Chronic lung disease

Johnson & Johnson is a partner on Contineum Therapeutics’ most advanced program, which is currently in mid-stage clinical testing for multiple sclerosis. As that research continues and Contineum plans to advance the development of its wholly owned assets, the biotech is moving forward with plans for an IPO. Contineum, which traces its origins to a startup creation engine of venture capital firm Versant Ventures, filed its IPO paperwork with the Securities and Exchange Commission late Friday. The company has not yet set any financial terms for its planned stock market debut, but IPO research firm Renaissance Capital said the offering could reach up to $150 million. The San Diego-based biotech has applied for a Nasdaq listing under the stock symbol “CTNM.” Contineum’s most advanced program is PIPE-307, a small molecule designed to selectively block the M1R receptor. This approach has potential applications in the treatment of multiple sclerosis and depression. Contineum has reported Phase 1 results showed the drug candidate was well tolerated across all doses and showed no dose-related effects on cognitive function. Nearly a year ago, J&J licensed global rights to PIPE-307 for all potential indications. However, the deal still permits Contineum to develop this molecule for relapsing and remitting forms of MS by conducting a Phase 2 study. That clinical trial is ongoing. A Phase 1 test of this molecule in depression is also underway as part of the J&J collaboration. The lead wholly owned Contineum asset is PIPE-791, a program currently in Phase 1 testing. This small molecule is designed to block LPA1, a receptor whose activation is associated with the development of organ scarring called fibrosis. The company believes the molecule’s ability to block LPA1 could treat idiopathic pulmonary fibrosis (IPF), a chronic lung disorder with few available treatments. MS is another potential application for PIPE-791. Levels of LPA, a pro-inflammatory protein, are elevated in the blood and cerebrospinal fluid of MS patients, which may contribute to the progression of this disease, Contineum said in the filing. One key feature of this molecule is its ability to penetrate the brain. In preclinical research, the company said blocking the LPA1 receptor reduces neuroinflammation and promotes remyelination, the formation of new myelin sheaths on axons that have lost this protective layer. Contineum plans to submit an application this year seeking permission in the U.K. for an open-label Phase 1b test of PIPE-791 to assess the molecule’s ability to bind to receptors in the lungs and brain as measured by PET imaging. This study will inform dose selection for planned future Phase 2 tests of the molecule in IPF and progressive MS. The pipeline also includes CTX-343, an LPA1 receptor-blocking molecule that does not cross the blood brain barrier. This capability could provide Contineum more options for its drug portfolio, the company said. CTX-343 is currently preclinical. Contineum traces its roots to Inception Sciences, one of the drug discovery engine of Versant Ventures. Inception and Roche had collaborated to discover and develop small molecules that promote remyelination of nerve fibers damaged as MS progresses. After Roche acquired this neuroscience program for an undisclosed sum in 2018, Versant launched Pipeline Therapeutics, a startup led by the same team that worked on the program that Roche acquired. Versant said Pipeline would focus on developing “next-generation neurodegenerative therapies.” In late 2023, Pipeline changed its name to Contineum Therapeutics. Contineum has raised about $194 million in financing, according to the filing. The J&J alliance paid $50 million upfront and could pay out up to $1 billion tied to the achievement of milestones. Versant is Contineum’s largest shareholder with a 32.2% pre-IPO stake; Johnson & Johnson’s stake is 10.1%. The company’s most recent financing was a 2021 Series C round that raised $80 million. As of the end of 2023, Contineum reported a $15.5 million cash position along with $109.6 million in marketable securities. That capital, combined with the IPO proceeds, will go toward continued clinical development of the LPA1 receptor antagonist, including the completion of Phase 1b testing. An unspecified amount of additional cash will go toward planned Phase 2 tests in IPF and progressive MS. Contineum also plans to use the IPO proceeds to complete Phase 2 testing of its J&J-partnered molecule in relapsing and remitting forms of MS. Image: Getty Images

