Tebotelimab

Bispecific antibodies (commonly abbreviated as BsAbs) are an innovative class of biological drugs capable of simultaneously binding to two different antigens or epitopes. They exhibit unique therapeutic potential, offering higher specificity, possibly enhanced efficacy, and potentially reduced side effects compared to traditional monoclonal antibodies. 2023: A Breakthrough Year for Bispecific AntibodiesThe year 2023 marks a significant turning point for bispecific antibody products, with many entering the market in bulk. Major multinational companies like Roche and Johnson & Johnson are reaping the rewards of their investments in this field. Roche has seen notable success in the Chinese market, with the approval of its CD20/CD3 bispecific antibody Glofitamab and the ophthalmic bispecific antibody Faricimab. Johnson & Johnson's EGFR/c-MET bispecific antibody Amivantamab has shown great potential in treating EGFR-mutant non-small cell lung cancer (NSCLC) and has filed multiple marketing applications domestically. Bispecific antibodies are showing immense potential in the treatment of both hematologic malignancies and solid tumors, as well as opening new avenues in ophthalmology, driving market growth continuously. As domestic bispecific antibodies enter a period of substantial returns in the coming years, the market is expected to see significant growth. Domestic Progress: Akeso Biopharma and Others In 2023, Akeso Biopharma achieved annual profitability through its bispecific products. The PD-1/VEGF bispecific antibody Ivonevib (Credit: Akeso) received an upfront payment of $500 million, while Cadonilimab, as the first domestically produced bispecific antibody, reached sales of 1.358 billion RMB. In contrast, sales of the PD-1 antibody Penpulimab fell by 56% year-over-year to 273 million RMB, reflecting a directional shift in the antibody drug market. Bispecific antibodies have a broad development and application prospect, not only playing a crucial role in oncology but also showing potential in ophthalmology and hematological diseases. With technological advancements and market expansion, the "golden era" of bispecific antibodies has arrived. “Bispecific Antibodies” Ready to Take OffIn a review published in Nature, Raymond J. Deshaies, a member of the National Academy of Sciences, suggests that multispecific drugs, including bispecific antibodies, are poised to lead the "fourth pharmaceutical revolution." Expanding Horizons: Clinical Trials and Approvals On May 31: Akeso announced milestone clinical trial results: their self-developed Ivonescimab (PD-1/VEGF bispecific antibody) achieved the primary endpoint of progression-free survival (PFS) in a Phase III registration trial comparing it head-to-head with Pembrolizumab (Keytruda) as first-line treatment for PD-L1 positive locally advanced or metastatic NSCLC. The drug also marked the first globally to prove superior efficacy over Pembrolizumab in a Phase III monotherapy head-to-head clinical trial. Their PD-1/CTLA-4 bispecific antibody was also approved, achieving sales of 1.358 billion RMB in 2023. July 25: China's National Medical Products Administration (NMPA) Drug Evaluation Center (CDE) website announced that AbbVie's clinical trial application for ABBV-706, a lyophilized powder injection targeting SEZ6 ADC, was accepted. ABBV-706 is currently in Phase I clinical trials globally. August 9: Merck and curon announced a final agreement for Merck to acquire the bispecific antibody CN201 for $700 million upfront, aiming to treat B-cell-related diseases. August 21: Johnson & Johnson announced FDA approval of its EGFR/MET bispecific antibody Amivantamab in combination with the third-generation EGFR-TKI Lazcluze for first-line treatment of NSCLC with EGFR exon 19 deletions or exon 21 L858R substitutions. Clinical trials showed that this combination reduced the risk of disease progression or death by 30% compared to control drugs. August 26: Regeneron Pharmaceuticals announced the approval of its bispecific antibody Odronextamab in the EU. It became the first bispecific antibody to treat relapsed or refractory DLBCL and FL in patients who have undergone at least two systemic treatments. Odronextamab offers treatment convenience in outpatient settings and aims to achieve complete remission, improving patient treatment outcomes and quality of life. August 27: Navigator Medicines announced the completion of a $100 million Series A financing round. The funds will be used to promote its flagship product, NAV-240 (formerly known as IMB101), as well as other monoclonal and bispecific antibodies targeting OX40L. NAV-240 is a potential best-in-class