A Randomized, Double-Masked, Vehicle-Controlled Parallel Group Clinical Trial to Assess Efficacy and Safety of 0.25% Reproxalap Ophthalmic Solution Compared to Vehicle in Subjects With Dry Eye Disease

Start Date24 Jun 2024

Sponsor / Collaborator

Aldeyra Therapeutics, Inc.

NCT06424444

/ CompletedPhase 3

A Multicenter, Phase 3, Randomized, Double-Masked, Parallel-Group, Vehicle-Controlled, Environment Exposure Clinical Trial to Assess the Efficacy and Safety of 0.25% Reproxalap Ophthalmic Solution Compared to Vehicle in Subjects With Dry Eye Disease

A Multicenter, Phase 3, Randomized, Double-Masked, Parallel-Group, Vehicle-Controlled, Environment Exposure Clinical Trial to Assess the Efficacy and Safety of 0.25% Reproxalap

Start Date29 Apr 2024

Sponsor / Collaborator

Aldeyra Therapeutics, Inc.

NCT06389214

/ CompletedPhase 3

Start Date09 Apr 2024

Sponsor / Collaborator

Aldeyra Therapeutics, Inc.

100 Clinical Results associated with Reproxalap

100 Translational Medicine associated with Reproxalap

100 Patents (Medical) associated with Reproxalap

Literatures (Medical) associated with Reproxalap

01 Aug 2022·Ophthalmology and therapyQ3 · MEDICINE

Reproxalap Activity and Estimation of Clinically Relevant Thresholds for Ocular Itching and Redness in a Randomized Allergic Conjunctivitis Field Trial

Q3 · MEDICINE

ArticleOA

Author: Nichols, Kelly K ; Starr, Christopher E ; Gomes, Paul J ; Brady, Todd C ; Cavanagh, Bill

INTRODUCTION:

This clinical trial assessed the activity of reproxalap, a novel reactive aldehyde species modulator, and estimated clinically relevant thresholds for changes in ocular itching and redness in an allergic conjunctivitis field trial.

METHODS:

This was a randomized, double-masked, vehicle-controlled phase 2 trial. Patients with ragweed-associated allergic conjunctivitis were assessed over 28 days in an environmental setting with approximately four doses per day of either 0.25% reproxalap, 0.5% reproxalap, or vehicle. Patients recorded ocular itching, redness, tearing, and eyelid swelling scores (each with a 0-4 scale, except for a 0-3 scale for swelling), and completed the Allergic Conjunctivitis Quality of Life Questionnaire at the beginning and end of the trial.

RESULTS:

Mixed model of repeated measures analysis demonstrated statistically lower itching and tearing scores (pooled P = 0.026 and P < 0.001, respectively) and numerically lower redness and eyelid swelling scores than vehicle on days when pollen exceeded the 95th percentile value. Using three anchor-based and three distribution-based approaches, the meaningful within-patient change and the between-group meaningful difference for patient-reported ocular itching and redness was estimated to be approximately 0.5. The most common treatment-emergent adverse event associated with reproxalap was transient irritation upon instillation.

CONCLUSION:

In a field clinical trial, reproxalap was well tolerated and superior to vehicle in reducing ocular itching on high-pollen days. The clinical meaningfulness threshold estimates of 0.5 units are among the first such calculations generated for the standard ocular itching and redness scores, providing important context for the clinical interpretation of clinical trials in allergic conjunctivitis.

01 Mar 2022·Molecular genetics and metabolism reportsQ4 · MEDICINE

Sjögren-Larsson syndrome: A biochemical rationale for using aldehyde-reactive therapeutic agents

Q4 · MEDICINE

ArticleOA

Author: S'aulis, Dana ; Rizzo, William B ; Bailey, Zachary ; Dorwart, Elizabeth

Sjögren-Larsson syndrome (SLS) is a neurocutaneous disease caused by mutations in ALDH3A2 that result in deficient fatty aldehyde dehydrogenase (FALDH) activity and impaired fatty aldehyde and fatty alcohol oxidation. The pathogenesis of SLS is thought to involve accumulation of long-chain fatty aldehydes and alcohols and/or metabolically-related ether glycerolipids. Fatty aldehydes are particularly toxic molecules that can covalently react with proteins and certain amino-containing lipids such as phosphatidylethanolamine (PE), generating an unusual aldehyde adduct, N-alkyl-PE (NAPE). Using Faldh-deficient Chinese hamster ovary cells (FAA-K1A) as a cellular model for SLS, we investigated the ability of an aldehyde trapping agent, ADX-102 [2-(3-amino-6-chloro-quinolin-2-yl)-propan-2-ol], to mitigate the harmful effects of fatty aldehydes. FAA-K1A cells were protected from octadecanal (C18:0-al) induced cytotoxicity and apoptosis by ADX-102. Metabolism of C18:0-al to fatty alcohol (octadecanol) was also inhibited by ADX-102. FAA-K1A cells accumulated 5-fold more NAPE with C16- and C18-linked N-alkyl chains compared to wild-type cells, but NAPE levels decreased to normal after growth for 4 days with 50 μM ADX-102. Our results suggest that small aldehyde-reactive molecules, such as ADX-102, should be explored as novel therapeutic agents for SLS by preventing aldehyde adduct formation with critical cellular targets and inhibiting fatty aldehyde metabolism to fatty alcohol.

