Jonathan Chang

Jonathan Chang asked about the anticipated impact of receiving the FDA Commissioner's National Priority Voucher on Diraxonrasib's regulatory timelines and overall development plans.

Answer

Mark Goldsmith, Chairman and CEO, expressed pride in receiving one of the first nine vouchers, noting it's the only oncology product in that set. He highlighted the voucher's goal to accelerate review timelines, potentially to one to two months, and affirmed the company's aggressive preparation for data readout, NDA submission, and product launch, anticipating no difficulties in meeting accelerated timelines.

Jonathan Chang asked about the impact of receiving the FDA Commissioner's National Priority Voucher on Diraxonrasib timelines and the company's plans.

Answer

Mark Goldsmith, Chairman and CEO, stated the company is proud to receive one of the first nine vouchers, which aims to accelerate review timelines, potentially to one to two months. He confirmed they are aggressively preparing for data readout, NDA submission, and launch, and do not anticipate any difficulty meeting potential accelerated timelines.

Jonathan Chang of Leerink Partners requested more detail on the type and amount of doraxonerasib combination data expected later this year to inform the frontline PDAC study design. He also asked about the key considerations for selecting the specific chemotherapy regimen for that registrational study.

Answer

CEO Mark Goldsmith explained that the company will share a data set sufficient to justify their decision-making for the trial. President of R&D Steve Kelsey reiterated that the primary consideration is minimizing dose interruptions and maximizing the dose intensity of the RAS inhibitor, while using standard, globally accepted chemotherapy drugs and schedules.

Jonathan Chang of Leerink Partners asked about the company's perspective on the potential duration of clinical benefit for the multi-selective inhibitor daraxonrasib versus mutant-selective inhibitors like zoldonrasib and elironrasib, and how this comparison influences development strategy.

Answer

Dr. Stephen Kelsey, President of R&D, explained that duration of benefit is the primary consideration. He noted that the mechanisms of escape from multi-selective and mutant-selective inhibitors are different, which is the core rationale for combining them. The combination is expected to cover these different escape pathways, leading to a longer PFS than either agent alone, with the high response rate being a positive early indicator. Dr. Mark Goldsmith, CEO, added that this is consistent with preclinical findings.

Jonathan Chang requested more color on what is included in the company's cash runway guidance, particularly concerning the various potential development paths in pancreatic and lung cancer.

Answer

Jack Anders, CFO, explained that the cash runway guidance, which extends into 2027, fully incorporates the costs for the two disclosed Phase III second-line studies in pancreatic and lung cancer. For other potential programs and future pivotal trials, the company uses a probability-adjusted model, so specific additional programs are not explicitly detailed in the forecast.

Jonathan Chang of Leerink Partners asked for details on the scenarios being explored to enhance liquidity and maximize shareholder value, and what opportunities related to XPOVIO are being considered.

Answer

CEO Richard Paulson reiterated the company's previous disclosures, stating that Karyopharm is exploring a full range of financing and strategic alternatives with the help of its advisor, Centerview Partners. He clarified that the company does not intend to disclose further developments until the board approves a specific action, and confirmed that the process encompasses the totality of the XPOVIO asset.

Jonathan Chang of Leerink Partners inquired about the enrollment progress for the Phase III endometrial cancer study. He also asked for clarification on the company's cash runway guidance in relation to the timelines for its key Phase III data readouts.

Answer

Chief Medical Officer Reshma Rangwala reported that enrollment in the global endometrial cancer trial is progressing well, with strong interest in the novel p53-defined population, keeping it on track for a mid-2026 data readout. Chief Financial Officer Lori Macomber reiterated that the company is exploring various financing and business development options, including partnerships on early-stage assets, debt management, and potential equity raises, to ensure it is well-capitalized through its major data readouts.

Jonathan Chang inquired about the progress of regulatory interactions for Zifdomenib ahead of its PDUFA date and the strategic scope of the farnesyltransferase inhibitor (FTI) opportunity, including which programs Kura might develop alone versus with a partner.

Answer

Chief Medical Officer Dr. Mollie Leoni confirmed that FDA interactions for Zifdomenib have been collaborative and constructive, aligning with the priority review timeline. CEO Dr. Troy Wilson and Dr. Leoni added that the FTI program aims to reshape the field by using combinations to overcome resistance in areas like RCC, PI3 kinase, and KRAS, with potential for broad applicability.

