New clinical trial design in precision medicine: discovery, development and direction

Aileron Therapeutics Completes Enrollment In Cohort 2 Of The Ongoing Phase 1b Clinical Trial Evaluating LTI-03 In Idiopathic Pulmonary Fibrosis (IPF)

Cohort 2 will evaluate high-dose LTI-03 (5 mg BID)

Previously announced Cohort 1 data demonstrated positive trends in seven of the eight biomarkers evaluated, suggesting a potential therapeutic effect

AUSTIN, Texas, Sept. 23, 2024 /PRNewswire/ -- 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 the completion of enrollment in Cohort 2 of the ongoing Phase 1b clinical trial of LTI-03 in IPF patients.

Aileron logo (PRNewsfoto/AILERON THERAPEUTICS)

The last patient was enrolled in mid-September, with a total of 24 patients enrolled in the trial. Eligible patients are randomly assigned (3:1) to receive either inhaled LTI-03 or placebo. The primary objective of the trial is to evaluate the safety and tolerability of LTI-03 in patients with IPF after treatment for 14 consecutive days, with measurement of multiple protein biomarkers as exploratory endpoints.

"We are pleased to have completed enrollment in the high-dose cohort of our Phase 1b clinical trial and grateful to all participating patients and investigators," said Brian Windsor, Ph.D., President and Chief Executive Officer of Aileron. "Following the positive trend observed in the low-dose cohort, we are excited to assess the safety, tolerability and biomarkers of 5 mg twice daily of inhaled LTI-03 and expect to report topline data in the near term."

In May 2024, the Company announced positive data from Cohort 1 evaluating low-dose LTI-03 (2.5 mg BID). Following inhaled administration of low-dose LTI-03 in 12 patients, a positive trend was observed in seven out of eight biomarkers with evidence of reduced expression among multiple profibrotic proteins produced by basal-like cells and fibroblasts that contribute to the progression of IPF, including data from three biomarkers that was statistically significant, reinforcing the potential of LTI-03 to improve lung function and reverse the course of IPF.

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 trial 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 inhaled LTI-03 or placebo. The primary objective of the trial is to investigate the safety and tolerability of LTI-03 in patients with IPF after treatment for 14 consecutive days, with measurement of multiple protein biomarkers 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 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. 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 topline results of Cohort 2 of the Phase 1b clinical trial of LTI-03; future expectations, plans and prospects for the Company, the sufficiency of the Company's cash resources; 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, 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 clinical 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. Food and Drug Administration 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 and Quarterly Report on Form 10-Q for the quarter ended June 30, 2024, which are on file with the United States Securities and Exchange Commission (the "SEC"), and in subsequent filings that the Company makes 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 Partnersaileron@argotpartners.Com212-600-1902

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SOURCE Aileron Therapeutics, Inc.

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Mosliciguat's Early Efficacy Results Support Launch Of Phase 2 Study

Treatment with mosliciguat, an inhaled medication given once-daily for pulmonary hypertension (PH), can safely reduce the resistance against blood flow in blood vessels of the lungs, according to a Phase 1 clinical trial.

This reduction in pulmonary vascular resistance (PVR) is one of the highest seen in PH trials to date, stated the treatment's developer, Pulmovant.

Results were presented recently at the European Respiratory Society Congress in Vienna, Austria.

"We believe mosliciguat can transform the lives of patients living with pulmonary hypertension, and I am excited to announce this potential first-in-class and best-in-category therapy," Matt Gline, CEO at Roivant Sciences, the parent company of Pulmovant, said in a press release.

PH is characterized by the narrowing of blood vessels that supply blood to the lungs. Mosliciguat is designed to widen blood vessels, even when there is low oxygen in the lungs and oxidative stress (which occurs when oxidant molecules outweigh the body's antioxidant defenses), and it may have anti-inflammatory and antiscarring properties, according to Pulmovant.

Mosliciguat targets sGC enzyme that drives blood vessel widening

Mosliciguat targets soluble guanylate cyclase (sGC), an enzyme that ultimately drives blood vessel widening. Specifically, mosliciguat works in the nitric oxide/cGMP pathway, resulting in the production of the cGMP molecule.

To be effective, other sGC activators need heme, which is a ring-shaped compound that can bind nitric oxide. In contrast, mosliciguat does not require heme or nitric oxide to work. According to Pulmovant, this enables the treatment candidate to remain effective even in the highly oxidative environments typical of PH, as these environments can make sGC activators lose efficacy because heme is oxidized or removed, and nitric oxide levels are depleted.

The proof-of-concept Phase 1b clinical trial ATMOS (NCT03754660) assessed mosliciguat's safety, tolerability, and efficacy in people with pulmonary artery hypertension or chronic thromboembolic pulmonary hypertension, a rare form of PH associated with blood clot formation.

A total of 38 participants, ages 18 to 80, received a daily dose of mosliciguat using a dry powder inhaler (DPI). In 20 patients, mosliciguat, administered at 1, 2, and 4 mg daily, achieved a mean reduction in PVR of 25.9%, 38.1%, and 36.3%, respectively, from the start of the study. These results exceeded the primary threshold of a minimum 20% reduction. A similar effect was seen in participants who did not respond to inhaled nitric oxide.

"We are impressed with the data generated so far, particularly the PVR results," Gline said.

Phase 1 data support once-daily dosing of mosliciguat

Overall, along with a favorable safety profile in a total 170 healthy participants and PH patients during Phase 1, pharmacology data has supported once-daily dosing. This is a notable difference from current approved PH therapies that require multiple inhalations per day, Pulmovant stated.

