Bloom Syndrome

Low-dose LTI-03 (2.5 mg BID), a Caveolin-1 related peptide, reduced expression of multiple profibrotic proteins in both pathological basal-like cells and fibroblasts and increased the expression of a biomarker indicative of epithelial health, suggesting potential therapeutic effect Positive trend was observed in seven of eight IPF biomarkers evaluated Low-dose LTI-03 was well-tolerated, with no safety signal observed Data from Cohort 2 evaluating high-dose LTI-03 (5 mg BID) is expected in the third quarter of 2024 Company to host conference call on Wednesday, May 1st at 9:00 am ET WALTHAM, Mass., May 01, 2024 (GLOBE NEWSWIRE) -- Aileron Therapeutics, Inc. (“Aileron”) (NASDAQ: ALRN), a biopharmaceutical company advancing a novel pipeline of first-in-class medicines to address significant unmet medical needs in orphan pulmonary and fibrosis indications, today announced positive data from Cohort 1 of the ongoing Phase 1b clinical trial evaluating the safety and tolerability of inhaled LTI-03 in patients diagnosed with idiopathic pulmonary fibrosis (IPF). LTI-03 is a novel, Caveolin-1-related peptide that addresses both inhibition of pro-fibrotic signaling and survival of critical epithelial cells. Following inhaled administration of low dose LTI-03 (2.5 mg BID), a positive trend was observed in seven out of eight biomarkers with evidence of reduced expression among profibrotic proteins produced by basal-like cells and fibroblasts that contribute to the progression of IPF, including data from several biomarkers that were statistically significant, reinforcing the potential of LTI-03 to improve lung function and reverse the course of IPF. “We find it encouraging that low dose LTI-03 achieved statistical significance in three out of eight biomarkers evaluated in the trial” said Brian Windsor, Ph.D., President and Chief Executive Officer of Aileron. “This, paired with the positive trends observed in several of the other biomarkers, strengthens our belief that LTI-03 has the potential for disease stabilization or even reversal. We look forward to continuing to evaluate LTI-03 in the ongoing Phase 1b study and sharing results from the high-dose cohort later this year.” Summary of Cohort 1 Analysis Twelve patients were enrolled in Cohort 1 of the ongoing Phase 1b clinical trial, three in the placebo arm and nine in the active arm. Patients had a bronchoscopy at baseline, received a low dose of LTI-03 (2.5mg BID) twice a day for 14 days, followed by a bronchoscopy on day 14 and seven days of follow-up. Cohort 1 findings include: Reduced expression of multiple profibrotic proteins in both pathologic basal-like cells and fibroblasts, with statistically significant decreases observed in GAL-7, TSLP and Col-1α1 biomarkers, supporting the potential of LTI-03 to reduce fibrosis, inflammation and associated changes in the lung. Stimulated production of solRAGE, a factor indicative of type I epithelial cell health that is a critically important aspect of IPF and has gone largely unaddressed. LTI-03 did not induce inflammation in peripheral blood mononuclear cells (PBMCs). Results show LTI-03 to be generally well-tolerated with no serious adverse events (SAEs) reported. The Phase 1b study is ongoing, with topline results from the high-dose cohort expected in the third quarter of 2024. “We are pleased with the Cohort 1 data as it seems to confirm LTI-03’s mode of action in patients with IPF” said Andreas Gunther, M.D., Head of the Center for Interstitial and Rare Lung Diseases of the Justus Liebig University in Giessen, Germany. “Importantly, the statistical significance observed in collagen deposition, inflammation and cellular processes underscores the potential of LTI-03 to act on both, fibroblasts as well as epithelial cells, the latter of which are believed to be causative in onset and aggravation of the disease. These findings underscore the promise of LTI-03 to combat the devastating effects of IPF and improve lung function and quality of life for those living with the disease. I look forward to further evaluating LTI-03’s potential, particularly at the higher dose, in the ongoing study.” Conference Call Information Aileron will host a conference call on Wednesday, May 1st at 9:00am ET to discuss the initial results from Cohort 1 of the Phase 1b clinical trial of LTI-03 in IPF. To access the call, please dial +1 646-876-9923 (domestic) or +44 330 088 5830 (international) and reference meeting ID: 970 4548 0706 when prompted by the operator. A live webcast of the event can be accessed at . A replay of the webcast will be available following the completion of the event. About the Phase 1 Clinical Trial of LTI-03 The Phase 1b clinical trial of LTI-03 is a randomized, double-blind, placebo controlled, multi-center, dose escalation study in patients recently diagnosed with IPF that have not received prior treatment with anti-fibrotic agents for at least two months (NCT05954988). Eligible patients are randomly assigned (3:1) to receive one of two doses of LTI-03 or placebo. The primary objective of the study is to investigate the safety and tolerability of LTI-03 in patients with IPF after treatment for 14 consecutive days, with multiple biomarker concentration as exploratory endpoints. About IPF IPF is a chronic lung disease characterized by progressive tissue scarring that prevents proper lung function. It is a progressive, fatal, age-associated lung disease affecting approximately 100,000 people in the United