- 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 Part 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 Part 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 international 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 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 permitted focused remedies for folks with pLGG harboring BRAF fusions exterior the U.S.i,iii,iv Day One will keep unique international growth and U.S. business rights for tovorafenib.
David Loew, Chief Govt Officer, Ipsen, commented As we speak’s announcement marks an thrilling addition to our portfolio. Tovorafenib has the potential to make a big affect on kids residing with most cancers and is a superb 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 remedies for folks with pLGG attributable to BRAF alterations, together with BRAF fusions or V600 within the refractory/relapsed setting. We’re delighted to accomplice with the workforce at Day One as we work to convey tovorafenib to each eligible affected person all over the world, who might profit from this necessary new remedy choice.
Jeremy Bender, Ph.D., Chief Govt 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 consider Ipsen’s footprint in Europe and main areas exterior of the U.S., along with their monitor document of bringing revolutionary medicines to market in oncology and uncommon pediatric illnesses, might be an infinite profit to tovorafenib and to the pediatric oncology group worldwide.
Ipsen’s deep heritage and experience in oncology means we will 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 affect their life trajectory.i Relying on the tumor’s dimension, location and development price, pLGG can current with quite a lot of signs together with imaginative and prescient, listening to and speech issues, neurological signs, untimely puberty, bodily adjustments and generalized signs resembling steadiness issues, fatigue and nausea.v Mortality is comparatively uncommon, nonetheless because of the continual nature of pLGG and potential morbidity related to remedy, the illness can considerably have an effect on the event, cognition, schooling and general high quality of lifetime of affected kids, while negatively impacting the psychological well being of fogeys and caregivers.vi,vii
Below the phrases of the settlement, Ipsen might be accountable for the regulatory and business 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 further launch and gross sales milestone funds. Day One will obtain tiered double-digit royalties beginning at mid-teens share 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 almost 100 years of growth expertise and international hubs within the U.S., France and the U.Ok. Our groups in additional than 40 international locations and our partnerships all over the world 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 info, go to ipsen.com.
About Day One Biopharmaceuticals
Day One Biopharmaceuticals believes with regards to pediatric most cancers, we will do higher. Day One was based to deal with a essential 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 attainable for all folks residing with most cancers”no matter age”ranging from Day One.
Day One companions with main medical oncologists, households, and scientists to determine, purchase, and develop necessary focused most cancers remedies. Day One’s pipeline consists of tovorafenib (OJEMDA™), pimasertib and DAY301.
Day One relies in Brisbane, California. For extra info, please go to www.dayonebio.com or comply with Day One on LinkedIn or X.
About tovorafenib
Tovorafenib (often known as OJEMDA™ within the U.S.) is a Sort 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 permitted underneath accelerated approval based mostly, partly, on response price and period 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 (Part III FIREFLY-2/LOGGIC). It’s also 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 evaluate. Tovorafenib has additionally obtained Orphan Drug designation from the FDA for the remedy of malignant glioma and from the European Fee for the remedy of glioma.
For extra info, 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 Part II FIREFLY-1 studyv evaluated the protection and efficacy of tovorafenib in 137 relapsed or refractory BRAF-altered pLGG sufferers, who had obtained at the least one line of prior remedy, throughout two research arms. Arm 1 (n=77) was used for the efficacy analyses and Arm 2 supplied security knowledge for an extra 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 price (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 knowledge cutoff on 5 June 2023 there was a median period 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 pair of), the most typical all-grade treatment-related hostile occasions (TRAEs) have been hair shade adjustments (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 yr who’re eligible for front-line systemic remedy.i,viii BRAF is the gene mostly altered in pLGG, which embrace two major varieties 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 remedies for folks with pLGG pushed by BRAF fusions.i,vi
Pediatric low-grade gliomas could be continual and relentless, with sufferers struggling profound unwanted side effects from each the tumor and the remedy, which can embrace chemotherapy and radiation. These unwanted side effects can affect their life over the long run, and will embrace muscle weak spot, lack of imaginative and prescient, and problem talking. This sort of tumor has a excessive threat 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 might face years of more and more aggressive remedy.
Ipsen contacts
Electronic 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 means 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 supposed to determine 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 taking into consideration external-growth assumptions and potential future acquisitions, which can alter these parameters. These goals are based mostly on knowledge and assumptions considered affordable by Ipsen. These targets rely upon circumstances or details more likely to occur sooner or later, and never completely on historic knowledge. 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 growth section or medical trial might find yourself by no means being launched available on the market or reaching its business 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 growth course of entails a number of levels every of which entails the substantial threat that Ipsen might fail to realize its goals and be compelled to desert its efforts close to a medication through which 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 ample to display the protected 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 might differ materially from these set forth within the forward-looking statements. Different dangers and uncertainties embrace however usually are not restricted to, common business circumstances and competitors; common financial components, together with rate of interest and foreign money alternate price fluctuations; the affect of pharmaceutical business regulation and healthcare laws; international tendencies towards healthcare value containment; technological advances, new medication and patents attained by opponents; challenges inherent in new-medicine growth, together with acquiring regulatory approval; Ipsen’s means to precisely predict future market circumstances; manufacturing difficulties or delays; monetary instability of worldwide economies and sovereign threat; 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 determined by 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 destructive affect 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, except so required by relevant regulation. Ipsen’s enterprise is topic to the chance components outlined in its registration paperwork filed with the French Autorité des Marchés Financiers. The dangers and uncertainties set out usually are not exhaustive and the reader is suggested to consult with Ipsen’s newest Common Registration Doc, accessible on ipsen.com.
Day One Cautionary Observe Concerning Ahead-Wanting Statements
This press launch accommodates forward-looking statements inside the that means of the protected 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 international 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 resembling consider, 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 means to develop, acquire regulatory approval for or commercialize any product candidate, Day One’s means to guard mental property, the potential affect of worldwide enterprise or macroeconomic circumstances, together with because of inflation, rising rates of interest, instability within the international 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 reason why precise outcomes would possibly differ, whether or not because of new info, 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. Obtainable 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.Ok. are based mostly on Ipsen calculations from publicly accessible knowledge (Eurostat, <25yo inhabitants; World Burden of Illness 2019; Desandes et al. Incidence and survival of youngsters with central nervous system primitive tumors within the French Nationwide Registry of Childhood Stable Tumors. Neuro Oncol. 2014 Jul;16(7):975-83. doi: 10.1093/neuonc/not309; Qaddoumi et al. End result 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)
- Ipsen PR_Day One_25072024
