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 reports phase 3 data on isunakinra (EBI-005) in allergic conjunctivitis (Eleven Biotherapeutics Press Release) - P3, N=250; NCT02492321; Sponsor: Eleven Biotherapeutics; “Isunakinra misses primary endpoint of ocular itching...there were no statistically significant differences between the isunakinra treated group and the vehicle control group on the primary endpoint of ocular itching or on any secondary endpoints. Isunakinra was generally well tolerated, with 94% of the patients completing the trial and there were no serious adverse events reported....Despite this outcome, [the company] plan[s] to continue to assess interleukin-1 (IL-1) genotyping in ocular surface diseases by evaluating data from patient subsets...."

P3 data: top line • Immunology

Eleven Biotherapeutics presents phase 2 clinical data on EBI-005 for the treatment of allergic conjunctivitis at ASCRS 2015 Annual Meeting (Eleven Biotherapeutics Press Release) - "Eleven Biotherapeutics...will present clinical data for EBI-005, its novel, protein therapeutic which is in late-stage clinical development for dry eye disease and allergic conjunctivitis, at the American Society of Cataract and Refractive Surgery (ASCRS) 2015 Annual Meeting in San Diego, CA."; Anticipated new P3 trial in H2 2015.

Anticipated conference • Anticipated new P3 trial • P2 data • Immunology

Multi-center study subjects with dry eye disease (EBI-005) (clinicaltrials.gov) - P3, N=730; Sponsor: Eleven Biotherapeutics; Not yet recruiting -> Recruiting.

Enrollment open • Immunology

Eleven Biotherapeutics: Q1 2014 Results (Eleven Biotherapeutics) - Anticipated top-line data from P2 trial for allergic conjunctivitis in patients who have not responded adequately to antihistamines and mast cell stabilizers in Q4 2014; Anticipated initiation of twelve-month safety pivotal P3 trial for dry eye disease in H2 2014 

Anticipated new P3 trial • Anticipated P2 data • Anticipated trial initiation date • Immunology

Eleven Biotherapeutics: Q1 2015 Results (Eleven Biotherapeutics) - Anticipated presentation of P2 (NCT02082899) data for late phase allergic conjunctivitis at ARVO (May 3-7, 2015); Anticipated presentation of P2 data for moderate to severe dry eye disease at ARVO (May 3-7, 2015)

Anticipated P2 data • Immunology

Eleven Biotherapeutics: Annual Report 2014 (Eleven Biotherapeutics) - Anticipated approval for allergic conjunctivitis in 2017 or after; Anticipated launch for allergic conjunctivitis in 2017 or after  

Anticipated launch • Anticipated regulatory • Immunology

Eleven Biotherapeutics: Oppenheimer & Co. Healthcare Conference (Eleven Biotherapeutics) - Anticipated composition of matter patent expiry in 2031

Anticipated patent expiry • Immunology

Eleven Biotherapeutics: ARVO 2016 (Eleven Biotherapeutics) - "Isunakinra (formerly EBI-005) is an Interleukin-1 receptor inhibitor which demonstrated statistically significant improvement in ocular itching, ocular tearing and total nasal symptoms in a direct conjunctival allergen repeat challenge model in a P2 trial but did not show statistically significant separation from vehicle in this P3 environmental trial"; "Isunakinra was generally safe and well tolerated in this study over the one month study period"; "Most subjects in this study showed an improvement from baseline for both signs and symptoms of allergic conjunctivitis in both the isunakinra treated group and vehicle control group. This improvement was greater than improvement seen during treatment with topical olopatadine alone"; "Post-hoc analysis to assess clinical relevance of high IL-1 producers identified by genotyping demonstrated a group of subjects with greater response to isunakinra therapy relative to vehicle than was seen for the overall study population (ITT)"

P3 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

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: 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