Kristen Kluska

Kristen Kluska from Cantor Fitzgerald asked about the early signals from Phathom's strengthened sales force and strategy, specifically regarding the conversion of new gastroenterologists and growth within existing GI accounts following their National Sales Meeting.

Answer

Steven Basta, President and CEO, highlighted consistent momentum, emphasizing the focus on growing writing frequency among GIs. He described an 'adoption ladder' where physicians move up in categories, noting a significant increase in physicians in upper writing categories. Basta also mentioned achieving over 20% penetration among the top few hundred writers, aiming for broader GI community conversion.

Kristen Kluska of Cantor Fitzgerald inquired about the specific sales force tactics to drive more depth and frequency of Voquezna prescriptions and asked about the real-world adoption pattern where physicians trial the drug on a few patients before broader use.

Answer

Steven Basta, President, CEO & Director, explained that Phathom has realigned its sales territories to focus entirely on gastroenterologists, increasing call frequency to build relationships and comfort with the product. He noted this strategy is effective because as physicians gain experience and hear positive patient feedback, it creates a self-reinforcing cycle of increased prescribing.

Representing Kristen Kluska from Cantor Fitzgerald, an analyst asked about the prescription contribution from non-erosive GERD patients and the split between 30- and 60-day scripts for VOQUEZNA.

Answer

President and CEO Steven Basta emphasized strong physician confidence in the product. CFO Molly Henderson added that while it's difficult to precisely track non-erosive vs. erosive use from claims data, the continued strong momentum in the 10mg dose suggests a significant contribution from the non-erosive indication.

Kristen Kluska asked for early metrics on refill trends and usage specifically for the Non-Erosive GERD (NERD) indication and how this might evolve with greater awareness.

Answer

CCO Martin Gilligan stated that overall refill rates are tracking as expected for a new launch and are in line with PPI persistency. He noted consistent refill rates for both the 10mg (NERD) and 20mg doses, with the 10mg dose growing faster, indicating strong uptake for the non-erosive indication and positive patient continuation.

Kristen Kluska questioned the role of efficacy in the long-term 15%-20% discontinuation rate and when a clear sense of efficacy-driven dropouts might emerge. She also asked about the nature of real-world efficacy, specifically if patients are responding to hyperphagia or behavioral improvements.

Answer

Anish Bhatnagar, Chairman and CEO, stated that patients who remain on therapy are likely to see benefits, and discontinuations due to lack of efficacy are currently few. He noted that real-world anecdotes primarily relate to changes in hyperphagia and its downstream effects, with some reports of improved calmness, social interactions, and reduced anxiety.

Kristen Kluska inquired about the long-term discontinuation rate of 15%-20% and how efficacy will factor into this, asking when the company will have a clear sense of patients dropping out due to lack of efficacy. She also asked if real-world efficacy anecdotes show differences in response (hyperphagia vs. behavior).

Answer

Anish Bhatnagar, Chairman and CEO, explained that patients who stay on therapy are likely to see benefits, and discontinuations for lack of efficacy are currently few. He noted that real-world anecdotes primarily relate to changes in hyperphagia and its downstream effects, with some reports of improved calmness and social interactions.

Kristen Kluska of Cantor Fitzgerald inquired about the real-world safety data observed since the launch and asked for broad guidance on revenue for the remainder of the year to help manage investor expectations.

Answer

CEO Anish Bhatnagar confirmed that no new safety signals have emerged in the post-marketing setting compared to the clinical trials, and discontinuation rates are lower. CFO Jim Mackaness acknowledged the strong Q2 revenue but suggested that the initial momentum might normalize over the next couple of quarters, without providing specific forward-looking guidance.

Kristen Kluska of Cantor Fitzgerald asked for an update on real-world safety data for VICAT XR and requested broad guidance on how to model revenue for the remainder of the year to manage expectations.

Answer

CEO Anish Bhatnagar confirmed that no new safety signals have been observed in the post-marketing setting compared to clinical trials, and discontinuation rates are lower. CFO Jim Mackaness noted that while Q2 performance was exceptionally strong, some normalization should be expected in the coming quarters, though momentum remains positive.

Kristen Kluska requested insight into how payer coverage decisions might differ on a state-by-state basis and asked about Soleno's planned presence at the upcoming International PWS Organization Conference.

Answer

Executive James MacKaness confirmed a significant presence at the upcoming PWS conference, involving commercial, medical affairs, and clinical teams. CCO Meredith Manning explained that through the Medicaid Drug Rebate Program (MDRP), states can begin coverage, but timelines vary. She noted that several states have already uploaded Vykat XR into their systems and are providing coverage.

Kristen Kluska requested insight into how state-by-state Medicaid coverage decisions might differ and asked about Soleno's planned presence at the upcoming International PWS Organization Conference.

Answer

Executive Anish Bhatnagar stated that Soleno will have a significant presence at the conference, with commercial, medical affairs, and clinical teams attending. CCO Meredith Manning explained that Soleno's participation in the Medicaid Drug Rebate Program (MDRP) allows states to add Vykat XR as of May 1, but policy adoption timelines vary by state, with several already providing coverage.

Kristen Kluska asked for more details on the profile of the second ONAPGO supplier, specifically their flexibility to add capacity if demand exceeds internal expectations, and the importance of this factor in the decision-making. She also sought clarity on the "month or so" timeline for FDA communication regarding the second supplier and when physicians would be confidently informed about increased supply.

Answer

Jack A. Khattar (President and CEO, Supernus Pharmaceuticals) stated the second supplier is their European partner with significant, larger capacity, and they are also discussing a third supplier to secure long-term supply. He clarified the "month or so" timeline is for further FDA communication on exact requirements for approval. He confirmed physicians are already being informed that new patient initiations have resumed, and the company is "pretty much at normal" for serving patients, though working through the backlog will take time.

Kristen Kluska asked for details on the profile of the second ONAPGO supplier, including its capacity flexibility for future demand, and the importance of this flexibility in the selection process. She also inquired about the timeline for clarity on FDA requirements for the second supplier's approval and when physicians would be informed about consistent ONAPGO supply.

Answer

Jack A. Khattar, President and CEO, explained that the second supplier is Supernus Pharmaceuticals' European partner, possessing significant experience and much larger capacity, with discussions for a third supplier also underway to ensure long-term supply. He indicated that more clarity on FDA requirements for approval would come within the next month or so. He confirmed that physicians have already been informed that the company is "back to normal" for processing forms and initiating new patients.

Kristen Kluska of Cantor Fitzgerald questioned the key drivers for new physician adoption of KELBRI following recent sales initiatives and asked about the company's pro forma cash position post-Sage acquisition and future M&A focus.

