METAP2

The FDA has approved the first treatment for hyperphagia, a condition which causes insatiable hunger and is associated with the rare genetic disorder Prader-Willi Syndrome (PWS). Since 2000, when the FDA approved recombinant human growth hormone (rhGH) for those with the rare genetic disorder Prader-Willi Syndrome (PWS), several companies have come up short in their attempts to develop a more advanced treatment for hyperphagia, an insatiable hunger condition associated with PWS.Wednesday, Soleno Therapeutics broke through with an FDA nod for Vykat XR (diazoxide choline), which becomes the first drug to treat hyperphagia. It is endorsed for those aged 4 years and older with the condition, which leaves patients with low muscle tone, short stature and intellectual and developmental problems.The once-daily extended-release tablet is a potassium channel activator. The channels, which are widespread throughout the body, including in the pancreas, regulate insulin secretion.With the approval, the share price of the 26-year-old Redwood, California, company had soared by 37% on Thursday morning.Based on the average weight of patients in its clinical trials, Soleno will charge $466,200 per year for Vykat XR. The company expects it to be available next month.In a release, Soleno CEO Anish Bhatnagar, M.D., called the approval “a significant milestone” for the company and for the “PWS community who have had no options to treat the most disruptive aspect of this disease.”Jennifer Miller, M.D., of the University of Florida and a principal investigator in the Vykat XR’s clinical development program, added that it will help families of those with PWS who “have been prisoners in their own homes because of the need to provide constant, eyes-on supervision 24/7 with access to food being completely restricted.”The approvel was backed by a phase 3 trial in which patients were observed during a 16-week withdrawal study after receiving Vykat XR for a median period of 3.3 years. Those who switched to placebo for the study period demonstrated a statistically significant worsening of hyperphagia compared to patients who remained on the drug.Over four years of data collected in four open-label studies, Vykat XR has shown a consistent safety profile with the most common adverse reactions—hypertrichosis, edema, hyperglycemia and rash—occurring in roughly 10% of the patients. The Prader-Willi Syndrome Association USA estimates that the disorder occurs in 1 in every 15,000 live births, with more than 300,000 people worldwide affected. Soleno says that claims data show there are 10,000 PWS patients in the U.S. Among the companies that have struck out in their attempts to develop a treatment for hyperphagia are Alize Pharma of France, which succeeded in a 2016 phase 2 study with AZP-531, a first-in-class unacylated ghrelin peptide analog, but failed to progress it further.In 2016, Boston-based Zafgen demonstrated the efficacy of beloranib, a MetAP2 inhibitor, in a phase 3 trial before the treatment was derailed by safety issues. Sweden’s Saniona developed Tesomet, a combination of monoamine reuptake inhibitor tesofensine and beta blocker metoprolol, which gained Orphan Drug designation from the FDA in 2021 before its development was halted a year later because of funding limitations.Acadia Pharmaceuticals of San Diego is developing a treatment, intranasal carbetocin, which the FDA rejected in 2022. Acadia gained the candidate through a $10 million acquisition of Chicago’s Levo Therapeutics.  

Seasoned advisory group including RNA, translation and commercialisation luminaries. LONDON, Jan. 10, 2025 /PRNewswire/ -- Serna Bio, an AI drug discovery company pioneering RNA-targeting small molecules, today announced the members of its Scientific Advisory Board (SAB). Established in 2021, Serna Bio is a preclinical drug discovery company with lead programs in neuro metabolism and obesity. The company is backed by leading investors including but not limited to, Y-combinator, Hummingbird Ventures, and 50Years. "We have established a truly differentiated platform to discover a novel class of small molecules - translational enhancers - and are using this to advance the development of therapies for diseases with no existing treatments, with a focus on genetically validated targets. The strength of our platform and IP has enabled us to surround ourselves with industry veterans with expertise in RNA Biology, preclinical RNA-small molecule research, clinical development and drug commercialisation. I am honoured to work with such an exceptional Scientific Advisory Board. They will be a force amplifier as we progress our lead assets toward the clinic and strengthen our pipeline," said Dr. Khan, MBA PhD. founder and CEO of Serna Bio The Scientific Advisory Board includes leading academics such as Dr. Nahum Sonenberg, who identified and characterized various translation factors involved in translation initiation; Dr. Matthew Hayes, a world leader in obesity drug discovery; and Dr. Jay Schneekloth, an expert in RNA small molecule development. It also includes industry leaders, including Jeff Ajer, the former Chief Commercial Officer at BioMarin. The advisors will draw on their considerable expertise and depth of experience to advise the company and its leadership team on