States1. IPF typically presents in adults 65 or older and is usually fatal within two to five years after diagnosis2. About LTI-03 and Caveolin-1 (Cav1) LTI-03 is a seven amino acid peptide, the sequence of which is derived from the caveolin scaffolding domain (CSD), an important binding region of the Cav1 protein. Cav1 normally serves a critical function in the prevention of fibrosis by maintaining a balance between pathways that both initiate and arrest lung repair and cell movement. Through the CSD, caveolin interacts with a large number of signaling molecules, all of which possess a caveolin binding domain region. Cav1 expression is decreased in IPF lung tissues and has been demonstrated to decrease during the fibrotic phase of bleomycin, or BLM, lung injury in mice. Restoring the balance of important biological signals in the lung may not only slow lung function decline but could also restore healthy lung function through the protection of healthy epithelial cells. About Aileron Therapeutics Aileron Therapeutics is a biopharmaceutical company advancing a novel pipeline of first-in-class medicines to address significant unmet medical needs in orphan pulmonary and fibrosis indications. Aileron’s lead product candidate, LTI-03, is a novel, synthetic peptide with a dual mechanism targeting alveolar epithelial cell survival as well as inhibition of profibrotic signaling. Currently, LTI-03 is being evaluated in a Phase 1b clinical trial for the treatment of idiopathic pulmonary fibrosis, with Cohort 2 results expected to be reported in the third quarter this year. Aileron’s second product candidate, LTI-01, is a proenzyme that has completed Phase 1b and Phase 2a clinical trials for the treatment of loculated pleural effusions. LTI-01 has received Orphan Drug Designation in the US and EU and Fast Track Designation in the US. References 1 Pergolizzi, Jr., J., LeQuang, J., Varrassi, M., Breve, F., Magnusson, P., Varrassi, G., (2023). What Do We Need to Know About Rising Rates of Idiopathic Pulmonary Fibrosis? A Narrative Review and Update. Springer Nature, Published online 2023 Jan 24. Doi: 10.1007/s12325-022-02395-9. 2 Nathan et al. “Long-term Course and Prognosis of Idiopathic Pulmonary Fibrosis in the New Millennium”. Chest Journal Volume 140, ISSUE 1, P221-229, July 2011. Forward-Looking Statements This press release may contain forward-looking statements of Aileron Therapeutics, Inc. (“Aileron”, the “Company”, “we”, “our” or “us”) within the meaning of the Private Securities Litigation Reform Act of 1995, including statements with respect to: the timing and expectation of the results of the Phase 1b study of LTI-03; future expectations, plans and prospects for the Company, the sufficiency of the Company’s cash resources; certain milestones of the Company; the projected cash runway of the Company; the status and plans for clinical trials, including the timing of data; future product development; and the potential commercial opportunity of LTI-03 and LTI-01. We use words such as "anticipate," "believe," "estimate," "expect," "hope," "intend," "may," "plan," "predict," "project," "target," "potential," "would," "can," "could," "should," "continue," and other words and terms of similar meaning to help identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including risks and uncertainties related to, the ability to maintain the listing of the common stock of the Company on The Nasdaq Stock Market, changes in applicable laws or regulations, the possibility that the Company may be adversely affected by other economic, business, and/or competitive factors, including risks inherent in pharmaceutical research and development, such as: adverse results in the Company’s drug discovery, preclinical and clinical development activities, the risk that the results of preclinical studies and early clinical trials may not be replicated in later clinical trials or that partial results of a trial such as the Cohort 1 results from the Company’s ongoing Phase 1b trial will be indicative of the full results of the trial, the Company’s ability to enroll patients in its clinical trials, and the risk that any of its clinical trials may not commence, continue or be completed on time, or at all; decisions made by the U.S. FDA and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies with respect to our development candidates; our ability to obtain, maintain and enforce intellectual property rights for our platform and development candidates; competition; uncertainties as to the sufficiency of the Company’s cash resources to fund its planned activities for the periods anticipated and the Company’s ability to manage unplanned cash requirements; and general economic and market conditions; as well as the risks and uncertainties discussed in the "Risk Factors" section of the Company’s Annual Report on Form 10-K for the year ended December 31, 2023, which is on the United States Securities and Exchange Commission (the “SEC”), and in subsequent filings that the Company files with the SEC. These forward-looking statements should not be relied upon as representing the Company’s view as of any date subsequent to the date of this press release, and we expressly disclaim any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. Investor Relations & Media Contact: Argot Partners aileron@argotpartners.com 212-600-1902