01 Oct 2021·American journal of ophthalmologyQ2 · MEDICINE

Clinically Relevant Activity of the Novel RASP Inhibitor Reproxalap in Allergic Conjunctivitis: The Phase 3 ALLEVIATE Trial

Q2 · MEDICINE

Article

Author: Karpecki, Paul ; Clark, David ; Cavanagh, Bill ; Shields, Alan L ; Brady, Todd C ; Sheppard, John

PURPOSE:

To assess the post-acute activity and clinical utility of reproxalap, a novel reactive aldehyde species (RASP) inhibitor, versus vehicle in patients with seasonal allergic conjunctivitis.

DESIGN:

Parallel-group, double-masked, randomized Phase 3 trial.

METHODS:

Two topical ocular reproxalap concentrations (0.25% and 0.5%) were evaluated versus vehicle in patients with allergic conjunctivitis randomized 1:1:1 and treated with test article 10 minutes prior to conjunctival seasonal allergen challenge. The primary endpoint was area under the post-acute ocular itching score (range = 0-4) curve from 10 to 60 minutes after challenge. The key secondary endpoint was the proportion of subjects with ≥2 points improvement from their peak ocular itching score at baseline.

RESULTS:

A total of 318 patients were randomized at 11 US sites. Both concentrations of reproxalap (0.25% and 0.5%) achieved the primary endpoint (P < .0001 and P = .003, respectively) and the key secondary endpoint (P = .0005 and P = .02, respectively). Time to complete resolution of ocular itching was statistically faster for both reproxalap concentrations than for vehicle (P < .0001 and P = .001, respectively). No safety or tolerability concerns were noted. The most common adverse event was mild and transient instillation site irritation.

CONCLUSION:

Reproxalap was effective at reducing ocular itching in patients with allergic conjunctivitis. Reproxalap activity was clinically relevant, as assessed by responder-based and distributional analyses. ALLEVIATE represents one of the first allergic conjunctivitis Phase 3 trials of a novel mechanism of action in decades, and is unique among conjunctival allergen challenge trials in assessing clinical relevance with standard and validated techniques.

141

News (Medical) associated with Reproxalap

26 Jun 2025

·www.businesswire.com

Aldeyra Therapeutics Receives Special Protocol Assessment Agreement Letter from the U.S. Food and Drug Administration for ADX-2191 for the Treatment of Primary Vitreoretinal Lymphoma

