BNT-211

Announced positive data from multiple mRNA cancer vaccine clinical trials, including topline results from the ongoing Phase 2 evaluating FixVac candidate BNT111Launched updated variant-adapted COVID-19 vaccine in the European Union (“EU”), received approval in the United Kingdom and initiated rolling supplemental Biologics Licensing Application (“sBLA”) with the United States Food and Drug Administration (“U.S. FDA”)Reiterates guidance for total revenues in the range of €2.5-3.1 billionReports second quarter 2024 revenues of €128.7 million, net loss of €807.8 million and loss per share of €3.36 ($3.621)Invested €525.6 million or approximately 90% of the Company’s total R&D spend in Q2 in non-COVID-19 related activities, mainly oncology and mRNA; investments are in line with the reiterated full-year R&D expense guidanceEnded the second quarter of 2024 with €18.5 billion in cash, cash equivalents and security investments Conference call and webcast scheduled for August 5, 2024, at 8:00 a.m. EDT (2:00 p.m. CEST) MAINZ, Germany, August 5, 2024 (GLOBE NEWSWIRE) -- BioNTech SE (Nasdaq: BNTX, “BioNTech” or “the Company”) today reported financial results for the three and six months ended June 30, 2024, and provided an update on its corporate progress. “The year to date has been marked by significant data updates across our oncology portfolio. These readouts reinforce the potential of our platform technologies including our individualized and off-the-shelf mRNA vaccine platforms, iNeST and FixVac. We have also advanced our strategy by initiating clinical trials evaluating novel combinations of synergistic drug candidates. Notably, we dosed the first patient in a trial evaluating the combination of the TROP2 antibody-drug conjugate BNT325/DB-1305 and the PD-L1-VEGF-A bispecific BNT327/PM8002, aiming to harness the potent anti-tumor activity of antibody drug conjugates along with the sustained benefit of immunomodulators,” said Prof. Ugur Sahin, M.D., CEO and Co-Founder of BioNTech. “In addition, we have started commercializing variant-adapted COVID-19 vaccines for the upcoming season, while accelerating our clinical development efforts to realize the full potential of our technologies. We are making progress towards our goal of becoming a company with marketed medicines for cancer and infectious diseases.” Financial Review for Second Quarter and First Half of 2024 in millions €, except per share data Second Quarter 2024 Second Quarter 2023 First Half 2024 First Half 2023Revenues 128.7 167.7 316.3 1,444.7Net Profit / (Loss) (807.8) (190.4) (1,122.9) 311.8(Loss) / Diluted Earnings per Share (3.36) (0.79) (4.67) 1.28 Revenues reported were €128.7 million for the three months ended June 30, 2024, compared to €167.7 million for the comparative prior year period. For the six months ended June 30, 2024, revenues were €316.3 million, compared to €1,444.7 million for the comparative prior year period. The year-over-year change was mainly due to lower revenues from the sales of the Company’s COVID-19 vaccines worldwide resulting from the continued shift in demand from a pandemic to a seasonal endemic COVID-19 vaccine market. Cost of sales were €59.8 million for the three months ended June 30, 2024, compared to €162.9 million for the comparative prior year period. For the six months ended June 30, 2024, cost of sales were €118.9 million, compared to €258.9 million for the comparative prior year period. The change was mainly due to COVID-19 vaccine production in line with demand. Research and development (“R&D”) expenses were €584.6 million for the three months ended June 30, 2024, compared to €373.4 million for the comparative prior year period. For the six months ended June 30, 2024, R&D expenses were €1,092.1 million, compared to €707.4 million for the comparative prior year period. R&D expenses were mainly influenced by progressing clinical studies for the Company’s late-stage oncology pipeline candidates. Further contributions to the increase came from wages, benefits and social security expenses resulting from an increase in headcount. Sales, general and administrative (“SG&A”) expenses2, in total, amounted to €183.8 million for the three months ended June 30, 2024, compared to €137.9 million for the comparative prior year period. For the six months ended June 30, 2024, SG&A expenses were €316.4 million, compared to €261.9 million for the comparative prior year period. SG&A expenses were primarily driven by increased expenses for IT environment and wages, benefits, and social security expenses resulting from an increase in headcount. Other operating result amounted to €266.7 million negative operating result during the three months ended June 30, 2024, compared to €56.8 million negative operating result for the comparative prior year period. For the six months ended June 30, 2023, other operating result amounted to €262.3 million negative operating result compared with €125.4 million negative operating result for the prior year period. This change was primarily due to the recording of a provision related to a contractual dispute. Income taxes were accrued with an amount of €2.0 million of tax expenses for the three months ended June 30, 2024, compared to €221.8 million of realized tax income for the comparative prior year period. For the six months ended June 30, 2024, income taxes were realized with an amount of €14.7 million of tax income for the six months ended June 30, 2024, compared to €16.3 million of realized tax income for the comparative prior year period. The effective income tax rate for the six months ended June 30, 2024, was approximately 1.3%. Net loss was €807.8 million for the three months ended June 30, 2024, compared to €190.4 million loss for the comparative prior year period. For the six months ended June 30, 2024, loss was €1,122.9 million for the six months ended June 30, 2024, compared to a profit of €311.8 million for the comparative prior year period. Cash and cash equivalents plus security investments as of June 30, 2024, reached €18,485.1 million, comprising €10,376.7 million cash and cash equivalents, €6,916.7 million current security investments and €1,191.7 million non-current security investments. This position increased during the second quarter of 2024 largely attributable to a cash payment received from BioNTech’s collaboration partner Pfizer Inc. (“Pfizer”). Loss per share was €3.36 for the three months ended June 30, 2024, compared to €0.79 for the comparative prior year period. For the six months ended June 30, 2024, loss per share was €4.67, compared to diluted earnings per share of €1.28 for the comparative prior year period. Shares outstanding as of June 30, 2024 were 237,766,235, excluding 10,785,965 shares held in treasury. “Our second quarter revenues correspond to the current demand of a seasonal endemic COVID-19 vaccine market,” said Jens Holstein, CFO of BioNTech. “Supported by our strong financial position, we will continue to focus on our long-term growth strategy throughout the remainder of the year. This includes our clinical pipeline for individualized therapies, the build-out of our manufacturing capacities and capabilities to support additional late-stage trials as well as our commercialization activities. These investments build the foundation for the next stage of growth and the transformation of BioNTech into a multi-product company.” 2024 Financial Year Guidance3 Reiterated The Company reiterates its prior outlook for the financial year: Total revenues for the 2024 financial year €2.5 billion - €3.1 billion BioNTech expects revenues for the full 2024 financial year to be in the range of €2.5 to €3.1 billion. The range reflects certain assumptions and expectations, including, but not limited to: the timing and granting of regulatory approvals and recommendations; COVID-19 vaccine uptake and price levels; inventory write-downs by BioNTech’s collaboration partner Pfizer that would negatively influence BioNTech’s revenues; seasonal variations in SARS-CoV-2 circulation and vaccination uptake, which are expected to lead to demand peaks in the autumn and winter compared to other seasons; and revenues from a pandemic preparedness contract with the German government as well as revenues from the BioNTech Group service businesses, namely InstaDeep Ltd., JPT Peptide Technologies GmbH, and in Idar-Oberstein at BioNTech Innovative Manufacturing Services GmbH. Generally, the Company continues to remain largely dependent on revenues generated in its collaboration partner’s territories in 2024. Planned 2024 Financial Year Expenses and Capex: R&D expenses4 €2.4 billion - €2.6 billion SG&A expenses €700 million - €800 million Capital expenditures for operating activities €400 million - €500 million The full interim unaudited condensed consolidated financial statements can be found in BioNTech’s Report on Form 6-K for the period ended June 30, 2024, filed today with the United States Securities and Exchange Commission (“SEC”) and available at https://www.sec.gov/. Endnotes 1 Calculated applying the average foreign exchange rate for the six months ended June 30, 2024, as published by the German Central Bank (Deutsche Bundesbank). 2 “SG&A expenses’’ includes sales and marketing expenses as well as general and administrative expenses. 3 Guidance excludes external risks that are not yet known and/or quantifiable. It does not include potential payments resulting from the outcomes of ongoing and/or future legal disputes or related activity, such as judgements or settlements, which may have a material effect on the Company’s results of operations and/or cash flows. BioNTech continues to expect to report a loss for the 2024 financial year and expects to recognize the vast majority of its full year revenues mostly in the fourth quarter. 