WASHINGTON, Oct. 25, 2023 /PRNewswire/ -- A glimpse into the future of American innovation and emerging technological trends from the nation's brightest young innovators — from a cerebral aneurysm test to biosensors that rapidly identify marine pathogens and harmful algal blooms — were recognized and honored this week at the 2023 Collegiate Inventors Competition®, an annual competition for college and university students and their advisers. Finalist teams (five Undergraduate and five Graduate), consisting of 22 students from eight colleges and universities across the United States, presented their inventions to an esteemed panel of final-round judges composed of the most influential inventors and innovation experts in the nation — National Inventors Hall of Fame® Inductees and United States Patent and Trademark Office (USPTO) officials. "The Collegiate Inventors Competition showcases the next generation of game changers — young inventors who demonstrate an innovative mindset that empowers them to solve the world's greatest challenges," said National Inventors Hall of Fame CEO Michael Oister. "These student teams earned the opportunity this week to meet and learn directly from our nation's greatest innovators — the Inductees of the National Inventors Hall of Fame." Established in 1990, the Collegiate Inventors Competition is a program of the National Inventors Hall of Fame and is sponsored by the USPTO, Arrow Electronics (sponsor of the Arrow Electronics People's Choice Award), and Honda. In addition to cash awards, the winning teams also receive a USPTO Patent Acceleration Certificate. FIRST-PLACE WINNERS ($10,000 PRIZE) UNDERGRADUATE: FADpad, Georgia Institute of Technology Team Members: Netra Gandhi, Rhea Prem, Ethan Damiani and Girish Hari; Adviser: Wendy Cocke Accessible, at-home diagnostics: One of the most common diagnostic tools in women's health, the Papanicolaou test, or Pap smear, is often uncomfortable and regarded as an invasion of privacy, and it is even stigmatized in some cultures. FADpad is an at-home menstrual blood screening tool that allows users to collect their personal health information safely, comfortably and privately. Targeted to users with limited access to the healthcare system, it could help address health disparities and prevent early deaths from cervical cancer among people who menstruate. GRADUATE: Cerebral Aneurysm Test (CAT-7) , University of Pittsburgh School of Medicine Team Member: Adi Mittal; Advisers: Robert M. Friedlander, Kamil Nowicki Enabling earlier aneurysm diagnoses: Affecting an estimated 6.7 million people in the U.S., a cerebral aneurysm (CA) can cause neurological problems and can rupture, leading to life-altering or fatal brain bleeds. Diagnosis can be a long process, current tools are invasive, expensive and potentially toxic, and ruptures often occur before diagnosis or treatment. Cerebral Aneurysm Test (CAT-7) is the first simple, whole blood-based diagnostic test to detect the formation of a CA. It is noninvasive, less expensive, more accurate, safer and able to be used earlier in the care process. RUNNER-UP WINNERS ($5,000 PRIZE) UNDERGRADUATE: Bronchosleeve, Johns Hopkins University Team Members: Sneha Batheja, Ria Jha, Charlie Almoney and Arijit Nukala; Adviser: Brijen Joshi Supporting safety in surgery: One-lung ventilation (OLV), a procedure that provides surgeons with access to organs obstructed by an inflated lung, is required in 98% of pulmonary and cardiothoracic surgeries. However, current OLV devices have a 40% failure rate and a high probability of causing postoperative complications. The Bronchosleeve is a flexible yet sturdy device presenting many advantages over existing OLV devices. It is easy to insert, won't dislodge during surgery and aids visualization with a bronchoscope. In addition to addressing disparities and reducing patient injuries, it could decrease surgical time by 40% and save hospitals over $45,000 per procedure. GRADUATE: Entropic Biosciences Inc., University of California, Los Angeles Team Member: Amir Nasajpour; Adviser: Paul S. Weiss Assembling cells into functional tissue: Establishing tools for recreating functional human tissues and organs has been a grand challenge in biomedical engineering and healthcare. Entropic Biosciences Inc. has developed a bio-inspired rapid sample preparation kit enabling high-throughput culturing of multiple cell types and rapid self-assembly of these cells into 3D self-standing tissue. This technology can be employed to develop an array of tissue types from numerous cell sources. It enables the development of functional tissue and cancer models at faster rates than current technologies, accelerating life science research and drug screening in addition to working toward individualized treatments for cancer patients. ARROW ELECTRONICS PEOPLE'S CHOICE AWARD WINNER ($2,000 PRIZE) NucleoTide, Duke University Team Member: Daniel Collins; Adviser: Peter Nguyen Efficiently monitoring ocean health: Over the past several decades, a combination of natural and human-caused factors has led to an increase in the frequency, duration, size and impact of harmful algal blooms (HABs), with a global economic impact estimated at more than $8 billion annually. NucleoTide is a molecular diagnostic platform that uses CRISPR-based biosensors to rapidly identify marine pathogens and HABs. With a low-cost, hand-held device that filters and processes water samples, it enables lab-free, on-site ocean health monitoring and provides results in less than an hour, offering both economic and environmental benefits. About the Collegiate Inventors