Ipsen and Day One enter into unique ex-U.S. licensing settlement to commercialize tovorafenib for the most typical childhood mind tumor

• Ipsen secures ex-U.S. regulatory and industrial rights to tovorafenib for most typical childhood mind tumor, pediatric low-grade glioma (pLGG), and any future indications
• OJEMDA™ (tovorafenib) is the primary FDA-approved therapy for relapsed or refractory pLGG harboring a BRAF fusion or rearrangement, or V600 mutation, following the pivotal Section II trial, FIREFLY-1
• Day One receives roughly $111 million upfront in money and fairness funding with as much as roughly $350 million in milestone funds and double-digit tiered royalties
• Ongoing Section III trial, FIREFLY-2, is evaluating tovorafenib as a monotherapy for newly recognized kids and younger adults with RAF-altered low-grade glioma requiring first-line systemic remedy

PARIS, FRANCE, and BRISBANE, CALIFORNIA U.S., 25 July 2024 – Ipsen (Euronext: IPN; ADR: IPSEY) and Day One Biopharmaceuticals (Nasdaq: DAWN) (Day One), introduced right now a brand new world partnership exterior the U.S. for tovorafenib, an oral, once-weekly, sort II RAF inhibitor for pediatric low grade glioma (pLGG), the most typical type of childhood mind most cancers, ⁱ and any future indications developed by Day One.

Tovorafenib was granted Orphan Drug Designation and obtained U.S. FDA approval in April 2024ⁱⁱ as a monotherapy therapy for sufferers six months and older with relapsed or refractory pLGG harboring a BRAF fusion or rearrangement, or BRAF V600 mutation.ⁱⁱⁱ These BRAF alterations account for greater than half of pLGG instances worldwide and there are not any permitted focused therapies for folks with pLGG harboring BRAF fusions exterior the U.S.^i,iii,iv Day One will keep unique world improvement and U.S. industrial rights for tovorafenib.

David Loew, Chief Government Officer, Ipsen, commented At the moment’s announcement marks an thrilling addition to our portfolio. Tovorafenib has the potential to make a major impression on kids dwelling with most cancers and is a wonderful instance of our biomarker-driven technique as we broaden our portfolio. Pediatric low-grade glioma is the most typical type of childhood mind most cancers, and, exterior the U.S., there are nonetheless no permitted focused therapies for folks with pLGG brought on by BRAF alterations, together with BRAF fusions or V600 within the refractory/relapsed setting. We’re delighted to companion with the staff at Day One as we work to deliver tovorafenib to each eligible affected person world wide, who might profit from this essential new therapy possibility.

Jeremy Bender, Ph.D., Chief Government Officer, Day One commented, Our collaboration with Ipsen to deliver tovorafenib to sufferers worldwide highlights our shared dedication to deliver novel therapeutics to sufferers who’ve restricted therapy choices. We imagine Ipsen’s footprint in Europe and main areas exterior of the U.S., along with their monitor report of bringing progressive medicines to market in oncology and uncommon pediatric ailments, might be an unlimited profit to tovorafenib and to the pediatric oncology neighborhood worldwide.

Ipsen’s deep heritage and experience in oncology means we are able to speed up the supply of this innovation as groups deal with regulatory actions exterior the U.S. pLGG is the most typical mind tumor recognized in kids, with sufferers struggling profound tumor- and treatment-associated morbidities that may impression their life trajectory.ⁱ Relying on the tumor’s measurement, location and development fee, pLGG can current with a wide range of signs together with imaginative and prescient, listening to and speech issues, neurological signs, untimely puberty, bodily modifications and generalized signs equivalent to steadiness issues, fatigue and nausea.^v Mortality is comparatively uncommon, nevertheless because of the persistent nature of pLGG and potential morbidity related to therapy, the illness can considerably have an effect on the event, cognition, training and total high quality of lifetime of affected kids, while negatively impacting the psychological well being of oldsters and caregivers.^vi,vii

Beneath the phrases of the settlement, Ipsen might be answerable for the regulatory and industrial actions for tovorafenib in all territories exterior of the U.S. Day One will obtain an upfront cost of roughly $111 million, which incorporates roughly $71 million in money in addition to a $40 million fairness funding at a premium and as much as roughly $350 million in extra launch and gross sales milestone funds. Day One will obtain tiered double-digit royalties beginning at mid-teens proportion on gross sales.

ENDS

About Ipsen

We’re a worldwide biopharmaceutical firm with a deal with bringing transformative medicines to sufferers in three therapeutic areas: Oncology, Uncommon Illness and Neuroscience.