LEXINGTON, Mass.--(BUSINESS WIRE)--Aldeyra Therapeutics, Inc. (Nasdaq: ALDX) (Aldeyra) today announced receipt of a Special Protocol Assessment Agreement Letter from the U.S. Food and Drug Administration (FDA) for ADX-2191 (methotrexate injection, USP), an investigational drug candidate, for the treatment of primary vitreoretinal lymphoma (PVRL), a rare and potentially fatal cancer currently lacking FDA-approved therapy. “Primary vitreoretinal lymphoma is treated today off label with intravitreal injections of compounded methotrexate,” stated Todd C. Brady, M.D., Ph.D., President and Chief Executive Officer of Aldeyra. “ADX-2191, a novel, vitreous-compatible formulation of methotrexate that is specifically designed for intraocular injection, potentially allows for a reduced injection volume relative to compounding.” Based on a pre-New Drug Application (NDA) meeting with the FDA in December 2022, Aldeyra submitted a literature-based NDA of ADX-2191 for the treatment of PVRL, which was accepted for Priority Review in March 2023. In June 2023, Aldeyra received a Complete Response Letter that stated that the available literature was not sufficient to demonstrate efficacy and that adequate and well-controlled trials were required for approval. The FDA subsequently agreed that a single clinical trial in addition to literature references will be sufficient to support NDA resubmission. The clinical trial proposed in the Special Protocol Assessment will compare cancer cell clearance after 30 days of therapy in up to 20 patients following 1:1 randomization to receive either a single intraocular injection or eight intraocular injections of ADX-2191. The frequency of methotrexate injections has been linked to cancer cell clearance in patients with PVRL,1 and approximately five injections are required on average to achieve cancer cell clearance.2 The clinical trial is expected to begin in the second half of 2025 and conclude in 2026. About ADX-2191 ADX-2191 (methotrexate injection, USP) is a sterile, non-compounded intravitreal formulation of methotrexate for the potential treatment of specific rare retinal diseases, including primary vitreoretinal lymphoma and retinitis pigmentosa. The ADX-2191 intravitreal formulation is preservative-free, is designed to be vitreous-compatible, and is optimized for excipient composition, viscosity, density, tonicity, pH, concentration, and volume of administration. ADX-2191 has received FDA Orphan Drug Designation for the treatment of primary vitreoretinal lymphoma and retinitis pigmentosa. About Primary Vitreoretinal Lymphoma Primary vitreoretinal lymphoma is a rare, aggressive, and potentially fatal retinal cancer that is diagnosed in approximately 300 to 600 patients in the United States per year. The median survival for newly diagnosed patients is less than five years. No approved treatments are currently available, though intravitreal injection of compounded methotrexate represents the current standard of care. About Aldeyra Aldeyra Therapeutics is a biotechnology company devoted to discovering innovative therapies designed to treat immune-mediated and metabolic diseases. Our approach is to develop pharmaceuticals that modulate protein systems, instead of directly inhibiting or activating single protein targets, with the goal of optimizing multiple pathways at once while minimizing toxicity. Our product candidates include RASP (reactive aldehyde species) modulators ADX-629, ADX‑248, ADX-743, ADX-631, ADX-246, and chemically related molecules for the potential treatment of systemic and retinal immune-mediated and metabolic diseases. Our late-stage product candidates are reproxalap, a RASP modulator for the potential treatment of dry eye disease and allergic conjunctivitis, and ADX-2191, a novel formulation of intravitreal methotrexate for the potential treatment of primary vitreoretinal lymphoma and retinitis pigmentosa. Safe Harbor Statement This release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding Aldeyra’s future expectations, plans, and prospects, including without limitation statements regarding: the goals, opportunity, and potential for ADX-2191; the outcome and timing of any clinical trials of ADX-2191; and the outcome and timing of the FDA’s acceptance, review, or approval of a potential NDA resubmission for ADX-2191 and the adequacy of the data expected to be included in such potential resubmitted NDA. Aldeyra intends such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. In some cases, you can identify forward-looking statements by terms such as, but not limited to, “may,” “might,” “will,” “objective,” “intend,” “should,” "could," “can,” “would,” “expect,” “believe,” “anticipate,” “project,” “on track,” “scheduled,” “target,” “design,” “estimate,” “predict,” “contemplates,” “likely,” “potential,” “continue,” “ongoing,” “aim,” “plan,” or the negative of these terms, and similar expressions intended to identify forward-looking statements. Such forward-looking statements are based upon current expectations that involve risks, changes in circumstances, assumptions, and uncertainties. Aldeyra is at an early stage of development and may not ever have any products that generate significant revenue. All of Aldeyra's development timelines may be subject to adjustment depending on recruitment rate, regulatory review, preclinical and clinical results, funding, and other factors that could delay the initiation, enrollment, or completion of clinical trials. Important factors that could cause actual results to differ materially from those reflected in Aldeyra's forward-looking statements include, among others, the timing of enrollment, commencement and completion of Aldeyra's clinical trials, the timing and success of preclinical studies and clinical trials conducted by Aldeyra and its development partners; delay in or failure to obtain regulatory approval of Aldeyra's product candidates, including as a result of the FDA not accepting Aldeyra’s regulatory filings, issuing a complete response letter, or requiring additional clinical trials or data prior to review or approval of such filings or in connection with resubmissions of such filings; the ability to maintain regulatory approval of Aldeyra's product candidates, and the labeling for any approved products; the risk that prior results, such as signals of safety, activity, or durability of effect, observed from preclinical or clinical trials, will not be replicated or will not continue in ongoing or future studies or clinical trials involving Aldeyra's product candidates in clinical trials focused on the same or different indications; the scope, progress, expansion, and costs of developing and commercializing Aldeyra's product candidates; uncertainty as to Aldeyra’s ability to commercialize (alone or with others) and obtain reimbursement for Aldeyra's product candidates following regulatory approval, if any; the size and growth of the potential markets and pricing for Aldeyra's product candidates and the ability to serve those markets; Aldeyra's expectations regarding Aldeyra's expenses and future revenue, the timing of future revenue, the sufficiency or use of Aldeyra's cash resources and needs for additional financing; the rate and degree of market acceptance of any of Aldeyra's product candidates; Aldeyra's expectations regarding competition; Aldeyra's anticipated growth strategies; Aldeyra's ability to attract or retain key personnel; Aldeyra’s commercialization, marketing and manufacturing capabilities and strategy; Aldeyra's ability to establish and maintain development partnerships; Aldeyra’s ability to successfully integrate acquisitions into its business; Aldeyra's expectations regarding federal, state, and foreign regulatory requirements; political, economic, legal, social, and health risks, public health measures, and war or other military actions, that may affect Aldeyra’s business or the global economy; regulatory developments in the United States and foreign countries; Aldeyra's ability to obtain and maintain intellectual property protection for its product candidates; the anticipated trends and challenges in Aldeyra's business and the market in which it operates; and other factors that are described in the “Risk Factors” and “Management's Discussion and Analysis of Financial Condition and Results of Operations” sections of Aldeyra's Annual Report on Form 10-K for the year ended December 31, 2024, and Aldeyra’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2025, which are on file with the Securities and Exchange Commission (SEC) and available on the SEC website at https://www.sec.gov/. Additional factors may be described in those sections of Aldeyra’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2025, expected to be filed with the SEC in the third quarter of 2025, and Aldeyra’s other filings with the SEC. In addition to the risks described above and in Aldeyra's other filings with the SEC, other unknown or unpredictable factors also could affect Aldeyra's results. No forward-looking statements can be guaranteed and actual results may differ materially from such statements. The information in this release is provided only as of the date of this release, and Aldeyra undertakes no obligation to update any forward-looking statements contained in this release on account of new information, future events, or otherwise, except as required by law. 1 Am J Ophthalmol 251: 189–196, 2023 2 Br J Haematol, 194, 92–100, 2021; Cancer Sci. 107:1458-1464, 2016

