Brian Cheng

Brian Cheng of JPMorgan Chase & Co. asked for more details on the growth of the BioReference business, specifically the 4Kscore diagnostic test, and whether its 6% growth was driven by the primary care setting. He also inquired about the additional studies for the Merck-partnered EBV vaccine and their timing to advance the program to Phase 2.

Answer

Adam Logal, SVP and CFO, clarified that 4Kscore growth is primarily from urology, with primary care efforts pending payer coverage, expecting high single-digit to low double-digit growth in 2026. Gary Nabel, CIO, explained that EBV vaccine studies focus on EBV-naive patients and reducing the age of inclusion, with data expected by year-end 2026 and Phase 2 starting in 2027.

Brian Cheng asked for more color on the growth in the BioReference business, specifically the 6% growth in the 4Kscore diagnostic test segment. He inquired if this growth was driven by momentum in the primary care setting and about the stability of this growth trajectory. He also asked about additional studies for the Merck partnership's Epstein-Barr virus vaccine and the timing for moving into Phase 2.

Answer

Adam Logal, SVP and CFO, OPKO Health, clarified that 4Kscore volume increases are from the urology field, as no meaningful primary care effort has begun due to ongoing payer coverage work. He expects high single-digit to low double-digit growth for 4Kscore in 2026, potentially accelerating with primary care penetration. Elias Zerhouni, Vice Chairman and President, OPKO Health, deferred to Gary Nabel, CIO, OPKO Health, who explained that ongoing studies aim to gather more data on EBV naive patients and reduce the age of inclusion to 12 years, positioning for Phase 2, which is expected to start next year.

Brian Cheng inquired if there's a need to refocus the existing sales force's goals this year, considering potential opportunities with increased sub-Q adoption. He also asked for insights into the expense projections and expected step-ups related to the direct-to-consumer (DTC) campaign, specifically the Next in MS program.

Answer

Adam Waldman, Chief Commercialization Officer, stated that TG Therapeutics employs a strategic expansion approach to its field force, adding personnel where opportunities arise. He expressed confidence in the current team and its pay-for-performance culture, indicating no need for a new goal. Regarding the DTC campaign, Mr. Waldman highlighted that the Next in MS partnership with Christina Applegate is building long-term category leadership, with incredibly positive feedback and engagement metrics (website visits, sign-ups, sessions) exceeding expectations.

Brian Cheng asked if there's a potential need to refocus the existing sales force goals this year, identifying any specific pocket opportunities, especially given increased sub-Q adoption. He also inquired about the expense projections related to the direct-to-consumer (DTC) campaign and the expected step-up.

Answer

Adam Waldman, Chief Commercialization Officer, stated that TG Therapeutics continues a strategic expansion approach to its field force, adding people where opportunities arise, and expressed confidence in the team's performance without needing a new goal. Regarding DTC, Mr. Waldman did not provide specific expense projections but highlighted that these efforts are aimed at building long-term category leadership. He noted that feedback from customers, patients, and advocacy groups has been incredibly positive, with engagement metrics like website visits and content interaction exceeding expectations.

Brian Cheng asked about specific downstream cytokines that would be most impacted, reliable, and easiest to monitor from an ex vivo stimulation test setting to best assess the pharmacodynamic (PD) of the IRF5 drug, given its 50%-80% reduction across TLR7, 8, and 9 pathways.

Answer

Jared Gollob, Chief Medical Officer, identified key cytokines and gene transcripts for monitoring. These include type 1 interferons (like interferon beta protein production and gene transcripts) and pro-inflammatory cytokines such as IL-12, tumor necrosis factor (TNF), and IL-6, which are stimulated by macrophages and dendritic cells. He noted that these can be measured at either the protein or gene transcript level as helpful biomarkers.

Brian Cheng asked about specific downstream cytokines that would be most impacted, reliable, and easiest to monitor in ex vivo stimulation tests for the IRF5 program, given its regulation across TLR7, 8, and 9 pathways.