Company advancing an innovative pipeline of NKT cell modulators for the treatment of inflammatory, fibrotic and autoimmune diseases Ongoing efforts to build a robust global patent estate for a growing pipeline targeting high-value indications in need of innovation LA JOLLA, CA, March 14, 2024 (GLOBE NEWSWIRE) -- GRI Bio, Inc. (NASDAQ: GRI) (“GRI Bio” or the “Company”), a biotechnology company advancing an innovative pipeline of Natural Killer T (NKT) cell modulators for the treatment of inflammatory, fibrotic and autoimmune diseases, today announced that the Canadian Intellectual Property Office (CIPO) has issued a notice of allowance for Patent Application No. 3,007,970 titled, "Prevention and Treatment of Inflammatory Conditions." A patent from the recently allowed application is expected to be issued in the coming months. When issued, the patent will cover claims including compositions and methods for modulating type 2 and/or type 1 invariant NKT (iNKT) cells in the prevention and treatment of inflammatory conditions of the liver. More specifically, when issued the patent will cover the prevention and treatment of inflammatory and fibrotic conditions through the administration of a Retinoic Acid Receptor (RAR) agonist that inhibits iNKT cells and the administration of an RAR agonist that inhibits the activity of iNKT cells in a subject. “We have remained committed to bolstering our intellectual property protection across our innovative pipeline of NKT cell modulators. We are pleased to receive this notice of allowance for our Canadian patent and believe this further validates our differentiated approach to the prevention and treatment of inflammatory, fibrotic and autoimmune diseases as well as underscores the global unmet need amongst patients. Our team is focused on driving our development programs forward, generating a growing body of data and continuing to build our patent estate with the ultimate goal of bringing to market much needed treatment options,” Marc Hertz, PhD, Chief Executive Officer of GRI Bio. GRI Bio is currently advancing its lead program GRI-0621, a small molecule RAR-βɣ dual agonist candidate that inhibits the activity of human iNKT cells, in a Phase 2a, randomized, double-blind, multi-center, placebo-controlled, parallel-design, 2-arm study for the treatment of Idiopathic Pulmonary Fibrosis (IPF). IPF is a rare chronic progressive pulmonary disease with abnormal scarring of the lung blocking the movement of oxygen into the bloodstream. Interim data from the Phase 2a biomarker study is expected in the first half of 2024 and topline results are expected in the second half of 2024. For more information about the Company’s innovative pipeline of NKT cell regulators for the treatment of inflammatory, fibrotic and autoimmune diseases, visit gribio.com. About GRI Bio, Inc. GRI Bio is a clinical-stage biopharmaceutical company focused on fundamentally changing the way inflammatory, fibrotic and autoimmune diseases are treated. GRI Bio’s therapies are designed to target the activity of NKT cells, which are key regulators earlier in the inflammatory cascade, to interrupt disease progression and restore the immune system to homeostasis. NKT cells are innate-like T cells that share properties of both NK and T cells and are a functional link between the innate and adaptive immune responses. iNKT cells play a critical role in propagating the injury, inflammatory response, and fibrosis observed in inflammatory and fibrotic indications. GRI Bio’s lead program, GRI-0621, is an inhibitor of iNKT cell activity and is being developed as a novel oral therapeutic for the treatment of idiopathic pulmonary fibrosis, a serious disease with significant unmet need. The Company is also developing a pipeline of novel type 2 NKT agonists for the treatment of systemic lupus erythematosus. Additionally, with a library of over 500 proprietary compounds, GRI Bio has the ability to fuel a growing pipeline. Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements may be identified by the use of words such as “anticipate,” “believe,” “contemplate,” “could,” “estimate,” “expect,” “intend,” “seek,” “may,” “might,” “plan,” “potential,” “predict,” “project,” “target,” “aim,” “should,” “will,” “would,” or the negative of these words or other similar expressions. These forward-looking statements are based on the Company’s current beliefs and expectations. Forward-looking statements include, but are not limited to, statements regarding: the Company’s expectations with respect to development and commercialization of the Company’s product candidates, the timing of initiation or completion of clinical trials and availability of resulting data, the potential benefits and impact of the Company’s clinical trials and product candidates and any implication that the data or results observed in preclinical trials or earlier studies or trials will be indicative of results of later studies or clinical trials, the Company’s beliefs and expectations regarding and the potential of the Company’s product candidates to meet unmet treatment