A Phase II, Open-label, Multicentre, Single-arm Study of Durvalumab Plus Oleclumab in Patients With Locally Advanced, Unresectable Non-small Cell Lung Cancer Who Have Not Progressed Following Definitive, Platinum-Based Chemoradiation Therapy (LADOGA)

The purpose of this Phase II, open-label, multicentre, single-arm study is to assess efficacy and safety of durvalumab (MEDI4736) in combination with oleclumab (MEDI9447) in participants with locally advanced (Stage III), unresectable non-small cell lung cancer (NSCLC), who have not progressed following platinum-based concurrent or sequential chemoradiotherapy (cCRT or sCRT).

Start Date24 Sep 2024

Sponsor / Collaborator

AstraZeneca PLC

NCT06060405 / RecruitingPhase 2IIT

Durvalumab and Oleclumab in Resectable PDAC: A Window of Opportunity Study (DORA Trial)

This is a multi-site Canadian, window of opportunity study to evaluate the immune activity of durvalumab and oleclumab in resectable pancreatic ductal adenocarcinoma (PDAC) when given prior to surgery.

Start Date29 Nov 2023

Sponsor / Collaborator

University Health Network

CTR20221538 / Active, not recruitingPhase 3

一项评价度伐利尤单抗 + Oleclumab和度伐利尤单抗 + Monalizumab用于根治性含铂药物同步放化疗后未进展的局部晚期（III期）、不可切除非小细胞肺癌（NSCLC）患者的双盲、安慰剂对照、随机、多中心、国际、III期研究（PACIFIC-9）

[Translation] A double-blind, placebo-controlled, randomized, multicenter, international, phase III study evaluating durvalumab plus oleclumab versus durvalumab plus monalizumab in patients with locally advanced (stage III), unresectable non-small cell lung cancer (NSCLC) who have not progressed after definitive platinum-based concurrent chemoradiotherapy (PACIFIC-9)

主要目的旨在为证明在既往含铂cCRT治疗后未发生疾病进展的不可切除III期NSCLC受试者中度伐利尤单抗 + Oleclumab优效于度伐利尤单抗 + 安慰剂; 以及证明在既往含铂cCRT治疗后未发生疾病进展的不可切除III期NSCLC受试者中度伐利尤单抗 + Monalizumab优效于度伐利尤单抗 + 安慰剂。

[Translation]

The primary objectives are to demonstrate the superiority of durvalumab + oleclumab over durvalumab + placebo in subjects with unresectable stage III NSCLC who have not had disease progression after prior platinum-based cCRT; and to demonstrate the superiority of durvalumab + monalizumab over durvalumab + placebo in subjects with unresectable stage III NSCLC who have not had disease progression after prior platinum-based cCRT.

Start Date15 Aug 2022

Sponsor / Collaborator

AstraZeneca Global R&D (China) Co., Ltd.

[+2]

100 Clinical Results associated with Oleclumab

100 Translational Medicine associated with Oleclumab

100 Patents (Medical) associated with Oleclumab

Literatures (Medical) associated with Oleclumab

31 Dec 2024·Cancer Biology & Therapy

Efficacy and pharmacodynamic effect of anti-CD73 and anti-PD-L1 monoclonal antibodies in combination with cytotoxic therapy: observations from mouse tumor models

Article

Author: Hair, James ; Lapointe, Jean-Martin ; Galvani, Elena ; Hammond, Scott A ; Eyles, Jim ; Brown, Lee ; Watkins, Amanda ; Kumar, Rakesh ; Kaistha, Brajesh P ; Kar, Gozde ; Garcon, Fabien ; Slidel, Tim ; Anderton, Judith ; Dannhorn, Andreas ; Ryan, Kelli ; Hardaker, Elizabeth ; Opoku-Ansah, Grace ; Ilieva, Kristina ; Luheshi, Nadia ; Mullins, Stefanie ; Wilkinson, Robert W ; Dovedi, Simon

CD73 is a cell surface 5'nucleotidase (NT5E) and key node in the catabolic process generating immunosuppressive adenosine in cancer. Using a murine monoclonal antibody surrogate of Oleclumab, we investigated the effect of CD73 inhibition in concert with cytotoxic therapies (chemotherapies as well as fractionated radiotherapy) and PD-L1 blockade. Our results highlight improved survival in syngeneic tumor models of colorectal cancer (CT26 and MC38) and sarcoma (MCA205). This therapeutic outcome was in part driven by cytotoxic CD8 T-cells, as evidenced by the detrimental effect of CD8 depleting antibody treatment of MCA205 tumor bearing mice treated with anti-CD73, anti-PD-L1 and 5-Fluorouracil+Oxaliplatin (5FU+OHP). We hypothesize that the improved responses are tumor microenvironment (TME)-driven, as suggested by the lack of anti-CD73 enhanced cytopathic effects mediated by 5FU+OHP on cell lines in vitro. Pharmacodynamic analysis, using imaging mass cytometry and RNA-sequencing, revealed noteworthy changes in specific cell populations like cytotoxic T cells, B cells and NK cells in the CT26 TME. Transcriptomic analysis highlighted treatment-related modulation of gene profiles associated with an immune response, NK and T-cell activation, T cell receptor signaling and interferon (types 1 & 2) pathways. Inclusion of comparator groups representing the various components of the combination allowed deconvolution of contribution of the individual therapeutic elements; highlighting specific effects mediated by the anti-CD73 antibody with respect to immune-cell representation, chemotaxis and myeloid biology. These pre-clinical data reflect complementarity of adenosine blockade with cytotoxic therapy, and T-cell checkpoint inhibition, and provides new mechanistic insights in support of combination therapy.

