DKK1

Clinical data demonstrated treatment with AGA2118 resulted in dose-dependent increases in bone mineral densityWOODLAND HILLS, Calif., Sept. 30, 2024 (GLOBE NEWSWIRE) -- Angitia Biopharmaceuticals, a clinical-stage biotechnology company focused on the discovery and development of innovative therapeutics for serious musculoskeletal diseases, today announced data from its ongoing program evaluating AGA2118 for the treatment of osteoporosis, as presented at the American Society for Bone and Mineral Research 2024 Annual Meeting (ASBMR) on September 27-30, 2024, in Toronto, ON, Canada. Treatment with AGA2118, a bispecific antibody targeting both sclerostin and DKK1, led to rapid and durable increases in bone formation, decreases in bone resorption, and improvements in bone mineral density (BMD) and bone strength in humans and in animal models, as highlighted in multiple abstracts presented at the conference. “AGA2118 is the first clinical stage bispecific antibody to target two key regulators of bone metabolism, and our first-in-human data demonstrate clinical proof-of-concept for AGA2118,” said David Ke, M.D., Chairman and Chief Executive Officer of Angitia. “AGA2118 is well-tolerated and possesses a pharmacokinetic profile that has translated well to the clinic. In men and otherwise healthy postmenopausal women, we observed rapid and robust bone mineral density gains. We look forward to engaging regulators and continuing development in a diseased population.” In the first-in-human (FIH) trial, 88 men and otherwise healthy postmenopausal women, received AGA2118 or placebo (randomized 6:2) either subcutaneously or intravenously. Subjects were either dosed with a single dose of AGA2118 up to 15 mg/kg or multiple doses of AGA2118 up to 12mg/kg every 4 weeks for a total of three doses and were followed for 85 days in the single ascending dose (SAD) cohort or 169 days in the multiple ascending dose (MAD) cohort. AGA2118 was safe and well-tolerated at all dose levels tested, with adverse events balanced between treatment and placebo. No treatment-related serious adverse events (SAEs) were reported. In addition to safety, the Company observed clinical activity, including dose-dependent increases in bone formation markers P1NP, BSAP, and osteocalcin, as well as dose-dependent decreases in the bone resorption marker CTX-1. In both SAD and MAD cohorts, BMD increased from baseline in the lumbar spine, total hip, and femoral neck in a dose- and exposure-dependent manner. “The rapidity and robustness of the BMD and biomarker responses with AGA2118 in this first-in-human trial demonstrate the potential of AGA2118 to become an important new treatment option for patients with skeletal disease,” said Matthew Drake, M.D., Ph.D., Associate Professor of Medicine at the Mayo Clinic, Divisions of Endocrinology and Hematology. “In addition, the pharmacokinetics and safety of AGA2118 support further development.” The abstract and oral presentation outlining the FIH trial is entitled, “AGA2118, a Bispecific Antibody Neutralizing both Sclerostin and DKK1, Increased Bone Formation, Decreased Bone Resorption, and Led to Rapid BMD Gains in a First in Human, Single- and Multiple-Dose, Placebo-Controlled Randomized Study." Angitia made three additional presentations at ASBMR, including a second oral presentation and two posters. Those presentations summarize data from AGA2118 in a non-human primate (NHP) model of osteoporosis, AGA2118 pharmacokinetics (PK) in NHPs and humans, and long-term follow-up in NHPs treated with AGA2118. Results translated well from preclinical models to humans, and the PK profile of AGA2118 is supportive of future development. About Osteoporosis Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. Osteoporosis has become a global epidemic, especially for older women, due to an aging population and longer life expectancies. Estimates indicate that more than 200 million patients worldwide suffer from osteoporosis. Although there are a number