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.