4 Numbers include effects identified from additional collaborations or potential M&A transactions to the extent disclosed and are subject to update due to future developments. Operational Review of the Second Quarter 2024, Key Post Period-End Events and Outlook Variant-adapted Monovalent COVID-19 Vaccines (COMIRNATY®) In April 2024, the World Health Organization (“WHO”), the European Medicines Agency (“EMA”) and, subsequently, other health authorities, provided guidance highlighting that updated vaccines targeting Omicron JN.1 or JN.1 sublineages may contribute to maintaining protection against COVID-19 during the upcoming fall and winter seasons. On June 27, 2024, BioNTech and Pfizer announced that the Committee for Medicinal Products for Human Use (“CHMP”) of the EMA recommended marketing authorization for the companies’ Omicron JN.1-adapted monovalent COVID-19 vaccine (COMIRNATY® JN.1) for active immunization to prevent COVID-19 caused by SARS-CoV-2 in individuals six months of age and older. On July 3, 2024, the European Commission (“EC”) adopted a decision following the CHMP’s recommendation. Shortly following the EC decision, the updated vaccine was made available to ship to EU member states.On June 6, 2024, the U.S. FDA’s Vaccines and Related Biological Products Advisory Committee (“VRBPAC”) issued guidance recommending the manufacturing of a JN.1-adapted monovalent COVID-19 vaccine for the 2024/2025 fall and winter seasons. On June 13, 2024, the U.S. FDA announced the KP.2 strain as the preferred JN.1-lineage for COVID-19 vaccines (2024-2025 Formula). In June 2024, BioNTech and Pfizer submitted regulatory applications to the U.S. FDA for the companies’ Omicron JN.1-adapted monovalent vaccine, and initiated a rolling sBLA for an Omicron KP.2-adapted monovalent vaccine. The companies plan to prepare shipments in the United States of KP.2-adapted monovalent COVID-19 vaccines for fast delivery following potential regulatory approval, currently expected in September 2024.On July 24, 2024, the United Kingdom’s Medicines and Healthcare products Regulatory Agency (“MHRA”) approved the companies’ Omicron JN.1-adapted vaccine. COVID-19 – Influenza Combination Vaccine Program BNT162b2 + BNT161 is an mRNA-based combination vaccine program against COVID-19 and influenza being developed in collaboration with Pfizer. Top-line data from the Phase 1/2 trial (NCT05596734) demonstrated robust immune responses to influenza A, influenza B, and SARS-CoV-2 strains and that the safety profile of the candidates was consistent with the profile of the companies’ COVID-19 vaccine. A Phase 3 clinical trial (NCT06178991) is fully enrolled and data are expected later this year. Select Oncology Pipeline Highlights Cancer Vaccine Programs BNT111 is based on BioNTech’s FixVac platform, and is a wholly owned, systemically administered, off-the-shelf uridine mRNA-lipoplex based cancer vaccine candidate encoding shared melanoma associated antigens. A randomized Phase 2 clinical trial (NCT04526899) being conducted in collaboration with Regeneron Pharmaceuticals Inc. (“Regeneron”) is ongoing to evaluate BNT111 in combination with cemiplimab, BNT111 alone, or cemiplimab alone in anti-PD-1-/anti-PD-L1 refractory/relapsed, unresectable stage III or IV melanoma.In July 2024, BioNTech announced that the study met its primary efficacy outcome measure, demonstrating a statistically significant improvement in overall response rate (“ORR”) in patients treated with BNT111 in combination with the anti-PD-1 checkpoint inhibitor, cemiplimab, as compared to a historical control in this indication and treatment setting. The ORR in the cemiplimab monotherapy arm was in line with the historical control of anti-PD-L1 or anti-CTLA-4 treatments in this patient group. The treatment was well tolerated and the safety profile of BNT111 in combination with cemiplimab in this trial was consistent with previous clinical trials assessing BNT111 in combination with anti-PD-L1-containing treatments. The Phase 2 trial will continue as planned to further assess the secondary endpoints which were not mature at the time of the primary analysis.BioNTech plans to present data from this trial at an upcoming medical conference. BNT113 is a cancer vaccine candidate based on FixVac’s platform encoding for shared antigens associated with Human Papilloma Virus (“HPV16+”) head and neck cancer. A global, randomized Phase 2 clinical trial (NCT04534205) evaluating BNT113 in combination with pembrolizumab versus pembrolizumab monotherapy as a first-line treatment in patients with unresectable recurrent or metastatic HPV16+ head and neck squamous cell carcinoma expressing PD-L1 is ongoing. Data updates are expected to be presented at the 2024 Congress of the European Society of Medical Oncology (“ESMO”) taking place from September 13-17, 2024 in Barcelona, Spain. Abstract Title: Exploratory efficacy and translational results from the safety run in of AHEAD-MERIT, a phase II trial of first line pembrolizumab plus the fixed-antigen cancer vaccine BNT113 in advanced HPV16+ HNSCC Poster Date: September 14, 2024Presentation Number: 877PAuthor: C. N. F. Saba Abstract Title: HARE-40: A phase I/II trial of therapeutic HPV vaccine (BNT113) in patients with HPV16 driven carcinomaMini-oral Date & Time: September 16, 2024, 11:15 - 11:20 a.m. CESTPresentation Number: 999MMOAuthor: C. Ottensmeier Autogene cevumeran (BNT122) is a uridine mRNA-lipoplex based cancer vaccine candidate for individualized neoantigen-specific immunotherapy (“iNeST”) being developed in collaboration with Genentech, Inc. (“Genentech”), a member of the Roche Group (“Roche”). Autogene cevumeran is being evaluated in ongoing Phase 2 trials in adjuvant resected pancreatic ductal adenocarcinoma (“PDAC”) (NCT05968326), first-line melanoma (NCT03815058) and adjuvant colorectal cancer (“CRC”) (NCT04486378). A Phase 2 clinical trial in an additional indication is planned.In June 2024, epidemiologic data were presented at the American Society of Clinical Oncology (“ASCO”) Annual Meeting, including data on post-operative circulating tumor DNA (“ctDNA”) prevalence and prognostic value in disease-free survival, from an observational study (NCT04813627) in patients with resected high-risk stage II/III CRC. These epidemiological and prognostic data are supportive of the ongoing interventional Phase 2 clinical trial (NCT04486378).Also in June 2024, at the 2024 European Society for Medical Oncology Gastrointestinal Cancers (“ESMO-GI”) Congress, immunogenicity data were presented from the biomarker cohort of the ongoing Phase 2 (NCT04486378) that enrolled patients irrespective of post-surgical ctDNA status. The data indicate that autogene cevumeran is highly immunogenic and induces de novo polyepitopic, ex vivo detectable T-cell responses in all evaluable patients with resected​ stage II (high risk) or III CRC after completion of adjuvant chemotherapy.​ Among patients included in the immunogenicity analysis, all (12/12) were disease-free at data cut off.Preliminary data from the ongoing Phase 2 clinical trial (NCT04486378) in stage II (high risk) and III ctDNA+ adjuvant CRC is expected in late 2025 or 2026. Next-Generation Immune Checkpoint Immunomodulator Programs BNT327/PM8002 is a bispecific antibody candidate combining PD-L1 checkpoint inhibition with VEGF-A neutralization and is being developed in collaboration with Biotheus Inc. (“Biotheus”). BNT327/PM8002 is currently being evaluated in multiple Phase 2 and Phase 3 clinical trials in China to assess the efficacy and safety of the candidate as monotherapy or in combination with chemotherapy in various indications.In June 2024, at the 2024 ASCO Annual Meeting, monotherapy data were presented from an ongoing Phase 1/2 clinical trial (NCT05918445) for cohorts of patients with advanced cervical cancer (“CC”), platinum-resistant recurrent ovarian cancer (“PROC”), and advanced non-small cell lung cancer (“NSCLC”). Data on 48 patients with advanced CC showed an ORR of 42.2% (52.4% in patients with PD-L1-positive tumors), a disease control rate (“DCR”) of 93.3%, and a median progression-free survival (“mPFS”) of 8.3 months. Data on 39 patients with PROC showed an ORR of 20.6%, a DCR of 67.7%, and a mPFS of 5.5 months. Treatment related adverse events (“TRAEs”) occurred in 95.4% of patients (83/87) with ≥ Grade 3 TRAEs in 36.8% (32/87) and 14.9% (13/87) of patients discontinued BNT327/PM8002 treatment due to TRAEs. Median follow-up time in patients with CC and PROC was 13.8 months and 14.8 months, respectively. Data on 61 patients with non-squamous NSCLC were also presented. Data on 17 evaluable patients with untreated NSCLC wild-type and PD-L1-positive showed an ORR of 47.1%, a DCR of 100% and a mPFS of 13.6 months at a median follow-up of 11.3 months. Data on 36 evaluable patients with epidermal growth factor receptor (“EGFR”)-mutant NSCLC after progression on prior EGFR-tyrosine kinase inhibitor treatment showed an ORR of 19.4%, a DCR of 69.4% and a mPFS of 5.5 months at a median follow-up of 12.6 months. Data from 8 evaluable patients with EGFR/anaplastic lymphoma kinase (“ALK”) wild-type NSCLC that progressed after anti-PD-1/L1 therapy and platinum-based chemotherapy showed an ORR of 12.5%, a DCR of 62.5%, and a mPFS of 5.8 months at a median follow-up of 5.8 months. TRAEs occurred in 85.2% of patients (52/61) with ≥Grade 3 TRAEs in 