GLI1

WARRINGTON, Pa., April 08, 2024 (GLOBE NEWSWIRE) -- Windtree Therapeutics, Inc. (“Windtree” or the “Company”) (NasdaqCM: WINT), today announced that on April 2, 2024 the Company entered into an asset purchase agreement with Varian Biopharmaceuticals, Inc. (“Varian”) to acquire certain of its assets, including a proprietary atypical protein kinase C iota inhibitor (aPKCi). The Company also completed a $1.5 million convertible note bridge financing. The acquired Varian asset platform is a novel, potential high-potency, specific, aPKCi with possible broad use in oncology as well as certain rare malignant diseases. The asset platform includes two formulations: VAR-101 (topical) and VAR-102 (oral). In consideration of the purchase of the Varian assets, on April 2, 2024, the Company issued to certain of Varian’s creditor investors a total of 5,500 shares of Series B Convertible Preferred Stock, par value $0.001 per share (the “Preferred Shares”), that have an initial conversion price of $0.3603, which is subject to adjustment to no lower than $0.0721. Dividends on the Preferred Shares shall accrue at 10.0% per annum, subject to limited exceptions. With successful development, the Company would pay up to $2.3 million in milestone payments upon the achievement of certain regulatory and clinical development milestones relating to the acquired assets with the Company having the option to pay such milestone payments either in cash or the Company’s common stock. Protein kinase inhibitors are a class of anti-cancer therapeutics that have made a significant impact on the treatment of cancers. Among the kinase targets for further development are the Protein Kinase C (“PKC”) family, which are key components of many signaling pathways that drive the formation of cancer. aPKCi is a promising atypical PKC iota isozyme with defined oncogenic role in multiple signaling pathways, and in the initiation and development of multiple tumor types. GLI-1 is a transcription factor at the terminal end of the Hedgehog (Hh) signaling pathway, and many other important pathways, including RAS-RAF, TGFb, and P14K-AKT-mTOR. In many tumor types, high levels of GLI-1 expression is a negative prognostic marker. Pre-clinical data of the acquired platform showed dose dependent modulation of basal cell carcinoma cell viability and GLI-1 pathway modulation in vitro, as well as dose dependent anti-tumor activity in xenograft mouse models of non-small cell lung cancer and pancreatic ductal carcinoma. The protein kinase inhibitor adds to Windtree’s product candidate portfolio of novel pre-clinical and late-stage clinical product candidates and development programs, including SERCA2a activators and programs in out-licensed partnership. “Completion of the Varian asset acquisition and the bridge financing represents a potentially transformative next step for Windtree. Adding an innovative protein kinase inhibitor that has what we believe is an exciting pre-clinical data package with two formulations in development to our existing portfolio of product candidates creates an additional opportunity for value creation as we advance and look to partner our late and early-stage SERCA2a activator platform, including istaroxime,” said Craig Fraser, Chief Executive Officer of Windtree. “We see potential application in both rare and more prevalent tumor types, both in monotherapy and in combination with other agents. We believe there will be options for targeted disease selection and differentiation due to the potential for high specificity and topical formulation to treat various skin cancers. In the weeks to come, I look forward to providing updates on the use of this newly acquired capital and plans for our portfolio and programs, including licensing activity for istaroxime and our SERCA2a activators as well as our company strategy to have a stronger balance sheet and opportunities to further leverage our experience to grow the business.” In addition to the asset purchase, on April 2, 2024, the Company entered into a securities purchase agreement with certain investors whereby the Company agreed to sell to such investors $1.5 million in senior convertible notes (the “Notes”) for aggregate gross proceeds of $1.5 million (the “Notes Offering”). The Notes have an initial conversion price of $0.3603, which is subject to adjustment upon the occurrence of specified events to no lower than $0.0721 (subject to any stock split, stock dividend, stock combination, recapitalization or other similar transaction). The Company may, at its option, redeem the Notes subject to certain conditions and terms in the securities purchase agreement. The Notes may convert in a subsequent financing or will accrue interest at a rate of 10% per annum and mature on January 2, 2025, unless previously converted or redeemed. The Company intends to use the net proceeds from the Notes Offering for general