Updated Phase 2 CAPTIVATE Study Results

June 14, 2024

At 5 years, 67 percent of patients were progression-free, with overall survival at 96 percent for all treated patients ¹

Janssen-Cilag International NV, a Johnson & Johnson company, today announced updated findings from the Phase 2 CAPTIVATE study evaluating fixed-duration (FD) IMBRUVICA^® (ibrutinib) in combination with venetoclax (I+V) in previously untreated patients with chronic lymphocytic leukaemia (CLL).¹ At 5.5-years of follow-up, the FD regimen continues to demonstrate a clinically meaningful progression-free survival (PFS), both in the overall population and in those with high-risk genomic features.¹ The data were featured in an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #7009) in Chicago from 31 May – 4 June and as an encore presentation at the European Hematology Association (EHA) Congress (Poster #P675) in Madrid, Spain, from 13-16 June 2024.

“After more than five years, the CAPTIVATE study findings confirm the sustained benefit of the fixed duration combination of ibrutinib and venetoclax as a first-line treatment for patients living with CLL, including in those with higher risk genomic features,” said Paolo Ghia MD, Università Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milan, Italy, study investigator.^‡ “This all-oral, chemotherapy-free, fixed-duration regimen offers eligible patients the advantage of an extended, treatment-free interval while effectively keeping their disease under control.”

Latest findings from the multicentre Phase 2 CAPTIVATE study showed that at a median follow-up of 61.2 months, 67 percent (95 percent confidence interval [CI]: 59-74) of the 159 patients treated with FD I+V, were progression-free and alive at 5-years.¹ Notably, median PFS was not reached even after up to 5.5 years of follow-up, indicating sustained disease control.¹ The 5-year overall survival (OS) rate was 96 percent for all treated patients, while those who had high-risk genomic features (del(17p)/ mutated TP53, or complex karyotype) exhibited an OS rate of 90 percent (95 percent CI: 77-96), compared to 100 percent for those without these features.¹ Moreover, for patients who achieved undetectable minimal residual disease (uMRD) status in the blood and bone marrow, this was associated with improved outcomes.¹ Patients with uMRD in the bone marrow at 3-months post end of treatment (EoT+3 months) had a 5-year PFS rate of 84 percent (95 percent CI: 73-90) compared to 50 percent (95 percent CI: 36-62) for those not achieving uMRD in the bone marrow at EoT+3 months.¹

In the limited number of patients relapsing after FD I+V, subsequent treatment with ibrutinib-based regimens was shown to yield durable responses with an acceptable safety profile, even in patients with high-risk genomic features.¹ Of the 61 patients with progressive disease after completion of FD I+V, 32 initiated subsequent treatment with single-agent ibrutinib (n=25) or FD I+V (n=7).¹ With a median 21.9 months treatment on single-agent ibrutinib, 86 percent of patients achieved an overall response of partial response or better. With a median 13.8 months retreatment with FD I+V, the overall response rate (ORR) was 71 percent.¹

At longer follow-up, 18 second malignancies occurred in 13 patients and overall, no new safety signals were observed for FD I+V since the previous analysis.¹ Adverse events (AEs) during subsequent treatment were consistent with the known safety profiles for single-agent ibrutinib and I+V.¹ The most common AEs during retreatment with ibrutinib-based regimens, occurring in ≥10 percent of patients with single-agent ibrutinib or ≥2 patients treated with I+V, included diarrhoea, hypertension, pyrexia, upper respiratory tract infection and nausea, with serious AEs reported in five patients.¹

Results from six-year time to next treatment extrapolation curve for Phase 3 GLOW study

The most recently reported data on long-term evidence regarding the duration of therapeutic effect associated with FD I+V in patients with previously untreated CLL includes 57 months of follow up.² An extrapolation beyond the available time-to-next-treatment (TTNT) data was performed to estimate the number of patients who would be free from subsequent therapy after six years, with findings presented during a poster presentation at EHA (Poster #P699).² The extrapolation indicates that at six years, approximately 87 percent of patients treated with the FD I+V are unlikely to require a second line treatment.² These findings suggest the possibility of a long treatment-free period for patients with CLL, treated with the FD I+V regimen in the first-line setting.²

“Ibrutinib is the only Bruton’s tyrosine kinase inhibitor available as both a fixed duration and continuous treatment for chronic lymphocytic leukaemia and is the most comprehensively studied medicine in its class,” said Edmond Chan, MBChB, M.D. (Res), EMEA Therapeutic Area Lead Haematology, Johnson & Johnson Innovative Medicine. “The latest data presented at EHA reinforce our commitment to advancing patient care through innovative therapies, such as ibrutinib, that can be tailored to the evolving needs and preferences of patients.”

“At Johnson & Johnson, our ultimate goal is to eliminate blood cancer, and we are inspired by the transformative impact ibrutinib-based regimens continue to have on patient outcomes,” said Mark Wildgust, PhD, Vice President, Global Medical Affairs, Oncology, Johnson & Johnson Innovative Medicine. “Nearly 300,000 patients worldwide have been treated with ibrutinib, and latest findings demonstrate that patients with CLL experience deep and durable responses that translate into long treatment-free periods, with the fixed duration regimen.”

About CAPTIVATE

The Phase 2 CAPTIVATE study (NCT02910583) evaluated previously untreated adult patients with CLL, who were 71 years or younger, including patients with high-risk disease, in two cohorts: an MRD-guided cohort (n=43; median age, 58 years) and an FD cohort (n=159; median age, 60 years).¹^,³^,⁴ Patients in the FD cohort received three cycles of ibrutinib lead-in followed by 12 cycles of I+V (oral ibrutinib [420 mg/d]; oral venetoclax [five-week ramp-up to 400 mg/d]) and the primary endpoint was complete remission rate.³ In the MRD cohort, after completion of 3 cycles ibrutinib lead-in followed by 12 cycles I+V, patients with confirmed uMRD were randomly assigned to double-blind treatment with placebo, or continuous ibrutinib.³ The primary endpoint was one-year disease-free survival.³

About the GLOW study

The GLOW study (NCT03462719) is a randomised, open-label, Phase 3 trial that evaluated the efficacy and safety of first-line, FD I+V versus chlorambucil plus obinutuzumab in adult patients with CLL who are (a) ≥65 years old, or (b) 18-64 years old with a Cumulative Illness Rating Scale score of greater than six or creatinine clearance less than 70 mL/min, who had active disease requiring treatment per the International Workshop on CLL criteria.⁵

About the 6-year TTNT extrapolation curve for the GLOW study

The six-year extrapolation was produced by applying survival distribution functions to the TTNT Kaplan-Meier data of I+V from GLOW (where TTNT was defined as time to subsequent treatment).² Survival distributions describe the probability of not experiencing an event (i.e., start of subsequent anti-cancer therapy) by time.² Exponential, Weibull, Gompertz, log-logistic, log-normal, Gamma and Generalized Gamma parametric models were applied for this analysis, in line with National Institute for Health and Care Excellence (NICE) Technical Decision Support Unit recommendation.² For each distribution, the fit to observed data was assessed by the Akaike Information Criterion (AIC) and Bayes Information Criterion (BIC).² When assessing which distribution best fits the data, AIC and BIC criteria were used as well as visual inspection.² Extrapolation was performed using data available at the time of analysis (46-month follow-up).²

About Ibrutinib

Ibrutinib is a once-daily oral medication that is jointly developed and commercialised by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company.⁶ Ibrutinib blocks the Bruton’s tyrosine kinase (BTK) protein, which is needed by normal and abnormal B-cells, including specific cancer cells, to multiply and spread.⁷ By blocking BTK, ibrutinib may help move abnormal B-cells out of their nourishing environments and inhibits their proliferation.⁸
Ibrutinib is approved in more than 100 countries and has been used to treat almost 300,000 patients worldwide.⁹ There are more than 50 company-sponsored clinical trials, including 18 Phase 3 studies, over 11 years evaluating the efficacy and safety of ibrutinib.⁵^,¹⁰ In October 2021, ibrutinib was added to the World Health Organization’s Model Lists of Essential Medicines (EML), which refers to medicines that address global health priorities and which should be available and affordable for all.¹¹

Ibrutinib was first approved by the European Commission (EC) in 2014, and approved indications to date include⁵:

As a single agent or in combination with rituximab or obinutuzumab or venetoclax for the treatment of adult patients with previously untreated CLL
As a single agent or in combination with bendamustine and rituximab (BR) for the treatment of adult patients with CLL who have received at least one prior therapy
As a single agent for the treatment of adult patients with relapsed or refractory (RR) mantle cell lymphoma (MCL)
As a single agent for the treatment of adult patients with Waldenström’s macroglobulinaemia (WM) who have received at least one prior therapy, or in first line treatment for patients unsuitable for chemo-immunotherapy. In combination with rituximab for the treatment of adult patients with WM

For a full list of adverse events and information on dosage and administration, contraindications and other precautions when using ibrutinib please refer to the Summary of Product Characteristics.