19.7% (12/61), serious adverse events were observed in 24.6% (15/61) of patients, 8.2% (5/61) of patients discontinued BNT327/PM8002 treatment due to TRAEs. In June 2024, the first patient was dosed in the Phase 1/2 clinical trial (NCT05438329) evaluating the combination of BNT327/PM8002 with BNT325/DB-1305, an antibody-drug conjugate (“ADC”) candidate targeting TROP-2. Additional trials with novel BNT327 and other ADC combinations are planned to begin this year.Two Phase 2 dose optimization studies are expected to start soon. A Phase 2 clinical trial (NCT06449222) to evaluate the safety, efficacy, and pharmacokinetics of BNT327/PM8002 at two dose levels in combination with chemotherapy in the first- and second-line treatment of patients with locally advanced/metastatic triple negative breast cancer (“TNBC”).A Phase 2 clinical trial (NCT06449209) to evaluate BNT327/PM8002 in combination with chemotherapy in patients with untreated extended-stage small-cell lung cancer (“ES-SCLC”) or small-cell lung cancer (“SCLC”) progressed on first- or second-line treatment.Data from these studies are expected as early as 2025. At the 2024 ESMO Congress the following datasets will be presented: Abstract Title: A Phase II Safety and Efficacy Study of PM8002/BNT-327 in Combination with Chemotherapy in Patients with EGFR-mutated NSCLCMini-oral Presentation Date & Time: September 14, 2024, 10:25 - 10:30 a.m. CESTPresentation Number: 1255MOAuthor: Y-L. Wu Abstract Title: A Phase Ib/II Study to Assess the Safety and Efficacy of PM8002/BNT327 in Combination with Nab-Paclitaxel for First Line Treatment of Locally Advanced or Metastatic Triple-Negative Breast CancerMini-oral Presentation Date & Time: September 16, 2024, 08:35 - 08:40 a.m. CESTPresentation Number: 348MOAuthor: J. Wu Abstract Title: A Phase Ib/IIa Trial to Evaluate the Safety and Efficacy of PM8002/ BNT327, a Bispecific Antibody Targeting PD-L1 and VEGF-A, as a Monotherapy in Patients with advanced renal cell carcinomaPoster Date: September 15, 2024Presentation Number: 1692PAuthor: X. Sheng BNT311/GEN1046 (acasunlimab) is a potential first-in-class bispecific antibody candidate combining PD-L1 checkpoint inhibition with 4-1BB costimulatory activation that is being developed for the treatment of solid tumors. A Phase 2, multi-center, randomized, open-label clinical trial (NCT05117242) of BNT311/GEN1046 (acasunlimab) as monotherapy and in combination with pembrolizumab is ongoing in patients with relapsed/refractory metastatic NSCLC and a tumor PD-L1 expression of tumor proportion score, or TPS, of ≥1% after treatment with standard of care therapy with an immune checkpoint inhibitor. The primary endpoint is ORR according to Response Evaluation Criteria in Solid Tumors, or RECIST v1.1. Secondary endpoints include duration of response (“DOR”), time to response (“TTR”), progression-free survival (“PFS”), overall survival “OS” and safety.Data from the ongoing Phase 2 trial (NCT05117242) evaluating BNT311/GEN1046 (acasunlimab) in combination with pembrolizumab in pretreated NSCLC patients were presented at the 2024 ASCO Annual Meeting. The results showed a 12-month OS rate of 69%, a median OS (“mOS”) of 17.5 months, and a 30% ORR (confirmed ORR 17%) at the time of data cut-off in patients treated with the combination of BNT311/GEN1046 (acasunlimab) and pembrolizumab every 6 weeks. Anti-tumor activity was observed in patients with tumor proportion score (“TPS”) of 1–49% and ≥50%, in patients with <6 months and ≥6 months of previous immune checkpoint inhibitor (“CPI”) treatment, and in patients with squamous and non-squamous histology. Adverse events were consistent with the safety profiles of the individual drugs and TRAEs were primarily Grade 1 and 2.Updated data from this ongoing trial is expected to be presented at the 2024 World Conference on Lung Cancer (“WCLC”) taking place from September 7-10, 2024 in San Diego, California, U.S. Abstract Title: Dosing Regimen for Acasunlimab (DuoBody-PD-L1x4-1BB) In Combination with Pembrolizumab Poster Presentation Date & Time: September 9, 2024, 18:30-20:00 PDT Presentation Number: 845Author: G. Bajaj Abstract Title: Acasunlimab Alone or in Combination with Pembrolizumab for Previously Treated Metastatic Non-Small Cell Lung CancerMini-oral Presentation Date & Time: September 10, 2024, 15:07 - 15:12 PDTPresentation Number: 1309Author: L. Paz-Ares While the emerging clinical profile of BNT311/GEN1046 (acasunlimab) is encouraging, for reasons relating to portfolio strategy, BioNTech opted not to participate in the further development of the program, including a planned Phase 3 trial. BioNTech and Genmab A/S (“Genmab”) will continue their collaboration under the existing agreements which was expanded in 2022. ADC Programs BNT323/DB-1303 is an ADC candidate targeting Human Epidermal Growth Factor 2 (“HER2”) that is being developed in collaboration with Duality Biologics (Suzhou) Co. Ltd. (“DualityBio”). BNT323/DB-1303 is being evaluated in a Phase 1/2 clinical trial (NCT05150691) in patients with advanced/unresectable, recurrent or metastatic HER2-expressing solid tumors. A potentially registrational cohort with HER2-expressing (IHC3+, 2+, 1+ or ISH-positive) patients with advanced/recurrent endometrial carcinoma has completed enrollment. Data from this cohort are expected in 2025.A confirmatory Phase 3 trial (NCT06340568) in patients with advanced endometrial cancer is planned to start in 2024.A pivotal Phase 3 trial (NCT06018337) evaluating BNT323/DB-1303 in patients with Hormone Receptor-positive (“HR+”) and HER2-low metastatic breast cancer (“BC”) that have progressed on hormone therapy and/or cyclin-dependent kinase 4/6 (“CDK4/6”) inhibition is ongoing.Topline data from the ongoing Phase 3 trial in HR+ and HER2-low metastatic BC that have progressed on hormone therapy and/or CDK4/6 inhibition are expected as early as 2025. BNT324/DB-1311 is an ADC candidate targeting B7H3 that is being developed in collaboration with DualityBio. A first-in-human, open-label Phase 1/2a clinical trial (NCT05914116) evaluating BNT324/DB-1311 in patients with advanced solid tumors is ongoing.In June 2024, BioNTech and DualityBio announced that BNT324/DB-1311 was granted Fast Track designation by the U.S. FDA for the treatment of patients with advanced/unresectable or metastatic castration-resistant prostate cancer who have progressed on or after standard systemic regimens.In July 2024, the U.S. FDA granted Orphan Drug designation to BNT324/DB-1311 for the treatment of patients with advanced or metastatic esophageal squamous cell carcinoma. BNT326/YL202 is an ADC candidate targeting HER3 that is being developed in collaboration with MediLink Therapeutics (Suzhou) Co., Ltd. (“MediLink”). A multicenter, international, open-label, first-in-human Phase 1 clinical trial (NCT05653752), sponsored by MediLink, evaluating BNT326/YL202 as a later-line treatment in patients with locally advanced or metastatic EGFR-mutated NSCLC or HR+ and HER2-negative BC is on partial clinical hold by the U.S. FDA, as announced on June 17, 2024. BioNTech and MediLink are working to address the U.S. FDA’s requirements and resolve the partial clinical hold.Preliminary data from this study were presented at the 2024 ASCO Annual Meeting. BNT326/YL202 demonstrated encouraging activity in heavily pretreated locally advanced/metastatic NSCLC and BC with an ORR of 42.3% (22 out of 52 evaluable patients) and a DCR of 94.2% (49/52), with responses seen from the first dose level at 0.5 mg/kg. The safety profile of BNT326/YL202 was consistent with its mechanism of action and dose-dependent. The most common TRAEs were due to hematologic toxicity and gastrointestinal disorders. 7.3% (4/55) of patients discontinued treatment due to TRAEs, and there were 3 treatment-related Grade 5 events (deaths) at higher doses. Further clinical development is expected to focus on dose levels below 4.0 mg/kg, where the safety profile was manageable and encouraging clinical activity was observed. Cell Therapy Programs BNT211 consists of two investigational medicinal products: a CAR-T cell product candidate targeting Claudin-6 (“CLDN6”)-positive solid tumors in combination with a CAR-T cell-amplifying RNA vaccine (“CARVac”) encoding CLDN6. A first-in-human, open-label, multi-center Phase 1 dose escalation and dose expansion basket trial (NCT04503278) evaluating CLDN6 CAR-T cells as monotherapy or in combination with CLDN6 CARVac in patients with CLDN6-positive relapsed or refractory solid tumors, including ovarian cancers and testicular germ cell tumors, is ongoing.A data update is expected to be presented at the 2024 ESMO Congress. Abstract Title: Updated results from BNT211-01 (NCT04503278), an ongoing, first-in-human, Phase 1 study evaluating safety and efficacy of CLDN6 CAR T cells and a CLDN6-encoding mRNA vaccine in patients with relapsed/refractory CLDN6+ solid tumorsMini-oral Presentation Date & Time: September 15, 2024, 15:45 - 15:55 CESTPresentation Number: 611OAuthor: J. B. Haanen A pivotal Phase 2 trial in patients with testicular germ cell tumors is expected to start in 2025 based on encouraging data in this patient group observed in the Phase 1 trial.BioNTech presented an analysis of real-world evidence investigating overall survival and treatment patterns of patients with testicular germ cell tumors receiving palliative chemotherapy at the 2024 ASCO Annual Meeting. This analysis will inform the design of the Company’s planned pivotal clinical trial to evaluate BNT211 in patients with germ cell tumors. Corporate Update for the Second Quarter 2024 and Key