Reni Benjamin

Reni Benjamin asked for confirmation on the timing of the BTK degrader's accelerated approval, noting a perceived pushout from the first half to the second half of the year, and requested reasons for any delay.

Answer

Amit Aggarwal, Chief Medical Officer of Hematology, clarified that there has been no change in the timing for the BTK degrader's accelerated approval, with FDA interactions and filing based on single-arm trial data still expected mid-year.

Reni Benjamin questioned the timing of the BTK degrader's accelerated approval, seeking clarification on a perceived pushout from the first half to the second half of the year.

Answer

Amit Aggarwal, Chief Medical Officer of Hematology, confirmed there has been no change in the timing for the BTK degrader's accelerated approval. He stated they are following single-arm trial data and anticipate interactions with the FDA mid-year for filing, with no pushout.

Reni Benjamin asked management to highlight the most exciting of the ten anticipated proof-of-concept readouts for the year. He also requested an overview and expectations for the interim analysis of the Phase III MANGROVE trial for BRUKINSA.

Answer

Wang Lai, Global Head of R&D, expressed excitement for all upcoming readouts, declining to name a favorite, and noted that data is expected this year for most molecules that entered the clinic last year. Regarding the MANGROVE study, he stated it is an event-driven trial and the company hopes the required events for the interim analysis will occur in the second half of 2025.

Reni Benjamin from Citizens JMP inquired about the recently completed enrollment of the CELESTIAL study, asking for expectations on event rates and a potential timeline for top-line data and NDA submission.

Answer

CEO John Oyler celebrated the rapid 14-month enrollment as proof of strong execution. He clarified that the study is event-driven with a PFS endpoint and did not provide a specific timeline, noting that the active control arm (venetoclax + obinutuzumab) means it will take time for sufficient events to accrue.

Reni Benjamin asked about the recently completed enrollment for the CELESTIAL study, inquiring about expectations for event rates and a potential timeline for top-line data and an NDA submission.

Answer

CEO John Oyler celebrated the rapid 14-month enrollment as proof of strong clinical execution. However, he did not provide a specific timeline for the readout, explaining that the study is event-driven with a PFS endpoint and will take time to mature, given the active control arm.

Reni Benjamin from Citizens JMP asked about the recently completed enrollment of the CELESTIAL study and sought details on expected event rates, the timeline for top-line data, and a potential NDA submission.

Answer

CEO John Oyler highlighted the rapid 14-month enrollment as a demonstration of strong clinical execution. He confirmed the study is event-driven with a PFS endpoint but did not provide a specific timeline for the data readout, noting that the control arm's data will take time to mature.

Reni Benjamin asked about the drivers of Q4 acceleration, specifically the contribution from new community ATCs versus existing academic centers, and the expected growth trajectory for community ATCs in 2026. He also inquired about the timing and details of the sarcoma data presentation, including depth and durability of response, and the anticipated size of the registrational study.

Answer

Dan Kirby, Chief Commercial Officer, stated Q4 growth was significant in academic ATCs, with new community ATCs coming online with an expected learning curve. Academic ATCs saw growth from accessing previously untreated patient types through earlier procurement strategies. Frederick Vogt, Interim CEO and President, expects sarcoma data presentation at a medical congress (ASCO/ESMO) this year. Brian Gastman, EVP of Transitional Medicine and Research, highlighted deep and improving responses over time, similar to melanoma and NSCLC. An unnamed company representative indicated registrational study sizes for similar sarcoma subtypes ranged from 30-60 patients, predominantly around 40.

Reni Benjamin asked about the drivers of Q4 acceleration (new community ATCs vs. existing academic centers), the expected growth trajectory for community ATCs in 2026, the timing and conference for full sarcoma data presentation, details on the depth and durability of response in sarcoma patients, and the anticipated size of the registrational study for this rare disease.

Answer

Dan Kirby, Chief Commercial Officer, explained that Q4 growth was significant in academic ATCs, with new community ATCs coming online and expected to ramp up after a learning curve and financial reimbursement confirmation. Frederick Vogt, Interim CEO and President, stated that sarcoma data would be presented at a medical congress this year (ASCO/ESMO likely). Brian Gastman, EVP of Transitional Medicine and Research, described responses as deepening over time, similar to melanoma and lung cancer, indicating long durability. For the registrational study, Brian Gastman mentioned that based on prior FDA approvals for soft tissue sarcoma, the study size is expected to be similar, predominantly in the 40-patient range.