About Chronic Lymphocytic Leukaemia
CLL is typically a slow-growing blood cancer of the white blood cells.¹² The overall incidence of CLL in Europe is approximately 4.92 cases per 100,000 persons per year and it is about 1.5 times more common in men than in women.¹³ CLL is predominantly a disease of the elderly, with a median age of 72 years at diagnosis.¹⁴ While patient outcomes have dramatically improved in the last few decades, the disease is still characterised by consecutive episodes of disease progression and the need for therapy.¹⁵ Patients are often prescribed multiple lines of therapy as they relapse or become resistant to treatments.¹⁶

About Johnson & Johnson
At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity.

Learn more at https://www.jnj.com/ or at www.janssen.com/johnson-johnson-innovative-medicine. Janssen Pharmaceutica NV, Janssen Research & Development, LLC, Janssen Biotech, Inc., Janssen-Cilag International NV, Janssen-Cilag Limited and Janssen Global Services, LLC are Johnson & Johnson companies.

^‡Dr Ghia has provided consulting, advisory, and speaking services to Johnson & Johnson; he has not been paid for any media work.

Cautions Concerning Forward-Looking Statements

This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of ibrutinib. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Pharmaceutica NV, Janssen Research & Development, LLC, Janssen Biotech, Inc., Janssen-Cilag International NV, Janssen-Cilag Limited, Janssen Global Services, LLC and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson’s Annual Report on Form 10-K for the fiscal year ended December 31, 2023, including in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in Johnson & Johnson’s subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of Janssen Pharmaceutica NV, Janssen Research & Development, LLC, Janssen Biotech, Inc., Janssen-Cilag International NV, Janssen-Cilag Limited, Janssen Global Services, LLC nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.

References

¹ Jacobs et al., Outcomes in High-risk Subgroups After Fixed-Duration Ibrutinib + Venetoclax for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Up To 5.5 years of Follow-up in the Phase 2 CAPTIVATE Study. Poster presentation at 2024 European Hematology Association (EHA) Hybrid Congress; June 13–16, 2024. P675
² Osorio Prendes et al., 6-Year Time To Next Treatment (Ttnt) Extrapolation Curve For Glow Study: First-Line Ibrutinib + Venetoclax (I+V) Offers Long Treatment-Free Period For Elderly/Unfit Cll Patients. Presented at 2024 European Hematology Association Hybrid Congress. Poster #P699
³ ClinicalTrials.gov. Ibrutinib Plus Venetoclax in Subjects With Treatment-naive Chronic Lymphocytic Leukemia /Small Lymphocytic Lymphoma (CLL/SLL) (CAPTIVATE). Available at: https://clinicaltrials.gov/ct2/show/NCT02910583. Last accessed: June 2024
⁴ Ghia P, et al. Fixed-duration ibrutinib + venetoclax for first-line treatment of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): up to 5 years of follow-up from the FD cohort of the phase 2 CAPTIVATE study. 2023 American Society of Hematology Annual Meeting. December 10, 2023
⁵ ClinicalTrials.gov A Study of the Combination of Ibrutinib Plus Venetoclax Versus Chlorambucil Plus Obinutuzumab for the First-line Treatment of -Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) (GLOW). Available at: https://clinicaltrials.gov/study/NCT03462719. Last accessed: June 2024
⁶ European Medicines Agency. IMBRUVICA Summary of Product Characteristics. September 2023. Available at: https.//www.ema.europa.eu/en/documents/product-information/imbruvica-epar-product-information_en.pdf. Last accessed: June 2024.
⁷ Turetsky A, et al. Single cell imaging of Bruton’s tyrosine kinase using an irreversible inhibitor. Sci Rep. 2014;4:4782.
⁸ de Rooij MF, et al. The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia. Blood. 2012. 119(11):2590-2594
⁹ J&J Data on File (RF-419273). Global number of cumulative patients treated with Ibrutinib since launch. June 2024
¹⁰ Pollyea DA, et al. A Phase I Dose Escalation Study of the Btk Inhibitor PCI-32765 in Relapsed and Refractory B Cell Non-Hodgkin Lymphoma and Use of a Novel Fluorescent Probe Pharmacodynamic Assay. Blood. 2009. 114(22): 3713
¹¹ World Health Organization. WHO prioritizes access to diabetes and cancer treatments in new Essential Medicines Lists. Available at: https://www.who.int/news/item/01-10-2021-who-prioritizes-access-to-diabetes-and-cancer-treatments-in-new-essential-medicines-lists. Last accessed: June 2024.
¹² American Cancer Society. What is chronic lymphocytic leukemia? Available at:https://www.cancer.org/cancer/chronic-lymphocytic-leukemia/about/what-is-cll.html. Last accessed: June 2024.
¹³ Sant M, et al. Incidence of hematologic malignancies in Europe by morphologic subtype: results of the HAEMACARE project. Blood. 2010. 116:3724–34.
¹⁴ Eichhorst B, et al. Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up Ann Oncol. 2021;32(1):23-33.
¹⁵ Moreno C. Standard treatment approaches for relapsed/refractory chronic lymphocytic leukemia after frontline chemoimmunotherapy. Hematology Am Soc Hematol Educ Program. 2020;2020:33-40.
¹⁶ Bewarder M, et al. Current Treatment Options in CLL. Cancers (Basel). 2021;13(10):2468

Editas Medicine Reports New Safety and Efficacy Data from the RUBY Trial of Reni-cel in 18 Patients with Sickle Cell Disease | Presented at the European Hematology Association (EHA) Annual Congress

June 14, 2024

Editas Medicine, Inc. (Nasdaq: EDIT), a clinical-stage genome editing company, today announced new safety and efficacy data in 18 patients living with sickle cell disease (SCD) treated with renizgamglogene autogedtemcel (reni-cel; formerly known as EDIT-301) in the Phase 1/2/3 RUBY clinical trial. Reni-cel, the first investigational AsCas12a gene-edited cell therapy medicine, is being studied in the RUBY trial as a potential one-time, durable medicine for people living with severe SCD. The data will be presented in an oral presentation at the European Hematology Association (EHA) Hybrid Congress in Madrid, Spain and via livestream, on Saturday, June 15 at 11:30 a.m. CEST (5:30 a.m. EDT).

In the RUBY trial to date, reni-cel was well-tolerated and continues to demonstrate a safety profile consistent with myeloablative conditioning with busulfan and autologous hematopoietic stem cell transplant by all patients (N=18). Since treatment with reni-cel, patients have been free of vaso-occlusive events (VOEs) (N=18) for up to 22.8 months of follow-up. Patients had early normalization of total hemoglobin (Hb) with a mean within the normal range at >14 g/dL and rapid and sustained improvements in fetal hemoglobin (HbF) well above levels of >40%. Patients in the RUBY trial underwent a median of 2.0 apheresis and mobilization cycles (min: 1.0, max: 4.0).

