Fractures, Multiple

Prioritizing and focusing on highest-value opportunities NC410 (ovarian and CRC) and LNCB74 (B7-H4 ADC)Based on early evidence of clinical activity with NC410 combo, expanding ovarian and CRC cohorts with data updates in 2024LNCB74, in collaboration with LegoChem, planned filing of an IND by year-end 2024Restructuring of our operations, including a reduction in workforce to better align resources toward prioritized programs Cash of approximately $108 million, combined with the restructuring, now expected to fund operations into the second half of 2026 BELTSVILLE, Md. – March 21, 2024, March 21, 2024 (GLOBE NEWSWIRE) -- NextCure, Inc. (Nasdaq: NXTC), a clinical-stage biopharmaceutical company committed to discovering and developing novel, first-in-class and best-in-class therapies to treat cancer today provided a business update and reported full year 2023 financial results. “Clinical data generated in 2023 enabled us to objectively assess each program and set our priorities for 2024. Based on that assessment, we will prioritize NC410 combo and LNCB74 in 2024, while seeking to partner our other portfolio assets," said Michael Richman, NextCure’s president and chief executive officer. “These strategic decisions have led to restructuring our workforce reflecting our reduced need for internal GMP manufacturing operations. We believe we have sufficient inventory to support our currently planned clinical trials. I wish to thank those employees who are impacted today for their contributions and dedication to our mission.” Mr. Richman continued, “We are excited to focus on NC410 combo, which is demonstrating clinical responses in ovarian and colorectal cancers. We are advancing LNCB74 in collaboration with LegoChem Biosciences, a differentiated ADC directed to B7-H4, a clinically validated cancer target. Given our current cash position and revised runway to the second half of 2026, we believe we can advance our two programs through important near-term clinical milestones.” Business Highlights and Near-Term Milestones Prioritized Programs NC410 (LAIR-2 fusion) The multi-center, multi-arm, first-in-human Phase 1b combination trial is evaluating the efficacy of NC410 in combination with pembrolizumab. Indications include: (i) ICI Naïve and refractory ovarian cancer and (ii) microsatellite stable (MSS) / microsatellite instability low (MSI-L) immune checkpoint inhibitor (ICI) Naïve and refractory colorectal cancer (CRC). The combination has been shown to be well tolerated up to 200 mg of NC410 with Grade 3 or higher Treatment Related Adverse Events of 3.7%. NC410 for Ovarian Cancer Evidence of early clinical activity and biomarker observations support the proposed mechanism of action for NC410 in relapsed/refractory ICI Naïve ovarian cancer, with/without active liver metastasis for subjects in the 100 mg and 200 mg cohorts. As of February 23, 2024, the findings of the initial 7 evaluable patients based on RECIST 1.1 are summarized in the table below: Relapsed/Refractory ICI Naïve Ovarian, 100 mg and 200 mg cohorts Evaluable Patients as of February 23, 2024n=7Overall Response rate (ORR)42.8%, n=3Disease Control Rate (DCR)42.8%, n=3Evidence supporting mechanism of actionObserved in biomarker data Additional observations from the initial 7-patient data set as of February 23, 2024, include: 3 partial responses (PR) were observed at the initial 9-week scan.1 confirmed PR observed in the 200 mg cohort continues on study beyond 6 months.The 2 PRs at the 100 mg cohort are pending confirmatory scans at week 18. Biomarker data on blood samples drawn from patients in both the prior NC410 monotherapy trial and, the current NC410 combo trial support our hypothesis regarding the mechanism of action (MOA) and activity in PR patients as follows: Decrease in peripheral Granzyme B-expressing CD8+ T cells, which supports our mechanism of action (MOA) that NC410 remodels the extracellular matrix (ECM) allowing activated immune cells to infiltrate into the tumor microenvironment (TME). Generation of collagen-derived product 4GZ fragments is mediated by Granzyme B-expressing T cells and provides direct evidence of ECM remodeling and correlates with responses.Decrease in peripheral myeloid-derived suppressor cells reduces suppressive effects and enhances activation of immune cells and anti-tumor activity.Decrease in peripheral CCR7+ DC+ T cells which is consistent with chemokine guided migration of immune cells to