Jonathan Chang of Leerink Partners inquired about any impact from regulatory agency changes on ziftomenib's approval timeline and asked for expectations regarding the upcoming ASCO presentation of KOMET-001 data, specifically the difference between the abstract and the full presentation.

Answer

CEO Troy Wilson stated that Kura has not experienced any disruptions from FDA changes, highlighting the drug's Breakthrough Therapy Designation. He confirmed the ASCO abstract and presentation will use the same data cutoff, but the oral presentation will offer a more comprehensive dataset, with the CR/CRh rate expected between 20% and 30%.

Jonathan Chang from Leerink Partners inquired about how emerging long-term data for ziftomenib and other menin inhibitors is shaping the company's view on the class's potential and the key factors determining patient treatment duration.

Answer

CEO Dr. Troy Wilson emphasized the significance of the frontline setting, highlighting that in the 7+3 adverse risk cohort, a high percentage of patients remained on therapy after a year. He stated the major commercial opportunity is in treating patients early and keeping them in response for extended periods (12-18+ months), a potential suggested by the emerging data.

Jonathan Chang of Leerink Partners asked about Epkinley's competitive positioning against other CD20 bispecifics following the positive Phase III EPCORE FL1 results.

Answer

Chief Medical Officer Tahamtan Ahmadi highlighted Epkinley's broad development plan, head start in second-line follicular lymphoma, and strong data generation. Chief Commercial Officer Brad Bailey noted its leading sales position and dual-indication approval. CEO Jan van de Winkel added that numerous abstracts have been submitted for the upcoming ASH meeting.

Jonathan Chang of Leerink Partners asked about the competitive positioning of Epkinley (epcoritamab) against other CD20 bispecifics, considering both clinical development and commercial experience following the positive Phase III EPCORE FL1 results.

Answer

Tahamtan Ahmadi, EVP & Chief Medical Officer, highlighted Epkinley's broad development plan, its head start in second-line follicular lymphoma, and strong data generation. Brad Bailey, EVP & Chief Commercial Officer, emphasized its leading global sales position as the only off-the-shelf dual indication bispecific, noting positive physician feedback and expanding community uptake. CEO Jan van de Winkel added that numerous abstracts were submitted for the upcoming ASH meeting.

An analyst on behalf of Jonathan Chang inquired about expectations for the upcoming Rina-S endometrial cancer data at ASCO and the comparative commercial opportunity of Rina-S in endometrial versus ovarian cancer.

Answer

CMO Tahamtan Ahmadi, while under embargo, described the upcoming Rina-S data as 'very compelling' and supportive of a best-in-class profile. CFO Anthony Pagano elaborated on the commercial potential, framing it as a key component of a potential '$2 billion-plus opportunity' for the asset, building on the progress made since its acquisition. CCO Brad Bailey added that Rina-S is viewed as a primary future growth driver for Genmab.

Jonathan Chang of Leerink Partners inquired about the commercial opportunity for bemarituzumab in frontline gastric cancer, including necessary biomarker status and the observed safety profile. He also asked about Zai Lab's confidence in achieving its 2025 revenue guidance and year-end profitability goal, specifically questioning the role of VIVGART in reaching these targets.

Answer

Josh Smiley, President & COO, outlined a potential billion-dollar sales opportunity for bemarituzumab in China, targeting the one-third of gastric cancer patients overexpressing FGFR2b. Rafael Amado, President and Head of Global R&D, specified the biomarker cutoff and described the expected ocular toxicity as manageable. Regarding guidance, Josh Smiley reaffirmed the full-year revenue target of $560-$590 million and the goal of Q4 non-GAAP profitability, attributing confidence to accelerating VIVGART growth and the stabilization of ZEJULA sales.

Yen-Der Li, on behalf of Jonathan Chang, asked about the potential impact of recent FDA changes and U.S. tariffs on Zai Lab's business, and requested details on the pivotal trial design for ZL-1310 in small cell lung cancer.

Answer

Joshua Smiley, President and COO, stated no anticipated impact from tariffs due to local manufacturing strategies. Dr. Rafael Amado, President and Head of Global R&D, noted no changes in their interactions with the FDA. Jonathan Wang, CBO, described the ZL-1310 trial as a randomized study designed for accelerated approval based on response rate, with overall survival as the final endpoint.

