On April 17, 2023 Data of InnoCare’s (HKEX: 09969; SSE: 688428) reported that its robust oncology pipelines were presented at the 2023 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, InnoCare Pharma, APR 17, 2023, View Source [SID1234630210]).

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Oral Presentation:

ICP-490 is a highly potent and selective IKZF1/3 degrader with robust anti-tumor activities against multiple myeloma and non-Hodgkin’s lymphoma

Abstract Number: 3427

In various multiple myeloma (MM) and non-Hodgkin’s lymphoma (NHL) tumor models, ICP-490 demonstrates superior tumor killing activities, including overcoming lenalidomide resistance. ICP-490 is now in phase I clinical trial.

Cell viability assays reveal robust in vitro efficacies of ICP-490 against various MM and NHL(including DLBCL) cell lines with nanomolar IC50. It also exhibits potent anti-proliferative activity in lenalidomide-resistant cell lines. In contrast to its tumor killing effect, ICP-490 shows no cytotoxicity against normal human cells. In vivo efficacy studies have further confirmed the effectiveness of ICP-490 against various MM and DLBCL xenografts.

The immune modulation activity of ICP-490 has also been illustrated in a combinatory treatment with monoclonal antibody, where low dose of ICP-490 leads to robust induction of IL-2 and granzyme B, and much improved efficacy of anti-CD38 mAbs in MM; in NHL, ICP-490 demonstrates synergistic tumor killing effects when combined with BTK inhibitor orelabrutinib.

ICP-490 has overall favorable pharmacokinetic parameters with high oral bioavailability.

Poster Presentation 1:

Combination of BTK inhibitor orelabrutinib, anti-CD19 antibody tafasitamab, and IMiD lenalidomide for the treatment of B cell malignancies

Abstract Number: 4013

R-CHOP has been widely recognized as effective first-line treatment for DLBCL. However, 30-50% of the patients are either refractory or eventually develop relapsed diseases (r/r DLBCL). Multiple clinical trials of orelabrutinib are being carried out for the treatment of DLBCL, including the first-line treatment of MCD subtype of DLBCL. An exploratory study to evaluate the safety and efficacy of orelabrutinib, tafasitamab and lenalidomide combinations in patients with relapsed/refractory non-Hodgkin’s lymphoma (NHL) is ongoing.

The highly selective BTK inhibitor orelabrutinib is a superior combinatory partner with antibody therapeutics whose mechanism of action is highly dependent on ADCC. Orelabrutinib is a highly selective BTK inhibitor with no inhibition effect on T cells, which confers its ability to enhance or retain the ADCC activity of tafasitamab. Combination of orelabrutinib with tafasitamab and/or lenalidomide also leads to synergistic tumor lysis activity, with or without the presence of immune effector cells. Confirmation of the synergistic effects of orelabrutinib with tafasitamab and lenalidomide in various preclinical models has provided scientific rationales for testing the combinatory treatment in clinical studies.

Poster Presentation 2:

Preclinical development of SHP2 allosteric inhibitor ICP-189

Abstract Number: 4012

ICP-189 is a novel allosteric inhibitor of SHP2 with broad-spectrum anti-tumor activities as a single agent or in combination with other targeted or immune modulating anti-cancer therapeutics. ICP-189 is now in phase I clinical trial in China and United States.

In a phosphatase profiling assay, ICP-189 efficiently inhibits the catalytic activity of SHP2, with no significant effects on 21 other tested tyrosine and serine/threonine phosphatases, indicating its high selectivity for SHP2. ICP-189 has demonstrated robust in vitro efficacies in a panel of tumor cell lines bearing activated RTK, RAS, NF1 loss-of-function, or BRAF class III mutations. It has also exhibited synergistic tumor killing effects in combination with EGFR, KRASG12C, MEK and CDK4/6 inhibitors.