Answer

CEO Jack Khattar attributed KELBRI's success to a combination of factors, including a favorable label update clarifying its unique mechanism of action and a strong push into the adult segment. Regarding M&A, he confirmed that Women's Health is now a key area of interest alongside CNS. CFO Timothy Dec stated the company's pro forma cash position is between $240 million and $260 million.

Kristen Kluska asked about the prevalence of comorbidities in the ADHD patient population and how Supernus plans to penetrate that segment following the Qelbree label update. She also inquired about which therapeutic areas the company finds promising for business development.

Answer

CEO Jack Khattar noted that comorbidities like mood disorders affect 40-60% of ADHD patients. He explained that while the company cannot promote off-label, the label update provides important scientific information for physicians about Qelbree's unique mechanism. For business development, he said the company is interested in specialty areas like dermatology or urology and rare diseases, provided the opportunities offer scale through multi-asset situations.

Kristen Kluska from Cantor Fitzgerald inquired about Fulcrum's strategy for the upcoming FDA meeting regarding a registrational trial, specifically how they plan to balance expanding the total addressable market (TAM) with ensuring trial success, given recent challenges in the space.

Answer

Iain Fraser (SVP of Early Development) stated that the robust and consistent data supports advancing to a registration-enabling study, and they will discuss the role of HbF in an Accelerated Approval framework with the FDA. Alex C. Sapir (President and CEO) explained that studying a more severe patient population (e.g., those with more VOCs) aids powering and clinical success, and while the label might specify 'recurrent VOCs' or 'severe sickle cell disease,' it would likely allow physicians flexibility, potentially expanding the TAM beyond the 20% of patients currently meeting their strict inclusion/exclusion criteria.

Kristen Kluska inquired about Fulcrum's strategy for their upcoming FDA meeting, specifically how they plan to balance expanding the total addressable market (TAM) with ensuring trial success for a registrational study, given recent industry failures. She also asked what percentage of patients would fall under the 'recurrent VOCs' or 'moderate to severe' criteria if the label was broad.

Answer

Iain Fraser, SVP of Early Development, stated that the strong and consistent data supports advancing to a registration-enabling study, which will be discussed with the FDA, including the potential for Accelerated Approval based on HbF levels. Alex C. Sapir, President and CEO, explained that studying a more severe patient population aids powering and clinical success. He estimated that while current inclusion criteria cover about 20% of patients, a broader label for 'recurrent VOEs' or 'severe sickle cell disease' would significantly expand the addressable market, leaving interpretation to physicians and payers.

Kristen Kluska from Cantor Fitzgerald inquired about the drivers behind the faster-than-expected enrollment, asking if it was due to the discontinuation of Oxbryta or improved site activation. She also asked how a positive response in this severe, tough-to-treat population might translate to a broader patient population.

Answer

Executive Alexander Sapir attributed the strong enrollment to a combination of having the 'right' clinical sites, the unavailability of voxelotor (Oxbryta) prompting patients to seek alternatives, and overall excitement for HbF induction as a therapeutic strategy. Iain Fraser, Head of Development, added that overcoming the initial lag in site activation was key. Regarding translatability, Mr. Fraser noted that encouraging HbF responses were seen in less severe patients in the initial study, suggesting the benefit would extend to a broader population.

Kristen Kluska asked if recent data from another company using the reachable workspace (RSA) endpoint helps to de-risk it for FSHD, and also inquired about the size of the safety dataset and open-label extension data for the losmapimod NDA filing.

Answer

Executive Iain Fraser stated it is encouraging that other companies are using the RSA endpoint, reinforcing that the FDA has not suggested an alternative. CEO Alexander Sapir added that the other data validates the DUX4 pathway and the RSA endpoint. Sapir highlighted the large safety database of over 3,600 patients, and Fraser noted that extensive open-label data from both the Phase II (over 3 years) and Phase III REACH studies will be included in the filing.

Kristen Kluska inquired about the internal and external guidance for Sephience sales in 2026, specifically asking what assumptions are baked into the $700M-$800M product revenue guidance, the expected contributions from U.S. versus ex-U.S. markets, and whether the guidance is considered conservative at this early stage of the launch. She also asked about the dynamic of 'lost to follow-up' patients becoming aware of Sephience, how they are reached, and the trends observed within specialty centers, including physicians trying the therapy on more challenging patients first.

Answer

Chief Business Officer Eric Pauwels and CEO Dr. Matthew Klein clarified that the 2026 product revenue guidance of $700M-$800M primarily reflects Sephience sales, with the U.S. driving the vast majority of revenue. They noted that ex-U.S. contributions from 20-30 countries would be more meaningful in the second half of 2026 and beyond. Dr. Klein described the 'lost to follow-up' patients as being engaged through social media and community networks, dispelling the notion that they don't want therapy. He also confirmed that centers are initially trying Sephience on therapy-naïve or difficult-to-treat patients, with positive feedback encouraging broader adoption.

Kristen Kluska asked about the internal and external guidance for Sephience sales in 2026, specifically what's baked into the projections, the influence of launching in 20 versus 30 countries, and if the guidance is considered conservative. She also inquired about the dynamic of 'lost to follow-up' patients becoming aware of Sephience, how they are being reached, and trends observed within specialty centers regarding patient selection for initial treatment.

Answer

Matthew Klein, CEO, and Eric Pauwels, Chief Business Officer, explained that the $700M-$800M product revenue guidance for 2026 is primarily driven by Sephience, with the U.S. accounting for the vast majority. They noted that ex-U.S. contributions from 20-30 countries (including Japan and Brazil) are expected later in the year. Klein stated the guidance is conservative given the early stage of launch. Regarding 'lost to follow-up' patients, Klein clarified that these adults desire therapy and are being reached through social media and community networks. Centers are initially prioritizing therapy-naive or difficult-to-treat patients, with positive feedback, which is helping position Sephience as a first-line therapy.

Kristen Kluska of Cantor Fitzgerald inquired about the key objectives for the upcoming FDA meeting regarding the Huntington's disease trial design for vodoplan and whether new data would be presented. She also asked about the specifics of Translarna's European revenue under Article 117, including its renewal process and the sustainability of the projected 25% revenue.

Answer

CEO Dr. Matthew Klein stated the goal for the Huntington's program is to align with the FDA on the Phase III efficacy trial design and to clarify the pathway for accelerated approval, using either existing or future data from the open-label extension. Regarding Translarna, he explained that Article 117 allows individual European countries to make the drug commercially available despite the nonrenewal of the marketing authorization. He confirmed this has been adopted by about half the countries, securing roughly 25% of prior European revenue for the rest of 2025, but noted the duration is variable by country and does not require a centralized renewal.