Our pipeline is fueled by exterior innovation and supported by practically 100 years of improvement expertise and world hubs within the U.S., France and the U.Okay. Our groups in additional than 40 international locations and our partnerships world wide allow us to deliver medicines to sufferers in additional than 80 international locations.

Ipsen is listed in Paris (Euronext: IPN) and within the U.S. by way of a Sponsored Degree I American Depositary Receipt program (ADR: IPSEY). For extra data, go to ipsen.com.

About Day One Biopharmaceuticals

Day One Biopharmaceuticals believes in terms of pediatric most cancers, we are able to do higher. Day One was based to deal with a essential unmet want: the dire lack of therapeutic improvement in pediatric most cancers. Impressed by The Day One Discuss that physicians have with sufferers and their households about an preliminary most cancers analysis and therapy plan, Day One goals to re-envision most cancers drug improvement and redefine what’s attainable for all folks dwelling with most cancers”no matter age”ranging from Day One.

Day One companions with main medical oncologists, households, and scientists to establish, purchase, and develop essential focused most cancers therapies. Day One’s pipeline consists of tovorafenib (OJEMDA™), pimasertib and DAY301.

Day One relies in Brisbane, California. For extra data, please go to www.dayonebio.com or observe Day One on LinkedIn or X.

About tovorafenib

Tovorafenib (often called OJEMDA^™ within the U.S.) is a Kind II RAF kinase inhibitor mutant BRAF V600, wild-type BRAF, and wild-type CRAF kinases. Tovorafenib is indicated for the therapy of sufferers 6 months of age and older with relapsed or refractory pediatric low-grade glioma (LGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation. This indication is permitted underneath accelerated approval based mostly, partially, on response fee and length of response in line with a number of response evaluation standards: Response Evaluation in Neuro-Oncology Excessive-Grade Glioma (RANO-HGG) standards, Response Evaluation in Pediatric Neuro-Oncology Low-Grade Glioma (RAPNO LGG) standards, and Response Evaluation for Neuro-Oncology Low-Grade Glioma (RANO LGG) standards. Continued approval for this indication could also be contingent upon verification and outline of medical profit in a confirmatory trial(s).

Tovorafenib is underneath analysis as a remedy for sufferers aged 6 months to 25 years with pLGG harboring BRAF fusion or rearrangement, or BRAF V600 mutation requiring front-line therapy (Section III FIREFLY-2/LOGGIC). Additionally it is being studied together with the MEK inhibitor pimasertib for adolescent and grownup affected person populations with recurrent or progressive stable tumors with MAPK pathway alterations (FIRELIGHT-1).

Tovorafenib was granted Breakthrough Remedy and Uncommon Pediatric Illness designations by the FDA for the therapy of sufferers with pLGG harboring an activating RAF alteration, and it was evaluated by the FDA underneath precedence evaluate. Tovorafenib has additionally obtained Orphan Drug designation from the FDA for the therapy of malignant glioma and from the European Fee for the therapy of glioma.

For extra data, please go to www.ojemda.com.

About FIREFLY-1

FIREFLY-1 is evaluating tovorafenib as once-weekly monotherapy in sufferers aged 6 months to 25 years with relapsed or progressive pLGG harboring a recognized activating BRAF alteration. The trial is being carried out in collaboration with the Pacific Pediatric Neuro-Oncology Consortium. The pivotal and ongoing Section II FIREFLY-1 studyv evaluated the security and efficacy of tovorafenib in 137 relapsed or refractory BRAF-altered pLGG sufferers, who had obtained at the very least one line of prior remedy, throughout two examine arms. Arm 1 (n=77) was used for the efficacy analyses and Arm 2 supplied security information for an extra 60 sufferers, initiated to allow entry to tovorafenib as soon as Arm 1 had totally recruited.ii,iii The first endpoint in Arm 1 of finest total response fee (ORR), decided by impartial radiology evaluate committee (IRC) and based mostly on Response Evaluation in Neuro-Oncology Excessive-Grade Glioma (RANO-HGG) standards, achieved ORR of 67% and median time to response (TTR) of three months. On the time of information cutoff on 5 June 2023 there was a median length of response (DOR) of 16.6 months. The secondary endpoint of finest ORR by IRC in line with Response Evaluation in Pediatric Neuro-Oncology Low-Grade Glioma (RAPNO LGG) standards was 51% with a median DOR of 13.8 months and median TTR of 5.3 months. Amongst 137 sufferers (arms 1 and a pair of), the most typical all-grade treatment-related antagonistic occasions (TRAEs) have been hair colour modifications (76%), elevated creatine phosphokinase (56%) and anemia (49%). Grade ‰¥3 TRAEs occurred in 42% of sufferers with elevated creatine phosphokinase (12%) and anemia (10%) as the most typical. 9 (7%) sufferers had TRAEs resulting in discontinuation of tovorafenib.vi Extra details about FIREFLY-1 could also be discovered at ClinicalTrials.gov, utilizing Identifier NCT04775485.

