On April 9, 2022 Rhizen Pharmaceuticals AG (Rhizen), a Switzerland-based privately held, clinical-stage oncology & inflammation-focussed biopharmaceutical company, reported the release of data on its differentiated next-generation clinical-stage PARP (Poly ADP-Ribose Polymerase) and DHODH (DiHydro Orotate DeHydrogenase) inhibitor programs at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2022 Annual Meeting (Press release, Rhizen Pharmaceuticals, APR 9, 2022, View Source [SID1234611848]). Rhizen’s poster presentations describe the preclinical characterization and differentiated features of its novel PARP inhibitor (RP12146) and preclinical data supporting the broad positioning of its DHODH inhibitor (RP7214) in AML.

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Rhizen had earlier indicated that its PARP program had demonstrated differentiated IND enabling preclinical safety. The additional preclinical data being presented at AACR (Free AACR Whitepaper) 2022 suggests that this differentiated safety may be due to the lower bone marrow distribution of RP12146 and concomitantly lower haematological toxicity. "We believe RP12146’s safety differential has allowed us to progress through the dose escalation study more efficiently. Further, the emerging data from our ongoing phase 1 dose escalation study is encouraging & corroborative with robust target engagement and safety observed so far. We believe that this differentiation, as it translates more fully in the clinic, may allow us to explore the full potential of PARP inhibition across indications given RP12146’s potentially wide therapeutic window," said Swaroop Vakkalanka, Founder & CEO of Rhizen Pharma.

Rhizen indicated that its DHODH inhibitor, RP7214 has robust activity as a single agent in inducing tumor volume & size reduction and differentiation of AML blasts consistent with its mechanism of action. RP7214 also potentiates the activity of standard of care AML agents such as cytarabine, venetoclax and azacytidine. Swaroop added that "We have initiated a phase 2 study to explore RP7214 in combination with azacytidine in relapsed/refractory AML, CMML and MDS patients. The potential of DHODH inhibition as a therapeutic modality in AML remains unfulfilled and we expect RP7214 can eventually realize that potential. We believe elderly patients who are ineligible for frontline chemotherapy and maintenance settings represent areas of unmet need that RP7214 can address."

Details on Rhizen Pharma’s posters at AACR (Free AACR Whitepaper) are as follows:

Abstract Number: 1762
Title: Activity of RP7214, a novel, selective, and potent small molecule inhibitor of DHODH, in AML
Session: Small Molecule Therapeutic Agents
Poster Number: 5492
Abstract Number: 1766
Title: Activity of RP12146, a novel, selective, and potent small molecule inhibitor of PARP 1/2, in solid tumors
Session: Small Molecule Therapeutic Agents
Poster Number: 5493

On April 8, 2022 iOnctura SA, a clinical-stage oncology company targeting core resistance and relapse mechanisms at the tumor-stroma-immune interface, has reported preclinical data that shows its autotaxin inhibitor IOA-289 both inhibits pancreatic cells directly and inhibits the cancer-promoting activity of secreted factors from Cancer-Associated Fibroblasts (CAFS) (Press release, iOnctura, APR 8, 2022, View Source [SID1234640236]). The data will be shared via a poster (#2636) at the annual meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) taking place on April 8-13, 2022 in New Orleans, Louisiana.

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Autotaxin (ATX) is a secreted glycoprotein that hydrolyzes Lysophosphatidylcholine (LPC) to Lysophosphatidic Acid (LPA). LPA is a tumor cell growth activator and survival promotor. The AACR (Free AACR Whitepaper) presentation demonstrates that by preventing LPA production, IOA-289 has a direct effect on pancreatic cancer cell lines (PDAC cells), inhibiting their growth in vitro.

LPA also modulates the tumor stroma which enables tumors to evade host immunity and impairs patients’ responses to therapy. Cancer Associated Fibroblasts (CAFs) are particularly important drivers of this effect and are responsible for supporting and promoting the growth of cancer cells via the secretion of soluble mediators such as lipids (eg LPC) and cytokines. iOnctura’s data shows that addition of IOA-289 to CAF cultures inhibits the ability of these secreted factors to promote cancer cell growth in vitro. Further experiments with activated fibroblasts show that IOA-289 inhibits IL-6 and PAI-1 secretion, and likely contributes to the in vivo anti-tumorigenic nature of IOA-289.

