- Ipsen secures ex-U.S. regulatory and business 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 remedy 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 at this time a brand new world partnership outdoors the U.S. for tovorafenib, an oral, once-weekly, kind 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 acquired U.S. FDA approval in April 2024ii as a monotherapy remedy 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 aren’t any accepted focused therapies for individuals with pLGG harboring BRAF fusions outdoors the U.S.i,iii,iv Day One will keep unique world growth and U.S. business 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 influence on kids dwelling with most cancers and is a superb instance of our biomarker-driven technique as we develop our portfolio. Pediatric low-grade glioma is the most typical type of childhood mind most cancers, and, outdoors the U.S., there are nonetheless no accepted focused therapies for individuals with pLGG brought on by BRAF alterations, together with BRAF fusions or V600 within the refractory/relapsed setting. We’re delighted to associate with the staff at Day One as we work to convey tovorafenib to each eligible affected person around the globe, who could profit from this vital new remedy choice.”
Jeremy Bender, Ph.D., Chief Government Officer, Day One commented, “Our collaboration with Ipsen to convey tovorafenib to sufferers worldwide highlights our shared dedication to convey novel therapeutics to sufferers who’ve restricted remedy choices. We imagine Ipsen’s footprint in Europe and main areas outdoors of the U.S., along with their observe report of bringing revolutionary medicines to market in oncology and uncommon pediatric illnesses, will probably be an unlimited profit to tovorafenib and to the pediatric oncology neighborhood worldwide.”
Ipsen’s deep heritage and experience in oncology means we will speed up the supply of this innovation as groups give attention to regulatory actions outdoors the U.S. pLGG is the most typical mind tumor recognized in kids, with sufferers struggling profound tumor- and treatment-associated morbidities that may influence their life trajectory.i Relying on the tumor’s measurement, location and development charge, 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 comparable to steadiness issues, fatigue and nausea.v Mortality is comparatively uncommon, nevertheless because of the continual nature of pLGG and potential morbidity related to remedy, the illness can considerably have an effect on the event, cognition, training and general high quality of lifetime of affected kids, while negatively impacting the psychological well being of fogeys and caregivers.vi,vii
Beneath the phrases of the settlement, Ipsen will probably be answerable for the regulatory and business actions for tovorafenib in all territories outdoors of the U.S. Day One will obtain an upfront fee 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 further 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 give attention to 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 growth expertise and world hubs within the U.S., France and the U.Okay. Our groups in additional than 40 international locations and our partnerships around the globe allow us to convey medicines to sufferers in additional than 80 international locations.
Ipsen is listed in Paris (Euronext: IPN) and within the U.S. by 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 will do higher. Day One was based to deal with a crucial unmet want: the dire lack of therapeutic growth in pediatric most cancers. Impressed by “The Day One Speak” that physicians have with sufferers and their households about an preliminary most cancers prognosis and remedy plan, Day One goals to re-envision most cancers drug growth and redefine what’s potential for all individuals 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 vital 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 known as OJEMDATM 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 remedy 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 accepted underneath accelerated approval based mostly, partly, on response charge and length of response based on 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 remedy (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 strong tumors with MAPK pathway alterations (FIRELIGHT-1).
