Navitor Pharmaceuticals, Inc.

iStock, Nazan Akpolat After SPN-820’s failure, Supernus is relying on its non-stimulant ADHD drug Qelbree and the recently approved Parkinson’s therapy Onapgo to sustain the company. Supernus Pharmaceuticals’ drug candidate for treatment-resistant depression missed its primary endpoint in a Phase IIb study, the biotech revealed Tuesday. Patients on SPN-820, an oral activator of the mTORC protein, saw a 12.3-point improvement in their scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) at four weeks. Over the same time span, MADRS scores improved by 11.9 points in placebo comparators. The between-group difference failed to reach statistical significance, according to Supernus’ press announcement. Similarly, “there was no treatment difference” between the investigational treatment and placebo in terms of secondary endpoint, the biotech added. Supernus was down around 20% before the opening bell on Wednesday, as per SeekingAlpha . Analysts at Jefferies anticipated the selloff, writing to investors on Tuesday evening that “we see [Supernus] trading down -25%” due to the readout. CEO Jack Khattar in a statement said that the company is “disappointed” by these results, adding that it will “continue to analyze these data” and assess the path forward for SPN-820 with its development partner Navitor Pharmaceuticals. SPN-820’s failure is somewhat surprising given that the drug candidate in October 2024 aced a Phase II study in major depressive disorder. When taken once every three days as an adjunct to baseline antidepressant medication, SPN-820 elicited a “clinically meaningful improvement” as early as four hours after dosing when measured using MADRS. At the time, however, Jefferies cautioned that drugs that could work for both major depressive disorder and treatment-resistant depression are “rare”—a point the firm reiterated in its note on Tuesday. Despite the mid-stage stumble, Jefferies still sees some reasons to be positive about Supernus’ prospects, particularly with the “continued uptake” of its non-stimulant ADHD drug Qelbree. “Emphasis for [Supernus] will be on growing its core business moving forward.” In the near-term, Jefferies anticipates Qelbree to surpass its fourth-quarter 2024 sales consensus, putting it on-track to meet Jefferies’ projection of at least $500 million in peak sales for Supernus. A little further out is the recently approved apomorphine hydrochloride injection Onapgo for advanced Parkinson’s disease, which Jefferies expects could be “another potential growth driver for 2025-26” once it launches. Onapgo opens a $100 million to $300 million opportunity for Supernus, according to the analyst.

The Phase IIb study enrolled 250 adult patients with treatment-resistant depression. Credit: Justin Paget via Getty Images. Supernus Pharmaceutical’s stock declined following the release of disappointing Phase IIb trial results for SPN-820, an investigational treatment for adults with treatment-resistant depression (TRD). The company announced on 18 February that the trial did not meet its primary endpoint measured by a depression rating scale, with no statistically significant difference observed between the treatment and placebo groups. Supernus’ stock is down 17% from the close on 18 February to open on 19 February. The Phase IIb study (NCT05066672) enrolled 250 adult patients with TRD, who were randomised to receive either two or four 400mg doses of SPN-820 daily. After four weeks, patients receiving SPN-820 showed a 12.3-point reduction on the Montgomery-Åsberg Depression Rating Scale (MADRS), which assesses depression severity. However, the placebo group experienced an 11.9-point reduction, meaning the difference between the groups was not statistically significant. Supernus also reported no statistically significant differences in secondary endpoints. SPN-820, a mechanistic target of rapamycin complex 1 (mTORC1) activator, previously demonstrated promising results in an open-label Phase IIa trial (NCT06235905) conducted in patients with major depressive disorder (MDD). In that study, the drug showed a clinically meaningful improvement of -6.1 on the Hamilton Depression Rating Scale-6 items (HAM-D6) at two hours, improving to -9.6 by day ten. Suicidal ideation decreased by 80%, from 12.5% at baseline to 2.6% on day ten. In