isunakinra (EBI-005) / Buzzard Pharma - LARVOL DELTA

Targeting KRAS-mutant Lung Adenocarcinoma Tumors Through IL-1ß Inhibition (ATS 2025) - "CONCLUSIONS Overall, our data suggest that Isunakinra effectively influences the KRAS tumorgenicity via CCL2 signaling loop, reducing tumor growth by modulating the immune microenvironment. These results support its further investigation as a modulator of immune signaling and immune cell recruitment, and as a therapeutic approach for KRAS-mutated LUAD."

Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CCL2 • CCR2 • CD68 • KRAS

Isunakinra Alone and in Combination with Pembrolizumab in Patients with Colorectal Cancer (MSS) (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: Buzzard Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Tumor mutational burden • Colorectal Cancer • Oncology • Solid Tumor

Isunakinra Alone and in Combination with Pembrolizumab in Patients with Colorectal Cancer (MSS) (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: Buzzard Pharmaceuticals

New P2 trial • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Isunakinra Alone and in Combination With a PD-1/PD-L1 Inhibitor in Patients With Solid Tumors (clinicaltrials.gov) - P1/2 | N=15 | Completed | Sponsor: Buzzard Pharmaceuticals | Recruiting ➔ Completed | N=25 ➔ 15 | Trial completion date: Dec 2024 ➔ Jul 2024 | Trial primary completion date: Jul 2024 ➔ Dec 2023

Combination therapy • Enrollment change • Metastases • Trial completion • Trial completion date • Trial primary completion date • Oncology • Prostate Cancer • Solid Tumor • CRP • IL6

Isunakinra as Monotherapy and Combined with Nivolumab for Treatment Resistant Advanced Solid Tumours: Exploratory Effect Data, Tolerability, and Pharmacokinetics from a Dose Escalation Trial (ESMO-IO 2023) - P1/2 | "Isunakinra, an anakinra-like IL-1R1 antagonist, blocks IL-1α/IL-1β 10-20x more potently in various assays. No serious events related to the combination therapy. Encouraging exploratory data with signs of tumour control in heavily pre-treated subjects along with currently obtained pharmacokinetic and safety profiles justifies exploring further CPI combinations in planned phase 2 studies."

Metastases • Monotherapy • PK/PD data • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CTCs • IL1B • KRAS

A phase I study of isunakinra, an IL-1 alfa/beta inhibitor, in combination with nivolumab for patients with solid tumors refractory to standard therapies. (ASCO 2023) - P1/2 | "Isunakinra is safe and well-tolerated in combination with standard dose nivolumab. Ongoing expansion cohorts and future studies will explore the safety and efficacy of isunakinra in specific tumors and with other immunotherapy combinations. Clinical trial information: NCT04121442."

Clinical • Combination therapy • P1 data • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CXCL8 • IL1B • IL1R1 • IL6 • KRAS • TMB

Isunakinra Alone and in Combination With a PD-1/PD-L1 Inhibitor in Patients With Solid Tumors (clinicaltrials.gov) - P1/2 | N=25 | Recruiting | Sponsor: Buzzard Pharmaceuticals | Trial completion date: Jul 2023 ➔ Dec 2024 | Trial primary completion date: Jan 2023 ➔ Jul 2024

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Oncology • Prostate Cancer • Solid Tumor • CRP • IL6

[VIRTUAL] LSC - 2021 - Preclinical evaluation of IL-1ß inhibition against KRAS-mutant lung adenocarcinoma (ERS 2021) - "To test this, we used a novel, specific inhibitor of IL-1ß signaling called isunakinra and cancer cell lines stably expressing a NF-?B reporter bioluminescent plasmid, in both in vitro and in vivo assays...Similar results were also obtained using the flank tumor model, in which the drug was effective in reducing primary tumor volume and occurrence of pulmonary metastases. Collectively, our results show that IL-1ß inhibition may constitute a novel therapeutic strategy to target KRAS-mutant tumors."