NDAPriority ReviewOrphan Drug

17 Jun 2025

·www.businesswire.com

Aldeyra Therapeutics Resubmits Reproxalap New Drug Application for the Treatment of Dry Eye Disease

LEXINGTON, Mass.--(BUSINESS WIRE)--Aldeyra Therapeutics, Inc. (Nasdaq: ALDX) (Aldeyra), a biotechnology company devoted to discovering and developing innovative therapies designed to treat immune‑mediated and metabolic diseases, today announced the resubmission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for topical ocular reproxalap, an investigational new drug candidate, for the treatment of signs and symptoms of dry eye disease. Per FDA agreement, the only new clinical data included in the resubmitted NDA were from the recently completed dry eye chamber trial, which achieved the primary endpoint. “Consistent with a number of clinical trials that suggest the potential of reproxalap to rapidly improve the symptoms of dry eye disease, we believe the clinical trial results included in the resubmission announced today are robust,” stated Todd C. Brady, M.D., Ph.D., President and Chief Executive Officer of Aldeyra. “Based on the lack of notable baseline differences across treatment arms and the highly statistically significant achievement of the prespecified primary endpoint in favor of reproxalap over vehicle, in conjunction with recent FDA discussions, we believe that previous concerns raised by the FDA have been addressed.” In April 2025, Aldeyra received a Complete Response Letter from the FDA that stated that potential methodological issues in a previously completed dry eye chamber trial, including a baseline difference across treatment arms, may have affected the interpretation of the results; the letter stated that an additional symptom trial would be required for resubmission. In May 2025, Aldeyra announced the achievement of the primary endpoint (P=0.002) in a Phase 3 randomized, double‑masked, vehicle‑controlled dry eye chamber trial that assessed the activity of reproxalap in reducing ocular discomfort, an FDA‑accepted symptom of dry eye disease. No notable differences in baseline scores across treatment arms were observed in the clinical trial, and no safety concerns were identified. Consistent with prior clinical trials, the most common adverse event was mild and transient instillation site discomfort, which most commonly lasted less than one minute. The Prescription Drug User Fee Act target guidelines for NDA resubmissions include acknowledgment of acceptance for review within 30 days of submission, and completion of submission review within 6 months. About Reproxalap Reproxalap is an investigational new drug candidate in development for the treatment of dry eye disease and allergic conjunctivitis, two of the largest markets in ophthalmology. Reproxalap is a first‑in‑class small‑molecule modulator of RASP, which are elevated in ocular and systemic inflammatory diseases. The mechanism of action of reproxalap has been supported by the demonstration of statistically significant and clinically relevant activity in multiple physiologically distinct late‑phase clinical indications. Reproxalap has been studied in more than 2,900 patients with no observed safety concerns; mild and transient instillation site irritation is the most commonly reported adverse event in clinical trials. About Aldeyra Aldeyra Therapeutics is a biotechnology company devoted to discovering innovative therapies designed to treat immune‑mediated and metabolic diseases. Our approach is to develop pharmaceuticals that modulate protein systems, instead of directly inhibiting or activating single protein targets, with the goal of optimizing multiple pathways at once while minimizing toxicity. Our product candidates include RASP (reactive aldehyde species) modulators ADX‑629, ADX‑248, ADX‑743, ADX‑631, ADX‑246, and chemically related molecules for the potential treatment of systemic and retinal immune‑mediated and metabolic diseases. Our late‑stage product candidates are reproxalap, a RASP modulator for the potential treatment of dry eye disease and allergic conjunctivitis, and ADX‑2191, a novel formulation of intravitreal methotrexate for the potential treatment of retinitis pigmentosa. Safe Harbor Statement This release contains forward‑looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding Aldeyra’s future expectations, plans, and prospects, including without limitation statements regarding: the goals, opportunity, and potential for reproxalap; and the outcome and timing of the FDA’s acceptance, review, or approval of the NDA resubmission for reproxalap and the adequacy of the data included in the initial NDA and resubmitted NDAs. Aldeyra intends such forward‑looking statements to be covered by the safe harbor provisions for forward‑looking statements contained in Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. In some cases, you can identify forward‑looking