Yen-Der Li, on behalf of Jonathan Chang, asked for clarification on the regulatory strategy for ZL-1310, specifically whether the pivotal study for accelerated approval would be single-arm or randomized, and how the timeline compares to competitors like tarlatamab.

Answer

Dr. Rafael Amado, President and Head of Global R&D, stated that while he could not disclose details of FDA discussions, both single-arm and randomized trial pathways exist for accelerated approval. He reiterated confidence in a potential 2027 approval, noting ZL-1310's higher response rate (70% vs 40%) gives them a strong position relative to tarlatamab.

Jonathan Chang of Leerink Partners asked for expectations on the upcoming clinical data for the DLL3 ADC, ZL-1310, and questioned the company's broader strategy for expanding its global portfolio beyond in-licensing.

Answer

Dr. Rafael Amado, President and Head of Global Oncology R&D, stated that the ZL-1310 dose-escalation trial is progressing well, with initial data expected in late 2024 or early 2025. He also highlighted the company's internal discovery efforts, which aim to generate at least one global IND per year, complementing their business development strategy.

Jonathan Chang from Leerink Partners questioned the company's path to profitability, including key levers and potential timing. He also asked about plans to study Tumor Treating Fields in pancreatic cancer with other chemotherapy regimens.

Answer

CFO Christoph Brackmann reiterated that the company has a path to profitability, anchoring expectations to an approximate $750 million revenue level for adjusted EBITDA breakeven, and confirmed they are on track with internal plans. He also stated they are actively exploring new combinations for pancreatic cancer. CEO Ashley Cordova added that the upcoming PANOVA-4 data will help inform future directions.

Jonathan Chang's team inquired about the potential read-through from the positive PANOVA-3 results to the PANOVA-4 trial in metastatic pancreatic cancer and sought commentary on the local versus systemic effects of Tumor Treating Fields.

Answer

CEO Ashley Cordova cautioned against direct read-throughs but suggested the LUNAR trial's combination of TTFields and an immune checkpoint inhibitor (ICI) was a more interesting parallel. Executive Nicolas Leupin emphasized the significance of a positive Phase III trial in pancreatic cancer, noting PANOVA-4's combination with an ICI in metastatic disease could build on indications of systemic impact.

Jonathan Chang inquired about the specific timing and venue for the full PANOVA-3 data presentation and what additional details might be revealed compared to the top-line results.

Answer

CEO Ashley Cordova stated that while she could not yet confirm a specific conference, Novocure is targeting major medical conferences in the spring and will announce details upon acceptance. Executive Nicolas Leupin added that the company is thrilled to present these important data soon.

Jonathan Chang of Leerink Partners questioned how the upcoming executive leadership transitions might impact Novocure's overall corporate strategy. He also requested an update on the regulatory review status for Optune in lung cancer in Germany and the anticipated breadth of the label.

Answer

Incoming CEO Ashley Cordova asserted that the company's core strategy will not change, maintaining a focus on growing the GBM business, executing a successful lung cancer launch, and advancing the clinical pipeline. Retiring CEO Asaf Danziger added that there were no new updates on the German regulatory process since the prior quarter but confirmed the company still anticipates receiving a broad label similar to the one granted by the FDA.

Jonathan Chang asked about the impact of recent regulatory changes, requested color on recent FDA interactions, and inquired about how RP1's response rate translates to PFS and OS, including relevant benchmarks.

Answer

CFO Emily Hill confirmed that the BLA for RP1 received priority review and that the late-cycle meeting and manufacturing inspections with the FDA were completed without any impediments to the July 22 PDUFA date. CEO Sushil Patel addressed the clinical metrics, noting that about one-third of patients achieve durable responses, with a median duration of over 20 months and over 55% of patients alive at 3 years. He benchmarked this against the typical 12% response rate and less than 12-month median OS for other options in this setting.

Jonathan Chang asked if Mersana has settled on its two expansion dose cohorts or if others might be evaluated, and also requested more specific expectations for the upcoming ASCO presentation.