scientific and strategic matters at the intersection of machine learning, RNA biology and drug discovery to help Serna Bio design next-generation small molecules to enhance translation for diseases caused by insufficient protein expression. "Serna Bio has developed a unique approach to biological translation via a large library of next-generation small molecules targeting RNA, with the potential to improve outcomes for patients with a range of diseases otherwise not addressed by present therapies." said Giorgio Massimini, MD, "I am excited to work closely with Dr. Khan and her leadership team as the company builds on its discoveries and pursues its clinical aspirations." "Many patients with rare genetic diseases continue to lack treatment options. With Serna Bio's ability to enhance translation, the company is opening up a new mechanism of action, enabling the development of much-needed medicines for the treatment of previously intractable diseases" said Nick France, MD The full SAB comprises: Jay Schneekloth Senior Investigator at National Cancer Institute (NCI). A pioneer in the identification of selective RNA and DNA binding small molecules. His work has led to the discovery that RNA targeting, druglike compounds are suitable starting points for inhibitor discovery efforts while driving fundamental advances in understanding RNA-small molecule recognition. Giorgio Massimini formerly Vice President Merck KGaA. Over 30 years of experience in leading clinical research & development projects. He contributed to the development of MEK inhibitors, c-Met inhibitors, IDO/TDO inhibitors, MetAP2 inhibitors, DNA repair inhibitors, monoclonal antibodies and other tyrosine kinase inhibitors in the Merck Biopharma pipeline. Nahum Sonenberg James McGill professor of biochemistry at McGill University in Montreal, Quebec, Canada. He is best known for his seminal contributions to our understanding of translation and is notable for the discovery of the mRNA 5' cap-binding protein, eIF4E, the rate-limiting component of the eukaryotic translation apparatus. Nick France Vice President, Global Therapeutic Area Head for Genomic Medicines and Neurology at Alexion. A physician-scientist and rare disease drug development leader. He has worked across the biopharma ecosystem developing diverse therapies for rare disease. Jeff Ajer formerly Executive Vice President and Chief Commercial Officer at BioMarin. Mr. Ajer has more than 25 years of experience driving commercialisation for rare diseases and speciality medicines. He was integral in establishing BioMarin's commercial infrastructure and global footprint and played a leadership role in the launches and growth strategies for BioMarin's commercial brands. Emily Freeman Senior Director, Global Medical Affairs, Patient Focused Implementation Science at Gilead Sciences. She is interested in the development of evidence-based communication tools to facilitate shared decision-making for patients. She has experience at Bristol-Myers Squibb, Pfizer, Eli Lilly, AbbVie, and most recently Sanofi. Matthew Hayes Albert J Stunkard Professor in Psychiatry at the University of Pennsylvania and Vice Chair for Basic and Translational Neuroscience Research in the Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania. Dr. Hayes is considered a leading expert on the neuroendocrine systems that regulate energy balance. About Serna Bio Serna Bio is an AI-enabled drug discovery company developing the next generation of small molecules to enhance translation. By targeting functional RNA structures, the company's proprietary discovery platform enables selective upregulation of the production of a protein of interest, using orally bio-available small molecules. Serna Bio's approach is a paradigm shift in drug discovery, moving from classical "inhibition" of protein function to protein enhancement. This novel approach unlocks the potential to treat a range of diseases intractable by classical drug discovery. The company's programs are powered by a Generative AI discovery platform trained on proprietary RNA-small molecule datasets, enabling Serna Bio to generate molecules in novel chemical space, outperforming state-of-the-art methods such as NVIDIA MolMIMM for small molecules targeting RNA. For more information about Serna Bio, please visit the company website at serna.bio or follow us on LinkedIn. 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1. Asieris Pharmaceuticals: APL-1202Indication: non-muscle invasive bladder cancer (NMIBC) On February 5th, Asieris Pharmaceuticals announced that its product APL-1202, when used in combination with chemotherapy instillation to treat recurrent intermediate to high-risk non-muscle invasive bladder cancer (NMIBC), failed to meet the primary endpoint in a randomized, double-blind, controlled, multicenter pivotal clinical trial. Consequently, the company has decided to discontinue the further development of APL-1202 in combination with chemotherapy instillation for this indication. APL-1202 is an orally-administered, reversible MetAP2 inhibitor with anti-angiogenic, anti-tumor activities, and the capability to modulate the tumor immune microenvironment. The study in question was a randomized, double-blind, controlled, multicenter pivotal clinical trial with the primary endpoint being event-free