The in vivo efficacy of ICP-189 is well accompanied by pharmacodynamic modulations, where ICP-189 exposure levels correlate with reduced p-ERK and DUSP6 mRNA levels in tumors.

The pharmacokinetic parameters of ICP-189 are overall favorable, with high oral bioavailability.

Detailed abstracts can be found at AACR (Free AACR Whitepaper) official website.

On April 17, 2023 OSE Immunotherapeutics SA (ISIN: FR0012127173; Mnemo: OSE) reported three presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Orlando (Florida), April 14-19, 2023 (Press release, OSE Immunotherapeutics, APR 17, 2023, View Source [SID1234630209]). The presentations include the first data on biomarker analyses from the Phase 1 study of BI 765063 (anti-SIRPα monoclonal antibody on the CD47/SIRPα pathway) in advanced solid tumors. Two other presentations report the latest preclinical updates on OSE-127 (anti-IL-7 receptor antagonist) in hematology and on BiCKI-IL-7 (new bifunctional therapy targeting PD1 and IL-7).

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In addition, preclinical characterization data on CLEC-1 (new myeloid immune checkpoint) binding mechanism will also be presented on April 19.

Nicolas Poirier, Chief Executive Officer of OSE Immunotherapeutics, comments: "We are very pleased to share our latest scientific advances with the leading international cancer scientific community. The solid clinical and preclinical data derived from our innovative research programs in immuno-oncology demonstrate our continued commitment and progress to delivering first-in-class immunotherapies for cancer patients in high need for new therapeutic options."

BI 765063, a first-in-class selective SIRPα inhibitor on the SIRPα/CD47 myeloid pathway targeting myeloid cells in immuno-oncology, with a strong biological rationale for clinical response.

The escalation Phase 1 clinical trial data on selective SIRPα antagonist BI 765063 showed preliminary clinical efficacy results in monotherapy and in combination with PD1 inhibitor ezabenlimab in patients with advanced solid tumors. A biomarker analysis from this escalation Phase 1 study was performed to characterize the impact of BI 765063 on the tumor environment.

The AACR (Free AACR Whitepaper) presentation featured analysis results showing a predictive response of identified biomarkers:

High levels of myeloid cells expressing SIRPα (CD11b+, SIRPα+ myeloid cells) in tumor microenvironment at baseline (but not CD47 tumor cell expression) correlate with longer survival. MDSC (Myeloid-Derived Suppressor Cells) signature in tumor microenvironment at baseline correlates also with clinical response.

Three clinical studies of BI 765063 in combination are currently being conducted:

– NCT05249426: in patients with 1st or 2nd line hepatocellular carcinoma in combination with anti-PD1 ezabenlimab +/- VEGF/Ang2 inhibitor and 2nd line head and neck squamous cell carcinoma in combination with cetuximab or chemotherapy and who received no prior anti-PD-L1 inhibitors (in the United States, Europe and Japan).
– NCT03990233: in patients with microsatellite stable (MSS) advanced colorectal cancer and MSS advanced endometrium cancer whose disease relapsed after standard of care and who received no prior anti-PD-L1 inhibitors (in Europe) (1).
|- NCT04653142: in patients with solid tumors (in Japan).

OSE-127, a monoclonal immunomodulatory antibody antagonist of IL-7 receptor, represents a novel promising immunotherapy option in Acute Lymphoblastic Leukemia. (2)

The CD127 receptor is over-expressed by acute lymphoblastic leukemia and is efficiently targeted by the IL-7R-antagonist OSE-127 through macrophage-mediated antibody dependent phagocytosis. Targeting IL-7R CD127 is a promising novel strategy in B-Cell Precursor ALL (BCP-ALL) and T-ALL (T-Cell ALL) since CD127 signalling is important for B- and T-cell development, survival and proliferation. Despite the favourable prognosis of BCP-ALL, relapse remains a clinical challenge and novel targeted immunotherapy options are urgently needed. T-ALL is an aggressive haematological cancer for which treatment options are limited at relapse.

