Outlook Therapeutics® Announces Complete Twelve Week Efficacy and Safety Results of NORSE EIGHT Clinical Trial
Outlook Therapeutics (OTLK) has announced complete 12-week efficacy and safety results for its NORSE EIGHT clinical trial evaluating ONS-5010 in wet AMD patients. The trial demonstrated non-inferiority to ranibizumab at week 12, with ONS-5010 showing a mean 5.5 letter improvement in BCVA compared to 6.5 letters for ranibizumab.
The company plans to resubmit its Biologics License Application (BLA) in Q1 2025. While the trial didn't meet its week 8 primary endpoint, the 12-week data showed consistent improvement and comparable safety to ranibizumab. ONS-5010 has already received marketing authorization in the EU and UK, with European launch planned for first half of 2025.
Additionally, OTLK has entered into warrant inducement transactions expected to generate up to $20.4 million in gross proceeds, which will fund clinical development programs, European commercial launch, and working capital.
Outlook Therapeutics (OTLK) ha annunciato i risultati completi di efficacia e sicurezza a 12 settimane del suo trial clinico NORSE EIGHT che valuta ONS-5010 in pazienti con AMD umida. Lo studio ha dimostrato non inferiorità rispetto al ranibizumab alla settimana 12, con ONS-5010 che ha mostrato un miglioramento medio di 5.5 lettere nella BCVA rispetto a 6.5 lettere per il ranibizumab.
L'azienda prevede di ripresentare nuovamente la sua Biologics License Application (BLA) nel primo trimestre del 2025. Sebbene lo studio non abbia raggiunto il suo obiettivo primario alla settimana 8, i dati a 12 settimane hanno mostrato un miglioramento costante e una sicurezza comparabile a quella del ranibizumab. ONS-5010 ha già ricevuto l'autorizzazione alla commercializzazione nell'UE e nel Regno Unito, con un lancio europeo previsto per la prima metà del 2025.
Inoltre, OTLK ha avviato transazioni di indennizzo di warrant che si prevede genereranno fino a 20,4 milioni di dollari in proventi lordi, i quali finanzieranno i programmi di sviluppo clinico, il lancio commerciale in Europa e il capitale circolante.
Outlook Therapeutics (OTLK) ha anunciado los resultados completos de eficacia y seguridad a 12 semanas de su ensayo clínico NORSE EIGHT que evalúa ONS-5010 en pacientes con AMD húmeda. El ensayo demostró no inferioridad frente al ranibizumab a la semana 12, con ONS-5010 mostrando una mejora media de 5.5 letras en la BCVA en comparación con 6.5 letras para ranibizumab.
La empresa planea volver a presentar su Solicitud de Licencia Biológica (BLA) en el primer trimestre de 2025. Aunque el ensayo no alcanzó su objetivo primario en la semana 8, los datos a 12 semanas mostraron una mejora consistente y una seguridad comparable a la del ranibizumab. ONS-5010 ya ha recibido autorización de comercialización en la UE y el Reino Unido, con un lanzamiento europeo previsto para la primera mitad de 2025.
Adicionalmente, OTLK ha entrado en transacciones de inducción de warrants que se espera generen hasta 20.4 millones de dólares en ingresos brutos, los cuales financiarán programas de desarrollo clínico, el lanzamiento comercial en Europa y capital de trabajo.
Outlook Therapeutics (OTLK)는 습성 AMD 환자에서 ONS-5010을 평가하는 NORSE EIGHT 임상 시험의 12주 완전 효능 및 안전성 결과를 발표했습니다. 이 시험은 12주차에 ranibizumab에 비해 열등하지 않음을 보여주었습니다, ONS-5010은 ranibizumab의 6.5자에 비해 BCVA에서 평균 5.5자 개선을 보였습니다.
회사는 2025년 1분기에 생물학적 제제 라이센스 신청(BLA)을 재제출할 계획입니다. 시험이 8주차에 주요 목표를 달성하지 못했지만, 12주 데이터는 일관된 개선과 ranibizumab과의 비교 안전성을 보여주었습니다. ONS-5010은 이미 EU와 UK에서 상업화 승인을 받았으며, 2025년 상반기 유럽 출시가 예고되어 있습니다.