Tovorafenib was granted Breakthrough Remedy and Uncommon Pediatric Illness designations by the FDA for the remedy of sufferers with pLGG harboring an activating RAF alteration, and it was evaluated by the FDA underneath precedence overview. Tovorafenib has additionally acquired Orphan Drug designation from the FDA for the remedy of malignant glioma and from the European Fee for the remedy 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 performed 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 acquired a minimum of 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 a further 60 sufferers, initiated to allow entry to tovorafenib as soon as Arm 1 had absolutely recruited.ii,iii The first endpoint in Arm 1 of finest general response charge (ORR), decided by unbiased radiology overview 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 based on 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 couple of), the most typical all-grade treatment-related hostile occasions (TRAEs) have been hair shade 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 Further 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 12 months who’re eligible for front-line systemic remedy.i,viii BRAF is the gene mostly altered in pLGG, which embrace two main forms 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 accepted therapies for individuals with pLGG pushed by BRAF fusions.i,vi
Pediatric low-grade gliomas could be continual and relentless, with sufferers struggling profound uncomfortable side effects from each the tumor and the remedy, which can embrace chemotherapy and radiation. These uncomfortable side effects can influence their life over the long run, and should embrace muscle weak spot, lack of imaginative and prescient, and problem talking. One of these tumor has a excessive danger of development, and plenty of kids with pLGG require long-term remedy. Whereas most youngsters with pLGG survive their most cancers, kids who don’t obtain an entire resection following surgical procedure could face years of more and more aggressive remedy.
Ipsen contacts
Electronic mail: company.communications@ipsen.com
Buyers
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
Buyers
PJ Kelleher, LifeSci Advisors pkelleher@lifesciadvisors.com
Media
Laura Cooper, Day One media@dayonebio.com
Disclaimers and/or Ahead-Trying Statements
The forward-looking statements, aims 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 skill to attain its monetary targets, which have been set assuming cheap macroeconomic circumstances based mostly on the knowledge out there at this time. Use of the phrases ‘believes’, ‘anticipates’ and ‘expects’ and related expressions are supposed 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 aims are based mostly on information and assumptions considered cheap by Ipsen. These targets rely on circumstances or info more likely to occur sooner or later, and never completely on historic information. Precise outcomes could depart considerably from these targets given the incidence of sure dangers and uncertainties, notably the truth that a promising drugs in early growth part or medical trial could find yourself by no means being launched in the marketplace or reaching its business targets, notably for regulatory or competitors causes. Ipsen should face or would possibly face competitors from generic drugs which may translate right into a lack of market share. Moreover, the analysis and growth course of includes a number of levels every of which includes the substantial danger that Ipsen could fail to attain its aims and be pressured to desert its efforts as regards to a medication wherein it has invested important sums. Subsequently, Ipsen can’t be sure that favorable outcomes obtained throughout preclinical trials will probably be confirmed subsequently throughout medical trials, or that the outcomes of medical trials will probably be ample to show the secure and efficient nature of the medication involved. There could be no ensures a medication will obtain the required regulatory approvals or that the medication will show to be commercially profitable. If underlying assumptions show inaccurate or dangers or uncertainties materialize, precise outcomes could differ materially from these set forth within the forward-looking statements. Different dangers and uncertainties embrace however aren’t restricted to, normal business circumstances and competitors; normal financial elements, together with rate of interest and forex alternate charge fluctuations; the influence of pharmaceutical business regulation and healthcare laws; world tendencies towards healthcare value containment; technological advances, new drugs and patents attained by opponents; challenges inherent in new-medicine growth, together with acquiring regulatory approval; Ipsen’s skill 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 revolutionary 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 is likely to 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 adverse influence on Ipsen’s enterprise, monetary place or efficiency. Ipsen expressly disclaims any obligation or endeavor 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, until so required by relevant legislation. Ipsen’s enterprise is topic to the chance elements outlined in its registration paperwork filed with the French Autorité des Marchés Financiers. The dangers and uncertainties set out aren’t exhaustive and the reader is suggested to seek advice from Ipsen’s newest Common Registration Doc, out there on ipsen.com.
Day One Cautionary Notice Concerning Ahead-Trying Statements
This press launch comprises “forward-looking” statements throughout the that means of the “secure harbor” provisions of the Non-public 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 power of tovorafenib to deal with pLGG or associated indications.
Statements together with phrases comparable 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 absolutely 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 skill to develop, get hold of regulatory approval for or commercialize any product candidate, Day One’s skill to guard mental property, the potential influence 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 converse 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 legislation.
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/varieties/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 out there information (Eurostat, <25yo inhabitants; World 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. Final result and prognostic options in pediatric gliomas: a overview 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)
