John Newman

John Newman inquired about the timing of the CHOPIN study publication and Delcath Systems' strategy for leveraging this data in the United States, including when its commercial impact might be observed. He also asked about the company's prioritization between accelerating enrollment in the metastatic colorectal cancer (MCRC) and metastatic breast cancer (MBC) clinical studies and maintaining a cash flow positive status for the business.

Answer

Gerard Michel, CEO, stated that the CHOPIN publication is 'imminent,' likely within the next month, and will be utilized by sales representatives, Medical Science Liaisons, and senior medical staff. He also highlighted its potential to support updates to NCCN guidelines, emphasizing HEPZATO's role and the safe use of combination therapy. Regarding prioritization, Michel explained that with over $90 million in cash and investments, the company prioritizes long-term value creation through clinical development, even if it means experiencing cash flow negative quarters, rather than focusing on short-term cash flow positivity.

John Newman inquired about the anticipated publication timeline for the CHOPIN study data and Delcath's strategy for leveraging these results in the United States. He also asked how Delcath balances the rapid enrollment and progression of its metastatic colorectal cancer (MCRC) and metastatic breast cancer (MBC) clinical studies with the goal of maintaining positive cash flow for the business.

Answer

Gerard Michel, CEO, indicated that the CHOPIN study publication is expected within approximately one month. He outlined a multi-faceted utilization strategy involving sales representatives, Medical Science Liaisons (MSLs), and senior medical staff to educate physicians and support potential updates to NCCN guidelines, emphasizing HEPZATO KIT's role and the combination therapy with ipilimumab/nivolumab. Regarding clinical development versus cash flow, Mr. Michel stated that with a healthy balance sheet of over $90 million, the company prioritizes long-term value creation over quarter-to-quarter cash flow positivity, acknowledging that some quarters may be cash flow negative.

John Newman of Canaccord Genuity Inc. asked for a long-term perspective on the NDRA program, questioning why the 340B pricing is attractive to hospitals and its potential to expand treatment volume over time.

Answer

CEO Gerard Michel explained that while the net effect is a 10-15% reduction in average revenue per kit in Q3, the program makes the product more attractive to hospitals on a portfolio basis. He believes this will lead to increased volume over time by removing a potential financial barrier for certain patients, although this effect is difficult to quantify.

John Newman of Canaccord Genuity inquired about the average number of HEPZATO treatment cycles per patient at newly activated U.S. centers and whether this figure is evolving as centers gain more experience with the procedure.

Answer

CEO Gerard Michel stated that while it's too early for a definitive trend, the average number of treatment cycles appears to be tracking consistently with the 4.1 cycles observed in the FOCUS trial. He expressed optimism for a potential increase due to strong product tolerability and anecdotal efficacy but emphasized it's premature to confirm.

John Newman from Canaccord Genuity inquired about the specific types of data expected from the CHOPIN trial in 2025 and asked about the projected timelines for patient enrollment in the upcoming colorectal and breast cancer trials.

Answer

CMO Vojo Vukovic explained that the 76-patient randomized CHOPIN trial is fully enrolled, with a data readout anticipated in mid-2025 and a public presentation in the second half of 2025. For the new Phase II trials, he projected that patient enrollment for the colorectal cancer study would begin in mid-2025, followed by the breast cancer study in Q4 2025. Each 90-patient trial is expected to take approximately two years to enroll.

John Newman asked about the clinical approach to tapering immunosuppressants in the autoimmune trial and the advantages an allogeneic therapy offers in this setting.

Answer

EVP of R&D and CMO Dr. Zachary Roberts highlighted this as a key advantage of an off-the-shelf therapy. He explained that ALLO-329 allows patients to remain on immunosuppressants until just before infusion, minimizing care disruption compared to autologous therapies that require two separate tapering periods. This logistical benefit is a key differentiator with clinical sites.

John Newman from Canaccord Genuity asked about the expected follow-up duration for the initial ALLO-329 data by year-end 2025 and whether the trial design allows for measuring the depletion of activated T-cells.

Answer

Dr. Zachary Roberts, EVP of R&D and CMO, said they expect enough follow-up on a handful of patients for biomarker proof-of-concept (cell expansion, B-cell depletion) but not durable efficacy. He confirmed they will measure T-cell depletion, using similar analyses from the ALLO-316 program to validate the Dagger effect.