bispecific antibody currently in Phase I clinical trials. It targets both OX40L and TNFα, two key players in the pathogenesis of various inflammatory diseases. The combined action on these two targets may enhance therapeutic efficacy, offering new treatment options for complex autoimmune diseases. RA Capital Management and Forbion co-led this round of financing, which will expedite the clinical research process of NAV-240. A multi-dose Phase Ib trial is expected to commence in the second half of this year. Additionally, IMBiologics will receive a $20 million upfront payment and is eligible for up to $925 million in development and commercial milestone payments. Domestic Innovative Bispecific Antibodies Show Promising Advances  At the 2024 ASCO Annual Meeting, several domestic enterprises showcased innovative bispecific antibody products and their clinical data. Innovent Biologics disclosed data on its innovative dual antibodies, IBI389 and IBI363. IBI389 is a bispecific antibody targeting CLDN18.2/CD3 and has completed the first patient dosing in the Phase I clinical trial for advanced malignancies. Preclinical results show that IBI389 can bind to tumor cells, even in cell lines with low CLDN18.2 expression, demonstrating significant antitumor effects. IBI363 is a PD-1/IL-2 bispecific antibody that has shown preliminary efficacy and safety in patients with melanoma and colorectal cancer. Sino Biopharm  unveiled data on its CD137/PD-L1 bispecific antibody FS222 in melanoma. Studies indicate that FS222 exhibits excellent antitumor activity in various tumor types, particularly in melanoma patients who have previously received PD-1 antibody treatment. The overall response rate reached 47.4%, and the disease control rate was 68.4%. These data suggest that domestic innovative products have made significant advances in the field of bispecific antibodies, potentially becoming a key area for international licensing in the future. Bispecific Antibody Drug Market to Surpass $10 Billion by 2024In the first half of 2024, the global bispecific antibody (BsAb) drug market witnessed significant growth, reaching $6 billion. The primary driver of this growth was Roche's VEGF/Ang2 BsAb, which alone achieved $2.154 billion in sales during this period. Although BsAbs are primarily used for cancer treatment, Roche's non-oncological BsAbs— specifically the FIX/FX BsAb for hemophilia and the VEGF/Ang2 BsAb for ophthalmic diseases—collectively generated $4.8 billion in sales, accounting for 80% of the entire BsAb market. According to Market.us data, the global BsAb drug market was valued at $5.73 billion in 2022 and $8 billion in 2023. It is projected to grow at a compound annual growth rate (CAGR) of 37.5% from 2024 to 2033, reaching approximately $192.6 billion by 2033. As of the end of 2023, the global BsAb drug market continued its growth trajectory, with CD3-targeting BsAbs comprising more than two-thirds of the approved BsAb drugs. This underscores the extensive application and importance of the CD3 target in the BsAb field. These CD3 BsAb drugs exhibit potent synergistic anti-tumor effects by simultaneously targeting tumor cells and immune cells, achieving significant clinical outcomes, particularly in the treatment of hematologic malignancies and certain solid tumors. Currently, 15 BsAb drugs have been approved globally, with two products from Akeso Bio standing out, marking a significant presence of Chinese innovative pharmaceutical companies in the global BsAb arena. With advancements in technology and innovation, the BsAb field has attracted substantial investments, covering areas such as tumor immunotherapy BsAbs, CD3 BsAbs, autoimmune target-combination BsAbs, breakthroughs in CD3 BsAbs for solid tumors, and BsAb ADCs. Looking ahead, BsAb drugs, due to their diverse mechanisms and differentiated designs, hold promise for achieving more clinical breakthroughs and becoming the next generation of biologic therapies for cancer, autoimmune, and infectious diseases. With the continuous expansion of the BsAb drug market and the maturation of R&D technologies, this field is expected to embrace further development opportunities and clinical application prospects. Multidisciplinary Progress of "Bispecific Antibodies"Bispecific antibodies (BsAbs) have experienced a significant surge in various medical fields, mainly concentrating on the following aspects: 1. Cancer Treatment BsAbs have demonstrated immense application potential and therapeutic effects in cancer treatment. For example, Akeso's Ivonescimab (PD-1/VEGF BsAb) showcased superior efficacy compared to Keytruda in a Phase III clinical trial for PD-L1 positive locally advanced or metastatic non-small cell lung cancer (NSCLC). Additionally, there are no longer any fundamental technical barriers to BsAb development, and numerous pharmaceutical companies are actively advancing research to discover new, remarkable bispecific structures. 