the TME. Taken together, the data demonstrate that NC410 mediates activation of immune cells and migration into the TME through remodeling of the ECM. We believe NC410 combo results in anti-tumor activity and clinical responses in patients that have been shown to respond poorly to or are resistant to checkpoint inhibitors.In March 2024, we commenced enrolling an additional 18 patients among the 100 mg and 200 mg cohorts. We plan to present the data from the ovarian cancer patients in the second half of 2024. NC410 Colorectal Cancer (CRC) Preliminary evidence of clinical activity in the 100 mg cohort of patients with MSS/ MSI-L ICI naïve CRC without active liver metastasis (LM-). The findings as of February 23, 2024, of the initial 19 evaluable patients are summarized based on RECIST 1.1 guideline in the table below: MSS/MSI-L ICI Naïve CRC, LM-, 100 mg cohort Evaluable Patients as of February 23, 2024n=19Overall Response rate (ORR)10.5%, n=2Disease Control Rate (DCR)47.3%, n=9Median Progression Free Survival (mPFS)8.1 months Additional observations from the 19-patient data set as of February 23, 2024: Both responses were observed at the initial 9-week scan in the 100 mg cohort.Subjects enrolled had a median of 5 lines of prior treatment.The 2 responders remain as PRs, and continue on study for over 10 months and 5 months, respectively. Completed enrollment in January 2024 of an additional 20 patients in the 100 mg cohort. We plan to present the data of the CRC patients at a scientific conference within the second quarter of 2024. LNCB74 (B7-H4 ADC) Selected our first antibody drug conjugate (ADC) candidate of a potential of three from our collaboration with LegoChem Biosciences, Inc. (LegoChem). Under the terms of the Agreement, both parties equally share the costs of developing the molecules and profits on commercialized products.Commenced development of LNCB74 utilizing a NextCure B7-H4 antibody and LegoChem's ConjuAllTM ADC technology.Differentiated approach leveraging: B7-H4 specific antibody with an Fc modification that protects immune cells to improve safetyUse of a glucuronidase cleavable linker that offers cancer-selective payload release to minimize toxicity in non-tumor cells, andUse of a monomethyl auristatin E (MMAE) payload with a drug-to-antibody ratio (DAR) of 4, that has the advantage of bystander killing of surrounding tumor cells. Pre-clinical experiments in vitro and in vivo demonstrating potent tumor killing and pilot toxicology studies have been completed.Pre-filing feedback from the FDA supports moving forward to planned submission of an IND application by this year-end.Ongoing activities associated with GLP toxicity studies, GMP manufacturing, and clinical development planning are in progress. Assets We Intend to Partner NC525 is a novel LAIR-1 antibody that selectively targets Acute Myeloid Leukemia (AML) blast cells and leukemic stem cells, and currently is in a Phase 1a monotherapy dose escalation and safety study evaluating NC525 in AML patients. The trial is now in the fifth dose escalation cohort, and we plan to complete the dose-finding portion of the study to arrive at a predicted biologically active dose and further assess development plans by the fourth quarter of 2024.NC605 is an antibody that targets Siglec-15 and has the potential as a treatment for bone disease. Preclinical data show that NC605 treatment reduced bone loss and enhanced bone quality in mice with osteogenesis imperfecta (OI). OI is a rare disorder that results in high bone turnover, abnormal bone formation, bone fragility, and recurrent fractures. NC605 could also have applications in chronic bone diseases such as osteoarthritis and non-union fractures. We are currently conducting toxicology studies in preparation for partnering.NC181 is a humanized antibody targeting ApoE4 for the treatment of Alzheimer’s disease (AD). In preclinical AD animal models, NC181 has demonstrated amyloid clearance, prevention of amyloid deposition, plaque clearance and neuroinflammation reduction. Preclinical studies have demonstrated that it reduces microhemorrhages, improves cerebral vascular function and lowers risk of Amyloid Related Imaging Abnormalities (ARIA). Restructuring of Operations Implemented a restructuring plan to reduce operating costs and better align our workforce with the needs of our business. Under the plan, we paused our internal manufacturing operations and reduced our workforce by approximately 37%. We