Ted Tenthoff

Ted Tenthoff inquired about the specific data to be expected from ARV-102 at the ADPD conference and the criteria or 'bar' for advancing ARV-102 into registrational studies for Progressive Supranuclear Palsy (PSP).

Answer

Randy Teel (President and CEO) clarified that a PSP update ahead of registrational trial initiation is unlikely due to timing. Noah Berkowitz (CMO) stated that the ADPD data will focus on ARV-102's safety and biomarker patterns (LRRK2 degradation, GPNMB, CD68) in Parkinson's patients, comparing them to previously observed healthy volunteer data.

Ted Tenthoff inquired about the specific data to be presented for ARV-102 at the ADPD conference and the criteria or 'bar' for initiating registrational studies in Progressive Supranuclear Palsy (PSP).

Answer

President and CEO Randy Teel clarified that the ADPD data, from Parkinson's patients, would be relevant for both PD and PSP, preceding any PSP registrational trial. Chief Medical Officer Noah Berkowitz indicated the ADPD presentation would focus on safety, LRRK2 degradation levels, and biomarker patterns in Parkinson's patients.

Ted Tenthoff inquired about the allocation of restructuring costs between R&D and G&A, and asked for more detail on the expected ARV-102 data release later in the year, specifically for the single ascending dose cohorts in Parkinson's patients.

Answer

CFO Andrew Saik clarified that restructuring costs were split between R&D and G&A, with most stock-based compensation in R&D. CMO Noah Berkowitz added that for ARV-102, the company expects to present the full healthy volunteer dataset and initial single ascending dose (SAD) data from Parkinson's patients at an upcoming conference, which should signal the program is on track compared to healthy volunteer results.

Ted Tenthoff sought further clarification on Alnylam's external partnering strategy, asking if the focus would be on complementary technologies such as delivery types or other RNA mechanisms.

Answer

Yvonne Greenstreet, CEO, confirmed that the company is indeed looking for areas with good strategic fit and complementary opportunities, with delivery types being one potential approach. She emphasized a judicious approach to external innovation that accelerates internal efforts and complements the current portfolio. Tolga Tanguler, Chief Commercial Officer, reiterated the focus on technologies that help bring medicines to more patients more rapidly.

Ted Tenthoff of Piper Sandler Companies inquired about Karyopharm's biggest concerns for the upcoming myelofibrosis (MF) data readout and how the company is preparing for three major data readouts in 2026 across myelofibrosis, endometrial cancer, and multiple myeloma.

Answer

CEO Richard Paulson stated the company is excited for the opportunity and well-prepared, highlighting the significant prescriber overlap between multiple myeloma, myelofibrosis, and endometrial cancer which allows for leveraging existing commercial capabilities. Chief Medical Officer Reshma Rangwala added that she is not worried but rather encouraged by the comprehensive data for selinexor in MF, which has shown compelling improvements in SVR35, TSS, and disease modification markers, suggesting the potential to meaningfully improve upon the standard of care.

Ted Tenthoff of Piper Sandler & Co. asked for an update on the remaining work for the NDA submission and whether the company anticipates an FDA Advisory Committee (ODAC) meeting for iopofosine.

Answer

COO Jarrod Longcor explained that most NDA modules are complete, with the primary remaining task being the integration of the final CLOVER-WaM clinical study report. Regarding a potential ODAC meeting, Longcor said he wouldn't be surprised by a request, while SVP, Medical, Dr. Andrei Shustov, called it a 'tossup' but confirmed the company is preparing for the possibility.

Inquired about the expansion of the Immuno-STAT platform beyond the current clinical assets, specifically asking about other antigens like KRAS and whether potential partners are interested in existing products or using their own proprietary antigens with the platform.

Answer

The company is expanding its pipeline to target primary cancer drivers like mutated KRAS (G12V, G12D), MAGE-A4, and PRAME. There is interest from potential partners in both the company's existing pipeline and in deploying the platform for their own bespoke antigens. The Neo-STAT platform is highlighted as a flexible solution for this, enabling a 'plug-and-play' approach for various antigens and personalized immunotherapy.

Ted Tenthoff of Piper Jaffray sought clarification on the specific issues causing the IND hold for the AML trial and the expected timeline for resolution.

Answer

SVP of Clinical Development, Dr. Mythili Koneru, explained the hold relates to FDA requests for quality and technical data on two third-party reagents used in manufacturing, which are not present in the final product. She confirmed a complete response was submitted on October 28, 2019, with a 30-day FDA review period. President and CEO Peter Hoang added that such requests are not atypical in the cell therapy space.