Answer

CMO Jared Gollob identified key biomarkers for monitoring IRF5 degradation, including type 1 interferons (e.g., interferon beta protein and gene transcripts) and pro-inflammatory cytokines such as IL-12, tumor necrosis factor, and IL-6. He explained that these can be measured at both protein and gene transcript levels in ex vivo stimulation assays to assess the drug's pharmacodynamic effects across TLR pathways.

Brian Cheng asked about the frequency of the added supplementary liver blood tests in MAGNITUDE-2 after dosing, and if these additional tests would also be part of the trial modifications for the MAGNITUDE study.

Answer

President and CEO John Leonard clarified that additional blood draws were already implemented in MAGNITUDE-2 for recently dosed patients when the hold was initiated. He described the frequency as a couple of additional assessments in the weeks immediately after dosing, essentially weekly early on, then biweekly (or semiweekly) for weeks three, four, and five, ensuring good sampling during the highest risk period. He noted that ongoing clinical evaluations continue for all enrolled patients in MAGNITUDE.

Brian Cheng asked about the frequency of supplementary liver blood tests after dosing in the MAGNITUDE-2 trial and if similar added tests would be part of the MAGNITUDE trial modifications.

Answer

President and CEO John Leonard explained that additional blood draws were already introduced into MAGNITUDE-2 when the clinical hold was initiated, with trials continuing for enrolled patients. He described the new monitoring as a couple of additional assessments in the weeks immediately after dosing, specifically weekly early on, then semi-weekly for weeks three, four, and five, ensuring robust sampling during the highest risk period. He noted that similar measures for MAGNITUDE would be finalized with the FDA.

Brian Cheng of J.P. Morgan sought confirmation on whether the expanded MAGNITUDE study is now statistically powered to show a significant difference in the subset of patients on a stabilizer background.

Answer

President and CEO John Leonard provided a direct and affirmative response, stating, "The answer is yes."

Brian Cheng inquired about the key gating factors for the NTLA-2002 BLA filing in HAE, beyond the clinical data package, that need to be aligned ahead of the planned 2026 submission.

Answer

CEO John Leonard outlined that the preclinical package is complete, and importantly, the commercial form of the product is being used in the Phase III trial, avoiding bridging studies. He also highlighted the RMAT designation, which facilitates accelerated interactions with the FDA. An executive added that interactions with the FDA have been very favorable.

A representative for Brian Cheng asked how Intellia's NTLA-3001 for AATD is differentiated from competing RNA editing therapies, especially following recent data from peers.

Answer

CEO John Leonard asserted that the key differentiator for success will be achieving normal levels of wild-type protein. He emphasized that Intellia is the only company to have demonstrated this in non-human primates and that success for any approach will depend on delivery and durable protein production over time.

Brian Cheng inquired about the expected efficacy measures for the second-line pancreatic cancer (PDAC) trial (RASolute 302) at the top-line readout and requested more color on the rates of events.

Answer

Mark Goldsmith, Chairman and CEO, stated that Revolution Medicines is in the disclosure period and could not provide higher resolution details. He confirmed it is an OS (overall survival) event-driven readout, powered for OS, and thus overpowered for PFS (progression-free survival), with comparisons made against standard of care benchmarks.

Brian Cheng inquired about Revolution Medicines' latest thoughts on the efficacy measures expected at the top-line readout for the second-line pancreatic cancer (PDAC) trial (RASolute 302) and requested more color on the rates of events towards this upcoming top-line.

Answer

Chairman and CEO Mark A. Goldsmith stated that the company is in the period for disclosure and could not provide higher resolution details today. He confirmed that the readout is OS event-driven and powered for overall survival (OS), which means it is also overpowered for progression-free survival (PFS). He added that the analyses would directly compare against standard of care benchmarks.

Brian Cheng asked about the real-world responsiveness of R408W PKU carriers to current options like KUVAN, SEPHIENCE, or PALYNZIQ, and the expected uniformity of response to a base editing approach. He also inquired about the age range for the BEAM-304 Phase I/II study and the timeline to reach newborns.

