MBX-2109

Michele Rayes used to take 64 pills a day to manage her hypoparathyroidism, a rare endocrine disorder that impairs calcium levels, dampens daily quality of life and can sometimes lead to chronic kidney disease. Takeda’s Natpara wasn’t helping much. She continued experiencing a “3 o’clock crash” because of the drug’s short half-life and still relied on taking active vitamin D and what the patient community calls “rescue calcium.” After the Japanese drugmaker recalled Natpara due to manufacturing issues with rubber particulates, Rayes tried a new drug: Ascendis Pharma’s experimental daily injectable that replicates the natural parathyroid hormone in the body. Natpara “was a toy; it was kids’ play,” said Rayes, who’s had the condition for three decades and is now an associate director at the HypoPARAthyroidism Association, which receives industry funding. “I never felt like I had my life back. I never felt that change in quality of life.” This summer, the FDA approved the medicine, marketed as Yorvipath, and Rayes said she feels like she doesn’t “have a disease anymore,” saying she can now do daily activities that she hasn’t “done in decades.” Yorvipath’s approval is one of multiple milestones this year for the hypoparathyroidism market. “Clinical research has really intensified,” said Aliya Khan, a McMaster University endocrinologist who worked on Yorvipath’s late-stage trial and is the author of clinical guidelines . Over the last year, Ascendis snagged FDA approval for Yorvipath. AstraZeneca bought a biotech with a late-stage candidate. MBX Biosciences landed on the Nasdaq in September to help finance a mid-stage injectable. And Septerna went public in October to raise money to support what it believes is the first oral candidate to enter human studies. “You’re seeing the result of huge unmet need and a degree of innovation,” said Nicola Heffron, head of global marketing and market access at AstraZeneca’s Alexion. The condition is thought to be one of the most common rare diseases, affecting about 100,000 people in the US and also in Europe. It’s “the last classical hormone deficiency for which there is no hormone replacement,” according to Aimee Shu, a VP of clinical development at Ascendis, and has been “stuck in a rudimentary situation” compared to other conditions like type 1 diabetes. Multiple sources described the patient community as a vocal one. And the rise in R&D activity, coupled with growing awareness of the condition, could also lead to more diagnoses, said Patty Keating, the executive director of the HypoPARAthyroidism Association. She is also a patient who is participating in one of the blinded clinical trials. Patients can inherit the condition or can acquire it by way of disruptions to their thyroid glands during surgery. It impacts multiple organs, including the brain, bones, kidneys and intestines. Until recently, there have been few treatment options for patients aside from taking calcium and active vitamin D. It’s a “completely different” landscape today compared to five years ago, according to Keating. Since launching Yorvipath in Europe at the beginning of this year, Ascendis has seen a retention rate of about 99%, Ascendis CEO Jan Mikkelsen told Endpoints News . Yorvipath had an “encouraging” launch in Germany and Austria, Jefferies analyst Kelly Shi told investors in early September. More details about the launch are expected in the company’s quarterly earnings on Thursday. Ascendis plans for the treatment to be in more than 10 European countries next year, plus the US, where it set a wholesale acquisition cost of $285,000 per year. Rather than developing a prodrug like Ascendis, AstraZeneca is advancing a PTH receptor 1, or PTHR1, agonist that is also dosed daily. Dubbed eneboparatide, the investigational medicine aims to rid the need for calcium and vitamin D supplements while preserving bone mineral density, which is key for a patient population mainly comprising middle-aged women, according to AstraZeneca’s Heffron. The company got eneboparatide by way of its up to $1.05 billion acquisition of Amolyt Pharma in March. “There’s definitely a need for treatments that deal with the root cause,” Heffron said. “This condition doesn’t go away, so they need something that’s going to be sustainable.” AstraZeneca expects to have results from the Phase 3 trial in the first half of 2025, Heffron said. The small team at Amolyt was “quick off the blocks” in getting all the way to Phase 3, she said, and the UK drugmaker is now waiting with “bated breath” for the late-stage data. Behind Ascendis and AstraZeneca are MBX, Septerna and an earlier-stage private startup called Confo Therapeutics, which declined to disclose details on its preclinical PTHR1 agonist. MBX has a hormone replacement injectable, called MBX 2109 , in Phase 2 and expects to have topline results in the third quarter of 2025, MBX CEO Kent Hawryluk told Endpoints. The Indianapolis-area biotech went through a $163 million IPO in September to help advance the lead asset as well as a post-bariatric 
hypoglycemia peptide, a preclinical obesity drug and other programs. “We’re glad to see the progress in the space, the activity — most importantly for patients who really are in need of better treatments for hypoparathyroidism,” Hawryluk said. The company hopes its once-weekly option will be a more accessible one for patients versus taking daily drugs. MBX aims to commercialize the drug on its own in the US, but it could seek partners for other regions, he said. Septerna, meanwhile, entered a healthy volunteer study last month in Australia to test once- and twice-daily versions of its oral candidate called SEP-786. The startup has said it aims for Phase 1 data in mid-2025. After that, Septerna has said it will then test the PTH1R-targeting drug in Phase 2 in the US, Canada, Europe and other regions. “We think that the game-changer for this whole space will be an oral small molecule,” CEO Jeffrey Finer told Endpoints at the time of Septerna’s $150 million Series B in 2023. “We’ve developed compounds that we believe should work as well as those injectable peptides.”

