Aleniglipron

1月12日，全球生物制药公司硕迪生物（前身为ShouTi Inc.）向美国证券交易委员会递交了IPO上市的S-1文件，计划募资1亿美元，此金额仅供参考，实际募资金额以最终结果为准。 硕迪生物是一家临床阶段的全球生物制药公司，专注于开发和提供创新口服疗法，以应对各类慢性疾病。凭借其独特的基于结构的药物发现和计算化学技术平台，该公司能够研发出针对代谢、心血管及肺系统等疾病的口服小分子疗法。由首席执行官Raymond Stevens博士与全球领先的药物发现公司Schrödinger共同创立，硕迪生物已成功吸引到包括BVF Partners、Deep Track Capital、Eight Roads Ventures、F-Prime Capital、启明创投和红杉资本中国在内的全球顶尖投资者财团的支持，累计筹集资金达1.98亿美元。公司的初期焦点集中在G蛋白偶联受体（GPCR）上，这是一种在多种生理和病理过程中发挥关键作用的靶点。目前，市场上每三种上市药物中就有一种与GPCR相关。借助世界顶尖的GPCR技术，硕迪生物致力于设计出能够克服生物制剂和肽疗法局限性的差异化小分子疗法。 ▲ 重点产品GSBR-1290 硕迪生物目前正处于研发阶段，其重点产品GSBR-1290是一款口服小分子GLP-1R激动剂，旨在治疗2型糖尿病和肥胖症。该产品已于2022年9月顺利完成1期单次递增剂量研究，显示出良好的耐受性，并具备剂量依赖性的药代动力学和药理学活性。硕迪生物已向FDA提交了一份IND申请，以支持启动T2DM和肥胖症的1b期概念验证研究，并于同年9月获得FDA批准。进入2023年1月，公司启动了1b期多次递增剂量（MAD）研究，并计划进一步向FDA提交方案修正案，以过渡到T2DM和肥胖症的2a期概念验证研究，预计将于2023年下半年启动。 ▲ 其他研发项目与合作 除GSBR-1290外，公司还致力于开发下一代GLP-1R候选药物，这些药物均具备独特特性，旨在带来额外益处。最近，ANPA-073这款口服小分子APJR激动剂也备受瞩目，其1期SAD和MAD研究于2022年9月圆满完成，为特发性肺纤维化（IPF）和肺动脉高压（PAH）患者带来了新的治疗希望。APJR靶点不仅吸引了硕迪生物的关注，还吸引了安进、BMS、CohBar、Apie Therapeutics、FibroGen、Galapagos、Galecto、Pliant Therapeutics、Gilead、Roche和Boehringer Ingelheim等众多行业领军企业的竞相研发。 同时，公司也在探索一种分化的溶血磷脂酸1受体（LPA1R）抑制剂，以期为IPF患者提供更多治疗选择。 ▲ GPCR药物研发的挑战 G蛋白偶联受体（GPCR）作为人类基因组中最大的膜蛋白家族，在人类健康中发挥着至关重要的作用。迄今为止，已有约475种上市药物针对100多个独特的GPCR进行治疗，然而，仍有220多种GPCR等待临床探索，这无疑为药物研发领域带来了广阔的发展空间。 ▲ 硕迪生物的技术突破 许多GPCR特性使其成为重要的药物靶点，这些特性包括与多种信号分子的相互作用、参与众多生理和病理过程，以及其细胞表面表达，使得细胞外药物能够与其结合。为了应对这些挑战，硕迪生物已开发出一个独特的平台，该平台基于创始人25年的技术积累，旨在发现能够有效靶向GPCR的小分子药物。硕迪生物的平台在药物研发过程中实现了GPCR结构与结合位点的可视化，加速了药物研发进程。 Raymond Stevens博士在药物开发领域贡献卓越，特别是推动了基于结构的药物研发。他深度参与了多个治疗分子的研发历程，这些分子后来衍生出多种突破性药物，如BioMarin公司开发的Palnziq®。此外，Raymond Stevens博士创立的Receptos公司推出的Zeposia®是一种针对S1PR1受体的GPCR激动剂，于2020年获批多发性硬化症治疗，2021年又获批准用于溃疡性结肠炎的治疗。 硕迪生物在2019年4月成功筹集到3200万美元的A轮融资，每股定价为1.6667美元。2020年3月，该生物技术公司又迎来了新的融资里程碑，成功筹集到2600万美元的A+轮融资，每股定价为2.0313美元。此次融资活动得到了斯道资本、F-Prime、红杉中国和启明创投等知名投资机构的鼎力支持。2021年7月，硕迪生物再次迎来融资佳绩，成功筹集到1亿美元的B轮融资，每股定价为4.0483美元，吸引了众多新投资机构的积极参与。2022年4月，硕迪生物再次取得融资突破，成功筹集到3300万美元的超额认购资金。 2022年2月，硕迪生物宣布成立全资子公司——倍勘生物（Basecamp Bio），旨在进一步拓展其研发领域并寻求与药物研发合作伙伴的携手共进。倍勘生物的成立，为C-suite成员提供了更多发展机会，并且股权架构显示现有投资者的持股比例。

Created with CanvaAI † Viking Therapeutics CEO Brian Lian is watching the growth of interest in MASH and obesity but prepared to go it alone. For the seven companies chasing Metsera before Pfizer finally won with a $4.9 billion offer, there’s a little company called Viking Therapeutics they may want to know about. And according to analysts, they probably already do. Viking is steaming ahead with its clinical program, according to a third quarter earnings update on Wednesday afternoon. The company’s Phase III VANQUISH trials are enrolling quickly and on track to complete and there’s $715 million in the bank to fund it all. The update showed that the little metabolic disease company is “running on all cylinders,” according to Truist Securities. On Thursday morning, Viking’s shares spiked 7% to $33.75, a recovery for the biotech that, along with its peers in the battered industry, has fallen nearly 22% year to date. The company has also suffered some staggering blows due to a readout for key obesity med VK2735 that failed to live up to analyst expectations. Analysts on Thursday were pleased with Viking’s progress but still wanted to know what the company thought about Pfizer and Metsera . One analyst, after congratulating management on the quarter, asked CEO Brian Lian to comment on what he felt were the “favorable/unfavorable” aspects of the deal for Metsera. Lian wouldn’t bite. “Oh gosh. We typically don’t comment on other people’s deals. I think it’s a much better question for Pfizer or Metsera management team. I don’t really have any additional color than what’s out there in the public domain,” he said during the Wednesday earnings call. But that didn’t stop analysts from speculating on whether Viking will be next as they summarized the earnings presentation. Truist noted that Metsera faced seven suitors in the quest for an M&A deal. “This points to continued pharma interest in GLP1 space and we think there’s strategic value to VKTX,” the firm wrote, adding that Viking is probably undervalued. Lian did, however, speak to the potential interest in Viking’s MASH program, VK2809, which the company has been looking to partner. Lian said the space has seen a resurgence lately with deals from Roche , GSK and Novartis . “Obviously, the space has come back a little bit into focus for investors and partners. And yes, I think we have seen a little bit of that uptick in interest,” he said, adding that the MASH drug and obesity assets make Viking an attractive company. “We have two fantastically valuable assets in the same company. So I think we’re in a really, really good position, and we have seen a little bit of interest in that—in the MASH asset.” Even with the increased interest in MASH and metabolic diseases, Lian said Viking’s strategy on partnering and its commercial future has not changed. “We’re