또한, OTLK는 최대 2040만 달러의 총 수익을 생성할 것으로 예상되는 워런트 유도 거래에 들어갔습니다, 이 자금은 임상 개발 프로그램, 유럽 상업 출범 및 운영 자본에 사용될 것입니다.
Outlook Therapeutics (OTLK) a annoncé les résultats complets de 12 semaines d'efficacité et de sécurité de son essai clinique NORSE EIGHT évaluant l'ONS-5010 chez des patients atteints d'AMD humide. L'essai a démontré une non-infériorité par rapport au ranibizumab à la semaine 12, l'ONS-5010 montrant une amélioration moyenne de 5,5 lettres en BCVA contre 6,5 lettres pour le ranibizumab.
L'entreprise prévoit de soumettre à nouveau sa demande de licence biologique (BLA) au premier trimestre 2025. Bien que l'essai n'ait pas atteint son objectif principal à 8 semaines, les données de 12 semaines ont montré une amélioration cohérente et une sécurité comparable à celle du ranibizumab. L'ONS-5010 a déjà reçu une autorisation de mise sur le marché dans l'UE et au Royaume-Uni, avec un lancement européen prévu pour la première moitié de 2025.
De plus, OTLK a engagé des transactions d'incitation par warrants qui devraient générer jusqu'à 20,4 millions de dollars de produits bruts, financant les programmes de développement clinique, le lancement commercial en Europe et le fonds de roulement.
Outlook Therapeutics (OTLK) hat die vollständigen Ergebnisse zur Wirksamkeit und Sicherheit der 12-wöchigen NORSE EIGHT-Studie veröffentlicht, die ONS-5010 bei Patienten mit feuchter AMD bewertet. Die Studie zeigte keine Unterlegenheit gegenüber Ranibizumab in Woche 12, wobei ONS-5010 eine durchschnittliche Verbesserung von 5,5 Buchstaben im BCVA im Vergleich zu 6,5 Buchstaben für Ranibizumab erzielte.
Das Unternehmen plant, im ersten Quartal 2025 seinen Antrag auf Lizenz für Biologika (BLA) erneut einzureichen. Obwohl die Studie ihr primäres Ziel in Woche 8 nicht erreicht hat, zeigten die 12-Wochen-Daten eine konsistente Verbesserung und vergleichbare Sicherheit zu Ranibizumab. ONS-5010 hat bereits eine Zulassung in der EU und im Vereinigten Königreich erhalten, mit einem geplanten europäischen Markteintritt in der ersten Hälfte von 2025.
Zusätzlich hat OTLK in Warrants-Induzierungs-Transaktionen investiert, die voraussichtlich bis zu 20,4 Millionen Dollar Bruttoerlös generieren werden, die Programme zur klinischen Entwicklung, den europäischen Markteintritt und das Betriebskapital finanzieren werden.
- Demonstrated non-inferiority to ranibizumab at week 12 in NORSE EIGHT trial
- Secured Marketing Authorization in EU and UK markets
- Raising $20.4 million through warrant inducement transaction
- European commercial launch planned for first half of 2025
- Failed to meet pre-specified non-inferiority endpoint at week 8
- BLA resubmission delayed until Q1 2025
- Warrant transaction will result in additional share dilution
Insights
The NORSE EIGHT trial results demonstrate compelling clinical evidence for ONS-5010. The 12-week data shows non-inferiority to ranibizumab with a mean difference of -1.009 BCVA letters and a confidence interval (-2.865, 0.848), meeting statistical significance (p=0.0043). The +5.5 letter improvement in the ONS-5010 arm validates its therapeutic efficacy.
The anatomical response measured by central retinal thickness shows comparable results between ONS-5010 and ranibizumab across all timepoints, with ONS-5010 achieving a -123.9 micron reduction at week 12. The safety profile aligns with previous NORSE trials, showing no cases of retinal vasculitis - a critical safety consideration for ophthalmic biologics.