Kristen Kluska inquired about the advanced state of FDA discussions for Sephience and the dynamics of patient interest, asking whether it was driven by treatment-naive or experienced patients.

Answer

CEO Dr. Matthew Klein confirmed that labeling discussions with the FDA for Sephience are far along and feel ahead of schedule, with no impact from recent agency changes. CBO Eric Pauwels added that patient interest is strong across all types, including naive and previously treated, driven by social media and engagement with the company's disease awareness website.

Kristen Kluska inquired about the patient expectations for diet liberalization with sepiapterin in PKU and asked for an overview of the market opportunity and launch cadence for vatiquinone in Friedreich's ataxia (FA).

Answer

CEO Dr. Matthew Klein highlighted that upcoming data will show over 97% of PKU patients on sepiapterin can liberalize their diet, which is a key driver for therapy adoption. For vatiquinone, Dr. Klein noted its potential as the first therapy for pediatric FA patients, while CBO Eric Pauwels detailed the launch strategy focusing on the unmet need in pediatrics and adults who cannot tolerate current therapies.

Kristen Kluska of Cantor Fitzgerald inquired about the specific definition of "identified patients," the treatment plan for patients outside the initial two Qualified Treatment Centers (QTCs), and the impact of patient-to-patient testimonials on commercial adoption.

Answer

CEO Vishwas Seshadri and CCO Madhav Vasanthavada explained that "identified patients" are those with severe RDEB and large, chronic wounds, as determined by physicians. They clarified that patients outside the initial QTCs are already being referred to the active centers. They also highlighted that testimonials from clinical trial participants in their "Strong Together" network have been highly effective in motivating new patients and families.

Kristen Kluska of Cantor Fitzgerald asked how Abeona plans to discuss the surgical procedure with physicians and whether it's seen as a barrier. She also questioned if the FDA's BLA review would focus solely on the new data addressing the CRL or encompass a full re-review of the entire application.

Answer

CEO Vishwas Seshadri and CCO Madhav Vasanthavada responded that surgeons do not view the procedure as a barrier, as it is not technically difficult and is supported by experienced cell therapy coordinators at the target treatment centers. Regarding the FDA review, Vishwas Seshadri stated that while they don't have a definitive answer yet, the assumption is the review will primarily focus on the new information submitted to address the CRL items, as is standard for the process.

Kristen Kluska of Cantor Fitzgerald inquired about the long-term revenue strategy of engaging with early-stage partners and the expected pace of revenue collection. She also asked if partners prefer Codexis to build capabilities in-house to avoid future tech transfers, and questioned the potential time and cost associated with this internal scale-up.

Answer

CEO Stephen Dilly confirmed the strategy is to secure a large number of early-stage assets, which will generate significant value as they mature, with revenue shifting from milestones to direct material supply. He affirmed that partners strongly prefer fewer transitions, making an in-house path attractive. He also noted a recent targeted cash top-up was designed to fund this scaling. CFO Georgia Erbez added that more clarity on the financial impact will be provided with 2026 guidance.

Kristen Kluska of Cantor Fitzgerald asked about Codexis's three core customer segments and what it will take to accelerate adoption of the ECO Synthesis platform among small and large siRNA drug innovators, who are currently slower to engage than CDMOs.

Answer

CEO Stephen Dilly explained that CDMOs are ideal early adopters due to their forward-planning nature and existing customer networks. He stated that to win over drug innovators directly, Codexis must execute on demonstrating key proof points: performance at scale, shorter production times, and the cost and speed advantages of building a GMP facility. Mr. Dilly emphasized that the company has moved from invention to execution, focusing on providing tangible evidence to potential customers.

Kristen Kluska of Cantor Fitzgerald inquired about the key parameters for evaluating success in the upcoming TIDES presentation, the level of detail expected in future partnership announcements, and any revenue expectations related to PAXLOVID.

Answer

SVP of Research Stefan Lutz identified overall yield and material quality (impurity profile) as the two key success parameters for synthesis. COO Kevin Norrett explained that partnership disclosure details will vary by partner, but the focus is on advancing projects to revenue generation. President and CEO Dr. Stephen Dilly stated that the company is not assuming any future revenue from PAXLOVID.

Kristen Kluska of Cantor Fitzgerald inquired about the segment of NPC patients who are diagnosed but not on therapy, the percentage of patients on paid Myclifa, and the reimbursement landscape for combination therapy.

Answer

Chief Commercial Officer Joshua Schafer explained that diagnosed but untreated patients were often identified before therapies were available and are now being re-engaged as awareness grows. President and CEO Neil McFarlane pointed to the 26% quarter-over-quarter revenue growth to $21.5 million as the key metric for paid drug conversion. Schafer added that since Myclifa's label is for use with miglustat, they have seen very limited reimbursement pushback on the combination, successfully using medical exception pathways for patients not yet covered.

Kristen Kluska inquired about the specific timing for the European marketing authorization application for MIPLYFFA, the nature of recent dialogues with the EMA, and how the mature European market might inform the U.S. launch strategy. She also asked about the assumptions behind the company's cash runway guidance.

Answer

President and CEO Neil McFarlane highlighted the European market potential with an estimated 1,100 patients and confirmed the plan to leverage MIPLYFFA's combination data with the established miglustat therapy. Chief Medical Officer Adrian Quartel added that the company is targeting an MAA filing in the second half of 2025, supported by new long-term data. Neil McFarlane also characterized the cash runway guidance, which excludes PRV proceeds, as an appropriately conservative estimate.

Kristen Kluska of Cantor Fitzgerald asked what Aquestive learned from reviewing the publicly available Complete Response Letter (CRL) issued to its competitor.

Answer

CEO Daniel Barber stated the primary lesson was the importance of closely following FDA guidance. He noted the competitor's CRL appeared related to an incomplete study. He contrasted this by highlighting that Aquestive's package was designed to be comprehensive, citing the inclusion of a repeat dose arm in its oral allergy syndrome study as specifically requested by the FDA.

Kristen Kluska of Cantor Fitzgerald questioned how the change in the FDA's division head for pulmonary and allergy might impact Anaphylm's review and a potential Ad Comm, and asked about other relevant personnel changes at the agency.

Answer

CEO Daniel Barber clarified that their primary interactions have been with the deputy division head, who remains in place along with the rest of the review team, so they do not believe the division head's retirement will have an impact. He stated that from a review standpoint, everything appears to be in a 'normal state.' Barber expressed that the company is prepared for and hopes for an Ad Comm but has some doubts about the government's ability to organize one.

Kristen Kluska asked for details on the company's pre-Advisory Committee preparations and about the potential for Anaphylm to penetrate the market of patients who previously avoided needle-based epinephrine products.