corporate purposes. The Company agreed to seek stockholder approval for the issuance of all of the Company’s common stock issuable upon conversion of the Notes and the Preferred Shares in accordance with the rules and regulations of the Nasdaq Stock Market. Additional details are available by reading the Company’s Current Report on Form 8-K relating to the Varian asset acquisition and senior convertible note bridge financing, which was filed with the Securities and Exchange Commission on April 8, 2024. About Istaroxime Istaroxime is a first-in-class dual-mechanism therapy designed to improve both systolic and diastolic cardiac function. Istaroxime is a positive inotropic agent that increases myocardial contractility through inhibition of Na+/K+- ATPase with a complimentary mechanism that facilitates myocardial relaxation through activation of the SERCA2a calcium pump on the sarcoplasmic reticulum enhancing calcium reuptake from the cytoplasm. Data from multiple Phase 2 studies in patients with early cardiogenic shock or acute decompensated heart failure demonstrate that istaroxime infused intravenously significantly improves cardiac function and blood pressure without increasing heart rate or the incidence of cardiac rhythm disturbances. About Pure SERCA2a Activators These compounds activate SERCA2a and Windtree Therapeutics' research and development program is evaluating these preclinical product candidates, including oral and intravenous SERCA2a activator heart failure compounds. About Windtree Therapeutics, Inc. Windtree Therapeutics, Inc. is a biotechnology company focused on advancing early and late-stage innovative therapies for critical conditions and diseases. Windtree’s portfolio of product candidates includes istaroxime, a Phase II candidate with SERCA2a activating properties for acute heart failure and associated cardiogenic shock, pre-clinical SERCA2a activators for heart failure and VAR-101 and VAR-102, pre-clinical precision aPKCi inhibitors that are being developed for potential in rare and broad oncology applications. Windtree also has a licensing business model with partnership out-licenses currently in place. Forward Looking Statements This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. The Company may, in some cases, use terms such as "predicts," "believes," "potential," "proposed," "continue," "estimates," "anticipates," "expects," "plans," "intends," "may," "could," "might," "will," "should" or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such statements are based on information available to the Company as of the date of this press release and are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Company’s current expectations. Examples of such risks and uncertainties include: the Company’s ability to secure significant additional capital as and when needed; the Company’s ability to obtain approval for the issuance of all of the Company’s common stock issuable upon conversion of the Notes and the Preferred Shares; risks and uncertainties associated with the success and advancement of the clinical development programs for istaroxime and the Company’s other product candidates, including pre-clinical candidates such as VAR-101 and VAR-102; the Company’s ability to access the debt or equity markets; the Company’s ability to manage costs and execute on its operational and budget plans; the results, cost and timing of the Company’s clinical development programs, including any delays to such clinical trials relating to enrollment or site initiation; risks related to technology transfers to contract manufacturers and manufacturing development activities; delays encountered by the Company, contract manufacturers or suppliers in manufacturing drug products, drug substances, and other materials on a timely basis and in sufficient amounts; risks relating to rigorous regulatory requirements, including that: (i) the U.S. Food and Drug Administration or other regulatory authorities may not agree with the Company on matters raised during regulatory reviews, may require significant additional activities, or may not accept or may withhold or delay consideration of applications, or may not approve or may limit approval of the Company’s product candidates, and (ii) changes in the national or international political and regulatory environment may make it more difficult to gain regulatory approvals and risks related to the Company’s efforts to maintain and protect the patents and licenses related to its product candidates; risks that the Company may never realize the value of its intangible assets and have to incur future impairment charges; risks related to the size and growth potential of the markets for the Company’s product candidates, and the Company’s ability to service those markets; the Company’s ability to develop sales and marketing capabilities, whether alone or with potential future