“These data confirm the observations from our prior clinical readouts and further support our belief that reni-cel has the potential to be a best-in-class and clinically differentiated, one-time, durable medicine that can provide life-changing clinical benefits to patients,” said Baisong Mei, M.D., Ph.D., Chief Medical Officer, Editas Medicine. “Importantly, we continue to make significant progress in the development of reni-cel. In the RUBY trial, we have now dosed more than 20 patients, completed adult cohort enrollment, and opened and enrolled patients in the adolescent cohort. I would like to thank the participants, their families and caregivers, clinicians, and colleagues at collaborating institutions that contribute to the RUBY trial.”

“I am encouraged by these results from the RUBY trial, demonstrating this investigational gene editing medicine has been well-tolerated and shows promising efficacy for people living with sickle cell disease. Treatment with reni-cel showed a favorable safety profile and promising preliminary efficacy, supporting further investigation as a differentiated gene-edited medicine for patients with SCD. We look forward to continuing to evaluate its effectiveness on this patient population in need of treatment options,” said Rabi Hanna, M.D., Chairman of the Division of Pediatric Hematology Oncology and Blood and Marrow Transplantation at Cleveland Clinic Children’s, and the RUBY presenting investigator.

Efficacy of reni-cel in Patients with Severe Sickle Cell Disease
All patients (N=18) are free of VOEs since reni-cel infusion with follow-up ranging from 2.4 to 22.8 months.

Reni-cel treatment drives early, robust increases and sustained levels of total Hb and HbF. Across patients with ≥6 months follow-up, at month 6, the mean (standard deviation; SD) total Hb was 14.3 g/dL (2.1 g/dL) (n=9) with a mean (SD) HbF of 48.5% (3.7%) (n=10).

The mean percentage of F-cells increased early and were sustained at >90% from month 4 through subsequent follow-ups for all patients with ≥4 months follow-up (n=12).

Mean corpuscular fetal hemoglobin (MCH-F) of HbF-containing red cells (F-cells) was sustained above the anti-sickling threshold of 10 pg/F-cell by month 3 after reni-cel infusion for all patients with ≥3 months follow-up (n=14).

All patients in the RUBY trial showed sustained high levels of editing in the HBG1 and HBG2 promoter regions.

Markers of hemolysis have been normalized or improved in patients treated with reni-cel.

Safety of reni-cel in Patients with Severe Sickle Cell Disease: Reni-cel was well-tolerated and demonstrated a safety profile consistent with myeloablative conditioning with busulfan and autologous hematopoietic stem cell transplant by all evaluated RUBY trial patients (N=18).

After reni-cel infusion, all patients (N=18) demonstrated successful neutrophil and platelet engraftment. Neutrophil engraftment occurred at a median of 23 days (min: 15 days, max: 29 days), and platelet engraftment occurred at a median of 24 days (min: 18 days, max: 51 days).

No serious adverse events (SAEs) related to reni-cel treatment in the RUBY trial have been reported.

EHA Presentations
In addition to the RUBY oral presentation, Editas will also present data from the EdiTHAL clinical trial of reni-cel for the treatment of transfusion-dependent beta thalassemia in a poster presentation on Friday, June 14.

RUBY Oral Presentation Details:
Title: Reni-cel, the first AsCas12a gene-edited cell therapy, led to hemoglobin normalization and increased fetal hemoglobin in severe sickle cell disease patients in an interim analysis of the RUBY trial
Presenting Author: Rabi Hanna, M.D., Department of Pediatric Hematology Oncology and Blood and Marrow Transplantation, Cleveland Clinic Children’s, Cleveland, OH, United States
Date/Time: Saturday, June 15, 2024, 11:30 a.m. – 12:45 p.m. CEST/ 5:30 – 6:45 a.m. EDT
Location: Hall Velasquez, IFEMA MADRID Recinto Ferial (Fairgrounds)
Session: s425 Gene therapy, cellular immunotherapy and vaccination – Clinical

EdiTHAL Poster Presentation Details:
Title: Reni-cel, the first AsCas12a gene-edited cell therapy, shows promising preliminary results in key clinical outcomes in transfusion-dependent beta thalassemia patients treated in the EdiThal trial
Presenting Author: Haydar Frangoul, M.D., M.S., Medical Director, Sarah Cannon Pediatric Hematology/Oncology & Cellular Therapy at TriStar Centennial, Nashville, TN, United States
Date/Time: Friday, June 14, 2024, 6:00 – 7:00 p.m. CEST / Noon – 1:00 p.m. EDT
Location: Hall 7, IFEMA MADRID Recinto Ferial (Fairgrounds)
Session: Poster Session

The abstracts can be accessed on the EHA website and the presentations can be accessed on the Editas Medicine website in the posters and presentations section.

Reni-cel is currently being investigated in a clinical study in patients with severe sickle cell disease (RUBY trial, NCT04853576) and transfusion-dependent beta thalassemia (EDITHAL trial, NCT05444894). In addition to the clinical data update from the RUBY and EdiTHAL trials at EHA, the Company will present a further clinical update from both trials by year-end 2024.

About renizgamglogene autogedtemcel (reni-cel)
Reni-cel, formerly known as EDIT-301, is an experimental gene editing medicine under investigation for the treatment of severe sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT). Reni-cel consists of patient-derived CD34+ hematopoietic stem and progenitor cells edited at the gamma globin gene (HBG1 and HBG2) promoters, where naturally occurring fetal hemoglobin (HbF) inducing mutations reside, by AsCas12a, a novel, proprietary, highly efficient, and specific gene editing nuclease. Red blood cells derived from reni-cel CD34+ cells demonstrate a sustained increase in fetal hemoglobin production, which has the potential to provide a one-time, durable treatment benefit for people living with severe SCD and TDT.

About the RUBY Trial: The RUBY trial is a single-arm, open-label, multi-center Phase 1/2/3 study designed to assess the safety and efficacy of reni-cel in patients with severe sickle cell disease. Enrolled patients will receive a single administration of reni-cel. The RUBY trial marks the first time AsCas12a was used to successfully edit human cells in a clinical trial. Additional details are available on www.clinicaltrials.gov (NCT04853576).

About the EdiTHAL Trial: The EdiTHAL trial is a single-arm, open label, multi-center Phase 1/2 study designed to assess the safety and efficacy of reni-cel in patients with transfusion-dependent beta thalassemia. Patients will receive a single administration of reni-cel. Additional details are available on www.clinicaltrials.gov (NCT05444894).

Innovent Biologics Delivers Oral Presentation on Clinical Data of IBI363 (First-in-class PD-1/IL-2α-bias Bispecific Antibody Fusion Protein) in Advanced Non-small Cell Lung Cancer and Other Solid Tumors at the 2024 ESMO Virtual Plenary

June 14, 2024

Innovent Biologics, Inc. (“Innovent”) (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, autoimmune, metabolic, ophthalmology and other major diseases, announced that clinical data of IBI363 (first-in-class PD-1/IL-2α-bias bispecific antibody fusion protein) in advanced solid tumors are presented at the 2024 ESMO Virtual Plenary (ClinicalTrials.gov, NCT04085185).

Dr. Hui Zhou, Senior Vice President of Innovent, stated: “IBI363, as a first-in-class molecule, represents Innovent’s continuous innovation and advancement in the immunotherapy field. Starting from molecular design, the unique approach of α bias with β and γ attenuated were creatively adopted, which greatly improved the therapeutic window of IL-2. Meanwhile, through the specific traction of PD-1, tumor-specific T cells expressing both PD-1 and CD25 can be selectively stimulated and amplified, thus exerting anti-tumor effects. IBI363 has demonstrated excellent druggability with antibody-like pharmacokinetics (IgG-like PK) and low immunogenicity. On top of the preliminary data reported at ASCO, we presented more informative data at the ESMO virtual plenary. Especially in the IO-treated squamous NSCLC, IBI363 has demonstrated strong anti-tumor effects, which could potentially be the next breakthrough in this area. Moreover, a promising efficacy signal was shown in IO-naïve mucosal melanoma, a relatively ‘cold’ tumor, which brings us great confidence in the next step to expand the IO-naïve population, and also indicates the broad application potential of IBI363.”

