Kalpit Patel

Kalpit Patel asked for confirmation if the dose levels for the asthma trial are the same as BROADEN2, how Kymera is enriching for FeNO in the target patient population, if the 12-week FEV1 data could align with the 16-week BROADEN Phase II study, and about competitive trial enrollment dynamics in AD versus asthma.

Answer

Nello Mainolfi, Founder, President, and CEO, confirmed that dose levels are the same across AD and asthma. He stated that the asthma study includes high eosinophils (>300) and high FeNO (>25) for patient selection. He reiterated that AD data is expected by mid-next year, and asthma data by the end of next year. Regarding competitive dynamics, he noted strong enthusiasm for Kymera's studies in both AD and asthma, driven by innovative science, well-established biology, the oral drug format, and compelling early data, which is translating into good enrollment so far.

Kalpit Patel asked to confirm if KT-621 dose levels are consistent across the BROADEN2 (AD) and BREADTH (asthma) trials, how Kymera is enriching for FeNO in the asthma patient population, if the 12-week FEV1 data from BREADTH could align with the 16-week BROADEN2 data, and about competitive trial enrollment dynamics in AD versus asthma.

Answer

CEO Nello Mainolfi confirmed that KT-621 dose levels are consistent across the AD and asthma trials. He explained that the asthma study enriches for FeNO by selecting patients with high eosinophils (>300) and high FeNO (>25). He clarified that AD data is anticipated by mid-next year, with asthma data expected by late next year. He also noted strong enthusiasm and good enrollment for Kymera's studies in both AD and asthma, driven by innovative science, established biology, oral convenience, and compelling early data.

Kalpit Patel from B. Riley Securities inquired about preclinical comparisons of KT-621 to dupilumab in atopic dermatitis models, specifically regarding ear thickness, and asked about the projected human equivalent dose based on mouse model data.

Answer

CEO Nello Mainolfi clarified that Kymera focuses on Th2 biomarkers and asthma models over ear thickness, which is a less specific measure. He advised that dose projections should be based on dog and monkey data, not mouse data, due to protein binding differences, suggesting the human dose range will be broadly similar to the IRAK4 program.

Kalpit Patel asked about the degradation kinetics for the STAT6 program, referencing a previous protein rebound observed with the IRAK4 program, and questioned what steps are being taken to ensure accurate measurement of target knockdown.

Answer

President and CEO Nello Mainolfi clarified that the IRAK4 issue was specific to using flow cytometry in a multi-site patient study, where sample handling can introduce variability, unlike the more robust mass spectrometry used in healthy volunteer trials. He assured that for the KT-621 studies, they have planned for multiple opportunities and methods to ensure accurate protein level measurements.

Kalpit Patel asked why the growth in active patients is not keeping pace with new patient start forms, inquiring if it's due to insurance delays, discontinuation rates, or a mix, and how this gap might evolve. He also asked if the discontinuation rate is expected to fluctuate meaningfully between now and year-end.

Answer

Anish Bhatnagar, Chairman and CEO, attributed the lag primarily to the time required for benefits assessment (around 30 days) after a start form is received. Meredith Manning, Chief Commercial Officer, added that it's a mix of factors but expressed satisfaction with the conversion of start forms to active patients. Anish Bhatnagar also stated that while the discontinuation rate might fluctuate, he doesn't foresee major changes from the 15-20% range, which is considered acceptable for the condition.

Kalpit Patel asked about the reasons for the observed gap between quarter-over-quarter growth in active patients and new patient start forms, considering factors like insurance-related delays and discontinuation rates, and how this gap might evolve.

Answer

Anish Bhatnagar, Chairman and CEO, attributed the gap primarily to the time required for benefits assessment (approximately 30 days), creating a natural lag between start forms and active patients. Meredith Manning, Chief Commercial Officer, added that it's a mix of factors but expressed satisfaction with the conversion of start forms to active, reimbursed patients.