needs and improve patient quality of life, the Company’s beliefs and expectations about the timing, outcome and robustness of the Company’s patent applications and potential intellectual property protections. Actual results may differ from the forward-looking statements expressed by the Company in this press release and consequently, you should not rely on these forward-looking statements as predictions of future events. These forward-looking statements are subject to inherent uncertainties, risks and assumptions that are difficult to predict, including, without limitation: (1) the Company’s inability to maintain the listing of the Company’s common stock on Nasdaq and to comply with applicable listing requirements; (2) changes in applicable laws or regulations; (3) the inability of the Company to raise financing in the future; (4) the success, cost and timing of the Company’s product development activities; (5) the inability of the Company to obtain and maintain regulatory clearance or approval for its respective products, and any related restrictions and limitations of any cleared or approved product; (6) the inability of the Company to identify, in-license or acquire additional technology; (7) the inability of the Company to compete with other companies currently marketing or engaged in the development of products and services that the Company is currently developing; (8) the size and growth potential of the markets for the Company’s products and services, and their respective ability to serve those markets, either alone or in partnership with others; (9) the failure to achieve any milestones or receive any milestone payments under any agreements; (10) inaccuracy in the Company’s estimates regarding expenses, future revenue, capital requirements and needs for and the ability to obtain additional financing; (11) the Company’s ability to protect and enforce its intellectual property portfolio, including any newly issued patents; and (12) other risks and uncertainties indicated from time to time in the Company’s filings with the U.S. Securities and Exchange Commission (the “SEC”), including the risks and uncertainties described in the “Risk Factors” section of the Company’s most recent Annual Report on Form 10-K filed with the SEC on February 24, 2023 and subsequently filed reports, including our Quarterly Report on Form 10-Q filed with the SEC on May 15, 2023 and our Quarterly Report on Form 10-Q filed with the SEC on November 14, 2023. Forward-looking statements contained in this announcement are made as of this date, and the Company undertakes no duty to update such information except as required under applicable law. Investor Contact: JTC Team, LLC Jenene Thomas (833) 475-8247 GRI@jtcir.com

Post-meal hyperglycemia was significantly reduced by 20% with inhaled insulin compared with rapid-acting insulin delivered through MDI or insulin pumps Subjects utilizing inhaled insulin experienced a 22% decrease in mean glucose excursions in the first two hours compared to the standard of care 17-week primary endpoint results will be presented during a 90-minute symposium at the American Diabetes Association’s Scientific Sessions in June DANBURY, Conn. and WESTLAKE VILLAGE, Calif., March 11, 2024 (GLOBE NEWSWIRE) -- MannKind Corporation (Nasdaq: MNKD), a company focused on the development and commercialization of inhaled therapeutic products and devices for patients with endocrine and orphan lung diseases, announced initial meal challenge data from INHALE-3 that was presented by Dr. Irl B. Hirsch at the 17th International Conference on Advanced Technologies and Treatments for Diabetes (ATTD) in Florence on March 8th. INHALE-3 is a Phase 4 U.S. clinical trial evaluating inhaled insulin (plus basal) vs. standard of care. The statistically significant findings included: Subjects utilizing inhaled insulin experienced significantly reduced post-meal hyperglycemia, compared with those who used subcutaneous rapid-acting analogues (RAA) delivered by MDI or pumps Area under the curve (AUC; 180 mg/dL) was reduced by 20% Inhaled insulin subjects demonstrated significantly lower glucose excursions from baseline Mean glucose excursions were reduced by 22% In the inhaled insulin group, mean glucose levels peaked 15 minutes sooner than in the standard of care group despite inhaled insulin being given at start of the meal vs. RAA being administered 5-15 minutes prior to the meal “Clinician have been seeking options for people living with diabetes in hopes of identifying treatments that provide improved mealtime control,” said Dr. Hirsch, Professor of Medicine and Diabetes Treatment and Teaching Chair at the University of Washington and the INHALE-3 Study Protocol Chair. “It is exciting to share data from this study’s standardized meal challenge, demonstrating inhaled insulin can