statements by terms such as, but not limited to, “may,” “might,” “will,” “objective,” “intend,” “should,” "could," “can,” “would,” “expect,” “believe,” “anticipate,” “project,” “on track,” “scheduled,” “target,” “design,” “estimate,” “predict,” “contemplates,” “likely,” “potential,” “continue,” “ongoing,” “aim,” “plan,” or the negative of these terms, and similar expressions intended to identify forward‑looking statements. Such forward‑looking statements are based upon current expectations that involve risks, changes in circumstances, assumptions, and uncertainties. Aldeyra is at an early stage of development and may not ever have any products that generate significant revenue. All of Aldeyra's development timelines may be subject to adjustment depending on recruitment rate, regulatory review, preclinical and clinical results, funding, and other factors that could delay the initiation, enrollment, or completion of clinical trials. Important factors that could cause actual results to differ materially from those reflected in Aldeyra's forward‑looking statements include, among others, the timing of enrollment, commencement and completion of Aldeyra's clinical trials, the timing and success of preclinical studies and clinical trials conducted by Aldeyra and its development partners; delay in or failure to obtain regulatory approval of Aldeyra's product candidates, including as a result of the FDA not accepting Aldeyra’s regulatory filings, issuing a complete response letter, or requiring additional clinical trials or data prior to review or approval of such filings or in connection with resubmissions of such filings; the ability to maintain regulatory approval of Aldeyra's product candidates, and the labeling for any approved products; the risk that prior results, such as signals of safety, activity, or durability of effect, observed from preclinical or clinical trials, will not be replicated or will not continue in ongoing or future studies or clinical trials involving Aldeyra's product candidates in clinical trials focused on the same or different indications; the scope, progress, expansion, and costs of developing and commercializing Aldeyra's product candidates; uncertainty as to Aldeyra’s ability to commercialize (alone or with others) and obtain reimbursement for Aldeyra's product candidates following regulatory approval, if any; the size and growth of the potential markets and pricing for Aldeyra's product candidates and the ability to serve those markets; Aldeyra's expectations regarding Aldeyra's expenses and future revenue, the timing of future revenue, the sufficiency or use of Aldeyra's cash resources and needs for additional financing; the rate and degree of market acceptance of any of Aldeyra's product candidates; Aldeyra's expectations regarding competition; Aldeyra's anticipated growth strategies; Aldeyra's ability to attract or retain key personnel; Aldeyra’s commercialization, marketing and manufacturing capabilities and strategy; Aldeyra's ability to establish and maintain development partnerships; Aldeyra’s ability to successfully integrate acquisitions into its business; Aldeyra's expectations regarding federal, state, and foreign regulatory requirements; political, economic, legal, social, and health risks, public health measures, and war or other military actions, that may affect Aldeyra’s business or the global economy; regulatory developments in the United States and foreign countries; Aldeyra's ability to obtain and maintain intellectual property protection for its product candidates; the anticipated trends and challenges in Aldeyra's business and the market in which it operates; and other factors that are described in the “Risk Factors” and “Management's Discussion and Analysis of Financial Condition and Results of Operations” sections of Aldeyra's Annual Report on Form 10‑K for the year ended December 31, 2024, and Aldeyra’s Quarterly Report on Form 10‑Q for the quarter ended March 31, 2025, which are on file with the Securities and Exchange Commission (SEC) and available on the SEC's website at https://www.sec.gov/. Additional factors may be described in those sections of Aldeyra’s Quarterly Report on Form 10‑Q for the quarter ended June 30, 2025, expected to be filed with the SEC in the third quarter of 2025, and Aldeyra’s other filings with the SEC. In addition to the risks described above and in Aldeyra's other filings with the SEC, other unknown or unpredictable factors also could affect Aldeyra's results. No forward‑looking statements can be guaranteed and actual results may differ materially from such statements. The information in this release is provided only as of the date of this release, and Aldeyra undertakes no obligation to update any forward‑looking statements contained in this release on account of new information, future events, or otherwise, except as required by law.