Kalpit Patel asked about Revolution Medicines' disclosure strategy for the pivotal update in second-line pancreatic cancer (RASolute 302) if the interim progression-free survival (PFS) analysis is missed, but the overall survival (OS) driven readout has not yet crossed the pre-specified boundary.

Answer

Chairman and CEO Mark A. Goldsmith stated that the company could not provide a definitive answer at this time and would decide on appropriate disclosure based on the data. He reiterated that the study is OS event-driven and powered for OS, making it more powered for PFS. He acknowledged that a split result, where PFS has crossed but OS has not yet reached statistical significance, is conceivable, and the company would assess the situation at that point.

Kalpit Patel asked about Revolution Medicines' disclosure strategy for the pivotal update in second-line pancreatic cancer (RASolute 302) if the interim PFS analysis is missed but the OS readout has not yet reached statistical significance.

Answer

Mark Goldsmith, Chairman and CEO, stated that Revolution Medicines could not provide a definitive answer at this time and would decide on appropriate disclosure once the data are available. He reiterated that the study is OS event-driven and powered for OS, making it more powered for PFS, and acknowledged that a split result (PFS crossed, OS not yet significant) is a conceivable scenario.

Kalpit Patel asked about Ascendis Pharma's internal assessment of the competitive landscape for chronic hypoparathyroidism, specifically regarding emerging agents like encaleret, and whether the longer-term outlook for YORVIPATH accounts for their potential impact.

Answer

Jan Møller Mikkelsen, President and Chief Executive Officer, strongly dismissed encaleret as a meaningful treatment for PTH deficiency, calling it an 'idiotic idea.' He emphasized that encaleret, a calcium-sensing receptor modulator, does not provide hormone replacement therapy like YORVIPATH, which addresses multiple organ systems (brain, bone, kidney). He stated that encaleret is only relevant for a small subset of ADH1 patients with a specific mutation, not for general PTH deficiency, and therefore, it is not factored into YORVIPATH's outlook.

Kalpit Patel asked about Ascendis Pharma's internal perspective on the competitive landscape for chronic hypoparathyroidism, specifically regarding emerging agents like Encaleret, and whether the longer-term outlook for YORVIPATH incorporates the potential impact from such agents.

Answer

Jan Møller Mikkelsen, President and Chief Executive Officer, strongly dismissed Encaleret as an 'idiotic idea' for PTH deficiency, arguing it is not a hormone replacement therapy and only addresses calcium absorption, failing to provide the multi-organ benefits of PTH. He stated that while it might make sense for ADH1 patients, it is not a meaningful treatment for general PTH deficiency and has not been factored into YORVIPATH's outlook.

Kalpit Patel asked if a benefit in overall survival would be needed for full approval of STELLAR-303 or STELLAR-304, given recent FDA guidance, and if STELLAR-304 needs to look better than CABO plus Nivo on a cross-trial basis.

Answer

P.J. Haley (EVP of Commercial) emphasized that the non-clear cell RCC population in STELLAR-304 is distinct from the broader RCC market, including CABO plus Nivo studies, and cross-trial comparisons should be avoided. He reiterated that STELLAR-304 is the only Phase III trial specifically studying this underserved population, and positive results would be highly impactful.

Kalpit Patel asked about the anticipated need for overall survival benefit for full approval of STELLAR-303 or STELLAR-304, given recent FDA guidance, and whether STELLAR-304 (with sunitinib control) needs to demonstrate superiority to cabozantinib plus nivolumab on a cross-trial basis.

Answer

P.J. Haley (EVP of Commercial, Exelixis) emphasized that non-clear cell RCC is a distinct patient population from broader RCC studies, including cabozantinib plus nivolumab. He stated that STELLAR-304, as the only Phase III trial studying this underserved population, would be impactful with positive results, and cross-trial comparisons should be made carefully due to different patient populations.

Inquired about Emrosi's inventory levels in the distribution channel, early real-world feedback from prescribers, the source of new patients (new vs. switches from Oracea), and the concentration of prescribers.