collaborators; the rate and degree of market acceptance of the Company’s product candidates, if approved; the economic and social consequences of the COVID-19 pandemic and the impacts of political unrest, including as a result of geopolitical tension, including the conflict between Russia and Ukraine, the People’s Republic of China and the Republic of China (Taiwan), and the evolving events in Israel and Gaza, and any sanctions, export controls or other restrictive actions that may be imposed by the United States and/or other countries which could have an adverse impact on the Company’s operations, including through disruption in supply chain or access to potential international clinical trial sites, and through disruption, instability and volatility in the global markets, which could have an adverse impact on the Company’s ability to access the capital markets. These and other risks are described in the Company’s periodic reports, including its Annual Report on Form 10-K, Quarterly Reports on Form 10-Q and Current Reports on Form 8-K, filed with or furnished to the Securities and Exchange Commission and available at www.sec.gov. Any forward-looking statements that the Company makes in this press release speak only as of the date of this press release. The Company assumes no obligation to update forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release. Contact Information:Eric Curtisecurtis@windtreetx.com

18 May 2023 BiodexaPharmaceuticalsEnters into Non-binding Letter of Intentfor Proposed Acquisition of Varian Biopharmaceuticals Biodexa Pharmaceuticals PLC (NASDAQ: BDRX) (“Biodexa” or the “Company”), a clinical stage biopharmaceutical company developing a pipeline of products aimed at primary and metastatic cancers of the brain is pleased to announce that it has signed non-binding letter of intent to potentially acquire Varian Biopharmaceuticals, Inc. (“VarianBio”), a private US precision oncology company developing novel therapeutics for the treatment of cancer. Background to the proposed acquisition In recent communications, the Company has referenced a shift in strategy from a drug delivery company to a therapeutics company. Currently, the Company’s only clinical asset is MTX110 which is being developed for three intractable rare and orphan brain cancers. The Company’s intention is to add to, and diversify, its development pipeline with a continued focus on rare and orphan products and/or oncology therapeutics and VarianBio represents the first of such opportunity. Information on VarianBio VarianBio is developing a high-potency, specific atypical protein kinase C iota (“aPKCi”) inhibitor with best-in-class potential as a treatment for various oncology indications with an initial focus on basal cell carcinoma (BCC) and molecularly targeted solid tumors. VarianBio’s rationally designed aPKCi small molecule inhibitor candidate that has been optimized for potency, selectivity and tolerability. aPKCi has been implicated as an oncogene in a number of human cancers, including BCC, cutaneous T-cell lymphoma (CTCL), non-small cell lung cancer (NSCLC), acute myeloid leukemia (AML), colorectal cancer, and pancreatic cancer, among others. aPKCi has also been demonstrated to have a role in allowing the immune system to recognize tumors, recruit immune cells into the area, and ramp up the anti-tumor response to kill cancer cells in the lab by shrinking their tumors. The active pharmaceutical ingredient in VAR-101/102, a novel aPKCi inhibitor, has demonstrated dose dependent anti-tumor activity in murine and human BCC cell lines, as well as other cancer models. VAR-101 will be developed in a topical formulation for BCC which has the potential to offer optimal clinical utility as a surgical neoadjuvant or adjuvant therapy. Following completion of IND-enabling skin toxicology studies, VAR-101 is targeting to start a Phase I proof-of-concept study in the first quarter of 2024. VAR-102, an oral formulation of the active aPKCi inhibitor, lends itself to broader applications in multiple tumor types. The Company believes that VAR-101 and VAR-102, if approved, could represent significant medical and commercial opportunities. Terms of the proposed acquisition Under the non-binding letter of intent, VarianBio will merge into an acquisition subsidiary of the Company and it is proposed that VarianBio equity and debt holders (together,“VarianBio Securityholders”) will receive 10MM of the Company’s American Depositary Shares (“ADSs”), at close as initial consideration. On a pro forma basis, prior to the planned financing discussed below, VarianBio Securityholders will own approximately 34% of the post-acquisition Company. VarianBio Securityholders will receive up to a further 6MM ADSs, issuable in two phases: 3MM upon the commencement of the first pivotal registration study of a VarianBio product and an additional 3MM upon the first FDA