Daina Graybosch

Daina Graybosch asked for an update on Merck's biomarker strategy for sac-TMT, particularly in light of a competitor's recent decision to narrow Phase III primary endpoints to Trop-2 expressers, and whether this strategy would be evident in any of Merck's ongoing Phase III trials.

Answer

Dean Li, President of Research Laboratories, Merck & Co. Inc, reiterated that sac-TMT has the potential to be best-in-class and emphasized the importance of placing it in the right tumor types with the correct strategy. He explained that a biomarker might not be needed in all tumor types but would be crucial in others, especially when facing strong comparators, making the strategy context-dependent.

Daina Graybosch asked for an update on Merck's biomarker strategy for sac-TMT, particularly in light of a competitor's recent decision to narrow primary endpoints in Phase 3 trials to focus on Trop-2 expressers.

Answer

Dean Li, President of Research Labs, reiterated that sac-TMT has best-in-class potential and that the biomarker strategy is context-dependent. He explained that for some tumor types, a biomarker may not be needed, while for others, it will be crucial, especially when facing strong comparators, emphasizing that the decision is based on the specific tumor and existing treatments.

Daina Graybosch of Leerink Partners inquired about the Phase 2 CADENCE trial for Winrevir, asking about the clinical bar for success for its primary outcomes and whether a Phase 3 trial would require hard cardiovascular outcomes for registration.

Answer

Dr. Dean Li, President of Merck Research Labs, responded that the most important signal from the trial would be a substantial impact on pulmonary vascular resistance (PVR). He also stated his expectation that the FDA would likely require a Phase 3 trial to demonstrate effectiveness in this broader patient population.

Daina Graybosch of Leerink Partners asked about the upcoming Phase 2 CADENCE trial for Winrevir, seeking clarity on the clinical bar for success for its primary endpoints and whether a future Phase 3 trial would need to show hard cardiovascular outcomes for registration in the HFpEF indication.

Answer

Dr. Dean Li, President of Merck Research Laboratories, responded that the trial focuses on a heart failure population with PAH-like physiology. He emphasized that the most critical signal would be a substantial impact on PVR (pulmonary vascular resistance). Dr. Li stated his expectation, pending data, is that the FDA would likely require a Phase 3 trial to demonstrate effectiveness in this broader patient group.

Daina Graybosch inquired about the early-stopped HYPERION trial for WINREVAIR, asking what outcomes data could be provided and whether it would be sufficient to support use in less severe patients, where toxicity concerns might be higher.

Answer

Dr. Dean Li, President of Merck Research Labs, emphasized the goal of building an 'evidentiary wall' for WINREVAIR. He highlighted that the ZENITH trial data on hard outcomes would be presented at ACC '25. For HYPERION, he explained it was stopped early due to a loss of clinical equipoise, but the study remains blinded, so data will be shared later. He also noted that the long-term safety experience remains well within the product's label.

Daina Graybosch of Leerink Partners questioned the pneumococcal vaccine opportunity, asking about the incremental market size from the CAPVAXIVE label expansion to age 50 and what to look for in the upcoming MMWR publication.

Answer

Dr. Dean Li emphasized CAPVAXIVE's superior profile, with its 21-valent formula providing 85% adult protection versus a competitor's 54%, which he believes drove the ACIP's recommendation. CFO Caroline Litchfield quantified the expanded opportunity, noting the 50-64 age group adds 60 million people to the addressable market in the United States, bringing the total over-50 population to 120 million.

Daina Graybosch asked about Compugen's expectations for the upcoming Arcus-Gilead TIGIT readout in gastric cancer, and whether any outcomes from that trial could diminish confidence in Compugen's own FC-reduced TIGIT (COM902) or the bispecific rilvegostomig.

Answer

President and CEO Eran Ophir stated that a successful readout would validate the FC-reduced TIGIT hypothesis, highlighting its potential advantages over FC-active formats. He added that even if the Arcus-Gilead trial fails, AstraZeneca's bispecific rilvegostomig has additional advantages, including enhanced activity and a potentially easier regulatory path due to its bispecific format.

Daina Graybosch inquired about the upcoming Arcus-Gilead TIGIT readout in gastric cancer, asking what Compugen is looking for and if any outcomes could reduce confidence in their own TIGIT programs or the bispecific rilvegostomig.