Answer

CEO John Evans and Chief Medical Officer Amy Simon explained that R408W patients, having classic/severe PKU with near-zero PAH activity, typically do not respond to BH4 cofactors. While enzyme replacement therapies exist, they are cumbersome, and only about 60% of patients reach target levels after years, without full diet liberalization. For pediatric populations, they anticipate a staged approach, starting with older patients (18+ or 12+) and working with regulators to open younger cohorts based on accumulating data and PKPD modeling.

Brian Cheng asked about the real-world response of R408W PKU carriers to current options like Kuvan, Sephience, or Palynziq, and the expected uniformity of response to a base editing approach. He also inquired about the age range for the Phase I/II study and the timeline to include newborns.

Answer

CEO John Evans and CMO Amy Simon responded. Amy Simon clarified that R408W patients, having classic/severe PKU, would not respond to BH4/cofactors due to near-zero PAH enzyme activity. She noted that enzyme replacement therapies are cumbersome, with only about 60% of patients reaching target levels without full diet liberalization. For age ranges, she explained a typical staged approach, starting with adults and gradually opening to younger cohorts with regulatory collaboration and PKPD modeling.

Brian Cheng asked about PTC Therapeutics' expectations for Sephience's growth in Europe after the initial six-month free pricing period, specifically how the negotiated price is anticipated to balance out the projected increase in market uptake.

Answer

CEO Dr. Matthew Klein and Chief Business Officer Eric Pauwels explained that PTC is currently in the pricing and reimbursement process in Germany, leveraging strong clinical data, including INFINITY-AFFINITY and AMPLIFY, to support the highest possible price and lowest rebate. They anticipate these discussions to finalize over the next five to six months, with the goal of maintaining a strong list price.

Brian Cheng asked about Sephience's growth expectations in Europe after the six-month free pricing period, specifically how the negotiated price will balance out the projected market uptake.

Answer

Matthew Klein, CEO, and Eric Pauwels, Chief Business Officer, highlighted the strong launch in Germany with high center penetration. Pauwels explained that pricing and reimbursement discussions are ongoing for the next five to six months, leveraging strong clinical data (APHENITY and AMPLIFY) to support the highest possible list price and lowest rebate.

Brian Cheng of J.P. Morgan asked about early payer feedback on Sefiance and what it suggests for future contracting and net pricing. He also inquired about any significant inventory build for the launch and expected changes to the SG&A expense line.

Answer

Chief Business Officer Eric Pauwels reported positive payer feedback, noting the clinical profile is well-received with expectations for minimal restrictions and few step-edits. He stated it is too early for contracting discussions and that the payer mix is anticipated to be 65% commercial. CFO Pierre Gravier and CBO Eric Pauwels both confirmed no additional OpEx is expected as the launch leverages existing infrastructure, and there will be no inventory build, with specialty pharmacies carrying just-in-time inventory.

Brian Cheng asked about the latest thinking on the size and dose for the Brepo Phase 3 study in cutaneous sarcoidosis, the expected stability of efficacy from Phase 2 to Phase 3, and a follow-up on the return of certain batoclimab rights to HanAll and its read-through to TED data.

Answer

CEO Matt Gline noted a significant cushion in the Phase 2 data's quality. CEO Ben Zimmer added that while some erosion is possible, the large effect size provides confidence, and the Phase 3 size would likely be similar per arm to the DM trial, pending FDA discussions. Matt Gline clarified that the batoclimab rights return has no read-through to TED data, being a decision on future development with HanAll.

Brian Cheng, Executive Director and Senior Biotech Analyst at JPMorgan Chase & Co., asked about the anticipated size and dose for brepocitinib's phase 3 study in cutaneous sarcoidosis, the expected stability of efficacy from phase 2 to phase 3, and any read-through from the return of certain batoclimab rights to the upcoming TED data readout.

Answer

Matt Gline, CEO of Roivant Sciences, noted the significant cushion in the phase 2 data's quality. Ben Zimmer, CEO of Priovant, stated that while some erosion is possible, the large effect size provides confidence for phase 3, which would likely have a similar per-arm size to the DM trial, with 45mg reinforced as a compelling dose. Matt Gline clarified that the return of batoclimab rights has no read-through to the TED data, being a decision related to future development.