approval of a VarianBio product. In addition, pursuant to the non-binding heads of terms, the Company plans to raise not less than US$7.0MM, net of expenses, which will be used to fund VAR-101 through its Phase I proof-of-concept study that VAR-101 is targeting to commence in the first quarter of 2024. The acquisition agreement is also expected to contain other customary conditions, including shareholder approval, and appropriate representations and warranties by the parties. For more information, please contact: Biodexa Pharmaceuticals PLC Stephen Stamp, CEO and CFO Tel: +44 29 20480 180 Varian Biopharmaceuticals, Inc. Jeffrey Davis, CEO Tel: +1 239-302-1644 Edison Group (Investor Relations) Alyssa Factor Tel: +1 (860) 573 9637 Email: afactor@edisongroup.com About Biodexa Pharmaceuticals PLC Biodexa Pharmaceuticals PLC (listed on NASDAQ: BDRX) is a clinical stage biopharmaceutical company developing a pipeline of products aimed at primary and metastatic cancers of the brain. The Company’s lead candidate, MTX110, is being studied in aggressive rare/orphan brain cancer indications including recurrent glioblastoma and diffuse midline glioma. MTX110 is a liquid formulation of the histone deacetylase (HDAC) inhibitor, panobinostat. This proprietary formulation enables delivery of the product via convection-enhanced delivery (CED) at potentially chemotherapeutic doses directly to the site of the tumour, by-passing the blood-brain barrier and avoiding systemic toxicity. Biodexa is supported by three proprietary drug delivery technologies focused on improving the bio-delivery and bio-distribution of medicines. Biodexa’s headquarters and R&D facility is in Cardiff, UK. For more information visit About Varian Biopharmaceuticals, Inc. Varian Biopharmaceuticals, Inc. (“VarianBio”) is private precision oncology company developing novel therapeutics for the treatment of cancer. Precision oncology, whereby physicians use DNA testing to look for genetic mutations of the unique tumors, holds the promise of more targeted treatment recommendations with therapies designed to fight specific tumor types. A recently published global Precision Oncology Market analysis by Reports and Data found the global precision oncology market size amounted to US$49.9 billion in 2019 and is expected to grow at a CAGR of 99% over the next eight years to reach US$99.7 billion in 2027. VarianBio is developing a best-in-class high-potency, specific atypical protein kinase C iota (“aPKCi”) inhibitor for the treatment of various tumor types in multiple formulations. Recent scientific publications have characterized aPKCi as an oncogene whose activity may play a fundamental role in the regulation of cancer-associated transcription factors including GLI-1 and K-RAS. VarianBio’s lead drug candidate, VAR-101, is being developed in a topical formulation for the treatment of basal cell carcinoma. VAR-102, an oral formulation, is being developed for the treatment of a wide variety of solid tumors where studies have shown potent aPKCi inhibition would be impactful, including non-small cell lung cancer (NSCLC), pancreatic cancer and colorectal cancer. For more information on Varian Biopharmaceuticals, Inc., visit Forward-Looking Statements Certain statements in this announcement may constitute "forward-looking statements" within the meaning of legislation in the United Kingdom and/or United States. Such statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and are based on management's belief or interpretation. All statements contained in this announcement that do not relate to matters of historical fact should be considered forward-looking statements. Reference should be made to those documents that Biodexa shall time to time or announcements that may be made by Biodexa in accordance with the rules and regulations promulgated by the US Securities and Exchange Commission, which contains and identifies other important factors that could cause actual results to differ materially from those contained in any projections or forward-looking statements. These forward-looking statements speak only as of the date of this announcement. All subsequent written and oral forward-looking statements by or concerning Biodexa or VarianBio are expressly qualified in their entirety by the cautionary statements above. Except as may be required under relevant laws in the United States, Biodexa does not undertake any obligation to publicly update or revise any forward-looking statements because of new information, future events or otherwise arising. No Offer or Solicitation This announcement or any part of it is for information purposes only and is not intended to and it does not constitute an offer to sell or issue or the solicitation of an offer to subscribe for or buy or an invitation to subscribe for or purchase any securities or the solicitation of any vote or approval in respect of