31 Dec 2024·OncoImmunology

Short-term cultured tumor fragments to study immunotherapy combinations based on CD137 (4-1BB) agonism

Article

Author: Bolaños, Elixabet ; Sanmamed, Miguel F ; Rodríguez, Inmaculada ; Melero, Ignacio ; Fernández de Piérola, Eva ; Mínguez, José Ángel ; Herrero-Martin, Claudia ; Chacón, Enrique ; Diez-Caballero, Fernando ; Gomis, Gabriel ; Chiva, Santiago ; Azpilikueta, Arantza ; de Andrea, Carlos ; Teijeira, Álvaro ; Sánchez-Gregorio, Sandra ; Eguren-Santamaría, Iñaki ; Molero-Glez, Paula

Biomarkers for cancer immunotherapy are an unmet medical need. The group of Daniela Thommen at the NKI recently reported on novel methodologies based on short-term cultures of patient-derived tumor fragments whose cytokine concentrations in the supernatants and activation markers on infiltrating T cells were associated with clinical response to PD-1 blockade. We set up a similar culture technology with tumor-derived fragments using mouse tumors transplanted into syngeneic immunocompetent mice to test an agonist anti-CD137 mAb and its combinations with anti-PD-1 and/or anti-TGF-β. Increases in IFNγ concentrations in the tissue culture supernatants were detected upon in-culture activation with the anti-CD137 and anti-PD-1 mAb combinations or concanavalin A as a positive control. No other cytokine from a wide array was informative of stimulation with these mAbs. Interestingly, increases in Ki67 and other activation markers were substantiated in lymphocytes from cell suspensions gathered at the end of 72 h cultures. In mice bearing bilateral tumors in which one was excised prior to in vivo anti-CD137 + anti-PD-1 treatment to perform the fragment culture evaluation, no association was found between IFNγ production from the fragments and the in vivo therapeutic outcome in the non-resected contralateral tumors. The experimental system permitted freezing and thawing of the fragments with similar functional outcomes. Using a series of patient-derived tumor fragments from excised solid malignancies, we showed IFNγ production in a fraction of the studied cases, that was conserved in frozen/thawed fragments. The small tumor fragment culture technique seems suitable to preclinically explore immunotherapy combinations.

13 Sep 2024·Future Oncology

PACIFIC-9: Phase III trial of durvalumab + oleclumab or monalizumab in unresectable stage III non-small-cell lung cancer

Article

Author: Barlesi, Fabrice ; Mann, Helen ; Newton, Michael ; Zimmer Gelatti, Ana Caroline ; Goldberg, Sarah B ; Cho, Byoung Chul ; Yoh, Kiyotaka ; Gopinathan, Aarthi ; Bielecka, Zofia Felicja ; Aggarwal, Charu

Evidence from the Phase III PACIFIC trial established durvalumab, a monoclonal antibody (mAb) targeting PD-L1, following concurrent chemoradiotherapy (cCRT) as a global standard of care for patients with unresectable, stage III non-small-cell lung cancer (NSCLC). There remains an unmet need to improve upon the outcomes achieved with the PACIFIC regimen. Combining durvalumab with other immunotherapies may improve outcomes further. Two such immunotherapies include oleclumab, an mAb targeting CD73, and monalizumab, an mAb targeting NKG2A. Both agents demonstrated antitumor activity in early-phase trials. PACIFIC-9 (NCT05221840) is an international, double-blind, randomized, placebo-controlled, Phase III trial comparing durvalumab plus either oleclumab or monalizumab with durvalumab plus placebo in patients with unresectable, stage III NSCLC and no disease progression following cCRT.Clinical Trial Registration: NCT05221840 (ClinicalTrials.gov).

News (Medical) associated with Oleclumab

12 Sep 2024

·www.innate-pharma.com

Innate Pharma reports First Half 2024 Business Update and Financial Results | Innate Pharma