Reni Benjamin from Citizens Capital Markets asked for specific details on the improvement in patient drop-off and manufacturing out-of-spec rates from Q1 to Q2, and how the new McKesson specialty pharmacy agreement is expected to impact revenues.

Answer

COO Igor Bilinsky confirmed that manufacturing success rates rebounded in Q2, with lower drop-offs and out-of-spec rates, reflected by a decrease in scrap costs noted in the quarterly filing. CCO Dan Kirby added that the specialty pharmacy channel could have a significant long-term impact by providing access to healthier patients earlier and opening up hospital networks that were previously constrained by direct purchasing costs.

Reni Benjamin of Citizens JMP inquired about strategies to standardize procedures across ATCs to improve manufacturing outcomes and questioned the rationale for issuing 2025 guidance early in 2024, which has now been revised.

Answer

EVP of Medical Affairs Dr. Brian Gastman described a 'white glove service' where field teams work directly with new surgeons to accelerate the learning curve. Interim CEO Frederick Vogt explained the initial guidance was based on a maximum manufacturing ramp-up, but has now been revised to more accurately reflect the observed ATC adoption timelines and referral patterns, which also aligns cash spend.

Reni Benjamin requested management to set expectations for upcoming data in non-small cell lung cancer (NSCLC) and endometrial cancer, asking about patient numbers and whether the data would be registrational.

Answer

Chief Medical Officer Dr. Friedrich Graf Finckenstein stated that for NSCLC (IOV-LUN-202), the company will provide an update on the registrational cohorts, with a regulatory decision anticipated by the end of 2027. For endometrial cancer (IOV-END-201), an initial, meaningful data set will be shared in the second half of the year to show early signals, without committing to specific patient numbers for either trial at this time.

Reni Benjamin commented on the HARMONi-6 safety profile, asking if there were any squamous-specific adverse events different from the non-squamous cohort in HARMONi, and how Summit Therapeutics is addressing the perceived underappreciation for ivonescimab's safety, especially regarding bleeding, with KOLs. He also asked if the HARMONi filing would go to ODAC, if they are seeking accelerated or full approval, and for thoughts on European filings.

Answer

Jack West, VP of Clinical Development, explained that squamous tumors tend to be larger and more central, and brain metastases are less common than in adenocarcinoma. He emphasized that ivonescimab's safety profile differentiates it from bevacizumab, requiring education and gradual experience for oncologists. Urte Gayko, Chief Regulatory Quality and Safety Officer, stated that it is a solid package for full approval, but could not foresee ODAC involvement or specific European filing details.

Reni Benjamin asked whether the PFS and OS endpoints in the HARMONi study are being evaluated as co-primary or dual endpoints. He also inquired about the company's strategy to mitigate potential geopolitical risks related to manufacturing, tariffs, and intellectual property.

Answer

Executive Dave Gancarz clarified that the HARMONi trial uses dual primary endpoints, tested hierarchically with PFS first, then OS. COO and CFO Manmeet Soni addressed geopolitical concerns, stating that the company is mitigating manufacturing risk by transferring know-how to third-party contract manufacturers in the U.S. and Europe, in addition to its supply from Akeso. He also affirmed that the company's intellectual property for ivonescimab is secure into the late 2030s.

Reni Benjamin asked whether HARMONi's PFS and OS are co-primary or dual endpoints and raised concerns about geopolitical tensions impacting manufacturing, IP, and API supply from China.

Answer

Executive Dave Gancarz clarified they are dual primary endpoints with hierarchical testing. COO & CFO Manmeet Soni addressed geopolitical concerns, stating that Summit is mitigating risk by transferring know-how to third-party contract manufacturers in their licensed territories, in addition to their supply from Akeso. He also confirmed their IP is secure into the late 2030s and that adding new CMOs would follow standard regulatory filing processes.

Reni Benjamin of Citizens JMP asked about Summit's next solid tumor indications for investment, the timing of updated data from ongoing studies, and whether their strategy follows Akeso's lead or branches out independently. He also inquired about the expected number of global sites for HARMONi-7.

Answer

An executive explained their strategy is multifaceted, leveraging Akeso's Phase II data, branching out via their MD Anderson collaboration and IST program, and running their own studies. Manmeet Soni, COO & CFO, highlighted a new Phase II colorectal cancer study with Akeso that Summit is now activating. Regarding HARMONi-7, Mr. Soni stated that while specific numbers are not provided, they expect most sites to be activated by the end of 2025.

Reni Benjamin of Citizens Capital Markets asked for the rationale behind using a cyclophosphamide-only regimen for ALLO-329 in autoimmune disease and what proof-of-concept data would be needed for a go/no-go decision.