Total gross proceeds from upsized initial public offering and Series C financing were approximately $251.2 million Last subject last visit in Phase 1 trial of MBX 1416 anticipated by late November; topline results to be reported in early January 2025 Enrollment of Phase 2 Avail™ trial of MBX 2109 in hypoparathyroidism on track to complete in Q1 2025; topline results anticipated in Q3 2025 Strong cash position, with $277.1 million expected to support operations into mid-2027 CARMEL, Ind., Nov. 07, 2024 (GLOBE NEWSWIRE) -- MBX Biosciences, Inc. (Nasdaq: MBX), a clinical-stage biopharmaceutical company focused on the discovery and development of novel precision peptide therapies for the treatment of endocrine and metabolic disorders, today reported financial results for the third quarter ended September 30, 2024, and highlighted recent progress. “The third quarter of 2024 has been transformational for MBX, as we transitioned to a publicly traded company and advanced our clinical-stage precision peptide programs,” said Kent Hawryluk, President and Chief Executive Officer of MBX Biosciences. “Our team is committed to delivering on our upcoming clinical milestones, including completion of the last subject visit in the Phase 1 trial of MBX 1416 anticipated by late November, and we expect to report top line results for this trial in early January 2025. In addition, enrollment in the Phase 2 trial of MBX 2109 in patients with hypoparathyroidism is on track to be complete in the first quarter of 2025, and we continue to expect topline results in the third quarter of 2025. The capital raised in our initial public offering in September and our Series C financing in August enables us to execute on these clinical milestones and advance the development of our early-stage pipeline programs, including our obesity portfolio, as we aim to overcome limitations of current therapies and improve the standard of care.” Third Quarter 2024 and Recent Business Highlights MBX 2109 Presented the rationale and design of the Phase 2 Avail™ trial of MBX 2109: In September 2024, the Phase 2 Avail trial of MBX 2109, the Company’s potential long-acting parathyroid hormone (PTH) peptide prodrug, in adults with hypoparathyroidism (HP) was featured in a poster presentation at the American Society for Bone and Mineral Research 2024 Annual Meeting held in Toronto, ON, Canada. Initiated Phase 2 Avail trial of MBX 2109: In August 2024, the Company announced that the first patient was dosed in the Phase 2 Avail trial of MBX 2109. Enrollment is expected to complete in the first quarter of 2025 with topline results expected in the third quarter of 2025. MBX 1416 Last Subject Last Visit in MBX 1416 Phase 1 trial anticipated by late November 2024: MBX expects the last subject visit to be completed by the end of November in the Phase 1 single and multiple ascending dose trial of MBX 1416, the Company’s long-acting glucagon-like peptide 1 (GLP-1) receptor antagonist in development for the treatment of post-bariatric hypoglycemia. The Company plans to announce topline results in early January 2025. MBX 4291 Progressing MBX 4291 IND-enabling studies: MBX is in the process of completing investigational new drug (IND) enabling studies for its GLP-1/GIP co-agonist prodrug MBX 4291 for the potential treatment of obesity and expects to submit an IND application to the U.S. Food and Drug Administration in the second quarter of 2025. The Company also has additional programs in the lead optimization stage of development for the treatment of obesity and associated comorbidities. Corporate Completed upsized initial public offering (IPO) and Series C financing: In September 2024, MBX completed its IPO following its Series C financing in August. Total gross proceeds from the Initial Public Offering and Series C financing were approximately $251.2 million. Third Quarter 2024 Financial Results Cash and Cash Equivalents and Marketable Securities: As of September 30, 2024, MBX had cash, cash equivalents and marketable securities of $277.1 million compared to $80.7 million as of December 31, 2023. Based on its current operating plan, management expects the combined cash, cash equivalents and marketable securities balance to fund operations into mid-2027. R&D Expenses: Research and development expenses for the three months ended September 30, 2024, were $16.7 million compared to $9.1 million for the same period in 2023. The increase of $7.7 million was driven by costs associated with ongoing IND-enabling studies for MBX 4291 and the ongoing MBX 2109 Phase 2 clinical trial. G&A Expenses: General and administrative expenses for the three months ended September 30, 2024, were $2.9 million compared to $1.9 million for the same period in 2023. The increase of $1.0 million was driven by increased personnel-related costs as the Company expanded its infrastructure to support its growth in operations. Net Loss: Net loss for the three months ended September 30, 2024, was $18.1 million compared to a net loss of $10.2 million for the same period in 2023. About MBX BiosciencesMBX Biosciences is a biopharmaceutical company focused on the discovery and development of novel precision peptide therapies based on its proprietary PEP™ platform, for the treatment of endocrine and metabolic disorders. The Company is advancing a pipeline of novel candidates for endocrine and metabolic disorders with clinically validated targets, established endpoints for regulatory approval, significant unmet medical needs and large potential market opportunities. The Company’s pipeline includes its lead product candidate MBX 2109, in Phase 2 development for the treatment of chronic hypoparathyroidism (HP); MBX 1416, in Phase 