First-in-class PD-1/IL-2α-bias bispecific antibody fusion protein IBI363 in patients with advanced solid tumors: Results from Phase 1 study

This Phase 1a/1b Study was conducted to evaluate the safety, tolerability and preliminary efficacy of IBI363 in subjects with advanced solid tumors.

Over 300 subjects received IBI363 monotherapy treatment, unprecedented dosing level compared with traditional IL-2 therapy, with good tolerability and safety

As of the data cutoff date (Apr 16, 2024), 347 subjects with advanced solid tumors received IBI363 monotherapy (0.2μg/kg QW~3mg/kg Q3W). The tumor types included NSCLC (N=100), melanoma (N=89), colorectal cancer (N=102) and others (N=56). 81.8% of subjects had 2 or more lines of prior systemic therapy. In patients with solid tumors other than CRC (N=245), 84.1% received prior immunotherapy.
As for safety, the most common treatment related adverse events (TRAEs) were arthralgia, anaemia, hyperthyroidism and hypothyroidism. The total incidence of TRAEs ≥ grade 3 was 23.9%. Immune related adverse events (irAEs) ≥ grade 3 occurred in 10.4% of subjects. In the 38 subjects of 3mg/kg Q3W dose group, 13.2% had TRAEs ≥ grade 3, the safety profile was similar to that of the total population, and no new safety signals were identified.

Broad anti-tumor activity and applicability across tumor types, dose-dependent efficacy observed as dose reached 3mg/kg

As for efficacy, 300 subjects received IBI363 ≥0.1mg/kg and had at least one post-baseline tumor assessment. 3 subjects achieved complete response (CR) and 49 subjects had partial response (PR). As of the data cutoff date, 38 responders are still free of disease progression (PD). The duration of response (DoR) was immature. In 204 IO-treated subjects, the ORR was 17.6%.
In 15 subjects who received IBI363 3mg/kg and had at least one post-baseline tumor assessment, the ORR was 46.7% and DCR was 80.0%.

Promising efficacy signals in driver gene wild-type non-small cell lung cancer

– 70 subjects received IBI363 ≥0.3mg/kg and had at least one post-baseline tumor assessment. 77% of them had 2 or more lines of prior systemic therapy, and only 1 subject was IO-naïve. The overall ORR was 27.1%, and DCR was 72.9%.

– In the 37 subjects with squamous cell carcinoma (36 received prior PD-(L)1 treatment, 1 received prior TCE treatment), 13 achieved PR. The ORR was 35.1%, and DCR was 75.7%. As of the data cutoff date, the median follow up time was 5.7 months and the median PFS was 5.5 months (95% CI, 3.2-6.9). 11 of 13 responders are free of disease progression.

– A total of 9 NSCLC subjects (8 received prior PD-(L)1 treatment, 1 received prior TCE treatment) received IBI363 at 3mg/kg Q3W and had at least one post-baseline tumor assessment, including 6 squamous and 3 driver gene wild-type adeno NSCLC. All of the 6 patients with squamous NSCLC and 1 patient with adeno NSCLC achieved PR. The ORR was 100% and 33.3%, respectively, and the DCR were both 100%.

Promising efficacy signals in IO-treated melanoma and IO-naïve mucosal melanoma

– 37 IO-treated melanoma subjects received IBI363 1mg/kg and had at least one post-baseline tumor assessment. There were 11 responders, including 1 CR and 10 PR. The ORR and DCR was 29.7% and 73.0%, respectively.

– In 8 IO-naïve mucosal melanoma subjects, 1 patient achieved CR and 5 patients had PR. The ORR was 75.0%, and DCR was 100%.

As IBI363 has shown encouraging efficacy signals and good tolerability, this study is continuing to further explore the anti-tumor activity of IBI363 in NSCLC, melanoma and other tumors. Relevant data and analysis results will be updated in future academic conferences or journals.

Professor Xueli Bai, The First Affiliated Hospital, School of Medicine, Zhejiang University, stated:

“Lung cancer is the leading cause of cancer death worldwide, of which non-small cell lung cancer accounts for about 80%^[1]. In recent years, PD-1/PD-L1 inhibitors have shown promising efficacy in non-small cell lung cancer. However, most patients developed primary or secondary resistance to immune checkpoint inhibitors after treatment. IO-failed patients with NSCLC always suffer from a lack of effective treatment, and chemotherapy such as docetaxel elicits an ORR of only about 10% and a median PFS of less than 4 months^[2]. As an important cytokine activating tumor-specific CD8+T cells, IL-2 is complementary to immune checkpoint inhibitors in MOA. The combination of PD-1 and IL-2 may reverse the exhaustion of tumor-specific CD8+ T cells, thereby overcoming immune resistance. As a PD-1/IL-2^α-bias bispecific molecule, IBI363 showed promising antitumor activity in IO-resistant driver gene wild-type NSCLC, and clinical benefits were demonstrated by both ORR and PFS. At the same time, the safety is manageable, without new safety signals at high dose level, which gives us more confidence.”

Professor Yu Chen, Fujian cancer hospital, stated:

IBI363″Melanoma is a rare tumor in China, and the majority of patients are acral or mucosal subtypes (about 60%-70%^[3]), which are not sensitive to immunotherapy. IL-2, as an important cytokine that activates tumor-specific CD8+ T cells and mechanistically complementary to immune checkpoint inhibitors, has long become a well-established target in melanoma. As a novel PD-1/IL-2^α-bias bispecific molecule, IBI363 demonstrates significantly higher response rate than the current standard of care in IO-failed melanoma, and the response is durable. Encouraging high ORR and DCR have been observed in mucosal melanoma, a subtype known to be insensitive to immunotherapy. IBI363 is well tolerated, and the toxicity is manageable. The current safety profile is similar to that of previous anti-PD-1 monoclonal antibodies. The clinical data suggest that IBI363 has great development potential in melanoma population. Clinical trials are ongoing for further confirming the clinical benefits of IBI363 in melanoma population.”

About IBI363 (First-in-class PD-1/IL-2^α-bias bispecific antibody fusion protein)

IBI363 is a First-in-class PD-1/IL-2^α-bias bispecific antibody fusion protein independently developed by Innovent Biologics, which has two functions: blocking the PD-1/PD-L1 pathway and activating the IL-2 pathway. The IL-2 arm of IBI363 was modified to retain its affinity for IL-2Rα, but weakened its binding ability to IL-2Rβ and IL-2Rγ, thereby reducing toxicity. The PD-1 binding arm can simultaneously block PD-1 and selectively deliver IL-2. Since the newly activated tumor specific T cells express both PD-1 and IL-2α, this differential strategy allows for more precise and effective targeting and activation of this T cell subpopulation. IBI363 not only showed good antitumor activity in a variety of tumor-bearing pharmacological models, but also showed outstanding efficacy in PD-1 resistance and metastasis models. Starting from the urgent clinical needs, Innovent Biologics is conducting clinical studies in China, the United States and Australia to explore the efficacy and safety of IBI363 in advanced tumors.

Sphere Fluidics Awarded Gold Accreditation by Investors in People

June 14, 2024

Sphere Fluidics, a leading provider of innovative microfluidics-based solutions for single-cell analysis and isolation, today announced that it has received the ‘We invest in people’ Gold accreditation, a prestigious award presented by Investors in People (IIP). This accolade is in recognition of the Company’s commitment to excellence in people management and continuous improvement in workplace practices.