Phase 3NDAClinical Result

11 Jun 2025

·www.biospace.com

Biopharma Right of First Negotiation Not a Golden Ticket to M&A, Jefferies Finds

iStock, Anastasiia_New Looking at licensing deals struck in the past 10 years, Jefferies found that many Big Pharmas do not ultimately follow through with M&A after earning a right of first negotiation. Sanofi, on the other hand, almost always does, as it did with Vigil recently. For biotech, a right of first negotiation to a buyout is not always a ticket to M&A, a new report from Jefferies suggests. But Sanofi’s $470 million acquisition of Vigil Neuroscience—which indeed stemmed from such a clause in a previous licensing deal—has reinvigorated interest in the idea of ROFNs. Jefferies took a look at 50 ROFN agreements that have occurred across biopharma in the past 10 or so years. These agreements are sometimes included in licensing agreements between two companies with varying terms such as providing a first shot at deal talks if the smaller company decides to sell. They can also pertain to single assets or for future drug development or commercialization opt-ins. Many Big Pharmas do not ultimately follow through despite including a ROFN in a licensing deal, Jefferies found. But somehave led to business development collaborations instead, such as AbbVie’s partnership with Aldeyra Therapeutics and GSK’s pact with Liquidia Corporation. Sanofi is a particularly big fan of including ROFNs in its licensing deals. Vigil is the most recent example, but Jefferies flagged three more outstanding from the pharma: with Ventyx Biosciences, Zucara and MeiraGTx. In the case of Vigil, Sanofi provided $40 million in capital back in July 2024, securing the ROFN for Alzheimer’s disease asset VG-3927. Eleven months later, Sanofi apparently saw all it needed to and executed on an acquisition of the entire company, save for one asset that was to be returned to Amgen . Other companies with ROFNs still on the books include Pfizer and Axsome Therapeutics, Gilead and Nektar Therapeutics, and Catalyst Pharmaceuticals and Santhera Pharmaceuticals. Below, BioSpace looks at five ROFN agreements across biopharma that are still chugging along—or not. Ventyx Rises as Sanofi Buys Out Peer Of Sanofi’s multiple deals including a ROFN is its $27 million investment in Ventyx Biosciences. Struck last year, the contract gave Sanofi an exclusive right to have the first say in the prospects of VTX3232, a central nervous system-penetrant NLRP3 inhibitor in Phase II development. Ventyx is expecting multiple major readouts for VTX3232 this year, including in Parkinson’s disease and in subjects with obesity and additional cardiometabolic risk factors. Ventyx’s shares climbed when Sanofi acquired Vigil, given the similar focus on CNS diseases. Through the ROFN, Sanofi has gained the right to an exclusive period of time to negotiate a potential deal, but the clause does not stop another pharma from putting in an offer. Jefferies suggested that Eli Lilly or AbbVie could be interested , as Ventyx’s work crosses between immunology and CNS. The cardiometabolic data could also be a nice boost to Ventyx’s fortunes; Jefferies referred to this as a “wild card” that could be an add on for for GLP-1 therapies. AbbVie Gets First Eye on Aldeyra’s Ophthalmology Work AbbVie zeroed in on Aldeyra’s dry eye disease therapy reproxalap in November 2023, inking a deal worth up to $400 million. AbbVie snagged a 60%-40% profit split with Aldeyra for sales in the U.S., while the latter would receive royalties on ex-U.S. sales. Since then, the regulatory process for reproxalap has not gone smoothly . Aldeyra has received two FDA rejections of the drug’s application for dry eye disease. Most recently, the FDA issued a complete response letter in April stating that reproxalap “failed to demonstrate efficacy in adequate and well-controlled studies in treating ocular symptoms associated with dry eyes.” The agency asked for another trial with a positive effect on the ocular symptoms of dry eye. AbbVie has an option agreement on reproxalap that requires a decision 10 days after an FDA approval is achieved, if any, meaning it remains open. The original AbbVie-Aldeyra deal also included a ROFN for AbbVie on “compounds that are owned or otherwise controlled by Aldeyra” in ophthalmology, particularly therapies for treating conditions of the ocular surface. AbbVie also negotiated the right to review data for any of these compounds in ophthalmology as well as immunology before anyone else gets a look. Aldeyra’s other pipeline meds include the retinitis pigmentosa injection ADX-2191 and ADX-248 for atopic dermatitis, which is in Phase I. AstraZeneca and Conduit’s Convoluted Deal Licensing deals typically involve a bigger company taking on a smaller biotech’s assets for development, but this deal gets strange as you dig deeper. Conduit Pharma and AstraZeneca partnered in August 2024, with the U.K.