Answer

An executive, likely CEO Dr. Martin Huber, confirmed that the company plans to move forward with the two current expansion doses and does not anticipate evaluating others. He described the loading dose regimen as a viable path forward. Regarding ASCO, he was firm that to avoid violating embargo rules, he could only reiterate that the presentation will be based on the backfill and escalation data and will not include any data from the expansion cohorts.

Jonathan Chang's associate inquired about Mersana's progress in mitigating Emi-Le's side effects, specifically AST/ALT elevation and proteinuria, and how this affects confidence in maintaining dose intensity. A follow-up question asked about the mechanism of proteinuria.

Answer

CEO Dr. Martin Huber explained that AST elevation is transient and not causing significant dose delays. For proteinuria, seen at higher doses, the trial protocol was amended to include prophylactic ACE inhibitors/ARBs and allow dose reductions instead of delays for asymptomatic patients. Dr. Huber also stated the company believes the proteinuria is an off-target effect, as it has been observed with other auristatin payloads.

Jonathan Chang from Leerink Partners asked about the potential impact of regulatory changes on the business and requested key learnings from the early TECELRA launch, specifically what has performed better or worse than initial expectations.

Answer

Dennis Williams stated that despite changes at the FDA, the agency remains highly engaged on the lete-cel program. Cintia Piccina highlighted several positive surprises from the launch, including faster-than-expected treatment center onboarding, seamless biomarker testing, no payer denials, and an 'unheard of' 100% manufacturing success rate with a 27-day average turnaround time.

Jonathan Chang from Leerink Partners sought clarity on the assumptions underpinning the 2027 profitability target, asked if current cash reserves are sufficient to reach that goal, and inquired about the company's business development strategy.

Answer

CEO Adrian Rawcliffe reiterated previously announced cost reductions and new savings from pausing preclinical programs. He explicitly stated that current cash is not sufficient to reach profitability and confirmed that TD Cowen has been engaged to explore all strategic and financial options, including partnerships for non-U.S. rights and pipeline assets like PRAME and CD70, strategic combinations, and other financing transactions to bridge the company to its 2027 goal.

Gander Lee, on behalf of Jonathan Chang, inquired about the patient accrual rate for the SURPASS-3 study and how the announced cost-saving plan will impact the preclinical PRAME and CD70 programs.

Answer

CEO Adrian Rawcliffe noted that the SURPASS-3 trial was accruing reasonably well and was on track for its planned interim analysis before the decision to terminate it. He stated that data from enrolled patients will likely be released within the next 12 months. He also confirmed that the PRAME and CD70 programs will now be the key focus of the early-stage pipeline resources, with an IND planned for PRAME next year.

Jonathan Chang inquired about the current status of the IND submission for MP0712, the expected timing and nature of initial clinical data, and the strategic rationale for selecting mesothelin as a target for a Radio-DARPin.

Answer

Michael Stumpp, EVP of Projects, detailed the MP0712 timeline, noting GMP manufacturing is progressing, IND submission is planned for Q2, with the imaging study starting in Q3 and therapeutic data expected in early 2026. He explained mesothelin is a promising target due to high unmet need in ovarian cancer. CEO Patrick Amstutz added that the DARPin approach is uniquely differentiated to overcome the issue of target shedding that has challenged previous mesothelin-targeted therapies.

Jonathan Chang inquired about the progress of the IND submission for MP0712, the expected timing and nature of initial clinical data, and the strategic rationale for selecting mesothelin as a target for a Radio-DARPin.

Answer

Michael Stumpp, EVP of Projects, outlined the MP0712 timeline, stating that GMP manufacturing is progressing, FDA submissions are planned for Q2 2025, and the Phase 0 imaging study is expected to start in the second half of the year, with initial therapeutic data anticipated in early 2026. He explained that mesothelin is a strong target for ovarian cancer due to high unmet need and the DARPin's unique ability to bind a specific epitope, avoiding issues with shed mesothelin that hindered prior approaches. CEO Patrick Amstutz added that this specific targeting provides a differentiated opportunity compared to other modalities.

Jonathan Chang asked for the rationale behind developing lorigerlimab in ovarian and clear cell gynecologic cancers and inquired about the timeline for initial clinical data from the MGC026 program.

