biotherapeutics  Artiva has also made significant strides in the field, recently receiving a massive funding round to advance its AlloNK platform. This platform utilizes genetically unmodified umbilical cord-derived NK cells, which are used in combination with Rituximab (an anti-CD20 antibody) to target autoreactive B cells. Notably, Artiva’s platform is the only one that leverages the NK cell’s ability to engage in antibody-dependent cellular cytotoxicity (ADCC). They are currently recruiting for a phase I trial . Cytoimmune Therapeutics Cytoimmune has taken a unique approach to NK cell therapy, developing TRACK-NK cells that express PD-L1. These cells are derived from umbilical cord blood NK cells and are cultured to express PD-L1, which allows them to bind to PD-1 on hyperactive T and B cells and relieve the symptoms of autoimmunity. Notably, this is the only approach that can target both autoreactive B cells and T cells. FATE Therapeutics FATE, a company famous for its iPSC-derived cell therapies, is also developing a CD19-targeting iPSC-derived CAR-NK platform called FT522.  Century Therapeutics Similarly, Century Therapeutics is developing a CD19-targeting iPSC-derived CAR-NK platform, CTNY-101. Century is about to start recruiting for a phase I trial  using CTNY-101 for the treatment of Moderate to Severe Systemic Lupus Erythematosus Celularity Finally, Celularity, a company known for its placenta-derived cell therapies, is developing a placenta-derived CD19-targeting CAR-NK cell therapy that it plans to test in clinical trials for autoimmunity. The Verdict Okay, so what’s the verdict? Overall, I think success is going to come down to manufacturing, which will be heavily dependent on choice of cell source. I’m a firm believer that UCB-derived cells is the way to go (for several reasons). So, in my opinion, companies like Coeptis, Cytoimmune, and Artiva have the right idea in this regard. I am also a proponent of using genetically unmodified cells as this significantly streamlines the manufacturing and makes the overall process much more scalable – which is key to NK cell therapy because since the cells do not undergo robust expansion in the patient you need many more cells per infusion. Companies like Cytoimmune, Coeptis (they also have a genetically unmodified NK platform), and Artiva are leading the charge on this front. The biggest problem with this space right now is the complete lack of clinical data. We can speculate all we want and put on our “Molecular Immunologist” hats to make educated guesses, but the clinical data will be the ultimate judge. So, this is desperately needed and we should keep a close eye on the Artiva and Nkarta trials that are poised to initiate soon. Overall, I am very optimistic about the future of NK cell therapy and believe that, while the field is incredible young, there are big achievement in its future.