Positive results with lacutamab from TELLOMAK Phase 2 study in mycosis fungoides presented at ASCO 2024 NK-Cell engager SAR443579/IPH61011 first-in-human study advanced to Phase 2 and initiation of front-line AML Phase 1/2 combination studyUpdated data from dose-escalation part presented at EHA 2024 confirm clinical benefit and durable responses in patients with R/R AML IPH45, proprietary anti Nectin-4 ADC progressing towards Phase 1 in H2 2024 Monalizumab data from AstraZeneca-sponsored Phase 2 study in early NSCLC presented at WCLC Cash position of €102.1 million2 as of June 30, 2024, anticipated cash runway to end of 2025 Conference call to be held today at 2:00 p.m. CEST / 8:00 a.m. EDT Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) (“Innate” or the “Company”) today reported its consolidated financial results for the six months ended June 30, 2024. The consolidated financial statements are attached to this press release. “We are focused on our growth strategy as we advance our pipeline,” said Hervé Brailly, Chief Executive Officer ad interim of Innate Pharma. “We recently presented Phase 2 results with lacutamab in mycosis fungoides at ASCO and are engaged in discussions with the FDA on next steps in its development. We are also progressing towards Phase 1 for our first and differentiated ADC program IPH45, targeting Nectin-4.” ***** Access to live webcast: https://events.q4inc.com/attendee/127231232 Participants may also join via telephone by registering in advance of the event at https://registrations.events/direct/Q4I953384196 This information can also be found on the Investors section of the Innate Pharma website, www.innate-pharma.com. A replay of the webcast will be available on the Company website for 90 days following the event. ***** 1 Developed by Sanofi 2 Including short term investments (€21.8 million) and non-current financial instruments (€10.3 million) TELLOMAK is a global, open-label, multi-cohort Phase 2 clinical trial evaluating lacutamab in patients with Sézary syndrome and mycosis fungoides. Favorable results from the Phase 2 TELLOMAK study with lacutamab in mycosis fungoides were presented at the American Society of Clinical Oncology (ASCO) 2024 Annual Meeting in June 2024. The data demonstrate that treatment with lacutamab resulted in meaningful antitumor activity, regardless of the KIR3DL2 baseline expression, and an overall favorable safety profile. The global objective response rate was 16.8% (Olsen 2011) and 22.4% (Olsen 2022), including 2 complete responses and 16 partial responses. The Phase 2 KILT (anti-KIR in T Cell Lymphoma) trial, an investigator-sponsored, randomized controlled trial led by the Lymphoma Study Association (LYSA) to evaluate lacutamab in combination with chemotherapy GEMOX (gemcitabine in combination with oxaliplatin) versus GEMOX alone in patients with KIR3DL2-expressing relapsed/refractory PTCL is ongoing and continues to recruit patients. ANKET® is Innate’s proprietary platform for developing next-generation, multi-specific NK cell engagers to treat certain types of cancer. Innate’s pipeline includes five public drug candidates born from the ANKET® platform: SAR443579/IPH6101 (SAR’579; trifunctional anti-CD123 NKp46-CD16 NKCE), SAR445514/IPH6401 (SAR’514 trifunctional anti-BCMA NKp46-CD16 NKCE), IPH62 (anti-B7-H3), IPH67 (target undisclosed, solid tumors) and tetra-specific IPH6501 (anti-CD20 with IL-2v). Several other undisclosed proprietary preclinical targets are being explored. IPH6501 is Innate’s proprietary CD20-targeted IL-2v bearing second-generation ANKET®. In March 2024 the first patient was dosed in the Phase 1/2 clinical trial evaluating IPH6501 in B cell Non-Hodgkin’s lymphoma (B-NHL). The study is planned to enroll up to 184 patients. Innate presented preclinical data of IPH6501 at the ASCO Annual Meeting and European Hematology Association (EHA) Annual congress in June 2024. Preclinical data showed that IPH6501 depletes autologous CD20+ B cells from healthy donors with greater efficacy and lower induction of pro-inflammatory cytokines than a CD20-T-cell engager. IPH6501 also effectively and preferentially stimulates NK cell proliferation from peripheral blood mononuclear cells of R/R NHL patients. The trial-in-progress of the Phase 1/2 study has been presented at the European Hematology Association (EHA) and ASCO in 2024. The Phase 1/2 clinical trial by Sanofi is progressing well, evaluating SAR’579 / IPH6101, a trifunctional anti-CD123 NKp46-CD16 NK-cell engager and ANKET® platform lead asset, in patients with relapsed or refractory acute myeloid leukemia (AML), B-cell acute lymphoblastic leukemia (B-ALL) or high-risk myelodysplastic syndrome (HR-MDS). Updated efficacy and safety results from the dose-escalation part of the Phase 1/2 study with SAR'579 / IPH6101, were shared in an oral presentation at the EHA 2024 Congress. The data demonstrated that SAR’579 continues to show clinical benefit and durable responses along with a favorable safety profile in patients with R/R AML, with 5 complete remissions (4 CR / 1 CRi) achieved at 1 mg/kg, with durable CR (>10 months) observed in 3 patients. In April 2024, Sanofi advanced SAR’579 / IPH6101, to the Phase 2 preliminary dose expansion of the trial. Under the terms of the 2016 research collaboration with Sanofi, the progression to the dose expansion part of the trial has triggered a milestone payment from Sanofi to Innate of €4m. In July 2024, Sanofi initiated a new Phase 1 / Phase 2, randomized, open label, multi-cohort, multi-center study (NCT06508489) assessing the safety, tolerability and preliminary efficacy of SAR’579 / IPH6101 administered in combination with azacitidine and venetoclax in patients with CD123 expressing hematological malignancies in newly diagnosed AML. The Sanofi led Phase 1/2 clinical trial with SAR’514 / IPH6401, a trifunctional anti-BCMA Nkp46-CD16 NK-cell engager, in patients with Relapsed/Refractory Multiple Myeloma and Relapsed/Refractory Light-chain Amyloidosis is ongoing. IPH62 is a NK-cell engager program targeting B7-H3 from Innate’s ANKET® platform under development. Following a research collaboration period and upon candidate selection, Sanofi will be responsible for all development, manufacturing and commercialization. IPH67 is a NK-cell engager program in solid tumors from Innate’s ANKET® platform under development. Following a research collaboration period and upon candidate selection, Sanofi will be responsible for all development, manufacturing and