On December 21, 2022 Celyad Oncology (Euronext & Nasdaq: CYAD) (the "Company"), a biotechnology company focused on the discovery and development of innovative technologies for chimeric antigen receptor (CAR) T-cell therapies, reported an update on its Celyad 2.0 business strategy which has been adopted and implemented over the last few months (Press release, Celyad, DEC 21, 2022, View Source [SID1234625470]).

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In keeping with this strategy, the Company intends to focus on maximizing its valuable intellectual property (IP) estate, and strengthening its research focus.

The Company has compiled a foundational and broad IP estate that controls key aspects of developing therapies in the allogeneic cell therapy space. The patents around allogeneic CAR T-cell therapies and NKG2D-based therapies provide an avenue to develop intellectual property programs and to partner with outside parties around the licensing of these patents.

In addition to IP partnering transactions, Celyad 2.0 will prioritize discovery research in areas of expertise where it can leverage the differentiated nature of its platforms. The Company is implementing a differentiated and innovative strategy, tackling the major current limitations of CAR T-cell therapies. This strategy includes:
Multiplexing approach of the short hairpin RNA (shRNA) platform, allowing multiple genes, including essential and functional genes, to be modulated simultaneously;

Dual CAR development of a next-generation NKG2D-based CAR which may help to overcome resistance and immune escape often observed with traditional single targeting approaches; and
Development of B7-H6-targeting immunotherapies as the Company believes that B7-H6 is an underappreciated target that could change the paradigm of cell therapy due to its broad expression in a large variety of cancers.
Celyad Oncology is of the opinion that it will potentially create more shareholder value by licensing its patent estate and further strengthening its research efforts to improve the differentiated nature of its platforms.

Based on a strategic and financial review, the Company has decided to discontinue the development of its remaining clinical program CYAD-211 (the allogeneic shRNA-based, anti-BCMA CAR T candidate for relapsed or refractory multiple myeloma (r/r MM)). There were no safety concerns leading to this decision and all patients previously treated with CYAD-211 will continue to receive their protocol-defined follow-up.

The key data points of the program are as follows:

19 r/r MM patients have been treated with CYAD-211 in the IMMUNICY-1 trial which was developed to validate shRNA technology in the clinic;
The observed safety profile, including the lack of observed Graft-versus-Host disease, provides proof-of-concept for the use of shRNA technology for allogeneic CAR Ts;
Out of 17 evaluable patients, a partial response was achieved in five patients. One patient was recently re-treated with a second dose of CYAD-211 after having reached stable disease post first infusion; and
Enhanced lymphodepletion did not seem to improve clinical activity nor persistence of the cells post-infusion.
Anticipated milestones for 2023

The Company will take part in several conferences including The World Oncology Cell Therapy Congress in April and the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 38th Annual Meeting in November; and
The Company will provide updates on the potential proof-of-concept of the dual CAR and multiplexing research programs and on business development in the second quarter of 2023.

On December 21, 2022 Anocca, a fully integrated cell therapy biotechnology company, reported that it has secured EUR 25 million Venture Debt financing from the European Investment Bank (EIB) (Press release, Anocca, DEC 21, 2022, View Source [SID1234625469]). This significant investment recognises the strength and high potential of Anocca and its transformational approach to developing T-cell therapies for cancer.

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Anocca’s CEO and co-founder Reagan Jarvis said, "We’re delighted that the EIB has chosen to support us as we build a critical piece of advanced biotechnology capability and infrastructure in Sweden. Anocca’s mission is to expand the clinical and commercial reach of cell therapies by leveraging our proprietary analytical and manufacturing platforms. This financing supports us in moving our first generation of T-cell immunotherapies towards clinical trials in a solid tumour indication during 2024."

Anocca’s Board Chairman, Hans Stråberg added, "This financing further validates Anocca’s cutting-edge and novel approach to immunotherapy. It supports our ambitious plan to create an extensive clinical pipeline of game changing cancer therapies. We welcome the EIB to our committed group of investors as we continue building a leading European biotechnology company with the potential to transform the treatment of serious diseases."

Paolo Gentiloni, European Commissioner for Economy, said: "This agreement is one of the first InvestEU investment in Sweden in life science. It is also an important contribution to the development of cutting-edge technologies which can help us fight cancer, in line with Europe’s Beating Cancer Plan. Research and development endeavours need significant and sustained investment to make sure they deliver on the promises they hold for our future. InvestEU is helping build this bright future by giving innovative companies access to the finance they need to grow and continue to innovate."