Post Period-End Events In May 2024, BioNTech expanded its strategic partnership with the Coalition for Epidemic Preparedness Innovations (“CEPI”) to contribute to building a sustainable and resilient end-to-end African vaccine ecosystem. CEPI is committing up to US $145 million to support BioNTech in broadening the scope of the manufacturing facility in Kigali, Rwanda. These capabilities will contribute to BioNTech and CEPI’s efforts to better prepare for potential future epidemic and pandemic threats in Africa.On July 1, 2024, Annemarie Hanekamp joined the Company’s Management Board as Chief Commercial Officer and James Ryan, Ph.D., Chief Legal Officer, also assumed the role of Chief Business Officer. Upcoming Investor and Analyst Events Innovation Series (AI Day): October 1, 2024Third Quarter 2024 Financial Results and Corporate Update: November 4, 2024Innovation Series: November 14, 2024 Conference Call and Webcast Information BioNTech invites investors and the general public to join a conference call and webcast with investment analysts today, August 5, 2024, at 8:00 a.m. EDT (2:00 p.m. CEST) to report its financial results and provide a corporate update for the second quarter of 2024. To access the live conference call via telephone, please register via this link. Once registered, dial-in numbers and a PIN number will be provided. The slide presentation and audio of the webcast will be available via this link. Participants may also access the slides and the webcast of the conference call via the “Events & Presentations” page of the Investors' section of the Company’s website at www.BioNTech.com. 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. About BioNTechBiopharmaceutical New Technologies (BioNTech) is a global next generation immunotherapy company pioneering novel therapies for cancer and other serious diseases. BioNTech exploits a wide array of computational discovery and therapeutic drug platforms for the rapid development of novel biopharmaceuticals. Its broad portfolio of oncology product candidates includes individualized and off-the-shelf mRNA-based therapies, innovative chimeric antigen receptor (CAR) T cells, several protein-based therapeutics, including bispecific immune checkpoint modulators, targeted cancer antibodies and antibody-drug conjugate (ADC) therapeutics, as well as small molecules. Based on its deep expertise in mRNA vaccine development and in-house manufacturing capabilities, BioNTech and its collaborators are developing multiple mRNA vaccine candidates for a range of infectious diseases alongside its diverse oncology pipeline. BioNTech has established a broad set of relationships with multiple global and specialized pharmaceutical collaborators, including Biotheus, DualityBio, Fosun Pharma, Genentech, a member of the Roche Group, Genevant, Genmab, MediLink, OncoC4, Pfizer and Regeneron. For more information, please visit www.BioNTech.com. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, but not limited to, statements concerning: BioNTech’s expected revenues related to sales of BioNTech’s COVID-19 vaccine, referred to as COMIRNATY where approved for use under full or conditional marketing authorization, in territories controlled by BioNTech’s collaboration partners, particularly for those figures that are derived from preliminary estimates provided by BioNTech’s partners; the rate and degree of market acceptance of BioNTech’s COVID-19 vaccine and, if approved, BioNTech’s investigational medicines; expectations regarding anticipated changes in COVID-19 vaccine demand, including changes to the ordering environment and expected regulatory recommendations to adapt vaccines to address new variants or sublineages; the initiation, timing, progress, results, and cost of BioNTech’s research and development programs, including BioNTech’s current and future preclinical studies and clinical trials, including statements regarding the timing of initiation, enrollment, and completion of studies or trials and related preparatory work and the availability of results, and the timing and outcome of applications for regulatory approvals and marketing authorizations; BioNTech’s expectations regarding potential future commercialization in oncology, including goals regarding timing and indications; the targeted timing and number of additional potentially registrational trials, and the registrational potential of any trial BioNTech may initiate; discussions with regulatory agencies; BioNTech’s expectations with respect to intellectual property; the impact of BioNTech’s collaboration and licensing agreements; the development, nature and feasibility of sustainable vaccine production and supply solutions; BioNTech’s estimates of revenues, research and development expenses, selling, general and administrative expenses and capital expenditures for operating activities; and BioNTech’s expectations of net profit / (loss). In some cases, forward-looking statements can be identified by terminology such as “will,” “may,” “should,” “expects,” “intends,” “plans,” “aims,” “anticipates,” “believes,” “estimates,” “predicts,” “potential,” “continue,” or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. The forward-looking statements in this press release are based on BioNTech’s current expectations and beliefs of future events, and are neither promises nor guarantees. You should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties, and other factors, many of which are beyond BioNTech’s control and which could cause actual results to differ materially and adversely from those expressed or implied by these forward-looking statements. 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You should review the risks and uncertainties described under the heading “Risk Factors” in BioNTech’s Report on Form 6-K for the period ended June 30, 2024 and in subsequent filings made by BioNTech with the SEC, which are available on the SEC’s website at www.sec.gov. These forward-looking statements speak only as of the date hereof. Except as required by law, BioNTech disclaims any intention or responsibility for updating or revising any forward-looking statements contained in this press release in the event of new information, future developments or otherwise. Contacts Investor RelationsVictoria Meissner, M.D.+1 617 528 8293Investors@biontech.de Media Relations Jasmina Alatovic +49 (0)6131 9084 1513 Media@biontech.de Interim Consolidated Statements of Profit or Loss Three months ended June 30, Six months ended June 30, 2024 2023 2024 2023 (in millions €, except per share data) (unaudited) (unaudited) (unaudited) (unaudited) Revenues 128.7 167.7 316.3 1,444.7 Cost of sales (59.8) (162.9) (118.9) (258.9) Research and development expenses (584.6) (373.4) (1,092.1) (707.4) Sales and marketing expenses (12.9) (18.1) (28.5) (30.3) General and administrative expenses (1) (170.9) (119.8) (287.9) (231.6) Other operating expenses (1) (290.8) (77.1) (314.7) (202.8) Other operating income 24.1 20.3 52.4 77.4 Operating income / (loss) (966.2) (563.3) (1,473.4) 91.1 Finance income 167.7 152.4 345.3 208.9 Finance expenses (7.3) (1.3) (9.5) (4.5) Profit / (Loss) before tax (805.8) (412.2) (1,137.6) 295.5 Income taxes (2.0) 221.8 14.7 16.3 Profit / (Loss) for the period (807.8) (190.4) (1,122.9) 311.8 Earnings / (Loss) per share Basic earnings / (loss) for the period per share (3.36) (0.79) (4.67) 1.29 Diluted earnings / (loss) for the period per share (3.36) (0.79) (4.67) 1.28 (1) Adjustments to prior-year figures due to change in functional allocation of general and administrative expenses and other operating expenses. Interim Consolidated Statements of Financial Position June 30, December 31, (in millions €) 2024 2023 Assets (unaudited) Non-current assets Goodwill 372.4 362.5 Other intangible assets 862.3 804.1 Property, plant and equipment 868.6 757.2 Right-of-use assets 256.4 214.4 Other financial assets 1,386.1 1,176.1 Other non-financial assets 108.2 83.4 Deferred tax assets 102.3 81.3 Total non-current assets 3,956.3 3,479.0 Current assets Inventories 340.1 357.7 Trade and other receivables 75.8 2,155.7 Contract assets 3.9 4.9 Other financial assets 6,919.0 4,885.3 Other non-financial assets 359.3 280.9 Income tax assets 206.8 179.1 Cash and cash equivalents 10,376.7 11,663.7 Total current assets 18,281.6 19,527.3 Total assets 22,237.9 23,006.3 Equity and liabilities Equity Share capital 248.6 248.6 Capital reserve 1,232.3 1,229.4 Treasury shares (10.8) (10.8) Retained earnings 18,640.4 19,763.3 Other reserves (1,038.2) (984.6) Total equity 19,072.3 20,245.9 Non-current liabilities Lease liabilities, loans and borrowings 219.3 191.0 Other financial liabilities 42.1 38.8 Provisions 9.0 8.8 Contract liabilities 353.6 398.5 Other non-financial liabilities 77.9 13.1 Deferred tax liabilities 37.8 39.7 Total non-current liabilities 739.7 689.9 Current liabilities Lease liabilities, loans and borrowings 35.3 28.1 Trade payables and other payables 881.5 354.0 Other financial liabilities 146.0 415.2 Income tax liabilities 365.2 525.5 Provisions 363.9 269.3 Contract liabilities 474.3 353.3 Other non-financial liabilities 159.7 125.1 Total current liabilities 2,425.9 2,070.5 Total liabilities 3,165.6 2,760.4 Total equity and liabilities 22,237.9 23,006.3 Interim Consolidated Statements of Cash Flows Three months ended June 30, Six months ended June 30, 2024 2023 2024 2023 (in millions €) (unaudited) (unaudited) (unaudited) (unaudited) Operating activities Profit / (Loss) for the period (807.8) (190.4) (1,122.9) 311.8 Income taxes 2.0 (221.8) (14.7) (16.3) Profit / (Loss) before tax (805.8) (412.2) (1,137.6) 295.5 Adjustments to reconcile profit before tax to net cash flows: Depreciation and amortization of property, plant, equipment, intangible assets and right-of-use assets 49.9 31.9 88.2 63.3 Share-based payment expenses 20.2 13.1 36.5 21.7 Net foreign exchange differences (13.2) (397.0) (41.9) (343.9) (Gain) / Loss on disposal of property, plant and equipment (0.2) 0.1 (0.2) 0.3 Finance income excluding foreign exchange differences (167.7) (126.6) (342.6) (208.9) Finance expense excluding foreign exchange differences 4.8 1.3 9.5 2.5 Government grants (3.1) — (12.2) (3.0) Unrealized loss on derivative instruments at fair value through profit or loss(1) 5.0 124.0 6.7 200.2 Working capital adjustments: Decrease in trade and other receivables, contract assets and other assets(1) 1,599.6 4,137.0 2,097.8 5,030.8 Decrease / (Increase) in inventories 5.3 (24.8) 17.6 (9.3) (Decrease) / Increase in trade payables, other financial liabilities, other liabilities, contract liabilities, refund liabilities and provisions 760.8 592.7 472.8 (268.9) Interest received and realized gains from cash and cash equivalents 80.8 42.5 280.2 96.1 Interest paid and realized losses from cash and cash equivalents (1.6) (1.3) (5.3) (2.5) Income tax received / (paid), net(1) 66.4 437.3 (192.4) (407.6) Share-based payments (6.8) (31.3) (9.2) (757.0) Government grants received 32.8 — 42.0 — Net cash flows from operating activities 1,627.2 4,386.7 1,309.9 3,709.3 Investing activities Purchase of property, plant and equipment (88.6) (67.2) (147.1) (112.4) Proceeds from sale of property, plant and equipment 0.2 — 0.2 — Purchase of intangible assets and right-of-use assets (52.7) (242.1) (131.1) (251.7) Investment in other financial assets (2,448.2) (1,982.5) (7,343.3) (2,663.1) Proceeds from maturity of other financial assets 2,347.9 — 5,075.5 — Net cash flows used in investing activities (241.4) (2,291.8) (2,545.8) (3,027.2) Financing activities Repayment of loans and borrowings (2.3) — (2.3) — Payments related to lease liabilities (20.6) (9.4) (28.4) (18.7) Share repurchase program — (154.0) — (436.0) Net cash flows used in financing activities (22.9) (163.4) (30.7) (454.7) Net increase / (decrease) in cash and cash equivalents 1,362.9 1,931.5 (1,266.6) 227.4 Change in cash and cash equivalents resulting from exchange rate differences (3.3) 91.2 3.5 64.1 Change in cash and cash equivalents resulting from other valuation effects 40.5 — (23.9) — Cash and cash equivalents at the beginning of the period 8,976.6 12,143.9 11,663.7 13,875.1 Cash and cash equivalents as of June 30 10,376.7 14,166.6 10,376.7 14,166.6 (1) Adjustments to prior-year figures relate to reclassifications within the cash flows from operating activities.

作者｜与安 2024年上半年，已经有68起管线/产品交易案，整理如下（按时间排序）： 2024年上半年管线/产品交易案汇总 从汇总表格可见，在2024年上半年的药企产品合作案中，合作金额最大的三起案例为恒瑞医药 与 Hercules 在GLP-1组合药物的合作（60.35亿美元），诺华与舶望制药在SiRNA领域的合作(41.65亿美元)以及诺华与PeptiDream在PDC药物的合作（28.9亿美元）。此外，有多起合作案的金额超过了20亿或10亿美元，涉及肿瘤学、代谢性疾病、心血管疾病、神经系统疾病以及罕见病等多个治疗领域。 通过这些合作案，我们能够观察到一系列引人瞩目的趋势。首先，药企的合作不再局限于传统的肿瘤学和免疫疾病治疗领域，而是扩展到了包括代谢性疾病、神经系统疾病、心血管疾病以及罕见病在内的更广泛的治疗领域。 其次，创新技术的应用成为合作案中的一个显著特点。从RNA靶向药物到基因编辑，从小核酸疗法到PROTAC技术，再到抗体偶联药物，这些前沿技术在合作案中的频繁出现，突显了医药企业在研发新的治疗方法上所投入的努力和对未来治疗潜力的信心。 高额交易的频繁出现不仅反映了市场对创新药物的高度认可，也显示了医药企业对研发投入的巨大决心。许多合作案涉及多家跨国药企，这表明在全球医药行业中，通过合作共享资源和知识，加速新药研发已成为一种有效的策略。此外，一些合作案中还包含了股权投资，这种战略性的投资不仅为合作方提供了资金支持，也建立了更紧密的合作关系。 新兴市场的开拓也成为药企合作的一个新动向，药企正寻求在全球范围内的增长机会，行业合作和市场拓展正变得更加全球化。同时，一些企业采取了“联合出海”的新模式，这种模式通过与海外公司的合作，既获得授权许可费，又参与新公司的分成，为医药企业的国际化提供了新的思路。 下面我们将对这68项交易案进行详细的梳理，以供同行参考。   一月   [1] 13亿美元：诺华×Voyager Therapeutics 1月2日，诺华宣布与Voyager Therapeutics达成一项战略合作与许可协议，共同开发针对亨廷顿病（HD）和脊髓性肌萎缩症(SMA)的基因疗法。 本次合作的重点是Voyager公司专有的TRACER衣壳发现平台，该平台利用基于RNA的筛选方法，能够快速发现具有明显中枢神经系统（CNS）趋向性并能穿透血脑屏障的腺相关病毒（AAV）衣壳。据Voyager公司网站介绍，TRACER具有广泛的适用性，其产生的病毒衣壳可以调整为靶向神经元或神经胶质细胞，能够以较小剂量递送，并实现静脉注射。 根据协议条款，诺华将向Voyager支付1亿美元，其中包括以2000万美元购买Voyager 新发行的股权。此外，Voyager还有资格获得高达12亿美元的临床前、开发、监管和销售里程碑，以及基于TRACER衣壳的产品的全球净销售额的销售分成。 诺华将获得Voyager与SMA相关的TRACER衣壳的靶标独家使用权，并将负责所有开发和商业化。诺华还将利用Voyager的TRACER衣壳和专有有效载荷，获得Voyager用于HD的AAV基因疗法的全球权利。Voyager将负责临床前进展，诺华将负责HD项目的所有临床开发和商业化。 [2]10.5亿美元：罗氏×宜联生物 1月2日 ，苏州宜联生物宣布已与罗氏达成全球合作和许可协议，合作开发靶向间质表皮转化因子（c-MET）的下一代ADC候选产品YL211（c-MET ADC），用于治疗实体瘤。宜联生物将与罗氏中国创新中心（CICoR）共同合作推动YL211项目进入临床I期试验阶段，并交由罗氏负责后续全球范围内进一步开发和商业化工作。根据协议，罗氏将向宜联生物支付首付款及近期里程碑付款5000万美元，另外还有近10亿美元的开发、注册和商业化潜在里程碑付款，以及未来基于全球年度销售净额的销售分成。 据罗氏介绍，c-MET为受体酪氨酸激酶（RTK）家族的成员之一，与肿瘤的形成、侵袭性生长和转移密切相关，是治疗上皮间质转化的关键靶点。尽管包括ADC在内的多种c-MET靶向疗法对实体瘤患者已显示出疗效，但在全球范围内仍存在为患者提供更优治疗选择的机会，以解决巨大的未满足的医疗需求。 目前，YL211处于临床申报阶段，采用了宜联生物新一代ADC平台技术TMALIN，并配合以高特异性的c-MET抗体。YL211已在多种临床前肿瘤模型及安全性评价实验中展现出极具潜力的疗效及安全性。 [3]超20亿美元：勃林格殷格翰×瑞博生物 1月3日，苏州瑞博生物宣布与勃林格殷格翰（Boehringer Ingelheim，BI）携手合作，宣布将共同开发治疗代谢功能障碍相关脂肪性肝炎（MASH）的小核酸创新疗法。 BI表示，瑞博的RIBO-GalSTAR技术平台，能够特异性靶向肝细胞中的致病基因，选择性抑制其mRNA，从而开发小核酸疗法（RNAi）。该疗法有望靶向传统药物分子无法成药的靶点，达到治疗相应疾病的目标。 这一合作将把瑞博在siRNA药物领域早期研究和临床开发的领先经验与BI致力改善心血管、肾脏和代谢疾病（CRM）患者生活质量的承诺紧密结合。 [4]10亿美元：罗氏×Remix Therapeutics 1月3日，Remix Therapeutics宣布与罗氏达成合作，达成总额可能超过10亿美元的合作和许可协议。两家公司将利用Remix的REMaster药物发现平台，发现和开发调节RNA加工的小分子疗法。 根据协议，Remix将获得3000万美元的预付款，并有资格获得高达1200万美元的近期里程碑付款，以及高达10亿美元的临床前、临床、商业和销售里程碑付款以及销售分成。罗氏将拥有针对特定靶点开发的药物的专有权。Remix将与罗氏一起开展药物发现和临床前开发工作，罗氏将负责所有因此产生的产品的临床开发和商业化工作。 据介绍，REMaster™技术平台有助于识别RNA加工模式，利用这些发现来调节基因表达。Remix的创新治疗方法有可能改变从基因组中读取基因的方式，以纠正、增强或消除基因信息，从而从根源上解决致病因素。 [5]20亿美元：罗氏×MOMA Therapeutics 1月4日,MOMA Therapeutics宣布与罗氏达成战略合作和许可协议，MOMA提供给罗氏其专有的知识库平台KnowledgeBase，用于识别和开发在癌症细胞增殖和生存中起关键作用的新型药物靶点。此次合作将利用这一平台发现和靶向高动态（highly dynamic）创新精准肿瘤学靶点。此外MOMA将获得罗氏6600万美元的预付款，合计其他权益数额高达20亿美元。 KnowledgeBase平台集成了结构功能分析、先导化合物发现技术和计算赋能的先导化合物优化。利用了分子机器类中所有酶固有的一个关键漏洞，即依赖于协调良好的、逐步的构象变化。迄今为止，MOMA已经利用这个定制平台来加速ATPase靶标类别的药物发现，该类别具有大量经过基因验证的靶标，行业识别治疗上可行药物的努力受到动态蛋白质运动程度的阻碍。 [6]超10亿美元：诺和诺德×Flagship Pioneering旗下两家公司 1月4日，诺和诺德宣布，已分别与Flagship Pioneering旗下两家生物平台的Omega Therapeutics和Cellarity公司达成新药研究合作，开发用于肥胖管理的表观遗传药物和针对MASH的新型疗法。诺和诺德将负责所有研发费用，同时，每家公司的创新产品还有资格获得高达5.32亿美元的首付款和里程碑付款以及销售分成。 其中，诺和诺德与Omega的合作将利用Omega专有平台技术开发一种表观基因组控制器，旨在增强代谢活性，作为肥胖管理潜在新疗法；而与Cellarity的合作则旨在解开代谢功能障碍相关脂肪性肝炎（MASH）的新型生物驱动因子，并将利用Cellarity的平台开发针对该疾病的小分子疗法。 [7]超10亿美元：Avenzo Therapeutics×安锐生物 1月4日，安锐生物（Allorion）宣布与Avenzo Therapeutics达成转让协议，后者将在全球范围内（不包括大中华区）开发和商业化ARTS-021（Avenzo代码：AVZO-021）。这是一种潜在的“best-in-class”的细胞周期蛋白依赖性激酶2（CDK2）选择性抑制剂。作为协议的一部分，Avenzo还获得了计划于2025年初提交IND的额外临床前项目的独家选择权。根据协议条款，安锐生物将获得4000万美元的首付款，额外研发里程碑和商业化里程碑款项，以及销售分成，两个项目的潜在付款总额将会超过10亿美元。 CDK2因其在CCNE1扩增型癌症和CDK4/6抑制剂耐药型乳腺癌中表现出治疗潜力而成为具有广阔市场前景的靶点。安锐生物自主研发的ARTS-021在临床前研究中显示高度激酶选择性、良好药代动力学特性和潜在的最佳临床前药效。 ARTS-021对CDK2表现出纳摩尔级的抑制活性，并保留对其他CDK蛋白特别是CDK1这一毒性关键驱动因素的高选择性。在体内异种移植模型实验中，无论是单独使用还是与CDK4/6抑制剂联合使用，ARTS-021均表现出显著疗效。Avenzo表示，该药物正在美国的多中心进行Ⅰ期临床试验，用于治疗HR+/HER2-转移性乳腺癌和其他晚期实体瘤。 [8]超7亿美元：Galapagos×BridGene Biosciences 1月4日，BridGene Biosciences宣布与Galapagos签订战略合作与许可协议。根据合作协议， BridGene将利用其化学蛋白质组学平台IMTAC，发现针对合作靶点的新型小分子药物候选物。双方将合作推进这些分子成为临床候选物，而Galapagos拥有开发和商业化的独家权利。 BridGene专注于针对那些具有高价值、传统上被认为“难以成药”的靶点，为治疗各类疾病开辟新的途径。其特有的IMTAC技术平台不仅可以在活细胞中发现大量靶标（包括“不可成药”靶标）的小分子配体；而且可以与表型筛选技术结合以确定驱动表型变化及疾病发生的靶标。 这项临床前研究合作将专注于Galapagos指定的肿瘤靶点。Galapagos将向BridGene支付高达2700万美元的预付款和临床前研究里程碑付款，以及超过7亿美元的临床和商业里程碑付款。BridGene还有资格获得一定比例的销售分成。 [9]41.65亿美元：诺华×舶望制药 1月7日，上海舶望制药（ArgoBiopharma）宣布与诺华签订了两项独家许可与合作协议，合作开发多款心血管siRNA药物。 诺华将获得Ⅰ期临床项目开发和商业化的全球独家许可、针对心血管疾病的至多2个额外靶点的化合物潜在许可选择（第一份协议），以及一项治疗心血管疾病的Ⅰ/Ⅱa期临床项目在大中华区外的开发和商业化独家许可（第二份协议）。 根据协议条款，舶望将获得1.85亿美元的首付款，并有望获得潜在的期权和里程碑付款，以及一定比例的销售分成，潜在交易总金额高达41.65亿美元。 [10]17.45亿美元：礼来×Isomorphic Labs 1月7日，Isomorphic Laboratories（下称“Isomorphic Labs”）宣布，与礼来开展合作，针对多个靶点开发小分子治疗药物。该公司致力将AI应用于药物发现，通过AI优先的方法，建立强大的新生物现象预测和生成模型，以预测药物的性能和设计新分子。此次合作的重点在于Isomorphic Labs的新一代AlphaFold技术。 据该司介绍，新版AlphaFold与Iso开发的其他突破性人工智能模型的深度整合，能够更加精准地预测蛋白质的结构，预测精度可以达到原子级。同时，新一代AlphaFold还进一步扩大了覆盖范围，从蛋白质扩展到包括配体（小分子）、核酸（DNA和RNA）以及含有翻译后修饰（PTM）的分子等蛋白质数据库（PDB）中的几乎所有生物分子。 根据协议条款，Isomorphic Labs将获得4500万美元的预付款，并有资格获得高达 17 亿美元的基于绩效的里程碑付款。 [11]12.375亿美元：诺华×Isomorphic Labs 1月7日，Isomorphic Labs宣布的合作对象还包括诺华。此次合作同样基于新一代AlphaFold展开，针对3个未披露靶点开发小分子药物。根据协议，Isomorphic Labs将获得3750万美元前期付款，并有资格获得高达12亿美元的里程碑付款。 [12]金额未披露：强生旗下×Simcha Therapeutics 1月8日，Simcha Therapeutics宣布与强生旗下公司Janssen Biotech（现已更名为Johnson & Johnson Innovative Medicine）达成一项许可和选择权协议，把Simcha专有的抗诱饵白细胞介素-18（decoy resistant IL-18，DR-18）技术融入选定的CAR-T细胞疗法候选产品中。 根据协议条款，强生将负责开发、制造和商业化DR-18加强型细胞疗法的项目。Simcha将获得预付款，可能的选择权行使费用，以及依据开发和商业化进程的里程碑付款，具体金额未披露。 [13]1.143亿美元：Tome Biosciences×Genevant Sciences 1月16日，Genevant Sciences宣布与 Tome Biosciences 达成合作和非独家许可协议，将其专有的脂质纳米颗粒（lipid nanoparticle，LNP）技术与Tome的可编程基因组整合 （programmable genomic integration，PGI）技术相结合，以开发体内基因编辑疗法，用于治疗一种罕见单基因肝病，具体病名未公开。 根据协议条款，此次交易总价值达1.143亿美元，同时，Genevant还将对所开发药物的销售收取分成。 [14]2.2亿美元：默沙东×Unnatural Products 1月23日，Unnatural Products（UNP）宣布与默沙东达成合作。UNP是一家将AI与化学相结合的生物技术公司，其平台通过并行实验和机器学习的结合来解决大环领域药物化学的复杂性，致力实现下一代分子靶向疗法。 本次合作将利用UNP在AI和化学领域的技术，致力设计和开发针对肿瘤治疗靶点的大环类候选药物。根据协议条款，UNP将收到一笔未公开的预付款，并将有资格获得与候选产品的开发和商业化相关的里程碑付款，高达约2.2亿美元。 [15]6.44亿美元：罗氏旗下×GenEdit 1月23日，罗氏旗下公司基因泰克（Genentech）宣布，与基因疗法开发公司GenEdit达成合作，利用GenEdit的NanoGalaxy平台发现和开发新型亲水纳米颗粒（HNP），递送用于治疗自身免疫病的核酸药物。 根据协议条款，GenEdit将获得1500万美元预付款，并有资格在合作过程中获得总额高达6.29亿美元的近期、临床前和临床开发、商业和净销售额里程碑付款以及一定比例的销售分成。 [16]2.55亿美元：诺和诺德×EralCal Therapeutics 1月23日，EraCal Therapeutics宣布与诺和诺德达成一项合作和许可协议，以开发和商业化EraCal的口服小分子药物。EraCal研发了一种基于斑马鱼模型的表型筛选平台，通过该平台成功开发出能够精准作用、安全调节人体食欲的抗肥胖药物。该药物基于EraCal的平台技术发现，通过针对控制食欲和体重的新型作用机制来治疗肥胖。 根据协议条款，EraCal 将获得高达2.35亿欧元（2.55亿美元）的前期、开发和商业里程碑付款，以及产品上市后的销售分成，而诺和诺德将获得EraCal口服小分子药物的所有开发和商业化的独家权利。 [17]7亿美元：Glenmark Specialty S.A.×康宁杰瑞、思路迪医药 1月25日，康宁杰瑞与思路迪医药（3D Medicines）共同宣布，与Glenmark Pharmaceuticals子公司Glenmark Specialty S.A.（下称“GSSA”）达成协议。本次合作的重点在于PD-L1抗体药物恩维达（KN035），即恩沃利单抗注射液。该药物由康宁杰瑞自主研发，2016年起与思路迪医药共同开发。目前在中国、美国和日本针对多个肿瘤适应症同步开展临床试验，多个适应症已进入注册/Ⅲ期临床阶段。 2020年3月30日，康宁杰瑞、思路迪医药、先声药业三方达成战略合作，康宁杰瑞作为原研方负责生产和质量，思路迪医药负责肿瘤领域的临床开发，先声药业负责产品在中国大陆的独家商业推广。 