These results provide further evidence for the mode of action of IOA-289 which acts directly on tumor cells and also modulates the immunosuppressive fibrotic microenvironment. IOA-289 represents a novel therapeutic strategy for the treatment of highly fibrotic, immunosuppressive ("cold") cancer indications such as pancreatic cancer that are resistant to therapy. A Phase I clinical study of IOA-289 in pancreatic cancer is in planning.

The poster presentation (#2636) at AACR (Free AACR Whitepaper) is entitled "Targeting Autotaxin to Suppress Stromal Signaling in the Tumor Microenvironment to Improve Outcome to Therapy in Fibrotic Tumor Types." The poster will be presented on Tuesday Apr 12, 2022 between 9:00 AM and 12:30 PM in New Orleans Convention Center, Exhibit Halls D-H, Poster Section 24. The abstract is available in the AACR (Free AACR Whitepaper) Online Proceedings planner and will also be published in the online supplement to the AACR (Free AACR Whitepaper) journal Cancer Research approximately eight weeks after the AACR (Free AACR Whitepaper) annual meeting.

The e-poster presentation will be available on iOnctura’s website following the meeting.

Contacts

iOnctura
Catherine Pickering
Chief Executive Officer
T: +41 79 952 72 52
E: [email protected]
Press Relations
Jeremy Nieckowski
LifeSci Advisors
T: +41 79 699 97 27
E: [email protected]
iOnctura SA is clinical stage oncology company targeting core resistance and relapse mechanisms at the tumor-stroma-immune interface. iOnctura’s best-in-class drug development programs combine immune-mediated and direct anti-tumor activity to deliver molecules with superior clinical efficacy and safety in oncology. Its lead program, IOA-244 is the only semi-allosteric PI3Kδ specific, orally dosed, small molecule inhibitor that is being developed in solid and hematological malignancies to address tumor and stroma induced immune suppression. IOA-244 is currently in Part B of a Phase 1 study. iOnctura’s second program, IOA-289, is an oral small molecule that inhibits the cross-talk between the tumor and its stroma and is in a Phase 1 clinical study. iOnctura is backed by blue chip investors including M Ventures, Inkef Capital, VI Partners, Schroders Capital, and 3B Future Health Fund. For more information, please visit iOnctura’s website.

IOA-289, originally licensed from Cancer Research UK, is a next generation oral small molecule autotaxin inhibitor that has been investigated in healthy volunteers in study AION 01 trial (ClinicalTrials.gov Identifier: NCT05027568). A phase 1 clinical study in pancreatic cancer patients is in preparation. iOnctura has undertaken extensive validation of the autotaxin inhibition mechanism in multiple solid tumor preclinical models.

Pancreatic cancer (PDAC): Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer accounting for approximately 90% of cases. PDAC has a poor prognosis, with less than 5% of patients surviving beyond five years after diagnosis. There are over 50,000 diagnoses of pancreatic cancer each year in the United States and over 65,000 in the EU5.

On April 8, 2022 BroadenBio Co., Ltd. (BroadenBio) reported the completion of PreA+ round of financing of tens of millions (CNY) (Press release, BroadenBio, APR 8, 2022, View Source [SID1234640198]). The financing was led by the original shareholder Tao Capital, followed by Minkang Health Technology, and the original shareholder Lapam Capital continued to increase investment.

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The funding will primarily be used for the Phase 1 clinical trial of the potentially Best-in-Class (BIC) investigational drug BB102. In addition, the investment will also be used in the development of international cutting-edge small molecule inhibitors of intracellular immune checkpoint, and the preclinical study of globally First-in-Class (FIC) small molecule drug candidates that play immune activation and tumor suppression dual functions, as well as establishing a top-level immunology and small molecule coupling technology platform.

