WDAY

• Travere Therapeutics Partnership: Everest Medicine has closed a global partnership with Travere Therapeutics for Siviributinib (Ever001). Travere will lead development and commercialization outside Greater China and select APAC markets, leveraging its strong nephrology expertise and existing commercial infrastructure. Everest retains rights in Greater China.
• Siviributinib Clinical Data: In Primary Membranous Nephropathy (PMN), Ever001 demonstrated rapid reduction in anti-PLA2R autoantibodies (~80% at high dose) followed by substantial proteinuria reduction (~80% by week 36). The drug is a selective, reversible covalent BTK inhibitor, showing a differentiated safety profile without typical platelet, neutropenia, cardiac, or liver signals seen in earlier-generation BTK inhibitors.
• Pipeline Expansion: Based on PMN proof-of-concept, Everest is initiating basket studies in FSGS, Minimal Change Disease (MCD), and IgA Nephropathy in China. The long-term vision includes expanding into other immune-mediated kidney diseases and potentially broader autoimmune conditions.
• mRNA Cancer Vaccines: Two platforms are active: Tumor-Associated Antigen (TAA) vaccines (e.g., EVM-14 for squamous cell carcinoma) which are off-the-shelf and lower cost; and Personalized Cancer Vaccines (PCV) like EVM-16. EVM-16 showed compelling immunogenicity in an IIT study for solid tumors, with a Phase 1B IIT planned for H2 2024 in first-line NSCLC maintenance setting, aiming for data readout in 2027.
• In Vivo CAR-T Platform: Everest is developing an in vivo CAR-T approach using antibody-conjugated LNPs to deliver mRNA coding for CARs into T cells. Current focus is on CD19 CAR-T. Key advantages include scalability, lack of need for lymphodepletion, and cell-free manufacturing. Transfection efficiency in non-human primates ranges from 40-80%, with 40% already yielding compelling B-cell depletion. Major hurdles remaining are durability, safety, and the ability to re-dose.
• Regulatory Milestones: US IND filing for the in vivo CAR-T program is targeted before the end of 2024.

• In Vivo CAR-T US IND: Management reaffirms guidance to file the Investigational New Drug (IND) application in the US before the end of 2024.
• EVM-16 PCV Study: Launch preparation for the Phase 1B IIT study (first-line NSCLC maintenance) is underway, with initiation expected in the second half of 2024.
• Data Readouts: Expectations for meaningful validation of the PCV platform are set for 2027 regarding the EVM-16 NSCLC study. Answers regarding durability and re-dosing capabilities for in vivo CAR-T are anticipated within the next 6-12 months based on ongoing IIT studies.

No financial segment performance data or revenue contribution percentages were provided in this transcript. The discussion focuses on clinical development, partnership strategy, and pipeline updates rather than financial results.

• Clinical Uncertainty: Early-stage data for Siviributinib in new indications (FSGS, MCD, IgAN) and cancer vaccines requires further validation to confirm efficacy and mechanistic hypotheses.
• Technical Challenges: For in vivo CAR-T, key technical hurdles include ensuring durable B-cell depletion, safe re-dosing capabilities, and optimizing transfection efficiency/duration. Long-term safety and expression duration remain unknown.
• Development Pace: Progress across multiple indications and programs depends heavily on data generation and regulatory interactions, which may vary in speed.

Q: Why was Travere Therapeutics selected as the partner for Siviributinib, and how will development responsibilities be divided?

A: Ian Wu highlighted Travere’s deep expertise in nephrology, noting their team size focused solely on nephrology rivals large pharma FTEs. Their successful track record with sparsentan for FSGS and IgA nephropathy instilled confidence in their ability to maximize value. Under the agreement, Travere leads development and commercialization outside Greater China and select APAC markets, while Everest manages these regions. Joint governance structures ensure coordinated global strategy, with PMN as the lead indication and future indications guided by data and regulatory feedback.

Q: How does Siviributinib’s mechanism differentiate it from other BTK inhibitors, and what is the basis for expanding into other renal diseases?

A: Wu explained that Siviributinib is a selective, reversible covalent BTK binder, offering potent binding without the platelet, cardiac, or liver safety signals associated with earlier irreversible BTK inhibitors. This profile supports chronic use. In PMN, it rapidly reduced autoantibodies (approx. 80%) followed by significant proteinuria reduction (approx. 80%). This sequence validates BTK inhibition as a relevant target in immune-mediated glomerular diseases, prompting basket studies in FSGS, MCD, and IgA nephropathy to test the broader hypothesis that dysregulated immune signaling drives podocyte injury across these conditions.

Q: What is the strategic distinction between Everest’s TAA and PCV mRNA vaccine programs, and what are the near-term milestones?

A: Wu distinguished TAA vaccines (like EVM-14) as off-the-shelf, lower-cost biologics targeting specific tumor types (e.g., squamous cell carcinoma), suitable for broader patient populations including earlier stages. In contrast, PCVs (like EVM-16) are personalized. EVM-16 showed compelling immunogenicity in a prior IIT study for solid tumors. A Phase 1B IIT for first-line NSCLC maintenance in combination with PD-1 inhibitors will launch in H2 2024, with data expected in 2027. This early-line setting balances faster data readout with potential for greater commercial impact compared to adjuvant settings.

Q: What are the technical advantages and current challenges of Everest’s in vivo CAR-T platform?

A: The in vivo CAR-T approach uses antibody-conjugated LNPs to deliver CAR mRNA directly into T cells, aiming for an off-the-shelf, scalable, cell-free therapy that avoids lymphodepletion. Initial programs target CD19. While cell specificity and transfection efficiency (40-80% in NHPs, with 40% showing efficacy) are manageable, the primary hurdles are durability, safety, and the ability to re-dose patients if diseased B-cells return. Everest aims to resolve these questions over the next 6-12 months via ongoing IIT studies and plans to file a US IND before year-end 2024.