estimate that we will incur one-time restructuring charges of approximately $0.8 million including employee severance, benefits and related termination costs, the majority of which we expect to pay in the second quarter of 2024. Financial Guidance NextCure expects its existing cash, cash equivalents and marketable securities will enable it to fund operating expenses and capital expenditures into the second half of 2026. Financial Results for Full Year Ended December 31, 2023 Cash, cash equivalents, and marketable securities as of December 31, 2023, were $108.3 million as compared to $159.9 million as of December 31, 2022. The decrease of $51.6 million was primarily due to cash used to fund operations, and cash used to purchase fixed assets.Research and development expenses were $47.9 million for the year ended December 31, 2023, as compared to $54.2 million for the year ended December 31, 2022. The decrease of $6.3 million was primarily due to lower costs related to our clinical programs.General and administrative expenses were $19.7 million for the year ended December 31, 2023, as compared to $21.7 million for the year ended December 31, 2022. The decrease of $2.0 million was primarily related to lower personnel-related costs, including $1.2 million of stock compensation, and lower insurance and professional costs.Net loss was $62.7 million for the year ended December 31, 2023, as compared with a net loss of $74.7 million for the year ended December 31, 2022. Lower research and development expenses, lower general and administrative expenses and higher other income contributed to the lower net loss. About NextCure, Inc. NextCure is a clinical-stage biopharmaceutical company that is focused on advancing innovative medicines that treat cancer patients that do not respond to, or have disease progression on, current therapies, through the use of differentiated mechanisms of actions including antibody-drug conjugates, antibodies and proteins. We focus on advancing therapies that leverage our core strengths in understanding biological pathways and biomarkers, the interactions of cells, including in the tumor microenvironment, and the role each interaction plays in a biologic response. www.nextcure.com Forward-Looking Statements Some of the statements contained in this press release are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including with respect to funding for our operations, objectives and expectations for our business, operations and financial performance and condition, including the progress and results of clinical trials, development plans and upcoming milestones regarding our therapies. Any statements contained herein that are not statements of historical fact may be deemed to be forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as “aim,” “anticipate,” “assume,” “believe,” “continue,” “could,” “should,” “due,” “estimate,” “expect,” “intend,” “hope,” “may,” “objective,” “plan,” “predict,” “potential,” “positioned,” “seek,” “target,” “towards,” “forward,” “later,” “will,” “would” and other similar expressions that are predictions of or indicate future events and future trends, or the negative of these terms or similar language. Forward-looking statements involve substantial risks and uncertainties that could cause actual results to differ materially from those projected in any forward-looking statement. Such risks and uncertainties include, among others: positive results in preclinical studies may not be predictive of the results of clinical trials; NextCure’s limited operating history and not having any products approved for commercial sale; NextCure’s history of significant losses; NextCure’s need and ability to obtain additional financing on acceptable terms or at all; risks related to clinical development, marketing approval and commercialization; and NextCure’s dependence on key personnel. More detailed information on these and additional factors that could affect NextCure’s actual results are described under the heading “Risk Factors” in NextCure’s most recent Annual Report on Form 10-K and in NextCure’s other filings with the Securities and Exchange Commission. You should not place undue reliance on any forward-looking statements. Forward-looking statements speak only as of the date of this press release, and NextCure assumes no obligation to update any forward-looking statements, even if expectations change. Selected Financial Information Selected Statement of Operations