commercialization. Sanofi still retains the option of one additional ANKET® target under the terms of the 2022 research collaboration and license agreement. Innate develops different approaches for the treatment of cancer utilizing its antibody engineering capabilities to deliver novel assets, with its innovative ANKET® platform and is also exploring Antibody Drug Conjugates (ADC) formats. IPH45 is Innate’s proprietary and differentiated exatecan-antibody drug conjugate (ADC) targeting Nectin-4. First preclinical data were presented in an oral presentation at the American Association for Cancer Research (AACR) Annual Meeting 2024. In preclinical studies, IPH45 shows anti-tumor efficacy in vivo, in Nectin-4 expressing tumors including in enfortumab vedotin (EV) refractory models. Importantly, IPH45 shows stronger activity than EV, in multiple urothelial carcinoma patient-derived xenografted (PDX) mice models, across Nectin-4 high and Nectin-4 low expression levels. In addition, IPH45 has anti-tumor activity in combination with anti-PD1 treatment in PD-1 resistant model in vivo and has a favorable safety profile in relevant animal toxicology models. IPH45 continues towards a Phase 1 trial in 2024. The Phase 3 PACIFIC-9 trial run by AstraZeneca evaluating durvalumab (anti-PD-L1) in combination with monalizumab or AstraZeneca’s oleclumab (anti-CD73) in patients with unresectable, Stage III non-small cell lung cancer (NSCLC) who have not progressed following definitive platinum-based concurrent chemoradiation therapy (CRT) is ongoing.After the period, the Independent Data Monitoring Committee recommended the continuation of the Phase 3 PACIFIC-9 trial based on a pre-planned analysis. Updated results from COAST, a Phase 2 study of durvalumab with oleclumab or monalizumab in patients with Stage III unresectable non-small-cell lung cancer were presented at the ASCO 2024 Annual Meeting, in June 2024. In this analysis of updated results from COAST, the combination of durvalumab plus oleclumab or monalizumab increased objective response rate, prolonged progression free survival, and trended toward improved overall survival compared to durvalumab alone. AstraZeneca presented interim results from the randomized NeoCOAST-2 Phase 2 platform trial during the 2024 World Conference on Lung Cancer in September 2024. In this preliminary analysis on the first 60 of 72 patients randomized to Arm 2, monalizumab added to durvalumab plus platinum-based chemotherapy doublet induced a pathological complete response rate of 26.7% [95% CI; 16.1–39.7] and a major pathological response rate of 53.3% [95% CI; 40.0–66.3] which are numerically higher than the durvalumab plus platinum doublet approved regimen. Treatment in Arm 2 showed manageable safety profile and no impact on surgical rate. The NeoCOAST-2 platform study is intended to assess the safety and efficacy of neoadjuvant durvalumab alone or combined with novel immuno-oncology agents and chemotherapy in resectable, early-stage NSCLC, followed by adjuvant treatment with durvalumab with or without the novel agents. The MATISSE Phase 2 clinical trial conducted by Innate in neoadjuvant lung cancer for IPH5201, an anti-CD39 blocking monoclonal antibody developed in collaboration with AstraZeneca, is ongoing and recruitment is on track. Following a pre-planned interim analysis after the period, the MATISSE Phase 2 trial continues according to plans. The investigator-sponsored CHANCES Phase 1 trial of IPH5301 with Institut Paoli-Calmettes is ongoing. Preliminary results will be presented at the upcoming (European Society of Medical Oncology) ESMO Annual Meeting 2024. The abstract, available on the ESMO website, states that IPH5301 was safe and well-tolerated with preliminary signals of monotherapy antitumor activity. In connection with Innate’s previous announcement that it had established an at-the-market (“ATM”) program, on January 16, 2024 Innate filed a new Registration Statement on Form F-3 (Registration No. 333-276164). On February 6, 2024, Innate filed a prospectus supplement relating to its previously established ATM program, pursuant to which it may, from time to time, offer and sell to eligible investors a total gross amount of up to $75 million of American Depositary Shares (“ADS”). Each ADS represents one ordinary share of Innate. As of June 30, 2024, no sales have been made under the program. Takeda made a strategic decision to terminate the license agreement executed in March 2023 for use of selected Innate antibodies in antibody drug-conjugates. Innate will regain full rights to these antibodies in Q4 2024. The key elements of Innate’s financial position and financial results as of and for the six-month period ended June 30, 2024 are as follows: Cash, cash equivalents, short-term investments and financial assets amounting to €102.1 million (€m) as of June 30, 2024 (€102.3m as of December 31, 2023). Revenue and other income amounted to €12.3m in the first half of 2024 (€40.2m in the first half of 2023) and mainly comprised of:Revenue from collaboration and licensing agreements, which mainly resulted from the partial or entire recognition of the proceeds received pursuant to the agreements with AstraZeneca, Sanofi and Takeda. They result from the partial or entire recognition of the proceeds received pursuant to such agreements. They are recognized when the entity's performance obligation is met. They are recognized at a point in time or spread over time according to the percentage of completion of the work that the Company is committed to carry out under these agreements:(i) Revenue from collaboration and licensing agreements for monalizumab decreased by €6.5m to €3.0m in the first half of 2024 (€9.5m in the first half of 2023). This change is mainly due to the recognition of increased revenue in the first six months of 2023. Indeed, as of June 30, 2023, the Company had analyzed the cost base used to calculate the percentage of completion of Phase 1/2 trials in connection with their progress. This analysis led to a reduction in the cost base through a re-estimation of projected expenses. As a result, this adjustment on the cost base had a positive impact on the percentage of completion and led to the recognition of additional revenue of €5.9 million for the first half of 2023 which was not replicated in 2024. (ii) Revenue related to the license and collaboration agreement signed with Sanofi in 2016 increased by €2.0m, to €4.0m for the six months ended June 30, 2024, as compared to €2.0m for