Q4 2023 Earnings Summary
- Strong progress in the PRECISION 1 trial targeting TSC1 and TSC2 mutations, with full enrollment expected by May and the next interim readout in Q3 2024. This trial addresses a potential multibillion-dollar addressable market, targeting genetic alterations present in approximately 16,000 new patients annually in the U.S. alone.
- Enrollment is underway for Phase II trials in neuroendocrine tumors (NETs) and advanced endometrial cancer, with initial data expected later this year. These trials could expand the use of nab-Sirolimus into additional mTOR-driven cancers, demonstrating its versatility and potential for best-in-class efficacy.
- Ongoing collaboration with Mirati (now Bristol) combining nab-Sirolimus with adagrasib (KRAS inhibitor) continues, potentially expanding the use of the drug in combination therapies targeting KRAS-mutated cancers.
- FYARRO sales have stabilized around $6 million to $6.5 million per quarter, and the company expects this trend to continue in 2024, indicating potential market saturation in the ultra-rare PEComa indication and limited revenue growth from this product.
- The TSC2 arm of the PRECISION 1 trial reported lower response rates that are challenging to interpret due to heavily pretreated patients, raising concerns about nab-Sirolimus's efficacy in TSC2-mutated cancers and the potential impact on the anticipated multibillion-dollar market.
- Key clinical trial data from the PRECISION 1 trial will not be fully available until early 2025, delaying potential positive catalysts and extending the period of uncertainty, which could impact investor confidence and the company's valuation in the near term.
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PRECISION 1 Trial Progress
Q: Update on PRECISION 1 trial patient enrollment and dynamics?
A: The first 40 patients in the PRECISION 1 trial were heavily pretreated, having received three or more prior lines of therapy. We anticipate continuing to enroll later-line patients as per the trial design. While we cannot comment on the overall patient population yet, enrollment is ongoing, and we plan to report the total 80 patients at the 2/3 interim later this year. -
FYARRO Sales Outlook
Q: Guidance or commercial plan for FYARRO sales in the coming year?
A: We are not providing specific guidance for this year. Sales have stabilized around $6 million to $6.5 million per quarter in the last few quarters. We expect similar sales for 2024, continuing at this level. FYARRO remains the preferred therapy for PEComa, but the market is ultra-rare, and we may be reaching saturation. -
FDA Considerations for Tumor-Agnostic Indication
Q: What is crucial for FDA when considering tumor-agnostic labeling?
A: The FDA wants to see a variety of different tumor types represented, avoiding concentration in certain subtypes. They look for a representation of the mutation across various tumor types. A reasonable response rate and a good safety profile are important. Since we have approval in a single indication, the FDA will look for consistency in the safety profile in the agnostic population. -
Data from Endometrial and NET Studies
Q: When can we expect initial data from endometrial or NET studies?
A: We potentially plan to share data on the endometrial and neuroendocrine trials later this year. Both studies are actively enrolling patients with good engagement. For the endometrial study, it's an open-label Phase II combining nab-Sirolimus with letrozole in patients with advanced or recurrent endometrial carcinoma who have received no or one prior line of chemotherapy. We anticipate reporting early results by the end of this year. -
Adagrasib Combo Trial Status
Q: Any updates on the adagrasib combination trial, especially after Bristol's acquisition of adagrasib?
A: The collaboration with Mirati (now Bristol) continues and is ongoing. We are enrolling patients into the trial but have no further updates at this point. -
Other mTOR-Sensitive Mutations
Q: Beyond TSC1/2, which mutational backgrounds are sensitive to mTOR inhibitors?
A: There are many mutations along the mTOR pathway that may provide targets. However, none have been specifically identified as a mutational target for mTOR inhibition. There are suggestions, but none are proven.