an October 2024 conference call, Supernus’s CMO Jonathan Rubin said the company would decide which indication to pursue further out of MDD or TRD based on the yet-to-be-unveiled latest Phase IIb data for the latter indication. Supernus licensed SPN-820 from Navitor Pharmaceuticals in 2020. The agreement included a $10m upfront payment and a $15m investment, with total potential payments exceeding $400m if all milestones are met. “We are disappointed that the trial did not meet its primary endpoint in this patient population,” said Supernus CEO Jack Khattar, who added that the company will continue to analyse the data and will discuss the future of the programme with Navitor. SPN-820 is not the only candidate in Supernus’s pipeline, should the company decide not to press ahead with its further development. The developer also has SPN-817, a reversible acetylcholinesterase inhibitor being developed for severe epilepsy. The candidate demonstrated positive results in an open-label Phase IIa trial (NCT05518578) and is currently being investigated in a larger placebo-controlled Phase II trial (NCT06798896). The standard of care for major depressive disorder (MDD) typically involves selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) as first-line treatments, often in combination with psychotherapy. However, these therapies can take weeks to take effect, and many patients do not respond adequately, leading to a need for innovative alternatives. Last month, Johnson & Johnson’s (J&J) nasal spray Spravato (esketamine) received a label expansion as a monotherapy treatment for MDD in adults who do not respond to two oral antidepressants. The US Food and Drug Administration’s (FDA) decision made Spravato the first-ever standalone treatment for adults with treatment-resistant depression.

– EKZ-102 is in IND-enabling development for the treatment of ALS and other neurodegenerative diseases, with a first-in-human clinical study planned for 2025 – Company welcomes new executive and Board appointments CAMBRIDGE, MA, USA I December 10, 2024 I Eikonizo Therapeutics, a biopharmaceutical company dedicated to developing disease-modifying therapies to improve the lives of people impacted by neurodegenerative and cardiorenal diseases announced today that it has secured an undisclosed equity investment from Novo Nordisk through its Science2Medicine iNNvest initiative . In addition to supporting the development of Eikonizo’s lead candidate, EKZ-102, a potential first-in-class, oral, CNS-penetrant, highly selective histone deacetylase 6 (HDAC6) inhibitor, the Novo Nordisk investment will also enable the advancement of novel Eikonizo HDAC6 inhibitors as potential disease-modifying therapeutics for cardiorenal disease. “I look forward to working with the Eikonizo team as they advance EKZ-102 into clinical studies. The program fits well with the company’s mission to bring disease-modifying therapies to help people living with neurodegenerative and cardiorenal diseases.” Concurrent with its investment, Miriam Frieden, Novo Nordisk’s Corporate Vice President of Early Innovation, Outreach and Alliances will join Eikonizo’s Board of Directors as a non-voting observer and Professor Bill Haynes, Scientific Corporate Vice President, Global Drug Discovery, Novo Nordisk, will join Eikonizo’s Scientific Advisory Board. “We are very proud to support promising early-stage companies like Eikonizo with its novel approach to HDAC6 inhibition as potential treatments for people living with serious chronic diseases,” said Miriam Frieden. “EKZ-102 is a highly selective, uniquely CNS-penetrant HDAC6 inhibitor with strong potential to be a first-in-class, disease-modifying therapy for ALS and other indications. This investment by Novo Nordisk through its iNNvest program will help accelerate EKZ-102 toward clinical proof of concept with a first-in-human clinical study planned in 2025,” said Rick Lundberg, President and CEO of Eikonizo. “We are equally excited to welcome several new team members with extensive industry experience, who will be instrumental in progressing EKZ-102 to clinical proof of concept and realizing the broad potential of our approach to HDAC6 inhibition for serious neurodegenerative and cardiorenal diseases.” Eikonizo also announced key additions to strengthen its leadership with the appointment