通过此次授权，Glenmark将获得在印度、亚太地区（除新加坡、泰国、马来西亚）、中东和非洲、俄罗斯、独联体和拉丁美洲的肿瘤适应症开发和商业化独家许可权益。有关KN035开发及商业化费用由Glenmark自行承担。 根据协议， GSSA将支付首付款以及基于若干开发、监管及商业化进展的里程碑付款，金额共计7.008亿美元，并根据KN035净销售额，支付一定比例的销售分成。康宁杰瑞保留全球范围内为任何目的而生产KN035的独家权利。思路迪医药保留在该地区以外于肿瘤领域为任何目的开发及商业化KN035的权利。   二月   [18]2.5亿美元：BioNTech×Autolus 2月8日，BioNTech宣布与工程化T细胞疗法研发企业Autolus Therapeutics达成战略合作，共同推进双方多个自体CAR-T项目的商业化。此次合作中，双方签订了许可和期权协议以及证券购买协议。BioNTech将以私募方式购买2亿美元的Autolus美国存托股份，有权任命一名董事加入Autolus董事会，并向Autolus支付5000万美元现金。 据BioNTech介绍，该司将有权访问Autolus的商业和临床站点网络、英国的制造能力和商业供应基础设施，以加速BNT211在其他CLDN6+肿瘤类型中的开发。BioNTech 计划到2024年底进行10项或更多正在进行的潜在注册临床试验，包括其全资拥有的BNT211。此外，BioNTech还可以选择使用一套Autolus靶标结合剂和细胞编程技术，以支持其开发进展。 同时，BioNTech将支持Autolus先导细胞治疗候选药物obe-cel的启动和扩展开发计划，并获得销售分成，Autolus保留对obe-cel开发和商业化的全部权利和控制权。BioNTech还将为Autolus的AUTO1/22和AUTO6NG的开发提供支持，并提供联合商业化选项。 [19]8亿美元：Astellas×Kelonia 2月15日，Astellas宣布其子公司 Xyphos Biosciences与Kelonia Therapeutics 达成合并签订了许可协议，共同开发新型免疫肿瘤疗法。 本次合作的重点在于Kelonia的体内基因放置系统（iGPS）和Xyphos的ACCEL技术，iGPS使用下一代慢病毒颗粒技术将“遗传货物”有效精确地输送到患者体内所需的靶细胞，Xyphos则可使免疫细胞表达可转换的CAR，以靶向肿瘤细胞。 本次合作计划将Kelonia的iGPS与Xyphos的ACCEL技术相结合，共同开发至多两个体内 CAR-T 细胞疗法。根据协议条款，Xyphos将负责合作研究产品的开发和商业化。Kelonia将获得第一个项目的4000万美元预付款，如果Xyphos行使第二个项目的选择权，将获得额外的3500万美元，潜在的里程碑和应急付款，总额达近8亿美元。此外，Kelonia将获得合作项目的研发资金，并有资格获得销售分成。 [20]超6400万美元：艾伯维×Tentarix Biotherapeutics 2月22日，艾伯维宣布与Tentarix Biotherapeutics达成一项为期多年的合作。此次合作的重点在于Tentarix专有的Tentacles平台，通过将艾伯维在肿瘤学和免疫学方面的专业知识与Tentarix的Tentacles™平台相结合，双方将共同致力发现和开发肿瘤学和免疫学中的条件活性、多特异性生物候选药物。 根据协议条款，Tentarix将获得两个项目的预付款，总额为6400万美元。艾伯维将获得独家选择权，以在候选人提名后完全收购这些项目，并为每个项目支付额外的未公开付款。 [21]负责试验相关款项：Immunocore×百时美施贵宝 2月22日，Immunocore宣布与百时美施贵宝（BristolMyers Squibb，BMS）达成临床试验合作和供应协议，两者将共同研究Immunocore现货型T细胞受体（TCR）双特异疗法IMC-F106C与PD-1抑制剂Opdivo（nivolumab）联合，用于一线治疗晚期黑色素瘤的疗效与安全性。 根据合作条款，Immunocore将负责IMC-F106C与Opdivo联合用于一线治疗晚期皮肤黑色素瘤的Ⅲ期临床试验（PRISM-MEL-301）的相关款项，百时美施贵宝则将提供Opdivo。据Immunocore介绍，该试验将随机分配HLA-A*02:01阳性的一线晚期皮肤黑色素瘤患者，接受IMC-F106C + Opdivo的治疗，以Opdivo单药或Opdivo+relatlimab（LAG-3靶向单抗）固定剂量组合为对照组，具体情况取决于患者入组的国家与地区。该司计划于2024年第一季度进行首例患者给药。 [22]14.6亿美元：诺和诺德×Neomorph 2月26日，Neomorph宣布与诺和诺德达成合作和许可协议，开展多靶点合作，以发现、开发和商业化用于心脏代谢和罕见疾病的新型分子胶降解剂。Neomorph表示，此次合作通过将其专有的分子胶发现平台与诺和诺德在心脏代谢和罕见疾病方面的丰富经验相结合，有望在这些领域开发变革性疗法，也将使其平台应用扩展至新的治疗领域。 根据协议条款，Neomorph将获得预付款、近期里程碑付款以及研发资金，同时还有资格获得未来的临床、商业和销售里程碑付款，潜在交易总价值达到14.6亿美元，外加销售分成。Neomorph将负责针对选定靶点的发现和临床前活动，诺和诺德有权独家寻求化合物的进一步临床开发和商业化。 [23]7.13亿美元：艾伯维×OSE Immunotherapeutics 2月28日，艾伯维宣布与OSE Immunotherapeutics SA（下称“OSE”）建立战略合作伙伴关系。本次合作重点在于开发OSE-230，以扩大艾伯维在免疫学方面的产品组合，助力提高炎症性疾病患者的护理标准。OSE-230是一种“first-in-class”的单克隆抗体，旨在激活G蛋白偶联受体（GPCR）靶标ChemR23——这可能为解决慢性炎症、调节巨噬细胞和中性粒细胞的功能提供一种新的机制。目前，该药物正处于临床前开发阶段。 根据协议条款，艾伯维将获得开发、制造和商业化OSE-230的全球独家许可。OSE将获得4800万美元的预付款，并有资格在临床开发、监管和商业里程碑方面获得高达6.65亿美元的额外资金。此外，OSE将有资格获得基于OSE-230全球净销售额的销售分成。 [24]3.5亿美元：Viatris×Idorsia 2月28日，Idorsia宣布和Viatris达成全球研发合作交易，Viatris将获得两款药物的全球开发和商业化权益，即用于急性心肌梗死（AMI）的P2Y12抑制剂Selatogrel和用于系统性红斑狼疮(SLE)的口服S1P1受体抑制剂Cenerimod，其中Cenerimod的全球开发和商业化不包括日本、韩国和亚太地区的某些国家。此外，Viatris还对Idorsia拥有的其他资产拥有优先谈判权。目前，两款药物均处于Ⅲ期临床试验阶段。 根据协议条款，双方将共同承担开发成本。Vistris将支付Idorsia 3.5亿美元的预付款、潜在的开发和监管里程碑等款项，以及销售里程碑和一定比例的销售分成，并在交易完成时，将72名开发项目的相关员工转移到Viatris。   三月   [25]7.56亿美元：德国默克×C4 Therapeutics 3月4日，C4 Therapeutics（下称“C4T”）宣布已与德国默克（Merck KGaA）签订许可和合作协议， 利用C4T的专有平台TORPEDO，合作发现两种针对关键致癌蛋白的靶向蛋白质降解剂。 根据协议条款，C4T则将获得1600万美元的预付款，并有可能获得高达约 7.4 亿美元的发现、监管和商业里程碑付款。此外，C4T还有资格在各项目的未来销售中获得销售分成。德国默克公司将资助C4T的发现研究工作，并负责候选药物的临床开发和商业化。 [26]3.1亿美元：拜耳×BridgeBio Pharma 3月4日，BridgeBio Pharma和拜耳（Bayer）宣布建立合作伙伴关系。本次合作的重点是BridgeBio的Acoramidis（AG10），这是一种具有口服活性的、选择性的甲状腺素转运蛋白 (transthyretin，TTR ) 的稳定剂，用于治疗转甲状腺素蛋白淀粉样心肌病（ATTR-CM）。 据BridgeBio介绍，Acoramidis是一款新一代口服高效转甲状腺素蛋白（TTR）小分子稳定剂，旨在模拟具有保护作用的TTR T119M突变的功能，维持TTR蛋白的正常四聚体构象，防止具有毒性的淀粉样蛋白的产生。目前已在美进入NDA阶段，预定PDUFA行动日期为2024年11月29日；此外，欧洲药品管理局（EMA）也已接受acoramidis的上市许可申请（MAA）。 根据协议条款，拜耳将获得Acoramidis在欧洲商业化的独家许可，BridgeBio将获得高达3.1亿美元前期付款和近期里程碑等款项。 基因组重编码生物体（GROs） [27]15.81亿美元：吉利德×Merus 3月6日，吉利德（Gilead）和Merus N.V.（下称“Merus”）宣布达成一项合作、选择权和许可协议，以发现靶向三特异性抗体的新型双肿瘤相关抗原（TAA）。通过使用Merus专有的Triclonics平台，双方将研究和开发多个独立的临床前研究项目。 本次合作的重点在于Merus的专有平台Triclonics，通过结合吉利德的肿瘤学专业知识，双方将共同开发多个独立的临床前研究项目。据介绍，Merus将推进两个项目的早期研究活动，并可选择进行第三个项目。吉利德将有权在完成选定的研究活动后，获得合作项目许可。 根据协议条款，Merus将获得5600万美元的预付款，以及吉利德对Merus普通股的2500万美元股权投资。在所有潜在项目中，Merus还有资格获得高达15亿美元的资金，包括额外的短期和期权付款、潜在的开发和商业化里程碑付款，以及潜在的销售分成。对于第三个潜在项目，Merus可以选择分享净利润和净亏损的50/50分成，以代替未来的里程碑和销售分成。 [28]8.09亿美元：勃林格殷格翰×Sosei Heptares 3月11日，BI和Sosei Heptares（下称“Sosei”）宣布，双方已达成全球合作和独家许可选择权协议。本次重点旨在共同开发和商业化Sosei的“First-in-class” GPR52激动剂组合（一种新型GPCR靶点），以求通过同时解决精神分裂症的阳性、阴性和认知症状，提供一种新的精确疗法，同时改善患者预后。这是基于受体在大脑中驱动阳性（纹状体）和阴性与认知症状（前额叶皮层）的两个区域中的位置。GPR52激动作用使纹状体平静，同时增强额叶皮质功能，从而进一步提高治疗的精确性。 通过此次合作，Sosei Heptares将获得2500万欧元（2679万美元）的预付款，并有资格获得6000万欧元（6429万美元）的期权行权付款，以及总额高达6.7亿欧元（7.18亿美元）的进一步开发、监管和商业化里程碑付款，以及未来产品销售的临床阶段资产的惯常销售分成。 [29]10亿美元：默沙东×Pearl Bio 3月12日，Pearl Bio宣布与默沙东签署了许可、合作和选择权协议。本次合作重点在于Pearl Bio独家的GRO（Genomically Recoded Organisms）技术，并利用其在细胞基和无细胞系统中的研发能力和专有的连接核糖体来编码合成单体，靶向此前无法接近的表位，发现和开发用于治疗癌症的生物疗法。 据Pearl Bio介绍，该司汇集了独家平台技术，通过编码合成化学物质来推进多功能化生物制剂和生物材料。此次合作，双方将致力于开发具有可调性质的多功能治疗候选药物，解决生物药物面临的一些关键缺陷。 根据协议，Pearl有资格获得总计高达10亿美元的预付款，期权和里程碑付款，并可能获得获批产品的一定比例的销售分成。 [30]金额未披露：Allogene Therapeutics×Arbor Biotechnologies 3月12日，Allogene Therapeutics（下称“Allogene”）和Arbor Biotechnologies（下称“Arbor”）宣布达成一项全球独家基因编辑许可协议，将Arbor专有的CRISPR基因编辑技术用于Allogene的下一代AlloCAR T平台，用于治疗自身免疫性疾病（AID）。 凭借其在CAR-T细胞疗法领域的专业知识和深厚经验，Allogene致力于设计出创新性的同种异体CAR-T产品。据悉，Allogene的首个AID AlloCAR T研究产品预计将于2025年初进入Ⅰ期临床试验。 [31]金额未披露：勃林格殷格翰×上海莱士 3月13日，BI宣布与上海莱士血液制品有限公司（下称“上海莱士”）达成合作，重点聚焦上海莱士旗下的血友病创新药物SR604注射液。SR604注射液是一种人源化高亲和力结合人活化蛋白C，特异性抑制人活化蛋白C抗凝血功能的单克隆抗体制剂。 目前，该药物处于I期临床试验阶段（CTR20241608），有望为血友病及先天性凝血因子VII缺乏症患者的出血预防提供全新的治疗选择。据BI介绍，截至目前，全球尚无与该药物同靶点的产品上市。 此次合作，BI中国生物制药将为SR604注射液项目提供生产工艺转移、原液和制剂cGMP生产及CMC申报文件撰写全流程服务，以期通过国际一流CDMO平台转化为优质终端产品。 [32]金额未披露：艾伯维×Parvus Therapeutics 3月20日，Parvus Therapeutics（下称“Parvus”）宣布与艾伯维签订了一项独家全球许可合作和期权协议。本次合作聚焦Parvus的Navacim平台技术，旨在通过该平台开发和商业化炎症性肠病（IBD）的新疗法。 这是一种调节性T细胞（Treg）免疫耐受平台技术，有可能阻止和治愈自身免疫性疾病。Navacims 向T细胞呈递多价肽-MHC，从而触发T细胞的内源性扩增和分化为抗原特异性调节性T细胞（Tregs），从而在不损害对感染和癌症的正常免疫力的情况下提供潜在的治愈性器官特异性免疫耐受。 通过此次合作，艾伯维将获得通过该平台开发的IBD疗法的开发和商业化全球独家选择权。根据协议条款，Parvus将获得预付款和潜在的股权投资，并有资格获得下游开发和商业里程碑付款以及未来产品的销售分成。 [33]6.475亿美元：吉利德×Xilio Therapeutics 3月28日，吉利德和Xilio Therapeutics（下称“Xilio”）宣布达成独家许可协议，开发和商业化Xilio的肿瘤激活IL-12项目XTX301。 XTX301 是一种研究性肿瘤激活的 IL-12，旨在有效刺激抗肿瘤免疫，并将免疫原性差的“冷”肿瘤的肿瘤微环境（TME）重新编程为发炎或“热”状态。目前，该药物处在Ⅰ期临床试验阶段，评估其作为晚期实体瘤患者单药治疗的安全性和耐受性。 根据协议条款，吉利德将获得开发和商业化Xilio的肿瘤激活IL-12XTX301的全球独家许可。Xilio则将收到4350万美元的预付款，其中包括3000 万美元的现金和吉利德以1350万美元的溢价对Xilio普通股的初始股权投资。同时，Xilio还将有资格获得高达6.04亿美元的额外或有付款，包括吉利德的额外股权投资、过渡费、特定的开发、监管和基于销售的里程碑付款，以及未来净产品销售额的销售分成。 [34]金额未披露：康哲药业×Incyte 3月31日，康哲药业通过其全资附属公司康哲美丽与Incyte就开发和商业化选择性口服JAK1抑制剂Povorcitinib订立了合作和许可协议，获得其在中国大陆、港澳台及东南亚十一国的研究、开发、注册及商业化产品的独家许可权利，以及在以上区域内生产该产品的非独家许可权利。 Povorcitinib是一种选择性口服小分子JAK1抑制剂，用于治疗非节段型白癜风、化脓性汗腺炎（HS）、结节性痒疹（PN）、哮喘和慢性自发性荨麻疹等自身免疫性和炎症性皮肤病。目前该药物在海外进行非节段型白癜风和HS的Ⅲ期临床试验，治疗PN、哮喘和慢性自发性荨麻疹的Ⅱ期临床试验也在进行中。 根据许可协议，康哲药业将向Incyte支付首付款，Incyte有权获得额外潜在的开发和商业化里程碑金以及基于许可产品在区域内净销售额的销售分成。   四月   [35]9亿美元：益普生 × Sutro Biopharma 4月2日，益普生和Sutro Biopharma（下称“Sutro”）宣布针对后者的STRO-003达成独家全球许可协议。该药物是一种处于临床前开发最后阶段的抗体-药物偶联物（ADC），靶向ROR1肿瘤抗原。ROR1被认为是具有广谱抗癌潜力的新药靶点，在正常细胞中多是低表达与不表达，在多种恶性肿瘤（如实体瘤和血液系统恶性肿瘤等）中却存在过表达。 此次合作中，Ipsen将获得开发和商业化STRO-003的全球独家权利，并将成为Ipsen产品组合中的首个ADC候选药物。根据协议条款，Ipsen将负责I期准备活动，包括提交研究性新药（IND）申请，以及所有后续的临床开发活动和全球商业化。Sutro Biopharma则有资格获得高达9亿美元的潜在前期、开发、监管和商业里程碑付款，包括股权投资、销售分成以及约9000万美元的近期付款。 [36]金额未披露：勃林格殷格翰×中国生物制药 4月8日，中国生物制药与BI宣布签署战略合作协议。利用双方优势和资源，共同在中国内地研发和商业化BI的肿瘤药物管线。 根据协议条款，此次合作涉及BI多个处于临床阶段的资产，包括三个处于临床开发阶段的资产Brigimadlin，Zongertinib和DLL3/CD3双特异性T细胞衔接器，以及若干早期临床资产。 其中，Brigimadlin 是一种鼠双微体同源基因2（MDM2）-p53拮抗剂，现已进入治疗去分化脂肪肉瘤的关键试验阶段，同时，该药物还被研究用于治疗胆道腺癌、非小细胞肺癌、胰腺癌和其他具有MDM2扩增的肿瘤。目前，FDA已授予 Brigimadlin 治疗去分化脂肪肉瘤的快速通道认定，和治疗胆道癌的孤儿药认定。Zongertinib是一种选择性HER2抑制剂，能与野生型和突变型HER2受体（包括20号外显子突变）的酪氨酸激酶结构域（TKD）共价结合。HER2 TKI 选择性的提高可能会带来更好的耐受性和疗效。目前，FDA 已授予Zongertinib 快速通道认定，作为一种研究性口服治疗药物，用于治疗HER2 突变且在铂类药物治疗期间或之后疾病进展的非小细胞肺癌患者。 而DLL3/CD3双特异性T细胞衔接器则处于II期试验阶段，用于治疗小细胞肺癌和其他神经内分泌癌。临床前研究结果表明，DLL3/CD3 单药可以有效抑制 DLL3 阳性的小细胞肺癌异种移植模型的生长，并呈剂量依赖性和时间依赖性。现已被FDA授予快速通道认定，用于治疗表达DLL3的晚期或转移性肺大细胞神经内分泌癌（LCNEC-Lung）患者，这些患者至少接受过一种既往含铂治疗并出现疾病进展，同时也被授予治疗小细胞肺癌的孤儿药认定。 [37]金额未披露：阿斯利康×勤浩医药 4月9日，勤浩医药宣布与阿斯利康建立临床研究合作，共同探索SHP2抑制剂GH21联合甲磺酸奥希替尼治疗非小细胞肺癌（NSCLC）。这是一项开放性、多中心、Ib/II期研究，旨在评估联合治疗在伴有表皮生长因子受体（EGFR）突变的晚期NSCLC患者中口服给药的安全性、耐受性、药代动力学和初步有效性，目前已于完成首次给药。 GH21是靶向SHP2的小分子抑制剂，对多种SHP2点突变体有效。勤浩医药表示，根据体内外研究结果，GH21脱靶风险低、口服生物利用度高，具有较大的安全窗，是一个极具开发潜力的小分子抗肿瘤药物。非临床研究表明，GH21单药或和其他抗肿瘤药联合用药，对多种实体肿瘤有效。 [38]11.6亿美元：诺华×Arvinas 4月11日，Arvinas宣布与诺华达成独家战略许可协议。本次交易聚焦Arvinas的ARV-766，这是一款用于前列腺癌患者的第二代PROTAC雄激素受体（AR）口服降解剂。同时，Arvinas的临床前AR-V7项目也将一并出售给诺华。 根据交易协议条款，诺华将负责ARV-766的全球临床开发和商业化，并将获得临床前AR-V7项目的所有研究、开发、制造和商业化权利。Arvinas则将获得总额为1.5亿美元的预付款，并有资格获得高达10.1亿美元的额外开发、监管和商业里程碑，以及一定比例的销售分成。 [39]19.35亿美元：艾伯维×Medincell 4月16日，艾伯维宣布与Medincell达成合作协议，共同研发下一代长效注射疗法。本次合作旨在利用Medincell的长效技术平台开发6款不同适应症的药物，并推进其商业化进程。 艾伯维将为每个项目提供资金支持，负责相关项目的临床开发、监管审批、生产及商业化等环节。Medincell将负责开展配方活动、临床前研究以及支持性CMC工作，以推动候选药物顺利进入临床试验阶段。 根据协议条款，艾伯维将支付3500万美元预付款，里程碑金额高达19亿美元（每个项目3.15亿美元），以及一定比例的销售分成。 [40]13.3亿美元：中国金桔×武田 4月16日，中国金桔生物科学（Kumquat Biosciences，下称“金桔”）宣布与武田（Takeda）达成独家战略合作，共同开发和商业化一种新型免疫调节癌症小分子抑制剂。 根据协议条款，武田将获得全球独家许可。根据金桔的选择，武田将承担并资助所有开发和商业化活动（除由金桔主导的Ⅰ期试验活动外）。金桔将获得高达1.3亿美元的近期付款，并可能获得超过12亿美元的临床、监管和商业里程碑等款项，以及产生的任何商业产品基于潜在净销售额的销售分成。 [41]18亿美元：益普生×Skyhawk Therapeutics 4月22日，益普生和Skyhawk Therapeutics宣布签署了一项全球独家合作协议，致力发现和开发调节罕见神经系统疾病的RNA靶向的新型小分子药物。通过此次合作，益普生将获得开发成功开发候选药物（DC）的全球权利的独家许可。在DC提名成功后，Ipsen将负责所有活动。Skyhawk的独特平台加速了在多个治疗领域（包括罕见神经系统疾病）构建 RNA 靶向小分子。 本次合作过程中，Skyhawk负责临床前开发，益普生则负责后续临床开发和商业化。根据协议条款，Ipsen将获得Skyhawk开发的两款候选药物的全球权益。Skyhawk则有资格获得高达18亿美元的开发、监管和商业里程碑，包括期权和研究合作的预付款，以及潜在的销售分成。 [42]超10亿美元：勃林格殷格翰×赭石生医 4月22日，BI宣布与赭石生医（Ochre Bio）达成合作，共同致力发现和开发针对慢性肝病（CLDs）的新型“first-in-class”再生疗法。 此次合作主要计划利用赭石生医的独特人类数据库和疾病模型，以加速开发和验证新型肝病靶点。