The poster presentation concluded on the strong rationale that OSE-127 may represent a powerful novel immunotherapy option for ALL patients based on a unique dual mechanism of action. This antibody both blocks oncogenic interleukin-7 fuel pathway and simultaneously triggers macrophage-driven phagocytosis of leukemic cells.

This research program, conducted on patient-derived xenograft experiments, is led by OSE Immunotherapeutics in collaboration with Pr. Denis Schewe (Head of the Pediatrics Department, Otto-von-Guericke-University, Magdeburg and formerly from the University Medical Center Schleswig-Holstein of Kiel) and Dr. Lennart Lenk (Department of Pediatrics I, Christian-Albrechts University Kiel and University Medical Center Schleswig-Holstein, Kiel).

BiCKIIL-7, a bifunctional immunotherapy targeting PD1 and IL-7, represents a high potential asset for cancer patients suffering from immune escape following checkpoint inhibitor treatments.

BiCKIIL-7, the most advanced candidate from OSE Immunotherapeutics’ BiCKI platform, is a novel bifunctional therapy which targets PD1 and at the same time selectively deliver IL-7 pro-survival cytokine to tumor-specific T-cells expressing PD1. BiCKIIL-7 restores exhausted T-cell function, disarms Treg suppressive activity and extends stem-like memory T-cells, the key T-cell subpopulation associated with anti-PD-(L)1 clinical responses.

The presentation reports that anti-PD1/IL-7v BiCKI-IL-7 showed significant monotherapy anti-tumor efficacy in different in vivo models. In addition, BiCKI-IL-7 showed significant anti-tumor efficacy post-anti-PD-(L)1 failure in a preclinical model, highlighting the clinical potential of BiCKI-IL-7v in immune checkpoint inhibitor resistant patients.

These results validate the rationale of selective delivery of IL-7 to PD1 tumor-specific T-cells to limit risk of I-O/I-O immunotoxicity and sustain long-lasting proliferation and survival of stem-like CD8 T-cells to strengthen anti-PD-(L)1 therapy.

This Phase 1 clinical trial with BI 765063 is being conducted by OSE Immunotherapeutics as part of a collaboration and license agreement under which Boehringer Ingelheim obtained exclusive rights to BI 765063.
In parallel, OSE-127 is currently being developed in clinical stage in partnership with Servier. Two clinical studies are ongoing in inflammatory diseases: a phase 2a study conducted in primary Sjögren’s syndrome by Servier and a Phase 2 study conducted in ulcerative colitis by OSE Immunotherapeutics.
Poster presentation details:

Poster BI 765063

Title: "Predictive response biomarkers from Phase I clinical trial of a SIRPalpha inhibitor BI765063, stand-alone and in combination with ezabenlimab, a PD1 inhibitor, in patients with advanced solid tumors"
Session Category: Clinical Research Excluding Trials
Session Title: Biomarkers of Therapeutic Benefit 2
Date & Time: April 17, 2023 – 9:00 AM – 12:30 PM
Location: Poster Section 39, Poster Board 3
Poster Number: 2129

Poster OSE-127

Title: "CD127 is expressed by acute lymphoblastic leukemias and is efficiently targeted by the IL7R-antagonist OSE-127 through macrophage-mediated antibody dependent phagocytosis"
Session Category: Immunology
Session Title: Therapeutic Antibodies 3
Session Date and Time: April 17, 2023 – 1:30 PM – 5:00 PM
Location: Poster Section 24
Poster Board Number: 4

Poster BiCKI-IL-7

Title: "Anti-PD-1/IL-7v bispecific antibody promotes TCF1+ stem like CD8 T cells expansion and long-lasting in vivo efficacy"
Session Category: Immunology
Session Title: Therapeutic Antibodies 3
Session Date and Time: April 17, 2023 – 1:30 PM – 5:00 PM
Location: Poster Section 24
Poster Board Number: 2