the six months ended June 30, 2023. On April 15, 2024, the Company announced the treatment of the first patient in the Phase 2 dose expansion part of the Sanofi-sponsored clinical trial evaluating NK Cell Engager SAR443579/ IPH6101 in various blood cancers. Under the terms of the 2016 agreement, this trial progress triggered a milestone payment of €4.0 million fully recognized in revenue during the first quarter of 2024. This amount was received by the Company on May 17, 2024.As a reminder, the Company announced that, in June 2023, the first patient was dosed in a Sanofi-sponsored Phase 1/2 clinical trial evaluating IPH6401/SAR'514 in relapsed or refractory Multiple Myeloma. As provided by the licensing agreement signed in 2016, Sanofi made a milestone payment of €2.0 million, fully recognized in revenue as of June 30, 2023. This amount was received by the Company on July 21, 2023. (iii) Revenue related to the research collaboration and licensing agreement signed with Sanofi in 2022 decreased by €18.3m, to €0.4m for the six months ended June 30, 2024, as compared to €18.7m for the six months ended June 30, 2023. As previously announced, on January 25, 2023, the Company announced the expiration of the waiting period under the Hart-Scott-Rodino (HSR) Antitrust Improvements Act of 1976 and the effectiveness of the licensing agreement as of January 24, 2023. Consequently, the Company received an upfront payment of €25.0 million in March 2023, including €18.5 million for the exclusive license, €1.5 million for the research activities and €5.0 million for the option on two additional targets. The €18.5 million upfront payment relating to the exclusive license was fully recognized in revenue as of June 30, 2023. The €1.5 million upfront payment is recognized on a straight-line basis over the duration of the research activities that the Company has agreed to carry out. As a result, a €0.2 million has been recognized in revenue as of June 30, 2024 and June 30, 2023. Then, on December 19, 2023, the Company announced that Sanofi had exercised an option for one of the two targets. As a consequence, the Company recognized related income of €2.5 million as of December 31, 2023. This option exercise also resulted in a milestone payment of €15.0 million, including €13.3 million in respect of the exclusive license, which was fully recognized in income as of December 31, 2023, and €1.7 million in respect of research activities to be carried out by the Company, which will be recognized in income on a straight-line basis over the duration of the research activities that the Company has agreed to carry out. Sanofi and Innate will collaborate and work on the research activities defined in the contractual research program. These activities began during the first half of 2024. An amount of €0.2 million has been recognized in revenue as of June 30, 2024. Amounts not recognized in revenue are classified as deferred revenue. (iv) Revenues under the license agreement signed with Takeda in 2023 are nil for the first half of 2024, compared to €4.6 million for the first half of 2023. On April 3, 2023, the Company announced that it has entered into an exclusive license agreement with Takeda under which Innate grants Takeda exclusive worldwide rights to research and develop antibody drug conjugates (ADC) using a panel of selected Innate antibodies against an undisclosed target, with a primary focus in Celiac disease. Takeda will be responsible for the future development, manufacture and commercialization of any potential products developed using the licensed antibodies. As such, the Company considers that the license granted is a right to use the intellectual property, which is granted fully and perpetually to Takeda. The agreement does not stipulate that Innate's activities will significantly affect the intellectual property granted during the life of the agreement. Consequently, the $5.0 million (or €4.6 million) initial payment, received by the Company in May 2023, was fully recognized in revenue as of June 30, 2023. Government funding for research expenditures of €4.1m in the first half of 2024 (€4.9m in the first half of 2023). Operating expenses are €38.7m in the first half of 2024 (€40.6m in the first half of 2023), of which 75.2% (€29.1m) are related to R&D.R&D expenses decreased by €2.4m to €29.1m in the first half of 2024 (€31.5m in the first half of 2023). This change is mainly explained by lower personnel and other R&D expenses by €2.2millions (-15.4%). This decrease is due to an non-recurring amortization charge in the first half of 2023, related to the IPH5201 rights (full amortization of the additional €2.0 million invoice from Orega Biotech following the dosing of the first patient in the Phase 2 MATISSE clinical trial in June 2023). Additionally, direct R&D expenses, which slightly decreased by €0.2 million, remained at €17.1 million, with an acceleration in preclinical spending related to the Antibody-Drug Conjugates (ADC) program offsetting the decrease in expenses related to certain more mature clinical-stage programs. General and administrative (G&A) expenses increased by €0.4m to €9.6m in the first half of 2024 (€9.1m in the first half of 2023) mainly resulting from (i) a €0.4m decrease of personnel expenses mainly due to a reduction of administrative staff, offset by (ii) a €0.3m increase in non-scientific advisory and consulting fees resulting from greater reliance on recruitment agencies, and finally (iii) a €0.5 million increase in other expenses, mainly due to the derecognition of returned spaces in the first half of 2023 (as a reminder, on March 13, 2023, the Company signed an amendment to the lease of the 'Le Virage' building, aimed at reducing the area of leased premises) and the sale of related furniture during the same period, which led to an exceptional reduction in these charges in the first half of 2023. A net financial gain of €1.5m in the first half of 2024 (€2.1m in the first half of 2023). This variance mainly results from the unfavorable evolution of the dollar exchange rate and its impact on foreign exchange recorded during the first half of 2024. The negative currency impact was offset by an increase in the fair value of certain financial instruments. A net loss of €24.8m for the first half of 2024 (net income of €1.7m for the first half of 2023). The table below summarizes the IFRS consolidated financial statements as of and for the six months ended June 30, 2024, including 2023 comparative information.