Answer

Dr. Stephen Eck, SVP, Clinical Development and Chief Medical Officer, stated that initial MGC026 data would likely be available in the latter half of 2026. He explained that the company is targeting ovarian and clear cell gynecologic cancers because they are areas of high unmet need where existing checkpoint inhibitors have had limited success. Dr. Eck highlighted lorigerlimab's differentiated mechanism of targeting T-cells co-expressing PD-1 and CTLA-4 within the tumor microenvironment. Dr. Scott Koenig, President and CEO, added that the encouraging data from prostate cancer, another 'cold' tumor, supports exploring lorigerlimab in ovarian cancer.

Jonathan Chang of Leerink Partners inquired about the CEO search process and its timeline, and also asked when investors could expect initial clinical data from the MGC026 Phase I dose escalation study.

Answer

Dr. Scott Koenig, President and CEO, explained that a Board subgroup has initiated the CEO search with an outside firm, and he will remain until a successor is chosen to ensure a smooth transition. Regarding MGC026, he stated the dose escalation study is progressing well and expects to complete the study and report data in 2025.

Jonathan Chang of Leerink Partners sought to understand the evolution of vobra duo's tolerability profile versus a prior abstract, asking about time dependency of adverse events and requesting more details on the reported patient deaths.

Answer

Dr. Scott Koenig, President and CEO, clarified that the safety data continues to accumulate but remains manageable. He stated that the cardiac-related deaths were deemed unrelated to the treatment. The two cases of pneumonitis and one death following a pleural effusion were still under investigation, noting one pneumonitis case had confounding medical factors.

Jonathan Chang from Leerink Partners asked about the company's perspective on business development opportunities for 2025.

Answer

Travis Coy, CFO and Head of Corporate Development, responded that while the company is very excited about its internal pipeline, it continuously evaluates external opportunities that offer a good strategic fit and leverage its expertise. He emphasized that Immunocore's strong position provides the optionality to pursue partnerships.

Jonathan Chang of Leerink Partners asked about the evolving competitive landscape for uveal melanoma and requested more details on how the company's AI-enabled patient finder tool works.

Answer

David Berman, Head of R&D, expressed confidence in KIMMTRAK's 3-year survival data and its well-designed adjuvant trial. Ralph Torbay, Head of Commercial, explained the AI tool uses predictive models to identify patients in low-density community centers, enabling a 'just-in-time' commercial approach without increasing the sales force.

Asked about the evolving competitive landscape for uveal melanoma and for more details on the AI patient-finding tool.

Answer

The company is confident in KIMMTRAK's position due to its established survival benefit and well-designed trials for expansion. The AI tool helps efficiently find patients in low-density community settings by predicting their appearance, optimizing the sales force.

Jonathan Chang of Leerink Securities asked about the evolving competitive landscape in uveal melanoma and requested more details on the company's AI-enabled patient finder tool.

Answer

David Berman, Head of R&D, addressed competition by highlighting KIMMTRAK's 3-year survival data and the well-designed ATOM trial in the adjuvant setting. Ralph Torbay, Head of Commercial, explained the AI tool uses predictive models to identify patients in low-density community practices, enabling 'just-in-time' rep deployment without increasing the field force footprint.

An analyst, identified as Jonathan, inquired about Nanobiotix's strategies to extend its cash runway and asked for details on the strategic alignment process with Johnson & Johnson for the NBTXR3 global development plan, including the timeline for medium- to long-term opportunities.

Answer

Co-Founder and CEO Laurent Levy explained the strategic decision to transfer sponsorship of the NANORAY-312 trial to Janssen (a Johnson & Johnson company) sooner rather than later. He stated this move de-risks the path to market and shifts focus from a rapid interim readout to a broader, more secure global launch strategy. CFO Bart Van Rhijn addressed the finances, reaffirming the cash runway into Q3 2025 and expressing confidence in securing additional financing through the updated timeline, supported by upcoming data milestones and multiple available options.

Jonathan Chang of Morgan Stanley inquired about the driver behind a EUR 10 million gain on net indebtedness, the amount of CapEx spent on decarbonization, and the key factors for the Q2 free cash flow outlook.

Answer

CFO Alexandre Blum explained the gain resulted from the revaluation of shares held for long-term incentive plans. CEO Philippe Kehren stated that decarbonization CapEx is part of the essential CapEx budget, with about EUR 30 million planned for 2024. Blum reiterated that Q2 free cash flow is expected to be only slightly positive due to variable remuneration and tax payments.