-pharma providing Conduit with exclusive licensing rights to the HK-4 glucokinase activators AZD1656 and AZD5658, as well as the myeloperoxidase inhibitor AZD5904. Conduit’s structure is unique. The company acquires and funds development of Phase II-ready assets, then fuels them toward Phase II before selling the rights to a third party if all goes well. AZD1656, AZD5658 and AZD5904 are originally AstraZeneca’s drugs—so a ROFN clause fits in nicely as AstraZeneca clearly didn’t want to let them go fully as Conduit tested some of them in new indications. AZD1656, which is being tested in lupus, was originally developed by AstraZeneca for diabetes, meaning Coinduit is essentially handling the mid-phase lifecycle of the drug’s development in the new indication. The drug had already been tested in thousands of patients and more than a dozen trials before Conduit began its work, so the safety record was firmly established by AstraZeneca allowing for quick advancement. Conduit developed a new formulation to improve on the physicochemical properties of the drug and is currently working on Phase II trials. Besides the ROFN, AstraZeneca took ownership of common stock in Conduit as part of the deal, though the details were not disclosed. As of March, Conduit was working on initiating the Phase II trials with results expected in the second half of this year. AZD1656 is also being tested for ANCA vasculitis, while AZD5658 is earmarked for autoimmune disorders and AZD5904 is in trials for idiopathic male infertility. Lilly Dealt With Innovent in China Before It Was Cool Partnerships with Chinese biotechs have been all the rage lately , but Eli Lilly saw the light at least a decade ago when it signed a partnership with Innovent Biologics. The deal initially focused on three therapies , one of which would become the approved PD-1 inhibitor Tyvyt. Innovent received $56 million upfront plus up to $400 million in milestones. Over the years, the deal has been revamped and renegotiated, with Innovent nabbing in-China rights to some of Lilly’s medicines. In 2022, the Chinese biotech took on the rights to Cyramza and Retsevmo, and earned a ROFN on future commercialization of the Bruton’s tyrosine kinase (BTK) inhibitor Jaypirca in China. The ROFN was achieved in December 2024, with Innovent officially achieving commercialization of Jaypirca in mainland China. Biogen Scales Back Denali Work This one has been rocky. Biogen and Denali Therapeutics originally tied up in August 2020, agreeing to work on neurodegenerative diseases including Parkinson’s. Denali received $560 million upfront, plus $465 million in equity from Biogen and the possibility of milestones down the line. The original focus was on Denali’s small molecule LRRK2 inhibitor program, but Biogen also received an exclusive option on two programs that utilized the biotech’s platform technology for crossing the blood-brain barrier (BBB). These two programs included a ROFN. Biogen exercised its rights to one of the two neurodegenerative programs in April 2023 for Alzheimer’s disease. On one part of the Parkinson’s program, however, progress turned out to be too slow for Biogen, which cut a trial for BIIB122 that wasn’t expected to read out until 2031, according to a June 2023 release . Then in August 2024, Biogen ended the Alzheimer’s work too, leaving Denali to pick up the pieces. The partners continue to advance the LRRK2, called BIIB122/DNL151, in a Phase IIb trial. The BBB-crossing tech program is still in investigational new drug application pre-clinical testing. The Biogen trouble has been just one aspect of Denali’s rocky few years. The company’s Sanofi-partnered multiple sclerosis program was canned in October 2024 after failing a Phase II trial. The same drug also failed a test in amyotrophic lateral sclerosis (ALS) earlier the same year. And in January, Denali suffered another ALS failure as part of the HEALEY ALS platform study .

