Catherine Novack

Catherine Novack asked about potential reimbursement and pricing for CAH, whether Crinetics anticipates similar pricing power as with PALSONIFY, and if there would be different price points for pediatric and adult patients.

Answer

CEO Scott Struthers stated it's premature to discuss CAH pricing but emphasized the company's work to illustrate the molecule's full value. He noted a strong demand for new CAH agents, given atumelnant's unique pharmacological capabilities, and expressed enthusiasm for the ongoing open-label extension and Phase 3 program.

Catherine Novack inquired about learnings from PALSONIFY's launch regarding reimbursement and pricing power for the upcoming CAH launch, and whether different price points are anticipated for pediatric and adult CAH patients.

Answer

Dr. Scott Struthers, Founder and CEO, stated it is premature to discuss CAH pricing but emphasized the significant unmet need and the unique pharmacology of Atumelnant for CAH patients. He highlighted the enthusiasm from investigators and patient communities for the phase III program, noting the hunger for new agents in CAH.

Catherine Novack of JonesTrading inquired about the potential market for paltusotine in surgically naive acromegaly patients, asking if a significant number of patients forgo surgical resection.

Answer

Chief Commercial Officer Isabel Kalofonos responded that while the company is excited about the data presented at ENDO for pre-surgical patients and believes there is an unmet need, this segment is not being actively considered at this time. She indicated that depending on the final approved label, it might represent a future opportunity.

Catherine Novack asked about paltusotine's commercial prospects, specifically whether Crinetics anticipates payers imposing step-through requirements for treatment-naive patients, potentially based on price.

Answer

Isabel Kalofonos, Chief Commercial Officer, responded that based on their current discussions with payers, they do not anticipate any step-therapy requirements. She conveyed that the feedback has been positive, with payers expected to follow the drug's label for prior authorization.

Catherine Novack inquired about the prioritization of the three non-oncology assets moving toward IND filings this year and which indication management finds most exciting.

Answer

CEO R. Struthers stated that the company's strong balance sheet allows it to advance all programs without needing to prioritize. He noted that the oncology NDC (CRN09682) is furthest along, followed by a close race between the PTH antagonist and TSH antagonist programs, with the ADPKD program also progressing.

Catherine Novack asked what learnings Crinetics took from Neurocrine's pivotal programs in congenital adrenal hyperplasia (CAH) for its own Phase III design and what the standard of care might look like after a potential approval for crinecerfont.

Answer

CEO R. Struthers noted that crinecerfont's potential approval would be a first for CAH. He stated that data from both companies' programs have clarified the roles of different hormones, suggesting that ACTH (Crinetics' target) is the more critical driver of the adrenal axis compared to CRF. He added that Crinetics looks forward to sharing more data and its Phase III plans soon.

Catherine Novack questioned the dose response and relationship between Activin E and fat loss, specifically why WVE-007 showed similar fat loss to competitors with lower Activin E knockdown, and if preclinical modeling data supports better fat loss from 75% to 85% knockdown.

Answer

Paul Bolno, President and CEO, highlighted that Wave's study has larger cohorts and demonstrates highly durable, suppressed Activin E levels over time, which differentiates it. He confirmed that preclinical data showed a clear dose response where Activin E reduction drove further weight loss, primarily fat loss. Bolno expects both time and dose to impact fat reduction, with the 240mg and 400mg cohorts providing opportunities to observe this dynamic range.

Catherine Novack inquired about the dose-response relationship between Activin E and fat loss for WVE-007, noting similar fat loss with potentially lower Activin E knockdown compared to competitors, and asked about preclinical modeling data for 75% to 85% knockdown leading to better fat loss.

Answer

President and CEO Paul B. Bolno highlighted that Wave's study has larger cohorts than some competitors, and they observe highly durable, suppressed Activin E levels over time, which is a key differentiator. He confirmed that preclinical data showed a dose response on Activin E reduction driving weight loss, primarily fat loss. Bolno stated that they expect to see the impact of both time and dose on fat reduction, particularly within the 240mg to 400mg therapeutic range, which aligns with their preclinical models.

Catherine Novack from JonesTrading sought specifics on the WVE-006 multi-dose cohort, asking when dosing was completed, if all patients received all seven doses, and the minimum follow-up for the data release. She also asked about the timing of the WVE-007 cohort two expansion.

Answer

President & CEO Paul Bolno confirmed that for WVE-006, all patients in the 200 mg cohort completed all seven doses and the data remains on track for Q3. Regarding WVE-007, he clarified that the decision to expand cohort two from 8 to 32 participants was made during the quarter based on favorable data, and that dosing for this expanded cohort is now complete, alongside the initiation of the 400 mg cohort three.