of Thomas E. Hughes, PhD, Chairperson and Chief Executive Officer of Navitor Pharmaceuticals, to its Board of Directors, as well as Richard A. Fisher, PhD, as Chief Scientific Officer, Jim Luterman, PhD, as Executive Vice President of Development and Jon Graves, CPA as Vice President, Finance and Controller. “Eikonizo has established a compelling path forward for their novel HDAC6 inhibitors, and I’m honored to join the board at such a transformative time for the company,” said Tom Hughes. “I look forward to working with the Eikonizo team as they advance EKZ-102 into clinical studies. The program fits well with the company’s mission to bring disease-modifying therapies to help people living with neurodegenerative and cardiorenal diseases.” Thomas E. Hughes, PhD has over 30 years of industry experience in the development and commercialization of pharmaceutical products, currently serving as Chairperson and CEO of Navitor Pharmaceuticals and previously leading Zafgen as President and CEO as well as Chief Scientific Officer. Prior to Zafgen, Dr. Hughes held several positions at Novartis including Global Head of the Cardiovascular and Metabolic Diseases Therapeutic Area at the Novartis Institutes for BioMedical Research. Dr. Hughes currently serves as a member of the Board of Directors of Totus Medicines and is a member of scientific and strategic advisory boards including Ambrosia Biosciences and Broadview Ventures. He holds a PhD in nutritional biochemistry from Tufts University, an M.S. in zoology from Virginia Polytechnic Institute & State University and a B.A. in biology from Franklin and Marshall College. Rich Fisher, PhD, brings over 40 years of biotech scientific leadership experience to Eikonizo, including serving as CSO at LuMind IDSC, Vigil Neuroscience, Proclara Biosciences and Ikano Therapeutics, SVP of R&D at GlycoFi, VP of Research at UCB Pharma and CytoMed, and Director, Molecular Biology at Biogen. Rich received his BA in zoology and PhD in microbiology and molecular genetics from the University of Iowa and UI College of Medicine, respectively, after which he was an American Cancer Society Fellow during his postdoctoral training at the University of Chicago. Rich’s drug discovery and research experience covers multiple therapeutic areas and modalities. Jim Luterman, PhD brings over 25 years of biotech program leadership experience to Eikonizo, including serving as SVP and Head of Early-stage Development and Partnering at Enzyvant, EVP of R&D at OvaScience, Program Executive and Early Development Team Leader at Shire HGT, Program Leader at CombinatoRx and Manager of New Product Commercialization at Biogen Idec. Before joining industry, Jim was a Senior Analyst at Decision Resources and a Research Assistant at Brigham and Women’s Hospital. He received his BA in Biology and Psychology from Bucknell University, his PhD in Molecular Neuroscience from Rutgers University and conducted his postdoctoral fellowship at the Icahn School of Medicine at Mount Sinai. Jon Graves, CPA brings over 20 years of biopharma finance leadership experience to Eikonizo, including serving as VP of Finance at OncXerna Therapeutics, VP of Financial Operations at Corindus Vascular Robotics, Controller, North America at Sobi, Controller at Thermo Fisher Scientific, Finance Manager at Epix Pharmaceuticals and Senior Auditor at Arthur Andersen. Jon received his BS in Accounting at Providence College and is a licensed CPA. About EKZ-102 Eikonizo’s lead development candidate, EKZ-102, is a first-in-class, oral, small molecule HDAC6 inhibitor with the distinctive combination of high potency, selectivity and CNS penetrance necessary to protect neuronal function while minimizing potential off-target side effects to achieve a favorable safety and tolerability profile. EKZ-102 is in IND-enabling development for the treatment of ALS with planned expansion to other neurodegenerative disorders. About Eikonizo Therapeutics Eikonizo is developing novel, disease-modifying small molecule therapeutics targeting histone deacetylase 6 (HDAC6) to improve the lives of people impacted by neurodegenerative and cardiorenal diseases. Our dual mechanism approach to HDAC6 inhibition is designed to synergistically target key drivers of neurodegenerative and cardiorenal disease biology. SOURCE: Eikonizo Therapeutics