Answer

Eran Ophir, President and CEO of Compugen, stated that a successful readout would validate the FC-reduced TIGIT hypothesis. He added that even if the Arcus trial fails, AstraZeneca's bispecific Rilva has advantages, including potential for enhanced activity through cooperative binding and an easier regulatory path in some trials due to its bispecific nature, not requiring contribution of components.

Daina Graybosch asked for details on the COM701 ovarian cancer trial design, including its statistical power, methods for ensuring patient balance, the rationale for its initial size, and how eligibility criteria might bias the patient population.

Answer

Chief Medical Officer Dr. Michelle Mahler clarified it is an exploratory adaptive trial using Bayesian statistics to assess the probability of a 3-month PFS improvement, not powered as a pivotal study. President and CEO Dr. Anat Cohen-Dayag added the design allows for expansion. Dr. Mahler noted balance is achieved via stratification for prior PARP inhibitor use, a key biological factor.

Daina Graybosch of Leerink Partners asked about the key learnings from previous trials of PD-1/PD-L1 antagonists in ovarian cancer and whether any studies were conducted in the specific platinum-sensitive maintenance setting that Compugen is now targeting.

Answer

Guest investigator Dr. Oladapo Yeku explained that prior PD-1 trials showed low overall response rates (~10-14%) but some durable responses, with better outcomes in earlier lines of therapy. He confirmed no major trials have been done in this exact maintenance setting. Chief Scientific Officer Dr. Eran Ophir differentiated COM701, noting its unique PVRIG blockade mechanism has the potential to drive T-cell activity even in PD-L1 negative patients, unlike PD-1 inhibitors, making it well-suited for this setting.

Daina Graybosch asked about BioNTech's overall strategy for pumitamig, specifically the 'establish and elevate' approach, and questioned why the company isn't pursuing simultaneous multi-arm Phase III studies with ADC combinations and pumitamig on top of traditional standard of care, especially in competitive indications.

Answer

Özlem Türeci, Chief Medical Officer and Co-founder, clarified that the three-wave strategy (establish, expand, elevate) involves parallel activities. She noted a focus on chemo combinations for faster initiation and speed to market, while data generation for ADC combination studies is ongoing and will follow the 'establish' wave soon.

Daina Graybosch questioned BioNTech's 'establish and elevate' strategy for pomitamic, asking why the company isn't pursuing simultaneous development with ADC combinations in multi-arm Phase 3 studies to leapfrog competition, especially given early ADC data and fierce market dynamics.

Answer

Özlem Türeci, Chief Medical Officer and Co-founder, clarified that the three-wave strategy (establish, expand, elevate) involves parallel activities. She emphasized focusing on chemo combinations for speed to market, while acknowledging that data generation for ADC combinations is ongoing and will follow the initial 'establish' wave.

Daina Graybosch asked about the strategy for BNT327 in frontline triple-negative breast cancer (TNBC), particularly in light of the success of TROP2 ADCs, and whether a trial could proceed without a TROP2 ADC in the active or control arm.

Answer

CEO Ugur Sahin explained that TNBC presents several opportunities for BNT327, citing encouraging PFS and OS data from combinations with chemotherapy. He noted that combining with ADCs, such as their TROP2 or HER3 candidates, could further enhance efficacy and confirmed a combination study is currently underway.

Daina Graybosch asked about the anticipated outcome of the CDC's ACIP vote on COVID-19 boosters and the potential sales impact if the U.S. recommendation is narrowed to a risk-based approach.

Answer

Chief Strategy Officer Ryan Richardson noted that the majority of U.S. vaccinations already target the 65+ and immunocompromised groups, so their base scenario of around 20% vaccination rates remains intact. CFO Jens Holstein added that similar risk-based policies exist in other regions and that the final impact is hard to predict as some individuals get vaccinated regardless of official recommendations.

Daina Graybosch of Leerink Partners inquired about the timeline for significant legal IP cases and the context for upcoming FixVac data in melanoma, given the iNeST trial results in a similar setting.