2. Treatment of Autoimmune Diseases BsAbs also exhibit significant therapeutic potential in the field of autoimmune diseases. They can simultaneously target two different antigens or two different epitopes of the same antigen, thereby enhancing therapeutic efficacy through combined, multi-mechanistic pathways. 3. Treatment of Ophthalmic Diseases Roche's VEGF/Ang2 BsAb has made groundbreaking progress in the treatment of ophthalmic diseases, achieving sales of $2.154 billion. This highlights the commercial value and application potential of BsAbs in ophthalmic treatments. 4. Treatment of Hemophilia Hemlibra, an emicizumab-based BsAb, offers a new treatment option for patients with hemophilia A by bridging FIXa and FX, thereby promoting thrombin generation and restoring the coagulation process in patients. 5. Treatment of Non-Small Cell Lung Cancer (NSCLC) Johnson & Johnson's Rybrevant (EGFR/c-MET BsAb) has shown breakthrough efficacy in treating patients with metastatic NSCLC harboring EGFR exon 20 insertion mutations, becoming the first FDA-approved drug targeting this specific mutation. 6. BsAb-Antibody Drug Conjugates (ADCs) BsAb-ADCs, as an emerging strategy for cancer treatment, combine the advantages of BsAbs and ADCs, offering higher tumor selectivity and therapeutic efficacy. They have become a major focus of current research and development. In summary, BsAbs exhibit significant therapeutic potential and market value in cancer, autoimmune diseases, ophthalmic diseases, hemophilia, and NSCLC. They have become a new hotspot in pharmaceutical research and development. With continuous technological advancements and the launch of more BsAb drugs, more clinical breakthroughs and market growth are anticipated in the coming years. Future ProspectsLooking to the future, bispecific antibodies are emerging as stars in the medical field, demonstrating robust growth potential. Firstly, bispecific antibodies, by simultaneously targeting two different signaling pathways or antigens, significantly enhance therapeutic efficacy. This is particularly evident in the field of oncology, where PD-1/PD-L1 bispecific strategies not only relieve immune suppression on T cells but also effectively inhibit tumor angiogenesis, providing patients with more pronounced clinical benefits. Secondly, with ongoing technological advancements and industrial scaling, the production costs of bispecific antibodies are expected to gradually decrease. This reduction in cost will make these highly effective therapeutic drugs more affordable for a broader range of patients, thereby greatly improving drug accessibility. Furthermore, the application domains of bispecific antibodies are rapidly expanding. Beyond cancer treatment, their therapeutic potential is being explored in autoimmune diseases, ophthalmic diseases, hemophilia, and more, suggesting that they will exhibit unique therapeutic effects in an increasing number of disease areas. In addition, innovations and advancements in bispecific technology, such as the combination of bispecific antibodies with antibody-drug conjugates (ADCs), not only enhance the breadth and efficacy of treatment but also reduce the risk of drug resistance and activate different anti-tumor mechanisms. This provides more possibilities for clinical treatments. As the commercialization of bispecific antibody projects accelerates, it is expected that more bispecific drugs will be approved for market entry in the future, with the market size projected to grow continuously, potentially reaching approximately $192.6 billion by 2033. This presents substantial market opportunities for pharmaceutical companies and offers patients a wider array of treatment options. However, alongside the development of bispecific antibodies, ethical and social issues such as drug pricing and accessibility cannot be overlooked. It is essential to balance commercial interests and social responsibility during new drug research and development to ensure that every patient can benefit from the advancements in medical technology. In summary, the future development of bispecific antibodies is full of potential. With continuous technological breakthroughs and in-depth clinical research, we have reason to remain confident in the progress of bispecific technology and the hope it brings to patients, anticipating that it will contribute more benefits to human health. How to obtain the latest research advancements in the field of biopharmaceuticals? 