Merdad Parsey
Chief Medical Officer at Gilead Sciences
Thank you, Johanna. The clinical highlight of our third quarter was the release of our promising, Phase 2 data for Trodelvy in combination with pembrolizumab in first-line metastatic non-small cell lung cancer, highlighting Trodelvy's potential to bring a much needed treatment alternative for patients. More broadly, we continued to progress our increasingly diverse pipeline of 60 ongoing clinical programs, spanning Virology, Oncology, and Inflammation.
Starting with our Virology programs on slide 17, we have 10 clinical programs with our long acting capsid inhibitor, lenacapavir, including two Phase 3 studies underway in PrEP. I'm pleased to share that we have completed enrollment earlier than anticipated for our Phase 3 PURPOSE-1 trial evaluating lenacapavir for prevention in adolescent girls and young women. Our Phase 3 PURPOSE-2 trial in cis-men and trans-women and men, and non-binary people continues to enroll well, and we could have an opportunity to share data from one or both PURPOSE trials in late 2024, ahead of schedule. We are targeting our first approval for lenacapavir in prevention in late 2025, potentially making lenacapavir the first six monthly dosing regimen available for PrEP.
Turning to treatment, we continue to make strong progress on evaluating nine candidate partners for lenacapavir. Of the remaining candidates, six are already in Phase 1 or 2. We expect to share updates on at least four of these in 2024, including data from our Phase 1 trial of GS-1720, our once-weekly long-acting oral integrase inhibitor to be combined with lenacapavir, and from our Phase 2 ARTISTRY-1 trial evaluating a once-daily, oral combination of lenacapavir and bictegravir for virologically suppressed, treatment-experienced people living with HIV. We plan to share results from both trials at a conference in early 2024, and we look forward to advancing these programs into the next phase of development. We're also pleased to share that enrollment for our Phase 2 program evaluating our lenacapavir plus bNAbs combination dosed every six months is progressing very well and is another program we expect to update you on next year. Putting this all together, our data continue to support our confidence that lenacapavir has the potential to transform HIV treatment and prevention globally.
Turning to Oncology on slide 18, to date, Trodelvy has been delivered to more than 20,000 patients across three approved indications since our launch three years ago. Trodelvy remains the first and only marketed TROP2-directed antibody drug conjugate to achieve meaningful overall survival benefit in two of its indications. With that said, we are seeing both growing real world evidence and clinical trial data supporting not only the approach we are taking for Trodelvy's clinical development across tumor types, but also Trodelvy's unique ADC construct. In particular, Trodelvy is the only ADC to have a high seven-to-eight drug-to-antibody ratio that is able to deliver a highly potent SN-38 payload directly into the tumor microenvironment through its hydrolyzable linker. As a result, in our studies to date, Trodelvy has shown a potentially differentiated safety profile with regards to ILD and stomatitis. We look forward to sharing more emerging Trodelvy data in 2024 as we continue to expand Trodelvy across tumor types and lines of therapy. Our comprehensive clinical development program for Trodelvy consists of more than 30 active or planned clinical trials across eight tumor types.
In 2023, we've shared several datasets demonstrating clear signals of activity for Trodelvy across several indications. For example in the ASCO meeting this past June, we presented data for Trodelvy that demonstrated encouraging preliminary ORR and PFS in relapsed or refractory endometrial cancer patients in the Phase 2 TROPiCS-03 basket trial. More recently at the ESMO meeting, we presented additional, early data from TROPiCS-03 showing promising ORR in both relapsed or refractory head and neck squamous cell carcinoma and previously treated extensive stage small cell lung cancer.
We reported strong data from EVOKE-02 at World Lung in September, shown on slide 19, establishing clear proof-of-concept for Trodelvy plus pembro in first-line, metastatic non-small cell lung cancer. In the PD-L1 high cohort, Trodelvy plus pembro demonstrated ORR of 69% including unconfirmed responses. This compares favorably to the historical pembro monotherapy benchmark with response rates of 45% and 39% in KEYNOTE-024 and KEYNOTE-042, respectively. As a reminder, we are currently enrolling patients with 1L PD-L1 high metastatic non-small cell lung cancer in our registrational Phase 3 EVOKE-03 study. Preliminary data from the PD-L1 TPS less than 50% cohort has also been encouraging, demonstrating an ORR of 44%, similar to previous trials that evaluated pembro plus chemotherapy. These results inform our plans to expand into broader first-line non-small cell lung cancer patient populations across all PD-L1 expression levels. We are looking forward to sharing further analysis from EVOKE-02 that will highlight the efficacy of Trodelvy and pembro across both squamous and non-squamous histologies in first-line, metastatic non-small cell lung cancer patients.
Moving to our TIGIT program on slide 20, an initial update of one arm of the Phase 2 EDGE-Gastric study was presented in an ASCO plenary session earlier today. The study found that the addition of dom and zim to a FOLFOX chemo regimen showed encouraging 77% six month PFS and 59% ORR, including unconfirmed responses, in first-line metastatic upper GI cancer. In patients with PD-L1 high tumors, the ORR was an impressive 80% and the six month PFS was 93%. We're pleased to see that dom and zim added to the standard-of-care was generally well tolerated, with an adverse event profile similar to antiPD-1 plus FOLFOX. These results increase our confidence in the ongoing registrational Phase 3 STAR-221 trial in the similar first-line gastric, gastroesophageal junction, and esophageal adenocarcinoma population and our broader anti-TIGIT program. Although anti-TIGIT will not work in every tumor type, we are excited to see dom has shown encouraging efficacy and tolerability in the tumor types we have advanced to Phase 3 studies, including 1L non-small cell lung cancer and upper GI cancer.
Turning to Cell Therapy on slide 21, we are continuing to work to expand the benefits of cell therapy to even more patients, with eight ongoing trials in earlier lines, new indications, or new settings. We also have an extensive early-stage pipeline, where we are exploring allogeneic CAR Ts, including healthy donor and iPSC-derived cell therapies, as well as natural killer and invariant natural killer T cell therapies. Beyond therapies, we continue to invest in manufacturing innovation to maintain our position as the world's leading cell therapy manufacturer and drive more rapid treatment for patients.
We will continue to explore emerging disease areas in cell therapy where we have the potential to apply our expertise to the treatment of difficult diseases. This includes multiple myeloma, where we are pleased that the Phase 2 iMMagine-1 trial of CART-ddBCMA has resumed enrollment, and we share in Arcellx's confidence in the therapeutic profile of CART-ddBCMA to be able to deliver benefit to patients. To that end, the data unveiled in last week's abstract release for the upcoming American Society of Hematology meeting further reinforce CART-ddBCMA's robust efficacy and safety profile where, at 22 months follow-up in the ongoing Phase 1 trial, two-thirds of patients continue to respond, and median survival has not yet been reached. We look forward to additional data and even longer median follow-up next month. In the meantime, we are further strengthening the body of clinical evidence highlighting the long-term durability and survival benefits of both Yescarta and Tecartus at the ASH meeting in December.
Finally, and before I hand over to Andy, the team's progress on key 2023 clinical milestones is shown on slide 22. As is expected with a diverse and large clinical portfolio, not all our programs will benefit patients the way we hope they will, and the ENHANCE and ENHANCE-2 programs evaluating magrolimab have both been discontinued based on futility analyses. The ENHANCE-3 study remains under partial clinical hold in front line unfit AML, and we continue to evaluate the progress of this and other Phase 2 solid tumor trials for magrolimab.
With regards to some of the remaining milestones for 2023, as referenced previously, we look forward to sharing data from ARTISTRY-1 at a medical conference in 2024. For our HIV prevention studies, we continue to expect to have our first patient in for the PURPOSE-3 and PURPOSE-4 clinical trials by the end of this year. Additionally, we remain on-track to initiate our Phase 2 PALEKONA trial, evaluating our potentially first-in-class TPL2 inhibitor for ulcerative colitis later this year. Our TPL2 inhibitor represents one of our many oral agents for inflammation.
Looking beyond 2023, we will share our target 2024 milestones in due course, but it is already clear that it will be a rich year of data updates for Gilead, including potential updates or regulatory filings for obeldesivir, lenacapavir, Trodelvy, and CART-ddBCMA.
With that, I'll hand the call over to Andy. Andy?
