AAPG

Pipeline and Clinical Progress

• Enrollment for the Polaris 1 trial of olverembatinib is on track, with plans to file two NDAs with the FDA in the second half of next year, based on 3-month MRD-negative complete response rate endpoints.
• One BCL-2 inhibitor (lisaftaclax) is already approved and commercially launched in China, with commercial expansion ongoing.
• The APG-3288 (BTK degrader) Phase 1 dose-escalation trial is ongoing across the US and China, with IND filings in progress for non-oncology/autoimmune indications including multiple sclerosis, requiring placebo-controlled trial design.
• The EED inhibitor APG-5918 Phase 1 trial in relapsed/refractory settings has enrolled nearly 100 patients, and data will be presented at the 2024 ASH meeting.
• The MDM2-p53 inhibitor APG-115 has shown promising clinical benefit in combination with a BCL-2 inhibitor for pediatric soft tissue tumors, a field with no currently approved MDM2-p53 inhibitors.

Commercial Progress in China

• The company is on track to hit the previously stated target of accessing 2,000 hospitals in China, with the goal of covering 80% of the target market for the company's two approved products.
• The current Chinese commercial team has ~300 members, with plans to expand to ~400 total members.

Partnership Status

• The company holds a global exclusive partnership option agreement with Takeda for olverembatinib, with total potential aggregate payments of $1.2 billion plus tiered royalties ranging from 12% to 19%. The company and Takeda are collaborating closely on trial enrollment, KOL engagement, and commercial planning ahead of any option exercise.

Financial Position

• Current cash on hand is sufficient to support the full R&D plan through the end of 2027, with spending adhering to forecasts. Operating expenses are now at peak levels as most late-stage registration trial enrollment is more than 50% complete.

• The company expects to complete enrollment for the Glora 4 trial by the end of 2024 or early 2025, with NDA submission possible after enrollment completion using CR rate as the primary endpoint, while overall survival data continues to mature.
• Two NDAs with the FDA are targeted for submission in the second half of 2025, and Polaris 1 trial enrollment remains on track to meet this timeline.
• Operating expenses have reached their peak as of the current quarter, with spending aligned to plan for remaining late-stage enrollment and upcoming NDA filings.
• The 2,000-hospital access target in China remains on track to be achieved as planned.

No segment-level financial performance data or revenue contribution percentages were provided in the transcript. No financial figures for product segments were shared.

• The FDA requires randomized controlled trials (RCTs) for registration under Project Optimus, rather than single-arm trials, increasing trial cost, complexity, and timelines for the company's lead assets.
• The CML market has entrenched existing competition, and the company must demonstrate clear differentiation in efficacy and safety to gain market share.
• Multiple pipeline assets are still in early clinical stages, with no guarantee of successful clinical trial outcomes or regulatory approval.
• Developing global registration trials across multiple geographies requires significant capital expenditure, even with existing cash reserves, and the company may need additional fundraising to support full commercialization.

Q: When will Takeda decide on its global license option for olverembatinib, is the 2,000-hospital China access target on track, and will APG-3288 Phase 1 data be presented at this year's ASH, with plans for MS development?

A: APG-3288's Phase 1 dose escalation missed the ASH abstract cutoff, so no data will be presented this year; data is now expected to be shared at IHA 2025. INDs for autoimmune indications including MS are expected to be filed soon, though data collection will be slightly delayed due to required placebo controls. The 2,000-hospital target remains on track with the commercial team expanding from 300 to 400 staff to cover 80% of market potential. The company is working closely with Takeda on trial and commercial planning ahead of their decision, which is tied to patent expiration of the legacy CML drug early next year, with a $1.2B total payout plus 12-19% tiered royalties if the option is exercised.

Q: What differentiates olverembatinib from competing CML therapies, and what should be expected for upcoming Polaris and Glora trial readouts?

A: Olverembatinib is the most potent therapy against a broad spectrum of CML mutations, including the T315I gatekeeper mutation and compound mutations that occur in ~40% of late-line patients. Competitor products either require 5x higher dosing (leading to 5x higher costs near $1 million USD) or lack strong clinical data on compound mutations. Olverembatinib is the only competitor that has an FDA-aligned registration RCT with a bosutinib control arm, and it is positioned for early use after first-line failure to help patients achieve deeper responses that enable treatment-free remission.

Q: How does lisaftaclax differentiate from competing BCL-2 inhibitors including the newly launched pirtobrutinib, and what is the real-world benefit of its 5-day ramp-up schedule?

A: Lisaftaclax has a shorter half-life that translates to a better safety profile, with less neutropenia, thrombocytopenia, and lower infection risk compared to existing competitors. It also has a lower risk of drug-drug interactions, which is critical for combination therapies with azacitidine for high-risk MDS and co-administration of antifungals for myeloma patients. Unlike competitors that require weekly dosing, hospitalization, and close monitoring for tumor lysis syndrome, lisaftaclax's 5-day ramp-up is far more convenient for chronic daily dosing.

Q: How is the company prioritizing pipeline resources beyond its two commercial assets, and what is the outlook for OPEX and cash over the next 12 months?

A: The company prioritizes pipeline programs in a data-driven manner. The most exciting late-stage pipeline programs are the MDM2-p53 inhibitor APG-115, EED inhibitor APG-5918 (data coming at ASH 2024), and BTK degrader APG-3288, all of which have leading global positions. Current cash is sufficient to support all planned activities through 2027, and OpEx has now reached its peak as most enrollment for late-stage trials is already complete. The company is positioned to complete all remaining enrollment and upcoming NDA filings with existing cash reserves.