Morphic Therapeutic, Inc.

1 整体表现 LLY从Tirzepatide上市以来，一直持续着标准的“戴维斯双击”态势，本季度算是首次大幅miss预期，导致绩后当晚一度大跌15%，市值回到$800b左右，然而一旦增长放缓预期坐实，那过去两年疯狂提升的估值中枢（现价相当于全年业绩指引的60x市盈率左右），可能就要给双杀提供巨大空间了…… 收入同比增长42%（除去23Q3出售奥氮平的一次性收入影响），跟前几个季度的同比增速其实相当，然而问题是出在环比，毕竟全市场的共识预期就是T药正在从胜利走向胜利。 从不同市场的对比来看，滞涨的问题就出在美国市场，欧洲的环比增长还是在线的，而且电话会里的说法就是Tirzepatide在美国市场的提价过程已经中止（上个季度还依然存在），具体销量的问题后文详述。 本季度终于迎来了首次对全年预期的调减，不过其实并不像看起来那么夸张，收入只是微调了指引上限，EPS调减是由于三季度对Morphic的收购，这反过来表现了公司对Tirzepatide增长信心的维持（至于信心靠不靠得住另当别论）。 2 Tirzepatide 首先就有一个场外因素的微妙迹象，这是ST双雄对决以来首次两家公司没有在邻近时间发布季报，导致我们还需要蹲守一周才能看到双方的攻守之势，是巧合还是有意为之，就纯评臆测了。 在整体销售额爬坡节奏上，T药在上个季度大幅爆发之后，本季度Mounjaro和Zepbound环比双双走平，单季度销售额合计停止在$4.4b；在我们尚不清楚S药表现的情况下，好像这就是S药两个季度之前的剧情重现，如果一周之后坐实二者都可能增势放缓，那就可能需要对GLP1星辰大海做重新评估了。 鉴于这种微妙的局面，个人觉得有必要开始提防地辩证甄别这两家公司对待GLP-1市场的表述了，毕竟似乎矛盾的信息在逐渐增多。以下提出几个仅就T药而言不太好解释的问题（S药的情况等下周再说）： 1）Q3停止增长的原因 公司延续上个季度的说法（参见【医苑观畴】2024年二季度海外药企进展更新：礼来LLY），Q2在渠道里有铺货、而Q3则存货下降了，所以导致真实销售额分别受到一正一反的影响。 那么我们把铺货的合理性放一边（在后面供需关系再论），按公司说法Q2存货增加的影响约是美国市场销售额的20%、Q3存货减少的影响则是5%，那么这样调整下来依然不改变Q3环比增速大幅放慢的事实，特别是Zepbound上市才没多久环比就降到30%多。 再结合IQVIA的处方量数据（穷人买不起只能从别人那儿盗图了），基本上符合环比增速放缓的结论。 2）供需关系 从上个季度开始，ST两药突然从供不应求秒变供需平衡，这剧情实在让人摸不着头脑，特别是T药在仍然坚持“今年产能同比扩张为去年的1.5倍”的说法下，产能就这样华丽地不再紧缺了，还特意强调上半年客服问题里有20%都是供应链、而现在基本上没有这种问题了，须知即便在增长停滞的情况下今年销售的同比增长可远不止50%，也就是有一部分需求凭空被解决了。 再就是回到前面提到的铺货，无论如何我是难以理解在需求有倍增空间而产能只放大50%的情况下，开始出现渠道库存挤压、乃至于存货高达销售额20%，这用单剂量小规格获批、冷链等理由都很难解释。 3）未来预期 公司给出了Q4同比增长50%的指引，也与全年业绩指引的中位数相吻合，即Q4需要完成约$14b的销售额。 我们简单假设T药以外其他品种Q4同比增长5%（前三个季度同比增速都不到这个数），轧差的结果就是T药Q4需要达到$6.7b才能完成全年目标，这就意味着环比增长50%以上。 然而，公司有清楚说明了认为未来季度环比增长大约在25%，那50%和25%到底哪个可信一点呢？ 3 其他已上市产品 T2 肿瘤板块其实表现非常也非常抢眼（不过几乎完全没人care、电话会分析师一个问的都没有），CDK4/6抑制剂Abemaciclib在去年获批了辅助治疗等早期乳腺癌适应症后持续保持增势、LTM累计已逼近$5b，市场份额还在不断逼近50%；RET抑制剂Selpercatinib也在不声不响中单季度爬坡到$114m，BTK C481S抑制剂Pirtobrutinib爬坡倒还有些乏力。 自免板块就更无人问津，虽然IL-17A单抗Ixekizumab相当给力、LTM累计已超过$3b，不过剩下确实难成气候，JAK抑制剂Baricitinib看起来也就是$1b的水平了（隔壁Upadacitinib今年铁定要破$5b），新晋的Lebrikizumab和Mirikizumab这爬坡就跟没爬差不多。 其他唯一的看点CGRP单抗Galcanezumab，好像也有点止步不前，连带着对整个偏头痛市场的空间都要打问号。 4 在研管线 Donanemab在终于获批之后，又宣布了三期临床TRRAILBLAZER-ALZ6研究的积极结果，在改进给药方案后（第1个月350mg、第2个月700mg、第3个月1,050mg、随后1,400mg），能有效将ARIA-E风险从24%降到14%，且在减少淀粉样板块和P-tau217等终点与标准质量方案相当。 IL13单抗Lebrikizumab在搞定CRL之后终于获得FDA批准，用于治疗中重度特应性皮炎，该药在ADvocate1/2两个三期临床中展现出优秀的效果，此外还在近期公布的ADapt三期临床中证明对Dupilumab经治患者依然有较好的效果。 Tirzepatide在SURMOUNT-1之后的持续研究中，验证了持续治疗三年可降低T2D风险94%、体重平均降低22.9%。 另两个被高度关注的GLP-1资产，口服Orforglipron和三靶Retatrutide在今年都不会有新消息出炉，前者的几个临床似乎又往后推迟了几个月，公司自己对这个管线的信心好像一步步被坐实；在电话会上，公司表达了Orfo应定位为Sema等注射剂型的补充，可影响20-25%的患者群体，也不寄希望于大规模患者从注射向口服转化。 除此以外，值得关注的进展还包括：SERD药物Imlunestrant公布三期临床积极结果，KRAS G12C抑制剂Olomorasib启动1L NSCLC三期临床，长效胰岛素公布QWINT-1/3/5等三期临床等效结果；此外，用于治疗类风湿性关节炎的PD-1激动剂Peresolimab被终止开发。 如今的医药行业，几乎是全球看LLY/NVO、这两家看S/T的局面，而Tirzepatide在三季度陡然出现增长停滞可谓一石激起千层浪，似乎背后确实出现了很多对GLP-1空间的隐忧，究竟需求拐点是否已现，我们应通过一周后Semaglutide的业绩情况、以及此后一段时间保持高度关注。 最后，再嘚瑟一把知行合一，从上个季度就觉得GLP-1这味儿好像有那么点不大对，LLY这估值水平又太依赖持续兑现高增长，遇到风吹草动出现双杀的动能很足，于是咬着牙下了几次空单，算是等到了赚笔零花钱的机会~

Eli Lillys seemingly inexorable growth hit a speed bump Wednesday, when the Indianapolis drugmaker reported earnings for the third quarter that missed Wall Street expectations and sent shares down sharply.Overall, revenue reached $11.4 billion between July and September, up 20% from the same period last year but higher by only 1% versus the second quarter and well below the consensus forecast of about $12.1 billion.Lillys sales and stock price have swelled on surging demand for the companys GLP-1 medicines Mounjaro and Zepbound, which it respectively sells for diabetes and obesity.The company has had difficulty meeting that demand, though, leading to shortages that have hampered the drugs availability. (In October, the Food and Drug Administration officially removed Mounjaro and Zepbound from its shortage list, but