We are a clinical-stage biotechnology company developing next-generation injectable and oral nutrient stimulated hormone, or NuSH, analog peptides to treat obesity, overweight and related conditions. Obesity and overweight are among the fastest-growing and most prevalent chronic human conditions, affecting approximately 2.5 billion people worldwide, and drive a broad range of severe diseases. Currently approved NuSH analog peptides are a promising treatment option for obesity and overweight. However, the current treatment landscape exhibits several key limitations, including impediments to chronic therapy in large populations, such as administration by weekly injection, prolonged titration and tolerability issues; insufficient weight loss; lack of effective, well-tolerated oral dosing alternatives; and challenges in scaling manufacturing. We have developed and are implementing proprietary methods and platform technologies that we believe will allow us to develop and advance a broad, scalable and combinable portfolio of injectable and oral NuSH analog peptides with the potential to not only address the limitations of approved therapies, but also many of the anticipated limitations of next-generation therapies in development. We use our proprietary MINT peptide library of NuSH analog peptides alongside our Half-life Augmentation by Lipid Optimization, or HALO, half-life extending platform and our MOMENTUM oral NuSH analog peptide delivery platform to deliver highly differentiated product candidates that we are advancing into clinical trials for obesity or overweight. We believe our product candidates have the potential to reduce the barriers to adoption as a chronic therapy, while raising the ceiling of effectiveness, and improving manufacturing scalability. Our pipeline includes clinical-stage, injectable and oral glucagon-like peptide-1 receptor agonist, or GLP-1 RA, analog peptides, a clinical-stage injectable amylin analog, as well as multiple complementary preclinical NuSH analog peptides, such as an oral amylin analog, as well as glucose-dependent insulinotropic polypeptide, or GIP, glucagon and peptide YY, or PYY, analogs that we intend to develop for injection and we anticipate will be combinable with GLP-1 RAs. MET-097i, our most advanced product candidate, is a fully biased, monthly, subcutaneously injectable ultra-long acting GLP-1 RA that we are developing for the treatment of obesity and overweight. We have an ongoing Phase 1/2 clinical trial of MET-097i in the United States in participants who are obese or overweight but otherwise healthy. In September 2024, we announced preliminary results from Part A, the single ascending dose, or SAD, portion of the trial, and Part B, the multiple ascending dose, or MAD, portion of the trial, and in January 2025 we announced preliminary results from the Phase 2 (Part C) portion of the clinical trial. The preliminary data showed dose-linear pharmacokinetics, or PK, with a half-life of approximately 15 to 16 days. Mean placebo-adjusted body weight across the dose range in the Phase 2 part of the trial was 11.3% after twelve weekly doses of 1.2 mg and 7.2% after twelve weekly doses of 0.6 mg. In the MAD part of the trial, after five weekly doses of 1.2 mg, the mean change from baseline was 7.5% at day 36 (one week after the last dose), 8.1% at day 57 (four weeks after the last dose), and 7.5% at day 85 (eight weeks after the final dose), suggesting a durable pharmacodynamic, or PD, effect consistent with the observed half-life. Preliminary results of this clinical trial demonstrate that MET-097i was generally well-tolerated when dosed weekly as well as after a higher, potential monthly dose, with no treatment-related serious adverse events and no severe gastrointestinal adverse events. We have initiated a 28-week, double-blind, placebo-controlled Phase 2b clinical trial of MET-097i assessing safety and efficacy at different weekly doses in participants with obesity or overweight without type 2 diabetes, or T2D, and we expect to report preliminary data from this trial in mid 2025. We plan to separately initiate a Phase 2b study in participants with obesity or overweight with T2D. If successful, we plan to initiate a Phase 3 clinical program shortly thereafter in the United States and various countries in Europe. We also plan to initiate a Phase 2b clinical trial that will evaluate the efficacy and tolerability of multiple monthly doses of MET-097i after multiple weekly doses, for which we expect to report preliminary results by year-end 2025 or in early 2026. MET-097i is classified as a biologic and we intend to pursue its regulatory approval in the United States pursuant to a biologics license application, or BLA. MET-233i is a subcutaneously injectable ultra-long acting amylin analog, with