赭石生医将利用其专利药物发现平台，将机器学习与人类大数据相结合，加上先进的成像和深度基因组表现型分析、自有的RNA化学研究以及应用专利的体外人体器官灌注模型的独家技术，促进对多个治疗慢性肝病的创新再生靶点的鉴定、表征分析和验证。 在这项多年期、多靶点的合作开发项目中，赭石生医将获得3500万美元的预付款和近期里程碑款项。赭石生医还将获得基于临床研究、药物注册和商业化成功的里程碑付款以及上市产品的销售分成，总交易金额预计超过10亿美元。 [43]4.7亿美元：再生元×Mammoth Biosciences 4月25日，再生元制药公司（Regeneron）和Mammoth Biosciences（下称“Mammoth”）宣布达成合作，共同开发和商业化基于体内CRISPR的基因编辑疗法，旨在靶向多种组织和细胞类型。 再生元正在开发腺相关病毒（AAV）载体，使用基于抗体的靶向技术来增强将基因疗法有效载荷递送至特定组织和细胞类型的能力。Mammoth则正在开发新型超紧凑核酸酶（ultracompact nucleases）和相关基因编辑系统。这些系统具有多种编辑功能，其尺寸却显著小于其他基于CRISPR的系统（包括第一代Cas9核酸酶）。通过将双方知识和深厚积累相结合，研发团队将努力创造可以递送至肝脏以外的组织的疾病修饰药物，实现该疗法应用范围的新突破。 根据协议条款，Mammoth将获1亿美元，其中包括签约时的9500万美元股权投资和预付款，并有资格获得每个目标高达3.7亿美元的开发、监管和商业里程碑付款，以及所有合作产品未来净销售额的一定比例的销售分成。此外，Mammoth可选择通过共同资助并分享大部分合作项目的收益来替代里程碑等付款。同时，在五年半的期限内，再生元将获得Mammoth编辑技术的广泛使用权（某些靶点除外），并且可以选择在支付额外的研究延期费用后将使用权延长两年。双方将共同挑选和研究合作靶点，随后由再生元负责领导其开发和商业化过程。 [44]金额未披露：圣诺医药旗下×华兰生物 4月26日，圣诺医药（Sirnaomics）宣布其非控股子公司达冕生物（RNAimmune）与华兰生物疫苗股份有限公司（下称"华兰生物"）达成战略合作，旨在推动针对呼吸道合胞病毒(RSV)的mRNA疫苗RV-1770在中国的临床开发和商业化。 RV-1770 是一款包含专有脂质纳米颗粒制剂配方的mRNA疫苗，专门用于预防成年人RSV病毒感染。这款创新型RSV mRNA疫苗，采用了近期分离出的RSV临床毒株序列，并应用独特AI增强序列的骨架设计。在临床前的棉鼠模型研究中，RV-1770展示出同时对RSV A亚型和B亚型病毒株的免疫反应及中和作用，并具有很好的安全性。其新药临床试验（IND）申请已于2023年12月获得FDA批准。 通过此次合作，达冕生物将获得来自华兰生物的预付款、里程碑付款和销售分成，华兰生物则将获得RV-1770在中国开发、产业化和商业化的独家许可。 [45]18.65亿美元：百时美施贵宝×Repertoire Immune Medicines 4月29日，Repertoire Immune Medicines（下称“Repertoire”）宣布与BMS达成多年战略合作，通过重置免疫系统，开发针对多达三种自身免疫性疾病的耐受性疫苗，为患有自身免疫性疾病的患者提供有效疗法。 本次合作的重点在于Repertoire的T细胞受体（TCR）表位发现平台 DECODE。通过利用DECODE和其专有的脂质纳米颗粒递送技术，双方致力发现和开发耐受性疫苗开发候选疫苗。此外，Repertoire还将使用DECODE来监测患者在临床开发过程中对耐受性疫苗的免疫反应，以验证其疫苗药效学效应。 根据协议条款，Repertoire将获得6500万美元预付款，以及高达18亿美元的开发、监管和商业里程碑款项，以及销售分成。Repertoire将负责所有关于该疫苗的活动，直至开发候选药物提名，而BMS则将获得耐受性疫苗的全球独家许可，负责其临床开发、监管事务和商业化。 [46]28.9亿美元：诺华×PeptiDream 4月30日，PeptiDream宣布扩大与诺华的肽发现合作。这项新协议扩展了2019年宣布的肽-药物偶联物（PDC）合作，最初于2010年启动，后续多次扩展。 PeptiDream的肽发现平台系统（PDPS）可以生成高度多样化的多肽库，并从库中高效地鉴定出针对指定靶标具有高亲和力和选择性的大环肽。根据多项目协议，针对诺华选择的靶标，PeptiDream将使用该技术来识别和优化的新型大环肽，以与放射性核素（RLT）或其他用于治疗和诊断目的的应用进行潜在结合， 根据协议条款，PeptiDream将获得280.3亿日元（1.8亿美元）的预付款。根据特定开发、监管和商业里程碑的实现情况，PeptiDream还将有资格获得高达4220.3亿日元（27.1亿美元）的付款，加上合作产生的任何此类产品的销售分成。   五月   [47]双方往来4.86亿美元：Gossamer Bio×Chiesi Farmaceutici 5月7日，Gossamer Bio（下称“Gossamer”）和Chiesi Farmaceutici（下称“Chiesi”）宣布达成全球合作与许可协议。在本次合作中，双方将共同开发和商业化Gossamer的Seralutinib，即一种用于治疗肺动脉高压（PAH）以及间质性肺病相关肺动脉高压（PH-ILD）的药物。 Seralutinib是一种吸入PDGFRα/β、CSF1R和c-KIT抑制剂，旨在通过干粉吸入器给药，用于肺动脉高压的潜在治疗。在 PAH 患者的Ⅱ期TORREY研究获得积极结果后，Gossamer于2023年启动了Ⅲ期PROSERA研究。本次合作中，双方计划在 2025 年年中启动一项针对 PH-ILD 的全球Ⅲ期注册研究，并评估 Seralutinib 在高度未满足医疗需求的其他适应症中的疗效。 Gossamer将继续主导Seralutinib在PAH和PH-ILD领域的全球开发，双方平均分摊除PROSERA研究外的开发成本，Gossamer继续承担财务责任。同时，两家公司将在美国市场平均分享商业利润和损失。Gossamer负责美国市场的商业化，包括负责50%的商业活动以及 PAH 和 PH-ILD 的销售预订，Chiesi则将主导其他适应症的在美商业化。 根据协议条款，Chiesi将向Gossamer支付1.6亿美元作为开发补偿，获得在美以外商业化Seralutinib的独家权利。Gossamer则将有资格获得高达1.46亿美元的监管里程碑和1.8亿美元的销售里程碑，以及在美国以外净销售额的销售分成。 [48]6亿美元：诺和诺德×Pioneering孵化Metaphore Biotechnologies 5月9日，诺和诺德与Flagship Pioneering孵化的生物技术公司Metaphore Biotechnologies达成合作，旨在开发一系列针对心脏代谢和罕见疾病的新型治疗方法，共同开发至多两种下一代肥胖治疗药物。 此次合作聚焦Metaphore的MIMIC平台。该平台旨在系统地分离具有单个氨基酸分辨率的药效团，设计分子模拟物，然后通过微调的治疗特性（包括功能、特异性、选择性和多靶点）优化分子。合作目标是设计针对GLP-1受体和相关生物学的多靶点疗法，旨在创造可扩展的不需要频繁给药的长效药物。Metaphore将与Pioneering Medicines（Flagship的内部药物开发和合作部门）及诺和诺德合作，通过基础活动和临床前开发来推进相关项目，后续诺和诺德可将这些项目推进到临床研究阶段。 根据协议条款，诺和诺德预计支付高达6亿美元的前期、开发和商业里程碑付款，以及授权产品年净销售额的销售分成，由Metaphore和Pioneering Medicin共享。诺和诺德还将报销研发成本，并参与Metaphore未来的融资。 [49]1.5亿美元：盐野义×Maze Therapeutics 5月10日，盐野义（Shionogi）与Maze Therapeutics（下称“Maze”）宣布，针对后者开发的MZE001达成一项独家许可协议。这是一种研究性口服糖原合酶1（GYS1）抑制剂，旨在通过限制致病糖原的积聚来治疗庞贝病。MZE001的Ⅰ期研究结果表明，该药物有可能成为治疗庞贝病的第一种口服疗法。 根据协议条款，盐野义将获得MZE001及相关程序和知识产权的全球独家权利。盐野义将支付1.5亿美元的预付款，Maze将有资格根据开发、监管和商业成就获得里程碑付款，以及基于未来净销售额的销售分成。 [50]10.55亿美元：赛诺菲×Fulcrum Therapeutics 5月13日，Fulcrum Therapeutics宣布与赛诺菲就Losmapimod的开发和商业化权益达成授权合作协议。 Losmapimod是一款口服小分子抑制剂，正在开发用于治疗面肩肱型肌营养不良症（FSHD），目前处于III期临床阶段。公司预计将于2024年第四季度公布其全球Ⅲ期REACH临床试验主要数据，并计划在美国、欧洲、日本和其他地区递交上市申请。 赛诺菲将获得在美国境外独家商业化losmapimod的权利。根据协议条款，Fulcrum 将获得 8000 万美元的预付款，并有资格基于监管和销售的里程碑中额外获得高达 9.75 亿美元的潜在付款，以及一定比例的销售分成。 [51]20.15亿美元：艾伯维×Gilgamesh Pharmaceuticals 5月13日，艾伯维宣布与Gilgamesh Pharmaceuticals（下称“Gilgamesh”）达成一项合作和授权选择协议，开发针对精神疾病的下一代疗法。此次合作将结合艾伯维在精神病学领域的专长与Gilgamesh的创新研究平台，以发现新型神经重塑剂（neuroplastogens）。 根据协议条款，艾伯维和Gilgamesh已同意研究和开发下一代精神疾病疗法组合。行使选择权后，艾伯维将负责开发和商业化活动。Gilgamesh将从艾伯维获得6500万美元的预付款，并有资格获得高达19.5亿美元的期权费和里程碑总额，以及净销售额的一定比例的销售分成。 [52]超21亿美元：武田×AC Immune 5月14日，武田宣布与AC Immune达成合作，针对后者的靶向有毒形式淀粉样蛋白β（Aβ）的免疫疗法（包括用于治疗阿尔茨海默病的ACI-24.060），签署了全球独家选择和许可协议。 ACI-24.060 是一种抗 Abeta 活性免疫治疗候选药物，旨在诱导针对被认为可驱动斑块形成和阿尔茨海默病进展的毒性形式的 Abeta 产生强大的抗体反应。通过诱导斑块清除和有效抑制大脑中斑块形成，ACI-24.060有可能延缓或减缓阿尔茨海默病的进展。ACI-24.060 正在正在进行的 ABATE 随机、双盲、安慰剂对照 1b/2 期试验中进行研究，以评估研究性免疫疗法在前驱阿尔茨海默病患者和唐氏综合征成人患者中的安全性、耐受性、免疫原性和药效学效应。 AC Immune将负责完成ABATE试验。在期权行使后，武田将进行并资助所有进一步的临床开发，并负责所有全球监管活动以及全球商业化。根据协议条款，AC Immune将获得1亿美元的预付款，如果所有相关里程碑在协议期间实现，则有资格获得期权行权费和高达约21亿美元的额外潜在开发、商业和销售里程碑。商业化后，AC Immune将有权获得全球净销售额的一定比例的销售分成。 [53]60.35亿美元：恒瑞医药×Hercules 5月16日，恒瑞医药发布公告，宣布将具有自主知识产权的 GLP-1 产品组合有偿许可给 Hercules CM Newco,Inc.（下称“Hercules”），Hercules将获得在除大中华区以外的全球范围内开发、生产和商业化 GLP-1 产品组合的独家权利。恒瑞将取得Hercules19.9%的股权，且将收取GLP-1产品组合授权许可费。 本次交易的GLP-1产品组合包括小分子GLP-1受体激动剂HRS-7535、多肽GLP-1R/GIPR双靶点激动剂注液和口服产品HRS9531，以及下一代肠促胰岛素产品HRS-4729。 恒瑞医药还将获得首付款和近期里程碑总计1.1亿美元，2亿美元临床及监管里程碑金额，累计不超过57.25亿美元销售里程碑金额，一定比例的销售分成，总金额达60.35亿美元。 [54]11.6亿美元：礼来×Aktis Oncology 5月21日，Aktis Oncology（下称“Aktis”）宣布与礼来达成多靶点发现合作协议。本次合作旨在利用Aktis专有的基于新型微型蛋白技术的放射性药物平台，与礼来在肿瘤药物开发和商业化方面的专业知识相结合，共同开发针对多种实体肿瘤的潜在“first-in-class”和差异化治疗方法。 根据协议条款，除了礼来公司对Aktis的股权投资外，Aktis还将获得6000万美元的合作预付款。此外，Aktis将有资格获得高达11亿美元的潜在临床前、临床、监管和商业里程碑，以及销售分成。相对应地，关于Aktis根据礼来选定的一系列靶点所发现的放射性药物治疗和诊断产品，礼来也将获得其在全球范围内的开发权利。 [55]12亿美元：武田×达歌生物 5月23日，达歌生物宣布与武田达成多靶点合作研发及独家许可协议，以发现和开发用于肿瘤学、神经科学和炎症领域多个靶点的新型分子胶降解剂。 本次合作的重点在于达歌生物的GlueXplorer平台。通过利用其该平台，达歌生物将针对武田选定的特定疾病靶点发现、验证和优化分子胶降解剂，并在达到一定进展阶段后，移交给武田进行进一步开发和商业化。 根据协议条款，达歌生物将获得首付款和潜在里程碑，最高可达12亿美元。同时，武田也会对达歌生物进行股权投资。 [56]18.25亿美元：BioNTech×宜联生物 5月27日，苏州宜联生物医药有限公司（下称“宜联生物”）宣布与BioNTech达成一项新的战略合作。通过本次合作，BioNTech将获得利用宜联生物的抗体偶联药物（ADC）技术平台TMALIN，开发针对指定前沿创新靶点ADC产品的独家选择权及相应全球独家许可。 值得注意的是，这是自去年10月份双方关于HER3 ADC授权合作后的再度合作。此次，宜联生物将有资格获得来自BioNtech的2500万美元预付款、18亿开发、监管和商业化里程碑付款，以及未来基于全球年度销售净额的销售分成。 [57]6.975亿美元：百时美施贵宝×Prothena Corporation 5月28日，Prothena Corporation（下称“Prothena”）宣布百时美施贵宝获得其PRX019的全球独家许可。宣布百时美施贵宝获得PRX019的全球独家许可。PRX019是一款用于治疗神经退行性疾病的潜在药物，具体靶点未公开，其IND申请已于2023年12月获FDA批准。Prothena计划在今年年底前启动PRX019的Ⅰ期临床试验。 根据协议条款，Prothena将有资格获得高达6.175亿美元的额外开发、监管和销售里程碑付款。此外，该司还将有资格获得净销售额的销售分成。 [58]2000万美元预付款：吉利德×Cartography Biosciences 5月28日，吉利德与Cartography Biosciences（下称“Cartography”）达成战略合作协议，共同为三阴性乳腺癌（TNBC）和最常见的非小细胞肺癌（NSCLC）腺癌患者发现和开发治疗方法。 这项为期多年的合作将利用Cartography的计算和基因组学平台，致力发现新的肿瘤选择性靶抗原和抗原对。吉利德可选择通过交易确定的几个目标，负责所选项目的进一步研究、开发和商业化。 根据协议条款，Cartography将获得2000万美元的预付款和更多的近期临床前里程碑。此外，该司还有资格获得未披露的开发、监管和商业里程碑金额和销售分成。 [59]3712.5万美元：三生制药旗下×翰宇药业 5月28日，三生制药发布公告，其子公司浙江三生蔓迪药业有限公司（下称“三生蔓迪”）与深圳翰宇药业股份有限公司（下称“翰宇药业”）签署《司美格鲁肽注射液合作协议》。双方将围绕该产品的药物开发、临床研究、注册申报、大健康渠道、以及品牌打造等环节进行协同合作。 本次合作模式包括交易对价、独家供应、以及后端分成。三生蔓迪将向翰宇药业支付最高人民币2.7亿元（3712.5万美元）里程碑付款，其中包含人民币4500万元（618.8万美元）的临床前技术成果对价款，此外，三生蔓迪还将向翰宇药业支付独家采购价以及一定比例的销售分成。   六月   [60]6.155亿美元：康宁杰瑞×ArriVent Biopharma 6月5日，康宁杰瑞发布公告，宣布与ArriVent Biopharma（下称“ArriVent”）达成合作协议。本次合作将利用康宁杰瑞专有的连接子载荷平台（Alphatecan）及糖基定点偶联平台，共同发现及开发创新ADC药物。 根据协议条款，康宁杰瑞将获得总计达6.155亿美元的预付款和潜在里程碑付款，以及一定比例的销售分成，并保留相关ADC产品在大中华区的开发及商业化权益。ArriVent则拥有相关ADC产品在海外肿瘤领域的独家开发和商业化权益。 [61]12亿美元：益普生×Marengo 6月8日，益普生和Marengo Therapeutics Inc宣布扩大其正在进行的肿瘤学研究合作。此次合作的重点在于Marengo的下一代精准T细胞接合器（TCE）技术TriSTAR。 靶向“冷”肿瘤的传统TCE由于患者体内T细胞质量差和耗竭，疗效有限。Marengo专有的“first-in-class”的 TriSTAR TCE有可能克服这些限制，将新的和扩展的高度激活的记忆Vβ T细胞库重定向到肿瘤。相关团队将专注于探索“冷”肿瘤的潜力，这些肿瘤在用TCEs治疗时通常无法触发强烈的免疫反应。 根据协议条款，益普生将负责开发候选提名后的所有活动。如果满足所有里程碑，Marengo将获得总额达12亿美元的预付款和潜在付款，以及销售分成。 [62]具体金额未披露：辉瑞×Flagship Pioneering 6月12日，Flagship Pioneering和其创建的新锐公司ProFound Therapeutics（下称“ProFound”）宣布与辉瑞达成基础研究合作协议，以发现潜在下一代“first-in-class”的减肥疗法。 ProFound公司基于对转译组的研究，构建了名为ProFoundry的图谱，这一数据库包含数以万计的新型蛋白质，包括它们的连接性、功能以及在健康和疾病中的作用。本次合作将利用ProFound专有的ProFoundry平台，与Flagship内部研发部Pioneering Medicines合作，从扩展的人类蛋白质组中识别潜在的新型蛋白质疗法，并评估其与治疗肥胖症的治疗相关性。在ProFound的早期验证活动之后，辉瑞将可以选择根据辉瑞和Flagship之间的战略合作伙伴关系条款推进选定的研究项目。 [63]17.1亿美元：艾伯维×明济生物 6月13日，明济生物制药（北京）有限公司和艾伯维宣布达成一项许可协议，共同推进推进FG-M701用于炎症性肠病（IBD）治疗的开发进程。 FG-M701是一种用于治疗炎症性肠病的下一代TL1A抗体，该靶点在炎症性肠病中已获得临床验证。与第一代TL1A抗体相比，FG-M701通过独特的工程化改造，旨在为炎症性肠病治疗提供更高的疗效并减少给药频率，具备成为同类最佳的潜力。目前正处于临床前开发阶段。此外，据明济生物介绍，其专有的基于结构的靶向进化平台（STEP）技术平台或将助力此次产品合作。 根据协议条款，艾伯维将获得FG-M701在全球进行开发、生产和商业化的独家许可权。明济生物将获得1.5亿美元的首付款和近期里程碑付款，并有资格获得后续高达15.6亿美元的临床开发、监管注册和商业化里程碑付款，以及一定比例的销售分成。 [64]13亿美元：武田×亚盛医药 6月14日，亚盛医药宣布与武田达成合作，就奥雷巴替尼（Olverembatinib）达成独家许可协议。这是一种口服、潜在“best-in-class”的第三代BCR-ABL酪氨酸激酶抑制剂（TKI），目前正在开发中，用于治疗慢性粒细胞白血病（CML）和其他血液系统癌症。 当前，该药物已在中国上市，用于治疗携带T315I突变的TKI耐药慢性期慢性粒细胞白血病（CP-CML）或加速期CML（AP-CML）成人患者，以及对第一代和第二代TKI耐药和/或不耐受的CP-CML成人患者。此外，奥雷巴替尼也已被FDA授予孤儿药资格认定和快速通道认定，并被EMA授予孤儿药认定。 根据协议条款，亚盛医药将于协议签署后收到1亿美元的选择权付款，并有资格获得最高约12亿美元的选择权行使费以及额外的潜在里程碑付款。此外，亚盛医药将从武田获得少数股权投资。一旦选择权被行使，武田将获得开发及商业化奥雷巴替尼的全球权利许可（除大中华区外）。在行使前，亚盛医药将全权负责奥雷巴替尼的所有临床开发事宜。 [65]18亿美元：罗氏×Ascidian Therapeutics 6月18日，Ascidian Therapeutics宣布与罗氏达成研究合作和许可协议，聚焦发现和开发靶向神经系统疾病的RNA外显子编辑疗法。 Ascidian的RNA外显子编辑平台旨在提高RNA药物的治疗可能性，并治疗当今基因编辑技术无法解决的疾病。该平台能够靶向大基因和具有高突变变异的基因，同时保持天然基因表达模式和水平。通过重写RNA，Ascidian的外显子编辑技术旨在提供基因治疗的持久性，同时大大降低与直接DNA编辑和基因替换相关的风险。 此次合作中，Ascidian将向罗氏提供针对未公开神经靶点的RNA外显子编辑技术的独家靶标特异性权利。Ascidian将与罗氏合作开展发现和某些临床前活动，罗氏将负责某些临床前活动，以及进一步的临床开发、制造和商业化。 根据协议条款，Ascidian将获得4200万美元的首期付款，并有资格获得高达18亿美元的研究、临床和商业里程碑付款，以及全球商业销售的销售分成。Ascidian可自由地在内部或与其他合作者一起开发针对其他神经靶点的程序。 [66]12.07亿美元：Day One Biopharmaceuticals×MabCare Therapeutics 6月18日，Day One Biopharmaceuticals宣布已与MabCare Therapeutics公司达成独家许可协议，获得靶向蛋白酪氨酸激酶7（PTK7）的创新ADC药物MTX-13的全球独家开发、生产和商业化权利（除大中华区外）。 4月，MTX-13的IND申请已获FDA批准，并更名为“DAY301”。在临床前研究中，DAY301显示出对多种实体瘤的抗肿瘤活性。该药物靶向的PTK7是一种高度保守的催化失活的跨膜蛋白，在多种成人癌症（包括食道癌、卵巢癌、肺癌和子宫内膜癌）以及儿童癌症（如神经母细胞瘤、横纹肌肉瘤和骨肉瘤）中高度表达。PTK7在正常组织或器官中的表达有限，使其成为ADC疗法开发的理想靶点。 