The DPI formulation is more convenient for patients than nebulizers, which convert medications to an inhalable mist, according to the company. Also, direct lung delivery lowers the risk of side effects such as drops in oxygen levels, seen with blood vessel wideners given via other routes. This may make the treatment effective in different PH types, Pulmovant stated.

"Mosliciguat has the incredibly rare advantage of potential differentiation across three separate key areas — efficacy, safety, and convenience in administration," Gline said.

Advancing with the mosliciguat clinical program, a Phase 2 trial called PHocus will enroll approximately 120 patients with PH associated with interstitial lung disease (PH-ILD), a condition that causes the lungs to become scarred.

"We have elected to initiate our global Phase 2 PHocus study in PH-ILD because of the lack of treatment options for patients coupled with the impressive Phase 1b results and strong biologic rationale," said Drew Fromkin, Pulmovant's CEO. "We are committed to making a significant difference for these patients and have assembled a stellar team, alongside our world-class investigators and advisors, to advance and optimize mosliciguat's development."

Convergent Therapeutics Announces First Patient Treated In Phase II Clinical Trial With Lead Therapeutic Candidate And Corporate Updates

PR Newswire

CAMBRIDGE, Mass., Sept. 24, 2024

CAMBRIDGE, Mass., Sept. 24, 2024 /PRNewswire/ -- Convergent Therapeutics Inc., a clinical stage biotechnology company focused on developing next generation radiopharmaceutical therapies for the treatment of prostate cancer and other cancers, today announced that the first patient has been dosed with CONV01-a in the Phase II CONVERGE-01 trial evaluating CONV01-a, Ac-225 rosopatamab tetraxetan, for the treatment of patients with prostate-specific membrane antigen (PSMA) PET-positive metastatic castration resistant prostate cancer (mCRPC).

The CONVERGE-01 trial is a Phase II, randomized, open-label, multicenter three-part study designed to assess the safety and efficacy of CONV01-a in patients with mCRPC. In Part 1, the first 5 participants will receive In-111-rosopatamab tetraxetan to characterize the biodistribution of the radioantibody to target organs and prostate cancer lesions. Participants will then be enrolled in either Part 2 (dose optimization) or Part 3 (dose escalation) depending on their prior treatment history. Part 2 will enroll Lu-177-PSMA-radioligand therapy-naïve participants and Part 3 will enroll participants who received prior Lu-177-PSMA-radioligand therapy. All patients will receive Ac-225 rosopatamab tetraxetan in a single fractionated two-week cycle.  Further details of the trial can be found at www.Clinicaltrials.Gov under NCT identifier: NCT06549465.

Chief Medical Officer Appointment

Convergent announced that Richard Messmann, MD, MHS, MSc, has joined the company as Chief Medical Officer. Dr. Messmann is a medical oncologist and biochemist with over 25 years of experience in oncology drug development, including responsibility for the global clinical development and successful regulatory submission of Pluvicto® and Locametz® for the treatment of men with PSMA-expressing, mCRPC. Dr. Messmann has held leadership positions at Endocyte, Advanced Accelerator Applications (a subsidiary of Novartis), Fusion Pharmaceuticals, Amgen, Eli Lilly & Co., and others.

Immediately prior to joining Convergent Therapeutics, Dr. Messmann was the Senior Vice President and clinical lead for Fusion's development of the actinium radiotherapeutic FPI-2265. While at Amgen, he was the executive medical director and global program lead for the development of xaluritamig (AMG 509) in prostate cancer.

"We are excited to welcome Dr. Messmann to the Convergent team as we expand our clinical program for CONV01-a," said Convergent's Co-founder and CEO, Philip Kantoff, MD. "His deep knowledge and experience in oncology drug development, specifically leading the late-stage development of radiopharmaceuticals, is an important addition to our team as we look forward to progressing this asset forward." 

Series A Extension Funding

Convergent announced a $40 million Series A extension by Novo Holdings, a holding and investment company wholly owned by the Novo Nordisk Foundation. This additional funding increases the total Series A raise to $130 million to support the development of Convergent's radiopharmaceutical pipeline, including CONV01-a. Jim Trenkle, PhD, Partner in the Venture Investments group at Novo Holdings, joins the Convergent Board of Directors.  

About CONV01-aCONV01-a, Convergent's alpha emitting radioantibody, combines the precision and pharmacokinetics of antibodies with the tumor-killing potential of alpha emitting radionuclides. Specifically, CONV01-a uses a humanized monoclonal antibody targeting prostate-specific membrane antigen (PSMA) which is highly overexpressed in prostate cancer cells. Since PSMA is a validated target, several therapeutics are directed at this antigen and CONV01-a is differentiated by its use of both an antibody and alpha emitter. CONV01-a is linked to a powerful radionuclide called 225Ac, which releases alpha particles which kill cancer cells through DNA double strand breaks. Unlike other radioactive sources, alpha particles deliver high-energy radiation over very short distances, thereby minimizing radiation exposure to healthy neighboring cells and tissues. Pairing highly selective antibodies with such a powerful yet precise payload offers the ideal combination to treat many types of cancers.

About Convergent Therapeutics, Inc.Convergent Therapeutics Inc. Is a clinical-stage biotechnology company focused on developing tumor-selective alpha radioantibodies to target cancer. The company was founded by world-renowned experts in clinical care and research, drug development and cancer biology and its proprietary platform is licensed from Cornell University. In harnessing the selectivity of antibodies and tumor-destructive potential of alpha radioisotopes, Convergent's radioantibodies precisely target cancer cells with potent, localized radiation. For more information, please visit www.Convergentrx.Com and follow us on Twitter and LinkedIn.

Media Relations:Bryan BlatsteinSpectrum [email protected] 

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SOURCE Convergent Therapeutics

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