enhanced solubility and miscibility with our other NuSH analog peptides, that we are developing for the treatment of obesity and overweight. We plan to develop MET-233i to be administered as a monotherapy or in combination with other NuSH analog peptides, including MET-097i. Based on preclinical studies and preliminary data from the SAD portion of our ongoing Phase 1 clinical trial in MET-233i, we believe the pharmacokinetics of MET-233i support the ability to combine it with MET-097. Our Investigational New Drug application, or IND, for a Phase 1 clinical trial of MET-233i monotherapy in patients with obesity or overweight was cleared by the U.S. Food and Drug Administration, or the FDA. We have initiated this trial in the United States and plan to report preliminary data in mid 2025. If we are able to establish sufficient evidence of clinical safety in our MET-233i Phase 1 trial, we plan to initiate a clinical trial of MET-097i in combination with MET-233i, also in the United States, for which we would expect to report preliminary data in late 2025. We have not yet initiated any clinical trials of a combined therapy. We believe this combination product candidate is likely to be reviewed by the FDA under a BLA. MET-224o is an oral, fully biased ultra-long acting GLP-1 RA that we are developing for the treatment of obesity and overweight. In vitro preclinical studies established MET-224oÕs potent and fully biased receptor activation activity. In in vivo head-to-head subcutaneous pharmacology studies, we have observed that MET-224o and MET-097i have shown similar effects on body weight loss and in pharmacokinetic studies we demonstrated promising exposure upon oral administration, suggesting the potential for injectable-like body weight loss with an oral therapy. In October 2024, our Clinical Trial Application, or CTA, was approved by Health Canada for a formulation optimization trial of our MOMENTUM oral peptide delivery platform using prototype compound MET-002, a predecessor peptide to MET-224o, and we have initiated dosing in that trial in Canada. In parallel to this formulation optimization trial, we plan to complete IND- and CTA-enabling studies of MET-224o, with a goal of allowing us to transition into a Phase 1/2 clinical trial of MET-224o that incorporates the learnings of the MET-002 formulation optimization trial. We expect to initiate this Phase 1/2 clinical trial at sites in the United States and/or Canada, and expect to report preliminary results in late 2025. We believe MET-224o will qualify as a biologic and we intend to pursue its regulatory approval in the United States pursuant to a BLA. In addition to these programs, we have preclinical programs that are advancing several other NuSH analog peptides targeting pathways complementary to the GLP-1 pathway, including an amylin analog for oral administration, as well as GIP, glucagon and PYY analogs for injection. We plan to initiate a variety of parallel combination clinical trials with these product candidates and MET-097i and MET-233i. We are also developing multiple oral and injectable unimolecular multi-receptor agonists which we believe will have a half-life similar to MET-097i, which are in preclinical development. We believe through these combinations, we may be able to raise the ceiling of effectiveness of obesity and overweight therapies, while further reducing barriers to chronic therapy and enhancing tolerability and manufacturing scalability. Our product candidates include potential drugs and potential biologics. In the United States, the FDA regulates drugs under the Federal Food, Drug, and Cosmetic Act, or the FDCA, and its implementing regulations, and biologics under the FDCA, the Public Health Service Act, or the PHSA, and their implementing regulations. The timing and requirements for seeking regulatory approval of a drug or a biologic are similar; however, marketing approval of a drug is typically pursued under a new drug application, or NDA, and marketing approval of a biologic is pursued under a BLA. We believe there are potential benefits inherent in the biologic pathway, including that biologics may be eligible for 12 years of reference product exclusivity, while a novel compound regulated as a drug may be eligible for a shorter period of exclusivity, and biologics may receive longer exclusion from price negotiations under the Inflation Reduction Act, or IRA. In each case, the submission of the NDA or BLA occurs after completion of the applicable pivotal trials. We were originally incorporated under the laws of the State of Delaware on June 29, 2022 under the name PHP Newco 1, Inc. We have two wholly owned subsidiaries, Zihipp Ltd. and Zihipp Inc. Our principal executive offices are located at 3 World Trade Center, 175 Greenwich Street, New York, New York.