Answer

The company estimates typical launch inventory of 2-4 weeks in the channel. Early feedback from the 660 unique prescribers is 'tremendously positive,' driven by strong clinical data and real-world results. The initial launch strategy focuses on new patients, with an expectation that doctors will begin switching existing Oracea patients as they gain comfort and see results. The early onset of efficacy is a key driver for adoption.

Kalpit Patel inquired about the potential impact of Oracea's recent generic entry on DFD-29's launch, key performance indicators for investors to track post-launch, and the anticipated SG&A expense ramp for fiscal year 2025.

Answer

Claude Maraoui, Co-Founder, President and CEO, stated that the Oracea generic is not considered a critical factor for payer negotiations. He advised investors to monitor total prescriptions, unique prescriber adoption, and market share in the initial quarters. Regarding 2025, he indicated that SG&A would increase to support the launch but noted it was too early to provide specific guidance.

Kalpit Patel from B. Riley Securities asked about any preliminary discussions with payers regarding the DFD-29 drug profile and sought confirmation on the company's guidance to achieve cash flow breakeven in fiscal year 2024.

Answer

Co-Founder, President and CEO Claude Maraoui stated that recent market research with payers covering over 200 million lives showed an overwhelmingly positive reception for DFD-29, indicating favorable coverage negotiations post-approval. Chief Financial Officer Joseph Benesch reaffirmed that the guidance for achieving full-year positive non-GAAP adjusted EBITDA remains unchanged, noting the core business is already contribution positive when excluding launch costs.

Andy, asking on behalf of Kalpit Patel from B. Riley, inquired about the 2023 revenue outlook, specifically whether growth from the four key promoted brands could offset declines from legacy assets prior to the DFD-29 launch. He also requested more detail on the factors driving the sequential decline in the overall Accutane market.

Answer

CEO Claude Maraoui stated that the primary impact from Targadox generic competition was absorbed in 2022 and that other legacy brands are expected to remain stable. He affirmed the company's expectation for growth from its four key launched brands in 2023. Regarding Accutane, he attributed the recent market softness to a 12% sequential decline in the broader isotretinoin market, while highlighting that Journey Medical successfully maintained its market share of over 11%.

Kalpit Patel from B. Riley Securities asked for specific inventory levels at the end of Q1 versus Q4, whether new patient starts are outpacing discontinuations, and for an explanation of the Q1 cash burn relative to the net loss.

Answer

CFO Michelle Robertson reported that inventory was at the high end of the range at ~3.5 weeks at Q4-end and the low end at ~2.5 weeks at Q1-end. She attributed the higher Q1 cash burn to typical annual bonus payouts and inventory investments. CCO James Ziegler added that while early patients had shorter treatment durations, a promising 25% of new starts are now in earlier lines, which should improve persistence.

Kalpit Patel from B. Riley Securities asked for the specific timing of when the revenue flattening began. He also inquired if physicians were targeting specific patient subgroups, such as those with high transfusion burdens, and whether the company still stood by its projection of over $1 billion in peak revenue potential.

Answer

Jim Ziegler, CCO, pinpointed the start of the flattening trend to around the Thanksgiving holiday, based on rolling averages. He noted a lack of precise data on subgroup targeting beyond the approved indication. He strongly reaffirmed the company's belief in the blockbuster potential of Rytelo, stating 'Rytelo works' and that the key is to educate a broader physician audience to drive trial and adoption over time.

Kalpit Patel of B. Riley Securities questioned the rationale for choosing a complex royalty and debt structure over a simpler equity raise, and asked for any early data on patient adherence and continuation rates.

Answer

EVP & CFO Michelle Robertson explained the hybrid financing structure was chosen for flexibility and to reduce dependency on equity markets, thereby avoiding shareholder dilution. EVP & CCO Jim Ziegler stated it is too early for definitive data on continuation rates but noted that anecdotally, they appear consistent with clinical trial results.

Kalpit Patel inquired about the strategic differences between the TarGeT-D glioma study and the planned company-sponsored Phase 2 trial, and also asked about any other existing ANDA filers for TAVALISSE.