About Pediatric Low-Grade Glioma

Pediatric low-grade glioma (pLGG) is the most typical mind tumor with an estimated US incidence of 1,100 and Europe incidence of 700 kids per yr who’re eligible for front-line systemic remedy.^i,viii BRAF is the gene mostly altered in pLGG, which embody two major kinds of BRAF alterations “ a BRAF gene fusion and BRAF level mutation. These BRAF alterations account for >50% of pLGG instances worldwide and till now there have been no permitted therapies for folks with pLGG pushed by BRAF fusions.^i,vi

Pediatric low-grade gliomas might be persistent and relentless, with sufferers struggling profound unwanted effects from each the tumor and the therapy, which can embody chemotherapy and radiation. These unwanted effects can impression their life over the long run, and should embody muscle weak point, lack of imaginative and prescient, and problem talking. This kind of tumor has a excessive danger of development, and plenty of kids with pLGG require long-term therapy. Whereas most kids with pLGG survive their most cancers, kids who don’t obtain a whole resection following surgical procedure might face years of more and more aggressive therapy.

Ipsen contacts

E-mail:  company.communications@ipsen.com  

Traders

Craig Marks | + 44 7584 349 193

Nicolas Bogler | +33 (0) 6 52 19 98 92

Media

Amy Wolf | +41 7 95 76 07 23

Jess Smith | + 44 7557 267 634

Day One biopharmaceuticals contacts

Traders

PJ Kelleher, LifeSci Advisors pkelleher@lifesciadvisors.com  

Media

Laura Cooper, Day One media@dayonebio.com  

Disclaimers and/or Ahead-Wanting Statements

The forward-looking statements, goals and targets contained herein are based mostly on Ipsen’s administration technique, present views and assumptions. Such statements contain recognized and unknown dangers and uncertainties that will trigger precise outcomes, efficiency or occasions to vary materially from these anticipated herein. The entire above dangers might have an effect on Ipsen’s future capability to realize its monetary targets, which have been set assuming affordable macroeconomic circumstances based mostly on the knowledge accessible right now. Use of the phrases ˜believes’, ˜anticipates’ and ˜expects’ and related expressions are meant to establish forward-looking statements, together with Ipsen’s expectations concerning future occasions, together with regulatory filings and determinations. Furthermore, the targets described on this doc have been ready with out bearing in mind external-growth assumptions and potential future acquisitions, which can alter these parameters. These goals are based mostly on information and assumptions thought to be affordable by Ipsen. These targets rely on circumstances or info prone to occur sooner or later, and never solely on historic information. Precise outcomes might depart considerably from these targets given the incidence of sure dangers and uncertainties, notably the truth that a promising medication in early improvement part or medical trial might find yourself by no means being launched available on the market or reaching its industrial targets, notably for regulatory or competitors causes. Ipsen should face or would possibly face competitors from generic medication which may translate right into a lack of market share. Moreover, the analysis and improvement course of includes a number of levels every of which includes the substantial danger that Ipsen might fail to realize its goals and be compelled to desert its efforts on the subject of a drugs wherein it has invested important sums. Due to this fact, Ipsen can’t be sure that favorable outcomes obtained throughout preclinical trials might be confirmed subsequently throughout medical trials, or that the outcomes of medical trials might be adequate to display the protected and efficient nature of the medication involved. There might be no ensures a drugs will obtain the mandatory regulatory approvals or that the medication will show to be commercially profitable. If underlying assumptions show inaccurate or dangers or uncertainties materialize, precise outcomes might differ materially from these set forth within the forward-looking statements. Different dangers and uncertainties embody however will not be restricted to, normal trade circumstances and competitors; normal financial elements, together with rate of interest and forex trade fee fluctuations; the impression of pharmaceutical trade regulation and healthcare laws; world traits towards healthcare price containment; technological advances, new medication and patents attained by rivals; challenges inherent in new-medicine improvement, together with acquiring regulatory approval; Ipsen’s capability to precisely predict future market circumstances; manufacturing difficulties or delays; monetary instability of worldwide economies and sovereign danger; dependence on the effectiveness of Ipsen’s patents and different protections for progressive medicines; and the publicity to litigation, together with patent litigation, and/or regulatory actions. Ipsen additionally is dependent upon third events to develop and market a few of its medicines which might probably generate substantial royalties; these companions might behave in such methods which might trigger injury to Ipsen’s actions and monetary outcomes. Ipsen can’t be sure that its companions will fulfil their obligations. It could be unable to acquire any profit from these agreements. A default by any of Ipsen’s companions might generate decrease revenues than anticipated. Such conditions might have a unfavorable impression on Ipsen’s enterprise, monetary place or efficiency. Ipsen expressly disclaims any obligation or enterprise to replace or revise any forward-looking statements, targets or estimates contained on this press launch to mirror any change in occasions, circumstances, assumptions or circumstances on which any such statements are based mostly, except so required by relevant regulation. Ipsen’s enterprise is topic to the danger elements outlined in its registration paperwork filed with the French Autorité  des Marchés Financiers. The dangers and uncertainties set out will not be exhaustive and the reader is suggested to check with Ipsen’s newest Common Registration Doc, accessible on  ipsen.com.