John Newman asked about the scientific rationale and importance of targeting both B cells and T cells with ALLO-329 in autoimmune disease, given that much of the industry focus has been solely on B-cell depletion.

Answer

Dr. David Chang, President and CEO, explained that T cells are a key contributor to B-cell maturation and pathology. By targeting both, ALLO-329 may address the underlying disease more fully. He emphasized that the CD70 target also incorporates the Dagger technology, which is critical to the strategy of enabling treatment with minimal or no lymphodepleting chemotherapy, a key differentiator for the program.

John Newman asked a financial question regarding whether there was any impact from Medicaid reserve adjustments during the first quarter.

Answer

CFO Peter Pfreundschuh responded that the company is now seeing stabilization in its Medicaid and 340B gross-to-net calculations. He clarified that unlike the significant adjustments seen in 2024, Y-mAbs does not anticipate major changes to these reserves going forward in 2025.

John Newman of Canaccord Genuity asked about the commercial performance of DANYELZA, specifically whether the duration of therapy continues to mature in the U.S. and if this could be a meaningful driver of future growth.

Answer

Chief Commercial Officer Sue Smith confirmed that the company is seeing an increase in the duration of therapy. She also noted that a new marketing campaign, which highlights DANYELZA's efficacy in patients who have been on a prior GD2 therapy, is successfully increasing uptake among physicians for patients with bone or bone marrow involvement.

John Newman inquired about the potential follow-up duration the FDA might require for the primary endpoint in the SER-155 Phase 2 study, and whether the trial is designed to assess overall survival as an endpoint.

Answer

President and CEO Eric Shaff noted that the study design incorporates prior FDA feedback. Dr. Dennis Walling, SVP of Clinical Development, confirmed the intended primary endpoint is the reduction of bloodstream infections, consistent with the Breakthrough Therapy Designation. Chief Scientific Officer Dr. Matthew Henn added that while the protocol is being finalized, the study is designed to be 'data rich' and will collect data to look for signals related to survivability, given known associations from other cohort studies.

John Newman from Canaccord Genuity asked about the potential size of the next clinical study for SER-155, assuming a Phase II trial. He also inquired about other potential efficacy endpoints that could be evaluated in addition to the primary endpoint of bloodstream infection reduction, such as acute Graft-versus-Host Disease (GvHD).

Answer

Eric Shaff, President and CEO, highlighted that a standalone Phase II study could provide an interim data readout within 12 months of initiation, which would be valuable for informing the path forward. Lisa von Moltke, CMO, mentioned that other endpoints would include febrile neutropenia, antibiotic use, and hospitalization rates. She noted that while GvHD would be tracked for safety, the low incidence rates observed in their Phase I study make it an unlikely efficacy endpoint. Eric Shaff also added that interim results could help inform expansion into adjacent patient populations.

John Newman asked for BioNTech's thoughts on recent FDA comments about potentially requiring a randomized study for future COVID-19 vaccine strain updates and whether this is a feasible or likely scenario.

Answer

Chief Strategy Officer Ryan Richardson responded by noting the vaccine's initial approval was based on a large 43,000-participant randomized study. He stated that they do not expect this discussion to have a near-term impact on the franchise, as their immediate focus is on the upcoming strain selection process for the fall 2025 season.

John Newman from Canaccord Genuity asked for specifics on the prior antibody-drug conjugate (ADC) treatments for patients expected to enroll in the breast cancer study and questioned the trial's geographical scope.

Answer

Chief Medical Officer Dr. Tom Heineman responded that while the treatment landscape is dynamic, it is reasonable to assume the majority of patients will have previously failed an ADC, most likely ENHERTU, based on current data. He also stated that the study is anticipated to have substantial enrollment in North America, with the company currently evaluating other geographies, including major Western European countries.

John Newman from Canaccord Genuity Group Inc. inquired about the potential design of the upcoming pivotal study for pelareorep in metastatic breast cancer, ahead of the company's meeting with the FDA.

Answer

Chief Medical Officer Dr. Thomas Heineman, with input from CEO Dr. Matt Coffey, explained that the company will discuss the study's key elements, including the patient population, primary endpoint, and statistical plan, with the FDA in Q2 2024. Dr. Heineman noted the design must account for the evolving standard of care, referencing recent DESTINY-Breast06 results, with the goal of creating an efficient and flexible trial that could potentially lead to an early registration filing.

Inquired about the additional clinical data for tab-cel that will be included in the 2024 BLA filing and the company's commercial plans for ATA188, specifically regarding potential partnerships.