of approved therapies for osteoporosis, limitations remain regarding the efficacy and/or safety of each of these options. Research also indicates that most severely osteoporotic individuals do not receive a bone-active agent. As a result, a large unmet medical need remains for the development of new osteoporosis therapies. About AGA2118 AGA2118 is a bispecific antibody that targets sclerostin and DKK1 and is in clinical development for the treatment of osteoporosis. Sclerostin and DKK1 are two critical, negative regulators of WNT signaling in osteoblasts and of bone metabolism. By targeting both proteins, AGA2118 is thought to prevent compensatory increase of either agent, aiming to improve the magnitude of bone mineral density gains in osteoporotic patients. Angitia wholly owns the bispecific antibody. About Angitia Biopharmaceuticals Angitia Biopharmaceuticals is a clinical-stage biotechnology company focused on the discovery and development of innovative therapeutics for serious musculoskeletal diseases. Angitia is currently studying 3 biologic product candidates in the clinic for the treatment of osteoporosis, osteogenesis imperfecta (OI), and spinal fusion. Leveraging the team's extensive experience and scientific acumen in novel drug development, Angitia is committed to providing groundbreaking therapies to satisfy key unmet medical needs. Learn more at www.angitiabio.com. Investor & Media Contact: William WindhamSolebury Strategic Communicationswwindham@soleburystrat.com646-378-2946 Forward-Looking Statements This press release is prepared by Angitia (the “Company”, “We”) for informational purposes only. Forward-looking statements include all statements that are not historical facts, and in some cases, can be identified by terms such as “anticipate”, “expect”, “intend”, “plan”, “believe”, “continue”, “could”, “potential”, “may”, “will”, “goal” or similar expressions and the negatives of those terms. However, not all forward-looking statements contain these identifying words. These forward-looking statements involve substantial known and unknown risks, uncertainties, and other factors that are beyond the Company’s control and are difficult to predict and may cause our actual results, timing of results, or achievements to be materially different from the information expressed or implied by these forward-looking statements. We anticipate that subsequent events and developments may cause our expectations and assumptions to change, and we undertake no obligation to update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise, except as may be required by law. Except as expressly required by law, the Company and/or its officers, directors, employees, and agents shall not assume responsibility for the accuracy and completeness of the forward-looking statements in the information provided.

Abstracts selected for 2 oral presentations and 2 poster presentations, including clinical and preclinical data setsWOODLAND HILLS, Calif., Sept. 16, 2024 (GLOBE NEWSWIRE) -- Angitia Biopharmaceuticals, a global, clinical-stage biotechnology company focused on the discovery and development of innovative therapeutics for serious musculoskeletal diseases, today announced that data from its ongoing program evaluating AGA2118 for the treatment of osteoporosis will be presented at the American Society for Bone and Mineral Research 2024 Annual Meeting (ASBMR) September 27-30, 2024, in Toronto, ON, Canada. Preclinical and clinical abstracts for AGA2118 were selected by conference organizers as highlights of the meeting. Details of the presentations are as follows: Title: AGA2118, a Bispecific Antibody Neutralizing both Sclerostin and DKK1, Increased Bone Formation, Decreased Bone Resorption, and Led to Rapid BMD Gains in a First in Human, Single- and Multiple-Dose, Placebo-Controlled Randomized StudyFormat: Oral PresentationSession Date and Time: Friday, Sept 27, 2024, 11:00 – 12:15 pm Abstract Number: 1011 Title: Long-Term Effects of AGA2118, a Bispecific