Boobalan Pachaiyappan

Boobalan Pachaiyappan inquired about the progress of potential U.S. partnership discussions, whether these partners might also have ex-U.S. presence, and key factors for finalizing a partnership post-NDA filing. He also asked if the FDA's view on the SHIELD II study design aligned with positive KOL feedback and about the projected D-PLEX100 formulary inclusion rate within integrated delivery networks (IDNs) in the first 12 months post-approval.

Answer

CEO Dikla Czaczkes Akselbrad confirmed the primary focus is on U.S. partnerships, with potential for other geographies. She and COO Ori Warshavsky emphasized that ideal partners possess broad hospital-based capabilities and a strong presence in the surgical suite. Ms. Akselbrad stated that positive FDA feedback, including confirmation of the NDA pathway and sufficiency of clinical data, indicated alignment with positive views on the SHIELD II study. Mr. Warshavsky explained that formulary uptake would be a gradual, hospital-by-hospital process, dependent on the partner's efforts in educating surgeons, P&T reviews, and potential pilot studies, but noted that once on formulary, usage tends to be sticky and grow steadily.

Boobalan Pachaiyappan asked about the progress in U.S. partnership discussions, specifically if the potential partner would also have an ex-U.S. presence and what factors would be pivotal in closing the partnership post-NDA filing. He also questioned if the FDA shared Dr. Wexner's positive view on the SHIELD II study design and patient characteristics during the pre-NDA meeting. Finally, he inquired about the expected percentage of target IDNs likely to include D-PLEX100 on formulary within the first 12 months post-approval.

Answer

CEO Dikla Czaczkes Akselbrad stated that PolyPid is currently focused on U.S. partnerships as the highest priority, though ex-U.S. interest might arise. COO Ori Warshavsky added that the ideal partner possesses broad hospital-based capabilities and a strong presence in the surgical suite, and due diligence is becoming increasingly detailed. Ms. Akselbrad confirmed that the FDA's positive feedback, including confirmation of the NDA pathway and sufficiency of clinical data, indicated alignment with the positive view on SHIELD II. Mr. Warshavsky explained that formulary uptake would be a mission for the U.S. commercial partner, involving steps like identifying champions, P&T review, potential pilot studies, and electronic system updates. He noted that uptake would take time but, once on formulary, the product tends to be sticky with steadily growing usage.

Asked for details on the SHIELD II top-line data reporting, trial success criteria, commercial manufacturing readiness and capacity, and context for the recent increase in SSI rates.

Answer

The company will report the primary composite endpoint (SSI, mortality, reintervention) and key secondary endpoints. Trial success is based on achieving statistical significance (alpha < 0.05). Inspection readiness is a top priority involving mock inspections and consultants. Manufacturing capacity is deemed sufficient for the first 4-5 years of launch. The recent SSI data shows a 3% increase in 2023 vs 2022, the first uptick since a drop during the COVID years.

Boobalan Pachaiyappan asked about the viability of the HLHS BLA filing given the potential sunsetting of the PRV program, the impact of FDA leadership changes, the availability of six-year survival data from the HLHS Phase 1 trial, the rationale for using a CDMO for manufacturing, and the basis for the FDA's confidence in allowing a pivotal Phase 2 trial for pediatric DCM.

Answer

CEO Wa'el Hashad expressed cautious optimism about the PRV program's reauthorization but noted that Fast Track designation also allows for a rolling submission. He affirmed confidence in the FDA's commitment based on multiple recent collaborative meetings. Chief Medical Officer Nataliya Agafonova clarified the Phase 1 study's follow-up was set at five years. CTO Devin Blass detailed that using a CDMO is faster, more cost-effective, and lower risk. Multiple executives, including Dr. Agafonova and CSO Dr. Joshua Hare, attributed the FDA's confidence in the DCM program to the robust trial design, meaningful endpoints, and the therapy's strong existing safety profile.

Boobalan Pachaiyappan of ROTH Capital Partners asked if the fantastic 100% survival in the ELPIS I long-term follow-up included additional cardiac parameters that might predict ELPIS II success. He also inquired about the efficacy benchmark for the RVEF endpoint in ELPIS II and the competitive landscape, specifically mentioning VentriGel.

Answer

Nataliya Agafonova (executive) explained that while the ELPIS I follow-up initially only tracked survival, the company is now working to retrospectively collect more granular cardiac data. She and Dr. Joshua Hare (Co-Founder and Chief Science Officer) clarified that for ELPIS II, the FDA supports a composite primary endpoint combining RVEF with clinical outcomes. Dr. Hare differentiated Lomecel-B's multifactorial mechanism from VentriGel's structural approach, viewing it as not a strong competitor.