Thomas Östros, Vice-President at EIB, said: "Impressed by the team and their pioneering approach to engineering T-Cell therapies for cancer, I am delighted to announce this EUR 25 million EIB venture debt support to Swedish biotechnology company Anocca. Ultimately, our financing will help to accelerate clinical development to provide patients with access to innovative therapies in areas of high unmet medical need. This support confirms EIB’s role as a leading investor in innovation and life sciences and boosts Europe’s competitiveness and role as a research powerhouse."

On December 20, 2022 Integra Therapeutics reported the public-private consortium made up of Integra Therapeutics, Pompeu Fabra University (UPF) and the Josep Carreras Leukaemia Research Institute (IJC) has received a grant of €1,230,732 from the Spanish State Research Agency (AEI) to develop new genetic engineering technology for a CAR-T therapy to treat T-cell acute lymphoblastic leukaemia (T-ALL) (Press release, Integra Therapeutics, DEC 20, 2022, View Source [SID1234654532]).

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The funds are a competitive grant through the 2021 State Programme to Promote Scientific-Technical Research and its Transfer (formerly known as Retos Colaboración).

Integra Therapeutics will lead the project, lasting until 2025, which will use its FiCAT gene-writing platform to build next-generation CAR-T immunotherapy for T-ALL that can be silenced if any adverse effects arise, and has increased efficacy in targeting cancer cells, preventing relapses.

From the UPF and IJC, the science teams involved will be the Translational Synthetic Biology Lab led by Dr Marc Güell and the Stem Cell Biology, Developmental Leukaemia and Immunotherapy Lab led by Dr Pablo Menéndez.

T-ALL is an aggressive tumour caused by out-of-control growth of the cells that produce T-lymphocytes, and makes up 10-15% of all cases of acute lymphoblastic leukaemia in children and 25% of those in adults. Treatment with chemotherapy has improved patients’ prognosis, but the high relapse rate makes it urgent to develop safer, more effective advanced therapies that eliminate leukaemia-initiating cells (LIC), which are also responsible for relapse. In addition to chemotherapy, this project aims to improve the CAR-T therapy used in the clinic today that has improved the treatment options for many of these patients.

Integra Therapeutics has also recently been awarded a Eurostars grant for €1 million from the European Commission.

On December 20, 2022 iOnctura BV, a clinical-stage biotech developing novel cancer therapies, reported that it has been granted EUR17.5 million funding from the European Investment Council’s (EIC) Accelerator Program to develop IOA-289 for pancreatic cancer (Press release, iOnctura, DEC 20, 2022, View Source [SID1234640234]). The EIC’s funding consists of a grant of EUR2.5 million, and EUR15 million of equity investment.

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On 8 December 2022 iOnctura announced the first patient was dosed in a Phase Ib clinical trial of IOA-289 in metastatic pancreatic cancer.

Catherine Pickering, Chief Executive Officer of iOnctura, said: "We are delighted to announce this funding from the EIC to support the clinical development of IOA-289 for the treatment of pancreatic cancer. Pancreatic cancer is the only cancer with mortality on the rise in both sexes and is currently the 3rd largest cause of death by cancer in the US, and the 4th in Europe."

"There’s an urgent need to develop new therapies for pancreatic cancer and preclinical data demonstrate that IOA-289 offers a new approach, through a multi-pronged mechanism that addresses three hallmarks of cancer: fibrosis, immune suppression and tumor cell proliferation."

iOnctura was granted the maximum allowed funding in appreciation of the significant potential of IOA-289, a highly-selective, first-in-class autotaxin inhibitor, to transform the treatment of pancreatic cancer. The judging panel recognized its unique ability to simultaneously target independent tumor survival pathways associated with tumor proliferation, fibrosis and immune suppression.

Funding came as part of the most recent tranche of grants from the EIC Accelerator program under Horizon Europe, that aims to accelerate deep tech start-ups through grants and equity investments. For this second wave of grants, the European Commission selected 78 innovative start-ups for funding during a highly competitive process. In all, 240 companies were interviewed by juries of experienced investors and entrepreneurs out of a total of more than 1,000 applications. The selected companies will together receive up to EUR470 million of funding in a combination of grants and equity investments.

The Phase Ib AION-02 study (NCT05586516) is a dose-escalation study of IOA-289 in combination with standard-of-care gemcitabine/nab-paclitaxel chemotherapy in first-line metastatic pancreatic cancer.

On December 20, 2022 Erasca, Inc. (Nasdaq: ERAS), a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers, reported dosing of the first patient in the HERKULES-1 Phase 1b trial evaluating ERK1/2 inhibitor ERAS-007 in combination with SHP2 inhibitor ERAS-601 (together, Erasca’s first MAPKlamp) in patients with RAS/MAPK pathway-altered solid tumors (Press release, Erasca, DEC 20, 2022, View Source [SID1234639362]).