Answer

CEO Dr. David Chang explained the choice was driven by a better benefit-risk profile, as removing fludarabine improves safety and cyclophosphamide is familiar to rheumatologists. For proof-of-concept, he cited key biomarkers like the degree of B-cell depletion, phenotype of returning B-cells, and disappearance of autoantibodies, which would precede ultimate clinical response data.

Reni Benjamin asked for the total number of expected ALPHA3 trial sites globally, the estimated number of patients needed for screening to achieve full enrollment, and details on how investigators are discussing the trial with patients.

Answer

EVP of R&D and CMO Dr. Zachary Roberts stated the North American target is around 50 sites, with global expansion details to follow. He confirmed the model assumes roughly 1 in 5 screened patients will be MRD positive. He also explained that investigator communication has improved by introducing the trial early in the treatment process, which has enhanced patient consent rates.

Reni Benjamin asked management to highlight the most exciting of the ten anticipated proof-of-concept readouts for the year. He also requested an overview and expectations for the interim analysis of the Phase III MANGROVE trial for BRUKINSA.

Answer

Lai Wang, Global Head of R&D, declined to name a favorite among the upcoming proof-of-concept readouts, stating his excitement for all of them. Regarding the MANGROVE trial, he explained it is an event-driven study and the company hopes the interim analysis will occur in the second half of the year.

Reni Benjamin asked management to highlight the most exciting of the ten anticipated proof-of-concept readouts for the year. He also requested an overview and expectations for the interim analysis of the Phase III MANGROVE trial.

Answer

Lai Wang, Global Head of R&D, expressed excitement for all upcoming readouts, noting that most molecules that entered the clinic last year should yield data this year. Regarding the MANGROVE trial, he stated it is an event-driven study and that the company hopes the interim analysis will occur in the second half of 2025.

Reni Benjamin asked for details on the tumor regressions in the EpCAM program, including patient time on therapy and any observed toxicities. He also questioned how the Mec-V landmark survival data compares to the competitive landscape, the ideal structure for a partnership deal, and which two programs the company is focusing on internally.

Answer

Executive Eric Sievers reported that in the EpCAM program, two colorectal cancer patients had extended progression-free intervals (one over a year), but no formal RECIST responses have been observed yet, and the safety profile is not concerning. CEO Jay Short and Eric Sievers emphasized that Mec-V's overall survival data is exceptional compared to standard of care, even in more heavily pretreated patients. Regarding strategy, Jay Short clarified that the internal focus is on the EpCAM and Mec-V programs, while ROR2 and CTLA-4 are prioritized for partnerships. He described an ideal partnership scenario involving one deal that retains North American value and another that generates significant upfront cash.

Sam, on behalf of Reni Benjamin from Citizens JMP, questioned if there were ongoing partnership discussions for the BA-3182 asset and whether these talks were contingent on the mid-2025 data readout.

Answer

Executive Sheri Lydick confirmed that while there has been interest in the BA-3182 program, the company's goal is to complete the Phase 1 dose escalation and expansion cohorts first. She stated they would not seriously engage in partnership discussions until they have a robust data set to drive value for the program.

Asked about the key reasons for discontinuing luvelta, the learnings to be applied to STRO-004, and for more specific guidance on the expected reduction in R&D and SG&A expenses following the restructuring.

Answer

The luvelta decision was purely financial due to the high capital required for late-stage development, not due to clinical data, which remains encouraging. The key learning applied to STRO-004 is to focus on a clearly differentiated profile and commercial viability. While a dramatic decrease in spending is expected after Q1 2025, specific guidance was not provided, but they noted 2024 spend was ~$300M (mostly luvelta) and there will be ~$40-45M in 2025 restructuring charges.

Reni Benjamin from Citizens Bank questioned the primary rationale for discontinuing luvelta, the key learnings being applied to the STRO-004 program, and sought more specific guidance on the magnitude of expected operating expense reductions.

Answer

Executive Jane Chung stated the luvelta decision was driven by the significant capital required for late-stage development, not by clinical findings, and that the key learning is to strategically focus on highly differentiated assets. CFO Ed Albini added that from a 2023 expenditure base of ~$300 million (mostly luvelta-related), a 'dramatic decrease' in spending is expected for the remainder of 2024 and beyond, after accounting for Q1 luvelta costs and restructuring charges.

Asked about the expected ex-U.S. contribution to the 2030 and peak revenue targets, and inquired about the potential for interim data from the HARBOR study and the timeline for the Phase 3 readout.