Inquired about the details of the ELPIS I long-term follow-up data, the process for retrospectively collecting more data, the efficacy benchmarks for the pivotal ELPIS II trial's RVEF endpoint, and the competitive landscape for HLHS, specifically mentioning VentriGel.

Answer

The company stated that ELPIS I follow-up was initially for survival only, but they are now working to retrospectively collect more cardiac data, which doesn't require FDA re-engagement. For ELPIS II, the primary endpoint will be a composite of RVEF and clinical outcomes, as agreed with the FDA. Regarding competition, they view VentriGel as having a different mechanism of action and not being a strong competitor to Lomecel-B.

Maanasa Ramesh, on behalf of Boobalan Pachaiyappan from ROTH Capital, asked about the ideal patient profile for deramiocel based on payer research, progress with Japanese regulators, and the composition of the AdCom committee.

Answer

CEO Linda Marbán specified the target patient profile for the label would be the presence of scar tissue (LGE) in the heart or an ejection fraction of 55% or less. She noted that Capricor is actively working with a CRO in Japan with plans for PMDA meetings later this year or early next. Regarding the AdCom, she stated the panelist list is public and the company is preparing with mock panels of experts with similar profiles.

Boobalan Pachaiyappan asked about the price stability of Ohtuvayre for 2025 amid inflation concerns and sought high-level details on the upcoming Phase IIb fixed-dose combination study, particularly regarding the FEV1 efficacy markers.

Answer

CEO David Zaccardelli confirmed that the company sees the price of Ohtuvayre as stable through 2025. Chief Development Officer Dr. Tara Rheault explained that for the Phase IIb fixed-dose study, the company will measure lung function over the dosing interval. She noted that while pre-dose trough FEV1 will be measured, it is not expected to be the primary endpoint, similar to the approach taken with Ohtuvayre, due to the operational difficulty of measuring it for a twice-daily drug.

Boobalan Pachaiyappan of ROTH Capital Partners asked about the price stability of Ohtuvayre for 2025 and sought details on the planned Phase IIb fixed-dose combination study, particularly the FEV1 efficacy marker.

Answer

CEO David Zaccardelli confirmed that the price for Ohtuvayre is expected to remain stable through 2025. Dr. Tara Rheault, Chief Development Officer, explained that for the fixed-dose combination study, the primary endpoint is unlikely to be pre-dose trough FEV1 due to the operational challenges of measuring it for a twice-daily drug. Instead, the study will focus on lung function over the full 12-hour dosing interval.

Boobalan Pachaiyappan asked about the real-world refill process, including any required testing, and inquired about the real-world side-effect profile, specifically regarding psychiatric events listed on the FDA label.

Answer

Chief Commercial Officer Chris Martin described the refill process as highly organized, with specialty pharmacy partners proactively contacting patients to ensure adherence. Executive David Zaccardelli addressed safety, stating that the company's active pharmacovigilance program has not identified any side effects inconsistent with the product's label. He confirmed the real-world side-effect profile is consistent with what was observed in clinical trials.

Boobalan Pachaiyappan asked about potential headwinds from the newly approved Dupixent, especially in the triple-therapy patient segment. He also inquired about a separate Phase II study on sputum markers and how its results would be integrated into the company's broader strategy.

Answer

Executive David Zaccardelli stated they do not see Dupixent as a headwind, as it targets a narrow patient sub-population and highlights the overall unmet need for new therapies. He and Chief Development Officer Dr. Tara Rheault explained the sputum study is a small, mechanistic trial designed to further characterize Ohtuvayre's anti-inflammatory pharmacology, building on previous data and the strong ENHANCE trial results.

Boobalan Pachaiyappan of H.C. Wainwright & Co. asked for insights into the termination of past partnerships with Takeda and Sarepta, and how those lessons apply to future deals. He also inquired about the current employee headcount.

Answer

CEO Carsten Brunn explained that Takeda's termination was due to their strategic exit from AAV gene therapy, while Sarepta made an internal decision not to proceed. He expressed confidence in monetizing current assets. Brunn also clarified that no new reduction in force (RIF) was being announced, as significant headcount is required for the Sobi-reimbursed work on SEL-212.

Boobalan Pachaiyappan of H.C. Wainwright asked how the recent FDA approval of Filspari might impact Selecta's IgA Nephropathy (IgAN) program, inquired about key biomarkers and the target patient population for IgAN, and sought clarification on whether the Astellas collaboration requires the agent to reach skeletal and cardiac muscles.

Answer

Chief Medical Officer Peter Traber positioned their IgAN program as a novel, complementary approach that targets the underlying IgA immune complexes, unlike other therapies. He identified urinary protein and eGFR as key biomarkers and noted patient segmentation is under consideration. Regarding the Astellas deal, Dr. Traber clarified that Xork works systemically on neutralizing antibodies, so its effect is independent of the gene therapy's tissue target.