Answer

CFO Jens Holstein and CSO Ryan Richardson expressed confidence in their IP portfolio, directing investors to the 20-F filing for details on legal disputes. Regarding the vaccine data, CMO Özlem Türeci and CEO Ugur Sahin explained that the off-the-shelf FixVac can be administered immediately, a critical advantage in rapidly progressing metastatic melanoma compared to the personalized iNeST vaccine. They reiterated their strategy of focusing iNeST on the adjuvant setting where there is more time for an immune response to develop.

Daina Graybosch asked about the VEGF PD-L1 bispecific, BNT327, noting its similar outcomes to a competitor's PD-1 bispecific and questioning if this was expected, what it implies about the mechanism, and where BNT327 could be differentiated.

Answer

CEO Dr. Ugur Sahin explained that while both bispecifics neutralize VEGF and PD-1/PD-L1 interaction, BNT327 targets PD-L1, which could potentially enrich it in the tumor microenvironment. He acknowledged that data in overlapping trials looks similar but suggested it's too early to validate if the mechanistic difference translates to better response rates, particularly in PD-L1 positive tumors, though a slight trend exists.

Daina Graybosch from Leerink Partners inquired about the implications of Innate Pharma's strategic shift away from ANKET® assets and the departure of Chief Scientific Officer Eric Vivier, specifically regarding the future potential of targeting NK cells.

Answer

Jonathan Dickinson, CEO & Director, clarified that Eric Vivier will continue to advise the R&D committee and that NK cell research is ongoing through an extended collaboration. He emphasized that while NK cells are no longer a main priority, future decisions on NK cell engagers will be driven by clinical data and market relevance, with IPH6501 studies continuing and IPH6101 explored via investigator-initiated research.

Daina Graybosch inquired about the specific efficacy and safety criteria Innate Pharma will use to determine if further internal investment in the IPH6101 (CD123 ANKET) program is warranted once the data is returned from Sanofi.

Answer

Yannis Morel, Chief Operating Officer, stated it was too early to define a specific bar as the full data package had not yet been transferred. Jonathan Dickinson, CEO, added that the criteria would depend heavily on the data itself, which will determine the optimal clinical setting for the asset—be it for refractory, first-line, or maintenance AML—each of which would have different investment thresholds.

Daina Graybosch inquired about Innate's strategy for defining a biomarker threshold for Lacutamab in Mycosis Fungoides (MF) and asked about the potential for developing the IPH-6501 NK cell engager for autoimmune diseases.

Answer

Chief Medical Officer Sonia Quaratino explained that the TELLOMAK trial was designed with cohorts expressing KIR3DL2 above and below a 1% threshold to inform the biomarker strategy, with interesting data expected in both groups. Chief Operating Officer Yannis Morel and Interim CEO Hervé Brailly added that while using the ANKET platform for autoimmune diseases is a potential long-term option, the immediate focus is on establishing safety and dose for IPH-6501 in oncology.

The analyst asked detailed questions about the ANKET platform, focusing on the potential for a bell-shaped dose-response curve, learnings from the CD123 program, and how these learnings about dose optimization and affinity are being applied to newer programs like the CD20 ANKET (ANKET 4 vs. ANKET 3).

Answer

The company acknowledged that a bell-shaped dose curve is a known phenomenon that they model and address during lead optimization by selecting binders with appropriate properties. For the newer ANKET 4 platform (used for the CD20 program), its increased potency at low receptor occupancy may mitigate this issue compared to the ANKET 3 platform, though clinical data will be required for confirmation.

Daina Graybosch asked about the TIGIT program, questioning if Arcus is underinvesting relative to AstraZeneca, and inquired about the efficacy bar for casdatifan monotherapy to potentially compete with TKIs in a head-to-head trial.

Answer

President Juan Jaen defended their TIGIT strategy, stating they feel good about their bets in large markets like lung and gastric cancer and have other opportunities teed up pending positive Phase III results. Regarding casdatifan, CEO Terry Rosen and President Juan Jaen explained that while early cohorts are exploratory, an ORR in line with the high-teens to 40% range of TKIs, combined with a better safety profile, would be very exciting for clinicians.

Daina Graybosch of Leerink Partners asked about Arcus's strategy for managing treatment exposure and toxicity in its upcoming combination trials, specifically PEAK-1 with cabozantinib and the trial with AstraZeneca's volrustomig.