The IIP framework is a globally-recognized standard for people management, defining what it takes to lead, support, and manage people effectively to achieve sustainable results. Presentation of the Gold accreditation signifies how Sphere Fluidics has not only met but surpassed the high standards set by IIP when assessing the Company’s practices, policies, and overall approach to investment in people. The award demonstrates an outstanding commitment to empowering employees, fostering an inclusive culture, and driving performance through effective leadership and management practices.

Sphere Fluidics has always placed a high priority on the well-being and development of its employees, understanding that a motivated and engaged workforce is essential for driving innovation and achieving strategic goals. This prestigious award is a reflection of the Company’s robust HR practices, including comprehensive professional development programs, a strong emphasis on work-life balance, and an inclusive, collaborative workplace environment.

Dale Levitzke, CEO of Sphere Fluidics, expressed his pride in the achievement:

“Receiving the Gold Investors in People Award is a significant milestone for Sphere Fluidics. It recognizes the dedication and hard work of our entire team in creating a workplace where people feel valued, supported, and empowered to reach their full potential. This award is not just a tribute to our HR practices, but a testament to our commitment to nurturing a culture of excellence and continuous improvement.”

Denise Emsden, VP of People & Organizational Development, Sphere Fluidics added: “We are extremely proud to receive this award; a reflection of the dedication to our team and desire to ensure Sphere Fluidics is a great place to work for all our employees. It’s an honor to receive this recognition of our commitment and ambition to deliver important benefits and support to our team.”

A Must-Have Medical Equipment List For Ambulatory Care Facilities

June 14, 2024

Ambulatory care services provide a great alternative to hospital admissions. Instead of spending several days in medical facilities for minor surgeries, diagnostic tests, rehabilitation, and other health concerns, patients can visit outpatient facilities and get these results on the same day.

That said, outpatient providers have made healthcare services more affordable and accessible. So much so that in 2018, over 860 million physician visits or 267 visits per 100 people were recorded by the Centers for Disease Control and Prevention’s (CDC) National Ambulatory Medical Care Survey.

A few years prior, the Bureau of Labor Statistics (BLS) projected ambulatory services sector growth to surpass 40% from 2014 to 2024— recognizing the vast opportunities and demand for outpatient care. Indeed, the BLS recorded over 665,000 private and government-operated ambulatory care facilities as of the last quarter of 2021.

Whether you’re a healthcare professional planning to work or open an ambulatory care center, it’s crucial to know the cornerstones of ambulatory care. This article discusses the basics of the sector and the essential list of equipment you must get from reputable distributors like CIA Medical and similar firms. In addition, we suggest you visit Med-Get.com– an online marketplace where you buy new and used medical equipment and supplies.

What is ambulatory care?

Ambulatory care refers to any medical service or procedure performed outside the hospital without needing admission. That said, it’s also known as outpatient care and covers several healthcare applications divided into these categories:

Primary healthcare services cover basic care and preventive health activities. Some examples are physician’s clinics, mental health facilities, and wellness centers, although office-based clinics may qualify depending on the facilities and staff available.
Diagnostic services are either stand-alone facilities or function with another outpatient service. Diagnostic places often require multiple imaging, blood testing, and similar pieces of screening equipment.
Urgent care service providers are either free-standing or form part of a bigger ambulatory service. These facilities cater to non-emergency issues that need attention within 24 hours, like diarrhea, accidental falls, and minor fractures, to name a few.
Treatment service facilities are healthcare centers administering same-day solutions to minor surgeries, chemotherapy, dialysis, and other forms of treatment.
Rehabilitation services involve providing post-surgical and other similar services like physical therapy. Drug and alcohol abuse centers also fall under this category.
Specialty care services cater to the healthcare needs of a specific population or focus on chronic diseases, including pediatric, geriatric, and oncology centers. These facilities often utilize the latest medical technologies and equipment.
Virtual healthcare services pertain to telemedicine and other healthcare services delivered digitally. For instance, patients can discuss their concerns through video chat to get an electronic prescription. Physicians can also contact other doctors for record retrieval and case discussions.

As of 2020, there were 6,093 hospitals in the country handling over 33.3 million total admissions, according to the latest survey of the American Hospital Association. With 331 million people in the same period, one hospital caters to over 54,000 individuals.

COVID-19 infections have aggravated the challenges in the healthcare sector. As the year opened, roughly 14% of U.S. hospitals reported critical workforce shortages. Ambulatory care services, including telehealth, specialty, urgent, and diagnostic services, have helped ease the situation.

Essential medical equipment list for ambulatory care services

Outpatient care encompasses several applications and can be done in various settings, including doctor’s clinics, specialty treatment centers, rehabilitation facilities, and diagnostic laboratories. Moreover, some of the functions discussed above can overlap, depending on the facility’s target client and business model. Regardless, a facility’s medical equipment list must align with the services they offer.

Below is the list of must-haves for ambulatory care service providers, classified into different purposes.

1. Primary care equipment

A clinic must possess the following medical devices to allow doctors to check their patient’s health and wellness status easily:

Adjustable patient table or consultation area
An aneroid or digital blood pressure monitor
Audiometer
Eye chart
Weighing scale
Height chart
Thermometers
Pulse oximeter
Stethoscope
Specialized lighting

2. Diagnostic and laboratory equipment

Ambulatory diagnostic services must be equipped with the right tools based on their services. The following supplies help physicians make more accurate diagnoses:

Chemistry analyzers
Centrifuge
Computerized tomography (CT) scanner
Colposcopes
Differential counters
Deoxyribonucleic acid (DNA) analyzers
Electrocardiogram (ECG) unit
Glucose analyzers
Hematology analyzers
Histology and cytology equipment
Immunoassay analyzers
Magnetic Resonance Imaging (MRI)
Microscope
Nuclear cameras
Ophthalmoscopes
Otoscopes
Point-of-care test analyzers
Incentive spirometer
Ultrasound machine
Urine analyzers
X-ray machine

Besides this list of medical equipment, ambulatory care providers must also have storage options to retain the integrity of different samples and specimens, such as biomedical freezers and refrigerators.

3. Supplies for minor surgery and other procedures

Ambulatory care services may sometimes require minor surgeries, wound management, and vaccinations. Ensure that you can handle these requirements by keeping these basic items in hand:

Antiseptic wipes or fluids
Chemotherapy pumps
Dialysis machine
Medical gauze for dressing and bandaging
Forceps
Cotton pads, buds, and swabs
Hypodermic needles
Needle holders
Paper towels
Scissors
Tissues
Tweezers

A piece of sterilizing equipment called an autoclave is also a must-have in clinics to prevent the spread of viruses, bacteria, and other disease-causing microorganisms. These devices can disinfect medical tools using high temperatures and pressures.

4. Emergency equipment

Because healthcare costs remain prohibitive to some patients, a few may decide to consult with a doctor when it’s too late. In such instances, a patient may need to be rushed to the emergency room for proper treatment. As a healthcare provider, taking the necessary steps to extend a patient’s life is vital.

These tools may help you provide much-needed emergency care while waiting for a hospital transfer:

Aspirators
Automated External Defibrillator (AED)
Oxygen canisters and masks
Resuscitation bags
Airway suction units
Foil blankets
Spinal board
Ventilators

An AED is essential in clinics and ambulatory facilities, and areas where people congregate, such as malls. According to a 2018 study done by Johns Hopkins University and funded by the National Institutes of Health, over 18,000 Americans suffer from cardiac arrest outside hospitals and in public places. The good news is that 1,700 lives were saved through bystanders’ use of readily available AED.

5. Protective equipment

The COVID-19 virus has forced healthcare workers to exercise extreme caution in administering tests, providing care, and performing other procedures on a patient. Besides frequent disinfection, wearing appropriate personal protective equipment (PPE) is necessary.

