TSC1

Combined pipeline and head count changes announced yesterday are expected to extend Aadi Bioscience’s cash runway into “at least” the second half of 2026. Aadi Bioscience’s Fyarro is on track to fail a phase 2 solid tumor trial, leading the biotech to halt the study and lay off 80% of its R&D workforce.The company had been investigating the approved mTOR inhibitor, also known as nab-sirolimus, in the midstage PRECISION1 study in mTOR inhibitor-naïve malignant solid tumors harboring TSC1 or TSC2 inactivating alterations. But Aadi revealed yesterday that the independent data monitoring committee had decided the trial was unlikely to hit its key goal—namely exceeding an efficacy threshold necessary to support an accelerated approval.It marks a significant setback for Aadi’s wider hopes for Fyarro, the only drug in its pipeline. Only two weeks ago, the California-based company had been suggesting that the data from PRECISION1 had “the potential to demonstrate a meaningful impact on the lives of patients who have already received standard therapies appropriate for their tumor type and stage of disease.”"We are humbled by the effort of the investigators, support staff, and most importantly, the patients and their families who took part in PRECISION1,” Aadi CEO Dave Lennon said in the post-market Aug. 20 release.“While nab-sirolimus showed monotherapy activity in the study population, the trial fell short of delivering what we believe would be required to support an accelerated approval in the broad TSC1/TSC2 inactivating mutations indication,” Lennon added. “We look forward to providing the full trial analysis at a later date.” Aadi has also been evaluating Fyarro in two other phase 2 studies for difficult-to-treat mTOR-driven cancers: neuroendocrine tumors of the lung, gastrointestinal tract and pancreas; and advanced or recurrent endometrioid-type endometrial cancer in combination with Novartis’ Femara.While Aadi is halting the PRECISION1 trial, it said it will continue dosing patients in the neuroendocrine tumor and endometrial cancer studies, although it will stop enrolling new patients. With 10 and 20 patients enrolled in those studies, respectively, Aadi thinks it has enough participants to assess the drug’s efficacy later this year.In relation to this decision, the biotech will lay off 80% of its R&D staff. Fierce has asked Aadi how many employees are set to be impacted.The company had $78.6 million to hand as of the end of June, when it anticipated the money would last into the final months of 2025. The combined pipeline and head count changes announced yesterday are expected to extend the company’s cash runway into “at least” the second half of 2026, it said.As well as “preserving cash” by canning or halting enrollment in its remaining Fyarro trials, Aadi said its other primary focus will be “maximizing its commercial business” through sales of Fyarro in its approved indication of perivascular epithelioid cell tumor. These sales brought in $6.2 million for the company in the second quarter.

Aadi Bioscience is cutting the majority of its research staff as a mid-stage study intended to support expanded approval of Fyarro (nab-sirolimus) is unlikely to meet its efficacy goal. CEO David Lennon explained that while the mTOR therapy demonstrated activity, it “fell short of delivering what we believe would be required to support an accelerated approval in the broad TSC1/TSC2-inactivating mutations indication.”The PRECISION1 trial was designed to enrol around 120 mTOR inhibitor-naïve patients with solid tumours harbouring pathogenic inactivating alterations in either TSC1 or TSC2 genes. An interim analysis conducted at the end of last year in the first 40 participants had shown sustained tumour reductions, including a 26% overall response rate (ORR) in the TSC1 arm, and an 11% ORR in the TSC2 cohort.However, Aadi said the most recent analysis by the study’s independent data monitoring committee suggests that the trial results are unlikely to support an accelerated FDA approval. The company added that about 25 patients in PRECISION1 who are still benefiting from Fyarro will be eligible for transition to a planned expanded access protocol.As such, Aadi will focus efforts and resources on marketing Fyarro – which is authorised in the US for adults with locally advanced, unresectable or metastatic malignant perivascular epithelioid cell tumour (PEComa) – and halt enrolment in further studies of the drug. These include two Phase II trials for advanced or recurrent endometrioid-type endometrial cancer and neuroendocrine tumours, which have both recruited enough patients to assess initial efficacy signals later this year.According to Aadi, the pipeline adjustments will lead to the loss of 80% of its R&D workforce, with its overall actions extending cash into at least the second half of 2026. Lennon added that the company has also “hired an advisory firm to explore all options to maximise value for shareholders."

-- Top-line results from Phase 2B study expected in first quarter of 2025 -- Aug. 13, 2024 -- Noema Pharma AG, a clinical-stage biotech company targeting debilitating neuroscience-based disorders with first-in-disease therapeutic approaches, today announced the completion of enrollment in the GALENE Phase 2B trial, a double-blind, placebo-controlled trial evaluating the efficacy of NOE-101 for seizure control in tuberous sclerosis complex (TSC). "We are pleased to have completed enrollment in our Phase 2B study of NOE-101,” said Ilise Lombardo, MD, Chief Executive Officer for Noema. “NOE-101 has the ability to decrease neuronal excitability with the potential to address important therapeutic needs for patients with TSC with a novel mechanism of action. With the trial fully enrolled, we look forward to reporting top-line data in the first quarter of next year.” Dr. Mustafa Sahin, MD, Associate Chief of Research, Department of Neurology; Managing Director, Rosamund Stone Zander Translational Neuroscience Center and Director, Translational Research Program at Boston Children's Hospital added, “TSC is a debilitating disease characterized by serious, life-threatening seizures that have long-term impact on brain development. Since current antiepileptic therapies have limited efficacy and significant side effects with over 60% of patients refractory to current treatments, the need for new treatments remains strong.” Dr. Sahin added, “This need underscores the importance of studying medications like NOE-101 with distinct mechanisms of action.” The Phase 2B GALENE study (NOE-TSC-201) is a multicenter, 30-week randomized, double-blind, placebo controlled, cross-over study evaluating the efficacy and safety of NOE-101 adjunctive to ongoing antiseizure therapy in patients with uncontrolled seizures associated with TSC. The primary endpoint will assess improvement in seizure frequency for the NOE-101 treatment and placebo treatment periods. Patients who complete the GALENE study may continue to a 52-week open-label extension. NOE-101, or basimglurant, is a potent inhibitor of metabotropic glutamate receptor 5 (mGluR5). It is also currently under clinical investigation for trigeminal neuralgia. Tuberous sclerosis complex is a rare genetic multisystem disorder caused by mutations in TSC1 and TSC2 genes. This disorder causes uncontrolled benign tumor growth in vital organs of the body including the brain, skin, heart, eyes, kidneys, and lungs and is the leading cause of genetic epilepsy. Approximately 80,000 people in the US and EU are diagnosed with TSC, and about 60 percent of patients do not respond to current treatment options. Their treatment-resistant seizures are often serious or life threatening. Noema Pharma is a clinical-stage biotech company advancing a portfolio of transformative therapeutics utilizing first-in-disease approaches targeting orphan and large neuroscience-based indications with high unmet need. Noema has active Phase 2 clinical trials evaluating pain in trigeminal neuralgia, seizures in tuberous sclerosis complex, Tourette syndrome and vasomotor symptoms due to menopause. Noema was founded by leading venture capital firm Sofinnova Partners and is supported by current investors including Forbion, Gilde Healthcare, Invus, Jeito Capital, Polaris Partners and UPMC Enterprises. Learn more at www.noemapharma.com. The content above comes from the network. if any infringement, please contact us to modify.