Catherine Novack from JonesTrading asked about the required patient numbers for the monthly DMD cohort, whether providers are reassessing gene therapy's risk-benefit profile, and how to interpret Wave's observed increase in serum Z protein in AATD versus a competitor's decrease.

Answer

President and CEO Dr. Paul Bolno stated that the total patient number for the DMD filing will be similar to other exon 53 programs and confirmed that clinicians are reassessing gene therapy risks. Regarding AATD, Dr. Bolno explained that the increase in Z protein is a positive signal, suggesting the breakdown and release of liver aggregates, which aligns with their preclinical models. Chief Scientific Officer Dr. Erik Ingelsson added that focusing on the newly produced M protein is the clearest benchmark for comparing different therapeutic approaches.

Catherine Novack of JonesTrading requested more details on the AATD program's multiple-dose cohorts, including patient numbers and timing. She also asked about the M-AAT protein threshold for success and whether Wave is exploring other siRNA obesity targets beyond INHBE, such as GPR75.

Answer

President and CEO Paul Bolno confirmed each AATD cohort will have 8 patients and reiterated the goal is to restore a stable heterozygous phenotype, with M-protein being the critical measure of editing efficiency, rather than targeting a specific micromolar number. He also noted that Wave is evaluating other metabolic targets, leveraging its potent and durable siRNA chemistry which has shown promise for CNS delivery as well.

Catherine Novack of JonesTrading inquired about the DMD program, asking if there were any unknowns in the accelerated approval pathway for WVE-N531 and how much weight 48-week functional outcomes would carry. She also asked if potential partners for the Huntington's program would want involvement in regulatory discussions.

Answer

CEO Paul Bolno stated that the DMD accelerated approval pathway based on dystrophin as a surrogate is well-established and not expected to change. He noted that consistent dystrophin expression is key for predicting positive outcomes and that 48-week functional data will be important for internal decision-making. Regarding the Huntington's program, he affirmed that partners would have ample opportunity for future regulatory involvement, but the crucial first step was securing initial FDA alignment on a biomarker-driven trial design, which has now been achieved.

Catherine Novack of JonesTrading asked about the timeline from the last patient visit to data analysis for the SELVA trial and which endpoints from the CVM Phase II study are being considered for a potential Phase III trial, considering the FDA's preference for static measures.

Answer

President and CEO Wes Kaupinen stated that data cleaning and analysis can begin immediately after the last patient visit and is expected to take a matter of weeks, keeping the program on track for a Q1 2026 readout. For the CVM trial, he explained that they will analyze all endpoints from the proof-of-concept study before selecting a primary endpoint for Phase III in collaboration with physician experts and the FDA, utilizing both dynamic and static scales.

Catherine Novack asked if the FDA provided any substantive feedback in its Type A meeting acceptance and inquired about the drivers behind the increase in Q2 R&D expenses.

Answer

CEO Linda Marbán confirmed the FDA's response was a standard meeting acceptance with no substantive commentary. CFO AJ Bergmann attributed the higher R&D expense to both late-stage clinical costs for the fully enrolled HOPE-three trial and CMC activities in preparation for a potential commercial launch.

Catherine Novack from Jones Research questioned the company's strategic plan in the event of a Complete Response Letter (CRL) and asked for specific FDA feedback on using LVEF as a surrogate endpoint.

Answer

CEO Linda Marbán explained that if a CRL were issued, the company would unblind its fully enrolled HOPE-3 trial and submit that data to seek approval for the skeletal muscle indication, potentially alongside the cardiac data. She clarified that the FDA views ejection fraction not as a surrogate, but as a direct outcome measure in this rare disease context, a position supported by FDA-funded natural history studies.

Catherine Novack asked for color on Capricor's discussions with the FDA regarding the agency's historical concerns about single-arm studies in DMD, and why the FDA might view the HOPE-2 open-label extension data on cardiac outcomes differently.

Answer

CEO Linda Marbán explained that the FDA's acceptance is based on two key factors. First, the open-label data is compared to a propensity-matched natural history control group from a Vanderbilt consortium. Second, and most importantly, the primary endpoint is cardiac MRI, which is a non-volitional measurement. Unlike functional tests, a patient cannot 'will their heart to be better,' which removes placebo effect bias and gives the agency confidence in the strong, statistically significant treatment effect observed.

On behalf of Catherine Novack, Leona asked for details on the FDA's information request for the Sildenafil Phase III trial, the potential outcomes of the Ovaprene interim assessment, whether all four new products are on a dual FDA/compounding path, and the associated marketing outreach plans.