根据协议条款，MabCare将获得5500万美元的预付款，并有资格获得额外高达11.52亿美元的开发、监管和商业化里程碑付款。 [67]7.4亿美元：赛诺菲×Belharra Therapeutics 6月18日，Belharra Therapeutics（下称“Belharra”）宣布与赛诺菲达成战略合作，共同推进创新小分子免疫疾病治疗药物的发现。 本次合作将利用Belharra的专有非共价化学蛋白质组学平台，对赛诺菲指定的免疫学靶点进行筛选和验证。该平台旨在提供广泛和无偏倚的化学蛋白质组学筛选能力，利用一组计算设计的非共价类药物分子库，通过光亲化学（photoaffinity chemistry）来识别与特定分子结合的蛋白质以及靶蛋白上的精确结合位置，能够揭示任何细胞类型中任何蛋白质的结合口袋，为候选药物提供了一条更有效的发展路径。 根据条款协议，Belharra有资格获得4000万美元的预付款和近期里程碑付款、高达近7亿美元的研究、开发和商业里程碑付款，以及净销售额的销售分成。 [68] 11.4亿美元：礼来xRadionetics Oncologye 6月30日，Radionetics Oncology(下称“Radionetics”)宣布与礼来建立战略合作关系，以推进其专有的GPCR靶向小分子放射性药物。 根据协议条款，Radionetics将收到1.4亿美元的预付款，在行权期结束后，礼来拥有未来以10亿美元价格收购Radionetics的独家选择权。在行权期内，Radionetics将继续构建靶向性放射性疗法管线，包括使用Radionetics专有发现平台开发GPCR靶向小分子放射性配体治疗药物。  主要参考文献  [1]Voyager官网：https://ir.voyagertherapeutics.com/news-releases/news-release-details/voyager-therapeutics-enters-capsid-license-agreement-and [2]罗氏官网：https://www.roche.com.cn/media/releases/02-01-2024 [3]BI 中文官网：https://www.boehringer-ingelheim.cn/press-release/bo-lin-ge-yin-ge-han-xie-shou-rui-bo-sheng-wu-gong-tong-kai-fa-zhi-liao-gan-bing-de-xiao-he-suan-chuang-xin-liao-fa [4]Remix Therapeutics官网： Remix Therapeutics™ Enters Collaboration with Roche for the Discovery and Development of Small Molecule Therapeutics Modulating RNA Processing [7]Avenzo官网：https://avenzotx.com/press-releases/avenzo-therapeutics-announces-global-license-of-avzo-021-arts-021-a-potentially-best-in-class-clinical-stage-cdk2-inhibitor-from-allorion-therapeutics/ [10][11]Isomorphic Labs官网：https://www.isomorphiclabs.com/articles/isomorphic-labs-kicks-off-2024-with-two-pharmaceutical-collaborations [12]Simchatx官网: https://simchatx.com/simcha-therapeutics-announces-license-option-agreement-to-develop-novel-decoy-resistant-il-18-for-use-in-cell-therapy-applications/ [13]Genevant官网：https://www.genevant.com/genevant-sciences-to-collaborate-with-tome-biosciences-to-develop-gene-editing-therapeutic-for-rare-liver-disorder/ [16]EraCal官网： https://www.eracal.ch/_files/ugd/b8426d_f96f5439a98b4f2db3e0fa5f5ee1c570.pdf [17]康宁杰瑞官网：https://www.alphamabonc.com/html/news/2648.html [18]BioNTech官网： https://investors.biontech.de/news-releases/news-release-details/biontech-and-autolus-announce-strategic-car-t-cell-therapy [19]Astellas官网：https://newsroom.astellas.us/2024-02-15-Astellas-and-Kelonia-Therapeutics-Enter-into-Research-and-License-Agreement-to-Develop-Novel-Immuno-Oncology-Therapeutics [20]Abbvie官网：https://news.abbvie.com/2024-02-22-AbbVie-and-Tentarix-Announce-Collaboration-to-Develop-Conditionally-Active,-Multi-Specific-Biologics-for-Oncology-and-Immunology [21]Immunocore官网： https://www.immunocore.com/investors/news/press-releases/detail/83/immunocore-announces-clinical-trial-collaboration-and-supply-agreement-with-bristol-myers-squibb-to-evaluate-imc-f106c-prame-hla-a02-in-combination-with-nivolumab-in-its-registrational-phase-3-first-line-advanced-cutaneous-melanoma-trial [22]Neomorph官网：https://neomorph.com/index.html#news [23]Abbvie官网： https://news.abbvie.com/2024-02-28-AbbVie-and-OSE-Immunotherapeutics-Announce-Partnership-to-Develop-a-Novel-Monoclonal-Antibody-for-the-Treatment-of-Chronic-Inflammation [24]Viatris官网： https://investor.viatris.com/news-releases/news-release-details/viatris-and-idorsia-enter-significant-global-research-and [25]C4T官网： https://ir.c4therapeutics.com/news-releases/news-release-details/c4-therapeutics-announces-strategic-discovery-research [26]BridgeBio Pharma官网： https://investor.bridgebio.com/news-releases/news-release-details/bridgebio-pharma-and-bayer-announce-european-licensing-agreement [27]吉利得官网： https://www.gilead.com/news-and-press/press-room/press-releases/2024/3/gilead-and-merus-announce-collaboration-to-discover-novel-antibody-based-trispecific-t-cell-engagers [28]BI官网： Boehringer Ingelheim and Sosei Heptares join forces to develop first-in-class treatments targeting all symptoms of schizophrenia https://www.boehringer-ingelheim.com/science-innovation/human-health-innovation/new-partnership-develop-schizophrenia-treatments [29]Pearl Bio官网（指向businesswire的报道） Pearl Bio Inks Collaboration with Merck to Discover Novel Engineered Biologics https://www.businesswire.com/news/home/20240312580796/en/Pearl-Bio-Inks-Collaboration-with-Merck-to-Discover-Novel-Engineered-Biologics [30]Allogene官网： Allogene Therapeutics and Arbor Biotechnologies Announce Global Gene Editing Licensing Agreement to Support Advancement of Next-Generation Allogeneic CAR T Platform in Autoimmune Disease https://ir.allogene.com/news-releases/news-release-details/allogene-therapeutics-and-arbor-biotechnologies-announce-global [31]BI中文官网： 勃林格殷格翰与上海莱士达成重磅合作，携手开发血友病创新药物 https://boehringer-ingelheim.cn/hezuo/bolingeyingehanyushanghailaishidachengzhongbanghezuoxieshoukaifaxueyoubingchuangxinyaowu [32]Parvus官网： Parvus Announces Collaboration with AbbVie to Develop IBD Therapies Based on the Parvus Navacim Platform Technology https://parvustx.com/parvus-announces-collaboration-with-abbvie-to-develop-ibd-therapies-based-on-the-parvus-navacim-platform-technology/ [33]Gilead官网： Gilead and Xilio Announce Exclusive License Agreement for Tumor-Activated IL-12 Program https://www.gilead.com/news-and-press/press-room/press-releases/2024/3/gilead-and-xilio-announce-exclusive-license-agreement-for-tumor-activated-il-12-program [34]康哲药业官网： https://web.cms.net.cn/zh/2024/04/%e5%ba%b7%e5%93%b2%e8%8d%af%e4%b8%9a%e4%b8%8eincyte%e5%ae%a3%e5%b8%83%e5%b0%b1%e5%8f%a3%e6%9c%8djak1%e6%8a%91%e5%88%b6%e5%89%82povorcitinib%e5%9c%a8%e4%b8%ad%e5%9b%bd%e5%a4%a7%e9%99%86%e3%80%81/ [35]Ipsen官网 Ipsen and Sutro Biopharma announce exclusive global licensing agreement for an ADC targeting solid tumors https://www.ipsen.com/press-releases/ipsen-and-sutro-biopharma-announce-exclusive-global-licensing-agreement-for-an-adc-targeting-solid-tumors/ [36]中国生物制药官网： 重磅官宣 | 中国生物制药与勃林格殷格翰达成战略合作 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https://www.prnewswire.com/news-releases/kumquat-biosciences-and-takeda-enter-into-strategic-collaboration-and-exclusive-global-license-agreement-to-advance-novel-oral-immuno-oncology-drug-candidate-302117294.html [41]skyhawk官网： https://www.skyhawktx.com/post/ipsen-and-skyhawk-therapeutics-announce-rna-targeting-research-collaboration-in-rare-neurological-di [42]BI官网： https://www.boehringer-ingelheim.cn/hezuo/bolingeyingehanjiasukaifawanqiganbingxinxingzaishengliaofa [43]再生元官网： https://investor.regeneron.com/news-releases/news-release-details/regeneron-and-mammoth-biosciences-collaborate-pursue-next [44]PR Newswire新闻网站文章（转自圣诺医药）：https://www.prnasia.com/story/444889-1.shtml [45]repertoire官网： https://www.repertoire.com/about/press-releases/repertoire-immune-medicines-and-bristol-myers-squibb-announce-multi-year-strategic-collaboration-to-develop-tolerizing-vaccines-for-autoimmune-diseases [46]官网新闻： https://contents.xj-storage.jp/xcontents/45870/ede8afc6/82e1/421c/840a/ec42a545e6b7/20240430080349842s.pdf [47]Chiesi官网： https://www.chiesi.com/en/gossamer-bio-collaboration-pulmonary-arterial-hypertension/ [48]Flagship pioneering官网： https://www.flagshippioneering.com/news/press-release/flagship-pioneering-and-metaphore-biotechnologies-announce-research-collaboration-with-novo-nordisk-to-develop-next-generation-therapeutics-for-obesity-management [49]https://www.shionogi.com/global/en/news/2024/05/e20240510.html [50]https://ir.fulcrumtx.com/news-releases/news-release-details/fulcrum-therapeutics-enters-collaboration-and-license-agreement [51]艾伯维官网： https://news.abbvie.com/2024-05-13-AbbVie-and-Gilgamesh-Pharmaceuticals-Announce-Collaboration-and-Option-to-License-Agreement-to-Develop-Next-Generation-Therapies-for-Psychiatric-Disorders [52]Takeda官网： https://www.takeda.com/newsroom/newsreleases/2024/ac-immune-and-takeda-sign-exclusive-option-and-license-agreement-for-active-immunotherapy-targeting-amyloid-beta-for-alzheimers-disease/ [53]江苏恒瑞医药有限公司关于签署授权许可协议暨对外投资的公告 [54]https://www.aktisoncology.com/news/aktis-oncology-enters-into-strategic-collaboration-with-lilly-to-discover-and-develop-novel-anticancer-radiopharmaceuticals/ [57]Prothena官网： https://ir.prothena.com/investors/press-releases/news-details/2024/Prothena-Announces-Bristol-Myers-Squibb-Opt-in-for-Exclusive-Global-License-for-PRX019-the-Second-Program-from-Global-Neuroscience-Research-and-Development-Collaboration/default.aspx [60]arrivent官网： https://ir.arrivent.com/news-releases/news-release-details/arrivent-announces-multi-target-adc-collaboration-alphamab [61]ipsen官网： https://www.ipsen.com/press-releases/ipsen-and-marengo-therapeutics-announce-second-strategic-partnership-to-advance-precision-t-cell-engagers-from-marengos-tri-star-platform/ [62]flagship pioneering官网： https://www.flagshippioneering.com/news/press-release/flagship-pioneering-and-profound-therapeutics-announce-agreement-to-identify-novel-first-in-class-therapeutics-for-the-treatment-of-obesity-under-strategic-partnership-with-pfizer [63]Abbvie官网： https://news.abbvie.com/2024-06-13-AbbVie-and-FutureGen-Announce-License-Agreement-to-Develop-Next-Generation-Therapy-for-Inflammatory-Bowel-Disease [65] https://www.prnewswire.com/news-releases/ascidian-therapeutics-enters-collaboration-with-roche-for-discovery-and-development-of-rna-exon-editing-therapeutics-targeting-neurological-diseases-302174743.html [66]dayonebio官网： https://ir.dayonebio.com/news-releases/news-release-details/day-one-expands-pipeline-potential-first-class-clinical-stage [67]belharra官网： https://belharratx.com/press-releases/belharra-therapeutics-announces-strategic-collaboration-with-sanofi-to-advance-discovery-of-novel-small-molecule-therapeutics-for-immunological-diseases/ 共建Biomedical创新生态圈！ 如何加入BiG会员？