Boobalan Pachaiyappan of H.C. Wainwright asked about the impact of a recent competitor approval on the IgAN program, key biomarkers for IgAN, the target patient population, and whether the Xork-gene therapy combination needs to reach skeletal and cardiac muscle.

Answer

Chief Medical Officer Peter Traber described Selecta's IgAN approach as novel and complementary, as it directly targets IgA immune complexes. He identified urinary protein and eGFR as key biomarkers and noted patient segmentation is still under evaluation. Traber also clarified that Xork works systemically by cleaving circulating antibodies, making it effective regardless of the gene therapy's target tissue, as long as it's delivered systemically.

Boobalan Pachaiyappan from H.C. Wainwright asked for details on the MMA Phase I study design, including the number of patients to be enrolled and the expected timeline for initial data.

Answer

President and CEO Carsten Brunn explained that while the primary endpoint is at one year, there will be an initial 3-month readout for each patient assessing safety, disease biomarkers, and neutralizing antibodies. A safety monitoring board will review data from each patient sequentially. He did not provide a specific data release date but noted data would be shared throughout the next year.

Boobalan Pachaiyappan inquired about the release timeline for top-line data from the Janssen epilepsy trial, the clinical advancement schedule for the Indivior collaboration candidate, updates on initiatives to unlock value from dipraglurant, and the company's current cash runway guidance.

Answer

CEO Tim Dyer explained that the Janssen trial data release is contingent on whether a third cohort is initiated, with more definitive guidance expected by year-end 2023. For the Indivior collaboration, a candidate is expected to be selected for IND-enabling studies in 2024. On dipraglurant, the company has pivoted to post-stroke recovery, with preclinical profiling underway alongside partnership discussions. Dyer also confirmed a cash runway extending into 2024, supported by a significantly reduced cash burn and non-dilutive funding for major programs.

Boobalan Pachaiyappan from H.C. Wainwright asked about the competitive threat of new potassium competitive acid blockers to Talicia, the strategic balance between achieving early profitability and pursuing faster growth, details on a potential GI drug acquisition, and the commercial outlook for COVID-19 therapeutics.

Answer

COO Gilead Raday and SVP of Marketing Rob Jackson highlighted Talicia's superior efficacy against resistant H. pylori as a key competitive advantage. CEO Dror Ben-Asher affirmed the priority is achieving cash flow breakeven in H2 2022 while maintaining growth, but declined to comment on acquisition talks. Gilead Raday also noted the long-term potential of their antiviral programs for pandemic preparedness.

Boobalan Pachaiyappan from H.C. Wainwright inquired about European market research for opaganib, the potential design of the RHB-107 Phase 3 study, partnership plans for the trial, expectations for the upcoming cholangiocarcinoma data, and the R&D cost outlook for 2022.

Answer

COO Gilead Raday stated that market research is global and ongoing, with CEO Dror Ben-Asher noting rising COVID-19 cases in Europe. For RHB-107, Gilead Raday confirmed they are analyzing Part A data before discussing the next steps for a large Phase 3 study with the FDA. Dror Ben-Asher added that they are in partnership discussions and expect the trial to be funded by external sources. Regarding cholangiocarcinoma, Gilead Raday mentioned a promising signal of activity has been observed, with full data expected in Q2. CFO Micha Ben Chorin projected relatively low R&D investment for 2022 as part of a broader cost reduction program.

Boobalan Pachaiyappan from H.C. Wainwright asked about preliminary feedback from Key Opinion Leaders (KOLs) on using FIO2 as a clinical parameter for opaganib. He also inquired about the expected data from the RHB-107 Phase 2/3 readout and the competitive landscape for serine protease inhibitors in COVID-19 treatment.

Answer

CEO Dror Ben-Asher confirmed that the company has interacted with KOLs and received feedback that using FIO2 is a feasible parameter. He clarified that the upcoming RHB-107 topline readout is for Part A of the study and will primarily focus on safety, though efficacy signals may be observed. He also noted that while there are other protease inhibitors in development, they target different classes than RHB-107.

Boobalan Pachaiyappan inquired about the status of the rifamycin data analysis with Cosmo, expectations for the opaganib I-SPY COVID trial, potential future studies of opaganib in Delta variant patients, and the status and plans for RHB-104 in Crohn's disease.

Answer

CEO Dror Ben-Asher confirmed the rifamycin data is still under evaluation with their partner. Regarding opaganib, he stated that next steps for the main Phase 2/3 study depend entirely on the upcoming data, while the I-SPY trial is a parallel effort subject to FDA clearance. He also noted that opaganib's label is unlikely to be variant-specific and that a confirmatory Phase 3 study for RHB-104 is planned, focusing on mucosal healing as an endpoint.