Zymeworks Inc. Q2 FY2024 earnings call

• Development milestones: Zanidatamab received priority review for BLA in US for second-line BTC with target action date Nov 29, 2024; EMA validated marketing authorization application for zanidatamab in second-line BTC; BeiGene received $8M milestone payment; ZW171 and ZW191 cleared IND by FDA with first-in-human studies planned in H2 2024; discontinued clinical development of zanidatamab zovodotin.
• Financial results: Net loss for six months ended June 30, 2024 was $69.3M vs $75.5M in 2023; revenue $29.3M vs $42.6M in 2023; operating expenses decreased 11% year-over-year; cash resources as of June 30, 2024 were $395.9M.
• Pipeline updates: ZW171 and ZW191 advanced to clinical stage; focus on ADCs and multi-specific antibodies; ZW220 and ZW251 on track for IND filings in 2025.

No detailed segment performance by product with revenue contribution percentages was provided in the transcript. Financials were discussed generally, but no specific product segments with clear revenue breakdown and contribution % as required.

• Jazz expects top-line PFS data for zanidatamab in first-line GEA in Q2 2025; Jazz aiming to launch zanidatamab in US for second-line BTC in Q4 2024; FDUFA date for zanidatamab in US is Nov 29, 2024; board authorized $60M share repurchase program with $30M to begin in H2 2024.

• Uncertainties in regulatory reviews for zanidatamab in different regions; potential clinical trial challenges for ZW171 and ZW191; impact of soluble mesothelin on ZW171's efficacy; risks associated with T cell engager development like T cell exhaustion or CRS in mesothelin negative patients.

Q: Speak to levels of testing and folate receptor alpha expression for Phase 1, IHC cut-off values, starting dose, step-up dosing, inpatient administration?

A: Pranshul Chauhan stated that expression levels will be analyzed prospectively initially, starting dose not publicly shared, there will be inpatient requirements in a small subset during dose escalation due to regulatory requirements.

Q: Jazz pushing back Horizon G801 data, enrollment progress, PFS events?

A: Ken Galbraith said enrollment is on track, delay in unblinded study due to required events for unblinding, no disclosure of actual PFS events.

Q: Side effect profile of ZW171, preclinical insights, number of doses in Phase 1?

A: Paul Moore discussed preclinical characterization showing limited toxicity on normal tissue levels of mesothelin, Pranshul Chauhan mentioned evaluating six dose levels with 21-day DLT evaluation period.

Q: Mesothelin negative patients, CRS, T cell exhaustion, soluble mesothelin impact on ZW171?

A: Paul Moore addressed that most tumor types have some mesothelin expression, T cell activation mechanism minimizes negative effects, and soluble mesothelin has minimal impact on ZW171's killing activity.

Q: Folate receptor alpha program, payload benefit of higher antibody dose?

A: Paul Moore explained that higher antibody dose allows better drug targeting to tumor, increasing the chance of drug reaching the tumor site.

Q: Share repurchase program, use of capital vs clinical development?

A: Ken Galbraith said capital was reallocated from Zani-Zo for share repurchase, current R&D programs are well funded and share repurchase is a thoughtful capital allocation to boost shareholder return.

Q: Go/no-go signal in dose escalation for ZW171, reference point for ovarian cancer and NSCLC?

A: Pranshul Chauhan stated focus on safety and tolerability in Phase 1 study, gathering efficacy data using RECIST criteria for ovarian cancer and NSCLC.