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ROCKVILLE, Md., Feb. 24, 2022 (GLOBE NEWSWIRE) -- MacroGenics, Inc. (NASDAQ: MGNX), a biopharmaceutical company focused on developing and commercializing innovative antibody-based therapeutics for the treatment of cancer, today provided an update on its recent corporate progress and reported financial results for the year ended December 31, 2021. “We are excited about our 2022 plans for our B7-H3-directed programs for the potential treatment of multiple solid tumors. We believe we are well-positioned to be a leader in this promising field and are prioritizing our efforts around B7-H3. First, I am pleased to share that later this quarter, we plan to meet with the U.S. Food and Drug Administration (FDA) to discuss the design of a potential registration-directed study of MGC018 in patients with metastatic castration-resistant prostate cancer (mCRPC). Second, we expect to initiate a study of MGC018 in combination with lorigerlimab, our bispecific DART molecule targeting PD-1 and CTLA-4, in the coming weeks. And third, during the second half of this year, we intend to provide an update from a study of our second B7-H3 targeted molecule, enoblituzumab, being evaluated in combination with two of our checkpoint molecules in front-line squamous cell carcinoma of the head and neck (SCCHN). Beyond these B7-H3 programs, we are advancing several of our other clinical-stage molecules and have a variety of ongoing preclinical activities intended to expand our pipeline of differentiated investigational product candidates for the potential treatment of cancer,” said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. Updates on Proprietary Programs B7-H3 Programs: MacroGenics is developing two investigational, clinical product candidates that target B7-H3, an antigen with broad expression across multiple solid tumor types and a member of the B7 family of molecules involved in immune regulation. Recent highlights for these two molecules include: MGC018is an antibody-drug conjugate (ADC) that targets B7-H3. MacroGenics presented encouraging preliminary clinical results from an ongoing Phase 1/2 study of MGC018 in patients with solid tumors at the American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO) meetings in 2021. The Phase 1/2 study expansion cohorts are fully enrolled for patients with mCRPC (n=40) and smaller cohorts of patients (n=approximately 20 each) with non-small cell lung cancer (NSCLC), melanoma and triple negative breast cancer (TNBC), while the Company continues to recruit patients for the SCCHN cohort. MacroGenics plans to meet with FDA later this quarter to discuss its development strategy in mCRPC. In addition, the Company intends to provide an update on clinical data from the dose expansion cohorts in the second half of 2022 as the data further mature. Finally, beyond monotherapy, the Company expects to initiate a combination study of MGC018 with lorigerlimab across multiple indications in the coming weeks. Enoblituzumab is an Fc‐engineered, monoclonal antibody (mAb) that targets B7‐H3. MacroGenics continues to recruit patients into its Phase 2 study of enoblituzumab in combination with retifanlimab, the Company's investigational, anti-PD-1 antibody that was licensed to Incyte, in front-line patients with SCCHN who are PD-L1 positive and with tebotelimab in SCCHN patients who are PD-L1 negative. The Company expects to complete enrollment of the PD-L1 positive patient cohort during the first half of this year and provide an update on this cohort during the second half of the year. I-Mab, MacroGenics’ partner in Greater China, announced in December that the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) approved its Investigational New Drug (IND) submission for the initiation of a Phase 2 trial in China for enoblituzumab in combination with pembrolizumab in patients with solid tumors, including NSCLC, urothelial carcinoma and other selected cancers. DART Molecules for Immune Checkpoint Blockade: MacroGenics is studying multiple investigational, PD-1-directed programs to provide further differentiation from existing PD-1-based treatment options and enable combination opportunities across the Company’s portfolio. Recent highlights include: Lorigerlimab (formerly MGD019)is a bispecific, tetravalent DART molecule targeting PD-1 and CTLA-4. MacroGenics is conducting a Phase 1/2 dose expansion study in cohorts of patients with microsatellite stable colorectal cancer (MSS CRC), mCRPC, melanoma and checkpoint-naïve NSCLC. The Company anticipates sharing data from this ongoing study