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"We are pleased with our team’s efficient execution that resulted in dosing the first patient in our MAPKlamp trial in 2022 ahead of schedule," said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. "ERK and SHP2 inhibition with ERAS-007 and ERAS-601 targets critical downstream and upstream nodes in the RAS/MAPK pathway, offering a rational approach that is supported by early clinical data that we presented at our R&D Day in September. Notably, we reported four responses in nine patients with BRAF-driven tumors to either monotherapy ERAS-007 or ERAS-601. Three of these responses were in tumors with BRAF Class 2 or 3 alterations, including a confirmed response to monotherapy SHP2 inhibition in a patient with a BRAF Class 3 alteration, which is dependent on upstream receptor tyrosine kinase (RTK) activation. We look forward to exploring the potential to address the high unmet need in these BRAF subtypes, which have no approved targeted therapies and represent up to 25% of all BRAF-driven tumors."

The MAPKlamp portion of HERKULES-1 will initially examine the safety, tolerability, and preliminary efficacy of ERAS-007 in combination with ERAS-601 in patients with RAS/MAPK pathway-altered solid tumors. After a recommended dose is determined, the Phase 2 expansion portion will further evaluate the safety and efficacy of the combination in patients with different mutational subtypes, including BRAF Class 2 and 3 patients. ERAS-007 and ERAS-601 had favorable monotherapy safety and tolerability profiles with largely non-overlapping treatment-related adverse events that support combination development. Forty-four percent (4/9) of patients with BRAF-driven tumors responded (one confirmed and three unconfirmed PRs) to single agent ERAS-007 or ERAS-601, including three (one confirmed and two unconfirmed PRs) in tumors with BRAF Class 2 and 3 alterations.

The clinical data referred to above was presented at Erasca’s September 7, 2022 R&D Day, and consisted of a retrospective pooled interim analysis of monotherapy ERAS-007 and ERAS-601 data, with data cutoff dates of 11/6/20, 7/11/22, and 5/16/22 for the ASN007-101, FLAGSHP-1, and HERKULES-1 trials, respectively.

About ERAS-007
ERAS-007 is a potential best-in-class ERK1/2 inhibitor being investigated alone or in combination with different inhibitors targeting upstream nodes of the RAS/MAPK pathway as part of Erasca’s MAPKlamp strategy. The extracellular signal-regulated kinases (ERK), ERK1 and ERK2, belong to a family of serine-threonine kinases that regulate cellular signaling and comprise the terminal node of the RAS/MAPK pathway. ERAS-007 is being investigated across the series of HERKULES clinical trials that span multiple tumor types and includes both monotherapy and combinations with approved and investigational agents, such as RTK, SHP2, RAS, RAF, and/or cell cycle inhibitors. HERKULES-1 is a Phase 1b/2 clinical trial for ERAS-007 as a single agent and in combination with the SHP2 inhibitor ERAS-601 (together, Erasca’s first MAPKlamp) in advanced solid tumors. HERKULES-2 is a Phase 1b/2 master protocol clinical trial for ERAS-007 in combination with various agents in patients with non-small cell lung cancer (NSCLC). HERKULES-3 is a Phase 1b/2 master protocol clinical trial for ERAS-007 in combination with various agents in patients with gastrointestinal (GI) cancers.

About ERAS-601
ERAS-601 is a potential best-in-class oral, selective SHP2 inhibitor being investigated alone or in combination. SHP2 acts as a convergent node for receptor tyrosine kinase (RTK) signaling, relaying growth and survival signals from RTKs to intracellular signaling pathways. ERAS-601 combined with the ERK1/2 inhibitor ERAS-007 makes up Erasca’s first innovative MAPKlamp strategy. ERAS-601 is being investigated across a series of clinical trials that span multiple tumor types and include both monotherapy and combinations with approved and investigational agents. FLAGSHP-1 is a Phase 1/1b clinical trial evaluating ERAS-601 as a monotherapy in advanced solid tumors and in combination in triple wildtype (KRAS/NRAS/BRAF wildtype) CRC and human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC). HERKULES-1 is a Phase 1b/2 clinical trial that includes evaluation of ERAS-601 in combination with ERAS-007 in advanced solid tumors. HERKULES-2 is a Phase 1b/2 master protocol clinical trial that includes evaluation of ERAS-601 in combination with various agents in patients with non-small cell lung cancer (NSCLC).