Antibody that Neutralizes Both Sclerostin and DKK1, on Bone Formation and Bone Resorption Markers in Cynomolgus MonkeysFormat: Poster SessionSession Date and Time: Friday, Sept 27, 2024, 5:30 – 7:30 pm; Saturday, Sept 28, 2024, 2:15 – 3:45 pmAbstract Number: 109 Title: Preclinical and Clinical Pharmacokinetics of AGA2118, A Bispecific Antibody Neutralizing Both Sclerostin and Dickkopf-1 (DKK1), for the Treatment of OsteoporosisFormat: Poster SessionSession Date and Time: Saturday, Sept 28, 2024, 2:15 – 3:45 pmAbstract Number: 396 Title: AGA2118, a Bispecific Antibody Neutralizing Both Sclerostin and DKK1, Increased Bone Formation and Decreased Bone Resorption, Leading to a Rapid Increase in Bone Mass and Strength in an Ovariectomized Cynomolgus Monkey ModelFormat: Oral PresentationSession Date and Time: Sunday, Sept 29, 2024, 11:15 – 12:30 pmAbstract Number: 1071 About Osteoporosis Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. Osteoporosis has become a global epidemic, especially for older women, due to an aging population and longer life expectancies. Estimates indicate that more than 200 million patients worldwide suffer from osteoporosis. Although there are a number of approved therapies for osteoporosis, limitations remain regarding the efficacy and/or safety of each of these options. Research also indicates that most severely osteoporotic individuals do not receive a bone-active agent. As a result, a large unmet medical need remains for the development of new osteoporosis therapies. About AGA2118 AGA2118 is a Sclerostin x DKK1 bispecific antibody in clinical development for the treatment of osteoporosis. Sclerostin and DKK1 are two critical, negative regulators of WNT signaling in osteoblasts and bone metabolism. By targeting both proteins, AGA2118 is thought to prevent compensatory increase of either agent, aiming to improve magnitude of bone mineral density gains in osteoporotic patients. Angitia wholly owns the bispecific antibody. About Angitia Biopharmaceuticals Angitia Biopharmaceuticals is a clinical-stage biotechnology company focused on the discovery and development of innovative therapeutics for serious musculoskeletal diseases. Angitia is currently studying 3 biologic product candidates in the clinic for the treatment of osteoporosis, osteogenesis imperfecta (OI), and spinal fusion. Leveraging the team's extensive experience and scientific acumen in novel drug development, Angitia is committed to providing groundbreaking therapies to satisfy key unmet medical needs. Learn more at www.angitiabio.com. Investor & Media Contact: William WindhamSolebury Strategic Communicationswwindham@soleburystrat.com646-378-2946 Forward-Looking Statements This press release is prepared by Angitia (the “Company”, “We”) for informational purposes only. Forward-looking statements include all statements that are not historical facts, and in some cases, can be identified by terms such as “anticipate”, “expect”, “intend”, “plan”, “believe”, “continue”, “could”, “potential”, “may”, “will”, “goal” or similar expressions and the negatives of those terms. However, not all forward-looking statements contain these identifying words. These forward-looking statements involve substantial known and unknown risks, uncertainties, and other factors that are beyond the Company’s control and are difficult to predict and may cause our actual results, timing of results, or achievements to be materially different from the information expressed or implied by these forward-looking statements. We anticipate that subsequent events and developments may cause our expectations and assumptions to change, and we undertake no obligation to update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise, except as may be required by law. Except as expressly required by law, the Company and/or its officers, directors, employees, and agents shall not assume responsibility for the accuracy and completeness of the forward-looking statements in the information provided.