The warrant inducement transaction represents a strategic capital raise of up to
The transaction's split structure, with half the warrants contingent on authorized share increase approval, indicates careful capital management while minimizing immediate dilution. The
The positive 12-week efficacy data strengthens Outlook's competitive position in the wet AMD market. With EU/UK marketing authorization already secured and planned European launch in H1 2025, ONS-5010 is positioned to capture market share from off-label bevacizumab use. The successful non-inferiority demonstration against Lucentis (ranibizumab) at 12 weeks enhances the product's commercial viability.
The timing of the BLA resubmission in Q1 2025 aligns well with commercial preparations. If approved, ONS-5010 would address the significant unmet need for an FDA-approved ophthalmic bevacizumab formulation, potentially transforming the standard of care in wet AMD treatment.
- ONS-5010 demonstrated to be non-inferior to Lucentis at 12 weeks
- BLA resubmission on track for calendar Q1 2025
- Entered into agreements for warrant inducement transaction expected to result in up to
$20.4 million in gross proceeds
ISELIN, N.J., Jan. 16, 2025 (GLOBE NEWSWIRE) -- Outlook Therapeutics, Inc. (Outlook Therapeutics, or the Company) (Nasdaq: OTLK), a biopharmaceutical company that achieved regulatory approval in the European Union and the United Kingdom for the first authorized use of an ophthalmic formulation of bevacizumab for the treatment of wet age-related macular degeneration (wet AMD), today announced it has completed the analysis of the complete 12-week safety and efficacy results for NORSE EIGHT, the second of two adequate and well controlled clinical trials evaluating ONS-5010 in wet AMD patients. ONS-5010 demonstrated noninferiority to ranibizumab at week 12 in the NORSE EIGHT trial. Based on the completed analysis of the 12-week results, Outlook Therapeutics plans to resubmit the Biologics License Application (BLA) for ONS-5010 in the first quarter of calendar 2025.
Julia A. Haller, MD, Ophthalmologist-in-Chief at Wills Eye Hospital and an Outlook Therapeutics Board member, commented, “The 3-month data from NORSE EIGHT provides additional evidence to confirm what retina specialists expected. The clinical trial continues to demonstrate that ONS-5010 injections result in immediate and sustained anatomic efficacy, with steady gains in visual acuity and reliable, consistent safety.”
The difference in the mean between ONS-5010 and ranibizumab was -1.009 best corrected visual acuity (BCVA) letters with a
| Mean change in BCVA at week 12 | Non-Inferiority | |
| ONS-5010 1.25 mg | +5.5 letters | P-value: 0.0043 |
| Ranibizumab 0.5mg | +6.5 letters |
Additionally, the change in central retinal thickness, a measure of anatomical response, was similar in both study arms at all three study timepoints.
| Mean change in central retinal thickness | |||
| Week 4 | Week 8 | Week 12 | |
| ONS-5010 1.25 mg | -106.6 microns | -117.7 microns | -123.9 microns |
| Ranibizumab 0.5mg | -108.4 microns | -120.9 microns | -127.3microns |
As previously announced, in the NORSE EIGHT trial, ONS-5010 did not meet the pre-specified non-inferiority endpoint at week 8 set forth in the special protocol assessment (SPA) with the U.S. Food and Drug Administration (FDA). However, BCVA data across all study timepoints demonstrated an improvement in vision, increasing over time, and the presence of biologic activity. Overall, in NORSE EIGHT, ONS-5010 demonstrated mean visual acuity improvements of +3.3 letters at week 4, +4.2 letters at week 8, and +5.5 letters at week 12.
Additionally, in NORSE EIGHT, ONS-5010 was generally well-tolerated with overall ocular adverse event rates comparable to ranibizumab. The safety results demonstrated across the full duration of NORSE EIGHT are consistent with previously reported safety results from the NORSE ONE, NORSE TWO, and NORSE THREE clinical trials, with no cases of retinal vasculitis reported in either study arm.
