INNOVENT BIOLOGICS(1801.HK):PROMISING POC RESULTS OF THE POTENTIAL FIC ASSET
INNOVENT BIOLOGICS(1801.HK):PROMISING POC RESULTS OF THE POTENTIAL FIC ASSET
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.
IBI363（PD-1 / IL-2）在IO失敗和冷瘤中顯示出鼓舞人心的信號，尤其是在IO耐藥的sq-NSCLC中。 IBI363是一種潛在的FIC PD-1/IL-2bsAb，具有不同於消除受體α的其他IL-2 mAb的分化α偏向的IL-2臂。IBI363顯示了廣譜抗腫瘤作用，包括對IO失敗和冷瘤的影響，包括IO耐藥的NSCLC，黑色素瘤和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.
特別是對於接受IBI363（≥0.3mg/kg）的後線IO治療的sq-NSCLC患者（n = 37，76％有≥2次先前治療），ORR達到了35.1％，mPFS達到了5.5個月，遠高於當前的SoC docetaxel的12.7％的ORR和3.9個月的mPFS（鏈接）。我們預計3mg/kg Q3W劑量將獲得更好的療效結果，在sqNSCLC患者中觀察到3mg/kg Q3W劑量組（n = 6）的初步100％ ORR。此外，對於3L + CRC，IBI363單抗（1mg/kg Q2W）的15％ ORR優於FRESCO試驗中的富昆替尼的ORR（4.7％）。我們認爲IBI363與VEGF或化療聯合治療CRC的潛力巨大。安全性總體可以接受，在3mg/kg Q3W隊列中（n = 38），Gr≥3 TRAE的發生率僅爲13.2％，並且沒有 TRAE導致治療中斷。在347名患者中，有兩人因TRAE死亡。Innovent已開始IBI363的美國Ph2研究（NCT06281678），並考慮在NSCLC和黑色素瘤中啓動MRCT關鍵試驗。
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.
CLDN18.2 ADC在PDAC中表現出良好的潛力。IBI343（CLDN18.2 ADC）在高度未開發的PDAC中展示出令人鼓舞的信號，其中IBI343 6mg/kg給藥的10例CLDN18.2陽性（≥60％）PDAC患者中觀察到ORR達到40.0％。只觀察到25.7％的Gr≥3 TRAEs， 並且粒細胞減少，噁心和嘔吐的Gr≥3 AE的比例低於同類產品。對於胃癌，我們期望公司將在ESMO GI中發佈IBI343在3L + GC的PoC結果。
Innovent plans to start an MRCT Ph3 trial of IBI343 in GC (NCT06238843).
Innovent計劃在胃癌中開始IBI343的MRCT Ph3試驗（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.
此外，IBI389（CLDN18.2 / CD3）在GC和PDAC中也展示了令人鼓舞的初步PoC結果，但考慮到Ph1研究（n = 120）中Gr≥3 TRAEs的58.3％比率，其安全剖面需要進一步的臨床隨訪，我們的看法是如此。
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.
Mazdutide（GLP-1 / GCGR）在肥胖症方面發佈了有競爭力的Ph3結果。在Ph3 GLORY-1試驗（鏈接）中，Mazdutide在48周時顯示出了強勁的減重效果，-14.84％（6mg）vs -12.05％（4mg）vs -0.47％（安慰劑）。 Mazdutide還顯著降低了LDL-C，血清尿酸和穀草轉氨酶。對於基線LFC ≥10％的受試者，Mazdutide（6mg）使肝臟脂肪含量（LFC）減少了80.2％，表明其在改善肝脂肪變性方面具有潛力。根據我們的觀察，Mazdutide的減肥效果優於Semaglutide並可與Tirzepatide媲美。回顧Tirzepatide在中國SURMOUNT-CN試驗中在52周時達到了-19.9％（15mg）vs -14.4％（10mg）vs -2.4％（安慰劑）的減重效果，而Semaglutide在STEP 7亞洲試驗中達到了-12.8％（2.4mg）vs -3.0％（安慰劑）的減重效果。
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.
此外，Mazdutide的安全剖面更佳，AE導致停藥率爲0.5％（6mg）vs 1.5％（4mg），而Tirzepatide（15mg）和Semaglutide的停藥率分別爲7.0％和2.8％。結果支持Mazdutide在中國的NDA，預計在2025年上半年獲得批准。作爲雙靶向GLP-1藥物減肥方面的領跑者，我們期望Mazdutide在中國的市場份額大幅提高。
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%)
維持買入。我們認爲Innovent的創新PD-1 / IL-2資產具有潛在的FIC潛力，並期待未來的潛在境外許可交易。我們將基於DCF的TP從HK $55.00調整爲HK $55.75（WACC：10.0％，期末增長率：4.0％）。
譯文內容由第三人軟體翻譯。