Phase 2License out/inClinical ResultPhase 1

10 Sep 2024

·www.prnewswire.com

I-Mab Presents Positive Uliledlimab Pharmacokinetics Data at 2024 World Conference on Lung Cancer

- Pharmacokinetic/pharmacodynamic (PK/PD) modeling data from three Phase 1 studies providing dosing support for upcoming clinical trials - Exposure-Response (E-R) Analysis showed a positive correlation between uliledlimab concentration and ORR probability in mNSCLC patients - Randomized Phase 2 study of uliledlimab in combination with pembrolizumab plus chemotherapy expected to begin in 1H 2025 ROCKVILLE, Md., Sept. 10, 2024 /PRNewswire/ -- I-Mab (NASDAQ: IMAB) (the "Company"), a U.S.-based, global biotech company exclusively focused on the development of highly differentiated immunotherapies for the treatment of cancer, today announced a poster presentation of PK/PD modeling data for uliledlimab at the International Association for the Study of Lung Disease (IASLD)'s 2024 World Conference on Lung Cancer (WCLC 2024) held September 7-10, 2024 in San Diego, CA. Uliledlimab (TJ004309) is an antibody designed to target CD73, the rate-limiting enzyme critical for adenosine-driven immunosuppression in the tumor microenvironment. Blocking CD73 allows anti-tumor immunity to proceed without the presence of an adenosine-induced "immunological fog". The WCLC 2024 presentation includes data from uliledlimab PK/PD analyses from three Phase 1 studies including patients with treatment naïve metastatic non-small cell lung cancer (mNSCLC). "The PK/PD analysis presented at WCLC underscores our view that uliledlimab has the potential to be a differentiated, best-in-class, CD73 inhibitor. The data support our dose selection work and upcoming combination studies, with a study of uliledlimab plus pembrolizumab plus chemotherapy expected to begin in the first half of 2025," said Phillip Dennis, MD, PhD, Chief Medical Officer of I-Mab. "We are particularly encouraged by the E-R analysis, which showed a positive relationship between uliledlimab exposure and the probability of an overall response in patients with NSCLC, as well as positive target engagement data and dose proportional PK results. These data, plus a previously presented favorable safety profile and clinical efficacy, fortify our view that uliledlimab has the potential to meaningfully improve the care of patients with mNSCLC." Poster Title: Integrated PK/PD Modeling for Uliledlimab, an Anti-CD73 Monoclonal Antibody, in Non-Small Cell Lung Cancer Patients (Poster #2979) Data are based on analysis of three Phase 1 studies conducted in China evaluating uliledlimab, as a monotherapy and in combination studies with the checkpoint inhibitors, toripalimab or atezolizumab, in patients with advanced cancers, including mNSCLC. Key Findings Include: Most of the simulated population (95%) could achieve the target threshold with 30 mg/kg of uliledlimab Integrated PK/PD modeling and pharmacometrics analyses indicate there is a positive relationship between the probability of overall response and uliledlimab trough concentration in NSCLC patients CD73 receptor occupancy (RO) in peripheral B cells achieved 90% or above and maintained at high levels until the end of treatment The 30 mg/kg dose with a single boost dose on C1D8 provided uliledlimab concentrations that achieved the target concentration of 80 μg/mL immediately after the first dose and maintained this threshold afterward A Ctrough target threshold of 80 μg/mL may be clinically meaningful, associated with PFS benefit and is achievable by a 30 mg/kg initial dose followed by a booster dose on Cycle 1, Day 8 (C1D8) A full copy of the poster is available on the I-Mab website, on the "Innovation, Publications & Presentations" tab. About I-Mab I-Mab (NASDAQ: IMAB) is a U.S.-based, global biotech company exclusively focused on the development of highly differentiated immunotherapies for the treatment of cancer. I-Mab has established operations in Rockville, Maryland. For more information, please visit and follow us on LinkedIn and X. Forward Looking Statements This announcement contains forward-looking statements. These statements are made under the "safe harbor" provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements can be identified by terminology such as "will", "expects", "believes", "designed to", "anticipates", "future", "intends", "plans", "potential", "estimates", "confident", and similar terms or the negative thereof. I-Mab may also make written or oral forward-looking statements in its periodic reports to the U.S. Securities and Exchange Commission (the "SEC"), in its annual report to shareholders, in press releases and other written materials and in oral statements made by its officers, directors or employees to third parties. Statements that are not historical facts, including statements about I-Mab's beliefs and expectations, are forward-looking statements. Forward-looking statements in this press release include, without limitation, statements regarding: the Company's pipeline and capital strategy, including the Company's stock repurchase program; the projected advancement of the Company's portfolio and anticipated milestones and related timing; the market opportunity and I-Mab's potential next steps (including the potential expansion, differentiation, or commercialization) for uliledlimab, givastomig and ragistomig; the Company's expectations regarding the impact of data from ongoing and future clinical trials; the Company's financial condition and results of operations and anticipated changes in the Company's revenues or expenses; the Company's expectations regarding its cash runway; timing and progress of studies and trials (including with respect to patient enrollment); and the availability of data and information from ongoing studies and trials. Forward-looking statements involve inherent risks and uncertainties that may cause actual results to differ materially from those contained in these forward-looking statements, including but not limited to the following: I-Mab's ability to demonstrate the safety and efficacy of its drug candidates; the clinical results for its drug candidates, which may or may not support further development or New Drug Application/Biologics License Application (NDA/BLA) approval; the content and timing of decisions made by the relevant regulatory authorities regarding regulatory approval of I-Mab's drug candidates; I-Mab's ability to achieve commercial success for its drug candidates, if approved; I-Mab's ability to obtain and maintain protection of intellectual property for its technology and drugs; I-Mab's reliance on third parties to conduct drug development, manufacturing and other services; and I-Mab's limited operating history and I-Mab's ability to obtain additional funding for operations and to complete the development and commercialization of its drug candidates, as well as those risks more fully discussed in the "Risk Factors" section in I-Mab's most recent annual report on Form 20-F, as well as discussions of potential risks, uncertainties, and other important factors in I-Mab's subsequent filings with the SEC. All forward-looking statements are based on information currently available to I-Mab. I-Mab undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise, except as may be required by law. I-Mab Contacts SOURCE I-Mab Biopharma WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical ResultImmunotherapyPhase 1AACRPhase 2