survival (EFS), where an "event" is defined as pathologically-confirmed recurrence, progression, or death caused by bladder cancer. The results indicated that although a trend toward effectiveness was observed in certain patient subgroups, the primary efficacy parameter of event-free survival (EFS) did not meet the pre-specified statistical hypothesis. In addition to this study, the company is also conducting two other clinical trials with APL-1202. The Phase III clinical trial (Ascertain) of APL-1202 as a monotherapy for the treatment of untreated intermediate-risk NMIBC is currently in the patient enrollment phase. The Phase II clinical trial (Anticipate) of oral APL-1202 in combination with atezolizumab as a neoadjuvant treatment for muscle-invasive bladder cancer (MIBC) has completed enrollment of all participants, with the expectation to report top-line data from the Phase II trial in the third quarter of 2024. The interim analysis of the Anticipate study has already been conducted, and the results have met the pre-set requirements of the protocol. 2. Lilly: VerzenioIndication: metastatic castration-resistant prostate cancer (mCRPC) Clinical Trials: Phase 3 On February 6, Lilly reported that Verzenio did not meaningfully extend survival without cancer progression or death in mCRPC patients when combined with Johnson & Johnson's Zytiga and prednisone, as seen in their Q4 financial update. Despite the phase 3 CYCLONE-2 trial setback, Verzenio continues to hit sales records, with $1.15 billion in Q4 revenue. This occurs as it prepares to compete with Novartis' Kisqali in early breast cancer, which contributed to Verzenio's 56% revenue increase in 2023. 3. Gilead: magrolimabIndication: Acute Myeloid Leukemia (AML) Clinical Trials: Phase 3 On February 7th, Gilead announced the termination of the Phase 3 ENHANCE-3 study of the CD47 monoclonal antibody magrolimab for the treatment of Acute Myeloid Leukemia (AML). The FDA has placed all magrolimab studies, including those for Myelodysplastic Syndromes (MDS) and AML as well as related expanded access programs, under full clinical hold. These decisions were made following recommendations from an independent Data Monitoring Committee, which reviewed preliminary data from a planned interim analysis of Overall Survival (OS) in the ENHANCE-3 trial. In this analysis, magrolimab, in combination with azacitidine and venetoclax, showed no therapeutic benefit and an observed increase in the risk of death, primarily due to infections and respiratory failure. Preliminary analyses of data from the other two clinical trials for high-risk MDS (ENHANCE) and TP53-mutant AML (ENHANCE-2) also indicated an increased risk of death in patients treated with magrolimab, as well as no therapeutic benefit. Based on these outcomes, Gilead has stated that they will no longer pursue the development of magrolimab for hematologic diseases. 4. Synlogic: SYNB1934Indication: Phenylketonuria (PKU) Clinical Trials: Phase 3 On February 8th, Synlogic announced the termination of the Synpheny-3 study, a Phase III clinical trial investigating labafenogene marselecobac (SYNB1934) as a potential treatment for Phenylketonuria (PKU). SYNB1934 is a bacterial strain engineered using synthetic biology to degrade phenylalanine. The decision to terminate the Synpheny-3 trial was based on the results of an internal review conducted prior to the upcoming evaluation by an independent Data Monitoring Committee (DMC), which indicated that the trial was unlikely to meet its primary endpoint. This decision was not based on concerns about safety or tolerability. Synlogic will now work with the clinical trial sites involved with Synpheny-3 to carry out the decision to terminate the trial. 5. AstraZeneca: TozorakimabIndication: diabetic kidney disease Clinical Trials: Phase 2b On February 8th, AstraZeneca announced during their annual report for the year 2023 that they have decided to discontinue the Phase IIb clinical trial (NCT04170543) of the anti-IL-33 monoclonal antibody Tozorakimab in combination with dagliflozin for the treatment of diabetic kidney disease due to insufficient efficacy. The study aimed to evaluate the effectiveness and safety of MEDI3506 on top of standard care in patients with diabetic kidney disease. The primary objective was to assess the impact of MEDI3506 on albuminuria in adult participants with diabetic kidney disease, whereas the secondary objectives included evaluating safety, pharmacokinetics (PK), and the incidence of Anti-Drug Antibodies (ADA) during treatment. 6. CSL: CSL112Indication: major adverse cardiac events (MACE) Clinical Trials: Phase 3 On February 11th, CSL announced that the Phase III AEGIS-II trial of CSL112 did not meet its primary endpoint of reducing the risk of major adverse cardiac events (MACE) in post-acute myocardial infarction (AMI) patients. 