Answer

CEO Daniel Barber confirmed they have hired external experts and have a dedicated internal team preparing for a potential Ad Comm. He also noted a significant opportunity exists among individuals never prescribed a rescue product. Executive Sherry Korczynski predicted the market will shift from a 'needle vs. non-needle' to a 'devices vs. oral film' dynamic, which she believes will expand the market due to Anaphylm's convenience.

Kristen Kluska from Cantor Fitzgerald inquired about the timing of developmental milestone achievement, asking if gains occur at a specific point or over time, and whether the therapeutic benefits have plateaued.

Answer

Dr. Elsa Rossignol, a Principal Investigator for the REVEAL trials, responded that improvements and milestone gains are observed continuously over time at most follow-up visits, not just at a single point. She stated that the benefits have not plateaued and that some critical functional gains, such as walking with a walker, are not even captured by the specific milestone scale, indicating broader, ongoing improvements.

Kristen Kluska of Cantor Fitzgerald inquired about potential signals for a dose response with TSHA-102, asking whether time to treatment onset or specific endpoints could differentiate between high and low doses in the heterogeneous Rett syndrome population.

Answer

CEO Sean Nolan explained that Taysha will look for differentiation in the time to achieve functional gains and the overall magnitude of the response. President and Head of R&D Sukumar Nagendran added that translational data from animal models and the logical benefit of higher MECP2 protein levels also support the expectation of a superior clinical impact at the higher dose.

Kristen Kluska inquired about Taysha's regulatory strategy for TSHA-102, specifically how the company plans to use objective endpoints for the heterogeneous Rett syndrome population and how natural history data will be utilized as a potential comparator.

Answer

CEO Sean Nolan explained that the strategy involves trial designs where the patient may serve as their own control, supported by a completed natural history data analysis. He highlighted a focus on objective, functional gains and milestones, such as hand and gross motor function. President and Head of R&D Sukumar Nagendran added that the totality of clinical evidence will be crucial in discussions with the FDA.

Kristen Kluska asked how Taysha will determine if there is a dose response with TSHA-102, given the profound changes already seen with the low dose and the heterogeneity of Rett syndrome.

Answer

CEO Sean Nolan stated that preclinical data showed increased survival and improved gait at the high dose, and they expect to see consistent effects across clinical domains. He acknowledged the low dose set a high bar. President and Head of R&D, Sukumar Nagendran, added that while preclinical work justifies testing a higher dose, the ultimate goal is to find the ideal dose that regulators will approve and that will make the most difference for patients, which will be driven by the clinical data.

Kristen Kluska asked for clarification on the timeline of the Form 483 response acceptance, confirmed the HOPE-three timeline delay was due to waiting for FDA feedback, and inquired about the key goals for the upcoming Type A meeting.

Answer

CEO Linda Marbán clarified that the successful resolution of the Form 483 observations was handled by the FDA's inspection team independently of the CRL. She confirmed the HOPE-three timeline is paused pending FDA guidance and stated the primary goal of the Type A meeting is to understand the FDA's resistance to the current data and define the clearest path to approval.

Kristen Kluska of Cantor Fitzgerald asked about the key data drivers that convince physicians the drug's effects are not by chance, whether 4-year data will be ready for the AdCom, and about the stability of the FDA review team.

Answer

CEO Linda Marbán highlighted the statistical significance of cardiac MRI data as a key objective measure that requires few patients to show a treatment effect. She confirmed that promising 4-year open-label extension data will be presented at the PPMD meeting in June. She also expressed confidence in the FDA process, noting that key reviewers remain on the file and are actively engaged.

Kristen Kluska asked about the prevalence of cardiomyopathy in the non-ambulatory DMD population, potential safety protocols for commercial launch compared to gene therapies, and the company's manufacturing capacity to meet demand before the new facility is operational in mid-2026.

Answer

CEO Linda Marbán confirmed that most patients treated have been non-ambulatory, the population where cardiomyopathy is most manifest. She contrasted deramiocel's simple infusion and favorable safety profile with the complex care required for gene therapies, stating no extensive care team is anticipated. She also affirmed that the current facility, capable of servicing 250-500 patients annually, is sufficient to meet early launch demand until the expanded facility comes online.

On behalf of Kristen Kluska, Rick Miller asked for a definition of a clinically meaningful cardiac benefit in severe DMD patients, referencing recent World Muscle data, and inquired about the current patient journey for cardiac monitoring and how deramiocel's approval could impact it.

Answer

CEO Linda Marbán explained that while all patients showed benefit, the improvement was less pronounced in those with LVEF below 45% due to more existing scar tissue, highlighting the importance of early treatment. She described the patient journey, noting most children get a cardiac MRI before age 10, and that treatment could be triggered by either cardiac scar or a drop in ejection fraction. Marbán believes deramiocel's approval will accelerate and improve cardiac monitoring and treatment in the DMD community.

Kristen Kluska of Cantor Fitzgerald presented a hypothetical scenario, asking if strong data on pain reduction could support approval and adoption for the ORBIT study, even if the fracture data fell slightly below expectations.

Answer

Emil Kakkis, Founder, President & CEO, affirmed that the FDA considers the totality of data for rare disease programs. He stated that strong supportive data, such as on pain, would be helpful in any scenario. However, he reiterated his confidence that the fracture data will be strong, based on Phase II results showing very few fractures in patients established on the treatment.

Kristen Kluska asked about the OI trial, inquiring about the baseline age distribution as a potential variation factor and seeking clarification on whether results from the Cosmic study would be announced simultaneously with the Orbit study if the interim analysis is positive.

Answer

CEO Emil Kakkis and CMO Eric Crombez responded that the majority of patients in the trial are pediatric, with a smaller number of adults included to support a broad label. Regarding the data release, Kakkis stated that the reviews for the Orbit and Cosmic studies are not scheduled for the same day and the company has not yet decided if the results will be announced together.

Rick Miller, on behalf of Kristen Kluska, asked about the amended protocol for the DTX301 (OTC deficiency) trial, specifically regarding titration of standard care and what constitutes a meaningful ammonia reduction.

Answer

CEO Emil Kakkis and CMO Eric Crombez explained that patients are not expected to titrate down standard care during the blinded period due to safety concerns. A meaningful primary endpoint is the reduction of chronically elevated, cognitively impairing ammonia levels to the normal range. They drew a parallel to their GSD1A program, where patients reduced standard care only after entering an unblinded follow-up period.

Kristen Kluska asked for more color on the placebo arm in the setrusumab trial, including how the 20% efficacy assumption for bisphosphonates was developed and if placebo patients might experience more fractures due to increased activity from clinic visits.