Items: Year Ended December 31(in thousands, except share and per share amounts) 2023 2022Operating expenses: Research and development $47,931 $54,199 General and administrative 19,706 21,710 Loss from operations (67,637) (75,909)Other income, net 4,914 1,176 Net loss $(62,723) $(74,733)Net loss per common share - basic and diluted $(2.25) $(2.69)Weighted-average shares outstanding - basic and diluted 27,836,584 27,744,209 Selected Balance Sheet Items: December 31, December 31, (in thousands) 2023 2022 Cash, cash equivalents, and marketable securities $108,299 $159,911 Total assets $128,038 $184,161 Accounts payable and accrued liabilities $6,883 $9,127 Total stockholders' equity $114,421 $167,530 Investor InquiriesTimothy Mayer, Ph.D.NextCure, Inc.Chief Operating Officer(240) 762-6486IR@nextcure.com

Data Presented at the 2023 American Society for Bone and Mineral Research (ASBMR) Annual MeetingBELTSVILLE, Md., Oct. 17, 2023 (GLOBE NEWSWIRE) -- NextCure, Inc. (Nasdaq: NXTC), a clinical-stage biopharmaceutical company committed to discovering and developing novel, first-in-class immunomedicines to treat cancer and other immune-related diseases, today announced the presentation of new preclinical data demonstrating that treatment with NC605, a novel anti-Siglec-15 (S15) antibody, reduced bone loss and enhanced bone quality in mice with osteogenesis imperfecta (OI), at the 2023 American Society for Bone and Mineral Research (ASBMR) annual meeting. These results support development of NC605 as a potential highly effective treatment for osteogenesis imperfecta, a rare disease in which bones easily fracture. Osteogenesis imperfecta is a rare disorder that results in high bone turnover, abnormal bone formation, bone fragility and recurrent fractures. There is no cure for OI and current anti-resorptive treatments increase bone mineral density (BMD) primarily by inhibiting bone loss; however, these agents also inhibit bone formation. Unlike anti-resorptive therapies, NC605 enhances osteoblast recruitment, resulting in overall enhanced bone quality. In preclinical testing, NC605 has been shown to prevent bone loss by inhibiting osteoclast maturation and bone resorption by binding S15, which is expressed on the cell surface of immature osteoclasts and upregulated in differentiated osteoclasts. NextCure identified NC605 while screening S15 antibodies for anticancer properties. Further characterization revealed that the S15 antibodies without anticancer properties had the ability to inhibit osteoclast maturation and thus may have use in treating bone disease. The number of new bone fractures and bone quality were assessed and compared to control animals and to female OI mice (oim) from a prior study. Key findings include: Treatment with the surrogate antibody, NP159 prevented new bone fractures in 90% of male oim compared to 85% of female oim seen earlier. All control mice had one or more new bone fractures.High resolution microCT showed decreased trabecular bone separation with NP159 treatment in both oim males and females (p=0.05).Cortical bone porosity, a measure of mechanical strength of bone, was normal in the treated male mice, in contrast with females who showed increased porosity.There were no changes in the overall bone mineral density for male or female mice.Bone stiffness increased in both male and female oim.Fourier Transform Infrared (FTIR-I) readouts, a measure of bone quality, in treated females showed a normalization of mineral: matrix ratio, increased acid phosphate and decreased collagen maturity. Interestingly and in contrast, the males showed no similar changes. “We previously demonstrated that the surrogate antibody, NP159 (murine mAb parent to NC605) improved bone quality and decreased fractures in female oim. To address potential differences in therapeutic effects given sexual dimorphism seen with OI, we have now extended the study to evaluate and demonstrate efficacy in male oim,” said Solomon Langermann, Ph.D., NextCure’s chief scientific officer. “Given the unique properties of NC605 to improve bone quality, and reduce fractures, coupled with its safe profile, NC605 holds great promise as a potential transformative agent needed to provide treatment for OI patients throughout their life, including both female and male patients.” The data were generated in collaboration with Dr. Cathleen Raggio, Hospital for Special Surgery, New York. The data were presented in a poster presentation by Dr. Raggio