Silvan Tuerkcan

Silvan Türkcan inquired if the company has observed patients switching from checkpoint inhibitors to Iptrozy following the NCCN guideline changes. He also asked for the high-level strategic thinking behind the pivotal trial plans for sacrocitinib in both high-grade and low-grade glioma.

Answer

CEO Dr. David Hung explained that while specific patient data is hard to track, the NCCN guidelines now contraindicate immunotherapy in ROS1-positive lung cancer, making a ROS1 inhibitor the clear clinical choice. For sacrocitinib, he highlighted its potential advantages over the competitor in both low-grade (higher ORR) and high-grade (durable CRs) glioma, noting that ongoing FDA discussions are focused on establishing registrational pathways for both indications.

Silvan Türkcan inquired if the company has observed patients switching from checkpoint inhibitors to frontline Iptrozy following the NCCN guideline changes. He also asked for the company's high-level strategy for sacrocitinib's pivotal plans in high-grade and low-grade glioma.

Answer

David Hung, Founder, President & CEO, responded that while specific switching data is hard to track, there is broad recognition that a ROS1 agent is the appropriate therapy, with IO now being contraindicated. Regarding sacrocitinib, he emphasized the goal of designing registrational trials for both high- and low-grade glioma, highlighting the drug's superior response rates in early data, and noted that trial designs will be finalized after concluding FDA discussions.

Silvan Türkcan of Citizens JMP asked for commentary on the pricing dynamics for cabozantinib, particularly concerning the impact of 340B volume on reimbursement.

Answer

CFO Christopher Senner confirmed that the 340B segment volume increased by four percentage points, now representing over 24% of total volume. This shift to a highly discounted segment is impacting gross-to-net, which he now projects will be closer to 30% for the year.

Silvan Tuerkcan asked about Exelixis's business development appetite in the current market environment and whether any roadblocks exist for potential transactions.

Answer

President and CEO Michael Morrissey affirmed that the company is 'open for business' and actively seeking high-conviction assets in GU and GI oncology. He stressed the focus is on assets that can improve the standard of care, not on 'cheap' but risky deals. He indicated the key factors remain finding the right asset at the right time and valuation, with no specific roadblocks mentioned.

Silvan Tuerkcan asked for an update on Exelixis's early-stage synthetic lethality pipeline assets, including expected data timelines and the company's view on the competitive landscape.

Answer

Chief Scientific Officer Dana Aftab and Chief Medical Officer Amy Peterson responded. Aftab highlighted that XL-309 and XL-495 are substantially differentiated from competitors due to advantages in pharmacokinetics (PK) and selectivity. Peterson added that the development team is intensely focused on advancing these best-in-class assets, which have the potential to expand beyond current treatment paradigms.

Silvan Tuerkcan of Citizens JMP sought confirmation that the FDA specifically agreed to a primary endpoint that is objective and not effort-based.

Answer

CEO Sean Nolan explicitly confirmed, 'It's not effort-based. It is objective, and it's very clinically meaningful.' He reiterated that the endpoint is based on gains of function or restoration of lost function, which is meaningful to patients, clinicians, and payers, and that data collected in Part A will be predictive for the pivotal Part B trial.

Silvan Tuerkcan inquired about the dose equivalency between Taysha's TSHA-102 and Neurogene's therapy, considering the different administration routes and Taysha's recent biodistribution data.

Answer

CEO Sean Nolan referenced recent ESGCT data from 29 non-human primates, which showed that Taysha's intrathecal delivery achieves widespread biodistribution comparable to direct-to-brain administration. He and President Sukumar Nagendran attributed the lower effective dose to the higher transduction efficiency of their self-complementary vector design, noting both delivery routes have now shown proof of concept.

Silvan Tuerkcan asked for more details on the previously reported SAE related to the immunosuppressive regimen and inquired when the safety committee might eliminate the 42-day dosing stagger.

Answer

CEO Sean Nolan confirmed the SAE was resolved and deemed not treatment-related, allowing the program to advance. Regarding the dosing stagger, he explained that any change would require a discussion with the IDMC after sufficient safety data is collected, suggesting it's a future possibility. President and Head of R&D, Sukumar Nagendran, added that for intrathecal delivery, regulators have shown flexibility on staggers when the benefit-risk profile is appropriate.

Silvan Tuerkcan asked for an update on the MGD024 Phase 1 study, which has been ongoing for about 1.5 years, inquiring about a potential timeline for data and whether a Gilead opt-in decision point is approaching this year.

Answer

Dr. Stephen Eck, SVP, Clinical Development and Chief Medical Officer, explained that the MGD024 dose escalation has been slow due to a cautious trial design required by the FDA, starting at very low doses. He confirmed they are getting near, but have not yet reached, the maximum tolerated dose. Dr. Eck expressed hope that a Gilead decision point could occur this year.

Silvan Tuerkcan of Citizens JMP asked about the MGD024 program, inquiring if any of Gilead's opt-in decision points could occur in the next year, potentially leading to an announcement.

Answer

Dr. Scott Koenig, President and CEO, explained that the MGD024 dose escalation study is proceeding well but requires a slow escalation per FDA guidance. He stated he could not determine when the study will complete or when Gilead might make an opt-in decision, as Gilead has the right to wait until all Phase I data is available.

Asked about the timeline for the adjudication of patient deaths, whether the DSMB is reviewing them, and for an explanation of the high number of unconfirmed responses, particularly in the high-dose arm.

Answer

The executive expects the death adjudications will be completed by the time of the H2 2024 conference presentation and confirmed the DSMB is reviewing the data. He explained that the high number of unconfirmed responses is a result of the time lag required for confirmatory scans (every 8 weeks), with many patients still on study awaiting their next scan.

Silvan Tuerkcan of Citizens JMP asked about the timeline for the adjudication of patient deaths and inquired about the high number of unconfirmed responses, particularly in the high-dose arm of the TAMARACK study.

Answer

Dr. Scott Koenig, President and CEO, stated he presumed the adjudication of deaths would be complete by the time of a medical conference presentation in H2 2024, and confirmed the DSMB is reviewing the data. He explained that the unconfirmed responses are a matter of timing, as a second scan, performed every 8 weeks, is required for confirmation.

Silvan Tuerkcan asked if near-term readouts from the Allogene collaboration would trigger milestone payments and requested a breakdown of R&D spending, particularly the portion reimbursed by AstraZeneca.

Answer

CBO Arthur Stril clarified that the company's cash runway guidance to mid-2027 is conservative and has heavily discounted potential milestone payments from partners. He also explained that research activities for the AstraZeneca collaboration are fully reimbursed, which significantly offset Cellectis's net cash burn in 2024.

Silvan Tuerkcan asked about the upcoming presentation of quality of life data in HAE, seeking to understand what might be shown and how it could clarify the market opportunity.

Answer

CMO David Lebwohl did not disclose specific results but indicated that a therapy that is easy to administer and subsequently frees patients from disease events would be 'very favorable' from a quality of life perspective. He encouraged listeners to watch for the presentation.

Silvan Tuerkcan asked about the MAGNITUDE-2 trial, specifically when it would be initiated in the U.S. and what the eventual split of U.S. versus ex-U.S. patients would be.

Answer

CEO John Leonard clarified that the study will be conducted entirely outside the United States. This approach allows for a placebo-controlled trial design, which was developed in agreement with the U.S. FDA, who will accept the ex-U.S. data for a potential BLA filing.