Circle Pharma, Inc.

Welcome back to another edition of Endpoints Weekly! For those that had time off for Presidents’ Week, we hope you had a restful vacation. If you missed any of the headlines, we had a lot of biotech news this week. We covered clinical trial data from an Eylea competitor, Moderna’s flu shot fracas, another rare disease rejection, and an update on a potential psilocybin treatment. And in a potential shift, the pharma industry seems to be signaling that it’s done negotiating with the Trump administration over trying to codify “most favored nation” deals into law, Max Bayer wrote. White House officials have tried to convince lawmakers that industry supports the effort, but it still hasn’t been made clear what exactly Trump’s team is hoping to codify. For an industry so closely tapped into Washington, its failure to pacify the president with concessions is an unexpected turn. Read more from Max here . Have a great weekend, and we’ll see you next week! — Max Gelman 👁️ Ocular Therapeutix is working on a therapy it hopes can compete with the blockbuster drug Eylea in an eye disease called wet age-related macular degeneration, or wet AMD. The biotech read out Phase 3 data this week for its experimental drug Axpaxli, in which 74.1% of patients reached their goal on a test that measures a patient’s vision. Comparatively, this goal was hit by 55.8% of Eylea patients, an observed difference of 18.3 percentage points. The result was statistically significant, with a p-value of p=0.0006. However, this difference underwhelmed Wall Street, sending Ocular’s stock price down more than 20% on the day it released the data. The difference between the treatment and comparator arms might be the issue for shareholders: Judging by remarks CEO Pravin Dugel made at investor conferences last year, Ocular expected this level of performance from Axpaxli, but set expectations for Eylea at about 20%. The control drug did much better than that prediction. Axpaxli should still have a relatively smooth path to FDA approval, senior biopharma journalist Elizabeth Cairns writes . The trial was designed to support a potential superiority label and was agreed to by the FDA. The superiority claim could also mean Axpaxli will leapfrog Eylea HD, the less frequently administered version of Regeneron and Bayer’s drug, and Roche’s newer entrant Vabysmo. The timing for an FDA filing is not yet set, but Ocular is seeking to meet with the agency as soon as possible. Next steps include a second Phase 3 study for the noninferiority of Axpaxli given every six months versus Eylea at 2 mg every two months and Eylea HD every four. And Ocular is eyeing up a much bigger market: diabetic retinopathy. Data from the first of two Phase 3 studies could come next year. 💉 The company announced this week that the two sides have agreed to an amended filing . Following a Type A meeting with regulators, Moderna said it will apply for a standard approval in the 50 to 64 age group and accelerated approval in adults 65 years and older. The company said it will conduct a post-marketing study in the older age group to produce more clinical data. The FDA set an Aug. 5 date to decide on both submissions. If approved, the vaccine could be available for the upcoming flu season. The resolution comes about a week after Moderna announced that it received a refusal-to-file letter, and the ultimate decision followed an unusual path through FDA, Endpoints’ Zachary Brennan reported . Read more here. The FDA rejected yet another rare disease drug from a biotech seeking accelerated approval, this time from Disc Medicine. But this drug was also part of the Commissioner’s National Priority Voucher (CNPV) program, a pilot that aims to significantly shorten the typical 10- to 12-month review times. Disc’s drug was one of the first in the pilot to go through FDA review, and the rejection suggests drugs that are selected won’t be guaranteed an approval. In the rejection letter, FDA officials cited concerns about the surrogate biomarker used in clinical trials. An HHS spokesperson said there “was agreement amongst the review division that a CRL was appropriate and a career official signed off” on the rejection. Analysts viewed the rejection as a surprise, particularly since Disc was one of the first companies to get the voucher. “It’s hard to connect the dots on this one,” Stifel analyst Stephen Willey wrote in a note to investors. Read more here . 🧠 The company announced this week that it met the primary endpoint in a second pivotal trial. The study tested its psilocybin formulation, COMP360, in patients with treatment-resistant depression. But unlike the first pivotal trial, which pitted COMP360 against placebo, this trial compared different doses against each other. The trial followed an unusual design because the drug’s powerful mental effects make blinding versus a placebo nearly impossible. Roughly half the patients took two 25 mg doses of the drug three weeks apart. A quarter of the trial’s subjects received two doses of 10 mg, and another quarter two doses of 1 mg. Results showed a greater benefit with the highest dose than with the lowest at the six-week mark, as assessed by a commonly used measure of depression symptoms. Compass’ chief medical officer Guy Goodwin said the experience is “ often likened to a waking dream in that people have very intense perceptual, emotional and memory experiences, which can be literally regarded by some people who take it as the most significant experience of their life.” The trial will continue to evaluate the pill’s effectiveness at the six-month mark. Those results are expected in the summer. And Compass is hoping for a regulatory approval by the middle of next year. Read more from Elizabeth Cairns here. 🤝 Novartis is tapping into a macrocyclic peptide platform from Unnatural Products. The Swiss pharma giant will pay $100 million in upfront and pre-IND milestone payments, and Unnatural Products could get up to $1.7 billion in biobucks spread across development, regulatory and commercial milestones. Novartis will be in the driver’s seat for everything beginning at the IND-enabling stage, Kyle LaHucik reported. The progress of macrocyclic chemistry is “opening entirely new avenues in drug discovery,” Muneto Mogi, head of global discovery chemistry at Novartis Biomedical Research, said in a statement. Multiple startups are trying to pave those new avenues, including Danish contender Orbis Medicines, Boehringer Ingelheim-paired Circle Pharma, and Vilya, which was co-founded by Nobel Prize winner David Baker. DON’T MISS:

Novartis will pay $100 million in upfront and pre-IND milestone payments to tap into a macrocyclic peptide platform from Unnatural Products, a deal that could lead to new cardiovascular disease medicines. The move allows the Swiss pharma giant to delve into a niche but growing area of drug R&D that seeks to combine the precision and potency of biologics with the easier-to-use delivery of oral medicines. The progress of macrocyclic chemistry is “opening entirely new avenues in drug discovery,” said Muneto Mogi, head of global discovery chemistry at Novartis Biomedical Research. Those advances enable target engagement “at a dose and with a pharmacological versatility not possible with many other approaches,” he added in a Wednesday press release . Multiple startups are trying to pave those new avenues. That includes Danish contender Orbis Medicines , Boehringer Ingelheim- paired Circle Pharma, and Vilya , which was co-founded by Nobel Prize winner David Baker. Novartis’ bet could pay off big time for Unnatural Products. The startup could get up to $1.7 billion in biobucks spread across development, regulatory and commercial milestones. Novartis will be in the driver’s seat for everything beginning at the IND-enabling stage. Novartis joins companies like BridgeBio and Merck in tapping into Unnatural Products’ macrocyclic territory. Those partnerships have kept the biotech’s engine humming; it has not disclosed a funding round since its $32 million Series A in 2023. Unnatural Products CEO Cameron Pye said in an email to Endpoints News on Wednesday that the original Merck collaboration has “completed.” The company continues to “stay close” with the Merck Research Laboratories team and “have their continued partnership through their Global Health Innovation Fund,” Pye added. Unnatural Products’ pipeline was initially focused on oncology, but has shifted in recent years. At the time of its argenx deal announcement last year, Pye told Endpoints that Unnatural Products was working on an oral activin type 2 receptor antagonist. That area is drawing attention due to Eli Lilly’s bimagrumab , which seeks to promote fat loss while keeping muscle mass intact. Pye told Endpoints in the same email thread that Unnatural Products’ pipeline contains multiple programs, including a project in the field of obesity and metabolic diseases. He declined to disclose further details, including when the biotech could enter human trials. Pye co-founded Unnatural Products with chief scientific officer Joshua Schwochert in the final year of their PhD at UC Santa Cruz. Editor’s note: This story was updated to clarify the nature of the $100 million payment.

SOUTH SAN FRANCISCO, Calif--(BUSINESS WIRE)--Circle Pharma, Inc., a clinical-stage biopharmaceutical company pioneering next-generation targeted macrocycle therapeutics for cancer, today announced management will participate in upcoming investor conferences in February and March, as follows: Oppenheimer 36th Annual Healthcare Life Sciences Conference Presentation Date/Time: 3:20 p.m. ET, Wednesday, Feb. 25, 2026 Participants: David J. Earp, J.D., Ph.D., president and chief executive officer; Anne Borgman, M.D., chief medical officer; Rob Lauzen, chief financial officer Location: Virtual TD Cowen 46th Annual Health Care Conference Date: Monday, March 2, 2026 Participants: David J. Earp, J.D., Ph.D., president and chief executive officer; Anne Borgman, M.D., chief medical officer; Rob Lauzen, chief financial officer Location: Boston Leerink Global Healthcare Conference Date: Wednesday, March 11, 2026 Participants: David J. Earp, J.D., Ph.D., president and chief executive officer; Rob Lauzen, chief financial officer Location: Miami About Circle Pharma Circle Pharma is a clinical-stage biopharmaceutical company harnessing the power of macrocycles to develop next-generation targeted therapies for cancer. The company’s proprietary MXMO™ platform overcomes key challenges in macrocycle drug development, enabling the creation of intrinsically cell-permeable and orally bioavailable therapies, including for historically undruggable targets. Circle Pharma’s pipeline is focused on targeting cyclins, key regulators of the cell cycle that drive many cancers. The company’s lead program, CID-078, is a cyclin A/B RxL inhibitor in Phase 1 clinical development for patients with advanced solid tumors. Circle Pharma is based in South San Francisco, CA. For additional information, please visit us at circlepharma.com and follow us on LinkedIn and X . Contacts Media: Josie Butler, 1AB josie@1abmedia.com Investors: Rob Lauzen, Circle Pharma Robert.Lauzen@circlepharma.com