at the 2023 American Society for Bone and Mineral Research. Title: Sexual Dimorphism in Treatment Effect of Anti-Siglec 15 in Adult Mice with Moderate-to-Severe Osteogenesis ImperfectaAbstract No: LB SUN-655 About NextCure, Inc.NextCure is a clinical-stage biopharmaceutical company committed to discovering and developing novel, first-in-class immunomedicines to treat cancer and other immune-related diseases. Through our proprietary FIND-IO™ platform, we study various immune cells to discover and understand targets and structural components of immune cells and their functional impact in disease in order to develop immunomedicines. Our focus is to bring hope and new treatments to patients who do not respond to current cancer therapies, patients whose cancer progresses despite treatment and patients with cancer types not adequately addressed by available therapies. http://www.nextcure.com Cautionary Statement Regarding Forward-Looking StatementsStatements made in this press release that are not historical facts are forward-looking statements. Words such as “expects,” “believes,” “intends,” “hope,” “forward” and similar expressions are intended to identify forward-looking statements. Examples of forward-looking statements in this press release include, among others, statements about NextCure’s plans, objectives, and intentions with respect to the discovery of immunomedicine targets and the discovery and development of immunomedicines. Forward-looking statements involve substantial risks and uncertainties that could cause actual results to differ materially from those projected in any forward-looking statement. Such risks and uncertainties include, among others: our limited operating history and no products approved for commercial sale; our history of significant losses; our need to obtain additional financing; risks related to clinical development, including that early clinical data may not be confirmed by later clinical results; risks that pre-clinical research may not be confirmed in clinical trials; risks related to marketing approval and commercialization; and the unproven approach to the discovery and development of product candidates based on our FIND-IO platform. More detailed information on these and additional factors that could affect NextCure’s actual results are described in NextCure’s filings with the Securities and Exchange Commission (the “SEC”), including NextCure’s most recent Form 10-K and subsequent Form 10-Q. You should not place undue reliance on any forward-looking statements. NextCure assumes no obligation to update any forward-looking statements, even if expectations change. Investor InquiriesTimothy Mayer, Ph.D.NextCure, Inc.Chief Operating Officer(240) 762-6486IR@nextcure.com

Ilofotase alfa demonstrates pharmacologically relevant effect on disease specific biomarkers and a positive safety pro adult patients with hypophosphatasia; Data to be presented by Lothar Seefried, MD, at the American Society for Bone and Mineral Research’s Symposium on Rare Bone Diseases on Thursday, October 12, 2023 UTRECHT, The Netherlands--(BUSINESS WIRE)-- AM-Pharma B.V. today announced positive clinical results from the Phase 1b study evaluating the company’s proprietary recombinant alkaline phosphatase, ilofotase alfa, as potential enzyme replacement therapy in adult hypophosphatasia (HPP) patients. HPP is an inherited metabolic disease, characterized by low activity of tissue non-specific alkaline phosphatase (TNAP), caused by mutations at the ALPL gene. This low activity leads to accumulation of inorganic pyrophosphate (PPi), a strong inhibitor of mineralization, as well as pyridoxal-5’-phosphate (PLP), an important cofactor for enzymes. The disease can range widely in severity, however most adults with HPP suffer from recurrent fractures, muscle weakness, joint diseases and pain.1 In the open-label pilot trial, a total of 12 patients were randomly assigned to one of two treatment arms and received a single intravenous dose of either 0.8 mg/kg or 3.2 mg/kg. Patients were followed for 10 days after dosing to evaluate changes in the biochemical fingerprint of HPP, safety and tolerability. The primary objectives for the study were changes in serum levels of PLP and PPi as compared to baseline. For PLP, the maximum proportional reduction was 35% in the 0.8 mg/kg cohort and 66% in the 3.2 mg/kg cohort. The mean time to return to 90% of baseline was 55 hours in the low-dose cohort and 168 hours in the