1 development for the treatment of post-bariatric hypoglycemia (PBH); and an obesity portfolio that includes MBX 4291, as well as multiple discovery and pre-clinical candidates in development for the treatment of obesity. The Company is based in Carmel, Indiana. To learn more, please visit the Company website at www.mbxbio.com and follow it on LinkedIn. About MBX’s Proprietary Precision Endocrine Peptide (PEP™) Platform MBX was founded by global leaders with a transformative approach to peptide drug design and development. Leveraging this expertise, the Company designed its proprietary Precision Endocrine Peptide™ (PEP™) platform to overcome the key limitations of unmodified and modified peptide therapies and to improve clinical outcomes and simplify disease management for patients. PEPs are selectively engineered to have optimized pharmaceutical properties, including extended time-action profiles and consistent drug concentrations with low peak-to-trough concentration ratios, consistent exposure to target tissues, and less frequent dosing. Forward-Looking StatementsThis press release contains “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, each as amended. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements include, but are not limited to, express or implied statements regarding: MBX Biosciences’ expectations regarding the Phase 2 Avail™ trial of MBX 2109, including the timing of patient enrollment and topline results, the Phase 1 trial of MBX 1416, including the timing of the last subject visit and topline results, IND-enabling studies in MBX 4291, including MBX Biosciences’ intention to submit an IND and the timing related thereto, and other product candidates in the lead optimization stage; and expectations regarding MBX Biosciences’ uses of capital, expenses and financial results, including the expected cash runway. Forward-looking statements are based on management’s current expectations and are subject to risks and uncertainties that could negatively affect MBX Biosciences’ business, operating results, financial condition and stock value. Factors that could cause actual results to differ materially from those currently anticipated include: risks relating to the Company’s research and development activities; MBX Biosciences’ ability to execute on its strategy including obtaining the requisite regulatory approvals on the expected timeline, if at all; uncertainties relating to preclinical and clinical development activities; the Company’s dependence on third parties to conduct clinical trials, manufacture its product candidates and develop and commercialize its product candidates, if approved; MBX Biosciences’ ability to attract, integrate and retain key personnel; risks related to the Company’s financial condition and need for substantial additional funds in order to complete development activities and commercialize a product candidate, if approved; risks related to regulatory developments and approval processes of the U.S. Food and Drug Administration and comparable foreign regulatory authorities; risks related to establishing and maintaining MBX Biosciences’ intellectual property protections; and risks related to the competitive landscape for MBX Biosciences’ product candidates; as well as other risks described in “Risk Factors,” in MBX Biosciences’ Registration Statement on Form S-1 filed with the Securities and Exchange Commission (SEC), as well as subsequent filings with the SEC. MBX Biosciences expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in its expectations or any changes in events, conditions or circumstances on which any such statement is based, except as required by law, and claims the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. MBX uses and intends to continue to use its Investor Relations website as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD. Accordingly, investors should monitor the Company’s Investor Relations website, in addition to following the Company’s press releases, SEC filings, public conference calls, presentations, and webcasts. Media Contact:Kate BurdickInizio Evoke Commskate.burdick@inizioevoke.com 860-462-1569 Investor Contact:Jim DeNikeMBX Biosciencesjdenike@mbxbio.com MBX BIOSCIENCES, INC. CONDENSED FINANCIAL INFORMATION (Unaudited) Condensed Statements of Operations Data: Three months ended September 30, Nine months ended September 30, (in thousands, except per share and per share data) 2024 2023 2024 2023 Operating expenses: Research and development $16,747 $9,073 $42,192 $20,807 General and administrative 2,865 1,872 7,392 4,513 Total operating expenses 19,612 10,945 49,584 25,320 Loss from operations (19,612) (10,945) (49,584) (25,320) Interest and other income, net 1,470 783 3,248 1,600 Net loss $(18,142) $(10,162) $(46,336) $(23,720) Net loss per common share, basic and diluted $(2.78) $(9.40) $(15.42) $(24.28) Weighted average number of common shares outstanding used in computation of net loss per common share, basic and diluted 6,515,616 1,081,349 3,004,382 976,824 Condensed Balance Sheet Data: September 30, December 31, (in thousands) 2024 2023 Cash, cash equivalents and marketable securities $277,063 $80,676 Working capital(1) 270,250 79,539 Total assets 282,400 84,180 Total liabilities 11,032 4,291 Convertible preferred stock - 152,357 Accumulated deficit (121,919) (75,583) Total stockholders equity (deficit) 271,368 (72,468) (1) Working capital is defined as total current assets less total current liabilities. See our financial statements and the related notes thereto included in our Quarterly Report on Form 10-Q for the Quarter Ending September 30, 2024 for further details regarding our current assets and current liabilities.