“We believe that the statistically significant 12-week results for ONS-5010 in NORSE EIGHT, combined with the complete NORSE EIGHT data set, confirms our successful NORSE TWO pivotal study and will support the resubmission of our BLA in the United States for the treatment of wet AMD,” added Lawrence Kenyon, Chief Financial Officer and Interim Chief Executive Officer of Outlook Therapeutics. “Our team continues the necessary work for the planned resubmission of our BLA in the first quarter of calendar 2025. We remain confident in the potential of ONS-5010/LYTENAVA™ to provide an important therapy for the treatment of wet AMD in place of off-label repackaged bevacizumab that has not received regulatory approval for use in retinal diseases here in the United States.”
In the European Union and the United Kingdom, ONS-5010/LYTENAVA™ (bevacizumab gamma) has already been granted Marketing Authorization. Outlook Therapeutics intends to begin launching in Europe in the first half of calendar 2025.
Warrant Inducement Transaction
The Company has entered into warrant exercise inducement offer letters (the Inducement Letters) with certain holders of existing warrants to purchase the Company’s common stock, exercisable for an aggregate of 8,146,066 shares of common stock (the Existing Warrants), pursuant to which the holders agreed to exercise their Existing Warrants at a reduced exercise price of
The gross proceeds to the Company from the exercise of the Existing Warrants are expected to be up to approximately
In consideration for the immediate exercise of the Existing Warrants for cash at the Reduced Exercise Price, holders will receive Inducement Warrants. The Inducement Warrants will be exercisable for an aggregate of up to 16,292,132 shares of Common Stock at an exercise price of
The Company intends to use the net proceeds from the exercise of the Existing Warrants to fund its ONS-5010 clinical development programs, European commercial launch of LYTENAVA™ and for working capital and general corporate purposes.
In connection with the transaction described above, BTIG, LLC served as capital markets advisor.
The Inducement Warrants and shares of common stock issuable upon exercise thereof were offered in a private placement in reliance on the exemptions provided by Section 4(a)(2) of the Securities Act of 1933, as amended (the Securities Act), and similar exemptions under applicable state laws and have not been registered under the Securities Act or applicable state securities laws. Accordingly, the Inducement Warrants and the underlying shares of common stock may not be offered or sold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Securities Act and such applicable state securities laws. As part of the transaction, the Company has agreed to file a resale registration statement on Form S-3 to register the resale of the shares of common stock underlying the Inducement Warrants.
The warrant inducement transaction with respect to an aggregate of 7,074,637 Existing Warrants for gross proceeds of
About NORSE EIGHT
NORSE EIGHT was a randomized, controlled, parallel-group, masked, non-inferiority study of newly diagnosed, wet AMD subjects randomized in a 1:1 ratio to receive 1.25 mg ONS-5010 or 0.5 mg ranibizumab intravitreal injections. Subjects received injections at day 0 (randomization), week 4, and week 8 visits, and returned for a final study visit at week 12. The primary endpoint was mean change in BCVA from baseline to week 8. For more information about the NORSE EIGHT study, visit clinicaltrials.gov and reference identifier NCT06190093.
About ONS-5010 / LYTENAVA™ (bevacizumab-vikg, bevacizumab gamma)
ONS-5010/LYTENAVA™ is an ophthalmic formulation of bevacizumab for the treatment of wet AMD. LYTENAVA™ (bevacizumab gamma) is the subject of a centralized Marketing Authorization granted by the European Commission in the European Union (EU) and Marketing Authorization granted by the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom (UK) for the treatment of wet AMD.
In the United States, ONS-5010/LYTENAVA™ (bevacizumab-vikg) is investigational.
Bevacizumab-vikg (bevacizumab gamma in the EU and UK) is a recombinant humanized monoclonal antibody (mAb) that selectively binds with high affinity to all isoforms of human vascular endothelial growth factor (VEGF) and neutralizes VEGF’s biologic activity through a steric blocking of the binding of VEGF to its receptors Flt-1 (VEGFR-1) and KDR (VEGFR-2) on the surface of endothelial cells. Following intravitreal injection, the binding of bevacizumab to VEGF prevents the interaction of VEGF with its receptors on the surface of endothelial cells, reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation in the retina.