in the second half of 2022. As described above, MacroGenics expects to initiate a dose escalation study of MGC018 in combination with lorigerlimab in the coming weeks. Tebotelimab is a bispecific, tetravalent DART molecule targeting PD-1 and LAG-3. Tebotelimab was evaluated in a Phase 1/2 dose expansion study in several tumor types and is currently being studied in combination with enoblituzumab in SCCHN. The Company expects to provide an update on potential future development plans for tebotelimab in the second half of 2022. MacroGenics' partner in Greater China, Zai Lab, recently informed the Company that it has decided to discontinue development of tebotelimab for indications it was enrolling in its territory and is evaluating future development plans in other indications. Bispecific CD123 × CD3 DART molecule: MacroGenics has prioritized the development of MGD024, its investigational, next-generation CD123 × CD3 DART molecule, and will discontinue the development of flotetuzumab. Recent updates of these DART molecules include: MGD024is a next-generation, humanized CD123 × CD3 DART molecule designed to minimize cytokine-release syndrome, while maintaining anti-tumor cytolytic activity, and permitting intermittent dosing through a longer half-life. In November, MacroGenics announced submission of an IND application for MGD024 to FDA. At the American Society of Hematology (ASH) Annual Meeting in December, MacroGenics presented preclinical data from the combination of MGD024 with standard-of-care agents used to treat CD123-positive hematological malignancies. The Company expects to initiate a Phase 1 dose escalation study of MGD024 in patients with CD123-positive neoplasms, including acute myeloid leukemia (AML), pending IND clearance by FDA. Flotetuzumab is the Company’s first-generation, investigational, bispecific CD123 × CD3 DART molecule. An interim efficacy threshold from the single-arm study evaluating flotetuzumab in patients who were refractory to induction therapy was met with manageable safety. However, the Company has recently decided to prioritize the development of MGD024 and discontinue development of flotetuzumab, in view of the Company’s belief that MGD024 may offer certain advantages over flotetuzumab, including easier dose administration and a more facile means to combine with other agents. Margetuximab is an Fc-engineered mAb that targets the HER2 oncoprotein, which is expressed by certain breast, gastroesophageal and other solid tumor cells. MARGENZA® (margetuximab-cmkb) was launched in March 2021 by MacroGenics and its commercial partner, Eversana Life Science Services, LLC, for the treatment of adult patients with metastatic HER2-positive breast cancer, in combination with chemotherapy, who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease. In January 2022, Zai Lab announced that the China NMPA accepted the New Drug Application (NDA) for margetuximab for the treatment of the same HER2-positive breast cancer indication. Zai Lab recently informed MacroGenics that they have decided to discontinue enrollment of Module B of the MAHOGANY study in gastric cancer based on their review of both the clinical data and the changing treatment landscape. MacroGenics previously announced in November 2021 that the Company had decided to discontinue enrollment of Module A of the MAHOGANY study. Selected Partnered Program Updates: IMGC936is an investigational ADC that targets ADAM9, a cell surface protein over-expressed in several solid tumor types, and is being developed jointly under a 50/50 collaboration with ImmunoGen, Inc. Under the collaboration, ImmunoGen is leading clinical development of IMGC936 in a Phase 1 clinical trial evaluating safety and pharmacokinetics in multiple solid tumors and has indicated they anticipate disclosing initial data in 2022. Teplizumab is an investigational, anti-CD3 monoclonal antibody acquired from MacroGenics by Provention Bio, Inc. under an asset purchase agreement in 2018 for which MacroGenics is entitled to receive future milestone payments and royalties on net sales. Provention is developing teplizumab for the treatment of type 1 diabetes (T1D). On February 22, 2022, Provention announced that it had resubmitted the Biologics License Application (BLA) for teplizumab for the delay of clinical T1D in at-risk individuals. The BLA resubmission followed Provention’s Type B meeting with FDA earlier in the year. 2021 Financial Results Cash Position: Cash, cash equivalents and marketable securities as of December 31, 2021, were $243.6 million, compared to $272.5 million as of December 31, 2020. Revenue: Total revenue, consisting primarily of revenue from