The American Association of Pediatricians and the CDC recommend the following basic protective equipment:

Face covering
Masks
Disinfectants (i.e., hand sanitizer, alcohol, etc.)
N95 respirators
Gloves
PPE suit
Goggles

PPE suits and face shield use may have been suspended in some hospital settings. However, for workers in the ambulatory care sector, face masks, shields, and gloves remain mandatory in general. These items act as a barrier, preventing blood, fluids, and other secretions from getting into the membranes and cavities of a medical worker.

Concluding thoughts

Ambulatory care services offer cost-effective and fast solutions to patients in non-emergency situations. They’re often the first choice in accessing laboratory, diagnostic, and basic health procedures.

By procuring some or most of the essential medical equipment listed above, ambulatory care facilities strengthen their capacity to provide safe, reliable, and continuous patient access—reducing the impact of costly and overburdened hospitals.

Opthea Limited Successfully Completes Placement and Institutional Component of Entitlement Offer Raising A$171.5 million (US$113.2m¹)

June 13, 2024

Opthea Limited (ASX/NASDAQ: OPT, “Opthea”, the “Company”), a clinical-stage biopharmaceutical company developing novel therapies to treat highly prevalent and progressive retinal diseases, including wet age-related macular degeneration (wet AMD), today announced the successful completion of the institutional component of the capital raising announced on Wednesday, 12 June 2024.

The non-underwritten institutional placement (Placement) and the institutional component (Institutional Entitlement Offer) of the partially underwritten 1 for 1.22 pro-rata accelerated non-renounceable entitlement offer (Entitlement Offer) together raised approximately A$171.5 million (US$113.2m¹). The Institutional Entitlement Offer alone raised approximately A$161.5 million. Eligible institutional shareholders took up approximately 61.4% of their entitlements with the shortfall placed to both new and existing institutional shareholders and to the underwriter.

Approximately 428.7 million shares will be issued under the Placement and the Institutional Entitlement Offer (New Shares) at an offer price of A$0.40 per New Share. Of this, the underwriter will be issued approximately 55.4 million shares under the Institutional Entitlement Offer in accordance with the arrangements described in the Prospectus.

New Shares to be issued under the Placement and the Institutional Entitlement Offer will rank equally with existing OPT shares in all respects from the date of issue.

Settlement of New Shares issued under the Placement and Institutional Entitlement Offer is expected to occur on Thursday, 20 June 2024. The issue of those New Shares is expected to occur on Friday, 21 June 2024, with ordinary trading commencing on the same day.

“We appreciate the strong support from our shareholders, and from new investors, who share our belief that sozinibercept has the potential to transform patient outcomes with superior vision gains, which continues to be a significant unmet need in wet AMD,” said Frederic Guerard, PharmD, Chief Executive Officer of Opthea Limited. “This financing extends Opthea’s cash runway through the anticipated Phase 3 topline data readout of the COAST and ShORe pivotal trials of sozinibercept in wet AMD which are now expected in the early second quarter of calendar year 2025 and in mid-calendar year 2025, respectively. We look forward to updating you as we progress.”

As announced on Wednesday, 12 June 2024, the proceeds from the capital raising, together with cash on hand, will be used to fund the Company through the anticipated Phase 3 topline data readouts for COAST (Combination OPT-302 with Aflibercept Study), and ShORe (Study of OPT-302 in combination with Ranibizumab), which were designed to assess the safety and superior efficacy of sozinibercept in combination with standard-of-care anti-VEGF-A therapies compared to standard of care alone. The funds are also intended to be used to progress chemistry, manufacturing, and controls (CMC) activities, Biologics License Application (BLA) preparations for FDA approval, and for general corporate purposes.

Retail Entitlement Offer

Eligible shareholders who have a registered address in Australia or New Zealand on the register as at 7:00 pm (Melbourne time) on the Friday, 14 June 2024 Record Date and who were not invited to participate in the Institutional Entitlement Offer will be invited to participate in the retail component of the Entitlement Offer (Retail Entitlement Offer) at the same Offer Price and offer ratio as under the Institutional Entitlement Offer.

The Retail Entitlement Offer is expected to open on Wednesday, 19 June 2024, and close at 5:00pm (Melbourne time) on Wednesday, 10 July 2024.

The Retail Entitlement Offer will be made under the Prospectus. The Prospectus was lodged with ASIC and released on ASX on Wednesday, 12 June 2024 and will be dispatched to eligible retail shareholders, along with personalized application forms on Wednesday, 19 June 2024. The Prospectus provides details of how to participate in the Retail Entitlement Offer. Eligible retail shareholders may opt to take up all, part or none of their entitlement. Eligible retail shareholders will also have the opportunity to apply for and be allocated additional New Shares up to 25% of their entitlement (subject to scale back at the sole discretion of Opthea) (Top-Up Facility).

Opthea may (in its absolute discretion) extend the Retail Entitlement Offer to any institutional shareholder that was eligible to, but was not invited to participate in, the Institutional Entitlement Offer (subject to compliance with relevant laws).

The Retail Entitlement Offer is fully underwritten. The underwriting is subject to the terms and conditions of the Underwriting Agreement, which are summarized in the Investor Presentation and Prospectus. The Retail Entitlement is additionally to raise approximately A$55.9 million (US$36.9m¹).

New Options

Participants in the Placement and Entitlement Offer will also be offered one (1) option, each exercisable at A$1.00 per option and expiring on 30 June 2026 (New Options), for every three (3) New Shares subscribed under the Placement and Entitlement Offer. The offer of New Options is made under the Prospectus. No additional consideration is payable in respect of the New Options.

All New Options are expected to be issued upon allotment of the New Shares under the Retail Entitlement Offer and, subject to satisfying spread requirements set out in ASX Listing Rule 2.5, condition 6, the Options are intended to be quoted on the ASX.

The full terms and conditions of the New Options are set out in the Prospectus. Copies of the Prospectus will be available on the ASX website and at www.opthea.com.

Timetable

The timetable below is indicative only and subject to change. The Company reserves the right to alter the dates below in its full discretion and without prior notice, subject to the ASX Listing Rules and the Corporations Act.

Item	Date
Trading Halt and announcement of the Capital Raising, lodgment of Offer Documents, including Prospectus with ASIC	Wednesday, 12 June 2024
Placement and Institutional Entitlement Offer opens	Wednesday, 12 June 2024
Placement and Institutional Entitlement Offer closes	Thursday, 13 June 2024
Announcement of completion of the Institutional Entitlement Offer and Placement, trading halt lifted, existing securities recommence trading	Friday, 14 June 2024
Record Date for Entitlement Offer	7:00pm (Melbourne time) on Friday, 14 June 2024
Despatch of Prospectus under Retail Entitlement Offer	Wednesday, 19 June 2024
Retail Entitlement Offer opens	Wednesday, 19 June 2024
Settlement of New Shares issued under the Institutional Entitlement Offer and Placement	Thursday, 20 June 2024
Allotment of New Shares issued under the Institutional Entitlement Offer and Placement	Friday, 21 June 2024
Retail Entitlement Offer closes	5:00pm (Melbourne time) on Wednesday, 10 July 2024
Announcement of results of the Retail Entitlement Offer and notification of any shortfall under the Retail Entitlement Offer	Monday, 15 July 2024
Settlement of New Shares under the Retail Entitlement Offer and any shortfall under the Retail Entitlement Offer	Tuesday, 16 July 2024
Allotment and issue of New Shares and New Options under the Retail Entitlement Offer, and New Options issued under the Institutional Entitlement Offer and Placement	Wednesday, 17 July 2024
Trading commences on a normal basis for New Shares issued under the Retail Entitlement Offer and New Options under the Entitlement Offer and Placement	Thursday, 18 July 2024
Despatch of holding statements for New Shares issued under the Retail Entitlement Offer and New Options under the Entitlement Offer and Placement	Friday, 19 July 2024

About Opthea

Opthea (ASX/NASDAQ:OPT) is a biopharmaceutical company developing novel therapies to address the unmet need in the treatment of highly prevalent and progressive retinal diseases, including wet age-related macular degeneration (wet AMD) and diabetic macular edema (DME). Opthea’s lead product candidate, sozinibercept, is being evaluated in two pivotal Phase 3 clinical trials (COAST, NCT04757636, and ShORe, NCT04757610) for use in combination with standard-of-care anti-VEGF-A monotherapies to improve overall efficacy and deliver superior vision gains compared to standard-of-care anti-VEGF-A agents. To learn more, visit our website at www.opthea.com and follow us on X and LinkedIn.