certainly receptive to outside interest and nothing’s changed with respect to our thoughts that having a larger party involved would be very helpful in driving the program through commercialization. That said, I don’t think it’s mandatory,” he continued. “We’re prepared to go alone, but we’re also prepared to engage with anybody who is interested.” Enthusiasm Rising William Blair noted that Viking has plenty of cash to fund operations for about two years. This would include a readout for the Phase I maintenance trial of oral and subcutaneous VK2735. It could even extend to the Phase III VANQUISH-1 and VANQUISH-2 trials of subcutaneous VK2735 in obesity and obesity with diabetes, respectively, the firm added. VK2735 is a dual GLP-1/GIP agonist that Viking is developing as an oral pill and subcutaneous formulation. The oral version previously showed 12% body weight reduction at 13 weeks in a Phase II trial that read out in August, which analysts at the time heralded as “strong efficacy.” But the results showed a difficult safety profile, with 20% of the participants dropping out of the trial due to side effects. The adverse events were predominantly gastrointestinal in nature, including mild to moderate nausea and vomiting. The results sent Viking’s shares tumbling 40% . Nevertheless, Viking has seen rapid enrollment in its later-stage trials for VK2735, William Blair pointed out. “We believe that the rapid enrollment rate reflects a high degree of patient and physician enthusiasm for the VK2735 program,” the analysts wrote. Enrollment in VANQUISH-1, which features patients who are non-diabetic with obesity, is expected to wrap up by the end of the fourth quarter. Enrollment for VANQUISH-2, which includes patients who are diabetic, is expected to run until the end of the first quarter. Total enrollment across the two programs will hit 5,600 participants. Viking will also introduce an auto-injector in the program for the subcutaneous doses. While it’s still early days for the VANQUISH program, Lian said there so far have not been any issues with patients adhering to the treatment plan. “The VANQUISH studies have enrolled maybe a little ahead of schedule. I think that reflects a fair amount of enthusiasm for the program, and we’re happy to see that [there’s] nothing notable at this point,” he said on the call. “We’re still pretty early in the treatment windows. There’s nothing that’s suggestive of any persistence issues or anything like that. It’s so far going very well according to plan.” Viking’s Phase I maintenance trial “could give VK2735 commercial edge,” according to Truist. The study will start patients on subcutaneous VK2735 and then transition to the pill version. Truist expects this transition to be relatively seamless, with limited risk of a resurgence of gastrointestinal side effects, since the patients will be receiving the exact same molecule, just in a different form. Data from that trial are expected in the second half of 2026. But analysts questioned Viking management regarding how they will go about pitching an obesity maintenance drug to the FDA, given there hasn’t been a regulatory precedent set for that yet. Lian admitted to the challenge at the FDA and said payers will be key in commercial discussions, which are still in the early stage for that potential indication. “We think these data could be quite powerful in providing evidence for how to keep people on therapy. That’s the best way to realize the long-term benefits, and that’s the way payers will ultimately save money is keeping people on and increasing persistence rates,” Lian said. “And that’s exactly why we’re exploring these different maintenance options.” Truist will be keeping an eye on Viking’s competitors, including Structure, which is expecting Phase II data for the oral GLP-1 aleniglipron in the fourth quarter. The company is exploring slower titration with higher doses, so the focus will be on the safety data. Yesterday, Terns announced the discontinuation of oral GLP-1 drug TERN-601 after a readout showed underwhelming weight loss results and a questionable safety profile. Asked about the dynamics in the obesity market, Lian said Viking has adjusted dosing and titration to ease side effects that have previously cropped up with VK2735. The company is doing a lot of work to find the right doses across all different treatment options they are exploring for the therapy. “It’s really, really difficult to develop these therapeutics. The attrition is, I guess, just a reflection of those challenges,” Lian said. “But I think we feel really good about where we are in the competitive landscape with the oral peptide.” Elsewhere, Viking plans to kick off a Phase I study for the amylin and calcitonin dual-agonist program in the first quarter of 2026, which is slightly delayed from the previously planned initiation in the fourth quarter of this year.