About Outlook Therapeutics, Inc.
Outlook Therapeutics is a biopharmaceutical company focused on the development and commercialization of ONS-5010/LYTENAVA™ (bevacizumab-vikg; bevacizumab gamma), for the treatment of retina diseases, including wet AMD. LYTENAVA™ (bevacizumab gamma) is the first ophthalmic formulation of bevacizumab to receive European Commission and MHRA Marketing Authorization for the treatment of wet AMD. Outlook Therapeutics is working to initiate its commercial launch of LYTENAVA™ (bevacizumab gamma) in the EU and the UK as a treatment for wet AMD, expected in the first half of calendar 2025. In the United States, ONS-5010/LYTENAVA™ is investigational, is being evaluated in an ongoing non-inferiority study for the treatment of wet AMD, and if successful, the data may be sufficient for Outlook to resubmit a BLA to the FDA in the United States. If approved in the United States, ONS-5010/LYTENAVA™, would be the first approved ophthalmic formulation of bevacizumab for use in retinal indications, including wet AMD.
Forward-Looking Statements
This press release contains forward-looking statements. All statements other than statements of historical facts are “forward-looking statements,” including those relating to future events. In some cases, you can identify forward-looking statements by terminology such as “anticipate,” “believe,” “continue,” “expect,” “may,” “plan,” “potential,” “will,” or “would” the negative of terms like these or other comparable terminology, and other words or terms of similar meaning. These include, among others, Outlook Therapeutics’ plans for commercial launch of LYTENAVA™ in the UK and EU and timing thereof, as well as the potential to launch with a partner, expectations concerning Outlook Therapeutics’ ability to remediate or otherwise resolve deficiencies identified in the CRL issued by the FDA, plans to resubmit the BLA for ONS-5010 and the timing thereof, Outlook Therapeutics’ commercialization strategy, expectations concerning decisions of regulatory bodies and the timing thereof, the therapeutic potential of LYTENAVA™ as a treatment of wet AMD, ONS-5010/LYTENAVA™’s potential as the first FDA-approved ophthalmic formulation of bevacizumab for use in treating retinal indications, including wet AMD, in the United States, expectations concerning the warrant inducement transaction, including the amount and use of proceeds therefrom, the expected timing of closing, and the stockholder approval required in connection therewith, and other statements that are not historical fact. Although Outlook Therapeutics believes that it has a reasonable basis for the forward-looking statements contained herein, they are based on current expectations about future events affecting Outlook Therapeutics and are subject to risks, uncertainties and factors relating to its operations and business environment, all of which are difficult to predict and many of which are beyond its control. These risk factors include those risks associated with developing and commercializing pharmaceutical product candidates, risks of conducting clinical trials and risks in obtaining necessary regulatory approvals, the content and timing of decisions by regulatory bodies, the sufficiency of Outlook Therapeutics’ resources, as well as those risks detailed in Outlook Therapeutics’ filings with the Securities and Exchange Commission (SEC), including the Annual Report on Form 10-K for the fiscal year ended September 30, 2024, filed with the SEC on December 27, 2024, and future quarterly reports Outlook Therapeutics files with the SEC, which include uncertainty of market conditions and future impacts related to macroeconomic factors, including as a result of the ongoing overseas conflicts, high interest rates, inflation and potential future bank failures on the global business environment. These risks may cause actual results to differ materially from those expressed or implied by forward-looking statements in this press release. All forward-looking statements included in this press release are expressly qualified in their entirety by the foregoing cautionary statements. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Outlook Therapeutics does not undertake any obligation to update, amend or clarify these forward-looking statements whether as a result of new information, future events or otherwise, except as may be required under applicable securities law.
Investor Inquiries:
Jenene Thomas
Chief Executive Officer
JTC Team, LLC
T: 908.824.0775
OTLK@jtcir.com
FAQ
What were the key results of OTLK's NORSE EIGHT trial at 12 weeks?
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