Answer

CEO Emil Kakkis explained the 20% fracture reduction estimate for bisphosphonates comes from the two successful of five randomized studies. He noted the 67% reduction seen in their Phase 2 was on top of bisphosphonates. He agreed that increased travel for clinic visits could actually increase fracture incidence in the placebo arm, potentially widening the detectable difference between the groups.

Kristen Kluska from Cantor Fitzgerald asked for specifics on the growth levers that drove the significant prescription jump between April and May 2025. She also inquired about the top two or three selling points for new prescribers, beyond the primary focus on statin-intolerant patients.

Answer

President & CEO Sheldon Koenig attributed the growth to the focused strategy on statin intolerance. VP - Head Of Marketing Lisa Schafer added that growth was strong across Medicare and commercial channels, with improved Medicare out-of-pocket costs acting as a tailwind. Schafer identified the top selling points as NEXLETOL/NEXLIZET being the only products indicated for cardiovascular risk reduction in both primary prevention and statin-intolerant patients, a unique position in the market.

Asked about real-world use of the components of the triple therapy and physician interest in it, and inquired about the potential statin dosing strategy for the combination product.

Answer

The company confirmed that clinicians are already combining their drugs with statins in the real world. Their KOL advisory board is very enthusiastic about a formal triple combo. The likely strategy is to use lower doses of high-intensity statins to maximize efficacy while improving tolerability.

Kristen Kluska of Cantor Fitzgerald asked about the specific drivers that determine when a patient on Nexviazyme switches to Pombility/OpFolda—whether it happens at the two-year mark, earlier, or later.

Answer

President and CEO Bradley Campbell described the switching decision as a continuum, noting that earlier switches are often patients experiencing a clear decline on their current therapy. He expressed a long-term goal for Pombility/OpFolda to be established as the best therapy, leading to proactive switches. Chief Development Officer Dr. Jeff Castelli added that the pool of potential switchers will naturally grow over time as more patients on existing therapies experience disease progression.

Kristen Kluska of Cantor Fitzgerald inquired about the target patient population for DMX-200, asking what percentage of FSGS patients are poor responders to standard ARB therapy and might benefit from an inflammatory-focused mechanism.

Answer

Chief Development Officer Dr. Jeff Castelli explained that the DMX-200 trial targets the majority of FSGS patients who still have significant proteinuria despite standard care. He stated that higher proteinuria levels are likely indicative of an uncontrolled inflammatory component, making those patients prime candidates. While precise percentages are not yet known, they believe it is a significant portion of the over 40,000 FSGS patients in the U.S.

Kristen Kluska requested more details on the specific drivers that led to the company lowering its full-year operating expense guidance.

Answer

Chief Financial Officer Simon Harford attributed the reduced guidance to disciplined expense management, especially limiting new headcount by leveraging the existing Fabry commercial infrastructure for the Pombiliti launch. He confirmed that all key activities, such as registry studies and clinical trials, remain fully funded, and this financial discipline is a key factor in achieving non-GAAP profitability.

An analyst on behalf of Kristen Kluska asked for details on the Pombiliti and Opfolda prescriber mix, particularly the breakdown between large academic centers and community settings.

Answer

President and CEO Bradley Campbell reported a 50% increase in global prescribers in Q2, indicating strong growth in both breadth (new prescribers) and depth (repeat prescribers). He explained the mix varies by market: concentrated markets like the U.K. have all key centers prescribing, while in distributed markets like the U.S. and Germany, they are seeing strong uptake from top centers and are now penetrating more community-based physician practices.

Richard Miller, on for Kristen Kluska, asked for details on the natural history comparators used for the external control arm and whether to expect ENROL-HD data in the September update.

Answer

Chief Medical Officer Walid Abi-Saab explained that after assessing various databases, uniQure proposed using the ENROL-HD dataset as the comparator, and the FDA agreed this was the best fit. He confirmed the September data update will feature a comparison to an ENROL-HD control using propensity score matching.

Kristen Kluska inquired if questions from hospital VACs have remained consistent since the Analyst Day, particularly regarding cost. She also asked what percentage of the 45 interested hospitals had prior experience with Symvess through clinical trials.

Answer

CEO Dr. Laura Niklason and CCO BJ Scheessele confirmed the dialogue with VACs is consistent, focusing on clinical data and price. Mr. Scheessele noted the company's published Budget Impact Model effectively addresses cost concerns and that the ongoing NTAP application is also key. He stated that the minority (less than 50%) of the 45 hospitals were prior clinical trial sites, indicating strong interest from new centers.

An analyst on behalf of Kristen Kluska at Cantor Fitzgerald questioned the timeline for the Phase III trial in Peripheral Artery Disease (PAD) and the investment required, considering the company's current cash position.

Answer

Executive Laura Niklason affirmed Humacyte's commitment to the PAD program, highlighting the significant clinical need for patients who lack vein and require below-the-knee revascularization. However, she stated that the company is currently evaluating its cash position and long-term spending priorities following a recent capital raise before committing to a specific timeline for initiating the Phase III trial.

Kristen Kluska sought clarification on the AV access trial's co-primary endpoint structure, the company's confidence in the trial's size for a potential filing, and the sentiment from the surgical community following the release of the V007 data.

Answer

Executive Laura Niklason confirmed the trial had a co-primary endpoint at 6 and 12 months and a Special Protocol Assessment (SPA) with the FDA, increasing confidence in its design. She noted they will present the totality of data from both the V007 and older V006 trials to the FDA to support a filing. Regarding surgeon feedback, she observed that enrollment in the subsequent V012 women-only trial appears to be accelerating, suggesting increased investigator enthusiasm since the V007 results were publicized.

Kristen Kluska of Cantor Fitzgerald & Co. asked if the recent positive preclinical data has increased the company's conviction in the clinical trial's powering and expected outcomes for both monotherapy and combination arms.

Answer

CEO Punit Dhillon responded that while the robust preclinical results build confidence in the mechanism, they must be viewed with the caution that they are from mouse studies. However, he noted that DIO models have historically been good predictors in the obesity space. CSO Chris Twitty added that the team's confidence is further strengthened by carefully matching drug exposure levels in the DIO models to be clinically translatable to humans, making them feel confident Nimacimab will be an active drug.

Kristen Kluska inquired about the translation of preclinical data to predict 26- and 52-week weight loss curves, the specifics of the DSMB's safety review process for neuropsychiatric events, and the logistics behind the 52-week trial extension.

Answer

President and CEO Punit Dhillon explained the strategic decision for the trial extension was to gather robust long-term data, enabled by securing drug supply. CSO Christopher Twitty added that while preclinical models are being analyzed, historical data from drugs like rimonabant suggest an extension will allow for deeper weight loss. Punit Dhillon clarified that the DSMB reviews are independent and blinded to management, with the trial's continuation signaling no major safety concerns have been found.