Phase 2License out/inPhase 1Acquisition

100 Deals associated with Reproxalap

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Xerophthalmia	NDA/BLA	United States	Aldeyra Therapeutics, Inc.	04 Oct 2024
Dry Eye Syndromes	Phase 3	Canada	Aldeyra Therapeutics, Inc.	09 Apr 2024
Seasonal allergic conjunctivitis	Phase 3	Canada	Aldeyra Therapeutics, Inc.	05 Dec 2019
Sjogren-Larsson Syndrome	Phase 3	United States	Aldeyra Therapeutics, Inc.	18 Jul 2018
Acute conjunctivitis	Phase 3	United States	Aldeyra Therapeutics, Inc.	30 Mar 2018
Conjunctivitis, Allergic	Phase 3	United States	Aldeyra Therapeutics, Inc.	30 Mar 2018
Non-infectious anterior uveitis	Phase 3	United States	Aldeyra Therapeutics, Inc.	26 Apr 2017
Rhinitis, Allergic, Seasonal	Phase 2	Canada	Aldeyra Therapeutics, Inc.	01 Aug 2015

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT06493604 (BusinessWire) Manual	Phase 3	Dry Eye Syndromes	116	Reproxalap	vdihcbkrws(fhnljobqsp): Difference (LS Mean) = ‑6.5 (95% CI, ‑10.5 - ‑2.5), P-Value = 0.002 Met	Positive	05 May 2025
				vehicle
NCT03660878 (CTgov)	Phase 1/2	Seasonal allergic conjunctivitis	52	Reproxalap Ophthalmic Solution (0.25%) (Reproxalap Ophthalmic Solution (0.25%))	vxjbsyzsrl(lrtwvwrbnd) = lrhudyklef bzczmmscif (ycclrkhxkh, 0.17) View more	-	08 Apr 2025
				Vehicle Ophthalmic Solution (Vehicle Ophthalmic Solution)	vxjbsyzsrl(lrtwvwrbnd) = qdcodxkoza bzczmmscif (ycclrkhxkh, 0.18) View more
NCT05102409 (CTgov)	Phase 2	Dry Eye Syndromes	56	Reproxalap (Reproxalap)	msbtokbdrs(bovosnnqqt) = jjnhxdcvmf ofuwqhhkmm (mefucrttxl, 0.21) View more	-	28 Feb 2025
				Lifitegrast (Lifitegrast)	msbtokbdrs(bovosnnqqt) = toogwyjrdy ofuwqhhkmm (mefucrttxl, 0.25) View more
NCT03494504 (CTgov)	Phase 3	Acute conjunctivitis \| Conjunctivitis, Allergic	318	Reproxalap Ophthalmic Solution (0.25%) (Reproxalap Ophthalmic Solution (0.25%))	ufonnwveka(mhpieiccgo) = alxzopgwbj jzecwypmjg (fwewhxpjqq, 3.3053) View more	-	11 Feb 2025
				Reproxalap Ophthalmic Solution (0.5%) (Reproxalap Ophthalmic Solution (0.5%))	ufonnwveka(mhpieiccgo) = cjdaemawqc jzecwypmjg (fwewhxpjqq, 3.4552) View more
NCT03879863 (RENEW, CTgov)	Phase 3	Dry Eye Syndromes	422	Reproxalap (Reproxalap Ophthalmic Solution (0.25%) QID)	bfmutwwauv(scowypflow) = bxdwroyzwl fddclzehgu (oqiuwfpenm, 2.44) View more	-	23 Jan 2025
				Vehicle Ophthalmic Solution QID (Vehicle Ophthalmic Solution QID)	bfmutwwauv(scowypflow) = imamjyunny fddclzehgu (oqiuwfpenm, 2.39) View more
NCT03162783 (CTgov)	Phase 2	Dry Eye Syndromes	51	ADX-102 Ophthalmic Solution (0.1%) (ADX-102 Ophthalmic Solution (0.1%))	bqicrxvezd(trpjirwnos) = aqlnwmitwe uvkbnaixeh (xssbdyovuq, 0.98) View more	-	16 Jan 2025
				ADX-102 Ophthalmic Solution (0.5%) (ADX-102 Ophthalmic Solution (0.5%))	bqicrxvezd(trpjirwnos) = mubezrvjwu uvkbnaixeh (xssbdyovuq, 0.75) View more
NCT06389214 (BusinessWire) Manual	Phase 3	Dry Eye Syndromes	132	0.25% reproxalap	gamopspovq(uzikfayqao): P-Value = 0.004 Met View more	Positive	08 Aug 2024
				vehicle
NCT05234554 (Phase III Clinical Trial, AAAAI2024)	Phase 3	Seasonal allergic conjunctivitis	-	Reproxalap Ophthalmic Solution (0.25%)	qwprorclog(nqwecqqfzv) = otmhjfwatt kwytthyxzq (gznucgcxgq ) View more	Positive	23 Feb 2024
				Vehicle	qwprorclog(nqwecqqfzv) = rooallbfbl kwytthyxzq (gznucgcxgq ) View more
NCT05234554 (INVIGORATE-2, Corporate Publications) Manual	Phase 3	Seasonal allergic conjunctivitis	131	Reproxalap	gjxidoziuq(bwisvdsqdy): P-Value = <0.0001 Met View more	Positive	15 Jun 2023
				Placebo
NCT03445650 (CTgov)	Phase 3	Sjogren-Larsson Syndrome	11	ADX-102 (ADX-102 1% Topical Dermal Cream)	sqiccqcavb(ypfjesojof) = jveodntfcg xywgfznmzm (cdijilhrbe, 0.22) View more	-	09 Feb 2023
				ADX-102 (Vehicle Topical Dermal Cream)	fgavstgxwv(rkisfjxxkg) = houkdmqxct qwcgqvxjxb (bvgesasxyv, bvbeimpocv - dodolchunl) View more

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