"We are very grateful to all investors, to Lapam Capital and Tao Capital, the well-known investment institutions in the industry, for their long-term support and companionship," said Xingmin Zhang, M.D., Ph.D., founder and Chief Executive Officer of BroadenBio. "BroadenBio has always been adhering to the original intention of its establishment, Gathering Talents, For Innovation, applying our unique technology platforms in the discovery and development of FIC and BIC innovative drugs, benefiting human health with immune technology."

Since its foundation, the company’s R&D pipeline has covered various fields such as oncology, autoimmune disease, and infection. Characteristic technology platforms are becoming increasingly perfect, and the R&D center has begun to take shape.

On April 8, 2022 AbClon reported that the company has partnered with the National Cancer Center (NCC) to develop a CAR-T (Chimeric Antigen Receptor-T) cell therapy for solid cancer and target Claudin (CLDN)-18.2 antigen (Press release, AbClon, APR 8, 2022, View Source [SID1234638630]).

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According to the company, the recent breakthrough success of CAR-T cell therapy for blood cancer has accelerated CAR-T research to treat intractable solid cancer. However, due to various difficulties, such as the micro-tumor environment of solid cancer, there have been no positive clinical results shown in the blood cancer field.

The two sides agreed to fully mobilize each other’s proprietary platform technology to develop a CAR-T cell therapy to treat intractable solid cancer.

The NCC research team plans to develop a platform technology that activates the killing ability of T cells only against cancer cells and a source technology for gene therapy using CAR-T cells that target antigens that exist only in cancer cells.

Abclon plans to develop a CAR-T cell therapy targeting the specific antigen Claudin-18.2 based on NCC’s technology.

The two parties plan to apply the developed method in treating solid metastatic cancer that is refractory to existing treatment.

AbClon stressed that Professor Jung Jun-ho at Seoul National University College of Medicine, an authority in antibody-drug and CAR-T cell therapy research, will participate in developing antibodies among the constituents of CAR that will act on the Claudin-18.2 antigen.

"Since Claudin-18.2 is overexpressed in gastric and pancreatic cancers, we have judged the antigen as a potential target to solve the unmet needs of patients with intractable solid cancer," Professor Jung said.

An AbClon official said, "In addition to the blood cancer treatment currently in clinical trials, the company plans to provide various treatment opportunities to patients by successfully developing a solid cancer CAR-T cell treatment."

The joint research project with NCC will serve as an opportunity for the company to leap forward as a global leader in CAR-T cell therapy, he added.

On April 8, 2022 The board of directors (the "Board") of Sino Biopharmaceutical Limited (the "Company", together with its subsidiaries, the "Group") reported that "TQ-B3525", an innovative drug self-developed by the Group, has been included by the Center for Drug Evaluation (the "CDE") of the National Medical Products Administration of China in the list of breakthrough therapy drugs (Press release, Sino Biopharmaceutical, APR 8, 2022, View Source(e)_0407_1829(2).pdf [SID1234633501]). The indication is relapsed/ refractory follicular lymphoma that has failed at least two prior lines of therapy.

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TQ-B3525 is a novel and selective oral PI3K (phosphatidylinositol 3-kinase) α/δ inhibitor. Studies have shown that PI3K is closely associated with tumours. TQ-B3525 is a dual inhibitor of PI3K catalytic subunits α/δ. It can not only overcome the drug resistance problem caused by the increase of PI3Kα subunit activity when inhibiting PI3Kδ subunit alone, but also significantly reduce the toxicity compared with PI3K pan-inhibitors. Currently, the Group has initiated a number of clinical studies on TQ-B3525 in China, mainly targeting haematological tumours, and some of them have entered Phase II clinical trials.

The CDE has established the Procedure for Breakthrough Therapy Drugs to encourage research and development of new drugs to meet clinical needs and to expedite the review and approval of new drug varieties. Follow-up communication and review and approval of the innovative drugs that have been included as breakthrough therapy drugs can be carried out in accordance with the accelerated procedures.