09 Sep 2024

·www.innate-pharma.com

Monalizumab data from NeoCOAST-2 Phase 2 study in early-stage NSCLC presented at the WCLC 2024

Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) (“Innate” or the “Company”) today announced that AstraZeneca (LSE/STO/Nasdaq: AZN) presented interim results from the randomized NeoCOAST-2 (NCT05061550) Phase 2 platform study during the 2024 World Conference on Lung Cancer on September 8, 2024. The NeoCOAST-2 platform study is intended to assess the safety and efficacy of neoadjuvant durvalumab alone or combined with novel agents and chemotherapy in resectable, early-stage non-small cell lung cancer (NSCLC), followed by adjuvant treatment with durvalumab with or without the novel agents. The preliminary data of three arms were presented at WCLC, namely: Arm 1: oleclumab in combination with durvalumab and platinum doublet chemotherapy in the neoadjuvant setting and durvalumab plus oleclumab in the adjuvant setting; Arm 2: monalizumab in combination with durvalumab and platinum doublet chemotherapy in the neoadjuvant setting and durvalumab plus monalizumab in the adjuvant setting and; Arm 4: datopotamab deruxtecan in combination with durvalumab and single agent platinum chemotherapy in the neoadjuvant setting, and durvalumab alone in the adjuvant setting. In this preliminary analysis on the first 60 of 72 patients randomized to Arm 2, monalizumab added to durvalumab plus platinum-based chemotherapy doublet induced a pathological complete response rate of 26.7% [95% CI; 16.1–39.7] and a major pathological response rate of 53.3% [95% CI; 40.0–66.3] which are numerically higher than the durvalumab plus platinum doublet approved regimen. Treatment in Arm 2 showed manageable safety profile and no impact on surgical rate. The presentation will be available on Innate’s website, in the publications section. “We’re pleased to see the preliminary results from the NeoCOAST-2 Phase 2 trial presented at WCLC and the encouraging clinical outcomes for patients with early-stage non-small cell lung cancer across all treatment arms,” said Dr Sonia Quaratino, Chief Medical Officer of Innate Pharma. “Monalizumab is the first checkpoint inhibitor targeting the inhibitory receptor NKG2A on NK cells and CD8 T cells. Based on these preliminary results, we remain excited about the potential of extending the clinical benefit of durvalumab in the neoadjuvant/adjuvant setting with the addition of monalizumab in patients with non-small cell lung cancer. We look forward to the final analysis and the translation of these preliminary data to Event Free Survival (EFS) data in due course.” In 2022, an estimated 2.5 million people were diagnosed with lung cancer worldwide1. Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC2,3,4 Stage III NSCLC represents approximately one quarter of NSCLC incidence5. Stage III (locally advanced) NSCLC is commonly divided into three subcategories (IIIA, IIIB and IIIC), defined by how much the cancer has spread locally. Monalizumab is a potentially first-in-class immune checkpoint inhibitor targeting NKG2A receptors expressed on tumor infiltrating cytotoxic CD8+ T cells and NK cells. NKG2A is an inhibitory checkpoint receptor for HLA-E. By expressing HLA-E, cancer cells can protect themselves from killing by NKG2A+ immune cells. HLA-E is frequently overexpressed in the cancer cells of many solid tumors and hematological malignancies. Monalizumab may reestablish a broad anti-tumor response mediated by NK and T cells and may enhance the cytotoxic potential of other therapeutic antibodies6. AstraZeneca obtained full oncology rights to monalizumab in October 2018 through a co-development and commercialization agreement initiated in 2015. The ongoing development for monalizumab is focused on investigating monalizumab in various combination strategies in NSCLC and other malignancies. 1 Ferlay J, Ervik M, Lam F, Laversanne M, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F (2024). Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available from: https://gco.iarc.who.int/today 2 Provencio M, et al. Inoperable Stage III Non-Small Cell Lung Cancer: Current Treatment and Role Of Vinorelbine. J Thorac Dis. 2011;3:197-204 3 Cheema PK, et al. Perspectives on Treatment Advances for Stage III Locally Advanced Unresectable Non-Small-Cell Lung Cancer. Curr Oncol. 2019;26(1):37–42. 4 LUNGevity Foundation. Types of Lung Cancer. Available at https://lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer. Accessed September 2021. 5 EpiCast Report: NSCLC Epidemiology Forecast to 2025. GlobalData. 2016. 6 André et al, Cell 2018

Clinical ResultImmunotherapyPhase 2License out/in

100 Deals associated with Oleclumab

External Link

KEGG	Wiki	ATC	Drug Bank
D10963	Oleclumab	-	DB15088

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Locally Advanced Lung Non-Small Cell Carcinoma	Phase 3	ES	AstraZeneca PLC	07 Feb 2022
Locally Advanced Lung Non-Small Cell Carcinoma	Phase 3	VN	AstraZeneca PLC	07 Feb 2022
Locally Advanced Lung Non-Small Cell Carcinoma	Phase 3	US	AstraZeneca PLC	07 Feb 2022
Locally Advanced Lung Non-Small Cell Carcinoma	Phase 3	FR	AstraZeneca PLC	07 Feb 2022
Locally Advanced Lung Non-Small Cell Carcinoma	Phase 3	UA	AstraZeneca PLC	07 Feb 2022
Locally Advanced Lung Non-Small Cell Carcinoma	Phase 3	PL	AstraZeneca PLC	07 Feb 2022
Locally Advanced Lung Non-Small Cell Carcinoma	Phase 3	IT	AstraZeneca PLC	07 Feb 2022
Locally Advanced Lung Non-Small Cell Carcinoma	Phase 3	JP	AstraZeneca PLC	07 Feb 2022
Locally Advanced Lung Non-Small Cell Carcinoma	Phase 3	AU	AstraZeneca PLC	07 Feb 2022
Locally Advanced Lung Non-Small Cell Carcinoma	Phase 3	CO	AstraZeneca PLC	07 Feb 2022