Poster CLEC#1*

Title: "CLEC-1 inhibitory myeloid checkpoint blockade enhances antitumor responses and tumor phagocytosis by macrophages""
Session Category: Immunology
Session Title: Immune Checkpoints
Session Date and Time: April 19, 2023 – 9:00 AM – 12:30 PM
Location: Section 23
Poster Board Number: 2

Poster CLEC#2*

Title: "TRIM21 is a novel endogenous partner of the inhibitory myeloid checkpoint CLEC-1 involved in tumor antigen cross-presentation"
Session Category: Immunology
Session Title: Immune Checkpoints
Session Date and Time: April 19, 2023 – 9:00 AM – 12:30 PM
Location: Poster Section 23
Poster Board Number: 9
* Collaborative academic program between OSE Immunotherapeutics and Dr Elise Chiffoleau’s research teams (Center for Research in Transplantation and Translational Immunology (CR2TI), UMR1064, INSERM, Nantes University at Nantes University Hospital, View Source).

On April 17, 2023 Dragonfly Therapeutics, Inc., a clinical stage biotechnology company developing novel immunotherapies, reported the April 13th publication of preclinical data in Cell Press’s Med supporting DF6002 as a promising treatment option for cancer patients (Press release, Dragonfly Therapeutics, APR 17, 2023, View Source [SID1234630208]). DF6002 is Dragonfly’s novel half-life extended interleukin-12 (IL-12) cytokine immunotherapy, currently in Phase 1 clinical development with dose escalation progressing successfully in patients as a monotherapy and in combination with nivolumab, in the U.S. and in Europe.

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Systemic IL-12 cytokine therapy was historically associated with severe toxicities due to its narrow therapeutic index. Dragonfly’s preclinical data demonstrates that DF6002 is well tolerated when administered systemically and results in potent anti-tumor responses in multiple preclinical models as monotherapy and in combination with checkpoint inhibitors. Dragonfly’s novel DF6002 IL-12 is designed for half-life extension which alters IL-12’s pharmacodynamic response profile and expands its therapeutic index. "We are excited about these findings, which provide compelling evidence supporting our ongoing Phase I clinical trial, which is evaluating the safety and tolerability of DF6002 in patients with advanced solid tumors," said Joseph Eid, MD, Dragonfly’s President of Research and Development. "Given the encouraging profile we have seen both in preclinical models and in the clinic to date, we are accelerating DF6002’s development across a range of indications and combinations."

About DF6002
DF6002, Dragonfly’s extended half-life IL-12 cytokine, is an investigational immunotherapy being evaluated alone and in combination with nivolumab in participants with locally advanced or metastatic solid tumors (NCT04423029). DF6002 is a monovalent IL-12 immunoglobulin Fc fusion protein proposed to achieve strong anti-tumor efficacy by establishing an inflammatory tumor microenvironment necessary for productive anti-tumor responses. DF6002 has the potential to stimulate effective anti-tumor immunity in patients who are not eligible or not adequately responding to current therapies. DF6002 is the most advanced in a pipeline of cytokines that Dragonfly is developing to address the high unmet need in patients with advanced cancer.

On April 17, 2023 WuXi Biologics ("WuXi Bio") (2269. HK), a leading global Contract Research, Development, and Manufacturing Organization (CRDMO) and its subsidiary WuXi XDC congratulate their partner DualityBio, a clinical-stage biotech company focusing on the discovery and development of next generation ADC therapeutics for patients with cancer and autoimmune diseases, on entering into exclusive license and collaboration agreements with German based BioNTech, a next generation immunotherapy company pioneering novel therapies for cancer and other serious diseases, for two investigative antibody-drug conjugates ("ADC") therapeutics (Press release, WuXi Biologics, APR 17, 2023, View Source [SID1234630207]).

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WuXi Bio provided technical services, based on the companies’ versatile integrated service platforms, to support various manufacturing and process development activities of these ADC product candidates.