Miriam, on behalf of Brian Cheng from JPMorgan Chase & Co., asked how the extrathyroidal benefits in Graves' disease read through to the TED trial and about the updated timeline. She also inquired about the potential real-world sequencing of FcRn inhibitors in RA.

Answer

Executive Peter Salzmann stated that seeing proptosis changes in the Graves' trial (which had milder TED) is encouraging for the goal of treating TED earlier. He attributed the updated TED trial timeline to increased competition for eligible patients. Dr. Peter Taylor opined that for RA, FcRn inhibitors would likely be used in the difficult-to-treat population due to the prevalence of less expensive biosimilars and generics in earlier lines of therapy.

Speaking on behalf of Brian Cheng, an analyst asked how the extrathyroidal benefits from the Graves' trial read through to the ongoing Thyroid Eye Disease (TED) trial and about the updated timeline. A follow-up question for Dr. Taylor concerned the future sequencing of FcRn inhibitors in RA treatment.

Answer

Executive Peter Salzmann explained that while the TED trial population is more severe, seeing benefits in the milder Graves' population is encouraging for an early-treatment strategy. The TED timeline was updated due to high competition for a narrow patient group. Dr. Peter Taylor opined that due to the availability of cheaper biosimilars, FcRn inhibitors in RA would likely remain a therapy for the difficult-to-treat population, which represents the highest unmet need.

Brian Cheng inquired about Roivant's latest thinking on the size and dose for the brepocitinib Phase III study in cutaneous sarcoidosis, the expected stability of efficacy from Phase II to Phase III, and asked for more color on the return of certain batoclimab rights from HanAll.

Answer

Matt Gline, CEO of Roivant, and Benjamin Zimmer, CEO of Priovant Therapeutics, discussed the significant cushion in the Phase II data and the rigor of the multi-center study. Zimmer indicated a Phase III size similar to the DM trial is likely, pending FDA discussions, and reinforced confidence in the 45mg dose. Gline clarified that the return of HanAll rights has no read-through to the upcoming TED data, only to future development decisions for batoclimab.

Brian Cheng inquired about Roivant's latest thinking on the phase 3 size and dose for brepocitinib in cutaneous sarcoidosis, the expected stability of efficacy from phase 2 to phase 3, and the read-through of the return of certain batoclimab rights from HanAll to the upcoming TED data readout.

Answer

Benjamin Zimmer, CEO of Priovant Therapeutics, noted the significant cushion from phase 2 data and suggested a phase 3 size similar to the dermatomyositis trial, reinforcing the 45mg dose. Matt Gline, CEO of Roivant, clarified that the batoclimab rights return has no read-through to TED data, as it pertains to future development decisions with HanAll.

Brian Cheng inquired about the impact of Argenx entering the Graves' disease market on Roivant's 1402 strategy and what investors should expect from the upcoming Investor Day.

Answer

CEO Matthew Gline viewed Argenx's entry into Graves' disease as validation, emphasizing Roivant's competitive profile with higher-dose batoclimab and deeper IgG reduction. For Investor Day, he highlighted it as a moment of transformation to fully tell the business story, discuss commercial opportunities, and potentially share new updates.

Brian Cheng asked about Argenx's entry into the Graves' disease market and its impact on Roivant's 1402 strategy, and also what investors should expect from the upcoming investor day.

Answer

CEO Matt Gline acknowledged the competitive landscape in Graves' disease, noting Roivant's strong competitive profile with higher-dose Batoclimab and significant IgG reduction. He emphasized the large patient population and the validating nature of competition. Regarding the investor day, he stated it would focus on the business's transformation, commercial perspective, patient needs, and blockbuster opportunities, with potential for new updates.

Brian Cheng inquired about the upcoming top-line data release for brepocitinib in dermatomyositis (DM), the expected timeline for an FDA filing, and the rationale for testing a lower 300mg dose of IMVT-1402 in the second Graves' disease trial.

Answer

CEO Matt Gline stated that Roivant expects to share top-line, key secondary, and major safety data for the DM trial. He anticipates filing for approval in early 2026, with standard NDA preparation being the primary gating factor. Regarding the Graves' trial, Gline explained the lower dose is included to support discussions with the FDA about a minimally efficacious dose, aiming for a smoother regulatory process.