Answer

A new data cut from the pivotal ALLELE study from October will be included in the BLA submission, and the company is confident in the data based on historical consistency. For ATA188, if results support moving to Phase III, the plan is to seek a strategic partner for a co-development program to manage the large clinical studies, while retaining significant value for Atara, possibly through a profit-split in the U.S.

John Newman from Canaccord Genuity questioned Selecta's long-term strategy for its unique, tax-optimized royalty stream from the SEL-212 partnership with Sobi, asking whether the company intends to retain or monetize it.

Answer

Executive Blaine Davis confirmed the royalty stream is tax-optimized up to approximately $400 million. However, he stated that no final decision has been made on whether to retain or monetize this asset, emphasizing that the primary goal is to maximize long-term stockholder value.

John Newman posed two questions: first, he asked for clarification on the future expenses Selecta will be responsible for regarding the SEL-212 program with Sobi. Second, he inquired about the expected timeline for the ImmTOR IL program to enter clinical trials.

Answer

CFO Blaine Davis responded that under the agreement with Sobi, all expenses related to the BLA preparation, completion of clinical activities, and ImmTOR manufacturing will be reimbursed by Sobi. CEO Carsten Brunn addressed the second question, stating that while an exact clinical entry timeline for ImmTOR IL is not yet being provided, the company is on track to initiate IND-enabling studies for the program in 2023.

John Newman asked for clarification on Selecta's future financial responsibilities for the SEL-212 program with Sobi and requested a timeline for the ImmTOR IL program's entry into the clinic.

Answer

CFO Blaine Davis stated that all expenses related to the SEL-212 BLA preparation, trial completion, and ImmTOR manufacturing are reimbursed by Sobi. CEO Carsten Brunn said that while an exact clinical timeline for ImmTOR IL is not yet set, the company is on track to begin IND-enabling studies in 2023 and has made it a top priority.

John Newman asked about the future expenses Selecta is responsible for regarding SEL-212 under the Sobi partnership and requested a timeline for the ImmTOR IL program to enter the clinic.

Answer

CFO Blaine Davis clarified that the agreement with Sobi provides for reimbursement of all expenses related to the BLA preparation, clinical trial completion, and ImmTOR manufacturing. CEO Carsten Brunn stated that while an exact clinical entry timeline for ImmTOR IL is not yet set, the company is on track to initiate IND-enabling studies in 2023.

John Newman from Canaccord Genuity inquired about Selecta's future expense responsibilities for the SEL-212 program with Sobi and the projected timeline for the ImmTOR IL program to enter clinical trials.

Answer

CFO Blaine Davis stated that under the agreement with Sobi, all costs for BLA preparation, clinical trial completion, and ImmTOR manufacturing are reimbursed by Sobi. CEO Carsten Brunn noted that while a specific clinical entry date for ImmTOR IL is not yet set, the company is on track to begin IND-enabling studies in 2023.

John Newman of Canaccord Genuity asked about the level of detail that will be shared in the top-line data for SEL-212, specifically regarding safety and the incidence of gout flares.

Answer

President and CEO Carsten Brunn reiterated that the company remains blinded to the data. Chief Medical Officer Peter Traber clarified that while early trials suggested a reduction in gout flares, the larger COMPARE trial did not show a significant difference. He stated that the DISSOLVE trials will provide the best comparison against placebo, and the company will be able to report on the number of gout flares versus placebo.

John Newman of Canaccord Genuity asked about the level of detail that will be provided on safety, specifically regarding the incidence of gout flares, in the upcoming top-line data for the SEL-212 DISSOLVE trials.

Answer

President and CEO Carsten Brunn noted the company remains blinded to the data. Chief Medical Officer Peter Traber clarified that while uricase therapies typically increase gout flares, the DISSOLVE trials will provide the best comparison against a placebo arm. He stated that they will have data on the number of gout flares over different time periods versus placebo and will be able to report on it in the top-line readout.

John Newman from Canaccord asked for a review of the ImmTOR dosing strategy planned for the upcoming gene therapy study in methylmalonic acidemia (MMA).

Answer

Chief Medical Officer Peter Traber detailed the plan, which is based on prior empty capsid and non-human primate studies. The regimen will start with three monthly doses of ImmTOR at 0.5 mg/kg following the AAV gene therapy. He added that the protocol allows for a dose increase if needed based on early patient data.