Competition The Collegiate Inventors Competition encourages and drives innovation and entrepreneurship at the collegiate level. A program of the National Inventors Hall of Fame, this competition recognizes and rewards the research, innovations and discoveries by college students and their advisers for projects leading to inventions that have the potential of receiving patent protection. Introduced in 1990, the competition has featured more than 500 innovators who have created cutting-edge, world-changing inventions, and awarded more than $1 million of support to winning student teams for their innovative work and scientific achievement through the help of its sponsors. For more information, visit invent.org/collegiate-inventors. CONTACT: Ken Torisky National Inventors Hall of Fame [email protected] 234-901-6085 SOURCE Collegiate Inventors Competition

As climate change warms the Earth, higher-latitude regions will be at greater risk for toxins produced by algal blooms, according to new research. The findings identify water temperatures of 20 to 25 degrees Celsius (68 to 77 degrees Fahrenheit) as being at the greatest risk for developing dangerous levels of a common algae-produced toxin called microcystin. As climate change warms the Earth, higher-latitude regions will be at greater risk for toxins produced by algal blooms, according to new research led by Carnegie's Anna Michalak, Julian Merder, and Gang Zhao. Their findings, published in Nature Water, identify water temperatures of 20 to 25 degrees Celsius (68 to 77 degrees Fahrenheit) as being at the greatest risk for developing dangerous levels of a common algae-produced toxin called microcystin. Harmful algal blooms result when bodies of water get overloaded with nitrogen and phosphorus runoff from agriculture and other human activities. These excess nutrients can allow blue-green algae populations to grow at an out-of-control rate. Some blue-green algal species produce a toxin called microcystin, which can pose a serious health hazard to people and the environment, as well as pose economic risks for fishing and tourism. Microcystin affects liver function and can cause death in wild and domestic animals, including humans in rare instances. It is also classified as a potential carcinogen in cases of chronic exposure. "In 2014 an algal bloom in Lake Erie led to high levels of microcystin in water intakes, and residents in Ohio and Ontario were instructed not to drink tap water due to risk of exposure," Merder cautioned. Merder, Michalak, and their colleagues -- Carnegie's Gang Zhao, University of Kansas's Ted Harris, and Dimitrios Stasinopoulos and Robert Rigby of the University of Greenwich -- analyzed samples taken from 2,804 U.S. lakes between 2007 and 2017. They assessed how water temperature affects the occurrence and concentration of microcystin as part of an effort to better understand the risks to water quality posed by climate change. Michalak's lab has taken a leading role in understanding the intersection of climate change and water quality impairments for more than a decade. Previous work has shown that lakes worldwide are already experiencing more severe algal blooms and that nutrient pollution is being exacerbated by changes in rainfall patterns. "Lakes are sentinels of climate change," Michalak said. "They hold the vast majority, 87 percent, of the liquid freshwater on the Earth's surface, and the warming and precipitation shifts associated with climate change pose some of the greatest threats to water quality around the world and to the health of aquatic ecosystems." The surface temperatures of lakes have already been warming at 0.34 degrees Celsius (0.61 degrees Fahrenheit) per decade and Merder and Michalak set out to determine what this, as well as future warming, would mean in terms of risk for elevated toxin concentrations. "The abundance of blue-green algae is predicted to increase due to climate change as they outcompete other species," Merder explained. "But previous field studies came to various conclusions about what this means for microcystin concentrations." To inform land and water management strategies, it was important to quantitatively tie toxin levels to water temperature, which Merder and Michalak were able to accomplish through their extensive analysis of lake water samples, revealing that water temperatures in the 20 to 25 degrees Celsius (68 to 77 degrees Fahrenheit) range were most dangerous in terms of elevated microcystin concentrations. They also found that the impact of temperature is amplified when nutrient concentrations are high. By incorporating information from climate models, they were able to demonstrate that areas most susceptible to high toxin concentrations will continue to move northward. In some areas, the relative risk of exceeding water quality guidelines will increase by up to 50 percent in the coming decades. Additionally, they showed that toxin hazards will decrease in a small number of regions further south, as water temperatures begin to exceed those associated with the highest risk. "These findings should help demonstrate the serious risk to safe water for drinking, fishing, recreation, and other societal needs in many parts of the United States and the urgency for developing management strategies to prepare," Michalak concluded. "When we think about water sustainability in the context of global change, we need to focus on the quality of the water as much as we focus on the amount of water."