such actions in any jurisdiction, nor shall there be any sale, issuance or transfer of securities in any jurisdiction in contravention of applicable law. Important Notices This announcement does not constitute a recommendation concerning any investor’s investment decision with respect to the Company’s securities. Any indication in this announcement of the price at which ordinary shares or ADSs have been bought or sold in the past cannot be relied upon as a guide to future performance. The price of shares and any income expected from them may go down as well as up and investors may not get back the full amount invested upon disposal of the shares. Past performance is no guide to future performance. This announcement does not identify or suggest, or purport to identify or suggest, the risks (direct or indirect) that may be associated with an investment in the Company’s securities. The contents of this announcement are not to be construed as legal, business, financial or tax advice. Each investor or prospective investor should consult their or its own legal adviser, business adviser, financial adviser or tax adviser for legal, financial, business or tax advice. Persons (including, without limitation, nominees and trustees) who have a contractual or other legal obligation to forward a copy of this announcement should seek appropriate advice before taking any action. Neither the content of the Company’s website (or any other website) nor the content of any website accessible from hyperlinks on the Company’s website (or any other website) is incorporated into or forms part of this announcement.

Chronic diseases often lead to fibrosis, a condition in which organ tissue suffers from excessive scarring. Researchers have now developed an immunotherapy that specifically targets the cause -- activated fibroblasts -- while leaving normal connective tissue cells unharmed. If this approach is also found to work in humans, it could lead to an effective treatment for fibrosis. Fibrosis is a pathological proliferation of connective tissue that destroys the organ tissue. It is the ultimate consequence of almost every kind of chronic damage. Fibrosis can occur in almost every type of tissue in the body, although the liver, lungs, heart and kidneys are most often affected. Fibrosis is responsible for up to 45 percent of all mortality in industrialized countries. Inflammation or vascular disorders often cause chronic organ damage. They activate the fibroblasts, which then begin to proliferate uncontrollably and create deposits of fibrous tissue. This scars the organ tissue, destroying it little by little. The functioning of the affected organ worsens noticeably until it fails completely. Eliminating activated fibroblasts while leaving resting cells undamaged An international research team led by the University of Zurich (UZH) has now developed a new strategy to eliminate fibroblasts in a targeted manner. "In animals, we were able to trigger an immune response similar to that to a vaccination, in which the activated connective tissue cells were destroyed while the resting fibroblasts were left unharmed," explains study leader Professor Christian Stockmann of the Institute of Anatomy at the University of Zurich. In this manner, researchers were able to reduce fibrosis in vital organs such as liver and lungs while at the same time leaving healthy tissue unharmed. Difference in surface structures identified This is where previous strategies for fibrosis treatment had previously failed, since they also damaged resting fibroblasts. Resting fibroblasts are important, however, for maintaining the structure and functioning of healthy tissue. Researchers therefore studied the differences between the surfaces of resting and of activated connective tissue cells. "Our computer-assisted analyses revealed that fragments of two surface proteins -- Adam12 and Gli1 -- which can be detected by the immune system, are present in large numbers on activated fibroblasts, while there are very few on the resting cells," explains Stockmann. The activity of these two protein genes is stimulated by chronic tissue damage, which means the activated fibroblasts produce the said proteins in larger quantities. Immunotherapy reduces lung and liver fibrosis in mice The researchers then used these two surface structures as a vaccine in mice in order to trigger an immune response via cytotoxic T-cells. These immune cells normally eliminate virus-infected or cancerous cells. "With the newly developed immunotherapy, we were able to eliminate fibroblasts efficiently in mice, thus reducing fibrosis in the liver and the lungs, without affecting healthy organ tissue," says Stockmann. If scientists manage to successfully trigger a comparable, targeted immune response in humans, then vaccine-based immunotherapy could be used in future for the treatment of patients with organ fibrosis.