is now reconsidering that decision.)Compared to the third quarter last year, sales of the two drugs are significantly higher, respectively reaching $3.1 billion and $1.26 billion during the period. But both totals were lower than analysts expected and roughly flat compared to the second quarter.Lilly said wholesalers purchasing fewer doses negatively impacted U.S. sales of Mounjaro and Zepbound by mid-single digits as a percent of total sales in the country. Wholesalers had previously stocked up toward the end of the second quarter, according to Lilly.Shares were down by double digits early Wednesday, dragging down a market capitalization that had ballooned beyond $900 billion previously. The stocks of other obesity drugmakers were affected, too, with rival Novo Nordisk falling by more than 3%.Lilly also trimmed its guidance for the year, shaving $600 million off the top end of its estimated revenue range, which it now puts between $45.4 billion and $46 billion.Lucas Montarce, the companys new CFO, said the guidance update was done to reflect Lillys balancing of demand creation activities and new market launches with its production. This is the driver for lowering the top end of the range, he said on an earnings call Wednesday.The company also cut its earnings per share guidance to between $12.05 and $12.55 on a reported basis to reflect both the lowered revenue forecast and accounting charges taken in association with Lillys acquisition of Morphic Therapeuticearlier this year.David Risinger, an analyst at Leerink Partners, described Lillys GLP-1 drug sales as a big miss versus expectations but, writing in a client note Wednesday, said his team views the investment thesis as unchanged since the company is just getting started in commercializing obesity products globally.Company executives said something similar, noting how, after accounting for the wholesaler impacts, underlying demand continues to grow.We do see acceleration of both brands in [the third quarter]over [the second quarter]in actual consumption, said company CEO David Ricks, who noted he expects that to continue as Lilly begins advertising for Zepbound.Along with Novo, Lilly has led the pharmaceutical industrys charge into obesity treatment. Zepbound, which contains the same active ingredient as Mounjaro, can help clinical trial participants lose as much as one-fifth of their body weight. Further testing has shown it holds benefits for people with heart failure and sleep apnea, too.A more recent study found that weekly injections also reduced the risk of developing diabetes, and Lilly is testing the drugs effects on heart and kidney disease as well.Novos drugs Ozempic and Wegovy have proved similarly potent in curbing weight, diabetes and heart risk.In response to that success, pharma and biotechnology companies are racing to develop their own competitors, testing new twists on targeting GLP-1 or attempting to replicate the drugs effects in a pill, rather than injection.Both Lilly and Novo have successors of their own, though. Two of Lillys, retatrutide and orforglipron, are now in Phase 3 testing, with data expected next year and in 2026. Novo, meanwhile, is awaiting a major readout for its combination drug cagrisema later this year.Editors note: This story has been updated with executive commentary. '