Answer

CMO Dimitry Nuyten explained that for PEAK-1, the lack of overlapping toxicities between casdatifan and cabozantinib simplifies management. For the AstraZeneca trial, he noted that investigators are experienced with managing ipi-nivo-like toxicities, and the non-overlapping profiles will again make dose modification guidance straightforward.

Daina Graybosch of Leerink Partners requested details on the patient demographics and regional enrollment for the ARC-10 trial to help set expectations and facilitate comparisons with other anti-TIGIT studies.

Answer

CEO Terry Rosen framed the upcoming ARC-10 data as an important and positive dataset for the anti-TIGIT field. CMO Dimitry Nuyten clarified the trial enrolled about 40 patients each in the domvanalimab+zimberelimab and zimberelimab monotherapy arms, and 20 in a chemotherapy arm. He noted it was conducted ex-U.S. but is comparable to other first-line studies, with the chemo arm serving as a benchmark.

An analyst from Leerink Partners, on for Daina Graybosch, asked how Arcus's HIF-2 alpha inhibitor, casdatifan, is differentiated from Novartis's molecule and if Novartis's decision to discontinue its program has any read-through. He also asked how recent data for etrumadenant might change its perceived opportunity relative to quemliclustat and if new trials for etrumadenant are planned.

Answer

President Juan Jaen stated that in-vitro evaluations suggest the Novartis molecule is about an order of magnitude weaker than casdatifan. CEO Terry Rosen added there is zero read-through from the discontinuation, emphasizing molecule quality. Regarding etrumadenant and quemliclustat, Rosen said both are viewed as having great potential and that combining them could be contemplated in the future. He confirmed they expect to do more with etrumadenant following the strong ARC-9 data, but plans are still being finalized with Gilead and the FDA. COO Jennifer Jarrett highlighted that ARC-9's acceptance as an oral presentation at ASCO signals its significance.

Daina Graybosch inquired about the process and timeline for adding lenacapavir to the USPSTF mandate for coverage without cost-sharing and the potential revenue uplift from such a designation.

Answer

Chief Commercial Officer Johanna Mercier explained that while they will pursue the USPSTF update, their launch plans for the first 6-12 months do not assume it will be in place. She expressed confidence that the transformative nature of lenacapavir will drive access through standard channels, similar to past launches. The mandate is viewed as a 'nice to have' that would provide a future tailwind rather than a prerequisite for initial success.

Daina Graybosch asked new Chief Medical Officer Dietmar Berger for his perspective on the competitiveness of Gilead's late-stage oncology portfolio, specifically focusing on Trodelvy and the TIGIT inhibitor domvanelumab.

Answer

CMO Dietmar Berger expressed confidence in the portfolio. He highlighted Trodelvy's upcoming Phase III readouts and its unique overall survival benefit in key cancers. For TIGIT, he noted its potential for differentiation due to its Fc-silent design but stressed that the ongoing Phase III trials will ultimately define its path forward.

Daina Graybosch of Leerink Partners inquired about the gating factors for the anito-cel regulatory filing and what will be required to expand the CAR-T market in multiple myeloma beyond the current low penetration rates.

Answer

An executive, likely EVP of Kite Cindy Perettie, explained that while the FDA typically requires 12 months of data for filing, Gilead plans to discuss the review timeline with the agency based on anito-cel's differentiated safety profile. To grow the market, she noted that the ongoing work to overcome reimbursement and access challenges in community practices for lymphoma will be directly applicable to expanding anito-cel adoption in multiple myeloma.

Inquired about the company's expanded partnership strategy and the potential future development path for the AFM24 program, including possible combination therapies.

Answer

The company explained their broadened partnership strategy now includes a wider range of options like regional deals, not just large multinational partners, to secure non-dilutive capital. For AFM24, they are awaiting mature PFS data before deciding on a path forward, which could involve a randomized trial of the current doublet or exploring triplet combinations with agents like VEGF inhibitors or docetaxel.

Inquired about the overall development strategy across the three main programs, focusing on the evolving plan for AFM28 combinations and the potential for a single-agent path based on a durability threshold.

