SpringWorks Therapeutics Announces Presentation of Additional Data from Phase 3 DeFi Trial of Nirogacestat in Adults with Desmoid Tumors at the 2023 ASCO Annual Meeting

– Nirogacestat Therapy Demonstrated Fast, Sustained and Constant Reductions in Ache In comparison with Placebo Utilizing A number of Evaluation Instruments –

– Substantial Reductions in MRI-Assessed Tumor Quantity and T2 Hyperintensity Noticed with Nirogacestat In comparison with Placebo –

STAMFORD, Conn., Might 25, 2023 (GLOBE NEWSWIRE) — SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a clinical-stage biopharmaceutical firm targeted on creating life-changing medicines for sufferers with extreme uncommon illnesses and most cancers, at the moment introduced that further knowledge from the Part 3 DeFi trial assessing the impression of nirogacestat, an investigational gamma secretase inhibitor, on ache, tumor quantity and T2 hypersensitivity in adults with desmoid tumors shall be introduced on the 2023 American Society of Medical Oncology (ASCO) Annual Assembly, being held June 2-6, 2023. Knowledge from the DeFi trial have been beforehand introduced on the European Society for Medical Oncology Congress in September 2022 and revealed within the March 9, 2023 version of the New England Journal of Medication.¹

“Ache is essentially the most debilitating symptom reported by sufferers dwelling with desmoid tumors and decreasing this burden is a key therapy purpose for physicians. We’re happy with the sturdy knowledge noticed utilizing a number of evaluation instruments demonstrating clinically vital reductions in ache with nirogacestat therapy,” stated Jim Cassidy, M.D., Ph.D., Chief Medical Officer of SpringWorks. “We’re additionally inspired by the substantial reductions in tumor quantity and T2 hyperintensity seen within the DeFi research, that are according to the numerous enhancements in progression-free survival and goal response charge beforehand reported, and additional elaborate on the exercise profile of nirogacestat in desmoid tumors. We consider that nirogacestat has the potential to be a major advance for sufferers and we sit up for our continued discussions with the FDA as they evaluation our New Drug Utility.”

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Poster Displays on the 2023 ASCO Annual Assembly

Impression of nirogacestat on ache, a key symptom in sufferers with desmoid tumors (DT): outcomes from the Part 3 DeFi research (Poster #: 498)

Summary #: 11564

Poster Session Date and Time: Saturday, June 3, 1:15 – 4:15 p.m. CT (2:15 – 5:15 p.m. ET)

As beforehand reported, within the DeFi trial (NCT03785964), nirogacestat met its main endpoint of considerably enhancing progression-free survival in comparison with placebo in grownup sufferers with progressing desmoid tumors (hazard ratio: 0.29 [95% CI, 0.15–0.55]; P<0.001). Nirogacestat additionally achieved a major and clinically significant discount in ache severity, a key secondary endpoint, in contrast with placebo at Cycle 10 (P<0.001). A manageable security profile was noticed with nirogacestat, with 95% of all treatment-emergent adversarial occasions (TEAEs) reported as both Grade 1 or 2. Probably the most continuously reported TEAEs that occurred in contributors receiving nirogacestat have been diarrhea (84%), nausea (54%), fatigue (51%), hypophosphatemia (42%), and maculopapular rash (32%).

In the course of the DeFi research, sufferers additionally accomplished three prespecified evaluation instruments that included ache measurements to characterize the impression of nirogacestat on this symptom. Adjustments from baseline in ache severity have been in contrast between therapy arms at Cycle 10 per the prespecified exploratory endpoints. Statistically vital and clinically significant reductions in ache have been noticed with nirogacestat in contrast with placebo at Cycle 10 throughout all three evaluation instruments evaluated in DeFi: the Temporary Ache Stock-Brief Kind (BPI-SF), the GOunder/Desmoid Tumor Analysis Basis DEsmoid Symptom Scale (GODDESS-DTSS), and the European Organisation for Analysis and Therapy of Most cancers Core High quality of Life Questionnaire (EORTC QLQ-C30).

The next outcomes from the evaluation instruments shall be introduced at ASCO:

• Nirogacestat considerably lowered ache severity per the BPI-SF “worst ache” rating (0–10 vary) by 1.55 factors, in contrast with 0.05 factors with placebo (P<0.001) at Cycle 10.

• Nirogacestat considerably lowered ache per the GODDESS-DTSS ache rating (0–10 vary) by 1.78 factors, in contrast with a rise in ache of 0.34 factors with placebo (P<0.001) at Cycle 10. The GODDESS-DTSS ache rating consists of questions on worst ache, uninteresting ache, and capturing ache.

• Nirogacestat considerably lowered ache per the EORTC QLQ-C30 ache subscale (0–100 vary) by 22.36 factors, in contrast with a rise in ache of seven.00 factors with placebo (P<0.001) at Cycle 10. This ache sub-scale consists of questions on ache and its interference with each day actions.

