St James's University Hospital

German drugmaker Boehringer Ingelheim didn’t share any data behind the top-line result, instead promising that the efficacy and safety findings would be unveiled in the second quarter.\n Boehringer Ingelheim has cemented the potential of its idiopathic pulmonary fibrosis (IPF) drug with a second phase 3 win in a related lung disease leading the drugmaker to expand the indications it will seek FDA approval for.The FIBRONEER-ILD trial saw 1,178 patients with progressive pulmonary fibrosis (PPF) receive either a 9 mg or 18 mg dose of the PDE4B inhibitor nerandomilast or placebo twice a day for 52 weeks. The study hit its primary endpoint of demonstrating an absolute change from baseline in forced vital capacity—a measure of the volume of air that a patient can breathe out—Boehringer said in a Feb. 10 release.The German drugmaker didn’t share any data behind the top-line result, instead promising that the efficacy and safety findings would be unveiled in the second quarter.“Initial data readouts of the FIBRONEER trials support a generally consistent safety and tolerability profile when compared to the phase 2 IPF study, with overall adverse events comparable to those seen in the placebo group,” the company said.Armed with the latest results, Boehringer said it will request that FDA and global regulators approve nerandomilast as a treatment for PPF, a type of interstitial lung disease. The company has already said it will seek approval for nerandomilast in IPF after proclaiming a win in a phase 3 trial for that lung disease in September 2024. Again, the company opted to hold back any concrete data from that trial for later in this year.When it comes to managing IPF, physicians already have Boehringer’s Ofev and Roche’s Esbriet. However, those drugs only slow the progression of fibrosis, while attempts to produce molecules that further slow, or ideally stop, progression have failed to prove their worth.By targeting phosphodiesterase 4B (PDE4B), nerandomilast is meant to have a mechanistic advantage over the incumbent products. Targeting PDE4 drives anti-inflammatory and antifibrotic effects, but attempts to develop oral inhibitors of the enzyme in respiratory diseases have been hindered by class-related systemic adverse events such as diarrhea and headaches.“The positive FIBRONEER-ILD topline result shows the potential of nerandomilast in progressive pulmonary fibrosis,” Shashank Deshpande, Head of Human Pharma at Boehringer, said in the release. “The hope is that the safety and tolerability profile we are initially seeing could potentially help to reduce treatment challenges.”

Meaningful tumor shrinkage observed in five out of 10 patients with partial and minor responses and 90% disease control rate in patients with salivary gland cancers Phase 1b expansion cohorts screening patients in triple negative breast cancer, soft tissue sarcoma and salivary gland cancer LONDON, UK and PHILADELPHIA, PA, USA I January 16, 2025 I Avacta Therapeutics (AIM: AVCT), a life sciences company developing next generation peptide drug conjugates (PDC) targeting powerful anti-tumor payloads directly to the tumor, today announced compelling new data in patients with salivary gland cancer (SGC) from the ongoing Phase 1a trial of AVA6000 in patients with FAP-positive solid tumors. The data demonstrates robust and meaningful tumor shrinkage in patients with salivary gland cancers, a disease with no standard therapy defined in the metastatic setting. AVA6000 is the first peptide drug conjugate in Avacta’s pipeline and consists of doxorubicin conjugated with Avacta’s proprietary pre|CISION ® peptide, that is specifically cleaved by fibroblast activation protein-alpha (FAP) in the tumor microenvironment. The key findings include: Based on this favorable efficacy and safety data observed in the Phase 1a trial, Avacta has initiated three Phase 1b expansion cohorts in triple negative breast cancer, soft tissue sarcoma and salivary gland cancer in the first and second line setting. Patients are screening and the first patients to be treated in these expansions are expected imminently in the US. Christina Coughlin MD, PhD, CEO of Avacta , commented, “These data highlight the transformative potential of our pre|CISION ® peptide drug conjugates in expanding the efficacy of highly potent therapeutics and support our growing optimism in this program. “Salivary gland cancer is a devastating disease with no established standard of care treatment options. AVA6000 demonstrated a clinically meaningful tumor shrinkage in SGC patients, highlighting its potential as an important new treatment option for patients with SGC and other solid tumors. “We look forward to continuing to work with our investigators and the broader community to explore its potential in SGC and other cancers. We are thrilled to begin enrollment in the expansion cohorts, and this part of the trial will also be conducted in less heavily pretreated patients which will allow us to better understand the potential of AVA6000 in these disease settings with high unmet need.” These results demonstrate preliminary evidence of durable antitumor activity in patients with SGC, supported by ongoing RECIST 1 responses (both partial and minor responses) in a disease setting with no standard of care. SGC accounts for 6-8% of head and neck cancers in the US, with approximately 2,500 cases diagnosed in the US each year 2 . There is no standard of care for SGC once patients have developed distant metastasis, with a five year survival rate of approximately 43%. Clinical data observations: Out of 10 patients with SGC treated at the dose of 250 mg/m 2 and above, 5 patients experienced clinically meaningful disease shrinkage, including a confirmed partial response (PR, 45% tumor shrinkage) and four minor responses (MR, 10-19.5% tumor shrinkage) using RECIST criteria. 1 These data include the following cases: Although these data are reported early in the treatment course of most patients, it is notable that six patients (of the 10 patients with SGC), including all five responders, remain on treatment and a further two patients remain in progression-free follow-up after having received the maximum number of cycles of AVA6000. Only one patient has reported disease progression as best response resulting in the disease control rate of 90% in this group of patients with salivary gland cancers. Treatment with AVA6000 continues to be well-tolerated in both dosing arms, once every two weeks (Q2W) and once every three weeks (Q3W), with reduced hematologic and cardiac toxicities compared to conventional dose doxorubicin at 75 mg/m 2 dosed every 3 weeks. A maximum tolerated dose has not been identified in either arm of the trial. 1 Reduction in the sum of longest diameters (SLD) is used to measure response per RECIST 1.1 with partial responses having at least a 30% reduction and minor responses of between >10% and <30% reduction. 2 American Cancer Society: Key Statistics in Salivary Gland Cancers, www.cancer.org/cancer/types/salivary-gland-cancer.html. About Avacta – avacta.com Avacta Therapeutics is a clinical-stage life sciences company expanding the reach of highly potent cancer therapies with the pre|CISION ® platform. pre|CISION ® is a proprietary warhead delivery systembased on a tumor-specific protease (fibroblast activation protein or FAP) that is designed to concentrate highly potent warheads in the tumor microenvironment while sparing normal tissues. Our innovative pipeline consists of pre|CISION ® peptide drug conjugates (PDC) or Affimer ® drug conjugates (AffDC) that leverage the tumor-specific release mechanism, providing unique benefits over traditional antibody drug conjugates. About the pre|CISION ® Platform The pre|CISION ® platform comprises an anticancer payload conjugated to a proprietary peptide that is a highly specific substrate for fibroblast activation protein (FAP) which is upregulated in most solid tumors compared with healthy tissues. The pre|CISION ® platform harnesses this tumor specific protease to cleave pre|CISION ® peptide drug conjugates and pre|CISION ® antibody/Affimer ® drug conjugates in the tumor microenvironment, thus releasing active payload in the tumor and reducing systemic exposure and toxicity, allowing dosing to be optimized to deliver the best outcomes for patients. About AVA6000: FAP-enabled doxorubicin The lead pre|CISION ® program AVA6000, a peptide drug conjugate form of doxorubicin, is in Phase 1 studies. It has shown an improvement in safety and tolerability in clinical trials to date compared with standard doxorubicin and preliminary signs of clinical activity in multiple patients. SOURCE: Avacta Therapeutics