EVEX

This fireside chat webcast focused on Everest Medicines' strategy, recent partnership with Travere Therapeutics, and pipeline progress. Key points are organized below:

• Sivore Brutinib (Ever001) Partnership with Travere Therapeutics
  • The partnership is structured with a strong strategic fit: Travere is a recognized leader in rare kidney disease, with fully dedicated nephrology-focused clinical development, regulatory, and commercial capabilities matching the profile of large pharma nephrology teams. Travere has a proven track record of FDA approval for sparsantan (filspari), the first approved treatment for FSGS and the second approved for IgA nephropathy, giving Everest confidence in their ability to advance the asset.
  • Development division: Travere will lead global development and commercialization for territories outside of Greater China and select APAC markets, while Everest retains responsibility for its home territories. The two firms have established joint governance structures to coordinate global development and decision-making, leveraging each party's strengths.
  • Indication strategy: Primary membranous nephropathy (PMN) is the lead indication, with existing compelling proof-of-concept data. Additional priority indications include immune-mediated FSGS, minimal change disease (MCD), and other renal indications, with development pace and sequence guided by clinical data, scientific rationale, and regulatory input.
  • Mechanism and differentiation: Sivore Brutinib is a selective reversible covalent BTK inhibitor. In PMN trials, it produced rapid, substantial reductions in anti-PLA2R autoantibodies, followed by meaningful reduction in proteinuria, improved serum albumin, and stabilized kidney function, with an 80% proteinuria decline by week 36. It does not show the platelet, neutropenia, cardiac, or liver safety signals common to earlier generation BTK inhibitors, giving it a differentiated profile suitable for chronic use in autoimmune diseases.
• mRNA Platform and Cancer Vaccine Pipeline
  • Everest has two mRNA cancer vaccines in clinical development, with a third preclinical immunomodulatory vaccine in the works, advancing from its proprietary AI-enabled mRNA discovery platform. It is also actively pursuing business development opportunities to repeat the success of its Ever001 licensing and development model.
  • Tumor-associated antigen (TAA) vaccines are off-the-shelf products targeting specific tumor types, suitable for broad patient populations across disease stages, with low manufacturing cost. The lead TAA candidate EVM-14 targets five antigens for squamous cell carcinomas and is advancing in clinical development.
  • Personalized cancer vaccines (PCV) have more existing clinical validation; Everest's lead PCV candidate EVM-16 completed a Phase 1 investigator-initiated trial (IIT) in solid tumors, with compelling immunogenicity and early efficacy signals disclosed at AACR 2024. A Phase 1b IIT in first-line non-small cell lung cancer maintenance in combination with PD-1 inhibitors will initiate in H2 2024, with data expected in 2027.
• In Vivo CAR-T Pipeline
  • Everest's approach uses antibody-conjugated LNPs to deliver mRNA coding for CAR constructs, targeting a broad subset of T cells. The goal is to convert autologous personalized CAR-T therapy into an off-the-shelf, cell-free, scalable product that does not require pre-treatment lymphodepletion.
  • Everest has proprietary LNP libraries, with a lead candidate that preferentially targets the spleen over the liver, plus mRNA sequence modifications to reduce off-target liver expression. Non-human primate studies achieved 40% to 80% T cell transfection efficiency, with 40% transfection already producing robust B-cell depletion.

• The Phase 1b IIT for EVM-16 (personalized cancer vaccine) will initiate in the second half of 2024, with data readout expected in 2027.
• Everest expects to file a US IND for its lead in vivo CAR-T program before the end of 2024, with initial data from ongoing China IIT studies expected in the next 6 to 12 months.
• No upward or downward revision of prior financial guidance was provided in this webcast.

No financial segment performance data or numerical revenue/earnings figures were provided in this webcast transcript.

• Sivore Brutinib is still in early clinical development, and while no major safety signals typical of earlier-generation BTK inhibitors have been observed to date, full long-term safety profiling is still ongoing.
• The broader indication expansion hypothesis for BTK inhibition across multiple immune-mediated kidney diseases (beyond PMN) is still being tested in clinical trials, and success is not guaranteed.
• The in vivo CAR-T field faces unresolved key industry challenges: achieving complete, durable safe B-cell depletion, and enabling effective redosing if diseased B cells return. These technical hurdles have not yet been definitively solved for the field as a whole, including Everest's program.
• All pipeline assets (cancer vaccines, in vivo CAR-T) are in early stages of development, and clinical proof of concept for safety and efficacy is still pending for multiple candidates.

Q: What made Travere the right partner for Sivore Brutinib, and how are responsibilities divided between the two companies? / A: Travere is an ideal fit because it is a dedicated leader in rare kidney disease with proven experience gaining FDA approval for nephrology assets, matching Everest's own view of Sivore Brutinib as a broad pipeline for multiple immune-mediated kidney diseases. Travere leads development and commercialization outside of Greater China and select APAC, while Everest leads in its home territories. The two firms use joint governance to coordinate global development, with PMN as the lead indication and other renal indications prioritized based on future data.

Q: How confident are you that PMN proof of concept will translate to other renal indications, and what differentiates Sivore Brutinib from existing approaches? / A: The mechanism of BTK inhibition targeting dysregulated immune signaling driving podocyte injury applies across PMN, FSGS, MCD and IgA nephropathy, so PMN data provides strong confidence for broader testing. Sivore Brutinib's reversible covalent BTK binding gives it a better safety profile than earlier BTK inhibitors, with no common off-target signals observed to date, making it suitable for chronic use, creating a differentiated profile for autoimmune renal disease.

Q: What are the roles of personalized vs. off-the-shelf mRNA cancer vaccines, and when will we get next meaningful platform validation data? / A: Off-the-shelf TAA vaccines target specific tumor types, are accessible for broad patient populations across all stages, and have low cost, while personalized cancer vaccines already have more existing clinical validation. Next key data will come from the EVM-16 Phase 1b IIT starting in H2 2024, with readout in 2027, testing the PCV in first-line NSCLC maintenance in combination with PD-1 inhibitors.

Q: What is the key technical advantage of Everest's in vivo CAR-T approach, and what is the biggest hurdle to solve? / A: Everest's approach enables an off-the-shelf, scalable, cell-free in vivo CAR-T product that eliminates the need for lymphodepletion, a major improvement over conventional autologous CAR-T. The biggest industry-wide hurdle that remains to be solved is achieving complete, durable safe B-cell depletion and enabling effective redosing when needed. Everest expects initial answers to these questions from ongoing China IITs in the next 6-12 months, with a US IND filing planned by end-2024.

Q: How has global pharma's evaluation of China-originated innovation changed in recent years? / A: Global pharma has dramatically increased its local presence in China, with dedicated sourcing and evaluation teams across therapeutic areas, and a much stronger commitment to engaging with the local innovation ecosystem. Beyond that, the core evaluation criteria have not changed: global partners still prioritize genuine differentiation, strong intellectual property, solid CMC/manufacturability, credible translational data, and trust and alignment with the partner management team.