Ian, on behalf of Kristen Kluska, asked for a detailed explanation of the mechanism behind central CB1 targeting's neuropsychiatric adverse events, how quickly these events were seen in other trials, and about the commercial use case for nimacimab in combination with GLP-1 therapies.

Answer

Chief Medical Officer Dr. Puneet Arora explained that blocking widespread CB1 receptors in the CNS impairs the body's natural stress and mood-balancing pathways, increasing the risk of anxiety and depression, with effects appearing relatively early in trials. President and CEO Punit Dhillon addressed the commercial question, reiterating that while combination use is being explored scientifically, the company's primary focus is securing regulatory approval for nimacimab as a monotherapy, which is the standard FDA pathway for new anti-obesity medications.

Rick Miller, on behalf of Kristen Kluska, asked for more detail on the administrative infusion delays, specifically the Medi-Cal issue that was mentioned as resolved.

Answer

President and CEO Douglas Ingram explained it was a specific administrative hiccup between sites in Los Angeles County and Medi-Cal regarding single-case agreements, which sites require for reimbursement assurance on high-cost therapies. This was not an access or prior authorization issue, but a delay in paperwork that pushed scheduled infusions from Q1 into Q2. Chief Customer Officer Dallan Murray added that such delays have a tenfold financial impact for a one-time gene therapy versus a chronic one.

Kristen Kluska from Cantor Fitzgerald asked about the limb-girdle muscular dystrophy (LGMD) portfolio, which she noted seems underappreciated, inquiring about the potential patient population and overall market opportunity.

Answer

President and CEO Doug Ingram highlighted the significance of the pipeline, stating that Sarepta's current LGMD portfolio represents an opportunity equivalent to about 70% of the Duchenne market. He specified that the near-term sarcoglycan programs alone are comparable to over 25% of the Duchenne opportunity, agreeing it is a major area of focus and value.

Kristen Kluska asked if the 2025 revenue guidance includes any contribution from a potential European approval and why peak sales are expected in a few years rather than sooner, like in 2026 or 2027.

Answer

CEO Douglas Ingram clarified that the provided 2025 revenue guidance is for U.S. sales only and does not assume any impact from a European approval. He explained that the revenue curve to peak sales is a function of the entire process, including site capacity and payer interactions, and reiterated that while 2025 will be strong, peak sales will occur some years after that as they treat the large prevalent population over the decade.

Kristen Kluska inquired about the ramp-up cadence for third-party plasma supply contracts, the current status of the ASCENIV patient waiting list, and the adoption rate of ASCENIV by physicians after initial use.

Answer

President and CEO Adam Grossman stated that the onboarding of third-party supply centers is progressing rapidly, exceeding 50% completion and beating internal estimates, which could lead to upside in 2026 guidance. He confirmed the queue of prospective ASCENIV patients is growing, and the company is accelerating new patient starts as plasma supply increases. Grossman also noted that physicians who try ASCENIV with one or two patients often queue up several more, indicating significant growth potential within existing clinics.

Kristen Kluska from Cantor Fitzgerald inquired about the drivers behind ADMA's newly stated $1 billion revenue potential for ASCENIV and sought specific metrics on the VIP donor program's impact on high-titer plasma collection.

Answer

President and CEO Adam Grossman explained that strong demand, coupled with a VIP donor program and the ADMAlytics platform, is accelerating the identification and retention of high-titer plasma donors, which is the primary constraint on ASCENIV's growth. He noted the company has strategically shifted production from BIVIGAM to ASCENIV and is working with third-party collectors to expand supply. While declining to share specific metrics on the VIP program, he confirmed it is active in all 10 centers and is improving donor frequency and retention. CFO Brad Tade added that the company will pursue the $1 billion target as rapidly as possible, with further growth headroom expected thereafter.

Representing Kristen Kluska of Cantor Fitzgerald, an analyst asked how partner Roche might utilize the recently obtained RMAT designation for OpRegen and whether Lineage could receive milestones upon completion of the ongoing Phase IIa study.

Answer

CEO Brian Culley explained that while he doesn't know Roche's specific plans, RMAT designation provides significant advantages, such as more frequent FDA meetings and discussions on novel endpoints. He confirmed that Lineage remains eligible for all $620 million in developmental and commercial milestones from the Roche partnership, but the specific triggers and amounts are confidential and not factored into cash runway guidance.

Kristen Kluska of Cantor Fitzgerald inquired about the key criteria that made physicians comfortable reducing G-CSF usage in the Phase II trial and asked for any anecdotal evidence of patient benefits like reduced pain or improved convenience.

Answer

CEO Paula Ragan and Chief Medical Officer Christophe Arbet-Engels explained that physicians' confidence to lower G-CSF doses stemmed from the high and robust Absolute Neutrophil Count (ANC) responses observed after adding mavorixafor. They noted that this decision was at the discretion of physicians and patients, with 75% choosing to reduce the dose. They stated it was too early to provide specific anecdotes on patient-reported outcomes like pain reduction.

Kristen Kluska inquired about how physicians will measure XOLREMDI's success in a commercial setting versus a clinical one, and asked about the status of ex-U.S. partnership discussions for mavorixafor, including whether potential partners have shown interest in other indications beyond WHIM syndrome.

Answer

Chief Commercial Officer Mark Baldry explained that physicians are primarily focused on XOLREMDI's impact on reducing infections, which is the key value driver. Chief Financial Officer Adam Mostafa confirmed that partnership discussions are ongoing and that interest is growing following the U.S. approval and positive Phase II data in chronic neutropenia.

Kristen Kluska asked about the key drivers for new patient starts for TAVALISSE and how Rigel plans to balance financial discipline with its growth strategy, particularly concerning future business development deals.

Answer

Chief Commercial Officer David Santos attributed TAVALISSE's growth to a continuous flow of new patient starts from both new and existing prescribers, as well as increasing use in earlier lines of therapy. President and CEO Raul Rodriguez stated that future acquisitions will be similar to REZLIDHIA and GAVRETO—hematology/oncology focused, leveraging existing infrastructure, and near-term to market. David Santos added that the commercial team's ability to manage a multi-product portfolio has matured, giving them confidence to execute on a more complex portfolio.

Kristen Kluska of Cantor Fitzgerald inquired about the rationale for partnering the ImmTOR-IL program instead of pursuing IND-enabling studies internally, and also asked for details on the updated cash runway guidance.