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03267589 (Pubmed) Manual	Phase 2	Recurrent ovarian cancer	25	oleclumab and durvalumab	(aumolovztd) = xepghmryup nmjcvvvlpp (lxktdzkhil ) View more	Negative	23 Aug 2024
NCT03611556 (Pubmed) Manual	Phase 1/2	Metastatic Pancreatic Ductal Adenocarcinoma	170	gemcitabine plus nab-paclitaxel	(jdddhgxktu) = oixcojunfu bdrmdbppny (unhhnnsowh ) View more	Negative	06 Aug 2024
				oleclumab (RP2D)+ gemcitabine plus nab-paclitaxel	(jdddhgxktu) = yjbkvnqsml bdrmdbppny (unhhnnsowh ) View more
NCT04068610 (COLUMBIA-1, Pubmed) Manual	Phase 2	Metastatic Microsatellite Stable Colorectal Carcinoma	52	durvalumabf-care	(jxvthrdjtw) = xvnslrugxn rcjscrfjre (ygnguwodbk, 26.6 - 66.6) View more	Negative	25 Jul 2024
				Standard-of-care plus durvalumab and oleclumab (experimental arm)	(jxvthrdjtw) = gnsekadslw rcjscrfjre (ygnguwodbk, 40.6 - 79.8) View more
NCT03822351 (COAST, ASCO2024) Manual	Phase 2	Unresectable Lung Non-Small Cell Carcinoma	189	durvalumab	(ylqhojqhis) = kausczykup lkpjyxqkvj (wfbiuqojgm, 14.3 - 35.9) View more	Positive	24 May 2024
				durvalumab+oleclumab	(ylqhojqhis) = ljcdjntseu lkpjyxqkvj (wfbiuqojgm, 23.1 - 48.4) View more
NCT04089553 (Pubmed) Manual	Phase 2	Metastatic castration-resistant prostate cancer Third line	59	AZD4635 + durvalumab	(hjqzpjrbbv) = nlrksisxza ankojwdvih (uinbummzms ) View more	Negative	02 Mar 2024
				AZD4635 + oleclumab	(obkzwwdwqr) = usiddzxwrs ifnzyqufdv (vpklcigbbe ) View more
NCT03334617 (HUDSON, Pubmed) Manual	Phase 2	Advanced Lung Non-Small Cell Carcinoma	268	Durvalumab-ceralasertib	(vyihfkeiva) = ltrijidntk fpuqupktyt (grvombdfju ) View more	Positive	01 Mar 2024
				Durvalumab-olaparib or Durvalumab-danvatirsen or Durvalumab-oleclumab	(vyihfkeiva) = spjgtasehh fpuqupktyt (grvombdfju ) View more
NCT04068610 (COLUMBIA-1, CTgov)	Phase 1/2	Metastatic Microsatellite Stable Colorectal Carcinoma	61	FOLFOX+Bevacizumab+Durvalumab+Oleclumab (Part 1 (S1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab)	sbbemgaihh(hskfzbbiia) = gqzktdjuyz alqanktwlt (fiavgcpcwh, epegfycmin - skvawcxzsm) View more	-	15 Nov 2023
				FOLFOX+Bevacizumab (Part 2 (C1): FOLFOX + Bevacizumab)	sxubktgvnk(kxlfdgrgvl) = jpgmcsqqun unvlxlrdfy (budtgrxxpg, mbovurokzd - etcwhcqnhm) View more
NCT03611556 (ASCO2023) Manual	Phase 1/2	Metastatic Pancreatic Ductal Adenocarcinoma	195	gemcitabine+nab-paclitaxel (Arm A1)	(gvvobcrqko) = jcanttubpw memicqfbfi (hghylkamkd, 18.2 - 41.9) View more	Positive	31 May 2023
				gemcitabine+nab-paclitaxel+oleclumab (Arm A2)	(gvvobcrqko) = ayxoakbfmq memicqfbfi (hghylkamkd, 9.6 - 37.3) View more
NCT03381274 (Pubmed)	Phase 2	EGFR T790M Mutation Positive Non-Small Cell Lung Carcinoma	43	Oleclumab 1500 mg	(xoxtfvryom) = opzcapwjgs axecvfiwiq (tqjtdspvmp )	Positive	11 Jan 2023
				Oleclumab 3000 mg	(xoxtfvryom) = wtvfgwvusb axecvfiwiq (tqjtdspvmp )
NCT04068610 (COLUMBIA-1, ESMO_IO2022) Manual	Phase 1/2	Metastatic Microsatellite Stable Colorectal Carcinoma First line Microsatellite-Stable	52	Durvalumab 1500 mg+Oleclumab 3000 mg+Bevacizumab+ FOLFOX	(ssupljkges) = anhpoqacql dqtheoweqk (fslpdgstlq, 40.6 - 79.8) View more	Positive	08 Dec 2022
				Bevacizumab+ FOLFOX	(ssupljkges) = cgzabdkcrf dqtheoweqk (fslpdgstlq, 24.4 - 65.1) View more

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