Answer

President and CEO Raul Rodriguez and Chief Medical Officer Lisa Rojkjaer clarified the glioma trial strategies. Dr. Rojkjaer explained that the TarGeT-D study evaluates olutasidenib as a maintenance therapy combination in newly diagnosed adolescent and young adult patients, while the upcoming company-sponsored trial will focus on recurrent glioma. Mr. Rodriguez confirmed that the company is not aware of any other ANDA filers for TAVALISSE.

Kalpit Patel asked about the R289 program in lower-risk MDS, inquiring if Grade 3/4 adverse events were dose-dependent, how much more data would be presented at ASH, and what differentiates R289 from other IRAK inhibitors.

Answer

Chief Medical Officer Lisa Rojkjaer stated that details on dose-dependency of adverse events would be shared at the ASH meeting in December. She confirmed the ASH data would include an additional three months of follow-up. President and CEO Raul Rodriguez highlighted that R289's key differentiator is its dual inhibition of both IRAK1 and IRAK4, which is expected to provide more profound inhibition of inflammatory cytokines compared to IRAK4-only inhibitors.

Kalpit Patel from B. Riley Securities asked for a breakdown of Q1 Revuforj revenue between new patient starts and refills, and for an early estimate of the median duration of therapy.

Answer

Chief Commercial Officer Steven Closter responded that it is too early to provide a specific breakdown, as the data is still maturing, but confirmed that both new starts and refills are building strongly, with some patients on their fifth refill. He stated that a definitive median duration of therapy will take a couple more quarters to establish, but early compliance data is encouraging.

Kalpit Patel of B. Riley Securities asked if there's a minimum efficacy threshold for KMT2A patients to be included on the frontline label and what additional analyses for the pivotal KMT2A cohort might be presented at ASH.

Answer

Dr. Neil Gallagher, President and Head of R&D, explained the frontline trial is powered for NPM1, and while they will look for consistency in KMT2A patients, the study is not designed to test a statistical hypothesis for that group. He also indicated that more detailed analyses of the KMT2A data would be presented at ASH but did not specify the details.

CalPIT Patel inquired about preclinical comparisons of the STAT6 program to Dupilumab, specifically regarding the atopic dermatitis ear thickness model, and asked about the human equivalent dose for a specific preclinical dose in mice.

Answer

Founder, President, and CEO Nellie Monofi explained that dose projections are more accurately based on dog and monkey models, which suggest a lower single-digit mg/kg dose, rather than the higher dose used in mice. She also clarified that the company focuses on TH2 biomarkers in asthma models rather than the composite ear thickness outcome.

CalPIT Patel from B. Riley asked for the rationale behind testing additional doses in the expanded IREC4 trials and inquired if these new doses would be outside the previously tested 50-200mg range.

Answer

CEO Nello Manalfi explained that adding more doses is a standard regulatory expectation for dose-ranging to establish an efficacy-safety relationship before a Phase 3 trial. This expansion is intended to accelerate the overall timeline to a registrational study. He could not comment on specific doses but confirmed they would be within the previously disclosed range.

Asked about the number of different DEEs being targeted in the upcoming study, the expected analysis in the open-label extension data presentation, and the status of the partial clinical hold on LP659.

Answer

The company clarified the Phase III study is a broad DEE study that includes LGS, with more details to be shared in September. The upcoming OLE data is from the 6-month cutoff. The partial clinical hold on LP659 is still in place but is expected to be resolved soon with the submission of the MAD study proposal.

Kalpit Patel from B. Riley asked what the company considers a clinically meaningful delta in efficacy for the ongoing study and sought clarification on the scope of the intellectual property for FB-401, specifically if it covers the bacterial species itself.

Answer

CEO Paul Wagner explained that based on feedback from thought leaders, a 10 to 15-point difference in the EASI score versus placebo would be clinically significant, given a clean safety profile, which is paramount in pediatrics. Regarding IP, he detailed that the company's 11 issued patents are broad, covering the foundational NIH technique for culturing the bacteria, the composition of matter, methods of use for treating diseases like atopic dermatitis, and kits, providing a very solid IP position.