Answer

CEO Carsten Brunn explained that the decision was driven by the significant development costs and timelines required for the pipeline assets versus the high value of SEL-212. Executive Blaine Davis clarified that the cash runway guidance, extending into 2027, conservatively includes only the next regulatory milestone and does not account for future milestones or royalties from the SEL-212 program.

Kristen Kluska asked about the market opportunity for ImmTOR IL in PBC and the broader liver disease space, and how its mechanism might address unmet needs like ALP normalization and pruritus. She also questioned if the pause of the MMA trial was purely a strategic prioritization and what would be required to advance the program.

Answer

CEO Carsten Brunn described the liver disease market as a 'sweet spot' for Selecta, being large enough to be meaningful but manageable for internal development and commercialization. CMO Peter Traber added that the addressable market includes over 100,000 U.S. patients who fail current therapies and that evolving treatment goals, like ALP normalization, expand the opportunity. Regarding the MMA trial, Carsten Brunn confirmed the pause was strictly a resource allocation decision to preserve capital and that the program is 'ready to go' for a potential partner.

Kristen Kluska inquired about the market opportunity for PBC and the broader liver space for ImmTOR IL, and how the mechanism might impact disease manifestations like ALP normalization. She also asked for confirmation that the MMA trial pause was purely a strategic prioritization and what would be required to advance the program.

Answer

CEO Carsten Brunn described the liver disease market as a 'sweet spot' for Selecta. CMO Peter Traber quantified the U.S. patient population at approximately 280,000, with over 100,000 needing new therapies, and noted that evolving endpoints like ALP normalization favor their immunologic approach. Mr. Brunn confirmed the MMA trial pause was a resource prioritization decision with no issues with the program, stating it is a 'turnkey' opportunity for a potential partner.

Kristen Kluska inquired about the market size for PBC and the broader liver disease space for ImmTOR IL, and how the drug's mechanism might address endpoints like ALP normalization. She also sought confirmation that the pause of the MMA trial was purely a strategic prioritization and asked what is needed to advance the program.

Answer

CEO Carsten Brunn described the liver disease market as a 'sweet spot' for Selecta. CMO Peter Traber quantified the U.S. market of patients failing current therapies at over 100,000 and noted that evolving endpoints like ALP normalization favor their approach. Brunn confirmed the MMA trial pause was a resource allocation decision, not due to program issues, and that the program is 'ready to go' for a potential partner.

Kristen Kluska of Cantor Fitzgerald asked about the market opportunity for PBC and the liver space, how ImmTOR IL might impact endpoints like ALP normalization, and the rationale for pausing the MMA gene therapy trial.

Answer

CEO Carsten Brunn described the liver disease market as a 'sweet spot' for Selecta. CMO Peter Traber added that over 100,000 U.S. patients fail current therapies and that evolving standards like ALP normalization favor an immunologic approach. Regarding the MMA trial, Brunn clarified the pause was a strategic decision to prioritize resources and preserve cash, not due to any issues with the program, and that the company is seeking a partner.

Kristen Kluska from Cantor Fitzgerald asked how the upcoming MMA data and regulatory discussions could enhance conversations with partners, questioned the increase in general awareness of the ImmTOR platform, and inquired about the number of liver diseases ImmTOR-IL could target and the criteria for selecting an initial indication.

Answer

President and CEO Carsten Brunn stated that having a clear regulatory path and data from the MMA study provides a valuable blueprint for partners. He noted that setbacks in the broader gene therapy field have increased awareness of ImmTOR as a solution. Chief Medical Officer Peter Traber added that potential liver disease targets include PBC, autoimmune hepatitis, and PSC, all of which represent significant unmet medical needs.

Kristen Kluska from Cantor Fitzgerald asked how upcoming MMA data could enhance partnership discussions, questioned the growing awareness of the ImmTOR platform, and inquired about the number of liver diseases ImmTOR-IL could target and the criteria for selecting an initial indication.

Answer

President and CEO Carsten Brunn explained that having a clear regulatory path and clinical data from the MMA study provides a valuable blueprint for partners. He confirmed awareness of the platform is increasing due to its potential to solve key gene therapy challenges like redosing and AAV toxicity. Chief Medical Officer Peter Traber added that ImmTOR-IL could target several autoimmune liver diseases with high unmet need, such as PBC, autoimmune hepatitis, and PSC, and that more detail on indication selection would follow the DISSOLVE data release.

Kristen Kluska of Cantor Fitzgerald inquired about Chemomab's 2023 medical conference strategy and the scope of ongoing partnership discussions, particularly regarding NASH.

Answer

Co-Founder and CSO Dr. Adi Mor detailed plans for presentations at EASL and EULAR, with potential late-breaking NASH data. Chairman & CEO Dale Pfost confirmed that partnership dialogues include NASH, leveraging encouraging data, even as the company's internal focus remains on PSC and SSc.

Kristen Kluska of Cantor Fitzgerald inquired about the planned systemic sclerosis (SSc) trial, asking about the percentage of patients with high CCL-24 levels, the expected disease severity of this group, and any other symptoms that correlate with elevated CCL-24. She also asked for feedback from recent scientific presentations.

Answer

Interim CMO Dr. David Weiner explained the trial will enrich for patients with high CCL-24 levels, likely the top 70-75th percentile, to avoid impairing enrollment. Co-Founder and CSO Dr. Adi Mor added that higher CCL-24 levels correlate with pulmonary, vascular, and fibrotic manifestations, indicating a more active patient population. Dr. Mor also noted positive feedback from the Anti-fibrotic Drug Development Summit, particularly regarding the CM-101 data from the COVID-19 lung injury study.

Kristen Kluska of Cantor Fitzgerald inquired about how CM-101's dual action on inflammation and fibrosis differentiates it from prior failed drugs in PSC and SSc, what to expect from the upcoming PSC interim readout, and what endpoints are being considered for the SSc trial.

Answer

Co-Founder & CSO Adi Mor explained that CM-101's unique mechanism targets fibrosis, Type 2 immunity, and other disease-specific pathologies, offering a key differentiation. Interim CMO Dr. David Weiner clarified the PSC interim analysis is primarily for safety to support dose escalation and to assess biomarker variability for sample size confirmation, not for efficacy. He added that details on the SSc trial design and endpoints will be provided in August.

Kristen Kluska of Cantor inquired about the timing and rationale for acquiring all of RubrYc's assets, questioning what new information or diligence led to the decision versus the original partnership agreement. She also asked about the expected clinical development cadence for other pipeline programs following IBIO-101.

Answer

Chairman and CEO Tom Isett explained that a year of hands-on experience with the RubrYc platform through a joint discovery agreement on 'Target 6' provided real-world validation and confidence in the technology's strength. Chief Scientific Officer Martin Brenner added that the successful progression of Target 6 served as a key proof-of-concept. Regarding the pipeline cadence, Tom Isett stated that a comprehensive portfolio review is underway to prioritize assets and manage cash, with the attractive IBIO-101 program remaining the foremost priority.