Inherent Risks of Investment in Biotechnology Companies

There are a number of inherent risks associated with the development of pharmaceutical products to a marketable stage. The lengthy clinical trial process is designed to assess the safety and efficacy of a drug prior to commercialization and a significant proportion of drugs fail one or both of these criteria. Other risks include uncertainty of patent protection and proprietary rights, whether patent applications and issued patents will offer adequate protection to enable product development, the obtaining of necessary drug regulatory authority approvals and difficulties caused by the rapid advancements in technology. Companies such as Opthea are dependent on the success of their research and development projects and on the ability to attract funding to support these activities. Investment in research and development projects cannot be assessed on the same fundamentals as trading and manufacturing enterprises. Therefore, investment in companies specializing in drug development must be regarded as highly speculative. Opthea strongly recommends that professional investment advice be sought prior to such investments.

Forward-Looking Statements

This ASX announcement contains certain forward-looking statements, including within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. The words “expect”, “believe”, “should”, “could”, “may”, “will”, “plan” and other similar expressions are intended to identify forward-looking statements. Forward-looking statements in this ASX announcement include statements regarding rapidly advancing the registrational program for sozinibercept in wet AMD, expectations regarding the pivotal growth phase of Opthea, the ability of sozinibercept to enhance vision outcomes for patients worldwide, Opthea’s expected cash runway, the expected timing for topline data readout, and the expected use of proceeds. Forward-looking statements, opinions and estimates provided in this ASX announcement are based on assumptions and contingencies which are subject to change without notice, as are statements about market and industry trends, which are based on interpretations of current conditions. Forward-looking statements are provided as a general guide only and should not be relied upon as an indication or guarantee of future performance. They involve known and unknown risks and uncertainties and other factors, many of which are beyond the control of Opthea and its directors and management and may involve significant elements of subjective judgment and assumptions as to future events that may or may not be correct. These statements may be affected by a range of variables which could cause actual results or trends to differ materially, including but not limited to future capital requirements, the completion of the capital raising, Opthea’s ability to continue as a going concern, the development, testing, production, marketing and sale of drug treatments, regulatory risk and potential loss of regulatory approvals, ongoing clinical studies to demonstrate sozinibercept’s safety, tolerability and therapeutic efficacy, additional analysis of data from Opthea’s Phase 3 clinical trials, clinical research organization, contract manufacturer; Biologics License Application preparation, corporate and labor costs, intellectual property protections, and other factors that are of a general nature which may affect the future operating and financial performance of the Company including risk factors set forth in Opthea’s Annual Report on Form 20-F filed with the U.S. Securities and Exchange Commission (the “SEC”) on September 28, 2023, Opthea’s 2024 Half Year Report included as an exhibit to the Form 6-K filed with the SEC on February 29, 2024, and other future filings with the SEC. Actual results, performance or achievement may vary materially from any projections and forward-looking statements and the assumptions on which those statements are based. Subject to any continuing obligations under applicable law or any relevant ASX listing rules, Opthea disclaims any obligation or undertaking to provide any updates or revisions to any forward-looking statements in this ASX announcement to reflect any change in expectations in relation to any forward-looking statements or any change in events, conditions or circumstances on which any such statement is based, except as otherwise required by applicable law.

Not An Offer

This ASX announcement is not a disclosure document and should not be considered as investment advice. The information contained in this ASX announcement is for information purposes only and should not be considered an offer or an invitation to acquire Company securities or any other financial products and does not and will not form part of any contract for the acquisition of New Shares.

In particular, this ASX announcement does not constitute an offer to sell, or a solicitation of any offer to buy, any securities in the United States or any other jurisdiction in which such an offer would be illegal or impermissible. The securities to be offered and sold in the Placement and Entitlement Offer have not been, and will not be, registered under the U.S. Securities Act of 1933, as amended (the “U.S. Securities Act”), or the securities laws of any state or other jurisdiction of the United States. No public offering of securities is being made in the United States. Accordingly, the securities to be offered and sold in the Placement and Entitlement Offer may only be offered and sold outside the United States in “offshore transactions” (as defined in Rule 902(h) under Regulation S of the U.S. Securities Act (“Regulation S”)) in reliance on Regulation S, unless they are offered and sold in a transaction registered under, or exempt from, or in a transaction not subject to, the registration requirements of, the U.S. Securities Act and applicable U.S. state securities laws.

Authorized for release to ASX by Frederic Guerard, CEO

InduPro Announces $85 Million Series A Financing

June 13, 2024

InduPro, Inc., a biotechnology company defining protein spatial relationships to create novel therapeutics for the treatment of cancer and autoimmune diseases, today announced an $85 million Series A financing co-led by The Column Group and Vida Ventures with participation from investors, including MRL Ventures Fund (the therapeutics-focused venture fund of Merck & Co, Inc.), Emerson Collective and Euclidean Capital. The financing will support the advancement of the first expected clinical product candidate targeting cancer tissue based on the proximity of co-targeted pairs, from preclinical development to an expected IND filing in Q4 2025 for a Phase 1 clinical trial. It will also fuel a pipeline of novel bispecific antibodies and antibody drug conjugates (ADCs) that utilizes protein proximity for identification of novel tumor selective target pairings.

Prakash Raman, Ph.D. joins as Chief Executive Officer of InduPro with more than two decades of biopharmaceutical business development and executive leadership experience, blending his scientific background, program and portfolio management and strong business development experience to lead and support biopharma companies.

InduPro therapeutically targets cell surface proteins in a variety of disease contexts by leveraging inherent or induced protein proximity. Through precise mapping of protein neighborhoods using its proprietary, high resolution proximity labeling technology, the Company is discovering novel co-target pairs that are highly selective for specific disease biology. Additionally, since protein proximity influences signals in cells that are critical for cellular health, proximity can be induced to modify cellular signaling and interactions in disease. InduPro’s approach relies on a unique discovery engine (ProXiMATE) to generate potential first-in-class and best-in-class novel therapeutic candidates across multiple indications and modalities.

“Our team is highly focused on precisely defining the spatial proximity of proteins on the surface of cells with high therapeutic potential across a broad range of indications and applications,” said Dr. Raman. “Instead of a limited subset of targets with known disease biology, we are discovering novel targets and best-in class approaches for areas of high unmet need for many cancer and autoimmune patients.”

The lead bispecific ADC program uses the Company’s Tumor Associated Proximity Antigen (TAPA) therapeutic approach to specifically target cancer tissue based on the proximity of co-targeted pairs discovered. In a separate ‘immunological synapse modulation’ approach, multi-specific antibodies are directed against targets whose induced proximity recruits and activates (or sequesters) proteins on the surface of immune cells in the treatment of autoimmune disease or immuno-oncology.

“Our approach provides unique insight into novel targets and mechanisms of biology by which to target and manipulate disease biology. This approach creates high patient impact and enables our first- and best-in class programs,” said Scott Lesley, Ph.D., President & Chief Scientific Officer. “Our ProXiMATE platform leverages deep learning analysis of protein microenvironment and membrane proteomic data to create an extensive knowledge base of highly-tuned protein proximity maps that continually generate novel and high-value tumor selective targets for ADCs and T cell engagers.”