Answer

CEO Sabrina Johnson clarified that the FDA's request concerned patient-reported outcomes psychometrics, with a response targeted for submission by the end of Q2 2025. For Ovaprene, she stated the July interim review is for safety and study integrity only, with no planned efficacy analysis or sample size adjustments. Johnson confirmed that Sildenafil and DARE-HRT1 are on a dual path (compounding and FDA approval), while the vaginal probiotics are consumer health brands. Near-term marketing efforts will focus on Sildenafil, with DARE-HRT1 outreach increasing next year.

Catherine Novack of JonesTrading inquired about Daré's Ovaprene program, asking about the implications of updated enrollment timing on the top-line data readout and whether an interim data look is planned. She also asked for the commercially compelling Pearl Index target for the contraceptive.

Answer

CEO Sabrina Johnson explained that while half of the target participants are expected to complete six months of use by mid-2025, final top-line timing is not yet set due to varied enrollment rates across study sites. Johnson noted that the company is considering an interim analysis. Regarding the Pearl Index, she stated that the non-hormonal contraceptive market has a wide range of accepted efficacy, and Ovaprene's pre-pivotal data suggests potential effectiveness similar to short-acting hormonal methods, which would be highly compelling for a monthly, hormone-free option.

Questioned the company's cash position and financing strategy, asking about potential inflection points for investors and what strategic partners might need to see. Also sought clarification on the statistical analysis for the first co-primary endpoint and inquired about the future potential of using LUM-201 for patients switching from growth hormone injections.

Answer

The company stated that clarity on the Phase III trial design from the FDA is the key inflection point that gives them confidence in securing financing from investors and advancing discussions with potential ex-U.S. partners. The first co-primary endpoint will be assessed against a pre-defined hurdle of 'clinically meaningful growth' (e.g., 6.7 cm/year), not a direct comparison to a 12-month placebo. Using LUM-201 for patients switching from injections is a future possibility that could be explored in post-market studies, but is not part of the current plan.

Catherine Novack of Jones Research asked for details on the Reproxalap visual acuity data, including the change in the vehicle group and clinical significance, and also questioned the rationale for using RASP modulators in geographic atrophy given the focus on complement in the field.

Answer

President and CEO Dr. Todd Brady clarified that while both the Reproxalap and vehicle groups improved vision, the drug arm's improvement was statistically superior (p<0.0001), which is remarkable in a population with normal acuity. For geographic atrophy, he explained that RASP modulation offers a dual mechanism: a broad anti-inflammatory effect beyond just the complement cascade, and the prevention of RASP-derived metabolites like lipofuscin that form drusen.

Catherine Novack requested clarity on the 2023 timing for INVIGORATE-2 data in allergic conjunctivitis and subsequent filing steps. She also asked about the prioritization of ADX-629 programs and how alcoholic hepatitis data will inform other indications.

Answer

President and CEO Dr. Todd Brady explained that INVIGORATE-2 enrollment will occur during the winter to avoid pollen season, with data expected after enrollment completion in spring/summer 2023. A supplemental NDA could be filed late in 2023. Regarding ADX-629, he noted that positive alcoholic hepatitis data would confirm target engagement, which is crucial for all programs. Indication prioritization is a systematic effort to define the pharmacology of RASP modulation, with future decisions based on trial readouts.

Catherine Novack inquired about the ADX-629 ethanol toxicity study's status and path forward, FDA feedback on the ADX-2191 NDA submission for PVRL, and the commercialization strategy for reproxalap.

Answer

President & CEO Dr. Todd Brady explained that the ADX-629 ethanol toxicity trial is a crossover study looking for signals in hangover symptoms and objective intoxication markers, with potential paths to either an acute or chronic alcoholic hepatitis trial. For ADX-2191, he noted the FDA doesn't require clinical trials for the ocular lymphoma NDA due to existing literature on methotrexate, but wants stability and safety data on Aldeyra's specific formulation. Regarding reproxalap commercialization, Dr. Brady outlined three options: partnering (preferred due to payer contracting leverage), launching internally (feasible in ophthalmology), or a hybrid model, stating the company is financed for any path.

Catherine Novack of Jones Trading asked about the expected R&D spending for the year given the numerous ongoing trials and requested an update on the TRANQUILITY-2 data timeline, specifically asking if the database had been locked.

Answer

CFO Joshua Reed indicated that R&D spending in 2022 is expected to increase compared to 2021 levels due to the high volume of clinical activity. CEO Dr. Todd Brady provided a detailed overview of the post-trial data analysis process, explaining that the TRANQUILITY-2 database was in the final quality control stage and had not yet been locked.