CAMBRIDGE, Mass., Aug. 12, 2024 /PRNewswire/ -- Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, today reported financial results for the second quarter ended June 30, 2024. Leap Highlights: Overall response rate (ORR) increases to 33% across all evaluable patients and 38% across evaluable patients with left-sided CRC in updated data from Part A of the Phase 2 DeFianCe study evaluating DKN-01 in combination with bevacizumab and chemotherapy in second-line patients with advanced colorectal cancer (CRC) Expanded the randomized controlled Part B of the DeFianCe study to 180 patients; enrollment expected to be completed by end of September 2024 with data expected in mid-2025 Patient follow-up continues in the randomized controlled Part C of the Phase 2 DisTinGuish study evaluating DKN-01 in combination with tislelizumab and chemotherapy in first-line patients with advanced gastroesophageal junction (GEJ) and gastric cancer; data expected in Q4 2024 or early 2025 Completed $40 million private placement with new and existing investors, including Gilead Sciences, Inc. "With the momentum provided by our $40 million private placement, we are positioned to achieve our critical company milestones," said Douglas E. Onsi, President and Chief Executive Officer of Leap. "We have executed well on our two DKN-01 randomized controlled trials and on preparatory activities for registrational studies. We look forward to sharing initial data from both randomized controlled studies over the next 12 months as we strive to deliver new treatments for patients fighting against cancer." DKN-01 Development Update ORR increases in updated data from Part A of the DeFianCe Study . The DeFianCe study (NCT05480306) is a Phase 2 study evaluating DKN-01 in combination with bevacizumab and chemotherapy in second-line patients with advanced microsatellite stable CRC. Preliminary results from Part A of the study were previously reported at the 2024 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium in January 2024. In April 2024, a ninth Part A patient was identified as having a partial response (PR). This patient, who has left-sided Consensus Molecular Subtype 4 CRC with APC and TP53 mutations and KRAS wildtype genetics, had been previously treated with cetuximab and chemotherapy. The patient enrolled in Part A in March 2023 and had a best response of stable disease (SD) for over a year before the tumor reduction deepened into a PR. The patient remains on study with a confirmed PR. Key Updated Part A Findings (as of June 7, 2024 data cut-off) : Across all patients enrolled (n=33): ORR among response-evaluable patients (n=27) was 33% and disease control rate (DCR) was 93%, including 9 PRs and 16 patients with a best response of SD Median progression-free survival (PFS) was unchanged at 6.3 months Enhanced activity in patients with left-sided tumors (n=25), a group that has more frequent activation of the Wnt pathway modulated by DKK1 38% ORR and 100% DCR in response-evaluable population (8 PRs, 13 SDs) Median PFS was unchanged at 8.6 months DKN-01 plus bevacizumab and chemotherapy was well-tolerated, with a majority of DKN-01 related events being low grade (Grade 1/2) Enrollment in Part B of the DeFianCe Study in CRC patients is ongoing and expected to be completed by the end of September 2024. The Company expanded the randomized controlled Part B of the DeFianCe study from 130 to 180 patients and included PFS in the subpopulation of patients with left-sided CRC as an additional primary endpoint. As of August 9, 2024, 161 patients have enrolled in Part B. The Company expects to complete enrollment by the end of September 2024, with data expected mid-2025. Randomized controlled Part C of the DisTinGuish study in patients with GEJ and gastric cancer is ongoing, with initial data expected in Q4 2024 or early 2025. The DisTinGuish study (NCT0436380) is a Phase 2, randomized, open-label, multicenter study of DKN-01 in combination with tislelizumab and chemotherapy in first-line, HER-2 negative patients with GEJ and gastric cancer. Part C enrolled 170 patients randomized 1:1 to evaluate DKN-01 in combination with tislelizumab and chemotherapy, compared to tislelizumab and chemotherapy alone. The Company expects to report initial data from Part C of the DisTinGuish study in Q4 2024 or early 2025. Business Update: Completed a $40 million private placement. In April 2024, Leap entered into a securities purchase agreement with a select group of new and existing investors including Gilead Sciences, Inc., a life sciences-focused investor, Samsara BioCapital, LP, 683 Capital Partners, LP, Laurion Capital Management LP, and Rock Springs Capital Management LP. Gross proceeds from the private placement were approximately $40 million. The net proceeds from this financing, combined with existing cash, cash equivalents and marketable securities, are expected to fund Leap's operating and capital expenditures into the second quarter of 2026. Selected Second Quarter 2024 Financial Results Net Loss was $20.4 million for the second quarter 2024, compared to $13.4 million for the same period in 2023. The increase was primarily due to an increase in research and development expenses. Research and development expenses were $17.9 