On behalf of Kristen Kluska from Cantor Fitzgerald, a representative asked about the recent IBIO-101 poster data, specifically questioning the binding kinetics and effective concentrations of the plant-produced versus CHO cell-produced versions. He also inquired about the expected cadence of updates as IBIO-101 moves into IND-enabling studies.

Answer

Chairman and CEO Tom Isett confirmed that the similar binding kinetics between the plant-made and mammalian-made IBIO-101 were the expected and desired outcome, demonstrating platform comparability. He clarified that the afucosylated versions from both platforms performed similarly and were superior to fucosylated versions, as anticipated. For future updates on IBIO-101, Isett guided to expect toxicology data, a potential publication on in-vivo efficacy, and other data presentations at conferences and via press releases over the next 6-9 months.

Kristen Kluska of Cantor Fitzgerald inquired about iBio's oncology pipeline, specifically seeking details on the validation of undisclosed targets like Target 6, the company's strategy for precision medicine, and how its platform technologies could accelerate development timelines for both oncology and its COVID-19 vaccine.

Answer

CEO Tom Isett and CSO Martin Brenner explained that their oncology strategy focuses on clinically validated but challenging targets, like CD25 and Target 6, where their technology can improve safety and efficacy. For Target 6, they are using AI to create antibodies specific to mutated proteins on tumor cells. Regarding precision medicine, Tom Isett noted the FastPharming platform's modularity is ideal for rare cancers. He also affirmed that their integrated platforms are expected to significantly reduce development time and cost, with a goal to file an IND for the IBIO-202 COVID vaccine by the end of the calendar year.

Kristen Kluska from Cantor Fitzgerald inquired about the rapid identification of a new pipeline target with RubrYc, the potential for lowering the IBIO-202 vaccine dose, and the supply chain advantages of iBio's plant-based manufacturing.

Answer

CEO Thomas Isett and CSO Martin Brenner explained that the new RubrYc target was selected for its synergy with both iBio's FastPharming/Glycaneering and RubrYc's AI platforms. Isett clarified that the current IBIO-202 FDA submission is for intramuscular delivery, while dose-lowering and microarray patch delivery are part of a separate, long-term platform strategy. He also highlighted that iBio's plant-based upstream manufacturing avoids reliance on single-use plastics, mitigating some supply chain risks faced by competitors.

Kristen Kluska asked for more detail on the decision to delay the registrational study to H2 2023, how the recent data might correlate to the once-daily Aramchol meglumine profile, and for an update on the development plans for Amilo-5MER, particularly regarding IBD.

Answer

President and CEO Allen Baharaff explained the delay is to await more clarity on regulatory endpoints, non-invasive biomarkers, and study design to de-risk the pivotal trial. He noted Aramchol meglumine offers a once-daily dosing advantage with the same active moiety. For Amilo-5MER, he confirmed they are assessing proof-of-concept studies for IBD, potentially in combination, and also exploring other inflammatory indications like FMF.

Kristen Kluska from Cantor Fitzgerald asked for details on the timeline for the planned pharmacology studies for Aramchol meglumine, whether the new formulation would be used in future combination trials, and how the extended IP portfolio impacts the company's commercialization and partnership strategy.

Answer

Chief Scientific Officer Dr. Liat Hayardeny outlined the three planned clinical pharmacology studies. President and CEO Allen Baharaff added that the timeline for starting the next trial is dependent on formulation manufacturing but is targeted for the end of Q1 2022. He confirmed Aramchol meglumine will be used in all future studies and stated that the company is actively seeking various forms of partnerships, viewing the current stage as an ideal entry point for a collaborator.

Kristen Kluska of Cantor Fitzgerald inquired about the specifics and timing of the planned pharmacology studies for Aramchol meglumine, whether this new formulation would be used in future combination studies like the one with ASC41, and how the extended IP portfolio might alter the company's commercialization strategy.

Answer

Chief Scientific Officer Liat Hayardeny detailed three planned pharmacology studies: dose-range finding, food effect, and bioavailability. Executive Allen Baharaff added that the timeline for starting the next trial phase (Q1/Q2 2022) depends on formulation development. He confirmed Aramchol meglumine will be the go-forward product for all future studies, including combinations, and that the company is actively open to commercial partnerships before the double-blind study begins.

Kristen Kluska of Cantor Fitzgerald asked about expectations for the placebo response rate in the upcoming CSU study and what the company would define as a successful efficacy outcome. She also inquired about the strategic learnings anticipated from expanding CDX-0159 into eosinophilic esophagitis (EoE) and how it could inform the broader platform.

Answer

SVP and CMO Diane Young projected a placebo response between 20-40% and defined success as achieving efficacy similar to or better than Xolair, aiming for a ~50% response rate on UAS7 with a significant portion being complete responses, even in Xolair-refractory patients. She explained that the EoE indication is valuable because routine biopsies in these patients will provide direct evidence of CDX-0159's effect on tissue mast cells in the GI tract, potentially opening pathways to other gastrointestinal diseases.

Kristen Kluska from Cantor Fitzgerald inquired about the CDX-0159 program, including the evaluation of comorbidities, the influence of CIndU trial data on selecting a third indication, and patient criteria for upcoming trials regarding antihistamine and Xolair use. She also asked for specifics on the upcoming CDX-1140 data release and for guidance on future spending trends following pipeline adjustments.

Answer

SVP and Chief Medical Officer Diane Young confirmed the company intends to track comorbidities and that data from the CIndU study will inform the selection of the third indication for CDX-0159. SVP of Regulatory Affairs Margo Heath-Chiozzi clarified that patients must have failed standard antihistamine doses but not necessarily higher ones, and that prior Xolair use is permitted in the CSU trial. CFO Sam Martin stated that spending changes are already factored into the financial guidance, which provides a cash runway through 2023.

Kristen Kluska from Cantor Fitzgerald asked about the long-term cost and time savings from manufacturing improvements, the collaboration with ABB on robotics, and the criteria for selecting the next clinical indications beyond AML.

Answer

Chief Development Officer Dr. Juan Vera explained that the simplified manufacturing process will have a significant positive impact on product cost and serves as a solid foundation for future commercialization and optimization. Regarding robotics, both CEO Peter Hoang and Dr. Vera expressed excitement about the ABB collaboration to improve consistency and remove operator variability. On future indications, CMO Dr. Mythili Koneru and Mr. Hoang noted that while pancreatic cancer and lymphoma data are promising, the company's current focus remains on the AML trial.