Day One Cautionary Be aware Concerning Ahead-Wanting Statements

This press launch accommodates forward-looking statements throughout the that means of the protected harbor provisions of the Personal Securities Litigation Reform Act of 1995, together with, however not restricted to: Day One’s entry into the unique world licensing settlement with Ipsen, Day One’s plans to develop most cancers therapies, expectations from present medical trials, and the flexibility of tovorafenib to deal with pLGG or associated indications.

Statements together with phrases equivalent to imagine, plan, proceed, anticipate, will, develop, sign, potential, or ongoing and statements sooner or later tense are forward-looking statements. These forward-looking statements contain dangers and uncertainties, in addition to assumptions, which, if they don’t totally materialize or show incorrect, might trigger our outcomes to vary materially from these expressed or implied by such forward-looking statements.

Ahead-looking statements are topic to dangers and uncertainties that will trigger Day One’s precise actions or outcomes to vary considerably from these expressed in any forward-looking assertion, together with dangers and uncertainties on this press launch and different dangers set forth in our filings with the Securities and Change Fee, together with Day One’s capability to develop, get hold of regulatory approval for or commercialize any product candidate, Day One’s capability to guard mental property, the potential impression of world enterprise or macroeconomic circumstances, together with on account of inflation, rising rates of interest, instability within the world banking system, geopolitical conflicts and the sufficiency of Day One’s money, money equivalents and investments to fund its operations. These forward-looking statements communicate solely as of the date hereof and Day One particularly disclaims any obligation to replace these forward-looking statements or the explanation why precise outcomes would possibly differ, whether or not on account of new data, future occasions or in any other case, besides as required by regulation.

ⁱ Ryall S, et al. Acta Neuropathol Commun. 2020;8(1):30.
ⁱⁱ FDA grants accelerated approval to tovorafenib for sufferers with relapsed or refractory BRAF-altered pediatric low-grade glioma | FDA (final accessed July 2024)
ⁱⁱⁱ Day One Press Launch. April 2024. Out there right here: Day One’s OJEMDA™ (tovorafenib) Receives US FDA Accelerated Approval for Relapsed or Refractory BRAF-altered Pediatric Low-Grade Glioma (pLGG), the Most Widespread Type of Childhood Mind Tumor | Day One Biopharmaceuticals, Inc. (final accessed July 2024)
^iv Sholl LM. Summary Most cancers Med. 2020;3:26
^vDana-Farber Most cancers Institute. Childhood low-grade gliomas. https://www.dana-farber.org/cancer-care/sorts/childhood-low-grade-gliomas Final accessed: July 2024
^vi Traunwieser T, et al. Neurooncol Adv. 2020;2(1):vdaa094.
^vii Armstrong GT, et al. Neuro Oncol. 2011;13(2):223-234.
^viii Estimates of annual incidence and prevalence for addressable affected person inhabitants in E.U. 4 + U.Okay. are based mostly on Ipsen calculations from publicly accessible information (Eurostat, <25yo inhabitants; International Burden of Illness 2019; Desandes et al. Incidence and survival of kids with central nervous system primitive tumors within the French Nationwide Registry of Childhood Strong Tumors. Neuro Oncol. 2014 Jul;16(7):975-83. doi: 10.1093/neuonc/not309; Qaddoumi et al. Consequence and prognostic options in pediatric gliomas: a evaluate of 6212 instances from the Surveillance, Epidemiology, and Finish Outcomes database. Most cancers. 2009 Dec 15;115(24):5761-70. doi: 10.1002/cncr.24663)

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