Preclinical • Lung Adenocarcinoma • Lung Cancer • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Respiratory Diseases • Solid Tumor • KRAS

Isunakinra Alone and in Combination With a PD-1/PD-L1 Inhibitor in Patients With Solid Tumors (clinicaltrials.gov) - P1/2; N=25; Recruiting; Sponsor: Buzzard Pharmaceuticals; Trial completion date: Jul 2022 ➔ Jul 2023; Trial primary completion date: Jan 2021 ➔ Jan 2023

Clinical • Combination therapy • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • CRP • IL6

Experimental Pharmacotherapy for Dry Eye Disease: A Review. (PubMed, J Exp Pharmacol) - "Moreover, the most advanced experimental strategies in the pipeline for DED, tivanisiran, IL-1R antagonist EBI-005 and SkQ1, are being tested in Phase III clinical trials, still ongoing. Nevertheless, although promising results, further studies are still needed to confirm efficacy and safety of the new emerging therapies for DED."

Journal • Review • Dry Eye Disease • Immunology • Inflammation • Ocular Infections • Ocular Inflammation • Ophthalmology • Pain

Isunakinra Alone and in Combination With a PD-1/PD-L1 Inhibitor in Patients With Solid Tumors (clinicaltrials.gov) - P1/2; N=25; Recruiting; Sponsor: Buzzard Pharmaceuticals; Not yet recruiting ➔ Recruiting; Initiation date: Jan 2020 ➔ Sep 2020

Clinical • Combination therapy • Enrollment open • Trial initiation date • Alzheimer's Disease • Oncology • Prostate Cancer • Solid Tumor • IL6

Eleven Biotherapeutics reports clinical and regulatory updates for EBI-005 (Eleven Biotherapeutics Press Release) - "Eleven...announced that it received a no-objection letter from Health Canada and that patient dosing is underway in the Company’s Phase 2 clinical trial of EBI-005 for the treatment of allergic conjunctivitis (AC)....This Phase 2 trial is expected to include approximately 150 subjects in Canada."; P3, N=730; Sponsor: Eleven Biotherapeutics; NCT01998802; Anticipated top line P2 data in H2 2014 and P3 top-line data in early 2015; Anticipated second pivotal Phase 3 trial in dry eye disease (DED) in US; "The Company will continue to evaluate the scientific advice received from the EMA and plans to further discuss with the EMA a registration plan for EBI-005 in DED for the European Union."

Anticipated EU regulatory • Anticipated new P3 trial • Anticipated P3 data • Anticipated target enrollment • Canadian regulatory • European regulatory • P2 data • Immunology

Eleven Biotherapeutics to present at the targeting ocular disorders conference (Eleven Biotherapeutics Press Release) - "Eleven Biotherapeutics...announced today, that Eric Furfine...is scheduled to present at the Targeting Ocular Disorders Conference being held September 26-27, 2013...Dr. Furfine will discuss new approaches to cytokine signaling blockade for the treatment of ocular disease, highlighting examples from Eleven Biotherapeutic’s proprietary product pipeline, including interleukin-1 blockade with EBI-005 for the treatment of dry eye disease."

Anticipated pipeline update • Immunology

Multicenter Study of a Novel Topical Interleukin-1 Receptor Inhibitor, Isunakinra, in Subjects With Moderate to Severe Dry Eye Disease. (PubMed, Eye Contact Lens) - "Isunakinra was safe, well tolerated and showed clinically meaningful improvements in signs and symptoms of DED. These results encouraged the design of an adequately powered study to characterize the safety and efficacy of isunakinra in ocular surface diseases."

Clinical • Journal • Biosimilar • CNS Disorders • Dry Eye Disease • Ophthalmology • Pain

Eleven Biotherapeutics: Q3 FY 2015 Results (Eleven Biotherapeutics) - Anticipated data from truncated safety P3 study (NCT02405039) in dry eye disease in Q1 2016

Anticipated P3 data • Immunology

Eleven Biotherapeutics: ARVO 2016 (Eleven Biotherapeutics) - "The results of this study corroborate the safety and tolerability of isunakinra (and vehicle control), which has been observed in previous studies in patients with DED and allergic conjunctivitis (AC)"; "Although not powered for efficacy, the general improvement from baseline in OSDI and CFS scores observed in both treatment groups in this study has been observed in previous studies of isunakinra (and vehicle control) in patients with DED and AC"; "In both the isunakinra and vehicle control treated groups, at least 62% of subjects had an improvement from baseline at 3 and 6 months for both sign and symptoms of DED"; "Subjects treated with isunakinra continued to show an improvement in signs of symptoms of dry eye disease at 6 months compared with 3 months with no plateau of effect seen"