The weather is getting cooler, but biotech’s recovery is heating up. After a years-long wait-and-see game exhausted many industry insiders, recent signals indicate a mostly promising direction for drug developers. The third quarter, which ended Monday, was up and down, with the Yen carry trade fiasco and the typical August lull. But then came a long-awaited interest rate cut, and a mini IPO revival began. Two more rate cuts are expected by the end of the year, and more are anticipated in 2025. Nine months into the year, biotech is on track to surpass the total amount of private financing from 2023, according to a new quarterly analysis from investment bank William Blair. There have been at least 10 crossover rounds each quarter for three consecutive quarters, the first stretch of its kind since the heydays of 2021. And the proportion of extension rounds dropped in the third quarter, which “potentially” means “we have passed the peak of the financing overhang in the private markets,” according to the William Blair bankers. There were five IPOs in the third quarter, and three more are now in line, including Septerna, a Phase 1 biotech that filed Wednesday . The number of follow-on offerings and private investments in public equity slowed last quarter, but they picked up after Labor Day. The first nine months of 2024 already surpassed 2023’s totals by 34%. Biopharmas have done 189 secondary offerings, raising $33.9 billion in total proceeds year-to-date, according to William Blair. Last year’s count was 186 offerings and $25.3 billion raised. Private megarounds held steady throughout the year, as well, with 23 such financings in the first quarter, 27 in the second and 23 in the third, according to an Endpoints News tally. “Combined with improving sentiment, lower rates, and better financing window (record levels of follow-ons) — Q3’s event scoreboard was supportive for XBI and biotech funds,” Jefferies analyst Michael Yee wrote in an Oct. 1 note. For the firms funding new drugs and the next generation of startups, the money was flowing, too. In recent weeks, multiple venture capital funds announced some of the biggest biotech VC hauls ever. Bain Capital Life Sciences raised $3 billion, as did ARCH Venture Partners . Flagship Pioneering kicked off the third quarter with its own $3.6 billion pool of capital. Others included TPG ‘s $580 million, venBio’s $528 million, DCVC Bio’s $400 million and Asabys’ $200 million. One sore spot was European pharma stocks , with dips in share price at Roche (down about 6.5%), Novo Nordisk (down about 1.5%) and AstraZeneca (down about 1.5%). “Obesity remains an important theme for the sector considering the outsized moves in large caps,” the Jefferies analysts wrote Tuesday evening, citing updates from Roche’s GLP-1 pill and GLP-1/GIP injectable , and Novo’s Phase 2a CB1 program . “We think excitement and enthusiasm remain high, but performance could be more data-driven with more winners and losers as the landscape continues to evolve and mature over the coming months.” Another pain point was M&A and partnerships, which William Blair bankers characterized as “anemic” in the third quarter. Eli Lilly’s $3.2 billion purchase of Morphic Therapeutic in July was the only public company buyout of more than $1 billion during that period. There were a few other deals that could eclipse $1 billion in total value, but those are contingent on the acquirees — Jnana , Nerio and Dermavant — reaching certain milestones. Also driving M&A activity were first-generation AI biotechs and multiple commercial-stage drugmakers, including Valinor Pharma, Ironshore Therapeutics , G1 Therapeutics , Revance and Dermavant. Most of the deals have not yet closed. “We expect some pause into the election,” Yee wrote Tuesday, “but lower rates and [continued] financing (funds putting money to work) support a higher XBI as we seek to hopefully break the key $100 level.” The XBI closed on Monday, Sept. 30, at $98.80, though it had crossed the $100.00 threshold in mid-July and a few times since.