help address this unmet need.” The 17-week endpoint results from INHALE-3 will be presented Saturday, June 22, during a symposium at the American Diabetes Association’s 84th Scientific Sessions in Orlando. “One of the challenges of inhaled insulin adoption has been under-dosing when converting from injectable insulin, which causes patients to experience hyperglycemia,” said Dr. Kevin Kaiserman, Senior Vice President, Clinical Development and Medical Affairs for MannKind Corporation. “In this large, randomized trial utilizing more appropriate dose conversion, we are excited to see meal challenge results support the safety and efficacy of inhaled insulin from the start.” INHALE-3 is a 17-week randomized controlled trial with a 13-week extension. The study, which enrolled 141 patients (123 randomized), assigned participants over 18 years of age with T1D who are using MDI, an automated insulin delivery system, or a pump without automation to either continue their standard of care or initiate an insulin regimen of a daily basal injection plus Afrezza for boluses (mealtime and corrections). Subjects utilizing inhaled insulin received a higher initial conversion dose than in the current label. Both arms utilized continuous glucose monitoring to assess glucose control. A1c levels were obtained at baseline, 17 and 30-weeks. For the meal challenge, the inhaled insulin group took an inhaled insulin dose immediately prior to a standardized meal (a 240 calorie nutritional shake) whereas those using usual care used RAA 5-15 minutes prior to the meal. More information on the INHALE-3 study is available at: ClinicalTrials.gov(NCT05904743). About Afrezza Afrezza (insulin human) Inhalation Powder is a rapid-acting inhaled human insulin indicated to improve glycemic control in adults with diabetes mellitus. Limitations of Use: Not recommended for the treatment of diabetic ketoacidosis or in patients that smoke or have recently stopped smoking. Important Safety Information WARNING: RISK OF ACUTE BRONCHOSPASM IN PATIENTS WITH CHRONIC LUNG DISEASE • Acute bronchospasm has been observed in Afrezza-treated patients with asthma and COPD • Afrezza is contraindicated in patients with chronic lung disease such as asthma or COPD • Before initiating Afrezza, perform a detailed medical history, physical examination, and spirometry (FEV1) to identify potential lung disease in all patients. Most common adverse reactions are hypoglycemia, cough, and throat pain or irritation. Please see additional Important Safety Information, Full Prescribing Information, including BOXED WARNING, available on Afrezza.com/safety. About MannKind MannKind Corporation (Nasdaq: MNKD) focuses on the development and commercialization of innovative therapeutic products and devices to address serious unmet medical needs for those living with endocrine and orphan lung diseases. We are committed to using our formulation capabilities and device engineering prowess to lessen the burden of diseases such as diabetes, pulmonary arterial hypertension (PAH) and nontuberculous mycobacterial (NTM) lung disease. Our signature technologies – dry-powder formulations and inhalation devices – offer rapid and convenient delivery of medicines to the deep lung where they can exert an effect locally or enter the systemic circulation. With a passionate team of Mannitarians collaborating nationwide, we are on a mission to give people control of their health and the freedom to live life. Please visit mannkindcorp.com to learn more, and follow us on LinkedIn, Facebook, Twitter or Instagram. Forward-Looking Statements This press release contains forward-looking statements about the planned release of results from an ongoing clinical study that involves risks and uncertainties. Words such as “believes”, “anticipates”, “plans”, “expects”, “intends”, “will”, “goal”, “potential” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon MannKind’s current expectations. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, the risk that we may not achieve our projected development goals in the timeframes we expect, as well as other risks detailed in MannKind’s filings with the Securities and Exchange Commission, including its Annual Report on Form 10-K for the year ended December 31, 2023, and subsequent periodic reports on Form 10-Q and current reports on Form 8-K. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. All forward-looking statements are qualified in their entirety by this cautionary statement, and MannKind undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this press release. AFREZZA and MANNKIND are registered trademarks of MannKind Corporation. For MannKind: Christie Iacangelo, Corporate Communications (818) 292-3500 Email: media@mannkindcorp.com Rose Alinaya, Investor Relations (818) 661-5000 Email: ir@mannkindcorp.com