P3 data • Immunology

Eleven Biotherapeutics: Q3 2014 Results (Eleven Biotherapeutics) - Anticipated data from P2 trial for allergic conjunctivitis at the Medical Contact Lens and Ocular Surface Association's annual meeting (Nov 28, 2014); Anticipated top-line data from P3 trial for dry eye disease in Q2 2015

Anticipated P2 data • Anticipated P3 data: top line • Immunology

Eleven Biotherapeutics: Q3 2014 Results (Eleven Biotherapeutics) - Anticipated composition of matter patent expiry in US in 2031; Anticipated method of use patent expiry in US in 2031

Anticipated patent expiry • Immunology

Eleven Biotherapeutics: Clinical Update (Eleven Biotherapeutics) - Anticipated topline data from first P3 trial EBI-005-AC-2 (NCT02492321) for moderate-to-severe allergic conjunctivitis in Q1 2016; Anticipated initiation of second P3 trial for allergic conjunctivitis in H2 2016

Anticipated new P3 trial • Anticipated P3 data: top line • Immunology

Eleven Biotherapeutics: ARVO 2016 (Eleven Biotherapeutics) - "No difference was seen compared to vehicle-control in the co-primary endpoints of mean change from baseline at week 12 for total corneal fluorescein staining score (CFS, sign) or the OSDI pain question (symptom)"; "There was a statistically significant difference from baseline to week 12 within each treatment group for the co-primary endpoints of CFS and the OSDI pain question"; "Isunakinra was safe and well tolerated in this study and had a similar adverse event profile to prior studies in dry eye"; "The majority of patients improved from baseline while on treatment and were able to remain on treatment over the 12 weeks regardless of which treatment arm they participated in"

P3 data • Immunology

Eleven Biotherapeutics: Q4 2014 Results (Eleven Biotherapeutics) - Anticipated BLA filing for moderate to severe dry eye disease by end of 2016

Anticipated BLA • Immunology

Eleven Biotherapeutics: Annual Report 2014 (Eleven Biotherapeutics) - Anticipated composition of matter patent expiry in US, Australia, Brazil, Canada, China, Europe, India, Israel, Japan, Korea, Mexico, New Zealand, Russia, Singapore, South Africa and Taiwan in 2031; Anticipated formulation patent expiry in US in 2034; Anticipated expiry of methods of manufacturing patent in US, Australia, Brazil, Canada, China, Europe, India, Japan, Russia and Singapore in 2032; Anticipated expiry of patents covering use of IL-1 inhibitors in US, Australia, Canada, Europe and Japan to treat certain ocular disease in 2028 and 2030 

Anticipated patent expiry • Immunology

Eleven Biotherapeutics: Oppenheimer & Co. Healthcare Conference (Epizyme) - “Well Tolerated and Biologically Active In EE50 Patient Population“; “Results from phase 1b/2a: EBI-005 (5 & 20 mg/mL) was well tolerated with no SAEs reported, No drug detected in serum levels and no evidence of drug-specific antibodies, Significant reduction in the use of artificial tears for EBI-005 treated subjects in EE population“
 

P1/2 data • Immunology

Eleven Biotherapeutics: Future Leaders in the Biotech Industry Conference (Eleven Biotherapeutics) - "EBI-005-2: SIGN: Total Corneal Flourescein Staining"; "Mean change in Total CFS (EE Population): 33% Change from Baseline"; "Mean change in Total CFS (EE50  Population): 39% Change from Baseline"; "EBI-005-2: SYMPTOM: Painful or Sore Eyes"; "Mean change in score on Painful or Sore eyes OSDI Question (EE Population): 46% Change from Baseline"; "Mean change in score on Painful or Sore eyes OSDI Question (EE50 Population): 61% Change from Baseline"

P1/2 data • Immunology

Eleven Biotherapeutics: BioCentury Newsmakers in the Biotech Industry Conference (Eleven Biotherapeutics) - Anticipated initiation of second P3 trial for allergic conjunctivitis in mid-2016; Anticipated BLA filing for allergic conjunctivitis in H2 2017

Anticipated BLA • Anticipated new P3 trial • Immunology