• A statistically vital better proportion of sufferers achieved a clinically significant ache discount with nirogacestat therapy in contrast with placebo at Cycle 10 per the BPI-SF “worst ache” rating (P=0.001) and the GODDESS-DTSS ache rating (P<0.001).

• Reductions in ache have been fast, turning into evident as early as Cycle 2 (the primary post-treatment timepoint evaluated), and these reductions have been sustained by way of to the tip of the double-blind part of the DeFi trial.

“Many sufferers with desmoid tumors dwell with extreme, power ache that considerably impacts their high quality of life,” stated Winette T.A. van der Graaf, M.D., Ph.D., Group Chief and Medical Oncologist, Division of Medical Oncology, Netherlands Most cancers Institute, Amsterdam, Netherlands and investigator within the DeFi trial. “It is extremely encouraging that nirogacestat demonstrated a fast, sustained and constant discount in several features of ache throughout the trial, together with worst ache, uninteresting ache, capturing ache, and ache interference with individuals’s skill to carry out each day actions.”

Tumor quantity and T2 hyperintensity modifications from DeFi: a Part 3, randomized, managed trial of nirogacestat in sufferers with desmoid tumors (Poster #: 448)

Summary #: 11514

Poster Session Date and Time: Saturday, June 3, 4:30 – 6:00 p.m. CT (5:30 – 7:00 p.m. ET); Poster Dialogue at 4:30 p.m. CT (5:30 p.m. ET).

Exploratory analyses have been performed to guage modifications in MRI-assessed desmoid tumor quantity and T2 sign depth within the Part 3 DeFi trial. Particularly, volumetric MRI and T2 hyperintensity of every affected person’s largest goal tumor have been evaluated at screening and each 6 cycles thereafter throughout the double-blind part of the research. Using MRI to evaluate modifications in tumor quantity or T2 sign depth characterize a novel imaging method that would have prognostic or predictive worth in sufferers with desmoid tumors.

Therapy with nirogacestat led to considerably improved median greatest change from baseline in MRI-assessed tumor quantity of the most important goal tumor in contrast with placebo (–59% versus +14%; P<0.001). Therapy with nirogacestat additionally led to vital enchancment within the median greatest % change in T2 hyperintensity sign ratio of the most important goal tumor in contrast with placebo (–55% versus –21%; P<0.001).

“The Part 3 DeFi research is the most important trial to this point to prospectively consider volumetric MRI and T2 hyperintensity leads to sufferers with desmoid tumors,” stated Thierry Alcindor, M.D., MSc, Medical Oncologist, Dana-Farber Most cancers Institute and investigator within the DeFi trial. “These outcomes are according to the numerous enhancements in progression-free survival and goal response charge achieved with nirogacestat in comparison with placebo in DeFi and characterize another method to imaging sufferers with desmoid tumors that will higher seize the uneven and irregular progress of those tumors.”

Concerning the DeFi Trial

DeFi (NCT03785964) is a worldwide, randomized (1:1), double-blind, placebo-controlled Part 3 trial evaluating the efficacy, security and tolerability of nirogacestat in grownup sufferers with progressing desmoid tumors. The double-blind part of the research randomized 142 sufferers (nirogacestat, n=70; placebo n=72) to obtain 150 mg of nirogacestat or placebo twice each day. Key eligibility standards included tumor development by ≥20% as measured by Response Analysis Standards in Strong Tumors (RECIST 1.1) inside 12 months previous to screening. The first endpoint was progression-free survival, as assessed by blinded impartial central evaluation, or dying by any trigger. Secondary and exploratory endpoints embrace security and tolerability measures, goal response charge (ORR), period of response, modifications in tumor quantity assessed by magnetic resonance imaging (MRI), and modifications in patient-reported outcomes (PROs). DeFi consists of an open-label extension part, which is ongoing.

About Desmoid Tumors

Desmoid tumors are uncommon, aggressive, regionally invasive, doubtlessly morbid tumors of the delicate tissues.^2,3 Whereas they don’t metastasize, desmoid tumors are related to a excessive charge of recurrence.^3,4,5 Typically known as aggressive fibromatosis, or desmoid fibromatosis, these delicate tissue tumors may be severe, debilitating, and in uncommon instances when very important organs are impacted, they are often life-threatening.^3,6

Desmoid tumors are mostly recognized in sufferers between the ages of 20 to 44 years, with a two-to-three occasions greater prevalence in females.^5,7,8,9 It’s estimated that there are 1,000-1,650 new instances recognized per 12 months in america.^8,9,10

Traditionally, desmoid tumors have been handled with surgical resection, however this method has change into much less favored because of a excessive recurrence charge after surgical procedure.^2,5,11 There are at present no FDA-approved therapies for the therapy of desmoid tumors.