million for the second quarter 2024, compared to $11.1 million for the same period in 2023. The increase of $6.8 million was primarily due to an increase of $5.7 million in clinical trial costs due to patient enrollment, the duration of patients on study, the enhancement of correlative studies, increase in site activity associated with Part C of the DisTinGuish study, and the expansion of the size of Part B of the DeFianCe study. There was also an increase of $0.6 million in manufacturing costs related to clinical trial material and manufacturing campaigns and an increase of $0.5 million in payroll and other related expenses due to an increase in headcount of our R&D full-time employees. General and administrative expenses were $3.4 million for the second quarter 2024, compared to $3.6 million for the same period in 2023. The decrease was due to a decrease of $0.3 million in professional fees associated with our business development activities, partially offset by a $0.1 million increase in payroll and other related expenses. Cash and cash equivalents totaled $78.5 million at June 30, 2024. About Leap Therapeutics Leap Therapeutics (Nasdaq: LPTX) is focused on developing targeted and immuno-oncology therapeutics. Leap's most advanced clinical candidate, DKN-01, is a humanized monoclonal antibody targeting the Dickkopf-1 (DKK1) protein. DKN-01 is being developed in patients with esophagogastric, gynecologic, and colorectal cancers. FL-301, is a humanized monoclonal antibody targeting Claudin18.2, being developed in patients with gastric and pancreatic cancer. Leap also has preclinical antibody programs targeting Claudin18.2/CD137 and GDF15. For more information about Leap Therapeutics, visit or view our public filings with the SEC that are available via EDGAR at or via . FORWARD-LOOKING STATEMENTS This press release contains forward-looking statements within the meaning of the federal securities laws. Such statements are based upon current plans, estimates and expectations of the management of Leap that are subject to various risks and uncertainties that could cause actual results to differ materially from such statements. The inclusion of forward-looking statements should not be regarded as a representation that such plans, estimates and expectations will be achieved. Words such as "anticipate," "expect," "project," "intend," "believe," "may," "will," "should," "plan," "could," "continue," "target," "contemplate," "estimate," "forecast," "guidance," "predict," "possible," "potential," "pursue," "likely," and words and terms of similar substance used in connection with any discussion of future plans, actions or events identify forward-looking statements. All statements, other than historical facts, including statements regarding the potential safety, efficacy, and regulatory and clinical progress of Leap's product candidates; the anticipated timing for completion of clinical trials and release of clinical trial data and the expectations surrounding the outcomes thereof; Leap's future clinical or preclinical product development plans for any of Leap's product candidates; Leap's estimations of projected cash runway; and any assumptions underlying any of the foregoing, are forward-looking statements. Important factors that could cause actual results to differ materially from Leap's plans, estimates or expectations could include, but are not limited to: (i) Leap's ability to successfully execute its clinical trials and the timing of enrollment in and cost of such clinical trials; (ii) the results of Leap's clinical trials and pre-clinical studies; (iii) Leap's ability to successfully enter into new strategic partnerships for DKN-01 or any of its other programs and to maintain its ongoing collaborations with BeiGene, NovaRock and Adimab; (iv) whether any Leap clinical trials and products will receive approval from the U.S. Food and Drug Administration or equivalent foreign regulatory agencies; and (v) exposure to inflation, currency rate and interest rate fluctuations, as well as fluctuations in the market price of Leap's traded securities. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Leap may not actually achieve the forecasts disclosed in such forward-looking statements, and you should not place undue reliance on such forward-looking statements. Such forward-looking statements are subject to a number of material risks and uncertainties including but not limited to those set forth under the caption "Risk Factors" in Leap's most recent Annual Report on Form 10-K filed with the SEC, as well as discussions of potential risks, uncertainties, and other important factors in its subsequent filings with the SEC. Any forward-looking statement speaks only as of the date on which it was made. Neither Leap, nor any of its affiliates, advisors or representatives, undertake any obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law. These forward-looking statements should not be relied upon as representing Leap's views as of any date subsequent to the date hereof. CONTACT: Douglas E. Onsi President & Chief Executive Officer Leap Therapeutics, Inc. 617-714-0360 [email protected] Matthew DeYoung Investor Relations Argot Partners 212-600-1902 [email protected] SOURCE Leap Therapeutics, Inc.