7. AN2 Therapeutics: epetraboroleIndication: Refractory Mycobacterium avium complex (MAC) lung disease Clinical Trials: Phase 3 On February 12th, AN2 Therapeutics announced a voluntary pause in patient enrollment for the Phase III segment of its seamless Phase II/III clinical trial (EBO-301), which aims to evaluate the efficacy and safety of the oral small-molecule bacterial leucyl-tRNA synthetase inhibitor, epetraborole, for the treatment of refractory lung disease caused by Mycobacterium avium complex (MAC). This double-blind, placebo-controlled clinical trial is divided into two cohorts that compare the effectiveness of epetraborole combined with an optimized background regimen (OBR) versus placebo plus OBR. The Phase II segment of the study completed enrollment of 80 patients in September 2023, and to date, nearly 100 patients have been recruited in the Phase III portion. Enrolled patients will be allowed to continue participating in the study. After conducting a blinded pooled analysis of the ongoing Phase II research, the observed efficacy was potentially lower than expected, leading to the decision to voluntarily suspend the trial. This decision was not based on safety concerns; rather, the purpose of the Phase II trial was to lay the groundwork for the Phase III study. The company expects to present preliminary data from the Phase II trial in the summer of 2024. 8. Otsuka Pharmaceutical: AVP-786Indication: agitation associated with Alzheimer's disease dementia Clinical Trials: Phase 3 On February 12th, Otsuka Pharmaceutical announced that the Phase III clinical trial (NCT03393520) of AVP-786 (deuterated dextromethorphan + quinidine) for treating agitation associated with Alzheimer's disease dementia failed to meet its primary efficacy endpoint. AVP-786 is a combination formulation of deuterated dextromethorphan hydrobromide and the CYP2D6 inhibitor, quinidine sulfate. It has been observed that deuteration significantly reduces sensitivity to metabolism by the cytochrome P450 (CYP2D6) enzyme, thereby improving bioavailability. Regarding the primary efficacy endpoint, there was no statistically significant difference between AVP-786 and placebo in the average change from baseline in the total score on the Cohen-Mansfield Agitation Inventory (CMAI) at week 12. 9. Roivant Sciences: RVT-2001Indication: myelodysplastic syndromes (MDS) Clinical Trials: Phase 1/2 On February 13th, Roivant Sciences disclosed in its financial report that it has terminated the clinical Phase I/II trial of the SF3B1 modulator RVT-2001 for the treatment of myelodysplastic syndromes (MDS), due to interim analysis results that did not meet the expected efficacy. In 2022, Roivant entered into a licensing agreement with Eisai to acquire the global exclusive rights to the investigational drug RVT-2001, which is a potential first-in-class oral small molecule that modulates the splicing factor SF3B1. RVT-2001 has already demonstrated in a cohort of 19 low-risk, transfusion-dependent MDS patients, that it can achieve transfusion independence in over 30% of those patients. 10. Denali/ Sanofi: DNL788Indication: Amyotrophic Lateral Sclerosis (ALS) Clinical Trials: Phase 2 On February 16th, Denali Therapeutics disclosed in a SEC filing that the Phase II HIMALAYA study of DNL788 (SAR443820) for the treatment of Amyotrophic Lateral Sclerosis (ALS) failed to meet the primary endpoint of significant improvement in the scores of the Revised ALS Functional Rating Scale (ALSFRS-R). As a result of this news, Denali's stock price fell by nearly 8%. In October 2018, Sanofi and Denali embarked on an expansive collaboration for the global development and commercialization of RIPK1 inhibitors. Sanofi is leading the Phase I and Phase II clinical development of SAR443820/DNL788 for the treatment of ALS and Multiple Sclerosis (MS), and is collaborating with Denali on Phase III clinical trials for the treatment of ALS, MS, and Alzheimer’s disease. SAR443820/DNL788 is an effective, selective, and brain-penetrant RIPK1 inhibitor co-developed by Sanofi and Denali. Sanofi will continue the K2 Phase II study of SAR443820/DNL788 in patients with Multiple Sclerosis; on January 8, Denali revealed in a press release that Sanofi had completed a Phase II trial of SAR443820/DNL788 for the treatment of Multiple Sclerosis (MS), recruiting a total of 174 participants. 11. Palatin: PL9643Indication: Dry Eye Disease (DED) Clinical Trials: Phase 3 On February 28th, Palatin announced the results of its pivotal Phase 3 clinical trial for PL9643, MELODY-1, which evaluated the safety and efficacy of PL9643 compared to vehicle in the treatment of Dry Eye Disease (DED). MELODY-1 had two co-primary endpoints for efficacy: one clinical symptom (pain) and one clinical sign (conjunctival lissamine green staining), as well as multiple secondary endpoints for other symptoms and signs of DED. The treatment duration was 12 weeks, with a 4-week run-in period. Data analysis indicated that preliminary statistical analysis had to consider both age and gender (60% of the subjects were over 60 years old; 68% of the subjects were female). After adjusting for age and gender in the intent-to-treat (ITT) analysis, PL9643 treatment demonstrated statistically significant results with clinical relevance (a >10 point reduction in Visual Analogue Scale from baseline) and pain, the co-primary symptomatic endpoint (p<0.025), as well as several other symptomatic endpoints. PL9643 treatment showed a positive treatment effect above vehicle for the co-primary sign endpoint and secondary sign endpoints in the ITT population, but did not reach statistical significance. In the unadjusted planned analyses, the co-primary and secondary endpoints did not reach statistical significance.