Brian Cheng of J.P. Morgan inquired about the definition of a successful outcome for the upcoming dermatomyositis (DM) trial and the focus of the June investor event. He also asked for clarification on the recent docket update regarding the narrowing of claims in the LNP litigation against Moderna.

Answer

CEO & Director Matt Gline explained that a "win" in the DM trial simply means a statistically significant separation from placebo, given the high unmet need. He stated the June event aims to educate investors on DM, trial endpoints, and the commercial opportunity. Regarding the litigation, Gline described the claim narrowing as a normal, procedural step to simplify the case for a jury trial and not indicative of any significant development.

Brian Cheng asked about Roivant's commitment to advancing IMVT-1402 into MG and CIDP irrespective of upcoming data, and sought details on the brepocitinib sarcoidosis trial's design and rationale.

Answer

CEO Matthew Gline responded that while they will use the data to inform development, MG and CIDP are large markets where IMVT-1402 has unique advantages in form factor and dosing, so the data isn't the sole determinant for proceeding. For the sarcoidosis trial, he reiterated it's a small, signal-finding study not powered for a specific statistical endpoint, noting the large effect size in a prior IIT study and a low expected placebo response.

Brian Cheng from JPMorgan Chase & Co. asked for specifics on the brepocitinib CLARITY Phase III trial design, including steroid dose requirements for entry, key patient stratification strategies, and the distinction between the CLARITY-1 and CLARITY-2 sub-studies.

Answer

Priovant CEO Ben Zimmer clarified that there is no specific steroid requirement for entry, allowing for a range up to 40mg/day or none at all. He stated there are no material stratification factors of note. The two sub-studies are primarily for assigning clinical sites, with some larger geographies participating in both while other countries are assigned to one or the other.

Brian Cheng of J.P. Morgan questioned if the 30% MRD conversion delta, a benchmark derived from later-line trials, is a fair bar for success in the earlier, first-line consolidation setting, suggesting the bar should be higher.

Answer

CEO Dr. David Chang defended the comparison, stating that the second-line randomized studies serve as a very good reference point, provided one equates MRD conversion with a complete remission (CR). He believes it's a solid benchmark for demonstrating a clinically meaningful benefit on EFS, while acknowledging the ultimate test is the ALPHA-three trial's outcome.

Brian Cheng from JPMorgan Chase & Co. inquired about the company's strategy for potentially using milder lymphodepletion or eliminating it entirely for ALLO-329, and the timeline to determine the optimal approach.

Answer

Dr. David Chang, President and CEO, confirmed the Phase I study for ALLO-329 is designed to answer this directly. It will include a cohort with milder lymphodepletion (cyclophosphamide only) and a parallel cohort with no lymphodepletion, allowing for a direct comparison to find the best path forward.

Sean on for Brian Cheng asked for more details on the Grade 5 adverse events reported for ALLO-316, including any confounding factors, and requested an explanation of how the management algorithm for IECHS is implemented and its ease of use for physicians.

Answer

Dr. David Chang, President and CEO, explained that the Grade 5 events are very confounded by patients' advanced metastatic disease and prior treatments. Dr. Zachary Roberts, EVP of R&D and CMO, described the IECHS management algorithm as a clear, two-step process analogous to those for CRS and ICANS, which has been easy to implement in the study. He noted that IECHS is now better understood as a spectrum of cytokine release syndrome, making management easier.

Brian Chung of JPMorgan Chase & Co. inquired about the importance and timing of securing a partner for the CHS-114 (anti-CCR8) program and asked for an update on the company's confidence in achieving its $150M-$200M revenue goal for Loktorzi.

Answer

Chief Medical Officer Rosh Dias outlined the data readout timeline for CHS-114, expecting efficacy and safety data in H1 2026. CEO Dennis Lanfear and Chief Scientific & Development Officer Theresa Lavallee emphasized their focus on finding the right partner to maintain development speed and leverage the asset's broad combinability. EVP of Commercial Sameer Goregaoker expressed high confidence in the Loktorzi revenue target, citing the strong uptake in academic centers following NCCN guideline updates as a key positive indicator.