About Nirogacestat

Nirogacestat is an oral, selective, small molecule gamma secretase inhibitor in Part 3 medical improvement for desmoid tumors. SpringWorks can be evaluating nirogacestat as a possible therapy for sufferers with ovarian granulosa cell tumors and for sufferers with a number of myeloma as a part of a number of B-cell maturation agent (BCMA) mixture remedy regimens in collaboration with leaders in {industry} and academia. Nirogacestat is an investigational drug for which security and efficacy haven’t been established.

The U.S. Meals and Drug Administration (FDA) has accepted the New Drug Utility (NDA) for nirogacestat for the therapy of adults with desmoid tumors, which is being reviewed beneath the FDA’s Actual-Time Oncology Evaluate program. The NDA was granted Precedence Evaluate designation and has been given a Prescription Drug Consumer Payment Act (PDUFA) motion date of August 27, 2023. The FDA additionally granted Quick Observe and Breakthrough Remedy Designations to nirogacestat for the therapy of grownup sufferers with progressive, unresectable, recurrent or refractory desmoid tumors or deep fibromatosis. As well as, nirogacestat has acquired Orphan Drug Designation from the FDA for the therapy of desmoid tumors and from the European Fee for the therapy of sentimental tissue sarcoma.

Gamma secretase cleaves a number of transmembrane protein complexes, together with Notch, which is believed to play a task in activating pathways that contribute to progress of desmoid and ovarian granulosa cell tumors. Gamma secretase has additionally been proven to immediately cleave membrane-bound BCMA, ensuing within the launch of the BCMA extracellular area (ECD) from the cell floor. By inhibiting gamma secretase, membrane-bound BCMA may be preserved, growing goal density whereas decreasing ranges of soluble BCMA ECD, which can function decoy receptors for BCMA-directed therapies. Nirogacestat’s skill to boost the exercise of BCMA-directed therapies has been noticed in preclinical fashions of a number of myeloma. SpringWorks is evaluating nirogacestat as a BCMA potentiator and has a number of collaborations with industry-leading BCMA builders to guage nirogacestat in combos throughout modalities. SpringWorks has additionally fashioned analysis collaborations with Fred Hutchinson Most cancers Analysis Middle and Dana-Farber Most cancers Institute to additional characterize the power of nirogacestat to modulate BCMA and potentiate BCMA-directed therapies utilizing a wide range of preclinical a number of myeloma fashions.

About SpringWorks Therapeutics

SpringWorks is a clinical-stage biopharmaceutical firm making use of a precision medication method to buying, creating and commercializing life-changing medicines for sufferers dwelling with extreme uncommon illnesses and most cancers. SpringWorks has a differentiated focused oncology pipeline spanning stable tumors and hematological cancers, together with two late-stage medical trials in uncommon tumor sorts in addition to a number of packages addressing extremely prevalent, genetically outlined cancers. SpringWorks’ strategic method and operational excellence in medical improvement have enabled it to quickly advance its two lead product candidates into late-stage medical trials whereas concurrently coming into into a number of shared-value partnerships with innovators in {industry} and academia to unlock the total potential for its portfolio and create extra options for sufferers with most cancers. For extra data, go to www.springworkstx.com and comply with @SpringWorksTx on Twitter and LinkedIn.

SpringWorks Ahead-Wanting Statements

This press launch comprises “forward-looking statements” throughout the that means of the Non-public Securities Litigation Reform Act of 1995, as amended, referring to our enterprise, operations, and monetary situations, together with, however not restricted to, present beliefs, expectations and assumptions concerning the way forward for our enterprise, future plans and methods, our improvement plans, our preclinical and medical outcomes, in addition to referring to different future situations. Phrases reminiscent of, however not restricted to, “sit up for,” “consider,” “anticipate,” “anticipate,” “estimate,” “intend,” “plan,” “would,” “ought to” and “might,” and related expressions or phrases, establish forward-looking statements. New dangers and uncertainties might emerge every so often, and it’s not doable to foretell all dangers and uncertainties. Any forward-looking statements on this press launch are primarily based on administration’s present expectations and beliefs and are topic to quite a lot of dangers, uncertainties and essential components that will trigger precise occasions or outcomes to vary materially from these expressed or implied by any forward-looking statements contained on this press launch, together with, with out limitation, dangers referring to: (i) the success and timing of our product improvement actions, together with the initiation and completion of SpringWorks’ medical trials, (ii) the truth that topline or interim knowledge from a medical research might not be predictive of the ultimate or extra detailed outcomes of such research, or the outcomes of different ongoing or future research, (iii) the success and timing of our collaboration companions’ ongoing and deliberate medical trials, (iv) the timing of our deliberate regulatory submissions and interactions, together with the timing and consequence of selections made by the U.S. Meals and Drug Administration (FDA) and different regulatory authorities, investigational evaluation boards at medical trial websites and publication evaluation our bodies, (v) whether or not FDA or different regulatory authorities would require further data or additional research, or might fail or refuse to approve or might delay approval of our drug candidates, (vi) our skill to acquire and preserve regulatory approval of any of our product candidates, (vii) our plans to analysis, uncover and develop further product candidates, (viii) our skill to keep up enough patent safety and efficiently implement patent claims in opposition to third events, (ix) our skill to enter into collaborations for the event of latest product candidates, (x) our skill to ascertain manufacturing capabilities, and our and our collaboration companions’ skills to fabricate our product candidates and scale manufacturing, (xi) our skill to satisfy any particular milestones set forth herein, and (xii) uncertainties and assumptions concerning the impression of the COVID-19 pandemic on SpringWorks’ enterprise, operations, medical trials, provide chain, technique, targets and anticipated timelines.