Answer

The company expects the U.S. to remain the primary revenue driver, likely representing 70-75% of sales in 2030. Regarding the HARBOR study for elenestinib, it is still in the early stages of site activation, and the company will provide updates on timelines and potential data readouts at a later date.

Inquired about the prescriber base, asking how many of the top targeted physicians are prescribing, if the goal is for them to reach 10+ patients each, and if the strategy includes expanding beyond this initial group.

Answer

Prescriber adoption is broad and extends well beyond the initial 400-450 targeted physicians. The company is seeing a 'deepening' trend where experienced prescribers are treating more patients (some over 10), and this is happening across all specialties (hematology, oncology, allergy) and settings (academic, community), not just within the top group.

Reni Benjamin of JMP Securities asked about the potential filing timeline for povorcitinib in hidradenitis suppurativa (HS) after the Phase III data, its use relative to other therapies, and its ultimate market share potential.

Answer

Steven Stein, an executive, confirmed that as a first filing, it will require a comprehensive safety database and reiterated the guidance for a potential 2026 approval. He stated that market positioning against other orals or biologics will depend on the final Phase III efficacy profile. He noted the addressable moderate-to-severe patient population seeking therapy is between 150,000 and 300,000.

Reni Benjamin of Citizens JMP asked for context on CUE-101's results given the competitive landscape, an update on the neoadjuvant study, and clarification on the company's funding strategy to bridge to potential ONO milestone payments.

Answer

CMO Dr. Matteo Levisetti highlighted CUE-101's superior 12-month survival rate (90%) compared to historical data and noted competitor data is still preliminary. He also confirmed the neoadjuvant study is nearing enrollment completion. Executive Daniel Passeri detailed the funding strategy, which relies on a reduced cash burn and securing non-dilutive capital through a CUE-501 partnership to supplement future milestones from the ONO collaboration, thereby extending the cash runway.

Asked for details on the upcoming ASCO data for CUE-101 and CUE-102, the company's strategic thinking on partnering the oncology assets to fund the autoimmune programs, the mechanism of action for the CUE-500 series, and when preclinical data for it might be presented.

Answer

At ASCO, CUE-101 will have an oral presentation with longer follow-up, and CUE-102 will be a poster with data on ~35+ patients. The company acknowledged the strategic consideration of monetizing oncology assets to fund the high-interest autoimmune pipeline. The CUE-500 mechanism redirects pre-existing antiviral T cells to kill B cells via CD19 targeting. Preclinical data is expected to be presented in H2 2024 or early 2025.

Asked about the CUE-101 patient who achieved a late partial response, the durability and progression-free survival (PFS) for low CPS patients in the combination study, details on the neoadjuvant trial, and potential future combinations for the CUE-102 program.

Answer

The patient with the late partial response completed 24 months of therapy, with a reduced dosing schedule after about a year. For the low CPS combination study, durability and PFS are still maturing but are favorable compared to historical data, with PFS currently at nearly 6 months. The neoadjuvant trial shows encouraging preliminary data, including expansion of T cell clonality and NK cells in the tumor microenvironment. For CUE-102, potential combinations are being considered and will depend on the tumor type, possibly including checkpoint inhibitors or chemotherapy.

Reni Benjamin from H C Wainwright asked for details on the upcoming interim analysis for the fosbretabulin GI-NET study, the potential for a combination trial, highlights from the AACR program, the status of the ovarian cancer program, and the projected cash burn rate.

Answer

President & CEO David Chaplin stated the GI-NET interim analysis will assess biomarker reduction, symptom control, and quality of life. He confirmed the potential for a future combination study. Regarding the AACR program, he highlighted emerging data on angiogenesis and bone metastasis. For ovarian cancer, he noted the company awaits FDA feedback on a Phase 3 trial design by the end of Q2. CFO Barbara Riching projected the monthly cash burn would increase slightly from $1.2 million to about $1.3 million to support the new AML trial.

Reni Benjamin from H.C. Wainwright asked about the expected timing for the overall survival (OS) data from the GOG study and sought insights on the potential design of the subsequent Phase 3 trial, specifically regarding a non-inferiority versus a superiority study. He also inquired about any upcoming data updates for OXi4503 at conferences like AACR.

Answer

CEO Dave Chaplin estimated the GOG OS data would likely be available late 2015 or early 2016. Regarding trial design, he stated a superiority study is preferred, but the final approach depends on FDA feedback. For OXi4503, Chaplin anticipated an update at the ASH conference in December, not at AACR, and mentioned a publication on preclinical data was also in preparation.