collaborative agreements, was $77.4 million for the year ended December 31, 2021, compared to total revenue of $104.9 million for the year ended December 31, 2020. Revenue for the year ended December 31, 2021 included $12.3 million net sales of MARGENZA. R&D Expenses: Research and development expenses were $214.6 million for the year ended December 31, 2021, compared to $193.2 million for the year ended December 31, 2020. The increase was primarily related to development, manufacturing and clinical trial costs related to MGC018, as well as other preclinical molecules and increased clinical expenses related to enoblituzumab and lorigerlimab. These increases were partially offset by decreased development and manufacturing costs related to retifanlimab for Incyte and decreased clinical costs and BLA support for margetuximab. SG&A Expenses: Selling, general and administrative expenses were $63.0 million for the year ended December 31, 2021, compared to $42.7 million for the year ended December 31, 2020. The increase was primarily related to the MARGENZA launch, as well as labor-related costs and legal expenses. Net Loss: Net loss was $202.1 million for the year ended December 31, 2021, compared to net loss of $129.7 million for the year ended December 31, 2020. Shares Outstanding: Shares outstanding as of December 31, 2021 were 61,307,428.Cash Runway Guidance: MacroGenics anticipates that its cash, cash equivalents and marketable securities as of December 31, 2021, plus anticipated and potential collaboration payments, and product revenues should enable it to fund its operations through 2023. Such guidance does not reflect anticipated expenditures related to the potential late-stage development of MGC018 in mCRPC or further expansion of studies currently ongoing. Conference Call Information MacroGenics will host a conference call today at 4:30 p.m. (ET) to discuss financial results for the year ended December 31, 2021 and provide a corporate update. To participate in the conference call, please dial (877) 303-6253 (domestic) or (973) 409-9610 (international) five minutes prior to the start of the call and provide the Conference ID: 1067087. The listen-only webcast of the conference call can be accessed under "Events & Presentations" in the Investor Relations section of the Company's website at http://ir.macrogenics.com/events.cfm. A replay of the webcast will be available shortly after the conclusion of the call and archived on the Company's website for 30 days following the call. MACROGENICS, INC.SELECTED CONSOLIDATED BALANCE SHEET DATA(Amounts in thousands) December 31, 2021 December 31, 2020 Cash, cash equivalents and marketable securities $ 243,616 $ 272,531 Total assets 335,245 378,743 Deferred revenue 20,646 11,382 Total stockholders' equity 239,618 295,884 MACROGENICS, INC.CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS(Unaudited) (Amounts in thousands, except share and per share data) Year Ended December 31, 2021 2020 2019 Revenues: Revenue from collaborative and other agreements $ 63,294 $ 97,764 $ 62,024 Product revenue, net 12,349 — — Revenue from government agreements 1,804 7,119 2,164 Total revenues 77,447 104,883 64,188 Costs and expenses: Cost of product sales 2,651 — — Research and development 214,577 193,201 195,309 Selling, general and administrative 63,014 42,742 46,064 Total costs and expenses 280,242 235,943 241,373 Loss from operations (202,795 ) (131,060 ) (177,185 ) Other income 680 1,321 25,374 Net loss (202,115 ) (129,739 ) (151,811 ) Other comprehensive income: Unrealized gain (loss) on investments (54 ) (23 ) 19 Comprehensive loss $ (202,169 ) $ (129,762 ) $ (151,792 ) Basic and diluted net loss per common share $ (3.37 ) $ (2.47 ) $ (3.16 ) Basic and diluted weighted average common shares outstanding 59,944,717 52,442,389 48,082,728 About MacroGenics, Inc. MacroGenics (the Company) is a biopharmaceutical company focused on developing and commercializing innovative monoclonal antibody-based therapeutics for the treatment of cancer. The Company generates its pipeline of product candidates primarily from its proprietary suite of next-generation antibody-based technology platforms, which have applicability across broad therapeutic domains. The combination of MacroGenics' technology platforms and protein engineering expertise has allowed the Company to generate promising product candidates and enter into several strategic collaborations with global pharmaceutical and biotechnology companies. For more information, please see the Company's website at www.macrogenics.com. MacroGenics, the MacroGenics logo, MARGENZA and DART are trademarks or registered trademarks of MacroGenics, Inc.