Answer

The company explained that the strong 50% CR/CRi monotherapy data for AFM28 has broadened its strategic options beyond just NK cell combinations to include other partners or a potential monotherapy path. A durability of around 6 months PFS would be considered meaningful for a single-agent AML therapy. For all programs, decisions are data-driven and all strategic options are being evaluated.

Asked for details on the types of patients and sites starting apheresis in the third line, and later followed up on the specifics of ABECMA's differential safety profile compared to competing products, particularly which neurotoxicities are most meaningful to physicians.

Answer

The company stated it's a mix of third-line and later-line patients, with major academic centers driving volume and some previous sites returning. The key safety differentiator is the very low frequency of delayed, non-ECA neurotoxicities like Parkinsonism, which is a significant factor for physicians. All patient subgroups have shown benefit.

Asked about the competitive landscape, specifically T-cell engagers, plans for a next-gen BCMA program using ADR technology, and a comparison of bendamustine-only vs. cyclophosphamide-only conditioning.

Answer

The company acknowledges competition from CD19 engagers and is developing products to compete on safety, convenience, and accessibility. They confirmed future product candidates will incorporate ADR technology to move beyond intense conditioning. Regarding conditioning agents, they noted bendamustine and cyclophosphamide are in the same class and data supports bendamustine as an effective alternative, giving them confidence in a cyclophosphamide-only regimen for FT819.

Speaking for Daina Graybosch of Leerink Partners, an analyst asked for Fate's view on competition from T-cell engagers in autoimmune disease and inquired if the next-generation BCMA program would utilize ADR technology and what advantages it would offer over CD19 programs.

Answer

CEO Scott Wolchko acknowledged the potential of CD19 engagers and stated Fate is developing its products to compete directly by focusing on superior safety, convenience, and moving away from harsh conditioning. He confirmed that future product candidates will incorporate ADR technology, as moving beyond intense chemotherapy is a core strategic goal for the company.

Inquired about the specific challenges in starting the lupus clinical trial over the past six months, the expected pace of enrollment, and when a substantial patient cohort's data might be available.

Answer

The main challenge is that physicians treating autoimmune diseases are unfamiliar with cell therapies. Fate's existing relationships with oncology centers are helping bridge this gap. Enrollment will be paced by FDA-mandated patient staggers (e.g., 28 days), so building a large cohort will take time. An initial update on the FT819 study is planned for this year, but the company urged patience.

Daina Graybosch from SVB Leerink inquired about the specific criteria defining a "profile supportive of further development" for inupadenant combinations and asked for an update on the expansion decisions for prostate cancer.

Answer

CMO Joe Lager clarified that a "supportive profile" for inupadenant combinations with pembrolizumab and chemotherapy indicates a safe dose, expected pharmacokinetics, and initial evidence of efficacy. He confirmed the company is expanding the pembrolizumab combination in melanoma but has decided against pursuing the combination in prostate cancer at this time to prioritize other development opportunities.

Daina Graybosch of SVB Leerink asked for iTeos's perspective on the broader TIGIT/CD226 axis following the GSK deal, their enthusiasm for various combinations including CD96, and their confidence in CD96 inhibition as the right approach.

Answer

President and CEO Michel Detheux stated the primary goal is the combination of their TIGIT antibody EOS-448 with GSK's PD-1, dostarlimab. He noted that combinations including CD96 could be explored in specific indications where GSK's data suggests potential synergy. Chief Medical Officer Joe Lager added that a PVRIG combination is also of interest but represents a later-stage opportunity.

Daina Graybosch of SVB Leerink asked for the rationale behind the current clinical development plan for the EOS-448 (anti-TIGIT) program, decision-making factors for the next six months, and whether the A2A/TIGIT combination is still being considered for pancreatic cancer. She also inquired about the uniqueness of the inupadenant biomarker compared to competitors' adenosine signatures.

Answer

Chief Medical Officer Dr. Joe Lager detailed the strategic rationale for prioritizing first-line non-small cell lung cancer and head and neck cancer for EOS-448 to gain a competitive edge. He confirmed continued interest in the A2A/TIGIT combination for pancreatic cancer. Regarding the biomarker, Dr. Lager explained that their unique, internally developed IHC assay for the A2A receptor itself, rather than a gene signature, appears to correlate with clinical outcomes, which may be a key differentiator.