"We congratulate DualityBio for the license agreements for two of their ADC candidates and are pleased to have been able to support DualityBio with our diverse services and expertise in the field of ADC products," commented Dr. Chris Chen, CEO of WuXi Biologics, "Over the last couple of years, our advanced technology platforms and high-quality services have supported our clients to win the trust of their partners, which facilitates multiple global collaborations between biotech and multinational pharmaceutical companies."

"Congratulations to DualityBio on reaching the license agreements with BioNTech. We are honored to support innovative partners such as DualityBio in advancing ADCs with our premier quality systems and extensive expertise," commented Dr. Jimmy Li, CEO of WuXi XDC, "Innovative and differentiated ADCs are emerging driven by unmet medical needs. As a global CRDMO dedicated to bioconjugates, we’ll continue to accelerate and transform the discovery, development and manufacturing of bioconjugates, supporting our global partners for the benefit of patients globally."

On April 17, 2023 Medivir AB (NASDAQ Stockholm: MVIR), a pharmaceutical company focused on developing innovative treatments for cancer in areas of high unmet medical need, reported that a poster entitled ‘A triple combination of fostrox (MIV-818) with immune checkpoint and kinase inhibition shows increased anti-tumor efficacy in vivo,’ will be presented today at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting by Fredrik Öberg, CSO at Medivir (Press release, Medivir, APR 17, 2023, View Source [SID1234630206]).

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Fostroxacitabine bralpamide (fostrox) is an orally administered liver-targeted prodrug currently undergoing a phase 1/2a clinical study in advanced hepatocellular carcinoma (HCC), in combination with Keytruda (anti-PD1) or Lenvima (kinase inhibitor) (NCT0341818). In previous studies, Fostrox has shown significantly increased anti-tumor effect in combination with both anti-PD1 and kinase inhibitors in non-clinical tumor models, which opens the door for a potentially further enhanced tumor effect with a triple combination.

The poster supports this potential as it exhibits that fostrox combined with both anti-PD1 and Lenvima shows a synergistic anti-tumor effect in a non-clinical tumor model characterized by the same low, underlying DNA damage seen in patients with HCC. The poster also shows that fostrox induces increased tumor infiltration of CD8+ T cells as well as increased expression of PD-L1 and LAG-3, indicating increased immune-mediated antitumor activity. The results indicate a potential for triple combination of anti-PD1 and Lenvima with fostrox in the treatment of HCC.

"Although existing combination treatments for HCC can prolong patients’ lives, far from all patients respond to the treatment. In order for more patients to obtain a satisfactory effect on their treatment, new combination options with several different, additive mechanisms of action are needed. Fostrox, with its unique, liver-targeted activity, opens up for new combinations with three different approaches to effectively treat HCC," says Pia Baumann, CMO at Medivir.

The poster will be available on Medivir’s website after the presentation.

For additional information, please contact
Magnus Christensen, CFO, Medivir AB
Telephone: +46 8 5468 3100
E-mail: [email protected]

About fostrox
Fostrox is a pro-drug designed to selectively treat liver cancers and to minimize side effects. It has the potential to become the first liver-targeted and orally administered drug for patients with HCC and other forms of liver cancer. Fostrox has completed a phase 1b monotherapy study, and a combination study in HCC currently ongoing.

About primary liver cancer
Primary liver cancer is the third leading cause of cancer-related deaths worldwide and hepatocellular carcinoma (HCC) is the most common cancer that arises in the liver. Although existing therapies for advanced HCC can extend the lives of patients, treatment benefits are insufficient and death rates remain high. There are 42,000 patients diagnosed with primary liver cancer per year in the US and current five-year survival is
11 percent. HCC is a heterogeneous disease with diverse etiologies, and lacks defining mutations observed in many other cancers. This has contributed to the lack of success of molecularly targeted agents in HCC. The limited overall benefit, taken together with the poor overall prognosis for patients with intermediate and advanced HCC, results in a large unmet medical need.