Brian Cheng of J.P. Morgan sought clarification on the Phase 1 dose escalation design for ZW171, specifically asking if the initial dose level represented a range from 4.2 micrograms to 38 micrograms.

Answer

Chief Scientific Officer Paul Moore clarified the trial design, explaining that dose level one is not a range but a step-up dosing regimen where 38 micrograms is the target dose for that specific level.

Brian Cheng of JPMorgan asked about the potential impact of the ex-U.S. patient population on the zanidatamab Phase III HERIZON-GA trial outcome, referencing subset analysis from KEYNOTE-811. He also requested an update on the J&J KLK2 bispecific program and the financial terms of the partnership.

Answer

CEO Kenneth Galbraith addressed the trial question, stating that while a KEYNOTE-811 sub-analysis showed some variance, KOLs generally don't see significant efficacy differences across ethnicities, and the HERIZON-GA01 trial is globally diverse. Regarding the J&J partnership, he noted Zymeworks is entitled to future development milestones and a mid-single-digit royalty on sales of the KLK2 product, expressing optimism based on J&J's public comments.

Brian Cheng inquired about the efficacy criteria for advancing ZW171 and ZW191 to expansion stages, whether to expect data at the December R&D Day, and how to model near-term partnership revenue.

Answer

CEO Kenneth Galbraith clarified that the initial focus is on tolerability, and efficacy evaluation will include durability of response (DOR), which takes time. He explicitly stated not to expect initial clinical data at the R&D Day. For revenue modeling, he referred the question to partner Jazz Pharmaceuticals for guidance, as Zymeworks cannot disclose more than what is public in their agreements.

On behalf of Brian Cheng, Sean asked about the required response bar for the PRGN-2012 confirmatory trial and whether its enrollment must be completed prior to potential FDA approval.

Answer

President and CEO Dr. Helen Sabzevari explained that the confirmatory trial has a similar design and response bar as the pivotal Phase I and II studies, utilizing a single-arm, no-placebo design. She clarified that under the accelerated approval pathway, the trial only needs to be initiated at the time of BLA submission, not completed for approval. She also noted that the trial has already been initiated with strong patient interest.

On behalf of Brian Cheng, an analyst asked for clarification on the required response bar for the PRGN-2012 confirmatory trial and whether its enrollment must be completed prior to receiving FDA approval.

Answer

Dr. Helen Sabzevari, President and CEO, explained that the confirmatory trial's design and response criteria are identical to the pivotal Phase I and II trials, featuring a single-arm, non-placebo-controlled design. She clarified that under the accelerated approval pathway, the trial only needs to be initiated at the time of the BLA submission and completion is not a prerequisite for approval. She also noted enrollment has already begun with strong patient interest.

Asked about the expected launch trajectory for PRGN-2012, projected sales-related expenses, the company's cash runway, and the latest status on partnerships for the UltraCAR-T platform.

Answer

The company expects a 'relatively swift' launch uptake for PRGN-2012 due to a concentrated prescriber base. While commercialization will increase expenses, the company is managing costs and is confident in its ability to strengthen its balance sheet. The UltraCAR-T platform's advantages have created significant partnership excitement, and updates will be provided as they progress.

Asked about the timeline implications of the Phase I/II/III designation for the RUBY trial and for feedback from investigators on whether they are seeing early signs of clinical differentiation for Reni-cel.

Answer

The Phase I/II/III designation means it's a single study that can support a BLA, keeping them on track. Investigators are reportedly pleased with the correction of anemia, observing that patients are less fatigued and have more energy. They appreciate the potential for sustained normal hemoglobin levels to impact end-organ function, which is a key area of potential differentiation.

Asked for more specific timing on the XmAb564 psoriasis data and what efficacy benchmark (PASI score) would provide conviction for further development.

Answer

The company reiterated that the psoriasis study's primary goal is to gather biomarker data on Treg counts to inform dosing, not to achieve a specific PASI score. They are still guiding for data in 2024.