Besides as required by relevant regulation, we don’t plan to publicly replace or revise any forward-looking statements contained herein, whether or not because of any new data, future occasions, modified circumstances or in any other case. Though we consider the expectations mirrored in such forward-looking statements are affordable, we can provide no assurance that such expectations will show to be appropriate. Accordingly, readers are cautioned to not place undue reliance on these forward-looking statements.

For additional data concerning the dangers, uncertainties and different components that will trigger variations between SpringWorks’ expectations and precise outcomes, you need to evaluation the “Danger Components” in Merchandise 1A of Half II of SpringWorks’ Quarterly Report on Kind 10-Q for the quarter ended March 31, 2023, in addition to discussions of potential dangers, uncertainties and different essential components in SpringWorks’ subsequent filings.

Contacts:

Kim Diamond
Vice President, Communications and Investor Relations 
Cellphone: 203-561-1646
E-mail: kdiamond@springworkstx.com

Samantha Hilson Sandler 
Senior Director, Investor Relations 
Cellphone: 203-461-5501 
E-mail: samantha.sandler@springworkstx.com

References

¹ Gounder M et al. Nirogacestat, a Gamma-Secretase Inhibitor for Desmoid Tumors. N Engl J Med 2023; 388:898-912. doi: 10.1056/NEJMoa2210140

² Kasper B, Baumgarten C, Garcia J, et al; Desmoid Working Group. An replace on the administration of sporadic desmoid-type fibromatosis: a European Consensus Initiative between Sarcoma PAtients EuroNet (SPAEN) and European Group for Analysis and Therapy of Most cancers (EORTC)/Delicate Tissue and Bone Sarcoma Group (STBSG). Ann Oncol. 2017;28(10):2399-2408.

³ Penel N, Chibon F, Salas S. Grownup desmoid tumors: biology, administration and ongoing trials. Curr Opin Oncol. 2017;29(4):268-274.

⁴ Xie Y, Xie Ok, Gou Q, He J, Zhong L, Wang Y. Recurrent desmoid tumor of the mediastinum: a case report. Oncol Lett. 2014;8(5):2276-2278.

⁵ Skubitz KM. Biology and therapy of aggressive fibromatosis or desmoid tumor. Mayo Clin Proc. 2017;92(6):947-964.

⁶ Joglekar SB, Rose PS, Sim F, Okuno S, Petersen I. Present views on desmoid tumors: the Mayo Clinic method. Cancers (Basel). 2011;3(3):3143-3155.

⁷ Penel N, Coindre JM, Bonvalot S, et al. Administration of desmoid tumours: a nationwide survey of labelled reference centre networks in France. Eur J Most cancers. 2016;58:90-96.

⁸ van Broekhoven DLM, Grünhagen DJ, den Bakker MA, van Dalen T, Verhoef C. Time tendencies within the incidence and therapy of extra-abdominal and stomach aggressive fibromatosis: a population-based research. Ann Surg Oncol. 2015;22(9):2817-2823.

⁹ Anneberg M, Svane H, Fryzek J, et al. The Epidemiology of Desmoid Tumors in Denmark. Most cancers Epidemiology. 2022; 77:1-7. doi.org/10.1016/j.canep.2022.102114.

¹⁰ Orphanet Report Sequence: Uncommon Ailments assortment. Prevalence and incidence of uncommon illnesses: bibliographic knowledge. Number one, January 2022. Accessed April 28, 2022. https://www.orpha.web/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf.

¹¹ The Desmoid Tumor Working Group. The administration of desmoid tumors: a joint international evidence-based consensus guideline method for grownup and pediatric sufferers. Accessed April 10, 2022. https://dtrf.org/wp-content/uploads/2020/02/Desmoid_Paper_2018_A4_RL_Web300-1.pdf.