high-dose cohort. The maximal proportional reduction for PPi was 36% in the 0.8 mg/kg cohort and 77% in the 3.2 mg/kg cohort. The mean time to return to 90% of baseline was 9.3 hours in the low-dose cohort and 53 hours in the high-dose cohort. In addition, ilofotase alfa was well-tolerated with pharmacokinetics consistent with observations from previous clinical studies. “The pronounced effect on all HPP disease relevant biomarkers together with a positive safety and tolerability profile, consistent with previous clinical studies with ilofotase alfa, supports its further development as a treatment option for adult HPP patients who are currently underserved,” said Juliane Bernholz, PhD, Chief Executive Officer of AM-Pharma. The full dataset will be presented at the American Society for Bone and Mineral Research – Rare Bone Disease Alliance (ASBMR-RBDA) Symposium at the Vancouver Convention Centre in Vancouver, BC, Canada. The presentation by Lothar Seefried, MD, from the University of Wuerzburg, lead investigator of the trial, is scheduled for 3:00 pm PDT on Thursday, October 12, 2023, in session III: Latest in Clinical Trials. "Considering the wide range of clinical manifestations of HPP, there's an unequivocal need to expand therapeutic opportunities for these patients," added Lothar Seefried, MD. "The encouraging early results confirming dose-dependent reductions of PLP and PPi levels upon treatment with ilofotase alfa underline the compound's therapeutic potential in that indication and I'm looking forward to evaluating ilofotase alfa in next stage clinical studies." About ilofotase alfa Ilofotase alfa is a proprietary recombinant alkaline phosphatase, constructed from two human isoforms of alkaline phosphatase, that has been shown to be stable and highly active in multiple clinical trials. The recombinant enzyme displays exquisite activity towards dephosphorylating and detoxifying damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS), ATP, ADP and other extracellular substrates that drive acute inflammation, coagulation and microvascular ischemia found in kidney following sepsis or ischemia-induced damage. Research has shown that ATP dephosphorylation has a double effect in protecting against kidney injury. When the pro-inflammatory ATP is dephosphorylated, the resulting adenosine further reduces inflammation through the activation of the immunosuppressive adenosine A2a receptor pathway. In hypophosphatasia, ilofotase alfa addresses elevated levels of pyridoxal-5′-phosphate (PLP), inorganic pyrophosphates (PPi), two disease related biomarkers that are related to, for example, bone mineralization and pain sensation. About hypophosphatasia HPP is a rare inherited disease characterized by a deficiency in alkaline phosphatase which is essential for bone mineralization and general functions. HPP patients of all ages can exhibit a wide variety of symptoms that worsen overtime, including bone injury, severe muscle pain and weakness. The disease can also lead to life-threatening complications in infants. The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) granted AM-Pharma Orphan Drug Designation (ODD) for ilofotase alfa in HPP. In preclinical models, ilofotase alfa was able to achieve improved overall survival of severe disease, as well as restoration of phenotypes associated with HPP. About AM-Pharma AM-Pharma strives to develop medicines for patients confronted with severe medical conditions. Our proprietary asset, ilofotase alfa, is being developed for the treatment of patients with acute kidney injury and has been granted FDA fast-track status. We also develop ilofotase alfa in the severe rare disease hypophosphatasia where ilofotase alfa has orphan drug status in the US and EU. With approximately 1,000 subjects evaluated to date in clinical trials, ilofotase alfa has a proven safety pro a demonstrated kidney benefit. We are a dedicated team driven to bring treatment options to severely ill patients, their families and acute care professionals. Find out more about us online at: . 1 Tournis, S., Yavropoulou, M. P., Polyzos, S. A., & Doulgeraki, A. (2021). Hypophosphatasia. Journal of Clinical Medicine, 10(23), 5676. View source version on businesswire.com: Contacts Investors: Juliane Bernholz, Chief Executive Officer j.bernholz@am-pharma.com Media: Trophic Communications Eva Mulder or Priscillia Perrin +31 6 52 33 15 79 am-pharma@trophic.eu Source: AM-Pharma View this news release online at: