IBI363 (PD-1/IL-2) demonstrated encouraging signals in IO-failed and cold tumors, especially in IO-resistant sq-NSCLC. IBI363 is a potential FIC PD-1/IL-2bsAb with a differentiated α-biased IL-2 arm, distinct from other IL-2 mAbs that eliminate the receptor α. IBI363 has shown broad-spectrum anti-tumor effects for IO-failed and cold tumors, including IO-resistant NSCLC, melanoma, and 3L+ CRC.
Especially, for later-line IO-treated sq-NSCLC patients (n=37, 76% with ≥2 prior treatment) receiving IBI363 at ≥0.3mg/kg, the ORR reached 35.1% and the mPFS reached 5.5 months, which were much better than the current SoC docetaxel's 12.7% ORR and 3.9 months of mPFS (link). We expect the 3mg/kg Q3W dose to deliver even better efficacy results with a preliminary 100% ORR observed in the 3mg/kg Q3W dose cohort (n=6) in sqNSCLC patients. In addition, for 3L+ CRC, the 15% ORR of IBI363 mono (1mg/kg Q2W) was better than that of fruquintinib (4.7% ORR in FRESCO trial). We think IBI363 has potential to combo with VEGF or chemo for treatment of CRC. Safety was overall tolerable. In the 3mg/kg Q3W cohort (n=38), rate of Gr≥3 TRAEs was only 13.2% and there was no TRAE leading to treatment discontinuation. Two out of the 347 patients died due to TRAEs. Innovent has started a US Ph2 study (NCT06281678) of IBI363 and is considering the initiation of MRCT pivotal trials in NSCLC and melanoma.
CLDN18.2 ADC showed good potential in PDAC. IBI343 (CLDN18.2 ADC)demonstrated encouraging signals in the highly underserved PDAC, with 40.0% ORR observed in the 10 CLDN18.2 positive (≥60%) PDAC patients receiving IBI343 at 6mg/kg. Only 25.7% Gr≥3 TRAEs were observed, and the percentage of Gr≥3 AEs of neutropenia, nausea and vomiting were lower than its peers. For GC, we expect the Company to release PoC results of IBI343 in 3L+ GC at ESMO GI in Jun.
Innovent plans to start an MRCT Ph3 trial of IBI343 in GC (NCT06238843).
Additionally, IBI389 (CLDN18.2/CD3) also demonstrated encouraging preliminary PoC results in GC and PDAC, while the safety profile requires further clinical follow- up given the 58.3% rate of Gr≥3 TRAEs in the Ph1 study (n=120), in our view.
Mazdutide (GLP-1/GCGR) released competitive Ph3 results in obesity. In thePh3 GLORY-1 trial (link), mazdutide demonstrated strong weight loss results, - 14.84% (6mg) vs -12.05% (4mg) vs -0.47% (placebo) at week 48. Mazdutide also brought significant decreases in LDL-C, serum uric acid and ALT. Mazdutide (6mg) had 80.2% reduction in liver fat content (LFC) for subjects with baseline LFC ≥10%, indicating its potential in liver steatosis improvement. Mazdutide's weight loss results were better than semaglutide and comparable to tirzepatide, in our view. Recall that tirzepatide achieved -19.9% (15mg) vs -14.4% (10mg) vs -2.4% (placebo) weight loss in the China SURMOUNT-CN trial at week 52, and semaglutide had -12.8% (2.4mg) vs -3.0% (placebo) weight loss in the STEP 7 Asia trial at week 44.
Additionally, mazdutide demonstrated better safety profile with AE leading discontinuation rate of 0.5% (6mg) vs 1.5% (4mg), compared to 7.0% of tirzepatide (15mg) and 2.8% of semaglutide. The results support mazdutide's NDA in China, with approval expected in 1H25. As a front-runner in dual-targeted GLP-1 drugs for obesity, we expect mazdutide to gain considerable market share in China.
Maintain BUY. We see the FIC potential of Innovent's innovative PD-1/IL-2 assets and look forward to the potential overseas out-licensing deals in the future. We revise our DCF-based TP from HK$55.00 to HK$55.75 (WACC: 10.0%, terminal growth rate: 4.0%)