“We are delighted that InduPro’s unique discovery engine is driven and supported by a talented team led by Prakash and will provide a strong foundation for a robust pipeline of potentially transformative therapeutics with opportunities for expansion and partnership,” said Sarah Hymowitz, Ph.D., partner at The Column Group and Board Chair of InduPro. “We look forward to collaborating with the InduPro team to bring novel and highly promising therapies to patients living with a wide range of cancers and autoimmune diseases.”

Dr. Raman previously served as President and CEO of Ribon Therapeutics, a biotech company focused on first-in-class small molecule drugs for Oncology and Immunology targeting the PARP family of enzymes. Prior to joining Ribon, Dr. Raman was a Senior Partner, Chief Business Development Officer at Flagship Pioneering, and held senior roles at Novartis for nearly 14 years, most recently as Vice President, Global Head of Novartis Institutes for Biomedical Research (NIBR) Business Development and Licensing. Dr. Raman completed his undergraduate work at the Indian Institute of Technology, Bombay, and received his Ph.D. in Organic and Medicinal Chemistry from the University of Wisconsin-Madison.

Formed in 2022 by Scientific Founder and recent Passano Award winner Chris Garcia, Ph.D., CSO Scott Lesley, Ph.D., and inventors of the protein proximity-based mapping technology, Rob Oslund Ph.D. and Niyi Fadeyi Ph.D., InduPro is led by a dedicated Board of Directors that includes Sarah Hymowitz, Ph.D., Board Chair from The Column Group, Helen Kim and Rajul Jain, M.D. from Vida Ventures, Peter Dudek, Ph.D. from MRL Ventures Fund, Rahul Ballal, Ph.D. CEO from Mediar Therapeutics, Craig Parker CEO from Surrozen, and InduPro CEO Prakash Raman, Ph.D.

Hospice Nurse with 3 Million Social Media Followers Partners with Medical Device Company

June 13, 2024

“Hospice Nurse Julie” and Hospi Corporation–the maker of the Macy Catheter–are pleased to announce their partnership.

Julie McFadden, RN is one of the leading voices working to demystify hospice and end of life care on social media. She is known as “Hospice Nurse Julie” to her sizable audience of over 3 million collective followers across Instagram, TikTok, Facebook, and YouTube.

McFadden and medical device company Hospi Corporation share the mission to reduce suffering at end-of-life. Hospi introduced the first innovation to hospice bedside care in decades when it launched the Macy Catheter. The device provides rectal access for medication and fluid administration so patients can immediately continue receiving medications when they can’t take them by mouth. Over 100,000 patients have benefited from the rapid symptom management enabled by the Macy Catheter.

Hospice Nurse Julie and Hospi work together to spread the word about how the Macy Catheter improves quality of life for hospice patients and their caregivers.

When asked about why Hospi and McFadden chose to partner with each other, Hospi CEO Igal Ladabaum said, “It was a revelation to me that people are turning to trusted online personalities even for the most intimate of healthcare topics, but after coming across Hospice Nurse Julie I understood why and I immediately knew that we needed to work together. With access to good information, patients and families can better advocate for themselves and their loved ones.”

McFadden shared, “When I first learned about the Macy Catheter, it was a no-brainer. My first thought was– Why didn’t I think of this? It’s an easy decision to partner with a product and company so aligned with my mission.”

Ladabaum further elaborated, “The Macy Catheter is basically a soft little tube that is placed in the rectum. Many people initially recoil at the thought of the rectal route. We needed the right partner in order to communicate that the Macy Catheter actually makes the rectal route comfortable and dignified.”

Julie McFadden–known as “Hospice Nurse Julie“–is a hospice nurse and social media influencer known for her compassionate and educational content on hospice care. Her social media presence has made her a trusted voice in the hospice community. She uses her platform to share valuable insights, personal stories, and educational content. Julie is also the author of “Nothing to Fear,” which offers a deeper look into her professional insights and her personal experiences in the field.

Inspira Receives 1st Ever Purchase Order for INSPIRA™ ART100 Systems in the U.S.

June 13, 2024

Inspira Technologies OXY B.H.N. Ltd. (Nasdaq: IINN, IINNW) (the “Company” or “Inspira”), a breakthrough medical technology company, today announced that is has received the first purchase order from Glo-Med Networks, Inc. (“Glo-Med”) for its INSPIRA™ ART100 systems, with the five product units expected to be shipped in the fourth quarter of 2024. The purchase order also provides for the potential purchase of an additional 20 systems, the timing of which is subject to further agreement between Inspira and Glo-Med.

The planned shipment and potential additional sales of the INSPIRA™ ART100 systems is a pivotal step in the Company’s growth model, which is primarily based on the INSPIRA™ ART (Gen 2) that is currently in development and is expected to target the $19 billion mechanical ventilator market, with its next generation cutting-edge technology designed to replace the need for mechanical ventilation. The Company plans to offer hospitals receiving the INSPIRA™ ART100 an option with special terms for the integrated HYLA™ Blood Sensor and INSPIRA™ ART (Gen 2) devices, subject to the completion of the development of those products, which are also subject to approval by regulatory entities.

Joe Hayon, Director, President and co-founder of Inspira stated: “We continue to develop the breakthrough technologies of tomorrow. The INSPIRA™ ART100, is our first and important step in building the INSPIRA market presence and position in preparation for the INSPIRA™ ART (Gen 2), which we believe has the potential to provide a new clinical solution with a potentially different intent of use for the mega life support and mechanical ventilation market.”

The Company already began the commercial manufacturing of the INSPIRA™ ART100 with the first five units planned for shipment to Glo-Med, a distributor for Inspira products in the U.S., with the devices planned for deployment in U.S. hospitals.

Inspira received FDA 510(k) clearance for its INSPIRA ART100, a Cardiopulmonary Bypass System.

The Company’s other products, including the INSPIRA ART (Gen 2) and HYLA™ blood sensor, have not yet been tested or used in humans and have not been approved by any regulatory entity.

Movano Health Applies Advanced AI through Deep Learning to Deliver Improved Accuracy of Heart Rate in Motion

June 13, 2024

Movano Health announced major advances in the accuracy of its heart rate in motion algorithm following the implementation of deep learning into the processing.

Movato Health recently released an engineering accuracy study directed by Movano Health Founder and CTO Michael Leabman, Enhanced Heart Rate in Motion Accuracy with the Evie Ring Using Advanced Deep Learning Algorithms, which demonstrates the value of deep learning integration into heart rate (HR) algorithms for improved accuracy.

“Utilizing deep learning is significantly better than standard techniques as it is the optimal solution for removing the effects of motion, eliminating the noise and motion artifacts in the optical signal,” said Leabman. “We believe that this is a first of its kind implementation and an innovation that has the potential to enhance the reliability of wearable health monitors, providing users with more accurate and consistent heart rate measurements.”

Movato Health Notes…

The study was conducted with 65 subjects, completing 7-10 sessions of various activities including sleeping, resting, walking, running, climbing stairs, working out at the gym, and swimming. Data was collected with the Evie Ring and a Polar H7 chest strap used as a control device. The results demonstrated a high correlation with the Polar H7 chest strap outputs across a diverse data set, confirming the reliable reporting of heart rate by Evie’s HR algorithm across all activities.

To overcome the challenges of measuring heart rate from PPG signals in wearables, Evie’s HR solution combines the best from the signal processing world as well as recent advances in AI-based Deep Learning.

Optimally filtering out motion artifacts and more accurately tracking heart rate through development of AI algorithms in a specific, novel Deep Learning solution.
Removing motion artifacts from the PPG signal by leveraging both PPG and 3D accelerometer data.
Enhancing the signal-to-noise ratio (SNR) through Deep Learning.

The Company plans to convert all Evie Ring algorithms including sleep, respiration, heart rate variability (HRV), and blood oxygen saturation (SpO2) through this same process.

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